Surgical Resection Versus Local Ablation for HCC on ... - Springer Link

J Gastrointest Surg (2012) 16:301–311 DOI 10.1007/s11605-011-1745-x

2011 SSAT PLENARY PRESENTATION

Surgical Resection Versus Local Ablation for HCC on Cirrhosis: Results from a Propensity Case-Matched Study Andrea Ruzzenente & Alfredo Guglielmi & Marco Sandri & Tommaso Campagnaro & Alessandro Valdegamberi & Simone Conci & Fabio Bagante & Gianni Turcato & Mirko D’Onofrio & Calogero Iacono Received: 3 May 2011 / Accepted: 13 October 2011 / Published online: 18 November 2011 # 2011 The Society for Surgery of the Alimentary Tract

Abstract Background Surgery for hepatocellular carcinoma (HCC) had great improvements in the last decades with low morbidity and mortality and good long-term results. Percutaneous local ablative therapies (LAT) such as radiofrequency ablation and ethanol injection (PEI) for HCC gained consent for their efficacy and safety. In retrospective studies, patients submitted to resection (LR) or LAT frequently have important selection bias. Propensity case-matched analysis proved to reduce selection bias of retrospective studies and allow comparison between different therapies. Aim The aim of this study was to evaluate survival comparing LR and LAT in two groups of cirrhotic patients with HCC matched with propensity score methods. Methods Four hundred and seventy-eight cirrhotic patients with HCC treated with LR or LAT with curative intent between January 1995 and December 2009 were included in the study. One hundred and eighty-one patients underwent LR, and 297 patients were treated with LAT. Tumor stage and liver function were evaluated in all patients. To balance the covariates in the two groups, a one-to-one propensity case-matched analysis was used. A multivariable logistic model based on age, gender, etiology of cirrhosis, Child-Pugh class, number of nodules, maximum diameter of nodules, and serum alphafetoprotein level was used to estimate propensity score. One-to-one caliper matching of LR and LAT groups was performed, generating a matched sample of 176 patients with 88 patients in each group. Results Median survival was 65.1 months (95% CI=48.5–81.7) after LR and 37.3 months (95% CI=29.3–45.3) after LAT (p=0.008). For patients in Child-Pugh class A with single HCC and maximum diameter 3 cm, median survival was 82.9 months (95% CI=52.0–113.7) for the LR group and 18.9 months (95% CI=6.3–31.4) for the LAT group (p=0.001). Conclusion Our propensity case-matched study confirmed that survival is similar after LR and LAT for single HCC smaller than 5 cm and for oligofocal HCC (up to three nodules) smaller than 3 cm; instead, for HCC larger than 5 cm or oligofocal HCC (up to three nodules) larger than 3 cm, surgical resection improves significantly long-term survival. A. Ruzzenente : A. Guglielmi : M. Sandri : T. Campagnaro : A. Valdegamberi : S. Conci : F. Bagante : G. Turcato : C. Iacono General Surgery “A,” Department of Surgery, University of Verona, Verona, Italy A. Guglielmi e-mail: [email protected] M. D’Onofrio Department of Radiology, University of Verona Medical School, Verona, Italy

A. Ruzzenente (*) General Surgery “A,” Department of Surgery, University of Verona Medical School, GB Rossi University Hospital, Piazzale LA Scuro 10, 37134 Verona, Italy e-mail: [email protected]

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Keywords Hepatocellular carcinoma . Surgery . Local ablative therapies . Liver cirrhosis

Introduction Recent advances in the diagnosis and treatment of hepatocellular carcinoma (HCC) have improved short- and long-term outcomes after surgical resection.1 Many treatments are now available for HCC, such as transplantation, liver resection (LR), local ablation, and transcatheter arterial chemoembolization (TACE). Proper selection among different treatments is made on the basis of liver function and tumor stage, but clear guidelines are lacking. LR is still the treatment of choice for early-stage HCC with well-preserved liver function; surgery provides good longterm survival but can be applied in only 20–30% of patients with HCC on cirrhosis.2 Local ablative therapies (LAT) such as radiofrequency ablation (RFA) and percutaneous ethanol injection (PEI) were introduced more than 20 years ago and have been widely used in patients with HCC not amenable of LR.3,4 In addition, in selected patients with very early HCC (single, ≤2 cm) and well-preserved liver function, LAT can achieve high long-term survival rates: 5-year survival of 55% in patients with Child-Pugh A class cirrhosis.5 Several cohort studies comparing LR and LAT for patients affected by HCC on cirrhosis have been published in literature: the results of these studies are often conflicting and are affected by the heterogeneity of selection and patient management.6–9 Moreover, two recent randomized trials failed to clarify the role of LAT and LR; the first10 of the two studies showed that survival rates in patients with early HCC (single, ≤5 cm) were similar after LAT and LR, and the second11 demonstrated the superiority of LR also in small HCC (single, ≤3 cm). The aim of this study is to analyze a large cohort of cirrhotic patients with HCC submitted to LR or LAT. After identifying a propensity score-matched cohort of LR/LAT patients, the short- and long-term results of the two therapies were compared in terms of overall survival and disease-free survival.

Material and Methods Inclusion criteria for the study were the presence of single or multiple (up to three nodules) HCC smaller or equal to 6 cm which underwent LR or LAT during the study period from 1995 to 2009. Diagnosis of HCC was based on accordance of two imaging techniques (US, computed tomography (CT), or magnetic resonance imaging (MRI)) showing an arterial enhancement in a focal lesion ≥2 cm or with a combined criteria of an

J Gastrointest Surg (2012) 16:301–311

imaging technique and serum alpha-fetoprotein (AFP) level greater than 400 ng/dL, according to the European Association for Study of the Liver consensus conference criteria. A fine-needle biopsy was performed in patients with uncertain diagnosis.12 Before surgery or LAT, all patients were submitted to complete liver function tests (bilirubin, alkaline phosphatase, AST, ALT, GGT, albumin, prothrombin time), blood count, creatinine level, chest X-rays, liver ultrasound, and abdominal triple-phase CT or/and contrast-enhanced MR. Resection Group During the study period, 181 patients were submitted to LR of HCC. Characteristics of patients submitted to surgery are reported in Table 1. Surgical resection was considered the treatment of choice for patients with Child-Pugh class A cirrhosis and single HCC. Resection was also performed in selected patients with multiple (up to three nodules) HCC or with Child-Pugh class B7 cirrhosis. Type of resection included wedge resections, segmentectomies, bisegmentectomies, and major resections (more than or equal to three segments). LAT Group During the study period, 297 patients submitted to LAT (214 RFA and 83 PEI). Characteristics of patients submitted to LAT are reported in Table 1. LAT was considered the treatment of choice for patients with Child-Pugh class B cirrhosis or with multiple tumors (up to three nodules). A small number of patients with Child-Pugh class A cirrhosis and single tumor was treated with LAT. In these patients, ablative therapy was indicated because tumors were ill located requiring major hepatic resection or for patients' refusal of surgery. All patients included in the study did not have general contraindication to surgery. All the patients underwent LAT with a percutaneous approach under real-time ultrasonography guidance in an operative room setting under conscious sedation or general anesthesia. RFA was the preferred ablative technique, and in all cases, an expandable, electrode-needle type probe, connected to a radio-frequencies generator (RITA Medical System Inc., CA) was utilized. PEI was utilized only for lesions smaller than 1.5 cm with subcapsular location or adjacent to main portal vein or other organs in which RFA was contraindicated. Evaluation of treatment response was performed with CT or MR after 30 days according to mRecist criteria,13 in which complete tumor response is defined as absence of arterial enhancement within or at the periphery of all treated tumors determined by imaging observation (CT or MRI). HCC with incomplete response were re-evaluated for a new LAT session until complete necrosis was obtained. Incom-

J Gastrointest Surg (2012) 16:301–311 Table 1 Baseline variables in LR and LAT subject groups for the unmatched sample

Variable

303

LR n=181 (%)

LAT n=297 (%)

p value

Standardized difference

145 (80.1) 36 (19.9) 66.3 (9.0)a

232 (78.1) 65 (21.8) 68.4 (9.4)a

0.681

4.8

0.042

24.0

107 (59.1) 74 (40.9)

194 (65.3) 103 (34.7)

0.148

1.2

173 (95.6) 8 (4.4)

180 (60.6) 117 (39.4)

0.001

91.1

128 (70.8) 53 (29.2) 5.1 (3.3)a

182 (61.2) 115 (38.7) 3.6 (1.5)a

0.045

18.4

0.001

57.9

142 (78.4) 39 (21.6)

247 (83.0) 50 (17.0)

0.202

10.9

Gender

a

Mean (SD)

b

LR group: HCV positive in 81 of 107 (75.7%) patients; LAT group: HCV positive in 149 of 194 patients (76.8%)

Male Female Age (years) Etiology Viral-associatedb Not viral-associated Child-Pugh class A B Tumor number Single 2–3 Tumor size (cm) AFP (ng/dL) ≤100 >100

plete necrosis after single or multiple LAT was recorded as treatment failure. The treatment of choice in these patients was TACE. Post-treatment Follow-Up Patients were monitored every 3 months by physical examination and serum AFP level, and imaging studies (US, CT, or MR) were performed every 6 months. All patients with intrahepatic recurrence were evaluated for new treatment with LR, LAT (PEI or RFA), and TACE in relation to the severity of liver dysfunction and tumor stage. All patients who, during follow-up after LR or LAT, underwent liver transplantation were excluded from the study group in order to verify the precise role of surgery and LAT without other confounding factors.

Statistical Analysis In the present study, therapy is not randomly assigned but is related to patient characteristics. Hence, the assessment of a causal effect of treatment on survival is hampered by possible confounding. In order to reduce potential bias in effect estimation, we used a propensity score 14 to assess the conditional probability of treatment according to the individual's covariates and to balance treatment choice-related variables such that the analysis simulates random assignment. Propensity score was estimated using a logistic regression model where the outcome is the binary variable LR vs. LAT (0=LR, 1=LAT), and the explanatory variables are age,

sex, etiology of cirrhosis, Child-Pugh class, number of nodules, maximum diameter of nodules, and serum alphafetoprotein level. One-to-one matching without replacement performed by a 0.1 caliper matching on the estimated propensity score generated 88+88 matched LR and LAT units. The degree of covariate imbalance in unmatched (Table 1) and matched (Table 2) samples was measured using the standardized (mean and proportion) difference proposed by Austin et al.15 Overall survival was calculated as the time from the date of treatment until death from any cause or until the end of the observation period. Disease-Free Survival was calculated as the time from the date of treatment until detection of recurrent disease or until the end of the observation period without recurrence. The hazard ratios related to LR vs. LAT therapies were estimated on matched data by Cox proportional hazards models with random effects (frailty).16 The assumption of proportional hazards was verified using the test of Grambsch and Therneau,17 based on Schoenfeld residuals. The proportional hazards assumption was tested globally and for each covariate, with all null hypotheses set at a 5% level of significance. Differences of treatment effects in the four groups according to size and number of HCC were investigated considering in the Cox model the interaction between treatment and group type and by testing (using a likelihoodratio test) whether the coefficient of the interaction term was significantly different from zero. The survival curves of Figs. 1, 2, and 3 were estimated on matched data using the Kaplan–Meier method. Differ-

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Table 2 Baseline variables in LR and LAT subject groups for the matched sample

LR n=88 (%)

LAT n=88 (%)

p value

Standardized difference

72 (81.8) 16 (18.2) 67.4 (8.3)a

69 (78.4) 19 (21.6) 68.4 (9.2)a

0.706

8.5

0.253

11.0

53 (60.2) 35 (39.8)

59 (67.0) 29 (33.0)

0.433

2.4

82 (93.2) 6 (6.8)

81 (92.0) 7 (8.0)

0.783

4.3

58 (65.9) 30 (34.1) 3.7 (1.5)a

55 (62.5) 33 (37.5) 4.0 (1.5)a

0.753

2.8

0.433

15.9

73 (83.0) 15 (17.0)

73 (83.0) 15 (17.0)

1.000

0

Gender

a

Mean (SD)

b

LR group: HCV positive in 43 of 53 (81.1%) patients; LAT group: HCV positive in 49 of 59 patients (83.1%)

Male Female Age (years) Etiology Viral-associatedb Not viral-associated Child-Pugh class A B Number Single 2–3 Size (cm) AFP (ng/dL) ≤100 >100

ences between survival curves were tested in Table 3 using the log–rank test. The hypothesis of independence between two categorical variables was tested by Fisher's exact test. Two-sided p values 100 vs. ≤100 ng/dL) Child-Pugh (B vs. A) Etiology (not viral vs. viral) 2–3 HCCs and size ≤3 cm (n=22) Treatment (LAT vs. surgery) AFP (>100 vs. ≤100 ng/dL) Child-Pugh (B vs. A) Etiology (not viral vs. viral) 2–3 HCCs and size >3 cm (n=41) Treatment (LAT vs. surgery) AFP (>100 vs. ≤100 ng/dL) Child-Pugh (B vs. A) Etiology (not viral vs. viral)

identified similar results between LR and LAT in small HCC (smaller than 3 cm), but results were affected by selection bias between the two groups.6,7 Recently, the 18th Japan nationwide survey in over 10,000 Child-Pugh A patients has reported that survival rate after LR and RFA is comparable in single HCC smaller than 2 cm and in HCC larger than 2 cm but smaller than 5 cm; these results are confirmed at 5 and 10 years follow-up.23 In literature have been published two randomized controlled trials (RCT). The first published in 2006 analyzed the results of 90 patients submitted to RFA and 90 submitted to LR for single HCC smaller than 5 cm in Child-Pugh A patients.10 The authors showed that LAT and LR had similar results in terms of survival and disease-free survival; however it should be underlined that the study had a short follow-up, a cross treatment between LAT group and LR of 20%.10 The other recently published RCT comparing 115 patients within Milan criteria showed the superiority of LR in both survival and disease-free survival; these results were confirmed also in single and small HCCs.11 However, this study had several limitations: cross treatment between LAT and LR was 6%; there was high loss to follow-up, 15% for LR and 6% for RFA; and there was a selection bias with more multinodular HCCs in the RFA group.11 Our study includes a large cohort of patients submitted to surgery or LAT. In unmatched cohorts, the two samples

Disease-free survival 95% CI

p

Hazard ratio

95% CI

p

0.9 3.5 3.8 1.2

0.5–1.8 1.3–10.0 1.4–10.7 0.9–1.5

0.850 0.017 0.011 0.110

1.2 1.2 2.8 1.0

0.7–2.1 0.4–4.1 0.9–8.1 0.5–2.2

0.580 0.770 0.068 0.960

3.8 0.6 0.7 0.8

1.3–11.2 0.2–1.8 0.1–3.1 0.6–1.1

0.016 0.400 0.620 0.150

5.6 0.8 2.0 0.4

2.0–16.0 0.3–2.2 0.5–7.5 0.1–1.2

0.001 0.700 0.320 0.110

2.0 3.8 8.8 0.8

0.5–8.0 0.7–21.4 0.8–97.2 0.5–1.1

0.330 0.130 0.076 0.160

0.9 3.4 4.6 0.2

0.2–3.6 0.6–18.5 0.5–41.8 0.1–0.9

0.890 0.150 0.172 0.038

4.8

1.6–14.4

0.005

3.5

1.5–8.3

4.9 1.6 0.8

1.5–16.5 0.3–7.6 0.7–1.1

0.010 0.580 0.210

3.2 1.7 0.7

1.3–8.0 0.5–5.9 0.3–1.4

0.004 0.015 0.373 0.291

were statistically different in many variables. Propensity score matching was used to generate balanced samples and to decrease the selection bias between the LAT and LR groups. Standardized differences confirmed the good covariate's balance achieved using the matching procedure. Overall and disease-free survival was compared in LATand LR-matched samples, and multivariate analysis was applied to investigate the prognostic value of the observed covariates. The survival analysis confirms that LAT and surgery have comparable results in patients with single HCC smaller than 5 cm and in two to three HCC smaller or equal to 3 cm. These results confirm other findings of the literature.10,19,23 Multivariate analysis showed the prognostic value of AFP and the equivalence of the two treatments. These data emphasize the importance of the biological behavior of the tumor. In single HCCs larger than 5 cm and in two to three HCCs larger than 3 cm, the LR proved its superiority compared to LAT. These data were confirmed also in multivariate analysis. Interestingly, in the multivariate subgroup analysis, we did not identify other significant prognostic factors other than the type of treatment. In these subgroups, the prognostic value of the type of therapy probably exceeds the prognostic value of other important variables such as the AFP levels and the Child-Pugh score. In literature, the recurrence of HCC after curative treatment (surgery or ablation) occurs in more than 70%

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after 5 years. The advent of recurrence is related to a combination of factors related with the tumor stage, the type of treatment, and of liver cirrhosis.2,24 In our study, we found that recurrences were more frequent in the LAT group. In this group, the frequency of early recurrences was significantly higher compared to LR. When we analyzed the disease-free survival in patients with single HCC smaller than 5 cm and two to three HCC smaller than 3 cm, the results of the two groups were comparable. On the contrary, for HCC larger than 5 cm or two to three HCC larger than 3 cm, the disease-free survival was significantly higher in the LAT group; these data were confirmed in multivariate analysis. The local recurrence occurs in 20% of patients after LAT, whereas it occurs rarely after LR.25 In our study, LR and LAT had similar results in terms of local recurrence rate only for HCC smaller or equal to 2 cm. In HCC larger than 2 cm, the local recurrence rate was significantly higher in the LAT group. The frequency of local recurrence in LAT was significantly higher in the HCC located centrally and near major vessels. This observation confirms other reports in literature in which the size and location near major vessels are factors associated with higher local recurrence rate.26,27 A potential limitation of this study is the reduction of sample size after matching that can affect the accuracy of survival-estimated values. However, the one-to-one propensity matching technique allows to obtain highly selected samples that significantly improve the quality of univariate and multivariate analyses.

Conclusions The novelty of our study is the application of propensity case-matched analysis to compare surgery and LAT for the treatment of HCC on cirrhosis. We found that surgery and LAT have comparable survival and disease-free survival for patients with a single HCC smaller than 5 cm or with two to three HCCs smaller than 3 cm. When analyzing local recurrence rate, the two treatments were comparable only for HCCs smaller than 2 cm whereas the local recurrence rate is significantly higher in the LAT group for HCC >2 cm. From the results of our study, LAT can achieve similar results compared to surgery in terms of survival and disease-free survival in patients with single HCC up to 5 cm. When analyzing local recurrence, overall survival and disease-free survival LAT can represent a safe alternative to surgical resection in HCCs smaller than 2 cm. Surgical resection in all patients with HCC larger than 2 cm proved its superiority in terms of local tumor control and long-term results.


References 1. Fan ST, Mau Lo C, Poon RT, et al. Continuous improvement of survival outcomes of resection of hepatocellular carcinoma: a 20year experience. Ann Surg 2011;253:745–58. 2. Poon RT, Fan ST, Lo CM, et al. Improving survival results after resection of hepatocellular carcinoma: a prospective study of 377 patients over 10 years. Ann Surg 2001;234:63–70. 3. Rossi S, Di Stasi M, Buscarini E, et al. Percutaneous RF interstitial thermal ablation in the treatment of hepatic cancer. AJR Am J Roentgenol 1996;167:759–68. 4. Guglielmi A, Ruzzenente A, Battocchia A, Tonon A, Fracastoro G, Cordiano C. Radiofrequency ablation of hepatocellular carcinoma in cirrhotic patients. Hepatogastroenterology 2003;50:480–4. 5. Livraghi T, Meloni F, Di Stasi M, et al. Sustained complete response and complications rates after radiofrequency ablation of very early hepatocellular carcinoma in cirrhosis: Is resection still the treatment of choice? Hepatology 2008;47:82–9. 6. Vivarelli M, Guglielmi A, Ruzzenente A, et al. Surgical resection versus percutaneous radiofrequency ablation in the treatment of hepatocellular carcinoma on cirrhotic liver. Ann Surg 2004;240: 102–7. 7. Guglielmi A, Ruzzenente A, Valdegamberi A, et al. Radiofrequency ablation versus surgical resection for the treatment of hepatocellular carcinoma in cirrhosis. J Gastrointest Surg 2008;12:192–8. 8. Guo WX, Zhai B, Lai EC, et al. Percutaneous radiofrequency ablation versus partial hepatectomy for multicentric small hepatocellular carcinomas: a nonrandomized comparative study. World J Surg 2010;34:2671–6. 9. Yun WK, Choi MS, Choi D, et al. Superior long-term outcomes after surgery in Child-Pugh class A patients with single small hepatocellular carcinoma compared to radiofrequency ablation. Hepatol Int 2010;5:722–729 10. Chen MS, Li JQ, Zheng Y, et al. A prospective randomized trial comparing percutaneous local ablative therapy and partial hepatectomy for small hepatocellular carcinoma. Ann Surg 2006;243:321–8. 11. Huang J, Yan L, Cheng Z, et al. A randomized trial comparing radiofrequency ablation and surgical resection for HCC conforming to the Milan criteria. Ann Surg 2010;252:903–12. 12. Bruix J SM, Llovet JM, et al. Clinical management of hepatocellular carcinoma. Conclusions of the Barcelona-2000. J Hepatol 2001;35:421–30. 13. Lencioni R, Llovet JM. Modified RECIST (mRECIST) assessment for hepatocellular carcinoma. Semin Liver Dis 2010;30:52– 60. 14. Rosenbaum P, Rubin D. The central role of the propensity score in observational studies for causal effects. Biometrika 1983;70:14. 15. Austin PC, Grootendorst P, Anderson GM. A comparison of the ability of different propensity score models to balance measured variables between treated and untreated subjects: a Monte Carlo study. Stat Med 2007;26:734–53. 16. Clayton D. A model for association in bivariate life tables and its application in epidemiological studies of familial tendency in chronic disease incidence. Biometrika 1978;65:10. 17. Grambsch G, Therneau T. Proportional hazards tests and diagnostics based on weighted residuals. Biometrika 1994;81:11. 18. Peng ZW, Zhang YJ, Chen MS, Lin XJ, Liang HH, Shi M. Radiofrequency ablation as first-line treatment for small solitary hepatocellular carcinoma: long-term results. Eur J Surg Oncol 2010;36:1054–60. 19. Abu-Hilal M, Primrose JN, Casaril A, McPhail MJ, Pearce NW, Nicoli N. Surgical resection versus radiofrequency ablation in the


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Discussant Dr. Clifford S. Cho (Madison, WI): This is a terrific paper. On the one hand, it lends further support to the growing body of evidence that, for small HCC tumors, resection and ablation are both pretty effective. On the other hand, the authors use a careful matched analysis to show that, for patients with compensated liver function and tumor burden exceeding Milan criteria, oncological outcomes are notably worse after ablation than after resection. Compared with transplantation, resection and ablation both suffer the same inherent limitation: leaving behind a sizable portion of potentially tumorigenic liver. This point is exemplified by the authors' observation that rates of distant recurrence were identical after resection and ablation. So the real difference is the purely technical ability of these treatments to control the tumor locally. Indeed, two patients in the resection group suffered local recurrences, whereas 22 patients suffered local recurrences after ablation. Interestingly, nine patients were felt to have incomplete ablations, and for purposes of statistical analyses, they were considered to have recurred at 1 month. My questions really

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center on these nine patients and the impact their inclusion may have had on the authors' conclusions. Were these incomplete ablations recognized at the time of ablation? If so, what would happen if you excluded these patients from analysis? It is more difficult to fully ablate a larger tumor, and eight of these nine treatment failures were in patients with tumors >2 cm—raising the possibility that the superiority of resection for larger tumors may have been entirely referable to this cohort of patients. Was there an obvious technical reason for these nine failures? Were most of these PEI treatments? How many ablations were performed per tumor? In light of the evidence that microwave may be a better modality of ablation than radiofrequency, do you think that effective use of microwave ablation will ameliorate the therapeutic differences between resection and ablation?

Closing Discussant Dr. Andrea Ruzzenente: Thank you Dr. Clifford Cho for your comments and questions. Your comments really identified the most important issue in local ablation of HCC. As we know, after surgery or ablation of HCC, the majority of patients will recur due to the presence of underlying liver disease, but the ability of surgery in local tumor control was one of the major aims of our study. The incomplete ablations after LAT were identified after 30 days CT or MRI imaging; moreover, in all cases, we performed a new session of local ablation. When, after a multiple treatment session, viable tumor tissue was still identified at imaging, we defined the patient with treatment failure. We tried to exclude these patients from the local recurrences analysis, but the surgery was still the treatment with a significant lower rate of tumor recurrence. The size of tumor is the one of the major factors related with treatment failure; the other factors related with higher rate of incomplete ablation are, according our experience, the subcapsular location and the closeness to major vessels. In our cohort, PEI was not related with a higher frequency of incomplete ablation; the 10 patients submitted to PEI had a size smaller than 2 cm and they did not experience local recurrence. The application of microwave seems to allow larger ablations; for this reason, the application of this technology might increase the ability of local ablative therapies to achieve similar results to surgery in larger tumors. We should remember that the size of tumor is related with the presence of tumor satellites and vascular invasion; for this reason, surgery is still the preferred therapy in larger tumors.