Analysis of the status of treatment of benign thyroid diseases - a public health problem aggravated in the COVID-19 pandemic era / Análise da situação do tratamento das doenças benignas da tireoide - Um problema de saúde pública agravado pela pandemia de Covid-19

Abstract Objective: Goiters and benign nodules detected in the thyroid are growing lesions and the COVID-19 pandemic have negatively impacted on their surgical treatment. The appropriate selection of patients to treatment will improve the overall health status. This article review will focus on the impact of the COVID-19 pandemic on treatment of benign conditions of the thyroid gland and their implications. Methods: This review pointed out the status of the health system in developing country and the problems to treat benign surgical diseases of thyroid. Aspects of epidemiology, incidence, clinical presentation and surgical treatment of goiters, economic and health status impact were cited. Results: All surgical treatment of goiter and other benign conditions were postponed, forced to redirect, and reschedule all benign surgeries, situation aggravated by poor public management and closure of hospital beds. These conditions have caused deterioration in patients' physical (decompensated thyroid disease) and mental health status, increasing work disabilities and burdening society by increasing the social and health cost. The overall situation could be catastrophic in emergent countries where this increased disease-related social expenditure on surgical treatment may increase the risk of national impoverishment as increase the treatment cost. Brazilian Society Head and Neck Surgery related some recommendations and new suggestions were made to safely treat these high potential hazard surgical conditions. Conclusions: Surgeries for goiter and benign thyroid conditions can be performed during the COVID-19 pandemic, following strict safety protocols for the patient and the medical team, reducing the negative economic and on patient health impact.

Resumo Objetivo: Bócios e nódulos benignos detectados na tireoide são lesões em crescimento e a pandemia de Covid-19 impactou negativamente seu tratamento cirúrgico. A seleção adequada de pacientes para o tratamento vai melhorar o estado geral de saúde. Esta revisão de artigos se concentrará no impacto da pandemia de Covid-19 no tratamento de condições benignas da glândula tireoide e suas implicações. Método: Esta revisão evidenciou a situação do sistema de saúde em países em desenvolvimento e os problemas para tratar doenças cirúrgicas benignas da tireoide. Aspectos da epidemiologia, incidência, apresentação clínica e tratamento cirúrgico do bócio, impacto econômico e no estado de saúde foram relatados. Resultados: Todos os tratamentos cirúrgicos de bócio e outras condições benignas foram adiados, forçados a se redirecionar e a remarcar todas as cirurgias benignas, situação agravada pela má gestão pública e fechamento de leitos hospitalares. Essas condições têm causado deterioração do estado de saúde física (doença da tireoide descompensada) e mental dos pacientes, aumentam as incapacidades para o trabalho e sobrecarregando a sociedade e o custo social e de saúde. A situação geral pode ser catastrófica em países emergentes, onde esse aumento dos gastos sociais relacionados à doença sob tratamento cirúrgico pode aumentar o risco de empobrecimento nacional à medida que aumenta o custo do tratamento. A Sociedade Brasileira de Cirurgia de Cabeça e Pescoço forneceu algumas recomendações e novas sugestões foram feitas para tratar com segurança essas condições cirúrgicas de alto risco potencial. Conclusão: As cirurgias para bócio e condições benignas da tireoide podem ser feitas durante a pandemia de Covid-19, se forem seguidos rigorosos protocolos de segurança para o paciente e equipe médica, o que reduz o impacto negativo na economia e na saúde do paciente.

Analysis of the status of treatment of benign thyroid diseases - a public health problem aggravated in the COVID-19 pandemic era.

OBJECTIVE: Goiters and benign nodules detected in the thyroid are growing lesions and the COVID-19 pandemic have negatively impacted on their surgical treatment. The appropriate selection of patients to treatment will improve the overall health status. This article review will focus on the impact of the COVID-19 pandemic on treatment of benign conditions of the thyroid gland and their implications. METHODS: This review pointed out the status of the health system in developing country and the problems to treat benign surgical diseases of thyroid. Aspects of epidemiology, incidence, clinical presentation and surgical treatment of goiters, economic and health status impact were cited. RESULTS: All surgical treatment of goiter and other benign conditions were postponed, forced to redirect, and reschedule all benign surgeries, situation aggravated by poor public management and closure of hospital beds. These conditions have caused deterioration in patients' physical (decompensated thyroid disease) and mental health status, increasing work disabilities and burdening society by increasing the social and health cost. The overall situation could be catastrophic in emergent countries where this increased disease-related social expenditure on surgical treatment may increase the risk of national impoverishment as increase the treatment cost. Brazilian Society Head and Neck Surgery related some recommendations and new suggestions were made to safely treat these high potential hazard surgical conditions. CONCLUSIONS: Surgeries for goiter and benign thyroid conditions can be performed during the COVID-19 pandemic, following strict safety protocols for the patient and the medical team, reducing the negative economic and on patient health impact.

Incidence of contralateral cervical metastasis in laryngeal tumors

Introduction: Through the knowledge of the metastatic pathways of the Squamous Cell Carcinoma (SCC) of the larynx, the lymph node level with a higher probability of involvement can be predicted. The surgeon uses this knowledge to determine the extension of neck dissection to perform. However, the longer the surgery, the greater the morbidity for the patient. When the metastatic risk is >20%, neck dissection of that cervical level is necessary. In cases of clinically evident (cN+) metastasis, uni or bilaterally, comprehensive neck dissection is determinant for the treatment, however there is no consensus about neck dissection for contralateral clinically negative neck (cN-). Objective: To evaluate if patients with laryngeal SCC homolateral cN+ and contralateral cN- should be submitted to bilateral neck dissection. Methods: The team reviewed medical records from 135 patients with a diagnosis of laryngeal malignancy between March/2009 and September/2017, analyzing gender, age, tobacco and alcohol comsumption, primary tumor site, neck dissection laterality, clinical and pathological contralaterality, staging, tumor recurrence or late metastasis and survival Results: We observed that 40.74% were pN+ on at least one side after neck dissection, which 87.27% performed bilateral neck dissection. Of these, 66.67% did not have contralateral metastasis, 87.5% had no previously clinically evident metastasis. Conclusion: Patients contralateral cN- have a risk <20% for occult metastasis and should not routinely go through bilateral neck dissection.

The role of transoral robotic surgery in the management of oropharyngeal cancer.

PURPOSE OF REVIEW: The rising incidence of oropharyngeal squamous cell carcinoma (OPSCC), in large part as a result of the human papillomavirus (HPV), has driven a movement for the change in the management strategies. Renewed interest in minimally invasive approaches of endoscopic head and neck surgery led to introduction of transoral surgery, including transoral robotic surgery (TORS). RECENT FINDINGS: Several recent studies, based on large multi-institutional studies and systematic reviews of the literature, have shown excellent oncologic and functional outcomes with TORS for OPSCC. Also, a growing amount of clinical evidence supports the use of TORS in the management of carcinoma of unknown primary site and in selected patients with recurrent OPSCC with acceptable oncologic and better functional outcomes in comparison with traditional surgical approaches. Comparative studies with other therapeutic modalities (conventional surgical and nonsurgical) showed that TORS can be used to treat OPSCC, reducing morbidity and treatment costs, while providing equivalent oncologic results. SUMMARY: Large and robust data available in the literature supports the role of TORS within the multidisciplinary treatment paradigm for the management of OPSCC. Information from ongoing randomized clinical trials comparing TORS with and without dose-reduced radiotherapy or with and without intensified adjuvant treatment for high-risk OPSCC patients is necessary to determine the role of de-escalation of therapy in the era of HPV and OPSCC.

Hemangiopericitoma de valécula em paciente jovem do sexo masculino: relato de caso / Vallecula hemangiopericytoma in a young male patient: case report

O hemangiopericitoma é um tumor raro em cabeça e pescoço, comlocalização mais frequente na cavidade nasossinusal. Em 1942,quando Stout e Murray aplicaram o termo ?hemangiopericitoma?para essa neoplasia, verificaram que não havia característicasmacroscópicas que permitissem seu reconhecimento ediagnóstico. O tratamento de escolha em qualquer localização éa ressecção cirúrgica ampla, com margens oncológicas. A via deacesso transmento-transglosso é uma boa opção para tumoreslocalizados em parede posterior de orofaringe. O objetivo denosso estudo é relatar um caso de um hemangiopericitomalocalizado em valécula em um paciente jovem do sexo masculino,dada a raridade deste tipo de tumor nessa topografia, bem comodescrever o acesso cirúrgico utilizado.

Four-gene expression model predictive of lymph node metastases in oral squamous cell carcinoma.

BACKGROUND: Previous knowledge of cervical lymph node compromise may be crucial to choose the best treatment strategy in oral squamous cell carcinoma (OSCC). Here we propose a set four genes, whose mRNA expression in the primary tumor predicts nodal status in OSCC, excluding tongue. MATERIAL AND METHODS: We identified differentially expressed genes in OSCC with and without compromised lymph nodes using Differential Display RT-PCR. Known genes were chosen to be validated by means of Northern blotting or real time RT-PCR (qRT-PCR). Thereafter we constructed a Nodal Index (NI) using discriminant analysis in a learning set of 35 patients, which was further validated in a second independent group of 20 patients. RESULTS: Of the 63 differentially expressed known genes identified comparing three lymph node positive (pN +) and three negative (pN0) primary tumors, 23 were analyzed by Northern analysis or RT-PCR in 49 primary tumors. Six genes confirmed as differentially expressed were used to construct a NI, as the best set predictive of lymph nodal status, with the final result including four genes. The NI was able to correctly classify 32 of 35 patients comprising the learning group (88.6%; p = 0.009). Casein kinase 1alpha1 and scavenger receptor class B, member 2 were found to be up regulated in pN + group in contrast to small proline-rich protein 2B and Ras-GTPase activating protein SH3 domain-binding protein 2 which were upregulated in the pN0 group. We validated further our NI in an independent set of 20 primary tumors, 11 of them pN0 and nine pN + with an accuracy of 80.0% (p = 0.012). CONCLUSIONS: The NI was an independent predictor of compromised lymph nodes, taking into the consideration tumor size and histological grade. The genes identified here that integrate our "Nodal Index" model are predictive of lymph node metastasis in OSCC.

Sialoendoscopia: relato dos dois primeiros casos tratados no Brasil, no Hospital Israelita Albert Einstein / Sialoendoscopy: report of the first two cases treated in Brazil, at Albert Einstein Jewish Hospital

Introdução: A sialoendoscopia é um procedimento endoscópico realizado nas glândulas salivares maiores submandibular e parótida, com finalidade diagnóstica e, principalmente, terapêutica. Desenvolvida pelo Prof. Francis Marchal, no final da década de 1990, passou a ser utilizada em diversos países da Europa, da América do Norte e da Ásia. Método: Este é um relato dos dois primeiros pacientes com doença inflamatória calculosa das glândulas salivares maiores submetidos à sialoendoscopia no Brasil, no Hospital Israelita Albert Einstein. Relatos dos Casos: Caso 1 - Paciente do sexo masculino, com 37 anos, com quadro de sialoadenite recidivante de glândula submandibular esquerda, após tentativa malsucedida de papilotomia do ducto de Wharton para retirada do cálculo; Caso 2 - Paciente do sexo masculino, com 57 anos, com sialoadenite calculosa obstrutiva de glândula parótida direita, persistente após parotidectomia subtotal. Em ambos os casos, o diagnóstico de cálculo salivar foi confirmado, seguindo-se a retirada bem sucedida com o uso de um ?basket? acoplado ao sialoendoscópio. O primeiro doente teve alta no mesmo dia e o segundo, no dia seguinte, com resolução completa dos sintomas. Conclusão: Neste relato preliminar, a experiência inicial com estes dois casos operados em nossa Instituição é encorajadora, especialmente no segundo paciente, que havia sido submetido a uma tentativa infrutífera de resolução de seu quadro obstrutivo através de uma parotidectomia convencional. Este procedimento, minimamente invasivo, oferece uma nova opção para a abordagem de doenças não-neoplásicas das glândulas salivar maiores, com baixíssima morbidade operatória e bons resultados funcionais imediatos, com preservação das glândulas afetadas.

Background: Sialoendoscopy is an endoscopic procedure performed in the major salivary glands submandibular and parotid, with diagnostic as well as therapeutic intent. It wasdescribed by Prof. Francis Marchal, at the end of the 1990´s, and was used in several countries of Europe, North America and Asia since thereafter. Method: This is a report of the two first cases with sialolithiasis of the major salivary glands submitted to sialoendoscopy in Brazil, at Albert Einstein Jewish Hospital. Case Reports: Case 1 - 37 year-old male, with recurrent sialolithiasis of the left submandibular gland, after unsuccessful attempt to extract the Stone with a papilotomy of the Wharton?s duct; Case 2 - 57 yearold male, with obstructive sialolithiasis of the right parotid gland, persistent even after a subtotal parotidectomy. In both cases, the diagnosis of sialolithiasis was confirmed by sialoendoscopy, with a subsequent successful endoscopic extraction of the Stones with baskets. The first patient was discharged on the same day of the procedure, whereas the second patient was discharged on the first postoperative Day, with complete resolution of their symptoms. Conclusion: In this preliminary report, the initial experience with these two cases operated on at our Institution is encouraging, especially regarding the second patient, who was previously submitted to a failed attempt to cure his disease with a conventional parotidectomy. This procedure, which is minimally invasive, offers a new option for the management of non-neoplastic diseases of the major salivary glands, with very low morbidity and very good initial results, with preservation of the affected glands.

Smad2 and Smad6 as predictors of overall survival in oral squamous cell carcinoma patients.

BACKGROUND: To test if the expression of Smad1-8 mRNAs were predictive of survival in patients with oral squamous cell carcinoma (SCC). PATIENTS AND METHODS: We analyzed, prospectively, the expression of Smad1-8, by means of Ribonuclease Protection Assay in 48 primary, operable, oral SCC. In addition, 21 larynx, 10 oropharynx and 4 hypopharynx SCC and 65 matched adjacent mucosa, available for study, were also included. For survival analysis, patients were categorized as positive or negative for each Smad, according to median mRNA expression. We also performed real-time quantitative PCR (QRTPCR) to asses the pattern of TGFbeta1, TGFbeta2, TGFbeta3 in oral SCC. RESULTS: Our results showed that Smad2 and Smad6 mRNA expression were both associated with survival in Oral SCC patients. Cox Multivariate analysis revealed that Smad6 positivity and Smad2 negativity were both predictive of good prognosis for oral SCC patients, independent of lymph nodal status (P = 0.003 and P = 0.029, respectively). In addition, simultaneously Smad2- and Smad6+ oral SCC group of patients did not reach median overall survival (mOS) whereas the mOS of Smad2+/Smad6- subgroup was 11.6 months (P = 0.004, univariate analysis). Regarding to TGFbeta isoforms, we found that Smad2 mRNA and TGFbeta1 mRNA were inversely correlated (p = 0.05, R = -0.33), and that seven of the eight TGFbeta1+ patients were Smad2-. In larynx SCC, Smad7- patients did not reach mOS whereas mOS of Smad7+ patients were only 7.0 months (P = 0.04). No other correlations were found among Smad expression, clinico-pathological characteristics and survival in oral, larynx, hypopharynx, oropharynx or the entire head and neck SCC population. CONCLUSION: Smad6 together with Smad2 may be prognostic factors, independent of nodal status in oral SCC after curative resection. The underlying mechanism which involves aberrant TGFbeta signaling should be better clarified in the future.

Glycosphingolipid expression in squamous cell carcinoma of the upper aerodigestive tract.

UNLABELLED: Glycosphingolipids are integral constituents of cellular membrane, arranged in rafts, and with neoplastic cell anti-social behavior, like uncontrolled cell growth, invasiveness, and metastatic potential. AIM: However, there are few studies about glycosphingolipids (GSL) expression in squamous cell carcinoma (SCC). Since GSL are known to be tumor-associated markers we decided to perform a prospective study on the GSL profiles of SCC. METHOD: Specimens of 33 SCC and normal mucosa were obtained and GSLs were extracted and purified by reverse-phase chromatography on C18 column and alkaline hydrolysis in methanol. GSLs were quantified using densitometry of orcinol-stained HPTLC plates. RESULT: A significant increase of GSLs in SCC (3.57 microg/mg) was observed as compared to normal mucosa (1.92 microg/mg). In SCC, an increase of 2 to 3 times in the amounts of CDH, CTH, Globoside, and GM3 was observed in comparison to normal mucosa. The identification of GM3 as well as its increased expression in SCC was confirmed unequivocally by HPTLC immunostaining and indirect immunofluorescence using MAb DH2 (anti-GM3). BY analyzing SCC and normal mucosa CMHs by GC/MS, normal mucosa expresses only glucosylceramide whereas SCC cells express both glucosylceramide and galactosylceramide. CONCLUSION: The increase in the amount of GSLs in tumor tissue may represent changes of cell membrane microdomains resulting from the malignant transformation process, which is responsible for greater cell-cell or cell-matrix interaction thereby increasing their potential for infiltration and metastasis.

Expressão de glicoesfingolipídeos no carcinoma espinocelular do trato aerodigestivo superior / Glycosphingolipid expression in squamous cell carcinoma of the upper aerodigestive tract

Os glicoesfingolipídios (GSLs) são importantes componentes da membrana celular, organizados em microdomínios, relacionados a receptores de membrana e comportamento anti-social da célula neoplásica como crescimento descontrolado, invasão e ocorrência de metástases. OBJETIVO: Como a expressão de GSLs no carcinoma espinocelular (CEC) é tema pouquíssimo estudado decidiu-se realizar estudo prospectivo visando avaliar a expressão de GSLs no CEC do trato aerodigestivo superior. MÉTODO: Coletou-se 33 amostras de CEC e mucosa normal e GSLs extraídos e purificados por cromatografia de fase reversa em coluna de C-18 e hidrólise alcalina em metanol. Os GSLs foram quantificados por densitometria das placas de cromatografia de alta resolução em camada delgada coradas com orcinol. RESULTADOS: Observou-se aumento significativo de GSLs no CEC (3,57æg/mg) em comparação à mucosa normal (1,92æg/mg), principalmente do monosialogangliosídeo (GM3), trihexosilceramida (CTH), dihexosilceramida (CDH), globosídeo (Gb4). A expressão de monohexosilceramida (CMH) foi semelhante no CEC e na mucosa normal. O aumento do GM3 no CEC foi demonstrado por métodos imunoquímicos empregando-se MAb DH2 (anti-GM3). Analisando-se os carboidratos do CMH por cromatografia gasosa acoplado a espectrômetro de massa constatou-se que a mucosa normal expressa glucosilceramida e o CEC glucosilceramida e galactosilceramida. CONCLUSÃO: O aumento de GSLs no tecido tumoral pode representar alterações dos microdomínios da membrana celular resultantes do processo de transformação maligna, responsáveis por uma maior interação célula-célula e célula-matriz aumentando seu potencial de infiltração e metástase, possibilitando o emprego dos GSLs e de MAbs no diagnóstico e no tratamento do CEC, a exemplo do que ocorre no melanoma.

Glycosphingolipids are integral constituents of cellular membrane, arranged in rafts, and with neoplasic cell anti-social behavior, like uncontrolled cell growth, invasiveness, and metastatic potential. AIM: However, there are few studies about glycosphingolipids (GSL) expression in squamous cell carcinoma (SCC). Since GSL are known to be tumor-associated markers we decided to perform a prospective study on the GSL profiles of SCC. METHOD: Specimens of 33 SCC and normal mucosa were obtained and GSLs were extracted and purified by reverse-phase chromatography on C18 column and alkaline hydrolysis in methanol. GSLs were quantified using densitometry of orcinol-stained HPTLC plates. RESULT: A significant increase of GSLs in SCC (3.57æg/mg) was observed as compared to normal mucosa (1.92æg/mg). In SCC, an increase of 2 to 3 times in the amounts of CDH, CTH, Globoside, and GM3 was observed in comparison to normal mucosa. The identification of GM3 as well as its increased expression in SCC was confirmed unequivocally by HPTLC immunostaining and indirect immunofluorescence using MAb DH2 (anti-GM3). BY analyzing SCC and normal mucosa CMHs by GC/MS, normal mucosa expresses only glucosylceramide whereas SCC cells express both glucosylceramide and galactosylceramide. CONCLUSION: The increase in the amount of GSLs in tumor tissue may represent changes of cell membrane microdomains resulting from the malignant transformation process, which is responsible for greater cell-cell or cell-matrix interaction thereby increasing their potential for infiltration and metastasis.

Overexpression of Fos-related antigen-1 in head and neck squamous cell carcinoma.

The activating protein-1 (AP-1) family of transcription factors has been implicated in the control of proliferation and differentiation of keratinocytes, but its role in malignant transformation is not clear. The aim of this study is to assess the pattern of mRNA expression of jun-fos AP-1 family members in 45 samples of head and neck squamous cell carcinomas (HNSCC) and matched adjacent mucosa by means of Northern blot analysis. Transcripts of all family members were identified, except for JunB that was detected only by means of reverse transcription polymerase chain reaction. Neither c-Fos nor JunD or FosB mRNA differed between tumours and normal tissues. We observed a strong Fos-related antigen-1 (Fra-1) and Fra-2 expression, but only Fra-1 mRNA densitometric values were higher in tumour, compared to normal adjacent mucosa (t-test, P = 0.006). A direct relationship between the positive expression of Fra-1 mRNA, above tumour median, was associated with the presence of compromised lymph nodes (Fischer exact test, P = 0.006). In addition, Fra-1 protein staining was assessed in a collection of 180 tumours and 29 histologically normal samples adjacent to tumours in a tissue array. Weak reactivity, restricted to the basal cell layer, was detected in 79% of tumour adjacent normal tissues, opposed to the intense reactivity of cancer tissues. In the subgroup of oral cancers, we have observed a shift in Fra-1 immunoreactivity, as long as the number of patients in each category, cytoplasmic or nuclear/cytoplasmic staining, was analysed (Fischer exact test, P = 0.0005). Thus, Fra-1 gene induction and accumulation of Fra-1 protein may contribute to the neoplastic phenotype in HNSCC.

Perioperative frozen section examination in parotid gland tumors

CONTEXT: The minimal recommended surgical approach to parotid tumors is partial parotidectomy with resection of the superficial lobe of the gland. Histologic diagnosis prior to surgery is not possible, as incisional biopsies are contraindicated due to the possibility of facial nerve injury or incomplete tumor resection. Thus, the biopsies tend to be perioperative. OBJECTIVE: To compare the results of frozen section examination with the definitive pathological diagnosis. DESIGN: Accuracy study by retrospective analysis. SETTING: Head and Neck Surgery Service of Heliópolis Hospital, São Paulo, Brazil. SAMPLE: 153 cases of parotid gland tumors treated between 1977 and 1994. DIAGNOSTIC TEST: Frozen section and pathological diagnosis. MAIN MEASUREMENTS: Sensibility and specificity of the frozen section examination. RESULTS: Frozen section study diagnosed 19 (12.4 percent) malignant and 127 (83.7 percent) benign tumors. Sensitivity of the frozen sections for malignancy was 61.5 percent (95 percent CI 54 to 69 percent) and specificity was 98 percent (95 percewnt CI 94 to 100 percent), and this result is comparable to the literature. CONCLUSIONS: We consider that frozen section examination for salivary gland tumors is not sufficient on its own for deciding on the best management. Their interpretation must be correlated with clinical and intraoperative findings, in association with the surgeon's experience

Relato de um caso: doença de Madelung / A case report: madelung disease

Relatamos um caso de doença de Madelung, uma rara enfermidade caracterizada por acúmulo de gordura difuso e simétrico em regiäo cervical podendo estar associado à deposiçäo de tecido adiposo simetricamente em outras regiöes. A lipomatose benigna simétrica, como também é chamada, acomete principalmente homens brancos, de origem mediterrânea, entre 30 e 60 anos, e apresenta associaçäo com etilismo crônico. Outras doenças que podem estar relacionadas a essa enfermidade säo: hiperuricemia, hiperlipidemia, intolerância à glicose, acidose tubular renal, polineuropatia e hepatopatia. Existem algumas propostas de tratemento clínico, porém sem sucesso. O tratamento de escolha é o cirurgico