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Head and neck squamous cell carcinoma (HNSCC) is well known as a serious health problem worldwide, especially in low-income countries or those with limited resources, such as most countries in Latin America. International guidelines cannot always be applied to a population from a large region with specific conditions. This study established a Latin American guideline for care of patients with head and neck cancer and presented evidence of HNSCC management considering availability and oncologic benefit. A panel composed of 41 head and neck cancer experts systematically worked according to a modified Delphi process on (1) document compilation of evidence-based answers to different questions contextualized by resource availability and oncologic benefit regarding Latin America (region of limited resources and/or without access to all necessary health care system infrastructure), (2) revision of the answers and the classification of levels of evidence and degrees of recommendations of all recommendations, (3) validation of the consensus through two rounds of online surveys, and (4) manuscript composition. The consensus consists of 12 sections: Head and neck cancer staging, Histopathologic evaluation of head and neck cancer, Head and neck surgery-oral cavity, Clinical oncology-oral cavity, Head and neck surgery-oropharynx, Clinical oncology-oropharynx, Head and neck surgery-larynx, Head and neck surgery-larynx/hypopharynx, Clinical oncology-larynx/hypopharynx, Clinical oncology-recurrent and metastatic head and neck cancer, Head and neck surgery-reconstruction and rehabilitation, and Radiation therapy. The present consensus established 48 recommendations on HNSCC patient care considering the availability of resources and focusing on oncologic benefit. These recommendations could also be used to formulate strategies in other regions like Latin America countries.

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Differentiated thyroid carcinoma (DTC) accounts for most cases of thyroid cancer, and the heterogeneity of DTC requires that management decisions be taken by a multidisciplinary team involving endocrinologists, head and neck surgeons, nuclear medicine physicians, pathologists, radiologists, radiation oncologists, and medical oncologists. It is important for nonspecialists to recognize and refer patients with DTC who will benefit from a specialized approach. Recent advances in knowledge and changes in management of DTC call for the need to raise awareness on the part of these nonspecialist physicians, including general endocrinologists and medical oncologists at large. We provide an overview of diagnostic and therapeutic principles in DTC, especially those that bear direct implication on day-to-day management of these patients by generalists. Patients with DTC may be broadly categorized as having localized, locally persistent/recurrent, or metastatic disease. Current recommendations for DTC include a three-tiered system that classifies patients with localized disease into low, intermediate, or high risk of persistent or recurrent disease. Risk stratification should be performed at baseline and repeated on an ongoing basis, depending on clinical evolution. One of the overarching goals in the management of DTC is the need to personalize treatment by tailoring its modality and intensity according to ongoing prognostic stratification, evolving knowledge about the disease, and patient characteristics and preference. In metastatic disease that is refractory to radioactive iodine, thyroid tumors are being reclassified into molecular subtypes that better reflect their biological properties and for which molecular alterations can be targeted with specific agents.

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ABSTRACT Differentiated thyroid carcinoma (DTC) accounts for most cases of thyroid cancer, and the heterogeneity of DTC requires that management decisions be taken by a multidisciplinary team involving endocrinologists, head and neck surgeons, nuclear medicine physicians, pathologists, radiologists, radiation oncologists, and medical oncologists. It is important for nonspecialists to recognize and refer patients with DTC who will benefit from a specialized approach. Recent advances in knowledge and changes in management of DTC call for the need to raise awareness on the part of these nonspecialist physicians, including general endocrinologists and medical oncologists at large. We provide an overview of diagnostic and therapeutic principles in DTC, especially those that bear direct implication on day-to-day management of these patients by generalists. Patients with DTC may be broadly categorized as having localized, locally persistent/recurrent, or metastatic disease. Current recommendations for DTC include a three-tiered system that classifies patients with localized disease into low, intermediate, or high risk of persistent or recurrent disease. Risk stratification should be performed at baseline and repeated on an ongoing basis, depending on clinical evolution. One of the overarching goals in the management of DTC is the need to personalize treatment by tailoring its modality and intensity according to ongoing prognostic stratification, evolving knowledge about the disease, and patient characteristics and preference. In metastatic disease that is refractory to radioactive iodine, thyroid tumors are being reclassified into molecular subtypes that better reflect their biological properties and for which molecular alterations can be targeted with specific agents.

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O tratamento metronômico consiste na administração regular e contínua de quimioterápicos em baixa dose, preferivelmente via oral, sem pausas prolongadas, com objetivo de bloquear a proliferação tumoral. Este tratamento tem sido utilizado para uma série de tumores e nos últimos anos notou-se aumento da utilização em estudos clínicos, principalmente no cenário paliativo. Objetivo: Realizar uma revisão narrativa acerca do tema quimioterapia metronômica em tumores sólidos, nos seus aspectos de definição, racional biológico, indicação clínica, marcadores preditivos e prognósticos. Metodologia: Foi realizada uma pesquisa na base de dados PUBMED, maior base de dados de conteúdo médico, onde foram encontrados 575 artigos, dos quais 46 artigos se adequavam aos critérios de seleção (artigos em inglês publicados no período compreendido entre 2015 a 2020), dentre eles 32 artigos de revisão, 1 metanálise, 2 retrospectivos, 9 prospectivos e 2 descritivos. E, após análise pormenorizada, 529 artigos foram excluídos devido aos critérios de exclusão: artigos em outras línguas que não inglês e a utilização apenas de anticorpo, imunoterapia ou terapia alvo molecular sem quimioterapia associados. Resultados: A partir da análise dos 46 artigos, foram encontrados descrições acerca dos aspectos conceituais, teorias metronômicas, efeito angiogênico, imunológico e quiescência tumoral, efeito 4 "D" e indicação clínica, avaliação de eficácia, segurança, marcadores, precisão e custo efetividade. Conclusão: Verificou-se que evidências clínicas e pré-clínicas suportam o uso de quimioterapia metronômica como uma alternativa ao tratamento oncológico padrão em cenário de acesso restrito a novas drogas, tais como: terapia alvo ou imunoterapia, sendo a principal característica sua baixa toxicidade, acessibilidade, disponibilidade de drogas para administração oral e alta atividade anti-angiogênica, além de outros efeitos diretos e indiretos, os quais se traduzem em benefício clínico

Metronomic treatment consists of regular and continuous administration of low-dose chemotherapy, preferably orally, without prolonged pauses, with the aim of blocking tumor proliferation. This treatment has been used for a number of tumors and, in recent years, there has been an increase in its use in clinical studies, especially in the palliative setting. Objective: To carry out a narrative review on the topic metronomic chemotherapy in solid tumors, in its aspects of definition, biological rationale, clinical indication, predictive and prognostic markers. Methodology: A search was carried out in the PUBMED database, the largest database of medical content, where 575 articles were found, of which 46 articles fit the selection criteria (articles in English published between 2015 and 2020), among them 32 review articles, 1 meta-analysis, 2 retrospective, 9 prospective and 2 descriptive. And, after a detailed analysis, 529 articles were excluded, due to the exclusion criteria: articles in languages other than English and the use of antibody alone, immunotherapy or molecular targeted therapy without associated chemotherapy. Results: From the analysis of the 46 articles, descriptions were found about the conceptual aspects, metronomic theories, angiogenic, immunological and tumor quiescence effects, 4 "D" effect and clinical indication, evaluation of efficacy, safety, markers, precision and cost effectiveness . Conclusion: It was found that clinical and preclinical evidence support the use of metronomic chemotherapy as an alternative to standard cancer treatment in a scenario of restricted access to new drugs, such as targeted therapy or immunotherapy, the main feature being its low toxicity, accessibility, availability of drugs for oral administration and high anti-angiogenic activity, in addition to other direct and indirect effects, which translate into clinical benefit

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Changes in metabolism are mechanisms that are largely implicated in the development, progression, and metastasis of head and neck squamous cell carcinoma (HNSCC) and also in resistance to different anticancer therapies. Identification of biomarkers for differentiation between cancerous and normal epithelium, treatment design and prognosis remain a vital issue in the field of head and neck cancer. The present study analyzed the main biochemical changes that occur in HNSCC tumors by through mechanisms involving oxidative stress. The release of substances reactive to thiobarbituric acid was significantly lower in HNSCC tumor tissue as compared to healthy tissue. The assays related to the lipid profile assays showed changes in membrane biophysics of tumor cells due to an increase in total phospholipids and total cholesterol, as well as an increased activity and expression of the α1 subunit of Na, K-ATPase, which is fundamental in the process of carcinogenesis. The modulation of the antioxidant system was also affected, with a decrease in the catalytic activity of the enzymes superoxide dismutase (SOD) and glutathione peroxidase (GPx), as well as a reduction of glutathione (GSH) content and an increase in H2O2 content. A reduction in catalase (CAT) activity was observed. The data presented here are in accordance with important findings described by us in a previous study, involving the same individuals, but with a focus on the damage generated in red blood cells, resulting from tumor installation. Therefore, it was possible to conclude that the biochemical alterations found in HNSCC cells are fundamental for transformation and maintenance of the tumor cell and once it is installed, it is also capable of generating injuries in the patients' red blood cells. Our data demonstrate that this could be a promising biomarker for HNSCC.

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Mucositis is one of the more frequent and costly adverse events following cancer treatment. To evaluate and report the direct economic outcomes associated with the management of mucositis across several cancer treatments we conducted a systematic review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Scopus, MEDLINE/PubMed, and Embase were searched electronically and a total of 37 relevant studies were included. The costs attributable to mucositis in the hematopoietic stem cell transplantation setting ranged from 1124,47 US dollars (USD) to 299 214,14 USD per patient. The radiotherapy/chemoradiotherapy/radiotherapy plus molecular targeted therapy accounted for mucositis costs that ranged from 51,23 USD to 33 560,58 USD per patient. Costs for mucositis in the chemotherapy setting ranged from 4,18 USD to 31 963,64 USD per patient. When the cancer treatment was not specified, costs of mucositis ranged from 565,85 USD to as high as 20 279, 12 USD per patient. Mucositis costs from multimodal therapy ranged from 12,42 USD to 5670,46 USD per patient. The molecular targeted therapy setting included only one study and depending on the healthcare providers' perspective of each country evaluated, mucositis' costs ranged from 45,78 USD to 3484,91 USD per patient. Mucositis is associated with increased resource use, consultations, hospitalizations and extended hospitalizations, leading to a substantial incremental cost that exacerbates the economic burden on the patient, health plan and health system across several cancer treatments and diagnosis. More studies with a prospective evaluation of the economic costs associated with mucositis management are needed.

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OBJECTIVE: The aim of this study was to estimate the frequency of oral leukoplakia and oral erythroplakia in young patients. STUDY DESIGN: The systematic review was based on the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines and performed in the following electronic databases: PubMed, Scopus, and Embase. The studies included were cross-sectional, cohort, and diagnostic, which provided with clinical and microscopic data of patients younger than 40 years. The Critical Appraisal Checklist for Prevalence Studies from the Joanna Briggs Institute and the Quality Assessment Tool for Diagnostic Accuracy Studies were used to assess the risk of bias. RESULTS: Five studies met eligibility criteria and were included. The total number of patients from the studies was 1246, of which 115 were young patients (9.2%) with oral leukoplakia as the only oral potentially malignant disorder reported. Oral epithelial dysplasia was identified in 40 cases (34.7%), of which 8 (6.9%) presented malignant transformation. CONCLUSIONS: The frequency of oral leukoplakia is low in young patients. Observational studies are necessary for understanding oral leukoplakia and other oral potentially malignant disorders in younger patients.

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Head and neck squamous cell carcinoma (HNSCC) is a heterogeneous and complex disease, both from a clinical and molecular point of view. The prolonged use of alcohol and tobacco, along with the release of tumor secretions can modulate blood cells, such as erythrocytes. Here, this study was conducted with 24 patients diagnosed with HNSCC and an equal number of healthy individuals are matched by age and gender. The levels of lipid peroxidation were measured using the individual plasma, while for lipid concentrations, identification and quantification Na, K-ATPase activity and osmotic fragility, the red blood cell concentrate were used. The release of TBARS was significantly higher in patients with HNSCC. The lipid profile assays demonstrated a rearrangement of the erythrocyte membrane due to a decrease in total phospholipids and phosphatidylethanolamine followed by an increase in total cholesterol and phosphatidylcholine. Na, K-ATPase activity also increased. Erythrocytes were more fragile in patients with HNSCC than in health individuals. Therefore, the membrane of erythrocytes were rearranged and Na, K-ATPase function altered in the HNSCC patients. Our findings suggests that the alcohol, tobacco and tumor secretion modulate in a specific manner that the erythrocytes membranes of these patients making this system a potential tool for HNSCC biomarker of tumor progression.

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Abstract Introduction Coronavirus disease 2019 (COVID-19) is an acute infection caused by the new coronavirus (SARS-CoV-2) and it is highly transmissible, especially through respiratory droplets. To prepare the health system for the care of these patients also led to a restriction in the activity of several medical specialties. Physicians who work with patients affected by diseases of the head and neck region constitute one of the populations most vulnerable to COVID-19 and also most affected by the interruption of their professional activities. Objective The aim of the present study was to assess the impact of the COVID-19 pandemic on the practice of head and neck surgeons and otorhinolaryngologists in Brazil. Methods An anonymous online survey of voluntary participation was applied, containing 30 questions regarding demographic aspects, availability of personal protective equipment (PPE), and impact on the routine of head and neck surgeons and otorhinolaryngologists, as well as clinical oncologists and radiation oncologists who work with head and neck diseases. Results Seven hundred and twenty-nine answers were received in a period of 4 days, ∼ 40 days after the 1st confirmed case in Brazil. With professionals working in public and private services, there was a high level of concerns with the disease and its consequences, limited availability of PPE and a significant decrease in the volume of specialized medical care. Conclusion The study demonstrated a direct impact of the COVID-19 pandemic on the clinical practice of specialties related to the treatment of patients with diseases of the head and neck region already in the beginning of the illness management in Brazil.

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Introduction Coronavirus disease 2019 (COVID-19) is an acute infection caused by the new coronavirus (SARS-CoV-2) and it is highly transmissible, especially through respiratory droplets. To prepare the health system for the care of these patients also led to a restriction in the activity of several medical specialties. Physicians who work with patients affected by diseases of the head and neck region constitute one of the populations most vulnerable to COVID-19 and also most affected by the interruption of their professional activities. Objective The aim of the present study was to assess the impact of the COVID-19 pandemic on the practice of head and neck surgeons and otorhinolaryngologists in Brazil. Methods An anonymous online survey of voluntary participation was applied, containing 30 questions regarding demographic aspects, availability of personal protective equipment (PPE), and impact on the routine of head and neck surgeons and otorhinolaryngologists, as well as clinical oncologists and radiation oncologists who work with head and neck diseases. Results Seven hundred and twenty-nine answers were received in a period of 4 days, ∼ 40 days after the 1 st confirmed case in Brazil. With professionals working in public and private services, there was a high level of concerns with the disease and its consequences, limited availability of PPE and a significant decrease in the volume of specialized medical care. Conclusion The study demonstrated a direct impact of the COVID-19 pandemic on the clinical practice of specialties related to the treatment of patients with diseases of the head and neck region already in the beginning of the illness management in Brazil.

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OBJECTIVE: The aim of this study was to evaluate the immunohistochemical expressions of PD1, CD4+, and CD8+ in premalignant lesions (OPML) that were transformed into oral squamous cell carcinoma OSCC (OPML-OSCC), in OSCC and also in premalignant lesions that were not transformed into OSCC (OPML-NOSSC). MATERIALS AND METHODS: Retrospective analyses were performed in order to verify the demographic characteristics of the patients. CD4, CD8, and PD1 IMH studies were carried out on OPML and OSCC samples from 11 patients with OPML-OSCC and OPML, together with samples from 14 patients with OPML-NOSCC. The differences between OPML-OSCC and OPML-NOSCC were analyzed. RESULTS: Non-homogenous leukoplakia, together with the related oral subsite, and the lack of an exposure to tobacco, were all associated with malignant transformations. There were no statistical differences in the PD1 expression and the CD4+ cells in OPML-OSCC and OPML-NOSCC. A significant increment in the CD8+ cells was noted in the OPML that evolved into carcinomas when compared with OPML-NOSCC (p = 0.05), whereas there were higher CD8+ cells levels in the carcinomas when compared with the OPML that evolved into carcinomas (p = 0.027). CONCLUSIONS: CD8+ cells infiltrate more in OPML-NOSCC than in OPML-OSCC. Carcinoma is more infiltrated by CD8+ cells than its associated OPML. CLINICAL RELEVANCE: Understanding immunological factors associated with malignant transformation of oral premalignant lesions can open a new way to treat this disease.

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Introdução: O câncer de sítio primário desconhecido caracteriza-se pela presença de doença metastática ao diagnóstico, sem localização do tumor primário. Objetivo: Conhecer o perfil dos pacientes com diagnóstico de câncer de sítio primário desconhecido em um centro de oncologia terciário. Material e método: Estudo retrospectivo e descritivo no qual foram analisados os prontuários dos pacientes com câncer de sítio primário oculto entre 2002 e 2012. Resultados: Entre os 68 prontuários analisados, observou-se que o adenocarcinoma é o tipo histológico mais frequente (39,71%) seguido pelo carcinoma espinocelular (29,41%). Os sítios de metástases mais recorrentes foram a região cervical (38,23%), fígado (20,58%) e peritônio (16,71%). A imuno-histoquímica foi realizada em 44,12%, os pacientes com acometimento cervical não se beneficiaram da elucidação diagnóstica por este meio, devido à falta de marcadores específi cos para este sítio. Em relação ao tratamento, 60,29% dos pacientes foram submetidos a alguma modalidade terapêutica, sendo a quimioterapia a mais comum, onde a cisplatina foi o antineoplásico mais utilizado de forma isolada (11,76%) e o esquema etoposídeo e cisplatina mais realizado em combinação (7,35%). Conclusão: O estudo está em consonância com os dados da literatura sobre o perfil destes pacientes; entretanto, apesar dos avanços nas técnicas diagnósticas, esta síndrome ainda representa um desafio na prática oncológica.

Introduction: Cancer is characterized by the presence of metastatic disease at diagnosis, without location of the primary tumor. Aim: To know the profile of patients diagnosed with cancer of unknown primary site in a tertiary cancer center. Methods: A retrospective study in which the medical records of patients with cancer of unknown primary site were analyzed between 2002 and 2012. Results: From the 68 charts analyzed adenocarcinoma was found to be the most common histological type (39.71 %), followed by squamous-cell carcinoma (29.41%). The most frequent metastasis sites were the cervical region (38.23%), liver (20.58%) and peritoneum (16.71%). Immunohistochemistry was performed on 44.12%, patients with cervical involvement did not benefi t from such diagnostic clarification due to lack of specific markers for this site. Regarding treatment, 60.29% of patients underwent some form of therapy, the most common being chemotherapy, where cisplatin was the most often antineoplastic used alone (11.76%) and etoposide plus cisplatin the most often used regimen used in combination (7.35%). Conclusion: The study is consistent with published data on the profile of these patients. Despite the advances in diagnostic techniques, however, this syndrome is still a challenge in oncology practice.

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The Actinomyces sp has been linked to osteoradionecrosis of the jaw. The identification of these bacteria on histopathological findings confers a determining factor of poor prognosis and is related to difficulties of local control of bone necrosis and risk of recurrent infections. The treatment is complicated due to insidious growth pattern of Actinomyces sp. The methods for diagnosis and therapeutic approaches constitute challenges that underscore the need for understanding the risk factors for infection and knowledge about clinical conditions associated with this pathology. The objective of this study is to report two cases of cancer patients suffering from an osteoradionecrosis infection by Actinomyces sp, to describe approaches and discuss therapeutic options in the light of the current literature.

O Actinomyces sp tem sido associado a osteorradionecrose. A identificação desta bactéria confere um fator determinante de mau prognóstico e está relacionado a dificuldades do controle da necrose óssea local e a risco de infecções recorrentes. O tratamento é complicado devido ao padrão de crescimento insidioso do Actinomyces sp. Os métodos de diagnóstico e as abordagens terapêuticas constituem desafios que reforçam a necessidade de compreender os fatores de risco para a infecção e o conhecimento sobre as condições clínicas associadas a esta patologia. O objetivo deste trabalho é relatar dois casos clínicos de pacientes com câncer que sofrem infecção osteorradionecrose por Actinomyces sp, para descrever as abordagens e discutir as opções terapêuticas à luz da literatura atual.

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AIM: The present study evaluated the expression of α1 and ß1 Na,K-ATPase, as well as the effects of digoxin (DGX) on oral squamous cell carcinomas (OSCCs). PATIENTS AND METHODS: Immunohistochemical expression of α1 and ß1 Na,K-ATPase were evaluated in 60 patients who underwent treatment at the São João de Deus Hospital. SCC-25 viability was assessed by the colorimetric assay. Chi-square or Fisher's exact tests were used to analyze the association of α1 and ß1 Na,K-ATPase expression with the variables. RESULTS: Immunoexpression of α1 and ß1 Na,K-ATPase were observed in 28% and 55% of the tumors, however these proteins were not significant prognostic factors. Tobacco was significantly associated with α1 expression. SCC-25 viability decreased significantly after treatment with 1 µM DGX at 24 h. CONCLUSION: The smoking status of OSCC patients was significantly associated with α1 expression and DGX affected the SCC-25 viability in a dose- and duration-dependent manner.

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O câncer de boca representa um problema de saúde pública devido aos diagnósticos tardios e das taxas de morbimortalidade. Esse estudo avaliou o nível de conhecimento dos odontólogos (23) da atenção primária da rede pública de Divinópolis (MG) sobre o câncer bucal. Empregou-se questionário estruturado e os dados obtidos demonstraram que 39,1% dos entrevistados não sabiam qual o tipo mais comum de câncer de boca; 35% avaliaram seu nível de conhecimento como bom ou ótimo. Fatores de risco apontados: uso do tabaco, antecedentes familiares, uso do álcool e exposição solar. Apenas 13% receberam treinamento para o exame de câncer bucal na graduação. Esses achados reforçam a necessidade de abordagem do tema no período de formação acadêmica e de educação continuada.

Oral cancer represents a major public health problem due to high rates of late diagnoses and significant morbidity and mortality rates. This study assessed the level of knowledge of active dentists (23) in primary care in public health at Divinópolis (MG) on oral cancer. A structured questionnaire was used. The data showed that 39.1% of respondents didn`t know what the most common type of oral cancer, 35% rated their level of knowledge as good or great. Tobacco use, family history, alcohol use and sun exposure were the most likely risk factors mentioned. Only 13% received training for oral cancer exam on graduation. These findings reinforce the need for a greater approach regarding the theme during academic training and continuing education.

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O presente relato de caso refere-se ao carcinomaneuroendócrino de pequenas células de laringe acometendouma mulher de 52 anos. Este carcinoma é umaneoplasia altamente maligna com metástases frequentese taxa de sobrevida baixa. Depois dos carcinomasespinocelulares, os tumores de laringe mais frequentessão os neuroendócrinos, que podem ser derivados decélulas neurais ou epiteliais. Os tumores neuroendócrinosderivados de epitélio podem ser classificados emquatro grupos patológicos bem definidos: tumor carcinoide,tumor carcinoide atípico, carcinoma neuroendócrinode pequenas células e carcinoma neuroendócrinode células grandes. Os carcinomas neuroendócrinos têmmorfologia distinta, entretanto apresentam perfil imunohistoquímicomarcado por algumas combinações depositividade para citoqueratina, cromogranina, sinaptofisina,CD56, CD57, enolase, serotonina, somatostatinae bombesina. Esses tumores da laringe apresentam umgrande espectro de evolução clínica, dependente dosubtipo histológico, que influencia significativamente oplanejamento de todo o tratamento.

This case report refers to small cell neuroendocrinecarcinoma of the larynx affecting a 52-year-old female.This is a highly malignant neoplasm with frequentmetastases and a lower survival rate. After squamouscarcinomas, the most frequent tumors of the larynx arethe neuroendocrine, these tumors can be derived fromneural or epithelial cells. Neuroendocrine tumors derivedfrom epithelium can be classified into four pathologicalcategories defined: carcinoid tumor, atypical carcinoidtumor, small cell neuroendocrine carcinoma andlarge cell neuroendocrine carcinoma. It is known thatdespite of having distinct morphology, neuroendocrinecarcinomas have immunohistochemical profile markedby some combination of positive for cytokeratin, chromogranin,synaptophysin, CD56, CD57, enolase, serotonin,somatostatin and bombesin. These laryngeal tumorsshow a broad spectrum of clinical, dependent onthe histological subtype, which influences the planningof the whole treatment.