title: Accurate prediction of anastomotic leakage after colorectal surgery using plasma markers for intestinal damage and inflammation.
abstract: 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.
  
  
  METHODS
  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.
authors.affiliation: Department of Surgery, Maastricht University Medical Center and Nutrim School for Nutrition, Toxicology and Metabolism, Maastricht University, Maastricht, The Netherlands. Electronic address: k.reisinger@maastrichtuniversity.nl.
authors.forename: Kostan W
authors.initials: KW
authors.lastname: Reisinger
authors.affiliation: Department of Surgery, Maastricht University Medical Center and Nutrim School for Nutrition, Toxicology and Metabolism, Maastricht University, Maastricht, The Netherlands.
authors.forename: Martijn
authors.initials: M
authors.lastname: Poeze
authors.affiliation: Department of Surgery, Orbis Medical Center, Sittard, The Netherlands.
authors.forename: Karel W E
authors.initials: KW
authors.lastname: Hulsewé
authors.affiliation: Department of Clinical Chemistry, Orbis Medical Center, Sittard, The Netherlands.
authors.forename: Bernadette A
authors.initials: BA
authors.lastname: van Acker
authors.affiliation: Department of Surgery, Maastricht University Medical Center and Nutrim School for Nutrition, Toxicology and Metabolism, Maastricht University, Maastricht, The Netherlands.
authors.forename: Annemarie A
authors.initials: AA
authors.lastname: van Bijnen
authors.affiliation: Department of Surgery, Orbis Medical Center, Sittard, The Netherlands.
authors.forename: Anton G M
authors.initials: AG
authors.lastname: Hoofwijk
authors.affiliation: Department of Surgery, Orbis Medical Center, Sittard, The Netherlands.
authors.forename: Jan H M B
authors.initials: JH
authors.lastname: Stoot
authors.affiliation: Department of Surgery, Maastricht University Medical Center and Nutrim School for Nutrition, Toxicology and Metabolism, Maastricht University, Maastricht, The Netherlands; Department of Surgery, Orbis Medical Center, Sittard, The Netherlands.
authors.forename: Joep P M
authors.initials: JP
authors.lastname: Derikx
mesh_terms: D000368:Aged; D057868:Anastomotic Leak / Q000097:blood / Q000175:diagnosis* / Q000453:epidemiology; D015415:Biomarkers / Q000097:blood*; D003107:Colorectal Surgery / Q000009:adverse effects*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D007249:Inflammation / Q000097:blood / Q000175:diagnosis*; D008297:Male; D009426:Netherlands / Q000453:epidemiology; D011184:Postoperative Period; D011237:Predictive Value of Tests; D011379:Prognosis; D012372:ROC Curve; D015203:Reproducibility of Results
chemical_list: D015415:Biomarkers