s-1743 and Metaplasia

As the relative efficacy of therapeutic agents in the treatment of gastro-oesophageal reflux disease is related to how consistently and completely gastric acid secretion is suppressed, intragastric pH monitoring is a useful tool in stratifying therapies. If there is no acid in the stomach, there can be none to reflux into the oesophagus. Comparative crossover studies have shown consistently that once-daily esomeprazole (40 mg) provides more effective and longer lasting intragastric acid control than any other proton pump inhibitor currently available in healthy subjects and patients with gastro-oesophageal reflux disease. However, esomeprazole maintained intragastric pH > 4 for > or = 16 h in only about 55% of individuals tested. Thus, if more complete acid suppression is desirable, twice-daily proton pump inhibitor therapy may be advantageous. One such scenario is in patients with Barrett's metaplasia. Data from the ProGERD study suggest that, for each Los Angeles grade of oesophagitis, the healing rate for patients with Barrett's metaplasia is 10-30% less than that for non-Barrett's patients, being as low as 53% in patients with Los Angeles grade D oesophagitis. Also relevant to the Barrett's metaplasia population are studies on the oesophageal mucosa, which show that effective acid suppression favours differentiation and decreases epithelial cell proliferation. Both considerations argue for more intensive gastric acid inhibition than can be achieved with once-daily therapy, leading to experimentation with twice-daily proton pump inhibitor regimens. A randomized, double-blind, three-way crossover study compared esomeprazole 40 mg once daily with esomeprazole 20 mg and 40 mg twice daily and found that both twice-daily regimens were superior, maintaining intragastric pH > 4 for 73%[95% confidence interval (CI), 67-79%] and 80% (95% CI, 75-86%) of the day, respectively, compared with 59% (95% CI, 54-65%) of the day with esomeprazole 40 mg once daily, arguing that a twice-daily regimen may be the preferred strategy for patients with Barrett's metaplasia.

Topics: Anti-Ulcer Agents; Barrett Esophagus; Esomeprazole; Esophagus; Gastric Acid; Gastroesophageal Reflux; Humans; Hydrogen-Ion Concentration; Metaplasia; Proton Pump Inhibitors; Randomized Controlled Trials as Topic

We aimed to evaluate the effectiveness and safety of bismuth-containing quadruple therapy plus postural change after dosing for Helicobacter pylori eradication in gastrectomized patients. We compared 76 gastric stump patients with H. pylori infection (GS group) with 50 non-gastrectomized H. pylori-positive patients who met the treatment indication (controls). The GS group was divided into GS group 1 and GS group 2. All groups were administered bismuth potassium citrate (220 mg), esomeprazole (20 mg), amoxicillin (1.0 g), and furazolidone (100 mg) twice daily for 14 days. GS group 1 maintained a left lateral horizontal position for 30 min after dosing. H. pylori was detected using rapid urease testing and histologic examination of gastric mucosa before and 3 months after therapy. Mucosal histologic manifestations were evaluated using visual analog scales of the updated Sydney System. GS group 1 had a higher prevalence of eradication than the GS group 2 (intention-to-treat [ITT]: P=0.025; per-protocol [PP]: P=0.030), and the control group had a similar prevalence. GS group 2 had a lower prevalence of eradication than controls (ITT: P=0.006; PP: P=0.626). Scores for chronic inflammation and activity declined significantly (P<0.001) 3 months after treatment, whereas those for atrophy and intestinal metaplasia showed no significant change. Prevalence of adverse reactions was similar among groups during therapy (P=0.939). A bismuth-containing quadruple therapy regimen plus postural change after dosing appears to be a relatively safe, effective, economical, and practical method for H. pylori eradication in gastrectomized patients.

Topics: Adult; Aged; Aged, 80 and over; Amoxicillin; Anti-Bacterial Agents; Anti-Ulcer Agents; Drug Therapy, Combination; Esomeprazole; Female; Furazolidone; Gastrectomy; Gastric Stump; Helicobacter Infections; Helicobacter pylori; Humans; Male; Metaplasia; Middle Aged; Organometallic Compounds; Patient Positioning; Potassium Citrate; Treatment Outcome; Young Adult

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

The aim of this study was to determine the effect of 6-12 months of treatment with esomeprazole on the histopathology of the gastric mucosa.. Two identically designed, randomized, placebo-controlled trials of esomeprazole 40, 20, or 10 mg daily for up to 6 months, as well as a noncomparative, multicenter trial of esomeprazole 40 mg daily for up to 12 months, were conducted in 1326 patients with healed erosive esophagitis (1294 negative for Helicobacter pylori [H. pylori]). Gastric biopsy samples were obtained before treatment and on completion of (or discontinuation from) the trials. Samples were evaluated for the presence of H. pylori, characteristics of acute gastritis or atrophic gastritis, and enterochromaffin-like cell pathology.. During treatment with esomeprazole, the number of patients with an improvement in gastric histological scores was typically greater than or equal to the number who worsened. Gastric histological scores worsened for each corporal or antral characteristic of gastritis in <6.2% of patients. Histological scores with esomeprazole and placebo were similar throughout the 6-month trials. Only one among 1326 patients treated with esomeprazole (H. pylori negative) had evidence of treatment-emergent atrophic gastritis. On final biopsy, 5-12% of patients had abnormal enterochromaffin-like cell scores (simple, linear, or micronodular hyperplasia). There were no instances of enterochromaffin-like cell dysplasia, carcinoids, or neoplasia.. Patients with healed erosive esophagitis receiving esomeprazole for up to 12 months had minor fluctuations in gastric histological scores, similar to those experienced in untreated populations. Use of esomeprazole did not raise any safety concerns with respect to the development of atrophic gastritis, or cause clinically significant changes in enterochromaffin-like cells.

Topics: Adult; Anti-Ulcer Agents; Enterochromaffin-like Cells; Esomeprazole; Esophagitis; Gastric Mucosa; Gastrins; Gastritis, Atrophic; Helicobacter Infections; Helicobacter pylori; Humans; Metaplasia

Histological Barrett's esophagus, defined as specialized intestinal metaplasia (SIM+) at the cardia without endoscopic suspicion of columnar epithelium, is found frequently in biopsies at the gastro-esophageal junction although its clinical relevance is unknown. The authors aim was to evaluate prospectively the progression of SIM+ to macroscopically evident Barrett's esophagus (BE/SIM+), and to identify risk factors for this progression.. Data were obtained from a sub-group of patients (no visible BE at presentation, but SIM+) included in the ProGERD study, a prospective evaluation of the clinical course of GERD under routine clinical care. They had esomeprazole 20-40 mg/day for 2-8 weeks. Symptom assessment was performed annually, and endoscopy with biopsy was planned at baseline, after healing treatment and after 2 and/or 5 years.. 128 of 171 (74.8%) patients with unequivocal SIM at the z-line after healing were biopsied again after 2 and/or 5 years. At follow-up, 33 (25.8%) of these patients showed progression to BE/SIM+. Factors significantly associated with progression were smoking, a long history of GERD and severe esophagitis at baseline. Patients who had progressed to BE/SIM+ already at 2 years showed consistent findings at 5 years.. More than 20% of GERD patients with SIM+ in this study were found to have BE/SIM+ within 2-5 years. This finding supports the hypothesis that SIM+ at the cardia could be the missing link explaining increased cancer risk in GERD patients without overt BE and merits further investigation in a prospective study.

Topics: Adult; Aged; Barrett Esophagus; Biopsy; Cardia; Confidence Intervals; Endoscopy, Gastrointestinal; Esomeprazole; Esophagitis; Esophagogastric Junction; Female; Follow-Up Studies; Gastroesophageal Reflux; Humans; Male; Metaplasia; Middle Aged; Odds Ratio; Prospective Studies; Proton Pump Inhibitors; Smoking; Time Factors