Toluidine blue aids in detection of dysplasia and carcinoma in suspicious oral lesions.

OBJECTIVES: Accurate clinical identification of 'higher-risk' oral premalignant lesions or 'higher-risk' areas within lesions is important. Assessment methods that predict their presence have great utility. SUBJECTS AND METHODS: A cross-sectional, observational study enrolled a consecutive sample of consenting patients diagnosed with oral leukoplakia, erythroleukoplakia, or erythroplakia. Medical history, visual oral examination, ViziLite(®) examination, toluidine blue staining (TBlue(®) ), and finally a biopsy were completed in a single clinic visit. Seventy-seven of 100 examined lesions in 43 patients were biopsied. Sensitivity, specificity, and positive and negative predictive values were computed for visual examination, ViziLite(®) , and TBlue(®) using biopsy results as the gold standard. RESULTS: The sensitivity of TBlue(®) in detecting high-risk lesions (carcinoma in situ or carcinoma) was 94 (71-100, P < 0.0003) and specificity 45 (32-58, P < 0.53), while for carcinoma, sensitivity was 100 (54-100, P < 0.032) and specificity 39 (28-52, P < 0.097). The results of ViziLite(®) testing either by itself or in combination with the information from toluidine blue testing revealed low sensitivity for the detection of high-risk lesions. CONCLUSIONS: Clinical examination of leukoplakia, erythroplakia, or erythroleukoplakia lesions combined with toluidine blue staining may aid in the identification of severe dysplasia (carcinoma in situ) or carcinoma. This may help in determining whether, when, and where (the site within a lesion) a biopsy should be taken.

Use of curcuminoids in a cohort of patients with oral lichen planus, an autoimmune disease.

OBJECTIVES: To summarize long-term open-label use of curcuminoids and experience of side-effects in 53 patients with the autoimmune condition oral lichen planus (OLP) who had previously participated in randomized controlled trials (RCTs) of curcuminoids at UCSF. METHODS: This descriptive retrospective cohort study conducted in 2009 collected information from clinic charts and patient interview on the over-the-counter (OTC) use of curcuminoids during a 1-5 year follow-up period. Of the 53 eligible patients, 33 had previously participated in a RCT (2003-2004) that evaluated a dose of 2000mg/day of curcuminoids and which was ended early for futility and 20 had participated in a RCT (2007-2008) that evaluated a dose of 6000mg/day which demonstrated its efficacy. At the last study visit of each of the 2 RCTs all participants were given current published information about curcuminoids, and some went on to take OTC curcuminoids. RESULTS: Follow-up data was available on 43 participants [25/33 (75%) from the first and 19/20 (95%) from the second RCT]. 18/25 (72%) participants from the first trial took OTC curcuminoids after completion of the trial period. The mean total daily dose was 2137.5mg (SD=793, range 500-3000mg) and mean duration of curcuminoids use was 30 months (SD=27.5). The total follow-up time after completion of the RCT for the 18 participants was mean 68.2 months (SD 5.9). 10/18 (56%) reported that curcuminoids controlled OLP symptoms, and the mean duration of use among these patients was 35.8 months (SD 27.4). 8/18 (44%) were unsure whether curcuminoids helped and the mean duration of use was 21.0 months (SD 27.3). 2 of 18 patients (11%) reported a side-effect (SE) of diarrhea. 19/19 (100%) patients from the second trial took OTC curcuminoids after completion of the trial period. The mean total daily dose was 5058mg (SD=1445, range 1000-6000mg) and mean duration of curcuminoids use 9.6 months (SD=8.04). The total follow-up time after completion of the RCT for the 19 participants was mean 15.8 months (SD 4.8). 12/19 (63%) reported that curcuminoids controlled OLP symptoms, and the mean duration of use was 14.1 months (SD 6.7). 2/19 (11%) reported lack of improvement with a daily dose of 1500mg and 2500mg for 3 months each. 5/19 (26%) were unsure whether curcuminoids helped and the mean duration of use was 1.5 months (1.2 SD). Six of these 19 patients (32%) reported SEs, three had abdominal discomfort, two diarrhea and one slight urgency in defecation on the capsule but not the tablet formulation. The SEs resolved with dose reduction to 4500mg/day in one and 3000mg/day in two patients, while two patients [2/19 (11%)] discontinued curcuminoids due to the SE. CONCLUSIONS: A total of 22/37 (60%) of patients reported a reduction of symptoms with curcuminoids, 13/37 (35%) were unsure and 2/37 (5%) reported that it did not help in reduction of symptoms. Side-effects included abdominal discomfort and diarrhea, however occurrence was dose-related, and complaints were mild.

A randomized, placebo-controlled, double-blind clinical trial of curcuminoids in oral lichen planus.

We studied the efficacy of curcuminoids in the treatment of oral lichen planus (OLP), a chronic, mucocutaneous, immunological disease. Curcuminoids are components of turmeric (Curcuma longa) that have anti-inflammatory activity. Turmeric has been used in Ayurveda (Indian traditional medicine) for centuries. A randomized, double-blind, placebo-controlled trial was conducted. In all, 100 consecutive, eligible patients with OLP presenting to the oral medicine clinic at the University of California, San Francisco, were to be selected. Two interim analyses were to be conducted during the trial. The trial was conducted between February 2003 and September 2004. The first interim analysis was conducted in October 2004 using data from the first 33 subjects. Study subjects were randomized to receive either placebo or curcuminoids at 2000 mg/day for 7 weeks. In addition, all subjects received prednisone at 60 mg/day for the first 1 week. The primary outcome was a change in symptoms from baseline. Secondary outcomes were changes in clinical signs and occurrence of side effects. The first interim analysis did not show a significant difference between the placebo and curcuminoids groups. Conditional power calculations suggested a less than 2% chance that the curcuminoids group would have a significantly better outcome as compared with the placebo group if the trial were continued to completion. Therefore, the study was ended early for futility. Reaching a conclusion regarding the efficacy of curcuminoids based on the results of this study is not possible as it was ended early for futility. Curcuminoids at this dose were well tolerated and the results suggest that for future studies a larger sample size, a higher dose and/or longer duration of curcuminoids administration should be considered; however, for the next step, an RCT of a shorter duration, using a higher dose of curcuminoids, and without an initial course of prednisone, should be considered.

Oral lichen planus: patient profile, disease progression and treatment responses.

BACKGROUND: Oral lichen planus, or OLP, is a common mucocutaneous immunological disease. The objective of this study was to describe the patient profile, disease progression and treatment responses. METHODS: The authors conducted a retrospective, descriptive study using information from patient records at a tertiary referral center. The study included 229 patients with OLP who were seen in the oral medicine clinic at the University of California, San Francisco, between September 1996 and August 2000, for the first time or for a follow-up visit. Signs and symptoms at various clinic visits were quantified. Responses to treatment and disease progression were determined by comparing scores with baseline scores. RESULTS: The mean age at onset of the disease was 55 years, and 154 (67 percent) of the patients were female. Symptoms generally correlated directly with the severity of OLP forms, which ranged from reticular to erosive. Corticosteroids were effective in reducing symptoms, healing ulcers and reducing erythema. At last follow-up, 65 percent of the patients had the same type of OLP seen initially or the disease had progressed to a more severe type, while 35 percent of patients had less-severe forms than that seen at the initial visit. Four patients (1.7 percent) developed oral squamous-cell carcinoma during the follow-up period. CONCLUSIONS: OLP is a chronic disease with no known cure. Symptoms can improve with corticosteroids; however, the lack of long-term (that is, lifetime) treatment compliance and the adverse side effects of the drugs limit optimal results. CLINICAL IMPLICATIONS: Patients with OLP should be treated if symptoms are significant. Follow-up--including supervision of medication use and monitoring of side effects, as well as periodic examinations for possible malignant transformation--is necessary.

Integrin expression in oral hairy leukoplakia and normal tongue epithelium.

OBJECTIVE: To describe the expression of integrins in the epithelium of oral hairy leukoplakia (HL) and compare to that of normal lateral tongue epithelium. MATERIALS AND METHODS: Immunohistochemistry to identify integrins (alpha 2, alpha 3, alpha 5, alpha 6, alpha v, beta 1) was performed, using a standard biotin-streptavidin-peroxidase technique on five clinically and histologically confirmed frozen biopsy specimens of HL and five normal lateral tongue control tissues. RESULTS: Expression of integrins alpha 2, alpha 3, alpha 6, alpha v, beta 1 was seen both in HL epithelium and in normal control tissue. alpha 5 expression was not seen in HL or in control tissue epithelium. alpha 2 and alpha 3 were expressed mainly in the basal and suprabasal layers; alpha 6 expression was most intense on the basal surface of the basal cells, alpha v was expressed in the basal and suprabasal layers with more expression seen in the higher differentiated cell layers than the other integrins. beta 1 expression was seen in the basal and suprabasal layers only. No apparent difference between HL and normal oral mucosa was noted in the staining pattern of the various integrins. CONCLUSION: Integrins alpha 2, alpha 3, alpha 6, alpha v, beta 1 are expressed in HL and the expression pattern is not different from that of normal oral mucosa. alpha 5 is not expressed in HL or in normal oral epithelium.