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1.
Sci Total Environ ; 746: 141200, 2020 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-32771760

RESUMO

The continuous release of pharmaceuticals from WWTP effluents to freshwater is a matter of concern, due to their potential effects on non-target organisms. The occurrence of pharmaceuticals in WWTPs and their associated hazard have been scarcely studied in Latin American countries. This study aimed at monitoring for the first time the occurrence of 70 pharmaceutical active compounds (PhACs) in WWTPs across Costa Rica; the application of the hazard quotient (HQ) approach coupled to ecotoxicological determinations permitted to identify the hazard posed by specific pharmaceuticals and toxicity of the effluents, respectively. Thirty-three PhACs were found, with 1,7-dimethylxanthine, caffeine, acetaminophen, ibuprofen, naproxen, ketoprofen and gemfibrozil being the most frequently detected (influents/effluents). HQ for specific pharmaceuticals revealed 24 compounds with high/medium hazard in influents, while the amount only decreased to 21 in effluents. The top HQ values were obtained for risperidone, lovastatin, diphenhydramine and fluoxetine (influent/effluent samples), plus caffeine (influent) and trimethoprim (effluent). Likewise, the estimation of overall hazard in WWTP samples (sum of individual HQ, ∑HQ) demonstrated that every influent and 96% of the effluents presented high hazard towards aquatic organisms. Ecotoxicological analysis (Daphnia magna, Lactuca sativa and Microtox test) revealed that 16.7% of the effluents presented toxicity towards all benchmark organisms; the phytotoxicity was particularly frequent, as inhibition values ≥20% in the germination index for L. sativa were obtained for all the effluents. The ∑HQ approach estimated the highest hazard in urban wastewater, while the ecotoxicological results showed the highest toxicity in hospital and landfill wastewater. Likewise, ecotoxicological results and ∑HQ values showed a rather poor correlation; instead, better correlations were obtained between ecotoxicological parameters and HQ values for some individual pharmaceuticals such as cephalexin and diphenhydramine. Findings from this study provide novel information on the occurrence of pharmaceuticals and the performance of WWTPs in the tropical region of Central America.

2.
Integr Comp Biol ; 2020 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-32386301

RESUMO

The field of comparative biomechanics strives to understand the diversity of the biological world through the lens of physics. To accomplish this, researchers apply a variety of modelling approaches to explore the evolution of form and function ranging from basic lever models to intricate computer simulations. While advances in technology have allowed for increasing model complexity, great insight can still be gained through the use of low-parameter 'simple' models. All models, regardless of complexity, are simplifications of reality and must make assumptions; 'simple' models just make more assumptions than complex ones. However, 'simple' models have several advantages. They allow individual parameters to be isolated and tested systematically, can be made applicable to a wide range of organisms and make good starting points for comparative studies, allowing for complexity to be added as needed. To illustrate these ideas, we perform a case study on body form and center of mass stability in ants. Ants show a wide diversity of body forms, particularly in terms of the relative size of the head, petiole(s) and gaster (the latter two make-up the segments of the abdomen not fused to thorax in hymenopterans). We use a 'simple' model to explore whether balance issues pertaining to the center of mass influence patterns of segment expansion across major ant clades. Results from phylogenetic comparative methods imply that the location of the center of mass in an ant's body is under stabilizing selection, constraining the center of mass to the middle segment (thorax) over the legs. This is potentially maintained by higher correlated rates of evolution between the head and gaster on either end. While these patterns arise from a model which makes several assumptions/simplifications relating to shape and materials, they still offer intriguing insights into the body plan of ants across ∼75% of their diversity. The results from our case study illustrate how 'simple', low-parameter models both highlight fundamental biomechanical trends, and aid in crystalizing specific questions and hypotheses for more complex models to address.

3.
Head Neck Pathol ; 2020 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-32410132

RESUMO

Well-differentiated (WDL) and dedifferentiated liposarcomas (DL) of the pharynx, larynx and oral cavity are rare, often mimicking benign lipomatous neoplasms or non-lipogenic mesenchymal tumors. Cases of WDL/DL arising in the upper aerodigestive tract, exclusive of the cervical esophagus, were reviewed. Morphologic features, ancillary studies, including fluorescence in situ hybridization (FISH) studies for CPM/MDM2, and clinical data was catalogued. Eight WDL/DL (4 WDL, 4 DL); were identified in patients ranging from 32 to 77 years (median 52.5 years; 6 males, 2 females) with sites of origin including hypopharynx (5 cases), larynx (2 cases) and oral cavity (1 case). Six of the 8 cases were received for expert consultation, and the remaining 2 cases were initially misdiagnosed as benign lymphangiomatous or fibroepithelial polyps. Morphologically, 4 tumors had areas mimicking various non-lipomatous soft tissue tumors including nodular fasciitis, mammary-type myofibroblastoma, low-grade myofibroblastic sarcoma and undifferentiated pleomorphic sarcoma, 2 cases simulated benign hypopharyngeal polyps, and 1 lesion was notable for a dense lymphoplasmacytic infiltrate suggestive of hematolymphoid neoplasm or IgG4-related sclerosing disease. FISH showed amplification of CPM/MDM2 (8/8 cases). All cases (4/4) with longer than 1-year of follow-up recurred (45-118 months) with 1 tumor showing progression to DL. WDL/DL presenting in the upper aerodigestive tract are rare and diagnostically challenging. Awareness of the morphologic spectrum of WDL/DL coupled with appropriate use of MDM2 FISH is essential for accurate classification and management, as these tumors appear to have a high risk for local recurrence and eventual dedifferentiation in these anatomical locations.

4.
Head Neck Pathol ; 2020 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-32350809

RESUMO

Salivary duct carcinoma (SDC) commonly expresses androgen receptor (AR) and HER2, giving rise to treatment implications. SDC may also express programmed-death-ligand-1 (PD-L1), a predictive marker of response to checkpoint inhibitors. PD-L1 can be associated with genomic instability and high density of tumor infiltrating lymphocytes (TILs). Evaluation of HER2 immunohistochemistry (IHC) in SDC is not standardized, and relationships between ERBB2 copy numbers, PD-L1 expression and TILs in SDC are unknown. We evaluated 32 SDCs for HER2, AR and PD-L1 expression (IHC), ERBB2 status (FISH) and TILs (slide review). HER2 was scored with three different systems (breast, gastric, proposed salivary gland). PD-L1 was evaluated with the combined positive score. Most patients were older men, presenting at advanced clinical stage with nodal or distant metastases. During follow-up (mean 5 years, range 6 months to 21 years), 25 of the 32 patients (78%) died of SDC. We propose a HER2 IHC scoring system which accurately predicts underlying ERBB2 amplification or increased copy numbers in SDC. Most tumors had increased ERBB2 copy numbers (19/32 amplification, 6/32 aneusomy), a finding associated with higher TIL densities (p = 0.045) and PD-L1 expression (p = 0.025). Patients with TILs ≥ 40% had better prognoses (Log-Rank p = 0.013), with TILs being favorable prognosticators in univariate analysis (Hazard ratio: 0.18, p = 0.024). A subset of SDCs with increased ERBB2 copy numbers have higher TILs and PD-L1 expression. TILs ≥ 40% are associated with better prognosis.

5.
Thyroid ; 29(11): 1615-1622, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31595822

RESUMO

Background: Anaplastic thyroid cancer (ATC) has poor prognosis with median overall survival (OS) of ∼6 months. We previously reported high PD-1/PDL-1 staining in ATC, raising the possibility of the productive application of the immunotherapeutic pembrolizumab. However, having found pembrolizumab to anecdotally have limited single-agent activity in ATC, we sought to alternatively define whether pembrolizumab might synergistically combine with chemoradiotherapy as initial ATC therapy. Methods: An investigator-initiated therapeutic phase 2 trial of pembrolizumab, 200 mg intravenously (IV) every 3 weeks, combined with chemoradiotherapy (docetaxel/doxorubicin, 20 mg/m2 each IV weekly plus volumetric modulated arc therapy) was initiated as frontline therapy (with or without surgery) in ATC to assess efficacy and toxicities. Six-month OS was selected as the primary endpoint using a Simon's optimal design with interim analysis (targeting accrual of 25 patients; Cohort A: prior resection, Cohort B: no resection). Based on a prior patient cohort-treated similarly, but without pembrolizumab, the design was such that, if 6-month true survival is 75%, the probability of declaring the approach worthy of further pursuit would be 91%. Results: Three patients were enrolled, two with rapidly enlarging unresectable neck masses. Early tumor responses were favorable in all three, and all three satisfactorily completed: intended radiotherapy, preceding and radiotherapy-concurrent pembrolizumab, and concurrent chemoradiotherapy. However, all three patients died <6 months following therapy initiation-one from pulmonary metastases and two from otherwise unexpected fatal pulmonary complications occurring subsequent to chemoradiotherapy completion-prompting study closure. Conclusions: Although initially tolerated and effective in terms of locoregional disease control, disappointing survival outcomes compared with historical controls raise uncertainty that the piloted approach merits further pursuit in ATC.

6.
Am J Clin Pathol ; 152(4): 502-511, 2019 09 09.
Artigo em Inglês | MEDLINE | ID: mdl-31305880

RESUMO

OBJECTIVES: Long-term follow-up is important for determining performance characteristics of thyroid fine-needle aspiration (FNA). METHODS: Histologic or 3 or more years of clinical follow-up was used to calculate performance characteristics of thyroid FNA before and after implementation of The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC). The impact of noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) classification was also investigated. RESULTS: Follow-up was obtained for 1,277/1,134 and 1,616/1,393 aspirates/patients (median clinical follow-up, 9.9 and 4.4 years, pre- and post-TBSRTC, respectively). Nondiagnostic, suspicious for follicular neoplasm, and suspicious for malignancy (SFM) diagnoses decreased and benign diagnoses increased post-TBSRTC, while atypical rate remained less than 1%. Negative predictive value for benign nodules and positive predictive value (PPV) for SFM increased significantly. Eleven nodules were reclassified as NIFTP, slightly decreasing PPV/risk of malignancy (ROM). CONCLUSIONS: Appropriate ROM for thyroid FNA can be achieved through application of TBSRTC terminology with minimal use of atypical category.


Assuntos
Adenocarcinoma Folicular/patologia , Câncer Papilífero da Tireoide/patologia , Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/patologia , Adulto , Idoso , Biópsia por Agulha Fina , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade
7.
J Environ Sci Health B ; 54(1): 54-60, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30460875

RESUMO

We report on the rates of decomposition of a group of N-methylcarbamate (NMC) pesticides (carbaryl, carbofuran and propoxur) under pre-determined tropical field conditions. Rates of decomposition for three NMCs were determined at pH 7.08 and T = 20 °C and pH 7.70 and T = 33 °C respectively, as follows: carbaryl (78 days and 69 days); carbofuran (143 days and 83 days) and propoxur (116 days and 79 days). Investigation on methods for removal of NMCs and their phenolic decomposition products shows that activated charcoal outperforms zeolite, alumina, diatomaceous earth, cellulose and montmorillonite clay in the removal of both NMCs and phenols from aqueous solution. Furthermore, metal complexation studies on the NMCs and phenols showed that Fe (III) forms a complex with isopropoxyphenol (IPP) within which the Fe:IPP ratio is 1:3, indicative of the formation of a metal chelate complex with the formula Fe(IPP)3.


Assuntos
Carbamatos/química , Metais/química , Praguicidas/química , Praguicidas/isolamento & purificação , Bentonita/química , Biodegradação Ambiental , Carbaril/química , Carbaril/isolamento & purificação , Carbofurano/química , Carbofurano/isolamento & purificação , Celulose/química , Argila/química , Hidrólise , Fenóis/química , Propoxur/química , Propoxur/isolamento & purificação , Soluções/química , Clima Tropical , Poluentes Químicos da Água/química , Poluentes Químicos da Água/isolamento & purificação , Zeolitas/química
8.
Head Neck ; 41(5): 1335-1341, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30536472

RESUMO

BACKGROUND: Past research established that surgery plus adjuvant radiotherapy (S + AR) improves overall survival (OS) in esthesioneuroblastoma (ENB). However, it is unknown if the addition of adjuvant chemotherapy (AC) further improves survival. The primary objective of this study was to compare survival among patients treated with S + AR alone to patients who underwent S + AR + AC. METHODS: Retrospective review of patient records. RESULTS: Thirty-eight patients met inclusion criteria for either S + AR or S + AR + AC treatment groups. The S + AR + AC group contained more patients with Kadish stage D disease, dural invasion, and positive histologic margins postsurgery. All S + AR + AC patients received platinum-based regimens, combined with etoposide in 67%. OS and recurrence-free survival did not differ between the two groups, even when restricting the analysis to patients with Kadish stages B and C disease. CONCLUSION: Patients who received platinum-based AC did not exhibit improved survival compared to S + AR alone. Further investigation, preferably prospective, into the optimal use of systemic therapy in ENB is warranted.

9.
Otol Neurotol ; 39(8): e712-e721, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30001283

RESUMO

OBJECTIVE: To date, less than 150 cases of middle ear adenomatous neuroendocrine tumors (MEANTs) have been reported in the English literature. The objective of this study was to provide a contemporary analysis of these rare lesions and develop a consensus-driven staging system. STUDY DESIGN: Multi-institutional retrospective histopathologic, radiologic, and clinical review. SETTING: Six tertiary referral centers. PATIENTS: Thirty-two patients with pathologically confirmed MEANT. INTERVENTION: Surgical resection, adjuvant therapy. MAIN OUTCOME MEASURES: Clinical manifestations, outcomes, staging system. RESULTS: Patients commonly presented with progressive conductive or mixed hearing loss (90%), aural fullness (50%), and tonal tinnitus (46%). Pulsatile tinnitus (16%), carcinoid syndrome (4%), and facial nerve paresis (4%) were less commonly observed. MEANTs frequently mimicked temporal bone paraganglioma (31%) and cholesteatoma (15%) at presentation. According to a novel T/N/M/S staging system (S = secretory tumor) proposed herein, there were 6 (19%) T1, 19 (59%) T2, and 7 (22%) T3 MEANTs. T3 tumors were significantly more likely to undergo subtotal or near total resection compared with lower staged tumors secondary to adherence to critical neurovascular structures such as the petrous internal carotid artery and facial nerve (p = 0.027). Patients with T3 MEANTs were more likely to experience multiple recurrences, require adjuvant therapy with a somatostatin analogue, or develop permanent facial nerve paresis compared with lower staged tumors. At last follow up, no patients with T1 MEANTs had developed recurrence, whereas 37% (7/19) of patients with T2 MEANT and 57% (4/7) of patients with T3 MEANT experienced either disease recurrence after gross total resection (GTR) or regrowth of known residual tumor requiring additional surgery at a median duration of 72 months (95% CI, 24-84). CONCLUSIONS: Patients with MEANTs can present with nonspecific symptomatology that overlaps with more commonly encountered middle ear lesions. MEANT exhibits a proclivity for recurrence according to T-stage and long-term clinical follow up is necessary, particularly for advanced stage tumors.


Assuntos
Adenoma/patologia , Neoplasias da Orelha/patologia , Orelha Média/patologia , Tumores Neuroendócrinos/patologia , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasia Residual/patologia , Estudos Retrospectivos , Adulto Jovem
10.
Horm Res Paediatr ; 90(1): 8-18, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29804118

RESUMO

BACKGROUND/AIMS: Adrenocortical carcinoma (ACC) is an aggressive childhood cancer. Limited evidence exists on a definite histopathological criterion to differentiate ACC from adrenocortical adenoma. The aim of this study was to investigate the clinicopathological data of children with ACC, identify prognostic factors, and validate a histopathological criterion to differentiate ACC from adrenocortical adenoma. METHODS: This retrospective cohort included 41 children, followed at the Mayo Clinic from 1950 to 2017 (onset of symptoms ≤21 years). Outcomes of interest were: alive with no evidence of disease, alive with evidence of disease, and dead of disease. RESULTS: Median age at onset of symptoms was 15.7 years (n = 41; range, 0.2-21 years). Female:male ratio was 3.6: 1. Mixed symptomatology (> 1 hormone abnormality) was the most common presentation (54%, n = 22). Sixty-six percent of patients (n = 27 out of 41) underwent total adrenalectomy. Metastatic disease was more common in children aged > 12 years (p = 0.002 compared to < 4 years). The most common sites of metastases were the liver and lungs. Overall 2-year and 5-year survival rates were 61% (95% CI 45-77) and 46% (95% CI 30-62), respectively. Metastasis at the time of diagnosis was independently associated with poor prognosis (risk ratio 13.7%; 95% CI 3.9-87.7). Weiss criteria (29%) and modified Weiss criteria (33%) were less accurate in younger patients (< 12 years), compared to the Wieneke index (100%). CONCLUSION: The presence of metastases was an independent prognostic factor. The Wieneke index was the most accurate in predicting clinical outcomes in younger children.


Assuntos
Neoplasias do Córtex Suprarrenal/mortalidade , Carcinoma Adrenocortical/mortalidade , Adolescente , Neoplasias do Córtex Suprarrenal/diagnóstico , Neoplasias do Córtex Suprarrenal/patologia , Neoplasias do Córtex Suprarrenal/terapia , Carcinoma Adrenocortical/diagnóstico , Carcinoma Adrenocortical/patologia , Carcinoma Adrenocortical/terapia , Adulto , Idade de Início , Criança , Pré-Escolar , Intervalo Livre de Doença , Feminino , Humanos , Lactente , Masculino , Metástase Neoplásica , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida
12.
J Am Soc Cytopathol ; 7(2): 99-105, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-31043259

RESUMO

INTRODUCTION: High-risk HPV (HR-HPV) genoprevalence was assessed in cytologic specimens co-tested for HR-HPV in a predominantly Midwestern U.S. population, of which there are limited current data. These baseline data will aid in determining future shifts in HR-HPV genoprevalence. METHODS: A total of 40,739 cervical/endocervical samples collected in PreservCyt (ThinPrep) media at Mayo Clinic, Rochester, MN, underwent HR-HPV co-testing between January 2014 and December 2016 in women aged 30-98 years. This included 37,656 negative for intraepithelial lesion (NIL), 1696 atypical squamous cells of undetermined significance (ASC-US), 159 atypical squamous cells, cannot exclude HSIL (ASC-H), 911 low-grade squamous intraepithelial lesion (LSIL), 188 high-grade intraepithelial lesion (HSIL), and 129 atypical glandular cells of undetermined significance (AGUS) cases. Roche cobas 4800 classified HR-HPV genotypes as 16, 18, or "other" (31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, 68). RESULTS: Of 40,739 co-tested specimens, 3786 were positive for at least one HR-HPV strain. "Other" only genotypes were most prevalent (74.3% of all HR-HPV cases). HPV16 and/or HPV18 were more common in the more significant diagnoses and were present in 59.1% of HSIL. HPV16-only was second most prevalent, with highest prevalence in HSIL (33.3%) and ASC-H (20.6%). HPV16 combined with "other" was third most prevalent, except in AGUS. HR-HPV (all genotypes) was most prevalent in those aged 30-39 years, decreasing with age (P < 0.0001). There was a trend toward HPV16 prevalence increasing with age (P = 0.4244). CONCLUSIONS: HR-HPV "other" combination was most prevalent in all diagnoses except HSIL, in which HPV16 and/or HPV18 (exclusive of "other" genotypes) were most prevalent.

13.
Annu Rev Entomol ; 63: 575-598, 2018 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-29068707

RESUMO

Body size is a key life-history trait influencing all aspects of an organism's biology. Ants provide an interesting model for examining body-size variation because of the high degree of worker polymorphism seen in many taxa. We review worker-size variation in ants from the perspective of factors internal and external to the colony that may influence body-size distributions. We also discuss proximate and ultimate causes of size variation and how variation in worker size can promote worker efficiency and colony fitness. Our review focuses on two questions: What is our current understanding of factors influencing worker-size variation? And how does variation in body size benefit the colony? We conclude with recommendations for future work aimed at addressing current limitations and ask, How can we better understand the contribution of worker body-size variation to colony success? And, what research is needed to address gaps in our knowledge?


Assuntos
Formigas , Variação Biológica da População , Tamanho Corporal , Animais , Evolução Biológica , Interação Gene-Ambiente , Traços de História de Vida
14.
J Clin Endocrinol Metab ; 102(12): 4506-4514, 2017 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-29029287

RESUMO

Context: Historical outcomes in anaplastic thyroid cancer (ATC) have been dismal. Objective: To determine whether an initial intensive multimodal therapy (MMT) is associated with improved ATC survival. Design: MMT was offered to all patients with newly diagnosed ATC treated at the Mayo Clinic from 2003 through 2015; MMT vs care with palliative intent (PI) was individualized considering clinical status and patient preferences. Outcomes were retrospectively analyzed by American Joint Committee on Cancer stage and treatments compared with patient cohort data from 1949 through 1999. Patients: Forty-eight patients (60% male; median age, 62 years); 18 treated with PI, 30 with MMT. Main Outcome Measure: Overall survival (OS) and progression-free survival determined by Kaplan-Meier method. Results: Median OS and 1-year survival for the later cohort were 9 months [95% confidence interval (CI), 4 to 22 months] and 42% (95% CI, 28% to 56%) vs 3 months and 10% for the earlier cohort. Median OS was 21 months compared with 3.9 months in the pooled MMT vs PI groups for the later cohort [hazard ratio (HR), 0.32; P = 0.0006]. Among only patients in the later cohort who had stage IVB disease, median OS was 22.4 vs 4 months (HR, 0.12; 95% CI, 0.03 to 0.44; P = 0.0001), with 68% vs 0% alive at 1 year (MMT vs PI). Among patients with stage IVC cancer, OS did not differ by therapy. Conclusion: MMT appears to convey longer survival in ATC among patients with stage IVA/B disease.


Assuntos
Carcinoma/terapia , Neoplasias da Glândula Tireoide/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma/tratamento farmacológico , Carcinoma/radioterapia , Quimiorradioterapia , Estudos de Coortes , Terapia Combinada , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Cuidados Paliativos , Estudos Retrospectivos , Análise de Sobrevida , Neoplasias da Glândula Tireoide/tratamento farmacológico , Neoplasias da Glândula Tireoide/radioterapia , Tireoidectomia , Resultado do Tratamento
15.
Histopathology ; 69(6): 930-936, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27454570

RESUMO

AIMS: Biphenotypic sinonasal sarcoma (SNS) is a locally aggressive tumour that occurs in the sinonasal region. PAX3-MAML3 has recently been identified as a recurrent fusion gene event in this entity; however, a subset of tumours harbour alternative PAX3 rearrangement without the involvement of MAML3. In this study we sought to characterize the molecular profile of a large series of cases, with a special emphasis on tumours with alternative fusions. METHODS AND RESULTS: Forty-four examples of SNS were screened by fluorescence in-situ hybridization and reverse transcription polymerase chain reaction to better characterize its molecular profile and identify potential novel fusion genes. Twenty-four were positive for PAX3-MAML3 (55%), 15 showed rearrangements of PAX3 without MAML3 involvement (34%), one showed rearrangement of MAML3 without PAX3 involvement, and four were negative for the involvement of either gene (9%). Among 15 cases with PAX3 involvement only, three were found to harbour PAX3-FOXO1. Two of these cases arose in the nasal cavities of female patients (aged 31 and 47 years), and one showed bilateral involvement of the nasal cavities of a 35-year-old male. A fourth case involved the skull base of a 47-year-old male, and was positive for PAX3-NCOA1. Patients with fusion-negative tumours were slightly older. CONCLUSION: More than half of the SNSs in this series were positive for PAX3-MAML3. However, a subset of tumours may harbour alternative PAX3 fusion genes or show no involvement of PAX3. Except for a possible weak association between age and molecular profile, the overall morphological and immunophenotypic features of all cases seem to be similar. Because of the rarity of these tumours, the impact of the molecular profile on the clinical course of these tumours remains to be determined.


Assuntos
Neoplasias dos Seios Paranasais/genética , Sarcoma/genética , Adulto , Biomarcadores Tumorais/genética , Proteínas de Ligação a DNA/genética , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Masculino , Pessoa de Meia-Idade , Proteínas Nucleares/genética , Coativador 1 de Receptor Nuclear/genética , Proteínas de Fusão Oncogênica/genética , Fatores de Transcrição Box Pareados/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores de Transcrição/genética
16.
Endocr Pathol ; 27(3): 243-52, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27262318

RESUMO

Paragangliomas of the urinary bladder can arise sporadically or as a part of hereditary syndromes including those with underlying mutations in the succinate dehydrogenase (SDH) genes, which serve as tumor suppressors. SDH deficiency can be screened for by absence of immunohistochemical detection of SDHB. In this study of 11 cases, clinical follow-up was available for 9/11 cases. The cases were reviewed and graded based on the grading system for adrenal pheochromocytomas and paragangliomas (GAPP) criteria. Immunohistochemistry was performed for Ki67 and SDHB. Proliferative index was calculated by quantification of Ki67-positive cells at hot spots. The medical record was accessed for documentation of germline SDH mutations. Urinary bladder paragangliomas had a female predilection (8/11 cases), and 5/11 cases exhibited metastatic behavior. Patients with metastatic disease tended to be younger (mean age 43 vs 49 years), have larger lesions (5.8 vs 1.5 cm), and presented with catecholamine excess (4/4 vs 2/6 patients with non-metastatic lesions). Patients with metastatic disease had a higher mean Ki67 proliferation rate (4.9 vs 1.3 %) and GAPP score (mean of 5.8 vs 3.8) (p = 0.01). IHC for SDHB expression revealed loss of expression in 2/6 cases of non-metastatic paragangliomas compared to 4/5 patients with metastatic paragangliomas. Interestingly, of these four patients, two had a documented mutation of SDHB, one patient had a SDHC mutation, and another patient had a history of familial disease without mutation analysis being performed. Our study, suggests that SDH loss was suggestive of metastatic behavior in addition to younger age at diagnosis, larger tumor size, and higher Ki67 proliferation rate and catecholamine type.


Assuntos
Paraganglioma Extrassuprarrenal/enzimologia , Paraganglioma Extrassuprarrenal/patologia , Succinato Desidrogenase/biossíntese , Neoplasias da Bexiga Urinária/enzimologia , Neoplasias da Bexiga Urinária/patologia , Adulto , Idoso , Biomarcadores Tumorais/análise , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Succinato Desidrogenase/análise
17.
Oral Surg Oral Med Oral Pathol Oral Radiol ; 121(5): 542-549.e1, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-27017401

RESUMO

OBJECTIVE: Acinic cell carcinoma (AcCC) is an uncommon salivary gland malignancy. We aim to characterize the clinical and pathologic characteristics of AcCC with and without high-grade transformation (HGT). Importantly, cases of mammary analogue secretory carcinoma, a recently described histologic mimic of AcCC, have been excluded by using cytogenetics and molecular studies. STUDY DESIGN: Archival surgical pathology material was obtained for patients diagnosed with AcCC at Mayo Clinic Rochester between 1990 and 2010. Tumors harboring the ETV6-NTRK3 fusion transcript were excluded from analysis by using cytogenetics and molecular studies. Tumors with HGT were characterized by areas with an infiltrative growth pattern, nuclear anaplasia, prominent nucleoli, brisk mitotic activity, geographic necrosis, and stromal desmoplasia. Demographic and clinical data were extracted from the medical records. RESULTS: AcCC with HGT was seen in 8 of 48 cases (17%). Patients with AcCC with HGT were significantly older than patients without HGT (median 69 vs 54 years; P = .04). Angiolymphatic invasion was more common in AcCC with HGT (P = .02). Relapse-free survival and overall survival were significantly worse for cases of AcCC with HGT (hazard ratio 10.4 and 9.3, respectively; P < .0001 for both comparisons). Locoregional recurrence-free survival was not significantly different (P = .12), but distant metastases-free survival was significantly worse in patients with HGT compared with non-HGT patients (P < .0001). CONCLUSIONS: Prognosis for overall survival and distant relapse for AcCC patients with HGT is significantly worse than that for patients without HGT.


Assuntos
Carcinoma de Células Acinares/patologia , Neoplasias das Glândulas Salivares/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Acinares/genética , Carcinoma de Células Acinares/cirurgia , Feminino , Rearranjo Gênico , Humanos , Hibridização in Situ Fluorescente , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Prognóstico , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Neoplasias das Glândulas Salivares/genética , Neoplasias das Glândulas Salivares/cirurgia , Taxa de Sobrevida
18.
Chaos ; 26(1): 013103, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26826855

RESUMO

Measurements of Lagrangian single-point and multiple-point statistics in a quasi-two-dimensional stratified layer system are reported. The system consists of a layer of salt water over an immiscible layer of Fluorinert and is forced electromagnetically so that mean-squared vorticity is injected at a well-defined spatial scale ri. Simultaneous cascades develop in which enstrophy flows predominately to small scales whereas energy cascades, on average, to larger scales. Lagrangian correlations and one- and two-point displacements are measured for random initial conditions and for initial positions within topological centers and saddles. Some of the behavior of these quantities can be understood in terms of the trapping characteristics of long-lived centers, the slow motion near strong saddles, and the rapid fluctuations outside of either centers or saddles. We also present statistics of Lagrangian velocity fluctuations using energy spectra in frequency space and structure functions in real space. We compare with complementary Eulerian velocity statistics. We find that simultaneous inverse energy and enstrophy ranges present in spectra are not directly echoed in real-space moments of velocity difference. Nevertheless, the spectral ranges line up well with features of moment ratios, indicating that although the moments are not exhibiting unambiguous scaling, the behavior of the probability distribution functions is changing over short ranges of length scales. Implications for understanding weakly forced 2D turbulence with simultaneous inverse and direct cascades are discussed.

20.
Endocr Pathol ; 26(4): 291-5, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26304852

RESUMO

Amyloid is a characteristic histologic feature in medullary thyroid carcinomas (MTC). We utilized a novel mass spectrometry-based proteomic analysis to determine if we could identify specific proteins associated with amyloid in MTC. We studied 9 MTC (1 multiple endocrine neoplasia type 2A, 1 familial MTC, and 7 sporadic). Laser microdissection was utilized to sample the amyloid which was then trypsin digested and evaluated by liquid chromatography electrospray tandem MS (LC-MS/MS) which identified the presence of amyloidogenic proteins in all cases of MTC. High levels of calcitonin were identified in all 9 cases of MTC. Secretogranin-1 was identified in 6 of 9 MTC. Calcitonin gene-related peptide was identified in 4 of 9 cases of MTC. LC-MS/MS proteomic analysis provides a rapid, highly specific, and sensitive method for identification of the specific type of amyloid in these endocrine tumors. This approach may allow classification of different forms of endocrine amyloid present in neuroendocrine tumors.


Assuntos
Amiloide/análise , Calcitonina/análise , Carcinoma Neuroendócrino/química , Cromogranina B/análise , Proteômica/métodos , Espectrometria de Massas em Tandem/métodos , Neoplasias da Glândula Tireoide/química , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
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