title: EUS-guided portal injection chemotherapy for treatment of hepatic metastases: feasibility in the acute porcine model.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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).
  
  
  RESULTS
  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%.
  
  
  CONCLUSIONS
  EPIC holds promise as a new treatment for hepatic metastases.
authors.affiliation: Division of Gastroenterology and Hepatology, Mayo Clinic, Scottsdale, Arizona, USA.
authors.forename: Douglas O
authors.initials: DO
authors.lastname: Faigel
authors.affiliation: School of Life Sciences, Arizona State University, Tempe, Arizona, USA.
authors.forename: Douglas F
authors.initials: DF
authors.lastname: Lake
authors.affiliation: Center for Procedural Innovation, Mayo Clinic, Scottsdale, Arizona, USA.
authors.forename: Tracy L
authors.initials: TL
authors.lastname: Landreth
authors.affiliation: Center for Procedural Innovation, Mayo Clinic, Scottsdale, Arizona, USA.
authors.forename: Catherine C
authors.initials: CC
authors.lastname: Kelman
authors.affiliation: Research Laboratories, Mayo Clinic, Scottsdale, Arizona, USA.
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Marler
mesh_terms: D000208:Acute Disease; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D019160:Endosonography / Q000379:methods*; D005240:Feasibility Studies; D007275:Injections, Intravenous; D008113:Liver Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000556:secondary; D008297:Male; D008863:Microspheres; D009374:Neoplasms, Experimental; D011169:Portal Vein; D013552:Swine
chemical_list: D000970:Antineoplastic Agents