Helicobacter pylori-Positive Gastric Biopsies-Association with Clinical Predictors.

Introduction: Although Helicobacter pylori's role in gastric oncogenesis is well-known, only a fraction of infected patients develop cancer. Hence, more factors are supposed to be involved. The objectives of the present study were to investigate the impact of clinicopathological parameters on Helicobacter pylori status. Methods: The study included 1522 patients referred for endoscopy: study group consisted of 557 patients with Helicobacter pylori-positive biopsies confirmed using histochemical stains or immunohistochemistry methods; and the control group consisted of 965 patients with Helicobacter pylori-negative status on histology. Results: Severe endoscopic lesions were more frequent in the Helicobacter pylori group (p < 0.001), with no difference noticed in the distribution of premalignant gastric lesions (p = 0.82). Anemia and dyslipidemia were independent factors associated with Helicobacter pylori-positive biopsies (p < 0.05). Non-steroidal anti-inflammatory therapy was more frequently administered in the study group, while proton-pump inhibitors had an anti-Helicobacter pylori activity on histology (p < 0.0001). Conclusion: In the studied population, patients with Helicobacter pylori-positive biopsies had a more frequent history of gastrotoxic medication, severe endoscopic lesions, and anemia. Helicobacter pylori was unpredictable by gastrointestinal symptoms. The frequency of premalignant gastric lesions was similar irrespective of the actual status of infection, underlining the importance of unintentional clearance of bacteria in old infection and the remaining risk for cancer in this population.

Factors associated with gastro-duodenal ulcer in compensated type 2 diabetic patients: a Romanian single-center study.

INTRODUCTION: Helicobacter pylori infection is accepted as the leading cause of chronic gastritis, ulcer disease and gastric cancer, with an important impact on health care burden, especially in countries with a high prevalence of infection. The aim of the study was to investigate the influence of H. pylori infection, medication, associated medical conditions or social habits on endoscopic ulcer occurrence in the compensated type 2 diabetic population. MATERIAL AND METHODS: Two hundred and sixty type 2 diabetic patients investigated on endoscopy (57 patients with peptic ulcer and 203 controls) with a complete set of biopsies, demographic and medical data were enrolled. RESULTS: On univariate regression analysis, H. pylori infection (42.1% vs. 35.5%, p = 0.359) or a history of peptic ulcer (61.4% vs. 61.6%, p = 0.981) was not a predictor for ulcer on endoscopy in the diabetic population, and heartburn was more frequent in diabetics without ulcer (21.2% vs. 8.8%, p = 0.033). Anemia was the best predictor for ulcer on endoscopy in both diabetics with (p < 0.001, OR = 4.77, 95% CI: 2.02-11.28) and without (p = 0.027, OR = 2.76, 95% CI: 1.10-6.91) chronic proton pump inhibitor (PPI) therapy. In diabetic patients on PPI more than 1 month anticoagulants - acenocoumarol or low-weight molecular heparin (p = 0.038, OR = 2.37, 95% CI: 1.04-5.40), low-dose aspirin 75-125 mg/day (p = 0.029, OR = 2.61, 95% CI: 1.08-6.28) and alcohol consumption (p = 0.015, OR = 2.70, 95% CI: 1.19-6.13) were predictors for ulcer on endoscopy. CONCLUSIONS: In diabetic patients, anemia is the most important predictor for ulcer on endoscopy, but not H. pylori or digestive symptoms, while low-dose aspirin or anticoagulant therapy and alcohol consumption are the most important predictors for ulcer in diabetics on chronic proton pump inhibitor therapy.

Demographic, hematologic, and endoscopic differences between predominant corporeal and antral atrophic gastritis: A STROBE-Compliant study.

ABSTRACT: The study aimed to assess demographic, clinical, and endoscopic parameters in patients with predominant corporeal atrophic gastritis (CAG) and enterochromaffin-like cell hyperplasia suggestive for autoimmune etiology in comparison with patients presenting Helicobacter pylori atrophic gastritis limited to the gastric antrum (AAG).Demographical, clinical, and pathological data of consecutive patients who underwent an upper digestive endoscopy for bleeding screening risk, symptoms, or anemia in a single endoscopy unit were retrieved. The final study group included 63 patients with CAG and enterochromaffin-like cell hyperplasia on histology and a control group of 142 patients with AAG.Female patients were predominant in the group with CAG versus AAG (69.8% vs 46.4%, P = .002). Microcytic anemia (P < .001), but not macrocytic anemia (P = .14) was associated with CAG, the mean corpuscular volume of erythrocyte (MCV) (82.5 vs 86.5 fl, P = .01), the mean value of serum iron (11.8 vs 14.3 µmol/L, P = .02), and hemoglobin level (11.0 vs 12.7 g/dL P < .01) being significantly lower in patients with CAG versus AAG. Upper digestive endoscopies with no visible mucosal lesions (P = .01) were also more frequent in the patients with CAG, but there were not differences regarding digestive symptoms between groups. The linear regression models revealed that the low hemoglobin (P < .001) and low MCV (P = .03) are the independent variables that can predict CAG on histology, but not the serum iron level (P = .77)Consecutive patients investigated on endoscopy with CAG in comparison with those having AAG are more frequent female, they have microcytic anemia, and no mucosal lesions on endoscopy. The decreased hemoglobin level and low MCV, rather than the serum iron level are predictors for CAG versus AAG on histology in endoscopic population.

Cytokine TGF-ß1, TNF-α, IFN-γ and IL-6 Gene Polymorphisms and Localization of Premalignant Gastric Lesions in Immunohistochemically H. pylori-negative Patients.

Background: Cytokines and their gene variants are proven to play a role in pathogenic gastritis and carcinogenesis. The study assesses associations of the cytokine gene polymorphisms with extension of atrophic gastritis/intestinal metaplasia (AGIM) in patients without Helicobacter pylori infection on immunohistochemistry study. Methods: 224 adult consecutive patients undergoing an upper digestive endoscopy were included and grouped according to localization of AGIM: 37 patients with antrum-limited AGIM, 21 corpus-limited AGIM, 15 extended-AGIM (antrum and corpus) and 151 patients had no AGIM. Medical records of the patients were checked and a structured direct interview was applied in order to collect clinical data, including digestive symptoms. In all cases, IFN-γ +874T>A, TGF-ß1 +869T>C, TNF-α-308G>A and -238G>A, and IL-6 -174C>G polymorphisms were genotyped. Results: The mean age was significantly higher in the AGIM group, while the comorbidies were similar among patients with different localization of lesions or in patients without AGIM. There were no significant differences in digestive symptoms, nor in the consumption of non-steroidal anti-inflammatory drugs or proton pump inhibitor with the different extensions of AGIM. There was a significant association between oral anticoagulant consumption and localization of AGIM (P = 0.042), frequency being higher among patients with corpus-limited AGIM than those with no AGIM (P = 0.007, adjusted P = 0.041). TGF-ß1 +869T>C was less frequent among patients with corpus-limited AGIM (n=7, 33.3%) and extended AGIM (n=5, 33.3%) than in antrum-limited AGIM (n=25, 67.6%). There were no other significant differences regarding variant and wild genotype frequencies of IFN-γ +874T>A (86.5%, 81.0%, 86.7%, p=0.814), TNF-α-308G>A (35.1%, 28.6%, 53.3%, p=0.48) and IL-6 -174C>G (70.3%. 61.9%, 73.3% p=0.656) among patients with antrum-limited, corpus-limited or extended AGIM. TGF-ß1 +869T>C was associated with a decreased risk for corpus-affected AGIM (adjusted odds ratio: 0.42, 95% confidence interval: 0.19-0.93, P = 0.032). The dominant inheritance models no revealed significant association for IFN-γ +874T>A, TNF-α-308G>A and IL-6 -174C>G gene polymorphism and the risk of localization of AGIM. Conclusion: TGF-ß1 +869T>C gene polymorphism is associated with a decreased risk for corporeal localization of premalignant lesions, while IFN-γ +874T>A, TNF-α-308G>A and IL-6 -174C>G are not associated with the risk for AGIM in immunohistochemically H. pylori negative patients.

Romanian Guidelines for Nonpharmacological Therapy of IBS.

BACKGROUND AND AIMS: The nonpharmacological therapy in irritable bowel syndrome (IBS) is expanding rapidly. Practitioners and medical educators need to be aware of progress and changes in knowledge of this topic. The Romanian Society of Neurogastroenterology aimed to create guidelines based on best evidence on the use of nonpharmacological therapy in IBS. METHODS: A group of experts was constituted. This was divided in eleven subgroups dedicated to eleven categories of nonpharmacological therapy. The subgroups searched the literature and formulated statements and recommendations. These were submitted to vote in order to obtain consensus. RESULTS: The outcome of this activity is represented by the guidelines of the Romanian Society of Neurogastroenterology, presented in this paper. The recommendations are seen as complementary to the pharmacological therapy and are not intended to recommend avoiding pharmacological drugs. CONCLUSIONS: These guidelines were elaborated by a Delphi process and represent a useful tool for physicians managing patients with IBS.

Helicobacter pylori infection over bile reflux: No influence on the severity of endoscopic or premalignant gastric lesion development.

Helicobacter (H.) pylori infection and duodenogastric reflux (DGR) are both linked to endoscopic and premalignant gastric lesion development, but it is still unclear whether they are independent or have a causal relationship. This study investigated the histologic gastric changes in patients with primary DGR and H. pylori infection, as well as their endoscopic findings, symptoms, drug consumption, and social behavior in comparison with patients presenting only DGR. The study included 560 patients with primary DGR on endoscopy divided into two groups, according to the presence/absence of H. pylori infection on biopsy (utilizing usual stainings and immunohistochemical methods). There was no significant difference in terms of age and sex, nor in the frequency of diabetes or esophagitis between the studied groups. Epigastric pain was associated with H. pylori-positive biopsies in multivariate logistic regression analysis (P=0.005). Although without statistical significance, severe endoscopic lesions and premalignant gastric lesions were more frequent in the H. pylori group (45.1 vs. 28.4% and 37.4 vs. 32.3%, respectively). In patients with DGR, the final multivariate model revealed a positive association between smoking and immunohistochemically confirmed H. pylori infection (P=0.02, OR=1.88, 95% confidence intervals (CI)=1.10 to 3.21), but a negative effect of proton pump inhibitor consumption (P<0.001, OR=0.50, 95% CI=0.35 to 0.73). In conclusion, in patients with H. pylori infection and DGR, epigastric pain was the main reason for the endoscopic investigation. H. pylori infection over DGR did not influence the severity of endoscopic or premalignant gastric lesion development. Furthermore, smoking is directly related to immunohistochemically assessed active H. pylori infection in patients with bile reflux.

Helicobacter pylori and cytokine gene variants as predictors of premalignant gastric lesions.

Gastric cancer remains the third leading cause of mortality from cancer worldwide and carries a poor prognosis, due largely to late diagnosis. The importance of the interaction between Helicobacter pylori (H. pylori) infection, the main risk factor, and host-related genetic factors has been studied intensively in recent years. The genetic predisposition for non-hereditary gastric cancer is difficult to assess, as neither the real prevalence of premalignant gastric lesions in various populations nor the environmental risk factors for cancer progression are clearly defined. For non-cardiac intestinal-type cancer, identifying the factors that modulate the progression from inflammation toward cancer is crucial in order to develop preventive strategies. The role of cytokines and their gene variants has been questioned in regard to non-self-limiting H. pylori gastritis and its evolution to gastric atrophy and intestinal metaplasia; the literature now includes various and non-conclusive results on this topic. The influence of the majority of cytokine single nucleotide polymorphisms has been investigated for gastric cancer but not for preneoplastic gastric lesions. Among the investigated gene variants onlyIL10T-819C, IL-8-251, IL-18RAP917997, IL-22 rs1179251, IL1-B-511, IL1-B-3954, IL4R-398 and IL1RN were identified as predictors for premalignant gastric lesions risk. One of the most important limiting factors is the inhomogeneity of the studies (e.g., the lack of data on concomitant H. pylori infection, methods used to assess preneoplastic lesions, and source population). Testing the modifying effect of H. pylori infection upon the relationship between cytokine gene variants and premalignant gastric lesions, or even testing the interaction between H. pylori and cytokine gene variants in multivariable models adjusted for potential covariates, could increase generalizability of results.

Factors Associated with Recurrent Ulcers in Patients with Gastric Surgery after More Than 15 Years: A Cross-Sectional Single-Center Study.

AIM: We aimed to establish the independent predictive factors (from Helicobacter pylori infection, biliary reflux, histologic features of the gastric mucosa, drugs, comorbidities, and social habits) for gastric stump ulcer occurrence more than 15 years after surgery. METHODS: 76 patients with previous gastric surgery were included: 21 patients with gastric ulcer (marginal ulcer or ulcer of the rest of the gastric remnant-study group) and 55 controls (nonulcer group). RESULTS: Helicobacter pylori infection tended to be higher in the control group than in the ulcer group (14.5% vs. 4.8%, p = 0.43), without statistical significance. Alcohol consumption had a significant positive association with ulcer (p = 0.008), while smoking (p = 0.064), low-dose aspirin (p = 0.063), and biliary reflux (p = 0.106) had a tendency toward statistical signification for positive association. On univariate analysis, smoking (p = 0.048, OR = 3.15, 95% CI: 1.01-9.93) and low-dose aspirin consumption (p = 0.067, OR = 2.63, 95% CI: 0.95-7.68) were significantly associated with ulcer. According to the multivariable regression model, alcohol consumption (OR = 6.68, 95% CI: 1.29-41.14) and biliary reflux (OR = 6.12, 95% CI: 1.36-38.26) remained significantly associated with increased odds of stump ulcer. CONCLUSION: Biliary reflux and alcohol consumption, but not Helicobacter pylori infection or gastrotoxic drug, seem to be the most important predictors for ulcer recurrence in patients with gastric surgery for peptic ulcer after more than 15 years.

The CAT-262 C>T, MnSOD Ala16Val, GPX1 Pro198Leu Polymorphisms Related to Oxidative Stress and the Presence of Gastric Lesions.

BACKGROUND AND AIMS: The increased oxidative stress plays an important role in gastro-duodenal ulcers and gastric cancer occurrence. We investigated the association between the genetic polymorphisms of genes encoding the antioxidative enzymes CAT, GPX and SOD and the occurrence of gastric lesions, considering also the environmental risk factors such as H. pylori infection, drug exposure, smoking and alcohol consumption. METHODS: We included 373 patients who underwent endoscopy for symptoms, anemia or bleeding investigation. A complete set of demographical, clinical and pathological data was recorded. All patients were successfully genotyped. RESULTS: In the multivariate logistic regression model, the patients having Pro/Pro genotype of GPX1 gene polymorphism had more severe gastric lesions as compared with patients with the Leu/Pro or Leu/Leu genotype (OR= 1.89, 95%CI: 0.99-3.57, p=0.051). The GPX1 Pro198Leu and the MnSOD Ala16Val gene polymorphism could be independent risk factors for reactive gastropathy changes, as shown by their association very close to statistical significance (p=0.059 and p=0.054, respectively). Consumption of anticoagulants was a significant independent predictor (p=0.023, OR:0.43 95%CI:0.21-0.89) for the absence of active gastritis, while low-dose aspirin consumption was a risk factor for active gastritis in biopsy samples (p=0.025, OR:1.71, 95%CI:1.07-2.74). CONCLUSION: The variant genotype of GPX1Pro198Leu was associated with an increased risk for reactive gastropathy changes in gastric biopsies and with less severe endoscopic lesions, while MnSODAla16Val variant genotype (Val/Val or Val/Ala) seems to be related to the reactive gastropathy. However, none of them were associated with inflammatory or premalignant gastric lesions.

Statins and gastroduodenal endoscopic lesions: A case-control study.

Experimental studies showed a dose-dependent gastroprotective effect of statins on non-steroidal anti-inflammatory drug-induced endoscopic lesions, modulated by increasing endogenous nitric oxide and prostaglandin production.We investigated the influence of chronic treatment with statins on the occurrence of endoscopic lesions in patients referred for endoscopic evaluation, adjusted for the most important etiologic and risk factors for peptic ulcer disease and its complications.A consecutive series of 564 patients who underwent upper digestive endoscopy, stratified according to the severity of endoscopic lesions were recruited. Patients with statin therapy were included in the study group (n = 220), while patients without statins in the control group (n = 344). We correlate the influence of chronic statin therapy (at least 6 months) with factors including age up to 50 years, Helicobacter pylori infection, smoking and drinking habits, ulcer history, gastrotoxic drug consumption (low-dose aspirin [ASA], anticoagulants), and comorbidities.H pylori infection was more frequent in patients with mild/severe endoscopic lesions vs. no lesions, in both groups, but the difference was not statistically significant (P >.05). Male gender represented a risk factor (P <.01) for mild/severe endoscopic lesions only in the statin group. The estimated risk for developing mild/severe endoscopic lesions with ASA intake decreased from 6.26 to 3.40 (P <.01) when statin therapy was associated. Patients without statins and ischemic coronary artery disease (P <.01; odds ratio [OR] = 2.99; 95% confidence interval (CI):1.88-4.73), heart failure (P = .01; OR = 2.13; 95% CI:1.36-3.34), systemic atherosclerosis (P = .04; OR = 2.30; 95% CI:1.44-3.67) had a statistically significant increased risk for developing mild/severe endoscopic lesions in comparison with patients in the statin group. In multivariate regression analysis models, smoking (P <.01; OR = 2.69; 95% CI:1.73-4.16), ASA (P <.01; OR = 4.54; 95% CI:2.83-7.16), and coronary artery diseases (P = .01; OR = 1.80; 95% CI:1.15-2.82) were independent risk factors for mild/severe endoscopic lesions, while chronic statin therapy (P <.01; OR = 0.31; 95% CI:0.19-0.51) was associated with a protective effect in all models.The results of the present study support a certain protective role of chronic therapy with statins against endoscopic lesions, especially in ASA consumers or patients with cardiovascular diseases.

The contribution of clinical and pathological predisposing factors to severe gastro-duodenal lesions in patients with long-term low-dose aspirin and proton pump inhibitor therapy.

BACKGROUND: Preventive strategies developed to avoid the complications of antiplatelet therapies recommend the evaluation of risk factors for gastrointestinal events and indicated gastroprotective strategies. AIM: We aimed to assess the impact of predisposing factors - histological findings, concomitant drug consumption, comorbidities, symptoms, social habits, Helicobacter pylori infection - on severe gastro-duodenal lesions in patients with low-dose aspirin and concomitant protective therapy with proton pump inhibitors (PPI). METHOD: We enrolled 237 patients with LDA and PPI therapy, referred for upper digestive endoscopy, divided into two groups according to the severity of their endoscopic lesions (172 patients with no or mild endoscopic lesions and 65 patients with severe endoscopic lesions). RESULTS: In the univariate logistic regression model, the factors associated with severe gastro-duodenal lesions were gender (OR=1.87, 95% CI: 1.04-3.41), anticoagulants (OR=2.40, 95% CI: 1.26-4.53), gastric atrophy and/or intestinal metaplasia (OR=1.85, 95% CI: 1.04-3.32), congestive heart failure (OR=2.59, 95% CI: 1.16-6.62), anaemia (OR=3.01, 95% CI: 1.67-5.47) and smoking (OR=4.29, 95% CI: 1.57-12.32). In the final model, anticoagulants (p=0.041<0.05) and anaemia (p=0.019<0.05) were risk factors for severe lesions via multivariate regression analysis, while for active/inactive chronic gastritis and smoking a positive dependency with a tendency towards statistical significance (p<0.10) was noticed for severe gastric lesions. CONCLUSIONS: In patients treated with low-dose aspirin and gastroprotective therapy with proton pump inhibitors we have enough evidence to consider co-treatment with anticoagulants and anaemia important predictors for severe endoscopic lesions, while other factors such as inflammation in gastric biopsies, congestive heart failure, co-treatment with clopidogrel and smoking tended to have a positive influence on risk for severe gastro-duodenal lesions.

The Interaction between GSTT1, GSTM1, and GSTP1 Ile105Val Gene Polymorphisms and Environmental Risk Factors in Premalignant Gastric Lesions Risk.

The study investigated the possible influence of GSTM1, GSTT1, and GSTP1 gene polymorphisms as predisposing factors for premalignant gastric lesions as well as their interaction with H. pylori infection, gastrotoxic drugs, smoking, and alcohol consumption. In this study, 270 patients with a complet set of gastric biopsies and successfully genotyped were finally included. The GSTM1 gene polymorphism had significant contribution in mild/severe endoscopic lesions (p = 0.01) as well as in premalignant lesions (p = 0.01). The GSTM1 null genotype increased the risk for mucosal defects in H. pylori-negative patients (OR = 2.27, 95% CI: 1.20-4.37) and the risk for premalignant lesions in patients with no alcohol consumption (OR = 2.13, 95% CI: 1.19-3.83). The GSTT1 deleted polymorphism did not significantly increase the risk for premalignant lesions in the absence of gastrotoxic drugs (OR = 1.82, 95% CI: 0.72-4.74). The combined GSTT1T1 and GSTM1 null polymorphisms were borderline correlated with an increased risk for premalignant lesions (OR = 1.72, 95% CI: 1.00-2.97). The wild-type GSTP1 Ile/Ile genotype versus the variant genotypes Ile/Val + Val/Val was significantly associated with a decreased risk of gastric atrophy/intestinal metaplasia (OR = 0.60, 95% CI: 0.37-0.98). In conclusion, the GSTM1 and GSTT1 null genotypes increased the risk for premalignant and endoscopic gastric lesions, modulated by H. pylori, alcohol, or gastrotoxic drug consumption, while the presence of the GSTP1Val allele seemed to reduce the risk for premalignant lesions.

Clinical Risk Factors for Gastroduodenal Ulcer in Romanian Low-Dose Aspirin Consumers.

Background. Aspirin use for cardiovascular or cancer prevention is limited due to its gastrointestinal side effects. Objective. Our prospective, observational case-control study aims to identify the predictive factors for ulcers in low-dose aspirin consumers (75-325 mg/day). Methods. The study included patients who underwent an upper digestive endoscopy and took low-dose aspirin treatment. Results. We recruited 51 patients with ulcer (ulcer group) and 108 patients with no mucosal lesions (control group). In univariate analysis, factors significantly associated with ulcers were male gender (p = 0.001), anticoagulants (p = 0.029), nonsteroidal anti-inflammatory drugs (p = 0.013), heart failure (p = 0.007), liver (p = 0.011) or cerebrovascular disease (p = 0.004), diabetes mellitus (p = 0.043), ulcer history (p = 0.044), and alcohol consumption (p = 0.018), but not Helicobacter pylori infection (p = 0.2). According to our multivariate regression analysis results, history of peptic ulcer (OR 3.07, 95% CI 1.06-8.86), cotreatment with NSAIDs (OR 8, 95% CI 2.09-30.58) or anticoagulants (OR 4.85, 95% CI 1.33-17.68), male gender (OR 5.2, 95% CI 1.77-15.34), and stroke (OR 7.27, 95% CI 1.40-37.74) remained predictors for ulcer on endoscopy. Conclusions. Concomitant use of NSAIDs or anticoagulants, comorbidities (cerebrovascular disease), and male gender are the most important independent risk factors for ulcer on endoscopy in low-dose aspirin consumers, in a population with a high prevalence of H. pylori infection.