Immunomodulatory Effects of Surgery, Pain, and Opioids in Cancer Patients

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Key points

  • Surgical removal of a primary tumor can accelerate metastatic progression at distant sites through a complex interaction between the primary tumor, its microenvironment, circulating tumor cells, the immune system, and sites of metastasis.

  • Perioperative immunosuppression has been implicated as a key factor in surgery-associated accelerated tumor progression, and anesthetic/analgesic protocol may influence, in part, this phenomenon.

  • Opioid drugs, specifically strong μ-agonists, have

Surgery accelerates progression of metastatic disease

The hypothesis that cancer surgery accelerates tumor progression elsewhere in the body dates back to the turn of the twentieth century.1 Experimental evidence supporting this clinical observation soon followed using transplantable mouse tumor models. One such study, published in 1913, found that mice undergoing incomplete surgical removal of an inoculated tumor had a larger metastatic disease burden compared with nonoperated control mice.2 In these early experiments, sham surgeries were not

Anesthetic protocol influences progression-free survival—A role for opioids?

In people, and likely similarly in dogs, approximately 80% of patients undergo some form of anesthesia, whether for diagnostic or treatment purposes, during the course of their cancer treatment of solid tumors. Accumulating evidence suggests alterations in the immune system as a result of anesthesia contribute to cancer progression. Several studies, most retrospective in nature, have shown also that the degree at which these alterations effect cancer progression can be related to specific

Specific immunomodulatory and potentially cancer-promoting effects of opioids

Opioids are among the most effective and powerful analgesics available for treating pain. Opioids exert their canonical analgesic effects via binding to opioid receptors in the central nervous system. Opioid receptors are located throughout the body, however, which contributes to the numerous nonanalgesic effects of opioid administration. Of particular interest to cancer biology and tumor microenvironment, opioids interact with the endothelium, tumor cells, and inflammatory cells via opioid

Summary

Surgery, anesthesia, nociception, and opioid use alone or in combination cannot solely explain the phenomenon of postsurgery metastasis acceleration, and it cannot be over-emphasized that these processes are multifactorial and incompletely understood. As such, strong recommendations as to how clinicians should treat patients based on currently available evidence is not possible. Ultimately, clinicians should implement treatment decisions based on individual risk-benefit analyses and adjust

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References (42)

  • S. Benzekry et al.

    Mathematical modeling of tumor-tumor distant interactions supports a systemic control of tumor growth

    Cancer Res

    (2017)
  • Z.Y. Wang et al.

    Primary tumorectomy promotes angiogenesis and pulmonary metastasis in osteosarcoma-bearing nude mice

    Acta Cir Bras

    (2013)
  • M. Ikeda et al.

    Surgery for gastric cancer increases plasma levels of vascular endothelial growth factor and von Willebrand factor

    Gastric Cancer

    (2002)
  • A. Belizon et al.

    Major abdominal surgery increases plasma levels of vascular endothelial growth factor: open more so than minimally invasive methods

    Ann Surg

    (2006)
  • J.A. Dubowitz et al.

    Implicating anaesthesia and the perioperative period in cancer recurrence and metastasis

    Clin Exp Metastasis

    (2018)
  • T.J. Wigmore et al.

    Long-term survival for patients undergoing volatile versus IV anesthesia for cancer surgery: a retrospective analysis

    Anesthesiology

    (2016)
  • B. Schlagenhauff et al.

    Prognostic impact of the type of anaesthesia used during the excision of primary cutaneous melanoma

    Melanoma Res

    (2000)
  • A.K. Exadaktylos et al.

    Can anesthetic technique for primary breast cancer surgery affect recurrence or metastasis?

    Anesthesiology

    (2006)
  • J.G. Hiller et al.

    Perioperative epidural analgesia reduces cancer recurrence after gastro-oesophageal surgery

    Acta Anaesthesiol Scand

    (2014)
  • B.J. Ciepluch et al.

    Long-term postoperative effects of administration of allogeneic blood products in 104 dogs with hemangiosarcoma

    Vet Surg

    (2018)
  • T. Miyata et al.

    Influence of general anesthesia with isoflurane following propofol-induction on natural killer cell cytotoxic activities of peripheral blood lymphocytes in dogs

    J Vet Med Sci

    (2013)
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    The authors have no conflicts of interest to report.

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