To Örebro University

Introduction: Anastomotic leakage following resection surgery for rectal cancer is often linked with reduced overall survival and higher rates of recurrence. Some data suggest that an aggravated inflammatory response as well might lead to worse oncological outcomes, but few attempts have been made to investigate leakage and inflammation in conjunction.

Method: This is a retrospective multicentre cohort study including patients operated with anterior resection for rectal cancer in Sweden during 2014–2018. Anastomotic leakage within 12 months was exposure and primary outcome was recurrence-free survival. Mediation analysis was performed to evaluate the potential effect of systemic inflammatory response, as measured by the highest postoperative C-reactive protein (CRP) level within 14 days of surgery. Confounders were chosen using a causal diagram, while multiple imputation was used to handle missing data.

Result: Some 1036 patients were eligible for analysis, of which 218 (21%) experienced an anastomotic leakage. At the end of follow-up at a median of 1865 days after surgery, recurrence-free survival amounted to 82.6% and 77.8% in the group with and without leakage, respectively. The median maximum postoperative CRP value after surgery was higher in the leakage group (218.5 mg/l), compared with the group without leakage (108 mg/l). Leakage did not confer worse recurrence-free survival (HR 0.66; 95% CI: 0.43–0.94), and there was no apparent effect through postoperative highest CRP (HR 1.12; 95% CI:0.93–1.29).

Discussion: In conclusion, anastomotic leakage, with its accompanying CRP increase, was not found to be associated with recurrence and long-term death after anterior resection for rectal cancer in this patient cohort.