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1.
Ketogenic Diets in Pancreatic Cancer and Associated Cachexia: Cellular Mechanisms and Clinical Perspectives.
Cortez, NE, Mackenzie, GG
Nutrients. 2021;(9)
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive and extremely therapy-resistant cancer. It is estimated that up to 80% of PDAC patients present with cachexia, a multifactorial disorder characterized by the involuntary and ongoing wasting of skeletal muscle that affects therapeutic response and survival. During the last decade, there has been an increased interest in exploring dietary interventions to complement the treatment of PDAC and associated cachexia. Ketogenic diets (KDs) have gained attention for their anti-tumor potential. Characterized by a very low carbohydrate, moderate protein, and high fat composition, this diet mimics the metabolic changes that occur in fasting. Numerous studies report that a KD reduces tumor growth and can act as an adjuvant therapy in various cancers, including pancreatic cancer. However, research on the effect and mechanisms of action of KDs on PDAC-associated cachexia is limited. In this narrative review, we summarize the evidence of the impact of KDs in PDAC treatment and cachexia mitigation. Furthermore, we discuss key cellular mechanisms that explain KDs' potential anti-tumor and anti-cachexia effects, focusing primarily on reprogramming of cell metabolism, epigenome, and the gut microbiome. Finally, we provide a perspective on future research needed to advance KDs into clinical use.
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2.
Role of Cachexia and Fragility in the Patient Candidate for Cardiac Surgery.
Pisano, C, Polisano, D, Balistreri, CR, Altieri, C, Nardi, P, Bertoldo, F, Trombetti, D, Asta, L, Ferrante, MS, Buioni, D, et al
Nutrients. 2021;(2)
Abstract
Frailty is the major expression of accelerated aging and describes a decreased resistance to stressors, and consequently an increased vulnerability to additional diseases in elderly people. The vascular aging related to frail phenotype reflects the high susceptibility for cardiovascular diseases and negative postoperative outcomes after cardiac surgery. Sarcopenia can be considered a biological substrate of physical frailty. Malnutrition and physical inactivity play a key role in the pathogenesis of sarcopenia. We searched on Medline (PubMed) and Scopus for relevant literature published over the last 10 years and analyzed the strong correlation between frailty, sarcopenia and cardiovascular diseases in elderly patient. In our opinion, a right food intake and moderate intensity resistance exercise are mandatory in order to better prepare patients undergoing cardiac operation.
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3.
Nutrition and gastroenterological support in end of life care.
Schütte, K, Middelberg-Bisping, K, Schulz, C
Best practice & research. Clinical gastroenterology. 2020;:101692
Abstract
Malnutrition and the broad spectrum of cancer cachexia frequently occur in patients with malignant disease of all tumour stages and impact on survival and quality of life of patients. Structured screening for the risk of malnutrition with validated tools and nutritional assessment are the prerequisite for adequate nutritional support in cancer patients. In patients receiving tumour directed therapy, the patients diet should meet the requirements to give optimal support, while later on comfort feeding is part of symptom focused palliation. The basis of nutritional support in a malnourished patient is nutritional counselling, and nutritional support can be offered within a step-up approach meeting the patient's needs. A combination of nutritional support with interventions targeting metabolic changes and physical exercise is suggested to treat cancer cachexia.
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4.
Cancer Cachexia and Related Metabolic Dysfunction.
Fonseca, GWPD, Farkas, J, Dora, E, von Haehling, S, Lainscak, M
International journal of molecular sciences. 2020;(7)
Abstract
Cancer cachexia is a complex multifactorial syndrome marked by a continuous depletion of skeletal muscle mass associated, in some cases, with a reduction in fat mass. It is irreversible by nutritional support alone and affects up to 74% of patients with cancer-dependent on the underlying type of cancer-and is associated with physical function impairment, reduced response to cancer-related therapy, and higher mortality. Organs, like muscle, adipose tissue, and liver, play an important role in the progression of cancer cachexia by exacerbating the pro- and anti-inflammatory response initially activated by the tumor and the immune system of the host. Moreover, this metabolic dysfunction is produced by alterations in glucose, lipids, and protein metabolism that, when maintained chronically, may lead to the loss of skeletal muscle and adipose tissue. Although a couple of drugs have yielded positive results in increasing lean body mass with limited impact on physical function, a single therapy has not lead to effective treatment of this condition. Therefore, a multimodal intervention, including pharmacological agents, nutritional support, and physical exercise, may be a reasonable approach for future studies to better understand and prevent the wasting of body compartments in patients with cancer cachexia.
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5.
Dietary Amino Acids and Immunonutrition Supplementation in Cancer-Induced Skeletal Muscle Mass Depletion: A Mini-Review.
Soares, JDP, Howell, SL, Teixeira, FJ, Pimentel, GD
Current pharmaceutical design. 2020;(9):970-978
Abstract
Cancer patients display systemic inflammation, which leads to an increase in protein catabolism, thus promoting the release of free amino acids to further support metabolism and remodelling of muscle proteins. Inflammation associated with tumor growth leads to malnutrition, a factor that increases the risk of developing cachexia. With cancer-induced cachexia, nutritional interventions have gained traction as a preventative method to manage this condition. Currently, cancer consensus recommendations suggest a protein intake above 1.0 g/kg.day-1 up to 2.0 g/k.day-1 for cancer patients, although an ideal amount for some amino acids in isolation has yet to be determined. Due to controversy in the literature regarding the benefits of the biochemical mechanisms of various muscle mass supplements, such as L-leucine (including whey protein and BCAA), β-hydroxy-beta-methyl butyrate (HMβ), arginine, glutamine and creatine, several studies have carefully examined their effects. L-leucine and its derivatives appear to regulate protein synthesis by direct or indirect activation of the mTORC1 pool of kinases, further promoting muscle protein balance. Arginine and glutamine may act by reducing inflammation and infection progression, thus promoting improvements in food intake. Creatine exerts anabolic activity, acting as an immediate energy substrate to support muscle contraction further increasing lean mass, mainly due to greater water uptake by the muscle. In this narrative review, we highlighted the main findings regarding protein consumption and amino acids to mitigate cancer-induced skeletal muscle depletion.
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6.
Health-related quality of life across cancer cachexia stages.
Kasvis, P, Vigano, M, Vigano, A
Annals of palliative medicine. 2019;(1):33-42
Abstract
Cancer cachexia (CC) is common in advanced cancer and is accompanied by negative effects on health-related quality of life (HRQOL). However, methods to identify the impact of CC on HRQOL are limited. Single questionnaire items may provide insight on the effect of CC on HRQOL. Specifically, the use of "feeling of wellbeing" (FWB) on the Edmonton Symptom Assessment System (ESAS) questionnaire and the Distress Thermometer (DT) have been explored. Assessing how these two surrogate measures of HRQOL are impacted among CC stages and what drives these negative effects may allow for focused treatments. Five-hundred and twelve patients referred to a Cancer Rehabilitation Program completed the ESAS, with the question on FWB and the DT at baseline. Patients were separated into CC stages: non-cachexia (NC), pre-cachexia (PC), cachexia (C), refractory cachexia (RC). A mixed model ANOVA with post hoc Tukey adjustment was used to compare means of FWB and distress among the CC stages. To understand what was driving the differences between CC stages, a robust regression model was created with either distress or FWB as the outcome measure, dependent on the other measures in ESAS, age and sex. Finally, the use of cannabinoids in treating appetite loss was examined, as it has a detrimental effect on FWB; 54 patients underwent cannabinoid treatment for appetite loss within a community-based, physician-lead, medical cannabis clinic. A t-test to assess changes in ESAS appetite score after 3 months of cannabinoid treatment was examined. RC patients had a significantly poorer sense of wellbeing than the other cachexia stages (RC: 6.07±0.33). Significant differences in distress were identified between RC patients and those with NC and C, but not with PC (RC: 4.87±0.38, NC: 3.35±0.26, PC: 4.11±0.30, C: 3.60±0.28). FWB was negatively affected by worsening appetite in all CC stages except NC (PC: 0.19±0.08, P=0.022; C: 0.26±0.06, P<0.001; RC: 0.23±0.08, P=0.007). ESAS score for lack of appetite significantly improved between baseline (5.07±3.21) and follow-up (3.56±3.15, P=0.003) after cannabinoid treatment, with no significant difference in weight (baseline: 70.7±14.6 kg, 3-month follow-up: 71.0±14.8 kg). Future research should validate both multidimensional and single-item tools to measure HRQOL in patients at different stages of CC. Improvement of HRQOL via appetite stimulation, may be achieved through a multidisciplinary approach, which includes cannabinoid therapy.
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7.
Vitamin D, muscle recovery, sarcopenia, cachexia, and muscle atrophy.
Garcia, M, Seelaender, M, Sotiropoulos, A, Coletti, D, Lancha, AH
Nutrition (Burbank, Los Angeles County, Calif.). 2019;:66-69
Abstract
The relevance of vitamin D to skeletal muscle metabolism has been highlighted in recent years. The interest arises from the important findings of studies demonstrating multiple effects of vitamin D on this tissue, which can be divided into genomic (direct effects) and non-genomic effects (indirect effects). Another important aspect to be considered in the study of vitamin D and muscle fiber metabolism is related to different expression of vitamin D receptor (VDR), which varies in muscle tissue depending on age, sex, and pathology. The correlation between low circulating levels of vitamin D and muscle metabolism disorders is documented in various contexts, including muscle recovery, atrophy, sarcopenia, and cachexia. The aim of this review was to analyze recent results of both in vitro and in vivo studies to address the relationship between vitamin D and skeletal muscle biology. The words muscle atrophy, muscle hypertrophy, sarcopenia, and cachexia were crossed over with vitamin D in a Pubmed search. All original contributions, along with reviews on the topic, were included, and no publications in the past 10 y were discarded. The papers retrieved different topics such as vitamin D in skeletal muscle; vitamin D in circulation; vitamin D, sarcopenia, and muscle atrophy; vitamin D and cachexia; and vitamin D and muscle recovery.
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8.
Bioelectrical impedance vector analysis (BIVA) as a method to compare body composition differences according to cancer stage and type.
Nwosu, AC, Mayland, CR, Mason, S, Cox, TF, Varro, A, Stanley, S, Ellershaw, J
Clinical nutrition ESPEN. 2019;:59-66
Abstract
BACKGROUND & AIMS Bioelectrical impedance vector analysis (BIVA) is a non-invasive method of measuring human body composition. This offers the potential to evaluate nutritional and hydration states in cancer. Analysis of BIVA data using the z-score method (the number of standard deviations away from the mean value of the reference group) has the potential to facilitate comparisons between different cancer types. The aim of this study was to use the BIVA Reactance (R)/Reactance (Xc) z-score method to evaluate body composition differences in cancer, using data from previously published BIVA studies. METHODS Previous studies using BIVA in cancer were identified from the literature. Bioimpedance measurements were analysed using the BIVA RXc z-score graph. The mean impedance vectors from the studied populations were transformed into standard deviates (with respect to the mean and standard deviation of the reference populations). Body composition was classified according to vector placement (i.e. normal, athletic, cachectic, oedematous and dehydrated). RESULTS Seven male and three cancer female populations were evaluated. Body composition was classified as normal for the majority (n = 5), followed by cachexia (n = 4) and athletic (n = 1) respectively. Variation in body composition for the studied populations appeared to be related to gender, disease type and severity. CONCLUSIONS The BIVA RXc z-score method has potential to evaluate body composition differences between cancer groups. This method can study body composition, according to cancer type, stage, gender and ethnicity. Limitations of the method relate to issues concerning the appropriate use of reference populations and variability between bioimpedance analysers. Better body composition assessment has the potential to personalise therapeutic, nutritional and hydration management. Further work is essential to facilitate in-depth evaluation in these areas, in order to achieve meaningful use of BIVA in clinical practice.
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9.
Pancreas Cancer-Associated Weight Loss.
Hendifar, AE, Petzel, MQB, Zimmers, TA, Denlinger, CS, Matrisian, LM, Picozzi, VJ, Rahib, L, ,
The oncologist. 2019;(5):691-701
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Abstract
Unintentional weight loss in patients with pancreatic cancer is highly prevalent and contributes to low therapeutic tolerance, reduced quality of life, and overall mortality. Weight loss in pancreatic cancer can be due to anorexia, malabsorption, and/or cachexia. Proper supportive care can stabilize or reverse weight loss in patients and improve outcomes. We review the literature on supportive care relevant to pancreatic cancer patients, and offer evidence-based recommendations that include expert nutritional assessment, counseling, supportive measures to ensure adequate caloric intake, pancreatic enzyme supplementation, nutritional supplement replacement, orexigenic agents, and exercise. Pancreatic Cancer Action Network-supported initiatives will spearhead the dissemination and adoption of these best supportive care practices. IMPLICATIONS FOR PRACTICE Weight loss in pancreatic cancer patients is endemic, as 85% of pancreatic cancer patients meet the classic definition of cancer cachexia. Despite its significant prevalence and associated morbidity, there is no established approach to this disease entity. It is believed that this is due to an important knowledge gap in understanding the underlying biology and lack of optimal treatment approaches. This article reviews the literature regarding pancreas cancer-associated weight loss and establishes a new framework from which to view this complex clinical problem. An improved approach and understanding will help educate clinicians, improve clinical care, and provide more clarity for future clinical investigation.
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10.
[Overview of Cancer-Associated Cachexia].
Takayama, K
Gan to kagaku ryoho. Cancer & chemotherapy. 2019;(12):1814-1817
Abstract
Cachexia is well known to be a complication with malignant disease. The frequency of cancer-associated cachexia is different among various type of cancer, and relatively high in pancreas cancer, gastric cancer or lung cancer. The typical symptoms with cancer-associated cachexia includes body weight loss, appetite loss and general fatigue. In 2011, EPCRC published the consensus report of definition for cancer-associated cachexia in 2011, and the diagnostic criteria based on body weight loss is used widely. Although the systemic inflammation complicated with cancer plays an important role for cachexia development, basic research has clarified that cancer promotes cachexia directly using proteolysis inducing factor, lipid mobilizing factor and others. Recently, anamorelin, ghrelin mimics gathers attention as a treatment drug for cancer-associated cachexia. Clinical trials confirmed that anamorelin increased the lean body mass in cancer patients probably due to improve the appetite and protein anabolism. Treatment strategy for cancer-associated cachexia needs the comprehensive approach with nutritional and exercise therapy in addition with anti-cachexia drug.