PURPOSE: To evaluate whether intrahepatic flow alterations occur during formation of hepatic colorectal cancer metastases and to identify possible causes of these alterations.
MATERIALS AND METHODS: Intravital imaging of exteriorized livers was performed in 72 live mice. Three groups of mice were studied: a sham-operated control group (n = 24), a group with nonmetastasizing subcutaneous gliomas (n - 24), and a group with developing hepatic CX-1 colon cancer metastases (n = 24). Micro-vascular flow parameters, leukocyte-endothelial interactions, and wall shear stress were directly measured in hepatic sinusoids and postsinusoidal venules at 2-day intervals prior to and during the development of metastases. The Kruskal-Wallis test was used initially to test for overall equality of medians in each data group. Single posttest comparisons of independent samples were performed with the Mann-Whitney test, with an overall statistical significance of .05.
RESULTS: Prior to the development of visible colorectal cancer metastases, significant (P < .05) reductions occurred in sinusoidal and postsinusoidal flow and wall shear rates, coupled with increased leukocyte rolling and adherence. With tumor growth, flow was further compromised in 92% of tumors larger than 0.5 mm in diameter by extrinsic compression of sinusoids and portal venules and narrowing caused by adherent leukocytes.
CONCLUSION: Significant intrahepatic flow alterations occur in mouse livers prior to growth of visible metastases and provide a rational explanation for elevation in the Doppler perfusion index that occurs prior to tumor formation.