• M Z Johnson, P D Crowley, A G Foley, C Xue, C Connolly, H C Gallagher, and D J Buggy.
• Department of Anaesthesia, Mater University Hospital, School of Medicine, University College Dublin, Dublin, Ireland; School of Medicine, Conway Institute for Biomolecular and Biomedical Research, University College Dublin, Dublin, Ireland; EU COST Action 15204, Euro-Periscope. Electronic address: markzjohnson@gmail.com.
• Br J Anaesth. 2018 Jul 1; 121 (1): 76-85.

BackgroundBreast cancer accounts for 7% of female cancer deaths, usually attributable to metastasis. While surgery is a mainstay of treatment, perioperative interventions may influence risk of metastasis during breast tumour resection. Amide local anaesthetics influence cancer cell biology via numerous mechanisms in vitro, but in vivo data is lacking. We aimed to test the hypothesis that perioperative lidocaine reduces pulmonary metastasis after inhalation and i.v. anaesthesia in the 4T1 murine breast cancer model.Methods4T1 Cancer cells were injected into the mammary fat-pad of immunocompetent BALB/c female mice. After 7 days, the resultant tumour was excised under either sevoflurane or ketamine/xylazine anaesthesia with or without perioperative i.v. lidocaine (1.5 mg kg-1 bolus followed by 25 min infusion 2 mg kg-1 h-1). Fourteen days post-surgery, posthumous lung and liver specimens were examined for metastasis. Pro-inflammatory and pro-metastatic cytokines were profiled in post-mortem serum from a small number of the mice.ResultsPrimary tumour diameter was similar between groups. Lidocaine reduced lung metastatic colony count vs sevoflurane alone; median (inter-quartile range) 0 (0-2) compared with 22.5 (0-481), P=0.02 and reduced the proportion of animals with pulmonary metastasis (28.5% compared with 52.5%, P=0.04). In mice receiving ketamine-xylazine, lidocaine did not decrease the overall colony count: 60 (26-123) compared with 23.5 (0-225), P=0.43, but increased the proportion of animals with pulmonary metastasis (100% compared with 50%, P<0.01). Post-mortem serum analysis demonstrated reduced pro-inflammatory and angiogenic cytokine expression in animals without metastasis which received lidocaine with sevoflurane.ConclusionsIn this 4T1 murine model of breast cancer, lidocaine decreased pulmonary metastasis when combined with sevoflurane anaesthesia, perhaps via anti-inflammatory and anti-angiogenic effects. It had no such effect in mice given ketamine anaesthesia.Copyright © 2018 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.

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