Preoperative biomarkers related to inflammation may identify high-risk anastomoses in colorectal cancer surgery: explorative study

Anastomotic leakage is a major complication after colorectal surgery, presumed to correspond with a process of failed wound healing, involving inflammation. Circulating levels of inflammation-related biomarkers were investigated in preoperative samples from 41 patients with leakage, who had elective treatment with a primary anastomosis for non-disseminated colorectal cancer, matched to 41 complication-free controls. A total of 15 inflammation-related proteins were elevated before surgery in patients with rectal cancer with leakage, of which C-X-C motif chemokine 6 and C-C motif chemokine 11 remained significantly increased after controlling for multiplicity. As a corresponding expression pattern difference did not emerge when tissue adjacent to the anastomosis was evaluated with immunohistochemistry, findings may reflect a systemic rather than a local host response. While these findings require validation before implementation into surgical practice, they highlight the need for further translational investigations as a promising research area to help decrease leakage rates. Background Colorectal anastomotic leakage can be considered a process of failed wound healing, for which related biomarkers might be a promising research area to decrease leak rates. Methods Patients who had elective surgery with a primary anastomosis for non-metastatic colorectal cancer, at two university hospitals between 1 January 2010 and 31 December 2015 were included. Patients with an anastomotic leak were identified and matched (1:1) to complication-free controls on the basis of sex, age, tumour stage, tumour location, and operating hospital. Preoperative blood samples were analysed by use of protein panels associated with systemic or enteric inflammation by proteomics, and enzyme-linked immunosorbent assays. Multivariable projection methods were used in the statistical analyses and adjusted for multiple comparisons to reduce false positivity. Rectal cancer tissue samples were evaluated with immunohistochemistry to determine local expression of biomarkers that differed significantly between cases and controls. Results Out of 726 patients undergoing resection, 41 patients with anastomotic leakage were matched to 41 controls. Patients with rectal cancer with leakage displayed significantly elevated serum levels of 15 proteins related to inflammation. After controlling for a false discovery rate, levels of C-X-C motif chemokine 6 (CXCL6) and C-C motif chemokine 11 (CCL11) remained significant. In patients with colonic cancer with leakage, levels of high-sensitivity C-reactive protein (hs-CRP) were increased before surgery. Local expression of CXCL6 and CCL11, and their receptors, were similar in rectal tissues between cases and controls. Conclusion Patients with anastomotic leakage could have an upregulated inflammatory response before surgery, as expressed by elevated serological levels of CXCL6 and CCL11 for rectal cancer and hs-CRP levels in patients with colonic cancer respectively. Preoperative inflammation-related serum proteins were evaluated in a case-control study of 41 patients with anastomotic leakage matched 1:1 with 41 complication-free controls. The chemokines C-X-C motif chemokine 6 and C-C motif chemokine 11 were significantly increased before surgery in patients with rectal cancer and leakage, a finding requiring further validation.