To the Editor:—

An increase in the rate of development of tumor metastasis, controversially attributed to immune suppression related to various aspects of surgery and anesthesia, has been reported for years and is discussed in an article 1and commentary 2that appeared in the September 1999 issue of Anesthesiology. However, it is important to point out that facilitation of metastasis can occur independent of immune mechanisms. Indeed, metastasis can be stimulated by the removal of an angiogenesis inhibitor (such as angiostatin) along with the primary tumor (as reviewed in Cramer 3). (Angiostatin is a naturally occurring protein shown in animal experiments to strongly suppress metastasis. 4)

It seems imperative that continued research into the traditional areas of immune suppression/modulation must be coupled with more recent findings (e.g. , angiogenesis inhibitors) if we are to truly understand the pathobiology of perioperative metastasis. Such integrated research seems necessary if we are to devise effective clinical strategies to decrease the incidence of postoperative metastasis.

Ben-Eliyahu S, Shakhar G, Rosenne E, Levinson Y, Beilin B: Hypothermia in barbiturate-anesthetized rats suppress natural killer cell activity and compromises resistance to tumor metastasis. A nesthesiology 1999; 91:732–40
Klein HG: Immunomodulatory aspects of transfusion: A once and future risk? A nesthesiology 1999; 91:861–5
Cramer DA: Applied vascular biology: Can angiogenesis inhibitors help control malignant growth? Ann Intern Med 1998; 129:841–3
O’Reilly M, Holmgren L, Shing Y, Chen C, Rosenthal RA, et al: Angiostatin: A novel angiogenesis inhibitor that mediates the suppression of metastases by a Lewis lung carcinoma. Cell 1994; 79:315–28