Rui Amaral Mendes

Characterization and management of the keratocystic odontogenic tumor in relation to its histopathological and biological features

Keratocystic odontogenic tumor (KCOT), formerly referred to as odontogenic keratocyst, is a benign neoplasm of odontogenic origin which may present an aggressive and infiltrative behavior leading to high recurrence rates. A review of the various treatment modalities, ranging from simple enucleation to radical surgery is portrayed in relation to clinical, radiological, histopathological and molecular features. Although prognostic factors based on clinico-pathologic and immunohistochemical findings for determining the potential for recurrence of KCOT still remains unclear, its use for determining the potential for recurrence of KCOT after surgical treatment may become important to successfully manage this neoplasms aggressive behavior. The key element for future management of KCOTs will probably be based on thorough knowledge of the biological basis of this tumor, thereby enabling a more tailored treatment approach.

Genetics/epigenetics of oral premalignancy: current status and future research*

Squamous cell carcinoma (SCC) of the oral and oropharyngeal region is the sixth most common malignancy in the world today. Despite numerous advances in treatment, long-term survival from this disease remains poor. Early detection can decrease both morbidity and mortality associated with this neoplasm. However, screening for potentially malignant disease is typically confounded by difficulty in discriminating between reactive/inflammatory lesions vs those lesions that are premalignant in nature. Furthermore, the histologic diagnosis of dysplasia can be subjective and is thus prone to a considerable range of interpretation. Similarly, no definitive, validated criteria exist for predicting which dysplastic lesions are most likely to progress to cancer over time. Given this state of science, the presence of dysplasia can only be used to indicate that an oral lesion may have an increased risk of malignant transformation. Molecular biomarkers capable of identifying the subset of lesions likely to progress to cancer are required to eliminate this clinical diagnostic dilemma. The purpose of this review is to assess the current state of knowledge regarding genetic/epigenetic alterations observed in oral mucosal premalignancy. In addition, recommendations for future research studies directed at defining the predictive capacity of specific biomarkers in this modeling are presented.

Recurrence rate of keratocystic odontogenic tumor after conservative surgical treatment without adjunctive therapies – A 35-year single institution experience

The recurrence rate in conservative surgical treatment, without adjunctive treatment, of the keratocystic odontogenic tumor (KCOT) has been studied. A total number of 68 patients, previously untreated and fulfilling the histopathological criteria provided by the 2005 WHO classification, has been retrospectively reviewed. The study period lasted from 1975 to 2009. Treatment consisted of enucleation (n=58) or marsupialization (n=10). The mean follow-up period was 65 months. No involved or adjacent teeth were removed, except for wisdom teeth, if applicable, and badly decayed teeth. After enucleation, the recurrence rate was 20.7% in a mean follow-up period of 46 months, while 40% of the marsupialized KCOTs recurred in a mean follow-up period of 58 months. In none of the patients permanent loss of nerve function has been observed. Due to the recurrence rate observed in the present study, and in view of the potential benefit of adjunctive treatment in KCOT, particularly with regard to the use of Carnoys solution, there is a need for prospective studies to test its usefulness with regard to the risk of recurrences.

An overview on the expression of cyclooxygenase-2 in tumors of the head and neck.

Cyclooxygenase-2 (COX-2) levels are increased in various tumors, particularly those involving the esophagus, stomach, breast, pancreas, lung, colon, skin, urinary bladder, prostate and head and neck. Nevertheless, the tumorigenic mechanisms of COX-2 overexpression still remain poorly understood and may include mechanisms that may act at different stages of the disease. Thus, the literature shows increasing evidence that overexpression of the COX-2 plays an important role in tumor growth and spread of tumors by interfering with different biological processes such as cell proliferation, cellular adhesion, immune surveillance, apoptosis, and angiogenesis. Furthermore, the expression of COX-2 might shed some light over the physiopathology and clinical behavior of tumors of the head and neck, including benign odontogenic neoplasms of the jaws with an aggressive behavior, such as keratocystic odontogenic tumors (KCOT). Ultimately, the research of molecular markers associated with the biological behavior of tumors will help to understand the underlying molecular mechanisms and to predict the clinical outcome, leading to the development of new therapeutic applications, such as molecular-targeted treatment and patient tailored therapy.

A comparative immunohistochemical analysis of COX-2, p53, and Ki-67 expression in keratocystic odontogenic tumors.

OBJECTIVE The aim of the present study was to investigate the association between the expression of cyclooxygenase-2 (COX-2) in keratocystic odontogenic tumors (KCOT) and more commonly used markers, such as p53 and Ki-67. STUDY DESIGN Expression of cyclooxygenase-2 (COX-2) in 20 biopsy specimens of keratocystic odontogenic tumors (KCOT) has been analyzed and compared with the expression of previously reported markers Ki-67 and p53. Formalin-fixed, paraffin-embedded blocks were sectioned and used for hematoxylin-eosin (H&E) staining and incubated with anti-cox-2, anti-ki-67, and anti-p53 monoclonal antibodies for immunohistochemical examination. Detection of the COX-2 antibody was performed with the EnVision kit. Cellular staining pattern was cytoplasmatic for COX-2 and nuclear for both Ki-67 and p-53. Molecular expressions were semiquantitatively evaluated as negative (-), mild (±) or strong (+). RESULTS Mild to strong expression of COX-2 was observed in 20 (100%) of the cases. Fifteen (75%) of the KCOTs stained positive for p53 and 18 (90%) stained positive for Ki-67. There was no statistically relevant difference between the expressions of COX - 2, Ki-67, and p53. CONCLUSIONS Although COX-2 has rarely been used to assess the biological activity of the KCOT, the results portrayed in the current study and the current knowledge of the overall role known to be played by COX-2 in tumorigenesis suggest that COX-2 may be an important marker involved in the biological behavior of the KCOT. Larger studies are required to improve our knowledge of the possible role of COX-2 in the pathogenic mechanism involved in KCOT.

The therapeutic effects of apigenin and dexamethasone on 5-fluorouracil-induced oral mucositis - a pilot study using a Syrian hamster model.

OBJECTIVE Oral mucositis (OM) is a common complication of chemotherapy and radiotherapy. The aim of this study was to evaluate the effects of treating 5-fluorouracil-induced OM with apigenin and dexamethasone. METHODS Thirty-six male Syrian hamsters were randomly assigned to one of three groups: control (50% acetic acid + 5-FU), 50% acetic acid + 5-FU + potassium Apigenin (KA), and 50% acetic acid + 5-FU + dexamethasone. The animals from each group were sacrificed 5, 7, 10, and 14 days after inducing the mucositis, and two samples collected from each animal, accounting a total of 72 samples. Macroscopic changes were assessed by histomorphometric analysis, with ulcers being assessed by imaging analysis and the number of inflammatory cells in the ulcerated region quantified in all periods through histomorphometric analysis (H&E). Furthermore, immunohistochemical changes were evaluated by proliferating cell nuclear antigen. RESULTS All groups presented an increased inflammatory infiltrate after 7 days, compared to other evaluation times (P ≥ 0.05). There was significant difference between apigenin and control group in the 10-days period. Lower quantity of inflammatory cells in the apigenin-treated group in comparison with control group in the 7- and 10-days periods was observed (P < 0.05). No statistically significant difference was verified among the groups in 5- and 14-days periods. The healing process of the control group was slower than that of apigenin and dexamethasone-treated groups, with an overall significant difference between apigenin and the control group in the 10-days period. CONCLUSIONS Apigenin treatment may enhance healing of OM induced by 5-fluorouracil, thus suggesting that more extensive research in this area may be useful to assess the role of agents of natural origin capable of preventing OM. Hence, further studies involving broader samples are need to confirm the therapeutic potential shown by this study.

Novel anticoagulants - an update on the latest developments and management for clinicians treating patients on these drugs.

There are several novel anticoagulant agents that are being increasingly used as an alternative to warfarin, with these drugs being reported to be at least as effective if not better. Their increased use means that oral care clinicians should have a sound understanding of the mechanism of action, pharmacology, reversal strategies and management of bleeding in patients taking these drugs. Surprisingly, there is little published in the current literature specific to professionals involved in oral health care. In this review, we provide an overview of these drugs and discuss the management of patients who need an oral procedure based on currently available literature and clinical trials.

Oncogenic Pathways in the Development of Oral Cancer

Abnormality of EGFR gene and overexpression of the protein have been reported in various human tumors, with an abnormal amplification of the EGFR gene being reported in oral squamous cell carcinoma, although not limited to the final stages of the carcinogenic process. In fact, a low level of gene amplification also occurs at a significant frequency in epithelial dysplasia and carcinoma in situ, and, moreover, increased EGFR gene copies via amplification seems to play an important role in the development of invasive cancer [2]. Moreover, the expression of proliferation markers TGF-α and EGFR in cells of the oral epithelium presenting a spectrum of dysplastic changes revealed a serial upregulation both in terms of area and intensity of staining of TGF-α in the epithelial cells of oral precancerous lesions exhibiting features of dysplasia. Likewise, TGF-α expression has been reported higher than EGFR’s in the proliferative pool of the oral epithelium in oral precancer lesions, thus suggesting that an initial upregulation of TGF-α was likely to exert a paracrine effect on the adjacent nonproliferative cells therefore increasing the expression of the cell surface receptor [3]. Significant linear increase in the intensity of staining of EGFR in the differentiated cells of the stratum spinosum in oral leukoplakia with mild epithelial dysplasia has also been reported, which might be explained by the inducing role of TGF-α over DNA synthesis in noncycling cells [3].

Could the PI3K canonical pathway be a common link between chronic inflammatory conditions and oral carcinogenesis

The association between chronic inflammatory disorders and oral carcinogenesis has been both a source of interest and contention. Based upon its central importance in oral carcinogenesis, the finding that the PI3k/Akt/mTOR pathway is activated in oral lichen planus, chronic graft-versus-host disease, and chronic oral candidiasis suggests that it may provide a link between benign and malignant oral conditions. Here, we discuss a possible mechanistic rationale that addresses the activation of this important signaling pathway and its downstream events, while correlating it with the carcinogenic potential of chronic oral disorders.

E-Healthcare Disparities Across Cultures: Infrastructure, Readiness and the Digital Divide

As e-healthcare becomes a reality for healthcare service provision across the world, challenges in acceptance, implementation, usage and effectiveness have begun to emerge. The infrastructure, readiness and literacy levels required for the effective delivery of e-healthcare services may be prohibitive in providing access to those most in need. As research brings to light the real effectiveness of e-healthcare programmes across the globe, this paper explores how e-healthcare has been implemented worldwide and how populations have been served by an innovation in Information Technology and healthcare that has sought to bring health services to remote areas, improve access to healthcare and narrow the divide between healthcare providers and patients. While notable achievements have seen real time clinical data captured and medical records digitalised, the very determinants responsible for actual health and social disparities are equally responsible for disparities is access to e-healthcare.