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The role of autoimmunity in the pathogenesis of gastric cancer remains controversial. We studied antiparietal cell antibody (anti-PCA) and anti-intrinsic factor antibody (anti-IFA) levels and their associations with pepsinogen I/pepsinogen II levels in patients with gastric adenocarcinoma compared to a control group with mild or no atrophy of the stomach mucosa. Plasma levels of anti-PCA and anti-IFA were measured by ELISA (Inova Diagnostics Inc, San Diego, California, USA). The cutoff value for anti-PCA and anti-IFA positivity was ≥25â units. Altogether 214 patients (126 men, 88 women, median age 64.46, range: 35-86) with confirmed gastric adenocarcinoma and 214 control cases paired for age and sex were included in the study. Positive anti-PCA was present in 22 (10.3%) gastric cancer patients and controls (Pâ ≥â 0.999); positive anti-IFA in 6 (2.8%) and 4 (1.9.%), Pâ <â 0.232, respectively. We did not find significant differences in anti-PCA and anti-IFA positivity between gastric cancer patients and the control group; further investigation is required to better understand the potential involvement of autoimmune gastritis in the development of gastric cancer.
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Adenocarcinoma , Gastrite Atrófica , Gastrite , Infecções por Helicobacter , Helicobacter pylori , Neoplasias Gástricas , Masculino , Humanos , Feminino , Pessoa de Meia-Idade , Gastrite Atrófica/diagnóstico , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/patologia , Células Parietais Gástricas/patologia , Gastrinas , Gastrite/diagnóstico , Gastrite/patologia , Mucosa Gástrica/patologia , Biomarcadores , Adenocarcinoma/diagnóstico , Adenocarcinoma/patologia , Infecções por Helicobacter/patologiaRESUMO
OBJECTIVES: The aim of the study was to determine the proportion of gastric cancer patients with decreased levels of pepsinogen and gastrin-17 in plasma, with the goal of providing indirect evidence of the sensitivity of these biomarkers when applied in a cancer screening setting. METHODS: The levels of pepsinogens I and II, gastrin-17, and Helicobacter pylori immunoglobulin antibodies in plasma samples of gastric cancer patients were evaluated using the GastroPanel test system (Biohit Oyj, Helsinki, Finland). A decreased level of the pepsinogen I/II ratio was defined as less than three, while a decrease in gastrin-17 was defined as less than 1 pmol/L. Univariate analysis using non-parametric tests was used to investigate differences between normal and low concentrations of biomarkers. RESULTS: In total, 481 plasma samples from patients (59.9% male) with a median age of 64 years (ranging from 27 to 88 years) were analyzed. Out of the 400 cases of gastric cancer (83.2% of the total), 182 were categorized as the intestinal type, 141 as the diffuse type, 60 as the mixed type, and 17 as indeterminate according to the Lauren classification system. The H. pylori immunoglobulin test was positive in 74.0% of the patients. Pepsinogen I/II ratio was decreased in 32.4% (36.8% of the intestinal type); gastrin-17 in 12.3% (10.1% of the antral region) of all cases. CONCLUSION: The majority of gastric cancer patients had normal levels of pepsinogen and gastrin-17, suggesting that these biomarkers have limited application as screening tools in the Caucasian population.
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Infecções por Helicobacter , Helicobacter pylori , Neoplasias Gástricas , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Pepsinogênio A , Neoplasias Gástricas/diagnóstico , Infecções por Helicobacter/epidemiologia , Gastrinas , Biomarcadores , Anticorpos AntibacterianosRESUMO
Introduction−−Serum pepsinogen tests for gastric cancer screening have been debated for decades. We assessed the performance of two pepsinogen assays with or without gastrin-17 for the detection of different precancerous lesions alone or as a composite endpoint in a Latvian cohort. Methods−−Within the intervention arm of the GISTAR population-based study, participants with abnormal pepsinogen values by ELISA or latex-agglutination tests, or abnormal gastrin-17 by ELISA and a subset of subjects with all normal biomarker values were referred for upper endoscopy with biopsies. Performance of biomarkers, corrected by verification bias, to detect five composite outcomes based on atrophy, intestinal metaplasia, dysplasia or cancer was explored. Results−−Data from 1045 subjects were analysed, of those 273 with normal biomarker results. Both pepsinogen assays showed high specificity (>93%) but poor sensitivity (range: 18.4−31.1%) that slightly improved when lesions were restricted to corpus location (40.5%) but decreased when dysplasia and prevalent cancer cases were included (23.8%). Adding gastrin-17 detection, sensitivity reached 33−45% while specificity decreased (range: 61.1−62%) and referral rate for upper endoscopy increased to 38.6%. Conclusions−−Low sensitivity of pepsinogen assays is a limiting factor for their use in population-based primary gastric cancer screening, however their high specificity could be useful for triage.
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The accuracy of plasma pepsinogen (Pg) as a marker for precancerous gastric lesions (PGL) has shown variable results. We aimed to identify factors associated with false negative (FN) cases in Pg testing and to adjust cut-off values for these factors in order to improve Pg yield. Plasma Pg was measured and upper endoscopy with biopsy was performed within the "Multicentric randomized study of Helicobacter pylori eradication and pepsinogen testing for prevention of gastric cancer mortality: the GISTAR study". A multivariable logistic model was built for FN and multiple factors. Values of Pg were compared and sensitivity and specificity were calculated using pre-existing Pg cut-offs for factors showing strong associations with FN. New cut-offs were calculated for factors that showed substantially lower sensitivity. Of 1210 participants, 364 (30.1%) had histologically confirmed PGL, of which 160 (44.0%) were FN. Current smokers, men, and H. pylori positives were more likely FN. Smoking in H. pylori negatives was associated with a higher Pg I/II ratio and substantially lower sensitivity of Pg testing than in other groups. Adjusting Pg cut-offs for current smokers by H. pylori presence improved sensitivity for detecting PGL in this group. Our study suggests that adjusting Pg cut-offs for current smokers by H. pylori status could improve Pg test performance.
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OBJECTIVE: To identify dietary and lifestyle factors associated with decreased pepsinogen levels indicative of gastric atrophy. METHODS: Participants aged 40 to 64 from the "Multicentric randomized study of H. pylori eradication and pepsinogen testing for prevention of gastric cancer mortality (GISTAR study)" in Latvia tested for serum pepsinogen, as well as for Helicobacter pylori infection by 13 C-urea breath test or serology were included. Data on sex, age, education, employment, diet, smoking, alcohol and proton pump inhibitor use were obtained by survey and compared for participants with and without serologically detected gastric atrophy defined as pepsinogen I/pepsinogen II ≤ 2 and pepsinogen I ≤ 30 ng/mL. RESULTS: Of 3001 participants (median age 53, interquartile range, 11.0, 36.9% male) 52.8% had H. pylori and 7.7% had serologically detected gastric atrophy. In multivariate analysis, increasing age, consumption of alcohol, coffee, and onions were positively, while H. pylori , former smoking, pickled product and proton pump inhibitor use were inversely associated with gastric atrophy. Pepsinogen values were higher in smokers and those with H. pylori . Pepsinogen ratio was lower in those with H. pylori . When stratifying by H. pylori presence, significantly higher pepsinogen levels remained for smokers without H. pylori . CONCLUSION: Several dietary factors and smoking were associated with serologically detected gastric atrophy. Pepsinogen levels differed by smoking and H. pylori status, which may affect the serologic detection of gastric atrophy. There seems to be a complicated interaction between multiple factors. A prospective study including atrophy determined by both serology and histology is necessary.
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Gastrite Atrófica , Infecções por Helicobacter , Helicobacter pylori , Atrofia/complicações , Atrofia/patologia , Café , Feminino , Mucosa Gástrica/patologia , Gastrite Atrófica/diagnóstico , Gastrite Atrófica/patologia , Infecções por Helicobacter/complicações , Infecções por Helicobacter/diagnóstico , Infecções por Helicobacter/epidemiologia , Humanos , Estilo de Vida , Masculino , Pessoa de Meia-Idade , Pepsinogênio A , Pepsinogênio C , Estudos Prospectivos , Inibidores da Bomba de Prótons , UreiaRESUMO
BACKGROUND: Discrepancies between histology and serology results for Helicobacter pylori detection could be caused by a variety of factors, including a biopsy sampling error, expertise of the pathologist, natural loss of infection due to advanced atrophy, or a false-positive serology in the case of a previous infection, since antibodies may be present in blood following recovery from the infection. AIMS: To identify true H. pylori-positive individuals in discrepant cases by serology and histology using real time polymerase chain reaction (RT-PCR) as a gold standard. METHODS: Study subjects with discrepant histology and serology results were selected from the GISTAR pilot study data base in Latvia. Subjects having received previous H. pylori eradication therapy or reporting use of proton pump inhibitors, antibacterial medications, or bismuth containing drugs one month prior to upper endoscopy were excluded. We compared the discrepant cases to the corresponding results of RT-PCR performed on gastric biopsies. RESULTS: In total, 97 individuals with discrepant results were identified: 81 subjects were serology-positive/histology-negative, while 16 were serology-negative/histology-positive. Among the serology-positive/histology-negative cases, 64/81 (79.0%) were false-positives by serology and, for the majority, inflammation was absent in all biopsies, while, in the serology-negative/histology-positive group, only 6.2% were proven false-positives by histology. CONCLUSIONS: Among this high H. pylori prevalent, middle-aged population, the majority of discrepant cases between serology and histology were due to false positive-serology, rather than false-negative histology. This confirms the available evidence that the choice of treatment should not be based solely on the serological results, but also after excluding previous, self-reported eradication therapy.
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BACKGROUND & AIMS: A genome-wide significant association between anti-Helicobacter pylori (H pylori) IgG titers and Toll-like receptor (TLR1/6/10) locus on 4p14 was demonstrated for individuals of European ancestry, but not uniformly replicated. We re-investigated this association in an updated genome-wide association study (GWAS) meta-analysis for populations with low gastric cancer incidence, address potential causes of cohort heterogeneity, and explore functional implications of genetic variation at the TLR1/6/10 locus. METHODS: The dichotomous GWAS (25% individuals exhibiting highest anti-H pylori IgG titers vs remaining 75%) included discovery and replication sampls of, respectively, n = 15,685 and n = 9676, all of European ancestry. Longitudinal analysis of serologic data was performed on H pylori-eradicated subjects (n = 132) and patients under surveillance for premalignant gastric lesions (n = 107). TLR1/6/10 surface expression, TLR1 mRNA, and cytokine levels were measured in leukocyte subsets of healthy subjects (n = 26) genotyped for TLR1/6/10 variants. RESULTS: The association of the TLR1/6/10 locus with anti-H pylori IgG titers (rs12233670; ß = -0.267 ± SE 0.034; P = 4.42 × 10-15) presented with high heterogeneity and failed replication. Anti-H pylori IgG titers declined within 2-4 years after eradication treatment (P = 0.004), and decreased over time in patients with premalignant gastric lesions (P < 0.001). Variation at the TLR1/6/10 locus affected TLR1-mediated cytokine production and TLR1 surface expression on monocytes (P = 0.016) and neutrophils (P = 0.030), but not mRNA levels. CONCLUSIONS: The association between anti-H pylori IgG titers and TLR1/6/10 locus was not replicated across cohorts, possibly owing to dependency of anti-H pylori IgG titers on therapy, clearance, and antibody decay. H pylori-mediated immune cell activation is partly mediated via TLR1 signaling, which in turn is affected by genetic variation.
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Infecções por Helicobacter , Helicobacter pylori , Neoplasias Gástricas , Receptor 1 Toll-Like/genética , Anticorpos Antibacterianos , Citocinas/genética , Estudo de Associação Genômica Ampla , Infecções por Helicobacter/diagnóstico , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/genética , Humanos , Imunoglobulina G , Neoplasias Gástricas/genéticaRESUMO
BACKGROUND: Helicobacter pylori (H. pylori) infection is associated with several risk factors such as demographic, socioeconomic status and personal habits, which vary in different populations. This is the most up-to-date data on H. pylori prevalence and potential risk factors for H. pylori infection among asymptomatic middle-aged individuals in Kazakhstan. METHODS: Apparently healthy individuals aged 40 to 64, who took part in the health control in the outpatient clinic, were invited to participate in the study; answered a questionnaire, donated a blood sample. The antibodies to H. pylori were analysed by latex agglutination method. The baseline characteristics of study subjects with or without H. pylori infection were compared using the Chi-square test. Odds ratio (OR) and 95% confidence intervals (CI) for the association between H. pylori infection and potential risk factors were estimated using multivariable logistic regression models. RESULTS: Altogether 166 subjects (59% male; the median age - 51 years old) were included; 104 (62.7%) were H. pylori positive. There were no statistically significant differences between H. pylori positive and H. pylori negative groups in respect to the gender, anthropometric measurements, socioeconomic factors and personal habits. The multiple variable analysis showed that age (OR, 1.99; 95% CI, 1.03 - 3.86; P=0.04) and increased salt intake (OR, 2.21; 95% CI, 1.12 - 4.35; P=0.02) were associated with H. pylori infection. CONCLUSIONS: More than half of the study subjects were infected with H. pylori in Kazakhstan. The prevalence of H. pylori infection was independently associated with older age and regular high salt consumption.
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Infecções Assintomáticas/epidemiologia , Infecções por Helicobacter/epidemiologia , Helicobacter pylori , Adulto , Fatores Etários , Dieta , Feminino , Infecções por Helicobacter/diagnóstico , Humanos , Cazaquistão , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Prevalência , Fatores de Risco , Fatores SocioeconômicosRESUMO
BACKGROUND: Atrophic gastritis is considered precursor condition for gastric cancer. There is so far limited evidence on the performance of pepsinogens for atrophy detection in Central Asia. The aim of our study was to detect the prevalence of atrophic gastritis in the asymptomatic adult population in Kazakhstan as well as address the accuracy of pepsinogen testing in atrophy detection. METHODS: Healthy individuals aged 40-64 were included. Upper endoscopy and pepsinogens (PG) evaluation were performed. PG were analysed in plasma by latex agglutination. Cut off values were used to define decreased PG values (PGR ≤ 3 and PG I ≤ 70 ng/mL); severely decreased PG values (PGR ≤ 2 and PG I ≤ 30 ng/mL). Biopsies were analyzed and obtained according to the updated Sydney System. PG test sensitivity, specificity and overall accuracy were assessed using the histological diagnosis as the "gold standard". RESULTS: Altogether 157 individuals - female 40,1% and male 59,9% were included. Histologically, moderate to severe corpus atrophy, was present only in 1,3% cases. From all study subjects, 26,8% had decreased plasma PG values with cut-off values PGR ≤ 3 and PG I ≤ 70 ng/mL. The sensitivity of the PG test with this cut-off values was 50,0%, specificity 73,5%, overall accuracy 73,2% for detection of moderate to severe atrophy in the corpus. The sensitivity of PG test with cut-off values PGR ≤ 2 and PG I ≤30 ng/mL was 50,0%, specificity 90,9% and overall accuracy 90,4%. CONCLUSIONS: The prevalence of gastric mucosal atrophy was low in the Kazakh population. Serological PG test screening nevertheless can play an important role in the diagnosis of gastric precancerous lesions. However, the diagnostic accuracy of the PG test is mainly dependent on the cut-off values for positive results.
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Mucosa Gástrica/patologia , Gastrite Atrófica/epidemiologia , Pepsinogênio A/sangue , Adulto , Atrofia/sangue , Atrofia/diagnóstico , Atrofia/epidemiologia , Endoscopia , Feminino , Seguimentos , Mucosa Gástrica/metabolismo , Gastrite Atrófica/sangue , Gastrite Atrófica/diagnóstico , Gastrite Atrófica/patologia , Humanos , Cazaquistão/epidemiologia , Masculino , Pessoa de Meia-Idade , Prevalência , Prognóstico , Curva ROCRESUMO
Epstein-Barr virus (EBV)-positive gastric adenocarcinoma exhibits locally intense inflammation but systemic manifestations are uncertain. Our study examined whether circulating mediators of inflammation and immune response differ by tumor EBV status. From a Latvian series of 302 gastric cancer cases, we measured plasma levels of 92 immune-related proteins in the 28 patients with EBV-positive tumors and 34 patients with EBV-negative tumors. Eight markers were statistically significantly higher with tumor EBV positivity: chemokine C-C motif ligand (CCL) 20 (Odds Ratio (OR) = 3.6; p-trend = 0.001), chemokine C-X-C motif ligand 9 (OR = 3.6; p-trend = 0.003), programmed death-ligand 1 (PD-L1; OR = 3.4; p-trend = 0.004), interleukin (IL)-10 (OR = 2.4; p-trend = 0.019), CCL19 (OR = 2.3; p-trend = 0.019), CCL11 (OR = 2.2; p-trend = 0.026), IL-17A (OR = 2.0; p-trend = 0.038) and CCL8 (OR = 1.9; p-trend = 0.049). Systemic responses to EBV-positive gastric cancer are characterized by alterations in chemokines and PD-L1. Profiling of these molecules may enable non-invasive diagnosis of EBV status when tumor tissue is unavailable. Our findings provide theoretical justification for clinical evaluations of immune checkpoint therapy for EBV-positive gastric cancer.
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OBJECTIVE: The aim of the study was to assess the accuracy of two plasma Helicobacter pylori (H. pylori) antibody test-systems and a stool antigen test (SAT) system in a general population sample in Latvia. MATERIALS AND METHODS: Blood and faecal samples were analysed in healthy individuals (40-64 years), referred for upper gastrointestinal endoscopy according to pilot study protocol within a population-based study investigating gastric cancer prevention strategies (GISTAR pilot study). Antibodies to H. pylori were assessed in plasma by latex-agglutination test and enzyme-linked immunosorbent assay (ELISA). H. pylori antigen in faecal samples was detected by a monoclonal enzyme immunoassay-based SAT. Histological assessment of H. pylori based on a modified Giemsa staining method was used as the gold standard. Individuals having received H. pylori eradication within one year prior to enrolment were excluded. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and overall accuracy were calculated. Receiver-operating characteristic curves were designed to estimate the optimal diagnostic cut-off value of tests. RESULTS: The analysis included 779 participants for latex-agglutination test, 1002 for ELISA and 672 individual samples for SAT. The sensitivity, specificity, PPV, NPV and overall accuracy were as follows: latex-agglutination test (86;81;87;80;84%), ELISA (97;72;83;94;86%) and SAT (87;81;87;81;85%), respectively. The optimal diagnostic cut-off value for ELISA test was ≥50.26 g/L. CONCLUSIONS: Although the performance of the three tests was comparable to each other, the three test systems showed suboptimal accuracy, with important implications for public health programs based on 'test-and-treat' strategy.
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Anticorpos Antibacterianos/sangue , Antígenos de Bactérias/análise , Fezes/química , Infecções por Helicobacter/diagnóstico , Testes Sorológicos/normas , Adulto , Ensaio de Imunoadsorção Enzimática , Feminino , França , Helicobacter pylori , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Curva ROC , Sensibilidade e EspecificidadeRESUMO
AIMS: The aim of the study was to evaluate the rationale of blood pepsinogen (PG) testing in population based screening settings. METHODS: Participants from a cross-sectional population-based study of cardiovascular risk factors in Latvia were invited to participate in the current study. Pepsinogen I and II were measured in blood samples taken during the initial study and at follow-up; upper gastrointestinal endoscopy was performed. There were three groups of patients: with moderately decreased (PG I< 70 ng/ml and PG I/PG II ratio < 3), with strongly decreased (PG I< 30 ng/ml and PG I/PG II ratio < 2), and with normal PG level. Biopsy with H. pylori detection was performed (updated Sydney system). RESULTS: Results from 259 patients were analyzed. Pepsinogens were decreased in 133 (51.4%), H. pylori was positive in 177 (66.0%) cases. Mean age was significantly lower in patients with normal compared to strongly decreased PG level group (52.8 vs. 64.1 years, p<0.001). Prevalence of severe corpus atrophy was higher in the strongly decreased compared to the normal PG test group: 7.0% vs. 0%; the same tendency was noted in the distribution of OLGA stages III-IV - 10.5% and 0.0%, OLGIM stages III-IV - 3.5% and 0%, and low-grade dysplasia - 15.8% and 2.4% (p<0.05). Two cases of gastric cancer were found; both presented decreased PG levels. A strong association between H. pylori eradication and PG ratio dynamics was found (p<0.05). CONCLUSIONS: All high-risk lesions were found in the decreased PG test groups; two cancer cases were revealed. However, PG demonstrated low specificity and low value of repeated testing. The value of PG as a sole test for gastric cancer risk is limited.
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Gastrite/diagnóstico , Pepsinogênio A/sangue , Pepsinogênio C/sangue , Neoplasias Gástricas/diagnóstico , Estômago/patologia , Adulto , Idoso , Atrofia/sangue , Fenômenos Fisiológicos da Nutrição do Idoso , Endoscopia Gastrointestinal , Feminino , Gastrite/sangue , Gastrite/patologia , Infecções por Helicobacter/sangue , Helicobacter pylori , Humanos , Masculino , Programas de Rastreamento , Pessoa de Meia-Idade , Neoplasias Gástricas/sangue , Neoplasias Gástricas/patologiaRESUMO
INTRODUCTION: Population-based eradication of Helicobacter pylori has been suggested to be cost-effective and is recommended by international guidelines. However, the potential adverse effects of widespread antibiotic use that this would entail have not been sufficiently studied. An alternative way to decrease gastric cancer mortality is by non-invasive search for precancerous lesions, in particular gastric atrophy; pepsinogen tests are the best currently available alternative. The primary objective of GISTAR is to determine whether H pylori eradication combined with pepsinogen testing reduces mortality from gastric cancer among 40-64-year-old individuals. The secondary objectives include evaluation of H pylori eradication effectiveness in gastric cancer prevention in patients with precancerous lesions and evaluation of the potential adverse events, including effects on microbiome. METHODS AND ANALYSIS: Individuals are recruited from general population (50% men) in areas with high gastric cancer risk in Europe and undergo detailed lifestyle and medical history questionnaire before being randomly allocated to intervention or control groups. The intervention group undergoes H pylori testing and is offered eradication therapy if positive; in addition, pepsinogen levels are detected in plasma and those with decreased levels are referred for upper endoscopy. All participants are offered faecal occult blood testing as an incentive for study participation. Effectiveness of eradication and the spectrum of adverse events are evaluated in study subpopulations. A 35% difference in gastric cancer mortality between the groups is expected to be detectable at 90% power after 15 years if 30 000 individuals are recruited. Biological materials are biobanked for the main and ancillary studies. The study procedure and assumptions will be tested during the pilot phase. ETHICS AND DISSEMINATION: The study was approved by the respective ethics committees. An independent Data Safety and Monitoring Board has been established. The findings will be published in peer-reviewed journals and presented at scientific meetings. TRIAL REGISTRATION NUMBER: NCT02047994.
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Antibacterianos/uso terapêutico , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori/efeitos dos fármacos , Pepsinogênio A/sangue , Lesões Pré-Cancerosas/diagnóstico , Neoplasias Gástricas/prevenção & controle , Estômago/patologia , Adulto , Antibacterianos/farmacologia , Europa (Continente) , Feminino , Gastroscopia , Infecções por Helicobacter/complicações , Infecções por Helicobacter/microbiologia , Infecções por Helicobacter/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Mortalidade , Lesões Pré-Cancerosas/patologia , Projetos de Pesquisa , Estômago/efeitos dos fármacos , Estômago/microbiologia , Neoplasias Gástricas/etiologia , Neoplasias Gástricas/microbiologia , Neoplasias Gástricas/patologiaRESUMO
BACKGROUND: Circulating levels of pepsinogens have been used in high gastric cancer-risk Asian and European populations to triage endoscopic evaluation for more severe pathology. There are different analytic methods with uncertain correlations. We therefore compared diagnostic performance of three commonly used pepsinogen assays to detect histologically confirmed gastric atrophy. METHODS: We tested plasma samples from adult patients with (n=50) and without (n=755) moderate or severe gastric corpus atrophy, as determined histologically by consensus of three expert pathologists. A single laboratory measured pepsinogens I (PgI) and II (PgII) using commercially available assays: two ELISA assays produced by Biohit (Finland) and Vector Best (Russia), and a latex agglutination assay from Eiken (Japan). Quantitative correlations were assessed by Spearman statistics. Receiver operating characteristic (ROC) curves vs histological diagnosis were calculated using both the manufacturers' and optimized cutoffs. RESULTS: Pepsinogen levels were highly correlated among the assays (pairwise Rhos: PgI≥0.84, PgII≥0.87; all P-values<.01). Based on manufacturers' cutoffs, sensitivities, specificities and areas under the ROC curve for detecting moderate to severe histological corpus atrophy by PgI/PgII were 44%/91%/0.70, 56%/84%/0.76, and 52%/90%/0.77 for Biohit, Vector Best and Eiken, respectively. Cutoffs optimized by ROC or data mining analyses did not substantially improve test performance. CONCLUSIONS: Commercial assays for pepsinogen have good relative agreement but are imperfect tests for clinical diagnosis of gastric atrophy. IMPACT: Pepsinogen testing alone does not provide sufficient information for gastric cancer risk stratification. Future investigations should focus on other potential markers, in combination with pepsinogens.
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Atrofia/diagnóstico , Testes Diagnósticos de Rotina/métodos , Ensaio de Imunoadsorção Enzimática/métodos , Mucosa Gástrica/patologia , Testes de Fixação do Látex/métodos , Pepsinogênios/sangue , Gastropatias/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Atrofia/patologia , Feminino , Histocitoquímica , Humanos , Masculino , Pessoa de Meia-Idade , Curva ROC , Gastropatias/patologia , Adulto JovemRESUMO
BACKGROUND: Secretion of pepsinogen I (PgI), pepsinogen II (PgII), fasting gastrin-17 (fG-17) and stimulated gastrin-17 (sG-17) changes after Helicobacter pylori eradication. Few data are available on the long-term dynamics of gastric biomarkers after H. pylori eradication.The aim of this study was to investigate the dynamics of gastric biomarkers in H. pylori-positive patients after eradication over a 3-year period and to compare the levels with initially H. pylori-negative patients. MATERIALS AND METHODS: Blood samples for the detection of gastric biomarkers were obtained from dyspeptic patients coming for upper gastrointestinal endoscopy. In H. pylori-positive patients, after eradication therapy, three follow-up blood samples were drawn after 12, 24 and 36 months; in H. pylori-negative patients, two samples were taken - at 12 and after 30 months. Median values of biomarkers in follow-up samples were compared with the baseline sample. RESULTS: The final sample included 110 patients (median age 67 years, M/F ratio 27/83). In patients after H. pylori eradication (n=83) PgI, PgII, fG-17 and sG-17 had decreased significantly during a 36-month period, whereas the PgI/PgII ratio had increased significantly from 5.59 to 11.64. CONCLUSION: In H. pylori-positive dyspeptic patients, after eradication therapy, a decrease in PgI, PgII, fG-17 and sG-17 was observed after 36 months whereas an increase in the PgI/II ratio suggested an improvement in gastric atrophy. The median levels of gastric biomarkers in patients after H. pylori eradication therapy may become similar to biomarker levels among initially H. pylori-negative individuals.
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Gastrinas/sangue , Infecções por Helicobacter/sangue , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori , Pepsinogênio A/sangue , Pepsinogênio C/sangue , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Dispepsia/sangue , Dispepsia/microbiologia , Endoscopia Gastrointestinal , Jejum , Feminino , Seguimentos , Infecções por Helicobacter/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de TempoRESUMO
OBJECTIVES: Helicobacter pylori infection and atrophic gastritis are related to an increased risk for gastric cancer. There is a decrease in global H. pylori prevalence. We analyzed the prevalence of H. pylori infection in Latvia by the plasma IgG test and the presence of atrophy by means of pepsinogen testing. METHODS: This subanalysis was carried out on a randomly selected cross-sectional sample of a general population of adults to access cardiovascular risk factors. Plasma samples were screened for H. pylori IgG (cutoff value 24 U/ml), and pepsinogens (Pg) I and II. Pg cutoff values of PgI/PgII ≤ 3 and PgI ≤ 70 ng/ml were used to assess the prevalence of atrophy of any grade and PgI/PgII ≤ 2 and PgI ≤ 30 ng/ml for advanced atrophy. RESULTS: Altogether, 3564 serum samples were available for the study (2346 women, 1218 men; median age 54 years). Of the tested individuals, 79.21% were H. pylori positive, with no difference between sexes. The prevalence increased with age (P<0.001). Atrophy of any grade was identified in 1444 individuals (40.52%) and advanced atrophy in 475 individuals (13.33%). Linear association with age was present in both response types (P<0.001). The prevalence of atrophy of any grade was higher in women (41.73%) than in men (38.18%; P=0.04); this difference was lost for advanced atrophy (women 13.98%, men 12.07%; P=0.1). CONCLUSION: The prevalence of H. pylori infection or atrophy remains high in Latvia. Determining the right cutoff value is critically important for pepsinogen-based atrophy detection in Europe in order to objectively stratify gastric cancer risk.
Assuntos
Gastrite Atrófica/epidemiologia , Infecções por Helicobacter/epidemiologia , Helicobacter pylori/isolamento & purificação , Lesões Pré-Cancerosas/epidemiologia , Neoplasias Gástricas/epidemiologia , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Anticorpos Antibacterianos/sangue , Biomarcadores/sangue , Distribuição de Qui-Quadrado , Estudos Transversais , Feminino , Gastrite Atrófica/diagnóstico , Gastrite Atrófica/microbiologia , Infecções por Helicobacter/diagnóstico , Infecções por Helicobacter/microbiologia , Helicobacter pylori/imunologia , Humanos , Letônia/epidemiologia , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Pepsinogênio A/sangue , Pepsinogênio C/sangue , Lesões Pré-Cancerosas/diagnóstico , Lesões Pré-Cancerosas/microbiologia , Valor Preditivo dos Testes , Prevalência , Fatores de Risco , Índice de Gravidade de Doença , Fatores Sexuais , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/microbiologia , Adulto JovemRESUMO
BACKGROUND: Decreased density of H. pylori in atrophic gastritis may lead to low sensitivity of the routine tests. AIMS: To evaluate the accuracy of routinely used H. pylori tests in atrophic gastritis. METHODS: We compared 5 H. pylori diagnostic tests in 119 dyspeptic patients (28 males/91 females) with a mean age of 67 years (range 55-84). Patients with gastric cancer, peptic ulcer, previous gastric surgery, or those who have received eradication therapy were excluded. The following tests were performed: histology, rapid urease test (RUT), culture, 13C- urea breath tests (UBT), and H.pylori IgG/IgA antibody test (serology). RESULTS: Atrophic gastritis was diagnosed in 26.1% of the patients; H. pylori was present in 87.1%. In the group with atrophy, the sensitivity, specificity, positive predictive value, negative predictive value and overall accuracy were as follows: histology (100% for all parameters); UBT (96; 100; 100; 80; 97%); serology (96; 50; 93; 67; 90%); culture (96; 100; 100; 80; 97%); and RUT (78; 100; 100; 40; 81%), respectively. CONCLUSIONS: Histology, UBT and culture were the three best tests for diagnosing H. pylori infection. We cannot recommend using serology as a single test in a case of atrophy, but it would be reasonable to combine serology with one of the above tests.