Cancers 2010, 2(4), 1929-1951; doi:10.3390/cancers2041929
Review

Surgery as a Double-Edged Sword: A Clinically Feasible Approach to Overcome the Metastasis-Promoting Effects of Surgery by Blunting Stress and Prostaglandin Responses

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Received: 13 October 2010; in revised form: 14 November 2010 / Accepted: 23 November 2010 / Published: 24 November 2010
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract: Surgery remains an essential therapeutic approach for most solid malignancies, including breast cancer. However, surgery also constitutes a risk factor for promotion of pre-existing micrometastases and the initiation of new metastases through several mechanisms, including the release of prostaglandins and stress hormones (e.g., catecholamines and glucocorticoids). However, the perioperative period also presents an opportunity for cell mediated immunity (CMI) and other mechanisms to eradicate or control minimal residual disease, provided that the deleterious effects of surgery are minimized. Here, we discuss the key role of endogenous stress hormones and prostaglandins in promoting the metastatic process through their direct impact on malignant cells, and through their deleterious impact on anti-cancer CMI. We further discuss the effects of anesthetic techniques, the extent of surgery, pain alleviation, and timing within the menstrual cycle with respect to their impact on tumor recurrence and physiological stress responses. Last, we suggest an attractive perioperative drug regimen, based on a combination of a cyclooxygenase (COX)-2 inhibitor and a β-adrenergic blocker, which we found effective in attenuating immune suppression and the metastasis-promoting effects of surgery in several tumor models. This regimen is clinically applicable, and could potentially promote disease free survival in patients operated for breast and other types of cancer.
Keywords: surgery; perioperative period; immunosuppression; prophylactic interventions; natural killer cells; stress; breast cancer
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MDPI and ACS Style

Benish, M.; Ben-Eliyahu, S. Surgery as a Double-Edged Sword: A Clinically Feasible Approach to Overcome the Metastasis-Promoting Effects of Surgery by Blunting Stress and Prostaglandin Responses. Cancers 2010, 2, 1929-1951.

AMA Style

Benish M, Ben-Eliyahu S. Surgery as a Double-Edged Sword: A Clinically Feasible Approach to Overcome the Metastasis-Promoting Effects of Surgery by Blunting Stress and Prostaglandin Responses. Cancers. 2010; 2(4):1929-1951.

Chicago/Turabian Style

Benish, Marganit; Ben-Eliyahu, Shamgar. 2010. "Surgery as a Double-Edged Sword: A Clinically Feasible Approach to Overcome the Metastasis-Promoting Effects of Surgery by Blunting Stress and Prostaglandin Responses." Cancers 2, no. 4: 1929-1951.

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