Aim The aim of this study was to investigate the therapeutic potential of sodium glucose cotransporter 2 inhibitor (SGLT2I) as an effective therapeutic option for non‐alcoholic fatty liver disease (NAFLD). Methods In this prospective study, nine patients with NAFLD complicated by type 2 diabetes mellitus (DM), were introduced to the regimen of canagliflozin 100 mg once daily for 24 weeks and were evaluated by liver histology at pretreatment and at 24 weeks after the start of treatment. The primary outcome was histological improvement, defined as a decrease in NAFLD activity score of one point or more without worsening in fibrosis stage. Glucose metabolism was evaluated based on the meal tolerance test. The usefulness of extracellular and exosome microRNA‐122 (miR‐122) as early predictors of histological improvement was investigated. Results All of the nine patients achieved histological improvement. Scores of steatosis, lobular inflammation, ballooning, and fibrosis stage decreased by 78%, 33%, 22%, and 33% at 24 weeks compared to the pretreatment, respectively. Six patients showed improvement in insulin resistance, and the other three patients showed partial improvement of insulin secretion function. Six patients, who showed a decrease in both extracellular and exosome miR‐122 ratios (the ratio of miR‐122 levels at 1 day after treatment to that at baseline), showed histological improvement. Furthermore, one patient, who showed a decrease in exosome miR‐122 ratios regardless of the increase in extracellular miR‐122 ratios, also showed decreases in NAFLD activity score and fibrosis stage. Conclusion A prospective study showed that SGLT2I for NAFLD complicated by DM improved histological features in connection with glucose metabolism. This trial was registered as clinical trial UMIN000018166.

Anti‐programmed cell death‐1 (PD‐1) antibody therapy induces various adverse effects, especially in the endocrine system. Several cases of acute‐onset insulin‐dependent diabetes after anti‐PD‐1 antibody therapy have been reported. Many of these cases have a susceptible human leukocyte antigen (HLA) genotype for type 1 diabetes, possibly suggesting that HLA might be involved in the onset of diabetes with anti‐PD‐1 therapy. We describe an atypical case of hyperglycemia after anti‐PD‐1 antibody administration. A 68‐year‐old Japanese man with pancreatic diabetes and steroid diabetes was given nivolumab three times for chemoresistant adenocarcinoma of the lung. On day 5 after the third infusion of nivolumab, he had hyperglycemia (blood glucose 330 mg/dL and hemoglobin A1c 8.0%) without ketosis and with incompletely deficient insulin secretion. The patient had both type 1 diabetes susceptible (HLA‐A*24:02 and ‐DRB1*09:01) and resistant (HLA‐DRB1*15:02) HLA genotypes. These HLA genotypes differ from those previously reported in anti‐PD‐1 antibody‐induced diabetes, and might have influenced the preservation of insulin secretion after nivolumab administration in the present case.

Bax is considered as a main effector of apoptosis. Bax forms homodimers and also heterodimers with Bcl-2. The function of the Bax-Bax dimer in active cell death is antagonized by Bax-Bcl-2 heterodimers. Thus, the ratio of Bcl-2 and Bax should control the susceptibility of cells to those stimuli that induce apoptotic cell death. An increase in apoptotic change has been shown in many carcinomas. In the present study, the changes in Bcl-2 and Bax expression in the tissue during carcinogenic transformation were examined immunohistochemically by means of the 4-nitroquinoline 1-oxide (4NQO)-induced carcinoma model. Animals were divided into 7 groups of 10 rats each, and given 50 ppm 4NQO solution as drinking water for 4, 8, 12, 16, 20, or 24 weeks. Ten animals were used as controls. Gradual increases in the numbers of Bcl-2- and Bax-positive cells were shown corresponding to the progression of experimental carcinogenesis. Statistically significant differences in Bcl-2 and Bax expression were demonstrated between control and four-week treatment groups (p < 0.01), and between control and eight-week treatment groups (p < 0.05), respectively. Levels of both proteins remained high after the period of dysplastic change of the epithelium. In conclusion, Bcl-2 and Bax are involved in the progression of 4NQO-induced carcinoma.

The aim of this study was to delineate clinical features and prognosis of cancer of the gallbladder associated with anomalous junction of the pancreatobiliary duct system without bile duct dilatation, and to determine methods for managing the disease. A retrospective study of seven patients is presented. A further 27 cases from the Japanese literature were reviewed retrospectively with regard to method of treatment and prognosis. In 11 of 18 patients in whom staging was known the tumour was stage V, representing advanced disease. In seven of 34 cases curative operation was performed; only two patients survived for > 3 years. This poor outcome was due largely to delayed diagnosis of cancer of the gallbladder. Prophylactic cholecystectomy is recommended in patients with this anomalous junction without bile duct dilatation or a malignant lesion in the gallbladder, because of the high incidence of cancer of the biliary tract.

Slowly progressive type 1 insulin-dependent diabetes mellitus (SPIDDM), sometimes referred to as latent autoimmune diabetes in adults (LADA), is a heterogeneous disease that is often confused with type 1 and type 2 diabetes. As a result, there were few diagnostic criteria for this disorder until 2012, when the Japan Diabetes Society established criteria that could be used in clinical practice. A primary question is whether pathologic markers for type 1 or type 2 diabetes are present in the pancreas of patients with SPIDDM, because the phenotype of SPIDDM is similar to both type 1 and type 2 diabetes. Recent studies clarified pathologic findings in the pancreas of patients with SPIDDM, which included T-cell-mediated insulitis, a marker of type 1 diabetes; pseudoatrophic islets (islets specifically devoid of beta cells), another hallmark of type 1 diabetes; and a lack of amylin (ie, islet amyloid polypeptide) deposition to the islet cells, a pathologic marker of type 2 diabetes. In terms of preventing the loss of beta-cell function in patients with SPIDDM, several studies have shown that some drugs, including dipeptidyl peptidase-4 inhibitors, are effective. There is an increased need for early diagnosis of SPIDDM to preserve beta-cell function. This review presents updated findings on the pathogenesis and immunologic findings of the affected pancreas, diagnostic markers, risk factors for progression of beta-cell dysfunction, epidemiology, clinical features, diagnostic strategies, prevention strategies, and clinical options for patients with SPIDDM.