Comparison between the GastroPanel test and the serum pepsinogen assay interpreted with the ABC method-A prospective study.

BACKGROUND AND AIMS: This study aimed to validate Helicobacter pylori serological and pepsinogen (PG) assays for detecting infection and gastric neoplasm. METHODS: Individuals who underwent serum Chorus H. pylori and HBI PG assays were included from May to September 2023. The GastroPanel test was performed using the same blood sample. HBI assay findings were interpreted with the ABC method using the criteria of corpus atrophy (PG I ≤ 70 ng/mL & I/II ≤3) and advanced corpus atrophy (PG I ≤ 30 ng/mL & I/II ≤2). RESULTS: A total of 144 H. pylori-infected and 184 non-infected Koreans were analyzed. The Chorus test (sensitivity 97.2%, specificity 89.1%) showed higher area under the curve (0.993 vs. 0.972, p = 0.003) than the GastroPanel test (sensitivity 95.8%, specificity 86.4%). Using the GastroSoft application, the incidence of gastric neoplasms was highest in the corpus atrophy group (50%), followed by the low acid-output (25.8%), H. pylori infection (11.6%), and antral atrophy (9.1%) groups. There were no gastric neoplasms in the normal and high acid output groups. Using the ABC method, the incidence of gastric neoplasms was highest in the corpus atrophy groups (23.8% in Groups C and D), followed by Group B (12.3%) and Group A (2.4%). Corpus atrophy interpreted with the GastroSoft showed poor agreement (k = 0.225) with corpus atrophy interpreted with the ABC method, whereas it showed excellent agreement (k = 0.854) with advanced corpus atrophy. CONCLUSIONS: Although the Chorus test was more accurate than the GastroPanel test, both assays discriminated high-risk individuals by detecting atrophy or infection. There were no gastric neoplasms in the normal or high acid-output groups (GastroSoft application), and gastric neoplasm incidence was lowest in Group A (ABC method). Corpus atrophy determined by GastroSoft application is more consistent with advanced corpus atrophy determined by the ABC method than is corpus atrophy.

Randomized controlled trial comparing the costs of gastric cancer screening systems between serological risk-based upper gastrointestinal endoscopy and the existing barium photofluorography: gastric cancer screening labeled by serum examination in place of aged gastric cancer organized screening systems (GALAPAGOS study).

BACKGROUND: Although the risk of gastric cancer can be stratified according to Helicobacter pylori (H. pylori) IgG antibody titer and pepsinogen levels (ABC classification), a population-based gastric cancer screening system combining serological tests and endoscopy has not been introduced. This study aimed to compare the total testing cost per participant between the ABC classification method and the existing protocol. METHODS: Using the minimization method with sex and age as allocation factors, 1206 participants were randomly assigned to the following two methods for a 5-year intervention: barium photofluorography as primary examination followed by detailed examination with upper gastrointestinal endoscopy (Ba-Endo) and risk-based upper gastrointestinal endoscopy by ABC classification (ABC-Endo). The primary endpoint was the total testing cost per participant over a 5-year period. The secondary endpoint was the expense required to detect one gastric cancer. RESULTS: The total testing cost per participant was 39,711 yen in Ba-Endo (604 participants) and 45,227 yen in ABC-Endo (602 participants), with the latter being significantly higher (p < 0.001). During the intervention period, gastric cancer was found in 11 and eight participants in Ba-Endo and ABC-Endo, respectively. The expenses required to detect one gastric cancer were 2,240,931 yen in Ba-Endo and 3,486,662 yen in ABC-Endo. CONCLUSIONS: The testing cost per participant turned out to be higher in the ABC-Endo group than in the Ba-Endo group. This superiority trial, based on the hypothesis that the cost of testing is lower for ABC-Endo than for Ba-Endo, was rejected.

B12 deficiency-related glossitis is highly associated with high gastrin-17 and low pepsinogen I.

BACKGROUND: The causes of vitamin B12 (B12) deficiency are varied and mainly related to gastric disorders. Glossitis is a common oral manifestation of B12 deficiency and is often first seen by dentists. This study aimed to investigate the correlation between B12 deficiency-related glossitis (B12-def glossitis) and gastric serum biomarkers [gastrin-17(G17), pepsinogen I (PGI), pepsinogen II (PGII), and anti-Helicobacter pylori (H. pylori) antibodies], and preliminarily discuss the etiology of B12-def glossitis. METHODS: A cross-sectional study was conducted in patients complaining of glossodynia, burning sensation, or severe recurrent oral ulcers, but patients with a history of gastrectomy were excluded. All subjects underwent a uniform oral examination and hematological tests. RESULTS: Of 243 patients, 133 with B12-def glossitis were in the case group, and 110 with other oral mucosal diseases (non-glossitis) and normal B12 levels were in the control group. In the case group, 84.2% (112/133) showed high G17 and low PGI levels (G17hi PGIlow ). Univariate logistic regression showed that G17hi PGIlow was a high-risk factor for B12-def glossitis (OR: 92.44; 95% CI: 35.91, 238.02). Subgroup analyses in the case group showed that the G17hi PGIlow group presented with lower B12 levels and a lower positive rate of anti-H. pylori antibodies compared to the non-G17hi PGIlow group. CONCLUSION: Gastric serum biomarkers in patients with B12-def glossitis generally showed G17hi PGIlow , suggesting possible atrophy of gastric corpus and fundus mucosa. The G17hi PGIlow and non-G17hi PGIlow groups may represent different etiologies of B12 deficiency.

Development of a modified ABC method among Helicobacter pylori infected but serum pepsinogen test-negative individuals.

BACKGROUND: Although the ABC method for gastric cancer (GC) screening has been widely adopted in Japan, it may not be suitable for other countries due to population heterogeneity and different tumor histology. We aim to develop a modified ABC method to improve GC screening performance, especially among Helicobacter pylori (Hp) infected but serum pepsinogen (sPG) test-negative individuals. METHODS: A total of 4745 participants were recruited from Tianjin, China, and were classified into four groups by combined assay for Hp infection and sPG concentrations: Group A (Hp [-], PG [-]), Group B (Hp [+], PG [-]), Group C (Hp [+], PG [+]), and Group D (Hp [-], PG [+]). We used receiver-operating characteristic (ROC) curves analysis and minimum p value method to determine the optimal cutoff point for PG II in Group B. We performed logistic regressions to examine the risk of GC across different subgroups. In addition to the derivation set, the performance of the modified ABC method was also evaluated in an external set involving 16,292 participants from Liaoning, China. RESULTS: In the modified ABC method, we further classified Group B as low-risk (Group B1) and high-risk subgroups (Group B2) using optimal sPG II cutoff point (20.0 ng/mL) by ROC curves analysis and minimum p value method. Compared with Group B1, Group B2 had a significantly higher risk of GC (adjusted OR = 2.54, 95% CI = 1.94-3.33). The modified ABC method showed good discrimination for GC (AUC = 0.61, 95% CI = 0.59-0.63) and improved risk reclassification (NRI = 0.11, p < .01). Similar results were observed in the validation dataset. CONCLUSIONS: The modified ABC method can effectively identify high-risk population for GC among Hp-infected but sPG test-negative participants in China.

Development and validation of LightGBM algorithm for optimizing of Helicobacter pylori antibody during the minimum living guarantee crowd based gastric cancer screening program in Taizhou, China.

Gastric cancer continues to be a significant health concern in China, with a high incidence rate. To mitigate its impact, early detection and treatment is key. However, conducting large-scale endoscopic gastric cancer screening is not feasible in China. Instead, a more appropriate approach would be to initially screen high-risk groups and follow up with endoscopic testing as needed. We conducted a study on 25,622 asymptomatic participants aged 45-70 years from a free gastric cancer screening program in the Taizhou city government's Minimum Living Guarantee Crowd (MLGC) initiative. Participants completed questionnaires, blood tests, and underwent gastrin-17 (G-17), pepsinogen I and II (PGI and PGII), and H. pylori IgG antibody (IgG) assessments. Using the light gradient boosting machine (lightGBM) algorithm, we developed a predictive model for gastric cancer risk. In the full model, F1 score was 2.66%, precision was 1.36%, and recall was 58.14%. In the high-risk model, F1 score was 2.51%, precision was 1.27%, and recall was 94.55%. Excluding IgG, the F1 score was 2.73%, precision was 1.40%, and recall was 68.62%. We conclude that H. pylori IgG appears to be able to be excluded from the prediction model without significantly affecting its performance, which is important from a health economic point of view. It suggests that screening indicators can be optimized, and expenditures reduced. These findings can have important implications for policymakers, as we can focus resources on other important aspects of gastric cancer prevention and control.

The application of new gastric cancer screening score system for gastric cancer screening and risk assessment of gastric precancerous lesions in China.

Objective: To evaluate the value of new gastric cancer screening score system for risk assessment of gastric precancerous lesions.Methods: A total of 520 patients were enrolled after the examination of endoscopy at Endoscopy Center, Department of Gastroenterology, from June 2018 to December 2021. The patients were divided into three groups according to age, gender, serum helicobacter pylori antibody test, pepsinogen I (PGI), pepsinogen II (PGII), pepsinogen I/II ratio (PGR) and gastrin-17 test results before endoscopy: Group A defined as low-risk group (0-11 points), Group B defined as middle-risk group (12-16 points), Group C defined as high-risk group (17-23 points). The detection rates of gastric cancer and atrophic gastritis in three groups were analyzed. According to the range and degree of atrophy/intestinal metaplasia, patients were divided into five groups on the basis of OLGA/OLGIM staging system. The levels of PG I, PG II and PGR were compared between different groups, and the correlation between new gastric cancer screening score system and OLGA/OLGIM staging system were evaluated. Statistical analysis was accomplished by ANOVA, chi-square test and Gamma coefficient analysis.Results: A total of 520 patients were enrolled. 268 patients were classified into group A,222 patients into group B and 30 patients into group C, respectively. According to the pathological results, 281 cases were non-atrophic gastritis, 230 cases atrophic gastritis and 9 cases gastric cancer. For OLGA staging system, 281 patients were divided into stage-0 group, 121 patients into stage-I group, 72 patients into stage-II group, 33 patients into stage-III group and 13 patients into stage-IV groups. The PGI and PGR level correlated inversely with the rising OLGA stages (F = 3.028, p = .016, F = 6.036, p < .001). For OLGIM staging system, 252 patients were divided into stage-0 group, 137 patients into stage-I group, 80 patients into stage-II group, 36 patients into stage-III group and 15 patients into stage-IV group. The PGR level correlated inversely with the rising OLGIM stages (F = 3.466, p＝.007). The detection rates of gastric cancer and atrophic gastritis in Group C were much higher than other groups. (X2 = 14.727, p < .001; X2 = 51.280, p < .001). Gamma coefficient analysis showed significant correlations between OLGA/OLGIM and the new gastric cancer screening score system (p < .001).Conclusions: The new gastric cancer screening score system is closely linked with histological OLGA/OLGIM staging system in the risk assessment of gastric precancerous lesions. The role of new gastric cancer screening score system in future gastric precancerous lesions screening and high risk population identifying was promising.

Diagnostic performance of the normal range of gastrin calculated using strict criteria based on a combination of serum markers and pathological evaluation for detecting gastritis: a retrospective study.

BACKGROUND: The ABC method, which combines the pepsinogen method and anti-Helicobacter pylori antibody titers, has been used for risk screening for gastric cancer in Japan. However, it has been reported that there are cases of gastritis and carcinogenesis risk even in group A, which is considered to be a low-risk group based on the ABC method. Currently, in group A, endoscopic examination is needed to strictly discriminate "patients without gastritis" (defined as true A patients) from those "with gastritis." A simple and minimally invasive diagnostic criterion for gastritis using serological markers is desirable. In this study, we aimed to identify the normal serum gastrin concentrations in normal stomach cases based on pathological diagnosis and investigate the usefulness of serum gastrin concentrations in diagnosing gastritis. METHODS: Patients who underwent endoscopy and blood tests at Hiroshima University Hospital were enrolled in the study and categorized into the "pathologically-evaluated group" and "endoscopically-evaluated group," according to the evaluation method of atrophic gastritis. Initially, we measured serum gastrin concentrations in the normal stomach cases in the pathologically-evaluated group and calculated the normal range of serum gastrin concentrations. We used the upper limit of this normal range of serum gastrin concentrations and performed a validation study to determine its usefulness as a diagnostic marker for distinguishing between cases of gastritis and true A in the endoscopically-evaluated group. RESULTS: The 95th percentile of serum gastrin concentrations in pathologically-evaluated normal stomach cases was 34.12-126.03 pg/mL. Using the upper limit of this normal range of serum gastrin concentrations, the sensitivity, specificity, positive predictive value, and negative predictive value for gastritis were 52.8%, 92.6%, 97.0%, and 31.0%, respectively. Additionally, the receiver operating characteristic (ROC) curve for the endoscopically-evaluated group showed an area under the ROC curve of 0.80. CONCLUSION: The gastrin cut-off value of 126 pg/mL has a good positive predictive value (97.0%) for detecting gastritis positing its use as a marker for cases requiring endoscopy. However, the identification of patients with gastritis having normal serum gastrin concentrations due to insufficient sensitivity remains a challenge for the future.

Sex-specific disparities of serum pepsinogen I in relation to body mass index.

OBJECTIVES: The clinical significance of serum pepsinogen (PG) for screening gastric cancer has been a controversial topic. Serum PG I levels have been demonstrated to be correlated with age, sex, and the Helicobacter pylori (HP) infection. However, the underlying factors that influence serum PG I variations remain to be fully elucidated. We aimed to evaluate the impacts of sex and body mass index (BMI) on PG I in Chinese population. METHODS: The cross-sectional study recruited 4,299 apparently healthy participants in Fujian Province. Serum PG levels were automatically measured using ELISA method. Serum H. pylori-IgG antibody was detected by the colloidal gold immunoassay. Clinical characteristics were obtained by questionnaire. RESULTS: Totally, 2,263 participants who had tests of serum PG and anti-HP IgG antibody were enrolled. Increased BMI and serum uric acid were observed in males with low PG I value (<70 µg/L). Multiple logistic regression showed the presence of overweight was the independent risk factor for male participants with low PG I level (odds ratio [OR] 1.519; p=0.017). However, the association was not found in females. CONCLUSIONS: Sex-specific association of serum low PG I with overweight was observed in the southeast coastal areas of China. Thus, effects of sexual dimorphism should not be ignored during the clinical utilization of serum PG I.

Pepsinogen ratio and brachial-ankle pulse wave velocity: a cross-sectional study on their interrelationship in atherosclerosis.

BACKGROUND: Existing research has established the pepsinogen ratio (PGR) as a complex biomarker, not only as an independent predictor for various gastrointestinal diseases but also in its association with atherosclerotic cardiovascular diseases. However, the precise mechanism linking changes in PGR to cardiovascular pathologies remains unclear. The objective of this study is to quantitatively elucidate the association between PGR and brachial-ankle pulse wave velocity (baPWV) as an indicator of atherosclerotic progression. METHODS: We conducted a cross-sectional study that analyzed clinical data from 465 patients who underwent health screenings. One-way Analysis of Variance (ANOVA) identified potential risk factors affecting baPWV. Multiple logistic regression was employed to evaluate if PGR serves as an independent risk factor for elevated baPWV after accounting for these variables. Generalized additive models and smoothed curve fitting were utilized to investigate the possibility of a nonlinear association between PGR and baPWV. When such nonlinearity was found, threshold effect analysis pinpointed the inflection point in this relationship, followed by segmented correlation analyses. RESULTS: PGR negatively correlated with both right baPWV (RbaPWV) and left baPWV (LbaPWV) after adjusting for confounders. Smoothed curve analyses revealed nonlinear relationships, with inflection points at 22.5 for RbaPWV and 22.3 for LbaPWV. For PGR values below 22.5, a significant negative correlation with RbaPWV was observed (ß = - 6.3 cm/s, P < 0.001). Conversely, for PGR values above 22.5, no significant linear relationship was found (P = 0.141). Similarly, when PGR was below 22.3, a strong negative correlation with LbaPWV was detected (ß = - 7.0 cm/s, P < 0.001), but such correlation was absent for higher PGR levels (P = 0.273). CONCLUSION: The study reveals that PGR is associated with RbaPWV and LbaPWV in a nonlinear manner. Specifically, lower levels of PGR were linearly and inversely correlated with baPWV, but this relationship became nonlinear at higher PGR levels. These findings suggest that modulating PGR levels may offer a therapeutic strategy for managing atherosclerosis.

Appropriateness of Proton Pump Inhibitor Prescription Evaluated by Using Serological Markers.

Inappropriate prescription of proton pump inhibitors (PPI) has been widely reported, often lacking initial exclusion of Helicobacter pylori (HP) infection and evaluation of gastric functional status. The aim of this study was to evaluate the utility of gastric functional tests to define the acid output, as well as HP status, in order to better direct PPI therapy prescription. Dyspeptic patients without alarm symptoms from a primary care population were evaluated. For each patient, serum Pepsinogen I (PGI) and II (PGII), gastrin 17 (G17) and anti-HP IgG antibodies (Biohit, Oyj, Finland) were determined. For each subject, data were collected regarding symptoms, past medical history of HP infection, and PPI use. Therapeutic response to PPIs was determined according to PGI and G17 values, where G17 > 7 in the presence of elevated PGI and absence of chronic atrophic gastritis (CAG) was considered an adequate response. Among 2583 dyspeptic patients, 1015/2583 (39.3%) were on PPI therapy for at least 3 months before serum sampling, and were therefore included in the study. Active HP infection and CAG were diagnosed in 206 (20.2%) and 37 (3.6%) patients, respectively. Overall, an adequate therapeutic response to PPIs was observed in 34.9%, reaching 66.7% at the highest dose. However, 41.1% and 20.4% of patients showed low (G17 1-7) or absent (G17 < 1) response to PPI, regardless of the dosage used. According to gastric functional response, most patients currently on PPI maintenance therapy lack a proper indication for continuing this medication, either because acid output is absent (as in CAG) or because gastrin levels fail to rise, indicating absence of gastric acid negative feedback. Lastly, HP eradication is warranted in all patients, and gastric function testing ensures this pathogen is sought for and adequately treated prior to initiating long-term PPI therapy.

A DSC Test for the Early Detection of Neoplastic Gastric Lesions in a Medium-Risk Gastric Cancer Area.

In this study, we aimed to assess the accuracy of the proposed novel, noninvasive serum DSC test in predicting the risk of gastric cancer before the use of upper endoscopy. To validate the DSC test, we enrolled two series of individuals living in Veneto and Friuli-Venezia Giulia, Italy (n = 53 and n = 113, respectively), who were referred for an endoscopy. The classification used for the DSC test to predict gastric cancer risk combines the coefficient of the patient's age and sex and serum pepsinogen I and II, gastrin 17, and anti-Helicobacter pylori immunoglobulin G concentrations in two equations: Y1 and Y2. The coefficient of variables and the Y1 and Y2 cutoff points (>0.385 and >0.294, respectively) were extrapolated using regression analysis and an ROC curve analysis of two retrospective datasets (300 cases for the Y1 equation and 200 cases for the Y2 equation). The first dataset included individuals with autoimmune atrophic gastritis and first-degree relatives with gastric cancer; the second dataset included blood donors. Demographic data were collected; serum pepsinogen, gastrin G17, and anti-Helicobacter pylori IgG concentrations were assayed using an automatic Maglumi system. Gastroscopies were performed by gastroenterologists using an Olympus video endoscope with detailed photographic documentation during examinations. Biopsies were taken at five standardized mucosa sites and were assessed by a pathologist for diagnosis. The accuracy of the DSC test in predicting neoplastic gastric lesions was estimated to be 74.657% (65%CI; 67.333% to 81.079%). The DSC test was found to be a useful, noninvasive, and simple approach to predicting gastric cancer risk in a population with a medium risk of developing gastric cancer.

Usefulness of Serum Pepsinogen I as a Biomarker in Early Diagnosis of Aetiology of Dyspepsia.

BACKGROUND: Dyspepsia, according to Rome III criteria, is defined as pain or discomfort centred in the upper abdomen in addition to symptoms like early satiety, postprandial fullness, bloating and nausea. Pepsinogens which are secreted by chief cells of the stomach play an important role in its physiology. They could determine the functional state of the mucosa in health and in diseased conditions. Serum levels of pepsinogen have aided the diagnosis of gastric pathologies such as atrophic gastritis, peptic ulcer disease and gastric cancer. Pepsinogen assay, being a simple, non-invasive procedure, can aid in determining the aetiology of dyspepsia especially in a resource poor setting. OBJECTIVE: This was to evaluate the diagnostic significance of serum pepsinogen I in patients with dyspepsia. METHODS: The study involved 112 adult patients with dyspepsia and an equal number of controls. A questionnaire was used to obtain biodata, clinical features and other relevant information. The patients had abdominal ultrasound scan, urea breath test and upper gastrointestinal endoscopy (UGIE), while the controls had only abdominal ultrasound scan. Sera prepared from 10ml of venous blood from each participant were stored at -20ºC and later analysed for pepsinogen I (PG I). RESULTS: Females predominated in both groups (F:M = 1.4:1). The mean age of cases was 51±15.9 years and was similar to that of controls 51.4±16.5. The most frequent symptom was epigastric pain in 101 (90.2%) patients. Median pepsinogen I level in patients (28.5ng/ml) was significantly lower than in controls (68.8ng/ml) (p<0.001). The most frequent endoscopic finding was gastritis. Serum PG I level at a cut-off point of 79.5ng/ml had a specificity of 88.8% and sensitivity of 40% in identifying dysplasia. CONCLUSION: Serum PG I level was lower in patients with dyspepsia than controls. It showed high specificity in identifying dysplasia and could be a biomarker for early gastric cancer.

CONTEXTE: La dyspepsie, selon les critères de Rome III, est définie comme une douleur ou une gêne centrée sur la partie supérieure de l'abdomen, en plus de symptômes tels qu'une satiété précoce, une plénitude postprandiale, des ballonnements et des nausées. Les pepsinogènes, sécrétés par les cellules principales de l'estomac, jouent un rôle important dans sa physiologie. Ils peuvent déterminer l'état fonctionnel de la muqueuse, qu'elle soit saine ou malade. Les taux sériques de pepsinogène ont facilité le diagnostic de pathologies gastriques telles que la gastrite atrophique, l'ulcère gastroduodénal et le cancer gastrique. Le dosage du pepsinogène, qui est une procédure simple et non invasive, peut aider à déterminer l'étiologie de la dyspepsie, en particulier dans un contexte de ressources limitées. OBJECTIF: Évaluer l'importance diagnostique du pepsinogène I sérique chez les patients souffrant de dyspepsie. MÉTHODES: L'étude a porté sur 112 patients adultes souffrant de dyspepsie : L'étude a porté sur 112 patients adultes souffrant de dyspepsie et un nombre égal de témoins. Un questionnaire a été utilisé pour obtenir les données biologiques, les caractéristiques cliniques et d'autres informations pertinentes. Les patients ont subi une échographie abdominale, un test respiratoire à l'urée et une endoscopie gastro-intestinale supérieure, tandis que les témoins n'ont subi qu'une échographie abdominale. Les sérums préparés à partir de 10 ml de sang veineux de chaque participant ont été conservés à -20ºC et analysés ultérieurement pour le pepsinogène I (PG I). RÉSULTATS: Les femmes prédominaient dans les deux groupes (F:M = 1,4:1). L'âge moyen des cas était de 51±15.9 ans et était similaire à celui des témoins 51.4±16.5. Le symptôme le plus fréquent était la douleur épigastrique chez 101 (90,2 %) patients. Le taux médian de pepsinogène I chez les patients (28,5 ng/ml) était significativement plus bas que chez les témoins (68,8 ng/ml) (p<0,001). Le résultat endoscopique le plus fréquent était la gastrite. Le taux sérique de PG I à un seuil de 79,5 ng/ml avait une spécificité de 88,8 % et une sensibilité de 40 % dans l'identification de la dysplasie. CONCLUSION: Le taux de PG I sérique était plus faible chez les patients souffrant de dyspepsie que chez les témoins. Il a montré une spécificité élevée dans l'identification de la dysplasie et pourrait être un biomarqueur pour le cancer gastrique précoce. Mots-clés: Dyspepsie, Pepsinogène I sérique, Helicobacter pylori, Biomarqueur.

Identification of serologically active Helicobacter pylori antigens related to alterations in serum pepsinogen levels.

Gastric adenocarcinoma is associated with Helicobacter pylori infection. The transition to a carcinogenic process is preceded by glandular atrophy and serum levels of pepsinogen I and II (PGI and PGII) correlate with this type of gastric lesions. Possible associations of serum PG levels in relation to the frequency of serological activity against H. pylori antigens were studied. Serum samples from patients with gastric pathology associated with H. pylori (n=26) and asymptomatic individuals as controls (n=37) were used. Seroactive antigens were identified by immunoblot using a protein extract of H. pylori. The antibody titers anti-H. pylori and the concentration of PGs in serum was determined by ELISA. Thirty-one seroactive antigens were identified, nine of which exhibited a differential frequency between both groups (116.7, 68.8, 61.9, 54.9, 45.6, 38.3, 36.5, 33.8 and 30.1kDa) and only 3 were related to altered levels of PGs in serum. In the control group, the seropositivity of the 33.8kDa antigen was related to an increase in PGII, while the 68.8kDa antigen was related to normal PG values (decreased PGII and elevated PGI/PGII levels) indicating that seropositivity to this antigen could be a protective factor to gastric pathology. The seropositivity of the 54.9kDa antigen was related to altered values of PGs indicative of inflammation and gastric atrophy (increased in PGII and decreased in PGI/PGII). The identification of serum alterations in pepsinogen levels related to seropositivity to H. pylori 33.8, 54.9 and 68.8kDa antigens sets a precedent for further study as possible prognostic serological biomarkers.

[Diagnostic Value of Serum Pepsinogen â /Pepsinogen â ¡ Combined with Tumor Markers for Helicobacter pylori-Positive Early-Stage Gastric Cancer].

Objective: To investigate the diagnostic value of serum pepsinogen (PG) Ⅰ/PGⅡ combined with tumor markers for Helicobacter pylori ( Hp)-positive early-stage gastric cancer. Methods: A retrospective study was conducted with the clinical data of 109 patients with gastric cancer (the gastric cancer group), 115 patients with chronic atrophic gastritis (the benign group), 112 cases of low-grade intraepithelial neoplasia (the low grade group), 109 cases of high-grade intraepithelial neoplasia (the high grade group), and 104 healthy subjects who underwent the relevant screening tests as part of their general physical examination (the healthy group). All the subjects were admitted to or received care at our hospital between May 2018 and April 2021. The levels of serum PGⅠ, PGⅡ, carcinoembryonic antigen (CEA), carbohydrate antigen 199 (CA199), and carbohydrate antigen 724 (CA724), and Hp infection status were examined. The findings for these indicators were compared among the groups, and the differences in serum indicators in Hp-positive and Hp-negative patients were compared. The diagnostic value of serum PGⅠ/PGⅡ combined with tumor markers for Hp-positive early-stage gastric cancer was assessed with receiver operating characteristic (ROC) curve. Results: The serum levels of PGⅠ and PGⅠ/PGⅡ decreased in successive order in the healthy group, the benign group, the low grade group, the high grade group, and the gastric cancer group ( P<0.05). The serum levels of PGⅡ, CEA, CA199, and CA724 in the gastric cancer group, the high grade group, and the low grade group were all higher than those in the healthy group and the benign group ( P<0.05). The Hp-positive rates of the gastric cancer group, the high grade group, the low grade group and the benign group were higher than that of the healthy group ( P<0.01). The levels of serum PGⅠ, PGⅡ, CEA, CA199, and CA724 of the Hp-positive subjects of the healthy group, the benign group, the low grade group, the high grade group, and the gastric cancer group were higher than those of the Hp-negative subjects ( P<0.05), while their PGⅠ/PGⅡ levels were always lower than those of the Hp-negative persons ( P<0.05). The specificity and area under the curve ( AUC) of serum PGⅠ/PGⅡ, CEA, CA199, and CA724 in the combined diagnosis of Hp-positive early-stage gastric cancer were higher than those of each indicator used alone in diagnosis ( P<0.05). In the gastric cancer group, the proportion of patients with PGⅠ/PGⅡ>2.32 was lower in the Hp-positive patients than that in the Hp-negative patients ( P<0.05), while the proportions of patients with CEA>66.99 ng/mL, CA199>110.35 U/mL, and CA724>44.20 U/mL were higher in the Hp-positive patients than those in the Hp-negative patients ( P<0.05). Conclusion: Testing PGⅠ/PGⅡ in combination with CEA, CA199, and CA724 results in better diagnostic value for Hp-positive early-stage gastric cancer.

Activation of dopamine D2 receptor promotes pepsinogen secretion by suppressing somatostatin release from the mouse gastric mucosa.

In vivo administration of dopamine (DA) receptor (DR)-related drugs modulate gastric pepsinogen secretion. However, DRs on gastric pepsinogen-secreting chief cells and DA D2 receptor (D2R) on somatostatin-secreting D cells were subsequently acquired. In this study, we aimed to further investigate the local effect of DA on gastric pepsinogen secretion through DRs expressed on chief cells or potential D2Rs expressed on D cells. To elucidate the modulation of DRs in gastric pepsinogen secretion, immunofluorescence staining, ex vivo incubation of gastric mucosa isolated from normal and D2R-/- mice were conducted, accompanied by measurements of pepsinogen or somatostatin levels using biochemical assays or enzyme-linked immunosorbent assays. D1R, D2R, and D5R-immunoreactivity (IR) were observed on chief cells in mouse gastric mucosa. D2R-IR was widely distributed on D cells from the corpus to the antrum. Ex vivo incubation results showed that DA and the D1-like receptor agonist SKF38393 increased pepsinogen secretion, which was blocked by the D1-like receptor antagonist SCH23390. However, D2-like receptor agonist quinpirole also significantly increased pepsinogen secretion, and D2-like receptor antagonist sulpiride blocked the promotion of DA. Besides, D2-like receptors exerted an inhibitory effect on somatostatin secretion, in contrast to their effect on pepsinogen secretion. Furthermore, D2R-/- mice showed much lower basal pepsinogen secretion but significantly increased somatostatin release and an increased number of D cells in gastric mucosa. Only SKF38393, not quinpirole, increased pepsinogen secretion in D2R-/- mice. DA promotes gastric pepsinogen secretion directly through D1-like receptors on chief cells and indirectly through D2R-mediated suppression of somatostatin release.

Pepsinogens and Gastrin Demonstrate Low Discrimination for Gastric Precancerous Lesions in a Multi-Ethnic United States Cohort.

Early identification of gastric precancerous lesions, including atrophic gastritis (AG) and intestinal metaplasia (IM), may improve gastric cancer detection and prevention. Because AG and IM are generally asymptomatic, many of the estimated 15 million Americans who carry these lesions remain undiagnosed.1 AG and IM are associated with either active or prior Helicobacter pylori (Hp) infection. Hp infection leads to perturbations in the serum concentration of gastric hormones pepsinogen I (PGI), pepsinogen II, the pepsinogen I/II ratio (PGR), gastrin-17 (G-17), and Hp IgG.2,3 In East Asia and other regions with high burden of Hp infection and gastric cancer, these biomarkers have been used as screening tools for AG and IM.4 However, there exists limited data on the sensitivity and discrimination of these serologic markers in low-Hp-prevalence populations, such as the United States.

Pepsinogen II in gastritis and Helicobacter pylori infection.

BACKGROUND AND AIM: In the gastric mucosa, pepsinogen II (PgII) is produced/secreted by glands in the mucus-secreting antral and cardia compartments, but also by the chief cells and the oxyntic glands. Increasing PgII serum levels are associated with the whole spectrum of gastric inflammatory diseases, including gastritis induced by Helicobacter pylori (H. pylori). This review critically addresses the clinical value of PgII serology for assessing gastric mucosal inflammation, and as a marker of H. pylori status, in both H. pylori-positive patients and after eradication therapy. RESULTS: A search in PubMed/Scopus records yielded 39 out of 1190 published scientific studies meeting the selection criteria for this study. In the studies considered, PgII levels were significantly associated with non-atrophic gastric inflammatory lesions (p-values: 0.025-0.0001). H. pylori-positive patients had significantly higher PgII levels than H. pylori-negative individuals (p-values: 0.o5-0.0001). While a significant drop in serum PgII levels is consistently reported in H. pylori-eradicated patients (p-values: from 0.05 to 0.0001), inconsistencies in the related negative and positive predictive values significantly lower the clinical reliability of PgII testing by comparison with other available non-invasive tests. CONCLUSIONS: PgII serology may provide clinically useful information on gastric inflammatory diseases, particularly if they are non-atrophic. PgII serology is inconsistent, however, for the purposes of distinguishing patients whose H. pylori eradication therapy is successful from those who remain infected.

Gastric cancer screening: a systematic review and meta-analysis.

BACKGROUND AND AIMS: Gastric cancer (GC) screening is recommended in high-risk populations, although screening methods and intervals vary. In intermediate-risk populations, screening through esophagogastroduodenoscopy (EGD) may be considered depending on local resources. The aim of this study was to compare GC screening methods regarding effect on mortality, diagnostic yield and adherence. METHODS: Systematic review and meta-analysis including studies evaluating population-based GC screening. Search was conducted in three online databases (MEDLINE, Scopus and clinicaltrials.gov), along with manual search. RESULTS: Forty-four studies were included. Studies in upper gastrointestinal series (UGIS) demonstrated that GC screening was associated with significantly lower GC mortality rates (OR 0.63, 95% CI 0.55 - 0.73). Benefits on mortality were also found in EGD and serum pepsinogen (PG) studies. EGD was associated with significantly higher GC (0.55%, 95% CI 0.39 - 0.75%) and early-GC (EGC) detection rates (0.48%, 95% CI 0.34 - 0.65%) when compared to UGIS (GC 0.19%, 95% CI 0.10 - 0.31%; EGC 0.08%, 95% CI 0.04 - 0.13%) and PG (GC 0.10%, 95% CI 0.05 - 0.16%; EGC 0.10%, 95% CI 0.04 - 0.19%). Non-invasive methods tended to higher adherence rates when compared to EGD. Regardless of the screening method, individualized recruitment performed better. DISCUSSION: Screening positively impacted GC mortality rates. EGD was associated with higher diagnostic yield, while UGIS and PG tended to higher adherence rates. Screening uptake was predominantly impacted by recruitment strategies independently of the adopted method.

Gastric lesions in patients with autoimmune metaplastic atrophic gastritis: a retrospective study in a single center.

OBJECTIVES: The presence of autoimmune metaplastic atrophic gastritis (AMAG) may lead to an increased risk of associated gastric neoplastic lesions. This study aims to investigate the prevalence of gastric neoplasia in AMAG patients and to explore the possibility of PGI/II ratio as a predictor for AMAG diagnosis. PATIENTS AND METHODS: Retrospective audit of 135 patients diagnosed with AMAG on endoscopic gastric biopsy between January 2017 and December 2020 at Beijing Friendship Hospital. The study was registered in Chinese Clinical Trial Registry (ChiCTR2000041163). RESULTS: A total of 135 patients (the mean age 61.9 ± 10.9 years,109 female) had histologically confirmed AMAG. 31.1% (42/135) had AMAG without neoplasia on the initial biopsy; 37% (50/135) had multiple type 1 gastric neuroendocrine tumors (g-NETs), 36 grade 1 and 14 grade 2, the median diameter was 5 mm (range 1-25); 31.9% (43/135) had multiple gastric hyperplastic polyps (GHPs), including 15 cases of GHPs with neoplastic transformation, the median diameter was 14.5 mm (range 3-50). 3.7% (5/135) had single gastric low-grade dysplasia/adenoma, the median diameter was 5 mm (range 3-15). 5.9% (8/135) had single or double gastric high-grade dysplasia or adenocarcinoma, the median diameter was 15 mm (range 8-43). 40.7% (55/135) had pepsinogen (PG) I< 10 ng/ml, 45.9% (62/135) had PG I/II ratio ≤1 and each group had a median of PG I/II ratio <1. CONCLUSIONS: Lower serum PG I level and PGI/II ratio may be a predictor to indicate the diagnosis of AMAG. It's necessary to perform regular endoscopic surveillance for AMAG patients to recognize associated gastric neoplasia timely.

Evaluation of screening tests for autoimmune gastritis in histopathologically confirmed Japanese patients, and re-evaluation of histopathological classification.

BACKGROUND: The aims of the present study are to evaluate non-invasive screening tests for autoimmune gastritis (AIG) and re-evaluate histopathological classification. METHODS: We screened candidates of AIG in JCHO Shiga Hospital between May 2012 and January 2020. The screening criteria were as follows: endoscopic O-p atrophy with Updated Kimura-Takemoto classification, 3 + pepsinogen (PG) test, low serum vitamin B12 or elevated serum gastrin with positive anti-parietal cell (PC) or intrinsic factor antibodies. We evaluated the screening criteria in the patients who were histopathologically confirmed as AIG, and re-evaluated histopathological staging in clinical aspects. RESULTS: Twenty-two of 28 (78.6%) patients who met the screening criteria were histopathologically confirmed as AIG. Common clinical findings in the AIG patients were 10 × or greater anti-PC antibody, elevated serum gastrin greater than 172 pg/mL and endoscopic atrophy O-1 or greater. The areas under the curve of PG I, PG II and PG I/II ratio were 0.81, 0.29 and 0.98, respectively. Among histopathologically confirmed AIG patients, 4 and 18 patients were histopathologically classified into florid and end stages, respectively, while no patients into early stage. We could not find a significant difference between florid and end stages in the screening items studied. CONCLUSIONS: Florid and end stages in histopathological classification are both advanced-stage AIG in clinical aspects. Our screening criteria without biopsy are applicable to screen clinically-advanced AIG with 78.6% positive predictive value. PG I and PG I/II ratio may be useful to screen AIG. However, we may need other criteria to screen early stage of AIG.