Usefulness of serum C-reactive protein and calprotectin for the early detection of colorectal anastomotic leakage: A prospective observational study

doi:10.3748/wjg.v28.i24.2758

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World Journal of Gastroenterology

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1007-9327

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

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Observational Study

World J Gastroenterol. Jun 28, 2022; 28(24): 2758-2774
Published online Jun 28, 2022. doi: 10.3748/wjg.v28.i24.2758

Usefulness of serum C-reactive protein and calprotectin for the early detection of colorectal anastomotic leakage: A prospective observational study

Nuno J G Rama, Marlene C C Lages, Maria Pedro S Guarino, Óscar Lourenço, Patrícia C Motta Lima, Diana Parente, Cândida S G Silva, Ricardo Castro, Ana Bento, Anabela Rocha, Fernando Castro-Pocas, João Pimentel

Nuno J G Rama, Patrícia C Motta Lima, Diana Parente, Colorectal Surgical Division, Leiria Hospital Centre, Leiria 2410-021, Portugal

Nuno J G Rama, Anabela Rocha, Fernando Castro-Pocas, Abel Salazar Biomedical Institute (ICBAS), University of Oporto, Oporto 4099-002, Portugal

Nuno J G Rama, Marlene C C Lages, Maria Pedro S Guarino, Cândida S G Silva, Center for Innovative Care and Health Technology (ciTechCare), Polytechnic of Leiria, Leiria 2410-541, Portugal

Óscar Lourenço, Faculty of Economics, CeBER, University of Coimbra, Coimbra 3000-137, Portugal

Ricardo Castro, Ana Bento, Clinical Pathology Division, Leiria Hospital Centre, Leiria 2410-541, Portugal

Anabela Rocha, Surgical Division, Oporto Hospital Centre, Oporto 4099-001, Portugal

Fernando Castro-Pocas, Department of Gastroenterology, Santo António Hospital, Porto Hospital Center, Porto 4099-001, Portugal

Fernando Castro-Pocas, Institute of Biomedical Sciences Abel Salazar, University of Porto, Porto 4099-001, Portugal

João Pimentel, Faculty of Medicine, University of Coimbra, Coimbra 3004-531, Portugal

João Pimentel, Surgical Division, Montes Claros Hospital, Coimbra 3030-320, Portugal

Author contributions: Rama NJM, Guarino MPS, and Lourenço Ó designed the study; Lages MCC, Castro R, Bento A, and Parente D coordinated the data collection process; Lourenço Ó and Silva CSG performed the data analyses; Rama NJM, Motta Lima PC and Guarino MPS prepared the manuscript; Rama NJM, Rocha A, Castro-Poças F, and Pimentel J revised the paper critically; All authors read and approved the final manuscript.

Supported by

the Ministry of Health – Incentive Program for the Integration of Care and Valuation of Patients’ Pathways in the National Health Service of Portugal.

Institutional review board statement: This study was conducted in accordance with the Declaration of Helsinki and was approved by the Local Ethical Committee of the Colorectal Referral Centre, after authorization obtained from the Portuguese Data Protection Authority. This study is registered with the number 9930/2016 and can be consulted at https://drive.google.com/file/d/1BiLxWlvcrqpX4KQrjW4F2codsOOywVF/view?usp=sharing.

Informed consent statement: Informed consent was obtained from all participants included in the study.

Conflict-of-interest statement: The authors have no conflicts of interest to declare.

Data sharing statement: For additional data, Dr. Nuno Rama can be contacted by e-mail at ramanuno@gmail.com.

STROBE statement: The authors have read the STROBE Statement – checklist of items, and the manuscript was prepared and revised according to the STROBE Statement – checklist of items.

Corresponding author: Nuno JG Rama, FEBS, MD, MHSc, Associate Professor, Research Assistant Professor, Surgeon, Colorectal Surgical Division, Leiria Hospital Centre, Rua das Olhalvas, Leiria 2410-021, Portugal. ramanuno@gmail.com

Received: January 13, 2022
Peer-review started: January 13, 2022
First decision: March 8, 2022
Revised: March 22, 2022
Accepted: May 14, 2022
Article in press: May 14, 2022
Published online: June 28, 2022
Processing time: 161 Days and 13.8 Hours

ARTICLE HIGHLIGHTS

Research background

Colorectal anastomotic leakage (CAL) is a major complication in abdominal surgery. Prompt diagnosis can reduce morbidity and mortality associated with this condition. Serum biomarkers have been proposed as predictors of CAL.

Research motivation

Biomarkers such as C-reactive protein (CRP) and white blood cell (WBC) count are frequently requested in the postoperative period of colorectal surgery. However, the usefulness of these and other biomarkers remains unclear.

Research objectives

To assess the role of CRP, WBC, eosinophil cell count, calprotectin (CLP), and procalcitonin in the first 5 postoperative days (PODs) after colorectal surgery, and thus, discuss in what order these biomarkers can be employed in clinical practice.

Research methods

From March 2017 to August 2019, we measured and analyzed five serum biomarkers daily in 396 patients who underwent colorectal surgery. The area under the receiver operating characteristic curve, specificity, sensitivity, positive predictive value (PPV), and negative predictive value (NPV) were used to estimate the best predictive diagnostic performance.

Research results

CRP had an NPV of 98% on POD5. The combination of CLP and CRP measurement presented a high diagnostic accuracy (AUCROC = 0.82) on POD3. We identified a reduction of 5.2 d to the diagnosis of CAL.

Research conclusions

The combination of CRP and CLP demonstrated good diagnostic accuracy. These tests can likely be used to reduce time to CAL detection.

Research perspectives

Further studies should test a warning index score built from selected predictive variables as biomarkers CRP and CLP.