Assessment of Serum Pepsinogens with and without Co-Testing with Gastrin-17 in Gastric Cancer Risk Assessment-Results from the GISTAR Pilot Study.

Introduction−−Serum pepsinogen tests for gastric cancer screening have been debated for decades. We assessed the performance of two pepsinogen assays with or without gastrin-17 for the detection of different precancerous lesions alone or as a composite endpoint in a Latvian cohort. Methods−−Within the intervention arm of the GISTAR population-based study, participants with abnormal pepsinogen values by ELISA or latex-agglutination tests, or abnormal gastrin-17 by ELISA and a subset of subjects with all normal biomarker values were referred for upper endoscopy with biopsies. Performance of biomarkers, corrected by verification bias, to detect five composite outcomes based on atrophy, intestinal metaplasia, dysplasia or cancer was explored. Results−−Data from 1045 subjects were analysed, of those 273 with normal biomarker results. Both pepsinogen assays showed high specificity (>93%) but poor sensitivity (range: 18.4−31.1%) that slightly improved when lesions were restricted to corpus location (40.5%) but decreased when dysplasia and prevalent cancer cases were included (23.8%). Adding gastrin-17 detection, sensitivity reached 33−45% while specificity decreased (range: 61.1−62%) and referral rate for upper endoscopy increased to 38.6%. Conclusions−−Low sensitivity of pepsinogen assays is a limiting factor for their use in population-based primary gastric cancer screening, however their high specificity could be useful for triage.

Factors Associated with False Negative Results in Serum Pepsinogen Testing for Precancerous Gastric Lesions in a European Population in the GISTAR Study.

The accuracy of plasma pepsinogen (Pg) as a marker for precancerous gastric lesions (PGL) has shown variable results. We aimed to identify factors associated with false negative (FN) cases in Pg testing and to adjust cut-off values for these factors in order to improve Pg yield. Plasma Pg was measured and upper endoscopy with biopsy was performed within the "Multicentric randomized study of Helicobacter pylori eradication and pepsinogen testing for prevention of gastric cancer mortality: the GISTAR study". A multivariable logistic model was built for FN and multiple factors. Values of Pg were compared and sensitivity and specificity were calculated using pre-existing Pg cut-offs for factors showing strong associations with FN. New cut-offs were calculated for factors that showed substantially lower sensitivity. Of 1210 participants, 364 (30.1%) had histologically confirmed PGL, of which 160 (44.0%) were FN. Current smokers, men, and H. pylori positives were more likely FN. Smoking in H. pylori negatives was associated with a higher Pg I/II ratio and substantially lower sensitivity of Pg testing than in other groups. Adjusting Pg cut-offs for current smokers by H. pylori presence improved sensitivity for detecting PGL in this group. Our study suggests that adjusting Pg cut-offs for current smokers by H. pylori status could improve Pg test performance.

Free-breathing dynamic T1WI using compressed sensing-golden angle radial sparse parallel imaging for liver MRI in patients with limited breath-holding capability.

PURPOSE: Evaluating the performance of free-breathing dynamic T1-weighted imaging (T1WI) using compressed sensing golden-angle radial sparse parallel imaging (CS-GRASP) in non-cooperative patients compared with a general group. METHOD: This retrospective study included patients who underwent gadoxetic acid-enhanced liver MRI using CS-GRASP at 3 T between March 2018 and October 2019. Patients were divided chronologically, into one of two groups: Group 1, who underwent MRI during the sequence implementation period regardless of breath-hold capability; and Group 2, who underwent MRI from June 2018 due to limited breath-hold capability. Three radiologists evaluated motion and streak artifacts as well as overall image quality on a four-point scale at the precontrast phase, late arterial phase (LAP) and portal venous phase (PVP). Intra-individual comparisons were made between sequences in each group. RESULTS: We identified 102 patients, who were divided into either Group 1 (n = 41) or 2 (n = 61). For the LAP, the former group had higher image quality (3.22 ± 0.65 vs. 2.95 ± 0.61, P < 0.001) and less streak artifact (2.96 ± 0.56 vs. 2.74 ± 0.57, P = 0.001) than the latter. However, there was no significant difference between the two groups regarding either the proportion of patients with acceptable motion artifact, at 92.7% (38/41) for Group 1 vs. 96.7% (59/61) for Group 2, or that of patients with acceptable image quality at 80.5% (33/41) for Group 1 vs. 65.6% (40/61) for Group 2 (P > 0.05). In intra-individual comparisons, portal phase showed the highest image quality than the others in both groups (P < 0.001). CONCLUSIONS: Acceptable image quality for the LAP in non-cooperative patients was provided with a success rate of over 50% via free-breathing T1WI using CS-GRASP.

Lifestyle and dietary factors associated with serologically detected gastric atrophy in a Caucasian population in the GISTAR study.

OBJECTIVE: To identify dietary and lifestyle factors associated with decreased pepsinogen levels indicative of gastric atrophy. METHODS: Participants aged 40 to 64 from the "Multicentric randomized study of H. pylori eradication and pepsinogen testing for prevention of gastric cancer mortality (GISTAR study)" in Latvia tested for serum pepsinogen, as well as for Helicobacter pylori infection by 13 C-urea breath test or serology were included. Data on sex, age, education, employment, diet, smoking, alcohol and proton pump inhibitor use were obtained by survey and compared for participants with and without serologically detected gastric atrophy defined as pepsinogen I/pepsinogen II ≤ 2 and pepsinogen I ≤ 30 ng/mL. RESULTS: Of 3001 participants (median age 53, interquartile range, 11.0, 36.9% male) 52.8% had H. pylori and 7.7% had serologically detected gastric atrophy. In multivariate analysis, increasing age, consumption of alcohol, coffee, and onions were positively, while H. pylori , former smoking, pickled product and proton pump inhibitor use were inversely associated with gastric atrophy. Pepsinogen values were higher in smokers and those with H. pylori . Pepsinogen ratio was lower in those with H. pylori . When stratifying by H. pylori presence, significantly higher pepsinogen levels remained for smokers without H. pylori . CONCLUSION: Several dietary factors and smoking were associated with serologically detected gastric atrophy. Pepsinogen levels differed by smoking and H. pylori status, which may affect the serologic detection of gastric atrophy. There seems to be a complicated interaction between multiple factors. A prospective study including atrophy determined by both serology and histology is necessary.

Does Family History of Cancer Influence Undergoing Screening and Gastrointestinal Investigations?

BACKGROUND AND AIMS: Although a family history of cancer (FHC) can modify the lifestyle and attitudes towards participation in cancer screening programs, studies on this relationship show mixed results and vary across populations. The objectives of the study were to compare sociodemographic characteristics, history of gastrointestinal (GI) investigations and Helicobacter pylori eradication, and modifiable cancer risk factors between those with FHC and those with no FHC (NFHC), and to investigate the association between FHC and a history of GI investigations. METHODS: A total of 3,455 questionnaires from the pilot study of the "Helicobacter pylori eradication and pepsinogen testing for prevention of gastric cancer mortality (GISTAR study)" in Latvia were analysed. We compared sociodemographic characteristics and history of GI investigations between participants with self- reported FHC and NFHC. Binary logistic regression models adjusted for socio-demographic characteristics and modifiable cancer risk factors were built for a FHC and each GI investigation. RESULTS: Participants with a FHC were more likely to be women, have a higher education and less likely to have harmful habits (smoking, alcohol consumption) than those with NFHC. Participants with a FHC were approximately twice as likely to report recent colorectal investigations specifically for screening, than those with NFHC. In fully adjusted logistic regression models, FHC was significantly associated with a recent history of faecal occult blood tests (FOBTs), colonoscopies, and colorectal investigations (FOBT or colonoscopy) specifically for screening as part of the national organized screening programme. CONCLUSION: Our results indicate that those with a FHC have different patterns of health-related behaviour than those with NFHC.

Sociodemographic, Lifestyle and Medical Factors Associated with Helicobacter Pylori Infection.

BACKGROUND AND AIMS: The prevalence of Helicobacter pylori (H. pylori) infection is higher in developing countries and is often linked to lower socioeconomic status. Few studies have investigated the association between H. pylori and individual level characteristics in Europe, where several countries have a high prevalence of H. pylori infection. The study aimed to identify risk factors for H. pylori infection among adults in a large clinical trial in Latvia. METHODS: 1,855 participants (40-64 years) of the "Multicenter randomized study of H. pylori eradication and pepsinogen testing for prevention of gastric cancer mortality" (GISTAR study) in Latvia tested for H. pylori IgG antibodies were included in a cross-sectional analysis. Sociodemographic, lifestyle and medical factors were compared for participants seropositive (H. pylori+) and seronegative. Mutually adjusted odds ratios (OR) were calculated for H. pylori+ and factors significant in univariate analysis (education, smoking, binge drinking, several dietary habits, history of H. pylori eradication and disease), adjusting for age, gender and income. RESULTS: Of the participants 1,044 (55.4%) were H. pylori seropositive. The infection was associated with current (OR: 1.34, 95%CI: 1.01-1.78) and former (OR: 1.38; 95%CI: 1.03-1.85) smoking, binge drinking (OR: 1.35; 95%CI: 1.03-1.78), having ≥200g dairy daily (OR: 1.37; 95%CI: 1.11-1.69), and very hot food/drinks (OR: 1.32; 95%CI: 1.03-1.69) and inversely with ≥400g vegetables/fruit daily (OR: 0.76; 95%CI: 0.60-0.96), history of H. pylori eradication (OR: 0.57; 95%CI: 0.39-0.84), peptic ulcer (OR: 0.55; 95%CI: 0.38-0.80) and cardiovascular disease (OR: 0.78; 95%CI: 0.61-0.99). CONCLUSIONS: After mutual adjustment, H. pylori seropositivity was associated with lifestyle and in particular dietary factors rather than socioeconomic indicators in contrast to the majority of other studies.