Effect of major liver resection on colon cancer metastasis in the lung and liver.

Abstract

e14014 Background: Liver resection is a common procedure in liver-metastatic colon cancer. However, recurrence is common and distant liver metastasis may be appear after liver resection. Methods: Experimental liver metastases were established by spleen injection of the Colon 26 murine colon cancer cell line expressing green fluorescent protein (GFP) into transgenic nude mice expressing red fluorescent protein (RFP). Experimental liver metastases was established by splenic injection of Colon-26-GFP. Experimental lung metastases were established by tail vein injection with Colon 26-GFP. Three days after cell injection into the spleen or tail vein, groups of mice underwent liver resection (35%+35% [repeated minor resection] vs. 70% [major resection]). Metastatic tumor growth was measured by color-coded fluorescence imaging of the GFP-expressing cancer cells and RFP-expressing stroma. Results: Although major and repeated minor resection removed the same volume of liver parenchyma, the two procedures had very different effects on metastatic tumor growth. Major resection, stimulated liver and lung metastatic growth as well as recruitment of host-derived stroma into the metastases compared to repeated minor resection. Repeated minor resection did not stimulate metastasis or stromal recruitment. There was no significant difference in liver regeneration between the two groups. TGF-β was also preferentially stimulated by major resection. Conclusions: Host-derived stroma density, which is stimulated by major resection compared to repeated minor resection, may stimulate metastatic growth. Stromal growth may be stimulated by TGF-β. The results of this study indicate that caution should be taken when planning a major liver resection for metastatic colorectal cancer. Conservative resections that spare liver parenchyma should be considered whenever possible.