Grade Of Gastric Atrophy Research Articles

Endoscopic gastric atrophy is strongly associated with gastric cancer development after Helicobacter pylori eradication

BackgroundRisk factors for gastric cancer during continuous infection with Helicobacter pylori have been well documented; however, little has been reported on the risk factors for primary gastric cancer after H. pylori eradication. We conducted a retrospective, endoscopy-based, long-term, large-cohort study to clarify the risk factors for gastric cancer following H. pylori eradication.MethodsPatients who achieved successful H. pylori eradication and periodically underwent esophagogastroduodenoscopy surveillance thereafter at Toyoshima Endoscopy Clinic were enrolled. The primary endpoint was the development of gastric cancer. Statistical analysis was performed using the Kaplan–Meier method and Cox’s proportional hazards models.ResultsGastric cancer developed in 15 of 1232 patients. The cumulative incidence rates were 1.0 % at 2 years, 2.6 % at 5 years, and 6.8 % at 10 years. Histology showed that all gastric cancers (17 lesions) in the 15 patients were of the intestinal type, within the mucosal layer, and <20 mm in diameter. Based on univariate analysis, older age and higher endoscopic grade of gastric atrophy were significantly associated with gastric cancer development after eradication of H. pylori, and gastric ulcers were marginally associated. Multivariate analysis identified higher grade of gastric atrophy (hazard ratio 1.77; 95 % confidence interval 1.12–2.78; P = 0.01) as the only independently associated parameter.ConclusionsEndoscopic gastric atrophy is a major risk factor for gastric cancer development after H. pylori eradication. Further long-term studies are required to determine whether H. pylori eradication leads to regression of H. pylori-related gastritis and reduces the risk of gastric cancer.

P57: The first Siberian experience of gastric cancer riskometry: Prospective “case-control” study

Gastric cancer (GC) remains one of the most important gastrointestinal cancers worldwide. The incidence and mortality rate from GC in Russia is higher in comparison with other European countries and USA. It should be noted that riskometry for the GC doesn’t exist. Parallel assessment of pepsinogen I (PG I), pepsinogen II (PG II), PG I/PG II ratio and gastrin-17 (G-17), as well as antibodies to Helicobacter pylori is an exact and validated set of stomach-specific biomarkers that reflect the extent and grade of gastric atrophy as a main premalignant condition for GC. To study the diagnostic and predicting value of biomarkers of atrophic gastritis (AG) in retro-prospective cohort case-control study in Siberian population. General population sample was surveyed in Novosibirsk in 2003–2005 (10.000 subjects aged 45–69 years). Each serum sample was deeply frozen and stored. In 2008 and 2012 this database was compared with the data of the Population Cancer Registry. As a result of cross-sectional analysis of two databases 60 novel cases of GC were identified until 2011. For each case of GC, an appropriate control case was selected at the ratio 1:2 matching the area of residence, sex and age. Finally, 156 serum samples (52 – GC group and 104 – control group) were available for the analysis using a panel of serum biomarkers “Gastropanel” (Biohit, Finland). Criteria for “Gastropanel” in the diagnosis of AG were used: PG I <30μg/l, PG II <3μg/l, the ratio PG I/PG II <3, the level of basal G-17<1 pmol/l, and the presence of antibodies to H. pylori. Mean level of biomarkers did not differ between those with, and without GC, with the exception for PG I/PGII ratio, which was significantly lower in GC group. Indicators of gastric atrophy (OR; 95% CI) were associated with GC for PG I (2.9; 1.3–6.4), PG II (9.0; 1.8–44.3), and PG I/PG II (3.3; 1.5–7.3), but neither for G-17 (0.7, 0.4–1.6), nor for the presence of antibodies to H. pylori (0.4; 0.1–1.3). Multivariate regression analysis including sex, age of the patients, all biomarkers of “Gastropanel” confirmed PG I and PGI/PGII ratio as the most powerful indicators in the model. Atrophy Index (AI) was calculated as a sum of abnormal parameters of gastric atrophy (PG I, PG I/PG II ratio and G-17, see Table, ∗p < 0.019; ∗∗p < 0.006). AI 3 (all biomarkers below normal range) was more common in GC patients than in controls. GroupsSeverity of atrophy (Atrophy Index score) (%)Empty Cell3210Gastric cancer14.0∗∗20.010.056.0Control2.210.811.875.3∗ As a first step in the development of GC riskometry was found that noninvasive set of serological biomarkers is an informative and non-expensive tool for the early detection of GC in population-based retrospective cohort survey in Siberian population. Low levels of PGI and PGI/PGII ratio were proven as the most valuable prognostic factors. The low level of G-17 as a single index did not significantly predict the risk of GC.

Slow Overmethylation of Housekeeping Genes in the Body Mucosa Is Associated with the Risk for Gastric Cancer

Helicobacter pylori infection increases age-related diverse overmethylation in gene-control regions, which increases the risk of gastric cancer. The H. pylori-associated overmethylation changes subsequently disappear when gastric atrophy and cancer develop. To identify cancer-risk epigenotypes, we traced dynamic methylation changes in the background mucosa of the stomach depending on the extent of gastric atrophy. Paired biopsy specimens were obtained from the noncancerous antrum and body mucosa of 102 patients with cancer and 114 H. pylori-positive and 112 H. pylori-negative controls. The grade of gastric atrophy was evaluated using the endoscopic atrophic border score. The methylation-variable sites at the CpG-island margins and near the transcriptional start sites lacking CpG islands were semiquantitatively analyzed by radioisotope-labeling methylation-specific PCR. We selected eight housekeeping genes adjacent to Alu (CDH1, ARRDC4, PPARG, and TRAPPC2L) or LTR retroelements (MMP2, CDKN2A, RUNX2, and RUNX3) and eight stomach-specific genes (TFF2, PGC, ATP4B, TFF1, TFF3, GHRL, PGA, and ATP4A). Analysis of age-related methylation in the H. pylori-positive controls revealed slow overmethylation in the body and in the LTR-adjacent genes. A high-frequency overmethylation defined based on the slowly overmethylated genes was frequently observed in the body of patients with gastric cancer with open-type atrophy (OR, 12.7; 95% confidence interval, 3.2-49.8). The rapidly changing methylation of Alu-adjacent genes was barely increased in the antrum of patients with gastric cancer. Among diverse methylation changes associated with H. pylori infection, an increase in slowly changing methylation could serve as a cancer-risk marker.

CD44 variant 9 expression in primary early gastric cancer as a predictive marker for recurrence

Background:Multiple early gastric cancers (EGCs) may develop in 6–14% of patients even after achieving curative endoscopic submucosal dissection (ESD); however, a useful biomarker for predicting recurrence is not available. The present study investigated whether the expression of CD44 variant 9 (CD44v9), a functional cancer stem cell marker, in the primary gastric cancer tissue represents an indicator of recurrence.Methods:Eighty-eight patients who underwent ESD for EGC from 2008 to 2010 were enrolled and monitored for recurrence for 3 years. The expression levels of CD44v9 in the tissue of initial EGCs were evaluated by immunohistochemistry, and the recurrence rate was compared between CD44v9-positive and CD44v9-negative groups. The mucin phenotype and expression of microRNA-21 (miR-21) and programmed cell death protein 4 (PDCD4) were also analysed.Results:The recurrence rate of EGC was significantly higher in the CD44v9-positive group than in the CD44v9-negative group (hazard ratio (HR), 21.8; 95% confidence interval (CI), 5.71–83.1). However, mucin phenotypes and the expression of miR-21 and PDCD4 did not predict recurrence after ESD. Meanwhile, grade of gastric atrophy was also identified as a significant marker of multiple recurrence (HR, 4.95; 95% CI, 1.30–18.8).Conclusion:CD44 variant 9 expression represents a potential predictive marker for recurrence in EGC.

When Does Gastric Atrophy Develop in Japanese Children?

Long-term Helicobacter pylori infection causes inflammatory sequelae such as atrophy and intestinal metaplasia in the stomach, which is thought to increase the risk of developing gastric malignancy. We previously reported that gastric atrophy can develop in Japanese children with H. pylori infection, predominantly in the antrum. However, detailed data about the age of children with atrophy are largely lacking. In the present study, 131 children (79 boys) with H. pylori infection were re-analyzed for an association between age and the grade of gastric atrophy. The gastric antrum was histologically evaluated in all 131 patients and the corpus in 46 patients. Grade 2 and 3 antral atrophy was observed in 13 and one patients, respectively: the mean age was 12.1 years. Two patients (11 and 14 years old) had grade 2 corpus atrophy but no patients had grade 3. No significant difference was found in age among patients with grade 0, 1 and 2 or 3 atrophy in the antrum (p = .97) and in the corpus (p = .59). None of the patients with grade 2 or 3 atrophy had intestinal metaplasia either in the antrum or in the corpus. The results of the present study require a careful interpretation because of the retrospective analysis. In high-risk countries of gastric cancer, however, eradicating H. pylori in childhood could prove more effective in preventing gastric atrophy, ultimately, the development of cancer.

Baseline gastric mucosal atrophy is a risk factor associated with the development of gastric cancer after Helicobacter pylori eradication therapy in patients with peptic ulcer diseases

We previously reported that eradication of Helicobacter pylori could reduce the risk of developing gastric cancer in patients with peptic ulcer diseases. In the present study, we further followed up our patient groups to identify factors associated with the development of gastric cancer. Prospective posteradication evaluations were conducted in 1342 consecutive patients (1191 men and 151 women; mean age, 50 years) with peptic ulcer disease who had received H. pylori eradication therapy. The patients had undergone endoscopic examination before eradication therapy to evaluate peptic ulcers, background gastric mucosa, and H. pylori infection. After confirmation of eradication, follow-up endoscopy was performed yearly. A total of 1131 patients were followed for up to 9.5 years (mean, 3.9 years). Gastric cancer developed in 9 of 953 patients cured of infection and in 4 of 178 who had persistent infection (P=0.04). The risk of developing gastric cancer after receiving H. pylori eradication therapy was increased according to the grade of baseline gastric mucosal atrophy (P=0.01). In patients with peptic ulcer diseases, persistent infection of H. pylori (hazard ratio, 3.9; P=0.03), the grade of baseline gastric mucosal atrophy (3.3, P=0.01) and age (2.0, P=0.04) were identified as significant risk factors for developing gastric cancer. The grade of gastric atrophy was closely related to the development of gastric cancer after receiving H. pylori eradication therapy. Thus, eradication of H. pylori before the significant expansion of atrophy is most beneficial to prevent gastric cancer.

Relationship between IL-1β gene polymorphism and gastric mucosal IL-1β levels in patients with Helicobacter pylori infection

Interkeukin-1 (IL-1) gene cluster polymorphisms that are thought to enhance the production of IL-1beta are associated with an increased risk of gastric cancer. To determine the role of host genetic factors in Helicobacter pylori infection, we examined the relationship between gastric mucosal IL-1beta levels and IL-1B polymorphisms in patients with H. pylori infection. Biopsy tissues obtained from 99 patients were homogenized and gastric mucosal IL-1beta levels were measured by enzyme-linked immunosorbent assay (ELISA). Single-base polymorphisms at positions -511 and -31 in IL-1B were analyzed. The IL-1beta level in the antrum was significantly higher in genotype IL-1B-511C/C than in H. pylori-negative patients (P < 0.05). The IL-1B polymorphism did not influence the degree of gastric neutrophil and mononuclear cell infiltration, or gastric atrophy. IL-1beta levels in the corpus, but not those in the antrum, correlated to the severity of gastric atrophy. These findings indicate that IL-1B polymorphisms enhance IL-1beta production in the antrum; however, other factors might regulate the production of IL-1beta in the corpus of the stomach, regardless of IL-1B polymorphisms, and high IL-1beta production may be associated with the grade of gastric atrophy in the corpus mucosa in patients with H. pylori infection.

Agreement between endoscopic and histological gastric atrophy scores

This study was conducted to investigate the strength of agreement between the endoscopic atrophic border (EAB) and the histological score for atrophy. A series of 298 dyspeptic Japanese patients underwent upper endoscopy. The grade of gastric atrophy was estimated according to the EAB. Antral and corpus biopsy specimens were taken and were evaluated semiquantitatively according to the updated Sydney classification system, including the score for atrophy. The StatExact software package was used to calculate the weighted kappa statistics. The strength of agreement between the endoscopic atrophy score (EAB) and the histological atrophy score was good, with a weighted kappa value of 0.51 (95% confidence interval, 0.44-0.59). The strength of agreement between the endoscopic and histological atrophy scores is not worse than the interobserver histological agreement between two pathologists. It is worthwhile to carry out further research on the use of the EAB to identify and score gastric atrophy.