Endocrine Surgery

Casola di Napoli, Italy

Endocrine Surgery

Casola di Napoli, Italy
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"These findings tell us that physicians are respecting the determination of the Afirma GEC and that, if the GEC result is benign, patients are avoiding surgery during long-term follow-up," said R. Mack Harrell, M.D., Integrative Endocrine Surgery, Memorial Health System in Boca Raton, Fla., who presented the data in a poster. "The test is helping to reduce surgeries and costs over the long-term, as it was designed to do." In another study, researchers conducted a six-year analysis of outcomes at a single clinical practice for patients whose thyroid nodules were classified as benign by the Afirma GEC. They found that approximately 30 percent of their patients who would have historically gone to surgery because of indeterminate thyroid nodule fine needle aspiration (FNA) biopsy results were able to avoid the procedure. During up to six years of follow-up, all of these patients' nodules have shown no change by serial examination or sonography. The findings were presented by Brian Michael, M.D., Wellspan Health Gettysburg Hospital and Wellspan York Hospital, during an oral session at the AACE conference. Additionally, data on the development of Veracyte's next-generation Afirma Genomic Sequencing Classifier (GSC) were presented during a poster session. The new Afirma GSC combines RNA sequencing and machine learning to leverage more enriched, previously undetectable genomic information and enhance the test's ability to distinguish benign from cancerous thyroid nodules – without unnecessary surgery. Separately, data from a pivotal clinical validation study were shared earlier during the AACE meeting. These data, conducted on a prospective, multicenter, blinded cohort, showed that the Afirma GSC maintained the current test's high sensitivity (91 percent vs. 90 percent) and significantly increased its specificity (68 percent vs. 52 percent). The Afirma GSC's negative predictive value was 96 percent, compared to 94 percent for the current test. "The long-term clinical outcome data presented at the AACE meeting reinforce that our current Afirma test has become a new standard of care in thyroid cancer diagnosis," said Bonnie Anderson, Veracyte's chief executive officer and chairman. "We believe that, by maintaining our current test's sensitivity while significantly expanding its specificity, the Afirma Genomic Sequencing Classifier will help even more patients avoid unnecessary surgery just to get a diagnosis and will further remove costs from the healthcare system." About Afirma The Afirma Genomic Sequencing Classifier is the next-generation version of the Afirma Gene Expression Classifier, and is used to identify patients with benign thyroid nodules among those with indeterminate cytopathology results in order to preserve the thyroid. Each year in the United States, more than 525,000 fine needle aspiration biopsies are performed to assess patients with potentially cancerous thyroid nodules. Up to 30 percent of the results are indeterminate (not clearly benign or malignant) and physicians have traditionally recommended thyroid surgery for a more definitive diagnosis. Following surgery, however, 70 to 80 percent of patients' nodules are diagnosed as benign, meaning the surgery was unnecessary. Such surgery is invasive, costly and often leads to the need for lifelong daily thyroid hormone replacement drugs. About Veracyte Veracyte (NASDAQ: VCYT) is a leading genomic diagnostics company that is fundamentally improving patient care by resolving diagnostic uncertainty with evidence that is trustworthy and actionable. The company's products uniquely combine genomic technology, clinical science and machine learning to provide answers that give physicians and patients a clear path forward without risky, costly surgery that is often unnecessary. Since its founding in 2008, Veracyte has commercialized three genomic tests, which are transforming the diagnosis of thyroid cancer, lung cancer and idiopathic pulmonary fibrosis and collectively target a $2 billion market opportunity. Veracyte is based in South San Francisco, California. For more information, please visit www.veracyte.com and follow the company on Twitter (@veracyte). Cautionary Note Regarding Forward-Looking Statements  This press release contains "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995. Forward-looking statements can be identified by words such as: "anticipate," "intend," "plan," "expect," "believe," "should," "may," "will" and similar references to future periods. Examples of forward-looking statements include, among others, our ability to successfully scale the company and our belief that we are well positioned for profitable growth. Forward-looking statements are neither historical facts nor assurances of future performance. Instead, they are based only on our current beliefs, expectations and assumptions regarding the future of our business, future plans and strategies, anticipated events and trends, the economy and other future conditions. Forward-looking statements involve risks and uncertainties, which could cause actual results to differ materially, and reported results should not be considered as an indication of future performance. These risks and uncertainties include, but are not limited to: the applicability of clinical results to actual outcomes; laws and regulations applicable to our business, including potential regulation by the Food and Drug Administration or other regulatory bodies; the size of the market opportunity for our products; our ability to successfully achieve adoption of and reimbursement for our products; the amount by which use of our products are able to reduce invasive procedures and misdiagnosis, and reduce healthcare costs; the occurrence and outcomes of clinical studies; the timing and publication of clinical study results; and other risks set forth in the company's filings with the Securities and Exchange Commission, including the risks set forth in the company's Quarterly Report on Form 10-Q for the quarter ended March 31, 2017. These forward-looking statements speak only as of the date hereof and Veracyte specifically disclaims any obligation to update these forward-looking statements. Veracyte, Afirma, Percepta, Envisia, the Veracyte logo, and the Afirma logo are trademarks of Veracyte, Inc. To view the original version on PR Newswire, visit:http://www.prnewswire.com/news-releases/data-presented-at-aace-2017-annual-meeting-demonstrate-long-term-clinical-utility-of-veracytes-afirma-gene-expression-classifier-in-thyroid-cancer-diagnosis-300452941.html


Mingione A.,University of Milan | Verdelli C.,IRCCS Instituto Ortopedico Galeazzi | Ferrero S.,University of Milan | Vaira V.,University of Milan | And 9 more authors.
Journal of Molecular Endocrinology | Year: 2017

Parathyroid tumors display reduced sensitivity to extracellular calcium ([Ca2+]o). [Ca2+]o activates calcium-sensing receptor (CASR), which interacts with the scaffold protein filamin A (FLNA). The study aimed to investigate: (1) the FLNA expression in human parathyroid tumors, (2) its effects on the CASR mRNA and protein expression, and (3) on ERK signaling activation, (4) the effect of the carboxy-terminal CASR variants and (5) of the treatment with the CASR agonist R568 on FLNA-mediated ERK phosphorylation in HEK293 cells. Full-length FLNA immunostaining was variably reduced in parathyroid tumors. Immunofluorescence showed that FLNA localized in membrane and cytoplasm and co-localized with CASR in parathyroid adenomas (PAds)-derived cells. Cleaved C-terminus FLNA fragment could also be detected in PAds nuclear protein fractions. In HEK293 cells transfected with 990R-CASR or 990G-CASR variants, silencing of endogenous FLNA reduced CASR mRNA levels and total and membrane-associated CASR proteins. In agreement, FLNA mRNA levels positively correlated with CASR expression in a series of 74 PAds; however, any significant correlation with primary hyperparathyroidism severity could be detected and FLNA transcript levels did not differ between PAds harboring 990R or 990G CASR variants. R568 treatment was efficient in restoring 990R-CASR and 990G-CASR sensitivity to [Ca2+]o in the absence of FLNA. In conclusion, FLNA is downregulated in parathyroid tumors and parallels the CASR expression levels. Loss of FLNA reduces CASR mRNA and protein expression levels and the CASR-induced ERK phosphorylation. FLNA is involved in receptor expression, membrane localization and ERK signaling activation of both 990R and 990G CASR variants. © 2017 Society for Endocrinology Printed in Great Britain.


Vaira V.,Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico | Elli F.,Endocrinology Unit | Elli F.,University of Milan | Forno I.,University of Milan | And 10 more authors.
Journal of Molecular Endocrinology | Year: 2012

A subset of over-expressed microRNAs (miRNAs) identified in parathyroid carcinomas (Ca) compared to normal glands belongs to C19MC, a cluster on chromosome 19q13.4 involved in stem cell biology and tumourigenesis. In this study, the expression of C19MC-MIR371-3 clusters and the molecular mechanisms presiding their modulation were investigated in a series of six normal parathyroids, 24 adenomas (Ad), 15 Ca and five matched metastases. The general expression levels of C19MC or MIR371-3 clusters in Ad lesions did not differ from normal glands, while they distinguished Ad from Ca at unsupervised hierarchical cluster analysis (P=0·0008). MIR517C showed the most significant difference in expression between Ca and Ad (P=0·0003) and it positively correlated with serum calcium, parathormone and tumour weight. In regard to the molecular mechanism determining C19MC cluster activation, we could detect C19MC copy number (CN) gain in ten Ca (67%) extending distal to the MIR371-3 cluster in almost all samples. Conversely, only four Ad (16%) showed C19MC amplification, with one case presenting distal genomic aberration to MIR371-3. Globally, CN variations of 19q13.4 loci were significantly associated with MIR517C up-regulation (P=0·006). Opposite to normal glands where C19MC promoter was methylated, hypomethylation occurred in 15 out of 30 analysed tumours. Though the epigenetic status did not correlate with C19MC miRNA expression levels, loss of C19MC promoter methylation was significantly associated with Ca and metastatic disease (P=0·01). In conclusion, C19MC cluster aberrations are a characteristic of Ca with respect to Ad. Altogether, these evidences point towards a role for 19q13.4 miRNA clusters as oncogenes in parathyroid tumourigenesis. © 2012 Society for Endocrinology.


Verdelli C.,Laboratory of Molecular Biology | Avagliano L.,University of Milan | Creo P.,Laboratory of Stem Cells for Tissue Engineering | Guarnieri V.,IRCCS Hospital Casa Sollievo Sofferenza | And 9 more authors.
Endocrine-Related Cancer | Year: 2015

Components of the tumour microenvironment initiate and promote cancer development. In this study, we investigated the stromal component of parathyroid neoplasia. Immuno-histochemistry for alpha-smooth muscle actin (α-SMA) showed an abundant periacinar distribution of α-SMA+ cells in normal parathyroid glands (nZ3). This pattern was progressively lost in parathyroid adenomas (PAds; nZ6) where α-SMA+ cells were found to surround new microvessels, as observed in foetal parathyroid glands (nZ2). Moreover, in atypical adenomas (nZ5) and carcinomas (nZ4), α-SMA+ cells disappeared from the parenchyma and accumulated in the capsula and fibrous bands. At variance with normal glands, parathyroid tumours (nZ37) expressed high levels of fibroblast-activation protein (FAP) transcripts, a marker of tumour-associated fibroblasts. We analysed the ability of PAd-derived cells to activate fibroblasts using human bone-marrow mesenchymal stem cells (hBM-MSCs). PAd-derived cells induced a significant increase in FAP and vascular endothelial growth factor A (VEGFA) mRNA levels in co-cultured hBM-MSCs. Furthermore, the role of the calcium-sensing receptor (CASR) and of the CXCL12/CXCR4 pathway in the PAd-induced activation of hBM-MSCs was investigated. Treatment of co-cultures of hBM-MSCs and PAd-derived cells with the CXCR4 inhibitor AMD3100 reduced the stimulated VEGFA levels, while CASR activation by the R568 agonist was ineffective. PAd-derived cells co-expressing parathyroid hormone (PTH)/CXCR4 and PTH/CXCL12 were identified by FACS, suggesting a paracrine/autocrine signalling. Finally, CXCR4 blockade by AMD3100 reduced PTH gene expression levels in PAd-derived cells. In conclusion, i) PAd-derived cells activated cells of mesenchymal origin; ii) PAd-associated fibroblasts were involved in tumuor neoangiogenesis and iii) CXCL12/CXCR4 pathway was expressed and active in PAd cells, likely contributing to parathyroid tumour neoangiogenesis and PTH synthesis modulation. © 2015 Society for Endocrinology.


News Article | November 30, 2016
Site: www.eurekalert.org

A team of surgeons at Mount Sinai Beth Israel (MSBI), led by William B. Inabnet III, MD, the Eugene W. Friedman, MD, Professor of Surgery and Chair for the Department of Surgery at MSBI and Chief of Endocrine Surgery Quality for the Mount Sinai Health System, have performed the first endoscopic transoral thyroidectomy in New York, and one of the first of its kind in the nation. Their initial case, which is the first published report in the United States, was recently described in the journal Surgical Endoscopy. With the assistance of Gustavo Fernandez-Ranvier, MD, and Hyunsuk Suh, MD, both Assistant Professors in the Department of Surgery at the Icahn School of Medicine at Mount Sinai, Dr. Inabnet removed the thyroid gland by making three small incisions inside the mouth underneath the lower lip. He inserted ports through the incisions, including an endoscope - a medical device with a light and camera. Once a working space within the neck area was created, Dr. Inabnet preserved the critical structures and removed the thyroid gland through the largest of the incisions. This minimally-invasive procedure leaves a hidden scar compared to the conventional transcervical approach, which leaves a visible scar on the patient's neck. "Out of all of the approaches, this is the one type of thyroid operation where there is no sign that the patient underwent surgery," said Dr. Inabnet. "This procedure is best equipped for smaller nodules and early-stage papillary thyroid cancer. I anticipate it will evolve for other applications going forward." Dr. Inabnet and his team specialize in a group of operations known as hidden-scar endoscopic thyroid surgery, which includes the transaxillary approach where incisions are made under the armpit, and the bilateral axillary breast approach, also known as BABA, where four small incisions are made in hidden locations on the chest. "The transoral route is a natural addition to our growing program of minimally invasive techniques," said Dr. Inabnet. "We now have the ability to approach the thyroid gland from below, from the side, or from above through the mouth." Dr. Inabnet has pioneered new techniques in minimally invasive endocrine neck surgery as well as adrenal and pancreatic surgery. In 1998, he helped perform the first endoscopic thyroid resection in the United States (the second in the world) and has advanced the field of video-endoscopic neck surgery. The Mount Sinai Health System is an integrated health system committed to providing distinguished care, conducting transformative research, and advancing biomedical education. Structured around seven hospital campuses and a single medical school, the Health System has an extensive ambulatory network and a range of inpatient and outpatient services--from community-based facilities to tertiary and quaternary care. The System includes approximately 7,100 primary and specialty care physicians; 12 joint-venture ambulatory surgery centers; more than 140 ambulatory practices throughout the five boroughs of New York City, Westchester, Long Island, and Florida; and 31 affiliated community health centers. Physicians are affiliated with the renowned Icahn School of Medicine at Mount Sinai, which is ranked among the highest in the nation in National Institutes of Health funding per investigator. The Mount Sinai Hospital is in the "Honor Roll" of best hospitals in America, ranked No. 15 nationally in the 2016-2017 "Best Hospitals" issue of U.S. News & World Report. The Mount Sinai Hospital is also ranked as one of the nation's top 20 hospitals in Geriatrics, Gastroenterology/GI Surgery, Cardiology/Heart Surgery, Diabetes/Endocrinology, Nephrology, Neurology/Neurosurgery, and Ear, Nose & Throat, and is in the top 50 in four other specialties. New York Eye and Ear Infirmary of Mount Sinai is ranked No. 10 nationally for Ophthalmology, while Mount Sinai Beth Israel, Mount Sinai St. Luke's, and Mount Sinai West are ranked regionally. Mount Sinai's Kravis Children's Hospital is ranked in seven out of ten pediatric specialties by U.S. News & World Report in "Best Children's Hospitals." For more information, visit http://www. , or find Mount Sinai on Facebook, Twitter and YouTube.


News Article | November 30, 2016
Site: www.prweb.com

A team of surgeons at Mount Sinai Beth Israel (MSBI), led by William B. Inabnet III, MD, the Eugene W. Friedman, MD, Professor of Surgery and Chair for the Department of Surgery at MSBI and Chief of Endocrine Surgery Quality for the Mount Sinai Health System, have performed the first endoscopic transoral thyroidectomy in New York, and one of the first of its kind in the nation. Their initial case, which is the first published report in the United States, was recently described in the journal Surgical Endoscopy. With the assistance of Gustavo Fernandez-Ranvier, MD, and Hyunsuk Suh, MD, both Assistant Professors in the Department of Surgery at the Icahn School of Medicine at Mount Sinai, Dr. Inabnet removed the thyroid gland by making three small incisions inside the mouth underneath the lower lip. He inserted ports through the incisions, including an endoscope – a medical device with a light and camera. Once a working space within the neck area was created, Dr. Inabnet preserved the critical structures and removed the thyroid gland through the largest of the incisions. This minimally-invasive procedure leaves a hidden scar compared to the conventional transcervical approach, which leaves a visible scar on the patient’s neck. “Out of all of the approaches, this is the one type of thyroid operation where there is no sign that the patient underwent surgery,” said Dr. Inabnet. “This procedure is best equipped for smaller nodules and early-stage papillary thyroid cancer. I anticipate it will evolve for other applications going forward.” Dr. Inabnet and his team specialize in a group of operations known as hidden-scar endoscopic thyroid surgery, which includes the transaxillary approach where incisions are made under the armpit, and the bilateral axillary breast approach, also known as BABA, where four small incisions are made in hidden locations on the chest. “The transoral route is a natural addition to our growing program of minimally invasive techniques,” said Dr. Inabnet. “We now have the ability to approach the thyroid gland from below, from the side, or from above through the mouth.” Dr. Inabnet has pioneered new techniques in minimally invasive endocrine neck surgery as well as adrenal and pancreatic surgery. In 1998, he helped perform the first endoscopic thyroid resection in the United States (the second in the world) and has advanced the field of video-endoscopic neck surgery. About the Mount Sinai Health System The Mount Sinai Health System is an integrated health system committed to providing distinguished care, conducting transformative research, and advancing biomedical education. Structured around seven hospital campuses and a single medical school, the Health System has an extensive ambulatory network and a range of inpatient and outpatient services—from community-based facilities to tertiary and quaternary care. The System includes approximately 7,100 primary and specialty care physicians; 12 joint-venture ambulatory surgery centers; more than 140 ambulatory practices throughout the five boroughs of New York City, Westchester, Long Island, and Florida; and 31 affiliated community health centers. Physicians are affiliated with the renowned Icahn School of Medicine at Mount Sinai, which is ranked among the highest in the nation in National Institutes of Health funding per investigator. The Mount Sinai Hospital is in the “Honor Roll” of best hospitals in America, ranked No. 15 nationally in the 2016-2017 “Best Hospitals” issue of U.S. News & World Report. The Mount Sinai Hospital is also ranked as one of the nation’s top 20 hospitals in Geriatrics, Gastroenterology/GI Surgery, Cardiology/Heart Surgery, Diabetes/Endocrinology, Nephrology, Neurology/Neurosurgery, and Ear, Nose & Throat, and is in the top 50 in four other specialties. New York Eye and Ear Infirmary of Mount Sinai is ranked No. 10 nationally for Ophthalmology, while Mount Sinai Beth Israel, Mount Sinai St. Luke's, and Mount Sinai West are ranked regionally. Mount Sinai’s Kravis Children’s Hospital is ranked in seven out of ten pediatric specialties by U.S. News & World Report in "Best Children's Hospitals." For more information, visit http://www.mountsinai.org/, or find Mount Sinai on Facebook, Twitter and YouTube.


Corbetta S.,University of Milan | Vaira V.,University of Milan | Guarnieri V.,IRCCS Hospital Casa Sollievo Della Sofferenza | Scillitani A.,IRCCS Hospital Casa Sollievo Della Sofferenza | And 8 more authors.
Endocrine-Related Cancer | Year: 2010

Parathyroid carcinoma (PaC) is a rare cause of primary hyperparathyroidism. Though the loss of the oncosuppressor CDC73/HRPT2 gene product, parafibromin, has been involved in the hyperparathyroidism-jaw tumor syndrome and in a consistent set of sporadic PaCs, parathyroid carcinogenesis remains obscure. MicroRNAs are a new class of small, non-coding RNAs implicated in development of cancer, since their deregulation can induce aberrant expression of several target genes. The aim of the present study was to identify differentially expressed microRNAs in parathyroid cancers compared with normal tissues. We performed a TaqMan low-density array profiling of four parathyroid cancers harboring CDC73 inactivating mutations and negative for parafibromin immunostaining. Their microRNA profiling was compared with that of two normal parathyroid biopsies. Out of 362 human microRNAs assayed, 279 (77%) were successfully amplified. Fourteen and three microRNAs were significantly down- and over-expressed in parathyroid cancers respectively. Of these, miR-296 and miR-139 were down-regulated, and miR-503 and miR-222 were over-expressed with a null false discovery rate. Carcinomas could be discriminated from parathyroid adenomas by a computed score based on the expression levels of miR-296, miR-222, and miR-503 as miR-139 was similarly down-regulated in both cancers and adenomas. Finally, miR-296 and miR-222 levels negatively correlated with mRNA levels of the hepatocyte growth factor receptor-regulated tyrosine kinase substrate and p27/kip1 levels respectively. These results suggest the existence of an altered microRNA expression pattern in PaCs together with a potential role of miR-296 as novel oncosuppressor gene in these neoplasia. © 2010 Society for Endocrinology Printed in Great Britain.


Kouniavsky G.,Endocrine Surgery | Kouniavsky G.,The Surgical Center | Zeiger M.A.,Endocrine Surgery | Zeiger M.A.,Johns Hopkins University
Current Opinion in Oncology | Year: 2010

Purpose of review The purpose of this review is to provide an update on recent advances in the understanding of thyroid cancer tumorigensis and implications in clinical practice. Recent findings: Recent novel and promising findings include additional abnormalities in key pathways associated with thyroid tumorigenesis (RET-Ras-BRAF-MEK; RET-β-cateinin; TRK-PI3K-AKT; and MDM-p53-PTEN), single-nucleotide polymorphisms associated with thyroid cancer susceptibility, epigenetic silencing, alternative splicing, and gene expression abnormalities. Complex regulatory mechanisms and insights into ways in which molecular aberrancies occur are becoming better understood through this research. Summary: With ongoing research, clinical problems such as the suspicious thyroid fine needle aspiration, better treatment algorithms for well differentiated thyroid cancer, and more effective treatment for anaplastic cancer will likely be found. © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins.


Gambelunghe G.,University of Perugia | Bini V.,University of Perugia | Stefanetti E.,University of Perugia | Colella R.,University of Perugia | And 3 more authors.
International Journal of Hyperthermia | Year: 2014

Purpose: The literature reports a wide range of percentages of ablation in the treatment of thyroid nodules. The aim of this nested case-control study was to evaluate whether the different morphological (well-defined vs. agglomerate) characteristics of nodules affect the success rate.Materials and methods: We selected 20 patients with a single and /or dominant well-defined nodule (group 1) and 20 with a nodular formation resulting from the fusion of multiple nodules (group 2). All the nodules were treated by the laser method receiving the same energy.Results: At 6 months, patients in group 1 showed a greater decrease in volume than those in group 2. These differences were more evident after 12 months.Conclusions: Our study demonstrates that the efficacy of laser treatment can be predicted by nodule morphology and contributes to explaining the wide differences in the percentages of ablation reported in literature. © 2014 Informa UK Ltd.

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