Supratracheal laryngectomy: a multi-institutional study / Laringectomia supratraqueal: um estudo multi-institucional

Abstract Introduction: Supratracheal laryngectomy has been described as a surgical procedure for glottic or supraglottic cancer extending to the subglottic region and/or involving the cricoarytenoid joint, aiming to preserve laryngeal function (breathing, phonation and swallowing), without diminishing locoregional cancer control. The choice of supracricoid laryngectomy in these cases could result in a high risk of compromised resection margins. Objective: To determine the safety, viability, adequacy of surgical margins and the supratracheal laryngectomy results for intermediate and advanced laryngeal cancer by reviewing the results at three different institutions in Brazil. Methods: This is a retrospective study that analyzed the charts of 29 patients submitted to supratracheal laryngectomy from October 1997 to June 2017. The type of laryngectomy performed was classified according to the European Laryngological Society classification for horizontal laryngectomies. Early and late results were evaluated. Survival rates (overall, specific, disease-free and total laryngectomy-free survival) were calculated. The mean follow-up time was 44 months. Results: Of the 29 patients submitted to supratracheal laryngectomy, 25 had no previous treatment. One patient (3.4%) had compromised margins. Four patients (13.8%) had recurrence. Of these, three had local recurrence and one had regional recurrence. Five patients (17.2%) required a total laryngectomy, two due to ruptured pexy and three due to local recurrence. Four of these patients (80%) achieved a successful total procedure. Four patients (13.8%) died, two due to postoperative complications and two due to recurrence. Overall, specific, disease-free and total laryngectomy-free survival at 5 years were, respectively, 82.1%; 88.2%; 83.0% and 80.2%. Conclusion: Selected patients with intermediate and advanced laryngeal cancer may benefit from supratracheal laryngectomy, that resulted in total laryngectomy-free survival and specific survival of 80.2% and 88.2%, respectively.

Resumo Introdução: A laringectomia supratraqueal tem sido descrita como um procedimento cirúrgico com objetivo de preservar a função da laringe (respiração, fonação e deglutição), sem prejuízo no controle oncológico locorregional, para câncer glótico ou supraglótico com extensão à subglote e/ou envolvimento da articulação cricoaritenóidea. A opção pela laringectomia supracricoide nesses casos poderia resultar em grande risco para margens de ressecção comprometidas. Objetivo: Determinar a segurança, viabilidade, adequação das margens cirúrgicas e os resultados da laringectomia supratraqueal para o câncer de laringe intermediário e avançado através da revisão dos resultados de três instituições distintas no Brasil. Método: Estudo retrospectivo, com análise dos prontuários de 29 pacientes submetidos à laringectomia supratraqueal, de outubro de 1997 a junho de 2017. O tipo de laringectomia realizada foi classificado de acordo com a classificação da Sociedade Laringológica Europeia para laringectomias horizontais. Foram avaliados os resultados precoces e tardios. As taxas de sobrevida (global, específica, livre de doença e livre de laringectomia total) foram calculadas. O tempo médio de seguimento foi 44 meses. Resultados: Dos 29 pacientes submetidos à laringectomia supratraqueal, 25 não tinham tratamento prévio. Um paciente (3,4%) teve margens comprometidas. Quatro pacientes (13,8%) recidivaram. Desses, três tiveram recidiva local e um apresentou recidiva regional. Cinco pacientes (17,2%) necessitaram de totalização da laringectomia, duas por ruptura da pexia e três por recidiva local. Quatro desses pacientes (80%) obtiveram sucesso na totalização. Quatro pacientes (13,8%) foram a óbito, dois por complicações pós-cirúrgicas e dois por recidiva. As sobrevidas global, específica, livre de doença e livre de laringectomia total em 5 anos foram, respectivamente, 82,1%; 88,2%; 83,0% e 80,2%. Conclusão: Pacientes selecionados com câncer intermediário e avançado de laringe podem ser beneficiados com laringectomia supratraqueal, que ofereceu sobrevida livre de laringectomia total e sobrevida específica de 80,2% e 88,2%, respectivamente.

Supratracheal laryngectomy: a multi-institutional study.

INTRODUCTION: Supratracheal laryngectomy has been described as a surgical procedure for glottic or supraglottic cancer extending to the subglottic region and/or involving the cricoarytenoid joint, aiming to preserve laryngeal function (breathing, phonation and swallowing), without diminishing locoregional cancer control. The choice of supracricoid laryngectomy in these cases could result in a high risk of compromised resection margins. OBJECTIVE: To determine the safety, viability, adequacy of surgical margins and the supratracheal laryngectomy results for intermediate and advanced laryngeal cancer by reviewing the results at three different institutions in Brazil. METHODS: This is a retrospective study that analyzed the charts of 29 patients submitted to supratracheal laryngectomy from October 1997 to June 2017. The type of laryngectomy performed was classified according to the European Laryngological Society classification for horizontal laryngectomies. Early and late results were evaluated. Survival rates (overall, specific, disease-free and total laryngectomy-free survival) were calculated. The mean follow-up time was 44 months. RESULTS: Of the 29 patients submitted to supratracheal laryngectomy, 25 had no previous treatment. One patient (3.4%) had compromised margins. Four patients (13.8%) had recurrence. Of these, three had local recurrence and one had regional recurrence. Five patients (17.2%) required a total laryngectomy, two due to ruptured pexy and three due to local recurrence. Four of these patients (80%) achieved a successful total procedure. Four patients (13.8%) died, two due to postoperative complications and two due to recurrence. Overall, specific, disease-free and total laryngectomy-free survival at 5 years were, respectively, 82.1%; 88.2%; 83.0% and 80.2%. CONCLUSION: Selected patients with intermediate and advanced laryngeal cancer may benefit from supratracheal laryngectomy, that resulted in total laryngectomy-free survival and specific survival of 80.2% and 88.2%, respectively.

The efficacy and safety of mannitol challenge in a workplace setting for assessing asthma prevalence.

OBJECTIVE: There is no standard definition of asthma for epidemiological purposes; most surveys use symptoms and bronchial hyperresponsiveness. Few studies tested mannitol challenge test (MCT) in occupational settings. We sought to determine efficacy and safety of MCT in detecting subjects with asthma symptoms in the workplace. METHODS: In this cross-sectional study we recruited 908 workers in 2 universities; they underwent a respiratory questionnaire, spirometry, skin prick tests, and MCT. RESULTS: Eight hundred and eleven subjects completed the study; 11.1% had a positive MCT; 8.14% had asthma. MCT had low sensitivity (35.4-61.9%) but high specificity (90.2-94.9%) to detect symptomatic individuals. The most prevalent symptom was wheezing in the last 12 months. Twenty-four of those with a positive MCT (26.7%) had no positive replies to the questions on asthma symptoms. Among subjects with a positive MCT, 71.9% achieved 95% of baseline FEV1 after 15 minutes of salbutamol recovery treatment. Nine subjects (1.1%) had adverse events that prevented the test from being completed. CONCLUSIONS: MCT has high specificity but low sensitivity to detect symptomatic subjects in the workplace. It may detect subjects with hyperresponsiveness but no symptoms, who could be at risk of developing airway diseases. The test is safe and well tolerated.

Asthma self-management model: randomized controlled trial.

Information for patients provided by the pharmacist is reflected in adhesion to treatment, clinical results and patient quality of life. The objective of this study was to assess an asthma self-management model for rational medicine use. This was a randomized controlled trial with 60 asthmatic patients assigned to attend five modules presented by a pharmacist (intervention group) and 59 patients in the control group. Data collection was performed before and after this 4-month intervention and included an evaluation of asthma knowledge, lifestyle, inhaler techniques, adhesion to treatment, pulmonary function and quality of life. An economic viability analysis was also performed. The intervention group obtained an increase in asthma knowledge scores of 58.3-79.5% (P < 0.001). In this group, there was also an increase in the number of individuals who practiced physical exercise (36-43%), in the number of correct replies regarding the use of inhalers, in the percentage of adherent patients, and in quality of life scores for all domains. We concluded that this asthma self-management model was effective in improving the quality of life of asthma patients.

Prevalence of human papillomavirus types and variants and p16(INK4a) expression in head and neck squamous cells carcinomas in São Paulo, Brazil.

BACKGROUND: Human papillomavirus (HPV) prevalence in head and neck squamous cell carcinomas (HNSCC) diverges geographically. The reliability of using p16(INK4a) expression as a marker of viral infection is controversial in HNSCC. We evaluated HPV types and HPV-16 variants prevalence, and p16(INK4a) expression in HNSCC specimens provided by two different Institutions in São Paulo. METHODS: HPV DNA from formalin-fixed specimens was accessed by Inno-LiPA, HPV-16 variants by PCR-sequencing, and p16(INK4a) protein levels by immunohistochemistry. RESULTS: Overall, HPV DNA was detected among 19.4 % of the specimens (36/186). Viral prevalence was higher in the oral cavity (25.0 %, 23/92) then in other anatomical sites (oropharynx 14,3 %, larynx 13.7 %) when samples from both Institutions were analyzed together. HPV prevalence was also higher in the oral cavity when samples from both Institutions were analyzed separately. HPV-16 was the most prevalent type identified in 69.5 % of the HPV positive smaples and specimens were assigned into Asian-American (57.2 %) or European (42.8 %) phylogenetic branches. High expression of p16(INK4a) was more common among HPV positive tumors. CONCLUSION: Our results support a role for HPV-16 in a subset of HNSCC.

BRAF mutation in the elderly submitted to thyroidectomy.

OBJECTIVE: To evaluate the frequency of the BRAF V600E mutation in patients over 65 years of age undergoing thyroidectomy, correlating its presence or absence with the different histologic lesions, their variants and with prognostic factors of papillary carcinoma. METHODS: We evaluated 85 patients over 65 years of age who underwent thyroidectomy, analyzing the BRAF V600E mutation by RT-PCR performed after DNA extraction from the paraffin blocks. RESULTS: The study detected the presence or absence of BRAF V600E mutation in 47 patients (55.3%). Among the 17 papillary carcinomas studied, seven had the mutation (41.2%). There was a statistical association between the presence of this mutation and the classic variant of papillary carcinoma, and a trend of association with thyroid extravasation. CONCLUSION: BRAF mutation in the elderly is also exclusive of papillary carcinoma and is often significant. Furthermore, it is related to the classic variant and possibly to thyroid extravasation.

Mutação BRAF em pacientes idosos submetidos à tireoidectomia / BRAF mutation in the elderly submitted to thyroidectomy

OBJETIVO: Avaliar a frequência da mutação V600E do gene BRAF em pacientes com mais de 65 anos de idade submetidos à tireoidectomia, correlacionando sua presença ou ausência com as diferentes lesões histológicas, com as variantes e com fatores prognósticos do carcinoma papilífero. MÉTODOS: Foram avaliados 85 pacientes com mais de 65 anos de idade submetidos à tireoidectomia, analisando a mutação BRAF V600E através de reação de PCR-RT realizada após a extração do DNA dos blocos de parafina. RESULTADOS: Detectou-se ausência ou presença da mutação BRAF V600E em 47 pacientes (55,3%). Entre os 17 carcinomas papilíferos estudados, sete apresentavam a mutação (41,2%). Demonstrou-se associação estatística entre a presença desta mutação e a variante clássica do carcinoma papilífero, além de tendência de associação com o extravasamento tireoideano. CONCLUSÃO: A mutação BRAF nos pacientes idosos também é exclusiva do carcinoma papilífero e tem frequência expressiva. Além disso, está relacionada à variante clássica e, possivelmente, ao extravasamento tireoideano.

OBJECTIVE: To evaluate the frequency of the BRAF V600E mutation in patients over 65 years of age undergoing thyroidectomy, correlating its presence or absence with the different histologic lesions, their variants and with prognostic factors of papillary carcinoma. METHODS: We evaluated 85 patients over 65 years of age who underwent thyroidectomy, analyzing the BRAF V600E mutation by RT-PCR performed after DNA extraction from the paraffin blocks. RESULTS: The study detected the presence or absence of BRAF V600E mutation in 47 patients (55.3%). Among the 17 papillary carcinomas studied, seven had the mutation (41.2%). There was a statistical association between the presence of this mutation and the classic variant of papillary carcinoma, and a trend of association with thyroid extravasation. CONCLUSION: BRAF mutation in the elderly is also exclusive of papillary carcinoma and is often significant. Furthermore, it is related to the classic variant and possibly to thyroid extravasation.

Tromboembolismo pulmonar / Pulmonary thromboembolism

O tromboembolismo pulmonar (TEP) tem quadro clínico bastante variável, que vai desde quadros completamente assintomáticos, nos quais o diagnóstico é feito incidentalmente, até situações em que êmbolos maciços levam o paciente rapidamente à morte. Seu diagnóstico é difícil e depende da análise da probabilidade pré-teste para otimização da acurácia dos métodos diagnósticos complementares. Apedra angular do tratamento é anti-coagulação, porém a trombólise química deve ser considerada em casos de instabilidade hemodinâmica.

Pulmonary embolism (PE) has highly variable clinical presentation, ranging from completely asymptomaticpatients, in which the diagnosis is made incidentally, to situations where massive emboli lead thepatient quickly to death. Its diagnosis is difficult and depends on analysis of pre-test probability foroptimum accuracy of diagnostic procedures. The hallmark of treatment is anticoagulation, but the chemicalthrombolysis should be considered in cases of hemodynamic instability.

Inflammatory and functional effects of increasing asthma treatment with formoterol or double dose budesonide.

Adding a long-acting beta(2)-agonist to inhaled corticosteroids (ICS) for asthma treatment is better than increasing ICS dose in improving clinical status, although there is no consensus about the impact of this regimen on inflammation. In this double-blind, randomized, parallel group study, asthmatics with moderate to severe disease used budesonide (400 mcg/day) for 5 weeks (run-in period); then they were randomized to use budesonide (800 mcg/day--BUD group) or budesonide plus formoterol (400 mcg and 24 mcg/day, respectively--FORMO group) for 9 weeks (treatment period). Home PEF measurements, symptom daily reporting, spirometry, sputum induction (for differential cell counts and sputum cell cultures), and hypertonic saline bronchial challenge test were performed before and after treatments. TNF-alpha, IL-4 and eotaxin-2 levels in the sputum and cell culture supernatants were determined. Morning and night PEF values increased in the FORMO group during the treatment period (p<0.01), from 435+/-162 to 489+/-169 and 428+/-160 to 496+/-173 L/min, respectively. The rate of exacerbations in the FORMO group was lower than in the BUD group (p<0.05). Neutrophil counts in sputum increased in both groups (p<0.05) and leukocyte viability after 48 h-culture increased in the FORMO group (p<0.05). No other parameter changed significantly in either group. This study showed that adding formoterol to budesonide improved home PEF and provided protection from exacerbations, although increase of leukocyte viability in cell culture may be a matter of concern and needs further investigation.

Epidemiological and histopathological data and E-cadherin-like prognostic factors in early carcinomas of the tongue and floor of mouth.

Despite recent advances in diagnosis and treatment, overall survival of people with squamous cell carcinomas of the tongue and mouth floor continues to be low. Prognostic information is essential for improved evaluation and treatment. A molecular approach is necessary for a better understanding of cancer. We analyzed 50 patients with early squamous cell carcinoma (stages I and II - AJCC, 1997), who were surgically treated in head and neck departments at Heliopolis Hospital and Santa Casa in São Paulo, Brazil. We searched for epidemiological and pathological behaviors that could be involved in tumor recurrence and the influence of cellular adhesion loss in patient outcome. We established two groups: patients with disease recurrence within 3 years of follow-up and patients with no cancer recurrence in this period. Significant prognostic variables included age, daily alcohol intake, neural invasion and maximum tumor thickness. Our findings are similar to other published data in which younger patients have a better prognosis. The odds ratio for neural invasion was low but was significant for thickness. No significant difference was observed among groups in E-cadherin expression. Our data suggest that 3 and 5mm are the prognostic determinants of thickness. E-cadherin mutation was not related to recurrences but was associated with locally aggressive invasion patterns.