A panel of stomach-specific biomarkers (GastroPanel®) for the diagnosis of atrophic gastritis: A prospective, multicenter study in a low gastric cancer incidence area.

BACKGROUND: Analysis of serum biomarkers for the assessment of atrophic gastritis (AG), considered as gastric precancerous lesion, is of growing interest and recommended by current guidelines. Our aim was to evaluate the diagnostic performance of a panel of biomarkers (GastroPanel®) for the detection of AG in France, a country of a low gastric cancer (GC) incidence. MATERIAL AND METHODS: In this prospective, multicenter, cross-sectional study, consecutive patients considered at increased risk of GC and undergoing upper endoscopy with gastric biopsies were included. Blood samples were collected for the analysis of GastroPanel® (association of Pepsinogens I and II, Gastrin-17, and Helicobacter pylori serology) using ELISA. The results of GastroPanel® were compared to the results of histology considered as the reference. RESULTS: Between 2016 and 2019, 344 patients (148 cases with AG, 196 controls without AG) were included. Sensitivity, specificity, positive, and negative predictive values for the detection of AG by GastroPanel® were of 39.9% (95% CI 31.9; 48.2), 93.4% (95% CI 88.9; 96.4), 81.9 (95% CI 71.1; 90.0), and 67.3 (95% CI 61.4; 72.8), respectively. The sensitivity was significantly higher for the detection of severe AG [60.8% (95% CI 46.1; 74.6) P = .015] and corpus AG [61.0% (95% CI 49.2; 72.0), P = .004]. Diagnostic performances of GastroPanel® tended to be better than those of Pepsinogen I alone, but the difference did not reach statistical significance (P = .068). CONCLUSION: Serum pepsinogen and GastroPanel® tests show promising results for the detection of AG, especially of corpus AG and severe AG, in patients at high risk of GC in France.

Premalignant Gastric Lesions in Patients Included in National Colorectal Cancer Screening.

BACKGROUND: Gastric cancer is the fifth most common malignancy in the world with almost one million new cases annually. Helicobacter pylori infection causes 89% of all gastric cancers. Premalignant lesions (atrophy and intestinal metaplasia) develop after several decades of inflammation. Secondary prevention with gastroscopy is possible, but it is costly and has a low compliance rate. Alternative procedures like serology testing for pepsinogen I and II and pepsinogen I/II ratio are available to select patients for surveillance gastroscopies. PATIENTS AND METHODS: In seven outpatient endoscopic units, 288 patients (154 men; 53.5%), average age 60.68 years, tested positive in National colorectal cancer screening programme SVIT, were included in the study. Gastropanel (BioHit, Finland) was used as a serologic biopsy method. RESULTS: We found 24 patients (12 men, mean age 63.7 years) with pepsinogen (pepsinogen I/II < 3 and/or pepsinogen I < 30 µg/L). Premalignant changes were found on gastric biopsies in 21 patients (7.3% incidence). Operative Link on Gastric Intestinal Metaplasia Assessment (OLGIM) ≥ 1 was found in 20 patients; Operative Link for Gastritis Assessment (OLGA) ≥ 1 was found in 19 patients. Combined accuracy for preneoplastic lesions in Gastropanel positive patients was 87.5%. H. pylori seropositivity was found in 219 patients (76%). Only 24% of our population had normal results. CONCLUSIONS: Gastropanel test has proven to be a reliable non-invasive test for advanced gastric preneoplastic lesions that can select patients for further gastroscopy. We found high H. pylori seropositivity in older age groups in Slovenia.

Accuracy of Serum Biomarker Panel (GastroPanel®) in the Diagnosis of Atrophic Gastritis of the Corpus. Systematic Review and Meta-analysis.

BACKGROUND/AIM: The serological biomarker panel (GastroPanel®)(GP) developed by Biohit Oyj (Helsinki, Finland) has gained increasing global acceptance in the diagnosis of atrophic gastritis (AG). This is a systematic review and meta-analysis of the studies on diagnostic accuracy of GP (GPA). MATERIALS AND METHODS: Core electronic databases were searched until the end of December 2021, following the principles of the PRISMA-P and using the QUADAS-2 quality assessment tool. STATA software with relevant packages (metandi, midas, mylabels) was used for meta-analysis, with AG of the corpus (AGC) as the endpoint. Summary estimates of Se and Sp, LR+ and LR- were calculated using random effect bivariate model (Forest plots), and summary receiver operating characteristic (SROC) curves by hierarchical SROC (HSROC) model. RESULTS: Altogether, 49 studies were found eligible, comprising 22,597 patients examined by the GP test. Significant heterogeneity across the studies was confirmed in Forest plots, HSROC and bivariate boxplot. The pooled Se of GP in diagnosis of AGC was 0.70 (95%CI=0.64-0.76) and pooled Sp was 0.93 (95%CI=0.90-0.95), with AUC=0.900 (95%CI=0.170-1.000) in HSROC. In Fagan's nomogram, positive GP test predicts AGC at population level with the likelihood of 72%. Meta-regression and subgroup meta-analysis disclosed publication year (<2008>) as the only significant source of heterogeneity, geographic origin of the study being of borderline significance. CONCLUSION: These meta-analytical results confirm the accuracy of GastroPanel® test in the diagnosis of AGC, advocating its applicability i) in screening for gastric cancer risk conditions (AG, Helicobacter pylori), as well as ii) in non-invasive diagnosis of dyspeptic patients, and iii) in follow-up of AG-patients.

Non-invasive Screening of Autoimmune Atrophic Gastritis in Asymptomatic Subjects by Serological Biomarker Test (GastroPanel®).

BACKGROUND/AIM: To estimate the prevalence of autoimmune atrophic gastritis (AAG) in the Russian Federation, a systematic screening of asymptomatic healthy adults by non-invasive biomarker testing was conducted. The aim was i) To test the validity of non-invasive serological screening for AAG; ii) to establish the prevalence of AAG among asymptomatic adults. PATIENTS AND METHODS: Altogether, 1,283 asymptomatic, healthy adults (mean age: 38 years) were screened by GastroPanel® test. Those with a biomarker profile indicating AG (n=46) were invited for further examinations; 21 consented to gastroscopy with biopsies classified using the Updated Sydney System and Operative Link to Gastric Atrophy. Blood tests included parietal cell, intrinsic factor and thyroid peroxidase antibodies, and analysis of vitamin B12 and iron. RESULTS: Gastroscopy and biopsies confirmed AG in 20 of the individuals. Parietal cell, intrinsic factor and thyroid peroxidase antibodies were present in five, one and eight individuals, respectively. AAG-associated co-morbidities (iron deficiency and pernicious anemia) were diagnosed in 10 out of 21. The final diagnosis of AAG was made in 15 out of 1,283 subjects (1.2%), of whom four were Helicobacter pylori-positive. When corrected for verification bias (non-attendees in the confirmatory tests; n=25), the adjusted prevalence of AAG was 2.6% (33/1,283). CONCLUSION: AAG prevalence of 2.6% is among the highest reported using non-invasive tests. GastroPanel® is an optimal screening tool, providing the first link in the diagnostic protocol leading to the final diagnosis of this condition. The role of Helicobacter pylori as a trigger of AAG cannot be ruled out.

Value of GastroPanel in the diagnosis of atrophic gastritis.

Analysis of serum biomarkers for the assessment of atrophic gastritis (AG), considered as precursor of the intestinal type of gastric cancer, is of growing interest. The combination of pepsinogen (PG), gastrin-17 (G17) and anti-Helicobacter pylori (H. pylori) antibody serological assays (panel test) is a non-invasive tool for the diagnosis of atrophic gastritis. However, the diagnostic reliability of this test remains uncertain. The aim of our study was to assess the diagnostic performance of the serum panel test (GastroPanel) for the diagnosis of atrophic gastritis. From dyspeptic patients, endoscopic biopsy samples (two from the gastric corpus and two from the antrum) and blood samples were collected. The determination of sPGI, sPGII, sG17 and IgG antibodies to H. pylori (H.p IgG) was performed using an enzyme-linked immunosorbent assay (GastroPanel; Biohit Oyj). Histopathology results were compared with GastroPanel values. Sixty patients were included: 35 (58.3%) females and 25 (41.66%) males; mean age 67.63±9.36 years; 45% H. pylori-positive. A total of 65% of patients had atrophic gastritis. There were no significant differences between the levels of biomarkers and localization of atrophy. The ratio PG1/PG2 was lower in patients with multifocal atrophy; the difference being close to the threshold of statistical significance. In cases of intestinal metaplasia the values of G17, PG1, PG2, H.p IgG were not statistically altered compared to those without intestinal metaplasia; only the ratio PG1/PG2 was lower in intestinal metaplasia; the difference being almost of statistical significance. Our results revealed that, GastroPanel values did not differ depending on the severity of the atrophy. Biomarkers used by GastroPanel do not have enough accuracy for use in the diagnosis of atrophy in the population studied. A low accuracy only for the ratio PG1/PG2 in patients with multifocal atrophy was found. However, our data revealed a correlation in detecting intestinal metaplasia.

Serological Biomarker Panel in Diagnosis of Atrophic Gastritis and Helicobacter pylori Infection in Gastroscopy Referral Patients: Clinical Validation of the New-Generation GastroPanel® Test.

BACKGROUND/AIM: Prompted by the increasing demand of non-invasive diagnostic tools for screening of gastric cancer (GC) risk conditions, i.e., atrophic gastritis (AG) and Helicobacter pylori (Hp) infection, the GastroPanel® test (GP: biomarker panel of PGI, PGII, G-17, Hp IgG ELISA) that was developed in the early 2000's, was recently updated to a new-generation (unified GP) test version. This clinical validation study evaluated the diagnostic accuracy of the new-generation GP test in detection of AG and Hp among gastroscopy referral patients in a University Clinic. PATIENTS AND METHODS: Altogether, 522 patients were enrolled among the patients referred for gastroscopy at the Gastro Center, Oulu University Hospital (OUH). All patients underwent gastroscopy with biopsies classified using the Updated Sydney System (USS), and blood sampling for GP testing. RESULTS: Biopsy-confirmed AG was found in 10.2% (53/511) of the patients. The overall agreement between the GP and the USS classification was 92.4% (95%CI=90.0-94.6%), with the weighted kappa (κw) of 0.861 (95%CI=0.834-0.883). In ROC analysis using moderate/severe AG of the corpus (AGC2+) as the endpoint, AUC=0.952 (95%CI=0.891-1.000) and AUC=0.998 (95%CI=0.996-1.000) for PGI and PGI/PGII, respectively. Hp IgG antibody ELISA detected biopsy-confirmed Hp-infection with AUC=0.993 (95%CI=0.987-0.999). CONCLUSION: The new generation GastroPanel® is a precise test for non-invasive diagnosis of atrophic gastritis and Hp-infection in dyspeptic patients referred for diagnostic gastroscopy.

Serological Biomarker Test (GastroPanel®) in the Diagnosis of Functional Gastric Disorders, Helicobacter pylori and Atrophic Gastritis in Patients Examined for Dyspeptic Symptoms.

BACKGROUND/AIM: The GastroPanel® test (Biohit Oyj) is interpreted by the GastroSoft® application distinguishing eight biomarker profiles, of which five profiles have a morphological equivalent in the Updated Sydney System (USS) classification of gastritis, and 3 others specify functional disorders of the stomach: 1) high acid output, 2) low acid output, and 3) effects of proton pump inhibitor (PPI) medication. This study evaluated the prevalence of these biomarker profiles in dyspeptic patients. PATIENTS AND METHODS: A cross-sectional study was designed to assess the point prevalence of these biomarker profiles in a random sample of 500 subjects derived from our archives of GastroPanel® samples. RESULTS: Reflux symptoms were reported by 35.2% and use of PPI medication by 36.8% of the study subjects. Biomarker profile 2 (high acid output) was the second most common GastroPanel® profile in this cohort; 31.2%, second only (33.6%) to profile 1 (healthy stomach). Hp-infection was detected in 25.0% of the subjects. Profiles related to use of PPI (low acid output, PPI effect) were found in 7.4% of the cases. AG was uncommon, diagnosed in 14 patients only (2.8%). CONCLUSION: These data are derived from the population with the highest frequency of dyspepsia, and the results might have widespread implications in diagnostic and screening practices.

Helicobacter pylori (Hp) IgG ELISA of the New-Generation GastroPanel® Is Highly Accurate in Diagnosis of Hp-Infection in Gastroscopy Referral Patients.

BACKGROUND/AIM: Helicobacter pylori (Hp) infection affects a substantial proportion of the world population and is a major risk factor of gastric cancer (GC). The caveats of common Hp-tests can be evaded by a serological biomarker test (GastroPanel®, Biohit Oyj, Helsinki), the most comprehensive Hp-test on the market. The clinical validation of Helicobacter pylori IgG ELISA of the new-generation GastroPanel® test is reported. The aim of the study is to validate the clinical performance of the Helicobacter pylori IgG ELISA test in diagnosis of biopsy-confirmed Hp-infection in gastroscopy referral patients. PATIENTS AND METHODS: A cohort of 101 patients (mean age=50.1 years) referred for gastroscopy at the outpatient Department of Gastroenterology (SM Clinic, St. Petersburg) were examined by two test versions to validate the new-generation GastroPanel®. All patients were examined by gastroscopy and biopsies, which were stained with Giemsa for specific identification of Hp in the antrum (A) and corpus (C). RESULTS: Biopsy-confirmed Hp-infection was found in 64% of patients, most often confined to antrum. The overall agreement between Hp IgG ELISA and gastric biopsies in Hp-detection was 91% (95%CI=84.1-95.8%). Hp IgG ELISA diagnosed biopsy-confirmed Hp (A&C) with sensitivity (SE) of 92.3%, specificity (SP) of 88.6%, positive predictive value (PPV) of 93.8% and negative predictive value (NPV) of 86.1%, with AUC=0.904 (95%CI=0.842-0.967). In ROC analysis for Hp detection (A&C), Hp IgG ELISA shows AUC=0.978 (95%CI=0.956-1.000). CONCLUSION: The Hp IgG ELISA test successfully concludes the clinical validation process of the new-generation GastroPanel® test, which retains the unrivalled diagnostic performance of all its four biomarkers, extensively documented for the first-generation test in different clinical settings.

GastroPanel® Biomarker Assay: The Most Comprehensive Test for Helicobacter pylori Infection and Its Clinical Sequelae. A Critical Review.

BACKGROUND/AIM: Several clinical conditions seriously hamper the diagnostic accuracy of the commonly used tests for Helicobacter pylori (Hp), 13C-urea breath test (UBT) and stool antigen test (SAT). The present communication is a critical review of the potential limitations of UBT and SAT, and describes the approach on how these can be avoided. Drawbacks of the Hp tests: False-negative results are most often due to low bacterial load in the stomach due to: i) use of proton pump inhibitor medication; ii) use of antibiotics; iii) presence of atrophic gastritis and hypoacid stomach; iv); bleeding peptic ulcer; v) gastric cancer (GC) and vi) mucosal-associated lymphatic tissue lymphoma. The UBT also gives false-positive results when urease-producing bacterial species, other than Hp colonize an acid-free stomach. Importantly, neither UBT nor SAT are capable of diagnosing atrophic gastritis, thus missing the patients at highest risk for GC. GastroPanel® (Biohit Oyj, Finland) circumvents these shortcomings with a serological test consisting of a panel of stomach-specific biomarkers: pepsinogen I, pepsinogen II, gastrin-17 and Hp antibodies. GastroPanel® is a tool for non-invasive examination of i) dyspeptic patients for exclusion or diagnosis of Hp or atrophic gastritis, also disclosing the status of gastric acid output; ii) for screening of asymptomatic individuals at risk of GC; and iii) for comprehensive diagnosis of Hp infection. GastroSoft® application integrates the biomarker profile with the patient's medical information, accurately classifying the biomarker profiles into eight diagnostic categories. CONCLUSION: Given that Hp is the single most important risk factor of GC, the non-invasive diagnosis and screening of Hp should be based on more accurate and more comprehensive testing than UBT or SAT alone. The GastroPanel® is such test, being completely devoid of the known serious shortcomings of UBT and SAT.

Serological biomarker testing helps avoiding unnecessary endoscopies in obese patients before bariatric surgery.

BACKGROUND: To assess the value of serological biomarker testing as a substitute for esophagogastroduodenoscopy (EGDS) in pre-operative assessment of patients referred for bariatric surgery. METHODS: Sixty-five obese patients with a mean age of 43 years (range: 21-65) and a mean body mass index (BMI) of 44 (range: 36-59) were studied. The patients were tested with a four-biomarker panel: pepsinogen I and II, gastrin-17 (basal and stimulated), and Helicobacter pylori (HP) antibodies (GastroPanel®, Biohit Oyj, Finland). On the basis of the biomarker test, the patients were classified into the HS (healthy stomach) group (n = 22) with the normal biomarker profile and the NHS (non-healthy stomach) group (n = 43). The classification of patients into HS and NHS was evaluated against the gold standard, i.e. EGDS with biopsies. RESULTS: The concordance (Cohen's kappa) between the biomarker test and gastric histology was 0.68; 95% CI 0.504-0.854, with an overall agreement of 84.6% (95% CI 73.9-91.4%). In the NHS group, all 43 patients had biopsy-confirmed chronic gastritis: 39 non-atrophic HP-gastritis, 4 atrophic antrum gastritis (AGA) of moderate severity.In the HS group only 6 patients had mild superficial H.pylori negative gastritis. Of the 22 HS subjects with the normal biomarker profile, 20 (31% of all 65) had no complaints either, while the remaining two had reflux symptoms with esophagitis. In the NHS group 10 patients had esophagitis and 8 had also reflux symptoms. CONCLUSIONS: The normal biomarker profile is an excellent surrogate for healthy stomach, implicating that pre-operative EGDS could have been avoided in 31% of our asymptomatic bariatric surgery patients who had the normal biomarker profile.

Prevalence of H. pylori Infection and Atrophic Gastritis in a Population-based Screening with Serum Biomarker Panel (GastroPanel®) in St. Petersburg.

BACKGROUND/AIM: Russian Federation is among the high-incidence countries for gastric cancer (GC), with the incidence being projected to continue increasing. Using a non-invasive blood test with four stomach-specific biomarkers (pepsinogen-I (PG-I) and -II (PG-II), amidated gastrin-17 (G-17) and Helicobacter pylori (HP) IgG antibodies) in a hospital-based screening setting, we aimed to determine the prevalence of GC risk conditions: HP-infection and atrophic gastritis (AG). PATIENTS AND METHODS: A population-derived cohort of 918 asymptomatic subjects (646 women and 272 men) with a mean age of 51.8 years (range=26-83) was examined with the GastroPanel® (GP) test. GP results were verified by gastroscopy and biopsies (the Updated Sydney System (USS) classification for all test-positive AG cases and for random 5% test-negatives (n=263) to correct for the verification bias. RESULTS: Of the 918 subjects, only 199 (21.7%) tested completely normal, while 76.7% (704/918) had HP-infection. Altogether, in 99 subjects (10.8%), GP suggested AG: atrophic gastritis in the antrum (AGA) (n=21), atrophic gastritis in the corpus (AGC) (n=69) or atrophic pangastritis (AGpan) (n=9). The overall concordance between GP and USS classification was 82.5% (217/263) with weighted kappa intra-class correlation coefficient (ICC)=0.875 (95% confidence interval (CI)=0.840-0.901). The sensitivity/specificity balance in receiver operating characteristic (ROC) analysis for PG-I as a marker of moderate/severe AGC (AGC2+) had area under the curve (AUC)=0.895 (95%CI=0.837-0.953). Using the AGC2+ end-point, verification bias-corrected specificity of PGI reached 96.4% (95%CI=94.7-97.9) and that of PGI/PGII ratio 94.6% (95%CI=92.6-96.3), with inevitable erosion in sensitivities. CONCLUSION: While capable of detecting the subjects at risk for GC (HP and/or AG), GP should be the cost-effective means to break the current ominous trend in GC incidence in Russian Federation.

A Panel of Serum Biomarkers (GastroPanel®) in Non-invasive Diagnosis of Atrophic Gastritis. Systematic Review and Meta-analysis.

BACKGROUND/AIM: To meet the increasing demand of non-invasive tests for screening of gastric cancer (GC) risk, biomarker panel (GastroPanel®) (GP) was designed by Biohit Oyj as the first serological test for stomach health. The aim of the present study was to perform a systematic review and meta-analysis of all studies on GP in diagnosis of atrophic gastritis (AG). MATERIALS AND METHODS: Studies were eligible, if i) GP was used to diagnose biopsy-confirmed AG of the corpus (AGC) and/or antrum (AGA) and ii) exact numbers were available to enable calculating sensitivity (SE) and specificity (SP). Comprehensive Meta-Analysis software was used with maximum likelihood meta-regression (R2 analog). Effect size estimates (SE; SP, 95% confidence interval (CI)) were tested for homogeneity with Cochran's Q and I2 statistics. Potential publication bias was estimated by funnel plot statistics. RESULTS: Altogether, 27 studies were eligible comprising of 8,654 patients from different geographic regions. Significant heterogeneity between studies reporting AGC (n=27) or AGA (n=13) warranted random effects (RE) model for summary statistics. GP performs better in diagnosing AGC than AGA with 70.2% vs. 51.6% pooled SE and 93.9% vs. 84.1% pooled SP, respectively. Limited number of studies erodes the Q test's power to detect true heterogeneity in meta-analysis stratified by geographic study origin. Few hypothetical missing studies had only marginal effect on pooled estimates of SE and SP. CONCLUSION: This first meta-analysis of GP literature corroborates the statement of international experts, advocating GP in diagnosis and screening of AG. Due to its high specificity for both AGA and AGC, GastroPanel® is truly a test for stomach health.

Stomach-specific Biomarkers (GastroPanel) Can Predict the Development of Gastric Cancer in a Caucasian Population: A Longitudinal Nested Case-Control Study in Siberia.

BACKGROUND/AIM: Atrophic gastritis (AG) is the most important risk condition for gastric cancer (GC). A panel of stomach-specific serum biomarkers: pepsinogen (PG) I, pepsinogen (PG) II, gastrin-17 (G-17), and IgG antibodies to H. pylori (HP-Ab) detects the extent and grade of AG. The aim of the present study was to assess the predictive value of this 4-biomarker panel (GastroPanel, Biohit Oyj, Helsinki, Finland) in a case-control setting nested within a cohort of Caucasian population in Western Siberia. PATIENTS AND METHODS: Both the cases and controls for the study derived from a population-based cohort of 45-69-year-old subjects (n=9,360) in the HAPIEE (Health, Alcohol and Psychosocial Factors In Eastern Europe) study, enrolled in Novosibirsk, Siberia during 2003-2005. Cases represent all GCs reported to the Cancer Registry until 2012, being matched (1:2) with healthy controls (COs). Altogether 156 (52 GCs and 104 COs) serum samples collected at study entry were available for GastroPanel analysis. Conditional logistic regression models (uni- and multivariate) were used to analyze this matched case-control setting. RESULTS: The biomarker levels below cut-off at baseline predicted the development of GC as follows: PGI (OR=2.9; 95%CI=1.3-6.4), PGII (OR=9.0; 95%CI=1.8-44.3), PGI/PGII (OR=3.3; 95%CI=1.5-7.3); G-17 (OR=1.8; 95%CI=0.7-4.8), and HP-Ab (OR=0.4; 95%CI=0.1-1.3). In the multivariate model adjusted for sex, age, and all GastroPanel markers, PGI/PGII ratio was the most powerful independent predictor of GC (OR=2.9; 95% CI=1.01-8.0). CONCLUSION: For the first time in a Caucasian population, we demonstrated that PGI, PGII and PGI/PGII ratio are reliable longitudinal predictors of incidence of GC.