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      Pancreatic Cancer Cachexia: The Role of Nutritional Interventions

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          Pancreatic cancer is a cancer with one of the highest mortality rates and many pancreatic cancer patients present with cachexia at diagnosis. The definition of cancer cachexia is not consistently applied in the clinic or across studies. In general, it is “defined as a multifactorial syndrome characterised 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.” Many regard cancer cachexia as being resistant to dietary interventions. Cachexia is associated with a negative impact on survival and quality of life. In this article, we outline some of the mechanisms of pancreatic cancer cachexia and discuss nutritional interventions to support the management of pancreatic cancer cachexia. Cachexia is driven by a combination of reduced appetite leading to reduced calorie intake, increased metabolism, and systemic inflammation driven by a combination of host cytokines and tumour derived factors. The ketogenic diet showed promising results, but these are yet to be confirmed in human clinical trials over the long-term. L-carnitine supplementation showed improved quality of life and an increase in lean body mass. As a first step towards preventing and managing pancreatic cancer cachexia, nutritional support should be provided through counselling and the provision of oral nutritional supplements to prevent and minimise loss of lean body mass.

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          Cancer cachexia: mediators, signaling, and metabolic pathways.

          Cancer cachexia is characterized by a significant reduction in body weight resulting predominantly from loss of adipose tissue and skeletal muscle. Cachexia causes reduced cancer treatment tolerance and reduced quality and length of life, and remains an unmet medical need. Therapeutic progress has been impeded, in part, by the marked heterogeneity of mediators, signaling, and metabolic pathways both within and between model systems and the clinical syndrome. Recent progress in understanding conserved, molecular mechanisms of skeletal muscle atrophy/hypertrophy has provided a downstream platform for circumventing the variations and redundancy in upstream mediators and may ultimately translate into new targeted therapies. Copyright © 2012 Elsevier Inc. All rights reserved.
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            Definition of cancer cachexia: effect of weight loss, reduced food intake, and systemic inflammation on functional status and prognosis.

            Cancer cachexia is a multifactorial syndrome that is poorly defined. Our objective was to evaluate whether a 3-factor profile incorporating weight loss (> or = 10%), low food intake ( or = 10 mg/L) might relate better to the adverse functional aspects of cachexia and to a patient's overall prognosis than will weight loss alone. One hundred seventy weight-losing (> or = 5%) patients with advanced pancreatic cancer were screened for nutritional status, functional status, performance score, health status, and quality of life. Patients were followed for a minimum of 6 mo, and survival was noted. Patients were characterized by using the individual factors, > or = 2 factors, or all 3 factors. Weight loss alone did not define a population that differed in functional aspects of self-reported quality of life or health status and differed only in objective factors of physical function. The 3-factor profile identified both reduced subjective and objective function. In the overall population, the 3 factors, > or = 2 factors, and individual profile factors (except weight loss) all carried adverse prognostic significance (P < 0.01). Subgroup analysis showed that the 3-factor profile carried adverse prognostic significance in localized (hazard ratio: 4.9; P < 0.001) but not in metastatic disease. Weight loss alone does not identify the full effect of cachexia on physical function and is not a prognostic variable. The 3-factor profile (weight loss, reduced food intake, and systemic inflammation) identifies patients with both adverse function and prognosis. Shortened survival applies particularly to cachectic patients with localized disease, thereby reinforcing the need for early intervention.
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              Risks and benefits of omega 3 fats for mortality, cardiovascular disease, and cancer: systematic review.

              To review systematically the evidence for an effect of long chain and shorter chain omega 3 fatty acids on total mortality, cardiovascular events, and cancer. Electronic databases searched to February 2002; authors contacted and bibliographies of randomised controlled trials (RCTs) checked to locate studies. Review of RCTs of omega 3 intake for (3) 6 months in adults (with or without risk factors for cardiovascular disease) with data on a relevant outcome. Cohort studies that estimated omega 3 intake and related this to clinical outcome during at least 6 months were also included. Application of inclusion criteria, data extraction, and quality assessments were performed independently in duplicate. Of 15,159 titles and abstracts assessed, 48 RCTs (36,913 participants) and 41 cohort studies were analysed. The trial results were inconsistent. The pooled estimate showed no strong evidence of reduced risk of total mortality (relative risk 0.87, 95% confidence interval 0.73 to 1.03) or combined cardiovascular events (0.95, 0.82 to 1.12) in participants taking additional omega 3 fats. The few studies at low risk of bias were more consistent, but they showed no effect of omega 3 on total mortality (0.98, 0.70 to 1.36) or cardiovascular events (1.09, 0.87 to 1.37). When data from the subgroup of studies of long chain omega 3 fats were analysed separately, total mortality (0.86, 0.70 to 1.04; 138 events) and cardiovascular events (0.93, 0.79 to 1.11) were not clearly reduced. Neither RCTs nor cohort studies suggested increased risk of cancer with a higher intake of omega 3 (trials: 1.07, 0.88 to 1.30; cohort studies: 1.02, 0.87 to 1.19), but clinically important harm could not be excluded. Long chain and shorter chain omega 3 fats do not have a clear effect on total mortality, combined cardiovascular events, or cancer.

                Author and article information

                Healthcare (Basel)
                Healthcare (Basel)
                09 July 2019
                September 2019
                : 7
                : 3
                [1 ]School of Medical Sciences, Faculty of Medical and Health Sciences, University of Auckland, Auckland 1023, New Zealand
                [2 ]Department of Nutrition, School of Medical Sciences, Faculty of Medical and Health Sciences, University of Auckland, Auckland 1023, New Zealand
                [3 ]Auckland Cancer Society Research Centre, School of Medical Sciences, Faculty of Medical and Health Sciences, University of Auckland, Auckland 1023, New Zealand
                Author notes
                © 2019 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).


                mechanisms, nutrition, pancreatic cancer, cachexia


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