Neutrophil-to-lymphocyte ratio associated with mortality in early hepatocellular carcinoma patients after radiofrequency ablation

Background and Aim: Increasing evidence correlates the presence of systemic inflammation with poor survival in patients with hepatocellular carcinoma (HCC). We studied whether peripheral blood neutrophil‐to‐lymphocyte ratio (NLR), a marker of systemic inflammatory response, would be a useful predictor for outcome in patients with early HCC undergoing radiofrequency ablation (RFA). Methods: A total of 158 patients with early HCC underwent RFA. Potential prognostic factors such as age, gender, tumoral characteristics, Child‐Turcotte‐Pugh (CTP) class and NLR were analyzed. The study endpoints were overall survival (OS) and new recurrence. Results: We modeled NLR as a continuous explanatory variable in regression analyses. Multivariate analysis revealed that tumor size (P = 0.005) and high baseline NLR (P = 0.001) were independent explanatory variables associated with unfavorable OS. Regarding new recurrence, multivariate analysis showed that CTP class B (P = 0.002), α‐fetoprotein > 400 ng/mL (P = 0.030), tumor size (P = 0.002) and tumor multiplicity (P = 0.013) were found to be worse prognosticators, but not baseline NLR. In a subset analysis of 140 patients whose post‐RFA NLR data at first follow‐up visit were available, multivariate analysis revealed that high post‐RFA NLR was identified as an independent covariate, not only for OS (P = 0.006), but for new recurrence (P = 0.010) as well. Conclusions: High baseline NLR was associated with worse OS for patients with early HCC; post‐RFA NLR predicted not only OS, but also tumor recurrence.     

Metformin and reduced risk of hepatocellular carcinoma in diabetic patients with chronic liver disease

Background: Previous studies have reported the association between type 2 diabetes mellitus (DM2) and hepatocellular carcinoma (HCC). Aims: To explore the relationships among DM2, antidiabetic therapy and HCC risk. Methods: We recruited 610 HCC patients compared with 618 matched cirrhotic patients and 1696 Controls. The odds ratio (OR) for HCC in diabetic subjects treated with insulin, sulphonylureas and metformin was calculated. Results: DM2 prevalence was 31.2% in HCC, 23.3% in cirrhotic patients and 12.7% in Controls (P<0.0001). The OR for HCC in diabetic HCC patients vs Controls was 3.12 [confidence interval (CI) 2.40–3.90; P<0.001] in univariate analysis and 2.50 (CI 1.70–3.69; P<0.0001) in multivariate analysis. Comparing diabetic HCC patients vs liver cirrhosis (LC) cases, univariate analysis showed an OR for HCC of 2.09 (CI 1.50–2.90; P<0.001), whereas on multivariate analysis we found an OR of 1.46 (CI 1.07–1.98; P=0.02). In 84% of the cases, type 2 diabetes mellitus has been present before the HCC diagnosis. Multivariate analysis showed that metformin treatment was associated with a strong and statistically significant reduction of the risk of HCC, as compared with the use of sulphonylureas or insulin, in diabetic HCC patients vs Controls and vs LC cases (OR of 0.15; CI 0.04–0.50; P=0.005 and OR=0.16; CI 0.06–0.46; P=0.0006 respectively). Conclusions: Our study shows that DM2 is an independent risk factor for HCC and pre‐exists to HCC occurrence. In DM2 patients with HCC, metformin therapy is associated with a reduced HCC risk and seems to have a protective effect on HCC development.     

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.     

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.     

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.     

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 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.     

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.     

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.     

Usefulness of the hyperechoic rim for assessing the therapeutic efficacy of radiofrequency ablation in hepatocellular carcinoma patients

Aim:  During radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC), a hyperechoic rim develops around the HCC nodules. The usefulness of the hyperechoic rim to guide treatment was assessed.
Methods:  RFA was first performed in pig livers to determine the significance of the hyperechoic rim. Fifty-five patients with 75 HCC nodules had received RFA for the treatment of HCC. For those patients, we evaluated whether conventional ultrasonography (US) could be used instead of contrast-enhanced computed tomography (CECT) and contrast-enhanced ultrasonography (CEUS) using virtual imaging. Finally, 31 patients with 45 HCC nodules received RFA, and the degree of ablation was assessed based on the hyperechoic rim. Repeated RFA was done when ablation appeared incomplete.
Results:  In the pig livers, the hyperechoic rim was found to be related to the presence of dead cells. The preliminary study showed that US could be used instead of CECT and CEUS to evaluate the degree of ablation caused by RFA. Because hepatic vessels in the back side of the hyperechoic rim were not clear by the artifact, we used the distance from the surface of the liver to the hyperechoic rim for evaluation. By analyzing the extent of the hyperechoic rim, it was noted that incomplete ablation was achieved in 17 of 31 patients (21 of 45 HCC nodules). These patients were re-treated with RFA within 5–15 min of the first RFA.
Conclusion:  This study shows that the hyperechoic rim is related to the presence of dead and necrotic tissues. Thus, assessment of the hyperechoic rim's characteristics allows one to evaluate the efficacy of RFA.     

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.     

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.     

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.     

External beam radiotherapy to treat intra- and extra-hepatic dissemination of hepatocellular carcinoma after radiofrequency thermal ablation

BACKGROUND: Radiofrequency ablation (RFA) is an alternative to percutaneous ethanol injection therapy (PEIT) for single non-surgical hepatocellular carcinoma. However, the risk of seeding along the needle track has been reported. METHODS: Seven patients presenting with neoplastic seeding after RFA or PEIT were treated with external beam radiotherapy using conventional fractionation. All patients underwent irradiation with a total dose in the range of 44-61 Gy (median and mode value: 50 Gy). RESULTS: An objective response to treatment was achieved in six of seven patients (86%). A complete response was obtained in two patients (29%). The median survival time was 14.7 months and the actuarial 1- and 2-year survivals were 67% and 50%, respectively. CONCLUSIONS: The response to treatment was relatively good without serious complications. Seeding from hepatocellular carcinoma is sensitive to external beam radiotherapy. It is useful in the treatment of these patients with 50 Gy in 25 fractions.