A comparative study of the expression of cyclin D1, COX-2, and KI-67 in odontogenic keratocyst vs. ameloblastoma vs. orthokeratinized odontogenic cyst.

BACKGROUND: Odontogenic keratocysts (OKCs) and orthokeratinized odontogenic Cysts (OOCs) are distinct clinicopathological entities. OKC appears to behave in a way more similar to that of a neoplasm, such as ameloblastoma (AB). The aim of this study is to compare the influence of Ki-67, Cyclin D1 and COX-2 in the diagnosis and pathogenesis of OKC, OOC and AB. MATERIALS AND METHODS: A cross-sectional observational study of 41 samples was organized into 3 groups: (1) OKC n=22; (2) AB n=13 and (3) OOC n=6. Paraffin blocks were sectioned and stained with hematoxylin and eosin (H&E). Immunohistochemical study using Bond Polymer Refine Red Detection Kit, Leica, Wetzlar, Germany, was performed for the following antibodies: Ki-67, Cyclin D1 and COX-2. Double blind immunostaining was quantified subjectively. Staining: nuclear or cytoplasmic; nuclear (Ki-67 and Cyclin D1>5% positive) and cytoplasmic (COX-2; 1; 1-30 cytoplasm: 2; 31-60 cytoplasm; 3; 61-100 cytoplasm). Considering positive stained 61-100 cytoplasms. RESULTS: The expression of Ki-67 was higher in the OKC group than in the AB group (p<0.05). Cyclin D1 showed a higher expression in OKC vs. OOC and OKC vs. AB (p<0.05). Finally, expression of COX-2 was higher in OKC vs AB (p<0.05). CONCLUSIONS: COX-2, Ki-67 and Cyclin D1 show statistically significant differences between the groups, suggesting that they could be useful tools in the differential diagnosis between OKCs and OOC and a predictive indicator for their biologic behaviour. The higher expressions of these 3 markers of OKC vs AB highlight once more the aggressive behaviour of this now re-considered cystic lesion. These markers could prove useful in the choice of more aggressive surgical treatment in OKCs as their behaviour appears to be similar to that of a neoplasm.

A comparative study of the expression of cyclin D1, COX-2, and KI-67 in odontogenic keratocyst vs. ameloblastoma vs. orthokeratinized odontogenic cyst

Background: Odontogenic keratocysts (OKCs) and orthokeratinized odontogenic Cysts (OOCs) are distinct clinicopathological entities. OKC appears to behave in a way more similar to that of a neoplasm, such as ameloblastoma (AB). The aim of this study is to compare the influence of Ki-67, Cyclin D1 and COX-2 in the diagnosis and pathogenesis of OKC, OOC and AB. Materials and methods: A cross-sectional observational study of 41 samples was organized into 3 groups: (1) OKC n=22; (2) AB n=13 and (3) OOC n=6. Paraffin blocks were sectioned and stained with hematoxylin and eosin (H&E). Immunohistochemical study using Bond Polymer Refine Red Detection Kit, Leica, Wetzlar, Germany, was performed for the following antibodies: Ki-67, Cyclin D1 and COX-2. Double blind immunostaining was quantified subjectively. Staining: nuclear or cytoplasmic; nuclear (Ki-67 and Cyclin D1>5% positive) and cytoplasmic (COX-2; 1; 1–30 cytoplasm: 2; 31–60 cytoplasm; 3; 61–100 cytoplasm). Considering positive stained 61-100 cytoplasms. Results: The expression of Ki-67 was higher in the OKC group than in the AB group (p<0.05). Cyclin D1 showed a higher expression in OKC vs. OOC and OKC vs. AB (p<0.05). Finally, expression of COX-2 was higher in OKC vs AB (p<0.05). Conclusions: COX-2, Ki-67 and Cyclin D1 show statistically significant differences between the groups, suggesting that they could be useful tools in the differential diagnosis between OKCs and OOC and a predictive indicator for their biologic behaviour. The higher expressions of these 3 markers of OKC vs AB highlight once more the aggressive behaviour of this now re-considered cystic lesion. These markers could prove useful in the choice of more aggressive surgical treatment in OKCs as their behaviour appears to be similar to that of a neoplasm.(AU)

Antecedentes: Los queratoquistes odontogénicos (QQO) y los quistes odontogénicos ortoqueratinizantes (QOO) son entidades clínico-patológicas diferentes y el QQO parece estar más próximo al comportamiento de una neoplasia, como el ameloblastoma (AB). El objetivo de este estudio es comparar la influencia de Ki-67, ciclina D1, COX-2, en el diagnóstico y patogenia de QQO, QOO y AB. Materiales y métodos: Se ha diseñado un estudio observacional transversal con 41 muestras, en 3 grupos de estudio: (1) QQO: n=22, (2) AB n=13, y (3) QOO n=6. Se han seccionado bloques de parafina y teñido con hematoxilina y eosina y sometidas a una incubación con anticuerpos monoclonales (Kit Bond Polymer Refine Detection, Leica, Wezlar, Alemania) para la realización de un estudio inmunohistoquímico. Se ha cuantificado la inmunotinción, (nuclear o citoplasmática); nuclear (Ki-67 y ciclina D1; >5% positiva) y citoplasmática (COX-2; 1; 1-30 citoplasmas; 2; 31-60 citoplasmas; 3; 61-100 citoplasmas). Considerando positivo tinción a partir de 61-100 citoplasmas. Resultados: La expresión de Ki-67 ha sido mayor en el grupo del QQO con respecto a la de AB (p<0,05). Respecto a ciclina D1, mostró una expresión mayor en QQO vs. QOO (p<0,05); En el caso del marcador COX-2, la expresión ha sido mayor en QQO vs. AB (p<0,05). Conclusiones: La mayor expresión de estos 3 marcadores en QQO vs. AB resaltan una vez más el comportamiento agresivo de esta lesión ahora reconsiderada como «quística». Estos marcadores pueden ayudar a decidir tratamientos quirúrgicos más agresivos en las lesiones de QQO ya que parece comportarse como una «neoplasia».(AU)

TMJ arthroscopy with hyaluronic acid: A 12-month randomized clinical trial.

OBJECTIVES: To determine the effects of hyaluronic acid (HA) as an adjunct to temporomandibular joint (TMJ) arthroscopy, relative to standard TMJ arthroscopy, in Wilkes stage-III and stage-IV patients. METHODS: A randomized clinical trial design was utilized (ClinicalTrials.gov NCT04110587). 51 patients were allocated to a TMJ arthroscopy (n = 25) or a TMJ arthroscopy plus HA (n = 26) group. Visual analog scale joint pain scores, maximum mouth opening (MMO), and muscle pain were measured at baseline, and at 3, 6, 9, and 12 months. Disk position on magnetic resonance imaging was evaluated at baseline and 12 months. Oral health-related quality of life (OHRQoL) was assessed at baseline, and at 6 and 12 months. RESULTS: No group differences were observed in clinical or radiographic measurements (p ≥ .05). The results do not indicate any benefit of HA as an adjuvant therapy to arthroscopy during follow-up months 3-12. TMJ arthroscopy improved OHRQoL at 6 and 12 months (Oral Health Impact Profile-14 questionnaire scores of -14.59 and -14.27, 95% confidence intervals = -17.55 to -11.63 and -17.27 to -11.27) respectively, as well as pain and MMO, at all follow-up time points (p < .001). CONCLUSIONS: A beneficial effect of HA injection during TMJ arthroscopy after the 3-month follow-up was not observed.

Oral pulse granuloma and oral pulse granuloma associated with odontogenic keratocyst: two clinical cases and a review of the literature / Granuloma oral pulse y granuloma oral pulse asociado a un queratoquiste odontogénico: 2 casos clínicos y revisión de la literatura

Two cases of oral pulse granuloma (OPG) or vegetable granuloma (VG) are presented, one of which was concomitant with an odontogenic keratocyst (OKC), which is an unusual finding. OKC is characterized by the presence of hyaline rings which include vessels, giant cells, other inflammatory cells and collagen fibres. There are two hypotheses as to its histogenesis: firstly, as a reaction to vegetable matter, such as legumes (thus the nomenclature "pulse" or edible seed) and secondly as a degenerative change in the vessel walls as a result of localized vasculitis. Due to the deceptive appearance of OPG, diagnosis can be challenging

En este artículo breve se presentan 2 casos de granuloma oral pulse (GOP) o granuloma vegetal, uno de ellos asociado a un queratoquiste odontogénico. Esta entidad está caracterizada por la presencia de estructuras hialinas en anillo que incluyen vasos, células gigantes, otras células inflamatorias y haces de fibras de colágeno. Sobre su origen todavía se barajan 2 hipótesis: una en la que se sospecha que se producen como reacción a estructuras vegetales como legumbres (de donde toma el nombre de «pulse» o semilla comestible de una leguminosa), y otra en la que se trataría de un cambio degenerativo de las paredes vasculares, resultado de una vasculitis localizada. Debido a la apariencia engañosa del GOP es fácil que a los patólogos les suponga un esfuerzo su diagnóstico. Se describe a continuación un hallazgo inusual de un GOP relacionado con un queratoquiste odontogénico

Oral pulse granuloma and oral pulse granuloma associated with odontogenic keratocyst: Two clinical cases and a review of the literature.

Two cases of oral pulse granuloma (OPG) or vegetable granuloma (VG) are presented, one of which was concomitant with an odontogenic keratocyst (OKC), which is an unusual finding. OKC is characterized by the presence of hyaline rings which include vessels, giant cells, other inflammatory cells and collagen fibres. There are two hypotheses as to its histogenesis: firstly, as a reaction to vegetable matter, such as legumes (thus the nomenclature "pulse" or edible seed) and secondly as a degenerative change in the vessel walls as a result of localized vasculitis. Due to the deceptive appearance of OPG, diagnosis can be challenging.

Retrospective study of 149 cases of salivary gland carcinoma in a Spanish hospital population

BACKGROUND: The clinical and histological characteristics of salivary gland tumors vary widely, complicating their diagnosis and management, and major differences have been recorded in the distribution of histopathological diagnoses among different countries. MATERIAL AND METHODS: This retrospective study reviewed the demographic (age, sex) and clinicopathological (pathology diagnosis and localization) characteristics of cases diagnosed with primary SGC between June 1992 and May 2014 in the Pathology Department of the 12 de Octubre Hospital of Madrid. Diagnoses were recorded according to the 2005 WHO classification. RESULTS: The study included 149 SCG patients, aged between 11 and 94 yrs., with mean age at onset of 55.56 yrs and peak incidence in the eighth decade of life. The male: female ratio was 1.01. The parotid gland was the most frequently involved (75.2%). The most frequent carcinoma was mucoepidermoid carcinoma (24.2%), followed by acinic cell carcinoma (15.4%). CONCLUSIONS: The demographic and histopathological characteristics of patients with salivary gland carcinomas in Spain, reported here for the first time, are broadly similar to those found in other countries

Differences in the expression of five senescence markers in oral cancer, oral leukoplakia and control samples in humans.

Oncogene-induced senescence (OIS) may be a response to oncogenic activation, acting as a natural barrier against carcinogenesis at a premalignant stage. Thus, numerous cells in premalignant lesions enter senescence, but none or few in malignant tumours. This event could be due to the loss of senescence pathway effectors, including p16 (INK4a)-pRb or ARF-p53. The aim of this study was to characterize and compare the expression of certain senescent markers between oral precancer and cancer tissue samples. The expression of cyclin D1, Rb, maspin, p53 and mouse double minute 2 (MDM2) was analyzed in 20 paraffin-embedded tissue samples of normal oral mucosa (NOM), 14 samples of oral leukoplakia without dysplasia (OLD-), 11 samples of leukoplakia with dysplasia (OLD+) and 15 samples of oral squamous cell carcinoma (OSCC) by immunohistochemistry in tissue arrays. The expression of p16-pRb pathway markers, cyclin D1, maspin and Rb, was more frequent in OLD+ samples than in OSCC samples, although a statistical significance was only observed for maspin (P=0.036). Cyclin D1 expression was also significantly more frequent in OLD- samples vs. NOM samples. For the ARF-p53 pathway, the expression of p53 and MDM2 was significantly more frequent in the OLD- samples compared to in the NOM ones. These findings may indicate a role for cellular senescence in oral carcinogenesis, considering maspin as a reliable senescence marker and prognostic factor in oral premalignant lesions.

Peri-implant bone mechanobiology. Review of the literature

The mechanical load applied during bone regeneration in implant treatments influences the early formation ofperi-implant bone tissue through the activation of different pathways. The aim of this review was to determine thecurrently available scientific evidence in this field.Material and Mectronic search in medical databases (Medline, Pubmed and Cochrane Lierimentalstudies in animal models published from 2003 to 2009.Results: There is scientific evidence that the immediate application of an axial load in implantology stimulatesbone formation, as measured by various histomorphometric parameters. Different physiological mechanisms (e.g.,production of nitric oxide, prostaglandin E2) participate in this effect, although their action has not been fullyelucidated.Conclusion: The precise role of mechanical loading in the osseointegration process remains unknown. Furtherstudies are required to demonstrate the biological mechanisms involved and the load range producing the mosteffective response and to develop devices for obtaining predictable clinical outcomes (AU)

Host defence mechanisms against bacterial aggression in periodontal disease: Basic mechanisms

Periodontal diseases are complex bacteria-induced infections characterised by an inflammatory host response toplaque microbiota and their by-products. Most of these microorganisms have virulence factors capable of causingmassive tissue destruction both directly, through tissue invasion and the production of harmful substances, or indirectly,by activation of host defense mechanisms, creating an inflammatory infiltrate of potent catabolic activitythat can interfere with normal host defense mechanisms. In response to the aggression, host defense mechanismsactivate innate and adaptive immune responses. Our aim is to offer a general overview of the main mechanismsinvolved in the host response to bacterial aggression in periodontitis, such as lipopolysaccharide receptor CD14,complement system, polymorphonuclear neutrophils, antibodies and immunoglobulins (AU)

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Problem-based learning versus lectures: Comparison of academic results andtime devoted by teachers in a course on Dentistry in Special Patients

Objectives: Problem-Based Learning (PBL) is a teaching-learning technique centred on the complete developmentof the student. It has been successfully implemented in several universities, notably in the health sciences. Theprocess of creating the European Higher Education Area, initiated in Bologna, encourages European universitiesto use new methodologies in the teaching-learning process, including PBL. Our objectives were to analyze theresults obtained by using PBL with fifth-year Dentistry students. Study design: Comparison of academic resultsbetween students receiving lectures and PBL participants, and assessment of differences between them in the timedevoted to tasks by students and teachers. Results: PBL participants obtained higher grades compared to thosereceiving lectures only(p<0.05). The two student groups devoted the same amount of time to this subject but thetime distribution of tasks was very different, with PBL students spending more time on group work and analysisof the literature. The teachers devoted much more time to the PBL group. Conclusions: PBL is a teaching-learningmethodology that improves student academic results. PBL diverts student time to more complex tasks but requiresa greater commitment from the teachers (AU)

Host defence mechanisms against bacterial aggression in periodontal disease: Basic mechanisms.

Periodontal diseases are complex bacteria-induced infections characterised by an inflammatory host response to plaque microbiota and their by-products. Most of these microorganisms have virulence factors capable of causing massive tissue destruction both directly, through tissue invasion and the production of harmful substances, or indirectly, by activation of host defense mechanisms, creating an inflammatory infiltrate of potent catabolic activity that can interfere with normal host defense mechanisms. In response to the aggression, host defense mechanisms activate innate and adaptive immune responses. Our aim is to offer a general overview of the main mechanisms involved in the host response to bacterial aggression in periodontitis, such as lipopolysaccharide receptor CD14, complement system, polymorphonuclear neutrophils, antibodies and immunoglobulins.

Problem-based learning versus lectures: comparison of academic results and time devoted by teachers in a course on Dentistry in Special Patients.

OBJECTIVES: Problem-Based Learning (PBL) is a teaching-learning technique centred on the complete development of the student. It has been successfully implemented in several universities, notably in the health sciences. The process of creating the European Higher Education Area, initiated in Bologna, encourages European universities to use new methodologies in the teaching-learning process, including PBL. Our objectives were to analyze the results obtained by using PBL with fifth-year Dentistry students. STUDY DESIGN: Comparison of academic results between students receiving lectures and PBL participants, and assessment of differences between them in the time devoted to tasks by students and teachers. RESULTS: PBL participants obtained higher grades compared to those receiving lectures only (p<0.05). The two student groups devoted the same amount of time to this subject but the time distribution of tasks was very different, with PBL students spending more time on group work and analysis of the literature. The teachers devoted much more time to the PBL group. CONCLUSIONS: PBL is a teaching-learning methodology that improves student academic results. PBL diverts student time to more complex tasks but requires a greater commitment from the teachers.

Analysis of new diagnostic methods in suspicious lesions of the oral mucosa

Objective: The objective of this study was to analyse publications related to examination techniques that might improve the visualisation of suspicious lesions of the oral mucosa (ViziLite® system and VELscope® system) or that might facilitate the cytological identification of suspicious lesions (OralCDx®). Methods: A literature search was performed, using the PubMed database and the key words “brush biopsy”, “Oral- CDx”, “ViziLite” and “Velscope”, limiting the search to papers in English or Spanish published from 2002 to 2008. Results: According to the results of studies identified, the ViziLite® system has a sensitivity of 100% and specificity ranging from 0-14.2%, the VELscope® system has a sensitivity of 98-100% and specificity of 94-100% and the Oral CDx® system has a sensitivity of 71.4-100% and specificity of 32-100%. Conclusion: Clinical examination and histopathological confirmation with biopsy remain the gold standard for the detection of oral cancer. More randomised controlled studies are needed to confirm the positive cost-benefit relationship and the true usefulness of these “new diagnostic methods” in oral mucosal pathology (AU)

Analysis of new diagnostic methods in suspicious lesions of the oral mucosa.

OBJECTIVE: The objective of this study was to analyse publications related to examination techniques that might improve the visualisation of suspicious lesions of the oral mucosa (ViziLite system and VELscope system) or that might facilitate the cytological identification of suspicious lesions (OralCDx). METHODS: A literature search was performed, using the PubMed database and the key words "brush biopsy", "OralCDx", "ViziLite" and "Velscope", limiting the search to papers in English or Spanish published from 2002 to 2008. RESULTS: According to the results of studies identified, the ViziLite system has a sensitivity of 100% and specificity ranging from 0-14.2%, the VELscope system has a sensitivity of 98-100% and specificity of 94-100% and the Oral CDx system has a sensitivity of 71.4-100% and specificity of 32-100%. CONCLUSION: Clinical examination and histopathological confirmation with biopsy remain the gold standard for the detection of oral cancer. More randomised controlled studies are needed to confirm the positive cost-benefit relationship and the true usefulness of these "new diagnostic methods" in oral mucosal pathology.

Relationship between oral Kaposi 's sarcoma and HAART: contribution of two case reports.

Two HIV infected patients not receiving Highly Active Antiretroviral Treatment (HAART) presented with epidemic Kaposi's sarcoma of the oral cavity. One patient initially refused HAART, but when the lesion became large enough to be noticeable he agreed to HAART associated with excision of the intraoral lesion by CO2 laser. The other patient developed KS and progressed to AIDS at two years after ceasing HAART due to adverse effects; he was referred to hospital for renewed administration of HAART. In both cases, the lesions observed in the oral cavity were the first clinical manifestation of AIDS. These reports underline the close relationship between the use of HAART and the control of KS lesions, highlighting the important role of the dentist in the identification and early diagnosis of these oral lesions.

Relationship between oral Kaposi ’s sarcoma and HAART: Contribution of two case reports

Two HIV infected patients not receiving Highly Active Antiretroviral Treatment (HAART) presented with epidemicKaposi’s sarcoma of the oral cavity. One patient initially refused HAART, but when the lesion became large enoughto be noticeable he agreed to HAART associated with excision of the intraoral lesion by CO2 laser. The other patientdeveloped KS and progressed to AIDS at two years after ceasing HAART due to adverse effects; he was referred tohospital for renewed administration of HAART. In both cases, the lesions observed in the oral cavity were the firstclinical manifestation of AIDS. These reports underline the close relationship between the use of HAART and thecontrol of KS lesions, highlighting the important role of the dentist in the identification and early diagnosis of these oral lesions (AU)

Cellular senescence in oral cancer and precancer and treatment implications: a review.

INTRODUCTION: Recent studies have demonstrated the capacity of the human organism to prevent the growth of potentially carcinogenic cells by paralyzing them. This antitumor mechanism is known as cellular senescence and is defined as an emergency defence system for cells on the way to becoming cancerous. RESULTS: This review of the literature suggests that oncogene-induced senescence may be a response to oncogenic activation, acting as a natural barrier against tumorigenesis at a premalignant stage. Thus, a large number of cells enter senescence in premalignant lesions but none do so in malignant tumors, due to the loss of senescent pathway effectors such as p16(INK4a) or ARF-p53. Potential senescence markers in oral precancerous lesions include p21(WAF1), p16(INK4a), pRb, Maspin, RAR-beta, G-actin, p15(INK4b), DCR2, and DEC1, some of which are currently under study. CONCLUSION: In the short term, the study of this mechanism may yield valuable data for the management of oral cancer and precancer, for which no effective diagnostic or prognostic markers are yet available.

Implications of prion diseases for dentistry: an update.

Prions are normal proteins present in all mammals, especially in the central nervous system (CNS) and lymphoreticular tissue. Their transformation into a highly infectious molecule gives rise to a group of diseases known as transmissible spongiform encephalopathies (TSEs), which cause vacuolar degeneration of gray matter and produce a fatal neurodegenerative disorder. Prion diseases have attracted considerable attention in recent years, and this review of the literature was designed to determine their implications for dentistry, studying the possibility of cross-transmission in the dental office and describing their oral manifestations. The main oral manifestations are dysphagia, dysarthria, paresthesias, dysesthesias, and dysgeusia. The most frequently involved oral tissues are the trigeminal ganglion, posterior third of the tongue, tonsils, and, much less commonly, alveolar nerves, gingiva, and salivary glands. Although no contagion has been reported in the dental setting to date, prions resist the usual dental sterilization systems and transmission of this type of disease remains a potential risk. It is therefore important for dentists to be aware of these diseases, to identify high-risk patients by obtaining an adequate clinical history, and to know the appropriate procedures to be followed.

Gene therapy in the management of oral cancer: review of the literature.

Gene therapy essentially consists of introducing specific genetic material into target cells without producing toxic effects on surrounding tissue. Advances over recent decades in the surgical, radiotherapeutic and chemotherapeutic treatment of oral cancer patients have not produced a significant improvement in patient survival. Increasing interest is being shown in developing novel therapies to reverse oral epithelial dysplastic lesions. This review provides an update on transfer techniques, therapeutic strategies, and the clinical applications and limitations of gene therapy in the management of oral cancer and precancer. We highlight the combination of gene therapy with chemotherapy (e.g., 5-Fluoracil) and immunotherapy, given the promising results obtained in the use of adenovirus to act at altered gene level (e.g., p53). Other techniques such as suicide gene therapy, use of oncolytic viruses or the use of antisense RNA have shown positive although very preliminary results. Therefore, further research into these promising gene therapy techniques is required to assess their true efficacy and safety in the management of these lesions.