Chikara Ogawa

Percutaneous ultrasound-guided radiofrequency ablation with artificial pleural effusion for hepatocellular carcinoma in the hepatic dome

BackgroundNodules of hepatocellular carcinoma (HCC) located in the hepatic dome cannot be depicted on ultrasography because of pulmonary air. Therefore, percutaneous treatment is not possible in such cases. The purpose of this study was to clarify the feasibility and safety of percutaneous sonographically guided radiofrequency (RF) ablation with the concurrent use of artificial pleural effusion for HCC located in the right subphrenic region.MethodsBetween May 2001 and June 2002, 24 patients with 28 HCC nodules located directly below the diaphragm were enrolled in this study. The patient population included 17 men and 7 women (age range, 51–87 years; mean age, 66.5 years). The maximum diameter of the HCC nodules ranged from 1.0 cm to 4 cm (mean ± SD, 2.1 ± 0.8 cm).ResultsWe infused 200–1100 ml of 5% glucose solution intrathoracically to separate the lung and liver; thus, obtaining an image of the whole tumor was impossible on gray-scale sonography. Complete tumor necrosis was achieved in a single session of RF ablation in 27 (96.4%) of the 28 lesions, while two sessions of RF ablation were required for the remaining lesion (3.6%). During treatment, no dyspnea or other complications concerned with the respiratory system were observed. Clinical courses have been satisfactory without recurrences at 1–13 months after treatment (mean, 7.9 months).ConclusionsPercutaneous RF ablation with artificial pleural effusion in patients with HCC in the hepatic dome may be a safe and feasible therapy.

Efficacy of probiotic treatment with Bifidobacterium longum 536 for induction of remission in active ulcerative colitis: A randomized, double‐blinded, placebo‐controlled multicenter trial

We conducted a randomized, double‐blinded, placebo‐controlled trial to investigate the efficacy of Bifidobacterium longum 536 (BB536) supplementation for induction of remission in Japanese patients with active ulcerative colitis (UC).

Clinical features associated with radiological response to sorafenib in unresectable hepatocellular carcinoma: a large multicenter study in Japan

There have been no established predictive factors of responders to sorafenib in patients with unresectable hepatocellular carcinoma (HCC). This study aimed to investigate the factors predicting a good response to sorafenib in Japanese patients with HCC.

Sorafenib Therapy for BCLC Stage B/C Hepatocellular Carcinoma; Clinical Outcome and Safety in Aged Patients: A Multicenter Study in Japan

Background and aims: We aimed to compare clinical outcomes and safety after sorafenib therapy between patients with Barcelona Clinic Liver Cancer (BCLC) stage B or C hepatocellular carcinoma (HCC) aged ≥75 years (aged group, n=179) and those with BCLC stage B or C HCC aged <75 years (control group, n=279). Patients and methods: We compared overall survival (OS), progression free survival (PFS), best treatment response and sorafenib related serious adverse events (SAEs) of grade 3 or more in the two groups. Furthermore, for reducing the selection bias, we compared clinical outcome of these two groups using propensity score matching analysis. Results: The median OS and PFS intervals were 9.7 and 3.8 months in the aged group and 8.2 and 3.3 months in the control group (P=0.641 for OS and P=0.068 for PFS). Disease control rates were 49.2% (88/179) in the aged group and 49.1% (137/279) in the control group (P>0.999). Objective response rates were 15.1% (27/179) in the aged group and 14.3% (40/279) in the control group (P=0.892). Treatment related SAEs of grade 3 or more were observed in 51 patients (28.5%) in the aged group and in 69 patients (24.7%) in the control group (P=0.385). In the propensity score matched cohort (132 pairs), no significant difference in the two groups was observed in terms of OS (P=0.898) and PFS (P=0.407). Conclusion: In BCLC stage B or C HCC patients treated with sorafenib, life expectancy, disease progression, treatment efficacy and SAEs are unaffected by age over 75 years.

Comparison of standard-dose and half‑dose sorafenib therapy on clinical outcome in patients with unresectable hepatocellular carcinoma in field practice: A propensity score matching analysis

The aims of the present study were to examine whether unresectable hepatocellular carcinoma (HCC) patients treated with initial dose of sorafenib of 400 mg/day (half-dose group) had comparable treatment efficacy, safety and survival merit as compared with those treated with initial dose of sorafenib of 800 mg/day (standard-dose group) in a multicenter large study. For reducing the bias in patient selection, we compared clinical outcomes of these two groups using propensity score matching analysis. A total of 465 patients were treated with sorafenib at fourteen hospitals in Japanese Red Cross Liver Study Group from 2008 to 2013. After propensity score matching, 139 matched HCC patients were selected for analysis in both groups. We retrospectively compared overall survival (OS), progression-free survival (PFS), best treatment response and sorafenib related serious adverse events (SAEs) in the two groups. There were no relevant differences in terms of OS (median OS intervals: 9.2 months in the standard-dose group and 9.7 months in the half‑dose group, P=0.350), PFS (median PFS intervals: 3.4 months in the standard-dose group and 3.2 months in the half-dose group, P=0.729) and best treatment efficacy (objective response rate: P=0.416; disease control rate: P=0.719). Grade 3 or more SAEs were observed in 37 patients (26.6%) in the standard-dose group and 33 patients (23.7%) in the half-dose group (P=0.580). Furthermore, in all subgroup analyses according to Child-Pugh classification and Barcelona Clinic Liver Cancer stage, there were no significant differences in the two groups. In conclusion, unresectable HCC patients treated with initial half‑dose sorafenib had comparable prognosis compared with those treated with initial standard-dose sorafenib.

Hepatocellular carcinoma mimicking cavernous hemangioma on angiography and contrast enhanced harmonic ultrasonography. A case report

A 73-year-old man with chronic hepatitis due to hepatitis C virus was referred to our hospital for close examination of hepatic nodule. An abdominal ultrasonography revealed a mosaic pattern nodule with 3.7 cm in diameter. Arterial phase of dynamic CT revealed the small caudal part and marginal area of cranial part of the tumor were enhanced. The enhancement of marginal area of cranial part of the tumor continued up to portal phase and equilibrium phase and enhanced area was gradually filling in to the central area. On the other hand, the caudal part of the tumor was less enhanced compared with surrounding normal hepatic area in portal phase and equilibrium phase. An abdominal angiography revealed spotty tumor staining mimicking cotton-wool appearance, which is a typical finding for cavernous hemangioma. Contrast enhanced harmonic ultrasonography also showed hemangioma like finding (peripheral globular enhancing pattern). Because of these discrepancies on imagings, it was difficult to make final diagnosis of this tumor to be hepatocellular carcinoma since cavernous hemangioma cannot be completely ruled out. The pathological study of the specimen taken by US-guided percutaneous needle biopsy finally confirmed this nodule as hepatocellular carcinoma. In conclusion, we must keep in mind that some hepatocellular carcinomas could mimic hemangioma due to peliotic change or large acinar formation, therefore, needle liver biopsy may be essential for correct diagnosis if there is a discrepancy in several imaging findings.

Does interferon-free direct-acting antiviral therapy for hepatitis C after curative treatment for hepatocellular carcinoma lead to unexpected recurrences of HCC? A multicenter study by the Japanese Red Cross Hospital Liver Study Group

Background and aim This study aimed to elucidate whether interferon (IFN)-free direct-acting antiviral (DAA) therapy for hepatitis C after curative treatment of hepatocellular carcinoma (HCC) promotes HCC recurrence in a real-world large-scale cohort. Methods This multicenter study was conducted by the Japanese Red Cross Hospital Liver Study Group. This retrospective study analyzed 516 patients who underwent antiviral treatment for hepatitis C with either IFN (n = 148) or IFN-free DAA (n = 368) after curative HCC treatment; 78 IFN-treated patients and 347 IFN-free DAA-treated patients achieved sustained virological response (SVR). The recurrence rate of HCC was compared between the antiviral therapies. Logistic analysis and Cox proportional hazards analysis identified factors associated with early recurrence of HCC within 24 weeks of antiviral therapy and recurrence throughout the observation period, respectively. Results AFP at the completion of antiviral therapy, clinical stage of HCC, and non-SVR were independent factors associated with early recurrence of HCC. Among patients who had achieved SVR, the clinical stage of HCC and the level of AFP at completion of antiviral therapy were independent factors associated with early recurrence of HCC. For recurrence throughout the observation period in SVR patients, AFP at completion of antiviral therapy, duration between last HCC treatment to antiviral therapy, and the number of treatments were independent factors. There was no significant difference in the rate of early recurrence of HCC or recurrence throughout the observation period between IFN and IFN-free DAA treated patients. Conclusions There were no differences in the early recurrence rate of HCC between patients who underwent IFN and those who underwent IFN-free DAA as antiviral therapies.

Hand-Foot Syndrome and Post-Progression Treatment Are the Good Predictors of Better Survival in Advanced Hepatocellular Carcinoma Treated with Sorafenib: A Multicenter Study

Objective: To determine the relationship between treatment outcomes and hand-foot syndrome (HFS), and the relationship between survival rate and post-progression treatment after sorafenib therapy. Methods: The study assessed 314 patients with advanced hepatocellular carcinoma (HCC) treated with sorafenib at 5 general hospitals in Kagawa Prefecture, Japan. Results: At the start of sorafenib therapy, 23.6% of the patients had HCC of a Child-Pugh class other than A. The initial sorafenib dose was 800 mg in 9.2% of the patients and 400 mg in 64.3%. Time to progression was 129 days (95% CI: 87.3-170.7) and the median overall survival (OS) was 392 days (95% CI: 316.0-468.0). The OS of the patients with Child-Pugh class A HCC was significantly better than that of the patients with Child-Pugh class B HCC (p < 0.0001). The survival curves for Child-Pugh class A-5 points and class A-6 points were significantly different, with that for class A-5 points being better (p < 0.0001). A significant difference was observed between the patients who exhibited HFS and those who did not, with the former exhibiting a better survival rate (p < 0.001). In addition, the survival rate of the patients who received post-progression treatment after sorafenib therapy was significantly better than that of the patients who did not (p < 0.001). Conclusion: In sorafenib therapy, patients with HFS and those who received post-progression treatment exhibited good OS.

Proposal of Japan Red Cross score for sorafenib therapy in hepatocellular carcinoma

There have been no established predictors of the outcome on sorafenib therapy for hepatocellular carcinoma (HCC) patients. We aimed to establish a new prognostic model suitable for sorafenib in HCC.

Sorafenib plus low-dose cisplatin and fluorouracil hepatic arterial infusion chemotherapy versus sorafenib alone in patients with advanced hepatocellular carcinoma (SILIUS): a randomised, open label, phase 3 trial

BACKGROUND Hepatic arterial infusion chemotherapy plus sorafenib in phase 2 trials has shown favourable tumour control and a manageable safety profile in patients with advanced, unresectable hepatocellular carcinoma. However, no randomised phase 3 trial has tested the combination of sorafenib with continuous arterial infusion chemotherapy. We aimed to compare continuous hepatic arterial infusion chemotherapy plus sorafenib with sorafenib alone in patients with advanced, unresectable hepatocellular carcinoma. METHODS We did an open-label, randomised, phase 3 trial (SILIUS) at 31 sites in Japan. Eligible patients were aged 20 years or older, with advanced hepatocellular carcinoma not suitable for resection, local ablation, or transarterial chemoembolisation; Eastern Cooperative Oncology Group (ECOG) performance status 0-1; Child-Pugh score 7 or lower; and adequate bone marrow, liver, and renal function. Patients were randomly assigned (1:1) via an interactive web response system with a computer-generated sequence to receive 400 mg sorafenib orally twice daily or 400 mg sorafenib orally twice daily plus hepatic arterial infusion chemotherapy (cisplatin 20 mg/m2 on days 1 and 8 and fluorouracil 330 mg/m2 continuously on days 1-5 and 8-12 of every 28-day cycle via an implanted catheter system). The primary endpoint was overall survival. The primary efficacy analysis comprised all randomised patients (the intention-to-treat population), and the safety analysis comprised all randomised patients who received at least one dose of study treatment. This trial is registered with ClinicalTrials.gov, number NCT01214343. FINDINGS Between Nov 4, 2010, and June 10, 2014, 206 patients were randomly assigned (103 to the sorafenib group, 103 to the sorafenib plus hepatic arterial infusion chemotherapy group). One patient in the sorafenib plus hepatic arterial infusion chemotherapy group withdrew after randomisation. Median overall survival was similar in the sorafenib plus hepatic arterial infusion chemotherapy (n=102) and sorafenib monotherapy (n=103) groups (11·8 months [95% CI 9·1-14·5] vs 11·5 months [8·2-14·8]; hazard ratio 1·009 [95% CI 0·743-1·371]; p=0·955). Grade 3-4 adverse events that were more frequent in the sorafenib plus hepatic arterial infusion chemotherapy group than in the sorafenib monotherapy group included anaemia (15 [17%] of 88 vs six [6%] of 102), neutropenia (15 [17%] vs one [1%]), thrombocytopenia (30 [34%] vs 12 [12%]), and anorexia (12 [14%] vs six [6%]). INTERPRETATION Addition of hepatic arterial infusion chemotherapy to sorafenib did not significantly improve overall survival in patients with advanced hepatocellular carcinoma. FUNDING Japanese Ministry of Health, Labour and Welfare.