Weight-losing Patients Research Articles

The prognostic value of weight and body composition changes in patients with non-small-cell lung cancer treated with nivolumab.

BackgroundIt is not well known to what extent effectiveness of treatment with immune checkpoint inhibitors in stage IV non‐small‐cell lung cancer (NSCLC) is influenced by weight loss and changes in body composition. Therefore, the goal of this study was to evaluate body composition changes in relation to early weight change and overall survival (OS) in stage IV NSCLC patients treated with second‐line nivolumab.MethodsAll patients with stage IV NSCLC, who were treated with second‐line nivolumab between June 2015 and December 2018 at Maastricht University Medical Center, were evaluated. Skeletal muscle mass (SMM), visceral adipose tissue (VAT), and subcutaneous adipose tissue (SAT) were assessed at the first lumbar level on computed tomography images obtained before initiation of nivolumab and at week 6 of treatment. The contribution of changes in body weight (defined as >2% loss), SMM, VAT, and SAT to OS was analysed by Kaplan–Meier method and adjusted for clinical confounders in a Cox regression analysis. The results from the study cohort were validated in another Dutch cohort from Erasmus Medical Center, Rotterdam.ResultsOne hundred and six patients were included in the study cohort. Loss of body weight of >2% at week 6 was an independent predictor for poor OS (hazard ratio 2.39, 95% confidence interval 1.51–3.79, P < 0.001) when adjusted for gender, >1 organ with metastasis, pretreatment hypoalbumenaemia, and pretreatment elevated C‐reactive protein. The result was confirmed in the validation cohort (N = 62). Loss of SMM as a feature of cancer cachexia did not significantly predict OS in both cohorts. Significant (>2%) weight loss during treatment was reflected by a significant loss of VAT and SAT, while loss of SMM was comparable between weight‐stable and weight‐losing patients.ConclusionsWeight loss, characterized by loss of subcutaneous and visceral adipose tissues, at week 6 of treatment with nivolumab, is a significant poor prognostic factor for survival in patients with Stage IV NSCLC.

Longitudinal alterations in nutrient intake and food pattern in patients with non-small cell lung cancer during anti-neoplastic treatment: a cohort study.

Unintentional weight loss is frequently observed in cancer patients. Nutritional therapy is essential, and dietary counselling is the first step. The present study aimed to explore the nutrient intake and food patterns in weight-stable and weight-losing patients with non-small cell lung cancer (NSCLC) during anti-neoplastic treatment. Patients with NSCLC (n=62) were observed during first-line systemic anti-neoplastic treatment. Body weight and dietary intake were assessed on the first and second cycle, and after completing three cycles of treatment. Longitudinal changes were analysed in three groups: weight stable, weight losers and mixed weight. Nutrient intake did not change during treatment in weight stable, although weight losers significantly increased the relative protein intake. Weight stable maintained the food pattern during treatment apart from a decreased consumption of oral nutritional support (ONS). At baseline, weight losers were characterised by pretreatment weight loss, high consumption of ONS, as well as low consumption of grains and animal products. During treatment, weight losers increased the consumption of protein, fatty foods and ONS but decreased the consumption of sweets and alcohol. Large heterogeneity in nutrient and food intake was observed in NSCLC patients during anti-neoplastic treatment. Weight losers and weight stable had a similar nutrient intake although protein intake increased in weight losers. Grains and animal products were lower and ONS higher in weight losers compared to weight stable during treatment. Weight losers further increased the consumption of ONS and fatty foods, while the consumption of sweets and alcohol decreased during treatment.

Habitual Myofibrillar Protein Synthesis Is Normal in Patients with Upper GI Cancer Cachexia.

Skeletal muscle wasting and weight loss are characteristic features of cancer cachexia and contribute to impaired function, increased morbidity, and poor tolerance of chemotherapy. This study used a novel technique to measure habitual myofibrillar protein synthesis in patients with cancer compared with healthy controls. An oral heavy water (87.5 g deuterium oxide) tracer was administered as a single dose. Serum samples were taken over the subsequent week followed by a quadriceps muscle biopsy. Deuterium enrichment was measured in body water, serum alanine, and alanine in the myofibrillar component of muscle using gas chromatography-pyrolysis-isotope ratio mass spectrometry and the protein synthesis rate calculated from the rate of tracer incorporation. Net change in muscle mass over the preceding 3 months was calculated from serial CT scans and allowed estimation of protein breakdown. Seven healthy volunteers, 6 weight-stable, and 7 weight-losing (≥5% weight loss) patients undergoing surgery for upper gastrointestinal cancer were recruited. Serial CT scans were available in 10 patients, who lost skeletal muscle mass preoperatively at a rate of 5.6%/100 days. Myofibrillar protein fractional synthetic rate was 0.058%, 0.061%, and 0.073%/hour in controls, weight-stable, and weight-losing patients, respectively. Weight-losing patients had higher synthetic rates than controls (P = 0.03). Contrary to previous studies, there was no evidence of suppression of myofibrillar protein synthesis in patients with cancer cachexia. Our finding implies a small increase in muscle breakdown may account for muscle wasting.

Tailoring the nutritional regimen in the elderly cancer patient

Our knowledge of the macronutrient requirement of elderly cancer patient is still incomplete and mainly relies on studies of elderly (healthy) people and populations of cancer patients including both adult and elderly subjects. Patients with minor nutritional deterioration do not require any specific nutritional regimen, but cachectic patients do. Total energy expenditure can be unchanged or lower in advanced weight-losing patients (when compared with matched healthy controls) because the higher resting metabolic expenditure can be offset by reduced physical activity, and it approximates to 25-28 Kcal/kg/d. Protein requirement is probably 1.5 g amino acid (AA)/kg/d or more, especially if the goal is increased lean body mass. However, the final balance depends not only on the quantity of AA but also their quality: diets including a high percentage of essential AA and especially of branched-chain ones and leucine in particular, are advocated. Total fluid load should be prudent, around 25-30 ml/kg/d.

Weight loss and resting energy expenditure in male patients with newly diagnosed esophageal cancer

ObjectivesCancer cachexia is associated with impaired nutritional status and systemic inflammation. The goal of this study was to evaluate the nutritional status and resting energy expenditure (REE) changes in patients with newly detected esophageal cancer, and the influence of weight loss on REE. MethodsFifty-six patients and 30 healthy controls were prospectively enrolled, and patients were further divided into weight-stable (WS) and weight-loss (WL) subgroups. Body composition, measured REE (mREE), and the ratio of mREE to predicted REE (pREE) by Harris-Benedict formula were assessed. Blood levels of hemoglobin, albumin, prealbumin, high-sensitivity C-reactive protein (hs-CRP), tumor necrosis factor-alpha (TNF-α), and interleukin (IL)-6 were measured in patients. ResultsCancer patients had lower body mass index (BMI) and percentage of fat mass, but higher mREE and percentage of mREE/pREE compared with healthy controls (P < 0.05). WS (n = 32) and WL patients (n = 24) had similar BMI and body composition indices, but the latter had obviously higher mREE, mREE per kilogram body weight (mREE/BW), percentage of mREE/pREE, hs-CRP and IL-6 levels, and lower albumin and prealbumin levels. Percentage of weight loss was positively correlated with REE/BW, hs-CRP, and IL-6 level (r = 0.238, P = 0.044; r = 0.446, P = 0.01; r = 0.196, P = 0.047, respectively). ConclusionImpaired nutrition status, elevated energy expenditure, and higher inflammation status tend to be apparent in weight-losing patients with newly diagnosed esophageal cancer, which suggested that early recognition of body weight change and routine nutritional risk screening followed by adequate nutrition intervention should be applied in these patients.

Diagnostic accuracy of a validated screening tool for monitoring nutritional status in patients with colorectal cancer: a systematic review protocol

Diagnostic accuracy of a validated screening tool for monitoring nutritional status in patients with colorectal cancer: a systematic review protocol

Suppression of Skeletal Muscle Turnover in Cancer Cachexia: Evidence from the Transcriptome in Sequential Human Muscle Biopsies

The mechanisms underlying muscle wasting in patients with cancer remain poorly understood, and consequently there remains an unmet clinical need for new biomarkers and treatment strategies. Microarrays were used to examine the transcriptome in single biopsies from healthy controls (n = 6) and in paired biopsies [pre-resection baseline (weight-loss 7%) and 8 month post-resection follow-up (disease-free/weight-stable for previous 2 months)] from quadriceps muscle of patients with upper gastrointestinal cancer (UGIC; n = 12). Before surgery, 1,868 genes were regulated compared with follow-up (false discovery rate, 6%). Ontology analysis showed that regulated genes belonged to both anabolic and catabolic biologic processes with overwhelming downregulation in baseline samples. No literature-derived genes from preclinical cancer cachexia models showed higher expression in baseline muscle. Comparison with healthy control muscle (n = 6) revealed that despite differences in the transcriptome at baseline (941 genes regulated), the muscle of patients at follow-up was similar to control muscle (2 genes regulated). Physical activity (step count per day) did not differ between the baseline and follow-up periods (P = 0.9), indicating that gene expression differences reflected the removal of the cancer rather than altered physical activity levels. Comparative gene expression analysis using exercise training signatures supported this interpretation. Metabolic and protein turnover-related pathways are suppressed in weight-losing patients with UGIC whereas removal of the cancer appears to facilitate a return to a healthy state, independent of changes in the level of physical activity.

An unblinded randomised controlled trial of preoperative oral supplements in colorectal cancer patients

Perioperative oral supplementation has been shown to reduce post-operative complications. However, the use of preoperative standard oral supplements in a cohort of colorectal cancer patients has not been evaluated. The present study examined whether preoperative supplements are beneficial in this group. In a randomised controlled trial, patients were assigned to receive 400 mL of oral supplement and dietary advice or dietary advice alone. Primary outcome was the number of post-operative complications. One hundred and twenty-five patients were recruited (59 randomised to the intervention group and 66 to the control group) and nine were excluded. In the intervention group, 24 (44%) patients had a complication compared to 26 (42%) in the control group (P = 0.780). In the intervention and control groups, there were eight (15%) and 16 (25%) surgical site infections, respectively (P = 0.140) and seven (13%) and 11 (17%) chest infections, respectively (P = 0.470). Subgroup analysis for hypothesis generation included 83 (71%) weight-losing patients, where there was a significant reduction in surgical site infections using the Buzby definition (P = 0.034), although this was not the case for the Centre for Disease Control definition (P = 0.052). There was no evidence that preoperative supplements were beneficial in reducing the number of complications, although there may be some benefit for surgical site infections in selected weight-losing preoperative patients.

Nutritional status of preoperative colorectal cancer patients

The present study aimed to determine the extent of malnutrition in preoperative colorectal cancer patients. Malnutrition has been shown to affect post-operative outcome, so it would be beneficial to identify those who are malnourished or who are at risk of becoming so preoperatively. We examine whether weight loss is related to the length of stay or changes in fat free mass. Patients were enrolled consecutively from outpatients 2-4 weeks prior to surgery. Assessments included body mass index, percentage weight loss, dynamometry, Malnutrition Universal Screening Tool, Subjective Global Assessment and bioelectrical impedance. Cancer staging and hospital length of stay were recorded. One hundred and thirty-two patients were eligible and 87 enrolled. Sixty-seven patients were weight losing and 20% had lost >10% of their usual body weight. Handgrip strength was lower in malnourished patients compared to those who had not lost weight (mean 19.4 and 27.3 kg, respectively, P = 0.013). Mean (SD) fat free mass in patients with a weight loss >10% was 39.7 (13.5) kg and, in those with <10% weight loss, was 51.9 (12.0) kg (P = 0.001). This difference was not demonstrated for fat. Over half of these patients had lost weight prior to surgery and one in five were malnourished. Body composition measurements demonstrated that malnourished patients had significantly less fat free mass compared to patients who were not clinically malnourished. Nutritional screening would be beneficial in this group preoperatively to identify weight-losing patients at an early stage in the care pathway when they initially enter the secondary care system.

Characterization of human skeletal muscle in weight-losing pancreatic cancer patients

9571 Background: Decreased body mass (cachexia) is a common cause of functional decline in pancreas carcinoma (PC) and other malignancies. The etiology is unknown. Characterization of human PC skeletal muscle, in regard to proteolysis and gene expression, compared to control muscle may reveal information about pathophysiology. Methods: Biopsies of rectus abdominus muscle were performed in weight-losing PC patients all stages (A) during cancer-related surgery and in cancer-free controls undergoing ventral hernia repair (B). Caspase-3, pAkt, and urinary 3-methylhistidine (u3-MH) were assessed by Western blot and high-performance liquid chromatography. Fat-free mass (FFM), body mass index (BMI), and time to progression were recorded. Muscle from five patients (median weight loss 21%) and five controls were analyzed for gene expression patterns using Affymetrix Human Genome U133 A 2.0 array chip. Two hundred differentially over- and under-expressed genes were examined in group A for potential association with cachexia. RT-PCR confirmation of six candidate genes was performed. Results: Thirty-eight patients were enrolled. Median weight loss in group A (N=27) was 14.5% (5% - 34%). No differences were noted between groups in caspase-3 and pAkt expression. Baseline u3-MH (p=0.86) and FFM (p= 0.28) did not differ; baseline BMI was lower in group A (p=0.04). BMI follow-up measurements (N=17) were significantly decreased (p=0.0005). In 65% patients, progressive disease was noted within median time of 3 months. RT-PCR established up-regulation of CHRNA1 and LMO7, but not GDF8. mRNA down-regulation for TRIM63, IGF-BP6, and MYH-1 was confirmed. Conclusions: Muscle proteolysis in human PC skeletal muscle was not demonstrated, perhaps due to unmeasurable proteolysis or use of non-informative endpoints. BMI decreased in group A with PD; further studies need tight control of BMI variables. New hypotheses about cachexia include neuromuscular junction dysfunction, as CHRNA1 has specific role in ion channel gating; this is disrupted in the paraneoplastic Eaton-Lambert syndrome. This is first study analyzing human muscle in weight-losing PC and proves symptom management multidisciplinary research is feasible in academic setting. Supported by American Cancer Society pilot grant. No significant financial relationships to disclose.

Defining and Classifying Cancer Cachexia: A Proposal by the SCRINIO Working Group

Although cancer cachexia is widely diffuse in the cancer patient population, there is no objective definition and classification of this syndrome. The purpose of this study is to propose a simple and quick classification that relies on the severity of the body weight loss and presence/absence of symptoms that are associated with cancer cachexia. The authors used a database of an ongoing multicenter prospective investigation on the screening of the nutrition risk of 1307 cancer outpatients from different (mainly Italian) university or scientific institutes or hospitals. The database included demographic, oncologic, clinical, and nutrition data. The patients were divided into 4 classes based on combinations of body weight loss (< 10%, precachexia; > or = 10%, cachexia) and the presence/absence of at least 1 symptom of anorexia, fatigue, or early satiation. The authors verified statistically whether these 4 classes were associated with the distribution of main clinical, nutrition, and oncologic variables, after adjustment for treatment status, by using the Cochrane-Mantel-Hanszel test for count data and ANOVA for continuous data. Moving from "asymptomatic precachexia" (class 1) to "symptomatic cachexia" (class 4), there were statistically significant trends (P < .0001) in the percentage of gastrointestinal vs nongastrointestinal tumors, severity of cancer stage, percentage of weight loss, number of symptoms per patient, Eastern Cooperative Oncology Group (ECOG) performance status, and nutritional risk score. The statistical analysis has validated the classification by identifying stages with different severity of cachexia. This classification could be adopted within a comprehensive oncologic approach to the weight-losing patients, until more specific diagnostic techniques are available in clinical practice.

Cancer cachexia: Measured and predicted resting energy expenditures for nutritional needs evaluation

Objective Cancer cachexia is associated with weight loss, poor nutritional status, and systemic inflammation. Accurate nutritional support for patients is calculated on resting energy expenditure (REE) measurement or prediction. The present study evaluated the agreement between measured and predicted REE (mREE and pREE, respectively) and the influence of acute phase response (APR) on REE. Methods Thirty-six patients with cancer were divided into weight-stable (WS; weight loss <2%) and weight-losing (WL; weight loss >5%) patients. Measured REE was measured by indirect calorimetry and adjusted for fat-free mass (FFM). The Bland-Altman approach was used to assess the agreement between mREE and pREE from the Harris-Benedict equations (HBE). Blood levels of C-reactive protein were assessed. Results There was no difference in mREE between groups (WS 1677 ± 273, WL 1521 ± 305) even when mREE was adjusted for FFM (WS 1609 ± 53, WL 1589 ± 53). In WL patients, FFM-adjusted REE correlated with blood C-reactive protein levels ( r = 0.471, P = 0.048). HBEs tend to underestimate REE in both groups. Conclusion WL and WS patients with cancer had similar REEs but were different in terms of APR. APR could contribute to weight loss through enhancing REE. In a clinical context, HBE was in poor agreement with mREE in both groups.

Apoptosis is present in skeletal muscle of cachectic gastro-intestinal cancer patients

Previous studies of our research group have shown that apoptosis is present in skeletal muscle of tumour-bearing animals subject to cachexia. For this reason we decided to investigate the apoptosis in skeletal muscle of cancer patients. In the present study, muscle biopsies from weight-losing patients with upper gastro-intestinal cancer showed a significant increase in muscle DNA fragmentation (three-fold), as compared with control subjects. The increase in DNA laddering was associated with an increase in poly(ADP-ribose) polymerase (PARP) cleavage (four-fold) as measured by western blotting. These two events indicate the presence of muscle apoptosis. These changes were associated with a decrease in MyoD protein content, suggesting important alterations in skeletal muscle physiology. The results presented therefore confirm that apoptosis is also present in human subjects undergoing cancer cachexia.

Evidence based practice guidelines for the nutritional management of cancer cachexia

The purpose of these guidelines is to provide dietitians in Australia with a user-friendly summary of the evidence to support the nutritional management of adult patients with cancer cachexia. This best available evidence is presented and used as a basis for providing recommendations about clinical practice. The clinical questions were as follows: How should patients be identified for referral to the dietitian in order to maximise nutritional intervention opportunities? How should nutritional status be assessed? What are the goals of nutrition intervention for patients with cancer cachexia? What is the nutrition prescription to achieve these goals? Should eicosapentaenoic acid be included in the prescription? What are effective methods of implementation to ensure positive outcomes? Does nutrition intervention improve outcomes in patients with cancer cachexia? This document is a general guide to appropriate practice to be followed only subject to the dietitian's judgement in each individual case. The guidelines are designed to provide information to assist decision-making and are based on the best information available at the date of compilation. The guidelines recommend intensive nutrition therapy. This has potential resource implications that may include additional staff, change to staff roles and increased use of high/protein energy supplements if they are considered. Therefore, in applying the guidelines these potential organisational and cost barriers need to be considered. These guidelines for practice are provided with the express understanding that they do not establish or specify particular standards of care, whether legal, medical or other.

Double-Blind, Placebo-Controlled, Randomized Study of Eicosapentaenoic Acid Diester in Patients With Cancer Cachexia

Eicosapentaenoic acid (EPA) has been proposed to have specific anticachectic effects. This trial compared EPA diethyl ester with placebo in cachectic cancer patients for effects on weight and lean body mass. Five hundred eighteen weight-losing patients with advanced gastrointestinal or lung cancer were studied in a multicenter, double-blind, placebo controlled trial. Patients were randomly assigned to receive a novel preparation of pure EPA at a dose of 2 g or 4 g daily or placebo (2g EPA, n = 175; 4 g EPA, n = 172; placebo, n = 171). Patients were assessed at 4 weeks and 8 weeks. The groups were well balanced at baseline. Mean weight loss at baseline was 18% (n = 518). Over the 8-week treatment period, both intention-to-treat analysis and per protocol analysis revealed no statistically significant improvements in survival, weight, or other nutritional variables. There was, however, a trend in favor of EPA with analysis of the primary end point, weight, at 8 weeks showing a borderline, nonsignificant treatment effect (P = .066). Relative to placebo, mean weight increased by 1.2 kg with 2 g EPA (95% CI, 0 kg to 2.3 kg) and by 0.3 kg with 4 g EPA (-0.9 kg to 1.5 kg). The results indicate no statistically significant benefit from single agent EPA in the treatment of cancer cachexia. Future studies should concentrate on other agents or combination regimens.

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 = 1500 kcal/d), and systemic inflammation (C-reactive protein > 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.

Branched-chain amino acids: the best compromise to achieve anabolism?

The anorexia-cachexia syndrome is highly prevalent in patients suffering from acute and chronic diseases, including cancer, chronic renal failure and liver cirrhosis. Once it has developed, it significantly influences the clinical course of the underlying disease, simultaneously impinging on patients' quality of life. Unfortunately, currently available therapeutic strategies do not appear to greatly impact on patients' morbidity, mortality and quality of life. More effective therapies are needed to promote appetite and food intake, to preserve lean body mass, and to ameliorate patients' psychological distress. Branched-chain amino acids are neutral amino acids with interesting and clinically relevant metabolic effects. Their potential role as antianorexia and anticachexia agents was proposed many years ago, but only recent experimental studies and clinical trials have tested their ability to stimulate food intake and counteract muscle wasting in anorectic, weight-losing patients. By interfering with brain serotonergic activity and by inhibiting the overexpression of critical muscular proteolytic pathways, branched-chain amino acids have been shown to induce beneficial metabolic and clinical effects under different pathological conditions. Based on the available data, branched-chain amino acids appear to exert significant antianorectic and anticachectic effects, and their supplementation may represent a viable intervention not only for patients suffering from chronic diseases, but also for those individuals at risk of sarcopenia due to age, immobility or prolonged bed rest, including trauma, orthopedic or neurologic patients.

Impact of a protein and energy dense nutritional supplement containing eicosapentaenoic acid on weight-losing patients with head and neck cancer

8112 Background: Patients with squamous cell cancer of the head and neck (HNSCCa) often lose weight. Under-nutrition is associated with increased postoperative complications and mortality (Nozoe, 2002). A protein and energy dense nutritional supplement (SUP) containing the omega-3 fatty acid eicosapentaenoic acid (EPA) can increase weight and lean body mass (LBM), and improve physical activity and quality of life in pancreatic cancer patients (Fearon et al, 2003; Moses et al, 2004). The purpose of this study was to determine the impact of pre- and peri-operative use of the SUP on weight-losing HNSCCa patients. Methods: Preoperatively, HNSCCa patients with at least 5% premorbid weight loss anticipating surgical resection with curative intent (+/- chemoradiation) were offered 2 cans of SUP (300 kcal, 16g protein, 1g EPA/can) daily beginning at least 2 weeks before surgery. Weight was measured at baseline, hospital admission, and discharge. LBM was measured using bioelectrical impedance at baseline and at ho...

Adiponectin and the systemic inflammatory response in weight-losing patients with non-small cell lung cancer

The aim of the present study was to examine the relationship between adiponectin and the systemic inflammatory response in weight-losing patients with non-small cell lung cancer (NSCLC). Measurement of anthropometry, acute phase proteins, interleukin-6, leptin (total and free) and adiponectin were carried out on healthy subjects ( n=13) and non-small cell lung cancer patients with weight loss ( n=20). The groups were age and sex matched. Compared with the controls the cancer group had a lower BMI ( p<0.01), mid-upper arm circumference ( p<0.001), triceps skinfold thickness ( p<0.05) and circulating concentrations of albumin ( p<0.001), haemoglobin ( p<0.05), free and total leptin ( p<0.05) and adiponectin ( p<0.01). In contrast, the cancer group had elevated circulating concentrations of interleukin-6 and C-reactive protein concentrations ( p<0.001). In the cancer group circulating adiponectin concentrations were significantly inversely correlated with both free ( r s =−0.675, p=0.001) and total leptin concentrations ( r s =−0.690, p=0.001). However, neither weight loss, interleukin-6 or C-reactive protein concentrations were correlated with either adiponectin, free or total leptin concentrations in the cancer group. These results suggest that adipokine production is normal and is unlikely to play a major role in the abnormal fat metabolism in weight-losing cancer patients.

Palliative nutritional intervention in addition to cyclooxygenase and erythropoietin treatment for patients with malignant disease: Effects on survival, metabolism, and function

The role of nutrition in the palliative treatment of patients with malignancy-related cachexia is unclear. The goal of the current study was to determine whether specialized, nutrition-focused patient care could improve integrated whole-body metabolism and functional outcome in unselected weight-losing patients with malignant disease who were receiving systemic antiinflammatory (cyclooxygenase [COX]-inhibitory) treatment along with erythropoietin (EPO) support. Three hundred nine patients with malignant disease who experienced progressive cachexia due to solid tumors (primarily gastrointestinal lesions) were randomized to receive a COX inhibitor (indomethacin, 50 mg twice daily) and EPO (15-40,000 units per week) along with specialized, nutrition-focused patient care (oral nutritional support and home total parenteral nutrition [TPN]) provided on a patient-by-patient basis to attenuate inflammation, prevent anemia, and improve nutritional status. Control patients received the same indomethacin and EPO doses that study patients received without the added nutritional support. All patients were treated and followed until death. Biochemical assays (blood, liver, kidney, and thyroid), nutritional state assessment (food intake and body composition), and exercise testing with simultaneous measurement of whole-body respiratory gas exchange before and during exercise were performed before the start of treatment and then at regular intervals during the treatment period (every 2-30 months after treatment initiation). Statistical analyses were performed on 'intention-to-treat' and 'as-treated' bases. Home TPN was provided to approximately 50% of the study patients without severe complications. Over the entire observation period, rhEPO prevented the development of anemia in both study patients and control patients. Intention-to-treat analysis revealed an improvement in energy balance for nutritionally supported patients (P < 0.03); no other significant differences in outcome between study patients and control patients were observed. As-treated analysis demonstrated that patients receiving nutrition experienced prolonged survival (P < 0.01), which was accompanied by improved energy balance (P < 0.001), increasing body fat (P < 0.05), and a greater maximum exercise capacity (P < 0.04). A trend toward increased metabolic efficiency at maximum exercise (P < 0.06) for study patients relative to control patients also was observed. The results of the current study strongly support that nutrition is a limiting factor influencing survival and that nutritional support protects integrated metabolism and metabolic function in patients with progressive cachexia secondary to malignant disease.