HPB O03 Preclinical safety and feasibility of <i>in situ</i> Isolated Normothermic Liver Chemoperfusion (INLiC) for enhanced drug delivery

Abstract Background Up to 85% of patients with liver metastases have inoperable disease. Isolated chemoperfusion involves vascular isolation the regional delivery chemotherapy, and aims maximise therapeutic response limit extra-hepatic toxicity. Historically, morbidity associated drug leak from circuit has limited its success. To improve safety this approach, we developed a surgical protocol for Normothermic Liver Chemoperfusion (INLiC) assessed short-term safety, feasibility enhancing delivery. Methods Laparotomy complete, was performed on (n=9) 55–65 Kg pigs. The gastroduodenal artery, portal vein inferior vena cava (IVC) were cannulated normothermic machine perfusion established in situ. Systemic circulation maintained veno-venous bypass. High-dose, intra-arterial doxorubicin delivered isolated liver, circulated 1 hour reconnection performed. Biochemical physiological parameters quantified blood, bile tissue by high performance liquid chromatography. Results A standardised, enable INLiC. Physiological median outflows (1.1 L/min (0.9–1.1)), pH (7.35 (7.26–7.42)), lactate concentration mM (0.33–2.3)) an acceptable peak AST (805 U/L (308–1667)) achieved. Population two-compartmental analysis plasma decay demonstrated distribution half-life 1.3 minutes Cmax 8-times higher than tolerable systemic delivery, due cardiotoxicity. resulting hepatic significantly could be safely achieved (p=0.019). Notably, there no it did not accumulate cardiac or renal tissue. Conclusions INLiC is feasible, safe enables high-dose without accumulation.