Prognostic markers in head and neck carcinoma

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide. Well-known risk factors include tobacco smoking and alcohol consumption. Overall survival has improved, but is still low especially in developing countries. One reason for this is the often advanced stage of the disease at the time of diagnosis, but also lack of reliable prognostic tools to enable individualized patient treatment to improve outcome. To date, the TNM classification still serves as the best disease evaluation criterion, although it does not take into account the molecular basis of the tumor. The need for surrogate molecular markers for more accurate disease prediction has increased research interests in this field. We investigated the prevalence, physical status, and viral load of human papillomavirus (HPV) in HNSCC to determine the impact of HPV on head and neck carcinogenesis. The prevalence and genotyping of HPV were assessed with an SPF10 PCR microtiter plate-based hybridization assay (DEIA), followed by a line probe-based genotyping assay. More than half of the patients had HPV DNA in their tumor specimens. Oncogenic HPV-16 was the most common type, and coinfections with other oncogenic and benign associated types also existed. HPV-16 viral load was unevenly distributed among different tumor sites; the tonsils harbored significantly greater amounts of virus than other sites. Episomal location of HPV-16 was associated with large tumors, and both integrated and mixed forms of viral DNA were detected. In this series, we could not show that the presence of HPV DNA correlated with survival. In addition, we investigated the prevalence and genotype of HPV in laryngeal carcinoma patients in a prospective Nordic multicenter study based on fresh-frozen laryngeal tumor samples to determine whether the tumors were HPV-associated. These patients were also examined and interviewed at diagnosis for known risk factors, such as tobacco smoking and alcohol consumption, and for several other habituations to elucidate their effects on patient survival. HPV analysis was performed with the same protocols as in the first study. Only 4% of the specimens harbored HPV DNA. Heavy drinking was associated with poor survival. Heavy drinking patients were also younger than nonheavy drinkers and had a more advanced stage of disease at diagnosis. Heavy drinkers had worse oral hygiene than nonheavy drinkers; however, poor oral hygiene did not have prognostic significance. History of chronic laryngitis, gastroesophageal reflux disease, and orogenital sex contacts were rare in this series. To clarify why vocal cord carcinomas seldom metastasize, we determined tumor lymph vessel (LVD) and blood vessel (BVD) densities in HNSCC patients. We used a novel lymphatic vessel endothelial marker (LYVE-1 antibody) to locate the lymphatic vessels in HNSCC samples and CD31 to detect the blood microvessels. We found carcinomas of the vocal cords to harbor less lymphatic and blood microvessels than carcinomas arising from sites other than vocal cords. The lymphatic and blood microvessel densities did not correlate with tumor size. High BVD was strongly correlated with high LVD. Neither BVD nor LVD showed any association with survival in our series. The immune system plays an important role in tumorigenesis, as neoplastic cells have to escape the cytotoxic lymphocytes in order to survive. Several candidate HLA class II alleles have been reported to be prognostic in cervical carcinomas, an epithelial malignancy resembling HNSCC. These alleles may have an impact on head and neck carcinomas as well. We determined HLA-DRB1* and -DQB1* alleles in HNSCC patients. Healthy organ donors served as controls. The Inno-LiPA reverse dot-blot kit was used to identify alleles in patient samples. No single haplotype was found to be predictive of either the risk for head and neck cancer, or the clinical course of the disease. However, alleles observed to be prognostic in cervical carcinomas showed a similar tendency in our series. DRB1*03 was associated with node-negative disease at diagnosis. DRB1*08 and DRB1*13 were associated with early-stage disease; DRB1*04 had a lower risk for tumor relapse; and DQB1*03 and DQB1*0502 were more frequent in controls than in patients. However, these associations reached only borderline significance in our HNSCC patients.

Laryngeal and voice disorders in patients with gastroesophageal symptoms. Correlation with pH-monitoring

OBJETIVO: Investigar as alterações laríngeas e vocais em pacientes com sintomas de refluxo gastroesofágico e correlacioná-las com o exame de phmetria. MÉTODOS: Estudo prospectivo que incluiu os pacientes atendidos nos ambulatórios de Distúrbios da Voz da Faculdade de Medicina de Botucatu no período de cinco anos com sintomas vocais e gastroesofágicos. Os pacientes foram submetidos à videolaringoscopia, às análises vocais perceptivo-auditivas, a analise vocal acústica computadorizada e ao exame de pHmetria de dois canais com monitorização durante 24 horas. RESULTADOS: Foram incluídos 57 pacientes (entre 21 a 65 anos; 45 mulheres e 12 homens). Desses, 18 apresentavam pHmetria normal (31,6%) e 39 alterada (68,4%). As videolaringoscopias registraram diversas lesões laríngeas tanto nos pacientes com pHmetria normal como alterada, sendo mais relevantes neste último grupo, destacando-se a paquidermia posterior. As avaliações vocais perceptivo-auditivas identificaram alterações vocais de diversas intensidades em ambos os grupos, mais importantes nos pacientes com pHmetria alterada. Todos os parâmetros acústicos, exceto Fo, mostraram-se alterados em ambos os grupos, quando comparados aos controles. CONCLUSÕES: Alterações vocais perceptivas e acústicas, e lesões laríngeas foram registradas tanto nos pacientes com phmetria normal como alterada, sinalizando para a importância da historia clínica e dos achados videolaringoscópicos no diagnóstico das laringites ácidas.

Tosse, uma visão do otorrinolaringologista.

Persistent cough leads individuals to seek for medical assistance. Clinical investigation, however, may not reveal any alteration within the clinic's sphere of action. Often enough, some professionals treat the symptom as a disease, introducing several medicines, unsuccessfully. The author's experience, as an otolaryngologist, allows to state that many of these professionals ignore the upper aerodigestive tract as a cough-generator site. The present work discusses the alterations on the mentioned tract, which may provoke the cough reflex, reviewing, initially, the cough mechanism and the localization of the specific receptors. Cough is produce by stimulus at the receptor level or far from it. In upper and lower parts of the aerodigestive tract secretions may run to several directions. Secretion from the paranasal sinus is a frequent cause of cough. Acute sinusitis may occur insidiously bringing about the chronification of the inflammation with cough being the only great apparent symptom. Nasal and dental alterations favor sinusal infection. Signs and symptoms, even if minimum, may be detected through an accurate anamnesis. Nasal allergy, laryngitis, post nasal dripping and septal deviation may also produce cough. The ORL examination is, therefore, imperative, and no radiologic examination can substitute for it. An inadequate treatment, particularly of the sinusitis, may bring about a worsening and extension of the initial condition.

Eficácia e segurança do uso inalatório da adrenalina-L na laringite pós-intubação utilizada em associação com a dexametasona

Objective: to assess the efficacy and safety of the use of nebulized L-epinephrine associated with dexamethasone in post-intubation laryngitis. Method: we carried out a prospective, randomized, double-blind, placebo controlled study with two cohorts of patients with postintubation laryngitis graded 3 to 6 by Downes and Raphaely score and during two years. Our population was divided into two groups: A and B; both groups received intravenous dexamethasone and nebulized saline with (group B) and without (group A) L-epinephrine. The efficacy was assessed by Downes and Raphaely's score. The side effects of epinephrine were evaluated according to occurrence of arrhythmia, to increased blood pressure, and to average heart rate of group B in comparison to group A. Results: twenty-two patients were included in group A (average score = 4.8) and 19 in group B (average score = 5.2). During treatment, 3 patients in group A presented a score of 8 and were reintubated. This group also showed higher clinical scores than group B during the first two hours of the protocol; these results were not statistically significant. No side effects were observed due to epinephrine. The gasometric parameters were adequate in both groups, but better in the control group. Conclusions: we did not observe increased efficacy for the treatment of post-intubation laryngitis when nebulized L-epinephrine was used simultaneously with intravenous dexamethasone. Some indicators, however, did present a favorable trend when combined therapy was used and should be submitted to further evaluation.

Influencia da obesidade na correlacao entre refluxo faringolaringeo e apneia obstrutiva do sono

Introdução:A apneia obstrutiva do sono (AOS) é causada por episódios recorrentes de obstrução total ou parcial da via aérea superior com duração superior a 10 segundos durante o sono. Refluxo faringolaríngeo (RFL) é uma variante da doença do refluxo gastroesofágico que afeta a laringe e a faringe.Objetivos:Avaliar a influência da obesidade na relação entre RFL e AOS em pacientes com SAOS.Materiais e métodos:Estudo observacional transversal retrospectivo. Foram revisados protocolos de atendimento de pacientes com AOS que incluem questionários validados para RFL como Reflux Sympton Index (RSI) e Reflux Finding Score (RSI), nasolaringofibroscopia e polissonografia.Resultados:Cento e cinco pacientes foram divididos em grupo de obesos (39 pacientes) e não obesos (66 pacientes). Na avaliação das médias do RSI o grupo de não obesos foi semelhante entre pacientes com AOS leve (11,96) e moderada (11,43). No grupo de obesos a média do RSI foi de 6,7 em pacientes com AOS leve e de 11,53 em pacientes com AOS moderada a grave (p < 0,05).Discussão:O subgrupo de pacientes com AOS e RFL apresenta vários fatores que promovem a inflamação da via aérea superior. Pacientes com AOS devem ser pesquisados e tratados quanto a RFL, aumentando a qualidade de vida.Conclusão:O RFL e a AOS se correlacionam positivamente em pacientes obesos.

Avaliação clínica, videolaringoscópica e vocal perceptivo-auditiva e acústica de professores disfônicos

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Prevalence of vocal problems in portuguese primary and secondary shool level teachers

This study compared the prevalence of vocal problems in two Portuguese groups: 73 teachers that use their voice as professional tool (teachers’ group) and 73 non-voice professionals (control group). It also identified the risk factors that contributed to teachers’ group voice problems. A questionnaire was applied to both goups in order to obtain information about vocal health, hygiene and behavior, professional activity and general physical health. Statistical results revealed that the teachers’ group presented a higher prevalence of vocal problems than the control group: 52% reported hoarseness, 46.6% vocal fatigue and 45.2% vocal discomfort compared with 31.5%, 20.5 % e 28.7%, respectively. Environmental factors (eg., smoke and cold temperatures), vocal abuse and upper respiratory pathologies (e.g., colds, laryngitis and pharyngitis) seemed to increase teachers’ voice disorders (p-value < .05). In conclusion, the absence of vocal pedagogy in the curricular plan of teachers’ higher education associated to poor working environmental conditions and professional voice demands explained the higher prevalence of vocal problems in teachers’ group.