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  1. 1. Percutaneous Ablation of HepatocellularCarcinoma: Current StatusJustin P. McWilliams, MD, Shota Yamamoto, BS, Steven S. Raman, MD, Christopher T. Loh, MD, Edward W. Lee, MD, David M. Liu, MD, and Stephen T. Kee, MDHepatocellular carcinoma (HCC) is an increasingly common disease with dismal long-term survival. Percutaneousablation has gained popularity as a minimally invasive, potentially curative therapy for HCC in nonoperativecandidates. The seminal technique of percutaneous ethanol injection has been largely supplanted by newer modal-ities, including radiofrequency ablation, microwave ablation, cryoablation, and high-intensity focused ultrasoundablation. A review of these modalities, including technical success, survival rates, and complications, will bepresented, as well as considerations for treatment planning and follow-up.J Vasc Interv Radiol 2010; 21:S204 –S213Abbreviations: HCC ϭ hepatocellular carcinoma, PEI ϭ percutaneous ethanol injection, RF ϭ radiofrequencyHEPATOCELLULAR carcinoma (HCC) During the past few decades, several all patients to define the size and numberis now the fifth most common cancer, minimally invasive ablation techniques of tumors, their location, and their rela-and the third leading cause of cancer have been developed to prolong the “sur- tionship to vital structures.death worldwide (1). Although hepatic vivability” of unresectable HCC. Percuta- At our institution, treatment decisionsresection remains a first-line treatment, neous ethanol injection was introduced as for hepatocellular carcinoma are made inapproximately 80% of patients are not the seminal ablation technique for HCC in the setting of a multidisciplinary tumorcandidates as a result of poor hepatic the 1980s. In 1990, the first use of percuta- board, including representatives from on-reserve, tumor location, or tumor bur- neous radiofrequency (RF) ablation for cology, hepatology, abdominal and inter-den (2), and eventual tumor recurrence HCC was published (7), followed by per- ventional radiology, surgery, and radia-is the rule (3). Orthotopic liver trans- cutaneous microwave (MW) ablation in tion oncology. Percutaneous ablation isplantation offers high rates of disease- 1994 (8). More recently, cold-based and the preferred mode of treatment for non-free remission (4), but is limited by strin- extracorporeal techniques have also been surgical candidates with one or severalgent selection criteria, cost, and donor introduced (Fig). Ablation can offer po- tumors up to 3 cm, or up to 5 cm in selectavailability (5). Overall 5-year survival tentially curative treatment for small (Ͻ 3 situations. Once referred for ablative ther-rates for HCC remain lower than 10% in cm) and medium-sized (3–5 cm) HCC, apy, all patients are seen in clinic with theEurope and the United States (6). can salvage cases of tumor recurrence, interventionist, at which time a history and can “bridge” patients to orthotopic and physical is performed, the risks and liver transplantation by prolonging sur- benefits of the procedure are discussed, vivability and decreasing tumor burden and visibility of the tumor on ultrasoundFrom the Departments of Interventional Radiology(J.P.M., C.T.L., D.M.L., S.T.K.) and Radiological Sci- (9–12). is confirmed.ences (S.Y., E.W.L.), University of California Los In this review, we discuss the percuta- Durable success of ablation, and re-Angeles Medical Center, 757 Westwood Plaza, Suite neous ablative therapies for local control sultant improved survival, depends on2125C, Los Angeles, CA 90095; Department of Radi- of HCC, with a focus on survival data, complete ablation of the tumor (13,14).ology, Faculty of Medicine (D.M.L.), University of recurrence rates, and complications.British Columbia; and Department of Radiology, The likelihood of complete ablation de-Interventional Radiology Section (D.M.L.), Van- creases with increasing tumor size (14 –couver General Hospital, Vancouver, British Co- 16), and multiplicity of tumors com-lumbia, Canada. Received October 7, 2009; final TREATMENT PLANNING pounds this consideration. Transarterialrevision received October 28, 2009; accepted No-vember 7, 2009. Address correspondence to J.P.M.; The use of biomarkers and surveil- chemoembolization, systemic chemo-E-mail: lance imaging with ultrasound (US), com- therapy, or symptomatic treatment can puted tomography (CT), and magnetic be considered if the tumor burden isNone of the authors have identified a conflict ofinterest. resonance (MR) imaging has facilitated deemed excessive or unsafe for ablation. the early detection of HCC (12). Mul- The approach to the tumor should© SIR, 2010 tiphase contrast-enhanced CT or MR im- avoid crossing other organs, large vessels,DOI: 10.1016/j.jvir.2009.11.025 aging of the liver should be performed in and major bile ducts. With the use of US,S204
  2. 2. Volume 21 Number 8S McWilliams et al • S205 RF Ablation RF ablation uses rapidly alternating RF current to induce frictional heat around an electrode, producing cell death by coagulation necrosis. Small electrode diameter, good ablation area size, and effective marketing have com- bined to make RF ablation a popular technique. RF ablation also benefits from the “oven effect”; heat retention is improved in lesions surrounded by cir- rhotic tissue (35). Complete ablation rates for small to medium HCC exceed 80% in a single treatment session, and exceed 90% with two sessions; 5-year survival rates in the largest studies are 40%–58% (14,18,19,36 –39). Local pro- gression after complete ablation is un- commonly observed (1%–12%). RF abla- tion studies are summarized in Table 1 (18,19,36 –38).Figure. Representative percutaneous ablation devices. Clockwise from top left: Cool-Tip The most commonly used RF abla-internally cooled RF electrode, LeVeen expandable RF electrodes, Evident 915-MHz tion devices in contemporary practicecooled-shaft percutaneous MW antenna, and Perc-24 cryoprobe (Endocare, Irvine, Cali- are monopolar internally cooledfornia). (Available in color online at electrodes, such as the Cool-Tip de- vice (Covidien, Mansfield, Massa- chusetts), and monopolar multitinedsome obliquity can usually be found that ous ethanol injection (PEI). Several non- expandable electrodes, such as thewill allow safe placement of the ablation randomized trials in the 1990s (25–27) LeVeen (Boston Scientific, Natick, Mas-probe. CT-ultrasound fusion imaging, confirmed that PEI can safely achieve sachusetts) or RITA (Angiodynamics,which matches a preprocedural volumet- complete necrosis of small HCCs, with Queensbury, New York) devices. Tworic CT to real-time ultrasound images, can 5-year survival rates of 32%–38%. How- studies have been performed compar-aid probe placement in difficult cases (17). ever, the technique suffered from the need ing the effectiveness of the two electrodePositioning of the active tip near the large for multiple treatment sessions, uncer- types in the treatment of small HCCand small bowel, bile ducts, stomach, gall- tainty of the ablation zone, and a high (40,41); neither study found any differ-bladder, and diaphragm can cause collat- local progression rate of 17%–38% (28,29). ence in immediate treatment success,eral damage and limits percutaneous ab- Several randomized controlled trials complication rate, local progression, orlation in approximately 6–9% of cases compared PEI versus RF ablation in the overall survival between the treatment(18,19). treatment of small HCC (30–32). These groups (40,41). In such cases, adjunctive use of dex- Cohort studies of RF ablation have trials demonstrated an approximatelytrose solution (20), carbon dioxide shown low rates of major complications, 20% advantage for RF ablation versus PEI(21), or balloon interposition (22) can ranging from 0.9% to 5.0%. (37,42). Peri- in overall survival at 3–4 years, mainly asseparate and protect vital organs. toneal hemorrhage, bile duct injury, ab- a result of a much lower incidence of local scess, and intestinal perforation wereThermocouples can be used to moni- tumor recurrence in the RF ablation the most notable adverse outcomes.tor temperatures adjacent to sensitive group. Also, approximately threefold Tumor seeding is occasionally re-structures (23). For lesions adjacent tomain bile ducts, the placement of a fewer treatment sessions were required ported, particularly with subcapsularnasobiliary stent with instillation of for RF ablation compared with PEI. Two tumors, but rarely occurs when carefulchilled saline can protect the ducts recent metaanalyses comparing RF abla- attention is given to technique (indi-from thermal damage (24). These tech- tion versus PEI echoed these sentiments, rect tumor puncture, gradual increaseniques allow the vast majority of abla- declaring RF ablation superior to PEI in in power deposition, and thermocoag-tions to be safely and effectively per- the treatment of small HCC (33,34). ulation of the needle track) (43).formed using percutaneous technique. PEI maintains the advantage of al- RF ablation does have some disad- lowing treatment of tumors near sensi- vantages. The majority of ablation oc- tive organs and tissues, and avoids the curs through thermal conduction, whichHCC TREATMENT problem of the “heat-sink” effect adja- can be limited by tissue desiccation andMODALITIES cent to vessels. The applicability of PEI charring (44). RF ablation is susceptiblePercutaneous Ethanol Injection in other situations is limited. Given the to a heat-sink effect from flowing blood, superiority of RF ablation to PEI for the which may result in sublethal tempera- One of the first methods devised to treatment of HCC, this review will focus tures adjacent to vessels larger than 3ablate liver tumors involved percutane- on thermal ablation. mm in size (45– 48). As a result of elec-
  3. 3. S206 • Percutaneous Ablation of HCC August 2010 JVIR Table 1 Percutaneous RF Ablation in de novo HCC among Cohort Studies with at Least 100 Patients and 5-year Survival Data (18,19,36 –38) Tumor Size Survival (cm) Complete (%) Local Major No. of Child Class Ablation No. of Recurrence Complications Study, Year Pts. (A/B/C) Mean Range (%) Sessions 3y 5y (%) (%) Lencioni et al, 2005 (18) 187 144/43/0 2.8 1.5–5.0 90 1.2† 71 48 10 2 N’Kontchou et al, 235 205/30/0 2.9 1.1–5.0 94 1.2† 60 40 12 0.9 2005 (36) Tateishi et al, 2005 (37) 319* 221/94/4 2.6 0.8–9.7 93 1–2 78 54 2 4 Raut et al, 2005 (38) 140 59/46/35 3.0 NR 97 1 74 58 3 5 Livraghi et al, 2008 (19) 218 218/0/0 NR Յ2 98 1.1† 76 55 1 2 Note.—NR ϭ not reported. * A total of 137 of these patients received transarterial embolization before RF ablation. Tumor size, technical success rate, local recurrence rate, and major complication rate are composite data from de novo and recurrent HCC in this series. † Mean. Table 2 Details of Percutaneous Microwave Ablation in HCC among Cohort Studies with at Least 50 Patients (51–53) Survival Tumor Size (cm) Complete (%) Local Major No. of Child Class Ablation Recurrence Complications Study, Year Pts. (A/B/C) Mean Range (%) 3y 5y (%) (%) Dong et al, 2003 (51) 234 24/207/3 4.1 1.2–8.0 89* 66 57 7% 0% Liang et al, 2005 (52) 288 54/214/20 3.8 1.2–8.0 NR 72 51 8% NR Lu et al, 2001 (53) 50 16/30/4 2.7 0.8–6.4 94† 73 — 6% 0% Note.—NR ϭ not reported. * One session. † Two sessions.tromagnetic interference, only one RF nae can be simultaneously activated series showed no difference in completeelectrode can be activated at one time, with MW ablation, potentially allowing ablation rate or survival between thewhich can lengthen procedure time in more rapid treatment of large or multi- two techniques in HCC averaging 2.6medium and large lesions. Finally, the focal tumors (50). Grounding pads are cm in size, despite worse underlyinggrounding pads required for RF abla- not required. liver disease and more tumor multiplic-tion can occasionally cause skin burns. Three cohort studies of percutaneous ity in the MW ablation group (55). InThese limitations have invited interest MW ablation in a mix of small to large contrast, a second unmatched seriesin alternative ablation modalities de- HCC demonstrated a complete ablation in small HCC showed better survival inscribed in the subsequent sections. rate of 89%–94%, local progression rate the RF ablation group (71% vs 49% at 3 of 6%– 8%, and 5-year survival rate of years), largely due to higher complica-Microwave Ablation 51%–57%, despite a predominance of tion and local recurrence rates with MW patients with Child class B disease (51– ablation (56). Microwave (MW) ablation uses high- 53). These results compare favorably The range of complications encoun-frequency electromagnetic energy to ag- with the results of RF ablation (Table 2) tered with MW ablation are the same asitate water molecules, producing frictional (51–53). with RF ablation, including hemor-heat and resultant coagulation necrosis. One randomized controlled trial (54) rhage, abscess, biliary tract injury, andAlthough both modalities function by compared MW ablation versus RF abla- tumor seeding. The rate of major com-tissue heating, MW ablation has several tion for small HCC in 72 well matched plication in most series varies from 0%advantages versus RF ablation. MW ab- patients. The complete ablation rates to 8%, similar to RF ablation.lation has a much broader zone of active were similar (89% for MW and 96% for The above-quoted studies of percuta-heating, leading to higher temperatures RF). Long-term survival was not re- neous MW ablation come from Asia, us-within the targeted zone in a shorter ported. ing a previous-generation 2450-MHztreatment time. The active heating of The only comparative survival data microwave system. A new generation ofMW ablation is less affected by the heat- for MW versus RF ablation with percu- cooled-shaft 2450-MHz antennae prom-sink effect, improving tumor necrosis taneous technique come from retrospec- ise ablation volumes similar to the lat-adjacent to vessels (49). Multiple anten- tive, unmatched case series. One such est-generation RF ablation electrodes