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World Journal of Gastroenterology Oct 2014Gastric cancer continues to be an important healthcare problem from a global perspective. Most of the cases in the Western world are diagnosed at late stages when the... (Review)
Review
Gastric cancer continues to be an important healthcare problem from a global perspective. Most of the cases in the Western world are diagnosed at late stages when the treatment is largely ineffective. Helicobacter pylori (H. pylori) infection is a well-established carcinogen for gastric cancer. While lifestyle factors are important, the efficacy of interventions in their modification, as in the use of antioxidant supplements, is unconvincing. No organized screening programs can be found outside Asia (Japan and South Korea). Although several screening approaches have been proposed, including indirect atrophy detection by measuring pepsinogen in the circulation, none of them have so far been implemented, and more study data is required to justify any implementation. Mass eradication of H. pylori in high-risk areas tends to be cost-effective, but its adverse effects and resistance remain a concern. Searches for new screening biomarkers, including microRNA and cancer-autoantibody panels, as well as detection of volatile organic compounds in the breath, are in progress. Endoscopy with a proper biopsy follow-up remains the standard for early detection of cancer and related premalignant lesions. At the same time, new advanced high-resolution endoscopic technologies are showing promising results with respect to diagnosing mucosal lesions visually and targeting each biopsy. New histological risk stratifications (classifications), including OLGA and OLGIM, have recently been developed. This review addresses the current means for gastric cancer primary and secondary prevention, the available and emerging methods for screening, and new developments in endoscopic detection of early lesions of the stomach.
Topics: Biopsy; Early Detection of Cancer; Gastroscopy; Humans; Life Style; Neoplasm Staging; Precancerous Conditions; Predictive Value of Tests; Preventive Health Services; Risk Assessment; Risk Factors; Risk Reduction Behavior; Stomach Neoplasms
PubMed: 25320521
DOI: 10.3748/wjg.v20.i38.13842 -
Acta Bio-medica : Atenei Parmensis Jul 2020Dyspepsia is a functional GI disorder consisting in a wide range of symptoms. The main diagnostic challenge has been whether to perform an EGD or an abdominal US in...
Dyspepsia is a functional GI disorder consisting in a wide range of symptoms. The main diagnostic challenge has been whether to perform an EGD or an abdominal US in order not to miss organic lesions, but to avoid unnecessary and sometimes invasive tests. Pepsinogen serology has been proposed as an useful non-invasive test to explore the status of the gastric mucosa, suggesting this strategy as an adequate approach in management of dyspepsia. In a primary care setting, 266 dyspeptic patients were investigated to establish the proper diagnosis. The workup included upper GI endoscopy with biopsies, a structured questionnaire including type and severity of symptoms, serological determination of serum pepsinogens, gastrin 17 and IgG against Hp. Inclusion criteria were dyspeptic symptoms (epigastric pain, nausea and/or vomiting, post prandial fullness, early satiation) lasting more than 1 year and the association between symptoms and food ingestion.. Helicobacter pylori infection was present in 114 subjects, characterized by high levels of pepsinogen II and IgG against Hp. Twenty subjects were classified according with the diagnosis of chronic body atrophic gastritis. Nausea and post prandial fullness were the most frequent symptoms (48% and 41%, respectively) in the studied population, followed by epigastric pain and early satiation (37% and 26% respectively). A diagnosis of normality by serological diagnosis was found in half of patients experiencing epigastric pain and in about 60% of subjects with the three other symptoms (nausea, post prandial fullness, and early satiation). In conclusion, this experience confirms the clinical usefulness of serology in dyspepsia, contributing to correctly diagnosing CAG and H.p. infection in such patients and providing a good correlation with the clinical picture.
Topics: Adult; Aged; Dyspepsia; Female; Humans; Male; Middle Aged
PubMed: 32921764
DOI: 10.23750/abm.v91i3.10150 -
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 -
Clinical Chemistry Oct 2023Autoimmune atrophic gastritis (AAG) is a persistent, corpus-restricted immune-mediated destruction of the gastric corpus oxyntic mucosa with reduced gastric acid and... (Review)
Review
BACKGROUND
Autoimmune atrophic gastritis (AAG) is a persistent, corpus-restricted immune-mediated destruction of the gastric corpus oxyntic mucosa with reduced gastric acid and intrinsic factor secretion, leading to iron deficiency and pernicious anemia as a consequence of iron and cobalamin malabsorption. Positivity toward parietal cell (PCA) and intrinsic factor (IFA) autoantibodies is very common. AAG may remain asymptomatic for many years, thus making its diagnosis complex and often delayed. Due to the increased risk of gastric neoplasms, a timely diagnosis of AAG is clinically important.
CONTENT
The gold standard for AAG diagnosis is histopathological assessment of gastric biopsies obtained during gastroscopy, but noninvasive, preendoscopic serological screening may be useful in some clinical scenarios. Serum biomarkers for AAG may be divided into 2 groups: gastric autoimmunity-related biomarkers, such as PCA and IFA, and gastric corpus atrophy/reduced gastric acid secretion-related biomarkers, such as serum gastrin and pepsinogens. The present review focuses on the clinical significance and pitfalls of serum biomarkers related to gastric autoimmunity and gastric corpus atrophy, including some discussion of analytical methods.
SUMMARY
Serum assays for PCA, IFA, gastrin, and pepsinogen I show good diagnostic accuracy for noninvasive diagnostic work-up of AAG. Diagnostic performance may increase by combining >1 of these tests, overcoming the problem of seronegative AAG. However, appropriately designed, comparative studies with well-characterized patient cohorts are needed to better define the reliability of these biomarkers in the diagnosis of patients with AAG. Currently, positive serum tests should always be followed by the state-of-art diagnostic test, that is, histopathological assessment of gastric biopsies obtained during gastroscopy to definitively confirm or rule out AAG and eventually neoplastic complications.
Topics: Humans; Gastritis, Atrophic; Gastrins; Intrinsic Factor; Reproducibility of Results; Atrophy; Biomarkers; Helicobacter pylori
PubMed: 37680186
DOI: 10.1093/clinchem/hvad082 -
Current Issues in Molecular Biology Jun 2023Recent studies have advanced our understanding of the pathophysiology of autoimmune gastritis, particularly its molecular aspects. The most noteworthy recent advancement... (Review)
Review
Recent studies have advanced our understanding of the pathophysiology of autoimmune gastritis, particularly its molecular aspects. The most noteworthy recent advancement lies in the identification of several candidate genes implicated in the pathogenesis of pernicious anemia through genome-wide association studies. These genes include , , , and . Recent studies have also directed attention towards other genes such as , , , , , and polymorphism. In-depth investigations have been conducted on lymphocytes and cytokines, including T helper 17 cells, interleukin (IL)-17A, IL-17E, IL-17F, IL-21, IL-19, tumor necrosis factor-α, IL-15, transforming growth factor-β1, IL-13, and diminished levels of IL-27. Animal studies have explored the involvement of roseolovirus and in relation to the onset of the disease and the process of carcinogenesis, respectively. Recent studies have comprehensively examined the involvement of autoantibodies, serum pepsinogen, and esophagogastroduodenoscopy in the diagnosis of autoimmune gastritis. The current focus lies on individuals demonstrating atypical presentations of the disease, including those diagnosed in childhood, those yielding negative results for autoantibodies, and those lacking the typical endoscopic characteristics of mucosal atrophy. Here, we discuss the recent developments in this field, focusing on genetic predisposition, epigenetic modifications, lymphocytes, cytokines, oxidative stress, infectious agents, proteins, microRNAs, autoantibodies, serum pepsinogen, gastrin, esophagogastroduodenoscopy and microscopic findings, and the risk of gastric neoplasm.
PubMed: 37504250
DOI: 10.3390/cimb45070334 -
BMC Cancer Jun 2023Pepsinogen C (PGC) is expressed in chief cells, fundic mucous neck cells, and pyloric gland cells of gastric epithelium and also in breast, prostate, lung, and seminal...
BACKGROUND
Pepsinogen C (PGC) is expressed in chief cells, fundic mucous neck cells, and pyloric gland cells of gastric epithelium and also in breast, prostate, lung, and seminal vesicles.
METHODS
We explored the clinicopathological and prognostic significances of PGC mRNA using pathological and bioinformatics analyses. We generated PGC knockout and PGC-cre transgenic mice to observe the effects of PGC deletion and PTEN abrogation in PGC-positive cells on gastric carcinogenesis. Finally, we observed the effects of altered PGC expression on aggressive phenotypes by CCK8, Annexin V staining, wound healing and transwell assays and analyzed the partner proteins of PGC using co-IP (co-immunoprecipitation) and double fluorescence staining.
RESULTS
PGC mRNA level was inversely correlated with the T and G stage and a short survival of gastric cancer (p < 0.05). PGC protein expression was negatively linked to lymph node metastasis, dedifferentiation, and low Her-2 expression of gastric cancer (p < 0.05). No difference in body weight or length was evident between wild-type (WT) and PGC knockout (KO) mice (p > 0.05), but PGC KO mice had a shorter survival than WT mice (p < 0.05). No gastric lesions were observed in the mucosa of the granular stomach in PGC KO mice, which displayed lower frequency and severity of gastric lesion than in WT mice after treated with MNU. Transgenic PGC-cre mice showed high cre expression and activity in the lung, stomach, kidney, and breast. Gastric cancer and triple-negative lobular breast adenocarcinoma were found in PGC-cre/PTEN mice with two previous pregnancies and breast feeding, but breast cancer was not seen in transgenic mice exposed to either estrogen or progesterone, or those with two previous pregnancies and no breast feeding. PGC suppressed proliferation, migration, invasion, and induced apoptosis, and interacted with CCNT1, CNDP2 and CTSB.
CONCLUSION
PGC downregulation was seen in gastric cancer, but PGC deletion resulted in resistance to chemically-induced gastric carcinogenesis. PGC expression suppressed the proliferation and invasion of gastric cancer cells possibly by interacting with CCNT1, CNDP2 and CTSB. Spontaneous triple-negative lobular adenocarcinoma and gastric cancer were seen in PGC-cre/PTEN mice, and the breast carcinogenesis was closely linked to pregnancy and breast feeding, but not to single exposure to estrogen or progesterone, or pregnancy. Limiting either pregnancy or breast feeding might help to prevent hereditary breast cancer.
Topics: Male; Pregnancy; Female; Mice; Animals; Stomach Neoplasms; Pepsinogen C; Progesterone; Carcinogenesis; Gastric Mucosa; Mice, Transgenic; Mice, Knockout; Adenocarcinoma; Estrogens; RNA, Messenger; Transgenes
PubMed: 37291517
DOI: 10.1186/s12885-023-11020-z -
World Journal of Gastrointestinal... Jul 2023Pepsinogen, secreted from the gastric mucosa, is the precursor of pepsin. It is categorized as pepsinogen 1 and pepsinogen 2 based on its immunogenicity. The pepsinogen... (Review)
Review
Pepsinogen, secreted from the gastric mucosa, is the precursor of pepsin. It is categorized as pepsinogen 1 and pepsinogen 2 based on its immunogenicity. The pepsinogen content that can enter the blood circulation through the capillaries of the gastric mucosa is approximately 1% and remains stable all the time. The pepsinogen content in serum will change with the pathological changes of gastric mucosa. Therefore, the level of pepsinogen in serum can play a role in serologic biopsy to reflect the function and morphology of different regions of gastric mucosa and serve as an indicator of gastric disease. This study conducts relevant research on serum pepsinogen 1, pepsinogen 2, and the ratio of pepsinogen 1 to pepsinogen 2, and reviews their important value in clinical diagnosis of infection, gastric ulcer, and even gastric carcinoma, providing ideas for other researchers.
PubMed: 37546552
DOI: 10.4251/wjgo.v15.i7.1174 -
Archives of Iranian Medicine Jul 2014Gastric cancer is a heterogeneous disorder; genetic factors, H. pylori infection and various environmental factors contribute to its development. Advanced atrophic... (Review)
Review
Gastric cancer is a heterogeneous disorder; genetic factors, H. pylori infection and various environmental factors contribute to its development. Advanced atrophic corpus-predominant gastritis provides the histological base for its genesis. Low socio-economic status and poor hygienic conditions, smoking habits, heavy alcohol consumption, high salt and low intake of vegetables and fruits are important external factors for the occurrence of gastric cancer. For its prevention, the eradication of H. pylori infection at an early age is mandatory for subjects at high risk or those living in areas with high prevalence of gastric cancer. Given that an increased serum level of Pepsinogen II is a good biomarker for the presence of gastritis, it seems reasonable to screen all infected subjects at risk of gastric cancer with increased serum pepsinogen II at an early age (at around 30 years) to eradicate H. pylori. An endoscopy should be performed for subjects at an older age (40 years and older), when increased serum pepsinogen II level is associated with decreased serum pepsinogen I and pepsinogen I to II ratio.
Topics: Alcohol Drinking; Biomarkers; Carcinoma; Diet; Disease Progression; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Metaplasia; Pepsinogen C; Smoking; Stomach; Stomach Neoplasms
PubMed: 24979566
DOI: No ID Found -
Cancer Epidemiology, Biomarkers &... Jul 2022Gastric 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...
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.
Topics: Biomarkers; Case-Control Studies; Early Detection of Cancer; Helicobacter Infections; Helicobacter pylori; Humans; Male; Pepsinogen A; Stomach Neoplasms; United States
PubMed: 35775231
DOI: 10.1158/1055-9965.EPI-22-0372 -
Helicobacter Apr 2022In the gastric mucosa, pepsinogen II (PgII) is produced/secreted by glands in the mucus-secreting antral and cardia compartments, but also by the chief cells and the... (Review)
Review
BACKGROUND AND AIM
In the gastric mucosa, pepsinogen II (PgII) is produced/secreted by glands in the mucus-secreting antral and cardia compartments, but also by the chief cells and the oxyntic glands. Increasing PgII serum levels are associated with the whole spectrum of gastric inflammatory diseases, including gastritis induced by Helicobacter pylori (H. pylori). This review critically addresses the clinical value of PgII serology for assessing gastric mucosal inflammation, and as a marker of H. pylori status, in both H. pylori-positive patients and after eradication therapy.
RESULTS
A search in PubMed/Scopus records yielded 39 out of 1190 published scientific studies meeting the selection criteria for this study. In the studies considered, PgII levels were significantly associated with non-atrophic gastric inflammatory lesions (p-values: 0.025-0.0001). H. pylori-positive patients had significantly higher PgII levels than H. pylori-negative individuals (p-values: 0.o5-0.0001). While a significant drop in serum PgII levels is consistently reported in H. pylori-eradicated patients (p-values: from 0.05 to 0.0001), inconsistencies in the related negative and positive predictive values significantly lower the clinical reliability of PgII testing by comparison with other available non-invasive tests.
CONCLUSIONS
PgII serology may provide clinically useful information on gastric inflammatory diseases, particularly if they are non-atrophic. PgII serology is inconsistent, however, for the purposes of distinguishing patients whose H. pylori eradication therapy is successful from those who remain infected.
Topics: Gastric Mucosa; Gastritis; Gastritis, Atrophic; Helicobacter Infections; Helicobacter pylori; Humans; Pepsinogen A; Pepsinogen C; Reproducibility of Results
PubMed: 34997989
DOI: 10.1111/hel.12872