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Vascular and Interventional Radiology |
1 From the Department of Radiology and Center for Imaging Science (D.C., H.K.L., M.J.K., S.H.L., S.H.K., W.J.L., J.H.L.) and the Department of Surgery (J.W.J., Y.I.K.), Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-Dong, Kangnam-Ku, Seoul 135–710, Korea. Received September 17, 2002; revision requested November 26; final revision received April 27, 2003; accepted June 16. Address correspondence to H.K.L. (e-mail: hklim@smc.samsung.co.kr).
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ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONMATERIALS AND METHODS RESULTSDISCUSSIONREFERENCES |
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MATERIALS AND METHODS: Forty-five patients with 53 recurrent HCC tumors in the liver underwent percutaneous RF ablation with ultrasonographic guidance. All patients had a history of hepatic resection for HCC. The mean diameter of recurrent tumors was 2.1 cm (range, 0.8–4.0 cm). All patients were followed up for at least 10 months after ablation (range, 10–40 months; mean, 23 months). Therapeutic efficacy and complications were evaluated with multiphase helical computed tomography (CT) at regular follow-up visits. Overall and disease-free survival rates were calculated.
RESULTS: At follow-up CT after initial RF ablation, 11 (21%) of 53 ablated HCC tumor sites showed residual tumor or local tumor progression. After additional RF ablation, complete ablation of 46 (87%) of 53 tumors was attained. Also at initial follow-up CT, before either additional RF ablation or other treatment was performed, 21 (47%) of 45 patients were found to have 41 new HCC tumors at other liver sites. Of these, nine tumors in eight patients were treatable with a second application of RF ablation. Overall survival rates at 1, 2, and 3 years were 82%, 72%, and 54%, respectively. No deaths or complications requiring further treatment occurred as a result of RF ablation.
CONCLUSION: Percutaneous RF ablation is an effective and safe method for treating recurrent HCC in the liver after hepatectomy, with a good overall patient survival rate.
© RSNA, 2003
Index terms: Liver, interventional procedures • Liver, surgery, 761.1267, 761.45 • Liver neoplasms, therapy, 761.323 • Radiofrequency (RF) ablation, 761.1269
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODS RESULTSDISCUSSIONREFERENCES |
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Radiofrequency (RF) ablation, an image-guided therapy for local control of tumors, has received increasing attention and is considered a safe and effective treatment for small HCC tumors and other malignant hepatic tumors (15–17). Because most recurrent HCCtumors found at follow-up imaging are small, percutaneous RF ablation is usually feasible. A case report and two reports of research studies in a small number of patients with HCC have indicated the potential usefulness of RF ablation for treating intrahepatic recurrent HCC after surgical resection (18–20). The purpose of our study was to evaluate the therapeutic efficacy and safety of percutaneous RF ablation for recurrent HCC after hepatectomy.
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MATERIALS AND METHODS |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODS RESULTSDISCUSSIONREFERENCES |
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All patients met the following criteria for treatment with percutaneous RF ablation: presence in the liver of a single HCC tumor with a maximum diameter no greater than 4 cm, or presence of multiple (two or three) HCC tumors, each with a maximum diameter no greater than 3 cm; accessibility of tumors via a percutaneous approach; absence of portal venous thrombosis and extrahepatic metastasis; presence of liver cirrhosis of Child-Pugh class A or B; prothrombin time ratio greater than 50%; and platelet count greater than 70,000/µL (70 cells x 109/L). This study was approved by the institutional review board, and written informed consent was obtained from all patients.
The hepatectomy procedures performed in the study patients before RF ablation consisted of extended right lobectomy in two patients, right lobectomy in 14, left lobectomy in five, left lateral segmentectomy in six, other bisegmentectomy in four, unisegmentectomy in 10, and subsegmentectomy in four. No tumor cells were found at histologic analysis of tissue from the margins of resected tumors in any of the patients. The mean interval between initial hepatectomy and RF ablation was 18 months (range, 2–47 months). The diagnosis of recurrent HCC was confirmed with US-guided percutaneous needle biopsy in 20 tumors in 20 patients. The remaining 33 tumors in 25 patients were considered recurrent HCC because of characteristic imaging findings (28 tumors, three-phase helical computed tomography [CT] and conventional angiography) and/or the presence of elevated levels of tumor marker in the blood serum (19 tumors, 
-fetoprotein level > 200 ng/mL [> 200 µg/L]). Of 45 patients, 31 were not considered for repeat hepatectomy and were referred for percutaneous RF ablation because of insufficient hepatic reserve (n = 28) or multiple HCC tumors in different lobes (n = 3). The remaining 14 patients refused repeat hepatectomy and requested percutaneous RF ablation. Thirty-eight patients in the study had liver cirrhosis as a result of hepatitis B (n = 28), hepatitis C (n = 7), or alcoholism (n = 3). The remaining seven patients had hepatitis B without cirrhosis. At the time of RF ablation, the numbers of patients with liver cirrhosis of Child-Pugh class A or B were 29 and nine, respectively.
RF Ablation Procedure
We used four commercially available RF devices manufactured by three different companies (21). During the first 12 months of the study, we used only a 50-W monopolar RF generator (500 series; Radiofrequency Interstitial Thermal Ablation Medical Systems, Mountain View, Calif) and an active expandable RF needle electrode with either four or seven retractable lateral prongs. During the second 12-month period, we used a 150-W RF generator of more recent design (1500 series; Radiofrequency Interstitial Thermal Ablation Medical Systems), which was equipped with a larger RF needle electrode with a diameter of 5 cm. In addition, we used another system (RF 2000; RadioTherapeutics, Mountain View, Calif) that included a 100-W generator, a 15-gauge monopolar electrode array with ten hooklike arms and needle electrodes of 2, 3, and 3.5 cm in diameter (LeVeen; RadioTherapeutics), the largest of which is capable of inducing thermal lesions with a diameter of 4 cm. From July 2000, we also used a different device (Cool-tip; Radionics, Burlington, Mass) equipped with a 200-W generator and two optional electrode configurations—a single 17-gauge straight needle electrode and a cluster of three needle electrodes mounted in a triangular configuration on a common handle. The tips of these needle electrodes are internally cooled with chilled saline solution to increase the size of the lesion created during ablation (22). With the use of this device, thermal lesions with a diameter of 5 cm can be induced. Thus, during the course of the study, RF ablations were performed with the 500 series RF generator in 22 tumors, the 1500 series generator in four, the 2000 series generator in eight, and the Cool-tip system in 19, respectively. We selected the type of RF device to be used in each procedure on the basis of the availability of the device and the size and location of the tumor.
All RF ablations were performed percutaneously with real-time US guidance by one of three experienced radiologists (H.K.L., W.J.L., S.H.K.) with 10, 7, and 5 years of experience, respectively, in performing US-guided interventional procedures such as PEIT. The details of patient preparation and ablation techniques have been reported previously (21,23). RF ablation was performed with intravenous conscious sedation and a one-night hospital stay. The procedure involved ablation not only of the entire tumor but also of a 0.5–1.0-cm margin of apparently normal hepatic tissue surrounding the tumor. For tumors larger than 3 cm in diameter, we often performed multiple overlapping ablations.
CT Examinations
Follow-up examinations of all patients were performed with a helical CT scanner (HiSpeed; GE Medical Systems, Milwaukee, Wis) 1 month after RF ablation. A total of 120 mL of nonionic contrast material containing 300 mg of iodine per milliliter (Ultravist 300; Schering, Berlin, Germany) was administered intravenously at a rate of 3 mL/sec with an automatic power injector. Scanning was performed before the initiation of intravenous contrast material injection and at 30, 60, and 180 seconds after initiation of the injection, to obtain nonenhanced, hepatic arterial, portal venous, and equilibrium phase images, respectively. Scanning was performed in the craniocaudal direction and during a single patient breath-hold, with a collimation of 7 mm, table speed of 7 mm/sec, and total scanning time of 25–30 seconds, depending on liver size. Three experienced radiologists (D.C., M.J.K., J.H.L.) interpreted the CT images together by consensus. The tumors were considered successfully ablated when no enhancement was seen in the region of the ablated lesion on images acquired during the hepatic arterial and portal venous phases. When images of the ablation area showed nodular peripheral enhancement during either the hepatic arterial phase or the portal venous phase, we considered part of the tumor unablated (23). The residual part of the tumor was usually treated with additional RF ablation. If the geometry of the residual tumor was such that additional RF ablation was unfeasible, TACE was performed. If the 1-month follow-up CT images showed successful ablation and no new lesion, contrast-enhanced three-phase helical CT was repeated at 3-month intervals. We considered images that showed residual unablated tumor or local tumor progression at the margins of the ablated tumor to represent unsuccessful RF ablation. When no peripheral enhancement was depicted in the ablation area on CT images obtained at 10-month or subsequent follow-up, we considered complete ablation of the tumor to have been achieved.
Follow-up and Statistical Analyses
Unless the patient died during the follow-up period, all patients were followed up for at least 10 months after RF ablation and underwent at least four follow-up CT examinations. By telephone or mail or both, one of the authors (S.H.L.) interviewed all patients who had failed to appear for their follow-up appointments during the previous month. If the patient had died, the relatives of the patient were contacted and the time of death was verified. We calculated the overall survival and disease-free survival rates by using the Kaplan-Meier method. Survival times were calculated from the time of the first RF ablation performed for HCC. If the patient died of causes other than liver disease or hepatopathy-related complications, the case was censored. Calculations were performed by using statistical software (SPSS version 10.0 for Windows; SPSS, Chicago, Ill).
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RESULTS |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODS RESULTSDISCUSSIONREFERENCES |
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In our study, there were no occurrences of procedure-related mortality or major complications that required treatment. Three patients were found to have HCC metastasis to the lung. Twelve (27%) of the 45 patients died of liver disease or hepatopathy-related complications within a mean of 12 months (range, 2–36 months) after RF ablation. Of the 33 patients who survived longer than 36 months, six developed new HCC tumors in the liver, two developed local tumor progression, two developed both new HCC tumors and extrahepatic metastasis, one developed both local tumor progression and extrahepatic metastasis, and 22 patients (49%) were disease free. Among these 33 patients, the mean duration of follow-up between initial RF ablation and the last follow-up visit was 23 months (range, 10–40 months). Overall survival and disease-free survival curves after RF ablation for recurrent liver tumors are shown in Figure 3; overall survival rates at 1, 2, and 3 years were 82%, 72%, and 54%, respectively. Disease-free survival rates at 1, 2, and 3 years were 57%, 43%, and 34%, respectively.
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DISCUSSION |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODS RESULTSDISCUSSIONREFERENCES |
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According to investigators in one previous study of repeat hepatectomy in patients with recurrent HCC (mainly tumors resulting from metachronous multicentric hepatocarcinogenesis), the 3-year survival rate after repeat hepatectomy was 83% (4). However, most investigators have reported more moderate 3-year survival rates of 37%–71% after repeat hepatectomy (2,3,5,6,26,27).
Until relatively recently, repeat hepatectomy was the preferred treatment because it could provide survival rates comparable to those of initial hepatectomy (6,27,28). Repeat hepatectomy not only can ensure complete resection of intrahepatic recurrent tumors but also provides an opportunity to explore the abdominal cavity for extrahepatic lesions. However, this surgical procedure is highly invasive and involves risks of postoperative morbidity and mortality. The mortality rate after repeat hepatectomy is greater than 2% in specialized institutions, and the postoperative morbidity rate is greater than 10% (6,27). Even with recent improvements in surgical techniques, repeat hepatectomy is less feasible and more difficult to perform than initial hepatectomy. In many patients with intrahepatic recurrent HCC after hepatectomy, the new tumors have been found in the lobe opposite that in which the primary HCC tumor was located and in which initial hepatectomy was performed (29). In addition, the liver tissue that remains after initial hepatectomy often undergoes cirrhotic change due to the loss of liver parenchyma. For these reasons, unfortunately, repeat hepatectomy cannot be performed in most patients with a recurrence of HCC after initial hepatectomy (2,6,9–11).
TACE and PEIT have been the treatments most often used for intrahepatic recurrent HCC after hepatectomy. Many studies of these techniques have been reported (2–6,12–14,26,27). TACE is applicable to almost all patients with intrahepatic tumor recurrence and plays an important role in the treatment strategy for recurrent HCC. Particularly in patients with multifocal recurrence, TACE may be the only feasible treatment. Good short-term results sometimes can be achieved with TACE, although the therapy is not generally considered curative; the long-term survival rate after TACE is lower than that after repeat hepatectomy. The 3- and 5-year survival rates of patients treated with TACE for recurrent HCC after hepatectomy have been reported to be 24%–38% and 0%–21%, respectively (3,12,13). Similar 3- and 5-year survival rates have been reported for PEIT: 22%–76% and 0%, respectively (3,14).
In recent decades, PEIT as a treatment for hepatic tumors increasingly has been supplanted by image-guided tumor ablation applied either percutaneously or intraoperatively (15–17,30). Preliminary results from a number of studies have shown that RF ablation may be a superior option, compared with other tumor ablation techniques (31–33). Although RF ablation has been used to treat recurrent HCC, as well as primary HCC tumors, a survival rate for RF ablation of intrahepatic recurrent HCC tumors after hepatectomy has not, to our knowledge, been reported previously.
However, several studies involving the use of RF ablation to treat intrahepatic recurrent HCC after hepatectomy have been reported. The first was a case study of a patient who was successfully treated with RF ablation (18). In another study, reported by Nicoli et al (19), only one of five patients with intrahepatic HCC recurrence after surgical resection underwent RF ablation; the other four patients underwent TACE. Elias et al (20) reported a study of 47 patients who underwent RF ablation for recurrent tumors after surgical resection of hepatic tumors of various histologic types; but 29 of the patients had recurrent hepatic metastases from colorectal cancer, and only five patients had recurrent HCC tumors. To the best of our knowledge, our study was the first assessment of survival results in patients treated with RF ablation for intrahepatic recurrent HCC after hepatectomy.
Percutaneous RF ablation has advantages over repeat hepatectomy: It is less invasive, and the morbidity and mortality rates associated with it are low. In our study, we found no procedure-related mortality. Percutaneous RF ablation may be the superior option, both for its convenience and for its safety, if survival results achieved with it are commensurate with those achieved with repeat hepatectomy.
Although it is very appealing, percutaneous RF ablation has intrinsic drawbacks. RF ablation cannot be used in HCC tumors that are located too close to the major hepatic vessels (15–17,30,34). In addition, the use of image-guided tumor ablation techniques such as RF ablation involves a higher risk of incomplete tumor destruction than that involved in surgical resection (15–17,30,34). In our study, follow-up images of 11 (21%) of 53 HCC tumors showed either residual unablated tumor tissue or local tumor progression after the first RF ablation. However, with prompt and appropriate follow-up measures, including evaluation with CT, incomplete local treatment can be detected early and corrected with additional RF ablation (15–17,23).
Investigators in an earlier study of the use of repeat hepatectomy for recurrent HCC tumors in a larger patient population reported a 3-year survival rate of 56% (6), which is similar to the survival rate (54%) obtained for RF ablation in our study. However, we cannot directly compare these 3-year survival rates with that obtained at our institution after repeat hepatectomy for intrahepatic HCC recurrence, because fewer than 10 patients underwent repeat hepatectomy at our institution. The use of RF ablation has substantially replaced that of repeat hepatectomy at our institution, and it is not easy to recruit patients for a randomized controlled study comparing RF ablation and repeat hepatectomy—even patients who have resectable small recurrent HCC tumors.
In addition to repeat hepatectomy, TACE, PEIT, and systemic chemotherapy have been used, occasionally in combination, to treat intrahepatic recurrent HCC after surgical resection. The results of our study suggest that RF ablation is an effective and safe alternative for treating recurrent HCC after hepatectomy if repeat hepatectomy is not feasible. We believe that even in patients in whom repeat hepatectomy is feasible, RF ablation is a promising alternative to repeat hepatectomy if the number, size, and location of recurrent tumors allow ablation to be performed safely.
This study had some limitations. First, only patients who underwent percutaneous RF ablation for recurrent HCC were included. Moreover, because the hepatologists at our institution have a thorough knowledge of the indications for percutaneous RF ablation in patients with liver cancer and they themselves make the appropriate referrals of such patients after triage according to our indications, we do not know how many patients with recurrent HCC after hepatectomy were excluded from the study group by hepatologists. The retrospective nature of this study made it difficult to ascertain the number of patients referred for RF ablation in whom percutaneous RF ablation was considered unfeasible because of the tumor location. We plan to conduct a prospective study to address these limitations.
In conclusion, our current study results show a high rate of successful treatment and good survival rates with percutaneous RF ablation of recurrent HCC tumors after hepatectomy. Although further studies in a larger population of patients are needed to clarify the place of RF ablation among treatments for recurrent HCC, the results of our study suggest that percutaneous RF ablation should be considered as the initial therapy for recurrent HCC tumors that are not treatable with repeat hepatectomy. Our results also indicate that follow-up CT performed at regular intervals after RF ablation in patients with recurrent HCC can enhance the results of ablation and ensure early detection of further recurrence.
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FOOTNOTES |
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Author contributions: Guarantors of integrity of entire study, H.K.L., D.C.; study concepts, H.K.L.; study design, H.K.L., D.C.; literature research, D.C.; clinical studies, H.K.L., D.C., M.J.K., S.H.K., J.H.L., J.W.J., Y.I.K.; data acquisition, S.H.L., D.C.; data analysis/interpretation, H.K.L., D.C.; statistical analysis, S.H.L., D.C.; manuscript preparation, D.C.; manuscript definition of intellectual content and manuscript editing, H.K.L.; manuscript revision/review, H.K.L., W.J.L.; manuscript final version approval, H.K.L.
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REFERENCES |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODS RESULTSDISCUSSIONREFERENCES |
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