Eficacia clínica de la terapia fotodinámica por 5-ALA tópico en el manejo onco-preventivo de lesiones de leucoplasia oral. Una revisión sistemática / Clinical efficacy of topical 5-ALA photodynamic therapy in the onco-preventive management of oral leukoplakia lesions. A systematic review

Objetivo: La leucoplasia oral es el desorden maligno de la mucosa bucal más prevalente a nivel global y su manejo clínico sigue siendo un desafío. Se llevó a cabo una revisión sistemática para determinar la eficacia clínica de la terapia fotodinámica mediada por ácido 5-aminolevulínico tópico como una alternativa de quimio-prevención para las diferen- tes formas clínicas de la leucoplasia oral. Materiales y métodos: Empleando términos MeSH, se realizó una búsqueda exhaustiva en diferentes bases digi- tales de ensayos clínicos publicados en inglés en los últimos 30 años acerca del uso de la terapia fotodinámica mediada por ácido 5-aminolevulínico tópico como fotosensibilizador, y radiación láser de baja intensidad o luz LED como posibles fuentes de iluminación. Resultados: La revisión sistematizada que aplicó la guía PRISMA mostró una eficacia del 88,6% para este modo de fototerapia en el manejo de leucoplasias orales, con un 60,7% de respuesta completa y 27,9% de respuesta parcial. Además, el tamaño de efecto fue mayor para las formas clíni- cas homogéneas con cambios displásicos, independientemen- te del tipo de fuente de luz. La ausencia de respuesta fue del 11,4%, pero la evidencia empleada en este análisis fue mo- derada. Conclusión: La terapia fotodinámica mediada por áci- do 5-aminolevulínico tópico parece ser una alternativa útil en el manejo onco-preventivo de lesiones de leucoplasia oral. Sin embargo, es recomendable ejecutar ensayos clínicos controla- dos y aleatorizados con metodologías homogéneas que per- mitan generar un meta-análisis con un alto nivel de evidencia

Aim: Oral leukoplakia is globally the most prevalent ma- lignant disorder of the oral mucosa and its clinical manage- ment remains a challenge. A systematic review was carried out to determine the clinical efficacy of photodynamic therapy mediated by topical 5-aminolevulinic acid as an alternative for chemoprevention in the different clinical forms of oral leu- koplakia. Materials and methods: Using MeSH terms, an ex- haustive search was carried out in different digital databases of clinical trials published in English in the last 30 years on the use of photodynamic therapy mediated by topical 5-ami- nolevulinic acid as a photosensitizer, and low-intensity laser radiation or LED light as possible lighting sources. Results: The systematized review using PRISMA guide- lines showed an efficacy of 88.6% for this mode of photother- apy in the management of oral leukoplakias, based on 60.7% of complete response and 27.9% of partial response. In addi- tion, the effect size was larger in homogeneous clinical forms with dysplastic changes, regardless of the type of light source. There was an 11.4% of absence of response, but the evidence used in this analysis was moderate. Conclusion: Photodynamic therapy mediated by topical 5-aminolevulinic acid seems to be a useful alternative in the onco-preventive management of oral leukoplakia lesions. However, it is recommendable to perform controlled and ran- domized clinical trials with homogeneous methodologies that allow the generation of a meta-analysis with a high level of evidence (AU)

Variaciones celulares de la mucosa bucal en pacientes portadores de prótesis dental completa / Cellular variations of the oral mucous in patients with complete dental prosthesis i: en

Introducción: La prótesis dental completa genera una reacción tisular en el medio bucal, cuyo diagnóstico puede ser confirmado mediante el estudio citológico, que constituye una herramienta imprescindible para identificar cambios displásicos tempranos de la mucosa subprótesis. Objetivo: Identificar las posibles variaciones celulares de la mucosa bucal en pacientes portadores de prótesis completa. Métodos: Se realizó un estudio descriptivo y transversal en la Clínica Estomatológica Provincial Docente Mártires del Moncada de Santiago de Cuba, de junio de 2014 a enero de 2019, de 100 pacientes atendidos en la consulta de Prótesis Estomatológica, a los cuales se les realizó el raspado citológico de la mucosa del paladar y los rebordes para su posterior análisis microscópico según variables de interés. Para el procesamiento estadístico se empleó el porcentaje como medida de resumen y el estadígrafo de la Χ2, con un nivel de significación de 0,05. Resultados: En la serie predominaron las displasias leves (66,7 %), que resultaron más frecuentes en las edades de 20 a 39 años (12,5 %), en tanto, las moderadas y las graves figuraron principalmente en el grupo etario de 60 y más años (9,3 y 27,7 %, respectivamente). Todos los tipos de displasia primaron en los pacientes que habían portado la prótesis por más de 5 años y afectaron mayormente la queratina; de igual modo, entre las lesiones observadas, la estomatitis afectaba a un mayor porcentaje (31,2), sobre todo en el paladar (82,3 %), mientras que 8,3 % correspondió a la leucoplasia. Conclusión: Las pruebas citológicas son imprescindibles para la confirmación diagnóstica de cambios displásicos y posibilitan la prevención temprana del cáncer bucal.

Introduction: The complete dental prosthesis generates a tisular reaction in the oral cavity which diagnosis can be confirmed by means of citological study that constitutes an indispensable tool to identify early dysplastic changes of the subprosthesis mucous. Objective: To identify the oral possible cellular variations of the oral mucous in patients with complete prosthesis. Methods: A descriptive and cross sectional study was carried out in Mártires del Moncada Provincial Stomatological Clinic of Santiago de Cuba, from June, 2014 to January, 2019, with 100 patients, assisted in the Stomatological Prosthesis Department to whom the cytological scrapings of the palate and the edges were carried out for their later microscopic analysis according to variables of interest. For the statistical procedures, the percentage was used as summary measure and the Chi squared statistician, with a significance level of 0,05. Results: In the series the mild dysplasias prevailed (66,7%) that were more frequent in the 20 to 39 age group (12,5%), while the moderate and the serious dysplasias figured mainly in the age group of 60 and over (9,3 and 27,7%, respectively). All the dysplasia types prevailed in the patients that had carried the prosthesis for more than 5 years and they mostly affected the keratin; in a same way, among the observed lesions, the stomatitis affected a higher percentage (31,2), mainly in the palate (82,3%), while 8,3% corresponded to the leukoplakia. Conclusion: The cytological checkups are indispensable for the diagnostic confirmation of dysplasic changes and they allow to prevent early oral cancer.

Malignant transformation of oral leukoplakia to squamous cell carcinoma

Oral leukoplakia is a potentially malignant lesion found more in the middle-aged and elderly, with an estimated global prevalence of 2.60%. Most oral squamous cell carcinomas develop on the background of oral leukoplakia. The risk of malignant transformation increases with the clinical type of leukoplakia, affected sites, immunosuppressive states of affected patients, alcohol and tobacco consumption, human papilloma virus infection, and chewing betel leaf and areca nut. Regular monitoring of patients with oral leukoplakia is very important for early detection of any mucosal and dysplastic change. This will aid early intervention and improve patient's survival.

Análise do perfil microbiano de lesões orais potencialmente malignas / The microbial profile of potentially malignant oral disorders

As lesões orais potencialmente malignas são alterações que exibem maior risco de transformação maligna em comparação com a mucosa saudável. Apesar de sua relevância, a literatura ainda não definiu o papel da microbiota na etiologia e no processo de malignização dessas lesões. Assim, neste trabalho, realizamos um estudo do tipo caso controle de caráter longitudinal, prospectivo e quantitativo onde avaliamos as populações bacterianas do microbioma oral em pacientes com lesões orais potencialmente malignas. Para isso, utilizamos um questionário estruturado e coletamos swabs orais em pacientes portadores de leucoplasia, eritroplasia, líquen plano, lesão liquenóide oral e também controles saudáveis. Participaram do estudo 60 indivíduos, no período de coleta de 2018 à 2020,sendo 39 do grupo caso e 21 do grupo controle. A maioria dos pacientes era do sexo feminino (42/60; 70%) com média de idade de 57 anos, e mais da metade dos indivíduos eram não fumantes (35/60; 58,3%) e etilistas (36/60; 60%). Dentre os diagnósticos, observamos a maioria dos indivíduos com líquen plano oral/lesão liquenóide oral (13/39), seguidos de leucoplasia homogênea (10/39), eritroleucoplasia (8/39), leucoplasia verrucosa proliferativa (6/39) ou eritroplasia (2/39). A borda da língua foi o local mais comumente acometido, com a maioria apresentando múltiplos sítios (21/39). A displasia epitelial foi avaliada nas lesões, exceto líquen plano e lesões liquenóides, e 18 pacientes tiveram algum grau de displasia. Um total de 73 amostras tiveram a região V3-V4 do gene 16S rRNA amplificada e sequenciada, sendo 60 amostras referentes à primeira coleta e 13 ao segundo momento de coleta dos participantes do grupo caso, sendo que 3/13 desses indivíduos vieram a ter um diagnóstico de carcinoma espinocelular oral. Identificamos maior quantidade de genomas bacterianos por genomas humanos nas amostras do grupo caso, no entanto, a diversidade e composição bacteriana foram semelhantes entre casos e controles. No total, identificamos 9 filos, 15 classes, 24 ordens, 47 famílias e 67 gêneros bacterianos. O gênero mais abundante foi Streptococcus em ambos os grupos, com menor frequência nos casos. Encontramos ainda alta abundância dos gêneros Granulicatella e Blautia nos indivíduos com lesões orais e menor abundância de Methylobacterium, Lautropia e Oribacterium. Observamos também que a abundância de Granulicatella e Bergeyella foi maior nas lesões com displasia epitelial. A transformação maligna em carcinoma espinocelular oral ocorreu em 10/39 (25,6%) dos casos, onde a presença de displasia epitelial aparentou ser um fator de risco relevante. A diversidade bacteriana foi semelhante entre os indivíduos do grupo caso que sofreram ou não malignização, porém, a abundância dos gêneros Capnocytophaga, Finegoldia, Prevotella e Prevotella 2 foi maior nas amostras que sofreram malignização, mesmo antes do processo acontecer. Não encontramos diferenças na composição bacteriana entre os dois tempos de coleta, ao diagnóstico e após aproximadamente um ano, e também não observamos diferenças significativas na quantidade de DNA bacteriano e humano. Ao inferirmos as vias metabólicas derivadas das bactérias identificadas nas amostras, observamos também similaridade entre os grupos caso e controle, e apenas duas vias preditas apresentaram abundância com diferenças estatisticamente significativas entre ambos. Dessa maneira, nossos resultados sugerem que distúrbios orais potencialmente malignos podem estar associados a uma disbiose do microbioma oral, e que alguns gêneros bacterianos podem ser potenciais biomarcadores ou agentes importantes neste processo biológico.

Oral potentially malignant disorders have a higher risk of becoming cancer than healthy mucosal tissues. However, up until now, the literature did not define the role of the microbiota in the origin and development of malignancy in these lesions. Thus, here we conducted a longitudinal, prospective, and quantitative case-control study where we evaluated the bacterial composition of the oral microbiome in patients with potentially malignant lesions. Therefore, we used a structured questionnaire and performed oral swabs on patients with leukoplakia, erythroplakia, lichen planus, oral lichenoid lesion, and healthy controls. A total of 60 individuals, collected between 2018 to 2020, were enrolled in the study, of which 39 were cases and 21 were controls. The majority of patients were female (42/60; 70%) with a mean age of 57 years and over half of the individuals were non-smokers (35/60; 58.3%) and alcoholics (36/60; 60%). Among the diagnoses, there were oral lichen planus/oral lichenoid lesion (13/39), homogeneous leukoplakia (10/39), erythroleukoplakia (8/39), proliferative verrucous leukoplakia (6/39) and erythroplakia (2/39). The tongue edge was the most common location affected, with the majority having multiple sites (21/39). Epithelial dysplasia was assessed in the lesions, except for lichen planus and lichenoid lesions, and 18 patients had some degree of dysplasia. A total of 73 samples had the V3-V4 region of the 16S rRNA gene amplified and sequenced, in which 60 samples were collected at diagnosis (first collection point) and 13 samples were collected after approximately a year (second moment of collection). At least 03/13 of these patients were later diagnosed with oral squamous cell carcinoma. We identified a higher amount of bacterial per human genomes in the samples of the case group, however, the bacterial diversity and composition were similar between cases and controls. We identified 9 phyla, 15 classes, 24 orders, 47 families, and 67 bacterial genera. The most abundant genus was Streptococcus in both groups, with lower relative frequency in the individuals with potentially malignant lesions. We found a higher abundance of the genera Granulicatella and Blautia in the cases and lower abundance of Methylobacterium, Lautropia, and Oribacterium. We also observed that the abundance of Granulicatella and Bergeyella increased in the lesions with epithelial dysplasia. Malignant transformation into oral squamous cell carcinoma occurred in 10/39 (25.6%) of the cases patients, where the presence of epithelial dysplasia was a relevant risk factor. The bacterial diversity was similar between the individuals in the case group regardless if they malignized or not, however, the abundance of the genera Capnocytophaga, Finegoldia, Prevotella, and Prevotella 2 was higher in the samples that underwent malignization, even before this process took place. We did not find significant differences in the bacterial composition between the two collection points and we also did not observe significant differences in their amount of bacterial and human DNA. When inferring the metabolic pathways derived from the bacteria identified in the samples, we also observed similarity between the case and control groups, and only two predicted pathways showed abundance with statistically significant differences between them. Thus, our results suggest that potentially malignant oral disorders may be associated with a dysbiosis of the oral microbiome, and that some bacterial genera may be potential biomarkers or important agents in this biological process.

Nicotine promotes the development of oral leukoplakia via regulating peroxiredoxin 1 and its binding proteins

Tobacco can induce reactive oxygen species (ROS) production extensively in cells, which is a major risk factor for oral leukoplakia (OLK) development. Peroxiredoxin 1 (Prx1) is a key antioxidant protein, upregulated in a variety of malignant tumors. We previously found that nicotine, the main ingredient of tobacco, promotes oral carcinogenesis via regulating Prx1. The aim of the present study was to screen and identify the Prx1 interacting proteins and investigate the mechanisms of nicotine on the development of OLK. Through liquid chromatography-tandem mass spectrometry combined with bioinformatics analysis, the candidate Prx1 interacting proteins of cofilin-1 (CFL1), tropomyosin alpha-3 chain (TPM3), and serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform (PPP2R1A) were screened in human dysplastic oral keratinocyte cells treated with nicotine. CFL1, TPM3, and PPP2R1A were highly expressed in human OLK tissues. The expression of CFL1 increased and the expression of PPP2R1A decreased in OLK of smokers compared to that in OLK of non-smokers. Nicotine upregulated CFL1 and downregulated PPP2R1A in 4-nitro-quinoline-1-oxide (4NQO)-induced OLK tissues in mice in part dependent on Prx1. Furthermore, the in-situ interaction of CFL1, TPM3, and PPP2R1A with Prx1 were validated in human OLK tissues. Our results suggested that tobacco might promote the development of OLK via regulating Prx1 and its interacting proteins CFL1 and PPP2R1A.

Alteration in Serum Lipid Profile Pattern in Oral Squamous Cell Carcinoma and Potentially Malignant Disorders

ABSTRACT Objective: To evaluate and compare lipid profile level in oral submucous fibrosis (OSMF), oral leukoplakia (OL) and oral squamous cell carcinoma (OSCC) patients. Material and Methods: Thirty histopathologically diagnosed subjects each of OL, OSMF, OSCC were recruited along with 30 healthy controls. 5ml of venous blood is collected and estimated using standard diagnostic kits. Results: The mean of Total cholesterol level in controls was 219.03 mg%, in OSCC, OL and OSMF was 142.89 ± 10.21mg%, 155.44 ± 17.63 mg% and 180.60 ± 13.25 mg%, respectively. The mean low-density lipid level in controls was 137.24 mg and in OSCC, OL and OSMF groups were 109.28 ± 2.16 mg%, 126.63 ± 0.85 mg% and 119.15 ± 0.93 mg%, respectively. The mean of high-density lipid level in controls, OSCC, OL and OSMF was 42.87 ± 0.42 mg%, 36.50 ± 2.31 mg%, 21.13 ± 0.77 mg% and 28.37 ± 1.11mg%, respectively. The mean of very low density lipids level in controls, OSCC, OL and OSMF was 30.12 ± 1.51 mg%, 17.24 ± 0.80 mg%, 22.25 ± 0.93 mg% and 25.89 ± 0.43 mg%, respectively. The mean triglyceride level in controls, OSCC, OL and OSMF was 118.80 ± 9.47 mg%, 91.2 ± 3.03 mg%, 105.05 ± 2.96 mg% and 106.19 ± 3.09 mg%, respectively. Conclusion: Lipid profile levels could be early indicators of precancer and cancer.

Correlation Between Clinical and Histopathologic Diagnosis of Oral Potentially Malignant Disorder and Oral Squamous Cell Carcinoma

ABSTRACT Objective: To determine the frequency of oral potentially malignant disorders and Oral Squamous Cell Carcinoma (OSCC) and evaluate the consistency between their clinical and pathological features. Material and Methods: This retrospective study was conducted on records with a diagnosis of oral leukoplakia, oral erythroplakia, erythroleukoplakia, actinic cheilitis, lichen planus, and OSCC in the Pathology Department of Kerman dental school from September 1997 to September 2017. Data were analyzed in SPSS 21 at the significance level of ≤5%. Results: There were 378 cases of oral potentially malignant disorders and 70 cases of OSCC with a mean age of 46.82 ± 15.24 years. Buccal mucosa was the most frequent site, and lichen planus the most common lesion. Females were significantly older than males in leukoplakia and carcinoma in situ lesions. Clinical diagnosis and histopathology were consistent in 69.03% of cases. Conclusion: Clinical and histopathological diagnoses were consistent in 69.03% of records. The highest degree of clinical compliance with histopathology was observed in OSCC. Dentists should pay attention to oral potentially malignant disorders for early diagnosis to prevent their transformation to malignancy.

Randomized comparative study in the treatment of oral leucoplakia with laser and conventional surgery / Estudo comparativo randomizado no tratamento da leucoplasia oral com laser e cirurgia convencional

Objective: High-energy lasers are used as an alternative to surgical treatment of potentially malignant disorders in the oral cavity. The present article aims to make a prospective randomised comparative clinical assessment of the effect of laser surgery and conventional surgery in the treatment of oral leukoplakia (OL). Material and methods: In the study were included 89 patients with histologically confirmed oral leukoplakia lesions. Laser excision of the lesions using Er YAG laser was performed in 36 of the patients, while standard surgical excision was used in 53 of the cases. Following clinical assessment comparing the two treatment methods was conducted based on: pain, wound healing, infection and recurrence of the lesions. Results: A statistically significant difference between two groups according pain in the postoperative period was found. Patients treated with laser ablation experienced far less pain than those treated with surgical excision. The healing time was significantly faster in the group treated with Er YAG laser, and regarding the occurrence of postoperative infections, the results of the two methods did not differ significantly. Recurrence was observed earlier in the group treated with laser ablation, but the levels align over a longer period of time. Conclusion: Er YAG laser ablation is a contemporary method for the treatment of oral leukoplakia without dysplasia, providing similar success, compared to conventional surgical excision, with less postoperative discomfort for the patients. (AU)

Objetivo: Os lasers de alta potência são utilizados como alternativa ao tratamento cirúrgico de doenças potencialmente malignas da cavidade oral. O presente artigo tem como objetivo fazer uma avaliação clínica prospectiva e randomizada comparativa do efeito da cirurgia a laser e da cirurgia convencional no tratamento da leucoplasia oral (LO). Material e Métodos: No estudo foram incluídos 89 pacientes com lesões de leucoplasia oral confirmadas histologicamente. A excisão das lesões com laser Er YAG foi realizada em 36 dos pacientes, enquanto a excisão cirúrgica padrão foi utilizada em 53 dos casos. A avaliação clínica seguinte comparando os dois métodos de tratamento foi realizada com base em: dor, cicatrização da ferida, infecção e recorrência das lesões. Resultados: Foi encontrada diferença estatisticamente significante entre os dois grupos de acordo com a dor no pós-operatório. Os pacientes tratados com ablação a laser experimentaram muito menos dor do que aqueles tratados com excisão cirúrgica. O tempo de cicatrização foi significativamente mais rápido no grupo tratado com laser Er YAG e, em relação à ocorrência de infecções pós-operatórias, os resultados dos dois métodos não diferiram significativamente. A recorrência foi observada mais cedo no grupo tratado com ablação a laser, mas os níveis se alinham por um longo período de tempo. Conclusão: A ablação a laser Er YAG é um método contemporâneo para o tratamento da leucoplasia oral sem displasia, proporcionando sucesso semelhante ao da excisão cirúrgica convencional, com menor desconforto pós-operatório para os pacientes. (AU)

Cigarette smoke promotes oral leukoplakia via regulating glutamine metabolism and M2 polarization of macrophage / 国际口腔科学杂志·英文版

Oral immunosuppression caused by smoking creates a microenvironment to promote the occurrence and development of oral mucosa precancerous lesions. This study aimed to investigate the role of metabolism and macrophage polarization in cigarette-promoting oral leukoplakia. The effects of cigarette smoke extract (CSE) on macrophage polarization and metabolism were studied in vivo and in vitro. The polarity of macrophages was detected by flow cytometric analysis and qPCR. Liquid chromatography-mass spectrometry (LC-MS) was used to perform a metabolomic analysis of Raw cells stimulated with CSE. Immunofluorescence and flow cytometry were used to detect the polarity of macrophages in the condition of glutamine abundance and deficiency. Cell Counting Kit-8 (CCK-8), wound-healing assay, and Annexin V-FITC (fluorescein isothiocyanate)/PI (propidium iodide) double-staining flow cytometry were applied to detect the growth and transferability and apoptosis of Leuk-1 cells in the supernatant of Raw cells which were stimulated with CSE, glutamine abundance and deficiency. Hyperkeratosis and dysplasia of the epithelium were evident in smoking mice. M2 macrophages increased under CSE stimulation in vivo and in vitro. In total, 162 types of metabolites were detected in the CSE group. The metabolites of nicotine, glutamate, arachidic acid, and arginine changed significantly. The significant enrichment pathways were also selected, including nicotine addiction, glutamine and glutamate metabolism, and arginine biosynthesis. The results also showed that the supernatant of Raw cells stimulated by CSE could induce excessive proliferation of Leuk-1 and inhibit apoptosis. Glutamine abundance can facilitate this process. Cigarette smoke promotes oral leukoplakia via regulating glutamine metabolism and macrophage M2 polarization.

Transcriptome array screening and verification of oral leukoplakia carcinogenesis-related hypoxia-responsive gene and microRNA / 华西口腔医学杂志

OBJECTIVES@#To study the hypoxia response gene and microRNA (miRNA) expression profiles in the pathogenesis and progression of oral leukoplakia (OLK).@*METHODS@#Affymetrix GeneChip human transcriptome array 2.0 was used to detect the transcriptome of normal mucosa, low-risk OLK, high-risk OLK, and early squamous cell carcinoma (SCC). Gene ontology function analysis was used to screen genes and key miRNAs whose biological role is hypoxia response. Quantitative reverse transcription polymerase ch-ain reaction (qRT-PCR) was used to verify the expression of hypoxia response genes and miRNAs.@*RESULTS@#A total of 7 different genes of hypoxia response between normal mucosa and low-risk OLK, 10 genes between low-risk and high-risk OLK, and 21 genes between high-risk OLK and SCC were identified. The results of qRT-PCR showed that the expression of hypoxia-inducible factor 1α, chemokine cc-motif ligand 2, and matrix metalloproteinase 3 mRNA and miR-21 in normal mucosa, OLK, and SCC increased in a stepwise manner. The expression difference between OLK and SCC was statistically significant and consistent with the results of transcriptome array.@*CONCLUSIONS@#The hypoxia response gene and related miRNA play roles in the development and progression of OLK.

Expression of Ki-67, Cyclin D1, P53, and P16 in patients with oral leukoplakia and leukoplakia cancerization with spicy diet in Chengdu / 华西口腔医学杂志

OBJECTIVES@#To investigate the expression of Ki-67, Cyclin D1, P53, and P16 in patients with oral leukoplakia (OLK) and OLK cancerization who have aspicy diet in Chengdu.@*METHODS@#Thirtypatients with OLK andspicy diet and 15 patients with OLK without spicy diet in Chengdu were divided into three groups: hyperplastic OLK (OLK-), OLK with mild to moderate dysplasia (OLK+), and severe dysplastic  OLK or oral squamous cell carcinoma (OSCC) transforming from OLK (OLK++/OSCC). The expression of Ki-67, Cyclin D1, P53, and P16 were detected by immunohistochemistry and statistically analyzed.@*RESULTS@#The expression of Ki-67 and P53 in patients with or without spicy diet in the OLK+and OLK++/OSCC groups were stronger than that of the OLK- group (@*CONCLUSIONS@#Spicy diet did not have an influence on the expression of Ki-67, Cyclin D1, P53, and P16 in patients with OLK and OSCC. The expression of Ki-67, Cyclin D1, and P53 increased with the development of OLK, whereas P16 showed opposite expression trend.

La Relación entre la Salud Oral y el Consumo de Tabaco. Un Estudio de los Habitantes de la Rioja Alta / The Relationship Between Oral Health and Tobacco Consumption. A Study of the Inhabitants of La Rioja Alta

RESUMEN: Estudiar los efectos del consumo de tabaco (producto adictivo) en la salud de los pacientes sigue siendo una prioridad para la sociedad. Tras la lectura de "La Historia Medicinal de las cosas que se traen de nuestras Indias Occidentales" de Nicolás Monardes se realizó una lista de todos los beneficios que se le atribuían al tabaco. Uno de los pocos que no han sido refutados es el del consumo de tabaco para el dolor de muelas. Por ello el objetivo del estudio es relacionar el consumo de tabaco con la salud bucodental (caries) para replicar la afirmación de Monardes. Estudio piloto con pacientes que acuden al dentista en el área de La Rioja Alta (España). Se pidió permiso a los individuos que acudían para tratar sus datos personales en el estudio. Se utilizó estadística descriptiva. Ochenta y tres pacientes cedieron sus datos para la realización del estudio, siendo la mayoría mujeres (59.13%). La mayoría no son consumidores de tabaco, los consumidores son en su totalidad fumadores diarios. El número medio de caries de la población es de 2.74, siendo el de los fumadores 3.90 y el de los no fumadores 2.10. El número tan bajo de la muestra no permite realizar un estudio de significatividad. Pero, un primer resultado evidencia que los fumadores tienen una peor salud bucodental, lo que los lleva a tener más caries. Esta diferencia no es tan acuciada si se realiza el estudio entre otras variables (sexo, localidad o edad).

ABSTRACT: Studying the effects of tobacco use (addictive product) on the health of patients continues to be a priority for society. After reading " La Historia Medicinal de las cosas que se traen de nuestras Indias Occidentales " by Nicolás Monardes, a list of all the benefits attributed to tobacco was made. One of the few that has not been refuted is the use of tobacco for toothache. Therefore, the objective of the study is to relate the consumption of snuff with oral health (caries) to replicate the claim of Monardes. A pilot study with patients who visit the dentist in La Rioja Alta (Spain) was carried out. Permission was sought from the individuals who came to discuss their personal data in the study. Descriptive statistics was used. Eighty-three patients gave their data for the study, with the majority being women (59.13%). The majority are not tobacco consumers; tobacco users are in their entirety daily smokers. The average number of caries of the population is 2.74, being that of smokers 3.90 and that of non-smokers 2.10. The low number of the sample does not allow a study of significance. However, initial results show that smokers have worse oral health, which leads them to have more cavities. This difference is not critical if the study includes other variables (sex, location or age).

Prevalencia de lesiones bucales en tejido blando encontradas en la Clínica de Estomatología de la Facultad de Odontología de la Universidad de los Andes: periodo 2015-2018 / Prevalence of oral lesions in soft tissue found in the Clinic of Stomatology of the Faculty of Dentistry of the University of los Andes: 2015-2018 period

Introducción: La epidemiología sobre alteraciones en tejidos blandos bucales es limitada cuando se compara con caries, enfermedades periodontales y maloclusiones, por lo que su estudio representa un paso adelante en la odontología más allá de los dientes. Objetivo: Describir la prevalencia de las lesiones bucales en tejido blando encontradas en la Clínica de Estomatología de la Facultad de Odontología de la ULA, del 2015 al 2018, con la finalidad de proporcionar una fuente de datos actualizada, que oriente a una mejor prevención y oportuno diagnóstico. Material y métodos: Se realizó una investigación descriptiva, documental, retrospectiva y multivariable. Resultados: De 1,000 fichas clínicas estudiadas, las patologías más frecuentes fueron: lengua saburral (50.6%), queilitis (33.4%), traumatismo de la mucosa de los carrillos (27.6%), várices linguales (18.3%), anquiloglosia (13.7%) y agrandamiento de rugas palatinas (11.7%). La zona con mayor alteración fue la lengua (92.1%), mientras que el paladar fue la menos afectada (29%). De los hábitos predisponentes a la formación de lesiones, el mordisqueo de mucosa fue el más común (16.5%). En cuanto a los factores locales asociados, una higiene oral regular/ deficiente resultó el principal (53.8%). Conclusión: La educación del paciente sigue siendo considerada la clave para disminuir la aparición de patologías y su evolución a entidades más graves (AU)

Introduction: Epidemiological studies on soft tissue alterations in the mouth are limited when compared with caries, periodontal diseases and malocclusions, so their study represents a step forward in dentistry beyond the teeth. Objective: To describe the prevalence of soft tissue oral lesions found in the Stomatology Clinic of the ULA School of Dentistry, from 2015 to 2018, in order to provide an up-to-date data source, to guide better prevention and timely diagnosis. Material and methods: A descriptive and documentary, retrospective and multivariable research was carried out. The statistical package IBM SPSS Statistics v 23 was applied for the analysis. Results: 1,000 clinical records studied, the most frequent pathologies were: saburral tongue (50.6%), cheilitis (33.4%), traumatism of the cheek mucosa (27.6%), lingual varices (18.3%), ankyloglossia (13.7%) and enlargement of palatal rugas (11.7%). The tongue was the most affected (92.1%), while the palate was the least affected (29%). Of the predisposing habits to the formation of lesions, mucosal nipping was the most common (16.5%). Regarding the associated local factors, a regular / deficient oral hygiene was the main one (53.8%). Conclusion: Patient education is still considered the key to diminish not only the appearance of pathologies but their evolution to more serious entities (AU)

Caracterización clínica y epidemiológica de pacientes con leucoplasia bucal / Clinical epidemiological characterization of patients with oral leukoplakia

Introducción: La leucoplasia bucal se presenta clínicamente de múltiples formas. Actualmente se considera que puede ser homogénea o no homogénea. Objetivo: Caracterizar pacientes con leucoplasia bucal según variables seleccionadas. Métodos: Se realizó un estudio descriptivo y transversal de 30 pacientes con leucoplasia, atendidos en la consulta del Programa de Detección del Cáncer Bucal, pertenecientes al área de salud del Policlínico Universitario Carlos Juan Finlay de Songo La Maya, provincia de Santiago de Cuba, durante el 2016. Se analizaron las siguientes variables: edad, sexo, color de la piel, factores de riesgo, formas clínicas de presentación de la leucoplasia, localización, número de lesiones, tiempo de consumo del tabaco y transformación maligna. Resultados: Predominaron el grupo etario de 45-64 años, el sexo masculino y los mestizos. La localización anatómica más afectada fue el reborde alveolar residual. La mayoría de los afectados presentó una sola lesión con forma clínica homogénea, y ninguna transformación maligna después de su intervención. El tabaquismo fue el factor de riesgo de mayor prevalencia. Conclusiones: La detección temprana de las lesiones del complejo bucal depende de que el paciente sea examinado a tiempo. Se debe realizar un diagnóstico certero para lograr una reducción significativa de la morbilidad y la mortalidad e incrementar la curación y la supervivencia.

Introduction: The oral leukoplakia is clinically presented in multiple forms. At the moment it is considered that can be homogeneous or non homogeneous. Objective: To characterize patients with oral leukoplakia according to selected variables. Methods: A descriptive and cross-sectional study of 30 patients with leukoplakia was carried out, they were assisted in the Program of Detection of Oral Cancer service, belonging to the health area of Carlos Juan Finlay University Polyclinic in Songo La Maya, Santiago de Cuba, during 2016. The following variables were analyzed: age, sex, skin color, risk factors, clinical forms presentation of leukoplakia, localization, number of lesions, time of nicotine addiction and malignant transformation. Results: The 45-64 age group, male sex and persons of mixed race prevailed. The most affected anatomical localization was the residual alveolar edge. Most of those affected presented a single lesion with homogeneous clinical form, and any malignant transformation after their intervention. Nicotine addiction was the most prevalent risk factor. Conclusions: The early detection of the oral complex lesions depends on the patient's examination on time. An accurate diagnosis should be carried out to achieve a significant reduction of the morbidity and mortality and to increase cure and survival.

Expression profile of salivary micro RNA-21 and 31 in oral potentially malignant disorders

Abstract Oral potentially malignant disorders (OPMD) possess significant chances of malignancy conversion. In order to develop an early diagnostic tool, the present study evaluated the expression of miRNA-21 and 31 as salivary markers. The case-control study was carried out in 36 healthy participants as controls and in 36 patients who were newly diagnosed as OPMD having four different lesions including leucoplakia, oral sub mucous fibrosis (OSMF)궱, oral lichen planus, and (OSMF)궱 with leucoplakia. The samples were also classified as non-dysplastic, or with mild, moderate, and severe dysplasia according to their histopathological reports. The salivary miRNA-21 and 31 expressions were studied using real-time PCR. The statistical analysis was carried out using SPSS version 22. Salivary miRNA-21 (p-value = 0.02) and 31 (p-value = 0.01) were significantly upregulated in severe dysplasia compared with control. Among the different lesions, leucoplakia had significant upregulation of miRNA-21 and 31. miRNA-21 can be used as a diagnostic marker with specificity of 66% and sensitivity of 69%. The area under the ROC curve was 0.820 for miRNA-21 and 0.5 for miRNA-31, which proved that miRNA-21 is a better diagnostic marker than miRNA-31 for OPMD.

Protocolo de follow-up en leucoplasia proliferativa multifocal para evitar progresión maligna. Presentación de un caso clínico / Protocolo de acompanhamento em leucoplasia proliferativa multifocal para evitar progressão malignos. Apresentação de um caso clínico / Follow up protocol in proliferative multifocal leukoplakia to avoid malignant transformation. A case report

Resumen: La leucoplasia proliferativa multifocal (LPM) es considerada uno de los desórdenes potencialmente malignos (DPM) con mayor tasa de transformación carcinomatosa. La terapéutica es sumamente dificultosa ya que en la mayoría de los casos las lesiones son refractarias. El objetivo de este trabajo es presentar un caso de LPM y su evolución, destacando la importancia del seguimiento clínico mediante protocolos de follow up. Se presentó a la consulta una paciente de 75 años con múltiples lesiones queratóticas y verrugosas en toda la mucosa bucal y con un patrón de crecimiento proliferativo. Las biopsias y el contexto clínico permitieron encuadrarlo dentro del diagnóstico de LPM. La paciente adhirió a un protocolo estricto y hasta el momento se presenta libre de lesiones carcinomatosas. Este trabajo resalta el cuidadoso acompañamiento de los pacientes con este diagnóstico a fin de detectar precozmente carcinomas incipientes pudiendo mejorar el pronóstico de esta entidad.

Resumo: A leucoplasia proliferativa multifocal (LPM) é considerada um dos distúrbios orais potencialmente malignos (DOPM) com a maior taxa de transformação maligna. A terapêutica é extremamente difícil, pois na maioria dos casos as lesões são refratárias. O objetivo deste estudo é relatar um caso de LPM e sua evolução, destacando a importância do monitoramento clínico por meio de protocolos exaustivos de acompanhamento. Uma mulher de 75 anos com múltiplas lesões queratóticas e verrugas por toda a mucosa oral e com um padrão de crescimento proliferativo foi apresentada à consulta. As biópsias e o contexto clínico permitiram ajustá-lo ao diagnóstico de LPM. O paciente aderiu a um protocolo rigoroso e, até o momento, está livre de lesões carcinomatosas. Este trabalho destaca o acompanhamento cuidadoso dos pacientes com esse diagnóstico, a fim alcançar a detecção precoce do carcinoma epidermoide oral e, consequentemente, melhorar o prognóstico.

Abstract: Proliferative multifocal leukoplakia (PML) is considered one of the oral potentially malignant disorders (OPMD) with the highest malignant transformation rate. Therapeutics is extremely difficult since, in most cases, the lesions are refractory. This study aims to report a case of PML and its evolution, highlighting the importance of clinical monitoring through comprehensive follow-up protocols. A 75-year-old female with multiple keratotic and verrucous lesions with a proliferative growth pattern throughout the oral mucosa. The biopsies and the clinical context allowed clinicians to diagnose it as PML. The patient adhered to a strict protocol and so far has no carcinomatous lesions. This report highlights the careful monitoring of patients with PML to achieve early detection of oral squamous cell carcinoma and, consequently, improve prognosis.

DEC1: a potential biomarker of malignant transformation in oral leukoplakia

Abstract The purpose of this study was to analyze the differential expression of DEC1 in oral normal mucosa (NM), oral leukoplakia (OLK) and oral squamous cell carcinoma (OSCC). Surgically excised specimens from patients with OLK (n = 47), OSCC (n = 30) and oral normal mucosa (n=11) were immunostained for DEC1. The expression of DEC1 protein was evaluated, and its association with the clinicopathological features was analyzed. The expression of DEC1 in NM, OLK and OSCC tissues increased in turn, and significant differences were observed among the groups (P < 0.0001). In terms of the association between DEC1 expression and epithelial dysplasia, DEC1 expression was lower in hyperkeratosis without dysplasia (H-OLK) than in OLK with moderate to severe dysplasia (S-OLK), and these differences were significant (p < 0.05). The expression of DEC1 in OSCC with OLK was significantly higher than that in OSCC without OLK (p < 0.01). Therefore, DEC1 could be a potential biomarker of malignant transformation in the carcinogenesis of OSCC, which may provide a new research direction for the transformation of oral potentially malignant disorders (OPMDs) into OSCC.

CD4+, CD8+ and FOXP3+ lymphocytes infiltrating oral leukoplakia: an immunohistochemical analysis / Linfócitos CD4+, CD8+ e FOXP3+ que se infiltram na leucoplasia oral: uma análise imunohistoquimica

Objetivo: Avaliar a infiltraçãdo dos linfócitos CD4+ , CD8 + e FOXP3+ e sua correlação com caracteristicas sociodemográfica, clinicopatologicas e estilo de vida de pacientes com leucoplasias bucais. Pacientes e métodos: Oitenta pacientes com diagnóstico de leucoplasia bucal foram incluidos no estudo. Análises retrospectivas foram realizadas para verificar as características sociodemográficos, clinicopatológicos e estilo de vida dos pacientes. O infiltrado linfocitário foi caracterizado por imunoistoquímica com antígenos contra de CD4+ , CD8 + e FOXP3+ . Resultados: Dos 80 pacientes incluidos neste estudo, (60%) eram homens e a idade variou de 25 a 82 anos com idade média de 58,6 anos.Trinta e oito (47.5%) eram idosos, Trinta e dois (40%) eram adultos de meia idade e apenas dez (10%) adultos jovens. Sessenta e um dos pacientes eram fumantes (76.2%) e quarenta e seis eram etilistas (57.5%). Vinte e sete (35.5%) das lesões apresentaram algum grau de displasia epitelial. O grau de displasia epitelial apresentou correlação positiva com a intensidade do consumo do alcool (p=0.008). Houve correlação positiva entre os linfócitos CD4+ e CD8+ (p=0.005). Conclusão: O infiltrado linfocitário não foi relacionado com nenhuma característica clinicopatológica das lecoplasias bucais. Entretanto, o grau de displasia está relacionado ao estilo de vida dos pacientes(AU)

Objective: To evaluate the infiltration of CD4+ , CD8+ and FOXP3+ lymphocytes and their correlation with sociodemographic, clinicopathological and lifestyle characteristics of patients with oral leukoplakia. Patients and methods: Eighty patients diagnosed with oral leukoplakia were included in the study. Retrospective analyses were performed in order to verify the sociodemographic, clinicopathologic and lifestyle characteristics. The lymphocytic infiltrate characterization was performed by immunohistochemistry with antibodies against CD4+, CD8+, and FOXP3+ markers. Results: Of 80 patients included in the study, 60% were men, and their age ranged from 25 to 82 years, with a mean of 58.6. Thirty-eight patients (47.5%) were elderly, Thirty-two (40%) middle-aged, and only ten (10%) young adults. Sixty-one of the patients were smokers (76.2%) and forty-six were alcoholics (57.5%). Twenty-seven (35.5%) of the lesions presented some degree of dysplasia. The degree of epithelial dysplasia was correlated with the intensity of alcohol consumption (p=0.008). A positive correlation was found between CD4+ and CD8+ lymphocytes (p=0.005). Conclusion: The lymphocytic infiltrate of oral leukoplakia was not correlated with any clinicopathologic characteristic. However, the degree of epithelial dysplasia was correlated with the lifestyle of the patients(AU)

BMI-1 expression increases in oral leukoplakias and correlates with cell proliferation

Abstract Oral leukoplakia (OL) is a white lesion of an indeterminate risk not related to any excluded (other) known diseases or disorders that carry no increased risk for cancer. Many biological markers have been used in an attempt to predict malignant transformation; however, no reliable markers have been established so far. Objective To evaluate cell proliferation and immortalization in OL, comparing non-dysplastic (Non-dys OL) and dysplastic OL (Dys OL). Methodology This is a cross-sectional observational study. Paraffin-embedded tissue blocks of 28 specimens of Non-dys OL, 33 of Dys OL, 9 of normal oral mucosa (NOM), 17 of inflammatory hyperplasia (IH), and 19 of oral squamous cell carcinomas (OSCC) were stained for Ki-67 and BMI-1 using immunohistochemistry. Results A gradual increase in BMI-1 and K-i67 expression was found in oral carcinogenesis. The immunolabeling for those markers was higher in OSCC when compared with the other groups (Kruskal-Wallis, p<0.05). Ki-67 expression percentage was higher in OL and in IH when compared with NOM (Kruskal-Wallis/Dunn, p<0.05). Increased expression of BMI-1 was also observed in OL when compared with NOM (Kruskal-Wallis/Dunn, p<0.05). No differences were observed in expression of both markers when non-dysplastic and dysplastic leukoplakias were compared. A significant positive correlation between Ki-67 and BMI-1 was found (Spearman correlation coefficient, R=0.26, p=0.01). High-grade epithelial dysplasia was associated with malignant transformation (Chi-squared, p=0.03). Conclusions These findings indicate that BMI-1 expression increases in early oral carcinogenesis and is possibly associated with the occurrence of dysplastic changes. Furthermore, our findings indicate that both Ki-67 and BMI-1 are directly correlated and play a role in initiation and progression of OSCC.