Plasma markers for anastomotic leakage after colorectal surgery
Kostan W. Reisinger1, Joep P.M. Derikx1, Karel W.E. Hulsewé2, Annemarie A. van
Bijnen1, Maarten F. von Meyenfeldt1, Martijn Poeze1
1. Department of Surgery, Maastricht University Medical Center & Nutrim School for
Nutrition, Toxicology and Metabolism, Maastricht University, Maastricht, the
Netherlands.
2. Department of Surgery, Orbis Medical Center, Sittard, the Netherlands
Background
Anastomotic leakage is a frequent complication after colorectal surgery (incidence
8% in the Netherlands), associated with high short-term mortality rates of up to 40%.
Moreover, anastomotic leakage negatively impacts cancer specific survival rates.
Early re-intervention is critical to reduce mortality. As early clinical and radiological of
anastomotic leakage are often non-specific, there is an urgent need for accurate
biomarkers. Markers of inflammation and gut damage may be suitable, as these are
hallmarks of anastomotic leakage.
Aim
To find biomarkers that accurately detect anastomotic leakage at an early time-point.
Methods
In 50 patients (6 with anastomotic leakage (AL), confirmed by laparotomy or
extraluminal contrast on CT) undergoing scheduled colorectal surgery with primary
anastomosis, plasma samples were collected preoperatively, and daily after surgery
until discharge from the hospital. The inflammatory markers C-reactive protein (CRP),
calprotectin, and IL-6; and the markers of gut damage intestinal fatty acid binding
protein (I-FABP), liver fatty acid binding protein (L-FABP), and ileal lipid binding
protein (ILBP) were measured by ELISA. Diagnostic accuracy of single markers or
combinations of markers was analyzed by ROC curve analysis.
Results
CRP at postoperative day (POD) 3 predicted AL with sensitivity, 80%; specificity,
75%; positive likelihood ratio (LR+), 3.20 (95% confidence interval (CI), 1.10 – 9.35);
negative likelihood ratio (LR-), 0.27 (95% CI, 0.04 – 1.61); p=0.03. IL-6 at POD 3
yielded comparable results, and calprotectin on POD 3 predicted AL with sensitivity,
100%; specificity, 75%; LR+ 4.00 (95% CI, 1.35 – 8.59); LR-, 0.00 (95% CI, 0.01 –
1.67); p=0.02. I-FABP levels at POD 3 predicted AL with sensitivity, 83%; specificity,
81%; LR+, 4.37 (95% CI, 1.85 – 10); LR-, 0.21 (95% CI, 0.04 – 1.25); p=0.03. LFABP and ILBP levels were not statistically different between groups. Combination of
calprotectin and I-FABP levels on POD 3 yielded highest accuracy: sensitivity, 100%;
specificity, 91%; LR+, 11 (95% CI, 1.61 – 34); LR-, 0.00 (95% CI, 0.01 – 1.37);
p=0.002.
Conclusion
The inflammatory markers CRP, IL-6 and calprotectin predict anastomotic leakage
with reasonable accuracy on day 3 following colorectal surgery. When combining with
I-FABP, a marker of intestinal epithelial damage, accuracy increases drastically. This
pleads for implementation of these markers in daily practice.