There is no universal algorithm implemented. Percutaneous Ablation of Hepatocellular Carcinoma: State-of-the-Art

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1 Percutaneous Ablation of Hepatocellular Carcinoma: State-of-the-Art Riccardo Lencioni, Dania Cioni, Laura Crocetti, and Carlo Bartolozzi Percutaneous ablation is considered the best treatment option for patients with early-stage hepatocellular carcinoma (HCC) who are not candidates for surgical resection or liver transplantation. Several methods have been developed, including intratumoral injection of ethanol or acetic acid, and thermal ablation with radiofrequency, laser, microwaves, or cryosurgery. Percutaneous ethanol injection (PEI) has been the most widely used technique. Several series have provided indirect evidence that PEI improves the natural history of HCC. Patients with Child- Pugh class A cirrhosis and either a single tumor smaller than 5 cm or as many as three lesions each smaller than 3 cm may achieve a 5-year survival of 50%. The major limitation of PEI is the high local recurrence rate, which may reach 33 43%. Radiofrequency (RF) ablation has emerged as the most powerful alternate method for percutaneous ablation. Recent studies have shown that RF ablation can achieve more effective local tumor control than PEI with fewer treatment sessions. In a randomized trial, local recurrence-free survival rates were significantly higher in patients who received RF ablation than in those treated by PEI, and treatment allocation was confirmed as an independent prognostic factor by multivariate analysis. RF ablation could therefore be considered as the percutaneous treatment of choice for patients with early-stage tumors. Further investigation is warranted to clarify whether current RF technology could offer improved results in patients with intermediate-stage HCC. (Liver Transpl 2004;10:S91 S97.) There is no universal algorithm implemented worldwide for the treatment of hepatocellular carcinoma (HCC) in cirrhosis. 1 If diagnosed at an early stage, patients should be considered for any of the available options that may provide a high rate of complete response. These include surgical resection, liver transplantation, and percutaneous techniques of tumor ablation. 1 Indication for surgical resection is currently restricted to patients with single asymptomatic HCC and extremely well-preserved liver function, that have neither clinically significant portal hypertension nor abnormal bilirubin. 2,3 Cadaveric liver transplantation is limited by the shortage of donors and living donor liver transplantation is still at an early stage of clinical application. 2,3 As a result, percutaneous ablation plays a key role in the therapeutic management of HCC. While ethanol injection is a well-established technique for percutaneous ablation, several newer methods of tumor destruction have been developed and clinically tested over the past few years. Among these methods, radiofrequency (RF) thermal ablation constitutes the most extensively studied alternative to ethanol injection. 4 General Eligibility Criteria A careful clinical, laboratory, and imaging assessment has to be performed on each individual patient by a multidisciplinary team to evaluate eligibility for percutaneous ablation. Patients classified as stage A according to the Barcelona Clinic Liver Cancer staging classification, which are not candidates for surgery, qualify for percutaneous ablation. 5 The tumor to treat by RF must be a focal, nodular-type lesion. The presence of a clear and easy-to-detect target for needle placement is crucial for the outcome of treatment. Tumor size should be preferentially smaller than 3 5 cm in greatest dimension. When using thermal methods of tissue destruction, some additional points have to be considered. Treatment of lesions adjacent to the gallbladder or to the hepatic hilum risks thermal injury of the biliary tract. Lesions located along the surface of the liver can be considered for thermal ablation, although their treatment requires experienced hands and may be associated with a higher risk of complications. A careful assessment of the coagulation status is mandatory before percutaneous ablation. A prothrombin time ratio (normal time/patient s time) greater than 50% as well as a platelet count higher than 50,000/ l are required to keep the risk of bleeding at an acceptable low level. Percutaneous Ethanol Injection Percutaneous ethanol injection (PEI) is a well-established technique for tumor ablation. 6 PEI induces local Abbreviations: HCC, hepatocellular carcinoma; PEI, percutaneous ethanol injection; RF, radiofrequency; MCT, microwave coagulation therapy; PCS, percutaneous cryosurgery. Division of Diagnostic and Interventional Radiology, Department of Oncology, Transplants, and Advanced Technologies in Medicine, University of Pisa, Italy Address reprint requests to Prof. Riccardo Lencioni, Diagnostic and Interventional Radiology, University of Pisa, Via Roma 67, I Pisa, Italy. Telephone: ; Fax: ; Lencioni@med.unipi.it Copyright 2004 by the American Association for the Study of Liver Diseases Published online in Wiley InterScience ( DOI /lt Liver Transplantation, Vol 10, No 2, Suppl 1 (February), 2004: pp S91 S97 S91

2 S92 Lencioni et al Table 1. Survival Rates of Patients With Small Hepatocellular Carcinoma Treated With Percutaneous Ablation* Survival Rates (%) Trial Year Type of Study No. Patients Treatment Method 1-yr 3-yr 5-yr Castells et al Prospective 30 PEI N/A Lencioni et al Prospective 105 PEI Livraghi et al Retrospective 293 PEI Yamamoto et al Prospective 39 PEI Shiina et al Retrospective 122 MCT N/A Lencioni et al RCT 102 PEI N/A RFTA N/A *Small HCC: single lesion 5 cm in diameter or smaller or as many as 3 lesions each 3 cm or smaller. PEI, percutaneous ethanol injection; MCT, microwave coagulation therapy; RFTA, radiofrequency thermal ablation. At 2 years. tumor necrosis as a result of cellular dehydration, protein denaturation, and chemical occlusion of tumor vessels. It is best administered by using ultrasound guidance because real-time control allows for a faster procedure, precise centering of the needle in the target, and continuous monitoring of the injection. Fine noncutting needles, with either a single end hole or multiple side holes, are commonly used for PEI. PEI is usually performed under local anesthesia on an out-patient basis. The treatment schedule typically includes four to eight sessions performed once or twice weekly. The number of treatment sessions, as well as the amount of ethanol to inject, may vary greatly according to the size of the lesion, the distribution of the injected ethanol within the tumor, and the compliance of the patient. Several studies have shown that PEI is an effective treatment for small (3 cm or less), nodular-type HCC. HCC nodules have a soft consistency and are surrounded by a firm cirrhotic liver. Consequently, injected ethanol diffuses within them easily and selectively, leading to complete tumor necrosis in about 70% of small lesions. 7 Although there have not been any prospective randomized trials comparing PEI and surgical resection, several series have shown that the long-term outcome of selected PEI-treated patients was similar to that of patients who had undergone resection, with 5-year survival rates of 32 59% (Table 1) While PEI is a low-risk procedure, severe complications, including cases of tumoral seeding, have been reported. 13 The major limitation of PEI, besides the uncertainty of tumor ablation and the long treatment time, is the high local recurrence rate, that may reach 33% in lesions smaller than 3 cm and 43% in lesions exceeding 3 cm. 14,15 The injected ethanol does not always accomplish complete tumor necrosis because of its inhomogeneous distribution within the lesion especially in the presence of intratumoral septa and the limited effect on extracapsular cancerous spread. Also, PEI is unable to create a safety margin of ablation in the liver parenchyma surrounding the nodule, where satellite nodules are most frequently located. 16 RF Thermal Ablation Basic Principles The goal of RF ablation is to induce thermal injury to the tissue through electromagnetic energy deposition. In RF ablation, the patient is part of a closed-loop circuit, that includes an RF generator, an electrode needle, and a large dispersive electrode (ground pads). An alternating electric field is created within the tissue of the patient. Because of the relatively high electrical resistance of tissue in comparison with the metal electrodes, there is marked agitation of the ions present in the target tissue that surrounds the electrode, since the tissue ions attempt to follow the changes in direction of alternating electric current. The agitation results in frictional heat around the electrode. The discrepancy between the small surface area of the needle electrode and the large area of the ground pads causes the generated heat to be focused and concentrated around the needle electrode. 17 The thermal damage caused by RF heating is dependent on both the tissue temperature achieved and the duration of heating. Heating of tissue at 55 C for 4 6 minutes produces irreversible cellular damage. At temperatures between 60 C and 100 C near immediate coagulation of tissue is induced, with irreversible damage to mitochondrial and cytosolic enzymes of the cells. Over C, tissue vaporizes and carbonizes. For

3 Percutaneous Ablation of Hepatocellular Carcinoma S93 adequate destruction of tumor tissue, the entire target volume must be subjected to cytotoxic temperatures. Thus, an essential objective of ablative therapy is achievement and maintenance of a C temperature throughout the entire target volume for at least 4 6 minutes. However, the relatively slow thermal conduction from the electrode surface through the tissues may increase the duration of application up to 30 minutes. On the other hand, the tissue temperature should not be increased over these values to avoid carbonization around the tip of the electrode due to excessive heating. 17 In the early experiences with RF ablation, a major limitation of the technique was the small volume of necrosis created by conventional monopolar electrodes. 17 These devices were capable of producing cylindrical lesions not greater than 1.6 cm in diameter. Therefore, multiple electrode insertions were necessary to treat all but the smallest lesions. Subsequently, several strategies for increasing the area of thermal necrosis achieved with RF treatment have been tested, including the use of multiprobe arrays, bipolar arrays, and saline injections during RF application. These devices were shown to increase the volume of coagulation necrosis that can be obtained in a single treatment session. However, such techniques were either technically challenging and time-consuming or produced irregularly shaped thermal lesions, thereby substantially limiting their clinical usefulness. Major progress in RF technology was achieved with the introduction of modified electrodes, including cooled-tip electrode needles and expandable electrode needles with multiple retractable lateral-exit prongs on the tip Cooled-tip electrodes consist of dual-lumen needles with uninsulated active tips, in which internal cooling is obtained by continuous perfusion with chilled saline. Needle cooling is aimed at preventing overheating of tissues nearest to the electrode, which may cause charring, thereby limiting the propagation of RF waves. They are available either as a single needle or as a cluster array with three needles spaced 0.5 cm apart. Expandable needles have an active surface that can be substantially expanded by hooks deployed laterally from the tip. The number of hooks and the lenght of the hooks deployment may vary according to the desired volume of necrosis. These techniques enabled a substantial and reproducible enlargement of the volume of thermal necrosis produced with a single needle insertion, and prompted the start of clinical application of RF ablation. Materials and Methods At our institution, we currently use 150- or 200-W RF generators and 14-gauge expandable electrode needles (StarBurst XL, RITA Medical Systems). The needle electrode consists of an insulated outer cannula that houses nine curved electrodes of various lengths, which deploy out from the trocar tip. This design decreases the distance between the tissue and the electrodes, thereby ensuring uniform heating that relies less on heat conduction over a large distance. Five of the electrodes are hollow and contain thermocouples in their tips that are used to measure the temperature of the adjacent tissue. Probetip temperatures, tissue impedance, and wattage are displayed on the RF generator and graphically recorded by dedicated software, installed on a personal computer. Maximum power output of the RF generator, amount of electrode array deployment from the trocar, and duration of the effective time of the ablation (time at target temperature) depend on the desired volume of ablation. This is established at the beginning of the procedure with the goal of destroying the visible tumor mass plus a 1-cm safety margin of ablation all around. To perform a typical ablation, two grounding pads are placed on the patient s thighs. The tip of the needle (with retracted electrodes) is advanced under ultrasound guidance to the proximal edge of the lesion, and the electrodes are deployed to 2 cm. The generator is turned on and runs by an automated program. The temperatures at the tips of the electrodes are controlled and the peak power is maintained until the temperature exceeds the preselected target temperature (typically between 90 and 100 C). After the target temperature is achieved, the curved electrodes are advanced step-bystep to full deployment. When the electrodes are fully deployed, the program maintains the target temperature by regulating the wattage. At the end of the procedure, when the generator turns off, a cool down cycle is automatically performed. After retracting the hooks, the coagulation of the needle track can be performed (track ablation) to maintain the temperature above 75 C with the aim of preventing any tumor cell dissemination. In our center, percutaneous RF is usually performed under conscious sedation. The association of a hypnotic drug with an ultrashort half-life analgesic drug allows a mild sedation that allows the patient to co-operate with the operator and bear the pain induced by treatment. Our standard protocol consists in administering a bolus of ketorolac ( mg/kg) followed by infusion of propofol (1 2 mg/kg/h) and remifentanil (0.1 mg/kg/min). However, drug posology has to be modulated in relation to the individual patient compliance and to the different phases of the procedure. The infusion of the hypnotic drug can be varied between 0.5 and 2 mg/kg/h to achieve a patient sedation that preserves the ability to perform simple actions. The infusion of remifentanil can be varied between 0.05 and 0.15 kg/min to obtain an optimal analgesia. Attention has to be made in order to avoid bolus administration of remifentanil, as this may cause respiratory depression. The procedure is performed under standard car-

4 S94 Lencioni et al diac, pressure, and oxygen monitoring with continuous oxygen administration. A careful post-treatment protocol is to be recommended following RF ablation. The patient is kept under close medical observation and re-scanned with ultrasound 1 2 hours after the procedure. An overnight hospital stay is scheduled. Contrast-enhanced ultrasound performed shortly after the procedure may allow an initial evaluation of tumor response, by showing disappearance of intratumoral signals. 21,22 Spiral CT obtained 1 3 days after the ablation shows a core of hypoattenuation surrounded by an enhancing rim. 23 The peripheral enhancing rim which is due to the inflammatory reaction surrounding the area of necrosis should not be misinterpreted as tumor persistence. Since the enhancing rim tends to disappear over time, spiral CT at 1 month is considered the most reliable method to evaluate the outcome of treatment. 1 If there is imaging evidence of residual tumor, the patient can be considered for repeated RF ablation, provided that requirements for treatment are still met. Follow-up ultrasound and spiral CT studies are usually scheduled at 3- or 6-month intervals. Clinical Results In most clinical experiences with RF thermal ablation, patients were treated in the framework of feasibility studies, aimed at analyzing safety, tolerability, and local therapeutic effect of the treatment. Rossi et al 20 treated 37 patients with liver tumors with an expandable RF electrode needle, in the absence of major complications. Twenty-three of the 37 patients had HCC nodules smaller than 3.5 cm. All the HCC nodules did not show any residual viable tissue on post-treatment CT scans. Complete tumor necrosis was confirmed in two patients who underwent surgical resection after RF treatment. In the series of Shirato et al, of 30 HCC nodules smaller than 3 cm did not show residual tumor on imaging studies performed after RF ablation, and did not show any local recurrence after a follow-up period of 3 15 months (mean, 8.4 months). Livraghi et al. 25 also reported that complete response was seen on post-treatment CT in 47 of 52 HCC lesions smaller than or equal to 3 cm in diameter after treatment with cooled-tip RF ablation. The rate of complete responses was higher than that achieved by the same authors in a group of comparable patients who underwent PEI (90% vs. 80%). In addition, the average number of treatment sessions needed to achieve ablation was substantially lower for RF than for PEI. However, one major complication and four minor complications occurred in patients treated with cooledtip RF ablation, whereas no complications occurred in patients treated with PEI. A similar comparative study was performed by Ikeda et al. 26, who treated a series of 119 consecutive patients with solitary HCC smaller than 3 cm with either RFA (n 23) or PEI (n 96). Complete tumor response on imaging was achieved in 23 patients (100%) treated with RF and in and 90 patients (94%) treated by PEI. RF required an average of 1.5 sessions to achieve complete ablation vs. an average of 4 sessions of PEI. There were no serious adverse effects or complications except for one case of cholangitis after PEI. One of the current recommendations for research proposed by the European Association for the Study of the Liver is a comparison of newer methods of tumor destruction, such as RF, with the well-established and accepted PEI through randomized trials assessing not only initial tumor response, but also long-term survival outcomes. 1 We therefore undertook a prospective randomized study aimed at comparing the efficacy of RF ablation with that of PEI for the first-line treatment of small HCC in cirrhosis. 27 Primary end-point of the study was overall survival. Secondary end-points were local recurrence-free survival and event-free survival (i.e., survival free from local recurrence, new HCC tumors, and extrahepatic metastases). Fifty-two patients with 69 HCC tumors were treated with RF ablation ( RF group ), while 50 patients with 73 HCC tumors received PEI ( PEI group ). No statistically significant differences between RF and PEI groups were observed with respect to baseline characteristics, except for patients age and albumin concentration. Due to the relatively short observation period and the small number of deaths in both treatment groups, we were not able to demonstrate a statistically significant difference between RF ablation and PEI with respect to overall survival. Nevertheless, a trend towards increased survival in the RF thermal ablation group was obvious. The overall survival rates after 1 and 2 years were 96% and 88%, respectively, in the PEI group, and 100% and 98%, respectively, in the RF group (p 0.138, Table 1). However, 1- and 2-year local recurrencefree survival rates were significantly higher in the RF group (98% and 96%, respectively) than in the PEI group (83% and 62%, respectively, p 0.002). One- and 2-year event-free survival rates were also higher in RF-treated patients (86% and 64%, respectively) than in PEI-treated patients (77% and 43%, respectively, p 0.012). RF treatment was confirmed as an independent prognostic factor for local recurrence-free survival by multivariate analysis (adjusted RR 0.20, p 0.015). Despite the fact that the RF generator used in this study has been currently replaced by newer devices, RF ablation was shown to be more effective than PEI in the treatment of small HCC in cirrhosis. However, treatment of large tumors is still problematic. Livraghi et al. 28 treated 114 patients with 126 HCC lesions greater than 3 cm in diameter. Complete necrosis (on imaging) was attained in only 60 lesions (47.6%), nearly complete (90 99%) necrosis in 40 lesions (31.7%), and partial (50 89%) necrosis in the remaining 26 lesions (20.6%). Medium and/or noninfiltrating tumors were treated successfully significantly more often than large and/or infiltrating tumors. Therefore, there is currently a focus on a multimodality strategy in attempts to ensure a more effective treatment of large tumors. Recent studies have proved the influence of perfusionmediated tissue cooling on the area of thermal necrosis achievable with RF treatment. Goldberg et al. 29 applied RF in vivo to normal porcine liver without and with balloon occlusion of

5 Percutaneous Ablation of Hepatocellular Carcinoma S95 the portal vein, celiac artery, or hepatic artery, and to ex vivo calf liver: RF application during vascular occlusion produced larger areas of coagulation necrosis than RF with unaltered blood flow. The same authors demonstrated that intraoperative RF application produced greater coagulation diameter for human hepatic metastases treated during portal inflow occlusion than for tumors treated with normal blood flow. Assuming that the volume of thermal necrosis produced by RF treatment is strongly dependent on blood flow, and considering that in HCC blood flow is mainly sustained by the hepatic artery, we designed a multicenter clinical trial aimed at investigating whether interruption of the tumor arterial blood supply by means of occlusion of either the hepatic artery with a balloon catheter or the feeding arteries with gelatin sponge particles would increase the extent of RF-induced coagulation necrosis. 30 A series of 62 consecutive patients with a single, large HCC ranging from 3.5 to 8.5 cm in diameter (mean, 4.7 cm) accompanying cirrhosis underwent RF ablation after occlusion of the tumor arterial supply. The RF energy was delivered by using an expandable electrode needle at the time of balloon catheter occlusion of the hepatic artery (n 40), at the time of occlusion of the HCC feeding arteries with gelatin sponge particles (n 13), or 2 5 days thereafter (n 9). Two patients underwent liver resection after the thermal ablation; the remaining 60 patients were followed for a mean of 12.1 months (range, 3 26 months). During the follow-up, 49 (82%) of the 60 treated HCC nodules showed stable complete response, while the remaining 11 (18%) nodules showed local progression. Histopathologic analysis of one autopsy and of the two surgical specimens revealed more than 90% necrosis in one specimen and 100% necrosis in two. No fatal or major complications related to the treatment occurred, despite the more aggressive RF treatment protocol. Results of this study provide evidence that areas of coagulative necrosis that are much larger than those previously reported can be created if RF thermal ablation is performed in HCC nodules after occlusion of their arterial supply. The results achieved with this technique were confirmed by two recent studies. Yamasaki et al. 31 compared the coagulation diameters obtained with balloon-occluded RF and standard RF in 31 patients with 42 HCC lesions measuring less than 4 cm in the greatest dimension. There were no significant differences in ablation conditions such as the frequency of a fully expanded electrode, the number of needle insertions, application cycles, or treatment times between the two groups. However, the greatest dimension of the area coagulated by balloonoccluded RFA was significantly larger than that coagulated by standard RFA. Yamakado et al. 32 evaluated the local therapeutic efficacy of RF ablation after transarterial chemoembolization in 64 patients with 108 lesions. Sixty-five lesions were small (3 cm or less), 32 were intermediate in size (3.1 5 cm), and 11 were large ( cm). Complete necrosis was achieved in all lesions, and there were no local recurrences in small and intermediate-sized lesions during a mean follow-up of 12.5 months. In most of the reported series, RF ablation was associated with acceptable morbidity. Nevertheless, one study raised concerns regarding the risk of tumor seeding following RF ablation: in this experience, four (12.5%) of 32 patients treated by cool-tip RF ablation showed biopsy-proven needletrack seeding between 4 and 18 months after treatment. 33 Iatrogenic tumor dissemination was related to subcapsular location or an invasive tumoral pattern, as shown by a poor differentiation degree. 33 More recently, the incidence of complications following RF ablation was assessed by two large analyses. The first report is a multicenter survey in which 2320 patients with 3554 lesions were included. 34 The majority of patients (1610) had HCC with chronic liver disease. Six deaths (mortality rate, 0.3%) were noted, including two caused by multiorgan failure following intestinal perforation; one case each of septic shock following Staphylococcus aureuscaused peritonitis, massive hemorrhage following tumor rupture, liver failure following stenosis of right bile duct; and one case of sudden death of unknown cause 3 days after the procedure. Fifty (2.2%) patients had additional major complications. Tumor seeding, in particolar, occurred in 12 (0.5%) of 2320 patients. The second report is a multicenter study in which 872 patients (548 of whom with HCC and 324 with or hepatic metastases) were included. 35 Overall, 1263 lesions (741 HCCs and 522 metastases) were treated. The analysis of variance (ANOVA test) was used to evaluate relationships of complications with patient-, tumor-, and procedure-related factors. One case of death (mortality rate, 0.1 %) caused by multiorgan failure following peritonitis due to colonic perforation occurred in a cirrhotic patient with a superficially located HCC. Major complications were observed in 27 (3.1 %) of 872 patients, including 7 cases (0.8%) with tumor seeding along the needle track. 35 Results of these studies confirm that RF ablation is a relatively lowrisk procedure for the treatment of focal liver tumors. Nevertheless, the technique is not entirely free from complications, and appropriate experience and optimized treatment protocols are needed. Also, subcapsular HCC lesions should be treated with caution as they appear to be associated with a higher risk of complications. Other Methods of Percutaneous Ablation Other methods of percutaneous ablation have been clinically tested over the past few years. Ohnishi et al. 36 compared percutaneous acetic acid injection and PEI. Sixty patients with one to four HCCs smaller than 3 cm were entered into a randomized controlled trial. Thirty-one and 29 patients, respectively, were treated by percutaneous acetic acid injection using 50% acetic acid or by PEI using absolute ethanol. All original tumors were treated successfully by either therapy. However, 8% of 38 tumors treated with percutaneous acetic acid injection and 37% of 35 tumors treated with PEI developed a local recurrence (p.001) during the follow-up periods of 29 8 months and months, respectively. The 1- and 2-year survival rates were 100% and 92% in percuta-

6 S96 Lencioni et al neous acetic acid injection and 83% and 63% in percutaneous ethanol injection (p.0017). A multivariate analysis of prognostic factors revealed that treatment was an independent predictor of survival. The authors concluded that percutaneous acetic acid injection was superior to PEI in the treatment of small HCC. However, the results of acetic acid injection were not established in large series of patients. Other groups investigated the usefulness of percutaneous microwave coagulation therapy (MCT). Seki et al. 37 performed a retrospective study in which 90 patients with small HCC were included. The overall 5-year survival rate for patients with welldifferentiated HCC treated with MCT (70%) and PEI (78%) were not significantly different. Among the patients with moderately or poorly differentiated HCC, overall survival with MCT was significantly better than with PEI (5-year survival rate, 35%) (p 0.03), and 9 of 22 patients with moderately or poorly differentiated HCC treated with PEI experienced recurrence in the original target subsegment compared to 2 of 25 patients treated with MCT. The authors concluded that MCT may be superior to PEI for the local control of moderately or poorly differentiated small HCC. Shibata et al. 38 compared the effectiveness of MCT with that of RF ablation in 72 patients with 94 HCC nodules who were randomly assigned to PMC and RF ablation groups. The number of treatment sessions per nodule was significantly lower in the RF ablation group than in the MCT group (1.1 vs. 2.4; p.001). Complete therapeutic effect was achieved in 41 (89%) of 46 nodules treated with MCT and in 46 (96%) of 48 nodules treated with RF ablation (p.26). Major complications occurred in four patients treated with MCT and in one patient treated with RF ablation (p.36). During follow-up (range, 6 27 months), residual foci of untreated disease were seen in 8 of 46 nodules treated with MCT and in 4 of 48 nodules treated with RF ablation. They concluded that MCT and RF ablation had equivalent therapeutic effects, but that RF achieves tumor ablation with fewer sessions. Recently, Adam et al. 39 compared the complication and success rates in patients treated with percutaneous cryosurgery (PCS) or percutaneous RF ablation for unresectable hepatic malignancies. Sixty-four patients were treated with either PCS (n 31) or PRF (n 33). Patient treatment was based on the random availability of the probes. The distribution of tumor types was similar in the two groups (p.76). Initial treatment success was comparable in the two treatment groups. However, local recurrences occurred more frequently after PCS than after RF ablation (16 [53%] of 30 vs. 6 [18%] of 34; p.003). Multivariate analysis demonstrated that the use of PCS (p.003) was an independent risk factor for local tumor recurrence. The authors concluded that, while similar initial treatment success and complication rates are observed following either PCS or RF ablation, local recurrences occur more frequently following PCS. Conclusion From the early studies with PEI to the latest reports on RF ablation, percutaneous techniques have been refined and their clinical efficacy better defined. While PEI is a valuable and accepted treatment for small HCC lesions, RF ablation seems to achieve more effective local control of disease with fewer treatment sessions and appears to be superior to PEI as well as to other chemical or thermal methods of tissue destruction. RF ablation could therefore be currently considered as the first-line treatment of choice for patients with small HCC who are not suitable candidates for resection or transplantation. Nevertheless, further studies investigating the long-term outcomes of RF-treated patients are warranted to fully establish the clinical efficacy of this technique. PEI as well as segmental transarterial chemoembolization will continue to have a valuable complementary role in patients with early-stage HCC. Appropriate use of each treatment technique can only be done when the therapeutic strategy is decided by a multidisciplinary team and is tailored to the individual patient and to the features of the disease. References 1. Bruix J, Sherman M, Llovet JM, Beaugrand M, Lencioni R, Burroughs AK, et al. EASL Panel of Experts on HCC. Clinical management of hepatocellular carcinoma. Conclusions of the Barcelona-2000 EASL conference. European Association for the Study of the Liver. 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