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1.
Endocr Relat Cancer ; 27(6): R145-R161, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32229700

RESUMO

Metastatic duodenopancreatic neuro-endocrine tumors (dpNETs) are the most important disease-related cause of death in patients with multiple endocrine neoplasia type 1 (MEN1). Nonfunctioning pNETs (NF-pNETs) are highly prevalent in MEN1 and clinically heterogeneous. Therefore, management is controversial. Data on prognostic factors for risk stratification are limited. This systematic review aims to establish the current state of evidence regarding prognostic factors in MEN1-related NF-pNETs. We systematically searched four databases for studies assessing prognostic value of any factor on NF-pNET progression, development of distant metastases, and/or overall survival. In- and exclusion, critical appraisal and data-extraction were performed independently by two authors according to pre-defined criteria. Thirteen studies (370 unique patients) were included. Prognostic factors investigated were tumor size, timing of surgical resection, WHO grade, methylation, p27/p18 expression by immunohistochemistry (IHC), ARX/PDX1 IHC and alternative lengthening of telomeres. Results were complemented with evidence from studies in MEN1-related pNET for which data could not be separately extracted for NF-pNET and data from sporadic NF-pNET. We found that the most important prognostic factors used in clinical decision making in MEN1-related NF-pNETs are tumor size and grade. NF-pNETs <2 cm may be managed with watchful waiting, while surgical resection is advised for NF-pNETs ≥2 cm. Grade 2 NF-pNETs should be considered high risk. The most promising and MEN1-relevant avenues of prognostic research are multi-analyte circulating biomarkers, tissue-based molecular factors and imaging-based prognostication. Multi-institutional collaboration between clinical, translation and basic scientists with uniform data and biospecimen collection in prospective cohorts should advance the field.


Assuntos
Neoplasia Endócrina Múltipla Tipo 1/genética , Feminino , Humanos , Masculino , Prognóstico , Resultado do Tratamento
2.
Clin Radiol ; 75(6): 479.e17-479.e22, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32089260

RESUMO

AIM: To determine the value of contrast-enhanced computed tomography (CT)-derived radiomic features in the preoperative prediction of Ki-67 expression in adrenocortical carcinoma (ACC) and to detect significant associations between radiomic features and Ki-67 expression in ACC. MATERIALS AND METHODS: For this retrospective analysis, patients with histopathologically proven ACC were reviewed. Radiomic features were extracted for all patients from the preoperative contrast-enhanced abdominal CT images. Statistical analysis identified the radiomic features predicting the Ki-67 index in ACC and analysed the correlation with the Ki-67 index. RESULTS: Fifty-three cases of ACC that met eligibility criteria were identified and analysed. Of the radiomic features analysed, 10 showed statistically significant differences between the high and low Ki-67 expression subgroups. Multivariate linear regression analysis yielded a predictive model showing a significant association between radiomic signature and Ki-67 expression status in ACC (R2=0.67, adjusted R2=0.462, p=0.002). Further analysis of the independent predictors showed statistically significant correlation between Ki-67 expression and shape flatness, elongation, and grey-level long run emphasis (p=0.002, 0.01, and 0.04, respectively). The area under the curve for identification of high Ki-67 expression status was 0.78 for shape flatness and 0.7 for shape elongation. CONCLUSION: Radiomic features derived from preoperative contrast-enhanced CT images show encouraging results in the prediction of the Ki-67 index in patients with ACC. Morphological features, such as shape flatness and elongation, were superior to other radiomic features in the detection of high Ki-67 expression.


Assuntos
Neoplasias do Córtex Suprarrenal/diagnóstico por imagem , Neoplasias do Córtex Suprarrenal/metabolismo , Carcinoma Adrenocortical/diagnóstico por imagem , Carcinoma Adrenocortical/metabolismo , Antígeno Ki-67/metabolismo , Tomografia Computadorizada por Raios X/métodos , Neoplasias do Córtex Suprarrenal/cirurgia , Carcinoma Adrenocortical/cirurgia , Biomarcadores Tumorais/metabolismo , Meios de Contraste , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Período Pré-Operatório , Estudos Retrospectivos
3.
Endocr Relat Cancer ; 27(8): T9-T25, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32069215

RESUMO

The PanNET Working Group of the 16th International Multiple Endocrine Neoplasia Workshop (MEN2019) convened in Houston, TX, USA, 27-29 March 2019 to discuss key unmet clinical needs related to PanNET in the context of MEN1, with a special focus on non-functioning (nf)-PanNETs. The participants represented a broad range of medical scientists as well as representatives from patient organizations, pharmaceutical industry and research societies. In a case-based approach, participants addressed early detection, surveillance, prognostic factors and management of localized and advanced disease. For each topic, after a review of current evidence, key unmet clinical needs and future research directives to make meaningful progress for MEN1 patients with nf-PanNETs were identified. International multi-institutional collaboration is needed for adequately sized studies and validation of findings in independent datasets. Collaboration between basic, translational and clinical scientists is paramount to establishing a translational science approach. In addition, bringing clinicians, scientists and patients together improves the prioritization of research goals, assures a patient-centered approach and maximizes patient involvement. It was concluded that collaboration, research infrastructure, methodologic and reporting rigor are essential to any translational science effort. The highest priority for nf-PanNETs in MEN1 syndrome are (1) the development of a data and biospecimen collection architecture that is uniform across all MEN1 centers, (2) unified strategies for diagnosis and follow-up of incident and prevalent nf-PanNETs, (3) non-invasive detection of individual nf-PanNETs that have an increased risk of metastasis, (4) chemoprevention clinical trials driven by basic research studies and (5) therapeutic targets for advanced disease based on biologically plausible mechanisms.


Assuntos
Neoplasia Endócrina Múltipla Tipo 1/complicações , Neoplasias Pancreáticas/etiologia , Adulto , Feminino , Humanos , Neoplasias Pancreáticas/patologia
4.
AJNR Am J Neuroradiol ; 40(1): 142-149, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30523145

RESUMO

BACKGROUND AND PURPOSE: Minimally invasive parathyroid surgery relies critically on image guidance, but data comparing the efficacy of various imaging modalities are scarce. Our aim was to perform a blinded comparison of the localizing capability of technetium Tc99m sestamibi SPECT, multiphase multidetector 4D CT, and the combination of these 2 modalities (technetium Tc99m sestamibi SPECT + multiphase multidetector 4D CT). MATERIALS AND METHODS: We reviewed the records of 31 (6 men, 25 women; median age, 56 years) consecutive patients diagnosed with biochemically confirmed primary hyperparathyroidism between November 2009 and March 2010 who underwent preoperative technetium Tc99m sestamibi SPECT and multiphase multidetector 4D CT performed on the same scanner with pathologic confirmation by resection of a single parathyroid adenoma. Accuracy was determined separately for localization to the correct side and quadrant using surgical localization as the standard of reference. RESULTS: Surgical resection identified 14 left and 17 right parathyroid adenomas and 2 left inferior, 12 left superior, 11 right inferior, and 6 right superior parathyroid adenomas. For left/right localization, technetium Tc99m sestamibi SPECT achieved an accuracy of 93.5% (29 of 31), multiphase multidetector 4D CT achieved 96.8% accuracy (30 of 31), and technetium Tc99m sestamibi SPECT + multiphase multidetector 4D CT achieved 96.8% accuracy (30 of 31). For quadrant localization, technetium Tc99m sestamibi SPECT accuracy was 67.7% (21 of 31), multiphase multidetector 4D CT accuracy was 87.1% (27 of 31), and technetium Tc99m sestamibi SPECT + multiphase multidetector 4D CT accuracy was 93.5% (29 of 31). Reader diagnostic confidence was consistently ranked lowest for technetium Tc99m sestamibi SPECT and highest for technetium Tc99m sestamibi SPECT + multiphase multidetector 4D CT. CONCLUSIONS: For left/right localization of parathyroid adenomas, all modalities performed equivalently. For quadrant localization, technetium Tc99m sestamibi SPECT + multiphase multidetector 4D CT is superior to technetium Tc99m sestamibi SPECT.


Assuntos
Adenoma/diagnóstico por imagem , Tomografia Computadorizada Multidetectores/métodos , Neoplasias das Paratireoides/diagnóstico por imagem , Tomografia Computadorizada de Emissão de Fóton Único/métodos , Adenoma/cirurgia , Adulto , Idoso , Feminino , Tomografia Computadorizada Quadridimensional , Humanos , Hiperparatireoidismo Primário/diagnóstico por imagem , Hiperparatireoidismo Primário/etiologia , Processamento de Imagem Assistida por Computador , Masculino , Pessoa de Meia-Idade , Neoplasias das Paratireoides/cirurgia , Compostos Radiofarmacêuticos , Estudos Retrospectivos , Tecnécio Tc 99m Sestamibi
5.
Neurochem Res ; 39(5): 911-21, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24676701

RESUMO

In a previous report, alterations of the serotonin metabolism were previously reported in mice intoxicated with repeated low doses of soman. In order to better understand the effects induced by repeated low-dose exposure to organophosphorus compounds on physiological and behavioural functions, the levels of endogenous monoamines (serotonin and dopamine) in different brain areas in mice intoxicated with sublethal dose of (O-ethyl-S-[2(di-isopropylamino) ethyl] methyl phosphonothioate) (VX) were analysed by HPLC method with electrochemical detection. Animals were injected once a day for three consecutive days with 0.10 LD50 of VX (5 µg/kg, i.p). Neither severe signs of cholinergic toxicity nor pathological changes in brain tissue of exposed animals were observed. Cholinesterase (ChE) activity was only inhibited in plasma (a maximum of 30% inhibition 24 h after the last injection of VX), but remained unchanged in the brain. Serotonin and dopamine (DA) metabolism appeared significantly modified. During the entire period of investigation, at least one of the three parameters investigated (i.e. DA and DOPAC levels and DOPAC/DA ratio) was modified. During the toxic challenge, an increase of the serotonin metabolism was noted in hippocampus (HPC), hypothalamus/thalamus, pons medulla and cerebellum (CER). This increase was maintained 4 weeks after exposure in HPC, pons medulla and CER whereas a decrease in cortex 3 weeks after the toxic challenge was observed. The lack of correlation between brain ChE activity and neurochemical outcomes points out to independent mechanisms. The involvement in possibly long-lasting behavioural disorders is discussed.


Assuntos
Dopamina/metabolismo , Compostos Organotiofosforados/toxicidade , Serotonina/metabolismo , Ácido 3,4-Di-Hidroxifenilacético/metabolismo , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Inibidores da Colinesterase/farmacologia , Colinesterases/sangue , Masculino , Camundongos Endogâmicos BALB C , Compostos Organotiofosforados/administração & dosagem , Soman/toxicidade
6.
Horm Metab Res ; 44(5): 390-9, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22314389

RESUMO

Metastatic pheochromocytomas and paragangliomas are rare and challenging tumors. The tumor burden, combined with excessive catecholamine production, predispose to a broad spectrum of complications that range from spinal cord compression to any organ damage, all of which may lead to decreased quality of life and overall survival. Current therapies include surgery, systemic chemotherapy and radiopharmaceutical agents. Surgery is often a preferred therapy because it may cure or allow a long-term remission in patients with locoregional or isolated resectable distant metastases. Additionally, surgery can palliate symptoms related to tumor burden or catecholamine excess. However, in patients for whom surgery is not an option, systemic chemotherapy and radiopharmaceutical agents are preferred options. Systemic chemotherapy and radiopharmaceutical agents such as 131I-Metaiodobenzylguanidine (131I-MIBG) may cause partial responses or stabilization of disease with better blood pressure control and symptomatic and performance status improvement. However, as these therapies are only palliative, patients' quality of life and personal preferences should always be considered. The recognition of molecular pathways involved in the pheochromocytoma and paraganglioma tumorigenesis has driven the development of new therapeutic options. Agents such as tyrosine kinase, MAPK, PI3K, or hypoxia inducible factor inhibitors, alone or in combination, may represent novel therapeutic strategies that could be evaluated in prospective clinical trials. Transcriptional profiling and the development of personalized cancer medicine will help to pave the way for more specific therapeutic approaches and combinations.


Assuntos
Neoplasias das Glândulas Suprarrenais/terapia , Feocromocitoma/terapia , Neoplasias das Glândulas Suprarrenais/genética , Neoplasias das Glândulas Suprarrenais/radioterapia , Neoplasias das Glândulas Suprarrenais/cirurgia , Animais , Humanos , Terapia de Alvo Molecular , Metástase Neoplásica , Paraganglioma/genética , Paraganglioma/radioterapia , Paraganglioma/cirurgia , Paraganglioma/terapia , Feocromocitoma/genética , Feocromocitoma/radioterapia , Feocromocitoma/cirurgia
7.
Clin Radiol ; 67(1): 38-46, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21783181

RESUMO

AIM: To describe the morphological and contrast-agent washout characteristics of adrenocortical carcinomas (ACCs) on computed tomography (CT). MATERIALS AND METHODS: Forty-one patients with histopathologically proven ACCs were retrospectively evaluated. The morphological characteristics of the ACCs were documented and compared with surgical and histopathological findings. The percentage of contrast agent enhancement washout (PEW) and relative PEW (RPEW) were calculated for 17 patients who had the combination of unenhanced, portal venous, and 15 min delayed phase images. RESULTS: Characteristic imaging findings of ACCs included large size (38 of 41 tumours were >6 cm), well-defined margin with a thin enhancing rim (25 patients), and central stellate area of low attenuation on contrast-enhanced CT images (21 patients). Tumour extension into the inferior vena cava (IVC) with associated thrombus was identified on CT in six (14.6%) patients. Of 17 tumours evaluated, 12 (71%) had a PEW value of ≤60%, and 14 (82%) had an RPEW value of ≤40%. CONCLUSION: Large size, a well-defined margin with a thin enhancing rim, central low attenuation, and a predilection for extension into the IVC are typical morphological characteristics of ACC on CT. The contrast-washout characteristics of ACCs, in concordance with their malignant nature, share those of non-adenomas rather than adenomas.


Assuntos
Neoplasias das Glândulas Suprarrenais/diagnóstico por imagem , Carcinoma Adrenocortical/diagnóstico por imagem , Meios de Contraste , Tomografia Computadorizada por Raios X , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
8.
Hum Exp Toxicol ; 30(6): 491-8, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20534641

RESUMO

Using the hairless mouse screening model presented in the companion paper(1) the aim of this study was to assess two skin decontaminating systems: Fuller's earth (FE) and Reactive Skin Decontamination Lotion (RSDL) against two extremely toxic chemical warfare agents that represent a special percutaneous hazard, sulphur mustard (SM) and O-ethyl-S-(2[di-isopropylamino]ethyl)methyl-phosphonothioate (VX). Five minutes after being exposed on the back to either 2 µL of neat sulphur mustard or 50 µg.kg(-1) of diluted VX, mice were decontaminated. Both systems were able to reduce blisters 3 days after SM exposure. However, RSDL was found to be more efficient than FE in reducing the necrosis of the epidermis and erosion. In the case of VX exposure, RSDL, whatever the ratio of decontaminant to toxicant used (RSDL 10, 20, 50), was not able to sufficiently prevent the inhibition of plasma cholinesterases taken as a surrogate marker of exposure and toxicity. Only FE reduced significantly the ChE inhibition. Some of these observations are different from our previous results obtained in domestic swine and these changes are thus discussed in the perspective of using SKH-1 hairless mice for the initial in vivo screening of decontaminants.


Assuntos
Compostos de Alumínio/administração & dosagem , Substâncias para a Guerra Química/toxicidade , Descontaminação , Diacetil/análogos & derivados , Compostos de Magnésio/administração & dosagem , Gás de Mostarda/toxicidade , Compostos Organotiofosforados/toxicidade , Polietilenoglicóis/administração & dosagem , Silicatos/administração & dosagem , Animais , Inibidores da Colinesterase/administração & dosagem , Diacetil/administração & dosagem , Modelos Animais de Doenças , Masculino , Camundongos , Camundongos Pelados , Pele/efeitos dos fármacos , Pele/patologia
9.
J Clin Endocrinol Metab ; 95(5): 2023-37, 2010 May.
Artigo em Inglês | MEDLINE | ID: mdl-20215394

RESUMO

CONTEXT: Pheochromocytomas and paragangliomas (PHEO/PGL) are neuroendocrine tumors that arise from sympathetic and parasympathetic paraganglia. Diagnosed rarely during childhood, PHEO/PGL are nonetheless important clinical entities, particularly given our evolving understanding of their pathophysiology. EVIDENCE ACQUISITION: We identified articles through the U.S. National Library of Medicine by using the search terms pheochromocytoma and paraganglioma. Results were narrowed to manuscripts that included children and studies related to the genetics of PHEO/PGL. Web-based resources for genetic disorders were also used. For all articles, we performed subsequent reference searches and verification of source data. EVIDENCE SYNTHESIS: Up to 20% of PHEO/PGL are diagnosed in children. Most are functional tumors, and clinical presentation includes symptoms related to catecholamine hypersecretion and/or tumor mass effect. Increasingly, PHEO/PGL are identified during presymptomatic screening in children with genetic syndromes associated with PHEO/PGL (multiple endocrine neoplasia type 2, von Hippel-Lindau disease, and the paraganglioma syndromes). Plasma and/or urine metanephrines are the best diagnostic test for a functional tumor, and the management of pediatric patients is similar to adults. Genetic counseling should be undertaken in all cases. Although most pediatric PHEO/PGL are benign, these tumors can occasionally metastasize, a condition for which no curative treatment exists. CONCLUSIONS: Although PHEO/PGL are rarely diagnosed during childhood, the pediatric provider should be able to recognize and screen for such tumors, particularly in the context of a known genetic predisposition. Optimal care of these children includes a multidisciplinary team approach at centers experienced in the evaluation and treatment of these uncommon yet fascinating endocrine neoplasms.


Assuntos
Paraganglioma/etiologia , Feocromocitoma/etiologia , Criança , Dopamina/metabolismo , Aconselhamento Genético , Humanos , Mutação de Sentido Incorreto , Paraganglioma/diagnóstico por imagem , Paraganglioma/tratamento farmacológico , Paraganglioma/genética , Paraganglioma/terapia , Feocromocitoma/diagnóstico , Feocromocitoma/diagnóstico por imagem , Feocromocitoma/genética , Feocromocitoma/terapia , Radiografia , Proteína Supressora de Tumor Von Hippel-Lindau/genética
10.
Br J Surg ; 95(8): 957-60, 2008 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-18574846

RESUMO

BACKGROUND: Primary hyperparathyroidism (PHPT) with coexisting thyroid disease has been considered a contraindication to minimally invasive parathyroidectomy (MIP). This study assessed the impact of thyroid ultrasonography and guided fine-needle aspiration (FNA) biopsy with cytological review of the aspiration in distinguishing patients eligible for MIP from those requiring open parathyroidectomy with thyroid surgery. METHODS: The records of 194 consecutive patients who had minimally invasive or open parathyroidectomy for sporadic PHPT were reviewed retrospectively. Thyroid ultrasonographic findings and FNA results were compared with surgical and pathology records. RESULTS: A total of 163 patients (84.0 per cent) were eligible for MIP based on ultrasonographic findings with or without FNA results. Ultrasonography detected concurrent thyroid disease in 163 patients (84.0 per cent). Thirty-nine (23.9 per cent) underwent FNA, of whom 16 had benign findings and were eligible for MIP; the remaining 23 had suspicious FNA results and had open parathyroidectomy combined with thyroid surgery. Postoperative thyroid histopathology confirmed malignancy in nine patients, eight of whom had disease detected ultrasonographically. Micronodular thyroid disease (less than 1 cm) accounted for four of nine malignancies. CONCLUSION: Most patients with PHPT are eligible for MIP. Experienced ultrasonographers can diagnose coexisting micronodular and macronodular thyroid disease, and identify patients eligible for MIP.


Assuntos
Hiperparatireoidismo Primário/cirurgia , Paratireoidectomia , Cuidados Pré-Operatórios/métodos , Doenças da Glândula Tireoide/diagnóstico por imagem , Tireoidectomia/métodos , Ultrassonografia de Intervenção , Biópsia por Agulha Fina , Contraindicações , Humanos , Hiperparatireoidismo Primário/complicações , Hiperparatireoidismo Primário/diagnóstico por imagem , Hiperparatireoidismo Primário/patologia , Estudos Retrospectivos , Doenças da Glândula Tireoide/complicações , Doenças da Glândula Tireoide/patologia
11.
Neurochem Res ; 33(5): 919-26, 2008 May.
Artigo em Inglês | MEDLINE | ID: mdl-17994275

RESUMO

In order to better understand the effects of repeated low-dose exposure to organophosphorus (OPs) on physiological and behavioural functions, we analysed the levels of endogenous monoamines (serotonin and dopamine) in different brain areas after repeated exposure of mice to sublethal dose of soman. Animals were injected once a day for 3 days with 0.12 LD50 of soman (47 microg/kg, i.p.). They did not show either severe signs of cholinergic toxicity or pathological changes in brain tissue. 24 h after the last injection of soman, inhibition of cholinesterase was similar in plasma and brain (32% and 37% of inhibition respectively). Afterwards, recovery of cholinesterase activity was faster in the plasma than in the brain. Dopamine levels were not significantly modified. On the other hand, we observed a significant modification of the serotoninergic system. An increase of the 5-HIAA/5-HT ratio was maintained for 2 and 4 weeks after exposure in the hippocampus and the striatum respectively. This study provides the first evidence of a modification of the 5-HT turnover in the hippocampus and the striatum after repeated low-dose intoxication with a nerve agent. Further experiments are necessary to evaluate the relationship between these modifications and the unexpected neuropsychological disorders usually reported after chronic exposure of organophosphorus.


Assuntos
Monoaminas Biogênicas/metabolismo , Encéfalo/efeitos dos fármacos , Inibidores da Colinesterase/toxicidade , Soman/toxicidade , Animais , Encéfalo/metabolismo , Inibidores da Colinesterase/administração & dosagem , Relação Dose-Resposta a Droga , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Soman/administração & dosagem
12.
New Phytol ; 171(4): 751-7, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-16918546

RESUMO

Little is known about the spatial distribution of excess manganese (Mn) in the leaves of tolerant plants. Recently, the first such study of a Mn hyperaccumulator showed that the highest localized Mn concentrations occur in the photosynthetic tissue. This is in contrast to reports based on localization of foliar accumulation of other heavy metals. Here, four tree species, Gossia bidwillii, Virotia neurophylla, Macadamia integrifolia and Macadamia tetraphylla, which hyperaccumulate or strongly accumulate Mn, were studied. Cross-sectional foliar Mn localization was carried out in situ using proton-induced X-ray emission/energy dispersive X-ray analysis (PIXE/EDAX). All four species contained photosynthetic tissues with multiple palisade layers. These were shown to be the primary sequestration sites for Mn. Mn was not detected in the epidermal tissues. The findings of this study demonstrate a concurrence of three traits in four tree species, that is, accumulation of excess Mn in the leaves, its primary sequestration in the photosynthetic tissues, and multiple-layer palisade mesophyll.


Assuntos
Microanálise por Sonda Eletrônica/métodos , Manganês/metabolismo , Folhas de Planta/metabolismo , Árvores/metabolismo , Folhas de Planta/citologia
13.
Br J Surg ; 90(6): 755-8, 2003 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-12808628

RESUMO

BACKGROUND: Fine-needle aspiration cytology (FNAC) is useful for selecting patients with thyroid nodules for thyroidectomy. Its value in patients who have been exposed to low-dose therapeutic radiation is questionable because these patients have an increased risk of multifocal benign and malignant tumours, and thyroid cancer is common in such patients. METHODS: Between 1960 and 1999, 171 patients with one or more thyroid nodules who had a history of exposure to radiation underwent operation; 49 of these patients had preoperative FNAC. The cytology results in these 49 patients were compared with those of an age- and sex-matched control group of patients with thyroid nodules who did not have a history of radiation exposure. RESULTS: Of those who had been exposed to radiation, six of 20 patients with 'benign' cytology by FNAC and six of 16 patients with 'suspicious' cytology had thyroid cancer. All 13 specimens considered to be malignant on FNAC were indeed malignant. There was a higher rate of false-negative cytological examinations among patients with a history of irradiation that in those without. CONCLUSION: FNAC of thyroid nodules in patients with a history of irradiation is not as accurate as that in non-irradiated patients, primarily because of coexisting occult thyroid cancers.


Assuntos
Biópsia por Agulha/normas , Carcinoma Papilar/diagnóstico , Neoplasias Induzidas por Radiação/diagnóstico , Neoplasias da Glândula Tireoide/diagnóstico , Biópsia por Agulha/métodos , Carcinoma Papilar/cirurgia , Humanos , Neoplasias Induzidas por Radiação/cirurgia , Valor Preditivo dos Testes , Sensibilidade e Especificidade , Neoplasias da Glândula Tireoide/cirurgia , Nódulo da Glândula Tireoide/diagnóstico , Nódulo da Glândula Tireoide/cirurgia , Tireoidectomia/métodos
14.
Nat Genet ; 32(4): 676-80, 2002 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-12434154

RESUMO

We report here the identification of a gene associated with the hyperparathyroidism-jaw tumor (HPT-JT) syndrome. A single locus associated with HPT-JT (HRPT2) was previously mapped to chromosomal region 1q25-q32. We refined this region to a critical interval of 12 cM by genotyping in 26 affected kindreds. Using a positional candidate approach, we identified thirteen different heterozygous, germline, inactivating mutations in a single gene in fourteen families with HPT-JT. The proposed role of HRPT2 as a tumor suppressor was supported by mutation screening in 48 parathyroid adenomas with cystic features, which identified three somatic inactivating mutations, all located in exon 1. None of these mutations were detected in normal controls, and all were predicted to cause deficient or impaired protein function. HRPT2 is a ubiquitously expressed, evolutionarily conserved gene encoding a predicted protein of 531 amino acids, for which we propose the name parafibromin. Our findings suggest that HRPT2 is a tumor-suppressor gene, the inactivation of which is directly involved in predisposition to HPT-JT and in development of some sporadic parathyroid tumors.


Assuntos
Adenoma/genética , Predisposição Genética para Doença , Mutação em Linhagem Germinativa , Hiperparatireoidismo/genética , Neoplasias das Paratireoides/genética , Proteínas/genética , Adenoma/patologia , Sequência de Aminoácidos , Sequência de Bases , Cromossomos Humanos Par 1 , Éxons , Etiquetas de Sequências Expressas , Genes Supressores de Tumor , Ligação Genética , Testes Genéticos , Genótipo , Heterozigoto , Humanos , Repetições de Microssatélites , Dados de Sequência Molecular , Fases de Leitura Aberta , Neoplasias das Paratireoides/química , Neoplasias das Paratireoides/patologia , Linhagem , Proteínas/química , Síndrome , Proteínas Supressoras de Tumor
16.
Am Surg ; 67(6): 582-4, 2001 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-11409808

RESUMO

Positron emission tomography (PET) scanning is an emerging technology with substantial implications for patients with solid tumors. PET is useful in identifying sites of metastatic disease as well as primary malignancy and evaluating suspicious findings found via other imaging modalities. PET is becoming a standard modality for metastatic evaluation of a variety of malignancies. However, this imaging is not limited by histology and may reveal clinically occult second lesions. We present five cases of a clinically occult thyroid cancer found in patients who underwent PET scanning for metastatic evaluations. The principal diagnoses included two patients with malignant melanoma, one each with gastric, rectal, and colonic adenocarcinoma. None of the cases had findings on physical examination. Increased uptake in the region of the thyroid was evident on the PET scan, and fine-needle aspiration biopsy indicated papillary carcinoma of the thyroid in all five cases. Although evaluation of metastatic disease is the primary purpose for PET in this setting the discovery of occult thyroid malignancy is an additional benefit of such imaging. This emphasizes the importance of investigating suspicious areas found by PET and not simply assuming that these are all sites of metastatic disease. Furthermore incidental findings of uptake in the region of the thyroid make consideration of a primary carcinoma mandatory.


Assuntos
Carcinoma Papilar/diagnóstico por imagem , Neoplasias Primárias Múltiplas/diagnóstico por imagem , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Idoso , Biópsia por Agulha , Carcinoma Papilar/patologia , Carcinoma Papilar/cirurgia , Feminino , Humanos , Fígado/diagnóstico por imagem , Pulmão/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica/diagnóstico por imagem , Neoplasias Primárias Múltiplas/patologia , Neoplasias Primárias Múltiplas/cirurgia , Estudos Retrospectivos , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/cirurgia , Tireoidectomia , Tomografia Computadorizada de Emissão
17.
World J Surg ; 24(11): 1319-22, 2000 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-11038200

RESUMO

Most people would agree that successful parathyroidectomy depends on two important variables: the surgeon's recognition and excision of the abnormal parathyroid gland(s) and the pathologist's confirmation that the removed tissue is parathyroid tissue. Frozen section is usually employed to confirm the identity of parathyroid tissue, but occasionally confirmation cannot be made without a permanent section, as with intrathyroidal glands. This study proposes a new method of expeditious and easy confirmation of parathyroid tissue utilizing the immunoassay for quick measurement of intraoperative parathyroid hormone (IOPTH). By directly aspirating the suspected adenoma, the assay becomes a rapid diagnostic tool that can be used as an alternative to frozen section. In cases where the surgeon is already planning to employ the assay, the elimination of frozen section is cost-effective. Intraoperative aspiration of histologically confirmed parathyroid adenomas was performed on 12 consecutive patients undergoing parathyroid surgery. Parathyroid glands were aspirated with a 22-gauge syringe after gland excision. Aspirates were placed in 1 to 3 ml of buffered saline. A similar process was performed on 12 thyroid controls. Specimens were centrifuged, aliquotted, and stored at -70 degrees C. The parathyroid hormone value was analyzed electively by rapid assay and the values recorded. For all parathyroid aspirates, the rapid assay value was > 1500 pg/ml, exceeding the uppermost limit of the diagnostic chart. Values for thyroid aspirates ranged from 58 to 85 pg/ml (mean 75.7 pg/ml). In all cases tissue confirmation was achieved with permanent section. Values were 100% sensitive and specific. Measurement of PTH from intraoperative aspiration of suspected parathyroid adenomas is clinically useful in patients for whom frozen section would routinely be employed. Values > 1500 pg/ml secure the tissue diagnosis. There is no additional cost in cases where IOPTH monitoring is already being utilized to confirm cure. The elimination of frozen section could be cost-effective and, for some institutions, actually decrease the operating time as the IOPTH assay takes only 15 minutes. PTH assay is an accurate diagnostic technique and to date is 100% sensitive and specific for differentiating between parathyroid tumors and thyroid nodules.


Assuntos
Biópsia por Agulha/métodos , Criopreservação , Hormônio Paratireóideo/análise , Neoplasias das Paratireoides/patologia , Neoplasias das Paratireoides/cirurgia , Feminino , Humanos , Masculino , Monitorização Intraoperatória/métodos , Paratireoidectomia/métodos , Sensibilidade e Especificidade
18.
Crit Care Med ; 28(8): 3071-4, 2000 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-10966298

RESUMO

OBJECTIVE: To report an adult trauma patient fatality related to propofol administration. DESIGN: Retrospective case review. SETTING: Trauma intensive care unit (ICU) in a level one trauma center. PATIENT: An 18-yr-old man involved in a motor vehicle crash. INTERVENTIONS: Treatment for multiple trauma injuries and propofol sedation. MEASUREMENTS AND MAIN RESULTS: Posttrauma ICU monitoring was performed. The patient developed cardiac arrhythmia, metabolic acidosis, and cardiac failure, which resulted in death. CONCLUSION: Death related to propofol infusion can occur in adults as well as in pediatric patients.


Assuntos
Acidose/induzido quimicamente , Arritmias Cardíacas/induzido quimicamente , Insuficiência Cardíaca/induzido quimicamente , Propofol/efeitos adversos , Adolescente , Evolução Fatal , Humanos , Masculino , Estudos Retrospectivos
19.
Clin Positron Imaging ; 3(4): 149, 2000 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-11150752

RESUMO

Purpose: To examine one potential clinical application of dedicated devices for positron emission mammography.Background: Dedicated devices for breast imaging with FDG have technical specifications that appear well-suited for detecting small breast cancers, including registration with x-rays, high count sensitivity, and spatial resolution in the 2-3 mm range.Methods: In IRB-approved clinical trials, patients who were scheduled for biopsy for suspicious findings on x-ray mammograms were injected with 10-20 mCi FDG intravenously one to two hours prior to x-ray guided core biopsy or lumpectomy. Positron emission mammograms using a dedicated device were performed just before biopsy, and results compared to final histopathology.Results: Three patients whose cancers were missed on initial x-ray mammograms or whose mammograms contained subtle abnormalities that were not strongly suspicious for cancer, were shown to have very suspicious hot spots on positron emission mammograms. These patients were later confirmed to have cancer.Discussion: The role for dedicated devices for positron emission mammography is evolving. Finding cancers that are either mammographically occult or have low indices of suspicion is a potential application for this technique. Further clinical and technical work will be needed to better define the strengths and weaknesses of the device in this application.

20.
Surgery ; 126(6): 1063-8; discussion 1069, 1999 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-10598189

RESUMO

BACKGROUND: The histologic criteria to classify follicular thyroid neoplasms are controversial. Criteria used for diagnosis and treatment varies both within and between specialty groups. This discordance makes it difficult to compare disease and management practice. This is especially problematic in issues concerning reoperations and survival. To determine the degree of disparity, we surveyed 3 groups of specialists. METHODS: A questionnaire describing 10 histologic scenarios was sent to an equal number of thyroidologists, endocrine surgeons, and endocrine pathologists. Individuals were randomly selected from rosters of 3 corresponding societies. Each item asked for a rating of a diagnosis and treatment. Questionnaires were distributed and received by facsimile, and responses were kept confidential. The response rate was 60%. RESULTS: Responses were analyzed by nonparametric statistical tests. Two scenarios had significant disagreement among specialties in both diagnosis and treatment: one scenario involved the assessment of neoplasms with minimal capsular invasion; the other scenario involved Hürthle cell features. In both scenarios pathologists tended to be more conservative in assigning the term carcinoma and recommending total thyroidectomy. Significant disagreement within specialty groups was also noted. Two other scenarios dealt with the distinction between minimally and widely invasive carcinoma; significantly, pathologists viewed tumors as less invasive. CONCLUSIONS: This study indicates that much disparity exists among specialists in pathology, endocrinology, and surgery and among experts in each of these disciplines. It highlights that there is no uniform classification. If multicenter trials to evaluate treatment options are to occur, a universal classification must be accepted.


Assuntos
Adenocarcinoma Folicular/classificação , Adenocarcinoma Folicular/terapia , Medicina/normas , Especialização , Neoplasias da Glândula Tireoide/classificação , Neoplasias da Glândula Tireoide/terapia , Adenocarcinoma Folicular/cirurgia , Coleta de Dados , Tomada de Decisões , Endocrinologia/normas , Cirurgia Geral/normas , Humanos , Patologia/normas , Inquéritos e Questionários , Neoplasias da Glândula Tireoide/cirurgia
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