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Originally published as JCO Early Release 10.1200/JCO.2009.23.7651 on August 3 2009 © 2009 American Society of Clinical Oncology.
Effects of Anesthetics on Cancer RecurrenceDepartment of Anesthesia and Critical Care, The University of Chicago, Chicago, IL
Medical Affairs, Progenics Pharmaceuticals, Tarrytown, NY To the Editor: We read with great interest the recent article by Weckermann et al1 on the perioperative activation of disseminated tumor cells in bone marrow of patients with prostate cancer. The authors postulate "unknown perioperatively acting triggers that stimulate outgrowth of DTCs" (disseminated tumor cells). Recent clinical and laboratory data suggest that anesthetic technique may play a role in tumor dissemination and recurrence. This issue has been highlighted in the anesthesia literature in a recent article of the Anesthesia Patient Safety Foundation Newsletter, which reviews the clinical and laboratory data for such an effect.2 In a retrospective study of prostate cancer,3 there was a significant difference in the rate of tumor recurrence contingent on the type of anesthesia used. A small retrospective study in breast cancer had similar findings.4 A large, multicenter, prospective, randomized trial investigating the influence of type of anesthesia on breast cancer recurrence is currently underway.5 In addition to the clinical studies, there is also an evolving basic science literature suggesting that opiates affect tumor growth. Both we6 and Gupta et al7 have shown that clinically relevant concentrations of opiates can cause endothelial cell proliferation and migration in vitro. The proangiogenic effect of mu opioid agonists seems to be the result of reciprocal transactivation of the vascular endothelial growth factor receptor. We have also demonstrated that mu opioids induce a defect in barrier function, potentially allowing penetration of tumor cells.8 The effects of mu agonists on both angiogenesis and barrier function are reversed by tertiary opiate antagonists or by methylnaltrexone, a peripherally acting mu opioid receptor antagonist approved in the United States to treat opioid-induced constipation in patients with advanced illness receiving palliative care when response to laxatives has not been sufficient.9,10 If these laboratory studies are confirmed clinically, then the selection of anesthetic technique used during the operative procedure and the possible use of peripheral mu opioid receptor antagonists in the perioperative period may be of potential importance. It would be particularly interesting if the authors were able to review the perioperative records of their patients to see which drugs were administered and what anesthetic techniques were used. We commend the authors for their diligent work and believe that their observations deserve additional investigation. AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST Although all authors completed the disclosure declaration, the following author(s) indicated a financial or other interest that is relevant to the subject matter under consideration in this article. Certain relationships marked with a "U" are those for which no compensation was received; those relationships marked with a "C" were compensated. For a detailed description of the disclosure categories, or for more information about ASCO's conflict of interest policy, please refer to the Author Disclosure Declaration and the Disclosures of Potential Conflicts of Interest section in Information for Contributors. Employment or Leadership Position: Robert J. Israel, Progenics Pharmaceuticals (C) Consultant or Advisory Role: Jonathan Moss, Progenics Pharmaceuticals (C) Stock Ownership: Jonathan Moss, Progenics Pharmaceuticals; Robert J. Israel, Progenics Pharmaceuticals Honoraria: Jonathan Moss, Progenics Pharmaceuticals Research Funding: None Expert Testimony: None Other Remuneration: Jonathan Moss, patent holder, methylnaltrexone REFERENCES
1. Weckermann D, Polzer B, Ragg T, et al: Perioperative activation of disseminated tumor cells in bone marrow of patients with prostate cancer. J Clin Oncol 27:1549–1556, 2009. 2. Durieux ME. Does anesthetic management affect cancer outcome? http://www.apsf.org/assets/Documents/winter2009.pdf. 3. Biki B, Mascha E, Moriarty DC, et al: Anesthetic technique for radical prostatectomy surgery affects cancer recurrence: A retrospective analysis. Anesthesiology 109:180–187, 2008.[CrossRef][Medline] 4. Exadaktylos AK, Bugy DJ, Moriarty DC, et al: Can anesthetic technique for primary breast cancer surgery affect recurrence or metastasis? Anesthesiology 105:660–664, 2006.[CrossRef][Medline] 5. Sessler DI, Ben-Eliyahu S, Mascha EJ, et al: Can regional analgesia reduce the risk of recurrence after breast cancer? Methodology of a multicenter randomized trial. Contemp Clin Trials 29:517–526, 2008.[CrossRef][Medline] 6. Gupta K, Kshirsagar S, Chang L, et al: Morphine stimulates angiogenesis by activating proangiogenic and survival-promoting signaling and promotes breast tumor growth. Cancer Res 62:4491–4498, 2002. 7. Singleton PA, Lingen MW, Fekete MJ, et al: Methylnaltrexone inhibits opiate and VEGF-induced angiogenesis: Role of receptor transactivation. Microvasc Res 72:3–11, 2006.[CrossRef][Medline] 8. Singleton PA, Moreno-Vinasco L, Sammani S, et al: Attenuation of vascular permeability by methylnaltrexone: Role of mOP-R and S1P3 transactivation. Am J Respir Cell Mol Biol 37:222–231, 2007. 9. Methylnaltrexone (Relistor) for opioid-induced constipation. Med Lett Drugs Ther 50:63–64, 2008.[Medline] 10. Moss J, Rosow CE: Development of peripheral opioid antagonists: New insights into opioid effects. Mayo Clin Proc 83:1116–1130, 2008.
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Copyright © 2009 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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