Is There a Direct Effect?

T HERE has been increasing interest in the role of anesthetic drugs and opioids in cancer recurrence and metastasis. Epidemiologic studies in this area have suggested that patients who receive general anesthesia with opioids rather than local or regional anesthetics have a greater rate of cancer recurrence. Several retrospective studies have shown a reduced incidence of cancer recurrence after regional anesthesia (epidural, intrathecal, paravertebral) and reduced doses of opioids after surgery for breast, prostate, and colon cancer or melanoma, although other groups have reported less robust association. Retrospective studies of anesthetic choice and disease-free survival studies are subject to confounding factors; however, prospective trials are under way. Assuming the retrospective epidemiologic data demonstrating an effect of anesthetic technique on cancer recurrence are substantiated, it would be important to determine the mechanisms involved. The epidemiologic research has focused largely on potential beneficial effects of regional anesthetics, yet the differences in cancer recurrence rate may be the result of direct or indirect effects on tumor cell growth and metastasis by anesthetic or opioids. Direct effects include stimulating tumor cell proliferation and invasion and inhibiting apoptosis; indirect effects include immunosuppression. The purpose of this review is to assess the possible role of opioids in tumor progression, with a focus on the -opioid receptor (MOR) and its direct influence on cancer progression.