Cachexia

Involuntary weight loss, a part of the cachexia syndrome, is a debilitating co-morbidity of cancer and currently has no treatment options. Results from a recent clinical trial at our institution showed that biliary tract cancer patients treated with a MEK inhibitor exhibited poor tumor responses, but surprisingly gained weight and increased their skeletal muscle mass. This implied that MEK inhibition might be anti-cachectic. To test this potential effect of MEK inhibition, we utilized the established Colon-26 model of cancer cachexia and the MEK½ inhibitor MEK162. Results showed that MEK inhibition effectively prevented muscle wasting. Importantly, MEK162 retained its ability to spare muscle loss even in mice bearing a Colon-26 clone resistant to the MEK inhibitor, demonstrating that the effects of blocking MEK is at least in part independent of the tumor. Because single agent MEK inhibitors have been limited as a front-line targeted therapy due to compensatory activation of other o...

Cancer anorexia-cachexia syndrome (CACS) is a devastating and debilitating aspect at any stage of malignancy. It presents primarily as anorexia, weight loss and muscle wasting secondary to inadequate oral intake and metabolic changes. This syndrome is highly prevalent among cancer patients, has a large impact on morbidity and mortality, and impinges on patient quality of life. The pathogenic mechanisms of CACS are multifactorial. It is suggested to be the result of tumor-host interactions and cytokines have a siginificant role. Diagnosis of cancer cachexia is complex and multifaceted and requires meticulous clinical examination of the patient. The challenge for clinicians is to know how best to manage the symptoms of weight loss and anorexia for optimal patient outcome. This article outlines the diagnosis of cancer cachexia, reviews its impact on patient quality of life and survival, and updates the reader on potential therapies that may suppress it.

Official post-mortem inspection records of poultry in 11 industrial poultry abattoirs in the Fars province, southern Iran, between 20 March 2002 and 19 March 2006 were used to investigate the character and prevalence of poultry loss caused by disease and pathological changes in the province. Linear regression analysis for study of time trend and chi2-test for investigation of seasonal pattern were used as statistical methods. In the study period, 130,967,021 birds were slaughtered. As a result of official veterinary inspection, 959,416 (0.73%) birds were condemned. The condemnation risk was calculated for each quarter in a year. Cachexia and septicemia were the most common reasons for rejection of carcasses and were responsible for 62% of the total condemnations. The condemnation risk due to septicemia increased over the study period from 0.14 to 0.22%. The rejection risk due to overscalding declined over the study period from 0.07 to 0.01%. No trends in time were observed for the o...

To develop a framework for the definition and classification of cancer cachexia a panel of experts participated in a formal consensus process, including focus groups and two Delphi rounds. Cancer cachexia was defined as a multifactorial syndrome defined by an ongoing loss of skeletal muscle mass (with or without loss of fat mass) that cannot be fully reversed by conventional nutritional support and leads to progressive functional impairment. Its pathophysiology is characterised by a negative protein and energy balance driven by a variable combination of reduced food intake and abnormal metabolism. The agreed diagnostic criterion for cachexia was weight loss greater than 5%, or weight loss greater than 2% in individuals already showing depletion according to current bodyweight and height (body-mass index [BMI] <20 kg/m(2)) or skeletal muscle mass (sarcopenia). An agreement was made that the cachexia syndrome can develop progressively through various stages--precachexia to cachexia...

Protein-energy malnutrition (PEM) is common in connection with chronic disease and is associated with increased morbidity and mortality. Because the risk of PEM is related to the degree of illness, the causal connections between malnutrition and a poorer prognosis are complex. It cannot automatically be inferred that nutritional support will improve the clinical course of patients with wasting disorders. We reviewed studies of the treatment of PEM in cases of chronic obstructive pulmonary disease, chronic heart failure, stroke, dementia, rehabilitation after hip fracture, chronic renal failure, rheumatoid arthritis, and multiple disorders in the elderly. Several methodologic problems are associated with nutrition treatment studies in chronically ill patients. These problems include no generally accepted definition of PEM, uncertain patient compliance with supplementation, and a wide range of outcome variables. Avail-able treatment studies indicate that dietary supplements, either al...

As previously suggested, it may be feasible to impede tumorevoked angiogenesis with a nutraceutical program composed of glycine, fish oil, epigallocatechin-3-gallate, selenium, and silymarin, complemented by a low-fat vegan diet, exercise training, and, if feasible, a salicylate and the drug tetrathiomolybdate. It is now proposed that the scope of this program be expanded to address additional common needs of cancer patients: blocking the process of metastasis; boosting the cytotoxic capacity of innate immune defenses (natural killer [NK] cells); preventing cachexia, thromboembolism, and tumor-induced osteolysis; and maintaining optimal micronutrient status. Modified citrus pectin, a galectin-3 antagonist, has impressive antimetastatic potential. Mushroombeta-glucans and probiotic lactobacilli can amplify NK activity via stimulatory effects on macrophages. Selenium, beta-carotene, and glutamine can also increase the number and/or cytotoxic activity of NK cells. Cachectic loss of muscle mass can be opposed by fish oil, glutamine, and beta-hydroxy-beta-methylbutyrate. Fish oil, policosanol, and vitamin D may have potential for control of osteolysis. High-dose aspirin or salicylates, by preventing NF-B activation, can be expected to aid prevention of metastasis and cachexia while down-regulating osteolysis, but their impacts on innate immune defenses will not be entirely favorable. A nutritional insurance formula crafted for the special needs of cancer patients can be included in this regimen. To minimize patient inconvenience, this complex core nutraceutical program could be configured as an oil product, a powder, and a capsule product, with the nutritional insurance formula provided in tablets. It would be of interest to test this program in nude mouse xenograft models.

To develop a framework for the definition and classification of cancer cachexia a panel of experts participated in a formal consensus process, including focus groups and two Delphi rounds. Cancer cachexia was defined as a multifactorial syndrome defined by an ongoing loss of skeletal muscle mass (with or without loss of fat mass) that cannot be fully reversed by conventional nutritional support and leads to progressive functional impairment. Its pathophysiology is characterised by a negative protein and energy balance driven by a variable combination of reduced food intake and abnormal metabolism. The agreed diagnostic criterion for cachexia was weight loss greater than 5%, or weight loss greater than 2% in individuals already showing depletion according to current bodyweight and height (body-mass index [BMI] <20 kg/m(2)) or skeletal muscle mass (sarcopenia). An agreement was made that the cachexia syndrome can develop progressively through various stages--precachexia to cachexia...

The purpose of this study was to test the validity of the Head and Neck Patient Symptom Checklist (HNSC). Three hundred and sixty-eight treatment-naive individuals with head and neck cancer prospectively completed the HNSC and the Patient-Generated Symptom Global Assessment (PG-SGA). The predictive validity was determined by comparing the HNSC symptoms interference scores to the PG-SGA scores. Multivariate logistic regression was used to determine the HNSC symptoms scores associated with reduced dietary intake, ≥ 5 % weight loss over 6 months, and reduced functional performance (FP). HNSC sensitivity (79-98 %), specificity (99-100 %), positive predictive value (92-100 %), and negative predictive value (94-100 %) were excellent, and the Cronbach's alpha coefficient was 0.92. The multivariate logistic regression showed that advanced tumor stage, pain, loss of appetite (LOA), and difficulty swallowing significantly predicted dietary intake. Advanced tumor stage, LOA, and difficulty swallowing were also significant predictors of ≥ 5 % weight loss over 6 months. LOA, difficulty swallowing, feeling full, and lack of energy were significant predictors of reduced FP. The HNSC appears to be a valid tool for determining symptoms interfering with dietary intake of head and neck cancer (HNC) patients. This instrument may aid in early identification of symptoms that place HNC patients at risk for reductions in dietary intake, weight, and functional performance.

Cachexia is defined as an unintended loss of stable weight exceeding 10%. Patients with advanced cachexia express anorexia, early satiety, severe weight loss, weakness, anemia, and edema. Anorexia represents the result of a failure of the usual appetite signals whereas cachexia is the debilitating state of involuntary weight loss. This syndrome, referred to as the cancer anorexia-cachexia syndrome, (CACS) and usually consists of a combination of anorexia, tissue wasting, malnutrition, weight loss and loss of compensatory increase in feeding. CACS represents the result of a complex interaction between cancer growth and host response and is associated with a poor response to chemotherapy and with an increase in drug-related toxicity. In advanced cachexia (mostly in metastatic cancer and terminally disease) any interventions with nutritional suplements are ineffective. Therefore, nutritional support in the reversion of tumor cachexia and in the importance of maintaining patient weight,...

Overweight and obesity adversely affect cardiovascular (CV) risk factors and CV structure and function, and lead to a marked increase in the risk of developing heart failure (HF). Despite this, an obesity paradox exists, wherein those who are overweight and obese with HF have a better prognosis than their leaner counterparts, and the underweight, frail, and cachectic have a particularly poor prognosis. In light of this, the potential benefits of exercise training and efforts to improve cardiorespiratory fitness, as well as the potential for weight reduction, especially in severely obese patients with HF, are discussed.

Cachexia is frequently described in patients with pancreatic ductal adenocarcinoma (PDAC) and is associated with reduced survival and quality of life. Unfortunately, the therapeutic options of this multi-factorial and complex syndrome are limited. This is due to the fact that, despite extensive preclinical and clinical research, the underlying pathological mechanisms leading to PDAC-associated cachexia are still not fully understood. Furthermore, there is still a lack of consensus on the definition of cachexia, which complicates the standardization of diagnosis and treatment as well as the analysis of the current literature. In order to provide an efficient therapy for cachexia, an early and reliable diagnosis and consistent monitoring is required, which can be challenging especially in obese patients. Although many substances have been tested in clinical and preclinical settings, so far none of them have been proven to have a long-term effect in ameliorating cancer-associated cache...

Megestrol acetate (MA) is a steroid origin medicine often used for control of cachexia in oncologic palliative care. Thrombosis is a common problem in oncology patients. One question is whether MA can cause thrombosis. This retrospective, registry-based analysis was therefore conducted to assess thrombotic processes in oncology patients using MA concurrent with chemotherapy. Data on oncology patients at the metastatic stage using MA were obtained from the archives of our center. Outcomes of patients were evaluated for thromboembolic events (VTEs) during treatment. Ninety-seven oncology patients with a median age of 62 (33-84) years were included. During the median follow-up of 17 months, 58 (59.8%) died leaving 39 (31.2%) still alive. Median overall survival (OS) was 19 months (6-180). Mean time of MA use was 8.69 months(±3.53), with a median dose of 160mg (range 160-480mg). Eleven VTEs were detected after MA use, 4 of these in pancreatic cancer cases. The patients with thrombosis n...

Introduction  Pancreatic cancer is the fourth leading cause of cancer-related death in Western countries with a poor prognosis (5-year survival rates, 25% in patients after tumor resection with adjuvant treatment; overall, the 5-year survival rate is about 4%; Jemal et al., CA Cancer J Clin, 55:10–30, 2005). Many patients develop a cachectic status during the progression of the disease, and this