Depletion Of Skeletal Muscle Mass Research Articles

Cancer Cachexia: Underlying Mechanisms and Potential Therapeutic Interventions.

Cancer cachexia, a multifactorial metabolic syndrome developed during malignant tumor growth, is characterized by an accelerated loss of body weight accompanied by the depletion of skeletal muscle mass. This debilitating condition is associated with muscle degradation, impaired immune function, reduced functional capacity, compromised quality of life, and diminished survival in cancer patients. Despite the lack of the known capability of fully reversing or ameliorating this condition, ongoing research is shedding light on promising preclinical approaches that target the disrupted mechanisms in the pathophysiology of cancer cachexia. This comprehensive review delves into critical aspects of cancer cachexia, including its underlying pathophysiological mechanisms, preclinical models for studying the progression of cancer cachexia, methods for clinical assessment, relevant biomarkers, and potential therapeutic strategies. These discussions collectively aim to contribute to the evolving foundation for effective, multifaceted counteractive strategies against this challenging condition.

Preoperative CT-Based Skeletal Muscle Mass Depletion and Outcomes after Total Laryngectomy.

To assess the role of preoperative CT-based skeletal muscle mass depletion on postoperative clinical outcomes and survival in patients who underwent total laryngectomy for cancer. Patients operated on between January 2011 and March 2020 were retrospectively included. Skeletal muscle area and intra- and inter-muscular fat accumulation were measured at the third lumbar vertebral level on preoperative CT scans. Skeletal muscle mass depletion was defined based on pre-established cut-off values. Their association with postoperative morbidity, length of stay (LOS), costs, and survival was assessed. A total of 84 patients were included, of which 37 (44%) had preoperative skeletal muscle mass depletion. The rate of postoperative fistula (23% vs. 35%, p = 0.348), cutaneous cervical dehiscence (17% vs. 11%, p = 0.629), superficial incisional surgical site infections (SSI) (12% vs. 10%, p = 1.000), and unplanned reoperation (38% vs. 37%, p = 1.000) were comparable between the two patient groups. No difference in median LOS was observed (41 vs. 33 days, p = 0.295), nor in treatment costs (119,976 vs. 109,402 CHF, p = 0.585). The median overall survival was comparable between the two groups (3.43 vs. 4.95 years, p = 0.09). Skeletal muscle mass depletion alone had no significant impact on postoperative clinical outcomes or survival.

Influence of Lower Limb Ischemia on Skeletal Muscle Mass Depletion in Patients with Peripheral Artery Disease

The aim of the study was to determine the change in skeletal muscle mass over time by bioelectrical impedance analysis (BIA) in patients with peripheral artery disease (PAD). Patients with symptomatic PAD visiting Tokyo Medical University Hospital between January 2018 and October 2020 were retrospectively analyzed. PAD was diagnosed based on ankle brachial pressure index (ABI)<0.9 with either leg and confirmed by duplex scan and/or computed tomography angiography as needed. Patients undergoing endovascular treatment, surgery, or supervised exercise therapy were excluded before and during the study period. Skeletal muscle mass of the extremities was measured using BIA. The sum of skeletal muscle masses in the arms and legs was calculated as skeletal muscle mass index (SMI). Patients were scheduled to undergo BIA at an interval of 1year. Of 119 patients, 72 patients were included in the study. All patients were ambulatory and had symptoms of intermittent claudication (Fontaine's stage II). SMI significantly decreased from 6.98±1.30 at baseline to 6.83±1.29 at 1-year follow-up. Individual skeletal muscle mass of the ischemic leg was significantly reduced after 1year, but not in the nonischemic leg. A decrease in SMI (defined as SMI ≥0.1kg/m2 per year) was independently associated with low ABI. The optimal cut-off value of ABI for the decrease in SMI was 0.72. These results suggest that lower limb ischemia due to PAD, especially if ABI is<0.72 or less, may result in a decrease in skeletal muscle mass that affects health and physical function.

Low appendicular skeletal muscle mass index is associated with the anthropometric variables of post-menopausal women

BackgroundSkeletal muscle mass is a central component of body composition and its decline is enhanced during aging. We verified the association between the appendicular skeletal muscle mass index (ASMI) with the anthropometric variables, biochemical variables, and lifestyle of postmenopausal women.MethodsCross-sectional observational study conducted with postmenopausal women. Sociodemographic, clinical, lifestyle, physical activity level, biochemical, and anthropometric markers were collected. Body composition was assessed by dual-energy densitometry. Multivariate logistic regression analysis was applied.ResultsOne hundred fourteen women aged in average 66.0 ± 5.8 years were evaluated. There was a significant association between ASMI and age (p = 0.004), body mass (p < 0.001), body mass index (BMI) (p < 0.001), adductor pollicis muscle thickness (APMT) (p < 0.001), plasma calcium levels (p = 0.003), calf circumference (CC), and waist circumference (WC) (p < 0.001 for both). Adjusted regression analyses revealed the influence of BMI, CC, and APMT in the 1st tertile of ASMI (p < 0.05), BMI and CC in the 2rd tertile of ASMI.ConclusionsASMI was associated with BMI and muscle mass reserve indicators such as CC and DAPMT. In clinical practice, this indicates that simple, low-cost measures with good applicability can be used to predict and track the risk of depletion of skeletal muscle mass and consequent sarcopenia.

Association between preoperative skeletal muscle mass depletion and poor relapse-free survival in patients with gastrointestinal stromal tumors after complete resection

ObjectivesThe aim of this study was to investigate the predictive effects of skeletal muscle mass (SMM) depletion on relapse risk in patients who had undergone complete surgical resection for primary resectable gastrointestinal stromal tumors (GISTs). MethodsThis retrospective study comprised 445 enrolled patients with primary resectable GISTs who had undergone surgical treatment between January 2013 and January 2021. The lumbar skeletal muscle index (SMI) was assessed using abdominal computed tomography images taken within 7 d preoperatively. Univariate and multivariate Cox regression analyses were performed to identify independent risk factors for nomogram construction. Predictive accuracy and discriminative ability were measured using the concordance index (C-index). ResultsThree- and 5-y relapse-free survival (RFS) rates for patients in the low SMI group were significantly worse than those in the high SMI group (81.3 and 75.4% versus 92.3 and 91.6%, respectively; P < 0.001). In stratification analysis using modified National Institutes of Health criteria, high-risk patients with low SMI showed significantly shorter RFS (P = 0.001). Multivariate analysis indicated that tumor size, tumor location, mitotic rates, the platelet-to-lymphocyte ratio, the prognostic nutritional index, and SMM depletion were independent prognostic factors for RFS (P < 0.05). These six variables were selected for nomogram construction, which showed superior discrimination with a C-index of 0.82. ConclusionsThere was a significant association between preoperative SMM depletion and a high risk for relapse in patients who had undergone complete resection for primary resectable GISTs, especially in patients with high-risk GIST. Our simple, practical, novel nomogram intuitively predicted RFS in these patients.

Skeletal Muscle Depletion and Major Postoperative Complications in Locally-Advanced Head and Neck Cancer: A Comparison between Ultrasound of Rectus Femoris Muscle and Neck Cross-Sectional Imaging.

Simple SummarySkeletal muscle mass (SMM) depletion is gaining popularity as independent predictor of postoperative complications in many surgical scenarios, even in the field of head and neck oncology. In this study, we demonstrate the value of ultrasound scans of the rectus femoris muscle together with the neck CT/MRI at C3 level in terms of estimation of SMM (through muscle cross sectional area), the identification of sarcopenic patients and as a predictor of major surgical morbidity in a cohort of locally-advanced head and neck cancer patients submitted to surgical treatment. This provides important tools for the on-going re-assessment of patients with regards to any pre-habilitation strategy aimed at reducing postoperative complications.Skeletal muscle mass (SMM) depletion has been validated in many surgical fields as independent predictor of complications through cross-sectional imaging. We evaluated SMM depletion in a stage III-IV head and neck cancer cohort, comparing the accuracy of CT/MRI at C3 level with ultrasound (US) of rectus femoris muscle (RF) in terms of prediction of major complications. Patients submitted to surgery were recruited from 2016 to 2021. SMM was estimated on CT/MRI by calculating the sum of the cross-sectional area (CSA) of the sternocleidomastoid and paravertebral muscles at C3 level and its height-indexed value (cervical skeletal muscle index, CSMI) and on US by computing the CSA of RF. Specific thresholds were defined for both US and CT/MRI according to ROC curve in terms of best prediction of 30-day major complications to detect sarcopenic subjects (40–53%). Sixty-five patients completed the study. At univariate analysis, major complications were associated to lower RF CSA, lower CSA at C3 level and lower CSMI, together with previous radiotherapy, higher ASA score and higher modified frailty index (mFI). At multivariate analysis RF CSA (OR 7.07, p = 0.004), CSA at C3 level (OR 6.74, p = 0.005) and CSMI (OR 4.02, p = 0.025) were confirmed as independent predictors in three different models including radiotherapy, ASA score and mFI. This analysis proved the value of SMM depletion as predictor of major complications in a head and neck cancer cohort, either defined on cross-sectional imaging at C3 or on US of RF.

Association between Sarcopenia and Omega-3 Polyunsaturated Fatty Acid in Patients with Hepatocellular Carcinoma.

Introduction: This study aimed to validate whether preoperative sarcopenia can predict long-term outcomes in patients with hepatocellular carcinoma (HCC) and identify the associations between sarcopenia and polyunsaturated fatty acids (PUFAs). Methods: This large, retrospective study included 353 patients who underwent hepatic resection for HCC and preoperative computed tomography scans. Skeletal muscle mass was measured at the third lumbar vertebrae. The cutoff value for sarcopenia followed the Japan Society of Hepatology’s assessment criteria for sarcopenia. Results: Ninety-three patients (26.3%) with preoperative sarcopenia were enrolled. These patients had a significantly lower body mass index (p < 0.0001) and serum albumin level (p = 0.0070) as well as a higher rate of advanced-stage cancer (p = 0.0062) than those without sarcopenia. Patients with sarcopenia had significantly shorter overall survival than the other patients before (p = 0.0001) and after (p = 0.0415) propensity score matching. The sarcopenia group was significantly associated with low levels of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), which were categorized based on omega-3 PUFAs, compared with those in the non-sarcopenia group (p = 0.0030 and p = 0.0135). Conclusions: We demonstrated an association between sarcopenia and the long-term prognosis in patients with HCC. Low EPA and DHA levels were associated with preoperative sarcopenia. Further prospective studies are needed to investigate whether nutritional support using omega-3 PUFAs can prevent and manage skeletal muscle mass depletion.

Defining reference values for low skeletal muscle index at the L3 vertebra level based on computed tomography in healthy adults: A multicentre study

Skeletal muscle mass loss is an important aspect of malnutrition and is closely related to adverse clinical outcomes. Computed tomography (CT) is the gold standard for analysing muscle mass, and the skeletal muscle index at the third lumbar vertebra (L3-SMI), measured using CT, is an important indicator to evaluate total skeletal tissue. The aims of this study were to establish reference values for low L3-SMI in Northern China, and to investigate the correlation between L3-SMI and age, and the correlation between L3-SMI and body mass index (BMI). This was a multicentre, retrospective, cross-sectional study. A search of abdominal CT imaging reports, using specific keywords, was conducted in four representative cities in northern China, from January 2016 to March 2021. Transverse CT images at the level of the third lumbar vertebra (L3) were identified, exported from the Radiology Information System, and measured using the analysis software SliceOmatic. Statistical analyses were performed using SPSS 24.0, and significance level was set at p<0.05. Mean, standard deviations (SD) and percentiles (p5, p10, p25, p50, p75, p90, p95) were used to describe the distribution of L3-SMI in the study population. Low skeletal muscle index was defined as a 5% percentile, or two standard deviations below the mean value of younger healthy individuals (age 20-39 years). The study included 1787 healthy individuals, with a median age of 45 (25) years (range 20-88 years), and a median BMI of 23.1 (4.1) kg/m2 (range 18.5-38.7kg/m2). Among them, 700 healthy individuals (39.1%) were aged 20-39 years. L3-SMI had a negative linear correlation with age, and a positive linear correlation with BMI. The L3-SMI reference values used to define low skeletal muscle mass loss in the Northern Chinese population, using the 5% percentile, were 40.2cm2/m2 in men, and 31.6cm2/m2 in women. Using the mean minus two standard deviations protocol, the reference values were 37.9cm2/m2 and 28.6cm2/m2 in men and women, respectively. This study analysed the human body composition of 1787 healthy people in four cities in northern China, using CT, and established diagnostic thresholds of skeletal muscle mass depletion based on 700 younger healthy adults, using the 5% percentile and mean-2SD methods. These reference values can be used to diagnose malnutrition in patients and may aide clinicians in predicting prognosis and improving nutritional therapy. Further research is warranted to determine the prognostic role of reference values against clinical outcomes in different disease populations.

Depletion of skeletal muscle mass adversely affects long-term outcomes for men undergoing gastrectomy for gastric cancer.

BackgroundAlthough low skeletal muscle mass has an adverse impact on the treatment outcomes of cancer patients, whether the relationship between preoperative skeletal muscle mass and gastrectomy outcomes in gastric cancer (GC) differs between men and women is unclear. The study aimed to clarify this relationship based on gender.MethodsBetween January 2007 and December 2015, 1054 patients who underwent gastrectomy for GC at Osaka City General Hospital were enrolled in this study. We evaluated sarcopenia by the skeletal muscle index (SMI), which was measured by computed tomography (CT) using areas of muscle in the third lumbar vertebral body (L3). Male and female patients were each divided into two groups (low skeletal muscle and high skeletal muscle).ResultsThe SMI emerged as an independent predictor of 5-year overall survival (OS) in male GC patients (Hazard ratio 2.51; 95% confidence interval (CI) 1.73–3.63, p < 0.001) based on multivariate analysis. However, this index was not an independent predictive determinant of 5-year cancer-specific survival (CSS). The SMI was not an independent predictor of either OS or CSS in female GC patients. The incidence of leakage and major complication (Clavien Dindo grade ≧ 3) did not differ significantly across groups.ConclusionsPreoperative skeletal muscle mass is a valuable prognostic predictor of OS in male GC patients.

Evaluation of techniques used to assess skeletal muscle quantity in patients with cirrhosis.

Loss of skeletal muscle mass is a well-recognised complication of cirrhosis. Bedside methods to assess skeletal muscle mass including anthropometrics and bioelectrical impedance analysis (BIA) are negatively impacted by fluid overload in advanced cirrhosis and thus there is a need to identify alternatives. There is a paucity of data on the accuracy of commonly used radiological methods such as dual X-ray absorptiometry (DXA) to assess appendicular lean mass (ALM), and computed tomography (CT) skeletal muscle area in patients with cirrhosis. The aim of this study was to evaluate the relationships and agreement of several skeletal muscle mass estimation methods compared to a reference model in patients with cirrhosis. A cross-sectional, single centre study was performed by prospectively recruiting patients with cirrhosis referred to the Queensland Liver Transplant Service. Patients underwent assessment of skeletal muscle mass using bedside techniques (mid-upper arm muscle circumference (MUAMC), bioelectrical impedance spectroscopy (BIS), ultrasound muscle thickness (USMT)) and radiological methods (DXA ALM, CT skeletal muscle area). These were compared to a reference measurement of body cell mass derived from a multi-compartment model using isotope dilution tests and DXA. Forty-two patients (age 56 years, interquartile range 48-60, 86% male) were recruited. Bedside skeletal muscle mass estimation techniques were strongly correlated to the body cell mass reference, with BIS estimation having the strongest correlation coefficients (r=0.78-0.79; P<0.01). A novel technique measuring USMT offered no advantage over traditional bedside techniques. Of the radiological methods, DXA ALM had the strongest correlation coefficient (r=0.781; P<0.01). Weaker correlation coefficients were observed in patients with ascites, except when using the MUAMC. Bland-Altman analysis of BIS body composition estimates demonstrated significant systematic biases and large limits of agreement compared to reference values. These results confirm the difficulties in assessing skeletal muscle mass in patients with cirrhosis, particularly in those with ascites. DXA ALM and BIS measurements provided the best correlation to body cell mass. We suggest DXA ALM for estimation of skeletal muscle mass in patients with cirrhosis as there are established thresholds for skeletal muscle mass depletion, and an accurate assessment of bone mass and density can also be provided. The use of USMT over other bedside skeletal muscle mass estimates was not supported by our results. Further studies evaluating novel bedside skeletal muscle mass estimation techniques in cirrhosis patients are required.

Automated computed tomography (CT)-derived skeletal muscle mass determination as a significant prognostic factor in colorectal cancer patients using deep neural network model.

3534 Background: Although recent evidence suggests skeletal muscle depletion predicts the survival of patients with cancer, the retrieval and manual measurement of the computed tomography (CT) images hinder clinical application in routine clinical practice. The advent of recent deep learning applications enables highly accurate noninvasive longitudinal evaluation of skeletal muscle mass (SMM) changes. Here, we evaluated the prognostic impact of DNN-measured skeletal muscle changes in colorectal cancer (CRC) patients. Methods: A total of 6,196 newly diagnosed CRC patients were analyzed in the Yonsei Cancer Registry Database between Jan 1, 2010, and Sep 30, 2020. SMM is measured by the Skeletal muscle index (SMI). The formula used was: L3 skeletal muscle cross-sectional area (cm2)/height2 (m2). Patients’ SMI patterns were grouped by difference ratio of initial and last SMI. Patients were also classified by BMI pattern with the result of K-means clustering. Association of baseline SMI, baseline body mass index (BMI), SMI changes, BMI changes, and demographic factors with overall survival (OS) were evaluated. Univariate and multivariate analyses were conducted. Concordance (c) statistics were used to test the predictive accuracy of survival models. Results: Fully automated UNet architecture-based deep learning algorithms were applied for the third lumbar transverse CT detection, skeletal muscle segmentation, and skeletal muscle area quantification in CRC patients undergoing abdominal CT between at the time of diagnosis and one year after the diagnosis. Baseline BMI distribution was 28% obese, 26% overweight, 42% normal weight, and 4% underweight. Patients in all SMI categories varied widely in BMI. Changes in SMI were categorized into three groups: SMI increase (33%), steady (45%), and decrease (22%) group. Similarly, BMI changes were categorized into three groups: BMI increase (24%), BMI stable (57%), and BMI decrease (19%) group. Low baseline SMI, low baseline BMI, SMI decrease, and BMI decrease were independently prognostic of survival. Intriguingly, BMI and SMI changes had a different prognostic impact in men and women. For women, the SMI increase group (hazard ratio [HR], 0.4; 95% CI, 0.3-0.7; P= 0.001) was associated with longer OS, while the SMI decrease group (HR, 1.2; 95% CI, 0.6-2.2; P= 0.619) was not associated with shorter OS, both compared with SMI steady group. Conclusions: Automated CT-derived SMM depletion had a negative prognostic impact independent of BMI and age in CRC patients. A noninvasive automatic deep learning algorithm provides a unique opportunity to apply to routine clinical practice and understand how and when cachexia impacts cancer prognosis.

The Prognostic Role of Early Skeletal Muscle Mass Depletion in Multimodality Management of Patients with Advanced Gastric Cancer Treated with First Line Chemotherapy: A Pilot Experience from Modena Cancer Center.

Background: Few data about the link between nutritional status and survival are available in the metastatic gastric cancer (GC) setting. The aim of this work was to evaluate the prognostic role of tissue modifications during treatment and the benefit of a scheduled nutritional assessment in this setting. Methods: Clinical and laboratory variables of 40 metastatic GC patients treated at Modena Cancer Center were retrieved: 20 received a nutritional assessment on the oncology’s discretion, the other 20 received a scheduled nutritional assessment at baseline and every 2–4 weeks. Anthropometric parameters were calculated on Computed Tomography (CT) images at the baseline and after 3 months of chemotherapy. Results: A correlation between baseline Eastern Cooperative Oncology Group Performance Status (ECOG PS), Lymphocyte to Monocyte Ratio (LMR), C-reactive protein (PCR), Prognostic Nutritional Index (PNI) and Overall survival (OS) was highlighted. Among the anthropometric parameters, early skeletal muscle mass depletion (ESMMD) >10% in the first months of treatment significantly impacted on mOS (p = 0.0023). A link between ESMMD and baseline LDH > 460 U/L, baseline CRP > 2.2 mg/dL and weight decrease during treatment emerged. Patients evaluated with a nutritional scheduled support experienced a mean gain in subcutaneous and visceral fat of 11.4% and 10.21%, respectively. Conclusion: We confirm the prognostic impact of ESMMD > 10% during chemotherapy in metastatic GC. The prognostic role of a scheduled nutritional assessment deserves further confirmation in large prospective trials.

Impact of muscle volume loss on acute oral mucositis in patients undergoing concurrent chemoradiotherapy after oral cancer resection

This study evaluated the association between skeletal muscle mass depletion and severe oral mucositis in patients undergoing concurrent chemoradiotherapy after oral cancer resection. Skeletal muscle mass was evaluated in 60 patients using the skeletal muscle index, which was based on skeletal muscle cross-sectional area (on computed tomography) at the level of the third lumbar vertebra. In accordance with the grading criteria of the Radiation Therapy Oncology Group, patients with a grade ≥3 were defined as having severe oral mucositis. Multivariate logistic regression analysis was used to evaluate independent risk factors for severe oral mucositis. Eleven patients (18.3%) were diagnosed with low skeletal muscle mass. Severe oral mucositis occurred in 17 (28.3%) patients, and the mean skeletal muscle index was 42.8 cm2/m2. A low skeletal muscle mass (hazard ratio 18.1; P=0.001) and a chemotherapy regimen consisting of 5-fluorouracil and cisplatin (versus cisplatin only) (hazard ratio 5.5; P=0.015) were independent risk factors for severe oral mucositis. Future prospective studies are warranted to identify effective pre- and perioperative exercises and nutrition programmes to increase low skeletal muscle mass and reduce the incidence of severe oral mucositis in patients undergoing concurrent chemoradiotherapy after oral cancer resection.

Abstract IA-17: Mechanisms of pancreatic cancer-induced cachexia

Abstract Cachexia is a debilitating syndrome that results in severe, involuntary weight loss due to the depletion of skeletal muscle mass. Currently, no effective therapy exists to combat this malignant disorder. For pancreatic cancer, 85% of patients lose on average 14% of their pre-illness weight, and cachexia dramatically limits their ability to tolerate surgery, chemo- or radiotherapy. New therapies will likely evolve from an enhanced understanding of the mechanisms leading to muscle wasting and tumor development. Our laboratory has been examining the role of the NF-κB signaling pathway in tumorigenesis for several decades and that interest led us to discover the connection between NF-κB and muscle wasting in cancer cachexia and more recently in pancreatic cancer. We view the pathway as playing two separate functions in pancreatic cancer-induced cachexia. The first occurs at the level of skeletal muscle, or more preciously in skeletal muscle stem cells. We have found that during cancer progression, skeletal muscle undergoes a type of injury response leading to the activation of resident stem cells to engage in a regeneration program. NF-κB is activated in these stem cells and functions to inhibit regeneration, which contributes to the overall wasting process in cachexia. New data reveal that NF-κB activity in progenitor cells also regulates a local muscle inflammatory environment that might also contribute to skeletal muscle catabolism. The mechanism of this regulation will be discussed in more details. The second function of NF-κB signaling that we are pursuing focuses in the tumor microenvironment of pancreatic cancer. Using orthotopic mouse models of pancreatic cancer, we showed that NF-κB plays a critical role in protecting tumor cells from the surveillance property of anti-tumor macrophages. This occurs through the direct transcriptional regulation of the immunosuppressive cytokine, GDF15. Interestingly, circulating levels of GDF15 are elevated in cachectic patients and recent studies indicate that this cytokine might be an attractive therapeutic target in cancer cachexia. Together, we speculate that NF-κB functions in cancer cachexia by acting in muscle stem cells to block muscle repair, as well as promoting pancreatic cancer through the production of immunosuppressive genes such as GDF15. Citation Format: Benjamin Pryce, Nivedita Ratnam, Erin E. Talbert, Mary Dilhoff, Carl R. Schmidt, David J. Wang, Denis C. Guttridge. Mechanisms of pancreatic cancer-induced cachexia [abstract]. In: Proceedings of the AACR Virtual Special Conference on Pancreatic Cancer; 2020 Sep 29-30. Philadelphia (PA): AACR; Cancer Res 2020;80(22 Suppl):Abstract nr IA-17.

Evaluation of overall and disease-free survival in patients with free flaps for oral cancer resection.

Sarcopenia is characterized by depletion of skeletal muscle mass (SMM) and can cause increased postoperative complication in free flap procedure. One of the most important considerations while deciding the indication of the procedure is patients' survival. This study aimed to verify the relationship between low SMM and survival in patients who undergo oral cancer resection using free flap. SMM was evaluated using the skeletal muscle index (SMI cm2 /m2 ), which was defined using cross-sectional areas of skeletal muscles on computed tomography at the level of the third lumbar vertebrae normalized for height. Overall, 111 patients who underwent primary oral cancer resection and free flaps were included. Multivariate Cox regression analyses were used to evaluate the prognostic factors for survival. A total of 25 patients (22.5%) were diagnosed with low SMM. The mean SMI was 42.2 cm2 /m2 . Multivariable analyses showed that increased age (hazard ratio [HR]; 4.98, p = .004), infiltrative growth pattern INF-c (HR; 3.83, p = .037), and low SMM (HR; 2.59, p = .034) were significant negative prognostic factors for overall survival. Increased age (HR; 3.18, p = .005), extra-nodal extension (HR; 3.30, p = .001), and low SMM (HR; 2.42, p = .017) were significant negative prognostic factors for disease-free survival. Low SMM is a significant negative prognostic factor for overall and disease-free survival in oral cancer patients undergoing free flap. Future prospective studies are warranted to identify effective preoperative exercise and nutrition programs to improve low skeletal muscle and survival rate in patients undergoing free flap procedures.

Skeletal Muscle Mass Depletion After Gastrectomy Negatively Affects the Prognosis of Patients With Gastric Cancer.

Skeletal muscle mass (SMM) is often depleted in patients with gastric cancer undergoing gastrectomy. Using a novel method, we evaluated the effect of SMM depletion after gastrectomy on disease prognosis. The maximum cross-sectional area of the psoas-muscle (MCA-PM) was measured before surgery and at 1 year after in 233 patients with gastric cancer who underwent radical gastrectomy to determine the ratio (MCA-PMR) as an indicator of SMM depletion. The MCA-PMR cutoff value was set at 90%, and patients were divided into the groups with <90% and ≥90%. MCA-PMR <90% was an independent prognostic factor for all patients. In 88 patients who received adjuvant chemotherapy including S-1, the 5-year cancer-specific survival rate was significantly better for those with MCA-PMR ≥90% than for those with MCA-PMR <90% (84.1% vs. 59.1%; p=0.010; hazard ratio=2.974; 95% confidence interval=1.241-7.124). SMM depletion after gastrectomy can be measured using the MCA-PMR. This novel measurement can be easily implemented in the clinical setting.

Low skeletal muscle mass as predictor of postoperative complications and decreased overall survival in locally advanced head and neck squamous cell carcinoma: the role of ultrasound of rectus femoris muscle.

Skeletal muscle mass (SMM) depletion and sarcopenia as predictors of postoperative complications and poorer overall survival (OS) have been validated in many surgical fields through cross-sectional imaging (CT, MRI), with potential limitations. We evaluated it in a stage III-IV head and neck squamous cell carcinoma (HNSCC) surgical cohort through ultrasound (US) of rectus femoris muscle (RF), a quick, cheap, repeatable alternative. Patients submitted to surgical treatment with curative purpose were recruited and prospectively evaluated through clinical, biometric, biochemical, surgical, pathological and functional prognosticators and with preoperative US of RF with regards to 30-day complications and OS. Forty-seven patients completed the study. RF cross-sectional area (RF-CSA) was used to identify patients with low SMM (CSA ≤ 0.97cm2: 18/47, 38.3%). RF-CSA was lower in complicated cases (0.95 ± 0.48 vs 1.41 ± 0.49cm2; p = 0.003), remaining the only independent predictor of postoperative complications at multivariate analysis, with a model including ASA score and modified Frailty index (OR 9.84; p = 0.004). SMM depletion significantly impaired OS (13.6 ± 2.9 vs 26.3 ± 2.1months; p = 0.017), being its only independent prognosticator at multivariate Cox regression analysis (OR 4.42; p = 0.033). RF-CSA, evaluated with US, seems a reliable method for identification of patients with low SMM in a stage III-IV HNSCC cohort, defining a subset at high-risk of 30-day complications and poorer OS.

Impact of Sarcopenia on Early Postoperative Complications in Early-Stage Non-Small-Cell Lung Cancer.

BackgroundRisk assessment for pulmonary resection in patients with early-stage non–small-cell lung cancer (NSCLC) is important for minimizing postoperative morbidity. Depletion of skeletal muscle mass is closely associated with impaired nutritional status and limited physical ability. We evaluated the relationship between skeletal muscle depletion and early postoperative complications in patients with early-stage NSCLC.MethodsPatients who underwent curative lung resection between 2016 and 2018 and who were diagnosed with pathological stage I/II NSCLC were included, and their records were retrospectively analyzed. The psoas volume index (PVI, cm3/m3) was calculated based on computed tomography images from routine preoperative positron emission tomography-computed tomography. Early postoperative complications, defined as those occurring within 90 days of surgery, were compared between the lowest sex-specific quartile for PVI and the remaining quartiles.ResultsA strong correlation was found between the volume and the cross-sectional area of the psoas muscle (R2=0.816). The overall rate of complications was 57.6% among patients with a low PVI and 32.8% among those with a normal-to-high PVI. The most common complication was prolonged air leak (low PVI, 16.9%; normal-to-high PVI, 9.6%), followed by pneumonia (low PVI, 13.6%; normal-to-high PVI, 7.9%) and recurrent pleural effusion (low PVI, 11.9%; normal-to-high PVI, 6.8%). The predictors of overall complications were low PVI (odds ratio [OR], 2.18; 95% confidence interval [CI], 1.07–4.09; p=0.03), low hemoglobin level (OR, 0.686; 95% CI, 0.54–0.87; p=0.002), and smoking history (OR, 3.93; 95% CI, 2.03–7.58; p<0.001).ConclusionLow PVI was associated with a higher rate of early postoperative complications in patients with early-stage NSCLC.

Dietary Amino Acids and Immunonutrition Supplementation in Cancer-Induced Skeletal Muscle Mass Depletion: A Mini-Review.

Cancer patients display systemic inflammation, which leads to an increase in protein catabolism, thus promoting the release of free amino acids to further support metabolism and remodelling of muscle proteins. Inflammation associated with tumor growth leads to malnutrition, a factor that increases the risk of developing cachexia. With cancer-induced cachexia, nutritional interventions have gained traction as a preventative method to manage this condition. Currently, cancer consensus recommendations suggest a protein intake above 1.0 g/kg.day-1 up to 2.0 g/k.day-1 for cancer patients, although an ideal amount for some amino acids in isolation has yet to be determined. Due to controversy in the literature regarding the benefits of the biochemical mechanisms of various muscle mass supplements, such as L-leucine (including whey protein and BCAA), β-hydroxy-beta-methyl butyrate (HMβ), arginine, glutamine and creatine, several studies have carefully examined their effects. L-leucine and its derivatives appear to regulate protein synthesis by direct or indirect activation of the mTORC1 pool of kinases, further promoting muscle protein balance. Arginine and glutamine may act by reducing inflammation and infection progression, thus promoting improvements in food intake. Creatine exerts anabolic activity, acting as an immediate energy substrate to support muscle contraction further increasing lean mass, mainly due to greater water uptake by the muscle. In this narrative review, we highlighted the main findings regarding protein consumption and amino acids to mitigate cancer-induced skeletal muscle depletion.

Prevalence of sarcopenia and malnutrition during acute exacerbation of COPD and after 6 months recovery.

Sarcopenia defined by the association of skeletal muscle mass depletion and a decreased physical performance is underdiagnosed in chronic obstructive pulmonary disease (COPD) patients. The objective was to assess prevalence of sarcopenia and malnutrition in hospitalized COPD patients during an acute exacerbation, after 6 months follow-up and the 1-year survival. Hospitalized COPD patients were recruited for the assessment of body composition, handgrip strength, respiratory function, and maximal inspiratory and expiratory pressures (MIP and MEP), during hospitalization and 6 months later. Sarcopenia was defined according to the criteria of the European Working Group on Sarcopenia in Older Adults, malnutrition was defined according to French criteria 2007. Survival data were collected 12 months after hospitalization. We analyzed data from 54 patients, aged 68 ± 9 years and BMI 26.9 ± 7.8 kg/m2, with an average FEV1 of 1.13 ± 0.49 l (45 ± 16% predicted value). Sarcopenia and malnutrition prevalence were, respectively, 48% and 52% during hospitalization, 30% and 30% after 6 months. MIP and MEP were lower in sarcopenic patients (p = 0.01 and 0.009, respectively). In multivariate analysis, skeletal muscle mass index and MIP were positively correlated at 6 months' follow-up (r = 0.40, p = 0.04). The 1-year survival rate was lower in sarcopenic patients (65 vs 86%, p = 0.03), particularly when malnutrition was associated (p = 0.02). Sarcopenia in COPD patients is highly prevalent during and after recovery of an acute exacerbation, exposing to lower survival. A multimodal management is required to treat sarcopenia and improve prognosis.