A mechanistic study of Anwei decoction intervention in a rat model of gastric intestinal metaplasia through the endoplasmic reticulum stress - Autophagy pathway.

OBJECTIVE: To investigate the mechanism of Anwei decoction (AWD) intervention on gastric intestinal metaplasia (GIM) using a rat model through the endoplasmic reticulum stress-autophagy pathway. METHODS: Gastric intestinal metaplasia was induced in rats using 1-methyl-3-nitro-1-nitrosoguanidine. The experiment included a normal control group, a model group, and low-, medium- and high-dose AWD groups. The specificity of intestinal epithelial cells was determined for model establishment and drug efficacy by detecting the protein expression of markers such as MUC2, VILLIN and CDX2 through western blotting (WB). The effects of AWD on endoplasmic reticulum stress and autophagy were evaluated by measuring the mRNA and protein expression levels of endoplasmic reticulum stress markers (PEPK, ATF6, CHOP and caspase-12) and autophagy markers (LC3Ⅱ and Beclin-1) using reverse transcription polymerase chain reaction and the WB method. Furthermore, the ultrastructure of gastric mucosal cells and autophagosome status were observed using transmission electron microscopy. RESULTS: Compared with the model group, the AWD-treated rats exhibited significant improvement in body weight (P < 0.01), reduced protein expression of the intestine epithelial cell-specific markers MUC2, VILLIN, CDX2 and KLF4 (P < 0.01 for all) and increased SOX2 protein expression (P < 0.01). In addition, AWD suppressed the mRNA and protein expression of endoplasmic reticulum stress markers PEPK and ATF6 (P < 0.01 for all) and promoted the mRNA and protein expression of autophagy and apoptosis markers CHOP, caspase-12, LC3Ⅱ and Beclin-1 (P < 0.01 for all). CONCLUSION: Anwei decoction effectively inhibits the further progression of GIM and prevents the occurrence of gastric mucosal carcinogenesis.

A deep learning model based on magnifying endoscopy with narrow-band imaging to evaluate intestinal metaplasia grading and OLGIM staging: A multicenter study.

BACKGROUND AND PURPOSE: Patients with stage III or IV of operative link for gastric intestinal metaplasia assessment (OLGIM) are at a higher risk of gastric cancer (GC). We aimed to construct a deep learning (DL) model based on magnifying endoscopy with narrow-band imaging (ME-NBI) to evaluate OLGIM staging. METHODS: This study included 4473 ME-NBI images obtained from 803 patients at three endoscopy centres. The endoscopic expert marked intestinal metaplasia (IM) regions on endoscopic images of the target biopsy sites. Faster Region-Convolutional Neural Network model was used to grade IM lesions and predict OLGIM staging. RESULTS: The diagnostic performance of the model for IM grading in internal and external validation sets, as measured by the area under the curve (AUC), was 0.872 and 0.803, respectively. The accuracy of this model in predicting the high-risk stage of OLGIM was 84.0%, which was not statistically different from that of three junior (71.3%, p = 0.148) and three senior endoscopists (75.3%, p = 0.317) specially trained in endoscopic images corresponding to pathological IM grade, but higher than that of three untrained junior endoscopists (64.0%, p = 0.023). CONCLUSION: This DL model can assist endoscopists in predicting OLGIM staging using ME-NBI without biopsy, thereby facilitating screening high-risk patients for GC.

Low prevalence of gastric intestinal metaplasia and Helicobacter pylori on surveillance upper endoscopy in Lynch syndrome.

Lynch syndrome (LS) increases the risk of numerous different cancers including gastric cancer. While some current guidelines recommend empiric gastric biopsies be performed during upper gastrointestinal cancer surveillance in Lynch syndrome (LS), the yield of these biopsies and the prevalence of gastric intestinal metaplasia (GIM) and Helicobacter pylori (HP) in LS remains unknown. Herein we analyze 165 consecutive individuals with LS who underwent upper endoscopic surveillance with biopsies of the gastric antrum and body being performed universally in all individuals. Of the study cohort, 6.7% of universally biopsied individuals with LS had GIM and/or HP (5.5% GIM, 3.6% HP). Biopsies of the gastric body did not increase rates of GIM/HP identification compared to antral biopsies alone. GIM was detected on subsequent surveillance in 2.2% of individuals without prior GIM, which may represent either newly developed GIM or GIM that was missed on a prior upper endoscopy due to sampling error. These findings support inclusion of at least baseline gastric antrum biopsies as a routine component of all standard surveillance upper endoscopies performed in LS.

Evolving Concepts in Helicobacter pylori Management.

Helicobacter pylori is the most common chronic bacterial infection worldwide and the most significant risk factor for gastric cancer, which remains a leading cause of cancer-related death globally. H pylori and gastric cancer continue to disproportionately impact racial and ethnic minority and immigrant groups in the United States. The approach to H pylori case-finding thus far has relied on opportunistic testing based on symptoms or high-risk indicators, such as racial or ethnic background and family history. However, this approach misses a substantial proportion of individuals infected with H pylori who remain at risk for gastric cancer because most infections remain clinically silent. Moreover, individuals with chronic H pylori infection are at risk for gastric preneoplastic lesions, which are also asymptomatic and only reliably diagnosed using endoscopy and biopsy. Thus, to make a significant impact in gastric cancer prevention, a systematic approach is needed to better identify individuals at highest risk of both H pylori infection and its complications, including gastric preneoplasia and cancer. The approach to H pylori eradication must also be optimized given sharply decreasing rates of successful eradication with commonly used therapies and increasing antimicrobial resistance. With growing acceptance that H pylori should be managed as an infectious disease and the increasing availability of susceptibility testing, we now have the momentum to abandon empirical therapies demonstrated to have inadequate eradication rates. Molecular-based susceptibility profiling facilitates selection of a personalized eradication regimen without necessitating an invasive procedure. An improved approach to H pylori eradication coupled with population-level programs for screening and treatment could be an effective and efficient strategy to prevent gastric cancer, especially in minority and potentially marginalized populations that bear the heaviest burden of H pylori infection and its complications.

The Clinical Impact and Cost-Effectiveness of Surveillance of Incidentally Detected Gastric Intestinal Metaplasia: A Microsimulation Analysis.

BACKGROUND & AIMS: Gastric intestinal metaplasia (GIM) is associated with a higher risk of noncardia intestinal gastric adenocarcinoma (GA). The aim of this study was to estimate lifetime benefits, complications, and cost-effectiveness of GIM surveillance using esophagogastroduodenoscopy (EGD). METHODS: We developed a semi-Markov microsimulation model of patients with incidentally detected GIM, to compare the effectiveness of EGD surveillance with no surveillance at 10-year, 5-year, 3-year, 2-year, and 1-year intervals. We modeled a simulated cohort of 1,000,000 US individuals aged 50 with incidental GIM. Outcome measures were lifetime GA incidence, mortality, number of EGDs, complications, undiscounted life-years gained, and incremental cost-effectiveness ratio with a willingness-to-pay threshold of $100,000/quality-adjusted life-year (QALY). RESULTS: In the absence of surveillance, the model simulated 32.0 lifetime GA cases and 23.0 lifetime GA deaths per 1000 individuals with GIM, respectively. Among surveilled individuals, simulated lifetime GA incidence (per 1000) decreased with shorter surveillance intervals (10-year to 1-year, 11.2-6.1) as did GA mortality (7.4-3.6). Compared with no surveillance, all modeled surveillance intervals yielded greater life expectancy (87-190 undiscounted life-years gained per 1000); 5-year surveillance provided the greatest number of life-years gained per EGD performed and was the cost-effective strategy ($40,706/QALY). In individuals with risk factors of family history of GA or anatomically extensive, incomplete-type GIM intensified 3-year surveillance was cost-effective (incremental cost-effectiveness ratio $28,156/QALY and $87,020/QALY, respectively). CONCLUSIONS: Using microsimulation modeling, surveillance of incidentally detected GIM every 5 years is associated with reduced GA incidence/mortality and is cost-effective from a health care sector perspective. Real-world studies evaluating the impact of GIM surveillance on GA incidence and mortality in the United States are needed.

Diagnosing and grading gastric atrophy and intestinal metaplasia using semi-supervised deep learning on pathological images: development and validation study.

OBJECTIVE: Patients with gastric atrophy and intestinal metaplasia (IM) were at risk for gastric cancer, necessitating an accurate risk assessment. We aimed to establish and validate a diagnostic approach for gastric biopsy specimens using deep learning and OLGA/OLGIM for individual gastric cancer risk classification. METHODS: In this study, we prospectively enrolled 545 patients suspected of atrophic gastritis during endoscopy from 13 tertiary hospitals between December 22, 2017, to September 25, 2020, with a total of 2725 whole-slide images (WSIs). Patients were randomly divided into a training set (n = 349), an internal validation set (n = 87), and an external validation set (n = 109). Sixty patients from the external validation set were randomly selected and divided into two groups for an observer study, one with the assistance of algorithm results and the other without. We proposed a semi-supervised deep learning algorithm to diagnose and grade IM and atrophy, and we compared it with the assessments of 10 pathologists. The model's performance was evaluated based on the area under the curve (AUC), sensitivity, specificity, and weighted kappa value. RESULTS: The algorithm, named GasMIL, was established and demonstrated encouraging performance in diagnosing IM (AUC 0.884, 95% CI 0.862-0.902) and atrophy (AUC 0.877, 95% CI 0.855-0.897) in the external test set. In the observer study, GasMIL achieved an 80% sensitivity, 85% specificity, a weighted kappa value of 0.61, and an AUC of 0.953, surpassing the performance of all ten pathologists in diagnosing atrophy. Among the 10 pathologists, GasMIL's AUC ranked second in OLGA (0.729, 95% CI 0.625-0.833) and fifth in OLGIM (0.792, 95% CI 0.688-0.896). With the assistance of GasMIL, pathologists demonstrated improved AUC (p = 0.013), sensitivity (p = 0.014), and weighted kappa (p = 0.016) in diagnosing IM, and improved specificity (p = 0.007) in diagnosing atrophy compared to pathologists working alone. CONCLUSION: GasMIL shows the best overall performance in diagnosing IM and atrophy when compared to pathologists, significantly enhancing their diagnostic capabilities.

Modified Chaishao Liujunzi Decoction inhibits bile acid-induced gastric intestinal metaplasia: from network prediction to experimental verification.

Modified Chaishao Liujunzi Decoction (MCLD) is a traditional Chinese medicine formula that is used mainly to improve clinical symptoms, alleviate gastric mucosal inflammation, and improve gastric mucosal lesions in patients with gastric intestinal metaplasia (GIM). GIM is considered a precancerous gastric cancer (GC) lesion (PLGC) and exploring effective intervention measures for GIM is of great importance for the prevention of GC. The purpose of this study was to reveal the potential molecular mechanism of MCLD in improving GIM induced by bile acid (BA) using network pharmacology and experimental validation. Through network pharmacology, we speculated that MCLD could act on GIM by driving the epidermal growth factor receptor (EGFR)/PI3K/AKT/mammalian target of rapamycin (mTOR) pathway. After that, we used deoxycholic acid (DCA) to treat GES-1 cells to simulate BA-induced GIM and observed the effects of MCLD treatment. The results indicate that MCLD can significantly inhibit DCA-induced cell proliferation and down-regulate the expression of pro-inflammatory cytokines and intestinal-specific markers. At the same time, MCLD also negatively regulated the expression of genes and proteins of the EGFR/PI3K/AKT/mTOR pathway. Combination with EGFR agonists and inhibitors suggested that MCLD may improve GIM by inhibiting the EGFR/PI3K/AKT/mTOR pathway, which may be related to its inhibition of DCA-induced cell proliferation through this pathway. In conclusion, MCLD may improve BA-induced GIM through the EGFR/PI3K/AKT/mTOR pathway, as predicted by network pharmacology, and is a potential Chinese medicine prescription for the treatment or reversal of GIM.

Association between country of birth and gastric intestinal metaplasia: a retrospective cohort study.

Background: As a precursor to gastric cancer, gastric intestinal metaplasia (GIM) represents a target for surveillance. US-based guidelines recommend surveillance of racial/ethnic minorities and immigrants from high incidence gastric cancer regions, yet there is marked variability in prevalence amongst these subgroups and within groups from high incidence regions. There is a paucity of information regarding country of birth as a risk factor for GIM and we sought to determine the association between country of birth and GIM in an ethnically and racially diverse US population. Methods: This was a retrospective cohort study of persons who underwent esophagogastroduodenoscopy (EGD) with gastric biopsy at University of Miami Hospital between 2011 and 2021. A natural language processing (NLP) algorithm was developed and implemented to extract diagnoses of GIM and Helicobacter pylori (HP) infection from endoscopic pathology reports. Multivariable logistic regression was performed to evaluate risk factors for GIM, accounting for important covariates, including country of birth. Findings: A total of 21,108 persons from 130 varying countries of birth were included in the study. A total of 1699 cases of GIM were identified yielding a prevalence of 8.0% (95% CI: 7.7-8.4%). Multivariable analysis was restricted to countries with at least 100 persons in the cohort, yielding 15 countries with 1208 cases of GIM. Country of birth (p < 0.0001), race/ethnicity (p = 0.026), active HP infection (p < 0.0001), and increasing age (p < 0.0001) were significantly associated with increased odds of GIM. Highest odds for GIM were among persons born in Ecuador (OR 2.34, 95% CI 1.56-3.50), Honduras (OR 2.34, 95% CI 1.65-3.34), and Peru (OR 2.17, 95% CI 1.58-2.99). Interpretation: We demonstrate that country of birth is a key risk factor for GIM. Not all countries that are thought to be in "high-risk" regions are associated with higher rates of GIM, underlining the importance of studying the under-investigated risk factor of country of birth. Guidelines should account for country of birth, in addition to other risk factors, to tailor screening/surveillance appropriately. Funding: Shida Haghighat, MD, MPH is supported by an NIH training grant T32 DK 11667805.

Intestinal Metaplasia Associated with Symptoms of Dyspepsia.

Background: Peptic ulcer disease (PUD) and Helicobacter pylori (HP) are associated with dyspepsia, but the role of gastric intestinal metaplasia (IM) has not been described. The objective of this study is to examine the association between gastric IM and dyspepsia. Methods: We developed a cohort of consecutive patients referred to gastroenterology between Jan 2019 and July 2020 for dyspepsia and iron deficiency anemia (IDA) and completed an upper endoscopy with biopsies in a safety-net health system. The primary outcome was the prevalence of gastric IM in patients with dyspepsia compared to IDA. Secondary outcomes included prevalence of HP, chronic gastritis (CG) and chronic active gastritis (CAG) in the dyspepsia and IDA groups. A multivariable analysis was performed to assess the independent association between gastric IM and dyspepsia. Results: Compared to the IDA cohort (n = 366), patients with dyspepsia (n = 349) were more likely to be female (65% vs. 47%, p < 0.01), harbor gastric IM (20.3% vs. 14.2%, p = 0.03), and less likely to have CAG (12.0% vs. 26.5%, p < 0.01) or HP (10.9% vs. 21.3%, p < 0.01). After adjusting for pathological findings, race, ethnicity, gender and age, the association strengthened between IM and dyspepsia (adj OR 1.81 from OR 1.54, 95% CI 1.19-2.76, p < 0.01). Conclusions: We observed a significant relationship between the presence of gastric IM and dyspepsia symptoms, which increased after adjusting for confounding factors. Future studies should verify the relationship between IM and dyspepsia, the effect of IM regression, and possible mediators of gastric IM on symptoms.

Endoscopic screening and surveillance for gastric cancer: challenges and opportunities.

Endoscopic screening is premised on the detection of pre-symptomatic, early-stage gastric neoplasia that enables curative resection. Endoscopic screening reduces gastric cancer mortality in high-incidence countries but is highly resource-intensive. Endoscopic surveillance of high-risk subgroups of intestinal metaplasia has gained traction in low and intermediate-incidence countries, and emerging evidence suggests that risk-stratified endoscopic surveillance may facilitate timely detection of cancer. However, outcome-based evidence is required to support its adoption. Yet the impact of an endoscopy-based strategy may well lie in heralding a paradigm that regards every routine diagnostic gastroscopy as an opportunity to screen for GC. Endoscopic surveillance also renders gastric intestinal metaplasia a de facto disease, and the ramification of this needs to be further elucidated.

Clinical features of gastric adenoma detected within 3 years after negative screening endoscopy in Korea.

Background: Early detection and management of gastric adenoma are important for preventing gastric cancer. The present study aimed to evaluate the predictors of missed gastric adenoma on screening endoscopy in Korea and identify the risk factors associated with interval precancerous gastric lesions. Methods: All cases of gastric adenomas diagnosed via screening endoscopy between 2007 and 2019 were reviewed. Among them, those who had undergone endoscopy within 3 years were included in the present study. Missed gastric adenoma was defined as gastric adenoma diagnosed within 3 years after negative screening endoscopy. Results: In total, 295 cases of gastric adenoma were identified. Of these, 95 (32.2%) were missed gastric adenoma cases (mean age, 60.6 years; average interval between final and index endoscopies, 12.6 months); the remaining 200 (67.8%) were newly detected adenoma cases. Univariate analysis revealed that male sex, endoscopist experience, observation time, and presence of gastric intestinal metaplasia (pathologically proven) were associated with missed gastric adenoma. Multivariate analysis revealed that gastric intestinal metaplasia (odds ratio [OR], 2.736; 95% confidence interval [CI], 1.320-5.667; P = 0.007) and shorter observation time of the index screening endoscopy (B, -0.011; OR, 0.990; 95% CI, 0.986-0.993; P < 0.001) were independent risk factors for missed gastric adenoma. The optimal cut-off for the observation time for detecting gastric adenoma was 3.53 minutes (area under curve, 0.738; 95% CI, 0.677-0.799; P < 0.001). Conclusions: Gastric intestinal metaplasia is an indication of missed gastric adenoma. Therefore, careful inspection of gastric mucosa with gastric intestinal metaplasia and proper observation time can lower the possibility of missing the gastric adenoma during screening.

Goblet cells segmentation from confocal laser endomicroscopy with an improved U-Net.

Gastric intestinal metaplasia (GIM) is regarded as a remarkable precursor for the development of intestinal-type stomach cancer. Goblet cell (GC) segmentation is the crucial step for assessing the degree of GIM by confocal laser endomicroscopy (CLE). However, GC segmentation by hand is difficult, unreliable, and time-consuming. Meanwhile, due to the high resolution and noise interference of CLE images, existing segmentation approaches perform poorly on this task. To tackle those issues, we collected 343 confocal laser endomicroscopy images of 62 patients from a Grade-A tertiary hospital. Each CLE image is manually annotated and then verified three times by skilled medical specialists. Then, U-Net is improved by incorporating the pixel gradient attention mechanism, which focuses on color gradient information around GC and captures color gradient features to direct feature maps in the skip connection layer. At last, the model output vector is used to calculate the possibility map and generate the final segmentation area. Compared with mainstream models, our proposed GC segmentation method from CLE with an improved U-Net (GCSCLE) performs the better segmentation result when tested on our CLE dataset and achieved an IOU of 87.95% and a DICE of 86.64%. Our result shows, the performance of the GCSCLE can be compared with the manual CLE image processing in clinical settings, and it can improve segmentation accuracy and save time and costs.

Helicobacter pylori promotes gastric intestinal metaplasia through activation of IRF3-mediated kynurenine pathway.

BACKGROUND: Metabolic reprogramming is a critical event for cell fate and function, making it an attractive target for clinical therapy. The function of metabolic reprogramming in Helicobacter pylori (H. pylori)-infected gastric intestinal metaplasia remained to be identified. METHODS: Xanthurenic acid (XA) was measured in gastric cancer cells treated with H. pylori or H. pylori virulence factor, respectively, and qPCR and WB were performed to detect CDX2 and key metabolic enzymes expression. A subcellular fractionation approach, luciferase and ChIP combined with immunofluorescence were applied to reveal the mechanism underlying H. pylori mediated kynurenine pathway in intestinal metaplasia in vivo and in vitro. RESULTS: Herein, we, for the first time, demonstrated that H. pylori contributed to gastric intestinal metaplasia characterized by enhanced Caudal-related homeobox transcription factor-2 (CDX2) and mucin2 (MUC2) expression, which was attributed to activation of kynurenine pathway. H. pylori promoted kynurenine aminotransferase II (KAT2)-mediated kynurenine pathway of tryptophan metabolism, leading to XA production, which further induced CDX2 expression in gastric epithelial cells. Mechanically, H. pylori activated cyclic guanylate adenylate synthase (cGAS)-interferon regulatory factor 3 (IRF3) pathway in gastric epithelial cells, leading to enhance IRF3 nuclear translocation and the binding of IRF3 to KAT2 promoter. Inhibition of KAT2 could significantly reverse the effect of H. pylori on CDX2 expression. Also, the rescue phenomenon was observed in gastric epithelial cells treated with H. pylori after IRF3 inhibition in vitro and in vivo. Most importantly, phospho-IRF3 was confirmed to be a clinical positive relationship with CDX2. CONCLUSION: These finding suggested H. pylori contributed to gastric intestinal metaplasia through KAT2-mediated kynurenine pathway of tryptophan metabolism via cGAS-IRF3 signaling, targeting the kynurenine pathway could be a promising strategy to prevent gastric intestinal metaplasia caused by H. pylori infection. Video Abstract.

Alteration of gastric microbiota and transcriptome in a rat with gastric intestinal metaplasia induced by deoxycholic acid.

Objective: Bile reflux plays a key role in the development of gastric intestinal metaplasia (GIM), an independent risk factor of gastric cancer. Here, we aimed to explore the biological mechanism of GIM induced by bile reflux in a rat model. Methods: Rats were treated with 2% sodium salicylate and allowed to freely drink 20 mmol/L sodium deoxycholate for 12 weeks, and GIM was confirmed by histopathological analysis. Gastric microbiota was profiled according to the 16S rDNA V3-V4 region, gastric transcriptome was sequenced, and serum bile acids (BAs) were analyzed by targeted metabolomics. Spearman's correlation analysis was used in constructing the network among gastric microbiota, serum BAs, and gene profiles. Real-time polymerase chain reaction (RT-PCR) measured the expression levels of nine genes in the gastric transcriptome. Results: In the stomach, deoxycholic acid (DCA) decreased the microbial diversity but promoted the abundances of several bacterial genera, such as Limosilactobacillus, Burkholderia-Caballeronia-Paraburkholderia, and Rikenellaceae RC9 gut group. Gastric transcriptome showed that the genes enriched in gastric acid secretion were significantly downregulated, whereas the genes enriched in fat digestion and absorption were obviously upregulated in GIM rats. The GIM rats had four promoted serum BAs, namely cholic acid (CA), DCA, taurocholic acid, and taurodeoxycholic acid. Further correlation analysis showed that the Rikenellaceae RC9 gut group was significantly positively correlated with DCA and RGD1311575 (capping protein-inhibiting regulator of actin dynamics), and RGD1311575 was positively correlated with Fabp1 (fatty acid-binding protein, liver), a key gene involved in fat digestion and absorption. Finally, the upregulated expression of Dgat1 (diacylglycerol acyltransferase 1) and Fabp1 related to fat digestion and absorption was identified by RT-PCR and IHC. Conclusion: DCA-induced GIM enhanced gastric fat digestion and absorption function and impaired gastric acid secretion function. The DCA-Rikenellaceae RC9 gut group-RGD1311575/Fabp1 axis might play a key role in the mechanism of bile reflux-related GIM.

Diagnostic validity and learning curve of non-NBI expert endoscopists in gastric intestinal metaplasia diagnosis.

BACKGROUND: Endoscopists' experience influences narrow-band imaging (NBI)-guided gastric intestinal metaplasia (GIM) diagnostic performance. We aimed to evaluate the general gastroenterologists (GE) performance in NBI-guided GIM diagnosis compared to NBI experts (XP) and assess GEs' learning curve. METHODS: A cross-sectional study was conducted between 10/2019 and 2/2022. Histology-proven GIM who underwent esophagogastroduodenoscopy (EGD) were randomly assessed by 2XPs or 3GEs. Endoscopists' performance on NBI-guided diagnoses were compared to the pathological diagnosis (gold standard) in five areas of the stomach according to the Sydney protocol. The primary outcome were GIM diagnosis validity scores of GEs compared to XPs. The secondary outcome was the minimum number of lesions required for GEs to achieve an accuracy of GIM diagnosis ≥ 80%. RESULTS: One thousand one hundred and fifty-five lesions from 189 patients (51.3% male, mean age 66 ± 10 years) were examined. GEs performed EGD in 128 patients with 690 lesions. the GIM diagnosis sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of GEs compared to the XPs, were 91% vs.93%, 73% vs.83%, 79% vs.83%, 89% vs.93%, and 83% vs.88%, respectively. GEs demonstrated lower specificity (mean difference - 9.4%; 95%CI - 16.3, 1.4; p = 0.008) and accuracy (mean difference - 5.1%; 95%CI - 3.3, 6.3; p = 0.006) compared to XPs. After 100 lesions (50% GIM), GEs achieved an accuracy of ≥ 80% and all diagnostic validity scores were comparable to the XPs (p < 0.05 all). CONCLUSIONS: Compared to XPs, GEs had lower specificity and accuracy for GIM diagnosis. The learning curve for a GE to achieve comparable performance to XPs would necessitate at least 50 GIM lesions. Created with BioRender.com.

Current role of narrow band imaging in diagnosing gastric intestinal metaplasia: a systematic review and meta-analysis of its diagnostic accuracy.

Background: Gastric intestinal metaplasia (GIM) can be missed by random gastric biopsies taken during white light endoscopy. Narrow band imaging (NBI) may potentially improve the detection of GIM. However, pooled estimates from prospective studies are lacking and the diagnostic accuracy of NBI in detecting GIM needs to be more precisely defined. The aim of this systematic review and meta-analysis was to study the diagnostic performance of NBI in detecting GIM. Methods: PubMed/Medline and EMBASE were screened for studies examining GIM in relation to NBI. Data from each study were extracted and calculations of pooled sensitivity, specificity, likelihood ratios, diagnostic odds ratios (DORs), and areas under the curve (AUCs) were performed. Fixed or random effects models, were used as appropriate, depending on the presence of significant heterogeneity. Results: We included 11 eligible studies in the meta-analysis, comprising 1672 patients. NBI showed a pooled sensitivity of 80% (95% confidence interval [CI] 69-87), specificity of 93% (95%CI 85-97), DOR 48 (95%CI 20-121), and AUC of 0.93 (95%CI 0.91-0.95) in detecting GIM. Conclusions: This meta-analysis showed that NBI is a reliable endoscopic means of detecting GIM. NBI with magnification performed better than NBI without magnification. However, better designed prospective studies are needed to precisely determine the diagnostic role of NBI, especially in high-risk populations where early detection of GIM can impact gastric cancer prevention and survival.

Methylene blue chromoendoscopy is more useful in detection of intestinal metaplasia in the stomach than mucosal pit pattern or vessel evaluation and predicts advanced Operative Link on Gastric Intestinal Metaplasia stages.

BACKGROUND/AIMS: Intestinal metaplasia (IM) of the stomach is a precancerous condition that is often not visible during conventional endoscopy. Hence, we evaluated the utility of magnification endoscopy and methylene blue (MB) chromoendoscopy to detect IM. METHODS: We estimated the percentage of gastric mucosa surface staining with MB, mucosal pit pattern, and vessel visibility and correlated it with the presence of IM and the percentage of metaplastic cells in histology, similar to the Operative Link on Gastric Intestinal Metaplasia (OLGIM) stage. RESULTS: IM was found in 25 of 33 (75.8%) patients and in 61 of 135 biopsies (45.2%). IM correlated with positive MB staining (p<0.001) and other than dot pit patterns (p=0.015). MB staining indicated IM with better accuracy than the pit pattern or vessel evaluation (71.7% vs. 60.5% and 49.6%, respectively). At a cut-off point of 16.5% for the MB-stained gastric surface, the sensitivity, specificity, and accuracy of chromoendoscopy in the detection of advanced OLGIM stages were 88.9%, 91.7%, and 90.9%, respectively. The percentage of metaplastic cells detected on histology was the strongest predictor of positive MB staining. CONCLUSION: MB chromoendoscopy can serve as a screening method for detecting advanced OLGIM stages. MB mainly stains IM areas with a high concentration of metaplastic cells.

Real-time gastric intestinal metaplasia diagnosis tailored for bias and noisy-labeled data with multiple endoscopic imaging.

This work presents real-time segmentation viz. gastric intestinal metaplasia (GIM). Recently, GIM segmentation of endoscopic images has been carried out to differentiate GIM from a healthy stomach. However, real-time detection is difficult to achieve. Conditions are challenging, and include multiple color modes (white light endoscopy and narrow-band imaging), other abnormal lesions (erosion and ulcer), noisy labels etc. Herein, our model is based on BiSeNet and can overcome the many issues regarding GIM. Application of auxiliary head and additional loss are seen to improve performance as well as enhance multiple color modes accurately. Further, multiple pre-processing techniques are utilized for leveraging detection performance: namely, location-wise negative sampling, jigsaw augmentation, and label smoothing. Finally, the decision threshold can be adjusted separately for each color mode. Work undertaken at King Chulalongkorn Memorial Hospital examined 940 histologically proven GIM images and 1239 non-GIM images, obtained over 173 frames per second (FPS). In terms of accuracy, our model is seen to outperform all baselines. Our results demonstrate sensitivity, specificity, positive predictive, negative predictive, accuracy, and mean intersection over union (IoU), achieving GIM segmentation values of 91%, 96%, 91%, 91%, 96%, and 55%, respectively.

Linked Color Imaging for Stomach.

Image-enhanced endoscopy (IEE) plays an important role in the detection and further examination of gastritis and early gastric cancer (EGC). Linked color imaging (LCI) is also useful for detecting and evaluating gastritis, gastric intestinal metaplasia as a pre-cancerous lesion, and EGC. LCI provides a clear excellent endoscopic view of the atrophic border and the demarcation line under various conditions of gastritis. We could recognize gastritis as the lesions of the diffuse redness to purple color area with LCI. On the other hand, EGCs are recognized as the lesions of the orange-red, orange, or orange-white color area in the lesion of the purple color area, which is the surround atrophic mucosa with LCI. With further prospective randomized studies, we will be able to evaluate the diagnosis ability for EGC by IEE, and it will be necessary to evaluate the role of WLI/IEE and the additional effects of the diagnostic ability by adding IEE to WLI in future.

Helicobacter pylori Chronic Infection Selects for Effective Colonizers of Metaplastic Glands.

Chronic gastric infection with Helicobacter pylori can lead to progressive tissue changes that culminate in cancer, but how H. pylori adapts to the changing tissue environment during disease development is not fully understood. In a transgenic mouse gastric metaplasia model, we found that strains from unrelated individuals differed in their ability to infect the stomach, to colonize metaplastic glands, and to alter the expression of the metaplasia-associated protein TFF3. H. pylori isolates from different stages of disease from a single individual had differential ability to colonize healthy and metaplastic gastric glands. Exposure to the metaplastic environment selected for high gastric colonization by one of these strains. Complete genome sequencing revealed a unique alteration in the frequency of a variant allele of the putative adhesin sabB, arising from a recombination event with the related sialic acid binding adhesin (SabA) gene. Mutation of sabB in multiple H. pylori strain backgrounds strongly reduced adherence to both normal and metaplastic gastric tissue, and highly attenuated stomach colonization in mice. Thus, the changing gastric environment during disease development promotes bacterial adhesin gene variation associated with enhanced gastric colonization. IMPORTANCE Chronic infection with Helicobacter pylori is the primary risk factor for developing stomach cancer. As disease progresses H. pylori must adapt to a changing host tissue environment that includes induction of new cell fates in the cells that line the stomach. We tested representative H. pylori isolates collected from the same patient during early and later stages of disease in a mouse model where we can rapidly induce disease-associated tissue changes. Only the later-stage H. pylori strains could robustly colonize the diseased stomach environment. We also found that the ability to colonize the diseased stomach was associated with genetic variation in a putative cell surface adhesin gene called sabB. Additional experiments revealed that SabB promotes binding to stomach tissue and is critical for stomach colonization by the late-stage strains. Thus, H. pylori diversifies its genome during disease progression and these genomic changes highlight critical factors for bacterial persistence.