Digestion[JOURNAL]
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200 papers
IL-22 Associates with Venous Thromboembolism in Inflammatory Bowel Disease: A Hypothesis-Generating Study.
Cola R, Rogler G, Biedermann L … +3 more , Murray F, Krapf R, Beer JH
Digestion · 2026 Apr · PMID 42044078 · Full text
INTRODUCTION: Patients with inflammatory bowel disease (IBD) are at significantly increased risk for venous thromboembolism (VTE). We hypothesized that (i) the increased risk is associated with elevated levels of typical...
INTRODUCTION: Patients with inflammatory bowel disease (IBD) are at significantly increased risk for venous thromboembolism (VTE). We hypothesized that (i) the increased risk is associated with elevated levels of typical pro-inflammatory cytokines and (ii) that elevated concentrations of specific cytokines could possibly predict a thromboembolic event. METHODS: We examined 226 well-characterized patients of the Swiss IBD cohort study (SIBDCS); we analyzed serum samples from IBD patients with documented VTE (n = 78) and compared them 2:1 with age- and sex-matched controls without VTE of the same cohort (n = 148). An array of 12 typical proinflammatory cytokines (IL2, IL17a, IL12p70, IL8, IL1b, IL4, IL5, IFN-γ, IL6, IL22, TNF-α, and IL-10) was quantified. Detailed disease characteristics - such as activity (mild, moderate, and quiescent) as well as age at visit, sex, and the time interval between thrombosis and blood collection were statistically analyzed. RESULTS: IL2, IL17a, IL12p70, IL8, IL1b, IL4, IL5, IFN-γ, IL6, TNF-α, and IL-10 showed no statistical difference between the thrombosis and control group. In contrast, IL-22 levels (0.709 vs. 0.542 pg/mL, p < 0.05) were significantly higher in the VTE group. CONCLUSIONS: IL-22, may associate with an increased risk of VTE in IBD in this hypothesis-generating study, whereas the other inflammatory parameters measured were not associated. This marker appears to be independent of disease activity, as the other cytokines, which are considered markers of disease activity, did not show a significant difference in comparison. Further targeted and serial measurements will have to confirm our findings.
Esophageal Hyposensitivity: A Key Link to Aspiration Pneumonia in Patients with Achalasia.
Inamura K, Wada M, Ihara E … +10 more , Hata Y, Tsuru H, Fukuya H, Esaki M, Minoda Y, Bai X, Tanaka Y, Chinen T, Ogino H, Ogawa Y
Digestion · 2026 Apr · PMID 42030216 · Publisher ↗
INTRODUCTION: Aspiration pneumonia (AP) is a serious complication of achalasia; however, its risk factors and mechanisms remain unclear. We aimed to identify the clinical characteristics associated with AP and explore it...
INTRODUCTION: Aspiration pneumonia (AP) is a serious complication of achalasia; however, its risk factors and mechanisms remain unclear. We aimed to identify the clinical characteristics associated with AP and explore its underlying pathophysiology. METHODS: This retrospective single-center study included 70 patients diagnosed with achalasia using high-resolution manometry (HRM) between 2016 and 2022. Patients were categorized into non-AP (n = 42) and AP (n = 28) groups based on chest computed tomography findings. Clinical symptoms (Eckardt score), esophagographic findings, and HRM parameters were compared. Propensity score matching (PSM) was performed to adjust for age and disease duration. In a matched sub-cohort, esophageal mucosal biopsies were analyzed using quantitative real-time PCR to compare mechanosensory/chemosensory channels and inflammatory cytokines. RESULTS: Patients with AP were older and tended to have a longer disease duration than those without AP. The Eckardt score was significantly lower in the AP group, despite no differences in HRM-defined or morphological subtypes on contrast esophagography. This difference remained significant after PSM. Expression levels of TRPV1, TRPV4, and PIEZO1 were significantly reduced in the achalasia (comprising both non-AP and AP patients) group compared with controls and were further decreased in the AP group compared with the non-AP group. Cytokine levels did not differ between the non-AP and AP groups. CONCLUSION: Esophageal hyposensitivity is a key risk factor for AP in achalasia, independent of HRM-defined or morphological subtypes. Downregulation of TRPV1, TRPV4, and PIEZO1 may underlie reduced symptom perception, providing novel insights into the pathophysiology of aspiration in achalasia.
Sequential Janus Kinase Inhibitor Switching in Ulcerative Colitis Patients Maintaining Remission: A Multicenter Experience.
Uchida G, Sawada T, Nakamura M … +6 more , Yamamura T, Maeda K, Ishikawa E, Murate K, Tsuzuki T, Kawashima H
Digestion · 2026 Apr · PMID 42013013 · Publisher ↗
INTRODUCTION: Given the safety concerns associated with the long-term use of Janus kinase (JAK) inhibitors, establishing effective "exit strategies" is crucial for patients with ulcerative colitis (UC). This study invest...
INTRODUCTION: Given the safety concerns associated with the long-term use of Janus kinase (JAK) inhibitors, establishing effective "exit strategies" is crucial for patients with ulcerative colitis (UC). This study investigated the efficacy and safety of switching from tofacitinib (TOF) or upadacitinib (UPA) to the JAK1-selective filgotinib (FIL) in patients maintaining remission. METHODS: We conducted a retrospective, multicenter study involving 13 UC patients who achieved clinical remission with TOF or UPA and subsequently switched to FIL. The primary endpoint was the cumulative non-relapse rate. RESULTS: During a median follow-up of 679 days, symptomatic relapse occurred in 53.8% (7/13) of patients. The 1-year cumulative non-relapse rate was 71.4% for the TOF-switch group and 31.3% for the UPA-switch group. However, many relapses were successfully managed through temporary treatment adjustments, including FIL dose escalation or topical therapy. No serious adverse events were recorded. CONCLUSION: Sequential switching to FIL may represent a practical intermediate maintenance strategy before complete drug withdrawal, balancing disease control with potential safety benefits.
Potassium-Competitive Acid Blocker Increases Ileal Permeability and Exacerbates Ileal Inflammation under Stress Conditions in a Mouse Model of Eosinophilic Enteritis.
Yamamoto K, Tanaka F, Nishida Y … +7 more , Maruyama H, Ominami M, Nadatani Y, Otani K, Fukunaga S, Hosomi S, Fujiwara Y
Digestion · 2026 Apr · PMID 42008374 · Publisher ↗
INTRODUCTION: Potassium-competitive acid blockers (P-CABs) have been empirically administered to treat non-esophageal eosinophilic gastrointestinal diseases, although their efficacy remains unproven. Our previous finding...
INTRODUCTION: Potassium-competitive acid blockers (P-CABs) have been empirically administered to treat non-esophageal eosinophilic gastrointestinal diseases, although their efficacy remains unproven. Our previous findings demonstrated that psychological stress impairs the intestinal barrier and exacerbates eosinophilic enteritis (EoN) in a mouse model. Moreover, we demonstrated that P-CAB increased intestinal permeability under psychological stress. The aim of this study was to clarify the hypothesis that P-CAB exacerbate EoN by increasing intestinal permeability under stressful conditions. METHODS: An EoN model was established in BALB/c mice using ovalbumin (OVA) sensitization and challenge. Mice were subjected to water avoidance stress (WAS) or sham stress (SS) and were administered P-CAB or saline as a vehicle. The ileum was collected for the analysis of ileal microscopic inflammation, mRNA and protein expression levels of T helper type 2 (Th2) cytokines, and ex vivo ileal permeability using a Ussing chamber. RESULTS: Compared with the WAS + vehicle group, WAS + P-CAB significantly exacerbated the incidence of diarrhea, villus/crypt ratio, eosinophil and mast cell counts, mRNA and protein levels of Th2 cytokines, OVA-specific immunoglobulin E protein levels, and ileal permeability. Larazotide acetate, a zonulin inhibitor, significantly improved ileal inflammation and decreased ileal permeability in the WAS + P-CAB-treated EoN mice. CONCLUSIONS: P-CAB increased ileal permeability and exacerbated EoN under stressful conditions. Furthermore, a zonulin inhibitor demonstrated therapeutic effects in EoN with P-CAB under stressful conditions.
Association of Equol Production Status with the Presence of Precancerous Colorectal Lesions in Japan.
Kaneta Y, Yamaji T, Harada K … +10 more , Fujitani T, Lyu Z, Sassa MH, Ikematsu H, Hotta K, Sekiguchi M, Kakugawa Y, Kobayashi N, Matsuda T, Iwasaki M
Digestion · 2026 Apr · PMID 42008366 · Publisher ↗
INTRODUCTION: Epidemiological evidence regarding the association between equol and precancerous colorectal lesions, including adenomas, sessile serrated lesions, and traditional serrated adenomas, remains unclear. Moreov...
INTRODUCTION: Epidemiological evidence regarding the association between equol and precancerous colorectal lesions, including adenomas, sessile serrated lesions, and traditional serrated adenomas, remains unclear. Moreover, since equol production status depends on the composition of the gut microbiota and varies widely among individuals, evaluation based on plasma levels is essential. In this study, we evaluated the association between plasma equol levels and precancerous colorectal lesions. METHODS: This cross-sectional study included residents aged 40-79 years in Izu Oshima, Japan. Blood samples were collected at study registration prior to colonoscopy under fasting conditions. In 2024, plasma equol levels were analyzed by gas chromatography-mass spectrometry, and individuals above the measurement quantification limit were classified as equol producers. Colonoscopy was performed for screening, and lesions were assessed based on endoscopic and pathological findings. Odds ratios (ORs) and their 95% confidence intervals (CIs) for precancerous lesions were calculated. RESULTS: Of the 993 participants analyzed, 509 had precancerous colorectal lesions, while 484 served as controls. No significant association was observed between equol production status and the presence of precancerous colorectal lesions (OR: 1.04, 95% CI: 0.77-1.40). Although not statistically significant, an inverse trend was suggested in advanced lesions, defined as advanced adenomas or sessile serrated lesions with dysplasia (OR: 0.63, 95% CI: 0.34-1.18). CONCLUSION: This study did not provide significant evidence of an association between equol production status and the presence of precancerous colorectal lesions. Future prospective cohort studies and detailed analysis of intestinal microbiota are needed to clarify the effects of equol on colorectal carcinogenesis.
Autoantibodies Are Useful in Monitoring Disease Activity and Predicting Relapses in Autoimmune Pancreatitis.
Falk L, Murillo K, Ebert MP … +2 more , Schneider A, Hirth M
Digestion · 2026 Apr · PMID 41961744 · Publisher ↗
INTRODUCTION: Autoimmune pancreatitis (AiP) is an inflammatory disease typically treated with corticosteroids. But repeated corticosteroid treatment (CST) can cause significant side effects, raising the need for better m...
INTRODUCTION: Autoimmune pancreatitis (AiP) is an inflammatory disease typically treated with corticosteroids. But repeated corticosteroid treatment (CST) can cause significant side effects, raising the need for better management strategies. This study investigated the role of "conventional" autoantibodies in monitoring disease activity and progression in AiP to establish individualized treatment strategies. METHODS: The study examined 55 AiP patients from the University Medical Centre Mannheim (Germany) and aimed to correlate "conventional" autoantibodies with disease severity, relapse risk, and other clinical parameters by analyzing 769 treatment appointments. RESULTS: A total of 56% of AiP patients have elevated levels of "conventional" autoantibodies, particularly smooth muscle antibody, anti-neutrophil cytoplasmic antibodies (ANCA), and rheumatoid factor. Rheumatoid factor was especially elevated in AiP type 1, whereas ANCA was elevated in AiP type 2. Increased disease activity is assumed in case of high AiP activity score, before (vs. after) CST, in the case of emergency (vs. elective) treatment, and in the presence of other organ involvement. Autoantibodies were found to correlate with these clinical markers of disease activity. Furthermore, symptomatic inflammatory bowel disease in AiP type 2 was associated with increased ANCA titers. The presence of a focal mass was especially associated with an increase in rheumatoid factor. Notably, patients with elevated autoantibodies at baseline and particularly those with insufficient reduction of autoantibody titers after CST had a higher likelihood of relapse. CONCLUSION: While conventional autoantibodies are not diagnostic for AiP, they are useful in monitoring disease activity and predicting relapse. Testing for autoantibodies could help guide individual treatment decisions.
Diagnosis of Eosinophilic Enteritis Using Double Balloon Enteroscopy-Guided Multisite Biopsies.
Yamashina T, Shimatani M, Nakagawa T … +12 more , Takayama T, Toyonaga H, Sano Y, Orino M, Matsumoto H, Saito N, Sumimoto K, Takeo M, Fukata N, Yoshida K, Naganuma M, Yamada Y
Digestion · 2026 Mar · PMID 41875295 · Publisher ↗
INTRODUCTION: Eosinophilic enteritis (EoN) remains underrecognized because of nonspecific symptoms and difficulty obtaining deep small intestinal biopsies. We evaluated the diagnostic utility of double balloon enteroscop...
INTRODUCTION: Eosinophilic enteritis (EoN) remains underrecognized because of nonspecific symptoms and difficulty obtaining deep small intestinal biopsies. We evaluated the diagnostic utility of double balloon enteroscopy (DBE)-guided multisite biopsy and explored tissue and blood eosinophil thresholds distinguishing EoN from non-EoN conditions. METHODS: This single-center retrospective cohort included consecutive patients who underwent DBE with small intestinal biopsies (January 2021-December 2024). Biopsies were obtained from up to six predefined segments (duodenum, upper/lower jejunum, upper/lower ileum, terminal ileum). EoN diagnosis required abdominal pain and/or diarrhea, exclusion of competing diagnoses, and small intestinal biopsy-proven eosinophilic infiltration. Peripheral eosinophil percentage and computed tomography (CT) findings were recorded. The primary outcome was the extent of small intestinal eosinophil infiltration in patients with EoN. Secondary outcomes were the peripheral blood eosinophil count, clinical background, and exploratory comparisons with non-EoN cases. RESULTS: Eighteen patients were included (5 EoN, 13 non-EoN). CT showed small intestinal wall edema in 3 patients with EoN. Peripheral eosinophil proportion was significantly higher in EoN (median, 15.2% vs. 1.9%; p < 0.01). Across 83 biopsy specimens (25 EoN, 58 non-EoN), patient-level peak eosinophil counts were greater in EoN (median, 77/HPF [22-213] vs. 23/HPF [12-111]; p < 0.001). All patients with EoN had at least one segment with ≥50 eosinophils per high-power field, while two with non-EoN reached this threshold. No DBE-related serious adverse events occurred. CONCLUSION: EoN exhibits significantly greater eosinophil infiltration than non-EoN. DBE-guided multisite biopsy enables accurate recognition of EoN. Prospective multicenter studies are needed to refine site-specific thresholds and standardize HPF reporting.
<italic>Bifidobacterium bifidum</italic> G9-1 and Quality of Life in Chronic Constipation: A Multicenter, Double-Blind, Randomized Controlled Trial.
Misawa N, Kessoku T, Inoue K … +13 more , Suzuki H, Tamura S, Takatsu T, Yoshihara T, Ashikari K, Kato T, Fuyuki A, Kato S, Ohkubo H, Higurashi T, Yoneda M, Kurihashi T, Nakajima A
Digestion · 2026 Mar · PMID 41843723 · Full text
INTRODUCTION: Patients with constipation often experience impaired quality of life (QOL). A previous open-label study of Bifidobacterium bifidum G9-1 (BBG9-1) in patients with chronic constipation reported a significant...
INTRODUCTION: Patients with constipation often experience impaired quality of life (QOL). A previous open-label study of Bifidobacterium bifidum G9-1 (BBG9-1) in patients with chronic constipation reported a significant improvement in defecation-related QOL. Thus, we conducted a multicenter, randomized controlled study to assess the efficacy of BBG9-1 in patients with chronic constipation. METHODS: Patients diagnosed with or being treated for chronic constipation between July 2020 and January 2022 and having an overall score of ≥1 on the Japanese version of the patient assessment of constipation quality of life scale (JPAC-QOL) were included. Following a 2-week baseline period, BBG9-1 or placebo was administered for 8 consecutive weeks. The primary endpoint was the change in the JPAC-QOL overall score pre-administration and 8 weeks post-administration of BBG9-1; secondary endpoints were changes in JPAC-QOL subscale scores, number of days of defecation, stool consistency, straining during defecation, and feeling of incomplete evacuation after defecation pre-administration and 8 weeks post-administration. RESULTS: Data from 140 patients (83 women) were analyzed. The JPAC-QOL overall score improved by 0.65 ± 0.56 in the treatment group and 0.54 ± 0.67 in the placebo group, with no significant difference (p = 0.282). However, the physical discomfort subscale showed a nominally significant improvement in the treatment group (p = 0.041). Stratified analysis revealed increased defecation frequency and reduced straining in those with high baseline straining scores. No adverse events were reported. CONCLUSION: BBG9-1 administration reduced physical discomfort but did not significantly improve the JPAC-QOL overall score, indicating its limited effect on chronic constipation.
Beyond <italic>Helicobacter pylori</italic>: Current Insights into <italic>H. pylori</italic>-Naive Gastric Cancer.
Woo SWD, Yeap VSX, Hau VSF … +6 more , Tan YB, Lau LHS, Yip HC, Lui R, Chan SM, Chiu P
Digestion · 2026 Mar · PMID 41838833 · Full text
BACKGROUND: The increasing global incidence of Helicobacter pylori-naive gastric cancer (HPnGC) has established it as a clinical entity warranting further study of its diagnosis, pathogenesis, aetiologies, classification...
BACKGROUND: The increasing global incidence of Helicobacter pylori-naive gastric cancer (HPnGC) has established it as a clinical entity warranting further study of its diagnosis, pathogenesis, aetiologies, classifications, and management. SUMMARY: HPnGC is an emerging and distinct clinical entity, with its relative burden increasing as global efforts for H. pylori eradication succeeds. The cancer is linked to specific aetiologies such as Epstein-Barr virus, autoimmune gastritis, and certain hereditary cancer predisposition syndromes, and is also linked to more aggressive histological subtypes, unfavourable anatomical locations, advanced stages at diagnosis, and potentially carries a poorer prognosis compared to its H. pylori-positive counterpart. Diagnosis requires stringent multi-modal confirmation of absent infection. Currently, endoscopic, surgical, and systemic treatments are similar to those for H. pylori-positive gastric cancer. KEY MESSAGES: This review demonstrates wide knowledge gaps and areas requiring further clarification. Accurate diagnosis remains challenging due to the absence of standardized criteria, highlighting the need for a robust diagnostic framework. Furthermore, it is imperative for further research into the different molecular subtypes and carcinogenic mechanisms to identify cost-effective surveillance methods and effective treatment strategies that contribute to the development of a comprehensive and practical clinical guideline.
Short- and Long-Term Outcomes of Mirikizumab for Ulcerative Colitis: A Real-World Multicenter Retrospective Cohort Study from the INSIGHT Study.
Sawada T, Yamamura T, Maeda K … +15 more , Ishikawa E, Murate K, Miyake N, Matsuura R, Fujiyoshi T, Uchida G, Suzuki H, Nishikawa T, Kuno T, Hattori S, Urata N, Ohashi A, Hasegawa I, Nakamura M, Kawashima H
Digestion · 2026 Mar · PMID 41824618 · Publisher ↗
INTRODUCTION: Mirikizumab (MIR), a selective IL-23p19 inhibitor, has shown efficacy in clinical trials for ulcerative colitis (UC). However, real-world data, especially on long-term outcomes and in treatment-experienced...
INTRODUCTION: Mirikizumab (MIR), a selective IL-23p19 inhibitor, has shown efficacy in clinical trials for ulcerative colitis (UC). However, real-world data, especially on long-term outcomes and in treatment-experienced populations, remain limited. METHODS: We conducted a multicenter retrospective cohort study involving 85 patients with moderate-to-severe UC who initiated MIR between July 2023 and December 2024 across 12 Japanese centers. Co-primary endpoints were clinical remission (Simple Clinical Colitis Activity Index [SCCAI] ≤2 and with no rectal bleeding) at weeks 12 and 52. Secondary outcomes included corticosteroid (CS)-free remission, C-reactive protein normalization, treatment persistence, and safety. RESULTS: Clinical remission was achieved in 62.4% at week 12 and 55.3% at week 52. CS-free remission rates were identical to overall remission at both time points. MIR maintained effectiveness regardless of prior exposure to biologics or JAK inhibitors. Early clinical response at week 4 independently predicted week 52 remission, while steroid dependence was a predictor at week 12. Among patients receiving extended induction, 27.3% of initial nonresponders achieved remission by week 24. Treatment was generally well tolerated, with 17.6% experiencing adverse events and 9.4% discontinuing due to these events. No serious infections or hospitalizations occurred. CONCLUSION: MIR demonstrated durable effectiveness and a favorable safety profile over 52 weeks in a real-world UC population, including those with prior treatment failures. These findings support MIR as a viable long-term therapeutic option in routine clinical practice.
Involvement of Gastrointestinal Functional Disorder in the Management of Inflammatory Bowel Disease.
Arai R, Fukata M
Digestion · 2026 Mar · PMID 41802112 · Publisher ↗
BACKGROUND: Recent therapeutic advances have yielded higher remission rates than before in patients with inflammatory bowel disease (IBD), while many patients in remission still experience gastrointestinal symptoms. Thes...
BACKGROUND: Recent therapeutic advances have yielded higher remission rates than before in patients with inflammatory bowel disease (IBD), while many patients in remission still experience gastrointestinal symptoms. These persistent symptoms could be caused by functional bowel disorders and are associated with increased psychological distress. SUMMARY: Patients with IBD may have symptoms like functional gastrointestinal disorders (FGID) even before the disease onset, and distinguishing between disease flare and functional symptoms is often difficult. Gastrointestinal infections such as Campylobacter infection may contribute to the onset of both IBD and FGID. The pathophysiology of FGIDs in IBD is complex and multifactorial, involving genetic predisposition, dysregulation of the gut-brain axis, intestinal dysbiosis, impaired mucosal permeability, and low-grade inflammation. These factors further interact with each other to cause symptoms. KEY MESSAGES: Management of patients with IBD who present symptoms of FGIDs requires a multifaceted approach based on the principles of FGID treatment under the premise of complete control of intestinal inflammation. In this review, we discuss the clinical overlap, pathophysiology, diagnostic challenges, and a structured approach for patients with IBD who are complicated by symptoms of FGIDs.
Diagnosis of Functional Dyspepsia and Novel Gastrointestinal Functional Assessments.
Takeda T, Hojo M, Nagahara A
Digestion · 2026 Mar · PMID 41790580 · Full text
BACKGROUND: Functional dyspepsia (FD) is a common disorder of gut-brain interaction characterized by postprandial distress and epigastric pain, which significantly impairs quality of life and increases healthcare burden....
BACKGROUND: Functional dyspepsia (FD) is a common disorder of gut-brain interaction characterized by postprandial distress and epigastric pain, which significantly impairs quality of life and increases healthcare burden. Although the Rome IV criteria and Japanese guidelines have refined its definition, the pathophysiology remains multifactorial, involving gastric motility abnormalities, visceral hypersensitivity, and autonomic dysfunction. Traditional diagnostic approaches, mainly based on clinical history and exclusion of organic diseases, are limited in elucidating the underlying mechanisms. SUMMARY: Recent advances in gastrointestinal functional assessments have enabled more detailed evaluation of gastric accommodation, emptying, motility, and sensory function. Techniques such as barostat, antroduodenal manometry, gastric scintigraphy, and gastric emptying breath tests have been established in research settings, while newer modalities - including cine magnetic resonance imaging, body surface gastric mapping (BSGM), and wireless motility capsule (WMC) - offer noninvasive and comprehensive insights into gastric motor and sensory function. Furthermore, the use of endoscopy-based functional testing has expanded diagnostic capabilities. Autonomic nervous system testing, including heart rate variability analysis and exploratory wearable device approaches, provides additional perspectives on the gut-brain axis. Collectively, these tools have advanced the understanding of FD pathophysiology; nonetheless, their availability and standardization remain limited. KEY MESSAGES: FD is highly prevalent and burdensome, with a complex and multifactorial pathophysiology. A wide range of gastrointestinal functional tests has been developed from established barostat and scintigraphy to emerging noninvasive methods such as cine magnetic resonance imaging, endoscopy-based functional testing, WMC, and BSGM. These novel approaches can capture both motor and sensory abnormalities, offering new opportunities for personalized management of FD. Standardization, validation, and wider clinical implementation of these functional assessments are needed to translate research advances into routine practice.
Therapeutic Potential of the Low-Fermentable Oligosaccharides, Disaccharides, Monosaccharides, and Polyols Diet in Functional Dyspepsia: A Systematic Review.
Katsumata R, Shinozaki S, Oshima T … +16 more , Watanabe J, Asakawa A, Kamiya T, Kessoku T, Suzuki H, Nakamura K, Hojo M, Mihara H, Mori H, Yamamoto T, Tanaka F, Futagami S, Haruma K, Joh T, Kusano M, Yakabi K
Digestion · 2026 Mar · PMID 41774601 · Publisher ↗
INTRODUCTION: Dietary factors, including fermentable oligo-, di-, monosaccharides, and polyols (FODMAPs), have been implicated in symptom generation among patients with functional dyspepsia (FD). Accordingly, a low-FODMA...
INTRODUCTION: Dietary factors, including fermentable oligo-, di-, monosaccharides, and polyols (FODMAPs), have been implicated in symptom generation among patients with functional dyspepsia (FD). Accordingly, a low-FODMAP diet (LFD) has been proposed as a potential therapeutic approach. However, no systematic review has yet been conducted. This study aimed to evaluate the effects of an LFD on gastrointestinal symptoms and quality of life (QoL) in patients with FD. METHODS: Following PRISMA guidelines, Medline, Embase, and Central were searched through October 2025. Studies involving adults or children diagnosed with FD and treated with a structured LFD or lower habitual FODMAP intervention were included. Randomized controlled trials (RCTs) and non-RCTs were assessed for methodological quality using the Cochrane RoB 2 tool and the Newcastle-Ottawa Scale, respectively. RESULTS: Ten studies involving 4,329 patients (two RCTs and eight non-RCTs) met the inclusion criteria. Both RCTs demonstrated significant improvements in dyspeptic symptoms and QoL following an LFD compared with the control or baseline. Non-RCTs consistently showed symptom relief and improved QoL in adults and children under dietitian supervision, whereas lower habitual FODMAP intake was associated with a higher risk of FD prevalence in cross-sectional studies. Overall, the studies exhibited a predominantly moderate risk of bias. CONCLUSION: Current evidence suggests that an LFD may alleviate gastrointestinal symptoms and enhance QoL in patients with FD. However, existing studies remain few and heterogeneous. High-quality, adequately powered clinical and mechanistic studies are warranted to confirm its therapeutic efficacy and clarify the underlying physiological mechanisms.
Positive Margins and Lymphovascular Invasion Represent Risk Factors for Remnant Tumor or Late Recurrence in Endoscopic or Local Resection of Duodenal Neuroendocrine Tumors.
Kim I, Cho YK, Choi IH … +2 more , Kang D, Park JM
Digestion · 2026 Feb · PMID 41762683 · Publisher ↗
INTRODUCTION: Duodenal neuroendocrine tumors (DNETs) are rare neoplasms with malignant potential, and the optimal strategy between endoscopic resection (ER) and surgical resection (SR) remains debated. This study evaluat...
INTRODUCTION: Duodenal neuroendocrine tumors (DNETs) are rare neoplasms with malignant potential, and the optimal strategy between endoscopic resection (ER) and surgical resection (SR) remains debated. This study evaluated the clinical outcomes of ER and SR in patients with DNETs at a single tertiary center. METHODS: We retrospectively reviewed patients diagnosed with DNETs at Seoul St. Mary's Hospital between 2009 and 2025. The clinical features, treatment modalities, pathology, complications, and long-term outcomes were analyzed. Median follow-up was 4.76 years (0.03-13.70). RESULTS: Sixty-five patients were included (mean age, 62.9 years; 31 men). Fifty patients underwent ER (26 EMR, 9 EMR-L, 11 EMR-P, 1 ESD, 2 ampullectomy, and 1 removal with hot biopsy), while 15 underwent SR (10 wedge resections and 5 pancreatoduodenectomy/Whipple). The en bloc resection rate for ER was 93.9% (46/49), with a histopathologically curative resection rate of 69.4%. Fourteen ER patients had positive margins; one underwent additional surgery with a confirmed residual tumor, but the others showed no recurrence during a median follow-up of 6.8 years. Perforation occurred in three ER cases (6%), all of whom were successfully treated. Among the wedge resections, R1 resection occurred in 3/10 cases. One patient developed lymph node recurrence 12 years after wedge resection, whereas the others remained disease-free. Overall, recurrence was rare in both groups. CONCLUSION: ER and surgical local resection are effective, minimally invasive treatments for small DNETs, with high resection rates and acceptable safety. However, positive margins and lymphovascular invasion are risk factors for remnant tumors or late recurrence, underscoring the importance of long-term surveillance in high-risk patients.
A Comprehensive Literature-Based Analysis of Prognosis in Patients with Cronkhite-Canada Syndrome.
Imazu Y, Ono M, Takeda Y … +7 more , Ishii M, Matsuoka N, Nakajima H, Toyoda A, Takahara Y, Harada H, Ogata Y
Digestion · 2026 Feb · PMID 41762677 · Publisher ↗
INTRODUCTION: Cronkhite-Canada syndrome (CCS) is a rare, nonhereditary gastrointestinal disorder with unclear etiology and limited treatment consensus. Given the scarcity of data, we aimed to construct a pooled literatur...
INTRODUCTION: Cronkhite-Canada syndrome (CCS) is a rare, nonhereditary gastrointestinal disorder with unclear etiology and limited treatment consensus. Given the scarcity of data, we aimed to construct a pooled literature-based cohort to analyze survival outcomes and identify prognostic factors to inform future therapeutic strategies. METHODS: We developed a literature-based cohort of CCS by extracting individual patient data from published case reports and two in-house cases. Articles were selected through a systematic screening process based on relevance and data availability. Information collected included age, sex, clinical symptoms, laboratory findings, endoscopic and histological features, treatment approaches, and outcomes. The compiled dataset was used to explore clinical characteristics, treatment patterns, and survival trends across reported cases. RESULTS: A total of 200 CCS patients were analyzed, including 198 from literature and 2 in-house cases. Most patients presented with diarrhea, weight loss, skin pigmentation, and alopecia. Polyps were commonly found in the stomach and colon. Survival analysis showed a 1-year survival rate of 92.3% and a 3-year survival rate of 79.9%. Male sex was associated with poor prognosis. However, multivariate analysis showed no significant predictors. Treatment with corticosteroids significantly improved survival, especially with high doses (≥40 mg/day). Surgical intervention tended to correlate with poorer outcomes. These findings suggest that appropriately dosed corticosteroid therapy may enhance long-term prognosis in CCS. CONCLUSION: Using a comprehensive analysis of literature-based Cronkhite-Canada syndrome cases and our in-house cases, this study demonstrated the clinical characteristics of CCS. Our data showed the prognostic value of sex and surgical intervention, and the significance of high-dose corticosteroid therapy on the treatment of CCS.
Diagnosis of Gastric Intestinal Metaplasia: Histology, Endoscopy, and Artificial Intelligence.
Ahn BY, Kim JY, Chung H
Digestion · 2026 Feb · PMID 41746872 · Publisher ↗
BACKGROUND: Gastric intestinal metaplasia (GIM) is a well-established precancerous lesion and key biomarker for assessing the risk of gastric cancer. Histological classification into complete and incomplete types, along...
BACKGROUND: Gastric intestinal metaplasia (GIM) is a well-established precancerous lesion and key biomarker for assessing the risk of gastric cancer. Histological classification into complete and incomplete types, along with the Operative Link on Gastric Intestinal Metaplasia, provides valuable prognostic information, with stages III-IV strongly associated with cancer development. Therefore, an accurate diagnosis and appropriate surveillance of GIM are essential. SUMMARY: This review highlights the epidemiology, histological subtypes, and staging systems of GIM, and evaluates the performance of endoscopic modalities, including conventional white-light endoscopy (WLE), chromoendoscopy, and image-enhanced endoscopy (IEE). Conventional WLE has limited sensitivity and specificity for detecting GIM. In contrast, IEE techniques and scoring systems, such as the Endoscopic Grading of Gastric Intestinal Metaplasia (EGGIM), improve detection, demonstrate a strong correlation with histology, and enable endoscopic risk stratification. Although these methods increase the diagnostic yield, their accuracy remains dependent on operator experience and training. To address this limitation, artificial intelligence (AI) has attracted significant attention. Recent studies have reported that AI-assisted endoscopy achieves sensitivities and specificities exceeding 90%, often outperforming human endoscopists. AI applications extend beyond detection to real-time segmentation, automated EGGIM scoring, and pathological image analyses. However, challenges remain, including the need for external validation, management of data heterogeneity, generalizability beyond Asian cohorts, and development of explainable AI. KEY MESSAGES: (i) GIM is a critical biomarker for gastric cancer prevention that requires accurate diagnosis and surveillance. (ii) IEE techniques substantially improve endoscopic detection compared to WLE, although interobserver variability remains. (iii) AI demonstrates excellent diagnostic accuracy for GIM and may help overcome the human limitations in detection and grading. (iv) Future directions include prospective multicenter validation, real-time video-based AI, and integration of explainable and ethically sound AI systems into clinical practice.
Endoscopic Transpapillary Gallbladder Drainage Reduces the Frequency of Biliopancreatic Events in the Waiting Period for Surgery, Even in Patients without Comorbid Diseases.
Parlar YE, Öztürk B, Keskin O … +2 more , Kav T, Parlak E
Digestion · 2026 Feb · PMID 41746868 · Publisher ↗
INTRODUCTION: In patients with acute cholecystitis and choledocholithiasis undergoing endoscopic retrograde cholangiopancreatography (ERCP) followed by interval cholecystectomy (6 weeks-3 months), preoperative biliopancr...
INTRODUCTION: In patients with acute cholecystitis and choledocholithiasis undergoing endoscopic retrograde cholangiopancreatography (ERCP) followed by interval cholecystectomy (6 weeks-3 months), preoperative biliopancreatic events are reported in 18.3-41.8%. Endoscopic transpapillary gallbladder drainage (ET-GBD) is indicated in this patient group if there are comorbidities preventing surgery. This study compared biliopancreatic events during the interval to cholecystectomy in patients who underwent ET-GBD despite being surgically fit versus those treated with ERCP alone. METHODS: In this retrospective study conducted between 2018 and 2023, 121 patients with cholecystitis secondary to choledocholithiasis underwent ERCP. Surgical candidates expected to undergo delayed cholecystectomy were divided into two groups: those who received ET-GBD (study group) and those who did not (control group, from the first half of the study period). RESULTS: The ET-GBD group had a mean age of 54.54 (56.7% female), while the non-ET-GBD group had a mean age of 63.18 (50% female). During the waiting period, biliopancreatic events occurred in 1/34 (2.9%) of ET-GBD patients versus 18/34 (52.9%) of controls (absolute risk reduction: 50.0%, 95% confidence interval [CI]: 21.8-68.0; relative risk: 0.056, 95% CI: 0.0079-0.39; p < 0.001). Specifically, biliary colic (2.9% vs. 47.1%; p < 0.001), cholecystitis (0% vs. 17.6%; p = 0.009), and choledocholithiasis (0% vs. 26.4%; p = 0.001) were significantly less frequent in the ET-GBD group. CONCLUSION: ET-GBD was associated with significantly lower biliopancreatic complications during the interval to surgery in operable patients with acute cholecystitis and choledocholithiasis.
Disturbance of Lymphatic Function by Prox1 Contributes to Mesenteric Lesions and the Composition of Microbiota in Crohn's Disease.
Shen W, Li C, Liu R … +3 more , Huang X, Li Y, Zhu W
Digestion · 2026 Feb · PMID 41739728 · Publisher ↗
INTRODUCTION: The main aim of the current study was to investigate the potential role of Prox1 in lymphatic function and analyze Prox1-dependent stimulation of lymphatic function in experimental Crohn's disease (CD). MET...
INTRODUCTION: The main aim of the current study was to investigate the potential role of Prox1 in lymphatic function and analyze Prox1-dependent stimulation of lymphatic function in experimental Crohn's disease (CD). METHODS: Prox1flox/+, Tie2-CreERT2, and IL-10 KO mice were included. Lymphatic vessel density and lymphatic function were analyzed using immunohistochemistry and lymphangiography. The effects of lymphatic function on mesenteric adipose tissue (MAT) and the composition of microbiota were evaluated. Disease activity and enterocolitis inflammation were assessed using a grading system. RESULTS: For lymphatic vessel, IL-10 KO+Prox1 KO mice showed lower lymphatic vessel density and less functional lymphatic vessels. IL-10 KO+AAV-Prox1 mice showed significantly increased lymphatic vessel density. Delivery of AAV-Prox1 also promoted lymphatic drainage function. Additionally, Prox1-dependent stimulation of lymphatic function reduced hypertrophy of MAT in IL-10 KO mice. Delivery of AAV-Prox1 also modified the composition of microbiota; the proportion of Firmicutes increased and Bacteroidetes decreased in IL-10 KO+AAV-Prox1 mice compared with IL-10 KO mice. An increase in the diversity of gut microbiota in IL-10 KO+AAV-Prox1 mice was observed. Systemic delivery of AAV-Prox1 ameliorated disease activity index and the severity of gut inflammation in IL-10 KO mice. Without the compensatory response of Prox1, IL-10 KO+Prox1 KO mice developed serious inflammation in the colon. CONCLUSION: Prox1 played the critical role in lymphatic function. Additionally, Prox1-dependent stimulation of lymphatic function could reduce hypertrophy of MAT, modify the composition of microbiota, and ameliorate gut inflammation. Our findings demonstrated that correction of lymphatic function with Prox1 may lead to improved treatments for CD.
Childhood-Onset Celiac Disease Autoimmunity and Risk of Depression and Anxiety across the Lifespan: A Longitudinal Analysis of a Large Real-World Cohort.
Elimeleh Y, Buchris M, Awadie H … +3 more , Abu Hanna F, Rozenberg O, Rinawi F
Digestion · 2026 Feb · PMID 41712501 · Full text
INTRODUCTION: Celiac disease is associated with various extraintestinal manifestations, including psychiatric and psychological comorbidities. We evaluated the risk of developing depression and anxiety among patients dia...
INTRODUCTION: Celiac disease is associated with various extraintestinal manifestations, including psychiatric and psychological comorbidities. We evaluated the risk of developing depression and anxiety among patients diagnosed with celiac disease autoimmunity (CDA). METHODS: This retrospective case-control cohort study was conducted using the Clalit Healthcare Services population-based electronic database (∼4.5 million individuals). Between January 1, 2008, and December 31, 2022, we identified subjects aged 1-80 years with a positive IgA anti-tissue transglutaminase test and a repeat measurement within 6-36 months. Depression and anxiety were identified over follow-up using ICD-9 diagnostic codes or by documented regular use of antidepressants or anxiolytics. RESULTS: We identified 3,797 patients with CDA, and the cohort was matched in a 1:3 ratio with 11,387 healthy controls having a negative anti-tTG2 serology. Over a median 60-month follow-up duration, 5.9% of CDA patients developed depression or anxiety, compared to 1.7% of the control group (HR 2.89, 95% CI 2.2-3.8, p < 0.001), and 67% of anxiety and depression cases among CDA patients were developed during childhood. On multivariate analysis, very high baseline anti-tTG2 level (>10× ULN), older age at diagnosis, and female sex were independently associated with the risk of developing anxiety and depression among CDA patients (HR 1.82, 1.03, and 1.38; p values 0.029, 0.018, and 0.038, respectively). CONCLUSIONS: CDA appears to increase the risk for anxiety and depression, particularly with very high baseline anti-tTG2 levels, advanced age at diagnosis, and in females.
Gastric Cancer in the Post-<italic>Helicobacter pylori</italic> Era: Non-<italic>H</italic>. <italic>pylori</italic>-Related Gastric Microbiota, Non-<italic>H</italic>. <italic>pylori-</italic>Related and Post-<italic>H. pylori</italic> Eradication Gastric Cancer.
Tan AXH, Tee NCH, Ang TL
Digestion · 2026 Feb · PMID 41712480 · Publisher ↗
BACKGROUND: Helicobacter pylori-negative gastric cancer (GC) occurs in individuals with specific risk factors. This narrative review will evaluate the role of non-H. pylori gastric microbiota in gastric carcinogenesis an...
BACKGROUND: Helicobacter pylori-negative gastric cancer (GC) occurs in individuals with specific risk factors. This narrative review will evaluate the role of non-H. pylori gastric microbiota in gastric carcinogenesis and summarize the clinical aspects of non-H. pylori-related GC. SUMMARY: Epstein-Barr virus is the only other infection conclusively proven to be causative of GC. Case-control studies have reported a dysbiotic GC-associated gastric microbiome, with greater abundance of Fusobacterium nucleatum, Streptococcus anginosus, Prevotella, and Veillonella. Mice model mechanistic studies have demonstrated the role of non-H. pylori microbiota in gastric carcinogenesis. Current data support their role as promotive factors, with H. pylori infection being the initiating event. In hereditary GC, inherited germline mutations initiate a genetically programmed pathway to gastric carcinogenesis. Autoimmune atrophic gastritis and Ménétrier's disease are associated with increased GC risk. Oxyntic gland adenoma/gastric adenocarcinoma of fundic gland type and foveolar-type gastric adenoma are distinct histological subtypes of gastric neoplasia. Chronic atrophic gastritis (CAG) and gastric intestinal metaplasia (GIM) persist even after H. pylori eradication, increasing GC risk. KEY MESSAGES: There must be greater awareness of H pylori-negative GC as a diagnostic possibility due to the impact on management. There is significant potential for translational application of gastric microbiome as predictive or prognostic biomarkers or even to shape treatment outcomes. Endoscopic surveillance is indicated in the case of extensive CAG or GIM, even after successful H. pylori eradication.
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