Retrograde-outflow percutaneous isolated hepatic perfusion using cisplatin: A pilot study on pharmacokinetics and feasibility

Objectives This study aimed to evaluate the feasibility and underlying pharmacokinetics of the retrograde-outflow technique for percutaneous isolated hepatic perfusion (PIHP). Methods Retrograde-outflow PIHP was performed in 12 male pigs (weight, 37–44 kg) by redirecting hepatic outflow through the portal vein. Blood with cisplatin (2.5 mg/kg) in an extracorporeal circuit was circulated through the liver under isolation using rotary pumps with balloon catheters. Hepatic angiographic examinations were conducted during perfusion, and histopathological examinations of the organs were conducted after perfusion. The maximum platinum concentration ( C max ), area under the concentration-time curve (AUC), and chronologic laboratory data were measured. Results Retrograde-outflow isolated hepatic angiography confirmed that contrast media flowed into the portal veins in all 12 pigs. The hepatic veins and inferior vena cava were not opacified. Hepatic C max (86.3 mg/l) was 39-fold greater than systemic C max (2.2 mg/l), and hepatic AUC (1330.8 min · mg/l) was 30-fold greater than systemic AUC (44.6 min · mg/l). Histopathological examinations revealed no ischaemic changes or other abnormalities in the liver, duodenum, small intestine, or colon. Within 1 week of the procedure, chronologic laboratory data (n = 3) normalized or returned to pre-therapy levels. Conclusions The retrograde-outflow technique appears to enable safe and feasible PIHP therapy. Key Points • The portal vein acted as an outflow tract under retrograde-outflow PIHP. • Plasma hepatic-to-systemic exposure ratio was 39.2 for the maximum platinum concentration. • Plasma hepatic-to-systemic exposure ratio was 29.8 for the AUC. • The retrograde-outflow technique appears to enable safe and feasible PIHP.