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

Abstract

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-1 α (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.