PAULO HENRIQUE BRAZ DA SILVA
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ODE, FO - Docente
LIM/52 - Laboratório de Virologia, Hospital das Clínicas, Faculdade de Medicina
LIM/52 - Laboratório de Virologia, Hospital das Clínicas, Faculdade de Medicina
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- Morphology, Volume, and Density Characteristics of the Parotid Glands before and after Chemoradiation Therapy in Patients with Head and Neck Tumors(2020) SANTOS, Wellington Pereira dos; GOMES, Joao Pedro Perez; NUSSI, Amanda Drumstas; ALTEMANI, Joao Mauricio; SANTOS, Maria Teresa Botti Rodrigues dos; HASSEUS, Bengt; GIGLIO, Daniel; BRAZ-SILVA, Paulo Henrique; COSTA, Andre Luiz FerreiraThe multimodal approach for patients with head and neck cancer (HNC) includes treatment with chemoradiation therapy (CRT). A common concern regarding CRT side effects is the occurrence of structural and physiological alterations of the salivary glands due to exposure to ionizing radiation. The aim of this study is to examine the morphology, volume, and density of the parotid glands before and after CRT in HNC patients. A total of 49 HNC patients treated exclusively with CRT were included in the study. Ninety-eight parotid glands were evaluated before and after treatment by using contrast-enhanced computed tomography (CECT). Shapiro-Wilk test was performed, and the variables (pre-CRT and post-CRT) presented normal distribution. Pearson's coefficient was used to assess the correlation between volume and density. CRT resulted in a significant decrease in the mean volume of the parotid glands (i.e., original volume reduced by 20.5%; P<0.0001). CRT induced a 30.0% (7 Hounsfield units) increase in density of the right parotid gland and a 24.9% (8 Hounsfield units) increase in density of the left parotid gland (P=0.0198 and P=0.0079, respectively). Changes in morphology and spatial configuration, increased density, and substantial loss of volume of the parotid glands were observed after CRT. There was also a difference in density (P=0.003) in the right-side parotid glands in comparison between xerostomic and nonxerostomic groups of patients. These facts lead to the need for a personalized CRT planning in order to minimize oral complications related to the treatment.
- Differentiation of periapical granuloma from radicular cyst using cone beam computed tomography images texture analysis(2020) ROSA, Catharina Simioni De; BERGAMINI, Mariana Lobo; PALMIERI, Michelle; SARMENTO, Dmitry Jose de Santana; CARVALHO, Marcia Oliveira de; RICARDO, Ana Lucia Franco; HASSEUS, Bengt; JONASSON, Peter; BRAZ-SILVA, Paulo Henrique; COSTA, Andre Luiz FerreiraObjective: This study aimed to investigate the use of texture analysis for characterization of radicular cysts and periapical granulomas and to assess its efficacy to differentiate between both lesions with histological diagnosis. Methods: Cone beam computed tomography (CBCT) images were obtained from 19 patients with 25 periapical lesions (14 radicular cysts and 11 periapical granulomas) confirmed by biopsy. Regions of interest were created in the lesions from which 11 texture parameters were calculated. Spearman's correlation analysis was performed and adjusted with Benjamini-Hochberg false discovery rate procedure (FDR <0.005). Results: The texture parameters used to differentiate the lesions were assessed by using a receiver operating characteristic analysis. Five texture parameters were predictive of lesion differentiation for eight positions: angular second moment; sum of squares; sum of average; contrast; correlation. Conclusion: Texture analysis of CBCT scans distinguishes radicular cysts from periapical granulomas and can be a promising diagnostic tool for periapical lesions. Clinical significance: Texture analysis can be used in diagnostic and treatment monitoring to provide supple-mentary information.
- High-risk human papillomavirus in patients with oral leukoplakia and oral squamous cell carcinoma-A multi-centre study in Sweden, Brazil and Romania(2021) SUNDBERG, Jonas; OHMAN, Jenny; KORYTOWSKA, Magdalena; WALLSTROM, Mats; KJELLER, Goran; ANDERSSON, Maria; HORAL, Peter; LINDH, Magnus; GIGLIO, Daniel; KOVACS, Aniko; SAND, Lars; HIRSCH, Jan-Michael; FERRACINI, Lais Magda Araujo; SOUZA, Ana Carolina Mamana Fernandes de; PARLATESCU, Ioanina; DOBRE, Maria; HINESCU, Mihail-Eugen; BRAZ-SILVA, Paulo Henrique; TOVARU, Serban; HASSEUS, BengtObjectives Although causal associations between oral leukoplakia (OL), oral squamous cell carcinoma (OSCC) and high-risk human papillomavirus (HR-HPV) have been speculated upon in several reports, conclusive evidence has not been presented. This study investigates whether the number of cases of HR-HPV in OL has increased over time and whether the prevalence of HR-HPV-positive OL differs in various parts of the world. Patients and Methods A total of 432 patients with OL from Sweden, Brazil and Romania were analysed. Patients were divided into historical (1992-2002) and contemporary (2011-2017) cohorts from the respective countries. Seventeen patients with OL developed oral squamous cell carcinoma (OSCC). A real-time PCR assay, targeting HPV sub-types 6,11,16,18,31,33,35,39,45,52,56,58 and 59, was performed to detect HR-HPV in patients with OL. Results In the Swedish and Romanian cohorts, none of the investigated HPV sub-types were detected. In the Brazilian cohorts, five patients with OL (3%) were positive for HR-HPV, including four patients from the contemporary cohort (HPV 16, 31, 33) and one from the historical cohort (HPV 11). All the cases of OL that transformed into OSCC were HR-HPV-negative, as were the corresponding tumours. Conclusions In summary, the prevalence of HR-HPV in OL is low in all the tested countries, and the incidence has not changed over time. HR-HPV in OL does not seem to be a driver of oncogenesis.
- Comparison of Immunohistochemistry and DNA Sequencing for BRAF V600E Mutation Detection in Mandibular Ameloblastomas(2021) MARCELINO, Barbara M. R. da Silva; PARISE, Guilherme K.; CANTO, Alan M. do; SASSI, Laurindo M.; SARMENTO, Dmitry J. S.; COSTA, Andre L. F.; HASSEUS, Bengt; KJELLER, Goran; SCHUSSEL, Juliana L.; BRAZ-SILVA, Paulo H.This study aimed to investigate the presence of BRAF V600E mutation in mandibular ameloblastoma by comparing the results of molecular detection and immunohistochemical analysis. A 128 cases of mandibular ameloblastoma and 30 cases of dentigerous cyst (control group) were selected for analysis. Detection of BRAF V600E mutation was performed with immunohistochemistry (IHC) and polymerase chain reaction techniques. Clinico-pathologic data were collected in order to investigate possible associations with the mutation. Of the 128 cases submitted to IHC, 81.2% (108 cases) showed positivity for anti-BRAF V600E antibody, whereas 24 were negative (18.8%). Molecular analysis of the BRAF V600E mutation by polymerase chain reaction was possible in 116 cases due to DNA quality. Of these cases, 96 were positive (82.8%) and 20 negative (17.2%). All cases of dentigerous cyst were negative for BRAF V600E mutation in both techniques. Considering the sequencing as a gold standard method, the receiver operating characteristics curve analysis showed sensitivity of 0.99 and specificity of 1 (area under the curve=0.995, standard error=0.006; P<0.001; 95% confidence interval=0.983 to 1). We also tested the agreement between the techniques by using the Cohen's kappa coefficient, with kappa being 0.97 (P<0.001). IHC is a reliable test for identifying the BRAF V600E mutation in ameloblastomas, presenting advantages such as being more frequently used in surgical pathology laboratories and requiring fewer critical steps for paraffin-embedded tissue compared with molecular biology techniques.
- Inflammatory profile of chronic apical periodontitis: a literature review(2019) BRAZ-SILVA, Paulo Henrique; BERGAMINI, Mariana Lobo; MARDEGAN, Andressa Pinto; ROSA, Catharina Simioni De; HASSEUS, Bengt; JONASSON, PeterApical periodontitis caused by root canal infection is the most frequent pathological lesion in the jaws, mainly manifested as periapical granulomas and cysts. Understanding of the formation and progression of apical periodontitis as well as the identification of inflammatory biomarkers can help increase the knowledge of pathogenic mechanisms, improve the diagnosis and provide support for different therapeutic strategies. The objective of the present article is to review inflammatory biomarkers such as cytokines, chemokines, inflammatory cells, neuropeptides, RANK/RANKL/OPG system and other inflammatory markers and to relate these systems to the development and progression of pathological conditions related to apical periodontitis.
- Patient-reported pain after surgical removal of leukoplakia - an observational 1-year follow-up study(2021) KORYTOWSKA, Magdalena; SCHWAB, Gabriela; GIGLIO, Daniel; HIRSCH, Jan-Michael; HOLMBERG, Erik; KJELLER, Goran; SAND, Lars; WALLSTROM, Mats; OHMAN, Jenny; BRAZ-SILVA, Paulo; HASSEUS, BengtObjective: Oral leukoplakia (OL) presents as a white lesion of the oral mucosa and is not typically associated with the sensation of pain. OL should be surgically removed when possible because it is considered a potentially malignant oral disorder (PMOD). This study assessed the pain sensations experienced by patients in association with the occurrence and surgical treatment of OL. Methods: Inclusion criteria were: a clinical diagnosis of OL; biopsy excision; and observation for at least 12 months in the ORA-LEU-CAN study. At the first visit, all the patients were asked about the occurrence of symptoms within the lesion. Ninety-four subjects were assessed over a period of 1 year. All patients underwent complete removal of OL. The patient cohort was divided into three sub-groups: (i) no pain before excision and at the 1-year follow-up; (ii) pain before excision; and (iii) pain at the 1-year follow-up. Results: Overall, pain was reported by 21.3% of the patients at the study start whereas 13.8% of the patients reported pain 1 year after surgical treatment. Patient-reported pain from the lesion at study inclusion was significantly associated with lesions found on the lateral side of the tongue (p=.002). Pain reported by patients one year after surgery was significantly related to female gender (p=.038) and the presence of epithelial cell dysplasia (p=.022). Conclusion: We conclude that surgical removal of OL results in a low risk of long-term post-surgical pain. However, OL located on the lateral side of the tongue and in OL with dysplasia are more likely to be associated with pain.
- Immunohistochemical analysis of BRAF V600E mutation in ameloblastomas(2019) CANTO, Alan Motta do; MARCELINO, Barbara Michaela Reis da Silva; SCHUSSEL, Juliana Lucena; WASTNER, Bruna F.; SASSI, Laurindo Moacir; CORREA, Luciana; FREITAS, Ronaldo Rodrigues de; HASSEUS, Bengt; KJELLER, Goran; LEMOS JUNIOR, Celso Augusto; BRAZ-SILVA, Paulo HenriqueObjectiveThis study aimed to investigate the presence of BRAF V600E mutation in mandible ameloblastomas by correlating clinical and imaging data on the cases studied.MethodsEighty-four cases diagnosed as mandibular ameloblastoma were selected for analysis. The specimens were submitted to immunohistochemistry for detection of BRAF V600E mutated protein. Clinical-pathological data such as age, gender, tumour size, mandibular location, radiographic aspects, histological type and sub-type, and tumour status were collected. The clinical-pathological parameters were categorised and analysed according to BRAF V600E detection.ResultsOf the 84 patients, 78.6% (66 cases) demonstrated positivity for anti-BRAF V600E antibody, whereas 18 were negative (21.4%). The correlation between BRAF expression and variables showed statistical significances for mandibular location (P=0.0353) and tumour size (P=0.008), whereas no statistical significance was observed for gender, age, radiographic aspect, histological pattern, histological sub-type and tumour status. Multivariate logistic regression revealed a significant risk for BRAF positivity in tumours with posterior mandibular location (OR=7.23, P=0.0451) and size >4cm (OR=7.29, P=0.0150).ConclusionBRAF V600E mutation is common in mandibular ameloblastomas, especially in cases of tumours larger than 4cm and in the posterior region of the mandible. In addition, this mutation can occur regardless of histological type of the tumour, age, gender, radiographic aspect and tumour status.Clinical significanceThe association between clinical-pathologic features and BRAF V600E mutation in ameloblastomas may provide directions for the treatment of this neoplasia. The use of BRAF inhibitors for targeted therapy could lead to an establishment of an alternative compared to the resective surgery.
- EZH2 Expression Correlates With T-Cell Infiltration in Oral Leukoplakia and Predicts Cancer Transformation(2023) GANESH, Divya; DAFAR, Amal; NIKLASSON, Julia; SANDBERG, Ingrid; BRAZ-SILVA, Paulo; SAPKOTA, Dipak; OHMAN, Jenny; GIGLIO, Daniel; HASSEUS, BengtBackground/Aim: The EZH2 complex is involved in cellular proliferation and modulates the immune response in cancer. Less is known about the importance of EZH2 in precancerous lesions such as oral leukoplakia (OL). The aim of the study was to explore the association between EZH2 expression, immune activation, and cancer transformation in OL. Patients and Methods: Analyses were retrospectively performed on nine OL cases that had undergone transformation to oral squamous cell carcinoma (OSCC; OL-ca) and nine that had not undergone transformation (OL-non). EZH2-expressing cells, CD3+ and CD8+ T cells, and CD1a+ Langerhans cells were visualized with immunohistofluorescence and counted. Results: A moderate positive correlation between CD3-and EZH2-expressing and CD8-and EZH2-expressing cells in the epithelium was found (r=0.57, p=0.01; r=0.59, p=0.01). The number of EZH2-expressing cells in the epithelium of OL-ca was significantly higher compared to OL-non (p=0.0002). Cancer - free survival rates differed significantly between patients with EZH2high compared to EZH2low expression (p=0.001). EZH2high expression in OL epithelium was associated with a 13-fold higher risk for developing OSCC (HR=12.8). Conclusion: EZH2 expression in oral epithelium predicts OSCC transformation of OL and correlates with the level of T-cell infiltration.
- COVID-19 salivary signature: diagnostic and research opportunities(2021) SAPKOTA, Dipak; SOLAND, Tine Merete; GALTUNG, Hilde Kanli; SAND, Lars Peter; GIANNECCHINI, Simone; TO, Kelvin K. W.; MENDES-CORREA, Maria Cassia; GIGLIO, Daniel; HASSEUS, Bengt; BRAZ-SILVA, Paulo HenriqueThe COVID-19 (caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)) epidemic started in Wuhan (Hubei Province, China) in mid-December 2019 and quickly spread across the world as a pandemic. As a key to tracing the disease and to implement strategies aimed at breaking the chain of disease transmission, extensive testing for SARS-CoV-2 was suggested. Although nasopharyngeal/oropharyngeal swabs are the most commonly used biological samples for SARS-CoV-2 diagnosis, they have a number of limitations related to sample collection and healthcare personnel safety. In this context, saliva is emerging as a promising alternative to nasopharyngeal/oropharyngeal swabs for COVID-19 diagnosis and monitoring. Saliva collection, being a non-invasive approach with possibility for self-collection, circumvents to a great extent the limitations associated with the use of nasopharyngeal/oropharyngeal swabs. In addition, various salivary biomarkers including the salivary metabolomics offer a high promise to be useful for better understanding of COVID-19 and possibly in the identification of patients with various degrees of severity, including asymptomatic carriers. This review summarises the clinical and scientific basis for the potential use of saliva for COVID-19 diagnosis and disease monitoring. Additionally, we discuss saliva-based biomarkers and their potential clinical and research applications related to COVID-19.
- Lack of direct association between oral mucosal lesions and SARS-CoV-2 in a cohort of patients hospitalised with COVID-19(2022) SCHWAB, Gabriela; PALMIERI, Michelle; ZERBINATI, Rodrigo M.; SARMENTO, Dmitry J. S.; REIS, Thais; ORTEGA, Karem L.; KANO, Italo T.; V, Rafael A. Caixeta; HASSEUS, Bengt; SAPKOTA, Dipak; JUNGES, Roger; GIANNECCHINI, Simone; COSTA, Andre L. F.; JALES, Sumatra M. C. P.; LINDOSO, Jose A. L.; GALLO, Camila Barros; BRAZ-SILVA, Paulo H.Background COVID-19 is a disease affecting various human organs and systems, in which the virus seeks to interact with angiotensin-converting enzyme 2 receptors. These receptors are present in the oral cavity, but the direct relationship between such an interaction and possible oral manifestations of COVID-19 is still unclear. Aim The present study evaluated oral manifestations in a cohort of COVID-19 patients during the period of hospitalisation. Methods In total, 154 patients presenting moderate-to-severe forms of COVID-19 had their oral mucosa examined twice a week until the final outcome, either discharge or death. The oral alterations observed in the patients were grouped into Group 1 (pre-existing conditions and opportunistic oral lesions) and Group 2 (oral mucosal changes related to hospitalization). Results Oral lesions found in the patients of Group 1 are not suggestive of SARS-CoV-2 infection as they are mainly caused by opportunistic infections. On the other hand, oral alterations found in the patients of Group 2 were statistically (P < 0.001) related to intubation and longer period of hospitalisation. Conclusion It is unlikely that ulcerative lesions in the oral cavity are a direct manifestation of SARS-CoV-2 or a marker of COVID-19 progression.