Thermo-responsive aerification and tissue vacuolization for facilitating endoscopic submucosal resection (with video).

Background and Aims Mucosal lifting and its persistence are critical for maintaining the operational space and preventing perforation in endoscopic operation. Although numerous agents have been investigated, optimization is still required for improving their clinical performance. In the present study, we proposed a novel concept of thermoresponsive aerification and tissue vacuolization for submucosal injection. Methods Lifting performance and operational condition were first evaluated in porcine stomachs in vitro and rabbits in vivo. Dodecafluoropentane (DDFP) injection dosage, lifting persistency and operational assistance were quantitatively recorded. Gross and histological pathology were also analyzed to identify DDFP acute toxicity and long-term safety. The endoscopic submucosal dissection (ESD) procedure with DDFP was carried out on pigs in vivo to confirm its operational feasibility, efficacy, and safety. Results Dodecafluoropentane aerification could achieve better mucosal lift with lower dosage (1% of normal saline dosage). Thermoresponsive DDFP aerification could provide continuous replenishment and longer persistence. Meanwhile, its tissue vacuolization effect significantly facilitated submucosal tissue dissection in in vitro study. Similar performance was verified in vivo. The particular vacuole-like submucosal structure was seen after DDFP onset, which also promoted reepithelization and wound healing. No tissue damage, gas embolism, biotoxicity, and physicochemical risk were observed. Conclusion Bioinert DDFP was feasible, efficient, and safe as the novel submucosal lifting candidate.