Metabolic changes in cancer cachexia — first of two parts

Abstract

Weight loss and malnutrition have long been associated with a poor clinical outcome after surgery (1). Anorexia, muscle wasting and progressive depletion of adipose tissue have often been described in cancer patients and the clinical syndrome associated with these symptoms is referred to as cancer cachexia (2, 3). The condition of the cachectic cancer patient differs from simple malnutrition due to fasting or starvation because host intermediary metabolism (carbohydrate, lipid and protein metabolism) is abnormal limiting the success of nutritional therapy (3, 4). Reports on the incidence of cancer cachexia at the time of presentation in a clinical setting vary between 3% and more than 80% (5-10). The variation is in part caused by differences in cancer populations studied. In addition, there appears to be a lack of convenient indicators to assess nutritional depletion. Most surveys have concentrated on weight loss, lean body mass, depletion of fat mass or serum protein levels (1, 8, 11). These parameters, however, are not only a reflection of the nutritional status but are also influenced by the disease state of the patient (12, 13). To improve the nutritional assessment of patients, several nutritional indices were introduced to better identify patients at risk for nutrition related complications and to assess the efficiency of nutritional interventions (8, 11, 12, 14, 15). Most of these indices, however, remain more dependent on the disease status than on nutritional status. In our hospital, approximately 60% of the patients admitted to the surgical ward for gastrointestinal cancer are nutritionally depleted. In a multivariate analysis blood loss and age, but not nutritional depletion, were associated with the development of postoperative complications (12). Nutritional depletion was only associated with the severity of a complication once a complication was present. This emphasizes that impact of the nutritional status compared to other factors only mildly affects the risk of complications and that a nutritional intervention can only have limited impact. Nutritional support to cancer patients was greatly improved in the 1970s with the introduction of total parenteral nutrition (TPN). Although it was first thought that TPN could completely reverse protein catabolism and improve clinical outcome of cachectic cancer patients (16), this was not reaffirmed in later studies (17, 18). This can be attributed to the abnormal metabolic response to nutrients by cancer patients and the inability to reverse metabolic defects by artificial nutrition. In an elegant study Shaw et al showed with 14C[urea] that whole body protein anabolism, which can be achieved by giving parenteral nutrition to unstressed depleted patients with benign disease, cannot be achieved in cancer patients, whether depleted or not (13, 19). The ongoing catabolism could only be blunted with parenteral nutrition. To further improve the efficacy of nutritional support in cancer patients, fundamental research has tried to elucidate the underlying changes in intermediary metabolism to appropriately counter these changes and improve clinical outcome (17, 18). Most of these findings have been demonstrated to occur before any signs of weight loss and anorexia are present, suggesting that these metabolic changes are cause rather than consequence of cancer cachexia (20-26). This review summarizes the abnormalities in carbohydrate, lipid, protein and amino acid metabolism observed in cancer.