Ischemia/reperfusion and colorectal liver metastases

Abstract

Control of intra-operative bleeding is a primary goal in liver surgery and is traditionally achieved by vascular clamping. The short-term adverse effect of ischemia/reperfusion (I/R) resulting from temporary vascular clamping on hepatocellular function have been well documented. In this thesis we describe for the first time how I/R also affects long-term outcome by accelerating the outgrowth of (residual) colorectal micrometastases. Different aspects of this phenomenon are described: the parameters that predispose for the adverse effects of I/R on tumor growth, the effect of alternative clamping techniques on metastasis outgrowth, the mechanisms that underlie I/R-accelerated tumor growth and pharmacological interventions that interfere with tumor growth after I/R. Finally, the stimulatory effect of thermal ablation, which is associated with pathophysiological events similar to I/R, on the outgrowth of residual tumor cell deposits is described, including interventional strategies to overcome this problem