Radiofrequency ablation versus ethanol injection for early hepatocellular carcinoma: A randomized controlled trial

Objective. To compare percutaneous ethanol injection (PEI), the standard approach which has been used for many years to treat early non-surgical hepatocellular carcinoma (HCC) in cirrhotic patients, and radiofrequency ablation (RFA), which has become an interesting alternative. Material and methods. A randomized trial was carried out on 139 cirrhotic patients in Child-Pugh classes A/B with 1–3 nodes of HCC (diameter 15–30 mm), for a total of 177 lesions. Patients were randomized to receive RFA (n=70) or PEI (n=69). The primary end-point was complete response (CR) 1 year after the percutaneous ablation of all HCC nodes identified at baseline. Secondary end-points were: early (30–50 days) CR, complications, survival and costs. Results. In an intention-to-treat analysis, 1-year CR was achieved in 46/70 (65.7%) and in 25/69 (36.2%) patients treated by RFA and PEI, respectively (p=0.0005). For lesions >20 mm in diameter, there was a larger CR rate in the RFA group (68.1% versus 26.3%). An early CR was obtained in 67/70 (95.7%) patients treated by RFA compared with 42/64 (65.6%) patients treated by PEI (p=0.0001). Complications occurred in 10 and 12 patients treated by RFA and PEI, respectively. The overall survival rate was not significantly different in the RFA versus PEI arm (adjusted hazard ratio=0.88, 95% CI: 0.50–1.53). There was an incremental health-care cost of 8286 € for each additional patient successfully treated by RFA. Conclusions. The 1-year CR rate after percutaneous treatment of early HCC was significantly better with RFA than with PEI but did not provide a clear survival advantage in cirrhotic patients.     

Radiofrequency ablation therapy for hepatocellular carcinoma in elderly patients

Background and Aim: With the aging of society, the number of elderly patients with hepatocellular carcinoma (HCC) has been increasing in Japan. The Government of Japan defines elderly as being over 65 and has divided the elderly into two stages: the first elderly stage (< 75 years old) and the second elderly stage (≥ 75). We investigated the efficacy and safety of radiofrequency ablation therapy (RFA) in patients in the second elderly stage in comparison with other HCC patients, retrospectively. Methods: Two hundred six patients with HCC, who were within the Milan criteria, with low‐grade performance status (0 or 1) and a Child‐Pugh classification of A or B were enrolled. All were treated with RFA from January 2000 to December 2008 as an initial therapy and were divided into elderly HCC group (e‐HCC group; ≥ 75, n = 63) and non e‐HCC group (< 75, n = 143), and their clinical data and survival rates were compared. Results: Age and the level of protein induced by vitamin K absence or antagonist (PIVKA‐II) were higher in the e‐HCC group as compared with the non e‐HCC group (78.3 ± 3.2 vs 64.2 ± 7.5 years, 676.3 ± 2643.7 vs 142.4 ± 442.2 mAU/mL: P < 0.01, respectively). There were no significant differences for Child‐Pugh class, tumor node metastasis stage, and Japan Integrated Stage score and in survival rates after 3, and 5 years between the groups (e‐HCC group: 82.5% and 49.7%, respectively; non e‐HCC group: 78.3% and 57.5%, respectively). There were no severe complications in the e‐HCC group. Conclusions: Elderly HCC patients, who have good performance status, should be treated in the same manner and with the same strategy as young HCC patients.     

Efficacy and safety of radiofrequency ablation versus laparoscopic hepatectomy for small hepatocellular carcinoma: A protocol for a randomized controlled trial

Background:Hepatocellular carcinoma (HCC) is one of the most common type of malignant tumors in adults, and is the most common cause of death in people with cirrhosis. Both laparoscopic hepatectomy (LH) and radiofrequency ablation (RFA) are radical treatments for small HCC. However, there is no international standard for the treatment of small HCC, and it is still controversial to choose LH or RFA in treating small HCC. We try to carry out a randomized, controlled, prospective study to compare the the short-term and long-term effects and safety of LH versus RFA in the treatment of small HCC.Methods:This study is a single-center, evaluator-blinded, randomized, controlled clinical trial (RCT). The patients will be randomly divided into RFA group and LH group in a 1:1 ratio according to a computer-generated randomization list. Postoperative complications rates, Alpha fetoprotein (AFP), hospital stay, 1, 2, 3-year overall survival (OS) rates, disease-free survival (DFS) rates and all possible adverse events will be recorded. Statistical analyses will be performed with SPSS v22.0 software.Conclusions:The study will compare the the short-term and long-term effects and safety of LH versus RFA in the treatment of small HCC.OSF Registration number:doi: 10.17605/OSF.IO/HNX2T     

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.     

Radiofrequency ablation versus surgical resection as primary treatment of hepatocellular carcinoma meeting the Milan criteria: a systematic review

Background and Aim: Surgery is the standard treatment option for hepatocellular carcinoma (HCC) meeting the Milan criteria, defined as single HCC ≤ 5 cm in maximum diameter or up to three nodules ≤ 3 cm. However, favorable survival outcomes have also been reported for these HCCs following radiofrequency ablation (RFA). Methods: We performed a systematic review to compare the results of hepatic resection and percutaneous RFA as a primary treatment option of HCC meeting the Milan criteria. Studies were identified by searching MEDLINE on PubMed, the Cochrane Library database and CANCERLIT using appropriate key words. Results: In all six identified observational studies, there were no statistically significant differences in overall survival rates between the two treatment modalities. The results of two randomized trials are controversial, while the power of these randomized trials is too limited to reach a reliable conclusion. In practice, the choice of treatment between surgery and RFA largely depends on the relationship between the local recurrence and perioperative mortality rates of HCC patients. Following RFA, local recurrence rates are low when a minimal safety margin ≥ 4–5 mm is achieved. A previous simulation study of overall survival for very early stage HCC, defined as an asymptomatic solitary small HCC ≤ 2 cm, showed that primary RFA with a 9% local recurrence rate is comparable to surgical resection with a 3% operative mortality rate. Conclusion: Acquisition of a sufficient safety margin seems to be a critical factor before recommending wider application of RFA as primary treatment for HCCs that meet the Milan criteria.     

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.     

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.     

射频消融对比手术切除治疗小肝癌的Meta分析

目的:比较射频消融术与外科手术切除在治疗小肝癌中的疗效.方法:计算机检索1991-2011年发表的有关采用射频消融术(radiofrequency ablation,RFA)与外科手术肝切除(surgical hepatic resection,HR)治疗小肝癌的对照试验,按照Cochrane系统评价员手册4.2.2版所推荐的质量评价标准来筛选试验,评价纳入研究的方法学质量,用RevMan5.0.25版软件对研究进行系统评价及Meta分析.结果:共纳入2个随机对照试验,9个非随机对照试验,其中英文9篇,中文1篇,韩文1篇.所纳入的研究共包括2965例患者:其中射频消融组患者1459例、外科手术切除组患者1506例.Meta分析表明:外科手术组在3年、5年生存率及1、3、5年无瘤生存率上明显高于射频消融组,差异均有统计学意义(P<0.05),两者1年生存率相比无显著差异(P>0.05);术后严重并发症射频消融组明显低于外科手术组(P<0.05).结论:现有的证据表明,对于小肝癌,射频消融术后严重并发症明显少于外科手术切除,但是外科手术切除治疗小肝癌总体疗效仍明显优于射频消融治疗.     

Radiofrequency ablation versus surgical resection for single nodule hepatocellular carcinoma: Long-term outcomes

Background. Radiofrequency ablation (RFA) has been increasingly utilized for treatment of hepatocellular carcinoma (HCC). Long-term results of RFA, especially in comparison to surgical resection, have not been well described.Methods. Eighty-seven patients with single nodule HCC underwent surgical resection (N=47) or RFA (N=40) during a 9-year period. RFA was performed for 36 unresectable disease and 4 surgical refusals. Each group was further divided based on tumor size for analysis; Group 1: resection, ≤5 cm (N=18), Group 2: RFA, ≤5 cm (N=26), Group 3: resection, >5 cm (N=29) and Group 4: RFA, >5 cm (N=14). Follow-up ranged from 2 to 72 months (median 16 months). Patients'' characteristics, local recurrences and overall and disease-free survivals were compared.Results. Patients who underwent RFA were older (69 versus 60, p=0.0006), had more advanced Child-Pugh class and TNM stage (p=0.0002 and p=0.016, respectively), and had smaller tumors (4.6 versus 7.4 cm, p=0.0032). Local recurrence rates were 2% for resection and 10% for RFA (p=0.12). These local and other recurrences were subsequently treated with multimodal therapies as indicated. The median overall and disease-free survivals were equivalent both between Groups 1 and 2 (49 versus 51 months, p=0.44, 36 versus 22 months, p=0.84), and Groups 3 and 4 (47 versus 463 months, p=0.94, 28 versus 20 months, p=0.67).Discussion. Although the groups were not truly comparable, this retrospective study suggests that RFA may offer similar long-term results to surgical resection for single nodule HCC when combined with multimodal treatments.     

Percutaneous microwave and radiofrequency ablation for hepatocellular carcinoma: a retrospective comparative study

Background Percutaneous microwave ablation and radiofrequency ablation are two commonly used modalities for the treatment of hepatocellular carcinoma; however, comparisons of them have not been documented adequately. Methods Of 102 patients with biopsy-proved hepatocellular carcinoma, 49 (98 nodules) were treated percutaneously with microwave ablation and 53 (72 nodules) with radiofrequency ablation. The local tumor control, complications related to treatment, and long-term results of the two modalities were compared retrospectively. Results The complete ablation rates were 94.9% (93/98) using microwave ablation vs 93.1% (67/72) using radiofrequency ablation (P = 0.75), and no significant differences were found either in the ablation of tumors of 3.0 cm or less (P = 1.00) or in those of more than 3.0 cm (P = 1.00) between the two modalities. The local recurrence rates were 11.8% (11/93) using microwave ablation vs 20.9% (14/67) using radiofrequency ablation (P = 0.12), and there were no significant differences between the two modalities either in tumors of 3.0 cm or less (P = 0.36) or in those of more than 3.0 cm (P = 0.82). The rates of major complications associated with microwave ablation and radiofrequency ablation were 8.2% (4/49) vs 5.7% (3/53; P = 0.71). The disease-free survival rates in the microwave ablation group were 45.9%, 26.9%, 26.9%, and 13.4% at 1, 2, 3, and 4 years, respectively, and those in the radiofrequency ablation group were 37.2%, 20.7%, and 15.5% at 1, 2 and 3 years, respectively (P = 0.53). The 1-, 2-, 3-, and 4-year cumulative survival rates for patients who underwent microwave ablation were 81.6%, 61.2%, 50.5%, and 36.8%, respectively, and for patients who underwent radiofrequency ablation the rates were 71.7%, 47.2%, 37.6%, and 24.2%, respectively (P = 0.12). Conclusions Percutaneous microwave ablation and radiofrequency ablation are both effective methods in treating hepatocellular carcinomas. The local tumor control, complications related to treatment, and long-term survivals were equivalent for the two modalities.     

Radiofrequency ablation in the treatment of small hepatocellular carcinoma: A meta analysis

AIM:To evaluate survival and recurrence after radiofrequency ablation(RFA) for the treatment of small hepatocellular carcinoma(HCC) using a meta-analysis.METHODS:Literature on RFA vs surgical resection for the treatment of small HCC published between January 1990 and December 2008 was retrieved.A metaanalysis was conducted to estimate pooled survival and recurrence ratios.A fixed or random effect model was established to collect the data.RESULTS:The differences in overall survival at 1-year,3-years and at e...     

手术切除与射频消融治疗小肝癌的疗效比较

目的比较小肝癌手术切除与射频消融（RFA）初治后疗效及复发情况。方法收集吉林大学白求恩第一医院2002年1月至2008年12月接受手术或RFA初治的97例小肝癌患者资料,并对治疗后满2年的患者进行随访,共随访到63例,手术和RFA治疗分别为34和29例,回顾性分析两种方法治疗小肝癌患者的预后复发情况。计量资料采用χ2检验,利用Cox回归分析比较影响患者复发相关的危险因素,并应用Log-rank进行两种无瘤生存率检验。结果手术与射频消融治疗小肝癌3个月、1、2 a复发率分别15%、38%、64%,21%、35%、45%,两者差异无统计学意义。初治后复发与治疗方法、性别、年龄、Child-Pugh分级、肿瘤大小、结节数目、是否合并有肝硬化、甲胎蛋白水平相关性差异无统计学意义,两者无瘤生存率差异无统计学意义。结论 RFA与肝癌切除术在治疗小肝癌取得相近的治疗效果,RFA有望成为替代手术治疗的一种理想的治疗方法。     

Predisposing factors for recurrence of HBV-related small hepatocellular carcinoma after percutaneous radiofrequency ablation

Abstract

Background. Radiofrequency ablation (RFA) as a curative therapy for hepatocellular carcinoma (HCC) is widely used. The aim of this study was to investigate predisposing factors for HCC recurrence in patients with hepatitis B virus (HBV)-related small HCC after RFA. Methods. A total of 170 patients underwent percutaneous RFA for HBV-related small HCC (≤3 cm in diameter) from January 2008 to December 2010 at Samsung Medical Center. We analyzed the risk factors for recurrence of HCC after RFA. Results. The median follow-up duration was 27.0 months. A total of 89 patients (52%) experienced recurrence after percutaneous RFA. Cumulative recurrence-free rates after RFA at 1-, 3-, and 5 years were 81.3%, 47.2% and 35.7%, respectively. Univariate analysis showed that predisposing factors for HCC recurrence were the multinodularity (hazard ratio (HR) 2.22, p = 0.005), pre-RFA HBV DNA levels ≥2000 IU/mL (HR 1.61, p = 0.025), and Barcelona Clinic Liver Cancer stage A (HR 1.54, p = 0.046). The independent risk factors for recurrence by multivariate analysis were the multinodularity (HR 1.94, p = 0.026) and pre-RFA HBV DNA levels ≥2000 IU/mL (HR 1.57, p = 0.039). Conclusion. Multinodularity and HBV DNA levels were associated with the recurrence of HBV-related small HCC after RFA.     

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.     

Radiofrequency ablation of hepatocellular carcinoma as a bridge to liver transplantation

Background

Radiofrequency ablation (RFA) of hepatocellular carcinoma (HCC) is widely utilized as a bridge to liver transplant with limited evidence to support efficacy. The purpose of the present study was to measure the effect of RFA on time to drop-off in HCC-listed patients.

Methods

Patients with Milan criteria tumours listed between January 1999 and June 2007 were stratified into RFA (n = 77) and No Treatment groups (n = 93).

Results

The primary effectiveness of RFA was 83% (complete radiographic response). RFA was associated with a longer median wait time to transplant (9.5 vs. 5 months). Tumour-specific drop-off events were equivalent between RFA (21%) and No Treatment (12%) groups (P = 0.11). Controlling for wait time, there was no difference in overall (P = 0.56) or tumour-specific drop-off (P = 0.94). Furthermore, there were no differences in 5-year overall or tumour-free survivals from list date or transplant. Using multivariate analysis, the likelihood of receiving a transplant and patient survivals were associated with tumour characteristics (AFP, tumour number and size) and not with bridge therapy or waiting time.

Discussion

RFA allows patients to be maintained longer on the waiting list without negative consequences on drop-off or survival compared with no treatment. Post-transplant outcomes are affected more by tumour characteristics than RFA or wait time.     

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,