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      Osteopenia is associated with wasting in pancreatic adenocarcinoma and predicts survival after surgery

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          Abstract

          Pancreatic ductal adenocarcinoma (PDAC) is among the deadliest of all common malignancies. Treatment is difficult and often complicated by the presence of cachexia. The clinical portrait of cachexia contributes to the poor prognosis experienced by PDAC patients and worsens therapeutic outcomes. We propose that low bone mineral density is a component of cachexia, which we explore herein through a retrospective review of all patients at our facility that underwent surgery for PDAC between 2011 and 2018 and compared to sex‐, age‐ and comorbidity‐matched control individuals. Data were abstracted from the medical record and pre‐operative computed tomography scans. Muscle mass and quality were measured at the L3 level and bone mineral density was measured as the radiation attenuation of the lumbar vertebral bodies. Patients with PDAC displayed typical signs of cachexia such as weight loss and radiologically appreciable deterioration of skeletal muscle. Critically, PDAC patients had significantly lower bone mineral density than controls, with 61.2% of PDAC patients categorized as osteopenic compared to 36.8% of controls. PDAC patients classified as osteopenic had significantly reduced survival (1.01 years) compared to patients without osteopenia (2.77 years). The presence of osteopenia was the strongest clinical predictor of 1‐ and 2‐year disease‐specific mortality, increasing the risk of death by 107% and 80%, respectively. Osteopenia serves as a test of 2‐year mortality with sensitivity of 76% and specificity of 58%. These data therefore identify impaired bone mineral density as a key component of cachexia and predictor of postoperative survival in patients with PDAC. The mechanisms that lead to bone wasting in tumor‐bearing hosts deserve further study.

          Abstract

          Bone density loss accompanies skeletal muscle atrophy in pancreatic cancer. Osteopenia is the single strongest predictor of 2‐year survival following curative surgery.

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          Most cited references40

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          Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey.

          Although quality assessment is gaining increasing attention, there is still no consensus on how to define and grade postoperative complications. This shortcoming hampers comparison of outcome data among different centers and therapies and over time. A classification of complications published by one of the authors in 1992 was critically re-evaluated and modified to increase its accuracy and its acceptability in the surgical community. Modifications mainly focused on the manner of reporting life-threatening and permanently disabling complications. The new grading system still mostly relies on the therapy used to treat the complication. The classification was tested in a cohort of 6336 patients who underwent elective general surgery at our institution. The reproducibility and personal judgment of the classification were evaluated through an international survey with 2 questionnaires sent to 10 surgical centers worldwide. The new ranking system significantly correlated with complexity of surgery (P < 0.0001) as well as with the length of the hospital stay (P < 0.0001). A total of 144 surgeons from 10 different centers around the world and at different levels of training returned the survey. Ninety percent of the case presentations were correctly graded. The classification was considered to be simple (92% of the respondents), reproducible (91%), logical (92%), useful (90%), and comprehensive (89%). The answers of both questionnaires were not dependent on the origin of the reply and the level of training of the surgeons. The new complication classification appears reliable and may represent a compelling tool for quality assessment in surgery in all parts of the world.
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            Projecting cancer incidence and deaths to 2030: the unexpected burden of thyroid, liver, and pancreas cancers in the United States.

            Cancer incidence and deaths in the United States were projected for the most common cancer types for the years 2020 and 2030 based on changing demographics and the average annual percentage changes in incidence and death rates. Breast, prostate, and lung cancers will remain the top cancer diagnoses throughout this time, but thyroid cancer will replace colorectal cancer as the fourth leading cancer diagnosis by 2030, and melanoma and uterine cancer will become the fifth and sixth most common cancers, respectively. Lung cancer is projected to remain the top cancer killer throughout this time period. However, pancreas and liver cancers are projected to surpass breast, prostate, and colorectal cancers to become the second and third leading causes of cancer-related death by 2030, respectively. Advances in screening, prevention, and treatment can change cancer incidence and/or death rates, but it will require a concerted effort by the research and healthcare communities now to effect a substantial change for the future. ©2014 American Association for Cancer Research.
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              Definition and classification of cancer cachexia: an international consensus.

              To develop a framework for the definition and classification of cancer cachexia a panel of experts participated in a formal consensus process, including focus groups and two Delphi rounds. Cancer cachexia was defined as a multifactorial syndrome defined by an ongoing loss of skeletal muscle mass (with or without loss of fat mass) that cannot be fully reversed by conventional nutritional support and leads to progressive functional impairment. Its pathophysiology is characterised by a negative protein and energy balance driven by a variable combination of reduced food intake and abnormal metabolism. The agreed diagnostic criterion for cachexia was weight loss greater than 5%, or weight loss greater than 2% in individuals already showing depletion according to current bodyweight and height (body-mass index [BMI] <20 kg/m(2)) or skeletal muscle mass (sarcopenia). An agreement was made that the cachexia syndrome can develop progressively through various stages--precachexia to cachexia to refractory cachexia. Severity can be classified according to degree of depletion of energy stores and body protein (BMI) in combination with degree of ongoing weight loss. Assessment for classification and clinical management should include the following domains: anorexia or reduced food intake, catabolic drive, muscle mass and strength, functional and psychosocial impairment. Consensus exists on a framework for the definition and classification of cancer cachexia. After validation, this should aid clinical trial design, development of practice guidelines, and, eventually, routine clinical management. Copyright © 2011 Elsevier Ltd. All rights reserved.
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                Author and article information

                Contributors
                arjudge@phhp.ufl.edu
                Journal
                Cancer Med
                Cancer Med
                10.1002/(ISSN)2045-7634
                CAM4
                Cancer Medicine
                John Wiley and Sons Inc. (Hoboken )
                2045-7634
                17 November 2021
                January 2022
                : 11
                : 1 ( doiID: 10.1002/cam4.v11.1 )
                : 50-60
                Affiliations
                [ 1 ] Department of Physical Therapy University of Florida Gainesville Florida USA
                [ 2 ] Department of Surgery University of Florida Gainesville Florida USA
                [ 3 ] MD‐PhD Training Program University of Florida Gainesville Florida USA
                [ 4 ] Department of Medicine University of Florida Gainesville Florida USA
                [ 5 ] Malcolm Randall VA Medical Center Gainesville Florida USA
                [ 6 ] Department of Surgery Virginia Commonwealth University Richmond Virginia USA
                Author notes
                [*] [* ] Correspondence

                Andrew R. Judge, University of Florida, Box 100154, UFHSC, Gainesville, FL 32610‐0154, USA.

                Email: arjudge@ 123456phhp.ufl.edu

                Author information
                https://orcid.org/0000-0002-6249-9180
                https://orcid.org/0000-0002-4488-291X
                Article
                CAM44416
                10.1002/cam4.4416
                8704155
                34791809
                d6f3b165-bbd1-4717-a24e-2f39ee5f7dea
                © 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 14 October 2021
                : 10 February 2021
                : 28 October 2021
                Page count
                Figures: 5, Tables: 3, Pages: 11, Words: 7486
                Funding
                Funded by: National Institute of Arthritis and Musculoskeletal and Skin Diseases , doi 10.13039/100000069;
                Award ID: R01AR060209
                Categories
                Research Article
                Clinical Cancer Research
                Research Articles
                Custom metadata
                2.0
                January 2022
                Converter:WILEY_ML3GV2_TO_JATSPMC version:6.7.0 mode:remove_FC converted:24.12.2021

                Oncology & Radiotherapy
                bone‐muscle interactions,cytokines,human association studies,prognostic markers,sarcopenia,tumor‐induced bone disease

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