Cancer cachexia may be an immunologic phenomenon related to increased cytokine production that occurs in response to the tumor itself or to the stress of surgery, John M. Daly, MD, said at the Society of Surgical Oncology's Annual Cancer Symposium. As such, the routine administration of preoperative total parenteral nutrition (TPN) may not be a useful strategy for all types of cancer.
It is unlikely that cancer cachexia is due to a nutritional deficit alone, since administration of proper nutrition does not, by itself, abrogate the symptoms, said Dr. Daly, Lewis Arterbury Stimson Professor and Chairman, Department of Surgery, Cornell University Medical College, and Surgeon-in-Chief, The New York Hospital.
Additionally, malnutrition causes immunologic changes that resemble those in a cachectic cancer patient, Dr. Daly said in the Society's John Wayne Clinical Research Lecture. For example, a decreased and abnormal in vitro cellular response of many immune cells, such as neutrophils, natural killer (NK) cells, and lymphocytes, can be observed in both malnourished patients and those with cancer cachexia.
Monoclonal antibodies to immunologic cytokines such as tumor necrosis factor (TNF) or gamma-interferon have been shown to improve cachetic symptoms in animal experiments, thus providing support for an immunologic role in cancer-induced malnutrition, he said.
Dr. Daly questioned the routine use of preoperative TPN in the cancer patient, because of its cost, lack of established efficacy, and associated minor infectious
the routine use of preoperative TPN in the cancer patient, because of its cost, lack of established efficacy, and associated minor infectious complications. He suspects that these complications may result from the immunologic effects of TPN, which has been shown to decrease immune function in rats, down-regulating macrophage and splenocyte cell function.
Benefits of Supplemented TPN
However, when TPN is supplemented with certain amino acids, such as glutamine dipeptide, a clear benefit has been shown in bone marrow transplant patients in terms of decreased infections and shorter hospital stays, Dr. Daly said.
These supplements may serve as a form of "immuno-nutrition," acting on the body to increase the immune response, thus decreasing infections and improving wound healing, he said. The amino acid arginine, for example, has been shown to increase T-lymphocyte, macrophage, and NK cell activation; cytokine production; and the delayed-type hypersensitivity response.
Dr. Daly said that adding amino acids or certain fatty acids to TPN may give patients a better postoperative outcome. For example, esophageal carcinoma patients undergoing esophagectomy were improved postoperatively when given enteral nutrition supplemented with arginine and omega 3-fatty acids (eicosapentanoic acid).
Such evidence suggests a model in which cancer-related malnutrition leads to immune suppression that could result in infection and metastases.
Supplemented enteral nutrition may have a role in improving the immune response under such conditions, Dr. Daly said. However, for many cancers, preoperative TPN does not seem to be indicated, considering the risk of complications. He believes that its routine use should be avoided, and preoperative supplemented TPN should be used only in patients with severe malnutrition or in those undergoing bone marrow transplantation.