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https://www.readbyqxmd.com/read/29663329/prophylactic-thyroidectomy-in-children-with-multiple-endocrine-neoplasia-type-2
#1
F P Prete, T Abdel-Aziz, C Morkane, C Brain, T R Kurzawinski
BACKGROUND: In patients with multiple endocrine neoplasia type 2 (MEN2) syndrome, genetic testing offers early diagnosis, stratifies the risk of developing medullary thyroid cancer (MTC) and informs the timing of thyroidectomy. The efficacy of treatment, which depends on timely and safe surgery, is not well established. METHODS: This was a retrospective review of diagnostic and clinicopathological outcomes of prophylactic thyroidectomy in children with MEN2 between 1995 and 2013 in the UK...
April 17, 2018: British Journal of Surgery
https://www.readbyqxmd.com/read/29663167/structural-studies-on-radiopharmaceutical-dota-minigastrin-analogue-cp04-complexes-and-their-interaction-with-cck2-receptor
#2
Piotr F J Lipiński, Piotr Garnuszek, Michał Maurin, Raphael Stoll, Nils Metzler-Nolte, Artur Wodyński, Jan Cz Dobrowolski, Marta K Dudek, Monika Orzełowska, Renata Mikołajczak
BACKGROUND: The cholecystokinin receptor subtype 2 (CCK-2R) is an important target for diagnostic imaging and targeted radionuclide therapy (TRNT) due to its overexpression in certain cancers (e.g., medullary thyroid carcinoma (MTC)), thus matching with a theranostic principle. Several peptide conjugates suitable for the TRNT of MTC have been synthesized, including a very promising minigastrin analogue DOTA-(DGlu)6 -Ala-Tyr-Gly-Trp-Met-Asp-Phe-NH2 (CP04). In this contribution, we wanted to see whether CP04 binding affinity for CCK-2R is sensitive to the type of the complexed radiometal, as well as to get insights into the structure of CP04-CCK2R complex by molecular modeling...
April 16, 2018: EJNMMI Research
https://www.readbyqxmd.com/read/29657135/precision-targeted-therapy-with-blu-667-for-ret-driven-cancers
#3
Vivek Subbiah, Justin F Gainor, Rami Rahal, Jason D Brubaker, Joseph L Kim, Michelle Maynard, Wei Hu, Qiongfang Cao, Michael P Sheets, Douglas Wilson, Kevin J Wilson, Lucian DiPietro, Paul Fleming, Michael Palmer, Mimi I Hu, Lori Wirth, Marcia S Brose, Sai-Hong Ignatius Ou, Matthew Taylor, Elena Garralda, Stephen Miller, Beni Wolf, Christoph Lengauer, Timothy Guzi, Erica K Evans
The receptor tyrosine kinase, rearranged during transfection (RET), is an oncogenic driver activated in multiple cancers including non-small cell lung cancer (NSCLC), medullary thyroid cancer (MTC) and papillary thyroid cancer (PTC). No approved therapies have been designed to target RET; treatment has been limited to multi-kinase inhibitors (MKIs) which can have significant off-target toxicities and limited efficacy. BLU-667 is a highly potent and selective RET inhibitor designed to overcome these limitations...
April 15, 2018: Cancer Discovery
https://www.readbyqxmd.com/read/29656518/genotype-specific-progression-of-hereditary-medullary-thyroid-cancer
#4
Andreas Machens, Kerstin Lorenz, Frank Weber, Henning Dralle
Although already 25 years into the genomic era, age-related progression of hereditary medullary thyroid cancer (MTC), the prevalence of which is estimated at 1 in 80,000 inhabitants, remains to be delineated for most unique RET (REarranged during Transfection) mutations. Included in this study were 567 RET carriers. The age-related progression of MTC across histopathological groups (normal thyroid/C-cell hyperplasia; node-negative MTC; node-positive MTC) was statistically significant for 13 unique RET mutations (p...
April 14, 2018: Human Mutation
https://www.readbyqxmd.com/read/29644341/uptake-of-99m-tc-mibi-by-sclerosing-pneumocytoma-raising-a-false-suspicion-of-metastasis-from-medullary-thyroid-carcinoma
#5
Georgios E Papadakis, Flavian Tabotta, Igor Levotanec, Michel Gonzalez, John O Prior, Stefano La Rosa, Gerasimos P Sykiotis
Technetium-99m methoxy isobutyl isonitrile (99m Tc-MIBI; sestamibi) single-photon emission computed tomography (SPECT)/computed tomography (CT) performed for preoperative localization of parathyroid adenomas or for other indications can reveal incidentalomas. Interpretation of such findings can be challenging, particularly when thyroid or other endocrine tumors are also present. Preoperative staging of a 59-year-old female patient with medullary thyroid carcinoma (MTC) showing moderate hypermetabolism on 18 F-fluorodeoxyglucose positron emission tomography/CT also detected a slightly hypermetabolic pulmonary nodule (standardized uptake value normalized by body weight max = 2...
April 1, 2018: Journal of the Endocrine Society
https://www.readbyqxmd.com/read/29643661/unusual-metastasis-of-medullary-thyroid-carcinoma-to-the-breast-a-cytological-and-histopathological-correlation
#6
Parul Tanwar, Jatin S Gandhi, Anila Sharma, Manoj Gupta, Partha S Choudhary
Breast metastases are a relatively rare condition and account for approximately 0.5-2% of all breast tumors. Recognition of metastatic tumors in the breast is important because it would prevent unnecessary mutilating surgery and would lead to appropriate treatment of the primary tumor. Breast metastases from medullary thyroid cancer (MTC) are very rare with only 21 reported cases in the literature. Some MTCs mimic primary invasive lobular carcinoma of the breast histopathologically and radiologically, making the distinction between the two diagnostically challenging...
April 2018: Journal of Cytology
https://www.readbyqxmd.com/read/29642647/erbb1-and-erbb2-positive-medullary-thyroid-carcinoma-a-case-report
#7
Michele Minuto, Emanuela Varaldo, Gianluca Marcocci, Amleto de Santanna, Ermanno Ciccone, Katia Cortese
Medullary thyroid carcinomas (MTCs) are rare thyroid tumors occurring in both sporadic and hereditary forms, whose pathogenesis is related to RET proto-oncogene alterations. MTCs originate from parafollicular cells, which produce calcitonin that represents the biochemical activity of MTC. Total thyroidectomy is the main treatment for MTC and often cures patients with confined diseases. In the presence of metastasis, the therapeutic approach depends on the rate of disease progression. We report a case of a 54-year-old female with a single, incidentally discovered, thyroid nodule of 1 cm, classified as suspicious MTC after a stimulation test with intravenous (iv) calcium...
April 10, 2018: Diseases (Basel)
https://www.readbyqxmd.com/read/29615431/clinical-significance-of-ret-and-ras-mutations-in-sporadic-medullary-thyroid-cancer-a-meta-analysis
#8
Huy Gia Vuong, Toru Odate, Hanh T T Ngo, Thong Quang Pham, Thao T K Tran, Kunio Mochizuki, Tadao Nakazawa, Ryohei Katoh, Tetsuo Kondo
There are ongoing debates with respect to the prognostic roles of molecular biomarkers in sporadic medullary thyroid carcinoma (MTC). In this study, we aimed at investigating the prognostic value of RET and RAS mutations - the two most common mutations in sporadic MTCs. A search was conducted in four electronic databases. Relevant data were extracted and pooled into odds ratios (OR), mean differences (MD) and corresponding 95% confidence intervals (CI) using the random-effect model. We used Egger's regression test and visual of funnel plots to assess the publication bias...
April 3, 2018: Endocrine-related Cancer
https://www.readbyqxmd.com/read/29599750/postoperative-neck-ultrasonography-surveillance-after-thyroidectomy-in-patients-with-medullary-thyroid-carcinoma-a-multicenter-study
#9
Hye Shin Ahn, Dong Wook Kim, Yoo Jin Lee, Chang Yoon Lee, Ji-Hoon Kim, Yoon Jung Choi, Song Lee, Inseon Ryoo, Jung Yin Huh, Jin Yong Sung, Jin Young Kwak, Hye Jin Baek
Background: For detecting tumor recurrence of medullary thyroid carcinoma (MTC) in the neck, an appropriate frequency and interval of postoperative ultrasonography (US) surveillance remains unclear. This study aimed to assess an appropriate interval and frequency of postoperative neck US surveillance for detecting tumor recurrence in patients who had undergone thyroid surgery due to MTC. Methods: A total of 86 patients who had undergone thyroid surgery for the treatment of MTC and had at least one postoperative US follow-up examination at any of nine affiliated hospitals were included...
2018: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/29590403/p-val804met-the-most-frequent-pathogenic-mutation-in-ret-confers-a-very-low-lifetime-risk-of-medullary-thyroid-cancer
#10
Chey Loveday, Katherine Josephs, Daniel Chubb, Adam Gunning, Louise Izatt, Marc Tischkovitz, Sian Ellard, Clare Turnbull
Context: To date, penetrance figures for medullary thyroid cancer (MTC) for variants in RET have been estimated from families ascertained on account of presence of MTC. Objective: To gain estimates of penetrance unbiased by ascertainment, we analyzed 61 RET mutations assigned as disease-causing by the ATA in population whole exome sequencing data. Design: For the 61 RET mutations, we used analyses of the observed allele frequencies in ∼51,000 individuals from non-TCGA ExAC, assuming lifetime penetrance for MTC of 90%, 50% and unbounded...
March 23, 2018: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/29581064/molecular-signatures-of-medullary-thyroid-carcinoma-by-matrix-assisted-laser-desorption-ionisation-mass-spectrometry-imaging
#11
Andrew Smith, Manuel Galli, Isabella Piga, Vanna Denti, Martina Stella, Clizia Chinello, Nicola Fusco, Davide Leni, Marco Manzoni, Gaia Roversi, Mattia Garancini, Angela Ida Pincelli, Vincenzo Cimino, Giulia Capitoli, Fulvio Magni, Fabio Pagni
The main aim of the study was to assess the feasibility of matrix-assisted laser desorption/ionisation mass spectrometry imaging (MALDI-MSI) in the pathological investigation of Medullary Thyroid Carcinoma (MTC). Formalin-fixed paraffin-embedded (FFPE) samples from seven MTC patients were analysed by MALDI-MSI in order to detect proteomic alterations within tumour lesions and to define the molecular profiles of specific findings, such as amyloid deposition and C cell hyperplasia (CCH). nLC-ESI MS/MS was employed for the identification of amyloid components and to select alternative proteomic markers of MTC pathogenesis...
March 24, 2018: Journal of Proteomics
https://www.readbyqxmd.com/read/29579362/barriers-to-the-recognition-of-medullary-thyroid-carcinoma-on-fna-implications-relevant-to-the-new-american-thyroid-association-guidelines
#12
Kathryn S Dyhdalo, Deborah J Chute
BACKGROUND: The 2016 American Thyroid Association guidelines recommend multiple endocrine neoplasia testing and evaluation for pheochromocytoma before thyroidectomy after a thyroid fine-needle aspiration biopsy (FNA) is positive for medullary thyroid carcinoma (MTC). In the current study, the authors examined the reasons why FNA was unable to definitively diagnose MTC preoperatively, with attention to morphologic patterns that can be misleading. METHODS: Cases of MTC diagnosed on thyroid surgical resection for which there was a prior FNA and slides available for review were included (28 cases)...
March 26, 2018: Cancer Cytopathology
https://www.readbyqxmd.com/read/29572709/the-antiproliferative-effect-of-pasireotide-lar-alone-and-in-combination-with-everolimus-in-patients-with-medullary-thyroid-cancer-a-single-center-open-label-phase-ii-proof-of-concept-study
#13
Antongiulio Faggiano, Roberta Modica, Rosa Severino, Luigi Camera, Rosa Fonti, Michela Del Prete, Maria Grazia Chiofalo, Massimo Aria, Piero Ferolla, Giovanni Vitale, Luciano Pezzullo, Annamaria Colao
PURPOSE: Medullary thyroid cancer (MTC) is a neuroendocrine tumour of the thyroid C cells. Pasireotide, a multi-receptor targeted somatostatin analogue, and everolimus, an inhibitor of mTOR, showed antitumour properties in neuroendocrine tumours. Aim of this study was to evaluate pasireotide alone and in combination with everolimus in patients with MTC. METHODS: Patients with progressive metastatic or persistent postoperative MTC received pasireotide LAR 60 mg/m for at least 6 months...
March 23, 2018: Endocrine
https://www.readbyqxmd.com/read/29571788/network-wise-cerebral-blood-flow-redistribution-after-20-hz-rtms-on-left-dorso-lateral-prefrontal-cortex
#14
Yuan-Qi Shang, Jun Xie, Wei Peng, Jian Zhang, Da Chang, Ze Wang
The repetitive application of transcranial magnetic stimulation (rTMS) on left dorsolateral prefrontal cortex (DLPFC) has been consistently shown to be beneficial for treating various neuropsychiatric or neuropsychological disorders, but its neural mechanisms still remain unclear. The purpose of this study was to measure the effects of high-frequency left DLPFC rTMS using cerebral blood flow (CBF) collected from 40 young healthy subjects before and after applying 20 Hz left DLPFC rTMS or SHAM stimulations...
April 2018: European Journal of Radiology
https://www.readbyqxmd.com/read/29569965/analysis-of-risk-factors-for-cervical-lymph-node-metastases-in-patients-with-sporadic-medullary-thyroid-carcinoma
#15
Weina Fan, Cheng Xiao, Fusheng Wu
Objective Medullary thyroid carcinoma (MTC) is classified as either sporadic or inherited. This study was performed to analyze the risk factors for cervical lymph node metastases and predict the indication for prophylactic lateral neck dissection in patients with sporadic MTC. Methods Sixty-five patients with sporadic MTC were retrospectively reviewed. Univariate analysis with the chi-square test and multiple logistic regression analysis were applied to identify the clinicopathological features (sex, age, tumor size, number of tumor foci, capsule or vascular invasion, and others) associated with cervical lymph node metastases...
January 1, 2018: Journal of International Medical Research
https://www.readbyqxmd.com/read/29563735/outcome-of-treatment-for-medullary-thyroid-carcinoma-a-single-centre-experience
#16
Anish Jacob Cherian, Pooja Ramakant, Rekha Pai, Marie Therese Manipadam, S Elanthenral, Anuradha Chandramohan, Julie Hephzibah, David Mathew, Dhukabandhu Naik, Thomas V Paul, Simon Rajaratnam, Nihal Thomas, M J Paul, Deepak Thomas Abraham
We conducted this study to evaluate the demography, clinical presentation, management and outcomes of medullary thyroid carcinoma (MTC) from the Indian context. This was a retrospective study of patients with MTC managed between January 2008 and December 2016. All pertinent data was collected and the results were analysed using STATA (v.13.1). MTC accounted for 90/2022 (4.45%) patients managed with thyroid cancer during the study period. The mean age of presentation was 40 years (range 14-70 years) with 47 males and 43 females...
March 2018: Indian Journal of Surgical Oncology
https://www.readbyqxmd.com/read/29549836/challenging-clinically-unresponsive-medullary-thyroid-cancer-discovery-and-pharmacological-activity-of-novel-ret-inhibitors
#17
Valeria La Pietra, Stefania Sartini, Lorenzo Botta, Alessandro Antonelli, Silvia Martina Ferrari, Poupak Fallahi, Alessio Moriconi, Vito Coviello, Luca Quattrini, Yi-Yu Ke, Hsieh Hsing-Pang, Federico Da Settimo, Ettore Novellino, Concettina La Motta, Luciana Marinelli
It is now known that "gain of function" mutations of RET (REarranged during Transfection) kinase are specific and key oncogenic events in the onset of thyroid gland cancers such as the Medullary Thyroid Carcinoma (MTC). Although a number of RET inhibitors exist and are capable of inhibiting RET variants, in which mutations are outside the enzyme active site, the majority becomes dramatically ineffective when mutations are within the protein active site (V804L and V804M). Pursuing a receptor-based virtual screening against the kinase domain of RET, we found that compound 5 is able to inhibit efficiently both wild type and V804L mutant RET...
March 2, 2018: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29547606/medullary-thyroid-cancer-overview-and-case-study-of-a-rare-cancer
#18
Lynn Jakobs
BACKGROUND: Medullary thyroid cancer (MTC) is a rare cancer that has historically been managed by endocrinologists. In 2011, the first of several multi- targeted tyrosine kinase inhibitors was approved as treatment for MTC. These drugs have changed the management of MTC to teams that include oncologists and oncology nurses. OBJECTIVES: This article illustrates MTC diagnostics, surveillance, management of adverse drug reactions, and disease progression through a case study...
April 1, 2018: Clinical Journal of Oncology Nursing
https://www.readbyqxmd.com/read/29544469/thyroid-cancer-trends-in-incidence-mortality-and-clinical-pathological-patterns-in-zhejiang-province-southeast-china
#19
Lingbin Du, Youqing Wang, Xiaohui Sun, Huizhang Li, Xinwei Geng, Minghua Ge, Yimin Zhu
BACKGROUND: Thyroid cancer is the most common malignant disease of the endocrine system. Previous studies indicate a rapid increase in the incidence of thyroid cancer in recent decades, and this increase has aroused the great public concern. The aim of this study was to analyze the trends in incidence, mortality and clinical-pathological patterns of thyroid cancer in Zhejiang province. METHODS: Population-based incidence and mortality rates of thyroid cancer were collected from eight cancer registries in Zhejiang from 2000 to 2012...
March 15, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29540936/bayesian-mixed-treatment-comparisons-meta-analysis-for-correlated-outcomes-subject-to-reporting-bias
#20
Yulun Liu, Stacia M DeSantis, Yong Chen
Many randomized controlled trials (RCTs) report more than one primary outcome. As a result, multivariate meta-analytic methods for the assimilation of treatment effects in systematic reviews of RCTs have received increasing attention in the literature. These methods show promise with respect to bias reduction and efficiency gain compared to univariate meta-analysis. However, most methods for multivariate meta-analysis have focused on pairwise treatment comparisons (i.e., when the number of treatments is two)...
January 2018: Journal of the Royal Statistical Society. Series C, Applied Statistics
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