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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_3869_Библиотеки_им_академика_М_И_Перельмана.pdf
186 J. Patel
a
c
Fig. 19.1 MRI—most commonly mass with decreased signal on T1W, moderately increased
signal on T2W (a), lack of uptake of super-paramagnetic iron oxide (SPIO) (b), arterial-phase
enhancement with gadolinium (c), and washout in the portal phase (d)
b
d
• MRI—mass with decreased signal on T1W, moderately increased signal on
T2W, lack of uptake of super-paramagnetic iron oxide (SPIO), arterial-phase
enhancement with gadolinium and washout in the portal phase (Fig. 19.1).
Differential Diagnosis Includes
• Dysplastic nodules—these require differentiation from HCC in patients with
underlying cirrhosis (look for lack of uptake of SPIO and absence of washout
in the portal phase).
• Other benign hypervascular lesions, e.g., focal nodular hyperplasia, hemangioma,
adenoma (although most of these will have their own specific imaging features).
Laboratory/Other Investigations
• Define the degree of liver dysfunction (LFTs, prothrombin time, AFP). This is
important in any form of therapy that might adversely affect function.
19 Liver Tumors (Hepatocellular Cancer) 187
• Assess renal function as there is potential for nephrotoxicity from contrast and
chemotherapeutic agents.
• Assess left ventricular ejection fraction if using cardiotoxic drugs, e.g.,
doxorubicin.
General Considerations
Transarterial chemoembolization (TACE) should currently be considered as palliative and not curative. Indications for TACE will vary from institution to institution.
TACE is currently indicated for intermediate stage HCC (i.e. patients unsuitable
for potentially curative surgical resection, liver transplantation or local ablative
therapies) with relatively well-preserved liver function. TACE may also be of value
in combination therapy for downstaging focal lesions which are just beyond the size
limits for local ablative therapies or as a bridge to transplantation.
Prognosis is affected by both the stage of the tumor and the degree of liver dysfunction at the time of presentation. A number of scoring/staging systems have been
developed for prognostic and management purposes (Okuda, Cancer of the Liver
Italian Program—CLIP, Barcelona Clinic Liver Cancer—BCLC these include factors such as tumor size, Child-Pugh score, AFP level, presence of vascular invasion,
performance status, etc.
Contraindications
No absolute contraindications, but relative contraindications include the following:
• Child-Pugh score ≥ 8
• Bilirubin > 50 μmol/L
• Portal vein (PV) thrombosis (arterial embolization will lead to infarction)
• Hepatofugal PV flow (increased risk of infarction)
• Large-volume tumors (occupying >50% of liver mass)
• Extrahepatic disease
Pre-procedure Evaluation
• Review previous imaging and laboratory results to assess suitability for TACE.
• Determine number, distribution and vascularity of lesions, patency of PV,
presence of extrahepatic disease.
• Identify factors that will influence approach or complexity of procedure, e.g.,
morphology of celiac axis, variant arterial anatomy, arterial stenosis.
• Decide whether selective or lobar embolization is appropriate.
188 J. Patel
Anatomic Considerations
Normal Anatomy
• Normal liver supplied by portal vein (PV) = 75% and hepatic artery (HA) =
25%.
• HCC supplied by HA = 90% and PV = 10%.
HA divides into right and left branches; right HA artery sub-divides further into
anterior and posterior branches supplying segments 5/8 and 6/7, respectively.
This “normal” arrangement is seen in approximately 50% patients.
• Cystic artery usually arises from the proximal right HA.
• Right gastric artery may also arise from the right HA.
Variant Anatomy: (See also Table 33.1) (Fig. 19.2)
Considerable variability in the anatomy of the hepatic artery exists.
Commonest variants are as follows:
• Replaced (14%) or accessory (6%) right HA arising from superior mesenteric
artery
• Replaced (12%) or accessory (8%) left HA arising from the left gastric artery
• Proper hepatic artery arising from the superior mesenteric artery (2.5%).
Fig. 19.2 (a) Replaced right hepatic artery arising from the superior mesenteric artery. (b)Theleft
hepatic artery arises from the common hepatic artery
Extra-hepatic Supply (Fig. 19.3)
Liver tumors may have additional supply from non-hepatic vessels depending on
their location (e.g., tumors located in the dome of the liver may be partly supplied
19 Liver Tumors (Hepatocellular Cancer) 189
Fig. 19.3 (a) Large hepatoma supplied predominantly from the right hepatic artery. (b)The
superomedial aspect of the tumor is supplied by the right inferior phrenic artery
by the right internal mammary artery when located anteriorly or by the inferior
phrenic artery when located posteriorly).
Consent
Important things to explain to the patient during consent are as follows:
• TACE is a palliative procedure and not curative.
• Approximately 50% increase in survival at 2 years compared to conservative
therapy.
• Post-embolization syndrome (pain, sickness, flu-like symptoms) is common.
• General feeling of fatigue (usually lasting 2 weeks).
• Complications:
◦ Puncture site (<5%)—hematoma, bleeding, thrombosis.
◦ Treatment related (1–5%)—infection/abscess, acute liver failure, neutropenia.
Equipment
Catheters
• 4-French sidewinder or cobra catheter (dependent on personal preference) to
catheterize celiac axis and hepatic artery.
• Coaxial microcatheter for selective catheterization of segmental vessels as
necessary.
• Remember to use catheters without sideholes.
190 J. Patel
Chemotherapeutic Agents
• Drugs have to be ordered in advance and in accordance with hospital regulations.
• Cisplatin, doxorubicin, mitomycin C or a combination of these have been used.
• There is no absolute evidence for the superiority of any particular agent.
• All staff in the angio room should wear protective masks and visors while
handling cytotoxic drugs.
Embolic Agent
Lipiodol
• Drug carrier and partial embolic agent
• Used to create an emulsion with the chemotherapeutic agent prior to infusion into
the catheter
Particulate Agents
• Polyvinyl alcohol (PVA)
• Gelfoam
Drug-Eluting Beads
• DC/LC Beads (Biocompatibles UK Ltd) and Hepasphere/Quadrasphere
(Biosphere Medical, Rockland, MA, USA) are the main agents.
• Function as both the drug carrier and embolic agent.
• Embolic microspheres loaded with chemotherapeutic agent (usually doxoru-
bicin).
• Subsequent drug elution gives a more sustained concentration of drug within the
tumor and much reduced systemic concentration compared with lipiodol-based
treatment.
• Only suitable for patients in whom selective TACE (right or left lobe) can be
performed.
• Hepasphere/Quadrasphere is slightly different to DC Beads in that they swell
within several minutes after contact with aqueous solutions, blocking the
embolized artery.
• These are exciting developments in localized chemoembolization of HCC and
results are promising.
Bland Embolization Versus TACE
• Note that controversy exists between bland embolization and embolization with
chemotherapeutic agents.
• The endpoint of bland embolization is cessation of flow to the tumor and
consequent ischemia; this is a different endpoint to TACE.
19 Liver Tumors (Hepatocellular Cancer) 191
• However, most IRs continue to use a chemotherapeutic agent as part of TACE,
although there is no level-1 evidence to support either approach.
Radioembolization
• Embolization using radioactive particles containing usually yttrium-90.
• Main agents are Therasphere (MDS, Nordion, Canada) and SIR spheres (Sirtex,
Sydney, Australia).
• Yttrium-90 is a beta-emitter that irradiates tissue with path length of 2.5 mm
(maximum 10 mm) and half-life of 64.2 h.
• Theraspheres are glass yttrium-90 beads and SIR spheres are resin beads
containing yttrium-90.
• The technique is much more involved than TACE with embolization of all extra-
hepatic collaterals required (“skeletonizing the hepatic artery”) and technetium
scanning to exclude shunting to the lung beforehand.
• More results from this exciting technology are awaited.
Selective Versus Non-selective TACE
Perform TACE as selectively as possible to reduce post-embolization syndrome and
complications. As general principles
• Superselective/sub-segmental—if focal lesion ≤5 cm or up to three lesions
≤3cm.
• Selective/segmental—if large lesion or several lesions confined to one or two
segments.
• Non-selective/lobar—if multifocal lesions scattered diffusely.
• Consider dividing into two to three treatment sessions (right anterior, right
posterior, and left lobe) to reduce the risk of significant liver dysfunction.
• Remember to place catheter beyond the cystic artery and/or right gastric artery
origins to prevent embolization of the gallbladder or stomach.
Leave 4 weeks between treatment sessions to allow for recovery of liver function.
Procedure
Pre-procedure Preparation
• Fast patient for 4 h (allow clear fluids).
• Ensure hydration: clear fluids and intravenous (IV) hydration.
• IV broad-spectrum antibiotics (e.g., cefuroxime and metronidazole).
• Opiate analgesia—consider patient-controlled analgesia as it is often easier to
manage pain control with this, once the patient returns to the ward.
• Antiemetic—nausea can originate from both the opiate analgesia and post-
embolization syndrome.
192 J. Patel
Access
• Femoral artery access is usual.
• Brachial artery access may occasionally be required in cases of difficult anatomy
or severe atherosclerotic disease of the iliac arteries.
Initial Diagnostic Study
• Start with angiography of the celiac axis ± superior mesenteric artery.
• Inject 24 ml at 6 ml/second.
• Start imaging at two frames per second for the arterial phase, reducing to one
frame per second for the portal phase.
• Consider 8 s injection delay to allow for multimasking.
• Identify any variants in the vascular anatomy.
• Confirm patency/direction of flow in the portal vein.
Selective Angiography
After non-selective angiography, specific feeding segmental arteries can be selected.
• 20 ml at 4 ml/s, 2 s injection delay; two frames/s, arterial and parenchymal phase.
• Projection: AP ± oblique views.
• Localize lesions and identify vessels feeding the tumor.
• The tumor supply will show neovascularity (tortuous vessels with abnormal
branching pattern), vascular lakes, arterio-portal or arterio-venous shunting,
localized parenchymal blush (Fig. 19.4).
Fig. 19.4 Hepatic angiography showing typical features of hepatoma (a) arterial phase with
abnormal vessels, venous lakes (b) late phase showing peripheral parenchymal enhancement
19 Liver Tumors (Hepatocellular Cancer) 193
Catheterize the feeding vessel with a co-axial microcatheter.
• Confirm position with angiography.
• Either, hand injection using a 2–3 mL syringe, or pump injection (6 mL at a
maximum of 3 mL/s, maximum 700 psi pressure).
Perform Chemoembolization
Technique: Lipiodol
• Form emulsion of cytotoxic drug and lipiodol by passing between two syringes
connected via a three-way tap (Fig. 19.5).
• Infuse through microcatheter until forward flow slows. If necessary, follow lip-
iodol infusion with particulate embolization using either PVA 300–500 μm
particles or gelfoam.
• The maximum dose of chemotherapeutic agent is limited per session.
Fig. 19.5 Technique for
mixing lipiodol and cisplatin
using two syringes and a
three-way tap. The mixture is
forced back and forth until it
becomes an emulsion at
which point there is a notable
drop in resistance
Technique: Drug-Eluting Beads
• DC beads are loaded with doxorubicin in pharmacy and mixed with contrast sev-
eral hours pre-procedure. For Hepaspheres, doxorubicin is mixed with 10 mL of
normal saline and left to stand for 1 h before use.
• Inject down the microcatheter like any other particulate embolic agent until
forward flow slows and peripheral side-branch vessels are pruned.
Endpoints: Two Procedural Endpoints Should be Considered
1. Forward flow slows and no further chemoembolic agent can be given without
producing non-target embolization.
194 J. Patel
2. All the chemoembolic agent has been given—consider finishing off with bland
particulate embolization or, if there is still significant tumour vascularity,
repeating the procedure after a 1-month interval.
Post-procedure
• Remove catheter and achieve hemostasis.
• Reiterate the importance of symptomatic management of post-embolization
syndrome to the ward staff and patient.
• Explain the symptoms/signs of delayed infection to the patient (increasing pain
and/or pyrexia) and the importance of seeking prompt medical review.
• Patient can usually be discharged at 24–48 h post-procedure.
• Check liver function, prothrombin time, and renal function prior to discharge and
repeat again 1 week prior to any further planned treatment.
• Check clinical status of the patient prior to repeat treatment.
Post-procedure Follow-Up
Once there is no residual tumor vascularity on completion angiography or after 3
treatment sessions, re-evaluate the patient with follow-up imaging after 4–6 weeks.
RECIST criteria or EASL criteria used for follow-up.
Assess
• Tumor volume
• Amount of lipiodol retention
• Residual viable (enhancing) tumor
• Disease progression: increase in size or enhancement, new lesions, spread to
other organs, portal vein thrombosis
Consider further treatment if imaging shows residual tumor enhancement.
Keypoints
• TACE is a palliative procedure for intermediate-stage HCC and early-stage
disease unsuitable for potentially curative treatment.
• It is important to select patients carefully, based on both tumor morphology
and liver function as both these have prognostic implications for patient
survival.
19 Liver Tumors (Hepatocellular Cancer) 195
• Treat as selectively as possible to minimize side-effects and complications,
especially if patients are in Child-Pugh class B.
• Avoid non-target chemoembolization to the gallbladder or stomach.
• If considering a repeat procedure, ensure that the patient has recovered
both clinically and biochemically following the preceding procedure.
• Results of DC-bead/LC bead studies and radioembolization studies are
awaited.
• In future, combinations of therapies with Sorafenib may be very
promising.
Suggested Reading
Llovet JM, Bruix J. Systematic review of randomised trials for unresectable hepatocellular
carcinoma: chemoembolization improves survival. Hepatology 2003; 37:429–42.
Kettenbach J, Stadler A, Katzler I, Schernthaner R, Blum M, Lammer J, Rand T. Drug-loaded
microspheres for the treatment of liver cancer: review of current results. Cardiovasc Intervent
Radiol 2008; 31:468–76.
Lee KH, Sung KB, Lee DY, Park SJ, Kim KW, Yu JS. Chemoembolization for hepatocellular
carcinoma: anatomic and haemodynamic considerations in the hepatic artery and portal vein.
RadioGraphics 2002; 22:1077–91.
Kim CH, Chung JW, Lee W, Jae HJ, Park JH. Recognising extrahepatic collaterals vessels that
supply hepatocellular carcinoma to avoid complications of transcatheter arterial chemoembolization. RadioGraphics 2005; 25:S25–39.
Clark HP, Carson WF, Kavanagh PV, Ho CPH, Shen P, Zagoria RJ. Staging and current treatment
of hepatocellular carcinoma. RadioGraphics 2005; 25:S3–23.