Evaluation of transarterial chemoembolization combined with percutaneous ethanol ablation for large hepatocellular carcinoma

AIM:To assess the effects of combined transcatheter arterial chemoembolization(TACE) and percutaneous ethanol ablation(PEA) in patients with large hepatocellular carcinoma(HCC).METHODS:A total of 63 patients with unresectable large HCC were treated with TACE followed by PEA.The largest dimension of the tumors ranged from 5.3 cm to 17.8 cm.The survival rates,acute effects,toxicity and prognostic factors were analyzed.RESULTS:The cumulative survival rates at 1,3 and 5 years were 59.4%,28.4% and 15.8%,respecti...     

Radiofrequency ablation of hepatocellular carcinoma in patients with cirrhosis

Radiofrequency is an effective therapeutic modality for patients with hepatocellular carcinoma. However few data are available with regard to the complication rate, the feasibility and long term survival. AIMS: To assess the response rate and complications of radiofrequency in cirrhotic patients with hepatocellular carcinoma. PATIENTS AND METHODS: Eighteen patients were enrolled. Each nodule was treated subcutaneously. Treatment response was assessed by computed tomography performed at 24 hours in 10 patients and every 3 months in all patients. Necrosis of the tumor was considered complete when hypodensity without enhanced contrast. RESULTS: Thirty hepatocellular carcinoma nodules with a mean tumor size of 30 mm; 15<30 mm and 15 >=30 mm, were treated by 1.3 radiofrequency sessions. Complete necrosis was achieved in 89%, greater for nodules<30 mm (100%) than for nodules >=30mm (80%). After a median follow up of 10.6 months, survival rate was 50%. Death was related to tumor involvement in 28%, to cirrhosis complications in 17% and to non liver-related disease in 5%. Three major treatment-related complications occurred (10%): subcapsular hematoma, sustained severe pain and peritoneal dissemination. All three complications were related to subcapsular location. CONCLUSION: Radiofrequency may be considered as an alternative treatment to percutaneous ethanol injection for hepatocellular carcinoma; however, subcapsular location has to be excluded when considering the observed morbidity. Prospective studies are warranted to evaluate the efficacy and morbidity of this treatment in hepatocellular carcinoma.     

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.     

Comparison between combination therapy of percutaneous ethanol injection and radiofrequency ablation and radiofrequency ablation alone for patients with hepatocellular carcinoma

ABM: In the present study, the characteristics of PEI-RFA treatment were further elucidated by analyzing the relationship between the volume of coagulated necrosis and the energy requirement for ablation or the amount of ethanol injected into HCC. METHODS: The volume of coagulated necrosis, total energy requirement and energy requirement for coagulation of per unit volume were examined in the groups of PEI-RFA and RFA alone using the Cool-tip RF system. RESULTS: The results showed that the volume of coagulated necrosis induced was significantly larger in PEI-RFA group than in routine RFA group, when the total energy administered was comparable in both groups. In PEI-RFA, enlargement of coagulated necrosis was admitted in 3 dimensions and the amount of energy requirement per unit volume of coagulated necrosis was negatively correlated with the amount of ethanol injected into HCC. CONCLUSION: These results suggest that, compared to RFA alone, PEI-RFA enables to induce comparable coagulated necrosis with smaller energy requirement, and that PEI-RFA is likely to be less invasive than RFA alone irrespective of inducing enhanced coagulated necrosis. Thus, simple prior injection of ethanol may make RFA treatment more effective and less invasive for the treatment of patients with HCC.     

Prognostic factors in patients with small hepatocellular carcinoma treated by percutaneous ethanol injection

BACKGROUND: Percutaneous ethanol injection (PEI) has been widely performed and is now accepted as a viable alternative to hepatic resection in patients with small hepatocellular carcinomas (HCC). However, only a few extensive investigations have been conducted regarding the prognostic factors for HCC patients treated with PEI. METHODS: We investigated the prognostic factors in 100 patients with small HCC who had undergone PEI. Univariate analysis and multivariate analysis with Cox's proportional hazards model were used to determine the factors potentially related to survival. For clinical application, a prognostic index was calculated based on the regression coefficients of the independent variables identified from the multivariate analysis. RESULTS: Median survival time and 1, 3 and 5 year survival rates were 71 months and 100, 84 and 62%, respectively. Among the 15 potential prognostic variables investigated, only three variables, namely a serum albumin level < or = 3.5 g/dL, the presence of tumor stain and a serum glutamic oxaloacetic transaminase level > 66 IU/L, were identified as factors independently associated with a shorter survival. A prognostic index based on the regression coefficients of these three factors was proposed to classify patients into three groups, those with a good (5 year survival rate 91%), intermediate (64%) and poor prognosis (22%). CONCLUSIONS: The results of the present study may be useful in predicting the survival of HCC patients treated with PEI and in the design and analysis of future clinical trials of PEI for HCC.     

Radiofrequency ablation of hepatocellular carcinoma in cirrhotic patients

BACKGROUND/AIMS: Radiofrequency ablation is useful for local destruction of primary and secondary hepatic tumors. However there is little information about long-term outcome for patients with hepatocellular carcinoma and cirrhosis. The aims of this study included the analysis of efficacy in local control of tumors, patterns of recurrence and survival rate related to severity of cirrhosis and tumor features. METHODOLOGY: From January 1998 to January 2001 we ablated 65 hepatocellular carcinomas in 53 patients with cirrhosis. Cirrhosis was related to HCV, HBV and alcohol intake in 32, 4 and 17 patients, respectively. According to Child-Pugh classification 24 and 29 patients belong to A and B class, respectively. Patients in Child-Pugh C class were excluded from the study. The mean diameter of lesions was 4 cm (range: 1-7 cm). In all cases radiofrequency ablation was performed with the percutaneous approach under ultrasound guidance. Treatment efficacy was estimated with dual phase computed tomography and alpha-fetoprotein dosage. RESULTS: Complete necrosis rate after first treatment was 90.9, 74.4 and 36.4% in hepatocellular carcinoma smaller than 3 cm, between 3 and 5 cm and larger than 5 cm, respectively (p = 0.01). After multiple treatment complete necrosis was achieved in 100, 93 and 63.6% (p = 0.01). The mean number of treatments was 1.5 (range: 1-4) per patients. Four lesions of 58 (6.8%) developed local recurrence during a mean follow-up of 18 months. No local recurrence was observed in tumors smaller than 4 cm. New tumors were observed in 15 patients (28.3%). There were no treatment-related deaths and 11 patients (20.7%) suffered minor complications. The survival rate of patients after treatment was 87, 63 and 45% at 12, 24 and 36 months, respectively. Survival was significantly related to Child-Pugh class (p = 0.01). CONCLUSIONS: Radiofrequency ablation is a safe and effective treatment of hepatocellular carcinoma smaller than 5 cm with complete necrosis in most lesions. No local recurrences were observed in lesions smaller than 4 cm. After 3 years survival was 83% in Child-Pugh A cirrhotic patients and 31% in Child-Pugh B patients.     

Radiofrequency ablation improves prognosis compared with ethanol injection for hepatocellular carcinoma < or =4 cm

BACKGROUND & AIMS: The aim of this study was to compare the clinical outcome of percutaneous radiofrequency (RF) ablation, conventional percutaneous ethanol injection (PEI), and higher-dose PEI in treating hepatocellular carcinoma (HCC) 4 cm or less. METHODS: A total of 157 patients with 186 HCCs 4 cm or less were randomly assigned to 3 groups (52 patients in the conventional PEI group, 53 in the higher-dose PEI group, and 52 in the RF group). Clinical outcomes in terms of complete tumor necrosis, overall survival, local tumor progression, additional new tumors, and cancer-free survival were compared across 3 groups. RESULTS: The rate of complete tumor necrosis was 88% in the conventional PEI group, 92% in the higher-dose PEI group, and 96% in the RF group. Significantly fewer sessions were required to achieve complete tumor necrosis in the RF group than in the other 2 groups (P < .01). The local tumor progression rate was lowest in the RF group (vs the conventional PEI group, P = .012; vs the higher-dose PEI group, P = .037). The overall survival rate was highest in the RF group (vs the conventional PEI group, P = .014; vs the higher-dose PEI group, P = .023). The cancer-free survival rate was highest in the RF group (vs the conventional PEI group, P = .019; vs the higher-dose PEI group, P = .024). Multivariate analysis determined that tumor size, tumor differentiation, and the method of treatment (RF vs both methods of PEI) were significant factors in relation to local tumor progression, overall survival, and cancer-free survival. CONCLUSIONS: The results show that RF ablation yielded better clinical outcomes than conventional and higher-dose PEI in treating HCC 4 cm or less.     

Ultrasound guided percutaneous ethanol injection of hepatocellular carcinoma

Percutaneous ethanol injection (PEI), as the first minimally invasive ablation method, has now been in use for more than 20 years. Its main indication is the treatment of small hepatocellular carcinomas superimposed on liver cirrhosis. PEI is highly effective for small tumors (<3 cm) with a complete response in 80% of patients. The efficacy for larger tumors (3-5 cm) is lower, with a complete response in 50%. To increase the effect in larger tumors some special techniques have been developed: single session therapy in general anesthesia, "multiple needles insertion", injection in the feeding artery. PEI is a well tolerated therapy, with a very low complication rate. Recurrences, either local or distant, may occur after PEI and can be treated with new sessions. Although it is still considered the standard percutaneous technique in the treatment of hepatocellular carcinoma, its place is challenged by the new thermal ablative percutaneous techniques, especially radiofrequency ablation.     

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.     

Radiofrequency ablation or percutaneous ethanol injection for the treatment of liver tumors

The liver is a common location of both primary and secondary malignancies. For unresectable liver cancer, many local ablative therapies have been developed. These include e.g., percutaneous ethanol injection (PEI), percutaneous acetic acid injection, radiofrequency ablation (RFA), cryoablation, microwave ablation, laserinduced thermotherapy, and high-intensity focused ultrasound. RFA has recently gained interest and is the most widely applied thermoablative technique. RFA allows more effective tumor control in fewer treatment sessions compared with PEI, but with a higher rate of complications. However, there are certain circumstances where PEI therapy represents a better strategy to control liver tumors than RFA, especially in situations where RFA is difficult, for example when large vessels surround the tumor. In the context of hepatocellular carcinoma (HCC), both RFA and PEI are feasible and of benefit in non-operable patients. RFA seems superior to PEI in HCC 2 cm, and the combination of interventions may be of benefit in selected patients. Liver resection is superior to RFA for patients with HCC meeting the Milan criteria, but RFA can be employed in tumors ≤ 3 cm and where there is an increased expected operative mortality. In addition, some lines of evidence indicate that RFA and PEI can be employed as a bridge to liver transplantation. The use of RFA in colorectal liver metastases is currently limited to unresectable disease and for patients unfit for surgery. The aim of this article is to summarize the current status of RFA in the management of liver tumors and compare it to the cheap and readily available technique of PEI.     

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.     

Combination of repeated single-session percutaneous ethanol injection and transarterial chemoembolisation compared to repeated single-session percutaneous ethanol injection in patients with non-resectable hepatocellular carcinoma

AIM: To evaluate the treatment effect of percutaneous ethanol injection (PEI) for patients with advanced, non-resectable HCC compared with combination of transarterial chemoembolisation (TACE) and repeated single-session PEI, repeated single-session PEI alone, repeated TACE alone, or best supportive care. METHODS: All patients who received PEI treatment during the study period were included and stratified to one of the following treatment modalities according to physical status and tumor extent: combination of TACE and repeated single-session PEI, repeated single-session PEI alone, repeated TACE alone, or best supportive care. Prognostic value of clinical parameters including Okuda-classification, presence of portal vein thrombosis, presence of ascites, number of tumors, maximum tumor diameter, and serum cholinesterase (CHE), as well as Child-Pugh stage, a-fetoprotein (AFP), fever, incidence of complications were assessed and compared between the groups. Survival was determined using Kaplan-Meier and multivariate regression analyses. RESULTS: The 1- and 3-year survival of all patients was 73% and 47%. In the subgroup analyses, the combination of TACE and PEI (1) was associated with a longer survival (1-, 3-, 5-year survival: 90%, 52%, and 43%) compared to PEI treatment alone (2) (1-, 3-, 5-year survival: 65%, 50%, and 37%). Secondary PEI after initial stratification to TACE (3) yielded comparable results (1-, 3-, 5-year survival: 91%, 40%, and 30%) while PEI after stratification to best supportive care (4) was associated with decreased survival (1-, 3-, 5-year survival: 50%, 23%, 12%). Apart from the chosen treatment modalities, predictors for better survival were tumor number (n < 5), tumor size (< 5 cm), no ascites before PEI, and stable serum cholinesterase after PEI (P < 0.05). The mortality within 2 wk after PEI was 2.8% (n = 3). There were 24 (8.9%) major complications after PEI including segmental liver infarction, focal liver necrosis, and liver abscess. All complications could be managed non-surgically. CONCLUSION: Repeated single-session PEI is effective in patients with advanced HCC at an acceptable and manageable complication rate. Patients stratified to a combination of TACE and PEI can expect longer survival than those stratified to repeated PEI alone. Furthermore, patients with large or multiple tumors in good clinical status may also profit from a combination of TACE and reconsideration for secondary PEI.     

Ultrasonically guided percutaneous ethanol injection therapy for hepatocellular carcinoma

Ultrasonically guided percutaneous ethanol injection therapy (US-PEIT) was performed in 26 patients with hepatocellular carcinomas (HCC) in whom neither surgery nor transcatheter arterial embolization (TAE) was indicated, or TAE had proved ineffective. Comparison of results by various diagnostic imaging techniques with histopathological findings revealed that tumor necrosis after US-PEIT was correlated with increased echogenicity of the tumor by US, decreased density of the tumor and disappearance of contrast enhancement by computed tomography (CT), and change to a lower signal in the tumor by magnetic resonance imaging [MRI, 0.15 T permanent magnet, spin-echo sequence, repetition time (TR)/echo time (TE) = 2000/80 ms]. Thus, findings by imaging are useful in evaluating the initial effect of US-PEIT. Of three specimens obtained by liver resection and three obtained at autopsy, four showed complete necrosis after US-PEIT (maximum tumor diameter, 3 cm). This method also appeared to be effective in cases of capsular invasion. In this study, the 2-yr survival rate of patients with HCC was 75%. Although this study was not a controlled clinical trial, we conclude that US-PEIT may be a potentially effective treatment for HCC.     

射频消融与无水酒精注射治疗术后复发肝细胞癌患者的疗效比较

目的对比肝细胞癌（HCC）术后复发肿瘤病灶经射频消融（RFA）与无水酒精（PEI）注射治疗的疗效,以期为临床治疗HCC肿瘤复发提供参考。方法回顾性分析2007年8月至2010年1月HCC术后单一病灶复发患者175例,分为PEI治疗101例与RFA治疗74例。所有病例治疗前后均行常规彩超和超声造影/增强CT检查,观察比较治疗次数、病灶完全灭活率及治疗并发症发生率,记录患者治疗后1、2、3年生存率。计量资料采用t检验,计数资料采用χ2检验。结果 HCC术后复发病灶,平均每例的PEI治疗次数多于RFA（P〈0.05）,PEI和RFA治疗并发症的发生率比较差异无统计学意义（P〉0.05）;肿瘤直径〈2.0 cm的HCC术后复发病灶组中,PEI和RFA治疗病灶完全灭活率比较差异无统计学意义（P〉0.05）,而2.0～5.0 cm HCC术后复发病灶组,PEI治疗病灶完全灭活率低于RFA,差异均有统计学意义（P〈0.05）。HCC术后复发病灶直径〈2.0 cm组中,PEI和RFA治疗术后1、2、3年生存率分别为89.1%和90.2%、69.1%和70.7%、49.1%和53.7%,两种治疗方式术后生存率比较差异无统计学意义（P〉0.05）。而2.0～5.0cm组中,PEI和RFA治疗术后1、2、3年生存率分别为63.0%和84.8%、43.5%和66.7%、21.7%和45.5%,两种治疗方式术后生存率比较差异均有统计学意义（P〈0.05）。结论肿瘤直径小于2.0 cm HCC术后复发病灶的RFA和PEI局部消融治疗,患者术后的生存率无明显差异,而肿瘤直径2.0～5.0 cm时,RFA治疗后生存期优于PEI。     

经皮冷消融联合酒精注射治疗不能切除的肝细胞癌

目的：评价经皮冷消融联合经皮酒精注射(PEI)治疗不能切除的肝细胞癌(HCC)的有效性和安全性。方法：65例HCC患者共105个肿瘤块接受经皮冷消融治疗。冷消融采用cRYOCARE系统，氩气作为冷却剂，共给予2次冷却-复温循环，每次冷却时冷冻刀顶端温度为-180℃。其中36例瘤块直径大于6cm的患者，在冷消融治疗后1～2周接受PEI治疗，每周1次，连续4～6次。结果：在平均随访期为16个月(5～21个月)内，32例(49．2％)无瘤生存，22例(33．8％)生存但有肿瘤复发，其中2例骨转移，3例肺转移，其余17例为肝内复发，但仅有3例是原先冷消融部位复发。在随访1年以上的41例患者中，有32例(78％)迄今仍生存，包括无复发和有复发的病例。8例(12．3％)死于肿瘤复发，3例(4．6％)死于非癌性原因。有CT复查资料的43例中，38例(88．4％)显示肿瘤缩小。冷消融治疗后22例行瘤块活检，除1例外，均显示为坏死性疤痕组织。冷消融治疗前血清甲胎蛋白(AFP)升高的病例中，91．3％在治疗后3～6个月内AFP下降至正常或接近正常。冷消融并发症包括1例发生肝包膜开裂，4例发生一过性血小板降低，2例发生无症状性右侧胸腔积液，2例在原先冷消融部位发生肝脓肿。结论：经皮冷消融为不能手术切除的HCC提供了安全而有效的治疗手段。     

单纯肝动脉栓塞化疗或联合无水酒精注射治疗肝细胞癌疗效比较的Meta分析

目的评价肝动脉栓塞化疗（TACE）联合无水乙醇注射治疗肝细胞癌的疗效和安全性。方法检索PubMed、Cochrane图书馆、Embase、中国生物医学数据库和万方数据库至2012年12月的最新数据,收集所有TACE联合无水乙醇注射与单纯TACE治疗肝细胞癌患者的随机对照研究（RCT）。按照纳入和排除标准选择文献、提取资料和评价纳入研究的方法学质量后,采用RevMan 5.1进行Meta分析。结果在13个RCT共962例患者,显示TACE联合无水乙醇注射治疗1年、2年和3年生存率均较单纯TACE更优,其OR值分别为3.78（95%CI为2.79-5.12）、3.07（95%CI为2.27-4.17）和5.84（95%CI为2.86-11.93）;在其中6个RCT共294例患者,联合治疗患者血清甲胎蛋白下降至正常者显著优于单纯TACE治疗组（OR=4.0,95%CI为2.24-7.15）,但两组间AFP下降（≥25%）而未达正常者无明显差异（OR=1.24,95%CI为0.68-2.27）;两组均未出现严重的不良反应。结论 TACE联合无水乙醇注射治疗患者生存率及AFP下降至正常均优于单纯TACE治疗,患者的生存率明显提高,无严重的不良反应。     

Radiofrequency thermal ablation of hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is one of the major malignancies worldwide. Due to advanced or decompensated liver cirrhosis, comorbidity and multicentricity of the tumor lesions, 70-80% of HCC patients are inoperable at the time of diagnosis. Radiofrequency thermal ablation (RFTA) is a new minimally invasive and sage technique for the nonsurgical treatment of HCCs. Similar to other ablation techniques, the treatment strategy depends on several factors, including the patient's clinical status, the stage of liver cirrhosis and of the HCC. RFTA can be performed percutaneously, laparoscopically or after laparotomy. Advanced RFTA equipment, refined techniques of modifying tumor tissue response to RFTA, and combined treatment strategies should lead to better response rates even in larger HCCs.