Rationale and design of a multicenter, single-group, open-label trial aiming at investigating the effectiveness of elobixibat for loss of defecation desire in patients with chronic constipation.

Background: Approximately 60% of patients with chronic constipation (CC) have a significantly higher rate of loss of defecation desire (LODD). Bile acids are expected to have a restorative effect on defecation desire (DD) because they lower the rectal sensory threshold, which is an objective index of DD. Elobixibat (EXB) specifically inhibits the ileal bile acid transporter/apical sodium-dependent bile acid transporter, which is a transporter involved in the reabsorption of bile acids in the terminal ileum. This study aims to investigate the LODD improvement rate in patients with CC after 4 weeks of EXB treatment. Methods: A total of 40 adult patients with CC who meet the eligibility criteria will be enrolled. Patients will receive oral EXB (10 mg/day) for 4 weeks. A patient diary will be provided daily at 4 weeks after treatment. The primary endpoint will be the percentage LODD improvement at week 4 of the treatment period from week 2 of the observation period using questionnaires. Ethics and dissemination: Ethical approval was obtained from the Yokohama City University Certified Institutional Review Board prior to participant enrolment (approval number: CRB21-008). The results of this study will be submitted for publication in international peer-reviewed journals, and key findings will be presented at international scientific conferences. Participants desiring the results of this study will be directly contacted for data dissemination. Trial registration: This trial was registered at ClinicalTrials.gov (NCT05165199). Protocol version: 1.0, September 21, 2021.

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.

Comparison of computed tomography findings with clinical risks factors for endoscopic therapy in upper gastrointestinal bleeding cases.

Several risk scoring systems exist for acute upper gastrointestinal bleeding (UGIB). The clinical Rockall score (clinical RS) and the Glasgow-Blatchford score (GBS) are major risk scores that consider only clinical data. Computed tomography (CT) findings are equivocal in non-variceal UGIB. We compared CT findings with clinical data to predict mortality, rebleeding and need for endoscopic therapy in non-variceal UGIB patients. This retrospective, single-center study included 386 patients admitted to our emergency department with diagnosis of non-variceal UGIB by urgent endoscopy between January 2009 and March 2015. Multivariable logistic regression analysis was used to investigate CT findings and risk factors derived from clinical data. CT findings could not significantly predict mortality and rebleeding in non-variceal UGIB patients. However, upper gastrointestinal hemorrhage in CT findings better predicted the need for endoscopic therapy than clinical data. The adjusted odds ratios were 10.10 (95% CI 5.01-20.40) for clinical RS and 10.70 (95% CI 5.08-22.70) for the GBS. UGI hemorrhage in CT findings could predict the need for endoscopic therapy in non-variceal UGIB patients in our emergency department. CT findings as well as risk score systems may be useful for predicting the need for endoscopic therapy.

Comparison of the early effects of vonoprazan, lansoprazole and famotidine on intragastric pH: a three-way crossover study.

To promote symptom relief from acid-related diseases, a medicine with a rapid-onset effect is ideal. The aim of this study was to investigate the early inhibitory effect on gastric acid secretion after a single oral administration of vonoprazan, which represents a new class of proton pump inhibitors, and to compare this effect with those of lansoprazole and famotidine. Ten Helicobacter pylori (HP)-negative male subjects participated in this randomized, three-way crossover study. A single oral administration of vonoprazan (20 mg), lansoprazole (30 mg) or famotidine (20 mg) was performed, and the intragastric pH was continuously monitored for 6 h. Each drug was administered at least seven days apart. The average intragastric pH during the 6-h period after the administration of famotidine was higher than that after the administration of lansoprazole (median: 4.45 vs 2.65; p = 0.0284). A similar result was observed for vonoprazan and lansoprazole (median: 4.30 vs 2.65; p = 0.0322). In conclusions, oral administration of vonoprazan and famotidine in HP-negative healthy male subjects caused the intragastric pH to rise more quickly than did lansoprazole. (Trial Registration: UMIN000020989).

Assessment of colonic contents in patients with chronic constipation using MRI.

Although chronic constipation is common, colonic functional evaluating tests are uncommon. This study examines whether chronic constipation and gastrointestinal symptoms are correlated with the lateral diameter of the colon measured from MRI images. We included chronic constipation patients in a prospective, cross-sectional study using MRI at three centers. We divided 3D MRI colorectal images into 6 segments using with specified sequences and selected the maximum luminal diameter from each segment. We used the GSRS questionnaire to evaluate gastrointestinal symptoms. We evaluated the correlation between luminal diameters and GSRS scores. We found the following positive correlations: descending colon and unsatisfactory defecation symptoms; sigmoid colon and diarrhea; and rectum and constipation. The sum and ratio of the ascending and sigmoid colon diameters correlated with nausea and diarrhea. The sum of the transvers to the sigmoid colon diameter also correlated with nausea and diarrhea. The sum of all segment diameters correlated with nausea and constipation. In conclusion, we showed cross-sectional study of colonic MRI correlate with gastrointestinal symptoms. MRI might be useful for colonic motility evaluations to determine appropriate constipation treatments (Clinical trial registry number UMIN 000021274).

The α-glucosidase inhibitor voglibose stimulates delayed gastric emptying in healthy subjects: a crossover study with a 13C breath test.

The gastrointestinal effects of α-glucosidase inhibitors have not been sufficiently investigated. The aim of this study was to determine whether a single dose of pre-prandial voglibose might affect the rate of gastric emptying, determined using the 13C breath test. Ten healthy male volunteers participated in this randomized, two-way crossover study. The subjects fasted overnight and received 0.2 mg voglibose or a placebo 2 h before a test meal. They were then served a liquid test meal consisting of 200 kcal per 200 ml that contained 100 mg 13C-acetate. Breath samples were collected under both conditions until 150 min after the meal. A comparison of the control and voglibose conditions revealed that for gastric emptying rates (with values expressed as median: range), T1/2 [(87.9: 78.0-104.9 min) vs (88.4: 74.3-106.3 min), p = 1], Tlag [(47.1: 39.6-60.1 min) vs (45.4: 31.2-63.3 min), p = 0.432], ß [(1.89: 1.68-2.18) vs (1.90: 1.35-2.15), p = 0.846] and κ [(0.81: 0.71-0.98) vs (0.81: 0.50-0.94), p = 0.922] did not significantly differ between conditions. A significant difference between the control and voglibose conditions was found for the GEC [(4.28: 4.09-4.44) vs (4.06: 3.69-4.50), p = 0.0138]. In conclusion, this study demonstrated that the ingestion of oral voglibose led to delayed gastric emptying of a liquid meal.

Early effect on intragastric pH of oral administration of rabeprazole with mosapride compared with rabeprazole alone.

BACKGROUND: An ideal medication for acid-related diseases would offer prompt stopping of blood flow as well as efficient symptom resolution. The aim of this study was to investigate the gastric acid suppression potency of a single oral dose of rabeprazole alone, compared with administration of rabeprazole plus mosapride. METHODS: Twelve male volunteers, Helicobacter pylori (H. pylori)-negative, participated in this randomized, three-way crossover study. After a single oral administration of rabeprazole, rabeprazole with mosapride, or rabeprazole administered 1 h after mosapride, we monitored their intragastric pH constantly for 6 h. A 7-day washout period was allowed between each administration. RESULTS: The median 6-h intragastric pH after the administration of rabeprazole 1 h after mosapride was 4.41±1.22 (mean±s.d.), significantly higher than after rabeprazole alone 3.45±1.33, P=0.0376). There was no significant difference between the median 6-h pH after the administration of rabeprazole plus mosapride and that after rabeprazole alone (3.81±0.98 vs. 3.45±1.33, respectively; P=0.0927). CONCLUSION: An oral dose of rabeprazole administered 1 h after mosapride increased the intragastric pH more rapidly than rabeprazole alone, in healthy, male, H. pylori-negative volunteers.

Evaluation of endoscopic findings for discriminating between early carcinomas and low-grade adenomas in superficial elevated gastric lesions.

BACKGROUND/AIMS: This study aimed to determine the useful endoscopic findings in a differential diagnosis between early carcinomas (EC) and low-grade adenomas (LGA) in superficial elevated gastric epithelial neoplasia during conventional endoscopy with white-light imaging (C-WLI). MATERIALS AND METHODS: We investigated 270 consecutive cases of superficial elevated gastric epithelial neoplasias, which were removed by endoscopic submucosal dissection. The pathological diagnostic criteria were based on the revised Vienna classification: category 4 (mucosal high-grade neoplasia) or 5 (submucosal invasion by carcinoma) lesions were diagnosed as EC, while category 3 (mucosal low-grade neoplasia) lesions were diagnosed as LGA. The association between the postoperative pathological diagnoses (EC or LGA) and the following endoscopic findings: localized site, lesion size, color (reddish or whitish), shape (smooth, petal, or irregular), and presences of depression, erosion, ulceration, or nodularity on the surface, were evaluated. RESULTS: Of 270 epithelial neoplasias, 222 (58 LGA and 164 EC) were retrospectively evaluated. Multiple logistic regression analysis revealed that the lesion size [odds ratio (OR), 1.216; p<0.001) and reddish color (OR, 5.274; p<0.001) were independent findings for EC. CONCLUSION: The lesion size and reddish color were useful optical findings for discriminating between EC and LGA.