title: Perfusion to colorectal cancer liver metastases is not uniform and depends on tumor location and feeding vessel.
abstract: Future effective therapies for hepatic metastases may depend on a better understanding of perfusion to these tumors. The purpose of this project was to define blood flow to colorectal cancer liver metastases using quantitative autoradiography (QAR). Liver tumors were established in F1 hybrids of WF x BN rats by intrasplenic injection of a DMH-induced rat colon adenocarcinoma. Rats underwent laparotomy 4-5 weeks later and [14C]iodoantipyrine (a radiotracer) was infused via the hepatic artery (HA) or portal vein (PV). Livers were harvested, frozen in liquid nitrogen, and sectioned at 20 microns through all tumors. QAR compared optical density of cross sections of tumors to surrounding normal liver tissue. Tumor:liver perfusion ratios (T/L PR) and tumor center:tumor periphery perfusion ratios (C/P PR) were calculated. All groups were analyzed with regard to tumor location and size. Seventy-seven tumors in 6 rats in the HA infusion group were analyzed; 74 tumors in 8 rats in the PV group were analyzed. Statistical analysis was by repeated measures analysis of variance. Mean HA T/L PR = 0.97 +/- 0.13, mean PV T/L PR = 0.25 +/- 0.11. Mean HA T/L PR for deep tumors was 1.38 +/- 0.17 and for superficial tumors was 0.57 +/- 0.15 (P < 0.01). Mean HA T/L PR for small tumors was 1.09 +/- 0.12 and for large tumors was 0.86 +/- 0.21 (P = 0.27). Mean PV T/L PR for deep tumors was 0.27 +/- 0.14 and for superficial tumors was 0.24 +/- 0.15 (P = 0.71). Mean PV T/L PR for small tumors was 0.31 +/- 0.15 and for large tumors was 0.20 +/- 0.14 (P = 0.54). Mean HA C/P PR = 1.15 +/- 0.15, mean PV C/P PR = 0.81 +/- 0.14 (P = 0.06). Mean HA C/P PR for small tumors was 1.37 +/- 0.16 and for large tumors was 0.92 +/- 0.17 (P = 0.01). Mean PV C/P PR for small tumors was 0.78 +/- 0.18 and for large tumors was 0.72 +/- 0.13 (P = 0.71). HA perfusion of tumors is significantly higher than PV perfusion compared to surrounding normal liver tissue. HA perfusion varies significantly depending on tumor location. There was a trend toward HA perfusion to the tumor center being slightly greater than to the periphery whereas the reverse was seen for PV perfusion. Tumor size did not affect overall perfusion but it did affect regional HA tumor perfusion.
authors.affiliation: Department of Colorectal Surgery, Cleveland Clinic Foundation, Ohio 44195, USA.
authors.forename: S
authors.initials: S
authors.lastname: Casillas
authors.forename: D W
authors.initials: DW
authors.lastname: Dietz
authors.forename: M I
authors.initials: MI
authors.lastname: Brand
authors.forename: S C
authors.initials: SC
authors.lastname: Jones
authors.forename: A
authors.initials: A
authors.lastname: Vladisavljevic
authors.forename: J W
authors.initials: JW
authors.lastname: Milsom
mesh_terms: D000230:Adenocarcinoma / Q000098:blood supply* / Q000000981:diagnostic imaging / Q000556:secondary*; D000818:Animals; D000983:Antipyrine / Q000008:administration & dosage / Q000031:analogs & derivatives; D001345:Autoradiography / Q000379:methods; D015179:Colorectal Neoplasms; D005260:Female; D006499:Hepatic Artery; D007261:Infusions, Intra-Arterial; D007262:Infusions, Intravenous; D007457:Iodine Radioisotopes / Q000008:administration & dosage; D008114:Liver Neoplasms, Experimental / Q000098:blood supply* / Q000000981:diagnostic imaging / Q000556:secondary*; D008297:Male; D011169:Portal Vein; D011877:Radionuclide Imaging; D051381:Rats; D011914:Rats, Inbred BN; D011920:Rats, Inbred WF; D012039:Regional Blood Flow
chemical_list: D007457:Iodine Radioisotopes; D000983:Antipyrine; C008135:iodoantipyrine