Abstract Objective: The aim of the present study was to analyze the prognostic relationship of weight loss and preoperative hematological indexes in patients surgically treated for pT4a squamous cell carcinoma of the oral cavity. Methods: A retrospective cohort study. Results: Percent weight loss greater than 10% was identified in 49 patients (28.2%), and any weight loss in relation to the usual weight occurred in 140 patients (78.7%). Percent weight loss greater than 10% (HR = 1.679), Red cell distribution width (RDW) values greater than 14.3% (HR = 2.210) and extracapsular spread (HR = 1.677) were independent variables associated with risk of death. Conclusion: Patients with advanced squamous cell carcinoma of the oral cavity present significant weight loss and as significantly immunocompromised. Increased values of RDW and higher percentages of weight loss in relation to the individual’s usual weight, together with extracapsular spread of metastatic lymph nodes, were risk factors for lower survival, regardless of other clinical and anatomopathological characteristics. Level of evidence: 3.

Abstract Introduction Treatment of stage III laryngeal cancer suffered a major paradigm change with surgery being substituted by radiation therapy with chemotherapy. Objective To evaluate the oncological outcome of different treatment modalities for stage III laryngeal cancer using a population database. Methods A population database representing patients treated in the state of São Paulo, Brazil, was analyzed. Demographic, clinical and treatment variables were included, and the outcomes of interest were disease-specific and overall survival. Propensity score with nearest neighbor matching was used to compensate for imbalances in treatment groups. Results We retrieved data from 1,804 patients. In multivariate analysis, age, female gender, payment source, clinical N stage (cN) stages, and treatment modality were significant for disease-specific and overall survival. Patients submitted to surgery treatment had a significantly better disease-specific (p < 0.001) and overall survival (p <0.001) compared with chemoradiation. Propensity score matching was based on cN stage, gender, age, topography, and payment modality, and allowed the pairing of 685 patients from each treatment modality. There was a significant difference in disease-specific survival favoring surgery-based treatment (p = 0.017). Conclusion The treatment choice has a significant impact on survival in patients with stage III laryngeal cancer with surgery-based treatment being superior to chemoradiotherapy (CRT).

Resumo Introdução: O carcinoma papilífero de tireoide é a neoplasia endócrina mais frequente e sua incidência triplicou nos últimos 35 anos. Embora o carcinoma papilífero de tireoide tenha um bom prognóstico, 1% a 30% dos pacientes desenvolvem recorrência e metástase. Algumas características clínicas e genéticas estão associadas a um pior prognóstico. A mutação mais frequente é a BRAF p.V600E, a qual tem sido associada a muitas características clínicas de pior prognóstico. No entanto, muitos estudos apresentam resultados controversos, sem qualquer associação entre a mutação em BRAF e características clinicopatológicas de pior prognóstico. Objetivo: Uma vez que o valor prognóstico das mutações em BRAF permanece controverso, investigar a importância dessa mutação em decisões terapêuticas para o carcinoma papilífero de tireoide. Método: Foi avaliada a associação da mutação em BRAF com características de pior prognóstico em 85 pacientes com carcinoma papilífero de tireoide acima de 45 anos tratados no A.C. Camargo Cancer Center, de 1980 a 2007. A mutação em BRAF foi avaliada por pirossequenciamento. A análise estatística foi feita com o software SPSS. Resultados: A média de idade dos pacientes foi de 54 anos (variação de 45 - 77), 73 eram mulheres (85,8%) e 12 eram homens (14,2%). Entre eles, 39 casos (45,9%) apresentaram extensão extratireoidiana e 11, doença recorrente. A mutação em BRAF foi detectada em 57 (67%) pacientes. Não foi observada associação significante entre mutação em BRAF e sexo (p = 0,743), idade (p = 0,236), estágio N (p = 0,423), infiltração vascular e perineural (p = 0,085) ou multi-focalidade (p = 1,0). Apesar de não apresentar associação estatística, a maioria dos pacientes com doença recorrente foi positiva para BRAF (9 em 11) (p = 0,325). Os pacientes afetados pela mutação em BRAF estão associados a tumores maiores do que 1 cm (p = 0,034) e com extensão extratireoidiana (p = 0,033). Conclusão: Embora a mutação em BRAF seja amplamente avaliada, não há dados consistentes que demonstrem uma melhor sobrevida ou benefício clínico ao incorporá-la à decisão terapêutica para o câncer de tireoide.

Abstract Introduction: Papillary thyroid carcinoma is the most frequent endocrine neoplasia and its incidence has tripled over the past 35years. Although papillary thyroid carcinoma carries a good prognosis, 10%–30% of patients still develop recurrence and metastasis. Some clinical and genetic features are associated with worse prognosis. The most frequent mutation is the BRAF p.V600E, which has been associated with many clinical features of poor prognosis. However, many studies have produced controversial results without any association between BRAF mutation and clinicopathological features of poor prognosis. Objective: Since the prognostic value of BRAF mutations remains controversial, this study aims to investigate the importance of this mutation in therapeutic decisions for papillary thyroid carcinoma. Methods: Therefore, we evaluated whether the presence of BRAF mutation is associated with features of poor prognosis in 85 patients with papillary thyroid carcinoma older than 45years treated at A.C. Camargo Cancer Center, from 1980 to 2007. BRAF mutation was evaluated by pyrosequencing. Statistical analysis was performed using SPSS. Results: The mean age of patients was 54 years (range: 45 - 77 years), 73 were women (85.8%) and 12 were men (14.2%). Among them, 39 cases (45.9%) presented extrathyroidal extension and 11 cases had recurrent disease. BRAF mutation was detected in 57 (67%) patients. No significant association was observed between BRAF mutation and gender (p =0.743), age (p = 0.236), N-stage (p =0.423), vascular and perineural infiltration (p =0.085 or multifocality (p = 1.0). Although not statistically significant, the majority of patients with recurrent disease were BRAF positive (9 out of 11) (p =0.325). Patients affected by BRAF mutation are associated with tumors larger than 1 cm (p =0.034) and with extrathyroidal extension (p =0.033). Conclusion: Although BRAF testing is widely available, there are no consistent data to support improvement in outcomes from incorporating it into therapeutic decision for thyroid cancer.

Resumo Introdução O carcinoma epidermoide de laringe é o segundo mais prevalente entre os tumores de cabeça e pescoço e o tratamento dos pacientes com doença em estádio I ou II pode ser feito com cirurgia ou radioterapia. Estudos populacionais nacionais que descrevem os resultados terapêuticos e compararam essas modalidades são poucos frequentes, mas podem ser muito importantes para orientar diretrizes de tratamento. Objetivo Avaliar os resultados de sobrevida dos pacientes com carcinoma epidermoide de laringe em estádios clínicos I ou II de acordo com as principais modalidades terapêuticas usadas. Método Estudo transversal de base populacional com a base de dados da Fundação Oncocentro de São Paulo de janeiro de 2000 a março de 2019. Os critérios de inclusão foram pacientes com carcinoma epidermoide de laringe em estádios clínicos cT1-2N0. Para compensar pela alocação não randômica dos pacientes e pelo desequilíbrio entre variáveis confundidoras entre os grupos, usamos a metodologia do escore de propensão. Resultados Preencheram os critérios de inclusão 3.786 pacientes. Em relação ao estádio cT, houve 2.171 pacientes (57,3%) com tumores cT1. Os pacientes do sistema único de saúde (SUS) apresentaram um maior tempo entre o diagnóstico e o tratamento (p < 0,001). A análise por escore de propensão mostrou que os pacientes submetidos a cirurgia apresentaram uma tendência de melhor sobrevida doença específica (p = 0,012). Comparando-se radioterapia isolada versus combinação com radioquimioterapia, o tratamento isolado demonstrou tendência a melhor taxa de sobrevida (p< 0,001). Conclusão A análise por escore de propensão identificou melhores resultados de sobrevida doença específica em pacientes com carcinoma epidermoide de laringe estádios clínicos I e II tratados por cirurgia quando comparados a radioterapia.

Abstract Introduction Laryngeal squamous cell carcinoma is the second most prevalent malignancy among head and neck tumors, and the treatment of patients with stage I or II disease can be performed with surgery or radiation therapy. National population studies describing therapeutic results comparing these modalities are unusual, but they can be very important to direct treatment guidelines. Objective To evaluate the survival results of patients with laryngeal squamous cell carcinoma at clinical stages I or II, according to the main therapeutic modalities used. Methods Cross-sectional, population-based study using the database of Fundação Oncocentro de São Paulo from January 2000 to March 2019. Inclusion criteria were patients with laryngeal squamous cell carcinoma in clinical stages cT1-2N0. To compensate for the non-random allocation of patients and the imbalance between confounding variables between groups, we used the propensity score methodology. Results A total of 3786 patients met the inclusion criteria. Regarding the cT stage, there were 2171 patients (57.3%) with cT1 tumors. Patients in the public health system had a longer time between diagnosis and treatment (p< 0.001). The analysis by propensity score showed that patients treated with surgery had a tendency towards better disease-specific survival (p = 0.012). Comparing radiotherapy alone versus its combination with radiochemotherapy, radiotherapy alone showed a tendency towards a better survival rate (p< 0.001). Conclusion Analysis by propensity score identified better results for disease-specific survival in patients with laryngeal squamous cell carcinoma at clinical stages I and II treated by surgery when compared to radiotherapy.

SUMMARY We report a rare case of Cushing’s syndrome in a 37-year-old female who initially presented with localized acinic cell carcinoma of the parotid gland. In January 2014, she underwent a right parotidectomy with facial nerve preservation and adjuvant radiotherapy. In August 2018, she presented a histologically-proven local regional relapse. The patient was considered for salvage surgery with facial nerve sacrifice and remained with no evidence of disease. One year later the patient developed pulmonary dissemination and started to gain weight and developed facial plethora and acne on the face and upper trunk. In a physical examination, the patient presented moon face, buffalo hump, acne and stage 2 hypertension. Biochemical evaluation confirmed ACTH-dependent Cushing’s syndrome. IHC for ACTH in the lung biopsy revealed strong positive staining for ACTH confirming a diagnosis of ectopic ACTH secretion by a metastatic parotid acinic cell carcinoma. Ketoconazole (600 mg/d) was started to treat the CS. In addition, as chemotherapy was initiated to treat the metastatic disease. After the fifth cycle of chemotherapy, ketoconazole was suspended and the patient remained in remission of CS for four months, when CS recurred. A unique feature of this case is related to the clinical CS relapse associated with disease progression, which needed prompt treatment with ketoconazole, resulting in a significant improvement in the patient’s condition. Although rare, should be attentive for possible CS features in patients with high-grade salivary gland carcinomas, since the diagnosis of ectopic secretion of ACTH may significantly impact their management and outcomes.

Abstract Dendritic cells (DCs) are specialized antigen-presenting cells that play a critical role in the immune response against human papillomavirus (HPV) infection, and represent a therapeutic target in cancer. Objective: To identify and quantify DCs in tonsillar squamous cell carcinoma (TSCC) under the influence of HPV infection. Methodology: CD1a and CD83 antibodies were used to identify immature dendritic cells and mature dendritic cells by immunohistochemistry in 33 primary TSCC and 10 normal tonsils (NTs), respectively. For the TSCC samples, the number of DCs per area was evaluated in the intra- and peritumoral compartments. For the NTs, the quantification of DCs was evaluated in the intra- and peritonsillar compartments. HPV detection methods were determined according to the ASCO Clinical Practice Guidelines from the College of American Pathologists Guideline (2018). Results: There were fewer intratumoral CD1a+ DCs in the HPV-positive and HPV-negative TSCC groups than in the NT group (p<0.05). In the peritumoral compartment, there were fewer CD83+ DCs in the HPV-positive and HPV-negative TSCC groups than in the NT group (p<0.001). The quantification of DCs subtypes showed no statistical differences between HPV-positive and HPV-negative TSCC groups (p>0.137). Patients with HPV-positive TSCC had significantly better overall survival rate than those with HPV-negative TSCC (p=0.004). Conclusion: Tumor activity contributes to DC depletion regardless of intralesional HPV positivity. An improved prognosis has been reported in patients with HPV-positive TSCC.

Abstract Objective To investigate Incidental Thyroid Carcinoma (ITC) by comparing the results of Fine Needle Aspiration Biopsy (FNAB) cytology and the postoperative pathological findings. Methods Data of 1479 patients who underwent total thyroidectomy were retrieved. Three hundred eighty-six patients were excluded due to insufficient data. Each surgical specimen studied received two histopathological diagnoses: the local diagnosis ‒ for the same area in which the FNAB was performed; and the final diagnosis, which includes a study of the entire surgical specimen. Results A thousand and ninety-three patients were investigated. FNAB result was malignant in 187 patients, benign in 204, suspicious or indeterminate in 668 cases, and inconclusive in 34 cases. The prevalence of ITC was 15.1%. Most of the ITC in this series was less than 0.5 cm. The incidence of ITC was higher in Bethesda III (17.5% ITC) and IV (19% ITC) than in Bethesda II cases (1.5% false negatives and 9% ITC). Conclusion Although the incidence of false-negative results in Bethesda II nodules is only 1.5%, 9% of these patients had ITC in the thyroid parenchyma outside the nodule that underwent preoperative FNAB. The incidence of ITC in the same scenario was even higher in Bethesda III (17.5%) and Bethesda IV cases (19%). Ultrasonography-guided FNAB is an excellent method for the assessment of thyroid nodules. However, biopsy sites should be carefully selected. Despite the high incidence of incidentalomas, total thyroidectomy should not always be the treatment of choice due to its rare but potentially serious complications. The findings of the present study can assist future clinical decisions towards active surveillance strategies for the management of papillary thyroid carcinoma.

Abstract Introduction The incidence of papillary thyroid microcarcinoma (PTMC) has increased, and its treatment remains controversial. Objective To identify the clinical and pathological factors predictive of tumor recurrence. Methods We retrospectively analyzed 2,538 consecutive patients treated for PTMC, most submitted to total thyroidectomy (98%) followed by radioactive iodine (RAI) ablation (51.7%) at a cancer center from 1996 to 2015. The patients were stratified according to the AmericanThyroid Association (ATA) risk categories (low, intermediate, or high), and the clinicopathological features were evaluated by multivariate Cox regression analysis to identify independent prognostic factors for recurrence. Results After a mean follow-up of 58 months (range: 3 to 236.5 months), tumor recurrence was diagnosed in 63 (2.5%) patients, mostly in the lymph nodes. Distant metastasis occurred in 2 (0.1%) patients. There were no cancer-related deaths. The multivariate analysis showed that age < 55 years (p = 0.049; hazard ratio [HR]: 2.54; 95% confidence interval [95%CI]: 0.95 to 0.99), multifocality (p = 0.032; HR: 1.76; 95% CI: 1.05 to 2.96), and the presence of lymph-node metastasis (p < 0.001; HR: 3.69; 95% CI: 2.07–6.57) were independent risk factors for recurrence. Recurrence was observed in 29 (1.5%) out of 1,940 low-risk patients, 32 (5.4%) out of 590 intermediate-risk patients, and in 2 (25%) out of 8 high-risk patients. Conclusions The prognosis of PTMC is excellent, favoring a conservative treatment for most patients. Age <55 years, multifocality, and node metastasis at diagnosis, as well the ATA staging system effectively predict the risk of recurrence. The presence of these risk factors can help identify patients who should be considered for more aggressive management and more frequent follow-up.

Abstract Introduction Postoperative neck hematoma (PNH) is an uncommon but potentially-lethal complication of thyroid surgery. Objective To identify the risk factors for postthyroidectomy hematoma requiring reoperation, the timing, the source of the bleeding, the related respiratory distress requiring tracheotomy, and the late outcomes. Methods We retrospectively analyzed the records of 5,900 consecutive patients submitted to surgery for thyroid diseases at a single institution. Results In total, PNH occurred in 62 (1.1%) patients. Most cases of bleeding occurred within the first 6 hours after thyroidectomy, but 12.5% of the hematomas were observed after 24 hours. Obvious bleeding points were detected in 58.1% of the patients during the reoperation, with inferior thyroid artery branches and superior thyroid vessels being the most frequent bleeding sources. Only two patients required urgent tracheostomy. There were no hematoma-related deaths. Permanent hypoparathyroidism and recurrent laryngeal nerve injury are more frequent following reoperation for PNH. The factors significantly associated with PNH were: older age, concurrent lymph node dissection, and chronic lymphocytic thyroiditis. Gender, previous neck irradiation, presentation at diagnosis (symptomatic or incidental), substernal goiter, thyroidectomy for hyperthyroidism, prior thyroid surgery, malignant histology, the extent of the surgery (total versus non-total thyroidectomy), the use of energy-based vessel sealing devices, the use of the hemostatic agent Surgicel, and the placement of a surgical drain were not significantly associated with PNH. Conclusion Hematoma after thyroid surgery is an uncommon complication, but it is related to significant postoperative morbidity. A better understanding of the risk factors and of the time until hematoma formation can help target high-risk patients for preventive measures and closer postoperative observation.

Abstract Introduction The COVID-19 pandemic has had a high impact on surgical training around the world due to required measures regarding the suspension of elective procedures and the dismissal of nonessential personnel. Objectives To understand the impact the pandemic had on head and neck surgery training in Brazil. Methods We conducted a 29-question online survey with head and neck surgery residents in Brazil, assessing the impact the pandemic had on their training. Results Forty-six residents responded to the survey, and 91.3% of them reported that their residency was affected by the pandemic, but most residents were not assigned to work directly with patients infected with the new coronavirus (71.4%). All residents reported decrease in clinic visits and in surgical procedures, mostly an important reduction of ∼ 75%. A total of 56.5% of the residents described that the pandemic has had a negative impact on their mental, health and only 4 (8.7%) do not have any symptoms of burnout. The majority (78.3%) of the residents reported that educational activities were successfully adapted to online platforms, and 37% were personally infected with the virus. Conclusion Most surgical residencies were greatly affected by the pandemic, and residents had an important decrease in surgical training. Educational activities were successfully adapted to online modalities, but the residency programs should search for ways of trying to compensate for the loss of practical activities.

ABSTRACT Background: The aim of this study was to address the first cases of TOETVA done in Brazil, by TOETVA-Bra study group, regarding safety and complications. Materials and Methods: Series of the first 93 TOETVAs cases in Brazil. All authors except LPK, AJG JOR and RPT received TOETVA training including cadaveric hands-on in Thailand or United States (Johns Hopkins Medicine) during 2017. After they came back to Brazil and started doing their first TOETVA cases in the cities of Rio de Janeiro, Sao Paulo and Chapecó they agreed to collaborate and gather data using an online spreadsheet. All patients were submitted to the technique described by Anuwong. Results: A total of 93 patients underwent TOETVA. Most patients (58.1%) were submitted to total thyroidectomy and 59.1% had benign disease. Two patients (2.2%) needed conversion to open surgery. Five patients (9.3%) developed transient hypoparathyroidism and there were 3 (2.0%) temporary recurrent laryngeal nerve palsy. There was one (0.7%) permanent unilateral palsy. Twenty patients had some sort of complication, 16.1% were minor and 5.4% were major. A total of 73 patients (78.5%) had an uneventful recovery. Conclusion: The technique is reproducible with a low complication rate. While further studies are needed to confirm equivalency, early efforts suggest that TOETVA is not inferior to traditional open thyroidectomy in appropriately selected patients.

Resumo Introdução: A cirurgia mais comum da região cervical é a tireoidectomia. Atualmente, várias tecnologias estão disponíveis para hemostasia intraoperatória. Objetivo: Comparar o desempenho de três tecnologias (elétrica monopolar e bipolar e ultrassônica) no tempo operatório e complicações pós-operatórias. Método: Pacientes submetidos à tireoidectomia total sem tratamento prévio foram incluídos. Desenho científico usado: estudo de série prospectiva. Resultados: Foram incluídos 834 pacientes, 661 mulheres (79,3%) e 173 homens (20,7%). O diagnóstico foi de neoplasia maligna em 528 pacientes (63,3%) e de doença benigna em 306 pacientes (36,7%). O bisturi elétrico monopolar foi usado em 280 pacientes (33,6%), energia bipolar em 210 (25,2%) e ultrassônica em 344 (41,3%). O tempo operatório foi significantemente menor com bisturi ultrassônico ou bipolar quando comparado com elétrico. Em um modelo de regressão linear, sexo, diagnóstico de malignidade e tipo de energia foram significantes para duração do procedimento. Os pacientes operados com bisturi ultrassônico ou bipolar apresentaram incidência significantemente menor de hipoparatireoidismo. Conclusão: O uso do bisturi ultrassônico ou bipolar reduz de forma significante o tempo operatório e a incidência de hipoparatireoidismo transitório.

Resumo Introdução: A biópsia de linfonodo sentinela é o padrão-ouro para estadiamento de melanomas cutâneos em cabeça e pescoço. Objetivo: Avaliar aspectos técnicos, positividade e efeito prognóstico da pesquisa de linfonodo sentinela cervico-facial. Método: Estudo retrospectivo, unicêntrico. Entre 2009 e 2014, 49 pacientes com melanoma cutâneo de cabeça e pescoço foram operados no Instituto do Câncer do Estado de São Paulo (ICESP). Resultado: Dos 49 pacientes, cinco tiveram metástases cervicais detectáveis à admissão. Níveis de Clark e Breslow e índice mitótico foram preditores de risco de óbito. Entre os 31 pacientes submetidos à biópsia de linfonodo sentinela, três tiveram resultados positivos (9,7%). Faleceram dois (66,6%) dos portadores de micrometástases e cinco (17,8%) entre os pacientes com linfonodos sentinela negativos. A média do índice de Breslow foi de 11,3 mm entre os casos positivos e 4,3 mm nos negativos. A positividade foi associada aos níveis de Clark e Breslow. A localização malar teve efeito protetor. A média de tempo de sobrevivência dos pacientes com índice mitótico abaixo de 3,5 foi de 181 meses e para aqueles com índice mitótico acima de 3,5 foi de 63,4 meses. Conclusão: A frequência de linfonodo sentinela positivo foi mais baixa do que a encontrada em outros estudos, apesar de a amostra ter sido composta por melanomas avançados. O índice mitótico foi importante na predição de prognóstico.

Abstract Introduction: Sentinel lymph node biopsy is the gold standard procedure for head and neck cutaneous melanoma staging. Objective: To evaluate the technical aspects, positivity and prognostic effect of the cervico-facial sentinel lymph node biopsy. Methods: Retrospective, unicentric study. From 2009 to 2014, 49 patients with cutaneous melanoma of the head and neck underwent surgery at Instituto do Câncer do Estado de São Paulo (ICESP). Results: Of the 49 patients, 5 had cervical metastasis at the moment of admission. Clark, Breslow and mitotic index were predictors of death. Among the 31 patients undergoing sentinel lymph node biopsy, 3 had positive sentinel lymph nodes (9.7%). Deaths were recorded in two of the cases with positive sentinel lymph nodes (66.6%), and in 5 (17.8%) of the patients with negative lymph nodes. The mean Breslow index was 11.3 mm for primary melanomas with positive sentinel lymph nodes and 4.3 mm for those with negative sentinel lymph nodes. Positivity was associated with Clark and Breslow levels. Malar location showed a protective effect on prognosis. The mean survival for patients with a mitotic index <3.5 was 181 months and 63.4 months for those with a mitotic index >3.5. Conclusion: The frequency of positive sentinel lymph node biopsy in patients with malignant melanoma of the head and neck was lower than in other studies, although the sample consisted of individuals with advanced melanomas. The mitotic index was important for prognosis prediction.

OBJECTIVES: Craniofacial resection (CFR) procedures for craniofacial tumors with cranial extension are often extensive. Although CFRs may yield good oncological results, there are concerns about high perioperative morbidity and mortality. This study aimed to determine risk factors for perioperative mortality after open CFR in terms of deaths occurring during index hospitalizations. METHODS: We conducted a retrospective analysis of CFRs conducted at a tertiary oncology hospital from May 2009 through December 2018. RESULTS: Our analysis included data from the medical records of 102 patients, the majority of whom were male (n=74, 72.5%). The mean age was 61 years (±18.3 years). Skin malignancies (n=64, 63.4%) accounted for nearly two-thirds of the treated tumors, and most of these were squamous cell carcinoma. Postoperative medical complications occurred in 33 patients (33%), and surgical complications occurred in 48 (47%). Multivariate analysis revealed the only independent risk factors for perioperative deaths to be the presence of intracranial tumor extension on preoperative imaging (hazard ratio [HR]=4.56; 95% confidence interval [CI]: 1.74-11.97; p=0.002) and the unexpected emergence of postoperative neurological dysfunction (HR=10.9; 95% CI: 2.21-54.3; p=0.003). CONCLUSIONS: In our study, factors related to tumor extension were associated with a higher risk of perioperative death.