Abstract The objective of this study was to evaluate the fractal dimension (FD) and lacunarity of the mandibular bone, comparing patients with and without osteoradionecrosis (ORN). In a cross-sectional study with a control group, 25 patients were included and divided into a case group (with ORN, n = 14) and a control group (without ORN, n = 11). A digital panoramic radiograph taken after the end of radiotherapy (RT) was evaluated for each patient. FD and lacunarity of the mandibular bone were determined using ImageJ software. Descriptive, bivariate, and ROC curve analyses were performed. Cohen's d effect sizes were calculated. Significance was established at p < 0.05. The mean FD and lacunarity values were not significantly different between the groups. The area under the curve for FD and lacunarity were 0.579 and 0.661, respectively. The cut-off point for FD was ≤1.1714 and for lacunarity, > 0.3821, correctly classifying the majority of cases and controls. Most participants in the case group (63.6%) had a FD ≤ 1.1714 and the majority of participants in the control group (63.6%) had a FD >1.1714 (p = 0.395). For lacunarity, most individuals in the case group (72.7%) had a value > 0.3821 and most participants in the control group (63.6%) had a value ≤ 0.3821 (p = 0.198). In conclusion, the FD and lacunarity values did not show statistically significant differences between patients with and without ORN. However, the moderate and large magnitude of the effects seem to indicate that the results may be clinically relevant. (FD ORN . (ORN) crosssectional cross sectional 2 14 11. 11 11) RT (RT patient software Descriptive bivariate performed Cohens Cohen s calculated 005 0 05 0.05 groups 0579 579 0.57 0661 661 0.661 respectively cutoff cut off 11714 1 1714 ≤1.171 03821 3821 controls 63.6% 636 63 6 (63.6% 1.171 >1.171 0.395. 0395 0.395 395 0.395) 72.7% 727 72 7 (72.7% 0.382 0.198. 0198 0.198 198 0.198) conclusion However relevant (ORN 00 0.0 057 57 0.5 066 66 0.66 1171 171 ≤1.17 0382 382 63.6 (63.6 1.17 >1.17 039 0.39 39 72.7 (72.7 0.38 019 0.19 19 0. 5 06 0.6 117 17 ≤1.1 038 38 63. (63. 1.1 >1.1 03 0.3 3 72. (72. 01 0.1 ≤1. (63 1. >1. (72 ≤1 (6 >1 (7 (

Abstract The aim of this study was to evaluate the time elapsed from first symptoms to the treatment of oral and oropharyngeal cancer (OOC) and to identify variables associated with treatment delay. This is an observational study with retrospective and prospective data collection. Patients with a diagnosis of OOC seen at the Head and Neck Surgery outpatient clinic of a Brazilian public hospital were included and followed up to treatment initiation. Participants answered a questionnaire for the collection of socioeconomic, demographic, cultural, and clinical information, as well as information about the time elapsed from first symptoms to the first appointment with a head and neck surgeon. Time to treatment was classified into four intervals: 1- first symptoms to first medical appointment; 2- first medical appointment to specialized medical care; 3- specialized medical care to preparation for treatment; and 4- preparation for treatment to treatment initiation. Bivariate statistics were computed. Out of 100 participants, nine died before treatment. Mean time to treatment was 217 days. Highest mean time was observed for interval 2 (94 days), followed by interval 1 (63 days), interval 4 (39 days), and interval 3 (21 days). At interval 1, a longer time was associated with severe alcohol consumption, severe smoking, and family history of cancer. At interval 2, the delay was associated with appointment with a general practitioner, clinical diagnosis of disease other than cancer, and antibiotic prescription. At interval 4, delay in treatment was associated with surgical treatment. Patients with OOC experience delays from symptom onset to treatment initiation. The longest interval was associated with professional delay, followed by patient delay in help-seeking. (OOC initiation socioeconomic demographic cultural surgeon intervals computed 10 participants 21 days 94 (9 days, , days) 63 (6 39 (3 (2 . consumption smoking practitioner prescription helpseeking. helpseeking help seeking. seeking help-seeking 9 ( 6

Resumen Las lesiones orales de tejido blando son infrecuentes en los recién nacidos, pueden conducir a una alimentación, crecimiento, y desarrollo cognitivo inapropiados. El fibroma osificante periférico es una lesión reactiva de la encía, con solo cinco casos reportados en recién nacidos. Objetivo: Reportar un caso de fibroma osificante periférico en un recién nacido, y discutir las complicaciones asociadas a dientes natales/neonatales. Caso clínico: Masculino de 4 meses de edad, mexicano, presentó dos dientes natales que fueron extraídos a los quince días de nacimiento. Posteriormente, se observó un crecimiento de tejido blando en esta área, con dos zonas radiopacas identificadas radiográficamente. Con el diagnóstico presuntivo de lesión reactiva, se procedió a la biopsia excisional, con evolución satisfactoria durante el seguimiento. Conclusiones: El fibroma osificante periférico debe considerarse como una potencial complicación por la presencia o extracción de dientes natales/neonatales, y debe tratarse oportunamente debido a sus repercusiones clínicas.

Abstract Oral soft tissue injuries are rare in newborns and can lead to inappropriate feeding, growth, and cognitive development. Peripheral ossifying fibroma is a reactive lesion of the gingiva, with only five cases reported in newborns. Objective: To report a case of peripheral ossifying fibroma in a newborn, and to discuss the complications associated with natal/neonatal teeth. Clinical case: A 4-month-old Mexican male presented two natal teeth that were extracted fifteen days after birth. Subsequently, soft tissue growth was observed in this area, with two radiopaque zones radiographically identified. With the presumptive diagnosis of reactive lesion, an excisional biopsy was performed, with satisfactory evolution during follow-up. Conclusions: Peripheral ossifying fibroma should be considered as a potential complication due to the presence or extraction of natal/neonatal teeth, and should be treated promptly due to its clinical repercussions.

Resumo Lesões de tecidos moles orais são raras em recém-nascidos e podem levar a alimentação inadequada, crescimento e desenvolvimento cognitivo. O fibroma ossificante periférico é uma lesão reativa da gengiva, com apenas cinco casos relatados em recém-nascidos. Objetivo: Relatar um caso de fibroma ossificante periférico em recém-nascido e discutir as complicações associadas aos dentes natais/neonatais. Caso clínico: Um menino mexicano de 4 meses de idade apresentou dois dentes natais que foram extraídos quinze dias após o nascimento. Posteriormente, observou-se crescimento de tecidos moles nesta área, com duas zonas radiopacas identificadas radiograficamente. Com o diagnóstico presuntivo de lesão reativa, foi realizada biópsia excisional, com evolução satisfatória durante o seguimento. Conclusões: O fibroma ossificante periférico deve ser considerado como uma complicação potencial devido à presença ou extração de dentes natais/neonatais, devendo ser tratado prontamente devido às suas repercussões clínicas.

Abstract: Tobacco smoking involves a high risk of human malignancies, including oral cancer, because it contains multiple carcinogens that cause genetic instability. Thus, a worse prognosis would be expected for cancer patients who are smokers. The aim of this study was to assess the DNA damage response through the expression of checkpoint kinase 2 (CHK2), H2A histone family member X (H2AX), and P53 among smokers and non-smokers with oral squamous cell carcinoma (OSCC). Associations between immunoexpression of proteins and clinicopathological data and histopathological grading were also analyzed. A total of 35 individuals (18 non-smokers and 17 smokers) with OSCC of the tongue and/or floor of the mouth were included. Immunohistochemistry for H2AX was conducted for the identification of double-strand breaks, CHK2, and P53 to evaluate the expression of this protein in cell cycle regulation. The sample consisted of 22 males and 13 females, with a mean age of 63.9±11.8 years. OSCC of non-smokers were well-differentiated tumors in 50% of the cases, and those of smokers were equally distributed into moderately differentiated and poorly differentiated tumors (35.3% each). Overall, 31 (88.6%) cases were CHK2-positive, 27 (77.1%) were H2AX-positive, and 23 (65.7%) were P53-positive, with no difference between smokers and non-smokers (p > 0.05). No association was found between proteins and clinicopathologic data (p > 0.05). Similarities in CHK2, H2AX, and P53 immunohistochemical staining patterns were observed between smokers and non-smokers, and immunoexpression was not associated with clinicopathological parameters. However, the findings indicated consistent expression of these proteins in OSCC.

Abstract Head and neck radiotherapy causes quantitative and qualitative changes in saliva. The objective of this case-control study was to evaluate the salivary biomarkers associated with bone remodeling and tissue repair in patients submitted to radiotherapy for head and neck cancer treatment, compared with non-irradiated individuals. Total unstimulated saliva was collected for ELISA assay analysis of receptor activator for nuclear factor κ B (RANK) and its ligand (RANK-L), osteoprotegerin, matrix metalloproteinase-9/ tissue inhibitor of metalloproteinase-2, vascular endothelial growth factor, and epidermal growth factor. Statistics were performed, and revealed that salivary RANK (p = 0.0304), RANK-L (p = 0.0005), matrix metalloproteinase-9/ tissue inhibitor of metalloproteinase-2 (p = 0.0067), vascular endothelial growth factor (p = 0.0060), and epidermal growth factor (p < 0.0001) were reduced in patients, compared with the control group. Osteoprotegerin did not differ between the groups (p = 0.3765). Salivary biomarkers did not differ according to radiotherapy completion time (p > 0.05). In conclusion, the lower output of the salivary molecules – essential for bone remodeling and tissue repair – may disrupt tissue homeostasis and play a role in the pathogenesis of the radiotherapy-induced deleterious effects in the oral cavity.

Resumo Introdução: Um ressurgimento da sífilis no Brasil tem sido relatado nos últimos anos. Objetivo: Investigar a frequência, as características demográficas e clínicas dos pacientes com sífilis adquirida com envolvimento oral que receberam atendimento médico em um centro de referência em medicina oral em um hospital público brasileiro. Método: Estudo retrospectivo, abrangeu 12 anos, feito para identificar tendências de mudança na sífilis. Registros médicos de todos os pacientes diagnosticados com sífilis adquirida que receberam atendimento médico na clínica de medicina oral do hospital de 2005 a 2016 foram revisados e os dados demográficos e clínicos foram coletados. Resultados: Foram diagnosticas 85 pacientes com sífilis adquirida, com um aumento significativo no número de casos nos últimos 5 anos. A idade dos pacientes variou de 16 a 76 anos, com pico na terceira e quarta décadas; 48 casos eram do sexo masculino (56,5%) e 37 do sexo feminino (43,5%). A maioria das lesões orais apareceu como úlceras ou placas únicas, os lábios e a língua representaram os locais mais afetados. Todos os casos foram positivos para Venereal Disease Research Laboratory e Fluorescent Treponemal Antibody Absorption Test e o tratamento foi feito com penicilina G benzatina na maioria dos casos (84,7%). Conclusão: A frequência da sífilis oral tem aumentado com o tempo e as lesões orais podem representar uma pista diagnóstica; portanto, os profissionais de saúde bucal devem ser conscientizados e devidamente treinados na tentativa de desenvolver um alto grau de suspeição clínica no diagnóstico da sífilis.

Abstract Introduction: A resurgence of syphilis in Brazil has been reported in recent years. Objective: With this in mind, the present study sought to investigate the frequency, demographics, and clinical characteristics of patients with acquired syphilis with oral involvement who received medical care at an Oral Medicine Reference Center in a Brazilian Public Hospital. Methods: A retrospective study, spanning a period of 12 years, was performed to identify changing trends in syphilis over time. Medical records from all patients diagnosed with acquired syphilis who received medical care at the Hospital's Oral Medicine Clinic from 2005 to 2016 were reviewed, and the demographic and clinical data were collected. Results: A total of 85 patients had been diagnosed with acquired syphilis, with a significant increase in the number of cases over the past 5 years. Patients ranged from 16 to 76 years of age, with a peak in the third and fourth decades. Forty-eight cases affected males (56.5%), while 37 cases affected females (43.5%). Most of the oral lesions appeared as unique ulcers or plaques, with the lips and tongue representing the most affected sites. All cases were positive for Venereal Disease Research Laboratory or Fluorescent Treponemal Antibody Absorption, and treatment was performed with Penicillin G benzathine in most cases (84.7%). Conclusion: The frequency of oral syphilis has been rising over time and oral lesions may well represent a diagnostic clue; therefore, oral health professionals must be made aware and properly trained in an attempt to develop a high degree of clinical suspicion in the diagnosis of syphilis.

Abstract About 92,000 new cases of oropharynx carcinoma are expected to occur annually worldwide. There is no consensus about the best therapy for these advanced tumors. The objective of the present study was to evaluate overall and disease-free survival rates of patients with advanced oropharynx squamous cell carcinoma, comparing surgery + radiotherapy with chemotherapy + radiotherapy. Medical records of patients were reviewed. Previously treated tumors were excluded. Clinical, demographic and microscopic information was collected, and p16 staining was performed. Kaplan-Meier survival curves were plotted. Forty-seven cases were included, 41 men and 6 women, having a mean age of 56.3 years. Most patients were smokers (85.1%) and consumed alcohol (74.5%). Patients were stage III (21.3%) or IV (78.7%). Most lesions affected the base of the tongue (36.2%). Of the 23 cases available for p16 testing, 3 were positive (13.0%). There was no difference between the overall and the disease-free survival rates for the two treatment modalities (p>0.05), even when only resectable tumors were compared. Seventeen cases experienced recurrence (36.2%); 16 (34.0%) patients remained alive without disease; 15 (31.9%) died due to disease; 9 (19.2%) were recurrent at the last follow-up. The two treatment protocols were equally efficient in treating advanced oropharynx squamous cell carcinoma, since both promoted similar overall and disease-free survival rates. The results and interpretations related herein mostly regard “conventional” oropharyngeal squamous cell carcinomas, as opposed to HPV-associated tumors.

Abstract Cytokines and chemokines have a fundamental role in the maintenance of inflammation and bone response, which culminate in the development of chronic periapical lesions. Regulatory (Treg) and Th17 cytokines play a key role in regulating the immune response involved in this process. The aim of this study was to investigate the role of Treg and Th17 cells in chronic inflammatory periapical disease, by comparing the expression of the immunoregulatory mediators TGF-β, IL-10, CCL4, and the proinflammatory IL-17 and CCL20 in the periapical tissue of teeth with pulp necrosis, with and without associated chronic lesions. Eighty-six periapical tissue samples were obtained from human teeth. The samples were divided into three groups: pulp necrosis with a periapical lesion (n=26); pulp necrosis without a periapical lesion (n=30), and control (n=30). All samples were submitted to histopathological analysis and cytokine and chemokine measurement through ELISA. Statistical analyses were done with Kruskal-Wallis and Mann-Whitney tests and Spearman correlation. The group with pulp necrosis and a periapical lesion showed a higher expression of CCL4 and TGF-β in comparison with pulp necrosis without a lesion. CCL20 was higher in the group with a periapical lesion when compared to the control. In all groups there was a weak positive correlation between IL-17/CCL20, IL-10/CCL4, and IL-17/TGF-β. Both types of cytokines, pro-inflammatory and immunoregulatory, occur simultaneously in periapical tissue. However, a rise in immunosuppressive cytokines and chemokines (CCL4 and TGF-β) in periapical lesions suggests a role of these cytokines in stable periapical disease.