Catching Up with the World: Pepsinogen Screening for Gastric Cancer in the United States.

Gastric cancer remains a deadly cancer with poor outcomes in the United States. There is a need for screening strategies for gastric cancer in the U.S. population. With progressive Helicobacter pylori-mediated inflammation of the gastric mucosa, pepsinogen I levels decrease and the pepsinogen I/II ratio decreases. Pepsinogen test positivity (PG+) has been evaluated as a promising screening test among Asian and European populations; however, its utility in multiethnic U.S. populations is poorly described. In this case-control study nested within the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial, In and colleagues evaluate the discrimination of PG+ in serum collected from individuals prior to the development of gastric cancer. The authors find that PG+ individuals were at nearly 10-fold increased risk for developing gastric cancer, and this effect remained robust after adjusting for Helicobacter pylori status, family history, education, smoking, and obesity. In subgroup analysis, the predictive ability of the test was particularly robust for noncardia gastric cancers, and nonpredictive of cardia gastric cancers. Serum pepsinogen testing holds promise as a noninvasive screening strategy to triage individuals at heightened risk for gastric cancer, and may help to improve early diagnosis in the United States. See related article by In et al., p. 1426.

Gastric cancer detection using the serum pepsinogen test method.

BACKGROUND: Gastric cancer (GC) is the eighth most common cause of cancer deaths in Croatia and one of the most common causes of cancer deaths worldwide. A reliable diagnostic tool for the early detection of GC is essential. OBJECTIVE: We previously suggested a pepsinogen test method to reduce the mortality from GC by allowing early detection. Here, we report an updated analysis from a prospective single-center clinical study to evaluate the sensitivity and specificity of the pepsinogen test method and to determine whether this test can be used as a part of routine laboratory assessment of high-risk patients. METHODS: We present mature data of the pepsinogen test method in the Croatian population after a median follow-up of 36 months. Statistical analyses were performed using a Mann-Whitney U test, multiple logistic regression, and receiver operating characteristics (ROC) to evaluate the predictive power of the assayed biomarkers. RESULTS: Of the 116 patients, 25 patients had GC and 91 demonstrated a nonmalignant pathology based on tissue biopsy. Cutoff values were pepsinogen I ⩽70 and pepsinogen I/II ratio ⩽3.0. Using ROC curve analysis, the accuracy, sensitivity, specificity, positive predictive value, and negative predictive value were determined to be 87.22%, 78.12%, 90.10%, 71.43%, and 92.86%, respectively, for the diagnosis of GC. The area under the curve was 0.700 (95% confidence interval 0.57-0.83). CONCLUSION: Pepsinogen tests are valuable for screening a population in need of further diagnosis and could help to avoid unnecessary invasive endoscopic procedures.

Diagnostic value of MRI-DWI signal intensity value combined with serum PGI, PGII and CA199 in early gastric cancer.

To explore the diagnostic value of MRI-DWI signal intensity value combined with serum PGI. PGII and CA199 in early gastric cancer. Sixty cases of gastric cancer patients admitted to our hospital from December 2019 to December 2020 were selected as the gastric cancer group and 80 cases of healthy volunteers who underwent physical examination in our hospital during the same period were selected as the healthy group. All the 60 patients underwent MRI-DWI examination, and the pathological diagnosis results were regarded as the gold standard. MRI-DWI images, MRI-DWI signal intensity values of patients with different degrees of gastric cancer differentiation. Serum PGI, PGII and CA199 levels of subjects in the two groups were compared. AUC was used to evaluate the diagnostic value of MRI-DWI signal intensity value combined with serum PGI, PG II and CA199 for early gastric cancer. In the healthy group, T1W1 showed relatively uniform low signal intensity. While T2WI showed no significant increase in signal intensity. In the gastric cancer group. There was diffuse gastric wall thickening, local thickening or mass formation; T1WI and WATS showed slightly lower signal intensity in the lesion area. T2WI, FLAIR and B-TFE showed slightly uneven or moderately increased signal intensity. DWI showed limited diffusion, and the signal intensity increased uniformly or more uniformly, and the range of increase was clear. The signal intensity of MRI-DWI was 89.12 ± 8.14 in patients with low differentiation, 82.17 ± 6.35 in patients with moderate differentiation, and 74.52 ± 4.53 in patients with high differentiation. There were significant differences in the signal intensity of MRI-DWI among the three groups, and the difference was statistically significant (F=12.214, P <0.05). Serum PGI levels of subjects in the gastric cancer group were significantly lower than those in the healthy group, and the levels of PGII and CA199 were significantly higher than that in the healthy group, with statistical significance (P <0.05). The AUC, sensitivity and specificity of MRI-DWI signal intensity value and serum PGI, PGII and CA199 combined indexes in the diagnosis of gastric cancer were significantly higher than those of the independent indexes, with statistical significance (P <0.05). Conclusion: MRI-DWI signal strength value, serum PGI, PGII and CA199 levels are closely related to the occurrence and development of early gastric cancer. The combined detection and diagnosis efficiency is higher, which is helpful to improve the detection rate of early gastric cancer and is worthy of extensive clinical application.

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.

Mitochondrial DNA Copy Number Variations and Serum Pepsinogen Levels for Risk Assessment in Gastric Cancer

Background: Variations in mitochondrial DNA copy number (mtDNA-CN) of peripheral blood leukocytes (PBLs), as a potential biomarker for gastric cancer (GC) screening has currently been subject to controversy. Herein, we have assessed its efficiency in GC screening, in parallel and in combination with serum pepsinogen (sPG) I/II ratio, as an established indicator of gastric atrophy. Methods: The study population included GC (n = 53) and non-GC (n = 207) dyspeptic patients. The non-GC group was histologically categorized into CG (n = 104) and NM (n = 103) subgroups. The MtDNA-CN of PBLs was measured by quantitative real-time PCR. The sPG I and II levels and anti-H. pylori serum IgG were measured by ELISA. Results: The mtDNA-CN was found significantly higher in GC vs. non-GC (OR = 3.0; 95% CI = 1.4, 6.4) subjects. Conversely, GC patients had significantly lower sPG I/II ratio than the non-GC (OR = 3.2; CI = 1.4, 7.2) subjects. The combination of these two biomarkers yielded a dramatic amplification of the odds of GC risk in double-positive (high mtDNA-CN-low sPGI/II) subjects, in reference to double-negatives (low mtDNA-CN-high sPGI/II), when assessed against non-GC (OR = 27.1; CI = 5.0, 147.3), CG (OR = 13.1; CI = 2.4, 72.6), or NM (OR = 49.5; CI = 7.9, 311.6) groups. Conclusion: The combination of these two biomarkers, namely mtDNA-CN in PBLs and serum PG I/II ratio, drastically enhanced the efficiency of GC risk assessment, which calls for further validations.

Scoring model for discriminating gastric cancer risk in patients with negative serum pepsinogen and anti-Helicobacter pylori antibody results.

BACKGROUND: The ABC test measures serum pepsinogen and anti-Helicobacter pylori IgG antibody levels to predict precancerous conditions in the stomach and gastric cancer. However, a limitation of this test is that the gastric cancer risk is not negligible in patients with a negative result. METHODS: Based on their ABC results, 1157 patients were classified into Groups A (n = 392), B (n = 479), C (n = 247), and D (n = 39). In Group A, 24.2% of patients had atrophic gastritis and/or intestinal metaplasia and had thus been incorrectly assigned to Group A. Patients in Group A were then assigned to derivation (n = 236) and validation (n = 156) cohorts by 3:2 random sampling. Logistic regression analyses were performed to identify the factors discriminating between a correct (true) and incorrect (false) Group A classification. RESULTS: A 4-point discriminative model was constructed based on a high-negative H. pylori IgG antibody titer and the patient's age (50-64 and ≥65 years). The areas under the receiver operating characteristic curve for the derivation and validation cohorts were 0.868 and 0.894, respectively. In the validation cohort, the addition of a discriminative model score ≥2 to the ABC method showed a similar accuracy for predicting gastric cancer risk compared with the ABC method alone (93.8% vs. 92.4%). CONCLUSION: The 4-point discriminative model may help identify patients with a normal serological test who are nonetheless at risk of developing gastric cancer.

A point-of-care chemiluminescence immunoassay for pepsinogen I enables large-scale community health screening.

Pepsinogen I (PGI) can reflect the morphology and function of the gastric mucosa. Accordingly, the large-scale community health screening of PGI can dramatically increase the early diagnosis rate of gastric cancer. However, PGI testing can only be carried out in comprehensive hospitals and health examination centers. To ameliorate this issue, a point-of-care chemiluminescent immunoassay for PGI was developed in a fully automated miniaturized instrument. This instrument was especially developed for health check-ups in the grassroots communities; its volume of which is only 0.18 m3. Critically, the entire detection process for a single sample only requires 20 min, and the samples can be loaded continuously, making the method suitable for high-throughput analysis. The assay displayed an excellent detection limit of 0.048 ng/mL with a broad detection range of 0-200 ng/mL. Furthermore, this assay exhibited high sensitivity and specificity, had low intra- and inter-assay coefficients of variation (<10%), and was not affected after storage at 37 °C for 7 days. The assay was used to detect PGI in 95 clinical serum samples, and the results were highly correlated with those that were clinically tested (correlation coefficient, R2 = 0.998). Hence, the method established in this work has great application value and can be broadly applied for the large-scale screening of gastric cancer in resource-limited areas.

Helicobacter pylori, clinical, laboratory, and noninvasive biomarkers suggestive of gastric damage in healthy school-aged children: A case-control study.

BACKGROUND: Helicobacter pylori is acquired largely in early childhood, but its association with symptoms and indirect biomarkers of gastric damage in apparently healthy children remains controversial. We aimed to relate persistent H. pylori infection in apparently healthy school-aged children with clinical, laboratory, and noninvasive biomarkers suggestive of gastric damage using a case-control design. MATERIALS AND METHODS: We followed up 83 children aged 4-5 years with persistent H. pylori infection determined by stool antigen detection and/or a urea breath test and 80 noninfected matched controls from a low-income to middle-income, periurban city in Chile for at least 3 years. Monitoring included clinical visits every 4 months and annual assessment by a pediatric gastroenterologist. A blood sample was obtained to determine laboratory parameters potentially associated with gastric damage (hemogram and serum iron and ferritin levels), biomarkers of inflammation (cytokines, pepsinogens I and II, and tissue inhibitor metalloproteinase 1), and expression of cancer-related genes KLK1, BTG3, and SLC5A8. RESULTS: Persistently infected children had higher frequency of epigastric pain on physical examination (40% versus 16%; P = 0.001), especially from 8 to 10 years of age. No differences in anthropometric measurements or iron-deficiency parameters were found. Persistent infection was associated with higher levels of pepsinogen II (median 12.7 ng/mL versus 9.0 ng/mL; P < 0.001); no difference was observed in other biomarkers or gene expression profiles. CONCLUSIONS: H. pylori infection in apparently asymptomatic school-aged children is associated with an increase in clinical symptoms and in the level of one significant biomarker, pepsinogen II, suggesting early gastric involvement.

Immunostimulatory membrane proteins potentiate H. pylori-induced carcinogenesis by enabling CagA translocation.

Infection with Helicobacter pylori is the single greatest risk factor for developing gastric adenocarcinoma. In prospective, population-based studies, seropositivity to the uncharacterized H. pylori proteins Hp0305 and Hp1564 was significantly associated with cancer risk in East Asia. However, the mechanism underlying this observation has not been elucidated. Here, we show that Hp0305 and Hp1564 act in concert with previously ascribed H. pylori virulence mechanisms to orchestrate cellular alterations that promote gastric carcinogenesis. In samples from 546 patients exhibiting premalignant gastric lesions, seropositivity to Hp0305 and Hp1564 was significantly associated with increased gastric atrophy across all stomach conditions. In vitro, depletion of Hp0305 and Hp1564 significantly reduced levels of gastric cell-associated bacteria and markedly impaired the ability of H. pylori to stimulate pro-inflammatory cytokine production. Remarkably, our studies revealed that Hp1564 is required for translocation of the oncoprotein CagA into gastric epithelial cells. Our data provide experimental insight into the molecular mechanisms governing novel H. pylori pathogenicity factors that are strongly associated with gastric disease and highlight the potential of Hp0305 and Hp1564 as robust molecular tools that can improve identification of individuals that are highly susceptible to gastric cancer. We demonstrate that Hp0305 and Hp1564 augment H. pylori-mediated inflammation and gastric cancer risk by promoting key bacteria-gastric cell interactions that facilitate delivery of oncogenic microbial cargo to target cells. Thus, therapeutically targeting microbial interactions driven by Hp0305/Hp1564 may enable focused H. pylori eradication strategies to prevent development of gastric malignancies in high-risk populations.

Associations of Serum Pepsinogens and Helicobacter Pylori Infection with High-Sensitivity C-Reactive Protein in Medical Examination Population.

OBJECTIVE: This study aimed to clarify the distribution characteristics of serum pepsinogen (PG) and Helicobacter pylori in the medical examination population and to explore the relationships of PG level and H. pylori infection status with the high-sensitivity C-reactive protein (hsCRP) level and their significance in health examination. METHODS: We detected H. pylori infection by C13 urea breath test, the serum pepsinogen I (PGI) and pepsinogen II (PGII) contents were measured by chemiluminescence microparticle immunoassay, and the PGI/PGII ratio was calculated. In addition, the serum hsCRP level was determined by the Abbott C16000 automatic biochemical analyzer. RESULTS: The PGI and hsCRP levels were significantly higher in men than in women, and the PGII level was slightly higher in men than in women (both P <.05). The PGI, PGII, and hsCRP levels were positively correlated with age (r = 0.210, 0.287, and 0.133, respectively; P <.05), whereas the PGI/PGII ratio was negatively correlated with age (r = -0.190; P <.05). The positive H. pylori infection rate was 30.2% among the patients in this study; H. pylori infection was not related to sex (P >.05), and the difference in age stratification was not statistically significant (P >.05). The abnormal PGI/PGII ratio in the medical examination population was not correlated with sex (P >.05). In the H. pylori positive infection group, the proportion of PGI/PGII ratio <3, the PGI and PGII levels were significantly higher than those in the H. pylori negative infection group, and the PGI/PGII ratio was significantly lower than that in the negative group (both P <.05). The hsCRP level was not associated with H. pylori infection (P >.05), and it was significantly higher in the PGI/PGII ratio <3 group than in the PGI/PGII ratio ≥3 group (P <.05). CONCLUSION: The PGI and PGII levels and the PGI/PGII ratio are correlated with H. pylori infection. The abnormal PGI/PGII ratio is closely related to H. pylori infection and hsCRP level. Therefore, H. pylori infection status and hsCRP level should be considered when determining atrophic gastritis by the PGI/PGII ratio.

Association between serum pepsinogen and atherosclerotic cardiovascular disease.

BACKGROUND AND AIM: Serum pepsinogens (PGs) are biomarkers for gastric mucosal damage and have been reported to be associated with atherosclerosis. Its correlation with atherosclerotic cardiovascular disease (ASCVD) is still unknown. This study aimed to explore the association between serum PGs and ASCVD for providing physicians with an integrative picture to make rational plans in the diagnosis and treatment of ASCVD. METHODS AND RESULTS: The concentrations of serum PGs and their distributions between ASCVD and non-ASCVD were compared by non-parametric test, Chi-squared test and Fisher exact test. The correlation between variables was analyzed by Spearman's correlation test. The association of serum PGs with ASCVD was analyzed by the binary logistic regression and two-piecewise linear regression. A total of 8355 recruited cases were eligible for the study. The concentrations of serum PGs were significantly different between the ASCVD and non-ASCVD groups (P = 0.025, P < 0.001). The lower PGI and PGR levels were significantly correlated with a high risk of ASCVD presence after adjustment for 26 potential covariates. Moreover, there was a linear relationship between the high level of PGII and the high risk of ASCVD [adjusted OR = 1.16 (1.00, 1.37), P = 0.07]. A nonlinear relationship of PGI/PGR and ASCVD (P = 0.08/<0.001) was also revealed. The risk of ASCVD increased with a range of log PGI ≥2.13 (PGI≥131 ng/mL) [adjusted OR = 4.67 (1.00, 23.17)], and decreased with a range of log PGR ≥0.22 (1.65) [adjusted OR = 0.59 (0.48, 0.74), P < 0.001]. CONCLUSIONS: Serum PGI and PGR are nonlinearly correlated with ASCVD, while PGII is linearly correlated with ASCVD. Among all PGs, PGR may serve as a reliable biomarker for ASCVD.

Serum Gastrin Predicts Hydrogen-Producing Small Intestinal Bacterial Overgrowth in Patients With Abdominal Surgery: A Prospective Study.

OBJECTIVES: Small intestinal bacterial overgrowth (SIBO) might be associated with a history of abdominal surgery. We aimed to evaluate the prevalence of SIBO and to investigate serum gastrin and pepsinogen as predictors of SIBO in patients with a history of hysterectomy, gastrectomy, or cholecystectomy. METHODS: This prospective study surveyed 146 patients with a history of hysterectomy, gastrectomy, or cholecystectomy, and 30 healthy controls, who underwent a hydrogen (H2)-methane (CH4) glucose breath test (GBT) for SIBO. Serum pepsinogen I and II and gastrin levels were reviewed. RESULTS: GBT positivity (+) was significantly higher in patients with histories of abdominal surgery than that in in controls (37.6% vs 13.3%, P < 0.01). Among GBT+ patients, 36.0% (18/50), 96.2% (25/26), and 17.1% (12/70) were in the hysterectomy, gastrectomy, and cholecystectomy groups, respectively. Among the GBT subtypes, 43.6% (24/55), 10.9% (6/55), and 45.5% (25/55) of patients were in the GBT(H2)+, GBT(CH4)+, and GBT(mixed)+ groups, respectively. The gastrectomy group had significantly more GBT+ or GBT(H2)+ patients than the other surgical groups. Gastrin levels were higher in GBT(H2)+ patients and lower in GBT(CH4)+ patients than those in GBT- patients. Previous gastrectomy and elevated gastrin levels were independent predictive factors of GBT(H2)+. DISCUSSION: SIBO is not uncommon in patients with histories of abdominal surgeries, but it is more common in patients who have undergone gastrectomy. Serum gastrin level could be a serologic predictor of H2-producing SIBO. The relationship between serum gastrin and SIBO requires further research.

Low Pepsinogen I/II Ratio and High Gastrin-17 Levels Typify Chronic Atrophic Autoimmune Gastritis Patients With Gastric Neuroendocrine Tumors.

INTRODUCTION: Chronic atrophic autoimmune gastritis (CAAG) can lead to the development of gastric neuroendocrine tumors (gNETs) and can be accompanied by other autoimmune diseases. This study aimed to determine, in CAAG patients, the association of gNET development, the prevalence of autoimmune diseases other than CAAG, the association of autoimmunity, and gNET development with pepsinogen I, II, gastrin-17, and Helicobacter pylori infection analysis. METHODS: We determined the prevalence of gNETs and other autoimmune diseases and analyzed pepsinogen I and II, gastrin-17 serum levels, and H. pylori infection in all patients diagnosed with CAAG at our hospital between 2013 and 2017. RESULTS: A total of 156 patients were studied and in 15.4% was observed concomitant gNET. Approximately 68.6% had at least 1 other autoimmune disease at diagnosis of CAAG. Approximately 60.9% had autoimmune thyroiditis, followed by diabetes (19.9%) and autoimmune polyendocrine syndrome (12.8%). CAAG patients with and without gNET had similar rates of comorbidity with other autoimmune diseases, but the pepsinogen I/II ratio was lower in patients with gNET (1.6 vs 4.5, P = 0.018). Receiver operating characteristic curve analyses identified a pepsinogen I/II ratio <2.3 and gastrin-17 levels >29.6 pmol/L as cutoffs distinguishing CAAG patients with gNET from those without. The combined use of these cutoff correctly identified 16 of the 18 CAAG patients with gNET (P = 0.007). H. pylori infection was observed in 28.7% of cases tested but did not associate with gNET. DISCUSSION: This study suggests that a low pepsinogen I/II ratio and high gastrin-17 levels characterize patients with CAAG and gNET and confirms the frequent coexistence of CAAG with other autoimmune diseases.

Prediction of true Helicobacter pylori-uninfected status using a combination of age, serum antibody and pepsinogen: Logistic regression analysis.

INTRODUCTION: To prevent gastric cancer, it is important to accurately determine the presence of Helicobacter pylori (HP) infection. However, correctly identifying HP-uninfected individuals is difficult when using the combination of HP antibody and pepsinogen (PG). OBJECTIVE: The aim of this study was to discriminate true HP-uninfected individuals from others without the need for endoscopic examination. METHODS: A total of 684 subjects with no history of HP eradication who underwent a medical checkup at our hospital were enrolled. The "true uninfected individuals" were determined by a negative stool antigen test and no endoscopic findings of HP-associated gastritis. HP antibody was measured by the latex immunoassay method. Logistic regression analysis using a combination of noninvasive parameters was performed to develop a formula for predicting true uninfected individuals. RESULTS: A total of 528 subjects were classified as true uninfected individuals. Logistic regression analysis showed that statistically significant factors for true uninfected individuals were age (p < 0.001), HP antibody (p <0.001), PGI (p <0.001), and PGII (p = 0.012). The areas under the curve (AUCs) for true uninfected individuals were the highest (0.944) upon applying the prediction formula including four parameters: age, HP antibody, PGI, and PGII. Both the sensitivity and the specificity of the four-parameter prediction formula were higher than those of the traditional three-parameter model using HP antibody, PGI, and PGI/II ratio (sensitivity: 93.2% vs. 86.6% and specificity: 88.5% vs. 82.7%). CONCLUSIONS: Our findings suggest that a model with a combination of four noninvasive parameters is useful for predicting true HP-uninfected individuals without the need for endoscopic examination.

Autoantibodies Toward ATP4A and ATP4B Subunits of Gastric Proton Pump H+,K+-ATPase Are Reliable Serological Pre-endoscopic Markers of Corpus Atrophic Gastritis.

INTRODUCTION: Noninvasive assessment of corpus atrophic gastritis (CAG), a condition at increased risk of gastric cancer, is based on the measurement of pepsinogens, gastrin, and Helicobacter pylori antibodies. Parietal cell autoantibodies (PCAs) against the gastric proton pump (ATP4) are potential serological biomarkers of CAG. The purpose of this study was to compare the diagnostic performance of PCA and pepsinogen I tests in patients with clinical suspicion of CAG with the histopathological evaluation of gastric biopsies as reference standard. METHODS: A prospective case-finding study was performed on 218 naive adult patients (131 women, median age 65 years) who underwent gastric biopsies to confirm/exclude CAG. Patients with histopathological CAG were defined as cases, conversely as controls. Autoantibodies against the individual alpha (ATP4A) and beta (ATP4B) subunits of ATP4 were measured by luciferase immunoprecipitation, and global PCA and pepsinogen I by enzyme-linked immunosorbent assay. RESULTS: Histopathology classified 107 subjects (49%) as cases (CAG+, autoimmune 81.2%, and multifocal extensive 18.8%) and 111 subjects (51%) as controls (CAG-). In cases, ATP4A, ATP4B, and PCA titers were increased compared with controls, whereas pepsinogen I was reduced (P < 0.0001 for all). ATP4B, ATP4A, and pepsinogen I tests showed sensitivities of 77%, 75%, and 73% and specificities of 88%, 88%, and 80%, respectively. The receiver operating characteristic (ROC) area under the ROC curve (AUC) of these serological biomarkers confirmed their ability to discriminate cases from controls (ATP4B = 0.838, ATP4A = 0.826, pepsinogen I = 0.775, and PCA = 0.805), whereas the partial ROC-pAUC90 analysis showed that the ATP4B test had the best diagnostic performance (P = 0.008 vs ATP4; P = 0.0002 vs pepsinogen I). The presence of autoimmune or extensive gastritis was not significantly different between ATP4B positive or negative cases (P = 0.217). DISCUSSION: PCAs are promising serological biomarkers for the identification of CAG in high-risk individuals, particularly in an autoimmune pattern but also in an extensive-multifocal atrophy pattern.

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.

Associations of Helicobacter pylori seropositivity and gastric inflammation with pediatric asthma.

OBJECTIVE: Controversy exists regarding an association between Helicobacter pylori infection and asthma in children. We examined the hypotheses of inverse associations of H. pylori seroprevalence and pepsinogen (PG) levels, as markers of gastric inflammation, with asthma in children. METHODS: A hospital-based case-control study was conducted among children aged 4.8 to 17.3 years in Israel. Confirmed asthma cases (n = 75) were recruited through a pulmonary clinic, and controls (n = 160) without asthma were enrolled. Using enzyme-linked immunosorbent assays we measured the presence of H. pylori immunoglobulin G (IgG) antibodies, IgG antibodies to cytotoxin-associated gene A antigen (CagA) (virulent factor), serum PG levels and exposure to other enteric pathogens (Shigella flexneri). Multivariable logistic regression models were applied. RESULTS: H. pylori IgG seropositivity was 25% and 40% among cases and controls, respectively (P = .03). H. pylori CagA IgG seropositivity was associated with reduced risk of asthma (adjusted odds ratio [OR], 0.33 [95% CI, 0.11-0.95] but not for the CagA negative serology (adjusted OR, 0.70 [95% CI, 0.32-1.54]). Children who were H. pylori seropositive with a PGI:PGII of ≤6.78 (severe gastric inflammation) had a lower likelihood of asthma (adjusted OR, 0.31 [95% CI, 0.10-0.89]) than did seronegative children. Exposure to Shigella flexneri did not differ between cases and controls, nor according to H. pylori seropositivity. Among the asthmatic children, pulmonary function did not differ according to H. pylori seropositivity. CONCLUSIONS: H. pylori infection and its related gastric inflammation may have a protective role in the risk of pediatric asthma and further research into a potential causal pathway is required.

The Role of Helicobacter pylori and Serum Pepsinogen Levels in Metachronous Gastric Cancer After Endoscopic Gastrectomy.

PURPOSE: The current study aimed to explore the role of Helicobacter pylori (Hp) infection and serum pepsinogen (PG) levels in the occurrence of metachronous gastric cancer after endoscopic gastrectomy. MATERIALS AND METHODS: Totally, 50 patients with metachronous gastric cancer, 50 patients with chronic atrophic gastritis and 50 healthy subjects were collected from October 2015 to October 2018. Patients in the gastric cancer group underwent endoscopic gastrectomy. Serum samples were collected for detection and correlation analysis of serum PG I, PG II, and Hp. In addition, the contents of serum PG and gastrin and postoperative adverse events were statistically analyzed. RESULTS: There was a statistically significant difference in serum PG I levels, positive Hp infection rate, the number of mast cells, plasma motilin levels and postoperative adverse events among the 3 groups (P<0.01). There was also a significant difference in PG II levels among the groups (P<0.05). On the basis of the results, the amount of inflammatory cells in the gastric cancer group was significantly higher than that in the gastritis group, and there was a remarkable difference in gastric cancer patients before and after operation. Through data analysis, it was found that the levels of PG I and II were the highest in the healthy control group and the lowest in the gastric cancer group, the number of mast cells was the largest in the gastric cancer group, and the level of motilin was the highest in the healthy control group. CONCLUSION: Hp infection and serum PG levels are associated with metachronous gastric cancer.

Optimized diagnosis of Helicobacter pylori and tailored eradication therapy for preventing gastric cancer: a proposal for SHAKE strategy.

INTRODUCTION: To decrease gastric cancer-related mortality, the Korean National Cancer Screening Program provides biennial screening gastroscopy to all individuals aged >40 years. However, a test-and-treat strategy of Helicobacter pylori for preventing gastric cancer has not been established. AREAS COVERED: In this review, we present up-to-date results of endoscopic findings of H. pylori gastritis, optimal sites for H. pylori detection, gastric cancer risk assessment using serum pepsinogen, tailored eradication based on the antimicrobial resistance against H. pylori, and post-eradication surveillance. EXPERT OPINION: Here we propose approaches to H. pylori diagnosis and treatment for preventing gastric cancer, termed 'Screening for H. pylori in Korea and Eradication (SHAKE)' strategy. This strategy consists of the following: (1) optimized H. pylori diagnosis, (2) individualized management based on the H. pylori infection status, and (3) tailored eradication therapy. H. pylori gastritis can be diagnosed by endoscopic observation of the gastric mucosal pattern at the greater curvature of the corpus. Measurement of the serum pepsinogen I/II ratio is useful for assessing the risk of gastric cancer. As a first-line treatment, tailored eradication based on the results of molecular testing is effective in a country with a high rate of clarithromycin-resistant H. pylori.

[Effect of heat-sensitive moxibustion at "Zhongwan" (CV 12) on serum GH and PG in chronic atrophic gastritis rats].

OBJECTIVE: To observe the effect of heat-sensitive moxibustion at "Zhongwan" (CV 12) on serum growth hormone (GH) and pepsinogen (PG) in chronic atrophic gastritis (CAG) rats, and to explore the potential mechanism of heat-sensitive moxibustion for CAG. METHODS: A total of 66 male SD rats were randomized into a blank group (12 rats) and a model establishment group (54 rats). No intervention was given in the blank group. Rats in the model establishment group were intervented with compound pathogeny method for 12 weeks to establish CAG model, which were further divided into a model group (11 rats), a vitacoenzyme group (11 rats) and a moxibustion group (22 rats). In the moxibustion group, suspending moxibustion was applied at "Zhongwan" (CV 12) for 40 min. After the intervention of moxibustion, 0.9% sodium chloride solution was given by gavage (2 mL·kg-1·d-1). According to the changes of tail temperature, rats in the moxibustion group were divided into a heat-sensitive moxibustion group (11 rats) and a non-heat-sensitive moxibustion group (8 rats). The vitacoenzyme group was given vitacoenzyme as the same dose by gavage. The intervention was adopted once a day for 28 days. Changes of body weight were observed among the groups. Expressions of serum GH, PGⅠand PGⅡwere detected by ELISA, and the ratio of PGⅠand PGⅡ (PGR) was calculated. The morphological changes of gastric mucosa were observed by macroscopy and light microscope. RESULTS: ①After modeling, the body weight of rats in the model establishment group was lower than the blank group (P<0.01). Compared with the model group, the body weight of rats in the vitacoenzyme group, the heat-sensitive moxibustion group and the non-heat-sensitive moxibustion group was increased after intervention (P<0.05), and there were no significant differences among the intervention groups (P>0.05). ②Under macroscopy and light microscope, gastric tissue of rats after modeling showed dark red and pale gastric mucosa, lower plica and mucosal congestion. The glands of lamina propria were atrophied or disappeared with sparse and disordered arrangement, in which, lymphoid follicles and inflammatory cells could be observed. After intervention, morphology of gastric mucosa was improved in the vitacoenzyme group, the heat-sensitive moxibustion group and the non-heat-sensitive moxibustion group. ③Compared with the blank group, the serum levels of GH, PGⅠ, PGⅡ and PGR were decreased in the model group (P<0.05, P<0.01). Compared with the model group, the serum levels of GH, PGⅠand PGⅡwere increased in the vitacoenzyme group, the heat-sensitive moxibustion group and the non-heat-sensitive moxibustion group (P<0.05, P<0.01), the levels of PGR were increased without statistical difference (P>0.05). Compared with the vitacoenzyme group and the non-heat-sensitive moxibustion group, the serum levels of GH and PGⅠwere increased in the heat-sensitive moxibustion group (P<0.05). CONCLUSION: Heat-sensitive moxibustion at "Zhongwan" (CV 12) can improve the morphology of gastric mucosa in chronic atrophic gastritis rats, its mechanism may be related to the up-regulation of serum GH and PGⅠ.