坂本 博次

BACKGROUND: Vonoprazan (VPZ) therapy has become one of the standard treatments for gastroesophageal reflux disease (GERD). When GERD symptoms persist despite the maintenance dose therapy (10 mg daily), dose escalation to 20 mg daily is generally recommended. This study aims to clarify the proper timing and predictors for dose escalation of VPZ therapy in patients with refractory GERD treated with the maintenance dose. METHODS: This retrospective observational study included 257 patients with symptomatic GERD. Data from medical records, including endoscopic findings and Izumo scale scores, were analyzed. RESULTS: The mean follow-up period was 3.3 years. Throughout the follow-up period, VPZ dose escalation (from 10 to 20 mg daily) was required in 56 of 257 patients (22%). Kaplan-Meier analysis showed cumulative dose-escalation-free rates at 6 months, 1 year, and 2 years were 87%, 81%, and 78%, respectively. Predictive factors for VPZ dose escalation were analyzed using a Cox proportional hazards regression model. Multivariate analysis revealed that pre-existing epigastric pain was a significant positive predictor for dose escalation, whereas pre-existing constipation was identified as a significant negative predictor. Kaplan-Meier analysis indicated that the one-year dose-escalation-free rates were 69% in patients with epigastric pain compared to 88% in those without (p=0.001). GERD symptom scores showed a significant improvement one month after dose escalation. CONCLUSION: The incidence of refractory GERD requiring VPZ dose escalation is relatively low. Epigastric pain prior to VPZ initiation independently predicts the need for dose escalation. VPZ dose escalation effectively improves GERD symptoms.

OBJECTIVES: Endoscopic balloon dilation (EBD) is an effective treatment for intestinal strictures in Crohn's disease (CD). However, restenosis often occurs and requires repeat EBD or surgery. Previous studies have seldom examined restenosis with respect to stricture diameter, leaving the factors contributing to post-EBD restenosis unclear. Our retrospective study indicated that complete mucosal healing significantly reduces restenosis after EBD in CD-related small intestinal strictures. This prospective study aimed to validate these findings by accurately measuring stricture diameters in patients with CD. METHODS: We conducted a single-center prospective study of patients with CD and small intestinal strictures. The patients underwent an EBD session between June 2022 and December 2023. Stricture diameters were measured using a calibrated small-caliber-tip transparent hood. Multivariate analysis was performed to identify factors influencing stricture progression. RESULTS: This study included 41 patients (33 men). The number of strictures detected between sessions increased from 159 to 170. The average diameter of all strictures and the narrowest stricture per patient showed slight increases. However, 73% of patients experienced stricture progression. The presence of ulcers between sessions was identified as a significant risk factor for stricture progression (odds ratio 7.59, p = 0.031). Patients achieving complete mucosal healing demonstrated a significant increase in the narrowest stricture diameter (+1.5 mm, p = 0.00089). CONCLUSIONS: Complete mucosal healing is crucial for preventing stricture progression after EBD in patients with CD-related small intestinal strictures.

Gastric mucosal changes associated with long-term potassium-competitive acid blocker and proton pump inhibitor (PPI) therapy may raise concern. In contrast to that for PPIs, the evidence concerning the safety of long-term potassium-competitive acid blocker use is scant. Vonoprazan (VPZ) is a representative potassium-competitive acid blocker released in Japan in 2015. In order to shed some comparative light regarding the outcomes of gastric mucosal lesions associated with a long-term acid blockade, we have reviewed six representative gastric mucosal lesions: fundic gland polyps, gastric hyperplastic polyps, multiple white and flat elevated lesions, cobblestone-like gastric mucosal changes, gastric black spots, and stardust gastric mucosal changes. For these mucosal lesions, we have evaluated the association with the type of acid blockade, patient gender, Helicobacter pylori infection status, the degree of gastric atrophy, and serum gastrin levels. There is no concrete evidence to support a significant relationship between VPZ/PPI use and the development of neuroendocrine tumors. Current data also shows that the risk of gastric mucosal changes is similar for long-term VPZ and PPI use. Serum hypergastrinemia is not correlated with the development of some gastric mucosal lesions. Therefore, serum gastrin level is unhelpful for risk estimation and for decision-making relating to the cessation of these drugs in routine clinical practice. Given the confounding potential neoplastic risk relating to H. pylori infection, this should be eradicated before VPZ/PPI therapy is commenced. The evidence to date does not support the cessation of clinically appropriate VPZ/PPI therapy solely because of the presence of these associated gastric mucosal lesions.

The appearance of 'web-like mucus' in the stomach is a novel phenomenon associated with vonoprazan (VPZ) usage, characterized by a descriptive mucus pattern resembling a spider web or net. The present study aimed to determine its prevalence and related factors. In this retrospective observational study, the medical records and endoscopic reports of 547 patients who underwent an esophagogastroduodenoscopy were reviewed. The overall prevalence of web-like mucus was 6% (33/547), with 97% (32/33) of these patients being VPZ users. Specifically, 19% (32/167) of VPZ users exhibited this web-like mucus pattern, which was significantly more prevalent in the VPZ group than in the control (no acid blocker intake), proton pump inhibitor, and histamine-2 receptor antagonist groups. Multivariate analysis identified that VPZ use was positively associated with web-like mucus, while open-type gastric atrophy and multiple white and flat elevated lesions were negatively associated. A retrospective analysis of endoscopic findings before initiating VPZ therapy showed that none of the 32 VPZ users with web-like mucus had exhibited the pattern previously. Furthermore, the Cochran-Armitage trend test indicated no significant association between the duration of VPZ therapy and the prevalence of web-like mucus. In conclusion, web-like mucus in the stomach is strongly associated with VPZ use but is not associated with the duration of VPZ therapy.