Accurate prediction of anastomotic leakage after colorectal surgery using plasma markers for intestinal damage and inflammation

BACKGROUND: Anastomotic leakage is a frequent and life-threatening complication after colorectal surgery. Early recognition of anastomotic leakage is critical to reduce mortality. Because early clinical and radiologic signs of anastomotic leakage are often nonspecific, there is an urgent need for accurate biomarkers. Markers of inflammation and gut damage might be suitable, as these are hallmarks of anastomotic leakage. STUDY DESIGN: In 84 patients undergoing scheduled colorectal surgery with primary anastomosis, plasma samples were collected preoperatively and daily after surgery. Inflammatory markers, C-reactive protein; calprotectin; and interleukin-6, and intestinal damage markers, intestinal fatty acid binding protein; liver fatty acid binding protein; and ileal bile acid binding protein, were measured. Diagnostic accuracy of single markers or combinations of markers was analyzed by receiver operating characteristic curve analysis. RESULTS: Anastomotic leakage developed in 8 patients, clinically diagnosed at median day 6. Calprotectin had best diagnostic accuracy to detect anastomotic leakage postoperatively. Highest diagnostic accuracy was obtained when C-reactive protein and calprotectin were combined at postoperative day 3, yielding sensitivity of 100%, specificity of 89%, positive likelihood ratio = 9.09 (95% CI, 4.34-16), and negative likelihood ratio = 0.00 (95% CI, 0.00-0.89) (p < 0.001). Interestingly, preoperative intestinal fatty acid binding protein levels predicted anastomotic leakage at a cutoff level of 882 pg/mL with sensitivity of 50%, specificity of 100%, positive likelihood ratio = infinite (95% CI, 4.01-infinite), and negative likelihood ratio = 0.50 (95% CI, 0.26-0.98) (p < 0.0001). CONCLUSIONS: Preoperative intestinal fatty acid binding protein measurement can be used for anastomotic leakage risk assessment. In addition, the combination of C-reactive protein and calprotectin has high diagnostic accuracy. Implementation of these markers in daily practice deserves additional investigation