ObjectiveReal-life safety and efficacy of sorafenib in advanced renal cell carcinoma in a nationwide patient population were evaluated by post-marketing all-patient surveillance.MethodsAll patients with unresectable or metastatic renal cell carcinoma in Japan who started sorafenib therapy from February 2008 to September 2009 were registered and followed for up to 12 months. Baseline characteristics, treatment status, tumor response, survival and safety data were recorded by the prescribing physicians.ResultsSafety and efficacy were evaluated in 3255 and 3171 patients, respectively. The initial daily dose was 800 mg in 78.2% of patients. Median duration of treatment was 6.7 months and the mean relative dose intensity was 68.4%. Overall, 2227 patients (68.4%) discontinued the treatment by 12 months, half of which (52.0% of discontinued patients) were due to adverse events. The most common adverse drug reactions were hand–foot skin reaction (59%), hypertension (36%), rash (25%) and increase in lipase/amylase (23%). The median progression-free survival was 7.3 months (95% confidence intervals: 6.7–8.1), and the overall survival rate at 1 year was 75.4% (73.5–77.1). Prognostic factors for overall survival were mostly consistent with those in previous clinical trials in the univariate analysis and largely similar to those for progression-free survival and duration of treatment in the multivariate analysis.ConclusionsSorafenib for the treatment of advanced renal cell carcinoma under the labeled dose was feasible in daily medical practice, for its acceptable toxicity profile and favorable clinical benefit that were consistent with those in clinical trials.

Acute gastroenteritis associated with diarrhea is considered a serious disease in Africa and South Asia. In this study, we examined the trends in the causative pathogens of diarrhea and the corresponding gut microbiota in Ghana using microbiome analysis performed on diarrheic stools via 16S rRNA sequencing. In total, 80 patients with diarrhea and 34 healthy adults as controls, from 2017 to 2018, were enrolled in the study. Among the patients with diarrhea, 39 were norovirus-positive and 18 were rotavirus-positive. The analysis of species richness (Chao1) was lower in patients with diarrhea than that in controls. Beta-diversity analysis revealed significant differences between the two groups. Several diarrhea-related pathogens (e.g., Escherichia-Shigella, Klebsiella and Campylobacter) were detected in patients with diarrhea. Furthermore, co-infection with these pathogens and enteroviruses (e.g., norovirus and rotavirus) was observed in several cases. Levels of both Erysipelotrichaceae and Staphylococcaceae family markedly differed between norovirus-positive and -negative diarrheic stools, and the 10 predicted metabolic pathways, including the carbohydrate metabolism pathway, showed significant differences between rotavirus-positive patients with diarrhea and controls. This comparative study of diarrheal pathogens in Ghana revealed specific trends in the gut microbiota signature associated with diarrhea and that pathogen-dependent dysbiosis occurred in viral gastroenteritis.

Sorafenib (Nexavar) is an oral multi-kinase inhibitor that targets tumor growth and angiogenesis, having encouraging efficacy and tolerability in patients with metastatic renal cell carcinoma (RCC) and other tumors. However, hand-foot syndrome (HFS), a frequently reported adverse event under sorafenib treatment, sometimes causes interruption of the treatment or dose reduction. This study was conducted to review sorafenib-associated HSF in Japanese patients, to facilitate improvement of the management of HFS in clinical practice. We reviewed the combined results on HFS in three sorafenib studies in Japanese patients: (A) a phase II study of metastatic renal cell carcinoma; (B) a phase I study of solid tumor; and (C), phase I study of hepatocellular carcinoma. Severity of HFS was graded as 1-3 based on the modified grading scale of National Cancer Institute -Common Toxicity Criteria version 2.0 and Common Terminology Criteria for Adverse Events version 3.0. A total of 189 patients were included for analyses. The incidence of all-grade HFS was 51% (55% in A, 39% in B and 44% in C), and the incidence of grade 3 HFS was 7% (9% in A, 0% in B and 7% in C). Incidence of HFS seemed dose-dependent. These events were observed within 3-9 weeks after initiation of sorafenib treatment. The majority of HFS was manageable with symptomatic treatment and HFS caused permanent discontinuation of sorafenib in only one patient (in study A). The incidence of sorafenibassociated HFS is high compared to other adverse events. However, the present analyses showed that HFS under sorafenib treatment is well manageable in Japanese patients.

The examination of congenital malaria was performed by Giemsa staining and polymerase-chain-reaction (PCR) methodology. We randomly selected 298 neonates who had been admitted to Muhimbili Medical Center (MMC) at Dar es Salaam, Tanzania. One baby among all the enrolled neonates was recognized as having a congenital malaria infection, which gave a prevalence of 0.33%. The present result was 5-fold the clinically recognized prevalence of congenital infection with malaria in the ward. The PCR method identified two cases, one of which was negative as determined by the Giemsa-staining method. Therefore, the PCR method was useful for the detection of scant amounts of malarial parasites in numerous blood samples. The screening of malaria by a sensitive PCR method contributes to reduce the mortality of asymptotic neonates in particular.

Angioleiomyoma in the buccal space is a less common benign neoplasm. To the best of our knowledge, only two cases have been described. We herein describe a new case of angioleiomyoma in the buccal space of a 45-year-old Japanese woman. No specific features were observed on clinical examination or ultrasonography. With an initial diagnosis of an ectopic lymph node or benign tumor, excision via the oral cavity was performed under local anesthesia. Healing was uneventful. Immunohistochemical examination revealed that the excised specimen was progesterone receptor-positive and estrogen receptor-negative.