title: The effect of portal venous flow on the washout of a regionally injected marker substance 99mTc-methylene diphosphonate after hepatic arterial blockade with degradable starch microspheres.
abstract: Patients with hepatic metastases derived from colorectal carcinoma have a poor prognosis. Regional chemotherapy, either alone, or combined with agents such as degradable starch microspheres (DSM) that reduce or abolish intrahepatic arterial flow and potentiate the delivery of cytotoxics to hepatic metastases, have not significantly improved survival. We have investigated one positive mechanism, namely the effect of portal venous washout of cytotoxics, for the poor efficacy of drugs administered either alone or in combination with DSM via the hepatic artery in the rat. Using a radiolabelled marker, 99mTc-methylene diphosphonate (MDP), to represent a cytotoxic drug, the initial studies indicated that with the hepatic artery and portal vein clamped, a volume of 0.05 ml of the marker administered via the hepatic artery resulted in the most uniform intrahepatic distribution with minimal washout into the systemic circulation (21 +/- 3.7%). When the hepatic artery was clamped, the washout of MDP was reduced from 100% (with clamps on the portal vein and hepatic artery) to 84.2 +/- 7.7%. DSM administered concomitantly with MDP, resulted in a greater reduction of the portal venous washout of the marker (63 +/- 2.4%). Administration of DSM and MDP via the hepatic artery and with the portal vein clamped further reduced the washout of the marker to (21 +/- 2.26), results similar to those observed with inflow vessel clamps. Following restoration of portal venous flow, there was a rapid washout of 53.7 +/- 7.6% of the marker into the systemic circulation. The results of this study suggest that portal venous washout of regionally delivered cytotoxics, either alone or in combination with DSM, offer an explanation for the poor efficacy of regional chemotherapy in improving the prognosis of patients with hepatic metastases.
authors.affiliation: University Department of Surgery, Royal Liverpool Hospital, UK.
authors.forename: D M
authors.initials: DM
authors.lastname: Nott
authors.forename: J
authors.initials: J
authors.lastname: Yates
authors.forename: S J
authors.initials: SJ
authors.lastname: Grime
authors.forename: M
authors.initials: M
authors.lastname: Maltby
authors.forename: T G
authors.initials: TG
authors.lastname: Cooke
authors.forename: S A
authors.initials: SA
authors.lastname: Jenkins
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage; D001783:Blood Flow Velocity; D016461:Chemoembolization, Therapeutic; D006499:Hepatic Artery; D008102:Liver Circulation / Q000502:physiology; D008297:Male; D008863:Microspheres; D011169:Portal Vein / Q000502:physiology*; D051381:Rats; D011916:Rats, Inbred F344; D013213:Starch; D013669:Technetium Tc 99m Medronate
chemical_list: D000970:Antineoplastic Agents; D013213:Starch; D013669:Technetium Tc 99m Medronate