Radiofrequency Ablation of Hepatocellular Carcinoma: Correlation Between Local Tumor Progression After Ablation and Ablative Margin

Transcription

1 Radiofrequency Ablation of Hepatocellular Carcinoma Hepatobiliary Imaging Original Research Takahide Nakazawa 1 Shigehiro Kokubu Akitaka Shibuya Koji Ono Masaaki Watanabe Hisashi Hidaka Takeshi Tsuchihashi Katsunori Saigenji Nakazawa T, Kokubu S, Shibuya A, et al. Keywords: abdominal imaging, cancer, hepatocellular carcinoma, liver disease, radiofrequency ablation DOI: /AJR Received November 30, 2005; accepted after revision February 14, All authors: Gastroenterology Division of Internal Medicine, Kitasato University East Hospital, Asamizodai, Sagamihara, Kanagawa , Japan. Address correspondence to T. Nakazawa (tnakazaw@kitasato-u.ac.jp). AJR 2007; 188: X/07/ American Roentgen Ray Society Radiofrequency Ablation of Hepatocellular Carcinoma: Correlation Between Local Tumor Progression After Ablation and Ablative Margin OBJECTIVE. To identify the determinants of tumor progression, we examined the ablation zones and patterns of local progression of small single primary hepatocellular carcinomas after radiofrequency ablation. MATERIALS AND METHODS. Eighty-five patients with single primary hepatocellular carcinoma less than 3 cm in diameter underwent complete tumor ablation. Clinical and biochemical features, tumor characteristics, tumor location within 5 mm from intrahepatic vessels, needle biopsy before treatment, and presence of ablative margin of 5 mm or more were statistically analyzed as determinants of local tumor progression. The Kaplan-Meier method and a Cox model were used for the analyses. Patterns of local tumor progression were examined by image analysis. RESULTS. During a median observation period of 30.3 months, 14 (16.5%) of the 85 patients had local tumor progression. The results of the log-rank test showed that the presence of vessels contiguous with the tumor (p = ) and the absence of an ablative margin of at least 5 mm (p = 0.019) significantly correlated with local tumor progression. Cox regression analysis showed that the absence of an ablative margin of at least 5 mm was an independent factor (p = 0.04). The most common pattern of local tumor progression was a single viable outgrowth from the side of the ablated area when the ablative margin was less than 5 mm. Multiple viable outgrowths were observed in one case despite the presence of an ablative margin greater than 5 mm. CONCLUSION. An ablation zone with an ablative margin of 5 mm or greater was the most important factor for local control of hepatocellular carcinoma. epatocellular carcinoma (HCC) is H one of the most common malignant tumors worldwide [1]. HCC frequently recurs after curative treatment, leading to high mortality rates [2, 3]. Surgical resection and orthotopic hepatic transplantation are curative treatments of HCC but are often not feasible. A shortage of donors limits the possibilities for orthotopic hepatic transplantation, and surgical resection is frequently precluded because of poor hepatic reserve due to liver cirrhosis. Radiofrequency ablation is therefore widely used to control locoregional disease. Good outcome has been obtained with respect to survival and local control [4 11]. Radiofrequency ablation with a percutaneously inserted electrode ablates tumors more completely than other locoregional treatments, reducing the rate of local recurrence [10, 11]. To further improve local disease control and outcome, several studies have been conducted to analyze risk factors and patterns of local recurrence after radiofrequency ablation of HCC. The presence of vessels around HCC, a tumor size of 2 cm or greater, and tumor location near the liver surface have been identified as risk factors for local recurrence [6 8]. Vessels around HCC are minimally affected by radiofrequency ablation, increasing the risk of local recurrence [12]. Other factors potentially related to local control of HCC involve the ablation zone [13]. Complete ablation of HCC is required for prevention of local recurrence and a good prognosis [6, 14]. After complete ablation, the ablation zone is completely surrounded by an avascular area with a contrast defect identifiable on dynamic contrast-enhanced CT. Despite complete ablation, however, outgrowths sometimes develop around ablated areas [15], and the presence of residual cancer cells can lead to regrowth of the tumor. Therefore, the term local tumor progression is more accurate than the term local recurrence [16]. Ablation of appropriate margins beyond the tumor is necessary to achieve complete tumor destruction, and the 480 AJR:188, February 2007

2 Radiofrequency Ablation of Hepatocellular Carcinoma term ablative margin is proposed to describe this 0.5- to 1.0-cm-wide region [13, 16]. Ablative margin is one possible determinant of local tumor progression after complete ablation. In this study, we examined various factors, including ablative margin, that may correlate with local progression of primary single HCC after complete radiofrequency ablation. The pattern was assessed by imaging analysis in patients with local tumor progression. Materials and Methods Clinical Features of Patients Between October 1999 and December 2004, radiofrequency ablation was used to treat 383 patients with HCC at Kitasato University East Hospital. Ninety-four patients were included in the study on the basis of the inclusion criteria. Inclusion criteria were adult patient with a single primary HCC smaller than 3 cm in diameter, no eligibility for surgical resection or refusal of surgery, liver function classified as Child-Pugh class A or B, platelet count greater than /µl, and prothrombin activity greater than 40%. Exclusion criteria were previous treatment of HCC, incomplete ablation of HCC, presence of extrahepatic metastasis or vascular invasion, and follow-up period of less than 6 months. Nine patients were excluded. In five of these nine patients, tumor ablation was incomplete because HCC involved the lung, gallbladder, liver surface, or a combination of these areas. In the other four patients, the follow-up period was less than 6 months because of death from rupture of esophageal varices or because the patient had moved and was lost to follow-up. Eighty-five patients underwent technically successful complete ablation with an ablative margin and were included in the study. The diagnosis of HCC was established on the basis of radiologic features compatible with HCC on contrast-enhanced multiphase helical CT scans or dynamic contrast-enhanced MR images (n = 45) and histologic confirmation (n = 36). The other four patients had tumors with a serum α-fetoprotein level > 20 ng/dl or a level of protein induced by vitamin K absence or antagonism II (PIVKA-II) > 40 mau/ml. Sixty-four (75%) of the patients had positive results for anti hepatitis C virus, and 13 (15%) had positive results for hepatitis B surface antigen. Fifty-nine (69%) of the patients had a serum α-fetoprotein level > 20 ng/dl or PIVKA-II level > 40 mau/ml. The median diameter of the HCC nodules was 20 mm (range, mm). Tumor location was described according to Couinaud segmental anatomic classification. Eighty-two patients had liver cirrhosis, and three had chronic hepatitis. Clinical stage was defined according to Child-Pugh classification and Japan Integrated Staging score [17]. Fifty (59%) and 35 (41%) of the patients had disease in Child-Pugh classes A and B, respectively. The Japan Integrated Staging score was 0 in 48 patients, 1 in 36 patients, and 2 in one patient. Our study was performed in accordance with the guidelines of our institutional review board, and written informed consent was obtained from all patients before treatment. Radiofrequency Thermal Ablation Eighty-two patients were treated by percutaneous radiofrequency ablation under real-time sonographic guidance (model 6500, Aloka Medical Systems) with a 3.75-MHz probe. Three patients were treated under CT guidance. Fifty-five (65%) of the patients were treated with multitined expandable electrodes, and 30 (35%) were treated with internally cooled electrodes. Conscious sedation with a combination of pethidine hydrochloride 35 mg (Opystan, Tanabe) and fentanyl citrate 0.1 mg (Fentanest, Sankyo) was administered IV. Radiofrequency ablation was performed with one of three devices. Twenty-seven patients were treated with 25-cm-long, 15-gauge multitined electrodes with a 1-cm-long tip expandable by four to seven hooks to a maximum diameter of 3 cm (model 30 or 70, RITA Medical Systems). A 460- khz radiofrequency generator (model 500PA, RITA Medical Systems) was activated, and the power needed to maintain a temperature of C at the tip was delivered for 8 minutes. After the first ablation, the hooks were retracted, and the electrode was rotated 45. The hooks were redeployed, and the radiofrequency generator was reactivated for an additional 8 minutes. Twenty-eight patients were treated with hooked, 25-cm-long, 15-gauge multitined electrodes expandable by 10 hooks to a maximum dimension of 3 cm (LeVeen needle electrode, RadioTherapeutics), and radiofrequency ablation was applied with a 460-kHz radiofrequency generator (RTC 2000, Boston Scientific Japan). Initial output was set to 40 W, and the output was increased 10 W every 60 seconds until the peak power of 90 W was attained. Ablation was maintained at peak power for at least 15 minutes. Thirty patients were treated with 25-cm-long, 17-gauge internally cooled electrodes with an exposed 2- to 3-cm metallic tip capable of producing 200 W of power. These electrodes were attached to a 480-kHz radiofrequency generator (CC1, Radionics). A peristaltic pump was used to deliver chilled saline solution in a cannula sheath of internally cooled electrodes to maintain electrode temperature below 15 C. Radiofrequency current was emitted for minutes per needle electrode insertion with the generator set to deliver the maximum power in the autocontrol mode. An impedance control mode gradually increased the power until the impedance rose to 10 Ω above baseline level. To avoid a further increase in tissue temperature that would likely result in charring, the power was reduced automatically to 10 W for 15 seconds and returned to maximal power until the impedance increased again. The three types of electrodes were used in the order they were introduced to our hospital. The electrodes were inserted in several sites to treat overlapping zones and to enlarge the ablation zone. The initial treatment was planned with one ablation for tumors less than 2 cm in diameter and two or more ablations for tumors with the overlapping technique for tumors 2 3 cm in diameter. When tumor ablation was complete, thermal ablation was performed along the needle track. All patients were carefully observed for treatment-related complications. Image Analysis for HCC and Posttreatment Assessment The following tumor characteristics were analyzed directly from CT scans (n = 82) or MR images (n = 3): tumor size ( 20 mm or < 20 mm in diameter), location within liver, tumor type (simple round tumor or not, subcapsular or nonsubcapsular), and presence of blood vessels (first to third branches of the portal vein and first and second branches of the hepatic veins) within 5 mm from the border of the HCC. A total of 120 ml of nonionic contrast material (Omnipaque [iohexol], Daiichi Seiyaku) was administered with an automatic power injector at a rate of ml/s. Images were obtained before and 30 and 180 seconds after initiation of injection of IV contrast material, representing the unenhanced, hepatic arterial, and equilibrium phases, respectively. Images were obtained in a craniocaudal direction with 7-mm collimation and 7-mm/s table speed during a single breath-hold helical acquisition of seconds. The axial images were reconstructed at intervals of 5 mm. For each patient the ablation zone was examined on axial images in the craniocaudal direction in the same field of view as on the hard copies obtained before and 3 5 days after treatment. The goal of the treatment was to achieve complete ablation in the tumor ablation zones, which were the hypoattenuating unenhanced areas visualized during the arterial and the portal venous phases that were larger than the tumor itself. Additional sessions were scheduled for ablation of residual tumors when irregular peripheral enhancement was confirmed at the margin of the ablation zone on images obtained 3 5 days after the first treatment. The diagnosis and treatment procedures were repeated until complete ablation was achieved during one hospital stay. The presence of an ablative margin of at least 5 mm around the HCC (minimum measure- AJR:188, February

3 Tumor Ablative margin Ablation zone ment of ablative margin) was examined on the final images used during the hospital stay to determine whether ablation was complete. The ablative margin is diagrammatically shown between the arrows in Figure 1A. All variables were assessed by one person and reviewed retrospectively by a second person working independently. The observers therefore were blinded with respect to patient characteristics and outcome. Discrepancies were resolved by consensus. Subsequent diagnostic scans were obtained 1 month after discharge. The followup protocol included measuring α-fetoprotein and PIVKA-II levels and acquisition of CT scans at 4- month intervals to monitor for signs of recurrence. Local Tumor Progression Local tumor progression was defined as development of new tumor around the ablation zone. It was diagnosed on the basis of tumor enhancement at the margin of the ablation zone [15]. The cases were analyzed over time by image analysis to characterize patterns of local tumor progression. A B C D Statistical Analysis of Determinants for Local Tumor Progression Clinical and biochemical features at the time of radiofrequency ablation, tumor characteristics, radiofrequency ablation electrode type (multitined expandable or internally cooled), tumor location, presence of contiguous vessels, hepatic surface (portion of tumor located within 5 mm of the surface of the liver), and Couinaud segment were analyzed. In addition, whether needle biopsy was performed before ablation and whether there was a completely ablated margin of at least 5 mm were analyzed for local tumor progression. Data were expressed as mean ± SD. The Kaplan-Meier method was used to estimate the interval from radiofrequency ablation treatment to local tumor progression. The variables as determinants of local tumor progression were analyzed with the use of the log-rank test. A Cox proportional hazards regression model was used to analyze independent risk factors. All p values were two-tailed. A p value < 0.05 was considered to indicate statistical E Fig year-old man with hepatocellular carcinoma. A, Diagram shows thickness of ablative margin around tumor within ablation zone. B, Sonogram shows tumor (arrowhead) before ablation. C, Sonogram shows tumor after ablation. D, Transverse contrast-enhanced arterial phase helical CT scan shows tumor (arrowhead) before ablation. E, Transverse contrast-enhanced arterial phase helical CT scan shows area in D after ablation. Lesion has been completely ablated. Ablation zone includes ablative margin of more than 5 mm. significance. Statistical analyses were performed with the statistical package SPSS Base 11.0J (SPSS) for Windows (Microsoft). Results No patient had major complications after radiofrequency ablation. The cumulative survival rate was 99% at 1 year and 87% at 3 years. The median follow-up period was 30.3 months (range, months). Forty-five (53%) of the patients were treated in overlapping zones with several insertions. The mean number of radiofrequency ablation treatment sessions needed for complete ablation of HCC was 1.4 (range, 1 4 sessions) during one hospital stay. The average hospital stay was 12 days. Eight patients died of hepatic failure, and one patient died of esophageal varix rupture during follow-up. Local tumor progression was found in 14 patients. The median period until detection of tumor progression was 14.1 months (range, months). The cumu- 482 AJR:188, February 2007

4 Radiofrequency Ablation of Hepatocellular Carcinoma TABLE 1: Determinants of Local Progression of Hepatocellular Carcinoma: Univariate Analysis (n = 85) Variable Value p a Sex Men 50 Women 35 NS Age 65 y Yes 45 No 40 NS Hepatitis C virus Yes 65 No Child-Pugh grade A Yes 50 No 35 NS α-fetoprotein 20 ng/ml Yes 52 No 33 NS Tumor location in segments VI VIII Yes 58 No Tumor diameter 20 mm Yes 52 No 33 NS Simple round tumor Yes 49 No 36 NS Hypervascular tumor Yes 78 No 7 NS Hepatic surface Yes 37 No Capsule Yes 32 No 53 NS Contiguous vessels Yes 43 No Tumor needle biopsy Yes 36 No 49 NS Internally cooled electrode Yes 30 No 55 NS Only 1 treatment session Yes 52 No 33 NS Ablative margin 5 mm of ablation zone Yes 30 No Note NS = not significant. a Kaplan-Meier method and log-rank test. Boldface indicates p < lative rate of local tumor progression was 6.1% at 1 year and 19.5% at 3 years. Table 1 shows determinants of local tumor progression. Clinical laboratory data, HCC diameter, number of treatment sessions, electrode device used, and results of tumor needle biopsy were not significantly related to tumor progression. Presence of vessels contiguous with HCC and an ablative margin of less than 5 mm were significantly related to local tumor progression. The cumulative rate of local tumor progression at 3 years was significantly higher for HCC with contiguous vessels (32%) than for HCC without contiguous vessels (5%) (p = ) (Fig. 2A). The cumulative rate of local tumor progression at 3 years was significantly lower for HCC with an ablative margin of 5 mm or more (3.5%) than for HCC with an ablative margin of less than 5 mm (28.3%) (p = 0.019) (Fig. 2B). Cox regression analysis showed that the presence of an ablative margin of less than 5 mm was a significant independent risk factor for local tumor progression (p = 0.04; relative risk = 8.475; 95% CI, ). A difference between multitined expandable and internally cooled electrodes in rate of development of an ablative margin of 5 mm or more was not observed (35% vs 36%). Figure 3 classifies the lesions according to the presence or absence of contiguous vessels and whether the ablative margin was at least 5 mm or less than 5 mm. The number of HCCs with contiguous vessels and an ablative margin of at least 5 mm was significantly lower than the number of HCCs without contiguous vessels (chi-square test, p = 0.005). The patterns of local tumor progression are shown in Figures 4 6. Outgrowths emerged from the sides of ablative margins less than 5 mm wide (Fig. 4) and from the caudate or cranial sides of ablated regions. In one patient, a recurrence developed on the opposite side of a vessel adjacent to the ablation zone (Fig. 5). Another patient had multiple viable recurrent lesions around the ablation zone contiguous with its border (Fig. 6). Discussion Radiofrequency ablation is often performed instead of surgery in percutaneous management of early HCC and metastatic hepatic tumors [1]. It is useful for the management of unresectable HCC in patients with insufficient hepatic reserve and is less invasive than surgical resection. HCC is associated with a high incidence of intrahepatic recurrence after treatment [2, 3]. Stud- AJR:188, February

5 Rate of Tumor Progression (%) Contiguous vessels (n = 43) Follow-Up Period (mo) No contiguous vessels (n = 42) A Follow-Up Period (mo) Fig. 2 Curves of local tumor progression, calculated by Kaplan-Meier method, according to presence or absence of contiguous vessels and presence or absence of ablative margin 5 mm. A, Graph shows log-rank test result that over time presence of contiguous vessels was associated with significantly higher rate of local tumor progression (p = ). B, Graph shows log-rank test result that over time presence of ablative margin of 5 mm within ablation zone was significantly related to freedom from local recurrence (p = 0.019). Contiguous vessels { Yes: n = HCCs No: n = 42 Ablation zone (ablative margin 5 mm) Yes: n = 9 ) 0 No: n = 34 p = Yes: n = 21 1 No: n = 21 ies [5 8, 10, 11, 18] have shown that after radiofrequency ablation of HCC, the rate of local tumor progression can range from as low as 2% to as high as 53%. Previous studies have shown that tumors exceeding 2 cm in diameter, subcapsular tumors, tumors situated at the liver surface, and incompletely ablated tumors are associated with local tumor progression after radiofrequency ablation [7, 8, 18]. Whether the proximity of a tumor to intrahepatic vessels is a risk factor for local tumor progression after radiofrequency ablation remains controversial [7, 8, 12, 19]. To achieve better local control of HCC managed with radiofrequency ablation, analysis of ablation zones with ablative margins is needed. Therefore, we examined small HCCs that had easily comparable ablative margins within their ablation zones. { { Local tumor progression 2 Rate of Tumor Progression (%) Ablative margin < 5mm (n = 55) Ablative margin 5mm (n = 30) Fig. 3 Chart shows association between local tumor progression and presence of contiguous vessels and ablative margin of 5 mm within ablation zone in 85 patients with hepatocellular carcinoma (HCC). Number of cases of local tumor progression was high for HCCs with contiguous vessels that did not have ablative margin of 5 mm within ablation zone. Proportion of cases with ablative margin of 5 mm was significantly lower in HCCs with contiguous vessels than in those without contiguous vessels (p = 0.005, chi-square test). Ablative margin was not associated with local tumor progression in HCCs without contiguous vessels. Unlike the findings of previous studies [6 8], our results showed that tumor size, capsular HCCs, and location of tumor at the liver surface were not related to local tumor progression. Differences in determinants of local tumor progression may be related to the smaller size of HCCs in our study, the performance of more than two ablations with the overlapping technique for tumors 2 3 cm in diameter, and the presence of complete ablation zones with ablative margins of at least 5 mm from the tumor border. Local tumor progression occurred more than 2 years (range, months) after radiofrequency ablation in four of 14 patients, and the ablative margins in those patients were less than 5 mm. Previous studies have shown that local tumor progression generally develops within 2 years after local ablation [15, 20, 21]. Thus, later local tumor progression can occur after complete ablation without a sufficient ablative margin. Analysis by the log-rank test showed that an ablation zone including an ablative margin less than 5 mm from the tumor border and the presence of blood vessels contiguous with tumors were significantly related to local tumor progression. Multivariate analysis showed that presence of an ablative margin of at least 5 mm was a significant independent factor for local tumor progression. An adequate ablative margin is required because most recurrent lesions emerge from ablation zones within 5 mm from the tumor border, the area most likely to contain viable tumor cells. We found that outgrowth emerged from the side of an incompletely ablated margin, including the caudal and cranial ends of the ablated areas, B 484 AJR:188, February 2007

6 Radiofrequency Ablation of Hepatocellular Carcinoma possibly where the ablative margin was underestimated on single-section helical CT scans obtained after radiofrequency ablation. Local tumor progression also occurs beyond vessels adjacent to an ablation zone in cases of HCC with contiguous vessels (Fig. 5). To inhibit local tumor progression, both stricter evaluation of ablation zones with imaging techniques such as MDCT and the use of radiofrequency techniques to enlarge ablation zones are necessary. Because techniques such as overlapping insertions of electrodes sometimes produce small ablation zones relative to the number A C Fig year-old man with single outgrowth of hepatocellular carcinoma detected 41 months after ablation with expandable multitined electrode. A, Diagram shows ablation zone (shading) and local tumor progression (hatching). B, Transverse contrast-enhanced arterial phase helical CT scan shows tumor (arrowhead) before ablation. C, Transverse contrast-enhanced arterial phase helical CT scan 1 month after ablation. D, Transverse contrast-enhanced arterial phase helical CT scan shows single viable lesion (arrow) that developed 41 months after ablation. of ablations [13], other tumor ablation strategies, such as saline or ethanol injections before radiofrequency ablation and the use of devices such as cooled-tip triple-cluster needles, are effective for developing larger areas of ablation with adequate ablative margins [22 25]. Okusaka et al. [26] reported that small single HCCs (3 cm or less in diameter) with no satellite lesions on preoperative images had microscopic satellite lesions cm from the main tumor. These findings suggest the need for an ablative margin of cm around tumors treated with ablation. Because excessively B D large ablation zones adjacent to blood vessels can cause intravascular thrombosis [27], radiofrequency ablation procedures must be carefully monitored. Our findings suggest that it is difficult to develop an ablative margin of at least 5 mm in the management of HCC with contiguous vessels (Fig. 3). Blood flow reduces the thermal effects of radiofrequency ablation, a phenomenon that increases the likelihood of the presence of residual viable tumor cells [24, 28, 29]. To avoid the heat-sink effects of large vessels, radiofrequency ablation with balloon occlusion of the hepatic vessels, a technique that achieves more extensive ablation than standard radiofrequency ablation, can be used to manage HCC with contiguous vessels [28, 30]. Thus, an ablative margin of 5 mm or more should be required in the management of HCC, especially of lesions with contiguous blood vessels. In cases of HCC without contiguous vessels, local tumor progression was not different in the ablation zones, as shown in Figure 3. The absence of contiguous blood vessels in HCC was significantly associated with location of the tumor near the surface of the liver (n = 24) compared with the presence of contiguous vessels (n = 13) (chisquare test, p = 0.012). The findings suggest that because there is less influence of blood flow around the tumor, the absence of contiguous vessels in HCC allows ablation of necrotic tissue that is closer than can be achieved when contiguous vessels are present. In addition, radiofrequency ablation of tumors at the hepatic surface can leave an area of scar contraction on the liver. These factors might have contributed to the results related to width of ablative margin and local tumor progression in the cases of HCC without contiguous vessels. The present study had several limitations. It was performed as a retrospective singlecenter study, and three models of devices were used for radiofrequency ablation under sonographic guidance, possibly leading to bias. To reduce the effects of the other factors, we focused on patients who had primary single small HCC that was completely ablated. These results must be confirmed in larger prospective studies. In conclusion, the presence of blood vessels contiguous to HCC is related to local tumor progression after radiofrequency ablation. A margin of at least 5 mm around HCC should be completely ablated along with the tumor. This factor is most important for local AJR:188, February

7 A B C D A E B Fig year-old man with recurrent hepatocellular carcinoma that emerged on other side of vessel. Ablation was done with expandable electrode. A, Diagram shows ablation zone (shading) and local tumor progression (hatching). B, Transverse contrast-enhanced arterial phase helical CT scan shows lesion (arrowhead) with contiguous vessels before ablation. C, Transverse contrast-enhanced arterial phase helical CT scan 1 month after ablation shows ablation zone. D, Dynamic phase of transverse contrast-enhanced arterial phase helical CT scan 35 months after ablation shows local tumor progression in ablation zone (arrow). E, Equilibrium phase image corresponding to D shows local tumor progression in ablation zone (arrow). Fig year-old man with multiple viable recurrent lesions around ablation zone after treatment of hepatocellular carcinoma with internally cooled electrode. A, Diagram shows ablation zone (shading) and local tumor progression (hatching). B, Transverse contrast-enhanced arterial phase helical CT scan shows lesion (arrowhead) before ablation. (Fig. 6 continues on next page) 486 AJR:188, February 2007

8 Radiofrequency Ablation of Hepatocellular Carcinoma C D E Fig. 6 (continued) 63-year-old man with multiple viable recurrent lesions around ablation zone after treatment of hepatocellular carcinoma with internally cooled electrode. C, Transverse contrast-enhanced arterial phase helical CT scan 1 month after ablation shows ablation zone. D and E, Dynamic phase of transverse contrast-enhanced arterial phase helical CT scan 9 months after ablation shows multiple recurrent lesions (arrows). Ablation zone has ablative margin of more than 5 mm. Therefore, multiple viable lesions probably involved intrahepatic metastasis or iatrogenic spread. control. Because single or multiple lesions can develop around ablation zones despite the presence of an ablative margin of more than 5 mm, patients should be closely observed, and follow-up examinations should be done at regular intervals. Further studies of the mechanism of local tumor progression after radiofrequency ablation are essential for defining the factors involved. Acknowledgments We thank Naomi Kakutani for assistance preparing the figures. We also thank Robert E. Brandt for help editing the manuscript. References 1. Okuda K. Hepatocellular carcinoma. J Hepatol 2000; 32: Ikeda K, Saitoh S, Tsubota A, et al. Risk factors for tumor recurrence and prognosis after curative resection of hepatocellular carcinoma. Cancer 1993; 71: Poon RT, Fan ST, Lo CM, Liu CL, Wong J. Intrahepatic recurrence after curative resection of hepatocellular carcinoma: long-term results of treatment and prognostic factors. Ann Surg 1999; 229: Livraghi T, Goldberg SN, Lazzaroni S, Meloni F, Solbiati L, Gazelle GS. Small hepatocellular carcinoma: treatment with radio-frequency ablation versus ethanol injection. Radiology 1999; 210: Curley SA, Izzo F, Ellis LM, Vauthey JN, Vallone P. Radiofrequency ablation of hepatocellular cancer in 110 patients with cirrhosis. Ann Surg 2000; 232: Horiike N, Iuchi H, Ninomiya T, et al. Influencing factors for recurrence of hepatocellular carcinoma treated with radiofrequency ablation. Oncol Rep 2002; 9: Hori T, Nagata K, Hasuike S, et al. Risk factors for the local recurrence of hepatocellular carcinoma after a single session of percutaneous radiofrequency ablation. J Gastroenterol 2003; 38: Komorizono Y, Oketani M, Sako K, et al. Risk factors for local recurrence of small hepatocellular carcinoma tumors after a single session, single application of percutaneous radiofrequency ablation. Cancer 2003; 97: Livraghi T, Solbiati L, Meloni MF, Gazelle GS, Halpern EF, Goldberg SN. Treatment of focal liver tumors with percutaneous radio-frequency ablation: complications encountered in a multicenter study. Radiology 2003; 226: Lencioni RA, Allgaier HP, Cioni D, et al. Small hepatocellular carcinoma in cirrhosis: randomized comparison of radio-frequency thermal ablation versus percutaneous ethanol injection. Radiology 2003; 228: Shiina S, Teratani T, Obi S, et al. A randomized controlled trial of radiofrequency ablation with ethanol injection for small hepatocellular carcinoma. Gastroenterology 2005; 129: Patterson EJ, Scudamore CH, Owen DA, Nagy AG, Buczkowski AK. Radiofrequency ablation of porcine liver in vivo: effects of blood flow and treatment time on lesion size. Ann Surg 1998; 227: Dodd GD 3rd, Frank MS, Aribandi M, Chopra S, Chintapalli KN. Radiofrequency thermal ablation: computer analysis of the size of the thermal injury created by overlapping ablations. AJR 2001; 177: Sala M, Llovet JM, Vilana R, et al. Initial response to percutaneous ablation predicts survival in patients with hepatocellular carcinoma. Hepatology 2004; 40: Catalano O, Lobianco R, Esposito M, Siani A. Hepatocellular carcinoma recurrence after percutaneous ablation therapy: helical CT patterns. Abdom Imaging 2001; 26: Goldberg SN, Charboneau JW, Dodd GD 3rd, et al. Image-guided tumor ablation: proposal for standardization of terms and reporting criteria. Radiology 2003; 228: Kudo M, Chung H, Haji S, et al. Validation of a new prognostic staging system for hepatocellular carci- AJR:188, February

9 noma: the JIS score compared with the CLIP score. Hepatology 2004; 40: Harrison LE, Koneru B, Baramipour P, et al. Locoregional recurrences are frequent after radiofrequency ablation for hepatocellular carcinoma. J Am Coll Surg 2003; 197: Goldberg SN, Hahn PF, Tanabe KK, et al. Percutaneous radiofrequency tissue ablation: does perfusion-mediated tissue cooling limit coagulation necrosis? J Vasc Interv Radiol 1998; 9: Rossi S, Di Stasi M, Buscarini E, et al. Percutaneous RF interstitial thermal ablation in the treatment of hepatic cancer. AJR 1996; 167: Ishii H, Okada S, Nose H, et al. Local recurrence of hepatocellular carcinoma after percutaneous ethanol injection. Cancer 1996; 77: Goldberg SN, Solbiati L, Hahn PF, et al. Large-volume tissue ablation with radio frequency by using a clustered, internally cooled electrode technique: laboratory and clinical experience in liver metastases. Radiology 1998; 209: Livraghi T, Goldberg SN, Lazzaroni S, et al. Hepatocellular carcinoma: radio-frequency ablation of medium and large lesions. Radiology 2000; 214: de Baere T, Denys A, Wood BJ, et al. Radiofrequency liver ablation: experimental comparative study of water-cooled versus expandable systems. AJR 2001; 176: Kurokohchi K, Watanabe S, Masaki T, et al. Combination therapy of percutaneous ethanol injection and radiofrequency ablation against hepatocellular carcinomas difficult to treat. Int J Oncol 2002; 21: Okusaka T, Okada S, Ueno H, et al. Satellite lesions in patients with small hepatocellular carcinoma with reference to clinicopathologic features. Cancer 2002; 95: Ng KK, Lam CM, Poon RT, et al. Delayed portal vein thrombosis after experimental radiofrequency ablation near the main portal vein. Br J Surg 2004; 91: Rossi S, Garbagnati F, Lencioni R, et al. Percutaneous radio-frequency thermal ablation of nonresectable hepatocellular carcinoma after occlusion of tumor blood supply. Radiology 2000; 217: McGhana JP, Dodd GD 3rd. Radiofrequency ablation of the liver: current status. AJR 2001; 176: Yamasaki T, Kurokawa F, Shirahashi H, Kusano N, Hironaka K, Okita K. Percutaneous radiofrequency ablation therapy for patients with hepatocellular carcinoma during occlusion of hepatic blood flow: comparison with standard percutaneous radiofrequency ablation therapy. Cancer 2002; 95: AJR:188, February 2007