Serum cytokines in early prediction of anastomotic leakage following low anterior resection

Introduction
Anastomotic leakage continues to be one of the most serious complications following low anterior resections. Early diagnosis of a leak is difficult but critical to minimize morbidity and mortality.

Aim
To evaluate changes in serum concentrations of 27 different cytokines following low anterior resection, with the goal of finding new, early biomarkers of anastomotic leak.

Material and methods
This is a prospective observational study that includes 32 patients undergoing elective low anterior resection for rectal cancer. Blood samples were collected preoperatively and on postoperative day 3.

Results
Five patients developed anastomotic leak (15%). On postoperative day 3, high-sensitivity C-reactive protein (hs-CRP), interleukin (IL)-6, and regulated on activation, normal T cell expressed and secreted (RANTES) were significantly higher in patients with anastomotic leak, while IL-9 and fibroblast growth factor (FGF) 2 were significantly lower. Analysis of relative changes in the concentration of cytokines from preoperative to postoperative day 3 revealed a significant increase of IL-6 and granulocyte-colony stimulating factor (G-CSF) in patients with an anastomotic leak. Upon receiver operating curve (ROC) analysis, the performance of hs-CRP was found to be excellent (AUC = 0.99), and performance of ΔIL-6, IL-6, RANTES, and FGF2 was good (AUC: 0.81–0.87). Patients who developed an anastomotic leak preoperatively had significantly lower levels of macrophage inflammatory protein-1α (MIP-1α), monocyte chemotactic protein-1 (MCP-1), IL-8, FGF2, and G-CSF.

Conclusions
The single most accurate serum biomarker of anastomotic leakage continues to be hs-CRP. However, when analyzing relative changes of cytokine levels, ΔIL-6 appears to be a better leak predictor than CRP.