Incidence of esophageal adenocarcinoma in Barrett's esophagus with low-grade dysplasia: a systematic review and meta-analysis

Background: The natural history of low-grade dysplasia (LGD) in patients with Barrett's esophagus (BE) isunclear. Objective: We performed a systematic review and meta-analysis of studies that reported the incidence of esophageal adenocarcinoma (EAC) and/or high-grade dysplasia (HGD) among patients with BE with LGD. Design: Systematic review and meta-analysis of cohort studies. Patients: Patients with BE-LGD, with mean cohort follow-up >= 2 years. Main Outcome Measurements: Pooled incidence rates with 95% confidence intervals (CI) of EAC and/or BE-HGD. Results: We identified 24 studies reporting on 2694 patients with BE-LGD, with 119 cases of EAC. Pooled annual incidence rates of EAC alone and EAC and/or HGD in patients with BE-LGD were 0.54% (95% CI, 0.32-0.76; 24 studies) and 1.73% (95% CI, 0.99-2.47; 17 studies). The results were stable across study setting and location and in high-quality studies. Substantial heterogeneity was observed, which could be explained by stratifying based on LGD/BE ratio as a surrogate for quality of pathology; the pooled annual incidence rates of EAC were 0.76% (95% CI, 0.44-1.09; 14 studies) for LGD/BE ratio <0.15 and 0.32% (95% CI, 0.07-0.58; 10 studies) for LGD/BE ratio > 0.15. The annual rate of mortality not related to esophageal disease in patients with BE-LGD was 4.7% (95% CI, 3.2-6.2; 4 studies). Limitations: Substantial heterogeneity was observed in the overall analysis. Conclusion: The incidence of EAC among patients with BE-LGD is 0.54% annually. The LGD/BE ratio appears to explain the variation observed in the reported incidence of EAC in different cohorts. Conditions not related to esophageal disease are a major cause of mortality in patients with BE-LGD, although additional studies are warranted.