ascular
Embolotherapy
MEDICAL RADIOLOGY
Diagnostic Imaging
Editors:
A. L. Baert, Leuven
K. Sartor, Heidelberg
3HRMAP
J. Golzarian • S. Sun • M. J. Sharafuddin (Eds.)
Vascular
Embolotherapy
A Comprehensive Approach
Volume 2
Oncology, Trauma, Gene Therapy,
Vascular Malformations, and Neck
With Contributions by
K. Ahrar ■ H. Alvarez ■ J. C. Chaloupka ■ M. D.Darcy ■ J. Dubois ■ J. R. Duncan ■ D. Elias ■ L. Garel
J.-F. Geschwind ■ C. B. Glaiberman ■ C. Georgiades ■ J. Golzarian ■ M. Hayakawa ■ S. Heye
S.-W. Hsu ■ M. S. Johnson ■ J. R. Kachura ■ N. M. Khilnani ■ P. Klurfen ■ P. Lasjaunias ■ S. K. Lee
E. Liapi ■ W. S. Lesley ■ D. C. Madoff ■ G. Maleux ■ F. Marshalleck ■ R. J. Min ■ A. C. Roberts
A. J. Roche ■ G. Rodesch ■ R. Salem ■ M. Sharafuddin ■ G. P. Siskin ■ S. Sun ■ K. T. Tan ■ M. Thijs
K. G. Thurston ■ R. Verma ■ L. Wibbenmeyer ■ J. J. Wong
Foreword by
A.L.Baert
i 368 Separate Illustn
4y Spring
er
Jafar Golzarian, MD
Professor of Radiology, Department of Radio
University of Iowa Hospitals and Clinics
Carver College of Medicine
200 Hawkins Drive
Iowa City, IA 52242
USA
Shiliang Sun, MD
Associate Professor of Radiology
University of Iowa Hospitals and Clinics
Carver College of Medicine
200 Hawkins Drive
Iowa City, IA 52242
USA
M. J. Sharafuddin, MD
Departments of Radiology and Surgery
University of Iowa Hospitals and Clinics
Carver College of Medicine
200 Hawkins Drive
Iowa City, IA 52242
USA
Medical Radiology ■ Diagnostic Imaging and Radiation Oncology
Series Editors: A. L. Baert ■ L. W. Brady ■ H.-P. Heilmann ■ M. Molls ■ K. Sartor
Continuation of Handbuch der medizinischen Radiologic
Iv.iitVi.lC'pi-ii],! ol Mediatl Kadiology
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*
io my parents
a wellspring of love and support without limit.
I owe you everything.
io my wonderful wife, Elham
and my children Sina and Sadra
Dr. Golzarian
To my wife, Shuzhen, and daughter, Yue
for their selfless support
lo my wife Lucy, and children Jacob and Evan
Dr. Sharafuddin
To all o
Foreword
Percutaneous image-guided treatment is now well recognized as an effective minimally
invasive treatment modality in modern medicine. Its field of application is growing
every year due to the availability of more and more sophisticated materials, tools and
devices, but also because of the technical progress in reduction of the dose of ionizing
irradiation incurred by both patient and radiologist during fluoroscopy.
Vascular embolotherapy is now one of the main forms of endovascular percutaneous
treatment of diseases of the vascular system.
The editors of the two volumes of "Vascular Embolotherapy: a Comprehensive
Approach", J. Golzarian, S. Sun and M.J. Sharafuddin, leading experts in the field, were
successful in obtaining the collaboration of many other internationally renowned inter-
ventional radiologists. I am particularly indebted to Professor Golzarian for his origi-
nal concept for these books and his relentless efforts to complete the project in good
I would like to congratulate the editors and authors on producing these well-written,
superbly illustrated and exhaustive volumes covering all aspects of vascular embolo-
therapy. The readers will find comprehensive up-to-date information as a source of
knowledge and as a guideline for their daily clinical work.
These two outstanding books will certainly meet with high interest from interven-
tional radiologists and vascular surgeons. They - and therefore their patients - will
greatly benefit from its contents. Also referring physicians may find these books very
useful to learn more about the indications, possibilities and limitations of modern vas-
cular embolotherapy
I am confident that these two volumes will encounter the same success with readers
as the previous books in this series.
Leuven Albert L. Baert
Preface
Therapeutic embolization has now become a major part of modern interventional prac-
tice, and its applications have becomean integral component of the modern multimodal-
ity management paradigms in trauma, gastrointestinal hemorrhage and oncology, and
the endovascular therapy of vascular malformations and aneurysms. The past decade
has also marked the emergence of several new indications for therapeutic embolization,
such as uterine fibroid embolization, and the widespread acceptance of embolization
therapy as an effective non-operative management modality for major hepatic, splenic
and renal injuries that once posed tremendous challenge to the trauma surgeon. Emboli-
zation therapy has also become an integral facet of the modern oncology center, offering
solid-organ chemoembolization, preoperative devascularization, hepatic growth stimu-
lation prior to resection, and direct gene therapy delivery.
Despite this remarkable growth, there are currently few references available to sum-
marize this major field in vascular interventional therapy. The purpose of our two-
volume book was to organize and present the current state of the art of embolotherapy
in a comprehensive yet manageable manner. Our goal was to provide a user-friendly,
well- illustrated, and easy- to -browse resource to enable both experts and novices in
this field to quickly derive high-yield clinically relevant information when needed. In
addition to standard applications of embolotherapy, we have also included a number
of closely relakvi applications that have become intimately associated with the field of
therapeutic embolization, such as stent- graft placement and radiofrequency ablation.
The two volumes constitute the combined experience of many of the leading experts in
the field and have been generously supplemented with helpful tables, illustrations and
detailed imaging material. We have also striven to include insightful discussions and a
"cookbook" segment in each topic to provide a quick outline of procedural preparation
and technique. We have included a chapter on monitoring and resuscitation of the hem-
orrhaging patient that should be a "must-read" for the interventionist who is not well
versed in surgical critical care. Readers will also find important coverage of pathophysi-
ology and of diagnostic clinical as well as imaging workup.
We hope this reference will meet the needs of physicians providing therapeutic embo-
lization, whether they are trainees, recent graduates or even well-established interven-
tionists who wish to refresh their memory or learn the opinion of some of the field's
renowned experts before embarking on a difficult case or trying a new technique or
Iowa City Jafar Golzarian
Shiliang Sun
Melhem I.Sharafuddin
Contents
Vascular Malformation
1 Percutaneous Management of Hemangiomas and Vascular Malfor mat ic
Francis Marshalleck and Matthew S. foi
2 Predominantly Venous Malformation
Josee Dubois
Trauma and Iatrogenic Lesions 33
3 Recognition and Treatment of Medical Emergencies in the Trauma Patient
Lucy Wibbenmeyer and Melhem J. Sharafuddin 35
Visceral and Abdominal Solid Organ Trauma
Gary Siskin and [afar Golzarian
Embolization and Pelvic Trauma
Jeffrey J. Wong and Anne C. Roberts . .
Postcatheterization Femoral Artery Injuries
Geert Maleux, Sam Heye, and Maria Thijs . ,
Iatrogenic Lesions
Michael Darcy. . .
Visceral Aneurysm
8 Embolization of Visceral Arterial Aneurysms
Craig B. Glaiberman and D.Michael D. Darcy .
Venous Ablation 117
9 Endovenous Thermal Ablation of Incompetent Truncal Veins in Patients with
Superficial Venous Insulrieienv
Neil M. Khilnani and Robert J. Min 119
Embolo therapy Applications in Oncology .
10 Chemo-Embolization for Liver
Christos Georgiades and Jean Francois Gesc
XII Contents
11 Radioactive Microspheres for the Treatment of HCC
Christos Georgiades, Riad Salem, and Jean-Francois Geschwind 141
12 Yttrium-90 Radioembolization for the Treatment of Liver Metastases
Riad Salem, Kenneth G.Thurston, and [ean-Francois Geschwind 149
13 Portal Vein Embolization
Alain J. Roche and Dominique Elias 163
14 Embolotherapy for Neuroendocrine Tumor Hepatic Metastases
Kong Teng Tan and John R.Kachura 177
1 5 Bone Metastases from Renal Cell Carcinoma: Preoperative Embolization
Shiliang Sun 189
16 Embolotherapy for Organ Ablation
David C. Madoff, Rajiv Verm a, and Kamran Ahrar 201
17 Research and Future Directions in Oncology Embolotherapy
Eleni Liapi and Jean-Francois H. Geschwind 221
External Carotid 233
18 Technical and Anatomical Considerations of the External Carotid System
Paula Klurfan and Seon Kyu Lee 235
19 Endovascular Management for Head and Neck Tumors
Paula Klurfan and Seon-Kyu Lee 247
20 Embolization oi Hpiiaxis
Georges Rodesch, Hortensi a Alvarez, and Pierre Lasjaunias 257
21 Diagnosis and EndoYasail.ir Surgical Management of Carotid
Blowout Syndrome
John C.Chaloupka, Walter S. Lesley, Minako Hayakawa,
and Shih-Wei Hsu 271
Gene Therapy and Pediatri
22 Embolotlu-rapv Applications in Gene Therapy
James R.Duncan
23 Embolotherapy in Pediatrics
Josee Dubois and Laurent Garel .
Subject Index 321
List of Contributors 331
Contents and List of Contributors of Volume 1 335
Vascular Malformation
Percutaneous Management of Hemangiomas
and Vascular Malformations
Classification 3
Hemangioma 4
Clinical Presentation 4
I i iagr.ostic Imaging 4
i Treatment 5
Kaposiform Hemangioendothelioma 5
Hep.iiic Hemai:[ :•<:*. iKhehoma 7
Vascular Malfo-maluins .1
Arteriovenous Malformations S
Clinical Presentation S
! ^agnostic Imaging 9
■ Treatment 10
Arteriovenous Fistulae 11
Treatment 12
venous Malformations 12
Lymphatic Malformations 12
Clinical Presentation 12
I 'iagnostic Imaging 13
i Treatment 13
Capillary Malformations 16
Complications of Embolization
ja.7. Sclerotherapy 16
Preprocedural Preparation 16'
Post-Procedural Care and Fo!low-Up 16
Conclusion 17
References J S
Classification
Vascular birthmarks have intrigued physi
centuries. Many attempts have been madt
sify vascular birthmarks, resulting in much con-
fusion. Historically, various classifications have
been developed, each with its own shortcomings.
Initially, classifications were largely descriptive [1],
F. Marsh alleck, MD
Assistant Professor or' K.; ■.:.,:■ I ogy, Indiana University School of
Medicine, Indiana University Hospital, Room 0279, 550 North
University Boulevard, Indianapolis, IN 26202, USA
M. Johnson, MD
Associate Professor of Radiology, Director, Section of Inter-
ventional Radiology. Indiana University Hospital, UH0279,
Department of Radiology, 550 "o'niversily Boulevard, India-
napolis, IN 46202-5253, USA
Although the descriptive classification allowed dif-
ferentiation between benign and more serious forms
of vascular malformations, because many different
malformations can have similar external appear-
ances, it was limited in its value in differentiating
between them. The histopathological classification
[1] represented an improvement in the attempt to
classify vascular malformations. Its broad use of
the word "hemangioma" and lack of clinical cor-
relation limited its usefulness because hemangio-
mas and vascular maltorin.it ions Jitter in pathology
and are treated differently. The embryological clas-
sification [1] was based on the theory that vascular
malformations were due to improper development
of various cellular lines (arteries, veins, capillaries,
and lymphatics). Although the premise was sound,
the embryological classification was not clinically
useful to direct treatment. To date, the most perti-
nent classification of vascular birthmarks has been
published by John Mulliken and Julie Glowaki
[1-3]. This biological classification separates vas-
cular birthmarks into hemangiomas (vascular
tumors) and vascular malformations (malformed
vessels) (Table 1.1). Hemangiomas are characterized
by a proliferating phase and subsequent involution
phase, distinguishing them from vascular malfor-
mations which do not spontaneously involute. Vas-
cular malformations may be high-flow lesions (e.g.
arteriovenous malformations, arteriovenous fistu-
lae) or low-flow lesions (e.g. venous malformations,
capillary malformations, lymphatic malformations,
combined or mixed lesions). Vascular malforma-
tions are best managed by a vascular anomalies
team in a facility equipped and experienced in the
management of vascular anomalies. Such avascular
tionalist, dermatologist, plastic surgeon, orthope-
dic surgeon and/or neurosurgeon, pediatrician, and
physiotherapist. The percutaneous management of
these lesions including clinical diagnosis, radiologi-
cal diagnosis, percutaneous treatment (emboliza-
tion, sclerotherapy) and post-procedure care will be
F. Marshalleck and M. Johnson
HcnitiiigiC'triiii
PiV'lirer.'.ting
\::v- ■|i.:ii:'.;_'
Vascular malfc
High-flow
Arteric
venous malformations
Arteric
venous fistulae
Low-flow
Venout
malformations
Lymph
atic malformations
Capilla
ry malformations
Mixed
m alter mitt ions
1.1.1
Hemangioma
A hemangioma is a benign vascular endothelial
cell neoplasm characterized by a period of intense
cellular and endothelial proliferation resulting in
the formation of a cellular mass. During the pro-
liferation phase, there is formation of new feeding
and draining vessels similar to that of a high-flow
vascular malformation. Proliferation is followed by
involution and finally regression. This distinguishes
a hemangioma from a vascular malformation.
:al Presentatioi
Unlike vascular maltoniialions, hemangi'
commonly present at birth but u su ally be.
during the first month of life. They are m
in Caucasians, females, and premature infants and
have a predilection for the head and neck. Hemangio-
mas are the most common tumor of infancy with a
reported incidence of 10%-12% [4, 5].
A hemangioma^ location determines its presen-
tation. When it is superficial, it typically presents
as a small red macule or patch which proliferates at
a rapid rate during the first 6-12 months of life. A
superficial lesion may produce a mass (a "strawberry"
lesion) which can grow so large as to become disfig-
uring. The strawberry appearance is produced by
the presence of multiple reddened superficial vessels
which result in an irregular raised "pebbly" surface
([4]Fig. 1.1). When the hemangioma is deeper in loca-
tion, the overlying skin may in fact be normal in color
or may show bluish discoloration. The mass is usually
warm and may be pulsatile during the proliferative
phase. After the first 12 months of life, the majority
of hemangiomas undergo an involution phase which
Fig 1.1. Typical "str.;\vbe:ry" heauagiciv.Li. |[m
through the courtesy of Dr. Phillip John, MD ]
can last more than 5 years. Complete resolution of
hemangiomas occurs in greater than 50% of children
by age 5 years and in over 70% by the age of 7 years
[I]. As the hemangioma involutes, it softens, shrinks,
loses its red color and becomes dull grey due to its
replacement with fibrofatty tissue. Depending on the
original size of the hemangioma, the overlying skin
may become loose with a "crepe paper" -like appear-
ance. Occasionally, scars ortelangiectasias are seen at
the site of an involuted hemangioma [■■!].
Complications of hemangiomas usually occur
during the first o months of lite. The most common
complication is ulceration, which occurs in up to
10% of patients, especially when the lips or genital
areas are involved [1, 4]. Occasionally, there may be
associated bleeding, which is usually not significant.
Hemangiomas may also result in congestive cardiac
failure (e.g. hepatic hemangioendotheliomas) or
platelet consumption (Kasabach-Merritt phenom-
enon). Both entities will be discussed later in this
chapter. When diffuse, hemangiomas may compro-
mise the airway, obstruct vision, or impair hearing
[1]. Associated osseous deformities are uncommon
[1]. Rarely, hemangiomas may be associated with
other anomalies, such as posterior fossa malforma-
tions, right aortic arch, coarctation of the aorta, gen-
itourinary anomalies, and spinal dysraphism [6].
1.1.1.2
Diagnostic Imaging
>, when superficial, are easily diag-
lly as previously discussed. Appro-
priate treatment of a symptomatic hemangioma,
Hemangi
nosed cl.
Cerent.! neon:. Minaprine nl of Hem.iisgiomjs .m.". Vascular M..i liV-iiii:":! .-.:■:
however, requires delineation of its extent. Diag-
nostic imaging is also useful when the diagnosis
is in doubt. On CT and MR imaging, hemangio-
mas are well-circumscribed lobulated masses that
demonstrate intense parenchymal enhancement fol-
lowing the administration of intravenous contrast
(Fig. 1.2a,b). During the proliferating phase, dilated
vessels representing feeding arteries and draining
veins are seen. MR is the optimal modality for the
diagnosis and evaluation of hemangiomas [5]. The
vessels are seen as flow voids on Tl- and T2 (spin
echo) -weigh ted MR images. A proliferating hem-
angioma is hypointense to muscle on Tl-weighted
images and hyperintense on T2-weighted images.
During involution, there may be a preponderance
of fat (high signal on Tl-weighted images} with
lack of flow voids. If a lesion lacks the classic clini-
cal and imaging findings already discussed for a
hemangioma, then a biopsy should be performed to
exclude other potentially more serious tumors such
as rhabdomyosarcoma, infantile fibrosarcoma, or
neurofibroma.
1.1.1.3
Treatment
About 75% of hemangiomas will regress on their own
without treatment [1, 4]. Multiple factors will deter-
tnine whether ,i hemangioma requites treatment,
including the child's age and emotional needs, the
location of the lesion, and symptomatology. When
hemangiomas are small or are already decreasing in
size before the child enters school, observation and
reassurance are all that is needed. When treatment
is deemed necessary, systemic corticosteroids have
been the therapeutic mainstay, with a nearly 90%
response [8]. Side effects of systemic steroids include
gastrointestinal symptoms, weight gain, hyperten-
sion, immunosuppression, and growth retardation
[7-9]. Intralesional corticosteroids have been used
to treat rapidly growing hemangiomas with the dose
limited by the size of the hemangioma [7-9]. When
steroids fail to cause adequate response, alpha inter-
feron, chemotherapeutic agents, and radiotherapy
have also been used [10-12]. The use of a- interferon
is now limited to refractory cases due to its effects on
the central nervous system such as spastic diplegia
[13]. Laser therapy has been used to treat areas of
ulceration, bleeding, telangiectasias, and skin dis-
coloration [14].
Surgical removal becomes warranted in cases of
ocular hemangioma unresponsive to medical ther-
Fig 1.2a,b. Proliferating hemangioma of the ringer demon-
strating: a low siga.il on Tl -iveielileJ image and b intense
parenchymal enhancement with gadolinium
apy and for airway compromise. Cosmetic needs may
dictate surgical removal depending on the parents'
and patient's wishes especially for head and neck
hemangiomas. After involution, surgical resection
may be required to remove excess skin and fibro-
fatty tissue [4]. In the minority of cases in which a
hemangioma fails to involute (non involuting hem-
angioma) despite medical management, surgical
resection of the lesion, if possible, is indicated [15].
Percutaneous embolization prior to surgical resec-
tion has also been successful [16].
Rarely, arterial embolization is required to treat
life-threatening hemorrhage, high-output cardiac
failure, or platelet consumption (Kasabach-Merrift
phenomenon) ([17], Fig. 1.3a-c).
1.1.2
Kaposiform Hemangioendothelioma
Kaposiform hemangioendothelioma is an infil-
trative variant of pediatric hemangioma. It com-
monly affects the trunk and extremities, produc-
ing an edematous mass of variable size with purple
skin discoloration (Fig.l.4a,b). It proliferates and
involutes like a typical hemangioma but persists,
infiltrates, and consumes platelets (Kasabach-Mer-
ritt phenomenon) resulting in hemorrhage [18, 19].
Rarely, it may resemble a classic hemangioma [20].
Platelets decrease to low levels (< 5000) despite
repeated transfusions. Management involves a
multidiscipli nan approach [21]. Chemotherapy, ste-
F. M..irsh..illeckand M.John;
bach-Merritt ]
parenchymal ■
c Angiographi
Tia of the trunk resuming .11 K.-Sji-
n. b CT miner ■Jemonr.iTitii'.ii
it with contrast aJnumstrjiiun.
j demons! fa ;ing multiple enlarged
emboli zed with PV'A p.'.rticles prior
Fig 1.4. a Kaposi form HeiiiiinHioeiiJoLieliomj p resen I mi:
findings in the sjiiis pniieiil deT.cnsrr.'.tmg .1 diffuse piirendr
Dr. Phillip John, MD)
!- : ei"ciit.':[iC'jLi; : Maaagerr.ent of He:
■s an;: Vascular Malformatio:
roids, ct-interteron, and radiation have all been tried
[22, 23]. Surgical resection can be curative [24] but,
in many cases, may not be possible due to the risk of
hemorrhage. ] ntervenlional management comprises
treatment of the associated platelet consumption by
endovascular embolization using a microcatheter
technique. PVA (polyvinyl alcohol) particles and/or
absolute alcohol are typically used [25-27]. These
cases are usually difficult to treat and time-con-
suming due to the presence of multiple feeders. The
long-term effects of endovascular embolization have
not yet been established.
1.1.3
Hepatic Hemangioendothelioma
Hepatic hemangioendothelioma (multiple hepatic
hemangiomas, congenital hepatic hemangioma) of
the newborn is characterized by a liver mass, an audi-
ble bruit, and congestive heart failure with or without
cutaneous heman^iomata ([]], l-'ii:. 1.5a- cj. The hish-
output cardiac state could be fatal. Hirst-line manage-
ment is medical with the use of steroids, interferon,
or chemotherapy. Endovascular embolization can be
performed as a temporizing measure to liver trans-
plantation if surgical treatment (hepatic resection,
hepatic artery ligation) is not possible and if medi-
cal therapy fails [28], The vascular anatomy may be
complex with multiple collaterals and various shunts
(arteriovenous, arterioportal, portovenous) resulting
in the high-output state [29, 30]. In order to treat the
severe AV shunting in the liver, endovascular embo-
lization can be performed. Selective hepatic arterial
embolization has been used to treat arteriovenous
shunts. Coils [31, 32], detachable balloons [47], and
PVA particles [33] have been used. Coils and detach-
able balloons result in permanent occlusion and their
use depends on personal preference. The hepatic
artery canbe accessed via I lie femoral artery, a central
vein, or femoral vein by '.vay ot a patent foramen ovale
[32] or via a patent ductus arteriosus in neonates [34],
In cases of portovenous shunts, the portal vein can
be accessed using a transjugular approach, transhe-
patic approach or via the umbilical vein in neonates
[34] to allow for coil embolization. In cases where
portovenous shunts are dominant, hepatic arterial
embolization alone may not prove to be of benefit
Fig 1.5, ii C".' so:;:; image in a newb'.'ra . : . eni-.jj";SL:":i: ij:g !ir.\
.y.bCT arterial phase cenr 'ii : a:a:iiig :::ul;iple hypo J,
fs Kidiiii the liver, c CT port.-! venous phase
lultiple masses with nodular enhancement
h M.ir>h.iU.:k -mi V. !■
and may result in hepatic necrosis [30, 35]. It is there-
fore imperative to perform an angiographic study to
include the portal venous circulation and potential
collateral vessels to allow for careful planning before
embolization is performed [29].
Vascular Malformations
Vascular malformations, unlike hemangiomas,
are not neoplasms, but instead represent errors
of vascular morphogenesis resulting in abnormal
blood vessels and lymphatics [!]. They are classified
into high-flow and low-flow lesions based on their
hemodynamic properties. High-flow lesions include
arteriovenous malformations (AVMs) and arterio-
venous fistulae (AVFs). Low-flow lesions include
venous malformations, lymphatic malformations,
capillary malformations, and combined malforma-
tions. Vascular malformations tend to be present at
birth and grow commensurate with the growth of
the child. The majority ot vascular malformations
can be diagnosed with history and physical exami-
nation and confirmed by diagnostic imaging.
1.2.1
Arteriovenous Malformations
Arteriovenous malformations (AVMs) consist of
multiple small abnormal connections (nidi) con-
necting large arterial feeding arteries to large drain-
ing veins without an intervening capillary bed.
Clinical Presentation
AVMs affect males and females equally. Their growth
is known to be stimulated from hormonal changes
during puberty, hormonal therapy, and pregnancy
[1]. AVMs are classified into four clinical stages
according to the International Society for the Study
of Vascular Anomalies (ISSVA) Schobinger clas-
sification [36]. Stage 1 represents a dormant AVM
which present like a capillary skin stain or a small
pulsatile skin mass. In stage 2, an AVM is larger and
presents as a warm, tender, red, pulsatile mass with
visible large draining veins and an audible bruit. In
stage 3, the AVM is complicated by ulceration, bleed-
ing, and associated destructive osseous changes. In
stage 4 (2.5% of cases), the AVM results in conges-
tive cardiac failure due to increased arteriovenous
shunting. AVMs may affect the head and neck,
extremities, and viscera (e.g. lungs, liver, kidneys,
spleen, and pancreas). AVMs maybe focal, but more
frequently are diffuse and cross tissue planes. AVMs
become symptomatic when they bleed, ulcerate, or
exhibit mass effect on nearby structures.
In the extremities, AVMs typically present as a
soft tissue mass with hyperthermia, redness, ten-
derness, and swelling (Fig. l.oa). The draining veins
are usually visibly distended and associated with a
palpable thrill and an audible bruit. There is usu-
ally associated tissue ischemia and edema which can
lead to ulceration. It has been postulated that the
skin necrosis is due in part to arteriovenous shunt-
ing but also due to associated venous hypertension
and mass effect [1]. Ulceration can ultimately lead to
life-threatening hemorrhage and can also be compli-
cated by infection. Spontaneous bleeding is uncom-
mon in the absence of ulceration or trauma. When
intramuscular, AVMs may produce significant pain
[1]. Pelvic AVMs are rare and typically present with
pelvic pain, pedal edema, menoi rliagia, hemorrhage
(antepartum, postpartum) or a pulsatile mass on
pelvic exam. In males, dysuria, frequency, impo-
tence, tenesmus, and hematuria can occur [37-39].
AVMs may produce lytic osseous lesions or result in
limb overgrowth. Congestive heart failure can result
if the AVM is large or if it occurs in infancy.
When affecting the brain, an AVM can present
with hemorrhage, stroke, seizures, or focal neuro-
logical deficits. Spinal AVMs present with hemor-
rhage or a myeloradiculopathy. Dental AVMs can
present with life-threatening hemorrhage after tooth
extraction, eruption, or infection [1].
AVMs of the abdominal viscera are uncommon,
but when they do occur, they have an increased prob-
ability of bleeding due to the proximity to mucosa.
True AVMs of the liver in the newborn will present
with a clinical picture similar to hepatic hemangioen-
dothelioma already discussed. Pancreatic AVMs [40,
41] are usually associated with Osier-Weber- Rendu
syndrome. Splenic vascular malformations are usu-
ally asymptomatic and found incidentally at autopsy.
They can also present with splenomegaly, pain, bleed-
ing, portal hypertension, and hypersplenism [42].
Vascular malformations of the kidney are rare.
Pulmonary AVMs can occur sporadically (15%) or
as part of the autosomal dominant disorder (60%-
90%) known as Osler-Weber-Rendu syndrome or
Hereditary Hemorrhagic Telangiectasia (an autoso-
mal dominant disease characterized by telangiecta-
Perciitaneon:. Ma:'.a£e:''.eiil of Hemangiomas ..in.:. V'ascinar M..i liV-iiii:":! .-.:■:
Fig US. a AVM of the left hand (hypothenar eminence) with
distended, palpable and pinsatite vessels. The light hand is
shown for compaiiso::. lv Angiographic evaluation dem-
onstrating a la:ge nidus involving t:ie :".ypoihenai" eminence
with enlarge;", feeding vessel 1 ; a nil draai.ng veins. d,e Angio-
graphic images de:v..: iistiai.ng microcadierer snpeise lectio:'
of the nidus by different feeders to a'lovy for alcohol enibo-
sias, recurrent epistaxis, and a family history of tel-
angiectasia). Pulmonary AVMs are multiple in up to
55%, bilateral in 40%, and occur mainly in the lower
lobes. The AVMs are usually simple with a single
feeding artery (80%) but may be complex with mul-
tiple feeding arteries (20%). Patients present with
symptoms of hvpoxia due to arteriovenous shunting
(e.g. dyspnea and cyanosis), paradoxical emboliza-
tion resulting in CVA, TIA, or brain abscess and/or
congestive heart failure [50, 51].
1.2.1.2
Diagnostic Imaging
The characteristic imaging find ings of AVMs include
dilated feeding arteries and dm mi tit; veins. On CT
i enhance after the adrr.
contrast while on MR imaging
the vessels are seen as multiple prominent flow voids
onTl-and T2 -weighted spin echo sequences [5]. The
vessels will be bright on gradient echo sequences.
Unlike a hemangioma, there is no parenchymal
mass and the nidus is usually not visible. Various
signal changes indicative of blood products may
be seen if the AVM has bled. Associated soft tissue
(edema) and bony changes may also be seen. History
and physical examination will usually suffice in the
diagnosis of AVMs affecting the extremities with
imaging performed to document the extent of the
lesion. CT imaging is superior to MR in the delin-
eation of pulmonary AVMs. Visceral lesions may
be investigated with CT and MR imaging. Angiog-
raphy is usually not required for diagnosis, but is
F. M..irsholk>ckand M.John;
performed for treatment planning, at the time of
percutaneous embolization, or if the diagnosis is in
doubt. Angiography is superior to delineate the nidi
and also clearly demonstrates the large feeding ves-
sels and early draining veins (Fig. 1.6b,c).
1.2.1.3
Treatment
The vast majority of AVMs will cross surgical planes
to involve the deep tissues, making surgical resec-
tion impossible due to the risk o] siijnihcani hemor-
rhage or of damage to associated tissues or organs.
Excisional surgery becomes more feasible after suc-
cessful embolization. Percutaneous management of
AVMs is difficult, with complete lasting obliteration
of the AVM usually not possible even with current
techniques. Percutaneous treatment is performed
mainly to control symptoms such as pain, distal
ischemia leading to ulceration, hemorrhage, and
congestive cardiac failure [5]. Amputation may be
the necessary end result in cases of extensive AVM
of the extremity when embolization fails to control
the symptoms [43].
For those patients where treatment is ind tented,
an initial diagnostic arteriogram is performed.
Although treatment of the lesion might be per-
formed at that time, the diagnostic and therapeutic
procedures may be performed separately, to mini-
mize contrast volume and to ensure that appropriate
equipment is available. In young children, the pro-
cedures might be combined to decrease the number
of times the patient needs to be placed under general
anesthesia. Superselective arterial embolization is
usually performed using microcatheter techniques.
The aim is to selectively embolize the feeders to
the nidus without compromising blood supply to
essential nearby structures. This often proves to be
difficult and time-consuming because the major-
ity of AVMs will have numerous feeding arteries
and draining veins. Occluding a feeding vessel too
proximally will only lead to development of new
feeders and is thus ineffective. This will ultimately
lead to recurrence and distal ischemia as new ves-
sels are recruited [44]. Additionally, proximal occlu-
sion may make subsequent attempts at embolization
more difficult.
In order to attempt embolization of the nidus
within an AVM, various agents such as PVA par-
ticles, absolute alcohol, and tissue adhesives (glue)
have been used. PVA particles are available in sizes
ranging from 50 um to 1000 (im. They are useful
when multiple micro fistulous connections exist
within the nidus. The size of the particles must be
larger than the connections to avoid escape into the
venous system. The effects of PVA particles are usu-
ally temporary with a high rate of recurrence due
to subsequent development of collaterals compro-
mising future percutaneous management [44]. PVA
particles are therefore best suited for preoperative
embolization to minimize bleeding during surgical
resection [45].
Absolute alcohol is a very effective embolization
agent because it destroys the walls of the blood ves-
sels by inciting a strong inflammatory reaction. In
order to maximize the effect on AVMs and simulta-
neously prevent effects on vital structures, alcohol
is delivered directly into the nidus by superselec-
tive catheterization or via direct puncture ([47,48],
Fig. 1.6d,e). Occluding inflow arteries or outflow
veins maximizes the effect on the nidus. The objec-
tive is to confine the injected alcohol within the
nidus. Inflow occlusion can be achieved with the
use of balloon catheters. If inflow occlusion is not
possible, then outflow occlusion can be achieved
with the use of orthopedic tourniquets, blood pres-
sure cuffs (inflated to supra systolic pressures}, or
manual compression depending on the location of
the lesion [44]. Contrast is injected into the nidus
during inflow occlusion until the draining veins
are seen. This reflects the volume of alcohol needed
to fill the nidus without spilling into the draining
veins. Follow ing emit i tit us ton of alcohol (retained
for several minutes within the lesion prior to releas-
ing the inflow or outflow obstruction), contrast
injection should be repeated to follow the effects
of alcohol, with stasis within the nidus being the
ultimate goal. Some authors have advocated that
alcohol should be the only agent used in the treat-
ment of AVMs and that alcohol therapy can be
curative [44]. While we agree, it is important to
consider the risk of necrosis of nearby vital tissues
and of the skin need to be considered when alcohol
is administered by a percutaneous or endovascular
route. Also, the risk of systemic toxicity increases
in doses above 1 ml/kg or if a volume greater than
60 ml is used. Complications can be as high as 15%
of patients treated with absolute alcohol [44]. Most
complications are self-limiting or may be success-
fully treated (e.g., with skin grafting in the case of
skin necrosis); however, neurologic complications
can be permanent. Some au thors advocate that gen-
eral anesthesia should be used when embolization
will be carried out using alcohol, due to its possible
local and systemic effects [25]. We agree that gen-
Percutaneous Mar.aeriy.eiil of Heni.ing.omas an.". Vvi:cul.ii Malformations
eral anesthesia should be used in children when
embolization is performed with absolute alcohol.
In adults, by keeping the patient awake with con-
scious sedation, the local effects of absolute alcohol
can be assessed clinically (e.g. assessing for neu-
ropathy in the extremities during absolute alcohol
therapy).
Tissue adhesives work by forming a cast within
a blood vessel resulting in occlusion. It is available
as an injectable liquid that immediately polymer-
izes when it contacts ionic fluids such as blood. It
can also be diluted or modified to polymerize after
variable periods. Tissue adhesives are of value in
the treatment of very hiab-ilo'.v AVMs '.vliere ins ton!
polymerization is advantageous to avoid entry
into the draining veins. The disadvantage of tissue
adhesives is that, unlike absolute alcohol, they may
not totally destroy the nidus resulting in eventual
recanalization. Coils and detachable balloons pro-
duce too proximal an embolization and should be
avoided in the treatment of extremity AVMs unless
the arteriovenous connections are quite large and
glue is unavailable [46]. When a transarterial route
to the nidus is not possible, the nidus can be directly
injected with absolute alcohol or glue [47, 48] or
accessed via a transvenous route [44, 49].
Approximately 80% of pulmonary AVMs will
be of the simple type with a single feeding artery
making them amenable to percutaneous emboliza-
tion with coils or detachable balloons (Fig. 1.7a,b).
Cure of up to 84% ot pulmonary AVMs with a single
procedure has been reported [50-52].
Renal AVMs are rare and are typically small in
size but can be quite large. Percutaneous emboli-
zation has been documented in the treatment of
symptomatic lesions (hematuria, congestive cardiac
failure, or hypertension). Percutaneous emboliza-
tion using coils, Gelfoam, i'VA particles, and glue
(N-butyl- cyan oner via lei lias been reported [53-55],
Uterine AVMs have successfully been embolized
with PVA particle's, Gelfoam, sine, ami coils [?(■],
1.2.2
Arteriovenous Fistulae
Arteriovenous fistulas (AVFs), like AVMs, are high-
flow vascular malformations but consist of a single
macrofistulous communication between an artery
and a vein (Fig. 1.8a-c). They are not common in
childhood and are considered to be posttraumatic in
origin. They are, however, still found in the absence
of a history of trauma [26]. Like AVMs, they can
produce CHF due to arteriovenous shunting. Small
AVFs may close spontaneously and larger lesions
can enlarge over time presenting in the extremity as
a pulsatile lesion with a palpable thrill and audible
bruit. Angiography easily demonstrates the single
large interconnection. Visceral AVF are usually iat-
rogenic and can present with hemorrhage.
Fig 1.7a,b. Left pulmonary
AVM years
with HereJii.nv Hrmory.'.aeii" i'-Lnpe.a
::.:.;"'.■;':":': I !.:■!!■:. b y.ii.Yc-iviiil ■;.:■! I eiv.oo.i^cio:'. .:■[' .; neu
isi.i. a Form a: ion of ;'.rv. : p aim onarv
pulmonary AVM
F. Marshalleck and M. Johnson
1.2.2.1
Treatment
AVFs are amenable to percutaneous endovascular
embolization with coils and detachable balloons
[57-59] or ethanol [60]. The aim is to embolize the
macrofistulous connection or the immediate drain-
ing vein. When this is not possible, a stent graft or
covered stent can be percutaneously placed within
the feeding vessel to cover the AVF [61]. If the feed-
ing vessel can be sacrificed, it can be occluded using
coils, detachable balloons, or glue [26]. In occluding
large AVFs, migration of a deployed device can be
prevented with the use of balloon catheters, snares,
and tourniquets.
1.2.4
Lymphatic Malformations
Lymphatic malformations (formerly known as cystic
hygroma or lymphangiomas) are ma Id eve lop me nts
of the various components of the lymphatic system.
They are localized malformations affecting the vari-
ous layers of the subcutaneous tissue and exhibit low-
flow characteristics. They are usually multiloculated
and are divided into microcystic (cysts <2 cm in dia-
meter), macrocystk", and mixed categories.
1.2.3
Venous Malformations
The management of VMs
in the next Chapter.
1.2.4.1
Clinical Presentation
Lymphatic malformations (LMs), like other vascu-
lar malformations, are commonly present at birth
with a predilection for the head, neck and axilla
(Fig. 1.9). They affect both sexes equally. They are
less common than venous malformations and are
usually subcutaneous [1, 5, 68].
P emit. 1 , neon:. M.n'.a£r:''.ent of Heni.ing.omas .ni.". Vvi:cul.ii Mjlrormalio:
1.2.4.2
Diagnostic Imaging
MRimagingotmaaocystkLMsshowsmultipIelarge
cysts isointense Co muscle on Tl-weighted images and
hyperintense on T2-weighted images, with periph-
eral rim enhancement, septal enhancement, or no
enhancement with gadolinium (Fig. l.lOa-e). There
may be fluid-fluid levels and signal characteristics
presenting blood products (Fig. l.lla-c). Edematous
changes maybe seen in the surrounding subcutane-
ous tissue [5]. Osseous distortion and overgrowth
are best demonstrated on CT. The microcystic vari-
ety demonstrates similar characteristics; however,
the hyperintensity on T2-weighted images is more
diffuse due to the presence of microcysts. Cysts are
also readily demonstrated by ultrasound with low-
flow dynamics seen on Doppler imaging [5].
Fig 1.9. Lymph a tic malformation of the i
by Dr. Phillip John, MD)
jck. (Image provided 1 .2.4.3
Treatment
They can enlarge significantly and extend
through various tissue planes to dissect into the
mediastinum thus making surgical removal diffi-
cult. Mass effect can lead to airway compromise and
osseous overgrowth [1], LMs can occur with other
malformations such as capillary and venous malfor-
mations. The most superficial form of LM is referred
to as lymphangioma circumscriptum (LC) and con-
sists of visible thin-walled clear lymphatic vesicles
on the skin that, on occasion, exude lymph. If hem-
orrhagic, the LC may become pink in appearance.
It is seen most commonly at the shoulder, buttocks,
neck, or mouth. Optimal treatment, to control per-
sistent leakage of lymph and for cosmetic reasons, is
operative resection [1].
The classic LM presents at birth as a soft translu-
cent mass at birth that, unlike some venous malfor-
mations, cannot be manually decompressed. Also,
unlike venous malformations, LMs do not enlarge
during the Valsalva maneuver. They may be asso-
ciated with overlying lymphangioma circumscrip-
tum. When complicated by hemorrhage, the mass
becomes firm. LMs can also become secondarily
infected causing them to become tender, warm, and
erythematous [62]. They frequently enlarge during a
viral illness. When the LM is extensive and becomes
secondarily infected, the result can be airway com-
promise [63, 64]. Other complications include SVC
obstruction, chylothorax, pulmonary hypoplasia,
and death [65-67].
Treatment is indicated to relieve symptoi
pain or airway compromise or to improve c
caLly. The macrocystic form of LM responds favor-
ably to surgery and sclerotherapy with sclerotherapy
having similar success rates but less morbidity [68],
Sclerotherapy is performed using direct percutane-
ous puncture using a variety of agents, e.g. ethanol
[68], doxycycline [69-71], bleomycin [72], Ethibloc
and OK-432 [73-76]. Bleomycin, a chemotherapeutic
agent, may be used for sclerotherapy of LM, but has
systemic side effects such as pulmonary fibrosis.
OK-432 is a superantigen produced from Streptococ-
cus A and is not yet available in the USA. Ethibloc
is composed of Zein protein, contrast and ethanol
and is also not available in the USA. Doxycycline
has been used to treat microcystic LM, in neonates
where the use of alcohol is limited due to the patient's
weight and in the treatment of very large lymphatic
malformations in which a large volume of sclerosant
is needed. It is available in powder form (100 mg)
and is mixed with saline in a concentration of 10 or
20 mg/ml. Volumes up to 100 ml can be used. Doxy-
cycline produces pain during injection, is nontoxic,
and may result in only mild adverse reactions, e.g.
fever [68]. The most commonly used sclerosant for
macrocystic LM is ethanol with a maximum dose of
1 ml/kg or a maximum volume of 60 ml [5].
Depending on the size of the cysts, their contents
can be drained using single or multiple angiocath-
eters, a catheter with multiple side holes, or a pig-
F. Marshalleck and M. Johnson
Figl.lOa-e. Unilocular lymphatic in.il for in at ion involving the i
tongue demonstrating: a low density on CT, b increased signal
weighted images due to its proteinaceotis content, c high signal
weighted images, and d rim enliajwme:'/ with gadolinium ad]
e Contrast injection during sclerotherapy demonstrating a singl
tail catheter. The volume aspirated will del
the volume of sclerosant to be used. Various authors
report using a volume of sclerosant equal to 30%-
100% of the aspirated volume [70]. Contrast injec-
tion confirms the location of the needle and catheter.
The contrast is aspirated and then the sclerosant is
instilled. To minimize the use of contrast and con-
comitant potential dilution of the sclerosant, access
PerciitJiifoii:; M.n'.:]gr:''.enl of Heni.ing.omas .in.: VVi:aila< M.ilroinijiiioi
Figl.lla-c. Lynipj'.'itic uuilfo: ai.Uion aa\eno: ::■ die light parotid gland
de niois si:'Li:ing: a [liuiliple fltiid/rhiid level? on Tl MR-weighleo images,
b Tl MR-\veiglueo iinagrs and e MR nii.iges with g,idoli:in-:i5
into the cyst can be achieved using sonographic
guidance. CT can also be used to guide sclerotherapy
[69]. The sclerosant is injected with a tiny amount
of contrast with subsequent CT scanning to confirm
opacification of the cysts. Some authors will mix
the sclerosant with a small amount of contrast and
utilize fluoroscopy during injection to evaluate for
venous escape [26]. When alcohol is the sclerosant
of choice, it is instilled, leftto dwell for up to 15 min,
and then drained with subsequent needle removal.
In order to increase dwell time when doxycycline is
used, aspiration of the sclerosant is not performed.
A pressure dressing is applied to minimize leakage
iollowuig the procedure.
Sheils etal. describes a coaxial technique for large
cysts using a coaxial system consisting of a 14G angio-
catheter and 5F pigtail catheter. The cyst is accessed
with the 14F angiocatheter and the 5F pigtail catheter
is advanced through the existing angiocatheter into
the cyst. Contrast is injected to opacify the LM. After
the contrast is aspirated, l%Lidocaine is injected and
left to dwell for 10 min. After aspiration, 3% sodium
tetradecyl sulfate, a detergent sclerosant, is injected
and left to dwell for 1-2 min. After aspiration, alco-
hol is injected and left to dwell for 15 min. At each
step, 50% cyst volume is utilized. After the alcohol is
aspirated, the catheter is connected to a fackson Pratt
suction bulb system and suction is performed for up
to three days while the patient is on oral antibiotics.
Pigtail catheter drainage can be followed up with
repeated injections of the sclerosant until there is no
further drainage. Ultrasound evaluation performed
one month following sclerotherapy has shown com-
plete ablation in 95% of patients where catheter drain-
age has been used [70].
Fluid aspiration and contrast injection may not be
feasible when treating the microcystic form of LM.
Ultrasound imaging is therefore useful to monitor
the injection of microcysts. Due to the local effects
of alcohol such as tissue necrosis and nerve injury,
h M.ir~h.iU.:k -mi V. !■
doxycycline is usually the sclerosant of choi
treatment of microcysticLM [45].
1.2.5
Capillary Malformations
Capillary malformations (C.Ms), because of the:
appearance, have traditionally been referred to as
port wine stains and incorrectly as capillary heman-
giomas. They represent maldevelopment of capillar-
ies and present as well demarcated skin discoloration.
CMs initially have a pink or red color and become
more purple as children age. CMs frequently occur
with other vascular anomalies. InKlippel-Trenaunay
syndrome, they occur on the trunk or lower extrem-
ity and are associated with limb hypertrophy and
widespread venolymphatic malformations. In Sturge-
Weber syndrome, the CM is typically in the VI (first
division of the trigeminal nerve) distribution on the
face and is associated with underlying ophthalmo-
logic and leptomeningeal VMs and CMs.
Treatment options for CMs include mainly pulsed
dye laser therapy and also corticosteroids, inter-
feron, and surgery [77-79]. The interventional radi-
ologist may be called upon only to treat the associ-
ated lesions such as VM and LM in order to alleviate
Complications of Embolization
and Sclerotherapy
The
utaneous treatment of a:
nbe quite challenging. Emboliz
al-
Preprocedural Preparation
The indications for treatment are clearly delineated.
Treatment may be performed only to alleviate symp-
toms, since in many cases a cure is not possible.
The risks and benefits are clearly explained to the
patient. Lab studies are performed as in many inter-
ventional procedures to test clotting parameters and
renal function. When small toatl malformations are
treated with agents other than ethanol, the proce-
dure can be performed using conscious sedation. It
is generally recommended that when a significant
volume of alcohol is to be used in the treatment of
a large AVM, especially in patients with pre-existent
cardiac compromise, that general anesthesia is per-
formed. Pulmonary arterial pressures maybe moni-
tored. Some authors advocate hydration before the
procedure to protect the kidney from the effects of
hemolysis [68]. A Foley catheter may be inserted.
Proper equipment (sheaths, microcatheters, wires,
and embolic agents) is essential. A nti- inflammatory
medications such as corticosteroids are given just
before and continued after the procedure to mini-
mize swelling. Antibiotics (e.g. cephalexin) are usu-
ally given for 10 days after sclerotherapy of LMs due
to the risk of infection. Antiemetics, antibiotics and
analgesics may also be administered especially for
transarterial embolization cases.
format i(
can fail if the nidus cannot be reached or if the
malformation is not adequately treated. Additional
complications include embolization to distal tis-
sues or organs, thrombosis of normal vessels,
nausea/ vomiting, pain, fever, swelling, and post
embolization syndrome. Although absolute alco-
hol can be effective in the management of vascu-
lar malformations, the complication rate can be as
high as 10%-15%. Local effects of alcohol include
tissue necrosis, neuropathy, and skin ulceration.
Systemic effects include CNS depression, hypogly-
cemia, systemic hypertension, pulmonary hyper-
tension, cardiac arrhythmias, bradycardia, pulmo-
nary vasoconstriction, disseminated intravascular
coagulation due to fibrinogen consumption [80],
hemoglobinuria, pulmonary embolism, and car-
Post-Procedural Care and Foliow-Up
In addition to routine vascular postprocedural
care, several post-embolization-specific procedures
should be employed: The treated extremity should
be elevated to alleviate edema. Pain control is usually
necessary and may require intravenous narcotics: A
patient-controlled-anesthesia (PCA) pump works
very well for the majority of patients. Whenever
absolute alcohol is used, the overlying skin should be
observed for blanching or blistering, which, if pres-
ent, suggest skin injury. Mild cases can be treated
with topical antibiotics or Silvadene cream. Plastic
surgeons should be consulted early, as necrosis might
ensue, and skin grafting might be required. Neuro-
Percutaneous Manageir.enl of Heni.ing.omas jii.: Vascular Malrbrmaiioi
T.ifle 1.2. -
ia Is and equipment
IR clinic with ancillary surf (clerks, nurses, phvsi.
Portable Doppler ultrasound machine, to allow evaluation of vascular status
lar lesions
Imaging equipment and expertise: MRI/MRA, CT/CTA, US with color flow, h
5ners), and time tor p::y:
ior to and following
h-speed DSA
lary vein or artery at
ice, e.g., in the
>t be advanced thro-: eh small feed ins vessels to lesion
el appropi iaie guidewne. The transcend guidev
Cook Micropuncture sheath: A very versatile sheath which can be u
angiography and/or embolization, or, as described above, as a direc
Caih.elers
• Standard array of 4F and 5F catheters
• Hydrophilic catheters: Way be necessary if standard catheters a
• Microcatheters: The Transit catheter (Cordis) is quite useful
• Guidewires: Standard array: if microca dieter is used, will n-
a good choice
• Balloon catheters: E.g., die Cool. Over-1 he-wire Fogany bafoon caiheie:: Sue. catheters i:.)n he used as proximal occlu-
sion catheters, throng;; which microca dieters can be a. mm need, and through which alcohol (e.g.! can be infused. The use
of proximal occlusion as wi;h these devices is especially vadiaKe in Ireaiment of high -flow lesions.
Blood pressure cuffs: Pediatric, standard, and large. Siipra-ysiolic inflation of Bf- 1 cuffs can be used ■: as can direct pressure
and/or tourniquets) to prevent outflow rrom lesions to be emboli zed or sclerosed.
Embolization materials
• Absolute alcohol
• Glue
• +/- Sotradeehol (may be or" some value in dealing very sroerficial lesions, as it may be less iikeiy :c- cause skin necrosis)
• Coils: Althoug.i usually not necessarv and ustiady conlra indicated in the treat men: of AV.Yls and V'V Ms 'because coils .its:
unlikely to be successful in the treatment o: I hose lesions and ihey interfere widi subsecuenl access), coils are invaluable
in I he treatment of PAV Ms and AVFs. A wide range of coils should be available for such lesions.
• Balloons: May be necessary in ihe treatment o:' high -flow lesions
Sifvacene cream: lii ihe unfortunate evenl that a person develops s^m breakdown after a procedure, appropriate would care
Point 1: Be prepared. Ascertain that :lie pal lent and hi -/her family understand what to expect from Ihe procedure; ensure that
adequate analgesia is available: ensure lhal af necessarv equip mem ( inc.nding ultrasound I is readily available.
Point 2: 1 >o:t : lose access. Always, use a sheadi when approaching a lesion from the ins.de. Co-ax irf access :. sheath ami ca I heier,
or sheath a no catheter and microca dieter) is mandatory. Similarly although yon ciin treat a lesion widi direc: injection through
.: lire." le, :. Ilex it !e she.: I.:, e.g., ihe aF inner no it ion 01" a C. :■..■.. 41- yicropuncrare ;i :; ns. t.. :■ 11. ■. ..:na:o-r nrovi..ies oeiter srabililv.
Point 3: Be prepared for ad outcomes, both successful and otherwise: e.g., prompt discussion w.li: a plastic surgeon can be of
s benefit in patients who- develop ssin breakdown.
logic examination of the treated extremity is essential
to evaluate for neuropathy. Most peripheral malfor-
mations will visibly swell soon after treatment, reach
a peak a few days later, and subside over the next few
weeks. The degree of expansion is expected to subside
over the next two weeks. Overnight stay is indicated
if large lesions are treated especially if airway com-
pression can occur. ICU admission may be necessary
with intubation to protect the airway. In the presence
of hemoglobinuria, the urine needs to be alkalin-
ized with sodium bicarbonate to protect the kidneys
from crystallization [68]. When pigtail catheters are
placed e.g. in LMs, the patient are hospitalized for
a few days. Follow-up appointments may be made
in 4-6 weeks to evaluate response to treatment and
determine if repeat embolization or sclerosis is nec-
essary. Lesions are followed clinically and with MR
iiiuu-iii:: ns indicated.
Conclusion
As discussed, the most useful classification of vas-
cular malformations to date is the one by Mulliken
and Glowaki. The majority of vascular malforma-
tions can be diagnosed clinically with MR1 now the
gold standard to delineate the extent of the lesion or
in cases where the diagnosis is in doubt.
The majorities of hemangiomas are best left alone
and will regress either spontaneously or with medi-
cal treatment. End ova scu lar embolization can be
helpful in the cases of noninvoluting hemangiomas,
Kapositorm hemangioendotheliomas, and hepaiio
hemangioendotheliomas. This can prove to be quite
challenging. The aim is not to cure but to stabilize
deleterious effects such as hemorrhage and throm-
bocytopenia.
F. Marshalleckand M.John;
embolization of high-flow mal-
j proper planning and the use
Endo\
form at io
of microcatheter techniques. Although alcohol
may produce the best result, it should be used with
extreme caution due to its local and systemic effects.
Although a cure may not be possible, relief of symp-
toms can be achieved in the majority of patients.
Percutaneous sclerotherapy of low-flow vascular
malformations can be technically straightforward,
but requires pre-procedure and post-procedure
planning in order to avoid serious complications.
1. Mulliken ]B, Young A i [ ; 'f S: Vjslii1:3j' bi::h marks: heman-
giomas and mal for ma: ions. Saunclers, Philadelphia
2. Mulliken I, Glowaki I i:9B2; Hemangiomas and vascular
malformations in infams and children: a classification
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2 Predominantly Venous Malformation
Introduction 21
Genetics 21
Clinical Features 21
Fix j I ,ii].i I ' l t r" l i -s e Veil on s Yolloriuaiions 11
Associated Syndromes 22
Blue Rubber Bleb Nevus Syndrome 22
[vtuc'xuuii'.eous i-omikol Ve:'.o'.:f M.dfcim.Lilio
Glomovenous Malformations 22
Maffucci's Syndrome 22
Coagulopathies 22
His top atho logy 22
Imaging 23
Plain Radiograph 23
i '■ 'ppler Ultrasound 23
Computed Tomography 24
Ivi.igntuC Resonance jii.ig.ng 24
A! ;e: iography 24
I 'irect Percutaneous Venography 25
Peripheral Venography 25
Management 26
Medical Treatment 26
Sclerotherapy 26
Technique 27
Sclerosing Agents 28
Laser 29
Surgery 29
Pharmacologic Treatment 29
intensive Care Unit Management 29
Follow-up 31
Outcome .'1
References 31
Introduction
Vascular anomalies are divided into vascular
tumours and vascular malformations. Vascular
malformation classification is based on the anoma-
lous channels: arterial, venous, lymphatic, or cap-
illary. The most frequent vascular anomalies are
venous malformations. The incidence is estimated
to be around 1 in 10,000 [1]. The reader must be
made aware of the numerous confusing n
such as glomangioma, cavernous haemangio
and haeman^ioma that have also been used inp
literature.
Genetics
Venous malformations are sporadic in most cases
but can be inherited. A locus for autosomal-domi-
nant multiple cutaneous and mucosal venous mal-
formations, VMCM1, was identified on chromosome
9p21 [2-4]. A mutation was found in the endothelial
cell-specific receptor tyrosine kinase TIE-2 [5]. This
mutation is likely to occu
ular malforma-
Clinical Features
Professor oi Radiology. Pediatric and Interventional Radi-
ologist, Deportment of Medical Imaging, Hopit.il Ste-itisline,
3175 Cote Ste-Catherine Road, Montreal, Quebec H3T 1C5,
Generally, ven
ous malformations are noted at
birth but can
also appear during infancy. They
involve any tis
sue or organ in all anatomic loca-
tions. Venousn
alformations grow with the patient.
Exacerbations
can occur during puberty or preg-
nancy. Indeed
hormonal modulations of venous
malformations
can be seen during the menstrual
cycle or unde
r anovulant therapy. Surgery or
trauma can als
o lead to the progression of venous
ormal,
.. Hemato-
must include
and d-dimer
malformations. At clinical exam, venous r
formations appear as soft tissue lesions that
compressible, and increase with Vali
vre or gravity. The overlying skin c;
bluish, or purple in colour. The lesii
not pulsatile. Bleeding i
logic evaluation is important an
complete blood count, fibrinogei
dosage. Localized intravascular cons
be observed, especially in extensive venous mal-
formations [6], Coagulopathy can be exacerbated
by sclerotherapy or surgery [7-9]. Extensive facial
venous malformations are frequently associated
with intracranial developmental
lies [10].
Focal and Diffuse Venous Malformations
2.5.3
Glomovenous Malformations
Glomovenous malformations are venous malforma-
tions associated with glomus cells. The smooth layer
is formed by glomus cells, which are smooth muscle
precursor cells [11]. Glomovenous malformations
frequently recur. Sclerotherapy can be useful for
their treatment.
2.5.4
Maffucci's Syndrome
Maffucci's syndrome consists in the association of
venous malformations and multiple enchondro-
mas. Intraosseous venous malformations as well as
enchondromas are responsible for the bony defects
[12].
Venous malformations are either focal or diffuse,
and may involve the skin, the mucosae, the mus-
cles, the bones. In cases of extensive venous mal-
formations, associated distal sites of involvement
Associated Syndromes
2.5.1
Blue Rubber Bleb Nevus Syndrome
Blue rubber bleb nevus syndrome, a rare disorder, is
characterized by continuous development of multi-
ple focal venous malformations of the skin, muscu-
loskeletal tissue, and mucosa throughout the body,
including the gastrointestinal tract. These venous
malformations can be treated by sclerotherapy or
surgery. In some cases of blue rubber bleb nevus,
it has been shown that the mutation may occur on
chromosome 9p.
Coagulopathies
Localized intravascular coagulopathy is reported in
venous malformations. Most patients with venous
malformations have no clinical signs or symp-
toms at presentation. A chronic form of consump-
tive coagulopathy is however possible as shown by
positive d-dimer levels, and normal or low platelets
and fibrinogen values. Consumptive coagulopathy-'
must be corrected prior to initiating the treatment
of vascular malformations. Low- molecular- weight
heparin and elastic stockings are recommended [8].
Administration of cryoprecipitate, platelets, or fresh
frozen plasma to patients with chronic coagulopathy
has proved to be helpful before performing sclero-
therapy or embolization in order toobtai
ful thrombosis [9].
Histopathology
2.5.2
Mucocutaneous Familial Venous Malformations
we due to the abnormal
i wall. Microscopy shows
The characteristics of
venous malformations are the s
blue rubber bled nevus syndroir
of gastrointestinal involvement.
Venous maltormatio
development of the
multiple thin-walled vessels with flattened endothe-
familial lial cells, lacking proliferative I eat u res [1] (quiescent
s those of the endothelium}, and wall smooth muscle deficiency.
pt for the lack The deficient smooth muscle layer leads to the ina-
bility of the affected veins to constrict normally,
!- : red om mainly Veo.ous Malformation
inducing stagnation ol blood, thrombosis, throm- 2.8
bolysis, swelling, and pain [13]. Venous mnlform.i- Imaging
Cions do not exhibit up-regulation of angiogenic
factors or matrix enzymes [14]. 2.8.1
Plain Radiograph
Fig. 2.1. Sixteen-year-old male. Lateral X-ray of the left wris
shows a ventral sect liss-;e mass associated with iypical phle
oclilh in a case of vetoes malformation
Plain radiographs can show phleboliths (Fig. 2.1)
that are suggestive of venous malformation but
rarely present. Soft tissue swelling and bone deform-
ity can be seen.
2.8.2
Doppler Ultrasound
Doppler ultrasound is the initial modality of choice
to differentiate venous malformations from other
vascular abnormalities. Ultrasound is performed
with a high-frequency linear array transducer (5-12
MHz}. On grey-scale images, venous malformations
appear as compress ihlt-ltypoedioic or heterogeneous
lesions [15, 16] (Fig. 2.2a-c). Calcifications (demon-
strated in less than 20% of cases), are quite specific
of venous malformation; anechoic channels can be
seen. Doppler examination displays a monophasic
low-velocity flow (Fig. 2.3). In 20% of venous mal-
formations, no flow can be demonstrated. Dynamic
manoeuvres such as Valsalva or manual compres-
sion are sometimes necessary to induce a visible
Doppler flow.
LfeC:
Fig. >.2a-c. Six-year-old boy with a stable soft tissue mass of
the right temporal region. \> I 1 ? shows a:i heterogeneous hvp-
oechoic well-dekmiled superficial lesion containing anechoic
structures, b The same lesion is compressible and seems nor
vascularized, c Low velocity flow is detected when the com-
pression is released (venous malformation)
4VK9
Fig. 2.3.! : op.\er UJ i:'. a:io:he: pa:ient wilh .1 s;:p eiTiCi.il veno
in aifoi:':.u :o:~. shows lypica! venojs flow on pulse;". Poppler
2.8.3
Computed Tomography
Computed tomography (CT) demonstrates the exten-
sion of venous malformations but the contrast resolu-
tion is less than with MRI. The lesion is hypodense
or heterogeneous with a slow contrast enhancement
after injection of contrast material (Fig. 2.4a,b). Phle-
boliths, when present, are easily seen.
or fast spin-echo Tl-weighted sequences and T2-
weighted sequences with fat suppression (Fig. 2.5a-
d). T2-weighted gradient-echo sequences can be
useful to demonstrate calcification or hemosiderin.
On gradient-echo sequences, the absence of intra-
vascular signal suggests a slow-flow malformation
[17]. Tl-weighted sequences with fat suppression
and gadolinium injection have to be performed to
evaluate the perfusion of the malformation. 3D-FISP
(Fast Imaging with Steady Precision) phlebography
sequence allows the evaluation of draining veins
[18]. On Tl-weighted sequence, venous malforma-
tions are hypo- or isointense. The signal is heteroge-
neous when haemorrhage or thrombosis is present.
On T2 -weighted sequence, the venous malformation
is hyperintense. Areas of hyposignal are related to
thrombosis, phleboliths, or septa, most evident on
gradient images. Small fluid-fluid levels can be
seen. After sclerotherapy, the lesion becomes het-
erogeneous on both Tl- and T2-weighted sequences.
Post gadolinium sequences are useful to evaluate
the residual perfusion. MRI is very helpful for the
delimitation and assessment of the extension, but is
not specific of venous malformations. MRI results
have to be correlated with clinical findings and Dop-
pler examination to reinforce the diagnosis.
2.8.4
Magnetic Resonance Imaging
Magnetic resonance imaging (MRI)
lodality to evaluate the extension of v;
2.8.5
Arteriography
ularmal- Arteriography of the affected limb i
t clinic ally
formations. The MRI protocol includes spin-echo useful, showing either noanomaliesorthe late op.Kiti-
Fig. 2A. a Axial unenhanced c
ervical CT of a
i i-year-old female shov.
s a slightly i'.ypodense mas
s ■.".out;'. in: rig .\ calcified phle-
bolith in the left parotid regio
n.b After contra
st injection, the venous
ma 1 forma tion sligi'.dy enh;'.
aces, remains hypodense and
is be;ter delineated
H'eduniiiianily Wr.oiis M;;!jb:';".\'.ti::i
Fig. 2. 5., i ; :■ 'i ■.■.■.,: I ".". v.-, r ig:i>d MM ,.:.:w- •-..i.:i.v \\y(v: i:v.;j".- : r :'."..: iv \:.::\r i .iz.'. : -..:".i.i." ii^reps. b In short ti
(STIR) sequence, the well-delineated mass is hyper intense, c In T2- weigh ted image, the lesion remain:
d Coronal 11 -weigh .cd scjii after g:i.:cjn:iini injcij; ion .-,ai fat ^1 in nil ion allows skgi-.l m-J h^erogeiieotii enhancement
cation of venous spaces with or without dysplasic
nels.However, ;)[is;ii'j;]M|'liy is sometimes perfori
rule out the presence of an arterial microfistula
2.8.6
Direct Percutaneous Venography
:han- obtained, the opitcil icat ion with a low osmolarity
tedto iodinated contrast is recorded, as a phlebogram.
Three different patterns can be seen: a cavitary
pattern with late filling of normal draining veins
(Fig. 2.6), a spongy appearance with tiny cavities
and late venous drainage (Fig. 2.7), and the dysmor-
phic veins pattern (Fig. 2.8).
Direct percutaneous phlebography is useful in some
atypical venous malformations to allow a precise
diagnosis and mapping of the malformation. Under
ultrasonography, direct puncture of the malforma-
tion is performed with a 20- or 21-gauge needle.
The needle is connected to a syringe through an
extension tubing and is progressively withdrawn
while applying slight suction. Once blood return is
2.8.7
Peripheral Venography
This technique is useful in the presence of complex
venous malformations to evaluate the communica-
tion between the dysmorphic veins and the normal
Fig. 2 A Percutaneous Venography opacifies
l.-le tilling .it :'•:■! ni.i! ;i -.lining wins
■vith Fig.2.7.PeiY'.i;iinecus phlebography o\ a large spongy vi
malformation of the right iliac fossa
Management
A multidisciplinary approach is essential to plan
a treatment strategy specific to each patient. The
modalities of treatment depend on: the localization,
the size, the extension, the functional repercussion,
and the aesthetic impact of the venous malforma-
tion. The goal is to lessen the symptoms and improve
the functional consequences. The management of
venous malformations includes compression, resec-
tion, and obliteration of the channels lumen by scle-
rosing injection or laser photocoagulation.
2.9.1
Medical Treatment
Asymptomatic venous malformations should be
treated conservatively. Counselling regarding the
hazards of puberty, oral contraceptive medication,
and pregnancy has to be provided. Extensive arm
or leg venous malformations should be treated with
elastic stockings. Ant i-int lain ma toiy drugs are help-
ful during the symptomatic thrombosis-related epi-
sodes. Cyclooxygenas [ '-2 (COX-2) inhibitors (such as
Celebrex) have also proved to be effective against
pain. Low- molecular-weight heparin may also be
used to decrease the disseminated intravascular
consumption and is recommended in the preopera-
tive preparation prior to resection. Corticosteroids,
interferon, and other antiangiogenic drugs have
proven useless in the treatment of venous malfor-
[mruoiis.
2.9.2
Sclerotherapy
Sclerotherapy, with or without surgery, is the treat-
ment of choice for symptomatic venous malforma-
tions. Sclerosants destroy the vascular endothelium
through different mechanisms depending on the
agents: chemical agents (iodine or absolute alcohol);
H'edoninianilr Ver.ous Mi'.ooinwtio
osmotic effect (salicylat
detergents (morrhuate sc
canol, and diatrizoate soi
2.9.2.1
Technique
or hypertonic saline);
m, sotradecol, polido-
Ti)[13](Fig.2.9a-d).
Sclerotherapy is performed under fluoroscopic con-
trol. The puncture with a 24 or 22 Cathlon or 20-
gauge Teflon intravenous cannula or other needle
system can be done under ultrasound, CT, or MRI
guidance. It is necessary to ve no graphic ally assess
the draining veins before injecting sclerosing agents
in order to prevent complications. Indeed, an appro-
priate opacification is essential to evaluate the pat-
tern of the lesion, its volume, and the draining veins.
The amount of agent injected is estimated by the ini-
tial amount of contrast medium needed to opacify
the lesion before the visualization of the draining
veins. Additional sclerosant can be needed in order
to obtain a firm lesion on palpation or to dry up
the blood return on aspiration of the cannula. A
tourniquet can be useful. An automated orthopaedic
tourniquet inflated to a pressure below systolic arte-
rial pressure, provides the most effective method of
control [13]. The cuff pressure can be adjusted with
test injections of contrast medium until the drain-
1
in
1
•
(ur-year-old boy with v.
r venous m a Ifor nation.
] important regression
ins malformation of the thigh, a Coron.U an J b axial : iSt MRI show a well delimitated
x months after three sessions of sclerosing ireaiment wi:h alcohol c coronal and d axial
ng veins no longer till. After injection of moder- continuous pulmonary artery pre
ite amounts of absolute ethanol into sequestered during the procedures [23, 26].
'enous malformations of the limb, the tourniquet
s kept inflated for 20-30 min, to minimize the risk Detergent-Type Sclerosants
)f egress of ethanol or clot into the draining veins.
t is wise to release the tourniquet slowly [13]. The The detergent- type of sclerosants .
ourniquet use is controversy. Some groups prefer clerol (polidocanol l%-3%, sodiui
o use amanual compression wirh a gradual decom- fate (STS), sodium morrhuate, and ethanolamine.
iression to avoid pulmonary emboli. Theses detergents can be used in liquid or foam.
in ito ring
icludes: aetoxis-
tetradecyl sul-
Aetoxisclerol (Polidocanol) (3%)
Ethanol (95%-98%)
Absolute ethanol is the most frequently used agent,
and is also the most potent and destructive on the
vascular endothelium. Ethanol causes an instant
precipitation of endothelial cells proteins and rapid
thrombosis. Injection: An undiluted form of etha-
nol, or opacified ethanol with oily contrast medium
(9:1 or 10:2), or opacified ethanol with metrizamide
power under fluoroscopy monitoring [19]. Dose: The
total dose of lml/kg (or 60 cc) per session should
never be exceeded [13]. Ethanol blood levels cor-
relate directly with the amount of ethanol injected.
Complications: Ethanol is the most effective sclero-
sant available but it also results in the most serious
side effects. The most common complication of eth-
anol is local tissue injury, such as skin necrosis (in
10%-15% of cases) [13] or peripheral nerve damage
(in approximately 1% of cases) [13, 17, 20, 21]. Most
complications are transient, but permanent injury
has been reported [20, 22, 23]. Complications rate
for ethanol embolization ranges from 7.5% to 23%.
Severe complications have been reported (cardiac
arrest, pulmonary embolus) [23, 24]. Yakes et al.
[23] reported four cases of cardiopulmonary col-
lapse in out of over 50,000 embolizations or scle-
rotherapy procedures. The mechanism remains
unknown and may include pulmonary vasospasm,
pulmonary embolism and direct card io toxicity.
Central nervous system depression, hypoglycemia,
hypertension, hyperthermia, haemolysis, pulmo-
nary embolism, pulmonary vasospasm, cardiac
arrhythmias, and electromechanical dissociation [9,
13, 17, 21] have been reported in the literature [23, 25,
26]. Continuous cardiovascular monitoring during
the procedure is paramount. When large malforma-
tions are being treated, some have advocated that
such procedures be performed under general anaes-
thesia. Some authors also recommend the use of
This agent is used for the small venous malforma-
tions. Polidocanol is effective by altering the vascu-
lar wall. The emulsion o( netoMsdero! would allow
/eins, thanks to
on could direct
is, sparing then
ii Some authors
for the visualization of the draining
the bubbles; accordingly, this emuls
the compression to the involved veil
the normal adjacent veins. Injectior
used it mixed with a lidocaine soluti
pain after injection. Dose: The quantity is lcc per
cavity [25] up to a total of 6 cc of polidocanol with
0,2-1,0 cc of 1% lidocaine solution. Complications:
Skin necrosis, sciatic neurolysis, and infections were
reported in6-8% of cases [25, 27]. One cardiac arrest
was also reported [28].
Sodium Tetradecyl Sulfate
(Sotradecol-Elkins-Sinn, Cherry Hill, New Jersey)
Sodium tetradecyl sulfate damages the endothelium
resulting in thrombosis and fibrosis. This agent can
be used in a liquid solution or by creating foam with
air. The main difference between liquid solution and
foam is the long life of the foam in the vein and
by the clear separation obtained between the blood
and the sclerosant [29]. Injection: We mix 5 cc of
sotradecol with 2 cc of Lipiodol and 5-10 cc of air.
Tessari described a stable and compact foam qual-
ity using two plastic syringes and a three-way stop-
cock, mixing ratio for sclerosant to air is 1:4 to 1:5
[30-32]. The foam is obtained by mixing the agents
(STS or polidocanol: air) through multiple passages
between two syringes. Dose: The maximum dose is
not well established. Complications: Skin necrosis
was reported by O'donovan [33] in three out of
15 patients.
Ethanolamine Oleate
Ethanolamine oleate is a mixture of 5% eth-
anolamine oleate (Keuk Dong, Inchon, Korea} and
iodized oil (Lipiodol) (ratio 5:1-5:2); the amount
i-T^d'.'iiii^.iiiilv Veii'.'iii W; , .j"'"::'\':ti::'
used ranges from 2 to 20 ml within 1 to 10 sessions.
This salt of an unsaturated fatty acid has been
used as a sclerosing agent because it has excellent
thrombosing properties [34]. Approximately 50%
of oleic acid combines with serum proteins within
30 minutes [21]. This can cause renal toxicity in
association with a marked intravascular haemo-
lysis and hemoglobinuria and hepatotoxicity [34].
To prevent these complications, haptoglobin can
be administrated intravenously during and after
the injection of the sclerosant into the lesion [35].
Effective in 92% (23 out of 25) of cases, Konez et
al. [36] reported the conjoint use of coils emboliza-
tion as well as inflated balloons within the internal
jugular vein in cases of cervicofacial venous mal-
formations in order to prevent the systemic passage
of the sclerosant. Trismus in two patients, abated
completely within 1 week.
Ethibloc (Ethicon, Hamburg)
Ethibloc is not available in the United States. Ethi-
bloc is a mixture of zein (corn protein), alcohol,
and contrast medium. The sclerosing effect is due to
the giant cell inflammatory reaction. Injection: The
product is available in a preloaded syringe. Compli-
cations: No significant lasting complication, except
for the extrusion of the agent in 10% of cases [25].
Dubois et al. [37] reported 74% of good or excellent
results in 28 out of 38 patients.
Histoacryl
Histoacryl is a biological product that undergoes
polymerization on contact with an ionic substance,
inducing then a permanent occlusion. Mostly used
as a pre-surgical step, it was reported for the treat-
ment of venous malformations of the orbit [38].
Delay in healing up may be due to the extrusion of
the Histoacryl when left in place.
In the presence of rapid venous drainage
venous spaces, placement of coils can be useful to
retain sclerosing agent and avoid pulmonary embo-
lus, particularly in a venous malformations close
to normal veins. Coils can be delivered directly
through the access needle into the venous spaces
or via the femoral or jugular vein (Fig. 2.10a-e). For
limb superficial venous malformations, a periph-
eral intravenous catheter can be useful to perform
a phlebography during sclerotherapy for assess-
ing the ischemic changes. Applying cold sterile
saline onto the surface of the skin to induce local
vasoconstriction seems to reduce the risk of skin
damage [13].
2.9.3
Laser
Effective intralesional laser therapy was reported
by Derby and Low [39] in cases of facial venous
malformations. Pulse dye laser operation has been
found to be most successful in removing hundred of
lesions in cases of blue rubber bleb nevus syndrome,
without recurrence [40].
2.9.4
Surgery
In the majority of cases, successful sclerosing treat-
ment will obviate the need for surgery [41]. Surgery
alone is only effective in well-defined and easily
accessible lesions of moderate size in which the
anatomy will allow for a maximal functional resto-
ration. Serious complications such as bleeding and
nerve injury can occur with surgery.
2.9.5
Pharmacologic Treatment
Corticosteroids, interferon, other antiangiogenic
drugs are useless in cases of venous malforma-
Intensive Care Unit Management
Airway obstruction in the case of neck lesions,
and compartment syndrome in extremities lesions
should be carefully observed and managed accord-
ingly (tracheostomy, fasciotomy). Systemic corti-
costeroid (dexamethasone 0.1 mg/kg intravenously
every 8 h), and ice packs can be helpful to n
the swelling. Gross hemoglobinuria c
ally occur and is managed by hydratationand urine
alkalization (95% dextrose and water mixed with
75 mEq/L of sodium bicarbonate], administered at
twice the maintenance rate. Urine is monitored visu-
ally and usually clears within 6 h.
Table 2.1. Matenols for sclerotherapy
• Puncture needles
• Butterfly needle: 25G or
• Jelco 20G, 22G, 24G
• Sclerosing agents
HOW tO US? iOLMClflCJ
m)
Ethanol 7 cc ethanol '.villi irw.i'izaniide powdei i 3.75 g) or Max: 1 cc/kg
With nonionic contrast medium
_ l % Sodiu:v. Tel:.idecy. Wiih ivietriz.imide powder or Max:30 cc/session
Sulfate (Sotradecol] Diluted contrast medium
Foam = Mix: Maximum:
(Fig. 2.111 • 5 cc Sotradecol not well established
• 2 cc Lipiodol Our recommendation lii cc/sessio.
i-redomiiianily Venous iv!;:!jb: :":• .;tj;:-
2,11
Follow-up
Incase of skin necrosis, weekly surveillance is recom-
mended, to exclude superimposed infection. When
necessary, the referral to a specialized wound centre
is mandatory for possible debridement and/or skin
grafting. In the absence of complications, a 6-week
post-procedure follow-up is indicated to evaluate the
need for other si
2.12
Outcome
The reported outcome of endovascular treatment of
venous malformation has been extremely variable
from one series to another. No series has been reported
based upon strict MRI documentation and sufficient
follow-up. No predictors of success have been clearly
outlined. Overall, it appears that favourable results
may depend on the extension of the venous malfor-
mations and the number of sclerotherapy sessions.
Recurrence due to recanalization of treated venous
malformations is more likely in cases of diffuse
involvement with associated coagulopathy [13].
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Trauma and Iatrogenic Lesions
Recognition and Treatment of Medical Emergencies
in the Trauma Patient
Lucy Wibben
* and Melhem J. Sha
Inlioduction 35
Airway Compromise 35
Recognition 35
Treatment Adjuncts 36
Definitive Control 37
Circulatory Shock 38
Recognition 38
Resuscitation 39
Pitfalls of Resuscitation 40
Cookbook: Recognition and Tiealmenl of Medical
Emergencies in the Trauma Patient 40
References 41
ist may occasionally be the only physician avail-
able to provide timely recognition and prompt, sys-
tematic treatment of life-threatening emergencies.
Adequate treatment of these emergencies is essential
for optimizing the care of the trauma patient. This
chapter will discuss recognition and treatment of
two common life-threatening emergencies that the
interventional radiologist may be the first physi-
cian to encounter in the trauma patient. Definitive
treatment will be presented for completeness and
further study.
Introduction
The role of interventional radiology (IR) is expand-
ing in the care of the acutely injured polytrauma
patient. The interventional radiologist is often asked
to perform therapeutic embolization of active bleed-
ins from mlTnnhrlominal solid organ injuries and
pelvic arterial injuries to provide initial control
[1-3]. These patients are often accompanied by a
traumatologist while in the interventional suite.
They are often ventilated and actively receiving
blood products. When these patients are critically
ill and potentially unstable, the interventionist can
delegate their critical care to the traumatologist.
However, the challenge to the interventionist occurs
in the setting of the "presumed stable" trauma
patient with compensated shock. The intervention-
Airway Compromise
3.2.1
Recognition
The airway of an acutely unstable patient should be
addressed first. The American College of Surgeons
addresses the airway as the initial step of the primary
survey in the Advance Trauma Life Support Protocol
for evaluation of trauma patients (Table 3.1) [4]. The
primary survey addresses all life-threatening inju-
ries in an expedient manner by systematic review of
all the systems. The primary survey protocol also
works well to address any acutely decompensating
patient. Airway emergencies in a previously stable
patient can occur as a result of on-going cervical
edema or hematoma from soft tissue injury or frac-
tures. It can also accompany mental status deterio-
*,MD
L.A.WlBBENV
University of
Radiology, 200 Hawkins D:
M. Shahafuddin.MD
University :n Iowa Hospi litis and Clinics. Pepa? intent of Rad
ology,200 Hawkins Dr., 3957 ]PP, Iowa City, IA 52242, USA
and Clinics, Department of
ira City, IA 52242, USA
Table 3.1. The primary survey of the trauma patient. Fro
[37], with permission
A Airway maintenance with ceivical spine protection
B Breathing and ventilation
C Circulation with hemorrhage control
D Disability: Neurologic status
E Exposure/environmental control:
Completely undress the patient, but prevent hypothermi
L. VVibbeaniryer and M. Sh.i rafted in
ration, circulatory decompensation, or administra-
tion of procedural conscious sedation medications.
It is therefore imperative that the interventionist be
familiar with the signs and symptoms of impending
respiratory collapse and the treatment.
Airway compromise may be insidious in onset.
Recognition of the signs and symptoms of airway
obstruction can enable controlled airway access
and prevent a respiratory arrest. Table 3.2 lists the
signs of impending respiratory embarrassment sec-
ondary to airway obstruction. Stridor or inspiratory
wheezing heard over the cervical region is a sensi-
tive marker for impending respiratory compromise.
Signs of increased labored breathing should also
be observed. Flaring of the nasal alae, retraction of
cervical soft tissues, and retraction of the ribs on
inspiration all are signs of increased work of breath-
ing. Paradoxical movement of the chest (abdominal
distention on inspiration) is an ominous sign sug-
gesting impending airway compromise.
Adequate oxygenation and ventilation should be
assessed. The pulse oximeter data is readily avail-
able to the interventionist during the procedure
and can provide quantitative data reflecting the
patient's ability to oxygenate. Saturations above
95% are usually adequate to ensure sufficient oxy-
genation [4]. However, due to the sigmoidal shape
of the oxyhemoglobin desaturation curve, factors
that shift the curve to the left such as hypothermia,
alkalosis, and a decrease in 2,3-diphosphoglycer-
aldehyde (old banked blood) may ii
oxyger
unloading from oxyht
patients should r>
oxygen by nasal cannula or m
ation, adequate ventilation cai
accessed by arterial blood gas ;
ing normal carbia. Inadequate
ation or ventilation accompanit
of labored breathing should prompt c
i ■ :> r intubation.
efficient
iglobin. Therefore,
^ceive supplemental
ask. Unlike oxygen-
i only be accurately
iiia lysis demonstrat-
or marginal oxygen-
id by increased signs
3.2.2
Treatment Adjuncts
Several options are available lor the initial man-
agement of suspected airway obstruction. If neuro-
logic deterioration secondary to closed head injury
or administration of sedative agents is suspected, a
soft plastic nasopharyngeal airway (trumpet) can be
inserted (Fig. 3.1} [5-7]. Its counterpart the oropha-
ryngeal should be avoided in the conscious patient
because of excessive irritation of the upper airway.
The nasopharyngeal airway will lift the tongue and
accompanying soft tissues off the back of the airway,
enabling ventilation. In addition, a gentle chin lift
or jaw thrust can alleviate upper airway obstruction
(Fig. 3.2). These maneuvers alone may be sufficient
if only upper airway obstruction is the problem. It
should be remembered that extension of the neck
: 3.2. Symptoms and sign- of [es^i:\r.o:y obsinKkon g:adra according to sever-
lodified from [38,39], with permission. First published in the British Medical
Stage
Signs and Symptoms
1. Mild or Potential Obstruc
on Hoarseness
Cough
No stridor at rest
Stridor on moderate exertion
2. Moderate Obstruction
I'iyv. ■■:•■?;:
Rib retraction on inspiration
Use of accessory muscles of aspiration
Stridor on slight exertion
3. Severe Obstruction
Apprehension
Ke<: Issues?
Sweating and pallor
Increased blood pressure and heart rate
Paradoxical movement of chest
Stridor at rest
4. Total Obstruction
Slowed respirations
Marked cyanosis
Impaired consciousness
Slowing heart rate
Hypotension
No longer stridorous
Recognition and :re.iunem of Hec.;.i. Emergencies in the Trauma Patient
Fig. 3.1. The mechanis:r. •:■: orophai 'y:;ge:il obstriicr io:i in the Fig. 3.2. Manual in -line stabiliziitio:
supine position and die projet pi a cement of die nasop:'.a:yn- ah way is opened with the two-han
geal airway. Modified from [42], with perm is si on. G:-pvi ight, ing technique
n Heart Association
s pi' 'vided as :iie oadeir.'s
d jaw thrusi airway ope:i-
should be avoided in all t
til thei
a patients
cervical spine is radiographically and clinically
cleared. These patients will almost invariably have
hard cervical collars tor ned-. immobilization, and
these should never be removed withi
sulfation with the trauma ten in.
3.2.3
Definitive Control
it propel
If the patient continues to show sigi
obstruction or compromise, despite tht
a nasopharyngeal airway or manual airway opening
procedure, a definitive airway needs to be estab-
lished. Trauma patients have challenging airways
due to the need to maintain manual in-line neck
stabilization (MILS) and the presence of the cervical
collar. Normally patients are placed in the sniff-
ing position with the head and upper neck fully
extended and the occiput slightly elevated. This
position aligns the oral, pharyngeal, and laryngeal
airways. MILS places the head in the neutral posi-
tion, displacing the larynx anteriorly and impairing
visualization [8,9]. The anterior faceplate of the cer-
vical collar restricts mouth opening, further com-
plicating access to the larynx [9]. Removal of the
anterior faceplate as long as .MILS is maintained is
safe and will facilitate intubation. When available,
an experienced provider should attempt definitive
control of a the airway. However, as the intervention-
ist may occasionally be the only one immediately
available, a systematic approach to the definitive
airway will be presented.
A systematic approach to the airway consists of
assessment of the level of airway difficulty, prepara-
tion of the patient, collection of airway equipment
and pharmacologic, medication, and development
of a back-up plan. A back-up plan is essential prior
to any intubation attempt. Preparation is critical to
avoid failed attempts resulting in airway trauma
impairing subsequent laryngoscopies.
The first step, assessment of the level of airway
difficulty, is critical. An unanticipated difficult
airway can lead to a no intubation-no ventilation
crisis where only a surgical airway can correct the
situation. It is estimated that anywhere from 1.5%-
8.5% of airways are diilicult [10]. I 'espite a number
of scoring systems that rate airway difficulty, only
50% of these difficult airways can be accurately pre-
dicted [11-13]. In general, patients who are difficult
to intubate often have limited mouth opening, pro-
truding teeth, receding chins, short necks, or lim-
ited neck extension. The existing difficult airway
scoring systems take into account these factors. If a
difficult airway is anticipated, other options such as
an awake intubation, Laryngeal Mask Airway, gum
bougie, or a lighted stylet can be considered [7,14].
Patients need to be preoxygenated prior to intu-
bation. Preoxygenation washes out the nitrogen and
ensures adequate oxygenation if prolonged laryn-
goscopy is needed. In the spontaneously breathing
trauma patient, this is done by giving them high
flow oxygen via a non-rebreathing mask or a bag
L. VVibbenniryer nnJ M. '•iiaiiif.uldin
valve mask device. In the case of the no n- ventilating
patient, their ventilation must be provided through
manual compression of a bag valve mask device.
This is best done using a two-person technique. The
mask is placed over the bridge of the nose with the
thumbs and then secured over the mouth and chin
area with the index and middle fingers. The ring and
little fingers support the jaw in the jaw thrust posi-
tion. An additional person is needed to compress the
ventilating bag.
Necessary equipment and pharmacologic medi-
cation then needs to be made available to ensure
smooth intubation. Essential equipment is listed
in Table 3.3. Pharmacologic medications consist
of hypnotic and paralytic agents and are listed in
Table 3.4. All patients should have cardiopulmo-
nary monitoring with cardiac, blood pressure, and
pulse oximeter monitors. Intravenous lines should
be checked for their patency. The choice of seda-
tive or hypnotic agents will depend on the patient's
hemodynamic status, with etomidate and ketamine
usually preferred in the hemodynamically unstable
patient. The administration of a paralytic agent has
Table 3.3. Essen:!;!! ;n: \\~\y mjn; ! .geine;':". equipment. Modifirci
from [40], p. 6, with permission
• Supply of 100 c '" oxygen
• Bag valve device
• Suction equipment
- Suction catheters
- Large-bore tonsil auction apparatus (Y;mknuer)
• Stylet
• Oral airways
• Nasal airways
• Laryngoscope handle ,ind baices
(curved, straight, various sizes)
• Endotracheal iubes (various sizes i
• Tongue depressors
• Syringe tor cuff inflation
• Tape
• Tincture of benzoin
Table 3 A Pharmacologic therapy tor intubation. Modified
from [41], with pt
< 60 si
been demonstrated to help with successful intuba-
tion [15,16]. However, the choice of a paralytic will
depend on the difficulty of the airway and the abil-
ity of the airway provider. A depolarizing paralytic
(succinylcholine) is ideal as it results in rapid induc-
tion and has the shortest half-life of all the paralyt-
ics. However, its use should be restricted in patients
with known neuromuscular disease, massive mus-
cular trauma, burn injuries over 24 hours old, or
suspected elevation in serum potassium. Non-depo-
larizing paralytics should be reserved for patients
with easy airways and experienced airway provid-
ers, since paralysis can last up to 120 minutes.
Conscious trauma patients are intubated by the
technique of rapid sequence intubation (RSI) with
MILS. Unconscious patients can be intubated with-
out medication. RSI calls for administration of a sed-
ative or hypnotic agent followed by a paralytic agent.
Another team member provides MILS by cradling
the trauma victim's neck between their arms, effec-
tively preventing neck extension (Fig 3.2). Exter-
nal cricoid pressure (8 kg of pressure applied with
three fingers over the cricoid ring) is applied prior
to the administration of medication to decrease the
risk of aspiration. The patient is then intubated,
and verification of correct positioning of the tube
is performed by physical exam and disposable cap-
nography to assess for exhaled carbon dioxide. Fur-
ther discussion of intubation techniques is beyond
the scope of this chapter; the interested reader is
referred to several references [14,17-19].
0.1-0.3 mg/kg 30-60 sec 6-15 rain
1-1.5 mg/kg 30-60 sec 5-10 rain
0.4 mg/kg 60-90 sec 75-1 00 rr
0.3 mg/kg 60-90 sec > 120 mil
0.9-1.2 rag/kg 60 sec > 60 rain
Circulatory Shock
3.3.1
Recognition
Once an adequate airway and breathing of the
trauma patient is achieved, the primary survey of
the trauma patient addresses the circulatory system.
A number of perfusion endpoints must be analyzed
to determine whether the patient is adequately
resuscitated or declining into circulatory shock. The
predominate cause of shock in the trauma patient is
under-perfusion secondary to bleeding. The treat-
ment of shock is to replace the volume lost. By and
large, the treatment of shock in the trauma patient
has remained unchanged for the past few decades.
The recognition of shock, however, can be chal-
lenging. Blood pressure and pulse are neither sensi-
Recognition an;; . re.iunem of Hec.;.i. Emergen ci-
five nor specific markers for the diagnosis of early
hemodynamic shock [20-22]. In fact, hypotension
can Lie a late finding in shock after which circula-
tory collapse can occur. In general, the signs and
symptoms of shock are directly related to the blood
volume lost [4]. The American College of Surgeons
divides hemorrhage into four categories (Table 3.5).
Most patients tolerate class-1 hemorrhage or 10%
blood volume loss with little change in vital signs,
due to a number of compensatory mechanisms,
the earliest of which are tachycardia and narrowed
pulse pressure (the difference between the sys-
tolic and the diastolic pressures). It loss continues,
the patient will demonstrate a decrease in cardiac
output and blood pressure. As a result pallor, cool
extremities, delayed capillary perfusion, decreased
urine output, and mental status changes (agitation
and anxiety) may develop. Although these signs may
occur before, they are usually minutes ted in i.idulls
following around 20'-'('--40 IJ r> blood volume loss and
therefore are late markers of shock. Children, on
the other hand, may not manifest these signs until
around 40% volume loss. Children with hypotension
and tachycardia are significantly volume-depleted
and can rapidly decompensate.
Biochemical markers may better quantify the
initial and on-going magnitude of the shock state
[22-26]). Both the base deficit and serum lactic
acid level measure the acidosis produced by the
anaerobic state during inadequate delivery of sub-
strate to tissues [2~]. Shock impairs nutritive blood
flow to tissues, shifting cellular metabolism into
the less efficient anaerobic glycolysis pathway. The
formation of ATP from ADP is slowed, resulting in
accumulation of hydrogen ion (H + ) in the cytosol
and extracellular fluid. This accumulation of the
H + in the cytosol is quantified by the base deficit
n the arterial blood gas. Base deficit
(the quantity of strong acid or base that would be
required to titrate the patient to a normal pH assum-
ing aPaCO 2 of40 mmHgand a hemoglobin of 5 g/dl)
reflects the metabolic component of shock. Initial
and subsequent base deficit measurements provide
markers to access the severity and recovery of the
shock state. Initial base deficit < -6 has been asso-
ciated with the need for transfusion [25]. Similar
to the base deficit, lactic acid accumulates in the
shock state. Under anaerobic conditions, pyruvate
accumulates and is dehydrogenated in the cytosol
to lactate. Lactate buffers H 4 ", resulting in lactic acid.
Serial measurement of serum lactate can also help
achieve a better follow-up of the compensated shock
state and reduce the need for on-going resuscitation.
Persistent serum lactate elevation following resus-
citation in trauma has been reported to portend a
worse outcome [23].
3.3.2
Resuscitation
Once shock is identified, resuscitation needs to be
instituted to prevent on-going perfusion mismatch,
which can lead to multiple system organ failure and
death. Although there is some controversy regard-
ing resuscitating penetrating trauma victims to
normal blood pressure before surgical control of
their bleeding, resuscitation to normal volemia is
the current pnradigm in bluntly injured patients
[28]. In penetrating trauma victims, normotension
may lead to worsened hemorrhage, whereas blunt
trauma patients often have accompanying head inju-
ries that can be significantly worsened by hypoten-
sion. Trauma patients in shock are first resuscitated
with crystalloid, namely Lactated Ringers or normal
saline. ATLS protocol dictates a 2-liter rapid bolus
Table 3.5. Estimated fUiic ami iMood losses based on
hemorrhagic shock se
verity class on patient's
inidal presentation. From
[42], with permis
Class I
Class II
Class III
Class IV
Blood loss (ml)
Up to 750
750-1500
1500-2000
>2000
Blood loss (% blood vi
>lnme)
Up to 15%
15%-30%
30%-40%
>40%
Pulse rate
< 100
MOO
> 120
>140
Blood pressure
Normal
K : :■ [" m ..i 1
i ■e.:r-;i ,; ;d
', -ecie.ised
Pulse pressure
Normal or increases
Decreased
i 'ecreased
recreated
(mmHg)
Respiratory rate
14-20
20-30
30-40
>35
Urine output
>30
20-30
5-15
Ned. id: .-
(ml/h)
CNS/mental statu
Slightly anxious
Mildly anxious
Anxious, confused
Confused, lethargic
Fluid replacemen
t(3:l
rule)
ill vsiaKoid
'..'iVsLlllOld
Crystalloid and blood Crystalloid and blood
L. VVibbeaniryer nnJ M. 5l"i.n I ]f'.:cidin
in an adult and a 20cc/kg bolus in a child. Non-
responders or transient hemodynamic responders
usually have lost > 25% of their blood volume or
have on-going bleeding and need to receive blood.
As typing and cross-matching require time, type O
negative blood is preferentially transfused. It is cru-
cial to remember that the ability to provide adequate
resuscitation is also dependent on catheter dynam-
ics. ATLS protocol dictates the placement of two
large-bore (14-16 gauge) peripheral catheters. With
short intravenous tubing (< 3 feet) and 300 mmHg
external compression, these catheters can provide
flow rates of 249-500 cc/min [29]. Central access is
required if peripheral access is inadequate. The loca-
tion of the placement of catheters is also important.
The lower extremities should be avoided if intraab-
dominal injury is suspected.
3.3.3
Pitfalls of Resuscitation
Tlie two main pi I hills ot rapid resuscitation and mas-
sive transfusion are hypothermia and coagulopathy.
Along with acidosis of the shock state, hypothermia
and coagulopathy compose the "triangle of death"
well known to the trauma surgeon [30,31]. When
these three conditions are present in the emergency
room or operating room, only stabilizing procedures
are performed and the patient is transferred to the
intensive care unit for resuscitation. With resolution
of the triad, the patient is returned to the operating
room if necessary.
Hypothermia in the trauma patient is nui hi facto-
rial, resulting from exposure to cold environment,
bleeding, and infusion of cold fluids. Mild to mod-
erate hypothermia (34°C to 30°C) can be associated
with coagulopathy that can impair the patient's
response to ongoing resuscitation and at times be
refractory to treatment [32]. During massive resus-
citation, hypothermia can be avoided by admin-
istration of warmed fluids, either by means of an
in-line warmer, or rapid infuser. The ambient room
temperature should be maintained at 21°C. Addi-
tionally, patients can also be actively warmed by one
of the commercially available convective blankets.
Coagulopathy can also be multifactorial in the
multiple injured trauma patients. In addition to
hypothermia-related coagulopathy, massive resusci-
tation and massive transfusion are other important
causes. Massive resuscitation can lead to throm-
bocytopenia, prolonged prothrombin times, and
decreased fibrinogen [32,33]. The incidence of coag-
ulopathy during resuscitation is variable, and there-
fore its treatment remains controversial. Although
some formulas have been proposed for replacement
of coagulation factors and platelets based on the
number of units of blood received, several studies
have failed to show their reliability [34,35]. Without
obvious microvascular bleeding, many recommend
that fresh frozen plasma and platelet replacement be
guided by laboratory abnormalities [33,36].
Cookbook:
Recognition and Treatment of Medical
Emergencies in the Trauma Patient
Susgect Airway Compromise
• Perform Primary Survey
• Assess Airway for Patency
• Open Airway
- Airway Opening Procedure
- Insertion of Naso- or Oropharyngeal Airway
• Prepare for Definitive Airway
- Assessment of Airway Difficulty
- Preoxygenation
- Collection of Equipment
- Development of a Back-up Plan
• Provide Definitive Airway-Intubation
• Confirm Placement of Airway
- Auscultation
- Capnography
- Chest Radiograph
Suspect Ciratl.iton Compromise
• Perform Primary Survey
• Assess Circulation
- Look for signs of perfusion abnormalities
- Hypotension, tachycardia, diaphoresis,
agitation, pallor
- Obtain biochemical markers of perfusion
abnormalities (base deficit and lactic acid}
• Provide Resuscitation
- Crystalloid (Ringer lactate) bolus
- Packed red blood cells for no n- res ponders
• Avoid hypothermia
- Warm room to 20°C
- Warm fluids
- Warm patient with a convective blanket
• Assess for secondary coagulopathy during
massive resuscitation
- Obtain blood for PT, INR, PTT, Fibrinogen
Recognition and . reatmenl of Mefhi.il Emergence:
niicipated dif-
.lagement (see
Pondeknger RF, Trotteur G et al. (2002) Traumatic inju-
ries: radiological hemostatic intervention ai admission. Eur
Radiol 12:979-993
Velmahos GC, Toutouzas KG et aL (2002) A prospective
study i'n I he safety and efficacy of angiographic emboli za-
tion i"o: pelvic ai;d visceral Minnies. I Trauma Injury Infect
Grit Care 53:303-303
Santucci RA.Wessells H et al. (2004) Evaluation and man-
a gem en; of renal injuries: consensus statement of I he renal
trauma subcommittee. BJU Int 93:937-954
American College o:' Surgeons i I 997; Advanced iraun'.a life
support manual, nth edn. ACS, Chicago
Kaur 5, Hearc SO (1996) Airway management and endo-
tracheal intubation. In: Rippe IM, Irwin RS, Fink MP, Cera
FB teds: Intensive care medicine, vol I . Little Brown. New
York, pp 1-15
Hillman DR, Piatt PR et al. (2003) The upper airway during
anaesthesia. Br I Anaesth 91:31-39
Nolan JP, Wilson ME (1993) Orotracheal intubation in
patient- with potential cervical spine injuries. An indica-
tion for the gam eiasi.c bougie ; -re comment !. Armies the si a
48:630-633
Heath KJ (1994) The effect of laryngoscopy of different
cervical spine immobilisation techniques
Anaesthesia 49:843-845
Crosby ET, Cooper RM et al. (1998) The u
ficall airway wait re com men canons ho: i
comment). Can J Anaesth 45:757-776
Oates JD, Macleod AD et al. (1991) Comparison of two
nre ih:: as for predicting cl it'll cult ; in u bar ion :. ser comment).
Br ] Anaesth 66:305-309
ll.Sawa D (1994) Prediction of difficult tracheal intubation
(see comment). Br J Anaesth 73:149-153
Rosenblatt WH :2l.:.4: Preoperative planning of airway
managiriiient in critical care patients (see comment). Crit
Care Med 32 [Suppl 4]
Blanda \1, Callo 'JE :2C0ai Emergencv airwav manage-
ment Emerg Med Clin North Am 21:1-26
C 1 1 swell IC, Parr M J et al. (1994) Emergencv airway man-
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Li J, Murphy-Lavoie H et al. (1999) Complications of emer-
gency imubaiion wilh and wilhout paralysis. Am 1 Emerg
Med 17:141-143
Behringer EC i2032! Approaches [.:■ managing the upper
airway. Anesthesiol Clin North Am 20:813-832
Orebaagh SL f 200 J ) Pirllcuk airwav management in the
emergency department. ) Emerg Med 22:31-48
Butler KH, Clyne B (2003) Management of the difficult
airway: alternative airwav leohniques and admncts, Emerg
Med Clin North Am 21:259-289
luna GK, Eddy AC et al. (1989) The sensitivity of vital signs
in io enti lying major thoracoabdominal hemorrhage. Am 1
Surg 157:512-515
Thompson D.Adams SL et al. (1990) Relative bradycardia in
patients Wilh isclaieol penetrating aodommal irauma and
isolated extremity trauma. Ann Emerg Med 19:263-275
Wilson M, Davis PP ei a I. (2303 i Diagnosis and monitoring
of hemorrhagic shock oaring the initial resuscitation of
multiple trauma patients: a review. J Emerg Med 24:413-
422
22. Abramson D, Scalea TM et al. (1993) Lactate clearance and
survival following injury. 1 Trauma iniury Infect Crit Care
35:584-588
23. Manikis P, lankowski S el al. ( 1995) Correlation of serial
blood lactate levels no organ failure and mortality after
trauma. Am ] Emerg Med 13:619-22
24. Davis JW, Parks SN et al. (1996) Admission base deficit pre-
dicts transfusion requirement and risk or" complications
(see comment). J Trauma Injury Infect Crit Care 41:769-
25.Davis )W, Kaups KL et al. (1998) Base deficit i
io pH in evaluating clearance of acidosis after
shock. J Trauma Injury Infection & Crit Cai
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penetrating icrso iniuries (see comment). N Engl 1 Meil
331:1105-1109
28.Millikan JS, Cain TL et al. (1984) Rapid volume replace-
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197:532-535
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34:481-485
33.Harrigan C, Lucas CE et al. (1985) Serial changes in
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34.Wudel JH, Morris JA Jr et al. (1991) Massive transfusion:
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Crit Care 31:1-7
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between hypothermic coagulopathy and clotting -ladies.
J Trauma Injury Infect Crit Care 33:465-470
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DV, Moore EE (eds) Trauma, 4th edn. McGraw-Hill, New
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37.Mattox KL, Feliciano DV, Moore EE (eds) (2000) Trauma,
4th edn. McGraw-Hill, New York
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Br Med J 1:369
39.Rippe JM, Irwin RS, Fink MP, Cerra FB (1996) Intensive
care medicine, 3rd edn. Little Brown, Boston
40.Hartmannsbruber (2000) The traumatic airway: the anes-
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Clin 38:87-104
41. Cummins RO (ed) (1994) Textbook of advance cardiac life
support. American Heart Assoc ia iron, Dallas, Texas
4 Visceral and Abdominal Solid Organ Trauma
Gary Siskin and Jafar Golza
Splenic Artery Embolization 43
Introduction 43
Patient Selection 43
The Role of Abdominal CT 44
. Diagnostic Angiography 44
Splenic Artery Embolization 45
Technique 45
; Results 47
■ Post-Embolization Follow-up 48
Hepatic Artery Embolization 48
Patient Selection 4S
lagnos:
49
Hepatic Artery Embolization 49
Technique 49
Results 49
Post-Embolization Follow-up 51
Renal Artery Embolization 51
Patient Selection 5J
[ 'iagnosis of Renin Vascular Injury 52
Renal A: tery Embolization 52
Technique 52
Results 52
Post-Embolizatio
Cookbook 54
References 55
Follow-up
Splenic Artery Embolization
4.1.1
Introduction
During the past 10-15 years, there has been a clear
trend among trauma surgeons toward the use of bed
rest and observation for hemodynamically stable
G. Siskin, MD
Albany Medical College, Vascular Radiology,.
Scotland Avenue, Albany, NY 12208-3479, USA
J. GOLZARIAN, MD
Professor of Radiology. I a:ector. Vascular anc Interventional
Radiology, University of Iowa, Department of Radiology.
200 Hawkins Drive, 3957 fPP, Iowa City, IA 52242, USA
patients after blunt injury to the spleen [1], How-
ever, well-defined criteria are still not available to
apply to these patients in order to determine who is
best suited for nonoperative management and who
will ultimately require surgery. We do know that
liemodviiaiiiically unstable patients with multisys-
tem trauma and significant intraperitoneal bleeding
will likely not be successfully managed with obser-
vation and splenic salvage. All other hemodynami-
cally stable patients are now considered candidates
for nonoperative treatment consisting of observa-
tion with serial physical examination, frequent
hematocrit determinations, bed rest, and limited
oral intake [2].
The trend toward nonoperative management
after splenic injury has significant benefits for this
patient population. These include eliminating the
risks for immediate and late complications asso-
ciated with open surgery as well as preserving the
immunologic functions provided by the spleen [1,
3-5]. Immunologically, the spleen is best known for
its filtering function, which serves to remove partic-
ulate antigens, bacteria, and old erythrocytes from
circulation [6]. In addition to this, the spleen pro-
duces mediators such as immunoglobulin M, tuft-
sin, and properdin [6, 7]. The importance of these
functions manifests itself after splenectomy with
a significant post-surgical infection rate, which is
what initially prompted surgeons to increase their
interest in splenic salvage [6-9].
4.1.2
Patient Selection
With the benel its ot splenic salvage rarely questioned,
it makes sense that this is most desirable option for
most, it not all, lieinodynamically stable patients.
However, it is still not known with certainty which
patients will be success! tillv managed with nonopera-
tive management and which will ultimately require
surgery despite initially being considered candi-
dates for observation. Patient age, injury severity
C-. Siskin ;i:id 1. L,olz;i:i,in
score, neurologic status, grade of injury on abdomi-
nal CT, and quantity of hemoperitoneum have all
been cited as factors that may affect the success of
nonoperative management [10-15]. Hemodynamic
stability as a reflection of injury severity is likely
the most important factor to consider; Peitzman et
al. found that nonoperative management was more
likely to be successful in patients with higher blood
pressure, higher hematocrit levels, less severe injury,
and smaller quantity of hemoperitoneum [15]. Early
on, it was recommended that patients older than age
55 be excluded from nonoperative management of
blunt splenic injuries [10, 16]. However, more recent
data suggest that the decision to pursue nonoperative
management should be based on clinical and hemo-
dynamic factors, and not necessarily on age [11, 17].
Despite the benefits of splenic salvage and the
trend towards nonoperative management for these
patients, there are those that advocate a more aggres-
sive approach to the treatment of splenic injuries.
These investigators cite the potential for delayed
rupture or progression of injury that may require
urgent transfusion or emergency splenectomy.
Federle et al. did note in the review of their insti-
tutional experience with splenic trauma patients
that 15% of patients selected for nonoperative man-
agement initially ultimately required surgery, most
commonly within 48 hours of presentation [18]. One
problem with managing patients with delayed rup-
ture or injury progression is the difficulty utilizing
techniques to preserve splenic tissue, such as par-
tial splenectomy and splenorrhaphy, depending on
clinical severity [19-22].
4.1.3
Diagnosis
4.1.3.1
The Role of Abdominal CT
Abdominal CT has become an integral part of the
evaluation of patients experiencing blunt traumatic
injury. For stable patients with splenic trauma,
CT is needed before a decision is made to proceed
with nonoperative therapy because it is important
to identify and characterize not only the degree of
splenic injury, but also any concomitant abdominal
injury [19, 23, 24]. There have been several CT-based
classification systems tor splenic injury, based on the
morphologic grade of splenic injury and the amount
of intraperitoneal hemorrhage, to guide therapy and
predict success for nonoperative management [18,
25-29]. One example of a grading system for splenic
injury is the modified criteria of the American Asso-
ciation for the Surgery of Trauma (AAST), which
grades splenic injuries from 1 to 5 on the basis of
increasing severity of parenchymal damage based
on radiologic assessment [18, 27] (Table 4.1). Despite
the widespread use of this and other classification
systems, their use remains controversial since sev-
eral studies have shown that they do not necessarily
correlate well with clinical outcome [26, 27, 30-32]
and may not provide sufficient information regard-
ing vascular injuries to be useful [23, 33]. However,
Federle et al. studied this issue and found that CT
can effectively recognize vascular injury and active
extravasation from splenic arterial branches [18].
In 2000, Shan mug an ath an et al. evaluated the
potential role of contrast-enhanced spiral CT in pre-
dicting the need for splenic angiography and embo-
lization by correlating them with results from subse-
quent splenic angiograms [19]. In their study, contrast
extravasation at CT was highly predictive of the need
for embolization, regardless of the CT grade of injury.
The presence of a pseudoaneurysm or arteriovenous
fistulas on CT, both of which are seen as focal areas
of high attenuation, was a less sensitive finding, with
only 58% of patients with these CT findings requir-
ing embolization or splenectomy. The angiograms
of the remaining 42% of patients with CT findings
suggestive of a pseudoaneurysm or arteriovenous
fistula did not reveal any focal vascular abnormali-
ties. These false-positive CT findings were attributed
to islands of enhancing splenic parenchyma sur-
rounded by low- attenuating splenic lacerations or
contusions and intact intiasplenic vessels traversing
parenchymal lacerations simulating hemorrhage sur-
rounding a focal pseudoaneurysm [19]. The finding
of a splenic vascular lesion on contrast- enhanced
spiral CT was 83% sensitive in predicting the need
for splenic angiography and subsequent embolization
or surgery. Using this approach, 94% of patients were
successfully selected at presentation for conservative
management. This study demonstrated thattheuseof
contrast- enhanced spiral CT and splenic angiography
improves early diagnosis and potentially increases [he
number of patients with blunt splenic injuries who are
treated successfully without surgery.
4.1.3.2
Diagnostic Angiography
The role of diagnostic angiography in t
tion of patients experiencing blunt splei
il Solid Organ Trauma
Table 4.1. AAST Splenic Injury Scale
Grade Type of Injury D esc rip Lion
H em ;i :o:";":
Laceration
Hemato::\a
Laceration
H em ;i :o:";":
Laceration
Laceraiion
Subcapsular, <10% surface area
Capsular tear, < = 1 cm parenchymal depth
Subcapsular, :0-.~0% surface area, inlraparenchynul, <5 cm in chameter
1-3 cm parenchymal depth that ckvs not Involve a trabecular vessel
apsular, >50% surface area or rxpancjng; :up:ured subcapsular or
parenchymal hematoma; intjjparenchymal, >? cm or expanding
:>3 cm parenchyma! depth or involving Trabecina! vessels
li'.volvii'g segmental ■ u hilar vessels prod; cing maior devai
(>25% of the spleen)
Completely shattered spieen
Hilar "vascular injury that cevascularizes the spleen
remains controversial. While some believe that all
patients with splenic injuries should undergo diag-
nostic angiography, others tire more selective and
prefer angiography lor patients with high-grade
parenchymal injury, vascular injury, or a large
volume of hemoperitoneum on admission CT scan
[6, 16, 23, 33-35]. It has been well established that
selective splenic angiography is successful at iden-
tifying vascular injuries, with positive findings
including active extravasation of contrast and the
presence of a pseudoaneurysm [33, 36]. It is the
early work of Sclafani et al. and Hagiwara et al.
that supports the angiographic evaluation of stable
patients with CT evidence of splenic injury [23, 33].
A positive angiogram is a strong predictor of nonop-
erative failure, necessitating the use of embolization
or surgery to allow for continued splenic viability
[1, 23, 33, 37-39]. Conversely, a negative angiogram
can successfully predict the success of observation
for these patients [33, 39].
However, others consider the use of angiogra-
phy in all patients with documei
is aggressive. Sclafani et al,
incidence of negative angiogra
lation [39]. Dent et al. recommend angiography
for patients with persistent tachycardia despite
fluid resuscitation, splenic vascular blush on CT,
severe splenic injury on CT, or decreasing hema-
tocrit that cannot be explained [40]. Using these
criteria, angiography was only necessary in 7% of
patients with blunt splenic injury and ultimately,
the success of nonoperative management was sim-
ilar to studies in which there was more liberal use
of angiography. Similarly. Lit: et al. argue against
the use of routine angiography since most patients
with blunt splenic injury can be successfully man-
aged by bed rest and observation [6, 7]. These
I splenic injury
ported a 70%
indings therefore need to be considered when
xposing patients to the inherent risks and cost of
ngiography [12].
4.1.4
Splenic Artery Embolization
The use of splenic artery embolization was origi-
nally described in 1973 in patients with hypersplen-
ism [41]. In 1981, Sclafani first reported the splenic
artery infusion of Pitressin, Gelfoam pledget embo-
lization, and coil occlusion of the proximal splenic
artery to treat splenic injury [36]. Since that time,
the findings of many studies have supported the use
of splenic artery embolization in patients managed
nonoperatively after blunt splenic trauma [2, 12, 19,
23, 33, 37, 39]. In general, embolization is reserved
for patients with documented vascular injury at
the time of diagnostic a ngiography, but the success
and ease of performing this procedure has led some
to utilize embolization in all patients with higher
grade injuries [2].
4.1.4.1
Technique
It must be stated that the goal of embolization in the
setting of splenic trauma is to reduce arterial flow
to the spleen so that hemostasis can take place at
the site of arterial injury. However, the importance
of maintaining splenic viability must not be forgot-
ten and therefore, continued perfusion of splenic
parenchyma from collateral vessels must also be
maintained during a successful embolization pro-
cedure.
C-. Siskin ;i:id 1. L.olz;i:uin
Technically, an abdominal aortogram is recc
mended prior to selective splenic artery catheteri
tion in order to visualize the exact point of origii
the splenic artery and to demonstrate the
or absence of variant anatomy. Most interventional-
ists then favor either a superselective approach with
distal embolization of the injured splenic artery
branches, or a relatively nonselective approach
with proximal embolization of the main splenic
artery, utilizing the angiographic appearance of the
splenic vasculature to make that decision. While
one can certainly make the argument that patients
with active branch vessel extravasation should have
clinical signs that should have necessitated imme-
diate surgery, the expanding use of angiography
and embolization at our institution frequently puts
us in the position of treating patients that seem to
require distal embolization for adequate treatment.
In these patients, it often makes intuitive sense to
select and embolize the injured branch vessels, a
feat made easier by advances in microcatheter and
microcoil technology [6]. In these patients, however,
consideration must be given to the balance between
superselective control of bleeding, the fluoroscopy
exposure time required for selective catheterization,
and the volume of splenic parenchyma put at risk for
ischemia and subsequent infarction (Fig. 4.1).
An alternative to superselective catheterization
of splenic artery branches is the use of proximal
splenic artery embolization [23, 33, 39]. In this
technique, the main splenic artery is embolized,
beyond the origin of the dorsal pancreatic artery
but proximal to the splenic hilum, with appro-
priately sized coils [33]. The reason behind this
technique is to decrease perfusion pressure to the
spleen while maintaining the ability of the spleen
to receive arterial inflow from collateral vessels,
including gastric, omental, and pancreatic vessels
[1,42]. Therefore, the splenic artery should be mea-
sured prior to introducing coils and care should be
taken to use coils that are large enough so that they
do not migrate into the hilum of the spleen since
the risk of splenic infarction,
of splenic perfusion was dem-
onstrated by Hagiwara et al. who demonstrated
preservation of splenic function by arteriography
and scintigraphy in patients who underwent proxi-
mal splenic artery embolization [23].
Patients with multiple vascular injuries are can-
didates for either proximal coil embolization or
combined therapy, which utilizes selective catheter-
ization and embolization of the most significantly
injured vessels followed by proximal coil emboliza-
tion [2]. In these patients, distal embolization since
this may require extensive fluoroscopic exposure
times to catheterize multiple small vessels with
subsequent infarction of too large a percentage of
splenic parenchyma. Haan et al. found no differ-
ence in failure rate when proximal embolization
was compared with more selective, distal emboliza-
tion. Interestingly, however, the largest failure rate
was found when both techniques were utilized in
Fig 4.1. a Selective spit
b Selective splenic an
splenic parenchyma
'sm .iiiiii":g fioia ;ii": upper po.e airnjiii ;'.:ie: Mi::': trauma.
pole briiadi of the splenLi" ;i:rciv supplying the injured
Visceral and Abdominal Solid Organ Trauma
the same patient, possibly due to the fact that thet
patients had the most severe injuries [2].
4.1.4.2
Results
Sclafani et al. were the first to report that the use
of splenic angiography and embolization expanded
the number of patients that could be managed non-
surgically [33]. In 1995, Sclafani et al. reported
a nonoperative success rate of 83%, with a splenic
salvage rate of 88% by performing angiography
on every patient with a splenic injury who did not
require urgent operation and proximally emboliz-
ing the main splenic artery of the 40% of patients
who had evidence of splenic vascular injury on angi-
ography [39]. Hagi war a etal.embolized 15 patients
due to extravasation within or beyond the splenic
parenchyma or disruption of terminal arteries with-
out extravasation [23]. In this study, it was noted
that patients requiring embolizing required larger
volumes of fluid for resuscitation than those who
were not embolized, implying that the angiographic
findings indicating the need for embolization cor-
related with a greater degree of hemodynamic insta-
bility at presentation, which may therefore be an
additional indication for embolization. In addition,
the CT grades for patients who did not undergo
embolization were significantly lower than those for
patients who were embolized.
In 1998, Davis et al. evaluated their experience
with 524 consecutive patients with blunt splenic
injury over a4 J ,■> year period [37]. A focal area of high
attenuation on CT, confirmed with angiography to
represent a pseudoaneurysm, was seen in 26 patients;
20 of these patients were successfully embolized and
did not require further surgery while 6 patients were
not embolized due to either free arterial extravasa-
tion, early filling of the splenic vein due to a traumatic
AV fistula, and multiple pseudoaneurysms. Given the
fact that the appearance of some pseudoaneurysms
will be delayed, Davis et al. emphasized the impor-
tance of obtaining follow-up CT scans inpatients that
are being managed nonoperativeiv [37].
HAANetal. [12] more recently reported their expe-
rience with the use of angiography in stable patients
with CT-proven blunt splenic injury. In their series,
352 patients presented after blunt splenic trauma
with 64% requiring immediate surgery. The remain-
ing 36% of patients underwent splenic angiography.
Patients with negative angiograms were observed.
Embolization was performed in 32% of those under-
going angiography due to positive findings includ-
ing contrast extravasation, arteriovenous fistula, or
pseudoaneurysm. Of these, 8% required laparotomy
(2 for bleeding and 1 for abscess formation), for a
splenic salvage rate of 92%, despite the presence of
high-grade injuries in many of these patients.
Sekikawa et al. reported on factors that support
use of anonoperative approach using splenic artery
embolization [34]. They found that injury severity
score and shock index had no significant correlation
with outcome, implying that more severe injuries
do not necessarily predict failure of nonoperative
management with embolization. However, hemody-
namic instability (as evidenced by low hemoglobin,
low hematocrit, and low blood pressure) was associ-
ated with a poor clinicaloutcome after embolization.
Based on their data, a patient's age, in addition to the
presence of head or solid abdominal organ injury in
hemodynamically stable patients, should not pre-
clude the use of embolization although concomitant
pelvic injury was associated with a poor clinicalout-
come. Importantly, the time interval from injury to
arrival at the hospital and from arrival at the hospi-
tal to the start of the embolization procedure did not
significantly affect clinical outcome.
The experience of Haan et al. [12] confirms that
embolization improved splenic salvage rates for all
CT grades of injury, including grades 3-5. This was
true even with patients that were at least as severely
injured based on transfusion requirements, injury
severity score, length of stay, and ICU stay [12]. Their
data also offers additional support for the use of
embolization in patients with concomitant neuro-
logic injury, stating thai angiographv may be asso-
ciated with a statistically and clinically significant
decrease in mortality in patients with neurologic
injury when compared with operative therapy [12].
They went on to theorize that patients with neuro-
logic injury pursuing nonoperative management are
spared the risk of intraoperative or postoperative
hypotension. It has been stated that a single episode
of hypotension can increase neurologic mortality by
50-80% and intraoperative hypotension during sple-
nectomy is a frequent occurrence [12, 43]. Therefore,
utilizing angiography and embolization for these
patients potentially avoids this risk and may lead to
less secondary brain injury and lower mortality.
Haan et al. also reported the results of a multi-
center review of patients undergoing splenic artery
embolization for splenic trauma and this represents
the largest collection of splenic artery emboliza-
tion patients studied to date [2]. In this review, 140
patients undergoing splenic artery embolization at
ind 1. GolzLiriiUi
one of four institutions over a 5-year period were
retrospectively evaluated. They found that splenic
artery embolization is used for patients with high-
grade splenic injury with mi average grade of injury
of 3.5 in this series. Despite significant injury sever-
ity, splenic salvage of patients selected for emboliza-
tion was 87% in this series. This series documented
a failure rate for embolization of 10% with 17% of
patients demonstrating active contrast extravasa-
tion failing [2]. In this series, patients with AV fis-
tulae had the worst outcome and they hypothesized
that proximal coil embolization may not be enough
in these patients since the drop in perfusion pressure
may not be sufficient to provide hemostasis [2]. This
same multicenter center found a 19% rate of major
complications and 23% rate of minor complications.
Taking overlap of these patients into account, there
was a 32% complication rate. The most common
complication, seen in 60% of patients, was blood
loss or continued blood loss. True infection is rare
but significant splenic induction was common, with
a rate of 20-27% [2]. The vast majority of patients
experiencing splenic infarction, however, were
asymptomatic and able to continue being managed
nonoperatively.
4.1.4.3
Post-Em bo lization Follow-up
Following nonoperative management and splenic
artery embolization for blunt splenic trauma, most
patients typically require continued observation in
a monitored setting since there continues to be a
risk of bleeding or sepsis. It is generally accepted
that these patients should be followed with abdom-
inal CT until resolution of the injury is seen [44].
Killeen et al. performed a retrospective study
to evaluate the CT findings after splenic artery
embolization in 53 patients [1]. They found that
splenic infarcts described as small, multiple, and
peripheral were seen in 63% of patients after a
proximal splenic embolization while infarcts were
seen in 100% of patients after a distal embolization.
The infarcts seen after both proximal and distal
embolization tend to resolve without sequelae [1].
In these patients, the infarcts tended to be larger,
single, and located just distal to the embolization
material. Gas within splenic parenchyma was seen
in only 13% of patients but was shown to more
commonly occur when Gelfoam was used as the
embolization agent [1]. The presence of gas, how-
g because it is difficult to exclude
a splenic abscess clinically or based on CT find-
ings [1].
Haan et al. further explored the CT finding of
air within areas of infarction after splenic artery
embolization [45]. They found that air in areas of
splenic infarction was associated with infection in
only 17% of patients but that this rate increased
to 33% in symptomatic patients [45]. Clearly, this
implies that air is not pathognomonic of infection
and that further investigation must be performed in
these patients prior to splenectomy. While asymp-
tomatic patients can likely be observed, patients
with symptoms and a minimal amount of air should
be treated with antipyretics. Aspiration and percu-
taneous drainage should be considered, as should
splenectomy, in patients with large areas of infarct
air and/or severe symptoms [45].
Hepatic Artery Embolization
4.2.1
Patient Selection
r similar to how splenic injuries are being
treated, there has been a trend in recent years towards
the nonoperative management of hepatic injuries,
especially in hemodynamic ally stable patients [46-
52]. Given its large size, the liver is obviously suscep-
tible to injury in association with blunt trauma. In
addition, iatrogenic trauma due to biopsies and other
procedures can lead to vascular injury potentially
requiring embolization as treatment. The vascular
injuries seen are similar to those seen with other
solid organ injury', including arterial laceration with
extravasation in addition to pseudoaneurysm forma-
tion but unique to the liver is the potential for fistulas
to develop between any of the intrahepatic vascular
structures and the biliary system.
Almost two decades ago, Meyer et al. recom-
mended the following criteria for nonsurgical
management of blunt liver trauma: hemodynamic
stability, CT scans showing simple parenchymal lac-
erations or intrahepatic hematoma, <250 cc of free
intraperitoneal blood, no other significant intraab-
dominal injury, and availability of close monitor-
ing [53]. The absence of associated injury must be
determined with the use of abdominal CT, since it
has been estimated that 35% ol patients may have
associated injuries requiring surgery [52]. When
these criteria are utilized, it has been estimated that
il Solid Organ Trauma
80-90% of all blunt liver injuries may be manage
without Laparotomy [54, 55], Certainly, emboliz;
tion and other interventional radiologic procedure
have contributed to this success [56].
4.2.2
Diagnosis
For years, contrast enhanced CT has been the imag-
ing technique of choice to evaluate hemodynami-
cally stable patients with blunt abdominal trauma.
It is considered a reliable way to detect hepatic inju-
ries and has therefore been used to grade injuries
(Table 4.2) and assess whether surgery or more con-
servative treatment will be necessary and successful
[57]. Importantly, the severity of hepatic injuries may
be underestimated on CT scans but the decision to
pursue nonoperative management has been shown to
not be dependent on the grade of liver injury [50, 54].
Successful management of lieinoolvnamtcallY stable
patients of all grades has been demonstrated [55,
59-61]. In general, if the patient is considered stable
after resuscitation and the hepatic injury is either
isolated or in combination '.villi other injuries that do
not themselves require surgery, then a nonoperative
approach to management is utilized [61].
4.2.3.1
Technique
Flush aortography i'< rvpk ally required before selec-
tive catheterization of the common hepatic artery,
similar to that required before splenic artery cath-
eterization. Even more so in the case of the hepatic
arterial circulation is the potential for variant
anatomy. Once the origin of the hepatic artery has
been identified, selective catheterization can be per-
formed. Whereas the goal in splenic artery embo-
lization is to potentially embolize proximally and
preserve flow to the spleen via collateral circulation,
a more distal and selective embolization is often the
goal when it comes to the treatment of hepatic arte-
rial injury. However, in some situation, the embo-
lization of the right or left hepatic artery might be
necessary. In those situations, Gelfoam emboliza-
tion can be performed with larger particles and
torpedoes (Fig. 4.2). Fortunately, the contribution
of the portal vein to the hepatic circulation enables
the liver parenchyma to tolerate hepatic arterial
embolization without significant ischemic injury.
Given the more distal nature of this embolization,
microcatheters and microcoils are often required
for these procedures, although success has been
reported using a variety of embolic agents including
Gelfoam, polyvinyl alcohol, and coils (Fig. 4.2).
4.2.3
Hepatic Artery Embolization
Embolization has been shown to be an effective
treatment to offer patients that respond to resusci-
tation but rapidly become unstable if resuscitation is
withdrawn [61]. While it certainly would be appro-
priate to operate on these patients, an understand-
able desire to avoid the potential complications
associated with surgeryhas increased the utilization
of embolization in this setting [61].
4.2.3.2
Results
Reports dating back to 1977 have demonstrated the
effectiveness of emlxiliz.it ion for patients experienc-
ing blunt hepatic trauma [62-65]. Hagiwara et al.
[66] demonstrated that nonsurgical management
of Grade III or IV us ins ansiosrapiiy and Gelfoam
embolization was successful in allpatients.Inalater
study, Hagiwara et al. [67] prospectively evaluated
Table 4.2. Mirvis Computed Tomographic Scan Hepatic imury Severity Scale For Blunt Hepatic
Trauma [69]
■Capsular avulsion; superficial lacerationis) ■■■.'] cm d^ep. or sr-bcapsuhr hematoma
<1 cm maximal llucknrss, pei i porta I bio cm : in eking only
r 1 ;; renchym.i I laceration! s! 1 -3 cm deep: cea:ra' o: subcapsular hematoma(s) 1-3 err
diameter
Lacerationis! >3 era deep: cemral or subcapsular hematoma !3! >3 cm la diameter
Massiw ceiili'jl/s'.'.bcjpsiila:' hematoma >I0 c:v. in diameter, lobar us
ir devascul.ai/ahon
G. Siskin and J. Gol:
Fig. -1 .2 a I. 41 year- dd ::;:.a with abdominal -.in.:', pelvis trauma, n Contrast-enhanced CT of ihe upper abdomen oemonsliates
a hematoma tin," ,r.t.v c bleeding : r r . \ > 1 1 : .11 the 1 igbi hepatii oaivi'.ohvn'.a. b Cell .;■." trunk angiogram shi ws ;l'.e :'.i iei i,i. .tS [■:■:'.
i slip ft iifciin) with early venous drainage i.bi,i:k .n :■■:■•■. 1. c Selective mioiooiithete: plaoement in [he feeding artery and er.ibo liga-
tion with coj.s is performed. Angiogram ."em- 'lis I iir.es die persistence of extravasation ianp n i. d Hryaiie angiogram, oblique
view, after embolization of another fertimg artery deirr 'itsi rates ihe extravasation iiinoiij. e 10 minutes aflrr einnoiizatio:;,
there ivas a rr-ers! stent extravasation from iiepati-." artery. 7 lie right heratic arteiy is their emhohzed nsn'.g '..edoum toipedoes.
f Contrast enhanced CT obtained 14 hours a iter embolization shows no more bleeding
patients with Grade III-V injury who were treated hemodynnmiaUly stable patients in whom contrast-
with angiography and embolization. They con- enhanced CT shows extravasation of contrast, even
eluded that embolization should be used to manage when the injury is severe. Since embolization obvi-
lii] Solid Organ Trauma
ously has no effect on bleeding from juxtahepatic
venous injuries, Hagiwara et al. advocate the use
of surgery in these patients. They found that all
patients with juxtahepatic venous injury required
>2, 000 ml/hour of fluid for resuscitation. There-
fore, they consider the combination of a Grade IV
or V lesion and fluid requirements >2,000 ml/hour
to maintain normotension an absolute indication
for surgery. The success of hepatic artery emboliza-
tion was also demonstrated by Pachter et al. [59],
Carillo et al. [60], Mohr et al. [68], and Sugimoto
et al. [69], who successfully performed embolization
on patients after blunt liver trauma who were con-
sidered stable after resuscitation. Ciraulo etal. [61]
evaluated their experience utilizing embolization in
patients with severe hepatic injury and found that
embolization with Geltoam and coils was success-
ful in patient whose stability was maintained only
by aggressive continuous resuscitation. In these
patients, embolization resulted in a reduction from
continuous resuscitation to maintenance fluids,
which inferred an improvement in hemodynamic
stability.
4.2.3.3
Post-Embolization Follow-up
Once the decision has been made to pursue nonop-
erative management for patients with blunt hepatic
trauma, an additional decision concerning follow
up imaging needs to be made as well. Typically,
follow-up CT scans have been performed to detect
complications, to document healing of the liver
injury, and to guide patients' activity restrictions
[54]. However, some have advocated a selective
approach to the performance of follow-up CT scans
[70]. Ciraulo et al. [71] reviewed their experience
in 95 patients with blunt hepatic injury to determine
if follow-up scan altered management or discharge
decisions. They found that follow-up CT scans did
not alter the decision to discharge stable patients
with Grade I— I II injuries. Cuff et al. [54], agreed
with this finding and concluded that follow-up
CT scans may not always be necessary in patients
being treated nonoperatively. In their study, only
two patients were found to have significant CT find-
ings during their hospitalization: one patient had
a bile leak and biloma while another patient had a
hepatic artery to portal vein fistula. Both of these
patients had Grade IV injuries and both continued
to be managed nonoperatively. Based on this study,
Cuff et al. concluded that follow-up CT scans are
y in stable patients with Grade I, II, or
III injuries. Instead, the need for follow-up imaging
should depend on the results of serial clinical evalu-
ations with CT scans indicated in stable patients
with persistent abdominal pain, sudden change
in clinical examination, unexplained tachycardia,
fever, jaundice, or decreasing hemoglobin [54].
Complications alter embolization include delayed
hemorrhage, hepatic necrosis, infection/sepsis, and
biliary fistula. They manifest with abnormal physi-
cal findings, elevated liver function tests, or find-
ings on imaging studies such as ultrasound or CT
(Fig. 4.3) [56, 61, 68]. Fever is common after hepatic
artery embolization, occurring in as many as 69-
100% of patients [60, 68]. Hagiwara et al. found
bilomas in 4 of 54 patients and these were associ-
ated with pseudoaneurysms in 3 of these 4 patients
[66]. They propose that the presence of bile delays
healing of liver injury and causes an inflamma-
tory reaction that can ultimately lead to rupture
of blood vessels and delayed hemorrhage. Mohr et
al. reported on five patients with hepatic necrosis
after embolization, all of whom required operative
debridement or resection with one of these patients
ultimately dying after the procedure [68]. 80% of
the patients with hepatic necrosis also experience
infarction of the gallbladder that required chole-
cystectomy. These patients required embolization
of right hepatic artery branches during their initial
procedure. Mohr et al. also noted a 2.i% incidence of
biliary leakage alter emboli zation and these patients
typically required biliary drainage lor a median of
1 month. In total, Mohr found that 21% of patients
required a return to the operating room for hepatic
complications while Knudson et al. reported a rate
of 18% [72]. Of note, Carrillo demonstrated the
importance of other interventional radiologic tech-
niques such as percutaneous drainage and biliary
drainage in managing several of these complica-
tions, contributing to the continued nonoperative
management of these patients [60].
Renal Artery Embolization
4.3.1
Patient Selection
As stated throughout this chapter, there is a continu-
ing movement towards nonoperative management
for patients experiencing significant solid organ
ind 1. Golzanan
Fig. 4.3. CT scan o: lire liver 1 week ,ii':e: lirpatie artery embo-
lization as treat mm; for .; Liaun^ili." liver I Liberation. The CT
reveals a subcapsular fluid ja Ilea ion and an inliapjienihy-
raal, air-containing abbess in die righl lobe of the liver
parenchyma, grading the severity of injury [84]
and confirming the presence of active bleeding and
other peritoneal or retroperitoneal injuries [85]. It is
effective at diagnosing injuries ranging from contu-
sions and hematomas to shattered kidneys (Fig. 4.4)
or avulsion of the renal ped icle [86, 87]. CT find ings
indicative of an arterial occlusion include a lack of
renal enhancement in the presence of a normal renal
contour, rim enhancement, central hematoma, and
abrupt cut-off of an enhancing renal artery [88].
Segmental arterial injury should be suspected when
an area of decreased parenchymal enhancement
corresponds to an area perfused by one of the seg-
mental arteries [83].
4.3.3
Renal Artery Embolization
injury after trauma. This has been seen concerning
the nonoperative management for patients experi-
encing renal vascular trauma as well [73]. While
some believe that surgical exploration is warranted
because it ultimately improves the nephrectomy
rate [73-75], other believe that nonoperative man-
agement is more effective at preventing the need
for nephrectomy [76-80]. Accepted indications for
surgery include avulsion of the renal pelvis, inju-
ries to the vascular pedicle, and life-threatening
hemodynamic instability while embolization can
be considered in patients with continuous hema-
turia or massive hemorrhage due to renal vascular
injury [81].
4.3.2
Diagnosis of Renal Vascular Injury
The diagnosis of renovascular injury may be diffi-
cult in some patients, especially because hematuria,
which is thought to be present in most patients, can
be absent in up to 33% of patients with injuries to the
renal artery [82]. This is why imaging is often nec-
essary in these patients. In addition, patients with
renal vascular injuries typically have other signifi-
cant intraperitoneal and retroperitoneal injury [83],
supporting the need for imaging evaluation. These
other injuries can lead to the elevated injury sever-
ity scores and increased transfusion requirements
often seen in these patients [83].
At the present time, contrast-enhanced spiral CT
is the best imaging modality tin assessing the renal
4.3.3.1
Technique
As has been the case with the embolization of other
solid organs as described in this chapter, it is rec-
ommended that these procedures start with a non-
selective abdominal aortogram. Variations in the
number of arteries supplying one or both kidneys
are numerous and therefore must be documented
before attempts at selective catheterization are
made. In addition, the angle of origin between the
abdominal aorta and renal arteries will help guide
catheter selection for catheterization. Aortography
is also important tortile out traumatic disruption or
dissection of the renal artery before selective cath-
eterization is attempted. Embolization is typically
performed as distal as possible, or as close as possi-
ble to the site of arterial injury, in order to minimize
the amount of devascularized renal parenchyma
after the procedure. This typically requires the use
of microcatheters and microcoils (Fig. 4.4).
4.3.3.2
Results
Renal vascular injuries, caused by both blunt and
penetrating trauma, can be effectively treated with
arterial embolization from a supers elective catheter
position, resulting in organ salvage and tissue pres-
89-92]. Hagiwara et al. evaluated 46
patients with evidence of renal injury on
inal CT [93]. Twenty-one of these patients
ide 3 or higher injuries and underwent angi-
*$<kV- A
■
a-g. 22 year-old female with a car accident, a Enhanced CT dem-
• retroperitoneal Kind collection and partial light kidney fracture
iiTJ iow). b Slice cauda! to image a shows a hyprrden.se retropei iloneal
b!ee-.i tijt: and the transecied srginent .if the right kidney thai is taking tip
contrast : ni row j. 1 1 relayed piiase of an aoitogram demonstrate normal
iiTphiogiam ii! the left side but a small nephrogi am in the rig:: I kidney
fiTi'iiiu'). (I Catheterization of The rem: I arterv feeding the superior part of
lhe right kidney with norma, nephrogram, e Catheterization of the renal
branch of transected segment of the right kirin.ev demonstrates an arte-
rial transection ; biii.:k .incur j and an arte: ial extravasation i wit ire iirmu).
f Angiogram obtained after selective coil embolization proximal to the
transected vessels. Note the opacihcation of the pyexcakcea! system o:' the
superior fragment ■ ■: right kidney (,-p ere ■.■. j.g Enhanced CT afle: emboliza-
tion shows no extravasation with stagnation o:' contrast from emboliza-
tion procedure in the retroperitoneal collection (arrow)
0. Siskin ;i:id 1. i.".olz;i:;an
Table 4.3. Organ Injury Score lor Blunt Renal Trauma*
Grade Type [ icsirsj.it ion of Trsuinu
1 Contusion Hermit'.:.! is;, imaging studies normal
Hematoma Subc, , .. l su..i< hematoma (nonexpanding)
2 Hematoma Periien-.il liema:om:; (contained, noneNpanomgi
Laceration Cortical laceration (<l cm) without urinary
3 Hematoma Perirenal hem a: cm:: (contained, nonexpandmgi
Laceration Cortico:-:edullarv laceration detpei I linn 1 cm without
4 Laceration Cortici'iiiedulkuy laceration deeper I:".;";:: : cm with collecting system injury
Vascular Injury to main renal artery or vein w;lh conia.uied Hemo: rhage
5 Laceration Comp!e-elr s!"ia:lere.:. .-i.dney, ureleropelviceal avulsion
Vascular Avulsion of renal hik.im. ,".evascula:i^:ng ^.idnev
. no:re\pand:ng perirenal hcina.loma
ntlie.
n for the Surgery of Trauma (AAST) [99].
ography. One patient had venous extravasation
and ultimately required surgery; this was the only
patient in this series who required surgery. Eight
patients demonstrated arterial extravasation and
were treated successfully with embolization. Suc-
cess with embolization has been demonstrated in
hemodynamics lly unstable patients presenting with
gross hematuria, active bleeding, and symptoms of
shock. These patients are at risk for significant mor-
bidity and mortality with surgery supporting the
use of embolization during their care. It has been
shown that in these patients, embolization can help
control bleeding without nephrectomy [94].
Embolization is also well suited to patients that
are initially stable after trauma but develop delayed
bleeding over the course of days, weeks, or months
[86]. In these patients, the delayed bleeding is most
likely due to the formation of a traumatic pseudoa-
neurysm or arteriovenous fistula, which is more
common in patients experiencing penetrating
trauma than blunt trauma [95]. Pseudoaneurysms
form after blunt trauma due to rapid deceleration-
induced injuries to renal arteries [96, 97]. As they
form, pseudoaneurysms can contact the collecting
system, which can lead to the delayed hematuria
often seen in these patients [95]. These pseudoan-
eurysms can be successfully treated with selective
embolization.
4.3.3.3
Post-EmboEization Folio 1
-up
There are potential complications associated with
the surgical management of patients with renal vas-
cular injuries. These include azotemia and persistent
hypertension, which may possibly require nephrec-
tomy for management [83, 98, 99]. At the present
time, significant and persistent hype
not been reported after superselective renal embo-
lization [86]. The post-embolization syndrome that
is commonly seen after solid organ embolization for
other indications and consists of pain, leukocytosis,
and fever, is uncommon after selective renal artery
embolization in the setting of trauma [100].
Cookbook
Splenic Artery Embolization
• Proximal Embolization: In the absence of active
contrast extravasation, the splenic artery is
proximally embolized. We typically utilize
either a 5F Cobra catheter or a 5F Omni-2 cath-
eter to catheterize the celiac axis. Depending
on the tortuosity of the vessel, we then either
use the Cobra catheter or a microcatheter with
a 0.021" inner luminal diameter for more selec-
tive catheterization. Once the catheter is in
place, just distal to the dorsal pancreatic artery,
coils are deposited. The size of the coils chosen
depends on the size of the vessel.
• Distal Embolization: If active extravasation is
present, we find it desirable to selectively cath-
eterize and embolize the injured branch vessel.
This requires the use of a microcatheter (0.021"
inner luminal dia.) and appropriate guidewire.
Once the microcatheter is as distal as it can be,
microcoils (either straight or helical, depend-
ing on vessel size) are used for embolization.
Hepatic and Renal Artery Embolization
• In patients with hepatic or renal arterial injury,
our goal is to embolize as distally as possible,
with the intent of sparing as much parenchyma
as possible. This typically requires the use of
microcatheter and microcoils as above.
il Solid Organ Trauma
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5 Embolization and Pelvic Trauma
Jeffrey J. Wong and Anne C. Robi
iiili'O'.kiiiii.'i! .ii'.'.l Background 59
Penetrating vs Blunt Trauma 59
Causes and Epidemiology 59
Sou ['tis or" Bleeding: Arterial vs Veno
■;. Vlii
60
5.1.4 Why Not Surgery? 60
5.1.5 Role oi Interventional Radiology -0
5.2 Presentation 60
5.2.1 Shock/Active Hemorrhage 61
5.2.2 Pelvic Fracture & Plain AP Radiographs 61
5.3 Guiding/Directing Therapy
and the Laparotomy 61
5.3.1 Diagnostic Perilor.riil Aspiration, Ultrasound,
and Contrast-Enhanced CT 61
5.3.2 External Fixation 62
5.3.3 Laparotomy 62
5.4 Endovasciiln: Therapy 63
5.4.1 Access to Vessels 61
5.4.2 The Initial l-v^ic A; ;e: iogram and Further
Studies 63
5.4.3 Angiographic Appearance c\ Hemorrhage 64
5.4.4 Embolization Agents 64
5.4.5 What To Do If No Bleeding Is Seen?
The "Check" Arteriogram 66
5.5 Complications 66
5.6 Conclusion 67
Cookbook: 66
References 57
Introduction and Background
5.1.1
Penetrating vs Blunt Trauma
Like all traumatic inju
can be classified into e
Penetrating mechanisn
gunshot wounds biopsi
;s, trauma to the pelvis
ter penetrating or blunt.
such as stab wounds,
, or surgical or percuta-
J. J. Wong, MB ChB, BMedSc; A. C. Roberts, MD
University of California, Si;:'. I 'iegc Medical Center, Divi
Vascular and Interveiv.ioi'.a] Radiology, 200 West Arbor
San Diego, California, 92103-B756, USA
neous spine procedures, may directly injure pelvic
organs, nerves, or the blood vessels. Blunt trauma
exerts its effects through vessels being sheared
against fixed ligamentous structures and avulsion
of vessels attached to displaced bony pelvic struc-
tures. Pelvic fractures also damage adjacent pelvic
or retroperitoneal structures. The interventionist's
primary concerns are vascular injuries, notably
hemorrhage from the branches of the internal iliac
5.1.2
Causes and Epidemiology
Pelvic fractures account for 3% of all skeletal inju-
ries and are associated with a substantial mortality,
with reported figures varying from 5% to 60% [1-
21]. Mechanisms for pelvic fractures include motor
vehicle accidents (57%), pedestrians hit by motor
vehicles (18%), motorcycle accidents (9%), falls (9%),
crush injuries (4%), and sports/recreational mecha-
nisms (3%) [22]. Pelvic fractures are grouped based
on the direction of the causative force. These forces
include lateral compression, anteroposterior com-
pression, vertical shear, and combinations of these
three [23]. Most injuries to the infrarenal aorta are
caused by seat belts compressing the lower abdomen
in the anteroposterior aspect during car accidents.
A closed stable fracture with stable vital signs
offers the best prognosis, while patients with an
open fracture and hemodynamic instability have
a higher mortality. This latter subgroup only rep-
resents l%-2% of all pelvic injuries seen in Level 1
trauma centers [24] but no other skeletal injury car-
ries such a high mortality rate.
As hemorrhage is the most common treatable
cause of death in this population of patients, it is
imperative that vascular injuries are treated swiftly
ively. Clarke et al. [25] suggested that the
by 1% every 3 minutes
hemodynamically unstable.
risk of mortality
that a patient ren
:. Wong ;ind A.G.Roberts
5.1.3
Sources of Bleeding:
Arterial vs Venous vs Marrow
Direct bleeding from the fractui
bones or from injured pelvic
can cause pelvic bleeding. The anatomy of the ret-
roperitoneum and its contents provides a natural
tamponading effect on the fragile venous plexus
adjacent to the pelvic bones and osseous bleeding.
However, in the event of pelvic disruption and an
unstable pelvic fracture, this tamponading effect is
lost. A 3-cm diastasis of the symphysis pubis will
increase the potential volume of the pelvis from 4
liters to 8 liters [26]. The lack of valves between the
inferior vena cava and the pelvic veins allows for
potential catastrophic blood loss if the retroperi-
toneum is violated. Pelvic fixation, be it invasive
or noninvasive, will re-establish and maintain the
tamponading effect, thus controlling bleeding from
the venous and osseous structures. A dog model has
been used to show that ligation of multiple pelvic
arteries had no effect on the pelvic venous pres-
sure [27]. Because the source of pelvic hemorrhage
is from venous structures 80%-90% of the time
[28,29], there is a strong argument for starting with
pelvic fixation and intrapelvic compression. Clini-
cally, it is not possible to determine the source of
pelvic hemorrhage without the aid of radiographic
studies. Thus there remains much debate as to
whether a patient who has presumed pelvic hem-
orrhage undergoes angiography or pelvic fixation,
since fixation can only temporize small vessel
hemorrhage [28, 30]. If the bleeding source is arte-
rial, angiography and embolization is necessary.
Miller et al. [31] showed that if patients present with
hypotension from a pelvic fracture, poor response
to resuscitative efforts indicates the presence of
arterial bleeding in over 70% of patients. Mean-
while, responsive patients are unlikely to have arte-
rial bleeding, with a negative predictive value of
100%.
pathways, as well as large hematomas obscuring
the surgical field further complicate the technical
aspect of surgical control of arterial hemorrhage.
An obscured field of view increases the likelihood
of complications such as nerve injury. The primary
operative option for controlling pelvic bleeding
consists of packing and correction of coagulopathy.
Temporary aortic clamping has been suggested to
improve access to the site of bleeding [32].
5.1. 5
Role of Interventional Radiology
The interventional radiologist has become the cen-
tral figure in treating traumatic pelvic and retro-
peritoneal arterial hemorrhage, and with impressive
results. Angiographic embolization has a success rate
between 85% and 100% when bleeding sites can be
identified [33, 34]. The first-line therapy for an unsta-
ble patient with a pelvic tract ure should be immediate
angiographic evaluation and embolization.
Presentation
All trauma patients should be initially assessed fol-
lowing standard Advanced Trauma Life Support
(ATLS) guidelines, the details of which cannot be
covered in this text. However, as interventional
radiologists, we are most concerned with signs and
symptoms that will raise our suspicion of pelvic
fractures and hemodynamic compromise. As the
presentation of patients with life-threatening hem-
orrhage can vary from exsanguinating shock to
subtle innocuous signs, a detailed knowledge of the
presentations of pelvic trauma is necessary.
5.2.1
Shock/Active Hemorrhage
5.1.4
Why Not Surgery?
Evidence ofshockconsists of hypotension, tachycardia
(pulse > 100 beats per min), tachypnea, cool exlremi
ties, low urine output, and a progressive decline in
cal approach to retroperitoneal bleed- the level of consciousness. A normal blond pressure
ing is not a treatment for retroperitoneal pelvic may be misleading in young patients, because the
bleeding. Dissection into the retroperitoneum and blood pressure may be maintained by a compensatory
pelvis results in the loss ot (lie internal compression increased heart rate. In these patients, hypotension
effect provided by adjacent anatomic structures, occurs only when this mechanism fails and usually
resulting in increased bleeding. The rich collateral indicates impending cardiovaskul > . •■! . •■■
Embolization and Pelvic Traum
The hemoglobin level is not a specific marker of
hemorrhage as, in the acute stages, the hemoglobin
or hematocrit is likely to be normal. A few hours
are required before extravascular flu ids equilibrate
with the blood and for laboratory values to reflect
blood loss. It is imperative to obtain two intrave-
nous accesses with large bore cannulas and start
an infusion of intravenous fluids as soon as pos-
sible. O-negative blood should be readily available,
and blood samples should be sent early for cross
Guiding/Directing Therapy and the
Laparotomy
Once the suspicion of pelvic hemorrhage has been
raised, one must systematically follow a protocol
that will ensure injuries and sources of bleeding
are addressed in order of gravity. Heetveld et al.
[39] published an evidence-based algorithm for the
management of hemodruainlcalh unstable pelvic
fracture patients (Table 5.2).
5.2.2
Pelvic Fracture & Plain AP Radiographs
The suspicion for a pelvic fracture should start with
a history of a high-energy impact such as a motor
vehicle accident or a fall from a substantial height.
Careful inspection may reveal leg length discrepan-
cies (Roux sign), flank ecchymosis (Grey-Turners
sign}, blood at the urethral meatus, rectal bleeding
and/or vaginal bleeding. Hematomas observed on
the proximal thigh superficial to the inguinal liga-
ment or over the perineum are also suggestive of
a pelvic fracture (Destot's sign). Tenderness with
gentle pressure on the iliac wings bilaterally also
supports the diagnosis of a pelvic fracture. Care
must be taken not to apply too much pressure as
this may aggravate hemorrhage in an as-yet-undi-
agnosed unstable fracture. Rectal examination may
reveal a high-riding prostate or a large hematoma
or palpable fracture line (Earle's sign). Examina-
tion of the lower limbs may also show neurovascular
deficits.
Most patients will usually have plain films of
the chest and pelvis, regardless of their hemody-
namic situation. Anteroposterior (AP) pelvic films,
although only 68% sensitive for diagnosing all frac-
tures [35], will reveal and define any large fractures
which would raise our suspicion of retroperitoneal
bleeding. It has been shown if an unstable fracture
pattern is seen or suspected, the probability of pelvic
arterialbleeding is approximately 52% [11, 14,34, 19,
21, 36, 37]. Niwa et al. [38] showed that AP pelvic
films can be useful in predicting hemorrhage sites
based on the location and severity of the fracture.
Interestingly, stable pelvic fractures have shown to
be more strongly associated with abdominal bleed-
ing rather than pelvic bleeding [21].
Kane's classification of pelvic radiograph's
helps to convey the gravity of the bony injury (See
Table 5.1).
5.3.1
Diagnostic Peritoneal Aspiration, Ultrasound,
and Contrast-Enhanced CT
The initial examination of the patient may elicit
signs of peritoneal irritation on abdominal pal-
pation. As the laboratory and plain film inves-
tigations fail to address the abdominal cavity,
these clinical signs will point the trauma team
to proceed with further investigations. An acute
abdomen in the setting of hemodynamic instabil-
ity should result in either a diagnostic peritoneal
lavage (DPL) or focused abdominal sonography for
trauma (FAST). These investigations will reveal
blood/free fluid in the abdominal cavity suggest-
ing intra-abdominal hemorrhage and, in the pres-
ence of hemodynamic instability may indicate the
need for a laparotomy.
It is not recommended that hemodynaiuieally
unstable patients undergo a computed tomography
(CT) scan. However, in those patients stable enough
to be transported, contrast-enhanced CT of the
abdomen and pelvis can help distinguish actively
extravasating contrast material from clotted blood
[40]and thus guide surgical or angiographic ther-
apy.
In the hemodynamically ualMe patient, CT is the
preferred method of investigation [41]. Cerva et al.
[42] in 1996 showed that using angiography as a gold
Table.". 1. Kjne's c]jss:i'li.":U'i::ii] of pelvii fruciine
K.ine's d.iisi- Pefinkion
Fracture of only 1 pelvic bor
Single breaks in the ring near the pubic sym-
physis or a sacroiliac joint
Double breaks in the ring
AiViahJjr fractures
'.. Wong 'in J A. G. Roberts
Table 5.2. Algorithm for the mana;
unstable pelvic fracture patients
caliy unstable patient with a pelvic fracture
Laparotomy
on catheter angiography. This posed a challenging
therapeutic dilemma. As she was hemodynamically
stable and there were no signs of hypovolemia, the
eventual decision was not to embolize. The patient
returned to the intensive care unit and did well.
5.3.2
External Fixation
:al. [39] suggest
i tamponading
i open surgical
e that may be
Following DPL or FAST, Heetveld e
using external fixation to provide
effect. Internal pelvic fixation is ar
procedure that consumes precious ti
better spent on laparotomy or angiography. Nonin-
vasive methods ol pelvic fixation include a pelvic
sling, pelvic binder, C-clamp, military anti-shock
trousers (MAST), and external fixation. The latter
two options are most relevant to the intervention-
ist because they impair access to the femoral arter-
ies [44]. A hole can be cut with scissors into the
upper edge of a pelvic binder to allow access into
standard, contrast enhanced CT was 85% specific,
84% sensitive and 90% accurate. This study used
10-mm collimation at 20-mm intervals. However,
a more recent study by Pereira et al. [43] found a
sensitivity of 90%, specificity of 99% and accuracy
of 98 with helical CT using 10-mm intervals with
a pitch of 1.0:1 to 1.5:1. They suggested its use as
a method for screening polytrauma patients with
pelvic fractures to accurately identify patients who
would benefit from emergent angiographic embo-
lization. It is important that patients who may be
going on to angiography not receive oral contrast
material that would interfere with the angiographic
evaluation.
With improving technology resulting in faster
image acquisition and higher-resolution images,
contrast-enhanced multi-detector CT has become
increasingly accurate and may even surpass conven-
tional angiography in sensitivity. In one study, four
hemodynamically stable patients exhibiting con-
trast extravasation on CT did not require emboliza-
tion during hospitalization [43]. An example of this
clinical scenario is seen in Fig. 5.1, which involved
a hemodynamic ally stable trauma patient with vis-
ible extravasation on CliCT which was undetectable
Following Heetveld et al.'s guidelines [39], if evi-
dence of intra-abdominal hemorrhage is found, a
laparotomy is indicated. As a general rule, intra-
abdominal hemorrhage takes priority over retroper-
itoneal pelvic bleeding. So, in the face of detected
abdominal free fluid, a pelvic fracture and hemody-
namic compromise or catastrophic exsanguination,
a laparotomy is first-line therapy. If, after achiev-
ing abdominal hemostasis [inn a- abdominal repair],
retroperitoneal pelvic bleeding is detected and
hemodynamic instability continues pelvic packing
with large sponges should be performed and the
patient be taken to angiography. Eastridge et al.
[21], however, suggest considering angiography over
laparotomy with unstable pelvic fractures, despite
the presence of hemoperitoneum.
Ligation of the internal iliac artery has been
shown not to lead to satisfactory reduction in bleed-
ing [45-48]. This is thought to be due to the rich col-
lateral blood supply to the pelvic region and the loss
of the tamponading effect of the retroperitoneum.
Following surgery, angiography is warranted if the
patient requires transfusions of 4 units or greater in
24 hours or hemodynamic instability persists [36,
49].
Embolization and Pelvic Trauma
Fig5.1a,b. Fl1 : :v.vt.'.:-..aI lei'.o'.e v.;.< .hi lesuajriec c.r.vei ;:'.\v.|yec. in :■. roiid r i l : . : :: ■_" accidem Ij .ivelma lit 55 mpri. She wiis
hemO';iyn.imiciilly s:a'rC.e when the mi;ial pelvic CT was performed, a coivrast-enhaiiced CT of the pelvis show? I'ighi pelvic
fri;c lures and ac iive contrast extravasation ii<n-nu) with mass effect ■:■:: the bladder. This hncn'.g p:c:v.p:ed angiographic stuck
of ihe internal time arteries, b Selective angiogram ot" me r;ehi intern.; I iliac shows no contriisl exiravasiili on. As :he patient
was hemodynamically stable, no embolization was performed.
5.4
Endovascular Therapy
Once abdominal hemorrhage has been ruled out
by FAST, CT, or DPL with continued hemodynamic
instability or if contrast extravasation is demon-
strated on CT the patient should be transferred to
the angiographysuite.lt is imperative that the resus-
citative process is not impeded by this transfer, and
that a full complement of clinical staff accompany
the patient during angiography and embolization.
It is important that angiographic evaluation is not
delayed, since patients who have experienced signif-
icant blood are at risk ot becoming coagulopathy.
It is vital, therefore, to have a variety of blood prod-
ucts available, and coagulation/hematologic studies
should be performed before, during, and after the
resuscitation phase.
5.4.1
Access to Vessels
A femoral approach is preferred. If the side of the
pelvic injury is known, the contralateral femoral
artery should be used. This is because it is easier to
catheterize 2nd- and 3rd-order vessels on the con-
tralateral side, over the aortic bifurcation. If bilat-
eral femoral artery access is impaired, an axillary or
brachial approach can be used. An upper extremity
approach is sometimes useful if an external pelvic
fixator has already been placed or there are bilat-
eral pelvic injuries. Ultrasound guidance may be
helpful in patients with large hematomas involving
the groin.
5.4.2
The Initial Pelvic Arteriogram and Further
Studies
The angiographic search for bleeding should start
with a pelvic arteriogram with a 5 F pigtail cath-
eter positioned above the aortic bifurcation. The
most commonly injured vessels include the supe-
rior gluteal, internal pudendal, obturator, infe-
rior gluteal, lateral sacral, and iliolumbar arteries.
The arteries that are injured tend to be associated
with the bony injury; thus sacral fractures and
sacroiliac joint disruption are associated with
superior gluteal, iliolumbar, and lateral sacral
arterial injury. Fractures of the pubic ramus and
acetabulum tend to cause injury to the internal
pudendal and obturator arteries. Therefore, one
should pay attention to the plain films or CT to
direct the angiographic evaluation. If no bleed-
ing is observed, selective right and left internal
iliac arteriograms should be performed. Oblique
views frequently help "open up" the branches of
the
:. Wong ;ind A.G.Roberts
Access to either the contralateral or ipsilateral
internal iliac arteries can be facilitated using a Walt-
man's loop technique with a Cobra 2 catheter; alter-
natively, a long reverse curve catheter can be used.
Care must be taken not to catheterize too distally so
as to ensure visualization of the lateral sacral and
iliolumbar arteries [50]. Carbon dioxide offers an
alternative contrast agent that has the benefits of no
allergic reactions, nephrotoxicity, or volume limi-
tations, low cost and flexibility of use with differ-
ent sized catheters [51-53]. High-pressure contrast
injections should be avoided since they may poten-
tially dislodge newly formed clots and result in loss
of hemostasis [54].
Angiographic Appearance of Hemorrhage
See Table 5.3 for the angiographic manifestations of
vessel injury [54]. Care must be taken not to confuse
the normal uterine blush or bulbospongiosal stain
'.villi the blush associated, with contrast extravasa-
tion (Fig. 5.2). Reported causes of false negative arte-
riograms include intermittent vasospasm, spontane-
ous vaso-occlusion of a bleeding artery by thrombus
formation, venous bleeding that is not shown by
arteriography, and technical difficulties selectively
catheterizing the bleeding artery [54]. Arteriove-
nous fistulas and pseudoaneurysm are recognized
late complications of pelvic trauma.
5.4.4
Embolization Agents
Embolization of visualized bleeding site(s) in the
pelvis is typically performed using Gelfoam. Gel-
foam pledgets have excellent properties for trauma
use because they usually dissolve over several weeks
and may allow for re canalization of the vessel fol-
lowing healing. The size of the particles is also opti-
mal because they are large enough not to invade the
capillary bed, while small enough to prevent flow
from collateral vessels and stop bleeding. Gelfoam
powder, which has a much smaller diameter, should
not be used for pelvic bleeding since it has the poten-
tial to cause ischemia and has been implicated in
nerve damage [55].
"Scatter" embolization using a Gelfoam 'slurry'
provides a rapid solution in the face of multiple
bleeding points and a hemodynamically unstable
patient who cannot tolerate the time required for
subselective catheterization. In this scenario, the
catheter is placed proximally in the internal iliac
trunk to allow flow of the embolic material to all
bleeding points. If the patient is hemodynamically
stable, further subselection can take place in search
for the bleeder. However, it must be stressed that an
ideal subselective embolization must take second
place to the cardiovascular status of the patient.
To protect the gluteal arteries from inadvertent
embolization, spring coils can be placed at their ori-
gins. Coils can also be added for larger lacerations in
higher-caliber proximal vessels. In this scenario, Gel-
foam may flow straight out of the vessel and into the
pelvic cavity, but a large-caliber, proximally placed
coil would not. Gelfoam may then be placed on top
of the coil, which acts as a scaffolding, and if neces-
sary, a second coil may be placed creating a "Gelfoam
sandwich". Ideally, the injured segment should be
crossed so a distal coil can be placed which will have
the beneficial effect of preventing retrograde flow
from collateral vessels beyond the injury. Coils can
be used to treat AVFs and pseudoaneurysms, closely
packed tip to and proximal to any observed lesion.
Absolute alcohol and particulate polyvinyl alco-
hol (PVA) emboli have no role in the trauma patient.
Table 5.3. The angicgrapiiic m.iiihestaUC'ns of vessel injury [54]
Angiographic manifestations of vessel injury
Arterial cut-off
Muni! irregularities or flap
Laceration
Thrombosis
I ii&ed ion
Free-flow contrast extravasation
Stagnant intra parenchymal a or u:r. illation of contras
Parenchyma I blush
Stagnant arterial or venous flow
I'MTuse v,i ;; i.-s c o n s l r i c : i i:-- :i
Pseudoaneurysm
Arteriovenous fistula
Vessel displacement
Angiographic nunifesiat.
Free-flow contrast ei
Stagnant intraparenchymal ;u
Disruption of visceral contou
Displaced organ
intro parenchymal avascular z
Embolization and Pelvic Trauma
Fig 5.2a-d.Thirly-c>iie-yeai-o!d male involved m a motorcycle accidenl collision and s litre red multiple ink' lies inch, ding • ighi
reran r tYaciure and .1 laceration 0; -he rigid bullock. The patient was iiypotensive and !■■:■ cletinne pelvic fractures were seen
on plain iilm. a f-vivic CT demon si rated active extravasation 01' contrast from a rigid superior gluteal artery branch and an
expanding rig 111 sice, b Ai :e: ial plus; angiogram ■ ■:' I lie 1 igb: inter 11 a I iliac demons: rates i.\\- ■ aivas of e.v.i avasation. c Venous
pliase angi' 'gum snows retention 0:' conlias: in die s impeded area:;. (1 K:st-Gelloam embolization angiogram shows 1:
of the distal branches oi" the superior gluteal artery.
Unlike Gelfoam, which sprires the capillary bed ves-
sels, alcohol causes sclerosis of all vessels it comes
into contact with, including those at the capillary
level. This results in irreversible end-organ ischemia
Angiography may reveal injuries to larger more
proximal vessels, such as the common iliac or exter-
nal iliac arteries, traditionally treated surgically.
However, with the advent of covered stents, inter-
ventional radiologists may be able to offer a less
invasive endovascular solution [42, 56]. In some
unusual circumstances, temporary occlusion bal-
loons can be used to obtain hemostasis allowing for
surgical repair.
Following embolization of a bleeding site, the
internal iliac artery should be checked proximally to
make sure there are no other bleeding sites that were
not recognized earlier. Because of the rich cross-
'.. Wo jig and A. G. Roberts
pelvic collateral supply, the contralateral internal 5.6
iliac artery should then be evaluated and embolized Conclusion
as necessary. Once embolization is felt lo be com-
plete, it may be reasonable to perform a final flush
pelvic arteriogram.
5.4.5
What To Do If No Bleeding I s Seen?
The "Check" Arteriogram
Inthe setting of hemodynamic instability and unde-
tectable extravasation from the pelvis on angiogra-
phy, further investigation of other vessels includ-
ing the lumbar branches, branches of the common
femoral artery, superficial femoral artery, and pro-
funda femoral artery should be performed. If there
is potential for splenic, hepatic, or renal injury, these
vessels should also be evaluated. If all other poten-
tial arterial sources have been excluded and the
patient remains hemodynamically unstable, then
empiric embolization of the internal iliac arteries
may be performed.
Complications
Endovascular therapy is now established as the
treatment modality of choice for retroperitoneal
and pelvic bleeding secondary to trauma. Despite
evidence to support earlier involvement of the inter-
ventional radiologist, some trauma centers still fail
to consider angiographic study until much later into
the resuscitative process. The adoption of an evi-
dence-based trauma algorithm (Table 5.2) is vital to
ensure rapid and decisive treatment.
Cookbook:
For selective angiogram
• 5 French Sheath
• Gtidewire (Terumo)
■ Long reverse curve catheter (RUC
excellent catheter for trauma as it i
- Cook, Inc) an
s for fibroid emboli-
Alternative catheters
• C2 catheter, can beused to as is, oi
Waltraan Loop
used to form a
Although a post-embolizat ion arteriogram may show
complete hemostatic control, a second embolization
maybe needed. Vessels that had previously "clamped
down'Vvasoconstricted due to shock may re-open fol-
lowing reperfusion from the ensuing resuscitation
and increased systemic blood pressure [54]. These
vessels may have initially been injured, but were not
detectable on initial arteriogram and therefore pro-
vide a new source of hemorrhage.
Embolization, by definition, reduces blood flow
distally. Therefore, it is no surprise that distal necro-
sis is a recognized complication of trauma emboli-
zation. However, unintentional reflux of emboliza-
tion material from the internal iliac into the femoral
artery can cause inadvertent ischemia in the leg.
Sciatic palsy with associated foot drop and sacral
plexus palsy has been reported [57]. Embolization
of the superior gluteal artery in a patient who will be
subjected to prolonged bedrest may cause sacral and
buttock ischemia leading to skin break down [58].
Sexual dysfunction seems not to be a complication
of bilateral internal iliac artery embolization, but is
more likely a result of nerve injury secondary to the
fracture or pelvic trauma [59].
Embolization materials
• Gelfoam - may be cons titu ted .'.:; pledgels. torpedoes,
or slurry. Do net use Gel foam powder
• Coils - may be : .:sed pari:c : .:larly to;- larger vessels
• May use in comb: nation wit:: G e I fo a :r. for "Gel foam
sandwich"
• Very occasionally i"o: large vessel trauma, occlusion
balloons or covered stents may be appropriate
> Never forge: that r lei? selective embolization and a
live patient :s preferable to a lechmc.'.l tour de force
and a dead patient!
> Long reverse curve ca:lie:er allows for :'. very fast way
to access the interna! iliacs and to perform subselect:ve
embolization cu:ck!y with .arge pieces of Gelfoam or
large coils
> Make sure if embolization done on one side, that the
other iliac artery is evali.ir.ted to make sure no collat-
eral flow
> If :liac arteries are ok, but pat:eiil stil: ::emodynami-
lm I iy unstable, check for bmbar bleeding or for bleed-
ing from branches of femoral arteries
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6 Postcatheterization Femoral Artery Injuries
Geert Maleux, Sam Heye, and Maria Thijs
Introduction 69
Incidence of Postcatheterization Vascular
Injuries 59
Pseudoaneurysm 69
■Clinical Features 69
Radiological Diagnosis 70
Treatment 70
Surgery 70
Lllrc lhslti.1 nd -Guided ■'.■■ impression Repair 70
■ Traiisciuhetet Endovascukir Techniques 71
- Uittasouiid-g'.uced Thrombin Injection 71
Arteriovenous Fistula 74
Prevalence and Natural History 74
lagnos:
75
Treatment 75
Thromboembolic Lesions
References 76
Incidence of Postcatheterization
Vascular Injuries
Among these iatrogenic femoral arterial injuries,
the formation of a pseudoaneurysm is the most
common entity. The reported incidence of iatro-
genic pseudoaneurysms ranges from 2% to 8% after
coronary angioplasty and stent placement and from
0.2% to 0.5% after diagnostic angiography [1]. These
clear differences in complication rates are basically
due to the use of larger sheaths and catheters and
due to the aggressive postprocedure! anticoagula-
tion therapy routinely used in interventional car-
diological units [2]. Arteriovenous fistulas are less
common and occur in about 1% of all percutaneous
coronary procedures. Uncontrollable groin hemor-
rhage, in situ arterial thrombosis, and peripheral
embolization are rare entities; their incidence is less
than 1%.
Introduction
The number of percutaneous femoral arterial cath-
eterizations has increased exponentially in recent
years with several million procedures performed
worldwide annually. A direct consequence of that
explosion in number of percutaneous diagnostic
and interventional catheterizations is the increasing
number of vascular complications due to the per-
cutaneous creation of that vascular access mainly
using the femoral artery. Potential complications are
pseudoaneurysm, arteriovenous fistula, uncontrol-
lable groin and/or retroperitoneal bleeding, in situ
arterial thrombosis, and peripheral embolization.
In order to deal with these complications, there is an
increasing need for quick and optimal diagnosis and
for efficient and, by preference, minimally it
treatment.
G. Maleux, MD; S. Heve; MD; M. Thijs; MD
I'epjrtiiien: <■■:' Radiology. "Jniversiiy !-!ospil,il:
Herestraat 49, 3000 Leuven, Belgium
Pseudoaneurysm
6.3.1
Clinical Features
Among iatrogenic femoral arterial injuries, the for-
mation of a pseudoaneurysm is the most common
entity. Clinicalsymptomsare pa in a nd swelling at the
site of a recent arterial puncture, and physical exam-
ination can reveal a palpable mass in case of a large
pseudoaneurysm. In a study by Toursarkissian
et al., monitoring patients with a pseudoaneurysm
of less than 3 cm in diameter, spontaneous closure
was noted in 86% of cases with a mean of 23 days
[3]. Adversely Kent et al. found spontaneous clo-
sure unusual in pseudoaneurysms larger than 1.8
cm in diameter [4]. These contradictory findings
can probably be explained by the anticoagulation
status of the patient: spontaneous thrombosis of a
pseudoaneurysm is probably unlikely in an antico-
agulated patient. As the vast majority of patients
presenting with a postcatheterization pseudoaneu-
rysm in our institution is anticoagulated, we rou-
tinely treat every pseudoaneurysm with a diameter
of more than 1 cm.
6.3.2
Radiological Diagnosis
Duplex ultrasound is a simple, cheap, and effective
tool to correctly diagnose a pseudoaneurysm. Real-
time ultrasound imaging shows an echo-poor soft
tissue mass anterior to the femoral artery and distal
to the puncture site. The surrounding fatty tissues
canbeechogenic due to the hemorrhagic infiltration.
Doppler evaluation shows the classic triad of swirl-
ing color flow in a mass separate from the underly-
ing artery, color flow signal in a track leading from
the artery to the mass (pseudoaneurysmal neck),
and a to-and-tro Peppier 1 waveform in the pseudoa-
neurysmal neck [5] (Fig. 6.1). Additionally, duplex
ultrasound is also the imaging tool of preference to
guide treatment like compression repair or throm-
bin injection, and it can also be used to perform
follow-up studies after treatment. Of course, MR and
CT imaging are also valuable tools, but these tech-
niques are expensive and need additional contrast
medium administration. Catheter angiography can
also diagnose a pseudoaneurysm, but because of the
invasiveness of the procedure, this technique is no
longer considered a valuable option.
Fig.6.1. Color Doppler ■.dtrasouid o: the groin shows a pseu-
doaneurysm (iPsfiTfsfc) with Li diameter of 1 cm and color flow
centrally in the pseud o.areuiysmjl carky. ; :uplex scanning of
the pseudoaneurysnul nee It demonstrates a typical to- and -
fro signal
6.3.3
Treatment
6.3.3.1
Surgery
Surgery has been the classical treatment of iatro-
genic groin pseudoaneurysms for many years but
since the publication of new, less invasive tech-
niques, the number of surgical corrections has
diminished significantly in most institutions.
Briefly, the surgical technique consists of opening
the groin, dissection of the pseudoaneurysm and
injured vessel above and below the puncture point,
evacuating the surroundim; hematoma, ami sutur-
ing the bleeding point with or without placement
of any absorbable synthetic graft material over the
bleeding point. Despite the significant decrease in
number of surgically repaired pseudoaneurysms,
there are still some strict indications for surgery
(and these surgical indications are contraindica-
tions for percutaneous repair}:
a)rapidly expanding pseudoaneurysm due to con-
tinuous bleeding,
b)infected pseudoaneurysm,
c) symptoms of compression of the pseudoaneurysm
on surrounding tissues like the femoral artery
(distal ischemia), femoral nerve (neuropathy),
overlying skin (skin lesions),
d) pseudoaneurysm not responding to percutane-
ous treatment.
The results ot surgical repair are nearly 100%, but
this treatment is not free of morbid ity or even mortal-
ity, in most cases due to the significant cardiac comor-
bidity of the affected patients. In a cohort study of
55 patients presenting with arterial injuries produced
by percutaneous femoral procedures, Franco et al.
reported nine postoperative wound complications,
five myocardial infarctions, and two deaths [6]. These
numbers result in a postoperative morbidity rate of
25% and a postoperative mortality of 3.5%.
6.3.3.2
Ultrasound-Guided Compressio
technique, first described by Fellmeth et al.,
placing an ultrasound probe directly
over the neck of the pseudoaneurysm followed by
downward pressure of the probe, which will result
in occlusion of the neck of the pseudoaneurysm [7].
Duplex examination will dei
Postcitbctenzaiion Femoral Artery Injui
flow into the pseudoaneurysmal lumen. The pres-
sure must be continued for at least 10 mimites and
then controlled by duplex ultrasound. If there is still
a residual flow into the pseudoaneurysm, continued
pressure for 20 minutes is mandatory. This tech-
nique, which was very popular in the last decade,
has some important drawbacks. It is a time-con-
suming and painful technique, mostly requiring
oral or intravenous analgesics to avoid excessive
patient discomfort. Additionally, the procedure
can be contra indicated, not only when one of the
above-mentioned indications for surgery is present,
but also when there is an anatomy unsuitable for
compression repair: when the neck, which must be
compressed, is located above or near the inguinal
ligament, no underlying tough structure is present
that would enable occlusion of the neck when ante-
rior compression is performed. Other disadvantages
of ultrasound-guided compression repair are the
limited success rate in anticoagulated patients and
in patients presenting with large pseudoaneurysms
6.3.3.3
Trans catheter Endovascular Techniques
Several transcatheterendovasculartechniques have
been described to treat iatrogenic groin pseudoan-
eurysms, all of them in the form of case reports and
some small series. Basically, two main techniques
should be mentioned, but they have only histori-
cal value: coil embolization and placement of a
stent-graft [10-12] across the pseudoaneurysmal
is that these techniques have
;ck. The i
been omitted are the cost of the de
sion of later femoral artery puncture in the pres-
ence of an overlying stent-graft, potential metallic
s tent-fractures, and the disappointing long-term
results of primary and secondary patency rates of
femoral artery stent-grafts [13,14]. The long-term
outcome of subcutaneously placed vascular coils
6.3.3.4
Ultrasound -guided Thrc
6.3.3.4.1
Cope and Zeit first described the potential interest
of thrombin as an effective embolic agent in 1986
[15]. They reported the successful direct needle-
injection of thrombin to thrombose peripheral pseu-
doaneurysms such as common iliac, peroneal, and
hepatic pseudoaneurysms. Despite this interesting
report, it was not until a decade later that the first
report of ultrasound-guided direct thrombin- injec-
tion to close iatrogenic groin pseudoaneurysms was
published, by Liau et al. [16].
6.3.3.4.2
Biochemical Working Mechanism
Thrombin is an active enzyme in the blood-clotting
cascade. It is formed from prothrombin (factor II
clotting cascade) and it converts inactive fibrinogen
into fibrin, which actively participates in the for-
mation of thrombus. When injecting thrombin into
the pseudoaneurysmal lumen, thrombus formation
will be clearly accelerated as the blood flow in the
pseudoaneurysm is turbulent or even nearly static.
These phenomena will lead to a high concentration
of thrombin in the pseudoaneurysm over a period
of time, long enough to activate the clotting cascade
into a definitive direction of clot formation. This
activation of the clotting cascade due to the injection
of thrombin will not be restrained or stopped when
the patient is antuoayiilaied by heparin or warfarin-
derivatives or when the patient is anti-aggregated.
However, Kruger etal. demonstrated the increase of
thrombin-antithrombinlll complexes in the periph-
eral circulation 2, 5, and 10 minutes after thrombin
injection in the pseudoaneurysm, indicating that
some amount of thrombin passed into the circula-
tion [17]. No transcatheter occlusion of the neck of
the pseudoaneurysm was performed during injec-
tion. Possible pathways of this passage are a direct
flow of thrombin from the lumen of the pseudoa-
neurysm into the feeding artery and here binding
to antithrombin III; another possible mechanism is
the formation of thrombin-antithrombin III com-
plexes in the pseudoaneurysm and then passage of
the whole complex into the feeding artery. A third
pathway is that thrombin is partially absorbed from
the surface of the pseudoaneurysmal cavity into the
venous drainage. This increase in thrombin-anti-
thrombinlll complexes does not lead to a higher risk
of peripheral clot formation, neither in the arterial
nor in the venous system. Today, thrombin is avail-
able in the form of human thrombin and as bovine
thrombin. Due to production costs, human throm-
bin is more expensive than bovine, but the latter is a
non-human substance which potentially may induce
allergic or even anaphylactic reactions [18].
6.3.3.4.3
Technique of Percutaneous Embolization
Thrombin injection can be performed in an inter-
ventional suite or even in an ultrasound room, but
precautions must be taken in order to avoid poten-
tial infection during the procedure. Therefore the
patient's affected groin must be cleaned and disin-
fected with povidone-iodine and covered with a ster-
ile drape. Before starting the procedure the distal
pulses of the affected limb are examined. A steril-
ized 7.5- or a curved 3.5-MHz array transducer is
used to guide the whole procedure. A 3.5-MHz array
probe can be helpful when treating an obese patient
or when the pseudoaneurysm is surrounded by mas-
sive hematoma or by massively infiltrated subcuta-
neous fatty tissues. Although most interventional
radiologists inject some local anesthetics before
introducing the puncture needle, the embolization
procedure can also be done without any anesthetics
and without any discomfort for the patient [19]. A
21-gauge puncture needle is clearly large enough to
inject the thrombin, avoiding the use of larger (20-
or 19-gauge) needles. Under ultrasound guidance
using a freehand technique, the puncture needle
(e.g., spinal needle) is placed in the middle of the
pseudoaneurysmal lumen (Fig. 6.2a,b). Injection of
thrombin is done safely when the ultrasound probe
is directed longitudinally to the femoral arteries for
having a correct view on the pseudoaneurysmal neck
and lumen (Table 6.1}. After switching the gray-scale
imaging to color Doppler imaging, thrombin can
be injected very slowly and under continuous color
Doppler control. After each injection of 0.10 ml of
thrombin, the residual flow in the pseudoaneurysm
is evaluated and when no more Doppler signal can
be depicted, the injection is stopped (Fig. 6.2c). In
the case of a multilocular (or complex) pseudoan-
eurysm, repositioning of the needle into another,
Table 6.1. My lookbook i material : for ultra sound -guided
thrombin injection
- 7.5 or 3.5 MHz array ultrasound probe
- Povidone-iodine
- 21-gauge spin.:! neer.le (Tej n m .:■ iiiiiope. i.iruveii, Refill in)
- Human thrombin ( Tissual '. -uo, Baxter H viand I in inline-,
Vienna, Austria)
Fig.6.2a-c. a Color Doppler ultrasound shows color flow cen-
trally in the pseudouiieurysniai cavity i,j. <;ci isk), which has a
diameter of 1.7 cm. b Under grav-scale iLirasound the spinal
needle {iiiroi; ) is positioned in the middle of the pse-;doun-
eurysmal cavity, c Color Popper ukrasound after thrombin
embolization shows uosence of color signal in the thrombosed
pseudoaneurysm l -.utcrisk i. 7 lie Ivn'.oral a: ;eries remain nor-
mally patent
Postc.atlietenzadon Femoral Artery Injui
Fig.6.3a-c. a Colo:' Poppler dtiasoand clemonstraies color
riow in 7 fir nios: o;o\:mjl i [.:■ the fejnor.i I artery! pse.alo;"
rysiii.il cavity i,isrri:.N"A) ,10c par:ial opacification of the distal
m 1 )- b After piaiclmiiig die most proximal cavity
iijg it spinal needle Unom, c ti'.rombni injection resulted
complete occlusion of boili proximal iriirr-.'/.d) and distal
still reperfused lobe can be necessary to completely
close the pseudoaneurysm, but we advise starting
the embolization procedure by puncturing the most
proximal (to the femoral artery) cavity. In the major-
ity ''I case 1 ; embolization ol 1 lie niO'Sl proximal cavity
will lead to concomitant occlusion of the distal cavi-
ties, as these are in direct connection with the proxi-
mal one (Fig. 6.3a-c). Some residual flow signals in
the neck of the pseudoaneurysm, but without any
signal in the lumen, can be considered a successful
embolization. After the procedure, physical exami-
nation of the distal pulses is indicated to exclude
distal embolization.
Variants of the above-described technique are
also mentioned in the literature, but they are more
complexand more expensive and no longer promoted
today. A technique of ultrasound-guided thrombin
injection after transcatheter balloon occlusion of
the neck of the pseudoaneurysm was promoted in
the United Kingdom a lew years ago [20, 21] but this
technique needs additional, contralateral puncture,
contrast medium administration, and manipula-
tion under X-ray guidance. Transcatheter injection
of thrombin ii
is another comple?
ity of the pseudoaneurysm
;dure with the same draw-
the balloon occlusion technique. Another
variant technique is the ultrasound-guided injec-
tion of saline beneath the neck of the pseudoaneu-
rysm [22]. This particular technique, described by
GEHLiNGetal., should result in rapid occlusion of the
neck and subsequently will thrombose thepseudoa-
neurysmal cavity [22], Unfortunately no large series
or confirmations from other centers are reported.
6.3.3.4.4
Results
Immediate success defined as complete thrombosis
ot the pseiidoaneiirysmal cavity following throm-
bin injection is very high, and most series report
an immediate success rate in between 90 and 100%
(Table 6.2). Failure of percutaneous embolization
can occur in multiloculated pseud oaneurysms,
when one or more lobes are not punctured; Sheim an
ars of failure [23]. They
et al. sought the
concluded that the volume of the p
Table 6.2. Overview of results of published series on percuta-
neous thrombin injection to tre.it iatrogenic, postci'.ti'.eteiiz.i-
tion pseuclo aneurysms
Author
Nci-i^er of
p..1i:cl";iS
Technica
1 Compli-
KANGetal. [35]
21
95%
_
Paulson et al. [8]
114
96%
4
Taylor et al. [36]
29
93%
-
Pezzullo et al. [37]
23
95%
1
LaPerna et al. [38]
70
94%
1
Gale et al. [39]
20
100%
-
Bhophy ei aL [40]
15
100%
-
MALECxetal. [19]
100
98%
-
Khoury et al. [25]
131
96%
3/131
Friedman et al. [41]
40
97.5%
1
Owen et al. [20]
25
100%
1
Matson el al. [21]
28
85%
1
the neck diameter, and the thrombin dose were not
predictive criteria. They only found that failure of
treatment may indicate an occult vascular injury
and that surgical repair rather than reinjection
of thrombin should be considered. Percutaneous
thrombin- injection, even without additional trans-
catheter occlusion of the pseudoaneurysmal neck, is
also very safe; the reported complication rates vary
between 0% and 5% (Table 6.2). Complications are
rare and can occur immediately or long after the
embolization procedure [24]. Distal embolization is
reported and can be due to passage of clot into the
arterial circulation, but most probably will occur
due to needle misplacement in the femoral artery
and subsequently direct thrombin injection into
the femoral artery [25]. Another rare complication
is allergic or even anaphylactic reaction, but only
when bovine thrombin is used [18]. Mid- and long-
term results of percutaneous thrombin injection are
also very good. In a study by Maleux et al., 70% of
previously occluded pseudoaneurysms disappeared
completely whereas in 25% of cases a small, residual
hematoma was tound; in 3.5°b a partial reperfusion
of a previously thrombosed pseudoaneurysm was
revealed by color-duplex ultrasound after a mean
follow-up of 99 days [19] (Fig. 6.4).
The simplicity and reproducibility of the proce-
dure as well as the high efficacy and very low com-
plication rate of percutaneous thrombin injection
under ultrasound guidance have made it the treat-
ment of choice for postcatheterization pseudoaneu-
rysms in many institutions [19, 26].
Fig. 6.4. Ultrasound of the groin. : ;;': cays arte? thrombin iniec
(ion reveals a small, resid
(he femoral arteries
6.4
Arteriovenous Fistula
6.4.1
Prevalence and Natural History
Iatrogenic, posk'.ithelenzation arteriovenous fistu-
lae are by far less frequent than postcatheteriza-
tion pseudoaneurysms. Kelm et al. and Perings
et al. found an incidence of 1% in a prospective
study including more than 10,000 patients who
underwent cardiac catheterization [27,28]. This
study also revealed five significant and independent
risk factors for developing an iatrogenic arteriove-
nous fistula: procedural administration of heparin
> 12,500 IU, Coumadin therapy, puncture of the left
groin, arterial hypertension, and female gender.
Follow-up of these patients demonstrated that one-
third of all arteriovenous fistulae closed spontane-
ously within one year and the majority even within
the first four months. Additionally, the authors
found that the majority of patients who suffer from
an iatrogenic arteriovenous fistula do not develop
clinical signs of hemodynamic, significance during
follow-up, and subsequently in most ca
treatment is not needed.
Postcatheterizador! Femoral Artery Injui
6.4.2
Diagnosis
Auscultation of the groin classically reveals a (new)
continuous bruit after sheath removal, and in most
cases a concomitant hematoma and/or pseudoaneu-
rysm can be found. The clinical diagnosis must be
confirmed by duplex ultrasonography, which will
show a triad of typical signs: (1) a colorful "speck-
led" mass at the level of the puncture site, (2) an
increased venous flow with a lack of respiratory
variation and a pulsatile arterial component in the
affected vein, and (3) decreased arterial flow distal
to the suspected fistula. As for pseudoaneurysms, an
arteriovenous fistula can also be detected by more
sophisticated imagine tools like MR-,CT-and cath-
eter angiography, but the standard imaging tool is
still duplex- ultra sound.
6.4.3
Treatment
According to the study results of Kelm et al., in
the majority of patients suffering from an iatro-
genic arteriovenous fistula, no invasive treatment
is needed or even indicated [27]. In case of clinical
symptoms due to the fistula, surgical repair, covered
stents, or compression repai
options [11, 12, 29]. The last
: the therapeutic
has a rather low
rate. Covered stents seem to be an attrac-
tive and minimally invasive alternative (Fig. 6.5a,b),
although many questions about long-term patency,
stent and graft fatigue still exist. Open surgical
repair is very effective and durable, but is not free
of perioperative morbidity and mortality.
Thromboembolic Lesions
In situ thrombosis of the common femoral artery
due to catheterization or manual compression after-
wards are rare lesions but, if diagnosed late, can have
a tragic outcome. Caution must be the rule when
puncturing and certainly when compressing too
much and too long a graft (e.g., in patients with an
aortofemoral graft). When performing catheteriza-
tion in children or young adults, persistent spasms of
the femoral or brachial artery can induce an in situ
thrombosis and potentially provoke distal embo-
lization of a part of the clot. Small-sized sheaths
and catheters as well as administration of vasoactive
drugs can avoid this complication. In situ throm-
bosis of the punctured artery is also described in
Fig.li5a,b. : : e.e;l:v T LUi£ic:\a?:v of the right femoral bifu
ally from die de^y femoral artery, b After "
USA], the arteriovenous Sftuh is completely excluded
patients treated with closure devices at the end of an
endovascular procedure [30-32]. In most instances
these complications must be corrected surgically,
although interventional, endovascular management
such as transcatheter thrombolysis or wire recanali-
zation and balloon dilatation can be successful [33,
34] (Fig. 6.6a,b).
Fig.6.6a,b.A 9-year-olri girl presentee, with progressive claudi-
o.ii :■■'•!. V- 'iilaine stage _o. for iiie pas: 3 ill- 'in lis. ■? Ji e previous!!"
underwent multiple oirili.;." catheterizations from the right
groin, a Selective angiography o:' lire right femoral bifurca-
demonslrates louil occlusion of the proximal part of the
gin common femoral artery (linv-ns). b After wire recana-
zation and bullion angioplasty (Wanda bakoon 5x40 mm,
Boston Scientiiic. \a;ick, MA, USA: an acceptable patency
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137:462-464
7 Iatrogenic Lesions
Michael D. Darcy
Introduction 79
P hysi op at ho lo gy 79
Clinical Considerations 81
Anatomy 82
Technique? and Equipment S3
Access Li rid Delivery 83
Embolic Agents 85
Alternative Techniques 87
Ha'l::in !'a— panade 87
Uncovered Stents 87
■ Stent Crafting HS
Results 89
Hepatic 89
:« .-Ml 90
MisceiUntiiu* injuries 91
Complications 91
r iitti : e Developing:'.: .-rid Research
Conclusion 94
References 94
Fortunately, the interventionist often has the ability
to manage these complications, and embolization is
one of the primary techniques utilized.
Throughout the 1970s numerous case reports
appeared demonstrating the ability to successfully
embolize iatrogenic bleeding in a variety of organs
[1-4]. While these reports demonstrated the proof of
concept, these embolizations were done with large 6
to 7 Fr catheters and often the arteries were occluded
at a fairly proximal level. With the development of
smaller catheters and improved embolization mate-
rials, it is now possible to advance super- selectively
and occlude the artery right at the site of injury.
Since modern embolization techniques allow effec-
tive control of bleeding while posing less of a risk
to the target organ, embolization has become the
method of choice lor managing many forms of iat-
rogenic hemorrhage.
Introduction
Physiopathology
Since the beginning ol both su rgery and percutaneous
interventions, vascular injury lias nl'.vays been one of
the potential complications. Bleeding can complicate
a wide range of procedures from simple biopsies or
venous access cases up to more complex angioplasty,
drainage procedures, or surgeries. This can be a pri-
mary injury that occurs at the site of the pathology
that is being treated, such as arterial rupture during
percutaneous transluminal angioplasty (PTA). Alter-
natively, vascular damage can be a secondary effect
such as when a hepatic arterial branch is injured
along a percutaneous tract to the bile ducts (Fig. 7.1).
M. D. Darcy, MD
Professor of Radiology and Surgery, Division of Diagnostic
Rodiology, Chief, !nlerve:i:ii;:i.il K.idioiogv Sec-ion, Washing-
ton University School or Medicine. Mol.inc^iodt Institute of
Radiology, 510 S. Kingshighway Blvd., St. Louis, MO 63110,
USA
Iatrogenic vascular injuries that require embo-
lization are most often arterial in origin. Venous
injuries rarely cause clinicallj' significant bleeding
since local hematoma caused by bleeding from the
injury will often compress the low-pressure vein
and tamponade the bleeding. An exception to this
is when a large vein is disrupted along a drainage
catheter tract. In this setting, bleeding may wick
along the catheter or enter the catheter itself if the
catheter side-holes are inappropriately positioned
in the parenchyma. Aside from the low frequency
of major venous bleeding, venous bleeding is also
difficult to diagnose arteriographically, plus access
to the vein for embolization may be limited. For
these practical reasons, embolization techniques to
correct iatrogenic hemorrhage have focused on arte-
rial bleeding.
Iatrogenic lesions tend to be simple traumatic dis-
ruptions of the artery, so unlike true aneurysms, the
Fig. 7.1. a Right hepatic arteriogram in ,1 p l:. L l e j j t will', severe bleeding after
percutaneous biliary drainage. A pseuacane'ai ysm is seen along the tract
extravasating ;'<ir 'cir! inlo the biliary ,-a:heter. b Spot image
ihowing an angioplasty balloon being ;:sed v: ta:'.:pom;de the bleeding.
:n advanced into the pseudoaneurysm. c
ows microcoils in place and no further
bleeding
defect usually extends through all layers of the arterial
wall. The size of the defect may vary with the mecha-
nism of injury. An artery damaged by a needle pass
during biopsy may have a very focal wall defect. On
the other hand, an artery split during a PTA may have
a long linear defect. The size of the defect may alter the
ease with which embolization can control the bleed-
ing. The size of the defect can alter the presentation.
Injury to a small hepatic branch may present remote
in time from the original procedure that caused it and
may present only with annoying persistent bleeding
into the biliary drainage catheter without any signs of
hemodynamic instability. A large rupture of a main
hepatic or renal artery however wilt usually lead to
immediate pain, tachycardia, and hypotension.
The signs and presentation of an arterial injury
will also vary depending on the location of the injury
with respect to the surrounding tissue. If the damaged
artery is deep inside a solid organ like the liver, the
bleeding may be relatively contained by the surround-
ing tissue and a pseudoaneurysm may form without
signs of major hemorrhage (tachycardia, hypotension)
being present. Instead the presentation maybe more of
a chronic low-grade bleeding into a drainage tube or
adjacent structure (e.g. into a calyx causing hematuria
or into a bile duct causing hemobilia). In some cases
intrarenal or intrahepatic pseu do aneurysms may even
be found incidentally on cross-sectional imaging done
for other reasons. However, if the injured artery is only
surrounded by loose areolar tissue or fat, the bleeding
may not be constrained and considerable hemorrhage
may ensue. Aside from surrounding native tissue, one
must remember that the bleeding may be partially
tamponaded by the presence of the tube that caused
the injury in the first place. In fact some pseudoaneu-
rysms or even gross hemorrhage will not be evident on
the initial arteriogram with the drainage catheter in
place and will only become evident once the arterio-
gram is repeated after removing the drainage catheter
ov«r ag mdewire(Fi 5 .7.2).
The location of the iatrogenic injury (i.e. how cen-
tral or peripheral it is) will have a significant effect
on the choice of therapy. A central lesion may be
less amenable to embolization for several reasons.
Embolization of a main arterial trunk may threaten
the viability of the organ supplied by the injured
vessel. It also may be difficult to embolize a main
arterial trunk without risking nontarget emboliza-
tion. In these settings, alternative techniques like
stent- grafting may be more useful.
Fortunately, injuries in solid organs like kid-
neys and liver often tend to be in more peripheral
branches. These lesions are often inaccessible to the
surgeon for direct repair and so surgical therapy
involves very aggressive approaches such as main
arterial ligation or partial resection of the organ.
This provides a unique advantage for embolother-
apy since a peripheral, focal source of bleeding can
often be embolized while sacrificing only a small
portion of the organ. Thus repair by embolization
will preserve a much greater percentage of the organ
than would be possible with surgical repair.
Clinical Considerations
Some bleeding is natural after placing a catheter
through a very vascular organ such as a kidney or
liver. Therefore one of the first tasks is to decide
when to proceed to arteriography. In some cases, iat-
rogenic hemorrhage is profound with rapid onset of
tachycardia and hypotension. In this setting imme-
diate arteriography is clearly warranted. The pres-
ence of pulsatile blood flow out of the tract during
a tube exchange is another indication that angiogra-
phy is needed. The decision is less clear when there
is just low-grade continued bleeding such as bloody
output from a nephrostomy catheter that fails to
clear after a few days.
One should first insure that the patient does not
have a coagulopathy or thrombocytopenia that could
account for the continued bleed ing. Venous oozing that
might normally be inconsequential can become quite
troublesome- m coagulopathy patients'. The patient's
medication list should also be checked for anticoagu-
lant or antiplatelet medications that may have acci-
dentally not been stopped before the procedure. The
other reason to carefully assess the coagulation status
is that embolization has been shown to be less effec-
tive in coagulopathy patients [5, 6]. This is because
coils and other embolic agents do not by themselves
provide complete occlusion to flow but rather pro-
vide a substrate for the formal ion ot thrombus which
occludes the vessel. If coagulation tests are normal or
corrected and bleeding persists a week or more or if
continued bleeding causes a significant drop in the
hematocrit, then angiography may be indicated.
The hemodynamic status of the patient should be
carefully assessed. If the patient is clearly actively
bleeding, one should proceed to angiography as
soon as possible even if the patient is hypotensive.
Fig. 7.2. n Kit: h; h^^iiit :.: ;e: iograni .-tie: fc:aiUi:'.eous b:jLi:y orajiiagc- shows sr\is:r. whejv the biliary catheter c:
nirery (iinviri, but no b^eding o: p^v.idosincm vs:::. b After rei'.icvaig the biliary o.ulielc] over ■,-, guidtwue. re-pear nr
shows extravasation or conlrasr alo:ig the tract (arrow)
Waiting for the patient to stabilize may waste pre-
cious time, and in fact it may not be possible to
stabilize the patient until the bleeding is stopped.
Although a few steps are necessary to try to stabilize
the patient, resuscitation efforts should be carried
on concurrently with the angiographic efforts to
stop the bleeding. The patient should have several
large-bore venous lines for fluid resuscitation and
blood transfusion. Blood should be typed, crossed,
and readily available. Drugs and equipment needed
to start a vasopressor infusion should be at hand.
Even if the patient does not appear to be actively
bleeding at the start of the arteriogram, one must
assume that they may develop significant blood
loss during the case. Wire manipulation or pres-
sure injections in the injured artery may stimulate
increased bleeding. Also if biliary or nephrostomy
catheter removal is necessary to demonstrate the
pseud oaneurysm, massive bleeding may suddenly
occur upon removal of the catheter. Therefore some
of the same precautionary steps (large IVs, type
and cross, etc.) should be taken with the patients
with more chronic low-grade bleeding. One should
remember to check the baseline hematocrit, since a
patient who has been chronically bleeding may be
starting out with a low hematocrit and may not tol-
erate even a modest amount of bleeding.
If the bleeding is secondary to an i mi welling cathe-
ter such as a nephrostomy' or 1 bi I iary drain, one should
determine whether the catheter is still necessary. If
so, one may need to place a new catheter via a differ-
ent access. At a minimum, you should be prepared
to temporarily remove the catheter over a guidewire
during the diagnostic arteriogram. The catheter may
tamponade the bleeding, and extravasation may only
be seen with the catheter removed. In a series of 13
patients with severe hem.hlia alter biliary drainage,
live(3S°b] ofthe vascular injuries could only be identi-
fied after removing the catheter over a wire [7]. Main-
taining guidewire access is crucial to allow replace-
ment of the catheter or a PTA balloon to tamponade
the bleeding once the diagnosis has been made.
Depending on the organ being embolized and
the level of embolization, some tissue ischemia or
even necrosis may occur. Prophylactic antibiotics
maybe indicated to prevent bacterial seeding of the
infarcted tissue from developing into an abscess.
This maybe more of a concern when the embolized
artery is in an infected organ such as a renal pseu-
doaneurysm that occurs after a nephrostomy done
for pyonephrosis. Certainly if the patient has known
bacteremia, antibiotic coverage should be started
prior to the embolization.
Anatomy
Since vessels can be injured anywhere in the body, it
is not possible to discuss the specific anatomy of all
arterial beds. But there are some general anatomic
assessments common to all regions and questions
that must be answered prior to treating an iatrogenic
vascular injury.
The first important question is whether or not
the injured vessel can be sacrificed. The answer to
this partially depends on whether you would expect
the tissue d istal to the target artery to remain viable
or become ischemic after embolization. If sufficient
collaterals are available, the tissue supplied by the
target vessel may not be affected. So for example,
embolizing a gastric branch to stop post-gastros-
tomy bleeding (Fig. 7.3) is unlikely to cause any
ischemia due to the rich collateral supply around the
stomach. Tissue distal to the injured vessel may also
be safe from ischemia if there is an alternate blood
supply. For example, portal venous flow into the
liver allows safe embolization of even major trunks
of the hepatic artery.
If good collateral perfusion is unlikely, one then
must consider whether one can afford to let the
tissue become ischemic. As an example, it would
be very reasonable to embolize a peripheral renal
artery branch that was injured during a biopsy
and sacrifice a small section of renal parenchyma,
since it would have negligible effect on renal func-
tion. However if the main renal artery was ruptured
during PTA, you would not want to embolize this
artery except in dire situations since it would sacri-
fice the entire kidney.
Thorough understanding of the anatomy, in par-
ticular potential collateral pathways, is also critical
whenplanning at what level to embolize the artery in
order to insure an adequate therapeutic result. If the
target vessel is an end-artery (such as a renal arte-
rial branch) it probably suffices to deposit emboli
proximal to the injured arterial segment. However,
if there are well known collateral pathways beyond
the target artery, then it is necessary to advance
the catheter beyond the point of extravasation and
occlude the artery both distal and proximal to the
injury. Otherwise collateral flow could lead to per-
sistent bleeding.
Knowledge of collateral pathways is also critical
to allow the interventionist to check the appropriate
vessels after what appears to be a successful embo-
lization. Thus, after a gastroduodenal emboliza-
tion for post-biopsy pancreatic head bleeding, it is
Fig. 7.3. a Selective gasuc-duodenal ;u i^: iogram in a oatient with, tippe: gasty 'imrslii'a! bleeding aftei placement of a sii
lumen gastrojejunostomy (which has backed up into the stomach), b Magnified view belter showing the bleeding [arr
coming from the g,t si :cie; tin ostomy access si:e in the mid -body of the stomach, c ! :, ost embolization study arteriogram shot
microcoil in the branch that was bleeding and no further extiavasado:'.. d Left gastric arte: iogram =■ li ■ 'Wing good perfusio:
the mid -bod v th-is preventing gas:t ic ischemia
important to do both a celiac arteriogram to look for
pancreatic collaterals from the splenic artery and a
superior mesenteric arteriogram to look for inferior
pancreatico-duodenal collaterals.
Techniques and Equipment
Again given that iatrogenic injur i
anywhere in the body, a complete dis
specific techniques and equipment for all areas is
not possible, but there are some general principles
{Table 7.1).
7.5.1
Access and Delivery
An arterial access sheath is crucial to i
access in case the embolization catheter bet
occluded. The sheath will also facilitate catheter
exchanges. Typically a standard short sheath will
work. A longer curved sheath like the Balkan sheath
(Cook Inc.; Bloomington, IN) or a guiding catheter
may be useful to engage the main arterial trunk,
especially if additional support will be needed to
ease passage of the embolization catheter across a
severely angled or tortuous artery. A guiding cath-
eter may also be useful for embolizations done
from an axillary approach so that multiple catheter
\i.D. rurcy
Table 7.1. Cookbook: Sample - 1 11L ■■ ■ I . a;"^ t ; .:; n equipment list
Embolization of large accessible artery
5-Fr Cobra catheter
0.035-11]. Rentsoii o: C-lidewiie to i]e.p eng.sge artery
'Siaiiturco coils (size to maic;. resse.l 01' 'Selfcam olec.gei-;
LLT wire to push coils
Alternative cc-.tlieleis ."epenJing on vessel shape
- 5-Fr Sos of Si in in on caiheie: to engage artery
- Rosen gindewire .:i" siirf-sha:; giidem:e for exchange
- MPA or Cobf.i catheter to advance :v.oie pe:ip:.efallv
2. Embolization of small peripheral artery
■ 5-Fr Cobra. Sos, o: Simmons c.flielef to engage
arterial trunk
• MassTransit of Kenegade micro catbe:er to advance
peripherally
• Transend guidevci:.: to guide- micro catheter
■ 0.018-in.microcoils or PVA
• 0.025-in. glidewire to push microcoils through
microcatheter
3. Direct puncture for visceral a
urysni
cl-g Micro-puncture needles
0.018-in microcoils or thrombin (1,000-2,000 units)
Alternatives
- 22-gChiba needle and I [iron - , bin when smaller
access desired
- 18-g Trocai needle ic: beaer con;rol of needle and
more choices of emnojc agent to use
(can use larger 0.038-in. coils)
exchanges are not done across the origin of the ver-
tebral artery.
The size and type catheter used for embolization
must be tailored to the type of lesion to be emboli zed,
the anatomy, and how peripheral the lesion is. If the
size of the defect is huge las with wideneckpseudoan-
eurysms) or if there is potential for the embolic mate-
rial to migrate through the arterial defect (as with an
arteriovenous fistula), then larger coils or large Gel-
foam pledgets maybe needed. In that case a 5 Fr cath-
eter is necessary to deliver the larger emboli. The 5 Fr
catheter chosen will depend on the shape of the arter-
ies. A Sos Omni (A ngio dynamics; Queensbury, NY) is
a good initial catheter for selecting a variety of arterial
trunks including renal, celiac, and mesenteric trunks.
However the recurved shape may not allow the cathe-
ter to be advanced more peripherally unless a very stiff
wire is advanced out into the target artery. A Cobra-
shaped catheter is sometimes less stable when engag-
ing a main visceral trunk, but it tends to be easier to
advance more peripherally. Alternatively a recurved
catheter such as a Sos or a Simmons 2 can be used
to securely engage the trunk and then pass a stiffer
wire out into the periphery to allow an exchange for
a st raighter catheter (e.g. an MPA catheter; Cook Inc.)
that will track better peripherally. Although a hydro-
philic coated catheter may be more easily passed out
to the peripheral aspects of an artery, we do not tend
to use hydrophilic catheters because in our experience
coils tend to get stuck in hydrophilic catheters.
For more focal defects in smaller arteries, a 3 Fr
microcatheter such as the Mass Transit (Cordis;
Miami, FL) or Renegade (Boston Scientific) has sev-
eral advantages. Because they are small and very
flexible, they can be advanced very peripherally into
branches that would be too small for a larger 5 Fr
catheter. More peripheral embolization minimizes
the amount of tissue that must be sacrificed (Fig. 7.4).
Microcatheters do have several disadvantages. They
are more cumbersome to use, require a higher level
of technical skill, and only allow delivery of smaller
emboli which may not occlude the target artery as
effectively.
As an alternative to catheterization, an iatrogenic
pseud oaneurysm can be directly punctured percu-
taneously with a needle for delivery of the embolic
agent. This is most commonly done for post-angi-
ography femoral artery pseudoaneurysms, which
are discussed more fully in another chapter. How-
ever, direct puncture can also be used to access
deep abdominal lesions that cannot be reached
with an intra-arterial catheter due to tortuosity,
small vessel size, or obstruction by emboli from a
prior attempted embolization. This technique has
been applied to various hepatic and splanchnic
pseudoaneurysms using either thrombin or coils
as the embolic agents [8-12]. The puncture is done
with long 22-or 21-gauge needles when planning to
use thrombin alone as the embolic agent. Although
microcoils can be introduced through a 21-g needle,
using an 18-g needle for access gives you the option
of introducing larger 0.038-in. fibered coils. For
deep intra-abdominal pseudoaneurysms, needle
placement can be guided by ultrasound, CT, or fluo-
roscopic visualization ol injected arterial contrast.
Once the needle has been inserted, confirmation
of proper position in the pseudoaneurysm is con-
firmed by aspiration of blood and injecting contrast
directly through the needle. Thrombin or coils can
then be introduced directly through the needle into
the pseudoaneurysm.
In solid organs such as the liver, major iatro-
genic bleeding is sometimes due to communication
between the tract and a major venous structure.
Arteriography will usually not reveal any abnormal-
ity nor provide an access for therapy. In most cases of
venous bleeding, simply leaving the drainage cath-
Iatrogenic Lesions
Fig. 7.4. a Right renal arteriogram showing a pse.;doane : arysm in a patient
who developed perinephiic hemorrhage after :", biopsy h A microcaiheter
has been advanced peripherally into [he specific branch [iUiou-'i leading to
the pseud oaneurysm. c Mid-.ir:eri;i' phase of die post embolization arte-
riogram shows good o reservation of the n
eter in place or sometimes upsizing the catheter will
effectively tamponade the smaller venous bleeds. If
tamponade fails to control the bleeding because of
the large size of the vein that was transgressed, embo-
lization can be done via the tract itself (Fig. 7.5). The
drainage catheter is first replaced with a sheath with
a side arm adaptor or a Lieberman catheter (Cook
Inc.) with an attached hemostatic valve with a side-
arm adaptor (Merit Medical; South Jordan, UT). The
sheath or catheter is pulled into the tract and con-
trast is injected into the tract while acquiring digi-
tal subtracted images. Once the venous connection
is identified, coils are placed in the tract across the
point where the tract and vein intersect. After tract
embolization, it may not be possible (or desirable}
to re-advance a drainage catheter down the tract.
Therefore a new access for draining the biliary tree
should be secured before starting the tract embo-
lization. Although rarely needed in our practice,
tract embolization has been effective at stopping the
bleeding when this technique was used.
7.5.2
Embolic Agents
Coils are possibly the most commonly used devices
for embolization of iatrogenic bleeding because they
are readily visible during fluoroscopy, they can be
deposited very precisely, and they generally provide
effective occlusion. Larger coils (0.035-0.038 in.)
must be passed through 5 Fr catheters, but in our
experience these coils occlude arteries more effec-
tively than the smaller 0.025-in. coils or 0.018-in.
microcoils. Thus 0.038-in. coils are preferred when-
ever vessel size permits passage of a 5-Fr catheter.
However, even 0.038-in. coils may not effectively
occlude blood flow if the patient has a coagulopathy.
One of the main functions of a coil is to provide a
nidus for thrombus formation, if coagulopathy pre-
vents thrombus formation, then blood may continue
to flow around coils, especially if they are not tightly
packed. Correction of the coagulopathy should be a
priority but may not be possible. Alternatively Gel-
Fig. 73. a Injection of contrast along ;i bikary tract showing major
communication to hepatic veins iiii ivni. b The tract in the region
of the venous com mtiiiicj lion was eniL"' elided with coils and a na so-
biliary tube wns placed lb:' ci'ainage
foam can be injected on top of the framework of
coils; this will provide more complete obstruction
to blood flow.
Gelfoam is another commonly used agent but
unlike coils it is injected and relies on flow direc-
tion. This is useful when the catheter cannot be
advanced close enough to the bleeding site to allow
placement of a coil. It is a versatile embolic agent.
It comes in sheets and is cut into appropriate-size
pieces for each case, which allows the emboli to be
easily tailored to the situation. For large arterial
defects or bleeding from large vessels, Gelfoam can
be cut into large torpedoes. For smaller vessels it
can be cut into smaller cubes. To embolize multiple
branches at once it can also be made into a slurry by
rapidly injecting it back and forth through a three-
way stopcock. Because it is a flow-directed embolic
agent, careful fluoroscopic monitoring of injections
is critical to avoid reflux into nontarget vessels. For
this reason, Gelfoam must be suspended in contrast.
Since Gelfoam dissolves after a couple of weeks, it
has the theoretic benefit of allowing vessel recana-
lization, although in some organs (such as kidney}
the distal tissue has already infarcted long before
the vessel recanalizes.
Polyvinyl alcohol (PVA) is a semipermanent
flow-directed injectable particulate agent that can
also be useful for treating iatrogenic hemorrhage.
Its main benefit over Gelloam
the particles, making it e
> the s
1.1 Hers
eof
ise them through
a microcatheter. Because of their small size they are
mostly useful for bleeding from small arteries. With
large arterial defects or arteriovenous fistulas, the
PVA can just flow out through the defect or into the
venous circulation. For iatrogenic bleeding, larger
PVA particles (>500 microns} are typically used
since smaller particles are more likely to travel into
very peripheral arterioles and are more likely to
cause tissue ischemia.
PVA has several disadvantages. Like Gelfoam,
the particles themselves are not fluoroscopically
visible, and only the contrast they are suspended in
allows you to monitor the injection. This is an indi-
rect method of monitoring the embolization since
the number or density of particles is not always
uniform in any given injection. Care must be
taken to avoid reflux and nontarget embolization.
The particles also can occlude catheters requiring
forceful and less controlled injections to clear the
catheter, or the occlusion may even be firm enough
to require removal of the catheter. Avoiding exces-
sive particle density in the embolic mixture and
frequent flushing with saline can help prevent this
problem. PVA particles may also clump together,
leading to premature occlusion of a vessel proxi-
mal to the injury. Newer formulations of PVA engi-
neered into more spherical shapes such as Contour
SE (Boston Scientific} may reduce clumping and
catheter occlusion.
Thrombin has been used for embolization with
increased frequency, especially for management
of post-catheter ization pseudoanemysms [13,14].
Occluding pseud oaneurysms with thrombin was
first described in 1986 by Cope and Zeit [15], and
even in that initial report the technique was also
used for an intrahepatic lesion, not just femoral
lesions. Being a liquid agent it is readily delivered
through even small-caliber catheters or needles.
Usually only 1-2 ml of thrombin (1000 units/ml} is
needed to thrombose a pseudoaneurysm. It must be
injected carefully, since over- inject ion of the pseu-
doaneurysm can lead to nontarget downstream
thrombosis. Most often the effect of thrombin injec-
tion is monitored in real time using color-flow ultra-
sound. In addition to its use as the primary embolic
agent, thrombin can be used to augment the efficacy
of coils. In situations where it is difficult to control
hemorrhage due to a high rate of blood flow, it can
be useful to soak the coils in thrombin to increase
their thrombogenic potential.
The liquid tissue adhesive n-buiyl cyanona-vkite
(NBCA) has been utilized in an increasing number
of applications and was recently proposed for use in
stopping active hemorrhage. In a series of 16 patients
with arterial hemorrhage (one of which was an iat-
rogenic injury), the authors reported being able
to stop active bleeding in 75% of patients without
any complications related to the embolic agent [16].
Although this is not a tremendous success rate, 10
of the 16 patients had already previously failed prior
embolization with coils or particles.
NBCA does have some attractive properties.
Since it is mixed with ethiodized oil, the mixture
is radio-opaque, which should aid fluoroscopic
control of the embolization. By varying the ratio of
ethiodized oil and NBCA, the polymerization rate
can be adjusted, thus providing the ability to cus-
tomize how far peripherally the agent will penetrate.
Finally, although it is a liquid, it does not penetrate
out into the capillaries, and thus the risk of infarc-
tion should be low. Further investigation into the
use of this agent is warranted.
7.5.3
Alternative Techniques
niques that stop bleeding without leaving behind
emboli to occlude the lumen should be considered.
7.5.3.1
Balloon Tamponade
Balloon tamponade is the simplest technique and
involves inflating either a compliant occlusion bal-
loon (Balloon Wedge Pressure Catheter; Arrow Intl.;
Reading, PA) or an appropriately sized angioplasty
balloon across the injured segment of artery. If using
an angioplasty balloon, it is recommended that low-
pressure inflation be done to avoid further tearing of
t lie ai'teiy Some recommend using a balloon that is 1
mm smaller than the size of the balloon that caused
the rupture [17]. Balloon occlusion can be used as a
temporary measure to stop hemorrhage while plan-
ning definitive therapy, or in some instances it has
been used as the definitive treatment. The theory
behind balloon occlusion as the sole therapy is that
the balloon will prevent continued extravasation
and allow the perivascular thrombus time to orga-
nize and seal the leak.
There have been a number of reports of using
temporary balloon tamponade to repair arterial
ruptures both in the iliac and renal arteries [17-20].
With this technique, a balloon is left inflated across
a ruptured artery anywhere from a few minutes
up to an hour. Repeat arteriography is done after
the balloon is deflated and if the leak persists the
balloon is reinflated. With shorter inflation times
this cycle may have to be repeated several times.
One problem with this approach is that the tissues
may not tolerate the ischemia for the length of time
needed to finally stop the bleeding. This is why some
authors only inflate for a few minutes at a time in
order to allow reperfusion of the tissue in-between
inflations, even though additional bleeding may
occur during the deflation periods. Although longer
inflation times maybe associated with less bleeding,
intraluminal thrombus can form while the balloon
is arresting blood flow [20].
In some cases the dai
patency cannot be sac
7.5.3.2
Uncovered Stents
Standard uncovered
stents can occasionally be
used to seal a vascula
r defect [21] (Fig. 7.6). While it
seems counterintuitrv
e that a bare stent would seal
an arterial leak, this
can work if the defect runs
laged artery is critics
ificed. Thus alternate tech- obliquely through the arterial wall. In this setting,
Fig. 7.(i. a Hepatic ;i:':ci'iijgi".i;Vi in ;'. pa:ie:i; who developed needing sev-
jf'.e: J VV-',i.'L\r ope:a;ion. A nseudoaneurvsm iiinf". i is seen
where the gastroduodenal artery was resected. l> A balloon occlusion
catheter (iiiTpir! was inflated across die arterial derec- to tamponade
bleeding until a decision was T.ace retarding cehniiive therapy, c A
bare balloon expandable stent [iinvn-~) was placed across the arterial
defect with plans to pass microc.oils throng;: the sir:'/; however, tins
ladv si; owed I hat die ane::al d erect had been sealed by the
overed stent alone
the expanded stent forces together the two sides
of the oblique tear, thus sealing the defect. This
maneuver is a little risky since it can be difficult to
tell whether the tear runs obliquely through the arte-
rial wall. If it does not, placing a stent may simply
hold open the defect and promote continued hem-
orrhage. However if the stent by itself does not stop
the bleeding, the stent can be used as a gate to trap
coils out in the pseudoaneurysm. A catheter can be
passed through the stent interstices allowing coils to
be deployed out in the pseudoaneurysm.
7.5.3.3
Stent Grafting
A potentially simpler and more secure method is
deployment of a stent graft across the arterial defect.
There are currently several commercially available
stent grafts. Some, like the Fluency (Bard Periph-
eral Vascular; Tempe, AZ) and the Viabahn (W.L.
Gore; Flagstaff, AZ) have a polytetrafluoro ethylene
(PTFE) layer that would seal the hole in the vessel
wall. The Wallgraft (Boston Scientific) has a woven
Dacron graft material and although this is more
porous, it will still effectively seal a hole and prevent
further bleeding.
Currently most of these devices are fairly large
and are best suited for repair of larger vessels such
as subclavian, iliac, femoral, or splenic arteries
(Fig. 7.7). There is also a smaller stent graft origi-
nally designed for coronary applications, the Jostent
( lomed; Helsinghoiy, Stvedt-n), Ilia! lias been i i s r- ■::! in
smaller hepatic and renal arteries [17, 22-28]. Cur-
rently this device is still in trial and is not readily
available in the United States. It is important with
all these devices to carefully match the device diam-
eter to the vessel diameter. Choosing a device that
is too small for the vessel will yield a poor seal and
potentially could allow continued hemorrhage. On
the other hand with the Viabahn, if the device is
significantly over-sized for the vessel, some of the
graft material will fold into the device lumen and
may compromise blood Hove.
Fig.7.7. a Injection of a s'jbchivijn she.\t:'. Uiai had been placed on the ward
and was later found to have pu.s.il lie blooi flow coming out of the sheath. The
sheath {arrow) enters die s : abclav;an ,ine:y and had been accidentally advanced
up into the right vertebral artery, b Righi biach.ocephakc arteriogram after
removal of the mis. "laced ■=:■_ eiii h shows :apid com;as: extravasation/ bleeding
(arrow) from the subchivian .u te: y puncture site. A VV:ilJgrp.ft has been partially
deployed prior to removing I lie sheath, c A fie: teposiitoning the Wallgraft, the
arterial defect has been sailed. The gr.tfi does noi compromise the carotid but
does occlude the vet trbr.il aitetv, which wns well c/erft.sed from the contralat-
7.6.1
Hepatic
Hepatic iatrogenic bleeding can be divided into
intrahepatic and extrahepatic varieties. Intrahe-
patic bleeding and pseudoaneurysms can result
from any of the interventional hepatic procedures
including percutaneous biopsy, transjugular biopsy
[29], percutaneous biliary drainage or stenting, and
even transjugn btr int in hepatic portosystemic shunts
(Fig. 7.8). Extrahepatic lesions are often postsurgi-
cal in nature due to injury to a vessel or breakdown
of a vascular anastomosis. Extrahepatic lesions
may cause pain by mass effect and may be more
likely to cause hemoperitoneum since they have
less surrounding tissue to help contain the bleed-
ing. Intrahepatic lesions are more likely to cause
pain or hemobilia but may go undetected for a long
time, with some patients not presenting until several
months after the injury [30].
The locations also tend to dictate the therapy
used. Since intrahepatic lesions often involve a
peripheral branch, the artery can generally be sac-
rificed. Thus when the lesion can be reached with
a catheter, standard coils or Gelfoam embolization
is usually the primary therapy. Embolization of
intrahepatic lesions is usually highly successful. In
one study [31], hemobilia was controlled in 100% of
eight cases. Hidalgo et al. [30] controlled hemobilia
in 11 of 12 patients, however, several of the patients
had recurrent bleeding 2 weeks to 2 months later.
Although Tessieret al. had a success rate of only 86%
for embolization, they noted that mortality was only
14% in patients treated with embolization but was
25% after surgery [32]. Results of direct puncture
have been very favorable with effective occlusion
of the lesions; however there are no large series and
only scattered case reports of treating hepatic and
pancreatic lesions with this technique [8, 9, 33-35].
One recurrence 2 months after initially successful
direct puncture embolization hs
[8].
Extra-hepatic pseudoaneurysm
treated with coil embolization sin
fice a major branch to a lobe or evt
Successful percutaneous thrombin
anastomotic pseudoaneurysm has been described
[12]. Recently, a number of case reports have been
published on the use of stent grafts to repair these
i been reported
a the entire liver,
l injection of a
Fig. 7.8. a Arterial phase of a hep;
study shows prominent oparifical
shows rapid flow into the bile dui
arterio -biliary fistula
: arteriogram in ,1 .\me::: w:t!i hemobilia ? days after T!PS. b L : -. t e r passe of the same
■n of the bile edicts, e Magitifie;: supei-selec live .i] :ec ii-gi ;"un Ui rough ;'. micro catheter
; from this arterial branch, d Pos:-cmbolizaiic::i a: reriogr.ir.i show:; no further flow to t
extra hepatic lesions [27, 28, 36, 37]. While successful
in all cases, larger series are needed to validate this
technique.
7.6.2
Renal
Pseudoaneurysms or arteriovenous fistulas occur
after 0.2-2% of biopsies in transplant kidneys. Simi-
larly after percutaneous nephrostomy the incidence
of significant arterial injury is around 1%. Although
vascular injuries typically manifest within the first
week or so, delayed presentations out to 21 months
after initial nephrostomy have been reported [38].
Although most papers report only a few patients [39,
40], embolization is well accepted as the preferred
method to deal with vascular injuries after r
biopsy and nephrostomies [41].
Technical success of embolization for
vascular injury is quite high, around 95-100% [42-
44] . Typically the recurrence rate is nearly 0%; how-
ever, in one series a second embolization session was
needed in2 (15%) of 13 patients to fully occlude arte-
riovenous fistulas and achieve true technical suc-
cess [44]. An analysis of the effect on renal function
of selective embolization for traumatic renal lesions
revealed that the mean volume ol infarcted kidney
was only 6% (range 0-15%) and 1 weekpostemboli-
zation the serum creatinine was normal in all their
patients [42]. A series of renal transplants estimated
that the maximal volume of infarcted kidney after
embolization for biopsy-related injuries was always
less than 30% [44]. Also, while renal function dete-
riorated in three patients, the serum creatinine sig-
nificantly improved in 10 of 13 (77%).
The incidence of rupture after renal PTA has
ranged from 1.6% to 5%. This is clearly a situation
where traditional embolization is undesirable since
it will lead to infarction of the entire kidney. How-
ever, if the patient is not a surgical candidate and
they have another well functioning kidney, embo-
lization with sacrifice of the kidney can be used
as a life-saving maneuver if no other options are
available. Stent graft use in the renal arteries has
been described in a number of small case reports
[17, 22-26, 45, 46]. They have been mostly used for
exclusion of renal aneurysms but have occasionally
been used to treat ruptures. In a series of five renal
ruptures [17], all were able to be managed nonsur-
gically. Some were treated by balloon occlusion
alone but one patient required a stent-graft. The
stent-graft used in this setting was a home-made
device of thin-walled PTFE mounted on a Palmaz
stent. Another patient had a second bare stent
placed within the original stent that caused the
rupture, and this was followed by 2 minutes of bal-
loon tamponade with successful sealing of the leak.
There are no good series with long-term follow-up
reported; however, a trial with 12 renal stent grafts
showed reasonable patency with a restenosis rate of
only 7.3% at 6 months [23].
7.6.3
Miscellaneous Injuries
Outside of the liver and kidneys, there are innu-
merable other types of iatrogenic arterial injuries
that can occur. Of course the commonest iatro-
genic injury is post-catheterization femoral artery
pseudoaneurysms, but this is discussed in another
One type of injury that maybe increasing in fre-
quency (due to the increased use of central venous
lines} is damage to the subclavian or carotid arter-
ies or branches during line placement. If the injury
involves a small artery such as a thyrocervical
branch, selective embolization will typically solve
the problem. If the subclavian artery itself is punc-
tured or has a catheter placed into it, management
becomes more difficult. Surgical repair carries
high risks and may even require a thoracotomy,
whereas standard embolization is not practical
because of the arm ischemia it would cause. Plac-
ing a stent-graft is probably the preferred way to
deal with this, assuming that the arterial defect is
in a location that allows a graft to be placed without
compromising the carotid artery. In fact, the first
reported application of an intravascular stent graft
was to close a large hole (10 Fr) in the subclavian
artery caused by an improperly placed Port cath-
eter [47].
Arterial rupture is a feared complication of iliac
PTA but fortunately is uncommon, with a 0.2-0.4%
incidence [18]. However when it does occur it can
be life-threatening, with the patient rapidly becom-
ing hypotensive. This kind of injury has tradi-
tionally been managed surgically. Embolization
is not typically done since it will likely make the
leg severely ischemic. However embolization can
be combined with a femoral- femoral cross-over
graft. This type of graft has lower patency than
a direct aortofemoral bypass, however it can be a
useful option inpatients who are high surgical risks
since it is an extra-abdominal operation and can be
accomplished without general anesthesia. It does,
however, require that there is good inflow into the
opposite iliac artery. With the increasing availabil-
ity of commercially available covered stents, stent-
grafting is now considered by some to be the treat-
ment of choice [48].
Embolization techniques have been applied to
iatrogenic hemorrhage throughout the entire body.
There are numerous case reports of embolization
successfully terminating bleeding after a wide vari-
ety of operation or procedures as varied as prosta-
tectomy [49], orthopedic osteotomy [50], salpingo-
oophorectomy [51], bone marrow biopsy [52], and
pelvic abscess drainage [53]. Kwon and Kim [54]
reported a particularly large series of 24 cases of iat-
rogenic arterial injuries in the uterus after curettage
or cesarean section. Gelfoam embolization of the
uterine arteries successfully stopped bleeding in all
cases. Interestingly, four patients desired to become
pregnant after undergoing bilateral uterine embo-
lization, and all four were able to deliver full-term
babies. A theme running through all these reports is
successful cessation of bleeding with no or minimal
complications, enforcing the idea that embolization
shou Id be the first approach to treat iatrogenic arte-
rial hemorrhage.
Arterial puncture site complications such as hema-
toma, pseudoaneurysm, arteriovenous fistula, dis-
Ml'', rurcy
section, and arterial occlusion can all certainly
occur but are not unique to embolization cases.
Trauma from the catheters and guidewires can also
cause spasm or dissection in the main trunk or
branches leading to the arterial defect that one is
attempting to treat. This can prevent being able to
advance the catheter to the bleeding site, or if the
catheter can be advanced beyond the spasm / dis-
section there may be no flow to carry flow-directed
embolic particles more distally. Spasm by itself may
decrease blood flow to the arterial defect sufficiently
that the bleeding will stop. However, this is a less
secure method of managing the iatrogenic lesion.
If the spasm resolves, bleeding may recur once the
injured segment is again subjected to normal arte-
rial pressure. Also any pseudoaneurysm or fistula
would not be directly occluded and the permanence
of the occlusion of that lesion would be questionable.
If there are any collateral communications beyond
the spasm or dissection, the pseudoaneurysm would
likely remain patent.
If spasm occurs, local injection of vasodilators
(e.g. 50-100 microgram boluses of nitroglycerin}
may relieve the spasm. The best approach is to try
to avoid the spasm in the first place. Minimizing the
manipulation of guidewires and being very gentle
will help reduce spasm. Also if it is anticipated that
advancing the catheter will be difficult, prophylac-
tic boluses of nitroglycerin can be employed. If dis-
section occurs, it may be possible to tack down the
flap with a stent or PTA depending on the location
and the caliber of the artery.
As emboli are being delivered to the target, the
next complication that may be encountered is non-
target embolization. When using flow-directed
emboli such as Gelfoam or PVA, overly vigorous
injection can lead to reflux of emboli out of the
target artery. The risk of reflux is increased as the
end of the embolization approaches, since there will
be increased resistance to flow in the target artery.
The chance of particle reflux can be minimi/cd by
gentle injection, having the emboli suspended in
contrast, and careful fluoroscopic monitoring of the
injection.
Nontarget embolization can also occur when
using coils. Rarely do coils migrate to a remote
location, but they can cause undesirable occlusion
of arteries or branches adjacent to the target vessel
(Fig. 7.9). Having the catheter securely positioned
well into the target artery before pushing out the
coils will help prevent nontarget embolization.
However it is not always possible to have the cath-
eter advanced well into the target artery, especially
if the injury is close to the vessel origin. Maintain-
ing good manual control of the catheter close to the
groin access will allow one to move the catheter in
or out slightly to help form the coils in situ. A gentle
tapping motion ofthe pushing wire will also help the
coil to form in a tight configuration. Rapidly push-
ing the coil out often elongates the coil and forces
the delivery catheter back out ofthe target artery.
Choosing appropriately sized coils is also critical
to prevent this complication since pushing in over-
sized coils will also tend to back the catheter out of
the target artery.
If a coil does get misplaced, retrieval with snares
can be attempted. This can be quite difficult since
the errant coil may often wedge itself into the periph-
eral aspect of another branch. That plus the spasm
that frequently occurs from excessive manipula-
tion makes it difficult to open a snare sufficiently to
get around the coil. An unusual form of nontarget
embolization is delayed migration of coils from the
original point of deployment into another structure.
Coils placed in an intrahepatic pseudoaneurysm
have been reported in two cases to migrate (pre-
sumably via erosion of the adjacent structures) into
the bile ducts [8, 55]. In these cases biliary obstruc-
tion resulted and required percutaneous or surgical
removal of the coils.
Tissue infarction can range in severity from an
expected inconsequential occurrence up to a fatal
complication. When embolizing end-arteries such
as renal branches, it is expected that the paren-
chyma distal to the embolized segment will infarct.
However if the embolization is done peripherally
enough, only a small segment of the kidney will
infarct with no effect on renal function, and some-
times it will cause only minimal symptoms (pain
and fever). In the liver, the consequences depend
partially on the degree of intrahepatic collateral
flow beyond the embolized artery. Hashimoto et
al. [31] found that no hepatic infarction occurred
when there was good collateral flow, but all four
patients w it li poor collateral ( low dt-veloped infarc-
tion. Three of these four had no symptoms and had
infarcted segments seen on CT scans done to eval-
uate transient transaminase elevations. However,
one patient did progress to hepatic failure. Such
severe ischemia is uncommon in embolization for
iatrogenic bleeding but has been reported by others
[30]. Clinically significant ischemia can be mini-
mized by super-selective embolizations with 3 Fr
catheters and by avoiding the use of very small par-
ticles or liquid embolic agents that penetrate out to
the capillary level.
Fig. IS. a CT of a 38-year- ok. female who had rank pain after a pai tiai nephrectomy. A hematoma and a pseudoaneuiysm
iiiMiiu 1 ) a iv seen, b Lefi renal arteriogram shows a pseucoai'.e'.u ysm near the origin o: the inle: ioi brunch of the rein I artery,
c Coils were placed distal and into the pseud' '.lnetuvsm, ai'd an aticmp: was made to p'ac^ the final coils iust proximal to the
pseud oaneuiysm. These last coils moved oc.i into ihe main renal ai ierv occiuding ah rena! artery ~ow. d An ai ie: iogram done
3 months later shows some recanali nation tun 'Ugh iiie displaced coils with some perfusion to the kidney
Future Development and Research
Areas for potential research include development of
new embolic a^etits and improving enisling embolic
devices. Gelfoam and PVA are less than ideal embolic
agents. Some of the newer embolic agents such as
Embospheres (Biosphere Medical; Rockland, MA)
maybe more easily injected through small catheters,
but they also may be more prone to causing tissue
ischemia since they can travel more peripherally.
Studies will need to be done to see whether this
agent is appropriate for treating iatrogenic bleeding
and to determine what size spheres should be used.
Liquid agents have some potential benefits in terms
of ease of use and control. The initial studies with
NBCA [16] are a step in the right direction, but some
of the other new liquid embolic agents will also need
to be evaluated.
Nontarget embolization can ruin an otherwise
good result and while coils are one of the most com-
monly used embolic devices, they can be difficult to
form properly. Better control over the coils is desir-
able. The Guglielmi detachable coils (Target Thera-
peutics; Fremont, CA) do provide the ability to redo
the deployment if it is unsatisfactory, and they have
night
been applied to closure of iatrogenic vascular lesions
[56]. However, they are expensive and the electro-
lytic detachment is more complex than the use of
standard coils. There should be investigation into
new embolic devices with better control and possi-
bly different shapes that might enhance both place-
ment and control of bleeding.
Although stent-grafting is an increasingly attrac-
tive therapy for some cases of iatrogenic bleeding,
smaller, better devices and more ready availability
are necessary. Bifurcated or fenestrated devices sim-
ilar to those developed for aortic aneurysms i
widen the application of visceral stent-grafts,
the presence of critical side branches s
limits the use of stem-sratts.
Conclusion
Embolization has become one of the primary tech-
niques for tre.nina utrogriik" bleed ma- However since
by default it causes vessel occlusion, it is mostly appli-
cable to small, less important arteries or in periph-
eral branches that can be readily sacrificed. Proper
technique generally allows a high degree of clinical
success with minim;! I risk. With the ongoing develop-
ment of stent shifts, end avascular treatment may also
become the primary means of repairing larger, more
critical vessels that must remain patent.
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Visceral Aneurysm
8 Embolization of Visceral Arterial Aneurysms
Craig B. Gla
Introduction 99
t' :■ L l'. :: ■ p h y ■= : -.:i J .;: g y 100
Clinical Considerations
Anatomy 103
Technique 104
Hepatic 1 05
Incidence !05
Causes 105
Risks Posed by the ,
Management 106
.1 Anatomic/Physiologic Consider
.2 Technique 106
.3 Results of Embolization 106
.4 Complications 106
Splenic 107
Incidence 107
Risks Posed by the Aneurysm
Management 107
.1 Anatomic/Physioiogic Consider
.2 Technique 107
.2 Results of Embolization 108
.3 Complications 109
Mesenteric 109
Incidence 109
Causes 111
Risks Posed by the Aneurysm
Management 111
.1 Anatomic/Physioiogic Consider
.2 Technique 111
.3 Results of Embolization 112
.4 Complications 112
Renal 112
Incidence 112
Causes 112
Risks Posed by tht
C. B. Glaibebman.MD
Ins true tor, promoted to assista:'.: professor of radiology, Radi-
ology. Division of interventional Kaoiology, Washington Uni-
versity School of Medicine, Mallntckrod; Institute of Radiol-
ogy, 510 S. Kings highway, St. Louis, MO 63110, USA
M. D. Dahcy, MD
Professor, Rjdiologv -.in-." '•urgeiv I o vision oi I" 1 i a gnostic Radi-
ology, Chief, Intervention.! I Radiology Section, Washington
University Sch' >ol ■ if Medicine, KLiKincltrodt Iiisiilute of Radi-
ology, 510 S. Kingshighway Blvd. St. Louis, MO 63110, USA
M.ui.'geinent 113
Aii.ilomic/Phvsiologic Considerations
.9.4.2 Technique 113
.3 Results of Embolization 113
.4 Complications 113
Complications 114
Future Development and Research 114
Conclusion 115
References 115
Introduction
Visceral arterial aneurysms (VAAs) are rare with
incidence rates ranging between 0.01% and 0.2% at
autopsy. However, they are important entities to rec-
ognize due to disastrous outcomes that result should
rupture occur. Most visceral aneurysms are asymp-
tomatic and are either overlooked clinically or found
incidentally. Roughly 25% of symptomatic patients
with VAAs will present with rupture [1]. Depending
on the literature, reported mortality rates of rup-
tured aneurysms range from 10% to 50% [1-4]. It is
important to note that aneurysm location contrib-
utes to the varying morbidity and mortality.
VAAs occur in the splenic, hepatic, superior mes-
enteric, gastroduodenal, pancreaticoduodenal, and
renal arteries. Classically, splenic arlerv aneurysms
have been found to account for 60% of all VAAs.
Interestingly, Shanley et al. reviewed the litera-
ture from 1985 to 1995 and found that hepatic artery
aneurysms were more common [5]. This finding
may reflect an increase in the number of percuta-
neous hepatic and biliary interventions being per-
formed. Furthermore, the routine use of computed
tomographic imaging after trauma also attributes to
the increased discovery of hepatic artery pseudoan-
eurysms. Because VAAs occur infrequently, it must
be remembered that much of the current literature
consists of retrospective reviews of small cohorts
that span as many as 10 to 15 years of experience.
Therefore, much of what has been reported is either
anecdotal or based on collective case reports.
lan and M. D. Darcy
A brief review of our experience over the last two
years demonstrates that our group has embolized
21 VAAs. By far, the majority of cases (nine) were
performed urgently for traumatic liver and splenic
lacerations. This was followed closely by seven iatro-
genic pseud oaneurysms that were caused by percuta-
neous biopsy, biliary intervention, or from previous
laparotomy. Three pseud oaneurysms resulted from
inflammatory causes such as pancreatitis, divertic-
ulitis, and peptic ulcer disease. Two aneurysms were
treated in patients with aagiomvolipomas. A vari-
ety of techniques including coil, Gelfoam, and PVA
embolization were used. No stent grafts were placed
in this time period. Immediate technical success
was achieved in all cases; however, the long-term
outcomes are currently unknown.
Historically, visceral aneurysms have been treated
surgically by resection, ligation, and bypass, as well
as vein patch angioplasty. Today, the interventional
radiologist is particularly well suited to perform
e forms of treatment with high techni-
s and less patient morbidity. VAAs have
been treated with transcatheter techniques such as
coil embolization, thrombin injection, or stent graft
placement. Although the literature is relatively scant
regarding the long-term outcomes of embolization
or stent graft placement, the trend has been toward
minimally invasive therapies. Preemptive treat-
ment of these lesions with percutaneous methods
has become more popular due to the high mortality
associated with rupture and the reduced morbidity
that embolization procedures offer.
Pathophysiology
The arterial wall is composed of three layers. The
outer serosal covering is the adventitia, the muscu-
lar middle layer is the media, and the inner lining is
the intima. True aneurysms are distinguished from
false or pseudoaneurysms based on which layers of
the arterial wall are present in the aneurysm itself.
In order to classify an aneurysm as being "true," it
must be comprised of all three layers. Pseudoaneu-
rysms have any combination less than all three of
the arterial wall components.
Aneurysms can be either saccular or fusiform.
Saccular aneurysms are typically spherical in shape
and have a small communication or "neck" arising
from the parent vessel (Fig. 8.1). Fusiform implies
longitudinal dilatation along the course of the
artery. True fusiform
s ofv
place for a tusitorm
aneurysm to occur is in the superior mesenteric
artery distribution; it is typically the result of post-
stenotic dilatation from atherosclerotic disease.
More commonly, VAAs are saccular pseudoaneu-
rysms resulting from an insult to the arterialwall. His-
torically, one of the most common causes of saccular
aneurysm formation has been from bacterial endo-
carditis. Originally described by Osier, aneurysms
caused by an infectious etiology have been termed
mycotic. Direct infection of the vaso vasorum in the
adventitial lining lias been postulated as a cause of
mycotic aneurysm formation. The resulting inflam-
matory response typically results in saccular pseu-
doaneurysm formation. The incidence of this type
of aneurysm has diminished over time due to ear-
lier detection and treatment with antibiotics. Today,
mycotic aneurysms in the presence of endocarditis
have a high association with intravenous drug abuse
and can occur in visceral and peripheral arteries.
Similarly, adjacent intlammatorv changes such
as pancreatitis can cause compromise of vessel
wall integrity. Proteolytic degradation can occur if
pancreatic enzymes come in contact with arteries.
Gastroduodenal and pancreaticoduodenal pseu-
doaneurysms are especially prone to rupture in the
presence of duodenal ulceration, pancreatitis, or
pseudocyst formation [6, 7]. These should be treated
regardless of size.
L' A
Fig. 8.1. Large saccuhir pseudooneurysni .; rising from a sig-
moid branch of the IMA demonstrating a short, well-defined
neck. (Courtesy of Jennifer E. Gould, MD)
Embolization of Vis!
Other causes of saccular aneurysm formation
include trauma and iatrogenic injury from percu-
taneous or surgical interventions. Any focal insult,
perforation, or laceration can lead to pseudoaneu-
rysm formation. These aneurysms are often symp-
tomatic due to hemorrhage, pain, and hypotension
that occur. Iatrogenic injuries will be discussed in a
separate chapter of this text.
Multiple saccular microaneurysms are com moiilv
seen with vasculitis caused by polyarteritis nodosa
(PAN). Amphetamine abuse can also lead to multiple
renal and hepatic microaneurysms similar to those
seen with PAN. The small size and diffuse nature of
these lesions often precludes embolization.
Inherent weaknesses caused by acquired or con-
genital etiologies may lead to VAAs. Congenital
weakness of the arterial wall from a collagen dis-
order such as Ehlers-Danlos or Mar fan's Syndrome
can result in either saccular or fusiform aneurysms.
Ansi ography should not be performed in patients
with Ehlers-Danlos due to the high risk of arterial
rupuire.Therek're.eniraolmihoii'.vould be extremely
dangerous to execute in these patients.
Fibromuscular dysplasia (FMD) is an inherent
arterial wall abnormality that classically affects
the media of the renal arteries and can be associ-
ated with renal artery aneurysms. Several subtypes
of FMD have been described and the disorder can
affect other medium-sized vessels including the
carotid, vertebral, brachial, and visceral arteries.
For the angiographer, FMD has the classic beaded
appearance often described as a "string of pearls."
Both aneurysms and dissections can be seen with
this disorder. The treatment for [-'MP is angioplnstv
of the intraluminal webs, which results in signifi-
cant remodeling.
Renal artery aneurysms can also be seen in
patients with an^iomyolipomas (AMI.s) (lig.8.2}.
Classically, AMI.s occur in elderly females and
patients wiih tuberous sclerosis. The enure lesion
can often be cmboh/ed in addition to coiling the
aneurysms, A combination of coils and PVA or
simply ethanol infusion wtrh a balloon occlusion
catheter can be performed as definitive treatment
or if surgical resection is anticipated.
Although atherosclerosis has been implicated,
there is debate as to whether it is the cause or the
result of aneurysm formation. The heavy calcifica-
tion seen in splenic artery aneurysms may be due to
altered hemodynamics. For example, splenic artery
aneurysms can be seen with portal hypertension
(Fig. 8.3). Saccular or "berry" aneurysms associ-
ated with hypertension and atherosclerosis arise at
Fig. 8.2. Seleiiive r;gln renal iiiiiiogrrun denianslialins; :. huge
AML with aneurysms thai di-phces die kidney Literally and
:aipe: ioi ly. Tae p.meiil has tuberous sclerosis
branch points where intrinsic weakness of the wall
may exist.
Aneurysm configuration should influence
treatment planning. Proximal and distal control
should be obtained if the aneurysm itself cannot be
occluded.lt is typically easier to occlude short necks
seen with the saccular form; therefore many differ-
ent treatment options exist. These will be discussed
later in the chapter. Fusiform aneurysms may not
allow for both proximal and distal control and are
often better treated with surgical ligation or recon-
struction.
Clinical Considerations
Ap propria
patient work up inclui
of current and past medical history,
pertinent imaging, a limited physical exam with
evaluation of the pulses, and basic laboratory
parameters. Endocarditis, vasculitis, pancreatitis,
prior trauma, and congenital arteriopathies such as
Ehlers-Danlos are important entities to be aware
of. Knowing the past surgical history and whether
prior percutaneous biopsy was performed would be
relevant for iatrogenic causes. Since asymptomatic
patients have VAAs that are often discovered inci-
dentally and symptomatic patients often have vague
C. R. GkiibenuanandM. D. Dar
Fig. 8.3. a Ceikk" .;:-giog:';iiii in ;i p.itienl wi;h pciLiil !;ype:t
demonstrating a dist.ii sp'r:iic lii l^:y aneurysm, b Celiac angiogram
from another patient with nr.iluple spienk" aneurysms associated
with portal hypertension who ha- .mo er gone liver transplantation.
Note the iarge hepa:io psc.idoaneuiysni ;usl medial to the upper
pole of the right kidney, c ?eleo:ive oommon hepatic artery injec-
tion in the patient from b
abdominal pain, CT or MR imaging has typically
been performed looking for other etiologies prior to
referral to the Interventional Radiologist. Reviewing
the images and examining the patient in the Inter-
ventional clinic are important steps in formulating
a successful treatment plan. A complete blood cell
count, prothrombin time with INR, and a basic or
complete metabolic profile should be available prior
to the procedure. Acceptable lab value limits vary
depending on the institution.
Diabetics and patients with borderline renal func-
tion should be prehydrated to reduce the chances of
contrast-induced nephropathy. A recent randomized
controlled trial suggested that prehydration with
sodium bicarbonate is more effective than sodium
chloride in preventing contrast-induced renal failure
[8]. For those patients with contrast allergies, prophy-
lactic steroids are typieallv administered at least 12
hours prior to intervention. If access from a brachial
artery is required, a pre-procedure neurologic exam
including mental status is vital to document any
change during or after the procedure since catheters
will cross the origin of at least one cerebral vessel.
Ideally, monitored conscious sedation should be
administered by a registered nurse with intensive
care experience or training. Continuous assessment
of vital signs and oxygenation is important to main-
tain a comfortable level ot sedation without respira-
tory or cardiovascular suppression. Typically, fast-
onset, short-acting agents are used. In our practice,
we use a benzodiazepine such as Versed (Roche
Pharmaceuticals, Manati, PR} and the narcotic
analgesic Fent a nyl (Suhlmsaze; Abbott Laboratories,
North Chicago, PL).
Embolization of Vis!
Patients with active bleeding should be vigor-
ously transfused to maintain hemodynamic sta-
bility, and there should be no delay in transporta-
tion to the angiography suite for treatment. Severe
coagulopathy should be corrected with fresh frozen
plasma and platelet transfusion because hemor-
rhage can persist despite a technically successful
embolization. Coagulation factors are required
to maximize the effectiveness of the emboliza-
tion materials and are responsible for the ensuing
thrombus at the site of embolization. Plasma can
infuse throughout the procedure, and the need
for transfusion should not delay treatment if the
patient is actively bleeding.
Periprocedural antibiotics should be considered
if end-organ ischemia is a possibility. This is more
common with the small permanent agents such as
PVA and in organs where there is poor collateral flow.
Tissue necrosis and hematoma can lead to abscess
formation. When total occlusion of the splenic
artery occurs and infarction results, patients should
receive the pneumococcal vaccine. They should also
take prophylactic antibiotics for future procedures
as if they underwent a surgical splenectomy.
At our institution, outpatients are typically
observed overnight and hematocrit levels are
checked to watch lor 1 postprocedural complications.
Postembolization syndrome consisting of pain,
fever, and nausea can be seen in the first 24 hours
following intervention. Follow-up Doppler ultra-
sound can be used to assess the success of emboliza-
tion. However, the timing and frequency of reimag-
ing are debatable. There are reports in the literature
demonstrating that recanalization of treated aneu-
rysms can occur.
For those patients who present emergently and
require fluid and blood product resuscitation, trans-
fer to the intensive care unit for close monitoring is a
must. If coagulopathy exists, or there is concern for
further bleeding, the sheath can be left in the access
site should there be need for repeat angiography and
embolization.
8.4
Anatomy
It is vital to understand the arterial anatomy and
know the vascular supply distal to the planned
embolization. In some VAAs, tissue ischemia can
occur if the parent vessel is completely occluded.
However, if good collateral flow exists, such as in
the stomach and duodenum, permanent emboliza-
tion of entire vessels can be performed with some
degree of impunity.
The hepatic and splenic arteries typically arise
from the celiac axis, which has its origin at the T12/
LI level of the abdominal aorta. The three main
branches of the celiac include the splenic, left gas-
tric, and common hepatic arteries. The splenic
arterv is typically large and tortuous and sup-
plies small branches to the pancreas. The common
hepatic branches into the gastioduode nal and proper
hepatic arteries. There is significant variant anat-
omy of the hepatic arteries that the interventionist
should be aware of. The most common variation is
the replaced right hepatic artery, which arises from
the superior mesenteric artery (SMA). This occurs
in 12%-15% of the population. Other less frequent
variations include the replaced left hepatic from the
left gastric artery (11%) and the completely replaced
common hepatic from the SMA (2%).
The gastroduodenal artery arises from the
common hepatic artery and supplies branches to
the pancreatic head via the superior pancreatico-
duodenal arcade (SPDA) and greater curvature of
the stomach via the gastroepiploic. It is an excellent
collateral vessel connecting the celiac to the SMA if
either one becomes occluded.
The SMA arises at the LI level and supplies the
small bowel via jejunal and ileal branches, the right
and middle colon via the ileocolic, right and middle
colic arteries, as well as the pancreatic head via the
inferior pancreaticoduodenal arcade (IPDA).
The inferior mesenteric artery (IMA) arises from
the aorta at the level of the left pedicle of L3 and sup-
plies the left colon, sigmoid, and rectum. It is fre-
quently occluded in older populations. Collateral
flow to this distribution can come from the mar-
ginal artery of Drummond or from branches of the
internal iliacs.
The renal arteries originate from the aorta at the
L2 level. A third of the population has multiple renal
arteries. The main renal arteries are 5 to 6 mm in
diameter and typically bifurcate into anterior and
posterior divisions. There is further subdivision
into segmental, interlobar, arcuate, and interlobular
arteries before termination in glomeruli. Capsular
and adrenal arteries take their origin from the main
The concept of collateral and end-organ vascu-
lar supply is vital to understand when considering
embolization of visceral vessels. Choice of embolic
agents for these vascular distributions and applica-
tions is described elsewhere in this book.
n and M. D. Darcy
Technique
After arterial access is obtained, a sheath with hepa-
rinized saline flush through the side port should
be placed to maintain access throughout the case.
Typically a 5 or 6 French short vascular sheath such
as a Flexor Check-flo (Cook I no, Bloomington, I N)
is used. Sometimes sheath upsi/c or exchange is
required based on the arterial anatomy or type of
intervention to be performed. Hoi example, guiding
catheters such as a Balkin Up and Over (Cook inc.)
may offer the advantage of a more secure access
around corners during coil deployment. Certain
devices such as stent grafts may mandate the use of
larger sheaths for delivery.
Catheter selection is based upon individual pref-
erence and experience, but is typically guided by
patient anatomy. It is often wise to perform a non-
selective aortogram with a pigtail catheter (Merit
Med ical Systems Inc., Salt Lake City, UT) to identify
vessel origins, assess patency, and look for potential
stumbling blocks such as variant anatomy or ste-
nosis from atherosclerotic disease. A reverse curve
catheter such as a Sos (A ngiodynamics Inc., Queens-
bury, NY} can often be used to select visceral and
renal arteries. A floppy tipped wire, such as a Bent-
son (Medi-Tech/Boston Scientific, Watertown, MA)
is used to select visceral branches and advance the
catheter into the origin to perform selective angi-
ography. Other catheter considerations include the
Simmons (Cook Inc.), Roche Celiac (RC-1) (Roche
Inc., Indianapolis, IN), Cobra (Merit Medical Inc.,
South Jordan, UT), Rochelnferior Mesenteric (RIM)
(Cook Inc.), or even a Multipurpose Angiographic
Catheter (MPA) (Cook Inc.) if approaching from
the arm. Often, the coaxial use of microcatheters is
advantageous when attempting to occlude vessels as
peripherally as possible. Being as selective as pos-
sible is important when embolizing tissues that have
poor or no collateral supply.
In our experience, the Sos catheter can be used
to select the origin of nearly every visceral vessel
including the renals. Once selective angiography is
performed and access is secured by passing a wire
distally, the Sos can be exchanged for a more appro-
priate catheter to fit the anatomy, or a microcatheter
can be used coaxially through the Sos. Hydrophilic
coated wires and catheters are useful for navigating
tortuous vessels. The secondary curve of the Cobra
catheter can help to select more peripheral branches
as well as provide a "backstop" to keep it from buck-
ling out of the origin of the desired vessel.
Another trick is the formation of a Waltmanloop
if a reverse curve catheter is unavailable or unsuc-
cessful at cannulating the origin of visceral arter-
ies. This is typically termed over the aortic bifurca-
tion with the tip of a Cobra or hockey-stick catheter
in the contralateral external iliac artery. Using the
back end of a Bentson wire, the loop is formed by
pushing cephalad and twisting. The back end of the
wire must be positioned in the ipsilateral common
iliac segment of the catheter to provide the stiffness
required to advance the entire loop into the distal
aorta. The wire is then reversed so that the floppy
tip can be used to select the desired vessel origin.
An alternative way to form a Waltman loop was
described by Sh husky- Goldberg and Cope and uses
a stitch and guidewire combination to physically
pull the catheter into a reverse curve formation [9].
Prior to intervention, selective angiography of
the target vessel is performed. Access is secured and
tested bypassing a wire through the catheter to ensure
that it does not buckle out of the origin and lead to
nontarget embolization. Permanent occlusion is the
goal of treatment for VAAs due to high morbidity and
mortality should they rupture. Permanent materials
include, but are not limited to, coils, thrombin, glue,
and stent grafts. Distal to proximal embolization
should be performed to prevent recanalization of the
aneurysm from retrograde flow through collaterals.
If the aneurysm neck is amenable, packing with coils
can be performed. Care must be taken not to rupture
the aneurysm with this type of intervention, which
is far more challenging and time-consuming than
smsplv embolm ni; the supplying vessel.
If both distal and proximal occlusion cannot be
obtained because the aneurysm neck is too close to
a vessel origin or distal occlusion would result in
undesirable end-organ ischemia, a bare metal stent
can be deployed across the neck of the aneurysm. A
guidewire is then passed between the interstices of
the stent and into the aneurysm sac. Selective coil
embolizationofthe aneurysm can then be performed
using a microcatheter and microcoils. Alternatively,
a stent graft can be considered for this situation.
Due to the small size and tortuosity of the vis-
ceral vessels, stent graft placement is often prohibi-
tive. In the appropriate situation, stent grafts offer
the benefit of occlusion of the aneurysm neck while
maintaining distal perfusion [2]. Although an ele-
gant solution, the anatomy must be such that there
is enough of a landing zone proximal and distal to
obtain an effective seal on both ends of the graft to
exclude the aneurysm. Further device development
and experience are needed to perfect this therapy.
Embolization of Visceral Arterial Aneurysms
If the aneurysm is amenable to direct percutane-
ous puncture, another opt ion includes direct throm-
bin injection or coiling via an 18-gauge needle.
Simultaneous balloon occlusion of the aneurysm
neck via arterial access can be performed to prevent
nontarget embolization.
twice as often as females, and patients are typically
in their fifties. Hepatobiliary and intraperitoneal
rupture occur with equal propensity. These lesions
tend to be solitary although they can be multiple
in conditions such as polyarteritis nodosa [4,12].
Multiplicity is also seen with amphetamine abuse
and trauma.
8.6.2
Causes
8.6.1
Incidence
Hepatic artery aneurysms comprise 20% of all
visceral aneurysms [4, 10-12]. Eighty percent are
extrahepatic and 20% are intrahepatic. The majority
affect the common hepatic artery. Males are affected
Mycotic aneurysms from bacterial endocarditis were
initially the most common cause of hepatic artery
aneurysm [11]. However, traumatic and iatrogenic
causes are likely the most common etiology today.
Medial degeneration and atherosclerotic changes
have also been implicated. However, atherosclerosis
is more likely the result rather than the cause of the
First and Second Line Tools for Emblization
Celiac (Splenic, Hepatic, GDA, Pancreaticoduodenal):
• First choice:
- 6 F sheath in common femoral artery
- 5 F Sos to engage the celiac artery
- 3 F microcatheie: :::d pidewire coaxially
- microcoils apo:op:ia;i:ly size.". [.:■ til tlie :a:gel he.'a;ic
• Second choice:
- 5 F Sos to select the celiac
- exchange groin shea;h to: .'- Rahsin sheath or guiding
catheter to maintain access re the celiac artery
- Bentson or hydrophilic wire to gain peripheral access
using a 5 F Cobra calhele: io.ni be 4 F hydrophilic)
- Coaxial use of .'. microcatheter or cirecl embolization
through Cobra
SMA
• First choice:
- 6 F sheath in common femoral artery
- 5 F Sos to engage the superior mesenteric artery
- 3 F microcaiheie: a:'.d piidewire coaxially
- microcoils approp: lately sized ;o fit the target
• Second choice:
- 5 F sheath in the left brachial artery
- 5 F MPA to engage the SMA
- 3 F microcaiheie: a:'.d piidewire coaxially
- microcoils approp: lately sized ;o fit the target
IMA
• First choice:
- S F sheath
- 5 F RIM catheter
- 3 F microcaiheie: and p::deu : ire coaxially
- microcoils appropi ;ilr'v sized ;o fit the target
• Second choice:
- 5 F sheath :n the let; orach ial artery
- 5 F MPA or vertebral artery catheter (for the length)
to engage the IMA
- 3 F microcaiheie: and pi:deu : ire coaxially
- microcoils appropi ;,\w',y sized ;o fit the target
Renal
• First choice:
- 6 F sheath in common It:" oral artery
- 5 F Sos to engage the renal artery
- 3 F microcaiheie: and pi;deu : ire coaxially
- microcoils appropriately si/.ed to :';l ;lie iarget renal
• Second choice:
- 5 F Cobra to select the renal artery
- exchange groin shealh foi a Balk j:: sheath or guiding
catheter to maintain access lo die renal artery over a
- obtain peripher.il access with iheSFCobra
(can be 4F hydrophilic)
- Coaxial use of a microcaiheier or direct embolization
through Cobra
• Other options:
- 500-700 or 700-900 micron
PVA/embo spheres/Contour SE in vascular beds wltli
good collateral flow
- Stent-graft where amv.emy is favorable
- Direct puncture with an 1 S-g needle foi coil, thrombin,
or glue injection
lan and M. D. Darcy
aneurysm. Inflammatory processes and vasculitis
also cause hepatic artery aneurysms. Polyarteritis
nodosa, systemic lupus erythematosus, Takayasu's
arteritis, and Wegener's granulomatosis have all been
implicated in published case reports [11-13]. Congen-
ital arteriopathies such as Marfan syndrome, Ehlers-
Danlos syndrome, and hereditary hemorrhagic telan-
giectasia can lead to aneurysm formation [14].
8.6.3
Risks Posed by the Aneurysm
ent with
melena,
present:
Intrahepatic rupture can result in hemobili
without biliary obstruction. These patients can pres-
ight upper quadrant pain, jaundice, fever,
hematemesis.Extrahepatic rupture usually
:utely and can lead toexsanguinationdueto
itraperitoneal hemorrhage. They can erode
^structures such as the stomach, common
bile duct, duodenum, or portal vein. Due to the high
mortality from rupture, elective treatment of small
asymptomatic aneurysms has been advocated.
8.6.4
Management
iitfoadjai
five angiography is performed. Portal vein patency
should be confirmed prior to occluding any vessel
supplying the hepatic parenchyma. Approach from
the left brachial artery may be required if the celiac
axis cannot be catheterized due to an unfavorable
angle off the aorta. Furthermore, if the origin of the
celiac is occluded, retrograde catheterization of the
GDA can be attempted from the SMA. Hydrophilic
or microcatheters are helpful to navigate tortuos-
ity. Once securely positioned within the origin of
the common or proper hepatic artery, the micro-
catheter can be used to perform selective angiog-
raphy and embolization. Distal to proximal coil
deposition should be performed for small intra-
hepatic aneurysms in peripheral vessels. In cases
of multiple traumatic pseudoaneurysms, Gelfoam
embolization can be used to temporarily tampon-
ade bleeding.
Treatment of saccular aneurysms that arise from
the common, proper, or extrahepatic right and left
hepatic arteries require more planning. Selective
coil or percutaneous thrombin injection are options
that can allow for continued perfusion distal to the
aneurysm. Tortuosity and small caliber may pre-
clude stent graft placement. The GDA can be sacri-
ficed if absolutely necessary due to collateral flow
from the SMA.
8.6.4.1
Anatomic/Physiologic Con:
The liver
i "dual" blood supply fromboth the
■s and the portal vein. Although good
collateral flow exists, necrosis can occur if enough
arterial supply is occluded at the time of emboliza-
tion. Therefore, it is wise to assess the direction of
blood flow in the portal vein because hepatofugal
flow may increase the risk of infarction. One should
be cautious and superselective when embolizing in
the presence of portal vein thrombosis.
There have been reports of recanalization of
pseudoaneurysms after percutaneous embolization.
Follow-up ultrasound, CT, or MRI can be performed
to assess success of embolization [4,15]. One must be
aware of the relatively frequent anatomic variation
seen in the hepatic artery distribution.
8.6.4.3
Results of Embolization
Review of the relatively limited literature reveals
that embolization with coils, Gelfoam, detachable
balloons, or glue and placement of stent grafts
is technically successful in 95%-100% of cases
[6,10,16-22]. Failures were typically d
when patients tended to rebleed. In
follow-up imaging was performed, a s
were found to recanalize [19,22]. In s
recanalization, success] ul thrombosis
percutaneously with glue using the co
in the series by Parildar et al. [22].
8.6.4.4
Complications
i early
8.6.4.2
Techniqui
:ally, the celia
■r Cobra cathet
axis is selected with
■from the groin and n
Complications of the embolization procedure
include those of diagnostic angiography with the
addition of aneurysm rupture, nontarget emboli-
zation, ischemia or infarction, abscess formation,
and rarely sepsis. In earlier literature, spontaneous
Embolization of Vis!
rupture occurred in as many as 44% of cases [23].
It is likely that this rate is much lower today due
to earlier discovery with frequent and improved
imaging. However, mortality associated with rup-
ture is still nearly 35% [24]. Although small case
numbers, rupture during manipulation has not been
reported in the current literature [25-27]. In 1986,
Uflacker reported successful treatment of 11 cases
of visceral artery aneurysms by coiling feeding ves-
sels both dista]]y and proximally, thus reducing the
risk of rupturing the fragile pseudoaneurysm wall
by directly coiling the sac [28].
8.7.1
Incidence
8.7.3
Management
8.7.3.1
Anatomic/Physiologic Considerations
The splenic artery arises from the celiac axis and
is often tortuous. Therefore, glide wires and hydro-
philic catheters are helpful in gaining peripheral
access to this vessel. It has a long course from the
aorta to the splenic hilum, making it one of the most
amenable arteries for stent graft placement. It sup-
plies branches to the body and tail of the par
If necessary, complete occlusion of the main sple
artery distal and proximal to the aneurysm m
canbe performed. If the artery is completely thro
bosed, collaterals can be parasitized resulting i
splenic remnant or even hypertrophy of splenu
after an embolization.
Considered the most common, the splenic artery
aneurysm has been reported to comprise approx-
imately 60% of all VAAs [1,2]. This entity affects
females four times as often as males. Typically seen
in multiparous women, this aneurysm has a high
propensity to rupture in the third trimester of preg-
nancy [29]. Asymptomatic aneurysms can often be
seen as round calcified masses in the left upper quad-
rant on plain films and computed tomography. This
type of aneurysm has been associated with portal
hypertension. Many causes exist and include pan-
creatitis, portal hypertension, endocarditis, cystic
medial necrosis, iatrogenic, and collagen vascular
diseases such as Ehlers-Danlos.
8.7.2
Risks Posed by the Aneurysm
Life-threatening rupture, which commonly occurs
in the third trimester of pregnancy, is a serious risk
of splenic aneurysms. The small 2-3 cm asymp-
tomatic lesions typically pose no immediate threat
and can be observed with serial CT. There is some
debate regarding the size of aneurysm that can be
observed. However, patients who develop left upper
quadrant or abdominal pain with no other identifi-
able source would likely benefit from elective embo-
lization even if in the 2-3 cm range. Although not
defined, rapid interval growth should also be an
impetus to embolize because the morbidity from
rupture is significant.
8.7.3.2
Technique
Typically a groin approach is used and the celiac
axis is selected with a Sos catheter. Selective angi-
ography is performed to lay out the splenic artery.
A glidewire is then passed distally and either the
Sos or a Cobra catheter is advanced. Embolization
can be performed through the 5 French catheter at
this point. If too tortuous, then a microcatheter can
be passed coaxially. (Fig. 8.4) We use either a Mass
Transit® (Cordis, Miami, FL) or Renegade® (Boston
Scientific, Boston, MA) microcatheter. These cath-
eters can withstand a power injection of 2-3 cc per
second if needed.
Coil embolization is technically easy and suc-
cessful. Coils should be sized slightly larger than the
vessel lumen. Smaller coils or Gelfoam can be used
to sandwich or "nest" between the flanking coils.
This will ensure a compact and occlusive embolus.
Patients should be observed for splenic infarction,
although short gastric or other small collateral ves-
sels can perfuse portions of the spleen distal to the
occluded main renal artery.
A long guiding catheter can be used to secure
access or to upsize from the standard 6F short
sheath used in the common femoral artery, should a
stent graft be chosen. The splenic artery is probably
the most amenable to stent graft insertion due to its
long length and relative lack of branch vessels feed-
ing other organs. Although tortuous, the vessel will
often straighten out when a wire is passed distally.
n and M. D. Darcy
r "i
Fig.8.4. a Nonselective cej.ic imgiogiam m a patient with a large
splenic pseud oaneurvsiv. ■liter trauma. Noie the marked vasospasm
and contrast pooling i:i the lei'i upper quadrant, h Coaxial use of a
micro catheter to obtain access distal to the neck of the pseud oan-
eurysm despite the vasospasm, c h\ I ;::»-■ :p splenic angiogram after
coil embolization of the splenic artery. No further contrast extrava-
sation was noted and the patient's vitals stabilized. (Courtesy of
James R.Duncan, MD)
A good landing zone of at least 1 to 2 cm is required
on either side of the aneurysm neck to obtain a
seal. Self- expanding stent grafts such as the Via-
bahn (Gore Inc., Flagstaff, AZ) are readily available,
but are far too large for use in the visceral vessels.
Smaller coronary stent grafts such as the balloon
mounted Jostent'- 1 (Ahoott L;.i hoi-atones. Inc., Abbott
Park, Illinois) have been used, but are not readily
available or approved for this indication. Although
delivery is more precise, balloon-mounted stents
are less flexible. Flexibility is desirable for passing
catheters through tortuous vessels. Currently, there
is little published on stent graft use for VAAs, and
more investigation i:
8.7.3.2
Results of Embolizatioi
TV. Iin
cess is high, approaching 100%. On the
that the celiac axis is occluded or too
stenotic, access to the splenic artery can be obtained
by retrograde cannulation of the gastroduodenal
artery from the SMA. The GDA is often hypertro-
phied if the celiac has been chronically occluded. In
this case, getting coils through multiple turns may
not be possible. However, if the catheter tip is in a
secure enough position, particles such as PVA or a
Gelfoam slurry can be used to stop acute bleeding
prior to taking the patient to the operating room.
Embolization of Visceral Arterial Aneurysms
8.7.3.3
Complications
Complications of the embolization procedure
include those of diagnostic angiography" with the
addition of aneurysm rupture, nontarget emboli-
zation, splenic infarction, abscess formation, and
rarely sepsis (Fig. 8.5}. Total splenic infarction can
occur, which puts the patient at an increased risk
of infection with encapsulated bacteria such as
pneumococcus. Older literature suggests that bland
splenic artery aneurysms rupture at a rate of approx-
imately 2% [30]. However, in pregnant patients, rup-
ture occurs in nearly every case with mortality rates
for mother and fetus 70% and 95% respectively [31].
Obviously, any aneurysm in the pregnant female
should be addressed since over 95% will rupture if
left untreated [30,32].
After a retrospective review of ten years of expe-
rience, Carr et al. found that 42% of their cases of
VAAs presented with rupture [33]. Half of all the
VAAs were splenic .irtery aneurysms. Of the splenic
artery aneurysms that were observed, 33% went on
to rupture. This is much higher than the previously
reported 2% rupture rate and reflects the fact that
the patients in the series by Carr et al. suffered
from associated conditions such as hypersplenism,
pancreatitis, abscess, and PAN. The overall mor-
tality rate after rupture was 25% despite surgical
intervention [33]. This would suggest that interven-
tion should be pursued in cases due to associated
conditions since a high rupture rate exists during
observation. Incidental aneurysms can be watched.
Again, no case reports of rupture during manipula-
tion were encountered in the current literature.
Incidence
The superior mesenteric artery aneurysm is the third
most common VAA but only accounts for 6% of all
splanchnic aneurysms. It is typically associated with
an infectious etiology such as endocarditis. Throm-
bosis and dissection can be seen with these lesions
and patients can present with symptoms of mesen-
patienl fro::: !-':gure 4 ..". c ["!'.■."■ i"i ^ I :",i i -
i:'.g ,i perisplenic abscess. The pa tic::: J eve loped fever and an
elevated white cell count one week after embolization. Note
arterial perfusion c:' a sp>::ic remnant medial to the abscess.
b iIT image inferior to that o:' a demonstrating the coils n.
the splenic hilum. Collateral Sow to the spleen despite com-
plete occlusion of the splenic a: tery exisis. t Inferior aspect
of I he abscess distinguishing kitinev from the residual spleen,
i Courtesy of Jaines R. Duncan, MP i
n and M. D. Darcy
teric ischemia or intestinal angina. Aneurysms and
pseudoaneurysms of the remaining mesenteric ves-
sels are rare and present in descending frequency:
celiac, gastroduodenal (GDA) (Fig. 8.6}, gastric,
gastroepiploic, and pancreaticoduodenal. There is
no significant gender predilection for mesenteric
aneurysms, and the age range typically spans the
sixth and seventh decades.
Fig. 8.6. a Nonselective angiogram of the celiac axis, o'emonslraiing
a pseudoiinenrysm of the l.F'A. b I'eiayed image ih.il shows persis-
ieni coairast willun the pseudoLineurysm sac. t Follow-up subtracted
image alhei coil cmooj'zaiion wi;h a niicroca;he : .er. No furthet hhing
of the pser.doaneuiysni from ihe GHA is noted, d selective nonsub-
tiacteti injection of a duodenal branch ciemonslrates rodateinl tilling
of :he pseud OL\neu:ysm thai would lead to fr.r.hci henioi ih.ige. e Final
subtracted .mage alter embolization oi ihe col.a;eral vesse! with PVA.
Thrombosis of the feeding vvssels has been achieved
Embolization of Visceral Arterial Aneurysms
8.8.2
Causes
Generally, SMA aneurysms are mycotic, celiac
aneurysms develop from cystic medial degenera-
tion, GDA pseudoaneurysms occur in the presence
of duodenal ulceration, and gastroepiploic and
pancreaticoduodenal aneurysms arise secondary
to inflammatory changes from pancreatitis. Other
causes include polyarteritis nodosa, amphi
abuse, and connective tissue disorders.
8.8.3
Risks Posed by the Aneurysm
Ischemia from proximal thrombosis c
lization and rupture are significant i
these types of VAAs. Local infectic
hematomas and generalized sepsis c;
sequent bowel resection maybe requii
from thrombosis or embolization is si
cularization is not possible.
distal embo
1 of adjacent
i occur. Sub-
id if ischemia
8.8.4
Management
8.8.4.1
Anatomic/Physiologic Considerations
Due to good collateral flow, complete occlusion of
splenic, peripheral hepatic, and gastroduodenal
arteries is well tolerated. Ischemia, stricture, and
infarction of the bowel can result from emboliza-
tion in the peripheral SMA and IMA distributions.
Because of the rich arcade around the pancreatic
head, the GDA can easily reconstitute the celiac axis
via retrograde flow from the SMA. This is beneficial
for preventing ischemia, but can allow persistent
perfusion of aneurysms if both distal and proximal
control is not achieved at the time of embolization.
Often, pseudoaneurysm formation in the pancre-
aticoduodenal, SMA, and IMA distributions is due
to adjacent inflammatory processes such as pan-
creatitis or diverticulitis. (Fig. 8.7) Hematomas in
the mesentery can become abscesses. Even though
microcoils are used in these instances, it is unwise to
implant a stent graft into a potentially infected bed.
8.8.4.2
Technique
Technique will vary significantly depending on the
vascular distribution of the mesenteric aneurysm.
Typically, celiac and proximal SMA aneurysms are
best treated surgically.
Although a common femoral approach is prefera-
ble to that of the brachial artery, a lelt upper extrem-
ity puncture may be required to negotiate the acute
angles the visceral arteries take from the aorta. A
Sos catheter works well from the groin, and an MPA
is typically all one needs from the arm. Guiding
catheters or sheaths offer support and directional-
ity if access is difficult to maintain.
Fig. 8.7. .i -r,::ivr .m ■;.■■.■>-" '' mi .i-r\v.- c--i.::v.\::c .■ p;iriido:i:":ei:rv>:v. of [.;; ■= i g m ■.:■■: o Lv:i;:cli of I lie !M.A dr.e k- -^ :vej : i .r , I i i i i - : . h :'ol«-
'.::'' siibt:;icled .ii:.itie driiio:^ I idling cod occlusion o: both Lin; itches tli.ii were siipplv.iio. die ..cue psendo.ii'.eiirv-i-ii. No- isch.e:r.::]
resulted due to coll.'.ter.i. rkuv from inter n.d ijjc LT.'.ndies vi.i I lie heniorrhoid.il .rrteries. (Courtesy of lean iter E. Gould, MD]
lan and M. D. Darcy
As long as there is no celiac, proper hepatic, or
SMA origin occlusion, the GDA can be sacrificed.
If the GDA is required to maintain perfusion of the
liver or, if flow into the S.MA is dependent upon the
celiac, then direct coiling of GDA pseudoaneurysms
is preferable. This can be accomplished with stent
placement over the aneurysm neck and microcoil
deposition through the interstices via a microcathe-
ter. A small-caliber stent graft such as a fostent could
theoretically be used in this situation. However, use
of this device is still not approved by the FDA. Appel
et al. described the placement of a 26-mm stent graft
for humanitarian treatment of ;i trail ma tic pseud oa-
neurysm of the SMA [34].
The RIM catheter was specifically designed for
the inferior mesenteric artery. This catheter typi-
cally seats well in the origin, which arises at the
level of the left pedicle of L3. A microcatheter can
then be passed coaxially into the desired branch
and microcoils deposited. Supers elective technique
is desired. Although some collateral flow is supplied
to the distal colon via internal iliac branches, care
must be taken when occluding more proximal vas-
cular territories.
8.8.4.3
Results of Embolization
Results of transcatheter embolization of mesenteric
aneurysms appear favorable in the literature, and
technical success has been reported to range from
75% to 100% [1,3,15,18,19,24-27,33,35-42]. However,
many of these studies are not only retrospective and
small, but the mesenteric VAAs are often lumped in
with splenic and hepatic artery aneurysms, making
it difficult to isolate effective treatment rates for
SMA, IMA, and GDA aneurysms independently. The
anatomy and location of the lesion will often dic-
tate the success of embolization. Furthermore, some
case series report the use of different methods, such
as percutaneous thrombin or coil injection versus
transcatheter embolization.
thromboembolic phei
manipulation. Smaller emboli not seen during t.
embolization procedure may become evident a fi
hours later and manifest as abdominal pain. Tr
typically resolves with heparinization, pain ma
agement, bowel rest, and time. If hemorrhage occu
in the mesentery, abscesses can develop and perc
taneous drainage may be required.
8.9.1
Incidence
Incidence rates of aneurysm formation differ for
the various etiologies of renal artery aneurysms.
However, the literature suggests that incidence rates
range between 0.015% and 9.7% [43], A classifica-
tion scheme divided into saccular, fusiform, dis-
secting, and pseudoaneurysms has been described
by Poutasse [44,45]. The natural history of these
aneurysms is not well defined in the literature. How-
ever, there are small and large case series that dem-
onstrate low rupture rates ranging from 0% to 14%
[46-50]. Hubert et al. followed some patients with
solitary aneurysms as large as 4.0 cm for as long as
17 years without rupture [50]. Renal artery aneu-
rysms that are treated surgically are approached by
nephrectomy, ex vivo repair, and auto-transplanta-
8.9.2
Causes
Typically pseudoaneurysm formation in the renal
artery distribution Is iatrogenic or traumatic. Other
causes of aneurysm formation include fibromuscu-
lar dysplasia, polyarteritis nodosa, amphet
abuse, angiomyolipoma in the presence or ab:
of tuberous sclerosis, and neurofibromatosis.
8.8.4.4
Complications
The major complicating factor of embolization
in the mesenteric distribution is bowel ischemia
and infarction. Ischemia can cause strictures and
obstruction whereas infarction can lead to perfo-
ration and sepsis from dead gut. Dissection and
Risks Posed by the Aneurysm
Rupture is
pregnant v
with splen
rare risk of these aneurysms. However,
nen are more prone to rupture just as
artery aneurysms. Schorn et al. pro-
ew of the literature regarding the
Embolization of Visceral Arterial Aneurysms
risk of rupture of these lesions [51]. They found one
dated series that described the risk of rupture as high
as 14%. However, many subsequent large autopsy
series demonstrated no instances of rupture when
renal artery aneurysms were present. In their review
of the literature, they also discovered that noncalci-
fied aneurysms were more at risk of rupture.
In cases of FMD, distal embolization and dissec-
tion can be seen. Malignant hypertension may be
the presenting symptom as a result of embolization
of clot from the aneurysm or occlusion from a dis-
section flap.
8.9.4
Management
8.9.4.1
Anatomic/Physiologic Considerations
The vascular supply to the kidney is considered end-
organ, and infarction is common after emboliza-
tion. Therefore, in patients with renal insufficiency
or underlying diseases such as tuberous sclerosis
or von Recklinghausen's disease, nephron-sparing
procedures are vital. Superselective embolization is
advisable in all cases of renal artery embolization
unless partial or total nephrectomy is planned.
8.9.4.2
Technique
The renal arteries arise at the L2 level from the
abdominal aorta. A 10° LAO view during a flush
injection of the aorta will often provide the best
view of the origins. Careful examination for acces-
sory renal arteries is necessary. A Sos or Cobra
catheter will easily select the main renal ostium. A
Rosen wire is an atraumatic guidewire that allows
for secure exchange or upsizing to a guiding cath-
eter or Ealkin sheath. Selective injection should be
performed to identify the feeding vessel or vessels.
This can be done through the sheath.
Many embolization techniques can be used in
this setting depending on the type, number, and
location of the aneurysms. For example, aneurysms
of the main renal artery may be amenable to stent
graft placement, thus allowing distal perfusion to
be maintained [52-56]. However, until stent graft
placement is perfected, surgical repair by resection,
aneurysmorraphy, ;ind aulotrfmsphntation is more
inly performed in this setting.
More peripheral aneurysms can be selectively coil
embolized using microcatheter techniques. Both
distal and proximal control is not always possible,
and may not be necessary due to the vascular anat-
omy. In the presence of multiple aneurysms from a
lesion such as an angiomyolipoma, a combination
of particle and coil embolization can be performed.
If actively bleeding, the aneurysms are coiled first,
followed by occlusion of the feeding vessels to the
tumor with PVA or embospheres. Gelfoam can be
sandwiched between coil nests to assist thrombo-
[( surgica] resection is planned, ablation of entire
lobar or main renal arteries can be performed with
ethanol. This requires the use of a balloon occlusion
catheter such as a single lumen Balloon Wedge-Pres-
sure Catheter (Arrow International, Reading, PA) to
prevent systemic spread of alcohol. Ethanol ablation
should be performed within one or two days of the
planned resection. This will help to avoid a pro-
longed post-embolization syndrome, which can be
quite uncomfortable for patients and can reduce the
risk of abscess formation from the ensuing infarc-
8.9.4.3
Results of Embolization
The technical success is quite high once the renal
artery is securely accessed. If superselective tech-
niques are used, very little ischemia results and
there is very little chance of inducing renal failure.
The small number of reported cases in the literature
makes it difficult to assess the long-term s
tiansauheter embolization.
8.9.4.4
Complications
Although rare, dissection or perforation of the renal
arteries and their branches can occur. Rupture may
lead to rapid development of retroperitoneal hem-
orrhage. Both dissection flaps and rupture can be
immediately controlled with balloon tamponade.
Although dissection flaps can often be tacked down,
rupture typically requires emergent surgery. Even
perforation of smaller branch vessels can occur if
a guidewire is passed too far into the periphery.
Hematoma and abscess can develop.
Embolization of plaque from heavily calci-
fied arteries or aorta is a risk when manipulating
lan and M. D. Darcy
sheaths or catheters in the origins of these vessels.
Even though richly vascular, the renal parenchyma
is prone to ischemia and infarction due Co its end-
organ supply. Every attempt should be made to
become as selective as possible Co preserve distal
flow and prevent nontargeC embolization.
Care must be Caken when embolizing wich abso-
lute eChanoldue Co the vigorous thrombosis it causes
by denaturing proteins. Echanol can cause seizures
and inCoxication if ic reaches Che systemic circula-
tion. It can also permeaCe Che tissues and cause injury
lo ad i .ice nt structures such as bowel and nerves.
Complications
Access site complications include hematoma, pseu-
doaneurysm formation, and arterial dissection.
Although sometimes unavoidable, good technique
should keep these complications at an acceptable
level. Brachial punctures are slightly more prone to
complicaCion, especially neural compression from
hemaComa. Ic should also be remembered ChaC work-
ing from the left arm entails a catheCer crossing Che
origin of Che left verCebral artery, and a sheath will
be nearly occlusive in the brachial arCery. If pos-
sible, using a smaller sheath such as a 4 or 5 French
system can help diminish post-procedure complica-
tions. Microcatheters will work coaxially through
4 French caCheters.
Placement ol a vascular sheath serves two impor-
tant purposes. It protects the access artery from
injury if multiple catheter exchanges occur, and it
maintains access to Che arCery should the working
catheter become occluded.
Aneurysm rupture during vigorous contrast
mieifion or direct manipulation can occur. Emer-
gent tamponade can be achieved by inflating a bal-
loon either across the neck of Che aneurysm or in the
origin of the feeding vessel. Having an appropriately
sized balloon occlusion catheCer ready on Che back
table can be useful should rupture occur during the
procedure. Emergent surgery may be necessary if
the bleeding cannoC be controlled or if permanent
embolization of the parent vessel is not technically
feasible. The ruptured aneurysm may continue to
bleed if distal occlusion is not achieved.
One of the feared complications of deploying
coils, injecCing Chrombin or glue, or infusing par-
ticulaCe embolics is nontarget embolization. SCrin-
genC Cechnique Co ensure satisfactory positioning
of catheters is vital to prevent nonCarget emboliza-
Cion. Before embolizing, catheCer stability should
be CesCed by passing a wire through it. Catheters are
more apC Co buckle out of vessel origins and cause
nonCargeC embolization or loss of access in the pres-
ence of extremely torCuous courses. Should a coil
become lodged in Che caCheCer, a forceful injecCion
wiCh a 1- or 3-cc syringe can be aCCempCed Co torpedo
it free. However, this maneuver may back the cathe-
Cer out of the CargeC vessel. If nonCargeC embolizaCion
of a coil occurs, a snare can be used in an attempt Co
reCrieve ic if it lodges in an undesirable location.
Sinceminiscule amount soi thrombin are required
Co thrombose aneurysms, great care should be Caken
when injecting this embolic. Distal embolization
during thrombin injection usually resolves without
significant sequelae. Although not always possible
with VAAs, the use of real-time ultrasound can help
Co moniCor Che progress of thrombosis. Obtain-
ing arCerial access provides the ability Co balloon
occlude the origin of the aneurysm when injecting
Che aneurysm percutaneously.
Future Development and Research
Coil embolization has been one of the mainstays
of VAA treatment and has been augmented wich
direct glue or thrombin injection. Coil design has
not changed sigmhauifly. However, extremely pre-
cise deployment mechanisms such as electrolytic
detachment are available today.
Many different agents, both temporary and per-
manent (Gelfoam, glue, thrombin, PVA, detachable
balloons, and eChanol)canbe used depending on the
situation and the desired end result. There has been
no significant change ot these materials in the las!
fewyears. Refinement of PVA into embolic "spheres"
has been achieved, and is thought to provide a more
uniform embolization rather than the clumping that
can occur with regular PVA. A newer nonadhesive
liquid embolic agent called Onyx (Micro Therapeu-
tics. Inc., Irvine, CA) has been used in some neu-
roinCervenCional and neurosurgery applications.
Because Onyx is nonadhesive, care must be taken
when using this product dueCoChepropensiCy of the
embolic to migrate into Che parenC vessel.
The fuCure may lie wiCh sCenC graft placement,
which has been performed with good Cechnical suc-
cess inChelasC four years, albeit in small case reporCs
[16, 34, 52, 54-67]. However, no long-Cerm daCa exisC,
Embolization of Visceral Arterial Aneurysms
and further investigation is warranted. The capacity
to occlude aneurysm necks while maintaining distal
perfusion in a single step would seem to make stent
grafts the ideal therapy. However, small vessel diam-
eter, short landing zones, frequent bifurcations, and
tortuosity provide ample hurdles for placement of
stent grafts in the visceral arteries. Furthermore,
the paucity of these cases makes it difficult to collect
statistically significant data and gain experience in a
short period of time. Therefore, there is little to drive
the market to further develop this technology.
8.12
Conclusion
Although quite rare, visceral artery aneurysms are
life-threatening when hemorrhage occurs. Aggres-
sive management by the interventional radiologist
is paramount. Often, these patients are too sick for
major revascularization procedures, making endo-
vascular techniques a more desirable approach. Sur-
gical morbidity and mortality is fairly high after
aneurysm rupture.
The asymptomatic lesions are being discovered
more regularly due to the increased demand for
crow-sectional imaging. The timing ol treatment
depends onaneurysm size and location. For example,
some authors have suggested treating asymptomatic
splenic artery aneurysms while others have argued
that observation is adequate [60, 68, 69]. However
observation is the exception rather than the rule
with visceral artery aneurysms. All splenic artery
aneurysms in women of child-bearing age should be
treated due to the high incidence of rupture in the
third trimester. All mesenteric aneurysms should
be treated due to a high likelihood of complications
from rupture, thrombosis, or embolization.
A variety of methods for embolization of VAAs
are described in the literature. The type of treat-
ment should be tailored to each individual case as
the anatomy will typically dictate the therapy best
suited.
Despite the fact that minimally invasive embo-
lization procedures have been performed for over
twenty years, very few long-term data on VAA
occlusion are available. Further investigation and
development of newer techniques such as stent graft
placement are needed. Coil, glue, thrombin, and
particle embolization will continue to be effective
methods for treatment ot visceral artery aneurysms
in both the elective and emergent settings. Good
technique and a firm understanding of the visceral
vascular supply are vital, just as in any embolization
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;nt-graft.AJR
artery Car-
Venous Ablation
Endovenous Thermal Ablation of Incompetent
Truncal Veins in Patients with Superficial Venous
Insufficiency
Neil M. Khii
[iilToduotion 119
Pathophysiology mid Epidemiology 119
Anatomy 119
EVTA: Background 120
Evaluation Prior to EVTA 121
EVTA Technique 121
Clinical Data 12 3
Summary 125
References 125
Introduction
Endovenous thermal ablation has become an
accepted option to eliminate the reflux caused by
incompetent saphenous veins. In this chapter, a
review of the clinical problems and anatomy pre-
cedes a review of this exciting new venous occlusion
technique.
Pathophysiology and Epidemiology
of patients with all forms of CV1 have significant
superficial venous insufficiency (SVI}. If present,
treatment of CVI begins with elimination of this
reflux. Reflux in the saphenous (truncal) veins is the
most common cause of venous hypertension. Patho-
physiologically significant reflux in the great saphe-
nous vein (GSV) or in one of its primary tributaries
is present in 70%-80% of patients with CVI. Small
saphenous vein (SSV) reflux is found in 10%-20%
and non-saphenous superficial reflux is identified
in 10%-15% of patients [2, 3].
SVI is certainly the most prevalent medical con-
dition treated by interventional radiologists. Up
to 25% of women and 10% of men in the U.S. are
affected, with 50% of people >50 years old having
some form of SVI [3]. Most patients with SVI have
symptoms, which include aching, fatigue, throb-
bing, heaviness, and night cramps. A minority of
patients develop skin injury from chronic venous
hypertension, which includes eczema, edema, pig-
mentation, lipodermatosclerosis, and ulceration.
Heredity is the primary risk factor for developing
SVI; 85% of patients are affected if both parents are
involved, 47% if one parent is involved, and 20% if
neither parent is involved [4]. Prolonged standing
and multiparity increase the risk of expressing this
heritable risk.
Lower-extremity chronic venous insufficiency (CVI)
is caused by venous hypertension [1]. Most patients 9.3
develop venous hypertension from the hydrostatic Anatomy
forces produced by reflux that results from primary
valvular insufficiency [2] Venous obstruction, mus-
cular pump failure, and congenital anomalies are
much less common causes. In addition, 85%-90%
N. M. Khilnani, MD; R. J. Mln, MD
Cornel! Vasail-ar. Weill Median! College of Cornell Uiiiversiiy,
416 East 55th Street, New York, NY 10022, USA
The superficial ven<
ties is composed of inn
lecting veins, the saphe
taries. The GSV begins
portion of the foot, run
leolus, and ascends the
thigh to ultimately join the femoral
le (saphe note moral junction, SFJ)
system of the lower extremi-
lumerable subcutaneous col-
nous trunks and their tribu-
; on the anterior and medial
s anterior to the med ial mal-
aspect of the calf and
at the fossa
meters below the inguinal ligament (Fig. 9.1). The
GSV is adjacent to the saphenous nerve (sensory)
N.M.Khilnani and R.J.Min
Fig.9.1. Frontal and posterior diagrams
of the lower extremi-y demonslriuing
the great and small saphenous veins and
their named tributaries. The two saphe-
nous systems can be connected via the
vein of Giacomini
from about 6 cm below the knee to the ankle. The
GSV and its major named branches run superficial
to the deep and deep to the superficial fascia within
the saphenous space. The GSV has two important
and named tributaries above and below the knee:
the anterior and posterior circumflex veins of the
calf and thigh. In addition there are three smaller
tributaries at the groin which are important in that
they are often a source of recurrent varicose veins
following their surgical ligation along with the GSV
(high ligation). A common variant, the anterior
accessory GSV (AAGSV), runs more laterally than
the GSV within the saphenous space and often is
usly termed a duplication of this trunk. This
s frequently present and can be responsible for
>n the anterior aspect of the thigh.
An extrafascial tributary vein that communicates
with the GSV but runs parallel to the GSV course
and is relatively straight should be described as a
superficial accessory GSV.
The SSV begins on the lateral aspect of the foot,
ascends posterior to the lateral malleolus and then
up the midline of the calf, between the same fascial
is the GSV. The SSV runs adjacent to the
rve (sensory) from just below the popliteal
crease to the foot. In about two thirds of cases, the
SSV drains into the popliteal vein at or just above
the popliteal crease. In about one third of cases it
has a cephalad extension with or without a saphe-
nopopliteal junction (SPJ) to ultimately drain into
planes
a posterior thigh perforating vein, ot
terior circumflex vein of the thigh v
Giacomini (Fig. 9.1).
EVTA: Background
Treatment of SVI is indicated for symptoms unre-
lieved by conservative methods such as graduated
compression stockings (GCS), exercise, and avoid-
ing prolonged standing. It is also indicated for com-
plications from chronic venous hypertension such
as bleeding varices, superficial thrombophlebitis,
and skin injury. Treatment begins with elimina-
tion of any truncal incompetence. The treatment
modalities available to accomplish this include high
ligation, truncal vein stripping along with a high
ligation, endovenous thermal ablation (EVTA), and
duplex ultrasound (DUS)-guided sclerotherapv.
In the last 5 years, EVTA has developed into a
successful option for obliterating truncal incom-
petence. Its main advantages over surgery are that
there is no need for anesthesia or sedation and no
recovery or down time following the procedure. The
underlying mechanism of this procedure is to endo-
vascularly deliver sufficient thermal energy to the
wall of an incompetent vein segment to produce irre-
versible occlusion. The first modern report of EVTA
Endogenous Thermo] .-VlM.iiion .:■!" [iKcmpeiea/ 7nin.ro! Veins :n f';'.l ient:; wjrli y.-.-.'crn.-j.;l Venous Insufficiency
was made using laser-delivered energy to ablate the
saphenofemoral junction [6]. Since that time several
devices have been approved by the U.S. Food and
Drug Administration. The currently available tools
utilize radiofrequency or laser energy of a variety of
different wavelengths to deliver the required ther-
mal dose.
As mentioned, the goal of EVTA is to endove-
nously deliver sufficient thermal energy to the wall
of an incompetent vein to irreversibly occlude it. A
catheter inserted into the venous system either by
percutaneous access or by open venotomy delivers
the thermal energy. The procedure canbe performed
on an ambulatory basis with local anesthetic and
generally require little or no sedation. The patients
■ally fully ambulatory following treatment
cose tributary and reticular
is are treated separate!)' with
such as compression sclero-
and the
The :
veins and telangiectasi
adjunctive therapi
therapy or microphlebectomy. Some physicians will
perform microphlebectomy for varicose veins at
the same time as EVTA. Other physicians elect to
perform phlebectomy or compression sclerotherapy
of the varicose veins at a later time. Almost all phy-
sicians will defer therapy of spider veins to a later
In our practice, phlebectomy is generally recom-
mended at the same time as EVTA when varicose
tributaries are larger than 8-10 mm in diameter or
when EVTA will occlude their inflow and outflow.
If such veins are left untreated they may thrombose
in 596-1096 of cases and become painful, erythem-
atous, and possibly result in skin pigmentation.
Also, if they thrombose, their complete eradication
may be made more difficult and certainly will be
delayed. For smaller varicose veins and all reticular
and spider veins, we offer compression sclerother-
apy beginning 4 weeks after EVTA. By this point
the veins have substantially decompressed, making
their eradication with injections easier.
9.5
Evaluation Prior to EVTA
Treatment for patients with CVI begins with a care-
ful history and directed physical exam. All patients
with visible varicose veins or symptoms suggesting
venous insufficiency should be evaluated with DUS
[7, 8]. In patients with spider veins near the medial
ankle (corona phlebectasia) or along the medial
calf or thigh, a DUS of the GSV is recommended
to identify truncal reflux. The goal of the DUS is to
determine which veins are normal and which veins
are incompetent to create a map of the pathways of
reflux in a given patient. Such a map is necessary to
define the best combination of treatments which are
available. In some cases, it may be possible to iden-
tify the abnormal vein segments by physical exam.
However, the different pathways of incompetence
overlap sufficiently such that reliance on physical
examination alone will lead to frequent diagnostic
Reflux in truncal veins must be treated prior to
addressing any visible abnormalities. EVTA is a
treatment option for endovenously eliminating such
reflux. The indications for ablation of incompetent
truncal veins are identical to those for surgical liga-
tion and stripping. Absolute contraindications have
yet to be identified for the laser procedure. For RF
ablation, a pacemaker or implantable defibrillator
is ;.i contraindication. Relative contraindications lor
EVTA include absent pedal pulses limiting GCS use,
liver abnormalities limiting local anesthesia use,
pregnancy, nursing, and uncorrectable coagulopa-
thies.
EVTA Technique
Once the pathways of incompetence are established,
EVTA can be utilised to ireat incompetent truncal
veins and straight segments of their tributary veins.
In almost all cases venous access is directly into the
vein to be treated or directly into one of its principle
tributaries, if the tributary vein is straight. Gener-
ally the access is at or just below the lowest level of
reflux in the treated truncal vein as defined by DUS.
This is generally recognized as the level where the
diameter of the truncal vein decreases just periph-
eral to a large incompetent tributary. In many cases,
segmental great saphenous vein incompetence can
occur in two separate portions of this vein. The
reflux can completely spill out into a tributary vein
only to re-enter the GSV at a lower level. It is impor-
tant to determine if the intervening portion of the
GSV is hypoplastic or normal. Hypoplastic segments
occur commonly [9] and cannot be traversed by a
guidewire. In this circumstance, venous access will
be required into the most peripheral part of both
segments and the segments are subsequently ablated
sequentially. Normal intervening segments can be
N.M.Khilmmi and R.J. Min
crossed and allow the operator to treat all incom-
petent segments of the GSV through one venous
Prior to treatment, the treated veins are mapped
and the courses of the treated segments as well as
important landmarks such as junctions, venous
aneurysms and large perforator inflows are drawn
on the patient's skin with a surgical marker. The
patient is then placed horizontal on the table allow-
ing full access to the treated segments. In general,
patients being treated for GSV reflux are placed
supine. Patients being treated for reflux in the SSV
are placed prone with their feet hanging off the end
of the table to relax the calf. Posterior medial tribu-
tary and Giacomini vein ablations may require more
challenging positions.
Venous access is accomplished with either a 19- or
21-G needle using real-time US guidance and a one-
wall technique. The incompetent truncal vein can
become much smaller when the patient lies down.
Placing the patients in the reverse Trendelenburg
position and keeping the procedure room warm can
dilate the vein to make access easier. Also, when
the puncture is directed into a tributary vein or the
AAGSV, care must be taken to avoid venospasm,
which is much more common with missed punc-
tures of these veins.
The details of the laser and RF treatments vary at
this point but the ultimate treatment goals and tech-
niques are similar. With RF ablation, the RF cath-
eter is withdrawn only after its tines are exposed
to allow contact with the vein wall. The catheter is
withdrawn maintaining the vein wall temperature
at or above 85°C as measured by a thermocouple
embedded in its tip. For laser ablation the fiber is
withdrawn at a rate determined by the energy depo-
sition per length of vein treated. For the remainder
of this presentation on technique, the laser proce-
dure will be discussed. The details of the RF venous
ablation can be reviewed in the references cited in
the results section.
For laser EVTA, a 5F sheath is inserted through
the entire abnormal segment and into a more central
vein. A bare tipped laser fiber is inserted to the end
of the sheath, which is then withdrawn exposing the
tip of the fiber. The sheath and fiber are then with-
drawn to place the tip at the staring point of the abla-
tion. For the GSV this is usually about 1 cm below
the SFJ and for the SSV about 2 cm below the SPJ
where the SSV turns parallel to the skin just below
the popliteal fossa (Fig. 9.2). With the laser, confir-
mation of the position can be made with localization
of the light which comes from the red aiming beam
which can almost always be visualized through the
skin.
The most time consuming part of the procedure
is the US-guided delivery of perivenous tumescent
anesthesia (TA). TA is a form of local anesthesia
delivery which was popularized by plastic surgeons
which utilizes large volumes of dilute anesthetic
solutions which are infiltrated to anesthetize large
regions for treatment. TA can make EVTA pain-
less obviating the risks and additional monitoring
associated sedation or anesthesia. In fact, it can be
argued that sedation adds risk to EVTA by blunt-
ing the patients' response to pain making them
potentially more susceptible to extravenous thermal
injury as well as delaying immediate ambulation
after the procedure.
TA is also necessary for safety and efficacy ol
the procedure as well. Large volumes are utilized to
compress the truncal vein to maximize the transfer
of energy to the surrounding vein wall. Even though
venospasm frequently occurs soon after sheath inser-
tion, it is usually still necessary to empty the vein
further with TA to ensure adequate treatment. Also
important is that the large volume of fluid around
the vein is necessary to insulate the vein from the
surrounding structures. This part of the procedure
Fig. 9.2. Longitudinal view of the saphenofemoral junction
(SFJ) during positioning of a Ltser fiber prior to EVTA. The
left of the image is toward the padent's head. A thin arrow
points to the tip pf the laser fi^er approximately 5-10 mm
below die SF[ at die takeoff of the superficial epigastic vein.
The (*) identifies the SFJ, FV the femoral vein, GSV the great
viph.enous ven' ,;:'d J KG t!ir siipcrfkiol epigastric vein
:i of [no;m.peic , ;i: ; run,",il Veins :n Pi'. I ient:; with x^'cinoj.;! VeiiOii; : ji-iiffi.riirii.w
minimizes potential thermal injury to the skin or
adjacent nerves or arteries. In practice a 1-cm-diam-
eter cylinder of TA surrounding the treated vein and
1 cm separation of the treated vein from the skin is
adequate.
For EVTA, we generally use 100-200 ml of a 0.1%
lidocaine solution buffered with sodium bicarbon-
ate. Utilizing these volumes we can get close to the
4.5-mg lidocaine/!;!; dose without epinephrine and
7-mg/kg doses with epinephrine. In plastic surgery
these doses are routinely safely exceeded. The argu-
ment for this safety is that the large volumes of fluid
containing this drug are absorbed slowly avoid-
ing high systemic levels. However, in an outpatient
environment, it is best to avoid reaching these dose
thresholds. In our practice, we also avoid the use
of epinephrine to avoid any toxicity related to this
drug.
After placing the patient in a Trendelenburg posi-
tion to further empty the vein of blood, the sheath
and fiber are withdrawn as a unit through the treated
vein segment as the laser is activated. With DUS, gas
bubbles can be seen to emanate from the tip of the
laser fiber which serves as additional confirmation
of the tip position at the appropriate location.
Suggested parameters vary slightly with the dif-
ferent laser devices but are under the control of the
operator. In our practice, using the 810-nm diode
laser (Diomed, Andover, MA) 14-watt continuous
mode is selected. The amount of energy necessary
to effect reliable vein ablation seems to be an average
of 80 J/cm throughout the treated segment [10]. The
average pullback rate to accomplish this is about
2 mm/s. In practice for the GSV we generally pull
back at 1 mm/s for the first 10 cm or so f treatment
since failures, if they occur, will happen at this loca-
tion. We also pull back at this rate near the inflow
of incompetent perforators or pudendal veins or the
take off of large incompetent tributaries to maximize
successful occlusion at these important locations.
When treating the GSV or a superficial accessory
saphenous vein when the vein is superficial, when
treating the SSVorthe GSV below Boyd's perforator,
we withdraw the fiber at 3 mm/s to minimize skin or
nerve injuries.
Following the procedure, patients should be
placed into a Class II (30-40 mmHg) graduated
compression stocking (GCS) usually for 2 weeks.
The purpose of this is to keep the variceal tributar-
ies as empty as possible in case they occlude to min-
imize the amount of resultant thrombus. The GCS
s the velocity of blood flow in the deep
reasing the likelihood of deep vein throm-
bosis. Anticoagulation with low-molecular-weight
heparins is routinely used after EVTA in Europe but
not in the US.
After EVTA, most patients will develop an ecchy-
mosis over the entire treated segment. This gener-
ally develops the day after the procedure but fades
by about 2-3 weeks. Most patients will comment
about some mild discomfort over the treated vein
which begins hours alter I he procedure but resolves
within 24-48 h. The GCS helps minimize this dis-
comfort; some patients use acetaminophen with
good response. With laser ablation, patients will also
develop a discomfort over the vein about 7-10 days
after the procedure, which is generally described as
being similar to a pulled muscle. This is most likely
caused by transverse and longitudinal retraction of
the vein as the acute inflammation transitions to
cicatrization. This resolves with movement, occa-
sional NSAID use and continued use of the GCS. No
f unlit r treatment has bent n
ryu
Periodic follow-up DUS is suggested to monitor
for the response to therapy. In general, at about 4
weeks following EVTA, one will identify a smaller-
diameter, thick-walled truncal vein likely the result
of significant vein wall injury and its inflammatory
response. Little or no lumen or intraluminal throm-
bus is typically identified and no flow will be found
in the treated segment. By 6-12 months the vein will
continue to shrink in size so that in successfully
treated cases the vein can no longer be visualized
[11-13]. If the vein shrinks to this extent further
follow-up is probably not necessary.
Most patients will require adjunctive treatment of
the branch varicosities. Compression sclerotherapy
and micro-phlebectomy are the most commonly
used techniques to accomplish this. Occasionally,
deeper tributary veins may require DUS-guided
sclerotherapy, and rarely, large variceal clusters will
require conventional phlebectomy.
Clinical Data
The technical success of EVTA is defined as a pro-
cedure with successful access, crossing the segment
to be treated, delivery of tumescent anesthesia and
delivery of thermal energy to the entire incompe-
tent segment. Clinical success is defined as the per-
manent occlusion of the treated vein segments and
successful elimination of re!;
N.M.Khihuni and R.J.Min
an improvement in the clinical classification of the
patients by at least one grade at a certain time inter-
val after the procedure. As previously mentioned,
in practice most patients will also be treated with
either adjunctive micro-phlebectomy or compres-
sion sclerotherapy and as a result the clinical success
data for the different clinical reports can be con-
founded by the success of the adjunctive procedures
and by enthusiasm by which they are utilized by the
treating physician.
Duplex ultrasound is essential to document the
permanent occlusion of truncal veins treated with
EVTA [11-13]. A successful procedure will result in
non- thrombotic circumferential vein wall injury
from the highest level of the incompetent segment
and through its treated course on early evaluation.
On late follow-up the vein segment will ideally be
obliterated and impossible to find or at least will
be significantly smaller in cross section than prior
to treatment and will have no flow throughout the
treated segment.
RF ablation was the first approved device for
EVTA. Several single-center reviews have been pub-
lished and are presented in Table 9.1. These stud-
ies have consistently demonstrated a high degree
of success in occluding the target vein. Complica-
tion rates have been low, with paresthesias and skin
burns being the most common and vexing problem
with RF ablation. DVT is an uncommon problem
in these series [19]. The imaging follow-up of these
patients (median 25 months) has demonstrated
truncal occlusion of the GSV in 90% with persistent
patency without reflux of the SFJ in the overwhelm-
ing majority of cases [12].
An industry-sponsored registry is being accu-
mulated with published 2-year follow-up data [17].
The patients in this trial were selected to have GSV
<12mm and without significant tortuosity. In this
review 142 limbs were followed up at 2 years with
DUS. Reflux was demonstrated absent in 90% with
significant reductions in pain, fatigue and edema
and 94.6% improvement in symptoms overall. There
ilarization. Complications
were minor, with DVT in 0.7%, PE in 0.3%, skin
burns in 4.2% of the early cases and 0% after the use
of TA, and paresthesias persistent at 2 years in 5.6%
of patients (Table 9.1}.
A single-center pilot randomized trial was per-
formed early in the RF experience comparing pro-
cedure related success and complications of ligation
and stripping to RF EVTA of the GSV [20]. Fifteen
patients were randomized to RF and 13 to surgery
and all patients were followed for a mean of 50 days.
The technical and clinical success and complica-
tion rates were similar. The RF technique was per-
formed without tumescent anesthesia and many of
the described complication would likely have been
avoided with its utilization. Using a visual ana-
logue pain scale, clear advantages were noted for
EVTA most marked from days 5-14 following treat-
ment. Less analgesics and days off from work were
required by the EVTA group. Health related quality
of life assessments ultimately improved to a similar
extent but the EVTA group reached maximum ben-
efit earlier.
Another small multi-center randomized trial
comparing RF ablation to surgical stripping of the
GSV with high ligation has been performed [21]. The
data collected at a mean of 4-month follow-up and
demonstrated that the recovery following RF abla-
tion was shorter than following surgery with a sig-
nificantly higher fraction of patients back to their
usual level of activity at one day following the abla-
tions. Of note was that the recovery was significantly
quicker in those patients treated with RF ablation
using only TA than in those treated with TA along
will] any of he 1 1' torm of anesthesia. QOL ;is assessed
using a standardized instrument was found to be
significantly better immediately after RFA than
after surgery, although by 4 months this difference
was becoming significantly smaller.
Endovenous laser ablation of the great saphenous
vein, short saphenous vein and other saphenous-
related trunks has been approved by the FDA. The
Author
Limb,
hi .1 oiv- ■■.'."
knvl'jdeii ve;
j]/:\i: Ly '.'pea no reflux i
! J ',:\is:he-Lis
DVT
Burns
Ref#
w„™
140
™'r 2
96%
8%/l%@6mc
is.
14
k iSTNt:.
300
97%
N'R
0.7%
0.3%
15
GOLl'M AS
6-24 mos
68%/22%
NR
16
Merchant
232(5'] 2 mo
!./ 12-24 1110
s. 84%/6%@12
mos., 85%/4%@24 mos.
1 5%/6%@24 mc
s. 1%
2.1%
17
(VNUS registrv)
142@24 mo
Wagner
24
3-12 mos
21/21@3 mo;
!. And 3/3 & 12 mos.
1/24
18
is Thermal Ablation of [nccmpeie:'/ Trim.:;!! Veins :n f';'.l ients with v.ioerlicial Venous Insufficiency
valuating the use of laser ablation of the GSV
Limbs Follow-up Sue
reported success rates reported in several single-
center series laser ablation for GSV are presented in
Table 9.2. In these series there were no restrictions
to vein size or degree of tortuosity. These data have
consistently shown successful nonthrombotic occlu-
sion of the target truncal vein in >90% of cases with
very rare recanalizations of previously occluded
vein segments. Clinical improvement was noted in
almost all of the cases with successful truncal vein
occlusion. The incidence of DVT, paresthesias and
skin burns was almost 0% in these series. Most
patients have bruising over the region treated prob-
ably related to the needle injections for tumescent
anesthesia. Many also describe a pulling sensation
about 1 week after the procedure which is thought
to be secondary to the evolution of the inflamma-
tory response from vein wall injury maturing into
a cicatrization phase. Superficial phlebitis was
reported in 5-12% of patients alter laser treatment
noted primarily in cohorts of patients treated with
delayed compression sclerotherapy rather than in
those treated with immediate ambulatory phlebec-
tomy of the larger tributary varicosities.
Optimization ot the laser technique has prompted
an evaluation of outcomes related to treatment
parameters. Zimmett has suggested a lower rate of
bruising and discomfort associate with continu-
ous as opposed to pulsed laser energy delivery [27].
Timperman [10] has shown that the success of laser
EVTA is unity when energy delivery is maintained
on average as greater than 80 [/cm of vein treated.
Kurt lie-]- optimization is likely to influence the out-
come and side effects somewhat. However, given the
high degree of success comparisons of large num-
bers of patients will likely be necessary to establish
any expected subtle difference.
Although speculation exits regarding differences
between laser and RF EVTA success and side effects,
there is no significant published experience com-
paring these two technologies. The important thing
to recognize is that both of these technologies rep-
resent exciting, minimally invasive, low-risk, quick-
recovery options for patients with symptoms or
complications ot superficial venous insufficiency.
Re-canalization ot a treated vein presenting with in
the first few months after EVTA likely results from
insufficient thermal energy delivery. This is either
because of excessively rapid pull back of the thermal
device or inadequate TA resulting in poor transfer of
thermal energy to the wall. Vein diameter probably
has no bearing on the success assuming adequate TA
is applied, regardless of whether RFA or laser is the
source of this energy. Late recurrences can be related
to re-canalization of a previously occluded vein but
are more likely related to development of incompe-
tence in previously untreated vein segments.
Summary
EVTA should be considered a scientifically accept-
able option to eliminate truncal reflux. The pro-
cedures can be performed without sedation in an
ambulatory setting and are very effective, safe and
associated with virtually immediate recovery. EVTA
appears to be associated with a lower rate of recur-
rent SVI due to a virtual absence of the high rate
of groin neovascularity seen with high ligation and
stripping of the GSV. EVTA procedures have already
begun to supplant traditional surgery for truncal
incompetence.
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model.J Vase Interv Radiol 14:911-915
Embolotherapy Applications in Oncology
10 Chemo-Embolization for Liver
Christos S. Georgiades and Jean-Francois Gesi
CONTENTS
10.1 Introduction 129
10.2 Clinical Considerations 130
10.2.1 Patient Selection jn; Preparation 130
10.2.2 Pathophysiology and Anatomical
'Considerations 132
10.3 Technique 132
10.3.1 Procedure 132
10. 3 .1 Recovery 135
10.3.3 Follow-up 137
10.4 Results 136
10.5 Conclusion 139
10.1
Introduction
Chemoembolizaticm is being used with increasing
frequency in the treatment of solid hepatic tumors.
Continued refinements of the technique and better
designed studies have confirmed the survival bene-
fit imparted bychemoembolization on patients with
unresectable liver cancer, though still being consid-
ered a palliative option. While no conclusive data
exist as to a survival benefit for patients with hepatic
tumors other than hepatocellular carcinoma (HCC),
this procedure is rapidly gamins favor over other
nonsurgical alternatives (see below). HCC is the
most common solid, nonskin cancer in the world,
with an especially high prevalence in Southeast
Asia and Sub-Saharan Africa. The main predispos-
ing factor in these geographic regions is Hepatitis B
(the strongest risk factor associated with developing
HCC), whereas in Europe and the USA the increasing
incidence is attributable to a concomitant
C. S. Georgiades MD, PhD
Assistant Professor of xockobgy and y.irgei v. Johns Hopkins
Medical Institutions, Blalock 545, 600 N. Wolfe Street, Balti-
more, MD 21287, USA
J.-F. Geschwind.MD
Associate Pro] ess.: 1 : of ka^iologv, ?;::gerv aiv.i 0:- oology, lohr.s
Hopkins Medical Institutions, Blalock 545, 600 N.Wolfe Street,
Baltimore, MD 21287, USA
in the incidence of Hepatitis C(three-fold from 1993
to 1998) and alcoholic cirrhosis [1]. Epidemiologic
analyses project increasing incidence in cirrhosis
and HCC in the USA for the foreseeable future [2,3]
and the trend is expected to eclipse the 70% increase
in incidence of HCC over the last twenty years [1],
Though less frequent, the incidence of cholangio-
cellular carcinoma (CCC) in the USA is also on the
increase with approximately 4,000 new cases per
year. HCC and CCC comprise the overwhelming
majority of primary malignant hepatic neoplasms.
Secondary or metastatic hepatic neoplasms are espe-
cial!)' common owing to the blood tilt rat ion In notion
of the liver. With prolonged life expectancy, more
people develop cancer and with improved cancer
treatments patients live longer and thus have a
greater chance of developing liver metastases. These
factors have contributed to the ever-increasing inci-
dence of patients with secondary hepatic neoplasms,
especially in the Western World. Whether primary
(HCC, CCC) or secondary however, hepatic malig-
nancies carry a dismal prognosis with overall long-
term survival percentage rates in the single digits.
Both HCC and CCC are slow-growing tumors and
even when the presence of risk factors initiates
some sort of surveillance (cross- sectional imaging
or tumor markers such as alpha-feto protein (AFP))
the majority of patients are unresectable at presen-
tation. Of the 10%-20% of patients with HCC who
are deemed resectable most will recur even with
optimum treatment either due to residual tumor or
metachronous lesions that eventually will develop in
a cirrhotic liver. Liver involvement with metastatic
disease from solid tumor imparts an equally dismal
prognosis. A patient with resectable liver metasta-
ses and controlled primary disease who can benefit
from such aggressive treatment is the rare exception.
Median survival for patients with unresectable liver
cancer is disappointingly short irrespective of his-
tology. Survival ranges from a short two months for
patients with adenocarcinoma of unknown primary
to a maximum median survival of 15 months for
colon metastases. Carcinoid patients in particular,
'._". S. Geoigiodes ond l.-H G esc hrdnd
have very slow disease progression and despite the
presence of liver metastases may survive for years.
Survival for unresectable disease from hepatocellu-
lar carcinoma, ehokuisioairdnoma, and metastases
from pancreatic, breast cancer, and melanoma are
between 4 and 9 months [3-9].
These disappointing results coupled with the
poor response of HCC to traditional chemotherapy
have provided the impetus for the development of a
variety of nonsurgical techniques for the treatment
of hepatic neoplasms (Table 10.1). Such techniques
are generally divided into transarterial interven-
tions versus percutaneous ones. The latter group is
further subdivided into thermal ablation techniques
versus chemical ablation techniques.
Transarterial chemoembolization (TACE) has
become the most popular locoregiona! technique
for the treatment of unresectable HCC. Llovet etal.
[10.] showed for the first time that TACE imparts a
survival benefit to patients with unresectable HCC.
It should be mentioned that some institutions do not
routinely use chemotherapy during embolization
for primary or secondary unresectable liver can-
cers. Though data show such patients who receive
TACE have a longer survival and/or better response
than those receiving blunt transarterial emboliza-
tion (TAE) only with kipiodol (Savage Laboratories,
Melville, NY), Gelfoam (Pharmacia and Upjohn,
Kalamazoo, Michigan) or particles (PVA by Boston
Scientific or Embospheres by Biosphere Medical
Corp., Boston, MA), the difference is not statistically
significant [10-13]. The reason that the differences
inpatient survival between chemoembolization and
blunt embolization are not significant is probably
the small number of patients in the relevant studies.
Chemoembolization should reasonably be expected
to effect greater response not only pathophysiologi-
cally; studies (despite lack ot statistical significance)
always show greater survival for patients treated
with TACE versus TAE.
Table 10.1. Nonsurgical
Nonsui g ic.d
Percutaneous
Thermal ablation
ns for unresectable hep.;l
:-ioiiiii:'.g hematic neoplas
10.2
Clinical Considerations
10.2.1
Patient Selection and Preparation
In addition to improved survival for patients who
undergo TACE for unresectable disease, there have
been reports of patients whose tumor has shrunk
enough to permit resection or liver transplanta-
tion and provide a chance for cure. Despite these
benefits, TACE is considered a palliative treatment
option. Surgical resection is the only procedure that
can be performed with curative intention, therefore,
TACE should be reserved for patients who are not
surgical candidates. This is the only absolute con-
traindication to TACE. Table 10.2 summarizes a list
of relative contraindications.
Prior to TACE all patients should undergo a
gadolinium-enhanced [Omniscan, GE Healthcare,
Princeton, NJ] MRI of the liver, preferably with per-
fusion^ iff usion sequences (Fig. 10.1). CT, without
and even with contrast cannot adequately delineate
viable tumor and differentiate it from necrosis, scar,
or inflammatory tissue. CT can follow the tumor
response as far as size goes, but we believe this is
inadequate, whereas enhancement on MRI perfu-
sion imaging provides more accurate information
on which part of the tumor is viable and which is
Dual phase, contrast-enhanced MRI with perfu-
sion sequence will not only delineate the extent and
viability of tumor but also serve as a baseline study
to plan future treatment. A simple dual-phase MRI
or CT is acceptable as well but inferior to MRI per-
fusion in quantifying viable tumor. In addition to
information regarding tumor viability and morphol-
ogy, cross-sectional provides information regarding
the tumor's vascular supply and anatomy. For exam-
ple, knowing the presence of portal vein thrombosis
malignancies
I nira- arterial
lation TACE TARE
m ;:":'
RFA
Cryo
All of the cerci.it.;:' eons ieckn.iqces are Incited oy die size and number of the lesions i up to three lesions e.;cii measuring up :c
■i cm i as wed as dieir loci; lion. Miochaphiag:r.atic lesions r.iav oe peiccianeecsly inaccessible, and lesions close to l. : :ge v.i-cula:
structures respond ceo: ly to tliei ma I iiKade:'. techniques ; XrA, N'CT, Cryo. and LI PC). On ihe contrary, '
are not limited by the numner, size, or location of ihe lesions; rather by the hepatic function reserve
TACE, trans-arteriai chemo-rniooiizaiion; TARE, irans-aicerkk rarho -embolization; MCT, microwave ci
radio frequency ablation; L1PC. laser inteistida! photocoagulation; Cryo, cryo- an Lit ion; PEl, percuta:
PAAI, percutaneous acetic acid inaction; PCI. perccianeecs chemotherapy injection
arterial techniques
is shown in Table 10.2.
■guhidor. theracv; UFA.
!ous ethanol injection;
Chemo-Embolization for Liver
Table 10.2. Contraindications
Contraindications to TACE
: . Borderline liver fundi on
2. Total bilirubin > 4 mg/dl
3.Albumin<2
4. Encephalopathy
5. Coagulopathy
6. Poor general health
7. Signifies]
S.EIevaied
Mitigating action
1-3. Super selective TACE of :. hepanc segment may be considered
4. TACE may be performed .f encephalopathy was minimal.
Consider lactulose.
5. Give FFP or platelets as indicated
6,7. See below
8. Mucormist p.o. and i.v. fluids if creatinine > 1.2 but < l.S.
shu:'.:iiig 111 rough I he minor Avoic, "ACE [f Cr > 1.7
Borderline liver function, eiscephaleprili'.y, .ind poor general heallh nre subjective factors, and liie complete clinical picuire
T.ust be considered prior ;o deeding wheiher to proceed ivi:)i TAC1-1. Cl'.i.d-f'r.gh C .iver disease pjuenls show poor r espouse io
TACE, and in general we avoid TACE in such patients. On the other hand, Child-Pugh A liver disease patients seem to obtain the
T.axiiV.iiT. hei;ef: \ from TACE. exhioitmg :he longest - : n iv.vo I. Though we do use TACE for Child-Pugh K liver disease p.;t;eijis,
their survival benefit is less tr.an ilia I of rl'.eir stage A counterparls.Toial bilirubin of -i mg/dl is c.irreniiv used ji our ins I it 1 .;; ion
its Lie c.::-off. Wr have recemly .n creased tl"..s fro::i .1 ::ig,'d. without :;ny adverse effects. Uiipso.ished o : .\la jgjin f: e:v. our insti-
:uti::ui have show: 1 . Mi a: port, 1 . 1 ve:n tliiomoosis Joes not increase ihe risl-: of complications, at leas: in Cl'..ld-A paiie:t:s. Hnally,
.'.: :eiiove:'oiis sliunl .no ; li r" : i.: u :"i die i 1 1 n '.-."■ I ."an resu.i .:". :".■ ■::;.■ i gd emhu'ai.o:".. I'h.s .s ev ..." em on i.:e initial angiogram, and
o lu nl Celfoam eniboliz.'.tion can eliminate :lie sriunoing and allow rlie pa:ien: to proceed wiih T AC 1-1. A: our institution arterial
access is avoided if INR > 1.7 or APTT > 1.7 or platelet count < 50,000.
and/or variant vascular anatomy may obviate the
use of embospheres during treatment or reduce the
procedure time and contrast load. Patients are pre-
medicated depending on the tumor histology, renal
function, and prior surgical and medical history.
For example, patients with carcinoid will have to be
premedicated with Sandostatin to prevent possible
carcinoid crisis after TACE. At our institution we
have thus far performed TACE in patients with car-
cinoid metastases to the liver more than a few hun-
dred times without witnessing any carcinoid crisis.
Patients whose sphincter of Oddi function has
been eliminated, i.e. hepatoiejii rtostomy, sphinc-
terotomy patients or patients with percutaneous or
internal biliary stents, are at high risk (> 50%) for
developing a hepatic abscess after TACE. Stringent
24-h bowel preparation and i.v. administration of
broad- spectrum intravenous antibiotics prior to the
procedure is recommended, but abscess formation
is still likely. This is thought to be a result of coloni-
zation of the biliary tree secondary to a resected or
incompetent sphincter of Oddi. TACE causes isch-
emia to the biliary tree which, unlike liver paren-
chyma, is exclusively supplied by the peribiliary
plexus via the hepatic artery. The necrotic tumor
bed may become infected and abscessed, which can
be particularly difficult to eradicate even with per-
cutaneous drainage and i.v. antibiotics. This compli-
cation should always be discussed with the patient,
with anoverallriskof abscess formationof50%-70%
mentioned. Laboratory values should be obtained
prior to TACE, including: A comprehensive meta-
bolic panel (NA, K, glucose, creatinine, BUN, total
Fig. 10.1. Axial, venous phase, ga a o.inium -enhanced MR!
of a patient with unresectable HOC showing a peripherally
enhanced lesion huroii'sl in die medial segment of the left
lobe. Solid, well demarcated lesions such as this ^nii respond
better to TACE than do diffuse or multifocal lesions. Addition-
ally, hyper vase u I ;ir tumors appear to respond better to TACE
showing a higher degree of necrosis on follow-up MRI
bilirubin, AST, ALT, alkaline rahephatase, albumin,
total protein), hematology panel (hematocrit and/or
hemoglobin, white blood cell count, platelet count,
coagulation profile (INR, APTT) and tumor mark-
ers (i.e. AFP for HCC, CEA for colon cancer). These
values serve not only to ensure a safer procedure
(i.e. normal coagulation) but also to allow for proper
tollc.v-iip ol hepatic and renal I unction and n
response (using tumor marker levels). Finally, s
the procedure is performed under sedation, an
NPO status is required.
'._". 3. ije'.'igudes .in..: [.-!-'. Gesdiuiij.i
10.2.2
Pathophysiology and Anatomical
Considerations
Chemoembolmilion lakes advantage of the fact that,
while normal liver parenchyma receives most of its
blood supply (60%-80%) from the portal venous
system, malignant hepatic tumors, whether pri-
mary or metastatic, are nearly exclusively supplied
by branches of the hepatic artery. Cancer angio-
genesis (a.k.a. neovascularization) is a process by
which neoplastic cells recruit new blood vessels in
order to ensure adequate local oxygen tension. Due
to their relatively higher metabolic demands cancer
cells live in a nearly constant state of hypoxia. They
respond by secreting chemntactic factors that pro-
mote the formation of new blood vessels. Arterial
epithelial cells are much more responsive to these
factors, which explains why such malignant tumors
are supplied by the hepatic artery. Chemoemboliza-
tion then selectively targets the tumor while liver
parenchyma is mostly (but not entirely) spared. The-
oretically then, chemoembolization can be used to
treat any solid malignant hepatic neoplasm whether
primary or metastatic, solitary or multifocal, and
irrespective of size. Of course exclusion criteria do
exist and are described in detail below. Accessory
and/or replaced right or left hepatic arteries are
n (up to 20%-30%). Usually such variations
sequential, but rarely they may render
catheter-selection of the hepatic artery to be treated
with the 5 Fr catheter difficult (see Technique sec-
tion below). Even then a 3 Fr microcatheter is usu-
ally a successful alternative. In addition, common
origins ol the leit hepatic and left gaslric .'is '■veil m
right hepatic and right gastric arteries maybe added
complicating factors. Such associations are impor-
tant insofar as they increase the risk of nontarget
embolization, mainly the stomach, proximal small
bowel, and/or pancreas. Though self limiting gastri-
tis, duodenitis and pancreatitis have been reported,
no deaths have yet been documented from nontarget
embolization. Vigilance during the initial diagnostic
arteriogram and intimate knowledge of the related
vascular anatomy and its possible normal variations
is a must in order to minimize the chances of com-
plications. Recently, a few published reports have
described extrahepatic supply of liver cancers. For
example, intercostal or diaphragmatic arteries can
be recruited by neoplasms. If repeated TACE fails to
show the appropriate response or if a section of the
tumor remains viable while the rest shows signifi-
cant necrosis, search for such extrahepatic supply
is indicated. Selective arteriograms of intercostal
and diaphragmatic arteries or a 3-dimensional CT
angiogram can determine whether indeed this is
the case. Currently, portal vein thrombosis (PVT)
(Fig. 10.2) is considered by most physicians as a con-
traindication to TACE for fear of causing hepatic
ischemia/infarction and possible decompensation.
However, unpublished data from our institution
confirm that for Child-Pugh A or B patients TACE
is a safe intervention even in the presence of PVT.
We had no mortality of significant morbidity for
30 days post-procedure in these patients. In addi-
tion we showed a survival advantage compared to
historicalcontrols.
10.3
Technique
10.3.1
Procedure
After a treatment plan is formulated based on image
findings and the patient's clinical situation, informed
consentis obtained. Informed consent should disclose
the following risks: Injury to blood vessels and/or
organs (which may require blood transfusion or sur-
gery), anaphylactic reaction to contrast, worsening
of renal function, infection, liver function worsening
or liver failure and possibly death. Appropriate i.v.
antibiotic prophylaxis is administered (cefoxetin 2 g
i.v. once, at our institution) immediately pre-proce-
dure. Preprocedure documentation of femoral, dor-
salis pedis and posterior tibial pulses is mandatory in
order to choose the appropriate access site (strongest
pulse between right or left common femoral artery,
CFA) and compare with the post-procedure exam for
any changes. The patient is placed on the fluoroscopy
table supine and both groins are prepared and draped
in a sterile fashion. Sedation is provided according
to the local nursing protocol (i.e. Versed and Fen-
tanyl, supplemented as needed with Phenergan and/
or Benadryl).
• Step 1-Obtaining vascular access. In most cases
access using an 18 g, single-wall needle followed
by an 0.035" guide-guide wire is successful. In dif-
ficult cases a 0.018" micropuncture set can be of
help, with or without the use of ultrasound guid-
• Step2-Maintaining access. A 5-Fr short vascu-
lar sheath providing access in the right or left
(strongest pulse) CFA is used at our institution.
Chemo-Embolization for Liver
Fig. 10.2. Antero-posierior, riigii.il subtraction angiogram of
the abdomen of" a patient with unreiiech.ible HO.] showing clot
in portal veins. This arterial phase hepatic angiogram shows
early arterial-port;'.! venous shinning through a hypervascu-
lar tumor (white arrow). The shunting into the portal veins
uncovered a ill ling defect (dor) in die main ! bhii:k onowlioiui)
and left i whit? jiii>ir/i ( ':i,i) portal veins, embolization with 1
cc of" Gelfoam slurry shut down the shunt while the tumor
supplv was preseived. This allowed us to proceed with TACE.
The presence of portal vein IhioinPosis should not be consid-
ered by itself as a com::iii;dical.oii to TACE. "Unpublished data
from our institution shows TACE to be a safe and effective
procedure in Child-Pugh A and B patients
A 4 Fr access set can be used in cases where less
traumatic arterial access is needed (i.e. slightly
abnormal coagulation profile, severe peripheral
vascular disease), however smaller catheters may
be a bit less controllable.
• Step 3-Abdominul ;ioi Togi'am. (Optional). A flush
aortogram via a multisideholed, pig-tailed cath-
eter at the level of the celiac artery will delineate
the vascular anatomy, tumor supply and provide
a road-map for more selective access. For the most
part this step am be skipped. In rare cases and after
failing to easily select the SMA and celiac axis with
a selective catheter (see step 4), which may suggest
variant anatomy, one may revert to an abdominal
aortogram. If performed, a 15 cc per second injec-
tion for a total of 50 cc (15/50) is adequate.
• Step4-Selective arteriograms. First, a 5-Fr glide
catheter (Simmons-1 or Cobra glide-catheters,
Terumo Medical, Somerset, NJ) is used to select
the superior mesenteric artery (SMA) and per-
form a prolonged angiogram that is carried well
into the venous phase (Fig. 10.3).
■ An injection rate of 6 cc per second for a total
of 40 cc (6/40) is what we use. If the portal vein
is proven patent on recent MRI, CT or previ-
ous angiogram, the portal venous phase can be
skipped, lowering the injection rate to 6 cc per
second for a total of 20 cc (6/20). Then the celiac
artery is selected (again Simmon's I or Cobra
glide catheters) and a selective arteriogram is per-
formed with an injection rate of 6 cc per second
for a total of 20 cc (6/20). In most cases the celiac
axis arteriogram will show the tumor blush to
best advantage (Fig. 10.4). Prior to power-injec-
tioii angiography using a mechanical injector, one
should perform a gentle, short contrast injection
by hand. This will serve many purposes: (1) it will
ensu re the catheter is in the right position, (2) that
its tip is not in a small side branch (inadvertent
power-injection in a small branch may cause dis-
section and/or thrombosis), and (3), it will give an
idea on how fast (or slow) the flow is in the vessel
of interest. The above-mentioned injection rates
can be tailored to the flow observed within the
vessel of interest. If for example the blood flow in
the SMA appears to be very slow, instead of the
usual 6/20 injection rate one can lower it to 5/15.
Likewise, if the flow is fast or vessel caliber large
the injection rate can be increased to 7/35.
Fig. 10.3. Ante
the abdomen
phase shows ;
') and left (Jong U
or. digital subtraction angiogram o:
.t with multifocal HCC in the venous
ain (double arrows) as well as right
row) portal veins. Though only a rela-
tive contraindication, po:ta' vein thrombosis demands \
precautions to avoid complete cessation or" flow in the hepatic
artery and to limit the use of embolization material (such its
Gelfoam or particles] during TACE
'._". 3. Geoigudes .in..: [.-!-'. GesdiHind
Fig. 10.4. Antero-poslciior, digital subtraction angiogram i:'.
the arterial phase during celiac artery contrast injection in
a patient Willi HCC (same as rig 10. 1) shows an enhancing
lesion (iicrpiri'i supplied by ijie let", brpatic ai ;ery. High tumor
vascularity ("blush") is a marker for successful TACE
■ Step 5-Selecting the finalcatheter position. A glide
0.035" wire is advanced through the glide catheter
followed by the catheter itself. Though one wants
to be as selective as possible to avoid chemoembo-
lizing normal liver, being too selective will result
in parts of the tumor not being treated. In gen-
eral, either the right or left main hepatic artery is
the optimal position for the treatment catheter. In
cases where there is tumor in both lobes, the one
showing more tumor blush during the diagnostic
celiac (or SMA) arteriogram should be targeted. If
the 5 Fr glide catheter cannot be advanced to the
desired location because of unfavorable anatomy,
a 3 Fr microcatheter (Renegade, Boston Scientific)
over an 0.018" guide-wire (i.e. Transend, Boston
Scientific) can be used coaxially. If one is target-
ing a peripheral solitary lesion, then one can be
as selective as possible provided the whole lesion
is targeted. In our experience the more selective
the catheter is the higher the degree of necrosis.
During this step, the radiologist may observe
arteriovenous shunting through the tumor. If one
proceeds with TACE, one risks nontarget embo-
lization (lungs, since the most common type of
shunting is hepatic artery to hepatic vein) and
inadequate tumor treatment. Instead, the opera-
tor should treat first with blunt embolization
using Gelfoam until the shunting resolves. If at
the end of blunt embolization the tumor is still
enhanced by contrast then one can proceed with
TACE. Otherwise a 2-week wait period is recom-
mended at which time a repeat arteriogram will
decide whether TACE is possible.
» Step 6-Treatment. TACE is performed slowly by
hand-injection under continuous, real-time fluo-
roscopy to ensure there is no reflux of chemother-
apy back around the catheter that may result in
nontarget embolization. Though nontarget embo-
lization of the contralateral hepatic artery may
not be a serious problem, inadvertent emboliza-
tion of the gasiroduodenal artery can have serious
consequences including gastroduodenal necrosis.
Single, double, or triple agent chemotherapy mix-
tures are used with varying frequency depending
on institutional preference. At our institution we
use triple chemotherapy mixture composed of
100 mg Cisplatin (Bristol Myers Squibb, Princ-
eton, NJ), 10 mg Mitomycin C (Bedford Labo-
ratories, Bedford, OH) and 50 mg Doxorubicin
Hydrochloride {Adriamycin; Pharmacia- Upjohn,
Kalamazoo, MI). Currently there is no data as
to the relative efficacy of specific chemotherapy
mixtures. The chemotherapy is mixed 1:1 with
Lipiodol (Savage Laboratories, Malville, NY) (2:1
if slow flow is noted in the artery to be treated}.
Lipiodol has been shown to concentrate within the
ulature and reside there for weeks,
incentration of chemotherapy
in the tumor by up to 100-fold compared to sys-
temic chemotherapy. After chemotherapy infu-
sion, 10-20 cc of nonbuffered lidocaine can be
infused through the same catheter for pain con-
trol. This provides not only immediate pain relief
in case the patient complains of intra-procedural
pain but has also been shown to help in the imme-
diate post-procedural period and until patient-
control anesthesia can be initiated (see below).
Additional embolization with 150-300 microm-
eter particles (PVA, Boston Scientific or Embos-
pheres, Biosphere Medical, Boston, MA} until the
flow in the treated artery is slowed down, further
increases the chemotherapy residence time within
the tumor, though data related to actual benefit
are lacking. At our institution, complete embo-
lization is avoided for two reasons: (1) we want
to ensure patency of the artery for future treat-
ments, and (2), in vitro experiments have shown
that prolonged hypoxia induces selection for more
aggressive neoplastic cells. Table 10.3 shows the
list of materials requ ired for TACE and Table 10.4
shows the possible complications and associated
mitigating measures.
Chemo-Embolizi
Table 10.3. The basic materials n
Aliein.-
Obtaining arterial
Maintaining arterial
18-g single-wall needle (Cook") and 0.035"
guide wire (Bentson, Cook)
5 Fr, 11-cm vascular sheath : Cordis' 1 i
IV: toiiiiii'.g aodc:'.:i:'.a! a h. htaail-rlusri cath^.er ; .Ang;.: ,"vn.'
aortogram
Pc: forming selective 5 Fr, hook, enci'.cle glide catheter (Sin
SMA& celiac Terumo")
arteriogram
Selecting the final Simmon's 1 or Cobra (Terunio) glide t
catheter position over 0.035" glide wire (Terumo)
T:v.- 1 :•/. eni
a-cc syringes and chemotherapy r«
stop-cock
Manual hemostasis
Micropuncture set (Cook)
4 Fr, 1 1 -cm vascular sheath (Cordis)
ics") 4 Fr, Pigtail-flush catheter (Angiodynamics
.on's 1, Cobra (Teiiiino i or Michelson (Angiody-
heter 3 Fr miciocataeter i Renegade, Boston Sci-
entific 3 ) coaxially through the 5 Fr or 4 Fr
catheter over a 0.018" -wire (Transend,
Boston Scientific)
it 3-way 1-cc syringes may be necessary if high res]
tance in micro catheter
Closure device
7 Finishing
7 lie micro catheter ; step 5 ; :s used only if :be Simmons ] glide- cannot be advanced iai eiv aig:: to satelv miiise tae chemcaherapy
mixture. Once ready v: infuse, the chemolhei aay and related supplies slv ■ li 1 J be manipiLa:eo at a table separate {:<:::: the main
one, to avoid inadveitenl chemotherapy contamination or unrelated supplies.
■■ Cook, hlooaiar.gLOn, IN: Cordis. Miaiv.i. !-L; A ngic-cy ramies, ^ueeiisouiy, NY: 7e; una:. Soi'.ieisel, Ml: K.:- J -^a:: Scientific, Boston, MA
» Step 7-Finishing. A single high-resolution expo-
sure of the liver is obtained to document distribu-
tion of Lipiodol (along with chemotherapy). The
catheter and sheath are removed and hemostasis
is achieved with manual pressure or the use of a
closure device. Peripheral pulses are rechecked
and documented to make sure they are stable.
Though exceedingly rare with proper technique,
significant changes may signify complications
such as access artery dissection or distal throm-
10.3.2
Recovery
1 of the common femoral artery vas-
cular sheath and proper hemostasis is achieved,
the patient is placed on monitoring for 4-5 h and
patient controlled analgesia (PCA) pump and i.v.
hydration are initiated. At the end of the monitor-
ing period and if no untoward events are noted
the patient is sent to the floor. Routine nursing
checks and care are adequate thereafter. P.R.N,
medication should include (in addition to the
morphine or fentanyl PCA pump), anti-nausea
and additional pain medication for breakthrough
pain. Hydration is critical not only because of
the patient's NPO status prior to the procedure
and possible nausea, but more importantly to
mitigate the consequences of a possible tumor
lysis syndrome such as acute renal failure. After
the 4-h observation period the patient is encour-
aged to ambulate, initially under supervision.
Table 10.5 shows a sample admission order sheet.
The use of arterial puncture closure devices can
cut down the observation period to 2 h. As soon
as the patient ambulates, the Foley catheter (If
one was placed) is removed. At the same time p.o.
intake is advanced as tolerated. When the patient
is ambulatory a noncontrast CT of the abdomen is
obtained to document the distribution of Lipiodol
and the degree to which the tumor has taken up
the chemoembolization mixture (Fig. 10.5). Uni-
form Lipiodol uptake by the tumor correlates with
a higher degree of necrosis compared to spotty
or lack of Lipiodol uptake. Likewise, region with
high Lipiodol uptake post-TACE correlate with a
higher degree of necrosis on follow-up imaging
examinations (Fig. 10.6).
After a 24-h period of observation and symp-
tomatic control, the patient is discharged to home,
barring continued significant symptoms and with
appropriate instructions to exercise vigilance for
possible infection or groin hematoma. A sample dis-
charge form is shown in Table 10.6. More than 90%
of TACE patients are discharged to home after this
period. Cases which require one more day of hospi-
talization are rare and even longer stays are exceed-
ingly rare. Discharge medications should include a
7-day course of oral antibiotics (i.e., Ciprofloxacin
250 mg p.o. bid) and P.R.N, pain medication.
C. S. Georgia des and [.-!-. Citsc hwind
Table 10.4. Possible complic:
iated with TACE
Nontarget embolizatio
Post-embolization syndrome
(Pain, fever, nausea /vomiting I
Tumor lysis syndrome
n of TACE Mitigating intervention/notes
n, and gastric acidity reductic
Pre- and post-procedure liyii j r:1 _■:■ n
Follow creatinine
LFT elevation Follow as outpalieni if mild and asymptomatic
Liver failure Avoid TACE in patients with Child-Pugh C liver disease. Do not perform TACE from proper
hepouc artery. Selec.l right or left. Mjv be irreversible and fatal
In our experience at leas; halt I he p.meiiis unJei going TACE will exhibit svmpioms re I ale J 10 postembolizati on to n lesser or
greater Jegree. The vast maionty i '.■■■ 90%) of patients will recover enough to be discharged the next morning. The rest may
require a second hospital Jay. l-'ulahlies related to TACL are exceedingly rare anc. re late J to limited liep.ilic function reserve an J
ensuing liver Jecompeitsalion i;nJ acute failure. It is thus crucial to document the patient's liver ftmciion reserve anc: follow
the contraindications indicated in Table 10.2.
n orders for patients after TACE
Table 10.5. Sample aJm
• Admit: (Attending ni
• Diagnosis: Liver neoplasm, s/p chemoembolizalioii
• Condition: (i.e. stable]
• Vitals: Q 15 min x 4, then q 30 x 2, then hour x 2, then floor routine
• Allergies: (i.e.NKDA)
• Activity: Right (or left) leg straight x 4 h and head flat x 1 b. Tit en ambulate under supervision x 15 min. Then
patient may walk but avoid stairs/straining
• Nursing: Right tor left : groin cliecks q 1 :■ ntin x 4, tit en .: 30 min x J, tit en .: hour x 1 for possiole hem atom a /bleed
• Diet: Advance as tolerated (tailor net patient, i.e. diabetic, low cholesterol etc)
• iVF: 1 00 cc/ri x 1-i h. Lien J/c if pit Lent tolerates p.o-. intake I tailor per patient :
• Meditations: Patient controliec. anesth.es. a pump I P ■: !! A pump, separate order sheet)
- i i.e. femanvl JO meg i.v., .t I min, lock ■"■lit at maximum o limes per hi
- Oxycodone
- Tylox 1-2 tablets q 4-6 h prn breakthrough pain
- Zofran 8 mg p.o. q8 h prn nausea
- Ciprofloxacin 250 mg p.o. bid
• Laboratories: None necessary (tailor to patient!
■ Studies: CT abdomen without i.v. or oral contrast after patient able to ambulate
urJers should be tailored according to specific patient needs. For example, medications should be compatible- with the pa item's
a i.e iiiies: trie amount or i.v. fluids should take into account I he pal le ill's jejt.il function and carJiac status, and la o oratories should
be used to follow suspected TACE toxicilies ! i.e. .^n elevated oikrubin should be followed, as should an elevated creatinine)
Fig. 10J5. Axial, nonenhanced CT of a patient with HCC (same
as in Figs. 10.1 and 10.4) obtained one day following TACE.
shows the lesion retaining the radio-opaque Lipiodol {ai'ivv, )
in its most vascular regions. The retention of Lipiodol - and
consequently c h em otiierapy since tiie two are mixed - can per-
sist for weeks after TACE and cot relates with tumor necrosis
Chemo-Enjbolizadon for Liv
Fig.10.6a-c. Axial CT image of the liver of a patient with unresectable HCC a. The
patient is one day post-TACE. Lio:oco, !i',!gh-iiensi:y regLor.?; i- - : een scattered through-
out the large righ: i it ili mor. A :egi ;n of rel.'tive.v ;::g!ir:' Lipii -. I - ■ I npr;ikc iviiliin [lie
turaor is noted {white iinvivhccut). Six-weel-: MR! fo.kiv-up b shows a partly necrotic
tumor with cystic degeneration o: the l;:im:--:' corresponding 10 [.:e region of high Lipi-
odol uptake (' iWu'rc iimiiic/il'l;:/). Gross palho.oeic.il specimen of die liver c confirms
focal necrosis of the same region {white arrowhead)
10.3.3
Follow-up
11 benefit, patients should Lie seen at reg-
ular intervals, ,1 perfusion MRI of the liver obtained
(Figs. 10.7 and 10.8) and compared to the baseline or
previous MRI. Six-week intervals between successive
TACEs is currently the standard at our institution.
Prior to each TACE the MRI will establish tumor via-
bility (or necrosis}. Necrosis is quantified as 0%-25%,
25%-50%, 50%-75%, and 75%-100% based on perfu-
sion (or contrast enhancement) MRI. If no residual
viable tumor is noted, a follow-up MRI is scheduled
for 6 weeks later and no TACE is performed. Lack of
satisfactory response after one TACE does not pre-
dict eventual response, and additional TACE should
target the same tumor. We have observed many times
patients having "failed" to respond to the first TACE,
responding very favorably after the second or third
TACE. Before TACE is called a "failure" we believe the
patient should be treated at least 2-3 times targeting
the same region. The emergence of any contraindica-
tions to TACE between successive TACEs precludes
repeat treatment; thus prior to each procedure the
relevant laboratory values should be obtained and
the patient re-evaluated. In some cases where the
patient was precluded from having surgery solely due
to tumor size, adequate reduction in size following
TACE may render the patient operable. Though rare,
we have had at least five patients in the last 2 years
who became resectable or candidates for liver trans-
plantation after TACE reduced the tumor burden or
shrunk it away from vital structure such as portal/
hepatic veins. Thus continuous re-evaluation and
consultation with oncology and surgery is vital so that
such patients do not miss a chance for cure. Finally it
should be noted that TACE-associated toxicity is sig-
nificantly less than that of peripherally administered
'._". S. Georgia des and [.-!-. i."iesc lnvind
Table 10.6. Sample discharge ir
is for patients after TACE
.e all i.v. lines
- Ciprofloxacin 250 mg p.o.bid x 7 days
- Oxycontin 10 rag p.o. ql2 h prn pain
- Oxycodone 5-10 rag p.o. q 4-6 h prn breakthrough rain
- Zofran 3 nig p.o. q8 h prn nausea
• Instructions: - No straining, stair clinibing, or driving x 48 h
- If groin swelling or bruising, or fever, natisea/vomiiing.
or worsening abdominal pain call (on call number)
• Diet: - As tolerated
• Follow ■:.-. \ - Con; r.isi -enhanced MKi of iiiv: .mo same cay cl.n.c appointment
with (Intervemional Kadioiogisi! in 4-6 weeks
• Send copy of discharge summary to ! referring physician's name)
■' Ti'.ese are gener.'.l guidelines. Specific instructions should be tailored to patient's
needs, allergies, and clinii
• Discharge k
Fig. 10.7. Axial. gadolinium enhanced MR! of the liver of a
patient with HOC shows a Luge, peripherally enhanced lesion
(arrows) replacing the right lobe. The patient was unresectable
owing to the size ji the tumor. I 'ecision was made to treat the
patient with TACE for palliative reasons
Fig. 10.8. Axial, ga c cl in in m- enhanced MR! of the liver of the
same patient as in Fig. 10.7 after two TACE treatments shows a
dramatically decreased in size I timer with decreased enhance-
ment (iirrpii-'s). Though in any tumors may not decrease in size
significantly after TACE, most will show a degree of necrosis
as measured on contrast-enhanced MR!
chemotherapy (unpublished data, C. S. Georgiades,
K. Hong, M. W. D'Angelo, J. F. Geschwind). Of
course the main drawback of TACE is that it does not
treat metastases outside the liver, which are in any
case rare for HCC. For many secondary hepatic neo-
plasms, liver metastases are indeed the life-limiting
disease aspect and such patients may benefit despite
the presence of extrahepntk metastases.
10.4
Results
TACE is c
able and o
e of the most popular techniques avail-
e that is rapid ly gaining favor. Despite the
fact that it has been used world-wide for many years,
there has been, until recently, a lack of prospective
randomized trials regarding its efficacy. Because
of this, the procedure generated considerable dis-
cussion and dissent among physicians. Skepticism
has been finally put aside by one randomized con-
trolled trial and a recent meta-analysis that con-
cluded that TACE significantly improves survival
of patients with nonresectable HCC compared to
nonactive treatment. Llovet et al. [10.] performed
a prospective randomized trial that recorded a 1-,
2-and 3-year survival of 82%, 63%, and 29% for
patients undergoing TACE vs. 63%, 27%, and 17%
for patients treated symptomatica lly. As a matter
of fact, the trial was terminated early when the sig-
ii! Meant survival benefit of the TACE group became
evident. Cam ma etal. [14] performed a meta-analy-
sis of randomized controlled trials looking at the
two-year survival of patients with unresectable HCC
who underwent TACE, transarterial chemotherapy
(TAC) or transarterial embolization (TAE) versus
nonactive treatment. Patients who underwent tran-
sarterial treatment had significantly improved sur-
vival with a pooled odds-ratio of 0.54 (95% CI). The
TACE and TAE groups had an odds-ratio of 0.45
(95% CI) and the TAC group an odds-ratio of 0.65
(95% CI).
Prospective, randomized trials investigating pos-
sible survival benefits of TACE for metastatic neo-
plastic disease to the liver are lacking, as are such
trials for cholangiocarcinoma. From our own expe-
rience however (accepted for publication, March
2005, JVIR), patients with unresectable cholangio-
carcinoma treated with TACE had a median survival
of 23 months, compared to only 6 months for histor-
ical controls receiving supportive treatment alone,
9 months for those receiving systemic chemother-
apy and 16 months for those receiving chemoradia-
tion. Metastatic colon cancer to the liver has proven
to be less responsive than hoped for to TACE, with
reported median survival of 10-12 months. Still,
patients with colorectal metastases to the liver resis-
tant to systemic chemotherapy may obtain benefit
from TACE [15-17]). Other metastatic neoplasms to
the liver that are amenable to TACE include carci-
noid, breast cancer, adrenal cancer, sarcomas etc.
From our own experience, though technically fea-
sible for all types of pathology, TACE appears to be
more effective in tumors which are highly vascu-
lar. Such observations have been reported by other
authors as well [18] We have found sarcomas and
carcinoid to be especially responsive but (as men-
tioned above) colon cancer to be less responsive to
TACE in keeping with being relatively less vascu-
lar. In the latter case, we are currently investigating
the efficacy of radioembolization (Yttrium-90, see
Chapter 11) for colorectal metastases to the liver,
and preliminary results appear to be more hopeful
than those previously collected for TACE.
10.5
Conclusion
With concerns regarding the survival benefits of
TACE for patients with inoperable hepatocellu-
lar carcinoma finally being put to rest [10,14], all
such patients should be considered for TACE. The
median survival of patients with inoperable HCC
is 4-7 months (which can be extended with maxi-
mal supportive care to approximately 10 months).
TACE prolongs median survival to more than two
years and, though rarely, converts some patients
into candidates for resection or transplantation.
Preliminary unpublished data from our institution
confirm a significant survival advantage of TACE
in patients with inoperable mass-forming cholan-
giocarcinoma. Nearly uniformly fatal, this disease
imparts a median survival of 4-8 months. Such
patients who have been treated with TACE (Protocol
identical to that of HCC) show an extended median
survival up to 20 months. The benefit of TACE on
patients with other histological types of inoperable
liver cancer has not been evaluated by prospective,
randomized trials. Given the low toxicity rate, lack
of alternatives and encouraging results for HCC and
CCC, it is reasonable to offer this treatment to such
patients. Indeed, no doing so would deprive them
of a reasonably expected survival benefit. Though
TACE can be applied to any morphologic type of
liver cancer (from solitary lesions to diffuse bilobar
disease), it must compete with percutaneous ablation
techniques for patients with up to three lesions each
less than 4 cm each. These percutaneous ablation
techniques (Table 10.1) under optimal conditions
provide benefits similar to surgical resection but
suffer from their own specific limitations. The most
commonly used percutaneous ablation techniques
areradiofrequencyablation(RFA) and alcohol injec-
tion (PAI). In experienced hands these techniques
have excellent results for up to three lesions with a
maximum diameter of 3-4 cm each. However, their
efficacy rapidly tapers for larger lesions. Table 10.7
shows the typical response/ recurrence rates of HCC
treated with RFA. Radioembolization with Yttrium-
90 microspheres is an alternative to TACE as an
intra-arterial treatment for unresectable HCC, CCC,
or secondary liver cancer, but efficacy data are more
scarce. TACE is an evolving technique and many
questions remain unanswered. For example, what
is the best chemotherapy "cocktail"? What TACE
protocol yields maximum survival benefit? Can it
be combined with systemic chemotherapy or other
abl.ition techniques? Will the addition of novel phar-
maceuticals (i.e. anti-angiogenesis drugs or drugs
that target calnbolic pathways uniquely) improve
survival? If so, what is the best regimen? We are
years and many studies away from answering these
questions, but the prospect of transforming inoper-
able liver cancer into a chronic disease managed by
a protocol of surveillance and regular ir
C. S. Georgiades and I.-I-. G esc Ivwind
is a matter of time. As treatment options change and
as more and more patients receive multiple differ-
ent treatments for their disease (i.e. RFA and TACE,
or systemic chemotherapy and TACE) we must also
evolve in how we view this disease. One of the salient
points is the del in it ion ol response, which according
to current criteria, depends on tumor size alone. The
advancement of imaging methods and their ability
to distinguish between necrosis and cystic change
versus viable tumor has rendered this view anti-
quated and inappropriate in our opinion. We believe
the most appropriate method to measure response
is to quantify the percent viable tumor remaining
after treatment. Currently the best way to achieve
this is by contrast-enhanced MRI or PET scanning
(the latter somewhat limited by its relatively lower
spatial resolution).
This final point is probably the most crucial.
Surgeons, hepatologists, oncologists, and interven-
tional and diagnostic radiologists bring their unique
and important input to the treatment planning for
these complex cases. Treatment planning should be
^ed after every intervention whether this is
Table 10.7. Radiofrequencv a o la r ion .■; an alternative I.
nique for the treatment of unresectable HCC
>5cm <25% >75%
As indie a fed above, resp> uise and ieau renre rates are inversely
proportional to lesion size. Up to three separate lesions of up
to 4 cm each can be treated with RFA, TACE, or both for that
matter with goo,", results. Lesions larger than 5 cm or more
than three lesions or any size should preferentially be treated
with TACE. Percutaneous eihj.no! o: noetic joid injection has
similar response rates to RFA and suffers from the same limi-
tations pertaining to lesion size and number
partial hepatectomy, TACE, systemic chemotherapy
or percutaneous ablation therapy, as the clinical
situation maychange for the better or worse. Amul-
tidisciplinary team approach to treating primary or
secondary liver cancer is a development that affords
such patients maximum benefit from what medicine
currently has to offer.
l.Achenbach T e; a I. (2002 i Chemoemoolizalion for primary
liver cancer. Eur 1 Surg Oncol 28:37-41
2. Adam R (20C_i ) Chemotherapy and surgery: new perspec-
tives on the treat mem of unresectable l:v T : meljsljses.Aiin
Oncol 14 [Suppl 2]:II13-I116
3.Camma C et al. (20C2i Trai'.sarteria! chemoembolizatiOEi
tor unresectable hepatocellular carcinoma: meta-analysis
of rjiiuomized controlled trials. 1-i.adiology 224:47-54
4.E1-Serag HB, Mason AC (2000) Risk factors for the rising
primary liver cancer m the Unite." States. Arch Intern Med
273227-3230
5.Feldman ED et al. (2004) Regional treatment options for
patients with ocular melanoma metastatic to the liver. Ann
Surg Oncol 11:290-297
6.Georgiades CS et al. (2001) New non-surgical therapies
in the treatment of hepatocellular carcinoma. Techn Vase
Intervent Radiol 4:193-199
7.HoganBAetal.i2002 ) Hep a tic metastases from an unknown
primary (UPN'i: survival, prognostic indicators and value
of extensive investigations. Clin Radiol 57:1073-1077
8. Inoue ¥ et al, i I L J L J4 i Hyper vase u la i liver metastases of gas-
tric cancer compJetely lespoitding to transcatheter oily che-
moemoolizjiien using erirubicin hydrocliioride, mitomycin
C and lipiodol. Gan To Kagaku Ryoho 21:1665-1667
9.Kjwji 5 et ill. ( ] 9Q2 ) Prospective jf;6 randomized clini-
cal trial for the treatment ol" hepaiocellular carcinoma -a
comparison of lipioclol-transcalheler arierial embolization
with and wiihoul adriamycin ■: firsr cooperative study!. "The
Cooperative study Group for Liver Cancer Treatment of
Japan. Cancer Chemother Pharmacol 31 [Suppl]:Sl-S6
lO.Kawai S et al. (1997) Prospe
of lipiodol-transcatheter arte:
treatment of hepatocellular carcinoma: a comparison iA
epirubicin and doxorubicin (second cooperative study).
The Cooperative Study Group for Liver Cancer Treatment
of Japan. Semin Oncol 24 [Suppl 6]:S6-38-S6-45
ll.Llovet JM et a 1. 12002 ) A r re rial embolization or chemoem-
bohzation versus symptomatic treatment in patients with
unresectao.e hepatocellular carcinoma: a randomised con-
trolled trial. Lancet 359:1734-1739
12.Nakahashi C et al. (2003) The impact of liver metastases
on mortality in patients initially diagnosed with locallv
advanced or resectable pancreatic cancer. Inl I Gastromtesl
Cancer 33:155-164
13.Sanz-Altamira PM et al. (1997) Selective chemoemboliza-
n on in the management of hepatic metastases in refractory
colorectal carcinoma: a phase II trial. Dis Colon Rectum
40:770-775
14. SeongJ et al(1999) Combined transcatheter arterial ch emo-
embolization and local radiotherapy .:■ I" unresectable hepaio-
cellular carcinoma. Int ] Radiat Oncol Biol Phys 43:393-397
15.Tanada M et al. (1996) Intrahepatic arterial infusion che-
molherapy tor tlir colon cancer patients with liver metasta-
ses - a comparison of arreria; embolization chemolherapv
versus continuous annual infusion chemotherapy, Gan To
Kagaku Ryoho 23:1440-1442
16.Tarazov PG (2000! Arterial chemoembolization for meia-
slatic co.orecta.l cancer in the aver. Vopr Cnlsol 4<y.:*<~. -56o
17. Wyld Let a 1.(2003) Prognostic factors for patients with hepatic
metastases from breast cancer. Br ] Cancer 89:284-290
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noma. Can I Gastroenterol 14:703-709
11 Radioactive Microspheres for the Treatment of HCC
s, Riad Salem and Jean-Fra
Introduction 141
Clinical Considerations 142
Patient Selection & Preparation 142
Technique 142
Calculation of the Total Dose To Be Delivered 142
Calculation of the Shunt-Ratio 143
Anatomical Considerations 143
"'■'Y-Microsphere Embolization 144
r'LUieiVi Recovery 145
Follow-up 147
Conclusion 147
References 1 48
11.1
Introduction
As in the case for transarterial chemoemboliza-
tion (TACE, Chapter 10}, radioembolization takes
advantage of the preferential hepatic arterial supply
of hepatocellular carcinoma (HCC) to deliver tar-
geted therapy to the tumor, relatively sparing the
liver parenchyma, which is mostly supported by the
portal venous system. Radioembolization is effected
via intra-arterial delivery of carrier spheres onto
which radioactive particles are attached. There are
two types of radioactive microspheres that can be
used in the treatment of primary (and metastatic
for that matter) liver disease. They both contain
Yttrium-90 ( 90 Y) as the active element but differ
in the type of carrier particle. The first is 9fh Y glass
C. S. Geohgtades MD, PhD
Assistant Professor of RjJiobgy and y.ngei v. Johns Hopkins
Medical Institutions, Blalock 545, 600 N. Wolfe Street, Balti-
more, MD 21287, USA
R. Salem, MD
Assistant Professoi .if Radiology jii; Oncology, Nor duves tern
Memorial Hospital. Department of Radiology, 676 North St.
Claire, Chicago, IL 6061 1, USA
J.-F. Geschwind.MD
Associate Professo: of Racoologv, ?;::gerv and Oncology, loans
Hopkins Medical Institutions, Blalock 545, 600 N. Wolfe Street,
Baltimore, MD, 21287, USA
microspheres (Theraspheres, MDS Nord ion, Ottawa,
Ontario, Canada), which are glass spheres with
a diameter of 25±10u.m, impregnated with 90 Y, a
radioactive element. Following intra-arterial infu-
sion, most Theraspheres embolize at the arteriole
level because of their relative size. S0 Y is a pure beta
emitter (937 KeV) that decays to Zirconium-90 with
a half-life of 64.2 h. The emitted electrons have an
average tissue penetration of 2.5 mm (effective max
10 mm) [1-5]. These physical properties stimulated
interest in the use of Theraspheres for the treatment
of HCC as well as metastatic liver lesions. Unlike
TACE, the effectiveness of '°Y-microsphere embo-
lization has not been established; however it is seen
as a viable alternative for patients whose hepatic
neoplasm does not respond to TACE. Histological
studies have shown that there is a disproportionate
accumulation of J Y-mk rospheres along the vascular
periphery of the hepatic tumor, with a relative con-
centration of 2.4 to 50 times more than in the normal
liver parenchyma [6,7]. Though the exact reason for
this is not understood (perhaps the altered blood
vessel flow and diameter that results from tumor
angiogenesis allows preferential embosphere flow),
this phenomenon can be used to deliver large doses
of radiation to the tumor, while relatively sparing the
normal liver. After lodgi iis iii ilie iisial arteriolar cir-
culation, the microsphere radiation has a maximum
effective tissue penetration of 10 mm, thereby spar-
ing the normal liver parenchyma beyond this limit.
Radiation essentially ceases 10 days after emboliza-
tion but even before that it poses no threat to others.
These advantages are exploited in this type of novel
treatment and the process is described below.
The second type of 90 Y carrier is resin-based
microspheres with a diameter of 29-35 urn and
are also infused via the appropriate hepatic artery
branch to provide selective internal radiation (SIR).
These SIR-Spheres (Sirtex, Medical Limited) have
an average activity of 40 Bq per sphere and can be
suspended in sterile water and contrast media to
the desired total activity [8, 9]. Since the radioactive
element is the same as that on glass microspheres,
the tissue penetration and decay characteristics are prolong survival, '"Y-microsphere (either glat
identical, as are patient selection, preparation, tech- resin-based) embolization is not considered a
nique, and recovery. five treatment option.
11.2
Clinical Considerations
11.3
Technique
11.2.1
Patient Selection & Preparation
Selection criteria are similar to those for TACE and
are listed in section 10.2.1 ("Chemoembolization
for Liver"). As with TACE, candidates must have
unresectable solid, primary or secondary hepatic
tumors. However, one crucial difference is the
degree of shunting between the hepatic artery and
hepatic vein. The detection of shunting during the
pre-TACE arteriogram needs to be addressed but
not necessarily quantified. Gelfoam embolization
and repeat arteriogram immediately or 7-14 days
later to document lack of visible shunting allows
for TACE to proceed. However, in the case of S0 Y-
microsphere embolization, shunting can result in
life-threatening complications and must be accu-
rately quantified. Radiation pneumonitis can result
from 90 Y-microsphere shunting to the lungs with
significant morbidity and possible mortality ensu-
ing, especially if the total lung dose approaches
30-50 Gy [3]. The method for quantifying shunting
is described in the following section.
Oktida stage and ECOG score should be obtained
prior to treatment, as severe liver dysfunction is
a contraindication to any form of hepatic artery
embolization including °"Y- microsphere emboliza-
tion. Laboratory values should be obtained prior
to embolization, including: a comprehensive meta-
bolic panel (NA, K, glucose, creatinine, BUN, total
bilirubin, AST, ALT, alkaline phosphatase, albumin,
total protein), hematology panel (hematocrit and/or
hemoglobin, white blood cell count, platelet count,
coagulation profile (INR, APTT) and tumor mark-
ers (i.e. AFP for HCC, CEA for colon cancer). These
values serve not only to ensure a safer procedure
(i.e. normal coagulation) but also to allow for proper
follow-up of hepatic and renal function and moni-
tor response (using tumor marker levels). A baseline
gadolinium-enhanced MRI with diffusion/perfu-
sion sequence should be obtained as part of staging,
for establishing response to treatment and for future
treatment planning. Based on current evidence, the
patients should be informed that though it may
Once the patient has been deemed a candidate for
M Y-microsphere embolization one has to calculate
two important values:
l.The total dose of radiation to be delivered which
is related to the efficacy of the treatment
2. The hepatic artery-to-vein shunt percentage,
which is related to the safety of the treatment.
11.3.1
Calculation of the Total Dose To Be Delivered
The total dose to be delivered depends not on the
tumor burden but on the total volume of the liver
(normal parenchyma plus tumor) to be embolized.
A CT or MRI should be obtained, based on which
the liver volume to be embolized is calculated. The
same MRI (which should include contrast-enhanced
and diffusion/perfusion sequences) can be used
as baseline to quantify the response to treatment.
Studies have shown that a total dose of 120-150 Gy
yields better results than lower doses [1,4,8]. The
total activity to be injected is calculated by:
DIGylxVlLI^GLOqj^
50Gy/Kg.GBqx[l-F]
where,
• A is the total activity to be injected (in gigabec-
querels)
• D is the desired dose to the volume of the liver to
be treated (in grays)
• V is the total liver volume to be treated (in liters)
• SGL is the specific gravity of the liver (1.03 kg/1)
• F is the percent hepatic artery-to-vein shunting,
• The factor 50 results from the fact that for soft
tissue (liver) the absorbed dose is 50 Gy per GBq
per Kg
Therasphere vials are supplied with predeter-
mined doses fractionated at 3, 5, 7, 10, 15 and 20 GBq,
therefore a tailored combination should be used for
each patient depending on the desire dose.
e Microspheres for the Treatment of HCC
In addition to the above dose calculation, in the ofthe liver/lungs a
case of resin-based Yttrium-90 treatment, some is calculated by
authors [10] calculate the tumor to normal liver
uptake ratio (T/N) and treat only if the T/N ratio is _ ALng
equal or greater than 2. ALng + ALi
? obtained. The shunt percentage
Where,
• At/An is the ratio of activity in the tumor divided
by the activity in nontumorous liver and can be
calculated from the images obtained for the cal-
culation ofthe shunt ration (see next section}
• Mt/Mn is the ratio ofthe tumor to nontumorous
liver volume calculated from CT or MR1 studies
11.3.2
Calculation ofthe Shunt-Ratio
From the above equation the only factor that needs
to be independently quantified is the percent hepatic
artery-to-vein shunting. This is accomplished by
performing a perfusion study ofthe liver with ?9 T-
m macroaggregated albumin ( w T-m MAA) parti-
cles, which are routinely used to perform a ventila-
tion/perfusion scan for the diagnosis of pulmonary
embolism. Commercially available .MAA particles
have a diameter of 50±13 fim (i.e. more than 90%
are within 10 and 90 u.m in diameter) [11]. Because
a slightly larger percentage of Jf Y- microspheres are
smaller than the diameter of the capillaries (com-
pared to MAA particles), the use of MAA to calcu-
late the shunt percentage tends to slightly under-
estimate the shunt. Therefore one should be rather
conservative in cases where the shunt percentage is
borderline and err on the side of safety. The initial
diagnostic hepatic arteriogram has a dual purpose:
first, to plan which hepatic artery branch will be
used to treat the tumor; second, to calculate the
shunt related to that vessel. Though most commonly
the main right or left hepatic artery is used, occa-
sionally a secondary branch may sut lice if it supplies
the entire tumor. Once the diagnostic catheter is
in the branch that will be used to deliver the 90 Y-
microspheres during the future treatment, 2-6 mCi
(75-220 MBq} of "T-m MAA is infused. Following
this, a perfusion study with antero-posterior planar
images is obtained whose field of view includes
the liver and chest. Steps 1-5 described below are
followed. After Step 5, the patient is taken to the
nuclear medicine department and the planar images
• S is the shunt percentage (percent of the total
activity that will be shunted to the lungs)
• ALng is the activity calculated over the lung fields,
• ALvr is the activity calculated over the liver field
Normal lungs can tolerate a total lung dose of
30 Gy [3], above which severe morbidity and possi-
bly mortality may result from radiation pneumoni-
tis. Thus, if for example, a total liver dose of 150 Gyis
desired the shunt should be less than approximately
20%. A safety factor can be introduced arbitrarily
to increase the safety margin. Figures 11.1 and
11.2 show two planar images of two patients who
underwent such a shunt study. The first patient was
deemed a candidate for radioembolization having
shown negligible shunting to the lungs. The second
patient showed significant shunting and would have
suffered complications related to radiation pneumo-
nitis had lie received raclioemholizafion.
11.3.3
Anatomical Considerations
Radioembolization takes advantage ofthe fact that,
while normal liver parenchyma receives most of its
Fig. 11.1. Planar gamma camera view of the liver and chest
following "T-m MAA infusion in the right hepatic artery of
a patient wirJi '.inresec table HCC. Activity is seen in the liver
(rtiTi'iri without any pulmonary activity. T lie shun: percentage
was calculated to be 2%i thus the patient is a candidate for
" u T-mic rosp her
w of the liver and chest fol-
lowing ""T-m MAA infusion in the hepatic artery of a patient
with unresectable HOI. significant I'almonaiv activity is seen
(ai'ivws) indicating a shunt. The liver activity is indicated by
an ijrroiWit'iii.i The shunt percentage was prohibitive; thus the
patient could not safely receive '"Y-microsp
blood supply (60%-80%) from the portal venous
system, malignant hepatic tumors, whether pri-
mary or metastatic, are nearly exclusively supplied
by branches of the hepatic artery. Cancer angio-
genesis (a.k.a. neovascularization) is a process by
which neoplastic cells recruit new blood vessels in
order to ensure adequate local oxygen tension. Due
to their relatively higher metabolic demands, cancer
cells "live" in a nearly constant state of hypoxia.
They respond by secreting chemotactic factors that
promote the formation of new blood vessels. Arterial
epithelial cells are much more responsive to these
factors, vchicb explains ivhv such malignant tumors
are supplied by the hepatic artery. Radioemboliza-
tion then selectively targets the tumor while liver
parenchyma is mostly (but not entirely) spared.
Accessory and/or replaced right or left hepatic
arteries are common (up to 20%-30%). In addition,
common origins of the left hepatic and left gastric as
well as right hepatic and right gastric arteries may
be added complicating factors. Such associations are
important insofar as they increase the risk of non-
target embolization, mainly the stomach, proximal
small bowel, and/or pancreas. Though self-limiting
gastritis, duodenitis, and pancreatitis have been
reported, no deaths have yet been documented from
nontarget embolization (excluding pneumonitis).
Irrespective of this, it is important to clearly delin-
eate vascular anatomy during the initial arterio-
gram in order to minimize morbidity. 1 f 90 Y-micro-
sphere treatment cannot be given safely due to left or
right gastric or gastroduodenal vascular anatomic
relationships, one should consider coil-embolizing
these vessels and then proceeding with '^-micro-
sphere embolization.
11.3.4
^-Microsphere Embolization
The treatment ['Ian having being decided upon, writ-
ten informed consent is obtained and the patient's
groin regions are prepared and draped in a sterile
fashion on the fluoroscopy table. Informed con-
sent should disclose the following risks: Injury to
blood vessels and/or organs, anaphylactic reaction
to contrast, worsening of renal function, infection,
worsening liver function or liver failure, and pos-
sibly death. One must document the pre-procedural
peripheral pulses and choose the femoral artery with
the strongest pulse for initial access. Sedation with
i.v. versed and fentanyl is used at our institution,
occasionally needing to be enhanced with Phener-
gan and/or Benadryl.
• Step 1-Obtaining vascular access. In most cases
access using an 18-g, single-wall needle followed
by an 0.035" guide wire is successful. In difficult
cases a 0.018" micropuncture set can be of help,
with or without the use of ultrasound guidance.
• Step 2- Maintaining access. A 5 Fr short vascular
sheath providing access in the right or left (stron-
gest pulse) common femoral artery is used at our
institution. A 4 Fr access set can be used in cases
where less traumatic arterial access is needed (i.e.
slightly abnormal coagulation profile), however
the smaller catheters may be a bit less control-
lable.
• Step 3-Abdominal portogram. A flush aortogram
via a multisideholed, pig-tailed catheter at the
level of the celiac artery will delineate the vascular
anatomy, tumor supply and provide a road-map
for more selective access. For the most part this
step can be skipped. In rare cases and after fail-
ing to easily cannulate the SMA and celiac access
with a selective catheter (see step 4), which may
suggest variant anatomy, one may fall back to it.
If performed, a 15 cc per s injection for a total of
50 cc is adequate.
• Step 4-Selective arteriograms. First, a 5 Fr cathe-
ter (Simmons 1 or Cobra glide catheters, Terumo)
is used to select the superior mesenteric artery
(SMA) and an arteriogram is performed using an
injection rate of 6 ccper sfor 3-4 s. Then the celiac
ldioactive Microspheres for I lie Treat nieni of HCC
artery is selected (again Simmon's 1 or Cobra
glide catheters, Terumo) and a selective arterio-
gram is performed with a similar injection rate as
above. In most cases the celiac axis arteriogram
will show the tumor blush to best advantage.
• Step 5-Selecting the final catheter position. A
glide wire 0.035" is advanced through the glide
catheter followed by the catheter itself. Though
one wants to be as selective as possible to avoid
treating normal liver, being too selective will
result in parts of the tumor not being treated. In
general, either the right or left main hepatic artery
is the optimal position for the treatment catheter.
In cases where there is tumor in both lobes, the
one showing more tumor blush on the diagnos-
tic arteriogram should be targeted. If the 5 Fr
glide catheter cannot be advanced to the desired
location because of unfavorable anatomy, a 3 Fr
mil 'roca truster (Renegade, Boston Scientific) over
an 0.018" guidewire (i.e. Transend, Boston Scien-
tific) can be used coaxially.
• Step 6a-If the objective is to calculate the future
dose to be delivered, then once the diagnostic
catheter is in the branch that will be used to
deliver the 90 Y-microspheres in the future, 2-
6mCi (75-220 MBq) of 9S T-m MAA is infused.
As described above, the patient is then taken to
the nuclear medicine department and the shunt
ratio is calculated (see section 11.3.2}.
• Step 6b-If the dose has been previously calculated
and the patient has been deemed a candidate for
radioembolization, then the dose is delivered
using the set-up shown in Figure 11.3. Extreme
care regarding the set-up (tubing connections,
stop-cock positions, etc) must be exercised as the
volume to be injected is small (a few milliliters)
and errors are usually irreversible.
• Step 7-The catheter and sheath are removed and
hemostasis is achieved with manual pressure or
the use of a closure device. Peripheral pulses are
rechecked and documented to make sure they
are stable. Though exceedingly rare, significant
changes may signify complications such as access
artery dissection or distal thrombosis.
The infusion set-up system is shown inFigure 11.3.
Careful set-up and inspection of the system is cru-
cial prior to infusion to avoid inadvertent spillage
or misadministration of the Theraspheres. A list of
basic materials needed is shown in Table 11.1.
Close coordination between the Interventional
Radiologist, Oncologist and Radiation Safety Offi-
cer is a must for an uneventful treatment. Even then,
Fig. 11.3. Schematic of the set-up for the treatment appara-
tus for w Y-microsphe:e embolization, i . syringe; 2, three-way
stop cock; 3, saline o;ig: 4. shir. Jed vi.il containing the UU Y-
niiiTO sphere solution; 5, need.es; r.-, ■:■-■.:: 1 1 ■.:■ iv infusion catheter;
7, excess ■"'Y-micro sphere solution collection via I. shielded
one must abide by the ALARA (As Low As Reason-
ably Achievable) principle to limit radiation expo-
sure. The process must be speedy without sacrificing
quality control, with proper shielding and radia-
tion dosimetry and utilizing the minimum number
of personnel possible. The infusion is given under
continuous fluoroscopic guidance to ensure proper
delivery. Once the total dose is given the catheter is
flushed with a few milliliters of saline to extrude any
particles remaining in it. The catheter and arterial
access sheath are removed, hemostasis is achieved
and the patient n
11.3.5
Patient Recovery
90 Y- microsphere embolization for liver tumors is
generally an outpatient procedure with minimal
complications. Patients are recovered and observed
for 4-6 h, essentially a post-arteriogram recovery.
Possible complications and mitigating interventions
are shown in Table 11.2. Mild pain and minimal
nausea are not uncommon and if controlled with
medication should not prevent the patient's dis-
charge. A small minority of patients will develop
post-embolization syndrome and require overnight
admission to control their pain, nausea and fever.
Even then, almost all will be discharged the next day.
The vast majority of patients report no symptoms
and return home the same day. A sample discharge
order sheet is shown in Table 11.3. They present no
ials needed for *Y-micro sphere embolizatio
Obtaining arterial ai
- g-single wail needle i Cook" i and 0.03a" Microp unci tire
guide -
(Bentson, Cook]
vascular sheath (Cordis")
5 Fr, pigtail- flush catheter :' Angjo J y na m -
V .i i :v. anting arterial ao
Pel i"o: :tt:ng abuonuna!
a or tog ram ics B ]
Performing selective SMA 5 Fr, hook, endhole glide catheter (Si
& celiac arteriogram mon's 1 , Terumo-' :
Selecting the final catheter Si m mon's 1 or Cobra glide catheter t
position 0.035" glide wire (Terumo)
The nticrocatheter (step a! :s used
2-6 mCi (75-220 MBq) of w T-m MAA
Yttrium-90 dose
i see rig. ] i .3 for additional su pokes i
Manual hemostasis
4Fr, 11 cm vascular sheath (Cordis;
4 Fr, pig tail- flush catheter i Angio cynt
Cobra (Terumo) or Michelson (Angiody-
3 Fr micro catheter (Renegade, Boston Sci-
entific') coaxially through the 5 Fr or 4 Fr
catheter above over a 0.018" wire (Transend,
Boston Scientific)
Closure dev
e to unfavorable
inly if die Simmons I glide canr.ol be advanced lo the desired location J
it the shunt ratio through the tumor to be treated must be calculated to avoid nontarget
:e performed during the patient's first visit followed by a plana i gamma-camera image that is used
to calculate (his ratio. 1: deemed a candidate for embolization, lhe patient returns a: a later lime and steps 1-5 and 6b-7 are
followed to perform me embolization. [Cook. Blooiuington : IN; Cora is. Cordis Corp., M:ami, l-L; Angio dynamics, Ciuee:tsbu:y.
NY; Terumo, Terumo Medical Corp., Somerset, \'i Boston Scientific, Boston, MA]
Table 11.2. Possible complications associated with J|, Y- microsphere emboliza
aia.j mii:g.Ui:'g . in er vent ions
Possible complications of radio-embolization Mitigating
Nontarget embolizatio
Turn
; Anti-ulcer, antacid med
Pre- and post-procedtit
Follow creatinine
Symptomatic support
hydra
Post- embolization syndrome
(Pain, fever, nausea/vomiting!
Racialion pneunr 'iiil:s
Such complications from radioembolization a
patients to have this procedure on mi outpatient basis, 1-iarely, treatmem may be complicated by
post-embolization syndrome and symptomatic supporl may be necessary. Nontarget embolization
can be all but eliminated by meiica.ous technique and pre-procedure planning
Admission-supportive
e exceedingly rare allowing the
rity of
Cable 11.3. Sample discharge h
» Discontinue all i.v. lines
» Discharge to home
• Medications: - Ciprofloxa
is for patients alter radioembokzatio
250mgp.o.bidx7days
- Oxycontin 10 mg p.o, q 12 h prn pain
- Oxycodone 5-10 mg p.o. q 4-6 h prn breakthrough a am
- Zofran 8 mg p.o. q 8 h prn nausea
• Instructions: - No straining, siai: ckmbing, or driving x 48 h
- If groin swelling or cruising, or fever, nausea/vomiting,
or worsening abdominal pain call ion call number)
• Diet: - As tolerated
• Follow-up: - Contrast- en it a need \' K 1 of liver and same day clinic aaaoinl mem want
(Interventional Radiologist! in 4-6 weeks
Send copy of discharge summary to ! referring physician's name)
" These are genera, guidelines. Spec
and clinical picture
c instructions shot
ailored to pat
e Microspheres for the Treatment of HCC
radiation risk to others and thus no special precau-
tions are required. Mild and self-limiting transami-
nase elevation is often seen but usually of no clinical
significance. Upon discharge, the patient is placed
on a 7-day oral antibiotic regimen (i.e. Ciprofloxacin
250 mgp.o. bid) and given PRN oral pain medication
for possible abdominal pain. One must remember
that occasionally, a patient who has been discharged
to home without complaints may develop pain,
nausea and/or fever within a few days afterwards.
Therefore the above med ical ions are recommended
for all patients regardless of symptomatology.
11.3.6
Follow-up
At approximately four to six weeks, the patient is
seen at the clinic and a contrast-enhanced, per-
fus ion/diffusion MRI is obtained. At that time,
one should address two issues. First, what is the
tumor's response to treatment and second, has the
patient's overall condition changed? The answers
to these questions will dictate whether the patient
still remains a candidate for embolization and if
so, should he or she continue with '"Y-microsphere
embolization or change the treatment plan. In estab-
lishing response to treatment, the pertinent factor is
the percent enhancement of the tumor in the MRI
scan, and not as classically thought, the size of the
tumor. Many times the tumor is killed entirely and
replaced by an indolent cyst or necrotic/fibrotic
tissue of similar size. Additionally, it is not uncom-
mon to see a lack of response after the first treatment
and a good response after the second or third treat-
ment, and thus at least two or three embolizations
are recommended before one decides on a change of
venue. ECOG score and laboratory values should be
retested to ensure that the patient remains a candi-
date for further embolization. Finally, re-evaluation
of the patient's clinical slams, including re-staging of
the disease if relevant changes are observed, is nec-
essary. Such re-evaluations may require the input of
surgery or hepatology in case adequate down-stag-
ing renders the patient a surgical candidate.
11.4
Conclusion
have been developed to attempt to improve survival
in these patients. Intra-arterial embolization with
90 Y- microspheres has shownpromise in early clinical
studies for the treatment of unresectable HCC. Such
patients are expected to live for about 5-7 months
with symptomatic treatment alone. Glass '^-micro-
sphere embolization has been shown to extend the
median survival to 12 months for Okuda stage II
disease and 23 months for Okuda stage I [4, 12]. Sig-
nificant turn or shrinkage has also been reported [6],
which again requires the constant re-evaluation of
patients in case surgical resection or transplantation
becomes an option. Additional, combination treat-
ments as well as treatment for colorectal metastatic
disease are beginning to appear, i.e. 90 Y-microsphere
embolization followed by hepatic arterial chemo-
therapy (HAC). The 1-, 2-, 3-, and 5-year survival
rates of patients treated with glass 90 Y-microsphere
embolization followed by HAC are reported at 72%,
39%, 17%, and 3.5%, versus 68%, 29%, 6.5%, and 0%
for HAC alone [13]. S0 Y-microsphere treatment has
the added advantage of very minimal toxicity/side
effects and quick recovery. Additionally, glass 90 Y-
microsphere embolization appears to yield similar
survival benefit to those of TACE for unresectable
HCC, with Geschwind et al. [2] reporting a 1-year
survival of about 63% for both and significantly
better than supportive treatment alone. Resin-
based 90 Y- microsphere embolization has also been
shown to provide a survival benefit, with Lau et
al. [10] reporting a median survival of 9.4 months
(1.8-46.4 months), with four of 71 patients becom-
ing resectable after treatment. Lau et al. [8] in
phase I &II clinical trials reported a median sur-
vival of 55.9 weeks for patients who received a tumor
dose > 120 Gy. Similarly, benefit has been shown for
patients with colorectal metastases treated with SIR
spheres. Gray et al. [14] and Blanchard et al. [15]
showed that about 501" of patients have exhibited
more than 50% shrinkage of the tumor with a con-
comitant decrease in CEA levels. Given the large
number of nonsurgical treatment options, patient
selection is of paramount importance. In this con-
text, 9fh Y- micro sphere embolization has a definite
niche. In the end, a multidisciplinary approach that
includes Interventional & Diagnostic Radiologists,
Oncologists, Hepatologisis, and Surgeons is a must,
in order to choose and tailor the optimum treat-
ment protocol and offer the patient the best hope
for extended survival.
With few if any surgical optic
i patients, many no
; for he pat
References
l.Carr IB (2004) Hepatic arterial M YI1rium glass mien
spheres liheraspherei for niiresectal-.i' ■U'p.. | :'.cllula- .;-
cinonjii: interim safety ;i:id survival dala vr. •.:.: patienls
Liver Transplant 10 [Supp! 1]:S107-SI 10
2.Geschwind JF et al. (2004) Yttrium-90 microspheres for ihe
treatment of hepatocellular carcinom.i ■. .ix:r:'L-nit:ril.-j;>
127:S194-S205
3. Salem R et al. (2002) Yttrium-90 microspheres: radiation
dierapy for unresectable liver cancer. . Vase nicrv sadiul
13:5223-S229
4. Salem R et al. (2004) Use of yttrium--}:: glass microspheres
: iheraspheiv; for ihe trearmem of in
lubr carcinoma in patient 1 vt-,\\: pof.n w - ih-i:— :h:siv I
Vase Interv Radiol 1 5:335- 34>
5.Sarfaraz M et al. (2003) Physical aspects of Yttrium 90
microsphere therapy for -e-resc'.ihk' "-ipst.. 1 :c*-::r'
Med Phys 30:199-203
i.CaoX et al.! 1000] Hepatic ndi.>e-n: - i: izaiiun wi:h y:tr:um
a giass microspheres for . '.-ic-' >■' prmary iver
cancer. Ch:n Med I 112:43:: *3i
7.Campr>ell AM el al. (2000) Analysis of the distribution
of intr; arterial microspheres in human liver lisihnvinf,
hepatii V'lrum ■*" mitr:isphere :fie:.ipy : hys Med iiiol
45:1023 I H33
8.Lau WY e: al. (1991) Treatment of inoperable hepato
cellula- carcinoma with mi rah era he arterial Yltr;jm 90
miir:i>phe:
I and II study. Br J Cancer 70:994-
999
9. Van Hazel Get al. (2004) Randomized phase 2 trial of SIR-
■•phiio p., » 1 1 u ; :i !"-.:■ n r : i c i 1 / J c n 1 1 ''V : :■ r i n chemotherapy versus
fiuorojra. . leucovorin oh emo therapy alone in advanced
colorectal cancer. ] Surg Oncol 88:78-85
1 0. 1 ju WY el si. (1 993) Selective internal radiation therapy for
-n-rcM';:.i:-.e hepatocellular carcinoma with intraarterial
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Phys 40:583 592
ll.HungJCel al. (2000) Evaluation of macro aggregated albu-
sizes for use .n pr.lmonary shunt sluoies. I Am
Pharm Assoc 40:46-51
12. Kent; Gil, Sundram FX (2003) Radionuclide therapy
'.■:• hepai.'.dlular ■.".'. re i noma. Ann Acad Med Singapore
32:ilR S24
I 3. Gray H el a:. (2001) Randomized trial of sir- spheres plus
Lhe::u::rn" ipy vs. chemotherapy alone tor treating ra:ie:i-s
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Oncol 12:17 1-1720
1 4. Gray K el ai. (1 992) Regression of liver metastases following
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210
12 Yttrium-90 Radioembolization for the Treatment
of Liver Metastases
Intiod^ciion 149
Pathophysiology and Therapeutic Principle
iIliiiio-.il C oir-i e'er Li tions 150
Anatomic and Technical Considerations 15
Ty-.crrS-hrre kiminislraiion 153
I ];usime!ry::ir TheraSphere 153
'. Infusion Technique 154
S::< Sphere* Administration 154
. Dosimetry :'-r SIR-Spheres 154
'. Infusion Technique 155
Calculation of Lung Dose 155
Results 156
Clinical Experience, Response,
and S.rviva 156
S1K Spheres*; Clinical Experience, Response
and Survival 157
Complications 159
Conclusion 159
References 159
12.1
Introduction
The liver is the most frequent site of metastases, pri-
marily due to the spread of cancer cells through the
portal circulation. Approximately 60% of patients
diagnosed with colorectal carcinoma will eventually
experience liver disease as the predominant site. As
with hepatocellular carcinoma (HCC), surgical resec-
tion of colorectal metastases otters the only chance for
cure. However, this option is only available to a small
percentage of patients. Many patients with other pri-
maries such as breast, lung, and neuroendocrine will
develop liver metastases during the course of the dis-
R. Salem, MD, MBA
Assist.ui; Prolvssoi .if Ha; jo logy anc neology, Nor duves tern
Memorial Hospital. Pepniimcal of Radiology, 676 North St.
Claire, Chicago, IL 6061 1, USA
K.G.Thi;hston,MA
17 Bramble Lane, West Grove, PA 19390, USA
J.-F. Geschwind, MD
Associate Proles?.: 1 : of kLiciologv, ?;::geiv and 0:- oology, lohiis
Hopkins Medical Institutions, Blalock 545, 600 N. Wolfe Street,
Baltimore, MD 21287, USA
ease. Therefore, there is a need for novel liver-directed
treatments for patients with unresectable metastases to
the liver. Current therapies for the treatment of liver
metastases parallel those for HCC and include: hepatic
arterial infusion of chemotherapy (HAI), trans-arte-
rial chemoembolization <TAC!-J, radiofrequency abla-
tion (RFA), and combinations of these treatments.
These treatments have displayed some effectiveness
in prolonging lite lor patients with liver metastases, but
are often associated with toxicities such as abdominal
pain, fever, nausea, and vomiting.
Yttrium-90 ( 90 Y> microspheres (TheraSphere, MDS
Nordion, Ottawa, Canada and SIR-Spheres, Sirtex
Medical, Lake Forest, Illinois) represent an intra-
arterial therapy, infused via a catheter placed in the
hepatic arterial system. The microspheres are selec-
tively delivered to the tumor bed due to the hypervas-
cularity of tumor relative to normal liver parenchyma,
where they become entrapped in the arterioles feeding
the tumor. Since Jf| Y emits beta radiation with a maxi-
mum average penetration of approximately 1 cm, the
majority of the radiation effect is directed to tumor-
ous tissue while sparing normal liver parenchyma.
This results in a maximum tumor icidal effect, while
minimizing potential compromise to normal liver
function. The therapeutic benefit derived as a result
ot effecting tumor kill while sparing radiosensitive
normal tissue provides a significant treatment alter-
native for patients who have limited treatment options
available. TheraSphere was approved by the FDA for
unresectable hepatocellular carcinoma in December
1999 under a Humanitarian Device Exemption, while
SIR-Spheres was approved in March 2002 for colorec-
tal cancer metastatic to the liver in conjunction with
infusion of intra-hepatic floxuridine (FUDR).
Pathophysiology and Therapeutic Principle
The rationale for intraarterial delivery of m Y micro-
spheres for metastatic disease to the liver involves
anatomic and physiologic aspects of hepatic tumors
that can be exploited for the delivery of a therapeutic
agent. Hepatic tumors derive at least 90% of their
blood supply from the hepatic artery, while liver
parenchyma obtains between 70%-80% of its blood
supply from the portal vein [1-8]. This differential
pattern of vascular perfusion provides an intrin-
sic advantage for hepatic arterial regional therapies
delivered selectively to liver tumors. Additionally,
many liver tu mors, both primary and secondary, are
hypervascular relative to normal liver parenchyma
as determined by contrast angiography. Thus, selec-
tive arterial delivery, as practiced in hepatic arte-
rial chemotherapy and chemoembolization, delivers
therapeutic doses of radiation that are preferentially
retained in the liver tumor, theoretically sparing the
surrounding noi"imaliH.nanr liver tissue. It has been
shown, using hepatic arterial injection of radiola-
beled microspheres in experimental tumors, that
tumor microcirculatory blood vessel density is 3-4
times greater than that of surrounding liver paren-
chyma [9, 10]. In particular, single photon emission
computed tomography (SPECT) with hepatic arterial
injection of r " Ml 'Ti;-m;KToa.!i* recited albumin ( MA. A)
has been used to investigate the patterns of micro-
circulation in patients with liver tumors and con-
firm findings in experimental animal liver tumor
models [11]. The incorporation of an appropriate
therapeutic radioactive isotope into nondegradable
microspheres can potentially be utilized to capital-
ize upon the selective advantage afforded by hepatic
arterial administration and by the increased arte-
riolar density of malignant tissue within the liver to
deliver a highly localized dose of radiation directly
to the intrahepatic tumor(s). It has been known for
some time that it is possible to inject the liver and
other organs with doses of nondegradable (glass or
resin) microspheres without producing overt isch-
emic damage [1, 9, 12].
Radiation pneumonitis is a concern with hepatic-
directed radiation treatment. Previous preclinical
and clinical studies with ,0 Y microspheres demon-
strated that up to 30 Gy to the lungs could be tol-
erated with a single injection, and up to 50 Gy for
multiple injections [13]. For this reason, patients
with "Tc-MAA evidence of potential shunting to
the lungs leading to lung doses greater than 30 Gy
should not be treated. Similarly, any flow of m Y
microspheres to the gastrointestinal system that
cannot be corrected by percutaneous coil emboliza-
tion techniques, as predicted on ' 0m Tc-MAA, is con-
traindicated because of potential adverse gastroin-
testinal events.
12.3
Clinical Considerations
The selection process for patients undergoing radio-
embolization is multifactorial. Patients with meta-
static disease to the liver might have undergone one
or several courses of systemic chemotherapy, surgi-
cal resection, and/or radiolrecjuency ablation. Rel-
evant clinical history having an impact on the safety
and efficacy of radioembolization might include
surgicallyplaced intrahepatic chemotherapy pumps
(causing chemical vasculitis), the use of radiosensi-
tizers (such as capecitabine or irinotecan), as well
as treatment with groth factor inhibitors, such as
bevacizumab. These patients have image findings
of progressive liver-domman! meraslatie disease,
regardless of any therapeutic benefit afforded by
the aforementioned therapies.
For all patients, one of the most important fac-
tors in determining eligibility tor radioembolization
is ECOG performance status. Patients presenting
with clearly compromised functional status (ECOG
2-4; see Table 12.1) are at high risk for rapid onset
of liver failure and associated morbidity with treat-
ment. Notwithstanding this precaution, each patient
deserves individual consideration given the favor-
able toxicity profile of radioembolization; some
patients with limited ECOG performance may still
benefit from therapy.
Liver metastases present with relatively consis-
tent findings on MRI, CT, or ultrasound. If a mass is
identified, pathologic confirmation of malignancy
metastatic to the liver is necessary. If ultrasound is
the initial diagnostic modality, additional cross-sec-
tional imaging should be obtained. Triple-phase CT
is highly sensitive in detecting hepatic malignancies.
Since the majority of liver tumors are angiographi-
cally hypervascular, scanning in the early phases
likelihood of detection.
equivalent
K.;['j]-itsky
Table 12.1. ECOG performance st
ECOG Characteristics
Asymptomatic and fully active 100%
Symptomatic; fully ambulatory; 80%-90%
:es:iii"-ed in phy^icallv strenuous activity
symptomatic; ambulatory; ciipaL^e of 60%-70%
se[f-ca:e; mcie It.aii 5C?o of waking
hours are spent out of bed
symptomatic; limited self-care; 40%-50%
spends more than 50% of time in bed
Completely disabled; no self-care; 20%-30%
:'ro:idJe;\
Ylrn u :•'.-'''!'■ }\ .j J ioe:v. l -1 ■:■■. i z:i i ioj j :■:■: die Treiitme:'/ .:■[' Liver !Welji-;wvt:;
Later phase imaging is necessary to detect other less
vascular lesions, the degree of multifocality, and to
identify portal vein patency. MRI is also a sensitive
modality to identity and characterize lesions, given
specific attention to diffusion weighted imaging
sequences.
One of the most important clinical parameters
that must be assessed when treating patients with
radioembolization is the status of overall liver func-
tion. In the absence of biliary obstruction, drug tox-
icity (e.g., capecitabine) or metabolic abnormality
(e.g., Gilbert's syndrome}, it is extremely unusual
for patients with metastatic disease to the liver to
exhibit elevated liver functions. In particular, total
bilirubin is usually normal in this patient popula-
tion. In cases where total bilirubin is elevated and all
of the abovementioned factors have been excluded,
it is likely that tumor infiltration within the hepatic
parenchyma is the causative agent, thereby imply-
ing a grim prognosis for the patient. The decision to
treat such patients should be based on the thorough
assessment of the possibility of extending survival
or palliating pain.
The pretreatment evaluation of a patient with
metastatic disease to the liver should include:
1. History, physical examination, assessment of per-
formance status
2. Clinical laboratory tests (complete blood count
with differential, blood urea nitrogen, serum cre-
atinine, serum electrolytes, liver function, albu-
min, LDH, PT)
3. Chest X-ray, tumor marker assay (CEA, AFP)
4.CT/MRI scan of the abdomen and pelvis with
assessment of portal vein patency
Similar to hepatic artery chemoembolization,
patients with bilobar disease should be treated in
a lobar fashion at staged time intervals, usually
30-60 days following the first treatment. Patients'
eligibility for repeat radioembolization should be
evaluated following every treatment. Patients on
chemotherapy should have this therapy discontin-
ued twoweeks prior to radioembolization. Che-
motherapy may be restarted twoweeks following
li.ni i ■ ■ e i li !_■ ■.: I i :-■ ..■ r i . .n.
12.4
Anatomic and Technical Considerations
Although recent implementation of CT, MRI, and
ultrasound with 3-D reconstruction for the iden-
tification of first- and second-order variants have
proven effective for the identification of large vari-
ant mesenteric vessels, these techniques are not a
replacement for conventional angiography. During
the evaluation of the patient for radioemboliza-
tion, mesenteric angiography and ""' : Tc-MAA lung
shunting scan must be performed [14-16]. Com-
plications as a result of inadequate assessment for
radioembolization and nontarget embolization
include unplanned/unexpected necrosis in unde-
sirable arterial beds, such as the cystic artery, GI,
cutaneous and phrenic capillary beds [17-22],
All patients being evaluated for radioemboliza-
tion should have the following angiographic evalu-
ation [l-l]:
Abdominal aoitogram-injection ot 15--20 cc/sec
for a total of 30-40 cc. This allows for the assessment
of aortic tortuosity, mural atherosclerotic disease,
and facilitates proper visceral catheter selection.
Superior mesenteric angiogram-injection of 3-
4 cc/secfor30 cc. This allows assessment of any vari-
ant vessels to the liver (accessory or replaced right
hepatic), as well as visualization and identification
of a patent portal vein. This injection rate allows for
the opacification of the mesenteric system without
unnecessary reflux of contrast into the aorta.
1. Celiac angiogram- mi eel ion of 4 cc/sec for 12-15 cc.
This allows for the assessment of normal hepatic
branch anatomy, the presence of a replaced left
hepatic artery, or other variant arteries without
reflux of contrast into the aorta.
2. Selective left hepatic arteriogram-injection of 2 cc/
sec for 8 cc. In cases of normal anatomy, this allows
for the assessment of flow to segments 2, 3, 4A, and
4B. Special attention should be paid to the falci-
form, phrenic, right or accessory gastric arteries.
3. Selective right hepatic arteriogram-injection of
3 cc/sec for 12 cc. Normally, the right hepatic artery
provides flow to segments 1 (caudate lobe may have
other blood supply), 5, 6, 7, and 8. Particular atten-
tion should be paid to the supraduodenal, retro-
duodenal, retroportal and cystic arteries.
4. Selective gastroduodenal arteriogram-injection
of 2 cc/sec for 8-10 cc. The gastroduodenal artery
normally provides flow to the pancreas, stomach,
small bowel, and omentum. Attention should be
paid to the identification of an accessory right
hepatic artery feeding segment 6. The threshold
lor prophylactic embolization of this vessel during
radioembolization should be quite low. Two exam-
ples of prophylactic embolization in preparation
for radioembolization are demonstrated in Figures
12.1 and 12.2.
Fig. 1 2.1 a-c..^upi\;;Uiode:i;il,g.i si: ''duodena I. r.ghi gas:ric artery embo-
lization. ■> Initial common hepatic arteriogram rerea.ing ;i small vessel
artery arising kom -he rigi'.t hepatic ariery representing the supraduo-
denal i srfijighr [iiTii! )). Relative position cc I he gas^ro duodenal artery
is noted d'ani'il iimur). Right gastric artery .'.rises from die proper
hepatic artery i iWj.'/V unviviicrais). t> Hollowing complete em holizji ion
of i lie gasno-duodenal i \vli:h' iini-.;: ) and right gas- ric arteries. s : ..per-
selective catheterization o\ the supraduodenal artery {stmiglir iii'i'ou )
reveals dislrihuiion to the .:. u .:■ ■■:. e tin . branches Uun-iTii blink dn L nr!.
c Kmoolizaiion o: the supraduodenal was conipleieo {sti\uglit iin\-.'. )
along wi;h the CI 'A {:iinvd .ji ji- ul. as well as the right gastric artery
allowing for optimal deliverv to the liver. The vascular s'apply to the
liver tumors has been convened and simplified moi- two feed.ng vessels,
the right and left hepatic arteries. The patienl underwenl safe infusion
of Y90 microspheres.
As described above, in order to visualize
small vessels as well as vessels that may demon-
strate reversal of flow (e.g., result of flow shunt,
or sumping secondary to hypervascular tumor),
dedicated microcatheter injection with relatively
high rates (2-3cc/sec for 8-12cc) should be per-
formed. Without adequate contrast bolus, many
ancillary vessels (which have profound effect on
hemodynamics and directed therapy) may go
unnoticed, resulting in toxicities including post
embolization syndrome, distal embolization,
and/or end nontarget organ necrosis or ulcer-
ation. Although it may be argued that high injec-
tion rates may represent supraphysiologic flow
dynamics, the potential changes induced as a
result of regional therapy with i adioembolization
(spasm, ischemia, stasis, and vessel injury) may
result in altered physiologic states and thus reflux
into these vessels. Every attempt must be made to
avoid this scenario.
Arteriovenous connections responsible for radio-
active particle delivery from the liver to the lungs
arise from cancers rather than from normal liver.
Thus, in the presence of liver cancers (particularly
hepatocellular carcinoma], n significant amount of
W Y microspheres may shunt to the lungs. Hence,
during the angiographic evaluation of a patient for
M Y, 4-5 mCi of ?9l "Tc-MAA must be injected in the
vessel of interest, followed by imaging for lung shunt
fraction in Nuclear Medicine. Given that the likeli-
hood of shunting is low with metastatic disease, we
favor whole liver (i.e., proper hepatic) MAA injec-
tion in order to assess the entire liver at one time.
Lung shunt fraction (LSF) is defined as total lung
counts/( total lung counts + total abdomen counts).
The lung shunt fraction that is obtained must now
be factored into the dosimetry portion of the treat-
ment plan.
The technical aspects of radioembolization are
quite complex and should not be undertaken lightly.
Ylrn u :•'.-'''!'■ }\ .j J ioe:v. lt ■:■■. i Z:i i ioj j :■:■: :\w Treat me:'/ .:■[' liver \:elj:;j- : ir-;
Fig. 12.2a-c. GPA/right gastric, a Com it; on hepatLi: arteriogram demon-
s hyper vascular tumors in ;: patient '.undergoing fjdioeiiibolizalioii.
GDA (black arrowheads) and right gastric inline arrowhead) must be
embolized to prevent no:;-targe: administration, b Right gastric catheieriza-
tion (arrowhead) demonstrates lioiv aA'itg the lesser curve of the stomach.
c GDA (bliick arroiv) and right gastric i '.viiifa iin-flir! embolization permit-
iing safe Y a raoioembolization.
Furthermore, the delivery of TheraSphere and SIR-
Spheres are distinctly different. Unlike SIR-Spheres,
the embolic effects of the 20-40 micrometer Thera-
Sphere 90 Y particles are angiographically negligible.
As described in this chapter, unrecognized collat-
eral vessels with consequent infusion of radioactive
microspheres are certain to result in clinical toxicities
if proper angiographic techniques are not adopted
(see package insert TheraSphere"', SIR-Spheres' fl ).
These might include gastrointestinal ulceration,
pancreatitis, and skin irritation as well as other
nontarget radiation. For this reason, aggressive pro-
phylactic embolization of vessels prior to therapy is
highly recommended such that all hepatico-enteric
arterial communications are completely eliminated.
These vessels include the gastroduodenal, right gas-
tric, esophageal, accessory phrenic, and falciform as
well as variants arteries such as the supra/retroduo-
denal. At our institution, where over 400 radioem-
bolizations have been performed, we have found our
GI toxicity rate to be well below 1%. This is due to
our standard practice of: (a) aggressive prophylactic
embolization of GDA/right gastric and other vari-
ant vessels, (b) use of nonembolic TheraSpheres'* in
a lobar and segmental fashion, and (c) use of SIR-
Spheres' fl in a lobar, segmental, and dose-fraction-
ated method (several small doses rather than one
larger dose) without reaching n completely embolic
12.4.1
TheraSphere Administration
12.4.1.1
Dosimetryfor TheraSphere
As described in the product insert, TheraSpher
consists of insoluble glass microspheres wher
Yttrium-90 is an integral constituent of the glas:
The mean sphere diameter ranges from 20 to 30 pm.
Each milligram contains between 22,000 and 73,000
microspheres. TheraSphere is supplied in 0.05 ml
of sterile, pyrogen-free water contained in a 0.3-
ml vee-bottom vial secured within a 12-mm clear
acrylic vial shield. TheraSphere is available in six
activity sizes: 3 GBq (81 mCi), 5 GBq (135 mCi), 7 GBq
(189 mCi), 10 GBq (270 mCi), 15 GBq (405 mCi), and
20 GBq (540 mCi) [23]. The corresponding number
of microspheres per vial is 1.2, 2, 2.8, 4, 6, and 8
million, respectively. The activity per microsphere
is approximately 2500 Bq [24].
Assuming TheraSphere "°Y microspheres distrib-
ute in a uniform manner throughout the liver and
90 Y undergoes complete decay in situ, radioactivity
required to deliver the desired dose to the liver can
be calculated using the following formula [15]:
TheraSphere: A (GBq) = [D (Gy) x M (kg)] / 50
When lung shunt fraction (LSF) is taken into
account, the actual dose delivered to the target
volume becomes [15]:
D (Gy) = [A (GBq) x 50 x (1-LSF)] / M (kg)
A is the activity delivered to the liver, D is the
absorbed delivered dose to the target liver mass, M
is target liver mass. Liver volume (cc) is estimated
with CT, and then converted to mass using a conver-
sion factor of 1.03 kg/cc.
As an example, an authorized user wishes to treat
a patient with the following characteristics: target
volume 1000 cc (1.030 kg), desired dose 120 Gy,
LSF=5%.
guide, and a priming needle guide, all contained in
a Lucite shield. A MONARCH™ 25 cc syringe (Merit
Medical) is used to infuse saline containing the
TheraSphere 90 Y microspheres through a catheter
placed in the hepatic vasculature.
Once the catheter is in place and the authorized
user is ready for delivery, the catheter is connected to
the outlet tubing. Delivery of TheraSphere is accom-
plished by pressurizing the MONARCH syringe. For
3 French catheter systems, the infusion pressure
should range from 20 to 40 PSI, while for 5 French
systems, the infusion pressure should not usually
exceed 20 PSI. It is essential that, irrespective of
the infusion pressure utilized, pressure and flow of
microspheres closely mimic that observed angio-
graphieally with gentle, hand injection of contrast.
The authorized user should familiarize himself
with the actual flow dynamics of the vessel being
infused and use a correspondingly lowered infusion
pressure where necessary, such as might be seen in
patients with decreased cardiac output. Given the
small volume of microspheres contained in a given
activity of TheraSphere (typically 27-90 mg}, a low
volume of saline is required to infuse a vial of Thera-
Sphere; the majority of the microspheres are infused
once a few milliliters of saline are injected. Further-
more, given the low number of microspheres infused
with TheraSphere (typically 1.2-4.0 million), the
entire vascular bed is never saturated. Hence, live
fluoroscopic guidance while the infusion is occur-
ring is not necessary. A complete infusion usually
requires 20-40 cc.
Activity required = (120 x 1.030} / 50 = 2.47 GBq 12.4.2
SIR-Spheres Administration
The patient receives an infusion of2.47GBqto the
target volume. Given a 5% LSF, the actual delivered 12.4.2.1
dose was: Dosimetry for SIR-Spheres
D (Gy) = [2.47 x 50 x (1-0.05)] / 1.030 = 114 Gy
D (Gy) = 50 x (2.47 x 0.05} = 6 Gy
12.4.1.2
Infusion Technique
The TheraSphere Administration Set consists of one
inlet set, one outlet set, one empty vial, and two
interlocking units consisting of a positioning needle
As described in the product insert, SIR-Spheres*
consist of biocompatible resin-based microspheres
containing ,0 Y with a size between 20 and 40 microns
in diameter. SIR-Spheres' is a permanent implant
and is provided in a vial with water for injection.
Each vial contains 3 GBq of yttrium-90 (at the time
of calibration) in a total of 5 cc water for injection.
Each vial contains 40-80 million microspheres [25].
The corresponding activity per microsphere for SIR-
Spheres is much lower than that of TheraSphere (50
Bqvs. 2500 Bq respectively) [24].
Just as with TheraSphere, assuming SIR-Spheres
W Y microspheres distribute in a uniform r
Ylir.i: :•>'"' K .. k1 i '.■riv.L'v.iz.i; io;"; :"■:■■: die Trer.tme:'/ .:■[' liver !\ ! ^ l,i ;i.i - : t ;
throughout Che liver and undergo complete decay in Table 12.2. Radioactivity delivered to the liver with SIR-
situ, radioactivity delivered to the li
lated using one of two available methods:
The first method incorporates body surface area
and estimate of tumor burden as follows:
A (GBq} = BSA (m 2 ) - 0.2 + (% tumor involvement/ 100)
[26]
leu- Sphere;, based c-
>50%
<25 %
3.0 '.".Bo
2.5 GBq
2.0 GBq
where BSA is body surface area.
The second method is based on a broad estimate
of tumor burden as described in Table 12.2 [25]:
For either SIR-Spheres© dosimetry models, A
(GBq) is decreased depending on the extent of LSF
(<10% LSF no reduction, 1096-15% LSF-20% reduc-
tion, 15%-20% LSF-40% reduction, >20% LSF no
treatment).
As an example, an authorized user wishes to treat
a patient with the following characteristics: total
weight 91 kg, height 1.83 meters (6 ft}, target volume
1000 cc, tumor volume 300 cc, LSF=S%.
Using the first method, the formula for BSA as
described by Dubois and Dubois [27] is:
BSA = 0.20247 x height 0725 (m) x weight 0425 (kg)
Therefore,
A (GBq) = 2.13 - 0.2 + (30/100) = 2.23 GBq
would be required using the BSA formula.
Alternatively, given the tumor burden of 25%-
50%, the patient could be prescribed 2. 5 GBq in activ-
ity based on Table 12.2 [25]. Given the 5% LSF, no
reduction is activity would be required. It should be
noted that for SIR-Spheres, the dosimetry described
in the product insert is based on whole liver infu-
sion. If a lobar infusion is intended, the infused
activity should be calculated assuming whole liver
volume, and then "corrected" to the proportional
volume of the target lobe. For example, if the right
lobe is the target and represents 70% of the entire
liver volume, the calculated activity to be delivered
should be multiplied by 0.7.
12.4.1.2
infusion Technique
The SIR-Spheres administration set c
Perspex shield, the dose vial, inlet and o
with needles. Standard 10- or 20-c
syringes preloaded with sterile water s
nsists of a
itlet tubing
: injection
to infuse the microspheres into the delivery cath-
Given the larger number of microspheres (40-80
million) and lower activity of SIR-Spheres (50 Bqper
microsphere) compared to TheraSphere, the delivery
of SIR-Spheres is distinctly different than that for
TheraSphere. Once the catheter is in place and the
authorized user is ready for delivery, the catheter is
connected to the outlet tubing. Given the very large
number of SIR-Spheres microspheres required to
deliver the intended dose, it is not uncommon for the
entire vascular bed to become saturated with micro-
spheres and an embolic state to be reached. For this
reason, fluoroscopic guidance is essential during
the infusion. The technique of SIR-Spheres infusion
involves the alternating infusion of sterile water and
contrast, never allowing direct SIR-Spheres contact
with contrast. This allows the authorized user to
adequately monitor the injection and ensure that
vascular saturation has not been reached. In cases
where unrecognized vascular saturation occurs and
microsphere infusion continues, reflux of micro-
spheres and nontarget radiation become a distinct
possibility. The infusion is complete if either (1)
the entire intended dose has been infused without
reaching stasis, or (2) stasis has been reached and
only a portion of the dose has been infused. Given
the risk of reflux and nontarget radiation once stasis
has been reached, the continued infusion of SIR-
Spheres is not recommended.
12.4.3
Calculation of Lung Dose
Radiation pneumonitis is a concern with hepatic-
directed radiation treatment. Previous preclinical
and clinical studies with °°Y microspheres dem-
onstrated that up to 30 Gy to the lungs could be
tolerated with a single injection, and up to 50 Gy
for multiple injections [13]. For this reason, patients
with 9?m Tc-MAA evidence of potential pulmonary
shunting resulting in lung doses greater than 30 Gy
should not be treated.
The absorbed lung radiation dose is the total
cumulative dose of all treatments [28]):
Cumulative absorbed lung radiation dose =
50 x lungmassf A L *LSF L
where A; = activity infused, LSFi = lung shunt frac-
tion during infusion, n = number of infusions,
approximate vascular lung mass (for both lungs,
including blood) = 1 kg [29].
This dose should not exceed the limit of 30 Gy per
single infusion and 50 Gy cumulatively. In patients
who require more than two treatments to achieve
tumor coverage or in patients being retreated in the
same target volume after progression, repeat 99ln Tc-
MAA LSF should be performed before each treat-
ment and calculation of cumulative absorbed lung
radiation dose included from all previous treat-
12.5
Results
12.5.1
TheraSphere: Clinical Experience, Response,
and Survival
Andrews et al. [12] presented data on 24 patients
including 17 with colorectal metastases to the liver,
six with metastatic neuroendocrine tumors, and one
HCC patient. Imaging at week 16 indicated a partial
response in five patients, minimal response in four,
stable disease in seven, and progressive disease in
the remaining eight patients. Other than mild gas-
trointestinal symptoms in four patients (unrelated
to TheraSphere), no hematologic, hepatic, or pul-
monary toxicities were observed. The authors con-
sidered the hepatic tolerance to radiation delivered
by 90 Y to be excellent at doses of up to 150 Gyused in
the study. Herba and Thirlwell [30] performed a
prospective dose-escalation study with TheraSphere
starting at 50 Gy and escalating in 25 Gy increments
to 150 Gy. There were 37 patients with liver metas-
tases, 33 of whom had colorectal metastases to the
liver. The authors observed no major hematological
or pulmonary complications but did observe some
gastroduodenal ulceration, which occurred early in
their clinical experience with TheraSphere, due to
inadvertent deposition of spheres in the GI tract.
There was a beneficial response observed by CT
i where t
uld be resolved. Stabil:
22/30 patients (73%). Due to the small sample size
of the study, no statistically significant relationship
between dose and clinical or radiological beneficial
effects was observed. However, the authors con-
cluded that TheraSphere treatment was a feasible
and safe technique with beneficial effects. Wong
et al. [31] presented data on TheraSphere treatment
of eight patients with unresectable colorectal liver
metastases. Tumor response was evaluated using
imaging (CT/MRI) and metabolic evaluation via
l8 F-FDG-PET and serum CEA. Five of the eight
patients had an improvement in their tumor activ-
ity, as assessed by a decrease in 13 F-FDG-PET meta-
bolic activity and confirmed by parallel changes in
serum CEA. However, as observed in other stud-
ies, the use of imaging by CT/MRI illustrated that
only some of the tumors that responded by meta-
bolic criteria revealed a corresponding decrease in
size. This study suggested that using tumor size
as an indication of treatment response would lead
to an underestimate of the effect of TheraSphere.
The authors concluded that there was a significant
metabolic response to TheraSphere treatment in
patients with unresectable colorectal liver metas-
tases. This treatment appealed to provide signifi-
cant palliation for patients with otherwise incur-
able disease. In a subsequent study, Wong et al.
[32] presented data on TheraSphere treatment of
27 patients with metastatic colorectal cancer to the
liver. Tumor response was evaluated via la F-FDG-
PET and serum CEA. The study evaluated the use
of l8 F-FDG-PET to quantify the metabolic response
to treatment comparing visual estimates to stan-
dardized hepatic uptake values. Visual estimates
were graded as: progression, no change, mild,
moderate or dramatic improvement. Visual esti-
mates indicated 20 patients responded to treatment
while seven patients experienced progression or no
change in their disease. There was a significant cor-
relation (r=0.75, p<0.0001) between the response
group identified through visual estimation and
as determined by hepatic standardized uptake
values. There was no statistically significant cor-
relation observed with CEA values (p=0.13), which
was attributed to the effect of extrahepatic lesions.
The authors concluded that treatment significantly
reduced hepatic tumor metabolism and appeared
to be palliative in patients with unresectable liver
metastases.
Goin etal. [33] perloi med a dose-escalation study
withTheraSpherein43colorectalmetastasespatients.
The study assessed dose-related effects on survival.
.'.-'''0 Ajilioc'r.^TO.izLiiioij :■:■: ~.\w Treiitme; 1 ^ of Liv,
i 27 patients
tumor response and toxicity. There we
threatening or fatal toxicities. The medi;
was 408 (95% CI=316-565) days. Tumor response
was evaluated by decrease in tumor size assessed
by CT imaging. By these criteria, two patients had a
complete response, eight had a partial response, and
35 (81%) were at least stable. Higher doses were asso-
ciated with greater tumor response and increased
survival (p=0.05). In addition, tumor hypervascu-
larity (p=0.01), higher performance status [base-
line] (p=0.002) and less liver involvement(p=0.004)
were associated with enhanced response or survival.
Clinical toxicities included duodenal/gastric ulcers
in six patients (14%) that resolved with medical
management. These were most likely due to inad-
vertent deposition of microspheres into the GI tract
via unappreciated collateral vessels. Other related
complications included single
fever and fatigue. There was no do
toxicities observed in the study.
Salem et al. [34] presented da
with colorectal metastases treated with Thera-
Sphere. Patients who had life-threatening colorec-
tal metastases to the liver for whom other therapies
were judged to be inappropriate or had failed were
treated. The majority of patients entering the study
had extrahepatic lesions (85%), 89% of patients had
undergone prior systemic chemotherapy, 52% had
bilobar disease, and 22% had >25% of their liver
replaced by tumor. Patients underwent baseline CT
and 18 F-FDG-PET imaging and follow-up imaging
for determination of efficacy. Metabolic response
was also evaluated by CEA levels. Greater than
80% of patients displayed response to treatment
assessed by 18 F-FDG-PET. The response observed
via CT imaging was less dramatic but paralleled the
l8 F-FDG-PET results. Almost all (96%) of patients
showed stabilization or response by one of the two
imaging methods. There was an increase in survival
tor patients with <25% tumor repla
[95% CI=250-481] days) versus tl
(162 [CI=153-237], p=0.0001). The overall median
survival was 286 [CI=218-406] days, likely as a
result oi the prevalence of extra hepatic lesions in tile
majority of the patients (23/27). However, patients
with an ECOG of (n=17) had a median survival of
406 [CI=250-490] days. Treatments were well toler-
ated with most events being transient (mild fatigue
[n=13], nausea [n=4], and abdominal pain [n=5])
and resolving without medical intervention. Six
patients (22%) experienced non-treatment-related
ascites/pleural effusion or laboratory toxicities as a
consequence of liver failure in advanced-stage, met-
t (339
: with >25%
astatic disease. The response rate compared favor-
ably to hepatic arterial chemotherapy and fewer
complications were anticipated due to the relatively
simple procedure required and the minimal toxicity
associated with TheraSphere treatment. The authors
concluded that TheraSphere appeared to provide
therapeutic benefit with minimal toxicity inpatients
with progressive metastases following failure on
systemic chemotherapy. In an ongoing study at our
institution, a cohort of 65 patients with metastatic
disease to the liver troin diverse primaries including
colorectal, pancreatic, melanoma, lymphoma, blad-
der, breast, and neuroendocrine were treated with
TheraSphere. All patients were treated on an outpa-
tient basis. Tumor response rate using RECIST cri-
teria was approximately 35%, while the 18 FDG-PET
response rate was significantly higher. Response
rates were accentuated in those patients who under-
went systemic chemotherapy following a full course
of liver-directed therapy with TheraSphere.
12.5.2
SIR-Spheres ': Clinical Experience, Response,
and Survival
Gray et al. [35] published a phase III randomized
clinical trial of 74 patients conducted to assess
whether a single injection of 90 Y in combination
with intrahepatic FUDR could increase the tumor
response rate, time to disease progression in the
liver, and survival compared to FUDR alone. Treat-
ment-related toxicities or change in quality of life
were also examined. All patients had undergone
complete surgical resection of a primary adeno-
of the large bowel, and only those with
:table metastases limited to the liver and
lymph nodes in the porta hepatis were included in
the study. In addition, patients were required to
have a WHO performance status of 0-2, adequate
hematological and hepatic function, and not have
evidence of cirrhosis or ascites. Both treatment
arms received 12-day cycles of continuous infusion
floxuridine (FUDR) at 0.3 mg/kg of body wt/day
that were repeated at four weekly intervals, and
continued for 18 cycles (or until evidence of tumor
progression, extrahepatic metastases requiring a
systemic chemotherapy change, unacceptable tox-
icity, port failure, or at the patient's request). The
SIR-Spheres treatment arm also received a predeter-
mined quantity of 90 Y that varied (2 GBq, 2.5 GBq, or
3 GBq) depending on the size of the tumor. Yttrium-
90 microspheres were administered one time only,
within four weeks of insertion of the hepatic artery
access port. The mean S0 Y dose administered was
2.156 +/- 0.32 GBq. There was no difference between
the 90 Y arm and control arm in the mean chemo-
therapy dose (1,863 +/- 1,735 mg FUDR vs. 1,822
+/- 1,323 FUDR per patient) or the mean number
of cycles of chemotherapy (8.7 +/- 5.6 vs. 8.0 +/- 5.0
cycles per patient). Six of 34 patients (18%) in the
hepatic artery chemotherapy (H AC) arm had at least
a PR, while 16/36 patients (44%) in the HAC + SIRT
arm had at least a PR. (p = 0.01).
Stubbs et al. [36] published a clinical trial of 50
patients with extensive colorectal liver metastases
not suitable for either resection or cryotherapy. The
study compared experience with S0 Y alone (n = 7)
and in combination (n = 43) with fluorouracil (5-FU).
For all patients, 90 Y microspheres were administered
as a single treatment within 10 days of hepatic artery
port placement. The dose was titrated to the esti-
mated extent of d isease (< 25% liver replacement: 2
GBq, 25-50% liver replacement: 2.5 GBq, and > 50%
liver replacement: 3 GBq) and given over 10 minutes,
a few minutes after 50 meg angiotensin II. Forty-
three of the 50 enrolled patients also received 5-FU
given at the time of ,0 Y continuously over 4 days
(1 gm/day), every 4 weeks. Prior to administration
of ?0 Y, a Wm technetium-labeled macroaggregated
albumin ( ?9m Tc-MAA) test was conducted to discern
the percentage of lung shunting and assess the risk
of radiation pneumonitis. Acute pain and/or nausea
was experienced in 14 patients (28%) at the time of
administration of 90 Y, and was managed with nar-
cotics and antiemetics. Six patients (12%) developed
an acute duodenal ulcer within 2 months after m Y
therapy and the initial cycle of 5-FU that was due
to misperfusion of the duodenum by either 9ft Y, 5-
FU, or both. Antitumor effect was assessed by tumor
marker (CEA) and CT response. Median CEA levels
were reduced to 25% of baseline values atone month
post-treatment with 90 Y, and remained < 30% of
baseline when followed for 6 months. Median sur-
vival for all liver metastases patients from the time
of diagnosis was 14.5 months (range 1.9 to 91.4) and
from the time of treatment was 9.8 months (range
1.0 to 30.3).
Stubbs et al. [37] published on 38 patients with
extensive colorectal liver metastases who received
SIR-Spheres. Liver involvement was < 25% in 19
patients, 25%-50% in 9 and > 50% in 10. Patients
received 90 Y in the hepatic artery via an arterial port
and subsequent 4-weekly cycles of hepatic artery
chemotherapy with 5-fluorouracil. The treatments
were well tolerated, and no treatment-related mor-
tality was observed. Response to SIR-Spheres ther-
apy, as indicated by decreasing tumor markers and
serial 3-monthly CT scans were seen in over 90% of
patients. Estimated survival at 6, 12, and 18 months
was 70%, 46% and 46%, respectively, and was prin-
cipally determined by the development of extrahe-
patic metastases. The authors concluded that SIR-
Spheres was well tolerated in patients with extensive
colorectal liver metastases and achieved encour-
aging liver tumor responses, which are well main-
tained by hepatic artery chemotherapy.
Van Hazel et al. [26] published a randomized
clinical trial of 21 patients with untreated advanced
colorectal liver metastases (with or without extrahe-
patic metastases) that compared the response rate,
time to progressive disease, and toxicity of systemic
5-fluorouracil/leucovorin chemotherapy versus
5-fluorouracil/leucovorin plus a single adminis-
tration of °°Y. Systemic chemotherapy consisted of
425 mg/m 2 fluorouracil + 20 mg/m 2 leucovorin IV
bolus for 5 days, and repeated in 4 weekly cycles.
Mean SIR-Spheres activity infused was 2.25 GBq.
There were five cases of grade 3/4 toxicity follow-
ing FU/LV and 13 cases following combined SIRT +
FU/LV, which were primarily elevated liver function
tests. Tumor response rates using RECIST criteria
were 10/11 (91%) and 0/10 (0%) for the combined
chemotherapy/ S0 Y and chemotherapy only arms
respectively (p<0.001). The time to progression was
significantly greater in those receiving combination
therapy compared to the chemotherapy arm (18.6
vs. 3.6 months, p<0.0005). Survival was signifi-
cantly improved in the combination arm compared
to chemotherapy (29.4 vs. 12.8 months,p=0.02). The
authors concluded that a single administration of
,{I Y significantly increased both tumor response and
time to progressive disease when added to systemic
FU/LV chemotherapy, with acceptable toxicity.
Studies are now underway to assess the efficacy of
combining SIR-Spheres with oxaliplatin, irinotecan
and bevacizumab based therapies.
Rubin et al. [38] presented a case report of a
patient with metastatic breast cancer to the liver
treated with SIR-Spheres. The authors concluded
that using an integrative approach to cancer treat-
ment including SIR-Spheres was successful in pal-
liating a patient with metastatic breast cancer. Boan
et al. [39] presented data on a nine-patient cohort
with primary and metastatic disease to the liver
treated with SIR-Spheres. Although no response,
toxicity or long-term data was presented, the authors
concluded that SIR-Spheres was well-tolerated by all
patients and that further evaluation was underway.
.'.-'''0 Aadioeraae.izaiioij :■:■: die Treatment of Liv,
Coldwell et al. [40] presented an abstract
describing 84 patients receiving 127 infusions for
colorectal metastases to the liver. The target dose was
90 Gy to the tumor and 30 Gy to the normal paren-
chyma. Objective response rates were 35% by CT,
70% by CEA, and 90% by l8 FDG-PET. Mean follow-
up time was 12 months, with median survival not
having been reached at the time of presentation. No
life-threatening toxicities were noted. All patients
who exhibited fluoroscopic cessation of blood flow
(stasis) during 90 Y infusion experienced post-embo-
lization syndrome. The authors concluded that
radioembolization provides encouraging response
rates with an improvement in overall survival with
acceptable toxicity in the group of patients treated.
control the progression of radiation hepatitis. With
radioembolization, care must be taken to ensure
that the normal parenchyma is not receiving exces-
sive radiation to a level where radiation induced
liver disease might occur. Finally, it must be stated
that the true mechanism of radiation hepatitis from
radioembolization is nut currently understood. Any
evidenci ■' ■' ii ■■■ ■ . otitis (e.g. anicteric ascites,
elevated alkaline phosphatase, elevated transami-
nases [42] represents an extension of the knowledge
gained from external beam radiation.
12.7
Conclusion
12.6
Complications
The most common complications of radioemboli-
zation include nontarget radiation (GI ulceration,
pancreatitis), radiation pneumonitis, and radiation
induced liver disease (radiation hepatitis). The inci-
dence of nontarget radiation should be minimized
it the above-described technical principles are fol-
lowed, including aggressive embolization of collat-
eral vessels and the use of fluoroscopic guidance.
The risk of radiation pneumonitis is mitigated if
dosimetry planning incorporates the 30-Gy lung
limit. The last possible complication of radioem-
bolization is radiation hepatitis. This mechanism
involves the irradiation of normal parenchyma
beyond that which is tolerated. Ingold et al. [41]
published a landmark series on radiation hepatitis
in a cohort of patients treated with whole abdomen
external beam radiation for gynecologic malignan-
cies. The classical findings of anicteric ascites, ele-
vated alkaline phosphatase, thrombocytopenia, and
veno-occlusive disease occurred in those patients
receiving greater than 30 Gy to the liver. Although
the mechanism of selective "internal" microsphere
radioembolization is distinctly different than exter-
nal beam radiation, liver failure in this unique form
of radiation hepatitis is a possibility. When radio-
embolization with microspheres is undertaken, the
objective is to administer the microspheres to the
tumor without affecting the normal parenchyma.
However, if the normal parenchyma receives a
threshold dose above a yet undetermined amount for
this mode of therapy, irreversible liver failure will
invariably ensue. Systemic steroid treatment may
There is a significant body of evidence supporting
the safety and effectiveness of radioembolization in
the treatment of metastases to the liver. The afore-
mentioned studies representing the collective clini-
cal experience supporting the safety and therapeutic
benefit of TheraSphere and SIR-Spheres in patients
with metastatic disease to the liver suggest further
investigation for additional applications. Disease
states where further work should be initiated include
HCC (primary therapy, randomization against
TACE, bridge to transplantation, tumor downstag-
ing), colorectal (combination with radiosensitizers
[capecitabine, CPT-11] or newer agents [oxaliplatin,
bevacizumab, celuximab]). and metastatic neuroen-
docrine cancer to the liver. Furthermore, this tech-
nology appears to be ideal for extrahepatic applica-
tions, such as the treatment of renal cell carcinomas,
meningiomas, as well as other malignancies that
are readily accessible am;ioj;raphically. There is also
much to be gained from a more rigorous approach
to investigating patient selection criteria, presenta-
tion of disease, and optimal dosimetry to obtain the
desired therapeutic effect given these factors.
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13 Portal Vein Embolization
Alain J. Roche and Dominique Elia
Introduction 163
Phytopathology 163
Portal Blood and Liver Regeneration 163
Portal Vein Emboliz.it i on and Liver
Regeneration 164
1 Mechanisms Inducing Regr:'.era;ion After PVE 164
1 is Winnie E j u j" e l; s e Cone!a:ed to ¥:.w. iional
Increase? 1 64
IndicaliiT. 1 :. ' Portal Vein Embolization 164
Calculation . i FRL.'Totrd Etiitcriomu Liver Volume
Kami ifii
Hepatocollular Carcinoma 165
;:'::: jr'i; -..■.'linoma 155
l.iver Metastasis 155
utuel jiuIj nations 156
Anatomy 165
Technique 156
Personal Technique 165
Other Techniques 16S
.1 I Usui Embolization or Proximal Ligation? 16S
.3 Embolic Agents 169
Complications 169
Tolerance 169
Complications 170
Does PVE Accelerate Growth Rate of Liver
Metarnasesr 170
Results 171
Liver Hemodynamic Effects of Portal Vein
Embolization 171
Induced Hypertrophy, Delay to Surgery 171
Hvlv: ; ropery :n Paiienis w:t:'. LLodei -ying Liver
Disease 171
Is Hypertrophy Predictable? 172
Is Liver Failure After Surgery Predictable? 172
Long- term Rrsuks jnd Survival 172
Future Developments and Research 172
Conclusion 173
References 173
13.1
Introduction
One of the prerequisites tor partial hepatic resection
is the presence of enough remaining functional liver
parenchyma to avoid life-threatening postoperative
liver failure. Therefore, the possibilities of curative
resection of liver tumors are strongly dependent on
the volume of the future remnant liver (FRL). In clini-
cal practice, these possibilities are frequently limited
when an extended right hepatectomy is mandatory
since the lef t lobe is small, or when major liver surgery
is indicated in patients with impaired liver function,
whatever the cause (cirrhosis, cholestasis, noncir-
rhotic fibrous disease, or severe fatty steatosis). The
aim of portal vein embolization (PVE) is to selectively
induce hypertrophy of the FRL during the preopera-
tive period. This is achieved by embolization of the
intrahepatic portal branches of the future resected
liver, therefore leadinj', to distribution of the entire
portal blood flow, containing hepatotrophic factors,
exclusively towards the FRL. Lhis technique was first
applied for patients with hepatocellular carcinoma
[29] with the double goal to induce hypertrophy of the
FRL and to prevent retrograde intraportal tumor dis-
semination from the tumor lobe. Fewyears later, PVE
was proposed in patients with hilar cholanpo.arvi-
noma carcinoma who frequently require major hepa-
tectomy in relation to their tumor location [39], and
in patients with liver metastasis where PVE extends
the indications for curative surgery [■!?].
13.2
Physiopathology
13.2.1
A. J. Roche, MD
Head of I nter ven 1 1 om; I Radiology Sec
C-u stave Rotissy, 39 Rue Cunulle Pesr
Cedex, France
_ _ .,_ It nas been c
D. Elias, MD
Head of Digestive Surgery Section, Institut Gustave Roussy, 39 branch ligat
Rue Camiile Pesmoclins, 94800 Villejuif Cedex, France sponding lobe and hypertrophy of the contralateral
d for a long time that portal
shrinkage of the corre-
A. I. Roche and D.Elia:
one. Moreover, it is well known in clinical prac-
tice Chat liver trophicity closely depends on hepatic
portal blood perfusion. Liver atrophy after surgi-
cal or spontaneous portocaval shunting, hypertro-
phy of the remnant liver alter partial hepatectomy,
Spiegel lobe hypertrophy in Budd-Chiari disease
where the caudate lobe remains the only one to still
have hepatopetal portal blood flow, occlusion of
portal veins from cholangiocarcinoma giving rise
to hypertrophy of the unaffected lobe, are some
examples illustrating this very close relationship.
It was established along the seventies that portal
venous blood flow promoted hepatic cell regenera-
tion [8] and that blood arising from duodenopancre-
atic area had strong hepatotrophic properties [50].
Insulin and glucagon were then soon recognized
as growth -regulatory factors which, when infused
concomitantly, synergistically stimulated hepatic
regeneration. More recently, hepatocyte growth
factor (HGF) could be isolated in different labora-
tories and described to rise after partial hepatec-
tomy. Multiple other factors such as cytokines or
transforming growth factor-alpha (TGF-a), have
also been demonstrated to play a role in hepatic
regeneration.
13.2.2
Portal Vein Embolization and Liver
Regeneration
13.2.2.1
Mechanisms Inducing Regeneration After PVE
(Table 13.1)
Occlusion of portal branches of the liver paren-
chyma to be resected redistributes the totality
of its portal blood flow, and consequently all its
hepatotrophic contents, towards the FRL. This is
the basic rationale of the method that triggers off
regenerative activity of the nonembolized portion of
the liver. Moreover, PVE dilates the portal branches
in the FRL, exposing liver vasculature to stretch
stress which act as a trigger for IL-6 release from
endothelial cells and contribute to the activation
of regenerative cascade in the FRL [26]. Induction
of heat shock protein in the nonembolized lobe is
supposed to have similar effects [40]. PVE also acts
through two potentially complementary pathways
specifically related to embolization: ischemia and
inflammation. With most of the embolic agents,
PVE induces a mild ischemia: apoptosis or necrosis
of some hepatocytes, and intercellular disjunction.
These lesions lead liver cells of the embolized liver
to produce regenerating factors [35]. Moreover, the
injection of embolic material induces a foreign body
reaction and a cascade of inflammatory phenomena
with production of cytokines and liver growth fac-
tors by Kup tier 1 cells and yiamilocytes. This pathway
may be more or less predominant, depending on
the intensity of the inflammatory reaction induced
by the embolic agent used for PVE. Consequently,
embolic agents inducing a strong inflammatory
:h as cyanoacrylate or ethanol, should
hypertrophy than others.
13.2.2.2
fs Volume
Increase?
Correlated to Functional
Even if volume increase of the FRL after PVE was
demonstrated by all the first publications, it had
to be proved that it corresponded to a functional
increase. Nowadays it has been clearly demon-
strated by the mean of many different techniques
that volume increase did parallel function increase.
PVE produces a significant increase in bile volume
and biliary indocyanine green concentration in the
FRL [53]. Histology examination of FRL and assess-
ment of volumetric, cell kinetic and morphometric
parameters attributed to PVE a gain of functional
hepatocyte mass and early induction of hepatocyte
proliferation following hepatectomy [19]. Levels of
erythrocyte polyamine, that is known to be related
to liver regeneration, increase along the seven days
following PVE [52]. Hepatic energy charge levels in
the FRL remain comparable to that of normal liver
[9], hepatic plasma clearance of sorbitol and antipy-
rine were stable after PVE [48], while the percent-
age of FRL to total liver volume increased, thereby
demonstrating that the functional reserve of FRL
increased. Functional improvement after PVE has
also been demonstrated through evaluation of the
first-pass lidocaine extraction [51] and (99m)Tc-
galactosyl serum albumin scintigraphy [34].
13.3
Indications for Portal Vein Embolization
Limits for hepatic resections, and consequently for
PVE, depend on multiple factors. The age of the
patient is one of these: the younger the patient is,
the larger a resection is tolerated. Liver function
> : ::'iT;i. Veii: t.iuLx'lizniii.'--:''.
Table 13.1. Mechanisms involved in i'.v^ertiopiiy Hirer PVii. Cv:o/:nes .111.:. grown h f.iciors produced by the
embolized liver need recira.l.'.Uon to be eriecUve upon FRL.
PORTALVEIH EMBOLIZATION
is obviously a predominant factor for de
ing the limit for a safe resection. Bilirubin
indocyanine green clearance and presence or not
of a cirrhosis are widely used as parameters for
evaluating liver function before hepatic resection.
Liver function is considered as normal if there is
no jaundice and indocyanine green clearance at
15min is <10%. Presence of jaundice or ICG clear-
ance 10%-20% indicates mild liver dysfunction.ICG
clearance >20% indicates more severe compromised
liver, also meaning that PVE should not be followed
by dramatic increase in FRL volume. At last, it is the
FRL/Total functional liver ratio for a given patient
(with or without compromised liver tunction) that
determines possibilities for a safe and complete
resection. Depending on the authors, PVE is consid-
ered when this ratio is expected to be <25%-40% in
patients with normal liver function and <40%-50%
in patients with liver dysfunction [3, 12, 32].
13.3.1
Calculation of FRL/Total Functional Liver
Volume Ratio
Many studies have demonstrated that CT estima-
tions of liver volumes in vivo were correctly corre-
lated to real volumes despite partial volume effect,
respiratory phase, or inter- observer variations. It is
widely admitted that tumors do not contain func-
tional hepatocytes. Consequently, tumor volume
must be subtracted from that of liver. Peropera-
tive radio frequency ablation (RFA) has been widely
developed along the recent years. When RFA is
planified for treating a tumor located in the FRL
simultaneously to the hepatectomy, one should pay
attention to subtract the supposed volume of the
future RFA lesion (tumor volume + safety margin)
from the total FRL volume.
13.3.2
Hepatocellular Carcinoma
PVE was initially proposed in HCC at least for con-
trolling retrograde tumor thrombus invasion in the
portal vein [29], but today there is little evidence
to support this supposed interest of the technique.
On the contrary, some authors pointed out that the
compensatory increase in arterial flow in the embo-
lized lobe might accelerate the tumor growth [54].
Most of hepatocellular carcinomas occur in patients
with compromised liver. Thereby this dramatically
increases the risk of severe postoperative compli-
cations and limits the possibilities for major cura-
tive liver resections. Consequently, PVE is actually
proposed in selected cases to extend indications for
curative surgery and increase its safety. Apart from
increasing the FRL volume and tunction, minimiz-
ing the sudden increase in portal pressure at resec-
tion in these cirrhotic patients may also be an advan-
tage of preoperative PVE.
A. [. fvodie.iiid li. t.i;v;
13.3.3
Cholangiocarcinoma
Radical surgery of hilar cholangio
ally necessitates major liver resection, mainly an
extensive right hepatectomy. Such a major interven-
tion is frequently impeded by a too small left lobe,
which consequently indicates preoperative PVE.
Moreover, the patient frequently develops obstruc-
tive jatindice that may severely injured functionality
of the FRL. Preoperative PVE is performed in these
patients after biliary drainage of the FRL. Ideally
patients should undergo PVE only when decrease in
the serum bilirubin level is obtained, which facili-
tate hypertrophy of the nonembolized sector. On
the contrary, biliary drainage of the future resected
parenchyma should not be performed in the preop-
erative period to allow a more important shrinkage
of the embolized territory.
13.3.4
Liver Metastasis
Curative resection of liver metastases is mainly
performed in patients presenting with colorec-
tal primary cancer. Liver metastases are found in
40%-70% of patients with a colorectal cancer. In
about one third of cases, the liver is shown to be the
only site of cancer spread, even at autopsy. There
is no spontaneous long-term survival in untreated
patients, whose median survival time range from
6 to 18 months. Furthermore, liver involvement is
the most important factor associated with decreased
patient survival. However, at time of diagnosis, the
majority of patients present unresectable tumors,
and resection can be performed in <20% of all
patients with colorectal liver metastases. The main
limitation for resectability is the impossibility to be
curative while leaving a sufficient residual amount
of functional liver parenchyma. Consequently, pre-
operative PVE may dramatically improve the pos-
sibilities for a curative (RO) resection of liver metas-
tases by increasing the volume and the function of
the future remnant liver.
huge benign adenoma (personal data), or even for
allowing resection in primary sclerosing cholangitis
[43].
13.3.5
Other Indications
PVE has been reported prior to resection of mul-
tiple benign adenomas which dissemination in the
liver parenchyma impeded curative surgery [11],
13.4
Anatomy
A thorough knowledge of hepatic segmentation and
portal venous anatomy is essential before perform-
ing PVE. Variations frequently occur and must
be well known. One may remember that almost
all variations concern right branches, making left
branches remarkably constant in their disposition.
The most frequent variation is slipping from right
to let! ol segment V anil VIM branches, separalelv
or together. Therefore two main variations are fre-
quently encountered: (i) trifurcation of the portal
vein in left branch, segments V + V1II branch and
segments VI + VII branch, when the slipping is lim-
ited; (ii) bifurcation of the portal vein in a right vein
limited to segments VI + VII and leftvein giving also
rise to segments V+V1II branch, when the slipping
is complete. Segmental branches of the right liver
mayalso slip separately, but the most frequent varia-
tions concern segment VIII branch that may slip to
the left as well as to the right.
13.5
Technique
13.5.1
Personal Technique
The procedure maybe performed undei
sedation and analgesia but most of the teams prefer
general anesthesia that provides more comfort for
the patient as for the operator. When the goal of PVE
is occlusion of right branches, the preferred access
of the portal vein is mostly the anterior subxiphoid
left route that allows antegrade catheterization of
all right branches to be occluded and free flow
embolization, thereby providing safer maneuvers.
The puncture is achieved under sonographic guid-
ance with a 5F-needle catheter (Table 13.2). When
branches for segment IV have not to be occluded, the
entry point in portal veins may be the Reix recess.
If segment IV is concern by PVE, it is recommended
to enter the segment III branch, upstream from the
recess, to facilitate catheterization of segment IV
Portal Vein Embolizi
Table 13.2. Personal cookbook
!-.[' ,; i I'.'.Ci'r
Puncture: 5F-needle catheter, 27 cm (Cook)
Catheterization:
5F catheter from the needle catheter
Guide wire: Kayak 0.035 J glide wire (Boston Scientific)
Embolic agent:
Cyanoaci yli'.te: Hisioacryi, 0.5 ml vials (B. Brjun)
Lipiodol Ultrafluide, 10 ml (Guerbet)
Embolization technique:
Three-way stopcock resistant to Lipiodol (Cook)
isotonic glucose solution.
Two 1-ml syringes (Terumo)
20 ml syringe
Echotip needle, 18G,20cm (Allege
iirae catheter with on demand shaping of the tip
0.035 shapeable glide wire (Terumo)
Embogold (700-900 urn) (Biosphere Medica"'
branches. Retrograde catheterization of the portal
vein forperforming a portography is the first step of
the procedure in order to identify individual intra-
hepatic branches and anatomical variations. In all
patients with a known or suspected compromised
liver, the portal pressure must be measured prior to
embolization as it represents a prognostic param-
eter. Catheterization of every branch to be embo-
lized is then performed with the 5F catheter of the
needle catheter device, with the help of a J shaped
0.035 glide wire. In case of left approach and very
tightened portal bifurcation, catheterization of the
right portal vein may necessitate to extemporane-
ously shape the catheter tip. Depending on indi-
vidual anatomy, a 1-2 cm length and 30°-90° angu-
lated tip is then shaped under steam to make further
maneuvers easier. Every main trunk to be occluded
is selectively catheterized for performing a distal
and free flow embolization. The degree of selectivity
(sectorial, segmental, or subsegmental) before each
embolization depends on individual anatomy and
local hemodynamic. It is chosen for each vein to
ensure a stable selective positioning of the catheter,
providing best conditions for free flow embolization
and preventing from inadvertent reflux of embolic
material. Massive reflux of embolic agent in the FRL
would annihilate its hypertrophy, or induce almost
total portal occlusion and thereby fatal portal hyper-
tension when the rest of the portal vasculature has
already been totally embolized. Consequently, right
branches originating close to the portal bifurcation
should be hyperselectively catheterized. Caution
should also be exercised to avoid reflux into left lobe
veins when occluding veins in segment IV. Due to
this potential risk, segment IV portal veins should be
occluded first for added safety, and sometimes even
with particulate embolic agent instead of cyanoacry-
late. As many authors, we mostly perform emboliza-
tion with a mixture of cyanoacrylate and Lipiodol.
Safe use of this embolic agent necessitates following
a very strict technique but, to our point of view,
presents multiple advantages. It permits to achieve
complete and durable occlusion. Its radio-opacity
increases safety at time of embolization. Histoacryl
and Lipiodol are mixed in a ratio of 1 part of Histo-
acryl for 1 to 3 parts of Lipiodol, the more Lipiodol
in the mixture, the longer the polymerization time
of the glue. Consequently, it allows distal emboliza-
tion in every case since the polymerization time can
be adapted to individual and instant hemodynamic
variations. Furthermore, the cyanoacrylate induces
a very strong inflammatory reaction, involving ves-
sels as well as bile ducts, that is thought to increase
production of hepatotrophic factors. The mixture
(Histoacryl/Lipiodol ratio close to 1/2) is prepared
in an insulin syringe, immediately prior to the first
embolization. If needed during the procedure, it is
possible to increase the dilution by adding Lipiodol.
The mixture is pushed with isotonic glucose, follow-
ing the "sandwich technique": the volume of every
injection of mixture being lower than the catheter
content. This is repeated as many times as necessary
for obtaining a distal and complete occlusion. The
total dose of Histoacryl will be 1-3 cc, administered
in 4-6 successive injections of mixture. Catheter
occlusion along repetitive injections of glue is a
risk of this technique. Pushing the 0.035 glide wire
through the catheter still in position, immediately
after each injection of glue minimizes it. This cleans
the inner wall of the catheter from residual glue/Lip-
iodol mixture, and gently push it out in the embo-
lized vein under fluoroscopic control. The three-
way stopcock also needs to be cleared from residual
glue after each injection. Anyway, both three-way
stopcock and catheter must be exchanged in time
before occlusion, at least every 3-5 injections. A
A. [. Roche mid li. t.i;v;
control portography is performed at the end of the
procedure and postembolization portal pressure is
registered. In our experience, the transhepatic tract
does not need to be embolized.
13.5.2
Other Techniques
been successfully used in cases of impossibility to
perform the conventional transhepatic technique,
due to tumor interposition or severely impaired
hemostasis [46). The surgical transileocolic approach
needs laparotomy but for some authors allows tumor
extension to be better assessed preoperatively [21].
Nevertheless most of the surgeons actually prefer the
transhepatic approaches.
13.5.2.1
Approaches
13.5.2.2
Distal Embolization c
Prior to complex hepatectomiesPVE may c
and right portal branches. A right transhepatic access
may be then chosen, giving preference to entering a
vein not to be occluded (Fig. 13.1). Some authors advo-
cate a right transhepatic approach in all cases, using
double- or triple-lumen balloon catheters for embo-
lization [42], Recently, the transjugular approach has
1 Proximal Ligation?
Distal embolization is achieved with particulate
agents, cyanoacrylate or other liquid agents. Proxi-
mal ligation is surgically performed or may be
done percutaneously with steel coils or detachable
balloons. Considering that the intrahepatic portal
vasculature was classically considered as terminal
Fig.1J.1a d. PVE under right tr
Mich la) for inducing
<if!f;t!Vf hypertrophy of the posterior
:::!.mr, of (he liver prior to hepa-
Si'tMmy for metastases aiming to
--esi-vt' ;:n.( segments VI and VII
. icrylrite+Lipiod. 'I cast
L'i emoonzed branches is
pl'.in h.m :!>) :;:'d CT conlrcl prio
surgery (ar
Portal Vein Embolizi
type, interest of performing a distal embolization
rather than a proximal surgical ligation has been
contested. Therefore, nowadays there are strong
arguments for preferring a distal occlusion. The
efficacy of PVE vs. right portal vein ligation before
extended right hepatectomy has been recently dem-
onstrated [6]. The increase in FRL volume was sig-
nificantly higher with PVE (188 +/- 81 ml vs. 123
+/- 58 ml; £=0.012). A strictly proximal occlusion
allows distal reentry through the intra -parenchyma-
tous vascular shunts opening [57]. After having con-
trolled patients with a previous proximal ligation we
also encountered antegrade porto-portal collateral
circulation bypassing the ligation and supposed to
be parabiliary veins homologue to the parabiliary
arteries well known to play a predominant role in
the development of intrahepatic arterial collateral
circulation's. Lastly, in rare cases we encountered
macroscopic disial intra hepatic porlo-pornil anas-
tomosis (Fig. 13.2} that could also minimize the effi-
cacy of a too proximal occlusion in some patients.
13.5.2.3
Embolic Agents
Many embolic agents have been used and compared,
either in animal experiments or clinical use. There is
no definitive argument in the literature infavor of one
specific type of embolus, excepted that the embolic
agent must provide a distal occlusion (Table 13.3).
Among particulate and liquid embolus, the actual
tendency is to favor agents inducing complete, distal
and durable occlusion as well as a strong inflamma-
tory reaction. Most of teams actually seem to prefer
Histoacryl/Lipiodol mixture. Absolute ethanol has
also been experimentally assessed and clinically
used by several teams [49, 57, 58]. Fifteen to 65 ml
of ethanol had to be injected to induce an adequate
occlusion, either in right portal vein or at a segmen-
tal or subsegmental level. Technical easiness of its
use and efficacy to inducing hypertrophy are clear
advantages of ethanol. On the opposite, its clinical
and hepatic biological tolerance appeared tobemuch
poorer than that of cyanoacrylate. Consequently,
one should be very careful in using this embolic
agent, especially in patients with compromised liver.
Recently, new agent have been studied in attempt to
benefit from ethanol advantages while limiting its
adverse effects [30] or using sclerosing agents com-
bined with gelatin sponge [25]. Coils do not induce
distal occlusion and are generally used combined
with a distal embolus [38] or in rare cases where
Fig. 13.2. ?-ponuinec-'.;s ii-iirLdiepjuc pixie-porta]
in the right liver \iii rv n-sj, demon si :Li:ed d : .j mg a direct tran-
shepatic po: togi jpj'.y under let': approach
Table 13.3. Com; 1 .; red ertk.'.cy of uifrereat : .,s : .:.'.l embojc jgems
Embolic agents
k'.d'.Kvd
.'.VLVl'MYohv
nE BAEREet al. [10]
Gelatin sponge
53%
i hv-.-ei iri.i-.--hv m 4 weeks)
Coils
44%
cvunoacrvlate
68%
Kaneko etal. [25]
ijehitin sponge
21.9%
(hvpertrophv ai 1 weeks)
Fibrin glue
13.5%
cynnoa cry late
25.0%
an efficient and safe occlusion is not feasible with
cyanoacrylate or particulate embolus. Particulate
calibrated agents may also be used: polyvinyl alcohol
particles [7] or Embospheres (personal data).
13.6
Complications
13.6.1
Tolerance
Clinical tolerance is generally excellent with only
mild abdominal pain or discomfort and slight fever
which disappear in less than 3 days. A flush syn-
drome may occur in the post embolization period in
patients with carcinoid primary, and should be sys-
tematically prevented. During the post PVE period,
A. J. Roche and ['. Hihs
prothrombin time remains above 70% of the base-
line value. Serum aspartate transaminase and ala-
nine transaminase slightly increase and may reach
a maximum value of threefold the normal value on
the first day post PVE, excepted when using ethanol
that induces a greater cytolysis. Alterations in the
total bilirubin level are insignificant. Normally, the
total duration of hospitalization for the procedure
does not exceed 3 days.
At histopathological study, there is no macro-
scopic difference between embolized and nonembo-
lized liver. Inpatients embolized with gelatin sponge,
small vessels remain patent even though the main
portal branches are obstructed. In patients emboli-
zed with Histoacryl (Fig. 13.3), portal vein walls are
damaged with their lumen filled with embolic mate-
rial and macrophage cells and periportal inflam-
matory reaction and fibrosis are constantly associ-
ated. A massive peribiliary fibrosis, as encountered
in sclerosing cholangitis, is also observed in most
of the cases treated with ivanoacrvlate. Specimens
contain very rare and small foci of necrotic tissue,
excepted for ethanol embolization where there are
more important.
13.6.2
Complications
In the literature from experienced teams, complica-
tions rate rarely exceed 1.5%, without any reported
mortality. Main reported complications include
pneumothorax, subcapsular hematoma, arterial
pseudoaneurysm a Her inadvertent arterial puncture
and portal vein thrombosis [31]. The risks are higher
in patients with portal hypertension and/or blood
Fig. 1 3.3. I.iver hi^top.'di'.OA'gy of [lie reseaed paieiiii'.vma
4 iveeks after postal embolization with Histoacryl. Portal
branch (P) filled with cyanoacrylate (C). Bile duct (B) pre-
senting a mosfivc pe:idik"ial lioiosis {arrows)
coagulation disorders. In patients who underwent a
duodenopancreatectomy and who chronically pres-
ent an infected biliary tree, the PVE can be done
without risk of hepatic abscess, contrarily to that
occurs after intra-arterial chemoembolization or
after radiofrequency ablation.
13.6.3
Does PVE Accelerate Growth Rate of Liver
Metastases?
It is well known that partial hepatectomy acceler-
ates local tumor growth [45]. Some of the cytokines
and growth factors involved in liver regeneration or
hypertrophy may also be involved in tumor burden.
For example, transforming growth factor- a is a
strong stimulator of liver regeneration but has also
been demonstrated to have stimulatory effects on
tumor growth in vitro [36]. Consequently, one could
suppose PVE to accelerate tumor growth of lesions
located in the FRL. Our group studied volumetry of
the FRL and that of liver metastases located in the
FRL in five cases [13]. Volumes measurement prior
to PVE and one month later showed that increase of
the normal liver varied to 59%-127%, compared with
60%-970% for the metastases. The ratio between the
growth rate of the left lobe and the liver metastases
varied from 1.0 to 15.6. However, the spontaneous
growth rate of metastases prior to PVE, that should
be subtracted to the total tumor growth to define the
exact potential enhancement by PVE, was unknown
in this study. More recently, Kokudo et al. demon-
strated an increase in proliferative activity of intrahe-
patic colorectal metastases inpatients who underwent
PVE compared with a control non-PVE group [33].
The Ki-67 labeling index of metastatic lesions was
significantly higher in the PVE group. Long-term sur-
vival was similar in the two groups but disease-free
survival was significantly poorer in the PVE group.
To overpass this potential adverse effect, some have
proposed a two-stage hepatectomy, PVE being per-
formed after a primary resection of metastases that
are present in the FRL [22], Radiofrequency ablation
of lesions located in the FRL, prior or simultaneously
to PVE, is also an alternative option (Fig. 13.4). To
conclude, complementary studies are still needed but
it is logical to consider that PVE accelerates tumor
growth in some patients and some tumors. However,
clinical experience demonstrates that this rare and
probably limited adverse effect remains negligible
compared to advantages of PVE in widely extending
indications for curative surgery.
Porro' Vein H 1 1 l _"> .l.;:i:i'-
Fig. 1 j.4a,b. PVE ui'.dcj lei": ironsliep.Ui,: rippii-ridi prior to iigli: l"iepotee:o:v.y extend e.". to segment IV for over metasioses from
ponoreiit!.: coremoid luiiior (iP.<fiT, : </ij. Perai to neons i :id:ol"requen.."Y o Not ion of o let": lobe single lesio:: (iinr:- 1 . ) is pel formed
along the sonic session. Control portogiophy lb) nflei PVH. the triple eooled KV needle oeing in plo:e {crossed arrow )
13.7
Results
13.7.1
Liver Hemodynamic Effects of Portal Vein
Embolization
When performed on a normal liver, right portal vein
embolization induces an immediate mild increase in
portal pressure, from 2 to 5 cm of saline. However,
some minutes or even seconds after embolization,
the portal pressure comes back to its initial value.
In patients with abnormal liver parenchyma, portal
pressure increase tends to be greater and more dura-
ble. Interestingly, in both cases, the portal pressure
registered immediately after PVE is similar to levels
registered after hepatectomy, and subsequently may
have a diagnostic interest in predicting the hemody-
namic surgical outcome [55].
13.7.2
Induced Hypertrophy, Delay to Surgery
Along the last 10-year period we have performed
PVE in 108 patients, before right hepatectomy in 43
cases, right extended hepatectomy in 58 cases and
more complex hepatectomy in 7 cases (6.4%). We
have reported a mean increase of 70% in the size of
the FRL and a ratio of FRL/Total liver that increased
by 12.4% and measured 32% four weeks after PVE
[12]. Main series report increases in volume of 30
to 42 % and FRL/Total liver ratio increases from
19%-36% to 31%-59%. Disparities maybe explained
by different delays before surgery (2-4 weeks), use
of diverse embolic agents and different proportion
of patients with compromised liver in the respective
studies [1, 21, 27, 28, 37, 58]. In animals, complete
hypertrophy of the contralateral hepatic lobe occurs
3-6 months after portal branch ligation. Hepatic
regeneration follows an exponential curve, with a
250% increase in the remnant volume during the
first week after resection of 80% of the liver. Delay
between PVE and surgery should be as short as pos-
sible to preclude any tumor growth. In our expe-
rience, all patients reached the critical FRL/Total
functional liver volume ratio of 25% after 4-5 weeks.
Consequently, as several other teams, we consider a
4-5 weeks delay before surgery to be a good com-
promise between hepatic hypertrophy and tumor
dissemination. Other teams consider the hypertro-
phy gain negligible after 2-3 weeks and prefer to
perform the resection earlier. Interest of PVE prior
to large resections was evaluated through retrospec-
tive [2, 16, 20] or prospective [15] comparisons with
non-PVE series. In all retrospective studies, FRL
were significantly smaller at presentation in PVE
group and thank to PVE were similar at surgery.
13.7.3
Hypertrophy in Patients with Underlying Liver
Disease
Almost all patients with normal liver experience
hypertrophy after PVE since only 86% develops
hypertrophy in patients with chronic liver disease
[15]. Furthermore, in most of the studies, hyper-
A. [. fvodie.iiid li. t.i;-<
trophy is milder and slower (35%-40% i
volume of the FRL at 1 month) than in normal liver.
In damaged liver due to viral hepatitis, increase in
volume of the FRL was 25% at 2 weeks, compared
with a 34% value in normal liver [56]. In HCC with
injured liver, Ji et al. recently reported FRL/Total
liver ratio increasing from 36% to 40.8% at 1 week
and 47.3% at 3 week [23]. More and more frequently,
major hepatectomy for metastases has to be done in
patients with liver fibrosis following long-term sys-
temic chemotherapy or intraarterial infusion. We
have reported that hypertrophy can also be achieved
in such cases of liver injury [12].
13.7.4
Is Hypertrophy Predictable?
Patients with diabetes mellitus have lower hyper-
trophy [41]. Imamura et al. showed that diabetes
mellitus, a high total bilirubin level at time of PVE
and being male each reduced the extent of hyper-
trophy in FRL and that cholestasis accelerated the
process of atrophy in the embolized lobe [21]. The
hypertrophy rate has a significant correlation with
the absolute value of portal blood flow velocity on
day 1 post PVE [18] and Doppler evaluation of left
portal branch velocity along the post PVE period
seems to easily predict the hypertrophy rate of the
nonembolized left lobe [17]. The parenchymal volu-
metric rate of the FRL before PVE in patients with
damaged liver parenchyma due to viral hepatitis,
and both this volumetric rate and prothrombin time
have been showed as independent parameters pre-
dicting the hypertrophic ratio of FRL after PVE [56].
Indocyanine green retention rate at 15min is an
adverse predicting factor for all patients and platelet
count is significantly correlated with the hypertro-
phic ratio in hepatocellular patients [24].
13.7.5
Is Liver Failure after Surgery Predictable?
Patient selection criteria for hepatectomy following
PVE are still under investigation. For Wakabayashi
et al. postoperative liver failure appears to be more
severe in patients having high portal pressure and
hypertrophy of the FRL lower than 20% [55]. In
another study, the same team founded that portal
pressure and serum level of hyaluronate measured
before and after PVE were the most useful param-
eters in prediction of the outcome of the following
hepatectomy [56]. The cut-off points of significance
for serum hyaluronate were 130 ng/ml and 160 ng/
ml before and after PVE respectively. Cut-off for
portal pressures was 16 cm and 25 cm of saline,
measured before and immediately after PVE respec-
tively. Consequently, lush imtialportalpressureand
important elevation after PVE both indicate limited
resection, and an initially elevated pressure should
be considered as a poor indication for PVE. Preop-
erative 99mTc-galactosyl serum albumin has been
reported as a useful tool for predicting residual liver
function before hepatectomy [44]. In patients who
needed major hepatectomy for biliary tract malig-
nancy and presenting with jaundice, skeletonization
of the hepatoduodenal ligament was significant Iv
correlated to postoperative hyperbilirubinemia,
even after PVE [16]. Anyway, in high risk group
of patients, PVE suppresses rise in total bilirubin
and thrombin-antithrombin complex, decreases
the incidence of postoperative complications and
reduces intensive care unit or total hospital stay after
hepatectomy [15, 16].
13.7.6
Long-term Results and Survival
In patients presenting hepatobiliary malignan-
cies without chronic liver disease, Abdalla et al.
reported equivalent median survival durations
when they underwent PVE or not prior to extended
hepatectomy (> or = 5 segments), respectively 40
and 52 months [2]. We have reported 5-year sur-
vival and 5-year disease-free survival of 34% and
24% respectively in t>0 patients who underwent PVE
for liver metastases, that was comparable with the
survival rates obtained after resection without PVE
[14]. Compared long-term results from the litera-
ture, in specific groups of patients presenting with
liver metastases from colorectal primary or with
hepatocellular carcinoma, are summarized in Table
13 4. All these studies demonstrated equivalence in
5-year survival and 5-year disease-free survival
between groups of patients preoperatively treated
by PVE or not (Table 13.4).
Future Developments and Research
Cyanoacrylate, the main efficient embolic agents for
PVE, necessitates sophisticated manipulations and
^orm' Vein Embolization
e 13.4. Long-term survival of pauenls vcith liver metastases from colorectal cancer or hepatocellular car>
.valence in long-ierm st.rvival rates between groups -A patients who underwent preoperative PVE ; PV'Ej
: ~i\\\ isncal
(NPVE)
Metastases from colorectal c,
Number of % of patients
resected resected after
patients PVE
Overall actuarial si
yfvalrate(%)
:LAYetal.[4] PVE 19
61
40
AZOULAY
et al [5]
PVE
89
67
44
NPVE 88
38
NPVE
60
S3
53
Hlia
i et al. [14] PVE 41
NPVE 357
87
37.3
38.1
Wakabay
s.shi et al
. [56] PVE
NPVE
72,2
72.2
80.2
39.9
44.1
very specific training for its safe use. Ethanol is also
efficient in inducing hypertrophy but carries out
poorer tolerance that limit its use at least in com-
promised liver. Therefore, researches for improving
embolic' agents for PVE are certainly still required.
Accessibility to a combined Angio-CT suite allows
realtime precise intrahepatic portal mapping during
the procedure and increases possibilities for on-
demand atypical and hyperselective PVE, adapted
to the most complex types of hepatectomies. A
FRL/Total functional liver ratio of more than 30% is
widely admitted as a requested condition for allow-
ing a safe hepatectomy in patients with normal liver.
However, curative resection is frequently discussed
inpatients presenting with an injured liver: liver cir-
rhosis and any type of liver fibrosis, previous intra-
arterial (or even systemic) long-term chemotherapy,
severe fatty steatosis, chronic hepatitis, or previous
hepatic resection. The cut-off of liver volume to be
preserved remains still unclear in these patients with
compromised liver and should be clarified through
prospective studies. Computer simulation of liver
resection or nnliotrequeikv ablution, for preopera-
tive assessment of volumes and function (possibly
based on the indocyanine green clearance) should
also be developed.
13.9
Conclusion
PVE is a safe technique allowing efficient preopera-
tive hypertrophy of the FRL in selected cases. It is
recommended to perform distal embolization rather
than proximal occlusion or ligation. Embolic agents
producing high local inflammatory reaction induce
greater hypertrophy than others do.
PVE neither improves nor worsens long-term prog-
nosis but it allows curative resection in patients that
otherwise are considered as unresectable. Nowadays,
it may be frequently combined with multiple other
efficient therapeutic modalities (systemic or intraar-
terial chemotherapy, chemoembolization, radiofre-
quency ablation) in order to lead more patients with
malignant liver tumor to radical surgery.
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14 Embolotherapy for
Neuroendocrine Tumor Hepatic Metastases
Kong Teng Tan and John R. Kachura
,.1 Introduction 177
-2 Pathophysiology a:o.l Clinical Considerali
,.3 Technique 179
,.3.1 Patient Selection 179
t.3.2 Emboliz.it ion Protocols ISO
7.3.3 Pre-Erabolization Preparation ISO
,.3.4 Embolization Technique (Table 1 4.2) J 8.
t.3.5 Post-Emboiization and Follow-up JS J
7.4 Results 184
7.5 Complications (Table 14.3) 1S4
7.5.1 Angiographic Complications 184
7.5.1.1 Nontarget Embolization 1S4
7.5.1.2 Embolization complications 1S5
7.6 Pitfalls 185
7.7 Conclusion 186
References 1S6
14.1
Introduction
Neuroendocrine tumors comprise an interesting
group of rare neoplasms, which are derived from
neuroendocrine cells interspersed within the gas-
trointestinal system and throughout the body. In
the gastrointestinal tract, they mainly manifest as
pancreatic islet-cell tumors and carcinoid tumors
which are essentially serotonin-secreting tumors
that originate from enterochromaffin cells. Due to
its rarity, the epidemiology of malignant
K. T. Tan, MB, BCh, FRCS, FRCR
Division of Vasai In: and Iroerveniional Radiology,
Pepailmen: of Medio:; I imaging, To.viiio General Hospital.
585 University Avenue, NCSB 1 C-563, Toronto, Ontario,
Canada M5G 2N2
J. R. Kachuha, MD, FRCPC
Division of Vasai I:;: and li^erveniional Radiology.
Deparlnien; of Medio a I imaging, Toronto General Hospital.
200 Elizabeth Street, Eaton South l-454d, Toronto, Ontario,
Canada M5G 2C4
docrine tumors was not well established until rela-
tively recently. A large population-based registry in
France documented incidences of 7.6 and 5.0 cases
per million population for men and women, respec-
tively, with increasing incidence over time for both
sexes [1]. All together, these tumors account for 1%
of all gastrointestinal tumors. The small bowel is the
most common primary site (40%), followed by the
large bowel (30%) and the pancreas (20%) [1],
Although these tumors are well known for pro-
ducing various hormonal syndromes, approxi-
mately half are nonfunctioning or do not produce
hormones ot clinical significance. In addition, these
tumors are often indolent, described by Moertel
[2] as "cancers in slow motion", with which patients
may live for many years. Indeed at the time of diag-
nosis, the duration ot symptoms attributable to the
tumor frequently exceeds several years. Neverthe-
less, patients with carcinoid tumor metastatic to the
liver have a median survival of only 3 years, with
at most 30% of them still alive 5 years after diag-
nosis [2,3]. Therefore, the index of suspicion must
be high in order to diagnose these tumors prior to
the development of metastases in a timely fashion.
When these tumors present clinically, the symptoms
are caused by either hormonal excess, local tumor
growth, or metastatic spread. Although surgical
extirpation remains the only curative modality, it
is feasible merely in patients presenting with local
disease, which accounts for <30% of all cases. On
;ral or lymph node metastases
l >70% of patients at first clini-
cal presentation, with liver metastases accounting
for 60% of all secondaries [1,4,5].
The main prognostic factors of these tumors are
the stage of disease at presentation, anatomical loca-
tion of tumor, histological subtype, and adequacy
of surgical resection [6-8]. Five-year survival of
patients with and without metastatic carcinoid
tumors are 0%-40% and 75%-99%, respectively
[2,3,9,10]. The corresponding figures for the second
most common gastrointestinal neuroendocrine
tumor, i.e. gastrinoma, are 20% and 65% [11].
the other hand, i
tlready are present ii
K. T. Tan and J.R.Kachura
14.2
Pathophysiology and Clinical
Considerations
Gastrointestinal neuroendocrine tumors often
develop extensive hepatic metastases that remain
clinically silent until the liver's metabolic capacity
is overtaken by the increasing serotonin and neu-
ropeptides produced by these tumors [12]. When
tumor burden overtakes hepatic metabolic func-
tion, the excess hormones are released into the sys-
temic circulation producing a variety of syndromes,
lest of which is the carcinoid syndrome,
:ed by flushing, diarrhea, cardiac val-
vular damage, broncho con strict ion, and pellagra.
Although these symptoms of are usually well-con-
trolled using somatostatin analogues (octreotide),
tolerance generally occurs which eventually leads to
a decrease and finally absence of therapeutic effec-
tiveness [13,14]. Furthermore, the use of octreotide
remains solelyas a palliative measure, as this therapy
has no significant effect on the neuropeptide pro-
duction nor reduces metastatic load [15,16]. Hence,
since the introduction of somatostatin analogues,
the commonest cause of death in these patients is
liver failure from tumor progression [17].
Liver metastases from neuroendocrine tumors
may be found synchronously with the primary
tumor, may occur following resection of a primary
tumor, or may occur in the absence of a detectable
primary tumor. Imaging modalities available for
the localization of both primary neuroendocrine
tumors and their metastases include ultrasonog-
raphy (US), computed tomogiaphv (CT), magnetic
resonance imaging (MRI), endoscopic ultrasonog-
raphy (EUS), scintigraphy, portal venous sampling,
and arteriography. Conventional cross sectional
imaging studies (US, CT, MRI) individually have
poor accuracy in locating the primary tumor, with
reported sensitivities of less than 30% [18-20]. When
combined with somatostatin receptor scintigraphy,
however, the detection rate improves significantly
to 70% [19]. For primary islet cell tumor detection,
EUS is the method of choice with reported sensitivi-
ties of 80-90% [21,22]. Although reported to have
good sensitivity, both portal venous sampling and
selective arteriography are invasive diagnostic tests.
As with the detection of primary tumors, the diag-
nosis of neuroendocrine tumor hepatic metastases
improves when somatostatin receptor scintigraphy
is added to US, CT or MRI, with the resultant sen-
sitivity exceeding 90% in comparison to 40%-50%
with cross sectional imaging alone [18-21]. In addi-
tion, scintigraphy is also the best screening test for
extrahepatic metastases, the presence of which has
significant impact on the treatment planning and
outcome [23].
Surgical management of metastatic neuroendo-
crine tumors remains a significant challenge. A few
authors have advocated hepatic resection for resect-
able hepatic metastases, with results supporting
palliation and prolonged survival in these patients
[2 I -33], Hov.'ever, most patients ( = 90 ! !.->) with meta-
static disease are unresectable at diagnosis; other
treatment options such as aggressive chemotherapy,
cytoreductive procedures, interferon, and symp-
tomatic control with conventional pharmacological
methods, all have disappointing results and cure is
rare [34-40].
Although neuroendocrine tumors vary in behav-
ior, these tumors share the clinical tendency to
metastasize diffusely to the liver and to be extremely
vascular [41]. Therefore, it seems logical to target
the liver with regional treatment when metastatic
neuroendocrine cancers have a substantial hepatic
component. The unique dual blood supply of the
liver allows interruption of the arterial supply with-
out major risk of hepatic infarction, as normal liver
parenchyma derives approximate!;-' T5% of its blood
supply and one-third of its oxygen supply from
the portal venous system. Tumors, however, derive
their blood supply entirely from the arterial system.
Some authors recommend bland liver embolization
whereas others suggest chemoembolization for neu-
roendocrine tumor hepatic metastases. In chemo-
embolization, an intra-arterial chemotherapeutic
agent is an added component to the embolization
procedure, with the premise that such an agent may
achieve a drug concentration greater than is pos-
sible using an intravenous route, with a long expo-
sure of the tumor to the drug [42] while attaining
low systemic toxicity. Furthermore, ischemia from
the embolization may render the tumor cells more
sensitive to the chemotherapeutic agent [43],
Detailed clinical management of patients with
liver metastases from neuroendocrine tumors is
beyond the scope of this chapter. A suggested treat-
ment algorithm is shown in Figure 14.1 [44]. Briefly,
candidates for treatment can be divided into three
groups: (1) those with surgically resectable liver
metastases with no extrahepatic disease, (2) those
with unresectable liver metastases with no extrahe-
patic disease, and (3) those with liver metastases as
well as extrahepatic disease [44]. Group 1 patients
could be offered surgicalmetastasectomy as this pro-
vides the potential for svmplonta tic improvement, as
EmbolothcTiipy for Ne^ro-endo-ciine Tuir.o: Hepatic Metastases
i \
.14.1. Treatment algorithm for patients ■
n 5 year survival from 20%-30%
without surgical excision to 50%-80% with resec-
tion [45,46]. In those patients with large liver metas-
tases, pre-resection hepatic artery embolization can
be performed to reduce tumor bulk and hence may
facilitate complete resection [47,48]. In addition,
pre-resection portal vein embolization of the lobe/
segments to be resected can be used to induce com-
pensatory hypertrophy and increase function of the
future liver remnant in patients with questionable
hepatic reserve. For group 2 and 3 patients, conven-
tional anti-hormonal pharmacological therapies are
still considered first line treatment although this is
being challenged by newer treatment alternatives.
Systemic chemotherapy such as streptozocin has
been used on its own or in combination with other
agents. The results are variable and often not long
lasting, however, with significant systemic toxicity
[39, 49]. Although early results with the therapeutic
use of 1131 metaiodobenzylguanidine (MIBG) are
encouraging, as a 5-year survival of 85% and symp-
tomatic relief in a majority of patients with meta-
static neuroendocrine malignancy can be achieved,
only approximated 511*0 ot patients are receptorpos-
itive for MIBG [50]. Moreover, a complete response
is rare and the long-term outcome and side effects
of MIBG are currently unknown [51-54]. Similarly,
intra- arterial infusion of Indiumlll pentetreotide
has been used in a small number of patients with
encouraging result [55]. Orthotopic liver transplant
for hepatic metastases of neuroendocrine tumor is
controversial. Early transplant aiming for cure has
been suggested for group 2 patient'. [44]. With the
perpetual donor organ shortage and variable results,
however, this approach requires further evaluation
[56-60].
Hepatic artery embolotherapy (with or without
chemotherapeutic agent) has been established as an
effective method in long-term control of hormonal
symptoms and pain, and in the reduction of tumor
growth in patients who are not suitable for surgi-
cal excision and refractory to medical therapy [48,
61-65]. Recently, Roche and coworkers proposed
the use of chemoembolization as the primary line
of treatment inpatients with unresectable neuroen-
docrine liver 1 metastases [<.>■!]. The authors reported
a 90% symptomatic and a 75% hormonal response
in comparison to the 30% -75% response rate with
somatostatin analogues, 43% objective tumor
reduction in comparison to 5%-15% with soma-
tostatin analogues, and a 5- and 10-year survival of
83% and 56%, respectively, which are considerably
better than the previously reported survival rates of
0%-40% inpatients who received only conventional
medical treatment [2,3,9,10].
14.3
Technique
14.3.1
Patient Selection
Eligibility requirements for hepatic artery embolo-
therapy for neuroendocrine tumor metastases are
summarized in Table 14.1. They include adequate
hepatic and renal function, acceptable coagulation
parameters, and hepatopedal portal venous flow.
While what constitutes an adequate amount of resid-
ual uninvolved liver is not clear, in most published
series 50% to 60% tumor replacement is considered
as the acceptable upper limit. It is well recognized
that over 75% tumor replacement is associated with
higher incidence of hepatic failure post emboliza-
tion [48]. In those patients with borderline liver
and/or renal function, superselective embolization
using smaller amounts of embolic agent and iodin-
ated contrast could be considered.
K.T. Tan and [. R. Kachui
14.3.2
Embolization Protocols
Unfortunately, due to the rarity of neuroendocrine
tumors, there is no consensus on the best embolo-
therapy protocol. A variety of methods have been
used, and no prospective comparative studies have
been conducted: (1) particles (bland) emboliza-
tion including polyvinyl alcohol (PVA}, tris-acryl
gelatin microspheres, or pledgets of absorbable
gelatin sponge, (2) chemoembolization using a
cytotoxic agent (such as doxorubicin, mitomycin
C, or cisplatin) and Lipiodol (ethiodized oil) with
or without a bland embolic agent, (3) cyanoacry-
late embolization, and, more recently, (4) selective
intra-arterial Indiumlll pentetreotide infusion
[27, 30, 42, 43, 47, 48, 55, 61-66]. Stokes and col-
leagues in 1993 suggested that chemoembolization
is associated with a shorter recovery period (pain
and liver enzyme elevations) in comparison to par-
ticle occlusion while producing similar efficacy
or response rate [67]. They compared 20 patients
treated with hepatic arterial chemoembolization
to their prior experience using gelatin sponge
powder alone for embolization ot metastatic endo-
crine tumors. Gelatin sponge powder, however, has
fallen out of favor as an embolic agent as it pen-
etrates distally and causes tissue necrosis. Also,
Brown and colleagues remind us that no study
has demonstrated superiority of adding either che-
motherapeutic agents or Lipiodol for the treatment
of neuroendocrine tumor hepatic metastases, and
that these agents may increase the risk of severe
complications [48]. Most published series reported
good symptomatic palliation, with response rates
ranging from 75% to 100%, following all of the
above embolization protocols. At our center, we
use PVA or tris-acryl gelatin microspheres for
embolotherapy of patients with neuroendocrine
tumor hepatic metastases.
For chemoembolization, the most widely used
agent is doxorubicin (50 ing/nr body surface area}
mixed with iodinated contrast agent and Lipiodol.
The amounts of contrast and Lipiodol used have
varied, ranging from 0-10 ml and 10-20 ml, respec-
tively. Following intra-arterial chemotherapeutic
injection, many routinely occlude the feeding artery
with particulate agents such as PVA or gelatin
sponge. In our experience, we have not been able to
predict the volume of Lipiodol and/or embolic mate-
rial that a right or left hepatic arterial system can
accommodate, based on tumor size, number, and
Inclusion criteria
Unresectable tumor
Patent portal venous system
Satisfactory live: function
Satisfactory renal function
Normal coagulation
Exclusion criteria
Occluded [lortal venous system
Hepatofugal portal venous flow
> 7?°s of hepatic parenci'.vma :eplaced by tumor
Hepatic encephalopathy
Poor liver function
Biliary obstruction
Renal failure
Uncorrectable coagulopathy
Life expectancy < 3 months
14.3.3
Pre-Embolization Preparation
All patients undergo analysis of baseline liver func-
tion, electrolytes, renal function, complete blood
count, and coagulation studies within 1-4 weeks
prior to the procedure. CT or MRI is performed
prior to treatment primarily for assessment of portal
vein patency and to document lesion size and dis-
tribution.
In order to decrease the risk of carcinoid crisis in
those patients with symptomatica!!)" active tumors,
150-500 micrograms of somatostatin may be given
the day before embolotherapy and continued for 3 to
5 days post-treatment [35]. Despite pre-medication,
however, carcinoid crisis can occur during the pro-
cedure, often manifested by hemodynamic instabil-
ity. For noncarcinoid or islet cell tumors, treatment
of underlying endocrinopathy must be initiated
before referral for embolotherapy. In our institution,
prophylactic intravenous antibiotic coverage with
cefazolin 1 g qSh and metronidazole 500 mg q8h is
used routinely during the inpatient stay. In some
centers, allopurinol and lactulose are also admin-
istered to prevent urate-induced renal failure and
post-embolization hepatic encephalopathy.
14.3.4
Embolization Technique (Table 14.2}
The patient is usually admitted the day before or on
the morning of the procedure after overnight fast-
Embolotherapy for Neuroendocrine Tumo: Hepatic Metastases
ing. Blood pressure, pulse, and oxygen saturation
are continuously monitored throughout the proce-
dure, and intravenous sedation (midazolam) and
analgesia (fentanyl) are administered as required.
Access to the common femoral artery is achieved
using Seldinger technique following the infiltration
of local anesthesia. A 4 or 5 French vascular sheath
is then inserted into the artery. Selective arteriogra-
phy of the celiac and superior mesenteric arteries is
performed to evaluate the anatomy of these vessels,
to assess portal venous flow, and to identify the
distribution of the metastases (Fig. 14.2). Once the
arterial anatomy is clearly understood, a catheter
is advanced selectively into the right or left hepatic
artery, depending upon which lobe has the great-
est tumor burden. If both lobes of the liver have
a similar metastatic load, then the hepatic artery
that is the easier to catheterize is embolized. A
4 French hydrophilic cobra catheter used with an
hydrophilic guidewire usually suffices. Embolic
and/or chemotherapeutic material is injected into
the selected hepatic artery. It is imperative that the
tip of the catheter is beyond any visceral branches,
such as gastric arteries, the cystic artery, and the
gastroduodenal artery, in order to minimize the
risk of nontarget embolization. Small vessels and
branches unable to be accessed with a standard
angiographic catheter may be selected with a
microcatheters (3 French or smaller}. To minimize
the risk of post-embolization hepatic failure, only
one lobe of the liver is treated on each occasion.
We use PVA particles or tris-acryl gelatin micro-
spheres > 100 u.m diameter, switching to larger par-
ticles (e.g. 300-500 |im) when arteriographic tumor
blush decreases, and terminating embolization
when there is flow stasis throughout the targeted
artery distribution. Although manufacturers have
Options for celi.'.c Littery I'.itd superior mesenteric artery
catheterization, in preferential order:
• 4 French Cobr.i 1 hydrophilic catheter and angled
hydrophilic guidewire
• 4 or 5 French Sos Omni catheter to engage the origin,
then exchange 'or :. 4 Hrencli Oc'fra 1 hydrophilic cath-
eter over a 03." straight Rentson wire or hydrophilic
• 4 or 5 French Simmons 1 or 2 catheter
• 4 French Simmon; 1 hycionhilic catheter
• Sos Omni or Simmons catheter to engage the celiac ori-
gin, and use microcalheter for st:pe:s elective catheter-
specific instructions for preparation of the particle
suspension, we find a 20-ml mixture of 50% full
strength nonionic contrast and 50% normal saline
satisfactory for any standard vial of embolic agent.
A 10-ml syringe is filled with this particle suspen-
sion, and is attached to an empty 10-ml syringe
and to the catheter by means of a three-way stop-
cock. By injecting the suspension from one syringe
to the other intermittently between embolization
injections into the catheter, a uniform suspension
of particles can be nicely maintained. Some advo-
cate the administration of lidocaine (10 mg bolus)
directly into the treated artery during emboliza-
tion, in an effort to reduce the pain experienced
during or after the procedure [68].
14.3.5
Post-Embolization and Follow-up
Following the embolo therapy, most patients will
have some degree of right upper quadrant pain,
nausea, vomiting, and low-grade pyrexia due to
post-embolization syndrome. The pain, nausea, and
vomiting usually resolve within 24 hours. Complete
blood counts, coagulation status, electrolytes, liver
and renal function tests are performed on daily
basis until the patient is discharged. Liver enzymes
typically become elevated immediately, peaking in
24-36 hours, and then decrease to pre- embolization
levels in less than one week. In those patients with
hormonally active tumors, production of 5-hyroxyin-
doleacetic acid, gastrin or glucagon diminishes con-
siderably (by 90%) within two weeks of treatment,
along with associated symptomatic relief [69].
Triphasic contrast-enhanced CT scans of the liver
areobtainedl day,l month, 3 months, 6 months, and
yearly after embolization, or as required, depend-
ing on the clinical status of the patient (Fig. 14.3).
The CT scans reveal changes in tumor morphology,
tumor size, overall liver size, and the development of
new lesions or metastases. Appropriate biochemical
tumor markers such as 5-hydroxymdoleacetic acid
for carcinoid tumor may be measured before and
after embolization at the similar intervals.
Most patients with neuroendocrine tumor liver
metastasis have extensive bilobar involvement. As
only one lobe is treated during each embolization
session, most patients require a minimum of two
treatment sessions in order to treat the entire liver,
depend ing on the hepatic arterial anatomy. An inter-
val of 4 to 6 weeks is recommended between treat-
How for liver function recovery.
K.T. Tan and [. R. Kachui
Fig.14.2a-h. Sixly-fou:-yeai-old female vcidi raa.dly progressing carcinoid liver metastases. The gastroduoaena! arteiy was
sargically ligaiea at I he nine of resection o'i ilie or unary tamo: at tbe gasno-dnodenal : unction 1 vear:; befoie. Arterial- phase
la} aa.d venoas-.'aase lb) CT anages :T iiver shove greater iv.eta slal. ■." barden in die len lobe. ^elecnve early (c,d) and delayed
(e,f) ane: iographic imaees of I - 1 ; heaanc arleiy :.I.HA:, berore (i.e.) and afier (d,f| eaacioazauon using [^ vials of 100-300 |jm
t:.s-aarvl £ea^:i:\ aa.crospaeres via a 4 r re nail '"ob:a II hvoroaiiuc catneter. Arrows de:'o:e stagnant coaarast coin inn i:; proximal
a spec I of eaaoonzed i.HA. Mos- of I lie ai.eaed contrast is see:' relieving int.:- ihe i iehl hepatio artery in (d J. Celiac a rtei iographic
images before (g| and after (hi LHA embolization
Emboli: 1 therapy tor Neuroendocrine Tumor Hepatic Metastases
Fig. l-!.3a--.l. !-if;v-si\-year-old fema.e with nonfunctioning rectal carcinoid luir.or me:asratic to live:, compl;'.:ned of upper
I'.bdonun.U pa :n and h. ::■ l" m ■. -::..i I symptoms, (a) l-'iv-embokz;'.! ion venous -phase '.IT .ma tie of the .iver shows ihe largest m eta si a sis
in the left lobe (arrow), (b) CT image with';;:: intii'.venous contrast injection, oblaineo immediately aftet i.HA emboliza:ion
: as:ng 4.5 viiils of tr:s-acryl gelatin microspheres, shows retained arteni'.llv :n:ected contrast within, the larges: me:as:asis (iin-i'ii'i.
(c) Venous-phase CT :mage 3 cavs pos:-emboliza:io:i shows decreased attenuation a:id a small amount of gas wiilun the large':
metastasis, consisteni w.th necrosis, id) Vrnoiis phase CT i::'.:'.ge a months posi-rmo-o-.izaii'.'n shows a sienir.cant decrease in
size of the largest metastasis, but growth -:A~ a new m curst, '.sis in Ihe caudate lobe (arrow)
K. T. Tan and J. R. Kachura
14.4
Results
At present, there is no conclusive data regarding
the effectiveness of embolotherapy for liver metas-
tasis from neuroendocrine tumor in comparison
to other methods of treatment due to various rea-
sons. It is an uncommon condition with a wide
spectrum of clinical presentations and severity in
addition to multiple treatment options. Hence, it
is highly unlikely that randomized trials will ever
be conducted to investigate this matter. All results
for embolotherapy published so far are case series
involving small numbers of subjects ranging from
14 to 41 patients with a wide range of disease sever-
ity. Despite this, allowing for different stages of dis-
ease and method of treatments, these series show
a good clinical response rate (reduction of symp-
toms, somatostatin requirement, tumor size) of
between 50 to 100%, with symptom-free intervals
of 5-10 months in 90%-100% of patients [43, 47, 48,
61-75]. Interestingly, the reported 5-year survival
of 53% to 83% post-embolotherapy is superior in
comparison to historical controls receiving medical
treatment alone (0%-40%) [2, 3, 9, 10]. However,
there is no definitive evidence that any particular
embolic agent is more superior to others.
Our center recently prospectively evaluated
11 patients with metastatic neuroendocrine tumors
treated with 20 hepatic artery embolizations using
tris-acryl gelatin microspheres for pain, hormonal
symptoms, and/or rapid tumor growth. On follow-
up CT scanning, 90% of lesions showed reduction in
vascularity suggesting tumor necrosis. All patients
had amelioration ol original pain and/or hormonal
symptoms (mean 31% decrease in pain score) lasting
3-15 months. There was one major complication:
encephalopathy for which no etiology was found and
which resulted in a prolonged hospital stay [70],
14.5.1
Angiographic Complications
Access site complications are unusual as a large-
diameter common femoral artery access is rarely
required for the embolization. Iatrogenic arterial
dissection occasionally occurs at the celiac artery
origin during difficult catheterization. In patients
with borderline hepatic or renal function, the risk
of contrast induced nephropathy and hepatorenal
syndrome can usually be prevented with optimal
hydration and by limiting the volume of liver embo-
lized.
14.5.1.1
Nontarget Embolization
Inadvertent extrahepatic deposition of embolic
material is relatively common. Although any non-
target embolization is undesirable and may cause
complications, the frequency of significant clini-
cal sequela is low [72]. Asymptomatic deposition of
embolic material may be seen in the lung, stomach,
pancreas, duodenum, gallbladder, diaphragm, and
Table 14.3. Complications of embolothenvv for neuroendo-
Angiographic complications
Access-related
Hisseclion / thrombo:;^
Distal embolization
Hemorrhage / hematoma ,' false aneui
Nerve damage
- Contrast media
- .Allergic / anaphylactoid
- Nephrotoxicity
- Catheter and general complications
- Air embolism .' :hromboembolism
Hraeturc <<f guide wire nl catheter
14.5
Complications (Table 14.3)
S'lXilurget emholi/aliun
(!hi:lt:cysliii>
I'an.Tc^lili 1
Splenic infarct
(iaslric or howo! :r!a:c:i
Serious complications following embolization of Pulmonary embolism
metastatic neuroendocrine tumor are uncommon
with careful patient selection, thorough pre-pro-
cedure preparation, and meticulous angiographic
technique [72]. Reported major complication rates
and death rates after embolotherapy for neuroen-
docrine tumor hepatic metastases range from 1% to
10%, and 0% to 3%, respectively.
Embolization compli<
Severe/prolonged post-
Carcinoid crisis
Anemi.'., net
:c!Xic Jgeiji )
- Liver abscess
- Liver failure
'botization syndrome
trc'penia, and throir.bocyropeaia ic
Embolotherapy for Neuroendoi
■r Hepatic Metastases
spleen. Some patients may develop significant com-
plications, however, from such deposition of embolic
material. Acalculous cholecystitis, gangrenous cho-
lecystitis, acute pancreatitis, and splenic infarction
have all been reported. Fortunately, most of these
complications can be treated conservatively and
they rarely require surgical interventions.
14.5.1.2
Embolizatioi
(implication:
Although the main objective of embolotherapy is to
cause tumor cell death, this by itself may have unde-
sirable effects. Post-embolization syndrome (pain,
nausea, vomiting, pyrexia, and malaise) practically
occur in all patients and can last for 1 to 2 weeks.
Anemia, neutropenia, and thrombocytopenia are
invariable if a cytotoxic agent is used. Secondary
infection of the necrotic liver/tumor can occur and
may lead to the formation of liver abscess (Fig. 14.4),
which may require percutaneous drainage. Previous
biliary tract surgery such as enterobiliary anasto-
mosis or sphincterotomy is associated with a greater
incidence of liver abscess, and this is likely due to
the colonization of the biliary tree by gut organisms
[76-78]. There is some evidence to suggest that bowel
preparation combined with tazobactam/piperacillin
given intravenously for 3 days reduces the incidence
of this complication in high risk patients [79].
Until the introduction of somatostatin analogues,
exacerbation of the symptoms of carcinoid or frank
isis was common with embolization of
carcinoid metastases. Now, with somatostatin ana-
logues used routinely for hormonally active tumors,
both during and after embolization, carcinoid crisis
occurs in only a small percentage of patients. Treat-
ment of these patients, who often have severe disease
of the pulmonary and tricuspid valves, is difficult
because there is little room for error when reducing
preload to treat pulmonary edema. Right atrial pres-
sure must be maintained to ensure adequate flow
through the diseased tricuspid valve. Maintenance
of right atrial pressure requires close collaboration
with an experienced anesthesiologist or cardiolo-
gist.
14.6
Pitfalls
There are many potential variations of the anat-
omy of the arterial supply to the liver. Scrupulous
attention to hepatic arterial anatomy, variants, and
nontarget branches is necessary to avoid potentially
devastating complications. In addition, hypervascu-
lar metastases can create a sump effect, reversing
the flow in the gastroduodenal artery (GDA). Thus
a superior mesenteric artery injection may fill the
hepatic artery via an enlarged GDA, which could be
mistaken for a replaced right hepatic. Furthermore,
a celiac injection in such a case may fail to opacify
the GDA because of the flow reversal and may give
the impression of an occluded GDA. After emboliza-
tion of the tumor, the flow will revert to antegrade
Fig. 14.4a,b. Fil'iy-fonr-year-old male wiri; me:as:auc neuroendocrine tumor of unknown r/riniary. (a) r':e- embolization venons-
phase CT image of die liver shows the largest me:as:asis in the left lobe i.-invirj. (IV) Venous- phase ;_T image of die liver
obtained 7 wks posi-e:rioojza:ior. of trie I..HA using r.- vials o: :ris-acry! gelatin. :v..-.":ospr.eres shows Ih.d ;h.e laities: meiasias.s
has decreased in size ,uv\ enhancement. bin contains a moderaie anion m o:' gas. The pa tie:'.: complained ...f :ever and r.oniii.ng,
which resolved with, an.iibiotic therapv. Tee -esion was not aspirated or drained, ttv sr.gges: perciiianeoi.s drainage only if a
palient becomes septic or if dieie is no response :o antibioses. Atrsivhc,;-.!; denote inleiva! growth of a right lobe i
K. T. Tan and ]. R. Kachura
in the GDA. Thus it is important to have the catheter
tip distal to the origin of the GDA to avoid nontarget
embolization.
Some advanced or superficial tumors mavpniasil-
ize arterial supply from thearteries of adjacent organs,
especially after multiple prior embolization proce-
dures. Such pniasitization may require embolization
of branches arising from such arteries as the right
renal, colonic, gastric, phrenic, internal thoracic, and
intercostal arteries. It is important to recognize that
not all such parasitized vessels can be safely treated
without risk to other important organs.
A patent portal venous system with hepatopedal
flow is essential to minimize the risk of possible
liver necrosis/failure post-embolization. In patients
with occluded or reversed flow (hepatofugal) portal
venous systems, embolization can still be performed
using a modified technique of superselective injec-
tion and reduced amounts of embolic material [71].
14.7
Conclusion
Current management strategies for neuroendocrine
tumor hepatic metastases have relied on data from
anecdotal evidence and retrospective studies involv-
ing small numbers of patients. It is unlikely that
this situation will change in the near future, since
prospective studies are difficult to perform in such
a relatively rare and biologically heterogeneous dis-
ease. Embolotherapy is a widely accepted method
of treatment for nonresectable hepatic metastases
from neuroendocrine tumors. Long-term palliation
of pain and hormonal symptoms is possible using
repeated treatment. Both bland hepatic artery embo-
lization and chemoembolization have been used,
and there is no conclusive data to indicate which
embolization method and which embolic agents are
most efficacious.
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15 Bone Metastases from Renal Cell Carcinoma:
Preoperative Embolization
Introduction 1S9
Clinical Features and Physiopathology 19L
Angiography and Embolization Technique
Ejid:-;:iNons 190
Preprocedural Preparation 191
Angiographic Technique 191
Embolization Technique 191
Results 193
Obliteration of Tumor Blush / Estimated
Blood Loss 193
O^eon;- Healing and Survival 196
Complications 196
Conclusion 198
References 199
15.1
Introduction
The American Cancer Society estimates that there
will be approximately 36,160 new cases of kidney and
other urinary carcinomas in the U.S. in 2005. Renal
a (RCC) is the most common type of
:er in adults, accounting for 70% of the
, approximately 25,312 new cases. Fur-
ince the 1970s, incidence rates for RCC
/erage of 2% per year, but
e appears to be leveling off [1,
e-tlurd of p.iiiei if s with KCC hnve metas-
tases at presentation [3], Eighty percent of patients
with RCC eventually have metastases, and nearly
one-half of these patients have metastases to the
bone [4-6]. However, more recent reports indicated
that with the significant improvement of imaging
techniques, such as ultrasonography, computerized
tomography (CT), magnetic resonance imaging
(MRI), and positron emission tomography (PET),
kidney ca
tumors, i
thermore :
recently th
2]. Up
S. Sun, MD
Associate Professor o:' Radiology, 1 ;ep-.n iintnt of Radiology.
University of Iowa, College of Medicine, 200 Hawkins Dr., 3955
JPP, Iowa City, IA 52242, USA
asymptomatic RCC is more frequently detected and
detected at lower stages ot disease, when tumors may
be resected with curative intent or when a metastatic
lesion is in the early stage [7, 8]. As a result, fewer
than 20% of patients with RCC have overt metastasis
at the initial presentation [7].
Treatments for RCC includes radiation therapy,
chemotherapy, and surgical intervention. RCC is
relatively radioresistant. The response rate to radia-
tion therapy is 50% at best, and symptomatic recur-
rences are common [4-9]. Despite extensive evalu-
ation of many different treatment modalities, RCC
remains highly resistance to systemic therapy, and
the median survival of RCC patients is ~8 months.
About 10% to 20% of patients exhibit complete or
partial response to interferon and/or interleukin-2
with/without chemotherapy or each therapy alone,
with a durable response of >2 years in 5% or less [3].
In patients with localized disease, surgical resec-
tion of the primary tumor remains the mainstay of
therapy [7, 8].
Although metastasis to the bone represents an
advanced stage of underlying disease, it may be asso-
ciated with relatively prolonged survival. However,
reports of survival conflict in a range of less than
15% to more than 50% [4, 10]. Therefore, indications
for surgical intervention and the appropriate extent
of surgery remain controversial. Wide excision of
metastatic lesions was advocated because of the unre-
sponsiveness of RCC to noninvasive measures, such
as chemotherapy and radiation therapy, and the pos-
sibility that survival may be relatively prolonged in
treated patients [10]. Existing reports on the surgical
management of metastatic RCC of bone have limited
value since they are based on only a small number of
patients or failed to mention the surgical technique
and its effect on local tumor control [10].
Most metastases from RCC are hypervascular
and tend to bleed massively during surgery [11].
Biopsies, open reductions, internal fixations, and
resections have been associated with an average
intraoperative blood loss of 1.5-3 L [12]. A blood loss
of 2000-18,500 ml (mean 6800 ml) was reported in
20 patients operated on during the pre- emboliza-
tion era [13]. Preoperative embolization of these
lesions appears to be a safe and effective technique
to decrease intraoperative blood loss and the dura-
tion of surgery, and thus reduce the surgical morbid-
ity/mortality:! nd hospital stay [11-20]. Preoperative
embolization has become a standard measure for
this type of patient before surgical intervention.
Clinical Features and Physic-pathology
Systemic symptoms may also occur, such ashypocal-
caemia. Occasionally, patients may have hyperten-
sion from the tumor affecting the rennin-angioten-
sin pathway. RCC metastases most commonly affect
the spine, proximal long bone, pelvis, ribs, sternum,
and skull [3, 22, 23]. Since the kidney is comprised
of mostly blood vessels, RCC is normally a hyper-
vascular tumor. RCC metastases usually mimic the
primary tumor in vascularity, being hypervascular
in 65%-75% of patients, and bleeding extensively
(even audibly) after a simple biopsy [3, 8].
Due to its visceral location and the existence of a
second functional kidney, RCC is characterized by a
lackof early warning signs, resulting in a high propor-
tion of patients with either locally advanced disease
or metastases already present at the time of diagnosis
[3, 21]. RCC metastases take place via the lymphatic
or venous routes. The lung parenchyma, bone, liver,
and brain are the most common sites of metastases
[3, 21, 22]. Although metastasis to the bone from RCC
ranks as approximately the sixth most common site,
compared to other tumors, this tumor has several
unique features that increase its significance: (1) the
metastases may occur many years (up to 10 years}
after the primary tumor has been treated surgically;
(2) the metastases may occur as a solitary lesion and
as such an en bloc surgical resection may render the
patient free of cancer and offer hope for a cure; (3)
even though the incidence of RCC is proportionally
small, the tumor has a high avidity for the skeletal
system and thus produces a relatively large number
of bone lesions; and (4) the bone lesions can be large,
with an average size of 7 cm in diameter, and have an
aggressive appearance [3, 19, 21, 22].
Pain is the most common presenting symptom.
Pathological fracture rarely occurs without a history
of a few weeks or months of increasingly severe pain.
Angiography and Embolization Technique
15.3.1
Indications
Due to the fact that most embolization procedures
were performed preoperatively, surgical indications
dictate the number and extent of the procedures.
Indications for surgery are divided into two groups
according to signs of mechanical skeletal failure
(Table 15.1). For patients who required amputa-
tion or wide radical resection due to massive tumor
extension to the soft tissue with invasion of the major
neurovascular bundle of the extremity, preoperative
embolization may not be indicated [10]. Similarly, for
patients with a small, easily accessed lesion or with an
angiography-proven very hypovascular tumor, pre-
operative embolization may not be necessary [18].
Otherwise, all other patients should undergo preop-
erative embolization with the intent to obliterate all
tumor feeders and decrease intraoperative blood loss.
General indications tor 1 Ira nscatheter embolization of
bone metastasis are listed in Table 15.2. Even though
listed, practically, the applications of this technique
in the indications other than preoperative emboliza-
Table 15.1. Indicator* for ■angeiy
Without mechanic;!' bone failure • Solitary bor
With mechanical bone failure
• Intractable pain
• Impending or pathologic:
Table 15.2. Indications for embolizatio
Preoperative embolization (72%)
Control of hemorrhage
Inhibition of tumor growth
Reducing viable minor volume to facil
.e Metastases from Keiul Cell Ciiiiaoau: Preoperative Emboliza
tion have been limited, with only sporadic reports ii
the literature [11-20].
15.3.2
Preprocedural Preparation
Due to the preoperative nature of the procedure, the
orthopedic surgeon should do a complete work-up
of the patient to rule out all potential major medical
contraindications for surgery. Interventional radiol-
ogists should review every document available and
focus on issues related to the embolization proce-
dure. One should perform and document findings
of physical examination in terms of the patient's
general condition, the status of affected limb, and
circulation of the extremities in order to set up a
baseline and compare with postembolization find-
ings later. For patients who have a history of contrast
allergy, premedication should be given according to
the institutional protocol. Routine preprocedure lab
tests include CBC, coagulation tests, and renal func-
tion tests. Patients may have impaired renal func-
tion due to previous nephrectomy for RCC. These
patients need to be sufficiently hyd rated before the
embolization procedure. The amount of contrast
media given during the procedure should also be
limited if possible. For patients who have significant
coagulopathy, correction is necessary with Vitamin
K or transfusion of fresh frozen plasma or platelets.
Placinga Foley catheter may be helpful, as the embo-
lization procedure can be lengthy if multiple tumor
feeders need to be embolized, and since the patient
may have a pathological fracture, ambulation could
be difficult. Furthermore, for patients with a pend-
ing pathological fracture, early ambulation postem-
bolization mav complicate The pathological fracture
[19]. A review of available imaging studies is impera-
tive for choosing a treatment plan. Consents for the
procedure and conscious sedation are obtained rou-
tinely. Whether or not one should give prophylactic
antibiotics routinely before the procedure is contro-
versial. Most authors do not prescribe antibiotics for
the purpose of prophylaxis [18-20].
15.3.3
Angiographic Technique
Most preoperative embolizations can be performed
under intravenous conscious sedation via a trans-
femoral approach. Lesions in the proximal femur are
treated from the contralateral approach. Lesions in
the distal femur may be accessed in an ipsilateral
antegrade fashion to facilitate catheter manipula-
tion [19]. For lesions located in the pelvis and upper
extremities, a right femoral approach is routinely
used. A5-F sheath is used for most procedures. A 5-F
Davis catheter, JB-1 or Cobra visceral catheter is com-
monly used for selective catheterization. Microcath-
eters such as the 2.9-F Renegate Super-flow (Boston
Scientific) through a coaxial system are used for
superselective catheterization that allows a safe and
effective embolization of the tumor feeders.
The pre-embolization arteriogram should be
started at the main territory artery in order to cover
the entire area and identify all tumor feeders. For
example, a distal abdominal aortogram or common
iliac arteriogram should be performed when a
tumor is located in the proximal femur, because
the tumor may derive blood from superior/inferior
gluteal arteries, medial/lateral circumflex femoral
arteries, and descending muscular branches from
the profunda femoris artery. In rare situations, the
obturator and internal pudendal arteries from the
anterior group of the internal iliac artery may also
provide blood supply to the tumor. The postem-
bolization arteriogram should include all possible
collateral pathways, because untreated collater-
als may become more prominent after occlusion
of other feeders (Fig. 15.1a-c). The amount of con-
trast medium given during an arteriogram must be
sufficient to make all possible tumor feeders well-
opacified. Therefore, in addition to an appropriate
injection rate, the period of injection should also be
long enough (lasting more than 3 sec). The acqui-
sition should be long enough to cover all phases
of the arteriogram (arterial, capillary, and venous
phase) to document tumor vascularity and arterial
to venous shunting. Frequently, multiple selective
arteriograms in different projections maybe neces-
sary in order to show the origin of a tumor feeder
in profile and facilitate superselective catheteriza-
tion. The fluoro-fade, or road mapping, technique is
available for use with most modern digital arterio-
graphic equipment. This is very helpful for superse-
lective catheterization, especially when a tumor is
located in the extremities (reduced artifacts caused
by movements of breathing and bowel peristalses).
15.3.4
Embolization Technique
Thus far, there has been no single embolic ager
that is ideal for preoperative embolization of bon
. Collateral supply of rumor vessels, a Pre-embohzation arte-
riogram. Tumor supply from Li ranches of :be i i t: [it Literal femoral circum-
flex [tinge arrow), profunda isin-.iii iin-n ui, .ind the superior gluteal (<UTpir
/i['i7i/t) arteries, b Supei se.e.tjve catheterization of the lateral femoral cir-
cumflex artery. Note th lU the desceuc.ing branches do not supply the tumor
■).c Arteriogram after em bo. izat ion of the tumor with PVA.Note sub-
traction artifact from coil [i-.n^c mi ■■.<«) thai was p.accfr into the descending
branch of lateral femoral cncumf.ex artery before l-'VA embolization. Also
note that gluteal s.ipp.y is more obvious after embolization of the main
feeders ismall at
metastases from RCC. An ideal embolic agent should
be easily delivered through a microcatheter, should
reach and permanently occlude small blood ves-
sels deep within the tumor, and should be nontoxic
and easy to prepare and control during delivery.
Different embolic agents have been used for pre-
operative embolization of bone metastases from
RCC, including absolute alcohol, tissue adhesives,
coils, gelatin sponge, Embospheres, and polyvinyl
alcohol particles (PVA) [11-20, 24-31]. The use of
liquid embolic agents (e.g., ethanol, tissue adhesive)
was not advocated for preoperative embolization of
bone metastasis since they may be associated with
a high rate of complications (even in experienced
hands) such as tissue ischemia, skin necrosis, and
neurologic impairment when used for spinal metas-
tasis [13]. Coils are a permanent embolic agent, but
they induce relatively proximal occlusion of target
vessels, and thus are less effective for decreasing
estimated blood loss (EBL), because bone metastasis
from RCC shows angiomatous vascularization that
may reconstitute collaterals within hours. Practi-
cally, it is not uncommon to find new tumor feeders
that were not evident on thepreembolization angio-
gram, immediately after the major feeders were
occluded. Coil embolization made no significant
difference in EBL compared with a control group
in hypervascular spinal lesions [13, 19]. The same
studies also suggested that the additional use of coils
after PVA particles provides no further benefit.
Gel loa in particles have been used in the early stage
of preoperative embolization of bone metastasis. Due
to the fact that it is biologically de tradable and not
definite in size, Gelfoam pledge only creates proxi-
mal and temporary occlusion of target vessels. Early
re canalization and revascularization of embolized
vessels have been observed, which resulted inunfavor-
able outcomes regarding EBL. Therefore, compared
.e Metastasis from Renal Cell Car
'.: Preoperative Embolization
with PVA particles, Gelfoam pledge is less reliable in
controlling intraoperative bleeding [10, 13, 19], and
it should be avoided in preoperative embolization for
bone metastasis from KCC, espet in II;' when surgery is
not to be performed within 48 h [19].
PVA particles are considered a permanent periph-
eral embolic agent, and have been used successfully
for the treatment of hemorrhage, vascular malforma-
tions, and tumors throughout the body [31, 32]. PVA
particles in sizes between 250 and 1,000 u.m were
used for preoperative embolization in the major-
ity of published series [14, 19-21, 32]. The technical
requirements are more demanding for PVA than for
larger embolization materials that can be deployed
more proximally, e.g. coils or Gelfoam pledges. Selec-
tive and superselective catheterization can provide
a safer environment for deploying PVA and reduce
the possibility of errant embolization, but caution
must be taken. Large anastomoses, such as those
between the inferior gluteal or the obturator arteries
and the femoral artery, may provide an escape route
for particles into nontarget territories [33]. The size
of the embolic material needs to be adjusted to the
size of these potential collateral vessels and the size
of existing A-V shunts, which are often present in
hypervascular metastases (Fig. 15.2a-g).
However, smaller particles (-200 fim in size)
should be used when a catheter or microcatheter can
be superselectively positioned in a small, peripheral
feeder that supplies the tumor only. Smaller PVA
particles can also be used when branches from a
tumor feeder that supply surrounding normal tissue
are protectively embolized with coils (Fig. 15.1a,c).
Occasionally, a main tumor feeder gives many
branches that supply most of the tumor, but bifur-
cates from a major branch supplying normal tissue.
In order to make the embolization safer, superselec-
tive embolization of each of tumor feeders will be
required, but is very time-consuming. Under such
a situation, coil embolization of the major normal
branch will make the procedure much easier and
safer. Embolization with smaller PVA particles by
means of a coaxial microcatheter system is more
effective, and complete obliteration of all tumor
blushes can be expected [13, 19]. This is partially
due to the fact that smaller particles make imme-
diate revascularization from vessels distal to the
embolized pedicles through existing collaterals less
likely. Immediate revascularization is frequently
seen when larger particles or proximal emboliza-
tion was conducted, which may give one the impres-
sion that complete obliteration of the tumor blush
can never be achieved. It is also frustrating for the
operator because the new tumor feeders are usually
too small to be catheterized, not to mention the time
one has to spend.
Nonetheless, when embolizing an artery that
may supply important structures with a smaller size
of PVA, great care must be taken to avoid nontar-
get embolization. For example, internal iliac artery
branches (mostly inferior and superior gluteal
artery) and deep femoral artery branches may supply
the sciatic nerve, buttock, and leg muscles. Emboli-
zation of these arteries may result in an inadvertent
event [33]. The embolization should begin with the
major pedicles and then proceed to the accessory
ones to avoid embolization through backflowof any
neighboring area. It is not uncommon to see that
the accessory feeders have already partially or com-
pletely occluded through the communication with
the major feeder when the major feeder has been
embolized (Fig. 15.3a-e). PVA is mixed with con-
trast medium for better fluoroscopic delectability
and more controlled PVA particle delivery. To keep
the PVA particles in suspension during the delivery,
many methods have been used. The most commonly
used technique is to perform, as frequently as possi-
ble, mechanical exchanges of the solution containing
PVA particles between two syringes on a three-way
stopcock. Ex vivo experiments showed that the best
PVA particle suspension could be achieved when the
ratio of contrast medium and normal saline was 6:4,
i.e., 60% contrast and 40% saline [28] . For better flu-
oroscopic visualization during the particles' deliv-
ery, full-strength contrast was also used with the
delivery syringe held upwards to keep the particles
floating on the top of the syringe [19]. The mixture
of PVA is manually delivered under fluoroscopic
observation. When the flow slows down or stagna-
tion is observed, the delivery is halted and residual
PVA is slowly flushed forward with normal saline.
Saline clearly defines the contrast material interface
and emptying of the catheter from particles [19].
15.4
Results
15.4.1
Obliteration of Tumor Blush /Estimated Blood
Loss
Intra- operative blood loss is the major criterion in
evaluating the el flaw vol preoperative embolization.
Significant intra-operative blood loss was defined as
Fig 15r>a-g. Fifty- iiine-ve.M-0:d female with RC'Z metastasis of left proxi-
mal hunter lis ana i:r.pe:'.dHig fracf.ue. i-'VA i.i?i)-L;ni i enfnolizatic-n with
obliteration of t timer stain by more than l ">0 c 'v ai'.d intra-opeiative blood
loss of 350 ml. li Arteriogram showed hypervascul.M- uimor in the left
proximal humerus supplied oy lateral circumflex aj terv. b Venous phase
showec s i gniric, i m iLimcr ~= Ili z=Jj .mi," A-V shuntii'.g : : r f " .■ L "■■ s). c PosteMbQ-
l:7,i : ion arleric-gi urn with catheter tip at the major feeder shows complete
occlusion of the feede: with no tumor oltish seen : :;ii::n).d Arteriogram
with catheter pulling b-aciv shows ■,-, minor tumor feeder supplying part of
lite tumor (anoirsi. e $uhselective pc-steinbohzation arte! iogfjm shows
tout! occlusion of the minor feeder fan-on.'), f Arteriogram after repo-
sitioned catheter to the r.istal subclavian artery shows iMiollte: minor
feeder with tumor h-iush, winch was less evident before the other two
tumor feerlers were embolized i^ncuij. g Late-phase arteriogram .Lite;
the thud feeder embolized will! citlieter positioned at proximal subcla-
vian artery shows complete occlusion of all tumor feeders
.e Metastases from Renal Cell Carcinoma: Pre
Fig 15.3a-c. Left glenoid solitary RCC metastasis, s/p pre-operation
embolization with PVA (350-500 |im), estimated blond loss of 75-
100m!. a P re-em bolization arteriogram showed the communication
oetween I wo- mm or feedeis iiirw.: sj. b 5,'p embolization of the maior
feeder, selective ane::og:am shows pa ;' : i a I ly C'Ccmded miner feeder
wiih shiag.sh flow liiiioir;. c Comaleie.v embol.zed feeders with no
".iimor stain identified
a loss of more than 600 ml of blood from a lesion
of extremities or 1,200 ml from a pelvic lesion [10].
The amount of blood loss has been positively cor-
related with the percentage of obliteration of tumor
blush I OTB) piisiemholizalion. The more tumor
feeders embolized, the better EBL results that could
be achieved. Different categories for rating OTB that
resulted in a significant difference in EBL have been
used [13, 15, 19, 20]. Achieving greater than 70% or
75% of OTB was recommended in order to effec-
tively reduce intra- operative blood loss [15, 19]. For
peripheral lesions, patients with OTB >70% had an
average of 550 ml EBL, which was significantly less
thanpatients with OTB of <70% [15, 19]. With proper
embolization technique, sufficient OTB could be
obtained in more than 75% of patients who under-
went preoperative ejnboliz.it ion [19]. Some authors
used the criterion of complete/incomplete OTB to
indicate the success of the procedure [13, 20]. An
average of 535 ml EBL (ranging from 200-1600 ml)
was observed in patients who had complete OTB.
However, complete OTB could be obtained only in
36% of all patients [20]. EBL did not significantly
correlate with tumor size or vascularity prior to
embolization [19]. The effect of embolotherapy on
OTB was based on a planimetric comparison of pre-
and fostemloolizahoii arteriograms [19], ("mises [in-
patients with <70% of OTB were multifold: (1) severe
tortuosity and irregularity of vessels secondary to
remarkable atherosclerotic disease precluded super-
selective catheterization; (2) tumor feeding vessels
that arose directly from a limb- supplying artery
were so small that a microcatheter could not be
seated well enough for embolization without risk of
nontarget ischemia (Fig. 15.4a,b); and (3) proximal
embolization with coils or Gelfoam pledge [19].
It is generally recommended that surgery be per-
formed within 24 h after embolization, since flow
re constitution through collaterals increases with
time [14]. For patients who were embolized with
coils only and who were operated more than 48 h
after embolization, significant intraoperative blood
loss was encountered during the surgery. This high
blood loss was observed although more than 70%
obliteration of tumor blush had been achieved in
some patients [19]. The small number of patients
makes it difficult to assess whether this result is
related to the type of embolization material or the
timing of surgery. In patients who were embolized
with smaller-sized PVA, the timing of surgery may
not be critical; there was no significant difference
in EBL between the patients who were operated on
g 15.4a,b. Obliteration of ;nmor si.- in oy 00%, 700 ml of estimated blood loss. survival j months, a Pre -embolization arte-
riogram showing a hype: vascular lesion in the rig lit r.islal ft in ur. The branches supplied a tumor arising directly from the
poolitea! a:\ery; many of ihem vvere too small for s.ile embolization Mi tousi. b f'os'.emb' 'kzation ,11 lei :■ 'gum vci;h residua!
within 24 h and those who had surgery 36 to 120 h
after embolization. Use ot'PVA in cases of an antici-
pated delay in surgery is therefore recommended
[19].
15.4.2
Osseous Healing and Survival
Bone healing can be affected adversely by many
variables, such as presence of tumor cells, poor
local blood supply, systemic disease, malnutrition,
corticosteroid therapy, and iatrogenic inference [34,
35]. Preoperative embolization has the potential to
induce ischemic changes in the tissues adjacent
to the tumor and may theoretically interfere with
osseous union. However, there has been no evi-
dence of delayed postoperative healing or nonheal-
ing reported in the literature [10, 19, 34, 35]. In all
reported patients, bone healing ensued as evidenced
by radiography, progressive callus formed at 3 and
6 months, and hardware was in place without com-
plication (Fig. 15.5a-e). When bone healing was evi-
dent, functional recovery largely depended on the
type of surgery the patients received.
The oncological objective of excising metastatic
RCC of bone is the achievement of local tumor con-
trol. Patient survival is determined by metastatic
disease at other sites, inherent biological behavior
of the tumor, and tumor response to adjuvant treat-
ment modalities. Therefore, the rate of local recur-
rence is the most appropriate criterion by which
to evaluate the oncological adequacy of resection
margin [10].
The appropriate goal of pre -operative emboliza-
tion is to decrease intra-operative blood loss, fol-
lowed by reduction of the amount of blood transfu-
sion and surgical morbidity/mortality. As a result,
shortened duration of surgery and hospital stay can
be expected [10, 19, 25]. A median hospital stay of
8 days was reported with minimal surgical compli-
cations in a relative large surgical series [10]. Res-
toration of musculoskeletal function and release of
pain therefore are paramount for the quality of life
of these patients [19].
15.4.3
Complications
Postembolization syndrome (PES) it
occurrence after pre-operative embolization of bone
metastases. It was reported that PES is not neces-
sarily regarded as a complication [36]. Marked PES
may indicate a successful embolization and has been
associated with a good clinical response to the embo-
.e Metastases from Renal Cell Car
'.: Preoperative Embolization
Fig k"."a--d. Obi iter.; I ion o:' iumor stain by mo:e tha:'. t !?'o. Iniracpei alive bloo; loss of 100 mi. survival 0-1/2 yvars wi:h norma!
healing jn; ljmiup.ared function of her left uppe: extremr.y. a,b Pre-^nbolizaiion; c,d poslenfLicazalion. a Plain ladiograofi
vmh la:ge ■. -^:e- 'lv:io .esi..:: of ih e let": humerus aiv.i paihol igie iraouire : -.a ■ ei:>:. b E.irly a: :ei iai oaase showing hvpervasoulai
c Arteriogram ,i:'ter "■■.aerse;eo:iv- embolization o) the let": ."ire 1 .: mil ex humeral ai;e:ies with 500-|.im PVA particles
i'j). d Radiograph -■:■ months after ein notation and surgioal repair shows [lorm.ii ocne heaang w-i:h hardware in place
{"'
")
lization [36]. Common symptoms are fever (usually
below 38°C), malaise, and pain. PES usually subsides
within 3-5 days without treatment. However, severe
PES niav deter ri surgeon from im mediate interven-
tion. When PVA particle is used, such a delay should
not have adverse effects on intraoperative blood loss.
Reported complications include non target emboli-
zation, skin necrosis, and ischemic ulcer [36]. One
spontaneous pathologic fracture was reported 12 h
after the embolization with PVA and additional
coils. More than 95% of obliteration of tumor blush
had been achieved by superselective embolization in
this patient (Fig. 15.6a-e). The patient reported no
apparent external forces on his leg after the emboli-
zation. It is conceivable that acute ischemic changes
following embolization in a hypervascular tumor
may cause volume changes eliciting a spontaneous
cortical collapse. Although patients with pending
fractures are already handled carefully, extra cau-
tion during patient transport and immobilization of
Fig 15.6a-e. Patient complicated
with pathologic fracture 12 h after
the embolization, a Plain radiograph
shows a large osteolytic lesion in the
proximal one-third of right femur
with impending pathologic fracture
(arrows), b A hypervascular lesion
supplied by branches of the
femoris artery (am; its), c Complete
embolization of tumor feeders. d,e
Plain radiographs show pathologic
fracture and surgical internal fixation
the affected extremity is recommended after embo-
lization [19].
While complications can be reduced through
abiding by proper technique, risks are higher in cer-
tain anatomic locations. During pelvic emboliza-
tion, occlusion of blood vessels supplying the sciatic 15.5
nerve may cause ischemic neuropathy, which can be Conclusion
avoided by sparing the inferior gluteal artery during
embolization. Also, muscle branches of the supe-
rior gluteal artery or deep femoral artery shi
be spared to prevent
emholixationshould 1
of tumor feeders with si
vertent embolization.
irticles to avoid
Retrospective studies are of limited value :
mining the exact effect of a certain form
Coil ment. Intra- operative blood loss depends
formed before emboliza- on the type of surgery, but the individual
skills of
.e Metastases from Renal Cell Car
'.: Preoperative fimholiza
surgeon as well. Theoretically, a prospective and
randomized study would be desirable for precisely
evaluating the effects of pre-operative emboliza-
tion. However, according to the nature of clinical
studies, the necessity and possibility of conducting
such a study are in question. Practically, pre-opera-
tive embolization ol hypervnsailar bone metastases
from renal cell carcinoma is a safe and minimally
invasive procedure in experienced hands. Best
results can be achieved with the use of PVA particles
and when >70% of tumor blush is obliterated. This
has become a standard pre-operative procedure for
patients with hypervascular metastatic disease of
bone from RCC.
Parker SL, Tong T, Bolden S and Wingo PA [1005) Cancer
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King GJ, Kostuik JP, McBroom RJ, Richardson W (1991)
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spine. Spine 16:265-271
Kessler O, Mukamel E, Hadar H et al (1994) Effect of
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Bowers TA, Murray ]A, Charnssngayej C, Soo CS, Chuang
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Manke C, Bretschneider T, Lenhart M et al. (2001 ) Spinal
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Carrasco CH (1991 ) Embolotherapy of bone and soft-tissue
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Gellad FE, Sadato N, Numaguchi Y, Levine AM (1990] Vas-
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s.Keller FS, Roach I, Bird CB (1983) Percutaneous emboliza-
iion or bony pelvic neoplasms with tissue adhesive. Radiol-
ogy 147^1-27
S.Rowe DM, Becker GJ, Rabe FE et al. (1984] Osseous metas-
tases from rena, cell carcinoma: embolization anc. surgery
for restoration of function. Radiology 150:673-676
7. Barton PP, Waneck RE, Karnel FJ et al. (1996) Embolization
of bone metastases. J Vase Interv Radiol 7:81 -88
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?. Chatziioannou AN, lohnson \!E, Pneitmaticos SG et al.
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Arthroplasty Arthrosc Surg 7:80-821 8
i. Rossi C, Ricci S, Boriani Set al (1990] Percutaneous trans-
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5. Olerud C, Johnson H Jr. Lofberg AM et al. (1993) Emboliza-
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16 Embolotherapy for Organ Ablation
David C. Ma
6.1 Eraboloiii e:\ipv m M judgement or Keiul
Tumors 201
6.1.1 Introduction 201
6 I .'. A 'xi: mil and Angiographic Consideralior
6 .1 I'.vl:*' .„■■.. Considerations 203
6.!.; Results 207
6.1 .4.'. Krabolottlerapy for Renal Cell Car
6.1 .4.2 Embolotherapy for Angiomyolipor
6.1.5 Future Directions 211
6.2 Embolotherapy in Management
of Hypersplenism 211
6.2.1 Introduction 211
6.2.2 Anatomic Considerations 2J2
6.2.3 Technical Considerations 212
6.2.4 Results 214
6.2.5 Future Development and Research
6.3 Conclusion 215
References 217
16.1
Embolotherapy in Management of Renal
Tumors
16.1.1
Introduction
Malignant tumors of the kidney and renal pelvis
accotint for -3% of all adult malignancies. There
were -31,200 new cases in 2000 contributing to
-11,900 deaths in the United States [1]. Renal cell
carcinoma is the most common primary malignant
tumor of the kidney and occurs in both sporadic and
hered itary forms [2]. Most cases are sporadic, but at
D. C. Madoff, MD; R. Verua, MD; K. Ahrar, MD
Section of Interventional kiidiology, Division of Diagnos-
tic Imaging, The "University of Texas, \'I> Anderson Cancer
Center, 1515 Holcombe Boulevard, Unit 325, Houston, TX
77030-4009, USA
least four forms of hereditary renal carcinoma have
been identified. The most studied form of heredi-
tary renal cancer is von Hippel-Lindau syndrome, in
which affected individuals have a predisposition to
develop tumors in various organs, including the kid-
neys. In the hereditary syndromes, kidney cancer
is often bilateral and tends to occur in younger
patients. Renal cell carcinoma may remain clinically
occult for most of its course; the classic presentation
of pain, hematuria, and palpable mass occurs in
only 9% of patients. Approximately 30% of patients
with renal cell carcinoma present with metastatic
disease, 25% with locally advanced tumor, and 45%
with localized disease. Widespread use of routine
abdominal imaging has led to increasing detection
of smaller lower stage renal tumors [3]. Therefore,
the natural history of renal cell carcinoma may be
changing [3]. Historically, radical nephrectomy was
considered the only effective treatment for patients
with renal cell carcinoma. More recently, nephron-
sparing surgery has been accepted as an alternative
for smaller tumors (less than 4 cm) localized to the
kidney [3]. Although promising for the management
of smaller tumors, energy ablat ive therapies, includ-
ing cryotherapy and radiofrequency ablation, are
investigational and are reserved for patients who
are not good surgical candidates, patients with only
one kidney, and those with multiple bilateral tumors
[4, 5]. Metastatic renal cell carcinoma is unrespon-
sive to conventional chemotherapy used to treat
other metastatic solid tumors, but treatment with
immunotherapy has resulted in durable responses
in selected patients [3]. Before the era of immuno-
therapy, the course of metastatic renal cancer was
not affected by debulking nephrectomy, and surgery
was reserved only for palliation ot svmptoms. Recent
trials of nephrectomy and immunotherapy versus
immunotherapy alone have demonstrated statisti-
cally significant improvement in overall survival in
patients with metastatic renal cell carcinoma [6]. In
light of these findings, nephrectomy has become
the initial component of multimodality therapy for
liietii.itatic renal cancer.
P. C. Madoffel
Surgical resection of larger i
is challenging because both the kidney and the
tumor are extremely vascular and dissection of
the tumor may lead to clinically significant blood
loss, necessitating replacement of a large volume
of blood. In addition, renal hilar lymph nodes may
interfere with visualization and access to the vas-
cular pedicle [7]. Early ligation ot T lie renal .me it
is necessary to avoid substantial bleeding, but the
renal vein lies anterior to the artery and may be
encountered before the renal artery. For these rea-
sons, starting in the 1970s, the technique of renal
artery embolization was popularized as an adjunct
to surgery. Since that time, embolization has been
used before resection of larger tumors and tumors
invading the renal vein or inferior vena cava [8,
9]. When used appropriately and in the right set-
ting, the technique purportedly decreases intra-
operative blood loss and creates a plane of edema
that facilitates the dissection of the tumor [8].
The same technique has been used for palliation
of patients who may not be surgical candidates.
Renal artery embolization has been used to allevi-
ate tumor-related symptoms like hematuria, flank
pain, paraneoplastic symptoms such as hypercal-
cemia or polycythemia, congestive heart failure,
and hypotension [10, 11]. Other potential, but as of
yet unproven, benefits of renal artery embolization
include inhibition of tumor growth and improved
rarvival [12].
Angiomyolipoma is generally a benign tumor
of the kidney, although a more aggressive sub-
type (epithelioid angiomvolipoma) has also been
described [13]. The tumor is composed of mature
fat cells, vascular tissue, and smooth muscle in
various proportions. Clinically, angiomy.'lipi:
eoft
Table 16.1. Clinical
contemporary surgical
> distinct settings. It may be
Tuberous Sporadic p-vatue
sclerosis- angiomyo- (chi-squar
associated lipoma test)
angiomyo-
Upon..
Mean age 30.3
Tumor diameter fern) 8.9
% Multiple tumors 97
% A- presentation:
- Symptomatic 64
- A.rute hemorrhage 44
l: Nelson and Sanda [13] -(printed with pi
associated with the tuberous sclerosis complex,
which is an autosomal dominant disease with
incomplete penetrance. The triad of seizures,
mental retardation, and adenoma sebaceum char-
acterizes tuberous sclerosis in its classic clinical
presentation. More commonly, angiomyolipoma is
encountered sporadically in individuals who oth-
erwise have no clinical features of tuberous sclero-
sis. Angiomyolipoma is also associated with pul-
monary lymphangioleiomyomatosis. The clinical
presentation of angiomyolipoma maybe similar to
that of renal cell carcinoma. Patients may present
with flank pain, a palpable tender mass, or gross
hematuria, and possibly nausea, fever, hyperten-
sion, or anemia. In patients with tuberous sclerosis
and multiple a ninomvohpomas, renal insult ideiR'v
or failure may be the initial sign of the tumor. The
most dramatic and life-threatening presentation of
angiomyolipoma is spontaneous retroperitoneal
hemorrhage. Angiomyolipomas associated with
the tuberous sclerosis complex are often multiple,
bilateral, and larger at presentation. These tumors
are more prone to spontaneous hemorrhage than
their sporadic counterparts (Table 16.1).
Before 1976, 93% of reported angiomyolipomas
not associated with tuberous sclerosis were treated
with total nephrectomy, whereas in 1984, only 50%
of all angiomyolipomas reported in the literature
were treated with total nephrectomy [14]. Because
of advances in embolization and partial nephrec-
tomy techniques, most angiomyolipomas are now
treated conservatively where the goal is control of
symptoms, prevention of life-threatening hemor-
rhage, and preservation of renal function. Other
than patients who present with spontaneous bleed-
ing and require urgent treatment, the timing of
intervention for ajigiomyollpoma remains a sub-
ject of debate. In one study, 90% of symptomatic
tumors were 4 cm or larger and 64% of asymptom-
atic tumors were smaller than 4 cm [14]. In another
study, small (less than 4 cm), medium (4-8 cm),
and large (greater than 8 cm) tumors were symp-
tomatic in 10%, 54%, and 100% of cases, respec-
tively [15]. Primary indications for intervention
include pain, retroperitoneal hemorrhage, and
hematuria regardless of tumor size, but prophy-
lactic intervention is reserved for larger tumors in
high-risk patients, in females of childbearing age,
and for those patients for whom follow-up or access
to emergency care may be inadequate. Regardless
of the indication, preserving renal tissue and func-
tion is a significant concern when treatment is con-
templated.
Embolotherapy for Organ Ablat
16.1.2
Anatomic and Angiographic Considerations
A thorough understanding of the renal vascular
anatomy is a prerequisite for successful emboliza-
tion of renal tumors and helps minimize inadvertent
nontarget embolization. Most commonly, a single
renal artery to each kidney arises from the abdomi-
nal aorta at the level of L1-L2 disc space. Multiple
renal arteries to one or both kidneys may be pres-
ent in 12%-32% of individuals [16]. The main renal
artery frequently divides into anterior and posterior
branches. Because of the location of the kidney in
the retroperitoneum, the ventral or anterior divi-
sion of the renal artery supplies the lateral border
of the kidney in an anteroposterior angiogram,
whereas the dorsal or posterior division provides
blood supply to the medial border of the kidney. Fur-
thermore, the anterior division appears as a direct
continuation of the main renal artery, whereas the
posterior division is smaller in caliber and appears
as a branch of the main renal artery [17]. Branching
of the renal arteries continues to form segmental,
lobar, interlobar, and arcuate arteries. The arcuate
arteries are end arteries and do not anastomose with
one another; instead, they subdivide into interlobu-
lar arteries, which in turn give rise to afferent glo-
merular arterioles [18].
Perforating arteries, an important collateral path-
way to the kidney, arise from the intrapareikhyma!
branches of the renal artery and exit from the kidney
to anastomose with various retroperitoneal arteries
[18]. In addition to the main renal artery and per-
forating arteries, the superior, middle, and inferior
capsular arteries should be considered as well. The
superior capsular artery may arise from the infe-
rior adrenal artery, main renal artery, or aorta. The
middle capsular artery, which may consist of one or
more branches, arises from the main renal artery.
The inferior capsular artery may originate from the
gonadal artery, an accessory or aberrant lower pole,
or even the main renal artery. These vessels form a
rich capsular network that anastomoses freely with
perforating arteries and other retroperitoneal (espe-
cially lumbar) arteries and also with internal iliac,
intercostal, and mesenteric arteries [18].
Angiography is no longer performed in the diag-
nostic workup of renal masses and is reserved for
therapeutic interventions only. The study should
start with an abdominal aortogram to determine the
number and location ot arteries supplying the kidney
and the tumor. Selective catheterization and angiog-
raphy of each feeding artery is performed to assess
the extent of neovascularity, degree of arteriovenous
shunting, and risk of nontarget embolization.
Most renal cell carcinomas appear hypervascular
on angiography (Fig. 16.1} and demonstrate tumor
vessels that are irregular, tortuous, randomly distrib-
uted, variable in size, and unpredictable in branching
[19]. Other findings may include pooling of contrast
in dilated vessels, arteriovenous shunting, staining of
the tumor during the capillary phase, mid renal vein
invasion or occlusion by the tumor.
The angiographic appearance ot a iii:i.i myoli-
poma is that of a hypervascular mass with a large
feeding artery [19]. The vascular components of the
tumor are thick-walled arteries characterized by
the absence of the internal elastic membrane and
a disordered adventitial cuff of smooth muscle,
which results in the numerous saccular aneurysms
frequently seen on arteriograms. Tortuous vessels
may be circumferential!;' arranged in the arterial
phase. Overall, a stinburst or whorled appearance
in the nephrography and venous phases is sugges-
tive of these tumors. Arteriovenous shunting is not
a prominent feature ot angiomyolipomas.
16.1.3
Technical Considerations
The size and extent of the tumor, the need to pre-
serve any of the renal parenchyma, and the overall
goal of embolization should be considered in plan-
ning embolotherapy of renal tumors. Historically,
the choice of embolic agents depended on the expe-
rience and preference of the operator. Although
more than twenty embolic agents have been used
(Table 16.2), it is most worthwhile to consider three
classes of embolic agents currently used for emboli-
zations of renal tumors: liquid agents (the prototype
of which is absolute ellianol), particulate materials
(the prototype of which is polyvinyl alcohol foam},
and metallic coils.
A recent review of the literature demonstrated a
trend toward the use of ethanol for embolization of
renal tumors [20]. Ethanol is a nonviscous liquid,
and after it is injected into the main renal artery, it
diffuses into the distal vascular bed of the tumor,
potentially causing tumor necrosis rather than
simple occlusion of the embolized artery [21]. Trans-
catheter administration of ethanol is technically
easy, and theoretically, reflux of a small amount of
ethanol may not be as toxic as other embolic agents
to other organs of the body because alcohol dilutes
rapidly in a large volume of blood [22]. In reality,
D. C. Madoff et al.
Fig.16.la-c. A 42 -year-old man with heirralaria was referred
for preoperative embolization o\ a large renal tumor. Axial
CT image of die abdomen ia; shows a large enhancing renal
with tumor thrombus extending lo the inferior vena
(IVC). Selective right :c:'.a! arteriogram (b) shows neo-
larity of the tumor. Arteriogram after embolization
lc) shows complete occlusion of renal artery branches and
complete devascikanzation of the tumor. At surgery, the
right l-.idniry, adrenal gland, and [VC tumor thrombus were
resected. Patient repaired trail -fa -ion of :wo units of packed
red blood cells
however, reflux of ethanol can lead to nontarget
embolization of the inferior mesenteric artery and
the lumbar arteries [11, 23-26].
Ellman et al. [21] first described ablation of renal
tumors with absolute ethanol. On the basis of their
experience with an animal model and six patients,
they recommended selective injection of ethanol at
s many tumor arteries as pos-
ted that injection of ethanol at
iults in tissue toxicity, thereby
the perivascular areas, '\ltuig-
l small arteries and glomeruli,
tall arteries; subsequently, the
ged and sloughs over several
hours, resulting in complete occlusion of damaged
vessels. Ellman et al. further elaborated that slow
injection of ethanol (0.1 ml/s) results in little direct
tissue toxicity and that instead, small clumps of
i rate of 2 ml/s i
sible. They hypothes
a rate of 1 to 5 ml/s n
leading to necrosis ir
ing" of erythrocytes
and spasm of these s
i-aclc'thelium is dam
damaged erythrocytes and denatured proteins lead
to proximal occlusion of the arteries. The desired
angiographic end points were described as occlu-
sion of all arteries smaller than major segmental
branches, stagnation of flow in patent major arteries,
and extravasation of contrast material into the
parenchyma. According to their report, injection ol
1 ml of ethanol per4 lb (1.8 kg) of body weight results
in a systemic blood ethanol level of about 50 mg/dl,
which is half the intoxicating level of 100 mg/dl and
far below the toxic level of 500 mg/dl.
In a modification of the technique of Ellman
et al., Rabe et al. [22] used an occlusion balloon
catheter in eight patients. In this technique, the
occlusion balloon is inflated in the main renal
artery (Fig. 16.2), and ethanol is injected at a rate
of 1 to 5 ml/s. The balloon is kept inflated for 10 s to
2 min, and after 10 min, the catheter is aspirated to
!-_ it.iL>-- "■ I. Mil e:.ipv :'.:■[■ Organ Ablation
Table 16 J. Agents li-ed for diempeulic embolization of renal
n alphabetic. I order
:e ethanol
Autologous muscle particles
Avitene (microfibrillar collagen hemostat)
Coils (nretaU steel / mini / Gianturco / GAW)
Collagen
Detachable balloons
Dura particles
Ethibloc (oily contrast- labeled amino acid)
Fibro spurn
■ 7- e ' M : i j j foam / . 7- ■=■ L lo ;i j j i
Gelatin sponge / GeLtspon
Gelfoam prepared with BCG
Histoacryl
Ivalon (polyvinyl alcohol]
I C RA ( isobu ty 1- 2 - cy a no a cry late ]
Lyodura
MMC (microencaps'jlated or nonencapsdjied mitomycin C)
P.i.iiCi"':. i m ethyl n; ethacrylate)
Sp on go st an
Tachotyp flocculi
Thrombin
Vilan
From: Kal.man and Y'akenhorst [10] (primed with permis-
e residual alcohol from it. After the catheter
is flushed, a test injection is performed with con-
trast material. This sequence is repeated until total
occlusion of the main renal artery is achieved. The
advantages of using an occlusion balloon catheter
are several: the balloon interrupts renal blood flow,
markedly prolonging the contact time of ethanol
with the endothelium and thereby reducing the
volume of ethanol needed for complete ablation of
the target tissue; the balloon inhibits reflux into
the aorta; and with the use of a balloon catheter, the
main renal artery can be injected with ethanol and
selective catheterization of segmental branches is
not necessary. Rare et al. also suggested that injec-
tion of ethanol in the main renal artery without an
occlusion balloon is ineffective because ethanol
dilutes rapidly in a large volume of blood. Instead,
they endorsed the technique of Eliman et al. with
selective catheterization and embolization of seg-
mental arteries when a balloon occlusion catheter
could not be used.
Bakal et al. [7] described a variation of the bal-
loon occlusion technique. They performed all renal
embolizations during selective placement of an
occlusion balloon catheter in the distal main renal
artery. Estimates of ethanol volume needed for
embolization were made by test injecting contrast
material during balloon occlusion. After infusion of
the ethanol, the balloon was left inflated for 5 min.
As the balloon was deflating, gentle suction through
the distal endhole of the catheter prevented reflux of
residual ethanol or thrombus into the aorta. Unlike
the study by Rare et al., no attempts were made
to selectively catheterize or embolize other tumor
vessels; embolization of the kidney rather than the
tumor was the intended effect. The retrospective
analysis of Bakal et al. demonstrated that complete
ablation of large, hypervascular tumors was asso-
ciated with a significantly reduced blood transfu-
sion requirement at nephrectomy, whereas tumors
that were partially ablated (accessory renal arteries,
polar branches, or lumbar arteries were not embo-
lized) required larger amount of blood transfusion
than the control group did.
Absolute ethanol is readily available, inexpensive,
and easy to handle, but its major drawback is that
it is not radiopaque. Early experiments in mixing
ethanol with radiographic contrast resulted in pre-
cipitation of the mixture [22]. However, ethanol may
be mixed with iodized oil (Lipiodol or Ethiodol) in
a 1:3 mixture for successful embolization of angio-
myolipomas [27]. Konya et al. [28] suggested that a
1:1 mixture of ethanol and iodized oil followed by
absolute ethanol may be an effective embolic agent
for ablation of renal tissue.
Particulate materials, such as absorbable gela-
tin sponge (Gelfoam) and polyvinyl alcohol foam
(Ivalon), have been used alone and with metallic
coils [29]. Newer embolic agents such asEmboGold
Microspheres (BioSphere Medical, Rockland, MA)
and Contour SE (Boston Scientific; Natick, MA)
are also used for embolization of renal masses,
but no reports of their effectiveness or lack thereof
are available in the literature; theoretically, these
newer agents should not be any less effective than
Gelfoam or Ivalon. There is no scientific evidence
pointing to a particular particle size for emboliza-
tion of renal masses. Despite the lack of informa-
tion, some recommendations can be made here.
In general, distal embolization of the tumor bed
rather than proximal occlusion is desirable; there-
fore, embolization should start with particles small
enough to avoid proximal occlusion. Hyper
lar renal tumors may have considerable a
nous shunting, and nontarget embolization of the
pulmonary bed is a concern. In tumors with rapid
arteriovenous shunting, the use of a sclerosing
agent such as ethanol or larger particles may be
prudent. The use of coils for palliation of tumors
is discouraged because renal tumors in advanced
stages often have an extensive collateral blood
supply, rendering proximal occlusion of the feed-
ing arteries ineffective. Furthermore, many tumors
require additional interventions, so arterial access
D. C. Madoff et aL
.a and right flank pain was referred for pallia-
tive embolization. Selective digital s.c. refaction angiogram of the right main renal artery ;aj shows early [".furcation of the
renal aneiv, n.eovascularily. tumor soain, jno scosiamial aneriovenoi.s shinning. The mferio: vsi^a cava is opacified in the
background. After place men I cc" .in occlusion balloon catheter il>), ti'.e anterior branch -:A the renal arterv was embolized wiih
I ml of dehydrated alcohol ! absolute ei ha noli. Selective angiogram of Ir.e posteiior branch ot" the righ: renal arterv ;c; snows
blooo supply to ihe reminder of the tumor. Embolization, of mis branch was completed using EmboGo.d Microspheres. Selec-
live angiogram o: ti'.e main rena. artery id! shows complete occlusion of bolh anterior and posterior branches. The tumor is
completely devascularized
to the neoplasm must remain intact [30]. If coils are
used for preoperative embolization, they should be
sized and placed appropriately to minimize the
risk of dislodgment at the time of surgery and to
avoid difficulties with renal artery clamping or
ligation [29].
Although firm scientific evidence is lacking,
complete embolization of the renal tumors may be
a desirable end point both for preoperative and pal-
liative purposes [7, 11, 27, 31]. Because most renal
cell carcinomas are hypervascular and often recruit
collateral blood supply from other sources as well,
many operators use a combination of techniques
and embolic agents to achieve complete emboliza-
tion (Fig. 16.2). Therefore, it seems appropriate for
the operator to be familiar with various techniques
and have access to a full complement of different
embolic agents.
iimbo I. vrli e:.ipv :or Orpin Ablution
16.1.4
Results
16.1.4.1
Embolotherapyfor Renal Cell Carcinoma
Renal artery embolization was popularized by Alm-
gard in the early 1970s. Over the next two decades,
investigators debated the usefulness of embolother-
apy in the management ol renal cell carcinoma, but
the decreasing number of reports in the literature
since then indicates a loss of interest in this tech-
nique over time, particularly in the last decade. Most
of the published reports are now over 20 years old.
Angiography, catheterization, and embolization
techniques have evolved over the last three decades.
A review of this older literature, which may not be
reflective of the current practice of embolotherapy,
is nevertheless warranted to elucidate the evolution
of the technique, point out some of the shortcom-
ings of previous studies, and highlight questions
that remain to be answered.
In 1999, Kalman and Varenhorst [20] pub-
lished a survey of the pertinent literature which
appeared during 1973-1997 on renal artery embo-
lization for management of renal cell carcinoma
(Table 16.3). Each one of the selected articles pre-
sented a minimum of 20 embolization cases, and
each study aimed to investigate the clinical effect of
embolization. All reports were scrutinized for study
Table 16.3. Case sei
:e^ : ■.'. biis:: ed in i:ie - :■«.!■■:: .ke:,i:iu e. i
n order of year c
fpublicatior
■., agents used for the
pen tic embolizatio
n, number of
patients, and indication for embolization
First Author
Year of
Method
Number of
Pre-
Palliative Not
publication
L\iiie:iis
oper.iiive
specific
AlmgArd [45]
1977
Muscle particles
38
29
9
Fhasson [49]
1978
Gelfojim
35
10
ScBttLMAN [141]
1980
Coils
Geltornu
Gelfoam + coils
ICBA
3
10
9
26
2
Frasson [50]
1981
Coils
Gelfoam
Gelfoam + coils
ICBA
Muscle particles
3
2
241
-
Gnn.iANAl53]
1981
Coils
1
Gehl.n fo;ini
40
ICBA
25
Kato [142]
1981
Encaps MMC + gel
Sponge
33
23
10
Mobilio 148]
1981
Geif '.iir.
ICBA
f
1
Wallace 129]
1981
Gelfoam + coils
100
26
Le Glillol- [143]
1982
No: specified
247
203
44
Teasdale [144]
1982
Coils
3
Gelfoam
22
26
2
Gelfoam + coils
3
Bono [39]
1983
Avitene
47
47
Geltoum
48
48
ICBA
4
Nakano [36]
1983
Gelatin sponge
ICBA
21
12
9
Ekelund [40]
1984
Et!:.inol
20
Kafsary [35]
1984
Coils
Gelatin sponge
55
49
Thrombin
C omnium ions of the ,ibo
KUHTH [32]
1984
Coils
Etlianol
Gel to;; in
25
25
ICBA
Table 16.3. Continued
First Author
Year of
Mel::od
Number of Pre-
pilNkMi-.
p :-.i. . e i u s
opera ti
Mcivor [33]
1984
Coils
Dura particles
29
29
Geli"' ;;i:"r.
Thrombin
Mebust [52]
1984
Coils + gelatin sponge
Elhanol
5
4D
Christens en [42]
1985
Coils
36
36
GOTTESMAN [41]
1985
Coil + Gelfoam
30
30
Klimbehg [8]
1985
Elhanol
25
21
Lavimer [24]
1985
E-.h,ni::i|
7
85
81
[v.: Ion
25
Leinonen [38]
1985
Edionol
12
10
Wejgel [34]
1985
H:hoi]:nl
22
22
Chudacek [145]
1986
r:.hil- ,:-:
Vilan
30
Karwowski [146]
1987
Gelfoam
81
Palliative Not
[•AT- [40]
UwnUH [4:
Bakal [7]
E7I1..1110I
ICBA
Ethanol
Ethanol + coils
Gelfoam
Gelfoam + coils
ICBA
ICBA + coils
ICBA + coils + Gelfoam
Detachable balloons
Hi' : k'.K:y.
Ivalon
Coils
i .jclj"i;;"i:r.
Ivalon
Gelfoam + BCG
Encaps MMC
K j l ^ Li y-^ MY.'Z - Gclto.im
Elhanol
Ethanol
Ethanol + coils
Ethanol + Gelfoam
Ethanol
1st [20]-( with modification,]
design, control-comparison group, recruitment,
patient selection, tumor stage, method of emboli-
zation, delay between embolization and operation,
measurement of intended outcome, adverse out-
come of treatment, and assessment of the extent to had historical control
which therapeutic embolization provided a solution spective randi
to the clinical problem.
Of the 51 publications, only 7 were prospective
studies [8, 32-37]. The remainder were retrospec-
tive studies, or the study design was not specified.
Most studies were from observation, and only four
i. As of 2004, no pro-
trial of renal artery
embolization has been reported. The methodologic
!-_ it.iL>-- "■ I. Mil e:.ipv :'.:■[■ Orenn Ab hit ion
weaknesses of the published studies make it diffi-
cult to compare the reports and draw firm conclu-
sions; therefore, evidence regarding renal artery
embolization in the literature is weak and must be
interpreted with caution.
Recruitment of patients to the studies on preop-
erative embolization varied widely. Some investiga-
tors included patients with "large primary tumors",
and others recruited patients with tumors larger
than a specified diameter [34, 38, 39]; one study did
not consider tumor size as a selection criterion [24].
Eligibility criteria for palliative embolization were
more commonly reported lis palliation ot pain, hema-
turia, or life-threatening endocrine tumor activity
[11, 24, 37, 38, 40, 41]. In one study, palliation was
not defined with respect to any symptoms but as an
alternative therapy for patients with advanced dis-
ease who were not surgical candidates [24]. Several
of the 51 papers reported on patients who underwent
either preoperative or palliative embolization. Over-
all, the studies varied greatly in their patient selec-
tion criteria, and details regard iiij; patient condition
and tumor stage were often lacking.
Over the span of three decades, more than 20
embolic agents have been used. Few authors used
one agent only for embolization in their study [8,40,
42-45]; most introduced combinations of agents or
used different agents for embolization in their trials.
Earlier studies used absorbable gelatin sponge and
coils, which are still used in preoperative devascu-
larization of renal tumors. For palliation, more per-
manent agents such as Ivalon and ethanol are pre-
ferred. More recently, absolute alcohol has become
the recommended agent for embolization of renal
tumors for all indications [7,43,44].
The time between embolization and nephrectomy
was reported in 34 of the 45 studies on preopera-
tive embolization. This interval varied trom 8 hours
[8] to 183 days [46]. In one study, a planned delayed
nephrectomy was thought to result in development of
edema and facilitate dissection [9], whereas another
study reported a more difficult dissection 3 days or
longer after embolization because of increasing col-
lateral circulation [47]. On the basis of the results of
the reviewed articles, Kalm an and Varenhorst [20]
concluded that the optimal delay between emboliza-
tion and operation was less than 48 hours.
Several variables have been considered in mea-
surement of the intended outcome, including intra-
operative blood loss. Twelve studies evaluated intra-
operative blood loss after renal artery embolization.
In three studies, blood loss was based on subjec-
tive estimation only [48-50]. One study compared
blood loss after embolization using ethanol and
Gelfoamand found no significant difference [38]. In
three studies, the difference in the amount of blood
loss in embolized and nonembolized patients was
not statistically significant [42, 43, 51]. One study
reported greater blood loss for embolized patients
compared with historical data, but an appropriately
matched control group was not selected [52]. Bakal
et al. [7] demonstrated that estimated blood loss is
an unreliable measurement and used instead the
transfused volume as a measure of successful pre-
operative embolization. They demonstrated that the
transfusion volume was statistically significantly
lower after embolization for patients with large,
hypervascular renal cell carcinoma (volume greater
than 250 ml, diameter larger than 7.8 cm) than for
smaller or hypovascular tumors. Another group
recorded a statistically significantly lower volume
of blood transfused in T3 and T4 tumors than in a
historical control group [53]. Some groups believe
that resection of renal cell carcinoma is facilitated
by preoperative embolization [8, 47]. Reportedly, a
plane of edema develops after embolization, making
dissection of the tumor easier. In tumors with exten-
sion into inferior vena cava, embolization causes the
tumor to shrink and facilitates its resection from the
vena cava [9]. In addition, in larger tumors extend-
ing to the renal hilum and perihilar lymph nodes,
preoperative embolization allows for ligation of the
renal vein before the renal artery, alleviating some
of the technical difficulties with resection of these
bulky tumors [8].
Only four studies reported duration of surgery
as an objective measure of intended outcome. One
study found a shorter operating time compared with
nonembolized patients in other published reports
[8], and three trials found no benefit from preopera-
tive embolization [42, 51, 52].
Immunologic response was also evaluated as a
measurement of intended outcome. Wallace et
al. [47] suggested that angioinfarction of the tumor
may result in release of tumor antigens, resulting in
enhanced immunity against the tumor, and also that
embolization prolonged survival in a selected group
of patients. Although several reports showed dis-
torted immunologic homeostasis after renal artery
embolization, there was no conclusive evidence that
embolization provided immunotherapeutic benefits
in the management of advanced renal cell carcinoma
[36, 40, 46]. In one study, patients with metastatic
renal cell carcinoma who were treated with emboli-
zation and nephrectomy had a longer survival than
patients who underwent embolization only [35]. In
a more recent study not included in the review by
Kai.vian and Varenhorst, preoperative emboliza-
tion resulted in improved survival after nephrec-
tomy: the overall 5- and 10-year survival rates were
62% and 47%, respectively, for 118 patients emboli-
zed before nephrectomy and 35% and 23%, respec-
tively, for a matched group of 116 patients treated
with surgery alone (p = 0.01) [12]. But this optimism
is not shared by the experience of other researchers
[11,41,42].
Palliation of symptoms in nonoperable patients
was also included in some outcome analyses. The
details of symptoms and therapeutic effects of renal
artery embolization are generally lacking, but stud ies
generally reported that hematuria, pain, and paraneo-
plastic symptoms were alleviated. In one study, severe
hematuria resolved in 11 of 14 patients, and incom-
plete embolization of the tumor blood supply from
parasitized lumbar arteries resulted in persistent
hematuria in 3 of 14 patients [11]. In another study,
malignant hypercalcemia resolved after emboliza-
tion [10]. Kalman and Varenhorst concluded that
a small group of patients with specific, tumor-related
symptoms may benefit from embolization. However,
the palliative effect of embolization cannot be evalu-
ated from the available data, and the effectiveness of
the procedure awaits validation.
The most common side effect of embolotherapy
is the post-embolization syndrome, which consists
of low-grade fever, pain, nausea, and vomiting that
start shortly after embolization and may last sev-
eral days [32, 39, 47, 49]. These symptoms are often
self-limiting and require only supportive therapy.
Although solid evidence was not provided, some
studies suggested that ablation of tumors with etha-
nol may result in a lower frequency of nausea and
vomiting and an overall milder post-embolization
syndrome than ablation of tumors with other par-
ticulate embolic agents will [8, 21, 38]. More serious
complications have been reported as a result of non-
target embolization of the large bowel, spinal cord,
contralateral kidney, or gonadal artery [23-26].
Contrast-induced nephropathy, renal abscess, and
hypertension have also been reported [47]. In their
initial description of the technique, Rabe et al. [22]
recommended the use of broad-spectrum antibiotics
before and after embolization to prevent superinfec-
tion of necrotic tumor. Many reports lack specifics,
but the need for prophvlactic antibiotics does not
seem to be universally accepted. In 1985, Lammer
et al. [24] reported a 9.9% overall complication rate
in 121 renal tumor embolizations and a mortality
rate of 3.3%. The most common complications in
this series were renal failure and nontarget emboli-
zation. The complication rate was four times higher
in the palliative embolization procedures than in
the preoperative embolizations. The authors attrib-
uted this discrepancy to the larger embolized tumor
mass and the severely impaired health of patients
who underwent palliative embolization [24]. A
decade later, Bakal et al. [7] reported a puncture
site hematoma as the sole complication in a group of
24 patients who underwent preoperative emboliza-
tion. It appears that with advancements in technol-
ogy and experience in embolotherapy, complication
rates have decreased substantially.
In a recent review of our database, we identified
30 consecutive patients (20 males, 10 females) with a
mean age of 65 years (range, 42-85). who underwent
embolization and surgical resection of their renal
gery, tumor thrombus was removed from IVC in 25
patients (83%) and from the right atrium in 3 patients
(10%). The surgeons reported substantial bleeding
from venous collaterals in 8 patient'; (27%), marked
inflammatory response around kidney in 6 patients
(20%), and ascites in 1 patient (3%). Median blood
transfusion requirement was 2 units of packed red
blood cells. Mean tumor size was reduced tol0.5 cm
after resection (ji-value, 0.003). In 3 patients (10%)
a significant reduction in size of IVC thrombus was
noted during surgery.
16.1.4.2
Embolotherapy for Angiomyolipoma
Nelson and Sanda [13] summarized contempo-
rary advances relevant to the clinical management
of renal angiomyolipoma. Among other factors,
the authors cited refinement of embolization and
partial nephrectomy techniques as major develop-
ments in the management of these benign tumors.
Their review of the literature identified 24 reports
[22, 27, 31, 54-74] of a total of 76 patients regard-
ing therapeutic embolization for angiomyolipoma
(Table 16.4). The most common indication for embo-
lization was acute hemorrhage. Other indications
were symptomatic tumors inpatients who were poor
surgical candidates or had limited renal reserve
and asymptomatic tumors for which prophylactic
treatment was deemed appropriate. Post-emboliza-
tion syndrome was recorded for 85% of patients,
other complications were reported in 10% of cases
including renal abscess (5%) and pleural effusion
(3%). Over a median follow-up of 23 months (range,
Embolotherapy for Organ Ablat
0-204 months), 17% of patie
Corns or hemorrhage that rei
Cion or surgery.
16.1.5
Future Directions
recurrent symp-
'epeat emboliza-
Preoperative and palliative embolization of renal cell
a may benefit a large number of patients,
city of scientific evidt
However, be
the techn
although embolization
for acute hemorrhage :
lipoma, it is not widely i
underutilized. Similarly,
s an accepted treatment
patients with angiomyo-
treat asymptomatic
patients with this condition. Patient selection, tech-
nical details, expected complications, and outcomes
all remain unclear at this time. Prospective clinical
trials and randomized clinical trials are necessary
to evaluate the true value of embolotherapy in the
management of renal tumors.
Embolotherapy in Management
of Hypersplenism
16.2.1
Introduction
Surgical removal or transcatheter ablation of splenic
parenchyma is often performed for the management
of hypersplenism, a pathologic condition in which
there is increased pooling or destruction of the
corpuscular elements of the blood by the spleen,
resulting in reticuloendothelial hyperplasia [75].
Hypersplenism may be seen in many disorders,
including cirrhosis with portal hypertension [76,
77]; hematologic abnormalities such as idiopathic
thrombocytopenic purpura, thalassemia major,
and hereditary spherocytosis [78-82]; and diffuse
splenic infiltration from primary malignancies
such as leukemia and lymphoma [83-86]. Signs of
hypersplenism include splenomegaly, thrombocyto-
penia, leukopenia, and anemia, and symptoms may
include abdominal discomfort, pain, respiratory
distress, and early satiety [87, 88]. Removal of func-
tional splenic tissue may also improve hematologic
abnormalities related to bone marrow suppression
from systemic chemotherapeutic and immunosup-
pressive agents so that optimal doses of such medi-
cations can be maintained [88-90].
Total splenectomy may be an effective treatment
for hypersplenism, but it impairs the body's ability
to produce antibodies against encapsulated microor-
ganisms and predisposes patient to sepsis [91]. Par-
tial splenectomy has been proposed as a way to avoid
this life-threatening complication [92, 93]. Despite
surgery (total or partial splenectomy), the patient's
condition for which the operation is performed may
relapse, resulting in the need for a second opera-
tion or additional transfusions [81, 92-96]. Other
patients may not be considered surgical candidates
because of their underlying medical condition and
During the past three decades, splenic arterial
embolization has been advocated in the nonopera-
tive treatment of patients with these difficult clini-
cal scenarios by intentionally infarcting splenic
tissue and reducing its consumptive activity. In
1973, Maddison [97] reported the initial clinical
experience of splenic artery embolization, but severe
complications that resulted from complete splenic
infarction prevented acceptance of the technique as
a viable treatment option. Since this initial descrip-
Table 16.4. Results o: embdixiiei.ipv :or iiiigioiv.yoliponia
Reference No. of % Complici
% Recurrent % Repeat
%Sn
rj>ery
Median, fol
svmpioms or emboliZLidc
hemorrhage
(mos.) frai
60 40
D
13 13
20
IS (0-29)
24 (12-4?)
24 (3-96)
29
20
15 (1-204)
28 (8-72)
20 \1-S4i
8 4
27
5 (0-60)
Kess
US [54]
R[S5]
Lee [27]
Hamlin [56]
Has [57] 14
Soulem [58] 5
Others [22,31.59-74] 25
(few
Totals
Fioir.: N:-:i.:;
a [i 3] : punted wirh pe:
tion, many authors have advocated incomplete or
partial splenic embolization (PSE), a method by
which a portion of the splenic parenchyma is left
viable, thus preserving the spleen's immunologic
function and limiting complications while still
managing the underlying condition [78-82, 87-90,
98, 99]. PSE has also been advocated as a preopera-
tive tool to improve the safety of and reduce intra-
operative blood loss during open or laparoscopic
splenectomy [100-103].
16.2.2
Anatomic Considerations
The splenic artery supplies the spleen
substantial portions of the stomach and pa
[104]. The splenic artery courses superior and ante-
rior to the splenic vein along the superior edge of
the pancreas. Near the splenic hilum, the artery
usually divides into superior and inferior terminal
branches, and each branch further divides into four
to six segmental intrasplenic branches. The supe-
rior terminal branches are usually longer than the
inferior terminal branches and provide the major
splenic arterial supply. A superior polar artery usu-
ally arises from the distal splenic artery near the
hilum, but it may originate from the superior ter-
minal artery. The inferior polar artery usually pro-
vides the left gastroepiploic artery, but it may arise
from the distal splenic or inferior terminal artery.
The left gastroepiploic artery then runs along the
greater curvature of the stomach. Numerous short
gastric branches arise from the terminal splenic or
left gastroepiploic artery to supply the gastric cardia
and fundus. In addition, the splenic artery has many
branches to the body and tail of the pancreas; the
largest of these are the pancreatic magna and dorsal
pancreatic artery. When PSE is considered, knowl-
edge and visualization o\ these arteries is essential
to reduce the risk for nontarget embolization.
16.2.3
Technical Considerations
PSE refers to partial obliteration of the peripheral
intrasplenic vascular bed by injection of embolic
material through the angiographic catheter placed
within the splenic artery. This technique evolved
as initial attempts to treat hypersplenism by proxi-
mal splenic arterial occlusion proved unsuccessful.
Response failure was attributed to the abundant
collateral circulation from the short gastric and
gastroepiploic arteries that reestablish the blood
supply to the spleen around the occluded segment
of the splenic artery [105-107]. Proximal arterial
occlusion, although ineffective for management
of hypersplenism, is a useful technique for reduc-
ing intraoperative blood loss in thrombocytopenic
patients undergoing splenectomy [108, 109].
Because of the need for more enduring and effec-
tive hemodynamic and hematologic responses, total
infarction of the spleen was performed with autolo-
gous clots or particles in single or staged procedures
[83, 97, 110, 111]. However, the widespread use of
this technique was limited because of the severity
and high incidence of complications such as splenic
abscess, splenic rupture, septicemia, splenic vein
thrombosis, and unremitting bronchopneumonia
[83, 110-115]. Several mechanisms may cause com-
plications after complete infarction of the spleen:
induced immunocompromised state of the patient,
predisposition of anaerobic bacterial growth within
the hypoxic ischemic tissues, introduction of exog-
enous bacteria through the angiographic catheter
or embolic agents, and contamination of the devas-
cularized splenic tissue with organisms originating
within the intestines by retrograde portal blood flow
[83,106,112, 116, 117].
Hemodynamic and hematologic responses and the
severity of complications correlate with the amount
of splenic tissue that is infarcted after embolization
[110]. Therefore, PSE has been advocated to reduce
complication rates after splenic infarction. Abla-
tion of more than 80% of the splenic mass has been
reported, but most authors have attempted to embo-
lize60%-70% of the parenchyma [115, 118-120]. This
amount of embolization allows for reduced seques-
tration and destruction of the blood elements while
maintaining the spleen's immunologic function and
preserving antegrade flow within the splenic vein.
Spigos et al. [112] adopted a strict protocol that
resulted in a remarkably low number of complica-
tions. The protocol included broad- spectrum anti-
biotics started 8-12 hours before the procedure and
continued for 1-2 weeks, local antibiotics (such
as gentamicin) suspended in the solution used to
deliver the particulate embolic agents and admin-
istered through the angiographic catheter, strict
attention to sterility (whole-body povidone-iodine
bath or wide surgical scrub at the site of catheter
insertion), selective catheterization with the cath-
eter tip beyond pancreatic branches, effective pain
control with narcotics or epidural anesthesia for
48 hours (which prevents the splinting that may
!-_ it.iL>-- "■ I. Mil e:apv :'.:■[■ Organ Ablution
lead to pulmonary co mp lie at ions), and avoidance of
overembolization. A Pneumovax vaccine was also
administered before the procedure to help prevent
pneumococcal infection.
More recently, Harked et al. [99] evaluated the
effect of PSE where only 30%-40% of the splenic mass
was ablated and found that the reduced infarction
volume still led to increased platelet counts, albeit
the increase was less impressive in those patients
than in patients in whom 70%-80% of the spleen
was ablated. However, their technique also resulted
in significantly lower morbidity. Therefore, a more
conservative embolization procedure with lower
complication rates may be prudent, and a second
embolization can be performed if necessary.
PSE can be performed by two methods. In one
approach, a few distal branches of the splenic
artery are selectively catheterized and embolized
to complete stasis, and several other branches are
left untreated (Fig. 16.3). Parenchymal phase of
angiogram may be used to estimate the volume
of remaining viable splenic tissue. Additional
branches can be catheterized and embolized
until the desired effect is achieved. In the second
method, the working catheter tip is placed more
proximally in the main splenic artery but beyond
the origin of major pancreatic branches. Embolic
particles are injected until the parenchymal blush
is reduced nngiographicully to the desired amount.
Contrast-enhanced CT scan may be used for follow
up purposes (Fig. 16.4).
In patients undergoing splenectomy, distal or
proximal splenic arteries can be completely occluded
to reduce the risk of intraoperative hemorrhage.
After the embolization, if patients have thrombocy-
topenia, a femoral arterial closure device may help
promote hemostasis at the puncture site. Patients
commonly experience fever, leukocytosis, and ele-
Fig. 16.3a-c. A 47-year-old woman with locally advanced
pancreatic carcinoma and thrombocytopenia, precluding
fuithe: c:".cniC'th.er.iL , y, was interred for p;'.:u.;l splenic embo-
lization. Pre-embokzittion I'.rtenogr.tm iaj shows normal
splenic artery anatomy. The superior splenic artery (b)
was selectively o.\ the ten zed and embolized using particles
i range. .!00-?00 microns i. Posi-emboiizalion arteriogram :. c:
shows complete occlusion of the s : ape:ior splenic artery. One
month after emholizauon, her platelel count was greater than
400,000/mm 3
D. C. Madoff et aL
Fig. 16.4a,b. A 4S-vei'.r-old man with pancreatic cancer pre-
sented with persistent neutropenia and thrombocytopenia.
Patient was referred for pai;ial splenic embolization (PSE i in
nil ir.lempi io increase white b I ::■.:■ .". cell ami clatelei coiinis
prior to additional chemotherapy. Pre-embolization axial
'".'.' image or I :". e- ahdomr:'. iai - : .'.ows splenomegaly. i."T sea:;
performed 4mon:hs arler PSE !l>j shows massive necrosis of
splenic parenchyma. VVi:hin _ week:, of partial splenic embo-
I. ;:.:i..: i"i. i.'.e pkie.ei c- '.'.;":; ;:■ a maa/.ed i.v l ' , , l 'i , '»''/iaia : :
vated serum amylase levels, but these complications
are transient.
The embolic agents most commonly used for
splenic ablation are Gelfoam pledgets and poly-
vinyl alcohol particles. Yoshioka et al. [105] also
showed excellent increases in platelet counts when
coils were placed within the intrasplenic branches,
and Hickman et al. [108] successfully used Gel-
foam, polyvinyl alcohol particles, and coils alone
or in combination for preoperative embolization. In
animal studies, additional materials that have been
used for this purpose are absolute ethanol [121, 122],
microfibrillar collagen [123], tissue adhesives [124],
balloon catheters [125], silicone particles [126], and
others [127], but none of these agents have been
widely accepted for use in humans.
The techniques developed and used at different
centers vary greatly, but some general recommen-
dations can be made here. Pre-procedure antibi-
otics are highly recommended. Povidone-iodine
baths are not commonly used, but careful attention
to sterile preparation is warranted. Embolization
can be performed through the diagnostic catheter
placed in the splenic artery only if the catheter tip
can be advanced beyond the origin of major pan-
creatic branches; a coaxial system with the use of a
micro catheter often facilitates catheterization of the
appropriate branches. Adequate pain control after
the procedure with the use of patient-controlled
analgesic pumps is warranted to minimize the sever-
ity and possibly duration of the post-embolization
syndrome and to decrease the risk of pulmonary
complications (such as atelectases and pneumonia).
Similar to complete splenic arterial emboliza-
tion, PSE is prone to complications and adverse
effects, but PSE is much better tolerated than com-
plete splenic ablation. In addition to those men-
tioned above, patients might develop pancreatitis
(likely a result of nontarget embolization of dorsal
pancreatic and pancreatic magna arteries), pleural
effusions requiring thoracentesis, paralytic ileus, or
the post-embolization syndrome consisting of fever,
leukocytosis, and abdominal pain [1 1 (| ],
After PSE, the spleen retains its ability to regener-
ate. Kumpe et al. [120] found substantial regeneration
of splenic tissue in 9 of 11 patients despite 70%-80%
embolization, as visualized on Tm-99m sulfur colloid
liver-spleen scans performed 4 to 16 months later. In
contrast, Watanabe et al. [128] reported that PSE of
80% or more resulted in initial increases in spleen
size followed by substantial and stable reductions by
4 months. Despite these conflicting results, a repeat
PSE procedure can be performed with similar effec-
s should symptoms recur [98].
16.2.4
Results
Few studies have compared splenectomy with PSE
in a randomized, prospective fashion. In a series
by Mozes et al. [118], 53 patients who were to later
undergo renal transplant with aznthioprine immu-
nosuppressive therapy (which causes leukopenia
and thrombocytopenia) were randomly assigned to
a splenectomy ai'onp (25 patients) or a PSE group (28
patients). For patients in the PSE group, a mean of
Embolotherapy for Organ Ablat
65.4% ± 16.6% of the splenic mass was ablated. The
early postoperative morbidity rate and the duration
of hospital stay were similar in the two study groups.
Abscess and splenic rupture were not encountered.
The two cases of severe pancreatitis resulting in
death occurred in the splenectomy group, and one
death from pneumococcal pneumonia occurred
3 months after PSE. Equivalent numbers of renal
transplantation were carried out in both groups
and resulted in similar long-term (2.5-4.0 years)
graft survival (60% vs. 66%) and long-term patient
mortality. However, splenic regeneration occurred
in most patients after PSE, and doubling of splenic
parenchyma was seen in 40% of them. As demon-
strated in this study, PSE may be an effective alterna-
tive to splenectomy, especially for patients who are
not suitable surgical candidates.
Numerous retrospective studies have demon-
strated that PSE is an effective short-term therapeu-
tic alternative to splenectomy for a wide spectrum
of patients with hypersplenism [77,78,80,82,88-90].
Kimura et al. [80] reported the results of initial and
repeated PSE in patients with chronic idiopathic
thrombocytopenic purpura. Thirty-nine patients
underwent initial PSE, and 12 underwent a repeat
PSE. The therapeutic effects of initial and repeat PSE
were classified as complete response if the patient's
platelet count rose to more than 100,000/mm 3 with-
out steroids 1 year after the initial or repeat embo-
lization, as partial response if the platelet count
increased by 50,000-100,000 under similar circum-
stances, or as no response. Twenty patients (51%)
responded to the initial PSE (11 complete response,
9 partial response) with signilieantlv higher peak
platelet response (p = 0.029). Differences between
responders and nonresponders in terms of age, sex,
lowest platelet count, and steroid response before
PSE were nonsignificant. Of the 11 patients with
complete response (median follow-up, 58 months;
range 21-156 months), one relapsed after 32 months
and underwent repeat PSE. Of the 9 patients with
partial response, four maintained a platelet count
of more than 50,000/mm 3 without relapse during a
median follow-up period of 73 months (range, 14 to
42 months), and five relapsed after a median follow-
up period of 34 months (range, 15-123 months).
Repeat PSE resulted in four partial responses and
one no response. However, in 6 of 19 patients who
had no response to the initial PSE (median follow-up,
8 months; range, 3- 22 months), repeat PSE elicited
only one partial response. The 51% remission rate
was maintained by means of repeat PSE for a median
follow-up of 76 months (range, 14-147 months) after
the initial PSE. Kimura et al. concluded that PSE
combined with repeat embolization may be an
effective alternative to splenectomy in patients with
chronic idiopathic thrombocytopenic purpura.
Palsson et al. [129] reviewed 26 severely ill
patients (median age, 63.5 years) who were treated
with PSE a total of 52 times, mainly because of
bleeding esophageal varices and thrombocytope-
nia. The mean hemoglobin values, leukocyte counts,
and platelet counts increased significantly after
PSE, and the frequency of bleeding episodes from
esophageal varices was statistically significantly
reduced. As defined by the authors, the integrated
PSE effect was judged as improved in 19 patients,
unchanged in five, and worse in two. Median sur-
vival time was 50.5 months (range, 0.5-272 months).
Complications consisted mainly of fever, atelectasis,
and abdominal pain, although two patients died of
PSE-related complications. Thus, a standardized
and graded PSE is reasonably safe even in patients
with advanced disease in whom it is hazardous to
perform splenectomy. Palsson et al. concluded that
PSE maintains long-term effects on hematologic
parameters, esophageal variceal hemorrhage, and
may substantially improve patients' diniatl statu',.
Nio et al. [130] published a retrospective study
in which 41 PSE procedures were performed in 36
children with liver disease and thrombocytopenia
resulting from hypersplenism. The average volume
embolized was 70.1%, and the mean follow-up was
71 months (range, 20 days-182 months). Eleven
patients (30.6%) had recurring thrombocytopenia
(defined as fewer than 100,000/mm 3 ). There were no
significant differences in the volume embolized or
platelet count before PSE between the patients with
and without recurring thrombocytopenia. However,
the peak platelet counts after PSE was significantly
lower in the patients with recurring thrombocy-
topenia (p = 0.0091). In 17 of 24 survivors who did
not undergo liver transplantation, platelet counts
remained normal throughout the follow-up period.
Hematologic indices improved in all 36 patients
after PSE, and its long-term efficacy was shown in
70% of the:
16.2.5
Future Development and Research
External beam radiation therapy is an alternative
treatment for patients with splenomegaly [131-135].
Similarly, transcatheter arterial brachytherapy
using yttrium-90 microspheres has been reported
D. C. Madoff et al.
[136, 137]. At the time of this writing, the cost asso-
ciated with intraarterial brachytherapy and the
complexity of the delivery system discourage its
widespread use. When intraarterial bra chy therapy
becomes more widely available, further investiga-
tion of its usefulness in patients with hypersplen-
ism may be warranted. Thermal ablation therapy,
which has received considerable attention over the
last decade, has been used to treat patients with
hepatic malignancies, small renal cell carcinoma,
and lung tumors [138, 139]. More recently, radiofre-
quency ablation has been proposed as an alternative
treatment for hypersplenism [140]; the safety and
usefulness of this approach remains to be carefully
evaluated in clinical setting.
16.3
Conclusion
Embolotherapy for organ ablation, as highlighted
in this chapter for treatment of patients with renal
tumors and hypersplenism, was developed in the 1970s
and enjoyed a period of intense activity over the next
two decades. During that period, numerous articles
describing single-center experiences with small series
of patients appeared in the medical literature. Retro-
spective studies of small series of cases demonstrated
the safety and potential benefits of embolotherapy for
organ ablation in selected patients. During the same
period, technological advancements have elevated the
fields of angiography, vascular catheterization, and
Table 16.5. Catheters and cmbokc agents used for organ
Renal Artery Embolization
Abdominal aortogram
Pigtail catheter, 5 Fr Cook, Bloomingtc
Selective renal arteriogram
C2 Cobra Visceral, 5 Fr Cook, Bloomingtc
Sos Omni Selective (2), 5 Fr Angiodyn amies, C
Occlusion balloon catheter, 5 Fr
Subselective renal arteriogram
Renegade HI-FLO, 3 Fr
Embolic agents
Dehydrated alcohol
EmboGold microspheres
Contour.SE Microspheres
Absorbable Gelatin Sponge
Splenic artery embolization
Selective splenic arteriogram
C2 Cobra Visceral, 5 Fr
Sos Omni Selective (2], 5 Fr
Subselective splenic arteriogram
Renegade HI-FLO, 3 Fr
Embolic agents
Absorbable Gelatin Sponge
EmboGold Microspheres
Contour.SE Microspheres
Boston Scientific Medi-Tech, Natick, MA
American Regent, Shirley, NY
Biosphere Medical, Rockland, MA
Boston Scientifrc, Natick, MA
Ethicon, Somerville, NJ
Cool., R!oomiag:on. ;i^
Angiodyn amies, Queensbury, NY
Boston Scientific Medi-Tech, Natick, MA
Ethicon, Somerville, NJ
Biosphere Medical, Rockland, MA
Boston Scientific, Natick, MA
Fig. 16.5. A simp.e and r:se:iil algo-
rithm for planning embolization of
renal tumors. Interventional radiolo-
gist should be familiar with various
embokc .:genls including eikriio. and
solid particles and different methods
for delivery of these agents. Neverthe-
less, die algorithm may be modified to
suite individual expertise and available
embolic agents
Embolotherapy for Organ Ablat
embolotherapy to new heights. Table 16.5 provides a
short list of supplies currently used for embolotherapy
at our institution. A simple algorithm for embolization
of renal tumors is also suggested (Fig. 16.5). In this era
of evidence-based medicine, advanced embolotherapy
techniques warrant re evaluation and validation in the
management of renal tumors and hypersplenism.
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17 Research and Future Directions
in Oncology Embolotherapy
Introduction 221
Advances in Chemotherapeutic Agents 21
.1 Convention Li I Chtiviccherapeulic Agents 1
2 Novel Drug Regimens 222
Update on Current Use and Development
of Embolic Agents 223
.1 Ethiodol 223
1 Gelfoam 224
.3 Polyvinyl Alcohol (PVA) Particles 225
A N-Butyl-2-Cyanoacrylate 225
.5 Spherical Eincojc Agents 22"
.5.1 Plain Spherical Agents 226
.5.2 Drug-Loaded Embolic Agents 22S
Advance m^:'.:? in E:y.:iojza:io:' Technique
Conclusion 229
References 230
17.1
Introduction
Oncology embolotherapy consists of a catheter-
based group of treatments where embolic agents are
intravascularly directed to target cancerous lesions.
This group of therapies is mainly represented by
transcatheter arterial chemoembolization (TACE)
for primary and metastatic hepatic lesions; how-
ever, oncology embolotherapy has been applied
beyond liver for palliative treatment of bone, pul-
monary, renal, oral cavity or anterior oropharynx
lesions [11, 29, 30, 71]. The underlying principle for
E.Liapi.MD
The Russell K. Moi ga:'. I 'epai^meni '.■:' Radiology and Radio-
iogicul Sciences, Johns Hopkins Medical l:vs:iluiions, Balti-
more MD, USA
J.-F. H. Geschwind, MD
Associate Professor ■ 'I" Had [.:■;■ >gv. S.ngeiv j.i'.d Oncology, Divi-
sion of Vascular and Intervention.;! Radiology, 600 N Wolfe
Street, Blalock 545 Baltimore, MD, 21287, USA
the procedure is selective and precise delivery of
high doses of chemotherapeutic agents to malig-
nant hepatic lesions, so as to achieve local tumor
control, while minimizing systemic toxicity. While
exploiting the well-known arterial blood supply of
malignant hepatic lesions, oncology embolother-
apy involves the infusion of chemotherapeutic and
embolic agents.
In practice, despite its promising concept of
design, TACE has not shown yet to be as effective
and potent as in theory. Several challenging obsta-
cles that have not been exceeded yet include chemo-
therapeutic dose-limiting toxicity, development of
mechanisms for drug resistance and tumor revas-
cularization. Moreover, the techniques and agents
used for intra-arterial treatment of primary and
metastatic liver cancer are very heterogeneous. This
hinders a more systematic approach and interpreta-
tion of the results of clinical trials as well as imple-
mentation of meta-analyses.
Despite its heterogeneity and limitations, trans-
catheter arterial chemoembolization has gained wide
acceptance over the past 20 years and is currently
considered as the mainstay therapy for unresectable
primary and metastatic liver cancer [64, 67]. Recent
advances in infusible drug regimens, embolic agents
and embolization design, as wellas the positive results
of two recent randomized controlled trials and a
meta-analysis, have boosted investigators' optimism
to further develop this method of local tumor control
[7, 38, 39]. The extent of tumor necrosis after chemo-
embolization has been reported to range from 60%
to 100% [58]. However, these data need to be further
supported by conducting prospective randomized
clinical trials, with use of standardized interventional
oncologic protocols. Moreover, adequate knowledge
on the molecular basis of hepatic tumorigenesis may
optimal treatment of primary
ancer. New developments and
i hepatic oncology embolo-
imalgamation of its evolution-
with future trends in chemotherapeutic
agents, embolic agents and embolization techniques.
and metastatic liver c
research activities o:
therapy represent a
E. Liapi and J.-F. H. Geschwind
Following, we present a comprehensive approach to
recent advances on hepatic embolotherapy. Advances
on radioactive microspheres embolization are not
included, as they are thoroughly discussed inaprevi-
Advances in Chemotherapeutic Agents
17.2.1
Conventional Chemotherapeutic Agents
Currently, there is no good evidence for the best
chemotherapeutic agent. A number of chemothera-
peutic cocktails have been used for chemoemboli-
zation in the past decade, and controversy persists
regarding the selection of the most potent of these
drugs. A large variety of drugs including mitomy-
cin C, doxorubicin, epinibicin, cisplatin have been
used with TACE. The most common chemothera-
peutic drug used as a sole agent is doxorubicin,
whereas the combination of cisplatin, doxorubicin,
and mitomycin C is the most common combination
drug regimen for treatment of HCC [6]. All of these
drugs exhibit preferential extraction when deliv-
ered intra hepatic ally and they can achieve favor-
able tumor drug concentration with concurrent low
systematic drug load. Despite their favorable and
high intratumoral concentrations, most random-
ized controlled trials have failed to demonstrate
advantage of one agent over another [51]. In one
study, cisplatin was shown to be more effective than
doxorubicin as a single agent against HCC; however,
this improved effectiveness could not be correlated
with improved survival [9]. Recent data suggest that
injectable volumes of chemotherapy and long-term
arterial patency were improved by embolizing the
tumor-feeding vessel(s) only after the entire dose
of chemotherapy had been delivered [20]. In our
institution, a standardized regimen of chemothera-
peutic agents, based on the Hospital of the Univer-
sity of Pennsylvania protocol, regardless of tumor
type, is currently used. This regimen comprises of
cisplatin 100 mg (Bristol Myers Squibb, Princeton,
NJ), doxorubicin 50 mg (Adriamycin; Pharmacia-
Upjohn, Kalamazoo, MI) and mitomycin C 10 mg
(Bedford Laboratories, Bedford, OH) mixed in 10
ml of water-soluble contrast medium (Omnipaque;
Winthrop Pharmaceuticals, New York, NY). This
cocktail is then mixed with an equivalent volume
oflipiodol.
17.2.2
Novel Drug Regimens
Advances in the knowledge of the molecular patho-
genesis of HCC and hepatic tumor igenesis have led to
the testing of some novel cytostatic agents that may
interact upon some disrupted pathways. Among their
significant properties is their ability to overcome drug
resistance, inhibit angiogenesis and limit chemother-
apeutic dose-related toxicity. Phase I/II/II1 studies are
currently being conducted to explore whether anti-
angiogenesis agents, inhibitors of growth- factor- sig-
naling and cell cycle enzymes, nonspecific growth
inhibitory agents, specific ;.i unionists of HCC tumor
markers, and a nt i- inflammatory agents, may have a
role in the treatment of liver cancer [8].
Among those agents, bevacizumab (Avast in,
Genentech Inc., San Francisco, CA), a humanized
monoclonal antibody that binds vascular endothe-
lial growth factor (VEGF) and prevents its interac-
tion to receptors on the surface of endothelial cells,
has been recently added to the triple chemoemboli-
zation cocktail for patients with primary and meta-
static liver cancer. A recent pilot study, in selected
HCC patients undergoing TACE who additionally
received intravenous bevacizumab, showed encour-
aging results with good drug tolerance and pro-
longed disease control [4]. Currently, there are two
phase II trials evaluating the safety and efficacy of
bevacizumab in patients with primary and meta-
static unresectable liver cancer [47, 48]. The com-
bination of bevacizumab with this TACE regimen
seems challenging, as the formation of new blood
vessels may effectively be reduced while the targeted
tumor may maintain high cytotoxic chemothera-
3-Bromopyruvate (3-BrPa) is another example
of a drug disrupting a metabolic pathway, which
has been recently tested via transcatheter infusion.
3-BrPa is a hexokinase II specific inhibitor, which
potently abolishes cell ATP production via the inhi-
bition of glycolysis [19]. Preliminary experiments on
the rabbit VX-2 tumor model for liver cancer with
direct intraarterial infusion of 3-BrPa showed very
specific necrosis of the implanted lesions [19, 21].
Additionally, intraarterial injection did not affect
the viability of surrounding normal liver tissues, nor
damaged the animals' major tissues during systemic
infusion [19]. The mechanism of innate resistance of
normal cells against 3-BrPa treatment has not yet
been clarified, though it might be related to the dif-
ference of hexokinase II expression levels between
normal and malignant cells [17].
Rr? ■?;'.: ch .iiid Future Din
u Oncology Embdcdier.ipv
Recombinant adenoviral vectors, such as those
expressing recombinant b-galactosidase or human
hepatocyte growth factor, soaked in gelatin sponge
pledgets, have been recently tested for transcatheter
delivery in canines [53]. The intratumoral injec-
tion of oncolytic adenovirus seems to be a promis-
ing approach for the treatment of tumors resistant
to other modalities, but its intra-arterial infusion
warrants additional research. To date, the pub-
lished clinical experience with these agents has been
almost exclusively limited to intratumoral injection
on Phase I and II studies [62, 63].
The ideal chemotherapeutic agent for transcathe-
ter treatment of primary and metastatic liver cancer
is yet to be developed. This agent should combine
effectiveness against the tumor and reduced toxicity
to the normal or cirrhotic liver. In the near future,
some of the above novel drugs are expected to
enter the clinical arena and be prospectively tested,
whereas some of the currently used chemotherapeu-
tic agents such as doxorubicin, cisplatin and mito-
mycin C are expected to be tested in a more system-
atic and prospective way.
Update on Current Use and Development
of Embolic Agents
Several embolic agents have been employed over the
past two decades in order to enhance the effects of
transcatheter intraarterial drug delivery for hepatic
malignancies. These agents may produce different
effects on vasculature, resulting in permanent or
transient obstruction, by acting at different levels in
the arterial system. Usually, the injection of embolic
particles follows the injection of the chemotherapeutic
mixture, yet, some centers favor mixing the particles
in slurry with the chemotherapeutic drugs and oil
[20]. Embolization without chemotherapy (transarte-
rial embolization) has often been categorized as a form
ot chenioemboli^i.ition [?$]. Tins torn) ot emboloth cr-
apy has been occasionally described in the literature.
Arterial embolization alone has been investigated in
two randomized trials from Barcelona, which failed
to demonstrate a survival benelii [5, oS].
Despite the extensive research that is available on
hepatic embolization, the precise effects of emboli-
zation on tumor cells remain largely unknown. In
fact, recent data suggest that hypoxia, generated by
arterial embolization, may activate several genes,
including those for vascular endothelial growth
factor (VEGF) and hexokinase II, leading therefore
to compensatory angiogenesis and tumor growth
[24]. A direct link among the degree of emboliza-
tion, tumor hypoxia, and the stimulation of new
blood vessels has been suggested in a number of
recent studies. Kobayashi et al. found that blood
levels of VEGF were markedly increased in patients
who had been treated with embolization [27]. Poon
et al. reported that serum VEGF level was signifi-
cantly elevated in patients with HCC, and signifi-
cantly high serum VEGF levels were associated with
the absence of tumor capsule, the presence ofvenous
invasion and microsatellite modules, and advanced
TNM stage [56]. More recently, high serum level of
VEGF was found to be a predictor of poor outcome
after resection of HCC [57]. VEGF may also help in
predicting treatment response and monitoring dis-
ease course after chemoembolization [35].
From a different standpoint, similar simple obser-
vations have already confirmed the angiogenesis
theory by the formation of early revascularization
after proximal and temporary embolization induced
with gelfoam [20]. Moreover, it has been demon-
strated that proximal embolization of tumor-feeding
arteries in hepatic metastases with large particles or
coils may lead to immediate peripheral hepatic cir-
culation re constitution through collateral vessels.
It seems that the earlier the revascularization of the
tumor occurs, the more incomplete the necrosis will
be. An occlusion of more peripheral vessels gener-
ates a nearly complete tumor necrosis and current
trends in oncology embolotherapy seem to favor
distal occlusion. Gelatin sponge powder and pled-
gets and polyvinyl alcohol are the most commonly
used agents for chemoembolization [20]. Combina-
tions of ethiodol with other embolic agents have also
been reported for transcatheter use. Autologous clots,
coils and microcoils, or collagen have also been used
for oncology embolotherapy, but few reports have
assessed their efficacy [37]. An overview of charac-
teristics, current use and future prospective of some
commonly used embolic agents is next presented, as
well as an introduction to some novel embolic agents
(Table 17.1). The latter new category of new embolic
agents may lead to more accurate tumor targeting
and ultimately, improve patients' survival.
17.3.1
Ethiodol
This oily medium is a key ingredient to the chem
embolization procedure due to its unique combir
: 17.1. Size of emir oik ,i£e:v.~ irv.:. ::.■<: oncology em bolo therapy
Embolic Agents
P;i-:k-:ir Siz.
Polyvinyl alcohol foam
Gelfo-.im igc-kicii] sponge particles)
Tris-acryl gel micro spheiei iH::".'o.:go!ii and Embospher
Polyvinyl alcohol microspheres iContourSE)
Polyvinyl alcohol hydoigel :v..-.":o<pheres (Bead Block)
150-500 Li m
Microspheres) 40-1200 urn
45-1180 u.m
100-1200 u.m
E. Liapi and J.-F. H. Geschwind
tion of properties as a drug-carrier, tumor-seeking
and embolic agent. Since the observation that this
poppy seed oil accumulates preferentially in hepato-
cellular carcinoma (HCC) and other hepatic malig-
nancies, ethiodized oil or lipiodol (Ethiodol; Savage
Laboratories, Melville, NY) has been successfully
used as a suspension medium for chemotherapeutic
agents [13, 28, 45](), as a radiolabeling means by
labeling part of its iodine with 131 I to deliver targeted
radiotherapy, or as a plain embolic agent [2, 28, 50,
60]. In most cases, ethiodol is used along with a
chemotherapeutic cocktail and constitutes the basis
of most TACE procedures.
Although ethiodol has been used for more than
20years for chemoembolization of HCC and hepatic
metastatic lesions, the mechanism of its uptake by
cancer cells is not clearly understood. A biochemical
pump in the tumor cell wall recognizes ethiodol and
transfers the emulsion in the intracellular space,
and this pump is subsequently disabled by hypoxia,
thus trapping the ethiodol emulsion within the cell.
Ethiodol localizes in hepatic tumors when adminis-
tered via the hepatic artery, and is retained by HCC
for many weeks, even up to 1 year, while it is cleared
from normal or cirrhotic liver within 4 weeks.
When injected into the hepatic artery, it traverses
the peribiliary plexus to the portal veins resulting
in a dual embolization [69]. The amount of lipiodol
emulsion has been shown to proportionally depend
on the tumor size. However, hepatic parenchymal
damage or bile duct ischemia have been reported
by use of large amounts of lipiodol [12]. Individual-
ized adjustment of lipiodol dose, according to blood
supply pattern and tumor diameter as measured on
CT, has been recently suggested in a controlled ran-
domized trial [10]. The degree of lipiodol accumula-
tion at computed tomography has been shown to be
an independent indicator of better prognosis [44].
Labelingpart of lipiodol's iodine with 131 I attracted
researchers' interest early in the course of investigat-
ing lipiodol's potential for hepatic embolotherapy
[75].Intra-arterial 131 I-lipiodol has been successfully
used to treat inoperable hepatocellular carcinoma
and is well tolerated and effective in small tumors
(<5 cm) [42, 76]. Randomized studies have shown
that treatment with 131 I-lipiodol is at least as effec-
tive as but less toxic than chemoembolization and
that there is a significant increase in the survival of
patients presenting with an HCC with portal throm-
bosis [61]. Moreover, it may lead to a 50% reduction
in the recurrence rate 3 years after a resection [31].
Nevertheless, the administration of 131 I-lipiodol has
limitations related to radiation protection issues.
Following treatment with i3l I-lipiodol, patients are
not eligible for surgery for up to 4 weeks, due to the
relatively long physical half-life of m I (8 days) [31].
Another drawback is the required hospitalization of
up to 7 days, due to the high energy of the gamma-
ray emission of l3l I (365 keV) and its physical half-
life.
There have been various attempts to label lipi-
odol with other isotopes, in particular 90 Y, l88 Re
and recently g?m Jc [31, 77, 78] .Currently, the best
approach seems to be the labeling of a lipophilic
chelating agent with 188 Re, which is then put into
solution secondarily with the Lipiodol [77]. 188 Re is a
radionuclide with a higher energy of the beta-emis-
sion (2120 keV and 1960 keV for i88 Re versus 606
keV for 131 I) and its use, with its physical half-life
of 17 h, avoids most of the radioprotect ion problems
and allows for a shorter hospitalization, as well as
further dose escalations. Following 188 Re-lipiodol
treatment, patients are eligible for transplantation
after an interval of only 1 week. However, certain
problems remain, such as the relatively weak label-
ing efficiency, and further studies to determine the
maximum tolerated dose and potential hepatotoxic-
ity should be assessed.
17.3.2
Gel foam
Gelatin bioabsorbable embolic agents, in the form
of gelfoam sponge or powder, have been exten-
sively used as an intravascular embolization agent
for TACE. Gelatin sponge, which blocks circulation
transiently and is absorbed within 48-72 h, is cur-
rently the most commoiilv employed material. Gel-
atin sponge causes temporary vascular occlusion.
Reseitich .iiid Future Diri
n Oncology Entbolodierupy
with recanalization occurring in approximately
2 weeks [20]. When compared to powder, gelfoam
sponge provides a more proximal obstruction to
blood supply. However, proximal obstruction may
enhance the development of revascularization of
treated lesions through aberrant collaterals and
limit tilt 1 eftieacv ol Inrtlter embolization. On tile
other hand, gelfoam powder can induce ischemic
bile duct necrosis. Improved overall patient survival
rates with the addition of geltoam sponge to the lipi-
odol emulsion were initially described by Nakao et
al. in a retrospective study on 343 patients [46]. In
this study, no dose-response relationship was found
and based on these data, [he combination of lipiodol
and gelfoam sponge was further suggested for trans-
catheter treatment of hepatic malignancies. The use
of gelatin-sponge allows repetitive chemoemboliza-
tion procedures, which in some centers is desirable
[20]. Today, gelfoam is still widely used and new
applications of its use, such as its soaking in recom-
binant adenoviral vectors may shed new light in the
use of this traditional embolic agent [53].
17.3.3
Polyvinyl Alcohol (PVA) Particles
Polyvinyl alcohol (PVA) particles have been success-
fully used since 1974 as an intravascular embolic
agent and for many years, it has been considered
the standard embolic agent for TACE [68]. The earli-
est method of its preparation for use as an embolic
agent first involved its conversion into foam that
can absorb water and become readily compressible.
According to this preliminary method, PVA par-
ticles were prepared by scraping a compressed block
or by cutting off pieces, which were then filtered
through different sizes of sieves. Their irregular
shape, however, did not ensure uniformity of the
final compound, as large particles were likely to pass
through small holes depending on their orientation
during filtration. This problem created variability
in size and shape; however, later on, changes were
made to ensure improved uniformity.
Polyvinyl alcohol is considered to be a permanent
embolic agent because it is not biodegradable. The
histologic effects of PVA particles embolization have
been well documented, varying from inflammatory
and foreign body reactions to focal angionecrosis
of the vessel wall [36]. The duration of the vascular
occlusion induced by PVA is variable. Occlusions
may last for several months as a result of organiza-
tion of the thrombus, with recanalization attributed
Fig. 17.1. Polyvinyl alcohol piirdcles. Their irregulur slu;p
does not gu-.iriii'.iee precise wssel occlusion, l Courtesy of Bio
sphere Medical Inc.)
to thrombus resorption and angioneogenesis [36].
Unexpected and non-targeted embolization has
been reported, creating some uncertainty over their
use. In a study testing the effects of embolization
protocol on injectable volume of chemotherapy and
subsequent arterial patency, the type of chemoem-
bolization protocol rather than the type of embolic
material had a significant impact on the rate of
arterial recanalization or arterial patency [20]. Sur-
prisingly, the assumption that PVA particles result
in deeper penetration, when compared to gelfoam
pledgets, was not confirmed in this study [20].
17.3.4
N-Butyl-2-CyanoacryIate
This glue, first used for bleeding control, has been
successfully utilized for preoperative portal vein
embolization [15]. This adhesive, that polymerizes
on contact with blood and endothelium, does not
affect the peribiliary arterial plexus, and this prop-
erty led to the assumption that it can be used for
transcatheter arterial embolization [55]. Mixed with
radiopaque lipiodol, the polymerization time can be
prolonged to 10-15 s, depending on dilution. There-
fore, a more peripheral and permanent embolization
In an initial short report, patients with c;
hepatic metastases treated with a mixture of W-
butyl-2-cyanoacrylate/ethiodol, showed complete
and long-lasting relief of symptoms, with signifi-
cant decrease or normalization of levels of 5-HIAA
in the urine, and a reduction of metastatic tumor in
the liver [72]. Another study demonstrated prom-
ising results in the treatment of metastatic hepatic
E. Liapi and J.-F. H. Geschwind
insulinomas [73]. Other retrospective studies have
shown that TACE with use of cyanoacrylate and
lipiodol for unresectable HCC and neuroendocrine
hepatic metastases is feasible [41, 42]. Cyanoacrylate
was recently used in a retrospective study of patients
treated for unresectable HCC, combined with other
embolic agents without concurrent addition of che-
motherapy [59]. Still, this type of embolic material
is used for bland embolization and assessment of its
effectiveness compared to the use of other embolo-
therapy regimens is rather complicated.
17.3.5
Spherical Embolic Agents
tithe:
echm
sofa.
!S Of Ct
Investigati
mercially available embolic agents demonstrated
that novel embolic materials should possess a com-
bination of certain mechanical and physicochemi-
cal properties in order to maximize their efficiency
and minimize potential side effects. First, they
must be spherical in shape to allow for accurate
calibration, optimal and complete geometric vessel
occlusion. Spherical particles have a single dimen-
sion; moreover, depending on their size, they may
block tightly and gradually seal the vascular lumen,
whereas non-spherical particles produce a more
incomplete occlusion. Second, the particles must
not aggregate, which may lead to catheter obstruc-
tion and proximal arterial occlusion. Other desir-
able properties include unproblematic fabrication,
controlled deformability, good biocompatibility and
in vivo stability when mixed with chemotherapeutic
agents. Moreover, potential drug-loading combined
with sustained drug release seem to be very attrac-
tive properties that may lead to the establishment of
a new category of embolic agents and transform the
profile of oncology embolotherapy.
With the recent bloom in na no technology, sev-
eral types of microspheres have been developed [3].
Some of these new types of spherical agents, such
as polyvinyl alcohol and tris-acryl microsphi
are non-degradable, resulting in more permanent
occlusion. Others, such as gelatin, albumin, poly-
saccharides (dextran), starch, ethyl cellulose, and
poly-(D,L lact id e/glycos id e)- copolymer include a
resorbable component, and are not suitable for per-
manent vascular occlusion [18]. The optimal size of
these embolic agents tor chemoembolizationhasyet
to be established. Spherical embolic agents may be
categorized into plain (unloaded) and drug-loaded
(or drug-eluting) spheres.
17.3.5.1
Plain Spherical Agents
17.3.5.1.1
Tris-acryl Gelatin Microspheres
Tris-acryl gel microspheres were the first spherical
embolic agents to be commercially available [32].
Tris-acryl is an entirely synthetic, hydrophilic, and
nonresorbable material. It has been demonstrated
that this material produces non-toxic tissue reac-
tion, thus allowing absorption and cellular adhe-
sion [32]. Colored and non-colored tris-acryl gelatin
microspheres (Embogold and Embosphere Micro-
spheres; Biosphere Medical, Rockland, MA} are cur-
rently commercially available.
These microspheres are precisely calibrated,
spherical, hydrophilic, microporous beads made
of tris-acryl co-polymer coated with gelatin. They
come in defined range of sizes, ranging from 40 to
1200 |im in diameter. Their smooth hydrophilic sur-
face, deformability and minimal aggregation ten-
dency have been shown to result in a lower rate of
catheter occlusion and more distal penetration into
the small vessels [32]. Their efficacy has been evalu-
ated in several conditions, and when compared to the
standard polyvinyl alcohol particles (PVA) particles,
a deeper penetration and embolization of smaller
and more peripheral vessels may be achieved. This
distal embolization may limit the development of
any collateral blood supply. Also, in a study where
PVA particles and tris-acryl microspheres of similar
size were compared, the level of vascular occlusion
with calibrated tris-acryl microspheres precisely
correlated with particle size whereas the level of vas-
cular occlusion with PVA particles did not. Another
study has demonstrated that in embolized tumors,
7<ChrO
Fig.17.2. Embosphere microspheres. These tris-acryl gelatin
micro spheres are precisely c-.ihoi LUeJ. spheres!, hydrophilic.
microporous beads, i Oout tesy of Andy Lewis, biocompatibles,
UK, Ltd, Surrey, UK)
Research and Futu
n Oncology Embolorheiiipy
a great majority of occluded vessels were located
within the tumoral tissue, and vessels located out-
side the tumor were rarely occluded [33]. Interest-
ingly, the median diameter of the occluded vessels
located within the tumors was 210 u.m. However, the
authors avoided suggesting this number as a thresh-
old for the penetration, due to tumor vessel variabil-
ity and histological processing piikilK
Tris-acryl gelatin microspheres have be
to be stable in a standard chemoembolization solu-
tion and some centers have adopted their use [1].
Tris-acryl gelatin microspheres have been also
tested for compatibility with several chemothera-
peutic agents and can be mixed with carboplatin,
mitomycin C, 5-fluorouracil, or pirarubicin for
chemoembolization without any risk of harmfully
altering their morphology, dimensions, or geomet-
ric characteristics [70].
17.3.5. 1.2
Polyvinyl Alcohol Microspheres
A long track record of surety and efficacy of polyvi-
nyl alcohol led to the design of spherical PVA. PVA
(Contour SE Microspheres; Boston Scientific/Medi-
tech, Natick, MA) and PVA hydrogel (Bead Block,
Terumo Medical Corp., Somerset, NJ) are currently
available for transcatheter use.
Interestingly, PVA microspheres have been
observed to result in a very mild inflammatory
response [65]. This finding seems rather counterin-
tuitive and unexpected, considering the aggressive
inflammatory reactions that have been described
with PVA particles. Further studies, however, should
be conducted to assess whether this reduced intra-
vascular and perivascular inflammation may have
significant favorable clinical implications [65].
17.3.5.1.3
Other Types of Plain Microspheres
Poly-L -lactic acid (PLLA) microspheres have also
been tested for transcatheter delivery, but they are
biodegradable and tend to clog microcatheters, like
PVA particles. The diameter of these particles
can be changed according to the polymeriza-
tion time and therefore, various sizes of PLLA
microspheres can be prepared [74]. Loading of
these particles with neutron- activated radioactive
holmium 166 ( lt6 Ho) has also been tested for trans-
catheter administration in an animal HCC model
[49]. A recent study demonstrated that the Ho on
the surface of neutron-irradiated Ho-PLLA-micro-
Fig.17.3. Contour SE microspheres. PVA microspheres with
smooth, isydraphikc su: tace and sLuidnrdizc-d caliber of size.
(Courtesy of Andv Lewis. Riccom\-\i;iblcs. UK, Ltd, Surrey,
Fig.17.4. Bead Block (Tei
!-'VA hvdiogel microsphere
patibles UK, Ltd, Surrey, I
lino Mcdicil Coip.. ?i':-:eiset, Nl).
^ (Co : .'ircsy of A iid y i.eivjs, Biocom-
spheres is probably the reason for their poor sus-
pending ability in saline and that a pharmaceuti-
cally acceptable solvent (1% pluronic F68 or F127
in 10% ethanol) can be used for the formulation of
a homogeneous suspension, making these systems
feasible for further clinical evaluation [79].
Radiopaque microbeads made of polyaciyloni-
trile (PAN) hydrogel have also been evaluated in
vitro and invivo for transcatheter embolization on a
swine model showing potential for future use [23].
Superabsorbent polymer microspheres is another
example of nontoxic and non-biodegradable solid
particle with a spherical shape that has been recently
tested in Japan [52]. The particle size is precisely
calibrated in 50-um increments ranging from 53 to
350 um and initial experience suggests that emboli-
zation with use of these particles leads to extensive
tumor necrosis of large nodular HCC, sparing use of
chemotherapeutic agents [52].
E. Liapi and J.-F. H. Geschwind
a Stable solution of Doxorubicin-elm^ng lie ads iPKHumON He.Ldsi m ;.„.iiie. Note thiit red-jolored doxorubicin
e the bead, b Confer I last-:' nii^i'ostOj.iy i::..-,^. ?::.:iwiijg d> 'Xo: Lilian di-n it-;:: !■:■:'. in (he bend. Progressive
sei/ii'.'iiiiig slji.'ws iiKi: ".lit; ■r::-^. :s co:'.iViiL[\i:ed iii the o..".e: [•■'.■r.ioi's of riie be;id. i C ■.■'..: r.esy ci A:'dy Lewis. R i i. .j ■. > j j ] y ;■ . i lt ^ e s .
UK, Ltd, Surrey, UK]
17.3.5.2
Drug-Loaded Embolic Agents
The concept of drug-loaded microspheres for che-
moembolization is not new, and several attempts
have been made over the past decade to design
microspheres loaded with chemotherapeutic agents
suitable for intraarterial delivery. Cisplatin-loaded
poly(d,l-lactide) microspheres for chemoemboliza-
tion [66], doxorubicin incorporated into albumin
microspheres [26], poly (benzyl l-glutamate) (PBLG)
microspheres containing cisplatin [34], 5-fluoro-
uracil-loaded chitosan microspheres [16] are some
examples of initial attempts to create vehicles of che-
motherapeutic agents for precise tumor targeting.
Today, the development of nanotechnology com-
bined with the robust research activity in tumor
pathophysiology has boosted up the production of
noveldrug carriers for systematic or local tumor tar-
geting. A promising example of this new category of
embolic materials is the doxorubicin-eluting beads,
which will be further analyzed.
17. 3. 5.2. J
Polyvinyl Alcohol Hydrogel Drug-EIuting Beads
PVA hydrogels are non-biodegradable and relatively
biocompatible and can be easily fabricated since they
possess high stability under a range of temperature
and pH conditions [43]. Their structural mechanical
properties are similar to those of human soft tissues
and provoke a limited inflammatory response [54].
Because of the amphophilic nature and microporous
architecture of hydrogels, drugs can be incorporated
in hydrogel coatings and can be typically released
within hours to weeks [54]. The release of the loaded
drugs in acidic environment represents another
important property of these polymers.
Recent development of a new PVA hydrogel bead
has enabled accurate doxorubicin loadings to be
achieved, with subsequent slow first order release.
This novel drug-delivery system has been recently
evaluated for intraarterial treatment of hepatic
lesions [22]. Doxorubicin-eluting beads (DC Bead
for loading by the physician and PRECISION Bead
preloaded with doxorubicin, Biocompatibles UK
Ltd, Surrey, UK), are designed for intraarterial infu-
sion and selective tumor targeting [14].
The significant advance of these beads is the dem-
onstration of an effective process for consistent drug
release that controls local tissue response. Recent
animal studies on a model of liver cancer have con-
firmed the in vivo slow release of doxorubicin over-
time within the tumor, with maintenance of a high
concentration of drug for up to 14 days. Pharmacoki-
netic data of this study showed near complete absence
of doxorubicin within plasma, while intratumoral
doxorubicin concentrations remained high [22].
Clinical studies that are necessary to support this
initial report of efficacy are currently in progress in
Europe and Hong Kong. These beads are not cur-
rently available in the US market. Irinotecan-elut-
ing beads for metastatic colon cancer are also under
development.
iieSe;l:ch .illu lr 11 T LI : c I"' if.
:t Oncology Embolorlieiapy
D mo rub I tin Ptiarmaco kinetics
Fig. !7.'"'. 1- 1 i.ii in -.!■."■ 'ki nc lie sluciy results of cioxoi ubicin-eliiiiiig beads I ! : zBl 1:1 i; VX-J i-.ibbi: model of liver Initio: show lug:'
g concentration wiih mini in ill systemic toxicity. Noie riie sigiiilicinUy lugije: levels of doxorubicin found ir
or, peaking 3 o.iys -.me: ueaiineivi. ^usljined levels of ioxoi'ubici:'. iiie-.isnied in the tumor 14days i
A future approach on this category of embolic
agents would include a sophisticated regimen of
timed release drugs appropriate to the pathologic
stage of cancer, followed by a treatment that sup-
presses angiogenesis (such as bevacizumab) or dis-
rupts a neoplastic metabolic pathway (like 3-BrPa).
Advancements in Embolization Technique
Several variations in the techniques of embolo-
therapy have been reported. Some of the common
steps of the procedure include the patient's over-
night fasting and volume loading, administration
of conscious sedation and a visceral angiogram
to identify the arterial anatomy of the liver, the
size and locations of the tumors, and their feed-
ing vessels and portal venous potency. A catheter
is advanced beyond the gastroduodenal artery (to
avoid extrahepatic embolization), and depending
on tumor location and institution's protocol to
lobar, segmental, or subsegmental branches feed-
ing the target lesion(s).
A common objective of every interventional
oncologist is to preserve as much functional liver
tissue as possible. Currently, there is no consensus
on how selective (lobar vs. segmental) chemoem-
bolization should be. Many centers prefer to focus
on one lobe of the liver at each treatment session,
regardless of the extent or number of tumors, so as
to avoid a prolonged postembolization syndrome or
postinterventional liver failure. Others may choose
an even more selective approach, by engaging a seg-
mental or subsegmental feeding artery. Longer sur-
vival seems to be related to multiple TACE sessions,
which require, however, long-term maintenance of
arterial patency. Further research though is required
to assess the effectiveness of long-term arterial
patency [25]. Controversy also exists over the best
treatment scheme for repetitive treatments and over
the timing for repetition of the treatment session.
Some centers prefer to treat patients at fixed timing,
whereas others upon disease progression after the
initial response. In our institution, the decision to
re-treat is made on the basis of imaging and clini-
cal assessment of tumor response. Appointments for
imaging and clinical evaluation though are sched-
uled within a fixed interval of time after treatment.
In the future, a better knowledge of genetics and
causes of hepatic malignancies may result insignifi-
cant modifications of hepatic artery embolization
techniques.
17.5
Conclusion
Several questions remain unanswered, such as which
is the best embolization agent, which is the best
chemotherapeutic drug, or how can we increase the
intratumoral concentration of the drug. The lack of
large prospective randomized trials and the current
difficulty in conducting meta-analyses on hepatic
oncology embolotherapy, along with the absence of
effective systemic therapy for unresectable primary
and metastatic liver disease, urge intense efforts and
the continuation of research on oncology embo-
lotherapy. New developments in drug regimens,
embolization materials and new variations in the
embolization technique are rapidly changing the
image of oncology embolotherapy and hopefully,
1J.-F.H. Geschwind
will positively influence the outcome oft:
and patient survival.
The interventional radiologist should also bear
in mind that successful embolotherapy depends on
factors beyond the embolic agent selection, or the
choice chemotherapeutic cocktail. Technical skills,
experience, familiarity with the underlying patho-
logic processes, and appreciation of the importance
for constructive collaboration with other special-
ties, are also essential for every successful oncology
embolotherapy treatment.
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External Carotid
18 Technical and Anatomical Considerations
of the External Carotid System
Paula Klurfan and Seon Kyu Lee
EGA Anatomy 235
r: in h' vol; eiirnJ 1'eivlopmeni 2 35
External Carotid System 237
Technical Aspects or' Hrad and Neck
E in 1x0 iz.;t ion 240
Therapeutic Techniques and Materials 241
Iviedicaiion 245
References 245
The external carotid system (ECS) is a key arterial
supply for the craniofacial and neck regions. Even
though the internal carotid artery, the thyrocervi-
cal, costocervical, and vertebral arteries are also
supplying these territories, this chapter will focus
on the anatomical aspects of the ECS and the tech-
nical implications of the endovascular management
of these regions.
18.1
ECA Anatomy
The external carotid artery (ECA) is in general the
smaller branch of the two terminal arteries of the
common carotid artery. The site of the carotid bifur-
cation is variable; however, between the C4-C5 and
the C3-C4 is the most common levels. Despite its
great anatomical variability, this artery is classically
described as having eight main branches. The main
P. Klumjam, MD
lnterveiiiioiii.il Neuroradiology Conical relkuv. Department
of Medical Imaging, University o'i Toronto. Toro:i;o Western
Hospital, University Health Network, Suite 3MC-429, #399
Bathurst Street, Toronto, Ontario, M5T 2S8, Canada
S. K. Lee, MD, PhD
it Professor, Staff Interventional anc. Diagnosis Neil re-
gion of Neuroradiology, PeparTiiient of Medi-
cal l:r: aging. University o: Toro:r:o, Toronto Western Hospital,
University Health Network, Suite 3MC-429, #399 Bathurst
Street, Toronto, Ontario, M5T 2S8, Canada
trunk of the ECA de<
branches to the tongue, deep face, and neck. The
arterial termination is located at the level of the
parotid gland, where it is divided into the super-
ficial temporal artery and the internal maxillary
artery. Initially the ECA lies anterior and medial
to the internal carotid artery (ICA), then it courses
posterolateral^/ as it ascends in the carotid sheath in
front of the internal jugular vein. During its cervical
course it is covered by the sternomastoid muscle and
crossed by the hypoglossal nerve, lying anterolater-
al^ to the vagus nerve.
18.2
Embryological Development
The wide variety in the anatomical disposition of the
arterial tree of the head and the neck is explained
by the embryological development of the vessels in
these anatomical areas. The specific supply to every
territory is related to a general hemodynamic bal-
ance in the whole region. This relationship is estab-
lished between the territory and several potential
nutrient vessels.
During ontogenesis, the arterial supply to every
territory will be the result of this hemodynamic
balance, achieved by anastomosis, annexation, and
involution of blood vessels.
Initially, at early embryonic stages, the ventral
and dorsal aortas communicate by a certain number
of arterial bridges, the aortic arches (1 to 4 in the
craniocaudal direction). Other embryonic arter-
ies are the primitive maxillary artery, dorsal oph-
thalmic artery, ventral ophthalmic artery, anterior
cerebral artery and the longitudinal neural arteries
(Fig. 18.1).
During the subsequent stages, some of these
arteries undergo modifications through regres-
sion in the regions of the ventral ophthalmic artery,
dorsal aorta and the ventral portion of the first two
aortic arches.
P. K.urf.tn .tad L=. K.Lee
Fig. 18.1. EGA embrvontc develi.piuenl at early stage. J, pro-
atlantai artery; J, hypc-glo^a! artery; .!. third aortic arch; 4,
second aortic arch; 5, first aortic arch
The dorsal aorta will give rise to the third aortic
arch which, subsequently, will reach the remnant of
the ventral pharyngeal artery, becoming the exter-
nal carotid artery. As the proximal dorsal aorta
involutes, the ventral aorta becomes the definitive
common carotid artery dividing into a primitive
internal carotid artery and external carotid artery
(Fig. 18.2).
The original ventral pharyngeal artery turns
into the facio-lingual system, while the hyoid artery
and the stapedial artery will evolve to become the
internal maxillary artery and the middle meningeal
artery (Figs. 18.3, 18.4)
The caroticotympanic artery originates from the
proximal segment of the hyostapedial trunk, while
the inferolateral trunk (ILT) is a remnant of the dorsal
ophthalmic artery. The definitive ophthalmic artery
originates from the primitive ophthalmic artery.
Some implications of this vascular development
rely on the fact that every vascular segment lies
between the origin of two embryonic vessels, and
therefore they may be the point of entry of vascular
rerouting in cases of segmental agenesis of part of
the ICA proximal to the embryonic vessel: rerout-
ing via the hyoid artery through the ascending
pharyngeal artery at a cervical ICA agenesis, otic
or trigeminal artery in a cervical or petrous agen-
esis or even primitive maxillary artery originating
from the carotid siphon on the contralateral side. In
combined cervical, petrous and cavernous agenesis,
rerouting through a complex cavernous network
belonging to the internal maxillary artery has been
described.
Anatomic variants result from errors inthe mul-
tiple steps during the development of the;
The hemodynamic balance of the intern
maxillary and external carotid arteries ca
very different anatomic variants.
Two types of craniofacial branches aris
external carotid artery:
• The arteries that supply the muscular and teg-
mental structures, arising on the whole from the
external carotid artery.
• The arteries that supply the peripheral cranio-
encephalic system (cranial nerves), which evolve
from internal carotid to external carotid arteries,
like the maxillary system that arises originally
from the stapedial artery.
al carotid,
e from the
Fig. 18.3. Final appearance of the external carotid artery. 1,
occipital artery; 2, ascending pharvageal artery; 3. inferior
tympanic: artery; 4, internal carotid artery; 5, lingual artery;
6, facial artery; 7, posterior auricular artery: S, superficial tem-
poral artery; 9, petrous branch; 10, middle meningeal artery;
! !, maxillary arterv: ;_', Iransverse facial artery
Fig.18.2. EGA embryonic development at a later stage. I,
occipital artery; 2, a scea da nt phaivagea! arterv: 3. fa cio I in glial
artery; 4, maxiKoataadihr.lar arterv; 3, supraorbital artery; 6,
internal carotid artery
■t" :he !£xrei j : ,i I '.I.inxid Svst
Fig. 18.4. Angiographic view of the rxiernal carotid artery. I,
fadolingual trunk; 2, c>ll ipital aneiv; .!, miernul maxillary
artery; 4, superficial temporal anery; :■, middle meningeal
involved i
: of the craniofacial supply is the one
i the vascularization of the central ner-
II, and arises on t lie whole from the ICA.
the lacrimal variant, the orbital supply is limited to
an anastomosis across the superior orbital fissure,
while in the meningolacrimal variant; the middle
meningeal artery is responsible for the supply of a
portion of the intraorbital territory.
Other branches of the maxillary artery to the
orbit include the anterior deep temporal, the infra-
orbital and the sphenopalatine arteries. These arter-
ies correspond to remnants of vessels arising form
the infraorbital artery of the vertebrates, witch gives
rise to the orbital artery.
There are multiple anastomoses between the
intraorbital branches with the external carotid
system only supplying the periorbital region. This
includes the internal maxillary, superficial tempo-
ral arteries and the facial system.
Supply to the cavernous sinus region may arise
from the ECA. Arterial branches arise from the
different segments of the cavernous carotid artery
and course medially, laterally and in the direction
of the posterior cranial fossa. These branches will
anastomose with branches of the external carotid
artery, which will allow a functional approach to
this region. The ILT always anastomoses with the
artery of the foramen rotundum, the middle menin-
geal artery and the accessory meningeal artery. It is
also called the inferolateral trunk of the c
18.3
External Carotid System
■ ECA
It is important to undei
branches are in a hem
internal maxillary systen
of branches, whether theii
extracranial.
The ophthalmic artery ;
supraorbital branch of the stapedial artery win
later becomes the middle meningeal artery. In addi-
tion, I he orbital artery will also anastomose with the
primitive (and later definitive) ophthalmic artery,
from the supracavernous internal carotid artery.
Because of the different variants in the involution
of the proximal segment of the orbital or ophthal-
mic arteries, the supply to the orbit will finally arise
exclusively from the ICA, the stapedi
or both.
The embryologic hemodynamics i
to predict the arterial variants that i
itand tha
idynamic balance. The
consists of two groups
course is intracranial or
s originally from the
system (ECA)
lakes itpossible
an be observed
n the orbital region. The role of the middle menin-
geal artery in supplying the orbit can be seen to vary
from one individual to another and from one side
to the other in the same individual (Fig. 18.5a,b). In
The significance of these various arrangements
lies in the fact that the anastomoses at the cavernous
segment of the internal carotid artery constitutes
the most common pathway of reestablishing blood
supply in acquired occlusions of the internal carotid
artery. The acquired constraint re-orients the hemo-
dynamic balance in order to support and preserve
the territory distal to the acquired occlusion.
Embryologically, the dorsal ophthalmic artery,
the stapedial artery, the trigeminal artery and the
primitive maxillary artery are involved in this anas-
tomosis.
The primitive maxillary artery originates from
the medial surface of the C5 portion of the carotid
siphon. It supplies the posterior hypophysis where
it anastomoses with its counterpart on the other
side. It may arise from a common trunk with the tri-
geminal artery and their common remnant is then
a single artery that arises from C5 and gives off all
the meningeal, hypophyseal and
of this region. This variant seems t
The primitive maxillary artery ah
meningeal branch for the dorsum s
artery of the clivus). This
al branches
3 be rather rare.
) gives rise to a
:llae (the medial
lastomoses with
iunterpart on the contralateral side and inferi-
P. K.LirL-ii .-:'J J. K. L?t
Fig. 18.5 a-c. Anatomical variation. Orbit suppl;
ningeal artery (arrow) a. On
of left EGA angiography, choroid a I blush is clearly shown
[arrow) b. Intern.il carotid artery angiography demonstrates
;urysm,but no ophthalmic artery
lalized from the ICA c
orly with the clival branch of the hypoglossal branch
of the ascending pharyngeal artery. The persistence
or unusual origin of the primitive maxillary artery
may be demonstrated in certain variants. For exam-
ple, when there is a cervical internal carotid artery
agenesis, the internal carotid artery may arise from
the contralateral internal carotid artery through a
trans-sellar anastomosis of the persistence primitive
maxillary artery system. The contralateral intracav-
ernous origin of the internal carotid artery can be
developed through the embryological remnants of
the primitive max il larva ileiy that include posterior-
inferior hypophyseal artery (anterior to the clivus}
and medial clival artery (posterior to the clivus).
Other ICA branches arising from the C5 segments
are the posteroinferior hypophyseal artery, the lat-
eral artery of the clivus and the recurrent artery of
the foramen lacerum. These are constant vessels that
are anastomosed with the external carotid system
through the ascending pharyngeal artery and in
some cases with middle meningeal artery branches.
The ECA is mainly responsible for supplying the
supratentorial dura which covers the convexity. The
anterior ethmoidal artery or the frontal branch of
the middle meningeal artery supplies anterior aspect
of dura mater. These arteries are the main suppliers
for the anterior parietal regional dura of the con-
vexity, but the blood supply may also come from the
Technical and A
is of the External Carotid Svst
ophthalmic or intraorbital lacrimal artery which
reaches its territory passing through the superior
orbital fissure. The parieto-occipital trunk of the
middle meningeal artery supplies the meninges of
this region and the petrosquamosal trunk courses
in the groove of the petrous and squamous portions
of the temporal bone. These vessels are branches of
the middle meningeal artery reaching the midline
where they participate in the supply to the superior
sagittal sinus and give descending branches to the
fa lx cerebri.
Anastomoses to the cortical pial (cerebral) arter-
ies from these dural arteries are rare and are mainly
found in occlusive diseases of the ICA.
The extracranial branches of the maxillary
artery include arteries that supply the nasal cavity,
the choana and the nasal part of the pharynx and
its walls. The blood supply of this region is particu-
larly rich and presents multiple anastomoses to vital
structures.
The accessory meningeal artery is the main
branch of the extracranial middle meningeal artery
and anastomoses with the mandibular artery rem-
nant of the ICA and the superior pharyngeal branch
of the ascending pharyngeal artery. The accessory
meningeal artery anastomoses with the Eustachian
tube meatus arterial branch of the ascending pha-
ryngeal artery and the ptervgovagntal arteryinfero-
medially, and with the descending and/or ascending
palatine arteries interiorly. This variety of territories
supplied by the accessory meningeal artery makes
it potentially responsible for the arterial supply for
numerous lesions arising in this region.
The pterygovaginal and vidian arteries are also
supplying these territories with multiple anastomo-
ses. The pterygovaginal artery anastomoses with the
accessory meningeal, ascending pharyngeal and the
mandibular branch of the ICA when it is present.
The vidian artery is rarely visible during the maxil-
lary artery angiography, probably due to the bone
density through which it courses. The vidian artery
may anastomose with a corresponding branch of the
petrous segment of the internal carotid artery.
The sphenopalatine artery, the terminal branch of
the internal maxillary artery enters the nasal cavity
where it is divided into a septal, medial branch and
a lateral branch that supplies the conchae. These two
arteries have a distinctive appearance on the angio-
graphic views. These branches usually anastomose
with the anterior and posterior ethmoidal arteries,
which arise from the ophthalmic artery system, at
the anterior and posterior ethmoidal cells, and even-
tually connects the external and internal carotid
systems. Other anastomoses are the septal branch
of the superior labial artery (medially} and later-
ally with the alar arteries, also branches of the facial
artery. There is also a septal anastomosis of the ante-
rior branch of the greater palatine artery with the
posterior ethmoidal artery and the olfactory artery
(a branch of the anterior cerebral artery).
The upper arch of the mouth and the mandibii-
lozygomatic area branches supply the maxilloman-
dibular region. This system provides connections
between superficial (cutaneous) and deep structures
(bone and mucosa).
The pharyngo-occipital system consist of an
occipital artery, witch supplies the cutaneomuscu-
lar elements and an ascending pharyngeal artery
that is responsible for the meningeal and neural
territory. The latter vessel is a metameric artery
that has numerous anastomoses with the ICA and
its branches are in hemodynamic balance with the
suboccipitocervical system.
The caroticovertebral anastomoses can be found
as the persistence of the embryonic segmental ves-
sels in adult. The type II proatlantal artery corre-
sponds to the second segmental artery. It arises from
the future external carotid artery and courses poste-
riorly to the second cervical vertebral canal, where it
supplies C2. This embryonic artery regresses to give
the C2 occipito-vertebral anastomosis. However,
when it persists, it runs into the cervical canal from
C2 to CI and penetrates the dura at the CI level, sim-
ilar to the conventional vertebral artery. Additional
variants can be seen, including the occipital artery
origin of PICA at C2 that is corresponding to an
equivalent of the radiculopial artery for the cord.
Most often, the occipital artery arises from the
external carotid artery, in some cases as a common
trunk with the ascend ingpliarv ngea la itery. In other
cases they may arise from the origin of the internal
carotid artery. The occipital artery may also arise
from the vertebral system via the branch of the first
or the second vertebral body level or, more rarely,
from the cervical arteries or from the vertebral
artery at C3 level.
The ascending pharyngeal artery arises posteri-
orly from the inferior part of the external carotid
artery. It may also arise from the occipital artery or
from the origin of the internal carotid artery. More
rarely both ascending pharyngeal artery and occipi-
tal artery may arise from the ascending cervical
artery. Three pharyngeal branches of the ascending
pharyngeal aiterv are usually seen including infe-
rior, middle and superior branches. They supply the
of the naso- and
P. K.LirL-ii .-:'J L=. K. Lee
oropharynx. They anastomose on the midline with
their counterparts and with the adjacent pharyngeal
branches on the same side. The superior pharyn-
geal (or Eustachian) branch reaches the Eustachian
tube's meatus on its medial side, lateral to the pha-
ryngeal recess. It anastomoses with the correspond-
ing branches of the accessory meningeal and ptery-
govaginal arteries as well as forming a more medial
and superior anastomosis with the mandibular ves-
tige of the first aortic arch from the petrous segment
of the internal carotid artery.
From the superior pharyngeal branch, the carotid
branch arises to the carotid canal. This carotid
branch ascends through the foramen lacerum and
accompanies the internal carotid artery up to the
cavernous sinus, where it anastomoses with the
inferolateral trunk and with the recurrent artery of
the foramen lacerum, arising from the C5 portion
of the carotid siphon, which supplies the internal
carotid artery wall and sympathetic nerve fibers.
The inferior tympanic branch lias certain distinc-
tive features. This artery accompanies the tympanic
branch of the 9th cranial nerve in the inferior part
of the tympanic cavity, where it usually divides into
three branches. The ascending branch anastomoses
with the petrosal branch of the middle meningeal
artery, accompanying the major deep petrosal nerve.
An anterior branch joins the caroticotympanic
artery, following the neural anastomosis between
the tympanic branch to the ninth cranial nerve
and the pericarotid nervous plexus. The posterior
branch that courses towards the facial canal, where
it anastomoses with the stylomastoid artery.
The neuromeningeal branch gives rise to hypo-
glossal and jugular branches. It enters the hypoglos-
sal canal and supplies the 12th cranial nerve and the
meanings of the posterior cranial fossa, where it is
in balance with the other arteries of this region. This
artery gives off medially a descending branch which
s with the vertebral artery at the third
1 space. The jugular branch, which arises
from the same neuromeningeal trunk as the hypo-
glossal branch, enters the cranial cavity through the
jugular foramen, where it supplies the ninth, tenth,
and eleventh cranial nerves.
In order to be able to perform endovascvilar
embolization procedures in the external carotid
artery it is important to understand the physiologi-
cal characteristics of the blood flow of this particu-
The normal hemodynamic characteristics of the
ECA are the absence of diastolic forward flow. This
represents an important risk during embolization
procedure due the possibility of material reflux.
Thus, it is highly recommended to perform the
embolization procedure during the systolic phase
with a small volume on each injection of embolic
materials.
Autoregulation mechanisms have been described
to be more effective in the internal maxillary artery
and the pharyngo-occipital system, whereas the
facial artery has not shown to respond as effectively.
Vasoconstriction as a response for hypertension or
mechanical trauma is observed in large or medium
sized arteries whereas small distal arteries seem to
react with true regulatory mechanisms.
18.4
Technical Aspects of Head and Neck
Embolization
Preoperative medication is usually not needed, aside
for anesthesia drugs or those used for other medical
conditions. A urinary catheter is recommended for
an accurate measurement of fluids output and will
prevent any discomfort for the patient in prolonged
procedures.
General anesthesia is necessary in most of the
endovascular procedures for head and neck condi-
tions, particularly in the pediatric population, in
ethanol injections {paint til procedures) and patients
with lesions located near the airway where swelling
may obstruct the airway.
Where the lesions are located at or near the a ir.vay,
and combined procedures are schedule (surgery) a
prophylactic tracheostomy may be considered.
Neuroleptic analgesia is a useful tool for diag-
nostic angiography, when neurological monitoring
throughout the procedure is necessary and when
general anesthesia is contraindicated in the older or
medically compromised patients. Usually a combi-
nation of an analgesic (opiate derivates) with seda-
tive drugs (benzodiazepines) is useful to allow the
patient to tolerate the procedure.
Conventional Seldinger technique is generally
used for the majority or the procedures, and a femo-
ral sheath with hemostatic valve (4 to 9 French) is
placed into the femoral artery to allow the exchange
of the catheters, reducing the trauma to the artery.
Diagnostic procedures are performed with 4 to 5
French diagnostic catheters: single (Berenstein) or
double curve (Sidewinder) depending on the tortu-
osity of the vessels. These catheters are used in com-
bination with guidewires (0.035") (Fig. 18.6).
is of the External Carotid Svstem
Fig. 18.6. Diagnostic citlrieleis vcil; si in:'' lei Rerenstein), double
curve i Sidewinder: jiii;". guide wire with curved tip
Therapeutic Techniques and Materials
A great variety of microcatheters,
embolic agents and drugs are available for the man-
agement of a number of indications and purposes.
The success in the endovascular technique and the
achievement of the treatment goals not only depend
on the technical skills of the operator but also in the
appropriate selection of the endovascular material,
based on the knowledge and the experience of the
interventional neuroradiologist.
Microcatheters are manufactured in different
sizes: 0.018", 0.014", 0.010" systems allow to navigate
the arterial branches with different flexibility. These
microcatheters are used in combination with 0.018"
to 0.010" outer diameter microwires that gives the
required support to the system as well as a torque
control to direct the tip of the catheter. Most of these
catheters are performed with polyethylene and allow
shaping the catheter tip. This is usually performed by
exposing the end of the microcatheter to the steam
source. Some of these microcatheters are available
with a pre-shape d tip with different angles.
Flow guided microcatheters are a second type of
microcatheters designed to navigate with the blood
flow with a much smaller outer diameter (0.012"
- 0.018") achieving a more distal selective catheter-
ization. The development of these microcatheters
has permitted interventional neuroradiologist to
treat a more extensive variety of craniofacial and
neck lesions that were beyond the reach of the endo-
vascular techniques with the previous generation of
microcatheters.
Balloon catheters are divided into two main
groups: those used for blood flow control and test
occlusion, and those used as the embolic agent
themselves, detachable balloons.
Single lumen balloon catheters (Hyperform,
Hyperglide) are available in 4-7 mm in diameter
and 10 to 30 mm in length. To inflate this balloon, a
microwire should pass the balloon and stay beyond
the microcatheter. A 50% iodine contrast material is
used for the balloon inflation.
Serbinenko first designed and introduced the
detachable balloon for the clinical usage in 1974.
With the evolving designs and materials, they have
been a good embolic device for single high flow fis-
tulas of major arteries in the trauma or congenital
types. These are made of latex or Silicone with an
Inflation diameter of 4 to 35 mm and are provided
with a radiopaque marker which permits the bal-
loon location under fluoroscopy before the inflation
of the balloon. Detachable balloons can be hand
assembled and be used with high reliability for clos-
ing the selected vessel at a precise location. They can
be removed and changed if the position or size of the
balloon is incorrect (Fig. 18.7a-e) before its detach-
ment. Once the desired position is reached, gentle
and continuous traction is applied on the delivery
catheter until the detachment occurs.
The selection of the embolic agents is determined
by the goal of the procedure, vascular territory and
type of lesion. Classically they are divided into solid
or liquid agents.
Among the solid agents, particles are precut
agents used for mechanical blockage of a selected
territory. Several materials and sizes are available
depending on the result required.
Absorbable particles consist mainly is Gelfoam
(gelatine sponge) powder (40-60 um) or particles
(any size), the use of autologous clot or Avitene has
also been described. The occlusion achieved with
this material is not permanent and vascularization
is reconstituted in 7 to 21 days after the procedure.
The Gelfoam can be easily cut, and placed in con-
trast material to be injected through small lumen
catheters.
Gelfoam powder can be used for tumor preop-
erative embolization, in highly vascularized lesion.
This material is used also tor endovascular manage-
ment of the epistaxis due to the fact that the embolic
occlusion occurs at the capillary or precapillary
level. The Gelfoam is mixed with contrast material
and is injected under fluoroscopic monitoring with
a 1-3 cc Luer-lock syringe held in horizontal posi-
This embolic agent should be used carefully with
a good positioning of the catheter and continuous
V. [viiri'.in .nid L=. K.Lee
Fig. I8.rn -e. Louisas: en: - , a need CT scans a, b in I J-ycLir-old boy with slovdv enlarging rnlsaiile mass legion involving [lie ^:"l
check region cenionsli-.Uc prom men; vase nl Lit channels lei": pica uric:; l-.ir a ten : iirrpirs). Let': I Liters I cxlc: na! en rod d angiogram
in early c and Lite arterial phase d demons tilled sing.c hole ti = : u J li li s comniunicadon •:'<iitl?ii , >] between proxan.d interna!
maxiLai v a • ic: y L ! .::d adiactii; facia, vein. T:aii5aj \t: iai .ateriLi. single b.i !..:■■ .n detLiclinic::: w.is per: oi med at the fistulous 51 :e
rescuing in iiiinitdi-.iic complete oblilei j\:- 'i: of ilie f:s:uL: and several coils were deposited :n trie proximal ex:ern.;i carotid
artery for added protection. Po5;-c:i;boliza:io:i lef: lateral coin men carotid angiogram e demonstrated clo5iire oi" die AVF. No:e
the c.151 of die 5 ingle bnlloon iiinoiisi and ilie discivpancv be: wee:: the grossly enl.-:gec proximal Ir.;nk 01" the external carol id
artery versus the size of die inlei nal carotid artery
fluoroscopic monitoring due to multiple anasto-
mosis between the external carotid system and the
intracerebral circulation ,i<; well as the cranial nerves
arterial supply from the ECA branches.
Gelfoam pellets are mainly used for preoperative
hemostasis, however, they do not reach the tumoral
capillary bed, and therefore no necrosis is observed
in the treated territory.
When you cannot reach to the target vessel (so
called superselectivity) but a permanent agent must
be used, a Gelfoam particle 1x2 or 1x3 mm or even
larger sized particles can be used to occlude the
proximal part of a normal vessel. This method will
protect a normal vessel by preserving its distal part
and should be able to change the hemodynamics of
the involved territory so that embolic agents would
only reach the pathological vessels. Later on, the
absorption of the Gelfoam particle should restore
the normal flow into these arteries. In some other
cases, Gelfoam can be safely used as an occlusive
agent. The^e include trail malic arterial hemor rhet-
or traumatic aneurysms.
Among the nonabsorbable embolic materials,
Polyvinyl Alcohol particle (PVA) is one of the most
widely used. This consists of a water-soluble, bio-
compatible material made by a reaction of polyvi-
nyl alcohol foam with formaldehyde. When it is
moisturized, it expands its volume up to 20% more
Ttvhllk";'.! ond
.i.m] Coa^deri'.tions of :hr cxijjtuiI ■! ^ : ■: "_ [■,! ?vsi
Chan its dry volume. PVA suspensions are available
as dried particles measuring 140-250 to 590-1000
microns in size. These particles are mixed with con-
trast material. PVA has a high coefficient of friction
and its injection may be difficult. For this reason,
it is recommended to continuously mix the suspen-
sion in between the material injection and to inter-
mittent flush the system to prevent PVA deposits on
the catheter hub.
The PVA has been described to have an embolic
effect not only by occluding distal small to medium
size vessels but also by slowing the flow in the
treated vessel producing stagnation and, therefore
clot formation. Even though this material is known
to be non-reabsorbable, recanalization occurs,
mainly because of clot reabsorption and re-endo-
thelialization of the PVA deposits on the vessel
walls. PVA is a useful embolic material for preoper-
ative devascularization for tumors, some vascular
malformations such as dural arteriovenous fistulas
or flow rerouting in preparation for IBCA or etha-
nol injections. A catheter that was previously used
for particle embolization should never be used for
an angiogram of intracerebral arteries (ICA or Ver-
tebral artery).
NBCA (N-Butyl-2-Cyanoaciylate) is a vinyl
monomer of the alkyl-2-cyanoacrikites. This mate-
rial is the most widely used liquid embolic agent and
is characterized by being non-reabsorbable, produc-
ing almost immediate solidification when it reaches
a polarized fluid such as saline and blood. Polymer-
ization of the NBCA occurs when it combines with
an ionic solution such as contrast material, saline,
blood or endothelium producing an exothermal
reaction in a few seconds. Polymer retardants are
generally used to achieve the ideal setting time for a
particular injection. Iodized Ethyl Esters (Lipiodol)
are usually a good combination as a polymer retar-
dant for the NBCA. It has been shown to maintain
a good dilution retarding polymerization in 4 to
8 seconds for every 0.2 to 0.5 cc in 1 cc of NBCA. The
viscosity of this material may be a concern but usu-
ally it can be injected in the smallest catheters used
in interventional procedures.
Due to the radio-opacity of the Iodized Ethyl
Esters, it can be used with NBCA without the use
of an opacifying agent unless the NBCA concen-
tration is over 50% of the mixture. In those cases
Tantalum powder is recommended using 1 gram
for every 1 cc of NBCA. Before the injection of the
NBCA mixture, a 5% dextrose solution should be
used to rinse the catheter. This will prevent the
NBCA to solidify before reaching the targeting tis-
sues. Injection of NBCA must be done under con-
tinuous fluoroscopic control after the superselec-
tive placement of the microcatheter. Depending on
the therapeutic goal, NBCA/retardant mixture will
be prepared to achieve venous/capillary penetra-
tion or arterial occlusion (endovascular ligation)
(Fig. 18.8a-d). When a high flow vessel of fistula
is to be treated, combined technique may be used
with using liquid coils.
Ethyl Alcohol (95% Ethanol) is an effective and
aggressive liquid embolic neent. Its does not produce
a mechanical occlusion of the vessels but produces
an immediate tissue reaction due to the cytotoxic-
ity on the blood and endothelium. The use of Ethyl
Alcohol results in a systemic distribution but the use
of up to 60 cc of alcohol in an adult is below the toxic
blood concentration. Ethanol is an effective embolic
material to induce necrosis and endothelial damage
but may not be indicated for high flow conditions or
when a mechanical occlusion is expected. The con-
trol of the Ethanol during its injection is very poor
especially its distribution in the vascular territory.
Therefore, its use is generally limited to venous mal-
formation and some limited territories of the ECA.
In some cases it can be combined with the use of
PVA particles or Gelfoam. Ethanol procedures must
be performed under general anesthesia as it causes
severe pain during the injections. In addition, spe-
cial attention should be taken regarding the venous
outflow of the malformation witch may involve the
ophthalmic vein, cavernous sinus or the vertebral
epidural plexus. After the ethanol injection the area
indurates and swells, starting a few minutes after
the infusion and lasting 3-7 days. Final result may
be expected after 1 to 5 weeks. Local skin necrosis
may be seen after but usually is limited and heals
spontaneously.
Other materials have an important role in the
end ova s cu lar management of the ECA. Detachable or
pushable coils represent a safe option when arterial
occlusion is required: arterial ligation, hemorrhagic
emergencies (carotid blowout), blood flow rerouting
techniques or combined endovascular embolization
with other embolic agents. Several types of coils are
widely available. Detachable bare platinum coils
(Fig. 18.9) allow very precise coil deployment, and
can be removed if the size is incorrect or coil place-
ment. Pushable coils are directly deployed into the
vessel while fibered coils have filaments that induce
stagnation and local thrombosis. The 2nd generation
of coils have been designed with combined material
that may induce inflammatory reaction in the sur-
rounding vascular tissue (GDC Matrix® coils) or a
P. K.LirL-ii .-:-J L=. K.Lee
Fig. 18.8a-d. Selective occipital :;:'gLOg[aiii in lateriu view a ^emonsmues lugj'.-row scalp AVM which, was also supp.ieJ ov
bi -.inches 01" ".he ipsilitte; j I ;;nd cont:aljtei-.il stipe; f-.chi! tempc-ial ,11 lenes .-[id com ia lateral occipi:al artery : 110 r slioii-ti). Follow-
ing tiansa; .^: iai p.ntiiu embi'lizstjon wit:: glue iuid parties 0:' PVA into ti'.ese vessels a yeictit.mtotis approach wjs jerfoi me J
b,cwith iiijeclioj) of glue (S09d NRCA/ 50% Lipiodol) resulting in complete obliteration of the AVM nidus as shown on the post
embolization left externa! carotid angiogram d
Fig. 185. Detachable coils are available in si
3D coils may be used for vascular occlusio
Technical and A
is of the External Carotid Svst
hydrophilic component that allow the coil to expand
4 to 20 times its volume to achieve a better vascular
occlusion (Hydrocoils®).
The selection of the embolic material will vary
depending on the vascular territory, the vascular or
tumoral lesion, the therapeutic goal and the previ-
ous experience of the interventional neuroradiolo-
gist.
18.6
Medication
Heparinization is usually recommended when coax-
ial catheter assembly systems are used to prevent
fibrin clot formation. Initial prothrombin time,
partial thromboplastin time and activation coagu-
lation time is recommended to use as a baseline to
calculate the dose of the protamine sulfate dosage
when heparinization is to be reversed. Complete
heparinization of the patient can be achieved with
a bolus dose (50 IU/Kg) and a maintenance infusion
(500UI/Kg in 24 hours) that is initiated once the
arterial access is obtained.
Flushing solutions are prepared with heparin
using 2000 IU/ 1000 ml of 2.5 D/W in children and
4000 UI/ 1000 ml of 2.5 D/W.
Corticosteroids are not generally used during the
endovascular management of the ECS. Its use is lim-
ited to very prolonged procedures, or when signifi-
cant inflammation or swelling is expected such as
maxillofacial alcohol injection. In these cases, dexa-
methasone 10 mg is given intravenously (bolus) fol-
lowed by a maintenance dose of 8 mg every 8 hours
tor the tollowing 3 days.
Catheter induced vascular spasm can be an unde-
sirable event during endovascular procedures in the
ECS and it is usually triggered by mechanical stim-
ulus. Percutaneous administration of nitroglycerin
(nitropaste) is a useful treatment without significant
systemic reaction such as hypot
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Countee TW, Vijayanathan (1979) External carotid artery in
internal carotid artery occlusion: angiographic, therapeu-
tic and prognostic considerations. Stroke 10:450-460
Djindjian R, Meriand II ! I 97SjSuperse!ective arteriography
of the externa! carotid artery Springer, herkn Heidelberg
New York
Kuru Y (1967) Meningeal bi a n.c lies of I lie ophthalmic artery.
Acta Radiol 6:241-251
Lasjaunias P (1986) The external carotid artery: functional
anatomy. In: Taveras }\', Ferruci ]T iec.s : Radiology, chap
99. Lippincott, Philadelphia
Lasiaumas P, Berenstein A, Doyen f 1 i 1 "79 i Functional anat-
omy of the facial artery. Radiology 1 33:631-638
Lasiaumas P. Doyen I" 1 i 1 97? : The ascenc.mg pharyngeal a.t tery
and the mood supply of the lower crania! nerves. I Neuro-
radiol 5:287-301
Lasjaunias P, Berenstein A, Ter Brugge K(eds) (2001) Surgical
neuioangicgriipl'.y, clinical vnsctdar anatomy and varia-
tions, vol 1. Springe:. Heihn l-leiclciberg New York
OsborneA (ed) il994i I'ntgnosiic nenioriiJiology. Mosby, St
19 Endovascular Management for Head and Neck
Tumors
Paula Klurfan and Seon Kyu Lee
Nasopharyngeal Tumors 247
[uvenile Angiofibroma 24S
Classification 248
Armiomii." Features 248
oiiaj ms; rir-.iiu:'e:S 248
Natural History 249
Diagnosis 250
Treatment 250
Embolization Technique 250
P:ir;ig;i:;gJomas 251
Classification 251
Pathology 251
Imaging 252
Treatment 252
T'lyrolamigeal Tumors 254
Craniofacial Tumors 254
Miscellaneous Applications of Embolizatio
Therapy in the Head and Neck 254
Preoperative Embolization 254
f jin M/.nngeraent 255
Hemorrhagic Emergencies 255
Cookbook 255
References 256
Head and neck tumors consist of primary tumors
arising from various regional tissues including
lymph nodes and metastatic lesions. Most of these
lesions are highly vascularized due to both abun-
dant vascularities of the head and neck region and
their histological types.
Magnetic resonance imaging (MR1) is the most
useful imaging study for the initial evaluation of
head and neck tumors. Computed tomography (CT)
is also helpful in defining the anatomical disposi-
tion of these lesions. In addition, the CT can pro-
P. Klumam, MD
Interventional Net: o:-: ad [.:■;■ >gv 'Iliiiii-.il FcKow, I'vpniimenl of
Mediciii Imaging, Univer^itv of Toronto, Toronto We^et n Hos-
pital, 399 Bathurst Street, Toronto, Ontario, Canada, M5T 2S8
S. K. Lee, MD, PhD
Assistant Professor a:'.d S i-.i ft' Neiu oj ;i.d :ologist. Department oi
MedsCLii Imaging, Univei^itv of Toronto, Toronto Ues^et n Hos-
pital, 399 Bathurst Street, Toronto, Ontario, Canada, M5T 2S8
vide important complementary information such
as the presence of calcifications and the extent of
bony involvement. Diagnostic angiography is hardly
used as a diagnostic purpose. In fact, its main role
is a carrier for the endovascular procedures for head
and neck tumor managements. Endovascular proce-
dures for head and neck tumors consist of (1) selec-
tive devascularization procedures of the feeding
arteries such as transcatheter arterial embolization
and (2) adjunctive embolotherapy including intra-
arterial chemoembolization. Functional vascular
embolization such as intra-arterial chemotherapy
for malignant head and neck cancers to maximize
local concentration with minimized toxic effect has
also been studied, however, further investigations
are necessary lor its clinical application.
19.1
Nasopharyngeal Tumors
Juvenile angiofibroma (IAF) represents 0.5% of the
head and neck tumors [1] and 15% of nonepithelial
tumors of the nasal and paranasal cavities [2]. It is
the most common benign tumor of the nasopharynx
and is typically d iagnosed on adolescent males, with
a peak age of 14-17 years. However, up to 20% of
these tumors are diagnosed after the age of 20 [3].
The most frequent clinical presentations of juvenile
angiofibroma are nasal obstruction and recurrent
nose bleeding. These symptoms can be followed
by sinusitis, otitis, hearing loss, or anosmia. Life-
threatening massive nose bleeding can occur and
is often difficult to control with nasal packing. In
these cases, it requires urgent endovascular treat-
ment after blood transfusion and establishment ol
diagnosis. The growth of JAF seems to be influenced
by hormonal activity, although tumor samples fail
to show the presence of estrogen, progesterone, or
androgen receptors.
Tumors developing in the nasopharyngeal region
in the adult population are most likely to be malig-
P. K.LirL-ii .-:-J J. K. L?t
nant. Infra-arterial embolization may play a signifi-
cant role when performed prior Co diagnostic biopsy,
radical excision or palliative treatment.
The angiographic and therapeutic protocols
e applicable to other hyper-
i region. Percutaneous embo-
i described to be effective in
:e or recurrent epistaxis from
is previously irradiated,
icluding panijifins'lii
described for JAFi
vascular tumors of thi
lization has also
the treatment of
nasopharynge;
Benign
roblastomas, esthesioneuroblastomas, hemangio-
pericytomas, and hemangioendotheliomas (most of
them are considered malignant) may be diagnosed
in the nasopharyngeal region. These tumors are all
generally highly vascularized and have a relatively
benign course. The treatment strategy for these
lesions is a radical surgery whenever possible and
therefore they will also be benefited from presurgi-
cal embolization.
Extracranial meningiomas are very rare (1%). In
some cases they may be located in the parapharyn-
geal space even though most of the tumors within
this location are benign salivary grand tumors or
neurogenic tumors like schwannomas.
19.2
Juvenile Angiofibroma
19.2.1
Classification
Several grading systems of JAF have been presented
but theFisch classification [] is the most extensively
used one. Fisch classifies JAF into four types. Fisch
type 1 is when the tumor is limited to the nasophar-
ynx and nasal cavity without bony erosion. Fisch
type 2 defines a [AF that invades the pterygomaxil-
lary fossa and the maxillary, ethmoid and parasellar
region but remains lateral to the cavernous sinus.
Type 3 is defined as JAF tumors that invade the
infratemporal fossa, orbit and parasellar region but
remain lateral to the cavernous sinus. Finally, the
type 4 tumors are those that sh<
of the cavernous sinus, the optic chi
the pituitary toss;).
19.2.2
Anatomic Features
JAF is a highly vascular and locally invasive tumor.
It is usually originated from the superolateral aspect
of the choana, near the spheno-palatine foramen,
but may also arise more medially, near the vomer,
from the pharyngeal roof where it involves the body
of the sphenoid bone, or from the adjacent pterygoid
plates.
Regardles
tumor has a significant v
five activity. It may cause
even though the JAF does
sues directly. Attached to
structures, it extends throi
into the adjacent oper
itological origin, this
ascularity and prolifera-
significant bone erosion,
not invade the bone tis-
the neighboring osseous
igh the submucosal space
:es. Macroscopically, JAF
is reddish-gray or red purple in color and has a firm
rubbery consistency with a tabulated shape. Multi-
focal tumors have never been reported.
19.2.3
Imaging Features
Imaging (CT, MRl) studies usually show the pres-
ence of an expansible lobulated lesion located at the
nasopharynx. Due to the local extension of the JAF,
it can show significant bony erosion expanding into
the surrounding nasopharyngeal cavities, maxillary
sinus, and sphenoid sinus and infrequently to the
anterior skull base and the orbit (extra- capsular
and extraconal). MRI is an excellent complemen-
tary study for JAF evaluation. Intracranial invasion
and intradural tumor extension can be evaluated
and certainly is a decisive factor to determine radi-
cal treatment. MRI is also useful to differentiate
tumor extension into the sinuses from sinusitis.
The contrast enhanced MRI also shows extensive
enhancement of tumor due to its hypervascularity
(Fig. 19.1a). Contrast enhancement is essential for
the JAF CT examination. Reviewing CT scans with
both soft tissue and bone window setting is nec-
essary to evaluate the extent of the tumor as well
as bony erosions. Coronal and axial views provide
good anatomical information regarding the rela-
tionships among tumor, nasopharyngeal soft tis-
sues and osseous structures of skull base. On CT,
the JAF usually shows displacement and thinning
of bony structures without definite bony destruc-
tions considering the size of main mass (Fig. 19.1 b).
These are useful radiologic findings to differentiate
the JAF from other malignant tumors in children
r Management for Head and Neck Tumors
Fig.19.la-f. TAF:An 18-year-old male presenting wfth epuftaxts. Trie MR] and the CT scan shows orbital
tempor.U iossM extension of tumor ivi:h t^gnilioan- Pony erosion :.a,b:. Aneiogiam sfiovo; viimof.U ir>l:;sli arising l~r.:- ni Ih.e
intern.:! maxillary .irtery, ;he facial aioc-rv and the ascrndiisg pharyngeal .irtery li-fj. Preoperative emPo.izaiion with panicles
wjf perfoimed afler s tie." nvc- cailieteiiz;'.! ion of tiie feeding aneiies. Courtesy of Dr. K. terBrugge
such as rhabdomyosarcoma that typically destroys
adjacent bony structures.
On angiography, the JAF presents with a dense
tumor blush (Fig. 19.1c}, and this is highly accurate
to delimit tumor extension. Although it has intense
hypervascularity, angiosivipluc iiruiings of arterio-
venous shunting or early venous drainage have not
been reported. Feeding arteries of JAF are mainly
external carotid artery (ECA) branches such as
distal internal maxillary branches, accessory men-
ingeal artery, superior pharyngeal division of the
ascending pharyngeal artery and the ascending
palatine artery.
Internal carol id artery (ICA) may supply the JAF
without having intracranial portion of the tumor.
However, if angiographic tumor blush is located
above the skull base on AP and/or lateral views and
has vascular supply from the ICA branches and/or
from ascending pharyngeal and/or proximal inter-
nal maxillary arteries, it might represent intra-
cranial extension of the tumor. However, the sub-
arachnoid space extension of tumor is exclusively
supplied by the ICA branches. The evaluation of the
venous phase of the internal carotid angiography is
an essential part of diagnostic angiography, since
it will demonstrate the patency of the cavernous
sinuses and adjacent venous plexus those will affect
surgical respectability of the tumor.
19.2.4
Natural History
Osborn and Friedman suggested that repeated
hemorrhages within the tumor could stimulate the
formation of granulation tissue and a fibrous reac-
tion (1). This would explain some cases present-
ing spontaneous regression and tumors that tend
to have a slower rate of growth after adolescence
due to a higher proportion of fibrous tissue and
less tendency to bleed. As the disease progresses,
facial deformities, proptosis, blindness and cranial
nerve palsy may occur. Thus, complete spontaneous
regression of these tumors should not be expected
P. K.LirL-ii .-:'J J. K. L?t
and treatment should not be delayed due to the
tumor's potential to behave aggressively.
The recruitment of new vascular supply is proba-
bly related to the production ofangiogenetic factors
and it may explain the local i
types of the JAF.
19.2.5
Diagnosis
The diagnosis of JFA is mainly based on a careful
clinical history and nasal endoscopic examination
in addition to the imaging studies (CT and MRI).
Biopsy to establish liistologic.il diagnosis is not
indicated, and definitive diagnosis can be estab-
lished by angiography, which certainly will play
an important role in the patient management and
treatment.
19.2.6
Treatment
The objective of the treatment is complete :
of the tumor. Surgical removal and radiation therapy
are considered as the best therapeutic options. Con-
troversy still exists as to how patients with recurrent
or residual disease should be treated and how large
tumors of the skull base should be managed.
Surgical techniques have been mostly successful
by using advancing endonasal techniques with the
use of the microscope for limited mid face degloving
procedures but in a small group of cases: transpala-
tal, lateral rhinotomy and craniofacial approaches
can be used.
Tumoral resection ot I A ]- may be challenging and
can be limited due to the risk of profuse intraop-
erative bleeding and the size and extension of the
tumor.
To diminish these risk factors and to facilitate the
surgical resection, preoperative intra-arterial embo-
lization, radiation therapy and exogenous estrogens
has been largely used.
Preoperative exogenous estrogens have shown to
produce positive effects on the bleeding rate. How-
ever, the morbidity cause by the administration of
such drugs to an adolescent male population is very
high, with consequences on the gonadal develop-
ment and function, which turns this treatment into
an undesirable choice.
Radiation therapy is known to produce partial
tumoral mass reduction or at least a significant
arrest of the tumor growth (80%), but functional
morbidity and the high rate of long term secondary
neoplasm induction place this treatment option in a
secondary role. Thus, in general, radiation therapy
for JNF is restricted to certain cases where intracra-
nial extension prevents a complete resection of the
lesion. Its effects are secondary to post radiation
vasculitis and not the targeting of the cellular com-
ponent. The use of radiation as a sole treatment has
shown an overall rate of recurrence of 20%.
Intra-arterial embolization has resulted in a help-
ful and reliable technique in preparation for surgery,
and currently is the preferred combined treatment.
This procedure, when performed by an experienced
team carries no significant morbidity or mortality.
Reported complications or unsatisfactory results are
likely related to insufficient training or knowledge
or poor judgment during the procedure itself.
Based on the classification of Fisch, most sur-
geons in the international literature tend to operate
on stages 1 and 2, some on stage 3 and few on stage
4. The overall mortality of [FA is 3% and the rate of
recurrence after surgery varies trom 12% to 35% and
is likely owing to inadequate surgical removal.
Radiation therapy should be reserved for bilateral
cavernous sinus involvement and for the situation
where adequate surgical or therapeutic angiographic
teams are not available in a given geographic loca-
The use of surgical tumor resection precede by
intra-arterial embolization has shown strong evi-
dence in terms of reducing the number of recur-
rences and repeated recurrences as a consequence
of a reduction of the tumoral size and intraopera-
tive bleeding, and therefore a higher rate of complete
surgical resection of the JFA.
19.2.7
Embolization Technique
During preoperative angiography, major feeding
vessels arising from the external carotid system are
superselectively embolized and subsequent surgery
can be scheduled within 12 to 48 hours after embo-
lization.
The goal of the endovascular procedure is todevas-
cularize the tumor at the level of capillary bed, not
just proximal occlusion. Arterial supply of the tumor
mayvary depending on the site of the tumor and these
vessels can only be moderately enlarged. The internal
carotid artery supply to the tumor is usually the most
important factor to limit the capacity of pre- operative
Endovascular Man.'.gemear for Head and Neck Tumors
embolization. Therefore it is recommended to begin
the study by performing a contralateral injection of
the ICA with cross compression in the Caldwell view
followed by an ipsilateral ICA injection. This will
show the tumor's ethmoidal, sphenoidal and middle
cranial fossa extension. If the ICA branches can be
purchased easily and can get a safe position for the
embolization, there cannot be any restriction for the
procedure. However, in general, it is technically chal-
lenging to obtain a safe enough position to embolize
JNF thru the ICA branches.
Regarding the ECA branches embolization. Spe-
cial precaution has to be taken to identify potential
anastomosis between branches of the internal max-
illary and ascending pharyngeal arteries and the
intracranial or intraorbital arteries, and internal
carotid artery supply to the tumor.
For the last years, 150-250 urn in size polyvi-
nyl alcohol (PVA) has been the material of choice
to reach the tumor capillary bed during the endo-
vascular procedure. Smaller particles (50 (am) have
shown to pass through the capillary vessels reaching
the lungs with no therapeutic impact. Embolization
can be completed by the injection of Gelfoam pled-
gets (3 mm in caliber and up to 1 cm in length) to
achieve a transient devascularization of the region
(ligation) and in add it ion facilitate the distal throm-
bosis within the tumor itself.
Strong evidence indicates that presurgical embo-
lization facilitates surgical resection of JNF. Fur-
thermore, either embolization alone or emboliza-
tion associated with estrogens favors patients that
present surgically unresectable tumors due to size
The endovascular management may require the
usage of other techniques such as injection of fluid
materials such as NBCA or alcohol with flow con-
trol thru the internal maxillary artery or ascending
pharyngeal branches. Sacrifice of the ICA can be
considered on an individual basis in patients with
intra caver nous extension.
In this last case neurologic examination as '.veil as
a transitory carotid occlusion test should always be
carried out before the procedure.
The endovascular treatment results in a sig-
nificant benefit for the ]AF treatment whether it is
preoperative or palliative. Usually shrinkage of the
tumor mass can be observed both radiological and
clinically within 12 hours after the procedure and
breathing is usually improved indicating the return
of nasal patency.
19.3
Paragangliomas
19.3.1
Classification
Paragangliomas, glomus tumors, chemodectomas,
neurocristopathic tumors or nonchromaffin para-
gangliomas are several names that have been given
to the neuroendocrine neoplasms arising from the
neural crest derivates.
Thesetumorspresentwithawiderangeof locations:
tympanic, jugular; carotid, vagal, laryngeal, nasopha-
ryngeal and orbital. Tympanic and Jugular paragan-
gliomas are classified as temporal paragangliomas.
Branchial paragangliomas are found in a vari-
ety of locations in the head or the neck with almost
one half arising in the temporal bone. These are
the most common tumors of the middle ear. Its fea-
tures include multicentricity and frequent associa-
tion with other neural crest tumors. Other frequent
locations are: jugular, carotid, vagal, laryngeal,
nasopharyngeal and orbital, but pure single local-
ization is uncommon and paragangliomas are usu-
ally found to extend to multiple regions. Almost all
of the paragangliomas located in the head and neck
develop from a pre-existing normal paraganglion.
The clinical presentation of paragangliomas is
related to the location of the tumor (mass, bruit, pain
or cranial nerve palsy] and is usually progressive.
The malignant potential of paraganglioma is
reported as between 10% and 18% on the vagal,
carotid and laryngeal locations while in the tem-
poral area is about 3%. Spontaneous regression of
paragangliomas has never been reported. It usually
has a slow growing rate but in some cases can be
rapid or associated with additional tumors in other
19.3.2
Pathology
Depending on the location, the paraganglioma may
be lobulated or oval in shape and histologically it
consists of a capsulated, highly vascular stroma
with a paraganglion structure and epithelial cells
(Fig. 19. 2h). An irregular narrowing of the internal
carotid artery can Lie seen in some cervical paragan-
gliomas but is similar to tumoral encasement and is
probably not specific.
The ascending pharyngeal artery is a unique
link be tween parasansliomas in various territories.
P. K.LirL-ii .-:-J J. K. L?t
The tympanic, jugular, vagal, carotid and laryngeal
locations of paragangliomas are supplied by differ-
ent branches of the ascending pharyngeal artery.
The internal maxillary artery and the superior and
inferior laryngeal arteries are also responsible for
supplying paragangliomas in their respective ter-
Diagnosis of a carotid cai
performed by detecting expansive mass and bone
destruction on the carotid canal on the CT scan
associated with a narrowing of the intrapetrosal
carotid artery at the angiography.
19.3.3
Imaging
CT and MRI are important methods for the ini-
tial evaluation of a paraganglioma. Even though
the findings are usually not specific for this tumor
and may mimic other nerve sheath neoplasms,
these studies are highly effective to demonstrate the
extension of the tumor into different regions like
the carotid canal, the inner and middle ear, mas-
toid process, posterior fossa or pterygoid muscles.
(Fig. 19.2a,d,e)
These studies should always be performed with and
without contrast enhancement and a bone windowed
as well as a soft tissue windowed evaluation of the
CT scan of the lesion should be done. Direct coronal
images are indispensable in the presence of cervical
or skull base mass lesion and 1 to 3 mm sections are
required for the petrous temporal bone evaluation.
Due to the hypervascularity of the paragangliomas,
intense homogeneous enhancement of these tumors
occurs following the contrast administration.
Superselective angiography still represents the
most reliable study for pre treatment evaluation of
paragangliomas. If the diagnosis is suspected, the
angiogram should be performed before any biopsy
attempt. (Fig. 19.2b,c,f,g)
The topography of the lesion will always indi-
cate the arterial supply to the tumor. This could
consist of a single artery or multiple vascular sup-
plies. Angiography findings are usually an intense
tumoral blush, enlargement of the arterial feeders
and rapid venous filling. Just like in JAF, it is recom-
mended to perform the endovascular treatment at
the time of the diagnostic angiogram, whenever it
The principal arteries that should be studied
include the ipsilateral vertebral artery, the internal
carotid artery, the distal external carotid, the pos-
terior auricular, the occipital arteries and bilateral
ascending pharyngeal arteries. It is important to
visualize the venous drainage pattern and recognize
the presence of a venous thrombosis.
19.3.4
Treatment
Interdisciplinary management has shown to be criti-
cal for the optimal treatment of paragangliomas.
Even though complete surgical excision has shown
to be the treatment of choice, radiotherapy and
endovascular embolization have become important
therapeutic options for treating unresectable tumors
and perform palliative treatment. Preoperative pro-
cedures such as embolization to reduce the surgical
procedure timing and the bleeding risk contem-
plated in surgery have become an important thera-
peutic tool for these tumors. Endovascular emboli-
zation, when performed by an experienced operator,
is a highly efficient and a low-risk method.
The efficacy of radiotherapy is not clear. Several
studies have shown a tumor control rate as different
as 90% and 25%. The mechanism of treatment is due
to its effect on the vascular component causing vas-
cular arteritis and fibrosis rather than affecting the
tumoral cells. Brain tissue necrosis is an undesirable
side effect related with this method and is usually
detectable by CT or MRI.
Embolization of these tumors is usually per-
formed with 200-350 microns in size polyvinyl
alcohol (PVA). After particle injection, ligation of
the arterial supply can be performed with Gelfoam
strip injection. This will facilitate (he intratumoral
thrombosis. Liquid embolic agents are usually
reserved for palliative lesions and only when strict
flow control can be achieved.
As in any endovascular embolization of the cra-
niofacial region, special regards must be taken
towards the multiple anastomosis channels between
the ICAand the orbit, middle meningeal or occipital
arteries. As was previously described, the emboliza-
tion of the ascending pharyngeal artery with fluid
agent may induce lower cranial nerve palsy.
Endovascular Management for Head and Neck Tumors
Fig. 19.2a-h. Carol id body tumor lii-ti. i^T soan a shows the anatomioal relationship o: the aimoi wiih the oaroitd artery,
donnas rumor typioally shows enhancement .-tie: oo:i- rast administration. 5eleo:ive ai'.gi' 'giaphv b,e shows aimor blush aris-
ing l':'.::: siu.il] '-''. A bi anohes. "-!■■ iv.li-. r.:iti!,::r : d -h j Mk! shows liie tui )]■:■: .ooaiioi! in ; car. kinship wj::i Ihe petrous none and
".he iugiLai bub d,e Seleoiive ai'.gfagiaphv snow? Limo-: plush sapo.ieu by :lic postal ior au: ioular artery i fi a no tlie a so en Ping
oaa: vngeul ;.: :iriv :g:. baiholoeio e\ami:va:io:'. ih: dciv.onstjaies r.imo; tissue witli the ivpioah oapsulaled si: uor.ire and erpheahV.
oells sui roui'.dro with a vasoularizcu slroma. Com tesy of Dr. K. terBrugge
P. K.LirL-ii .-:'J J. K. L?t
19.4
Thyrolaryngeal Tumors
Tumors located in the thyrolaryngeal reg
usually malignant and highly vascularized. Even
though cerebral angiography and endovascular
embolization can offer a significant help for the
management of these tumors, most of cases are not
referred for either diagnostic or therapeutic angi-
ography.
P ret he rape u tic evaluation of the thyrolaryngeal
tumors should include conventional radiograms, CT,
ultrasound and radionuclide scanning. The highly
vascularized tumors of this region are usually sup-
plied by the superior and inferior thyroidal arteries
and are the most likely involved in the endovascular
treatment. These arteries are usually widely selected
for endovascular embolization of other head and
neck tumors due to the collateral supply to the lloor
of the mouth and the carotid region.
They even may be the only supply to the floor of
the mouth when there is a proximal ligation of the
linguo-facial system.
Except for large tumors, the non-invasive tech-
niques have shown little help in anatomical local-
ization of parathyroid tumors, especially through
the detection of secreting hormones at the neck
Endovascular management techniques for these
tumors include the superselective injection of 2 to
30 ml of contrast material [] with a higher dose of
iodine compared to the conventional dose for cere-
bral angiography. The persistence of the tumoral
stain indicates the local damage of the tissue, and
can be noticed for hours or days. After the proce-
dure, a reduction in the calcium level in the blood
can be found as a result of the released hormone
from the cellular granules. Even though a signifi-
cant result can be obtained from this technique,
the endovascular procedure should be considered
incomplete without a surgical excision. Experience
on particle embolization for parathyroid adenomas
has shown only a temporary effect and recurrence
is always noticed. No evidence has been reported on
the use of selective injection of cytotoxic agents.
Some of the vascularized tumors that have
shown to be beneficed by a preoperative emboli-
zation include: soft tissue and bony hemangiomas
in adults, capillary hemangiomas in children and
malignant synoviomas.
As previously described, some para^anijliom:.^
may be presented in the pharyngeal and thyroidal
regions and may require preoperative endovascu-
lar embolization for complete excision. Particles of
Liquid agents may be used as an only treatment for
palliative management of these lesions.
19.5
Craniofacial Tumors
Endovascular techniques certainly have a role in the
management of craniofacial tumors. Most of these
lesions are metastasis or primary malignant tumors.
The main impact of the procedure is the necrotic
changes in the tumor territory and this leads to a
significant size reduction in its mass. Rarely in these
cases, embolization is used as a single treatment,
like recurrent or non-surgical lesions, and reaching
as much of the area of the tumor with minimal side
effects is the main goal.
Some techniques can be used to maximize the
effect of particle embolization, like rearrangement
of the vascular supply to the lesion. For this tech-
nique a lateralized tumor may be selectively embo-
lized to give priority to a single feeder. The feasibil-
ity of this technique varies depending on the tumor
extent, accessibility of the vessels and potential vas-
cular anastomosis. For example, either the ipsilat-
eral ascending pharyngeal or the internal maxillary
artery can be embolized with particles. The remain-
ing feeder is deliberately left open. Repeated angio-
gram after a few weeks will verify the redirection of
the tumor supply, witch can now be used for a more
aggressive treatment: liquid adhesive, powder, cyto-
toxics, ethanol, loaded microcapsules, etc. Although
little experience has been reported with these mate-
rials, significant decrease in the tumor masses has
been reported.
Miscellaneous Applications of Embolization
Therapy in the Head and Neck
19.6.1
Preoperative Embolization
Embolization has been described for the preven-
tion of hemorrhagic complications horn a planned
tumoral biopsy. Particle embolization preserves
the histoarchitecture and inmunohistoanalysis and
therefore is a safe material for the preservation of
the tissue for diagnostic purposes.
r Management for Head and Neck Tumors
19.6.2
Pain Management
Embolization for control of tumor related pain could
be performed in selected cases where decongestion
or tumoral mass reduction is thought to decompress
the surrounding tissues, resulting in a local pain
relief.
19.6.3
Hemorrhagic Emergencies
Craniofacial and neck malignant tumors usually
present with a highly aggressive local activity. Bone
destruction and ulceration are not uncommon find-
ings especially as a secondary effect of radiotherapy.
In some cases, invasion of vascular structures may
lead to a recurrent bleeding or severe hemorrhages.
In these emergencies initial clinical management
and manual externalcompression is usually required
until the patient can be treated (Fig. 19.3a). Diagnos-
tic angiography is a priority to determine the cause
for the carotid 'Blow out' syndrome. Aggressive
tumor invasion or pseudoaneurysm formation of
the neck or nasopharynx vessels are usual angio-
graphic findings (Fig. 19.3b-c). These are life-threat-
ening situations and special consideration must be
taken for the overall clinical status of the patient
(shock management, blood replacement, etc.) Mild
to moderate hemorrhagic event may be temporarily
treated with particles in the tumor capillary bed. In
some cases ligation of a terminal branch (nasophar-
ynx) or even the external or internal carotid artery
by endovascular means is required (Fig. 19.3). For
these purposes different kinds of material such as
detachable or pushable coils, detachable balloons or
liquid adhesives are highly effective.
ig.19.3a-c. Nasopharyngeal cancer wiih profuse bleeding ;rea:e; wiili covered s".eni ijonied^ 1 }. A 54-year-old female with
licv.inced nasopbaivnge-.il ciuicei presented wi:h mtriicuble or:.', .mc n.isal bleeding. Kighl KA ang.-: gram ;i show? pseucoa:'-
eurysm of disui] oerrosiu segiv.enl i.-i. 1 ivni. Covered sir: 1 .: is introduced and ,idf.:s:ed its posidon across tbe pse.:doane.iivs::i.
b A ros:-s:e:'.: angiogram, e shows complele ■ irchisjon of pse::doaneurysm
Cookbook:
2. Femoral arterial sheath: 5 or 6 Fr, 11 cm. If the
patient has a very tortuous abdominal aorta, you
1. Anesthesia: General anesthesia preferred but the
can use longer arterial sheaths (30 ~ 45 cm).
tumor embolization can be performed under
neuroleptic anesthesia if the patient is stable
3. Diagnostic catheter: 4 or 5 Fr angled Glider
and cooperative. In case of emergency such as
(Boston Scientific®) or Berenstein (Cordis®)
carotid blow-out syndrome or profuse and active
nose bleeding, you may perform the procedure
4. Guide wire: 0.035 or 0.038 inch Glider
under the local anesthesia.
(Terumo®)
P. K.uri.;ii .;:'d L=. K.Lee
5.Guiding catheter: 5 or 6 Fr Envoy (Cordis®) or
Guider (Boston Scientific®) 90 cm
6.Microcatheter:
a.Prowler 14 (0.014 inch) or 18 (0.018 inch)
microcatheter (Cordis®) for the particle
embolization,
b. Elite 1.5 (0.018 inch proximal and 0.011 inch
distal end) or 1.8 (0.018 inch proximal and
0.013 inch distal end} (Boston Scientific®) for
the NBCA embolization.
7. Microwire:
a.Tfansend Ex 14 (0.014 inch) (Boston
Scientific®) for the Prowler microcatheter
b.Mirage (0.010 inch) (MTI®) for the Elite
microcatheter
8. Embolization procedure should always be per-
formed under simultaneous subtracted fluoro-
scopic control.
9. Particle Embolization:
a.A bottle of 150 ~ 250 urn-sized PVA particles
mixed with 10~15 cc of contrast media
b. Inject the particle mixture with lcc Luer-Lok
syringe.
c. Intermittent flushing of microcatheter with
saline using another 1 or 3cc Luer-Lok syringe.
d.If you have any resistance during the
embolization or flushing, do not forcefully
inject the PVA particle mixture or flushing
saline but remove the microcatheter
completely and use a new one if needed.
10.NBCA (N-butyl cya no a cry late) embolization:
a. Mix the NBCA with Lipiodol according to the
vascularity and the degree of arteriovenous
shunting.
b.For the tumor without significant arterio-
venous shunting, less than 50% (usually 30%-
50%) of the NBCA mixture can be used.
c.For the NBCA embolization of the head
and neck lesions, you should obtain a
safe microcatheter position and know
potential external carotid- internal carotid
communication pathways to prevent
disastrous internal carotid territorial
. Mann WJ, Jecker P, Amedee RG (2004! luvenile Angiofi-
Ltc'ijs: '.".hanging suigijii! concep: ■over tlie List 20 yens.
Laryngoscope 114
. LnsMiinias P. Kej ensiem A. 7er Br.igge K i ! S.irgica! Neu ■
lOiingi.igrjphv, Vol. 2, Springer
. Osborne A (1994! [Hagnc-siic Neuroradiology; Mosby
. kosenvv.;s:er H ( 1 974! ;"domus iugulaie in mors. Proc Roy
5oc Med 67:259-1 64
. Apostol IV, Fiazel! E (196:"; juvenile Niisopi'.aiyngeiil
Angiofibroma: a clinical study. Cancer 18:869-978
. Au L: em one TB i I ; !81 .: Hemangioper.cyioma-like rumor
of the nasal cavity.Arch Otolaryngol 107:172-174
. Batsakis JG (1979) Tumor of the head and neck, clinical
.;;id p.'.tho-ogk";'.! c c-j j:ij ;i e r:i tjo n ■= . WiLi.;;V:S & Wilkin's. 2nd
edn.pp 296-301
. Batsakis JG, Jacobs JB, Templeton AG (1983] Hemangio-
periciloma ::if rlie m'.sal c.ivi iy: Electron- on; k Silidy and
clinical correlation;. I Laryng Otol 97:361-368
. Berg NO (1 950! Tumors aris.ng from "die tympi'.nic g^aiid
(gl'i'iv.us iiigiLaiis) .mo (heir different;,] I diagnosis. Act.;
Pathol Microbiol Scand 27:194-221
. Casasco A, Herbreteau E, George E, Tran Ba Huy P, Def-
fresne I '■. Meil.iisd "I : : 934; I 'eviiscii.ai ;?i;iion of cri'.nio-
f;i.:i;i. in m-.jrs by percutaneous r.imor puncnire. AINK An;
J Neuroradiol 15:1233-1239
. Christiansen TA, Duvall AJ, Rosemberg Z, Carley TB
(1980) Juvenile nasophjiynye.;. Jiigiofibror-.j. Trans Am
Acad Opdialmol Otolaryngol 78:140-147
. Cummings BJ (1980) Relative risk factors ir. I he treat mtt;:
of juvenile nasopharyngeal a iigiollh :v-.;r.
Surg 3:21-26
'_"u minings HI, Mend k. i-'it^p.i trick P, Clar i K. HarwouL
A, Keane T, Beale F, Garrett P, Payne D, R:der W ( I 984]
PriT.i'.iy r.'.duiion dierjpy for juvenile ;":.iH'['i;i. jngc.u
.;ngiofi ;"■[::■ ma. Laryngoscope t; 4:l 599-1605
. Doppman JL (1980) The localization and treatment of
p:if.Uh.v:i:::d adenomas by Jiigiogr.ipnic :e-.":'.!":iqiirs. Ann
Radiol 23:253-258
. Erickson D, Kudva YC, Ebersold M), Thompson GB, Grant
CS, Van Heerden )A, Young WE (2001] Benign paragan-
glioma;: '.'Lined present.; ii:: 1 n .;:id l;e.;tmem outcomes in
236 patients. J Clin Endocrinol Metab 86:5210-5216
. Ewing JA, Shiyely EH ( 1 981 ] Angiofibroma: a rare case in
.;;• r.deib" fe:v..;.e. Oioioryngol i-ieod Neck Sing ^• : :::':j-
603
. Farrior JB, Hyams V], Benke RH (1980] Carcinoid apu-
doiVi.i arising in j glomus iug;;!.ire minor: review of endo-
crine .'.ctivity in glomus iugiil.;:e ;umors. Lmvng. /score
90:110-118
. Goncalves CG, Briant TDR (1978) Radiologic findings
in ii.;sopliary:ige.;l angiofibromas. ■ il.in Assoc kadiol
29:209-215
. Harrison K (1 ^74! Glomus uiguli'.re :umors: their clinical
beh.;viof ;'.nd man.'.gemem. Proc Roy Soc Wed ti7:2i'4-
267
. Hertzanu Y, Mendelso
( 1 ,: S J ! H.;emai":g;.:'pr:.';
55:870-873
3, Kassner G, Hockman M
a of the larynx. Brit J Radiol
20 Embolization of Epistaxis
Georges Rodesch, Ho:
\ Alvarez and Pierre La
20.1 Introduction 257
20.2 Etiologies and Origins of ENT Bleedings 257
20.3 Clinical Piemen I iu ion and Initio! Management 258
20.4 Vascular Aniitomv mid Angiographic Protocol
of the Nasomaxillary Region 259
20.5 Technique of Embolization 259
20.6 Idiop nl i'.ii Hyistaxis 262
20.7 Traumatic Epistaxis 264
20.8 Tumor-Related Epistaxis 264
20.9 Epistaxis in Hereditary Hemorrhagic
Telangiectasia 266
20.10 Results ■:■:' Embolization Ti'.erapy in Epistaxis 267
20.11 Conclusions 267
20.12 "Endovascular management of EPX
from a Practical Point of View" 268
20.12.1 What Has to Be Expected from Angiography
in EPX? 26S
20.12.2 What Causes of Epistaxis Require Emergent
Treatment; 268
20.12.3 When Is Embolization Required in HHT
Disease? 268
Cookbook: Embolization of ENT bleeding 269
20.12.4 Whatls the Place of Surgery in Epistaxis? 259
References 270
20.1
Introduction
Epistaxis (EPX) is a nosebleed that can result from
various etiologies. This condition is rather common,
often benign and self-limit in;; [23], It may however be
the symptom of a n undc-i'l vi Lis; ].vii hi 'logical condition;
and it is therefore mandatory to diagnose properly its
origin in order to propose an adequate treatment [20].
Traumatic EPX is another common cause of serious
epistaxis resulting from maxillofacial trauma, and
can lead to massive life-threatening intractable hem-
orrhage from associated vascular tears.
obi
EPX has been described as the most frequently
ymptom leading to emergency i
ENT clinic [21]. Only 6%-10 %
of EPX require medical attention [19, 22]. Emboliza-
tion should only be reserved to patients who have
been preselected by a proper initial medical and/or
ENT evaluation and management trial [6] as well as
a radiological evaluation.
Etiologies and Origins of ENT Bleedings
The various reported causes of EPX are listed in
Table 20.1. They can be also be distinguished
according to the age group in which they develop
(Table 20.2)
Broadly speaking, one can categorize EPX into
two main groups [23]:
• Instances where an organic lesion is the source of
the bleed. Different pathological entities can be
recognized and specific treatments can be offered.
This requires a multidisciplinaiy approach to
achieve palliation or cure. Embolization is then
often only part of the global therapeutic manage-
ment required.
• Instances where no underlying wife alar or tumoral
pathology can be identified [2]. Inconsistent asso-
ziationwith arterial hypertension, smoking, alco-
hol consumption, or hypercholesterolemia can be
found. Most of these patients have been previously
healthy until presenting with acute EPX requiring
therapy. In those idiopathic EPX cases, the goal of
treatment is to control and stop the bleeding.
Another way to categorize EPX is bas
G. Rodesch, MD
Service de Neuroradiologie Diagnostique et Therapeutique, ing site, with two distinct types of EPX:
Ho pi la J Fixh,40 rue Worth, 92150 Suresnes, France
H. Alvarez MD; P. Lastalnias, MD PhD
Service de Neuroi-.idiol ogie Piagncstiq-ie ei 7s'.er;ipeu:iq'.:e,
Hopital Bicetre, 78 rue du General Leclerc, 94275 Le Kremlin
Bicetre, France
lthebleed-
Antcrior EPX: This is the most frequent type, and
is usually less severe than the posterior one. It
often resolves spontaneously. The bleeding site is
Table20.1.Mo:;i i'reqiii
Idiopathic
Heredi:.iiv heiiiorj'h.igic le^ingifi";
Arterial hypertension
TY.uariaasra
Coagulation disorder
Benign tumor
Iatrogenic i*u:'g:c;i!j vascalar tear ■
Malignant tumor
Aneinv;ni
Arteritis
Intracranial Va.SClLar niakonn-.i ; iOi'
Table 20.2. EPX: populations and n
Pediatric population Trauma
Tumors
Maxi Ho -facial surgery
Coagulation disorders
k'lderlv ivpiiiiiiio: 1 . Anticoagulant treatment
Arterial hyper reus ion
Avei'igr age peculation Idiopathic
HHT
P.: in c:s
Trauma
located in the anterior septum (on the plexus of
Kisselbach). If treatment is required, simple pro-
cedures such as compression, anterior packing, or
cauterization can usually easily arrest the hemor-
rhagic episode.
> Posterior EPX: This type requires more aggressive
or active treatment. Cauterization, anterior and
posterior packing, local sclerosis, local injections
of haemostatic agents, electrocoagulation, surgi-
cal clipping, and ligation have all been described
to control the hemorrhage [5, 13, 17, 23, 24]. The
patients usually poorly tolerate posterior packing.
They still belong however to the panel of neces-
sary ENT procedures that has to be attempted
before performing any embolization.
20.3
Clinical Presentation and Initial
Management
A recurrent EPX that does not stop spontaneously
usually leads to consultation with an ENT surgeon
or at the emergency room staff. Careful endoscopic
evaluation is then performed in order to delineate
the site and type of bleeding. A first treatment (cau-
terization or p;u km;; } is rat tempted. Even such simple
procedures can control the bleed, even though tem-
porarily. In severe facial trauma, anterior and pos-
terior packing might allow stabilization of unsteady
hemodynamic situations. This allows further clini-
cal evaluation, correction of the coagulation profile,
careful history and physical examination, and addi-
tional radiologic!.]] investigations to be performed
to better delineate the etiology and precise location
of the hemorrhage [23]. EPX can have other origins
than the nasal tossa: lesions in the frontal, sphenoi-
dal (Fig. 20.51, or maxillary sinuses can present with
EPX; middle ear hemorrhage can also be external-
ized via the Eustachian tube. Initial proper clini-
cal examination is thus mandatory combined with
evaluation of the angiographic findings and careful
analysis of the potential collateral circulation. Care-
ful preliminary evaluation will be more likely to lead
to a satisfactory diagnosis and treatment.
Packing stops the EPX but is often poorly tolerated
by the patient and, if prolonged, can lead to serious
complicated such as aspiration, sinus infection, and
necrosis by intranasal balloon pressure [23]. It has to
be therefore limited in duration. Packing is however
often a necessary step in the therapeutic manage-
ment of nosebleed and further therapeutic proce-
dures should be performed only if these initial ENT
treatments fail, and EPX recurs. Failure rates up to
25%-50% and complications rates of 20%-60% have
been described [17, 23, 24]. In these situations, one
considers the EPX to be intractable and mandates
other managements. External carotid artery ligation
has been proposed in the past but should currently
be avoided as the rich max illo- tana I collateral supply
will rapidly reconstitute distally the sacrificed arte-
rial trunk, leading then to clinical recurrences [1, 2,
10]. Moreover, further endovascular treatment will
then be more complex or impossible because of indi-
rect arterial supplies. Internal maxillary clipping or
ligation have also been reported [5,23], but with a
complication rate ol tip to 47% and clinical failures
of 15 % [13,17,23]. Rebleed can easily be explained by
the developments of anatomical collateral pathways.
Anterior and posterior ethmoidal arteries (aris-
ing from the ophthalmic artery), internal carotid
artery branches (inferolateral trunk, vidian artery}
and nasopharyngeal vessels (ascending pharyngeal
artery, descending palatine artery, ascending pala-
tine artery, accessory meningeal artery) will partici-
pate to restore the flow distal to the ligated internal
maxillary artery. However, the mere fact that proxi-
mal disconnection alone might be successful sug-
gests that the decrease of pressure and indirect flow
to the nasal mucosa might play a role in the physi-
ologic hemostasis that will occur [23].
i-.niLx'kziition of Epistaxis
Endovascular therapies have gained much popu-
larity nowadays. Embolization of EPXhas to be per-
formed according to strict angiographic protocols
taking in consideration the clinical situation and the
cause of the bleed [9]. This will be further illustrated
Vascular Anatomy and Angiographic
Protocol of the Nasomaxillary Region
The cavum and the nasal fossa, both located on
the midline, need bilateral explorations even if
the symptom or the disease seems to be unilateral
(Fig. 20.1). Exploration of adjacent territories will
help in delineating with accuracy the vascular limits
of a given lesion. A unilateral vascular approach
should therefore be avoided [1, 9, 10].
The distal internal maxillary artery is the main
arterial trunk supplying lesions in the nasomaxil-
lary area (9, 10, 23]. Vascular supply is via the sphe-
nopalatine artery of the internal maxillary artery,
the alar and septal bran-: lies of the facial artery.
The sphenopalatine artery originates from the
pterygopalatine segment of the internal maxillary
artery. It exits the pterygopalatine fossa through
he sphenopalatine foramen and penetrates in the
nasal fossa behind and above the middle concha.
It divides then in two trunks: a posterior lateral
nasal artery (or concha! artery) supplying the tur-
binates and parts of the maxillary, ethmoidal and
sphenoidal sinuses, and a posterior medial nasal
artery (or septal a itei v) supplying the nasal septum.
Anterior and posterior ethmoidal arteries arising
from the ophthalmic artery beyond its second intra-
orbital portion also supply this midline structure.
Ethmoidal arteries supply the superior parts of the
septum at the level of anterior and posterior eth-
moidal cells; they will build a rich anastomotic net-
work with septal arteries.
In its distal portion, the septal artery of the sphe-
nopalatine artery abandons the nasopalatine artery
that anastomoses with the terminal branches ot the
greater palatine artery through the distal hard palate.
The arterial supply to the inferior and anterior por-
tion of the nasal cavity is thus accomplished.
The contribution of the distal facial artery to the
v;i<,.t]l;in;:,ri]onoltbe nn^iiiia^ilkuy region depends
from alar arteries, and from anterior septal arteries
(branches of the superior labial arteries). This ante-
rior and inferior portion of the septum (the plexus of
Kisselbach) is thus an arterial junction between the
facial, nasopalatine and descending palatine arter-
ies [23].
Accessory supply to the nasal fossa and to the
cavum has been described in vascular lesions or
after proximal ligation via the accessory meningeal
arteries and ascending phan ngeal arteries [3, 23].
The nasal cavity is therefore a difficult area to
control by endovascular procedures because of the
complex arterial supply belonging to two systems:
the internal carotid artery via the ethmoidal arter-
ies, and the external carotid system mainly via
the sphenopalatine artery. Transarterial approach
to this region will mainly use the external carotid
artery vascular channels.
20.5
Technique of Embolization
Diagnostic and therapeutic angiography is per-
formed in the angiography suite, the nasal pack-
ing being kept in place and always after thorough
clinical examination of the pat lent by an ENT doctor
[23]. The whole procedure is performed under gen-
eral anesthesia (GA) for the patient's comfort. GA
also allows suppression of breathing during angio-
graphic runs, and eliminates agitation and uncon-
trolled motion. In addition, the patient airway and
ventilation are secured despite the nasal packing.
Indirectly, these measures lower the risk of vaso-
spasm due to intra-arterial catheter manipulation.
Conscious sedation and neuroleptic analgesia are
less frequently used because they lack the above
advantages of GA; it will be reserved mostly to
patients with contraindications to GA.
An introducer sheath is placed into the femoral
artery; its size will depend on the pathology sus-
pected: in case of rupture of the internal carotid
artery in adults, a large 6 or 7 F introducer sheath
should be initially placed to allow the use of large
size guiding catheters for the manipulation of
detachable balloons. In children, the smallest pos-
sible introducer size is initially inserted. In our
experience, all major nasomaxillary arteries and
main branches, which invariably represent the
pathology responsible for the EPX, can be catheter-
ized with a 4F or 5F catheter [23] (Fig. 20.1). Direct
puncture of the arterial branches or of the internal
or external carotid artery should not be considered
[1]. The embolization (usually with particles) is per-
formed through the same catheter, except if specific
G. Rodesch et al.
Fig.20.la-j. Twenty-live-year-old ivoiVj.ui with von Willebrand disease
suffering from recurrent EPX mainly originating from the left nasal
fossa despite medicjl treatment to correct her .loagulopiithy, and nasal
packing. Embolization was indicated because of failure of all other treat-
ments. The angiographic protocol for EPX is followed. The procedure
begins with injection of the right internal carotid artery a that shows a
faint blush in the .interior etljiiioiii.il region I ,; no ■•■■ j . The right internal
maxillary artery is catheienzed and contrast iniection in lateral b and
AP projections c only shews, a normal fain; mucosal blush on the turbi-
nates i asterisk) and nasal septum i sniitll -.incws). The internal maxillary
artery is emboli zed will: micro particles until distal disconnection of the
arterial territory is obtained d. A large snip of Gelfoam is then injected
to enhance the regional devasculanzation i noi shown I. The right facial
artery is then opacified, e: AP view! showing its contribution to the
vascularization of the alar (iin-Lnr) and anterior septa! regions [double
Embolization of Epistaxis
arrow). The right facial artery is embolized widi the same material fol-
lowing the same ruies. The nasomaxillary region on the left side is then
studied, with injection of the internal carotid artery showing faint septjl
hyperemia supplied ] cy die anterior ethmoid.;, arteries [f (lateral view)
and g (AP view): arrow]. The left intern. 1 . 1 maxillary artery supplied the
left nasal fossa [U (lateral view) an.: i !AP view): ijsh'nsk], and is then
embolized in the same manner. The left facul artery ij, lateral view) is
not embolized because or its hypoplastic territory th;:t does not partici-
pate to the vascularization of the alar zone. Note that embolization was
carried out despite the fact that no clear-ctii abnormality was detected
in the vascular tree or at the level of the nasal fossa. The ENT surgeon
was told that he might have to clip the ethmoidal arteries in case of
e of EPX because of the prominent r.spect or" these vessels. The
1. oack Lng was removed c4 his .ate:; the patienl did not present with
it EPX anymore
G. Rodesch et al.
Fig.20.2a,b. Young woman with a uimor o: the cheekbone. Angic-gi aphy was pel formed in orc!er to disclose- any hypervascu-
lariiv oefore surge! v. The >sio:'. was iivosluLli/ but opacif.ca;io:i of the internal maxillary ,n tei v in the Af a and la lei jI views
l> showed iniensie nasal rossa mucosal o!ush (<iit':>;.iki corresponding :t: ,1 no: ::.:.. appearance 1:1 o woman in the premenstrual
embolic materials are necessary (balloons or coils}
or if superselective catheterization is required in
case of anatomic variations that have to be respected
(e.g. meningo- ophthalmic artery). Other investiga-
tors [23] recommend routine superselective embo-
lization after catheterization of the sphenopalatine
artery; however, no differences in the immediate
outcomes and clinical follow-ups have been noted
between these techniques. Undoubtedly, the super-
selective approach is associated with higher cost,
and more time and labor, which is why we have
continued to favor the simpler regionally selective
approach since 1979.
20.6
Idiopathic Epistaxis
The initial study in idiopathic EPX should involve
the internal carotid artery ipsilateral to the bleed,
using both lateral and AP views in order to detect
any lesion of the petrous or cavernous segment of
this vessel. This also allows the evaluation of nasal
fossa vascularity that originates from the ethmoidal
arteries. Angiography ol internal maxillary arterv is
then performed in lateral views to depict any culprit
anastomoses with the internal carotid system, as the
external carotid origin of the ophthalmic artery. These
anatomical variations donot contraindicateendovas-
cular therapybutwillrequire superselective catheter-
izations in order to avoid any erratic emboli in the
internal carotid territory. Embolization is performed
with small size particles (250-350 micron) that will be
injected within the flow at each systolic pulsation until
stagnation of contrast is detected in the vessel. Large
strips of Gelfoam are secondarily injected in the inter-
nal maxillary artery in order to increase the distal
devascularization. Embolization should always begin
first with the most distal territory [2]. Second, angi-
ography of the ipsilateral facial artery is performed. If
contribution to the nasomaxillary territory is noted,
the facial artery is then embolized with large strips of
Gelfoam in order to reduce the flow in its distal region
and participate to the hemostasis.
The same studies are repeated in the contralat-
eral vessels, and embolization performed accord-
ing to the same rules. As a rule, proximal ligation
or occlusions with coils must be avoided, as they
will not properly control the bleed and will favor the
development of collaterals.
In our experience, the nasal packs are usually
kept in place for 24 hours and then withdrawn by
the ENT surgeon. Some teams advocate removal of
the packing at the end of the procedure in the angio-
graphic suite [23]. The patient will be seen for follow
up in consultation both by the referring physician
and by the interventional neuroradiologist.
Embolization of Epistaxis
Fig.20.3a-f. Young male with .in history of progressive nasal obstruction
it nosebleed. CT a and MR b conn mi a nasopharyngeal angiofi-
broma. Presurgical embolization is perfoimed: ang.oei aphy of the internal
carotid artery (c: lateral view) shows faint participation to the ethmoidal
vase L La i ity via the pos:erio: ethmoid a I arteries (si'.wr iiiracsj. The
nal maxillary arteiy (d. lateral vievvi and ascenon'.g pharyngeal artery (e,
is) injections confirm the typical hyperintei'.se capilhn v blush c:'
.il angiohbioiv.a (.inc. ir.O. Embolization was car: iec
o particles and stiips or Gelfoam. Como!e".io:' ai'.giogiaphv of .he
n carotid artery (f. lateral view: confirms the devascularizi
n all its compartmeiivs
Persistence of prominent ethmok
seen on the post embolization nnsiogiv
diet further bleeding, requiring surgi
of these arteries, as this type of recurre
il arteries usually shows a normal blush of the nasal
nmaypre- Embolization is performed according to the :
il clipping rules than described above combined with co
n not tion of the underlvmg 1 0,11:11 lop;] thy will help
be managed properly by additroti.il endovascular trol the bleeding [11]. Partial In r at ten! ion has to be
therapy. paid to the orbital anastomosis, usually patent in
EPX is a frequent complication of coagulopathy children, in order to avoiding erratic embolus that
mainly in the pediatric population. Angiography could give rise to visual complications.
Fig.20.4a,b. Patient with HHT disease suffering from recur-
rent HVX. Nasal to:;* J telant;ie."1..isias ;i:e v.isoiil.nized by both
septal and turbinate brnnohes or the internal ma.xilkiry artery
(lateral view a, snaill ,-m'i>irj) and by ethmoidal branches of
the onhl;',;iJiik" ar:e:y i later a I view b, small .
20.7
Traumatic Epistaxis
Traumatic EPX requires initial CT imaging to rule
out any skull base or maxillo-facial fracture that
could be linked to a vascular tear responsible for
the bleed (Fig 20.6 and 20.7). Damage to the internal
carotid artery could be diagnosed if the fracture
involves the carotid canal, or ii a subarachnoid hem-
orrhage is associated to the osseous trauma, where
rupture of the suprac aver nous portion of the inter-
nal carotid artery should be suspected. Traumatic
EPX is a life-threatening emergency, and can be
associated with severe hemodynamic instability. If
a history of serious vascular trauma is evoked in
the setting of severe EPX, superselective diagnostic
angiography should be avoided in order to prevent
rupture of a potentially associated arterial false
aneurysm, which is effectively the unclotted portion
of the hematoma associated with the vascular injury.
This represents a weak point that could rupture if
subjected to sudden increased pri
forceful injection. Instead, we recommend
situations that a nonselective runs
carotid artery territory be obtained in order to
depict angiographic signs of a vascular tear on the
internal or external carotid artery, including pres-
ence of a pseudo-aneurysm, localized vasospasm of
the affected artery, or truncation or even no filling of
the traumatized artery. It is important to know that
the exact localization of the rupture is best visual-
ized via the collateral circulation: an angiographic
protocol studying internal carotid, vertebral and
external carotid artery branches helps to built up
the regional vascular cartography and points thus
to the arterial leakage.
If the external carotid artery territory is affected,
sacrifice of the traumatized arterial segment is best
performed with glue in our experience. N-butyl 2-
cyanoacrylate (NBCA) is gently deposited proxi-
mally to the arterial tear or at the level of the stump
of the traumatized artery after superselective micro-
catheterization. Traumatic rupture of the internal
carotid artery is usually treated by sacrifice with
balloons and coils [7]. The recent availability of cov-
ered stents offers another endovascular alternative,
especially when occlusion of the internal carotid
artery is poorly tolerated [4].
20.8
Tumor-Related Epistaxis
types have been associated with
EPX, both benign (juvenile angiofibromas (Fig. 20.3),
angiomatous polyps, aipiilriry hemangiomas etc.)
and malignant (primary head and neck carcino-
mas, epitheliomas, metastatic lesions etc.). Tumor-
related bleeding tends to be recurrent and moderate
in severity. It may occur at night leading to anemia [2],
or be can associated with breathing difficulties due
to nasal obstruction. Life-threatening hemorrhage
is rare in these conditions but has been reported [2].
In the diagnosis of recurrent tumor-related EPX, the
patient usually first undergoes an MRI in order to
delineate the tumor location and extension. Angiog-
raphy and embolization are performed usually as a
Embolization of Epistaxis
pre-surgical procedure, or to control hemorrhage in
the rare occasion? ol lite-threatening EPX associated
with head and neck tumors. The goal of the endo-
vascular procedure is to devascularize the tumoral
capillary bed. All the vessels supplying the lesion
are studied according to an angiographic protocol
[9]. Angiographic patterns of primary and collateral
vascular supply are predictable in most cases, and
the location of the arterial feeders depends on the site
of origin of the lesion [2]. The moderately enlarged
vessels supplying the tumoral hypervascularization
should be emlx'lized with particles and Gelfoam: we
currently use small size particles (150-350 microns)
to embolize the tumor bed, as smaller particles may
pass through the tumoral capillaries and reach the
lungs [18]. The embolization is concluded by injec-
tion of large strips of Gelfoam in order to produce
a transient deva.si.Tili.in/.aiion of the region ,md
enhance distal thrombosis in the tumor. In case of
intracranial extension of the tumor, glue can be used
in order to selectively occlude any tumoral feeders
originating from the internal carotid artery. Balloon
occlusion of the internal carotid artery (to be con-
sidered only after proper evaluation of the collateral
circulation on arterial and venous phases} can be
utilized if radical surgical exclusion is planned in
large otherwise unresectable lesions [2, 23].
In our practice, we perform catheterization and
embolization using preset procedural sequences
that are applied in every external carotid artery
Eia. 20. >a t i. A !■ i .=■:.! <\.\ •■: jr.: -= . ni.: -: i L . < iir.ii;.,: by .-■::& .oi.." ,; ;h-j .i py ivh.o i.leve.opr.:. -lid. In; rl-'X. i. ":' a .;r.d \1 K b -honed
e marge mem of i he ieii cavernous sinus with ;'. slructure bulging hiio the spher.oio si mis i ■>: iiiioir: jii.i m irregular aspect of
ihe inlenj.il cr.rotio .irtery :b; iiriviri!. An infectious false aneiirvsivi was suspecied and ti'.e patieni underwent eiv.ergem .'nci-
ogri'.pi'.y. A left common carotid artery injection it, lateral view: confirmed the lesion i.e. -.uroif) on the c.vernous portion of
ihe .mei'iiiil carotid r.riery, which wr.s also stenosed. Sacrifice of ti'.e internal carotid artery Iwitj trapping of die oathologica.
zone) was performed with occlusion oalloons lij.'foii'Si after a satisfactory toierance test d
Fig. 20.6. Intractable HI-'X following ir.axi.ki facial and skull
base trauma. A common carotid ortery injection i lateral view!
shows r u pin re of the intern;'. I carotici a:: cry [large arrow) and
a spastic posttraumatic aspect or" the di;tal external carotid
artery Uinall arrows)
endovascuhir embolization procedure [2]. If several
branches must be embolized, one should always
tackle the most distill target first to avoid later loss of
access due to vasospasm. The next artery (arteries)
to be catheterized should include possible sources
of collateral circulations to the region embolized in
order to provide an alternate route to reach the ter-
ritory in case the embolization was too proximal.
Superselective catheterization of distal pathological
arteries is in our daily practice only performed if
Epistaxis in Hereditary Hemorrhagic
Telangiectasia
Hereditary hemorrhagic telangiectasia (HHT) or
Rendu-Osler-Weber disease (ROW) is a disorder that
presents with recurrent episodes of EPX. These epi-
sodes are difficult to manage because of the recur-
ring nature of telangiectasias (Fig. 20.4).
HHT is ,i dominant autosomal disease with vari-
able expressivity Ihat evolve 1 , usually in four stages:
latency, hemorrhages, telangiectasias, and anemia.
There are two genotypes recognized to date, HHT1
and HHT2, with a third one suspected (HHT3).
Endoglin is the gene that maps to chromosome 9q33,
which is mutated in HHT1, and which is thought to
be responsible for the telangiectasia, pulmonary
arterio-venous fistulas (AVPs) and cerebral AV
shunts [12]. Lack of endoglin, a binding protein for
transforming growth factor [3 protein, compromises
normal vascular remodeling in endothelial cells.
EPX is the commonest presentation of HHT both
in adults and children; however it may be not given
enough importance in H HT families and it needs to
be inquired about specifically. Cutaneous lesions are
accountable for 66.7% of the adults and 27.3% of the
pediatric population in our series, which is keeping
with its acquired nature and presentation in the 2nd
and 3rd decade [14]. Usually by the 4th decade the
telangiectasias will be visible [8]. The localization
in the mucous membrane is usually the one giving
rise to hemorrhages. The hemorrhagic manifesta-
tions in HHT have the following d istributions: EPX
85%, oral 20%, digestive 20%, genitourinary 10%,
lungs 17% [11]. Epistaxis is the major cause of death
in 4%-27% according to the series. The diagnosis
of the disease is mainly clinical, two of four criteria
being required: spontaneous recurrent EPX, typi-
cal mucocutaneous telangiectasias, positive family
history and typical visceral AVMs (cerebral, pulmo-
nary or gastro-intestinal [14]. Telangiectasias have
to be searched for carefully as they may be located
under the nails or on the tip of fingers or toes [11].
The family history may be poor as the penetrance
of the disease is variable, some families being not
affected by the disease but only transmitting it.
Appreciation of the evolution of the disease is dif-
ficult but of importance for the selection of the best
treatment. Complete cure is not possible nowadays
for this systemic disease; the only therapeutic objec-
tive is the stabilization of the bleedings.
We generally distinguish three stages in HHT,
which primarily reflect the disease impact on the
patient's daily life [11]. Stage 1: episodic EPX that
resolve spontaneously. Stage 2: periodic EPX some-
times following mechanical trauma, requiring no
more than one hospitalization and transfusion per
year, and allowing normal professional activity,
Stage 3: frequent spontaneous EPX requiring mul-
tiple hospitalization and transfusions per year with
resulting incapacitation or inability to lead a normal
lite. The therapeutic approach will depend on the
stage of presentation.. Stage 1 does not require any
treatment. Stage 2 should be treated whenever blood
transfusions are necessary. Stage 3 represents an
indication for therapy and usually requires a combi-
i-.mbokzation of Epistaxis
nation of both conventional EN'T procedures (local
treatments and scleroses, clipping of ethmoidal
arteries, etc..) and embolization that is currently
generally considered the better therapeutic alter-
native, albeit still palliative in nature, unless it has
been proven that collateral supply (mainly via eth-
moidal arteries) has developed.
Non symptomatic telangiectasias should not be
treatedln symptomatic HHT-reiated telangiectasias,
embolization with particles gives a satisfactory imme-
diate result with in) mediate hemostasis, last my tn:!in
3 weeks to 2 years in our experience. This reflects the
high angiogenetic activity of the disease and the con-
tinued development of new telangiectasias. Failure
to stabilize stage 2 patients, or to transform stage 3
patients to stage 2, will require the addition of more
aggressive treatments [1 1]. Estrogen therapy (at a dose
of 1-2 mg/day) has proven to be effective in the treat-
ment of EPX in this disease because of the specific
nature of nasal mucosa. Careful clinical and biologi-
cal follow up has to be performed in order to prevent
the side effects or complications of the treatment such
as gynecomastia in men, cancers of the endometrium
in women, phlebothrombosis, alterations of choles-
terol levels, etc...
Treatment of associated lesions in the brain, cord
or lungs has to be debated taking in consideration
Fig. 20.7. Massive H!-X wit:', hear 'dymuuic iiiS'.iihiatv following
n'.iixillofacial tra ■.:::': a. A large false aneurysm due to a vascular
laceration of the aista! :nlv:n.il maxilla j y artery (iiirari.'Aj is
detected. After microca:liele: ization of me pa:bologk\\l :uterhl
segment, it is embolized wi;h pio\i:::al glue deposition, with
rapid hemodynamic stabilization and control of the EPX
the natural history of the disease linked to HHT.
For example, the risk for hemorrhage seems to be
less for unruptured brain AVMs linked to HHT
(0.7%/year) compared to non-syndromic brain
AVMs (2%-4%/year}[12]. Endovascular treatment
of HHT-associated spinal cord a rterio -venous
fistulae (AVF) in the pediatric population has
to be offered, because of potential for neurologic
sequelae that can be linked to these lesions [15, 16].
Pulmonary AVF also require treatment because of
the hemodynamic symptoms they create, and the
potential for devastating neurological deficit asso-
ciated with thromboembolic diseases (strokes and
abscesses).
20.10
Results of Embolization Therapy
in Epistaxis
If properly performed, embolization allows imme-
diate hemostasis (about 97% of all patients in
our series) [1]. Recurrences occurred more com-
monly in HHT patients, requiring either addi-
tional endovascular treatments, or surgical clip-
ping of the ethmoidal arteries. Satisfactory stable
long-term results with no EPX are achieved in
86.3% of patients [1]. "Therapeutic Failures" with
recurrence of EPX is seen in 13.7% of embolized
cases, 75% of them being HHT patients, which
only reflects the aggressive angiogenetic potential
in HHT.
Procedure-related morbidity is rare, as are neu-
rological complications. Proper anatomic evalua-
tion can minimize the risks of stroke [23]. Careful
fluoroscopic monitoring, low pressure injection
of the embolic material and consideration of the
potentially dangerous anastomoses and vascular
supply to cranial nerves are mandatory to obtain
safe and effective results. In our series, complica-
tions occurred during the phase of diagnostic angi-
ography in older patients (0.4% and 1% permanent
and transient deficits, respectively) but were never
related to erratic emboli due to poor technical con-
trol during delivery of the embolic material, or to
lack of recognition of dangerous arterial anasto-
moses. Necrosis of the nasal septum occurred in
0.4% of cases. Non-neurological complications
include pain, trismus or facial edema that can be
sometimes described after these interventions but
have always regressed rapidly with analgesics and/
or corticosteroids.
20.11
Conclusions
Management of patients with EPX should involve
a multidisciplinarv approach. An escalating cas-
cade of treatment modalities offers these patients
a tailored approach yielding a high success rate
with minimal recurrences and low complication
rates [23]. Proximal vascular occlusion has to be
avoided, as are proximal surgical clippings. They
may reduce perfusion pressure to the nasal mucosa
but will not avoid reconstitution of the flow by the
rich collateralcircula t ion. Distalbilateralemboliza-
tion to achieve blockage at the arteriolar-capillary
bed level are essential for successful endovascular
managements of EPX. The effectiveness and safety
of the embolization procedure in trained hands has
currently rendered it the preferential modality of
treatment in intractable EPX. In idiopathic EPX,
devascularization of the posterior septal area is
emphasized, as this is the usual source of bleeding
hardly reachable for examination and cauteriza-
tion [23].
necessary to assess them properly in order to
manage appropriately these patients, by either
endovascular or surgical methods.
• Less frequently, mucosal hyperemia can occur in
women during the premenstrual period (Fig. 20.2).
EPX in those cases is usually modest and does not
require therapy most of the time. Intracranial
vascular malformations draining towards the
cavernous sinus and secondarily through orbital
veins may give rise to EPX: treatment of these
malformations relieves the bleedings thanks to
the secondary venous decongestion.
• In traumatic EPX the imaging signs are usually
more helpful and may help localize the bleed-
ing site. One has to look for a pseudoaneurysm,
,i] renal spasm or a missing artery. Hndovasailar
treatment should be targeted in priority towards
the bleeding zone.
20.12.2
What Causes of Epistaxis Require Emergent
Treatment?
20.12
"Endovascular management of EPX from a
Practical Point of View"
20.12.1
What Has to Be Expected from Angiography in
EPX?
• Angiography will rarely show active bleeding or
its cause. This should not precludes embolization
where clinical indications exist.
• A unilateral bleed, or a unilateral angiographic
localization of bleed should not preclude bilateral
embolization.
• The clinical, biological and imaging data orient
the diagnosis and will help to choose the appro-
priate material to use.
• In idiopathic EPX secondary to hypertension or
coagulation disorders, angiography is most often
negative. The aim of an angiography is then to
study the vascular 1 a natomy ot the skull base and the
inter- territorial and inter- regional anastomoses.
• In the case of HHT disease, telangiectasias are
detected at the level of the nasal mucosa. Bilat-
eral embolization will also need to be performed
in these conditions. Ethmoidal arteries are often
well developed in these patients and it is always
• The clinical suspicion of a ruptured internal
carotid artery (by trauma, surgical damage or sec-
ondary to a cavernous aneurysm) is an absolute
emergency, as is also the rupture of the external
carotid artery, even if the patient is hemodynami-
cally stable.
• In older patients suffering ol hypertension or
coagulation disorders (due to hepatic or hemato-
logical disorders or to anticoagulation therapy),
nasal packing and correction of the causative dis-
ease are usually sufficient to achieve hemostasis.
Failure of initial treatment requires complemen-
tary endovascular therapy, usually performed in
a less urgent context.
■ Presentation ol idiopathic HPX will often allow a
deferred embolization procedure.
20.12.3
When Is Embolization Required in HHT Disease?
Repeated embolization is usually necessary. In our
experience clinical remissions can last from few
weeks to years, and recurrences will usually require
new treatment. We perform embolization during
the acute phases of hemorrhage, when the bleeds
are too frequent and interfere with the quality of
daily professional or personal life, or when blood
transfusions are necessary [1, 11]. The long-term
Cookbook:
Embolization of ENT bleeding
Common EPX
(Idiopathic, coagulopathy, tumors, HHT..)
SFTerumo (children)
6F Terumo (adults)
Catheter:
4F Vertebral (Terumo)
In the case of failure (tortuous vessels e.g.): 4F Simons type II (Terumo)
Guide:
Glide wire 35 (Terumo)
Embolic material:
Contour particles 250-350 microns (Boston Scientific-Target)
Gelfoam (cut in strips)
If sup erselec five cc
Ihere.rization is needed:
(.".uidiiig call'.eiei : Hr.voy (Cordis) 5 or 6F
Guider (Boston Scientific-Target) 5 or 6F
Microcaiheter: Excelsior 18 or Excel 14
Microguide: Terumo 12 (45° or 90° angulation)
Mirage 008 (MTI)
Embolic m uteri ni: Contou: ;; a nicies l Bos ".en Scientific -Target)
150-250 urn
250-350 urn
Rupture of ICA
Introducer:
5F Terumo (children)
6F Terumo (adults)
Guiding catheter:
Envoy (Cook) 5 or 6F
Guider (Boston Scientific-Target) 5 or 6F
Guide:
Glide wire 35 (Terumo)
Micro catheter:
Minitorquer CIFN 130 (Mynvasis)
Embolic material:
Detachable Gold Vulve Bulbous 16 (Mynvasis)
If to be used in children, accciding tc age, weight, and size:
HvesiiiKiliy 4B inlioducei and Ar guiding catheter
If not: 5F introduce! and ?r guiding catheter
Preload system wiili jiiir.iioique: and dciachable balloons
Traumatic false ar
eurysm on external carotid artery
Introducer:
5F Terumo (children)
SFTerumo (adults)
Guiding catheter:
Envoy (Cook) 5 or 6F
Guider (Boston Scientific-Target) 5 or 6F
If needed in child ft'ii, aceidmg re age. ■■•■ eight, and size:
Possibly 4F introducer and Ar guiding cuke It; (4r Vertebral, Terumo)
Guide:
Glide wire 35 (Terumo)
Micro catheter:
Magic 1.8 or 1.5 (Bait)
Excelsior 18 or Excel 14 (Boston Scientific -Target)
Micro guide:
Terumo 12 (45° or 90° angulation)
Mirage 008 (MTI)
Embolic material:
NBCA (Braun Aesculap, Germany)
s of embolization is unpredictable. Emboli-
zation will be repeated as often as necessary and
possible. Clipping of the ethmoidal arteries and
estrogen therapy will be proposed when the ves-
sels responsible for the bleeds are inaccessible to
endovascular therapy.
20.12.4
What Is the Place of Surgery in Epis taxis?
> Clipping of the ethmoii
tive and relatively easy procedure to perform. It
should however be offered only after emboliza-
tion, or when the technical or anatomic condi-
tions are inadequate for success in endovascular
therapy, such as when the size of the ophthalmic
artery does not allow safe distal catheteriza-
> Ligature of the internal maxillary artery should
be avoided. The unilateral arid proximal aspect of
the procedure will allow the development of ipsi-
and contra -lateral anastomoses that will distally
reconstruct the vessel, and will continue to favor
rebleeding but without allowing subsequent selec-
tive auheteriz.itiom.
References
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Robin S,L;;sj.;uni;;s P i I W$\ Tranemenl en a. ova sen la ire ces
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21 Diagnosis and Endovascular Surgical Management
of Carotid Blowout Syndrome
., Walter S. Lesi
, and Shik-Wei Hsu
Background 271
Definition 273
Patho etiology 274
Diagnostic Evaluation 277
Endovascular Techniques 277
"Deconslr active" Techniques 27t>
"Reconstructive" Techniques 279
Outcomes 285
Future Directions 289
References 290
21.1
Background
The apoplectic consequences of a ruj
artery have been well recognized
dating back to antiquity. In both the distant and
near past, this catastrophe was exclusively the result
of a penetrating injury derived from an act of war-
fare or accident. Surgical intervention for treatment
of carotid rupture is also historically relatively old,
predating "modern" neurosurgical practice for more
than 100 years [1], John Abernathy, a former pupil
I.C.Ch.
i. Y I ■■
Director of Interveiilioii-.il NirUi-.iuidio.ogy. t'rofessor of Radi-
ology and Neurosurgery, University of lovva Hospitals ana
Clinics, University of Iowa Carver College of Medicine, 200
Hawkins Dr, 3893 JPP, Iowa City, IA 52242, USA
W.S. Lesley, MD
Chief, Section of Surgical Neuroradiology, Assistant Profes-
sor of Radiology, The Texas A&M University Health Science
M. Hayakawa, MD
Visiting Assistant Professc-i of Radiology. University of Iowa
Hospitals and Clinics, University oi Iowa Carver College of
Medicine, 200 Hawkins Dr, 3893 JPP, Iowa City, IA 52242,
USA
S.W.Hsu.MD
Visiting Scholar. University of Iowa Hospitals and Clinics, Uni-
versity of Iowa Carver College of Yedicme, jOO Hawkins Dr,
3893 JPP, Iowa City, IA 52242, USA
t Professor, Department of Diagnostic Radiology,
Chang C-ting Manorial Ho-soita!, Kaonsiiing, Taiwan
■ of the famed surgeon [ohn Hunter,
probably can be credited with the first well described
published account of successful surgical treatment
of a ruptured carotid artery in the late eighteenth
century [2]. The case involved a patient who suffered
a laceration of the internal carotid artery after being
gored in the neck by a bull's horn. Dr. Abernathy suc-
cessfully arrested the hemorrhage by simple ligation
of the artery, which fortunately was well tolerated
by the patient.
Although penetrating mechanisms of injury to
the carotid arterial tree still occur today, in more
recent times, physicians have been increasingly
confronted with carotid rupture or so-called "blow-
out" as an iatrogenic complication of surgical man-
agement of cervical neoplasms [3, 4]. The first well
described cases of carotid rupture occurring in
association with head and neck surgery date back to
isolated reports in 1962 by Borsdany [5], followed
by the first large case series published by Ketcham
and Hoye in 1965 [6]. The term "carotid blowout"
also was first coined during this time period by
Rutledge and Cagle [7].
The reasons for developing carotid blowout in
patients with head and neck cancer are potentially
multifold, being closely linked to the advent of
aggressive operative resections, flap mobilizations,
and adjuvant therapies for both primary and recur-
rent neoplasms. Occasionally, these interventions
may produce either direct or indirect trauma to the
carotid arterial tree, resulting in a cascade of events
that produce progressive structural fatigue and
eventual rupture of the affected artery. Owing to
the usual loss of anatomic fascial planes and barri-
ers from surgery, catastrophic hemorrhage through
various external and oropharyngeal pathways ulti-
mately ensues [4-6, 8-12].
Despite anecdotal reports of technical and clini-
cal success ol simple operative ligation for the treat-
ment of carotid rupture, most open surgical series
reported over the last few decades have shown
exceedingly high rates of mortality and morbidity
associated with this complication. Emergent opera-
J. C.Chaloupkai
tive ligation or attempts at primary repair/recon-
struction of the common or internal carotid artery
had been traditionally the only therapeutic maneu-
ver available lor 1 treating carotid blowout [3, 5, 7, 13-
20]. These approaches, however, generally resulted
inunacceptably high rates of major stroke and mor-
tality. A review of cumulative published outcomes
whereby carotid blowout was managed by surgical
ligation or repair/reconstruction revealed an aver-
age mortality ot approximately -40°o, and an average
major neurologic morbidity of approximately 60%
[3,4,6,11,12].
Several general limitations of operative manage-
ment of patients with carotid blowout may explain
this high morbidity and mortality. Patients suffer-
ing a carotid blowout often are hemodynamically
unstable, particularly in situations of uncontrol-
lable or protracted hemorrhage. In such scenarios
severe reductions in mean arterial blood pressure
and cardiac output may be encountered, which in
turn can lead to regional and global cerebral isch-
emia in susceptible patients (e.g. dysfunctional
autoregulation, lack of anatomic and/or physi-
ologic collaterals}. Adverse reductions in cerebral
perfusion pressure can be further exacerbated by
induction of general anesthesia, particularly in
patients with depleted intravascular volumes who
not infrequently will develop profound transient
hypotension in response to anesthetic. Extreme
blood loss from a carotid rupture not infrequently
produces a depletion coagulopathy that leads to
further uncontrolled bleeding (particularly in a
fresh operative wound). Extensive, often multiple,
previous surgeries in combination with either
external beam or intraoperative brachytherapy
radiation can make operative dissection extremely
challenging [4, 12, 15).
Another important limitation of past operative
series managing carotid blowout syndrome (CBS)
is that they were invariably performed without the
benefit of diagnostic angiography. Consequently,
the type and precise location of the hemorrhage
was often unknown, being mostly inferred from the
physical examination. Based upon our past cumula-
tive experience, a wide spectrum of anatomic loca-
tions for pseudoaneurysm formation involving the
carotid circulation likely would have been encoun-
tered in these series [4, 21]. This likely would have
resulted in frequently inadequate therapy of the
actual pathoetiologic mechanisms of hemorrhage
by empiric common carotid ligation.
An additional compounding proble
with conventional proximal carotid li
sk of thromboembolic complications
that may occur from the phenomenon of propagat-
ing thrombus within long arterial segments. Dandy
was one of the first to recognize that thromboem-
bolic stroke may occur after carotid ligation from a
growing tail of thrombus that often develops within
the large intravascular "dead space" distal to the
site of occlusion [22]. Historically, extensive clini-
cal experience with both open surgical and endo-
vascular parent artery occlusion techniques (mostly
for treatment of giant intracranial aneurysms) has
shown that "proximal" occlusions of the carotid
artery within the neck are associated with a rela-
tively high risk of thromboembolic stroke [23-27].
The risk of stroke from such a proximal occlusion of
the carotid artery also is likely to be increased with-
out the use of systemic anticoagulation for some
period of time immediately after carotid occlusion
[27, 28]. In the past it was likely that systemic antico-
agulation was not used in the previously published
surgical series for postoperative management of
therapeutic carotid occlusion.
Fortunately, an excellent alternative to open sur-
gical management of CBS has become available,
consisting at first of various endovascular tech-
niques for occluding major brachiocephalic arteries
[25, 27, 29-36]. Furthermore, within the last several
years, endovascular revascularization techniques
utilizing stent technology also have become more
readily available, providing additional options for
the successful treatment of CBS without sacrifice of
the carotid circulation [37-43].
There are several distinct advantages of endovas-
cular versus open surgical management of carotid
blowout. Although patients managed by endovascu-
lar approach also may be hemodynamically unsta-
ble, there is usually no need to place the patient
under general anesthesia with the additional inher-
ent risks of diminished cerebral perfusion pres-
sure. Because only a relatively small arteriotomy
is used for many types of endovascular operations,
there are generally less difficulties with iatrogenic
hemostasis that frequently complicates a large sur-
gical wound. Since the therapeutic interventions are
directed through endovascular navigation, dissec-
tion through scarred and deformed tissue planes
altered by prior radical neck dissection and irradia-
tion is completely avoided.
As shown by earlier publications by our group [3,
4], precise localization of the pathoetiology of hem-
orrhage can be readily identified in most patients
through meticulous diagnostic angiography per-
formed just prior to endovascular surgery. This
Di„gnc
if Siirgkol M ;'.::.! gem ent o: Cj;'o:id Blowout Synorc
permits specific targeting of the most likely site of
potential or actual bleeding, as well as better selec-
tion of the most appropriate endovascular device
and/or technique. Finally, the added risk of post-
operative thromboembolic stroke after carotid sac-
rifice can be substantially reduced by use of both
intra- operative and postoperative systemic antico-
agulation, which can be done more safely inpatients
undergoing endovascular operations.
Interestingly, the application of these endovas-
cular techniques speciticully lor the management of
carotid rupture is a relatively recent development.
The first reports of successful treatment of CBS
using endovascular therapeutic techniques date
back to the mid-1980s [29, 33, 34]. However, a rigor-
ous evaluation of the specific indications and tech-
nical approaches to this problem did not occur until
1995, when our group at Yale published a prelimi-
nary clinical series on the first 15 patients managed
by an interdisciplinary protocol centered on endo-
vascular surgery [3]. At that time we also recognized
that the various scenarios of carotid rupture actu-
ally manifest in a few discrete and well recognizable
patterns of clinical presentations, which we coined
the "carotid blowout syndrome" [3, 4]. This permit-
ted the creation of a simple classification scheme
that provided a means of rapidly communicating
the nature, severity, and urgency of a given clinical
presentation, which greatly facilitated triage and
therapeutic planning [4]. Our subsequent work and
that of others have shown that CBS can be effectively
managed by a well-coordinated, multidisciplinary
protocol centered on deconstructive endovascular
techniques [3, 4, 21, 29, 35, 36].
Although our results with deconstructive endo-
vascular management of CBS have been overall
significantly better than previous open surgical
series, there is considerable room for improvement,
owing to a combination of acute complications,
technical limitations, and recurrent disease. Prob-
lems such as delayed collateral failure resulting in
stroke, acute intolerance to balloon occlusion of the
internal carotid artery, and recurrent hemorrhages,
remain as significant challenges to still overcome
when utilizing so called deconstructive techniques.
Consequently, we have begun to aggressively pursue
an alternate management strategy using so-called
endovascular reconstructive techniques centered
on stenting with or without adjunctive measures.
Our recently published case series experience with
this approach has been indeed very favorable, and
has now has led us to consider fully adopting this
change in treatment paradigm [43].
This chapter will review some of these issues
and present both diagnostic and therapeutic strat-
egies for managing carotid blowout using modern
endovascular approaches as the centerpiece of a well
coordinated multidisciplinary paradigm.
21.2
Definition
Based upon a combination of our previous review
of the literature and cumulative clinical experience,
our group proposed that the varying presentations
of actual or potential hemorrhage arising from the
carotid circulation can be conveniently classified
within a broad clinical diagnostic scheme termed
the "carotid blowout syndrome" [3, 4]. CBS can be
operationally defined as either an episode of acute
hemorrhage (usually trans-oral or trans-cervical},
or exposure of a portion of the carotid arterial
system (e.g. wound dehiscence, devitalized mus-
flap}, that occurs in a patient who
;ly had undergone a surgical resection of a
neoplasm. Although this classifica-
tion scheme derives mostly from the commonly
encountered clinical scenarios of carotid hemor-
rhage in head and neck cancer patients, it is equally
valid for accidental, intentional, or other iatrogenic
penetrating injuries to the cervical carotid circula-
tion [4].
The clinical spectrum of CBS can be sub-classi-
fied into three distinct groups of affected patients.
This nosologic scheme originally was created out
of a need for enhanced clarity and uniformity in
describing certain clinical scenarios that would
frequently arise, which in turn could permit more
efficient communication and triage between the
clinical services responsible for the care of these
patients. Based upon extensive review of the litera-
ture, these group definitions are equivalent to many
previously described variations of carotid blowout
[3,12,18,29].
The first distinctive type of presentation of CBS
is in patients who develop wound dehiscence from
prior radical neck dissection or flap mobilization,
resulting in a visibly exposed carotid artery. In such
a setting it is well recognized that the exposed artery
will inevitably rupture if it is not promptly covered
with well-vascularized, viable tissue (e.g. free ped-
icle flap, rotated musculocutaneous I lap, etc.). For
such a scenario, although rupture of the carotid
artery has not occurred at this point in time, there
}. C. Chaloupka
is a considerable threat of eventual rupture, leading
to the designation: threatened carotid blowout (or
Group 1 CBS).
A second commonly encountered group of CBS
patients are those who present with a short lived
acute hemorrhage that resolves either spontaneously
or with simple surgical packing. The hemorrhage is
typically either transoral or transcervical through
a surgical wound or fistula. These events may be
episodic, and are considered sentinel hemorrhages
occurring from a ruptured vessel with a pseudoa-
neurysm that intermittently leaks. Because there
is no real wall with supporting structural elements
around the pseudoaneurysm, unconfined rupture
is almost always certain to eventually occur. Such a
scenario maybe described as an impending carotid
blowout (or Group 2 CBS).
The final group of patients with CBS is those
who present with an apoplectic, profuse hemor-
rhage that is not self-limiting and is not well con-
trolled with surgical packing. This presentation
often, but not always is preceded by the above
mentioned sentinel hemorrhage of impending
carotid blowout. In this scenario, there has been
complete rupture of the affected artery and lack
of confinement by the organized hematoma sur-
rounding the associated pseudoaneurysm. These
patients rapidly deteriorate from exsanguination,
unless intensive resuscitation measures and ther-
apeutic occlusion of the ruptured artery is imple-
mented immediately. It is this most catastrophic
scenario that is best designated as acute carotid
blowout (or Group 3 CBS).
21.3
Path o etiology
There are a variety of causes of carotid rupture,
which can be broadly grouped into the following
three categories: traumatic, non-traumatic (related
to "spontaneous" carotid dissection), and those
related to head and neck surgical management
of cervical cancers. Traumatic carotid rupture or
blowout can occur from various penetrating insults
(e.g. ballistic missiles, knives, impalements, etc.) or
blunt trauma (e.g. dissecting aneurysm). Iatrogenic
traumatic injury to the carotid not associated with
head and neck cancer surgery is also an occasional
cause of delayed rupture, typically occurring in the
setting of carotid endarterectomy (CEA). In fact the
original term "carotid blowout" was probably first
applied in the well-known complication of delayed
rupture of a venous graft used for patch angioplasty
after CEA [7].
It has also become increasingly recognized that
non-traumali.: or "spontaneous'' carotid dissection
can occasionally result in significant pseudoaneu-
rysm formation and growth, which arguably may
pose a subsequent risk of a catastrophic, life-threat-
ening hemorrhage. In the past conventional teach-
ing has contended that in the absence of disruption
of the normal fascial planes within the neck (as in
the case of penetrating trauma or surgical inter-
vention), the expanding hematoma that consti-
tutes a pseudoaneurysm should stay well contained
within the carotid sheath, and therefore pose an
unlikely hazard of exsanguination. However, our
group and others have noted rare anecdotal cases
of "breakthrough" hemorrhages occurring in non-
traumatic carotid dissection that resulted in Group
3 CBS. This has in part lead to more of an impetus
toward active intervention when dissecting pseu-
doaneurysms are now diagnosed, although admit-
tedly there is little known about the true natural
history and risk of these lesions to provide strong
evidence-based support of such a management
strategy.
Although recently our group at UIHC has seen
an unexplained rise in traumatic and spontaneous
etiologies of CBS, our overall cumulative experi-
ence has revealed that most cases are an iatrogenic
complication of aggressive multimodality treatment
of malignant cervical neoplasms. It has been previ-
ously hypothesized that there are numerous putative
mechanisms of injury to the carotid artery that ulti-
mately lead to CBS in head and neck cancer patients
[3, 4-6, 8-12, 27]. Both the cellular and extracellu-
lar matrix components of the carotid arterial wall
may be directly damaged from a wide spectrum of
insults commonly encountered with contemporary
head and neck surgical management of cervical car-
cinomas. These include iatrogenic surgical manipu-
lation during functional neck dissections or radical
tumor resections, radiation induced necrosis (from
either an external beam source or intra-operative
brachytherapy), exposure desiccation after break-
down of a reconstructive flap, secondary wound
infections producing fascitis, direct tumor invasion,
and enzymatic degradation horn oiopharyngocuta-
neoin iistulae.
if Siirgkol M ;'.::.! gem ent o: O.;odii Blowout Synoro
21.4
Diagnostic Evaluation
Many patients with CBS present in an unstable con-
dition, which obviously requires emergent triage
and immediate basic resuscitative measures. How-
ever, at some point early in the evaluation of any CBS
patient who is to be considered for possible interven-
tion, a focused, yet detailed history with particular
attention to the specific types and anatomic sites of
previous surgical intervention, is critical for consid-
ering not only where the likely source(s) of bleed-
ing may be located, but also what treatment options
may be most realistically considered. For example,
patients with previous bilateral functional neck dis-
sections and flap reconstructions are more likely
to harbor multi-focal (and unfortunately bilateral}
disease, making deconstructive intervention less
favorable, if not impossible. This is also the case in
patients with a previous history of CBS that required
deconstructive intervention, who return with so-
called recurrent carotid blowout syndrome (rCBS).
Again, consideration of realistic treatment options
will largely depend on whether an internal carotid
artery already has been therapeutically occluded,
and where the suspected source of recurrent bleed-
ing is originating.
A quick and directed otolaryngologic examina-
tion is also an essential preliminary step for evaluat-
ing any patient with CBS. Of particularly paramount
importance is the ability to localize and/or lateralize
the site of bleeding, which will enable a more focused
search for the precise pathoanatomic substrate when
the patient is subsequently studied by catheter angi-
ography. Furthermore, prospective identification of
the most likely potential pathoetiology of the CBS,
such as a flap breakdown with carotid exposure,
presence of a pharyngo- cutaneous fistula and/or
infection, or recurrent tumor can facilitate thera-
peutic decision making when treatment options are
considered.
Often in the setting of Group 2 and 3 CBS, the use
of cross sections I imaging studies are of limited util-
ity, owing to the emergent nature of these presenta-
tions and need for prompt and definitive interven-
tion. However, in patients who are clinically stable or
who present with threatened CBS, CT or MR imag-
ing may serve the dual purpose of not only helping
to elucidate the likely source of active or potential
bleeding, but also assessing open surgical options
for the overall management of the patient's disease.
In our experience, close scrutiny of either contrast
enhanced CT or MRI scans of the neck in the set-
ting of CBS not infrequently shows evidence of one
or more of the following features: pseudoaneurysm
formation, pockets of extravasation, fistulae, tumor
encasement of a large carotid vessel, or prominent
tumor enhancement (secondary to neoangiogenic
hypervascularity). These cross-sectional imaging
studies may be supplemented with three-dimen-
sional reconstruction CT angiography or MR angi-
ography to better define the relevant cervical and
cranial vasculature. These non-invasive imaging
modalities have improved substantially over the last
few years, and are increasing supplanting catheter
angiography for initial diagnostic work up of a vari-
ety of vascular diseases. However, in our experience
we have found that both CTA and MRA have lim-
ited capability in detecting the likely pathoetiologic
sources of bleeding in the setting of CBS, particu-
larly lesions involving the external carotid system.
Therefore, at our institution we do not routinely
utilize either of these modalities in the preoperative
evaluation of CBS.
As in the case lit obtaining a good directed clini-
cal history and physical examination, recognition
of the critical imaging findings relevant to opti-
mal multidisciplinary management can greatly
facilitate the localization ot pathology to target for
intervention. With regards to open surgical plan-
ning, demonstration of the presence and extent
of recurrent neoplasia by cross-sectional imaging
will to a large degree determine whether this is not
only a therapeutic option, but also what endovas-
cular approaches may be preferable to manage the
CBS. For example, a patient who has been previ-
ously "disease-free" or "disease-stable", but devel-
ops a flap breakdown that results in threatened
carotid blowout, may also harbor an unrecognized
primary or nodal recurrence that is amenable to
salvage resection. In such cases (particularly if the
mass is attached to or encasing the carotid artery)
it may be preferable to perform therapeutic occlu-
sion of the artery (providing that the patient tol-
erates balloon test occlusion) above and below the
expected margins of resection in order to simplify
such an operation.
Ultimately, the gold standard for diagnos-
tic evaluation of a patient with CBS is a meticu-
lously performed catheter angiography study of
the head and neck, using modern high resolution
(1024x1024 pixel matrix) and preferably biplane
digital subtraction imaging (DSA) of the cervi-
cal and intracranial carotid circulation. This
requires selective catheterization and injection of
each common carotid, external carotid, and not
infrequently internal carotid artery performed in
at least three different projections. Frequently the
pathology is obvious [4, 27], such as large pseu-
doaneurysm formation, active extravasation, or
fistula formation arising from the ICA, ECA or
CCA (Figs. 21.1-21.3). In some cases the source of
bleeding is not from a ruptured vessel within the
carotid tree, but rather from a recurrent tu
arising from primary or nodal metastatic s
The mechanism of such bleeding may be ei
secondary to invasion and/or erosion tl
oro-pharyngeal or cutaneous anatom:
or from stimulation of tumor neoangiogenesis
resulting in hypervascularity [27].
It must be emphasized, however, that obvious
pathology is not always apparent, requiring one to
maintain a very high index of suspicion when scru-
tinizing the angiographic images. In such cases we
have frequently observed very subtle, and/or non-
specific alterations in endoluminal contour on close
inspection of selective (and occasionally superse-
lective) injection DSA runs that have ultimately
turned out to be the source of bleeding in patients
with Groups 2 and 3 CBS (Fig. 21.4a). The areas that
require the closest scrutiny are around the common
carotid bifurcation, including the external carotid
trunk and its lower branches (e.g. superior thyroid,
facial and lingual branches), and the internal carotid
bulb.
If bleeding is encountered within the lower
neck (particular when involving a tracheostomy
site), bilateral selective arteriography of the sub-
clavian, costocervical, and thyrocervical arter-
ies also must be performed. Angiographic study
of these vessels usually can be closely correlated
with the actual site of bleeding (which should be
marked by a radio-opaque object). In our experi-
ence, the tracheostomy site or underlying distal
margins of a surgical neopharynx are the most
commonly affected structures, which typically
bleed from tumor recurrences, erosions, and radi-
ation-induced necrosis.
The anatomic substrate of potential collat-
eral pathways (particularly involving the circle
of Willis) must also be assessed, which requires
angiographic study of the intracranial circula-
tion from selective carotid and vertebral injec-
tions. Prospective identification of major breaks
within the circle of Willis that result in partial
or complete isolation of the cerebral circulation
[e.g. ipsilateral absent Al segment and posterior
communicating artery (PCoA)], is often enough
to dissuade one from performing a balloon test
Fig.21.1. Angiogram shows a Ia:ge I'seudo.ineurysm of the
common carotid o j lei y iltrgt' ,n rot; }. Narrowing of the inter-
i'.ii] c.U'xid ane:y \:ii:..iil ,ifty-.;s) is a!so piesen;, mos: likely
related to postoperative cicatrization, radiation -induced
changes, or tumor ei
Fig. 21. 2. Left common carotid ane:v iO_"A :■ angiogram shows
a small amount of extravasation from the CCA into the oro-
pharynx (ijjtch-) from a ris-nla That developed after rupture
of a pseud oa neurysm
occlusion in consideration for a deconstructive
intervention. Other anatomic variants, such as a
persistent trigeminal artery are also likely to dis-
courage consideration of a therapeutic occlusion
of the ipsilateral carotid artery.
Diagnosis and Endorascu.ar Surgical Maaagemenl of O.rotid Blowout Syndror
Fig. 21..*. a Ria. - .: C'.:v.;>: n i - ,i ;■'.:■; :■,] .jrlei'y : - l : a l ■■ ■ a : n n l j.'.ows :i iai gc c^rad. -.i^e.i i yj;ii ..■[' ;l;- :a.." -Cc-:vical i ighi nii-ri :".al caood
;:: :ery (ICAi (/dijy .'n/j:/ ,ii/ii;.!. Small concurrent p s en d o p. lieu rysjns of the proximal right ICA tirui'ivti iinon-i) and riglil
externa I carotid artery iKCA! in/H-'" itt'irorj are alio pre ; enl. Ii jiigat .:o ::".::". on caivi.d anerv laieciion after :■ alio on occlusion
of ::g::: o-.'A sj-.ow lire preiidoaneurysm o: the ::g:\: !-_'." A :.iii ran :■ ■= r i . I ■;..[■■. c Angiogram ■ :■■ l -1 : :i j :~. c ... af>r composite pertv.ao.ea.t
balloon occlusion show- embolization ::-i the crucaid systeiv.. A oalloon had oeen oosil loned across i tie origin o: the riglil E'.IA
(<"
*)
21.5
Endovascular Techniques
Over the last decade, dramatic technical and techno-
logical progress in endovascular surgery has greatly
expanded its role in the management of many types
of intracranial and extracranial cerebrovascular
diseases. These advances have been particularly
significant in two categories: (i) new micro-cath-
eterization technologies and (ii) new endovascular
stent systems. Both have yielded devices that are
safer, easier, and ultimately more effective to use.
For now nearly two decades it has been increas-
ingly recognized that the acquired arterial injuries
of CBS are often readily amenable to endovascular
intervention. However, the specific indications and
appropriate selection of techniques and technology
had only recently become better defined in the past
decade [3, 4, 21]. This definition is already undergo-
ing substantial revision and evolution in response to
inherent limitations and complications of various
endovascular approaches [21, 43] and our expanded
technical and technological capability.
Endovascular management of CBS can now be
broadly defined into the two following categories:
"deconstructive" and "reconstructive" approaches.
The former consists of various techniques and tech-
nology used to produce therapeutic occlusion or
"sacrifice" of an affected artery. In contrast, the
latter category consists of various techniques and
technology for eliminating bleeding while preserv-
ing the patency ot an affected carotid artery.
21.5.1
"Deconstructive" Techniques
Therapeutic occlusion of major brachiocephalic
arteries is one of the oldest neuroendovascular thera-
peutic techniques, originally having bet
for the treatment of inoperable aneur
cranial base using simple open ligation or g
clamping (e.g. Seleverstone clamp) of the ca
arteries. Both Serbinenko [30, 31] and Debru:
44] are credited with pioneering the endovas
equivalent of such an approach through thei
of detachable balloons for the treatment of a
types of giant aneurysms (e.g. cavernous segment
in the mid and late 1970s). Today, besides detach-
able balloons, a wide variety of embolic devices
and endovascular techniques may be employed for
deconstructive therapy of CBS. The selection of a
particular device or technique for therapeutic arte-
rial occlusion may be based upon a variety of fac-
tors, including: the specific pathoetiologic lesion
identified on angiography, prevailing cerebrovas-
> of the
rotid
*[32,
J. C. Chaloupka
cular hemodynamics, perceivt
nal carotid artery occlusion
test occlusion (BTO), access ti
for rapid and definitive occlu:
d tolerance to inter-
based upon balloon
the lesion, urgency
lability
and/or comfort level with certain techniques/tech-
Detachable latex (Goldvalve, Nycomed) or sili-
ichable (DSB, Boston Scientific-Target) bal-
e of thee
g rapid o
loons remain as one of the easiest and most reliable
in of a large vessel,
1 carotid arteries,
and therefore in my view continue to be essential
embolic devices tor such applications. These devices
can be readily mounted on various conventional
microcatheters (e.g. Tracker 18 HiFlo Unibody,
Boston Scientific-Target, or Prowler 14 (Cordis Neu-
rovascular, Miami Lakes, FL), and once navigated
into the targeted vasculature, rapidly inflated and
deployed by simple traction detachment (Figs. 21.3,
21.4) As a general rule it is most desirable to place
the first balloon into a fairly distal purchase within
the ICA (typically the petrous segment), owing to
the risk of thromboembolism that may occur from
the creation of a long propagating thrombus in case
of more proximal placement of the balloon within
the cervical carotid [4]. A second important rule
for therapeutic carotid occlusion is to always use a
second so-called "safety" balloon (Figs. 21.3c, 21.4b)
to ensure permanent occlusion, since detachable
balloons on occasion are well know to prematurely
deflate. Optimal placement of the second balloon
will largely depend upon the location of the breach
within the carotid artery, since trapping of the
defect is the effective means of stopping/preventing
further hemorrhage [4]. In some cases, therapeutic
occlusion of the entire carotid system (ICA, CCA,
and ECA origin) is necessary or desirable, such as in
cases of multifocal pseudoaneurysms and fistulaeor
in patients with Group 1 CBS who are candidates for
salvage surgical resection of local recurrent disease.
In such case performance of a so-called composite
carotid occlusion is indicated [4, 21, 27],
Unfortunately, (he use and availability of detach-
able balloons has been steadily on the decline over
the last few years, which just recently were mark-
edly amplified by the abrupt discontinuation of the
only FDA approved detachable balloon in the United
States (DSB; Target-BSC). Currently, it remains
unclear if this device will be reintroduced, which
has created a new impetus in utilizing alternative
techniques and technology.
Many centers have been using various types of
embolic coils (e.g. non-retrievable fibered plati-
num, detachable bare platinum) as an alternative or
adjunct to balloon occlusion of the carotid arteries.
Our group was first to propose using detachable coils
in combination with detachable balloons in cases
where composite carotid occlusion was needed [4].
Although these conventional embolic coils can pro-
duce therapeutic occlusion of large caliber vessels,
such as the common and internal carotid arteries,
there are several intrinsic disadvantages in using
them as the sole embolic agent. These disadvantages
include: (i) lack of precision in deposit ion within the
distal targeted vessel segment; (ii) frequent instabil-
ity of the first "framing coils" in large caliber arter-
a Right common carotid artery angiogram shows a subtle pseudoai
tow), b Lateral radiograph siiows L'.ree .:. era ."liable balloons used i:
distal balloon cove::; [he of. lice o: the oseiuloaneurysm (arrow)
? ! .: its m of the cavernous inter mil carotid artery
permanent balloon occasion of the right ICA.
Di.gnc
ir Surgical Management o: O.;odd Blowout Syndrome
ies that are typi.allv carrying high volumetric blood
flow; (iii) need to use a relatively large number of
coils to achieve occlusion; (iv) increased procedure
time and expense owing to the typically long times
required to achieve arterial occlusion; and (v) pos-
sible increased risk of artery to artery thromboem-
bolism as progressive thrombosis within the coils
occurs when there is still antegrade flow within the
A new detachable platinum coil coated with a
hydrogel polymer recently has been introduced
for intracranial aneurysm therapy (HydroCoil,
Microvention), which our group and others have
found to be also useful for carotid occlusion, at least
in potentially decreasing She number of coils needed
to occlude the targeted artery. Unfortunately theses
coils still suffer from many of the same above-men-
tioned disadvantages. Although no definite proto-
types have been revealed, a few device companies
have indicated some interest in creating more novel
large vessel occlusion devices that may incorporate
certain already existing technologies, such as down-
stream embolic filtering devices, stent grafts, and
hydrogel polymers.
In cases requiring smaller vessel occlusion, such
as pseudoaneurysms or tears to the ECA and bra-
chiocervical branches, both nonretrievable plati-
num microcoils (e.g. Tornado, Cook, Indianapolis,
IN; Vortex, Boston Scientific-Target, Freemont,
CA), and various retrievable/detachable platinum
microcoils (e.g. GDC, Boston Scientific-Target) can
be used. Owing to the enhanced control and safety of
the latter type systems, our group has long switched
over to using them exclusively. Occasionally, our
group has utilized careful injections of small ali-
quots of cyajionavhle-iod-inized oil embolic mix-
tures (Trufill-nBCA, Cordis Neurovascular) to very
effectively obliterate small distal pseudoaneurysms
of the ECA circulation [45] (Fig. 21.5).
Occasionally some cases of CBS are ultimately
found to be the result of hemorrhage from a hyper-
vascular neoplasm (typically in our experience
from transformed squamous cell carcinomas that
have exuberant induction of angiogenesis after mul-
timodality treatment). Endovascular therapeutic
devascularization can be achieved with superselec-
tive transarterial embolization using either con-
ventional embolic agents such as polyvinyl alcohol
(PVA) particles (Contour, ITC/Target Therapeutics/
Boston Scientific, Freemont, CA} or more recently
with the slow polymerizing cyanoacrylate 2-octyl
cyanoacrylate (e.g. Dermabond) [46]. Additionally,
in cases where superselective catheterization of sup-
plying arteries is not feasible, we have successfully
utilized direct puncture tumor embolization with
either absolute alcohol or cyanoacrylate embolic
mixtures [47].
21.5.2
"Reconstructive" Techniques
In lieu of the inherent risks of unilateral therapeutic
ICA occlusion, the unfeasibility of bilateral ther-
apeutic ICA occlusion in most patients who have
already undergone a previous carotid occlusion, and
the high rate of recurrent disease resulting in future
episodes of CBS, there has been a growing impetus
to alternatively consider endovascular repair of the
damaged arterial segment, in an effort to preserve
flow within the vessel. Therefore an alternative
strategy tor (he management of CBS is to reconstruct
the damaged artery through the various mechani-
cal and biological effects of endovascular stents [38,
40-43, 48].
With the increasing use of stent-assisted angio-
plasty for the treatment of extracranial carotid
occlusive disease, it is becoming more widely
acknowledged that such endovascular reconstruc-
tive techniques can be performed with a relatively
low rate of peri-operative cerebral ischemic compli-
cations [42, 49-52]. These ischemic complications,
on average appear to be lower than those for thera-
peutic occlusion of the carotid artery using either
open or endovascular techniques.
There are clearly a few important theoretical
advantages afforded by stent reconstruction of the
carotid artery that may ultimately enhance the over-
all efficacy of endovascular management of CBS.
First and foremost, such techniques are aimed at
preservation of the affected carotid artery, thereby
having the combined effect of broadening applica-
tion of endovascular intervention (for example in
patients who outright fail carotid BTO or possess
an isolated circulation from an incomplete circle
of Willis), and reducing delayed ischemic compli-
cations (which can be both thrombo-embolic and
hemodynamic) Second, the scaffolding and posi-
tive remodeling force induced by placement of one
or more self expanding stents not only maintains
endoluminal patency, but likely reinforces the
mechanical integrity of the arterial wall, which in
the case of CBS has been damaged by the previously
described processes developing as a consequence of
therapy. This ultimately should result in an artery
that is more resistant to future spontaneous rup-
Fig. 21.5a-f. Iatrogenic pseuooanenrysm .:■[' an exle:"ji..i I carol id artery branch af:er '."'-guided biopsy, a Axial noiier.fianced
'".".' image snows 1 lie tip of a .ii 2 -gauge :Ili ib.i needJe within li'.e aiiierior aspect of a sort- i it sue abnormality icniivi/ iinvirj that
Wiii concerning for recurrent sqa anions ceil carcinoma. Histologic analysis showeri only iiiflamma:o:y changes, b.c Two weeks
Liter li'.e patient presents ■.villi artenalizeri epistaxis. l> 'selec:ire righ: external carotid arteriogram, lateral proieciion, shows
mi Id iiTegu.ar.ty •:■: the distal internal maxiilary artery and focai dil.italion of die distill buccal branch idrii'n ). c Peiayed image
from same injection shows ri|j.;g . .;' a 5-::.::'. pser.doaneurysm : inToir:. d-f iindovasculii: surgical management. .1 vhiperseleci.ve
angiogram, lateral oro:ertion afier catheter. zation :■( I he coninion I run I, o: ti'.e descending pa.aiine and bucca. aiinies, slic'ws
filling of the p sen doa neurys in : /,?iyr am' no and adiacenl ex:ravasation i.stiiiill iirrano. e '. -e laved image iiins-ihiracted ) from
same iniection slic'ws persistent tilling of li'.e psetidoaneurysm. I Selective r.giii external carotid arte no gram immediaiely afler
embolization shows complete occlusion of The buccal nranch pseudoaneurysin
iiisii.il Wi'.ii.i^cmenl '.:■:' C.::'o:ii1 ivowoiii Jyiiifo
Cure. Another putative benefit of stent-assisted
reconstruction of an affected carotid artery is the
favorable alteration in flow mechanics that lead to
a reduction in disturbed blood flow and eddy for-
mation that has been linked Co cerebral artery-to-
artery thromboembolism [42,52]. Such favorable
alterations in hemodynamics may translate into a
significant risk reduction of thromboembolic isch-
emic complications.
Consequently, over the last 6 years our group has
progressively moved from a primarily "deconstruc-
Cive" to a primarily "reconstrucCive" paradigm for
the endovascular management of CBS. Thisapproach
first originated in Che mid 1990s at Yale, when we
occasionally encounCered paCients who were noC
candidates for therapeutic carotid occlusion owing
Co ouCright failure of a balloon test occlusion or
angiographic demonstration ot an isolated anCerior
hemispheric circulaCion (i.e. hypoplasia/aplasia of
Che ipsilaCeral Al segment and posterior communi-
cating arCery). During this time our experience with
carotid scenting was starting Co evolve, providing an
opportunity Co try this alternative technique in a few
selected patients [39, 43]. Over time we broadened
inclusion criteria to all patients presenting with CBS
who were at high risk of a stroke from therapeu-
tic carotid occlusion. This included patients with
advance age (>65 years), significant cardiovascu-
lar and/or pulmonary co-morbidities, significant
relative reduction of CBF (> 20%) based on cere-
bral SPECT imaging during BTO, and contralateral
carotid occlusive disease. Within the last 3 years at
UIHC, we have now shifted to attempting a recon-
structive procedure whenever feasible if the affected
arterial segment involves the common or internal
carotid artery, with the expectation that such a shift
in therapeutic strategy could serve the primary
purpose of reducing overall risk of peri-operative
stroke, while at the very least keeping the rates of
immediate and delayed hemorrhagic arrest at the
same level of our previous experience with decon-
sCrucCiveCechniques [43], Arterial injuries involving
Che exCernal carotid tree or rarely branches arising
from the subclavian arteries continue to managed
by deconstructive techniques as was originally con-
ceived in our early experience.
We have successfully utilized a few different tech-
niques of stent-reconstruction for the management
of CBS, which can be broadly classified as follows.
First, in a similar fashion to techniques developed
for the treatment of wide-neck aneurysms of the
intracranial circulation [37,53-56], endovascu-
lar stenting across a pseudoaneurysm can be per-
formed for neck-bridging scaffolding to eventually
support endosaccular embolization [38,39,43,48]
(Figs. 21.6, 21.7). The rationale tor such an approach
originally derived from animal studies of experi-
mentally constructed side-wall aneurysms, which
showed that stent placement alone could result in
sufficient flow diversion and altered recirculation
that ultimately produces thrombosis and neointi-
malization of the aneurysm sac and ostium, respec-
tively [53-55,57]. However, the time required for
aneurysm obliteration can be substantial in such
circumstances, which prompted the idea of trying
to conjointly use thrombogenic coils placed within
the aneurysm after deployment of the stent, in order
to promote rapid thrombotic occlusion [37,55],
This strategy has indeed been used successfully in
an increasing number of clinical cases [39,43,48],
although its application in the treatment of large
pseudoaneurysms is questionable [39]. We have
also experimented with use of alternative embolic
agents, such as liquid adhesives [39], which can be
delivered either by endovascular catheterization or
direct puncture (Fig. 21. 7e) of the pseudoaneurysm.
Although we have had success with such techniques
in a small number of cases, widespread adaptation
has been limited owing to concerns of proper con-
trol and stability of the liquid embolic agent.
The second technical strategy that we have suc-
cessfully employed for management of CBS is the
use of overlapping, self- expanding stents deployed
across the neck of a pseudoaneurysm or along a
weakened segment of the affected artery [43,58],
The major advantage of such a strategy is that the
effective porosity of Che stent cell configuration is
substantially decreased, resulting in a combination
of additional flow diversion away from the aneu-
rysm sac, and markedly reduced bulk flow out of the
aneurysm sac. Such alterations in fluid mechanics
may diminish growth and re-rupture of the pseu-
doaneurysm, as well as promote its thrombotic
occlusion (both spontaneously and iatrogenically
with the assistance of embolic agents). Further-
more, the added relative coverage and scaffolding
afforded by placement of a second stent allows for
better bridging of a pseudoaneurysm neck, which
in turn facilitates more secure placement of embolic
agents (particularly coils). In fact this approach has
overall been so successful that it has now become
essentially a standard strategy in all our cases when
utilizing uncovered stents for endovascular recon-
struction (Fig. 21.6).
For reconstruction of the common carotid or
proximal cervical internal carotid artery, we have
Fig. 21.6a-f. Steni-assisleo
projection) shows two larg
the internal carotid artery
navigation confirms propei
conlroi angiogram after pla
and moderately reduced til
carotid injection 46 h after
gram shows persistence of
with a microcatheter, and
pseudoaneurysm. No
syndrome in whom a large
coiling of pseudoaneurysm. a Pre-rreatmeiii angiogram, right common carotid injection (lateral
e pseudoaneurysms of the right cent r.; on carotid anery :n a patient with Group 2 CBS. Note that
had been previously occluded from an earlier episode -.A 'ZhS. b Control angiogram during stent
positioning of the stent over the diseased segment or trie right common carotid artery, c Delayed
cement of a single Smart Stent. Note i It e markedly oi;v. mi shed f.llmg of the ventral pseudoaneurysm
ling of die dorsal aneurysm. Active bleed .ns; stopped sti'.'itly after ceployment. e-f Right common
first intervention, d The patient developed a seconc episode or '.I.KS 1 days later, in which the angio-
the dorsal aneurysm after sient placement, e The pseudoaneurvsm is. entered through a stent cell
tr anting detachable coil is p.ace.s. f The 'ins. con I :o. anjtioftram s stows cotr.p.ete ooltteral ion o: the
bleeding was subsequemly encotintered. A !-!-vear-olc woman with recurrent carotid blowout
pseudoaneurysm developed
Diagnosis and Endov
if Siirgicjl M ;'.:!.! gem ent o: 0.;e.dd Blowout Syndic
favored using Nitinol self- expanding stents (e.g.
Precise, Cordis tndovascular or Acculink, Guidant),
owing to a combination of factors that include: ease
of access with a long (90-cm) 6-F sheath, high pre-
cision and accuracy of delivery, good conformity
within tapering segments, and relatively high posi-
tive remodeling force after deployment. Our pre-
ferred techniques for carotid stenting are similar to
those used for extracranial atherosclerotic revascu-
larization [42]. For initial access into the carotid cir-
culation, there are two basic techniques commonly
employed. In both cases, a large inner diameter
guiding catheter or sheath must be positioned into
the common carotid (or occasionally the innomi-
nate artery). It has been our experience that place-
ment of a long arterial sheath from a percutaneous
common femoral artery puncture is preferable from
multiple perspectives, including enhanced stability,
ease of coaxial delivery of PTA and stent catheters,
and minimization of the size of arteriotomy. This
technique is performed as follows. A standard 6-F
arterial sheath is inserted into the common femo-
ral artery after single wall percutaneous puncture
and guide wire insertion. A 5-F diagnostic cath-
eter is carefully positioned within the appropriate
great vessel (usually the external carotid artery
origin during internal carotid artery PTA/Stenting),
for subsequent placement of an exchange length
(260 cm) 0.035" or 0.038" (e.g. Amplatz regular or
extra-stiff) wire. The diagnostic catheter and sheath
are carefully removed, while maintaining the distal
purchase of the guide wire. For extracranial stent
cases where a 0.018" SmartStent (O.D. = 2.3 mm) or
Wallstent (O.D. = 2.4 mm) will be deployed, a 7-F,
90 cm Shuttle Sheath (I.D. = 0.10", O.D. = 0.131")
is carefully advanced over the stiff exchange wire,
until a stable position within the parent lesion vessel
(distal common carotid artery) is obtained. We
prefer the final sheath position to be at least 1-2 cm
below the lowest planned stent placement to mini-
mize potential stent deployment difficulty. We also
find that placing a wide arcing curve on the Shuttle
inner dilator and distal sheath, as well as removal of
the intervening rotating hemostatic valve facilitates
navigation of tortuous aortic arches and brachioce-
phalic vessels. Care must be taken to hold both com-
ponents (dilator and sheath) together during initial
advancement. Subsequently, the outer sheath is
independently advanced into position over the dila-
tor and guide wire within the proximal brachioce-
phalic vessels. This latter maneuver is critical, since
the dilator is poorly seen on fluoroscopy (without a
marker band), and therefore may be inadvertently
advanced too far distally into the stenotic lesion if
both components are advanced in tandem. An alter-
native approach that may be employed requires a
coaxial technique utilizing a diagnostic catheter (5-
F, 120-cm) and guide wire (0.035" or 0.038") within
the 90 cm Shuttle sheath, and subsequent staged
advancement of each into the appropriate position.
The diagnostic catheter and its associated curves
may assist in distal navigation, while also minimiz-
ing wire/catheter/sheath transitions. Following sta-
bilization, the sheath is then connected to a large
bore rotating hemostatic valve, and continuous pres-
surized heparinized saline infusion. In some cases,
smaller delivery devices may be utilized, such as
coronary PTCA and stent microcatheters, in which
case a 6- or 7-F thin walled guiding catheter with
larger internal diameters (e.g. Envoy, Guider, Plat-
form) may be placed primarily or over an exchange
guide wire. Appropriate testing of device/catheter
compatibility is recommended before attempting
therapy.
Generally, self-expanding stents (Smart Stent,
Wallstent, Precise stent) are preferred within the
extracranial vessels, especially at the level of the
common carotid bifurcation. The Wallstent has
a greater strut density, but has a tendency to fore-
shorten significantly during deployment, which
makes accurate sizing and placement more dif-
ficult. Although more porous, the Smart Stent
deploys with relative precision and minimal fore-
shortening. The Precise and Acculink stents have
a much lower profile than the Smartstent, allow-
ing facile, less traumatic passage through tortu-
ous anatomy or stenotic segments. Of the two, the
Acculink has somewhat less radial force (positive
remodeling force), which may be an advantage for
treating pseudoaneurysms(i.e. less risk of iatrogenic
rupture). Appropriate measurements of the parent
vessel diameter and length of desired coverage are
required. For the management of CBS, we prefer to
use a stent of 1- to 2-mm greater diameter than the
parent vessel (e.g. a 6-mm ICA would receive a 7- to
8-mm diameter stent). Slight oversizing of the stent
ensures adequate radial tension and approximation
ot the device to the eiuioluminal surface, preventing
migration and early thrombosis. This oversizing also
may promote a delayed mechanical and biological
remodeling of the diseased segment through grad-
ual continued dilatation, and stimulation of various
growth factors and extracellular matrix proteinases
(occurring over days to weeks). Excessive oversiz-
ing of the self-expanding stents should be avoided,
since this may result in vessel wall necrosis, and pro-
Fig. 21.7. a Oblique view or a : ighr common cai'oiiti drier v injection shows ].■ :ge pseud oancuysm isriuigiit ii-noui. Note evi-
dence of prior surgery, including ligation or rhe ex rem.;! carotid artery (cm ivi/ ,l^^. |, ■■. i. b Angiogram afrer deploy mem of an
8x_0-mm Wallsrent across ihe rem in lire carotid arrery shows good disra! runor'r our persistent rilling or" rhe pseud oan.eurysm.
i' Repeat angiogram arlei oeplovnient of a second. overlappi::gi:>!*i'0- mm : IVallstenr shows Aw: tilling of the pseud oan.eurysm.
d I 'elayed ::::age snows siag::aiion ;:if coiirrast material wit in:; the pseud oaneurysm (iji/pi; }. e rluoroscopic spc-r III in shows .:
balloon occlusion carherer within rhe slenrs. wit!; the balloon pai lially mil a red {stt\i:glit iiiio-. i. This j] Jo wee. ioiik ret n. 'grade
llc'W .;if opacilied blood ro rill ihe p send oaneurysm, which was percriraneously punctured with a h-Ci-gauge needle ici/iiyJ
iPi'1'pi! }. f Control angiogram after I wo dnvct-puncture acrylic emoolirraiion^ shoots complete obi i term ion ;;if the pseud oar.cr;-
rvsn: with patency of lire carotid at tery. Subtraction artifact is seen where NBC A was injected ar Ihe site of i upture (di 101; ).
End ova scalar treatm^nr of a head and neck cancer- rehired CF6 oy use or' the self- expanding, covered VV'allgraft stenr
Di.gnc
if Snrgicjl M ;'.::.! gem ent o: O.;odii Blowout Synorc
tracted carotid body stimulation of varying severity
and clinical sequelae. We also prefer to use a stent
5-10 mm longer than the lesion, to ensure adequate
coverage of both the distal and proximal stenotic
segments. Often it is necessary to cross the exter-
nal carotid artery with a stent, owing to extension
of disease into the common carotid bifurcation that
needs revascularization. Our group and others have
observed that this can be done with impunity, since
the ECA in most cases remains patent on follow-up
examinations. In the rare cases when the ECA does
occlude (usually from severe coexistent atheroscle-
rotic disease), patients always remain asymptomatic
secondary to the presence of abundant collaterals.
If a second stent is required, a self-expanding stent
of equal or greater diameter is overlapped with the
primary stent and appropriately deployed. If a self-
expanding stent of a smaller diameter is positioned
within a larger self- expanding stent, the risk of
delayed dilatation and subsequent migration of the
inner stent arises. On occasion, sell-expanding cor-
onary stents (e.g. Radius, Magic Wallstent, Boston
Scientific), balloon expandable coronary stents (e.g.
S7-Medronic AVE, Vision-Guidant), or the recently
FDA approved self-expanding neurovascular stent
(Neuroform, Boston Scientific) may be required for
use in smaller arteries (e.g. distal cervical or skull
base portions of the internal carotid) or in chal-
le using anatomy (e.g. excessive tortuosity or loops).
Great care in proper sizing is requiring preventing
excessive trauma (e.g. oversizing balloon expanding
stents) or stent migration (undersizingboth balloon
expandable and self-expanding stents). On post-
deployment angiography, the stent margins should
approximate the luminal diameter and geometry of
the parent vessels, proximal and distal to the dis-
eased segment. If poor approximation of the stent
margins is observed, post stent dilatation or "flar-
ing" using PTA balloons may be required, although
in the setting of CBS may entail additional risk of
carotid rupture. An alternative strategy is to use tele-
scoping "bridging" stents (typically self-expanding)
to remodel variations in contour and diameter of an
arterial segment [58].
Finally, our group has slowly begun to utilize
covered stents or "stent grafts", as a third alterna-
tive technical strategy for endovascular reconstruc-
tion of CBS (Fig. 21.8). These devices have slowly
evolved over the last several years in which both bal-
loon expandable and more recently, self- expanding
designs have been devised using either native venous
grafts or synthetic materials (e.g. PTFE) sewn into
the inner portion of the metallic stent frame. Such
devices have the major advantage of being more
likely to produce immediate exclusion of an aneu-
rysm from the parent arterial blood flow, which
effectively results in an endoluminal bypass of the
aneurysm. As with bare stent reconstruction for the
management of CBS, proper sizing and precision
of deployment are critical for technical and clini-
cal success. However, unfortunately there remain
significant major disadvantages of covered stents at
this time. In general both balloon expandable and
self-expanding designs are inherently larger in pro-
file for a given targeted vessel diameter, therefore
requiring larger access sheaths and delivery systems.
These larger profile systems can be very difficult, if
not impossible to safely navigate into the cervical
carotid system. The balloon expandable stent grafts
also suffer from problems related to the need for an
open surgical harvesting of a vein graft, increased
danger of pseudoaneurysm/parent artery rupture
from high pressure inflation, poorer flexibility for
navigation into carotid arteries, and less availabil-
ity. Finally, all current stent-graft designs suffer
from inherent increased thrombogenicity, resulting
in increased risk of immediate or delayed in-stent
thrombosis or thromboembolic cerebral ischemia.
Unfortunately, although aggressive ant i- thrombotic
adjunctive therapy using systemic anticoagulation
and anti-platelet drugs diminishes this risk, there
is a commensurate increased risk of perioperative
hemorrhage (often catastrophic) from the CBS.
Despite these limitations our group [43] and
others [59-63] have successfully treated a limited
number of pseudo-aneurysms of the common and
internal carotid arteries. It is anticipated that future
advances in material sciences and engineering will
result in lower profile and more flexible self-expand-
ing stent-graft systems that will pose comparable
technical demands to bare stents. Partially porous
synthetic graft materials also hold the promise of less
acute and subacute thrombogenicity, since they will
be composed or more biologically inert compounds
and may more readily permit neointimalizalion.
21.6
Outcomes
Since 1993, the senior author has managed over 150
CBS events by various endovascular approaches,
likely representing the largest single operator expe-
rience in the world. With this greater than a decade
of ci
:ch ha<
Fig. 21.8a-f. a Initial angiogram jwe-.ils a slump : iinou) ,ii the proximal ex;ernai i! rot id ai tery. b Microc.itheler i mention of
the 5: limp during e nd ova sci: .a r exploration confirms a pse. doaneiiiysni as die source of hemo'ii huge. <: An s?. ?M-mm Wallgraft
stent is positioned ■.villi in the common carotid artery and ICA pi notion, oridgnig _ .i 1 ■=- exit; nal carodd artery origin, d After
deploying die sieni. angiography -hows exclusion 01 die pseucoan.t-ii ysm and normal cahtv: of die parent, stenled ail^iy.
e 1 ngna; subtraction aiigiogiam mask :s shown fo: detail, f ? ho login pli oc die YVallgraf; stent is shown for detail
recognizing the relative strengths and weaknesses of
various endovascular strategies.
Deconstructive techniques founded in sound
basic endovascular principles rapidly proved to be
quite effective in achieving short-term hemorrhagic
arrest in patients with Group 2 and Group 3 CBS,
which approached a rate of over 95% for the first two
case series reported by our group at Yale [3, 4]. In
particular, composite occlusion of the internal and
common carotid segments affected by pseudoaneu-
rysm formation using multiple detachable balloons
and embolic coils immediately proved to be a supe-
rior approach to historical cumulative experience
with open surgical repair of the carotid artery. Peri-
Di„gnc
iiisii.il Milii.igcmeiil o:' C.::'o:ii1 ivowoiii L : yn.:;c
operative major morbidity (neurologic and hemor-
rhagic) and mortality was surprisingly low, initially
in the range of 10% and 2%, respectively. With
increasing experience, the types of deconstructive
techniques applied to the management of CBS nar-
rowed Co mostly combined detachable balloon and
coil embolization of the larger arterial segments (i.e.
composite parent artery occlusion of the common,
internal and external carotid arteries), liquid or coil
embolization of pseudoaneurysms of the external
carotid artery branches, and tumor embolization
using either particulates or liquid adhesives.
Ou [ group's first large cumulative case series [21]
evaluated 46 consecutive patients with a clinical
diagnosis of CBS between 1993 and 1997, who were
referred for a total of 62 events for evaluation and
intervention. Of these patients 43 had undergone
extensive primary and/or salvage radical resec-
tions and had received additional adjuvant therapy/
intervention (e.g. external beam and brachytherapy
irradiation, and chemotherapy) that is believed to
be associated with increased risk of CBS. Again,
overall, the short-term safety and efficacy of endo-
vascular management of CBS remained excellent,
consisting of 100% initial hemorrhagic arrest, 7%
minor neurologic morbidity (0% major neurologic
morbidity) and 2% mortality. However, we discov-
ered a disturbing new problem of additional events
of CBS occurring in previously treated patients that
we coined "recurrent carotid blowout syndrome"
(rCBS). Our group was indeed the first to describe
rCBS, having recognized this previously unde-
scribed complication while reviewing our cumula-
tive first 4 years of experience with endovascular
management of CBS [21]. We specifically defined
rCBS as either a repeat episode of self-limited or
uncontrollable bleeding (i.e. Groups 2 and 3) occur-
ring within 12 h of completed therapy for a previous
episode of CBS, or a newly exposed portion of the
carotid system (Group 1} occurring any time after
completed therapy for a previous episode of CBS.
In this series we found an astonishing 26% rate of
rCBS in treated patients, with an average number of
episodes of almost three per affected patient. Also
interestingly, there was considerable variability
between episodes of rCBS , ranging from 1 day to as
long as 6 years.
Upon reviewing patterns of recurrence in CBS
patients, we observed two readily discernible cat-
egories that could be linked to either proven or pre-
sumptive pathoetiologic mechanisms of recurrent
hemorrhage. The first category could be broadly
defined on the basis of what we hypothesized to
be so-called progressive disease (PD). All patients
within this group developed new events of either
potential or actual hemorrhagic recurrence, attrib-
utable to one or more putative etiologies: (1) surgi-
cal wound dehiscence, (2) free pedicle or mobilized
musculocutaneous flap necrosis, (3) iatrogenic
mechanical vascular injury, (4} radiation induced
arteriopathy, (5) tumor invasion of a major arterial
segment, and (6) recurrent tumor growth and inva-
sion into adjacent mucosal surfaces.
In terms of prognosis and management strategy,
rCBS attributable to PD could be further classi-
fied into bleeding arising from vasculature that is
either ipsilateral or contralateral to the pathoetio-
logic lesion causing the index event (i.e. original CBS
episode). This was the most commonly encountered
type of rCBS, occurring in approximately 65% of
cases. In the PD group 54% had recurrent ipsilateral
disease and the remaining 46% had recurrent con-
tralateral disease.
The second category of rCBS was best defined
simply as events attributable to treatment failures
(TF) (i.e. rCBS attributable to same affected arte-
rial segment or territory that had been previously
treated}. This included recurrent bleeding from a
previously treated arterial pseudoaneurysm, arte-
rial fistula, or tumor neovasculature. Interestingly,
the time course between recurrent events attrib-
utable to TF tended to be relatively short, varying
between 1 and 10 days. In our cumulative series we
found that approximately 32% rCBS could be attrib-
utable to treatment failu res.
Despite our short-term ability to arrest or prevent
hemorrhagic complications in patients presenting
with CBS, the various [>atlioloetiolo;;k" substrates
that originally may have been responsible for the
index event often persist chronically in this patient
population. This persistence of pathoetiologic fac-
tors, which frequently occur bilaterally, would
explain the frequent occurrence of rCBS attributable
to both ipsilateral and contralateral PD. It is inter-
esting to note that within the PD group of patients,
nearly half had an episode of rCBS attributable to
disease occurring contralateral to the index event.
This surprisingly high rate of contralateral events
has the potential of creating serious longitudinal
complications, particularly in situations where a
new pseudoaneurysm develops on the common
and/or internal carotid artery contralateral to a
previously occluded internal carotid artery. In such
cases, therapeutic parent artery occlusion of the
remaining carotid artery carries a very high risk of
catastrophic cerebral ischemia.
J. C Ghalonpka
Although less common than PD, TFs also consti-
tute a major cause of rCBS. This group of patients
develops recurrent events that are directly attribut-
able to repetitive bleeding occurring in the same pre-
viously treated arterial segment or territory. Unlike
the PD group, the time intervals between events
for rCBS attributable to TFs are usually fairly short
(typically in the range of 1-10 days). Several specific
limitations of therapy may explain the associated
high incidence oh CBS attributable to TF. Occasional
technical failures (e.g. inability to cross the ostium
of apseudoaneurysm for endovascular trapping) or
device failures (e.g. premature balloon deflation)
may occur. More commonly, endovascular TF maybe
the result of recurrent tumor hemorrhages that were
previously treated by partial transarterial emboli-
zation with particulates. This technical approach to
tumor devascularization has a higher probability of
short-term failure due to the frequent inability to
achieve ideal superselective microcatheterization of
all arterial pedicles supplying the tumor. This type
of limitation may be overcome with the application
of direct puncture embolization techniques using
either cyanoacrylate or ethanol [27, 47].
The apparent high incidence of recurrent CBS
observed in our patient population raised impor-
tant issues regarding assumptions of durability and
optimization of endovascular therapeutic manage-
ment, and served as the fundamental impetus to try
alternative endovascular management paradigms.
Unfortunately, we are more frequently encounter-
ing situations in which patients may not be candi-
dates for conventional therapeutic ICA occlusion,
owing to one or more of the following factors: (1)
clinical or CBF imaging failure of BTO, (2) sponta-
neous occlusion of the contralateral ICA/CCA sec-
ondary to concurrent occlusive arteriopathy, and
(3) prior contralateral therapeutic ICA occlusion
in rCBS. The option of extracranial to intracranial
bypass in such individuals is usually not favorable
due to the combination of technical limitations in
performing this surgery inpatients with prior radi-
cal neck surgery and irradiation, and the frequent
urgency of presentation [21, 43]. Our group first
described one such patient [39] in whom we initially
attempted to treat a large pseudoaneurysm by endo-
luminal exclusion using overlapping self-expand-
ing stents. Although this was initially successful in
arresting the index event of acute CBS (Group 3),
the patient rebled 24 h later. This prompted us to
attempt an unconventional heroic intervention (i.e.
direct puncture acrylic embolization), which for-
tunately was successful. However, such a technical
approach has potential limitations and risks that
make it unsuitable for a routine primary therapeu-
tic modality [43].
Our center's preliminary experience with selec-
tive use of stent-assisted carotid reconstruction
consisted of 16 CBS events in 12 patients who ful-
filled one or more of the above defined case selec-
tion criteria. These included seven patients with an
incomplete circle of Willis on catheter angiography,
two patients with a contralateral carotid occlusion,
and three patients who failed BTO. Ten patients had
underlying head and neck cancer (83%), whereas
two suffered post-traumatic CBS (17%). Acute hem-
orrhagic arrest was initially achieved in all Group-
2 and -3 patients; however, there were four patients
(33%) who each had one episode of rCBS that neces-
sitated additional endovascular intervention. Fortu-
nately in all cases of rCBS, durable hemostasis was
ultimately achieved after re-treatment. A total of 26
stents were used, in which 22 (85%) of the stents were
uncovered, and the remaining four stents were cov-
ered. There was a 96% technical success rate in plac-
ing the stents; the sole technical failure occurred
when an autologous vein- cove red Palmaz stent
failed to deploy in the carotid artery. In six of the 16
procedures (37.5%), pseudoaneurysm embolization
was also performed using adjuvant acrylic glue or
platinum coils.
One patient developed post- procedural tran-
sient ischemia (TIA), but no permanent neuro-
logical complications occurred in this series. No
deaths were attributable to ERCA although one
death occurred within the 30-day perioperative
period. Specifically, one patient with advanced
HNC (Group III) died from complications of dis-
ease progression (pulmonary embolus) on the
fourth post- operative day. These complication
rates were comparable or lower than those previ-
ously reported for endovascular deconstructive
techniques and stent-assisted carotid angioplasty
of atherosclerotic disease [4, 21, 51].
Unfortunately the rate of rCBS in this series
(33%) was similar to that of our cumulative experi-
ence using deconstructive techniques, highlighting
the continued major shortcoming of endovascu-
lar management of CBS in completely preventing
recurrent hemorrhages. In all cases, rCBS occurred
in the same carotid vasculature that was originally
targeted for reconstruction, thus representing ini-
tial treatment failures as previously defined. Of
interest however, is that these events of rCBS only
occurred when either uncovered stenting or adju-
vant embolization was performed alone. When
Diagnosis and Endov
ir Surgical Management o: '.].'.;■ odd Blowout Syndrome
these techniques were combined together, efficacy-
appeared to be relatively better in preventing future
hemorrhages.
Based upon our experience in the current series, as
well as extensive cumulative experience with endovas-
cular revascularization of carotid occlusive disease in
general [42], we strongly believe that a self-expanding
stent is highly preferable to a balloon-mounted stent
for the treatment of CBS, owing to a variety of techni-
cal and biomechanical factors. Self- expanding stents
(e.g., Waligraft, Wallstent, Precise, SMART) easily
accommodate varying diameters of the carotid tree,
especially at the transition from CCA to ICA, and are
more forgiving when determining the proper diam-
eter size needed. These stents tend to have decreased
porosity compared to balloon mounted stents, which
improves vessel support and promotes pseudoaneu-
rysm thrombosis. They also have superior flexibility
in conforming to tortuous segments of the carotid
anatomy, permitting more facile and less traumatic
deployment. Furthermore, the selection of a self-
expanding stent is preferable to a balloon-mounted
stent owing to the potential for arterial injury result-
ingfrom the requisite high balloon inflation pressures
needed for deployment. This is especially relevant in
the setting of CBS, since the target arterial segment by
definition has been weakened from a variety of pro-
cesses that predispose to CBS. These concerns have
indeed been confirmed recently by Kwok et al. [64],
who presented an example of HNC-related CBS in
which a covered stent (fostent) offered no protection
to high-pressure balloon-stent expansion; extravasa-
tion at both ends of the stent with persistent transoral
hemorrhage required endovascular occlusion of the
common carotid artery [64].
We recently have experienced excellent results with
the currently available VValkratt in, rapid deployment
ofthispolytetrafluoroet hylene -coveredstentproduced
immed iate exclusion of the targeted pseudoaneurysm,
while simultaneously providing reconstructive pres-
ervation of the carotid artery (Fig. 21.8). However, it
must be emphasized that the safe and effective use of
the Wallgraft stent for CBS requires a variety of favor-
able mwvomii: niiii palhophviioloiik lacior^ that were
present in both of our patients. These factors include
common femoral and iliac arterial anatomy that
will permit placement of a large caliber (9- or 10-F)
vascular sheath, simple curvature of the aortic arch,
relatively straight carotid and brachiocephalic arter-
ies, and the lack of coexistent atherosclerotic or post-
radiation stenoses. Therefore, more widespread use of
self- expanding, covered stents for the management of
CBS will not be possible until significant technologi-
cal improvements are realized, such as the creation of
lower profile delivery systems, increased overall flex-
ibility, and enhanced deliverability.
21.7
Future Directions
Endovascular management of CBS has evolved
considerably over the last 15 years, paralleling the
evolution of the specialty as a result of various
technical, technological, and intellectual inno-
vations. Over this period of time we have seen a
paradigm shift emphasis from deconstructive to
reconstructive techniques. It must be stressed,
however, that the full armamentarium of endovas-
cular techniques should alivays be considered when
confronted by each case of CBS, since often the
"less elegant" deconstructive techniques may still
be the best option for definitive management. This
is especially true when dealing with pseudo-aneu-
rysms orfistulae of the external carotid system and
tumor hemorrhages, which really remain prefer-
ably managed by conventional or unconventional
embolization techniques. Unfortunately, extensive,
multi-focal disease of the common and internal
carotid arteries also remains difficult to recon-
struct, and as such may be only amenable to com-
posite parent artery occlusion procedures, using
current techniques and technology.
However, clearly our group and others have shown
the feasibility in managing more cases of CBS with
reconstructive endovascular surgery than what was
originally predicted. As stent-assisted angioplasty
has become increasingly utilized for a variety of
diseases affecting the extracranial carotid system,
major advances in technology and technique have
permitted more facile, safe, and effective placement
of stents into the carotid arteries. Consequently,
techniques described previously such as stent-
assisted coiling and overlapping stent remodeling
are now being routinely used at our center, with
at least equivalent (and possibly superior) clinical
efficacy compared to conventional deconstructive
techniques. We continue to modify and refine these
approaches as increased experience and improved
technology is gained.
As noted earlier, stent-grafts will likely become
more "user-friendly" for management of CBS, and
maybe the better technological solution to the prob-
lems and limitations that remain with current endo-
vascular reconstructive techniques. Inparticular the
promise of lower profile, more flexible and trackable
devices will enable broader application of this tech-
nology. We can also expect further enhancements
in the mechanical and biologic properties of future
graft materials, which will likely translate into better
short- and long-term outcomes.
Finally, it is predicted that modification/manipu-
lation of biological response to implanted stents will
also improve technical and clinical efficacy olencio-
vascular reconstruction of CBS. As drug eluting
technology has already made an enormous impact
on diminishing neointimnl hvperplnslic restenosis
instented coronary arteries, we are likely to see sim-
ilar technology using synthetic pharmaceuticals,
growth factors, cytokines or other biologic agents
that will be applied to bare or covered stents. These
bioactive agents will be utilized to manipulate spe-
cific molecular and/or cellular processes that could
promote certain desirable responses, such as rapid
healing, neointimalization, and enhanced struc-
tural support of the affected artery.
With the advent of these improvements, it is
almost certain that constructive endovascular
approaches, without adjuvant embolization, will
become the treatment of choice for repairing both
the common and internal carotid arteries affected
by CBS. We predict that the use of such devices will
not only substantially diminish the immediate peri-
operative complications, but also decrease the rate
of rCBS attributable to treatment failure that has
a problem with uncovered stents.
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Intervent Radiol 24:253-235
Gene Therapy and Pediatrics
22 Embolotherapy Applications in Gene Therapy
CONTENTS
22.1 Introduction 295
22.1.1 Background 295
22.2 Embolization and Gene Therapy 29fi
22.2.1 Embolization by [nn;s:on o:' Genelii.illy
Altered Cells 296
22.2.2 Embolization as a Prelude to Gene Therapy 298
22.2.3 Embolization as an Adjunct to Gene Therapy 300
22.3 Future Directions for Embolization
and Gene Therapy 300
22.3.1 Cell Transplantation 300
22.3.2 Embolization to Promote Gene Therapy 301
22.3.3 Gene Therapy to Promote Embolization 301
References 301
22.1
Introduction
Gene therapy is an emerging technology that will
likely yield a wide variety of treatments. Initially
gene therapy focused on rare diseases such as inborn
errors of metabolism, but it is increasingly being
applied to common conditions such as cancer and
peripheral vascular disease [4, 12, 13, 22]. Human
gene therapy trials in the United States can be
reviewed online at www.gemcris.od.nih.gov, and
many of these trials include interventional proce-
dures. As summarized in Table 22.1, interventional
procedures include direct arterial injection, direct
injection into tumors, stent placement, and infusion
through a central venous catheter. While Interven-
tional Radiology will certainly play a role in this
field, this chapter will concentrate on the interplay
between embolization and gene therapy.
tfj.MD.PhD
it Professor of Radiology jn: Surgery, Mallinckrodt
Institute of Radioj.'gv mvj W;ish ingtoij University School
of Medicine, 510 S. Kingshighway Blvd. St. Louis, MO 63110,
USA
22.1.1
Background
By its nature, gene therapy is an indirect treatment
method. In most cases, the gene (DNA} must be
transcribed into RNA, the RNA translated into pro-
tein, and it is the protein product that achieves the
desired clinical effect. The transformations from
DNA to RNA and then RNA to protein require access
to the internal machinery of the cell. Delivering the
gene to the cell's interior has been a significant bar-
rier to successful gene therapy. A series of different
strategies have been used; these are summarized in
Table 22.2.
The clinical cond it iond relates what met hod might
be used to deliver the gene to the cell's interior. For
example, correcting an inborn error of metabolism
by gene replacement would ideally entail a single
treatment that confers lifelong production of a pro-
tein. This requirement excludes the brute force and
hybrid strategies, because these only result in short-
term expression of the therapeutic protein. This
requirement also excludes most viral vectors and
leaves only retroviral and adeno-associated viral
vectors. On the other hand, short-term expression
(days to weeks) may he sulticient lor other therapies
such as combating atherosclerosis by angiogenesis
or killing tumor cells. Since a wide variety of vectors
confer short-term expression, choosing a vector then
requires balancing factors such as level of expression
with untoward attributes such as immunogenicity.
22.2
Embolization and Gene Therapy
Three different gene therapy st rategies have employed
embolization (Table 22.3). In the first, cells contain-
ing the desired gene are infused and this method can
lead to embolization since the altered cells are large
enough to occlude vessels. In the second, emboliza-
tion is used to facilitate gene therapy by preparing
techniques used for gene therapy
Selected references
lurea injection inio lesion Inject ,ide:io , v r i:".i I vector con Liming gene wlncl; selectively .-Uls N:-:mvnaitis et al. [14]
Direct injection into tissue Inject adenoviral vector wit!: gene :'oi vasculai growth factor Rajagopalan [16, 17]
Selective intra-arteiul injection Iniecl adenoviral vedor containing gene which Selectively kills Sze [21]
Attach adenoviral vi
Table 22.2. Gene delivery vehicles
Strategy Premise
Brute When cells .ire bathed in Luge None - inject DNA
force amounts of DNA, some DNA directly into tissue
crosses cell's membrane
Elegant Genetically engineered viruse:
provide a highly evolved
method of inserting genetic
material (DNA or RNA) into
Construct agents which mimic Canonic liposome:
the biologic methods used by peptide fusion dor
Easy to produce the
gene in large quantnie-
low immunogenicity
hi':'. ceil I;
long term expression is
possible with selected
Very inefficient means of trait
ferring gene into cells; gene is
expressed for dav-weeks
Large-scale production of
the viral vectors can be dif-
ficult; viruses can induce or b
destroyed by immt
immune response i
systemic illness
Low immunogenicity,
s potential Cell specific
de.iverv
Adapted from Giat
3 [6]
the tissue to receive the gene therapy vector or by
helping target the gene therapy vector to the cells of
interest. Examples are portal vein embolization as
a method of stimulating hepatocyte replication in
the nonembolized segments of the liver and using
Ethiodol embolization to help target a viral gene
therapy vector to hepatocellular carcinomas. In the
third case, gene therapy is used as an adjunct to
embolization. An example is tethering adenoviral
particles to embolization coils.
22.2.1
Embolization by Infusion of Genetically Altered
Cells
The first human gene therapy experiments used
this approach [18]. Cells were collected, genetically
altered and then infused back into the patient. The
advantage of this approach is that the difficult task
of inserting the gene into cells was performed in
the laboratory where conditions could be optimized.
This approach also minimized the possible risks
since the patient was not directly exposed to the
gene therapy vector. In these experiments, circulat-
ing lymphocytes were collected, modified and then
infused. Subsequent studies have used a wide variety
of cell types.
An early therapeutic trial that involved emboli-
zation was a complex protocol that is summarized
in Fig. 22.1. In this protocol, patients with familial
hypercholesteremia caused by mutations in the low
density lipoprotein receptor (LDL receptor) were
treated with the hope of normalizing cholesterol
metabolism [8, 9]. For treatment to be successful,
long term expression of LDL receptors was desired
and this requirement prompted the investigators
to use a retroviral vector because these vectors had
the advantage of inserting the LDL-R gene into the
genome of the harvested hepatocytes (Fig. 22.2).
Other vectors offered only a short-term solution
because genes that are not incorporated into a
cell's chromosomes are lost over a period of days to
weeks.
In this experiment, gene expression was assessed
by several methods. Liver biopsies found hepato-
cytes which expressed the LDL receptor. In addi-
tion, small changes in cholesterol metabolism were
found. However, the clinical effect was negligible
and the investigators concluded that the ex vivo
method was limited by the "low efficiency of genetic
reconstitution".
'-. iiil>. "■ I .:■ liier.i pv Applicai
Table 22.3. Interplay heiween embolization and g^jje theiajiy
Miaiegy
i-X/LLLple
infusion of gene:icaliv altered :::;:::::::;: nan j e 1 1 >
Portal vein eml> 'lizalion siimulales hepaiocy te lepiicadoi;
Elhiodol embolization helps taigei viral vector to tumor
Gene therapy as adjunct to embolization :imho!ize vsing bifu::c:io::a! agent - ;';iii embolization ono pa:: gene liter
Part and parcel
'-. n'.b-.'kz:-, t :.:■[! fac.lnates gene :he:apv
Fig.22.1. Protocol schematic t'.:ir ex vivo hepatic gene therapy.
The lateral segment of ihe patient's live: was removed by a
subcostal incision. ,n\d a Hickman catheter was placed by
sacrificing the inferior mese[i;eric win. The liver specimen
: ■■ !:•!) gmj was :hen per fusee. wi:h co II agenase to release hepa-
tocytes ( -3 billion) which were then divided into 800 culture
dishes. Two days later, a letrovh us containing the sequence for
the LDL receptor was added lc Ihe culture media. The hepa-
tocytes were harvested !_!-] 8 bis I a lei and divided into three
aliquots.Each aliquot w : as infused slowly (J cc/min) back into
the patient's portal circulation using the Hickman catheter.
Adapted from Grossman [8]
j
to
■-I
—
©
©
Fig. 22.2. Schematic for retroviral geiie iheiapv. Retroviral par-
ticles containing RN'A thai encodes the gene of interest are
prepared and added to ihe recipieiv. cells. The retroviral vector
is internalized and the:: releases iis ge::e:ic material into the
cytoplasm. Reverse :ranscnptase c.ses the viral template to
produce a DNA coj.iv of ihe desired gene and :bis gene can then
he integrated into the recipient cell's gen-' ir.e. The integrated
gene then serves as a template fo: lianscription into mRNA
and translation into protein.
Numerous factors limited the efficiency of
genetic reconstitution. First was the number of
cells that were recovered from the liver specimen. A
250-gm liver specimen was resected, and from this
only 3 billion hepatocytes were isolated for culture.
A typical liver contains approximately 100 mil-
lion hepatocytes per milliliter and thus the 250-gm
Id have provided approximately 25 bil-
lion hepatocytes. Second, only 1 billion hepatocytes
were viable, and only 20% of them expressed the
LDL-R after transfection with the retrovirus. Even if
these 400 million hepatocytes expressed the normal
number of LDL receptors, they would have only
the number of receptors typically tottnd in 4 ml of
liver. Since the average liver volume is slightly more
1600 ml [24], even if the methods were improved
100-fold, the result would be a LDL receptor levels
that would still only be 25% of normal. Cholesterol
metabolism is clearly sensitive to the number of LDL
receptors since patients with one half the number of
LDL receptors (heterozygotes for familial hypercho-
lesterolemia) have markedly elevated levels of LDL
cholesterol and develop premature atherosclerosis
pi.
Even if more hepatocytes could be isolated by
either resecting more liver or improving the yield
per gm of resected liver, infusing more of the geneti-
cally altered hepatocytes into the portal vein carries
real risks. Hepatocyte infusion causes occlusions at
the microvascular level and transient increases in
portal venous pressure were observed during the
Ex vivo gene therapy followed by infusion of the
altered cells clearly illustrates the promise and prob-
lems of gene t herapy for inborn errors of metabolism.
While it is difficult to conceive how the transplanta-
tion method might provide more than a few percent
of normal levels for any protein, there are diseases
where restoring low levels of the missing protein
significantly ameliorates the clinical condition. One
such example is hemophilia A where achieving 1%
of normal levels for Factor VIII substantially lowers
the risk of severe hemorrhage [3].
Even with integration of the target gene into a
cell's genome, the durability of the treatment will be
limited by the lifespan of the altered cell unless the
cell divides and passes the desired gene to its prog-
eny. Hence there is interest in genetic manipulation
of stem cells. If the genetically the altered stem cell
has a survival advantage over its endogenous coun-
terparts, this could lead to increasing levels of gene
22.2.2
Embolization as a Prelude to Gene Therapy
The limitations of cell transplantation for hepatic
gene therapy prompted Kathy Ponder, Marshall
Hicks, and this author to study how embolization
might be used as a preparatory step tor gene therapy.
This project stemmed from the fact that retroviral
vectors could integrate genes into the hepatocyte
genome only if the hepatocytes were dividing. In
adult animals, far fewer than 1% of hepatocytes
were replicating under normal conditions. However
based on data from partial hepatic resections and
hepatic embolization, we postulated that occluding
the portal vein branches supplying two thirds of the
liver might be a safe and effective means of stimulat-
ing hepatocyte replication in the remaining third of
the liver (Fig. 22.3).
A series of animal experiments confirmed that
embolizing two thirds of the portal branches stimu-
lated hepatocytes in the spared portion of the liver
to divide [5]. These experiments also determined
the timing and timing and extent of hepatocyte rep-
lication. The embolized liver segments atrophied
and the atrophy was not accompanied by evidence
of hepatocyte lysis. Instead, it was found that hepa-
tocytes underwent apoptosis. Finally, these experi-
ments also demonstrated the feasibility of maintain-
ing ,i catheter in the portal vein tor several davs.
Attempts to build upon this groundwork were
less encouraging. Large doses of the retroviral
vector were prepared and infused into the liver after
embolization using the portal venous catheter. Sub-
sequent blood samples revealed only low levels of
the gene product. Later experiments in a dog model
encountered additional technical issues. Specifically,
it was more difficult to obtain and maintain portal
vein access. Finally a severe immune response was
encountered during retrovirus infusion. These and
other issues prompted Kathy Ponder to stud)' the
feasibility of neonatal hepatic gene therapy. Those
experiments found that a sizable fraction of hepa-
tocytes are dividing in neonates without any added
stimulus. Subsequent work by her group has found
that intravenous infusions led to successful gene
therapy in neonates and the immune response seen
in adult animals was not reproduced [15, 20, 23].
We next hypothesized that portal vein infusion
in neonates might have additional advantages over
intravenous infusion. For these experiments, we
attempted to use the umbilical vein for access and
then select the portal vein. Infusing the vector into
the portal vein might prove more efficient than
intravenous infusion. The approach is summarized
in Fig. 22.4. The small size of the animals and sharp
angles between the umbilical vein and main portal
vein forced us to abandon this model. However, we
still expect that there may be a role for this method
of portal vein in ins ion that might be best studied in
future human trials.
Since embolization alters tissue blood flow,
embolization could potentially be used to facilitate
gene delivery to cells of interest. Embolization could
improve the target to background ratio by altering
blood flow (Table 22.4). Embolization could also
increase the likelihood that the vector will interact
with the individual cells in the target tissue. This
dwell time argument is often cited to explain the
efficacy of chemoembolization.
bb bb BB BSi
BBBB ®& — BB
Fig. 22.3. Portal vein embolization stim-
ulate? hepntocyte replication. Hepato-
cytes and their porta! vein branches are
shown. If the portal vein branch supply-
ing a portion of the liver is occlude,!, the
hepatocytes supplied by that branch
undergo apoptosis. The embolized seg-
ment of the liver atrophies while hepa-
tocytes in nonembolized liver replicate.
'-. iiil>. "■ I .:■ liiei.i pv Apr- 1 ion
i 200-gm pup was delivered
i section, and the umbilical
vein was cannulated with a 20-g Angio-
cath. Diluted contrast was injected and
images recorded in either anteropos-
terior (a) or lateral fb) planes. Vessels
are labeled as follows: umbilical vein
(UV), main portal vein fPV), left portal
vein (LPV), ductus venosus (DV), right
hepatic vein (RHV). a A digital sub-
traction image; b is nonsubtracted.
Attempts to select the portal vein from
the umbilical vein access were hindered
by the angles between the left portal
vein and umbilical vein as well as the
angle between the left portal vein and
Table 11. -I. S l : . i : e t: i e s :oi improving ui^i io background :.
Possible ckmca! example
Flow to
Flow to Target/
Nontarget background
Selectively embolize v<
nontarget tissue
Embolize vessels supplying
lesion and surrounding tisst:
Selectively embolize gastroduodeni'E
nor n; a I tissue, the;; infuse vector via
artery catheter
EmboJize i'.epalic artery orancE using H tar:- ..(.:■.
protect No change Decreased Increased
"Increasing delivery io the target tissue by embolizatio
cause an increase in blooc f.ow to the target tissue.
nsidered because it is unlikely that emboliza
iiBA et al. [19] tested whether embolization
i improve gene delivery Co hepatocellular car-
i. They induced spontaneous hepatocellular
a rats using chemical carcinogens and
performed hepatic artery embolization using Lipi-
odol. It is noteworthy that most animal studies have
used models where tumors are implanted in the liver
and it is a considerable leap of faith to believe that
the blood flow to a tumor 5-21 days after implanta-
tion will accurately simulate the blood flow of pri-
mary or metastatic tumors in humans. Shiba et al.
then tested gene transfer using an adenovirus car-
rying a marker gene. The adenoviral vector could be
mixed with Lipiodol without destroying the vector
because adenovirus lacks a lipid membrane. This
mixture was injected into the hepatic artery and the
efficiency of gene transfer was assessed by staining
for the marker protein and calculating the percent-
age of stained tissue in normal liver, small tumors
and large tumors. In control animals, the adenoviral
vector without Lipiodol was injected into the hepatic
A substantial increase in tumor to background
ratio was found when the adenoviral vector was
coinjected with Lipiodol (Table 22.5). This reflected
an increase in the percentage of tumor cells which
expressed the gene therapy marker as well a
decrease in the percentage of normal hepatocytes
that expressed the marker. The latter is an expected
consequence of embolization. The increase in tumor
cell staining suggests that the dwell time effect more
than overcame the decrease in blood flow caused by
embolization.
The finding that tumor cell staining exceeded
staining in normal liver by approximately sixfold is
remarkable because the available data indicates that
tumors are almost uniformly underperfused [2].
While hepatomas appear hypervascular on angiog-
raphy, at the microscopic level, the tumor vascula-
ture is disorganized. Furthermore, even if a tumor
possessed a well organized microvascular network,
tumor interstitial pressure would reduce perfusion.
The mechanism by which Lipiodol improved the
target to background ratio is uncertain. Prior work
Table 22 5. Marker gene express
on following gene
ransfer
IllieCiion
Tumors <5
Tumors >5 mm
No:' if, a I liver
Vector after iodized oil (n=9)
Vector alone (n=15)
37.4 +/- 6.0
14.0 +/- 3.6
35.6 +/- 9.3
7.0 +/- 1.9
5.7 +/- 1.3
14.4+/- 2.3
The adenoviral vector ti'-r.r.'-Ljiir.t; 7 lie gene :or |'i-ga.aclosidasr was injected .mo The hepatic arlerv o: tumor oea ring ao.imals ei trier
by itself or im mediately following injection o: iociizeo oil. Animals were sacrificed 1 days later and liver sections were .'re oared.
Expression of :iie maraer gerie was dele: milled by staining tor |i-gr lac iosioase. Tire .irea of staining i:i small In mors (-011:11: ), .a rye
tumors i '."■5:1:111) ana normal liver was determined. rLe ,;l .: Irs are exaressir.i as mean pnaemages -■■/- s::i:idara error of the me.in. Nine
animals received the veer:)!" arler iodized 01 a I f animals received rl'.e verier alone. Adapted from Shtba et al. [15]
Fig.22.5. Attaching adenoviral particles
:o embolization coils. Platinum and bio-
degradable coils were coated with colla-
gen to provide a surface for subsequent
attachment of an anti-adenovirus anti-
body. The derivatized coils were then
incubated with the adenoviral vector
which contained tire gene for green fluo-
rescent protein
has shown that injection of Lipiodol into hepatic cyfr
arterial branches results in Lipiodol deposition in to t
both normal liver and hepatic tumors. The initial gene transfer to smooth
deposition in tumors is felt to reflect the large extra- o
cellular spaces within tumors and the different pres-
sures within the arterial and portal systems [10].
were embedded in the thrombus adjacent
. Interestingly, there was no evidence of
icle cells or endothelial
22.2.3
Embolization as an Adjunct to Gene Therapy
22.3
Future Directions for Embolization and
Gene Therapy
Endovascular treatment of aneurysms has focused
on the mechanical aspects of the procedures but the
prevalence of endoleaks and incomplete obliteration
of intracranial aneurysms indicates there is ample
room for improvement. An integrated approach
where the mechanical device also serves as a scaf-
fold for drug delivery has been proposed. In this
scheme, the coils deployed within the aneurysm
might also be coated with a drug which promotes
intimal hyperplasia and the intimal hyperplasia
helps seal the aneurysm neck.
Abrahams et al. [1] recently reported linking an
adenoviral vector to embolization coils. A diagram
of the attachment strategy is shown as Figure 22.5.
These initial experiments tested the feasibility of
this approach both in vitro and in an animal model
of intracranial aneurysms. A marker gene was used
and expression of the marker protein was found in
cells which were in contact with the coil. The animal
experiments detected the marker protein in leuko-
22.3.1
Cell Transplantation
Research in cell based gene therapy represents the
leading edge of how gene therapy and embolization
can overlap. The field remains in its infancy and
the research thus far has focused on the feasibility
of transferring genes into cells and gene expression
after infusion of the altered cells. The nuances of
embolization are largely ignored because most infu-
sions are by an intravenous route and also because
it is desirable to keep these early experiments as
simple as possible. As the technology matures,
there will be increasing interest in embolization
techniques. Catheter directed infusion into specific
tissue beds could be used to improve the therapeutic
window by both by concentrating the cells in the
target tissue and sparing nontarget organs. Most of
these targeted embolizations would be from arte-
rial access but it is also likely that infusion into
I- iiil>. "■ I .:■ rhera pv Applicai
n Gene Therapy
the portal venous system and selected branches of
the pulmonary vasculature will be advantageous in
certain circumstances.
Delivering these cells to the site of interest is only
the first step. The duration ot therapy will be depen-
dent upon the survival of cells following injection.
That survival will depend upon adequate delivery
of nutrients and removal of waste products. This
might seem trivial since the cells will initially reside
in the intravascular space but this location does not
guarantee perfusion especially since the cells them-
selves will likely occlude the vessel in which they
reside. This mechanical occlusion would likely lead
to thrombosis, especially if the transplanted cells
lack the cell surface moieties found on normal endo-
thelial cells. A transplanted cell within a cocoon of
thrombus is unlikely to survive. Ifthis is true, anti-
coagulation either by inhibiting the coagulation
cascade or platelet deposition might improve sur-
vival of the transplanted cells.
22.3.2
Embolization to Promote Gene Therapy
The need to induce hepatocyte replication by portal
vein embolization is fading into the past. Neona-
tal infusions, new vectors and other strategies cir-
cumvent the need for embolization. Further work
is needed to determine if hepatic embolization with
oil based agents can indeed improve target to back-
ground ratios for gene therapy vectors. Ifthis is pos-
sible, it will be critical to establish the mechanisms
responsible so that the technique might be applied
to other organs.
22.3.3
Gene Therapy to Promote Embolization
Gene therapy could be used to improve embolization
outcomes. Interventional Radiology has tradition-
ally concentrated on the mechanical aspects of our
procedures but it is clear that biological coatings
that alter tissue response will become increasingly
important. The same strategy that has been used
to link adenoviral particles to embolization coils
could easily be adapted to link gene therapy vectors
to embolization particles. This technology clearly
illustrates that the key to a successful marriage of
embolization and gene therapy will be understand-
ing both embolization and gene therapy at the cel-
lular and molecular levels.
1. Abrahams JM, Song C, DeFelice S ef a!. (2002) Endo-
vasc.ular mic recoil gene delivery using immobilized
anti-adenovnus antibody for vector tethering, stroke
33:1376-1382
2.Carmeliet P, Jain RK (2000) Angiogenesis in cancer and
other diseases. Nature 407:249-257
S.Chuah MK, Collen D, VandenDriessche T (2004) Clinical
gene transfer studies for hemophilia A. Strain Threimb
Hemost 30:249-256
1. Co 11 in son 1 ■■■, Donnelly H (2004) Therapeutic aitgiogeiies.s
i;i peripheral arterial disease: ojii biotechnology produce
;"ii"; effective co llai era I circiilauoii? Eur 1 Vase End ova sc Surg
28:9-23
S.Duncan IR, Hicks ME, Cai SR et al. (1999) Embolization
'.:' poita! vein branches mcltices hepatocvi^ replication in
swine: a potential step in hepatic gene therapv. Kadiof'gv
210:467-477
i.Giannoukakis N,T:u ccc M : 2003) Cu: rent si. it us and pros-
pec is rot geiiT and cell therapeutics for type : diacetes nir'-
litus. Rev Endocr Metab Disord 4:369-380
7. Goldstein IL, Hobbs HH, Brown MS (1995) Familial hyper-
cholesierolemi.;. In: Scriver Cji.. Fieatidet AL. Sly VVS et al.
(eds) The metabolic -.inc. molecular bases of inherited dis-
eases. McGraw-Hill, New York, pp 1981-2030
3. Grossman M, Raper SE, Kozarsky K et al. (1994) Success-
ful ex vivo gene therapy directed to livt-r in a patient with
familial hypercholesterolemia. Nat Genet 6:335-341
S.Grossman M, Rader DJ, Muller DW et al. (1995) A pilot
study of ex vivo gene therapy for homozygous familial
liypcicholcStefO'Licniia. Nat Med 1 :1 148-1154
i.Kan Z. Wallace S i:ji L J4) Sinusoidal embolization: impact
of iodized oil osi hepatic microcirculation. I Vase Inlerv
Radiol 5:881-886
t.Klugherz BD, Song C, DeFelice S et al. (2002) Gene deliv-
eiv io pig coronary arteries from stents carrying antibody-
tethered adenovirus. l-linr: Gene Ther 13:443-454
2. Manninen l-ll. Makmen K (2002 i Gene therapv lechniqttes
for peripheral arterial disease. Card i ova sc Int^rveni Radiol
25:98-108
l. Mulligan RC (1 993). The basic
ence 260:926-932
4. Nemunaitis J, Ganly I, Khuri F t
tion and oncolysis in p53 mut
an ElB-55kD gene-deleted at
advanced head and neck cancel
Res 60:6359-6366
3. Ponder KP, Melniczek [R, Xu L
neonatal hepatic gene therapy
VII dc
ace of gene therapy ?ci-
(2000) Selective replica-
umorswith ONYX -01 5,
patients with
a phase II trial. Cancer
t al (2002) Therapeutic
. mucopolvsaccharidosis
i.Proc Natl Acad Sli USA 99:13102 i 3 07
ii S, Mohler ER 3rd, l.edcrman :*| <r, al. (2003a)
Regional aiig...'C.eiir- : .s wit ial growth
factor in peripheral arterial ilsusi .i pl'.«c :l randoni-
izr.:.. double-blind, control. t\l .1 . v • • ...U- viral deliv-
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with disabling intermittent dtiu-icjiiin Circulation
108:1933-1938
(.Raiagopalan S, Mohler E 3rd, l.ederman H\ et al. (2003b)
Regional Align: genesis with V.iv n ..: I : .1 ;.-. : ial Growth
Factor (VEGF) in peripheric ■.-.. lenal dadoae. design of the
RAVE trial. Am Heart J 145:1114-1118
i. Rosenberg SA, Aebersold P, Cornetla K el al. (1990) Gene
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cytes modified by retroviral gene transduction. N Engl I
Med 323:570-573
19. Shiba H, Okamoto T, Futagawa Y et al. (2001 ) Efficient and
cancer-selective gene transfer to hepatocellular carcinoma
in a rat using adenovirus vector with iodized oil esters.
Cancer Gene Ther 8:713-718
20. Sleeper MM, Fornasari B, Ellinwood NM et al. (2004) Gene
therapy amelioraies cardiova scu.ar disease in dogs with
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Becher Young invesugaior Award: intraanerial ader
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23 Embolotherapy in Pediatrics
nd Laurent Gar
Introduction 303
Embolotherapy 303
Pre-procedure 303
Indications 303
Consent 304
Prior Laboratory Tests 304
Preparation 304
Anesthesia 304
Setting - Equipment 304
Procedure 305
Fluids 303
Contrast Medium 305
Arterial Access 305
Arterial Spasm During Catheti
Arterial Spasm Following Withdrawal
of the Introducer 305
Embolizing Agents .''05
Post-procedure 306
Main indications in Pediatrics 306
Trauma 306
Pelvic fracture 306
Vascular anomalies 306
Hemangiomas Rem;: lory
to Medical Treatment 308
Kaposiform Hemangioendothelioma 308
Liver Hemangiomas 308
Arteriovenous Malformations 311
Renal Embolization 311
Epistaxis 31]
Hemoptysis 315
Gastrointestinal Bleeding 316
Embolization or Sclerotherapy of Varicoceles
Hvpei splenism 317
Thrombolysis 317
Cfiemoembolization 318
Conclusion 319
References 319
J.Dvbois.MD
Professor of Radiology, Pediatric and Interventional Radi-
ologist, Peportiv.ent of Mec.ic.il imaging, Hopital Ste-lustine,
3175 Cote Ste-Catherine Road, Montreal, Quebec H3T 1C5,
Canada
L. Garel, MD
Professor of Radiology, Pediatric and Interventional Radi-
ologist, Pepartiv.ent of Mec.ical imaging, Hopital Ste-lustine,
3175 Cote Ste-Catherine Road, Montreal, Quebec H3T 1C5,
Canada
23.1
Introduction
Pediatric interventions differ from adult i
tions in several ways: both the setting and the equip-
ment must be adapted to infants and children. The
disease processes and the indications for treatment
are clearly distinct in this age group.
Interventional procedures have been slower to gain
acceptance inpediatrics because physicians were more
conservative, training centers were few in number,
and the equipment not designed for small patients.
Xoivadays, pediatric embolotherapy has become
feasible, thanks to the availability of microcathe-
ters. Such procedures must be performed in tertiary
pediatric centers, because newborns, infants, and
children require special attention in the choice of
general anesthesia versus sedation, control of tem-
perature, fluids, radiation hazards, and dedicated
equipment. These procedures rely upon a team of
trained nurses, radiology technicians, interven-
tional radiologists, and anesthesiologists.
The aim of this chapter is to outline our approach
regarding the environment (setting, sedation,
equipment), and to share our experience in pediatric
endovascular procedures.
23.2
Embolotherapy
23.2.1
Pre-procedure
23.2.1.1
Indications
It is important to ensure the relevance of the proce-
dure. The advantages of embolization by arterial route
over a surgical procedure must be well established. The
potential hazards must be discussed with the attend-
ing staff. A clinician and surgeon must be available as
back-up to face any potential complication.
J. Dubois and L.Garel
23.2.1.2
Consent
23.2.1.5
Anesthesia
Informed consent is obtained from the parent or
guardian. In Quebec (Canada), a child over age 14
has the legal right to sign for him/herself. The pro-
cedure and ill I potential complications must be fully
explained and discussed.
23.2.1.3
Prior Laboratory Tests
Blood tests, including a standard c
up, are mandatory [1].
The majority of simple interventions - biopsy,
venous access, and drainage - are performed under
With the exception of embolotherapy for varico-
celes, the majority of embolotherapies by arterial
route are performed under general anesthesia for
the following reasons: (a) to prevent the child from
moving during a long procedure, (b) to focus fully on
the technique while the patient is monitored by the
anesthesiologist. Besides, embolization with alcohol
carries definite risks, which are well described in the
literature, and for which general anesthesia is man-
datory.
23.2.1.4
Preparation
Patients must be fasting for the appropriate dura-
tion as determined by age and health condition.
No prophylactic antibiotic is administered before
embolotherapy except in children with congenital
heart defects for bacterial endocarditis prophylaxis
[2]. Sedation at the bedside is prescribed by the anes-
thesiologist for anxious children and adolescents.
23.2.1.6
Setting - Equipment
The angiography room must be warm, especially
for newborns and infants. Pediatric anesthesiolo-
gists must have the necessary means to maintain the
child at a constant body temperature: covers, hat,
Bear Hugger, heat lamp, and warming blanket. The
solutions as well as the contrast medium are heated.
Table 23.1. Materials for pediatric angiography and embolotherapy
Introducer sheath: 4Fr (for paiienis weighing less than S kg)
[nlrodt-cer sheath: .~Fr i for paiienis weighing over 8 l-:g)
Catheters - 5Fr and 4Fr i selected .;cco:diiig to I he introducer sheath!:
Celiac trunk catheterization: Hook (Cook! i RIM - second choice)
Superior mesenteric artery: Hook (Cook] (RIM - second choice)
Inferior mesenteric artery: RIM (Cook]
Bronchial artery: Hook (Cook]
Inferior and superi'.'r limbs: Hook (second choice: Tracker, Boston Scientific;
Common carotid: Harwood Nash (Cook)
Microcatheters ! used with the following none t.tpered catheters)
Fast Tracker 18 (Boston Scientific]: Coaxial 5Fr
Renegade 18 (Boston Scientific): Coaxial 5Fr
Excel 14 (Boston Scientific): Coaxial 4Fr
Fast Tracker 10 (Boston Scientific]: Coaxial 4Fr
Terumo guidcwire (the csost often used in otir institution):
Available in different angle shapes :4? :: and W) selected according to arteries angulation.
Transend 14 (Boston Scientific):
The tip of this guidewire has the dislinctive feat tire of being mal. cable and therefore it can be
preshaped before calheterization. For this reason, this guideivire is often used to perform dif-
ficull catheterization.
Mizzen Soft (0.012) (Boston Scientific):
The tip of this guide is smaller than Transend and is sometime useful for distal
'-. nil> "■ I .:■ iiie:.i py .n t-'ed i:i
Pulsed fluoroscopy, low mA, filters,
and coning are mandatory in pediatr:
23.2.2
Procedure
ideocapture, always used: 4-F for under 10 kg and 5-F above.
: practice for Occasionally, when there are specific technical
demands, a 5-F introducer maybe used for children
under 10 kg. Heparin therapy of 50-100 units/kg
is recommended for all infants weighing less than
10 kg, with the exception of those with bleeding
problems [4].
Although partially modified for children (mainly
for shortening their length) the catheters used are
basically the same as those used for adults. The cath-
eterization technique and the embolizing agents are
similar. However, certain details specific to children
must be discussed: fluids, contrast medium, and
equ ipment.
23.2.2.4
Arterial Spasm During Catheterization
The medications used are intraarterial papaverine
(1 mg/kg) or nitroglycerin (2-3 |J.g/kg - which may
be repeated 3 times, maximum 20 Lig/kg), and xylo-
23.2.2.1
Fluids
The fluids administered must be closely monitored
in order to avoid rapid pulmonary overload, partic-
ularly in an infant weighing under 10 kg. It is impor-
tant to inform the anesthesiologist of the quantity
and nature of the fluids that are injected during the
procedure. Specific attention must be given to the
infusion via the introducer, which must be regulated
by a counter to 20 cc/hr. The quantity of rinsing fluid
must be minimised.
23.2.2.2
Contrast Mediu
n of 5 cc/kg must be the rule. It is better
to perform an embolotherapy in several steps than
to exceed the maximum dose of contrast. Aspirating
surplus contrast medium remaining in the catheter
helps to reduce the volume administered. Hydration
should be maintained. Reported rate of minor reac-
tions is 0.9% for non-ionic contrast media [3].
23.2.2.3
Arterial Access
Arterial spasm is frequent in children, especially
when having difficulty with the arterial puncture.
In children, it is preferable to puncture an artery
with a Cathlon rather than a metal needle to lessen
the risk of arterial spasm. A 20-G Cathlon is used
for children weighing less than 10 kg, and an 18-G
Cathlon for children over 10 kg. An introducer is
23.2.2.5
Arterial Spasm Following Withdrawal
of the Introducer
We recommend keeping the limb warm. A nitro
ointment can be applied to the puncture site. Occa-
sionally, a nerve block may be done. The patient
must be on heparin and, it necessary, an intravenous
infusion of rtPA can be used under the supervision
of a hematologist.
Thrombolysis by arterial route is seldom rec-
ommended, particularly for newborns and babies
weighing less than 5 kg, given the risk of damaging
other vessels. Infants have a well-developed collat-
eral network which, in most cases, enables r
larization of the affected limb.
23.2.2.6
Embolizing Agents
The embolizing agents are the same as those used
for adults. The gelatin sponge particles (Surgifoam,
Ethicon, Johnson & Johnson Co., Somerville, New
Jersey) are used for a temporary occlusion, and
the polyvinyl alcohol particles (Contour, Boston
Scientific Corp., Fremont, CA) for a permanent
occlusion. Tissue adhesive: N-butyl-2-cyanoacry-
late (Indermil, Tyco, Norwalk, USA) or enbucrilate
(Histoacryl, Braun, Aesculap) opacified with oily
contrast media and alcohol can also used in pedi-
Specific precautions are needed for alcohol use.
A maximum dose of 1 ml/kg (or 60 ml) per
should never be exceeded [5].
J. Dubois and L.Garel
23.2.3
Post-procedure
As soon as the interventional procedure is over, the
pediatric patient is taken to the recovery room and
then transferred to his/her room. He/she must be
monitored and the catheter entry site checked every
15 minutes for the first 2 hours, and then every 30
minutes for an addition;! I 2 hours. Bed rest for eight
hours is recommended with special attention given
to the limb involved.
23.3
Main Indications in Pediatrics
For pseudoaneurysm accessible by percutaneous
approach, the procedure can be performed under
Doppler guidance (Fig. 23.3a,b). The adequate
needle placement is confirmed by contrast injection.
Thrombostat (Thrombin, Parke-Davis, Scarbor-
ough, On., Canada), 1000 units/cc, is the most com-
monly used agent. We start with an initial bolus of
200 units. If the flow in the pseudoaneurysm is still
present on Doppler ultrasound, we repeat the injec-
tion up to a maximal dose of 1000 units. Since there
is a possible risk of contamination with Thrombo-
stat, we elected to use human thrombin 500 which
is included in a kit available at the blood bank of
our institution (Tissel Kit VH, Baxter, USA). Tissue
adhesive, Gelfoam, or coils can also be used percu-
taneouslv.
23.3.1
Trauma
Organ injuries occur following a blunt or a pen-
etrating trauma, including biopsy. Hematuria,
hemobilia, or intraabdominal bleeding are the rel-
evant clinical symptoms indicating traumatic inju-
ries. Delayed or recurrent hemorrhage is the most
common complication of trauma occurring in 3-8%
of hepatic injuries, 1.5% of liver-spleen injuries, 6%
of liver-spleen and pancreas injuries, and 31% of
isolated pancreas injuries [6]. Pseudoaneurysm with
expanding hematoma and subsequent rupture is the
most serious evolutive complication. CT-scan is able
to identify arterial injuries or fistulae. Angiogra-
phy is indicated in unstable patients with dropping
n patients it
ular lesion
i[7].
: the fum
hemoglobin oi
is questioned
The embolization should be
possible to the injury site to (
tional parenchyma. The emboli
formed by an endovascular route with a coaxial
microcatheter system (Tracker 18, Target Thera-
peutics, Fremont, Ca) to reach the vascular lesion
or by a percutaneous approach under Doppler
ultrasonography guidance. There are several
options regarding the embolic agents: polyvinyl
alcohol particles, isobutyl-2-cyanoacrylate, alco-
hol, and microcoils (Figs. 23.1a-d, 23.2a,b). The
first choice for the occlusion of pseudoaneurysms
is microcoils deposition on both sides of the pseu-
doaneurysm neck [8] followed by in-situ deposi-
tion of tissue adhesive, alcohol, or particles. We
do not use Gelfoam because it is a temporary
occluding agent and it carries the risk of future
23.3.2
Pelvic fracture
Although rare in pediatric patients, severe hem-
orrhage is a significant complication of pelvic
fractures and pelvic crush injuries, and a lead-
ing cause of early mortality. Angiography and
embolization of bleeding vessels have been rec-
ommended for the management of pelvic bleeding
in patients in whom hypotension is unresponsive
to resuscitation and/or surgical exploration [9].
The pelvic vessels are accessed by femoral or axil-
lary approach using Seldinger technique. Once the
extravasation is identified and selectively cannu-
lated, the embolization is performed with Gel-
23.3.3
Vascular anomalies
Mulliken and Glowacki [10] proposed a classifica-
tion that was accepted by the Workshop on Vascular
Anomalies in Rome infune 1996. The vascular anom-
alies are divided into vascular tumors (hemangioma,
hemangioendothelioma, and other vascular tumors)
and vascular malformations. Hemangiomas are the
most frequent tumors in infancy. They are character-
ized by initial rapid growth of endothelial cells and
subsequent slow involution. Vascular malformations
are made of malformed or dysplastic vessels. They
never regress. These vascular malformations are sub-
categorized based on the type of channel abnormal-
ity (arterial, capillary, venous or lymphatic) and flow
rate (hi«h- or Ion- 1 low malformations).
E iiil>. "■ I .:■ rlie:a pv in Pedia
n
.
Fia.2.1.! n-d. Liver trauma in a 15-year-old boy. a CT-sc.an revealed the u;ese;ice of an arleria. pseudoa:ieii:ysni. h Selec;ive
cadieierizjuon of I lie hepaUc a;:ety confirmee [lie pseudoaneiirysiii. c With a coaxial -vs;e::\ (Trac^e:: iic-nc-gade i we overpass
die pse'jcloaneurysiii and occlude the exii hiancb with a coil. The: 1 ., we occlude ihe pseiidoanemvsiii wit/, y.ue fed owed by ihe
occlusion of die afferenl aioery by a coii. d Conl;el a;ig.og:am revealed a compleie occlusion -.A' ti'.e pseudoaneurysm
Fig.23.2a,b. A 10-year-old girl
with severe hematuria post renal
transplant biopsy, a Angiogram
shoi
the
e of a
doaneurysm. b With a coaxial
system, a selective catheteriza-
tion of the pseu doaneurysm
was performed. The occlusion
was performed with a coil
J. Dubois audi. Garel
Fig.23.3a,b. A 10-year-old boy with a p
sonography shows the presence of a ps<
performed with a 22-G Cathlon. 300 im
:udOBneurysm of the femoral artery related
idoaneurysm. b Under u Urn sonography, dire
5 of Thrombostat permit to occlude the pseu
catheterization, a Color ulti
e of the pseud onne'jrysm h
The indications of embolotherapy in vascular
anomalies are: (1} hemangiomas refractory to medi-
cal treatment, (2) hemangioendotheliomas with
Kasabach-Merritt phenomenon, (3) liver heman-
gioma with cardiac failure, and (4) arteriovenous
malformations.
23.3.3.1
Hemangio
s Refractory to Medical Treatment
Ten to 20% of hemangiomas need to be treated
[11]. Medical treatment is the first choice using ste-
roids, interferon, or vincristine. Embolotherapy is
only indicated in cases of ineffective medical treat-
ment. Embolization is mostly performed in cases of
hepatic hemangioma with cardiac failure, heman-
gioendothelioma complicated L>v Kasabach-Merritt
phenomenon, and uncontrolled proliferative hem-
angioma wilii functional ilisorcler (e.g. tongue with
feeding problem).
The embolization provides the control of the
growth of hemangioma in its proliferative phase.
23.3.3.2
Kaposiform Hemangioendothelioma
Mueller [12] and Enjolras [13] reported that
Kasabach-Merritt phenomenon (KMP) is caused
by kaposiform hemangioendothelioma (KHE) or
tufted angioma. The KMP consists of thrombocy-
topenia, microangiopathic hemolytic
localized consumption coagulopathy in association
with rapid evolutive hemangioendothelioma. This
syndrome requires an aggressive treatment, and
carries a mortality rate of 20 to 30%.
Aspirin, dipyridamole, antifibrinolytic agents,
aminocaproic acid, corticosteroid, interferon,
embolization, cyclophosphamide, pentoxifylline,
radiotherapy, and antiplatelet aggregating agents
have been tried with variable success [12-14]. Hepa-
rin has been shown to boost the growth of KHE [12]
and worsens the clinical situation [15, 16].
Embolization aims at reducing the high flow.
Embolization is performed by arterial approach
using polyvinyl alcohol particles or alcohol
(Fig. 23.4a-d).
23.3.3.3
Liver Hemangiomas
The differential diagnosis of hemangioma of the
liver include hepatic angiosarcoma, hepatic epithe-
lioid hemangioendothelioma, or metastatic disease
like neuroblastoma. No treatment is required incase
of asymptomatic hepatic hemangiomas. The main
indications for treatment of hepatic hemangiomas
are congestive heart failure, patients who requires
mechanical ventilatory support, feeding problem,
or Kasabach-Merritt phenomenon. Steroid is the
initial drug. Interferon or vinblastine is reserved
for refractory cases. We believe that embolization
'-. ml>. "■ I .:■ thera pv .n t-'ed i:i
Fia.2.i.-lii-t). A : 3 -year-old boy with rerraclory scroral mid perineal heniangi:: iriii.1o;he.ioma wit;: recc.rreni r-crota I bleed n'.y.
a Selective cath^eri/aiion 01" die perinea I branch from I he inlci na! pudenda! artery through an anastomosis tVoin the common
re mora i arrei y was per to i into. The opaciticadon. c!emonsira:es an impo; '::.:•:. stagiiado:' of contrast m Ihe ".umor. b The embo-
lization was pei formed with Gelfoan'.. c Calfielci nation of [he i'.yy, ;-ga stric a; terv wit:: selective caiheici iz.Uion o:' die perineal
branch from [he interna] pudenda: artery shows a tumor blush, d (Control) angiogram after devasculariziUion of the tumor
with particles
in combination with medical treatment is the best
alternative in symptomatic liver hemangiomas.
Pre-embolization mapping is mandatory, assessing
the potential involvement of intercostal or phrenic
arteries in addition to the hepatic artery and the
portal system [17-19].
Five patterns of angiographic ti tidings had been
described by Kassarjian et al. [20]. Embolic mate-
riel 1 is selected depending on Hie vascular type. Tile
first type, the most classical appearance, is early
filling of abnormal vascular channels, stagnation of
contrast material, and no evidence of a direct shunt-
ing (Fig. 23.5a-h). Type 2 shows high-flow nodules
without direct shunts. Large particles can be used in
type 1 and 2. Type 3 is made of arteriovenous shunts,
type 4 of portovenous shunt, and type 5 of both arte-
riovenous and portovenous shunts.
The embolization is performed by arterial
approach for types 1,2, 3, and 5, and by transhepatic
transvenous approach for portovenous shunts in
type 4. Platinum fiber microcoils are generally safe
in types 3, 4 and 5, and permit the occlusion of the
shunts. Glue (n-butyl-2-cyanoncryhte) is the most
effective material in patients with direct arteriove-
nous and arterioportal shunting arising from mul-
tiple sources [21]. Medical antiangiogenesis drugs
J. Dubois and L.Garel
s.
Fig.2.i."ii -h. A _-:"cntii-oid girl 0:1 steroio neatnim; i v l t :: progressive .'we: hemangioma .-[id reTOn'.g L'roHcr.:, a MK imagiiig
shows a I urge live: iv.Liss iii the right lobe of the liver, b-d The a 01 log ram demons; rates j vascular turn 01 supplied oy "die rig Is I
branch ot' the hep.itic artery with stasmition 0: die conlras; and normal di fining vvm. i!Uis;rnlive of type 1 live: iiemu 11 gi oiy.ii.
c Selective ■."iitiietei izatic:' of the light hep-aide a: :eiv was pel formed. f,g With ,1 coaxiid sysiem, m .duple feeders were catheter-
ize-ci to! I owed by a:' embolizadcn widi pji licles. h i-d-st embolization opacification of the right heoadc ai iery shows a significant
devuscdanzadon of die tumor
should be maintained after embolization
nearly complete regression of the lesions.
Vascular malformations of the liver are
except for the venous malformatic
hemangioma in adults. Most arteriovenous malfor-
mations of the liver are seen in hereditary hemor-
rhagic telangiectasia (Rendu-Weber-Osler) with
hepatic ischemia, congestive heart failure, and
1 portal hypertension. Because of the risk of increas-
ing the hepatic failure, embolization is not recom-
:, mended in diffuse lesions. Liver transplantation is
i indicated in such instances.
Arterioportal fistula in cases of hereditary hem-
orrhagic telangiectasia, Ehlers-Danlos syndrome,
or patients with biliary atresia and cirrhosis can be
treated by embolization.
'-. nib, "■ I .:■ iiie:.i py .n t-'ed i:i
Pure venous malformations are rare and asymp-
tomatic in children. Most of them are seen specifi-
cally in patients with blue rubber bleb nevus syn-
drome which is a familial condition with multiple
venous malformations of the skin, musculoskeletal
23.3.3.4
Arteriovenous Malformations
Arteriovenous malformations (AV.VI) are .in impor-
tant challenge for interventional angiographers.
These his;li I low vascular malformations are abnor-
mal communications between arteries and veins.
We do not understand exactly why some AVMs
respond well to embolization while other AVMs
progress ineluctably despite embolotherapy. That
is the reason why we favor a conservative manage-
ment for quiescent, stable, and non-bleeding AVM
with an annual MRI and cardiac ultrasound. If the
AVM progresses, bleeds, or disfigures, angiography
is essential to provide the road-map necessary for
embolization. The angiographic characteristics of
AVMs are dilatation and lengthening of afferent
arteries, with early opacification of enlarged effer-
ent veins [22]. To destroy the AVM and reduce the
risk of recurrence, a superselective catheterization
with microcatheters is necessary combined with
percutaneous puncture when feasible [23]. The best
agent to destroy the nidus is dehydrated alcohol.
The amount of ethanol needed and the pressure
of injection are evaluated with contrast media test
injections. The maximum dose is 1 ml/kg. Over
1 ml/kg, the elevated serum ethanol levels put the
patients at risk for respiratory depression, cardiac
arrhythmias, seizures, rhabdomyo lysis, and hypo-
glycemia [24]. The ethanol penetrates to the cap-
illary level and totally devitalizes normal tissues.
Balloon occlusion, tourniquets, blood pressure
cuffs inflated above systolic pressure, or a combi-
nation of these can be useful if vascular occlusion
is necessary to induce stasis. Temporary compres-
sion of the venous drainage during the injection
slows the blood flow, but one should relieve the
occlusion slowly to avoid a significant modification
of the pressure within the AVM. Coagulation dis-
turbances have been reported in response to dehy-
drated alcohol thai could increase the risk of bleed-
ing, thrombosis, or hematoma. In these patients, in
which the embolization is followed by surgery, the
use of glue or coils as a substitute for dehydrated
alcohol is recommended [25]; further studies are
needed to evaluate the specific changes that occur
with the dehydrated alcohol. N-bu ty 1-2- cy a noa cry-
late or coils are used for large AVM or to avoid
neuropathy when the AVM is close to nerves.
Many complications are reported particularly
with alcohol embolization, such as pulmonary
embolus, cardiovascular collapse, neuropathy, skin
blisters, radiculopathy, finger numbness, and focal
skin necrosis [23, 24]. Arterial line monitoring and
Swan-Ganz catheters are recommended for large
AVM embolization [24] (Figs. 23.6a-d, 23.7a-d).
AVM can be associated with hereditary hemor-
rhagic telangiectasia (HHT), also known as Osler-
Weber-Rendu syndrome. It is an autosomal domi-
nant inherited disease of the vascular connective
tissue characterized by epistaxis, telangiectasia,
and visceral arteriovenous malformation. The
organs mostly affected are the lungs (Fig. 23.8a-c),
liver, brain, and the gastrointestinal tract. HHT is
difficult to treat and requires a multidisciplinary
approach tor its management.
23.3.4
Renal Embolization
Renal scarring secondary to vesicoureteral reflux
may be the cause of renovascular hypertension.
Renal ablation is an alternative to nephrectomy to
remove to involved kidney. The selective emboliza-
tion should be performed with alcohol to prevent
collateral revascularization. The efficacy is debated
considering that embolization may delay the defini-
tive treatment [26]. Gelfoam and coils are less valu-
able than alcohol because of collateral revascular-
ization (Fig. 23.9a,b).
Selective renal embolization can be useful and
effective in cases of refractory urinoma following
partial nephrectomy or blunt trauma. The goal of
the embolization is to ablate the fragment of renal
parenchyma that is producing and leaking urine
[27]. The embolization is done through selective
catheterization of the vessel adjacent to the leakage.
We recommend the use of particles (polyvinyl alco-
hol) as embolic agent.
23.3.5
Epistaxis
The differential diagnoses of epistaxis in childre
includes trauma, foreign-body impaction, bleedir
diathesis, vascular disorder, vascular anomalii
J. Dubois and L.Garel
Fig.23.6a-d. A 1 7-year-old boy wsth p. rcerjiiiver.o'.LS mo I for ma; ion i AV'V ) o:' die ;hird Jig. I. si ^eleouve o.uneiei izo:ion of die br.i-
ohial a;:ery was peiformeo and showed jii AVM or' :lie ihii\i digit. b,o Perouran.e :■ n s oppiviooo w.is perfo: med. "Juder fhiorosoo.'y,
wilh prior mopping ■.:■:" il'.e AVM from I lie ;i:oeria; side, we pu no; lire oneolly the AVM with o l.'-G hi'.lerrlv needle n two siles.
The joqu I si :i o:'. CiOWS I .: t- :p.:0.roo:io:\ :T L'.e AVM. We m r.Med _ oo ■ ■:' aloohol. d : ■. ■ n L : ■. I .ngi ogre, m oe or lei ;.-l approoo.'. i.".'-ws
;i signir.eant d ev .■ so : ..lonza:i on of [he AVM but o severe orler.ol spas:v.. We mon.iloreo, the ooloration 0110 skin ;empe:oiure. No
arleiial isohen'/o wjs seen: beea : .,se of :lie sigmfieaiiL venous eon.gestion. o noil reseouon was pert"' Milled wrho.ii any icqueior
(reported but rare in Sturge-Weber syndrome), and
nii.i.il hemangioma. The most common indication of
embolotherapy in children presenting with epistaxis
is nasopharyngeal angiofibroma. A benign tumor,
most often seen in the adolescent boy, juvenile
angiofibromas originate from the sphenopalatine
foramen and extend into the paranasal sinuses, the
infratemporal fossa, the middle fossa, and the orbit.
The optimal treatment consists of preoperative
embolization followed by radical surg
CT-scan and MR are essential both for the diagnosis
and the assessment of the tumoral extent.
The arteries supplying juvenile angiofibromas
arise from branches of the external carotid artery
(ECA). The tumor blush is intense and persistent.
There is no arteriovenous shunting within the
lesion. The contralateral ECA should be explored in
all cases that reach the midline. The distal internal
maxillary artery is the first vessel to investigate.
Large tumors are also supplied by other branches
!-_ mbo I o therapy in Pedia
Hg.2.i.7a-ii. A:i i ! -year- old boy widi an arteriovenous malformation i AVM) o: ".he lei": ^h or. Id er. ;i ielec live ca:hcteri/.tlioii oi'
".he posterior circumflex artery from the humeral artery was performed with a Trucker }■?. Angiogram rieiru 'nslrir.ed mukiple
dilated arteries with early venous drainage. l> A Tracker 1 3 was introduced through the Tracker 33 for select ire catheterization
of the arterial feeders. Alcohol was used for embolization. The control angiogram revea.ee. a complete devascdarizauon of the
AVM. c S weeks later a residual AVM was see;: at the control ar;g.ogram. d We used the same coax. a I -vsirm and alcohol tor the
oevasculanzation -:A the residual AVM w.ta a good result
b
i
Hg.2. l .Ba c. A S-vear-cl.i girl with jiendr.-Wener-Osler syndrome. ,i At pulmortarv angiogram, -mall aneurysms din-flirs) are
seen in the left cr.iig. Multiple areas of telangiectasia w.li'. diffuse arteriovenous shuming are seen predomirtanllv in both lower
lobes liinoir/icii:/!. l> On selective injection of the right renal artery, several small aneurysms din-ciu'/icir/i associated with
:elai;g. ectasias [ay >■:■■;. i\ are seen, c After selective imection o: the superior mesenteric artery, a small aneurysm uiiraH and
diffuse area of telangiectasia are demonsl rated in the proximal jejunum
J. Dubois and L.Garel
Fig. 2 3.9a, b. Akohol e:-LL"iojzo;io:i :■( o nop hio kidney :oi rct":oo:o:y hvpenei'.s lor., a Se.eoiiv- ooihetensni of .e:'l je:".;il 0Ke:y.
h Reno] .uteiy opLiiilkjlion of:ei okohol embolization shows o complete devosaLiinzation of [lie kidney. NoiT.iuizoiio: 1 . o:"
blood pressure was noted
such as the accessory meningeal, the ascending revascularization) is usually performed with par-
phai vngeal, and the ascending palatine arteries. In tides or tissue adhesive (Fig. 23. 10a, b). When the
case of intracranial tumor extension, the hemody- tumor has invaded the cavernous sinus, the pitu-
namks (anastomoses) between the internal max- itary fossa, the suprasellar area, or the intracranial
illarv system and the ipsilateral internal carotid intradural area, permanent preoperative balloon
artery must be analyzed carefully. Distal emboli- occlusion of the internal carotid artery could be
zation (proximal occlusion would result in tumor helpful [28, 29].
flg.l ■-lOo.ti. I ::■■■.-.' i.- pli.i! ■:.)!-. . .::;g;oii : o . I v r .n ...-,|,- ; .y. ;-!-■ pei ot.ve =■ j j"i L" ■ :■ . i ^ o : l ■; ■ n wi:l'. portholes of trie oi Le-
na I bronohrs oi f I he inlemol maxillary artery, a s elective ex lei no I corolid angiogrom shows o vascular tumor le-ci by multiple
branches :■( ijie in;ernul moxillory orlerv. I> A fie: mukiple s^c live caihelc: izalion \vi:h .: cooxia! system i Tracker o- ond Trackei
18), embolization wos penormed kilIi poi ucies. Pos'.embokzoiioii -.i n g i i:-gi :.:•:. shows sigmficoiit de vascularization
'-. nil>. "■ I .:■ theta pv in t-'ed i:i
23.3.5
Hemoptysis
Most patients who may benefit from bronchial artery
embolization are teenagers with cystic fibrosis (CF)
and major hemoptysis. The hazards of general anes-
thesia with positive pressure ventilation inCF patients
have been addressed recently in the literature. A
fatal pulmonary hemorrhage during induction was
reported by Mcdougal and Sherrington [30]. The
technique is well established: femoral artery access,
5-F catheter, precise vascular mapping, coaxial tech-
nique with Tracker 18 catheters, secure catheter
placement prior to performing embolization, and use
of polyvinyl alcohol particles (size: 355-500 microns
or 500-710 microns if microfistulas are observed)
(Fig. 23.11a-d). Coil embolization or surgical ligation
of bronchial arteries should be avoided because they
hinder subsequent catheterization of the proximally
occluded vessel. Careful attention should be paid
for the identification of spinal arteries arising from
the bronchial or intercostal arteries. The localizing
value of emergency bronchoscopy or multidetector
CT scanning prior to embolization remains to be
evaluated.
Bronchial artery embolization in CF patients is
very effective immediately and on short-term basis.
Many patients will require repeated embolizations
during the follow-up [31], 1 Vspite the reported severe
complications of bronchial artery embolization, the
procedure has proved to be safe if performed by
experienced angiographers.
Fig. 2.V I ] a-il. Hemolysis in .'. i 7-year-old boy wiih -."y~:ii" flnrosis. a Selective catheterization, o: tite light crouch i a I ;iririy with
a 5-F hook catheter shows dilated anci tortuous arteries in the superior .'.ad middle pulnioaaiv lobes, b With a coaxial system
:. kvnegiv.e 1 Pi, an embolizai.oi": was perfoimed with particles 1 Contour 500-733 microns). Postembol.z.tiion angiogram shows
olevasculaf.zi'.tion ct trie bleed, ng site, c Seleot ive c.'.theteriziition. o'i Ihe broncho-intercostal Ir.inL \iulliple ciliated and tortu-
ous arter.es are seen, d selective catheterization wiih tiie same coaxial system. Embolization was peiformeo with pi'.rucles.
i-rsiemholiziU.on angiogram shows complete- devaso.ilarization
J. Dubois and L.Garel
23.3.6
Gastrointestinal Bleeding
In children, localized gastrointestinal bleeding is
usually secondary to duodenal ulcer and less fre-
quently to gastric ulcer, Meckel's diverticulum, and
vascular malformations. Diffuse bleeding can occur
in vasculitis and coagulopathy.
Gastrointestinal vascular anomalies are often
associated with known syndromes such as Klippel-
Trenaunay, Rendu- Osier-Weber, blue rubber bleb
nevus, and Proteus syndromes.
In our experience, venous malformations are the
more common vascular anomaly encountered in
cases of bleeding (Fig. 23.12a,b).
In children with gastrointestinal arteriovenous
malformations, the angiographic examination con-
firms the diagnosis and the extent of the AVMs.
Embolization is usually not recommended in small
bowel and colonic lesions because of the risk of
necrosis [32, 33]. Embolotherapy is sometimes con-
sidered preoperatively to lower the risk of operative
bleeding.
23.3.7
Embolization or Sclerotherapy of Varicoceles
Varicoceles are present in 15%-20% of preadoles-
cents and adolescents. The treatment of varicoceles
in this age group is controversial. The treatment
can be surgical, endoscopic or radiological (sclero-
therapy or embolization of the internal spermatic
vein). Most of the varicoceles are seen on the left
side. Bahren et al. [34] described five types of left
varicoceles according to the anatomy of the internal
spermatic vein (ISV).
Irrespective of the type of varicocele, the sclero-
therapy procedure is the same. Our technical pro-
tocol for percutaneous endovascular occlusion
of the ISV is as follows: IV sedation by Ketamine/
Midazolam, femoral vein approach, 7-F Cobra
catheter with coaxial 3-F or Tracker 18 for distal
sclerotherapy by sodium tetradecyl sulfate (STS)
followed by more proximal coil occlusion, bed-rest
for 4 hours, and discharge 6 hours post-procedure
(Fig. 23.13a,b). Results are assessed by the referring
surgeon 2 months later.
In our series, we have found a high incidence (-[■[%)
of anatomical variants in the pediatric population.
Technical difficulties of retrograde sclerotherapy
were seen in type IVb. collaterals from segmental
renal veins to the internal spermatic vein with a com-
pete nt ostial valve (12% of our cases, failure rate 50%)
and in type V, double renal veins (14% of our cases,
failure rate 33%). Our overall results (failure rate 10%)
are comparable to the recently reported pediatric
series [35, 36], in the radiological and surgical litera-
ture. The issue of radiation related to interventional
procedure has been addressed in the literature. If the
if the light colli: .iiiriy shows dyspljs
Fig.23.13a,b A 12-year-old boy with left varicocele, a Selecrive catheterization of the left spermatic v
coaxial 3-F catheters. I> iniection of 4 cc of sodium r e r j" .1 J e ■." y J sulfate- with proximal coil occlusion
t-f cobra and a
usual principles of radioprotection a
gonad-dose (0.01 mSv) is negligible.
23.3.8
Hypersplenism
The causes of Hypersplenism in children are cirrhosis
secondary to cystic fibrosis or biliary atresia, portal
vein thrombosis, thalassemia, and idiopathic throm-
bocytopenic purpura. Hypersplenism is treated by
surgical resection with subsequent increased risk of
infection in the pediatric age group.
Partial splenic embolization is an alternative to
splenectomy. Preprocedural and postprocedural
antibiotic prophylaxis is recommended. Under gen-
eral anesthesia, the embolization is performed with
a femoral 5-F catheter. The catheter is advanced
through the femoral artery to the mid splenic artery.
Subsequent catheterization into the intrasplenic
arterial branches is performed either with the 5-F
catheter or if necessary, coaxially with a microcath-
eter. The embolization is done with an iniection
of polyvinyl alcohol particles and antibiotic solu-
tion containing 0.2 mg of ampicillin (Fig. 23.14a,b).
Splenic embolization is monitored angiographically.
The procedure is completed after approximately
70% of the splenic parenchyma isdevascularized [6].
Aggressive pain control is needed for 7-10 days post-
procedure. In children, Harned [37] demonstrated
that 30%-40% embolization of splenic blood flow
is enough to improve the platelet count and white
blood cells with a shorter hospitalization, faster
recovery, and fewer complications. Complications
of splenic embolization include fever, leucocytosis,
pain, pleural effusion, splenic abscess, and peri-
tonitis. The long-term results after partial splenic
embolization have not been well established [38].
Up to now, partial splenic embolization as treat-
ment of Hypersplenism in children has not gained
wide acceptance in western countries.
23.3.9
Thrombolysis
Experience with thrombolysis in children i
ited but the need for this procedure I
because of the need to treat complications of cardiac
catheterization and systemic arterial intervention.
Agents used include urokinase and rtPA. Effective
dose schedules for children have been extrapolated
from adult studies. Coagulation and fibrinolysis are
probably different in pediat 1 ics, particularly in neo-
nates. Plasminogen levels are known to be low in
neonates, and it has been proposed that plasmino-
gen or fresh plasma be given to enhance fibrino-
lytic therapy. Most centers favor rTPA, and this may
be locally delivered via a selective catheter. Local
low-dose therapy is unlikely to produce systemic
J. Dubois and L.Garel
Fig.23.14a,b.A /-yeor-old hoy with spheno.cytosk on..: ■".yi'eisn.eaism. a Selei":iv=? L.iihcici'iz.ii.oij •:■< ti'.e -^leen shows die j
div ;y, i ;gr. '.;•.; of the sn.een. b Pcs:.fmbol.i.ai::oi .1 ngii:-gr;i:r. will', i.'.e lesiduol n or en c by ma
changes in coagulation, whereas systemic therapy
will and therefore has greater risk and more contra-
indications. In all systemic therapies, the fibrinogen
level, thrombin time, prothrombin time, and acti-
vated partial thromboplastin time are monitored at
regular intervals, and the children are observed in
an intensive care unit or neonatal nursery. Systemic
therapy with heparin is recommended for indwell-
ing catheters, but its role in the neonate is uncertain.
The trend in thrombolytic therapy is toward higher-
dose, shorter-duration treatment given locally,
which often produces rapid clearing of thrombus.
Failures may be related to delays in implementing
therapy, going to maturation of the thrombus.
The most common lesion treated in the authors'
center is femoral artery thrombosis complicating
catheterization, especially for balloon angioplasty
of the aortic arch or aortic valve. These procedures
require the insertion of a large balloon, which is
currently mounted on large shafts. Initially a local
low-dose approach from the opposite groin was pre-
ferred, but now systemic therapy is frequently used
if there are no contraindications. Local low-dose
thrombolysis is used for thrombosis of Blalock-
Taussig shunts, dialysis fistula, pulmonary artery
thrombosis, iliofemoral thrombophlebitis, aortic
thrombosis in neonates, and brachial artery occlu-
sion after supracondylar fracture.
Bleeding is the most serious complication of
thrombolytic therapy. Cerebral hemorrhage is a
concern in the neonate, and in this age group the
authors elect local low-dose treatment. Bleeding
from recent surgical sites is also a well-known com-
plication of thrombolysis.
23.3.10
Chemoembolization
We have no personal experience of chemoembolization
and the pediatric literature on the topic is scarce.
According to the International Society of Pediat-
ric Oncology and the Pediatric Oncology Group, the
standard therapeutic protocol for childhood primary
malignant tumors of the liver is based on the associa-
tion of systemic chemotherapy and surgery [39-44].
Such an approach has improved signilicantly the out-
come of hepatoblastomas, especially when the tumor
is unresectable at presentation. Some case reports
and a few series have outlined the interest of preoper-
ative hepatic artery int 11 sion ot eisplat in and/or doxo-
rubicin and of TACE (transcatheter arterial chemo-
embolization) in advanced hepatoblastomas [45-51].
According to these reports, the results were more than
encouraging, with a much lower toxicity than con-
ventional systemic chemotherapy. To the best of our
knowledge, however, no study has demonstrated the
superiority of preoperative TACE over preoperative
systemic chemotherapy in increasing the resectabil-
ity of initially inoperable hepatoblastomas. Besides
hepatoblastomas, TACE has been reported also in
pediatric cases ot hepatocarcmoma [?2] and even
hepatic metastases [53]. According to the proponents
of the technique, TACE appears feasible in children
and can be performed in cases of unresectable tumor
confined to the liver, when the portal vein is patent,
and in the absence of biliary obstruction.
Inadvertent pulmonary lipiodol embolism during
TACE has been reported in adults [54] and children
[55].
E iiil>. "■ I .:■ rhera pv in [-' e J i ;i
Transarterial catheter chemotherapy and/or
rinb''! i.-'.ii lion in the management ot advanced
hepatic malignancies is still a work in progress and
has not been endorsed by the international pediat-
ric oncologic societies. On the other hand, the future
development of gene therapy in children delivered
through a vascular route can already be antici-
23.4
Conclusion
Embolotherapy of small vessels in small patients
needs well- trained pediatric radiologists and a ded-
icated environment. Networking between the few
centers performing such procedures in children is
paramount for continuously optimizing both their
indications and their techniques, and for assessing
their effectiveness.
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Subject Index
-aorta 103
itbsolute
-alcohol 11,192
-ethanol 169,204,205
acalculous cholecystitis 185
accessory 144
- meningeal artery 239, 259
- renal artery 113
- rid'.l hepatic artery 151
active bleeding 103
acute pancreatitis IH5
adenoviral vector 251
aetmtisclerol 2H
airv. :v
compromise 35
ma::ajjerr.cnl
equipment iH
|v-;-*-,i.:-.i:pi r/'irapy for intubjt
alar artery 259
ale: ■:-..:. .;.-.. HI
allopurinol IBfl
;;!p!i:i-fe:. /protein i 2 9
i'.iiiiramy 52
ancillary vessel 152
- arterial wall 100
- configuration 101
-fusiform 100
- mycotic 100
- pseudoaneurvsin 100
-rupture 109,114
-saccular 100
- true aneurysm 100
I'.IlgioiTl.itOllS
- polyps 264
- "vascularization 192
angiomyolipoma 101,113,202,210
- spasm 30.i
angn
225
angioneogenesis 225
anosmia 247
- cerebral artery 235
-EPX 257
- septal artery 259
amiangiogenesis agent 222
anticoagulation 123
apoptosis 164
.j failure i
- fistula (AVF) 3,11,12,64,6
- ma [formation 3,311,313
- clinical stages 8
- - iTongestivi
--CT 9
- MR imaging 9
- percutaneous manag
- - soft tissue mann S
- shunting 134
a tli ero sclera sis 101
autopsy 113
autosomal dominant dis-
AVE 285
AVF, Si
avitene 242
AVM 9,243,311
bacteria! endocarditis.
balloon 273
- balloon- mounter siei
- catheter 241
-occlusion 273
- tamponade 87
bare metal stent 104
bevacizumab 222
biliary
-atresia 317
- indocyanine green
biochemical pump 224
biopsy 90
birthmark 3
bleeding diathesis 311
blue rubber tieb nervus
bone
- healing 196
- embolization 191
- - estimated blood loss 193
- - obliteration of tumor blush 193, 195
- - post-emboliz.ttion syndrome 196
bowel
- ischemia 112
-preparation 135
breast 149
-perfusion 82
3-bromopyruvate (3-BrPa]
222
colorectal carcinoma 149
bronchial artery ernbolizaii
on 315
common iliac 71
Budd-Chiari disease 164
complication 212
congestive heart failure 202
connective tissue disorder 111
C
contour SE 205
c-.iucirr ai'.giogenesis 132, 1
44
com ra s 1- in c! : .; ceo nephropathy 210
capecitabine 150
corpuscular element 21 1
capillary
corticosteroid 5,245
- hemangioma 264
- therapy 196
-malformation 16
covered stent 285
carcinoid 131,139,169
cranial nerve 236,267
- liver metastases 182
craniofacial tumor 254
-syndrome 178
critical FRL 171
-tumor 177
cryotherapy 158,201
- - metastatic 133
CV'l. see lower-extremity chronic ver
care! j ;;c arrhythmia 1 1>
cyano; cry late 167, 168, 180
caroticotympanic artery 236
cystic
caroticovertebral anastomose 239
-fibrosis 315,317
carotid
- media! degeneration 1 11
-blowout 244,271
cytokine 164,170
-dissection 274
cytolysis 170
- occlusion 272
cy to reductive procedure 178
-rupture 271
- tumor 253
causative agent 51
D
cauterization 258
debulking ::ip":-rectomy 201
CCC, see c hula *:niin:dl Jar
carcinoma
iliTiyilrstt-d .ilc.ih.ol 311
celiacaxis 133
d:':.l,' il 1.
cell cycle enzyme 222
balloon 114,241,277
cell transplant n:n ,10 n
r>ari: plaii::_m coil 244
chemical i ir^iru^t:-: 293
-latex 273
chemodeclnma 251
-platinum coil 279
chemotaclic factor ! 32
diabetes mellitus 172
chemothi-apy : .1"
diaphragmatic artery 132
- mixture
direct thrombin injection 105
- - admission orders 136
cisseminated intravascular coaguiaii
--cisplatin 134
cislal internal I'.iaxklaiy ,u lei v _?■
— complications 136
oiverdculitis III
- - doxorubicin 134
dominant autosomal disease 266
— hydrochloride 134
dorsal
— lipiodol 134
-aorta 236
— materials 135
- '.';~ii:hal:n;c artery 235
— mitomycin C 134
doxorubicin 180,222
cholaiigioceliular carcinoid
a (CCC] 129
- doxorubicin-eluting bead 228
chronic idiopathic thrombi.
■cvv-penic purpura 215
drug-carrier 224
cicatrization phase 125
drug-eluting 226
circle of Willis 276
drug-loaded embolic agent 228
circulatory shock 38
ouodenal ulceration 100
cirrhosis 21 1
duplex ultrasound 70
cisplatin 222
DVT 124
- cisplatin-londe-d polyid.l-iacddei microsphere 228
classification of Pisch 250
clinical toxicity 157
E
clival artery 238
ecchymosis 123
CNS depression 16
Ehlers-Danlos syndrome 101,310
coagulopathy 263
electrolytic detachment 114
hmboGold microsphere 205
embolic agent 192
-deposition 106
-embolization 107
embolization
collateral
- equipment list 84
- pathway 82
- of the superior gluteal artery 66
embosphere 93,130,134,192
- microsphere 226
enbucrilate 305
encapsulated microorganism 211
endoglin 266
end organ supply 1 14
endothelium 204
endovenous thermal ablation
- clinical success 123
■n rates 124
- e\'Lnephrii
123
iS thermal injury 122
-laser 121
-RP ablation 121
venospasm 122
HNTbleeding 257,269
en terobihary anastomosis 185
or'eri chromaffin cell 177
■ y ] 77
o;.vdu:ai m. sthesia 213
eprubicin 222
episodic KPX 266
ep:staxis 257,311
epitbelioid angiomyolipoma 202
:..-.' < 264
e:-anl tnn :lization 193
erythrocyte 204
poh/amine 164
esthesioneuroblastoma 248
estimated blood loss 192,209
e:han:il 2H.30,203
ablation 113
eti'.anolainme oleate 2S
ethibloc 29-31
ethiodol 223,225
ethyl alcohol 243
eustachian tube 258
extern.;! carotid artery 23?, 236,264
extracranial meningioma 248
exti ahepalic
72
familial hypercholesteremia 296
fatal toxicity 157
IS FDG-PET 159
femoral artery 73
- - percutaneous ernbolizaiio
- - postcatheterizalion 69
- surgery 70
- techniques 71
- - thrombin injection 71
- transcatheter 71
- - ultrasound-guided compr
- pse-;doaneurysm 84
fibromuscular dysplasia 101
fibrosis 170
i-isch Classification 1-1%
flap breakdown 275
floxuridine(FUDR) 149
fluoro-fade 191
fluorouracil (5-FU) 158
flush syndrome 169
foam 30,31
fracture of the pubic ramus 63
frequent spontaneous EPX 266
fresh frozen plasma I 91
FRL, see future remnant liver
5-FU, see fluorouracil
FUDR.seefloxuridine
future remnant liver (FRL) 163
■"""TV -galactosyl serum albumin 172
gangrenous cholecystitis 185
gastrin 181
gastrinoma 177
gastroduodenal
-artery 103,151,185
-necrosis 134
gastroepiploic 212
gastrointestinal bleeding S3
gasiroieiiinostomy S3
-tube
— bleeding 83
— complication 83
gastrostomy tube
-bleeding 83
- complication 83
GCS, see graduated compression stocking
GDC matrix" coil 244
gelatin sponge 192
-powder 180,223
gelfoam 64,86,91,130,205,224,262,265,311
- embolization 49
-powder 64,242
gene(DNA) 295
- therapy vector 296
- transfer 299
general anesthesia _40
genotype 266
Giacomini vein ablation 122
giant hemangioma 6
gigabec-querel 1 42
Gilbert's syndrome 151
glomeruli 204
glomovenous malformation 22
glucagon 164,181
glue 309
graduated compression stocking (GCS) 123
grays 142
great saphenous vein (GSV) 119
groin bleeding 69
growth factor 170
- inhibitor 150
GSV, see great saphenous vein
Guglielmi detachable coil 93
H
HCC, see hepatocellular a
hemangioendothelioma 248, 306
hemangioma 306, 30S
- arterial embolization 5
- complete resolution 4
- complications 4
-CT 5
-MR 5
- proliferating hemangioma ."■
- strawberry lesion 4
- superficial 4
- surgical removal 5
hemangiopericytoma 248
hematologic purpura 211
hematoma 111
hematuria 202
hemorrhagic shock 35
- severity class 39
hepatectomy 170
hepatic 103
- - iatrogenic embolization Si
- artery aneuryms
- common hepatic artery 105
--multiple 105
- solitary 105
- artery embolization 48, 50, 52
- biological tolerance 169
- encephalopathy 1 80
- epithelioid hemangioendothelioma 308
- hemangioendothelioma 7
--CT 49
- - hepatic injury severity scale 49
- pseudoaneurysm 71
- tumorigenesis 22 1
hepatico-enteric arterial communication 15
hepatitis 129
-B 129
hepatoblastoma 31 8
hepatocellular carcinoma (HCC) 129, 141
hepatocyie
- genome 298
- growth factor (HGF) 164,223
hepatojejunostomy 131
hep a to trophic
-content 164
-factor 163
hereciian"
- spherocytosis 211
-syndrome 201
hereditary hemorrhagic telangiectasia 8, 11
hexokinase 11
- expression 222
- specific inhibitor 111
HGK ,; ;r hepaiocyte growth facior
5-fflAA 225
histoacryl 29,167,305
holmium 166(-166-Ho] 227
hormonal syndrome 177
human yene therapy 29?
hyaluronate 172
hydrocoil 244
hypercalcemia 202
Hypersplenism 211
hypertension 190,210
hypertrophy 163
hyper vascular tumor 190
hyper vascularity 149
hypocalcaemia 190
hypophyseal artery 238
hypotension 202
hypo-vascular tumor 190
hypoxia 223
iatrogenic 34
- injury 79,101
- arterial puncture 91
- arterial rupture 91
- carotid arteries 91
- femoral artery 69
- gastrointestinal bleeding 83
--hepatic 88-90
- - hepatic veins 86
- - intrahepatic pseudoaneurysm SO
--renal 85,90,93
-- renal PTA 91
- renal transplant 90
- subclavian 89
- - subclavian arteries 91
- pseudoaneurysm 100
idiopathic
- epistaxis 262
- thrombocytopenic purpura 317
iliolumbar artery 63
!MA, see inferior mesenteric arterv
immunologic response 239
immunotherapy 201
incidental aneurysm 103
mcependent indicator 224
indium 111 pentetreotide 179
indocyanine gteen retention rale 172
indolent cyst 147
infarction of the bowel 111
- capsular artery 203
-gluteal 63
- artery 191
- mesenteric artery (IMA) 103
-polar artery 212
- tympanic branch 240
inflow artery 10
inhibitor of growth -factor-signaling 222
in-iine stabilization 37
insulin 164
intercellular disjunction 164
intercostal artery 132
interferon 1/^.189,308
interlcukin 2 189
internal
- carotid artery 235,238,249,273
- iliac anery 62, <i4, 65
Subject Index
- maxillary artery 235
- maxillary system 237
- pudendal 63
intestinal angina 110
intraarterial brachy therapy 216
intrahepatic rupture 106
:nt i a ope: alive blooc loss 1 89, 2 1 ' 11 ' 1
:■ 'CizeJ ethyl ester 242
- i r inotec an -elu ting bead 228
irreversible failure ] 55
ischemia 111
ischemic neuropathy
167
.v.i. on 205
J
n-line stabilization
juvenile
-angiofibroma 247,264,312
- nasopharyngeal angiofibrom.
kaposiform hemangioendothelioma 5, 6
Xasabach-Merritt phen
Ki-67 labeling index
kidney
- fracture 53
- renal embolization
- renal injury
- embolization 51
Klippel-Trenaunay s;
landingzone 108
laser 29
lateral
- circumflex femoial ai
- sacral 63
LDL receptor 296
'.t'A gastroepiploic arrei
leucovorin 158
leukemia 211
lidocaine 181
ligation 62
lipiodol 130,180,222,299
- ]3l lipiodol 224
liver 106,149
- abscess 185
- embolization 50
- trophicity 164
longitudinal neural artery 235
lower- extremity chronic venous i
-GSV 119
- sphenous space 120
-SSV 120
- superficial wnous insufficiency
LSF, see lung shunt fraction
lung 149
-shunt fraction (LSF) 152
lymph j iic ma lie-: mat ion 12, 14, 15
lymphoma 211
M
"TmMAA 143
-lung shunting 151
^Tc-MAA 150
macro-aggregated albumin 143
macrophage cell 170
Maffucci's syndrome 22
magic wallstent 285
malignant hypertension 113
Mai Ian'; syndrome 101
mechanical skeletal failure 190
- circumflex femoral artery 191
- emergency 35
metaiodobenzylguanidine (MIBG
microcirculation 150
microcoil 49
microph.ebeciomy 1 21
middle capsular artery 203
mitomycin 222
mucocutaneous familial venous n
multiple renal artery 203
myec-iic aneurysm 105
N
nanotechnology 228
nasc'palatine artery 259
nasopharyngeal angiofibroma 312
NBCA, see n-butyl cyanoacrylate
n-butyl cyanoacrylate (NBCA) 87, 93, 242, 251
- N-butyl-2- cyanoacrylate 225,242, 305, 309
neomtimal hyperplastic restenosis 290
nephron-sparing procedure 113,201
-block 305
- injury 66
neural compression riemaloma I [4
neuroblastoma 248
neurocristopathic tumor 251
neuroendocrine tumor 177
- complication 184
- e\ciusion criteria 1 SO
- hepatic aioery emooiotherapy 1 79
- inclusion criteria 180
-pitfalls 185
-results 184
-survival 184
-tools 181
- treatment algorithm 179
neuroform 285
neuroleptic analgesia 2-10
neuropathy 16,70
neuropeptide 178
neutropenia 185
nidus 16
nitroglycerin 245,305
nitropaste 245
nonchromaffin paiaganglio
nontarget
- embolization 114,144,11:
-radiation 155
obstructive jaundice 166
obturator 63
occipital artery 239,243
occlusion balloon 205
-catheter 204
ontogenesis 235
ophthalmic artery 237,259
-ablation 201
- injury 306
oropharyngeal obstruction 37
Osier- Weber- Rendu syndrome a
outflowvein 10
packing 255
palliative cnrnsiization 209
piir.i-cniii ivc* if. I tumor 177
pancreatitis 100, 111,114
papaverine 101i
..'jjlJiifclii'md 248,251
paraneoplastic •.■yr-iptom 202
■;ar<ithyri"d adenoma 254
paresthesia 124
partial
- hepatic resection 163
-splenectomy 211
- splenic embolization 212
patient work up 101
patient-controlled -anesthesia fPCA) 16
PGA, see patient-controlled -anesthesia
PGoA, see posterior communicating artery
pediatric intervention 303
- arteriogram 63
-fracture 63,65,306
- - algorithm tor t jj e management 62
- classification 61
- - external fixation 62
- - Kane's classification 61
- laparotomy 62
- - mechanism of injury 59
- - radiographs 61
- sources of bleeding 60
- trauma
- hemorrhage 59
- - mortality 59
- -shock 60
— surgery 60
— therapy 63
-biliary drainage 80,81
- venography 26
.•erfoiaimg artery 203
perfusionMRI 137
ye miliary fibrosis 170
periodic EPX 266
peri procedural antibiotic
103
peroneal 71
pharyngo-cutaneous fistula 275
piperacillin 185
platinum fiber microcoil 309
pledget 223
polidocanol 28
polyfbenzy! 1-glutamate) (PBLG) microsphere 22
polyacrylonitrile (PAN) hydrogel 227
polycythemia 202
polyethylene 241
poly-L- lactic acid (PLLA) microsphere 227
polymerization 1 67
polyvinyl alcohol (PVA] 49,86,223,225,226,251
- hydrogel drug-elutingbead 228
-particle 192,214,242,305
- hydrogel 227
- particle 6
-hypertension 211
- pressure 167
- vein embolization I 63
- embolic agenls i *<9
- - growth rate of liver 1 70
- - long-term survival 173
- surgical transileocolic approach 168
- vein patency 106
-vein thrombosis (PVT) 132
per re -anastomosis 1 69
post catheterization j3
postembolization syndrome 103, 145, 196,210
- communicating a: ;ery (PCoA) 276
-EPX 258
- lateral nasal 259
- medial nasal artery 259
postoperative
- bleeding 88
- liver failure 172
posttraumatic AVF 12
precise stent 283
primitive maxillary artery 237
profunda femoris artery 191
picgnoslic factor 177
prominent ethmoidal artery 263
prophylactic
- embolization
202
Vioie'.is syndrome 3b.'
protracted hemorrhage 272
pseudoaneurysm 69,70,80
-of the common carotid artery 276
"ir: ygcvaginal artery 239
- - organ injury score 54
pulling sensation 125
- vascular injury 52
pulmonary
renal
- AVM year 8, 1 1
Rendu-Osler- Weber syndrome 266,310,313,31
- Upiodol embolism 31 8
Renegade 145
- lyiriph-.iiigio.eioiTivomaiosis 202
ien:n-.i:'giotensin 190
PVA. see polyvinyl alcohol
replaced
PVT, see portal vein thrombosis
- leii hepatic artery ; 44
pyrexia Is]
- right hepatic artery 144, 185
resin-based microsphere 141
respiratory obstruction grade 36
R
resuscitation 39,40
radiation
reticuloendothelial hyper plasm 21 1
- dosimetry 145
retroperitoneal bleeding 53, 69
-hepatitis 159
RF ablation 124
- pneumonitis 142, 150, 155
lii.ibdomvos.iicoma 249
- therapy 250
right
:adical nephrectomy 201
- gastric artery 144
:ailioen:oojzauon ! 39
- hepatic artery 144
- calculation of lung dose 155
RNA 295
-complications 146,159
road mapping 191
- discharge instructions 146
rtPA 317
- duodenal ulcers 157
- follow up 147
S
- gastric ulcers 157
saccular
-HCC 141
- microaneurysm
- insoluble sl.-ss microspheres 153
- - amphetamine abuse 101
- liver metastases 149
- - polyarteritis nodosa 101
- materials 146
- pseudo.tneurysm 100
resin based microspheres 154
sacral fracture 63
results 1 [16
sandwich technique 167
raci:if:t\|ui.ncy ablation 140, 170,201
saphenous
-nerve 119
radiotherapy 252
-vein reflux 119
radius 285
sarcoma 139
rCBS, sec ■>.', urrent carotid blowout syntonic
sciatic nerve 193
RCCmetastase 190
sclerosing agenl 28
recanalization 106
sclerotherapy 27,30,316
- ofpseudoaneurysm 106
seizure 114
recombinant
selective internal radiation (SIR) 141
- adenoviral vector 223
-sphere 141,149,154
- P-galactosidase 223
self- expanding stent 281,283
recurrent carotid blowout syndrome (rCBS) 275
sepsis AS
refractory hypertension 314
serotonin 178
renal
- serotonin- sec re ting tumor 1 77
- abscess 210
sev.ia! dysfunction 66
- artery 103
shock 35,60
- artery aneurysm
silicone detachable 278
- - iingiomyolipoma 112
single photon emission ccnip.i'.ed :onioguphy
150
— balloon occlusion catheter 113
SIR, see selective internal radiation
— classification 112
skeletonization 172
— iatrogenic 112
skin
-burn 124
— natural history 1 12
- ulceration 16
— neurofibromatosis 112
SMA 103
- - posl-embolization syndrome 1 1 3
small saphenous vein 119
— surgical repair 113
smart stent 283
— traumatic 112
sodium tetradecyl sulfate 316
- arte j y embolization 51, 52, 207, 216
solid hepatic tumor 129
- cell carcinoma 201 ,207
solitary lesion 190
--bone metastases 189
somatostatin
-failure 113
- analogue 178
- trauma
-receptor 178
sotradecol 28
learlery 239,259
sphere 226
spherical PVA 227
sphincter of Oddi 131
sphincterotomy 131, 185
spidervein 121
splanchnic, aneurysm 109
spleen 46,49
splenic 103
- angiogram 46
-artery 212,214
- artery aneurysm
-- calcified masses 107
- -rupture 107
- .'.rtery embolization 43,45,47,48,21
-infarction 48,109,185
--scale 45
- trauma
- -AV fistula 47,48
GT grades 47
- -CT-based classification 44
- pseudoaneurysm 45,47
- splenic injury scale 45
- pathologic fracture 197
- retroperitoneal hem orr luge 202
stem cell 298
- angioplasty 279
- fracture 71
-graft 71,88,89,104,113,114,285
strawberry hemangioma 4
streptozocin 179
St'ji'ge- Weber syndrome 312
subclavian artery injury 89
sunburst 203
superficial temporal artery 235, 243
superior
- capsular artery 203
- gluteal 63
- gluteal artery 191
- mesenteric artery aneurysm 1 0°
-polar artery 212
surgical metastaseclomy 178
sf.i viva! benefit 139
synthetic materia! 25.-
systemic steroid tr
TAC, see transarlei lal chemotherapy
TACE,see transarteriul chemo embolization
TAE, see transarterial embolization
tamponade 114
tazobaclam 185
tehiiigieciasia 121,267
TGF-a, see transforming growth factor-alpha
thalassemia 317
-major 211
TheraSphere 141,149,154
topography 252
torpedo 49
total splenectomy
- -dual phase 130
- - follow up 137
- - procedure 132
- -results 138
- chemotherapy (TAC) 139
- embolization (TAE) 139
transcatheter aneria! chemoemLiojzaiion 221
transforming growth factor-alpha (TGF-a) i 64
transient ischemia 2PB
transitory carotid occlusion 251
transplant kidney 90
trauma 35,101,306
-blunt 48
- iatrogenic 48
- kidneys 52
-liver 48
- pelvic 59
- solid organ 43
-splenic 43
- visceral 43
pistaxis 264
- of saccular aneurysm 106
-ofSVI 120
Trendelenburg position 123
tris-aciyi gelatin microsphere
truncalvein 120
tuberotis sclerosis 202
tufted angioma 308
tumescent anesthesia 122
- antigen 209
- growth 165
- lysis syndrome 135
- marker 142
- tumor-relaled epistaxis 264
- vessel 203
-viability 137
-volume 165
U
uncovered stent 87
urate-induced renal failure 180
V'AA, ice vi~jcr.iL arieri:
v;'.lri.i';if insufficiency
varicocele 316
121
:ular
- anomaly 21
- endothelial growth factor ( VEGF] 222, 223
- injury <>9
- malformation 3, 83, 306
- supply to the kidney 113
-tumor 30fi
VBCtH.scc sasculai endothelial growth factor
venous malformation 3, 12,23
- arteriography 2-1
- classification 21
- coagulopahies 22
- computed i:im: g-.iphy 24
-diffuse 22
- direct percutaneous venography 25
- endovascular approach 30
-focal 22
- genetics 21
- magne:ic resonance .mag.ng 24
- management 26
-MRI 25,27
- percutaneous approach 30
- peripheral venography l:<
- predominantly venous malformation 2!
- sclerotherapy 26
- ultrasound 23
vei'.n;":.
-aorta 236
- ophthalmic artery 235
- pharv.ige.U artery 236
vidian artery 239
viral hepatitis 172
visceral arteni'.l a usury flu i
- incidence 99
vitamin K 191
v.in llippel : mj,!ii syndror
v:in Kcck!mt>"~itt:M':'.'s disea:
von Willehrand disease 26i
walljiraf: 2S^,2K9
wallstenl 2S3
Wallmar: l<i:ip 104
W:: pp tprnt'Lurt: 88
vvhoiied appearance 203
yttrium-90 (-90-Y] ]
- glass microsphere 1
-microsphere 149
List of Contributors
Volume 2
KamhanAhhar.MD
Section of Interventional R;t dun logy
Division of Diagnostic Imaging
The Univerfity or" Tex a s
MD Anderson Cancer Center
1515 Hokombe Boulevard, Unit 325
Houston, TX 77030-4009
USA
Hortensia Alvarez, MD
Service de Neuroradiologie
et Therapeutique
Hopital Bicetre
78 rue due General Leclerc
94275 Le Kremlin Bicltre
France
John C. Chaloupka, MD, FAHA, FACA
Director of Interventional Neuroradiology
Professor of Radiology and Neurosurgery
University of Iowa Hospitals and Clinics
University of Iowa Carver College of Medicii
200 Hawkins Dr, 3893 JPP
Iowa City, IA 52242
USA
Michael D. Darcy.MD
Professor of Radiologv .-no Surgery
Division or Ui.ignosiic Radiology
Chief, Intervention ill Radiology Section
Washington University School of Medicin
Miillinckrodt Institute of R.idiologv
:" 10 South Kingshighway, 6th Floor
St.Louis,MO 63110
USA
Josee Dubois, MD
Professor of Radiologv
Pediatric and Interventional ]
Department of Medical Imag
Hopital Ste-Justine
3175 C6te Sle-Catherine Roat
Montreal, Quebec H3T 1C5
James R. Duncan, MD, PhD
Assist.;]")! Professor or Radio-ley and Surgery
Mallinclcrodt Institute or' Radiology and
VV.isoington University School of Medicuice
510 S. Kingshighway Blvd
St.Louis,MO 63110
USA
Dominique Elias.MD
Head of Pige stive Surgery Section
Institut Gustave Rousssv
39, Rue Camille Desmoulins
94800 VillejuifCedex
France
Laurent Gakh. M ', '■
Professor or' Radiology
Pediatric and Interventional Radiologist
f'eur-.rtmenr of Medical k'rusiiiH
Hopital Ste-Justine
3175 Cflte Ste-Catherine Road
Montreal, Quebec H3T 1C5
Canada
Christos S. Georgiades, MD. PhD
Assistant Professor or' Radiology and Surge: 1 ;"
Johns Hopkins Medical Institutions
Blalock 545, 600 North Wolfe Street,
Baltimore, MD 21287
USA
Jean-Francois H. Geschwind, MD
Associate Professor of Radiologv. surgery and (
Division of Vascular and
The Russell H. Morgan Dep;
and Radiological Sci
Johns Hookins \' ed io
Blalock 545, 600 North Wolfe Street
Baltimore, MD 21287
USA
Craig B. Glaiberman, MD
instructor, Radiology
Division of Interventional Radiology
Washington University School of Medicine
Malhnckrodt Institute or' Radiology
510 South Km.gshighvvav. :-th Floor
St.Louis,MO 63110
USA
of Contributors
,N,MD
Professor of Radielogv
Director, Vascular and Interventional Radio
University of Iowa
Department of Radiology
200 Hawkins Drive, 3957 JPP
Iowa City, IA 52242
USA
Minako Hayakawa, MI 1
Visiting Assistant Professor of Radiology
University of Iowa Hospitals and Clinics
University o:' low.; Carver College of Med:;
200 Hawkins Dr, 3893 JPP
Iowa City, IA 52242
USA
.i Hf
,MD
Department of Radiology
University Hospitals Gasthuisberg
Herestraat 49
3000 Leuven
He.g.um
Shih-Wei Hsu, MD
Visiting Scholar, University o'i low.! Hospita
and Clinics
University of low.; Carver College of Medic
200 Hawkins Dr, 3893 JPP
Iowa City, IA 52242
USA
Assistant Professor, 1 iepartiuent .:■:' Piagnost
Radiology
Chang Gung Memorial Hospital
K;l' ■l"i- : i.;:ic
Taiwan
Matthew S. Johnson, MD
Associate Professor .:■:' Radiology
I :■ ject-.j- 1 . Section of Interventional Raciioiogv
Indiana University Hospital, UH0279
Department of Radiology
550 Umversiiy Boulevard
Indianapolis, IN 46202-5253
USA
John R. Kachura, MD, FRCPC
Division of Vascular and Interventional Radio
I 'epartiiien: oi Medical Imaging
Toronto General Hospital
200 Elizabeth Street, Eaton South l-454d
Toronto, ON M5G 2C4
C a :i a d a
NeilM.Khilsani.MD
Cornell Vascular
Weill Me.aical Co Lege of Corned Universitv
416 East 55th Street
New York, NY 10022
USA
Paula Klurfan.MD
interventional Neuroradiely Clinical Fellow
1 Vpar;:i-:ii ::' Medical I maging
University of Toronto
Toronto Western Hospital
399 Bat hurst Street
Toronto, Ontario M5T 2S8
Pierre Lasjaunias.MD, PhD
Service de Neuroradiology 1 'nagn.ostique et Therapet
Hopital Bicetre
78 rue due Genera! Leclerc
94275 Le Kremlin Bicetre
SeonKyu Lee, MD, PhD
Assistanl Professor and Staff Neuroradiologist
1 Vparnieni :■:' Medical I maging
University of Toronto
Toronto Western Hospital
#399 Bathurst Street
Toronto, Ontario M5T 2S8
Walter S. Lesley, MD
Chief, Section of Surgical Neuroradiology
Assistani Profess;:'!" .:■:' Radiology
The Texas A&M University Health Science Center
USA
Eleni Liapi, MD
The Russell H. Morgan
and Radiological Scene
lohns Hopkins Medical
Baltimore, MD
USA
David C. Madoff, MD
Section of Interventional Radiology
Division of Diagnostic Imaging
The University of Texas
MD Anderson Cancer Center
1515 Holcombe Boulevard, Unit 325
Houston, TX 77030-4009
USA
Geert Maleux, MD
Department of Radiology
University Hospitals Gasthtusberg
Francis Marshalleck, MD
Assist.i ni Profess;:'!" of Radiology
Indiana University School of Median
Indiana University Hospital
Room 0279, 550 North University Bot
Indianapolis, IN 26202
USA
parrment of liadiolgv
List of Contribute
Robert J. Min.MD
Cornell Vascular
Weil] Medical College of Cornell University
416 East 55th Street
New York, NY 10022
USA
Anne C. Roberts, HD
University of California. 5 an 1 ! iego Medical Center
Division of Vascular and Interventional Radiology
200 West Arbor Drive
San Diego, CA 92103-8756
USA
AlainJ.Roche.MD
Head of Interventional Radiology Section
Professor, Institut Gustave Rousssy
39, Rue Camille Desmoulins
94800 Villejuif Cede*
Georges Rodesch, MD
Service de Neuroradioloie I 'iagiios:L]ue et Ta.eraoeuiique
Hopit.il Foch
40 rue Worth
B.P. 36
92150 Suresnes
France
Riad Salem, MD, MBA
Assistant Profess;;!" .:■!' Radiology and Oncology
Northwestern Memor.r.l Hospital
Department of Radiology
676 North St. Claire, Suite 800
Chicago, IL 60611
USA
Melhem J. Sharafuddin, MD
University of Iowa Hospitals and Clinics
Department of Radiology
200 Hawkins Dr, 3957 JPP
Iowa City, IA 52242
USA
Gary Siskin, MD
Albnnv Medical College
Vascular Radio iogv. Alia
47 New Scotland Avenue
Albany, NY 12208-3479
USA
gSun.MD
Associate Professor of Radiology
Department of Ri-diology
University of Iowa, College of Medicine
200 Hawkins Dr., 3955 JPP
Iowa City, IA 52242
USA
Kong Teng Tan, MB, BCh, FRCS, FRCR
Division of Vascular and Interventional R
r'ear.rtmen: ot Medioal i:':aaiiia
Toronto General Hospital
585 University Avenue, NCSB 1C-563
Toronto, ON M5G 2N2
Canada
Maria Thijs,MD
Department of Ri-diology
Univers.itv Hospital:". Gasthaisberg
Herestraat 49
3000 Leuven
17 Bramble Lane
West Grove, PA 19390
USA
Rajiv Verma, MD
Section of Interventional Radiology
Division of Diagnostic Imaging
The University of Texr.s
MD Anderson Cancer Center
15 15 Holcombe Boulevard, Unit 325
Houston, TX 77030-4009
USA
Lucy A. Wibbenmeyer, MD
University of Iowa Hospitals and Clinics
Department of Ri-diology
200 Hawkins Dr.
Iowa City, IA 52242
USA
Jeffrey J. Wong, MB ChB, BMedSc
University of California, ion Pi ego Medical Center
Division of Vascular and Interventional Radiology
200 West Arbor Drive
San Diego, CA 92103-8756
USA
Contents - Volume 1
General Principles
Em bolo therapy: Basic Principles and Applic
Melhem J. Sharafuddin.Shiliang Sun, and Jaf/
Embolization Tools
Jafar Golzarian, Gary P. Siskin, Melhem ]. Sha
Hidefumi Mimura, and Douglas M. Cols
Controlled Delivery of Pushable Fibered Coils for Large Vessel Embolotherapy
Robert I.White Jr. and Jeffrey S. Pollak 35
Work-up and Follow-up after Embolization
Jim A. Reekers
5 Upper GI Bleeding
Luc Defreyne 49
6 Embolization for Lower GI Bleeding
Michael Darcy 73
7 Haemobilia and Bleeding Complications in Pancreatitis
Tony A.Nicholson 87
8 Balloon-occluded Retrograde Transvenous Obliteration ol Gastric Varices
in Portal Hypertension
Koji Takahashi and Shiliang Sun 99
Gynecology and Obstetrics 105
9 Interventional Management of Postpartum Hemorrhage
Hicham T.Abada, Jafar Golzarian, and Shilliang Sun 107
10 Fibroids
Gary P. Siskin, Jeffrey J.Wong, Anne C. Roberts, Jean Pierre Pelage,
Arnaud Fauconnier, Pascal Lacombe, Alexandre Laurent, and
Jafar Golzarian 119
10.1 Uterine Fibroid Embolization: Practice Development
Gary P. Siskin 119
10.2 Pre-op Work-Up and Post-op Care of Uterine Fibroid Embolization
Jeffrey J.Wong and Anne C.Roberts 125
10.3 Fibroid Embolization: Anatomv and Technical Considerations
Anne C.Roberts 141
336 Contents -Volume 1
10.4 Results and Complications
Jean Pierre Pelage,Arnaud Fauconnier, and Pascal Lacombe 157
10.5 How to Minimize Failure after UFE
Jafar Golzarian and Jean Pierre Pelage 177
10.6 Perspectives
Alexandre Laurent, Jean Pierre Pelage and Jafar Golzarian 187
1 1 Pelvic Congestion Syndrome
Lindsay Machan 199
Genitourinary 213
12 Varicocele Embolization
David Hunter and Galia T.Rosen 215
13 Embolization Therapy for High-Flow Priapis.
Jim A. Reekers
Aortic-Iliac 233
14 Endoleak: Definition, Diagnosis, and Management
David Valenti and Jafar Golzarian 235
15 Internal Iliac Artery Embolization in the Stent-Graft Treatment of
AortoLliac Aneurysms
Mahmood K.Razavi 253
Respiratory Syster
16 Bronchial Artery Embolizatio
Jos C. van den Berg
17 Pulmonary Arteriovenous Malformations
Jean Pierre Pelage, Pascal Lacombe, Robert I. White, Jr.,
and JeffrayS.Pollak 279
Subject Index 297
List of Contributors 303
Contents and List of Contributors of Volume 2 305
List of Contributors -Volume 1
Hicham T.Abada.MD
! Vp.i rl::~.c-jj! a: Imaging and Interve:i1ic-jial Rac.
Centre Hospitalier Rene Dubos
6, Avenue de L'lle-de-France
95303 Cergy Pontoise Cedex
France
Douglas M. Coldwell, MD
Professor of Rao:.\.:gv
University of Texas Southwestern Medical Ce
5323 Harry Hines Blvd.
Dallas, TX 75390-8834
USA
Michael D.Darcy.MD
Professor of Radiologv and Surgery
\iallinckrodt Institute of Radiologv
Washington University School of Medicine
5 10 South Kingsbighway Boulevard
SaintLouis,MO 63110-1076
USA
LucDefreyne.MD
Department of Vascular and
Interventional Radiology
Ghent University Hospital
De Pintelaan 185
9000 Ghent
oe^giu:;".
Arnaud Fauconnier, MD, PhD
Department of Obstetrics and Gynecologv,
Centre Hospitalier de Poissy,
10, rue du Champ Gaillard,
78300 Poissy Cedex,
Iafar Golzarian,MD
Professor of Radiologv
Director, Vascular and Interventional Radiol
University of Iowa
Department of Radiology
200 Hawkins Drive, 3957 JPP
Iowa City, IA 52242
USA
David W. Hunter, MD
Department of Radiology
"2-447 Fairvjew-Lniversity Medical Center
University of Minnesota
500 Harvard Street S.E.
Minneapolis, MN 55455
USA
Pascal Lacombe, MD
Department of Radiologv H ■ : y i t n I Amhroise :
9, Avenue Charles De Gaulle
92104 Boulogne Cedex
France
Alexandre Laurent, MD, PhD
Associate Professor
Center for Research in
Interventional Imaging (Cr2i APHP-INRA)
Jouy en Josas, 78352
France
Lindsay Machan, MD
Department of Radiology
University of British Columbia Hospital
2211 Wesbrook. Mall
Vancouver, BC V6T 2B5
HlDEFUMl Ml.MURA, MD
Associate Professor of Radiologv
University of Iowa Hospitals and Clinics
Department of Radiology
200 Hawkins Dr, 3957 JPP
Iowa City, IA 52242
USA
Tony A. Nicholson, BScM, Sc, MB, ChB, FRCR
Consultant Vascular Radiologist & Senior Lecture
Leeds Teaching Hospitals NHS Trust
Great George Street
Leeds, LS13EX
UK
[ean-Pierre Pelage, MD, PhD
Department of Radiology
HopitalAmbroisePare
9, Avenue Charles De Gaulle
92104 Boulogne Cedex
France
TeffreyS.Pollak.MD
Yale University School of Medicine
Department Diagnostic Radiology
PO Box 20842
New Haven, CT 06504-8042
USA
Mai
d K. Ra:
ri, MD
Center tor Research and Clinical
St. Joseph Vascular Institute
LJ := ; of Contributors -Volume 1
Jim A. Reekehs, MD, PhD
Department of Radiology, G 1-207
Academic Medical Center
University or' Amsterdam
Meibergd reef i_;
AZ 1105 Amsterdam
The Netherlands
Anne C. Roberts, MD
University of California, San Diego Medic;
Division of Vascular and
Intervention.;! Radiology
200 West Arbor Drive
San Diego, CA 92103-8756
GaliaT. Rosen.MD
Department of Radiology
J2-447 Fair view-University Medical Center
University of Minnesota
500 Harvard Street S.E.
Minneapolis, MN 55455
USA
Melhem J. Sharaflddin, MD
Departments of Radiology and Surgery, 3JPP
University of iowa Hospitals and Clinics
200 Hawkins Drive
Iowa City.IA 52242-1077
USA
Gary P. Siskin, MD
Associate Professor of Radiology a:
Obstetrics fx Gynecology
Albany Medical College
47 New Si". :~..,\ nci Avenue, MC- 1 i. ;
Albany, NY 12208-3479
USA
Shiliang Sun.MD
Associate Processor of Radi.ikgv
University of Iowa Hospitals and Clii
200 Hawkins Dr, 3955 JPP
Iowa City, IA 52242
USA
KojiTakahashi.MD
Department of Radiology
Asahikawa Medical College
2-1-1-1 Midorigaoka
Asahikawa, 078-8510
los C. VAN DEN Bebg, MD, PhD
Head or' Service t-A inter vein ion.il Rao iology
Ospedale Regionale di Lugano, sede Civico
Via Tesserete 46
6900 Lugano
Switzerland
David A. Valenti, MD
Royal Victor;.; Hospital
McGill University Health Centre
McGill University
687 Pine Avenue West, Suite A451
Montreal, Quebec H3A 1AI
Robert I. White, Jr., MD
Yale University School of Medicine
Department of Diagnostic Radiology
333 Cedar Street, Room 5039 LMP
New Haven, CT 06520
USA
Jeffrey J. Wong, MB ChB, BMedSc
Senior House Officer
Royal National Orthopaedic Hospital
MEDICAL RADIOLOGY Diagnostic Imaging and Radiation Oncology
Titles in the series ,i/rv<i,fi published
Diagnostic Imaging
Radiology of the Upper Urinary Tract
Edited by E.K.Lang
The Thymus -Diagnostic Imaging,
functions, and Pathologic Anatomy
Edited by E. Walter, E. Willich,
andW.R.Webb
Interventional Neuroradiology
Edited by A. Va lava n is
Radiology of the Pancreas
EditedbyA.L.Baert,
, _ o-ediied by G. Pelorme
Radiology of the Lower Urinary Tract
Edited by E.K. Lang
Magnetic Resonance Angiography
Edited by I, P.Arlart, G. M. Bongartz,
andG.Marchal
Contrast -Enhanced MRI of the Breast
S. Heywang-Kobrunner and R. Beck
SpiralCToftheChest
Edited by M. Remy-Jardin and J. Remy
Radiological Diagnosis of Breast Diseases
Edited by M. Friedrich and E. A. Sickles
Radiology of theTrauma
Edited by M. Heller and A.Fink
Biliary Tract Radiology
Edited by P.Rossi,
co-edited by M. Brezi
Radiological Imaging of Sports Injuries
Edited by C.Masciocchi
Modern Imaging of the Alimentary Tube
Edited bv A. R. Margulis
Diagnosis and Therapy of Spinal Tumors
Edited bvP.R.Algra, ]. Vaik,
andJ.J.Heimans
Interventional Magnetic
Resonance Imaging
Edited by J.F.Debatin and G.Adam
Abdominal and Pelvic MRI
Edited by A. Heuck and M. Reiser
Orthopedic Imaging
Techniques and Applications
Edited by A.M. Davies
and H. Pettersson
Radiology of the Female Pelvic Organs
Edited by E.K.Lang
Magnetic Resonance of the Heart
and Great Vessels
Clii)k\il Applications
Edited by J. Bogaert, A.J. Duerinckx,
andF.E.Rademakers
Modern Head and Neck Imaging
Edited by S.K.Mukherii
andJ.A.Castelijns
Radiological Imaging
of Endocrine Diseases
Edited by J.N. Bruneton
in collaboration with B. Padovani
andM.-Y.Mourou
Trends in Contrast Media
Edited bv H. S. T horns e n.
R.N.Muller.andR.F.Mattrey
Functional MR]
Edited by C. T. W. Moon en
andP.A.Bandettini
Radiology of the Pancreas
2nd Revised Edition
Edited by A. L. Baert. Co-edited by
'.j. ', ! elorme ,u:d L.Van Hoe
Emergency Pediatric Radiology
Edited by H.Carty
Spiral CT of the Abdomen
Edit;," by r. Terrier, X. Crossholz.
and C.D.Becker
Liver Malignancies
Diagnostic and
Interventional Radiology
Edited by C. Rai'talozzi
Medical Imaging of the Spleen
Edited by A.M. De Schepper
and F.Vanhoenacker
Radiology of Peripheral Vascular Diseases
Edited by E.Zeitler
Diagnostic Nuclear Medicine
Edited oy C. ^ohiepers
Portal Hypertension
Diagnostic Imaging-Guided Therapy
Edited bv P. Rossi
Co-edited by P. Ricci and L. Broglia
Recent Advances in
Diagnostic Neuroradiology
Edited by Ph. Demaerel
Virtual Endoscopy
and Related 3D Techniques
Ed.:ed bv ?. Rog.^Kj, I. Terwisschj
Van Scheltinga, and B.Hamm
Multislice CT
Edited by M. F. Reiser, M. Takahashi,
M. Modic, and R. Bruening
Pediatric Uroradiology
Edited by R. Fotter
Transfontanellar Doppler Imaging
In Neonates
A. Couture and C.Veyrac
Radiology of AIDS
A Prarlical Approach
Edited by J.W.AJ. Readers
and P.C.Goodman
CT of the Peritoneum
Arm.iiido Rossi and Giorgio Rossi
Magnetic Resonance Angiography
2nd Revised Edition
Edited by I. P.Arlart,
G.M. Bongratz, and G. Marchal
Pediatric Chest Imaging
Edited by Javier Lucaya
and Janet L. Strife
Applications of Sonography
In Head and Neck Pathology
Edited by J. N. Bruneton
in collaboration with C. Raffaelh
andO.Dassonville
Imaging of the Larynx
Edited by R.Hermans
3D Image Processing
Techniques and Clinical Applications
Edited by D. Caramella
and C. Bartolozzi
Imaging of Orbital and
Visual Pathway Pathology
Edited by W. S. Miiller-Forell
Pediatric ENT Radiology
Edited by S.J.King
and A. E.Boothroyd
Radiological Imaging of the Small Intestine
Edited by N. C. Gourtsoyiannis
MEDICAL RADIOLOGY Diagnostic Imaging and Radiation Oncology
Titles in the series already published
Imaging of the Knee
Techniques and Applications
Edited by A.M. Davies
andVN.Cassar-Pullicino
Perinatal Imaging
From Ultrasound (a MR Imaging
Edited by Fred E.Avni
Radiological Imaging of the Neonatal Chest
Edited by V.Donoghue
Diagnosticand Interventional
Radiology in Liver Transplantation
Edited by E. Biicheler, V. Nicolas,
C.E.Broelsch.X-Rogiers,
and G. Krupski
Radiology of Osteoporosis
Edited by S. Grampp
Imaging Pelvic Floor Disorders
Edited by C.I. Bartram
and J. 0. L.DeLancey
Associate Editors: S. Halligan,
F.M. Kelvin, and J.Stoker
Imaging of thePancreas
Cystic and Rare Tumors
Edited by C.Procacci
and A.J. Megibow
High Resolution Sonography
of the Peripheral Nervous System
Edited by S. Peer and G. Bodner
Imaging of the Foot and Ankle
Techniques and Applications
Edited by A.M. Davies,
R.W.Wh'itehouse,
and J. P. K. Jenkins
Radiology Imaging of the Ureter
Edited by F. Joffre, Ph. Otal,
and M. Soulie
Imaging of the Shoulder
Techniques and Applications
Edited by A. M. Davies and J. Hodler
Radiology of the Petrous Bone
Edited by M. Lemmerting
andS.S.Kollias
Interventional Radiology in Cancer
Edited by A.Adam, R. F. Dondelinger,
andP.R.Mueller
Duplex and Color Doppier Imaging
ofthe Venous System
Edited by G.H.Mostbeck
Mu It i detector-Row CT of the Thorax
EditedbyU.J.Schoepf
Functional Imaging ofthe Chest
Edited by H.-U.Kauczor
Radiology of the Pharynx
and the Esophagus
Edited by O.Ekberg
Radiological Imaging
tn Hematological Malignancies
Edited by A.Guermazi
Imaging and Intervention in
AbdomlnalTrauma
Edited by R. F. Dondelinger
MultisliceCT
2nd Revised Edition
Edited by M. F. Reiser, M. Takahashi,
M.Modic, and C.R.Becker
Intracranial Vascular Malformations
and Aneurysms
From Diagnostic Work-Up
to Endovascular Therapy
Edited by M.Forsting
Radiology and Imaging ofthe Colon
Edited by A.H. Chapman
Dynamic Contrast -Enhanced Magnetic
Resonance Imaging in Oncology
Edited by A. Jackson, D. L. Buckley,
and G.J. M.Parker
Imaging in Treatment Planning
forSinonasalDiseases
Edited by R. Maroldi and P. Nicolai
ClinicalCardlacMRI
With Interactive CD-ROM
Edited by J.Bogaert,
S. Pym;"! j' ho wjki, ai:d A. M. Taylor
Focal Liver Lesions
Detection, Characterization,
Ablation
Edited by R. Lencioni, D. Cioni,
andC.Bartolozzi
Multidetector-RowCT Angiography
Edited by C.Catalano
andR.Passariello
Paediatric Musculoskeletal Diseases
With an Emphasis on Ultrasound
Edited by D.Wilson
Contrast Media in Ultrasonography
Basic Principles and Clinical Applications
Edited by Emilio Quaia
MR Imaging in White Matter Diseases of the
Brain and Spinal Cord
Edited by M. Filippi, N. De Stefano,
V. Dousset, and J. C. McGowan
Diagnostic Nuclear Medicine
2nd Revised Edition
EJite." bv C. Sohieper:;
Imaging ofthe Kidney Cancer
Edited by A.Guermazi
Magnetic Resonance Imaging in
Ischemic Stroke
Edited by R. von Kummer and T. Back
Imaging of the Hip S Bony Pelvis
Techniques and Applications
Edited by A. M. Davies, K. J. Johnson,
andR.W.Whitehouse
Imaging of Occupational and
Environmental Disorders ofthe Chest
Edited by P.A.Gevenois and
P.DeVuyst
Contrast Media
Safety Issues and ESL'R Guidelines
Edited by H. S. Thorn sen
Virtual Colonoscopy
A l'i .uTiiiil Guide
Edited by P. Lefere and 5. Gryspeerdi
Vascular Embolotherapy
A Comprehensive AppiuaJi
Volume 1
Edited bv i. Golzarian. Go -edited bv
S.SunandMJ.Sharafuddin
Vascular Embolotherapy
A Cuinpn'liensive Approach
Volume 2
Edited bv i. Golzarian. Go -edited bv
S.SunandMJ.Sharafuddin
Head and Neck Cancer Imaging
Edited by R. Hermans
Vascular Interventional Radiology
Current Evidence in End ova Millar
Surgery
Edited by H. G. Cowling
4Q Springer
MEDICAL RADIOLOGY Diagnostic Imaging and Radiation Oncology
Titles in the series ahead) published
Radiation Oncology
Lung Cancer
Edited by C.W.S.
Innovations in Radiation Oncology
Edited by H.R. Withers
and L. J. Peters
Radiation Therapy
of Head and Meet Cancer
Edited by G.E.Laramore
Gastrointestinal Cancer-
Radlatlon Therapy
Edited by R.R. Dobelbower, Jr.
Radiation Exposure
and Occupational Risks
Edited by E. Scherer, C. Streffer,
and K.-R. Trott
Radiation Therapy of Benign Diseases
A Clinical Guide
S.E. Order and S.S.Donaldson
Interventional Radiation
Therapy Techniques- Bra chytherapy
Edited by R. Sauer
Radlopathology of Organs andTissues
Edited by E. Scherer, C. Streffer,
and K.-R. Trott
Concomitant Continuous Infusion
Chemotherapy and Radiation
Edited by M. Rotman
and C. J. Rosenthal
Intraoperative Radiotherapy -
Clinical Experiences and Results
Edited by R A. Calvo, M. Santos,
and L.W.Brady
Radiotherapy of Intraocular
and Orbital Tumors
Edited by W.E.Alberti and
R.H.Sagermar,
Interstitial and Intracavitary
Thermoradiotherapy
Edited by M. H. Seegenschmiedt
and R. Sauer
Hon-Disseminated Breast Cancer
Controversial Issues in Management
Edited byG. H.Fletcher and
S.H, Levitt
Current Topics in
Clinical Radloblology of Tumors
Edited by H.-P.Beck-Bornholdt
Practical Approaches to
Cancer Invasion and Metastases
A Compendium of Radiation
Oncologists' Responses to 40 Histories
Edited by A. R.Kagan with the
Assistance of R. J. Steckel
Radiation Therapy in Pediatric Oncology
EditedbyJ.R.Cassady
Carcinoma of the Kidney andTestis,
and Rare Urologic Malignancies
Innovations in Management
Edited by Z. Petrovich, L. Baert,
and L.W.Brady
the
Late Sequelae In Oncology
Edited by J.Dunst and R. Sauer
Mediastinal Tumors. Update 1995
Edited by D.E.Wood
and G.R. Thomas, Jr.
Thermoradiotherapy
andThermochemotherapy
Volume 1:
Biology, Physiology, and Physics
Volume 2:
Clinical Applications
HJili." :'v M.H. ?e egensihi'iieJi.
P. Fessenden, and C.C.Vernon
Carcinoma of the Prostate
Innovations in Management
Edited by Z. Petrovich, L. Baert,
and L.W.Brady
Radiation Oncology
of Gynecological Cancers
Edited by H.W.Vahrson
Carcinoma of the Bladder
Innovations in Management
Blood Perfusion and
Mlcroenvlronment of Human Tumors
Implications for
CI in ical Ra d i o o n cology
Edited by M.Molls and P.Vaupel
Radiation Therapy of Benign Diseases
A Clinical Guide
2nd Revised Edition
S.E. Order and S. S. Donaldson
Progress and Perspectives
Treatment of Lung Cancer
Edited by P. Van Houtte,
J. Klastersky, and P. Rocmans
Combined Modality Therapy of
Central Nervous System Tumors
Edited by Z. Petrovich, L. W. Brady,
\!. L. Apuzzo, and M. Bamberg
Age-Related Macular Degeneration
Current Treatment Concepts
Edited by W. A. Alberti, G. Richard,
andR.H.Sagerman
Radiotherapy of Intraocular
andOrbitalTumors
2nd Revised Edition
Edited by R.H.Sagerman,
andW.E.Alberti
Modification of Radiation Response
Cytokines, Growth Factors,
and Other Biolgical Targets
Edited by C.Nieder, L. Milas,
andK.K.Ang
Radiation Oncology for Cure and Palliation
R.G.Parker,N.A.Janjan,
andM.T.Selch
Clinical Target Volumes In Conformal and
Intensity Modulated Radiation Therapy
A Clinical Guide to Cancer Treatment
Edited by V. Gregoire, P. Scalliet,
and K. K. Ang
Advances in Radiation Oncology
In Lung Cancer
Edited by Branislav Jeremic
Hew Technologies In Radiation Oncology
Edited by W. Schlegel, T. Bortfeld,
and A.-L.Grosu
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