A multicentre cohort study of serum and peritoneal biomarkers to predict anastomotic leakage after rectal cancer resection

C. L. Sparreboom, N. Komen, D. Rizopoulos, A. P. Verhaar, W. A. Dik, Z. Wu, H. L. van Westreenen, P. G. Doornebosch, J. W. T. Dekker, A. G. Menon, F. Daams, D. Lips, W. M. U. van Grevenstein, T. M. Karsten, Y. Bayon, M. P. Peppelenbosch, A. M. Wolthuis, A. D'Hoore, J. F. Lange

Research output: Contribution to journalArticleAcademicpeer-review

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 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.
Original languageEnglish
JournalColorectal Disease
DOIs
Publication statusPublished - 2019

Cite this

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. / A multicentre cohort study of serum and peritoneal biomarkers to predict anastomotic leakage after rectal cancer resection. In: Colorectal Disease. 2019.
@article{c9b255e2157a40718930bd785bf2c607,
title = "A multicentre cohort study of serum and peritoneal biomarkers to predict anastomotic leakage after rectal cancer resection",
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 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.",
author = "Sparreboom, {C. L.} and N. Komen and D. Rizopoulos and Verhaar, {A. P.} and Dik, {W. A.} and Z. Wu and {van Westreenen}, {H. L.} and Doornebosch, {P. G.} and Dekker, {J. W. T.} and Menon, {A. G.} and F. Daams and D. Lips and {van Grevenstein}, {W. M. U.} and Karsten, {T. M.} and Y. Bayon and Peppelenbosch, {M. P.} and Wolthuis, {A. M.} and A. D'Hoore and Lange, {J. F.}",
year = "2019",
doi = "10.1111/codi.14789",
language = "English",
journal = "Colorectal Disease",
issn = "1462-8910",
publisher = "Wiley-Blackwell",

}

Sparreboom, CL, Komen, N, Rizopoulos, D, Verhaar, AP, Dik, WA, Wu, Z, van Westreenen, HL, Doornebosch, PG, Dekker, JWT, Menon, AG, Daams, F, Lips, D, van Grevenstein, WMU, Karsten, TM, Bayon, Y, Peppelenbosch, MP, Wolthuis, AM, D'Hoore, A & Lange, JF 2019, 'A multicentre cohort study of serum and peritoneal biomarkers to predict anastomotic leakage after rectal cancer resection' Colorectal Disease. https://doi.org/10.1111/codi.14789

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.

In: Colorectal Disease, 2019.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - A multicentre cohort study of serum and peritoneal biomarkers to predict anastomotic leakage after rectal cancer resection

AU - Sparreboom, C. L.

AU - Komen, N.

AU - Rizopoulos, D.

AU - Verhaar, A. P.

AU - Dik, W. A.

AU - Wu, Z.

AU - van Westreenen, H. L.

AU - Doornebosch, P. G.

AU - Dekker, J. W. T.

AU - Menon, A. G.

AU - Daams, F.

AU - Lips, D.

AU - van Grevenstein, W. M. U.

AU - Karsten, T. M.

AU - Bayon, Y.

AU - Peppelenbosch, M. P.

AU - Wolthuis, A. M.

AU - D'Hoore, A.

AU - Lange, J. F.

PY - 2019

Y1 - 2019

N2 - 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 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.

AB - 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 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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UR - https://www.ncbi.nlm.nih.gov/pubmed/31344302

U2 - 10.1111/codi.14789

DO - 10.1111/codi.14789

M3 - Article

JO - Colorectal Disease

JF - Colorectal Disease

SN - 1462-8910

ER -