Chemotherapy-associated hepatotoxicity and surgery for colorectal liver metastases

Abstract

Background: Preoperative systemic chemotherapy is increasingly used in patients who undergo hepatic resection for colorectal liver metastases (CLM). Although chemotherapy-related hepatic injury has been reported, the incidence and the effect of such injury on patient outcome remain ill defined.Methods: A systematic review of relevant studies published before May 2006 was performed. Studies that reported on liver injury associated with preoperative chemotherapy for CLM were identified and data on chemotherapy-specific liver injury and patient outcome following hepatic resection were synthesized and tabulated.Results: Hepatic steatosis, a mild manifestation of non-alcoholic fatty liver disease (NAFLD), may occur after treatment with 5-fluorouracil and is associated with increased postoperative morbidity. Nonalcoholic steatohepatitis, a serious complication of NAFLD that includes inflammation and hepatocyte damage, can occur after treatment with irinotecan, especially in obese patients. Irinotecan-associated steatohepatitis can affect hepatic reserve and increase morbidity and mortality after hepatectomy. Hepatic sinusoidal obstruction syndrome can occur in patients treated with oxaliplatin, but does not appear to be associated with an increased risk of perioperative death. Conclusion:Preoperative chemotherapy for CLM induces regimen-specific hepatic changes that can affect patient outcome. Both response rate and toxicity should be considered when selecting preoperative chemotherapy in patients with CLM.

The Oncosurgery Approach to Managing Liver Metastases from Colorectal Cancer: A Multidisciplinary International Consensus

“…Complete resection is possible if liver vascularity can be preserved, the FLR is adequate with reference to body weight and total liver volume, and the quality of the remnant liver parenchyma is acceptable [17]. MRI and high-quality CT can be used for preoperative imaging; the choice of modality is dependent on the precise point in the clinical pathway and local expertise.…”

“…A range of strategies has now been developed to render a patient's disease surgically resectable (e.g., portal vein embolization, neoadjuvant chemotherapy, hepatectomy combined with radiofrequency ablation, two-stage hepatectomy) [82,83]. Portal vein embolization is indicated when the FLR as a proportion of total liver volume is 20%-30% in patients with a normal liver and Յ40% in patients who have had extensive chemotherapy [17,84]. The efficacy of conversion chemotherapy has increased dramatically in recent years, and it has become the best means of downsizing tumoral disease and converting patients with unresectable disease to resectability [30].…”

Targeted molecular therapies (cetuximab and bevacizumab) do not induce additional hepatotoxicity: Preliminary results of a case–control study

“…However, the number of patients receiving adjuvant chemotherapy for the primary tumour was similar between the different groups avoiding this bias. There was also no correlation between the cumulative dose of oxaliplatin and the presence or severity of SOS (29). The effect of the delay between the last dose of chemotherapy and the liver surgery on postoperative morbidity and mortality was analysed by Welsh et al (30).…”

Designing Liver Resections and Pushing the Envelope with Resections for Hepatic Colorectal Metastases

“…The volume of liver parenchyma that will remain after resection, i.e., the future liver remnant (FLR), is of paramount importance in hepatic resections [11][12][13]. Conventionally 20 % of the total liver volume has been regarded as the minimum safe FLR in a patient with normal hepatic function [7]; however, an FLR of 30-40 % is necessary if the patient has received cytotoxic chemotherapy, since chemotherapeutic agents used to treat CRC cause hepatic injury, such as steatosis and sinusoidal obstruction with oxaliplatin and steatohepatitis with irinotecan [12,14].…”