Objective: Recent guidelines propose that both proton pump inhibitor (PPI) responders and nonresponders are included in eosinophilic esophagitis (EoE). Although multiple biopsies should be required to diagnose EoE because of patchy distribution of esophageal eosinophils, it is unclear whether multiple biopsies are required to evaluate histological effectiveness of PPI therapy. This study aimed to determine the optimal biopsy protocol after PPI therapy in patients with EoE. Methods: Of 110 EoE patients, 22 PPI nonresponders were enrolled. Intraepithelial eosinophils were counted in areas of high density in multiple biopsy specimens after PPI therapy. The prevalence of esophageal eosinophilia and peak eosinophil counts after PPI therapy was analyzed according to the biopsy sites and endoscopic findings. Positive predictive value (PPV) was calculated according to the number of biopsies. Results: Of 124 biopsies, 59 (47.6%) specimens showed esophageal eosinophilia (≥15 per high-power field). Eosinophil counts were significantly higher in specimens from the lower esophagus than in those from the upper esophagus but not in those from the middle esophagus. Prevalence of esophageal eosinophilia was 76.2, 40.9, and 24.3% in the lower, middle, and upper esophagus respectively. PPI nonresponders were diagnosed in all cases with 4 biopsy specimens obtained from the lower and middle esophagus, showing that PPV for non-effectiveness of PPI therapy was 0.910 (95% CI 0.773–1.000). The prevalence of esophageal eosinophilia and peak eosinophil counts was higher in cases with white plaques and linear furrows. Conclusion: Multiple biopsies should be required to evaluate histological effectiveness of PPI therapy in patients with EoE. Four biopsies from the lower and middle esophagus may be sufficient.

INTRODUCTION: No bowel preparation (BP) for colonoscopy achieves optimal efficacy and tolerability. Combining polyethylene glycol plus ascorbic acid (PEG-Asc) with adjuvants has been explored to enhance cleansing efficacy and reduce the required volume. The aim of this study was to evaluate whether adding 0.5 mg linaclotide to 1 L PEG-Asc (1 L-PEG/AL) improves superior cleansing compared with adding 24 mg senna (1 L-PEG/AS), which we previously reported to be noninferior to the standard regimen of 2 L PEG-Asc. METHODS: A multicenter, endoscopist-blinded, randomized controlled trial was conducted at 5 centers in Japan with outpatients scheduled for colonoscopy. The primary outcome was adequate BP, evaluated using the Boston Bowel Preparation Scale. Analyses were stratified based on low-risk and high-risk groups for inadequate BP. RESULTS: Between April 2022 and April 2023, 1,464 patients were randomized to the 1L-PEG/AL (n = 731) or 1L-PEG/AS (n = 733). The 1L-PEG/AL demonstrated higher adequate BP rates (92% vs 86%, P = 0.001) compared with 1L-PEG/AS. Both groups experienced similar adverse events and expressed high willingness for repeat BP (83% vs 81%, P = 0.49). In high-risk patients (n = 892), 1L-PEG/AL had significantly higher adequate BP rates (94% vs 86%, P < 0.001), whereas rates were comparably high in low-risk patients (n = 539) (94% vs 94%, P = 0.66). DISCUSSION: The linaclotide regimen was superior to the senna regimen reagrding BP efficacy without reducing tolerability. It can be a promising new option for BP, especially in patients at a high risk of inadequate BP.

Gastroesophageal reflux disease (GERD) is a common upper gastrointestinal disease. However, the role of exosomal microRNAs (miRNAs) and esophageal miRNAs in GERD has not been studied. A rat model of acid reflux esophagitis was used to establish a novel diagnosis marker for GERD and examine dynamics of miRNA expression in GERD. Rats were sacrificed 3 (acute phase), 7 (sub-acute phase) and 21 days (chronic phase) after induction of esophagitis. Exosomes were extracted from serum, and the expression patterns of serum miRNAs were analyzed. Four upregulated miRNAs (miR-29a-3p, 128-3p, 223-3p and 3473) were identified by microarray analysis. The expression levels of exosomal miR-29a-3p were significantly higher in the chronic phase of reflux esophagitis compared with controls, and increased expression of miR-29a-3p was specific to chronic reflux esophagitis. Esophageal miR-223-3p expression was higher compared with controls, and gradually decreased from acute to chronic phase in esophagitis. In conclusion, exosomal miR-29a-3p and esophageal miR-223-3p might play roles in GERD.

Constipation has been considered the key risk factor for diverticulosis occurrence, but the underlying mechanism is unclear. We investigated the factors associated with diverticulosis, focusing on ...

Approximately half of patients with eosinophilic esophagitis (EoE) respond clinically and histologically to proton pump inhibitor (PPI) therapy. Although recent guidelines suggest that PPI-responders and non-responders were included in EoE, it is important to investigate the predictive factors of PPI- responsiveness. This study aimed to determine the rate of PPI- responders and compare the characteristics of PPI-responders and non-responders. Fifty-nine patients with esophageal eosinophilia received PPI therapy for eight weeks, and its efficacy was assessed. PPI- responsiveness was diagnosed based on the relief in symptoms and reduction of intraepithelial eosinophilic infiltration to <15 per high-power field (hpf) after PPI therapy. Multivariate analysis was performed to identify factors associated with PPI-responders. Of the 59 patients, 41 (69.5%) were diagnosed with PPI-responders. The rate of gastrointestinal (GI) screening in the indications for endoscopy was significantly higher in patients with PPI- responders than in those with non-responders. On multivariate analysis, GI screening and presence of reflux esophagitis was associated with an increased odds ratio (OR) of PPI-responders, but presence of rings with a decreased OR of PPI-responders. Presence of reflux esophagitis and absence of rings on endoscopy especially during GI screening might be significant predictive factors for PPI response in patients with EoE.