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1.
Clin Oncol (R Coll Radiol) ; 33(10): e442-e449, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34261594

RESUMO

AIMS: In the current eighth edition head and neck TNM staging, extranodal extension (ENE) is an adverse feature in oral cavity squamous cell cancer (OSCC). The previous seventh edition N1 with ENE is now staged as N2a. Seventh edition N2+ with ENE is staged as N3b in the eighth edition. We evaluated its potential impact on patients treated with surgery and postoperative intensity-modulated radiotherapy (IMRT). MATERIALS AND METHODS: OSCC patients treated with primary surgery and adjuvant (chemo)radiotherapy between January 2005 and December 2014 were reviewed. Cohorts with pathological node-negative (pN-), pathological node-positive without ENE (pN+_pENE-) and pathological node-positive with ENE (pN+_pENE+) diseases were compared for local control, regional control, distant control and overall survival. The pN+ cohorts were further stratified into seventh edition N-staging subgroups for outcomes comparison. RESULTS: In total, 478 patients were evaluated: 173 pN-; 159 pN+_pENE-; 146 pN+_pENE+. Outcomes at 5 years were: local control was identical (78%) in all cohorts (P = 0.892), whereas regional control was 91%, 80% and 68%, respectively (P < 0.001). Distant control was 97%, 87%, 68% (P < 0.001) and overall survival was 75%, 53% and 39% (P < 0.001), respectively. Overall survival for N1 and N2a subgroups was not significantly different. In the seventh edition N2b subgroup of pENE- (n = 79) and pENE+ (n = 79) cohorts, overall survival was 67% and 37%, respectively. In the seventh edition N2c subgroups, overall survival for pENE- (n = 17) and pENE+ (n = 38) cohorts was 65% and 35% (P = 0.08), respectively. Overall, an additional 128 patients (42% pN+) were upstaged as N3b. CONCLUSIONS: When eighth edition staging was applied, stage migration across the N2-3 categories resulted in expected larger separations of overall survival by stage. Patients treated with primary radiation without surgical staging should have outcomes carefully monitored. Strategies to predict ENE preoperatively and trials to improve the outcomes of pENE+ patients should be explored.


Assuntos
Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Humanos , Neoplasias Bucais/patologia , Neoplasias Bucais/radioterapia , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos
2.
J Otolaryngol Head Neck Surg ; 45(1): 61, 2016 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-27876067

RESUMO

BACKGROUND: Neck metastasis is the most important prognostic factor in oral cavity squamous cell carcinomas (SCC). Apart from the T- stage, depth of invasion has been used as a highly predictable factor for microscopic neck metastasis, despite the controversy on the exact depth cut off point. Depth of invasion can be determined clinically and radio logically. However, there is no standard tool to determine depth of invasion preoperatively. Although MRI is used widely to stage the head and neck disease, its utility in depth evaluation has not formally been assessed. OBJECTIVE: To compare preoperative clinical and radiological depth evaluation in oral tongue SCC using the standard pathological depth. To compare clinical and radiological accuracy between superficial (<5 mm) vs. deep invaded tumor (≥5 mm) METHODS: This prospective study used consecutive biopsy-proven oral tongue invasive SCC that presented to the University health network (UHN), Toronto. Clinical examination, radiological scan and appropriate staging were determined preoperatively. Standard pathology reports postoperatively were reviewed to determine the depth of invasion from the tumor specimen. RESULTS: 72 tumour samples were available for analysis and 53 patients were included. For all tumors, both clinical depth (r = 0.779; p < 0.001) and radiographic depth (r =0.907; p <0.001) correlated well with pathological depth, with radiographic depth correlating slightly better. Clinical depth also correlated well with radiographic depth (r = 0.731; p < 0.001). By contrast, for superficial tumors (less than 5 mm on pathological measurement) neither clinical (r = 0.333, p = 0.34) nor radiographic examination (r = - 0.211; p = 0.56) correlated with pathological depth of invasion. CONCLUSION: This is the first study evaluating the clinical assessment of tumor thickness in comparison to radiographic interpretation in oral cavity cancer. There are strong correlations between pathological, radiological, and clinical measurements in deep tumors (≥5 mm). In superficial tumors (<5 mm), clinical and radiological examination had low correlation with pathological thickness.


Assuntos
Carcinoma de Células Escamosas/diagnóstico por imagem , Carcinoma de Células Escamosas/secundário , Neoplasias de Cabeça e Pescoço/diagnóstico por imagem , Neoplasias de Cabeça e Pescoço/secundário , Imageamento por Ressonância Magnética/métodos , Invasividade Neoplásica/diagnóstico por imagem , Invasividade Neoplásica/patologia , Neoplasias da Língua/diagnóstico por imagem , Neoplasias da Língua/patologia , Idoso , Biópsia , Feminino , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Estudos Prospectivos , Sensibilidade e Especificidade
3.
Virchows Arch ; 468(3): 305-12, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26710792

RESUMO

Myoepithelial carcinoma (MCA) is a rare malignancy of salivary glands that was included in the WHO Classification of Head and Neck Tumors in 1991. MCA has shown a broad spectrum of clinical outcomes, but attempts to identify prognostic markers for this malignancy have not resulted in significant progress. Conventional histopathological characteristics such as tumour grade, nuclear atypia, mitotic index and cell proliferation have failed to predict the outcome of MCA. In this study, we reviewed the histopathology of 19 cases of MCA focusing on nuclear atypia, mitotic count, tumour necrosis, nerve and vascular invasion and occurrence of a pre-existing pleomorphic adenoma in connection to the MCA. Histopathological characteristics and clinical information were correlated with the immunohistochemical expression of cell cycle proteins including c-Myc, p21, Cdk4 and Cyclin D3. The proportion of tumour cells immunoreactive for these markers and their intensity of staining were correlated with clinical information using logistic regression, Kaplan-Meier and Cox regression. Using logistic regression analysis, cytoplasmic c-Myc expression was associated with the occurrence of metastases (P = 0.019), but limitations of semi-quantitation of immunostaining and the limited number of cases preclude definitive conclusions. Our data show that the occurrence of tumour necrosis predicts poor disease-free survival in MCA (P = 0.035).


Assuntos
Proteínas de Ciclo Celular/metabolismo , Mioepitelioma/patologia , Recidiva Local de Neoplasia/patologia , Neoplasias das Glândulas Salivares/patologia , Adenoma Pleomorfo/patologia , Adulto , Idoso , Biomarcadores Tumorais/análise , Feminino , Humanos , Imuno-Histoquímica/métodos , Masculino , Pessoa de Meia-Idade , Mioepitelioma/química , Mioepitelioma/metabolismo , Mioepitelioma/mortalidade , Recidiva Local de Neoplasia/diagnóstico , Recidiva Local de Neoplasia/mortalidade , Prognóstico , Neoplasias das Glândulas Salivares/química , Neoplasias das Glândulas Salivares/metabolismo
4.
Oral Oncol ; 47(1): 45-50, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21167767

RESUMO

BACKGROUND: Tobacco smoking and high alcohol consumption are considered major risk factors of oral tongue squamous cell carcinoma. This study compared disease outcome between patients with and without known risk factors. METHODS: Patients with oral tongue squamous cell carcinoma treated at two major medical centers from 1994 to 2008 were identified by cancer registry search. The medical files were reviewed for background-and-disease-related data, risk factors, and outcome. RESULTS: The study sample consisted of 291 patients: 175 had a history of heavy tobacco smoking and alcohol abuse and 116 did not. Comparison of the patients without risk factors between the two centers yielded no differences in background features. Men accounted for 74% of the total patients with risk factors and comprised 77% of the risk-factor group. The risk-factor group was characterized by a significantly higher mean tumor grade (p=0.0001) and greater tumor depth of invasion (p=0.022) than the non-risk-factor group. The 5-year local and regional control rates were 85.3% and 74%, respectively, with no significant difference between the groups. The 5-year overall survival rate was 68% in the risk-factor group and 64% in the non-risk-factor group (p=NS). Separate analysis of patients aged <40 years at diagnosis revealed a worse overall (p=0.015) and disease-free survival (p=0.038) in those without risk factors. CONCLUSIONS: The outcome of oral tongue carcinoma is similar in patients with and without risk factors. The worse prognosis in younger patients (<40 years) without risk factors suggests that the pathogenesis in these cases involves factors other than smoking and alcohol.


Assuntos
Consumo de Bebidas Alcoólicas/efeitos adversos , Carcinoma de Células Escamosas/patologia , Recidiva Local de Neoplasia/patologia , Fumar/efeitos adversos , Neoplasias da Língua/patologia , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/etiologia , Carcinoma de Células Escamosas/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/mortalidade , Fatores de Risco , Taxa de Sobrevida , Neoplasias da Língua/etiologia , Neoplasias da Língua/mortalidade , Resultado do Tratamento , Adulto Jovem
5.
Cell Death Differ ; 16(11): 1469-79, 2009 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-19575017

RESUMO

Overexpression of BMI1 correlates with cancer development, progression, and therapy failure; however, the underlying molecular mechanisms remain to be fully elucidated. Using the C666-1 nasopharyngeal cancer (NPC) model, the role of BMI1 in mediating response of NPC cells to radiation therapy (RT) was investigated. The results showed a novel radioresistance function for BMI1 in NPC, wherein BMI1 depletion sensitized NPC cells to RT. Cell cycle analysis and transmission electron microscopy (TEM) showed apoptosis as the major mode of cell death, and the mitochondria as a primary targeted cellular organelle. Genome-wide microarray and pathway analyses revealed that the P53 pathway is a critical mediator of this process. Cotransfection with siP53 rescued C666-1 cells from cytotoxicity upon BMI1 depletion and RT, thereby corroborating the role for P53. Pretreatment with the antioxidant, Trolox, inhibited apoptosis, indicating that production of reactive oxygen species (ROS) is also mediating cytotoxicity. In vivo, BMI1 depletion combined with RT abrogated tumor-forming capacity in SCID mice, showing the relevance of this process in a more complex tumor environment. Hence, we show a novel role for BMI1 in conferring radioresistance in cancer cells through the downregulation of p53-mediated apoptosis. These results suggest a potential strategy of BMI1 depletion combined with RT for tumors wherein BMI1 appears to be driving disease progression.


Assuntos
Apoptose , Neoplasias Nasofaríngeas/radioterapia , Proteínas Nucleares/fisiologia , Proteínas Proto-Oncogênicas/fisiologia , Proteínas Repressoras/fisiologia , Proteína Supressora de Tumor p53/metabolismo , Animais , Cromanos/farmacologia , Progressão da Doença , Perfilação da Expressão Gênica , Técnicas de Silenciamento de Genes , Histonas/metabolismo , Humanos , Camundongos , Análise em Microsséries , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Complexo Repressor Polycomb 1 , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas/metabolismo , RNA Mensageiro/metabolismo , RNA Interferente Pequeno , Espécies Reativas de Oxigênio/metabolismo , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismo , Transplante Heterólogo , Células Tumorais Cultivadas , Proteína Supressora de Tumor p53/genética
6.
Br J Cancer ; 96(9): 1425-32, 2007 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-17437012

RESUMO

The Pidd (p53-induced protein with death domain) gene was shown to be induced by the tumour suppressor p53 and to mediate p53-dependent apoptosis in mouse and human cells, through interactions with components of both the mitochondrial and the death receptor signalling pathways. To study the role of Pidd in clinical tumours, we measured its expression by quantitative reverse transcription-PCR in microdissected oral squamous cell carcinomas (OSCC) with and without p53 mutation. Tumour cell apoptosis was assessed by in situ terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling. Tumour proliferation was assessed by immunohistochemical staining for the Ki-67 antigen. We found a wide range of Pidd expression among OSCC. Statistical analysis revealed an association between Pidd expression and apoptotic index (Mann-Whitney test, P<0.001), consistent with a role of Pidd in apoptosis in this tumour type. Furthermore, we showed a positive correlation between apoptotic index and proliferative index that has not been previously described for OSCC. There was no correlation between Pidd expression and the p53 mutation status of these tumours, suggesting that Pidd expression may be regulated by p53-independent mechanisms. Further characterisation of these molecular defects in the control of proliferation and apoptosis should help in developing treatments that target OSCC according to their biological properties.


Assuntos
Carcinoma de Células Escamosas/patologia , Proteínas de Transporte/genética , Neoplasias Bucais/patologia , Proteína Supressora de Tumor p53/genética , Apoptose , Carcinoma de Células Escamosas/genética , Divisão Celular , Proteínas Adaptadoras de Sinalização de Receptores de Domínio de Morte , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Bucais/genética , Estadiamento de Neoplasias , Reação em Cadeia da Polimerase , RNA Neoplásico/genética , RNA Neoplásico/isolamento & purificação
7.
Clin Otolaryngol ; 32(1): 19-23, 2007 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-17298305

RESUMO

OBJECTIVES: Squamous cell carcinoma of the nasal vestibule is rare variant of skin cancer. The TNM classification for skin cancer has been used, whereas, Wang has devised an independent staging system, which he stated was more accurate. The purpose of this study was to analyse the prognostic indicators for survival in a patients with nasal vestibule cancer from the Princess Margaret Hospital, Toronto. DESIGN: A retrospective review of case notes from the Princess Margaret Hospital archives was performed. SETTING: The Princess Margaret Hospital/Ontario Cancer Institute is the tertiary regional Head and Neck Oncology Centre for ON, Canada. PARTICIPANTS: All patients with nasal vestibule cancer (ICD10 C300) were included. MAIN OUTCOME MEASURES: Univariate and multivariate analyses were performed and Kaplan-Meier survival curves constructed. RESULTS: Eighty-four patients were identified. The mean age was 67, there was a male preponderance of 2 : 1. Primary radical radiation was used in 77% of patients. Age (P = 0.02), N stage (P = 0.0001) and Wang classification (P = 0.0001) were associated with prediction of overall survival using multivariate analysis. Grade, depth of invasion and N stage were associated with disease-free survival outcome. A 5-year overall survival rate of 58% and disease-free survival of 52% was seen. CONCLUSION: Nasal vestibule cancer behaves in a more aggressive manner than any other skin cancers affecting the head and neck. The Wangs' classification appears to be a better prognostic indicator for overall survival then the TNM classification for skin cancer.


Assuntos
Carcinoma de Células Escamosas/mortalidade , Neoplasias Nasais/mortalidade , Idoso , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/terapia , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Masculino , Estadiamento de Neoplasias , Neoplasias Nasais/patologia , Neoplasias Nasais/terapia , Ontário/epidemiologia , Prognóstico , Radioterapia Adjuvante , Estudos Retrospectivos , Rinoplastia/métodos , Taxa de Sobrevida/tendências
8.
Br J Plast Surg ; 56(2): 92-9, 2003 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-12791349

RESUMO

Osteoradionecrosis (ORN) of the craniomaxillofacial skeleton is a serious and debilitating complication that can occur following radiation therapy in the head and neck. Patients require effective treatment, which eradicates diseased tissue and restores function with minimal additional morbidity in a single stage, a requirement fulfilled in many cases by free tissue transfer. In a 6-year period from 1994 to 1999, 21 patients with ORN were treated by wide resection and free-flap reconstruction. The median interval between radiation therapy and ORN was 4 years (range: 1-33 years). The median radiation dose was 6000cGy. The affected areas were the mandible (15 patients), the temporal bone (three patients), the maxilla (one patient), the cervical vertebrae (one patient) and the frontal bone (one patient). Clinical symptoms included pain, ulceration, a persistent draining fistula, exposure of bone or hardware, and pathological fracture or non-union of bone. Six patients had had previous unsuccessful attempts at conservative surgical resection. Ten patients had preoperative hyperbaric oxygen (HBO) therapy. A number of different flaps were used for reconstruction in these patients. These included free fibula flaps (13 patients), iliac crest flaps (two patients), scapula flaps (three patients) and rectus abdominis flaps (three patients). All patients achieved relief from their presenting symptoms and primary bone or wound healing. One flap (4.8%) was lost. This was successfully reconstructed in a subsequent procedure. There were three flap re-explorations, two for arterial thrombosis and one for venous thrombosis. Conservative measures, such as limited debridement and HBO therapy, may be effective in preventing the progression of ORN. However, they fail to eradicate established ORN, which requires radical surgical resection followed by functional reconstruction with well-vascularised tissue.


Assuntos
Osteorradionecrose/terapia , Crânio , Idoso , Ossos Faciais/efeitos da radiação , Feminino , Neoplasias de Cabeça e Pescoço/radioterapia , Humanos , Oxigenoterapia Hiperbárica , Masculino , Mandíbula/efeitos da radiação , Maxila/efeitos da radiação , Pessoa de Meia-Idade , Crânio/efeitos da radiação , Retalhos Cirúrgicos
9.
Arch Facial Plast Surg ; 3(4): 241-4, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-11710857

RESUMO

OBJECTIVE: To determine, using patient- and observer-rated facial disfigurement measures, whether a lateral rhinotomy imparts significant aesthetic morbidity. DESIGN: Retrospective and subject-controlled study in a large, tertiary-referral, academic otolaryngology department. Twenty-one consecutive patients who had undergone lateral rhinotomy for the treatment of inverted papilloma were studied in the long-term. MAIN OUTCOME MEASURES: Scores on the following: (1) the novel Patient-Rated Facial Disfigurement Analogue Scale questionnaire and (2) the reliable and validated Observer-Rated Facial Disfigurement 9-Point Likert Scale. RESULTS: Patients rated their facial appearance as minimally altered and significantly less apparent to others. The observers in this study, a surgeon (J.C.I.) and a psychiatrist (M.R.K.), rated the patients' facial disfigurement as minimally visible. Patients seem to rate how apparent their appearance is to others in a similar fashion to observers. The observer-rated facial disfigurement scale used is valid and reliable. CONCLUSION: Patient- and observer-rated facial disfigurement measures suggest that a lateral rhinotomy does not impart significant aesthetic morbidity.


Assuntos
Estética , Face , Neoplasias Nasais/cirurgia , Nariz/cirurgia , Autoimagem , Adulto , Idoso , Atitude do Pessoal de Saúde , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Papiloma Invertido/cirurgia , Estudos Retrospectivos
10.
Head Neck ; 23(10): 916-22, 2001 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11592240

RESUMO

BACKGROUND: Nasopharyngectomy is emerging as an important treatment option for salvaging locally recurrent nasopharyngeal carcinoma (NPC). After nasopharyngectomy, resurfacing the nasopharynx and covering the internal carotid artery is important to minimize the risk of infection, osteoradionecrosis, and carotid rupture. Previous authors have advocated the use of free grafts of skin and mucosa for this purpose but have also described significant rates of partial and total graft failure. METHODS: We believe that the best and most reliable way to resurface the nasopharynx is with vascularized tissue, and our preference is for the use of a free radial forearm flap. To illustrate our approach, we present two patients who underwent nasopharyngectomy by means of a maxillary swing approach and who had resurfacing of the surgical defect with a free radial forearm flap. RESULTS: Both patients had complete en bloc resection of tumor followed by the insetting of a free radial forearm flap to reline the surgical defect. Both flaps remained completely viable, and both patients achieved successful resurfacing of the entire nasopharynx. The morbidity of surgery was minimal, and there were no perioperative complications. On assessment 1 year later, the free radial forearm flap continues to reline the entire neonasopharynx, and the long-term functional recovery after surgery is excellent. CONCLUSION: Resurfacing the nasopharynx after nasopharyngectomy with a free radial forearm flap aids healing and minimizes the risk of complications. The morbidity of surgery is minimal and the functional recovery is excellent.


Assuntos
Neoplasias Nasofaríngeas/cirurgia , Nasofaringe/cirurgia , Faringectomia , Retalhos Cirúrgicos , Humanos , Excisão de Linfonodo , Masculino , Pessoa de Meia-Idade , Neoplasias Nasofaríngeas/diagnóstico por imagem , Nasofaringe/diagnóstico por imagem , Tomografia Computadorizada por Raios X
11.
Int J Radiat Oncol Biol Phys ; 51(2): 332-43, 2001 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-11567806

RESUMO

PURPOSE: Ipsilateral techniques designed to restrict treatment to the primary tumor and neck on the same side have been used in selected cases of cases of carcinoma of the tonsillar region at our institution for many years. The primary purpose of this study is to evaluate the risk of failure in the opposite neck in cases selected for unilateral radiotherapy over a 21-year period. METHODS AND MATERIALS: Ipsilateral radiotherapy techniques were used in 228 of 642 patients with carcinoma of the tonsillar region from 1970 to 1991. Local control, regional lymph-node control (including contralateral failure), and survival were calculated for different degrees of tumor extent treated with these techniques. RESULTS: Mean follow-up was 7 years. Cases tended to be T1 and T2, with N0 disease. The 3-year actuarial local control rate was 77% and cause-specific survival was 76%. Opposite neck failure was seen in 8 patients (crude rate of 3.5%). In the earlier period of the study, primary coverage was problematic in a proportion of cases and resulted in higher rates of local failure. CONCLUSION: Appropriately selected cases of carcinoma of the tonsil show minimal risk of failure in the opposite neck with ipsilateral techniques. Patients should undergo computed tomography planning to ensure adequate target coverage.


Assuntos
Glândula Parótida/efeitos da radiação , Neoplasias Tonsilares/radioterapia , Xerostomia/prevenção & controle , Adulto , Idoso , Idoso de 80 Anos ou mais , Radioisótopos de Cobalto/uso terapêutico , Intervalo Livre de Doença , Elétrons/uso terapêutico , Feminino , Seguimentos , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias/métodos , Segunda Neoplasia Primária/patologia , Glândula Parótida/patologia , Fótons/uso terapêutico , Lesões por Radiação/patologia , Dosagem Radioterapêutica , Neoplasias Tonsilares/patologia , Falha de Tratamento
12.
Int J Cancer ; 93(3): 353-60, 2001 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-11433399

RESUMO

The most prevalent risk factors in the development of head-and-neck squamous-cell carcinoma (HNSCC) are excessive tobacco and alcohol consumption. In young patients with HNSCC, these risk factors are often absent. Our purpose was to investigate the risk factors, microsatellite instability (MSI) changes and status of the mismatch repair genes hMLH1 and hMSH2 in a cohort of young patients with HNSCC. Fifty-seven HNSCC tumors were examined for the presence of MSI at 16 microsatellite sites using PCR. In the young patient group (24 cases, < or = 44 years old), 100% of tumors had MSI at 1 site at least and 88% had MSI at 2 or more loci. In older patients (33 cases, > or = 45 years), MSI at 1 or more sites was found in 61% of tumors (young vs. old, p = 0.0003) and instability at 2 or more sites was found in 36% of tumors (young vs. old, p = 0.0001). The involvement of the mismatch repair genes was investigated by examining promoter methylation, exon mutation and gene expression of hMLH1 and hMSH2. All results were negative, indicating that inactivation of these 2 genes does not play a role in the development of MSI in tumors from this patient group. Furthermore, the young patient group had a significantly lower incidence of smoking (46% young, 88% old; p = 0.001) and alcohol consumption (33% young, 67% old; p = 0.0169), emphasizing the probable importance of other environmental and/or genetic factors in the development of their disease.


Assuntos
Carcinoma de Células Escamosas/genética , DNA de Neoplasias/genética , Proteínas de Ligação a DNA , Neoplasias de Cabeça e Pescoço/genética , Repetições de Microssatélites/genética , Mutação , Proteínas de Neoplasias/genética , Proteínas Proto-Oncogênicas/genética , Proteínas Adaptadoras de Transdução de Sinal , Adulto , Idoso , Idoso de 80 Anos ou mais , Proteínas de Transporte , Primers do DNA/química , Feminino , Humanos , Técnicas Imunoenzimáticas , Masculino , Metilação , Pessoa de Meia-Idade , Proteína 1 Homóloga a MutL , Proteína 2 Homóloga a MutS , Proteínas de Neoplasias/metabolismo , Proteínas Nucleares , Reação em Cadeia da Polimerase , Polimorfismo Conformacional de Fita Simples , Regiões Promotoras Genéticas , Proteínas Proto-Oncogênicas/metabolismo , Análise de Sequência de DNA , Pele/metabolismo
13.
Oncogene ; 20(5): 654-8, 2001 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-11313998

RESUMO

Oral squamous cell carcinoma (OSCC) is associated with heavy smoking and drinking, but the molecular pathway of tumorigenesis is not understood. Inactivation of the p53 tumor suppressor gene is likely to play an important role since p53 mutation is frequently found. The p14ARF tumor suppressor gene is functionally linked to p53, because it is activated by oncogenes and causes p53-dependent growth arrest and apoptosis. The relationship between p14ARF and p53 inactivation has not been described for OSCC. We studied 25 cases of OSCC to determine if there is an inverse correlation between p53 mutation and p14ARF inactivation by homozygous deletion or mutation. p53 mutation was found in 16 of 25 cases (64%), including nine missense and seven truncating mutations. While all cases with missense mutations showed abnormal accumulation of p53 protein, there were also five carcinomas which showed increased p53 staining in the absence of mutation. p14ARF deletion or mutation was found in eight cases (32%), six of which also demonstrated p53 mutation. Our findings indicate that OSCC often involves loss of both p14ARF and p53 function and suggest that inactivation of these two tumor suppressor genes are not functionally equivalent during tumorigenesis.


Assuntos
Carcinoma de Células Escamosas/genética , Genes p53/genética , Neoplasias Bucais/genética , Proteínas/genética , Neoplasias da Língua/genética , Adulto , Idoso , Carcinoma de Células Escamosas/metabolismo , Éxons/genética , Feminino , Mutação da Fase de Leitura , Deleção de Genes , Regulação Neoplásica da Expressão Gênica , Inativação Gênica , Genes p16/genética , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/metabolismo , Mutação de Sentido Incorreto , Proteínas/fisiologia , Neoplasias da Língua/metabolismo , Proteína Supressora de Tumor p14ARF , Proteína Supressora de Tumor p53/metabolismo
14.
Int J Radiat Oncol Biol Phys ; 49(5): 1235-8, 2001 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-11286828

RESUMO

PURPOSE: Carcinoma-in-situ (CIS) of the vocal cords frequently progresses to invasive disease if untreated. Treatment approaches include vocal cord stripping, radiation therapy (RT), and laser excision. The purpose of this analysis was to assess the efficacy and safety of a standard RT regimen in the treatment of this condition. METHODS AND MATERIALS: Between January 1980 and December 1994, 67 patients (52 men, 15 women; median age, 65 years) with glottic CIS were treated with RT. The standard RT regimen was 51 Gy in 20 fractions given over 4 weeks (99% of patients). Prior to receiving RT, 21 patients (31%) had undergone 1 or 2 vocal cord stripping procedures, and 1 had been treated with laser. RESULTS: With a median follow-up of 6.5 years, 1 patient developed invasive glottic cancer, giving a 5-year actuarial local control rate of 98%. This patient recurred 14 months after treatment and was salvaged with laryngectomy. He is currently free of disease 2 years after surgery. There were no serious acute or late treatment complications. Sixteen patients (24%) developed subsequent malignancies, 8 of these being in the upper aerodigestive tract, although none were in the radiation field. CONCLUSIONS: Moderate-dose radiation therapy is an effective treatment for glottic CIS. It is well tolerated, produces no serious acute or long-term side effects, with an excellent cure rate.


Assuntos
Carcinoma in Situ/radioterapia , Neoplasias Laríngeas/radioterapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma in Situ/mortalidade , Feminino , Seguimentos , Glote , Humanos , Neoplasias Laríngeas/mortalidade , Masculino , Pessoa de Meia-Idade , Análise de Sobrevida , Resultado do Tratamento
15.
J Otolaryngol ; 30(2): 102-5, 2001 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-11770951

RESUMO

OBJECTIVES: Multicentricity has been cited as a rationale for total thyroidectomy in patients with papillary thyroid carcinoma (PTC) confined to one lobe. The purpose of this study was to examine the incidence of multicentricity of PTC in a cohort of 165 patients with PTC confined to one lobe and to examine clinical and pathologic features that may help predict for the presence of contralateral disease. DESIGN: Retrospective review. SETTING: Tertiary care hospital. METHOD: A retrospective review of 165 patients with PTC confined to one lobe treated at the Toronto General Hospital from 1992 to 1997 was performed. MAIN OUTCOME MEASURE: The predictive factors affecting the presence of multicentricity of PTC were analyzed. RESULTS: The incidence of PTC present in the contralateral lobe was 56.3%. We were unable to find any correlation of multicentricity with age, sex, tumour size, extrathyroidal spread, thyroiditis, or tall cell variant of PTC. There were trends toward higher incidence of contralateral disease in those patients with a prior history of irradiation and those with lymphatic metastases, but these trends did not reach statistical significance. CONCLUSIONS: The incidence of contralateral disease in papillary thyroid cancer treated at the Toronto Hospital was 56.3%. There was a higher incidence of contralaterality in those patients with a previous history of irradiation and in those with lymphatogenous metastases, but this did not reach statistical significance.


Assuntos
Carcinoma Papilar/epidemiologia , Neoplasias da Glândula Tireoide/epidemiologia , Adulto , Feminino , Humanos , Incidência , Masculino , Estudos Retrospectivos , Tireoidectomia
16.
J Otolaryngol ; 30(2): 98-101, 2001 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-11770964

RESUMO

The sternocleidomastoid muscle flap may play a significant role in reducing the incidence of Frey's syndrome and maintaining facial contour after parotidectomy. Patients who underwent superficial parotidectomy from August 1992 to March 1999 were divided into two groups (N = 26). One group had sternocleidomastoid muscle flap reconstruction. A historical cohort study was designed with the two groups being matched for sex, age, pathology, postoperative radiation, date of surgery, and extent of dissection. The starch iodine test was used to evaluate for gustatory sweating, and the Observer Rated Disfigurement Scale was used to assess facial contour and aesthetics. The results of our study suggest that the sternocleidomastoid flap reconstruction following parotidectomy surgery does not alter the incidence of Frey's syndrome and does not significantly improve facial contour and aesthetics.


Assuntos
Glândula Parótida/cirurgia , Retalhos Cirúrgicos , Sudorese Gustativa/prevenção & controle , Estudos de Coortes , Face , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Satisfação do Paciente , Sudorese Gustativa/epidemiologia
17.
J Otolaryngol ; 30(1): 34-40, 2001 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-11770971

RESUMO

The pectoralis major myocutaneous pedicled flap (PMMPF) has been considered to be the "workhorse" of pedicled flaps for head and neck reconstruction, and several series of PMMPF procedures have been reported in the literature. Between 1983 and 1997, 244 reconstruction procedures using the PMMPF were carried out on 229 patients by the Otolaryngology-Head and Neck Surgery Department at the Toronto General Hospital. Pectoralis major myocutaneous pedicled flap reconstructions were completed after ablation of cancer in the following sites: oral cavity, 113; oropharynx/hypopharynx, 50; larynx, 59; and other, 21. The locations of reconstruction were oral cavity, 121; pharynx, 74; and neck or face, 50. Of the 244 cases, 202 were carried out as primary reconstructive procedures, whereas 42 flaps were "salvage" procedures (reconstruction after fistula, flap failure, osteoradionecrosis, and internal jugular vein rupture). Eighty-five cases (35%) were affected by complications such as dehiscence, infection, hematoma, seroma, partial flap failure, total flap failure, fistula, and donor site complications. The duration of admission for cases with complications was longer, and higher complication rates were associated with salvage procedures, number of comorbidities, number of pack-years of cigarettes smoked, and oral cavity reconstructions. This series of consecutive PMMPF procedures is the largest reported to date.


Assuntos
Neoplasias de Cabeça e Pescoço/cirurgia , Músculos Peitorais/transplante , Procedimentos de Cirurgia Plástica/estatística & dados numéricos , Retalhos Cirúrgicos/estatística & dados numéricos , Canadá , Hospitais Gerais , Humanos , Músculos Peitorais/cirurgia , Procedimentos de Cirurgia Plástica/efeitos adversos , Procedimentos de Cirurgia Plástica/métodos , Estudos Retrospectivos
18.
J Otolaryngol ; 30(5): 271-9, 2001 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11771019

RESUMO

PURPOSE: The optimal management of malignant parotid gland tumours remains to be defined precisely. Specifically, a further understanding of the tumour features that influence treatment outcome is needed. MATERIALS AND METHODS: A retrospective review was conducted on 184 patients who were registered at the Princess Margaret Hospital with a diagnosis of a primary malignant parotid gland tumour. RESULTS: All patients were initially managed with a parotidectomy, and postoperative x-ray radiation therapy (XRT) was administered to 159 patients. The actuarial 5-year cause-specific survival and locoregional control rates were 76% and 81%, respectively. The survival and locoregional control rates for patients treated with surgery alone versus surgery plus postoperative XRT were not statistically different. A multiple regression analysis identified only age and tumour category to be independently significant prognostic factors for both survival and locoregional control. CONCLUSION: We would recommend that patients with malignant parotid gland tumours be managed with parotidectomy, followed by postoperative XRT for tumours with residual disease, aggressive histology, and/or positive lymph nodes.


Assuntos
Neoplasias Parotídeas/terapia , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Inglaterra/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/epidemiologia , Glândula Parótida/cirurgia , Neoplasias Parotídeas/mortalidade , Neoplasias Parotídeas/patologia , Modelos de Riscos Proporcionais , Radioterapia Adjuvante , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento
20.
Laryngoscope ; 110(12): 2056-60, 2000 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-11129020

RESUMO

OBJECTIVES/HYPOTHESIS: Reconstruction of the mandible and oral cavity after segmental resection is a challenging surgical problem. Although osteocutaneous free flaps are generally accepted to be optimal for reconstruction of anterior defects, the need for bony reconstruction for a pure lateral mandibular defect remains controversial. STUDY DESIGN: A retrospective study. METHODS: A retrospective comparative study of short- and long-term outcomes of three different reconstruction techniques for lateral defects was performed. In total, 57 patients were included, of whom 27 had a plate and pedicled pectoralis major myocutaneous flap (PMMF group), 16 had a plate and free radial forearm flap (FRFF group), and 14 had an osteocutaneous free flap. Functionality, flap failure, and complications were scored. RESULTS: Plates had to be removed in 7 of the 27 patients in the PMMF group and 2 of the 16 in the FRFF group; none of the 14 osteocutaneous free flaps failed. The difference was of borderline statistical significance (P = .055). Longterm functional outcome revealed no statistically significant difference in oral deglutition (P = .76) or in facial contour (P = .36). Oral continence was significantly better in patients in the FRFF group (88%) as compared with the PMMF group (52%) or the osteocutaneous free flap group (43%) (P = .02). On the other hand, the results for speech favored the osteocutaneous free flap group; 13 of 14 patients (92.9%) had a normal score compared with 12 of 16 patients (75%) in the FRFF group and 17 of 27 (63%) in the PMMF group. However, this represented a borderline statistically significant result (P = .06). CONCLUSIONS: For lateral mandibular defects, the osteocutaneous free flap is reliable and durable in the long term. However, in a selected group of patients either of the two flap-plate options is a viable reconstructive option.


Assuntos
Carcinoma de Células Escamosas/cirurgia , Neoplasias Mandibulares/cirurgia , Procedimentos de Cirurgia Plástica , Retalhos Cirúrgicos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento
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