Revealing the pathogenesis of gastric intestinal metaplasia based on the mucosoid air-liquid interface.

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.

The Impact of Tobacco Smoking and Alcohol Consumption on the Development of Gastric Cancers.

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.

Gastric intestinal metaplasia regression in United States population: A retrospective longitudinal study.

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.

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.

Gastric intestinal metaplasia: Prevalence in a large Australian center and nationwide survey of endoscopic practice.

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.

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.

Non-Invasive Markers for the Detection of Gastric Precancerous Conditions.

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.

Artificial intelligence for gastric cancer in endoscopy: From diagnostic reasoning to market.

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.

Convolutional Neural Network Model for Intestinal Metaplasia Recognition in Gastric Corpus Using Endoscopic Image Patches.

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.

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.

Weiwei Decoction alleviates gastric intestinal metaplasia through the olfactomedin 4/nucleotide-binding oligomerization domain 1/caudal-type homeobox gene 2 signaling pathway.

BACKGROUND: Gastric intestinal metaplasia (IM) is a precancerous lesion that is associated with an elevated risk of gastric carcinogenesis. Weiwei Decoction (WWD) is a promising traditional Chinese herbal formula widely employed in clinical for treating IM. Previous studies suggested the potential involvement of the olfactomedin 4 (OLFM4)/nucleotide-binding oligomerization domain 1 (NOD1)/caudal-type homeobox gene 2 (CDX2) signaling pathway in IM regulation. AIM: To verify the regulation of the OLFM4/NOD1/CDX2 pathway in IM, specifically investigating WWD's effectiveness on IM through this pathway. METHODS: Immunohistochemistry for OLFM4, NOD1, and CDX2 was conducted on tissue microarray. GES-1 cells treated with chenodeoxycholic acid were utilized as IM cell models. OLFM4 short hairpin RNA (shRNA), NOD1 shRNA, and OLFM4 pcDNA were transfected to clarify the pathway regulatory relationships. Protein interactions were validated by co-immunoprecipitation. To explore WWD's pharmacological actions, IM rat models were induced using N-methyl-N'-nitro-N-nitrosoguanidine followed by WWD gavage. Gastric cells were treated with WWD-medicated serum. Cytokines and chemokines content were assessed by enzyme-linked immunosorbent assay and quantitative reverse transcription polymerase chain reaction. RESULTS: The OLFM4/NOD1/CDX2 axis was a characteristic of IM. OLFM4 exhibited direct binding and subsequent down-regulation of NOD1, thereby sustaining the activation of CDX2 and promoting the progression of IM. WWD improved gastric mucosal histological lesions while suppressing intestinal markers KLF transcription factor 4, villin 1, and MUCIN 2 expression in IM rats. Regarding pharmacological actions, WWD suppressed OLFM4 and restored NOD1 expression, consequently reducing CDX2 at the mRNA and protein levels in IM rats. Parallel regulatory mechanisms were observed at the protein level in IM cells treated with WWD-medicated serum. Furthermore, WWD-medicated serum treatment strengthened OLFM4 and NOD1 interaction. In case of anti-inflammatory, WWD restrained interleukin (IL)-6, interferon-gamma, IL-17, macrophage chemoattractant protein-1, macrophage inflammatory protein 1 alpha content in IM rat serum. WWD-medicated serum inhibited tumor necrosis factor alpha, IL-6, IL-8 transcriptions in IM cells. CONCLUSION: The OLFM4/NOD1/CDX2 pathway is involved in the regulation of IM. WWD exerts its therapeutic efficacy on IM through the pathway, additionally attenuating the inflammatory response.

Aumento de detección de lesiones gástricas premalignas mediante protocolo Sydney en comparación con biopsias no protocolizadas / Increased detection of premalignant gastric lesions through Sydney protocol in comparison with non-protocolized gastric biopsies

Introduction: Gastric cancer (GC) is the leading cause of cancer mortality in Chile. The development ofgastric adenocarcinoma its preceded by a histopathologic cascade composed of gastric atrophy, intestinal metaplasia and gastric dysplasia. Sydney protocol has been proposed as the standard method for diagnosingthese conditions. The aim of this research study was to establish whether Sydney protocol increase thedetection of premalignant gastric lesions, as gastric atrophy and intestinal metaplasia, compared to non protocolizedendoscopies/biopsies. Methods: Upper gastroduodenal endoscopies (GDE) from Hospital Clí-nico Universidad Católica de Chile between April-May 2015 and April-May 2016 was analyzed. Patientswith histological study with 18 years-old or older were included. Patients with history of GC or malignantlesions at GDE where excluded. Detection of gastric atrophy, intestinal metaplasia and suggestive findingsof autoimmune gastritis where compared between Sydney protocol and non-protocolized endoscopies/biopsies...

Introducción: El cáncer gástrico (CG) es la principal causa de muertes por cáncer en Chile. El desarrollo del adenocarcinoma gástrico es precedido por una cascada histopatológica (gastritis; atrofia gástrica/AG; metaplasia intestinal/MI). Se ha propuesto la biopsia del cuerpo, ángulo y antro a través del protocolo de Sydney para la búsqueda de estas condiciones. Objetivo: Determinar la diferencia en la detección delesiones premalignas gástricas a través del protocolo de Sydney comparado con el estudio endoscópico habitual. Métodos: Se analizaron las endoscopias digestivas altas (EDA) realizadas en el Centro de Endoscopia Digestiva del Hospital Clínico de la Universidad Católica en los períodos entre abril y mayo del 2015 y 2016. Se incluyeron las EDA de pacientes mayores de 18 años con estudio histológico. Fueron excluidos los pacientes con antecedente personal de CG o lesiones de aspecto maligno macroscópicas. Se comparó la detección de AG, MI y gastritis autoinmune (GA) en el estudio histológico entre los pacientes con protocolo Sydney y el estudio endoscópico no protocolizado...