title: A Systematic Review of the Modifying Effect of Anaesthetic Drugs on Metastasis in Animal Models for Cancer.
abstract: Distant metastasis or local recurrence after primary tumour resection remain a major clinical problem. The anaesthetic technique used during oncologic surgery is suggested to influence the metastatic process. While awaiting the results of ongoing randomised controlled trials (RCTs), we have analyzed the evidence regarding the influence of anaesthetic drugs on experimental tumour metastasis in animal studies.
  
  
  
  PubMed and Embase were searched until April 21st, 2015. Studies were included in the systematic review when they 1) assessed the effect of an anaesthetic drug used in clinical practice on the number or incidence of metastasis in animal models with experimental cancer, 2) included an appropriate control group, and 3) presented unique data.
  
  
  
  20 studies met the inclusion criteria (published between 1958-2010). Data on number of metastases could be retrieved from 17 studies. These studies described 41 independent comparisons, 33 of which could be included in the meta-analysis (MA). The incidence of metastases was studied in 3 unique papers. From these 3 papers, data on 7 independent comparisons could be extracted and included in the MA. Locally administered local anaesthetics appear to decrease the number of metastases (SMD -6.15 [-8.42; -3.88]), whereas general anaesthetics (RD: 0.136 [0.045, 0.226]), and more specifically volatile anaesthetics (SMD 0.54 [0.24; 0.84]), appear to increase the number and risk of metastases in animal models for cancer.
  
  
  
  Anaesthetics influence the number and incidence of metastases in experimental cancer models. Although more high quality experimental research is necessary, based on the currently available evidence from animal studies, there is no indication to suggest that locally administered local anaesthetics are harmful during surgery in cancer patients. Volatile anaesthetics, however, might increase metastasis in animal models and clinical trials investigating this possibly harmful effect should receive priority. The results of our systematic review in animal studies are broadly consistent with clinical reports that anaesthetic technique does seem to affect the tumour metastasis process.
authors.affiliation: Department of SYstematic Review Centre for Laboratory animal Experimentation (SYRCLE), Radboud University Medical Centre, 6500 HB, Nijmegen, the Netherlands.|Department of Anesthesiology, Pain and Palliative Medicine, Radboud University Medical Centre, 6500 HB, Nijmegen, the Netherlands.
authors.forename: Carlijn R
authors.identifier: 0000-0001-6435-5714
authors.initials: CR
authors.lastname: Hooijmans
authors.affiliation: Department of Anesthesiology, Pain and Palliative Medicine, Radboud University Medical Centre, 6500 HB, Nijmegen, the Netherlands.
authors.forename: Florentine J
authors.initials: FJ
authors.lastname: Geessink
authors.affiliation: Department of SYstematic Review Centre for Laboratory animal Experimentation (SYRCLE), Radboud University Medical Centre, 6500 HB, Nijmegen, the Netherlands.
authors.forename: Merel
authors.initials: M
authors.lastname: Ritskes-Hoitinga
authors.affiliation: Department of Anesthesiology, Pain and Palliative Medicine, Radboud University Medical Centre, 6500 HB, Nijmegen, the Netherlands.
authors.forename: Gert Jan
authors.initials: GJ
authors.lastname: Scheffer
mesh_terms: D000777:Anesthetics / Q000009:adverse effects*; D000818:Animals; D004195:Disease Models, Animal; D006801:Humans; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000601:surgery*; D011183:Postoperative Complications
chemical_list: D000777:Anesthetics