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1.
Head Neck ; 38(5): 775-81, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-25521093

RESUMO

BACKGROUND: Alternative splicing of the vascular endothelial growth factor (VEGF) gene results in a family of antiangiogenic isoforms (VEGFxxx b), not yet investigated in squamous cell carcinoma of the head and neck (SCCHN). We examined, therefore, the prognostic value of the relative expression of VEGF isoforms in SCCHN. METHODS: A tissue microarray comprising 187 SCCHNs was studied by immunohistochemistry with total VEGF (panVEGF) and VEGFxxx b-specific antibodies, and scored by 2 assessors for intensity and proportion. Scores were combined and expression ratios calculated. RESULTS: No meaningful significant differences were observed between panVEGF, VEGFxxx b, or expression ratio, and presence of lymphatic metastasis, or overall survival. This held true when tumor subsites were analyzed independently and when human papillomavirus (HPV) was accounted for in the oropharyngeal subgroup. CONCLUSION: Differential VEGF isoform expression is not a reliable prognostic biomarker for either the clinically node negative/pathologically node-positive neck or overall survival in pharyngeal and laryngeal SCCHNs.


Assuntos
Carcinoma de Células Escamosas/metabolismo , Neoplasias de Cabeça e Pescoço/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Processamento Alternativo , Humanos , Imuno-Histoquímica , Metástase Linfática , Pessoa de Meia-Idade , Prognóstico , Isoformas de Proteínas/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço , Taxa de Sobrevida , Análise Serial de Tecidos
2.
Carcinogenesis ; 36(6): 648-55, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25896444

RESUMO

Head and neck squamous cell carcinomas (HNSCC) are treated with surgery, radiotherapy and cisplatin-based chemotherapy, but survival from locally-advanced disease remains poor, particularly in patients whose tumors are negative for Human papillomavirus (HPV). Type 1 IGF receptor (IGF-1R) is known to promote tumorigenesis and resistance to cancer therapeutics. Here, we assessed IGF-1R immunohistochemistry on tissue microarrays containing 852 cores from 346 HNSCC patients with primary tumors in the oropharynx (n = 231), larynx (85), hypopharynx (28), oral cavity (2). Of these, 236 (68%) were HPV-negative, 110 (32%) positive. IGF-1R was detected in the cell membrane of 36% and cytoplasm of 92% of HNSCCs; in 64 cases with matched normal tonsillar epithelium, IGF-1R was overexpressed in the HNSCCs (P < 0.001). Overall survival (OS) and disease-specific survival (DSS) were reduced in patients whose tumors contained high membrane IGF-1R [OS: hazard ratio (HR) = 1.63, P = 0.006; DSS: HR = 1.63, P = 0.016], cytoplasmic IGF-1R (OS: HR = 1.58, P = 0.009; DSS: HR = 1.58, P = 0.024) and total IGF-1R (OS: HR = 2.02, P < 0.001; DSS: HR = 2.2, P < 0.001). High tumor IGF-1R showed significant association with high-tumor T-stage (P < 0.001) and HPV-negativity (P < 0.001), and was associated with shorter OS when considering patients with HPV-positive (P = 0.01) and negative (P = 0.006) tumors separately. IGF-1R was independently associated with survival in multivariate analysis including HPV, but not when lymphovascular invasion, perineural spread and T-stage were included. Of these factors, only IGF-1R can be manipulated; the association of IGF-1R with aggressive disease supports experimental incorporation of anti-IGF-1R agents into multimodality treatment programs for HPV-negative and high IGF-1R HPV-positive HNSCC.


Assuntos
Carcinoma de Células Escamosas/mortalidade , Neoplasias de Cabeça e Pescoço/mortalidade , Infecções por Papillomavirus/complicações , Receptor IGF Tipo 1/biossíntese , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/virologia , Transformação Celular Neoplásica/genética , Terapia Combinada , Intervalo Livre de Doença , Resistencia a Medicamentos Antineoplásicos/genética , Feminino , Neoplasias de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Papillomaviridae , Carcinoma de Células Escamosas de Cabeça e Pescoço , Adulto Jovem
3.
Laryngoscope ; 124(12): 2739-44, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25042603

RESUMO

OBJECTIVES/HYPOTHESIS: The incidence of human papillomavirus (HPV)-driven disease beyond the oropharynx varies greatly in the reported literature. STUDY DESIGN: Case series. METHODS: Two hundred twenty-one samples were strictly classified to the subsites of oral cavity, larynx, or hypopharynx at the time of primary surgery. Formalin-fixed paraffin-embedded samples were subjected to a validated, tiered, diagnostic algorithm of p16 immunohistochemistry, high-risk HPV in situ hybridization, and quantitative polymerase chain reaction for HPV E6 DNA. An additional 60 oropharyngeal cases acted as an internal biological control. RESULTS: An incidence of 4% of HPV-driven cases was observed across the subsites outside the oropharynx compared to 70% of tumors confined within it. CONCLUSIONS: This is the first reporting of a broad range of nonoropharyngeal HPV rates using this validated diagnostic algorithm. It remains unclear whether patients with HPV-driven disease originating outside the oropharynx enjoy the same survival advantage apparent in those patients with oropharyngeal squamous cell carcinomas. LEVEL OF EVIDENCE: 4 Laryngoscope, 124:2739-2744, 2014.


Assuntos
Carcinoma de Células Escamosas/diagnóstico , Neoplasias de Cabeça e Pescoço/diagnóstico , Papillomaviridae/genética , Infecções por Papillomavirus/diagnóstico , Biomarcadores Tumorais/análise , DNA Viral/análise , Diagnóstico Diferencial , Feminino , Seguimentos , Humanos , Imuno-Histoquímica , Hibridização In Situ , Masculino , Pessoa de Meia-Idade , Orofaringe , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/virologia , Reação em Cadeia da Polimerase , Reação em Cadeia da Polimerase em Tempo Real , Estudos Retrospectivos , Carcinoma de Células Escamosas de Cabeça e Pescoço
4.
Otolaryngol Head Neck Surg ; 144(1): 29-35, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21493383

RESUMO

OBJECTIVE: Head and neck squamous cell carcinoma (HNSCC) patients with N3 neck disease at presentation are the minority. Prognosis for such patients is poor, but there is disagreement about which treatment policy is best adopted. The aim of this study was to identify which groups of patients are best offered radical treatment, examining factors of association, prognosis, and survival. STUDY DESIGN: Prospective cohort study. SETTING: Regional tertiary head and neck cancer unit. SUBJECTS AND METHODS: Data were collected prospectively from patients treated for HNSCC with N3 nodal disease between 1975 and 2005. The data collected included age, sex, tumor TNM stage, histological grade, treatment, and survival. Odds ratio was used to calculate whether each parameter was statistically significant. Tumor-specific and observed survival curves were also calculated. RESULTS: A total of 275 patients had N3 disease. Multivariate analysis confirmed that advanced disease at the primary site (odds ratio = 4.6, P = .0261) mitigated against curative treatment. Comparison of tumor-specific survival between curative and palliative treatment strategies suggests that aggressive treatment is associated with greatly improved survival (median survival = 1.45 years, 95% confidence interval [CI] = 1.23-1.67 years; 5-year survival = 26.6%, CI = 17.14%-36.06%) compared with those treated palliatively (median survival = 3.18 months, CI = 3.06-3.30 months; no 5-year survivors; P < .0001). CONCLUSION: A major factor in determining treatment strategies for N3 disease HNSCC is the extent of disease at the primary site. These data suggest that aggressive treatment of the neck improves survival and should be considered in these patients.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Carcinoma/mortalidade , Carcinoma/secundário , Carcinoma/terapia , Terapia Combinada , Seguimentos , Neoplasias de Cabeça e Pescoço/mortalidade , Neoplasias de Cabeça e Pescoço/secundário , Neoplasias de Cabeça e Pescoço/terapia , Humanos , Metástase Linfática , Estadiamento de Neoplasias , Neoplasias de Células Escamosas/mortalidade , Neoplasias de Células Escamosas/secundário , Neoplasias de Células Escamosas/terapia , Estudos Prospectivos , Carcinoma de Células Escamosas de Cabeça e Pescoço , Taxa de Sobrevida/tendências , Fatores de Tempo , Reino Unido/epidemiologia
5.
Auris Nasus Larynx ; 38(3): 381-6, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21277126

RESUMO

OBJECTIVES: To test the validity of the comparative audit tool of POSSUM (Physiological and Operative Severity Score for the Enumeration of Mortality and Morbidity) against a cohort of 92 consecutive laryngectomies at a major tertiary referral centre for head and neck cancer. The major outcome measurements were 30-day mortality rates, formation of a pharyngo-cutaneous fistula, and length of hospital stay. METHODS: By means of a prospective and retrospective case note analysis. RESULTS: No significant difference between the mean POSSUM morbidity scores of those patients who did, or did not develop a fistula, was found (p=0.535, 95% C.I. -4.36 to 8.33). No significant correlation was observed between POSSUM predicted morbidity and bed occupancy [r=0.137 (95% C.I. -0.070 to 0.334)]. The Portsmouth POSSUM equation for mortality however did accurately predict the mortality rate (observed to expected ratio of 1.05). CONCLUSION: The authors propose that whilst there are many similar factors linked to mortality between cohorts of general surgical and head and neck patients, there are several highly specific risk factors in open surgery of the upper aero-digestive tract in the head and neck which are linked with wound breakdown and morbidity which are omitted from the POSSUM scoring system. The authors warn against the use of this comparative audit tool in its current state for such surgical procedures and recommend the creation of a specific POSSUM for head and neck cancer surgery.


Assuntos
Neoplasias Laríngeas/mortalidade , Neoplasias Laríngeas/cirurgia , Laringectomia/mortalidade , Complicações Pós-Operatórias/mortalidade , Medição de Risco/estatística & dados numéricos , Índice de Gravidade de Doença , Adulto , Idoso , Idoso de 80 Anos ou mais , Fístula Cutânea/mortalidade , Inglaterra , Feminino , Fístula/mortalidade , Humanos , Tempo de Internação/estatística & dados numéricos , Masculino , Auditoria Médica/estatística & dados numéricos , Pessoa de Meia-Idade , Doenças Faríngeas/mortalidade , Faringe/cirurgia , Estudos Prospectivos , Estudos Retrospectivos , Análise de Sobrevida
6.
Eur Arch Otorhinolaryngol ; 263(12): 1061-4, 2006 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-17004088

RESUMO

Intratympanic membrane cholesteatoma, occurring in the absence of trauma or surgery to the ear, is rare with less than 20 cases reported in the literature. We report a rare incidental finding of intratympanic membrane cholesteatoma in a 12-month-old girl and review the literature.


Assuntos
Colesteatoma da Orelha Média/diagnóstico , Membrana Timpânica/patologia , Adolescente , Adulto , Criança , Pré-Escolar , Colesteatoma da Orelha Média/cirurgia , Feminino , Humanos , Lactente , Masculino , Otoscopia , Membrana Timpânica/cirurgia
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