What We Have Learned about Cachexia in Gastrointestinal Cancer

It is appreciated widely by clinicians that significant malnutrition accompanies malignant processes in approximately 50% of patients and eventually leads to severe wasting which accounts for approximately 30% of cancer-related deaths overall, 30–50% of deaths in patients with gastrointestinal tract cancers, and up to 80% of deaths in patients with advanced pancreatic cancer. The body wasting known as cancer cachexia is a complex syndrome characterized by progressive tissue depletion and decreased nutrient intake that is manifested clinically as inexplicable, recalcitrant anorexia and inexorable host weight loss. Decreased nutritional intake, increased metabolic expenditure and dysfunctional metabolic processes, including hormonal and cytokine-related abnormalities, all appear to play roles in the development of cancer cachexia. Although this condition of advanced protein-calorie malnutrition, sometimes described as the cancer anorexia-cachexia syndrome, is not entirely understood, it appears to be multifactorial, is a major cause of morbidity and mortality in cancer patients, and ultimately leads to death. Therapeutic interventions have met with little success, and, regardless of tremendous efforts throughout the decades, the exact nature of the mediators responsible for cancer cachexia remain elusive. The pathogenesis of cancer cachexia appears to be related to proinflammatory cytokines, alterations in the neuroendocrine axis and tumor-derived catabolic factors. Despite trials of conventional and/or aggressive nutritional support by a myriad of feeding techniques, patients with cancer cachexia have failed to gain consistent significant benefits in terms of weight gain, functional ability, quality of life or survival. Additionally, attempts to ameliorate the abnormal clinical and metabolic features of cancer cachexia with a variety of pharmacologic agents have met with only limited success. Either until cancer of the gastrointestinal tract can be cured or until it is possible to identify the exact causes and mechanisms of the cancer cachexia syndrome, the most realistic and practical options currently are directed toward minimizing adverse gastrointestinal side effects or complications of the malignant process and/or therapy, as well as increasing appetite, food intake and nutrient utilization in an effort to enhance quality of life and improve survival.