Efficacy and safety of microwave ablation and radiofrequency ablation in the treatment of hepatocellular carcinoma: A systematic review and meta-analysis

Background:Hepatocellular carcinoma (HCC) is one of the most common malignant tumors. Surgical resection is often only possible in the early stages of HCC and among those with limited cirrhosis. Radiofrequency ablation and Microwave ablation are 2 main types of percutaneous thermal ablation for the treatment of HCC. The efficacy and safety between these 2 therapy methods are still under a debate.Objective:To compare the efficacy and safety of Radiofrequency ablation and Microwave ablation in treating HCC.Methods:PubMed, EMBASE, the Cochrane databases and Web of Science were systematically searched. We included randomized controlled trials and cohort studies comparing the efficacy and safety of Radiofrequency ablation and Microwave ablation in HCC patients. Outcome measures on local tumor progression, complete ablation, disease-free survival, overall survival, or major complications were compared between the 2 groups. The random effect model was used when there was significant heterogeneity between studies, otherwise the fixed effect model was used.Results:A total of 33 studies, involving a total of 4589 patients were identified, which included studies comprised 7 RCTs, 24 retrospective observational trials, and 2 prospective observational trial. Microwave ablation had a lower local tumor progression than Radiofrequency ablation in cohort studies (OR = 0.78, 95% CI 0.64–0.96, P = .02). Complete ablation rate of Microwave ablation was higher than that of Radiofrequency ablation in cohort studies (OR = 1.54, 95% CI 1.05–2.25, P = .03). There was no significant difference in overall survival and disease-free survival between the 2 groups. Meta-analysis showed that there was no significant difference in the main complications between Microwave ablation and Radiofrequency ablation.Conclusions:Microwave ablation has higher complete ablation and lower local tumor progression than Radiofrequency ablation in the ablation treatment of HCC nodules. There was no significant difference in overall survival between the 2 therapy methods.     

Percutaneous ablation for small hepatocellular carcinoma

Hepatocellular carcinoma is increasingly detected at small size, usually 5 cm or smaller in diameter. For small hepatocellular carcinoma, percutaneous ablation is a potentially curative treatment. Ethanol injection is able to achieve a complete response of 70–80% and a 5-year survival of 40–60% in the treatment of hepatocellular carcinoma of 3 cm or less. Radiofrequency ablation has emerged as the more powerful alternative method. Randomized controlled trials show that radiofrequency ablation offers a higher complete response at fewer treatment sessions and better survival compared with ethanol injection. Microwave ablation has been demonstrated to be equivalent to radiofrequency ablation in both local efficacy and long-term outcome. Laser ablation is mainly applied in clinical settings in Europe. Nowadays, percutaneous ablation is commonly accepted as the best option for patients with small hepatocellular carcinoma who are not candidates for surgical resection or liver transplantation. However, whether it can compete with surgery as the first-line treatment has long been debated. There are some retrospective studies and only a few randomized controlled trials to compare the two modalities. The currently available data are not robust enough to draw a solid conclusion. This review article provides an overview of the current status of percutaneous ablation in management of small hepatocellular carcinoma and also focuses on comparison with surgical resection.     

射频消融联合索拉非尼治疗进展期肝细胞癌的临床观察

原发性肝癌在全球发病率已超过62.6万/年,居于恶性肿瘤发病率的第5位;病死率也接近60万/年,位居肿瘤相关死亡的第3位[1]。我国发病人数约占全球的55%,其中85%～90%为肝细胞癌,     

Efficacy and long‐term outcome of laparoscopic microwave coagulation or radiofrequency ablation therapy for surface‐type hepatocellular carcinoma

Background: Microwave or radiofrequency ablation therapy has been widely perfomed for hepatocellular carcinoma (HCC). Whereas ablation therapy is effective treatment, it cannot be perfomed easily, as is evident in several reports of severe complications. We treated surface‐type HCC under laparoscopy in avoidance of complications from March 1996. In the present study, we examined the efficacy and long‐term outcome of laparoscopic ablation therapy. Patients and Methods: The patients were 47 cases (58 lesions) of HCC treated by laparoscopic ablation therapy under general anesthesia in our Center from March 1996 until March 2003. Results: The surface‐type HCC to which the therapy was applicable accounted for approximately 15% of all cases. The overall 5‐year survival rate was 62%. Hepatic reserve and rate of intrahepatic recurrences in the remnant liver after curative treatment were the limiting factors on the survival rate. There was no serious complication in the treatment. It was well tolerated and brought about good quality of life. Conclusion: Laparoscopic ablation therapy was considered to be an easy and effective approach, and its utility was also recognized in the avoidance of the problems of percutaneous treatment, such as bleeding or damage to the adjacent organs.     

高龄原发性肝癌射频治疗疗效分析

目的观察高龄原发性肝细胞癌(HCC)患者射频消融治疗(RFA)疗效及RFA对肝功能及生命质量的影响.方法超声引导RFA治疗的225例HCC患者为本文研究对象;非老年组(年龄≤60岁)109例;老年组(年龄＞60岁)116例中,年龄≥70岁者50例,52.6%(61人)合并其他疾病.治疗前两组病灶大小,肝功能分级均无显著差异.比较两组RFA疗效、生存期、生存率、生命质量变化及对肝功能的影响.结果两组消融成功率,局部肿瘤进展率均无明显差异.平均生存期非老年组为(43.31±3.16)个月,老年组为(41.07±2.50)个月,两组无统计学差异.老年组RFA治疗前后生命质量得分无显著差异;治疗后,老年组社会功能领域得分高于非老年组,两组生命质量总得分及其他领域得分均无显著差异.两组患者治疗前与治疗后1个月的谷丙转氨酶、谷草转氨酶、总胆红素水平均无明显差异.结论RFA对不适合手术治疗的高龄HCC患者,可获得良好疗效,并保持患者较高的生命质量;对高龄患者可作为首选治疗方法之一.     

Percutaneous ultrasound-guided radiofrequency ablation with artificial pleural effusion for hepatocellular carcinoma in the hepatic dome

Background Nodules of hepatocellular carcinoma (HCC) located in the hepatic dome cannot be depicted on ultrasography because of pulmonary air. Therefore, percutaneous treatment is not possible in such cases. The purpose of this study was to clarify the feasibility and safety of percutaneous sonographically guided radiofrequency (RF) ablation with the concurrent use of artificial pleural effusion for HCC located in the right subphrenic region.Methods Between May 2001 and June 2002, 24 patients with 28 HCC nodules located directly below the diaphragm were enrolled in this study. The patient population included 17 men and 7 women (age range, 51–87 years; mean age, 66.5 years). The maximum diameter of the HCC nodules ranged from 1.0cm to 4cm (mean ± SD, 2.1 ± 0.8cm).Results We infused 200–1100ml of 5% glucose solution intrathoracically to separate the lung and liver; thus, obtaining an image of the whole tumor was impossible on gray-scale sonography. Complete tumor necrosis was achieved in a single session of RF ablation in 27 (96.4%) of the 28 lesions, while two sessions of RF ablation were required for the remaining lesion (3.6%). During treatment, no dyspnea or other complications concerned with the respiratory system were observed. Clinical courses have been satisfactory without recurrences at 1–13 months after treatment (mean, 7.9 months).Conclusions Percutaneous RF ablation with artificial pleural effusion in patients with HCC in the hepatic dome may be a safe and feasible therapy.     

Laparoscopic repair of iatrogenic diaphragmatic hernia following radiofrequency ablation for hepatocellular carcinoma

Radiofrequency ablation (RFA) is commonly used for treating unresectable hepatic malignancies. Some commonly associated complications of RFA include fever, symptomatic pleural effusion, abscess, hepatoma and hepatic insufficiency. Here, we report a case of diaphragmatic hernia in a patient following RFA for hepatic malignancy with cirrhosis.     

Efficacy and safety of radiofrequency ablation for elderly hepatocellular carcinoma patients

Aim: This study was conducted to evaluate the efficacy and safety of radiofrequency ablation (RFA) therapy in elderly patients with hepatocellular carcinoma (HCC). Methods: Four hundred and sixty‐one patients with naïve HCC, including 107 elderly (aged ≥75 years) patients, who were treated with RFA between 2000 and 2007, were enrolled. Baseline characteristics, survival/recurrence rates and complications after RFA were compared between elderly and non‐elderly patients. Results: In the elderly group, the proportion of men, alcohol consumption, serum alanine aminotransferase and γ‐glutamyl transpeptidase levels were significantly lower compared with those in the non‐elderly group. There were no differences in Child–Pugh grade and tumor characteristics between the two groups. The cumulative survival rates in the elderly group were 82% at 3 years and 61% at 5 years, which was equivalent to the non‐elderly group. Similarly, no differences were observed in recurrence rates. In multivariate analysis, Child–Pugh grade and tumor‐related factors were significant factors associated with survival, but age was not. Although elderly patients had more extrahepatic comorbidities, their presence was not a factor associated with survival prognosis or complication after RFA. Conclusion: RFA treatment might be safe and effective in elderly patients, as well as non‐elderly patients, with HCC.     

Clinical features and risk factors of extrahepatic seeding after percutaneous radiofrequency ablation for hepatocellular carcinoma

Aim: To clarify the clinical features of and risk factors for extrahepatic seeding, a major complication following radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC). Methods: Our prospective database of 351 nodules in 257 patients with HCC who had undergone RFA between April 2001 and April 2008 was reviewed. The following variables were assessed to identify the risk factors for extrahepatic seeding: age, sex, viral markers, Child–Pugh class, tumor size, number of tumors, RFA indication (tumor size ≤3 cm, number of tumors ≤3), tumor biopsy prior to RFA, degree of histological differentiation, tumor markers, tumor location, number of sessions, and combined transcatheter arterial chemoembolization. Results: The median follow‐up period was 36.5 months, during which the rate of seeding after was 5.1% and the 5‐year cumulative seeding rate was 8.4%. The survival rate after neoplastic seeding was 21% at 5 years. Univariate analysis of the risk factors for neoplastic seeding showed significant differences in tumor size, RFA indication, subcapsular lesion, number of sessions, tumor biopsy prior to RFA, and des‐gamma‐carboxy prothrombin value. However, multivariate analysis showed that the only independent risk factor was RFA indication. Conclusions: The prognosis of patients with neoplastic seeding was poor. In particular, RFA performed for HCC not satisfying the RFA indication showed a high risk of seeding, and careful consideration should be given to the optimal treatment method and avoiding direct puncture of subcapsular tumors.     

Clinical outcomes of radiofrequency ablation and surgical resection for small hepatocellular carcinoma: a meta-analysis

Background and Aim: To evaluate the evidence comparing radiofrequency ablation (RFA) and surgical resection (RES) on the treatment of hepatocellular carcinoma (HCC) using meta‐analytical techniques. Methods: Literature search was undertaken until March 2011 to identify comparative studies evaluating survival rates, recurrence rates, and complications. Pooled odds ratios (OR) and 95% confidence intervals (95% CI) were calculated with either the fixed or random effect model. Results: These studies included a total of 877 patients: 441 treated with RFA and 436 treated with RES. The overall survival was significantly higher in patients treated with RES than RFA at 1, 3 and 5 years (respectively: OR: 0.50, 95% CI: 0.29–0.86; OR: 0.51, 95% CI: 0.28–0.94; OR: 0.62, 95% CI: 0.45–0.84). In the RES group the 1, 3, and 5 years recurrence‐free survival rates were significantly higher than the RFA group (respectively: OR: 0.65, 95% CI: 0.44–0.97; OR: 0.65, 95% CI: 0.47–0.89; OR: 0.52, 95% CI: 0.35–0.77). RFA had a higher rate of local recurrence (OR: 4.08, 95% CI: 2.03–8.20). For tumors ≤ 3 cm RES was better than RFA in the 3‐year overall survival rates (OR: 0.38, 95% CI: 0.16–0.89). Conclusions: Surgical resection was superior to RFA in the treatment of HCC. However, the findings have to be carefully interpreted due to the lower level of evidence.     

Intraoperative radiofrequency ablation with or without tumorectomy for hepatocellular carcinoma in locations difficult for a percutaneous approach

BACKGROUND:Although hepatic resection is widely accepted as a proper modality for treating hepatocellular carcinoma(HCC),a majority of patients are unable to undergo surgical resection due to various tumor and patient factors.Radiofrequency ablation(RFA)has mostly been used as a therapeutic alternative to resection for treating HCC.The objective of this study was to evaluate the results of intraoperative RFA for HCCs in locations difficult for a percutaneous approach.METHODS:Eight patients(male,seven;age,49...     

Endoscopic thermal ablation therapies for hepatocellular carcinoma: a multi-center study

Aim:  The differing efficacies of radiofrequency ablation and microwave coagulation for hepatocellular carcinoma (HCC) are unknown. Therefore, we performed a multi-center study to assess the factors contributing to survival and local recurrences of HCC among patients with solitary tumors who underwent endoscopic thermal ablation as their primary treatment.
Methods:  From six institutions, 391 patients with solitary HCC who were first treated by endoscopic thermal ablation were enrolled in this study and assessed retrospectively. We investigated age, gender, location of tumor, longest diameter of tumor, method of anesthesia, type of endoscope, method of thermal ablation, Child–Pugh classification, the Japan Integrated Staging score and the Cancer of the Liver Italian Program score. Statistical analyses were performed using univariate analysis with log–rank test and multivariate analysis with the Cox proportional hazards model.
Results:  On univariate analysis, advanced Child–Pugh score, advanced Italian Program score and local recurrences were significant predictors of poor survival. Young age (≤70), large tumor (>30 mm) and the use of the thoracoscopic approach were significant predictors for the development of local recurrence. On multivariate analysis, local anesthesia and advanced Child–Pugh score were independent predictors of poor survival. Young age, large tumor, local anesthesia and the use of the thoracoscopic approach were independent predictors for the development of local recurrence. The method of thermal ablation did not influence survival or local recurrence.
Conclusions:  Differences in the effect on survival and local recurrence between microwave and radiofrequency were not observed in this retrospective, multi-center study of endoscopic thermal ablation for HCC.     

Percutaneous radiofrequency ablation with cooled electrodes combined with hepatic arterial balloon occlusion in hepatocellular carcinoma

Background We have reported that percutaneous radiofrequency ablation (RFA) with balloon occlusion of the hepatic artery (balloon-occluded RFA), using an expandable electrode, increases the coagulation area. In this study, we investigated the efficacy of balloon-occluded RFA and balloon-microcatheter-occluded RFA, using a cool RF single electrode.Methods We studies 41 patients with 47 hepatocellular carcinoma (HCC) lesions. We treated 28 patients (32 nodules) with balloon-occluded RFA, 5 patients (6 nodules) with balloon-microcatheter-occluded RFA, and 8 patients (9 nodules) with standard RFA. Initial therapeutic efficacy was evaluated with dynamic computed tomography performed 1 week after one session of treatment.Results One session of treatment was done for 20 nodules (62.5%) in the balloon-occluded RFA group and for 4 nodules (66.7%) in the balloon-microcatheter-occluded RFA group. We compared the coagulation diameter for balloon-occluded RFA (7 nodules), balloon-microcatheter-occluded RFA (6 nodules), and standard RFA (9 nodules) after one application cycle (12min). The greatest dimension of the area coagulated by balloon-occluded RFA was significantly larger (greatest long-axis dimension, 47.6 ± 7.8mm; greatest short-axis dimension, 33.4 ± 7.5mm) than that coagulated by standard RFA (greatest long-axis dimension, 35.3 ± 4.7mm; greatest short-axis dimension, 25.9 ± 3.7mm; P = 0.002 for greatest long-axis dimension; P = 0.041 for greatest short-axis dimension). However, there was significant difference only in the greatest short-axis dimension of the area coagulated comparing balloon-microcatheter-occluded RFA and standard RFA.Conclusions We consider balloon-occluded RFA using a cool RF electrode to be superior to standard RFA for the treatment of HCC, especially when larger coagulation volumes are required.     

Tolerance of radiofrequency ablation by patients of hepatocellular carcinoma

Background

Radiofrequency ablation (RFA) is currently an effective method for ablation of hepatocellular carcinoma (HCC). Early reports have indicated that RFA is safe and virtually free from major complications. Unlike partial hepatectomy for HCC on patients with cirrhosis, there are no data on the safety limit of RFA. However, information is vital for selection of appropriate patients for the procedure. In this study, we analyzed results from use of RFA on HCC patients and determined the lower limit of liver function with which HCC patients can tolerate RFA.

Method

Preoperative variables of 310 patients who underwent RFA for HCC were analyzed to identify the risk factors in RFA intolerance in terms of morbidity associated with stress-induced complications.

Results

Thirty-nine (12.6%) patients developed intolerance of RFA. Postoperative morbidity was mainly because of intractable ascites (n = 13), hyperbilirubinemia (n = 10), massive pleural effusion (n = 7), and other complications (n = 14). Multivariate analysis revealed that serum albumin level (P = 0.001), serum bilirubin level (P = 0.000), tumor number (P = 0.002), and RFA duration (P = 0.017) all played a role in this issue.

Conclusions

Simple data such as serum bilirubin, serum albumin level, and tumor number can be used to predict HCC patients’ tolerance of RFA. Avoidance of excessive RFA time and careful monitoring of patients at risk are important means of reducing the postoperative morbidity rate.     

Recurrent hepatocellular carcinoma successfully treated with radiofrequency thermal ablation

We report a patient with hepatocellular carcinoma (HCC) who was successfully treated with radiofrequency thermal ablation (RFA). A 71-year-old man was admitted to our hospital in August 1996 with recurrence of HCC. Partial hepatic resection had been performed in January 1993 for HCC that had measured 1.3 cm in segment VIII, and subsequently he had received six sessions of percutaneous ethanol injection (PEI) for treatment of recurrence. Dynamic computed tomography (CT) performed in August 1996 showed two recurrent tumors, one measuring 3.8 cm in segment VIII adjacent to the right hepatic vein, and one measuring 2.0 cm in segment V. Three sessions of percutaneous RFA were performed. After this treatment, most of the tumor in segment VIII and all the tumor in segment V showed low density on dynamic CT, and the right hepatic vein was preserved. However, a remnant of the mass appeared near the right hepatic vein 2 months after the treatment. An additional two sessions of RFA were performed. After the end of treatment, serum alpha-fetoprotein level dropped to the normal range, and no sign of recurrence has been observed until September 1998.     

Utility of contrast-enhanced ultrasonography with Sonazoid in radiofrequency ablation for hepatocellular carcinoma

Background and Aims: Kupffer imaging in contrast‐enhanced ultrasonography (CEUS) with Sonazoid, which lasts for 60 min or longer, may be useful in ultrasound‐guided percutaneous tumor ablation. The utility of Sonazoid in radiofrequency ablation (RFA) of hepatocellular carcinoma (HCC) was investigated in this study. Methods: We analyzed a total of 716 HCC nodules that were detected on dynamic computed tomography in 316 patients. Detectability of these nodules was compared between CEUS and conventional ultrasonography. The effectiveness in the treatment was assessed by comparing the mean numbers of treatment sessions of RFA in patients treated with CEUS and that in historical controls matched for tumor and background conditions. Results: Detectability of tumor nodule was 83.5% in conventional ultrasonography and 93.2% in CEUS (P = 0.04). Sixty‐nine nodules in 52 patients were additionally detected with CEUS. The number of additionally detected tumor nodules was positively correlated with serum albumin level (P = 0.016). The number of RFA sessions was 1.33 ± 0.45 with CEUS as compared to 1.49 ± 0.76 in the historical controls (P = 0.0019). Conclusions: CEUS with Sonazoid is useful for HCC detection in patients with a well‐conserved liver function reservoir. The decrease in RFA session numbers indicated the utility of Sonazoid in RFA treatment of HCC.