EUS-guided portal injection chemotherapy for treatment of hepatic metastases: feasibility in the acute porcine model

Abstract

Direct injection of chemotherapy into the portal vein for treatment of liver metastases may increase hepatic tissue levels while decreasing systemic levels and toxicities. We aimed to evaluate EUS-guided portal injection chemotherapy (EPIC) by using drug-eluting microbeads or nanoparticles and compare it with systemic injection. We conducted a comparative feasibility trial in the acute porcine model (24 anesthetized pigs). Pigs were treated with irinotecan, doxorubicin, or albumin-bound paclitaxel nanoparticles (n = 8/group). Within each group, pigs were treated with EPIC or a systemic intravenous injection of drug and saline solution into the portal vein (n = 4/treatment). Irinotecan or doxorubicin were loaded onto microbeads for EPIC treatment only. We examined drug levels in tissue (1 hour) and plasma (15 minutes). EUS-guided access and injection was successful in all animals. EPIC with irinotecan-loaded microbeads showed nearly double the hepatic concentration compared with systemic injection (6242 vs 3692 ng/g) and almost half the systemic levels. EPIC with doxorubicin-loaded microbeads showed a 5-fold increase in hepatic levels (35,450 vs 6930 ng/g) and a 30-fold decrease in cardiac levels (153 vs 4805 ng/g) compared with systemic administration (P < .05 for both). EPIC with albumin-bound paclitaxel nanoparticles increased hepatic concentrations by 60% and decreased systemic levels by 24% to 32%. EPIC holds promise as a new treatment for hepatic metastases.