Intragastric bacterial infection and endoscopic findings in Helicobacter pylori-negative patients.

In the present study, the authors examined the association between gastric bacterial infection and gastric endoscopic findings in Helicobacter pylori (H. pylori)-negative patients. The subjects were 105 H. pylori-negative patients. The mean age was 72.8 ±â€…9.1 years. Endoscopy and gastric juice culture were performed. The presence or absence of endoscopic findings was checked according to the Kyoto classification of gastritis. Culture was positive in 69 patients (65.7%), with Streptococcus α-hemolytic being the most common (51 patients), followed by Neisseria sp. (43 patients). According to the univariate analysis, there was a significant difference between the results of culture and background factors in the use of gastric antisecretory drugs and between the results of culture and various endoscopic findings in atrophic gastritis, intestinal metaplasia, regular arrangement of collecting venule, mucosal swelling, sticky mucus, hyperplastic polyps, hematin, and gastric cobblestone-like lesions. Furthermore, multivariate analysis revealed significant differences in background factors such as the use of gastric antisecretory drugs and endoscopic findings only in patients with mucosal swelling. Endoscopic findings of non-H. pylori bacteria-positive gastritis differed from endoscopic findings of H. pylori-infected gastritis in several respects. In conclusion, our results suggest that non-H. pylori bacteria may infect the stomach and cause gastric inflammation, especially in patients who long term use gastric antisecretory drugs.

Long-term endoscopic gastric mucosal changes up to 20 years after Helicobacter pylori eradication therapy.

Helicobacter pylori eradication therapy reduces the risk of gastric cancer. However, it is unclear whether the severity of risk factors for gastric cancer such as atrophy and intestinal metaplasia are reduced after eradication in the long term. We aimed to study long-term changes in endoscopic risk factors for gastric cancer up to 20 years post-eradication. The endoscopic severity of gastritis according to the Kyoto Classification of Gastritis in 167 patients was retrospectively evaluated over an average follow-up 15.7 years. A significant improvement in mean total gastric cancer risk score (4.36 ± 1.66 to 2.69 ± 1.07, p < 0.001), atrophy (1.73 ± 0.44 to 1.61 ± 0.49, p = 0.004), and diffuse redness (1.22 ± 0.79 to 0.02 ± 0.13, p < 0.001) was observed compared to baseline in the Eradication group. However, there was no change in the never infection and current infection groups. The frequency of map-like redness increased over time until 15 years (3.6% to 18.7%, p = 0.03). The Cancer group had significantly higher risk scores at all time points. Endoscopic atrophy significantly improved in eradicated patients over long-term, suggested that eradication is one of the key elements in gastric cancer prevention. Individualized surveillance strategies based on endoscopic gastritis severity before eradication may be important for those at risk of gastric cancer.

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.

Metabolic Factors Associated with Endoscopic Atrophy, Intestinal Metaplasia, and Gastric Neoplasms in Helicobacter pylori-Positive Patients.

BACKGROUND: Previous studies demonstrate an association between metabolic factors and Helicobacter pylori-related gastric cancer. However, the association of gastric atrophy or intestinal metaplasia (IM) with these factors remains unknown. METHODS: Data on 1603 Helicobacter pylori-positive patients who underwent esophagogastroduodenoscopy between 2001 and 2021 were evaluated. The outcome measures were endoscopic atrophy, IM grade, and the incidence of endoscopically diagnosed and pathologically confirmed gastric neoplasms. Clinical factors associated with these findings were also determined. RESULTS: Advanced age; successful Helicobacter pylori eradication; and comorbidities including diabetes mellitus (DM), hypertension, dyslipidemia, and fib4 index were significantly associated with endoscopic gastric atrophy grade. Male sex; advanced age; and comorbidities including DM, hypertension, dyslipidemia, hyperuricemia, fatty liver, aortic calcification, and fib4 index were also significantly associated with endoscopic IM grade, whereas advanced age, successful Helicobacter pylori eradication, DM, fatty liver, and fib4 index were significantly associated with the incidence of gastric neoplasms. CONCLUSION: Several metabolic disorders, including DM, hypertension, dyslipidemia, hyperuricemia, and fatty liver disease, are risk factors for advanced-grade gastric atrophy, intestinal metaplasia, and gastric neoplasms. Risk stratification according to these factors, particularly those with metabolic disorders, would affect EGD surveillance for Helicobacter pylori-positive patients.

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.

Special Issue: The Role of Gut Microbiota in Gastrointestinal Cancers-From Pathogenesis to Therapeutic Perspectives.

Associations between the gut microbiota and gastrointestinal carcinogenesis have been intensively studied [...].

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.

Association of probiotic use with nivolumab effectiveness against various cancers: A multicenter retrospective cohort study.

BACKGROUND: Previous studies have revealed an association between probiotic use and effectiveness of immune checkpoint inhibitors in renal and lung cancers. However, little is known regarding other cancers, including gastrointestinal cancer. METHODS: To address this issue, we conducted a multicenter retrospective cohort study and the duration of nivolumab treatment for various cancers was compared between probiotic users and non-users. RESULTS AND CONCLUSIONS: In total, 488 patients who received nivolumab therapy were included. In all cancers, no significant differences in treatment duration of nivolumab were observed between probiotic users and non-users (median 62.0 vs. 56.0, hazard ratio = 1.02, p = 0.825), whereas probiotic use, compared with non-use, in patients with gastric cancer was significantly associated with a longer duration of nivolumab treatment (55.0 vs. 31.0 days, hazard ratio = 0.69, p = 0.039). In conclusion, probiotics may improve the response to nivolumab and potentially prolong progression-free survival in patients with gastric cancer.

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.

Improved Object Detection Artificial Intelligence Using the Revised RetinaNet Model for the Automatic Detection of Ulcerations, Vascular Lesions, and Tumors in Wireless Capsule Endoscopy.

The use of computer-aided detection models to diagnose lesions in images from wireless capsule endoscopy (WCE) is a topical endoscopic diagnostic solution. We revised our artificial intelligence (AI) model, RetinaNet, to better diagnose multiple types of lesions, including erosions and ulcers, vascular lesions, and tumors. RetinaNet was trained using the data of 1234 patients, consisting of images of 6476 erosions and ulcers, 1916 vascular lesions, 7127 tumors, and 14,014,149 normal tissues. The mean area under the receiver operating characteristic curve (AUC), sensitivity, and specificity for each lesion were evaluated using five-fold stratified cross-validation. Each cross-validation set consisted of between 6,647,148 and 7,267,813 images from 217 patients. The mean AUC values were 0.997 for erosions and ulcers, 0.998 for vascular lesions, and 0.998 for tumors. The mean sensitivities were 0.919, 0.878, and 0.876, respectively. The mean specificities were 0.936, 0.969, and 0.937, and the mean accuracies were 0.930, 0.962, and 0.924, respectively. We developed a new version of an AI-based diagnostic model for the multiclass identification of small bowel lesions in WCE images to help endoscopists appropriately diagnose small intestine diseases in daily clinical practice.

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.

Non-Helicobacter pylori Gastric Microbiome Modulates Prooncogenic Responses and Is Associated With Gastric Cancer Risk.

Background and Aims: Although Helicobacter pylori is the most important bacterial carcinogen in gastric cancer (GC), GC can emerge even after H. pylori eradication. Studies suggest that various constituents of the gastric microbiome may influence GC development, but the role of individual pathogens is unclear. Methods: Human gastric mucosal samples were analyzed by 16SrRNA sequencing to investigate microbiome composition and its association with clinical parameters, including GC risk. Identified bacteria in the stomach were cocultured with gastric epithelial cells or inoculated into mice, and transcriptomic changes, DNA damage, and inflammation were analyzed. Bacterial reads in GC tissues were examined together with transcriptomic and genetic sequencing data in the cancer genome atlas dataset. Results: Patients after Helicobacter pylori eradication formed 3 subgroups based on the microbial composition revealed by 16SrRNA sequencing. One dysbiotic group enriched with Fusobacterium and Neisseria species was associated with a significantly higher GC incidence. These species activated prooncogenic pathways in gastric epithelial cells and promoted inflammation in mouse stomachs. Sugar chains that constitute gastric mucin attenuate host-bacteria interactions. Metabolites from Fusobacterium species were genotoxic, and the presence of the bacteria was associated with an inflammatory signature and a higher tumor mutation burden. Conclusion: Gastric microbiota in the dysbiotic stomach is associated with GC development after H. pylori eradication and plays a pathogenic role through direct host-bacteria interaction.

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.