Yusuke Okuwaki

Intrahepatic distant recurrence after radiofrequency ablation for a single small hepatocellular carcinoma: risk factors and patterns.

Background. The pathogenesis of frequent intrahepatic recurrence of hepatocellular carcinoma (HCC) after surgical resection or local ablation therapy remains uncertain. Risks and patterns of intrahepatic distant recurrence (IDR) of a single, primary HCC lesion after radiofrequency (RF) ablation were examined. Methods. Ninety patients with a single primary HCC lesion of less than 3 cm who had complete RF ablation were enrolled in the study. Risk factors for IDR and the patterns of IDR after RF ablation were analyzed. Results. The median follow-up was 37.4 months. IDR was observed in 44 (48.9%) patients. The cumulative rate of IDR was 10.4%, 52.5%, and 77.0% at 1, 3, and 5 years, respectively. Univariate analysis revealed that a pretreatment serum α-fetoprotein (AFP) level of ≥50 ng/ml (P = 0.0324), a des-γ-carboxy prothrombin (DCP) level of ≥40 mAu/ml (P = 0.006), an ablative margin of <5 mm of the ablation zone (P = 0.0306), and a prothrombin time of <70% (P = 0.0188) were related to IDR. A multivariate stepwise Cox proportional hazards regression model revealed that pretreatment serum AFP and DCP level and the ablative margin were independent risk factors for IDR pretreatment. Serum DCP level ≥ 40 mAu/ml (P = 0.025), local tumor progression (P = 0.011), and ablative margin < 5 mm (P = 0.024) were related to multiple IDR. Conclusions. HCC patients with high serum AFP or DCP before RF ablation should be carefully followed up to monitor any IDR. A suffi cient ablative margin in RF ablation for HCC is required to prevent IDR.

Early increase in α-fetoprotein for predicting unfavorable clinical outcomes in patients with advanced hepatocellular carcinoma treated with sorafenib.

Background To determine the value of early alterations of the tumor markers &agr;-fetoprotein (AFP) and des-&ggr;-carboxy prothrombin (DCP) for predicting the outcomes of patients with advanced hepatocellular carcinoma (HCC) who receive sorafenib. Materials and methods Tumor response, overall survival (OS), and progression-free survival (PFS) were retrospectively analyzed in 59 patients with advanced HCC. Serum AFP and DCP were examined for early elevation within 4 weeks after the initiation of sorafenib. An increase in AFP was defined as AFP of more than 20%, and an increase in DCP was defined as more than two-fold higher level than the baseline. The relationship of the clinical characteristics, laboratory data at baseline, and early elevations of AFP and DCP with disease progression was analyzed. Results The median OS and PFS were 11 and 3.3 months, respectively. The rate of progressive disease (PD) was 54%, and an early increase in AFP was significantly related to PD (P=0.006) and was a significant independent predictor of both poorer OS and PFS (P<0.001, hazard ratio, 4.14; 95% confidence interval, 1.946–8.811; and P=0.001, hazard ratio, 2.852; 95% confidence interval, 1.524–5.337, respectively). There was no association between early increase in DCP and clinical outcomes. Conclusion Early increase in AFP predicted PD and poorer survival and may thus be a useful biomarker in patients with advanced HCC who receive sorafenib.

Entecavir is an optional agent to prevent hepatitis B virus (HBV) reactivation: A review of 16 patients

BACKGROUND Hepatitis B virus (HBV) reactivation is a fatal complication in patients who receive chemotherapy or immunosuppressive therapy. We examined the effect of preventive entecavir (ETV), a new nucleoside analogue on HBV reactivation during chemotherapy or immunosuppressive therapy. METHODS Between February 2007 and September 2009, sixteen nucleoside analogue treatment-naive patients with chronic HBV infection (HB surface antigen [HBsAg] positive) who required chemotherapy or immunosuppressive therapy were enrolled. Referring to some guidelines, the patients received preventive ETV to reduce incidence of HBV reactivation, and were closely monitored for HBV markers. RESULTS HBV reactivation did not occur in any of the 16 patients and the indispensable treatments for their underlying diseases could be continued. However, HBV relapsed after preventive ETV was discontinued in 2 patients. CONCLUSIONS This study suggests that ETV is a useful option for preventing HBV reactivation in patients with chronic HBV infection.

Repeat Radiofrequency Ablation Provides Survival Benefit in Patients With Intrahepatic Distant Recurrence of Hepatocellular Carcinoma

OBJECTIVES:Intrahepatic distant recurrence (IDR) of hepatocellular carcinoma (HCC) after curative treatment occurs frequently and influences the prognoses. The aim of this study was to determine prognostic factors affecting survival after IDR and the optimum therapy for IDR.METHODS:A total of 115 patients with a single small primary HCC who had complete radiofrequency (RF) ablation were enrolled in this study. The prognostic factors and the optimum therapy affecting survival were statistically analyzed among patients with IDRs.RESULTS:IDRs were observed in 59 (51.3%) patients with the median observation period of 19.6 months. The cumulative rates of IDRs were 11.8, 53.9, and 75.8% at 1, 3, and 5 years, respectively. IDR nodules were present as a single nodule in 38 patients and as multiple nodules in 21 patients. In all, 23 patients died during the follow-up. A total of 30 patients were treated with RF ablation, and 27 were treated with transcatheter arterial chemoembolization (TACE). The overall cumulative survival rates after IDRs were 92.7, 55.4, and 43.7% at 1, 3, and 5 years, respectively. A multivariate analysis showed that treatment with RF ablation for IDR was a significant favorable prognostic factor after IDR (hazard ratio: 0.167, 95% confidence interval: 0.048−0.584, P=0.005). In a comparison of survival after IDR between patients treated with RF ablation and TACE, who were comparable with clinical and tumoral characteristics, the cumulative survival rate of patients treated with RF ablation was significantly higher than that of those treated with TACE (77.2 vs 28.5% at 3 years). The cumulative survival rates obtained from the initial RF ablation of the patients with IDRs treated with repeat RF ablation were similar to those of recurrence-free patients.CONCLUSIONS:Repeat RF ablation should be attempted for IDR as much as possible despite tumor multiplicity for survival benefit; by reducing the need, it will help solve the problem of the current shortage of donors for liver transplantations.

Potential Prognostic Benefits of Radiotherapy as an Initial Treatment for Patients with Unresectable Advanced Hepatocellular Carcinoma with Invasion to Intrahepatic Large Vessels

Objectives: To examine the efficacy and prognostic benefits of radiotherapy (RT) in patients who have unresectable advanced hepatocellular carcinoma (HCC) with invasion to intrahepatic large vessels (IHLVs). Methods: Sixty-eight patients who had advanced HCC with invasion to IHLVs were studied. Thirty-two consecutive patients initially received 3-dimensional conformal RT for HCC invasion to IHLVs. Tumor response, prognostic factors, and survival were studied in the patients given RT. Prognostic factors and survival were assessed in the study group as a whole. Data were analyzed using the Kaplan-Meier method, univariate analysis, and a Cox model. Results: The rate of objective response to RT was 48%. Predictors of survival in the patients who received RT were a hepatic function of Child-Pugh class A (p = 0.0263) and a response to RT (p = 0.0121). In the study group as a whole, independent predictors of survival in a Cox model were multinodular HCC (p = 0.007), inferior vena caval invasion (p = 0.001), a serum α-fetoprotein level of >1,000 ng/ml (p = 0.032), and the performance of RT (p < 0.001). Notably, the median survival of the nonresponders to RT (n = 15) was significantly longer than that of the patients who received no treatment for HCC (n = 21; 7.0 vs. 3.4 months, p = 0.0014). Conclusion: RT is considered an effective initial treatment for HCC invasion to IHLVs, and may offer survival benefits, even in nonresponders, because of the induction of stable disease.

Re-appearance of hepatitis B virus following therapy with rituximab for lymphoma is not rare in Japanese patients with past hepatitis B virus infection.

Background and aim: De novo hepatitis B virus (HBV)‐related hepatitis is a well‐known fatal complication following chemo‐immunosuppressive therapy in patients with past HBV infection (HB surface antigen and serum HBV DNA negative, but HB core antibody and/or HB surface antibody positive). This research was conducted to evaluate the incidence of and clinical features associated with re‐appearance of serum HBV DNA following chemo‐immunosuppressive therapy in Japanese patients with past HBV infection.

Radiotherapy for patients with unresectable advanced hepatocellular carcinoma with invasion to intrahepatic large vessels: Efficacy and outcomes

To examine the efficacy and outcomes of radiotherapy (RT) in patients who have hepatocellular carcinoma with invasion to intrahepatic large vessels (IHLVs).

Therapeutic benefits of partial splenic embolization for thrombocytopenia in hepatocellular carcinoma patients treated with radiofrequency ablation

Aim:  Partial splenic embolization (PSE) is a non‐surgical procedure developed to treat hypersplenism. The purpose of this study is to evaluate therapeutic benefits of PSE with follow‐up radiofrequency ablation (RFA) treatment in hepatocellular carcinoma (HCC) patients with thrombocytopenia.

Field practice study of half-dose sorafenib treatment on safety and efficacy for hepatocellular carcinoma: A propensity score analysis

Patients with hepatocellular carcinoma (HCC) who receive an initial full dose of sorafenib (800 mg/day) often require a decreased dose (400 mg/day) or discontinuation of therapy because of severe adverse events. We conducted a retrospective analysis of patients with HCC to compare the safety and efficacy of full‐ to half‐dose sorafenib.

Reliability and validity of splenic volume measurement by 3‐D ultrasound

Aim:  We prospectively evaluated the reliability and validity of splenic volume with 3‐D ultrasound measurement and clarified its clinical usefulness.