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      The frequency of occult solid malignancy in patients with polymyalgia rheumatica-like symptoms

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          Abstract

          Aims:

          We aim to evaluate the clinical usefulness of systematic screening for occult cancer in patients with polymyalgia rheumatic (PMR)-like symptoms in real-life practice.

          Methods:

          All patients seen by rheumatologists in Burgundy, France, between March 2016 and December 2018 for new-onset PMR that met the 2012 ACR/EULAR classification criteria were prospectively included. Patients underwent systematic screening including determination of the erythrocyte sedimentation rate, serum C-reactive protein levels, thoracic, abdominal and pelvic computed tomography (CT-TAP) and, in men, serum prostate-specific antigen. The standardized incidence ratio (SIR) for cancers was calculated using 2012 national estimates of cancer incidence. Potential predictive factors for the diagnosis of cancer were then evaluated using univariate and multivariate analyses.

          Results:

          Among the 118 patients included, nine cases of cancer were confirmed and diagnosed with CT-TAP: kidney carcinoma ( n = 4), lung cancer ( n = 2), pancreatic, colon, and ampullary carcinoma ( n = 1 each). Among these cancers, five were localized (four kidney, and one ampullary carcinoma) and were treated with complete surgical resection. The expected incidence of cancer in the general population was 1.95, leading to an overall SIR of 4.6 (95% CI 2.4–8.9, p < 0.0001). An additional analysis was performed for the kidney carcinoma, and it showed a highly significant increase in SIR: 80.8 (95% CI 30.3–215.4). In 80% of patients, the PMR-like syndrome regressed during cancer treatment. No other predictive factors for cancer were found.

          Conclusion:

          Systematic screening for cancer including CT-TAP in real-life practice revealed occult solid malignancy, mostly early-stage cancer, in a relevant proportion of patients presenting PMR-like symptoms. The high proportion of kidney cancer (40%) is worth highlighting, especially considering that it is not one of the most frequent cancers after 50 years of age.

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          Most cited references27

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          Cancer of unknown primary site.

          Cancer of unknown primary site (CUP) is a well recognised clinical disorder, accounting for 3-5% of all malignant epithelial tumours. CUP is clinically characterised as an aggressive disease with early dissemination. Diagnostic approaches to identify the primary site include detailed histopathological examination with specific immunohistochemistry and radiological assessment. Gene-profiling microarray diagnosis has high sensitivity, but further prospective study is necessary to establish whether patients' outcomes are improved by its clinical use. Metastatic adenocarcinoma is the most common CUP histopathology (80%). CUP patients are divided into subsets of favourable (20%) and unfavourable (80%) prognosis. Favourable subsets are mostly given locoregional treatment or systemic platinum-based chemotherapy. Responses and survival are similar to those of patients with relevant known primary tumours. Patients in unfavourable subsets are treated with empirical chemotherapy based on combination regimens of platinum or taxane, but responses and survival are generally poor. Copyright © 2012 Elsevier Ltd. All rights reserved.
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            2012 provisional classification criteria for polymyalgia rheumatica: a European League Against Rheumatism/American College of Rheumatology collaborative initiative

            The objective of this study was to develop EULAR/ACR classification criteria for polymyalgia rheumatica (PMR). Candidate criteria were evaluated in a 6-month prospective cohort study of 125 patients with new onset PMR and 169 non-PMR comparison subjects with conditions mimicking PMR. A scoring algorithm was developed based on morning stiffness >45 minutes (2 points), hip pain/limited range of motion (1 point), absence of RF and/or ACPA (2 points), and absence of peripheral joint pain (1 point). A score ≥4 had 68% sensitivity and 78% specificity for discriminating all comparison subjects from PMR. The specificity was higher (88%) for discriminating shoulder conditions from PMR and lower (65%) for discriminating RA from PMR. Adding ultrasound, a score ≥5 had increased sensitivity to 66% and specificity to 81%. According to these provisional classification criteria, patients ≥50 years old presenting with bilateral shoulder pain, not better explained by an alternative pathology, can be classified as having PMR in the presence of morning stiffness>45 minutes, elevated CRP and/or ESR and new hip pain. These criteria are not meant for diagnostic purposes.
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              Biologic correlates of (18)fluorodeoxyglucose uptake in human breast cancer measured by positron emission tomography.

              Variable uptake of the glucose analog (18)fluorodeoxyglucose (FDG) has been noticed in positron emission tomography (PET) studies of breast cancer patients, with low uptake occurring especially in lobular cancer. At present, no satisfactory biologic explanation exists for this phenomenon. This study compared (18)FDG uptake in vivo with biomarkers expected to be involved in the underlying biologic mechanisms. Preoperative (18)FDG-PET scans were performed in 55 patients. (18)FDG activity was assessed visually by three observers using a four-point score. Tumor sections were stained by immunohistochemistry for glucose transporter-1 (Glut-1); Hexokinase (HK) I, II, and III; macrophages; hypoxia-inducible factor-1-alfa (HIF-1alpha); vascular endothelial growth factor (VEGF(165)); and microvessels. Mitotic activity index (MAI), amount of necrosis, number of lymphocytes, and tumor cells/volume were assessed. There were positive correlations between (18)FDG uptake and Glut-1 expression (P <.001), MAI (P =.001), amount of necrosis (P =.010), number of tumor cells/volume (P =.009), expression of HK I (P =.019), number of lymphocytes (P =.032), and microvessel density (r =.373; P =.005). HIF-1alpha, VEGF(165), HK II, HK III, and macrophages showed no univariate correlation with (18)FDG. In logistic regression, however, HIF-1alpha and HK II added value to MAI and Glut-1. (18)FDG uptake in breast cancer is a function of microvasculature for delivering nutrients, Glut-1 for transportation of (18)FDG into the cell, HK for entering (18)FDG into glycolysis, number of tumor cells/volume, proliferation rate (also reflected in necrosis), number of lymphocytes (not macrophages), and HIF-1alpha for upregulating Glut-1. Together, these features explain why breast cancers vary in (18)FDG uptake and elucidate the low uptake in lobular breast cancer.
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                Author and article information

                Contributors
                Journal
                Ther Adv Musculoskelet Dis
                Ther Adv Musculoskelet Dis
                TAB
                sptab
                Therapeutic Advances in Musculoskeletal Disease
                SAGE Publications (Sage UK: London, England )
                1759-720X
                1759-7218
                26 January 2021
                2021
                : 13
                : 1759720X20984275
                Affiliations
                [1-1759720X20984275]Department of Rheumatology, Dijon University Hospital, Dijon, France
                [2-1759720X20984275]INSERM UMR1098, University of Burgundy, Dijon, France
                [3-1759720X20984275]Department of Rheumatology, Saint Joseph Hospital, Marseille, France
                [4-1759720X20984275]9 Bis Rue Devosge, Dijon, Dijon, France
                [5-1759720X20984275]1 Rue G Suchon, Semur en Auxois, France
                [6-1759720X20984275]Department of Rheumatology, Dijon University Hospital, Dijon, France
                [7-1759720X20984275]INSERM UMR 1093, Cognition, Action et Plasticité sensorimotrice, University of Burgundy, Dijon, France
                [8-1759720X20984275]Department of Rheumatology, INSERM, CIC 1432, Module Plurithématique, Plateforme d’Investigation Technologique, Dijon University Hospital, Dijon, France
                [9-1759720X20984275]INSERM UMR 1093, Cognition, Action et Plasticité sensorimotrice, University of Burgundy, Dijon, France
                Author notes
                Author information
                https://orcid.org/0000-0002-4959-2348
                Article
                10.1177_1759720X20984275
                10.1177/1759720X20984275
                7844447
                33552239
                287600cf-32bc-4abe-95cd-be16cf9db6cb
                © The Author(s), 2021

                This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License ( https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access page ( https://us.sagepub.com/en-us/nam/open-access-at-sage).

                History
                : 10 September 2020
                : 4 December 2020
                Categories
                Original Research
                Custom metadata
                January-December 2021
                ts1

                cancer,ct-scan,diagnosis,polymyalgia rheumatica,screening
                cancer, ct-scan, diagnosis, polymyalgia rheumatica, screening

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