Impact of an artificial intelligence-aided endoscopic diagnosis system on improving endoscopy quality for trainees in colonoscopy: Prospective, randomized, multicenter study.

OBJECTIVE: This study was performed to evaluate whether the use of CAD EYE (Fujifilm, Tokyo, Japan) for colonoscopy improves colonoscopy quality in gastroenterology trainees. METHODS: The patients in this multicenter randomized controlled trial were divided into Group A (observation using CAD EYE) and Group B (standard observation). Six trainees performed colonoscopies using a back-to-back method in pairs with gastroenterology experts. The primary end-point was the trainees' adenoma detection rate (ADR), and the secondary end-points were the trainees' adenoma miss rate (AMR) and Assessment of Competency in Endoscopy (ACE) tool scores. Each trainee's learning curve was evaluated using a cumulative sum (CUSUM) control chart. RESULTS: We analyzed data for 231 patients (Group A, n = 113; Group B, n = 118). The ADR was not significantly different between the two groups. Group A had a significantly lower AMR (25.6% vs. 38.6%, P = 0.033) and number of missed adenomas per patient (0.5 vs. 0.9, P = 0.004) than Group B. Group A also had significantly higher ACE tool scores for pathology identification (2.26 vs. 2.07, P = 0.030) and interpretation and identification of pathology location (2.18 vs. 2.00, P = 0.038). For the CUSUM learning curve, Group A showed a trend toward a lower number of cases of missed multiple adenomas by the six trainees. CONCLUSION: CAD EYE did not improve ADR but decreased the AMR and improved the ability to accurately locate and identify colorectal adenomas. CAD EYE can be assumed to be beneficial for improving colonoscopy quality in gastroenterology trainees. TRIAL REGISTRATION: University Hospital Medical Information Network Clinical Trials Registry (UMIN000044031).

Utility and safety of the self-expandable metallic colonic stent in Japanese patients who received systemic chemotherapy or palliative treatment for obstructive primary advanced colorectal cancer: A retrospective single-center medical chart evaluation.

Background and Aim: The present study aimed to compare the utility and safety of the colonic self-expandable metallic stent between patients with obstructive primary colorectal cancer who underwent chemotherapy or palliative treatment care and patients bridging for surgery. Methods: The cases of 71 patients with colonic obstructive stenosis and in-dwelling stents who were hospitalized between May 2012 and April 2020 at Karatsu Red Cross Hospital were retrospectively analyzed. The patients were classified into three groups: bridging for curative surgery (group I), receiving systemic chemotherapy (group II-A), and receiving only palliative treatment (group II-B). Technical and clinical success rates and complication rates after stenting were evaluated. Results: No significant differences were observed in the technical (procedure) success rates (group I: 100%; group II, 97.6% [II-A: 100%; II-B: 95.8%]). The total clinical success rate was 85.9% (61/71) and did not vary significantly among the groups (group I: 82.8%; group II 88.0% [II-A: 83.3%; II-B: 91.6%]). No significant differences were observed in the early complication rates between groups I and II and in the late complication rates between groups II-A and II-B. Nutrition status, general condition, tumor staging, and 1-year survival were poorer in group II than in group I. Conclusion: The findings show that colonic stenting for malignant obstruction was performed successfully and safely both in patients who received systemic chemotherapy or palliative therapy and in patients bridging for curative surgery, regardless of risk status for malnutrition, poor general condition, cancer stage progression, and short survival.

Aberrant hypomethylation at imprinted differentially methylated regions is involved in biparental placental mesenchymal dysplasia.

BACKGROUND: Placental mesenchymal dysplasia (PMD) is a morphological abnormality resembling partial hydatidiform moles. It is often associated with androgenetic/biparental mosaicism (ABM) and complicated by Beckwith-Wiedemann syndrome (BWS), an imprinting disorder. These phenomena suggest an association between PMD and aberrant genomic imprinting, particularly of CDKN1C and IGF2. The existence of another type of PMD containing the biparental genome has been reported. However, the frequency and etiology of biparental PMD are not yet fully understood. RESULTS: We examined 44 placental specimens from 26 patients with PMD: 19 of these were macroscopically normal and 25 exhibited macroscopic PMD. Genotyping by DNA microarray or short tandem repeat analysis revealed that approximately 35% of the macroscopic PMD specimens could be classified as biparental, while the remainder were ABM. We performed a DNA methylation analysis using bisulfite pyrosequencing of 15 placenta-specific imprinted differentially methylated regions (DMRs) and 36 ubiquitous imprinted DMRs. As expected, most DMRs in the macroscopic PMD specimens with ABM exhibited the paternal epigenotype. Importantly, the biparental macroscopic PMD specimens exhibited frequent aberrant hypomethylation at seven of the placenta-specific DMRs. Allelic expression analysis using single-nucleotide polymorphisms revealed that five imprinted genes associated with these aberrantly hypomethylated DMRs were biallelically expressed. Frequent aberrant hypomethylation was observed at five ubiquitous DMRs, including GRB10 but not ICR2 or ICR1, which regulate the expression of CDKN1C and IGF2, respectively. Whole-exome sequencing performed on four biparental macroscopic PMD specimens did not reveal any pathological genetic abnormalities. Clinical and molecular analyses of babies born from pregnancies with PMD revealed four cases with BWS, each exhibiting different molecular characteristics, and those between BWS and PMD specimens were not always the same. CONCLUSION: These data clarify the prevalence of biparental PMD and ABM-PMD and strongly implicate hypomethylation of DMRs in the pathogenesis of biparental PMD, particularly placenta-specific DMRs and the ubiquitous GRB10, but not ICR2 or ICR1. Aberrant hypomethylation of DMRs was partial, indicating that it occurs after fertilization. PMD is an imprinting disorder, and it may be a missing link between imprinting disorders and placental disorders incompatible with life, such as complete hydatidiform moles and partial hydatidiform moles.

Efficacy of elobixibat as bowel preparation agent for colonoscopy: Prospective, randomized, multi-center study.

BACKGROUND AND AIM: Elobixibat is a novel ileal bile acid transporter inhibitor. This study aimed to compare the efficacy, tolerability, and safety of the combination of elobixibat and 1 L of polyethylene glycol formulation containing ascorbic acid (PEG-Asc) solution versus the combination of sodium picosulfate and 1-L PEG-Asc solution as bowel preparation for colonoscopy. METHODS: This multi-center, randomized, observer-blinded, non-inferiority study recruited 210 outpatients who were assigned to either the elobixibat plus 1-L PEG-Asc group (group A) or the sodium picosulfate plus 1-L PEG-Asc group (group B). The quality of the bowel cleansing level was assessed by the Boston Bowel Preparation Scale (BBPS) and compared the bowel cleansing level between the groups. Data regarding bowel preparation time, patients' tolerability, and adverse events were also analyzed. RESULTS: Data for 196 patients (99 in group A and 97 in group B) were analyzed finally. BBPS was comparable between group A and B (8.3 ± 0.9 vs. 8.3 ± 0.7; P = 0.88). Consequently, the adequate bowel preparation rate in groups A and B was 95.0% and 99.0%, respectively (-4.0%, 95% CI -9.3 to 1.5). Bowel preparation time in group A was similar to that in group B (348.2 ± 79.8 min vs. 330.8 ± 82.5 min; P = 0.13), whereas, sleep disturbance was significantly less frequent in group A than in group B (10.2% vs. 22.7%; P = 0.02). CONCLUSIONS: The combination of elobixibat and 1-L PEG-Asc can be considered an alternative bowel preparation for colonoscopy considering the equivalent bowel cleansing effect and less frequent sleep disturbance. The Japan Registry of Clinical Trials (jRCTs41180026).

Safety and Efficacy of the Noncessation Method of Antithrombotic Agents after Emergency Endoscopic Hemostasis in Patients with Nonvariceal Upper Gastrointestinal Bleeding: A Multicenter Pilot Study.

Background and Aims: The present study aimed to clarify the safety and efficacy of the noncessation method of antithrombotic agents after emergency endoscopic hemostasis in patients with nonvariceal upper gastrointestinal bleeding (UGIB). Methods: In this multicenter, prospective, pilot study, we performed emergency endoscopic hemostasis for nonvariceal UGIB in patients taking antithrombotic agents and resumed the medications without a cessation period (group A). The clinical characteristics, types of antithrombotic agents, UGIB etiology, treatment outcome, and adverse events were evaluated. We used propensity score matching to compare treatment outcomes and adverse events with our previous cohort (group B) in whom antithrombotic agents were transiently discontinued after emergency endoscopic hemostasis. Results: Forty-three consecutive patients were prospectively enrolled. The main antithrombotic agents were low-dose aspirin and direct oral anticoagulants; 11 patients (25.6%) were taking multiple antithrombotics. Peptic ulcers were the main cause of bleeding (95.4%). Endoscopic hemostasis was successful in all patients and the incidence of rebleeding within a month was 7.0%. Propensity score matching created 40 matched pairs. Endoscopic hemostasis was performed by soft coagulation significantly more frequently in group A than in group B (97.5% versus 60.0%, P < 0.001). Neither the rebleeding rate within a month nor thromboembolic event rate was different between the two groups. However, the mean duration of hospitalization was significantly shorter in group A than in group B (8.6 ± 5.2 d versus 14.4 ± 7.1 d, P < 0.001). Conclusions: Antithrombotic agents possibly can be continued after successful emergency endoscopic hemostasis for nonvariceal UGIB.

DNA methylation analysis of multiple imprinted DMRs in Sotos syndrome reveals IGF2-DMR0 as a DNA methylation-dependent, P0 promoter-specific enhancer.

Haploinsufficiency of NSD1, which dimethylates histone H3 lysine 36 (H3K36), causes Sotos syndrome (SoS), an overgrowth syndrome. DNMT3A and DNMT3B recognizes H3K36 trimethylation (H3K36me3) through PWWP domain to exert de novo DNA methyltransferase activity and establish imprinted differentially methylated regions (DMRs). Since decrease of H3K36me3 and genome-wide DNA hypomethylation in SoS were observed, hypomethylation of imprinted DMRs in SoS was suggested. We explored DNA methylation status of 28 imprinted DMRs in 31 SoS patients with NSD1 defect and found that hypomethylation of IGF2-DMR0 and IG-DMR in a substantial proportion of SoS patients. Luciferase assay revealed that IGF2-DMR0 enhanced transcription from the IGF2 P0 promoter but not the P3 and P4 promoters. Chromatin immunoprecipitation-quantitative PCR (ChIP-qPCR) revealed active enhancer histone modifications at IGF2-DMR0, with high enrichment of H3K4me1 and H3 lysine 27 acetylation (H3K27ac). CRISPR-Cas9 epigenome editing revealed that specifically induced hypomethylation at IGF2-DMR0 increased transcription from the P0 promoter but not the P3 and P4 promoters. NSD1 knockdown suggested that NSD1 targeted IGF2-DMR0; however, IGF2-DMR0 DNA methylation and IGF2 expression were unaltered. This study could elucidate the function of IGF2-DMR0 as a DNA methylation dependent, P0 promoter-specific enhancer. NSD1 may play a role in the establishment or maintenance of IGF2-DMR0 methylation during the postimplantation period.

Risk Factors for Post-Endoscopic Retrograde Pancreatography Pancreatitis: A Retrospective Chart Review in a Regional Hospital in Japan.

BACKGROUND: Endoscopic retrograde pancreatography (ERCP) is sometimes complicated by post-ERCP pancreatitis (PEP), which is a severe adverse effect. OBJECTIVE: The present study was performed to (i) evaluate the risk factors for PEP and (ii) compare the risk of PEP after ERCP performed in the off hours versus regular hours. METHODS: This retrospective study included 374 patients who underwent ERCP from January 2013 to December 2017. Among these patients, 38 (10.2%) developed PEP. The potential risk factors for PEP were evaluated by multivariate regression analysis, and the risk of PEP was compared between ERCP performed during regular hours and off hours. RESULTS: The independent risk factors for PEP were a relatively younger age (<75 years; p = 0.024), female sex (p = 0.002), a history of pancreatitis (p = 0.044), and performance of pancreatography (p = 0.010). Use of a diclofenac suppository and performance of pancreatic stenting were not preventive for PEP after ERCP. The complication rate of PEP did not differ between ERCP performed during the off hours versus regular hours. CONCLUSIONS: A relatively younger age (<75 years), female sex, a history of pancreatitis, and performance of pancreatography were potential risk factors for PEP, whereas the risk of PEP was not different between ERCP performed during the off hours versus regular hours.

An Investigation of Nine Patients with Gastrointestinal Immune-Related Adverse Events Caused by Immune Checkpoint Inhibitors.

INTRODUCTION/AIMS: Immune checkpoint inhibitors (ICIs) sometimes cause immune-related adverse events (irAEs), of which there is little information in the literatures. The objective of this study was to characterize the clinical features of gastrointestinal irAEs (GI irAEs). MATERIALS AND METHODS: From a total of 250 patients who were administered anti-PD-1 antibodies (nivolumab and pembrolizumab), we retrospectively identified 9 patients with grade 2 or higher GI irAE based on medical records. Patient characteristics, clinical features, imaging and pathological findings, and treatment course were evaluated. RESULTS: Grade 2 or higher GI irAEs were observed in 9 (3.6%) patients. Of the 9 patients who experienced GI irAE, 8 were male, and mean age was 63.2 years. Five patients received nivolumab and 4 received pembrolizumab. The GI irAEs observed were diarrhea in 7 patients and bloody stool in 2 patients. Grade 2 GI irAEs were identified in 3 patients and grade 3 GI irAEs in 6 patients. The average time from ICI administration to the onset of GI irAEs was 22.2 weeks (range 7-56 weeks) for nivolumab and 19.7 weeks (range 11-28 weeks) for pembrolizumab. Endoscopic findings showed ulcerative colitis-like findings in 3 of 7 patients, and pathological examination revealed crypt epithelial cell apoptosis in 6 of 7 patients. Eight of the 9 patients received steroids, and 2 patients received infliximab additionally. All GI irAEs were manageable. CONCLUSIONS: Because of the lack of specific clinical, imaging, and pathological findings, information of ICI use was indispensable for diagnosis. Although GI irAEs are controllable by steroid and infliximab, further studies regarding management strategy will be needed.

Correlation of Barrett's esophagus with colorectal polyps in Japanese patients: A retrospective chart review.

BACKGROUND AND AIM: Barrett's esophagus and colorectal polyps have several overlapping risk factors. Whereas several reports in Western countries have indicated a close relationship between Barrett's esophagus and colorectal polyps, the relationship between these two diseases remains unclear in Japan. This study was performed to determine whether the prevalence of Barrett's esophagus is related to that of colorectal polyps in Japanese patients. METHODS: The present retrospective chart review included 1582 Japanese patients who underwent both total colonoscopy and esophagogastroduodenoscopy from January 2010 to December 2016. The data on colorectal polyps and Barrett's esophagus were obtained from the endoscopic findings. The medical record of each patient was checked for age, sex, body mass index, smoking, alcohol drinking, use of acid suppression agents, and comorbidities including a history of diabetes, ischemic heart disease, gastroesophageal reflux disease, hiatal hernia, and Helicobacter pylori infection. RESULTS: Colorectal polyps were detected in 789 of the 1582 patients (49.9%). Barrett's esophagus was detected in 233 patients (14.7%), and most cases of Barrett's esophagus (n = 229) were classified as short-segment Barrett's esophagus. Colorectal polyps were more frequent in patients with than without Barrett's esophagus (odds ratio, 1.79; 95% confidence interval, 1.31-2.46; P < 0.001). In addition to Barrett's esophagus, the data indicated that old age, male sex, obesity, smoking, alcohol drinking, diabetes mellitus, and ischemic heart disease were independent risk factors for colorectal polyps. CONCLUSIONS: The present study revealed the correlation between the prevalence of Barrett's esophagus and colorectal polyps in Japanese patients.

Smoking and Drinking Did Not Increase the Failure of Therapeutic Helicobacter pylori Eradication by Vonoprazan, Clarithromycin, and Amoxicillin.

AIMS: The influence of lifestyle-related factors, including smoking and drinking, was evaluated for Helicobacter pylori eradication therapy with vonoprazan or proton pump inhibitors (PPIs). METHODS: Between 2012 and 2016, the medical records of 620 patients receiving H. pylori eradication therapy at Saiseikai Karatsu Hospital were evaluated. Patients had received vonoprazan (20 mg) or PPIs with 200 mg clarithromycin and 750 mg amoxicillin twice daily for 7 days. The influence of lifestyle-related factors on eradication failure was determined in the 2 groups. RESULTS: The eradication rates for vonoprazan and lansoprazole, rabeprazole, and esomeprazole were, respectively, 91.0, 73.8, 72.0, and 84.6%. The vonoprazan eradication rate was significantly higher than those for the PPIs (p < 0.01). Habitual smoking and drinking did not increase eradication failure, and smoking and drinking during the eradication period did not reduce the eradication rate. Metabolic syndrome-related factors including obesity, hypertension, and diabetes mellitus had no negative influence on the eradication rate. Eradication with vonoprazan was more effective compared with that achieved through the use of PPIs. CONCLUSION: Lifestyle-related factors including smoking and drinking did not exacerbate the H. pylori eradication failure, and vonoprazan was more effective than the PPIs.

Comprehensive methylation analysis of imprinting-associated differentially methylated regions in colorectal cancer.

BACKGROUND: Imprinted genes are regulated by DNA methylation at imprinting-associated differentially methylated regions (iDMRs). Abnormal expression of imprinted genes is implicated in imprinting disorders and tumors. In colorectal cancer (CRC), methylation and imprinting status of the IGF2/H19 domain have been studied. However, no comprehensive methylation analysis of iDMRs in CRC has been reported. Furthermore, the relationship between iDMR methylation status and other methylation-related issues, such as CpG island methylator phenotype (CIMP) and long interspersed element-1 (LINE-1) methylation, remains unclear. RESULTS: We analyzed the methylation status of 38 iDMRs in 106 CRC patients. We also investigated CIMP, LINE-1 methylation, KRAS and BRAF gene mutations, and loss of imprinting (LOI) of IGF2. We further examined the relationship between these factors and clinicopathological factors. The overall trend in iDMR methylation was towards hypermethylation, and iDMRs could be grouped into three categories: susceptible, resistant, and intermediate-to-aberrant methylation. The susceptible and resistant iDMRs consisted of all types of iDMR (gametic and somatic, maternally and paternally methylated). Hypermethylation of multiple iDMRs (HyMiD)-positive status was statistically associated with CIMP-positive status, but not associated with mutations in the BRAF and KRAS genes. HyMiD-positive status was inversely associated with LINE-1 methylation. Among four iDMRs within the IGF2/H19 domain, IGF2-DMR0 hypomethylation occurred most frequently, but was not associated with IGF2 LOI. Finally, we statistically calculated predictive prognostic scores based on aberrant methylation status of three iDMRs. CONCLUSION: In CRC tissues, some iDMRs were susceptible to hypermethylation independent of the type of iDMR and genomic sequence. Although HyMiD-positive status was associated with CIMP-positive status, this was independent of the BRAF and KRAS pathways, which are responsible for CIMP. Since IGF2-DMR0 hypomethylation and aberrant methylation of other iDMRs within the IGF2/H19 domain were not associated with IGF2 LOI, dysfunction of any of the molecular components related to imprinting regulation may be involved in IGF2 LOI. The prognostic score calculated based on aberrant methylation of three iDMRs has potential clinical applications as a prognostic predictor in patients. Further study is required to understand the biological significance of, and mechanisms behind, aberrant methylation of iDMRs and IGF2 LOI in CRCs.

Risk Factors for Helicobacter pylori Infection and Endoscopic Reflux Esophagitis in Healthy Young Japanese Volunteers.

Objective The aim of this study was to determine the prevalence and risk factors of reflux esophagitis and Helicobacter pylori (H.pylori) infection and their interrelationship in healthy young Japanese volunteers. Methods Between 2010 and 2016, 550 fifth-year medical students at Saga Medical School, aged 22 to 30 years, underwent upper gastrointestinal endoscopy and completed a questionnaire (frequency scale for symptoms of gastroesophageal reflux disease). H. pylori infection was determined by detecting urinary immunoglobulin G antibodies. Results H. pylori antibodies were detected in 45 of the 550 subjects (8.2%). Endoscopic reflux esophagitis was detected in 38 out of 550 (6.9%): grade A in 37 subjects (97.3%) and grade B in 1. Most subjects with reflux esophagitis were H. pylori-negative (35/37). Nodular gastritis was observed in 33.3% (15/45) of H. pylori-positive subjects. The risk factors for H. pylori infection were drinking well water in childhood, nodular gastritis, and duodenal ulcer scars. The risk factors for endoscopic reflux esophagitis were male gender and obesity (body mass index ≥25). Conclusion This study describes the risk factors for H. pylori infection and reflux esophagitis in healthy young Japanese subjects. The prevalence of reflux esophagitis was relatively high, and the infection rate of H. pylori was low compared with the aged Japanese population.

Increase in Endoscopic and Laparoscopic Surgery Regarding the Therapeutic Approach of Gastric Cancer Detected by Cancer Screening in Saga Prefecture, Japan.

Objective Despite recent advances in endoscopic treatment and laparoscopic surgery for gastric cancers, an increase in the uptake of these therapeutic approaches has not yet been fully demonstrated. Therefore, the present study aimed to investigate the change in therapeutic approaches regarding the treatment of gastric cancers detected by cancer screening in Saga Prefecture, Japan between April 2002 and March 2011. Methods Gastric cancer screening by X-ray was performed on 311,074 subjects between April 2002 and March 2011. In total, 534 patients were thereafter diagnosed with gastric cancer. Eighteen subjects were excluded because precise details of their treatment were not available. To evaluate the changes in the therapeutic approach, the observation period was divided into three 3-year intervals: Period I: April 2002 to March 2005; Period II: April 2005 to March 2008; Period III: April 2008 to March 2011. Results The use of open laparotomy for the treatment of gastric cancer decreased, and laparoscopic surgery and endoscopic treatment increased markedly in a time-dependent manner. A 2.5-fold increase in endoscopic treatment, and a 18.4-fold increase in laparoscopic surgery were observed in Period III compared with Period I (after adjusting for age and tumor characteristics). Conclusion Endoscopic treatment and laparoscopic surgery for gastric cancer increased during the investigation period (2002-2011), although the tumor characteristics of the gastric cancers detected through cancer screening in Saga Prefecture, Japan did not show any changes.

Upper Gastrointestinal Symptoms Are More Frequent in Female than Male Young Healthy Japanese Volunteers as Evaluated by Questionnaire.

BACKGROUND/AIMS: Upper gastrointestinal symptoms are more frequent and severe in female than in male outpatients in Japan. This study compared theupper gastrointestinal symptoms between healthy male and female young adult volunteers using a questionnaire. METHODS: In total, 581 third-grade medical students at Saga Medical School aged 22 to 30 years underwent upper gastrointestinal endoscopyand completed a questionnaire (frequency scale for symptoms of gastroesophageal reflux disease) from 2007 to 2013. Of these 581students, 298 who were negative for Helicobacter pylori infection and had no particular lesions on endoscopic examination wereenrolled in the present evaluation. A symptom was defined as positive when the subject evaluated the frequency of the symptom assometimes, often, or always. RESULTS: The subjects comprised of 163 males (average age, 23.7 years) and 135 females (average age, 23.1 years). Upper gastrointestinalsymptoms were more frequent in the females (75 of 135, 55.6%) than males (69 of 163, 42.3%; P < 0.05), with a high score for 4symptoms (bloated stomach, heavy feeling in the stomach after meals, subconscious rubbing of the chest with the hand, and feeling of fullness while eating meals). Of the 144 subjects (69 males and 75 females) who complained of these symptoms, the females complained of dysmotility symptoms more often than did the males, but this was not true for reflux symptoms. CONCLUSIONS: This study suggests that females develop upper gastrointestinal symptoms more frequently than do males among the young healthyJapanese population.

Perforation and postoperative bleeding of endoscopic submucosal dissection in gastric tumors: analysis of 1190 lesions in low- and high-volume centers in Saga, Japan.

BACKGROUND: This retrospective study aimed to determine risk factors associated with serious complications of endoscopic submucosal dissection of gastric tumors in multicenters compared between high- and low-volume centers. METHODS: Between 2001 and 2010, gastric endoscopic submucosal dissection was performed in 1190 lesions of 1082 patients in five hospitals in Saga, three high-volume and two low-volume centers. Risk factors for serious complications were evaluated. Patients' background characteristics were evaluated, including anticoagulants use and underlying diseases. RESULTS: Postoperative bleeding was detected in 75 patients (6.9%), and perforation was detected in 40 patients (3.7%). Most postoperative bleeding and perforation cases were recovered with endoscopic procedures, although one case of each complication was treated by emergency surgery. Multivariate analysis indicated that risk factors for perforation were tumor location, massive submucusal invasion, endoscopists' experience of 100-149 cases and hypertension, and that risk factors for postoperative bleeding were tumor location, resected tumor size, and scar lesion. The serious complications were not different between high- and low-volume centers. CONCLUSIONS: The present study indicated that risk factors for perforation during endoscopic submucosal dissection were tumor, endoscopist and patient related, although risk factors for postoperative bleeding were tumor related. There was no difference in complications between high- and low-volume centers.