Premalignant Gastric Lesions Research Articles

The role of the S100A8/S100A9 in gastric tumor progression

Gastric premalignant lesions can develop into cancer through multiple steps and inflammation plays a critical role. The aim of this study is to uncover the characteristics of macrophages and their gene expression in premalignant gastric lesions to identify novel biomarkers and potential targets for treatment. We used the computational algorithm CIBERSORT to estimate immune cell subsets present in gastric tissue. We applied WGCNA to identify inflammation-related modules and hub genes. Single-cell analysis was used to identify macrophage sub-clusters specific to pathology. In addition, the in-vitro experiment was performed to verify the mechanism of the key inflammatory factors in the growth of gastric cancer. WGCNA identified a module that was positively correlated with pathological changes and highly related to inflammation scores. Single-cell analysis revealed a macrophage subset, and we observed that S100A8 and S100A9 + macrophages made up a significantly higher proportion in early gastric cancer (EGC) tissues. Our functional enrichment analysis suggested that these macrophages may play a role in gastric tumorigenesis through the activation of the NFκB signaling pathway. In vitro experiments verified that S100A9 can promote the proliferation and migration of AGS cells through the TLR4-NFκB signaling pathway, and the S100A8/S100A9 inhibitor Paquinimod can inhibit their proliferation and migration. Our findings suggest that S100A8 and S100A9 + macrophages may activate the TLR4-NFκB signaling pathway to promote cell proliferation and migration leading to gastric tumor progression. Macrophages with high expression of S100A8/S100A9 are critical in the progression of gastric inflammation to cancer. Cytokine S100A9 can activate the TLR4-NFκB signaling pathway and promote the proliferation and migration of gastric adenocarcinoma cells.

Biopsy-Proven Gastric Pathological Findings in Mechanically Ventilated Intensive Care Unit Patients.

Objectives Helicobacter pylori (H. pylori) is known to affect a large proportion of the world population. It plays a role in the pathogenesis of peptic ulcer (PU) and increases the likelihood of bleeding. In critically ill patients in intensive care units (ICUs), the risk of bleeding may be much higher due to many concomitant factors. The study aimed to determine the activation of H. pylori in mechanically ventilated (MV) intensive care patients and compare this with the general population. Methods This study was performed retrospectively by screening patients who underwent esophagogastroduodenoscopy and histopathological sampling in our hospital between January and June 2023. The study included 79 patients aged between 18 and 85 years. The patients were categorized into two groups: 35 patients in the ICU with mechanical ventilation (MV) support (EMV) and 44 patients who presented to the gastroenterology department due to dyspeptic symptoms and underwent endoscopy (ED). Age; sex characteristics; laboratory parameters such as hemoglobin (Hb), hematocrit (Htc), mean cellular volume (MCV), white blood cell (WBC), neutrophil, platelet, glucose, urea, creatinine, aspartate transaminase (AST), alanine transaminase (ALT), C-reactive protein (CRP), albumin, ferritin, thyroid-stimulating hormone (TSH), anti-hepatitis C virus (HCV), hepatitis B surface antigen (HBsAg), anti-HIV; and biopsy results (H. pylori positivity, intestinal metaplasia, and atrophy) were recorded. Results A total of 79 patients who underwent gastric biopsy were assessed. There were 35 patients in the EMV group and 44 patients in the ED group. There was no difference in gender and age distribution between the groups. Hb and Htc were significantly lower in EMV compared to ED (p=0.001). Hb was 9.4±1.7 g/dL in EMV and 10.8±2.1 g/dL in ED. Htc was 29.6±5.1 in EMV and 33.5±5.7 in ED. MCV, WBC, glucose, urea, AST, ALT, CRP, and ferritin values were statistically significantly higher in EMV (p<0.05). Albumin and creatinine levels were statistically significantly lower in EMV (p<0.05). There was no significant difference between the groups in terms of neutrophils, platelets, and TSH. In the EMV group, H. pylori activity was negative in 31 (88.6%) patients and positive in four (11.4%) patients. In the ED group, H. pylori activity was negative in 30 (68.2%) patients and positive in 14 (31.8%) patients. There was a statistically significant difference between the groups in terms of H. pylori positivity (p=0.032). Conclusions The prevalence of H. pylori in MV patients in the ICU is low compared to the average population. The incidence of atrophic gastritis and intestinal metaplasia is the same. The present study supports that ICU cases do not have a higher risk of gastric premalignant lesions compared to the average population.

Enhanced multi-class pathology lesion detection in gastric neoplasms using deep learning-based approach and validation

This study developed a new convolutional neural network model to detect and classify gastric lesions as malignant, premalignant, and benign. We used 10,181 white-light endoscopy images from 2606 patients in an 8:1:1 ratio. Lesions were categorized as early gastric cancer (EGC), advanced gastric cancer (AGC), gastric dysplasia, benign gastric ulcer (BGU), benign polyp, and benign erosion. We assessed the lesion detection and classification model using six-class, cancer versus non-cancer, and neoplasm versus non-neoplasm categories, as well as T-stage estimation in cancer lesions (T1, T2-T4). The lesion detection rate was 95.22% (219/230 patients) on a per-patient basis: 100% for EGC, 97.22% for AGC, 96.49% for dysplasia, 75.00% for BGU, 97.22% for benign polyps, and 80.49% for benign erosion. The six-class category exhibited an accuracy of 73.43%, sensitivity of 80.90%, specificity of 83.32%, positive predictive value (PPV) of 73.68%, and negative predictive value (NPV) of 88.53%. The sensitivity and NPV were 78.62% and 88.57% for the cancer versus non-cancer category, and 83.26% and 89.80% for the neoplasm versus non-neoplasm category, respectively. The T stage estimation model achieved an accuracy of 85.17%, sensitivity of 88.68%, specificity of 79.81%, PPV of 87.04%, and NPV of 82.18%. The novel CNN-based model remarkably detected and classified malignant, premalignant, and benign gastric lesions and accurately estimated gastric cancer T-stages.

Usefulness of chorionic gonadotropin in premalignant gastric lesions

Usefulness of chorionic gonadotropin in premalignant gastric lesions

Does Portal Hypertension Increase the Risk of Helicobacter pylori Infection and Pre-Malignant Gastric Lesions?

Background and Aims: The presence of portal hypertension in cirrhotic patients is a major prognostic factor associated with the development of severe complications and increased mortality. The gold standard for diagnosing portal hypertension is the hepatic venous pressure gradient. More recently, spleen stiffness has emerged as a new and non-invasive diagnostic tool, and has already been included in the last Baveno VII guidelines. The exact prevalence of Helicobacter pylori infection, pre-malignant lesions and their relation to portal hypertension have never been described. The aim of our study was to evaluate the relationship between the presence of portal hypertension assessed via liver and spleen elastography and Helicobacter pylori infection and pre-malignant gastric lesions. Methods: An observational study was conducted, including consecutive patients admitted from December 2020 to December 2022. All patients underwent upper endoscopy and were also subjected to liver and spleen elastography (using the new probe of 100 Hz) by the same blinded operator in a tertiary center. Results: We included 155 cirrhotic patients, with a mean age of 64.1 years (±8.8), and 81.3% were male. The most common etiology was alcoholic liver disease (72.9%). The median value of liver stiffness measurement was 24.4 kPa [3.1-75.0], and the spleen stiffness measurement was 49.1 kPa [12.8-100.0]. Akin to endoscopic findings, 50.3% presented esophageal varices, 5.2% gastric atrophy, 11.6% gastric metaplasia, and 32.9% portal hypertension gastropathy. Regarding histologic findings, we found that 34.8% presented H. pylori infection, 35.5% gastric atrophy (OLGA 1-58.2%) and 38.7% gastric metaplasia (OLGIM 1-63.3%). Liver stiffness and spleen stiffness measurements were associated with the presence of portal hypertensive gastropathy (p < 0.01), but not with H. pylori infection or pre-malignant gastric lesions. Conclusions: Although present in almost one third of cirrhotic patients, H. pylori infection and pre-malignant gastric lesions are not associated with liver stiffness and spleen stiffness measurements. On the other hand, we found an association between liver stiffness and spleen stiffness measurements and portal hypertensive gastropathy.

Inflammatory microenvironment in gastric premalignant lesions: implication and application.

Gastric precancerous lesions (GPL) are a major health concern worldwide due to their potential to progress to gastric cancer (GC). Understanding the mechanism underlying the transformation from GPL to GC can provide a fresh insight for the early detection of GC. Although chronic inflammation is prevalent in the GPL, how the inflammatory microenvironment monitored the progression of GPL-to-GC are still elusive. Inflammation has been recognized as a key player in the progression of GPL. This review aims to provide an overview of the inflammatory microenvironment in GPL and its implications for disease progression and potential therapeutic applications. We discuss the involvement of inflammation in the progression of GPL, highlighting Helicobacter pylori (H. pylori) as a mediator for inflammatory microenvironment and a key driver to GC progression. We explore the role of immune cells in mediating the progression of GPL, and focus on the regulation of inflammatory molecules in this disease. Furthermore, we discuss the potential of targeting inflammatory pathways for GPL. There are currently no specific drugs for GPL treatment, but traditional Chinese Medicine (TCM) and natural antioxidants, known as antioxidant and anti-inflammatory properties, exhibit promising effects in suppressing or reversing the progression of GPL. Finally, the challenges and future perspectives in the field are proposed. Overall, this review highlights the central role of the inflammatory microenvironment in the progression of GPL, paving the way for innovative therapeutic approaches in the future.

Gastric Cancer Prevention; Detection of Premalignant Gastric Lesions and Surveillance for Early Detection of Gastric Cancer in Low Incidence Countries

Gastric Cancer Prevention; Detection of Premalignant Gastric Lesions and Surveillance for Early Detection of Gastric Cancer in Low Incidence Countries

Replicative stress in gastroesophageal cancer is associated with chromosomal instability and sensitivity to DNA damage response inhibitors

Gastroesophageal adenocarcinoma (GEA) is an aggressive malignancy with chromosomal instability (CIN). To understand adaptive responses enabling DNA damage response (DDR) and CIN, we analyzed matched normal, premalignant, and malignant gastric lesions from human specimens and a carcinogen-induced mouse model, observing activation of replication stress, DDR, and p21 in neoplastic progression. In GEA cell lines, expression of DDR markers correlated with ploidy abnormalities, such as number of high-level focal amplifications and whole-genome duplication (WGD). Integrating TP53 status, ploidy abnormalities, and DDR markers into a compositive score helped predict GEA cell lines with enhanced sensitivity to Chk1/2 and Wee1 inhibition, either alone or combined with irinotecan (SN38). We demonstrate that Chk1/2 or Wee1 inhibition combined with SN38/irinotecan shows greater anti-tumor activity in human gastric cancer organoids and an invivo xenograft mouse model. These findings indicate that specific DDR biomarkers and ploidy abnormalities may predict premalignant progression and response to DDR pathway inhibitors.

Epidemiology, Risk Factors for Gastric Cancer and Surveillance of Premalignant Gastric Lesions: A Prospective Cohort Study of Central Saudi Arabia.

(1) Background: Saudi Arabia (SA) is a country with a low incidence of gastric cancer (GC). In this study, we sought to assess the epidemiology of GC, its clinicopathological profiles, and its association with risk factors as well as to identify premalignant gastric lesions (PGL) and examine neoplastic progression. (2) Methods: This five-year prospective study screened for GC and PGL in asymptomatic Saudi patients, aged 45-75 years (n = 35,640) and living in Al Kharj, Riyadh province in central SA. Those who were positive in a high-sensitivity guaiac fecal occult blood test (HSgFOBT+) and had negative results in colonoscopy offered to undergo upper GI endoscopy (n = 1242). Factors associated with GC were examined. (3) Results: The five-year participation rate was 87% (1080/1242). The incidence rate of GC was 26.9 new cases per 100,000 population per year (9.6 new cases per year/total population at risk-35,640), and it was 8.9 cases per 1000 persons per year among the 1080 subjects with HSgFOBT+ and negative colonoscopy results. The five-year mortality rate was 67% among patients with GC (n = 48), 3.0% among participants in the gastric screening program (n = 1080) and 0.09% among the original population participating in the colorectal screening program (n = 35,640). Intestinal-type adenocarcinoma was the most frequent type (77%), with the tumor most commonly located in the antrum (41%). Overall, 334 participants had PGL, and seven of them (2.1%) showed neoplastic progression to GC during the follow-up. Factors associated with GC were age, Helicobacter pylori (HP) infection, obesity (body mass index BMI > 30), smoking, a diet of salty preserved foods, low income and a family history of GC. (4) Conclusions: The incidence of GC is low in central SA, but screening for PGL and GC among patients with HSgFOBT+ and negative colonoscopy may prevent or result in the early treatment of GC. HP eradication, normal body weight, not smoking and adhering to a healthy diet can reduce the risk of GC. The resulting data provide important input for the improvement of national guidelines.

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

The online version contains supplementary material available at 10.1007/s43657-023-00118-w.

Predictors of anemia without active bleeding signs in patients referred for endoscopy

Abstract Objective: The objective of the present study is to clarify the value of clinic, endoscopic, and histologic variables that may predict anemia in patients performing esophagogastroduodenoscopy for gastrointestinal complaints in the absence of bleeding signs or lower digestive disease. Methods: This study included 654 patients referred for endoscopy that were divided based on biological parameters performed in the same day in the study group (306 patients diagnosed with anemia) and the control group (348 patients without anemia). Results: Anemia is frequent in elderly patients, especially in the presence of premalignant gastric lesions, and it is associated with multiple comorbidities. In two multivariate regression models antivitamin K oral anticoagulants were found to be independently associated with anemia (p = 0.01), but not with antiplatelet therapy, or with non-antivitamin K anticoagulants. Multiple regression models support that epigastric pain and heartburn are inversely associated with anemia, while weight loss remained an independent predictor for simultaneous anemia and premalignant lesions. Non-infectious chronic gastritis (p&lt;0.001) is an independent predictor for anemia and premalignant gastric lesions, increasing the odds of anemia by 2.2 times, while reactive gastropathy is inversely associated. Gastric erosions and ulcer remained independent predictors for concomitant anemia and premalignant lesions. Conclusions: Chronic inactive gastritis and premalignant gastric histologic lesions are predictors for anemia in endoscopic population, while active H. pylori infection is not. Dyspeptic symptoms, epigastric pain (p&lt;0.001,OR 0.2-0.5) and heartburn (p&lt;0.001,OR 0.07-0.3) are inversely associated with anemia alone or associated with premalignant gastric lesions.

Role of salivary miRNAs in the diagnosis of gastrointestinal disorders: a mini-review of available evidence.

MiRNAs are short, non-coding RNA molecules, which are involved in the regulation of gene expression and which play an important role in various biological processes, including inflammation and cell cycle regulation. The possibility of detecting their extracellular expression, within body fluids, represented the main background for their potential use as non-invasive biomarkers of various diseases. Salivary miRNAs particularly gained interest recently due to the facile collection of stimulated/unstimulated saliva and their stability among healthy subjects. Furthermore, miRNAs seem to represent biomarker candidates of gastrointestinal disorders, with miRNA-based therapeutics showing great potential in those conditions. This review aimed to highlight available evidence on the role of salivary miRNAs in different gastrointestinal conditions. Most salivary-based miRNA studies available in the literature that focused on pathologies of the gastrointestinal tract have so far been conducted on pancreatic cancer patients and delivered reliable results. A few studies also showed the diagnostic utility of salivary miRNAs in conditions such as esophagitis, esophageal cancer, colorectal cancer, or inflammatory bowel disease. Moreover, several authors showed that salivary miRNAs may confidently be used as biomarkers of gastric cancer, but the use of salivary miRNA candidates in gastric inflammation and pre-malignant lesions, essential stages of Correa's cascade, is still put into question. On the other hand, besides miRNAs, other salivary omics have shown biomarker potential in gastro-intestinal conditions. The limited available data suggest that salivary miRNAs may represent reliable biomarker candidates for gastrointestinal conditions. However, their diagnostic potential requires validation through future research, performed on larger cohorts.

Endoscopic Resection of Early Gastric Cancer and Pre-Malignant Gastric Lesions.

Early gastric cancer comprises gastric malignancies that are confined to the mucosa or submucosa, irrespective of lymph node metastasis. Endoscopic resection is currently pivotal for the management of such early lesions, and it is the recommended treatment for tumors presenting a very low risk of lymph node metastasis. In general, these lesions consist of two groups of differentiated mucosal adenocarcinomas: non-ulcerated lesions (regardless of their size) and small ulcerated lesions. Endoscopic submucosal dissection is the technique of choice in most cases. This procedure has high rates of complete histological resection while maintaining gastric anatomy and its functions, resulting in fewer adverse events than surgery and having a lesser impact on patient-reported quality of life. Nonetheless, approximately 20% of resected lesions do not fulfill curative criteria and demand further treatment, highlighting the importance of patient selection. Additionally, the preservation of the stomach results in a moderate risk of metachronous lesions, which underlines the need for surveillance. We review the current evidence regarding the endoscopic treatment of early gastric cancer, including the short-and long-term results and management after resection.

The effectiveness of a computer-aided system in improving the detection rate of gastric neoplasm and early gastric cancer: study protocol for a multi-centre, randomized controlled trial

BackgroundThis protocol is for a multi-centre randomised controlled trial to determine whether the computer-aided system ENDOANGEL-GC improves the detection rates of gastric neoplasms and early gastric cancer (EGC) in routine oesophagogastroduodenoscopy (EGD).MethodsStudy design: Prospective, single-blind, parallel-group, multi-centre randomised controlled trial.Settings: The computer-aided system ENDOANGEL-GC was used to monitor blind spots, detect gastric abnormalities, and identify gastric neoplasms during EGD.Participants: Adults who underwent screening, diagnosis, or surveillance EGD.Randomisation groups:1. Experiment group, EGD examinations with the assistance of the ENDOANGEL-GC;2. Control group, EGD examinations without the assistance of the ENDOANGEL-GC.Randomisation: Block randomisation, stratified by centre.Primary outcomes: Detection rates of gastric neoplasms and EGC.Secondary outcomes: Detection rate of premalignant gastric lesions, biopsy rate, observation time, and number of blind spots on EGD.Blinding: Outcomes are undertaken by blinded assessors.Sample size: Based on the previously published findings and our pilot study, the detection rate of gastric neoplasms in the control group is estimated to be 2.5%, and that of the experimental group is expected to be 4.0%. With a two-sided α level of 0.05 and power of 80%, allowing for a 10% drop-out rate, the sample size is calculated as 4858. The detection rate of EGC in the control group is estimated to be 20%, and that of the experiment group is expected to be 35%. With a two-sided α level of 0.05 and power of 80%, a total of 270 cases of gastric cancer are needed. Assuming the proportion of gastric cancer to be 1% in patients undergoing EGD and allowing for a 10% dropout rate, the sample size is calculated as 30,000. Considering the larger sample size calculated from the two primary endpoints, the required sample size is determined to be 30,000.DiscussionThe results of this trial will help determine the effectiveness of the ENDOANGEL-GC in clinical settings.Trial registrationChiCTR (Chinese Clinical Trial Registry), ChiCTR2100054449, registered 17 December 2021.

Abstract 1194: Evolution of immune and stromal cell states during the gastric cancer continuum

Abstract Introduction: Gastric adenocarcinoma (GAC), a global health burden, lacks detail understanding of the evolution-driven cellular/molecular programs that lead to GAC tumorigenesis followed by progression/metastases. How the TME is orchestrated by precancerous lesions, primary GAC, and in metastatic niches, when well understood, may propel us into an entirely new dimension with the hopes of novel therapeutics. However, only a few studies have investigated the immune/stromal subtypes of GAC with the limitation of scope, cohort size, and/or depth or mainly focused on the primary GACs. Here, we present an atlas of transcriptionally diverse TME across the full continuum of GAC by including peripheral blood, normal gastric tissues, premalignant lesions, localized, and metastatic GACs. Methods: We performed a comprehensive single-cell profiling of 68 specimens collected from 43 subjects including a total of 77,392 high-quality cells which revealed 62 unique cell states uncovering varying profiles. We defined alterations in TMEs that underscore initiation of tumorigenesis to eventual progression. Results: We found a striking preponderance of B lineage cells, primarily the IgA+ plasma cells, in TMEs of the precancerous lesions, whereas 3 immunosuppressive myeloid subsets dominated in advanced GACs. Fractions of GZMK+ effector CD8 T cells and progenitor exhausted CD8 T cells gradually increased as GACs progressed to advanced stages. In addition, our analysis revealed extensive stromal remodeling along the GAC continuum, which may have contributed to enhanced angiogenesis and immune suppressive signaling. The observations in the primary tumors could be validated in an independent scRNA-seq dataset. Notably, we uncovered 3 unique TME interactomes and defined 6 cellular environtypes inhabited by 62 TME cell subsets giving GAC to a novel landscape not yet defined. The two distinct environtypes in GAC primaries are validated in three independent large-scale GAC cohorts, giving credence and definition to previously established histopathological variables, genomic/molecular subtypes and clinical outcomes. The analysis of tumor associated stromal cells discovered SDC2 as an exploitable target to pursue. SDC2 was abundant in cancer associated fibroblasts (CAFs), and the abundance is validated in 3 independent single-cell GAC cohorts as well as at the protein level. SDC2 expression was significantly higher in advanced (vs. early) stages and diffuse (vs. intestinal) type of GAC, and SDC2 overexpression was associated with shorter survival in all 5 large-scale GAC cohorts. Lastly, we assessed the functional effects of SDC2 expression in CAFs on tumor growth in vivo in xenograft models and found SDC2 overexpression in CAFs contributes to tumor growth. Conclusion: This study provides an atlas of GAC TMEs from tumorigenesis to advanced GAC that could be further developed for novel therapeutics but also serves as a community resource. Citation Format: Ruiping Wang, Shumei Song, Jiangjiang Qin, Katsuhiro Yoshimura, Fuduan Peng, Yanshuo Chu, Yuan Li, Yibo Fan, Jiankang Jin, Minghao Dang, Enyu Dai, Guangsheng Pei, Guangchun Han, Yating Li, Deyali Chatterjee, Melissa P. Pizzi, Ailing W. Scott, Ghia Tatlonghari, Xinmiao Yan, Matheus Da Silva Sewastjanow, Ahmed Adel Fouad Abdelhakeem, Pawel K. Mazur, Xiangdong Cheng, Jaffer A. Ajani, Linghua Wang. Evolution of immune and stromal cell states during the gastric cancer continuum [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1194.

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.

Endoscopic advances in the management of gastric cancer and premalignant gastric conditions.

Gastric cancer is the fifth most common cancer and in 2018, it was the third most common cause of cancer-related deaths worldwide. Endoscopic advances continue to be made for the diagnosis and management of both early gastric cancer and premalignant gastric conditions. In this review, we discuss the epidemiology and risk factors of gastric cancer and emphasize the differences in early vs late-stage gastric cancer outcomes. We then discuss endoscopic advances in the diagnosis of early gastric cancer and premalignant gastric lesions. This includes the implementation of different imaging modalities such as narrow-band imaging, chromoendoscopy, confocal laser endomicroscopy, and other experimental techniques. We also discuss the use of endoscopic ultrasound in the diagnosis and staging of early gastric cancer. We then discuss the endoscopic advances made in the treatment of these conditions, including endoscopic mucosal resection, endoscopic submucosal dissection, and hybrid techniques such as laparoscopic endoscopic cooperative surgery. Finally, we comment on the current suggested recommendations for surveillance of both gastric cancer and its premalignant conditions.

Increased IL-17A Serum Levels and Gastric Th17 Cells in Helicobacter pylori-Infected Patients with Gastric Premalignant Lesions

Background:Helicobacter pylori infection is characterized by an inflammatory infiltrate that might be an important antecedent of gastric cancer. The purpose of this study was to evaluate whether interleukin (IL)-17 inflammation is elicited by gastric T cells in Helicobacter pylori patients with gastric intestinal metaplasia and dysplasia (IM/DYS). We also investigated the serum IL-17A levels in Helicobacter pylori patients with gastric intestinal metaplasia and dysplasia, and patients with Helicobacter pylori non-atrophic gastritis (NAG). Methods: the IL-17 cytokine profile of gastric T cells was investigated in six patients with IM/DYS and Helicobacter pylori infection. Serum IL-17A levels were measured in 45 Helicobacter pylori-infected IM/DYS patients, 45 Helicobacter pylori-infected patients without IM/DYS and in 45 healthy controls (HC). Results: gastric T cells from all IM/DYS patients with Helicobacter pylori were able to proliferate in response to Helicobacter pylori and to produce IL-17A. The Luminex analysis revealed that IL-17A levels were significantly increased in Helicobacter pylori IM/DYS patients compared to healthy controls and to Helicobacter pylori gastritis patients without IM/DYS (452.34 ± 369.13 pg/mL, 246.82 ± 156.06 pg/mL, 169.26 ± 73.82 pg/mL, respectively; p < 0.01, p < 0.05). Conclusions: the results obtained indicate that Helicobacter pylori is able to drive gastric IL-17 inflammation in IM/DYS Helicobacter pylori-infected patients, and that IL-17A serum levels are significantly increased in Helicobacter pylori-infected patients with IM/DYS.

Phylogenetic origin of Helicobacter pylori pathogenicity island and risk of stomach cancer and high-grade premalignant gastric lesions.

Infection by Helicobacter pylori (Hp) has been causally linked to risk of gastric cancer (GC). The coevolution of Hp and humans shaped the risk of GC as our species left Africa and migrated to the other continents. Latin America (LatAm) is a high GC incidence region where Hp evolved uniquely in the 500 years since European colonization. Differential virulence of the Hp cagA -pathogenicity island (cagPAI) by ancestral origin has been reported. We hypothesized that Hp phylogenetic origin might play a role in determining GC risk in LatAm. We used genotypes of 50 Hp genetic variants mapping to the Hp cagPAI, studied in 1220 subjects from Venezuela, Colombia, Mexico and Paraguay, who were infected with cagA-positive Hp, including 150 GC, 177 high-grade premalignant lesions (HGPMLs) and 893 low-grade premalignant lesions. We estimated the phylogenetic origin of Hp cagPAI in all study subjects by use of the STRUCTURE software and principal component analysis (PCA) and tested whether the estimated African ancestry percentage was associated with the risk of GC or HGPML. African ancestral component estimates by STRUCTURE and PCA were highly correlated. STRUCTURE-based African origin estimate was not significantly associated with the risk of HGPML, but it was inversely associated with GC risk: the OR associated with the continuous values of African component was 0.09 (95% CI, 0.01-0.85; P = 0.035). Similar trends were observed for GC with PCA-based estimates, but the association was not statistically significant. These results suggest that Hp ancestral origin may play a role in gastric carcinogenesis.

Helicobacter pylori-Positive Gastric Biopsies-Association with Clinical Predictors.

Introduction: Although Helicobacter pylori’s role in gastric oncogenesis is well-known, only a fraction of infected patients develop cancer. Hence, more factors are supposed to be involved. The objectives of the present study were to investigate the impact of clinicopathological parameters on Helicobacter pylori status. Methods: The study included 1522 patients referred for endoscopy: study group consisted of 557 patients with Helicobacter pylori-positive biopsies confirmed using histochemical stains or immunohistochemistry methods; and the control group consisted of 965 patients with Helicobacter pylori-negative status on histology. Results: Severe endoscopic lesions were more frequent in the Helicobacter pylori group (p < 0.001), with no difference noticed in the distribution of premalignant gastric lesions (p = 0.82). Anemia and dyslipidemia were independent factors associated with Helicobacter pylori-positive biopsies (p < 0.05). Non-steroidal anti-inflammatory therapy was more frequently administered in the study group, while proton-pump inhibitors had an anti-Helicobacter pylori activity on histology (p < 0.0001). Conclusion: In the studied population, patients with Helicobacter pylori-positive biopsies had a more frequent history of gastrotoxic medication, severe endoscopic lesions, and anemia. Helicobacter pylori was unpredictable by gastrointestinal symptoms. The frequency of premalignant gastric lesions was similar irrespective of the actual status of infection, underlining the importance of unintentional clearance of bacteria in old infection and the remaining risk for cancer in this population.