Effects of long-term cyclo-oxygenase 2 selective and acid inhibition on Barrett's oesophagus.

BACKGROUND: There is an overexpression of cyclo-oxygenase 2 (COX-2) in Barrett's oesophagus (BO). AIM: To determine the long-term effect of a COX-2 inhibitor on cellular mechanisms involved in BO. METHODS: A randomized controlled trial was conducted in BO patients allocated to continue the usual proton pump inhibitor (PPI) alone treatment, or PPI combined with rofecoxib (25 mg/day) for 6 months. Cell proliferation index and COX-2 expression in BO glands was determined in biopsy specimens at baseline and after treatment. Cell apoptosis, cyclin D1, p53 and vascular endothelial growth factor (VEGF) expression was also explored in a subset of patients. Student-t test and the U-Mann-Whitney test were used for quantitative and ordinal variables. RESULTS: Of 62 patients, 58 completed the study. A higher proportion of patients on rofecoxib + PPI exhibited a decrease in COX-2 expression compared to those treated with PPI alone, but cell proliferation index was not affected. Unlike PPI alone, rofecoxib + PPI was associated with an increase in the apoptotic cell index, a decrease in p53 cell staining and VEGF expression in mucosal vessels. No effect on low-grade dysplasia or cyclin D1 was observed. CONCLUSIONS: The addition of rofecoxib to PPI therapy does not affect cell proliferation index in BO cells after 6 months of therapy, but does reduce COX-2 and VEGF expression and increases cell apoptosis.

Helicobacter pylori increases the risk of upper gastrointestinal bleeding in patients taking low-dose aspirin.

AIM: To evaluate the role of Helicobacter pylori infection and other clinical factors in the risk of upper gastrointestinal bleeding in patients taking low-dose aspirin. SUBJECTS AND METHODS: A case-control study was carried out of consecutive current users of low-dose aspirin admitted because of upper gastrointestinal bleeding. Within a cohort of 695 patients with upper gastrointestinal bleeding, 98 patients had taken low-dose aspirin and no other non-steroidal anti-inflammatory drug. Controls were 147 low-dose aspirin users without upper gastrointestinal bleeding of similar age, sex and extent of aspirin use as cases. H. pylori infection was determined by CagA/VacA serology and 13C-urea breath test in all cases and controls. Adjusted odds ratios (OR) are provided. RESULTS: H. pylori infection was identified as an independent risk factor of upper gastrointestinal bleeding in this population (OR, 4.7; 95% confidence interval (95% CI), 2.0-10.9), but the presence of CagA-positive serology was not. Other risk factors identified were a previous ulcer history (OR, 15.2; 95% CI, 3.8-60.1), alcohol use (OR, 4.2; 95% CI, 1.7-10.4) and use of calcium channel blockers (OR, 2.54; 95% CI, 1.25-5.14). Antisecretory therapy (OR, 0.1; 95% CI, 0.02-0.3) and nitrovasodilators (OR, 0.2; 95% CI, 0.1-0.6) decreased the risk of bleeding. CONCLUSIONS: H. pylori infection is a risk factor for upper gastrointestinal bleeding in low-dose aspirin users, which might have therapeutic implications in high-risk patients.

Effects of nitrate and prophylactic aspirin on upper gastrointestinal bleeding: a retrospective case-control study.

Experimental studies suggest that nitric-oxide releasing drugs reduce gastroduodenal damage induced by non-steroidal anti-inflammatory drugs, but it is not known whether these agents have this effect in humans. The aim of the present study was to evaluate the risk of upper gastrointestinal bleeding in patients who receive aspirin and nitrates for vascular occlusive diseases. This was a retrospective case-control study of 736 consecutive patients admitted with upper gastrointestinal bleeding, compared with 1472 age- and sex-matched hospital controls. Chronic low-dose aspirin regimens had been used by 12.6% of cases and 5.7% of controls, nitrates by 4.8% and 5.8%, and combined nitrates and low-dose aspirin by 2.7% and 1.9%, respectively. Logistic regression analysis identified low-dose aspirin use as an independent risk factor for gastrointestinal bleeding, whereas nitrate use was found to be a protective factor. The combination of both nitrate and low-dose aspirin was not associated with an increased risk of bleeding.

[Omeprazole and cimetidine in the treatment of upper digestive hemorrhage]. / Omeprazol y cimetidina en el tratamiento de la hemorragia digestiva alta.

AIM: To compare the efficacy of omeprazole (40 mgs/12 h i.v.) and cimetidine (1,200 mgs/i.v./day) in the management of upper gastrointestinal bleeding. EXPERIMENTAL DESIGN: Randomized, prospective open clinical trial. The end points are: mortality, surgical requirements, transfusion requirements, and length of hospitalization in Bleeding Unit and Hospital. PATIENTS: We study patients with upper gastrointestinal bleeding from peptic sources (duodenal ulcer, gastriculcer, acute gastric erosions and peptic esophagitis). 462 patients are evaluated and 282 finally included. RESULTS: 151 patients were given cimetidine and 131 omeprazole. No significant differences in any of the end points were found. CONCLUSIONS: The use of omeprazole does not improve cimetidine efficacy in the entire group of patients with upper gastrointestinal bleeding.

[The endoscopic management of postoperative biliary fistulae]. / Manejo endoscópico de las fístulas biliares postquirúrgicas.

We report a series of 15 patients with a postoperative biliary fistula treated by endoscopic sphincterotomy. The exact location of the bile leak was revealed by ERCP in 13 cases (87%): cystic duct remnant in 6 (39%), intrahepatic biliary tree in 4 (26%), and main bile duct in 3 (20%). In all cases a distal obstacle (ie: retained stones, hydatid material) to bile flow was also found in ERCP. Treatment consisted of endoscopic sphincterotomy and subsequent removal of the distal obstacle, and could be completed in 13 (87%) cases. In our experience the treatment of postoperative biliary fistula with a distal obstruction bile flow by endoscopic sphincterotomy is a safe and effective procedure, and should be recommended as the first option in those patients.

Evidence of aspirin use in both upper and lower gastrointestinal perforation.

BACKGROUND & AIMS: Current studies lack appropriate data on aspirin and other risk factors for gastrointestinal perforation. The aim of this study was to obtain the best estimate on aspirin and nonaspirin nonsteroidal anti-inflammatory drug (NSAID) use in these patients. METHODS: In 76 consecutive patients with gastrointestinal perforation and 152 matched controls, a detailed clinical history supplemented with an objective test of current aspirin use (platelet cyclooxygenase activity) was obtained. RESULTS: Of the 76 cases, 78.9% were upper and 21% lower gastrointestinal perforations. Evidence of NSAID use was found in 71% of cases (70% upper, 75% lower) vs. 26.9% of controls (odds ratio, 6.64; 95% confidence interval, 3.6-12.2; P < 0.0001). The objective test showed 12.7% more aspirin users than clinical history alone. NSAID use was aspirin (alone or combined) in 66.6% of cases, and 59.25% was nonprescription. Other independent risk factors were smoking, alcohol, and a history of arthritis or peptic ulcer but not a positive Helicobacter pylori serology. Age, but not NSAID use, affected perforation-associated mortality. CONCLUSIONS: NSAID use is strongly associated with an increased risk of both upper and lower gastrointestinal perforation. The high prevalence of aspirin (over-the-counter) use suggests that future introduction of new NSAIDs may not have a major impact on decreasing gastrointestinal complications if other measures are not taken. Concomitant NSAID use, smoking, and alcohol use is a pervasive association.

Nitrovasodilators, low-dose aspirin, other nonsteroidal antiinflammatory drugs, and the risk of upper gastrointestinal bleeding.

UNLABELLED: BACKGROUND The relation between medications that release nitric oxide, such as nitroglycerin and other nitrovasodilators, and upper gastrointestinal bleeding is uncertain. In animals, these medications reduce the gastric damage induced by nonsteroidal antiinflammatory drugs. Nitric oxide, however, inhibits platelet aggregation and may contribute to bleeding from an ulcer. METHODS: We performed a case-control study to determine the risk of bleeding in patients taking nitrovasodilators, low-dose aspirin, or other nonsteroidal antiinflammatory drugs. The case group was made up of 1122 consecutive patients admitted to one of four hospitals with bleeding from a peptic lesion. The 2231 control subjects were 1109 patients hospitalized for other reasons and 1122 outpatients from the same geographic area. RESULTS: In the week before admission, 520 (46.3 percent) of the patients with bleeding had taken a nonsteroidal antiinflammatory drug other than low-dose aspirin, 120 (10.7 percent) had taken low-dose aspirin (< or = 300 mg per day), 60 (5.3 percent) a nitrovasodilator, and 135 (12.0 percent) an antisecretory agent such as a histamine H2-receptor antagonist or a proton-pump inhibitor. In multivariate models that adjusted for age, sex, and clinical risk factors, the use of a nonsteroidal antiinflammatory drug other than low-dose aspirin was independently associated with an increased risk of bleeding from a peptic ulcer (odds ratio, 7.4; 95 percent confidence interval, 4.5 to 12.0), as was the use of low-dose aspirin alone (odds ratio, 2.4; 95 percent confidence interval, 1.8 to 3.3). The use of a nitrovasodilator was associated with a decreased risk of bleeding (odds ratio, 0.6; 95 percent confidence interval, 0.4 to 0.9), as was antisecretory therapy (odds ratio, 0.6; 95 percent confidence interval, 0.4 to 0.8). In patients taking any type of nonsteroidai antiinflammatory drug, the use of a nitrovasodilator or antisecretory therapy was independently associated with a decreased risk of bleeding. CONCLUSIONS: The use of nitrovasodilator drugs is independently associated with a decreased risk of upper gastrointestinal bleeding.

Low frequency of upper gastrointestinal complications in a cohort of high-risk patients taking low-dose aspirin or NSAIDS and omeprazole.

BACKGROUND: There is very little information available on the incidence of complications and on the best prevention therapy in high-risk patients taking non-steroidal anti-inflammatory drugs (NSAIDs) and/or aspirin. Randomized-controlled trials in such patients are rare for ethical reasons. We studied the incidence of gastrointestinal complications in high-risk patients taking long-term low-dose aspirin or non-aspirin-NSAIDs combined with omeprazole in a real-life clinical setting. METHODS: This was a multicentre, prospective and observational study including 247 consecutive high-risk patients who had a clinical indication for long-term treatment with either low-dose aspirin or non-aspirin NSAIDs and omeprazole therapy. The occurrence of gastrointestinal complications was measured. RESULTS: In addition to a recent history of peptic ulcer bleeding, all patients had at least 1 other risk factor and 112 (45.3%) had 3 or more risk factors; 78.9% were taking low-dose aspirin and the remainder non-aspirin NSAIDs. Mean follow-up was 14.6 +/- 10.38 months. Three patients taking low-dose aspirin developed upper gastrointestinal bleeding (1.2%; 95% CI 0.3-3.5; 1.0 event/100 patients/year). This was similar to the rate observed in studies involving non-high-risk patients taking low-dose aspirin and higher than that observed in patients not taking low-dose aspirin. Two additional patients developed a lower gastrointestinal bleeding event (0.81% (0.04%-3.12%); 0.67 events/100 patients/year), which was within the range expected in NSAID users. CONCLUSIONS: The use of omeprazole in the high-risk patient taking low-dose aspirin or NSAIDs seems to be a safe therapeutic approach in this population and is associated with a low frequency of upper gastrointestinal complications.