Physiopathologie de la dénutrition chez le cancéreux

The clinical syndrome assiociated with anorexia, muscle wasting and depletion of fat stores is referred to as cancer cachexia. Several physiological derangements have been implicated as possible underlying mechanisms of anorexia, such as food aversions, dysphagia, mucositis, delayed digestion, intestinal atrophy, increased lactate levels and increased cerebral serotonin production. A number of circulating factors have been documented as causes of anorexia and metabolic disturbances of cachexia, but the exact mechanims of action and the respective responsability of cytokines, neuropeptide Y and other humoral mediators such as lipid mobilizing factors and proteoglycans remain unclear.Energy expenditure is usually elevated in cancer, but unchanged and hypometabolic responses have also been described. Carbohydtrate metabolism is characterized by increased glucose turnover, increased gluconeogenesis and insulin resistance. Depletion of fat stores with hyperlipidemia are common characteristics, but the contribution of decreased lipogenesishas been poorly investigated. Observed alterations in specific protein metabolism include increased protein turnover, decreased skeletal muscle protein synthesis, increased hepatic protein synthesis with repriorization of acute phase reactant poduction, host nitrogen depletion and inconsistent alterations in plasma aminoacid profile. The role of glutamine and arginine, both being considered as « coaditionnally essential » and as potential immunomodulators in this setting, is under unvestigation. To date, although some of the cachexia-related metabolic abnormalities have been elucidated, there have been little success related to therapeutic manipulations of these pathways: this raises caution against enthusiasm concerning novel and, hazardous approaches in the treatment of this syndrome.