Safe liver resection following chemotherapy for colorectal metastases is a matter of timing

Abstract

Neoadjuvant chemotherapy (NC) can improve the resectability of hepatic colorectal metastases (CRM). However, there is concern regarding its impact on operative risk. We reviewed 750 consecutive liver resections performed for CRM in a single unit (1996 -2005) to evaluate whether NC affected morbidity and mortality. Redo hepatic resections or patients receiving adjuvant chemotherapy following primary resection were excluded. A total of 245 resections were performed in patients not requiring NC (control group) (mean age 63, 67% male) and 252 in patients who had NC (mean age 62, 67% male). The mean (s.d.) duration of surgery was less in the control group (241(64) vs 255(64)min, P ¼ 0.014) as was the mean blood loss (390(264) vs 449(424)ml, P ¼ 0.069). Postoperative mortality (2 vs 2%) and morbidity (27 vs 29%, P ¼ 0.34) was similar between groups. More NC patients developed septic (2.4%) or respiratory (10.3%) complications compared to controls (0 and 5.3%, Po0.03), with significantly more surgical complications if the interval between stopping NC and undergoing surgery was p4 weeks (11%), compared to 5 -8 (5.5%) or 9 -12 (2.6%) weeks (P ¼ 0.009). The data suggest that liver resection for CRM is safe following NC. Early hepatobiliary involvement in multidisciplinary cancer care may lead to avoidance of potential perioperative adverse events.

Surgery with curative-intent in patients treated with first-line chemotherapy plus bevacizumab for metastatic colorectal cancer First BEAT and the randomised phase-III NO16966 trial

“…Reversible peri-operative complications were more frequent in the chemotherapy arm (25% vs 16%, P ¼ 0.04) with notable increases in biliary fistulae, hepatic failure and intra-abdominal infections, but no difference in bleeding, venous thromboembolism or postoperative death rates. Whether the increase in complications related to the timing of surgery relative to chemotherapy, or simply the exposure to chemotherapy itself, cannot be determined from these data, although data from a retrospective series of 750 patients undergoing hepatic resection, suggest that the rate of complications is highest in patients undergoing surgery within 4 weeks of chemotherapy (Welsh et al, 2007).…”

Defining patient outcomes in stage IV colorectal cancer: a prospective study with baseline stratification according to disease resectability status

“…An additional noteworthy finding in this study was an increase in the post-operative complication rate in patients who received peri-operative chemotherapy at 25 vs 16% in the surgery-alone arm (Nordlinger et al, 2008). Data suggest that the choice of chemotherapeutic agents , length of pre-operative therapy (Aloia et al, 2006;Karoui et al, 2006) and interval between chemotherapy and surgery (Welsh et al, 2007) may all influence the associated surgical morbidity. The relatively short interval between chemotherapy and surgery in the EORTC study (median 4.1 weeks) may have contributed to the excess surgical complication rate seen.…”

Neoadjuvant Chemotherapy for Colorectal Liver Metastases

“…This has led to a general recommendation to limit the degree of exposure to chemotherapy in the preoperative phase to a period of two to three months, if possible. In addition, lower morbidity rates have been reported when liver resection is performed more than 4 weeks after stopping chemotherapy (Welsh et al, 2007). There is evidence that some of the biological agents modify the degree of hepatic injury induced by cytotoxic agents.…”