EP.TH.494Preclinical feasibility of in situ isolated normothermic liver chemoperfusion

Abstract Aims Up to 85% of patients with liver metastases have inoperable hepatic tumour burden. Isolated perfusion involves vascular isolation the in situ and regional delivery chemotherapy, avoiding dose-limiting extra-hepatic toxicity. In this series, we develop a surgical protocol demonstrate feasibility isolated normothermic (INLP) investigate short-term safety delivering high-dose chemotherapy. Methods Laparotomy complete, was performed on 55-65Kg pigs (n = 6). The artery (HA), portal vein (PV) inferior vena cava were cannulated NMP established. Veno-venous bypass maintained systemic circulation. High-dose doxorubicin administered liver, circulated for 1 hour reconnection performed. Physiological parameters measured quantified blood, bile tissue by high-performance liquid chromatography. Results INLP achieved physiological flow rates (PV 0.7L/min (0.6-0.9L/min); HA 0.3L/min (0.2-0.4L/min)) pH (median 7.3 (7.24-7.38)), median lactate 0.42mmol/L. Median peak AST ALT 1045 U/L 47 respectively. Doxorubicin decay fitted 2-compartmental model; distribution half-life 1.9 minutes plasma Cmax higher than if given systemically resulting mean levels 26+/-11.6 µg/g. There no leak during undetectable kidney or heart. Conclusions Surgical situ, concurrent veno-venous is feasible enables drug therapeutic off-target Further studies are required.