Sarcopenic obesity and myosteatosis are associated with higher mortality in patients with cirrhosis.

BACKGROUND AND AIMS: Obesity is frequently associated with cirrhosis, and cirrhotic patients may develop simultaneous loss of skeletal muscle and gain of adipose tissue, culminating in the condition of sarcopenic obesity. Additionally, muscle depletion is characterized by both a reduction in muscle size and increased proportion of muscular fat, termed myosteatosis. In this study, we aimed to establish the frequency and clinical significance of sarcopenia, sarcopenic obesity and myosteatosis in cirrhotic patients. METHODS: We analysed 678 patients with cirrhosis. Sarcopenia, sarcopenic obesity and myosteatosis were analysed by CT scan using the third lumbar vertebrae skeletal muscle and attenuation indexes, using previously validated gender-and body mass index-specific cutoffs. RESULTS: Patients were predominately men (n = 457, 67%), and cirrhosis aetiology was hepatitis C virus in 269 patients (40%), alcohol in 153 (23%), non-alcoholic steatohepatitis/cryptogenic in 96 (14%), autoimmune liver disease in 55 (8%), hepatitis B virus in 43 (6%), and others in 5 patients (1%). Sarcopenia was present in 292 (43%), 135 had sarcopenic obesity (20%) and 353 had myosteatosis (52%). Patients with sarcopenia (22 ± 3 vs. 95 ± 22 months, P < 0.001), sarcopenic obesity (22 ± 3 vs. 95 ± 22 months, P < 0.001), and myosteatosis (28 ± 5 vs. 95 ± 22 months, P < 0.001) had worse median survival than patients without muscular abnormalities. By multivariate Cox regression analysis, both sarcopenia [hazard ratio (HR) 2.00, 95% confidence interval (CI) 1.44-2.77, P < 0.001], and myosteatosis (HR 1.42, 95% CI 1.02-1.07, P = 0.04) were associated with mortality. CONCLUSIONS: Sarcopenia, sarcopenic obesity and myosteatosis are often present in patients with cirrhosis, and sarcopenia and myosteatosis are independently associated with a higher long-term mortality in cirrhosis.

Physical activity interests and preferences of cancer patients with brain metastases: a cross-sectional survey.

BACKGROUND: Physical activity has been shown to positively impact cancer-related fatigue, physical functioning and quality of life outcomes in early stage cancer patients, however its role at the end stage of cancer has yet to be determined. Brain metastases are amongst the most common neurological complications of advanced cancer, with significant deterioration in fatigue and quality of life. The purpose of the present study was to examine the physical activity interests and preferences of cancer patients with brain metastases initiating palliative whole brain radiotherapy. METHODS: Thirty-one patients aged 18 years or older, cognitively intact, diagnosed with brain metastases, and with Palliative Performance Scale scores of greater than 30%, were recruited from a multidisciplinary outpatient brain metastases clinic. An interviewer-administered survey was used to assess physical activity interests and preferences of participants who were embarking upon palliative whole brain radiotherapy. RESULTS: 87% (n = 27) of participants felt that physical activity was important, however there was limited interest in participating in a structured program at the onset of palliative whole brain radiotherapy. Lung cancer diagnosis was associated with being less interested in participating in a physical activity program, and feeling less able to participate in a physical activity program at the onset of palliative whole brain radiotherapy. CONCLUSIONS: Cancer patients with brain metastases demonstrate limited interest and varied preferences for physical activity during palliative whole brain radiotherapy. Additional pilot work with this patient population is needed before physical activity interventions can be tested in clinical research.

Inclusion of Sarcopenia Within MELD (MELD-Sarcopenia) and the Prediction of Mortality in Patients With Cirrhosis.

OBJECTIVES: Limitations of the Model for End-Stage Liver Disease (MELD) score include its failure to assess the nutritional and functional status of cirrhotic patients. Our objectives were to evaluate the impact of sarcopenia in cirrhosis and whether the inclusion of muscularity assessment within MELD could improve the prediction of mortality in patients with cirrhosis. METHODS: We included 669 cirrhotic patients who were consecutively evaluated for liver transplantation. Skeletal muscle index at the third lumbar vertebra (L3 SMI) was measured by computed tomography, and sarcopenia was defined using previously published gender and body mass index-specific cutoffs. Using Cox proportional hazards regression, a novel MELD-sarcopenia score was derived. RESULTS: Sarcopenia was present in 298 patients (45%); sarcopenic patients had shorter median survival than non-sarcopenic patients (20±3 vs. 95±24 months, P<0.001). By Cox regression analysis adjusted for age, gender, and hepatocellular carcinoma, both MELD (hazard ratio (HR) 1.08, 95% confidence interval (CI) 1.06-1.10, P<0.001), and the L3 SMI (HR 0.97, 95% CI 0.96-0.99, P<0.001) were associated with mortality. Overall, the c-statistics for 3-month mortality were 0.82 (95% CI 0.78-0.87) for MELD and 0.85 (95% CI 0.81-0.88) for MELD-sarcopenia (P=0.1). Corresponding figures for 1-year mortality were 0.73 (95% CI 0.69-0.77) and 0.77 (95% CI 0.73-0.80), respectively (P=0.03). The c-statistics for 3-month mortality in patients with MELD<15 (0.85 vs. 0.69, P=0.02) and refractory ascites (0.74 vs. 0.71, P=0.01) were significantly higher for MELD-sarcopenia compared with MELD. CONCLUSIONS: Modification of MELD to include sarcopenia is associated with improved prediction of mortality in patients with cirrhosis, primarily in patients with low MELD scores. External validation of this prognostic index in larger cohorts of cirrhotic patients is warranted.

Correlates of objectively measured sedentary behavior in cancer patients with brain metastases: an application of the theory of planned behavior.

OBJECTIVE: The aim of this study is to examine the demographic, medical, and social-cognitive correlates of objectively measured sedentary behavior in advanced cancer patients with brain metastases. METHODS: Advanced cancer patients diagnosed with brain metastases, aged 18 years or older, cognitively intact, and with palliative performance scale greater than 30%, were recruited from a Rapid Access Palliative Radiotherapy Program multidisciplinary brain metastases clinic. A cross-sectional survey interview assessed the theory of planned behavior variables and medical and demographic information. Participants wore activPAL™ (PAL Technologies Ltd, Glasgow, United Kingdom) accelerometers recording time spent supine, sitting, standing, and stepping during 7 days encompassing palliative whole brain radiotherapy treatments. RESULTS: Thirty-one patients were recruited. Correlates of median time spent supine or sitting in hours per day were instrumental attitude (i.e., perceived benefits) of physical activity (r = -0.42; p = 0.030) and affective attitude (i.e., perceived enjoyment) of physical activity (r = -0.43; p = 0.024). Moreover, participants who sat or were supine for greater than 20.7 h per day reported significantly lower instrumental attitude (M = 0.7; 95% CI = 0.0-1.4; p = 0.051) and affective attitude (M = 0.7; 95% CI = 0.0-1.4; p = 0.041). Finally, participants who were older than 60 years of age spent more time sitting or being supine. CONCLUSIONS: Instrumental attitude and affective attitude were the strongest correlates of objectively measured sedentary behavior. This information could inform intervention studies to increase physical activity in advanced cancer patients with brain metastases.

Associations between objectively measured physical activity and quality of life in cancer patients with brain metastases.

CONTEXT: Physical activity has demonstrated benefits for quality of life (QoL) and cancer-related fatigue earlier in the cancer trajectory; however, less is known regarding its role in patients with end-stage cancer. OBJECTIVES: The primary aim of this study was to examine the association between objectively measured physical activity and QoL in cancer patients with brain metastases. METHODS: Patients diagnosed with brain metastases, aged 18 years or older, cognitively intact, and with Palliative Performance Scale scores greater than 30%, were recruited from a multidisciplinary brain metastases clinic. A cross-sectional survey interview assessed self-reported QoL (McGill Quality of Life Questionnaire), self-reported physical function (Late-Life Function and Disability Instrument), and symptoms (Edmonton Symptom Assessment System). Participants wore activPAL™ (PAL Technologies, Ltd., Glasgow, UK) accelerometers recording triaxial movement for seven days during palliative whole brain radiotherapy. RESULTS: A total of 31 patients were recruited. Median survival was 171 days from time of study consent, with 90% (28 of 31) of deaths by two year follow-up. Participants who stood for 1.6 hours or more per day had better QoL (mean=1.0; 95% confidence interval [CI]=0.1 to 1.9; P=0.034). Participants who stood for 1.6 hours or more per day had better QoL (mean=1.0; 95% CI=0.1 to 1.9; P=0.034). Participants who sat or were supine for 20.7 hours or more per day had better advanced lower extremity functioning (mean=-6.1; 95% CI=-11.9 to -0.3; P=0.040) and total functioning (mean=-10.6; 95% CI=-21.1 to -0.04; P=0.049), but worse depression (mean=2.1; 95% CI=0.3 to 3.9; P=0.028), anxiety (mean=2.8; 95% CI=0.7 to 5.0; P=0.012), and feeling of well-being (mean=1.9; 95% CI=0.2 to 3.6; P=0.028). CONCLUSION: Sedentary behavior appears to be associated with better physical functioning but worse psychosocial functioning in cancer patients with brain metastases.

Severe muscle depletion predicts postoperative length of stay but is not associated with survival after liver transplantation.

Muscle depletion or sarcopenia is associated with increased mortality in patients with cirrhosis; how it affects mortality after liver transplantation requires further study. In this study, we aimed to establish whether sarcopenia predicts increased morbidity or mortality after liver transplantation. We analyzed 248 patients with cirrhosis who had a computed tomography (CT) scan including the third lumbar vertebra before liver transplantation. Data were recovered from medical charts, the skeletal muscle cross-sectional area was measured with CT, and sarcopenia was defined with previously published sex- and body mass index-specific cutoffs. One hundred sixty-nine patients (68%) were male, and the mean age at transplantation was 55 ± 1 years. The etiologies of cirrhosis were hepatitis C virus (51%), alcohol (19%), autoimmune liver diseases (15%), hepatitis B virus (8%), and other etiologies (7%). Sarcopenia was present in 112 patients (45%), and it was more frequent in males (P = 0.002), patients with ascites (P = 0.02), and patients with higher bilirubin levels (P = 0.05), creatinine levels (P = 0.02), international normalized ratios (P = 0.04), Child-Pugh scores (P = 0.002), and Model for End-Stage Liver Disease scores (P = 0.002). The median survival period after liver transplantation was 117 ± 17 months for sarcopenic patients and 146 ± 20 months for nonsarcopenic patients (P = 0.4). Sarcopenic patients had longer hospital stays (40 ± 4 versus 25 ± 3 days; P = 0.005) and a higher frequency of bacterial infections within the first 90 days after liver transplantation (26% versus 15%, P = 0.04) in comparison with nonsarcopenic patients. In conclusion, sarcopenia is one of the most common complications in patients with cirrhosis and is predictive of longer hospital stays and a higher risk of perioperative bacterial infections after liver transplantation, but it is not associated with increased mortality.

Sarcopenia as a prognostic index of nutritional status in concurrent cirrhosis and hepatocellular carcinoma.

BACKGROUND AND AIMS: Abnormal body composition such as severe skeletal muscle depletion or sarcopenia has emerged as an independent predictor of clinical outcomes in a variety of clinical conditions. This study is the first study to report the frequency and prognostic significance of sarcopenia as a marker of nutritional status in patients with hepatocellular carcinoma (HCC). METHODS: We analyzed 116 patients with HCC who were consecutively evaluated for liver transplant. Skeletal muscle cross-sectional area was measured by CT. Sarcopenia was defined using previously established cutpoints. RESULTS: Ninety-eight patients were males (85%), and the mean age was 58±6 years. Sarcopenia was present in 35 patients (30%). By univariate Cox analysis, male sex (HR, 3.84; P=0.02), lumbar skeletal muscle index (HR, 0.97; P=0.04), INR (HR, 8.18; P<0.001), MELD score (HR, 1.19; P<0.001), Child-Pugh (HR, 3.95; P<0.001), serum sodium (HR, 0.84; P<0.001), TNM stage (HR, 2.59; P<0.001), treatment type (HR, 0.53; P<0.001), and sarcopenia (HR, 2.27; P=0.004) were associated with increased risks of mortality. By multivariate Cox regression analysis, only MELD score (HR, 1.08; P=0.04), Child-Pugh (HR, 2.14; P=0.005), sodium (HR, 0.89; P=0.01), TNM stage (HR, 1.92; P<0.001), and sarcopenia (HR, 2.04; P=0.02) were independently associated with mortality. Median survival for sarcopenic patients was 16±6 versus 28±3 months in nonsarcopenic (P=0.003). CONCLUSIONS: Sarcopenia is present in almost one third of patients with HCC, and constitutes a strong and independent risk factor for mortality. Our results highlight the importance of body composition assessment in clinical practice.

The Edmonton Symptom Assessment System, a proposed tool for distress screening in cancer patients: development and refinement.

OBJECTIVE: The Edmonton Symptom Assessment System (ESAS) has been proposed as one element of a distress screening strategy in cancer patients. It consists of 11-point numerical rating scales for self-report of nine common symptoms of cancer, with a 10th scale for a patient-specific symptom. The ESAS has undergone widespread adoption internationally for clinical, research and administrative purposes. Despite its rapid uptake, validity evidence has lagged behind, and concerns have been raised about feasibility and usefulness. The objective of this paper is to provide a synthesis of a program of research focusing on the psychometric properties of the ESAS. METHODS: We describe and discuss a series of three ESAS studies undertaken by our group: (i) a review of ESAS validation studies (1991-2006); (ii) a think-aloud study conducted in 20 advanced cancer patients; and (iii) a prospective multicenter study conducted in 160 patients in different palliative care settings, comparing the ESAS with a revised version (ESAS-r). RESULTS: The review identified 13 articles focusing on gathering reliability and/or validity evidence; the need to standardize the ESAS and conduct further validation research was apparent. The think-aloud study elucidated the complex cognitive processes by which patients arrive at symptom ratings and areas of potential difficulty in understanding and completing the ESAS. The multicenter study demonstrated that the ESAS-r was significantly easier for patients to understand. CONCLUSIONS: Overall, our findings support consideration of the ESAS and its successor, the ESAS-r, for use in distress screening in cancer patients. Areas for future research will be presented. Copyright © 2011 John Wiley & Sons, Ltd.

A multicenter study comparing two numerical versions of the Edmonton Symptom Assessment System in palliative care patients.

CONTEXT: The Edmonton Symptom Assessment System (ESAS) is a widely used, self-report symptom intensity tool for assessing nine common symptoms in palliative care, with ratings ranging from 0 (none, best) to 10 (worst). Based on a "think-aloud" study of 20 advanced cancer patients, the ESAS was revised (ESAS-r). OBJECTIVES: To compare the consistency of patients' symptom ratings and obtain patient perspectives regarding ease of understanding and completion between the ESAS and ESAS-r. METHODS: Cognitively intact patients (n=160) were recruited from eight palliative care sites in Canada and Switzerland, using cross-sectional sampling (20 per site). Consenting patients completed the ESAS, ESAS-r, and a structured interview. Intraclass correlation coefficients (ICCs) were calculated to assess rating consistency. RESULTS: In total, 1046 patients were screened. One hundred sixty were enrolled and evaluable (female 51%, median age 61 [range 34-92], lung cancer 26%, gastrointestinal cancer 22%). Mean ESAS scores ranged from 1.2 (nausea, standard deviation [SD] 2.1) to 4.3 (appetite, SD 3.3). ICCs ranged from 0.65 to 0.83, with lowest scores (<0.8) for drowsiness, appetite, and well-being. Although most patients rated both versions as very easy or easy to understand and complete, the ESAS-r was significantly easier to understand than the ESAS (P=0.008). Significantly, more patients preferred the ESAS-r (39%) than the ESAS (14%, P<0.001) because of its definitions, clarity, and format. CONCLUSION: The ESAS-r retains core elements of the ESAS, with improved interpretation and clarity of symptom intensity assessment. It represents the next generation of ESAS development, with further validation recommended for drowsiness, appetite, and well-being.

The Edmonton symptom assessment system--what do patients think?

GOALS OF WORK: The Edmonton Symptom Assessment System (ESAS) is a tool for self-reporting of symptom intensity, initially developed for advanced cancer patients. It consists of numerical rating scales for nine common symptoms, with the option of adding a tenth. Despite its widespread use in palliative care, few studies have focused on its psychometric properties, with none involving patient perspectives. The purpose of this study was to gather validity evidence for the ESAS, by examining patients' cognitive processes while completing the ESAS, understanding of terminology and numerical ratings, and opinions of the ESAS as a self-reporting tool. MATERIALS AND METHODS: English-speaking advanced cancer patients, referred to a Pain and Symptom Control Consultation Service in a cancer centre, were recruited. Using a qualitative "think aloud" study design, patients completed the ESAS independently while being prompted to verbalize their thoughts. They then answered a structured questionnaire to elicit their opinions of the ESAS. Transcripts of audio-taped sessions were coded and analyzed. MAIN RESULTS: Twenty patients were evaluable. Symptom ratings were influenced by current symptom profiles, temporal changes, symptom experience history and individual perceptions. Symptom interpretation and numerical rating assignments varied. Difficult terminology included tiredness versus drowsiness, depression, anxiety, appetite, and well-being. Most patients agreed with the item order and thought that the ESAS was easy to complete, with a health care professional present. Patients expressed a need to emphasize the timeframe as "now". CONCLUSION: Modification of the tool and administration process may be warranted, but further study in other populations is needed.

The Edmonton Symptom Assessment System: a 15-year retrospective review of validation studies (1991--2006).

INTRODUCTION: The purpose of this review was to identify and critique validation studies focusing on the Edmonton Symptom Assessment System (ESAS), a commonly used symptom assessment tool for advanced cancer and palliative patients. METHODS: Using a comprehensive literature search, the authors identified and screened 87 publications. Thirteen articles were selected for in-depth review, based on the following inclusion criteria: psychometric studies with a primary focus on the ESAS, 1991--2006 publication dates and peer-reviewed English language publications. RESULTS: Most studies involved cancer patients (n = 11). The ESAS format varied across studies, in terms of scale format, item number, item selection and language. Studies focused on gathering reliability estimates (n = 8), content validity evidence (n = 1), concurrent validity evidence (n = 5), predictive validity evidence (n = 1), and sensitivity and/or specificity (n = 3). None of these studies involved patients' perspectives as a source of validity evidence. DISCUSSION: The use of varying instrument formats and limited psychometric evidence support the need for further ESAS validation studies, including the involvement of patients.