The liver is the most common site of metastases for colorectal cancer. Complete resection in some patients with resectable liver metastases (LM) can lead to long-term survival and cure. Adjuvant systemic chemotherapy after complete resection of LM improves recurrence-free survival; however, the overall survival benefit is not clear. In selected patients, preoperative systemic treatment for metastatic colorectal cancer can convert unresectable to resectable cancer. This review will focus on patient selection, and integration of perioperative and postoperative systemic treatment to surgery in resectable and initially unresectable LM. Additionally, new drugs and biomarkers will be discussed.

64 Background: Metastasis of cancer cells is associated with numerous activating molecules, including vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and tumor necrosis factor (TNF)-α. Excess VEGF production induces hematogenous metastasis in gastric cancer (GC) cells. To understand the anti-metastatic effect of bevacizumab, an anti-VEGF monoclonal antibody developed for selective inhibition of tumor angiogenesis, we investigated VEGF-induced expression of key adhesion molecules in human umbilical vein endothelial cells (HUVECs) and the inhibitory effect of bevacizumab on the adhesion of GC cells expressing high levels of VEGF. Methods: We measured the soluble VEGF (sVEGF) produced by 7 GC cells by ELISA. We evaluated intercellular adhesion molecule (ICAM)-1, vascular cell adhesion molecule (VCAM)-1, and E-selectin expression in HUVECs pretreated with SNU-1-conditioned medium (SNU-1 CM) or recombinant VEGF (rhVEGF) at different time points by western blotting. Results: We identified that SNU-1 cells secreted the highest sVEGF concentration in 7 GC cells. After rhVEGF pretreatment, ICAM-1 and E-selectin expression were highest at 4–6 h and 2 h, respectively, but VCAM-1 expression was unchanged. Bevacizumab cotreatment markedly decreased VCAM-1 and E-selectin expression to basal levels, whereas ICAM-1 expression was unaffected. The SNU-1 adherent cell percentage decreased following bevacizumab cotreatment of SNU-1 CM- or rhVEGF-pretreated HUVECs. Investigation of SNU-1-cell invasiveness through activated HUVECs revealed less than 10 invasive adherent cells, whereas no cells were found after bevacizumab cotreatment. Conclusions: Our preclinical data suggests that bevacizumab, might contribute to anti-metastasis by inhibiting SNU-1 cell adhesion to HUVECs by reducing E-selectin and VCAM-1 expression.