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Gut Sep 2019To develop a gastric cancer (GC) risk prediction rule as an initial prescreening tool to identify individuals with a high risk prior to gastroscopy.
OBJECTIVE
To develop a gastric cancer (GC) risk prediction rule as an initial prescreening tool to identify individuals with a high risk prior to gastroscopy.
DESIGN
This was a nationwide multicentre cross-sectional study. Individuals aged 40-80 years who went to hospitals for a GC screening gastroscopy were recruited. Serum pepsinogen (PG) I, PG II, gastrin-17 (G-17) and anti- IgG antibody concentrations were tested prior to endoscopy. Eligible participants (n=14 929) were randomly assigned into the derivation and validation cohorts, with a ratio of 2:1. Risk factors for GC were identified by univariate and multivariate analyses and an optimal prediction rule was then settled.
RESULTS
The novel GC risk prediction rule comprised seven variables (age, sex, PG I/II ratio, G-17 level, infection, pickled food and fried food), with scores ranging from 0 to 25. The observed prevalence rates of GC in the derivation cohort at low-risk (≤11), medium-risk (12-16) or high-risk (17-25) group were 1.2%, 4.4% and 12.3%, respectively (p<0.001).When gastroscopy was used for individuals with medium risk and high risk, 70.8% of total GC cases and 70.3% of early GC cases were detected. While endoscopy requirements could be reduced by 66.7% according to the low-risk proportion. The prediction rule owns a good discrimination, with an area under curve of 0.76, or calibration (p<0.001).
CONCLUSIONS
The developed and validated prediction rule showed good performance on identifying individuals at a higher risk in a Chinese high-risk population. Future studies are needed to validate its efficacy in a larger population.
Topics: Adult; Aged; Aged, 80 and over; Antibodies, Bacterial; Biomarkers, Tumor; Diet; Early Detection of Cancer; Female; Gastrins; Gastroscopy; Helicobacter Infections; Helicobacter pylori; Humans; Male; Mass Screening; Middle Aged; Pepsinogen A; Pepsinogen C; Predictive Value of Tests; Random Allocation; Reproducibility of Results; Risk Factors; Secondary Prevention; Stomach Neoplasms
PubMed: 30926654
DOI: 10.1136/gutjnl-2018-317556 -
The Journal of General Physiology Mar 1962Evidence relating to the structure and properties of swine pepsinogen and pepsin has been reviewed and used to suggest a tentative two dimensional picture of the...
Evidence relating to the structure and properties of swine pepsinogen and pepsin has been reviewed and used to suggest a tentative two dimensional picture of the skeleton of these two proteins. When pepsinogen, a folded single peptide chain, is converted to pepsin, there is a profound change in the physical and chemical properties of the protein. In an as yet unknown manner, except that it is initiated by a peptic cleavage of the protein chain, a single enzymic site is formed. This site is made up, quite probably, of the secondary carboxyl group of glutamic acid or of aspartic acid and a tyrosine phenol group in close proximity so that they can form hydrogen or hydrophobic bonds with the substrate in some unique manner that permits hydrolysis to occur at an accelerated rate.
Topics: Animals; Hydrogen-Ion Concentration; Hydrolysis; Pepsin A; Pepsinogen A; Pepsinogens; Swine; Tyrosine
PubMed: 13906833
DOI: No ID Found -
The Turkish Journal of Gastroenterology... Mar 2022Serum pepsinogen, a useful indicator of gastric acidity, could reflect small intestinal bacterial overgrowth. The aim of this study is to evaluate the relationship...
BACKGROUND
Serum pepsinogen, a useful indicator of gastric acidity, could reflect small intestinal bacterial overgrowth. The aim of this study is to evaluate the relationship between small intestinal bacterial overgrowth and profiles including pepsinogen or gastrin.
METHODS
We conducted a prospective study with 62 patients with a functional gastrointestinal disorder. All patients underwent glucose breath test for small intestinal bacterial overgrowth, immediately followed by upper endoscopy to survey gastric injury and Campylobacter-like organism test for Helicobacter pylori and serum laboratory tests including gastrin, pepsinogen I and II.
RESULTS
The positivity to small intestinal bacterial overgrowth was 17.7%. Significantly, low total hydrogen concentration during a glucose breath test, low prevalence for gastric injury, and high H. pylori positivity rate were shown in groups with pepsinogen I/II ratio ≤ 3.5 compared to those with pepsinogen I/II ratio > 3.5 or in groups with serum gastrin > 35.4 pg/mL comparing to those with serum ≤ 35.4 pg/mL, respectively. A high gastrin level was independently associated with H. pylori infection. A proportionally correlated tendency between pepsinogen I/II ratio and total hydrogen concentration was shown, whereas that of inverse proportion between H2 and gastrin was observed. Old age was solely independent predicting factor for small intestinal bacterial overgrowth (P = .03) in the multivariate analysis.
CONCLUSION
Old age was significantly related to the presence of small intestinal bacterial overgrowth in functional gastrointestinal disorder patients. Although pepsinogen and small intestinal bacterial overgrowth seem irrelevant, elevated gastrin level may cautiously indicate a decreased breath hydrogen concentration. Further studies should consider the function of intestinal motility and gastric acidity in patients with hydrogen-producing small intestinal bacterial overgrowth.
Topics: Biomarkers; Gastrins; Glucose; Helicobacter Infections; Helicobacter pylori; Humans; Hydrogen; Pepsinogen A; Pepsinogen C; Prospective Studies
PubMed: 35410855
DOI: 10.5152/tjg.2021.201145 -
The Korean Journal of Internal Medicine Sep 2016Endoscopic findings of the background gastric mucosa are important in the Helicobacter pylori-seroprevalent population. It is strongly correlated not only with the risk... (Review)
Review
Endoscopic findings of the background gastric mucosa are important in the Helicobacter pylori-seroprevalent population. It is strongly correlated not only with the risk of gastric cancer, but also with the excretion ability of gastric mucosa cells. In noninfected subjects, common endoscopic findings are regular arrangement of collecting venules, chronic superficial gastritis, and erosive gastritis. In cases of active H. pylori infection, nodularity on the antrum, hemorrhagic spots on the fundus, and thickened gastric folds are common endoscopic findings. The secreting ability of the gastric mucosa cells is usually intact in both noninfected and actively infected stomachs, and the intragastric condition becomes hyperacidic upon inflammation. Increased serum pepsinogen II concentration correlates well with active H. pylori infection, and also indicates an increased risk of diffuse-type gastric cancer. In chronic inactive H. pylori infection, metaplastic gastritis and atrophic gastritis extending from the antrum (closed-type chronic atrophic gastritis) toward the corpus (open-type chronic atrophic gastritis) are common endoscopic findings. The intragastric environment is hypoacidic and the risk of intestinal-type gastric cancer is increased in such conditions. Furthermore, there is a decrease in serum pepsinogen I concentration when the secreting ability of the gastric mucosa cells is damaged. Serologic and endoscopic changes that occur upon H. pylori infection are important findings for estimating the secreting ability of the gastric mucosa cells, and could be applied for the secondary prevention of gastric cancer.
Topics: Gastric Mucosa; Gastritis; Gastroscopy; Helicobacter Infections; Helicobacter pylori; Humans; Pepsinogen A; Risk Factors; Stomach Neoplasms
PubMed: 27604795
DOI: 10.3904/kjim.2016.166 -
Nutrition, Metabolism, and... Jan 2021Serum pepsinogens (PGs) are biomarkers for gastric mucosal damage and have been reported to be associated with atherosclerosis. Its correlation with atherosclerotic... (Observational Study)
Observational Study
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.
Topics: Aged; Atherosclerosis; Biomarkers; Cross-Sectional Studies; Female; Humans; Male; Middle Aged; Pepsinogen A; Pepsinogen C; Retrospective Studies
PubMed: 33127250
DOI: 10.1016/j.numecd.2020.07.045 -
Journal of the Formosan Medical... Jun 2021Very few studies have explored the changes of serum pepsinogen after bariatric surgery and no research has evaluated the feasibility of ABC classification to predict...
BACKGROUND
Very few studies have explored the changes of serum pepsinogen after bariatric surgery and no research has evaluated the feasibility of ABC classification to predict gastric cancer risk after bariatric surgery.
METHODS
We enrolled 94 obese subjects that received bariatric surgery, including 41 sleeve gastrectomy (SG) and 53 Roux-en-Y gastric bypass (RYGB). The serum pepsinogen I (PGI), pepsinogen II (PGII), PGI/II ratio and seropositivity of Helicobacter pylori ( H. pylori ) were measured before and one year after surgery. Patients were classified according to ABC classification and post-operative change was evaluated.
RESULTS
Preoperatively, four (4.2%) patients were classified into high risk group (classification C and D) for gastric cancer. Significant reduction of PGI, PGII and decrease of PGI/II ratio were noted after bariatric surgery. H. pylori seropositive patients had a greater postoperative change of PGI (-38.6μg/L vs -22.1μg/L, p=0.003) and PGII (-8.0μg/L vs -2.5μg/L, p <0.001) but a less postoperative change of PGI/II ratio (-0.6 vs -2.1, p =0.04) than H. pylori seronegative patients. One year after surgery, the portion of high risk group of ABC classification for gastric cancer increased markedly from 4.2% to 23.7%.
CONCLUSION
Both of SG and RYGB resulted in significant reduction of serum PGI and PGII after bariatric surgery, and significantly influenced the ABC classification. The application of ABC classification for gastric cancer screening was limited after bariatric surgery.
Topics: Bariatric Surgery; Helicobacter Infections; Helicobacter pylori; Humans; Pepsinogen A; Pepsinogen C
PubMed: 33199102
DOI: 10.1016/j.jfma.2020.10.029 -
Scientific Reports Mar 2022Simple objective modalities are required for evaluating suspected autoimmune gastritis (AIG). This cross-sectional study aimed to examine whether pepsinogen, gastrin,...
Simple objective modalities are required for evaluating suspected autoimmune gastritis (AIG). This cross-sectional study aimed to examine whether pepsinogen, gastrin, and endoscopic findings can predict AIG. The diagnostic performance of endoscopic findings and serology in distinguishing AIG was evaluated. AIG was diagnosed in patients (N = 31) with anti-parietal cell antibody and/or intrinsic factor antibody positivity and histological findings consistent with AIG. Non-AIG patients (N = 301) were seronegative for anti-parietal cell antibodies. Receiver operating characteristic curve analysis of the entire cohort (N = 332) identified an endoscopic atrophic grade cutoff point of O3 on the Kimura-Takemoto classification (area under the curve [AUC]: 0.909), while those of pepsinogen-I, I/II ratio, and gastrin were 20.1 ng/mL (AUC: 0.932), 1.8 (AUC: 0.913), and 355 pg/mL (AUC: 0.912), respectively. In severe atrophy cases (≥ O3, N = 58, AIG/control; 27/31), the cutoff values of pepsinogen-I, I/II ratio, and gastrin were 9.8 ng/mL (AUC: 0.895), 1.8 (AUC: 0.86), and 355 pg/mL (AUC: 0.897), respectively. In conclusion, endoscopic atrophy is a predictor of AIG. High serum gastrin and low pepsinogen-I and I/II ratio are predictors even in the case of severe atrophy, suggesting their usefulness when the diagnosis of AIG is difficult or as serological screening tests.
Topics: Atrophy; Autoantibodies; Autoimmune Diseases; Cross-Sectional Studies; Gastrins; Gastritis, Atrophic; Helicobacter Infections; Humans; Pepsinogen A
PubMed: 35273265
DOI: 10.1038/s41598-022-07947-1 -
Internal Medicine (Tokyo, Japan) 2007Since the 1990's, the test for serum pepsinogen as a marker for chronic atrophic gastritis has been incorporated into gastric cancer screening programs, on a trial... (Review)
Review
Since the 1990's, the test for serum pepsinogen as a marker for chronic atrophic gastritis has been incorporated into gastric cancer screening programs, on a trial basis, to identify people at high risk for gastric cancer. The addition of the serum test to the cancer screening program has been shown to improve the detection rate of cancer and pepsinogen testing is useful in detecting early-stage gastric cancers arising from atrophic gastric mucosa, which macroscopically tend to be elevated and histologically differentiated. Furthermore, the cost for the detection of a single cancer case is much less than that for conventional screening. Thus, with the introduction of pepsinogen testing, complimenting barium X-ray, a more efficient screening system is available.
Topics: Adult; Barium Radioisotopes; Biomarkers; Endoscopy, Gastrointestinal; Humans; Incidence; Japan; Male; Mass Screening; Middle Aged; Pepsinogen A; Radiographic Image Enhancement; Risk Assessment; Sensitivity and Specificity; Stomach Neoplasms
PubMed: 17379991
DOI: 10.2169/internalmedicine.46.6181 -
Archives of Medical Research Feb 2023Gastric cancer (GC) is often diagnosed at an advanced stage and thus patients have a poor prognosis. This implies that early detection of this cancer will improve... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Gastric cancer (GC) is often diagnosed at an advanced stage and thus patients have a poor prognosis. This implies that early detection of this cancer will improve patient prognosis and survival. This systematic review explored the association of circulating protein and metabolite biomarkers with GC development.
METHODS
A literature search was conducted until November 2021 on Medline, Embase, Cochrane library, and Web of Science databases. Studies were included if they assessed circulating proteins and metabolites in blood, urine, or saliva and determined their association with GC risk. Quality of identified studies was determined using the Newcastle-Ottawa scale for cohort studies. Random and fixed effects meta-analyses were performed to calculate pooled odds ratio.
RESULTS
A total of 53 studies were included. High levels of anti-Helicobacter pylORi IgG levels, pepsinogen I (PGI) <30 µg/L and serum pepsinogen I/ pepsinogen II (PGI/II) ratio<3 were positively associated with risk of developing GC (pooled odds ratio (OR): 2.70; 95% CI: 1.44-5.04, 5.96, 95% CI: 2.65-13.42 and 4.43; 95% CI: 3.04-6.47). In addition, an inverse relationship was found between ferritin, iron and transferrin levels and risk of developing GC (OR: 0.62; 95% CI: 0.38-1,0.97; 95% CI: 0.94-1 and 0.85; 95% CI: 0.76-0.94). However, there was no association between levels of glucose, cholesterol, vitamin C, vitamin B12, vitamin A, α-Carotene, β-Carotene, α-Tocopherol, γ-Tocopherol, and GC risk.
CONCLUSION
The pooled analysis demonstrated that high levels of anti-Helicobacter pylORi IgG, PGI<30µg/L and serum PGI/II ratio <3 and low levels of ferritin, iron and transferrin were associated with risk of GC.
Topics: Humans; Stomach Neoplasms; Pepsinogen A; Biomarkers; Pepsinogen C; Immunoglobulin G; Ferritins; Iron; Transferrins; Helicobacter Infections
PubMed: 36759293
DOI: 10.1016/j.arcmed.2022.12.012 -
Frontiers in Cellular and Infection... 2022Association of gastric atrophy or cancer with levels of serum pepsinogens, gastrin-17 and anti- IgG antibody have been extensively studied. However, the association of...
BACKGROUND
Association of gastric atrophy or cancer with levels of serum pepsinogens, gastrin-17 and anti- IgG antibody have been extensively studied. However, the association of serum pepsinogen and gastrin-17 with infection has not been studied in a large population.
AIM
To investigate the impact of infection on serum levels of pepsinogens and gastrin-17.
METHODS
A total of 354, 972 subjects who underwent health check-ups were included. Serum levels of pepsinogens and gastrin-17 were measured using the enzyme-linked immunosorbent assay infection was detected using C-urea breath test (UBT). Multivariable logistic regression analysis was used to investigate the association of serum pepsinogen and gastrin-17 with infection.
RESULTS
prevalence was 33.18% in this study. The mean levels of pepsinogens and gastrin-17 were higher, while the mean pepsinogen-I/II ratio were lower among -positive than -negative subjects. In -positive subjects, pepsinogen and gastrin-17 levels correlated positively, whereas the pepsinogen-I/II ratio correlated negatively with UBT values (e.g., the mean serum level of pepsinogen-I in subjects with UBT values in the range of 100-499dpm, 500-1499dpm, and ≥1500dpm was 94.77 ± 38.99, 102.77 ± 43.59, and 111.53 ± 47.47 ng/mL, respectively). Compared with -negative subjects, the adjusted odds ratio (aOR) of having pepsinogen-I ≤ 70 ng/mL in the three -positive but with different UBT value groups was 0.31 (<0.001), 0.16 (<0.001), and 0.08 (<0.001), respectively; while the aOR of having G-17>5.70 pmol/L was 4.56 (<0.001), 7.43 (<0.001), and 7.12 (<0.001). This suggested that -positive subjects with higher UBT values were less likely to have pepsinogen-I ≤70 ng/mL (a serum marker for gastric atrophy), but more likely to have gastrin-17 >5.70 pmol/L (a marker for peptic ulcer).
CONCLUSIONS
-positive subjects with higher UBT values are unlikely to have gastric atrophy, but may have greater risk of severe gastritis or peptic ulcers. Our study suggests that -positive patients with high UBT values may benefit the most from eradication.
Topics: Atrophy; Biomarkers; Breath Tests; Gastrins; Gastritis, Atrophic; Helicobacter Infections; Helicobacter pylori; Humans; Pepsinogen A; Urea
PubMed: 36051244
DOI: 10.3389/fcimb.2022.980399