Faculty Bibliography

Oral melanoacanthoma (MA) is a rare, benign pigmented lesion that presents as a painless, rapidly growing, brown-black macular lesion that commonly affects the buccal mucosa in areas that are subject to chronic trauma/irritation.1,2 MA is commonly seen in the third and fourth decades of life and primarily affects blacks with a strong female predilection.3,4 Histopathologically, the lesions exhibit proliferation of keratinocytes and dendritic melanocytes.5 This report includes two cases of oral melanoacanthoma and a review of the literature. Case 1: A 43-year-old black female presented with a slowly enlarging pigmented lesion on the right buccal mucosa. The patient did not recall any known trauma to the area or previous infection and reported that the lesion was painless but had a gradually increased in size. Oral examination revealed a 2.0 x 2.0 cm. brown macule on the right buccal mucosa. A punch biopsy was taken of the pigmented area. The tissue was placed in 10% formalin and submitted for microscopic examination. The tissue was stained with hematoxylin and eosin and exhibited acanthotic, stratified squamous epithelium with dendritic melanocytes dispersed throughout the epithelium consistent with a diagnosis of melanoacanthoma. Case 2: A-35 year-old black female presented with a rapidly growing pigmented lesion on the left buccal mucosa. Two years prior to presentation the patient had noted a brown lesion on the buccal mucosa adjacent to a fractured tooth. The lesion remained unchanged and asymptomatic for approximately two years. One week prior to presentation, the patient noted that the lesion was enlarging, but remained painless. Oral examination revealed a 1.5 x 1.5 cm. brown macule surrounded by erythema on the left buccal mucosa adjacent to a fractured tooth. A punch biopsy was taken that included both the pigmented and erythematous areas. The tissue was placed in 10% formalin and submitted for microscopic examination. The tissue was stained with hematoxylin and eosin and exhibited similar histopathologic features to the previous case. Immunohistochemical staining with S-100 and Melan-A dramatically demonstrated the dendritic melanocytes. Review of the literature revealed a total of 50 cases of oral melanoacanthoma. These lesions were reported in black females on the buccal mucosa with subsequent resolution. The cases here demonstrate similar clinical features and age at presentation to previously reported cases. The pathogenesis of oral MA remains unclear, however, most studies suggest this is a reactive process due to chronic irritation.2 Oral MA may regress following biopsy and no surgical intervention is required due to its selfresolving quality.5

Despite significant advances in surgical procedures and treatment, long-term prognosis for patients with oral cancer remains poor, with survival rates among the lowest of major cancers. Better methods are desperately needed to identify potential malignancies early when treatments are more effective. OBJECTIVE: To develop robust classification models from cytology-on-a-chip measurements that mirror diagnostic performance of gold standard approach involving tissue biopsy. MATERIALS AND METHODS: Measurements were recorded from 714 prospectively recruited patients with suspicious lesions across 6 diagnostic categories (each confirmed by tissue biopsy -histopathology) using a powerful new 'cytology-on-a-chip' approach capable of executing high content analysis at a single cell level. Over 200 cellular features related to biomarker expression, nuclear parameters and cellular morphology were recorded per cell. By cataloging an average of 2000 cells per patient, these efforts resulted in nearly 13 million indexed objects. RESULTS: Binary "low-risk"/"high-risk" models yielded AUC values of 0.88 and 0.84 for training and validation models, respectively, with an accompanying difference in sensitivity+specificity of 6.2%. In terms of accuracy, this model accurately predicted the correct diagnosis approximately 70% of the time, compared to the 69% initial agreement rate of the pool of expert pathologists. Key parameters identified in these models included cell circularity, Ki67 and EGFR expression, nuclear-cytoplasmic ratio, nuclear area, and cell area. CONCLUSIONS: This chip-based approach yields objective data that can be leveraged for diagnosis and management of patients with PMOL as well as uncovering new molecular-level insights behind cytological differences across the OED spectrum.

This literature review addresses the attempted interventions for the management of oral submucous fibrosis. The literature supports the use of several medical interventions, including micronutrients, antioxidants, proteolytic enzymes, immune modulators (mainly steroids), and agents to promote blood flow. However, the numbers of reported randomized controlled trials are limited. Therefore, no recommendation can be made for any specific intervention. Until now, no single molecular pathway has been identified that is either necessary or sufficient for the development of fibrosis. This has been a bar for any molecular-targeted therapies. Because areca nut (an ingredient of betel quid) plays a major etiologic role in oral submucous fibrosis, cessation of areca nut use remains pivotal in the management of this disorder.

BACKGROUND: Oral leukoplakia is a relatively common oral lesion that, in a small proportion of people, precedes the development of oral cancer. Most leukoplakias are asymptomatic; therefore, the primary objective of treatment should be to prevent onset of cancer. This review updates our previous review, published in 2006. OBJECTIVES: To assess the effectiveness, safety and acceptability of treatments for leukoplakia in preventing oral cancer. SEARCH METHODS: We searched the following electronic databases: Cochrane Oral Health's Trials Register (to 16 May 2016), the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library, 2016, Issue 4), MEDLINE Ovid (1946 to 16 May 2016), Embase Ovid (1980 to 16 May 2016) and CancerLit via PubMed (1950 to 16 May 2016). We searched the metaRegister of Controlled Trials (to 10 February 2015), ClinicalTrials.gov (to 16 May 2016) and the World Health Organization (WHO) International Clinical Trials Registry Platform for ongoing trials (to 16 May 2016). We placed no restrictions on the language or date of publication when searching electronic databases. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that enrolled people with a diagnosis of oral leukoplakia and compared any treatment versus placebo or no treatment. DATA COLLECTION AND ANALYSIS: We collected data using a data extraction form. Oral cancer development, demonstrated by histopathological examination, was our primary outcome. Secondary outcomes were clinical resolution of the lesion, improvement of histological features and adverse events. We contacted trial authors for further details when information was unclear. When valid and relevant data were available, we conducted a meta-analysis of the data using a fixed-effect model when we identified fewer than four studies with no heterogeneity. For dichotomous outcomes, we calculated risk ratios (RRs) and 95% confidence intervals (CIs). We assessed risk of bias in studies by using the Cochrane tool. We assessed the overall quality of the evidence by using standardised criteria (Grades of Recommendation, Assessment, Development and Evaluation Working Group (GRADE)). MAIN RESULTS: We included 14 studies (909 participants) in this review. Surgical interventions, including laser therapy and cryotherapy, have never been studied by means of an RCT that included a no treatment or placebo arm. The included trials tested a range of medical and complementary treatments, in particular, vitamin A and retinoids (four studies); beta carotene or carotenoids (three studies); non-steroidal anti-inflammatory drugs (NSAIDs), specifically ketorolac and celecoxib (two studies); herbal extracts (four studies), including tea components, a Chinese herbal mixture and freeze-dried black raspberry gel; bleomycin (one study); and Bowman-Birk inhibitor (one study).We judged one study to be at low risk of bias, seven at unclear risk and six at high risk. In general, we judged the overall quality of the evidence to be low or very low, so findings are uncertain and further research is needed.Five studies recorded cancer incidence, only three of which provided useable data. None of the studies provided evidence that active treatment reduced the risk of oral cancer more than placebo: systemic vitamin A (RR 0.11, 95% CI 0.01 to 2.05; 85 participants, one study); systemic beta carotene (RR 0.71, 95% CI 0.24 to 2.09; 132 participants, two studies); and topical bleomycin (RR 3.00, 95% CI 0.32 to 27.83; 20 participants, one study). Follow-up ranged between two and seven years.Some individual studies suggested effectiveness of some proposed treatments, namely, systemic vitamin A, beta carotene and lycopene, for achieving clinical resolution of lesions more often than placebo. Similarly, single studies found that systemic retinoic acid and lycopene may provide some benefit in terms of improvement in histological features. Some studies also reported a high rate of relapse.Side effects of varying severity were often described; however, it seems likely that interventions were well accepted by participants because drop-out rates were similar between treatment and control groups. AUTHORS' CONCLUSIONS: Surgical treatment for oral leukoplakia has not been assessed in an RCT that included a no treatment or placebo comparison. Nor has cessation of risk factors such as smoking been assessed. The available evidence on medical and complementary interventions for treating people with leukoplakia is very limited. We do not currently have evidence of a treatment that is effective for preventing the development of oral cancer. Treatments such as vitamin A and beta carotene may be effective in healing oral lesions, but relapses and adverse effects are common. Larger trials of longer duration are required to properly evaluate the effects of leukoplakia treatments on the risk of developing oral cancer. High-quality research is particularly needed to assess surgical treatment and to assess the effects of risk factor cessation in people with leukoplakia.

Oral mucositis (OM) is among the most common, painful, and debilitating toxicities of cancer regimen-related treatment, resulting in the formation of ulcers, which are susceptible to increased colonization of microorganisms. Novel discoveries in OM have focused on understanding the host-microbial interactions, because current pathways have shown that major virulence factors from microorganisms have the potential to contribute to the development of OM and may even prolong the existence of already established ulcerations, affecting tissue healing. Additional comprehensive and disciplined clinical investigation is needed to carefully characterize the relationship between the clinical trajectory of OM, the local levels of inflammatory changes (both clinical and molecular), and the ebb and flow of the oral microbiota. Answering such questions will increase our knowledge of the mechanisms engaged by the oral immune system in response to mucositis, facilitating their translation into novel therapeutic approaches. In doing so, directed clinical strategies can be developed that specifically target those times and tissues that are most susceptible to intervention.

OBJECTIVE: To perform a systematic review of the pathogenesis of medication-induced salivary gland dysfunction (MISGD). MATERIALS AND METHODS: Review of the identified papers was based on the standards regarding the methodology for systematic reviews set forth by the World Workshop on Oral Medicine IV and the PRISMA statement. Eligible papers were assessed for both the degree and strength of relevance to the pathogenesis of MISGD as well as on the appropriateness of the study design and sample size. A total of 99 papers was retained for the final analysis. RESULTS: MISGD in human studies was generally reported as xerostomia (the sensation of oral dryness) without measurements of salivary secretion rate. Medications may act on the central nervous system (CNS) and/or at the neuroglandular junction on muscarinic, alpha-and beta-adrenergic receptors and certain peptidergic receptors. The types of medications that were most commonly implicated for inducing salivary gland dysfunction were those acting on the nervous, cardiovascular, genitourinary, musculo-skeletal, respiratory, and alimentary systems. CONCLUSIONS: Although many medications may affect the salivary flow rate and composition, most of the studies considered only xerostomia. Thus, further human studies are necessary to improve our understanding of the association between MISGD and the underlying pathophysiology

Oral medicine (stomatology) is a recognized and increasingly important dental specialty in many parts of the world that recognizes and fosters the interplay between medical health and oral health. Its dental activities rely greatly on the underlying biology of disease and evidence-based outcomes. However, full recognition of the importance of oral medicine to patient care, research, and education is not yet totally universally acknowledged. To address these shortcomings, we outline the birth, growth, and future of oral medicine globally, and record identifiable past contributions to the development of the specialty, providing an accurate, unique, and valuable resource on oral medicine. Although it was challenging to gather the data, we present this information as a review that endeavors to summarize the salient points about oral medicine, based on MEDLINE, other internet searches, communication with oral medicine and stomatological societies across the world, the web page http://en.wikipedia.org/wiki/List_of_dental_organizations, and discussions with a wide range of key senior persons in the specialty.

Introduction: Oral mucositis (OM) is among the most common, painful and debilitating toxicities of cancer regimen-related treatment, resulting in the formation of ulcers, which are susceptible to increased colonization of microorganisms. Objectives: The aim of this study is to explore the changes in the microbiome associated with OM onset in head and neck cancer patients (oral cavity and oropharynx squamous cell carcinoma) undergoing radiotherapy alone (RT) or chemoradiotherapy (chemoRT) using molecular techniques. Methods: We recruited patients scheduled for receiving radiotherapy alone or chemoRT. Site-specific oral biofilms samples were collected using Isohelix swabs at two time points: before initiating RT/ChemoRT (pre-OM), and at the onset of OM (post-OM ie OM > 1, WHO scale). Changes in microbial abundance were detected using the Human Oral Microbe Identification using Next Generation Sequencing (HOMINGS) and metagenomic analyses. An integrative computational model estimated average changes of microbial abundance patterns of 768 species identified from pre-and-post OM onset. Results: Relative changes in abundance of 54 microbial biomarkers in 16 subjects were discriminative between pre and post OM onset. Discriminant species such as Gemella haemolysans, Granulicatella elegans, Haemophilus spp., Prevotellaoris, and Aggregatibacter sp. HOT512 were found to be significantly overabundant in post-OM onset samples as compared to pre-OM. (Table Presented) Conclusions: Our results suggest a dynamic shift in the oral microbiome during the onset of OM. These species may act as opportunistic pathogens in this population, and further investigation is warranted to explore if they facilitate further tissue damage and subsequent pain