Risk factors for the local recurrence of hepatocellular carcinoma after a single session of percutaneous radiofrequency ablation

Background Radiofrequency ablation (RFA) is a new, minimally invasive treatment for hepatocellular carcinoma (HCC). However, there is little available information regarding local recurrence after a single session of RFA with a single electrode insertion.Methods From February 1999 to September 2001, we treated 104 HCC tumors with an expandable needle with four hooks. Ninety-nine of the 104 tumors were successfully treated by single-session RFA with a single electrode insertion. We investigated the relationships between pretreatment factors (tumor size, tumor staining, tumor capsule, and tumor location) and local recurrence in these 99 tumors.Results The mean size of the 99 tumors was 21.5mm in diameter (range, 10 to 33mm). The overall local recurrence rates were 9.7%, 15.4%, and 20.4%, at 1, 2, and 3 years, respectively. For small tumors (smaller than 25mm), the local recurrence rates at 1, 2, and 3 years were 4.0%, 8.0%, and 14.6%, respectively. The local recurrence rates were 21.1% and 32.3% at 1 and 2 years, respectively, for large tumors (25mm or larger), and at 3 years the rate was over 50% for tumors located close to the liver surface. Tumor size and tumor location relative to the liver surface were significantly associated with a higher local recurrence rate. However, other variables tested showed no significant relationship to the local recurrence rate.Conclusions This study demonstrated that both tumor size and location relative to the liver surface influence the local efficacy of single-session RFA with a single electrode insertion.     

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.     

Risk factors for local and distant recurrence of hepatocellular carcinomas after local ablation therapies

Background and Aim: Hepatocellular carcinoma (HCC) recurs frequently after local ablation therapies. Recurrence following the therapies may be of two types: local recurrence and distant recurrence. The aim of the current study is to separately elucidate the predisposing factors for each recurrence. Methods: Among the 2141 consecutive patients with HCC who were admitted to our institute and affiliated hospital between May 1997 and April 2004, 621 patients who had undergone local ablation therapies as the initial treatment were enrolled. Correlations between the clinical backgrounds of the patients and the type of recurrence were analyzed by the Cox proportional hazard model. Results: A multivariate analysis revealed that tumor size (>30 mm; risk ratio 2.80; 95% confidence interval, 1.77–4.45; P < 0.0001), tumor number (≥2; 1.74, 1.23–2.47, P = 0.002), and the serum α‐fetoprotein level (>100 ng/mL; (1.62, 1.09–2.41, P = 0.014), which were classified as “tumor factors”, were significant predisposing factors for the local recurrence of HCC. In contrast, a low platelet count (<100 000/μL; 1.34, 1.04–1.74, P = 0.03) and the presence of ascites (1.73, 1.16–2.57, P = 0.008), which were classified as “background factors”, as well as tumor size (1.83, 1.11–3.01, P = 0.02) and tumor number (2.23, 1.72–3.00, P < 0.0001) were predisposing factors for distant recurrence. Conclusion: The predisposing factors for local and distant recurrence of HCC differ and different precautions must be observed to prevent recurrence, depending on the HCC status and background liver functions.     

Risk factors for early recurrence of small hepatocellular carcinoma after curative resection

BACKGROUND:Poorer prognosis is seen in patients with hepatocellular carcinoma (HCC) after curative hepatic resection with early recurrence (≤1 year) than in those with late recurrence (>1 year).This study aimed to identify risk factors for postoperative early recurrence of small HCC (≤3 cm in diameter).METHODS:The study population consisted of 158 patients who underwent curative resection for small HCC between January 2002 and July 2004.Risk factors for early recurrence were analyzed.RESULTS:Thirty-three (2...     

Intrahepatic bile duct dilatation after percutaneous radiofrequency ablation for hepatocellular carcinoma: impact on patient's prognosis

Background: Percutaneous radiofrequency ablation (RFA) has been widely accepted as an alternative to surgery for small hepatocellular carcinoma (HCC). In RFA, a portion of liver tissue surrounding tumour is also ablated to achieve a safety margin. The intrahepatic bile duct may be injured and result in chronic bile duct dilatation upstream of the injured site. However, the impact of such an injury on the overall prognosis has been unclear. Methods: Patients who showed bile duct dilatation following RFA were identified by a retrospective review of imaging studies. Each dilatation was classified as mild (limited to one hepatic subsegment) or severe (affecting two or more subsegments). The relation between the incidence of intrahepatic bile duct dilatation and HCC recurrence or survival was analysed using proportional hazard models. Results: Among 589 consecutive HCC patients treated with RFA, 70 (11.9%) and 21 (3.6%) patients showed mild and severe bile duct dilatation respectively. Patients with severe dilatation, but not those with mild dilatation, had lower survival and higher HCC recurrence than patients without dilatation. Severe dilatation, but not mild dilatation, was significantly associated with death [hazard ratio (HR) 2.17, P=0.035] and recurrence (HR 2.89, P<0.001). Conclusion: Whereas mild bile duct dilatation after RFA is clinically negligible, bile duct dilatation affecting two or more subsegments should be regarded as a complication that may affect the prognosis and should be observed carefully.     

Intrahepatic dissemination of hepatocellular carcinoma after local ablation therapy

Background/Purpose

We aimed to clarify the histological features of and risk factors for intrahepatic dissemination after local ablation therapy (LAT) for hepatocellular carcinoma (HCC).

Methods

Between April 1992 and December 2005, 192 HCC patients underwent hepatic resection at our department, among whom were 17 patients who had local recurrences after LAT. Eight of these 17 patients had intrahepatic dissemination. The clinical and histological characteristics of these 8 surgically treated patients with intrahepatic dissemination were investigated.

Results

Histologically, numerous intrahepatic metastases were observed, mainly in the same section as the treated tumor, together with main or sectional portal vein tumor thrombi. Before the ablation therapy, the average tumor diameter was 2.1 cm, and 62.5% of the tumors were adjacent to the main or sectional portal vein. In terms of therapeutic factors, 25% of the patients had a prior needle biopsy and 62.5% had insufficient safety margins.

Conclusions

LAT for HCCs (even those less than 3 cm in diameter) adjacent less than 5 mm to the main or sectional portal vein possibly promotes intrahepatic dissemination.     

肝细胞肝癌射频术后肝内复发情况及其影响因素分析

目的探讨肝细胞肝癌射频灭活后肝内复发情况及其影响因素。方法2001年3月至2006年8月共47例患者55个肿瘤接受射频治疗。患者肝功能Child—Pugh分级为A或B级，肿瘤直径小于5cm，病灶数目不超过3个。随访肿瘤多发情况，时间6～71个月，射频后的肝内复发分为肿瘤局部复发与肝内远处转移。分析因素包括患者全身情况（有无肝炎肝硬化、肝功能Chilcl-Pugh分级、血清甲胎蛋白水平）、肿瘤局部情况（大小、位置、数目）与治疗方法。采用Kaplan-Meier模型计算无瘤生存期，Log—rank检验进行单因素分析，Cox比例风险模型进行多因素分析。结果全组共25例患者出现肝内复发，其中8例肿瘤局部复发，14例肝内远处转移，3例同时合并局部及远处转移。射频术后1、2、3年肝内累计无瘤生存率分别为57．3％、40，3％、35．3％。单因素Log—rank检验显示肝内复发与肿瘤大小、位置与肝功能Child-Pugh分级相关。Cox比例风险模型显示肿瘤大小和肝功能Child—Pugh分级是影响肿瘤局部复发的危险因素，肿瘤数目是影响肝内远处转移的危险因素。结论选择肝功能Child-PughA级，直径≤3cm的单发肿瘤患者进行射频治疗，有助于提高疗效，降低术后肝内复发的风险。     

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.     

Repeated radiofrequency ablation for the distant recurrence in the liver in patients with chronic hepatitis C virus infection achieving long-term survival

Recurrence of hepatocellular carcinoma (HCC) is frequently observed in patients with hepatitis C virus (HCV) infection and the incidence of HCC recurrence is as high as 20% in these patients even after a complete curative treatment is given for the HCC nodules. We report a 57-year-old female who was referred to our hospital for the treatment of a HCC nodule of 1.8 cm diameter in S5 and having liver cirrhosis of Child–Pugh A classification with HCV infection in April 1999. The HCC nodule showed hypervascularity by computed tomography during hepatic arteriography (CTHA) and was coagulated by microwave under peritoneoscopy. Complete necrosis was confirmed by enhanced-CT scan after microwave coagulation. Thereafter, interferon alfa-2b (3MU, twice weekly) was given but HCV RNA continued to be positive. Thereafter, recurrence of HCC was noted five times in S1, S2, S6; treatment by radiofrequency ablation was given four times; and transarterial chemoembolization was carried out once. Since January 2004, peg-interferon alfa-2a (90 µm/week) has been administered, and no recurrence has been detected until August 2005. She is currently 63 years old, and quite well. Five-year-survival rate in HCC patients treated by radiofrequency ablation is 62.7% in our hospital, however, the recurrence rate is as high as 26.4% per year in the patients with chronic HCV infection. It is a point of controversy when liver transplantation should be recommended in HCC patients with liver cirrhosis of Child-Pugh A classification having chronic HCV infection because of the high incidence of recurrence.     

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.     

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.     

Combination therapy of radiofrequency ablation and transarterial chemoembolization in recurrent hepatocellular carcinoma after hepatectomy compared with single treatment

Aim:  To assess the efficacy and safety of radiofrequency ablation (RFA) combined with transarterial chemoembolization (TACE) in recurrent hepatocellular carcinoma (HCC) after hepatectomy and to compare its outcome with a single modality.
Method:  We retrospectively studied 103 patients with recurrent HCCs after hepatectomy who were excluded from repeat hepatectomy. Of them, 81 patients were male and 22 were female (mean age 55.8 ± 10.7 years; range, 30–80 years). According to treatment modality, these patients were divided into three groups: RFA was used as the sole first-line anticancer treatment in 37 patients (RFA group); TACE was used as the sole first-line anticancer treatment in 35 patients (TACE group). RFA followed by TACE was performed in 31 patients (combination group). There was no significant difference in clinical material between the three groups. Indices including treatment success rate, intrahepatic recurrence rate and survival were obtained for analysis and comparison.
Results:  The treatment success rate of the combination group was significantly higher than that of the TACE group (93.5 vs. 68.6%, P  = 0.011). The intrahepatic recurrence rate of the combination group was significantly lower than that of the TACE group (20.7 vs 57.1%, P  = 0.002) and the RFA group (20.7 vs 43.2%, P  = 0.036). The overall 1-, 3- and 5-year survival rates were 73.9, 51.1 and 28.0% respectively in the RFA group; 65.8, 38.9 and 19.5% respectively in the TACE group; and 88.5, 64.6 and 44.3% respectively in the combination group. There was a significant difference in survival between the combination group and the TACE group ( P  = 0.028).
Conclusion:  RFA combined with TACE was more effective in treating recurrent HCC after hepatectomy compared to single RFA or TACE treatment. This combination therapy can thus be a valuable choice of treatment for recurrent HCC.