A multicentre cohort study of serum and peritoneal biomarkers to predict anastomotic leakage after rectal cancer resection
Sparreboom, C L; Komen, N; Rizopoulos, D; Verhaar, A P; Dik, W A; Wu, Z; van Westreenen, H L; Doornebosch, P G; Dekker, J W T; Menon, A G; Daams, F; Lips, D; van Grevenstein, W M U; Karsten, T M; Bayon, Y; Peppelenbosch, M P; Wolthuis, A M; D'Hoore, A; Lange, J F
(2020) Colorectal Disease, volume 22, issue 1, pp. 36 - 45
(Article)
Abstract
AIM: Anastomotic leakage (AL) is one of the most feared complications after rectal resection. This study aimed to assess a combination of biomarkers for early detection of AL after rectal cancer resection. METHOD: This study was an international multicentre prospective cohort study. All patients received a pelvic drain after rectal
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cancer resection. On the first three postoperative days drain fluid was collected daily and C-reactive protein (CRP) was measured. Matrix metalloproteinase-2 (MMP2), MMP9, glucose, lactate, interleukin 1-beta (IL1β), IL6, IL10, tumour necrosis factor alpha (TNFα), Escherichia coli, Enterococcus faecalis, lipopolysaccharide-binding protein and amylase were measured in the drain fluid. Prediction models for AL were built for each postoperative day using multivariate penalized logistic regression. Model performance was estimated by the c-index for discrimination. The model with the best performance was visualized with a nomogram and calibration was plotted. RESULTS: A total of 292 patients were analysed; 38 (13.0%) patients suffered from AL, with a median interval to diagnosis of 6.0 (interquartile ratio 4.0-14.8) days. AL occurred less often after partial than after total mesorectal excision (4.9% vs 15.2%, P = 0.035). Of all patients with AL, 26 (68.4%) required reoperation. AL was more often treated by reoperation in patients without a diverting ileostomy (18/20 vs 8/18, P = 0.03). The prediction model for postoperative day 1 included MMP9, TNFα, diverting ileostomy and surgical technique (c-index = 0.71). The prediction model for postoperative day 2 only included CRP (c-index = 0.69). The prediction model for postoperative day 3 included CRP and MMP9 and obtained the best model performance (c-index = 0.78). CONCLUSION: The combination of serum CRP and peritoneal MMP9 may be useful for earlier prediction of AL after rectal cancer resection. In clinical practice, this combination of biomarkers should be interpreted in the clinical context as with any other diagnostic tool.
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Keywords: Anastomotic leakage, biomarkers, drain fluid, early detection, rectal resection, Gastroenterology, Journal Article
ISSN: 1462-8910
Publisher: Wiley-Blackwell
Note: © 2019 The Authors. Colorectal Disease published by John Wiley & Sons Ltd on behalf of Association of Coloproctology of Great Britain and Ireland. Funding Information: We would like to thank all patients who participated in this study. We are grateful to everyone in the department of surgery and laboratories of all participating hospitals: Havenziekenhuis, Rotterdam, the Netherlands, IJsselland Ziekenhuis, Capelle aan den Ijssel, the Netherlands, Reinier de Graaf Gasthuis, Delft, the Netherlands, Isala, Zwolle, the Netherlands, VU University Medical Center, Amsterdam, the Netherlands, University Medical Center Utrecht, Utrecht, the Netherlands, Jeroen Bosch Ziekenhuis, Den Bosch, the Netherlands, OLVG Oost, Amsterdam, the Netherlands, University Hospital Leuven, Leuven (Mrs I. Terrasson), Belgium and University Hospital Antwerpen, Antwerp, Belgium. We would also like to thank all co‐workers at the Department of Immunology, Gastroenterology and Clinical Chemistry of the Erasmus MC University Medical Center. This study was funded by Medtronic. Publisher Copyright: © 2019 The Authors. Colorectal Disease published by John Wiley & Sons Ltd on behalf of Association of Coloproctology of Great Britain and Ireland.
(Peer reviewed)