Non-atrophic Gastritis Group Research Articles

Serum proteomic profiling of precancerous gastric lesions and early gastric cancer reveals signatures associated with systemic inflammatory response and metaplastic differentiation.

The noninvasive detection technique using serum for large-scale screening is useful for the early diagnosis of gastric cancer (GC). Herein, we employed liquid chromatography mass spectrometry to determine the serum proteome signatures and related pathways in individuals with gastric precancerous (pre-GC) lesions and GC and explore the effect of Helicobacter pylori (H. pylori) infection. Differentially expressed proteins in GC and pre-GC compared with non-atrophic gastritis (NAG) group were identified. APOA4, a protein associated with metaplastic differentiation, and COMP, an extracellular matrix protein, were increased in the serum of patients with pre-GC lesions and GC. In addition, several inflammation-associated proteins, such as component C3, were decreased in the GC and pre-GC groups, which highlight a tendency for the inflammatory response to converge at the gastric lesion site during the GC cascade. Moreover, the abundance of proteins associated with oxidant detoxification was higher in the GC group compared with that in the NAG group, and these proteins were also increased in the serum of the H. pylori-positive GC group compared with that in the H. pylori-negative GC patients, reflecting the importance of oxidative stress pathways in H. pylori infection. Collectively, the findings of this study highlight pathways that play important roles in GC progression, and may provide potential diagnostic biomarkers for the detection of pre-GC lesions.

U-Net deep learning model for endoscopic diagnosis of chronic atrophic gastritis and operative link for gastritis assessment staging: a prospective nested case–control study

Background: The operative link for the gastritis assessment (OLGA) system can objectively reflect the stratification of gastric cancer risk in patients with chronic atrophic gastritis (CAG). Objectives: We developed a real-time video monitoring model for the endoscopic diagnosis of CAG and OLGA staging based on U-Net deep learning (DL). To further validate and improve its performance, we designed a study to evaluate the diagnostic evaluation indices. Design: A prospective nested case–control study Methods: Our cohort consisted of 1306 patients from 31 July 2021 to 31 January 2022. According to the pathological results, patients in the cohort were divided into the CAG group and the chronic non-atrophic gastritis group to evaluate the diagnostic evaluation indices. Each atrophy lesion was automatically labeled and the atrophy severity was assessed by the model. Propensity score matching was used to minimize selection bias. Results: The diagnostic evaluation indices and the consistency between OLGA staging and pathological diagnosis of the model were superior to those of endoscopists [sensitivity (89.31% versus 67.56%), specificity (90.46% versus 70.23%), positive predictive value (90.35% versus 69.41%), negative predictive value (89.43% versus 68.40%), accuracy rate (89.89% versus 68.89%), Youden index (79.77% versus 37.79%), odd product (79.23 versus 4.91), positive likelihood ratio (9.36 versus 2.27), negative likelihood ratio (0.12 versus 0.46)], areas under the curves (AUC) (95% CI) (0.919 (0.893–0.945) versus 0.749 (0.707–0.792), p < 0.001) and kappa (0.816 versus 0.291)]. Conclusion: Our study demonstrated that the DL model can assist endoscopists in real-time diagnosis of CAG during gastroscopy and synchronous identification of high-risk OLGA stage (OLGA stages III and IV) patients. Trial registration: ChiCTR2100044458.

Serum exosomal miR-122-5p, GAS, and PGR in the non-invasive diagnosis of CAG.

ObjectiveThe aim of this study was to integrate the serum exosomal miRNA miR-122-5p with canonical serological biomarkers for the non-invasive screening of chronic atrophic gastritis (CAG) patients.MethodsmiR-122-5p and U6 were amplified by the quantitative reverse transcription polymerase chain reaction (RT-qPCR), gastrin (GAS), pepsinogen I (PG-I), and PG-II and were measured by ELISA. The area under the receiver operating characteristic (ROC) curves and their correlation were analyzed.ResultsIn the present study, GAS level and PG-I/PG-II ratio (PGR) were increased in CAG group, but there was no significant difference in PG-I or PG-II levels between CAG group and chronic non-atrophic gastritis (CNAG) group. Only GAS level and PG-I/PG-II ratio were significantly correlated with atrophy, and not any other clinicopathologic factors. Expression of hsa-miR-122-5p positively correlated with GAS level, PG-I level, and PGR, while it negatively correlated with PG-II level; however, none of them had significant difference. The combination of GAS, PGR, and hsa-miR-122-5p presented as a better model for non-invasive screening of CAG compared to others.ConclusionThese results suggested that serum exosomal hsa-miR-122-5p combined with GAS and PGR would elevate accuracy and specificity in non-invasive screening of CAG.

Psychoanalysis of 300 patients with chronic gastritis

Objective To analyze the difference of psychosocial characteristics in patients with chronic gastritis. Methods From June to December 2018, a total of 300 patients with chronic gastritis visited Xijing Hospital were consecutively enrolled. The patients were divided into chronic non-atrophic gastritis (CNAG) group, chronic atrophic gastritis (CAG) group and CAG with intestinal metaplasia group, with 100 cases in each group. Hamilton anxiety scale (HAMA), Hamilton depression scale (HAMD), living events scale (LES) and Eysenck personality questionnaire (EPQ) were used for evaluation and analysis. Chi square test, analysis of variance, nonparametric rank sum test and Kruskal Wallis H test were used for statistical analysis. Results The incidences of anxiety of the CAG group and the CAG with intestinal metaplasia group were both significantly higher than that of the CNAG group (64.0%, 64/100; 53.0%, 53/100; and 34.0%, 34/100; respectively), and the differences were statistically significant (χ2=0.007 and 0.001, both P 56.7) of etraversion or introversion and concealment in CAG group and the CAG with intestinal metaplasia group were higher than those in the CNAG group (48.0%, 48/100; 23.0%, 23/100; 4.0%, 4/100 and 46.0%, 46/100; 21.0%, 21/100 and 7.0%, 7/100, respectively), and the differences were statistically significant (χ2=0.001, 0.001, 0.001 and 0.004, all P<0.01). Conclusions Anxiety is associated with CAG and intestinal metaplasia, while depression is associated with intestinal metaplasia. In male patients and patients under 50 years old, depression, negative event and high psychiatric stress are more significantly related to intestinal metaplasia. The mental characteristics of extroversion, emotional instability, psychoticism and concealment are closely associated with CAG. Key words: Chronic gastritis; Atrophy; Intestinal metaplasia; Psychological characteristic; Mental characteristic

Quantitative Diagnosis of Atrophic Gastritis by Probe-Based Confocal Laser Endomicroscopy.

Aims The aims of this study were to characterize nonatrophic and atrophic gastric mucosa under conventional endoscopy and probe-based confocal laser endomicroscopy (pCLE) modes and to define quantitative diagnostic parameters for these lesions under pCLE. Method In phase I, 64 patients with gastric mucosal lesions diagnosed by gastrointestinal endoscopy were enrolled in the study. Normal mucosa and suspicious lesions were evaluated under normal white light imaging (WLI) and pCLE mode. Descriptive characteristic of gastric mucosal inflammation and atrophy under pCLE were defined according to the histology. In phase II, the criteria for nonatrophic gastritis (NAG) and chronic atrophic gastritis (CAG) under pCLE were used to diagnose the mucosal lesions in 431 patients. Diagnostic accuracy of each endoscopy modes was evaluated by measuring the concordance with histology. Result A total of 64 patients with 187 positions were enrolled in the first part of this study. According to the histological diagnosis, the vessel diameter was increased in the NAG (11.18 ± 0.1 μm) and CAG (13.21 ± 0.29 μm) and CAG (13.21 ± 0.29 μm) and CAG (13.21 ± 0.29 μm) and CAG (13.21 ± 0.29 μm) and CAG (13.21 ± 0.29 μm) and CAG (13.21 ± 0.29 μm) and CAG (13.21 ± 0.29 Conclusion pCLE shows high potential for the diagnosis of gastric inflammation and atrophy based on quantitative criteria and has the ability to be a substitute for histology in the diagnosis of diffuse lesions in the stomach.

PGC-MG7 combination could be used as a follow-up panel for monitoring dynamical progression of gastric precancerous diseases.

ObjectiveThe aim of this study was to investigate the value of the combined expression of the gastric mucosal differentiation protein pepsinogen C (PGC) and gastric cancer (GC)-associated antigen MG7 for the diagnosis of GC and prediction of the development from precancerous conditions to GC.MethodsThe gastric mucosal biopsies of 285 subjects enrolled from a region with a high incidence of GC were obtained and histopathologically examined. Subjects testing negative for GC (n=208) were followed up from 1998 to 2015. The levels of PGC and MG7 in the biopsies were determined by immunohistochemistry.ResultsPGC was positive in 91.4% of the non-atrophic gastritis, 26.5% of the atrophic gastritis, and 0% of the GC. MG7 was positive in 15.0% of the non-atrophic gastritis, 82.4% of the atrophic gastritis, and 94.8% of the GC. The non-atrophic gastritis group was predominantly “PGC+MG7−”. The atrophic gastritis and GC groups were predominantly “PGC−MG7+”. The rate of GC in subjects with “PGC−MG7+” staining was 113.4-fold higher [95% confidence interval (95% CI): 15.3−869.4, P<0.001] than that in subjects with other staining patterns. The sensitivity and specificity of the “PGC−MG7+” pattern were 92.2% and 78.8% for the detection of GC and 77.2% and 97.9% for GC and precancerous disease, respectively. In the follow-up cohort of non-GC subjects, the risk of developing GC was higher in those with the “PGC−MG7+” staining pattern.ConclusionsOur data suggest that the “PGC−MG7+” pattern can be employed as a useful follow-up panel for detecting individuals with a high risk of GC, and the dynamic assessment of the follow-up panel needs multi-centre large-scale validation in the future.

Expression and clinical significance of plasma methylated Septin9 gene in patients with gastric cancer

Objective To explore the expression and clinical significance of plasma methylated Septin9 gene (mSEPT9) in patients with gastric cancer. Methods From March to October in 2018, 380 patients visited Xijing Hospital of Digestive Diseases were selected. The patients were divided into gastric cancer (GC) group, atrophic gastritis (AG) group and non-atrophic gastritis (NAG) group. The positive expression rate of plasma circulating mSEPT9 of the three groups were detected by polymerase chain reaction (PCR) fluorescence probe method, its correlation with clinicopathological characteristics of gastric cancer were analyzed and also compared with the positive rate of carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9). Chi-square test and continuity correction chi-square test were performed for statistical analysis. Results The actual number of valid samples was 357 including 147 of GC group, 83 of AG group and 127 of NAG group. The positive rate of plasma mSEPT9 of GC group was higher than those of AG group and NAG group (46.9%, 69/147 vs. 4.8%, 4/83 and 3.9%, 5/127), and the differences were statistically significant (χ2=43.438 and 63.912, both P<0.016). The sensitivity and specificity of plasma mSEPT9 in patients with gastric cancers were 46.9%(69/147) and 95.7%(201/210), respectively. The positive rate of mSEPT9 was higher in gastric cancer patients with tumor maximum diameter over 5.0 cm, intestinal-type gastric cancer in Lauren classification, lymphatic metastasis, vascular and neurological invasion, middle-late stage (stage Ⅲ and Ⅳ) in clinical classification, which were 57.6% (38/66) vs. 35.6% (26/73), 52.6%(51/97) vs. 31.0% (13/42), 53.0% (61/115) vs. 25.0% (8/32), 55.6% (65/117) vs. 13.3% (4/30), 50.8% (65/128) vs. 4/19 and 53.5% (61/114) vs. 24.2% (8/33), respectively; and the differences were statistically significant (χ2=6.728, 5.517, 7.905, 17.091, 5.871 and 8.998, all P<0.05). The positive rate of plasma mSEPT9 in gastric cancer patients was higher than those of CEA and CA19-9 (46.9%, 69/147 vs. 32.0%, 47/147 and 17.7%, 26/147, respectively), and the differences were statistically significant (χ2=6.892 and 17.437, both P<0.016). Conclusions The positive expression of plasma mSEPT9 in gastric cancer patients has not only high sensitivity but good specificity as well, and it is also related to the clinical stage. The detection of this gene may have important clinical significance in non-invasive diagnosis and prognosis evaluation in patients with advanced gastric cancer. Key words: Methylation; Stomach neoplasms; SEPT9; Pathological characteristics; Clinical significance

Significance of Serological Gastric Biopsy in Different Gastric Mucosal Lesions: an Observational Study.

Screening and timely treatment of precancerous gastric cancer diseases or of gastric cancer in the early stages has important significance in reducing the incidence and mortality of gastric cancer. Gastroscopy and histopathological biopsy are still the gold standards for the diagnosis of gastric diseases. But the application of astroscopy for the screening and diagnosis of gastric diseases is limited. In recent years, serum pepsinogen (PG), gastrin, and Helicobacter pylori (H. pylori) IgG antibodies have become indicators for "serological biopsy" of the gastric mucosa. From January 2016 to January 2018, a total of 2,394 patients with digestive tract symptoms underwent gastroscopy. According to the endoscopic examination and pathological diagnosis, there were four case groups: 1,376 cases of chronic non-atrophic gastritis, 708 cases of chronic atrophic gastritis, 265 cases of gastric ulcer, and 45 cases of gastric cancer. Serological gastric biopsies were performed and analyzed. The serum levels of PGI in the chronic atrophic gastritis group was significantly lower than that in the chronic non-atrophic gastritis group, gastric ulcer group, and gastric cancer group (p < 0.05). The serum levels of PGII and G-17 in the gastric cancer group were significantly higher than those in the chronic non-atrophic Gastritis group, chronic atrophic gastritis group, and gastric ulcer group (p < 0.05). The PGR in the gastric cancer group was significantly lower than that in the chronic non-atrophic gastritis group, chronic atrophic Gastritis group, and gastric ulcer group (p < 0.05). The H. pylori positive rates in the chronic atrophic gastritis group and gastric cancer group were higher than those in the chronic non-atrophic gastritis group and gastric ulcer Group (p < 0.05). Serological gastric biopsy is closely correlated to gastric mucosal disease and can be used as a Screening tool in gastric disease.

A multi-center clinical research of diagnostic value of serum gastrin-17 combined with pepsinogen for gastric cancer

Objective To evaluate the diagnostic value of gastrin-17(G-17) and pepsinogen(PG) for gastric cancer. Methods A multicenter cross-sectional study of patients with continuous stomach discomfort from four centers including Changhai Hospital Affiliated to Second Military Medical University, the First Hospital Affiliated to Anhui Medical University, Qinghai Provincial People′s Hospital and the First Hospital Affiliated to Zhejiang University of Chinese Medicine from May 2014 to September 2015 was conducted. Before gastroscopy, fasting serum gatrin-17 and pepsinogen were analyzed by enzyme-linked immunosorbent assay(ELISA). The efficacy of G-17 and PG were evaluated according to endoscopic and pathological results. Results Based on the results of the pathological diagnosis, 1 122 cases were enrolled and divided into chronic atrophic gastritis group(548 cases), chronic non-atrophic gastritis group(370 cases), and gastric cancer group(204 cases). Serum G-17 and PGⅡ levels significantly increased(P 7 pmol/L and PGR 7 pmol/L and PGⅡ>10 μg/L was regarded as the cut-off value, the sensitivity, specificity, accuracy, positive predictive value and negative predictive value were 48.04%, 79.74%, 73.98%, 34.51% and 87.35% respectively. If PGR 10 μg/L was regarded as the cut-off value, the sensitivity, specificity, accuracy, positive predictive value and negative predictive value were 33.82%, 84.86%, 75.58%, 33.17% and 85.23% respectively. Based on logistic regression analysis of the independent variables of high serum G-17 value(>7 pmol/L), low serum PGR value( 10 μg/L), their OR value were 2.592, 2.237 and 1.864 respectively, and high serum G-17 value showed the highest risk of gastric cancer. Conclusion High serum G-17 and PGⅡ, low PGR are indicators of gastric cancer. Combination of G-17 and PGR has the best diagnostic value for gastric cacer. Gastric cancer can be screened in large scale by combining G-17 and PGR in order to improve the early diagnostic rate of gastric cancer and reduce the mortality of gastric cancer in our country. Key words: Stomach neoplasms; Diagnosis; Multicenter study; Pepsinogens; Gastrin-17

A novel approach for the detection of early gastric cancer: Fluorescence spectroscopy of gastric juice

This study aimed to investigate the efficacy of fluorescence spectroscopy of gastric juice for early gastric cancer (EGC) screening. Gastric juice was collected from 101 participants who underwent endoscopy in the Outpatient Endoscopy Center of Peking University Third Hospital. The participants were divided into three groups: the normal mucosa or chronic non-atrophic gastritis (NM-CNAG) group (n = 35), advanced gastric cancer (AGC) group (n = 33) and EGC group (n = 33). Fluorescence spectroscopic analysis was performed in all the gastric juice samples and the maximum fluorescence intensity of the first peak (P1 FI) was measured. The mean fluorescence intensity of P1 FI of gastric juice in AGC (92.1 ± 10.7) and EGC (90.8 ± 12.0) groups was significantly higher than that in the NM-CNAG group (55.7 ± 7.5) (AGC vs NM-CNAG, P = 0.006 and EGC vs NM-CNAG, P = 0.015, respectively). The areas under the receiver operating characteristic curves for the detection of AGC and EGC were 0.681 (95% confidence interval [CI] 0.553-0.810, P = 0.010) and 0.655 (95% CI 0.522-0.787, P = 0.028). With the P1 FI of ≥47.7, the sensitivity, specificity and accuracy for detecting EGC were 69.7%, 57.1% and 63.2%, respectively. The enhancement of P1 FI of gastric juice occurs at the early stage of gastric cancer. Fluorescence spectroscopy of gastric juice may be used as a novel screening tool for the early detection of gastric cancer.

Mannan-binding lectin B allele is associated with a risk of developing more severe gastric mucosal atrophy in Helicobacter pylori-infected Japanese patients

Mannan-binding lectin (MBL) is an important constituent of the innate immune system, and deficiency of MBL has been reported to increase the overall susceptibility of an individual to infectious disease. Codon 54 G/A variant of exon 1 (B allele) affects MBL2 gene and alters its activity. We investigated the influence of MBL2 variant on the risk of gastroduodenal diseases and on the severity of Helicobacter pylori-induced gastritis in a Japanese population. One hundred and two gastric ulcers, 48 duodenal ulcers, 275 nonulcer participants were included in this study. B allele of the MBL2 gene was detected by polymerase chain reaction based restriction fragment length polymorphism. The severity of the histological chronic gastritis in antral biopsy specimens were classified according to the updated Sydney system. MBL2 B allele was significantly associated with severity of gastric mucosal atrophy and intestinal metaplasia (atrophy, G/G vs. G/A vs. A/A; P=0.02, A/A vs. others; P=0.009, intestinal metaplasia; G/G vs. G/A vs. A/A; P=0.03, A/A vs. others; P=0.004). When participants were divided into the following three groups according to the severity of gastric atrophy: the nonatrophic gastritis (NA) group, the severe atrophic gastritis (SA) group, and mild atrophic gastritis (MA) group, the frequency of A/A was significantly higher in the SA group than in others (SA vs. MA; odds ratio=8.42, 95% confidence interval=1.05-67.45, SA vs. others; odds ratio=10.06, 95% confidence interval=1.26-80.45). Our data suggest that the MBL2 codon 54 B allele is associated with a risk of developing more severe gastric mucosal atrophy in H. pylori-infected Japanese patients.

Clinical Utility of Serum Pepsinogen Levels as a Screening Test of Atrophic Gastritis

Atrophic gastritis is a well known risk factor for gastric adenocarcinoma. Its confirmatory diagnosis requires histology via endoscopy, which is an invasive method; therefore, periodic follow up evaluation as a screening method is difficult to perform. We evaluated the clinical utility of serum pepsinogens (PG) as a biomarker for screening of atrophic gastritis. The study population consisted of 130 selected dyspeptic patients (M:F=52:78; age, 16-105 yrs; mean age, 50.8 yrs) who had undergone a diagnostic endoscopy. The serum pepsinogen test was performed by a latex turbidimetric immunoassay method (HBI, Korea) using Toshiba-200FR automatic analyzer. The PGI, II level and PGI:PGII ratio of non-atrophic gastritis group were compared with those of atrophic gastritis group, and a correlation with Helicobacter pylori infection was examined. Cut-off points for screening of atrophic gastritis were determined. The mean serum concentration of PGI showed a decline from normal (60.7 ng/mL), nonatrophic gastritis (54.2 ng/mL), and atrophic gastritis (51.8 ng/mL) to gastric adenocarcinoma (32.6 ng/mL). The mean ratio of PGI:PGII was lower in atrophic gastritis (3.2) compared to non-atrophic gastritis (4.7) (P=0.021). In patients with H. pylori infection, the mean serum PGII level was higher and the PGI:PGII ratio was lower than those in patients without H. pylori infection, and the differences were statistically significant. For screening of atrophic gastritis, the best cut-off point of PGI:PGII ratio was 4, with a sensitivity of 82.6% and specificity of 91.7%. The serum pepsinogen test is a useful biomarker for screening of atrophic gastritis, a well-known precancerous lesion of gastric adenocarcinoma. Measuring both pepsinogen I and II concentrations simultaneously to obtain pepsinogen I/II ratio provides a clinically useful information for the detection of atrophic gastritis.

Diversity of Helicobacter pylori cagA and vacA Genes in Costa Rica: Its Relationship with Atrophic Gastritis and Gastric Cancer

Associations between Helicobacter pylori gene diversity and gastric cancer have not been reported on in Costa Rica, despite its being one of the countries with the highest gastric cancer incidence and mortality rates in the world. The aim of this study was to determine the prevalence of H. pylori cagA and vacA genes and investigate whether it could be correlated with atrophic gastritis (AG) and gastric cancer (GC) in Costa Rica. Genomic DNAs from isolates of 104 patients classified into two groups: non-atrophic gastritis group (n = 68) and atrophic gastritis group (n = 36), were subjected to PCR-based genotyping of cagA and vacA genes and their correlation with clinical outcome was investigated. Total DNA extractions from gastric tissues of 25 H. pylori-infected gastric cancer patients were utilized for comparative purposes. The presence of cagA (75.3%), vacA s1b (75.3%), and vacA m1 (74.2%) was detected, and colonization by strains with different vacA genotypes in the same stomach was found in 9.7% of the patients. Age- and sex-adjusted vacA s1b and vacA m1 were associated with GC while only vacA m1 was significantly associated with AG. A tendency for association between cagA and vacA s1b, and AG was reported. The prevalence status of the cagA and vacA (s1/m1) genes in Costa Rica seems to fall between that found in European/North American and East Asian countries, and both cagA and vacA seem to have clinical relevance in this country.

Factors affecting the serum gastrin 17 level: an evidence‐based analysis of 3906 serum samples among Chinese

To investigate the influence of gender, age, site of lesion, disease type and Helicobacter pylori (H. pylori) infection on the human serum gastrin-17 level and to study the diagnostic value of serum gastrin-17 in gastric precancerous lesions and gastric cancer. Serum gastrin-17 and serum H. pylori IgG antibody were detected by the ELISA method. The different gastric disease groups were confirmed by endoscopy and histopathology. Among the 3906 serum samples according to the gender, age, site of lesion and the data of different gastric disease groups, the serum gastrin-17 level was markedly higher in people>or=60 years old than that in younger age groups. The serum gastrin-17 level increased progressively in the following order: healthy control group, nonatrophic gastritis group, gastric ulcer group, and the serum gastrin-17 level was higher in the atrophic gastritis with dysplasia group than that without it, the lowest level being in the gastric cancer group. Among the 2946 serum samples matched with the site of the lesion, the serum gastrin-17 level was higher in those with antral diseases than in those with gastric corpus diseases. Among the 3805 serum samples matched with the H. pylori infection data, the serum gastrin-17 level was higher in the H. pylori-positive group than in the H. pylori-negative group. In people over 60 years of age, the serum gastrin-17 level tends to increase. In subjects with precancerous gastric lesions, it may increase significantly with the progression of gastric disease, and ultimately decrease in gastric cancer. Serum gastrin-17 is a good biomarker to differentiate benign from malignant gastric diseases. The site of the gastric lesions is an important factor affecting the serum gastrin-17 level, whereas H. pylori infection is usually associated with its increment.