Digestion最新文献

Background: Emerging evidence highlights the gut microbiota as a key contributor to the pathophysiology of irritable bowel syndrome (IBS), acting through complex interactions with intestinal motility, immune function, epithelial barrier integrity, and the gut-brain axis. This narrative review summarizes current knowledge regarding the roles of the gut microbiota and their metabolites in IBS.

Summary: We discuss alterations in the gut microbiota in IBS, with particular emphasis on changes in short-chain fatty acid production, bile acid metabolism, serotonin signaling, and gas handling. Special attention is given to microbial metabolites as mediators of visceral hypersensitivity, intestinal permeability, and neuromodulation within the microbiota-gut-brain axis. Major alterations in the gut microbiota of IBS are characterized by a reduction in Bacteroidetes, Bifidobacteria, and Faecalibacterium, accompanied by an increase in Firmicutes. We explain the importance of butyrate metabolism in colonic epithelial cells for maintaining the anaerobic environment of the gut. In addition, we review the impact of diet-microbiota interactions, including FODMAP restriction, resistant starch intake, and protein fermentation, on symptom generation and microbial stability.

Key message: Although accumulating evidence supports a link between gut dysbiosis and IBS, establishing causal relationships remains challenging due to disease heterogeneity and dietary influences. Future large-scale, well-phenotyped, multi-omics studies integrating microbiota, metabolomic, and host factors are required to elucidate underlying mechanisms and to guide personalized therapeutic strategies for IBS.

Background: For intermediate-sized (10-20 mm) superficial non-ampullary duodenal epithelial tumors (SNADETs), various endoscopic resection (ER) techniques are available, including conventional endoscopic mucosal resection (EMR), underwater EMR (UEMR), and endoscopic submucosal dissection (ESD). However, the optimal method remains uncertain.

Summary: We conducted a systematic review of studies published from January 2013 to August 2023 using PubMed and the Japan Medical Abstracts Society database. Eligible studies reported ER outcomes for SNADETs of ≤20 mm. Data were extracted from 14 cohort studies (3 multicenter of lesions 10-20 mm in size and 11 single-center of lesions less than 20 mm), including en bloc and R0 resection rates, delayed bleeding, intraoperative and delayed perforation, and recurrence. In the multicenter studies, the pooled en bloc resection rates for EMR, UEMR, and ESD of intermediate-sized SNADETs were 82.7%, 74.8%, and 94.6%, respectively. The corresponding R0 resection rates were 54.2%, 50.6%, and 80.9%. Delayed bleeding rates were similar across methods (3.3% for EMR, 3.2% for UEMR, and 5.4% for ESD). However, intraoperative and delayed perforation were more frequent with ESD (7.9% and 3.0%) than with EMR (1.1% and 0.3%) and UEMR (0.0% and 0.0%). Single-center studies showed consistent trends, with ESD achieving higher resection rates but also showing greater variability in adverse events. Recurrence rates were about 5% for EMR and UEMR, with no recurrences reported after ESD.

Key messages: While ESD provides superior resection quality, EMR and UEMR offer favorable outcomes with fewer adverse events. Given their safety and efficacy profiles, EMR and UEMR should be considered appropriate first-line treatment options for intermediate-sized SNADETs.

Introduction: A new, minimally invasive method is needed to evaluate both esophageal muscle contraction and esophageal wall distensibility under physiological conditions. The primary objective of this study was to establish a novel examination method for evaluating esophageal wall motion using a transnasal endoscope with an endoscopic ultrasonography (EUS) probe. The secondary objective was to apply this method to gain new pathophysiological insights into the clinical subtypes of achalasia diagnosed by high resolution manometry.

Methods: The study included 20 patients with dysphagia. Patients were instructed to swallow 20 ml of oral rehydration solution while a transnasal endoscope and a 20 MHz EUS probe were used to record the swallowing motion. The esophageal lumen area and muscle layer thickness were measured on still images from recorded videos. The reproducibility of the method was evaluated for both internal and external consistency. The study also analyzed differences in esophageal wall motion among achalasia subtypes using two new parameters: the muscle layer contraction rate and the esophageal wall distension rate.

Results: The new transnasal EUS method was safely performed in all 20 patients without complications, and the images were sufficient for analysis. The reproducibility evaluation showed significant positive correlations for both internal and external reproducibility. The esophageal wall distensibility and muscle layer contraction rates differed between esophageal achalasia subtypes.

Conclusions: This pilot study successfully established a new, safe, and reproducible method for evaluating esophageal wall motion using transnasal EUS. This method will lead to a deeper understanding of the pathophysiology of esophageal motility disorders and potentially to the development of new treatment strategies.

Introduction: High-risk chronic atrophic gastritis (CAG; OLGA/OLGIM Ⅲ-Ⅳ) carries significant gastric cancer (GC) risk yet lacks reliable gastric stem cell (GSC)-based biomarkers. We evaluated GSC markers LGR5 (proliferative) and TFF2 (protective) for risk stratification.

Methods: TCGA/GEO bioinformatics analysis preceded immunohistochemical validation in 60 clinical samples. Protein co-expression (Wnt/β-catenin, Ki67, Bax) was assessed. Diagnostic/prognostic power was tested via ROC and Kaplan-Meier analyses. Functional networks were deciphered through GO/KEGG enrichment.

Results: High-risk CAG and GC tissues showed LGR5 upregulation and TFF2 downregulation (p < 0.001). IHC confirmed these patterns, with concurrent Wnt activation (β-catenin↑, cyclin D1↑) and proliferation-apoptosis imbalance (Ki67↑, Bax↓). TFF2 outperformed LGR5 in diagnosing high-risk CAG (AUC: 0.842 vs. 0.681). Poor GC prognosis correlated with high LGR5/low TFF2 (p < 0.05). Co-expression networks linked LGR5 to metabolic genes (CPS1, ADH6) and TFF2 to mucosal defense (GKN1, PGC).

Conclusion: The coordinated assessment of LGR5 and TFF2 offers a promising approach to identifying high-risk CAG. This biomarker pair captures a homeostatic imbalance in GSCs linked to Wnt/β-catenin signaling, establishing a novel molecular framework for early detection and future targeted strategies.

Background: With the increasing proportion of the Helicobacter pylori (Hp)-naïve population in Japan, conventional Hp-infected gastric neoplasms (HpIGNs) have decreased, whereas Hp-naïve gastric neoplasms (HpNGNs) are being detected more frequently.

Summary: Hp infection remodels the gastric mucosa and promotes tumorigenesis through a high mutational burden and epigenetic dysregulation, contributing to the histologically diverse and aggressive nature of HpIGNs. In contrast, HpNGNs arise with few genetic and epigenetic alterations, resulting in limited morphological diversity determined by the type of their background mucosa. Most HpNGNs arise in the fundic gland mucosa and exhibit a gastric phenotype, whereas those arising from the pyloric gland mucosa or gastric cardia show a variable phenotype. Regardless of histologic subtype, HpNGNs are generally biologically indolent, except for a subset arising in the gastric cardia. The histological classification of HpNGNs does not always fit conventional diagnostic frameworks for gastric neoplasms. In particular, foveolar-type adenomas (FGAs) need to be subclassified into flat and raspberry types, which represent distinct molecular entities. Furthermore, HpNGNs with a MUC6-dominant gastric phenotype, including gastric adenocarcinomas of fundic gland or fundic gland mucosa type and some flat-type FGAs with partial MUC6-dominant components, and pyloric gland adenomas form a morphological and molecular continuum, occasionally making histological distinction difficult. A comprehensive disease concept integrating these lesions may help resolve this diagnostic issue.

Key messages: As the prevalence of Hp infection continues to decline worldwide, HpNGNs are expected to emerge as a distinct disease entity, highlighting the need for refined diagnostic frameworks and risk-based surveillance strategies in the post-Hp era.

Introduction: The fecal immunochemical test (FIT) is a wide available fecal biomarker that could evaluate the disease activity in inflammatory bowel disease (IBD). The aim was to assess the correlation between the FIT and fecal calprotectin (FC) for evaluating IBD activity.

Methods: This was a unicentric, transversal cohort study. Consecutive patients with IBD were included and FIT and FC were determined. The clinical activity was assessed with Truelove-Witts and Yamamoto-Furusho index for UC patients while Harvey-Bradshaw and CDAI for CD patients. Spearman's rank correlation test was used to assess the correlation between FIT and FC. Sensitivity, specificity, and positive (PPV) and negative predictive values (NPVs) for FIT and FC were calculated. Receiver operator curves were constructed.

Results: A total of 206 patients were included. One hundred forty-eight (72%) patients had diagnosis of UC and 58 (28%) with CD. The median of FIT was 2.8 μg/g (range, 2.6-2,394 μg/g) and the median for FC level was 265.5 μg/g (range, 22-6,285 μg/g). There was a very good correlation between FIT with and FC in UC patients (r_s = 0.745, p < 0.01) and moderate in CD patients (r_s = 0.574, p < 0.01). A FIT cutoff of 2.6 μg/g identified endoscopic activity in UC patients with a sensitivity of 78%, specificity of 86%, PPV of 91% and NPV of 67% with an area under the curve (AUC) of 0.852 (95% CI: 0.758-0.946).

Conclusion: FIT can be an alternative fecal biomarker to assess the disease activity in UC patients.

Introduction: European and National Celiac Disease (CeD) guidelines offer an easy pathway to diagnose CeD. The German CeD Registry aimed to assess symptoms and clinical findings before diagnosis, diagnostic delay, care during the diagnostic process, and factors associated with persistence of symptoms.

Methods: Individuals with CeD provided demographic, clinical, and healthcare-related information. Participants were divided into four subgroups according to age at diagnosis (>18 or <18 years) and year of diagnosis (before and since 2012). Factors associated with symptoms after at least 1 year on a gluten-free diet (GFD) were assessed using multivariate logistic regression.

Results: From 11/2019 to 10/2021, 2,333 participants were enrolled. After exclusion of 169 (7.2%), 2,164 remained for analysis, thereof 796 (36.8%) were diagnosed <18 years, and 1,283 (59.3%) since 2012. Most common symptoms before diagnosis included abdominal pain (83%), bloating (82%), fatigue (78%), and diarrhoea (71%). Diagnostic delay after 2012 was longer in adults than children (median 4.4 years [interquartile range; IQR: 1.2-13.0] versus 1.1 [IQR: 0.5-2.2], respectively) (p < 0.001). Guideline-conform diagnoses increased over time. After diagnosis, only 60% received professional dietary counselling. Factors associated with symptoms despite GFD included female gender (odds ratio [OR]: 1.79 [95% confidence interval: 1.34; 2.40], p < 0.001), same symptom before diagnosis (OR: 3.45 [2.45; 4.96], p < 0.001), insufficient information provided at diagnosis (OR: 1.25 [1.00; 1.57], p = 0.046), and age at diagnosis (per decade) (OR: 1.11 [1.04; 1.18], p < 0.001) but not time since diagnosis.

Conclusions: Our findings revealed deficits in awareness, the diagnostic process, and post-diagnostic care that are linked to decreased clinical improvement over time.

Introduction: The Mayo endoscopic score (MES) is used widely in ulcerative colitis (UC) for severity assessment and therapeutic decision-making. Deep learning (DL) models developed to determine MES currently lack explainability. We aimed to develop explainable models for the MES in patients with UC and examine the human-artificial intelligence interactions with the models.

Methods: This was a retrospective multicenter study conducted across four large tertiary institutions in China. A total of 2,600 white light images were used for training. Two approaches were adopted: traditional blackbox or explainable AI (XAI). The trained models were evaluated with three external test datasets (#1 Changshu and Jintan hospitals, n = 100; #2 HyperKvasir, n = 100; #3 Yongding hospital, n = 260), and the performance was compared with endoscopists. The primary outcome was the performance of 4-way classification. For explainability, moreover, Grad-CAM was for computer vision, while local interpretation, variable importance, and partial dependence plots were for the classifier within XAI.

Results: In the test #1 dataset, a Xception-backboned XAI showed accuracy of 0.910, Matthew's correlation coefficient 0.880, and Cohen's kappa 0.960 (95% CI, 0.940-0.990). The metrics were better than other models, as well as the two endoscopists. With the AI assistance, the performance of endoscopists were improved (senior's accuracy from 0.890 to 0.930 and junior's accuracy from 0.810 to 0.880). Similar trend was observed in the test #2 and #3 datasets.

Conclusion: The use of an explainable framework empowers AI models to achieve improved performance with transparency. XAI can also improve endoscopist performance in interpretation of MES in UC.

Introduction: In the surveillance of esophageal squamous cell carcinoma (ESCC), advanced lesions may still be detected despite regular screening with esophagogastroduodenoscopy (EGD). In this study, we investigated the endoscopic characteristics and prognosis of ESCC cases that progressed to pT1a-MM or deeper despite undergoing surveillance EGD.

Methods: We retrospectively analyzed 225 consecutive superficial ESCC lesions invading beyond the muscularis mucosa that were resected by endoscopic submucosal dissection (ESD) from 215 patients at Hiroshima University Hospital between April 2010 and March 2023. Among them, 28 patients (29 lesions) were classified as the post-EGD ESCC (PEESCC) group, defined as cases where surveillance EGD performed 24 months before diagnosis did not detect neoplasia or carcinoma. The remaining 188 patients (196 lesions) were the screening group. Subsequently, endoscopic findings and prognosis were compared.

Results: From the multivariate analysis, the presence of Lugol-voiding lesions (69.0% vs. 39.3%), cervical esophageal location (17.2% vs. 3.1%), small tumor diameter (21.6 ± 12.3 mm vs. 34.0 ± 18.3 mm), and submucosal tumor (SMT)-like elevation (20.7% vs. 7.7%) were significantly identified as characteristic endoscopic findings of PEESCC. The PEESCC group exhibited lower 5-year disease-specific survival (93.1% vs. 98.5%, p = 0.039) and recurrence-free survival (69.0% vs. 83.7%, p = 0.025).

Conclusion: PEESCC lesions are associated with distinct endoscopic features and a poorer prognosis than are non-PEESCC lesions.

Introduction: Particle radiotherapy (PRT) is a new option for the treatment of unresectable pancreatic cancer (PC). While gastrointestinal bleeding (GIB) is a feared adverse event, real-world evidence in this setting is limited.

Methods: We conducted a single-center retrospective study to evaluate the frequency and outcomes of GIB and to elucidate the risk factors for GIB after PRT for PC.

Results: Thirty-four patients were included. Twenty-nine received PRT to the pancreatic primary, while five received PRT for metastases. Concurrent chemotherapy was given to 26 patients (76%). Eleven patients (32%) experienced acute GIB symptoms after PRT. Median time from PRT to GIB was 13.2 months. Endoscopic signs of hemorrhage were observed in 8 patients (24%), and endoscopic hemostasis was performed in six (18%). Three cases presented with ruptured pseudoaneurysms, of which two were treated with transarterial embolization. Hemostasis was ultimately achieved in all cases, and no deaths occurred directly as a result of GIB. However, overall survival after GIB was short (median: 1.9 months). Median overall survival after PRT tended to be longer in bleeders than in non-bleeders (26.8 vs. 22.7 months, p = 0.03). Concurrent chemotherapy was associated with a lower risk of GIB in univariate analysis (p = 0.05).

Conclusion: GIB after PRT may not be as rare as previously believed, particularly in the terminal stages of PC.