Barrett's Esophagus and Adenocarcinoma Risk

Abstract

In Brief Objective: To establish the incidence and risk factors for progression to high-grade intraepithelial neoplasia (HG-IEN) or Barrett's esophageal adenocarcinoma (BAc) in a prospective cohort of patients with esophageal intestinal metaplasia [(BE)]. Background: BE is associated with an increased risk of BAc unless cases are detected early by surveillance. No consistent data are available on the prevalence of BE-related cancer, the ideal surveillance schedule, or the risk factors for cancer. Methods: In 2003, a regional registry of BE patients was created in north-east Italy, establishing the related diagnostic criteria (endoscopic landmarks, biopsy protocol, histological classification) and timing of follow-up (tailored to histology) and recording patient outcomes. Thirteen centers were involved and audited yearly. The probability of progression to HG-IEN/BAc was calculated using the Kaplan-Meier method; the Cox regression model was used to calculate the risk of progression. Results: HG-IEN (10 cases) and EAc (7 cases) detected at the index endoscopy or in the first year of follow-up were considered to be cases of preexisting disease and excluded; 841 patients with at least 2 endoscopies {median, 3 [interquartile range (IQR): 2–4); median follow-up = 44.6 [IQR: 24.7–60.5] months; total 3083 patient-years} formed the study group [male/female = 646/195; median age, 60 (IQR: 51–68) years]. Twenty-two patients progressed to HG-IEN or BAc (incidence: 0.72 per 100 patient-years) after a median of 40.2 (26.9–50.4) months. At multivariate analysis, endoscopic abnormalities, that is, ulceration or nodularity (P = 0.0002; relative risk [RR] = 7.6; 95% confidence interval, 2.63–21.9), LG-IEN (P = 0.02, RR = 3.7; 95% confidence interval, 1.22–11.43), and BE length (P = 0.01; RR = 1.16; 95% confidence interval, 1.03–1.30) were associated with BE progression. Among the LG-IEN patients, the incidence of HG-IEN/EAc was 3.17 patient-years, that is, 6 times higher than in BE patients without LG-IEN. Conclusions: These results suggest that in the absence of intraepithelial neoplastic changes, BE carries a low risk of progression to HG-IEN/BAc, and strict surveillance (or ablative therapy) is advisable in cases with endoscopic abnormalities, LG-IEN or long BE segments. The incidence of high-grade noninvasive neoplasia and adenocarcinoma and the risk factors for progression were established in a prospective cohort of 841 patients with Barrett's esophagus on the basis of regular endoscopic follow-up for a total of 3083 patient-years. The overall incidence of high-grade intraepithelial neoplasia/adenocarcinoma was 7.2 per 1000 patient-years. The presence of endoscopic abnormalities (ulceration or nodularity), low-grade noninvasive neoplasia at histology, and the length of the segment of Barrett's esophagus were independently associated with progression.