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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 -
Digestive and Liver Disease : Official... Dec 2019Chronic atrophic gastritis (CAG) is an underdiagnosed condition characterised by translational features going beyond the strict field of gastroenterology as it may...
Chronic atrophic gastritis: Natural history, diagnosis and therapeutic management. A position paper by the Italian Society of Hospital Gastroenterologists and Digestive Endoscopists [AIGO], the Italian Society of Digestive Endoscopy [SIED], the Italian Society of Gastroenterology [SIGE], and the...
Chronic atrophic gastritis (CAG) is an underdiagnosed condition characterised by translational features going beyond the strict field of gastroenterology as it may manifest itself by a variable spectrum of gastric and extra-gastric symptoms and signs. It is relatively common among older adults in different parts of the world, but large variations exist. Helicobacter pylori-related CAG [multifocal] and autoimmune CAG (corpus-restricted) are apparently two different diseases, but they display overlapping features. Patients with cobalamin and/or iron deficiency anaemia or autoimmune disorders, including autoimmune thyroiditis and type 1 diabetes mellitus, should be offered screening for CAG. Pepsinogens, gastrin-17, and anti-H. pylori antibodies serum assays seem to be reliable non-invasive screening tools for the presence of CAG, helpful to identify individuals to refer to gastroscopy with five standard gastric biopsies in order to obtain histological confirmation of diagnosis. Patients with CAG are at increased risk of developing gastric cancer, and they should be estimated with histological staging systems (OLGA or OLGIM). H. pylori eradication may be beneficial by modifying the natural history of atrophy, but not that of intestinal metaplasia. Patients with advanced stages of CAG (Stage III/IV OLGA or OLGIM) should undergo endoscopic surveillance every three years, those with autoimmune CAG every three-five years. In patients with CAG, a screening for autoimmune thyroid disease and micronutrient deficiencies, including iron and vitamin B, should be performed. The optimal treatment for dyspeptic symptoms in patients with CAG remains to be defined. Proton pump inhibitors are not indicated in hypochlorhydric CAG patients.
Topics: Autoimmune Diseases; Biopsy; Deficiency Diseases; Endoscopy, Gastrointestinal; Gastritis, Atrophic; Helicobacter Infections; Humans; Italy; Patient Care Management; Risk Factors
PubMed: 31635944
DOI: 10.1016/j.dld.2019.09.016 -
Gut May 2021An unmet need exists for a non-invasive biomarker assay to aid gastric cancer diagnosis. We aimed to develop a serum microRNA (miRNA) panel for identifying patients with...
OBJECTIVE
An unmet need exists for a non-invasive biomarker assay to aid gastric cancer diagnosis. We aimed to develop a serum microRNA (miRNA) panel for identifying patients with all stages of gastric cancer from a high-risk population.
DESIGN
We conducted a three-phase, multicentre study comprising 5248 subjects from Singapore and Korea. Biomarker discovery and verification phases were done through comprehensive serum miRNA profiling and multivariant analysis of 578 miRNA candidates in retrospective cohorts of 682 subjects. A clinical assay was developed and validated in a prospective cohort of 4566 symptomatic subjects who underwent endoscopy. Assay performance was confirmed with histological diagnosis and compared with (HP) serology, serum pepsinogens (PGs), 'ABC' method, carcinoembryonic antigen (CEA) and cancer antigen 19-9 (CA19-9). Cost-effectiveness was analysed using a Markov decision model.
RESULTS
We developed a clinical assay for detection of gastric cancer based on a 12-miRNA biomarker panel. The 12-miRNA panel had area under the curve (AUC)=0.93 (95% CI 0.90 to 0.95) and AUC=0.92 (95% CI 0.88 to 0.96) in the discovery and verification cohorts, respectively. In the prospective study, overall sensitivity was 87.0% (95% CI 79.4% to 92.5%) at specificity of 68.4% (95% CI 67.0% to 69.8%). AUC was 0.848 (95% CI 0.81 to 0.88), higher than HP serology (0.635), PG 1/2 ratio (0.641), PG index (0.576), ABC method (0.647), CEA (0.576) and CA19-9 (0.595). The number needed to screen is 489 annually. It is cost-effective for mass screening relative to current practice (incremental cost-effectiveness ratio=US$44 531/quality-of-life year).
CONCLUSION
We developed and validated a serum 12-miRNA biomarker assay, which may be a cost-effective risk assessment for gastric cancer.
TRIAL REGISTRATION NUMBER
This study is registered with ClinicalTrials.gov (Registration number: NCT04329299).
Topics: Aged; Biomarkers, Tumor; Case-Control Studies; Early Detection of Cancer; Female; Gastroscopy; Humans; Male; Markov Chains; Mass Screening; MicroRNAs; Middle Aged; Neoplasm Staging; Prospective Studies; Republic of Korea; Retrospective Studies; Sensitivity and Specificity; Singapore; Stomach Neoplasms
PubMed: 33028667
DOI: 10.1136/gutjnl-2020-322065 -
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 -
Saudi Journal of Gastroenterology :... 2023Screening for chronic atrophic gastritis (CAG) is crucial for the prevention and early detection of gastric cancer. Endoscopy is the main method of CAG diagnosis, with...
BACKGROUND
Screening for chronic atrophic gastritis (CAG) is crucial for the prevention and early detection of gastric cancer. Endoscopy is the main method of CAG diagnosis, with high training requirements and limited accuracy, making it difficult to popularize. The study attempts to improve the positive rate and accuracy of CAG screening through non-invasive testing.
METHODS
A total of 2564 patients who underwent gastroscopy were included in this study. The results of gastroscopic evaluation, histological biopsy results (including H. pylori biopsy), urea breath test (UBT) results, serum pepsinogen, and testosterone were statistically analyzed.
RESULTS
We found significant differences in the diagnosis of CAG between endoscopy and histological biopsy. Pepsinogen II and pepsinogen I/II ratio were more useful for the diagnosis of CAG compared with pepsinogen I. The risk of CAG was increased when pepsinogen II exceeded 11.05 μg/L, and the pepsinogen I/II ratio was less than 3.75. CAG positivity was higher in patients with positive H. pylori infection on UBT screening. In addition, higher levels of testosterone, SHBG and HSD17B2, and lower level of GNRH1 were found in CAG mucosa. Patients with high serum testosterone had a higher risk of CAG.
CONCLUSION
CAG screening should be combined with endoscopic evaluation, biopsy, and other non-invasive tests. Non-invasive tests include the combination of serum pepsinogen II protein and pepsinogen I/II ratio and high level of serum testosterone. UBT combined with serum pepsinogen testing may improve the positive rate of CAG and reduce gastric mucosal damage from multiple biopsies.
Topics: Humans; Gastritis, Atrophic; Pepsinogen A; Pepsinogen C; Risk Factors; Testosterone; Helicobacter pylori; Helicobacter Infections
PubMed: 36588366
DOI: 10.4103/sjg.sjg_383_22 -
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