Impaired Glycosylation of Gastric Mucins Drives Gastric Tumorigenesis and Serves as a Novel Therapeutic Target.

BACKGROUND & AIMS: Gastric cancer is often accompanied by a loss of mucin 6 (MUC6), but its pathogenic role in gastric carcinogenesis remains unclear. METHODS: Muc6 knockout (Muc6-/-) mice and Muc6-dsRED mice were newly generated. Tff1Cre, Golph3-/-, R26-Golgi-mCherry, Hes1flox/flox, Cosmcflox/flox, and A4gnt-/- mice were also used. Histology, DNA and RNA, proteins, and sugar chains were analyzed by whole-exon DNA sequence, RNA sequence, immunohistochemistry, lectin-binding assays, and liquid chromatography-mass spectrometry analysis. Gastric organoids and cell lines were used for in vitro assays and xenograft experiments. RESULTS: Deletion of Muc6 in mice spontaneously causes pan-gastritis and invasive gastric cancers. Muc6-deficient tumor growth was dependent on mitogen-activated protein kinase activation, mediated by Golgi stress-induced up-regulation of Golgi phosphoprotein 3. Glycomic profiling revealed aberrant expression of mannose-rich N-linked glycans in gastric tumors, detected with banana lectin in association with lack of MUC6 expression. We identified a precursor of clusterin as a binding partner of mannose glycans. Mitogen-activated protein kinase activation, Golgi stress responses, and aberrant mannose expression are found in separate Cosmc- and A4gnt-deficient mouse models that lack normal O-glycosylation. Banana lectin-drug conjugates proved an effective treatment for mannose-rich murine and human gastric cancer. CONCLUSIONS: We propose that Golgi stress responses and aberrant glycans are important drivers of and promising new therapeutic targets for gastric cancer.

Association Between Vonoprazan and the Risk of Gastric Cancer After Helicobacter pylori Eradication.

BACKGROUND & AIMS: Potassium-competitive acid blockers (PCABs) have been increasingly used to treat upper gastrointestinal disorders, replacing proton pump inhibitors (PPIs). Whereas PPIs are associated with an increased risk of gastric cancer (GC) after Helicobacter pylori (Hp) eradication, it is uncertain whether PCABs carry the same risk. METHODS: Using a population-based claims database in Japan, we identified patients who were prescribed a clarithromycin-based first regimen of Hp eradication between 2015 and 2018. Patients who failed this regimen and those diagnosed with GC before or within 1 year after Hp eradication were excluded. We compared GC incidence between PCAB users and histamine type-2 receptor antagonist (H2RA) users, matching them on the basis of propensity scores calculated with considerations for age, sex, smoking, alcohol consumption, comorbidities, and co-administered medications. PCABs included only vonoprazan in this study. RESULTS: Among 54,055 patients, 568 (1.05%) developed GC during the follow-up period (mean, 3.65 years). The cumulative incidence of GC was 1.64% at 3 years, 2.02% at 4 years, and 2.36% at 5 years in PCAB users and 0.71% at 3 years, 1.04% at 4 years, and 1.22% at 5 years in H2RA users. The use of PCABs was associated with a higher GC risk (matched hazard ratio, 1.92; 95% confidence interval, 1.13-3.25; P = .016). Longer PCAB use and high-dose PCAB use were significantly associated with higher incidence of GC. Sensitivity analyses showed the risk of GC incidence among PCAB users was comparable with that of PPI users. CONCLUSIONS: The use of PCABs was associated with an increased risk of GC among Hp-eradicated patients, with duration/dose response effects.

Comparison of clinical utility of deep learning-based systems for small-bowel capsule endoscopy reading.

BACKGROUND AND AIM: Convolutional neural network (CNN) systems that automatically detect abnormalities from small-bowel capsule endoscopy (SBCE) images are still experimental, and no studies have directly compared the clinical usefulness of different systems. We compared endoscopist readings using an existing and a novel CNN system in a real-world SBCE setting. METHODS: Thirty-six complete SBCE videos, including 43 abnormal lesions (18 mucosal breaks, 8 angioectasia, and 17 protruding lesions), were retrospectively prepared. Three reading processes were compared: (A) endoscopist readings without CNN screening, (B) endoscopist readings after an existing CNN screening, and (C) endoscopist readings after a novel CNN screening. RESULTS: The mean number of small-bowel images was 14 747 per patient. Among these images, existing and novel CNN systems automatically captured 24.3% and 9.4% of the images, respectively. In this process, both systems extracted all 43 abnormal lesions. Next, we focused on the clinical usefulness. The detection rates of abnormalities by trainee endoscopists were not significantly different across the three processes: A, 77%; B, 67%; and C, 79%. The mean reading time of the trainees was the shortest during process C (10.1 min per patient), followed by processes B (23.1 min per patient) and A (33.6 min per patient). The mean psychological stress score while reading videos (scale, 1-5) was the lowest in process C (1.8) but was not significantly different between processes B (2.8) and A (3.2). CONCLUSIONS: Our novel CNN system significantly reduced endoscopist reading time and psychological stress while maintaining the detectability of abnormalities. CNN performance directly affects clinical utility and should be carefully assessed.

Investigation of the relationship between colonoscopy insertion difficulty factors and endoscope shape using an endoscopic position detection unit.

In this study, we investigated the relationship between the cecal intubation time (CIT) and the form and method used for passing through the sigmoid/descending colon junction (SDJ) and the hepatic flexure using an endoscopic position detection unit (UPD), with reference to various factors [age, sex, body mass index (BMI), history of abdominal and pelvic surgery, and diverticulum]. A total of 152 patients underwent colonoscopy with UPD. The mean age was 66.9 ±â€…12.4 years, and the male to female ratio was 3.6:1. The average CIT time was 14.3 ±â€…8.2 min. Age, number of experienced endoscopies, history of abdominal and pelvic surgery, BMI, and diverticulum were associated with prolonged CIT; SDJ passage pattern was straight: 8.6 ±â€…5.0, alpha loop: 11.8 ±â€…5.6, puzzle ring-like loop: 20.2 ±â€…5.0, reverse alpha loop: 22.4 ±â€…9.7, and other loop: 24.7 ±â€…10.5. The hepatic flexure passing method was in the following order: right rotation maneuver: 12.6 ±â€…6.6, push maneuver: 15.1 ±â€…5.9, and right rotation with positional change maneuver: 20.5 ±â€…7.2. In conclusion, colonoscopy with UPD revealed an association between CIT and SDJ passage pattern and hepatic flexure passing method.

Risk and preventive factors of early-onset colorectal neoplasms: endoscopic and histological database analysis.

BACKGROUND AND AIM: The incidence of early-onset colorectal neoplasms has been increasing in both Western and Eastern countries. However, the risks and preventive factors for these neoplasms in Eastern countries remain unclear. METHODS: The data of 5580 patients who underwent colonoscopy between 2016 and 2021 were retrospectively evaluated. The primary outcome was advanced colorectal neoplasm (ACRN), defined as advanced adenomas (adenoma ≥10 mm, or with high-grade dysplasia or villous component) or adenocarcinoma. The clinical factors associated with ACRNs were determined for each age category (≤50 and >50 years), and the differences between the two categories were assessed. Odds ratios adjusted for age and sex were calculated. RESULTS: Among 1001 patients (age ≤50 years), ACRN was found in 94 (9.4%). In this younger category, male sex (adjusted odds ratio [aOR]:2.34, 95% confidence interval [CI]:1.51-3.63) and a family history of colorectal cancer (aOR:2.14, 95% CI:1.17-3.89) were significantly associated with higher odds of developing ACRNs. ACRNs were detected in 726 (15.9%) of 4579 patients (age >50 years). In the older age category, smoking (aOR:1.32, 95% CI:1.08-1.63) was significantly associated with a higher risk of ACRNs. Exercise of >3.5 metabolic equivalent of task (METs) (aOR,0.80; 95% CI:0.67-0.96) was significantly associated with a lower risk of ACRNs. CONCLUSION: The development of early-onset ACRNs was primarily associated with congenital factors, whereas that of late-onset ACRNs was associated with acquired ones. Colonoscopy is recommended for young male patients, particularly for those with a family history of colorectal cancer.

The Association between Diverticular Rebleeding and Early-Morning Blood Pressure and Surge: A Prospective Observational Trial.

INTRODUCTION: Colonic diverticular bleeding is the major cause of lower gastrointestinal bleeding. Hypertension is a major risk factor for diverticular rebleeding. Direct evidence of an association between actual 24-h blood pressure (BP) and rebleeding is lacking. Therefore, we analyzed the association between 24-h BP and diverticular rebleeding. METHODS: We performed a prospective observational cohort trial involving hospitalized patients with colonic diverticular bleeding. We performed 24-h BP measurements (ambulatory BP monitoring [ABPM]) in the patients. The primary outcome was diverticular rebleeding. We evaluated the 24-h BP difference and the morning and pre-awaking BP surge between rebleeding and non-rebleeding patients. Morning BP surge was defined as early-morning systolic BP minus the lowest night systolic BP >45 mm Hg (highest quartile of morning BP surge). The pre-awaking BP surge was defined as the difference between morning BP and pre-awaking BP. RESULTS: Of 47 patients, 17 were excluded, leaving 30 who underwent ABPM. Of the 30 patients, 4 (13.33%) had rebleeding. The mean 24-h systolic and diastolic BP were 125.05 and 76.19 mm Hg in rebleeding patients and 129.98 and 81.77 mm Hg in non-rebleeding patients, respectively. Systolic BP at 5:00 (difference -23.53 mm Hg, p = 0.031) and 11:30 (difference -31.48 mm Hg, p = 0.006) was significantly lower in rebleeding patients than in non-rebleeding patients. Diastolic BP at 2:30 (difference -17.75 mm Hg, p = 0.023) and 5:00 (difference -16.12 mm Hg, p = 0.043) was significantly lower in rebleeding patients than in non-rebleeding patients. A morning surge was observed in one rebleeding patient and no non-rebleeding patients. The pre-awaking surge was significantly higher in rebleeding patients (28.44 mm Hg) than in non-rebleeding patients (9.30 mm Hg) (p = 0.015). CONCLUSION: Lower BP in the early-morning and a higher pre-awaking surge were risk factors for diverticular rebleeding. A 24-h ABPM can identify these BP findings and reduce the risk of rebleeding by enabling interventions in patients with diverticular bleeding.

Machine learning-based personalized prediction of gastric cancer incidence using the endoscopic and histologic findings at the initial endoscopy.

BACKGROUND AND AIMS: Accurate risk stratification for gastric cancer is required for optimal endoscopic surveillance in patients with chronic gastritis. We aimed to develop a machine learning (ML) model that incorporates endoscopic and histologic findings for an individualized prediction of gastric cancer incidence. METHODS: We retrospectively evaluated 1099 patients with chronic gastritis who underwent EGD and biopsy sampling of the gastric mucosa. Patients were randomly divided into training and test sets (4:1). We constructed a conventional Cox proportional hazard model and 3 ML models. Baseline characteristics, endoscopic atrophy, and Operative Link on Gastritis-Intestinal Metaplasia Assessment (OLGIM)/Operative Link on Gastritis Assessment (OLGA) stage at initial EGD were comprehensively assessed. Model performance was evaluated using Harrel's c-index. RESULTS: During a mean follow-up of 5.63 years, 94 patients (8.55%) developed gastric cancer. The gradient-boosting decision tree (GBDT) model achieved the best performance (c-index from the test set, .84) and showed high discriminative ability in stratifying the test set into 3 risk categories (P < .001). Age, OLGIM/OLGA stage, endoscopic atrophy, and history of malignant tumors other than gastric cancer were important predictors of gastric cancer incidence in the GBDT model. Furthermore, the proposed GBDT model enabled the generation of a personalized cumulative incidence prediction curve for each patient. CONCLUSIONS: We developed a novel ML model that incorporates endoscopic and histologic findings at initial EGD for personalized risk prediction of gastric cancer. This model may lead to the development of effective and personalized follow-up strategies after initial EGD.

Vonoprazan versus proton pump inhibitors for postendoscopic submucosal dissection bleeding in the stomach: a multicenter population-based comparative study.

BACKGROUND AND AIMS: The effectiveness of vonoprazan relative to that of proton pump inhibitors (PPIs) after gastric endoscopic submucosal dissection (ESD) is unclear. Although previous studies used post-ESD ulcer healing as the outcome measure, post-ESD bleeding rate is the most objective and appropriate outcome measure because it has less ascertainment bias. We aimed to compare the post-ESD bleeding rates between vonoprazan and PPIs. METHODS: This nationwide population-based retrospective cohort study was conducted between 2014 and 2018 and involved 9 hospitals. After 2 days of intravenous PPI administration, either vonoprazan or PPI was administrated from postoperative day 2 to 30. RESULTS: Overall, data of 1715 patients (627 patient pairs) were analyzed through propensity score matching. The vonoprazan group had significantly lower post-ESD bleeding rates than the PPI group (overall, 11.9% vs 17.2%, P = .008; bleeding between days 2 and 30, 7.8% vs 11.8%, P = .015). The readmission rate because of post-ESD bleeding was lower in the vonoprazan group (2.4% vs 4.1%, P = .081). Blood transfusion (2.1% vs 3.0%, P = .15) and additional surgery because of delayed perforation (.5% vs 1.0%, P = .32) were not significantly different between the 2 groups. No deaths within 30 days occurred in both groups. On Cox regression analysis, vonoprazan use, lesion location (antrum), aspirin use, direct oral anticoagulant use, and Charlson Comorbidity Index (≥2) were associated with an increased risk of post-ESD bleeding within 30 days. CONCLUSIONS: Vonoprazan has a lower post-ESD bleeding rate than PPIs. Further prospective studies are required to confirm these results.

Artificial intelligence versus expert endoscopists for diagnosis of gastric cancer in patients who have undergone upper gastrointestinal endoscopy.

AIMS: To compare endoscopy gastric cancer images diagnosis rate between artificial intelligence (AI) and expert endoscopists. PATIENTS AND METHODS: We used the retrospective data of 500 patients, including 100 with gastric cancer, matched 1:1 to diagnosis by AI or expert endoscopists. We retrospectively evaluated the noninferiority (prespecified margin 5 %) of the per-patient rate of gastric cancer diagnosis by AI and compared the per-image rate of gastric cancer diagnosis. RESULTS: Gastric cancer was diagnosed in 49 of 49 patients (100 %) in the AI group and 48 of 51 patients (94.12 %) in the expert endoscopist group (difference 5.88, 95 % confidence interval: -0.58 to 12.3). The per-image rate of gastric cancer diagnosis was higher in the AI group (99.87 %, 747 /748 images) than in the expert endoscopist group (88.17 %, 693 /786 images) (difference 11.7 %). CONCLUSIONS: Noninferiority of the rate of gastric cancer diagnosis by AI was demonstrated but superiority was not demonstrated.

Efficacy of Early Video Capsule Endoscopy for Acute Overt Lower Gastrointestinal Bleeding with Colonic Diverticulosis: A Prospective Observational Study.

BACKGROUND/AIMS: Although most patients with presumptive colonic diverticular bleeding (CDB) do not undergo a small bowel investigation in clinical practice, no prospective study supports this management. We evaluated the utility of early small bowel capsule endoscopy (CE) after negative colonoscopy results. METHODS: This prospective study evaluated the diagnostic yield of early small bowel CE (≤3 days from visit) for consecutive patients with acute-onset hematochezia, when colonoscopy found colonic diverticulosis but did not identify the definite bleeding source (n = 51; presumptive CDB). As a matched control for comparing clinical outcomes, presumptive CDB patients without CE (n = 51) were retrospectively extracted. RESULTS: On CE for the prospective cohort, the rates of total positive findings, P2 findings (high bleeding potential according to the P classification), and blood pooling in the colon were 57%, 12% (ulceration, 8%; angioectasia, 4%), and 24%, respectively. The rates of rebleeding within 30 and 365 days were 16% and 29% in the prospective cohort with CE, respectively, and were not significantly different from those in the retrospective cohort without CE (10% and 25%, respectively). In addition, thromboembolism and mortality within 30 and 365 days were not significantly different between those with and without CE. CONCLUSION: Early CE detected a suspected small bowel bleeding source in 12% of acute-onset presumptive CDB patients but did not significantly improve major clinical outcomes. Therefore, routine CE is unnecessary for presumptive CDB patients after colonoscopy (UMIN000026676).

Chemoprevention of Oesophageal Squamous-Cell Carcinoma and Adenocarcinoma: A Multicentre Retrospective Cohort Study.

BACKGROUND: Oesophageal cancer comprises 2 different histological variants: oesophageal squamous-cell carcinoma (ESCC) and adenocarcinoma (EAC). While there are multiple therapeutic options for both types, patients with advanced or metastatic oesophageal cancer still suffer from poor prognosis. AIMS: The study aimed to examine the association between the risk of oesophageal cancer and medications and to estimate the chemopreventive effects of commonly used drugs. METHODS: A multicentre retrospective cohort study was conducted using data from 9 hospital databases of hospitalized patients between 2014 and 2019. The primary outcomes were ESCC and EAC. The association of oesophageal cancer with drug use and clinical factors was evaluated. Odds ratios (ORs) were adjusted for age, sex, Charlson comorbidity index scores, and smoking with/without gastro-oesophageal reflux disease. RESULTS: The use of proton pump inhibitors (PPIs) (adjusted OR [aOR] 0.48, p < 0.0001), aspirin (aOR 0.32, p < 0.0001), cyclooxygenase-2 inhibitor (COX2I) (aOR 0.70, p = 0.0005), steroid (aOR 0.19, p < 0.0001), statin (aOR 0.43, p < 0.0001), and metformin (aOR 0.42, p < 0.0001) was associated with a lower risk of ESCC than that in non-use. The use of aspirin (aOR 0.33, p = 0.0006) and steroids (aOR 0.54, p = 0.022) was associated with a lower risk of EAC than that in non-use. CONCLUSION: COX2Is, statins, metformin, and PPIs could help in prevention of ESCC, and aspirin and steroids may be chemopreventive for both types of oesophageal cancer.

Chemoprevention for Colorectal Cancers: Are Chemopreventive Effects Different Between Left and Right Sided Colorectal Cancers?

BACKGROUND AND AIMS: Recent studies have suggested that right- and left-sided colorectal cancers (CRCs) are molecularly distinct. In this study, we examined the association between the risk of right- and left-sided CRC and drug use to estimate their chemopreventive effects METHODS: This multicenter retrospective cohort study was conducted using the data of hospitalized patients between 2014 and 2019 from nine hospital databases. The primary outcomes were right- and left-sided CRC. We evaluated the association of CRCs with drug use and clinical factors. Odds ratios adjusted for age, sex, Charlson Comorbidity Index scores, and smoking status were calculated. We also compared the transcriptional profiling in precancerous lesions, including sessile serrated lesions (SSLs) RESULTS: A total of 307,938 patients, including 2745 with right-sided CRC and 4819 with left-sided CRC, were analyzed. The use of nonsteroidal anti-inflammatory drugs (NSAIDs), aspirin, cyclooxygenase-2 inhibitors, and steroids was associated with a lower risk of both right- and left-sided CRCs. In contrast, statins, other lipid-lowering agents, and metformin were associated with a lower risk of left-sided CRC. Transcriptomic analysis showed that SSL, which predominantly develops in the right colon, was associated with a lower expression of lipid metabolism-related genes. CONCLUSIONS: Targeting lipid metabolism may be useful for chemoprevention of left-sided CRCs, while development of right-sided CRCs may be independent of this pathway.

Present status and the future of ultrathin endoscopy.

Endoscopic population-based screening for gastric cancer began in April 2016, and the use of transnasal ultrathin esophagogastroduodenoscopy (UT-EGD) has rapidly become popular. With UT-EGD, discomfort associated with an examination is reduced, patient satisfaction is high, and adverse effects on cardiopulmonary function are fewer. Consequently, UT-EGD is a good option for gastric screening in an aging society. Because of the narrower diameter of the endoscope, however, image quality is inferior to that obtained using transoral conventional esophagogastroduodenoscopy (C-EGD). As a result, lesions observed by UT-EGD must be viewed at close proximity and chromoendoscopy should be used concurrently, which is burdensome for the endoscopist. Recent innovations by endoscope manufacturers have enabled dramatic improvements in transnasal UT-EGD and facilitated Hi-Vision imaging. Furthermore, image enhancement that allows for observation on a par with transoral C-EGD is now feasible. In the future, UT-EGD will be equipped with functions that permit magnified endoscopic image. It is anticipated that a multiroute transition between transnasal and transoral UT-EGD will become possible.

Linked color imaging effectively detects the endoscopic atrophic border in transnasal endoscopy.

In oral endoscopy, linked color imaging (LCI) detects atrophic border and gastric mucosal diseases better than white light imaging (WLI), but its usefulness in transnasal endoscopy has not been fully investigated. Here, we retrospectively compared WLI and LCI using the L*a*b* color space in images from 57 patients aged ≥20 years who had undergone transnasal endoscopy as part of a health check-up from May 2016 to January 2017. We measured color differences at the atrophic/non-atrophic and fundic/pyloric mucosal borders. Gastritis severity scored using the Kyoto classification of gastritis was similar between the two techniques. However, in patients with current and with past Helicobacter pylori infection, color difference at the atrophic border was greater with LCI (21.58 ±â€…6.97 and 27.34 ±â€…10.32, respectively) than with WLI [14.42 ±â€…5.95 (p = 0.004) and 17.9 ±â€…8.48 (p<0.001)]; in those never infected with Helicobacter pylori, color difference at the fundic/pyloric mucosal border was greater with LCI than with WLI (p<0.001). Because of its enhancement of atrophic border detection, we recommend linked color imaging as the method of choice for transnasal endoscopy in health check-ups, particularly for identifying people at high risk of gastric cancer.

Association between dyspeptic symptoms and endoscopic findings based on the Kyoto classification of gastritis in Japanese male.

The Kyoto gastritis classification is used to categorize the endoscopic characteristics of Helicobacter pylori infection-associated gastritis. We aimed to clarify the association among endoscopic findings and abdominal dyspeptic symptoms in Japanese male. We administered a questionnaire to 418 subjects who underwent endoscopy as part of a health check-up from August 2003 to April 2004 to investigate the association among endoscopic findings of the Kyoto classification and the presence of dyspeptic symptoms. Logistic regression analyses were performed to evaluate risk based on dyspeptic symptoms. Among 418 health check-up subjects, 21.3% (89/418) reported dyspeptic symptoms in the questionnaire. The incidence of fundic gland polyp among patients with dyspeptic symptoms was 12.4% (11/89), which was significantly higher than that among non-symptomatic subjects (4.3%, 14/329, p = 0.004). Logistic regression analyses showed that fundic gland polyp was a risk factor for dyspeptic symptoms [odds ratio (OR): 3.413, 95% confidence interval (CI): 1.430-8.142], while short-segment Barrett's esophagus and male sex were protective factors (OR: 0.569, 95% CI: 0.349-0.928 and OR: 0.333, 95% CI: 0.117-0.948, respectively). In conclusion, Endoscopic findings of fundic gland polyp may be associated with dyspeptic symptoms, which in turn may be a useful marker of gastric condition.

Efficacy and Safety of Early vs Elective Colonoscopy for Acute Lower Gastrointestinal Bleeding.

BACKGROUND & AIMS: We performed a large, multicenter, randomized controlled trial to determine the efficacy and safety of early colonoscopy on outcomes of patients with acute lower gastrointestinal bleeding (ALGIB). METHODS: We performed an open-label study at 15 hospitals in Japan of 170 patients with ALGIB randomly assigned (1:1) to groups that underwent early colonoscopy (within 24 hours of initial visit to the hospital) or elective colonoscopy (24-96 hours after hospital admission). The primary outcome was identification of stigmata of recent hemorrhage (SRH). Secondary outcomes were rebleeding within 30 days, endoscopic treatment success, need for transfusion, length of stay, thrombotic events within 30 days, death within 30 days, and adverse events. RESULTS: SRH were identified in 17 of 79 patients (21.5%) in the early colonoscopy group vs 17 of 80 patients (21.3%) in the elective colonoscopy group (difference, 0.3; 95% confidence interval, -12.5 to 13.0; P = .967). Rebleeding within 30 days of hospital admission occurred in 15.3% of patients in the early colonoscopy group and 6.7% of patients in the elective colonoscopy group (difference, 8.6; 95% confidence interval, -1.4 to 18.7); there were no significant differences between groups in successful endoscopic treatment rate, transfusion rate, length of stay, thrombotic events, or death within 30 days. The adverse event of hemorrhagic shock occurred during bowel preparation in no patient in the early group vs 2 patients (2.5%) in the elective colonoscopy group. CONCLUSIONS: In a randomized controlled study, we found that colonoscopy within 24 hours after hospital admission did not increase SRH or reduce rebleeding compared with colonoscopy at 24-96 hours in patients with ALGIB. ClinicalTrials.gov, Numbers: UMIN000021129 and NCT03098173.

Automatic detection of various abnormalities in capsule endoscopy videos by a deep learning-based system: a multicenter study.

BACKGROUND AND AIMS: A deep convolutional neural network (CNN) system could be a high-level screening tool for capsule endoscopy (CE) reading but has not been established for targeting various abnormalities. We aimed to develop a CNN-based system and compare it with the existing QuickView mode in terms of their ability to detect various abnormalities. METHODS: We trained a CNN system using 66,028 CE images (44,684 images of abnormalities and 21,344 normal images). The detection rate of the CNN for various abnormalities was assessed per patient, using an independent test set of 379 consecutive small-bowel CE videos from 3 institutions. Mucosal breaks, angioectasia, protruding lesions, and blood content were present in 94, 29, 81, and 23 patients, respectively. The detection capability of the CNN was compared with that of QuickView mode. RESULTS: The CNN picked up 1,135,104 images (22.5%) from the 5,050,226 test images, and thus, the sampling rate of QuickView mode was set to 23% in this study. In total, the detection rate of the CNN for abnormalities per patient was significantly higher than that of QuickView mode (99% vs 89%, P < .001). The detection rates of the CNN for mucosal breaks, angioectasia, protruding lesions, and blood content were 100% (94 of 94), 97% (28 of 29), 99% (80 of 81), and 100% (23 of 23), respectively, and those of QuickView mode were 91%, 97%, 80%, and 96%, respectively. CONCLUSIONS: We developed and tested a CNN-based detection system for various abnormalities using multicenter CE videos. This system could serve as an alternative high-level screening tool to QuickView mode.

Automatic detection of colorectal neoplasia in wireless colon capsule endoscopic images using a deep convolutional neural network.

BACKGROUND: Although colorectal neoplasms are the most common abnormalities found in colon capsule endoscopy (CCE), no computer-aided detection method is yet available. We developed an artificial intelligence (AI) system that uses deep learning to automatically detect such lesions in CCE images. METHODS: We trained a deep convolutional neural network system based on a Single Shot MultiBox Detector using 15 933 CCE images of colorectal neoplasms, such as polyps and cancers. We assessed performance by calculating areas under the receiver operating characteristic curves, along with sensitivities, specificities, and accuracies, using an independent test set of 4784 images, including 1850 images of colorectal neoplasms and 2934 normal colon images. RESULTS: The area under the curve for detection of colorectal neoplasia by the AI model was 0.902. The sensitivity, specificity, and accuracy were 79.0 %, 87.0 %, and 83.9 %, respectively, at a probability cutoff of 0.348. CONCLUSIONS: We developed and validated a new AI-based system that automatically detects colorectal neoplasms in CCE images.

Comparison of inflammatory bowel disease relapse after top-down or step-up therapy: a population-based cohort study.

PURPOSE: The therapeutic effect of top-down therapy for inflammatory bowel disease (IBD) has not been fully evaluated in real-world clinical settings. We compared the effectiveness of top-down and step-up therapies for IBD. METHODS: We retrospectively evaluated patients who were admitted with IBD (Crohn's disease [CD] or ulcerative colitis [UC]) between 2012 and 2019 using the nationwide Japan Diagnosis Procedure Combination database. Patients who received immunomodulators or biologic agents at the start of observation were assigned to the top-down group and those who did not were enrolled in the step-up group. Relapse was the primary outcome, a composite outcome defined as surgery, new steroid or immunomodulator use, hospitalization, a new biologic agent, or switching biologic agents. RESULTS: We analyzed 6715 patients (CD, N = 3643; UC, N = 3072). Relapse occurred in 1982 CD cases (54.4%). The cumulative CD relapse incidence was 32.9% at 1 year and 61.3% at 5 years in the top-down group and 30.7% at 1 year and 58.6% at 5 years in the step-up group. Relapse occurred in 2032 UC cases (47.8%). The cumulative relapse incidence was 33.5% at 1 year and 50.0% at 5 years in the top-down group and 35.2% at 1 year and 51.6% at 5 years in the step-up group. No clinical factors associated with relapse were identified in patients with CD or UC. CONCLUSION: Compared with step-up therapy, top-down therapy was not associated with a decreased relapse risk in a real-world population of patients with CD or UC.

Natural history of upper and lower gastrointestinal bleeding in hemodialysis patients: A dual-center long-term cohort study.

BACKGROUND AND AIM: Knowledge on the risk of gastrointestinal (GI) bleeding in hemodialysis patients is limited. We evaluated the risk of GI bleeding in hemodialysis patients compared with non-hemodialysis patients. METHODS: We performed a retrospective cohort study from 1996 to 2017 at the Graduate School of Medicine, University of Tokyo, and Horinouchi Hospital. We analyzed patients on hemodialysis for chronic renal failure and controls not on hemodialysis. The primary endpoint was GI bleeding. A survival analysis was performed to estimate the cumulative incidence and hazard ratio of GI bleeding. RESULTS: A total of 14 451 patients were analyzed (417 hemodialysis and 14 034 non-hemodialysis patients). In total, 524 GI bleeding events occurred. Upper and lower GI bleeding occurred in 432 and 92 patients in the hemodialysis and non-hemodialysis groups, respectively. The most frequent source of upper and lower GI bleeding was gastric ulcer and colonic diverticular bleeding, respectively. The cumulative incidence of GI bleeding was 4.44% at 1 year, 7.15% at 3 years, and 10.40% at 5 years in hemodialysis patients; the respective rates were 2.35%, 2.98%, and 3.79% in non-hemodialysis patients during a mean follow-up period of 3.5 years. Hemodialysis was significantly associated with an increased risk of GI bleeding after adjustment (hazard ratio 1.67, P = 0.01, 95% confidence interval 1.13-2.50). CONCLUSIONS: Hemodialysis patients had a GI bleeding rate of 10% over 5 years, and hemodialysis was a risk factor for GI bleeding.