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      Impact of CT-Determined Sarcopenia and Body Composition on Survival Outcome in Patients with Advanced-Stage High-Grade Serous Ovarian Carcinoma

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          Abstract

          This study aimed to investigate the impact of sarcopenia and body composition on survival outcomes in Korean patients with advanced-stage high-grade serous ovarian carcinoma (HGSOC). We retrospectively identified patients diagnosed with and treated for International Federation of Gynecology and Obstetrics stage III-IV HGSOC. Skeletal muscle index (SMI) was measured using pre-treatment computed tomography scans at the third lumbar vertebra. Sarcopenia was defined as SMI <39.0 cm 2/m 2. Patients’ clinicopathologic characteristics and survival outcomes were compared according to sarcopenia presence. For subgroup analysis, we also measured the total fat area from the same image. In total, 76 and 103 patients were assigned to the sarcopenia and control groups, respectively. Comorbidities, stage, serum CA-125 levels, and size of residual tumor after surgery were similar between both groups. After a median follow up of 42.7 months, both groups showed similar progression-free survival (PFS) and overall survival (OS). In subgroup analysis confined to the sarcopenia group, patients with high fat-to-muscle ratio (FMR; ≥2.1, n = 38) showed significantly worse OS than those with low FMR (<2.1, n = 38) (5-year survival rate, 44.7% vs. 80.0%; p = 0.046), whereas PFS was not different ( p = 0.365). Multivariate analyses identified high FMR as an independent poor prognostic factor for OS in this group (adjusted hazard ratio, 3.377; 95% confidence interval, 1.170–9.752; p = 0.024). In conclusion, sarcopenia did not influence recurrence rates and survival in Korean patients with advanced-stage HGSOC. However, among the patients with sarcopenia, high FMR was associated with decreased OS.

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          The inflammatory syndrome: the role of adipose tissue cytokines in metabolic disorders linked to obesity.

          The metabolic effects of obesity have made this highly prevalent disease one of the most common risk factors for diabetes, hypertension, and atherosclerosis, the leading causes of end-stage renal failure. However, obesity per se, as defined by body mass index, is less predictive of the development of these diseases than is the presence of a constellation of obesity-related abnormalities now known as the metabolic syndrome. Recognition of this syndrome, which can readily be identified in clinical settings using defined threshold values for waist circumference, BP, fasting glucose, and dyslipidemia, allows for earlier intervention in these high-risk patients. Systemic insulin resistance has been implicated as one possible factor that links visceral obesity to adverse metabolic consequences; however, the mechanism whereby adipose tissue causes alterations in insulin sensitivity remains unclear. Infection and inflammation are commonly associated with insulin resistance, and visceral obesity is associated with a chronic, low-grade inflammatory state, suggesting that inflammation may be a potential mechanism whereby obesity leads to insulin resistance. Moreover, adipose tissue is now recognized as an immune organ that secretes numerous immunomodulatory factors and seems to be a significant source of inflammatory signals known to cause insulin resistance. Therefore, inflammation within white adipose tissue may be a crucial step contributing to the emergence of many of the pathologic features that characterize the metabolic syndrome and result in diabetes and atherosclerosis. This review describes the role of proinflammatory cytokines and hormones released by adipose tissue in generating the chronic inflammatory profile associated with visceral obesity.
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            Association of Muscle and Adiposity Measured by Computed Tomography With Survival in Patients With Nonmetastatic Breast Cancer

            Importance Sarcopenia (low muscle mass), poor muscle quality (low muscle radiodensity), and excess adiposity derived from computed tomography (CT) has been related to higher mortality in patients with metastatic breast cancer, but the association with prognosis in patients with nonmetastatic breast cancer is unknown. Objective To evaluate associations of all 3 body composition measures, derived from clinically acquired CT at diagnosis, with overall mortality in nonmetastatic breast cancer. Design, Setting, and Participants This observational study included 3241 women from Kaiser Permanente of Northern California and Dana Farber Cancer Institute diagnosed from January 2000 to December 2013 with stages II or III breast cancer. We calculated hazard ratios (HRs) to evaluate the associations of all-cause mortality with sarcopenia, low muscle radiodensity, and total adipose tissue (TAT). Models were adjusted for sociodemographics, tumor characteristics, treatment, body mass index (BMI; calculated as weight in kilograms divided by height in meters squared), and other body composition measures. We also evaluated the cross-classification of categories of sarcopenia (yes/no) and tertiles of TAT, with outcomes. Main Outcomes and Measures Overall survival time and all-cause mortality. Results Median (range) age of 3241 women included in this study was 54 (18-80) years, and median follow-up was 6.0 years; 1086 patients (34%) presented with sarcopenia, and 1199 patients (37%) had low muscle radiodensity. Among patients with nonmetastatic breast cancer, those with sarcopenia showed higher overall mortality (HR, 1.41; 95% CI, 1.18-1.69) compared with those without sarcopenia. Patients in the highest tertile of TAT also showed higher overall mortality (HR, 1.35; 95% CI, 1.08-1.69) compared with those in the lowest tertile. Low radiodensity was not associated with survival. In analyses of sarcopenia and TAT, highest mortality was seen in patients with sarcopenia and high TAT (HR, 1.89; 95% CI, 1.30-2.73); BMI alone was not significantly related to overall mortality and did not appropriately identify patients at risk of death owing to their body composition. Conclusions and Relevance Sarcopenia is underrecognized in nonmetastatic breast cancer and occurs in over one-third of newly diagnosed patients. Measures of both sarcopenia and adiposity from clinically acquired CT scans in nonmetastatic patients provide significant prognostic information that outperform BMI and will help to guide interventions to optimize survival outcomes. This observational study examines associations of sarcopenia, muscle radiodensity, and adiposity with overall mortality in nonmetastatic breast cancer. Question Are sarcopenia, poor muscle quality, and excess adiposity at diagnosis associated with overall mortality in patients with nonmetastatic breast cancer? Findings In this observational study of 3241 patients with breast cancer, more than one-third presented with sarcopenia at diagnosis, and those women had a significantly increased risk of death compared with patients without sarcopenia. Poor muscle quality was not associated with survival, and highest mortality was in patients with sarcopenia and high total adipose tissue. Meaning Measures of sarcopenia provide significant prognostic information in nonmetastatic breast cancer and will help to identify high-risk groups and guide interventions to optimize survival outcomes.
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              Sarcopenic obesity: hidden muscle wasting and its impact for survival and complications of cancer therapy

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                Author and article information

                Journal
                Cancers (Basel)
                Cancers (Basel)
                cancers
                Cancers
                MDPI
                2072-6694
                28 February 2020
                March 2020
                : 12
                : 3
                : 559
                Affiliations
                [1 ]Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul 03080, Korea; seikky@ 123456naver.com (S.I.K.); marialeemd@ 123456gmail.com (M.L.); bboddi0311@ 123456gmail.com (H.S.K.); chhkmj1@ 123456snu.ac.kr (H.H.C.)
                [2 ]Department of Radiology, Seoul National University College of Medicine, Seoul 03080, Korea; kjambong@ 123456gmail.com (T.M.K.); radjycho@ 123456snu.ac.kr (J.Y.C.)
                [3 ]Cancer Research Institute, Seoul National University College of Medicine, Seoul 03080, Korea
                Author notes
                [* ]Correspondence: yssong@ 123456snu.ac.kr ; Tel.: +82-2-2072-2822
                [†]

                These two authors contributed equally as first authors.

                Author information
                https://orcid.org/0000-0002-9790-6735
                https://orcid.org/0000-0002-8017-3176
                https://orcid.org/0000-0001-6876-8671
                https://orcid.org/0000-0001-7115-4021
                Article
                cancers-12-00559
                10.3390/cancers12030559
                7139516
                32121099
                da52e46f-8e2e-4ebb-bdfe-7d0e33505043
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 04 February 2020
                : 26 February 2020
                Categories
                Article

                ovarian neoplasms,high-grade serous carcinoma,sarcopenia,body composition,prognosis,survival

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