Recommendations for head and neck surgical procedures during the COVID-19 pandemic.

The coronavirus disease (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread exponentially worldwide. In Brazil, the number of infected people diagnosed has been increasing and, as in other countries, it has been associated with a high risk of contamination in healthcare teams. For healthcare professionals, the full use of personal protective equipment (PPE) is mandatory, such as wearing surgical or filtering facepiece class 2 (FFP2) masks, waterproof aprons, gloves, and goggles, in addition to training in care processes. A reduction in the number of face-to-face visits and non-essential elective procedures is also recommended. However, surgery should not be postponed in the case of the most essential elective indications (mostly associated with head and neck cancers). As malignant tumors of the head and neck are clinically time sensitive, neither consultations for these tumors nor their treatment should be postponed. Postponing surgical treatment can result in a change in the disease stage and alter an individual's chance of survival. In this situation, planning of all treatments must begin with the request for, in addition to routine examinations, a nasal swab polymerase chain reaction for SARS-CoV-2 and chest computed tomography. Only if the results of these tests are positive or if fever or other symptoms suggestive of COVID-19 are present should the surgical procedure be postponed until the patient completely recovers. This is mandatory not only because of the risk of contamination of the surgical team but also because of the increased risk of postoperative complications and high risk of death. During this pandemic, the most effective safety measures are social distancing for the general public and the adequate availability and use of PPE in the healthcare field. The treatment of other chronic diseases, such as cancer, should be continued, as the damming of cases of these diseases will have a deleterious effect on the public healthcare system.

Recommendations for head and neck surgical procedures during the COVID-19 pandemic

The coronavirus disease (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread exponentially worldwide. In Brazil, the number of infected people diagnosed has been increasing and, as in other countries, it has been associated with a high risk of contamination in healthcare teams. For healthcare professionals, the full use of personal protective equipment (PPE) is mandatory, such as wearing surgical or filtering facepiece class 2 (FFP2) masks, waterproof aprons, gloves, and goggles, in addition to training in care processes. A reduction in the number of face-to-face visits and non-essential elective procedures is also recommended. However, surgery should not be postponed in the case of the most essential elective indications (mostly associated with head and neck cancers). As malignant tumors of the head and neck are clinically time sensitive, neither consultations for these tumors nor their treatment should be postponed. Postponing surgical treatment can result in a change in the disease stage and alter an individual's chance of survival. In this situation, planning of all treatments must begin with the request for, in addition to routine examinations, a nasal swab polymerase chain reaction for SARS-CoV-2 and chest computed tomography. Only if the results of these tests are positive or if fever or other symptoms suggestive of COVID-19 are present should the surgical procedure be postponed until the patient completely recovers. This is mandatory not only because of the risk of contamination of the surgical team but also because of the increased risk of postoperative complications and high risk of death. During this pandemic, the most effective safety measures are social distancing for the general public and the adequate availability and use of PPE in the healthcare field. The treatment of other chronic diseases, such as cancer, should be continued, as the damming of cases of these diseases will have a deleterious effect on the public healthcare system.

Diagnosis, treatment, and follow-up of medullary thyroid carcinoma: recommendations by the Thyroid Department of the Brazilian Society of Endocrinology and Metabolism.

INTRODUCTION: Medullary thyroid carcinoma (MTC) originates in the thyroid parafollicular cells and represents 3-4% of the malignant neoplasms that affect this gland. Approximately 25% of these cases are hereditary due to activating mutations in the REarranged during Transfection (RET) proto-oncogene. The course of MTC is indolent, and survival rates depend on the tumor stage at diagnosis. The present article describes clinical evidence-based guidelines for the diagnosis, treatment, and follow-up of MTC. OBJECTIVE: The aim of the consensus described herein, which was elaborated by Brazilian experts and sponsored by the Thyroid Department of the Brazilian Society of Endocrinology and Metabolism, was to discuss the diagnosis, treatment, and follow-up of individuals with MTC in accordance with the latest evidence reported in the literature. MATERIALS AND METHODS: After clinical questions were elaborated, the available literature was initially surveyed for evidence in the MedLine-PubMed database, followed by the Embase and Scientific Electronic Library Online/Latin American and Caribbean Health Science Literature (SciELO/Lilacs) databases. The strength of evidence was assessed according to the Oxford classification of evidence levels, which is based on study design, and the best evidence available for each question was selected. RESULTS: Eleven questions corresponded to MTC diagnosis, 8 corresponded to its surgical treatment, and 13 corresponded to follow-up, for a total of 32 recommendations. The present article discusses the clinical and molecular diagnosis, initial surgical treatment, and postoperative management of MTC, as well as the therapeutic options for metastatic disease. CONCLUSIONS: MTC should be suspected in individuals who present with thyroid nodules and family histories of MTC, associations with pheochromocytoma and hyperparathyroidism, and/or typical phenotypic characteristics such as ganglioneuromatosis and Marfanoid habitus. Fine-needle nodule aspiration, serum calcitonin measurements, and anatomical-pathological examinations are useful for diagnostic confirmation. Surgery represents the only curative therapeutic strategy. The therapeutic options for metastatic disease remain limited and are restricted to disease control. Judicious postoperative assessments that focus on the identification of residual or recurrent disease are of paramount importance when defining the follow-up and later therapeutic management strategies.

Diagnóstico, tratamento e seguimento do carcinoma medular de tireoide: recomendações do Departamento de Tireoide da Sociedade Brasileira de Endocrinologia e Metabologia / Diagnosis, treatment, and follow-up of medullary thyroid carcinoma: recommendations by the Thyroid Department of the Brazilian Society of Endocrinology and Metabolism

Introdução O carcinoma medular de tireoide (CMT) origina-se das células parafoliculares da tireoide e corresponde a 3-4% das neoplasias malignas da glândula. Aproximadamente 25% dos casos de CMT são hereditários e decorrentes de mutações ativadoras no proto-oncogene RET (REarranged during Transfection). O CMT é uma neoplasia de curso indolente, com taxas de sobrevida dependentes do estádio tumoral ao diagnóstico. Este artigo descreve diretrizes baseadas em evidências clínicas para o diagnóstico, tratamento e seguimento do CMT. Objetivo O presente consenso, elaborado por especialistas brasileiros e patrocinado pelo Departamento de Tireoide da Sociedade Brasileira de Endocrinologia e Metabologia, visa abordar o diagnóstico, tratamento e seguimento dos pacientes com CMT, de acordo com as evidências mais recentes da literatura. Materiais e métodos: Após estruturação das questões clínicas, foi realizada busca das evidências disponíveis na literatura, inicialmente na base de dados do MedLine-PubMed e posteriormente nas bases Embase e SciELO – Lilacs. A força das evidências, avaliada pelo sistema de classificação de Oxford, foi estabelecida a partir do desenho de estudo utilizado, considerando-se a melhor evidência disponível para cada questão. Resultados Foram definidas 11 questões sobre o diagnóstico, 8 sobre o tratamento cirúrgico e 13 questões abordando o seguimento do CMT, totalizando 32 recomendações. Como um todo, o artigo aborda o diagnóstico clínico e molecular, o tratamento cirúrgico inicial, o manejo pós-operatório e as opções terapêuticas para a doença metastática. Conclusões O diagnóstico de CMT deve ser suspeitado na presença de nódulo tireoidiano e história ...

Introduction Medullary thyroid carcinoma (MTC) originates in the thyroid parafollicular cells and represents 3-4% of the malignant neoplasms that affect this gland. Approximately 25% of these cases are hereditary due to activating mutations in the REarranged during Transfection (RET) proto-oncogene. The course of MTC is indolent, and survival rates depend on the tumor stage at diagnosis. The present article describes clinical evidence-based guidelines for the diagnosis, treatment, and follow-up of MTC. Objective The aim of the consensus described herein, which was elaborated by Brazilian experts and sponsored by the Thyroid Department of the Brazilian Society of Endocrinology and Metabolism, was to discuss the diagnosis, treatment, and follow-up of individuals with MTC in accordance with the latest evidence reported in the literature. Materials and methods: After clinical questions were elaborated, the available literature was initially surveyed for evidence in the MedLine-PubMed database, followed by the Embase and Scientific Electronic Library Online/Latin American and Caribbean Health Science Literature (SciELO/Lilacs) databases. The strength of evidence was assessed according to the Oxford classification of evidence levels, which is based on study design, and the best evidence available for each question was selected. Results Eleven questions corresponded to MTC diagnosis, 8 corresponded to its surgical treatment, and 13 corresponded to follow-up, for a total of 32 recommendations. The present article discusses the clinical and molecular diagnosis, initial surgical treatment, and postoperative management of MTC, as well as the therapeutic options for metastatic disease. Conclusions 7 .

Expression of SMAD proteins, TGF-beta/activin signaling mediators, in human thyroid tissues.

OBJECTIVE: To investigate the expression of SMAD proteins in human thyroid tissues since the inactivation of TGF-beta/activin signaling components is reported in several types of cancer. Phosphorylated SMAD 2 and SMAD3 (pSMAD2/3) associated with the SMAD4 induce the signal transduction generated by TGF-beta and activin, while SMAD7 inhibits this intracellular signaling. Although TGF-beta and activin exert antiproliferative roles in thyroid follicular cells, thyroid tumors express high levels of these proteins. MATERIALS AND METHODS: The protein expression of SMADs was evaluated in multinodular goiter, follicular adenoma, papillary and follicular carcinomas by immunohistochemistry. RESULTS: The expression of pSMAD2/3, SMAD4 and SMAD7 was observed in both benign and malignant thyroid tumors. Although pSMAD2/3, SMAD4 and SMAD7 exhibited high cytoplasmic staining in carcinomas, the nuclear staining of pSMAD2/3 was not different between benign and malignant lesions. CONCLUSIONS: The finding of SMADs expression in thyroid cells and the presence of pSMAD2/3 and SMAD4 proteins in the nucleus of tumor cells indicates propagation of TGF-beta/activin signaling. However, the high expression of the inhibitory SMAD7, mostly in malignant tumors, could contribute to the attenuation of the SMADs antiproliferative signaling in thyroid carcinomas.

Expression of SMAD proteins, TGF-beta/activin signaling mediators, in human thyroid tissues / Expressão de proteínas SMAD, mediadores da sinalização de TGF-beta/activina, em tecidos de tiroide humana

OBJECTIVE: To investigate the expression of SMAD proteins in human thyroid tissues since the inactivation of TGF-β/activin signaling components is reported in several types of cancer. Phosphorylated SMAD 2 and SMAD3 (pSMAD2/3) associated with the SMAD4 induce the signal transduction generated by TGF-β and activin, while SMAD7 inhibits this intracellular signaling. Although TGF-β and activin exert antiproliferative roles in thyroid follicular cells, thyroid tumors express high levels of these proteins. MATERIALS AND METHODS: The protein expression of SMADs was evaluated in multinodular goiter, follicular adenoma, papillary and follicular carcinomas by immunohistochemistry. RESULTS: The expression of pSMAD2/3, SMAD4 and SMAD7 was observed in both benign and malignant thyroid tumors. Although pSMAD2/3, SMAD4 and SMAD7 exhibited high cytoplasmic staining in carcinomas, the nuclear staining of pSMAD2/3 was not different between benign and malignant lesions. CONCLUSIONS: The finding of SMADs expression in thyroid cells and the presence of pSMAD2/3 and SMAD4 proteins in the nucleus of tumor cells indicates propagation of TGF-β/activin signaling. However, the high expression of the inhibitory SMAD7, mostly in malignant tumors, could contribute to the attenuation of the SMADs antiproliferative signaling in thyroid carcinomas.

OBJETIVO: Investigar a expressão de proteínas SMAD em tecidos de tiroide humana desde que a inativação dos componentes da sinalização de TGF-β/activina é relatada em diversos tipos de câncer. SMAD 2 e SMAD3 fosforilados (pSMAD2/3) associados com SMAD4 induzem a transmissão do sinal gerado por TGF-β e activina, enquanto SMAD7 inibe essa sinalização intracelular. Embora TGF-β e activina exerçam efeitos antiproliferativos nas células foliculares da tiroide, tumores de tiroide expressam altos níveis dessas proteínas. MATERIAIS E MÉTODOS: A expressão proteica de SMADs foi avaliada em bócio multinodular, adenoma folicular, carcinomas papilífero e folicular por imuno-histoquímica. RESULTADOS: A expressão de pSMAD2/3, SMAD4 e SMAD7 foi observada tanto em tumores benignos como malignos da tiroide. Embora pSMAD2/3, SMAD4 e SMAD7 exibissem alta positividade citoplasmática em carcinomas, a positividade nuclear de pSMAD2/3 não foi diferente entre lesões benignas e malignas da tiroide. CONCLUSÕES: O achado da expressão de SMADs em células tiroidianas e a presença das proteínas pSMAD2/3 e SMAD4 no núcleo de células tumorais indicam propagação da sinalização TGF-β/activina. Contudo, a alta expressão de SMAD7 inibitório, principalmente em tumores malignos, poderia contribuir para atenuação da sinalização antiproliferativa de SMADs em carcinomas de tiroide.

Thyroid tissue analysis through Raman spectroscopy.

The diagnosis of thyroid pathologies is usually made by cytologic analysis of the fine needle aspiration (FNA) material. However, this procedure has a low sensitivity at times, presenting a variation of 2-37%. The application of optical spectroscopy in the characterization of alterations could result in the development of a minimally invasive and non-destructive method for the diagnosis of thyroid diseases. Thus, the objective of this work was to study the biochemical alterations of tissues and hormones (T3 and T4) of the thyroid gland by means of molecular vibrations probed by FT-Raman spectroscopy. Through the discriminative linear analysis of the Raman spectra of the tissue, it was possible to establish (in percentages) the correct classification index among the groups: goitre adjacent tissue, goitre nodular region, follicular adenoma, follicular carcinoma and papillary carcinoma. As a result of the comparison between the groups goitre adjacent tissue versus goitre nodular region, an index of 58.3% of correct classification was obtained; this percentage was considered low, and it was not possible to distinguish the Raman spectra of these groups. Between goitre (nodular region and adjacent tissue) versus papillary carcinoma, the index of correct classification was 64.9%, which was considered good. A relevant result was obtained in the analysis of the benign tissues (goitre and follicular adenoma) versus malignant tissues (papillary and follicular carcinomas), for which the index was 72.5% and considered good. It was also possible, by means of visual observation, to find similar vibrational modes in the hormones and pathologic tissues. In conclusion, some biochemical alterations, represented by the FT-Raman spectra, were identified that could possibly be used to classify histologic groups of the thyroid. However, more studies are necessary due to the difficulty in setting a standard for pathologic groups.

Anatomic landmarks for localization of the spinal accessory nerve.

This anatomical study examines the anatomic topography and landmarks for localization of the spinal accessory nerve (SAN) during surgical dissections in 40 fresh human cadavers (2 females and 38 males; ages from 22 to 89 years with a mean of 60 years). In the submandibular region, the SAN was found anteriorly to the transverse process of the atlas in 77.5% of the dissections. When the SAN crossed the posterior belly of the digastric muscle, the mean distance from the point of crossing to the tendon of the muscle was 1.75 +/- 0.54 cm. Distally, the SAN crossed between the two heads of the SCM muscle in 45% of the dissections and deep to the muscle in 55%. The SAN exited the posterior border of the sternocleidomastoid muscle in a point superior to the nerve point with a mean distance between these two anatomic parameters of 0.97 +/- 0.46 cm. The mean overall extracranial length of the SAN was 12.02 +/- 2.32 cm, whereas the mean length of the SAN in the posterior triangle was 5.27 +/- 1.52 cm. There were 2-10 lymph nodes in the SAN chain. In conclusion, the nerve point is one of the most reliable anatomic landmarks for localization of the SAN in surgical neck dissections. Although other anatomic parameters including the transverse process of the atlas and the digastric muscle can also be used to localize the SAN, the surgeon should be aware of the possibility of anatomic variations of those parameters. Similar to previous investigations, our results suggest that the number of lymph nodes of the SAN chain greatly varies.

Association of low sodium-iodide symporter messenger ribonucleic acid expression in malignant thyroid nodules with increased intracellular protein staining.

CONTEXT: The expression of sodium iodide symporter (NIS) is required for iodide uptake in thyroid cells. Benign and malignant thyroid tumors have low iodide uptake. However, previous studies by RT-PCR or immunohistochemistry have shown divergent results of NIS expression in these nodules. OBJECTIVE: The objective of the study was to investigate NIS mRNA transcript levels, compare with NIS and TSH receptor proteins expression, and localize the NIS protein in thyroid nodules samples and their surrounding nonnodular tissues (controls). DESIGN: NIS mRNA levels, quantified by real-time RT-PCR, and NIS and TSH receptor proteins, evaluated by immunohistochemistry, were examined in surgical specimens of 12 benign and 13 malignant nodules and control samples. RESULTS: When compared with controls, 83.3% of the benign and 100% of the malignant nodules had significantly lower NIS gene expression. Conversely, 66.7% of the benign and 100% of malignant nodules had stronger intracellular NIS immunostaining than controls. Low gene expression associated with strong intracellular immunostaining was most frequently detected in malignant (100%) than benign nodules (50%; P = 0.005). NIS protein was located at the basolateral membrane in 24% of the control samples, 8.3% of the benign, and 15.4% of the malignant nodules. The percentage of benign nodules with strong TSH receptor positivity (41.6%) was higher than malignant (7.7%). CONCLUSION: We confirmed that reduced NIS mRNA expression in thyroid malignant nodules is associated with strong intracellular protein staining and may be related to the inability of the NIS protein to migrate to the cellular basolateral membrane. These results may explain the low iodide uptake of malignant nodules.

Total thyroidectomy for benign thyroid disease.

OBJECTIVES/HYPOTHESIS: The use of total thyroidectomy in thyroid cancer treatment is not unanimous, and it is even more controversial when this procedure is advocated for benign diseases. On the other hand, the complication risk may have an increase up to 20 times in repeat operations for recurrence. The objective of the study was to evaluate the use of total thyroidectomy in benign diseases, multinodular goiter, and Graves disease to justify the authors' preference. STUDY DESIGN: Retrospective study of use of total thyroidectomy in benign diseases. METHODS: Retrospective study of 1789 patients who underwent thyroidectomies from June 1990 to December 2000. Indication, extension of thyroidectomy, cancer incidence, and complications were analyzed. RESULTS: Total thyroidectomy was performed in 81.19% of 456 patients with nontoxic multinodular goiter, 93.93% of 33 with toxic multinodular goiter, 93.93% of 66 with recurrent multinodular goiter, and 49.18% of 122 with Graves disease. Thyroid cancer was found in 16.62%, 9.09%, 3.03% and 5.73% of patients, respectively. Transitory and permanent hypoparathyroidism, hematoma requiring surgical intervention, and transitory and permanent recurrent laryngeal nerve injury occurred in 12.27%, 1.61%, 0.26%, 1.88%, and 0.35% of the patients undergoing total thyroidectomy, respectively. Permanent complications of total thyroidectomy for nontoxic multinodular goiter and Graves disease were similar to nontotal thyroidectomy. Use of total thyroidectomy for nontoxic multinodular goiter increased from 53.33% of the patient to 81.19%, on average, with a concomitant increase of cancer diagnosis from 11.11% to 16,62%. The authors performed total thyroidectomy for all patients with Graves disease. CONCLUSION: Total thyroidectomy is the treatment of choice for multinodular goiter and thyroiditis, when there is bilateral gland involvement posterior to middle thyroid veins, and for Graves disease because it decreases the likelihood of future repeat operations for recurrent disease and thus the associated risks, when performed safely.

Tireoidectomia total para bócio multinodular / Total thyroidectomy for multinodular goiter

INTRODUÇÄO: Preservar tecido tireóideo em cirurgias para bócio multinodular (BM) näo evita a complementaçäo hormonal e pode gerar recidiva. A reoperaçäo aumenta em até 20 vezes o risco de complicações. Propomos no BM, a tireoidectomia total (TT) como tratamento definitivo quando existe acometimento bilateral do parênquima posterior à veia tireóidea média. OBJETIVO: Avaliar e justificar a utilizaçäo da TT em portadores de BM. MATERIAL E MÉTODO: Estudo retrospectivo de 1.789 pacientes submetidos a tireoidectomias de 06/90 a 12/00. A indicaçäo cirúrgica foi avaliada conforme a apresentaçäo clínica, a extensäo da tireoidectomia, a incidência de câncer e as complicações. RESULTADOS: A TT foi realizada em 81,2 por cento de 872 portadores de BM atóxicos, 93,9 por cento de 33 BM tóxicos e 93,9 por cento de 66 bócios recidivados. Houve hipoparatireoidismo transitório ou definitivo, hematoma e lesöes transitórias ou definitivas do nervo recorrente em respectivamente 11,5 por cento, 0,5 por cento, 0,4 por cento, 2,7 por cento e 0,2 por cento dos pacientes com BM atóxicos, e 8,3 por cento, 8,3 por cento, zero, 5,0 por cento e 5,0 por cento dos com B recidivados. Complicações definitivas da TT para BM atóxico foram semelhantes à tireoidectomia näo total, porém inferiores da TT para B recidivado. Ocorreu aumento da indicaçäo da TT para BM atóxico, com a utilizaçäo da veia tireóidea média como referência anatômica, de 53,3 por cento inicialmente para 93,6 por cento atualmente, com elevaçäo do diagnóstico de câncer de 11,1 por cento para 19,8 por cento. CONCLUSÄO: TT é o tratamento de escolha para o BM, quando acomete extensamente a glândula, isto é, posteriormente às veias tireóideas médias; com baixo índice de complicações definitivas

Activin betaB expression in rat experimental goiter and human thyroid tumors.

Activins are dimeric proteins of the transforming growth factor beta superfamily, which exhibit multiple functions in gonadal and extragonadal tissues. Expression of activin A, composed of two betaA subunits, has been shown in the thyroid, whereas there has been no study regarding activin B (betaBbetaB) in this gland. In other tissues, such as the gonads, pancreas, and adrenal cortex, expression of both activin betaA and activin betaB has been described. In this study, we detected activin betaB mRNA and protein expression using reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry in rat experimental goiter and in human thyroid, including multinodular goiter, follicular adenoma, papillary carcinoma, and follicular carcinoma. Activin betaA mRNA and protein expression was also investigated in rat and human thyroid tissue. The expression of both activin betaB and activin betaA was highest in rat methimazole-induced goiter and in human follicular adenoma, and papillary and follicular carcinomas when compared with multinodular goiter and normal thyroid tissue. The increased expression of activin betaB as well as activin betaA, observed in this study, suggests that activin B and activin A may be involved in the proliferative and neoplastic processes of the thyroid.