Peritoneal Cytokines as Early Biomarkers of Colorectal Anastomotic Leakage Following Surgery for Colorectal Cancer: A Meta-Analysis

Abstract

BackgroundPostoperative colorectal anastomotic leakage (CAL) is a devastating complication following colorectal resection. However, the diagnosis of anastomotic leakage is often delayed because the current methods of identification are unable to achieve 100% clinical sensitivity and specificity. This meta-analysis aimed to evaluate the predictive value of peritoneal fluid cytokines in the detection of CAL following colorectal surgery.MethodsA comprehensive search was conducted on PubMed, Embase, Cochrane Library, and Web of Science before June 2021 to retrieve studies regarding peritoneal fluid cytokines as early markers of CAL. Pooled analyses of interleukin (IL)-1β, IL-6, IL-10, and tumor necrosis factor (TNF) were performed. The means (MD) and standard deviations (SD) of the peritoneal fluid cytokines were extracted from the included studies. Review Manager Software 5.3 was used for data analysis.ResultsWe included eight studies with 580 patients, among which 85 (14.7%) and 522 (44.5%) were evaluated as the CAL and non-CAL groups, respectively. Compared to the non-CAL group, the CAL group had significantly higher peritoneal IL-6 levels on postoperative day (POD) 1–3 (P = 0.0006, 0.0002, and 0.002, respectively) and slightly higher TNF levels on POD 4 (P = 0.0002). Peritoneal levels of IL-1β and IL-10 were not significantly different between the two groups in this study.ConclusionPeritoneal IL-6 levels can be a diagnostic marker for CAL following colorectal surgery, whereas the value of TNF needs further exploration in the future.Systematic Review Registration[https://www.crd.york.ac.uk/prospero/#myprospero], PROSPERO (CRD42021274973)

Serum and peritoneal biomarkers for the early prediction of symptomatic anastomotic leakage in patients following laparoscopic low anterior resection: A single‐center prospective cohort study

“…The possible reasons for this opposite result are mainly inconsistent definitions of AL and differences in inclusion criteria after careful analysis. Moreover, the updated high-quality meta-analysis 36 of eight studies further confirmed that peritoneal IL-6 levels could be used as a diagnostic marker for AL after colorectal surgery. In response to surgical stress, proinflammatory cytokines, including IL-6 and TNF-α, released from macrophages could produce an inflammatory reaction.…”

Diagnostic accuracy of interleukin-6 in multiple diseases: An umbrella review of meta-analyses

“…The limited sample size, combined with the potential risk of bias due to inconsistent criteria for defining PJI in relation to the indicators analyzed alongside IL-6, could potentially compromise the validity of the findings. In addition to conditions other than PJI, Qi et al studied postoperative patients with colorectal cancer and found that peritoneal IL-6 levels were significantly higher in the colorectal anastomotic leakage (CAL) group 1–3 days postoperatively compared to the non-CAL group (P = 0.0006, 0.0002, 0.002), suggesting that peritoneal IL-6 levels might be used as a diagnostic indicator of CAL after colorectal surgery [ 76 ]. While our umbrella review covered the majority of infectious and injurious diseases (55.9%), only Yao et al for bacterial meningitis and Shahkar et al and Qiu et al for neonatal sepsis received a "Moderate" rating in GRADE; all other meta-analyses were judged as "Low" or "Very low" in both GRADE and AMSTAR-2 [ [40] , [53] , [56] ].…”

Inflammatory biomarker signatures in post-surgical drain fluid may detect anastomotic leaks within 48 hours of colorectal resection

“…Consequently, when measured in blood it is a non-specific marker of systemic inflammation 19 . Peritoneal IL-6 has been measured before in AL studies and has been proposed as predictive marker for the presence of AL in patients after surgery in isolation 20 . It is broadly successful, with sensitivities and specificities in line with our measurements, but is insufficiently accurate to be used in isolation.…”