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1.
Eur Arch Otorhinolaryngol ; 280(7): 3405-3413, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37052687

RESUMO

PURPOSE: The aim of this study is to present incidence, histological subtypes, survival rates, and prognostic factors based on a national cohort of patients with salivary gland carcinoma. METHODS: All Danish patients with submandibular gland carcinoma diagnosed from 1990 to 2015 (n = 206) were included and analyzed following histological re-evaluation. Data were collected by the Danish Head and Neck Cancer Group (DAHANCA). Overall, disease-specific and recurrence-free survival were evaluated. Prognostic factors were analyzed with multivariate Cox Hazard Regression. RESULTS: The study population consisted of 109 (53%) men and 97 (47%) women, median age 62 years (range 11-102). Adenoid cystic carcinoma was the most frequent subtype (50%). Tumour classification T1/T2 (75%) and N0 (78%) was most frequent. The mean crude incidence was 0.17/100,000/year. Most patients (n = 194, 94%) were treated with primary surgery, and 130 (67%) received postoperative radiotherapy. The 5- and 10-year survival rates were for overall survival 64% and 41%, disease-specific survival 74% and 61%, and recurrence-free survival 70% and 56%, respectively. Survival rates were higher for adenoid cystic carcinoma compared to other subtypes, but the difference was not significant in multivariate analysis. Recurrence occurred in 69 patients, and 37 (53.6%) of them had recurrence in a distant site. Advanced T-classification and regional lymph-node metastases had significant negative impact on survival rates. CONCLUSION: The incidence of submandibular gland carcinoma in Denmark was 0.17/100,000/year and stable during the time period. The most frequent subtype was adenoid cystic carcinoma. Half of the recurrences presented in a distant site, and multivariate analysis confirmed that advanced stage was independent negative prognostic factor for recurrence and survival.


Assuntos
Carcinoma Adenoide Cístico , Neoplasias de Cabeça e Pescoço , Neoplasias das Glândulas Salivares , Masculino , Humanos , Feminino , Criança , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Carcinoma Adenoide Cístico/epidemiologia , Carcinoma Adenoide Cístico/terapia , Prognóstico , Glândula Submandibular , Neoplasias das Glândulas Salivares/epidemiologia , Neoplasias das Glândulas Salivares/terapia , Taxa de Sobrevida , Estudos Retrospectivos , Recidiva Local de Neoplasia/epidemiologia
2.
Acta Oncol ; 60(9): 1175-1191, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34319844

RESUMO

BACKGROUND: Human papillomavirus (HPV) is an established prognostic marker in oropharyngeal squamous cell carcinoma. Currently, the role of HPV in sinonasal carcinoma is being explored. OBJECTIVES: This systematic review addresses the role of HPV in sinonasal cancer, establishing the occurrence of HPV-positive cancers and the influence of HPV-positivity on prognosis in sinonasal cancer as well as the utility of the putative surrogate marker of HPV (p16) in sinonasal cancer. MATERIAL AND METHODS: Studies were identified with searches of Medline via PubMed and Embase via OVID (4 May 2020). Articles on original research concerning sinonasal cancer and HPV in humans written in English were included. Case reports with less than five cases were excluded. RESULTS: Initially, 545 articles were identified; 190 duplicate articles were removed leaving 355 articles for title/abstract screening. Title/abstract screening excluded 243 articles, leaving 112 studies assessed for eligibility. After full-text screening, 57 studies were included. All articles investigated the significance of HPV in sinonasal carcinomas. HPV was reported in approximately 30% of sinonasal squamous cell carcinoma (SNSCC), where it was associated with a better prognosis. In sinonasal cancer, p16 is associated with diagnostic pitfalls and a putative utility of p16 in SNSCC has yet to be established. HPV was not frequently reported in other types of sinonasal carcinomas, besides the recently described subtype, HPV-dependent Multiphenotypic Sinonasal Carcinoma. In other types of sinonasal carcinoma, HPV is not frequently found. CONCLUSION: Approximately 30% of SNSCC are HPV-positive. HPV-positivity in SNSCC is associated with improved survival. HPV occurs only rarely in other sinonasal cancers. There is currently not sufficient evidence for p16 as a surrogate marker of HPV in SNSCC.


Assuntos
Alphapapillomavirus , Infecções por Papillomavirus , Neoplasias dos Seios Paranasais , Inibidor p16 de Quinase Dependente de Ciclina , Humanos , Papillomaviridae/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço
3.
Eur Arch Otorhinolaryngol ; 278(4): 1179-1188, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32691231

RESUMO

PURPOSE: Salivary gland carcinoma is a rare disease and studies on epidemiology and outcome require data collection over many years. The aim of this study is to present an update of incidence rates, anatomical sites, histological subtypes, and survival rates based on the Danish national cohort of salivary gland carcinoma patients. METHODS: Data from all Danish patients with salivary gland carcinoma diagnosed from 1990 to 2015 (n = 1601) were included and analyzed following histological reevaluation and reclassification. Overall, disease-specific, and recurrence-free survival were evaluated. Prognostic factors were analyzed with multivariate Cox Hazard Regression. RESULTS: The study population consisted of 769 men and 832 women, median age 62 years (range 6-102). The most frequent anatomic site was the parotid gland (51.8%). Adenoid cystic carcinoma was the most common subtype (24.7%). The majority had tumor classification T1/T2 (65.3%). The mean crude incidence was 1.2/100.000/year with an increase of 1.5% per year. There was no increase in age-adjusted incidence. The 5-, 10-, and 20-year survival rates were for overall survival 68, 52, and 35%, for disease-specific survival, 77, 69, and 64%, and for recurrence-free survival, 75, 64, and 51%, respectively. Age, high-grade histological subtype, advanced T-classification, cervical lymph node metastases, vascular invasion, and involved surgical margins had significantly negative impact on survival rates. CONCLUSION: The age-adjusted incidence has been stable for a period of 26 years. Multivariate analysis confirmed that histological grade, advanced stage, involved surgical margins and vascular invasion are independent negative prognostic factors. Survival rates were stationary compared to earlier reports.


Assuntos
Carcinoma Adenoide Cístico , Neoplasias das Glândulas Salivares , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Adenoide Cístico/epidemiologia , Carcinoma Adenoide Cístico/patologia , Criança , Dinamarca/epidemiologia , Feminino , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Neoplasias das Glândulas Salivares/epidemiologia , Neoplasias das Glândulas Salivares/patologia , Taxa de Sobrevida , Adulto Jovem
4.
Acta Oncol ; 58(11): 1570-1576, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31505992

RESUMO

Objectives: To evaluate changes in incidence and survival of patients diagnosed with hypopharyngeal cancer (HPC) in Denmark in the period 1980-2014.Methods: All patients registered with HPC in the Danish Cancer Registry (DCR) in the period 1980-2014 were included. Age-adjusted incidence rates (AAIRs), average annual percentage change in incidence, and overall survival were calculated.Results: Two thousand and nine patients were included (79.7% men). The overall AAIR increased significantly from 0.3 per 100,000 to 1.1 per 100,000 during the study period, corresponding to an increase of 4.1% per year. The most frequent histology was squamous cell carcinoma (SCC) comprising 90.3%. The overall five-year survival increased with 13.5 percentage points from 13.4% in the period 1980-1985 to 26.9% in the period 2010-2014. Women demonstrated better survival compared to men with a hazard ratio of 0.83, and patients with SCC had better survival compared to the remaining histology groups.Conclusions: This nation-wide study, covering nearly four decades, showed a significant increase in incidence and survival of HPC in Denmark.


Assuntos
Carcinoma de Células Escamosas/epidemiologia , Neoplasias Hipofaríngeas/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Dinamarca/epidemiologia , Feminino , Humanos , Neoplasias Hipofaríngeas/mortalidade , Neoplasias Hipofaríngeas/patologia , Hipofaringe/patologia , Incidência , Masculino , Pessoa de Meia-Idade , Seio Piriforme/patologia , Fatores Sexuais , Análise de Sobrevida , Taxa de Sobrevida , Fatores de Tempo
5.
Acta Oncol ; 58(7): 977-982, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30821560

RESUMO

Background: The purpose of this registry study was to evaluate trends in incidence and survival of laryngeal cancer in the Danish population from 1980 to 2014. Methods: This study includes all patients with laryngeal cancer registered in the Danish Cancer Registry (DCR) in the period 1980-2014. The age-adjusted incidence rate (AAIR) per 100,000 and average annual percent change (AAPC) were calculated. We evaluated the relative survival at five years in relation to gender, anatomical location, year at diagnosis, and histological type. Further, an age-period-cohort (APC) model of incidence was constructed. Results: A total of 8748 patients (82% males) were included. The median age at diagnosis was 60 years, range 18-101 years. The AAIR decreased from 3.6 per 100,000 in 1980 to 2.3 per 100,000 in 2014 with an AAPC of -0.8% (p < .008). Considering the anatomic location, we found that glottic cancer had a significantly better survival at five years compared to the other locations. We observed no significant difference in survival for supraglottic, subglottic and larynx unspecified cancer during the observation period. During the period 1980-2014, we found no improvement in five year relative survival. Conclusions: This nation-wide study reports a significant decrease in the incidence of laryngeal cancer. Glottic cancer had a significantly better survival at five years compared to other locations.


Assuntos
Adenocarcinoma/epidemiologia , Neoplasias Laríngeas/epidemiologia , Tumores Neuroendócrinos/epidemiologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/epidemiologia , Adenocarcinoma/patologia , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Dinamarca/epidemiologia , Feminino , Humanos , Incidência , Neoplasias Laríngeas/patologia , Masculino , Pessoa de Meia-Idade , Tumores Neuroendócrinos/patologia , Sistema de Registros/estatística & dados numéricos , Fatores Sexuais , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Análise de Sobrevida , Taxa de Sobrevida/tendências , Adulto Jovem
6.
Mod Pathol ; 31(8): 1211-1225, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29467480

RESUMO

Adenoid cystic carcinoma is among the most frequent malignancies in the salivary and lacrimal glands and has a grave prognosis characterized by frequent local recurrences, distant metastases, and tumor-related mortality. Conversely, adenoid cystic carcinoma of the breast is a rare type of triple-negative (estrogen and progesterone receptor, HER2) and basal-like carcinoma, which in contrast to other triple-negative and basal-like breast carcinomas has a very favorable prognosis. Irrespective of site, adenoid cystic carcinoma is characterized by gene fusions involving MYB, MYBL1, and NFIB, and the reason for the different clinical outcomes is unknown. In order to identify the molecular mechanisms underlying the discrepancy in clinical outcome, we characterized the phenotypic profiles, pattern of gene rearrangements, and global microRNA expression profiles of 64 salivary gland, 9 lacrimal gland, and 11 breast adenoid cystic carcinomas. All breast and lacrimal gland adenoid cystic carcinomas had triple-negative and basal-like phenotypes, while salivary gland tumors were indeterminate in 13% of cases. Aberrations in MYB and/or NFIB were found in the majority of cases in all three locations, whereas MYBL1 involvement was restricted to tumors in the salivary gland. Global microRNA expression profiling separated salivary and lacrimal gland adenoid cystic carcinoma from their respective normal glands but could not distinguish normal breast adenoid cystic carcinoma from normal breast tissue. Hierarchical clustering separated adenoid cystic carcinomas of salivary gland origin from those of the breast and placed lacrimal gland carcinomas in between these. Functional annotation of the microRNAs differentially expressed between salivary gland and breast adenoid cystic carcinoma showed these as regulating genes involved in metabolism, signal transduction, and genes involved in other cancers. In conclusion, microRNA dysregulation is the first class of molecules separating adenoid cystic carcinoma according to the site of origin. This highlights a novel venue for exploring the biology of adenoid cystic carcinoma.


Assuntos
Carcinoma Adenoide Cístico/genética , Neoplasias Oculares/genética , Doenças do Aparelho Lacrimal/genética , Neoplasias das Glândulas Salivares/genética , Neoplasias de Mama Triplo Negativas/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Adenoide Cístico/patologia , Neoplasias Oculares/patologia , Feminino , Humanos , Doenças do Aparelho Lacrimal/patologia , Masculino , MicroRNAs/análise , Pessoa de Meia-Idade , Neoplasias das Glândulas Salivares/patologia , Neoplasias de Mama Triplo Negativas/patologia , Adulto Jovem
7.
BMC Cancer ; 18(1): 640, 2018 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-29879932

RESUMO

BACKGROUND: The genetic profile for human papilloma virus positive (HPV+) oropharyngeal squamous cell carcinomas (OPSCC) remains largely unknown. The purpose of this study was to sequence tissue material from a large cohort of locoregionally-advanced HPV+ OPSCCs. METHODS: We performed targeted deep sequencing of 395 cancer-associated genes in 114 matched tumor/normal loco-regionally advanced HPV+ OPSCCs. Mutations and copy number aberrations were determined. RESULTS: We identified a total of 3459 mutations with an average of 10 mutations per megabase and a median of 28 variants per sample. The most frequently mutated genes were KALRN (28%), SPTBN1 (32%), KMT2A (31%), ZNRF3 (9%), BNC2 (12%), NOTCH2 (25%), FGFR2 (12%), SMAD2 (6%), and AR (13%). Our findings were dominated by COSMIC signature 5 and 12, represented in other head and neck cancers and in hepatocellular carcinomas, respectively. CONCLUSIONS: We have identified multiple genetic aberrations in HPV+ OPSCCs, and the COSMIC signature 12 as most prevalent. The mutations harbour both therapeutic and prognostic potential.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias Orofaríngeas/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Transcriptoma , Análise Mutacional de DNA , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Neoplasias Orofaríngeas/virologia , Infecções por Papillomavirus/complicações , Carcinoma de Células Escamosas de Cabeça e Pescoço/virologia
8.
Acta Oncol ; 57(9): 1143-1151, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29447088

RESUMO

BACKGROUND: The purpose of the study was to determine trends in age-adjusted incidence rates (AAIR) and survival probability in head and neck cancers (HNCs) in the Danish population from 1980 to 2014. MATERIAL AND METHODS: All patients registered with HNC in the nationwide Danish Cancer Registry from 1980 to 2014 were included. We evaluated the AAIR per 100,000 and the average annual percent change (AAPC). The relative survival probability at 5 years was calculated in relation to gender, anatomical location and histology, and we constructed age-period-cohort models of incidence. RESULTS: About 34,606 patients were included (64.7% men). The AAIR increased from 9.1 per 100,000 in 1980 to 17.4 per 100,000 in 2014 with an AAPC of 2.1%. The greatest incidence increase was observed in oropharyngeal cancer (AAPC: 5.4%) followed by hypopharyngeal cancer (AAPC: 4.2%). Adenocarcinomas had the highest AAPC (5.0%) followed by squamous cell carcinomas (AAPC: 2.0%). The AAPC was significantly higher in women (2.4%) compared with men (1.6%). For all HNC patients, the relative survival at 5 years rose significantly from 49.0% in 1980-1984 to 62.4% in 2010-2014. Women had a significantly higher survival than men with a relative survival of 61.7% compared to 50.0% in men. Laryngeal cancer had the best survival probability of cancers in the upper aerodigestive tract with hypopharyngeal cancer having the poorest survival. CONCLUSION: This nation-wide study showed a significant rise in incidence of HNC for men and women along with a significant increase in relative survival. Oropharyngeal cancer had the highest increase in incidence followed by hypopharyngeal cancer which showed the poorest survival of HNCs.


Assuntos
Neoplasias de Cabeça e Pescoço/epidemiologia , Neoplasias de Cabeça e Pescoço/mortalidade , Dinamarca/epidemiologia , Feminino , Seguimentos , Neoplasias de Cabeça e Pescoço/classificação , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Taxa de Sobrevida/tendências
9.
Acta Oncol ; 57(2): 269-275, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29057724

RESUMO

BACKGROUND: Oropharyngeal carcinomas (OPCs) constitute a significant and increasing proportion of head and neck carcinomas and are an important global cause of morbidity and mortality. The purpose of this study was to determine trends in incidence and survival in OPC in the Danish population from 1980 to 2014. METHODS: This study included all patients registered in the nationwide Danish Cancer Registry over the period 1980-2014. The age-adjusted incidence rates (AAIR) per 100,000, annual percentage change (APC) and average annual percent change (AAPC) were evaluated. Five-year relative survival (RS) was calculated with Cox regression analyses in relation to gender, anatomical location and histology. RESULTS: A total of 6555 patients (69% male) were included, with a median age at diagnosis of 60 years. The AAIR of patients with OPC increased from 0.815 per 100,000 in 1980 to 4.51 per 100,000 in 2014 with an AAPC of 5.3. The 5-year RS increased significantly from 33.1% over the period 1980-1984 to 58.5% (25.4% points) over the period 2010-2014. With no significant difference stratified for gender. Tumors located at the palatine tonsils (n = 3333) and salivary gland OPC (n = 90) had significantly better survival compared with other sub-locations and histology subtypes. In the APC model the birth cohort effect rate ratio increased until 1925 and then decreased until 1935 from which point it increased in the last cohorts. CONCLUSIONS: In this population-based study, we observed a significant increase in the incidence of OPCs and in the RS for OPC. We also identified a profound birth cohort effect on the incidence.


Assuntos
Carcinoma/epidemiologia , Neoplasias Orofaríngeas/epidemiologia , Adulto , Distribuição por Idade , Idoso , Carcinoma/patologia , Dinamarca/epidemiologia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Neoplasias Orofaríngeas/patologia , Modelos de Riscos Proporcionais , Sistema de Registros , Distribuição por Sexo , Taxa de Sobrevida
10.
Acta Oncol ; 57(9): 1152-1158, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29578367

RESUMO

BACKGROUND: Sinonasal cancers are rare and comprise <1% of all malignancies. This study describes incidence and survival in sinonasal carcinomas in Denmark from 1980 to 2014. METHODS: All patients registered in the Danish Cancer Registry in the period were included. Age-adjusted incidence rate, average annual percentage change, and relative survival were calculated. Age-period-cohort models were constructed. RESULTS: 1,720 patients with sinonasal carcinoma (median age 67 years, 63% males) were identified. There was no significant change in age-adjusted incidence; 0.70 in 1980 to 0.43 per 100,000 in 2014 (p > .05). Relative 5- and 10-year survival were 52% and 40% for men, 58% and 42% for women. An increase in 5-year survival from 1980 to 2014 from 46% to 65% (p < .05) was found. Nasal carcinomas had a significantly better relative survival compared to sinus carcinoma, as did squamous cell carcinomas when compared to neuroendocrine malignancies. CONCLUSION: In Denmark between 1980 and 2014, the incidence of sinonasal carcinomas has been stable and the relative survival has increased significantly.


Assuntos
Carcinoma de Células Escamosas/epidemiologia , Carcinoma de Células Escamosas/mortalidade , Neoplasias dos Seios Paranasais/epidemiologia , Neoplasias dos Seios Paranasais/mortalidade , Adolescente , Adulto , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Dinamarca/epidemiologia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Análise de Sobrevida , Taxa de Sobrevida/tendências , Fatores de Tempo , Adulto Jovem
11.
Cereb Cortex ; 27(1): 400-410, 2017 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-26464477

RESUMO

To determine the extent of neocortical involvement in multiple system atrophy (MSA), we used design-based stereological methods to estimate the total numbers of neurons, oligodendrocytes, astrocytes, and microglia in the frontal, parietal, temporal, and occipital cortex of brains from 11 patients with MSA and 11 age- and gender-matched control subjects. The stereological data were supported by cell marker expression analyses in tissue samples from the prefrontal cortex. We found significantly fewer neurons in the frontal and parietal cortex of MSA brains compared with control brains. Significantly more astrocytes and microglia were observed in the frontal, parietal, and temporal cortex of MSA brains, whereas no change in the total number of oligodendrocytes was seen in any of the neocortical regions. There were significantly fewer neurons in the frontal cortex of MSA patients with impaired executive function than in patients with normal executive function. Our results indicate that the involvement of the neocortex in MSA is far more widespread and substantial than previously thought. In addition, our results suggest that the increasingly recognized cognitive impairment in MSA may be related to neuronal loss in the frontal cortex.


Assuntos
Atrofia de Múltiplos Sistemas/patologia , Neocórtex/patologia , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Atrofia de Múltiplos Sistemas/diagnóstico por imagem , Neocórtex/diagnóstico por imagem
12.
J Neurochem ; 136(1): 172-85, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26465922

RESUMO

Together with Parkinson's disease (PD) and dementia with Lewy bodies, multiple system atrophy (MSA) is a member of a diverse group of neurodegenerative disorders termed α-synucleinopathies. Previously, it has been shown that α-synuclein, parkin, and synphilin-1 display disease-specific transcription patterns in frontal cortex in PD, dementia with Lewy bodies, and MSA, and thus may mediate the development of α-synucleinopathies. In this study, the differential expression of α-synuclein isoforms on transcriptional and translational levels was ascertained in MSA patients in comparison with PD cases and normal controls using isoform-specific primers and exon-specific antibodies in substantia nigra, striatum, cerebellar cortex, and nucleus dentatus. These regions are severely affected by α-synuclein pathology and neurodegeneration. Furthermore, we have also investigated transcript levels for parkin and synphilin-1 isoforms. In MSA brains, α-synuclein140 and α-synuclein 112 isoform levels were significantly increased, whereas levels of the α-synuclein 126 isoform were decreased in the substantia nigra, striatum, cerebellar cortex, and nucleus dentatus versus controls. Moreover, in MSA cases, we showed increased levels of parkin isoforms lacking the N-terminal ubiquitin-like domain and an aggregation-prone synphilin-1A isoform that causes neuronal toxicity in MSA. In PD brains, parkin transcript variant 3, 7, and 11 were significantly and specifically over-expressed in the striatum and cerebellar cortex, together with synphilin-1A and 1C. The changes of isoform expression profiles in neurodegenerative diseases suggest alterations in the regulation of transcription and/or splicing events, leading to regional/cellular events that may be important for the highly increased aggregation of α-synuclein in the brain. We report differential expression of α-synuclein, parkin, and synphilin-1 isoforms in multiple system atrophy (MSA) versus Parkinson's disease and normal control brains. We have focused on brain regions that are severely affected by α-synuclein pathology and neurodegeneration in MSA. The reported changes of isoform expression profiles suggest alterations in the regulation of transcription that may be important for aggregation of α-synuclein in the brain.


Assuntos
Encéfalo/metabolismo , Proteínas de Transporte/biossíntese , Atrofia de Múltiplos Sistemas/metabolismo , Proteínas do Tecido Nervoso/biossíntese , Ubiquitina-Proteína Ligases/biossíntese , alfa-Sinucleína/biossíntese , Idoso , Idoso de 80 Anos ou mais , Encéfalo/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Atrofia de Múltiplos Sistemas/patologia , Doença de Parkinson/metabolismo , Doença de Parkinson/patologia , Isoformas de Proteínas/biossíntese
13.
Neurobiol Dis ; 74: 104-13, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25449905

RESUMO

Total numbers of neurons, oligodendrocytes, astrocytes, and microglia in the basal ganglia and red nucleus were estimated in brains from 11 patients with multiple system atrophy (MSA) and 11 age- and gender-matched control subjects with unbiased stereological methods. Compared to the control subjects, the MSA patients had a substantially lower number of neurons in the substantia nigra (p=0.001), putamen (p=0.001), and globus pallidus (p<0.001), and, to a lesser extent in the caudate nucleus (p=0.03). A significantly lower number of oligodendrocytes were only observed in the putamen (p=0.04) and globus pallidus (p=0.01). In the MSA brains the total number of astrocytes was significantly higher in the putamen (p=0.04) and caudate nucleus (p=0.01). In all examined regions a higher number of microglia were found in the MSA brains with the greatest difference observed in the otherwise unaffected red nucleus (p=0.001). The results from the stereological study were supported by cell marker expression analyses showing increased markers for activated microglia. Our results suggest that microgliosis is a consistent and severe neuropathological feature of MSA, whereas no widespread and substantial loss of oligodendrocytes was observed. We have demonstrated significant neuronal loss in the substantia nigra, striatum, and globus pallidus of patients with MSA, while neurons in other basal ganglia nuclei were spared, supporting the region-specific patterns of neuropathological changes in MSA.


Assuntos
Gânglios da Base/patologia , Atrofia de Múltiplos Sistemas/patologia , Núcleo Rubro/patologia , Substância Negra/patologia , Núcleo Subtalâmico/patologia , Idoso , Idoso de 80 Anos ou mais , Astrócitos/metabolismo , Astrócitos/patologia , Gânglios da Base/metabolismo , Contagem de Células , Feminino , Humanos , Masculino , Microglia/metabolismo , Microglia/patologia , Pessoa de Meia-Idade , Atrofia de Múltiplos Sistemas/metabolismo , Neurônios/metabolismo , Neurônios/patologia , Oligodendroglia/metabolismo , Oligodendroglia/patologia , Tamanho do Órgão , Reação em Cadeia da Polimerase em Tempo Real , Núcleo Rubro/metabolismo , Substância Negra/metabolismo , Núcleo Subtalâmico/metabolismo
15.
Cancers (Basel) ; 16(3)2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38339388

RESUMO

Oral squamous cell carcinoma (OSCC) of the tongue is the most common type of oral cavity cancer, and tumor depth of invasion (DOI) is an important prognostic factor. In this study, we investigated the accuracy of intraoral ultrasound and magnetic resonance imaging (MRI) for assessing DOI in patients with OSCC. Histopathological measurement of DOI was used as a reference standard. We conducted a prospective study including patients planned for surgical treatment of OSCC in the tongue. The DOI was measured in an outpatient setting by intraoral ultrasound and MRI, and was compared to the histopathological DOI measurements. Bland-Altman analysis compared the mean difference and 95% limits of agreement (LOA) for ultrasound and MRI, and the Wilcoxon signed-rank test was used to test for significance. The correlation was evaluated using Pearson's correlation coefficient. We included 30 patients: 26 with T1 or T2 tumors, and 4 with T3 tumors. The mean difference from histopathology DOI was significantly lower for ultrasound compared to MRI (0.95 mm [95% LOA -4.15 mm to 6.06 mm] vs. 1.90 mm [95% LOA -9.02 mm and 12.81 mm], p = 0.023). Ultrasound also led to significantly more correct T-stage classifications in 86.7% (26) of patients compared to 56.7% (17) for MRI, p = 0.015. The Pearson correlation between MRI and histopathology was 0.57 (p < 0.001) and the correlation between ultrasound and histopathology was 0.86 (p < 0.001). This prospective study found that intraoral ultrasound is more accurate than MRI in assessing DOI and for the T-staging of oral tongue cancers. Clinical practice and guidelines should implement intraoral ultrasound accordingly.

16.
Diagnostics (Basel) ; 14(6)2024 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-38534997

RESUMO

This study protocol for a prospective, multicenter, diagnostic, clinical trial describes the integration of transoral and transcervical ultrasonography (US) in the initial clinical work-up of patients referred to tertiary head and neck cancer centers with suspected oropharyngeal cancer. The study evaluates the blinded detection rate of oropharyngeal tumors and their US-estimated size and T-stage before histopathology and cross-sectional imaging are available. Magnetic resonance imaging (MRI) scans will be prospectively rated while blinded to T-site histopathology and US. The primary outcome measures of diagnostic accuracy, including sensitivity, specificity, positive and negative predictive values, and overall accuracy, will be reported for both US and MRI. A sub-analysis of prospectively rated 18F-Fluorodeoxyglucose (FDG) positron emission tomography/computerized tomography (PET/CT) scans in patients with clinically suspected unknown primary tumors will also be compared to US and MRI. Secondary outcome measures, including a comparison of tumor size estimation between US, MRI, and CT, will also be reported. This prospective multicenter study will provide clinically impactful information regarding the use of transoral and transcervical US for the diagnostic work-up of oropharyngeal cancer.

17.
Neurochem Res ; 38(6): 1252-9, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23525968

RESUMO

The family of Toll-like receptors (TLRs) plays a key role in controlling innate immune responses to a wide variety of pathogen-associated molecules. It was recently suggested that TLRs have an important role in the crosstalk between neurons and glial cells in the central nervous system, thus their deregulation may play a role in neurodegeneration. Multiple system atrophy (MSA) together with Parkinson's disease belongs to a diverse group of neurodegenerative conditions termed α-synucleinopathies. MSA is a fatal late onset disease characterized by the presence of α-synuclein positive glial cytoplasmic inclusions in oligodendrocytes. α-Synuclein can act as a danger-associated molecular pattern and alter TLR expression thereby activating inflammatory responses in the brain. In this study, using real-time PCR, we assessed the expression of TLRs (TLR1-10) in selected areas of MSA brains (substantia nigra, striatum, cerebral cortex, and nucleus dentatus) in comparison with normal controls. We show evidence for increased levels of mRNA-encoding hTLR-3, hTLR-4, and hTLR-5 in substantia nigra, striatum, cerebral cortex, and nucleus dentatus from MSA brains versus normal controls. The levels of expression of hTLR-1 mRNA were elevated in substantia nigra and striatum whereas levels of hTLR-8 and hTLR-9 mRNAs were significantly higher in cerebella from MSA patients. The concerted alteration of expression of multiple TLRs in MSA brains can be of relevance for understanding the pathogenesis of the disease.


Assuntos
Encéfalo/fisiopatologia , Atrofia de Múltiplos Sistemas/fisiopatologia , Receptores Toll-Like/biossíntese , Idoso , Idoso de 80 Anos ou mais , Encéfalo/patologia , Córtex Cerebelar/metabolismo , Núcleos Cerebelares/metabolismo , Corpo Estriado/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Atrofia de Múltiplos Sistemas/patologia , Neuroglia/metabolismo , Oligodendroglia/metabolismo , Oligodendroglia/patologia , Substância Negra/metabolismo
18.
Cancers (Basel) ; 15(21)2023 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-37958465

RESUMO

Magnetic resonance imaging (MRI) is the preferred imaging modality for oropharyngeal cancers (OPCs), but it has difficulties distinguishing between small OPCs and unilateral tonsil hypertrophy. We hypothesized that surgeon-performed transoral ultrasound (US) could be used to accurately detect T-stage OPCs. We performed a single-center prospective diagnostic accuracy study including patients with suspected or biopsy-verified OPCs during outpatient appointments. All patients were offered transoral US and MRI. If transoral US could not be tolerated by the patient, transcervical US was performed. The primary outcome was the diagnostic accuracy of detecting OPCs with US compared to MRI, using histopathology as the reference standard. The secondary outcome was comparing the primary tumor diameters between US and MRI blinded to each other. Out of the 26 patients included in the study, 21 (81%) had OPCs. Transoral US could be performed in 21/21 and 1/5 patients with suspected palatine and lingual tonsil OPCs, respectively. Overall, US diagnostic accuracy was 92%, compared to 81% with MRI (p = 0.37). US and MRI had a high correlation between tumor diameters in the anteroposterior diameter (R = 0.80, p < 0.001), corresponding to the depth axis on US. In conclusion, this small study showed the promise and feasibility of transoral US to improve the initial clinical evaluations of patients with suspected OPCs.

19.
J Imaging ; 9(9)2023 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-37754938

RESUMO

Surgery is the primary treatment for tongue cancer. The goal is a complete resection of the tumor with an adequate margin of healthy tissue around the tumor.Inadequate margins lead to a high risk of local cancer recurrence and the need for adjuvant therapies. Ex vivo imaging of the resected surgical specimen has been suggested for margin assessment and improved surgical results. Therefore, we have developed a novel three-dimensional (3D) ultrasound imaging technique to improve the assessment of resection margins during surgery. In this research protocol, we describe a study comparing the accuracy of 3D ultrasound, magnetic resonance imaging (MRI), and clinical examination of the surgical specimen to assess the resection margins during cancer surgery. Tumor segmentation and margin measurement will be performed using 3D ultrasound and MRI of the ex vivo specimen. We will determine the accuracy of each method by comparing the margin measurements and the proportion of correctly classified margins (positive, close, and free) obtained by each technique with respect to the gold standard histopathology.

20.
J Imaging ; 8(12)2022 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-36547494

RESUMO

The margin of the removed tumor in cancer surgery has an important influence on survival. Adjuvant treatments, prognostic complications, and financial costs are required when the pathologist observes a close/positive surgical margin. Ex vivo imaging of resected cancer tissue has been suggested for margin assessment, but traditional cross-sectional imaging is not optimal in a surgical setting. Instead, three-dimensional (3D) ultrasound is a portable, high-resolution, and low-cost method to use in the operation room. In this study, we aimed to investigate the accuracy of 3D ultrasound versus computed tomography (CT) to measure the tumor volume in an animal model compared to gross pathology assessment. The specimen was formalin fixated before systematic slicing. A slice-by-slice area measurement was performed to compare the accuracy of the 3D ultrasound and CT techniques. The tumor volume measured by pathological assessment was 980.2 mm3. The measured volume using CT was 890.4 ± 90 mm3, and the volume using 3D ultrasound was 924.2 ± 96 mm3. The correlation coefficient for CT was 0.91 and that for 3D ultrasound was 0.96. Three-dimensional ultrasound is a feasible and accurate modality to measure the tumor volume in an animal model. The accuracy of tumor delineation on CT depends on the soft tissue contrast.

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