IntroductionPopulation-based eradication of Helicobacter pylori has been suggested to be cost-effective and is recommended by international guidelines. However, the potential adverse effects of widespread antibiotic use that this would entail have not been sufficiently studied. An alternative way to decrease gastric cancer mortality is by non-invasive search for precancerous lesions, in particular gastric atrophy; pepsinogen tests are the best currently available alternative. The primary objective of GISTAR is to determine whether H pylori eradication combined with pepsinogen testing reduces mortality from gastric cancer among 40–64-year-old individuals. The secondary objectives include evaluation of H pylori eradication effectiveness in gastric cancer prevention in patients with precancerous lesions and evaluation of the potential adverse events, including effects on microbiome.Methods and analysisIndividuals are recruited from general population (50% men) in areas with high gastric cancer risk in Europe and undergo detailed lifestyle and medical history questionnaire before being randomly allocated to intervention or control groups. The intervention group undergoes H pylori testing and is offered eradication therapy if positive; in addition, pepsinogen levels are detected in plasma and those with decreased levels are referred for upper endoscopy. All participants are offered faecal occult blood testing as an incentive for study participation. Effectiveness of eradication and the spectrum of adverse events are evaluated in study subpopulations. A 35% difference in gastric cancer mortality between the groups is expected to be detectable at 90% power after 15 years if 30 000 individuals are recruited. Biological materials are biobanked for the main and ancillary studies. The study procedure and assumptions will be tested during the pilot phase.Ethics and disseminationThe study was approved by the respective ethics committees. An independent Data Safety and Monitoring Board has been established. The findings will be published in peer-reviewed journals and presented at scientific meetings.Trial registration numberNCT02047994

We aimed to determine the diagnostic value of anti-parietal cell antibodies (anti-PCA), anti-intrinsic factor antibodies (anti-IFA), pepsinogen ratio (PGI/II), and gastrin-17 (G-17) in corpus-restricted atrophic gastritis (CRAG) detected by ELISA (Inova, Biohit). Our study compared 29 CRAG cases against 58 age- and sex-matched controls with mild or no atrophy. Anti-PCA and anti-IFA positive cutoff values were ≥25 units for both. PGI/II value <3 was considered characteristic for atrophy; positive cutoff values for G-17 and anti-H. pylori IgG were >5 pg/L and >30 EIU. Anti-PCA was positive in 65.5% For CRAG cases and 13.8% of the controls (p < 0.0001), anti-IFA was positive in 13.8% and 0% (p = 0.01), respectively. Decreased pepsinogen levels were present in 79.3% of CRAG cases and 10.3% of the controls (p < 0.0001). PGI/II ratio was the best single biomarker, with sensitivity = 79%, specificity = 90%, and AUC 0.90. The combined use of PGI/II and anti-PCA resulted in AUC 0.93 for detecting CRAG. Our study suggests that the best combination of non-invasive biomarkers for detecting CRAG is PGI/II with anti-PCA. The addition of G-17 and anti-IFA is of little utility in clinical application.

Objectives Search-and-treat strategy for Helicobacter pylori and surveillance of patients with precancerous lesions are recommended to decrease the burden of gastric cancer in high-risk areas. We aimed to evaluate the acceptance of the target population to these strategies. MethodsWe applied a search-and-treat strategy combined with biomarker screening (pepsinogens I and II, gastrin-17) for atrophic gastritis to healthy individuals aged 40-64 years within the GISTAR Pilot study. Different means of invitation were evaluated -direct telephone calls, letters of invitation via the general practitioners. Participants with altered biomarker results were invited to undergo upper gastrointestinal endoscopy. H.pylori positive individuals were offered eradication therapy. Data on the compliance to the treatment and reasons for noncompliance were collected via telephone. ResultsAltogether 3453 participants were enrolled. The attendance of women participants was 1.9 times higher although active invitation strategies were mainly targeting men. The yield for the telephone invitations was higher than for mail-delivered invitations (2.1 calls vs. 7.7 letters required to recruit one study subject). Out of 661 individuals reached with the invitation to undergo upper endoscopy, 520 (78.7%) attended the procedure. Out of 1185 study subjects eligible for eradication, 810 (68.4%) accepted it. Of those having received the medication, 765(94.4%) completed it. The reasons for nonparticipation were the overall misconception of the importance of screening, busy schedule and others.Conclusions While only the minority of the target population participated in the gastric cancer prevention strategy, relatively high compliance was seen among the participants. The acceptance rate and the identified reasons for refusing to participate in our study indicate that there is a need to raise gastric cancer awareness and its existent preventive strategies within the general population for their successful implementation in the community.