Development of Esophageal Adenocarcinoma in Patients with Barrett's Esophagus and High Grade Dysplasia Undergoing Survilence: A Meta-Analysis and Systematic Review

Abstract

Purpose: Histologically, patients with Barretts Esophagus (BE) are stratified as those with no dysplasia, low grade dysplasia (including indeterminate for dysplasia), and high grade dysplasia (HGD). HGD patients are at the highest risk for development of esophageal cancer. The reported rate of cancer development in HGD patients undergoing surveillance is varied, making management of these patients very controversial i.e. surgery vs. endoscopic therapy vs. observation. Our aim was to determine the exact cancer incidence in patients with HGD undergoing surveillance endoscopy. Method: We searched for articles in Medline, Pubmed, Ovid journals, Cumulative index to nursing & Allied health literature, International pharmaceutical abstracts, old Medline, Medline non-indexed citations, and Cochrane control trial registry. Articles which met the following inclusion criteria were selected: patients with histologically proven BE and HGD, patients not having undergone endoscopic ablation or surgical therapy, no esophageal cancer at the time of enrollment or within 6 months, and follow up reported in person-time. All studies with a mean or median follow-up duration of less than six months were excluded. Weighted mean event rate for a study population was utilized to obtain a summary standardized rate, which was expressed as the direct standardized incidence rate (DSR). Approximate confidence intervals for DSR were calculated by both binomial model and Chiang's normal approximation to Poisson rate sums. A test of heterogeneity was performed using the Mantel-Haenszel's method. Results: Data from four articles which met the inclusion criteria were analyzed. This included 236 patients with HGD who were followed for 1240.5 patient years. A total of 69 esophageal cancers occurred in this group, giving a crude incidence rate of 5.57 per 100 patient-years. The direct standardized cancer incidence rate was 6.58 per 100 patient-years (95% confidence interval = 4.97 to 8.19). The p value for the test of heterogeneity was 0.02. Conclusions: In BE patients with HGD undergoing surveillance, the standardized incidence rate of esophageal cancer development is 6.5 per 100 patient years and is higher than the crude rate. These data will help better inform physicians and patients in management decisions and also help compare the extent of any reduction in cancer incidence after intervention therapy for HGD.