Bilobar colorectal liver metastases: a new model for preclinical studies

Abstract

This study aimed to develop a new model of colorectal liver metastases (LM) in the rat. Both single macroscopic and multiple bilobar microscopic LM were investigated, as this closely resembled the human situation, before right hepatectomy was performed for 'single' right LM. The single macroscopic LM was elicited by direct injection of DHD/K12 colorectal cancer cells under the capsule of the median liver lobe in immunocompetent BDIX rats. The bilobar micrometastases were elicited by intraportal injection of DHD/K12 cells. A preliminary protocol was conducted to assess the dose of cells required to inject in to the portal vein, using 10(6) , 2×10(6) and 3×10(6) DHD/K12 cells (n=15 rats). The resultant protocol for the experimental model used intraportal injection of 10(6) DHD/K12 cells and direct injections of 0.5×10(6) , 10(6) and 1.5×10(6) DHD/K12 cells (n=15 rats). For both protocols, BDIX rats were sacrificed at day 30 after injection. The preliminary protocol showed that intraportal injection of 10(6) DHD/K12 cells was associated with bilobar micrometastases of 0.8mm mean diameter at day 30. The main protocol assessed that direct injection of 0.5×10(6) under the liver median lobe capsule and intraportal injection of 10(6) DHD/K12 cells were associated at day 30 with a single macroscopic metastasis confined to a liver lobe and bilobar micrometastases, without peritoneal carcinomatosis or lung metastasis. Thus we have developed a new experimental model of bilobar colorectal LM including both macro- and microscopic colorectal LMs, which mimics the human situation and which will be useful in preclinical studies.