Faculty Bibliography

BACKGROUND: Dry mouth is a frequent complaint of adults worldwide. In those who experience dry mouth, therapeutic options include the use of salivary substitutes and sialogogues. METHODS: The authors compared the efficacy and safety of mucoadhesive disks (OraMoist, Axiomedic, Zurich; distributed by Quantum Health, Eugene, Ore.) applied three times daily with those of placebo mucoadhesive disks in a double-masked, randomized, controlled crossover study. The primary end point of interest was within-participant differences in subjective (visual analog scale) ratings of dry mouth according to the New York University Bluestone Mouthfeel Questionnaire. The secondary end point was within-participant differences in salivary flow rates. RESULTS: Twenty-seven participants completed the single-site study. The results showed no significant difference between the two types of mucoadhesive disks, both of which were associated with a statistically significant improvement in the subjective experience of moistness across the 60-minute period after application and compared with baseline measures after two weeks of use. Furthermore, both disks were associated with a statistically significant improvement in salivary flow rates across the 60-minute period after application and compared with baseline measures after one and two weeks of use. The disks were well tolerated, and participants did not report any adverse events. CONCLUSIONS: The mucoadhesive disks used in this study were safe and provided symptomatic relief from dry mouth. Practice Implications. Patients with dry mouth may benefit from this novel delivery system.

Endothelin receptor type B (EDNRB) and kinesin family member 1A (KIF1A) are candidate tumor suppressor genes that are inactivated in cancers. In this study, we evaluated the promoter hypermethylation of EDNRB and KIF1A and their potential use for risk classification in prospectively collected salivary rinses from patients with premalignant/malignant oral cavity lesions. Quantitative methylation-specific PCR was performed to analyze the methylation status of EDNRB and KIF1A in salivary rinses of 191 patients. We proceeded to determine the association of methylation status with histologic diagnosis and estimate classification accuracy. On univariate analysis, diagnosis of dysplasia/cancer was associated with age and KIF1A or EDNRB methylation. Methylation of EDNRB highly correlated with that of KIF1A (P < 0.0001). On multivariable modeling, histologic diagnosis was independently associated with EDNRB (P = 0.0003) or KIF1A (P = 0.027) methylation. A subset of patients analyzed (n = 161) without prior biopsy-proven malignancy received clinical risk classification based on examination. On univariate analysis, EDNRB and risk classification were associated with diagnosis of dysplasia/cancer and remained significant on multivariate analysis (EDNRB: P = 0.047, risk classification: P = 0.008). Clinical risk classification identified dysplasia/cancer with a sensitivity of 71% and a specificity of 58%. The sensitivity of clinical risk classification combined with EDNRB methylation improved to 75%. EDNRB methylation in salivary rinses was independently associated with histologic diagnosis of premalignancy and malignancy and may have potential in classifying patients at risk for oral premalignant and malignant lesions in settings without access to a skilled dental practitioner. This may also potentially identify patients with premalignant and malignant lesions that do not meet the criteria for high clinical risk based on skilled dental examination.

Sixty-four standardized continuing education courses were given for dentists throughout the ten public health districts of the USA to determine if certain behaviors regarding oral and pharyngeal cancer (OPC) control could be modified. Questionnaires were obtained at baseline and at 6 months along with matched control groups. One thousand eight hundred two general dentists participated at baseline and 988 at a 6-month questionnaire follow-up. Analysis of the data indicated that continuing education courses had a positive influence on participants' oral cancer attitudes, knowledge, and behavior that potentially could make a difference on prevention, early detection, and ultimately OPC control.

Introduction: Epidemiologic observations have suggested a protective effect of soybeans against a number of epithelial cancers including oral malignancies and by inference precursor lesions such as leukoplakia. Several compounds in soybeans have shown activity in preclinical models; we have focused our studies on BBI (Bowman-Birk inhibitor), which is active against the protease chymotrypsin. Our phase I trial demonstrated a very low toxicity profile and a 31% response rate in a 1-month nonrandomized study that was associated with favorable modulation of protease activity and neu oncogene in exfoliated buccal mucosal cells (EBMC). Methods: An intent-to-treat(ITT) randomized placebo (Quaker mass harina, a corn flour)-controlled, double-blind clinical trial of a soybean concentrate (C) of BBI (600 C.I. units) was performed in a multinstitutional investigation (7 sites). The study duration was 6 months and included pre/interim/postevaluation of lesions sizes and pre/post photographic assessments and oral mucosa biopsies(with post central pathology review) of the involved area(s). Intermediate biomarkers (IBM) included serial measurements of EBMC neu protein (ng/mg) and protease (Delrfu/min/ug protein) and serum neu protein (ng/ml). 325 patients underwent preliminary screening and 148 per protocol eligible were enrolled. Of these, 132 were randomized and 105 completed 6 months on study. All data on lesion sizes, photo judgments, and pathology indications of degree of abnormality or change in abnormality were entered into SAS datasets and subjected to 100% verification against the crf forms by the statistician. The several IBM measurements were converted from the original Microsoft Excel sheets into SAS data sets, and subject to spot checks against the original spreadsheets. Similarly, host-factor information from the questionnaires was spot checked against the original records. In all cases, the primary, per-protocol analyses was ITT. The per-protocol, intent-to-treat cohort, and all other categorizations of study participants will also be described with appropriate descriptive summary measures. Results: The ITT data set is composed of all those with valid, two-dimensional measurements on all lesions observed at both the randomization and 6-month visit. 89 evaluable patients met these criteria: 43 in the treatment and 46 in the placebo group. For the BBIC group, the mean relative percent change in total lesion area was -20.6% and for the placebo group -17.1%. Clinical responses for the 89 patients were: four showed a complete response (4.5%), 22 showed a partial response (25%), 53 showed stable disease (60%), and 10 showed disease progression (11.2%). For the drug group the CR+PR(>50% change) was 27.91% and for placebo group 30.43%. Neither the lesion size nor response comparisons demonstrated differences between the two groups that were significantly different (p>0.05). Photos of the same lesion at baseline and at the 6-month exam were available for 91 participants. Five qualified reviewers made judgments of the degree of change in abnormality on a seven-point scale, blinded to study arm and timepoint of photos. For mean comparison scores, 1 was substantial improvement over time, 4 indicated no change and 7 meaning much worse decline over time. Preliminary assessments of 77% of the patients having pre/post photos indicates that there were no significant differences between the placebo and treatment groups. Conclusion: BBIC is not effective as a chemoprevention agent for the management of oral leukoplakia. Central pathology review by two reviewers is near completion, but is unlikely to affect this conclusion. Final measurements of the three biomarkers should be available by the time of presentation and subanalysis will be presented for the two groups and for the patients who seemed to have had a clinical response

Persistent oral ulcers and erosions can be the final common manifestation, sometimes clinically indistinguishable, of a diverse spectrum of conditions ranging from traumatic lesions, infectious diseases, systemic and local immune-mediated lesions up to neoplasms. The process of making correct diagnosis for persistent oral ulcers still represents a challenge to clinicians. Major diagnostic criteria should include the clinical appearance of both ulcer and surrounding non-ulcerated mucosa, together with the evaluation of associated signs and symptoms, such as: number (single or multiple), shape, severity of the ulcer(s), conditions of remaining mucosa (white, red or with vesiculo-bullous lesions) and systemic involvement (e.g. fever, lymphadenopathy or evaluation of haematological changes). The aim of this paper was to review the literature relating to persistent oral ulcers and provide a helpful, clinical-based diagnostic tool for recognising long-standing ulcers in clinical dental practice. The authors, therefore, suggest distinguishing simple, complex and destroying (S-C-D system) ulcerations, as each requires different diagnostic evaluations and management. This classification has arisen from studying the current English literature relating to this topic, performed using MEDLINE / PubMed / Ovid databases.

BACKGROUND: Adjunctive techniques that may facilitate the early detection of oral premalignant and malignant lesions (OPML) have emerged in the past decades. METHODS: The authors undertook a systematic review of the English-language literature to evaluate the effectiveness of toluidine blue (TB), ViziLite Plus with TBlue (Zila Pharmaceuticals, Phoenix), ViziLite (Zila Pharmaceuticals), Microlux DL (AdDent, Danbury, Conn.), Orascoptic DK (Orascoptic, a Kerr Company, Middleton, Wis.), VELscope (LED Dental, White Rock, British Columbia, Canada) and OralCDx (Oral CDx Laboratories, Suffern, N.Y.) brush biopsy. They abstracted data relating to study design, sampling and characteristics of the study group, interventions, reported outcomes and diagnostic accuracy of adjunctive aids from 23 articles meeting inclusion and exclusion criteria, including availability of histologic outcomes. RESULTS: The largest evidence base was for TB. A limited number of studies was available for ViziLite, ViziLite Plus with TBlue and OralCDx. Studies of VELscope have been conducted primarily to assess the margins of lesions in known OPML. The authors identified no studies of Microlux DL or Orascoptic DK. Study designs had various limitations in applicability to the general practice setting, including use of higher-risk populations and expert examiners. CONCLUSIONS: There is evidence that TB is effective as a diagnostic adjunct for use in high-risk populations and suspicious mucosal lesions. OralCDx is useful in assessment of dysplastic changes in clinically suspicious lesions; however, there are insufficient data meeting the inclusion criteria to assess usefulness in innocuous mucosal lesions. Overall, there is insufficient evidence to support or refute the use of visually based examination adjuncts. Practical Implications. Given the lack of data on the effectiveness of adjunctive cancer detection techniques in general dental practice settings, clinicians must rely on a thorough oral mucosal examination supported by specialty referral and/or tissue biopsy for OPML diagnosis.

A 33-year-old-man presented with a 13-year history of asymptomatic, white, folded, soft, poorly-demarcated, diffuse plaques bilaterally on his buccal mucosae and lateral surfaces of his tongue. There is no family history of similar lesions. The physical examination and histopathologic findings were consistent with a diagnosis of white sponge nevus. This rare disorder is typically inherited; however, as in this case, there have been a few other cases reported without a familial background.