Helicobacter pylori (H. pylori) associated gastritis, marked by chronic gastric inflammation, heightens gastric cancer risk by fostering a malignancy-prone microenvironment. Disruption of the biorhythm contribute to the onset of various gastrointestinal disorders, such as gastric dyspepsia, gastric ulcers, and cancer. We aimed to investigate the functional roles and regulatory mechanisms of key biorhythm molecules in H. pylori associated gastritis. We investigated biorhythm gene expression in H. pylori-infected human gastric tissues and found significant impact on NFIL3 expression. Animal studies confirmed that H. pylori controls NFIL3 biorhythm. Clinical samples indicated a correlation between NFIL3 and gastritis severity, suggesting a regulatory role. Then, we found that H. pylori disrupt NFIL3 expression rhythm in gastric epithelial cells (GECs) through the CagA-activated ERK-SP1 pathway. Additionally, cytokines IL1β and TNFα enhance this disruption. RNA-seq and Gene set enrichment analysis (GSEA) indicated that NFIL3 positively regulates the inflammatory response during H. pylori infection. Our research highlights the crucial role of the biorhythm molecule NFIL3 in H. pylori associated gastritis. Modulating biorhythm molecules could be a promising therapeutic approach to manage disease progression, given their impact on gastrointestinal pathology.

In a transcriptome-wide association study, we deciphered susceptibility genes that may predict gastric cancer (GC) risk and modify the effects of Helicobacter pylori (H. pylori) treatment.

Genetically predicted expression models of 4518 genes were developed based on the GTEx and applied to a nested case-control study (935 GCs and 1869 controls) of the Mass Intervention Trial in Linqu, Shandong Province (MITS), with genes associated with GC risk further validated in BioBank Japan (7921 GCs and 159,201 controls). Transcriptome risk scores (TRSs) integrating key genes were constructed, utilizing imputed transcriptomes from the Shandong Intervention Trial (SIT) and UK Biobank, and observed transcriptomes from the National Upper Gastrointestinal Cancer Early Detection (UGCED) program. We also examined whether TRS may modify the association of H. pylori infection and anti-H. pylori treatment with GC risk.

Integrating 11 independent GC-associated genes identified based on the MITS (FDR-q < 0.05) and BioBank Japan (P < 0.05), the TRS demonstrated a dose-dependent association with an elevated risk of incident GC in both the SIT (P-trend = 0.003) and UK Biobank (P-trend = 0.008), and exhibited an upward trend as gastric lesions progressed based on the UGCED program (P-trend = 5.01 × 10-4). In the SIT, the increased risk of GC associated with H. pylori infection (P-interaction = 0.03) and beneficial effect of successful H. pylori eradication (P-interaction = 0.05) were significant for individuals with high TRSs.

We identified a gene panel which may predict GC risk across populations of multiple ancestries, which offers important insights into GC risk stratification and presents a precision approach to primary prevention.

Funders are listed in the Acknowledgement.

Metabolic profiling of the crude ethanolic extract of Gliricidia sepium (Jacq.) Kunth. ex. Walp. stem ethanolic extract (GSS) was conducted using ultra-high performance quadrupole time of flight mass spectrometry/mass spectrometry (UHPLC-QTOF-MS/MS) in negative mode, resulting in the identification of 23 compounds belonging to various classes such as flavonoids, fatty acids, triterpenoid saponins, and phenolic acids. Notably, eight flavonoids including kaempferol-3-O-robinoside-7-O-rhamnoside, isoquercitrin, kaempferol-3-O-rutinoside, apigenin-7-glucoside, kaempeferol-7-O-rhamnoside, luteolin, apigenin, and liquiritigenin, along with two phenolic acids (4-hydroxycinnamic acid and 2-hydroxyhydrocinnamic acid) and four triterpenoid saponins (soyasaponin I, soyasaponin II, soyasaponin III, and kaikasaponin III) were dereplicated. Additionally, nine fatty acid derivatives were identified, including azelaic acid and 2-isopropyl malic acid. Molecular networking analysis revealed the formation of clusters among compounds while others do not form clusters. Further analysis indicated that the GSS ethanolic extract exhibited a total phenolic content of 38.78 ± 1.609 µg of gallic acid equivalent/mg and a total flavonoid content of 5.62 ± 0.50 µg of rutin equivalent/mg. Biological evaluations showed that GSS ethanolic extract mitigated gastric tissue injury induced by pyloric ligation, with a notable reduction in oxidative stress marker reactive oxygen species levels and inflammatory cytokines interleukin-6 and tumor necrosis factor-alpha levels. Additionally, it enhanced superoxide dismutase and inhibitor of nuclear factor kappa B alpha levels, while lowering the expression of inducible nitric oxide synthase. Histopathological examination revealed significant improvements in gastric tissue morphology in GSS-treated groups compared to the control group. Molecular docking studies indicated potential interactions between GSS ethanolic extract compounds and various target proteins involved in oxidative stress, inflammation, and gastric protection in gastritis. This study aims to investigate the potential gastroprotective activity of GSS ethanolic extract against gastritis induced via pyloric ligation.

Autoimmune gastritis (AIG) is an important health problem and a risk factor for gastric neoplasms. This study assessed the diagnostic performance of different assays for anti-parietal cell antibodies (APCA) and anti-intrinsic factor antibodies (AIFA) in patients with histologically confirmed AIG.

This prospective, multicenter study included 50 AIG patients and 93 controls. The diagnostic performance of fluorescent enzyme immunoassay (FEIA) and immunoblot was evaluated for the detection of both APCA and AIFA, while indirect immunofluorescence (IIF) was assessed for APCA only.

Overall, AIFA detection using FEIA demonstrated slightly better performance (specificity [Sp] 100 %, positive predictive value [PPV] 100 %, negative predictive value [NPV] 75 %) compared to immunoblot (Sp 98.9 %, PPV 94.1 %, NPV 73 %). However, both methods showed low sensitivity (Se): 38 % for FEIA and 32 % for immunoblot. When the FEIA cut-off was adjusted using ROC curve analysis, Se increased to 50 %, while maintaining high Sp (98.9 %). For APCA detection, Se was similar across all methods (∼80 %), but Sp varied: immunoblot showed lower Sp (89.3 %) compared to IIF (98.8 %) and FEIA (95.7 %). PPV was highest for IIF (97.5 %), followed by FEIA (89.9 %) and immunoblot (89.3 %). NPV was lowest for immunoblot (80 %), while IIF and FEIA showed comparable values (89.5 % and 90.9 %, respectively). Adjusting the FEIA cut-off for APCA increased Sp to 98.9 % without reducing Se (76 %). Combining AIFA and APCA testing improved diagnostic performance, yielding a sensitivity of 90 % and specificity of 95.7 %.

FEIA offers superior diagnostic accuracy for APCA and AIFA testing in AIG. The highest diagnostic yield for AIG is observed when both APCA and AIFA are assessed. This approach could be clinically applicable in the screening for AIG and diagnostic process of AIG.

Introduction. Autoimmune metaplastic atrophic gastritis (AMAG, also termed autoimmune gastritis) is a chronic gastritis of autoimmune pathogenesis. Although its clinical and pathological features are well-documented in many countries, data from Middle Eastern populations remain scarce. This study examined the prevalence of AMAG in gastric specimens from the region, specifically from Saudi Arabia. Methods. We conducted a retrospective review of the pathology database of gastric specimens with a diagnosis of AMAG between 2020 and 2023. Detailed clinical, endoscopic, and pathological features of identified features were described. Result. Of the 978 gastric biopsies received, 17 patients were diagnosed with AMAG. The cohort comprised 11 women (64.7%) and 6 men (35.3%), presenting at a median age of 50 years (range: 32-85). Clinical manifestations varied widely, from abdominal pain (n = 6), dyspepsia (n = 2), symptomatic anemia with significant vitamin B12 deficiency (2 of 17) to asymptomatic/incidentally diagnosed patients (5 of 17). The tissue samples showed varying histological characteristics, with some showing lymphoplasmacytic infiltrate, mucosal atrophy, and hyperplasia of enterochromaffin-like cells. Conclusion. The observed prevalence of AMAG in our study aligns with global averages reported for other populations. The diverse clinical presentations highlight the need for awareness of findings in AMAG in gastric biopsies to ensure appropriate clinical management.

The eradication of Helicobacter pylori (H. pylori) at a younger age is considered effective in preventing gastric cancer. Toward this goal, we introduced primary H. pylori screening into routine high school health screenings in 2007. The present study aimed to elucidate the clinicopathological characteristics of H. pylori-infected students and evaluate the effectiveness of H. pylori screening in high school populations.

Primary screening using a urinary anti-H. pylori antibody test was conducted on high school students from 2007 to 2017. Students who tested positive for this examination were recommended secondary screening by esophagogastroduodenoscopy (EGD), with eradication therapy for those with confirmed H. pylori infection. We analyzed data from 2007 to 2011 as the early period and from 2012 to 2017 as the late period.

Over 11 years, 5178 of 5193 (99.7%) subjects received primary screening, among which 184 students (3.6%) tested positive. The primary screening-positive rate decreased significantly from 4.7% in the early period to 2.8% in the late period (p < 0.01). EGD as secondary screening in 103 students (56%) revealed nodular gastritis (83.3%) as the most common endoscopic finding. H. pylori infection was diagnosed in 90 students (87.4%). The resistance rate of H. pylori to clarithromycin was 41.1%. The initial eradication therapy success rate by treatment selection according to H. pylori susceptibility was 96.5%.

The introduction of H. pylori screening into school health checkups achieved high participation rates and appeared useful for identifying and treating H. pylori infection in young populations.

Although the urea breath test (UBT) is widely used as a representative monitoring test after Helicobacter pylori eradication, false-negative results can occur because of the gray zone related to its cutoff value. This study aimed to compare the diagnostic performances of the rapid urease test (RUT), the RUT with sweeping method, and the UBT, and to investigate the role of the sweeping method in the gray zone of UBT values.

We retrospectively reviewed 216 patients who received standard first-line H. pylori eradication treatments (n=216). All participants underwent to testing using the sweeping method and UBT on the same day. The sensitivity, specificity, and accuracy were analyzed to compare the two methods.

The sensitivity (0.537 vs 0.806, p=0.002) and accuracy (0.843 vs 0.870, p=0.026) of the UBT were inferior to those of the sweeping method. A total of 31 individuals tested positive for H. pylori according to the UBT, whereas 54 individuals tested positive according to the sweeping method. In the group for which the gold standard definition indicated H. pylori positivity but UBT results were negative (n=31), all individuals had a UBT value under 2.5‰. In the multivariate logistic regression model, a UBT value of 1.4‰ to 2.5‰ increased the risk of false-negative results by 6.5 times (odds ratio, 6.5; 95% confidence interval, 2.077 to 20.288; p=0.001).

After H. pylori eradication, false-negative results can occur for individuals undergoing the UBT, primarily for values below the UBT cutoff. The RUT with the sweeping method can potentially help detect H. pylori in the gray zone of the UBT, improving diagnostic accuracy.

The histopathological effects of duodenogastric reflux (DGR) in children remain poorly described. This study aimed to evaluate and compare the gastric histopathological findings of pediatric patients with endoscopically confirmed DGR gastritis and those without, to identify potential morphological changes associated with bile reflux in childhood. This retrospective study compared children with endoscopically confirmed DGR to age- and sex-matched controls without DGR. Gastric biopsy samples were re-evaluated by a single pathologist blinded to clinical data. Histopathological features, including inflammation severity, activity, fibrosis, vascular congestion, edema, foveolar hyperplasia, the presence of Helicobacter pylori, lymphoid aggregates, reactive gastropathy, intestinal metaplasia, and glandular atrophy were compared. Logistic regression was used to identify significant predictors of DGR. A total of 73 patients with DGR and 65 controls were included. Fibrosis (60.2% vs. 9.2%, p < 0.001), congestion (63.0% vs. 27.7%, p < 0.001), foveolar hyperplasia (32.9% vs. 6.2%, p < 0.001), and edema (24.7% vs. 6.2%, p = 0.003) were significantly more common in the DGR group. Logistic regression identified foveolar hyperplasia (OR 10.67), edema (OR 9.01), fibrosis (OR 6.98), and congestion (OR 5.85) as independent predictors of DGR.

Fibrosis, congestion, foveolar hyperplasia, and edema are significantly associated with DGR in pediatric patients and may serve as supportive histological markers for diagnosis.

• DGR in children lacks a standardized diagnostic method, with endoscopy and histopathology being commonly used. • Histopathological features such as foveolar hyperplasia and fibrosis are known in adults but less studied in children.

• This study identifies fibrosis, congestion, foveolar hyperplasia, and edema as significant histopathological markers in pediatric DGR. • It suggests that endoscopic findings, combined with histopathology, can aid in the diagnosis of DGR in children.

We aimed to evaluate the consistency between endoscopic grading of gastric intestinal metaplasia (EGGIM) and the operative link on gastric intestinal metaplasia assessment (OLGIM) staging, as well as the value of endoscopic grading of gastric intestinal metaplasia (GIM) in early gastric cancer (EGC) risk.

The sample size was estimated to be at least 210 patients. To evaluate GIM, EGGIM staging was used during magnifying endoscopy with narrow-band imaging, while the OLGIM staging was carried out according to the updated Sydney system. The consistency between the two scoring systems and the accuracy of EGGIM in diagnosing OLGIM III/IV cases were evaluated. EGC risk was evaluated using the Kimura-Takemoto classification, the operative link on gastritis assessment (OLGA)/OLGIM, and EGGIM.

Among the 210 patients, 68 (32.4%) had (previous) EGC and 142 (67.6%) had chronic atrophic gastritis (CAG). EGGIM and OLGIM staging showed good consistency (κ = 0.805, U = 12.620, p < 0.001) in diagnosing OLGIM III/IV GIM, with an area under the receiver operating characteristic curve for EGGIM of 0.95. Using a cut-off value of > 4, the sensitivity and specificity were 95.7% and 91.4%, respectively. The EGGIM score was higher in the EGC group than in the CAG group (4.93 vs. 3.92, p < 0.001).

EGGIM shows good diagnostic performance and consistency with OLGIM, which can simplify endoscopic surveillance by reducing the need for biopsy. The EGGIM score is associated with EGC risk, and endoscopic surveillance is recommended for patients with EGGIM score > 4.

With the assistance of ENDOANGEL, a study was conducted at Hainan General Hospital to evaluate the effect of artificial intelligence (AI) system on the detection of gastrointestinal precancerous lesions.

The prospective, randomized, pretest and post-test, single-center clinical trial compared the detection rates of gastric precancerous lesions and intestinal adenomas between baseline and post-intervention phase among traditional digestive endoscopy (control groups i and ii, and experimental group i) and AI-assisted endoscopy (experimental group ii). Additionally, the effect of AI on the detection rate of different seniority physicians was analyzed.

AI assistance significantly increased the detection rates of intestinal metaplasia (experimental group ii vs control group ii: 14.23 % vs 9.15 %, P = 0.013), atrophy (experimental group ii vs control group ii: 22.76 % vs 17.28 %, P = 0.031) and intestinal adenomas (experimental group ii vs control group ii: 48.52 % vs 24.58 %, P < 0.001). The improvement was particularly notable among junior doctors, with significant enhancements in the detection rates of intestinal metaplasia (experimental group ii vs control group ii: 14.39 % vs 9.09 %, P = 0.008), atrophy (experimental group ii vs control group ii: 22.04 % vs 15.31 %, P = 0.004), and intestinal adenomas (experimental group ii vs control group ii: 45.18 % vs 29.27 %, P = 0.002).

AI systems have the potential to significantly improve the detection rates of precancerous conditions, particularly among less experienced endoscopists. This advancement can lead to more accurate and appropriate follow-up and review strategies for patients, ultimately reducing the risk of missed early cancer diagnoses.

To investigate the association between atrophy severity and antiparietal cell antibody (APCA) levels in South and Southeast Asia.

APCA is an autoantibody that damages gastric parietal cells; autoimmune gastritis (AIG) is a chronic gastric inflammatory disease related to APCA and severe predominant corpus atrophy. Although a positive APCA result is a key clinical diagnostic tool for AIG, its rates vary widely among ethnic groups, and its exact relationship with AIG and predominant corpus atrophy remains unclear.

Associations between histopathology-assessed and endoscopy-assessed atrophy, APCA positivity rates, Helicobacter pylori status, and pepsinogen levels were investigated in 1982 symptomatic patients from Vietnam, Thailand, Myanmar, Bangladesh, and Nepal.

Overall, 38.5% of participants were negative for Helicobacter pylori infection, while 57.6% had a current infection. A positive APCA result, defined as a titer >10, was present in 44.0% of participants (95% confidence interval: 41.8%-46.3%, 873/1982). Pathologic atrophy, corpus atrophy, and predominant corpus atrophy were found in 8.7% (169/1982), 5.1% (101/1982), and 4.1% (81/1982) of participants, respectively. Positive APCA rates significantly differed among countries (10.6% to 63.8%, P<0.001). No significant correlation was found between APCA results and the presence or severity of atrophy.

Although APCA positivity was high among symptomatic patients from South and Southeast Asian countries, few had severe predominant corpus atrophy or positive pepsinogen tests, which suggests a low rate of AIG in this population. Long-term surveillance of APCA-positive individuals is necessary to determine the clinical significance of a positive APCA result without AIG.

Autoimmune metaplastic atrophic gastritis (AMAG) is a chronic immune-mediated form of gastritis characterized by damage to oxyntic cells, ultimately resulting in both iron deficiency with or without anemia and pernicious anemia. The current dogma is that AMAG is a disease of White Northern European women of advanced age. We, therefore, sought to examine the prevalence of AMAG in biopsies obtained from populations enriched for self-identified Hispanics for cross-comparison against data from previously reported populations enriched for self-identified White, non-Hispanic patients. To that end, we prospectively collected 1708 sequential gastric biopsies performed at the University of Miami Hospitals/Jackson Health Systems clinics from 1692 patients over a 1-year period as well as pertinent clinical parameters. These Florida data were then compared against data previously collected from the Baltimore population, which has far lower numbers of Hispanic patients. Self-identified race and/or ethnicity were used. From these 1692 patients, we identified 79 patients (4.6%) with AMAG. These included 60 women (76%) and 19 men (24%), with a F:M ratio of 3.1:1. Patients had a median age of 60 years (range: 15-83). Self-identified race and/or ethnicity were: 60 (76.0%) Hispanic, 9 (11.4%) Black, 9 (11.4%) White, and 1 Asian (1.2%). The median age at initial presentation was: 51 years (range: 15-83) in Hispanics, 77.2 years (range: 46-74) in Blacks, 59 years (range: 49-79) in Whites, and 58 years in the only Asian patient. The overall demographics of AMAG largely mirrored the Florida population, with an over-representation of Hispanics (Florida inhabitants self-report as 70% Hispanic). The overall 4.6% prevalence of AMAG in the Florida population differed significantly from the 1.1% in Baltimore (p < .00001), a finding that presumably reflects the large Hispanic population. In fact, the prevalence of AMAG is far higher in Hispanic patients. Awareness of these data should increase recognition of AMAG in this population.

This multi-center, randomized, double-blind, placebo-controlled study aimed to evaluate the clinical efficacy and safety of Elian Granule in treating chronic atrophic gastritis (CAG).

Over a 24-week period, 240 CAG patients were randomized to receive either Elian Granule or placebo. Primary outcomes included histological improvement of gastric mucosa via biopsy, while secondary outcomes assessed dyspepsia symptom scores and quality of life (QOL) scores. Safety was monitored through physical examinations, laboratory tests (blood and urine tests, liver function, and renal function), and electrocardiograms (ECGs).

The Elian Granule group exhibited significantly higher improvement rates in gastric mucosal atrophy (76.29% vs. 48.96%, P < 0.001) and intestinal metaplasia (62.89% vs. 34.38%, P < 0.001) compared to the placebo group. Total dyspepsia scores improved at 4, 12, and 24 weeks (P < 0.001), the individual symptom scores showed significant improvement in epigastric pain, epigastric distension, epigastric discomfort, early satiety, heartburn, belching and acid reflux at both the 4-week and 12-week timepoints (P < 0.05, P < 0.01, P < 0.001), of these, epigastric pain, epigastric distension, early satiety, belching and acid reflux maintained their statistically significant improvement through the 24-week evaluation period (P < 0.05, P < 0.01, P < 0.001). The total effective rate for symptom relief was 85.57% in the Elian group versus 47.92% in the placebo group (P < 0.001). QOL scores for physical health (GH, PF, BP, and PCS total score) and mental health (VT, SF, MH, and MCS total score) also improved significantly (P < 0.05, P < 0.01). No adverse impact was observed.

Elian Granule significantly improves gastric mucosal atrophy and intestinalization, alleviates dyspeptic symptoms, and enhances QOL in CAG patients, demonstrating a favorable safety profile.

http://itmctr.ccebtcm.org.cn/zh-CN/Home/ProjectView?pid=7a00ecee-da6a-4939-bae1-e6a58cd97cdb, identifier ChiMCTR2000003929, 2020-9-13.

Detecting gastric precancerous lesions (GPLs) is critical for the early diagnosis and treatment of gastric cancer. Endoscopy combined with tissue examination is an important method for detecting GPLs. However, negative biopsy results often increase patients' risks, economic burdens, and lead to additional healthcare costs. Improving the detection rate of GPLs and reducing the rate of negative biopsies is currently a key focus in endoscopic quality control.

To explore the relationships between the endoscopist biopsy rate (EBR), qualifications of endoscopists and endoscopic assistants, and detection rate of GPLs.

EBR, endoscopists, and endoscopic assistants were divided into four groups: Low, moderate, high, and very high levels. Multivariable logistic regression analysis was used to analyze the relationships between EBR and the qualifications of endoscopists with respect to the detection rate of positive lesions. Pearson and Spearman correlation analyses were used to evaluate the correlation between EBR, endoscopist or endoscopic assistant qualifications, and the detection rate of positive lesions.

Compared with those in the low EBR group, the odds ratio (OR) values for detecting positive lesions in the moderate, high, and very high EBR groups were 1.12 [95% confidence interval (CI): 1.06-1.19, P < 0.001], 1.22 (95%CI: 1.14-1.31, P < 0.001), and 1.38 (95%CI: 1.29-1.47, P < 0.001), respectively. EBR was positively correlated with the detection rate of gastric precancerous conditions (atrophic gastritis/intestinal metaplasia) (ρ = 0.465, P = 0.004). In contrast, the qualifications of the endoscopists were positively correlated with GPLs detection (ρ = 0.448, P = 0.005). Compared to endoscopists with low qualification levels, those with moderate, high, and very high qualification levels endoscopists demonstrated increased detection rates of GPLs by 13% (OR = 1.13, 95%CI: 0.98-1.31), 20% (OR = 1.20, 95%CI: 1.03-1.39), and 32% (OR = 1.32, 95%CI: 1.15-1.52), respectively. Further analysis revealed that the qualifications of endoscopists were positively correlated with the detection rates of GPLs in the cardia (ρ = 0.350, P = 0.034), angularis (ρ = 0.396, P = 0.015) and gastric body (ρ = 0.453, P = 0.005) but not in the antrum (ρ = 0.292, P = 0.079). Moreover, the experience of endoscopic assistants was positively correlated with the detection rate of precancerous lesions by endoscopists with low or moderate qualifications (ρ = 0.427, P = 0.015).

Endoscopists and endoscopic assistants with high/very high qualifications, but not EBR, can improve the detection rate of GPLs. These results provide reliable evidence for the development of gastroscopic quality control indicators.

Fecal calprotectin (FC) is a marker commonly used in the diagnosis and follow-up of inflammatory bowel diseases (IBD). However, other gastrointestinal conditions, like H. pylori (HP) infection, can result in increased neutrophil activity as well. We set out to assess the impact of HP infection on FC and downstream gastrointestinal care via a retrospective study.

In this study, we collected data from two institutions in Brooklyn, NY, in a high immigrant density community. We reviewed data from patients who underwent esophagogastroduodenoscopy (EGD) between January 2017 and October 2022. Patients aged 6-18 years old with an FC level 6 months prior to EGD and HP testing were included.

Of 129 patients, 37 (28.7%) tested positive for HP infection. The mean FC level was significantly elevated in HP-positive patients (241.2, confidence interval [CI]: 161.0-321.3) as compared with HP-negative patients (88.1, CI: 59.1-117.0) (p < 0.001). Patients with higher FC levels were also more likely to undergo colonoscopies (p = 0.003).

HP infection is associated with increased calprotectin, and calprotectin increases in HP patients are associated with an increased risk of colonoscopy.

Gastric premalignant conditions (GPMC) are common and include atrophic gastritis, gastric intestinal metaplasia, dysplasia, and certain gastric epithelial polyps. GPMC have an increased risk of progression to gastric adenocarcinoma. Gastric cancer (GC) in the United States represents an important cancer disparity because incidence rates are 2- to 13-fold greater in non-White individuals, particularly early-generation immigrants from regions of high GC incidence. The US 5-year survival rate for GC is 36%, which falls short of global standards and is driven by the fact that only a small percentage of GC in the US is diagnosed in the early, curable stage. This document represents the first iteration of American College of Gastroenterology guidelines on this topic and encompasses endoscopic surveillance for high-risk patients with GPMC, the performance of high-quality endoscopy and image-enhanced endoscopy for diagnosis and surveillance, GPMC histology criteria and reporting, endoscopic treatment of dysplasia, the role of Helicobacter pylori eradication, general risk reduction measures, and the management of autoimmune gastritis and gastric epithelial polyps. There is insufficient evidence to make a recommendation on upper endoscopic screening for GC/GPMC detection in US populations deemed high-risk for GC. Surveillance endoscopy is recommended for individuals at high risk for GPMC progression, as defined by endoscopic, histologic, and demographic factors, typically every 3 years, but an individualized interval may be warranted. H. pylori testing, treatment, and eradication confirmation are recommended in all individuals with GPMC. Extensive high-quality data from US populations regarding GPMC management are lacking, but continue to accrue, and the quality of evidence for the recommendations presented herein should be interpreted with this dynamic context in mind. The GPMC research and education agendas are broad and include high-quality prospective studies evaluating opportunistic endoscopic screening for GC/GPMC, refined delineation of what constitutes "high-risk" populations, development of novel biomarkers, alignment of best practices, implementation of training programs for improved GPMC/GC detection, and evaluation of the impact of these interventions on GC incidence and mortality in the US.

First-degree relatives of gastric cancer (GC) patients are known to have an increased risk of developing GC. However, guidelines in low-intermediate incidence regions often lack specific recommendations for managing both asymptomatic and symptomatic relatives at risk.

This study aimed to evaluate the differences in relevant histological findings (e.g. Helicobacter pylori infection, gastric precancerous and neoplastic conditions) between asymptomatic patients undergoing esophagogastroduodenoscopy due to first-degree relatives with GC and patients with symptoms or other clinical indications and presence of first-degree relatives with GC. The secondary aim was to identify the patient's risk factors of relevant histological findings.

This single-center retrospective study included patients undergoing esophagogastroduodenoscopy with biopsies with the indication for first-degree relatives with GC from January 2008 to September 2022. They were analyzed in two groups based on whether they had additional symptoms or clinical indications for esophagogastroduodenoscopy.

Overall, 283 patients were included (54.5% asymptomatic vs. 45.5% symptomatic). Histological findings that led to changes in patient management were identified in 32% of cases. No significant differences in histological findings between the two groups were observed ( P = 0.077). A subanalysis revealed that patients with male relatives affected by GC had a higher incidence of relevant histological findings than those with female family members with GC ( P = 0.013) with an odds ratio of 3.10.

First-degree relatives of GC patients may be at risk for H. pylori infection and gastric precancerous conditions regardless of symptoms or other indications, and a proactive endoscopic screening could be considered even in countries with low GC incidence.

Helicobacter pylori, Epstein-Barr virus (EBV), and human papillomavirus (HPV) are three pathogens associated with various human cancers. This study aimed to investigate the role of these pathogens in gastric cancer in a Moroccan population. A retrospective study was conducted with participants attending the Gastroenterology Department of Hassan II University Hospital in Fez. In total, 279 participants were enrolled in this study. Helicobacter pylori, EBV, and HPV were detected and genotyped using polymerase chain reaction. Significant associations have been established between H. pylori and EBV and gastric cancer. A total of 93.4% and 43.3% of gastric cancer cases were related to H. pylori and EBV, respectively (P ≤ 0.01). Helicobacter pylori-EBV co-infection was responsible for 31.6% of gastric cancer cases (P < 0.01). Correlation between pathogen genotypes and gastric cancer showed that 54.6% of gastric cancer EBV positive cases had a 30 bp deletion in the LMP1 gene, whereas 16% of gastric cancer cases had high-risk HPV genotypes (P = 0.21). These results highlight the possible role of co-infection in gastric cancer development.

Gastric cancer (GC) is a prevalent malignancy affecting the digestive system. We aimed to develop a risk prediction model based on endoscopic atrophy classification for GC.

We retrospectively collected the data from January 2020 to October 2021 in our hospital and randomly divided the patients into training and validation sets in an 8:2 ratio. We used multiple machine learning algorithms such as logistic regression (LR), Decision tree, Support Vector Machine, Random forest, and so on to establish the models. We employed the Least absolute shrinkage and selection operator (LASSO) to screen variables for the LR model. However, we chose all the variables to construct the models for other machine learning algorithms. All models were evaluated using the receiver operating characteristic curve (ROC), predictive histograms, and decision curve analysis (DCA).

A total of 1156 patients were selected for the analysis. Five variables, including age, sex, family history of GC, HP infection status, and Kimura-Takemoto Classification (KTC), were screened using LASSO analysis. The area under the curve (AUC) of all the machine learning models ranged from 0.762 to 0.974 in the training set and from 0.608 to 0.812 in the validation set. Among them, the LR model exhibited the highest AUC value (0.812, 95%CI: 0.737-0.887) in the validation set with good calibration and clinical applicability. Finally, we constructed a nomogram to demonstrate the LR model.

We established a nomogram based on endoscopic atrophy classification for GC, which might be valuable in predicting GC risk and assisting clinical decision-making.

The problem of gastric cancer (GC) prevention remains relevant for a long time. Various methods of population serological screening of atrophic gastritis and precancerous changes in the gastric mucosa have been created at present. Modern endoscopic and morphological methods of verification of the diagnosis of precancerous diseases and changes in the gastric mucosa have been introduced into the practice of gastroenterologists and oncologists. GC risk stratification systems allow the formation of risk groups that require population screening. Practical hints for population serological screening of atrophic gastritis, endoscopic and morphological verification of precancerous changes and diseases of the stomach recommend using it: When developing state programs for the prevention of stomach cancer; when implementing preventive measures for stomach cancer by doctors of all specialties; the authors also offer the possibility of use by anyone over the age of 40, provided that they seek methodological help from their doctor; in the work of health schools in any medical and preventive institutions. The use of an assessment system of certain risk factor signatures with prognostic value would add significant assistance to preventive measures against GC.

Autoimmune gastritis (AIG) is a corpus-dominant atrophic gastritis in which patients are positive for antiparietal cell antibody (APCA) and/or anti-intrinsic factor antibody. The risk of developing gastric cancer in patients with AIG remains unclear, and reliable frequency data of AIG in patients with gastric cancer are lacking.

We included 624 Korean patients with gastric tumors (612 gastric cancers and 12 neuroendocrine tumors) who had APCA results and were available for AIG evaluation. In patients with positive APCA results, endoscopy and histology findings were reviewed to diagnose AIG.

Of the 624 patients, 37 (5.9%) tested positive for APCA, and ultimately, 11 (1.8%) met the diagnostic criteria for AIG (5 both endoscopy and histology findings, 4 endoscopy-only findings, 2 histology-only findings). The frequency of AIG in patients with gastric cancer was 1.3% (8/612), and that in patients with neuroendocrine tumors was 25.0% (3/12). Of the 11 patients with AIG, serum Helicobacter pylori antibody was positive in six patients (54.5%), all of whom had gastric cancer. Histologically, three patients showed pure AIG, four patients exhibited concurrent AIG and H. pylori gastritis, and the findings for four were indefinite for AIG. The pepsinogen (PG) I levels and PG I/II ratio were significantly lower in patients with gastric cancer with AIG than in patients with gastric cancer without AIG (p=0.042 and p=0.016, respectively).

The frequency of AIG in gastric cancer patients was very low compared to that in patients with neuroendocrine tumors. Rather, concurrent AIG and H. pylori gastritis was common in patients with AIG with gastric cancer.

Although chronic atrophic gastritis (CAG), intestinal metaplasia (IM), and dysplasia constitute gastric pre-neoplastic conditions of gastric cancer (GC), data on endoscopic correlation and the prevalence in many South American countries are scarce. The aims of this study were to establish prevalence and perform endoscopic-histological correlation of gastric pre-neoplastic conditions using high-definition white light endoscopy (WLE) and to determine interobserver agreement for endoscopic findings for CAG and IM.

A prospective, observational, descriptive, cross-sectional study was carried out at a Uruguayan hospital during a 6-month period. Risk was stratified according to Operative Link for Gastritis Assessment and Operative Link for Gastric Intestinal Metaplasia stage for CAG and IM, respectively. An independent and blinded second observer was included to determine interobserver endoscopic and histologic agreement.

A total of 102 patients (mean age 57 years ± 1.6 years, 68.6% woman) were included. Prevalence of histological CAG and IM were 38.2% and IM 31.4%, respectively. Endoscopic-histological correlation for CAG had kappa index 0.063, sensitivity 46%, and specificity 60%. For endoscopic IM, the kappa index was 0.216, sensitivity 22%, and specificity 96%. Interobserver variability was good for gastric fold flattening and very good in the presence of whitish-greyish plaques for CAG and IM, respectively.

The endoscopic-histological correlation of both CAG and IM was low, raising the need for biopsy for diagnosis in all cases, regardless of HD-WLE findings. Although prevalence of gastric pre-neoplastic conditions in this group of Uruguayan patients was comparable to those described in countries with a high incidence of GC, a low proportion of high-risk stages (III and IV) was identified.

Neoadjuvant chemotherapy (NAC) has been confirmed to improve the prognosis of patients with advanced gastric cancer (AGC). However, no study has investigated whether Helicobacter pylori (HP) infection affects the postoperative survival of patients who receive NAC.

This retrospective cohort study included 307 patients with AGC who underwent laparoscopic radical gastrectomy after NAC at three hospitals in China between January 1, 2016, and April 31, 2020. Cox regression was used to assess prognostic factors for survival. Kaplan-Meier was used for survival analysis.

The HP + and the HP- group included 141 and 166 cases. The 3-year overall survival (OS) and disease-free survival (DFS) of the HP + group were significantly better than the HP- group (3-year OS: 75.9% vs. 60.2%, 3-year DFS: 70.2% vs. 52.3%; All P < 0.001). For the HP + group, ypTNM Stage III (HR, 4.00; 95% CI, 1.11-14.39; P = 0.034), NAC ≥ 4 cycles (HR, 0.43; 95% CI, 0.20-0.90; P = 0.026), and adjuvant chemotherapy (AC) ≥ 4 cycles (HR, 0.20; 95% CI, 0.09-0.48; P < 0.001) are independent prognostic factors for OS. In the cohort of HP + patients who received ≥ 4 cycles of NAC, the prognosis of patients who received ≥ 4 cycles of AC after surgery was better than that of patients who received < 4 cycles of AC (3-year OS: 92.5% vs 71.4%; P = 0.042).

Following NAC, HP + patients with AGC exhibit better prognosis than that of HP- counterparts. For potentially resectable HP + AGC patients, radical surgery following ≥ 4 cycles of NAC with ≥ 4 cycles of sequential AC might be recommended to improve survival.

Chronic atrophic gastritis (CAG) is an important stage of precancerous lesions of gastric cancer. Effective treatment and regulation of CAG are essential to prevent its progression to malignancy. Traditional Chinese medicine (TCM) has shown multi-targeted efficacy in CAG treatment, with advantages in enhancing gastric mucosal barrier defense, improving microcirculation, modulating inflammatory and immune responses, and promoting lesion healing, etc. Clinical studies and meta-analyses indicate that TCM provides significant benefits, with specific Chinese herbal compounds and monomers demonstrating protective effects on the gastric mucosa through mechanisms including anti-inflammation, anti-oxidation, and regulation of cellular proliferation and apoptosis, etc. Finally, it is pointed out that the efficacy of TCM in the treatment of CAG requires standardized research and unified standards, and constantly clarifies and improves the evaluation criteria of each dimension of gastric mucosal barrier function.

Helicobacter pylori (H. pylori), a pervasive pathobiont, colonizes the gastric mucosa and plays a crucial role in the pathogenesis of several gastroduodenal pathologies ranging from chronic gastritis to more severe disorders including peptic ulcer disease, gastric mucosa-associated lymphoid tissue lymphoma, and gastric adenocarcinoma. In symptomatic patients, endoscopy and histological examination of the gastric mucosa are the preferred tests for diagnosing H. pylori. Our study aimed to identify the frequency of H. pylori and its association with endoscopic and histopathological findings in adult Lebanese patients. Thus, 332 symptomatic adult patients, attending the Endoscopy unit of Makassed General Hospital in Beirut, were enrolled in this cross-sectional study. Overall, 14.16 % of the patients were infected with H. pylori, with male predominance. The most common endoscopic findings were gastritis and gastropathy. Moreover, H. pylori infection was significantly associated with gastric ulcers and duodenitis. On the other hand, active gastritis and chronic gastritis were the most common histopathological findings. Chronic gastritis was more frequent in H. pylori-positive patients. The association between endoscopic diagnosis and histopathological findings was then assessed. It was shown that gastropathy was significantly associated with chronic gastritis. In addition, gastric ulcer was significantly related to active gastritis and chronic gastritis. In conclusion, this study reported various endoscopic findings in H. pylori-positive patients based on the Kyoto classification. This highlights the importance of invasive diagnosis in symptomatic patients. Therefore, a combination-based approach including endoscopic and histopathological findings remains crucial in clinical practice for a definitive and accurate diagnosis of H. pylori infection and related disorders, especially in resource-limited settings.

Effective therapy against Helicobacter pylori hinges on a timely and accurate diagnosis. The objective is to assess H. pylori infection in dyspeptic patients and compare various indicative tests. After approval, gastrointestinal biopsies and blood samples of 96 subjects exhibiting gastroduodenal symptoms were collected; both invasive and non-invasive tests were employed to analyse the samples. Results revealed 40 cases (41.67%) positive for H. pylori via histopathology and rapid urease testing, while 46 subjects tested positive for IgA and IgG antibodies via ELISA. Eighteen biopsies showed positivity in the culture test, corroborated by endoscopic examination and biochemical assessments (urease, catalase and oxidase). The isolates showed various degrees of resistance to antibiotics, while polymyxin B showed the highest (100%) followed by amoxicillin (88.90%) and kanamycin (77.78%). Additionally, the CagA gene presence was detected in 18 individuals through molecular methods. Sensitivity and specificity percentages (%) varied among diagnostic methods: histopathology (95/77), rapid urease (100/83.5), gram staining (85.7/90), IgG serology (100/66.6), IgA serology (100/79.5), PCR (100/75), RUT and IgG serology combination (100/79.04), and RUT, Gram staining and IgG serology combination (100/92.4), respectively. PCR emerged as the most reliable test. In the current investigation, other tests also exhibited high sensitivity and specificity values. Thus, employing comparative detection methods rather than relying solely on one methodology is advisable for accurate detection.

Helicobacter pylori infection is a significant contributing factor of gastric cancer. Metachronous neoplasms also pose a risk. The mechanism underlying the impact of H. pylori eradication on preventing metachronous gastric cancer is unclear. This study aimed to investigate immunity changes in gastric mucosa after H. pylori eradication and to identify mechanisms preventing metachronous recurrence.

Patients diagnosed with gastric neoplasm and H. pylori infection, who underwent endoscopic resection, were included. Thirty-six cases of metachronous neoplasms occurring after eradication (metachronous group) were compared to 36 controls matched for age, sex, atrophy, and metaplasia (control group). Histological features and immunohistochemical staining for T-cell (CD3, CD4, and CD8) and immune exhaustion (forkhead/winged helix transcription factor and programmed cell death-ligand 1) markers in the non-tumor-bearing mucosa were evaluated.

In histologic features, glandular atrophy and intestinal metaplasia in the gastric mucosa significantly improved following H. pylori eradication in the control group (p < 0.001, 0.008), whereas they did not improve in the metachronous group (p = 0.449, 0.609). CD8 and CD8/CD3 ratios increased in the control group (p < 0.001, 0.04), but did not show differences in the metachronous group (p = 0.057, 0.245). The CD4/CD3 ratio and programmed cell death-ligand 1/CD4 expression significantly decreased after H. pylori eradication in the control group (p = 0.003, 0.042), but not in the metachronous group (p = 0.54, 0.55).

This observational study suggests that H. pylori eradication may prevent the recurrence of gastric neoplasia by improving histological inflammation and overcoming immune exhaustion.

Gastric cancer precursors demonstrate highly-variable rates of progression toward neoplasia. Certain high-risk precursors, such as gastric intestinal metaplasia with advanced histologic features, may be at up to 30-fold increased risk for progression compared to lower-risk intestinal metaplasia. The biological differences between high- and low-risk lesions have been incompletely explored. In this study, we use several clinical cohorts to characterize the microenvironment of advanced gastric cancer precursors relative to low-risk lesions using bulk, spatial, and single-cell gene expression assays. We identified a 26-gene panel which is associated with advanced lesions, localizes to metaplastic glands on histopathology, and is expressed in aberrant mature and immature intestinal cells not normally present in the healthy stomach. This gene expression signature suggests an important role of the immature intestinal lineages in promoting carcinogenesis in the metaplastic microenvironment. These findings may help to inform future biomarker development and strategies of gastric cancer prevention.

The pathogenesis of non-ampullary duodenal epithelial tumors (NADETs) is not fully understood. NADETs that express gastric-type mucin phenotypes (G-NADETs) are noteworthy because of their high malignancy. Gastric foveolar metaplasia, from which G-NADETs originate, protects the duodenal mucosa from gastric acidity. As gastric acid secretion is affected by endoscopic gastric mucosal atrophy (EGMA), we hypothesized that EGMA would be associated with G-NADETs.

To evaluate the association between EGMA and the occurrence of G-NADETs.

This cross-sectional retrospective study investigated the relationship between EGMA and NADETs in 134 patients. The duodenum was divided into parts 1 (bulb), 2 (superior duodenal angle to the papilla), and 3 (anal side of the papilla to the horizontal part). The effects of gastric acidity and presence of Brunner's glands were considered. EGMA was divided into types C (no or mild atrophy) and O (severe atrophy). Mucin phenotype expressions in NADETs were divided into gastric, intestinal, gastrointestinal, and unclassifiable.

When NADETs were classified according to EGMA, 105 were classified as type C and 29 as type O. G-NADETs were present in 11.9% (16 cases) of all cases, and all 16 cases were of type C. Among G-NADETs, 93.8% (15 cases) were present in part 1 or 2. There was an association between G-NADETs and type C in part 1, and 50.0% (eight of 16 cases) of G-NADETs were associated with a current or previous Helicobacter pylori infection status. Additionally, all eight cases occurred in part 1.

G-NADETs were significantly associated with type C. Gastric acidity and Brunner's gland growth may be associated with G-NADETs.

Clinical practice guidelines (CPGs) are intended to offer appropriate recommendations for clinical practice based on the available evidence while acknowledging existing gaps and uncertainties. The quality of CPGs for gastric precancerous lesions (GPL), distribution of evidence quality, and strength of recommendations are unknown.

Systematically evaluate the quality of CPGs for GPL and identify areas for improvement in the development process.

PubMed, Embase, Cochrane Library, Cumulative Index to Nursing and Allied Health Literature, and six online CPG repositories were systematically searched for CPGs related to GPL. Three researchers independently assessed the methodological quality of the included CPGs by using the AGREE II tool. The reporting and recommendation quality of the CPGs were evaluated using the RIGHT and AGREE-REX tools through consensus. Evidence-based CPGs were analyzed using the Grading of Recommendation Assessment, Development, and Evaluation system to determine the distribution of quality of evidence and strength of recommendations.

A total of 4046 records were identified; nine CPGs met the eligibility criteria for this study. The mean overall score for the methodological quality of the CPGs was 46.22%. Among the six domains, the mean score for clarity of presentation was the highest (71.67%), while the mean score for applicability was the lowest (24.56%). Among the nine CPGs, only one was considered high quality. Regarding reporting quality, domains 1, 3, and 4 had mean reporting rates equal to or higher than 60%. The mean overall score for the recommendation quality was 19.11%. In total, 235 recommendations were identified through the screening process, of which 64.4% were classified as strong. However, only 17.5% of the strong recommendations were supported by high-quality evidence.

The overall quality of CPGs for GPL was poor, with uneven quality across domains. In addition, the consistency between the strength of recommendations and the quality of evidence was poor.

Helicobacter pylori infects at least half the population worldwide, and its highly diverse genomic content correlates with its geographic distribution because of its prolonged relationship with humans. The extremely low infection prevalence alongside low inflammation severity observed in some countries might be caused by strains with low virulence potential. Therefore, this study aimed to investigate whole-genome analysis datasets of Sri Lankan H. pylori strains. H. pylori strains were isolated from biopsy specimens and underwent whole-genome sequencing to investigate their antibiotic resistance and virulence potential. The prevalence of H. pylori infection in Sri Lanka is extremely low (1.7% in a previous study), and only six H. pylori strains were successfully isolated from bacterial culture. Antibiotic resistance analysis showed a high prevalence of metronidazole resistance (83.3%, five out of six strains), and investigation of the related genes showed truncation of the rdxA and frxA genes and single-nucleotide polymorphisms in the rdxA, frxA, ribF, omp11, and fur genes. Most virulence genes of the 144 assessed were present, except for the cag pathogenicity island (cagPAI) (absent in four out of six strains), babA/B/C, and tlpB genes. An incomplete type 4 secretion system (tfs) was found in three strains. A pan-genome analysis with non-Sri Lankan H. pylori strains showed that the htpX gene was found only in Sri Lankan strains (p-corrected = 0.0008). A phylogenetic analysis showed that the Sri Lankan strains clustered with strains from hpAsia2 and hpEurope. This comparative genomic study shows that H. pylori strains with low virulence potential are present in countries with a low prevalence of infection and disease severity, indicating a strain-type geographical pattern. The tailored guidelines for screening and treatment strategy for each region are necessary to obtain effective and efficient eradication.