Inmunoterapia para el tratamiento del cáncer de cabeza y cuello ¿dónde estamos y hacia dónde vamos? / Immunotherapy for the treatment of head and neck cancer: where are we and where are we going?

El cáncer de cabeza y cuello comprende a todos aquellos tumores que se desarrollan en el tracto aerodigestivo superior, una de las características de éstos es su diversidad, que no es solo desde el punto de vista histológico y etiológico, sino que incluyen diversas formas de presentación, progresión y enfoques terapéuticos. Son de causa multifactorial, siendo el alcohol y el tabaco los principales factores de riesgo asociados; en los últimos años se ha relacionado a ciertos virus con potencial oncogénico con la génesis tumoral, entre ellos al Virus del Papiloma Humano, lo que ha permitido modificar el sistema de estadificación tumor primario-nodos linfáticos cancerosos-metástasis (TNM); presentándolo ahora en dos grandes grupos acorde a la Proteína supresora de tumores P16: P16+ y P16-,los cuales tienen características y manejo diferente. En vista de la heterogeneidad de la enfermedad, son diversos los tratamientos que se ha empleados para el manejo de la misma, entre ellos cirugía, radioterapia, quimioterapia e/o inmunoterapia; ésta última terapéutica, está dirigida hacia la estimulación del sistema inmune del paciente con la finalidad de generar la destrucción de las células tumorales, se realizan previo a una intervención quirúrgica para reducir el tamaño del tumor. Una forma destacable, es la del bloqueo de puntos de control inmunitarios, especialmente hacia proteínas de control inmune moduladoras de respuesta de células T, como los anti-PD-1 y los anti-CTLA-4. La inmunoterapia cada vez va tomando más protagonismo en oncología, en especial las formas de evasión de las reacciones inmunitarias por parte de las células cancerígenas(AU)

Head and neck cancer includes all those tumors that develop in the upper aerodigestive tract, one of the characteristics of these is their heterogeneity, which is not only from the histological and etiological, but also include various forms of presentation, progression and therapeutic approaches.They have a multifactorial cause, with alcohol and tobacco being the main associated risk factors, however, in recent year scertain viruses with oncogenic potential have been linked to tumor genesis, including HPV, which has made it possible tomodify the TNM staging system; now presenting it in two large groups, P16+ and P16-, which have different characteristics and management. In view of the heterogeneity of the disease, there are various treatments that have been used to manageit, including surgery, radiotherapy, chemotherapy and/ orimmunotherapy which will be determined taking into account the location and tumor extension. The latter treatment, is aimedat stimulating the patient's immune system in order to generate the destruction of tumor cells, are performed prior to a surgical intervention to reduce the size of the tumor. A remarkable therapy is that of blocking immune checkpoints, especially anti-PD-1 and anti-CTLA. Immunotherapy is becoming more and more prominent, however, there is still much to discover, so we believe that we should continue investigating the ways of evasion of immune reactions by cancer cells(AU)

Enfrentamiento a una masa cervical no tiroidea en Atención Primaria / Confrontation with a non-thyroid cervical mass in Primary Care

The clinical approach to non-thyroid cervical masses in primary care has always been considered a diagnostic challenge. In the absence of specific diagnostic methods, the general practitioner must rely on clinic and general tests in order to achieve a suspected diagnosis and timely referral. On initial approach to cervical masses, one must first analyze each case according to patient age, associating an exhaustive anamnesis focused on the growth pattern and aggregate symptoms, along with a physical examination focused on signs of malignancy. Once completed, the etiology of the mass can be classified as probable congenital, inflammatory or tumoral origin. And also try to determine localization, temporality and discriminate between benign and malignant causes. Once the clinical interrogation has been completed, basic complementary tests and/or directed test according to suspicion can be requested. The foregoing allows the primary care physician a proper referral to specialist and/or initiation of appropriate treatment. (AU)

Fração de câncer de cabeça e pescoço atribuível ao tabaco e ao álcool em cidades de três regiões brasileiras / Fraction of head and neck cancer attributable to tobacco and alcohol in cities of three Brazilian regions

RESUMO: Objetivo: Estimar a fração de câncer de cabeça e pescoço (CCP) atribuível ao tabaco e ao álcool em cidades das regiões Centro-Oeste, Sudeste E Sul do Brasil. Métodos: Estudo caso-controle com 1.594 casos de CCP e 1.292 controles hospitalares. A associação de CCP com tabaco e álcool foi estimada pela odds ratio e intervalos de confiança de 95% via regressão logística não condicional, ajustada por idade, sexo, escolaridade, consumo de frutas e legumes, consumo de bebidas alcoólicas (para examinar o efeito do tabaco) e tabagismo (para examinar o efeito do álcool). As proporções de CCP atribuíveis ao tabaco e ao álcool foram estimadas pelo cálculo da fração atribuível (FA). Foram realizadas estimativas separadas para Goiânia (Centro-Oeste), Rio de Janeiro e São Paulo (Sudeste) e Pelotas e Porto Alegre (Sul). Resultados: A fração de CCP atribuível ao tabagismo foi discretamente mais elevada em Goiânia (FA = 90%) em comparação às cidades do Sudeste (FA = 87%) e do Sul (FA = 86%). A fração de CCP atribuível ao consumo de bebidas alcoólicas apresentou resultados similares e mais altos nas cidades do Sudeste (FA = 78%) e Sul (FA = 77%) em comparação a Goiânia (FA = 62%). Conclusão: As frações de CCP atribuíveis ao tabagismo foram mais expressivas do que para o consumo de álcool. Embora com discretas distinções entre si, as FA para tabaco e álcool observadas nas cidades das três regiões brasileiras foram semelhantes às obtidas em estudos em outras regiões da América Latina, porém, mais altas que em outras partes do mundo.

ABSTRACT: Objectives: To estimate the fraction of head and neck cancer (HNC) attributable to tobacco and alcohol in cities in the Midwest, Southeast and South regions of Brazil. Methods: Case-control study including 1,594 cases of HNC and 1,292 hospital controls. The association of HNC with tobacco and alcohol was estimated by the odds ratio and respective 95% confidence intervals through non-conditional logistic regression, adjusted for age, sex, schooling, consumption of fruits and vegetables, alcohol drinking (to examine the tobacco effect), and tobacco smoking (to examine the alcohol effect). The proportions of HNC attributable to tobacco and alcohol were estimated through the attributable fraction (AF) calculation. Separate estimates were made for Goiânia (Midwest), Rio de Janeiro and São Paulo (Southeast) and Pelotas and Porto Alegre (South). Results: The HNC fraction attributable to smoking was slightly higher in Goiânia (AF = 90%) than in cities in the Southeast (AF = 87%) and South (AF = 86%). The HNC fraction attributable to the consumption of alcoholic beverages presented similar and higher results in the cities of Southeast (AF = 78%) and South (AF = 77%) than in Goiânia (AF = 62%). Conclusion: The HNC fractions attributable to smoking were more expressive than for alcohol consumption. Although with discrete distinctions between them, the AFs to tobacco smoking and alcohol consumption in HNC observed in the cities of these three Brazilian regions were similar to those obtained in Latin America studies, but they were higher than in other parts in the world.

Chronic Stress Improves NO- and Ca2+ Flux-Dependent Vascular Function: A Pharmacological Study / Estresse Crônico Melhora a Função Vascular Dependente de NO e Fluxo De Ca2+: Um Estudo Farmacológico

Background: Stress is associated with cardiovascular diseases. Objective: This study aimed at assessing whether chronic stress induces vascular alterations, and whether these modulations are nitric oxide (NO) and Ca2+ dependent. Methods: Wistar rats, 30 days of age, were separated into 2 groups: control (C) and Stress (St). Chronic stress consisted of immobilization for 1 hour/day, 5 days/week, 15 weeks. Systolic blood pressure was assessed. Vascular studies on aortic rings were performed. Concentration-effect curves were built for noradrenaline, in the presence of L-NAME or prazosin, acetylcholine, sodium nitroprusside and KCl. In addition, Ca2+ flux was also evaluated. Results: Chronic stress induced hypertension, decreased the vascular response to KCl and to noradrenaline, and increased the vascular response to acetylcholine. L-NAME blunted the difference observed in noradrenaline curves. Furthermore, contractile response to Ca2+ was decreased in the aorta of stressed rats. Conclusion: Our data suggest that the vascular response to chronic stress is an adaptation to its deleterious effects, such as hypertension. In addition, this adaptation is NO- and Ca2+-dependent. These data help to clarify the contribution of stress to cardiovascular abnormalities. However, further studies are necessary to better elucidate the mechanisms involved in the cardiovascular dysfunction associated with stressors. (Arq Bras Cardiol. 2014; [online].ahead print, PP.0-0) .

Fundamento: Estresse está associado com complicações cardiovasculares. Objetivos: O objetivo do presente estudo foi avaliar se o estresse crônico induz alterações vasculares, e se essas alterações são dependentes de óxido nítrico (NO) e Ca2+. Métodos: Ratos machos Wistar com 30 dias de idade foram separados em 2 grupos: controle (C) e Estresse (St). Utilizou-se estresse crônico de imobilização por 1 hora/dia, 5 dias/semana, 15 semanas. Pressão arterial sistólica foi avaliada. A função vascular foi avaliada em anéis aórticos. Curvas de concentração-efeito foram realizadas para noradrenalina, na presença de L-NAME ou prazosina, cloreto de potássio (KCl), acetilcolina e nitroprussiato de sódio. Também foi efetuado um estudo para avaliação para fluxo de Ca2+. Resultados: Estresse crônico induziu hipertensão e resposta vascular diminuída para noradrenalina e KCl e aumentada para acetilcolina. A pré-incubação com L-NAME eliminou a diferença para noradrenalina. A resposta contrátil vascular para Ca2+ foi reduzida em animais estressados. Conclusão: Nossos dados sugerem que a resposta vascular ao estresse crônico seria uma adaptação aos efeitos deletérios do estresse, incluindo a hipertensão. Além disso, esses mecanismos adaptativos dependem de liberação de NO e fluxo de Ca2+. Esses resultados ajudam a esclarecer os mecanismos envolvidos nas alterações cardiovasculares associadas ao estresse. Entretanto, mais estudos são necessários para a melhor compreensão desses mecanismos. .

A review of Indian literature for association of smokeless tobacco with malignant and premalignant diseases of head and neck region.

In India, about 60% of tobacco users use smokeless tobacco (ST) alone. Head and neck squamous cell carcinoma is one of the most common cancers in India. International Agency for Research on Cancer (IARC) monograph (Vol 89) found a significant association between ST use and oral cancer. However, only a few articles from India were included in this monograph. To overcome this lacuna, we have reviewed the articles published from India investigating the association between ST use and malignant and premalignant diseases of head and neck region. Data collection has been performed by computer-aided search of the MedLine and PubMed databases using different combinations of the key words. For malignant lesions, only cohort and case control studies were considered for review. For premalignant lesions and dental diseases other than case control studies, some cross-sectional studies have also been reviewed. Studies found a significant association between ST use and cancer of the oral cavity. The association was stronger for the buccal mucosa compared to tongue and for females compared to males. Significant association noted between cancer of the hypopharynx and oropharynx with ST use but no definitive association noted for cancer of the larynx and nasopharynx. Some dental disease and oral premalignant conditions were also associated with ST use. Indian studies suggest ST use is strongly associated with cancer of the oral cavity, oropharynx and hypopharynx.

Phonoaudiology guidance in the preoperative period in the head and neck tumors

INTRODUCTION: The habit of smoking and intake of alcoholic drinks can lead to the incidence of malignant tumors in several areas, including the head or neck. Phonoaudiology is an area of oncology that is always seeking to expand its applications in oncological head and neck cases, with intervention in pre- and post-operative periods and in different clinical fields. AIM: To evaluate and describe the impact of phonoaudiology preoperative guidance in patients, specifically smokers and alcohol drinkers, with head and neck cancer. METHODS: Series Study. Interviews were conducted by telephone with 40 individuals diagnosed with malignant head and neck tumors. Questionnaires regarding the use of tobacco and alcohol were administered before and after the phonoaudiology preoperative guidance. RESULTS: Among the 40 individuals who received phonoaudiology preoperative guidance, 26 were smokers before the orientation. Of these 26 individuals, 18 (69.24%) abandoned tobacco dependence, 4 (15.38%) did not quit smoking, and 4 (15.38%) quit smoking for a few months before resuming smoking after receiving phonoaudiology preoperative guidance. Regarding alcohol consumption, 31 individuals ingested alcohol before phonoaudiology preoperative guidance. Of these 31 individuals, 17 (54.84%) abandoned alcohol dependence, 8 (25.81%) did not abstain from alcohol consumption, and 6 (19.35%) resumed alcohol consumption after a period of abstinence after receiving phonoaudiology preoperative guidance. CONCLUSION: Phonoaudiology preoperative orientations are effective in the treatment of head and neck malignant tumors.

Câncer de cabeça e pescoço: causas, prevenção e tratamento / Head and neck cancer: causes, prevention and treatment

Câncer de cabeça e pescoço é o quinto tipo de câncer mais comum e a taxa de sobrevivência não tem mudado nos últimos anos. OBJETIVO: Determinar os fatores de risco, causas, tratamento e prevenção do câncer de cabeça e pescoço. MÉTODO: Nós detalhamos os fatores de risco, causas, tratamento e prevenção da doença por meio de pesquisa nos bancos de dados PUBMED, MEDLINE e SciELO. RESULTADOS: Álcool e fumo ainda são os principais fatores de risco. Outros fatores podem influenciar o desenvolvimento do carcinoma de cabeça e pescoço. A opção de tratamento principal é terapia cirúrgica e sua utilização seguida por radioterapia é uma prática comum de tratamento em fases iniciais da doença. Existem terapias que visam agir em componentes moleculares genéticos específicos para o desenvolvimento do tumor. A cessação do cigarro, limitação de ingestão de álcool, evitar a exposição à fumaça do cigarro, a carcinogênicos ambientais, detecção precoce de infecção por HPV, manutenção da saúde bucal, bons hábitos alimentares e controle do stress podem ser medidas de prevenção da doença. CONCLUSÃO: Investigações adicionais são necessárias para completa compreensão do desenvolvimento do carcinoma de cabeça e pescoço e isso irá fornecer novos caminhos e melhora na intervenção e abordagens terapêuticas.

Although head and neck carcinoma ranks fifth among cancer types, patient survival rates have not changed significantly over the past years. OBJECTIVE: To determine the risk factors, causes, therapies, and prevention measures for head and neck cancer. METHOD: Risk factors, causes, therapies, and preventive measures for this disease were searched on databases PUBMED, MEDLINE, and SCIELO. RESULTS: Alcohol and tobacco are still atop risk factors. Other factors may influence the development of head and neck carcinoma. Surgery is the main treatment option, and the addition of radiotherapy following surgery is frequent for patients in the early stages of the disease. Other therapies target specific genetic molecular components connected to tumor development. Disease preventive measures include smoking cessation, limiting alcohol intake, preventing exposure to tobacco smoke and environmental carcinogenic agents, early detection of infection by HPV, maintaining oral health, good eating habits, and managing stress. CONCLUSION: Additional research is needed for a more thorough understanding of the development of head and neck carcinomas and to shed light on new ways to improve therapeutic approaches and interventions.

Avaliação do efeito do Papilomavírus Humano (HPV) no risco do câncer de cabeça e pescoço / Effect evaluation of human papillomavirus (HPV) on the risk of head and neck cancer

A associação do HPV ao câncer de orofaringe tem sido sugerida, apesar da varißvel prevalência viral nos diferentes estudos. Por outro lado, a relação etiológica do HPV em casos de câncer oral ou de hipofaringe/laringe é ainda controversa. No entanto, estudos recentes tem sugerido que a presença do DNA do HPV nos tumores não é evidência suficiente para a associação causal, sendo fortemente indicado anßlises de expressão das oncoproteínas virais e do status do genoma do HPV. N presente estudo caso-controle, a prevalência do HPV foi analisada utilizando PCR-nested para detecção viral em 228 casos de câncer de cabeça e pescoço e 227 controles. A anßlise multivariada dos diferentes tipos de HPV e outros fatores de risco epidemiológicos, ambientais, clínicos e moleculares suportou a associação etológica do HPV no câncer de orofaringe corroborando a hipótese de duas diferentes vias na carcinogênese, uma desencadeada por fatores ambientais, como o consumo de tabaco e ßlcool e outra direcionada pelo HPV, cujo efeito é evidenciado na ausência desses outros fatores de risco. Entretanto , os dados aqui apresentados sugerem uma relação limitada do HPV aos tumores da cavidade oral e hipofaringe/laringeApesar da similaridade da prevalência do HPV em casos e controles, os dados deste estudo sugerem fortemente que a distribuição dos tipos de HPV quanto ao potencial carcinogênico é diferenciado, sendo HPV de baixo risco mais frequente em controles e de alto-risco nos casos de câncer de orofaringe...

O estudo de casos para presença de DNA e transcritos de RNA de E6 e E7 do HPV por ISH em dois TMAs construídos para o presente estudo mostrou atividade transcricional apenas para os casos de câncer de orofaringe. A superexpressão de p16INK4a foi coincidente na identificação de atividade do HPV por IHQ em caso de câncer de orofaringe, mostrando a eficiência deste marcadorA presença de DNA do HPV integrado ao genoma foi detectada na maioria dos casos de câncer de orofaringe, diferente do encontrado para casos de câncer da cavidade oral ou hipofaringe/laringe. Este cenßrio mostra claramente a distinta associação etiológica do HPV nos diferentes sítios anatômicos de câncer de cabeça e pescoço, principalmente nos pacientes com câncer de orofaringe sem exposição aos principais fatores de risco, o tabaco e ßlcool...

Head and neck squamous cell carcinoma: decline in clinical stage at the time of diagnosis in a reference hospital in southern Brazil

Objective: Developing countries have a high incidence of head and neck squamous cell carcinoma (HNSCC). Risk factors are smoking and alcohol consumption; socioeconomic status and oral health may be associated with etiology. The aim of this study was to evaluate the sociodemographicprofile and oral health of patients with primary HNSCC, as well as the clinical and histopathological characteristics of the tumor. Material and Methods: We evaluated 78 patients; data about sex, age, skin color, schooling, oral hygiene, smoking, alcohol consumption and socioeconomic status were collected using a structured questionnaire. An intraoral examination provided dataabout caries, missing teeth and dental prosthesis. Hospital records were reviewed to collect clinical tumor information. Results: Mean age was 57.6 years; most participants were male,white, former or current smokers and moderate or high consumption of alcoholic beverages with low socioeconomic and educational levels. The majority of patients were disease-free at 2 year-follow up. Classification showed 60.2% of the tumors as T1 and T2 and 59% had no regional involvement. Most tumors were found in the mouth, and the tongue was the most frequent site. Histopathological examination revealed that 57.7% of the tumors were classified as moderateand poor prognosis. Conclusion: The profile of patients with HNSCC was similar to that found in other populations, but there is a decline in clinical stage at the time of diagnosis, and detecting this tumor at an early stage can be an effective mean to determine a better prognosis for patients

Education, tobacco smoking, alcohol consumption, and IL-2 and IL-6 gene polymorphisms in the survival of head and neck cancer

The association of education, tobacco smoking, alcohol consumption, and interleukin-2 (IL-2 +114 and -384) and -6 (IL-6 -174) DNA polymorphisms with head and neck squamous cell carcinoma (HNSCC) was investigated in a cohort study of 445 subjects. IL-2 and IL-6 genotypes were determined by real-time PCR. Cox regression was used to estimate hazard ratios (HR) and 95 percent confidence intervals (95 percentCI) of disease-specific survival according to anatomical sites of the head and neck. Mean age was 56 years and most patients were males (87.6 percent). Subjects with 5 or more years of schooling had better survival in larynx cancer. Smoking had no effect on HNSCC survival, but alcohol consumption had a statistically significant effect on larynx cancer. IL-2 gene +114 G/T (HR = 0.52; 95 percentCI = 0.15-1.81) and T/T (HR = 0.22; 95 percentCI = 0.02-3.19) genotypes were associated with better survival in hypopharynx cancer. IL-2 +114 G/T was a predictor of poor survival in oral cavity/oropharynx cancer and larynx cancer (HR = 1.32; 95 percentCI = 0.61-2.85). IL-2 -384 G/T was associated with better survival in oral cavity/oropharynx cancer (HR = 0.80; 95 percentCI = 0.45-1.42) and hypopharynx cancer (HR = 0.68; 95 percentCI = 0.21-2.20), but an inverse relationship was observed for larynx cancer. IL-6 -174 G/C was associated with better survival in hypopharynx cancer (HR = 0.68; 95 percentCI = 0.26-1.78) and larynx cancer (HR = 0.93; 95 percentCI = 0.42-2.07), and C/C reduced mortality in larynx cancer. In general, our results are similar to previous reports on the value of education, smoking, alcohol consumption, and IL-2 and IL-6 genetic polymorphisms for the prognosis of HNSCC, but the risks due to these variables are small and estimates imprecise.

Manutenção do tabagismo e etilismo em pacientes tratados por câncer de cabeça e pescoço: influência do tipo de tratamento oncológico empregado / Tobacco and alcohol use after head and neck cancer treatment: influence of the type of oncological treatment employed

OBJETIVO: Avaliar a taxa de manutenção do tabagismo e etilismo em pacientes tratados por carcinoma epidermoide da cabeça e pescoço e comparar o resultado observado com a modalidade do tratamento oncológico empregado. MÉTODOS: Foram incluídos 110 pacientes tratados por carcinoma epidermoide das vias aereodigestivas altas, divididos em grupo cirúrgico, tratado com cirurgia, e grupo clínico, tratado com quimioterapia e/ou radioterapia. Os pacientes foram entrevistados a fim de determinar se houve manutenção dos hábitos após o tratamento. Comparou-se a taxa de manutenção dos hábitos com a modalidade de tratamento empregada. Testou-se também a relação entre o status oncológico dos pacientes com as taxas de tabagismo e etilismo encontradas. RESULTADOS: Entre os tabagistas, 35 por cento mantiveram este hábito após o tratamento. No grupo clínico, houve um percentual significativamente maior de pacientes que mantiveram o tabagismo com relação ao grupo cirúrgico (58,3 por cento x 25 por cento; p = 0,004). Entre os etilistas, 16,6 por cento continuaram a ingerir bebidas alcoólicas, percentagem que também se mostrou maior no grupo clínico (23,8 por cento x 13,3 por cento), porém sem diferença estatisticamente significativa. O status oncológico dos pacientes não apresentou relação com a manutenção dos hábitos estudados. CONCLUSÃO: São altas as taxas de manutenção de tabagismo e etilismo após o tratamento do carcinoma epidermoide de cabeça e pescoço, especialmente se considerarmos o tabagismo nos pacientes tratados com quimioterapia e/ou radioterapia. Uma abordagem multidisciplinar mais efetiva é necessária com vista a obter melhores taxas de abandono do tabaco e do álcool, especialmente no grupo de pacientes submetidos a tratamentos não cirúrgicos.

OBJECTIVE: To assess the cigarette smoking and alcohol intake maintenance rate in patients treated for head and neck squamous cell carcinoma and to compare the observed outcome with the type of oncological treatment employed. METHODS: One hundred and ten patients treated for high aero-digestive tract squamous cell carcinoma were included and divided into a surgical group, treated with a surgery, and a medical group, treated with chemotherapy and/or radiation. The patients were interviewed to determine whether or not they had persisted with the smoking and drinking behavior after treatment. The habit maintenance rate was compared with the treatment modality employed. The relationship between the oncological status of the patients and the cigarette smoking and alcohol intake rates found was also tested. RESULTS: Among smokers, 35 percent maintained the habit after treatment. The medical group had a significantly higher percentage of patients maintaining smoking compared with the surgical group (58.3 percent vs 25.0 percent; p = 0.004). Among alcohol users, 16.6 percent kept drinking alcoholic beverages, with a percentage also shown higher for the medical group (23.8 percent vs 13,3 percent), but with no statistically significant difference. The oncological status of patients was not related to the maintenance of the habits studied. CONCLUSION: Smoking and alcoholism maintenance rates are high after head and neck squamous cell carcinoma is treated, especially if we consider smoking in patients treated with chemotherapy and/or radiation. A more effective multidisciplinary approach is required in order to obtain better rates of tobacco and alcohol quitting, especially in patients undergoing non-surgical treatments.

Polimorfismo do gene metilenotetra-hidrofolato redutase (MTHFR) e o risco de carcinoma espinocelular de cabeça e pescoço / Polymorphism of methylenetetrahydrofolate reductase (MTHFR) gene and risk of head and neck squamous cell carcinoma

O polimorfismo C677T do gene metilenotetra-hidrofolato redutase (MTHFR) pode ser um fator de risco para o carcinoma espinocelular de cabeça e pescoço devido a alterações nos níveis de folato que podem induzir alterações na metilação intracelular, promovendo a carcinogênese. OBJETIVO: Avaliar o polimorfismo MTHFR C677T em pacientes com carcinoma espinocelular de cabeça e pescoço e em indivíduos sem história de neoplasia e verificar a associação desta doença com as características clínico-patológicas. CASUÍSTICA E MÉTODOS: Estudo retrospectivo no qual foram avaliados gênero, idade, tabagismo, etilismo e parâmetros clínico-histopatológicos em 200 indivíduos (100 com a doença e 100 sem história de neoplasia). A análise molecular foi realizada pela técnica de PCR- RFLP e os testes qui-quadrado de Pearson e Regressão Logística Múltipla foram utilizados para análise estatística. RESULTADOS: Não houve associação entre o polimorfismo MTHFR C677T e a doença (p=0,50). Diferenças significantes entre o grupo de pacientes e o grupo controle foram observadas para idade superior a 50 anos, hábito tabagista e gênero masculino (p<0,001). Não houve associação da doença com os parâmetros clínico-histopatológicos. CONCLUSÃO: Não foi possível estabelecer uma associação entre o polimorfismo MTHFR C677T e o carcinoma espinocelular de cabeça e pescoço.

Methylenetetrahydrofolate reductase gene (MTHFR) C677T polymorphism may be a risk factor for head and neck squamous cell carcinoma due to changes in folate levels that can induce disorders in the methylation pathway, which results in carcinogenesis. AIM: To evaluate MTHFR C677T polymorphism in patients with head and neck squamous cell carcinoma and in individuals with no history of cancer, and to assess the association of this disease with clinical histopathological parameters. SERIES AND METHODS: A retrospective study that assessed gender, age, tobacco, alcohol consumption and clinical histopathological parameters in 200 patients (100 with disease and 100 with no history of cancer). PCR-RFLP molecular analysis was carried out and the chi-square test and multiple logistic regression were applied for the statistical analysis. RESULTS: There was no association between MTHFR C677T polymorphism and head and neck cancer (p = 0.50). Significant differences between the study and control groups were observed at age over 50 years, tobacco use, and male gender (p <0.001). There was no association of disease with clinical-histopathological parameters. CONCLUSION: No association between the MTHFR C677T polymorphism and head and neck squamous cell carcinoma was possible in this study.

Manejo clínico do carcinoma de cabeça e pescoço / Clinical management of head and neck cancer

Justificativa e objetivos: Segundo estimativas do Instituto Nacional do Câncer (INCA), 14.120 novos casos de neoplasias de cavidade oral são esperados para 2010 no Brasil, sendo destes, 10.330 casos em pacientes masculinos, estando entre as mais altas taxas do mundo. O objetivo deste trabalho é realizar uma revisão da literatura, no intuito de sintetizar as informações sobre este relevante problema de saúde pública no Brasil. Conteúdo: Um resumo da literatura sobre carcinoma espinocelular de cabeça e pescoço (CECCP) desde o diagnóstico até o tratamento da doença localizada e recidivada/metastática, contendo etiologia, patogênese, diagnóstico, estadiamento e tratamento, com ênfase em: quimioterapia de indução, terapia de resgate e terapia paliativa. Enfocamos nas situações mais relevantes de nosso meio, em que a grande maioria dos pacientes é admitida nos Serviços com doença avançada. Conclusão: Atualmente CECCP é uma doença com prognóstico reservado e novos avanços são necessários para o melhor manejo desses pacientes.

Masas cervicales / Cervical masses

La región cervical es asiento de numerosas lesiones debido a su riqueza anatómica. En una pequeña área, se hallan presentes varios sistemas: digestivo, respiratorio, vascular, nervioso, ganglionar, glandular. Teniendo como reparo los diferentes espacios anatómicos, desarrollaremos en esta revisión la patología cervical más frecuente y sus características en los diferentes métodos de diagnóstico.

Polimorfismos GSTT1 e GSTM1 em indivíduos tabagistas com carcinoma espinocelular de cabeça e pescoço / GSTT1 and GSTM1 polymorphism in cigarette smokers with head and neck squamous cell carcinoma

A variabilidade em genes relacionados aos processos de ativação e detoxificação de carcinógenos pode interferir na suscetibilidade ao câncer. OBJETIVO: Investigar a relação entre os polimorfismos GSTT1 e GSTM1 nulos e o risco para o carcinoma espinocelular de cabeça e pescoço em indivíduos tabagistas. MATERIAL E MÉTODO: Este estudo caso-controle foi realizado na Faculdade de Medicina de São José do Rio Preto, Brasil. Foram avaliadas as freqüências dos genótipos nulos GSTT1 e GSTM1 por PCR multiplex em 60 pacientes com carcinoma espinocelular de cabeça e pescoço e 60 indivíduos sem a doença. RESULTADOS: A cavidade oral foi o sítio de tumor mais freqüente. O genótipo GSTT1 nulo foi encontrado em 33,3 por cento dos pacientes e em 23,3 por cento dos indivíduos controles (p=0,311). Os grupos caso e controle apresentaram freqüências do genótipo GSTM1 nulo de 35 por cento e 48,3 por cento, respectivamente (p=0,582). Não foram encontradas associações entre o hábito etilista e genótipos nulos GSTT1 e GSTM1 em ambos os grupos (valores de p>0,05). O gênero masculino e o hábito etilista foram prevalentes em ambos os grupos. CONCLUSÃO: Neste estudo não foi possível estabelecer uma correlação entre os genótipos nulos GSTT1 e GSTM1 e o carcinoma espinocelular de cabeça e pescoço em indivíduos tabagistas.

Gene variability related to carcinogen activation and detoxification may interfere with susceptibility to head and neck cancer. AIM: To investigate the relation between GSTT1 and GSTM1 null polymorphisms and the risk of head and neck squamous cell carcinoma in cigarette smokers. MATERIAL AND METHOD: A case-control study conducted at the Sao Jose do Rio Preto Medical School, Brazil. GSTM1 and GSTT1 null genotype frequencies were evaluated by multiplex PCR in 45 cigarette smokers with head and neck squamous cell carcinomas and 45 cigarette smokers without this disease. RESULTS: The oral cavity was the most prevalent tumor site for squamous cell carcinoma. The GSTT1 null genotype was found in 33.3 percent of the Experimental Group and 23.3 percent of the Control Group (p= 0.311). Experimental and Control Groups had GSTM1 null genotype frequencies of 35 percent and 48.3 percent (p=0.582). No association between alcohol consumption and GSTT1 and GSTMI null genotypes was found in these groups (p-values>0.05). There were more men, and alcohol consumption was prevalent in both groups. CONCLUSION: In this study we were unable to show a correlation between GSTM1 and GSTT1 genotypes and the development of head and neck squamous cell carcinomas in cigarette smokers.

El cáncer de cabeza y cuello: factores de riesgo y prevención / Head and neck cancer: risk factors and prevention

La frecuencia del carcinoma epidermoide originado en mucosas de cabeza y cuello ha aumentado mundialmente en la última década, sobre todo en países con economías emergentes; el cáncer de cavidad oral ocupa el sexto lugar de todas las neoplasias. Aquí se lleva a cabo una revisión de la literatura en relación a la epidemiología y factores de riesgo en cáncer de cabeza y cuello, y se hace énfasis en la prevención del carcinoma originado en mucosas de vías aerodigestivas superiores. Se concluye que el pronóstico de los pacientes con cáncer de cabeza y cuello depende de la etapa clínica, y si bien la identificación de población en riesgo y de lesiones precursoras, así como el diagnóstico precoz disminuyen la tasa de mortalidad, el esfuerzo mayor debe hacerse en la prevención primaria.

The frequency of squamous cell carcinoma originating in head and neck mucosae has increased worldwide in the last decade, particularly in countries with emerging economies; oral cavity cancer is ranked in 6th place for all neoplasias. We conducted a literature review related to epidemiology and risk factors in head and neck cancer in order to analyze the most significant etiological factors and to emphasize prevention of carcinoma originating in head and neck mucosae. The prognosis in head and neck cancer patients depends on the clinical stage at time of diagnosis; therefore, identification of high-risk populations, precancerous lesions and early diagnosis decrease mortality. Nevertheless, the major effort must be on primary prevention.

Tratamiento concomitante con gemcitabina y radioterapia en pacientes con carcinoma epidermoide locorregionalmente avanzado de cabeza y cuello: estudio fase II / Concomitant treatment with gemcitabine and radiotherapy in patients with advanced stages of epidermoid carcinoma originating in the head and neck: a phase II sutdy

Antecedentes: En casos avanzados el tratamiento clásico del carcinoma epidermoide originado en mucosas de cabeza y cuello es cirugíaradioterapia o radioterapia sola (RTS). Sin embargo los resultados en carcinoma localmente avanzado (CLA) son decepcionantes. La asociación quimioterapia-radioterapia (QT-RT) ha demostrado ser superior a RTS en enfermedad irresecable y, en enfermedad resecable podría sustituir a la cirugía inicial y dejarla como rescate. Objetivo: El objetivo de este estudio es conocer la tasa de respuesta y la toxicidad del tratamiento concomitante Gemcitabina-Radioterapia (GRT) en pacientes con CLA. Material y métodos: Estudio prospectivo en el que pacientes con CLA recibieron GRT concomitante; se evaluó la tasa de respuesta global, completa, parcial y la toxicidad. Se incluyeron 15 pacientes, 5 mujeres y 10 hombres, 73% en etapa IVa. Resultados: Trece de 15 pacientes tuvieron respuesta global (87%), en 9(60%) fue completa (RC) y 2 tuvieron progresión. Todos tuvieron toxicidad, la más frecuente fue mucositis grado 4 en 46%; de éstos 40% requirió apoyo nutricio por sonda o gastrostomía. Un paciente en RC murió por sepsis. Ninguno abandonó el tratamiento. Conclusiones: La asociación GRT ofrece tasa de respuesta completa en 60%; sin embargo, la morbilidad no es despreciable; se requieren estudios aleatorizados con mayor número de pacientes que permitan definir el mejor esquema terapéutico.

BACKGROUND: Surgery, radiotherapy or radiotherapy alone (RTA) constitute conventional treatment regimes for advanced stages of squamous cell carcinoma originating in the head and neck mucosa. Nevertheless, the results in advanced regional carcinoma (ARC) are disappointing. The chemotherapy-radiotherapy (CHT-RT) association has shown to be superior to RTA in irresectable disease and in resectable disease it could substitute initial surgery as a rescue alternative. OBJECTIVE: Our objective is to report the response rate and toxicity of concurrent treatment with Gemcitabine and Radiotherapy (GRT) in patients with ARC. In a prospective design, patients with ARC received concurrent GRT; the global, complete and partial response rate as well as toxicity were assessed. MATERIAL AND METHODS: 15 patients were included, 5 women and 10 men, 73% in stage IVa; 13/15 showed a global response (87%), a complete response was observed in 9 cases (60%) (RC) and 2 showed progress. RESULTS: All patients included showed toxicity, the most frequent one was level 4 mucositis in 46%, of this 40% required nutritional support by catheter or gastrostomy. One patient in RC died due to sepsis. None of them suspended treatment. CONCLUSION: The GRT association offers a complete response rate of 60%; nevertheless morbidity was not insignificant; randomized studies with a larger number of patients will be required to allow us to outline the optimal therapeutic scheme.