A multi-omics study to investigate the progression of the Correa pathway in gastric mucosa in the context of cirrhosis.

BACKGROUND: Patients with liver cirrhosis (LC) are prone to gastric mucosa damage. We investigated the alterations of gastric mucosa in LC patients and their possible mechanisms through multi-omics. RESULTS: We observed significant gastric mucosa microbial dysbiosis in LC subjects. Gastric mucosal microbiomes of LC patients contained a higher relative abundance of Streptococcus, Neisseria, Prevotella, Veillonella, and Porphyromonas, as well as a decreased abundance in Helicobacter and Achromobacter, than control subjects. The LC patients had higher levels of bile acids (BAs) and long-chain acylcarnitines (long-chain ACs) in serum. The gastric mucosal microbiomes were associated with serum levels of BAs and long-chain ACs. Transcriptome analyses of gastric mucosa revealed an upregulation of endothelial cell specific molecule 1, serpin family E member 1, mucin 2, caudal type homeobox 2, retinol binding protein 2, and defensin alpha 5 in LC group. Besides, the bile secretion signaling pathway was significantly upregulated in the LC group. CONCLUSIONS: The alterations in the gastric mucosal microbiome and transcriptome of LC patients were identified. The impaired energy metabolism in gastric mucosal cells and bile acids might aggravate the inflammation of gastric mucosa and even exacerbate the Correa's cascade process. The gastric mucosal cells might reduce bile acid toxicity by bile acid efflux and detoxification. TRIAL REGISTRATION: ChiCTR2100051070.

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.

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.

Genetic polymorphisms in the cag pathogenicity island of Helicobacter pylori and risk of stomach cancer and high-grade premalignant gastric lesions.

Helicobacter pylori (Hp) infects the stomach of about half of the human population and is strongly associated with the risk of gastric cancer (GC) and its premalignant precursors. The cag pathogenicity island (cagPAI) is a region of the Hp genome encoding for key molecular machinery involved in the infection process. Following a sequencing study, we selected 50 genetic polymorphisms located in seven cagPAI genes and tested their associations with the risk of advanced gastric premalignant lesions and GC in 1220 subjects from various Latin American populations showing the whole spectrum of phenotypes from gastritis to GC. We found that three polymorphisms of cagA are associated with the risk of advanced gastric premalignant lesions (incomplete intestinal metaplasia [ie, Type 2 and 3] or dysplasia), and that six polymorphisms located in cagA, cagL and cagI were associated with risk of GC. When corrected for multiple testing none of the associations were statistically significant. However, scores built by integrating the individual polymorphisms were significantly associated with the risk of advanced gastric premalignant lesions and GC. These results have the potential of establishing markers for risk stratification in the general population, in view of targeting Hp eradication to high-risk population groups.

Surveillance of premalignant gastric lesions: a multicentre prospective cohort study from low incidence regions.

OBJECTIVE: International guidelines recommend endoscopic surveillance of premalignant gastric lesions. However, the diagnostic yield and preventive effect require further study. We therefore aimed to assess the incidence of neoplastic progression and to assess the ability of various tests to identify patients most at risk for progression. DESIGN: Patients from the Netherlands and Norway with a previous diagnosis of atrophic gastritis (AG), intestinal metaplasia (IM) or dysplasia were offered endoscopic surveillance. All histological specimens were assessed according to the updated Sydney classification and the operative link on gastric intestinal metaplasia (OLGIM) system. In addition, we measured serum pepsinogens (PG) and gastrin-17. RESULTS: 279 (mean age 57.9 years, SD 11.4, male/female 137/142) patients were included and underwent at least one surveillance endoscopy during follow-up. The mean follow-up time was 57 months (SD 36). Four subjects (1.4%) were diagnosed with high-grade adenoma/dysplasia or invasive neoplasia (ie, gastric cancer) during follow-up. Two of these patients were successfully treated with endoscopic submucosal dissection, while the other two underwent a total gastrectomy. Compared with patients with extended AG/IM (PGI/II≤3 and/or OGLIM stage III-IV), patients with limited AG/IM (PG I/II>3 and OLGIM stage 0-II) did not develop high-grade adenoma/dysplasia or invasive neoplasia during follow-up (p=0.02). CONCLUSION: In a low gastric cancer incidence area, a surveillance programme can detect gastric cancer at an early curable stage with an overall risk of neoplastic progression of 0.3% per year. Use of serological markers in endoscopic surveillance programmes may improve risk stratification.

Meta-analysis: The diagnostic efficacy of chromoendoscopy for early gastric cancer and premalignant gastric lesions.

BACKGROUND AND AIM: Chromoendoscopy (CE) is widely used in the diagnosis of early gastric cancer (EGC) and premalignant gastric lesions (PGLs). We conducted a meta-analysis to evaluate the diagnostic efficacy of CE for EGC and PGLs. METHODS: We searched PubMed/MEDLINE, EMBASE, and the Cochrane library to identify all eligible studies according to inclusion and exclusion standards. Publication bias was tested using Funnel plots and Egger's test. The possible sources of the heterogeneity were explored by performing a meta-regression analysis. Heterogeneity was assessed by the Q test and I(2) statistic. RESULTS: Ten studies met the inclusion standards, including a total of 699 patients and 902 lesions. The pooled sensitivity, specificity, and area under the curve of CE were 0.90 (95% confidence interval, 0.87-0.92), 0.82 (95% confidence interval, 0.79-0.86), and 0.9464, respectively. In subgroup analysis of diagnostic accuracy, CE showed higher accuracy versus standard white light endoscopy for EGC (P = 0.005) and PGLs (P = 0.001). CONCLUSION: Chromoendoscopy seems to have a high diagnostic efficacy and improve the detection of EGC and PGLs compared with standard white light endoscopy.