Mean Muscle Attenuation Research Articles

P: 26 The Modification of Quantity and Quality of Muscle Mass Improves the Cognitive Impairment After TIPS

BACKGROUND: Hepatic encephalopathy (HE) is the major complication of transjugular intrahepatic portosystemic shunt (TIPS). In cirrhotic patients, a correlation between sarcopenia and hepatic encephalopathy has been suggested. AIM: to evaluate the evolution of the skeletal muscle quantity and quality at CT scan and of the patients' cognitive impairment (both overt and minimal HE) before and after TIPS. PATIENTS AND METHODS: 27 cirrhotic patients submitted to TIPS were studied. The modification of Skeletal Muscle Index (SMI), muscle attenuation, HE and plasma ammonia were evaluated before and after a mean follow-up of 9.8 ± 4 months after TIPS. RESULTS: During the follow-up, the mean SMI and muscle attenuation increased significantly, although not uniformly in all patients. PHES (Psychometric Hepatic Encephalopathy Score) and ammonia improved significantly in the patients with amelioration in SMI >10% (n = 16) and not in those without (n = 11) (PHES: −1.6 ± 2 vs −4.8 ± 2.1; P = 0.0005; ammonia: 48.5 ± 28.7 vs 96 ± 31.5 μg/dl; P = 0.0004). Moreover, the prevalence of minimal HE (12.5% vs 73%, P = 0.001) as well as the number of episodes of overt HE during the follow-up were significantly reduced in the patients with improved SMI. MELD remained stable or worsened after TIPS and was not significantly different between the groups with or without SMI improvement. CONCLUSION: The amelioration of muscle wasting and HE independent of liver function observed after TIPS supports the causal relationship between muscle wasting and HE.

Prognostic role of body composition parameters in gastric/gastroesophageal junction cancer patients from the EXPAND trial

BackgroundBody fat and/or muscle composition influences prognosis in several cancer types. For advanced gastric and gastroesophageal junction cancer, we investigated which body composition parameters carry prognostic information beyond well‐established clinical parameters using robust model selection strategy such that parameters identified can be expected to generalize and to be reproducible beyond our particular data set. Then we modelled how differences in these parameters translate into survival outcomes.MethodsFat and muscle parameters were measured on baseline computed tomography scans in 761 patients with advanced gastric or gastroesophageal junction cancer from the phase III EXPAND trial, undergoing first‐line chemotherapy. Cox regression analysis for overall survival (OS) and progression‐free survival (PFS) included body composition parameters and clinical prognostic factors. All continuous variables were entered linearly into the model as there was no evidence of non‐linear prognostic impact. For transferability, the final model included only parameters that were picked by Bayesian information criterion model selection followed by bootstrap analysis to identify the most robust model.ResultsMuscle and fat parameters formed correlation clusters without relevant between‐cluster correlation. Mean muscle attenuation (MA) clusters with the fat parameters. In multivariate analysis, MA was prognostic for OS (P < 0.0001) but not for PFS, while skeletal muscle index was prognostic for PFS (P = 0.02) but not for OS. Worse performance status Eastern Cooperative Oncology Group (ECOG 1/0), younger age (on a linear scale), and the number of metastatic sites were strong negative clinical prognostic factors for both OS and PFS. MA remained in the model for OS (P = 0.0001) following Bayesian information criterion model selection in contrast to skeletal muscle index that remained prognostic for PFS (P = 0.009). Applying stricter criteria for transferability, MA represented the only prognostic body composition parameter for OS, selected in >80% of bootstrap replicates. Finally, Cox model‐derived survival curves indicated that large differences in MA translate into only moderate differences in expected OS in this cohort.ConclusionsAmong body composition parameters, only MA has robust prognostic impact for OS. Data suggest that treatment approaches targeting muscle quality are unlikely to prolong OS noticeably on their own in advanced gastric cancer patients, indicating that multimodal approaches should be pursued in the future.

Subscapularis structural integrity and function after arthroscopic Latarjet procedure at a minimum 2-year follow-up

Subscapularis function after arthroscopic Bankart repair has been widely studied. However, data regarding subscapularis performance after arthroscopic Latarjet procedures are lacking. This study aimed to evaluate subscapularis clinical and radiologic performance after arthroscopic Latarjet procedures. We included 40 patients who underwent arthroscopic Latarjet procedure with a minimum 2-year follow-up. Clinical evaluation included Western Ontario Shoulder Instability Index and Rowe scores, specific subscapularis isokinetic study, and lift-off tests. Contralateral measurements were used for comparison. Computed tomographic evaluation included graft consolidation, muscle dimensions, and degree of fatty atrophy, calculated as the mean muscle attenuation (MMA). There was a decrease of 8.3% of maximum internal rotation peak torque in the operated arm (P = .02). However, there was nosignificant differencein the agonist-antagonist ratio: 76.9% in the operated arm and 76% in the contralateral (P = .82). Lift-off strength test demonstrated a decrease in the first year but not at final follow-up (P = .38). There was a significant decrease in lift-off distance of 23% compared to the contralateral side (P < .001). Subscapularis MMA was diminished when compared to the infraspinatus/teres minor (P < .001) at the expense of its upper part (P = .03). Hyperlaxity and number of dislocation episodes were correlated to a lower MMA (P = .046 and P = .005). Arthroscopic Latarjet procedures providesatisfactory clinical results. There seems to be a diminished subscapularis MMA depending on its superior half. Hyperlaxity and number of previous dislocations were correlated to a lower MMA. Although there was a decrease in the maximum internal rotation peak torque, we did not find any differencein the agonist-antagonist ratio or in the final lift-off strength between sides.

Machine Learning for Automatic Paraspinous Muscle Area and Attenuation Measures on Low-Dose Chest CT Scans

To develop and evaluate an automated machine learning (ML) algorithm for segmenting the paraspinous muscles on chest computed tomography (CT) scans to evaluate for presence of sarcopenia. A convolutional neural network based on the U-Net architecture was trained to perform muscle segmentation on a dataset of 1875 single slice CT images and was tested on 209 CT images of participants in the National Lung Screening Trial. Low-dose, noncontrast CT examinations were obtained at 33 clinical sites, using scanners from four manufacturers. The study participants had a mean age of 71.6 years (range, 70-74 years). Ground truth was obtained by manually segmenting the left paraspinous muscle at the level of the T12 vertebra. Muscle cross-sectional area (CSA) and muscle attenuation (MA) were recorded. Comparison between the ML algorithm and ground truth measures of muscle CSA and MA were obtained using Dice similarity coefficients and Pearson correlations. Compared to ground truth segmentation, the ML algorithm achieved median (standard deviation) Dice scores of 0.94 (0.04) in the test set. Mean (SD) muscle CSA was 14.3 (3.6) cm2 for ground truth and 13.7 (3.5) cm2 for ML segmentation. Mean (SD) MA was 41.6 (7.6) Hounsfield units (HU) for ground truth and 43.5 (7.9) HU for ML segmentation. There was high correlation between ML algorithm and ground truth for muscle CSA (r2 = 0.86; p < 0.0001) and MA (r2 = 0.95; p < 0.0001). The ML algorithm for measurement of paraspinous muscles compared favorably to manual ground truth measurements in the NLST. The algorithm generalized well to a heterogeneous set of low-dose CT images and may be capable of automated quantification of muscle metrics to screen for sarcopenia on routine chest CT examinations.

Power of computed-tomography-defined sarcopenia for prediction of morbidity after pancreaticoduodenectomy

BackgroundThe goal of our study was to evaluate the current approach in prediction of postoperative major complications after pancreaticoduodenectomy (PD), especially symptomatic pancreatic fistula (POPF), using parameters derived from computed tomography (CT).MethodsPatients after PD were prospectively collected in a database of the local department of surgery and all patients with CT scans available were assessed in this study. CT parameters were measured at the level of the intervertebral disc L3/L4 and consisted of the areas of the visceral adipose tissue (AVAT), the diameters of the pancreatic parenchyma (DPP) and the pancreatic duct (DPD), the areas of ventral abdominal wall muscle (AMVEN), psoas muscle (AMPSO), paraspinal muscle (AMSPI), total muscle (AMTOT), as well as the mean muscle attenuation (MA) and skeletal muscle index (SMI). Mann-Whitney-U Test for two independent samples and binary logistic regression were used for statistical analysis.ResultsOne hundred thirty-nine patients (55 females, 84 males) were included. DPD was 2.9 mm (Range 0.7–10.7) on median and more narrow in patients with complications equal to or greater stadium IIIb (p < 0.04) and severe POPF (p < 0.01). DPP median value was 17 (6.9–37.9) mm and there was no significant difference regarding major complications or POPF. AVAT showed a median value of 127.5 (14.5–473.0) cm2 and was significantly larger in patients with POPF (p < 0.01), but not in cases of major complications (p < 0.06). AMPSO, AMSPI, AMVEN and AMTOT showed no significant differences between major complications and POPF. MA was both lower in groups with major complications (p < 0.01) and POPF (p < 0.01). SMI failed to differentiate between patients with or without major complications or POPF.ConclusionBesides the known factors visceral obesity and narrowness of the pancreatic duct, the mean muscle attenuation can easily be examined on routine preoperative CT scans and seems to be promising parameter to predict postoperative complications and POPF.

Comparison of body composition techniques in Portuguese patients with gastrointestinal cancer

Introduction: Anthropometric measures and bioelectrical impedance have been used in the past for body composition assessment of cancer patients. However, more specific and precise methodologies, such as CT imaging, are now available. So the purpose of this study was to compare different body composition techniques, using CT scan as golden standard. Materials and methods: Cross-sectional study with 100 patients with gastrointestinal cancer (GI) enrolled consecutively at diagnosis. Clinical data including disease site and stage were collected. Performance status was assessed with the Eastern Cooperative Oncology Group Performance Status scale. Nutritional assessment was conducted with anthropometric measures, namely weight, height, triceps skinfold, arm and waist circumference were recorded. Also, fat free mass, body fat, total body water, phase angle, as well as raw data as resistance and reactance were obtained with bioelectrical impedance analysis (BIA) (Bodystat 1500 MDD). Body composition was also assessed with Computed Tomography (CT), images were acquired at the 3rd lumbar vertebrae-L3, muscle and fat tissue cross sectional areas (cm2) and mean muscle attenuation (Hounsfield Units, HU) were recorded. Skeletal Muscular Index (SMI-cm2/height2) was calculated and gender and Body Mass Index (BMI) specific cut-offs for SMI were used to define sarcopenia [1]. This study was approved by the ethics committee of Hospital Beatriz Ângelo. Results: Sarcopenia prevalence was 32% (n = 32). Sarcopenic patients were older (p = 0.003) and had a worse performance status (p = 0.06). Sarcopenic patients had a higher mean weight loss (p = 0.05), and a lower mean BMI (p = 0.03) although 56% of them were overweight/obese. CT defined sarcopenia could not be detected by many commonly used anthropometric measures, since no differences between sarcopenic and non-sarcopenic patients were found for waist circumference, triceps skin fold, arm muscle and fat area. When sarcopenic and non-sarcopenic patients were compared according to body composition data from BIA, the only significant differences refer to higher mean body water (p = 0.04) and lower phase angle (p = 0.04) in sarcopenic patients. Considering CT imaging as the gold standard, total fat area correlated with BMI (r = 0.862, p < 0.001) and waist circumference (r = 0.852, p < 0.001); subcutaneous fat area with FM from BIA (r = 0.810, p < 0.001) and visceral fat area with waist circumference (r = 0.782, p < 0.001). Skeletal muscle area from CT imaging was correlated with fat free mass from BIA (r = 0.745, p < 0.001). However, in absolute values no agreement was found between estimated whole body skeletal muscle using CT and BIA. Either weak or non-significant correlations were mostly observed between muscle radiation attenuation and anthropometry/BIA. Discussion and conclusions: Although correlations between CT scan and anthropometry/BIA were found, body composition assessment with anthropometry and BIA may be insufficient to identify sarcopenia and fat infiltration of skeletal muscle tissue. Therefore CT scan analysis should be routinely used in the nutritional assessment of GI cancer patients.

The modification of quantity and quality of muscle mass improves the cognitive impairment after TIPS.

Hepatic encephalopathy (HE) is the major complication of transjugular intrahepatic portosystemic shunt (TIPS). In cirrhotic patients, a correlation between sarcopenia and HE has been suggested. To evaluate the evolution of the skeletal muscle quantity and quality at CT scan and of the patients' cognitive impairment (both overt and minimal HE) before and after TIPS. Twenty-seven cirrhotic patients submitted to TIPS were studied. The modification of Skeletal Muscle Index (SMI), muscle attenuation, HE and plasma ammonia were evaluated before and after a mean follow-up of 9.8±4months after TIPS. During the follow-up, the mean SMI and muscle attenuation increased significantly, although not uniformly in all patients. Psychometric Hepatic Encephalopathy Score (PHES) and ammonia improved significantly in the patients with amelioration in SMI >10% (n=16) and not in those without (n=11) (PHES: -1.6±2 vs -4.8±2.1; P=0.0005; ammonia: 48.5±28.7 vs 96±31.5μg/dL; P=0.0004). Moreover, the prevalence of minimal HE (12.5% vs 73%, P=0.001) as well as the number of episodes of overt HE during the follow-up were significantly reduced in the patients with improved SMI. Model for end-stage liver disease remained stable or worsened after TIPS and was not significantly different between the groups with or without SMI improvement. The amelioration of muscle wasting and HE independent of liver function observed after TIPS supports the causal relationship between muscle wasting and HE.

Sarcopenia is associated with postoperative complication after pancreaticoduodenectomy

Introduction: The sarcopenia which is skeletal muscle depletion has been reported to be associated with postoperative recurrence as well as postoperative complications. The aim of this study was to examine whether sarcopenia affects postoperative complications and cancer recurrence. Method: From January 2010 to December 2016, the data of 128 patients who underwent pancreaticoduodenectomy for pancreatic ductal adenocarcinoma, distal bile duct cancer, or ampulla of Vater cancer were consecutively collected. Sarcopenia was validated by lumbar skeletal muscle index, and mean muscle attenuation (Hounsfield units) by computed tomography (CT). The index was measured before surgery, within 1 month after surgery, and between 2 months and 8 months after surgery. The risk factors of postoperative complication and tumor recurrence were investigated. Result: The median age was 69 years (range, 23 to 95). The value obtained by dividing the measured muscle mass by BMI was associated with both postoperative general complications and severe complications in multivariate analysis (p = 0.008 and p = 0.033, respectively). However, the muscle mass index was not associated with clinically relevant pancreatic fistula (p = 0.253). The index measured between 2 months and 8 months after surgery was lower than that measured before surgery. However, the index was not associated with cancer recurrence or death in the survival analysis. Conclusion: The skeletal muscle index measured by CT image was associated with general complication but not pancreatic fistula or survival after pancreaticoduodenectomy.

Performance of CT-based low skeletal muscle index, low mean muscle attenuation, and bioelectric impedance derived low phase angle in the detection of an increased risk of nutrition related mortality

The aim of this study was to evaluate in a head to head comparison the performance of bioimpedance derived low phase angle (PA), CT-based low skeletal muscle index (SMI) and low mean muscle attenuation (MA), and Pandora Score (PS) to detect an increased nutrition related mortality in hospitalized patients. A total of 7736 patients were hospitalized in Dessau community hospital (Nov 11, 2016-Feb 05, 2017). In 227/7736 patients an abdominal CT scan was obtained and low values (below threshold) of skeletal muscle index (SMI) and mean muscle attenuation (MA) were obtained at L3 level using Slice-O-Matic. In 180/227 patients, malnutrition screening (NRS-2002≥3), determination of low PA (<5th percentile) and calculation of 30-day mortality risk (PS≥5%) were done within 6 days after the CT scan. PA was low in 116 (64%), SMI was low in 95 (53%), and MA was below threshold in 137 (77%) patients. Using hospital mortality (8.3%) as a gold standard, low SMI, low MA, or low PA showed high sensitivity (SMI 93.3%; MA 86.7%; PA 86.7%) and high negative predictive (NPV) values (SMI 98.9%; MA 95.3%; PA 96.9%) and improved specificity (NRS+SMI 65.5%; NRS+MA 50.3%; NRS+PA 50.3%) when combined with the criterion NRS≥3. Using hospital mortality as a gold standard, a PS≥36 (predicted mortality≥5%) showed a sensitivity of 73.3%, a specificity of 62.2% and an NPV of 96.4%. PS predicted mortality was ≥5% in 70 (39%) patients and was higher (median 5.2%; IQR: 2.8; 11.8 vs 1.7%; IQR: 1.0; 2.8; p<0.001) in patients with a low PA and this was also observed for low vs normal SMI (median 5.7%; IQR: 2.6; 11.1 vs 2.7%; IQR:1.4;5.5; p<0.001) but not for low vs normal MA (median 3.9%; IQR: 2.1; 8.8 vs 3.4%; IQR: 2.0; 8.1; ns). Determination of phase angle<5th percentile is a convenient non-invasive and inexpensive bedside method with high sensitivity and a high negative predictive value to detect patients at risk of nutrition related mortality with a performance comparable to CT derived skeletal muscle index or mean muscle attenuation.

Impact of Low Muscularity and Myosteatosis on Long-term Outcome After Curative Colorectal Cancer Surgery: A Propensity Score-Matched Analysis.

Muscle loss, characterized by reduced muscle mass (myopenia), and infiltration by intermuscular and intramuscular fat (myosteatosis), predicts a poor short-term prognosis in patients with colorectal cancer. However, little is known about the influence of myopenia and myosteatosis on long-term outcomes. The present study aimed to evaluate the prognostic influence of both myopenia and myosteatosis on long-term outcomes after curative colorectal cancer surgery. This is a retrospective analysis using a propensity score-matched analysis to reduce the possibility of selection bias. The study was conducted at a single institution. We performed a retrospective analysis of 211 consecutive patients with stage I to III colorectal cancer who underwent curative surgery between 2010 and 2011. CT scans were analyzed to calculate the lumbar skeletal muscle index and mean muscle attenuation using a SYNAPS VINCENT. The primary outcome measure was cancer-specific survival. Secondary end points included overall survival and disease-free survival. Of 211 patients, a total of 102 and 106 were matched for myopenia and myosteatosis analyses. The median follow-up was 57.6 months. Versus the nonmyopenia group, the myopenia group manifested a significantly shorter cancer-specific survival, overall survival, and disease-free survival. Significantly shorter cancer-specific survival and overall survival times were also identified for the myosteatosis versus the nonmyosteatosis group. Before matching, multivariate analyses identified both myopenia and myosteatosis as independent prognostic factors for cancer-specific survival (p = 0.04 and p < 0.01), overall survival (p = 0.03 and p < 0.01), and disease-free survival (p < 0.01 and p < 0.01). This study is limited by its retrospective, nonrandomized design. Myopenia and myosteatosis adversely affect long-term outcomes after curative colorectal cancer resection. See Video Abstract at http://links.lww.com/DCR/A463.

Progressive Sarcopenia in Patients With Colorectal Cancer Predicts Survival.

The purpose of this study was to evaluate the relationship between sarcopenia and overall and progression-free survival in patients with colorectal cancer. This study was retrospective and complied with HIPAA. Patients with colorectal cancer who underwent CT at the time of and 6-18 months after diagnosis were included. Patients were followed for at least 5 years after diagnosis. Skeletal muscle index (SMI) and mean muscle attenuation of the psoas and paraspinal muscles at the L4 level determined the degree of sarcopenia. Composite measurements combining psoas and paraspinal muscles (total muscle) were also obtained. Univariate and multivariate Cox proportional hazard analysis was performed to evaluate the association between survival and changes in SMI and changes in attenuation. Kaplan-Meier analysis was also performed. A total of 101 patients were included (mean age ± SD, 63.7 ± 13.7 years; 68 men, 33 women). The hazard ratios for overall survival were 2.27, 1.68, and 1.54 for changes in SMI of the psoas muscle, paraspinal muscle, and total muscle (all p < 0.05). The hazard ratios for overall survival were 1.14, 1.18, and 1.24 for changes in attenuation of the psoas muscle, paraspinal muscle, and total muscle, respectively (all p < 0.05). The hazard ratios for progression-free survival were 1.33, 1.41, and 1.23 for changes in SMI of the psoas muscle, paraspinal muscle, and total muscle (not statistically significant). The hazard ratios for progression-free survival were 1.10, 1.21, and 1.23 for changes in attenuation of the psoas muscle, paraspinal muscle, and total muscle, respectively (p < 0.05). Kaplan-Meier analysis showed significant differences in overall and progression-free survival based on sex-specific quartiles of muscle quantity and quality. Progressive sarcopenia after diagnosis of colorectal cancer has a significant negative prognostic association with overall and progression-free survival.

Skeletal muscle analyses: agreement between non‐contrast and contrast CT scan measurements of skeletal muscle area and mean muscle attenuation

Low skeletal muscle area (SMA) and muscle radiation attenuation (MRA) have been associated with poor prognosis in various patient populations. Both non-contrast and contrast CT scans are used to determine SMA and MRA. The effect of the use of a contrast agent on SMA and MRA is unknown. Therefore, we investigated agreement between these two scan options. SMA and MRA of 41 healthy individuals were analysed on a paired non-contrast and contrast single CT scan, and agreement between paired scan results was assessed with use of Bland-Altman plots, intraclass correlation coefficients (ICCs), standard error of measurements (SEM) and smallest detectable differences at a 95% confidence level (SDD95 ). Analyses were stratified by tube voltage. Difference in SMA between non-contrast and contrast scans made with a different tube voltage was 7·0±7·5cm2 ; for scans made with the same tube voltage this was 2·3±1·7cm2 . Agreement was excellent for both methods: ICC: 0·952, SEM: 7·2cm2 , SDD95 : 19·9cm2 and ICC: 0·997, SEM: 2·0cm2 , SDD95 : 5·6cm2 , respectively. MRA of scans made with a different tube voltage differed 1·3±11·3 HU, and agreement was poor (ICC: 0·207, SEM: 7·9 HU, SDD95 : 21·8 HU). For scans made with the same tube voltage the difference was 6·7±3·2 HU, and agreement was good (ICC: 0·682, SEM: 5·3 HU, SDD95 : 14·6 HU). In conclusion, SMA and MRA can be slightly influenced by the use of contrast agent. To minimise measurement error, image acquisition parameters of the scans should be similar.

Associations of adipose and muscle tissue parameters at colorectal cancer diagnosis with long-term health-related quality of life

PurposeIncreased visceral adiposity (visceral obesity) and muscle wasting (sarcopenia) at colorectal cancer (CRC) diagnosis, quantified by computed tomography (CT) image analysis, have been unfavorably associated with short-term clinical outcomes and survival, but associations with long-term health-related quality of life (HRQoL) have not been investigated. We studied associations of visceral adiposity, muscle fat infiltration, muscle mass, and sarcopenia at CRC diagnosis with HRQoL 2–10 years post-diagnosis.MethodsA cross-sectional study was conducted in 104 stage I‒III CRC survivors, diagnosed at Maastricht University Medical Center+, the Netherlands (2002–2010). Diagnostic CT images at the level of the third lumbar vertebra were analyzed to retrospectively determine visceral adipose tissue area (cm2); intermuscular adipose tissue area (cm2) and mean muscle attenuation (Hounsfield units) as measures of muscle fat infiltration; and skeletal muscle index (SMI, cm2/m2) as measure of muscle mass and for determining sarcopenia.ResultsParticipants showed a large variation in body composition parameters at CRC diagnosis with a mean visceral adipose tissue area of 136.1 cm2 (standard deviation: 93.4) and SMI of 47.8 cm2/m2 (7.2); 47% was classified as being viscerally obese, and 32% as sarcopenic. In multivariable linear regression models, associations of the body composition parameters with long-term global quality of life, physical, role and social functioning, disability, fatigue, and distress were not significant, and observed mean differences were below predefined minimal important differences.ConclusionsAlthough visceral obesity and sarcopenia are relatively common at CRC diagnosis, we found no significant associations of these parameters with long-term HRQoL in stage I–III CRC survivors.

Body composition of the host influences dendritic cell phenotype in patients treated for colorectal cancer.

Dendritic cells (DCs) are antigen-presenting cells that can acquire tumour antigens and initiate cytotoxic T cell reactions. Obesity has been proposed as a cause for tumours escaping immune surveillance, but few studies investigate the impact of other body composition parameters. We examined the relationship of DC phenotype with computer tomography (CT)-defined parameters in patients with colorectal cancer (CRC). DCs were identified within peripheral blood mononuclear cells by flow cytometry as HLA-DR positive and negative for markers of other cell lineages in 21 patients. Analysis of CT scans was used to calculate lumbar skeletal muscle index (LSMI) and mean muscle attenuation (MA). Positive correlation between the LSMI and expression of CD40 in all DCs (r = 0.45; p = 0.04) was demonstrated. The MA was positively correlated with scavenger receptor CD36 [all DCs (r = 0.60; p = 0.01) and myeloid DCs (r = 0.63; p < 0.01)]. However, the MA was negatively correlated with CCR7 expression in all DCs (r = -0.46, p = 0.03.) and with CD83 [all DCs (r = -0.63; p = 0.01) and myeloid DCs (r = -0.75; p < 0.01)]. There were no relationships between the fat indexes and the DC phenotype. These results highlight a direct relationship between muscle depletion and changes in stimulatory, migratory and fatty acid-processing potential of DC in patients with CRC.

Low Muscularity and Myosteatosis Is Related to the Host Systemic Inflammatory Response in Patients Undergoing Surgery for Colorectal Cancer.

We examined the relationships between computed tomography (CT)-defined skeletal muscle parameters and the systemic inflammatory response (SIR) in patients with operable primary colorectal cancer (CRC). Muscle depletion is characterized by a reduced muscle mass (myopenia) and increased infiltration by inter- and intramuscular fat (myosteatosis). It is recognized as a poor prognostic indicator in patients with cancer, but the underlying factors remain unclear. A total of 763 patients diagnosed with CRC undergoing elective surgical resection between 2006 and 2013 were included. Image analysis of CT scans was used to calculate Lumbar skeletal muscle index (LSMI), and mean muscle attenuation (MA). The SIR was quantified by the preoperative neutrophil to lymphocyte ratio (NLR) and albumin levels. Correlation and multivariate regression analysis was performed to identify independent relationships between patient SIR and muscle characteristics. Patients with NLR > 3 had significantly lower LSMI and lower MA than those with NLR < 3 [LSMI = 42.07 cmm vs 44.27 cmm (P = 0.002) and MA = 30.04 Hounsfield unit (HU) vs 28.36 HU (P = 0.016)]. Multivariate logistic regression analysis showed that high NLR [odds ratio (OR) = 1.78 (95% confidence interval [CI]: 1.29-2.45), P < 0.001] and low albumin [OR = 1.80 (95% CI: 1.17-2.74), P = 0.007] were independent predictors of reduced muscle mass. High NLR was significantly related with a low mean MA and hence myosteatosis [OR = 1.60 (95% CI: 1.03-2.49), P = 0.038]. These results highlight a direct association between myopenia, myosteatosis, and the host SIR in patients with operable CRC. A better understanding of factors that regulate muscle changes such as myopenia and myosteatosis may lead to the development of novel therapies that influence a more metabolically "healthy" skeletal muscle and potentially alter cancer outcomes.

Asymmetry in CT Scan Measures of Thigh Muscle 2 Months After Hip Fracture: The Baltimore Hip Studies.

Hip fracture is an important problem for older adults with significant functional consequences. After hip fracture, reduced muscle loading can result in muscle atrophy. We compared thigh muscle characteristics in the fractured leg to those in the nonfractured leg in participants from the Baltimore Hip Studies 7th cohort using computed tomography scan imaging. At 2 months postfracture, a single 10mm axial computed tomography scan was obtained at the midthigh level in 43 participants (23 men, 20 women) with a mean age of 79.9 years (range: 65-96 years), and thigh muscle cross-sectional area, cross-sectional area of intermuscular adipose tissue, and mean radiologic attenuation were measured. Total thigh muscle cross-sectional area was less on the side of the fracture by 9.46cm(2) (95% CI: 5.97cm(2), 12.95cm(2)) while the cross-sectional area of intermuscular adipose tissue was greater by 2.97cm(2) (95% CI: 1.94cm(2), 4.01cm(2)) on the fractured side. Mean muscle attenuation was lower on the side of the fracture by 3.66 Hounsfield Units (95% CI: 2.98 Hounsfield Units, 4.34 Hounsfield Units). The observed asymmetry is consistent with the effect of disuse and inflammation in the affected limb along with training effects in the unaffected limb due to the favoring of this leg with ambulation during the postfracture period.

Sarcopenia, intramuscular fat deposition, and visceral adiposity independently predict the outcomes of hepatocellular carcinoma

Obesity defined by body mass index (BMI) significantly increases the risk of hepatocellular carcinoma (HCC). In contrast, not only obesity but also underweight is associated with poor prognosis in patients with HCC. Differences in body composition rather than BMI were suggested to be true determinants of prognosis. However, this hypothesis has not been demonstrated conclusively. We measured skeletal muscle index (SMI), mean muscle attenuation (MA), visceral adipose tissue index, subcutaneous adipose tissue index, and visceral to subcutaneous adipose tissue area ratios (VSR) via computed tomography in a large-scale retrospective cohort of 1257 patients with different stages of HCC, and comprehensively analyzed the impact of body composition on the prognoses. Among five body composition components, low SMI (called sarcopenia), low MA (called intramuscular fat [IMF] deposition), and high VSR (called visceral adiposity) were significantly associated with mortality, independently of cancer stage or Child-Pugh class. A multivariate analysis revealed that sarcopenia (hazard ratio [HR], 1.52; 95% confidence interval [CI], 1.18-1.96; p=0.001), IMF deposition (HR, 1.34; 95% CI, 1.05-1.71; p=0.020), and visceral adiposity (HR, 1.35; 95% CI, 1.09-1.66; p=0.005) but not BMI were significant predictors of survival. The prevalence of poor prognostic body composition components was significantly higher in underweight and obese patients than in normal weight patients. Sarcopenia, IMF deposition, and visceral adiposity independently predict mortality in patients with HCC. Body composition rather than BMI is a major determinant of prognosis in patients with HCC.

Measurement of skeletal muscle radiation attenuation and basis of its biological variation

Skeletal muscle contains intramyocellular lipid droplets within the cytoplasm of myocytes as well as intermuscular adipocytes. These depots exhibit physiological and pathological variation which has been revealed with the advent of diagnostic imaging approaches: magnetic resonance (MR) imaging, MR spectroscopy and computed tomography (CT). CT uses computer-processed X-rays and is now being applied in muscle physiology research. The purpose of this review is to present CT methodologies and summarize factors that influence muscle radiation attenuation, a parameter which is inversely related to muscle fat content. Pre-defined radiation attenuation ranges are used to demarcate intermuscular adipose tissue [from −190 to −30 Hounsfield units (HU)] and muscle (−29 HU to +150 HU). Within the latter range, the mean muscle radiation attenuation [muscle (radio) density] is reported. Inconsistent criteria for the upper and lower HU cut-offs used to characterize muscle attenuation limit comparisons between investigations. This area of research would benefit from standardized criteria for reporting muscle attenuation. Available evidence suggests that muscle attenuation is plastic with physiological variation induced by the process of ageing, as well as by aerobic training, which probably reflects accumulation of lipids to fuel aerobic work. Pathological variation in muscle attenuation reflects excess fat deposition in the tissue and is observed in people with obesity, diabetes type II, myositis, osteoarthritis, spinal stenosis and cancer. A poor prognosis and different types of morbidity are predicted by the presence of reduced mean muscle attenuation values in patients with these conditions; however, the biological features of muscle with these characteristics require further investigation.

Age, Obesity, Sarcopenia, and Proximity to Death Explain Reduced Mean Muscle Attenuation in Patients with Advanced Cancer.

Cancer cachexia is characterized by skeletal muscle loss. A feature of muscle wasting, reduction in the mean muscle attenuation from computed tomography images is believed to reflect pathological infiltration of fat into muscle. It is a reported prognostic indicator in cancer patients. To develop an explanatory multivariate model of muscle attenuation of cancer patients incorporating age, sex, disease characteristics, body composition. Time to death ≤92 days was included in the model as the demarcation of end-stage disease. Multivariate general linear model regression analysis of total mean muscle attenuation and change in muscle attenuation. Regional cancer center (Alberta, Canada). Patients with gastrointestinal and respiratory tract cancers (mean age 64±11 years, 44% female). Total adipose tissue and skeletal muscle cross sectional area, and mean muscle attenuation at the 3rd lumbar vertebra were assessed from baseline computed tomography (n=1719), and a subset with repeated measures (n=246 patients with a total of 871 images). At baseline, muscle attenuation associated with total skeletal muscle (β 0.09; 95% CI 0.07 to 0.11; p<0.001) and adipose tissue (β -0.032; 95% CI -0.035 to -0.029; p<0.001) cross sectional areas, age (β -0.28; 95% CI -0.32 to -0.24; p<0.001), time to death ≤92 days (β -1.9; 95% CI -3.1 to -0.7; p=0.003) and male sex (β -2.3; 95% CI -3.5 to -1.1; p<0.001). Change in muscle attenuation over time associated with total adipose tissue cross sectional area (β -0.008; 95% CI -0.012 to -0.004; p<0.001) and time to death ≤92 days (β -1.6; 95% CI -3.0 to -0.2; p=0.03). The radiation attenuation of skeletal muscle is lowest in individuals who are older, less muscular, have a higher fat mass and are within 92 days of death. Men had lower muscle attenuation than women when controlled for other variables.

Cancer Cachexia in the Age of Obesity: Skeletal Muscle Depletion Is a Powerful Prognostic Factor, Independent of Body Mass Index

Emerging evidence suggests muscle depletion predicts survival of patients with cancer. At a cancer center in Alberta, Canada, consecutive patients with cancer (lung or GI; N = 1,473) were assessed at presentation for weight loss history, lumbar skeletal muscle index, and mean muscle attenuation (Hounsfield units) by computed tomography (CT). Univariate and multivariate analyses were conducted. Concordance (c) statistics were used to test predictive accuracy of survival models. Body mass index (BMI) distribution was 17% obese, 35% overweight, 36% normal weight, and 12% underweight. Patients in all BMI categories varied widely in weight loss, muscle index, and muscle attenuation. Thresholds defining associations between these three variables and survival were determined using optimal stratification. High weight loss, low muscle index, and low muscle attenuation were independently prognostic of survival. A survival model containing conventional covariates (cancer diagnosis, stage, age, performance status) gave a c statistic of 0.73 (95% CI, 0.67 to 0.79), whereas a model ignoring conventional variables and including only BMI, weight loss, muscle index, and muscle attenuation gave a c statistic of 0.92 (95% CI, 0.88 to 0.95; P < .001). Patients who possessed all three of these poor prognostic variables survived 8.4 months (95% CI, 6.5 to 10.3), regardless of whether they presented as obese, overweight, normal weight, or underweight, in contrast to patients who had none of these features, who survived 28.4 months (95% CI, 24.2 to 32.6; P < .001). CT images reveal otherwise occult muscle depletion. Patients with cancer who are cachexic by the conventional criterion (involuntary weight loss) and by two additional criteria (muscle depletion and low muscle attenuation) share a poor prognosis, regardless of overall body weight.