Summary Type 1 diabetes is a chronic autoimmune disease characterised by insulin deficiency and resultant hyperglycaemia. Knowledge of type 1 diabetes has rapidly increased over the past 25 years, resulting in a broad understanding about many aspects of the disease, including its genetics, epidemiology, immune and β-cell phenotypes, and disease burden. Interventions to preserve β cells have been tested, and several methods to improve clinical disease management have been assessed. However, wide gaps still exist in our understanding of type 1 diabetes and our ability to standardise clinical care and decrease disease-associated complications and burden. This Seminar gives an overview of the current understanding of the disease and potential future directions for research and care.

Type 1 diabetes

Leaving for College

Oral potentially malignant disorders (PMD) are recognisable mucosal conditions that have an unpredictable risk of transformation to squamous cell carcinoma (SCC), a lethal and deforming disease of rising incidence. Contemporary management is based on clinical recognition of suspicious lesions and incisional biopsy to enable histopathological assessment and grading of dysplasia, together with excision of high-risk lesions and long-term surveillance. However, it is impossible to predict clinical outcome or risk of malignant transformation. Our aim was to evaluate the relevance of previously identified oral precursor lesions for the development of SCC and staging of disease. We therefore retrospectively reviewed 1248 cases of SCC diagnosed in oral and maxillofacial surgery units at Newcastle upon Tyne and Sunderland hospitals between 1996 and 2009. Of them, 58 identifiable precursor lesions became malignant but only 25 had been dysplastic on initial biopsy; 19 of 33 non-dysplastic lesions exhibited lichenoid inflammation only. SCC arose most often on the ventrolateral tongue and floor of the mouth, with a mean transformation time of 29.2 months. Transformation time was significantly shorter in men (p=0.018) and those over 70 years of age (p=0.010). Patients who consumed more than 21 units of alcohol/week and those who had had interventional laser surgery to treat precursor lesions, had higher-staged tumours (p=0.048). Although retrospective, this study shows that the results of incisional biopsy and grading of dysplasia have limited use as predictive tools, and supports the view that cancer may arise in the absence of recognisable epithelial dysplasia. Our findings confirm the importance of clinical vigilance and active surveillance in the management of all patients with clinically suspicious oral lesions, irrespective of the histological findings.

Oral precursor lesions and malignant transformation – who, where, what, and when?

Background Oral lichen planus (OLP) is a relatively common chronic T cell-mediated disease, which can cause significant pain, particularly in its erosive or ulcerative forms. As pain is the indication for treatment of OLP, pain resolution is the primary outcome for this review. This review is an update of a version last published in 2011, but focuses on the evidence for corticosteroid treatment only. A second review considering non-corticosteroid treatments is in progress. Objectives To assess the effects and safety of corticosteroids, in any formulation, for treating people with symptoms of oral lichen planus. Search methods Cochrane Oral Health's Information Specialist searched the following databases to 25 February 2019: Cochrane Oral Health's Trials Register, CENTRAL (2019, Issue 1), MEDLINE Ovid, and Embase Ovid. ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform were searched for ongoing trials. There were no restrictions on language or date of publication. Selection criteria We considered randomised controlled clinical trials (RCTs) of any local or systemic corticosteroid treatment compared with a placebo, a calcineurin inhibitor, another corticosteroid, any other local or systemic (or both) drug, or the same corticosteroid plus an adjunctive treatment. Data collection and analysis Three review authors independently scanned the titles and abstracts of all reports identified, and assessed risk of bias using the Cochrane tool and extracted data from included studies. For dichotomous outcomes, we expressed the estimates of effects of an intervention as risk ratios (RR), with 95% confidence intervals (CI). For continuous outcomes, we used mean differences (MD) and 95% CI. The statistical unit of analysis was the participant. We conducted meta-analyses only with studies of similar comparisons reporting the same outcome measures. We assessed the overall certainty of the evidence using GRADE. Main results We included 35 studies (1474 participants) in this review. We assessed seven studies at low risk of bias overall, 11 at unclear and the remaining 17 studies at high risk of bias. We present results for our main outcomes, pain and clinical resolution measured at the end of the treatment course (between one week and six months), and adverse effects. The limited evidence available for comparisons between different corticosteroids, and corticosteroids versus alternative or adjunctive treatments is presented in the full review. Corticosteroids versus placebo Three studies evaluated the effectiveness and safety of topical corticosteroids in an adhesive base compared to placebo. We were able to combine two studies in meta-analyses, one evaluating clobetasol propionate and the other flucinonide. We found low-certainty evidence that pain may be more likely to be resolved when using a topical corticosteroid rather than a placebo (RR 1.91, 95% CI 1.08 to 3.36; 2 studies, 72 participants; I² = 0%). The results for clinical effect of treatment and adverse effects were inconclusive (clinical resolution: RR 6.00, 95% CI 0.76 to 47.58; 2 studies, 72 participants; I² = 0%; very low-certainty evidence; adverse effects RR 1.48, 95% 0.48 to 4.56; 3 studies, 88 participants, I² = 0%, very low-certainty evidence). Corticosteroids versus calcineurin inhibitors Three studies compared topical clobetasol propionate versus topical tacrolimus. We found very low-certainty evidence regarding any difference between tacrolimus and clobetasol for the outcomes pain resolution (RR 0.45, 95% CI 0.24 to 0.88; 2 studies, 100 participants; I² = 80%), clinical resolution (RR 0.61, 95% CI 0.38 to 0.99; 2 studies, 52 participants; I² = 95%) and adverse effects (RR 0.05, 95% CI 0.00 to 0.83; 2 studies, 100 participants; very low-certainty evidence) . One study (39 participants) compared topical clobetasol and ciclosporin, and provided only very low-certainty evidence regarding the rate of clinical resolution with clobetasol (RR 3.16, 95% CI 1.00 to 9.93), pain resolution (RR 2.11, 95% CI 0.76 to 5.86) and adverse effects (RR 6.32, 95% CI 0.84 to 47.69). Two studies (60 participants) that compared triamcinolone and tacrolimus found uncertain evidence regarding the rate of clinical resolution (RR 0.86, 95% CI 0.55 to 1.35; very low-certainty evidence) and that there may be a lower rate of adverse effects in the triamcinolone group (RR 0.47, 95% CI 0.22 to 0.99; low-certainty evidence). These studies did not report on pain resolution. Authors' conclusions Corticosteroids have been first line for the treatment of OLP. This review found that these drugs, delivered topically as adhesive gels or similar preparations, may be more effective than placebo for reducing the pain of symptomatic OLP; however, with the small number of studies and participants, our confidence in the reliability of this finding is low. The results for clinical response were inconclusive, and we are uncertain about adverse effects. Very low-certainty evidence suggests that calcineurin inhibitors, specifically tacrolimus, may be more effective at resolving pain than corticosteroids, although there is some uncertainty about adverse effects and clinical response to tacrolimus showed conflicting results.

/pdf/interventions-for-treating-oral-lichen-planus-corticosteroid-2h20xlgix5.pdf

Interventions for treating oral lichen planus: corticosteroid therapies.

ObjectiveProliferative verrucous leukoplakia (PVL) is a rare and recalcitrant form of leukoplakia. The purpose of this review is to further characterize the risk factors, clinical course, and optimal treatment for this highly aggressive, premalignant lesion.Data SourcesTwenty-six articles on PVL with a total of 329 PVL cases.Review MethodsA systematic review of the literature using Ovid, PubMed, Cochrane Database, and gray literature was conducted of all PVL cases reported between 1985 and 2014. Inclusion criteria required reporting of patient follow-up and recurrence rates. Data were analyzed using descriptive statistics. Student t test and Fisher exact test were used to identify factors associated with malignant transformation.ResultsThe mean patient age was 63.9 years. Most patients were female (66.9%) and nontobacco users (65.22%). Mean follow-up was 7.4 years, with an average of 9.0 biopsies per patient during this period. Proliferative verrucous leukoplakia exhibited histopathologic features along a...

http://journals.sagepub.com/doi/pdf/10.1177/0194599815586779

Optimal Management of Proliferative Verrucous Leukoplakia: A Systematic Review of the Literature.

White lesions both physiologic as well as pathologic are relatively frequent in the oral cavity, the most common pathology being oral leukoplakia (OL). There are many variants of OL, one of which is oral proliferative verrucous leukoplakia (OPVL). OPVL is a rare clinico-pathological entity, which is slow growing, long-term progressive lesion, but remains an enigmatic and difficult to define. The etiology of OPVL remains still unclear. Tobacco use does not seem to have a significant influence on the appearance of OPVL. These lesions may occur both in smokers and non-smokers. It is observed more frequently in women and elderly patients over 60 years at the time of diagnosis. The buccal mucosa and tongue are the most frequently involved sites. It develops initially as a white plaque of hyperkeratosis that eventually becomes a multifocal disease with confluent, exophytic and proliferative features. Various published case series have presented OPVL as a disease with aggressive biological behavior due to its high probability of recurrence and a high rate of malignant transformation. Prognosis is poor for this seemingly harmless-appearing white lesion of the oral mucosa. This article describes the clinical aspects and histologic features of an OPVL case that demonstrated the typical behavior pattern in a long-standing, persistent lesion and discusses this relatively rare entity in light of current information.

Oral proliferative verrucous leukoplakia: A case report with an update.

Background and Aim
As far as research regarding any disease is concerned, each and every aspect poses a challenge. One such entity that poses a challenge in our arena is oral submucous fibrosis (OSF) as no effective treatment is available for this progressively disabling condition with high malignant potential. Hence the present study was undertaken with the aim to determine the use of pentoxifylline (PTX) on the clinical and histopathologic course of OSF.

/pdf/pentoxifylline-in-patients-with-oral-submucous-fibrosis-a-45kbu02a7k.pdf

Pentoxifylline in Patients with Oral Submucous Fibrosis—A Randomized Clinical Trial

Aim Oral lichen planus (OLP) is a chronic mucocutaneous disorder seen in clinical dental practice. Despite the progress in research and advances in knowledge, the successful management of OLP is still difficult to achieve. The aim of the present study was to compare the therapeutic effects of triamcinolone (TA) preparation (0.1%) with hyaluronic acid (HA) preparation (0.2%) in the management of OLP. Methods In total, 40 patients of any age or sex who had symptomatic OLP were selected and randomly divided into two groups. Group I received topical 0.1% TA, and group II received topical 0.2% HA preparation three times per day for a period of 4 weeks. Basement data were recorded for each patient. Patients were evaluated on days 14 and 21, and after completing the course of treatment. The visual analog scale (VAS) was used for evaluating pain and burning sensation, along with an evaluation of the degree of erythema and mean area of the lesion. Data were analyzed by SPSS 17.0 software using Mann-Whitney and t test. P ≤ 0.05 was considered statistically significant. Results Our results showed considerable improvement in all of the parameters evaluated. Baseline characteristics, including pain score, size, and clinical characteristics of the lesions, were not different between the two treatment groups. Both TA and HA were found to reduce the VAS score, the degree of erythema, and size of the lesions after treatment. Conclusion The application of HA is suggested, and is an effective substitute for TA in the treatment of OLP.

Topical hyaluronic acid in the management of oral lichen planus: A comparative study

Objectives. To assess the changing mid-face fracture patterns using a computed tomography scan. Methodology: Fifty patients with mid-face trauma requiring open reduction and fixation were studied using 1.6 mm axial, sagittal, coronal and 3D images. Images were evaluated clinically, intra-operatively and finally were compared with standard Le Fort lines. Results. The male population dominated the female at a ratio of 11.5:1. The majority of the mid-face fractures were seen in the age group of 21–30 years. Road traffic accident (78%) was the major etiological factor followed by work-related accidents (12%) and assaults (10%). The CT scan analysis included categorizing the patients into three groups: (1) Fracture patterns resembling Le Fort lines (24%); (2) Fracture patterns partially resembling Le Fort lines (56%); and (3) Fracture patterns that do not resemble Le Fort lines (20%). Conclusion. With the change in the velocity of wounding object, there is a change in the mid-face fracture patterns. T...

Assessment of changing patterns of Le fort fracture lines using computed tomography scan: an observational study

Odontomas are thought to be hamartomatous malformations in which enamel, dentin, and pulp, and occasionally cementum, is present in a disorganized form. It develops by the completely differentiated epithelial and mesenchymal cells that form ameloblasts and odontoblasts respectively. With no gender predilection and often asymptomatic, it is usually discovered accidentally on a routine radiographic study. They may be related with malformation, aplasia, malposition, delayed eruption of associated teeth and sometimes cystic changes. In these cases, Cone Beam Computed Tomography (CBCT) provides several advantages over conventional radiographs regarding diagnosis and treatment planning. Enucleation is the treatment of choice for these tumors and relapse is very uncommon. This paper highlights the etiology, classification, clinical/radiologic/histopathologic features and treatment options available for odontomas. Although much is known about odontomas but sometimes it presents as an enigma to a dental practitioner that needs to be unfolded with the use of radiography that acts as an indispensable tool in routine dental clinical examination.

Namdeo Prabhu

Papers

Oral proliferative verrucous leukoplakia: A case report with an update.

Pentoxifylline in Patients with Oral Submucous Fibrosis—A Randomized Clinical Trial

Topical hyaluronic acid in the management of oral lichen planus: A comparative study

Assessment of changing patterns of Le fort fracture lines using computed tomography scan: an observational study

Odontoma- An Unfolding Enigma