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Irinotecan (CPT-11) and 5-fluorouracil (5-FU) are commonly used to treat metastatic colorectal cancer, but chemotherapy-associated steatosis/steatohepatitis (CASSH) frequently accompanies their use. The objective of this study was to determine effect of CPT-11+5-FU on liver toxicity, liver oxylipins, and cytokines, and to explore whether these alterations could be modified by dietary eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in the form of fish oil (EPA+DHA). Tumor-bearing animals were administered CPT-11+5-FU and maintained on a control diet or a diet containing EPA+DHA (2.3 g/100 g). Livers were collected one week after chemotherapy for the analysis of oxylipins, cytokines, and markers of liver pathology (oxidized glutathione, GSSH; 4-hydroxynonenal, 4-HNE, and type-I collagen fiber). Dietary EPA+DHA prevented the chemotherapy-induced increases in liver GSSH (p < 0.011) and 4-HNE (p < 0.006). Compared with the tumor-bearing animals, ten oxylipins were altered (three/ten n-6 oxylipins were elevated while seven/ten n-3 oxylipins were reduced) following chemotherapy. Reductions in the n-3 fatty-acid-derived oxylipins that were evident following chemotherapy were restored by dietary EPA+DHA. Liver TNF-α, IL-6 and IL-10 were elevated (p < 0.05) following chemotherapy; dietary EPA+DHA reduced IL-6 (p = 0.09) and eotaxin (p = 0.007) levels. Chemotherapy-induced liver injury results in distinct alterations in oxylipins and cytokines, and dietary EPA+DHA attenuates these pathophysiological effects.

Oat-based beverages are a nutritious product with the potential to support increased nutrient intake of patients with cancer. The aim of this research was to evaluate the sensory acceptance of oat-based beverages and perceptions of oats among patients with cancer as future vehicles for nutrient delivery. In study 1, three flavors of oat-beverages were well accepted without significant difference in liking among flavors or serving temperature, or between patients with cancer and healthy participants. Patients with cancer more frequently rated the beverages as too sweet compared to healthy participants; flavor intensity was just about right for all participants. In the second study, one of two formulations fortified with protein and fish oil was not different in liking compared to the unfortified chocolate product. Patients associated oat food products with specific oat-based food products and oat health benefits in a free-word association task in the third study. Together, sensory acceptance and the perceived health benefits of oats indicate the potential for oats to be incorporated in fortified and unfortified products tailored for patients with cancer. PRACTICAL APPLICATION: The three studies presented here to assess the sensory acceptance of oat-based beverages and perceptions of oats among patients with cancer demonstrate that oats can be incorporated in fortified and unfortified products tailored for patients with cancer. Inadequate nutrition is highly prevalent among oncology patients and there is a lack of available products targeted to improve their nutritional intake. These findings can support product developers and sensory scientists in the development and evaluation of food products acceptable to this population.

BACKGROUND Sarcopenia is defined as reduced skeletal muscle mass (SMM) or myopenia and altered muscle function and physical performance. It is unknown whether myopenia in children with end-stage liver disease (ESLD) adversely impacts clinical outcomes. We hypothesized that myopenia was prevalent in children with ESLD and related to suboptimal nutrition intake contributing to gross motor and growth delay, increased hospitalization, and medical complications. METHODS This retrospective study evaluated abdominal imaging (computed tomography/magnetic resonance imaging) for SMM (total, psoas, paraspinal, abdominal wall muscle; cm2 /height2 ) and adipose tissue (total, visceral, subcutaneous adipose tissue [SAT], ) determinations at the third and fourth lumbar vertebrates during liver transplantation (LTx) assessment. ESLD children (n = 30) were age- and gender-matched to healthy controls (n = 24). Myopenia was defined as SMM index z score 2 years), male children and was associated with gross motor delay, reduced energy intake, and increased hospitalization and infections (total/viral/fungal). CONCLUSIONS Myopenia, accompanied by low SAT in children with ESLD, is associated with adverse clinical outcomes. Rehabilitation strategies aimed at combating myopenia in children are important.

SummaryStructural plasticity in the brain often necessitates dramatic remodeling of neuronal processes and attendant reorganization of the cytoskeleton and membranes. While cytoskeletal restructuring has been studied extensively, how lipids might orchestrate structural plasticity remains unclear. We show that specific glial cells in Drosophila produce Glucocerebrosidase (GBA) to locally catabolize sphingolipids. Sphingolipid accumulation drives lysosomal dysfunction, causing gba1b mutants to harbor protein aggregates that cycle across circadian time and are regulated by neural activity, the circadian clock, and sleep. While the vast majority of membrane lipids are stable across the day, a specific subset, highly enriched in sphingolipids, cycles daily in a gba1b-dependant fashion. In parallel, circadian clock neurons remodel their neurites, growing and shrinking across the day to shape circadian behavior. Remarkably, this neuronal remodeling relies on a cycle of temporally offset sphingolipid biosynthesis and catabolism. Thus, dynamic sphingolipid regulation by glia enables diurnal circuit remodeling and proper circadian behavior.

Structural plasticity in the brain often necessitates dramatic remodeling of neuronal processes, with attendant reorganization of the cytoskeleton and membranes. Although cytoskeletal restructuring has been studied extensively, how lipids might orchestrate structural plasticity remains unclear. We show that specific glial cells in Drosophila produce glucocerebrosidase (GBA) to locally catabolize sphingolipids. Sphingolipid accumulation drives lysosomal dysfunction, causing gba1b mutants to harbor protein aggregates that cycle across circadian time and are regulated by neural activity, the circadian clock, and sleep. Although the vast majority of membrane lipids are stable across the day, a specific subset that is highly enriched in sphingolipids cycles daily in a gba1b-dependent fashion. Remarkably, both sphingolipid biosynthesis and degradation are required for the diurnal remodeling of circadian clock neurites, which grow and shrink across the day. Thus, dynamic sphingolipid regulation by glia enables diurnal circuit remodeling and proper circadian behavior.

Cancer treatment evokes impediments to liver metabolism that culminate in fatty liver. This study determined hepatic fatty acid composition and expression of genes and mediators involved in lipid metabolism following chemotherapy treatment. Female rats bearing the Ward colon tumor were administered Irinotecan (CPT-11) +5-fluorouracil (5-FU) and maintained on a control diet or a diet containing eicosapentaenoic acid (EPA) + docosahexaenoic acid (DHA) (2.3 g/100 g fish oil). Healthy animals provided with a control diet served as a reference group. Livers were collected one week after chemotherapy. Triacylglycerol (TG), phospholipid (PL), ten lipid metabolism genes, leptin, and IL-4 were measured. Chemotherapy increased TG content and reduced EPA content in the liver. Expression of SCD1 was upregulated by chemotherapy, while dietary fish oil downregulated its expression. Dietary fish oil down-regulated expression of the fatty acid synthesis gene FASN, while restoring the long chain fatty acid converting genes FADS2 and ELOVL2, and genes involved in mitochondrial β-oxidation (CPT1α) and lipid transport (MTTP1), to values similar to reference animals. Neither leptin nor IL-4 were affected by chemotherapy or diet. Depletion of EPA is associated with pathways evoking enhanced TG accumulation in the liver. Restoring EPA through diet may pose a dietary strategy to attenuate chemotherapy-associated impediments in liver fatty acid metabolism.

Emerging studies are reporting associations between skeletal muscle abnormalities and survival in cancer patients. Cancer prognosis is associated with depletion of essential fatty acids in erythrocytes and plasma in humans. However the relationship between skeletal muscle membrane fatty acid composition and survival is unknown. This study investigates the relationship between fatty acid content of phospholipids in skeletal muscle and survival in cancer patients. Rectus abdominis biopsies were collected during cancer surgery from 35 patients diagnosed with cancer. Thin-layer and gas chromatography were used for quantification of phospholipid fatty acids. Cutpoints for survival were defined using optimal stratification. Median survival was between 450 and 500 days when patients had arachidonic acid (AA) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in muscle phospholipid below the cut-point compared to 720–800 days for patients above. Cox regression analysis revealed that low amounts of AA, EPA and DHA are risk factors for death. The risk of death remained significant for AA [HR 3.5 (1.11–10.87), p = 0.03], EPA [HR 3.92 (1.1–14.0), p = 0.04] and DHA [HR 4.08 (1.1–14.6), p = 0.03] when adjusted for sex. Lower amounts of essential fatty acids in skeletal muscle membrane is a predictor of survival in cancer patients. These results warrant investigation to restore bioactive fatty acids in people with cancer.

Background: The concept of adipose tissue radiodensity is emerging and its relationship to disease prognosis has been infrequently explored. The aims of the present study were to evaluate published literature that explored adipose tissue radiodensity in relation to outcomes in health and disease and to summarize methodologies used to evaluate adipose tissue radiodensity by computed tomography (CT). Methods: A comprehensive literature review included all published studies that applied CT imaging of the abdominal region to define adipose tissue radiodensity. The review was performed without regard for study design or quality. Results: We identified 22 studies that evaluated the relationship between adipose tissue radiodensity and outcomes. The literature reviewed highlights significant methodological variation in terms of abdominal region selected, slice thickness, contrast media, dose, software, and radiodensity ranges used to define adipose tissues. This is primarily due to a lack of consensus about the effect such methodological variables have on body composition parameters. Conclusions: Authors should carefully report adipose tissue radiodensity, especially when it comes to prognosis inference. Consensus on methodology will enable meaningful advancement in understanding the importance of adipose tissue radiodensity in different disease conditions.

Fortified snacks can increase nutrient intake among patients with cancer. The aim of this study was to identify snack foods preferred as potential vehicles for fortification and how experienced symptoms influence preferences.A study-specific survey among 150 patients identified snack foods for fortification, influence of symptom presence, desired nutrients and characteristics of a fortified snack, and perception of oral nutritional supplements.Patients had mainly breast, gastrointestinal, lung, and colorectal tumors. Soup, yogurt, cheese, fruit juice, egg products, and protein bars were identified as suitable fortified snacks by60% of subjects. Desired characteristics for snacks included nutritious, flavorful, convenient, ready to eat, easy to chew, and easy to swallow. Vitamins, minerals, and protein were the nutrients of interest. Three clusters of symptoms were identified that predicted patients' desired characteristics of fortified snacks and satisfaction with food-related life. Patients in High and Moderate symptom clusters were more likely to have reduced food intake and higher consumption of oral nutritional supplements.Preferences for fortified snacks and their characteristics are influenced by symptom presence. The results of this study provide insight to guide the development of fortified snacks for patients with cancer.

Sarcopenia (severe muscle depletion) is a prevalent muscle abnormality in patients with cirrhosis that confers poor prognosis both pre- and post-liver transplantation. The pathogenesis of sarcopenia is multifactorial and results from an imbalance between protein synthesis and breakdown. Nutritional, metabolic, and biochemical abnormalities seen in chronic liver disease alter whole body protein homeostasis. Hyperammonemia, increased autophagy, proteasomal activity, lower protein synthesis, and impaired mitochondrial function play an important role in muscle depletion in cirrhosis. Factors including cellular energy status, availability of metabolic substrates (e.g., branched-chain amino acids), alterations in the endocrine system (insulin resistance, circulating levels of insulin, insulin-like growth factor-1, corticosteroids, and testosterone), cytokines, myostatin, and exercise are involved in regulating muscle mass. A favored atrophy of type II fast-twitch glycolytic fibers seems to occur in patients with cirrhosis and sarcopenia. Identification of muscle biological abnormalities and underlying mechanisms is required to plan clinical trials to reverse sarcopenia through modulation of specific mechanisms. Accordingly, a combination of nutritional, physical, and pharmacological interventions might be necessary to reverse sarcopenia in cirrhosis. Moderate exercise should be combined with appropriate energy and protein intake, in accordance with clinical guidelines. Interventions with branched chain amino acids, testosterone, carnitine, or ammonia-lowering therapies should be considered individually. Various factors such as dose, type, duration of supplementations, etiology of cirrhosis, amount of dietary protein intake, and compliance with supplementation and exercise should be the focus of future large randomized controlled trials investigating both prevention and treatment of sarcopenia in this patient population.

BACKGROUND: Researchers increasingly use intraoperative muscle biopsy to investigate mechanisms of skeletal muscle atrophy in patients with cancer. Muscles have been assessed for morphological, cellular, and biochemical features. The aim of this study was to conduct a state-of-the-science review of this literature and, secondly, to evaluate clinical and biological variation in biopsies of rectus abdominis (RA) muscle from a cohort of patients with malignancies.METHODS: Literature was searched for reports on muscle biopsies from patients with a cancer diagnosis. Quality of reports and risk of bias were assessed. Data abstracted included patient characteristics and diagnoses, sample size, tissue collection and biobanking procedures, and results. A cohort of cancer patients (n = 190, 88% gastrointestinal malignancies), who underwent open abdominal surgery as part of their clinical care, consented to RA biopsy from the site of incision. Computed tomography (CT) scans were used to quantify total abdominal muscle and RA cross-sectional areas and radiodensity. Biopsies were assessed for muscle fibre area (μm2 ), fibre types, myosin heavy chain isoforms, and expression of genes selected for their involvement in catabolic pathways of muscle.RESULTS: Muscle biopsy occurred in 59 studies (total N = 1585 participants). RA was biopsied intraoperatively in 40 studies (67%), followed by quadriceps (26%; percutaneous biopsy) and other muscles (7%). Cancer site and stage, % of male participants, and age were highly variable between studies. Details regarding patient medical history and biopsy procedures were frequently absent. Lack of description of the population(s) sampled and low sample size contributed to low quality and risk of bias. Weight-losing cases were compared with weight stable cancer or healthy controls without considering a measure of muscle mass in 21 out of 44 studies. In the cohort of patients providing biopsy for this study, 78% of patients had preoperative CT scans and a high proportion (64%) met published criteria for sarcopenia. Fibre type distribution in RA was type I (46% ± 13), hybrid type I/IIA (1% ± 1), type IIA (36% ± 10), hybrid type IIA/D (15% ± 14), and type IID (2% ± 5). Sexual dimorphism was prominent in RA CT cross-sectional area, mean fibre cross-sectional area, and in expression of genes associated with muscle growth, apoptosis, and inflammation (P < 0.05). Medical history revealed multiple co-morbid conditions and medications.CONCLUSIONS: Continued collaboration between researchers and cancer surgeons enables a more complete understanding of mechanisms of cancer-associated muscle atrophy. Standardization of biobanking practices, tissue manipulation, patient characterization, and classification will enhance the consistency, reliability, and comparability of future studies.

Background Identifying children at malnutrition risk on admission to hospital is considered best practice; however, nutrition screening in pediatric populations is not common. The aim of this study was to determine which screening tool is able to identify children with malnutrition on admission to hospital. Methods A nurse administered 2 pediatric nutrition screening tools, Screening Tool for Risk on Nutritional Status and Growth (STRONGkids) and Pediatric Nutrition Screening Tool (PNST) to patients admitted to medicine and surgery units (n = 165). The Subjective Global Nutritional Assessment (SGNA) was then completed by a dietitian, blinded to the results of the screens. Sensitivity, specificity, and κ were calculated for both screening tools against the SGNA. A receiver operating characteristic (ROC) curve assessed alternate cutoffs for each tool. Length of hospital stay (LOS) was used to assess prospective validity. Results Using the recommended cutoffs, the sensitivity of STRONGkids was 89%, specificity 35%, and κ 0.483. The sensitivity of PNST was 58%, specificity 88%, and κ 0.601. Using adjusted cutoffs, PNST's sensitivity improved to 87%, specificity 71%, and κ 0.681, and STRONGkids specificity improved to 61%, sensitivity 80%, and κ 0.5. Children identified at nutrition risk had significantly longer LOS (P < 0.05). Conclusion This study showed neither tool was appropriate for clinical use based on published cutoffs. By adjusting the cutoffs using ROC curve analysis, both tools improved overall agreement with the SGNA without significantly impacting the prospective validity. PNST with adjusted cutoffs is the most appropriate for clinical use in this population.

The objective of this study was to investigate if DHA dietary supplementation enhances the anticancer actions of docetaxel (TXT) in two different drug resistant triple negative breast cancer (TNBC) patient-derived xenografts (PDX)s. In two experiments, female NSG mice bearing TNBC PDXs were randomized to one of two nutritionally adequate diets (20% w/w): control (0% DHA), or DHA (3.9% w/w of total fat) and injected with 0 or 5 mg/kg TXT, twice weekly for 6 weeks (n = 8 per group). Treatment response was determined by significant differences in tumor weight, and apoptotic, proliferation and cell cycle markers at endpoint. Mice bearing MAXF574 xenografts fed DHA diet and treated with TXT had a 57% reduction in tumor weight compared to mice fed control diet (P

Background Most prognostic scoring systems for colorectal liver metastases (CRLMs) account for factors related to tumour biology. Little is known about the effects of the host phenotype to the tumour. Our objective was to delineate the relationship of systemic inflammation and body composition features [i.e. low skeletal muscle mass (sarcopenia) and low visceral adipose tissue (VAT)], two well-described host phenotypes in cancer. Methods Clinical data and pre-operative blood samples were collected from 99 patients who underwent resection of CRLM. Pre-operative computed tomography scans were available for 97 patients; body composition was analysed at the L3 level, stratified for sex and age. Clinicopathological variables, serum C-reactive protein (CRP), and various body composition variables were evaluated. Overall survival was evaluated as a function of these same variables in multivariate Cox regression analysis. Results Skeletal muscle was significantly correlated with VAT (r = 0.46, P = 5 mg/mL) in 42 patients (43.3%). Elevated CRP was more common in patients with sarcopenia (73.8% vs. 51.1%, P = 0.029). The most significant prognostic factors were the coincidence of elevated CRP and adverse body composition features (sarcopenia and/or low VAT; hazard ratio 4.3, 95% confidence interval 1.5-13.0, P = 0.008), as well as Fong clinical prognostic score (hazard ratio 2.9, 95% confidence interval 1.5-5.5, P = 0.002). Conclusions Body composition in patients with CRLM is not directly linked to the presence of systemic inflammation. However, when systemic inflammation coincides with sarcopenia and/or low VAT, prognosis is adversely affected, independent of the Fong clinical prognostic score.

Since 2007, a quantitative, specific and precise approach to the detection of muscle loss has become accessible with the advent of image-based assessments. Computed tomography images acquired as part of standard cancer care are the serendipitous substrate for these analyses. Three radiologically-determined abnormalities, sarcopenia (severe muscle depletion), catabolic loss of muscle over time, and reduced muscle radiation attenuation associate with progressive functional impairment, treatment-related complications, reduced quality of life, and mortality. Fundamental understanding of muscle wasting in cancer cachexia has been developed on a base of clinical and experimental studies, which have identified alterations in muscle protein synthesis, autophagy and ubiquitin-mediated proteolysis as key contributors to muscle loss. The etiology of cancer-associated muscle wasting is multifactorial. Tumor metabolism captures energy fuels and amino acids, and a suite of tumor-derived molecules elicits catabolic pathways at the tissue level in muscle. Endocrine, neural and inflammatory derangements add further catabolic drive. Antineoplastic agents make a substantial contribution to muscle wasting by directly action on muscle cells, as well as secondarily via their systemic side effects. Encouraging data is emerging as to the potential reversibility of muscle loss and/or reduced muscle radiation attenuation through modulation of specific mechanisms. In the first line, pain and symptom management is a key element of the prevention of catabolic loss of muscle. Intake of intake of high-quality proteins and ω-3 polyunsaturated fatty acids support retention or gain of muscle mass. While there is no approved drug therapy for the indication of cancer-associated muscle wasting, there is preliminary evidence for robust gain of skeletal muscle mass in research studies of new therapeutics including inhibitors of mitogen-activated protein kinase kinases and ghrelin receptor agonists.

Fatty liver is a side effect of chemotherapy that limits the ability to treat colorectal cancer (CRC) patients in the most effective way. The aim of this study was to determine hepatic fatty acid composition and expression of genes involved in lipid metabolism at two time points following sequential chemotherapy treatment with Irinotecan (CPT-11)+5-fluorouracil (5-FU), agents commonly used to treat human colorectal cancer. Female Fischer 344 rats were provided a semi-purified AIN-76 basal diet with modified fat component. One cycle of chemotherapy consisted of CPT-11+5-FU and was initiated 2 weeks after tumor implantation (D0); a second cycle was given one week later. Two days after each cycle (Day 2 and Day 9), animals were euthanized, and livers collected. Triacylglycerol (TAG) and phospholipid (PL) fractions were isolated using thin layer chromatography and fatty acids (FAs) were quantified using gas chromatography. Expression of 44 lipid metabolism genes were analyzed by qPCR. Total liver TAG level was lowest after the second cycle D0 and D2 (P = 0.05) characterized by lower content of n-6 and n-3 polyunsaturated fatty acids (PUFAs). N-6 PUFAs significantly declined with subsequent treatments. Of 44 genes analyzed, 13 genes were altered with CPT-11+5-FU treatment. Expression of genes VLCAD and DGAT1, involved in fatty acid oxidation as well as DGAT1 in TAG synthesis, were significantly elevated after each cycle, whereas expression of genes ELOVL2 and FADS2, involved in fatty acid elongation and desaturation were significantly lower at D9 compared to D2 and D0 (P

Background: Emerging studies are reporting associations between skeletal muscle abnormalities and survival in cancer patients. Cancer prognosis is associated with depletion of essential fatty acids in membrane of blood plasma and serum in humans, however the relationship between skeletal muscle membrane fatty acid composition and survival is unknown. This study investigates the relationship between fatty acid content of phospholipids in skeletal muscle and survival in cancer patients.Methods: Rectus abdominis biopsies were collected during cancer surgery from 35 patients diagnosed with cancer. Thin-layer and gas chromatography were used for quantification of phospholipid fatty acid content of the muscle. Cut-points for fatty acids were established using optimal stratification.Results: Median survival was between 450-500 days when patients had arachidonic acid (AA) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in muscle phospholipid above the cut-point compared to 720-800 days for patients below. Cox regression analysis revealed that low amounts of AA, EPA and DHA are risk factors for death. The risk of death remained significant for AA [HR 3.5 (1.11-10.87), p=0.03], EPA [HR 3.92 (1.1-14.0), p=0.04] and DHA [HR 4.08 (1.1-14.6), p=0.03] when adjusted for sex. Conclusion: Lower amount of essential fatty acids in skeletal muscle membrane is predictor of survival in cancer patients. These results warrant investigation to restore depletion of bioactive fatty acids in cancer.

Skeletal muscle is composed of multinuclear cells called myofibres, which are formed by the fusion of myoblasts during development. The size of the muscle fiber and mass of skeletal muscle are altered in response to several pathological and physiological conditions. Skeletal muscle regeneration is primarily mediated by muscle stem cells called satellite cells (SCs). In response to injury, these SCs replenish myogenic progenitor cells to form new myofibers to repair damaged muscle. During myogenesis, activated SCs proliferate and differentiate to myoblast and then fuse with one another to form muscle fibers. A reduced number of SCs and an inability to undergo myogenesis may contribute to skeletal muscle disorders such as atrophy, cachexia, and sarcopenia. Myogenic regulatory factors (MRF) are transcription factors that regulate myogenesis and determines whether SCs will be in the quiescent, activated, committed, or differentiated state. Mitochondria oxidative phosphorylation and oxidative stress play a role in the determination of the fate of SCs. The potential activation and function of SCs are also affected by inflammation during skeletal muscle regeneration. Omega-3 polyunsaturated fatty acids (PUFAs) show promise to reduce inflammation, maintain muscle mass during aging, and increase the functional capacity of the muscle. The aim of this critical review is to highlight the role of omega-3 PUFAs on the myogenic differentiation of SCs and pathways affected during the differentiation process, including mitochondrial function and inflammation from the current body of literature.

Simple Summary There has been extensive research into the beneficial anticancer effects of n-3 long-chain polyunsaturated fatty acids (LCPUFA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in preclinical models of cancer. However, clinical evidence is limited. The aim of this scoping review was to summarize the current clinical evidence of n-3 LCPUFA supplementation in cancer treatment and highlight areas where more clinical evidence is needed. We summarized the results of 57 clinical trials with an EPA/DHA intervention and determined that supplementation could improve a variety of outcomes important to the patient and the disease process, including immune system modulation, improved weight maintenance and increased disease-free or progression-free survival. There is, however, a need for larger, well-controlled, statistically powered randomized controlled trials to move n-3 supplementation to clinical practice. Abstract This scoping review examines the evidence for n-3 long-chain polyunsaturated fatty acid [LCPUFA, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)] supplementation in clinical cancer therapy. A comprehensive literature search was performed to identify relevant clinical intervention studies conducted through August 2020. Fifty-seven unique cancer trials, assessing EPA and/or DHA supplementation pre- or post-treatment, concomitant with neoadjuvant chemotherapy, radiation or surgery, or in palliative therapy were included. Breast, head and neck, gastrointestinal, gastric, colorectal/rectal, esophageal, leukemia/lymphoma, lung, multiple myeloma and pancreatic cancers were investigated. Across the spectrum of cancers, the evidence suggests that supplementation increased or maintained body weight, increased progression-free and overall survival, improved overall quality of life, resulted in beneficial change in immune parameters and decreased serious adverse events. Taken together, the data support that EPA and/or DHA could be used to improve outcomes important to the patient and disease process. However, before incorporation into treatment can occur, there is a need for randomized clinical trials to determine the dose and type of n-3 LCPUFA intervention required, and expansion of outcomes assessed and improved reporting of outcomes.

Pre-operative nutrition screening is recommended to identify cancer patients at risk of malnutrition, which is associated with poor outcomes. Low muscle mass (sarcopenia) and lipid infiltration to muscle cells (myosteatosis) are similarly associated with poor outcomes but are not routinely screened for. We investigated the prevalence of sarcopenia and myosteatosis across the nutrition screening triage categories of the Patient-Generated Subjective Global Assessment Short Form (PG-SGASF) in a pre-operative colorectal cancer (CRC) cohort. Data were prospectively collected from patients scheduled for surgery at two sites in Edmonton, Canada. PG-SGASF scores &ge, 4 identified patients at risk for malnutrition, sarcopenia and myosteatosis were identified using computed-tomography (CT) analysis. Patients (n = 176) with a mean age of 63.8 &plusmn, 12.0 years, 52.3% male, 90.3% with stage I&ndash, III disease were included. Overall, 25.2% had PG-SGASF score &ge, 4. Sarcopenia alone, myosteatosis alone or both were identified in 14.0%, 27.3%, and 6.4% of patients, respectively. Sarcopenia and/or myosteatosis were identified in 43.4% of those with PG-SGASF score &lt, 4 and in 58.5% of those with score &ge, 4. Overall, 32.9% of the cohort had sarcopenia and/or myosteatosis with PG-SGASF score &lt, 4. CT-defined sarcopenia and myosteatosis are prevalent in pre-operative CRC patients, regardless of the presence of traditional nutrition risk factors (weight loss, problems eating), therefore, CT image analysis effectively adds value to nutrition screening by identifying patients with other risk factors for poor outcomes.

Summary During cancer therapy many patients experience significant malnutrition, leading to decreased tolerance to chemotherapy and decreased survival. Dietary citrulline supplementation improves nutritional status in situations such as short bowel syndrome and aging, and is of potential interest in oncology. However, a mandatory prerequisite is to test this amino acid for interaction with tumor growth and chemotherapy response. Dietary citrulline (Cit; 2%), or an isonitrogenous mix of non-essential amino acids (control), was given to Ward colon tumor-bearing rats the day before chemotherapy initiation. Chemotherapy included 2 cycles, one week apart, each consisting of one injection of CPT-11 (50 mg/kg) and of 5-fluorouracil (50 mg/kg) the day after. Body weight, food intake and tumor volume were measured daily. The day after the last injection, rats were killed, muscles (EDL, gastrocnemius), intestinal mucosa, tumor, spleen and liver were weighed. Muscle and intestinal mucosa protein content were measured. Phosphorylated 4E-BP1 was measured in muscle and tumor as a surrogate for biosynthetic activation. FRAPS (Ferric Reducing Ability of Plasma) and thiols in plasma, muscle and tumor were evaluated and plasma amino acids and haptoglobin were measured. Numerous parameters did not differ by diet overall: a) response of tumor mass to treatment, b) tumor antioxidants and phosphorylated 4E-BP1 levels, c) relative body weight and relative food intake, d) weight of EDL, gastrocnemius, intestinal mucosa, spleen and liver and e) plasma haptoglobin concentrations. Moreover, plasma citrulline concentration was not correlated to relative body weight, only cumulated food intake and plasma haptoglobin concentrations were correlated to relative body weight. Citrulline does not alter the tumor response to CPT-11/5FU based therapy but, has no effect on nutritional status, which could be due to the anorexia and the low amount of citrulline and protein ingested.

Summary Background & aims Pre-clinical studies suggest that 16:4(n-3) in purified form or as a component of fish oil might induce platinum-based chemotherapy resistance. Our aim was to determine plasma total and free 16:4(n-3) before and during platinum-based chemotherapy in non-small cell lung cancer (NSCLC) patients supplemented with fish oil or provided standard care, and to explore relationships between plasma 16:4(n-3) levels and tumor response to treatment. Methods In a retrospective, secondary data analysis of a prior clinical trial, plasma from patients with NSCLC (n = 21) who underwent platinum-based chemotherapy and were assigned to 2.2 g/day of eicosapentaenoic (EPA) plus 1.1 g DHA/day as fish oil (FO; n = 12) or received no intervention (standard care; SC; n = 9). Plasma 16:4(n-3) was quantified as free and esterified (total) fatty acid using HPLC-MS/MS. Plasma 16:4(n-3) levels were evaluated over time in relation to fish oil supplementation and response to platinum-based therapy, and compared with a group of healthy subjects (REF; n = 11). Results Plasma 16:4(n-3) was detected in all samples. The percentage change/day in plasma esterified (total) 16:4(n-3) was higher for FO versus SC group (2.7 versus −1.8%/d, U = 20, p = 0.02), but change in plasma free 16:4(n-3) was not different between FO and SC. Median plasma free and esterified 16:4(n-3) were similar between responders and non-responders to platinum-based chemotherapy. Total and free plasma 16:4(n-3) fatty acids were similar between NSCLC patients and REF (NSCLC vs REF: total 16:4(n-3): 122.9 vs. 95.2 nM and free 16:4(n-3) 23.9 vs. 27.6 nM). Conclusions This first of its kind study that evaluated plasma 16:4(n-3) in NSCLC patients showed that 16:4 (n-3) was elevated during FO supplementation, independent of fish oil supplementation or platinum-based chemotherapy.

Summary Cancer-associated cachexia is a complex metabolic syndrome characterized by weight loss and systemic inflammation. Muscle loss and fatty infiltration into muscle are associated with poor prognosis in cancer patients. Skeletal muscle secretes myokines, factors with autocrine, paracrine and/or endocrine action, which may be modified by or play a role in cachexia. This study examined myokine content in the plasma, skeletal muscle and tumor homogenates from treatment-naive patients with gastric or colorectal stages I-IV cancer with cachexia (CC, N = 62), or not (weight stable cancer, WSC, N = 32). Myostatin, interleukin (IL) 15, follistatin-like protein 1 (FSTL-1), fatty acid binding protein 3 (FABP3), irisin and brain-derived neurotrophic factor (BDNF) protein content in samples was measured with Multiplex technology; body composition and muscle lipid infiltration were evaluated in computed tomography, and quantification of triacylglycerol (TAG) in the skeletal muscle. Cachectic patients presented lower muscle FSTL-1 expression (p = 0.047), higher FABP3 plasma content (p = 0.0301) and higher tumor tissue expression of FABP3 (p = 0.0182), IL-15 (p = 0.007) and irisin (p = 0.0110), compared to WSC. Neither muscle TAG content, nor muscle attenuation were different between weight stable and cachectic patients. Lumbar adipose tissue (AT) index, visceral AT index and subcutaneous AT index were lower in CC (p = 0.0149, p = 0.0455 and p = 0.0087, respectively), who also presented lower muscularity in the cohort (69.2% of patients; p = 0.0301), compared to WSC. The results indicate the myokine profile in skeletal muscle, plasma and tumor is impacted by cachexia. These findings show that myokines eventually affecting muscle wasting may not solely derive from the muscle itself (as the tumor also may contribute to the systemic scenario), and put forward new perspectives on cachexia treatment targeting myokines and associated receptors and pathways.

Providing eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), in the form of fish oils, to benefit muscle is an emerging area of interest. The aim of this work was to evaluate the current literature that has assessed muscle mass as an outcome during a fish oil intervention in any chronic disease.The vast majority of studies published in the last 3 years (12 of 15) have been conducted in the oncological setting, in patients undergoing treatment for cancers of the gastrointestinal tract, breast, head and neck, lung, cervix, and hematological cancers. Three studies were conducted in patients with chronic obstructive pulmonary disease (COPD). Fish oil was provided as part of nutrient mixtures in 12 studies and as capsules in three studies.Overall, the evidence for an effect of fish oil supplementation on muscle mass in patients with cancer undergoing treatment and in COPD remains unequivocal and reveals limited new knowledge in the area of fish oil supplementation in the cancer setting. Recent literature continues to provide mixed evidence on the efficacy of fish oil on muscle mass and function. The present review highlights challenges in comparing and interpreting current studies aimed at testing fish oil supplementation for muscle health.

Background Recent advances in evaluation of body composition show body mass index to be inadequate in differentiating between body compartments in cirrhosis. Given the limitations of body mass index, body composition evaluation using computed tomography has been increasingly used as a non-invasive clinical tool with prognostic value. Another factor influencing prognosis includes sex-specific differences in body composition that are seen in cirrhosis. Aim To review current knowledge regarding the frequency and clinical implications of abnormal body composition features in cirrhosis. Methods We searched PubMed database and limited the literature search to full-text papers published in English. The expertise of review authors in analysing body composition was used to eliminate studies using inappropriate landmarks or demarcation of body composition components on computed tomography images. Results Sarcopenia is a well established factor affecting morbidity and mortality in cirrhosis. Other important body composition components that have been over looked thus far include subcutaneous adipose tissue and visceral adipose tissue. Female patients with cirrhosis and low subcutaneous adiposity have a higher risk of mortality, whereas male patients with high visceral adiposity have a higher risk of hepatocellular carcinoma and recurrence following liver transplantation. Increased adipose tissue radiodensity has been associated with risk of decompensation and mortality. Conclusions Further evaluation of body composition abnormalities may help with development of targeted therapeutic strategies and improve outcome in patients with cirrhosis. Moreover, recognition of these abnormalities could improve prioritisation for liver transplantation as our current method based solely on liver function might lead to risk misclassification.

PURPOSE OF REVIEW: Providing eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), in the form of fish oils, to benefit muscle is an emerging area of interest. The aim of this work was to evaluate the current literature that has assessed muscle mass as an outcome during a fish oil intervention in any chronic disease. RECENT FINDINGS: The vast majority of studies published in the last 3 years (12 of 15) have been conducted in the oncological setting, in patients undergoing treatment for cancers of the gastrointestinal tract, breast, head and neck, lung, cervix, and hematological cancers. Three studies were conducted in patients with chronic obstructive pulmonary disease (COPD). Fish oil was provided as part of nutrient mixtures in 12 studies and as capsules in three studies. SUMMARY: Overall, the evidence for an effect of fish oil supplementation on muscle mass in patients with cancer undergoing treatment and in COPD remains unequivocal and reveals limited new knowledge in the area of fish oil supplementation in the cancer setting. Recent literature continues to provide mixed evidence on the efficacy of fish oil on muscle mass and function. The present review highlights challenges in comparing and interpreting current studies aimed at testing fish oil supplementation for muscle health.