BACKGROUND AND STUDY AIMS:Endoscopic submucosal dissection (ESD) of early gastrointestinal tumors has been shown to achieve complete resection rates superior to endoscopic mucosal resection (EMR), but at the cost of higher risk. The aim of this study was to prospectively assess the feasibility and oncological results of ESD in patients with neoplastic Barrett's esophagus in conjunction with subsequent radiofrequency ablation (RFA). METHODS:Patients with Barrett's esophagus who had visible lesions containing high grade intraepithelial neoplasia (HGIN) or mucosal adenocarcinoma (MAC) up to 3 cm in diameter were included in the study. ESD was performed using a new waterjet-assisted system (WESD) with a HybridKnife (Erbe Elektromedizin GmbH, Tübingen, Germany). Primary outcome was the rate of complete tumor resection. RFA of residual intestinal metaplasia was offered to all patients with at least two negative follow-up endoscopies. RESULTS:Of 30 patients (m:f = 21:9; median age 60 years) with biopsy-proven MAC (n = 24) or HGIN (n = 6) with a median diameter of 2 cm, complete resection of the targeted area was achieved in 29 patients (96.7 %; 95 % confidence interval [CI] 82 % - 99 %); en bloc resection was achieved in 27 of these patients (90.0 %; 95 %CI 74 % - 97 %). Minor delayed bleedings occurred in two patients. One patient died due to a sudden cardiac death 7 days after an uneventful WESD. Specimen histology (n = 29) revealed no neoplasia in 3 patients, HGIN in 2, MAC in 21, and submucosal cancer in 3; complete resection was histologically confirmed in only 10 of the 26 patients with HGIN or adenocarcinoma (38.5 %; 95 %CI 22 % - 57 %). However, endoscopic follow-up (median 17 months) showed complete remission of neoplasia in 27 /28 (96.4 %; 95 %CI 81 % - 99 %) patients who underwent successful WESD and were alive at 30 days. One patient underwent EMR of residual tumor. All Barrett's tissue was eradicated by ESD alone in 15 cases and by additional RFA in 8 /10 cases (not done in three patients). CONCLUSIONS:ESD of Barrett's neoplasia is feasible and safe, but does not achieve sufficient R0 resection rates to warrant its recommended use over piecemeal EMR. In combination with RFA it can achieve complete eradication of neoplastic and non-neoplastic Barrett's epithelium. The discrepancy between insufficient oncological resection and good medium-term results needs to be studied further.