Echocardiographic examination of women previously treated with fenfluramine: long-term follow-up of a randomized, double-blind, placebo-controlled trial.

BACKGROUND: Fenfluramine hydrochloride was withdrawn from the market in September 1997 after reports of heart valve abnormalities in patients who used it. The prevalence of echocardiographic abnormalities and the clinical cardiovascular status of patients who received fenfluramine monotherapy remains uncertain. METHODS: A long-term, follow-up evaluation was undertaken in subjects who were randomly assigned to receive either fenfluramine hydrochloride (60 mg daily) or placebo as part of a double-blind smoking cessation therapy study. Cardiovascular status was evaluated by echocardiography, medical history, and physical examination. RESULTS: From the group of 720 smokers who had originally participated in the smoking cessation therapy trial, 619 women were enrolled; data from 530 (276 in the fenfluramine group and 254 in the placebo group) were evaluable. No statistically significant differences were identified in the prevalence of aortic or mitral regurgitation by Food and Drug Administration criteria or by grade, aortic or mitral valve leaflet mobility restriction or thickening, elevated pulmonary artery systolic pressure, or abnormal left ventricular ejection fraction. No significant differences were demonstrated in cardiovascular status by physical examination, and no serious cardiac events were noted among fenfluramine-treated subjects. CONCLUSION: There was no evidence of drug-related heart disease up to 4.9 years after anorexigen therapy in subjects who were randomly assigned to receive fenfluramine at the recommended dose for up to 3 months.

Safety of a systematic endoscopic biopsy protocol in patients with Barrett's esophagus.

OBJECTIVE: Widespread implementation of rigorous, systematic endoscopic biopsy protocols for patients with Barrett's esophagus may be hindered by concerns about their safety. This report describes the safety experience of a large series of patients with gastroesophageal reflux disease and Barrett's esophagus who underwent such procedures. METHODS: Patients in the Seattle Barrett's Esophagus Project undergo biopsy surveillance in a research-based clinical setting, using large channel endoscopes and "jumbo" biopsy forceps. After visual inspection, multiple biopsies are obtained from lesions and at 1- to 2-cm intervals throughout the Barrett's esophageal segment. RESULTS: From 1983 to 1997, 1,458 consecutive endoscopies were performed on 705 patients and 50,833 biopsies (average, 35; maximum, 120 per procedure) were taken. Procedures lasted from 15 to 90 min during which one to two biopsies were obtained per minute. Eleven patients experienced 18 significant adverse events, five of which led to overnight hospitalizations: two for bleeding attributed to concomitant esophageal stricture dilation; two for cardiac dysrhythmias; and one for respiratory arrest. Events managed in outpatient settings included chest pain during seven endoscopies (all accounted for by two patients), chest or epigastric pain developing after five endoscopies, and one tonsillar abrasion. All patients recovered completely, and no deaths, perforations, aspiration, or esophageal stricturing resulted from the procedures. CONCLUSIONS: A rigorous, systematic endoscopic biopsy protocol in patients with Barrett's esophagus does not produce esophageal perforation or bleeding when performed by an experienced team of physicians, nurses, and technicians.

Effect of segment length on risk for neoplastic progression in patients with Barrett esophagus.

BACKGROUND: The increased risk for esophageal adenocarcinoma associated with long-segment (> or =3 cm) Barrett esophagus is well recognized. Recent studies suggest that short-segment (<3 cm) Barrett esophagus is substantially more common; however, the risk for neoplastic progression in patients with this disorder is largely unknown. OBJECTIVE: To examine the relation between segment length and risk for aneuploidy and esophageal adenocarcinoma in patients with Barrett esophagus. DESIGN: Prospective cohort study. SETTING: University medical center in Seattle, Washington. PATIENTS: 309 patients with Barrett esophagus. MEASUREMENTS: Patients were monitored for progression to aneuploidy and adenocarcinoma by repeated endoscopy with biopsy for an average of 3.8 years. Cox proportional hazards analysis was used to calculate adjusted relative risks and 95% Cls. RESULTS: After adjustment for histologic diagnosis at study entry, segment length was not related to risk for cancer in the full cohort (P > 0.2 for trend). When patients with high-grade dysplasia at baseline were excluded, however, a nonsignificant trend was observed; based on a linear model, a 5-cm difference in segment length was associated with a 1.7-fold (95% CI, 0.8-fold to 3.8-fold) increase in cancer risk. Among all eligible patients, a 5-cm difference in segment length was associated with a small increase in the risk for aneuploidy (relative risk, 1.4 [CI, 1.0 to 2.1]; P = 0.06 for trend). A similar trend was observed among patients without high-grade dysplasia at baseline. CONCLUSIONS: The risk for esophageal adenocarcinoma in patients with short-segment Barrett esophagus was not substantially lower than that in patients with longer segments. Although our results suggest a small increase in risk for neoplastic progression with increasing segment length, additional follow-up is needed to determine whether the patterns of risk occurred by chance or represent true differences. Until more data are available, the frequency of endoscopic surveillance should be selected without regard to segment length.