Effect of Anesthesia and Other Perioperative Techniques on Cancer Recurrence and Metastases

Abstract

SUMMARY S urgical excision is frequently an essential component of cancer management and it offers the best opportunity for a good prognosis in patients with solid tumors. However, it is known that surgical excision of the tumor can inadvertently facilitate the metastatic process. Metastatic disease is the most important cause of cancer-related death in these patients. The likelihood of tumor metastases depends on the balance between the metastatic potential of the tumor and the anti-metastatic host defenses, of which cell-mediated immunity, and natural killer cell function in particular, is a critical component. Surgery itself and the associated neuroendocrine stress response have a negative effect on the immune system due to depressed cell-mediated immunity. Even after complete excision of the tumor, circulating tumor cells released during the surgical procedure may eventually lead to recurrence or metastases as they escape the immune surveillance. It is increasingly recognized that anesthetic technique and other perioperative factors have the potential to effect long-term outcome after cancer surgery. Surgery can inhibit important host defenses and promote the development of metastases. Anesthetic technique and drug choice can interact with the cellular immune system and effect long-term outcome. Blood transfusion, pain, stress, and hypothermia are other potentially important perioperative factors that should be considered. Various factors that anesthesiologists select or manage during perioperative periods worsen or improve the immune systems of cancer patients and affect tumor metastases. Anesthesia impairs numerous immune functions, including those of neutrophils, macrophages, dendritic cells, T-cell, and natural killer (NK) cells. Induction agents (ketamine, thiopentone) as well as inhalation agents (halothane) have been shown to depress NK cell activity in animal studies. Upregulation of hypoxia-inducible-factors (HIF) in tumor cells by volatile anesthetics may contribute to a tumor's recurrence by stimulating cytoprotective or protumorigenic behavior in residual cells. Propofol may not contribute to the depression of immune function according to current available evidence. Propofol also does not upregulate synthesis of HIF. Amide local anesthetics have shown in vitro studies to have cytotoxic activity, which could prove to be beneficial in preventing cancer recurrence. Opioid analgesics inhibit both cellular and humoral immune function in humans, increase angiogenesis, and promote breast tumor growth in rodents. Opioids interfere with immune function by depressing NK cell activity. However, opioids may reduce the stress response to pain and offer some benefit. Regional anesthesia has been found to be associated with favorable prognosis in patients undergoing oncosurgery. By aborting surgery mediated neuroendocrine stress response and preserving the immune function, regional anesthesia alone or when combined with general anesthesia has protective effect in curbing postsurgical tumor recrudesce.