Cancer prognosis: can anesthesia play a role?

501 September 2013 S URGERY remains a primary treatment for cancer. It is therefore important to know whether any perioperative factors, including anesthetic(s), can positively or negatively affect the prognosis of cancer. In this issue of AnEsthEsIoloGY, Benzonana et al.1 have reported the effects of anesthetic isoflurane on the growth and migration (malignant potential) of renal cancer cells. The debate on whether anesthetics and other associated perioperative events can influence the long-term prognosis of cancer patients who undergo surgery has been steadily gaining momentum in recent years. several retrospective studies have suggested that resection of cancers by surgeries with regional anesthesia could be associated with better outcomes as compared those with general anesthesia in several types of cancer, including breast, colon, prostate, and ovary.2–5 In particular, lin et al.5 have shown that patients who had radical prostatectomy with epidural anesthesia have a 57% lower recurrence rate as compared with those who had the radical prostatectomy with general anesthesia. however, contradictory clinical reports also exist, and it is therefore urgent to perform more clinical studies to determine the role of anesthesia in the outcomes and prognosis of cancer. An early study has shown that general anesthetics such as halothane and nitrous oxide might accelerate postoperative metastasis (even to the organs in which they are not usually found) in lung cancer and melanoma in murine models.6 A recent study has suggested that volatile anesthetics could affect gene expression in human breast and brain tumor cell lines.7 however, the further characterization of the effects of anesthetics on cancer growth and metastasis and the underlying mechanisms remain to be determined. specifically, there has been a need to more clearly define the impact of the various anesthetic and analgesic agents on the risk of developing postoperative tumor recurrence or metastases, and there have been calls for researchers to offer greater clues as to the likely etiology of such findings. to date, those clues are largely centered around how anesthetics modulate various arms of the immune system, the neuroendocrine system, and the stress response that inevitably accompanies surgery. Benzonana et al. offer a fresh perspective in which they report that isoflurane, a commonly used inhalation anesthetic, can act on cancer cells and the signaling pathways directly in a way that enhances the malignant and metastatic potential of the cancer cells. An article based on these findings has been published in this issue of AnEsthEsIoloGY. They focused on hypoxia-inducible factors (hIFs)— ubiquitously expressed transcription factors that regulate cellular oxygen homeostasis and govern the expression of hundreds of genes that work together to ensure a cell’s survival and adaptation to its environment. such an integral role in the cell’s survival apparatus makes hIFs an attractive target for cancer cells to take advantage of; indeed high levels of hIFs are the feature of most solid cancers, and the Cancer Prognosis