Digestion最新文献

{"title":"Identifying Post-Surgical Recurrence Subtype of T1-Stage Colorectal Cancer by Machine Learning.","authors":"Xue Zhou, Kazutomo Togashi, Xin Zhu, Tuao Zhang, Yoshiki Kajiwara, Shiro Oka, Shinji Tanaka, Takahiro Nakamura, Manabu Takamatsu, Kinichi Hotta, Masayoshi Yamada, Hiroaki Ikematsu, Shinji Nagata, Kazutaka Yamada, Jun Konishi, Soichiro Ishihara, Yusuke Saitoh, Kenji Matsuda, Koji Komori, Megumi Ishiguro, Yuzuru Tamaru, Takashi Okuyama, Akihiro Ohuchi, Shinobu Ohnuma, Kazuhiro Sakamoto, Tamotsu Sugai, Yoichi Ajioka, Kenichi Sugihara, Hideki Ueno","doi":"10.1159/000550959","DOIUrl":"10.1159/000550959","url":null,"abstract":"<p><strong>Introduction: </strong>Traditional risk stratification heavily relies on expert judgment and manually established thresholds. This study aims to automatically identify subtypes in the patients of T1-stage colorectal cancer with distinct clinicopathologic characteristics and recurrence risk profiles, using machine learning.</p><p><strong>Methods: </strong>We analyzed data from 3,367 patients (mean follow-up, 1,281 days) with T1 colorectal cancer who underwent surgical resection between 2009 and 2016 across 27 high-volume core Japanese institutions. Patients were split into derivation and test datasets (4:1 ratio). Hierarchical clustering was employed to identify recurrence subtypes in the derivation dataset. Machine learning classifiers were developed and validated on the test dataset. Co-occurrence and Bayesian network analyses aided interpretation.</p><p><strong>Results: </strong>Three distinct subtypes were identified: two high-risk (subtypes 1 and 2) and one low-risk (subtype 3). Subtype 1 was predominantly associated with polypoid morphology (94.8%), whereas subtype 2 was characterized by flat morphology (89.4%). Subtype 2 showed a relatively consistent presence across most factors, with comparable levels of lymphatic invasion, vascular invasion, and tumor budding. Subtype 3 shared similarities with subtype 1 in polypoid morphology (76.5%) but differed in other factors. These findings showed similar trend on the test dataset. Subtype-specific risk factors included lymphovascular invasion and nodal metastasis in both high-risk subtypes, while rectal location was unique to subtype 1 and polypoid morphology and large size were specific to subtype 2.</p><p><strong>Conclusion: </strong>This machine learning approach identified three distinct recurrence subtypes of T1 colorectal cancer, each with unique characteristics and risk profiles, indicating the potential value of subtype-specific clinical strategies.</p>","PeriodicalId":11315,"journal":{"name":"Digestion","volume":" ","pages":"1-13"},"PeriodicalIF":3.6,"publicationDate":"2026-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146156374","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapeutic Efficacy of Risankizumab for Small-Intestinal Lesions in Crohn's Disease: A Retrospective Study Using Double-Balloon Endoscopy.","authors":"Takeshi Yamamura, Tsunaki Sawada, Eri Ishikawa, Keiko Maeda, Kentaro Murate, Kazuhiro Furukawa, Takashi Hirose, Tadashi Iida, Yasuyuki Mizutani, Kentaro Yamao, Yoji Ishizu, Takuya Ishikawa, Takashi Honda, Masanao Nakamura, Hiroki Kawashima","doi":"10.1159/000550396","DOIUrl":"10.1159/000550396","url":null,"abstract":"<p><strong>Introduction: </strong>Risankizumab (RZB), an IL-23p19 monoclonal antibody, has demonstrated clinical efficacy in Crohn's disease (CD), yet evidence regarding its effectiveness for deep small-intestinal lesions remains scarce. These lesions are often underdiagnosed due to limited accessibility and subtle clinical presentation.</p><p><strong>Methods: </strong>We retrospectively analyzed 32 patients with moderate-to-severe CD who underwent total small-intestinal evaluation by double-balloon endoscopy (DBE) both before and 8-14 months after RZB initiation in clinical practice. Endoscopic disease activity was assessed using the modified Simple Endoscopic Score for Crohn's Disease (mSES-CD). Clinical response (Crohn's Disease Activity Index [CDAI]), biomarker changes (C-reactive protein, leucine-rich alpha-2 glycoprotein), and endoscopic outcomes were evaluated.</p><p><strong>Results: </strong>Mean mSES-CD significantly decreased from 14.3 to 8.2 (p < 0.001), indicating substantial mucosal improvement, particularly in the jejunum and deep ileum. Endoscopic remission (mSES-CD <2) was achieved in 13.3% of patients. Clinical remission (CDAI <150) occurred in 80% at week 12 and was sustained in 56% at 1 year. Significant biomarker improvements were observed. No progression of strictures was seen during follow-up.</p><p><strong>Conclusion: </strong>This study confirms the therapeutic efficacy of RZB for deep small-intestinal involvement in CD based on comprehensive DBE assessment. The results support the clinical utility of RZB in patients with refractory small-intestinal lesions, highlighting its potential to maintain 1 year disease control when ongoing mucosal inflammation is a concern. These findings underscore the importance of deep enteroscopic evaluation to optimize therapeutic strategies.</p>","PeriodicalId":11315,"journal":{"name":"Digestion","volume":" ","pages":"1-9"},"PeriodicalIF":3.6,"publicationDate":"2026-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146149315","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Controversies in Computer-Assisted Detection in Colonoscopy.","authors":"Martin Putera, Frederick Hong Xiang Koh, James Weiquan Li","doi":"10.1159/000550268","DOIUrl":"10.1159/000550268","url":null,"abstract":"<p><strong>Background: </strong>Artificial intelligence (AI) applications in endoscopy, particularly computer-aided detection (CADe), have shown consistent benefit in randomized controlled trials (RCTs), with improvements in adenoma detection rate (ADR) and reductions in adenoma miss rate (AMR). Despite these findings, adoption of CADe in routine colonoscopy remains controversial, with international guidelines issuing divergent recommendations.</p><p><strong>Summary: </strong>Evidence from RCTs demonstrates that CADe increases ADR, predominantly through detection of diminutive adenomas, while its effect on advanced adenomas is limited. Real-world implementation studies show comparatively diminished benefits, likely explained by factors which are difficult to measure, such as the absence of Hawthorne effect in real-world practice, the quality of mucosal exposure and decision-making regarding diminutive polyps. Cost-effectiveness analyses generally favour CADe even with varying assumptions across healthcare systems, although these are based on the high degree of improvement in ADR seen in RCTs with CADe. Potential harms include increased polypectomy of non-neoplastic lesions, higher lifetime colonoscopy burden, and the risk of deskilling among endoscopists. Concerns remain about bridging the gap between trial efficacy and real-world effectiveness, optimizing surveillance intervals, and mitigating deskilling and human-AI interaction issues.</p><p><strong>Key messages: </strong>(1) CADe improves ADR in RCTs, but real-world effectiveness is inconsistent and often lacklustre. (2) Gains in ADR are largely derived from diminutive adenomas, and less with advanced adenomas, with uncertain impact on clinically significant outcomes such as colorectal cancer incidence and mortality. (3) Cost-effectiveness analyses are generally favourable, but dependent on assumptions about ADR improvement, CADe cost, and surveillance policies. (4) Deskilling and altered endoscopist behaviour represent important considerations that require further study. (5) Future integration of CADe with computer-aided diagnosis (CADx) and quality-assurance (CAQ) tools may maximize clinical benefit and cost-effectiveness, but evidence gaps must be addressed before widespread implementation.</p>","PeriodicalId":11315,"journal":{"name":"Digestion","volume":" ","pages":"1-14"},"PeriodicalIF":3.6,"publicationDate":"2026-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146124217","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Paratracheal Air Stripe Sign: A Useful Chest X-Ray Finding for Diagnosis in Patients with Esophageal Achalasia.","authors":"Naoto Ujiie, Yuto Muranami, Chiaki Sato, Yusuke Taniyama, Hiroshi Okamoto, Yohei Ozawa, Hirotaka Ishida, Ryohei Ando, Atsushi Kunimitsu, Michiaki Unno, Takashi Kamei","doi":"10.1159/000550861","DOIUrl":"10.1159/000550861","url":null,"abstract":"<p><strong>Introduction: </strong>Esophageal achalasia is a rare motility disorder, and esophagogastroduodenoscopy (EGD) alone has limited diagnostic accuracy, often leading to delayed diagnosis. High-resolution manometry remains the diagnostic gold standard, but its availability in primary care is limited. Therefore, more accessible diagnostic methods are needed. Given the widespread use of chest X-ray, we investigated whether it reveals distinctive features in achalasia patients.</p><p><strong>Methods: </strong>In this retrospective cohort study, 215 patients with esophageal achalasia treated between 2015 and 2024 were analyzed. Diagnostic yields of EGD, esophagography, and computed tomography (CT) were evaluated among patients who underwent these examinations in primary care facilities. Chest X-rays were systematically reviewed for paratracheal radiolucency, and a novel radiographic sign - the paratracheal air stripe sign (PASS) - was defined as a paratracheal radiolucent area with a minimum width of ≥5 mm and length of ≥20 mm. To assess specificity, an additional analysis was performed in 210 patients with esophageal cancer as a non-achalasia control cohort.</p><p><strong>Results: </strong>Diagnostic yields in primary care were 41.1% for EGD, 88.4% for esophagography, and 34.8% for CT. PASS was present in 67.0% of achalasia cases and more frequent in patients with type I achalasia, sigmoid-type morphology, and advanced esophageal dilation. Among patients undiagnosed by EGD, 63.9% exhibited PASS. In the non-achalasia control cohort, PASS was observed in 18.0% of cases, predominantly in patients with structural esophageal changes such as tortuosity or dilatation.</p><p><strong>Conclusion: </strong>PASS represents a novel and clinically useful chest X-ray feature associated with esophageal achalasia. Its relatively high prevalence, even among cases missed by EGD, and low occurrence in non-achalasia patients suggest that routine assessment of PASS in chest X-rays may aid early detection and timely referral for definitive diagnosis, particularly in primary care settings.</p>","PeriodicalId":11315,"journal":{"name":"Digestion","volume":" ","pages":"1-10"},"PeriodicalIF":3.4,"publicationDate":"2026-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13008391/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146124196","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Electroacupuncture-Regulated Bile Acid Metabolism and Farnesoid X Receptor Expression in Constipation-Predominant Irritable Bowel Syndrome Rat: A Preclinical Study.","authors":"ShiYuan Jiang, XiaoYu Wang, ZhengYang Qu, Jing Guo, XiaoYu Liu, YangShuai Su, XiangHong Jing, JianHua Sun, LiXia Pei","doi":"10.1159/000550560","DOIUrl":"10.1159/000550560","url":null,"abstract":"<p><strong>Introduction: </strong>The efficacy of electroacupuncture (EA) treatment in alleviating visceral hypersensitivity with irritable bowel syndrome (IBS) has been established. Abnormal bile acid metabolism and farnesoid X receptor (FXR) expression are recognized as potential contributors to visceral hypersensitivity in IBS. This study as a preclinical study of IBS visceral hypersensitivity explored the potential of EA to reduce visceral hypersensitivity in rats with IBS by improving bile acid metabolism and FXR expression.</p><p><strong>Methods: </strong>Heterotypic intermittent stress (HIS) for 9 days was used to induce visceral hypersensitivity in constipation-predominant irritable bowel syndrome (IBS-C). EA/sham EA bilateral ST36 and LR3 acupoints began on the 5th day of HIS. Electromyography of the abdominal external oblique muscle and calcitonin gene-related peptide were used to assess colonic hypersensitivity. Colonoscopy and histopathological examination were used to evaluate pathological changes in the colon. Bile acid composition was analyzed using high-performance liquid chromatography-mass spectrometry, while FXR expression in colon tissue was quantified through immunofluorescence and Western blot.</p><p><strong>Results: </strong>HIS induced visceral hypersensitivity in IBS-C rats. EA not only regulated bile acid levels in the feces of IBS-C rats, but also had a downregulatory effect on the overexpression of FXR in the colon tissue of rats with IBS-C. The therapeutic effects were better than those of the sham EA. EA treatment alleviated visceral hypersensitivity in the colon of IBS-C rats.</p><p><strong>Conclusion: </strong>Our data suggested that EA normalized colonic bile acid signaling and FXR protein expression in an IBS-C rat model, offering a mechanistic hypothesis for future clinical evaluation.</p>","PeriodicalId":11315,"journal":{"name":"Digestion","volume":" ","pages":"1-14"},"PeriodicalIF":3.6,"publicationDate":"2026-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146124240","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association between the Gut Microbiota and the Pathophysiology of Irritable Bowel Syndrome: A Narrative Review.","authors":"Akira Andoh, Hiroto Miwa","doi":"10.1159/000550907","DOIUrl":"10.1159/000550907","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Summary: </strong>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.</p><p><strong>Key message: </strong>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.</p>","PeriodicalId":11315,"journal":{"name":"Digestion","volume":" ","pages":"1-10"},"PeriodicalIF":3.6,"publicationDate":"2026-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146124259","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"What Is the Optimal Endoscopic Resection Method for Intermediate-Sized (10-20 mm) Superficial Non-Ampullary Duodenal Epithelial Tumors? A Systematic Review.","authors":"Yasushi Yamasaki, Hiroyoshi Iwagami, Katsunori Matsueda, Kohei Takizawa, Koichi Kurahara, Naomi Kakushima, Nobutsugu Abe, Osamu Dohi, Satoru Nonaka, Seiichiro Fukuhara, Shoichi Yoshimizu, Takashi Hirose, Shu Hoteya, Ryoji Kushima, Motohiko Kato, Naohisa Yahagi","doi":"10.1159/000550811","DOIUrl":"10.1159/000550811","url":null,"abstract":"<p><strong>Introduction: </strong>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.</p><p><strong>Methods: </strong>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 lesions 10-20 mm in size and 11 single-center lesions less than 20 mm), including en bloc and R0 resection rates, delayed bleeding, intraoperative and delayed perforations, and recurrence.</p><p><strong>Results: </strong>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 perforations 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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":11315,"journal":{"name":"Digestion","volume":" ","pages":"1-9"},"PeriodicalIF":3.6,"publicationDate":"2026-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146092383","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Newly Developed Evaluation of Esophageal Wall Motion Using Endoscopic Ultrasonography via Transnasal Endoscopy: Clinical Application in Esophageal Achalasia.","authors":"Emiko Bukeo, Noriaki Manabe, Takako Etani, Maki Ayaki, Minoru Fujita, Ken Haruma","doi":"10.1159/000550665","DOIUrl":"10.1159/000550665","url":null,"abstract":"<p><strong>Introduction: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":11315,"journal":{"name":"Digestion","volume":" ","pages":"1-10"},"PeriodicalIF":3.6,"publicationDate":"2026-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146060857","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of LGR5 and TFF2 as Biomarkers in High-Risk Chronic Atrophic Gastritis: From Multi-Omics Mining to Clinical Validation.","authors":"Qingqing Zhang, Di Wu, Fengyun Guo, Shengnan Yang, Lijing Bao, Ruiying Zhang, Ping Wang","doi":"10.1159/000549887","DOIUrl":"10.1159/000549887","url":null,"abstract":"<p><strong>Introduction: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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).</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":11315,"journal":{"name":"Digestion","volume":" ","pages":"1-19"},"PeriodicalIF":3.4,"publicationDate":"2026-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13421305/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146043995","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<italic>Helicobacter pylori</italic>-Naïve Gastric Neoplasms: Clinicopathological and Molecular Features and Diagnostic Challenges.","authors":"Kotaro Shibagaki, Satoshi Kotani, Yusuke Takahashi, Shinsuke Suemitsu, Mamiko Nagase, Asuka Araki, Shigeru Kawabata, Daisuke Niino, Norihisa Ishimura, Shunji Ishihara","doi":"10.1159/000550663","DOIUrl":"10.1159/000550663","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Summary: </strong>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.</p><p><strong>Key messages: </strong>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.</p>","PeriodicalId":11315,"journal":{"name":"Digestion","volume":" ","pages":"1-17"},"PeriodicalIF":3.4,"publicationDate":"2026-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13012773/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146044024","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}