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OBJECTIVES: Chemoprevention can be a treatment for potentially malignant lesions (PMLs). We aimed to evaluate whether artemisinin (ART) and cisplatin (CSP) are associated with apoptosis and immunogenic cell death (ICD) in vitro, using oral leukoplakia (OL) and oral squamous cell carcinoma (OSCC) cell lines, and whether these compounds prevent OL progression in vivo. METHODS: Normal keratinocytes (HaCat), Dysplastic oral cells (DOK), and oral squamous cell carcinoma (SCC-180) cell lines were treated with ART, CSP, and ART + CSP to analyze cytotoxicity, genotoxicity, cell migration, and increased expression of proteins related to apoptosis and ICD. Additionally, 41 mice were induced with OL using 4NQO, treated with ART and CSP, and their tongues were histologically analyzed. RESULTS: In vitro, CSP and CSP + ART showed dose-dependent cytotoxicity and reduced SCC-180 migration. No treatment was genotoxic, and none induced expression of proteins related to apoptosis and ICD; CSP considerably reduced High-mobility group box-1 (HMGB-1) protein expression in SCC-180. In vivo, there was a delay in OL progression with ART and CSP treatment; however, by the 16th week, only CSP prevented progression to OSCC. CONCLUSION: Expression of proteins related to ICD and apoptosis did not increase with treatments, and CSP was shown to reduce immunogenic pathways in SCC-180, while reducing cell migration. ART did not prevent the malignant progression of OL in vivo; CSP did despite significant adverse effects.
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Apoptose , Artemisininas , Movimento Celular , Cisplatino , Progressão da Doença , Leucoplasia Oral , Neoplasias Bucais , Artemisininas/farmacologia , Animais , Leucoplasia Oral/patologia , Leucoplasia Oral/tratamento farmacológico , Humanos , Cisplatino/farmacologia , Camundongos , Neoplasias Bucais/patologia , Neoplasias Bucais/tratamento farmacológico , Apoptose/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/patologia , Linhagem Celular Tumoral , Proteína HMGB1/metabolismo , Antineoplásicos/farmacologiaRESUMO
OBJECTIVE: This study aims to analyze the prevalence of Candida spp. colonization in oral leukoplakia and oral lichen planus lesions, verify the influence of systemic and local factors, besides identify and determine the in vitro antifungal susceptibility profile of Candida species. MATERIALS AND METHODS: Samples were collected by swabbing from oral lesions and healthy mucosa and cultured on Sabouraud Dextrose and CHROMagar® Candida plates. Species identification was confirmed with MALDI-TOF MS analysis. RESULTS: Candida spp. was found in 36.8% of cases of oral leukoplakia and 18.2% of cases of oral lichen planus. Candida albicans was the only species found in oral lichen planus lesions (n = 2, 100%) and the most prevalent in oral leukoplakia (n = 5, 76.4%). Among the non-albicans Candida species found in oral leukoplakia were C. parapsilosis (n = 2, 25.5%) and C. tropicalis (n = 1, 14.1%). Candida isolates were susceptible to all antifungals tested. CONCLUSION: C. albicans was the most commonly found species in the studied lesions. No correlation was found between systemic and local factors with positive cases of oral lichen planus. However, smoking and alcohol consumption may be associated with positive cases of oral leukoplakia, especially the non-homogeneous clinical form. In addition, there is a possible predisposition to associated Candida colonization in cases of epithelial dysplasia found in oral leukoplakia. The antifungal medications tested showed excellent efficacy against isolates.
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Antifúngicos , Candida , Leucoplasia Oral , Líquen Plano Bucal , Testes de Sensibilidade Microbiana , Humanos , Líquen Plano Bucal/microbiologia , Líquen Plano Bucal/patologia , Leucoplasia Oral/microbiologia , Leucoplasia Oral/patologia , Candida/efeitos dos fármacos , Candida/isolamento & purificação , Candida/classificação , Masculino , Pessoa de Meia-Idade , Feminino , Antifúngicos/farmacologia , Adulto , Idoso , Candidíase Bucal/microbiologia , Adulto Jovem , PrevalênciaRESUMO
Proliferative verrucous leukoplakia (PVL) is a non-homogenous type of oral leukoplakia, characterized by multifocal white plaques, propensity to recur after treatment, with strong tendency towards malignant transformation. Interestingly, some studies show that, at initial stages, PVL may resemble oral lichen planus (OLP), potentially leading to misdiagnosis. A 52-year-old woman, with a previous OLP diagnosis, was referred to our service for implant installation and follow-up of OLP lesions. After clinicopathological re-evaluation, a diagnosis of PVL (early stage) was made, and a maxillary full-arch implant-supported prosthesis supported by implants was installed. After 6 years of follow-up, the patient developed squamous cell carcinoma around the implants. The current case emphasizes that PVL patients with oral lesions suggesting peri-implantitis or peri-implant mucositis deserve a more meticulous investigation.
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Prótese Dentária Fixada por Implante , Leucoplasia Oral , Líquen Plano Bucal , Humanos , Feminino , Pessoa de Meia-Idade , Líquen Plano Bucal/diagnóstico , Líquen Plano Bucal/patologia , Leucoplasia Oral/diagnóstico , Leucoplasia Oral/patologia , Diagnóstico Diferencial , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/diagnóstico , Progressão da Doença , Peri-Implantite/diagnóstico , SeguimentosRESUMO
BACKGROUND: This study evaluated the presence of Epstein-Barr virus type 1 (EBV-1) DNA in patients living with HIV, before and after three different topical therapy protocols for oral hairy leukoplakia (OHL). METHODS: The sample consisted of five patients treated with topical solution of 25% podophyllin resin; six with 25% podophyllin resin plus 5% acyclovir cream; and four with 25% podophyllin resin plus 1% penciclovir cream. DNA was extracted from OHL scrapings and amplified by the PCR using specific primers for EBV-1 (EBNA-1). RESULTS: Clinical healing of OHL lesions was observed across all treatment groups over time. At baseline, EBNA-1 was detected in all OHL lesions. After treatment, OHL samples from three patients treated with 25% podophyllin resin plus 5% acyclovir cream and from one patient treated with 25% podophyllin resin plus 1% penciclovir cream exhibited negative EBNA-1 viral gene encoding. Despite the clinical resolution of OHL, 11 patients (73.3%) showed EBNA-1 positivity immediately after the lesion disappeared. Three patients (20%) treated with podophyllin resin displayed both EBNA-1 positivity and a recurrence of OHL, in contrast to no recurrence in the other two groups. CONCLUSIONS: These findings suggest potential associations between treatment formulations, EBNA-1 persistence, and the recurrence of OHL lesions.
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Aciclovir , Administração Tópica , Antivirais , DNA Viral , Infecções por Vírus Epstein-Barr , Herpesvirus Humano 4 , Leucoplasia Pilosa , Humanos , Feminino , Masculino , Antivirais/uso terapêutico , Antivirais/administração & dosagem , Leucoplasia Pilosa/tratamento farmacológico , Leucoplasia Pilosa/virologia , Herpesvirus Humano 4/genética , Herpesvirus Humano 4/isolamento & purificação , Aciclovir/uso terapêutico , Aciclovir/administração & dosagem , Pessoa de Meia-Idade , DNA Viral/análise , Infecções por Vírus Epstein-Barr/tratamento farmacológico , Infecções por Vírus Epstein-Barr/virologia , Adulto , Podofilina/uso terapêutico , Podofilina/administração & dosagem , Resultado do Tratamento , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Reação em Cadeia da Polimerase , Guanina/análogos & derivados , Guanina/uso terapêutico , Guanina/administração & dosagemRESUMO
Oral leukoplakia is the most frequent and potentially malignant lesion of the oral cavity. Although dysplasia grading remains the main factor for risk assessment, challenges persist in determining the exact risk of transformation, and the literature has focused on studying alternative biomarkers. The interaction between dysplastic epithelial cells and the microenvironment starts early, and the communication is mainly mediated by lymphocytes, inflammatory factors, fibroblasts, and the extracellular matrix, leading to dysplastic progression. Leukoplakia-infiltrating leukocytes (LILs) and leukoplakia-associated fibroblasts (LAFs) play crucial roles in the dysplastic microenvironment. The immune response is related to intraepithelial T lymphocyte infiltration, mechanisms of immunosuppression coordinated by regulatory T cells, M2 macrophage polarization, and increased numbers of Langerhans cells; in contrast, fibroblastic and extracellular matrix factors are associated with increased numbers of pro-tumorigenic myofibroblasts, increased expression of metalloproteinases vs. decreased expression of TIMPs, and increased expression of chemokines and other inflammatory mediators. The microenvironment offers insights into the progression of leukoplakia to carcinoma, and understanding the complexity of the oral microenvironment in potentially malignant diseases aids in determining the risk of malignant transformation and proposing new therapeutic alternatives.
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BACKGROUND: To investigate the association between tooth loss and oral potentially malignant disorders and oral squamous cell carcinoma, focusing on epidemiological factors and genetic variants. METHODS: Case-control study, including histologically confirmed oral potentially malignant disorders and oral squamous cell carcinoma cases and healthy controls. Unadjusted and adjusted odds ratios for this association were calculated. Single-nucleotides polymorphisms were tested for individuals with and without missing teeth. RESULTS: Case individuals were more edentulous while controls had fewer missing teeth (p = 0.006). There was an increased risk for the outcomes associated with edentulism (OR = 6.95, p = 0.000), even after adjustments for educational level (OR = 4.7, p = 0.034) and smoking habits (OR = 5.01, p = 0.022). Among individuals with tooth loss, rs1533767 (WNT11), rs3923087, and rs11867417 (AXIN2) were associated with the outcomes (OR = 1.67, p = 0.03, OR = 0.53, p = 0.05, and OR = 0.42, p = 0.00, respectively). CONCLUSIONS: Tooth loss could increase the risk for oral potentially malignant disorders and oral squamous cell carcinoma.
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Carcinoma de Células Escamosas , Neoplasias Bucais , Perda de Dente , Humanos , Neoplasias Bucais/genética , Masculino , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/epidemiologia , Feminino , Estudos de Casos e Controles , Pessoa de Meia-Idade , Perda de Dente/epidemiologia , Idoso , Polimorfismo de Nucleotídeo Único , Adulto , Predisposição Genética para Doença , Fatores de Risco , Lesões Pré-Cancerosas/genética , Lesões Pré-Cancerosas/patologia , Interação Gene-AmbienteRESUMO
Novos fármacos, como a artemisinina (ART), podem ser promissores no tratamento de lesões potencialmente malignas (LPM) e podem ser úteis quando usados em associação com outros quimioterápicos, especialmente na redução dos seus efeitos colaterais. A leucoplasia oral (LO) é a LPM mais comum da cavidade bucal e, pode evoluir para um carcinoma de células escamosas oral (CCEO). Não há terapia para evitar a sua transformação maligna, a quimioprevenção pode iniciar a morte celular imunogênica (MCI) que ativa o sistema imunológico para que reconheça e elimine as células malignas ou pré-malignas, sendo um potencial tratamento para as LPM. O presente estudo objetivou avaliar se a ART e a cisplatina (CSP) associadas ou não seriam capazes de induzir a MCI em linhagens celulares de LO (DOK) e CCEO SCC180). Material e métodos: As linhagens celulares HaCat (controle), DOK e SCC-180 foram tratadas por ART e CSP de forma combinada ou isolada, a fim de analisar a citotoxicidade e a genotoxicidade destes fármacos, além da capacidade destes em reduzir a migração celular e, se os compostos seriam capazes de induzir a expressão da proteína box de alta mobilidade (HGMB-1), caspase 3, 8, 9, e Calreticulina (CALR). Resultados: Em todas as linhagens celulares a CSP e CSP+ART causaram uma resposta dose dependente, apresentando maior citotoxicidade com doses mais altas, o que não foi observado com a ART. A formação de micronúcleos não foi observada no teste de genotoxicidade. A taxa de migração foi reduzida com as concentrações de IC50 de CSP e ART+CSP para as células de CCEO. Não foram encontradas expressões significativas de proteínas relacionadas à MCI ou apoptose nas linhagens de LO e CCEO, tratadas com ART, CSP ou ART+CSP, indicando que outro tipo de morte celular possa ter ocorrido. Conclusão: A MCI e a apoptose não foram evidenciadas como forma de morte celular após as linhagens de LO e CCEO receberem tratamentos com ART, CSP e a associação de ambas. Efeitos genotóxicos não foram observados nas doses testadas. O tratamento de CSP e ART+CSP foi capaz de reduzir a migração de células de CCEO. Também concluímos que novos estudos são necessários para elucidar se a ART e CSP podem ocasionar a MCI ou apoptose em linhagens celulares de LO e CCEO (AU)
New drugs, such as artemisinin (ART), may be promising in the treatment of potentially malignant lesions (PML) and may be useful when used in combination with other chemotherapy drugs, especially in reducing their side effects. Oral leukoplakia (OL) is the most common LPM of the oral cavity and can progress to oral squamous cell carcinoma (OSCC). There is no therapy to prevent its malignant transformation, chemoprevention can initiate immunogenic cell death (ICM) that activates the immune system to recognize and eliminate malignant or pre-malignant cells, being a potential treatment for LPM. The present study aimed to evaluate whether or not ART and cisplatin (CSP) combined would be capable of inducing MCI in LO (DOK) and CCEO SCC-180) cell lines. Material and methods: HaCat (control), DOK and SCC-180 cell lines were treated by ART and CSP in combination or alone, in order to analyze the cytotoxicity and genotoxicity of these drugs, in addition to their ability to reduce cell and, whether the compounds would be able to induce the expression of high mobility box protein (HGMB-1), caspase 3, 8, 9, and Calreticulin (CALR). Results: In cytotoxicity at higher doses, which was not observed with ART. The formation of micronuclei was not observed in the genotoxicity test. The migration rate was reduced with the IC50 concentrations of CSP and ART+CSP for OSCC cells. No significant expressions of proteins related to MCI or apoptosis were found in the LO and CCEO lines, treated with ART, CSP or ART+CSP, indicating that another type of cell death may have occurred. Conclusion: MCI and apoptosis were not evidenced as a form of cell death after the LO and CCEO lines received treatments with ART, CSP and the combination of both. Genotoxic effects were not observed at the doses tested. CSP and ART+CSP treatment was able to reduce OSCC cell migration. We also conclude that new studies are necessary to elucidate whether ART and CSP can cause MCI or apoptosis in LO and CCEO cell lines.(AU)
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Leucoplasia Oral , Imunomodulação , Carcinoma de Células Escamosas de Cabeça e Pescoço , Morte Celular Imunogênica , Células Apresentadoras de AntígenosRESUMO
Introducción: La leucoplasia es la lesión potencialmente maligna más común de la mucosa bucal; el consumo de tabaco es el principal factor etiológico; se presentan distintos grados de displasia epitelial. Su estudio permite conocer mejor las manifestaciones clínicas e histopatológicas de esta enfermedad. Objetivo: Caracterizar clínica e histopatológicamente la leucoplasia homogénea bucal en pacientes fumadores de tabaco. Métodos: Se realizó un estudio descriptivo y transversal. El universo estuvo compuesto por 75 pacientes fumadores de tabaco y cigarros, atendidos en la consulta estomatológica del Policlínico de Especialidades del Hospital Clínico-Quirúrgico Saturnino Lora Torres de Santiago de Cuba. Mediante el examen clínico e histopatológico se diagnosticó leucoplasia homogénea bucal. Para la recolección del dato primario se confeccionó un modelo con las siguientes variables: grupo de edad, sexo, diagnóstico clínico, tiempo en el hábito de fumar, localización anatómica y estudio histopatológico de la enfermedad. Resultados: En la casuística prevaleció el sexo masculino (58,6 por ciento) y el grupo etario de 60 años y más (41,3 por ciento); la hiperparaqueratosis (64,0 por ciento), el infiltrado inflamatorio crónico ligero (60,0 por ciento) y la displasia epitelial leve (73,3 por ciento) fueron las alteraciones hísticas más comunes en fumadores con 21 y más años. La hipercromasia del núcleo (100,0 por ciento) y el pleomorfismo nuclear (96,80 por ciento) resultaron los cambios celulares más prominentes. Las alteraciones de los clavos interpapilares (92,0 por ciento), la hiperplasia del estrato basal (88,9 por ciento) y la pérdida de la polaridad (87,3 por ciento) resultaron los signos displásicos tisulares más significativos en la leucoplasia bucal y la mucosa de carrillo (40,0 por ciento) el sitio anatómico de mayor ocurrencia de lesiones. Conclusiones: Todos los pacientes fumadores de tabaco y cigarro presentaron, clínicamente, lesiones leucoplásicas bucales, confirmadas por el estudio histopatológico; el sexo masculino y el grupo de 60 y más años son los de mayor afectación. La hiperparaqueratosis, el infiltrado inflamatorio crónico ligero y la displasia epitelial leve fueron los de mayor predominio; la hipercromasia del núcleo y el pleomorfismo nuclear fueron los cambios celulares más prominentes. En el tejido displásico epitelial prevalecieron las alteraciones de los clavos interpapilares, la hiperplasia del estrato basal y la pérdida de la polaridad y el sitio más afectado, la mucosa de carrillo(AU)
Introduction: Leukoplakia is the most common potentially malignant lesion of the buccal mucosa; tobacco use is the main etiological factor; different degrees of epithelial dysplasia are present. Its study allows a better understanding of the clinical and histopathological manifestations of this disease. Objective: To clinically and histopathologically characterize homogeneous buccal leukoplakia in patients who smoke tobacco. Methods: A descriptive and cross-sectional study was performed. The universe was composed of 75 patients who smoked tobacco and cigars, attended in the stomatological consultation of the Specialties Polyclinic of the Clinical-Surgical Hospital Saturnino Lora Torres of Santiago de Cuba. By means of clinical and histopathological examination, homogeneous buccal leukoplakia was diagnosed. For the collection of the primary data, a model was made with the following variables: age group, sex, clinical diagnosis, time in smoking habit, anatomical location and histopathological study of the disease. Results: Male sex (58.6 percent)) and age group 60 years and older (41.3 percent) prevailed in the casuistry; hyperkeratosis (64.0 percent)), mild chronic inflammatory infiltrate (60.0 percent)) and mild epithelial dysplasia (73.3 percent)) were the most common histopathological alterations in smokers aged 21 years and older. Hyperchromasia of the nucleus (100.0 percent)) and nuclear pleomorphism (96.80 percent)) were the most prominent cellular changes. Interpapillary nail alterations (92.0 percent)), stratum basale hyperplasia (88.9 percent)) and loss of polarity (87.3 percent)) resulted the most significant tissue dysplastic signs in buccal leukoplakia and cheek mucosa (40.0 percent)) the anatomical site of highest occurrence of lesions. Conclusions: All tobacco and cigarette smoking patients presented, clinically, buccal leukoplastic lesions, confirmed by histopathological study; male sex and the 60 and older age group are the most affected. Hyperparapokeratosis, mild chronic inflammatory infiltrate and mild epithelial dysplasia were the most predominant; hyperchromasia of the nucleus and nuclear pleomorphism were the most prominent cellular changes. In the epithelial dysplastic tissue, interpapillary nail alterations, hyperplasia of the stratum basale and loss of polarity prevailed and the most affected site, the cheek mucosa(AU)
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Humanos , Masculino , Pessoa de Meia-Idade , Leucoplasia Oral , Diagnóstico Clínico , Fumar Cigarros , Fumantes , Estudos TransversaisRESUMO
Abstract The objective of the present study was to investigate the frequency of oral leukoplakia and oral erythroplakia among young patients from three Brazilian reference centers in Oral and Maxillofacial Pathology. A retrospective study was carried out from 2011 to 2021 on 861 patients diagnosed with oral leukoplakia and oral erythroplakia. Demographic and clinicopathological data were evaluated. Fisher's exact test was used to evaluate the association among sex, age, anatomical location, and histopathological diagnosis. A total of 83 (9.64%) cases involved young patients (aged <40 years). Among these, biopsy records were included in 31 (37.34%) cases, all of which received a clinical diagnosis of oral leukoplakia. Seventeen (54.84%) patients were female, mostly in their fourth decade of life (n = 22/70.97%), and their mean age at diagnosis was 32.61(± 5.21) years. Among informed cases, seven (22.58%) patients were smokers. The lateral border of the tongue (n = 9/29.03%) was the most affected site. In 13 (41.94%) cases, oral leukoplakias showed a homogeneous appearance. The mean size of the lesions was 1.47 cm (0.2-3.0 cm) and the mean time of disease progression was 64.37 (± 65.90) months. The histopathological analysis showed that 11 cases (35.48%) exhibited some degree of epithelial dysplasia. Acanthosis and/or hyperkeratosis were observed in 20 cases (64.52%). No significant associations were observed between sex and anatomical location, age and anatomical location, nor between sex and histological diagnosis (p > 0.05). Oral leukoplakia and oral erythroplakia are uncommon diseases in young patients. In this population, oral leukoplakia shows a slight predilection for women aged between 30 and 39 years.
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El cáncer oral representa un grave problema de salud a nivel mundial debido a su importante morbilidad y mortalidad. Ocupa la sexta causa de muerte por cáncer y tienen una supervivencia mundial a cinco años cercana a 50%, en gran parte debido a la falta de su reconocimiento en estadios iniciales por parte de los pacientes y de los mismos profesionales de la salud, lo que ocasiona un grave retraso en su diagnóstico y tratamiento. Se presenta el caso de una mujer de 64 años de edad con úlceras de larga evolución en la cavidad oral y quien acude a múltiples profesionales de salud sin ser diagnosticada en las fases iniciales de la enfermedad; acude a la Universidad Autónoma de Tlaxcala en donde se diagnostica carcinoma oral de células escamosas en el maxilar. En el presente artículo se hace énfasis en el reconocimiento de signos clínicos y factores precipitantes que puedan generar sospecha de un crecimiento maligno y así concientizar a los profesionales de la salud para promover la prevención (AU)
Oral cancer represents a serious health problem worldwide due to its significant morbidity and mortality, it is the sixth leading cause of cancer death and has a global 5-year survival rate of 50%, largely due to the lack of recognition in early stages by patients and health professionals themselves, which causes a serious delay in diagnosis and treatment. We present the case of a 64-year-old woman with long-standing ulcers in the oral cavity who went to multiple health professionals without being diagnosed in the initial stages of the disease. She went to the Autonomous University of Tlaxcala where oral squamous cell carcinoma (OSCC) in the maxilla was diagnosed. This article emphasizes the recognition of clinical signs and precipitating factors that may generate suspicion of malignant growth and thus raise awareness among health professionals to promote prevention (AU)
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Humanos , Feminino , Pessoa de Meia-Idade , Neoplasias Palatinas , Faculdades de Odontologia , Sinais e Sintomas , Causalidade , Úlceras Orais , MéxicoRESUMO
OBJECTIVE: To determine the frequency of oral squamous cell carcinoma (OSCC) associated or not with oral potentially malignant disorders (OPMD), and the epidemiological profile and traditional risk factors in Latin America. METHODS: A retrospective observational study was conducted in 17 Latin American centres. There were included cases of OSCC, analysing age, gender, OSCC and their association with previous OPMD. Clinicopathological variables were retrieved. The condition of sequential-OSCC versus OSCC-de novo (OSCC-dn) was analysed concerning the aforementioned variables. Quantitative variables were analysed using Student's t-test, and qualitative variables with chi-square. RESULTS: In total, 2705 OSCC were included with a mean age of 62.8 years old. 55.8% were men. 53.75% of the patients were smokers and 38% were common drinkers. The lateral tongue border was the most affected site (24.65%). There were regional variations in OPMD, being leukoplakia the most frequent. Of the overall 2705 OSCC cases, 81.4% corresponded to OSCC-dn, while s-OSCC were 18.6%. Regarding lip vermillion SCC, 35.7% corresponded to de novo lip SCC and 64.3% were associated with previous OPMD. CONCLUSIONS: In Latin America, OSCC-dn seems to be more frequent with regional variations of some clinical and histopathological features. Further prospective studies are needed to analyse this phenomenon.
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BACKGROUND: Dysplasia grading systems for oral epithelial dysplasia are a source of disagreement among pathologists. Therefore, machine learning approaches are being developed to mitigate this issue. METHODS: This cross-sectional study included a cohort of 82 patients with oral potentially malignant disorders and correspondent 98 hematoxylin and eosin-stained whole slide images with biopsied-proven dysplasia. All whole-slide images were manually annotated based on the binary system for oral epithelial dysplasia. The annotated regions of interest were segmented and fragmented into small patches and non-randomly sampled into training/validation and test subsets. The training/validation data were color augmented, resulting in a total of 81,786 patches for training. The held-out independent test set enrolled a total of 4,486 patches. Seven state-of-the-art convolutional neural networks were trained, validated, and tested with the same dataset. RESULTS: The models presented a high learning rate, yet very low generalization potential. At the model development, VGG16 performed the best, but with massive overfitting. In the test set, VGG16 presented the best accuracy, sensitivity, specificity, and area under the curve (62%, 62%, 66%, and 65%, respectively), associated with the higher loss among all Convolutional Neural Networks (CNNs) tested. EfficientB0 has comparable metrics and the lowest loss among all convolutional neural networks, being a great candidate for further studies. CONCLUSION: The models were not able to generalize enough to be applied in real-life datasets due to an overlapping of features between the two classes (i.e., high risk and low risk of malignization).
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Aprendizado Profundo , Humanos , Estudos Transversais , Redes Neurais de Computação , Aprendizado de Máquina , BiópsiaRESUMO
Current research highlighted the importance to recognize feasible biomarkers for early diagnoses and treatment in oral cancer. Our study analyzed the expression and spatial distribution of ALDH1A1, FGFR2, caspase-3, and CD44 in Oral Squamous Cell Carcinoma (OSCC) and leukoplakia with and without oral mucosal dysplasia. Paraffin-embedded samples of OSCC (n=5), leukoplakia with (n=5) and without (n=5) dysplasia obtained by incisional biopsies were processed using conventional histochemical techniques. Immunohistochemistry was performed using antibodies against ALDH1A1, FGFR2, caspase-3, and CD44. Images of the immunohistochemically stained tissue sections were analyzed according to the intensity of the immunostaining of each marker and classified in Scores. The Kruskal- Wallis test was performed (p≤0.05). Our results demonstrated a statically difference in the expression of all immunomarkers between OSCC and leukoplakia without dysplasia, being more significant in FGFR2 and ALDH1A1. Within the limitations of this study, our data showed that all biomarkers were overexpressed in OSCC and leukoplakia with oral mucosa dysplasia, suggesting that the presence of dysplasia is a significant clinic-pathologic predictor for malignant transformation.
La actual evidencia científica enfatiza la importancia de reconocer biomarcadores viables para el diagnóstico y tratamiento temprano del cáncer oral. Nuestro estudio piloto analizó la expresión y distribución espacial de ALDH1A1, FGFR2, caspasa-3 y CD44 en carcinoma oral de células escamosas (COCE) y en leucoplasia con o sin displasia de la mucosa oral. Las muestras incluidas en parafina de COCE (n=5), con (n=5) y sin (n=5) displasia fueron obtenidas mediante biopsias incisionales, las cuales se procesaron utilizando técnicas histoquímicas convencionales. El análisis inmunohistoquímico se realizó utilizando anticuerpos contra ALDH1A1, FGFR2, caspasa-3 y CD44. Las imágenes de las secciones de cada muestra fueron analizadas según la intensidad de inmunoexpresión de cada marcador y se clasificaron en diferentes escalas (scores). Se realizó la prueba de Kruskal-Wallis (valores de p<0,05). Nuestros resultados demostraron una diferencia estadística en la expresión de todos los inmunomarcadores entre COCE y las muestras con leucoplasia sin displasia, siendo más significativa en FGFR2 y ALDH1A1. Considerando las limitaciones de este estudio, los datos sugieren que la presencia de displasia en la mucosa oral es un importante predictor clínico-patológico de transformación maligna.
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Proliferative verrucous leukoplakia (PVL) is an oral potentially malignant disorder associated with high risk of malignant transformation. Currently, there is no treatment available, and restrictive follow-up of patients is crucial for a better prognosis. Oral leukoplakia (OL) shares some clinical and microscopic features with PVL but exhibits different clinical manifestations and a lower rate of malignant transformation. This study aimed to investigate the proteomic profile of PVL in tissue and saliva samples to identify potential diagnostic biomarkers with therapeutic implications. Tissue and saliva samples obtained from patients with PVL were compared with those from patients with oral OL and controls. Label-free liquid chromatography with tandem mass spectrometry was employed, followed by qualitative and quantitative analyses, to identify differentially expressed proteins. Potential biomarkers were identified and further validated using immunohistochemistry. Staining intensity scan analyses were performed on tissue samples from patients with PVL, patients with OL, and controls from Brazil, Spain, and Finland. The study revealed differences in the immune system, cell cycle, DNA regulation, apoptosis pathways, and the whole proteome of PVL samples. In addition, liquid chromatography with tandem mass spectrometry analyses showed that calreticulin (CALR), receptor of activated protein C kinase 1 (RACK1), and 14-3-3 Tau-protein (YWHAQ) were highly expressed in PVL samples. Immunohistochemistry validation confirmed increased CARL expression in PVL compared with OL. Conversely, RACK1 and YWHA were highly expressed in oral potentially malignant disorder compared to the control group. Furthermore, significant differences in CALR and RACK1 expression were observed in the OL group when comparing samples with and without oral epithelial dysplasia, unlike the PVL. This research provides insights into the molecular mechanisms underlying these conditions and highlights potential targets for future diagnostic and therapeutic approaches.
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Neoplasias Bucais , Humanos , Neoplasias Bucais/patologia , Proteômica , Espectrometria de Massas em Tandem , Leucoplasia Oral/diagnóstico , Leucoplasia Oral/patologia , Leucoplasia Oral/terapia , Biomarcadores , Cromatografia Líquida , Transformação Celular Neoplásica/patologiaRESUMO
Oral potentially malignant disorders have the potential to transform into oral cancer. Oral leukoplakia is a prevalent OPMD with a 9.8% malignant transformation rate. The standard management for OL involves surgical excision, but its efficacy in preventing clinical recurrence and malignant transformation is limited. Therefore, alternative strategies such as chemoprevention modalities have emerged as a promising approach to inhibit the carcinogenesis process. The aim of this review was to identify human studies that investigated the effectiveness of chemopreventive agents in preventing the progression of oral leukoplakia and to provide guidance for future research. Several systemic and topical agents have been evaluated for their potential chemopreventive effects in oral leukoplakia. Systemic agents that have been investigated include vitamin A, lycopene, celecoxib, green tea extract, ZengShengPing, Bowman Birk inhibitor, beta-carotene, curcumin, erlotinib, and metformin. In addition, topical agents tested include bleomycin, isotretinoin, ONYX-015 mouthwash, ketorolac, and dried black raspberry. Despite numerous agents that have already been tested, evidence supporting their effectiveness is limited. To improve the search for an ideal chemopreventive agent for oral leukoplakia, we propose several strategies that can be implemented. Oral leukoplakia chemoprevention presents a promising opportunity for decreasing the incidence of oral cancer. Identifying new chemopreventive agents and biomarkers for predicting treatment response should be a focus of future research.
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PURPOSE: High-power diode laser emerges as a promising approach to the treatment of oral leukoplakia (OL); however, its short- and long-term effects have been barely explored. This study evaluated the postoperative endpoints and the recurrence rate of high-power diode laser treatment in a well-defined series of patients with OL. METHODS: A prospective analysis was performed on 22 individuals comprising 31 OL. The lesions were irradiated using the following protocol: Indium-Gallium-Arsenide diode laser, 808 nm, continuous-wave mode, 1.5-2.0 W, 780.0 ± 225.1 J, and 477.1 ± 131.8 s. Postoperative pain was assessed with a visual analog scale at three endpoints. Clinical follow-up was performed on all patients and the Kaplan-Meier test was used to analyze the probability of recurrence. RESULTS: The series consisted mostly of women (72.7%) with a mean age of 62.8 years. A single laser session was performed in 77.4% of cases. The median score on the scale that assessed pain on the 1st, 14th and 42nd postoperative day was 4, 1, and 0, respectively. The mean follow-up period per lesion was 28.6 months (range: 2-53 months). A complete response was observed in 93.5% of OL cases, while 6.5% had recurrence. The probability of recurrence at 39 months was 6.7%. No patient experienced malignant transformation. CONCLUSION: High-power diode laser for the treatment of OL is safe and effective during the trans- and postoperative period. These findings represent an alternative approach to the management of OL, mainly because a low recurrence rate was observed.
Assuntos
Lasers Semicondutores , Leucoplasia Oral , Humanos , Feminino , Pessoa de Meia-Idade , Lasers Semicondutores/uso terapêutico , Leucoplasia Oral/radioterapia , Leucoplasia Oral/cirurgia , Leucoplasia Oral/patologia , Dor Pós-Operatória , Transformação Celular Neoplásica , Medição da DorRESUMO
Introdução:as desordens orais potencialmente malignas (DOPMs) são condições que podem preceder o aparecimento do câncer em cavidade bucal. Objetivo: descrever os principais aspectos clínicos, histológicos e tratamento da leucoplasia, eritroplasia, queilite actínica e líquen plano oral. Metodologia: trata-se de uma revisão da literatura atual, em que foram consultados artigos nas bases do MEDLINE/PUBMED e Biblioteca Virtual em Saúde, publicados nos últimos 10 anos. Os descritores foram localizados usando o vocabulário controlado do MeSH, sendo eles: Leukoplakia; Erythroplakia, Actinic cheilitis, Oral lichen planus, Diagnosis, Therapeutics. Resultados: asapresentações clínicas das DOPMs são diversas. A leucoplasia é a mais comum e deve ser distinguida da leucoplasia verrucosa proliferativa que tem uma apresentação clínica generalizada e uma tendência à recorrência após a excisão; a eritroplasia, embora rara, tem maior chance de malignização. A queilite actínica acomete com frequência o lábio inferior, tem forte relação com exposição solar e pode progredir para o carcinoma escamocelular labial; o líquen plano oral tem uma variedade de apresentações clínicas, sendo a forma reticular a mais comum. O tipo erosivo, atrófico ou bolhoso é acompanhado de sintomatologia dolorosa variável. A biópsia é essencial para confirmar a suspeita clínica das DOPMs e o encaminhamento oportuno para um especialista é indicado. Conclusão: as DOPMs podem ser encontradas durante o exame bucal, possibilitando assim, o diagnóstico precoce, e o correto encaminhamento a um especialista e a intervenção adequada, podendo reduzir a taxa de progressão dessas condições para câncer.
Introduction: Oral Potentially Malignant Disorders (OPMDs) are conditions that may precede the onset of cancer in the oral cavity. Objective: To describe the main clinical features, histological aspects and treatment of leukoplakia, erythroplakia, actinic cheilitis and oral lichen planus. Methodology: this is a review of the current literature, in which articles in the databases of MEDLINE/PUBMED and the Virtual Health Library, published in the last 10 years, were consulted. The descriptors were located using the MeSH controlled vocabulary, namely: Leukoplakia; Erythroplakia, Actinic cheilitis, Oral lichen planus, Diagnosis, Therapeutics. Results:the clinical presentations of OPMDs are diverse. Leukoplakia is the most common and must be distinguished from proliferative verrucous leukoplakia which has a generalized clinical presentation and a tendency to reoccur after excision; erythroplakia, although rare, has a greater chance of becoming malignant. Actinic cheilitis frequently affects the lower lip, is strongly related to sun exposure and can progress to labial squamous cell carcinoma; oral lichen planus has a variety of clinical presentations, with the reticular form being the most common. The erosive, atrophic or bullous type is accompanied by different levels of pain. Biopsy is essential to confirm the clinical suspicion of OPMDs and timely referral to a specialist is indicated. Conclusion: OPMDs can be found during oral examination, thus enabling early diagnosis, correct referral to a specialist and appropriate intervention, which may reduce the rate of progression of these conditions to cancer.
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Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Neoplasias Bucais , Queilite , Líquen Plano Bucal , Eritroplasia , LeucoplasiaRESUMO
El síndrome de Jadassohn-Lewandowsky o paquioniquia congénita tipo 1 pertenece al grupo de las enfermedades raras. A nivel mundial se han descrito hasta la fecha menos de mil casos y el que ahora se publica constituye el primer reporte en la edad pediátrica en Cuba. Es un paciente masculino, de siete años de edad ingresado en el Servicio de Clínicas Pediátricas del Hospital Pediátrico Provincial de Holguín con antecedentes de uñas amarillas e hipertróficas desde los nueve meses de edad. Al examen físico se constató la presencia de distrofia ungueal hipertrófica en las 20 uñas, queratosis folicular en codos, manos y miembros inferiores, queratodermia plantar focal y leucoqueratosis oral. Se identificó un patrón de herencia autosómico dominante. Basado en las características fenotípicas y los antecedentes familiares se clasificó el caso presentado como paquioniquia congénita tipo 1, para la cual aún no existe cura y la terapia génica se encuentra en investigación. Por lo poco común de la enfermedad y ser el primer caso en edad pediátrica en Cuba, se decidió su publicación.
Jadassohn-Lewandowsky syndrome or congenital pachyonychia type 1 belongs to the rare diseases' group. Worldwide, less than a thousand cases have been described to date and the one that is now published constitutes the first pediatric age report in Cuba. A seven-years-old male patient admitted to the Pediatric Clinic Service at the Holguín Provincial Pediatric Hospital with a history of yellow and hypertrophic nails since he was nine months old. The physical examination confirmed the presence of hypertrophic nail dystrophy in all 20 nails, keratosis follicularis on the elbows, hands and lower limbs, focal plantar keratoderma and oral leukokeratosis. An autosomal dominant inheritance pattern was identified. Based on the phenotypic characteristics and family history, the case presented was classified as congenital pachyonychia type 1, for which there is still no cure and gene therapy is under investigation. Due to the rareness of the disease and being the first pediatric age case in Cuba, its publication was decided.
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The gold standard for the diagnosis of oral cancer is the microscopic analysis of specimens removed preferentially through incisional biopsies of oral mucosa with a clinically detected suspicious lesion. This dataset contains captured histopathological images of oral squamous cell carcinoma and leukoplakia. A total of 237 images were captured, 89 leukoplakia with dysplasia images, 57 leukoplakia without dysplasia images and 91 carcinoma images. The images were captured with an optical light microscope, using 10x and 40x objectives, attached to a microscope camera and visualized through a software. The images were saved in PNG format at 2048 × 1536 size pixels and they refer to hematoxylin-eosin stained histopathologic slides from biopsies performed between 2010 and 2021 in patients managed at the Oral Diagnosis project (NDB) of the Federal University of Espírito Santo (UFES). Oral leukoplakias were represented by samples with and without epithelial dysplasia. Since the diagnosis considers socio-demographic data (gender, age and skin color) as well as clinical data (tobacco use, alcohol consumption, sun exposure, fundamental lesion, type of biopsy, lesion color, lesion surface and lesion diagnosis), this information was also collected. So, our aim by releasing this dataset NDB-UFES is to provide a new dataset to be used by researchers in Artificial Intelligence (machine and deep learning) to develop tools to assist clinicians and pathologists in the automated diagnosis of oral potentially malignant disorders and oral squamous cell carcinoma.