Effect of vonoprazan on the treatment of artificial gastric ulcers after endoscopic submucosal dissection: Prospective randomized controlled trial.

BACKGROUND AND AIM: Proton pump inhibitors are effective for the treatment of gastric ulcers after endoscopic submucosal dissection (ESD). However, the most excellent therapy is controversial. Vonoprazan, an active potassium-competitive acid blocker, has a strong gastric acid secretion inhibitory effect, but its efficacy for the treatment of post-ESD gastric ulcers is unclear. Herein, we aimed to determine the healing effect of vonoprazan on post-ESD gastric ulcers. METHODS: We carried out a prospective randomized controlled trial examining 92 patients who had undergone ESD for the treatment of gastric neoplasms between April 2015 and June 2016 at Machida Municipal Hospital. Patients were treated with 20 mg/day vonoprazan (V group) or 20 mg/day esomeprazole (E group) for 8 weeks. We evaluated the 8-week cure rate for artificial ulcers and any complications after ESD. RESULTS: A total of 80 patients (median age, 73.5 years; 71.3% male) were analyzed. Cure rate for the V group was significantly higher than that for the E group (94.9% [37/39] vs 78.0% [32/41], respectively; P = 0.049). In a multivariate analysis, only vonoprazan was correlated with ulcer healing (odds ratio = 6.33; 95% CI = 1.21-33.20; P = 0.029). Delayed bleeding was experienced only in the E group (7.3% [3/41]), but no significant difference compared with the V group was observed (P = 0.241). CONCLUSION: Vonoprazan was significantly superior to esomeprazole for the healing of post-ESD gastric ulcers and should be considered as a treatment of first choice.

[Disseminated varicella-zoster virus infection complicated with severe abdominal pain and colonic pseudo-obstruction].

A 48-year-old man was admitted to our hospital complaining of acute severe abdominal pain and constipation. He had received bone marrow transplantation for acute myelogenous leukemia 5 months previously and immunosuppressant treatment for chronic graft-versus-host disease. Abdominal X-ray and CT scan films revealed his large intestine widely dilated and filled with air, and colonic pseudo-obstruction was diagnosed. It was difficult to ascertain the cause of the symptoms until 6 days after onset of the abdominal pain when disseminated zoster eruption appeared over his whole body. It was disseminated varicella-zoster and complicated with colonic pseudo-obstruction. He was treated with acyclovir. It is important to suspect disseminated varicella-zoster and treat early immunocompromised patients complaining of severe acute abdominal pain and colonic pseudo-obstruction.

Percent reduction of the ulcer size at 4 weeks is a predictor of the complete healing of endoscopic submucosal dissection-induced gastric ulcers.

BACKGROUND AND STUDY AIMS: Endoscopic submucosal dissection (ESD) is widely used as a treatment modality for gastric mucosal neoplasia. While proton pump inhibitors (PPIs) have been used for the control of artificial ulcers created by ESD (ESD-ulcers), complete healing of the ulcers is not always achieved in all the cases. The purpose of this study was to identify the clinical factors that are predictive of refractory ESD-ulcers. PATIENTS AND METHODS: We recruited 90 patients with 102 artificial ulcers that formed after the patients underwent ESD for gastric tumours. All the patients received a 20-mg capsule of esomeprazole daily until the 56th day after ESD, and underwent endoscopy at 1, 4, 6 and 8 weeks after the ESD. We analyzed the clinical factors that were associated with the complete healing at 8 weeks after the ESD (CH-8w). The ulcers in the scar stage were defined as the complete healing in this study. RESULTS: Of the 102 ESD-ulcers, 16.7% failed to show complete healing after the 8 weeks of PPI therapy. Univariate analysis identified the percent reduction of the ulcer size at 4 weeks after ESD (PR-4w) as being significantly associated with CH-8w. Multivariate analysis identified ulcer location in the lower-third of the stomach and PR-4w > 95% as being independently correlated with the CH-8w (odds ratio = 4.86 and 7.89, respectively). Analysis of the area under the receiver operating characteristic (AUROC) curve demonstrated that the AUROC curve of PR-4w for predicting the CH-8w was 0.78. CONCLUSION: Based on the results of our study, endoscopic observation at 4 weeks after ESD would help in the early identification of refractory ESD-ulcers.

Treatment with Anti-FcεRIα (MAR-1) Antibody Prevents Acute Islet Allograft Rejection in a Murine Model.

OBJECTIVE: Various immunological strategies for tolerance induction against allogeneic tissue grafts (allografts) have been tested in islet transplant recipients; for example, T cell activating co-stimulatory pathway blockade has been shown to prolong islet allograft survival. However, little is known about whether infiltrating inflammatory cells (e.g., basophils) affect islet allograft fates before antigen-specific immune cell development. Herein, we treated mice with a basophil-specific monoclonal antibody (mAb) and examined whether early acute-phase islet allograft rejection could be prevented in recipients. METHODS: Pancreatic islets isolated from C57BL/6 (H-2b) or DBA/2 (H-2d) mice were transplanted under the renal capsules of C57BL/6 recipient mice. Recipients receiving allografts were administered the anti-basophil mAb MAR-1 to examine the antibody-mediated effect on graft survival. At days 4 and 7 post-transplantation, graft-bearing recipient kidneys were harvested for immunohistological analysis and stained with anti-insulin antibody to compare the sizes of grafted islets. RESULTS: On day 7 post-transplantation, the transplanted pancreatic islet clusters in allograft-recipient kidneys had rapidly decreased in size, whereas those in syngeneic recipients remained larger in both size and number. However, MAR-1-treated recipients had increased the numbers of larger insulin-positive allograft islet cell clusters. CONCLUSION: Basophil-specific mAb treatment contributes to enhance and prolong transplanted islet survival in allogeneic recipient mice.

Significant clinical response of advanced colon cancer to peptide vaccine therapy: a case report.

Partial response (PR) was obtained in a patient with advanced colon cancer following peptide vaccine therapy. A 61-year-old woman was referred to our hospital for peptide vaccine therapy. She had undergone sigmoidectomy at a nearby hospital and eventually developed multiple metastases to the lung and pelvic lymph nodes with left hydronephrosis. A ureteral stenting catheter had been inserted for left hydronephrosis, and oral opioids had been administered for relief of pain in the left pelvic region. Three tumor-antigen-derived peptides (RNF43, TOMM34, and KOC1) and two human VEGFR-derived peptides (VEGFR1 and VEGFR2) were used as a cocktail. The peptide cocktail was subcutaneously inoculated on days 1, 8, 15, and 22 and repeated at 14-day intervals. The patient's serum level of carcinoembryonic antigen was 28.9 ng/mL (N<5 ng/mL) before treatment, and it decreased promptly after the initiation of therapy to within a normal range. Evaluation of computed tomography images at week 5 revealed PR as determined by the Response Evaluation Criteria in Solid Tumor criteria. After month 3, the oral opioid was discontinued. The PR lasted for 4 months and was followed by stable disease for another 4 months. No particular adverse effects were observed. A cytotoxic T lymphocyte (CTL) response was evaluated by immunosorbent spot assay, and a positive CTL response was recognized against at least one of five peptides at each end of the six courses. Immunotherapy has been proven to slow tumor growth by inducing an active antitumor immune response; and therefore, significant tumor shrinkage is rarely observed. To our knowledge, this is the first case report of PR presented in a patient with advanced colon cancer.

Notch signaling is necessary for GATA3 function in the initiation of T cell development.

GATA3 and Notch1 are essential for T cell development at the earliest stage, but their mutual roles in this process remain to be clarified. In this study, we demonstrated that impairment of T lymphopoiesis in hematopoietic progenitor cells (HPC) of GATA3-deficient fetal liver (FL) on day 11.5 of gestation (E11.5) was rescued only by introduction of both GATA3 and the intracellular region of Notch1 but not by either alone. However, the introduction of GATA3 only was sufficient for T cell induction in GATA3-deficient FL cells at the advanced stage, where Notch signaling is well detectable. This indicates that Notch signaling is necessary for GATA3 to function for T cell fate specification but is not sufficient without GATA3. On the other hand, Notch signaling is sufficient for blockage of B cell development without GATA3, suggesting that T cell fate specification at the branching point does not result simply from the developmental arrest of B cell lineage by Notch signaling.