A novel predictive formula for highly accurate discrimination between truly Helicobacter pylori-uninfected and currently infected/spontaneously eradicated individuals for gastric cancer screening.

The ABC classification, which categorizes gastric cancer risk based on serum Helicobacter pylori (H pylori) antibody and pepsinogen levels, has a limitation of potentially misclassifying high-risk individuals as low risk. To overcome the problem, we previously developed a 4-parameter predictive formula (age, serum H pylori antibody, PGI, and PGII) using logistic regression analysis to accurately identify low-risk truly H pylori-uninfected status. Our predictive formula demonstrated superior sensitivity and specificity in distinguishing between low-risk truly uninfected individuals and high-risk currently/spontaneously eradicated status individuals, compared to the modified ABC classification based on latex immunoassay kits (traditional 3-parameter model). This study aimed to revalidate the diagnostic accuracy of the predictive formula in a new and different study population. We applied the predictive formula to the target population and compared the sensitivity and specificity with those of the traditional 3-parameter model. A total of 788 enrollees were analyzed: 703 were classified as truly uninfected, 45 as currently infected, and 40 as spontaneously eradicated according to the results of stool antigen testing and endoscopic findings. The sensitivities and specificities of the predictive formula and the traditional 3-parameter model were 89.5% and 87.1% versus 89.8% and 80.0%, respectively. The specificity of the predictive formula was superior in the 70 to 89 age range and H pylori antibody < 3 U/mL groups. The predictive formula had higher specificity than the traditional 3-parameter model. The results should contribute to efficient gastric cancer screening by predicting H pylori infection status.

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.

Value of serum brain-derived neurotrophic factor and glial fibrillary acidic protein for detecting depression in patients with Helicobacter pylori infection.

OBJECTIVE: Infection with helicobacter pylori (H. pylori) is associated with depression, and depression can affect the outcome of H. pylori treatment. This study aimed to evaluate the value of serum brain-derived neurotrophic factor (BDNF) and glial fibrillary acidic protein (GFAP) for predicting depression in H. pylori-positive patients. METHOD: A total of 82H. pylori-positive and 82H. pylori-negative patients were recruited for this study. All patients underwent neuropsychological and gastrointestinal assessments and blood sampling. BDNF and GFAP levels were measured in serum. The least absolute shrinkage and selection operator (LASSO) model was used to determine a composite marker. RESULTS: H. pylori-positive patients showed significantly increased serum GFAP levels and significantly decreased serum BDNF levels compared to H. pylori-negative patients. Among H. pylori-positive patients, serum levels of gastrin 17 (G-17), pepsinogen (PG) I/PGII, BDNF, and GFAP, as well as Gastrointestinal Symptom Rating Scale (GSRS) scores, were significantly correlated with Hamilton Depression Scale (HAMD-24) overall scores and factor scores. Interactions between serum BDNF/GFAP and gastrointestinal serum indices or GSRS scores were significantly associated with HAMD-24 scores in H. pylori-positive patients. The LASSO model indicated that the combination of serum BDNF, GFAP, and G-17 and GSRS scores could identify H. pylori-positive patients with depression with an area under the curve of 0.879. CONCLUSION: Circulating changes in BDNF and GFAP were associated with the occurrence of depression in H. pylori-positive patients. A composite marker including neural and gastrointestinal function-related indices may be of value for identifying depression among H. pylori-positive patients.

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.

Correlation of chronic atrophic gastritis with gastric-specific circulating biomarkers.

BACKGROUND AND STUDY AIMS: It has been suggested that the combined detection of multiple serum biomarkers can effectively screen out the high-risk population of chronic atrophic gastritis in the general population. Therefore, it is necessary to establish an effective predictive model of chronic atrophic gastritis. PATIENTS AND METHODS: Serum biopsies were assessed using five stomach-specific circulating biomarkers pepsinogen I (PGI), PGII, PGI/II ratio, anti- H. pylori antibody, and gastrin-17 (G-17) to identify high-risk individuals and evaluate the risk of developing chronic atrophic gastritis. RESULTS: In the cross-sectional analysis, PGII, the PG ratio, G17, anti- H. pylori IgG were positively associated with the presence of chronic atrophic gastritis, and combined prediction of the five biomarkers was more accurate than single-factor prediction ((0.692 vs 0.54(PG1), 0.604 (PGⅡ), 0.616(PGI/II ratio), 0.629(G-17)). CONCLUSION: The combination of PGI, PGII, the PGI/II ratio, G17, and anti-H. pylori antibodies for serological analysis are helpful to screen chronic atrophic gastritis high-risk subjects from the general population and recommend that these people carry out further endoscopy and biopsy.

Utilization of an Automated Latex Agglutination Turbidity Assay for Assessing Gastric Mucosal Alteration during Helicobacter pylori Infection.

Background/Aims: : A latex agglutination turbidity (LA) assay to test for serum antibodies has been approved in Japan and Korea for mass screening of Helicobacter pylori infection. In this study, we evaluated the LA assay for diagnosing H. pylori infection and predicting gastric mucosal changes in a Mongolian population. Methods: : In total, 484 individuals were classified into H. pylori-positive (n=356) and H. pylori-negative (n=128) groups, as determined by histology and H. pylori culture. Results: : The best cutoff, sensitivity, and specificity values for the LA assay were 18.35 U/mL, 74.2%, and 65.6%, respectively. The LA values in the atrophic gastritis group were statistically higher than those in the other groups (healthy, chronic gastritis, intestinal metaplasia, and gastric cancer, p<0.0001). The cutoff value to distinguish the atrophic gastritis group from the other four groups was 32.0 U/mL, and its area under the curve was 0.673, which was the highest among the E-plate, pepsinogen (PG) I, PG II, and PG I/II ratio tests in our data. The odds ratios for atrophic gastritis determined by the LA assay and PG I test in multiple logistic regression were 2.5 and 1.9, respectively, which were significantly higher than for the other tests. Conclusions: : The LA assay can determine the risk of atrophic gastritis, which in turn is a considerable risk factor for gastric cancer. We propose using this assay in combination with the PG I/II ratio to avoid missing gastric cancer patients who have a low LA value (less than 32.0 U/mL).

Expression pattern and cellular localization of pepsinogen in early development and induced by different diets in the spotted knifejaw (Oplegnathus punctatus).

To solve the high mortality rate of early-stage larval feed conversion during aquaculture in Oplegnathus punctatus, the investigation of the structural and functional characteristics of the gastric tissue was conducted. Histological results showed that the gastric gland rudiment appeared at 17 dph. The basic structure of the stomach was fully developed between 26 and 35 dph. Two pepsinogen genes, named OpPGA1 and OpPGA2, were identified in the spotted knifejaw genome. qPCR results of developmental period showed that the two genes were low in expression during early development (5 and 15 dph). At 20 dph, the two genes started to show trace expression, and at 30 dph the mRNA expression levels of OpPGA1 and OpPGA2 reached the highest levels. Results of pepsin activity detection during the development period showed lower activity was detected 22 dph, followed by a peak at 30 dph. Under different feeding inductions, OpPGA1 showed the highest expression in the basic diet group and hard-shell group, while the expression level in the phytophagous group remained consistently low. The mRNA expression level of OpPGA2 in the phytophagous group was significantly higher than in other groups. Enzyme activity determination under different feeding inductions showed slightly higher enzyme activity in the basic diet group and crustacean group. The results of in situ hybridization showed that the mRNA of both OpPGA1 and OpPGA2 genes was both expressed in gastric gland cells. These information can contribute to the development of practical feeding methods in terms of digestive physiology for the development of larvae.

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.

Ultrasensitive fluorescence immunoassay of pepsinogen I based on enzyme-triggered decomposition of AuNCs/MnO2.

Gastric cancer is a prevalent malignant tumor of the gastrointestinal tract accompanied by a high mortality rate; therefore, early gastric cancer screening is critical for improving patient survival. In this study, we present a facile fluorescence immunoassay for highly sensitive screening of pepsinogen I (PG I) based on a one-pot biomimetic mineralization process for the synthesis of gold nanocluster-anchored manganese dioxide (AuNCs/MnO2) nanosheets. MnO2 first quenches the fluorescence of AuNCs through the Förster resonance energy transfer effect, whereas the introduction of ascorbic acid (AA) leads to the decomposition of MnO2 and rapidly recovers the fluorescence of AuNCs. Based on the above principles and phenomena, we developed a sensitive fluorescence immunoassay for the in situ generation of AA to detect PG I. Specifically, in the presence of PG I, the sandwich-type immunoreactivity-enriched alkaline phosphatase-labeled secondary antibody catalyzes the production of AA from the substrate, which enhances the fluorescence intensity. Under optimized conditions, the fluorescence intensity increased linearly with the concentration of PG I (0.05 to 200 ng mL-1) with a limit of detection (LOD) of 0.013 ng mL-1 (S/N = 3). The designed sensing platform has good stability (more than one year) and excellent anti-interference capability and demonstrates satisfactory accuracy for detection in real samples compared to commercial ELISA kits.

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.

Analysis of gastrin-17 and its related influencing factors in physical examination results.

BACKGROUND: To analyze the difference of serum gastrin-17 (G17) level in healthy people with different sex, age, and body mass index (BMI), to explore the correlation between G17 and pepsinogen, and to study the influences of Helicobacter pylori (H. pylori) infection and various inflammatory factors on G17 secretion level. METHODS: A total of 531 subjects who received physical examination in our center from April 2019 to December 2019 were enrolled in the study. All subjects were tested for G17, pepsinogen I (PGI), pepsinogen II (PGII), PGI/PGII ratio (PGR), H. pylori, serum amyloid A (SAA), C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). The difference of G17 secretion in different subjects and its correlation with PG were analyzed to investigate H. pylori infection and expound the effects of inflammatory indicators on G17. RESULTS: There was no significant difference in G17 secretion level in people with different sex, age and BMI (p > .05). G17 positively correlated with PGI and PGII, but negatively correlated with PGR. The G17 level of H. pylori-positive subjects was 10.16 ± 12.84, and prominently higher than that of H. pylori-negative subjects (3.27 ± 6.65). SAA and H. pylori infection were the greater risk factors for G17 abnormality among various indicators. CRP and ESR had no effect on G17 abnormality. CONCLUSIONS: G17 secretion is closely related to PG and H. pylori. Combined screening contributes to early screening of gastrointestinal diseases in normal people or groups at high risk for gastric cancer, but the influence of inflammatory indicators on G17 should be excluded to improve the reliability of the results.

Application of serum gastric function markers and digestive tumor indices to the diagnosis of early gastric cancer and precancerous lesions.

OBJECTIVES: To study the levels of carcinoembryonic antigen (CEA), carbohydrate antigen (CA) 199, CA724, CA242, pepsinogen (PG) I, PGII, gastrin-17 (G-17), the PGI/PGII ratio (PGR), as well as the expression of p27 and Ki67, in patients suffering from early gastric cancer and intraepithelial neoplasia and to provide new markers for the diagnosis of early gastric cancer and precancerous lesions. METHODS: A retrospective study where the blood serum concentration of CEA, CA199, CA724, CA242, PGI, PGII, G-17 and PGR were tested and also the protein expression of p27 and Ki67 was detected in patients tissues by immunohistochemistry in the Gastrointestinal Endoscopy Center of the Affiliated Hospital of Xuzhou Medical University, Xuzhou, China, from March 2018 to March 2021. RESULTS: Carbohydrate antigen 242 and CA199 levels in tumor tissue significantly differed among the groups. Pepsinogen I levels decreased with increasing disease severity, G-17 levels increased with the aggravation of severity, and p27 expression decreased with the severity. CONCLUSION: The combination of serum gastric function markers (PGI and G-17) and p27 digestive tumor indices can serve as markers for the diagnosis of early gastric cancer and intraepithelial neoplasia.

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.

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.

Endoscopic evaluation by the Kyoto classification of gastritis combined with serum anti-Helicobacter pylori antibody testing reliably risk-stratifies subjects in a population-based gastric cancer screening program.

BACKGROUND: We previously demonstrated that the Kyoto classification of gastritis was useful for judging the status of Helicobacter pylori infection in a population-based screening program, and that adding H. pylori antibody test improved its accuracy (UMIN000028629). Here, we tested whether our endoscopic diagnosis of H. pylori infection status reliably estimated gastric cancer risk in the program. METHODS: Data were collected from1345 subjects who underwent endoscopic follow-up 4 years after the end of the registration. We analyzed the association of three diagnostic methods of H. pylori infection with gastric cancer detection: (1) endoscopic diagnosis based on the Kyoto classification of gastritis; (2) serum diagnosis according to the ABC method (H. pylori antibody and pepsinogen I and II); and (3) endoscopic diagnosis together with H. pylori antibody test. RESULTS: During the follow-up, 19 cases of gastric cancer were detected. By Kaplan-Meier analysis, the detection rates of cancer were significantly higher in the past or current H. pylori infection groups than in the never-infected group with all 3 methods. By the Cox proportional hazards model, the hazard ratio for cancer detection was highest in evaluation with the combined endoscopic diagnosis and the antibody test (method 3; hazard ratio 22.6, 95% confidence interval 2.99-171) among the three methods (the endoscopic diagnosis (method 1); 11.3, 2.58-49.8, and the ABC method (method 2); 7.52, 2.49-22.7). CONCLUSIONS: Endoscopic evaluation of H. pylori status with the Kyoto classification of gastritis, especially combined with serum anti-Helicobacter pylori antibody testing, reliably risk-stratified subjects in a population-based gastric cancer screening program.

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.

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.

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.

Serum pepsinogens can help to discriminate between H. pylori-induced and auto-immune atrophic gastritis: Results from a prospective multicenter study.

BACKGROUND: Serum pepsinogen (PG) testing is recommended by the European guidelines for diagnosis of chronic atrophic gastritis (CAG). However, wide variations in diagnostic performances are observed, due to the differences in the extent of gastric atrophy, and possibly in its origin (Helicobacter pylori-, autoimmune (AIG)). AIM: To analyze the diagnostic performances of PGs testing according to these different parameters, using enzyme-linked-immunosorbent serologic assay (ELISA) and chemiluminescent immunoassay (CLEIA). METHODS: Serum samples from patients having undergone gastroscopy with biopsies in five French centers were collected prospectively. Sensitivity (Se), specificity (Sp), and Area Under Curve were analyzed according to the extent and origin of CAG. RESULTS: Overall, 344 patients (156 males [45%]; mean age 58.8 [±14.2] years) were included, among whom 44 had AIG. Diagnostic performances of PG I for the detection of corpus CAG were excellent, with Se and Sp of 92.7% and 99.1% for ELISA and 90.5% and 98.2% for CLEIA, respectively. For AIG, corresponding values were 97.7% and 97.4% for ELISA, and 95.6% and 97.1% for CLEIA. In multivariate analysis, PG levels were associated with the auto-immune origin (p<0.001) but not with the extent of the atrophic gastritis. CONCLUSIONS: Pepsinogens are highly efficient for the diagnosis of corpus-limited CAG and allow to discriminate AIG from H. pylori-induced gastritis.

Assessing the utility of pepsinogens and gastrin-17 in gastric cancer detection.

OBJECTIVES: The aim of the study was to determine the proportion of gastric cancer patients with decreased levels of pepsinogen and gastrin-17 in plasma, with the goal of providing indirect evidence of the sensitivity of these biomarkers when applied in a cancer screening setting. METHODS: The levels of pepsinogens I and II, gastrin-17, and Helicobacter pylori immunoglobulin antibodies in plasma samples of gastric cancer patients were evaluated using the GastroPanel test system (Biohit Oyj, Helsinki, Finland). A decreased level of the pepsinogen I/II ratio was defined as less than three, while a decrease in gastrin-17 was defined as less than 1 pmol/L. Univariate analysis using non-parametric tests was used to investigate differences between normal and low concentrations of biomarkers. RESULTS: In total, 481 plasma samples from patients (59.9% male) with a median age of 64 years (ranging from 27 to 88 years) were analyzed. Out of the 400 cases of gastric cancer (83.2% of the total), 182 were categorized as the intestinal type, 141 as the diffuse type, 60 as the mixed type, and 17 as indeterminate according to the Lauren classification system. The H. pylori immunoglobulin test was positive in 74.0% of the patients. Pepsinogen I/II ratio was decreased in 32.4% (36.8% of the intestinal type); gastrin-17 in 12.3% (10.1% of the antral region) of all cases. CONCLUSION: The majority of gastric cancer patients had normal levels of pepsinogen and gastrin-17, suggesting that these biomarkers have limited application as screening tools in the Caucasian population.