s-1743 and Precancerous-Conditions

Patients with dysplasia in Barrett's esophagus (BE) have a considerable risk of developing esophageal adenocarcinoma (EAC). The mucosal expression of the pro-inflammatory angiotensin II receptor type 1 (AT1R) is elevated in these patients, suggesting a role in carcinogenesis. The purpose of this study was to determine whether interference with the renin-angiotensin system (RAS) would influence downstream markers of carcinogenesis.. Endoscopic mucosal biopsies from BE patients with low-grade dysplasia (LGD) were sampled before and after a three-week period of RAS-interfering treatment. Thirty patients were randomly allocated to enalapril (ACE inhibitor, 5 mg od), candesartan (AT1R antagonist, 8 mg od), or no drug. The expression of 12 proteins known to be associated with RAS and carcinogenesis was assessed using western blot.. We found altered expression of several proteins after enalapril treatment (decreased: NFκB, p = .043; NLRP3, p = .050; AMACR, p = .017; and caspase 3, p = .025; increased: p53, p = .050). Candesartan treatment was associated with increased iNOS expression (p = .033). No significant changes were seen in the no-drug group.. Interference with angiotensin II formation was associated with altered expression of inflammation- and carcinogenesis-related proteins. The present results speak in favor of involvement of angiotensin II in BE dysplasia, but the role of AT1R should be investigated further.

Topics: Adenocarcinoma; Adult; Aged; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Barrett Esophagus; Benzimidazoles; Biomarkers, Tumor; Biphenyl Compounds; Enalapril; Endoscopy; Esomeprazole; Esophageal Neoplasms; Female; Humans; Hyperplasia; Male; Middle Aged; Neoplasm Proteins; Nitric Oxide Synthase Type II; Precancerous Conditions; Prospective Studies; Proton Pump Inhibitors; Renin-Angiotensin System; Risk Factors; Sweden; Tertiary Care Centers; Tetrazoles

This study aimed to determine whether Helicobacter pylori eradication limits the progression of precancerous changes, manifested as intestinal metaplasia (IM), in patients with reflux esophagitis using long-term esomeprazole.. Three hundred twenty-five reflux esophagitis patients were enrolled and randomly assigned to (i) the H. pylori-positive eradication group receiving 1-week triple therapy (n=105); (ii) H. pylori-positive non-eradication controls (n=105); and (iii) H. pylori-negative controls (n=115). All the patients received continuous esomeprazole until sustained symptomatic response, and when possible, shifted to on-demand therapy (ODT) thereafter. Serial gastroscopy was scheduled on enrollment and at the end of the first and second years to assess the prevalence and progression or regression of gastric atrophy (AT) and IM.. There were 93 patients in the H. pylori-eradication group, 83 in the non-eradication controls, and 100 in the negative controls to complete the study. The negative controls had no progression of AT and IM during follow-up. For the H. pylori-positive eradication group, there was significant regression of AT and IM during follow-up (P<0.05). In the H. pylori-positive non-treated controls, the prevalence rates of AT and IM were significantly greater on the second year than on enrollment (P<0.05). During the second-year follow-up, the patients in the eradication group achieved more regression and less development of AT and IM than did the non-eradication controls (P<0.001).. In patients using long-term esomeprazole for reflux esophagitis, screening for and eradicating H. pylori infection are necessary in order to limit the progression or cause the regression of gastric precancerous changes.

Topics: Adult; Analysis of Variance; Anti-Ulcer Agents; Biopsy, Needle; Confidence Intervals; Disease Progression; Dose-Response Relationship, Drug; Drug Administration Schedule; Esomeprazole; Esophagitis, Peptic; Esophagoscopy; Female; Follow-Up Studies; Gastroscopy; Helicobacter Infections; Helicobacter pylori; Humans; Immunohistochemistry; Intestinal Neoplasms; Long-Term Care; Male; Metaplasia; Middle Aged; Odds Ratio; Precancerous Conditions; Probability; Stomach; Stomach Neoplasms; Treatment Outcome