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Background: Gastric intestinal metaplasia is a common pathological feature in patients with Helicobacter pylori (H. pylori) infection. Rabeprazole was widely used as the first-line regimen for H. pylori infectious treatment. The objective of this study is to explore the mechanism of rabeprazole in gastric intestinal metaplasia treatment. Methods: Real-time PCR, Western blotting (WB) and ROS analysis were conducted to confirm that rabeprazole could induce ferroptosis to suppress gastric intestinal metaplasia. Cellular fraction, luciferase and chromatin immunoprecipitation (ChIP) were used to identify the mechanism underlying rabeprazole modulated ferroptosis. Results: Herein, we found rabeprazole treatment led to inhibit CDX2 and MUC2 expression, alleviating gastric intestinal metaplasia, which was attributed to enhanced ferroptosis characterized by decreased GPX4 expression. Inhibition of ferroptosis by ferrostatin-1 (Fer-1) could reverse decreased CDX2 and MUC2 expression caused by rabeprazole. Mechanically, Rabeprazole could inhibit CREB phosphorylation and nuclear translocation, which further decreased the binding of CREB to GPX4 promoter, reducing GPX4 transactivity. Moreover, endogenous PKA interacted with CREB, and this interaction was drastically destroyed in response to rabeprazole treatment. Most importantly, enhanced ferroptosis was observed in H. pylori- infected gastric intestinal metaplasia in comparison to HC control. Conclusion: These findings suggested that rabeprazole induced ferroptosis to reduce CDX2 expression in gastric epithelial cells through PKA/CREB cascade signaling, implying that targeting ferroptosis could be a promising strategy in improving gastric intestinal metaplasia during H. pylori -infected patients. [ABSTRACT FROM AUTHOR]

Background: Gastric intestinal metaplasia(GIM) is an independent risk factor for GC, however, its pathogenesis is still unclear. Ferroptosis is a new type of programmed cell death, which may be involved in the process of GIM. The purpose of this study was to analyze the expression of ferroptosis-related genes (FRGs) in GIM tissues and to explore the relationship between ferroptosis and GIM. Method: The results of GIM tissue full transcriptome sequencing were downloaded from Gene Expression Omnibus(GEO) database. R software (V4.2.0) and R packages were used for screening and enrichment analysis of differentially expressed genes(DEGs). The key genes were screened by least absolute shrinkage and selection operator(LASSO) and support vector machine-recursive feature elimination(SVM-RFE) algorithm. Receiver operating characteristic(ROC) curve was used to evaluate the diagnostic efficacy of key genes in GIM. Clinical samples were used to further validate hub genes. Results: A total of 12 differentially expressed ferroptosis-related genes (DEFRGs) were identified. Using two machine learning algorithms, GOT1, ALDH3A2, ACSF2 and SESN2 were identified as key genes. The area under ROC curve (AUC) of GOT1, ALDH3A2, ACSF2 and SESN2 in the training set were 0.906, 0.955, 0.899 and 0.962 respectively, and the AUC in the verification set were 0.776, 0.676, 0.773 and 0.880, respectively. Clinical samples verified the differential expression of GOT1, ACSF2, and SESN2 in GIM. Conclusion: We found that there was a significant correlation between ferroptosis and GIM. GOT1, ACSF2 and SESN2 can be used as diagnostic markers to effectively identify GIM. [ABSTRACT FROM AUTHOR]

Background and Aim: Gastric cancer is a health concern and contributes to cancer‐related deaths. Gastric intestinal metaplasia (GIM) is a premalignant lesion of gastric cancer. Currently, factors associated with GIM regression are under‐investigated. This study aims to assess the rate of GIM regression and identify factors associated with it. Methods: This study was conducted at Medstar Washington Hospital Center. We included patients who had GIM between January 2015 and December 2020. Population was divided into GIM persistence or regression. Data included demographics, esophagogastroduodenoscopy findings, Helicobacter pylori status, and laboratory results. Statistical analyses included Kaplan–Meier and Cox proportional models to explore predictors of GIM regression. Results: Among 2375 patients, 9.1% had GIM. Notably, 85 patients had GIM regression and 132 patients had persistent GIM. African Americans constituted (75%) of the regression group and (76%) of the persistence group. Peptic ulcer disease (PUD) was noted in 12.9% of the regression group at baseline, and 5.9% at follow‐up; the persistence group showed 11.4% at baseline and 5.3% at follow‐up (P = 0.89). Regression analysis revealed that the presence of PUD was associated with a higher rate of regression (hazard ratio [HR] 2.46, P = 0.013). Smoking status showed lower rates of regression (HR 0.54 and 0.62, P = 0.038 and 0.169). On gastric mapping, African Americans, Hispanics, and individuals of other races/ethnicities displayed lower rates of GIM regression (HR 0.68, 0.78 and 0.69). Conclusion: PUD was associated with a higher rate of GIM regression, while smoking showed lower regression rates. Results provide insights into factors influencing GIM regression in African American population and may inform future surveillance and treatment strategies. [ABSTRACT FROM AUTHOR]

Chronic infection of Helicobacter pylori is considered the principal cause of gastric cancers, but evidence has accumulated regarding the impact of tobacco smoking and alcohol consumption on the development of gastric cancers. Several possible mechanisms, including the activation of nicotinic acetylcholine receptors, have been proposed for smoking-induced gastric carcinogenesis. On the other hand, local acetaldehyde exposure and ethanol-induced mucosal inflammation have been proposed as the mechanisms involved in the development of gastric cancers in heavy alcohol drinkers. In addition, genetic polymorphisms are also considered to play a pivotal role in smoking-related and alcohol-related gastric carcinogenesis. In this review, we will discuss the molecular mechanisms involved in the development of gastric cancers in relation to tobacco smoking and alcohol consumption. [ABSTRACT FROM AUTHOR]

Gastric cancer (GC) is a significant healthcare concern, and the identification of high-risk patients is crucial. Indeed, gastric precancerous conditions present significant diagnostic challenges, particularly early intestinal metaplasia (IM) detection. This study developed a deep learning system to assist in IM detection using image patches from gastric corpus examined using virtual chromoendoscopy in a Western country. Utilizing a retrospective dataset of endoscopic images from Sant'Andrea University Hospital of Rome, collected between January 2020 and December 2023, the system extracted 200 × 200 pixel patches, classifying them with a voting scheme. The specificity and sensitivity on the patch test set were 76% and 72%, respectively. The optimization of a learnable voting scheme on a validation set achieved a specificity of 70% and sensitivity of 100% for entire images. Despite data limitations and the absence of pre-trained models, the system shows promising results for preliminary screening in gastric precancerous condition diagnostics, providing an explainable and robust Artificial Intelligence approach. [ABSTRACT FROM AUTHOR]

Recognition of gastric conditions during endoscopy exams, including gastric cancer, usually requires specialized training and a long learning curve. Besides that, the interobserver variability is frequently high due to the different morphological characteristics of the lesions and grades of mucosal inflammation. In this sense, artificial intelligence tools based on deep learning models have been developed to support physicians to detect, classify, and predict gastric lesions more efficiently. Even though a growing number of studies exists in the literature, there are multiple challenges to bring a model to practice in this field, such as the need for more robust validation studies and regulatory hurdles. Therefore, the aim of this review is to provide a comprehensive assessment of the current use of artificial intelligence applied to endoscopic imaging to evaluate gastric precancerous and cancerous lesions and the barriers to widespread implementation of this technology in clinical routine. [ABSTRACT FROM AUTHOR]

BackgroundGastric intestinal metaplasia is a common pathological feature in patients with Helicobacter pylori (H. pylori) infection. Rabeprazole was widely used as the first-line regimen for H. pylori infectious treatment. The objective of this study is to explore the mechanism of rabeprazole in gastric intestinal metaplasia treatment.MethodsReal-time PCR, Western blotting (WB) and ROS analysis were conducted to confirm that rabeprazole could induce ferroptosis to suppress gastric intestinal metaplasia. Cellular fraction, luciferase and chromatin immunoprecipitation (ChIP) were used to identify the mechanism underlying rabeprazole modulated ferroptosis.ResultsHerein, we found rabeprazole treatment led to inhibit CDX2 and MUC2 expression, alleviating gastric intestinal metaplasia, which was attributed to enhanced ferroptosis characterized by decreased GPX4 expression. Inhibition of ferroptosis by ferrostatin-1 (Fer-1) could reverse decreased CDX2 and MUC2 expression caused by rabeprazole. Mechanically, Rabeprazole could inhibit CREB phosphorylation and nuclear translocation, which further decreased the binding of CREB to GPX4 promoter, reducing GPX4 transactivity. Moreover, endogenous PKA interacted with CREB, and this interaction was drastically destroyed in response to rabeprazole treatment. Most importantly, enhanced ferroptosis was observed in H. pylori-infected gastric intestinal metaplasia in comparison to HC control.ConclusionThese findings suggested that rabeprazole induced ferroptosis to reduce CDX2 expression in gastric epithelial cells through PKA/CREB cascade signaling, implying that targeting ferroptosis could be a promising strategy in improving gastric intestinal metaplasia during H. pylori-infected patients.

Abstract Background Gastric intestinal metaplasia (GIM) is an essential precancerous lesion. Although the reversal of GIM is challenging, it potentially brings a state-to-art strategy for gastric cancer therapeutics (GC). The lack of the appropriate in vitro model limits studies of GIM pathogenesis, which is the issue this work aims to address for further studies. Method The air-liquid interface (ALI) model was adopted for the long-term culture of GIM cells in the present work. This study conducted Immunofluorescence (IF), quantitative real-time polymerase chain reaction (qRT-PCR), transcriptomic sequencing, and mucoproteomic sequencing (MS) techniques to identify the pathways for differential expressed genes (DEGs) enrichment among different groups, furthermore, to verify novel biomarkers of GIM cells. Result Our study suggests that GIM-ALI model is analog to the innate GIM cells, which thus can be used for mucus collection and drug screening. We found genes MUC17, CDA, TRIM15, TBX3, FLVCR2, ONECUT2, ACY3, NMUR2, and MAL2 were highly expressed in GIM cells, while GLDN, SLC5A5, MAL, and MALAT1 showed down-regulated, which can be used as potential biomarkers for GIM cells. In parallel, these genes that highly expressed in GIM samples were mainly involved in cancer-related pathways, such as the MAPK signal pathway and oxidative phosphorylation signal pathway. Conclusion The ALI model is validated for the first time for the in vitro study of GIM. GIM-ALI model is a novel in vitro model that can mimic the tissue micro-environment in GIM patients and further provide an avenue for studying the characteristics of GIM mucus. Our study identified new markers of GIM as well as pathways associated with GIM, which provides outstanding insight for exploring GIM pathogenesis and potentially other related conditions.

Simple Summary: Individuals with atrophic gastritis and gastric intestinal metaplasia, considered gastric precancerous conditions (GPC), are at increased risk of developing gastric adenocarcinoma. The identification and surveillance of these patients are important for the diagnosis of early gastric neoplasia. Non-invasive markers of GPC with good diagnostic performance could allow the implementation of a stepwise screening approach and, with successful personalized endoscopic surveillance, possibly decrease gastric cancer morbidity and mortality. Pepsinogen I and II and their ratio are the most broadly investigated biomarkers with moderate diagnostic performance. Their combination with other markers like Helicobacter pylori antibodies and gastrin-17 (called GastroPanel®) allows for more precise identification of GPC but without significant improvement in overall performance. Other new serum biomarkers could possibly enhance the performance of pepsinogens. Some of them may be considered stand-alone biomarkers; however, until now, no high-quality data support the use of any of them. Gastric cancer (GC) is still one of the most prevalent cancers worldwide, with a high mortality rate, despite improvements in diagnostic and therapeutic strategies. To diminish the GC burden, a modification of the current diagnostic paradigm, and especially endoscopic diagnosis of symptomatic individuals, is necessary. In this review article, we present a broad review and the current knowledge status on serum biomarkers, including pepsinogens, gastrin, Gastropanel®, autoantibodies, and novel biomarkers, allowing us to estimate the risk of gastric precancerous conditions (GPC)—atrophic gastritis and gastric intestinal metaplasia. The aim of the article is to emphasize the role of non-invasive testing in GC prevention. This comprehensive review describes the pathophysiological background of investigated biomarkers, their status and performance based on available data, as well as their clinical applicability. We point out future perspectives of non-invasive testing and possible new biomarkers opportunities. [ABSTRACT FROM AUTHOR]

Background and Aim: Atrophic gastritis (AG) and gastric intestinal metaplasia (GIM) are early changes in the stepwise progression to gastric adenocarcinoma. There is heterogeneity in international guidelines regarding the endoscopic diagnosis and surveillance of AG and GIM. This study aims to determine the prevalence of GIM in an Australian center and assess the approach of Australian endoscopists for these two conditions. Methods: We conducted a single‐center retrospective study of adult patients between January 2015 and December 2020 diagnosed with GIM on gastric biopsy following upper gastric endoscopy. A web‐based, 25‐question, investigator‐designed, multiple‐choice survey was distributed among all registered endoscopists in Australia. Results: The overall prevalence of GIM within a single Australian center was 11.7% over 5 years. Of the 1026 patients identified, only 58.7% underwent mapping biopsies using the modified Sydney protocol. Among the cohort, 1.6% had low‐grade dysplasia, 0.9% had high‐grade dysplasia, and 1.8% had malignancy on initial gastroscopy. Two hundred and sixty‐seven (7.2%) endoscopists completed the survey, 44.2% indicated they would perform mapping for all patients, and 36% only for high‐risk patients. Only 1.5% (n = 4) of respondents were able to correctly identify all six endoscopic photos of GIM/AG. Conclusion: This study demonstrates that in a large tertiary center, GIM is a prevalent endoscopic finding, but the associated rates of dysplasia and cancer were low. Additionally, among a small proportion of surveyed Australian endoscopists, there is notable variability in the endoscopic approach for AG and GIM and significant knowledge gaps. More training is required to increase the recognition of GIM and compliance with histological mapping. [ABSTRACT FROM AUTHOR]

Background: Gastric intestinal metaplasia (GIM) is an essential precancerous lesion. Although the reversal of GIM is challenging, it potentially brings a state-to-art strategy for gastric cancer therapeutics (GC). The lack of the appropriate in vitro model limits studies of GIM pathogenesis, which is the issue this work aims to address for further studies. Method: The air-liquid interface (ALI) model was adopted for the long-term culture of GIM cells in the present work. This study conducted Immunofluorescence (IF), quantitative real-time polymerase chain reaction (qRT-PCR), transcriptomic sequencing, and mucoproteomic sequencing (MS) techniques to identify the pathways for differential expressed genes (DEGs) enrichment among different groups, furthermore, to verify novel biomarkers of GIM cells. Result: Our study suggests that GIM-ALI model is analog to the innate GIM cells, which thus can be used for mucus collection and drug screening. We found genes MUC17, CDA, TRIM15, TBX3, FLVCR2, ONECUT2, ACY3, NMUR2, and MAL2 were highly expressed in GIM cells, while GLDN, SLC5A5, MAL, and MALAT1 showed down-regulated, which can be used as potential biomarkers for GIM cells. In parallel, these genes that highly expressed in GIM samples were mainly involved in cancer-related pathways, such as the MAPK signal pathway and oxidative phosphorylation signal pathway. Conclusion: The ALI model is validated for the first time for the in vitro study of GIM. GIM-ALI model is a novel in vitro model that can mimic the tissue micro-environment in GIM patients and further provide an avenue for studying the characteristics of GIM mucus. Our study identified new markers of GIM as well as pathways associated with GIM, which provides outstanding insight for exploring GIM pathogenesis and potentially other related conditions. [ABSTRACT FROM AUTHOR]

Abstract Background and Aim Gastric cancer is a health concern and contributes to cancer‐related deaths. Gastric intestinal metaplasia (GIM) is a premalignant lesion of gastric cancer. Currently, factors associated with GIM regression are under‐investigated. This study aims to assess the rate of GIM regression and identify factors associated with it. Methods This study was conducted at Medstar Washington Hospital Center. We included patients who had GIM between January 2015 and December 2020. Population was divided into GIM persistence or regression. Data included demographics, esophagogastroduodenoscopy findings, Helicobacter pylori status, and laboratory results. Statistical analyses included Kaplan–Meier and Cox proportional models to explore predictors of GIM regression. Results Among 2375 patients, 9.1% had GIM. Notably, 85 patients had GIM regression and 132 patients had persistent GIM. African Americans constituted (75%) of the regression group and (76%) of the persistence group. Peptic ulcer disease (PUD) was noted in 12.9% of the regression group at baseline, and 5.9% at follow‐up; the persistence group showed 11.4% at baseline and 5.3% at follow‐up (P = 0.89). Regression analysis revealed that the presence of PUD was associated with a higher rate of regression (hazard ratio [HR] 2.46, P = 0.013). Smoking status showed lower rates of regression (HR 0.54 and 0.62, P = 0.038 and 0.169). On gastric mapping, African Americans, Hispanics, and individuals of other races/ethnicities displayed lower rates of GIM regression (HR 0.68, 0.78 and 0.69). Conclusion PUD was associated with a higher rate of GIM regression, while smoking showed lower regression rates. Results provide insights into factors influencing GIM regression in African American population and may inform future surveillance and treatment strategies.

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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). 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). 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). 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. [Display omitted] [ABSTRACT FROM AUTHOR]

Abstract Background and Aim Atrophic gastritis (AG) and gastric intestinal metaplasia (GIM) are early changes in the stepwise progression to gastric adenocarcinoma. There is heterogeneity in international guidelines regarding the endoscopic diagnosis and surveillance of AG and GIM. This study aims to determine the prevalence of GIM in an Australian center and assess the approach of Australian endoscopists for these two conditions. Methods We conducted a single‐center retrospective study of adult patients between January 2015 and December 2020 diagnosed with GIM on gastric biopsy following upper gastric endoscopy. A web‐based, 25‐question, investigator‐designed, multiple‐choice survey was distributed among all registered endoscopists in Australia. Results The overall prevalence of GIM within a single Australian center was 11.7% over 5 years. Of the 1026 patients identified, only 58.7% underwent mapping biopsies using the modified Sydney protocol. Among the cohort, 1.6% had low‐grade dysplasia, 0.9% had high‐grade dysplasia, and 1.8% had malignancy on initial gastroscopy. Two hundred and sixty‐seven (7.2%) endoscopists completed the survey, 44.2% indicated they would perform mapping for all patients, and 36% only for high‐risk patients. Only 1.5% (n = 4) of respondents were able to correctly identify all six endoscopic photos of GIM/AG. Conclusion This study demonstrates that in a large tertiary center, GIM is a prevalent endoscopic finding, but the associated rates of dysplasia and cancer were low. Additionally, among a small proportion of surveyed Australian endoscopists, there is notable variability in the endoscopic approach for AG and GIM and significant knowledge gaps. More training is required to increase the recognition of GIM and compliance with histological mapping.

Incidence rates of oesophageal adenocarcinoma (OAC) and proximal gastric adenocarcinoma (PGA) have risen in tandem in recent decades. Patients are often diagnosed at advanced stages, resulting in poor prognoses despite aggressive treatment. Cancer screening programs aim to detect early-stage cancer or precancerous conditions, such as dysplasia, in asymptomatic individuals to improve patient outcomes and reduce mortality rates. Precursor lesions can potentially transform into malignancy; however, accurate diagnosis is challenging. This article examines the causes, clinical symptoms, pathological characteristics, and diagnostic complexities of precursor lesions for adenocarcinoma in the oesophagus and stomach. [ABSTRACT FROM AUTHOR]

Abstract 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

Gastric cancer (GC) is a significant healthcare concern, and the identification of high-risk patients is crucial. Indeed, gastric precancerous conditions present significant diagnostic challenges, particularly early intestinal metaplasia (IM) detection. This study developed a deep learning system to assist in IM detection using image patches from gastric corpus examined using virtual chromoendoscopy in a Western country. Utilizing a retrospective dataset of endoscopic images from Sant’Andrea University Hospital of Rome, collected between January 2020 and December 2023, the system extracted 200 × 200 pixel patches, classifying them with a voting scheme. The specificity and sensitivity on the patch test set were 76% and 72%, respectively. The optimization of a learnable voting scheme on a validation set achieved a specificity of 70% and sensitivity of 100% for entire images. Despite data limitations and the absence of pre-trained models, the system shows promising results for preliminary screening in gastric precancerous condition diagnostics, providing an explainable and robust Artificial Intelligence approach.

Summary: 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

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. 2STnY-xvxhAA5nGkWu7hrz Video Abstract [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Screening for gastric cancer is not recommended despite rising rates in certain U.S. populations. We determined possible missed opportunities for the detection and surveillance of preneoplastic lesions among gastric cancer patients in a VA hospital. Methods: This retrospective cohort study included consecutive, newly diagnosed non-cardia gastric adenocarcinoma patients from 11/2007 to 10/2018 at the Houston VA Hospital. We identified missed opportunities for screening based on risk factors (non-White race, smoking, alcohol, Helicobacter pylori infection, gastric ulcers, family history of gastric cancer). We additionally determined missed opportunities for surveillance of known high-risk lesions. Associations between receipt of prior endoscopy for screening or surveillance and cancer-related outcomes (stage, treatment, survival) were determined using logistic regression models. Results: Among 91 gastric cancer patients, 95.6% were men, 51.6% were black, 12.1% were Hispanic, with mean age of 68.0 years (standard deviation 10.8 years). The most common risk factors included non-white race (68.1%), smoking (76.9%), alcohol use (59.3%) and prior H. pylori (12.1%). Most patients had ≥ 1 risk factor for gastric cancer (92.6%), and 76.9% had ≥ 2 risk factors. Only 25 patients (27.5%) had undergone endoscopy prior to cancer diagnosis. Of 14 with known high-risk lesions (i.e., gastric intestinal metaplasia, dysplasia, ulcer), only 2 (14.3%) underwent surveillance endoscopy. Receipt of prior endoscopy was not associated with differences in cancer outcomes. Conclusions: Most patients with newly diagnosed gastric cancer had ≥ 2 known risk factors for gastric cancer but never received prior screening endoscopy. Among the few with known prior preneoplastic lesions, endoscopic surveillance was not consistently performed. [ABSTRACT FROM AUTHOR]

This study discusses whether olfactomedin 4 (OLFM4) could be used as a sensitive and specific biomarker in the early diagnosis of gastric cancer (GC) after gastric intestinal metaplasia (GIM). An integrative analysis combining data derived from the Gene Expression Omnibus (GEO) and cBioPortal databases was performed to investigate the potential molecular biomarker. Immunohistochemistry and quantitative real-time polymerase chain reactions were used to measure the expression of messenger ribonucleic acid (mRNA) and protein by OLFM4. In combination with the gastroscopic findings and the OLFM4 expression in GIM-GC, a predictive model was established. The receiver operator characteristic curve (ROC) was applied to assess the diagnostic value of the model for GIM-GC. According to the GEO and cBioPortal databases, OLFM4 was identified as a key gene in the diagnosis of GIM-GC. Higher protein expression of OLFM4 was found in GIM and GIM-GC compared with chronic superficial gastritis (GS) (p < 0.05). The positive expression rate of OLFM4 in paracancerous tissue (GCP) was higher than in GIM (p > 0.05). There was no significant difference between GIM-GC and GCP (p > 0.05). The mRNA expression of OLFM4 was similar to the protein expression, and the positive expression rate was higher in early GIM-GC than in GIM (p < 0.05). Olfactomedin 4 could be used as a biomarker for the early diagnosis of GIM-GC, and the logistic predictive model could be an effective tool for increasing the early diagnostic rate. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background and Aim: Patients with incomplete gastric intestinal metaplasia (GIM) have a higher risk of gastric cancer (GC) than those with complete GIM. We aimed to clarify whether micromucosal patterns of GIM in magnifying endoscopy with narrow‐band imaging (M‐NBI) were useful for diagnosis of incomplete GIM. Methods: We enrolled patients with a history of endoscopic resection of GC or detailed inspection for suspicious or definite GC. The antrum greater curvature and corpus lesser curvature were regions of interest. Areas with endoscopic findings of light blue crest and/or white opaque substance (WOS) were defined as endoscopic GIM, and subsequent M‐NBI was applied. Micromucosal patterns were classified into Foveola and Groove types, and targeted biopsies were performed on GIM with each pattern. GIM was classified into complete and incomplete types using mucin (MUC)2, MUC5AC, MUC6, and CD10 immunohistochemical staining. The primary endpoint was the association between micromucosal pattern and histological subtype. The secondary endpoint was endoscopic findings associated with incomplete GIM. Results: We analyzed 98 patients with 156 GIMs. Univariate analysis (odds ratio [OR] 3.4, P = 0.004), but not multivariate analysis (OR 0.87, P = 0.822), demonstrated a significant association between micromucosal pattern and subtype. The antrum (OR 3.7, P = 0.006) and WOS (OR 43, P = 0.002) were independent predictors for incomplete GIM. The WOS had 69% sensitivity and 93% specificity. Conclusions: The M‐NBI micromucosal pattern is not useful for diagnosis of GIM subtype. WOS is a promising endoscopic indicator for diagnosis of incomplete GIM. (UMIN‐CTR000041119). [ABSTRACT FROM AUTHOR]

It is unclear whether obesity confers increased risk of non-cardia gastric adenocarcinoma and its precursor, gastric intestinal metaplasia. Here, we examined whether various dimensions of adiposity independently predispose to the development of non-cardia gastric intestinal metaplasia. We compared data from 409 non-cardia gastric intestinal metaplasia cases and 1748 controls without any gastric intestinal metaplasia from a cross-sectional study at the VA Medical Center in Houston, Texas. Participants completed standardized questionnaires, underwent anthropometric measurements, and underwent a study endoscopy with gastric mapping biopsies. Non-cardia gastric intestinal metaplasia cases included participants with intestinal metaplasia on any non-cardia gastric biopsy. We calculated odds ratios (ORs) and 95% confidence intervals (95% CIs) using logistic regression models. Increasing body mass index (BMI) was not associated with risk of non-cardia gastric intestinal metaplasia (per unit BMI adjusted OR, 0.98; 95% CI, 0.96–1.00). Similarly, we found no associations with increase in waist circumference (per 10-cm increase adjusted OR, 0.94; 95% CI, 0.87–1.03) and waist-to-hip ratio (WHR) (per unit WHR adjusted OR, 2.34; 95% CI, 0.37–14.7). However, there was a significant inverse association with gastric intestinal metaplasia and increasing hip circumference, reflecting gluteofemoral obesity (per 10-cm increase adjusted OR, 0.89; 95% CI, 0.80–0.98). The inverse association was observed for both extensive and focal gastric intestinal metaplasia. The independent dimensions of adiposity (BMI, waist circumference) are not associated with increased risk of non-cardia gastric intestinal metaplasia. The inverse association between gluteofemoral obesity and risk of gastric intestinal metaplasia warrants additional study. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background/Aims Previous artificial intelligence (AI) models attempting to segment gastric intestinal metaplasia (GIM) areas have failed to be deployed in real-time endoscopy due to their slow inference speeds. Here, we propose a new GIM segmentation AI model with inference speeds faster than 25 frames per second that maintains a high level of accuracy. Methods Investigators from Chulalongkorn University obtained 802 histological-proven GIM images for AI model training. Four strategies were proposed to improve the model accuracy. First, transfer learning was employed to the public colon datasets. Second, an image preprocessing technique contrast-limited adaptive histogram equalization was employed to produce clearer GIM areas. Third, data augmentation was applied for a more robust model. Lastly, the bilateral segmentation network model was applied to segment GIM areas in real time. The results were analyzed using different validity values. Results From the internal test, our AI model achieved an inference speed of 31.53 frames per second. GIM detection showed sensitivity, specificity, positive predictive, negative predictive, accuracy, and mean intersection over union in GIM segmentation values of 93%, 80%, 82%, 92%, 87%, and 57%, respectively. Conclusions The bilateral segmentation network combined with transfer learning, contrast-limited adaptive histogram equalization, and data augmentation can provide high sensitivity and good accuracy for GIM detection and segmentation.

• GIM rats exhibited gastro-thyroid comorbidities with cold-intolerant. HQJZ treatment restored low-temperature-tropism behavior, enriching fecal butyrate-producing bacteria, and improved thyroid tissue lesions. • In vivo and in vitro experiments proved that butyrate improved thyroid tissue lesions, enhanced the expression of the thyroid TG, TPO, and TSHR genes, promoted T3 and T4 synthesis and secretion. • The gut microbiota-thyroid axis plays a key role in HQJZ improving the low-energy metabolism of GIM rats, which provides solid evidences for the clinical application of HQJZ in cold-intolerant PLGC patients. Gastric intestinal metaplasia (GIM) is a crucial stage in the progression of gastric cancer. Huangqi Jianzhong decoction (HQJZ) has emerged as a leading therapeutic strategy for treating GIM patients with cold intolerance in traditional Chinese medicine clinics, but the detailed mechanism remains poorly understood. The present study aimed to elucidate the molecular mechanism by which HQJZ alleviates GIM in a rat model on the basis of the gut microbiota‒thyroid axis. A GIM rat model was established by administering cold salicylic acid and sodium deoxycholate (SDC) for 12 weeks, followed by gavage treatment with HQJZ for an additional four weeks. Lianpu Yin (LPY) was used as a comparison formula. The cold tolerance characteristics of GIM rats were evaluated using cold tolerance and temperature‒tropism experiment experiments. Thyroid pathological changes were evaluated with HE staining, and thyroid function was measured via quantification of T3 and T4 levels with ELISA. The gut microbiota was analyzed using 16S rRNA gene sequencing, and fecal butyric acid and serum metabolites were quantified utilizing metabolomics. The key molecular mechanism was verified in the Nthy-ori 3–1 cell model. HQJZ, but not LPY, significantly improved gastric mucosa and thyroid tissue lesions in GIM rats, increased the serum levels of the thyroid hormones T3 and T4, and enhanced cold tolerance. HQJZ treatment promoted the enrichment of fecal butyrate-producing bacteria, specifically the bacteria Allobaculum and Bifidobacterium , resulting in a marked increase in fecal butyric acid concentrations. HQJZ treatment significantly diminished the levels of mitochondrial damage-related serum metabolites, including p-cresol sulfate and indoxyl sulfate. Mechanistically, in vivo investigations further demonstrated that butyric acid not only improved thyroid tissue lesions but also restored the fecal microbiota structure, as well as low-temperature tropism, in GIM rats. Furthermore, butyrate diminished the mitochondrial damage induced by SDC in these cells, as evidenced by decreased reactive oxygen species levels and increased ATP production and mitochondrial membrane potential. Importantly, in vitro studies revealed that butyrate protected against SDC-induced injury in Nthy-ori 3–1 cells through the upregulation of TG, TPO, and TSHR expression. HQJZ promotes cold tolerance and improves thyroid function in GIM rats by enriching gut butyrate-producing bacteria. [Display omitted] [ABSTRACT FROM AUTHOR]

ABSTRACT 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.

Several endoscopic findings obtained by magnifying image-enhanced endoscopy (IEE) are reportedly correlated with gastric intestinal metaplasia (IM); however, the differences between magnifying and nonmagnifying IEE for the diagnosis of gastric IM remain unknown. This study included 100 consecutive patients who underwent narrow-band imaging endoscopy. Four areas of the stomach were evaluated using nonmagnifying and magnifying IEE. Light-blue crest (LBC), white opaque substance (WOS), and endoscopic grading of the gastric IM (EGGIM) were assessed. The concordance rates between nonmagnifying and magnifying IEE were 80.5% for LBC and 93.3% for WOS. The strength of agreement between each observation technique showed good reproducibility, with a kappa value of 0.69 and 0.83 for LBC and WOS, respectively. The individual EGGIM score indicated a good correlation between nonmagnifying and magnifying IEE (concordance rate, 75%; kappa value, 0.67). The prevalence of a high EGGIM score in patients with and without gastric cancer (GC) showed a significant difference both with nonmagnifying IEE (odds ratio (OR), 3.3; 95% confidence interval (CI), 1.2–9.0), and magnifying IEE (OR, 3.1; 95% CI, 1.1–8.9). Nonmagnifying IEE has the potential to stratify the individual risk of GC, similar to magnifying IEE, warranting further investigation with histological assessment. [ABSTRACT FROM AUTHOR]

Background: Gastric intestinal metaplasia (IM) is a precancerous stage spanning a morphological spectrum that is poorly represented by human cell line models., Objective: We aim to establish and characterise human IM cell models to better understand IM progression along the cancer spectrum., Design: A large human gastric IM organoid (IMO) cohort (n=28), their clonal derivatives and normal gastric organoids (n=42) for comparison were established. Comprehensive multi-omics profiling and functional characterisation were performed., Results: Single-cell transcriptomes revealed IMO cells spanning a spectrum from hybrid gastric/intestinal to advanced intestinal differentiation. Their lineage trajectories connected different cycling and quiescent stem and progenitors, highlighting differences in gastric to IM transition and the potential origin of IM from STMN1 cycling isthmus stem cells. Hybrid IMOs showed impaired differentiation potential, high lineage plasticity beyond gastric or intestinal fates and reactivation of a fetal gene programme.Cell populations in gastric IM and cancer tissues were highly similar to those derived from IMOs and exhibited a fetal signature. Genomically, IMOs showed elevated mutation burden, frequent chromosome 20 gain and epigenetic deregulation of many intestinal and gastric genes. Functionally, IMOs were FGF10 independent and showed downregulated FGFR2. Several IMOs exhibited a cell-matrix adhesion independent subpopulation that displayed chromosome 20 gain but lacked key cancer driver mutations, potentially representing the earliest neoplastic precursor of IM-induced gastric cancer., Conclusions: Overall, our IMO biobank captured the heterogeneous nature of IM, revealing mechanistic insights on IM pathogenesis and progression, offering an ideal platform for studying early gastric neoplastic transformation and chemoprevention., Competing Interests: Competing interests: SYL and STY have received research sponsorships from Pfizer, Merck, Servier. HC is an inventor on multiple patents related to organoid technology and one patent on a Matrigel replacement. He is also currently head of Roche’s R&D in Basel, as a member of the executive board. His full disclosures can be found on the following website: www.uu.nl/staff/JCClevers/Additional functions. The other authors declare no competing interests., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Intestinal metaplasia (IM) is the inevitable precancerous stage to develop intestinal-type gastric cancer (GC). Deoxycholic acid (DCA) is the main bile acid (BA) component of duodenogastric reflux and has shown an increased concentration during the transition from chronic gastritis to IM associated with continued STAT3 activation. However, the mechanisms underlying how DCA facilitates IM in the gastric epithelium need exploration. We evaluated IM and bile reflux in corpus tissues from 161 subjects undergoing GC screening. Cell survival and proliferation, proinflammatory cytokine expression and TGR5/STAT3/KLF5 axis activity were measured in normal human gastric cells, cancer cells, and organoid lines derived from C57BL/6, FVB/N and insulin-gastrin (INS-GAS) mice treated with DCA. The effects of DCA on IM development were determined in INS-GAS mice with long-term DCA supplementation, after which the gastric bacterial and BA metabolic profiles were measured by 16S rRNA gene sequencing and LC-MS. We revealed a BA-triggered TGR5/STAT3/KLF5 pathway in human gastric IM tissues. In gastric epithelial cells, DCA promoted proliferation and apoptotic resistance, upregulated proinflammatory cytokines and IM markers, and facilitated STAT3 phosphorylation, nuclear accumulation and DNA binding to the KLF5 promoter. DCA triggered STAT3 signaling and the downstream IM marker KLF5 in mouse gastric organoids in vitro and in vivo. In INS-GAS mice, DCA promoted the accumulation of serum total BAs and accelerated the stepwise development of gastric IM and dysplasia. DCA induced gastric environmental alterations involving abnormal BA metabolism and microbial dysbiosis, in which the Gemmobacter and Lactobacillus genera were specifically enriched. Lactobacillus genus enrichment was positively correlated with increased levels of GCA, CA, T-α-MCA, TCA and β-MCA in DCA-administrated INS-GAS mice. DCA promotes nuclear STAT3 phosphorylation, which mediates KLF5 upregulation associated with gastric inflammation and IM development. DCA disturbs the gastric microbiome and BA metabolism homeostasis during IM induction.

Background: Gastric intestinal metaplasia (GIM) is a premalignant gastric mucosal change that is often incidentally detected during esophagogastroduodenoscopy (EGD). Despite the established higher risk of gastric cancer associated with GIM, the incidence, prevalence, and outcomes data for GIM are limited in the United States (US), and practice patterns are highly variable. Objectives: Our primary objectives were to accurately identify incident histology-confirmed GIM cases and determine patient characteristics, endoscopy findings, Helicobacter pylori (HP) detection, and eradication treatment outcomes, as well as surveillance and follow-up recommendations. Design: We conducted a retrospective cohort study using administrative data. Methods: We first developed and validated a rule-based natural language processing tool to identify the patients with GIM on gastrointestinal pathology reports between 2011 and 2016. We then performed a manual chart review of all EGD procedures and associated pathology notes to confirm cases and obtain clinically relevant data. Results: In all, 414 patients with an index diagnosis of GIM were confirmed (prevalence = 2.5% of patients undergoing any EGD). A majority (52.4%) of patients were non-Hispanic white. The most common indication for EGD was abdominal pain (46.9%). A majority (55%) did not receive specific follow-up recommendations or were asked to see their primary care provider. HP testing was documented in 86% of patients, and detected in 94 patients (prevalence = 26.4%). Treatment was documented in 94.7% of cases, and eradication confirmed in only 34.8% of these cases. Conclusion: A large group of US patients with an index diagnosis of GIM was accurately identified. There was wide variability in clinical practice patterns including biopsy practice, HP treatment and eradication confirmation testing, and surveillance recommendations. This work demonstrates that there is a major unmet need for quality improvement efforts to standardize care for patients with GIM, a premalignant condition, and inform future prospective studies in a US population. [ABSTRACT FROM AUTHOR]

Background: Gastric intestinal metaplasia (GIM) is a precursor to gastric adenocarcinoma, making it an attractive target for early detection by endoscopy. The aim of this study was to determine the prevalence, risk factors, and associated histologic findings of GIM among patients undergoing endoscopy in a diverse US population. Methods: We conducted a retrospective, cross-sectional study of patients undergoing elective endoscopy with gastric biopsies at 6 academic and community centers in Houston, Texas. GIM prevalence was estimated with a 95% confidence interval (CI), and patient demographic and clinical characteristics were summarized using mean with standard deviation, or frequency with percentage. Generalized estimating equations (GEE) were used to compare characteristics between those with and without GIM. Results: Our final cohort consisted of 2685 patients, including 216 cases with GIM and 2469 controls. The prevalence of GIM in our cohort was 8.04% (95% CI 7.07%, 9.14%). The mean age of GIM cases was higher than in the control group (59.8 vs 54.7 years, p < 0.0001). The prevalence of GIM in Asians, Hispanic, Black and Non-Hispanic Whites (NHW) was 14.7%, 11.7%, 9.8% and 5.8%, respectively. On multivariable analysis, factors associated with GIM include age (adj. OR 1.32 per 10 year increase, p < 0.0001), habitual smoking (adj. OR 1.68, p < 0.0001), and race (compared to NHW: Asian, adj. OR 2.34, p = 0.010; Hispanic, adj. OR 2.15, p < 0.001; Black, adj. OR 1.61, p < 0.001). Conclusion: Asians, Hispanics, and African Americans have higher rates of GIM than NHW. Ethnicity should be an important consideration on determining who to screen for GIM in the US. [ABSTRACT FROM AUTHOR]

Background/Aims: Screening for gastric intestinal metaplasia (GIM) may lead to early gastric cancer detection. We developed and validated a pre-endoscopy risk prediction model for detection of GIM based on patient-level risk factors in a U.S. population. Methods: We used data from 423 GIM cases and 1796 controls from a cross-sectional study among primary care and endoscopy clinic patients at the Houston VA. We developed the model using backwards stepwise regression and assessed discrimination using area under the receiver operating characteristic (AUROC). The model was internally validated using cross-validation and bootstrapping. The final expanded model was compared to a model including H. pylori infection alone and a baseline model including remaining terms without H. pylori. Results: Male sex, older age, non-white race/ethnicity, smoking status, and H. pylori were associated with GIM risk. The expanded model including these terms had AUROC 0.73 (95%CI 0.71–0.76) for predicting GIM and AUROC 0.82 (95%CI 0.79–0.86) for extensive GIM. This model discriminated better than a model including only H. pylori (AUROC 0.66; 95%CI 0.63–0.68) and the baseline model (AUROC 0.67; 95%CI 0.64–0.70). The expanded model performed similarly among primary care (AUROC 0.75) and endoscopy (AUROC 0.73) patients. The expanded model showed sufficient internal validity (cross-validation AUROC 0.72) with little evidence of over-fitting. Conclusions: We develop and validate a non-invasive risk model for GIM detection in a U.S. population that included terms for sex, age, race/ethnicity, smoking status, and H. pylori infection. Validated risk models would identify individuals with GIM who should be referred for endoscopic screening. [ABSTRACT FROM AUTHOR]

Routine preoperative endoscopic evaluation for bariatric surgery is controversial; however, for patients undergoing endoscopy, some findings may alter surgical management. Gastric intestinal metaplasia (GIM) is found in up to 11.7% of the general population. When associated with determined risk factors, GIM has a risk of progressing to gastric cancer. The aim of our study was to assess the prevalence of GIM and possible associated factors in those undergoing bariatric surgery. We performed a retrospective chart review of patients who underwent primary sleeve gastrectomy or Roux-en-Y gastric bypass at our institution between January 1, 2016 and June 30, 2020. Baseline characteristics and preoperative endoscopic findings were obtained from all patients. Histopathologic analysis of sleeve gastrectomy specimens was reviewed. We identified 753 patients. Mean (SD) age and body mass index were 49.0 (13.1) years and 43.9 (7.1) kg/m2, respectively. Procedures consisted of 411 (54.6%) gastric bypasses and 342 (45.4%) sleeve gastrectomies. Esophagitis and Barrett esophagus were found in 18.1% and 5.0% of patients, respectively. Preoperative gastric biopsy identified Helicobacter pylori in 6.4% and GIM in 2.7%. Regression analysis found an association of Barrett esophagus (odds ratio 4.60; 95% CI 1.25–16.82) and age ≥ 60 years (odds ratio 2.67; 95% CI 1.04–6.90) with preoperative findings of GIM. Histopathologic analysis of sleeve gastrectomy specimens identified H. pylori in 1.8% and GIM in 0.9%. Older age and Barrett esophagus were associated with GIM in preoperative gastric biopsy. This association emphasizes the importance of a diligent examination during preoperative endoscopy. [ABSTRACT FROM AUTHOR]

Objective: To conduct a systematic review and meta-analysis on the prediction of severity of gastric intestinal metaplasia (GIM) in localized and entire gastric mucosa using endoscopy. Methods: The authors searched Web of Science, PubMed, Embase and Cochrane Central Register of Controlled Trials and performed systematic searches on endoscopic grading of GIM of the entire stomach using Meta-DiSc and Stata. Results: Sensitivity and specificity for the stratified prediction of overall GIM were 0.91 (95% CI: 0.85-0.95) and 0.91 (95% CI: 0.88-0.93), respectively. Sensitivity in predicting the different grades of GIM was higher in operative link on GIM assessment grades 0, III and IV but lower in grades I and II. Conclusion: Digital chromoendoscopy is well suited to predicting the severity of localized and overall GIM. [ABSTRACT FROM AUTHOR]

In recent years, deep learning (DL) has successfully been implemented to detect gastric intestinal metaplasia (GIM). However, works rarely achieve real-time diagnosis robust enough to be deployed in a real-world scenario e.g. multiple colour modes (white light endoscopy and narrow-band imaging), different endoscope ranges (close-up and far-off) etc. In this paper, we present a novel real-time segmentation of GIM. A switch adapter module (SAM) and a colour selector (CS) are incorporated to execute specific downstream tasks for each colour mode. Moreover, a high resolution (HR) technique with a half-precision compression is applied to enrich performance and maintain inference speed. By adding normal esophagogastroduodenoscopy (EGD) in different endoscopic ranges, our dataset is more realistic. In terms of precision, our model outperforms all benchmarks. Our results reveal sensitivity, specificity, positive predictive, negative predictive, accuracy, and mean intersection over union (IoU) values of 94%, 97%, 93%, 92%, 98%, and 55%, respectively, for GIM segmentation. Ultimately, with a specificity of 97.89% on close-up images, our model can function at close range. • A real-time semantic segmentation network for gastric intestinal metaplasia (GIM) to prevent gastric cancer. • A modified deep neural network with a switch adapter module that supports multiple colour modes and different endoscope ranges in the GIM segmentation. • The model is enhanced by processing high-resolution images with a better view of the surface pattern. • Experiments reveal full comparisons of real-world scenarios and are validated by experienced endoscopists. [ABSTRACT FROM AUTHOR]

There are reports that nut consumption provides potential benefit for gastric pathologies including stomach cancer and Helicobacter pylori infection. However, there are no studies investigating the effect of nut consumption on gastric intestinal metaplasia (GIM). In a Korean cohort of 53 424 men (average age 38.7 ± 7.0 years) and 33 024 women (average age 38.0 ± 7.0 years), we analysed the risk of GIM according to the frequency of nut consumption (peanuts, pine nuts and almonds only) as the following: rare (<1 serving/month), ≤1 serving/month and <1 serving/week, ≤1 serving/week and <3 serving/week, ≤3 serving/week and <5 serving/week and ≥5 serving/week where one serving is 15 g. Cox proportional hazards model was used to calculate the multivariable‐adjusted hazard ratio (HR) for GIM and their 95% confidence intervals (CI) in each group (adjusted HR [95% CI]). Subgroup analysis was conducted by body mass index (BMI, non‐obesity <25 and obesity ≥25). The models were adjusted for age, regular exercise, BMI, smoking, alcohol intake (g/day), diabetes mellitus, hypertension, dietary fibre intake, sodium intake and total calorie intake. After 5.3 years (median 5.9 years) of follow‐up, GIM was observed in 5073 subjects. In men, compared with rare nuts consumption, greater nuts consumption was associated with a lower risk of GIM (rare consumption: reference, 1/month–1/week: 0.85 [0.79–0.91], 1–3/week: 0.81 [0.72–0.91], 3–5/week: 0.70 [0.57–0.86] and ≥5/week: 0.59 [0.48–0.73]). Subgroup analysis indicated that the inverse relationship between nuts consumption and the risk of GIM is more distinct in men without obesity (rare consumption: reference, 1/month–1/week: 0.83 [0.76–0.91], 1–3/week: 0.78 [0.67–0.91], 3–5/week: 0.68 [0.51–0.89] and ≥5/week: 0.51 [0.37–0.69]). However, this association was not observed in women. In conclusion, increased nuts consumption was associated with a decreased risk of GIM in working aged Korean men. [ABSTRACT FROM AUTHOR]

Intestinal metaplasia of the stomach (IM) is considered a pre-cancerous lesion and is a potential precursor to adenocarcinoma. Metabolic syndrome (MetS) has been associated with lesions to the gastrointestinal tract such as the risk of developing Barett esophagus. Vascular endothelial growth factor and leptin have been associated with either gastrointestinal tract carcinogenesis or MetS. In this context, this study was designed to analyze plasma levels of VEGF and leptin in patients with IM and MetS. Four groups of 137 participants (a control group and three patient groups, IM, MetS and IM- MetS) were created. Inclusion criteria for the presence of IM were endoscopic findings and histological confirmation, while for MetS the ATP III and IDF guidelines. Levels of plasma vascular endothelial growth factor (VEGF) and leptin (Leptin) were determined. VEGF levels were increased in IM (IM vs Control, p=0,011) and IM-MetS groups (IM-MetS vs Control, p <0.001 and IM-MetS vs MetS, p=0.001). Leptin levels were found to be increased in the MetS group (MetS vs. Control, p <0.001 and MetS vs IM, p <0.001) and in IM-MetS (IM-MetS vs Control, p = 0.002, IM-MetS vs IM, p=0.033). Patients with intestinal metaplasia and metabolic syndrome (I M - Me t S g r o u p) have elevated levels of VEGF, while leptin levels were associated predominantly with MetS and not with IM. [ABSTRACT FROM AUTHOR]

Background/Aims: Previous artificial intelligence (AI) models attempting to segment gastric intestinal metaplasia (GIM) areas have failed to be deployed in real-time endoscopy due to their slow inference speeds. Here, we propose a new GIM segmentation AI model with inference speeds faster than 25 frames per second that maintains a high level of accuracy. Methods: Investigators from Chulalongkorn University obtained 802 histological-proven GIM images for AI model training. Four strategies were proposed to improve the model accuracy. First, transfer learning was employed to the public colon datasets. Second, an image preprocessing technique contrast-limited adaptive histogram equalization was employed to produce clearer GIM areas. Third, data augmentation was applied for a more robust model. Lastly, the bilateral segmentation network model was applied to segment GIM areas in real time. The results were analyzed using different validity values. Results: From the internal test, our AI model achieved an inference speed of 31.53 frames per second. GIM detection showed sensitivity, specificity, positive predictive, negative predictive, accuracy, and mean intersection over union in GIM segmentation values of 93%, 80%, 82%, 92%, 87%, and 57%, respectively. Conclusions: The bilateral segmentation network combined with transfer learning, contrast-limited adaptive histogram equalization, and data augmentation can provide high sensitivity and good accuracy for GIM detection and segmentation. [ABSTRACT FROM AUTHOR]

Abstract Background Studies have shown the value of subtypes and distribution of gastric intestinal metaplasia (GIM) for prediction of gastric cancer. We aim to combine GIM subtypes and distribution to form a new scoring system for GIM. Methods This was a cross-sectional study. No GIM, type I, II, and III GIM of gastric antrum and corpus scored 0–3 points respectively. Then the severity of the whole stomach was calculated in two ways: 1. The gastric antrum and corpus scores were added together, with a score ranging from 0 to 6, which named “Subtype Distribution Score of Gastric Intestinal Metaplasia (SDSGIM)”. 2. Direct classification according to a table corresponding to that of OLGIM. We compared the SDSGIM among benign lesions, dysplasia, and cancer and drew receiver operating characteristic (ROC) curve to determine the optimal cut-off value. According to the cut-off value and the classification from the table, the predictive ability of these two methods were calculated. Results 227 patients were included. For SDSGIM, benign lesion group was significantly different from dysplasia or cancer group. Area under curve of ROC curve was 0.889 ± 0.023. The optimal cut-off value was 3. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of SDSGIM for malignancy were 89.5%, 78.0%, 74.6%, 91.2% and 82.8%. And those for the second classification method were 84.2%, 82.6%, 77.7%, 87.9%, and 83.3% respectively. Conclusions This study firstly combined GIM subtypes with its distribution forming a novel scoring system, which showed high prediction accuracy for malignant lesions.

Intestinal metaplasia of the stomach (IM) is considered a pre-cancerous lesion and is a potential precursor to adenocarcinoma. Metabolic syndrome (MetS) has been associated with lesions to the gastrointestinal tract such as the risk of developing Barett esophagus. Vascular endothelial growth factor and leptin have been associated with either gastrointestinal tract carcinogenesis or MetS. In this context, this study was designed to analyze plasma levels of VEGF and leptin in patients with IM and MetS. Four groups of 137 participants (a control group and three patient groups, IM, MetS and IM- MetS) were created. Inclusion criteria for the presence of IM were endoscopic findings and histological confirmation, while for MetS the ATP III and IDF guidelines. Levels of plasma vascular endothelial growth factor (VEGF) and leptin (Leptin) were determined. VEGF levels were increased in IM (IM vs Control, p=0,011) and IM-MetS groups (IM-MetS vs Control, p

Evidence suggests that Helicobacter pylori plays a role in gastric cancer (GC) initiation. However, epidemiologic studies on the specific role of other bacteria in the development of GC are lacking. We conducted a case‐control study of 89 cases with gastric intestinal metaplasia (IM) and 89 matched controls who underwent upper gastrointestinal endoscopy at three sites affiliated with NYU Langone Health. We performed shotgun metagenomic sequencing using oral wash samples from 89 case‐control pairs and antral mucosal brushing samples from 55 case‐control pairs. We examined the associations of relative abundances of bacterial taxa and functional pathways with IM using conditional logistic regression with and without elastic‐net penalty. Compared with controls, oral species Peptostreptococcus stomatis, Johnsonella ignava, Neisseria elongata and Neisseria flavescens were enriched in cases (odds ratios [ORs] = 1.29‐1.50, P =.004‐.01) while Lactobacillus gasseri, Streptococcus mutans, S parasanguinis and S sanguinis were under‐represented (ORs = 0.66‐0.76, P =.006‐.042) in cases. Species J ignava and Filifactor alocis in the gastric microbiota were enriched (ORs = 3.27 and 1.43, P =.005 and.035, respectively), while S mutans, S parasanguinis and S sanguinis were under‐represented (ORs = 0.61‐0.75, P =.024‐.046), in cases compared with controls. The lipopolysaccharide and ubiquinol biosynthesis pathways were more abundant in IM, while the sugar degradation pathways were under‐represented in IM. The findings suggest potential roles of certain oral and gastric microbiota, which are correlated with regulation of pathways associated with inflammation, in the development of gastric precancerous lesions. What's new? There's not much evidence for how gut bacteria, besides H. pylori, contribute to gastric cancer risk. Here, the authors used metagenome sequencing to characterize the differences in bacterial microbiota in gastric precancerous lesion cases compared with healthy controls. In gastric intestinal metaplasias, they found higher proportions of several species related to periodontal disease as well as opportunistic pathogens, but lower levels of certain commensals and probiotic species. Metagenomic analysis revealed pathways that were associated with gastric intestinal metaplasias, suggesting a possible mechanism for how the bacteria influence disease risk. [ABSTRACT FROM AUTHOR]

Background: Independent risk factors for chronic atrophic gastritis, gastric intestinal metaplasia and gastric cancer are: Helicobacter pylori infection (especially virulent CagA strains), genetic factors (advanced age, reflecting the duration of Helicobacter pylori infection, male gender, family history of gastric cancer in first-degree relatives), gastric ulcer, biliary reflux, acute or chronic gastric inflammation, smoking, alcohol consumption, prolonged use of proton pump inhibitors or non-steroidal anti-inflammatory drugs, diet low in fruits, vegetables and vitamin C, excessive salt intake and consumption of canned foods with salt). Helicobacter pylori infection and inflammatory cells induce the expression of inducible nitric oxide synthase in the gastroduodenal mucosa, which causes various clinical lesions (duodenal ulcer, gastric ulcer and chronic gastritis without ulcer). Another important condition associated with Helicobacter pylori infection is gastric cancer. Overproduction of nitric oxide, through inducible nitric oxide synthase and oxidative stress, is a genotoxic and mutagenic metabolism which plays a crucial role in the process of gastric carcinogenesis. Conclusions: Chronic atrophic gastritis is considered a multifaceted condition because it can manifest itself through a variable spectrum of nonspecific gastric and extra-gastric symptoms, with an overlap of the clinical features of the two entities of chronic atrophic gastritis – autoimmune and associated with Helicobacter pylori infection. Thus, in contrast to the classic perception of a silent condition, patients with chronic atrophic gastritis report a wide range of gastrointestinal symptoms, ranging from dyspeptic symptoms to those of gastroesophageal reflux.

Background: Gastric intestinal metaplasia is seen chronic gastritis associated with Helicobacter pylori. The objective of this study was to determine the prevalence of subtypes of intestinal metaplasia and presence of Helicobacter pylori infection. Materials and Methods: This was a cross sectional study done at Kathmandu Medical College teaching Hospital in Pathology department from December 2018 to August 2019. The endoscopic biopsies were evaluated for intestinal metaplasia and Helicobacter pylori with the help of Hematoxylin and Eosin stains as well as Giemsa stain. Subtypes of intestinal metaplasia were classified with the help of periodic acid- Schiff/Alcian Blue stain combination and High Iron Diamine- Alcian Blue stain at pH 2.5. The relationship between Helicobacter pylori and subtypes of intestinal metaplasia were compared. Fisher’s exact test was used for statistical evaluation. A p value of ˂0.05 was considered as statistically significant. Results: The prevalence of intestinal metaplasia was found in 57 (12.2%) biopsies. Type I intestinal metaplasia was found in 23 (40.4%) biopsies, type II in 10 (17.5%) biopsies and type III in 24 (42.1%) biopsies. Helicobacter pylori was positive in 28(49.1%) and it was negative in 29(50.9%) biopsies. No statistical significant correlation was seen in the subtypes of intestinal metaplasia with Helicobacter pylori status (p˃0.05). Conclusion: Intestinal metaplasia is frequently observed in endoscopic biopsies, most common being type III subtype.

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.