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Background: A capsule endoscope does not allow the examiner to observe a lesion from the desired direction in real time. Objective: To develop a driving system for a self-propelling capsule endoscope (SPCE) by using a magnetic field. Setting: Experimental endoscopic study in a live dog model. Design and Interventions: A microactuator was developed with the aim of remote-control operation. We developed a driving system for SPCE by attaching a capsule endoscope to this medical microactuator and performed the following experiments. (1) We operated this SPCE by remote control in the stomach of a dog under sedation and obtained endoscopic images using a real-time monitoring system only. (2) We placed a hemostatic clip on the gastric mucosa and recorded images of this clip with the SPCE. (3) We also placed clips at 2 other sites in the stomach and asked the SPCE operator, who was unaware of the location of the clips, to identify the site, number, and color of the clips. Main Outcome Measurements: Evaluation of performance of a driving system for SPCE. Results: The operator was able to obtain endoscopic images with the SPCE in the stomach of a dog in vivo, in any desired direction, by remote control. SPCE produced clear images of the clips placed in the stomach. The operator was able to easily identify the site, number, and color of the clips. Limitations: Animal model. Conclusions: Our trial suggests the possibility of clinical application of the driving system for an SPCE using a magnetic field. [ABSTRACT FROM AUTHOR]

Endoscopic injection sclerotherapy (EIS) with ethanolamine oleate was performed in patients with esophageal varices either with (18 patients) or without (19 patients) pretreatment with haptoglobin. The serum levels of urea nitrogen, creatinine, and β2-microglobulin, the creatinine clearance, and the urinary levels of N-acetyl-β--D-glucosaminidase and urinary β2-microglobulin were measured before and after EIS. Indices of the glomerular filtration rate (serum levels of urea nitrogen, creatinine, β2-microglobulin; creatinine clearance) showed no significant changes after EIS in either the haptoglobin-treated or untreated groups. However, the increase in the urinary parameters after EIS (which are indices of renal tubular function) was suppressed in the haptoglobin-treated group (p < 0.005 for urinary β2-microglobulin). Our results indicated that the administration of haptoglobin has a prophylactic effect on renal tubular dysfunction associated with the use of ethanolamine oleate in EIS. [ABSTRACT FROM AUTHOR]

The only reliable factor that reduces the risk of colorectal carcinogenesis is physical activity. However, the underlying mechanisms remain unclear. In this study, we examined the effects of physical activity against gut microbiota, including mucosa-associated microbiota (MAM) on azoxymethane-induced colorectal tumors in obese mice. We divided the subjects into four groups: normal diet (ND), high-fat diet (HFD), ND + exercise (Ex), and HFD + Ex groups. The Ex group performed treadmill exercise for 20 weeks. Thereafter, fecal and colonic mucus samples were extracted for microbiota analysis. DNA was collected from feces and colonic mucosa, and V3-V4 amplicon sequencing analysis of the 16SrRNA gene was performed using MiSeq. The HFD group had significantly more colonic polyps than the ND group (ND 6.5 ± 1.3, HFD 11.4 ± 1.5, p < 0.001), and the addition of Ex suppressed the number of colonic polyps in ND and HFD groups (ND 6.5 ± 1.3, ND + Ex 2.8 ± 2.5, p < 0.05). The HFD group showed significantly lower concentrations of succinic, acetic, butyric, and propionic acids (mg/g) in feces, compared with the ND group (succinic acid HFD 0.59, ND 0.17; acetic acid HFD 0.63, ND 2.41; propionic acid HFD 0.10, ND 0.47; and N-butyric acid HFD 0.31, ND 0.93). In the case of ND, succinic acid and butyric acid tended to decrease with Ex (succinic acid ND 0.17, ND + Ex 0.12; N-butyric acid ND 0.93, ND + Ex 0.74 0.74). Succinic acid, acetic acid, butyric acid, and propionic acid levels in feces were significantly lower in the HFD group than in the ND group; in both feces and mucus samples, Butyricicoccus and Lactobacillus levels were significantly lower in the HFD group. Akkermansia was significantly increased in ND + Ex and HFD + Ex groups. Diet and exercise affected the number of colorectal tumors. Furthermore, diet and exercise alter intestinal MAM, which may be involved in colorectal tumor development., Competing Interests: The authors declare no conflicts of interest.

Objectives: Endoscopic submucosal dissection (ESD) for superficial esophageal squamous cell carcinoma (ESCC) is performed for the treatment of lesions with varied backgrounds and factors. However, the predictive factors associated with the technical difficulty of ESD remain unknown in patients with varied lesions. Therefore, this study aimed to identify the predictive factors associated with the technical difficulty of ESD for ESCC using a retrospective cohort., Methods: This multicenter, retrospective study was conducted in 10 hospitals in Japan. Consecutive patients who underwent esophageal ESD between January 2013 and December 2019 were enrolled. Lesions of subepithelial tumors, adenocarcinoma, and adenoma were excluded. Difficult lesions were defined as ESD requiring a long procedure time (≥120 min), perforation development, piecemeal resection, or discontinued ESD. In the present study, the clinical factors were assessed to identify the technical difficulty of ESD using univariate and multivariate analyses., Results: Among 1708 lesions treated with esophageal ESD, eight subepithelial tumors, 44 adenocarcinomas, and two adenomas were excluded. Finally, 1505 patients with 1654 lesions were analyzed, and 217 patients with 217 lesions (13.1%) were classified as patients with difficult lesions. In multivariate analysis, the predictive factors associated with the technical difficulty of ESD were as follows: tumors with varices, tumors with diverticulum, antiplatelet use (discontinued), circumference of tumor (≥1/2), preoperative tumor size ≥30 mm, trainee, and nonhigh-volume center., Conclusion: This multicenter retrospective study identified the predictive factors associated with the technical difficulty of ESD for ESCC with varied backgrounds and factors., (© 2023 Japan Gastroenterological Endoscopy Society.)

Objective We assessed the factors associated with overlap between functional dyspepsia (FD) and nonerosive reflux disease (NERD) in endoscopy-based Helicobacter pylori-uninfected Japanese health checkup participants. Methods We utilized baseline data from 3,085 individuals who underwent upper endoscopy for health screening in a prospective, multicenter cohort study. The participants were asked to complete a questionnaire detailing their upper abdominal symptoms and lifestyle. Anxiety was assessed using the State-Trait Anxiety Inventory (STAI) score. FD, postprandial distress syndrome (PDS), and epigastric pain syndrome (EPS) were defined according to the Rome III criteria. NERD was defined as heartburn or regurgitation ≥1 day/week without erosive esophagitis. Results Of the 3,085 participants, 73 (2.4%), 97 (3.1%), and 84 (2.7%) had FD alone, NERD alone, and FD-NERD overlap, respectively. Factors associated with FD-NERD-overlap participants compared with participants with neither FD nor NERD were women [odds ratio (OR): 2.08, 95% confidence interval (CI): 1.24-3.52], body mass index (BMI) <18.5 (OR: 2.87, 95% CI: 1.56-5.07), alcohol consumption ≥20 g/day (OR: 1.85, 95% CI: 1.06-3.15), and a high STAI score (OR: 2.53, 95% CI: 1.62-4.00). Increasing age (OR: 1.06, 95% CI: 1.01-1.11) and EPS symptoms [pure EPS (OR: 3.67, 95% CI: 1.65-8.51) and PDS-EPS overlap (OR: 11.6, 95% CI: 4.09-37.2)] were associated with FD-NERD overlap vs. FD alone. Women (OR: 3.17, 95% CI: 1.47-7.04), BMI <18.5 (OR: 3.03, 95% CI: 1.04-9.90), and acid reflux symptoms ≥2 days a week (OR: 3.57, 95% CI: 1.83-7.14) were associated with FD-NERD overlap vs. NERD alone. Conclusion Understanding the clinical features of overlap between FD and NERD will lead to better management.

Fecal microbiota is a significant factor determining the cause, course, and prognosis of Crohn's disease (CD). However, the factors affecting mucosa-associated microbiota (MAM) remain unclear. This retrospective study examined the differences in ileal MAM between CD patients and healthy controls and investigated the factors affecting MAM in CD patients to clarify potential therapeutic targets. Ileal MAM was obtained using brush forceps during endoscopic examination from 23 healthy controls and 32 CD patients (most were in remission). The samples' microbiota was profiled using the Illumina MiSeq platform. Compared to controls, CD patients had significantly reduced α -diversity in the ileum and a difference in β -diversity. The abundance of butyric acid-producing bacteria in the ileal MAM was significantly lower in CD patients with a history of abdominal surgery than in those without. Because butyric acid is a major energy source in the intestinal epithelium, its metabolism via β-oxidation increases oxygen consumption in epithelial cells, reducing oxygen concentration in the intestinal lumen and increasing the abundance of obligate anaerobic bacteria. The suppression of obligate anaerobes in CD patients caused an overgrowth of facultative anaerobes. Summarily, reducing the abundance of butyric acid-producing bacteria in the ileal MAM may play an important role in CD pathophysiology.

Compositional changes in the microbiota are associated with various inflammatory diseases, including ulcerative colitis (UC). Aim: This study aimed to investigate the mucosa-associated microbiota (MAM) in patients with UC and its difference related with disease activity and classification. Brush samples were collected from the terminal ileum and sigmoid colon during endoscopic procedures. The microbiota of samples was profiled using the Illumina MiSeq platform. The V3-V4 regions of the gene encoding 16S rRNA (460 bp) were amplified using PCR. Fifty UC patients and twenty healthy controls were enrolled. UC patients displayed significantly reduced α-diversity in both the ileum and sigmoid colon compared to controls. A difference in β-diversity in the unweighted analysis was observed between the two groups. The abundance of Lactobacillus and Veillonella was significantly higher and that of Butyricicoccus , Ruminococcus and Lachnospiraceae was significantly lower in the ileum of UC patients than in controls. The abundance of Odoribacter in the ileum was significantly lower in left-sided colitis and pancolitis patients than in proctitis patients and lower in patients with highly severe disease activity than with mild disease activity. The reduction in abundance of butyric acid-producing bacteria, especially Odoribacter , in ileal MAM may play an important role in the pathophysiology of UC., Competing Interests: YN received scholarship funds from Taiyo Kagaku Co., Ltd. and from EA Pharma Co. Ltd.; a collaboration research fund from Taiyo Kagaku Co., Ltd.; and received lecture fees by Mylan EPD Co., Takeda Pharma. Co. Ltd., Mochida Pharma. Co. Ltd., EA Pharma Co. Ltd., Otsuka Pharma. Co. Ltd., and Miyarisan Pharma. Co. Ltd. The present research was partly supported by these funds. Neither the funding agency nor any outside organization has participated in the study design or have any competing interests. These companies have approved the final version of the manuscript. All authors except for YN received no support, financial or otherwise, from any organization that may have an interest in the submitted work. There are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2023 JCBN.)

Image-enhanced endoscopy (IEE) plays an important role in the detection and further examination of gastritis and early gastric cancer (EGC). Linked color imaging (LCI) is also useful for detecting and evaluating gastritis, gastric intestinal metaplasia as a pre-cancerous lesion, and EGC. LCI provides a clear excellent endoscopic view of the atrophic border and the demarcation line under various conditions of gastritis. We could recognize gastritis as the lesions of the diffuse redness to purple color area with LCI. On the other hand, EGCs are recognized as the lesions of the orange-red, orange, or orange-white color area in the lesion of the purple color area, which is the surround atrophic mucosa with LCI. With further prospective randomized studies, we will be able to evaluate the diagnosis ability for EGC by IEE, and it will be necessary to evaluate the role of WLI/IEE and the additional effects of the diagnostic ability by adding IEE to WLI in future.

Introduction: Favorable long-term outcomes of endoscopic submucosal dissection (ESD) for early remnant gastric cancer (ERGC) have been reported in single-center studies from advanced institutions. However, no studies have examined the long-term outcomes using a multicenter database. This study aimed to investigate the long-term outcomes of the aforementioned approach using a large multicenter database., Methods: This retrospective multicenter cohort study included 242 cases with 256 lesions that underwent ESD for ERGC between April 2009 and March 2019 across 12 centers. We investigated the long-term outcomes of these patients with the Kaplan-Meier method, and the relationship between curability, additional treatment, or hospital category, and the survival time was evaluated using the log-rank test., Results: During the median follow-up period of 48.4 months, the 5-year overall survival rate was 81.3%, and the 5-year gastric cancer-specific survival rate was 98.1%. The survival time of patients of endoscopic curability (eCura) C-2 without additional surgery was significantly shorter than the corresponding of patients of eCura A/B/C-1 and eCura C-2 with additional surgery. There was no significant difference in either overall survival or gastric cancer-specific survival rate between the high-volume and non-high-volume hospitals., Conclusion: The gastric cancer-specific survival of ESD for ERGC using a multicenter database was favorable. ESD for ERGC is widely applicable regardless of the hospital case volume. Management in accordance with the latest guidelines will lead to long-term survival., (© 2023 S. Karger AG, Basel.)

Most studies on the gut microbiome of Crohn's disease have been conducted using feces, instead of intestinal mucus to analyze the mucosa-associated microbiota. To investigate the characteristics of mucosa-associated microbiota in Crohn's disease patients and the effect of anti-tumor necrosis factor (TNF)-α therapy on mucosa-associated microbiota, we analyzed microbiota in Crohn's disease patients using brushing samples taken from terminal ileum. The recruited subjects were 18 Crohn's disease patients and 13 controls. There were 10 patients with anti-TNF-α therapy in Crohn's disease group. Crohn's disease patients had significantly reduced α-diversity in Shannon index compared to the controls. The comparative analysis of the taxonomic composition at the genus level between the Crohn's disease group and the controls indicated that butyrate-producing bacteria were less abundant in the Crohn's disease group compared to the controls. There were no differences in the diversity between the patients taking anti-TNF-α therapy and the patients without. The comparative analysis of the taxonomic composition at the genus level between the two groups indicated that some of anti-inflammatory bacteria were less abundant in the anti-TNF-α therapy group than the other. Reduction of specific bacteria producing anti-inflammatory molecules, especially butyrate-producing bacteria may play important roles in the pathophysiology of Crohn's disease., Competing Interests: No potential conflicts of interest were disclosed., (Copyright © 2022 JCBN.)

Background: Endoscopic submucosal dissection (ESD) for remnant gastric cancer (RGC) after distal gastrectomy (DG) is considered technically challenging due to the narrow working space, and severe fibrosis and staples from the previous surgery. Technical difficulties of ESD for RGC after DG have not been thoroughly investigated. This study aimed to develop and validate a risk-scoring system for assessing the technical difficulty of ESD for RGC after DG in a large multicenter cohort., Methods: We investigated patients who underwent ESD for RGC after DG in 10 institutions between April 2008 and March 2018. A difficult case was defined as ESD lasting ≥ 120 min, involving piecemeal resection, or the occurrence of perforation during the procedure. A risk-scoring system for the technical difficulty of the procedure was developed based on multiple logistic regression analyses, and its performance was internally validated using bootstrapping., Results: A total of 197 consecutive patients with 201 lesions were analyzed. There were 90 and 111 difficult and non-difficult cases, respectively. The scoring model consisted of four independent risk factors and points of risk scores were assigned for each as follows: tumor size > 20 mm: 2 points; anastomosis site: 2 points; suture line: 1 point; and non-expert endoscopist: 2 points. The C-statistics of the scoring system for technical difficulty was 0.72., Conclusions: We developed a validated risk-scoring model for predicting the technical difficulty of ESD for RGC after DG that can contribute to its safer and more reliable performance., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objectives: Lubiprostone is an apical type 2 chloride channel activator approved for the treatment of chronic constipation (CC), and nausea is the most common adverse symptom. However, the associated factors with the efficacy and the precise mechanism of nausea remain unclear. The aim of this study is to characterize clinical backgrounds related with the efficacy and the adverse symptoms of lubiprostone., Materials and Methods: Subjects were patients with CC who were prescribed lubiprostone from April 2017 to October 2019. The efficacy and safety of lubiprostone were retrospectively examined using the electronic medical record., Results: Hundred and fifty-five patients (76 men, and mean age 69) were evaluated. Lubiprostone was effective in 74 patients (47.8%), and the discontinuation due to adverse in 34 patients (21.9%). including nausea, diarrhea and abdominal pain in 16, 12 and 3 patients, respectively. The efficacy was significantly associated with gender, age, body mass index (BMI), diabetes mellitus, hypertension, calcium channel blockers and antipsychotics. In multivariate analysis, the efficacy was significantly associated with men (odds ratio [OR], 3.21; 95% confidence interval (CI), 1.42-7.27) and BMI (OR, 1.14; 95% CI, 1.02-1.28). The incidence of nausea was higher in patients under 65 years old, and hypertension was the significant protective factor for nausea., Conclusions: Lubiprostone was effective for men patients with CC, and hypertension seems to be the protective factor for nausea.

Background and Aim: The usefulness of a radio-tag-free PillCam patency capsule (PatCap) has been reported to evaluate the patency of the small intestine. If the PatCap is not excreted within 33 h, the location of the failed PatCap must be confirmed. Although several methods for locating the failed PatCap have been reported, a universal method has not been established. In this study, we aimed to confirm the clinical feasibility of abdominal ultrasonography combined with abdominal X-ray in the determination of the location of a failed PatCap., Patients and Methods: Consecutive patients who were scheduled to undergo the capsule endoscopy and had received PatCap examination between July 2012 and September 2019 were retrospectively analyzed. Failed PatCap was assessed using ultrasonography combined with abdominal X-ray., Results: Among the eligible 250 patients, 129 retrieved the PatCap in their stool within 33 h after ingestion. Among the remaining 121 patients, abdominal X-ray was performed and the PatCaps were suspected to be in the small bowel in 57 patients. Among these 57 patients, abdominal ultrasonography identified 17 PatCaps in the small bowel. Among the selected 250 patients, 233 patients (93.2%) were eligible for capsule endoscopy examination, while 17 patients (6.8%) were not eligible. Capsule endoscopy passed through the small intestine without any incident., Conclusion: We confirmed that the abdominal ultrasonography with a radiographic targeting of the PatCap location is a reliable indicator to avoid the risk of capsule endoscopy retention or impaction and can be performed in most hospitals and clinics., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: We have previously revealed the clinical factors and genetic polymorphisms associated with gastrointestinal mucosal injury and bleeding, induced by low-dose aspirin (LDA). After performing genome-wide analysis of single nucleotide polymorphisms (SNPs) using the Drug Metabolizing Enzymes and Transporters (DMET) system among drug metabolism and transporter genes, certain SNPs were found to increase the risk for LDA-induced small bowel bleeding. The aim of this study was to identify the SNPs involved in LDA-induced small bowel bleeding., Subjects and Methods: Subjects were patients taking LDA, with small bowel bleeding diagnosed using capsule endoscopy. We investigated the clinical characteristics and the previously identified SNPs, that were examined by the DNA direct sequence method., Results: 56 patients with bleeding and 410 controls taking LDA were enrolled. The risk factors associated with small bowel bleeding included smoking, cerebrovascular diseases, chronic renal failure, non-steroidal anti-inflammatory drug (NSAID) or anticoagulants combination, and two SNPs (CYP4F11 20043G>A (D446N) rs1060463, GSTP1 313A>G rs1695). After propensity score matching, GSTP1 rs1695 was significantly associated with small bowel bleeding., Conclusion: The GSTP1 SNP may be a predictive marker for small bowel bleeding among patients taking LDA., Competing Interests: Declaration of Competing Interest None., (Copyright © 2021 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background: Esophageal cancer is a lethal malignancy with a poor prognosis. The incidence of esophageal adenocarcinoma, which develops from Barrett's esophagus (BE), has recently been increasing. In a previous study, we found that PDZK1 expression is higher in long segment BE compared to that in short-segment BE. However, the function of PDZK1 in the mucosa of BE is unclear., Aims: Clarify the role of PDZK1 in BE mucosa using PDZK1 overexpressed cells., Methods: Human adenocarcinoma-derived OE33 cells were used as a parental cell line and transfected to generate PDZK1 overexpressed OE33 cells (PC cells) or transfected with empty vector as control cells (NC cells). Cell growth of NC and PC cells in 10% fetal bovine serum was evaluated by cell counting. The effect of PDZK1 on proteasome inhibitor (PSI)-induced apoptosis was qualified by fluorescence microscopy and quantified by flow cytometry. Expression of apoptosis-related proteins was evaluated by western blotting., Results: There were no significant differences in cell growth between NC and PC cells. PSI significantly increased apoptosis in NC cells, but not in PC cells. In response to PSI, increased levels of cleaved-caspase3 and decreased pro-caspase3 levels were found in NC cells, but not in PC cells. In NC cells, PSI significantly decreased Bcl-2 expression without affecting Bax levels. In contrast, high expression of both Bcl-2 and Bax was observed in PC cells., Conclusion: Overexpression of PDZK1 protein induces an apoptosis-resistant phenotype in BE cells, which may be a potential therapeutic target.

Background: Despite a need for assessment of endoscopic submucosal dissection (ESD) skills in order to track progress and determine competence, there is no structured measure of assessing competency in ESD performance. The present study aims to develop and examine validity evidence for an assessment tool to evaluate the recorded performance of ESD for gastric neoplasms., Methods: The ESD video assessment tool (EVAT) was systematically developed by ESD experienced endoscopists. The EVAT consists of a 25-item global rating scale and 3-item checklist to assess competencies required to perform ESD. Five unedited videos were each evaluated by 2-blinded experienced ESD endoscopists to assess inter-rater reliability using intraclass correlation coefficients (ICC). Seventeen unedited videos in total were rated by 3 blinded experienced ESD endoscopists. Validity evidence for relationship to other variables was examined by comparing scores of inexperienced (fellows) and experienced endoscopists (attending staff), and by evaluating the relationship between the EVAT scores and ESD case experience. Internal consistency was evaluated using Cronbach's alpha., Results: The inter-rater reliability for the total score was high at 0.87 (95% confidence interval 0.11 to 0.99). The total score [median, interquartile range (IQR)] was significantly different between the inexperienced (71, 63-77) and experienced group (95, 91-97) (P = 0.005). The total scores demonstrated high correlation with the number of ESD cases (Spearman's ρ = 0.79, P < 0.01). The internal consistency was 0.97., Conclusions: This study provides preliminary validity evidence for the assessment of video-recorded ESD performances for gastric neoplasms using EVAT.

Background: Although there are papers reporting on the accuracy of colon capsule endoscopy (CCE) compared with colonoscopy (CS), there are few reports on the detection rates of significant lesions by endoscopy nurses. We previously reported no significant difference in the detection rates for small bowel capsule endoscopy (SBCE) images among two well-trained physicians and one expert nurse., Objective: To evaluate the reading time and detection rate of the significant lesions of CCE images among novice and trained expert endoscopy nurses and novice physicians., Methods: CCE videos of 20 consecutive patients who performed both CCE and CS with clinically significant localized lesions were selected. Two trained expert endoscopy nurses, untrained two novice physicians, and novice three endoscopy nurses reviewed CCE videos. The detection rate of the lesions and reading time were compared among the three groups and were evaluated by comparison between the first and the second 10 videos., Results: The median reading time was the shortest (19 min) in the trained expert endoscopy nurses and the longest (45 min) in the novice nurses. The number of thumbnails tended to be more in the trained expert endoscopy nurses in the first 10-video reading. Although the detection rates of small polyps (<5 mm) were significantly lower (46.5%, p =0.025) in the novice nurses compared to the others, they were improved (35.2% to 63.5%, p =0.015) in the second 10 videos. The detection rates of tumor lesions by either one of two trained expert endoscopy nurses were higher compared to those by each novice physician., Conclusions: The trained expert endoscopy nurses for CCE reading can reduce physician's time and improve the diagnostic yield., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2021 Yukiko Handa et al.)

Background: Barrett's esophagus (BE) is a predisposing factor for esophageal adenocarcinoma (EAC); however, the precise mechanism underlying this association remains unclear. The identification of biomarkers that are associated with an increased risk of BE progression to EAC would facilitate diagnosis and early treatment. Toward this goal, we aimed to identify biomarkers associated with BE and EAC in patients., Methods: In conjunction with high-resolution magnified endoscopy with narrow-band imaging (ME-NBI), we obtained brushing samples from the long-segment BE (LSBE) or short-segment BE (SSBE) of patients with EAC or without EAC (control). To identify candidate biomarker genes, microarray analysis was performed for a training set of 28 American samples. To confirm the microarray results, expression levels of the 16 candidate biomarkers were evaluated by real-time polymerase chain reaction analysis, using samples collected from an additional 53 American patients. In addition, we also performed a functional analysis for these genes using Gene Ontology (GO) enrichment analysis., Results: Among the 16 genes identified as differentially expressed by microarray analysis, the GO analysis indicated matrix metalloproteinase (MMP) family associated with 'collagen metabolic process' and 'multicellular organismal macromolecule metabolic process' as the two top biological processes. Brushing samples of patients with EAC showed up-regulated expression of decay-accelerating factors (DAF and CD55) and topoisomerase type Iiα (TOP2A), and down-regulated expression of the sodium channel epithelial 1 beta subunit (SCNN1B)., Conclusions: The up-regulation of CD55 and TOP2A, and the down-regulation of SCNN1B were common to the brushing samples and might serve as molecular biomarkers for identifying EAC in patients with SSBE., Trial Registration: University Hospital Medical Information Network (UMIN) (000004004).

Background: Although postoperative strictures after endoscopic submucosal dissection (ESD) in the rectum are relatively rare, some rectal lesions require resection involving the anal canal, which is a narrow tract comprising squamous epithelium. To the best of our knowledge, no studies have investigated narrow anal canals when evaluating post-ESD strictures. This study aimed to evaluate the impact of resections involving the anal canal on postoperative stricture development., Methods: Between April 2005 and October 2017, 707 rectal lesions were treated with ESD. We retrospectively investigated 102 lesions that required ≥ 75% circumferential resection. Risk factors for post-ESD stricture and, among patients with strictures, obstructive symptoms, and number of dilation therapies required were investigated., Results: Post-ESD stricture occurred in 18 of 102 patients (17.6%). In the multivariate analysis, circumferential resection ≥ 90% and ESD involving the anal canal (ESD-IAC) were risk factors for postoperative strictures (P ≤ 0.0001 and 0.0115, respectively). Among the patients with strictures, obstructive symptoms were significantly related to anal strictures compared to rectal strictures (100% vs. 27.2%, P = 0.0041). Furthermore, the number of dilation therapies required was significantly greater among patients with anal strictures compared to those with rectal strictures (6.5 times vs. 2.7 times, P = 0.0263)., Conclusion: Not only circumferential resection ≥ 90% but also ESD-IAC was a significant risk factor for the stricture after rectal ESD. Furthermore, anal strictures were associated with a significantly higher frequency of obstructive symptoms and larger number of required dilation therapies than were rectal strictures.

Background and study aims  Adequate mucosal elevation by submucosal injection is crucial for patient safety and efficiency during endoscopic submucosal dissection (ESD). This study aimed to evaluate the efficacy of fibrin glue (FG) as a long-lasting submucosal injection agent and to evaluate the technical feasibility of FG injection for ESD. Materials and methods  To compare the capabilities of different agents in maintaining submucosal evaluation, we injected FG, hyaluronic acid solution, and normal saline into the porcine gastric specimen that was incised into approximately 5 × 5 cm squares. Then, we measured the height of submucosal elevations over time. Moreover, three hypothetical lesions from the resected porcine stomach underwent ESD with FG injection. Thereafter, we conducted macroscopic and histopathologic analyses. Results FG maintained the greatest submucosal elevation among all the injection agents. Three ESD procedures were performed with en bloc resection. Both macroscopic and histopathologic findings showed a thick FG clot on the ulcers. Conclusions  The FG solution can be potentially used as an ESD submucosal injection agent in an in vitro model., Competing Interests: Competing interests The authors declare that they have no conflict of interest., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commecial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Background: Most studies on gut microbiome of irritable bowel syndrome (IBS) have focused on fecal microbiota, instead of mucosa-associated microbiota (MAM)., Aims: The aim of this study wasto investigate the MAM in IBS patients including the difference in subtypes of IBS, namely, diarrhea-predominant IBS (IBS-D) and constipation-predominant IBS (IBS-C)., Methods: Endoscopic brush samples were taken from terminal ileum and sigmoid colon of patients with IBS (17 IBS-D patients and 7 IBS-C patients) and 10 healthy controls. The MAM of samples was profiled by 16S rRNA gene amplicon sequencing. Potential changes in the MAM at the functional level were evaluated using PICRUSt software and the KEGG database., Results: There were no differences in MAM composition between terminal ileum and sigmoid colon according to β-diversity based on the UniFrac distance. In view of α-diversity, Shannon (evenness) but not Chao1 (richness) or observed operational taxonomic units tended to be lower in sigmoid colon MAM of IBS-C and IBS-D than the control group. The abundance of 4 genera in the sigmoid colon and 7 genera in the terminal ileum was significantly different among the 3 groups. Linear discriminant analysis effect size (LEfSe) showed that the genera of Ruminococcus, Akkermansia, Butyrivibrio, Methylobacterium, and Microbacterium and the family Erysipelotrichaceae were significantly higher in the IBS-C group, and the abundance of the genera Streptococcus, Acidaminococcus, Butyricicoccus, and Parvimonas was significantly higher in the IBS-D group. In addition, the proportion of genes responsible for the secretion system and LPS biosynthesis was significantly higher and that for methane metabolism, lysine biosynthesis, and enzyme families was significantly lower in the IBS-D group than in the IBS-C group., Conclusion: Dysbiosis pattern and the function of the microbiome seem to be different among subtypes of IBS, and MAM may play a crucial role in IBS symptom generation., (© 2020 S. Karger AG, Basel.)

Objective Antithrombotic drugs are being used increasingly frequently to prevent cardiovascular diseases. Few studies have evaluated small bowel mucosal injury induced by dual antiplatelet therapy (DAPT). The aim of the present study was to evaluate small bowel mucosal injury induced by DAPT compared with other antithrombotics using video capsule endoscopy (VCE). Methods The study included chronic users of antithrombotics who underwent VCE for obscure gastrointestinal bleeding between January 2007 and July 2018. We evaluated the instances of small bowel injury classified into erosions and ulcers. Results Overall, 183 patients (114 men and 69 women; mean age, 73.6 years old) were enrolled, and the study groups comprised 49 patients taking low-dose aspirin (LDA) only, 50 taking anticoagulants only, 37 being treated with DAPT, 33 on combined LDA and anticoagulants, and 14 taking P2Y12 inhibitors. Small bowel erosions and ulcers were most frequently observed in the DAPT group, with frequencies of 78.4% and 37.8%, respectively. Exacerbating factors of small bowel ulcers were DAPT [odds ratio (OR) 3.0, 95% confidence interval (CI) 1.2-7.7] and age over 80 years old (OR 2.4, 95% CI 1.1-5.4). Conclusion P2Y12 inhibitors seem to exacerbate LDA-induced small bowel injury. Preventive strategies for small bowel injury induced by LDA, especially DAPT, are urgently required.

Background/aims: Mucosal cutting biopsy (MCB) is useful for the histopathological diagnosis of gastric subepithelial tumors (SETs). However, there is little information on cases in which MCB did not establish a diagnosis. In the current study, we aimed to investigate the characteristics of cases in which MCB was unsuccessful., Methods: Cases in which MCB was used to histopathologically diagnose gastric SETs at Kobe University Hospital between August 2012 and October 2018 were retrospectively reviewed., Results: Forty-five cases in which MCB was used to diagnose 43 gastric SETs in 43 patients were analyzed. The median tumor size was 20 mm (range, 8-50 mm). Pathological examinations resulted in definitive and suspected diagnoses and no diagnosis in 29 (gastrointestinal stromal tumor: n=17, leiomyoma: n=7, aberrant pancreas: n=3, others: n=2), 6, and 10 cases, respectively. Failure to expose the tumor according to retrospective examinations of endoscopic images was significantly associated with no diagnosis. Other possible explanations included a less elevated tumor, biopsy of the surrounding field instead of the tumor due to the mobility, and poor endoscope maneuverability due to the tumor being close to the cardia., Conclusion: Clear exposure of gastric SETs during MCB may improve the diagnostic rate of such examinations.

Helicobacter pylori is a well-known bacterium that infects the human gastric mucosa and causes gastric inflammation, ultimately resulting in gastric cancer. To reduce the incidence of gastric cancer, eradication therapy is important. However, the rate of successful eradication gradually decreases due to increased antibiotic resistance to Helicobacter pylori . In order to increase the eradication rate and reduce gastric cancer incidence, food factors or probiotics are expected to play a beneficial role. Although several foods have been reported to inhibit bacterial load and gastric inflammation, further assessment on large population prospective studies in this field is warranted. Several food compounds, including phytochemicals, are reported to suppress the incidence of gastric cancer. Future evaluations should consider differences in geographic factors. Probiotics are effective and safe for use in Helicobacter pylori eradication therapy., Competing Interests: YN received a scholarship fund from EA Pharma. Co. Ltd. and collaboration research fund from FUJIFILM Medical Co. Ltd. and Taiyo Kagaku Co., Ltd., and has been paid lecture fees by Mylan EPD Co., Takeda Pharma. Co. Ltd., Mochida Pharma. Co. Ltd., EA Pharma. Co. Ltd., Otsuka Pharma. Co. Ltd., Nippon Kayaku Co. Ltd., and Miyarisan Pharma. Co. Ltd. The present research was partly funded by these funds. Neither the funding agency nor any outside organization has participated in study design or have any competing of interest. AS received a scholarship fund from Takeda Pharma. Co. Ltd., Mochida Pharma. Co. Ltd., and Daiichi-Sankyo Pharma. Co. Ltd. and collaboration research fund from AstraZeneca Co. Ltd. And has been paid lecture fees by Takeda Pharma. Co. Ltd., and Astellas Pharma. Co. Ltd. The present research was partly funded by these funds. Neither the funding agency nor any outside organization has participated in study design or have any competing of interest., (Copyright © 2020 JCBN.)

Background and Aim: Upper gastrointestinal symptoms (UGSs), including reflux and dyspeptic symptoms (postprandial distress syndrome [PDS] and epigastric pain syndrome [EPS]), affect health-related quality of life. However, the influence of sex on the relationship between body mass index (BMI) and UGSs remains controversial. This study investigates the influence of sex on this association in healthy subjects., Methods and Results: We utilized the database of a prospective, multicenter, cohort study of 7112 subjects who underwent upper endoscopy for health screening. A multivariable logistic regression analysis was conducted to assess the association between BMI and UGSs stratified by sex, adjusting for clinical features. The influence of sex on the association between the overlapping of UGSs and BMI in symptomatic subjects was also investigated. Reflux symptoms were significantly associated with high BMI (multivariable odds ratio [OR] 1.36; 95% confidence interval [CI] 1.10-1.67, P = 0.004). PDS symptoms were significantly associated with low BMI (OR 2.37; 95% CI 1.70-3.25; P  < 0.0001), but EPS symptoms were not associated with BMI. The association between reflux symptoms and higher BMI was limited to men (men: OR 1.40; 95% CI 1.10-1.77; P = 0.005, women: P = 0.40). sex did not influence the association between the presence of PDS symptoms and lower BMI. The percentage of overlapping of all three symptoms (reflux, PDS, and EPS) was higher in women than in men (19.9% [58/292] vs 10.5% [49/468], P = 0.0002)., Conclusions: The influence of BMI on the presence of UGSs was significantly different according to sex in this large-scale cohort., (© 2020 The Authors. JGH Open: An open access journal of gastroenterology and hepatology published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background and Aim: One of the main concerns related to peroral endoscopic myotomy (POEM) is postoperative gastroesophageal reflux (GER). The two penetrating vessels (TPVs) that are found at the boundary between the circular and oblique muscles in the posterior cardia wall have been suggested to be a good indicator of the optimal distal extent of POEM. However, the effect of performing myotomy using the TPVs as an anatomical reference on the frequency of post-POEM GER has not been studied., Methods: This study involved consecutive patients who underwent POEM for the treatment of achalasia between April 2015 and June 2017. All enrolled patients underwent POEM in the 5 o'clock position and were divided into two groups: the conventional line group (CL group, n = 31), in which the TPVs were not exposed during submucosal tunnel dissection in the cardia, and the TPVs line group (TPVs group, n = 83), in which the TPVs were exposed and gastric myotomy was performed along the right side of the TPVs to preserve the oblique muscle. Examinations for post-POEM GER were conducted 3 months after the POEM., Results: The frequency of grade B or higher reflex esophagitis was 26/83 (31.3%) in the TPVs group and 18/31 (58.1%) in the CL group (P = 0.017). Nine of 83 patients (10.8%) had GER symptoms in the TPVs group, and six of 31 (19.4%) had GER symptoms in the CL group (P = 0.23)., Conclusions: The novel myotomy method preserving oblique muscle using TPVs as anatomical landmarks significantly reduced the frequency of post-POEM GER., (© 2019 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Although treatment for esophageal motility disorder improves dysphagia and increases body weight, the effect of the treatment on body composition is unclear. This study aimed to assess the change in body composition between before and after treatment, the preoperative predictors of muscle increase, and the association between muscle increase and quality of life. Sixty-one patients (achalasia, n = 55; spastic esophageal disorder n = 6) who underwent per-oral endoscopic myotomy were analyzed in a single-arm prospective observational study. Appendicular skeletal muscle mass was measured with dual X-ray absorptiometry before and 3 months after per-oral endoscopic myotomy. For subgroup analysis, patients with postoperative appendicular skeletal muscle mass increase were defined as the muscle-increase group and the rest as the non-muscle-increase group. Preoperative factors related to the muscle-increase group were clarified via multivariate analysis. Further, the improvement after per-oral endoscopic myotomy in health-related quality-of-life score (Short Form-36) was compared between the muscle-increase and non-muscle-increase groups. Appendicular skeletal muscle mass increased significantly 3 months after per-oral endoscopic myotomy (P = 0.0002). The patients who underwent effective treatment (postoperative Eckardt score < 3) showed a significant improvement in appendicular skeletal muscle mass compared to those who did not (P = 0.04). In the stepwise logistic regression analysis, the preoperative Eckardt score (odds ratio: 1.95, 95% confidence interval 1.30-3.26, P = 0.0005) and preoperative serum prealbumin (odds ratio: 0.83, 95% confidence interval 0.70-0.97, P = 0.02) were identified as independent factors related to postoperative muscle increase. The improvements in the Short Form-36 domains of General Health (P = 0.0007) and Vitality (P = 0.003) were significantly higher in the muscle-increase group. The findings show that effective treatment improved the body composition of patients with esophageal motility disorder and that the Eckardt score and serum prealbumin may aid the prediction of increased appendicular skeletal muscle mass after treatment, resulting in a better quality of life., (© The Author(s) 2019. Published by Oxford University Press on behalf of International Society for Diseases of the Esophagus.)

Background and Study Aims: Gastrointestinal (GI) fistulas arise as adverse events of GI surgery and endoscopic treatment as well as secondary to underlying diseases, such as ulceration and pancreatitis. Until a decade ago, they were mainly treated surgically or conservatively. Bioabsorbable polyglycolic acid (PGA) sheets and fibrin glue, which are commonly used in surgical procedures, have also recently been used in endoscopic procedures for the closure of GI defects. However, there have only been few case reports about successful experiences with this approach. There have not been any case-series studies investigating the strengths and weaknesses of such PGA sheet-based treatment. In this study, we evaluated the clinical effectiveness of using PGA sheets to close GI fistulas., Patients and Methods: Cases in which patients underwent endoscopic filling with PGA sheets and fibrin glue for GI fistulas at Kobe University Hospital between January 2013 and April 2018 were retrospectively reviewed., Results: A total of 10 cases were enrolled. They included fistulas due to leakage after GI surgery, aortoesophageal/bronchoesophageal fistulas caused by chemoradiotherapy, or severe acute pancreatitis. The fistulas were successfully closed in 7 cases (70%). The unsuccessful cases involved a fistula due to leakage after surgical esophagectomy and bronchoesophageal fistulas due to chemoradiotherapy or severe acute pancreatitis. Unsuccessful treatment was related to fistula epithelization., Conclusion: Endoscopic plombage with PGA sheets and fibrin glue could be a promising therapeutic option for GI fistulas.

Background: Current methods for teaching and assessing competencies for endoscopic submucosal dissection (ESD) are highly variable, non-systematic, and are inefficient for the learner to acquire adequate skills. The present study aims to define and establish expert consensus regarding competencies required to perform ESD for gastric neoplasms., Methods: Fourteen ESD experts from 12 institutions in Japan were invited to complete an online survey to rate potential items for their importance in performing ESD proficiently. By using methodology based on the Delphi principles, the results of each round were analyzed and re-sent to the experts until consensus was established. Items were included if ranked 8 out of a 10-point Likert scale, by ≥ 80% of the respondents., Results: A list of 29 potential items was generated through a review of the literature, textbooks, and experience of the steering group members. Ten new items were added through the survey. Consensus was reached after three rounds. Response rate ranged from 93 to 100%. Thirty-four items achieved consensus as important surrogates of competency in performing ESD., Conclusions: Essential competencies for performing ESD were identified through expert consensus. These competencies can serve as the foundation for structured training and for development of objective assessment tools to evaluate trainee performance in ESD.

Background and study aims  Previously, we reported that esophageal muscle layer thickness was associated with technical complexity of peroral endoscopic myotomy (POEM). However, there are no data regarding the mid-term effects of POEM procedures on esophageal muscle layer thickness. Therefore, we conducted this study to elucidate mid-term effects of POEM procedures, and to examine whether postoperative changes in esophageal muscle layer thickness were related to particular clinico-pathological features in patients with esophageal motility disorders. Patients and methods  Seventy-four consecutive patients with esophageal motility disorders who underwent POEM at Kobe University Hospital from April 2015 to December 2016 were prospectively recruited into this study. First, we investigated the esophageal muscle layer thickness values obtained at 1 year after POEM. Second, we evaluated the effects of a reduction in muscle layer thickness on various clinico-pathological features. Results  At 1 year after POEM, mean thickness of the inner circular muscle at 0 cm, 5 cm, and 10 cm from the esophagogastric junction was 1.06 ± 0.45 mm, 0.99 ± 0.36 mm, and 0.97 ± 0.44 mm, respectively. Among all sites, muscle layer thickness had significantly decreased after POEM. However, univariate logistic regression analysis demonstrated that no clinical factors were associated with esophageal muscle layer thickness after POEM procedure. Conclusions  We demonstrated for the first time that thickness of the esophageal muscle layer was significantly decreased after POEM. This result reveals that changes in esophageal muscle layer thickness caused by esophageal motility disorders are reversible.

A 74-year-old female, who was diagnosed with superficial esophageal cancer, underwent endoscopic submucosal dissection (ESD) at another hospital, but a perforation occurred during the procedure. The perforation was closed with endoscopic clips, and the ESD was halted. The patient was referred to our hospital, and ESD was retried. There was severe fibrosis around the lesion, and injections into the submucosal layer were difficult. In addition, it was not possible to identify the submucosal layer, and making an oral-side incision caused a large perforation along the incision line. As continuing the submucosal dissection with an endoknife was considered difficult, the lesion was finally resected with hybrid ESD using a snare. The perforation was closed using polyglycolic acid (PGA) sheets and fibrin glue. Endoscopy performed 6 days later showed that the defect had been closed, and no contrast leakage was detected. Follow-up endoscopy conducted 3 months after the ESD showed ulcer healing at the dissection site and scar formation, but no residual tumor or esophageal stricture was noted. Our experience suggests that the use of PGA sheets with fibrin glue is a feasible, safe, and effective way of treating large esophageal perforations during ESD.