Chemotherapy prior to hepatic resection for colorectal liver metastases: Helpful until harmful?

Background: Improved efficacy of chemotherapy for treatment of colorectal liver metastases (CLM) has renewed interest in the use of systemic treatment as part of a 'potentially curative' treatment plan for patients with CLM. Controversy exists regarding potential hepatotoxicity of therapy delivered before liver resection. Methods: Medline reports of pathologic changes in liver and tumor, specific chemotherapy types and clinical outcomes were examined. Results: Hepatic steatosis without inflammation (simple steatosis) may occur with chemotherapy treatment, but hepatic resection can be performed safely even in patients with severe (>30%) steatosis. Steatohepatitis is associated with irinotecan therapy and an increased risk for liver failure and death after hepatic resection. Hepatic sinusoidal obstruction can occur with oxaliplatin treatment and appears to increase in severity with prolonged treatment (>6 cycles). Bevacizumab can be used safely when discontinued >5 weeks before liver resection. Importantly, bevacizumab decreases the incidence and severity of sinusoidal injury with oxaliplatin therapy. Pathologic response is improved with the addition of bevacizumab and is evolving as an independent predictor of long-term survival. Conclusions: Chemotherapy-related liver injuries are regimen-specific. Targeted therapy combined with cytotoxic therapy is safe and most effective. With the use of limited chemotherapy combining appropriately selected agents, the risk of surgical complications can be minimized and the overall effect and benefits of treatment optimized.