BACKGROUND AND STUDY AIMS: Hybrid argon plasma coagulation (H-APC) is a novel technique for ablation of neoplastic Barrett's esophagus (BE), consisting in submucosal fluid injection and subsequent APC of visible BE. The aim of this study was to assess H-APC efficacy, safety, and tolerability. PATIENTS AND METHODS: We prospectively included patients undergoing H-APC ablation at four Italian Hospitals from September 2022 to March 2024. Patients with BE C3M5 maximum extent, low- or high-grade dysplasia (LGD, HGD) or residual BE after endoscopic resection (ER) of visible lesions were included. Patients who had undergone previous ablative treatments were excluded. The primary endpoints were complete eradication of intestinal metaplasia (CE-IM) and dysplasia (CE-D). Secondary endpoints were safety in terms of major and minor adverse events (AEs) and tolerability, assessed using pain (0-10) and dysphagia (0-5) scores within 7 days post-ablation (NCT05645679). RESULTS: Among the 51 enrolled patients (mean circumferential 0.43 cm
standard deviation [SD] 0.72, mean maximum longitudinal 2.20 cm
SD 1.09) who completed treatment (80 H-APC sessions), 45.1% (23/51) had prior ER of visible lesions. All patients achieved both CE-IM and CE-D (51/51), requiring a mean of 1.51 sessions (SD 0.83). Only one case of fever and absolute dysphagia was observed (1/51
1.96% AEs). Regarding tolerability, mean pain score was 1.3 (SD 1.99) whereas mean dysphagia score was 1.28 (SD 0.56). CONCLUSIONS: The H-APC technique showed promising results in terms of effectiveness and safety with good tolerability in achieving initial CE-IM and CE-D in a selected population of BE patients.