Alexander Ross Kerr

The functions of human saliva: A review sponsored by the World Workshop on Oral Medicine VI

This narrative review of the functions of saliva was conducted in the PubMed, Embase and Web of Science databases. Additional references relevant to the topic were used, as our key words did not generate references which covered all known functions of saliva. These functions include maintaining a moist oral mucosa which is less susceptible to abrasion, and removal of micro-organisms, desquamated epithelial cells, leucocytes and food debris by swallowing. The mucins form a slimy coating on all surfaces in the mouth and act as a lubricant during such processes as mastication, formation of a food bolus, swallowing and speaking. Saliva provides the fluid in which solid tastants may dissolve and distributes tastants around the mouth to the locations of the taste buds. The hypotonic unstimulated saliva facilitates taste recognition. Salivary amylase is involved in digestion of starches. Saliva acts as a buffer to protect oral, pharyngeal and oesophageal mucosae from orally ingested acid or acid regurgitated from the stomach. Saliva protects the teeth against acid by contributing to the acquired enamel pellicle, which forms a renewable lubricant between opposing tooth surfaces, by being supersaturated with respect to tooth mineral, by containing bicarbonate as a buffer and urea and by facilitating clearance of acidic materials from the mouth. Saliva contains many antibacterial, antiviral and antifungal agents which modulate the oral microbial flora in different ways. Saliva also facilitates the healing of oral wounds. Clearly, saliva has many functions which are needed for proper protection and functioning of the human body.

A systematic review of medical interventions for oral submucous fibrosis and future research opportunities.

Oral Diseases (2011) 17 (Suppl. 1), 42-57 Oral submucous fibrosis (OSF) is a chronic, insidious disease caused by areca nut use, and is associated with both significant morbidity (including pain and reduced oral opening) and an increased risk for malignancy. This systematic review explored and updated the current medical (i.e., non-surgical) interventions available for the management of OSF. Of the 27 published medical interventions, there were four randomized controlled trials. The overall quality of these randomized controlled studies was assessed using the GRADE approach and significant limitations that challenged the conclusions were found. However, this review was valuable in terms of identifying opportunities to provide recommendations for future research, in terms of the populations to research, the types of interventions needed, the types of outcomes to be measured, the study designs needed, and the infrastructure required to conduct studies. The next step is to initiate a pathway for a low-cost research plan leading to the development of a brief protocol for future clinical trials in this field, with an emphasis on conducting studies in regions of the world where OSF is prevalent.

Local drug delivery for oral mucosal diseases: challenges and opportunities

There are few topical formulations used for oral medicine applications most of which have been developed for the management of dermatological conditions. As such, numerous obstacles are faced when utilizing these preparations in the oral cavity, namely enzymatic degradation, taste, limited surface area, poor tissue penetration and accidental swallowing. In this review, we discuss common mucosal diseases such as oral cancer, mucositis, vesiculo-erosive conditions, infections, neuropathic pain and salivary dysfunction, which could benefit from topical delivery systems designed specifically for the oral mucosa, which are capable of sustained release. Each condition requires distinct penetration and drug retention profiles in order to optimize treatment and minimize side effects. Local drug delivery may provide a more targeted and efficient drug-delivery option than systemic delivery for diseases of the oral mucosa. We identify those mucosal diseases currently being treated, the challenges that must be overcome and the potential of novel therapies. Novel biological therapies such as macromolecular biological drugs, peptides and gene therapy may be of value in the treatment of many chronic oral conditions and thus in oral medicine if their delivery can be optimized.

World Workshop on Oral Medicine VI: a systematic review of medication-induced salivary gland dysfunction: prevalence, diagnosis, and treatment

ObjectivesMedication-induced salivary gland dysfunction (MISGD) causes significant morbidity resulting in decreased quality of life. This systematic review assessed the literature on the prevalence, diagnosis, treatment, and prevention of MISGD.Materials and methodsElectronic databases were searched for articles related to MISGD through June 2013. Four independent reviewers extracted information regarding study design, study population, interventions, outcomes, and conclusions for each article. Only papers with acceptable degree of relevance, quality of methodology, and strength of evidence were retained for further analysis.ResultsThere were limited data on the epidemiology of MISGD. Furthermore, various methods were used to assess salivary flow rate or xerostomia. Preventive and therapeutic strategies included substitution of medications, oral, or systemic therapy with sialogogues, use of saliva substitutes or of electro-stimulating devices. Although there are promising approaches to improve salivary gland function, most studies are characterized by small numbers and heterogeneous methods.ConclusionsPhysicians and dentists should identify the medications associated with xerostomia and salivary gland dysfunction through a thorough medical history. Preferably, health care providers should measure the unstimulated and stimulated whole salivary flow rates of all their patients so that these values can be used as a baseline to rate the complaints of patients who subsequently claim to experience xerostomia or salivary gland dysfunction as well as the possibilities of effectively treating this condition.Clinical relevanceMISGD remains a major burden for the population. This systematic review provides a contemporary in-depth description of the diagnosis and treatment of MISGD.

Bowman Birk Inhibitor Concentrate and Oral Leukoplakia: A Randomized Phase IIb Trial

Oral premalignancy serves as an ideal model for study of chemopreventive agents. Although 13-cis-retinoic acid showed reversal of oral premalignancy, toxicity, and reversal of clinical response after cessation of therapy obviated its widespread use. A search for nontoxic agents with cancer preventive activity led us to evaluate Bowman Birk Inhibitor (BBI) formulated as BBI Concentrate (BBIC). We previously reported encouraging results in a phase IIa trial of BBIC in patients with oral leukoplakia with measurable clinical responses and favorable biomarker changes. On the basis of these results, we undertook a randomized, placebo controlled phase IIb trial with patients receiving BBIC or placebo for 6 months, with assessment of clinical response and change in lesion area as primary end point and an intent-to-treat analysis. One hundred and thirty two subjects were randomized; and 89 subjects completed six months on study drug or placebo. Both placebo and BBIC showed a statistically significant decrease in mean lesion area of 17.1% and 20.6%, respectively, and partial or greater clinical responses of 30% and 28% respectively. No significant difference between placebo and study drug arms was observed. Histologic review, review of photographs of lesions, and comparison of serum neu protein and oral mucosal cell protease activity also did not show significant differences between study arms. Probable reasons for these negative results were considered, are discussed, and include a placebo with non-BBIC clinical activity and reduced pharmacokinetic availability of the second batch of BBIC. This experience should be a strong cautionary note to those considering “Green” chemoprevention. Cancer Prev Res; 6(5); 410–8. ©2013 AACR.

A Guide to Medications Inducing Salivary Gland Dysfunction, Xerostomia, and Subjective Sialorrhea: A Systematic Review Sponsored by the World Workshop on Oral Medicine VI

BackgroundMedication-induced salivary gland dysfunction (MISGD), xerostomia (sensation of oral dryness), and subjective sialorrhea cause significant morbidity and impair quality of life. However, no evidence-based lists of the medications that cause these disorders exist.ObjectiveOur objective was to compile a list of medications affecting salivary gland function and inducing xerostomia or subjective sialorrhea.Data SourcesElectronic databases were searched for relevant articles published until June 2013. Of 3867 screened records, 269 had an acceptable degree of relevance, quality of methodology, and strength of evidence. We found 56 chemical substances with a higher level of evidence and 50 with a moderate level of evidence of causing the above-mentioned disorders. At the first level of the Anatomical Therapeutic Chemical (ATC) classification system, 9 of 14 anatomical groups were represented, mainly the alimentary, cardiovascular, genitourinary, nervous, and respiratory systems. Management strategies include substitution or discontinuation of medications whenever possible, oral or systemic therapy with sialogogues, administration of saliva substitutes, and use of electro-stimulating devices.LimitationsWhile xerostomia was a commonly reported outcome, objectively measured salivary flow rate was rarely reported. Moreover, xerostomia was mostly assessed as an adverse effect rather than the primary outcome of medication use. This study may not include some medications that could cause xerostomia when administered in conjunction with others or for which xerostomia as an adverse reaction has not been reported in the literature or was not detected in our search.ConclusionsWe compiled a comprehensive list of medications with documented effects on salivary gland function or symptoms that may assist practitioners in assessing patients who complain of dry mouth while taking medications. The list may also prove useful in helping practitioners anticipate adverse effects and consider alternative medications.

An international survey in postgraduate training in Oral Medicine

OBJECTIVES The aim of this preliminary study was to investigate postgraduate Oral Medicine training worldwide and to begin to identify minimum requirements and/or core content for an International Oral Medicine curriculum. MATERIALS AND METHODS Countries where there was believed to be postgraduate training in Oral Medicine were identified by the working group. Standardized emails were sent inviting participants to complete an online survey regarding the scope of postgraduate training in Oral Medicine in their respective countries. RESULTS We received 69 total responses from 37 countries. Of these, 22 countries self-identified as having postgraduate Oral Medicine as a distinct field of study, and they served as the study group. While there is currently considerable variation among Oral Medicine postgraduate training parameters, there is considerable congruency in clinical content of the Oral Medicine syllabi. For example, all of the training programs responded that they did evaluate competence in diagnosis and management of oral mucosal disease. CONCLUSIONS This preliminary study provides the first evidence regarding international Oral Medicine postgraduate training, from which recommendations for an international core curriculum could be initiated. It is through such an initiative that a universal clinical core syllabus in postgraduate Oral Medicine training may be more feasible.

Squamous Cell Carcinoma of the Oral Cavity in Nonsmoking Women: A New and Unusual Complication of Chemotherapy for Recurrent Ovarian Cancer?

PURPOSE To describe occurrences of oral squamous cell carcinoma (SCC) in patients who had received long-term pegylated liposomal doxorubicin (PLD) for ovarian cancer. PATIENTS AND METHODS In our cohort of patients on maintenance PLD for ovarian and related mullerian epithelial malignancies, we encountered two patients with invasive SCC of the oral cavity (one of them multifocal) and one with high-grade squamous dysplasia. Review of patients at our institution receiving PLD for recurrent ovarian cancer identified three additional patients. The duration of treatment, cumulative PLD dose, human papillomavirus (HPV) positivity, BRCA status, stage at diagnosis, outcome, and other characteristics are reviewed. RESULTS All five cases were nonsmokers with no known risk factors for HPV and four were negative for p16 expression. Four of the patients had known BRCA mutations whereas one tested negative. Cumulative doses of PLD were >1,600 mg/m2 given over 30-132 months. Three had SCCs staged as T1N0 oral tongue, alveolar ridge (gingival), and multifocal oral mucosa; one had a T2N0 oral tongue; and one had dysplasia. After excision, two were given radiation but recurred shortly thereafter; the others remain well and have had no further exposure to cytotoxic drugs, including PLD. CONCLUSION Awareness of this possible long-term complication during PLD treatment should enhance the likelihood of early detection of oral lesions in these patients. Decisions to continue maintenance PLD after complete response of the original cancer should perhaps consider the benefits of delaying ovarian cancer recurrence versus the possible risk for a secondary cancer.

World Workshop on Oral Medicine VI: a systematic review of the treatment of mucocutaneous pemphigus vulgaris

OBJECTIVE To determine the efficacy and safety of interventions for pemphigus vulgaris (PV). STUDY DESIGN We conducted a systematic review from 2003 to 2013 according to the Cochrane Collaboration methodology. Randomized controlled trials (RCTs) or controlled clinical trials (CCTs) and observational studies were conducted along with diagnosis confirmed by clinical, histopathologic, and immunofluorescence criteria. Primary outcomes were disease remission and mortality; several relevant secondary outcomes were also included. RESULTS Fourteen RCTs or CCTs and 110 observational studies were included in the final analyses. RCTs or CCTs demonstrated considerable heterogeneity in outcome measures, and all had a high risk of bias for at least 1 of 8 domains. Of the studies, 96.8% (120) described the use of oral corticosteroids. Azathioprine and mycophenolate-mofetil were the most commonly cited treatments. An increasing number of studies described biologic therapies (rituximab, intravenous immunoglobulin [IVIg]). Evidence supporting recent comprehensive treatment guidelines was reviewed. CONCLUSIONS We found persisting wide variations in treatment practice and inadequate quality of research supporting optimal PV treatment.

Evidence-based clinical practice guideline for the evaluation of potentially malignant disorders in the oral cavity: A report of the American Dental Association

BACKGROUND An expert panel convened by the American Dental Association (ADA) Council on Scientific Affairs and the Center for Evidence-Based Dentistry conducted a systematic review and formulated clinical recommendations to inform primary care clinicians about the potential use of adjuncts as triage tools for the evaluation of lesions, including potentially malignant disorders (PMDs), in the oral cavity. TYPES OF STUDIES REVIEWED This is an update of the ADAs 2010 recommendations on the early diagnosis of PMDs and oral squamous cell carcinoma. The authors conducted a systematic search of the literature in MEDLINE and Embase via Ovid and the Cochrane Central Register of Controlled Trials to identify randomized controlled trials and diagnostic test accuracy studies. The authors used the Grading of Recommendations Assessment, Development and Evaluation approach to assess the certainty in the evidence and to move from the evidence to the decisions. RESULTS The panel formulated 1 good practice statement and 6 clinical recommendations that concluded that no available adjuncts demonstrated sufficient diagnostic test accuracy to support their routine use as triage tools during the evaluation of lesions in the oral cavity. For patients seeking care for suspicious lesions, immediate performance of a biopsy or referral to a specialist remains the single most important recommendation for clinical practice. In exceptional cases, when patients decline a biopsy or live in rural areas with limited access to care, the panel suggested that cytologic testing may be used to initiate the diagnostic process until a biopsy can be performed (conditional recommendation, low-quality evidence). CONCLUSIONS AND PRACTICAL IMPLICATIONS The authors urge clinicians to remain alert and take diligent action when they identify a PMD. The authors emphasize the need for counseling because patients may delay diagnosis because of anxiety and denial.