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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.
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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.
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Opioid drugs, specifically strong μ-agonists, have
Veterinary Clinics of North America: Small Animal Practice
Immunomodulatory Effects of Surgery, Pain, and Opioids in Cancer Patients
Section snippets
Key points
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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The authors have no conflicts of interest to report.