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1.
J Am Acad Dermatol ; 89(6): 1177-1184, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37634740

RESUMO

BACKGROUND: The prognosis of patients with atypical fibroxanthoma (AFX) and pleomorphic dermal sarcoma (PDS) remains uncertain and no standardized follow-up programs have been established. OBJECTIVE: To recommend a standardized follow-up program of patients with AFX and PDS based on nationwide long-term estimates of local recurrence and metastasis. METHODS: All patients with AFX and PDS in Denmark between 2002 and 2022 were included. Danish National Registries were used to estimate the risks of local recurrence and metastasis for AFX and PDS. RESULTS: The 5-year risk of local recurrence was 10% for AFX and 17% for PDS. The 5-year risk of metastasis was 0.8% for AFX and 16% for PDS. PDS metastasized within 3 years in >90% of the patients with the lungs as the primary metastasis site (50%). Invasion beyond the subcutis, perineural/intravascular infiltration, and increasing age significantly increased the risk of PDS relapse. LIMITATIONS: Risk of misclassification and lack of detailed surgical information. CONCLUSION: The follow-up of patients with AFX can be limited to clinical visits for 4 years. Patients with PDS should be followed with clinical visits and PET/CT twice a year for the first 3 years and once a year for a minimum of 1 year.


Assuntos
Histiocitoma Fibroso Maligno , Neoplasias Cutâneas , Humanos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Recidiva Local de Neoplasia/epidemiologia , Neoplasias Cutâneas/patologia , Histiocitoma Fibroso Maligno/epidemiologia
2.
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
3.
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
4.
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
5.
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
6.
BMC Cancer ; 17(1): 572, 2017 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-28841839

RESUMO

BACKGROUND: Tumor-specific biomarkers are a prerequisite for the development of targeted imaging and therapy in oral squamous cell carcinoma (OSCC). urokinase-type Plasminogen Activator Receptor (uPAR), Tissue Factor (TF) and Epidermal Growth Factor Receptor (EGFR) are three biomarkers that exhibit enhanced expression in many types of cancers, and have been investigated as potential biomarkers for targeted strategies and prognostication. The aim of the study was to investigate the expression patterns of uPAR, TF and EGFR and their potential prognostic value in OSCC. METHODS: Immunohistochemical expression of uPAR, TF and EGFR in tumor resection specimens from 191 patients with primary OSCC was analyzed. Overall (OS) and disease-free survival (DFS) was calculated. Associations between biomarker expression, clinicopathological factors and patient survival was analyzed using the Cox proportional hazards model for univariate and multivariate analysis, log rank and Kaplan-Meier statistics. RESULTS: uPAR and TF exhibited a highly tumor-specific expression pattern while EGFR also showed expression in normal tissues outside the tumor compartment. The overall positive expression rate of uPAR, TF and EGFR was 95%, 58% and 98%, respectively. High uPAR expression across the entire cohort was negatively associated with OS (p = 0.031, HR = 1.595 (95%CI 1.044-2.439)) in univariate analysis. The 5-year OS for high and low uPAR expression was 39% and 56%, respectively. The expression of TF and EGFR was not associated with survival outcome. CONCLUSIONS: This study may suggest that uPAR and TF could potentially be attractive targets for molecular imaging and therapy in OSCC due to high positive expression rates and tumor-specific expression patterns. High uPAR expression was significantly associated with a reduced survival. uPAR seems to be a prognostic biomarker in oral cancer.


Assuntos
Apoenzimas/genética , Carcinoma de Células Escamosas/terapia , Receptores ErbB/genética , Neoplasias Bucais/terapia , Receptores de Ativador de Plasminogênio Tipo Uroquinase/genética , Tromboplastina/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Apoenzimas/análise , Biomarcadores Tumorais/análise , Carcinoma de Células Escamosas/metabolismo , Intervalo Livre de Doença , Receptores ErbB/análise , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/metabolismo , Modelos de Riscos Proporcionais , Receptores de Ativador de Plasminogênio Tipo Uroquinase/análise , Tromboplastina/análise , Adulto Jovem
7.
Acta Oncol ; 56(9): 1204-1209, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28366106

RESUMO

BACKGROUND: Oral carcinomas (OCs) make up a significant proportion of head and neck carcinomas (HNCs) and are an important cause of morbidity and mortality globally. The purpose of this population-based study was to determine trends in incidence and survival in OC in the Danish population from 1980 to 2014. MATERIAL AND METHODS: This study covered all patients registered in the nationwide Danish cancer registry (DCR) in the period 1980-2014. Age-adjusted incidence rate (AAIR) per 100,000 and annual percentage change (APC) were evaluated. Also, 5-year overall survival (OS) was calculated with Cox regression analysis in relation to location, gender, age, and calendar year at diagnosis. RESULTS: Altogether, 8299 patients with oral cancer were identified, 5062 (61%) of whom were males and 3237 (39%) were females. The median age at diagnosis was 63 years. The AAIR of patients with OC increased from 1.9 per 100,000 in 1980 to 3.5 per 100,000 in 2014, and we observed a significant increase in 5-year OS of 12% points (a relative increase of 38%) from the period 1980-1984 to 2005-2009. Women were found to have a better prognosis than men. CONCLUSIONS: We found an unexpected increase in the age-standardized incidence of OC during the last 30 years in Denmark, and also an improvement in survival. The 5-year OS was significantly better in recent years even when we adjusted the analysis for relevant covariates.


Assuntos
Neoplasias Bucais/epidemiologia , Neoplasias Bucais/mortalidade , Sistema de Registros , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Dinamarca/epidemiologia , Feminino , Humanos , Incidência , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Prognóstico , Taxa de Sobrevida , Fatores de Tempo , Adulto Jovem
8.
Br J Ophthalmol ; 105(6): 878-883, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-31649051

RESUMO

AIMS: Human papillomavirus (HPV) is considered a causative agent for the development of a broad range of human carcinomas. The role of HPV in the development of conjunctival intraepithelial neoplasia (CIN) and carcinoma (cSCC) remains unclear. The purpose of the present study was to investigate the HPV prevalence in a nationwide cohort and to describe clinical and histopathological features in relation to HPV status. METHODS: All cases of CIN and cSCC in Denmark from 1980 to 2016 were included. We combined p16 immunohistochemistry (IHC), RNA in situ hybridisation (RNA ISH) and HPV DNA PCR to detect HPV. The results were correlated to clinical and histopathological parameters. RESULTS: One hundred twelve primary tumours and 33 recurrent tumours were included for HPV analysis. Twenty-four (21%) of the primary tumours were HPV positive by PCR. Eighteen of out 19 HPV-positive tumours were positive by RNA ISH. HPV16 was the most prevalent genotype (n=18, 75%). The patients with HPV-positive tumours were significantly younger (mean difference 11.5 years, 95% CI 5.2 to 17.9, p=0.0005) and had a higher recurrence compared with patients with HPV-negative tumours (HR 2.30, 95% CI 1.02 to 5.21, p=0.046). The HPV-positive tumours were associated with a positive p16 IHC and a non-keratinising morphology. CONCLUSION: We describe distinct clinical and histopathological features associated with HPV status in cSCC. The finding of transcriptionally active HPV in this material lends support to a causal role of HPV in a subset of cSCC.


Assuntos
Carcinoma de Células Escamosas/diagnóstico , Túnica Conjuntiva/patologia , Neoplasias da Túnica Conjuntiva/diagnóstico , DNA Viral/análise , Papillomaviridae/genética , Infecções por Papillomavirus/diagnóstico , Idoso , Carcinoma de Células Escamosas/virologia , Túnica Conjuntiva/virologia , Neoplasias da Túnica Conjuntiva/virologia , Feminino , Seguimentos , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Infecções por Papillomavirus/virologia , Estudos Retrospectivos
9.
Ugeskr Laeger ; 180(51)2018 Dec 17.
Artigo em Dinamarquês | MEDLINE | ID: mdl-30618362

RESUMO

Danish national guidelines recommend discontinuation of metformin 48 h prior to general anaesthesia due to the presumed increased risk of lactic acidosis. By reviewing recent studies concerning the risk of metformin-associated lactic acidosis it is found, that studies indicate, that metformin does not increase the risk of lactic acidosis. However, comorbidities such as cardiovascular insufficiency, sepsis, dehydration and impaired kidney function are risk factors. New guidelines propose discontinuation of metformin on the day of surgery. Patients with Type 2 diabetes and comorbidities should have the levels of arterial pH and lactate monitored.


Assuntos
Acidose Láctica/prevenção & controle , Anestesia Geral , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/efeitos adversos , Metformina/efeitos adversos , Acidose Láctica/induzido quimicamente , Acidose Láctica/etiologia , Anestesia Geral/efeitos adversos , Comorbidade , Humanos , Hipoglicemiantes/administração & dosagem , Metformina/administração & dosagem , Cuidados Pré-Operatórios , Fatores de Risco
10.
Oral Oncol ; 83: 46-52, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-30098778

RESUMO

BACKGROUND: MicroRNAs (miRNAs) hold promise as diagnostic cancer biomarkers. Here we aimed to define the miRNome in oral squamous cell carcinoma (OSCC) and normal oral mucosa (NOM), and to identify and validate new diagnostic miRNAs and miRNA combinations in formalin-fixed paraffin-embedded (FFPE) tissue samples and plasma samples. METHODS: We performed next-generation miRNA sequencing in FFPE tissue samples of OSCC (n = 80) and NOM (n = 8). Our findings were validated by quantitative polymerase chain reaction (qPCR) analysis of OSCC (n = 195) and NOM (n = 103) FFPE tissue samples, and plasma samples from OSCC patients (n = 55) and healthy persons (n = 18). RESULTS: The OSCC miRNome included 567 miRNAs, 66 of which were differentially expressed between OSCC and NOM. Using qPCR data, we constructed receiver operating curves to classify patients as NOM or OSCC based on miRNA combinations. The area under the curve was of 0.92 from FFPE tissue (miR-204-5p, miR-370, miR-1307, miR-193b-3p, and miR-144-5p), and 1.0 from plasma samples (miR-30a-5p and miR-769-5p). Model calibration and discrimination were evaluated using 10-fold cross-validation. CONCLUSIONS: Analysis of the miRNome from many OSCC cases improves our knowledge of the importance of individual miRNAs and their predictive potential in OSCC. We successfully identified miRNA classifiers in FFPE OSCC tissue and plasma with a high discriminatory ability between OSCC and NOM. The proposed combination of miR-30a-5p and miR-769-5p in plasma from OSCC patients could serve as a minimal invasive biomarker for diagnosis and control of T-site recurrences.


Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas/diagnóstico , MicroRNAs/metabolismo , Neoplasias Bucais/diagnóstico , Biomarcadores Tumorais/sangue , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Feminino , Humanos , Masculino , MicroRNAs/sangue , Pessoa de Meia-Idade , Mucosa Bucal/metabolismo , Neoplasias Bucais/genética , Neoplasias Bucais/metabolismo
11.
Thyroid ; 28(9): 1128-1133, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29943676

RESUMO

BACKGROUND: Thyroid cancer constitutes a major and increasing proportion of head and neck cancers in children and adolescents. The purpose of this study was to determine the incidence and survival of thyroid cancer in Danish patients aged 0-24 years from 1980 to 2014. METHODS: Patients aged 0-24 years registered with primary thyroid cancer in the Danish Cancer Registry or the Danish Pathology Data Bank during 1980-2014 were included. Crude incidence rates and age-adjusted incidence rates (AAIR) per 100,000, average annual percent change (AAPC), and overall survival (OS) were evaluated in relation to sex, histopathological tumor type, age at diagnosis, and year of diagnosis. RESULTS: A total of 297 thyroid cancer patients (72% female, 72% papillary carcinoma) were identified. The AAIR per 100,000 increased significantly from 0.36 in 1980 to 0.97 in 2014, with an AAPC of 2.9%. There was no significant increase in incidence among children and adolescents (0-17 years). However, among young adults (18-24 years), a significant increase in incidence was observed (AAPC 3.7%). The incidence of thyroid cancer increased with age from 0.05 among infants aged 0 years to 1.73 among young adults aged 24 years. Female patients and papillary carcinoma showed significant increase in incidence (AAPC 3.3% and 3.2%), whereas male patients and other histopathological tumor types showed no change. The 15-year OS was 99%. The lowest 15-year OS was observed among patients with medullary carcinomas at 96%. There was no significant difference in OS between groups based on histopathological tumor type, and there was no significant change in OS over time. CONCLUSION: In this nationwide study, no change in OS was observed, but a significant increase was seen in the incidence of thyroid cancer among young adults (aged 18-24 years), mainly attributed to an increase among females and patients with papillary carcinoma. No increase in incidence was seen among children and adolescents. These findings demonstrate the excellent prognosis for children and adolescents diagnosed with thyroid cancer.


Assuntos
Adenocarcinoma Folicular/epidemiologia , Câncer Papilífero da Tireoide/epidemiologia , Neoplasias da Glândula Tireoide/epidemiologia , Adenocarcinoma Folicular/mortalidade , Adolescente , Criança , Pré-Escolar , Dinamarca/epidemiologia , Feminino , Humanos , Incidência , Lactente , Masculino , Sistema de Registros , Taxa de Sobrevida , Câncer Papilífero da Tireoide/mortalidade , Neoplasias da Glândula Tireoide/mortalidade , Adulto Jovem
12.
Cancer Epidemiol ; 55: 81-87, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29852396

RESUMO

BACKGROUND: Thyroid cancer incidence has been reported to be increasing since the 1970 s. The aim of this study was to investigate the change in incidence and survival from 1980 to 2014 in Denmark. METHODS: We identified patients registered with thyroid cancer in the period 1980-2014. We evaluated the age-adjusted incidence rate (AAIR) and the average annual percentage change (AAPC), constructed age-period-cohort models (APCs), and evaluated relative survival (RS). RESULTS: We included 5139 patients. The AAIR was 1.6 cases per 100,000 in 1980 and 4.5 cases in 2014 with an AAPC of 3.4%. The AAIR for papillary carcinomas (n = 2864) quintupled in the study period, and accounts for most of the observed increase in incidence with an AAPC of 4.9%. Follicular carcinomas (n = 920) nearly tripled in AAIR and had the second greatest increase in AAPC. Papillary carcinomas had the best prognosis with 1-year and 5-year RSs of 95% and 91%, followed by the follicular carcinomas with 1-year and 5-year RSs of 90% and 80%, respectively. Anaplastic carcinomas (n = 320) had the worst prognosis with 1-year and 5-year RSs of 18% and 12%. We found a significant age effect in the APC model for the incidence of thyroid cancer but no significant cohort or period effects. CONCLUSION: The incidence of thyroid cancer is rising. This is primarily attributable to an increase in papillary carcinomas. The relative survival has improved significantly in Denmark since 1980. The cause of the increasing incidence remains to be established, but enhanced diagnostic scrutiny and increased iodine intake may be influential.


Assuntos
Mortalidade/tendências , Sistema de Registros/estatística & dados numéricos , Neoplasias da Glândula Tireoide/epidemiologia , Neoplasias da Glândula Tireoide/mortalidade , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Carcinoma/epidemiologia , Carcinoma/mortalidade , Carcinoma Papilar/epidemiologia , Carcinoma Papilar/mortalidade , Criança , Pré-Escolar , Dinamarca/epidemiologia , Feminino , Humanos , Incidência , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Fatores de Tempo , Adulto Jovem
13.
Oncotarget ; 8(11): 18227-18237, 2017 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-28212555

RESUMO

It is challenging to identify at diagnosis those patients with early oral squamous cell carcinoma (OSCC), who have a poor prognosis and those that have a high risk of harboring occult lymph node metastases. The aim of this study was to develop a standardized and objective digital scoring method to evaluate the predictive value of tumor budding. We developed a semi-automated image-analysis algorithm, Digital Tumor Bud Count (DTBC), to evaluate tumor budding. The algorithm was tested in 222 consecutive patients with early-stage OSCC and major endpoints were overall (OS) and progression free survival (PFS). We subsequently constructed and cross-validated a binary logistic regression model and evaluated its clinical utility by decision curve analysis. A high DTBC was an independent predictor of both poor OS and PFS in a multivariate Cox regression model. The logistic regression model was able to identify patients with occult lymph node metastases with an area under the curve (AUC) of 0.83 (95% CI: 0.78-0.89, P <0.001) and a 10-fold cross-validated AUC of 0.79. Compared to other known histopathological risk factors, the DTBC had a higher diagnostic accuracy. The proposed, novel risk model could be used as a guide to identify patients who would benefit from an up-front neck dissection.


Assuntos
Carcinoma de Células Escamosas/diagnóstico por imagem , Linfonodos/diagnóstico por imagem , Neoplasias Bucais/diagnóstico por imagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/patologia , Feminino , Humanos , Linfonodos/patologia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/patologia , Estadiamento de Neoplasias , Prognóstico
14.
Oral Oncol ; 74: 105-110, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-29103737

RESUMO

INTRODUCTION: The incidence of oropharyngeal squamous cell carcinoma (OPSCC) is increasing, but data on the incidence of synchronous, bilateral tonsillar squamous cell carcinomas (BiTSCCs) is sparse. In this study, we report the incidence and tumour characteristics of BiTSCCs in a population-based, consecutive cohort of OPSCCs. METHODS: We identified all patients diagnosed with tonsillar squamous cell carcinoma (TSCC) in eastern Denmark during a 15-year period to detect the incidence of synchronous BiTSCCs. The tumours were assessed for p16Ink4a expression, the presence of HPV DNA and HPV genotypes. Furthermore, we systematically reviewed the literature examining BiTSCCs. RESULTS: Of the total of 1119 TSCCs diagnosed in eastern Denmark from 2000 to 2014, we identified 12 BiTSCCs, nine of which initially presented as a cancer of unknown primary (CUP) in the neck. Nine cases were bilaterally HPV16 positive (HPV16+), while two cases were HPV16+ in one tonsil and respectively, HPV33 and HPV35 positive in the contralateral tonsil. One case was bilaterally HPV-negative. We also identified an increase in the incidence of BiTSCCs after 2012 when histological examination of the entire tonsil tissue became routine, suggesting that BiTSCCs might be underdiagnosed. In the literature, we identified 15 studies from six countries, encompassing 25 cases in total. CONCLUSIONS: BiTSCCs were primarily HPV16+ and were most often diagnosed as part of the diagnostic work-up for CUP. We found an incidence of 9% BiTSCCs in patients with TSCC after 2012 and we therefore recommend focusing on putative BiTSCC with total embedding and histological examination of tonsils harvested by bilateral tonsillectomies.


Assuntos
Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/virologia , Genótipo , Papillomaviridae/genética , Neoplasias Tonsilares/patologia , Adulto , Idoso , Feminino , Genes Virais , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Tonsilares/virologia
15.
Eur J Cancer ; 70: 75-82, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27888679

RESUMO

BACKGROUND: Human papillomavirus (HPV) is a critical element in the rising incidence of oropharyngeal squamous cell carcinoma (OPSCC), although whether this trend will continue, and the types of HPV responsible, are currently unknown. We previously demonstrated an increased incidence of HPV-related OPSCC in the high HPV prevalence area of Eastern Denmark from 2000 to 2010. Therefore, we investigated if the incidence for OPSCC continued to rise, the association to HPV and putative HPV-types in Eastern Denmark from 2011 to 14. We then projected the expected incidence of OPSCC versus cervical cancer through to 2020. PATIENTS AND METHODS: Patients with OPSCC (tonsillar squamous cell carcinoma [TSCC] and base of tongue squamous cell carcinoma [BSCC]) were identified via the Danish Head and Neck Cancer Group and the Danish Pathology Databank (n = 700). Tumours were re-reviewed and assessed using p16 immunohistochemistry, HPV DNA polymerase chain reaction (PCR), with genotyping by next generation sequencing. RESULTS: Sixty-two percent (432/700) of tumours were HPV-positive (HPV+). The total incidence rate (per 100.000) for OPSCC increased from 4.0 in 2011 to 4.5 in 2014, primarily due to a rise in HPV+ TSCCs and HPV+ BSCCs, although numbers of HPV-negative (HPV-) OPSCC also increased during the study period. The majority of HPV+ tumours were HPV16 DNA positive (86%), but we also identified HPV33 DNA (6%), HPV35 DNA (4%) and others (3%), including HPV18, 26, 31, 45, 56, 58, 59 and HPV67. CONCLUSION: An increasing incidence of OPSCC is driven primarily by HPV+ OPSCC. Sixty-two percent of tumours were HPV+, which is a high-prevalence, although the lower number of HPV- cases has yet to stabilise. HPV16 was the predominant genotype, although a significant proportion (14%) was of another genotype. Our projections suggest that the number of HPV+ OPSCC will exceed that of cervical cancer in 2016 in Eastern Denmark.


Assuntos
Carcinoma de Células Escamosas/epidemiologia , Neoplasias Orofaríngeas/epidemiologia , Adulto , Idoso , Carcinoma de Células Escamosas/virologia , Dinamarca/epidemiologia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Neoplasias Orofaríngeas/virologia , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/epidemiologia , Prevalência
16.
Head Neck ; 38 Suppl 1: E1033-40, 2016 04.
Artigo em Inglês | MEDLINE | ID: mdl-26040238

RESUMO

BACKGROUND: The purpose of this study was to examine the diagnostic accuracy of detecting lymph node metastases and to identify predictive and prognostic clinicopathological factors in patients with oral squamous cell carcinoma (OSCC) undergoing sentinel lymph node biopsy (SLNB). METHODS: All patients diagnosed with cT1 to T2N0 OSCC who underwent a diagnostic SLNB between 2007 and 2013 were included. RESULTS: We identified 253 patients, of whom 27% had a positive sentinel lymph node (SLB). The false-negative rate, sensitivity, and negative predictive value (NPV) were 5%, 88%, and 95%, respectively. Patients with micrometastases as well as macrometastases had a separately, significantly shorter disease-specific survival than patients with pN0 disease. In a logistic regression model, the maximum tumor thickness, perineural invasion, and differentiation grade were independent predictive factors for the presence of metastases. CONCLUSION: These data support the use of the SLNB technique as an accurate and safe staging tool in patients with OSCC with a cN0 neck. © 2015 Wiley Periodicals, Inc. Head Neck 38: E1033-E1040, 2016.


Assuntos
Metástase Linfática/diagnóstico , Neoplasias Bucais/patologia , Biópsia de Linfonodo Sentinela , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/diagnóstico , Estadiamento de Neoplasias , Estudos Retrospectivos , Sensibilidade e Especificidade
17.
PLoS One ; 9(11): e110456, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25369118

RESUMO

BACKGROUND: The purpose of this study was to examine the prevalence of human papillomavirus (HPV) in patients with head and neck squamous cell carcinoma of unknown primary (CUP). METHODS: All patients diagnosed with and treated for CUP between January 1, 2000, and June 1, 2011, at two Danish medical centers were included. All patients received a thorough diagnostic work-up, including FDG-PET, before being diagnosed as CUP. We determined the HPV status in all patients using a combination of HPV DNA PCR and p16 stain. In addition, clinical information on the study patients was retrieved from clinical records. RESULTS: Of the identified 60 patients with CUP, 13 were shown to be positive for HPV DNA, amounting to 22% of the study population. In addition, we were able to show a clear disease-free and overall-survival benefit in the HPV-positive group, with a hazard ratio of 0.16 (95% CI: 0.038-0.67) for over-all survival. This survival benefit was also apparent when adjusted for advanced age in a multivariate Cox regression analysis. CONCLUSION: A fairly large percentage of CUP cases are HPV-related, and because this is related to both the location and prognosis, we recommend HPV testing as part of the diagnostic work-up.


Assuntos
Carcinoma de Células Escamosas/diagnóstico , Neoplasias de Cabeça e Pescoço/diagnóstico , Papillomavirus Humano 16/isolamento & purificação , Idoso , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , DNA Viral/análise , Intervalo Livre de Doença , Feminino , Neoplasias de Cabeça e Pescoço/mortalidade , Neoplasias de Cabeça e Pescoço/patologia , Papillomavirus Humano 16/genética , Humanos , Estimativa de Kaplan-Meier , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Neoplasias Primárias Desconhecidas , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/virologia , Reação em Cadeia da Polimerase , Prevalência , Prognóstico , Modelos de Riscos Proporcionais
18.
Oral Surg Oral Med Oral Pathol Oral Radiol ; 117(3): 335-342.e1, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24528792

RESUMO

The most severe forms of xerostomia and salivary gland dysfunction, as well as a severely reduced quality of life, are seen in Sjögren syndrome (SS) and after radiotherapy for head and neck cancer. For both conditions, no effective regenerative therapies yet exist. Thus, the aim of this article was to assess, through systematic review, the potential benefit of mesenchymal stem cell (MSC) therapy in radiation-induced and SS-related salivary gland dysfunction and xerostomia. We searched PubMed/MEDLINE, Embase, Web of Science, the Cochrane Database of Systematic Reviews, the World Health Organization Clinical Trials Registry Platform, and Google Scholar. We identified 6 separate study comparisons eligible for inclusion. Owing to the limited number of studies, we conclude that more randomized, adequately powered clinical trials are needed to validate the potential beneficial effect of MSCs on salivary gland dysfunction and xerostomia. Nonetheless, the preliminary studies identified in the present review were encouraging for further research.


Assuntos
Neoplasias de Cabeça e Pescoço/radioterapia , Transplante de Células-Tronco Mesenquimais , Doenças das Glândulas Salivares/terapia , Xerostomia/terapia , Animais , Humanos , Doenças das Glândulas Salivares/etiologia , Xerostomia/etiologia
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