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• W2118582478 abstract "It is getting close to 10 years ago now that Aristomenis Exadaktylos and colleagues1Exadaktylos AK Buggy DJ Moriarty DC Mascha E Sessler DI Can anesthetic technique for primary breast cancer surgery affect recurrence or metastasis?.Anesth. 2006; 105: 660-664Crossref PubMed Scopus (704) Google Scholar published a paper suggesting that choice of anaesthetic technique might influence cancer recurrence risk after breast cancer surgery. This provocative retrospective study led to a rush of similar investigations – all of them retrospective, although some investigators reanalysed data from previous randomized trials (e.g. Myles performed a re-analysis of a subset of patients enrolled in the MASTER trial2Rigg JR Jamrozik K Myles PS et al.Epidural anaesthesia and analgesia and outcome of major surgery: a randomised trial.Lancet. 2002; 359: 1276-1282Abstract Full Text Full Text PDF PubMed Scopus (786) Google Scholar – and did not show an effect of epidural use on abdominal cancer recurrence3Myles PS Peyton P Silbert B et al.Perioperative epidural analgesia for major abdominal surgery for cancer and recurrence-free survival: randomised trial.Br Med J. 2011; 342: d1491Crossref PubMed Scopus (234) Google Scholar). The results of these various reports have been rather confusing, with some papers suggesting that regional anaesthesia or adjuncts such as ketorolac are beneficial, yet others finding no outcome effects at all – at times in the same cancer type (e.g. the use of epidural analgesia in colon cancer,4Christopherson R James KE Tableman M Marshall P Johnson FE Long-term survival after colon cancer surgery: a variation associated with choice of anesthesia.Anesth Analg. 2008; 107: 325-332Crossref PubMed Scopus (221) Google Scholar, 5Gottschalk A Ford JG Regelin CC et al.Association between epidural analgesia and cancer recurrence after colorectal cancer surgery.Anesth. 2010; 113: 27-34Crossref PubMed Scopus (189) Google Scholar or prostate surgery6Biki B Mascha E Moriarty DC Fitzpatrick JM Sessler DI Buggy DJ Anesthetic technique for radical prostatectomy surgery affects cancer recurrence: a retrospective analysis.Anesth. 2008; 109: 180-187Crossref PubMed Scopus (501) Google Scholar, 7Forget P Tombal B Scholtes JL et al.Do intraoperative analgesics influence oncological outcomes after radical prostatectomy for prostate cancer?.Europ J Anaesth. 2011; 28: 830-835Crossref PubMed Scopus (92) Google Scholar). For the clinician, faced with clinical choices to make, this is a baffling dataset to deal with. I have previously pointed out that we have insufficient evidence to suggest changing clinical practice8Durieux ME Anesthesia and cancer recurrence: improved understanding, but no reason for change.Anesth Analg. 2014; 118: 8-9Crossref PubMed Scopus (9) Google Scholar and this standpoint was reiterated recently in a consensus statement from a BJA Workgroup on Cancer and Anaesthesia.9Buggy DJ Borgeat A Cata J et al.Consensus statement from the BJA Workshop on Cancer and Anaesthesia.Br J Anaesth. 2015; 114: 2-3Abstract Full Text Full Text PDF PubMed Scopus (74) Google Scholar But that does not mean that we should not be looking for mechanisms that might explain why anaesthetic technique potentially could influence cancer surgery outcome. Unfortunately, in the basic science arena the results are also confusing and not easily interpreted. When considering how use of regional anaesthesia or adjuncts such as ketorolac might affect recurrence, one possibility that comes to mind is that these techniques would reduce opioid use. Interestingly, opioids have unexpected effects on cancer growth: they stimulate mitogenesis10Gupta K Kshirsagar S Chang L et al.Morphine stimulates angiogenesis by activating proangiogenic and survival-promoting signaling and promotes breast tumor growth.Can res. 2002; 62: 4491-4498PubMed Google Scholar and angiogenesis in tumours,11Farooqui M Li Y Rogers T et al.COX-2 inhibitor celecoxib prevents chronic morphine-induced promotion of angiogenesis, tumour growth, metastasis and mortality, without compromising analgesia.Br J Can. 2007; 97: 1523-1531Crossref PubMed Scopus (182) Google Scholar and in agreement, naloxone prevents tumour growth in animal models.10Gupta K Kshirsagar S Chang L et al.Morphine stimulates angiogenesis by activating proangiogenic and survival-promoting signaling and promotes breast tumor growth.Can res. 2002; 62: 4491-4498PubMed Google Scholar The peripheral opioid antagonist methylnaltrexone similarly prevents lung tumour growth after injection of malignant cells in mice12Mathew B Lennon FE Siegler J et al.The novel role of the mu opioid receptor in lung cancer progression: a laboratory investigation.Anesth Analg. 2011; 112: 558-567Crossref PubMed Scopus (192) Google Scholar and might be a feasible adjunct in the clinical setting. Thus, opioid reduction for a while seemed the main candidate for explaining regional anaesthetic effects on cancer recurrence. But then, concern was raised that the animal models used are not representative of the perioperative situation, and the Consensus Statement mentioned above pointed out that in possibly more relevant models protective effects of opioids may even be seen.9Buggy DJ Borgeat A Cata J et al.Consensus statement from the BJA Workshop on Cancer and Anaesthesia.Br J Anaesth. 2015; 114: 2-3Abstract Full Text Full Text PDF PubMed Scopus (74) Google Scholar It is indicative of the differences of opinion that one of the participants at the conference, Jonathan Moss, ‘did not sign the consensus because he and others have done cellular, molecular and animal work suggesting that opiate antagonism may influence cancer progression in these model systems’13Leung M Link between anesthetic agents, technique and cancer outcomes needs research.Anesth News. 2014; 40 (accessed 6 February 2015)Available from http://www.anesthesiologynews.com/ViewArticle.aspx?d=Policy%2B%26%2BManagement&d_id=3&i=October+2014&i_id=1107&a_id=28364Google Scholar and is commercially developing methylnaltrexone for this purpose. Although I feel it is too early to dismiss a role for opioids completely, what other factors could play a role? Regional techniques and adjuncts also reduce required concentrations of volatile anaesthetics. Might that effect explain their suggested effect on cancer recurrence? Might it be possible that volatile anaesthetics promote cancer recurrence? Two basic science articles in this issue of BJA address this issue. Luo and colleagues14Luo X Zhao H Hennah L et al.Impact of isoflurane on malignant capability of ovarian cancer in vitro.Br J Anaesth. 2015; 114: 831-839Abstract Full Text Full Text PDF PubMed Scopus (74) Google Scholar in this issue, reported the effects of isoflurane (2%) on ovarian cancer cells. They found that the anaesthetic increased tumour markers for cell cycle progression, as well as proliferation and angiogenesis. In addition, cell migration was increased. Shi and colleagues15Shi QY Zhang SJ Liu L et al.Sevoflurane promotes the expansion of glioma stem cells through activation of hypoxia-inducible factors in vitro.Br J Anaesth. 2015; 114: 825-830Abstract Full Text Full Text PDF PubMed Scopus (47) Google Scholar, in this issue, in a similar study, investigated the effects of sevoflurane (2%) on glioma stem cells, and reported that it increased proliferation and markers for proliferation. These data are in agreement with some previous animal studies. As far back as 1997, Moudgil and colleagues16Moudgil GC Singal DP Halothane and isoflurane enhance melanoma tumour metastasis in mice.Canadian J Anaesth = J Canadien D'anesth. 1997; 44: 90-94Crossref PubMed Scopus (53) Google Scholar. reported that 1.3 MAC hour of isoflurane or halothane increased the number of pulmonary metastases after melanoma cell injection in mice by about 2- and 3-fold, respectively. A very interesting study published in BJA in 2009 obtained serum from patients undergoing breast cancer surgery using either a sevoflurane/opioid anaesthetic technique or a propofol/paravertebral block technique. This serum was then added to breast cancer cells in vitro, and their proliferation measured. Whereas serum from sevoflurane-treated patients increased proliferation by 75%, that from propofol-treated patients decreased it by about 25%.17Deegan CA Murray D Doran P Ecimovic P Moriarty DC Buggy DJ Effect of anaesthetic technique on oestrogen receptor-negative breast cancer cell function in vitro.Br J Anaesth. 2009; 103: 685-690Abstract Full Text Full Text PDF PubMed Scopus (109) Google Scholar So is it time to turn down the vaporizer? We need to be careful about not falling into the same trap of overenthusiasm that might have occurred regarding the role of opioids. None of these studies mimics the clinical setting very well. Maybe most importantly, in vitro models as used in the studies published in this issue of BJA remove the cellular environment a cancer cell lives in, and eliminate the tremendous role of the immune system (which itself may be stimulated or inhibited by a variety of perioperative events and drugs). Hence, although these data are important and useful, we can in no way extrapolate them to the clinic. This is not an easy thing to accept for us that work in the operating theatre. That anaesthetic management during potentially curative cancer surgery may affect outcome, and that whether a patient will be alive or dead 10 years later may possibly result from decisions made intraoperatively, is a thought that makes one grasp at any piece of data to try to do things right. But the potential importance of the issue should not blind us to the reality that basic science data and retrospective trials form no basis for clinical decision-making. We will have to await high-quality clinical studies first. There are several good reasons for limiting opioid use and volatile anaesthetic concentrations in our clinical practice. But at this time, preventing cancer recurrence is not among them. None declared." @default.
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• W2118582478 title "Time to dial down the vaporizer?" @default.
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