Insufficient radiofrequency ablation therapy may induce further malignant transformation of hepatocellular carcinoma

Background Radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC) is a thermoablative technique to kill tumor tissue by generating areas of coagulative necrosis. Recent reports have raised concern that RFA may lead to a local recurrence of HCC with an aggressive phenotype and unfavorable prognosis, suggesting that RFA may induce further malignant transformation of HCC. However, the biological effects of RFA on HCC cells have not been directly analyzed. The aim of this study was to determine whether heat stress of the type associated with RFA induces malignant transformation of HCC. Methods We assessed the sensitivity of three HCC cell lines (HepG2, Alexander, and Huh7) to heat treatment for 10 min. We then determined the temperature at which a heat-resistant subline can be generated. We established and expanded sublines that survived heat treatment. And their proliferation rates, heat sensitivities, and invasive capacities were further examined. Results All HepG2 died after 48°C treatment, whereas 49°C treatment was required to kill all Alexander and HuH7. We generated 20 sublines for each parental cell line. A HepG2 subline, HepG2#18, proliferated 100% faster than parental HepG2. Moreover, HepG2#18 survived after 50°C treatment, whereas all parental HepG2 died after heat treatments at 48°C or higher. Conclusion Our results showed that even a single heat treatment could induce further transformation of an HCC cell line. Our results suggest that an insufficient treatment of HCC by RFA that enables survival of some cells might induce further malignant transformation in vivo.     

Surgical vs percutaneous radiofrequency ablation for hepatocellular carcinoma in dangerous locations

AIM:To compare the long-term outcome of percutaneous vs surgical radiofrequency ablation(RFA) for hepatocellular carcinoma(HCC) in dangerous locations.METHODS:One hundred and sixty-two patients with HCC in dangerous locations treated with percutaneous or surgical RFA were enrolled in this study.The patients were divided into percutaneous RFA group and surgical RFA group.After the patients were regularly followed up for a long time,their curative rate,hospital stay time,postoperative complications and 5-year...     

肝动脉化疗栓塞联合射频消融治疗大肝癌的疗效评价

目的探讨经导管肝动脉化疗栓塞（transcatheter arterial chemoembolization,TACE）联合射频消融（radiofrequency ablation,RFA）治疗大肝癌的临床应用价值。方法回顾性分析我院2006年4月至2008年7月收治的66例肝细胞癌患者的治疗结果,根据治疗方法分为TACE＋RFA组、TACE组及RFA组,其中19例行RFA联合TACE治疗（TACE＋RFA组）,24例单纯TACE治疗（TACE组）,23例单纯RFA治疗（RFA组）。结果 TACE＋RFA组的肿瘤坏死率达73.68%,明显高于单纯TACE组及单纯RFA组（分别为50.00%,52.17%,P〈0.01,P〈0.05）。局部复发率分别为26.32%、37.50%和30.43%,三组间无显著统计学差异（P〉0.05）。TACE＋RFA组的平均生存期为28.3个月,显著高于TACE组的13.6个月（P〈0.01）和单纯RFA组的21.7个月（P〈0.05）。结论 TACE联合RFA治疗大肝癌与单纯TACE和单纯RFA治疗效果相比,可提高肿瘤坏死率,延长患者生存期。     

Efficacy of combination therapy with transcatheter arterial chemoembolization and radiofrequency ablation for intermediate-stage hepatocellular carcinoma

Abstract

Objectives: Transcatheter arterial chemoembolization (TACE) is the standard therapy for patients with intermediate-stage hepatocellular carcinoma (HCC). This study aimed to determine whether combination therapy with radiofrequency ablation (RFA) and TACE was superior to TACE monotherapy for intermediate-stage HCC and identify cases in which this technique was the most effective.

Materials and methods: We selected patients with intermediate HCC who met the following eligibility criteria: (1) ≥ 20 years of age, (2) receiving initial therapy, (3) ≤7 tumors, and (4) maximum tumor diameter <5?cm. We performed propensity score matching (PSM) using potential confounding factors. We retrospectively compared the cumulative overall survival rate and recurrence-free survival rate between the TACE?+?RFA and TACE groups. Additionally, a sub-group analysis was performed for preoperative factors.

Results: Among the 103 patients, 92 were selected using PSM. The cumulative overall survival rates at 1, 3, and 5 years for the TACE?+?RFA group were 97.4%, 70.4%, and 60.4%, respectively, which were significantly higher than those for the TACE group (92.7%, 55.7%, and 22.8%, respectively, p?=?.045). The recurrence-free survival rates at 0.5, 1, and 2 years for the TACE?+?RFA group were 80.0%, 58.6%, and 33.3%, respectively, which were significantly higher than those for the TACE group (34.5%, 8.8%, and 2.9%, respectively, p?p?=?.036).

Conclusions: The addition of RFA to TACE improved cumulative overall and recurrence-free survival in patients with intermediate-stage HCC, especially in patients with AFP <100.     

Pathophysiology of recurrent hepatocellular carcinoma after radiofrequency ablation

Radiofrequency ablation (RFA) is effective for the local control of hepatocellular carcinoma (HCC), particularly when a patient's liver functional reserve does not allow radical resection. There is controversy regarding the superiority of surgical resection compared with RFA for such patients, particularly those with three or fewer tumors with diameters ≤3 cm. Moreover, HCC often recurs after RFA, and the tumor cells show distinct phenotypic changes. Incomplete ablation accounts for tumor recurrence, and recent studies provide new insights into the biological mechanisms responsible for the pathological changes of HCC after RFA. This review focuses on the roles of epithelial–mesenchymal transition and cancer stemness that are driven by a mechanism that involves microRNA‐mediated upregulation of hypoxia‐inducible factor‐1. The studies reviewed here provide compelling evidence that complete ablation of HCC is required to prevent recurrence and indicate that further research is urgently required to develop a new systematic strategy to prevent tumor recurrence by targeting hypoxia‐inducible factor‐1.     

Computed tomography-guided transpulmonary radiofrequency ablation for hepatocellular carcinoma located in hepatic dome

AIM:To determine the feasibility of performingcomputed tomography(CT)-guided transpulmonaryradiofrequency ablation(RFA)for hepatocellularcarcinoma(HCC)located in the hepatic dome.METHODS:A total of seven patients with HCCcomprising seven nodules located in the hepatic domewere treated from April 2004 to December 2004.CT-guided transpulmonary RFA was performed using acool-tip type electrode(Radionics Company)based ona standardized energy protocol.All tumors located inthe hepatic dome were not detectable by the usualultrasound(US)methods.The lesion diameters rangedfrom 15 to 27 mm.RESULTS:RFA was technically feasible in all thepatients.The puncture procedure was performed twiceor less and the total average performance time was40.6 min.Local tumor control was achieved in all thepatients.The necrosis diameter ranged from 25 to35 mm.The mean follow-up period was 9.6(7-14 mo)mo.There was no local recurrence at the follow-uppoints.Pneumothorax requiring pleural drainage was themain complication,which was observed in two of theseven patients(28.6%).However,it improved with chestdrainage tube,and the tube could be removed within2-3 d.No other major complications were observed. CONCLUSION:CT-guided puncture is useful for thetreatment of tumors located in the hepatic dome whichare hardly detectable by US,even though pneumothoraxsometimes may occur as a complication.In the caseswith adhesion in the pleura for which artificial pleuraleffusion methods are not appropriate,CT-guided RFA isthus considered to be an alternative treatment for HCClocated in the hepatic dome.     

Combination of radiofrequency ablation and percutaneous ethanol injection versus radiofrequency ablation alone for hepatocellular carcinoma: a systematic review and meta-analysis

IntroductionRadiofrequency ablation and percutaneous ethanol injection are important treatment modalities for hepatocellular carcinoma patients; Whether a combination treatment yields, additional benefit still remains controversial.MethodsA systematic review and meta-analysis was concluded. Randomized controlled trials published before January 1, 2022, from PubMed, EMBASE, Scopus, and CNKI were searched. Studies were excluded when patients received different ablative treatment or had serious liver dysfunction. The risk of bias assessment was evaluated using the Cochrane Collaboration's tool.ResultsTen studies, encompassing 854 patients, with histologically proven HCC were finally analyzed. The results demonstrated that patients who received RFA-PEI had slightly improvements in 1-year overall survival (OS) [risk ratio (RR): 1.11; 95% confidence interval (CI): 1.03, 1.19, I2 = 10%], 2-year OS (RR: 1.25; 95% CI: 1.12, 1.40, I2 = 0%), 3-year OS (RR: 1.42; 95% CI: 1.11, 1.83, I2 = 38%), 1-year local recurrence-free (LRF) proportion (RR: 1.2; 95% CI: 1.01, 1.42, I2 = 61%), and complete tumor necrosis (CTN) (RR: 1.32; 95% CI: 1.14, 1.53, I2 = 45%). Nevertheless, common complications, such as fever, were found to be significant (RR: 1.78, 95% CI: 1.13, 2.80).ConclusionDespite RFA-PEI appearing to be superior for HCC patients with a compensated liver in terms of OS, current evidence contained moderate to significant heterogeneity, and it was difficult to draw a definite conclusion regarding the therapeutic management in terms of LRF and CTN.     

Postoperative recurrence in hepatocellular carcinoma: Comparison between percutaneous ethanol injection and radiofrequency ablation.

AIM: Recently percutaneous ethanol injection (PEI) turned into percutaneous radiofrequency ablation (PRFA), and it has become widely used for the treatment of hepatocellular carcinoma (HCC). The present study was to compare the incidence in postoperative HCC recurrence between these two therapeutic approaches. METHODS: One hundred and sixty-eight first-time HCC in patient cases were chosen for PEI (n=94) and PRFA (n=74). The localized recurrence rate based on the operator's experience in percutaneous treatment for HCC (on <5 years versus >/=5 years experience) was examined. RESULTS: The PRFA group demonstrated a significantly lower localized recurrence rate within 2 years than the PEI group (8% and 22%, respectively, P<0.01). The local recurrence rate of HCC within 2 years after PEI was significantly lower in those for whom the operator's experience was more than 5 years compared to those for whom it was less than 5 years (12% versus 24%, respectively, P<0.05). In contrast, after PRFA there was no significant difference between these two groups of <5 years and of >/=5 years experience (8% versus 8%, respectively, P=0.98). CONCLUSION: The present study demonstrated that PRFA resulted in a lower rate of local recurrence in comparison to conventional PEI, regardless of the operator's experience.     

Hyperkalaemia after radiofrequency ablation of hepatocellular carcinoma

Radiofrequency ablation of liver tumours is a useful therapy for otherwise unresectable tumours. The complication rate is said to be low. In this case report we describe hyperkalaemia after radiofrequency ablation of a hepatocellular carcinoma in a patient with end-stage renal insufficiency.     

射频消融治疗早期肝癌的荟萃分析

目的 根据现有的临床研究资料评价射频消融(RFA)治疗早期肝癌的疗效与安全性.方法 检索Cochrane图书馆、EMBASE、PubMed、OVID等数据库和中国期刊网中的随机对照试验(RCT)文献,将Jadad评分≥3分的高质量论文纳入研究,并提取纳入研究的特征信息.采用STATA9.0软件进行数据分析,首先进行异质性检验,根据异质性检验结果选择相应的效应模型.然后进行敏感性分析,并以漏斗图和Egger回归方程评定有无发表偏倚.结果 共6篇RCT文献纳入本研究,共包含862例早期肝癌患者.研究表明与其他治疗方法相比,RFA治疗可明显增加早期肝癌患者的3年生存率,并减少了肝内局部复发率,OR值分别为2.06(95%CI为1.54～2.77,P=0.000)和0.40(95%CI为0.28～0.57,P=0.000);而在肝内转移、远处转移、严重副作用等方面差异无统计学意义.漏斗图基本呈现下宽上窄左右对称的图形,Egger线性回归显示3年生存率、肝内局部复发率、肝内转移、远处转移、严重副作用等方面的P值分别为0.670、0.160、0.884、0.087、0.317,提示无发表偏倚.结论 早期肝癌经RFA治疗可获得优于其他疗法的局部疗效和3年生存率.RFA具有微创、简便和经济的优点,有可能作为早期肝癌的首选治疗手段之一.     

Diffuse intrahepatic recurrence after percutaneous radiofrequency ablation for solitary and small hepatocellular carcinoma

Two patients developed segmental, diffuse intrahepatic recurrence after percutaneous radiofrequency ablation (RFA) to treat a primary, solitary, and small (2.5 cm) hepatocellular carcinoma (HCC). Despite the size of the HCC, levels of the tumor markers (α-fetoprotein, α-fetoprotein-L3%, and des-γ-carboxyprothrombin) were all elevated before RFA, and tumors in both patients were contiguous with a major branch of the portal vein. Tumor biopsies of both patients revealed moderately differentiated HCC but diagnostic imaging showed an area of reduced tumor blood flow, suggesting a poorly differentiated component. Since early detection of post-RFA malignancies by standard ultrasonography and contrast-enhanced computed tomography was difficult, the most sensitive indicator of recurrence in these two patients was the elevated tumor markers. The diffuse intrahepatic recurrence was thought to be caused by increased intratumoral pressure during RFA, resulting in the dissemination of cancer cells through the contiguous portal vein. The clinical course of these tumors indicate that the choice of RFA should be carefully considered when treating specific subtype of HCC that is adjacent to main portal vein branch and involves a possible poorly differentiated component and that surgical resection or combinations of RFA with other treatment modalities such as transcatheter arterial chemoembolization should be considered as alternative treatment strategies.     

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.     

Prognostic factors for survival in patients with hepatocellular carcinoma after radiofrequency ablation]

BACKGROUND/AIMS: Currently there is no consensus on which staging system is the best in predicting the survival of patients with hepatocellular carcinoma (HCC). The aim of this study was to identify independent factors to predict survival and to compare 4 available prognostic staging systems in patients with early HCC after radiofrequency ablation. METHODS: We retrospectively studied 100 Korean patients with early HCC. Prognostic factors for survival were analysed by univariate and multivariate analysis using the Kaplan-Meier method and Cox proportional hazard regression models. Okuda, Cancer of the Liver Italian Program (CLIP), TNM and Japanese integrated staging score (JIS score) were evaluated before the treatments. RESULTS: Overall survival rates of 12, 24 and 36 months were 89%, 76%, and 64% respectively and the mean survival duration was 45 months. Multivariable analysis showed that albumin, total bilirubin and size of tumor were independent prognostic factors. Multivariate analysis showed that TNM and JIS score staging systems were significant staging systems for the prediction of prognosis. CONCLUSIONS: Both TNM and JIS score are more effective than the Okuda and CLIP staging systems in stratifying patients into different risk groups with early HCC. However, JIS score gives better prediction of prognosis in patients with HCC after radiofrequency ablation.