To Örebro University

Regional anesthesia may prolong survival following surgery for different types of cancers. The mechanisms behind this are unclear but direct effects on cancer cells by local anesthetics (LA) have been suggested. The aim of this study was to investigate if lidocaine or ropivacaine have a dose-dependent effect on the cell viability and proliferation of a primary and a secondary colon carcinoma cell line in vitro. The colon cancer cell lines SW480 derived from primary tumor and SW620 from a metastatic site in the same patient were exposed to increasing concentrations of lidocaine and ropivacaine (5-1,000 mu M). Cell viability was measured using CellTiter-Blue((R)) and cell proliferation by PKH67 after exposure for up to 72 h. Cell viability was significantly reduced by ropivacaine at the highest concentration (1,000 mu M) after 48 and 72 h in the cell line SW480 and at 72 h in SW620. Exposure to lidocaine did not show any significant reduction in cell viability. Notably, low concentrations of both lidocaine and ropivacaine significantly increased cell viability after 48 and 72 h in SW620. Cell proliferation was significantly reduced by 1,000 mu M lidocaine in SW480 and by 1,000 mu M ropivacaine in SW620. In summary, both lidocaine and ropivacaine showed an anti-proliferative effect in the colon cancer cell lines at high concentrations and after prolonged exposure to LA in vitro. Our findings also indicate that lower concentrations promote cell viability in the metastatic cell line.

AIM: Epidural analgesia reduces the surgical stress response. However, its effect on pro- and anti-inflammatory cytokines in the genesis of inflammation following major abdominal surgery remains unclear. Our main objective was to elucidate whether perioperative epidural analgesia prevents the inflammatory response following colorectal cancer surgery.

METHODS: 96 patients scheduled for open or laparoscopic surgery were randomized to epidural analgesia (group E) or patient controlled intravenous analgesia (group P). Surgery and anaesthesia were standardized in both groups. Plasma cortisol, insulin and serum cytokines (IL-1β,IL-4,IL-5,IL-6,IL-8,IL-10,IL-12p70,IL-13,TNFα,IFNγ,GM-CSF,PGE2 and VEGF) were measured preoperatively (T0), 1-6 hours postoperatively (T1) and 3-5 days postoperatively (T2). Mixed model analysis was used, after logarithmic transformation when appropriate, for analyses of cytokines and stress markers.

RESULTS: There were no significant differences in any serum cytokine concentration between groups P and E at any time point except in IL-10 which was 87% higher in group P (median and range 4.1 (2.3-9.2) pg/ml,) compared to group E (2.6 (1.3-4.7) pg/ml) (p=0.002) at T1. There was no difference in plasma cortisol and insulin between the groups at any time point after surgery. Significant difference in median serum cytokine concentration was found between open and laparoscopic surgery with higher levels of IL-6,IL-8 and IL-10 at T1 in patients undergoing open surgery compared to laparoscopic surgery. No difference in serum cytokine concentration was detected between the groups or between the surgical technique at T2.

CONCLUSIONS: Open surgery, compared to laparoscopic surgery, has greater impact on these inflammatory mediators than epidural analgesia vs. intravenous analgesia. This article is protected by copyright. All rights reserved.