Endoscopic features of synchronous multiple early gastric cancers: Findings from a nationwide cohort.

INTRODUCTION: We investigated the factors associated with synchronous multiple early gastric cancers and determined their localization. METHODS: We analyzed 8191 patients who underwent endoscopic submucosal dissection for early gastric cancers at 33 hospitals in Japan from November 2013 to October 2016. Background factors were compared between single-lesion (n=7221) and synchronous multi-lesion cases (n=970) using univariate and multivariate analyses. We extracted cases with two synchronous lesions (n=832) and evaluated their localization. RESULTS: Significant independent risk factors for synchronous multiple early gastric cancer were older age (≥75 years old) (OR=1.257), male sex (OR=1.385), severe mucosal atrophy (OR=1.400), tumor localization in the middle (OR=1.362) or lower region (OR=1.404), and submucosal invasion (OR=1.528 (SM1), 1.488 (SM2)). Depressed macroscopic type (OR=0.679) and pure undifferentiated histology OR=0.334) were more common in single early gastric cancers. When one lesion was in the upper region, the other was more frequently located in the lesser curvature of the middle region. When one lesion was in the middle region, the other was more frequently located in the middle region or the lesser curvature of the lower region. When one lesion was in the lower region, the other was more frequently located in the lesser curvature of the middle region or the lower region. CONCLUSION: Factors associated with synchronous multiple early gastric cancer included older age, male sex, severe mucosal atrophy, tumor localization in the middle or lower region, and tumor submucosal invasion. Our findings provide useful information regarding specific areas that should be examined carefully when one lesion is detected.

Multicenter study of invasive gastric cancer detected after 10 years of Helicobacter pylori eradication in Japan: Clinical, endoscopic, and histopathologic characteristics.

Objectives: Gastric cancer can be diagnosed even in patients long after Helicobacter pylori eradication. Most cases involve intramucosal lesions; however, some are invasive and require surgery. To clarify appropriate long-term surveillance methods, this study compared invasive gastric cancer diagnosed ≥10 and <10 years after eradication. Methods: This retrospective multicenter study included 14 institutions. We included 377 patients with gastric cancer with submucosal or deep invasion after surgical or endoscopic resection. Ordered logistic regression analysis was used to explore the factors contributing to the pathological stage and histological type. Results: Invasive gastric cancer was detected in 84 patients (Group L) and 293 patients (Group S) ≥10 and <10 years after H. pylori eradication, respectively. Endoscopic mucosal atrophy at the time of cancer detection was similar in both groups; 50% of the patients had severe atrophy. Annual endoscopy correlated with early pathological stage (odds ratio [OR] 0.28, 95% confidence interval [CI] 0.14-0.54, p < 0.001). Group L exhibited an independent correlation with the advanced pathological stage (OR 2.27, 95% CI 1.06-4.88, p = 0.035) and the undifferentiated type (OR 2.12, 95% CI 1.16-3.90, p = 0.015). The pure differentiated type and early pathological stage significantly (p = 0.001) correlated with severe mucosal atrophy in Group S but not in Group L. Conclusions: Invasive cancers diagnosed ≥10 years after H. pylori eradication were likely to be more malignant in histological type and pathological stage. Gastric cancer surveillance should continue regardless of endoscopic atrophy, particularly ≥10 years after eradication.

Current Status of Diagnosis and Treatment of Colorectal Cancer in Asian Countries: A Questionnaire Survey.

INTRODUCTION: Diagnostic and therapeutic methods for colorectal cancer (CRC) have advanced; however, they may be inaccessible worldwide, and their widespread use is challenging. This questionnaire survey investigates the current status of diagnosis and treatment of early-stage CRC in Asian countries. METHODS: Responses to the questionnaire were obtained from 213 doctors at different institutions in 8 countries and regions. The questionnaire consisted of 39 questions on the following four topics: noninvasive diagnosis other than endoscopy (6 questions), diagnosis by magnification and image-enhanced endoscopy (IEE) including artificial intelligence (AI) (10 questions), endoscopic submucosal dissection (ESD), proper use among other therapeutic methods (11 questions), and pathologic diagnosis and surveillance (12 questions). RESULTS: Although 101 of 213 respondents were affiliated with academic hospitals, there were disparities among countries and regions in the dissemination of advanced technologies, such as IEE, AI, and ESD. The NICE classification is widely used for the diagnosis of colorectal tumors using IEE, while the JNET classification with magnification was used in countries such as Japan (65/70, 92.9%) and China (16/22, 72.7%). Of the 211 respondents, 208 (98.6%) assumed that en bloc resection should be achieved for carcinomas, and 180 of 212 (84.9%) believed that ESD was the most suitable in cases with a diameter larger than 2 cm. However, colorectal ESD is not widespread in countries such as Thailand, the Philippines, and Indonesia. CONCLUSION: The promotion of advanced technologies and education should be continual to enable more people to benefit from them.

Association of direct oral anticoagulant and delayed bleeding with pharmacokinetics after endoscopic submucosal dissection.

BACKGROUND AND AIMS: Pharmacokinetic parameters, such as drug plasma level at trough, time to maximum plasma concentration (Tmax), and coagulation factor Xa (FXa) activity generally predict factors for the anticoagulant effects of direct oral anticoagulants (DOACs). Although GI bleeding is a major adverse event after endoscopic submucosal dissection (ESD), little is known about the association between post-ESD bleeding in patients taking DOACs and the pharmacologic parameters. This study aimed to evaluate pharmacologic risk factors for post-ESD bleeding in patients taking DOACs. METHODS: We prospectively evaluated the incidence of post-ESD bleeding in patients taking DOACs between April 2018 and May 2022 at 21 Japanese institutions and investigated the association with post-ESD bleeding and pharmacologic factors, including plasma concentration and FXa activity at trough and Tmax. RESULTS: The incidence of post-ESD bleeding was 12.8% (14 of 109; 95% confidence interval [CI], 7.2-20.6). Although plasma DOAC concentration and plasma level/dose ratio at trough and Tmax varied widely among individuals, a significant correlation with plasma concentration and FXa activity was observed (apixaban: correlation coefficient, -0.893; P < .001). On multivariate analysis, risk factors for post-ESD bleeding in patients taking DOACs were higher age (odds ratio [OR], 1.192; 95% CI, 1.020-1.392; P = .027) and high anticoagulant ability analyzed by FXa activity at trough and Tmax (OR, 6.056; 95% CI, 1.094-33.529; P = .039). CONCLUSIONS: The incidence of post-ESD bleeding in patients taking DOACs was high, especially in older patients and with high anticoagulant effects of DOACs. Measurement of pharmacokinetic parameters of DOACs may be useful in identifying patients at higher risk of post-ESD bleeding.

Factors associated with long-term efficacy of lubiprostone for chronic constipation.

The prevalence of chronic constipation in Japan is increasing, and is presently almost 1 in 5 people. Because constipation is common, especially in older patients, to avoid adverse events and polypharmacy, simple treatments at low doses are generally desired. Although the chloride channel activator lubiprostone is candidate drug that may solve these problems, factors associated with the long-term efficacy of lubiprostone monotherapy for chronic constipation in treatment-naive patients remain unclear. We here retrospectively investigated the clinical characteristics and factors of patients who achieved long-term constipation improvement with lubiprostone monotherapy. Seventy-four patients with chronic constipation treated with lubiprostone monotherapy (24 or 48 µg/day) from January 2017 to August 2018 were reviewed. Patient characteristics and clinical time-courses were compared between those who sustained improvement for 6 months, and those who became refractory to treatment. In 54 patients (76.1%), constipation improved by lubiprostone administration for 6 months. On multivariate analysis, a significant clinical factor associated with sustained improvement was a starting lubiprostone dose of 24 µg/day (odds ratio: 5.791; 95% confidence interval: 1.032-32.498; p = 0.046). A starting lubiprostone dose of 24 µg/day has efficacy to improve chronic constipation and to prevent adverse events of nausea and diarrhea in Japanese patients.

Significance of rescue hybrid endoscopic submucosal dissection in difficult colorectal cases.

BACKGROUND/AIMS: Hybrid endoscopic submucosal dissection (ESD), in which an incision is made around a lesion and snaring is performed after submucosal dissection, has some advantages in colorectal surgery, including shorter procedure time and preventing perforation. However, its value for rescue resection in difficult colorectal ESD cases remains unclear. This study evaluated the utility of rescue hybrid ESD (RH-ESD). METHODS: We divided 364 colorectal ESD procedures into the conventional ESD group (C-ESD, n=260), scheduled hybrid ESD group (SH-ESD, n=69), and RH-ESD group (n=35) and compared their clinical outcomes. RESULTS: Resection time was significantly shorter in the following order: RH-ESD (149 [90-197] minutes) >C-ESD (90 [60-140] minutes) >SH-ESD (52 [29-80] minutes). The en bloc resection rate increased significantly in the following order: RH-ESD (48.6%), SH-ESD (78.3%), and C-ESD (97.7%). An analysis of factors related to piecemeal resection of RH-ESD revealed that the submucosal dissection rate was significantly lower in the piecemeal resection group (25% [20%-30%]) than in the en bloc resection group (40% [20%-60%]). CONCLUSION: RH-ESD was ineffective in terms of curative resection because of the low en bloc resection rate, but was useful for avoiding surgery.

Assessment of delayed bleeding after endoscopic submucosal dissection of early-stage gastrointestinal tumors in patients receiving direct oral anticoagulants.

Delayed bleeding is a major and serious adverse event of endoscopic submucosal dissection (ESD) for early-stage gastrointestinal tumors. The rate of post-ESD bleeding for gastric cancer is higher (around 5%-8%) than that for esophagus, duodenum and colon cancer (around 2%-4%). Although investigations into the risk factors for post-ESD bleeding have identified several procedure-, lesion-, physician- and patient-related factors, use of antithrombotic drugs, especially anticoagulants [direct oral anticoagulants (DOACs) and warfarin], is thought to be the biggest risk factor for post-ESD bleeding. In fact, the post-ESD bleeding rate in patients receiving DOACs is 8.7%-20.8%, which is higher than that in patients not receiving anticoagulants. However, because clinical guidelines for management of ESD in patients receiving DOACs differ among countries, it is necessary for endoscopists to identify ways to prevent post-ESD delayed bleeding in clinical practice. Given that the pharmacokinetics (e.g., plasma DOAC level at both trough and Tmax) and pharmacodynamics (e.g., anti-factor Xa activity) of DOACs are related to risk of major bleeding, plasma DOAC level and anti-FXa activity may be useful parameters for monitoring the anti-coagulate effect and identifying DOAC patients at higher risk of post-ESD bleeding.

Underwater endoscopic submucosal dissection for colorectal tumors decreases the incidence of post-electrocoagulation syndrome.

BACKGROUND AND AIMS: Underwater endoscopic submucosal dissection (U-ESD) is a recently developed procedure that has the potential to prevent post-ESD coagulation syndrome (PECS) owing to its heat-sink effect. We aimed to clarify whether U-ESD decreases the incidence of PECS compared with conventional ESD (C-ESD). METHODS: A total of 205 patients who underwent colorectal ESD (C-ESD: 125; U-ESD: 80) were analyzed. Propensity score matching analysis was performed to adjust for patient backgrounds. Ten C-ESD and two U-ESD patients with muscle damage or perforation during ESD were excluded when comparing PECS. The primary outcome was to compare the incidence of PECS between the U-ESD and C-ESD groups (54 matched pairs). Secondary outcomes were to compare procedural outcomes between the C-ESD and U-ESD groups (62 matched pairs). RESULTS: Among the 78 patients who underwent U-ESD, PECS occurred in only one patient (1.3%). Adjusted comparisons between the U-ESD and C-ESD groups demonstrated a significantly lower incidence of PECS in the U-ESD group (0% vs 11.1%; P = 0.027). Median dissection speed was significantly faster in the U-ESD than in the C-ESD group (10.9 mm2 /min vs 6.9 mm2 /min; P < 0.001). En bloc and complete resection rates were 100% in the U-ESD group. Although perforation and delayed bleeding occurred in one patient each (1.6%) as adverse events in the U-ESD group, there were no differences compared with the C-ESD group. CONCLUSIONS: Our study demonstrates that U-ESD effectively decreases the incidence of PECS and is a faster and safer method for colorectal ESD.

Gastric squamous metaplasia observed by image-enhanced endoscopy.

A 61-year-old Helicobacter pylori-positive female with gastroesophageal reflux disease has undergone surveillance endoscopy every year for 13 years at Tokyo Medical University Hospital. At the first surveillance in 2009, conventional white light endoscopy showed a 10-mm whitish slightly depressed lesion at the lesser curvature of the gastric cardia. This lesion gradually increased in size to 15 mm over the 13-year observational period. Indigo carmine chromoendoscopy, narrow band imaging, and texture and color enhancement imaging in both mode 1 and mode 2 clearly emphasized the presence of a depressed whitish mucosa around the gastric mucosa compared with white light imaging. None of the three image-enhanced endoscopy techniques showed any abnormality in the vascular or structural pattern. Pathological findings showed squamous epithelium without atypia and revealed no evidence of malignancy in the stomach. We thus report a case of gastric squamous metaplasia without gastric neoplastic lesion in the gastric cardia whose lesions were endoscopically observed to change the size for more than 10 years and whose lesions were endoscopically evaluated with a texture and color enhancement imaging mode 1 and mode 2 and narrow band imaging.

Visibility of early gastric cancers by texture and color enhancement imaging using a high-definition ultrathin transnasal endoscope.

We evaluated whether texture and color enhancement imaging (TXI) using a high-definition ultrathin transnasal endoscope (UTE) improves the visibility of early gastric cancer (EGC) compared with white-light imaging (WLI). This study included 31 EGCs observed by TXI mode 2 using a high-definition UTE prior to endoscopic submucosal dissection. The first outcome was to compare the color differences based on Commission Internationale de l'Eclairage L*a*b* color space between EGCs and the surrounding mucosa by WLI and TXI using the UTE (objective appearance of EGC). The second outcome was to assess the visibility of EGCs by WLI and TXI using the UTE in an image evaluation test performed on 10 endoscopists (subjective appearance of EGC). Color differences between EGCs and non-neoplastic mucosa were significantly higher in TXI than in WLI in all EGCs (TXI: 16.0 ± 10.1 vs. WLI: 10.2 ± 5.5 [mean ± standard deviation], P < 0.001). Median visibility scores evaluated by 10 endoscopists using TXI were significantly higher than those evaluated using WLI (TXI: 4 [interquartile range, 4-4] vs. WLI: 4 [interquartile range, 3-4], P < 0.001). TXI using high-definition UTE improved both objective and subjective visibility of EGCs compared with WLI.

Association between perioperative management of antiplatelet agents and risk of post-endoscopic submucosal dissection bleeding in early gastric cancer: analysis of a nationwide multicenter study.

BACKGROUND AND AIMS: Data are lacking regarding post-endoscopic submucosal dissection (ESD) bleeding in patients with early gastric cancer (EGC) who take antiplatelet agents (APAs), particularly in those taking thienopyridine and cilostazol. We aimed to clarify the association between the status of APA medication and post-ESD bleeding risk. METHODS: This study is a secondary analysis using data from a recently conducted nationwide multicenter study in Japan. We retrospectively reviewed patients treated with APAs or on no antithrombotic therapy recruited from 33 institutions who underwent ESD for EGC between November 2013 and October 2016. The primary outcome of this study was the relationship between the rate of post-ESD bleeding and the status of each APA medication. RESULTS: A total of 9736 patients were included in the analysis. Among 665 aspirin users, the continuation group was significantly associated with post-ESD bleeding (odds ratio [OR], 2.79; 95% confidence interval [CI], 1.77-4.37). Among 227 thienopyridine users, the aspirin or cilostazol replacement group was not significantly associated with post-ESD bleeding (OR, 1.85; 95% CI, .72-4.78). Among 158 cilostazol users, there was no significant association with post-ESD bleeding, irrespective of medication status. The rate of post-ESD bleeding was approximately 10% to 20% irrespective of the status of APA administration among dual-antiplatelet therapy users. No patients experienced thromboembolic events in this study. CONCLUSIONS: Replacement of thienopyridine with aspirin or cilostazol may be acceptable for minimizing both the risk of post-ESD bleeding and thromboembolism in patients with EGC. In patients on cilostazol monotherapy undergoing ESD, continuation of therapy may be acceptable.

Prediction of depth of invasion and lymph node metastasis in superficial pharyngeal cancer by magnifying endoscopy using the Japan Esophageal Society classification.

Backgrounds: The pharynx has no muscularis mucosae, so it is unclear whether diagnostic techniques used for the esophagus can be applied to the pharynx. This study investigated the usefulness of magnifying endoscopy with narrowband imaging using the Japan Esophageal Society (JES) classification for predicting the depth of invasion and lymph node metastasis (LNM) in pharyngeal cancer. Methods: A total of 123 superficial pharyngeal carcinoma lesions that had been observed preoperatively with magnifying endoscopy with narrowband imaging between January 2014 and June 2021 were analyzed. Predictors of subepithelial invasion (SEP) and LNM were sought based on endoscopic findings, including microvascular morphology, using the JES classification. Results: The lesions were divided into carcinoma in situ (n = 41) and SEP (n = 82). Multivariate analysis identified B2-B3 vessels (odds ratio [OR] 6.54, 95% confidence interval [CI] 1.74-24.61, p = 0.005) and a middle/large avascular area (OR 4.15, 95% CI 1.18-14.62, p = 0.027) as independent predictors of SEP. Significant predictors of LNM were protruding type, B2-B3 vessels, middle/large avascular area, SEP, venous invasion, lymphatic invasion, and tumor thickness > 1000 µm. Median tumor thickness increased significantly in the order of B1 < B2 < B3 vessels (B1, 305 µm; B2, 1045 µm; B3, 4043 µm; p < 0.001). The LNM rates for B1, B2, and B3 vessels were 1.6% (1/63), 4.8% (2/42), and 55.6% (10/18), respectively (p < 0.001). Conclusions: Magnifying endoscopy with narrowband imaging using the JES classification could predict the depth of invasion in superficial pharyngeal carcinoma. The JES classification may contribute to the prediction of LNM, suggesting that it could serve as an alternative to tumor thickness.

Improvement of dyspeptic symptoms after Helicobacter pylori eradication therapy in Japanese patients.

Background and Aim: Helicobacter pylori eradication therapy effectively improves the abdominal symptoms and bowel habits of patients. Patients in whom dyspepsia is under control by 6 to 12 months after successful H. pylori eradication are defined as having H. pylori-associated dyspepsia, and patients with dyspepsia that is refractory to successful eradication are defined as having functional dyspepsia. Here, we aimed to investigate the association between H. pylori eradication and improvement of dyspepsia in the short and long term after eradication therapy. Methods: Dyspeptic symptoms before treatment and at 2 and 12 months after eradication were evaluated using the Gastrointestinal Symptom Rating Scale (GSRS) in 282 H. pylori-positive Japanese patients who underwent eradication therapy. Results: Of the Japanese H. pylori-positive patients, 48.2% (136/282) had upper abdominal symptoms. Eradication improved dyspepsia in 34.5% (47/136) of the patients at 2 months post eradication, which continued to be under control up to 12 months. A significant decrease at 2 and 12 months after eradication, compared with before eradication, was observed in total GSRS (from 25.7 ± 10.4 [before eradication, n = 249] to 23.3 ± 7.2 [after 2 months, n = 249] and 24.8 ± 7.8 [after 12 months, n = 81]; P = 0.014 and 0.321, respectively), gastric pain score (from 4.1 ± 1.9 to 3.7 ± 1.3 and 3.7 ± 1.2; P = 0.025 and 0.047), and constipation score (from 5.9 ± 3.1 to 5.2 ± 2.3 and 5.9 ± 3.0; P < 0.021 and 0.862). Conclusion: H. pylori-positive dyspepsia patients should be recommended to undergo H. pylori eradication to alleviate dyspepsia-associated symptoms.

Third-Generation High-Vision Ultrathin Endoscopy Using Texture and Color Enhancement Imaging and Narrow-Band Imaging to Evaluate Barrett's Esophagus.

It remains unclear whether texture- and color-enhancement imaging (TXI) and narrow-band imaging (NBI) provide an advantage over white-light imaging (WLI) in Barrett's esophagus. We compared endoscopic findings and color differences between WLI and image-enhanced endoscopy (IEE) using a third-generation ultrathin endoscope. We retrospectively enrolled 40 patients who evaluated Barrett's esophagus using WLI, TXI, and NBI. Color differences determined using the International Commission on Illumination 1976 (L∗, a∗, b∗) color space among Barrett's epithelium, esophageal, and gastric mucosa were compared among the endoscopic findings. As the secondary outcome, we assessed the subjective visibility score among three kinds of endoscopic findings. The prevalence of Barrett's esophagus and gastroesophageal reflux disease (GERD) in WLI was 82.5% and 47.5%, respectively, and similar among WLI, TXI, and NBI. Color differences between Barrett's epithelium and esophageal or gastric mucosa on NBI were significantly greater than on WLI (all p < 0.05). However, the color difference between Barrett's epithelium and esophageal mucosa was significantly greater on NBI than TXI (p < 0.001), and the visibility score of Barrett's epithelium detection was significantly greater on TXI than NBI (p = 0.022), and WLI (p = 0.016). High-vision, third-generation ultrathin endoscopy using NBI and TXI is useful for evaluating Barrett's epithelium and GERD compared with WLI alone.

Using texture and colour enhancement imaging to evaluate gastrointestinal diseases in clinical practice: a review.

White light imaging (WLI) is the most common endoscopic technique used for screening of gastrointestinal diseases. However, despite the advent of a new processor that offers sufficient clear illumination and other advanced developments in endoscopic instrumentation, WLI alone is inadequate for detecting all gastrointestinal diseases with abnormalities in mucosal discoloration and morphological changes to the mucosal surface. The recent development of image-enhanced endoscopy (IEE) has dramatically improved the detection of gastrointestinal diseases. Texture and colour enhancement imaging (TXI) is a new type of IEE that enhances brightness, surface irregularities, such as elevations or depressions, and subtle colour changes. TXI with two modes, namely modes 1 and 2, can selectively enhance brightness in dark areas of an endoscopic image and subtle tissue differences such as slight morphological or colour changes while simultaneously preventing over-enhancement. Several clinical studies have investigated the efficacy of TXI for detecting and visualizing gastrointestinal diseases, including oesophageal squamous cell carcinoma (ESCC), Barret's epithelium, gastric cancer, gastric mucosal atrophy and intestinal metaplasia. Although TXI is often more useful for detecting and visualizing gastrointestinal diseases than WLI, it remains unclear whether TXI outperforms other IEEs, such as narrow-band imaging (NBI), in similar functions, and whether the performance of TXI modes 1 and 2 are comparable. Therefore, large-scale prospective studies are needed to compare the efficacy of TXI to WLI and other IEEs for endoscopic evaluation of patients undergoing screening endoscopy. Here, we review the characteristics and efficacy of TXI for the detection and visualization of gastrointestinal diseases.Key MessagesTXI mode 1 can improve the visibility of gastrointestinal diseases and qualitative diagnosis, especially for diseases associated with colour changes.The enhancement of texture and brightness with TXI mode 2 enables the detection of diseases, and is ideal for use in the first screening of gastrointestinal tract.

Investigation of the New Advantages of Colonoscope Insertion with an Endoscopic Position Detection Unit.

BACKGROUND: The use of an endoscopic position detection unit (UPD) enables better and more objective understanding of the shape and position of the colonoscope. Here, we investigated the reproducibility of the insertion of a colonoscope with UPD. MATERIALS AND METHODS: Study participants were 122 patients who received a colonoscopy with UPD twice for the purpose of large bowel screening and surveillance. The mean age of participants was 69.7 ± 10.4 years, and the male-to-female ratio was 9.2:1. The colonoscope insertion technique was primarily based on the shaft-holding, shortening insertion method. The cecal intubation time was recorded; the method used for passing through the sigmoid/descending colon junction (SDJ) and the hepatic flexure. RESULTS: The mean cecal intubation time was 990 ± 511 s. The cecal intubation time and the patterns for passing through the SDJ and hepatic flexure were significantly correlated between the first and second colonoscopies. CONCLUSION: Use of a UPD revealed good reproducibility of colonoscope insertion. This is the first time we have proved that both time and pattern are inserted in much the same way for the first and second times. In patients' conducted UPD combination TCS after the second time, it was suggested that individual tailor-made insertions are possible based on the information from the first time.

Bleeding following Endoscopic Submucosal Dissection for Early Gastric Cancer in Surgically Altered Stomach.

INTRODUCTION: Few studies have focused on bleeding following endoscopic submucosal dissection (ESD) in surgically altered stomach. We aimed to reveal the bleeding risk in surgically altered stomach following ESD for early gastric cancer (EGC). METHODS: We enrolled patients with ESD for EGC at 33 institutions between 2013 and 2016. In study 1, we evaluated bleeding risk following ESD in surgically altered stomach, compared with whole stomach. In study 2, we evaluated factors associated with bleeding following ESD in patients with surgically altered stomach. RESULTS: Of 11,452 patients, 445 patients had surgically altered stomach with the bleeding rate following ESD of 4.9%. In study 1, the bleeding risk in surgically altered stomach was not significant (odds ratio [OR], 1.37; 95% confidence interval [CI], 0.87-2.17) in the multivariate logistic regression analysis. No significant results were obtained when the surgically altered stomach was subdivided into various types. In study 2, the multivariate logistic regression analysis revealed that independent risk factors for bleeding following ESD were ischemic heart disease (OR, 7.52; 95% CI, 2.00-28.25) and P2Y12 receptor antagonist (OR, 4.81; 95% CI, 1.21-19.14). DISCUSSION/CONCLUSION: In this nationwide study, we found that the bleeding risk of surgically altered stomach following ESD for EGC did not significantly differ from that of whole stomach. The risk factors for ESD in patients with surgically altered stomach were ischemic heart disease and P2Y12 receptor antagonist.