Utility of C-reactive protein as predictive biomarker of anastomotic leak after minimally invasive esophagectomy
Early detection of anastomotic leakage after esophagectomy has the potential to reduce morbidity and mortality. Prompt suspicion of leak may help to exclude patients from fast-track protocols, thereby avoiding early oral feeding and early hospital discharge which could aggravate the prognosis of a clinically occult leak.
Patients and methods
Observational retrospective cohort study. Patients with diagnosis of esophageal cancer who underwent elective minimally invasive esophagectomy were included. The following data were collected: age, gender, BMI, comorbidities, ASA score, tumor histology, TNM staging, use of neo-adjuvant therapy, type of operation, operative time, morbidity, and 90-day mortality. A panel of biomarkers including C-reactive protein (CRP), procalcitonin (PCT), white blood cells (WBC), and percentage of neutrophils (PN) were measured at baseline and on postoperative days 3, 5, and 7.
Two hundred forty-three patients operated between 2012 and 2017 were included in the study. Anastomotic leakage occurred in 29 patients. There was a statistical association over time between anastomotic leakage and CRP (p < 0.001), PCT (p < 0.001), WBC (p = 0.019), and PN (p = 0.007). The cut-off value of CRP on POD 5 was 8.3 mg/dL, AUC = 0.818, negative LR = 0.176.
Increased serum CRP, PCT, WBC, and PN after minimally invasive esophagectomy are associated with anastomotic leakage. A CRP value lower than 8.3 mg/dL, combined with reassuring clinical and radiological signs, may be useful to exclude leakage on postoperative day 5.
KeywordsEsophagus Esophagectomy Anastomotic leakage C-reactive protein
This work was supported by AIRES (Associazione Italiana Ricerca Esofago).
Authorship EA, GB, MM, ST, PM, AS, EC, and LB participated in the acquisition, analysis, or interpretation of data for the work and drafting or revising it critically for important intellectual content; gave final approval of the version to be published; and agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity in any part of the work are appropriately investigated and resolved.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committee and with 1964 Helsinki declaration and its later amendments.
Informed consent was obtained from all individual participants included in the study.
- 1.Schmidt HM, Gisbertz SS, Moons J, Rouvelas I, Kauppi J, Brown A, Asti E, Luyer M, Lagarde SM, Berlth F, Philippron A, Bruns C, Hölscher A, Schneider PM, Raptis DA, Henegouwen MIB, Nafteux P, Nilsson M, Räsanen J, Palazzo F, Rosato E, Mercer S, Bonavina L, Nieuwenhuijzen G, Wijnhoven BPL, Schröder W, Pattyn P, Grimminger PP, Gutschow CA (2017) Defining benchmarks for transthoracic esophagectomy. A multicenter analysis of total minimally invasive esophagectomy in low risk patients. Ann Surg 266(5):814–821. https://doi.org/10.1097/SLA.0000000000002445 CrossRefPubMedGoogle Scholar
- 5.Biere SS, van Berge Henegouwen MI, Bonavina L, Rosman C, Roig Garcia J, Gisbertz SS, van der Peet DL, Cuesta MA (2017) Predictive factors for post-operative respiratory infections after esophagectomy for esophageal cancer: outcome of randomized trial. J Thorac Dis 9:S861–S867CrossRefPubMedPubMedCentralGoogle Scholar
- 10.Park JK, Kim JJ, Moon SW (2017) C-reactive protein for the early prediction of anastomotic leak after esophagectomy in both neo-adjuvant and non-neoadjuvant therapy case: a propensity score matching analysis. J Thorac Dis 9(10):3963–3702Google Scholar
- 14.Fitzmaurice GM, Laird NM, Ware JH (2011) Applied longitudinal analysis. Wiley, HobokenGoogle Scholar
- 16.Agresti A, Coull BA (1998) Approximate is better than “exact” for interval estimation of binomial proportions. Am Stat 52:119–126Google Scholar
- 19.Sloane P, Slatt L, Ebell NH, Smith MA, Power DV, Viera AJ (2012) Essentials of family medicine, 6th edn. Walters Kluwer. Health, PhiladelphiaGoogle Scholar
- 20.R Core Team Development (2008) R: a language and environment for statistical computing. R Foundation for Statistical Computing, ViennaGoogle Scholar
- 22.Motoyama S, Miura M, Hinai Y, Maruyama K, Usami S, Nakatsu T, Saito H, Minamiya Y, Suzuki T, Ogawa JI (2009) C-reactive protein 1059G>C genetic polymorphism influences serum C-reactive protein levels after esophagectomy in patients with thoracic esophageal cancer. J Am Coll Surg 209:477–483CrossRefPubMedGoogle Scholar
- 23.Frees EW (2006) Longitudinal and panel data: analysis and applications in the social sciences. J Am Stat Assoc 101(March):402–402. https://doi.org/10.2307/30047489