Digestion[JOURNAL]
Sun
200 papers
Epidemiology of Barrett's Neoplasia in Japan.
Iijima K
Digestion · 2026 · PMID 40938781 · Publisher ↗
BACKGROUND: With a 50-year delay compared to Europe and the USA, esophageal adenocarcinoma (EAC) began to increase in Japan around 2010, and it is expected to continue rising over the next few decades. This 50-year discr...
BACKGROUND: With a 50-year delay compared to Europe and the USA, esophageal adenocarcinoma (EAC) began to increase in Japan around 2010, and it is expected to continue rising over the next few decades. This 50-year discrepancy is primarily attributable to variations in the timing of the decline in Helicobacter pylori infection rates across the two regions, with the extent of obesity in Japan also exerting an influence on the projected increase in EAC. Currently, the incidence of EAC in Japan is approximately one-tenth to one-twentieth that observed in Europe and the USA. However, ongoing monitoring is essential to assess the potential for escalation of this cancer. Accurate estimation of the incidence of EAC in Barrett's esophagus (BE), a precancerous condition of EAC, is imperative for the establishment of appropriate endoscopic surveillance for early cancer detection. SUMMARY: The incidence of EAC in BE is largely determined by its length. In the Japanese population, BE with a length greater than 3 centimeters exhibits a high incidence of EAC and necessitates surveillance, while BE with a length less than 1 centimeter exhibits an exceptionally low incidence of EAC and is considered to require no surveillance. The challenge lies in determining the optimal approach for addressing BE with a length of 1-3 cm, which is observed in 5-15 percent of endoscopic examinees, necessitating careful consideration due to its significance. KEY MESSAGE: Since the EAC risk of BE varies greatly depending on its length, the need for surveillance and inspection intervals for BE in Japan should be defined by its length.
Family History as a Dominant Risk Factor for Uninvestigated Dyspepsia and Chronic Constipation: A Rome IV-Based Study among Japanese University Students.
Vu NTH, Quach DT, Luu MN … +8 more , Miyauchi S, Ishiuchi N, Nguyen DTN, Yoshino A, Miyake Y, Okamoto Y, Oka S, Hiyama T
Digestion · 2025 Sep · PMID 40920606 · Publisher ↗
INTRODUCTION: Uninvestigated dyspepsia (UD) and chronic constipation (CC) are common disorders of gut-brain interaction. However, limited research has assessed their risk factors in young adults, particularly the influen...
INTRODUCTION: Uninvestigated dyspepsia (UD) and chronic constipation (CC) are common disorders of gut-brain interaction. However, limited research has assessed their risk factors in young adults, particularly the influence of family history. This study investigated the associated factors for UD and CC, focusing on family history among Japanese university students. METHODS: A cross-sectional study was conducted at Hiroshima University. UD and CC were diagnosed using the Rome IV criteria. Multivariate logistic regression was performed to identify associated factors of UD and CC. RESULTS: Among 10,500 individuals participating in the annual health checkup, 7,496 responded to the web-based questionnaire, and 5,386 completed it. The mean age of the participants was 21.1 ± 4.1 years, with a male-to-female ratio of 1:1.17. The prevalence of UD and CC was 7.3% and 13.7%, respectively. Family history was associated with both UD (odds ratio [OR]: 4.29; 95% confidence interval [CI]: 3.17-5.79) and CC (OR: 2.77; 95% CI: 2.31-3.31). Depression and physical inactivity were shared associated factors. Alcohol consumption (OR = 2.36; 95% CI: 1.15-4.83) and smoking (OR = 1.59; 95% CI: 1.02-2.49) were identified as associated factors for UD, while female sex (OR = 2.00; 95% CI: 1.69-2.36) and short sleep duration (OR = 1.28; 95% CI: 1.09-1.50) were associated with CC. CONCLUSIONS: Family history was found to be a predominant factor associated with both UD and CC, with a relatively stronger association for UD. Our finding highlights the need to consider familial factors in future prevention and intervention strategies for UD and CC in young adults.
Magnifying Endoscopic Classification for Early Barrett's Neoplasia.
Ikenoyama Y, Hattori A, Fujiwara Y … +4 more , Nakamura M, Hamada Y, Horiki N, Nakagawa H
Digestion · 2026 · PMID 40920604 · Publisher ↗
BACKGROUND: Barrett's esophagus (BE) is becoming increasingly prevalent in both Western countries and Japan. Early diagnosis of Barrett's neoplasia remains challenging. Traditionally, the Seattle protocol, a four-quadran...
BACKGROUND: Barrett's esophagus (BE) is becoming increasingly prevalent in both Western countries and Japan. Early diagnosis of Barrett's neoplasia remains challenging. Traditionally, the Seattle protocol, a four-quadrant random biopsy method, has been recommended in Western guidelines. However, this approach has several limitations, including sampling errors, poor adherence, and a high procedural burden. Therefore, magnifying endoscopy has gained attention as a valuable tool for detecting and characterizing neoplastic lesions in patients with BE. SUMMARY: This review outlines historical and current developments in magnifying endoscopic classification systems for BE, with a focus on narrow-band imaging (NBI) and acetic acid chromoendoscopy in both Western countries and Japan. Although various NBI-based classifications have been proposed, their complexity and poor reproducibility have limited their widespread clinical adoption. Recently, simplified and standardized classification systems, including the Barrett's International NBI Group classification in the West and the Japan Esophageal Society-Barrett's esophagus classification in Japan, have been introduced. These systems adopt a binary framework, categorizing mucosal and vascular patterns as "regular" (non-neoplastic) or "irregular" (neoplastic). They are easy to apply and have demonstrated high diagnostic accuracy and substantial interobserver agreement. Further simplification and practical refinement are required for broader clinical implementation. KEY MESSAGES: Compared with other gastrointestinal cancers, the magnifying endoscopic diagnosis of Barrett's neoplasia remains technically demanding. However, based on a growing body of evidence, endoscopists should be encouraged to actively challenge this area. Continued efforts to simplify and validate the classification systems are essential for their widespread clinical use in BE surveillance.
Volatile Organic Compounds in Irritable Bowel Syndrome: Microbial Insights into Gut-Brain Dynamics and Clinical Applications.
Nguyen DC, Gonlachanvit S, Sukaram T … +1 more , Patcharatrakul T
Digestion · 2025 Sep · PMID 40906599 · Publisher ↗
BACKGROUND: Irritable bowel syndrome (IBS) affects 4.1% of the global population, posing a significant healthcare challenge due to its complex pathophysiology and limited treatment options. Gut microbiota-derived volatil...
BACKGROUND: Irritable bowel syndrome (IBS) affects 4.1% of the global population, posing a significant healthcare challenge due to its complex pathophysiology and limited treatment options. Gut microbiota-derived volatile organic compounds (VOCs) are increasingly recognized as key players in IBS, with the potential for noninvasive diagnostics and personalized management. SUMMARY: This review examines VOCs - such as short-chain fatty acids, hydrocarbons, and alcohols - as microbial metabolites influencing IBS through gut barrier function, inflammation, motility, and gut-brain signaling. Cross-sectional studies highlight the diagnostic accuracy of VOCs (area under the curve 0.76-0.99) in distinguishing IBS from healthy controls and conditions like inflammatory bowel disease, while longitudinal studies underscore their utility in predicting and reflecting microbial changes to microbiota-targeted therapies. Despite this promise, variability in study designs, methodological inconsistencies, and confounding factors hinder clinical translation. KEY MESSAGES: VOCs illuminate the microbial underpinnings of IBS and its gut-brain interactions, offering a pathway to precise diagnosis and treatment stratification. However, their full potential awaits standardized sampling, analytical protocols, and robust clinical trials to ensure reliability and applicability in IBS care.
Comparative Efficacy of Mycophenolate Mofetil vs. Azathioprine in Autoimmune Hepatitis: A Systematic Review and Meta-Analysis.
Ibrahim MM, Sawaf B, Hassan NAIF … +5 more , Moussa MH, Ibrahim M, Motawea KR, Elhadi M, Alastal Y
Digestion · 2025 Aug · PMID 40875669 · Full text
BACKGROUND: Azathioprine (AZA) is the standard treatment for both induction and maintenance of response in autoimmune hepatitis (AIH). However, lifelong administration is often required, and the combination therapy of pr...
BACKGROUND: Azathioprine (AZA) is the standard treatment for both induction and maintenance of response in autoimmune hepatitis (AIH). However, lifelong administration is often required, and the combination therapy of prednisolone and azathioprine raises significant concerns regarding efficacy and tolerability, especially given the high relapse rates following AZA cessation. Consequently, there is a need to explore alternative treatment options. This systematic review and meta-analysis compared the efficacy and safety of mycophenolate mofetil (MMF) versus AZA, combined with prednisolone, for treating AIH. METHODS: PubMed, Cochrane, Scopus, and Web of Science were searched to identify randomized clinical trials and cohort studies comparing AZA and MMF for treating AIH. Four studies compared steroid withdrawal and complete biochemical response (CBR) between the MMF and AZA groups. Subgroup analyses were performed based on age (above and below 50 years) and IgG levels (above and below 2400 mg/dL). RevMan (version 5.4) software was used for meta-analysis. RESULTS: Four studies (three cohort studies and one RCT) comprising 505 patients were included in the final analysis. The pooled analysis showed a statistically significant association between the MMF group and increased CBR compared with the AZA group (RR = 1.44, 95% CI = 1.03 to 2.01, p-value = 0.03), with no significant difference between the two groups regarding steroid withdrawal. Subgroup analysis by age revealed a significant association between the MMF group and increased CBR in patients over 50 years (RR = 1.63, 95% CI = 1.00-2.64, p-value = 0.05). IgG subgroup analysis revealed a significant association between the MMF group and increased biochemical remission compared with the AZA group in patients with IgG levels of less than 2400 mg/dL (RR = 1.63, 95% CI = 1.00-2.64, p-value = 0.05). CONCLUSION: The use of MMF was significantly associated with increased CBR compared to AZA in patients with AIH. Additionally, there was no significant association between the two groups regarding steroid withdrawal. Further research is needed to fully elucidate the optimal treatment strategy for AIH patients across different subpopulations.
Dialysis, Antithrombotics, and Lesion Location: Who Benefits Most from Gel Immersion Endoscopy in Gastric Endoscopic Submucosal Dissection?
Hayashi H, Kanno T, Yano T … +9 more , Akahoshi K, Owada J, Sekiguchi H, Ueno T, Nomoto Y, Fukuda H, Takahashi H, Ino Y, Yamamoto H
Digestion · 2025 Aug · PMID 40820412 · Full text
INTRODUCTION: Gel immersion endoscopy (GIE) is a technique used to maintain a clear view during gastric endoscopic submucosal dissection. We aimed to identify cases most likely to benefit from GIE for ESD bleeding by rev...
INTRODUCTION: Gel immersion endoscopy (GIE) is a technique used to maintain a clear view during gastric endoscopic submucosal dissection. We aimed to identify cases most likely to benefit from GIE for ESD bleeding by reviewing our clinical experience and determining the associated factors. METHODS: We retrospectively analyzed 470 lesions in 380 patients who underwent gastric ESD between October 2020 and March 2023. The patients were divided into conventional method (n = 433) and GIE groups (n = 37). We compared the clinical and pathological characteristics between the groups. Univariate and multivariate logistic regression analyses were used to identify factors associated with GIE use. Among the GIE group, hemostasis times under gas, water, and gel conditions were compared using the Kruskal-Wallis test. RESULTS: Multivariate analysis revealed that dialysis (odds ratio [OR]: 15.3), concurrent antiplatelet and anticoagulant use (OR: 9.5), and tumor location in the middle third (OR: 3.5), upper third (OR: 5.7), or remnant stomach (OR: 9.3) were independently associated with GIE use. No significant differences in overall hemostasis time were observed between gas, water, or gel. Of the nine bleeding events exceeding 300 s under gas immersion, seven achieved successful hemostasis by switching to GIE, with a median of 32 s to locate the source and 140 s to complete hemostasis. CONCLUSION: Dialysis, combined antithrombotic use, and certain tumor locations were key factors influencing GIE for ESD bleeding. Although the overall hemostasis times did not differ, GIE may be particularly beneficial in high-risk scenarios.
Current Management of Laparoscopic and Endoscopic Cooperative Surgery for Duodenal Neoplasia: Suitable Endoscopic Resection Approaches.
Yamamoto H, Yoshimizu S, Hayami M … +9 more , Tanaka K, Tamamushi M, Kido K, Kurihara W, Fukuyama C, Horiuchi Y, Yoshio T, Hirasawa T, Nunobe S
Digestion · 2025 Aug · PMID 40815097 · Publisher ↗
INTRODUCTION: Duodenal laparoscopic and endoscopic cooperative surgery (D-LECS) is a promising hybrid approach to managing duodenal neoplasia, including superficial non-ampullary duodenal epithelial tumors (SNADETs) and...
INTRODUCTION: Duodenal laparoscopic and endoscopic cooperative surgery (D-LECS) is a promising hybrid approach to managing duodenal neoplasia, including superficial non-ampullary duodenal epithelial tumors (SNADETs) and subepithelial lesions (SELs). This approach aims to reduce adverse events (AEs), such as delayed perforation, often associated with endoscopic submucosal dissection (ESD). Combining laparoscopic techniques for duodenal stabilization with precise endoscopic resection, D-LECS may provide safer and more comprehensive treatment. However, few studies have compared the outcomes of D-LECS with those of ESD and full-thickness resection (FTR), and suitable endoscopic resection approaches for D-LECS remain unclear. METHODS: We retrospectively reviewed records of 80 patients who underwent D-LECS for duodenal neoplasia at our institution between 2011 and 2024. Fifty-six patients underwent D-LECS with ESD for SNADETs (ESD group), whereas 24 underwent D-LECS with FTR for 16 SELs and 8 SNADETs (FTR group). All patients underwent en bloc resection, showing an overall R0 resection rate of 92.5%. RESULTS: There was no significant difference in overall incidence of Clavien-Dindo grade II or higher AEs between the ESD and FTR groups. However, the ESD group tended to have fewer cases of delayed gastric emptying and higher inflammatory response (p = 0.087 and p = 0.063, respectively). One patient in the FTR group experienced delayed perforation and 2 patients in the ESD group experienced delayed bleeding. However, these events were not significant. CONCLUSIONS: Both D-LECS with ESD and FTR were effective and safe. D-LECS with ESD may be a more suitable approach for SNADETs, whereas D-LECS with FTR is preferable for SELs.
E3 Ubiquitin Ligase NEDD4L Regulates the TGF-β1/Smad Signaling Pathway to Mediate High-Glucose and High-Fat-Induced Ferroptosis of Hepatocytes.
Li F, Yao J, Yao J … +3 more , Mou Y, Li D, Wei L
Digestion · 2025 Jul · PMID 40743910 · Publisher ↗
INTRODUCTION: The aim of the study was to explore the molecular mechanism of E3 ubiquitin ligase neural precursor cell-expressed developmentally downregulated 4-like (NEDD4L) regulating high-glucose and high-fat-induced...
INTRODUCTION: The aim of the study was to explore the molecular mechanism of E3 ubiquitin ligase neural precursor cell-expressed developmentally downregulated 4-like (NEDD4L) regulating high-glucose and high-fat-induced ferroptosis in hepatocytes via modulation of transforming growth factor (TGF)-β1/Smad signaling pathway. METHODS: Hepatocytes THLE-2 were cultured in high-glucose and high-fat medium to establish an in vitro nonalcoholic fatty liver disease model. This study detected cellular lipid deposition, cell viability, cellular superoxide dismutase (SOD) activity, glutathione (GSH), malondialdehyde (MDA), ferrous iron (Fe2+), reactive oxygen species (ROS) levels, and cellular mitochondrial membrane potential (MMP). Meanwhile, cellular NEDD4L, GPX4, ACSL4, SLC7A11, TGF-β1, TβRII, and p-Smad2/3 levels were detected by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot. In addition, TGF-β1-TβRII and NEDD4L-TβRII interactions were evaluated by co-immunoprecipitation. RESULTS: High-glucose and high-fat treatment led to ferroptosis in hepatocytes, manifested by decreased cell viability, SOD activity, and GSH level, increased MDA, Fe2+, and ROS levels, and reduced MMP. High-glucose and high-fat treatment downregulated NEDD4L expression in hepatocytes; by contrast, overexpression of NEDD4L alleviated ferroptosis in hepatocytes. NEDD4L inhibited TGF-β1 signaling by mediating TβRII ubiquitination and degradation. Besides, suppressed TGF-β1/Smad signaling pathway alleviated ferroptosis in hepatocytes, and NEDD4L could regulate hepatocyte ferroptosis by mediating TGF-β1/Smad signaling pathway. CONCLUSION: NEDD4L can inhibit high-glucose and high-fat-induced ferroptosis in hepatocytes through suppressing the TGF-β1/Smad signaling pathway via mediating TβRII ubiquitination and degradation.
Endoscopic Management of Barrett's Esophagus and Related Neoplasia in Japan.
Shimamura Y, Iwaya Y
Digestion · 2026 · PMID 40720939 · Publisher ↗
BACKGROUND: Barrett's esophagus (BE)-related neoplasia remains less prevalent in Japan than in Western countries; however, its incidence is steadily rising. While multimodal treatment - typically endoscopic resection (ER...
BACKGROUND: Barrett's esophagus (BE)-related neoplasia remains less prevalent in Japan than in Western countries; however, its incidence is steadily rising. While multimodal treatment - typically endoscopic resection (ER) followed by ablation - is the standard of care, ER alone remains the primary treatment strategy in Japan. With advances in endoscopic techniques, endoscopic submucosal dissection (ESD) has become the mainstay for managing BE-related neoplasia. This review outlines the current Japanese approach, focusing on indications, preoperative assessment, treatment outcomes, and post-resection surveillance practices within the Japanese clinical context. SUMMARY: Accurate endoscopic assessment, including the use of magnifying endoscopy with image-enhanced modalities, is central to Japanese practice due to the importance of complete resection of neoplasia in the absence of ablative therapy. While data on BE-related neoplasia remain relatively limited in Japan, several multicenter studies have demonstrated favorable outcomes for ESD in terms of resection quality, safety, and long-term survival, particularly in low-risk patients. However, challenges remain, including the lack of standardized surveillance protocols and considerable heterogeneity in clinical practice across institutions. The establishment of unified clinical pathways and evidence-based strategies will be essential to address the increasing burden of BE-related neoplasia in Japan. KEY MESSAGES: The incidence of BE and esophageal adenocarcinoma is increasing in Japan, although still significantly lower than in Western countries. Unlike the Western standard of combining ER with radiofrequency ablation (RFA), Japanese practice relies primarily on ESD as the main curative modality. RFA is not widely available in Japan, leading to a reliance on complete resection and more aggressive ER strategies. Surveillance strategies remain inconsistent, largely due to the lower disease prevalence and limited Japan-specific clinical evidence.
Future Perspective of Artificial Intelligence Diagnostics for Early Barrett's Neoplasia.
Roser DA, Ebigbo A
Digestion · 2026 · PMID 40716435 · Publisher ↗
BACKGROUND: Barrett's esophagus (BE) represents the only established precursor to esophageal adenocarcinoma. While endoscopic surveillance is a cornerstone of early detection, it remains limited by interobserver variabil...
BACKGROUND: Barrett's esophagus (BE) represents the only established precursor to esophageal adenocarcinoma. While endoscopic surveillance is a cornerstone of early detection, it remains limited by interobserver variability, sampling error, and variability in diagnostic yield. In recent years, artificial intelligence (AI) has emerged as a promising tool to improve the detection and characterization of neoplastic lesions in BE. SUMMARY: This review outlines the current landscape and future potential of AI applications in the endoscopic management of BE. Diagnostic systems employing convolutional neural networks and transformer-based architectures have achieved high performance for both lesion detection (CADe) and characterization (CADx), with several models externally validated in multicenter cohorts. The first CE-certified commercial system, CADU™, has further marked the entry of AI into clinical use. Emerging developments include AI tools for infiltration depth estimation, vessel detection during endoscopic submucosal dissection, post-therapeutic surveillance, and procedural quality assessment. Challenges related to generalizability, human-AI interaction, ethical implementation, and regulatory compliance are discussed in the context of clinical translation. KEY MESSAGES: (1) AI systems demonstrate high diagnostic accuracy and enable real-time assistance in BE surveillance. (2) In-domain pretrained models and transformer-based systems may improve robustness and adaptability. (3) Clinical applications are expanding beyond diagnostics to therapeutic guidance and posttreatment monitoring. (4) Successful implementation depends on rigorous validation, explainability, and integration into clinical workflows.
Characteristics of Magnifying Endoscopy with Narrow Band Imaging Findings in Gastric Cancer after <italic>Helicobacter pylori</italic> Eradication.
Horiuchi Y, Yamamoto N
Digestion · 2025 Jul · PMID 40695251 · Publisher ↗
BACKGROUND: Helicobacter pylori (H. pylori) eradication reduces the risk of gastric cancer development and is effective in patients with chronic atrophic gastritis. Recently, an increase in gastric cancer incidence has b...
BACKGROUND: Helicobacter pylori (H. pylori) eradication reduces the risk of gastric cancer development and is effective in patients with chronic atrophic gastritis. Recently, an increase in gastric cancer incidence has been observed in daily clinical practice in patients who have undergone H. pylori eradication. Therefore, continuous surveillance endoscopy is important for detecting gastric cancer after H. pylori eradication. In addition, endoscopic findings may differ between non-eradication and post-eradication gastric cancer. Magnifying endoscopy with narrow band imaging (ME-NBI) has been useful for the diagnosis of post-eradication gastric cancer, regardless of the histological type. However, there have been no comprehensive reports in this regard. Here, we aimed to clarify the characteristics of ME-NBI findings in gastric cancer following H. pylori eradication. SUMMARY: In differentiated- and mixed-type cancers (a mixture of differentiated and undifferentiated type), the cancer may be covered by noncancerous epithelium following H. pylori eradication; however, abnormalities can still be detected using ME-NBI. Therefore, ME-NBI is suitable for the diagnosis of post-eradication gastric cancer. In undifferentiated-type cancer, ME-NBI is more useful in diagnosing post-eradication gastric cancer than non-eradicated gastric cancer because of the clear contrast between cancerous and noncancerous areas following eradication. In addition, when non-eradicated gastric cancer is detected, rather than performing endoscopic submucosal dissection (ESD) or gastrectomy without eradication, it is beneficial to start patients on eradication therapy immediately and diagnose the disease extent with ME-NBI without awaiting the results of the eradication assessment and performing ESD or gastrectomy. This approach is expected to prevent misdiagnosis of the tumor size and reduce the positivity of the horizontal margin in ESD or gastrectomy. KEY MESSAGES: The number of post-eradication gastric cancer cases is expected to increase in comparison to non-eradicated gastric cancer cases, as H. pylori eradication is being widely used in chronic atrophic gastritis cases. Therefore, the diagnosis of post-eradication gastric cancer using ME-NBI is expected to gain importance in daily clinical practice.
The Impact of Endoscopic Closure Treatment on Outcomes in Patients with Esophageal Cancer-Associated Fistula: A Retrospective Analysis.
Dai Q, Zhao X, Lu W … +4 more , Wang Y, Cen J, Tao H, Peng L
Digestion · 2025 Jul · PMID 40690912 · Publisher ↗
INTRODUCTION: Esophageal cancer-associated fistula is strongly linked to elevated mortality. This study aims to investigate the impact of endoscopic closure on outcomes in patients with esophageal cancer-related fistula....
INTRODUCTION: Esophageal cancer-associated fistula is strongly linked to elevated mortality. This study aims to investigate the impact of endoscopic closure on outcomes in patients with esophageal cancer-related fistula. METHODS: We retrospectively analyzed the clinical data of patients with esophageal cancer-related fistula. These patients were categorized into endoscopic closure group and conservative treatment group. The Clinical Pulmonary Infection Score (CPIS) gap, duration of hospitalization, ICU admission rates, in-hospital mortality rates, and hospitalization costs were compared between endoscopic group and conservative group. Additionally, factors associated with post-fistula survival and healing were assessed. RESULTS: Univariate and multivariate COX regression analyses revealed that endoscopic closure could significantly improve short-term pulmonary infections based on CPIS gap (3 vs. 2; p = 0.004) but did not influence survival or fistula healing outcomes, and the hospitalization costs were elevated (USD 6,653 vs. USD 3,350; p = 0.005). Subgroup analysis focusing on esophagotracheal fistulas was also consistent with these results. Protective factors associated with improved survival prognosis included higher albumin levels (HR = 0.928, 95% CI: 0.875-0.984, p = 0.012), absence of bloodstream infections (positive blood culture [HR = 23.055, 95% CI: 5.193-102.357, p < 0.001]), non-T4 stage (T4 stage [HR = 1.792, 95% CI: 1.052-3.052, p = 0.032]), and no distant metastasis (distant metastasis [HR = 2.122, 95% CI: 1.127-3.996, p = 0.020]). Cervical esophageal fistula (upper [HR = 0.154, 95% CI: 0.041-0.570, p = 0.005]; middle [HR = 0.128, 95% CI: 0.027-0.609, p = 0.010]; lower [HR = 0.218, 95% CI: 0.052-0.902, p = 0.036]) was significantly associated with improved fistula healing outcomes, while a history of radiotherapy (HR = 0.265, 95% CI: 0.089-0.788, p = 0.017) was a risk factor for esophageal fistula healing. CONCLUSION: Our study indicates that multiple factors are significantly associated with the prognosis of patients with esophageal fistula. Endoscopic closure treatment effectively manages short-term infections, but it associates with higher hospitalization costs and does not significantly enhance long-term healing or survival prognosis.
Colorectal Polyp Size Measurement Faces Infinite Possibilities: Artificial Intelligence Is the Key.
Wang CL, Sui XY, Zeng Y … +10 more , Wu JY, Xing JJ, Zhang S, Wei JH, Chang K, Wu YT, Li ZS, Zhao SB, Bai Y, Yu ED
Digestion · 2025 Jul · PMID 40690911 · Full text
BACKGROUND: Colorectal neoplasia poses a severe health threat worldwide. The accurate measurement of polyp size is essential for risk stratification, selecting polypectomy techniques, and determining the surveillance int...
BACKGROUND: Colorectal neoplasia poses a severe health threat worldwide. The accurate measurement of polyp size is essential for risk stratification, selecting polypectomy techniques, and determining the surveillance interval. SUMMARY: The methods routinely used for measuring polyp size, including objective ex vivo measurement, subjective visual estimation by an endoscopist, and objective precise measurement using endoscopic instruments, all have limitations. Therefore, the integration of artificial intelligence (AI) with endoscopy has been explored as a promising method for measuring the size of colorectal polyps. However, current AI systems are limited to endoscopic reference media or nonprospective real-time measurements. Consequently, AI-assisted endoscopy for precise, real-time automatic measurement of colorectal polyp size holds great promise for the future. Nevertheless, further extensive studies are necessary. KEY MESSAGES: This review focuses on summarizing the advancements in colorectal polyp size research and further explores the potential of AI-assisted measurements.
Current Management of Duodenal Neoplasia: Endoscopic Treatment for Large Superficial Non-Ampullary Duodenal Epithelial Tumor.
Miyazaki K, Yahagi N, Kato M
Digestion · 2026 · PMID 40690901 · Publisher ↗
BACKGROUND: Superficial non-ampullary duodenal epithelial tumors (SNADETs) were previously considered rare. However, the widespread use of health checkup endoscopy, improvements in endoscopic imaging and heightened aware...
BACKGROUND: Superficial non-ampullary duodenal epithelial tumors (SNADETs) were previously considered rare. However, the widespread use of health checkup endoscopy, improvements in endoscopic imaging and heightened awareness of SNADETs among endoscopists have recently led to an increase in their detection rate. Particularly for large SNADETs, the possibility of including cancer must be considered, and thus, complete and reliable resection is essential. Although surgical resection has traditionally been the standard treatment, its high invasiveness has led to increased interest in less invasive endoscopic treatments. Nevertheless, due to the unique anatomical and physiological features of the duodenum, endoscopic treatment in the duodenum remains highly challenging and presents many technical difficulties. SUMMARY: This review provides a comprehensive overview of current endoscopic treatment options for large SNADETs, including conventional endoscopic mucosal resection (C-EMR), underwater endoscopic mucosal resection (U-EMR), cold snare endoscopic mucosal resection (CS-EMR), endoscopic submucosal dissection (ESD), and laparoscopic-endoscopic cooperative surgery, incorporating the latest clinical findings. While C-EMR, U-EMR, and CS-EMR are associated with lower technical difficulty and favorable safety, they tend to show lower en bloc resection rates and higher recurrence rates for large SNADETs when compared to ESD. In contrast, ESD offers higher en bloc resection rates but carries a greater risk of complications due to its technical complexity. To overcome these limitations, several techniques have been developed, such as the pocket-creation method, water pressure method, improved closure strategies for mucosal defects, and drainage with endoscopic nasobiliary and pancreatic drainage to prevent exposure to pancreatic juice and bile. KEY MESSAGES: Multiple endoscopic strategies are available for the treatment of large SNADETs. However, due to the rarity of the disease and variation in institutional expertise, a standardized treatment strategy has not yet been established. Endoscopic treatment for large SNADETs is technically very challenging and carries a high risk. Therefore, careful consideration of the indication for each treatment method, along with a full understanding of their respective advantages and disadvantages, is essential. In recent years, the safety of endoscopic resection has been gradually improving due to various technical innovations and better management of adverse events, making ESD, which offers a high en bloc resection rate, an increasingly reasonable treatment option.
Pathophysiology of Achalasia.
Rengarajan A, Bazarbashi AN, Gyawali CP
Digestion · 2026 · PMID 40639355 · Publisher ↗
BACKGROUND: Achalasia is a rare primary esophageal motility disorder of the esophageal smooth muscle, characterized by abnormal relaxation of the lower esophageal sphincter and associated with abnormal, spastic, or absen...
BACKGROUND: Achalasia is a rare primary esophageal motility disorder of the esophageal smooth muscle, characterized by abnormal relaxation of the lower esophageal sphincter and associated with abnormal, spastic, or absent esophageal body peristalsis. SUMMARY: The primary pathophysiological defect is abnormal esophageal inhibitory nerve function from neuronal death in the esophageal neuronal plexuses and ganglia that control esophageal smooth muscle peristalsis. This is a consequence of an autoimmune cytotoxic insult from molecular mimicry following an intercurrent viral infection, typically herpes simplex virus, varicella zoster virus, human papillomavirus, measles virus, and even the COVID-19 virus. Neuronal inflammation rather than death can lead to an imbalance between excitatory and inhibitory forces, and varying degrees of retained spastic, premature or even normal peristalsis in the smooth muscle esophageal body. Chagas disease caused by Trypanosoma cruzi, eosinophilic inflammation, direct infiltration with neoplastic cells from adjacent cancers, or humoral autoimmune destruction from distant cancers can also result in an achalasia-like syndrome. Mechanical obstruction from tight strictures, anti-reflux or bariatric surgery, and extrinsic compression can mimic the manometric features of achalasia. Chronic opioid medication usage can result in a clinical and pathophysiological syndrome identical to spastic achalasia. KEY MESSAGES: Careful clinical evaluation and judicious interpretation of esophageal function tests following pathophysiological principles can lead to an accurate diagnosis of achalasia, opening the door to durable permanent disruption of the malfunctioning esophageal smooth muscle and resulting in symptom relief.
Does 5-Aminosalicylic Acid Prevent Colorectal Cancer in Tumour Necrosis Factor: Treated Ulcerative Colitis? A Real-World Study.
Nishida Y, Hosomi S, Fujimoto K … +9 more , Kobayashi Y, Nakata R, Maruyama H, Ominami M, Nadatani Y, Fukunaga S, Otani K, Tanaka F, Fujiwara Y
Digestion · 2026 · PMID 40623373 · Publisher ↗
INTRODUCTION: Ulcerative colitis (UC) increases the risk of colorectal cancer (CRC). Although 5-aminosalicylic acid (5-ASA) has long been regarded as chemopreventive, it remains unclear whether 5-ASA therapy still confer...
INTRODUCTION: Ulcerative colitis (UC) increases the risk of colorectal cancer (CRC). Although 5-aminosalicylic acid (5-ASA) has long been regarded as chemopreventive, it remains unclear whether 5-ASA therapy still confers this benefit when used concomitantly with tumour necrosis factor (TNF) inhibitors. METHODS: We performed a retrospective cohort study using the nationwide Japanese Medical Data Vision database. Patients with UC who initiated TNF inhibitors were followed from the first TNF inhibitor prescription until CRC diagnosis or disenrollment. Concomitant 5-ASA use was defined as prescription within 90 days before or after TNF initiation. Cumulative incidence was compared with Kaplan-Meier curves and the log-rank test; hazard ratios (HRs) were estimated with multivariable Cox regression and inverse probability of treatment weighting (IPTW), adjusting for age, sex, primary sclerosing cholangitis (PSC), diabetes, obesity, immunomodulator use, type of TNF agent, and prior advanced therapy exposure. RESULTS: Among 9,919 eligible patients, 8,387 (84.6%) received concomitant 5-ASA. During follow-up (median 3.14 years), 161 CRC events occurred: crude incidence 3.67/1,000 person-years (with 5-ASA use) versus 4.58/1,000 person-years (without 5-ASA use) (p = 0.421). Concomitant 5-ASA was not associated with CRC risk (adjusted HR 1.25, 95% CI 0.76-2.04; IPTW-adjusted HR: 1.28, 95% CI: 0.78-2.11). Independent risk factors were older age, male sex, and PSC. CONCLUSIONS: We found no measurable chemopreventive benefit of concomitant 5-ASA in UC patients receiving TNF inhibitors during this treatment phase. Accordingly, 5-ASA need not be prioritised for CRC prevention at this stage. Longer observation is required to clarify any benefit beyond the early years of TNF inhibitors.
Management of Adverse Events Related to Endoscopic Resection for Superficial Non-Ampullary Duodenal Epithelial Tumors.
Dohi O, Ochiai T, Seya M … +7 more , Yamauchi K, Iwai N, Kobayashi R, Hirose R, Ghoneem E, Inoue K, Yoshida N
Digestion · 2026 · PMID 40618746 · Publisher ↗
BACKGROUND: Endoscopic resection (ER) is a minimally invasive alternative to surgical resection for superficial non-ampullary duodenal epithelial tumors (SNADETs); however, it carries a high risk of adverse events (AEs)...
BACKGROUND: Endoscopic resection (ER) is a minimally invasive alternative to surgical resection for superficial non-ampullary duodenal epithelial tumors (SNADETs); however, it carries a high risk of adverse events (AEs) due to the thin duodenal wall and the technical challenges of endoscopic maneuverability. This review discusses the management of intraoperative and delayed postoperative AEs associated with duodenal ER. SUMMARY: Various ER techniques for SNADETs, including cold snare polypectomy (CSP), endoscopic mucosal resection (EMR), underwater EMR (UEMR), and endoscopic submucosal dissection (ESD), present different risk profiles. CSP has a very low risk of AEs, while EMR and UEMR exhibit moderate AE risks (up to 18.7%) and high recurrence rates, particularly in cases of piecemeal resections. ESD enables high en bloc resection rates but is associated with a considerable risk of AEs (up to 45.5%). Intraoperative AEs can be managed endoscopically using various closure techniques. To prevent intraoperative AEs during ESD, the use of scissor-type knives and specialized methods such as the pocket-creation method and water pressure method may be employed. Delayed AEs require effective closure of mucosal defects to prevent delayed perforation, which poses a high risk of conversion to surgical intervention. KEY MESSAGES: Careful patient selection and implementation of preventive strategies are essential to minimize AEs and optimize the safety of duodenal ER. A comprehensive understanding of the risk profiles of different ER techniques, along with appropriate preventive measures, is critical for safe and effective treatment. A multidisciplinary approach involving experienced endoscopists, surgeons, and radiologists is crucial to optimizing patient outcomes.
The Endoscopic Diagnosis of Superficial Non-Ampullary Duodenal Epithelial Tumors Using White Light Imaging.
Toya Y, Matsumoto T
Digestion · 2026 · PMID 40618733 · Publisher ↗
BACKGROUND: The recognition of superficial non-ampullary duodenal epithelial tumors (SNADETs) has increased with advancements in endoscopic technology and increased awareness among clinicians. White light imaging (WLI) r...
BACKGROUND: The recognition of superficial non-ampullary duodenal epithelial tumors (SNADETs) has increased with advancements in endoscopic technology and increased awareness among clinicians. White light imaging (WLI) remains the primary diagnostic modality for SNADETs. However, data for standardized endoscopic diagnostic approaches are lacking. SUMMARY: SNADETs are typically identified by their whitish, flat-elevated appearance and are predominantly located in the descending duodenum. The whitish mucosa is referred to as milk white mucosa (MWM). Although biopsies are traditionally performed for the diagnosis, biopsies have limited sensitivity for histological grading and may cause submucosal fibrosis, which complicates subsequent endoscopic resection. SNADETs are classified as gastric, gastrointestinal, or intestinal mucin phenotypes. Gastric SNADETs are usually found in the pre-ampullary region and are typically lacking MWM, whereas intestinal-type SNADETs often exhibit MWM. Several endoscopic features under WLI, such as lesion color, size, surface depression, and morphology, are useful for predicting the grade of dysplasia. Features such as a submucosal tumor-like appearance, deep depression, and oral side location are important for assessing submucosal invasion. KEY MESSAGES: WLI plays an important role in the detection and initial assessment of SNADETs. Although differentiating SNADETs from other duodenal lesions using WLI alone remains challenging, understanding the endoscopic features associated with each mucin phenotype aids in accurate distinction of high-grade dysplasia from low-grade dysplasia. Future studies are warranted to establish a comprehensive endoscopic diagnostic system for SNADETs.
Clinical Value of the Symptom-Reflux Association on Secondary Treatment Outcomes in Patients with Abnormal Acid Reflux.
Takahashi S, Matsumura T, Sonoda M … +10 more , Ozaki T, Kaneko T, Horio R, Goto C, Kurosugi A, Ohta Y, Taida T, Kikuchi A, Okimoto K, Kato J
Digestion · 2026 · PMID 40609523 · Publisher ↗
INTRODUCTION: Multichannel intraluminal impedance and pH monitoring (MII-pH) is the gold standard for diagnosing gastroesophageal reflux disease (GERD). However, the clinical value of the symptom-reflux association (SRA)...
INTRODUCTION: Multichannel intraluminal impedance and pH monitoring (MII-pH) is the gold standard for diagnosing gastroesophageal reflux disease (GERD). However, the clinical value of the symptom-reflux association (SRA) obtained using MII-pH remains unknown. The current study aimed to investigate the effect of SRA on the efficacy of secondary treatment in refractory true GERD. METHODS: This study included patients who underwent MII-pH monitoring for evaluating proton pump inhibitor (PPI)- or potassium-competitive acid blocker (P-CAB)-refractory GERD symptoms and who were diagnosed with abnormal acid reflux (acid exposure time >6%). Patients with a positive symptom index (SI) and symptom association probability on the MII-pH monitoring were included in the SRA-positive group and the remaining ones in the SRA-negative group. The differences in the subsequent treatment efficacy between the two groups were retrospectively analyzed. Treatment efficacy was evaluated using the Frequency Scale for the Symptoms of GERD (FSSG) questionnaire. RESULTS: Of the 192 patients with PPI-/P-CAB-refractory GERD, 41 (21.4%) were diagnosed with abnormal acid reflux. Among them, 30 (7 in the SRA-positive group and 23 in the SRA-negative group) underwent symptom assessments before and after treatment. The SRA-positive group had a significantly greater symptom improvement after treatment compared with the SRA-negative group (FSSG score changes: -13.0 ± 6.5 vs. -5.4 ± 8.2, p = 0.016). CONCLUSIONS: SRA evaluation is effective in predicting secondary treatment outcomes in patients with abnormal acid reflux.
Pathophysiology of Gastroesophageal Reflux Disease.
Bertin L, Savarino V, Marabotto E … +3 more , Ghisa M, de Bortoli N, Savarino EV
Digestion · 2026 · PMID 40562014 · Full text
<p>Background: Gastroesophageal reflux disease (GERD) is a prevalent gastrointestinal disorder caused by the retrograde flow of gastric contents into the esophagus, leading to bothersome symptoms and complications. Its p...
<p>Background: Gastroesophageal reflux disease (GERD) is a prevalent gastrointestinal disorder caused by the retrograde flow of gastric contents into the esophagus, leading to bothersome symptoms and complications. Its pathophysiology is complex and multifactorial, and recent research has aimed to explain the heterogeneity of GERD phenotypes, each influenced by different underlying mechanisms that contribute to symptom presentation and disease progression. Summary: GERD arises from an imbalance between defensive mechanisms and disruptive factors. Key pathophysiological contributors include esophageal gastric junction dysfunction, transient lower esophageal sphincter relaxations, esophageal motility abnormalities, delayed gastric emptying, and thoracoabdominal pressure gradients. Mucosal damage is exacerbated by prolonged exposure to acid and bile, pepsin activity, and impaired esophageal volume and chemical clearance. Additionally, central and peripheral neural modulation influences symptom perception, with heightened visceral sensitivity and esophageal hypervigilance playing significant roles in symptom severity and treatment response. Emerging diagnostic techniques such as high-resolution manometry, impedance-pH monitoring, and EndoFLIP® are improving our ability to identify specific pathophysiological abnormalities, leading to more personalized approaches to GERD management. Key Messages: (i) GERD results from a multifactorial interplay between anatomical, functional, and neurophysiological mechanisms. (ii) Esophageal clearance, EGJ structure and function, acid exposure, mucosal resistance, and neural modulation are crucial determinants of symptom severity and disease progression. (iii) The presence of different phenotypes of the reflux disease (e.g., GERD, functional heartburn, and reflux hypersensitivity) underscores the need for individualized diagnostic and therapeutic strategies. (iv) Advances in diagnostic technologies enhance our understanding of GERD pathophysiology, facilitating tailored management approaches beyond acid suppression therapies. Future research should focus on refining GERD phenotyping and integrating mechanistic insights into personalized treatment paradigms. </p>.
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