Freeman James, Crowley Peter D, Foley Andrew G, Gallagher Helen C, Iwasaki Masae, Ma Daqing, Buggy Donal J
Department of Anaesthesia, Mater University Hospital, Dublin 7, Ireland.
Conway Institute for Biomedical Sciences, School of Medicine, University College Dublin, Dublin 4, Ireland.
Cancers (Basel). 2019 May 1;11(5):613. doi: 10.3390/cancers11050613.
Addressing the hypothesis that anaesthetic-analgesic technique during cancer surgery might influence recurrence or metastatic spread is a research priority. Propofol, which has anti-inflammatory properties in vitro, is clinically associated with reduced risk of cancer recurrence compared with sevoflurane anaesthesia in retrospective studies. Amide local anaesthetics, such as lidocaine, have cancer inhibiting effects in vitro. Steroids have anti-inflammatory and immunosuppressive effects and are associated with improved recovery after major non-cancer surgery. We compared the effects of propofol, lidocaine and methylprednisolone on postoperative metastasis in a murine model of breast cancer surgery under sevoflurane anaesthesia. 4T1 tumour cells were introduced into the mammary fat-pad of female BALB/c mice and the resulting tumour resected seven days later under general anaesthesia with sevoflurane. Mice ( = 72) were randomized to four treatment groups: Sevoflurane alone (control); Propofol group received 5 mg.kg; Lidocaine group received 1.5 mg.kg followed by 2 mg.kg.h infusion; Methylprednisolone group received 30 mg.kg methylprednisolone. The primary outcome measure was pulmonary metastasis colony count, as assessed by in-vitro proliferation, two weeks post-operatively. This was achieved by treating the post-mortem lung tissue with collagenase IV, straining and culturing for 14 days prior to colony count. Compared with control, lidocaine and propofol each individually reduced pulmonary metastasis colonies; mean (SD) 846 (±581) vs. 88 (±52) vs. 34 (±44) respectively, ( = 0.0001 and = 0.0001). Methylprednisolone increased lung metastasis, 2555 (±609) vs. 846 (±581), = 0.0001. Post-operative hepatic metastatic disease and serum interleukin-6 and vascular endothelial growth factor levels were similar in all groups. In conclusion, in a murine model of breast cancer surgery during sevoflurane anaesthesia, propofol and lidocaine each decreased pulmonary metastasis, while methylprednisolone increased it.
验证癌症手术期间麻醉镇痛技术可能影响复发或转移扩散这一假说，是一项研究重点。丙泊酚在体外具有抗炎特性，回顾性研究表明，与七氟烷麻醉相比，其在临床上与降低癌症复发风险相关。酰胺类局部麻醉药，如利多卡因，在体外具有癌症抑制作用。类固醇具有抗炎和免疫抑制作用，与非癌症大手术后恢复情况改善有关。我们在七氟烷麻醉下的乳腺癌手术小鼠模型中，比较了丙泊酚、利多卡因和甲泼尼龙对术后转移的影响。将4T1肿瘤细胞植入雌性BALB/c小鼠的乳腺脂肪垫，7天后在七氟烷全身麻醉下切除产生的肿瘤。小鼠（n = 72）被随机分为四个治疗组：单纯七氟烷（对照组）；丙泊酚组接受5mg·kg；利多卡因组接受1.5mg·kg，随后以2mg·kg·h输注；甲泼尼龙组接受30mg·kg甲泼尼龙。主要结局指标是术后两周通过体外增殖评估的肺转移集落计数。这是通过用IV型胶原酶处理尸检肺组织、过滤并在集落计数前培养14天来实现的。与对照组相比，利多卡因和丙泊酚各自单独降低了肺转移集落；平均值（标准差）分别为846（±581）、88（±52）、34（±44），（P = 0.0001和P = 0.0001）。甲泼尼龙增加了肺转移，2555（±609）对846（±581），P = 0.0001。所有组术后肝转移疾病以及血清白细胞介素-6和血管内皮生长因子水平相似。总之，在七氟烷麻醉下的乳腺癌手术小鼠模型中，丙泊酚和利多卡因均降低了肺转移，而甲泼尼龙则增加了肺转移。
