Use of C-reactive Protein for the Early Prediction of Anastomotic Leak After Esophagectomy: Systematic Review and Bayesian Meta-analysis

Background: Early suspicion, diagnosis, and timely treatment of anastomotic leak after esophagectomy is essential. Retrospective studies have investigated the role of C-reactive protein (CRP) as early marker of anastomotic leakage. The aim of this systematic review and meta-analysis was to evaluate the predictive value of CRP after esophageal resection.

Methods: A literature search was conducted to identify all reports including serial postoperative CRP measurements to predict anastomotic leakage after elective open or minimally invasive esophagectomy. Fully Bayesian meta-analysis was carried out using random-effects model for pooling diagnostic accuracy measures along with CRP cut-off values at different postoperative day.

Results: Five studies published between 2012 and 2018 met the inclusion criteria. Overall, 850 patients were included. Ivor-Lewis esophagectomy was the most common surgical procedure (72.3%) and half of the patients had squamous-cell carcinoma (50.4%). The estimated pooled prevalence of anastomotic leak was 11% (95% CI = 8-14%). The serum CRP level on POD3 and POD5 had comparable diagnostic accuracy with a pooled area under the curve of 0.80 (95% CIs 0.77-0.92) and 0.83 (95% CIs 0.61-0.96), respectively. The derived pooled CRP cut-off values were 17.6 mg/dl on POD 3 and 13.2 mg/dl on POD 5; the negative likelihood ratio were 0.35 (95% CIs 0.096-0.62) and 0.195 (95% CIs 0.04-0.52).

Conclusion: After esophagectomy, a CRP value lower than 17.6 mg/dl on POD3 and 13.2 mg/dl on POD5 combined with reassuring clinical and radiological signs may be useful to rule-out leakage. In the context of ERAS protocols, this may help to avoid contrast radiological studies, anticipate oral feeding, accelerate hospital discharge, and reduce costs.