Impact of epidural analgesia on the systemic biomarker response after hepatic resection

Abstract

// Diego Vicente 1, 2 , Miguel Patino 2, 4 , Rebecca Marcus 1 , Heather Lillmoe 1 , Preparim Limani 1 , Timothy Newhook 1 , Andy Lee 1 , Ching-Wei Tzeng 1 , Yun Segraves-Chun 1 , David Tweardy 3 , Vijaya Gottumukkala 4 , Jean-Nicolas Vauthey 1 , Thomas Aloia 1 and Juan P. Cata 2, 4 1 Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA 2 Anesthesiology and Surgical Oncology Research Group, Houston, TX, USA 3 Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA 4 Department of Anesthesiology and Perioperative Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA Correspondence to: Juan P. Cata, email: jcata@mdanderson.org Keywords: analgesia; epidural; cytokines Received: October 09, 2018      Accepted: December 22, 2018      Published: January 15, 2019 ABSTRACT Background: Perioperative inflammation is associated with poor oncologic outcomes. Regional analgesia has been shown mitigate some of these inflammatory changes and be associated with better oncologic outcomes in patients with hepatic malignancies. The mechanism for this effect, however, remains unclear. The authors sought to compare systemic biomarker concentrations in a comprehensive and oncologically relevant panel in the perioperative setting between patients undergoing thoracic epidural analgesia (TEA) and intra-venous patient- controlled analgesia (IV-PCA) for resection of hepatic metastatic disease. Results: Clinicopathologic variables and baseline biomarkers were similar between TEA ( n = 46) and IV-PCA ( n = 16) groups. Of the biomarkers which were significantly changed from baseline, there was a lower fold change from baseline in the TEA patients compared to IV-PCA including IL-6 (13.5vs19.1), MCP-1 (1.9vs3.0), IL-8 (2.4vs3.0), and Pentraxin-3 (10.8vs15.6). Overall decreased systemic concentrations of TGFb signaling were noted in TEA patients on POD1 TGFb3 (243.2 vs. 86.0, p = 0.005), POD3 TGFb1 (6558.0 vs. 2063.3, p = 0.004), POD3 TGFb2 (468.3 vs. 368.9, p = 0.036), POD3 TGFb3 (132.2 vs. 77.8, p = 0.028), and POD5 TGFb3 (306.5 vs. 92.2, p = 0.032). POD1 IL-12p70 concentrations were significantly higher in TEA patients (8.3 vs. 1.6, p = 0.024). Conclusion: Epidural analgesia damped the postoperative inflammatory response and systemic immunosuppressive signaling, as well as promoted Th1 systemic signaling early in the post-operative period after hepatic resection for metastatic disease. These differences elaborate on known mechanisms for improved oncologic outcomes with regional anesthesia, and may be considered for biomarker monitoring of effective regional anesthesia in oncologic surgery. Materials and Methods: Patient data, including clinicopathologic variables were collected for this study from the database of a randomized controlled trial comparing perioperative outcomes in patients undergoing hepatic resection with TEA vs. IV-PCA. Patients undergoing resection for metastatic disease were selected for this study. Plasma concentrations (pg/mL) of well-studied biomarkers (IL-1b/2/4/5/6/7/8/10/12p70/13/17, MCP-1 IFNγ, TNFα, MIP-1b, GM-CSF, G-CSF, VEGF, Resistin, TGFb1, TGFb2, and TGFb3), as well as novel perioperative markers (CXCL12, CXCL10, Omentin-1, sLeptin R, Vaspin, Pentraxin-3, Galactin-3, FGF-23, PON-1, FGF-21) were measured preoperatively, and on postoperative day (POD)1, POD3, and POD5 using multiplex bead assays. Clinicopathologic variables and perioperative variations in these biomarkers were compared between TEA vs IV-PCA groups.