Predictive Ability of C-Reactive Protein in Detecting Short-Term Complications After Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy: A Retrospective Cross-Sectional Study

Background: Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) is a potentially curative treatment for peritoneal carcinomatosis. Objective: The aim of this study was to determine the predictive value of postoperative inflammatory biomarkers in assessing complications after CRS and HIPEC. Methods: A prospective database of 181 patients, who underwent CRS-HIPEC between March 2014 through April 2018 in the Erasmus MC, was retrospectively analyzed. Postoperative complications were defined according to the serious adverse event (SAE) grading system. Levels of C-reactive protein (CRP) and white blood cell (WBC) count were compared between patients with SAE grade < 3 and SAE grade ≥ 3. The area under the receiver operating characteristic curve (AUC) was calculated for CRP and WBC against SAE ≥ 3 and various intra-abdominal complications. Results: SAE ≥ 3 postoperative complications occurred in 50 patients. From the second until the fifth postoperative day (POD), CRP levels were significantly higher (p = 0.023, p < 0.001, p = 0.002, and p = 0.002, respectively) in these patients. CRP concentrations above 166 mg/L on POD3 (AUC 0.75) and 116 mg/L on POD4 (AUC 0.70) were associated with the highest risk of an SAE ≥ 3. Postoperative WBC levels were not significantly different between patients with SAE < 3 and SAE ≥ 3 complications. Conclusion: Data from our hospital suggest that CRP levels that continue to rise after POD2 or that are ≥ 166 mg/L at POD3 or ≥ 116 mg/L at POD4, indicate a considerable risk for developing high-grade SAEs. The cut-off values we found can potentially be used as a threshold for additional diagnostic interventions, after they have been validated in external data

Mesenchymal Stromal Cell-Derived Factors Promote Tissue Repair in a Small-for-Size Ischemic Liver Model but Do Not Protect against Early Effects of Ischemia and Reperfusion Injury

Loss of liver mass and ischemia/reperfusion injury (IRI) are major contributors to postresectional liver failure and small-for-size syndrome. Mesenchymal stromal cell-(MSC-) secreted factors are described to stimulate regeneration after partial hepatectomy. This study investigates if liver-derived MSC-secreted factors also promote liver regeneration after resection in the presence of IRI. C57BL/6 mice underwent IRI of 70% of their liver mass, alone or combined with 50% partial hepatectomy (PH). Mice were treated with MSC-conditioned medium (MSC-CM) or unconditioned medium (UM) and sacrificed after 6 or 24 hours (IRI group) or after 48 hours (IRI + PH group). Blood and liver tissue were analyzed for tissue injury, hepatocyte proliferation, and gene expression. In the IRI alone model, serum ALT and AST levels, hepatic tissue damage, and inflammatory cytokine gene expression showed no significant differences between both treatment groups. In the IRI + PH model, significant reduction in hepatic tissue damage as well as a significant increase in hepatocyte proliferation was observed after MSC-CM treatment. Conclusion. Mesenchymal stromal cell-derived factors promote tissue regeneration of small-for-size livers exposed to ischemic conditions but do not protect against early ischemia and reperfusion injury itself. MSC-derived factors therefore represent a promising treatment strategy for small-for-size syndrome and postresectional liver failure