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      Chromogranin A in the Laboratory Diagnosis of Pheochromocytoma and Paraganglioma

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          Abstract

          This work discusses the clinical performance of chromogranin A (CGA), a commonly measured marker in neuroendocrine neoplasms, for the diagnosis of pheochromocytoma/paraganglioma (PPGL). Plasma CGA (cut-off value 150 µg/L) was determined by an immunoradiometric assay. Free metanephrine (cut-off value 100 ng/L) and normetanephrine (cut-off value 170 ng/L) were determined by radioimmunoassay. Blood samples were collected from PPGL patients preoperatively, one week, six months, one year and two years after adrenal gland surgery. The control patients not diagnosed with PPGL suffered from adrenal problems or from MEN2 and thyroid carcinoma. The clinical sensitivity in the PPGL group of patients (n = 71) based on CGA is 90% and is below the clinical sensitivity determined by metanephrines (97%). The clinical specificity based on all plasma CGA values after surgery (n = 98) is 99% and is the same for metanephrines assays. The clinical specificity of CGA in the control group (n = 85) was 92% or 99% using metanephrines tests. We can conclude that plasma CGA can serve as an appropriate complement to metanephrines assays in laboratory diagnosis of PPGL patients. CGA is elevated in PPGLs, as well as in other neuroendocrine or non-neuroendocrine neoplasia and under clinical conditions increasing adrenergic activity.

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          Phaeochromocytoma.

          Phaeochromocytomas are rare neuroendocrine tumours with a highly variable clinical presentation but most commonly presenting with episodes of headaches, sweating, palpitations, and hypertension. The serious and potentially lethal cardiovascular complications of these tumours are due to the potent effects of secreted catecholamines. Biochemical testing for phaeochromocytoma is indicated not only in symptomatic patients, but also in patients with adrenal incidentalomas or identified genetic predispositions (eg, multiple endocrine neoplasia type 2, von Hippel-Lindau syndrome, neurofibromatosis type 1, and mutations of the succinate dehydrogenase genes). Imaging techniques such as CT or MRI and functional ligands such as (123)I-MIBG are used to localise biochemically proven tumours. After the use of appropriate preoperative treatment to block the effects of secreted catecholamines, laparoscopic tumour removal is the preferred procedure. If removal of phaeochromocytoma is timely, prognosis is excellent. However, prognosis is poor in patients with metastases, which especially occur in patients with large, extra-adrenal tumours.
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            Nothing But NET: A Review of Neuroendocrine Tumors and Carcinomas

            This review covers the diverse topic of neuroendocrine neoplasms (NENs), a relatively rare and heterogeneous tumor type, comprising ~2% of all malignancies, with a prevalence of <200,000 in the United States, which makes it an orphan disease (Basu et al., 2010). 1 For functional purposes, NENs are divided into two groups on the basis of clinical behavior, histology, and proliferation rate: well differentiated (low grade to intermediate grade) neuroendocrine tumors and poorly differentiated (high grade) neuroendocrine carcinoma (Bosman et al., 2010) 2 ; this histological categorization/dichotomization is highly clinically relevant with respect to impact on treatment and prognosis even though it is not absolute since a subset of tumors with a low-grade appearance behaves similarly to high-grade lesions. Given the relative dearth of evidenced-based literature about this orphan disease as a whole (Modlin et al., 2008),3 since the focus of most articles is on particular anatomic subtypes of NENs (i.e., gastroenteropancreatic or pulmonary), the purpose of this review is to summarize the presentation, pathophysiology, staging, current standard of care treatments, and active areas of current research.
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              New Perspectives on Pheochromocytoma and Paraganglioma: Toward a Molecular Classification.

              A molecular biology-based taxonomy has been proposed for pheochromocytoma and paraganglioma (PPGL). Data from the Cancer Genome Atlas revealed clinically relevant prognostic and predictive biomarkers and stratified PPGLs into three main clusters. Each subgroup has a distinct molecular-biochemical-imaging signature. Concurrently, new methods for biochemical analysis, functional imaging, and medical therapies have also become available. The research community now strives to match the cluster biomarkers with the best intervention. The concept of precision medicine has been long awaited and holds great promise for improved care. Here, we review the current and future PPGL classifications, with a focus on hereditary syndromes. We discuss the current strengths and shortcomings of precision medicine and suggest a condensed manual for diagnosis and treatment of both adult and pediatric patients with PPGL. Finally, we consider the future direction of this field, with a particular focus on how advanced molecular characterization of PPGL can improve a patient's outcome, including cures and, ultimately, disease prevention.
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                Author and article information

                Journal
                Cancers (Basel)
                Cancers (Basel)
                cancers
                Cancers
                MDPI
                2072-6694
                25 April 2019
                April 2019
                : 11
                : 4
                : 586
                Affiliations
                [1 ]Institute of Endocrinology, Národní 8, 116 94 Prague, Czech Republic; evaclavikova@ 123456endo.cz
                [2 ]Department of Nuclear Medicine and Endocrinology, Motol Teaching Hospital and Second Faculty of Medicine, Charles University, V Úvalu 84, 15006 Prague 5, Czech Republic; petr.vlcek@ 123456fnmotol.cz
                [3 ]Urology Clinic, V Pražské bráně 74, 26601 Beroun, Czech Republic; lsafarik@ 123456centrum.cz
                [4 ]1st Department of Surgery-Department of Abdominal, Thoracic Surgery and Traumatology, First Faculty of Medicine, Charles University and General University Hospital, U Nemocnice 2, 12808 Prague 2, Czech Republic; david.michalsky@ 123456lf1.cuni.cz
                [5 ]Department of Urology, First Faculty of Medicine, Charles University and General University Hospital, Ke Karlovu 4, 12808 Prague 2, Czech Republic; kvetoslav.novak@ 123456vfn.cz
                [6 ]Institute of Pathology, First Faculty of Medicine, Charles University in Prague and General University Hospital, Studničkova 2, 12800 Prague 2, Czech Republic; jaroslava.duskova@ 123456lf1.cuni.cz
                [7 ]Center for Hypertension, 3rd Medical Department-Department of Endocrinology and Metabolism, First Faculty of Medicine, Charles University and General University Hospital, U Nemocnice 1, 12808 Prague 2, Czech Republic; jwidi@ 123456lf1.cuni.cz (J.W.J.); Tomas.Zelinka@ 123456lf1.cuni.cz (T.Z.)
                Author notes
                [* ]Correspondence: rbilek@ 123456endo.cz ; Tel.: +420-224-905-251
                Author information
                https://orcid.org/0000-0001-5275-9965
                https://orcid.org/0000-0001-7373-808X
                https://orcid.org/0000-0003-3395-8373
                Article
                cancers-11-00586
                10.3390/cancers11040586
                6521298
                31027285
                0486f7ed-3b0e-4732-8b02-5eac4036ee25
                © 2019 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
                : 17 March 2019
                : 17 April 2019
                Categories
                Article

                chromogranin a,metanephrines,pheochromocytoma,paraganglioma

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