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April 13, 1999

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Stress and Surgery May Increase Development of Cancerous Tumors

Stress and surgery may increase the growth of cancerous tumors by suppressing natural killer cell activity, says a Johns Hopkins nurse researcher.

Malignancies and viral infection are in part controlled by the immune system's natural killer (NK) cells, a sub-population of white blood cells that seek out and kill certain tumor and virally infected cells. In a study using animal models, natural killer cell activity was suppressed by physical stress or surgery, resulting in a significant increase in tumor development. These findings suggest that protective measures should be considered to prevent metastasis for patients undergoing surgery to remove a cancerous tumor, according to Gayle Page, D.N.Sc., R.N., associate professor and Independence Foundation chair at the Johns Hopkins School of Nursing.

"Human studies have already found a connection between the level of NK activity and susceptibility to several different types of cancer," says Page, an author of the study. "We sought to determine the importance of stress-induced suppression of NK activity and thus learn the effects of stress and surgery on tumor development. Many patients undergo surgery to remove cancerous tumors that have the potential to spread. If our findings in rats can be generalized to such clinical settings, then these circumstances could increase tumor growth during or shortly after surgery."

The research was conducted at Ohio State University College of Nursing and the Department of Psychology at UCLA, where Page held previous positions, and at Tel Aviv University. Results of the study are published in the March issue of the International Journal of Cancer.

In laboratory studies, Page and her colleagues subjected rats to either abdominal surgery or physical stress, and then inoculated them with cancer cells. In the rats that had undergone surgery, the researchers observed a 200 to 500 percent increase in the incidence of lung tumor cells, an early indicator of metastasis, compared with rats that had not received surgery. The experiment also showed that stress increased lung tumor incidence and significantly increased the mortality in the animals inoculated with cancer cells.

"Our results show that, under specific circumstances, resistance to tumor development is compromised by physical stress and surgical intervention," says Page. "Because surgical procedures are life-saving and cannot be withheld, protective measures should be considered that will prevent suppression of the natural killer cell activity and additional tumor development. Researchers do not yet know how to prevent surgery-induced immune suppression, but early animal studies have shown increased use of analgesia reduces the risk."

The study was funded by the National Institutes of Health, and the Chief Scientist of the Israeli Ministry of Health. Lead author was Shamgar Ben-Eliyahu, Ph.D., and other authors were Raz Yirmiya, Ph.D., and Guy Shakhar.


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