Tumour progression and liver regeneration-insights from animal models

Surgery remains the only curative treatment for colorectal liver metastases. For patients with multiple bilobar spread, extended hepatectomy might be required to achieve complete margin-free resection. In such cases, portal vein occlusion has been developed to induce preoperative hypertrophy of the future remnant liver and increase the resectability rate. Evidence now suggests that liver regeneration after hepatectomy and portal vein occlusion has a protumorigenic role, either through an upregulation of growth factors and cytokines or by haemodynamic changes in the blood supply to the liver. Experimental studies have reported a stimulatory effect of liver regeneration on the tumoral volume of liver metastases and on the metastatic potential of cells engrafted in the liver; this effect seems to depend on the timing of hepatectomy and portal vein occlusion. However, the variability of animal tumour models that are used for research in experimental colorectal liver metastases might account for some of the inconsistent and conflicting results. This Review presents clinical and experimental data pertaining to whether liver regeneration causes proliferation of tumour cells. We also analyse the different animal models of colorectal liver metastases in use and discuss current controversies in the field.