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Characterized by weight loss, anorexia, muscle wasting and decreased survival.
It is a multifactorial syndrome with a weight loss of more than 5% during a six month period or weight loss of of more than 2% in patients with either BMI of less than 20 or sarcopemia.
A combination of weight loss, muscle and fat tissue loss, anorexia, hyperglycemia, hyperlipidemia and anemia.
In contrast to sarcopenia, it is not caused by aging itself, but is a result of metabolic alterations due to disease.
Etiology unclear and no effective treatment exists.
It is a common complication of cancer and is associated with an increased risk of death.
Patients with cachexia have reduce psychological, emotional, and social well-being related to their inadequate food intake, altered body image, and reduced physical function.
The level of growth differentiation factor 15 (GDF-15), which is a circulating cytokine, is elevated in cancer cachexia.
Refers to severe wasting of both fat and muscle mass and loss of weight, mediated by a systemic inflammatory process in the presence of a severe chronic illness.
Weight loss occurs over a short period of time, and there is failure of nutritional support, and the presence of abnormal biochemistry.
Caused by interaction of tumor and its proinflammatory and neurohormonal dysfunction.
Estimated that nearly 1/3 of cancer deaths can be attributed to cachexia, a wasting syndrome characterized by dramatic loss of skeletal muscle and often accompanied by significant weight loss.
Commonly occurs in many cancers, usually in the advanced stages of disease, and is most commonly seen in pancreatic and gastric cancer, as well as lung, esophageal, colorectal, and head and neck cancer.
About 1/2 of patients with cancer with experience cachexia at some phase in the therapy.
At the time of death it’s probably closer to 80% and 20 to 30% of patients die from the wasting syndrome only.
Factors that contribute to metabolic changes and protein degradation are proinflammatory cytokines, and in cancer patients, tumor metabolism.
Suspected that cytokines decrease the production and increased the degradation of myosin.
In combination of tumor necrosis factor-alpha and other cytokines trigger a selective reduction in myosin heavy chain expression.
No consistent correlation with this process and serum concentration of cytokines.
To improve appetite and weight gain trials of progesterone analog, or glucocorticoids offer the potential for limited benefits.
The hypothalamus balances orexigenic and anorexigenic neurocircuits which tailor nutrient influx during meals by balancing appetite and satiation, and the functions vested in the brainstem are considered to be alarm responses that swiftly halt food intake.
Some guidelines support the use of low-dose olanzapine to improve appetite and weight.
Cancer cachexia is defined by progressive weight loss in the presence of an underlying neoplastic disease which may culminate in muscle depletion and adipose tissue and ultimately death.
Cancer cachexia is triggered by neoplasm, but, in tumor induced immune activation, and targets of cancer therapies are also factors.
Severe nutrient deficiency is common in advanced cancer with a quarter of patients consuming less than 13 kcal per kilogram of weight per day-equivalent to hypocaloric diets described for intentional weight loss of approximately 2.5 kg over a period of 30 days in patients with obesity.
Growth differentiation factor (GDF-15) is a stress induced cytokine that binds to the glial derived neutrophilic factor family receptor alpha-like protein (GFRAL) in the hindbrain.
GDF-15 has emerged as the main modulator of anorexia and body weight regulation it is implicated in the pathogenesis of cachexia.
GDF-15 binds to its receptor expressed on neurons in the area, postrema and nucleus of the solitary tract of the brainstem, inducing, anorexigenic and adversive responses and nausea.
Elevated GDF 15 levels are associated with the loss of weight and skeletal muscle mass along with reduced strength and survival in patients with cancer.
GDF-15 is over expressed by many tumors and it is also induced by non-tumor tissues by cancer therapies, particularly cisplatinum.
Among patients with cancer cachexia and elevated GDF-15 levels the inhibition of GDF-15 with ponsegromab resulted in increased weight gain and overall activity level and reduced cachexia symptoms, confirming the role of GDF-15 as a driver of cancer cachexia (Groarke JD).