Resumo Introdução A osteonecrose dos maxilares relacionada à medicação é uma complicação grave da terapia antirreabsortiva e antiangiogênica, com opção de tratamento limitada e grande impacto na qualidade de vida do paciente. Objetivo Avaliar os fatores de risco associados à osteonecrose dos maxilares relacionada à medicação em pacientes oncológicos em tratamento com bifosfonato Além disso, os níveis salivares de interleucina-6 (IL-6) foram medidos para investigar sua associação com a gravidade e o risco de osteonecrose dos maxilares relacionada à medicação. Método Estudo caso-controle com 74 pacientes com metástases ósseas de tumores sólidos e mieloma múltiplo. Os pacientes foram divididos em três grupos: 1) em tratamento por bifosfonato com osteonecrose dos maxilares relacionada à medicação; 2) submetidos ao bifosfonato sem osteonecrose dos maxilares relacionada à medicação; e 3) pré-tratamento de bifosfonato. Os dados demográficos e médicos dos pacientes foram coletados para avaliar o risco. A avaliação clínica foi feita para diagnosticar osteonecrose dos maxilares relacionada à medicação e a saliva não estimulada foi coletada para quantificação da IL-6. Resultados Observou-se que os pacientes diagnosticados com osteonecrose dos maxilares relacionada à medicação foram submetidos a maior número de doses de bifosfonato (p = 0,001) e protocolo de infusão mensal (p = 0,044; OR = 7,75). Pacientes que não tiveram acompanhamento de rotina com dentistas especializados durante a terapia com bifosfonato e tabagismo foram associados ao osteonecrose dos maxilares relacionada à medicação (p = 0,019; OR = 8,25 e p = 0,031; OR = 9,37, respectivamente). O grupo 1 apresentou maior frequência de tratamento com quimioterapia e corticosteroides concomitantes ao bifosfonato e procedimentos odontológicos cirúrgicos (p = 0,129). Os níveis salivares de IL-6 não apresentaram diferença estatisticamente significante entre os grupos (p = 0,571) ou associação com a gravidade do osteonecrose dos maxilares relacionada à medicação (p = 0,923). Conclusão Maior número de ciclos de bifosfonato, protocolo de infusão mensal, ausência de acompanhamento odontológico para manutenção da saúde bucal e tabagismo foram associados ao osteonecrose dos maxilares relacionada à medicação. O acompanhamento odontológico especializado durante o tratamento demonstrou ser importante na prevenção dessa complicação.

Abstract Introduction Medication-related osteonecrosis of the jaws is a severe complication of the use of antiresorptive and antiangiogenic therapy, with limited treatment options and great impact on patient’s quality pf life. Objective The aim of this study was to assess the risk factors associated with medication-related osteonecrosis of the jaws in oncologic patients undergoing bisphosphonate treatment. In addition, salivary levels of interleukin-6, IL-6, were measured to investigate their association with severity and risk of medication-related osteonecrosis of the jaws. Methods Case-control study with 74 patients with bone metastases from solid tumors and multiple myeloma was included. Patients were divided into three groups: 1) those undergoing bisphosphonate treatment with medication-related osteonecrosis of the jaws; 2) those undergoing bisphosphonate without medication-related osteonecrosis of the jaws; and 3) those with bisphosphonate pretreatment. The demographic and medical data of the patients were collected to assess risk. The clinical evaluation was performed to diagnose medication-related osteonecrosis of the jaws and unstimulated saliva was collected for quantification of IL-6. Results As result, it was observed that patients diagnosed with medication-related osteonecrosis of the jaws were submitted to higher number of bisphosphonate doses (p= 0.001) and monthly infusion protocol (p= 0.044; OR = 7.75). Patients who did not have routine followup with specialized dentists during therapy with bisphosphonate and smoking were associated with medication-related osteonecrosis of the jaws (p= 0.019; OR = 8.25 and p= 0.031; OR = 9.37 respectively). Group 1 had a higher frequency of treatment with chemotherapy and corticosteroids concomitant with bisphosphonate, and surgical dental procedures (p= 0.129). Salivary IL-6 levels showed no statistically significant difference between the groups (p= 0.571) or association with medication-related osteonecrosis of the jaws severity (p= 0.923). Conclusion A higher number of bisphosphonate cycles, monthly infusion protocol, no dental follow-up for oral health maintenance and smoking were associated with medication-related osteonecrosis of the jaws. Specialized dental follow up during bisphosphonate treatment has been shown to be an important factor in preventing this complication.

RESUMO Objetivo: O ceratocisto odontogênico têm uma alta taxa de recorrência e comportamento clínico agressivo. O evento chamado transição epitelial-mesênquima (TEM) é um processo no qual a célula epitelial perde suas características epiteliais e adquire propriedades típicas das células mesenquimais. Estudos já demonstraram que o ceratocisto odontogênico tem expressão de marcadores tumorais, mas a falta de esclarecimento sobre seu mecanismo de desenvolvimento e composição molecular faz com que as opções terapêuticas permaneçam limitadas. O objetivo deste estudo é avaliar a expressão das proteínas marcadoras de transição epitelial-mesênquima nestas lesões, correlacionando a expressão destas proteínas com os aspectos clínicos de cada caso. Métodos: Os pacientes com diagnóstico de ceratocisto odontogênico, tratados pelo Serviço de Cirurgia Bucomaxilofacial do Hospital Erasto Gaertner, Curitiba, Brasil, no período entre 2016 e 2019, foram avaliados por análise imunohistoquímica, para avaliar a expressão dos marcadores transição epitelial-mesênquima (Vimentina, beta-catenina e E-cadherina). Resultados: Foram incluídos 18 pacientes, com idade média de 43 anos, e a maioria deles eram do sexo masculino. A mandíbula foi mais afetada do que a maxila. Não foi observada associação entre as características clínicas dos cistos e o perfil imuno-histoquímico das proteínas transição epitelial-mesênquima. Conclusão: A positividade da E-caderina e a negatividade da vimentina demonstram que a sua função está preservada. A perda da função da E-caderina está associada a um pior prognóstico. Identificar o processo da transição epitelial-mesênquima como um marcador de prognóstico para cistos e tumores odontogênicos pode ser uma ferramenta importante para definir o tratamento dessas lesões.

ABSTRACT Objective: Odontogenic keratocysts have a high recurrence rate and aggressive clinical behavior. The event called epithelial-mesenchymal transition is a process in which the epithelial cell loses its epithelial characteristics and acquires properties typical of mesenchymal cells. Studies have already demonstrated that odontogenic keratocysts has expression of tumor markers, but the lack of clarification about its development mechanism and molecular composition makes the therapeutic options remain limited. The aim of this study is to evaluate the expression of epithelial-mesenchymal transition marker proteins in these lesions, correlating the expression of these proteins with clinical aspects of each case. Methods: Patients with odontogenic keratocysts diagnoses, treated by the Department of Oral and Maxillofacial Surgery of the Erasto Gaertner Hospital, Curitiba, Brazil in the period between 2016 and 2019 were evaluated by immunohistochemical analysis, to assess the expression of epithelial-mesenchymal transition markers (Vimentin, beta-catenin and E-cadherin) by qualitative analysis. Results: Eighteen patients were included, with a mean age of 43 years, and most of them were male. The mandible was more affected than the maxilla. No association between the clinical characteristics of the cysts and the immunohistochemical profile for epithelial-mesenchymal transition proteins was observed. Conclusion: The positivity of E-cadherin and negativity of vimentin demonstrates that its function is preserved. Loss of function of E-cadherin is associated with worse prognosis. The identification of the epithelial-mesenchymal transition process as a prognostic marker for odontogenic cysts and tumors could be an important tool for defining treatment.

Abstract It is largely known that some oral diseases can be diagnosed based upon their clinical manifestation combined with the patient's medical history and generally not depending on examination. This is the case of some bone diseases such as osteoradionecrosis of the jaw (ORNJ), osteomyelitis of the jaw (OMJ), and medication-related osteonecrosis of the jaw (MRONJ). The present study aimed to analyze the histopathological features of these specific bone diseases in order to evaluate similarities and differences. Forty-four bone specimens resected from each bone disease (22 cases of ORNJ, 6 cases of OMJ, and 16 cases of MRONJ) were analyzed by two experienced oral pathologists without prior knowledge of the diagnosis, considering bone tissue condition, inflammation, vascularization, and the presence of microorganisms. In addition, the examiners formulated a diagnostic hypothesis for each specimen. Many histopathological similarities were found among the diseases, especially considering the presence of necrotic bone, inflammation, and microorganisms. Statistically significant differences were detected in empty bone lacunae, which was decreased in ORN (p = 0.042), and considering neutrophil count, which was low in the MRONJ group (p ≤ 0.001). The Kappa coefficient was calculated and agreement was detected based on the histopathological parameters, but not for diagnostic suggestion (p=0.23). In conclusion, histopathological aspects of ORNJ, OMJ, and MRONJ do not permit a conclusive diagnosis, emphasizing the necessity of a detailed clinical report.

Stem cell-based regenerative medicine is one of the most intensively researched medical issues. Pre-clinical studies in a large-animal model, especially in swine or miniature pigs, are highly relevant to human applications. Mesenchymal stem cells (MSCs) have been isolated and expanded from different sources. Objective: This study aimed at isolating and characterizing, for the first time, bone marrow-derived MSCs (BM-MSCs) from a Brazilian minipig (BR1). Also, this aimed to validate a new large-animal model for stem cell-based tissue engineering. Material and Methods: Bone marrow (BM) was aspirated from the posterior iliac crest of twelve adult male BR1 under general anesthesia. MSCs were selected by plastic-adherence as originally described by Friedenstein. Cell morphology, surface marker expression, and cellular differentiation were examined. The immunophenotypic profile was determined by flow cytometry. The differentiation potential was assessed by cytological staining and by RT-PCR. Results: MSCs were present in all minipig BM samples. These cells showed fibroblastic morphology and were positive for the surface markers CD90 (88.6%), CD29 (89.8%), CD44 (86.9%) and negative for CD34 (1.61%), CD45 (1.83%), CD14 (1.77%) and MHC-II (2.69%). MSCs were differentiated into adipocytes, osteoblasts, and chondroblasts as demonstrated by the presence of lipidic-rich vacuoles, the mineralized extracellular matrix, and the great presence of glycosaminoglycans, respectively. The higher gene expression of adipocyte fatty-acid binding protein (AP2), alkaline phosphatase (ALP) and collagen type 2 (COLII) also confirmed the trilineage differentiation (p<0.001, p<0.001, p=0.031; respectively). Conclusions: The isolation, cultivation, and differentiation of BM-MSCs from BR1 makes this animal eligible as a useful large-animal model for stem cell-based studies in Brazil.

INTRODUCTION: Radiotherapy (RT) of head and neck neoplasms often damages the salivary glands. AIM: To examine the pattern of morphologic changes resulting from RT of the head and neck region in minipig parotid glands in a clinical and experimental research setting. METHODS: Twelve 18-month-old male Brazilian minipigs weighing 30-40 kg were selected. Eight minipigs were assigned to the experimental group (group 1) and 4 to the control group (group 2). The RT was performed under general anesthesia at Erasto Gaertner Hospital, Curitiba, Brazil, using an á/â ratio of 2.5. The minipigs from group 1 underwent 3 sessions of irradiation with Cobalt 60 of the head and neck, bilaterally, with 3 exposures of 8 Gy each at 7-day intervals for a total dose of 24 Gy. The animals were sacrificed 12 weeks post-RT. RESULTS: The irradiated parotid glands displayed reductions in the size and number of acini as well as loss of secretory granules. The presence of fibrosis and loss of parenchyma relative to non-irradiated glands were observed, with an average reduction in volume of 54%. CONCLUSIONS: Our results demonstrate that this model for parotid gland damage resulting from an RT regimen appears to be useful for preclinical large animal studies of RT-induced damage and testing novel potential treatment options. Although recent advances in radiation therapy, such as intensity-modulated radiation therapy, have reduced the dose and limited the field of radiation, considerable salivary gland injury still occurs and can greatly impact the patient's quality of life after cancer treatment.

OBJETIVO: A maioria das neoplasias malignas de cabeça e pescoço é diagnosticada em estágios avançados. O alto risco de desenvolver um segundo tumor primário (STP) diminui a taxa de sobrevida dos pacientes. STP piora significativamente o prognóstico e estudos sobre ele devem ser realizados para se descobrir seus fatores de risco e melhor forma de tratamento. O principal objetivo deste estudo foi analisar a ocorrência de STP em pacientes com carcinoma epidermóide bucal (CEB) tratados no Hospital Erasto Gaertner (HEG), Curitiba, PRP, Brasil, num período de 16 anos. METODOLOGIA: Um estudo retrospectivo foi realizado a fim de revisar os pacientes com CEB que desenvolveram STP entre Janeiro de 1990 e Dezembro de 2005. Os dados demográficos e clínicos foram coletados através dos prontuários médicos dos pacientes e foram analisados por estatística descritiva. RESULTADOS: Neste período, 34.637 pacientes foram admitidos no HEG. Um total de 1637 (4,4%) pacientes recebeu diagnóstico de CEB, dos quais 37 (2,7%) desenvolveram STP. Os pacientes que desenvolveram STP eram 29 (78,4%) homens e 8 (21,6%) mulheres, com média de idade de 58 anos. Os sítios anatômicos mais frequentes para o STP foram a boca, orofaringe e esôfago; a taxa de sobrevivência foi de 27%. CONCLUSÃO: Pacientes tratados de CEB devem ser examinados cuidadosamente e monitorados regularmente por causa do alto risco de desenvolver um STP, especialmente aqueles que mantêm os hábitos de tabagismo e etilismo.

PURPOSE: Most head and neck malignant neoplasias are diagnosed in advanced stages. Another threatening element to the patients' survival chances and quality of life is the high risk of developing a second primary tumor (SPT). SPT significantly worsens prognosis, and for that reason patients must be monitored for early diagnosis. The main objective of this study was to analyze the occurrence of SPTs in patients with oral squamous cell carcinoma (OSCC) treated in Erasto Gaertner Hospital (EGH), Curitiba, PR, Brazil, in a period of 16 years. METHODS: Design: retrospective study. The sample comprised patients with OSCC who developed SPT between January 1990 and December 2005. Demographic and clinical data were recorded form the patients' medical charts and analyzed with descriptive statistics. RESULTS: During this period, 34,637 patients were admitted at EGH. A total of 1,637 (4.4%) patients were diagnosed with OSCC, and 37 (2.7%) developed a SPT. Patients who developed SPT were 29 (78.4%) male and 8 (21.6%) female, with a median age of 58 years old. The most frequent anatomical SPT site was the mouth, oropharynx and oesophagus, with an overall survival of 27%. CONCLUSION: Patients treated from OSCC must be carefully monitored because of the increased risk of SPT, especially when there is a continuous history of tobacco and alcohol consumption.