Ulcerative colitis (UC) is a chronic inflammatory bowel disease affecting the colonic mucosa. Changes in mucin phenotype may be associated with mucosal inflammation in UC. However, the relationship between clinicopathological features and mucus phenotypes in UC remains unclear. Therefore, we aimed to evaluate the association between mucus phenotypes and clinicopathological features in patients with UC using immunohistochemistry, as well as their association with ultra-high magnification endocytoscopy (EC) classification. A total of 51 lower gastrointestinal endocytoscopy procedures were performed for 39 patients with UC between 2018 and 2022. MUC2 expression was positive in all biopsy specimens, whereas MUC1, MUC6, and CD10 expression was negative. MUC5AC was expressed in 51.3% of cases. MUC5AC positivity was associated with duration of disease, classification by clinical course, Mayo score, Mayo endoscopic subscore (MES), Nancy histological index, C-reactive protein levels, erythrocyte sedimentation rate, and EC classification at the patient level. At the specimen level, significant differences were observed in the Nancy histological index, MES, and EC classification. In multivariate analysis, the Nancy histological index showed a significant correlation.MUC5AC is strongly correlated with histopathological severity and may also be associated with clinical and endoscopic severity. The clinical significance of MUC5AC positivity remains a topic for future investigation.

OBJECTIVES:Simulation-based colonoscopy training may support early acquisition of insertion skills, but its clinical effect remains uncertain. We evaluated whether a self-directed curriculum using the mikoto colonoscopy simulator improved insertion performance in gastroenterology trainees. METHODS:In this multicenter cluster-randomized trial, 12 gastroenterology trainees from 11 institutions in Japan and Taiwan were assigned 1:1 to mikoto simulator training or standard training, with the trainee as the unit of randomization. Each trainee performed 35 colonoscopies; intervention-arm trainees additionally completed 100 self-directed simulator sessions over 2 weeks. The primary endpoint was post-training cecal intubation rate (CIR), compared using mixed-effects logistic regression with trainee as a random intercept and pre-training CIR as a covariate. RESULTS:A total of 420 colonoscopies were analyzed. Post-training CIR was 80.0% (72/90) in the mikoto group versus 77.8% (70/90) in controls (adjusted OR, 1.34; 95% confidence interval, 0.37-4.84; p = 0.606). Within the mikoto group, CIR increased from 60.0% to 80.0% (p = 0.003) and cecal intubation time decreased, but the group-by-period interaction was not significant. Detection outcomes were unchanged. CONCLUSIONS:Although the between-group difference in post-training CIR did not reach statistical significance, self-directed mikoto simulator training produced a significant within-group improvement in CIR and a parallel reduction in cecal intubation time, supporting it as a feasible and educationally meaningful adjunct to conventional colonoscopy training for gastroenterology trainees. TRIAL REGISTRATION:UMIN Clinical Trials Registry: UMIN000054647.

Background/Objectives: Ultra-high-magnification endoscopy (Endocyto) visualizes microscopic mucosal structures and has been proposed as a tool for assessing mucosal inflammation. We previously developed an endocytoscopic classification system (EC-A to EC-D) for grading the severity of inflammation. In this study, we investigated the relationship between endocytoscopic classification and microRNA (miRNA) expression in 36 patients with ulcerative colitis (UC). Methods: This cross-sectional study was conducted in two phases at two institutions. In the first phase, microarray analysis was performed on biopsy samples from patients with UC and healthy controls enrolled at Nagasaki University Hospital. In the second phase, 36 patients with UC who underwent total colonoscopy via Endocyto at Tottori University Hospital were included, and selected miRNAs were analyzed via quantitative polymerase chain reaction. Results: Differentially expressed miRNAs were identified, and four (miR-141-5p, miR-192-5p, miR-194-5p, and miR-215-5p) were downregulated in inflammatory areas. Notably, miR-192-5p expression was markedly lower in the EC-B and EC-C+D groups than in the EC-A group. Furthermore, expression of CXC motif ligand 2 (CXCL2), a pro-inflammatory chemokine, was upregulated in inflammatory tissues and negatively correlated with miR-192-5p expression. Conclusions: These results indicate that reduced miR-192-5p expression is inversely associated with CXCL2 expression and that, among the miRNAs examined, miR-192-5p downregulation most consistently corresponded to the endocytoscopic classification. Our findings suggest that Endocyto may serve as a real-time, in vivo adjunct for a histology-like assessment of mucosal inflammation; its clinical utility requires prospective validation.

Three technical refinements facilitated effective septotomy and diverticular reduction in Zenker's diverticulum, resulting in a safe procedure and favorable clinical outcome.

BackgroundThe Japanese Society for Helicobacter Research (JSHR) published the fifth edition of the guidelines for the management of Helicobacter pylori (H. pylori) infection in 2024 in Japanese language.MethodsThis edition of JSHR guidelines was first developed in accordance with the Minds Clinical Practice Guideline and Grading of Recommendations Assessment, Development, and Evaluation system. This was published after inviting public comments and external evaluations. Consensus on clinical questions (CQs) was achieved using the modified Delphi method.ResultsThere was no change in the basic policy that all H. pylori infectious diseases are indications for eradication. Nucleic acid amplification was added to the diagnostic methods. Effects of proton-pump inhibitors (PPIs) on diagnostic tests were updated. The superiority of potassium-competitive acid blockers to PPIs in 1-week triple therapy with amoxicillin and clarithromycin has been shown. A flowchart for eradication therapy was provided for use in real-world settings. For gastric cancer prevention, eradication in earlier age is recommended. The most appropriate test and treatment strategies for adolescents are also described. Some CQs concerning gastric cancer prevention were identified, although evidence level was insufficient to make recommendations based on clinical importance.ConclusionThe revised guidelines facilitate the appropriate management of H. pylori infection and gastric cancer prevention.

Plasmablastic lymphoma (PBL) is a rare and aggressive B-cell lymphoma with a poor prognosis and is typically linked to human immunodeficiency virus (HIV)-related immunodeficiency. PBL associated with ulcerative colitis (UC) is an extremely rare condition. We report the case of a 63-year-old HIV-negative woman with UC who developed colonic PBL after long-term mesalazine and budesonide treatment. She achieved complete remission following chemotherapy and abdominal radiotherapy, with no recurrence for more than three years. To our knowledge, this is the fourth reported case of UC-associated PBL and demonstrates the longest survival. Chemoradiotherapy may be an effective treatment for localized PBL.

BACKGROUND AND AIMS:Pediatric achalasia and peroral endoscopic myotomy (POEM) are not well investigated. This study aimed to examine the clinical characteristics of pediatric achalasia and evaluate the long-term outcomes of POEM. METHODS:We conducted a multicenter study across 14 high-volume centers, comparing the clinical characteristics of children (aged < 18 years) diagnosed with achalasia to those of adults (aged < 65 years). The POEM procedures and outcomes were also compared between the two groups. RESULTS:Of the 3421 patients with achalasia, 50 (1.5%) were children. Compared with adults, children had a shorter period to diagnosis (1.0 vs. 3.4 years; p < 0.001) and were more likely to be severely underweight (body mass index: 17.8 vs. 20.9 kg/m2; p < 0.001). However, children exhibited less esophageal dilation (46.0% vs. 64.1%; p = 0.013) and higher lower esophageal sphincter pressure (37.3 vs. 29.9 mmHg; p = 0.002). Notably, a significant failure to thrive was not observed in the pediatric group. The POEM procedure time was shorter for children compared to adults (58.0 vs. 83.0 min; p < 0.001). Clinical success rates were not significant between the two groups. Over the 5-year follow-up period, children had a lower incidence of reflux esophagitis following POEM compared to adults (11.0% vs. 26.4%; p = 0.013). CONCLUSIONS:Pediatric achalasia is rare and typically presents with early-stage manometric and esophagogastric features, along with severe systemic symptoms requiring an early diagnosis. POEM is a durable and effective treatment for pediatric achalasia, offering advantages such as shorter procedural times and a lower incidence of postprocedure reflux compared to adults.

BACKGROUND:Accurate endoscopic diagnosis of colorectal lesions is essential for clinical management. This prospective multicenter study assessed the impact of magnification endoscopy on real-time decision-making for colorectal lesions. METHODS:We included 419 patients with 876 colorectal polyps and assessed using three approaches: single (white light endoscopy, WLE), dual (WLE + narrow-band imaging with magnification endoscopy, NBIME), and triple (WLE + NBIME + pit pattern analysis using magnification chromoendoscopy or acetic acid-enhanced NBIME). Expert endoscopists provided histological predictions and confidence. Predictions were further classified into three management categories: surveillance (hyperplastic polyps), endoscopic resection (conventional adenomas, sessile serrated lesions [SSLs], traditional serrated adenomas [TSAs], T1a carcinoma), and surgical resection (T1b carcinoma). RESULTS:Lesions included 24 hyperplastic polyps, 654 conventional adenomas, 85 SSL/TSAs, 90 T1a carcinomas, and 23 T1b carcinomas. Histological prediction accuracy was 84.9%, 85.3%, and 87.4% (p = 0.35), and clinical diagnosis accuracy was 94.6%, 95.5%, and 96.5% (p = 0.17) for single, dual, and triple modalities, respectively, showing numerically higher values with additional modalities. High-confidence rates significantly increased with additional modalities (73.4%, 80.0%, 83.6%; p < 0.05), correlating with improved accuracy. In high-confidence cases, histological prediction accuracy was 93.3%, 92.7%, and 93.2%, compared to 66.5%, 60.6%, and 67.4% in low-confidence cases (p < 0.05). A similar trend was observed for clinical diagnosis, with accuracy of 98.3%, 97.9%, and 97.8% versus 85.0%, 85.7%, and 89.6% (p < 0.05). Confidence gain was associated with larger size in both single-dual and dual-triple transitions (p < 0.05), particularly ≥ 10 mm lesions. CONCLUSION:Magnification endoscopy has minimal impact on diagnostic accuracy but significantly enhances diagnostic confidence, aiding clinical decisions.

Abstract Background Peroral endoscopic myotomy (POEM) is an effective treatment for achalasia; however, accurately identifying the distal extent of myotomy remains a technical challenge. Indocyanine green with infrared imaging (ICG‐IRI) may facilitate the intraoperative visualization of the esophagogastric junction. Methods We evaluated 39 patients who underwent POEM using ICG‐IRI. The primary outcome was the success rate of ICG‐IRI, defined as a clear endoscopic visualization of fluorescence at the distal myotomy endpoint. The secondary outcomes included technical success, changes in integrated relaxation pressure, and Eckardt scores before and after treatment. Results The technical success rate was 100%, and ICG‐IRI was successful in 94.9% of the cases (37/39). The median integrated relaxation pressure decreased from 26.9 to 10.8 mmHg, and the median Eckardt score improved from 5.0 to 1.0 (both p < 0.01). No adverse events were attributed to the ICG‐IRI. Conclusions The ICG‐IRI method is a reliable visual aid for identifying distal myotomy endpoints during POEM. This technique may enhance the procedural accuracy and improve clinical outcomes.

OBJECTIVES:Achalasia is an esophageal motility disorder that impairs quality of life and is often missed (20-50%) on endoscopy. A newly developed computer-aided detection (CAD) software has shown high accuracy for achalasia diagnosis in preclinical settings. However, its benefit in a clinical setting remains unclear. METHODS:Between February and August 2023, 83 endoscopists from 27 centers assessed 50 randomized endoscopic videos (25 achalasia, 25 nonachalasia) without and with CAD. Endoscopists assessed videos without CAD, then with CAD after 2 months. The primary end-point was improvement in sensitivity for nonexperienced endoscopists (no endoscopic experience of achalasia). Sensitivity, specificity, and accuracy with and without CAD were compared using the McNemar test. RESULTS:Sensitivity for diagnosing achalasia increased significantly with CAD, rising from 74.2% (95% confidence interval [CI] 72.2-76.0%) to 91.2% (95% CI 89.9-92.4%) for all readers, showing a difference of 17.1% (95% CI 15.1-19.0%). Specifically, sensitivity improved from 66.9% (95% CI 63.6-70.0%) to 91.9% (95% CI 89.9-93.6%) among nonexperienced endoscopists, resulting in a difference of 25.0% (95% CI 21.7-28.4%), and from 79.5% (95% CI 77.1-81.8%) to 90.8% (95% CI 89.0-92.3%) among experienced endoscopists (endoscopic experience of at least one achalasia case), with a difference of 11.3% (95% CI 8.9-13.6%). Accuracy and specificity improved significantly with CAD assistance, regardless of reader's experience. CONCLUSION:CAD improves achalasia detection by 17%, confirming preclinical results. The benefit was higher for nonexperienced endoscopists. CAD assistance may lead to prompt and effective treatment, minimizing the risk of false-negative diagnosis in clinical practice. TRIAL REGISTRATION:This study was registered in the University Hospital Medical Information Network Clinical Trial Registry (https://www.umin.ac.jp/ctr/) number: UMIN000053047.

Objective Abdominal ultrasonography (AUS) is used to screen for abdominal diseases owing to its low cost, safety, and accessibility. However, the detection rate of pancreatic disease using AUS is unsatisfactory. We evaluated the visualization area of the pancreas and the efficacy of manipulation techniques for AUS with fusion imaging. Methods Magnetic resonance imaging (MRI) volume data were obtained from 20 healthy volunteers in supine and right lateral positions. The MRI volume data were transferred to an ultrasound machine equipped with a fusion imaging software program. We evaluated the visualization area of the pancreas before and after postural changes using AUS with fusion imaging and assessed the liquid-filled stomach method using 500 ml of de-aerated water in 10 randomly selected volunteers. Patients This study included 20 healthy volunteers (19 men and 1 woman) with a mean age of 33.0 (21-37.5) years old. Results Fusion imaging revealed that the visualization area of the entire pancreas using AUS was 55%, which significantly improved to 75% with a postural change and 90% when using the liquid-filled stomach method (p=0.043). Gastrointestinal gas is the main obstacle for visualization of the pancreas. Conclusion Fusion imaging objectively demonstrated that manipulation techniques can improve pancreatic visualization.

Background: Photodynamic therapy (PDT) has advanced through the utilization of photosensitizers and specific -wavelength light (>= 600 nm). However, the widespread adoption of PDT is still impeded by high equipment costs and stringent laser safety requirements. Porphyrins, crucial in PDT, have another absorbance peak of blue light (lambda = 380 - 500 nm). This peak corresponds to the wavelength of narrowband imaging (NBI) (lambda = 390 - 445 nm), an image -enhancement technology integrated into endoscopes by Olympus Medical Systems. The study aimed to investigate the potential of widely adopted NBI as a PDT light source for superficial cancers via endoscopes. Methods: Esophageal and biliary cancers were selected for investigation. Human esophageal cancer cell lines (KYSE30, KYSE70, KYSE170) and cholangiocarcinoma cell lines (HuCCT-1, KKU-213) were subjected to verteporfin-mediated PDT under NBI light (lambda = 390 - 445 nm). Assessments included spectrometry, crystal violet staining, and fluorescein imaging of singlet oxygen generation and apoptosis. Results: Verteporfin exhibited a peak (lambda = 436 nm) consistent with the NBI spectrum, suggesting compatibility with NBI light. NBI light significantly inhibited the growth of esophageal and biliary cancer cells. The half -maximum effective concentration (EC50 ) values (5 J/ cm(2) ) for KYSE30, KYSE70, KYSE170, HuCCT-1, and KKU-213 were calculated as 2.78 +/- 0.37 mu M, 1.76 +/- 1.20 mu M, 0.77 +/- 0.16 mu M, 0.65 +/- 0.18 mu M, and 0.32 +/- 0.04 mu M, respectively. Verteporfin ac cumulation in mitochondria, coupled with singlet oxygen generation and observed apoptotic changes, suggests effective PDT under NBI light. Conclusions: NBI is a promising PDT light source for superficial cancers via endoscopes.

Background/Objectives: Esophageal achalasia is an archetypal esophageal motility disorder characterized by abnormal peristalsis of the esophageal body and impaired lower esophageal sphincter (LES) relaxation. Methods: In this study, the mRNA expression of docking proteins 1 and 2 (DOK1 and DOK2, respectively) were analyzed and the mechanisms underlying achalasia onset were investigated. Results: DOK1 and DOK2 mRNA levels significantly increased in the LES of patients with achalasia. Moreover, significant correlations were observed between IL-1β and DOK1, IL-1β and DOK2, ATG16L1 and DOK1, and HSV1-miR-H1-3p and DOK2 expression levels. However, a correlation between ATG16L1 and DOK2 or between HSV-miR-H1-3p and DOK1 expression was not observed. In addition, a positive correlation was observed between patient age and DOK1 expression. Microarray analysis revealed a significant decrease in the expression of hsa-miR-377-3p and miR-376a-3p in the LES muscle of patients with achalasia. Conclusions: These miRNAs possessed sequences targeting DOK. The upregulation of DOK1 and DOK2 expression induces IL-1β expression in the LES of achalasia patients, which may contribute to the development of esophageal motility disorder.

BACKGROUND/AIM:Esophagogastroduodenoscopy (EGD) is an effective screening method for early detection of gastric cancer. The GAGLESS mouthpiece has a structure that widens the pharyngeal cavity and suppresses the pharyngeal reflex. This study aimed to investigate the acceptability, safety, and feasibility of transnasal and peroral ultrathin endoscopy using GAGLESS mouthpieces (Clinical Trial Number: UMIN000036922).PATIENTS AND METHODS:This study was a multicenter, prospective, randomized, open-label trial performed using a questionnaire. The study included 101 consecutive patients who visited the participating medical institutions between June 2019 and March 2022 (median age=47 years, range=24-87 years; all male). Patients aged ≥20 years at the time of consent acquisition who were the first to undergo EGD were included in the study. The primary endpoint was the degree of distress during EGD, as determined using a visual analog scale (VAS).RESULTS:The VAS score during endoscopic passage through the pharynx was significantly better in the transnasal endoscopy group than in the oral endoscopy group (2.420 vs. 4.092, p=0.001). There was no significant difference in the VAS scores between the two groups during anesthesia or throughout the examination. Compared with nasal endoscopy, oral endoscopy with a GAGLESS mouthpiece did not reduce the VAS score but did significantly improve gastric visibility.CONCLUSION:For patients in whom there was difficulty in inserting a nasal endoscope, using a GAGLESS mouthpiece rather than a conventional mouthpiece may be more useful in reducing pain.

Objectives High‐resolution manometry (HRM) and esophagography are used for achalasia diagnosis; however, achalasia phenotypes combining esophageal motility and morphology are unknown. Moreover, predicting treatment outcomes of peroral endoscopic myotomy (POEM) in treatment‐naïve patients remains an unmet need. Methods In this multicenter cohort study, we included 1824 treatment‐naïve patients diagnosed with achalasia. In total, 1778 patients underwent POEM. Clustering by machine learning was conducted to identify achalasia phenotypes using patients' demographic data, including age, sex, disease duration, body mass index, and HRM/esophagography findings. Machine learning models were developed to predict persistent symptoms (Eckardt score ≥3) and reflux esophagitis (RE) (Los Angeles grades A–D) after POEM. Results Machine learning identified three achalasia phenotypes: phenotype 1, type I achalasia with a dilated esophagus ( n = 676; 37.0%); phenotype 2, type II achalasia with a dilated esophagus ( n = 203; 11.1%); and phenotype 3, late‐onset type I–III achalasia with a nondilated esophagus ( n = 619, 33.9%). Types I and II achalasia in phenotypes 1 and 2 exhibited different clinical characteristics from those in phenotype 3, implying different pathophysiologies within the same HRM diagnosis. A predictive model for persistent symptoms exhibited an area under the curve of 0.70. Pre‐POEM Eckardt score ≥6 was the greatest contributing factor for persistent symptoms. The area under the curve for post‐POEM RE was 0.61. Conclusion Achalasia phenotypes combining esophageal motility and morphology indicated multiple disease pathophysiologies. Machine learning helped develop an optimal risk stratification model for persistent symptoms with novel insights into treatment resistance factors.

Symptom scales for achalasia after per-oral endoscopic myotomy (POEM) are lacking. This study aimed to propose a new scale based on the conventional Eckardt score (c-ES) and evaluate persistent symptoms that impair patients’ quality of life (QOL) post-POEM. Dysphagia, regurgitation, and chest pain frequencies were assessed using a 6-point scale modified-ES (m-ES) after POEM, with “occasional” symptoms on the c-ES further subdivided into three-period categories on m-ES. Symptom severity was further evaluated using a 5-point scale ranging from 1 to 5 points, with a score ≥ 3 points defined as persistent symptoms impairing QOL. We analyzed the correlation between the m-ES and severity score, diagnostic performance of the m-ES for persistent symptoms, and overlaps between each residual symptom. Overall, 536 patients (median follow-up period, 2.9 years) post-POEM were included in this multicenter study. Significant correlations were observed between the m-ES and severity scores for dysphagia (r = 0.67, p < 0.01), regurgitation (r = 0.73, p < 0.01), and chest pain (r = 0.85, p < 0.01). Twenty-six patients (4.9

BACKGROUND AND AIMS:We determined the factors influencing total capsule colonoscopy, adequate cleansing, and detectability of second-generation colon capsule endoscopy (CCE) for colorectal polyps or tumors (CRTs), adverse events, and acceptability. METHODS:Among 44 Japanese hospitals, 1006 patients with suspected or documented colorectal diseases who underwent CCE were enrolled prospectively. RESULTS:The total capsule colonoscopy rate was 86.1%. Age younger than 63 years (adjusted odds ratio [aOR], 1.525), male sex (aOR, 1.496), inflammatory bowel disease (aOR, 1.889), lavage intake on day -1 (aOR, 1.625), ≥1800-mL lavage intake on day 0 (aOR, .595), prokinetics on day 0 (aOR, .608), and ≥30-mL castor oil booster on day 0 (aOR, 1.734) were significant independent predictors. The overall adequate cleansing rate was 65.5%. Constipation (aOR, .527), lavage intake on day -1 (aOR, 1.822), laxative intake on day -1 (aOR, 2.616), and ≥1900-mL lavage intake on day 0 (aOR, 1.449) were significant independent predictors. The detection rates for patients with CRTs ≥6 mm and ≥10 mm were 92% (95% confidence interval, 84-97) and 89% (95% confidence interval, 78-96), respectively. Inadequate cleansing in the ascending colon (aOR, .184), ≥6-mm CRT in the transverse colon (aOR, 4.703), and ≥6-mm CRT in the left-sided colon (aOR, 32.013) were significant independent predictors. CCE retention occurred in 2 patients (.20%) requiring endoscopic and surgical interventions. In total, 63% of patients desired CCE for their next colonoscopy. CONCLUSIONS:CCE was relatively safe, well tolerated, and useful for detecting colorectal lesions when adequate bowel preparation was made. (Clinical trial registration number: UMIN000021936.).

The distribution of body weight in patients with achalasia and after peroral endoscopic myotomy (POEM) has not been investigated. The role of body weight assessment after treatment remains unclear. Using the multicenter achalasia cohort, the frequency of underweight (body mass index [BMI] < 18.5 kg/m2) and overweight (BMI ≥ 25.0 kg/m2) and their associated clinical characteristics were analyzed. After POEM, risk factors for insufficient- (underweight persistently) and excessive- (responded to overweight) weight gainers were investigated. The correlation between BMI-increase rate and severity of esophageal symptoms post-POEM was evaluated. Among 3,410 patients, 23.0