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©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
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.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
https://creativecommons.org/Licenses/by-nc/4.0/ 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
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.
