Inflammation as a Mediator of Microbiome Dysbiosis-Associated DNA Methylation Changes in Gastric Premalignant Lesions.

Evidence for the influence of chronic inflammation induced by microbial dysbiosis on aberrant DNA methylation supports a plausible connexion between disordered microbiota and precancerous lesions of gastric cancer (PLGC). Here, a comprehensive study including multi-omics data was performed to estimate the relationships amongst the gastric microbiome, inflammatory proteins and DNA methylation alterations and their roles in PLGC development. The results demonstrated that gastric dysbacteriosis increased the risk of PLGC and DNA methylation alterations in related tumour suppressor genes. Seven inflammatory biomarkers were identified for antrum and corpus tissues, respectively, amongst which the expression levels of several biomarkers were significantly correlated with the microbial dysbiosis index (MDI) and methylation status of specific tumour suppressor genes. Notably, mediation analysis revealed that microbial dysbiosis partially contributed to DNA methylation changes in the stomach via the inflammatory cytokines C-C motif chemokine 20 (CCL20) and tumour necrosis factor receptor superfamily member 9 (TNFRSF9). Overall, these results may provide new insights into the mechanisms that might link the gastric microbiome to PLGC. Supplementary Information: The online version contains supplementary material available at 10.1007/s43657-023-00118-w.

Endoscopic diagnosis and treatment in gastric cancer: Current evidence and new perspectives.

Gastric cancer is the fifth most common cause of cancer related deaths worldwide. Despite advancement in endoscopic techniques, the majority of the cases are diagnosed at late stage, when the curative treatment options are very limited. The early gastric cancer (EGC) on the other side is potentially curable, and in selected cases endoscopic resection techniques offer similar survival rates then surgical resection. The detection of EGC is endoscopically challenging and requires high quality examination. Recent data show that close to 10% of the gastric cancer cases had a previous negative endoscopy. This highlights the urgent need to improve the quality of the endoscopy services, what can be achieved by increasing the awareness of gastroenterologists and continuously monitoring the key performance indicators of upper gastrointestinal endoscopy. Newer endoscopic imaging techniques are also becoming commonly available to aid the detection of gastric premalignant lesions and EGC. High-definition endoscopy with image enhancement techniques is preferred over white light endoscopy to recognize these lesions, and they are also useful to determine the invasion depth of EGC. The endoscopic optical characterization of lesions is necessary for the selection of proper resection method and decide whether endoscopic resection techniques can be considered. Artificial intelligence systems aid the detection of EGC and can help to determine the depth of invasion. Endoscopic mucosal resection and endoscopic submucosal dissection requires centralized care and tertiary referral centers with appropriate expertise to ensure proper patient selection, high success rate and low adverse event rate. Appropriately scheduled endoscopic surveillance of high-risk patients, premalignant lesions and after resection of EGC is also important in the early detection and successful treatment of gastric cancer.

Protective effects of all-trans retinoic acid against gastric premalignant lesions by repressing exosomal LncHOXA10-pyruvate carboxylase axis.

PURPOSE: Long noncoding RNAs (LncRNAs) play a pivotal role in gastric tumorigenesis, while exosomes facilitate the LncRNAs transferring to recipient cells. However, the roles of exosomal LncRNAs in gastric premalignant lesions (GPL) remain unclear. METHODS: We analyzed the expression of LncHOXA10 and its role in GPL progression. The protective effect of all-trans retinoic acid (ATRA) on GPL was explored in vitro and in vivo. RESULTS: Here, we found that LncHOXA10 expression was obviously increased in serum exosomes and gastric tissues from individuals with GPL, and exosomal LncHOXA10 from patients with GPL markedly promoted the malignant progression of human gastric epithelial cell line GES-1. Furthermore, RNA-pulldown assay revealed that LncHOXA10 mainly interacted with pyruvate carboxylase (PC), an essential enzyme in various cellular metabolic pathways. In gastric tissues from patients with GPL and gastric cancer (GC), PC was also upregulated and positively correlated with LncHOXA10 expression, which predicted a poor prognosis as well. Moreover, PC silencing attenuated the malignant effects of exosomal LncHOXA10 on GES-1 cells. ATRA also ameliorated the deterioration of GPL and prevented the malignant progression of GPL by reducing exosomal LncHOXA10 and PC expression. CONCLUSIONS: Collectively, the LncHOXA10-PC axis participated in the early stage of GC tumorigenesis, and ATRA might be useful to prevent GPL from developing into GC because it targets this axis.

Implementation of endoscopic submucosal dissection in a country with a low incidence of gastric cancer: Results from a prospective national registry.

INTRODUCTION: Endoscopic submucosal dissection (ESD) has become the treatment of choice for early gastric malignancies. In recent years, the ESD technique has been implemented in Western countries with increasing use. OBJECTIVES: To describe the results of gastric ESD in a Western country with a low incidence of gastric cancer. PATIENTS AND METHODS: The prospective national registry was conducted over 4 years in 23 hospitals, including 30 endoscopists. Epithelial and subepithelial lesions (SEL) qualified to complete removal with ESD were assessed. The technique, instruments, and solution for submucosal injection varied at the endoscopist's discretion. ESD was defined as difficult when: en-bloc resection was not achieved, had to be converted to a hybrid resection, lasted more than 2 h or an intraprocedural perforation occurred. Additionally, independent risk factors for difficult ESD were analyzed. RESULTS: Two hundred and thirty gastric ESD in 225 patients were performed from January 2016 to December 2019 (196 epithelial and 34 SEL). Most lesions were located in the lower stomach (111; 48.3%). One hundred and twenty-eight (55.6%) ESD were considered difficult. The median procedure time was 105 min (interquartile range [IQR]: 60-150). The procedure time for SEL was shorter than for epithelial lesions (90 min [45-121] vs. 110 min [62-160]; p = 0.038). En-bloc, R0, and curative resection rates were 91.3%, 75.2%, and 70.9%, respectively. Difficult ESD had lower R0 resection rates than ESD that did not meet the difficulty criteria (64.8% and 87.6%; p = 0.000, respectively). Fibrosis and poor maneuverability were independent factors associated with difficult ESD (OR 3.6, 95%CI 1.1-11.74 and OR 5.07, 95%CI 1.6-16.08; respectively). CONCLUSIONS: Although the number of cases is limited, the results of this analysis show acceptable en-bloc and R0 rates in gastric ESD considering the wide variability in experience among the operators. Fibrosis and poor maneuverability were associated with more difficulty in completing ESD.

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...