Introduction

Barrett’s esophagus (BE) is known to be a precursor of esophageal and gastroesophageal junctional adenocarcinoma¹. Adenocarcinoma of the esophagus based on BE is still relatively rare in Japan, but the Westernization of dietary habits, the increase in obese patients, and the eradication of Helicobacter pylori (HP) infection may increase the number of cases in the future. In Japan, the prevalence of long-segmented BE (LSBE), which is common in the Western world, is relatively low, whereas SSBE is frequently observed². Atrophic gastritis (AG) caused by HP infection is also frequently observed in Japan, and the diagnosis of Japanese SSBE may be modulated by HPinfection/AG. In this study, we retrospectively investigated whether the morphology of SSBE could be influenced by HP status.

Aims & Methods

In our institution, 60 patients who had endoscopic ultra-short segmented Barrett’s esophagus (USBE; length of <1cm) were retrospectively collected and divided into two groups: 30 cases with AG caused by current HP infection (AG group) or without AG (non-AG group). As patient characteristics, we investigated age, sex, presence of reflux esophagitis (RE), presence of hiatus hernia, and use of proton pump inhibitor (PPI) therapy from the medical records. To objectively evaluate the roughness of the SCJ, we compared the morphology of USBE by measuring the respective perimeters of EGJ and SCJ, followed by the calculation of the SCJ/EGJ ratio. As a sub-analysis in the AG group, the SCJ/EGJ ratio was similarly compared in terms of the degree of AG (closed-type, n = 3; open-type, n = 27) according to the Kimura-Takemoto classification.

Results

In terms of patient characteristics, the median age was higher in the AG group than in the non-AG group (72 years old vs. 49 years old, p <0.001), and RE was less common in the AG group than in the non-AG group (3% vs. 36%, p = 0.004). There were no statistical differences between the two groups in sex, presence of hiatus hernia, and use of PPI. The mean SCJ/EGJ ratio was significantly higher in the AG group than in the non-AG group (2.26 vs. 1.43, p <0.001). In the sub-analysis, the mean SCJ/EGJ ratio was likely to be higher in open-type atrophy than in closed-type atrophy (2.33 vs. 1.58, p = 0.092).

Conclusion

In endoscopically diagnosed USBE, the circumference of SCJ appeared rough in the AG group, which suggested that the morphology of BE is influenced by HP infection and subsequent AG development. Particularly in Japan, simple rough margins of SCJ influenced by HP/AG may be estimated as USBE. In diagnosing BE, the morphological characteristics of SCJ and the HP/AG status should be taken into consideration.

References

1. Haggitt RC et al. Barrett's esophagus, dysplasia, and adenocarcinoma. Hum Pathol. 1994; 25: 982-93.
2. Manabe N et al. Does short-segment columnar-lined esophagus elongate during a mean follow-up period of 5.7 years? Dig Endosc. 2011; 23: 166-72.

Disclosure

There is no conflict of interest in this study.

Introduction

Currently, the Japanese guidelines for GISTs suggest endoscopic ultrasound-guided fine-needle aspiration for sampling the tissue of subepithelial tumors (SETs) and as a first-line technique. Mucosal incision-assisted biopsy (MIAB) is another tissue sampling technique; in this technique, the mucous membrane covering the SET is cut to expose and sample the tissue directly under direct visualization. However, the Japanese guidelines do not clearly state how to handle this technique, and the MIAB procedure has not been standardized, especially in technical aspects, the need for local injection to the submucosa before mucosal incision to prevent perforation, and the need for acid secretion inhibitors to prevent postoperative bleeding.

Aims & Methods

This systematic review and meta-analysis aimed to evaluate diagnostic ability and examine the efficacy of countermeasures to adverse events of MIAB for gastric SETs. We performed a literature search and identified 533 relevant articles. Eleven articles, including 339 lesions, were ultimately used in the meta-analysis. The primary endpoint was the pathological diagnostic rate of MIAB for gastric SETs, and the secondary endpoint was the incidence of adverse events. The efficacy of acid secretion inhibitors in preventing postoperative bleeding and that of local injection before incision to prevent perforation were also examined.

Results

Nine studies were performed in Japan and two in South Korea, of which only two were prospective studies. The mean age of the patients was 60.7 years, and 48.4% were male. In all studies, endoscopic ultrasound was performed to assess tumors before incision-assisted biopsy. The mucosal incision procedure was the same in all studies: The mucosal incision on the tumor was made, and tissue was sampled directly from the tumor using biopsy forceps; however, in all cases in eight articles and six cases in one article, a local injection of saline or glycerol into the submucosa before the mucosal incision was performed. Nine articles reported the closure of the incision using clips. The mean tumor diameter was 20.6 mm, and the pathological results included 150 GISTs, 70 leiomyomas, 11 schwannomas, 37 ectopic pancreas, three lipomas, three cases of inflammatory fibrotic polyp, two malignant lymphoma lesions, two glomus tumors, one neuroendocrine tumor, one adenocarcinoma, one old hematoma, and one renal cell carcinoma. In all cases in six articles and some in two, an intravenous or oral gastric acid suppressant such as esomeprazole or vonoprazan was administered after treatment. The pooled pathological diagnostic rate of MIAB for gastric SETs was 86.0% (95% confidence interval [CI]: 78.6–93.4; I² = 96%). The adverse event rate of the pooled population was 0.3% (95% CI: −1.15 – 1.76; I² = 0%). The acid secretion inhibitors significantly reduced postoperative bleeding (odds ratio: 0.06, 95% CI: 0.01– 0.66, P = 0.02). Perforation occurred in 0% and 2.6% of the local injection and non-local injection cohorts, respectively, and the pathological diagnostic rates were 50% and 66.7%, respectively.

Conclusion

MIAB is a reliable technique with a favorable diagnostic rate and few adverse events. Acid secretion inhibitors effectively prevent postoperative bleeding, but the effectiveness of local injection remains unclear. This technique is considered a robust tissue sampling method for gastric SETs.

References

None

Introduction

Despite increasing attention to the rising incidence of Barrett’s esophagus (BE) and its progression to esophageal adenocarcinoma (EAC) in Western populations, the interplay between host factors and epigenetic alterations, including DNA methylation, remains poorly characterized (1). DNA methylation changes are among the earliest and most consistent molecular events observed in BE and EAC, but it is not yet well understood whether these changes are systematically correlated with demographic variables such as age and gender (2).

Aims & Methods

In this study, we explore whether methylation-based molecular subtypes exist within BE and EAC and examine how they are distributed across gender and age groups, leveraging integrated analysis of publicly available datasets. This approach may reveal novel insights into inter-individual variability in the epigenetic landscape of esophageal disease.
DNA methylation data from three GEO datasets (GSE104707, GSE81334, GSE89181) comprising 153 BE and 60 EAC samples were used. Samples with complete diagnostic, age, and gender annotations were retained, and the corresponding metadata was harmonized and used to build a cross-cohort to ensure robustness. Our previously defined Barrett’s progression-associated signature (3) was used to construct a unified methylation matrix across datasets. Batch effects were evaluated and corrected using ComBat, adjusting for diagnosis, age, and gender. Consensus clustering was used to identify molecular subtypes, and associations between clusters and clinical covariates were assessed using Wilcoxon rank-sum tests with FDR correction. Methylation patterns and BE status were visualized to explore subtype-specific features.

Results

Cross-cohort individual and integrated analyses identified two distinct molecular clusters, defined by broad differences in mean DNA methylation across regions selected by the progression-associated signature. Statistically significant differences in mean methylation were observed in both female (FDR = 1.92 × 10⁻⁸) and male (FDR = 1.03 × 10⁻⁶) groups, indicating gender-specific methylation variation stratified by cluster. Age-stratified analyses further revealed significant inter-cluster methylation differences within the 50–60 (FDR = 1.9 × 10⁻⁶) and 60–70 (FDR = 5.2 × 10⁻⁴) age groups, with a modest effect also observed in the 70–80 group (FDR = 1.26 × 10⁻²). These findings suggest the presence of age-associated methylation drift and gender-related differences; however, neither appears sufficient alone to fully account for the observed methylation patterns across BE and EAC patients.

Conclusion

Aging and male gender are established risk factors for BE and EAC, yet their impact on the epigenetic landscape remains poorly defined. Our findings reveal consistent methylation-based clustering across gender and age groups, suggesting that DNA methylation profiles capture biologically relevant variation linked to these demographics. This supports the utility of methylation signatures for early detection and risk stratification. However, key limitations such as sample size imbalances and male overrepresentation reflect broader biases in BE/EAC research and underscore the need for more representative study designs. Further confirmation studies using prospectively collected clinical samples are currently ongoing (NCT06523374) to advance the development of robust, demographically inclusive methylation-based biomarkers.

References

1. Kailasam A, Mittal SK, Agrawal DK. Epigenetics in the Pathogenesis of Esophageal Adenocarcinoma. Clin Transl Sci. 2015 Aug;8(4):394–402.
2. Kaz AM, Wong CJ, Varadan V, Willis JE, Chak A, Grady WM. Global DNA methylation patterns in Barrett’s esophagus, dysplastic Barrett’s, and esophageal adenocarcinoma are associated with BMI, gender, and tobacco use. Clin Epigenetics. 2016;8:111.
3. Dehkordi NR, Higareda-Almaraz JC, Mancuso FM, Kruusmaa K, Bertossi A. 365. METHYLATION BIOMARKERS TO STRATIFY BARRETT’S ESOPHAGUS PATIENTS PROGRESSING AND NON-PROGRESSING TO ESOPHAGEAL ADENOCARCINOMA. Diseases of the Esophagus. 2024 Sep; 37(Supplement_1)

Disclosure

N. Riahi Dehkordi and K. Kruusmaa are employees of Universal Diagnostics d.o.o., Ljubljana, Slovenia
J.C. Higareda-Almaraz and F.M. Mancuso are employees of Universal Diagnostics S.A., Seville, Spain

Introduction

Peroral endoscopic myotomy (POEM) is a less invasive endoscopic treatment for stenotic diseases caused by oesophageal motility dysfunction. During this procedure, the insufflation gas supplied from the endoscope migrates to the abdominal cavity, resulting in pneumoperitoneum. For excessive pneumoperitoneum, transabdominal puncture should be performed to rapidly decrease the intraabdominal pressure. However, the timing of puncture depends subjectively on the operator’s decision.

Aims & Methods

In this study, we retrospectively analysed the factors leading to pneumoperitoneum and clarified the objective indicators to determine the timing of abdominocentesis. A total of 100 consecutive patients who underwent POEM at our hospital from October 2018 to December 2023 were included. In univariate analyses, patient-related (age, sex, body surface area [BSA], body mass index), disease-related (diagnosis, preoperative Eckardt score), and treatment-related factors (operator's POEM experience, myotomy length, peak end-tidal carbon dioxide concentration [ETCO₂]) were compared between Puncture and Nonpuncture groups. In these parameters, sex and BSA, which correlated with the intraabdominal space, and factors that were supposed to influence the severity of pneumoperitoneum and the need for subsequent abdominocentesis by showing p-values of less than 0.1 were enrolled for subsequent multivariate analyses.

Results

The mean age was 58 (standard deviation [SD], 19) and 51% of them were male. The mean Eckardt score was 6 (SD, 3). Most patients (n = 92, 92%) were diagnosed with oesophageal achalasia. The mean procedure time was 88 min (SD, 35 min). Abdominocentesis was performed in 65 patients (68%), who were allocated into the Puncture group. In the univariate analyses, the peak ETCO₂ was significantly higher in the Puncture group than in the Nonpuncture group (p <0.01). In the multivariate analyses using sex, BSA, and the peak ETCO₂, high peak ETCO₂ was a single independent factor associated with abdominocentesis (odds ratio = 1.25, 95% confidence interval: 1.11–1.41, p <0.01). The receiver operating characteristic curve indicated that the two groups were divided with a maximal area under the curve (0.76) when a cut-off value of the peak ETCO₂ was set at 44.5 mmHg (sensitivity, 0.79; specificity, 0.65).

Conclusion

This study demonstrated that the intraoperative ETCO₂ level was a significant independent factor related to severe pneumoperitoneum in POEM, and 45 mmHg of peak ETCO₂ was an optimal cut-off value to differentiate the Puncture group from the Nonpuncture group. This result should be clinically useful as an objective reference to determine abdominocentesis in patient with pneumoperitoneum due to CO₂ leakage to the abdominal space.

Introduction

​Endocytoscopy (ECS), an ultrahigh-magnification contact-type endoscopy, enables real-time visualization of gastrointestinal mucosal and neoplastic cells. As a result, ECS enhance diagnostic precision as a form of optical biopsy. However, the reliability of ECS diagnosis is contingent upon adequate staining, which remains a considerable challenge in the stomach due to the abundance of mucus and inflammatory exudates that hinder optimal visualization. Weak vital staining can easily reduce the reliability of ECS diagnosis. Texture and Color Enhancement Imaging (TXI), a digital image enhancement modality developed by Olympus, enhances three key imaging elements—brightness, texture, and color tone—to optimize lesion visualization even under suboptimal staining conditions. Consequently, TXI may augment the diagnostic utility of ECS.

Aims & Methods

The aim of this study was to evaluate whether TXI enhances the diagnostic performance of ECS in early gastric cancer. Twenty-eight patients with 30 gastric cancers scheduled for magnifying endoscopic examination at Nippon Medical School Tama Nagayama Hospital between February 2024 and March 2025 were prospectively enrolled. All ECS procedures were performed with GIF-H290EC (Olympus Co., Tokyo, Japan) and the video processors EVIS X1 (Olympus Co., Tokyo, Japan). For in vivo dyeing, double staining with crystal violet and methylene blue was used. ECS was performed with and without TXI in both cancer and non-cancerous legions. ECS observation is performed by first taking photographs without TXI, and then taking photographs of the same area using the TXI. From each lesion, five ECS images with and without TXI were selected, resulting in a blinded and randomized image catalog (comprising 300 images from 30 gastric cancers and 280 images from 28 non-tumor areas). Two endoscopists independently assessed the images using a numerical rating scale (NRS, 0–10) to evaluate the visibility of nuclear atypia and structural cellular atypia. Diagnostic accuracy was assessed against pathological diagnosis as the gold standard. ECS diagnoses were rendered based on previously established criteria, wherein lesions exhibiting high-grade atypia were classified as cancer (Kaise M, et al. Endoscopy. 2015).

Results

The overall accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for EGC diagnosis by the two endoscopists were 82.5%, 84.3%, 80.7%, 81.3%, and 83.8%, respectively. The rate of interobserver agreement between the two endoscopists was high, with a kappa coefficient of κ = 0.797. Notably, diagnostic accuracy was significantly higher in the TXI images compared to the non-TXI images (85.2% vs. 79.0%, p = 0.0027). While the NRS scores for structural atypia did not differ significantly between the TXI and non-TXI images (4.90 vs. 4.87, p = 0.61), the NRS scores for nuclear atypia were significantly elevated in the TXI images (6.88 vs. 5.88, p < 0.0001).

Conclusion

​The integration of TXI with ECS significantly enhances the visualization of nuclear atypia and improves diagnostic accuracy in the diagnosis of gastric cancer. This synergistic approach facilitates superior optical biopsy capabilities, enhancing its clinical utility in the endoscopic diagnosis of early gastric cancer.

References

Kaise M, Ohkura Y, Iizuka T, Kimura R, Nomura K, Kuribayashi Y, et al. Endocytoscopy is a promising modality with high diagnostic accuracy for gastric cancer. Endoscopy. 2015;47:19–25.

Introduction

Exposure to Helicobacter pylori (H. pylori) has been associated with a decreased risk of eosinophilic oesophagitis (EoE).

Aims & Methods

As the epidemiology of EoE is rapidly increasing, we conducted an updated systematic review and meta-analysis to determine the association between H. pylori infection and EoE. We searched MEDLINE, Scopus, and ISI Web of Science, through to November 2024.We included studies reporting the status of H. pylori infection in patients with and without EoE or oesophageal eosinophilia (EE). A random-effects model was used to pool estimates.

Results

Nineteen studies including 1.704.821 subjects were analysed. H. pylori infection was associated with a 46% lower risk of EoE/EE (OR: 0.54, 95% CI 0.43 to 0.67). Comparable findings were observed when subgrouping studies by location or design. A nonsignificantly decreased risk for EoE was observed in pediatric patients exposed to H. pylori (OR 0.57, 95% CI 0.26 to 1.24) and in studies using serology to diagnose H. pylori (OR: 0.41, 95% CI 0.16 to 1.04). We found a lower risk of EoE compared with the overall findings in studies that diagnosed H. pylori only by gastric biopsy (OR 0.43, 95% CI 0.25 to 0.74) and in those published after 2019 (OR 0.44, 95% CI 0.28 to 0.68).

Conclusion

In a large systematic review and meta-analysis, exposure to H. pylori was significantly associated with decreased risk of EoE. As a stronger protective effect was found in more recent studies, the epidemiology of this association may evolve and deserves to be further monitored.

Disclosure

FRP has received speaker fees, advisory board fees and travel grants from Bayer, MSD, Roche, Eisai, Ipsen, Astra-Zeneca, Gilead, Abbvie, Alfasigma. CC has received research support from GSK and AstraZeneca. EVS has served as speaker for Abbvie, Agave, AGPharma, Alfasigma, Aurora Pharma, CaDiGroup, Celltrion, Dr Falk, EG Stada Group, Fenix Pharma, Fresenius Kabi, Galapagos, Janssen, JB Pharmaceuticals, Innovamedica/Adacyte, Malesci, Mayoly Biohealth, Omega Pharma, Pfizer, Reckitt Benckiser, Sandoz, SILA, Sofar, Takeda, Tillots, Unifarco; has served as consultant for Abbvie, Agave, Alfasigma, Biogen, Bristol-Myers Squibb, Celltrion, Diadema Farmaceutici, Dr. Falk, Fenix Pharma, Fresenius Kabi, Janssen, JB Pharmaceuticals, Merck & Co, Reckitt Benckiser, Regeneron, Sanofi, SILA, Sofar, Synformulas GmbH, Takeda, Unifarco; he received research support from Pfizer, Reckitt Benckiser, SILA, Sofar, Unifarco, Zeta Farmaceutici. AG has served as consultant for Eisai S.r.l., 3PSolutions, Real Time Meeting, Fondazione Istituto Danone, Sinergie S.r.l. Board MRGE and SanofiS.p.A, and as speaker for Takeda S.p.A, AbbVie and Sandoz S.p.A, and as advisory board member for VSL3 and Eisai. MM has served as consultant for Norgine, received speaker fees and or travel grants from Norgine, Fujifilm,Aurora Biofarma and Malesci. GI has served as speaker for Alfa Sigma, Biocodex, Illumina, Malesci, Sofar and Tillotts Pharma, and as consultant/advisor for Biocodex, Malesci, and Tillots Pharma. The other authors have no potential competing interest to disclose.