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and too small for catheter placement, aspiration should be attempted
(if technically feasible) to help guide antibiotic treatment (Fig. 4).
Drainage catheters should remain in place until output is low and
clear for several days. As drainage clears, providers should watch for
bile in the drains, which may indicate abscess communication with
the biliary tree. Suspicion for biliary tree communication should be
investigated with hepatobiliary iminodiacetic acid (HIDA) or magnetic resonance cholangiopancreatography (MRCP)/endoscopic retrograde cholangiopancreatography (ERCP). Abscess communication
with a large bile duct may mandate additional drainage procedures
such as sphincterotomy or percutaneous biliary drain placement.
Surgical Drainage or Resection
Antibiotics plus percutaneous drainage is an effective treatment
strategy for 80% to 90% of patients; however, in the rare cases that
fail a percutaneous treatment strategy—more often large, multiloculated abscesses or abscesses that communicate with the biliary
tree—surgery may be required. In general, minimally invasive surgery is preferred, although the recommended approach depends on
abscess location and etiology, as some situations, such as PLA with
simultaneous diverticulitis and intraabdominal abscesses, may be
best served by laparotomy.
Although some studies advocate partial hepatectomy of a diseased segment as the optimal definitive treatment strategy for large
and multiloculated abscesses that fail percutaneous drainage, there is
no evidence that this method is superior to standard surgical drainage with irrigation and drain placement. Moreover, manipulation of
diseased liver during resection may result in acute septic shock.
FIG. 4 MR images show decreased size of abscess cavity.
Outcomes
Outcomes have improved dramatically with expedited diagnosis,
antibiotics, and percutaneous catheter drainage. However, mortality remains high, between 4% and 10%. Retrospective studies have
found that diabetes mellitus, underlying malignancy, and cirrhosis
are associated with increased length of stay and increased mortality.
Studies have also shown that abscess size is an independent risk factor for prolonged hospitalization and mortality. This may be a function of higher bacterial load, more severe inflammatory syndrome,
and increased extrahepatic manifestations. In one series, more than
one-half of patients with abscesses >10 cm had an ipsilateral pleural
effusion and an increased risk of liver abscess rupture with subsequent purulent peritonitis.
AMEBIC LIVER ABSCESS
ALAs, caused by the protozoan E. histolytica, are a common source
of hepatic abscess worldwide and should be considered in the differential diagnosis among patients with suspected PLA. However, most
cases of ALA in the United States are seen in male patients (8:1 maleto-female predominance) with a history of travel to an endemic area.
Pathophysiology
ALA arises from colonic amebiasis, where ingestion of mature protozoan cysts or trophozoites through fecally contaminated food or
water leads to colitis with trophozoite invasion of intestinal mucosa.
In patients with ALA, trophozoites seed the liver through the portal
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system. This process typically occurs 2 to 4 months after symptoms
of colonic amebiasis. Abscesses contain necrotic hepatocytes and trophozoites in a thick, proteinaceous, brown fluid, classically described
as “anchovy paste.”
Diagnosis
As with PLA, patients with ALA present with fever (80%) and
right upper quadrant pain (60%). They often have leukocytosis and
elevations in alkaline phosphatase, bilirubin, and transaminases.
Although E. histolytica is a protozoan parasite, eosinophilia is not
commonly seen. ALA cannot be reliably differentiated from PLA on
imaging.
Given the similarity of presentation between PLA and ALA,
providers must be sure to ask about travel history and to ask about
history of remote antecedent diarrheal illness. All patients with
recent travel to an endemic area should undergo further diagnostic
testing with serology.
Amebic serologic testing (antibody or antigen) is highly sensitive
and is useful to rule out ALA. Antigen testing is more specific than
antibody serology, as one-third of patients with prior E. histolyt-
ica infection will have antibodies even if they do not have active
infection.
Treatment
Antibiotics
Treatment of ALA requires treatment of both the liver abscess and
its source: colonic amebiasis. Oral metronidazole (500–750 mg three
times daily for 7–10 days) is highly effective treatment for ALA, with
clinical improvement in over 90% of patients. However, an additional
antiparasite regimen is required to eliminate intestinal cysts and prevent recurrence, typically oral paromomycin (10 mg/kg three times
daily for 7 days) or oral diiodohydroxyquin (650 mg three times daily
for 20 days).
Whereas treatment duration for PLAs is guided by resolution
of abscess on imaging, ALA treatment duration is standardized as
appropriate antibiotic regimens will lead to quick clinical recovery
in most patients. Repeat imaging is still recommended, but abscess
resolution may take several months and is not necessary for antibiotic cessation.
Drainage
Another critical difference in management of ALAs as compared
with PLAs is that aspiration/drainage is only recommended when
there is no clinical response to antibiotic therapy alone. This is not
because there is increased risk with manipulation of ALA (routine
percutaneous aspiration of hydatid cysts caused by Echinococcus
granulosus is discouraged given the risk of anaphylaxis), but simply
because prospective studies have failed to demonstrate any benefit to
early drainage.
In cases that fail to respond to standard ALA therapy, clinicians
should broaden antibiotics to include coverage for PLA, as bacterial
secondary infections are not uncommon, and they should pursue
percutaneous catheter drainage.
FUNGAL HEPATIC ABSCESS
seen in immunocompromised patients. Those at highest risk include
patients who have undergone orthotopic liver transplantation (OLT)
or hematopoietic stem cell transplantation (HSCT), patients with
human immunodeficiency virus (HIV), and patients with hepatobiliary malignancy. As with PLAs, there are multiple possible sources
of infection. Patients undergoing OLT may develop hepatic artery
thrombosis, which can lead to intrahepatic cholangiopathy that
predisposes them to the development of fungal abscess; patients
undergoing HSCT may experience breakdown of the intestinal
mucosal barrier with translocation of candida from the gut into the
portal system; and patients with hepatic tumors who have undergone
ablation may be left with a fertile necrotic lesion that becomes superinfected with fungi.
These abscesses are associated with the highest risk of death, with
retrospective studies demonstrating that almost one-half of patients
with fungal hepatic abscesses succumb to disseminated infection.
Even with appropriate antifungal treatment, mortality remains
around 20%.
Treatment
Prompt recognition of mycotic infection is critical, and clinicians
must maintain a high index of suspicion for fungal infection in
at-risk patients. In transplantation, the risk of developing invasive
fungal infections is mitigated by routine antifungal prophylaxis,
and mortality in transplant patients with fungal hepatic abscess has
improved with early empiric antifungal coverage.
Fungal liver abscesses are managed according to the same treatment paradigm as PLAs: antimicrobials and percutaneous drainage.
As with PLAs, antifungal treatment should be guided by culture
data, and duration of treatment should be determined by resolution
of lesions on repeat imaging. Most fungal liver abscesses are caused
by Candida spp., and either amphotericin B or an echinocandin such
as caspofungin or micafungin would be appropriate empiric therapy.
S u g g e S t e d R e a d i n g S
Blessmann J, Binh HD, Hung DM, Tannich E, Burchard G. Treatment of
amoebic liver abscess with metronidazole alone or in combination with
ultrasound-guided needle aspiration: a comparative, prospective and ran-
domized study. Trop Med Int Health. 2003;8(11):1030–1034.
Hope WW, Vrochides DV, Newcomb WL, Mayo-Smith WW, Iannitti DA.
Optimal treatment of hepatic abscess. Am Surg. 2008;74(2):178–182.
Huang CJ, Pitt HA, Lipsett PA, et al. Pyogenic hepatic abscess. Changing
trends over 42 years. Ann Surg. 1996;223(5):600–609.
Lee CH, Jo HG, Cho EY, etal. Maximal diameter of liver abscess independently
predicts prolonged hospitalization and poor prognosis in patients with
pyogenic liver abscess. BMC Infect Dis. 2021;21(1):171.
Lin H-F, Liao K-F, Chang C-M, Lin C-L, Lai S-W. Correlation between proton
pump inhibitors and risk of pyogenic liver abscess. Eur J Clin Pharmacol.
2017;73(8):1019–1025.
Lipsett PA, Huang CJ, Lillemoe KD, Cameron JL, Pitt HA. Fungal hepatic
abscesses: Characterization and management. J Gastrointest Surg Off J Soc
Surg Aliment Tract. 1997;1(1):78–84.
Meddings L, Myers RP, Hubbard J, etal. A population-based study of pyogen-
ic liver abscesses in the United States: incidence, mortality, and temporal
trends. Am J Gastroenterol. 2010;105(1):117–124.
Mohan BP, Meyyur Aravamudan V, Khan SR, etal. Prevalence of colorectal
cancer in cryptogenic pyogenic liver abscess patients. Do they need
screening colonoscopy? A systematic review and meta-analysis. Dig Liver
Dis Off J Ital Soc Gastroenterol Ital Assoc Study Liver. 2019;51(12):1641–
1645.
Neill L, Edwards F, Collin SM, etal. Clinical characteristics and treatment
outcomes in a cohort of patients with pyogenic and amoebic liver abscess.
BMC Infect Dis. 2019;19(1):490.
LIVER 401
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Transarterial Therapies
for Primary and
Metastatic Liver Tumors
Nariman Nezami, MD, and Clifford R. Weiss, MD
INTRODUCTION
Image-guided locoregional therapies play an important role in the
treatment of patients with primary or metastatic hepatic tumors.
Today, various intraarterial therapeutic modalities (Fig. 1) are available,
ranging from bland embolization (BE), transarterial chemoembolization (TACE), drug-eluting beads chemoembolization (DEB-TACE), to
selective internal radioembolization therapy (SIRT), or even hepatic
artery infusion (HAI). The rationale behind intraarterial therapies is
to reduce systemic toxicity while offering more effective local tumor
control. Extensive evidence has supported the benefit of image-guided
locoregional therapies, which eventually resulted in the addition of some
of procedures to the National Comprehensive Cancer Network treatment guidelines. This chapter reviews how intraarterial therapies (IATs)
could be incorporated into a multidisciplinary approach, with the goal of
treating cholangiocarcinoma and metastatic liver tumors to downstage
for resection, as a bridge to transplantation, or to provide palliation.
TRANSARTERIAL THERAPIES
The normal liver parenchyma has a dual blood supply; mainly, it is
supplied by the portal vein (70%–75%), which delivers deoxygenated
blood from the small intestine and contains nutrients, while 25%
FIG. 1 Transarterial embolization approaches. (A) BE. (B) cTACE. (C) DEB-TACE. (D) SIRT.
402 TRANSARTERIAL THERAPIES FOR PRIMARY AND METASTATIC LIVER TUMORS
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A
B
CD
FIG. 2 Bland embolization in a patient with numerous NET liver metastases. (A) Axial arterial enhanced MRI shows multifocal metastatic lesions in both
hepatic lobes, with the major burden in the right hepatic lobe. (B) Digital subtraction angiogram also reveals multifocal tumor blush in the right hepatic
lobe. (C) Digital subtraction angiogram shows selective angiogram and bland embolization of segment VI. (D) Axial arterial-enhanced MRI after 4 weeks
demonstrates multifocal tumor necrosis and partial response. (Courtesy Dr. Aran Chary, Emory University School of Medicine.)
to 30% is supplied by the hepatic artery, which delivers oxygenated
blood from the general circulation. The efficacy of TACE relies on
the fact that primary and secondary liver neoplasms are exclusively
fed by hepatic artery branches because of tumor-induced neoangiogenesis. Therefore, the intraarterial delivery of a tumoricidal drug
will primarily target tumor cells, while sparing the liver parenchyma.
Currently, there are four different intraarterial therapeutic options
for treating patients using a catheter-based approach. Multiple
studies have failed to show whether the efficacy of any of these
approaches is superior to the others. Thus, the choice of a transarterial approach is operator/institution-dependent and sometimes
depends on the patient’s arterial anatomy (multiple blood supply to a
tumor or an existing significant shunt).
Bland Embolization
The rationale for the use of BE for hypervascular tumors is that the
majority of tumors are perfused by the hepatic artery. BE results in
antitumor effects solely by blocking blood supply and inducing ischemia and infarction of tumor tissue. During BE, embolic particles are
used to achieve complete stasis in the hepatic artery branches that
supply the target tumor (Fig. 2). TAE could be nearly as effective as
TACE. Therefore, the patient could still benefit from embolization if
chemotherapy is contraindicated (e.g., maximum amount of lifetime
doxorubicin is reached or the patient is allergic).
Conventional Transarterial Chemoembolization
Conventional transarterial chemoembolization (cTACE) is referred
to as Lipiodol-based TACE. This is the originally described conventional TACE method. It involves the transcatheter delivery of a
mixture of chemotherapy and lipiodol into the target tumor, followed
by particle embolization (Fig. 3). The chemotherapy mixture consists
of any combination of cisplatin (100 mg), doxorubicin (50 mg), and
mitomycin C (10 mg). This is mixed with lipiodol (Ethiodol) in a 1:1
or a 2:1 (chemotherapy:lipiodol) volume ratio depending on flow
characteristics. The aqueous-to-lipid phase ratio affects the emulsion
stability and the drug release rate. A 1:1 ratio is more viscous and is
used for high-flow states, whereas the 2:1 ratio is less viscous and is
used in low-flow states.
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A
C
B
D
FIG. 3 cTACE in a 70-year-old woman with intrahepatic cholangiocarcinoma. (A) Axial arterial enhancement MRI shows a large intrahepatic cholangiocar-
cinoma in the right hepatic lobe. (B) Digital subtraction angiogram reveals tumor blush in the right hepatic lobe and blood supply from the right hepatic
artery. (C) Immediate postembolization axial noncontrast CT shows dense lipiodol deposition within the tumor. (D) Axial arterial enhancement MRI after
4 weeks shows extensive tumor necrosis.
Drug-Eluting Beads Transarterial
Chemoembolization
One of the latest developments is the introduction of spongelike
particles that can be preloaded with chemotherapeutics. These particles are used to embolize the target tumor similar to conventional
TACE without the addition of lipiodol. Over a period of time, these
particles elute chemotherapy drugs, maintaining a high intratumoral
dose and a low plasma concentration. DEBs allow only one chemotherapy drug to be loaded, which is most commonly doxorubicin or,
recently, irinotecan.
Selective Internal Radiation Therapy
SIRT is the intravascular administration of microspheres that contain
a radioisotope, which allows delivery of a higher dose of radiation
directly to the tumor than traditional radiation with an external
beam, while exposing healthy liver tissue to only a small dose. SIRT
has been proven to be safe and effective, and is recommended for
patients with unresectable tumors who are refractory to systemic
therapy and have liver-only or liver-dominant disease. The injected
microspheres embolize the microvasculature surrounding the tumor
and emit high-energy beta-radiation. The normal liver parenchyma
is largely spared since healthy liver tissue is mainly supplied by the
portal vein.
Microspheres (∼30 m) are loaded with radioactive isotopes, such
as yttrium-90 (
a microcatheter in the hepatic artery.
90
Y) or holmium-166 (
166
Ho), and delivered through
90
Y-resin microspheres (SIRSpheres, Sirtex) are Food and Drug Administration (FDA)-approved
and CE-marked for treatment of metastatic colorectal can-
90
cer.
166
and
Ho microspheres (QuiremSpheres, Quirem) are CE-approved
for this indication but are not FDA-approved.
166
Ho microspheres are
the most recently developed agents that emit high-energy β particles
while also producing γ radiation, which allows for quantitative, single-photon emission computed tomography (SPECT) imaging. Interestingly,
166
Ho microspheres are paramagnetic, enabling monitoring
with magnetic resonance imaging (MRI).
Two approaches have been described for SIRT: lobar or sublobar
(Fig. 4) versus segmentectomy (Fig. 5). A lobar or sublobar approach
404 TRANSARTERIAL THERAPIES FOR PRIMARY AND METASTATIC LIVER TUMORS
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A
B
C
FIG. 4 Lobar SIRT in 65-year-old man with colorectal liver metastases. (A) Axial PET CT scan shows extensive FDG avidity in the right hepatic lobe. (B)
Digital subtraction angiogram reveals tumor blush in the right hepatic lobe and blood supply from the right hepatic artery. (C) Intraprocedural cone-beam
CT scan confirms corresponding perfusion. (D) Nuclear medicine SPECT CT immediately post-MAA mapping/shunt study shows MAA deposition within
the tumor region. (E). Nuclear medicine SPECT CT demonstrates dense resin-based 90Y retention within the right hepatic lobe. (F) Axial PET CT scan
shows partial response in the right hepatic lobe tumor. (Courtesy Dr. Aran Chary, Emory University School of Medicine.)
D
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B
A
C
FIG. 5 SIRT, segmentectomy in a 58-year-old woman with a surgical history of colectomy, cholecystectomy, right hepatectomy, on multiple lines of
chemotherapy and SIRT with a single colorectal liver metastasis. (A) Axial arterial enhanced CT scan shows a single metastasis in the right hepatic lobe.
(B) Digital subtraction angiogram reveals tumor blush with corresponding blood supply from segment VII of the hepatic artery. (C) Intraprocedural cone-
beam CT confirms the corresponding perfusion from segment VII of the right hepatic artery branch. (D) Nuclear medicine SPECT CT demonstrates dense
glass-based 90Y retention within the tumor. Immediate post-SIRT SPECT CT shows dense 90Y glass deposition within the tumor. (E) Follow-up axial arterial
enhanced MRI after 6 weeks shows extensive necrosis and complete response of the metastatic lesion in segment VII. (F) Follow-up axial arterial enhanced
CT scan shows no change in the complete response of the metastatic lesion in segment VII. (Courtesy Dr. Aran Chary, Emory University School of Medicine.)
D
406 TRANSARTERIAL THERAPIES FOR PRIMARY AND METASTATIC LIVER TUMORS
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is chosen when there is multifocal disease, while segmentectomy is
offered to those patients with a solitary tumor ≤5 cm and liver-only
disease when the tumor can be isolated angiographically.
Hepatic Artery Infusion
HAI chemotherapy is administered in the proper hepatic artery by a
surgically implanted pump, a hepatic arterial port, or through a percutaneously placed catheter connected to an external pump (Fig. 6).
Certain drugs with a high first-pass extraction can be delivered into
the arterial circulation with the goal of increased local concentration
of the agent, which increases the therapeutic response with decreased
systemic exposure and toxicity.
Indications and Patient Selection
1. Colon cancer
a. If surgery or ablation is not an option and there are no sys-
temic options
b. To maintain tumor size if planned surgery is significantly
delayed
2. Intrahepatic cholangiocarcinoma (ICC)
a. If systemic chemotherapy fails or in conjunction with systemic
chemotherapy
b. To target a portion of the tumor along a precarious resection
margin, thus aiding surgery
3. Neuroendocrine cancer
a. If symptomatic
b. There are clinically significant laboratory abnormalities, such
as hypoglycemia from metastatic insulinoma, or hyperglyce-
mia from metastatic glucagonoma
c. Rapid growth
d. High Ki-67 index
4. Other (pancreatic, breast, melanoma)
a. TACE for such neoplasms is less well studied and should be
tailored to each individual patient
5. Developing indications
Three novel indications are:
a. The use of preimmunotherapy TACE to bolster immune
response
b. Preoperative TACE to address micrometastasis or microvas-
cular components
c. Combined with ablation/systematic therapies for improved
outcome
Contraindications to Transarterial Chemoembolization
Major Contraindications
1. ECOG 3
2. Decompensated or borderline liver function
3. Severely reduced portal vein blood flow (acute and chronic portal
vein tumor thrombosis)
4. Extensive tumor involving the entirety of both liver lobes
5. Untreatable arteriovenous fistula
6. Renal insufficiency, including creatinine ≥2 mg/dL or creatinine
clearance <30 mL/min
7. Total bilirubin >4 or rapidly rising total bilirubin
8. Active bacterial infection
Relative Contraindications
a. Bilioenteric anastomosis or biliary stents, bile duct occlusion
2. Life expectancy <6 months
Contraindications to SIRT Application (FDA
Recommendation):
1. Prior liver irradiation
2. Coexistence of ascites and/or liver failure
3. The presence of liver dysfunction
4. The presence of metastases to organs other than the liver
5. A Capecitabine treatment in the last two months before the
surgery
6. Portal vein thrombosis
7. Pregnancy
8. Abnormal test results: WBC <2.5 thousand, Neu <1.5 thousand,
PLT <60 thousand, AST/ALT >5 × normal, bilirubin >2 mg/dL,
albumin < 3 g/dL, creatinine >2.5 mg/dL
9. Irregularities in the anatomical structure of the venous system in
the liver
Patient Preparation
1. Preprocedural fasting for 6 to 8 hours in preparation for conscious sedation or general anesthesia
2. Premedication:
a. Dexamethasone (20 mg intravenously), which reduces the
extent of postembolization syndrome
b. Proton pump inhibitors, which reduce the risk of gastri-
tis/duodenitis and mitigate the significance of nontarget
embolization
c. Hydration, which reduces fatigue, nausea
d. Antibiotics. Prophylaxis administration is necessary if the
integrity of the biliary system has been compromised by prior
biliary intubation or post-Whipple. The recommended regi-
men is moxifloxacin 400 mg by mouth daily beginning 3 days
before and continuing for 7 days postembolization.
e. Somatostatin analogs. For neuroendocrine tumors (NETs)
with a carcinoid origin. These patients are at risk of develop-
ing a carcinoid crisis during or immediately after intervention.
The ideal scheme and dosing of octreotide to prevent the
development of a carcinoid crisis have not been clearly estab-
lished and are mostly operator-dependent.
Techniques: Angiogram and Embolization Technique
1. Vascular access. Transarterial embolization can be performed
either via common femoral arterial (CFA) or radial arterial (TRA)
access. In both approaches, a 5-6 Fr vascular sheath is used. If
the radial approach is chosen, a Barbeau’s test is first performed
to minimize the risk of hand ischemia. Upon TRA access, a
cocktail of heparin and one or more vasodilators (nitroglycerin,
verapamil, or nicardipine) is administered. Administration of this
cocktail is not necessary for CFA access.
2. Diagnostic arteriograms. An angiogram is performed to:
a. Delineate the vascular anatomy related to the tumor and
assess the best treatment delivery route.
b. Map any nontarget and collateral vessels at risk for inadver-
tent chemoembolization and plan an approach to minimize
the risk. A superior mesenteric arteriogram is performed
first. This excludes replaced/collateral vascular anatomy to
the liver and shows whether the portal vein is patent or not.
Then, a celiac arteriogram is performed. This shows the target
(hepatic artery branches) and nontarget arteries (i.e., left and
right gastric artery, supraduodenal artery, cystic artery, and
umbilical artery).
3. Treatment.
a. TACE. Once the target arteries are chosen, a microcatheter is
used to obtain super-selective access. The ideal location for
the tip of the catheter is one in which an infusion from that
point would cover the entire tumor and, at the same time,
spare as much of the normal liver parenchyma as possible.
Once the catheter is in the optimum position, the treatment
mixture is delivered. Whether cTACE or DEB-TACE, this
is done under continuous fluoroscopic observation. As the
cocktail is administered, target arterioles embolize and flow
dynamics may change. cTACE is continued until stasis is
achieved and the peribiliary venous plexus is seen, while DEBTACE is stopped once substasis (slow blood flow) is noticed
on the angiogram. Overaggressive embolization may result in
antegrade reflux around the catheter and inadvertently reach
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A
B
C
D
FIG. 6 Irinotecan hepatic artery infusion for 2 days in a 34-year-old man with CRC liver metastasis. (A) Axial arterial enhancement CT shows a large
metastasis in the right hepatic lobe. (B) Angiogram demonstrates the right hepatic lobe blood supply from the right hepatic artery. The gastroduodenal artery is coiled to protect against nontarget embolization. (C) The NM study was performed using Tc99m MAA to exclude extrahepatic nontarget
chemotherapy infusion. (D) A KUB image shows the stability of the infusion catheters during the infusion period. (E) Follow-up axial arterial enhancement
CT shows the lesion has significantly decreased in size. (Courtesy Drs. Rony Avritscher, Kamran Ahrar, and Ravi Murthy from MD Anderson Cancer Center.)
E
408 TRANSARTERIAL THERAPIES FOR PRIMARY AND METASTATIC LIVER TUMORS
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nontarget organs. The organs most commonly at risk are the
duodenum, stomach, and pancreas as a result of the proximity
of their arterial supply to the hepatic artery. The technical
objective is to deliver the entire treatment mixture into the
target tumor and reach blood flow stasis within the artery that
supplies it. Additional particle use may be necessary to achieve
stasis. If multiple tumors are targeted, it is best to target each
individual tumor as selectively as possible, as opposed to
treating an entire lobe. Although more time-consuming and
technically challenging, selective embolization carries a lesser
risk of liver injury and results in a better response.
If lipiodol is used in the TACE mixture, intraprocedural cone-
beam CT or noncontrast computed tomography can be
obtained after the procedure to assess the extent of lipiodol
deposition (Fig. 3C), which reflects the treated area.
Note that, in general, only one lobe (right or left) can be
treated at any one time because TACE results in transient
liver enzymes elevation, with the treated liver recovering
by approximately 2 weeks. During the recovery period,
adequate remaining liver function must be ensured. In
cases in which multiple subselective TACEs can be performed without affecting a significant portion of the
normal liver parenchyma, bilateral disease can be treated
in one session.
b. SIRT. Patients undergo a diagnostic angiogram, as described
earlier, followed by technetium-99m macroaggregated albumin (Tc-99m MAA) shunt study approximately 2 weeks
before SIRT (Fig. 4C). Approximately 4 mCi of Tc-99 m
MAA is administered, either into the common hepatic artery
or into right and left hepatic arteries in a split-dose fashion
depending on the distribution of the tumor. The selection of
the proper supply artery to the targeted tumors from a specific
microcatheter position is ascertained with cone-beam CT
if segmentectomy is pursued. After the injection of Tc-99m
MAA and termination of the angiogram, the patient is transferred to the nuclear medicine department for SPECT/CT
to assess any possible shunt (specifically lung shunt) and to
ensure the proper deposition of Tc-99m MAA in the targeted
area. The dose of
90
Y to be administered is calculated using
different models depending on the disease, microparticle of
choice, and the operator’s preference, such as the Partition
model, the MIRD model, or the body BSA model. On the
day of treatment,
90
Y is administered from the same position where Tc-99m MAA was injected for the shunt study.
If patient requires bilobar treatment, the hepatic lobe with
the larger disease burden is treated first, then the remaining
lobe is treated 4 to 6 weeks following the initial treatment.
90
Y
SPECT/CT is obtained immediately following SIRT for each
patient (Fig. 4D and Fig. 5D). Liver volume, tumor volume,
and the corresponding radioactive counts are then calculated
manually and using the software-generated dose-volume
histograms.
c. HAI. The Seldinger technique is used percutaneously to
reach the hepatic artery and place infusion catheters. The left
subclavian and femoral artery represent the most frequent
peripheral accesses, although the hypogastric, subclavian,
and brachial arteries have all been used as well. The common
femoral arterial access is technically easier as the vessel is
superficial and less tortuous. There are several techniques
used for the placement of the tip of the catheter, such as the
“fixed-catheter-tip” technique, where the distal tip of the catheter has been fixed to the gastroduodenal artery, whereas the
injected drug flows into the proper hepatic artery through a
side hole, or the “long tapered catheter placement” technique,
in which the catheter is positioned, but not fixed, as distally
as possible into the common hepatic artery with the side hole
placed at the origin of the proper hepatic artery.
4. End of procedure. Once the technical objective is reached, the
catheters and sheath are removed, and depending on the access
site, TRA, or CFA, hemostasis is secured. The latter can be
achieved by either a 15-minute manual compression or by the
use of a vascular closure device. The use of any closure devices for
CFA access obviates the need for manual pressure and allows the
patient to ambulate after 2 hours rather than 4 hours. However,
the patient could ambulate right away after the procedure if TRA
access was used.
5. Patient recovery. Patient recovery is centered around symptom
prevention and control, and requires approximately 24 hours.
Postprocedural hydration, as-needed antiemetics and stool softener, and pain control are the mainstay of recovery. In patients
with severe abdominal pain, a patient-controlled analgesia pump
is very beneficial. Postchemoembolization syndrome is the most
common set of symptoms, reported in at least in 60% of patients,
and includes fatigue, fever, and abdominal pain. These symptoms
gradually subside over approximately 2 weeks. Other symptoms
that could be encountered include nausea, anorexia, and more
rarely, alopecia (4%) and night sweats. The volume of embolization and the degree of tumor necrosis have been correlated with
the severity of symptoms.
POSTPROCEDURE FOLLOW-UP
Regardless of the transarterial approach method (BE, cTACE, DEBTACE, or SIRT), the follow-up protocol is usually the same. It includes
a repeat multiphasic MRI with intravenous gadolinium-based contrast or a multiphasic CT of the abdomen with intravenous iodinebased contrast, laboratory tests (comprehensive metabolic panel,
complete blood count, international normalized ratio, relevant
tumor markers), and a clinic visit to reassess the patient’s performance status. Follow-up is generally at 1 month and then 3-month
intervals, but this must be tailored to each patient and according to
treatment goals. The first follow-up cross-sectional images are commonly obtained 1.5 to 2 months after SIRT to differentiate post-SIRT
inflammatory changes from residual disease.
There is no limit to the number of TACE treatments a patient
can receive. Further treatment should be aborted, however, if any
contraindications develop (please refer to the earlier list), if the initial
indication is no longer valid, or if, after three cTACE treatments, the
targeted lesion fails to respond as expected. Studies have shown that
failure of the initial two cTACE treatments does not predict failure of
the third treatment; however, if three TACE treatments fail to result
in tumor response, additional treatment is unlikely to have any benefit. Also, the number of SIRT sessions is limited by the lung dose of
no more than 30 Gy in a single SIRT session or no more than 50 Gy
in multiple SIRT sessions.
TOXICITIES AND COMPLICATIONS
Complications related to embolization are summarized in Table 1.
A majority of patients (>60%) will have the described postembolization syndrome. It is always self-limiting and only symptomatic care
is indicated. The most serious complication is acute liver decompensation resulting from embolization-related acute liver injury.
The related risk is small (<1%) and only considered when there is
underlying liver disease (cirrhosis, severe steatohepatitis, significant
history of systemic chemotherapy). However, unilateral TACE all but
eliminates this risk in cases of metastatic disease. Another concern
is developing encephalopathy, which is also unlikely since TACE for
secondary liver disease is usually performed in patients with intact
liver function. A previous history of encephalopathy is the major risk
factor for worsening encephalopathy. Both acute liver failure and the
risk of encephalopathy can be further mitigated by subselective treatments. Another concern is biliary complications, including stricture
and abscess formation. The biliary tree is known to be supplied by
the hepatic artery. Therefore, overzealous embolization (especially
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