Dental Caries Postradiotherapy in Head and Neck Cancer.

BACKGROUND: Treatment for head and neck cancer (HNC) such as radiotherapy (RT) can lead to numerous acute and chronic head and neck sequelae, including dental caries. The goal of the present study was to measure 2-y changes in dental caries after radiotherapy in patients with HNC and test risk factors for caries increment. METHODS: Cancer and dental disease characteristics, demographics, and oral health practices were documented before and 6, 12, 18, and 24 mo after the start of RT for 572 adult patients with HNC. Patients were eligible if they were age 18 y or older, diagnosed with HNC, and planned to receive RT for treatment of HNC. Caries prevalence was measured as decayed, missing, and filled surfaces (DMFS). The association between change in DMFS and risk factors was evaluated using linear mixed models. RESULTS: On average, DMFS increased from baseline to each follow-up visit: 6 mo, +1.11; 12 mo, +2.47; 18 mo, +3.43; and 24 mo, +4.29 (P < 0.0001). The increase in DMFS during follow-up was significantly smaller for the following patient characteristics: compliant with daily fluoride use (P = 0.0004) and daily oral hygiene (brushing twice daily and flossing daily; P = 0.015), dental insurance (P = 0.004), and greater than high school education (P = 0.001). DMFS change was not significantly associated with average or maximum RT dose to the parotids (P > 0.6) or salivary flow (P > 0.1). In the subset of patients who had salivary hypofunction at baseline (n = 164), lower salivary flow at follow-up visits was associated with increased DMFS. CONCLUSION: Increased caries is a complication soon after RT in HNC. Fluoride, oral hygiene, dental insurance, and education level had the strongest association with caries increment after radiotherapy to the head and neck region. Thus, intensive oral hygiene measures, including fluoride and greater accessibility of dental care, may contribute to reducing the caries burden after RT in HNC. KNOWLEDGE TRANSFER STATEMENT: The results of this study can be used by clinicians when deciding how to minimize oral complications related to cancer therapy for patients with head and neck cancer. Identification of modifiable factors (e.g., oral hygiene and prescription fluoride compliance) associated with increased caries risk can minimize radiation caries burden.

Immunohistopathological characterization and the impact of topical immunomodulatory therapy in oral chronic graft-versus-host disease: A pilot study.

OBJECTIVE: To characterize the immunohistopathological features of oral chronic graft-versus-host disease (cGVHD), and the impact of topical immunomodulatory therapy on the infiltrating cells. MATERIAL AND METHODS: Paired oral cGVHD biopsies obtained before (n = 12) and 1 month after treatment (n = 12) with topical dexamethasone (n = 8) or tacrolimus (n = 4) were characterized by immunohistochemistry using a panel of CD1a, CD3, CD4, CD8, CD20, CD31, CD62E, CD103, CD163, c-kit, and FoxP3. Controls included acute GVHD (aGVHD; n = 3), oral lichen planus (OLP; n = 5), and normal tissues (n = 5). RESULTS: Oral cGVHD specimens prior to treatment were mainly characterized by basal cell squamatization, lichenoid inflammation, sclerosis, apoptosis, and lymphocytic exocytosis. The infiltrating cells in oral cGVHD primarily consisted of CD3+ , CD4+ , CD8+ , CD103+ , CD163+ , and FoxP3+ cells, which were higher than in normal tissues. Topical dexamethasone or tacrolimus reduced neutrophilic exocytosis, basal cell squamatization, and lichenoid inflammation in oral cGVHD, and dexamethasone reduced the number of CD4+ and CD103+ cells. CONCLUSION: The high expression of CD3, CD4, CD8, CD103, CD163, and FoxP3 confirms that oral cGVHD is largely T-cell-driven with macrophage participation. The impact of topical immunomodulatory therapy was variable, reducing histological inflammatory features, but with a weak clinicopathological correlation. Topical dexamethasone reduced the expression of CD4 and CD103, which may offer novel therapeutic targets.

Oral mucous membrane pemphigoid and pemphigus vulgaris-a retrospective two-center cohort study.

OBJECTIVES: Few studies have compared oral mucous membrane pemphigoid (MMP) and pemphigus vulgaris (PV). Descriptive analysis of oral features, extent of extra-oral involvement, and management outcomes were performed. SUBJECTS AND METHODS: Patients with PV and MMP, the latter with exclusive oral involvement at first presentation, were included. RESULTS: There were 26 MMP (46%) and 31 PV (54%) patients. Desquamative gingivitis was evident in 84% of MMP cases compared to 28% of PV cases (P < 0.05). Non-gingival lesions were noted in 6% of MMP cases compared to 55% of PV cases (P < 0.01). Management of MMP consisted of only topical corticosteroids in 88% of cases while 12% of cases required concomitant systemic therapy. All PV cases (100%) required systemic therapy. No patients with MMP developed scarring or ocular lesions, and one patient (4%) developed cutaneous lesions. Five PV cases (16%) had oral cavity involvement only with three (60%) developing pharyngeal involvement and two (40%) developing cutaneous lesions on follow-up. CONCLUSION: Oral MMP presents primarily as desquamative gingivitis, infrequently involving extragingival sites, and is highly amenable to topical therapy, while PV is a systemic mucocutaneous disease with extensive non-gingival oral lesions that almost always requires systemic therapy.

Oral chronic GVHD outcomes and resource utilization: a subanalysis from the chronic GVHD consortium.

OBJECTIVES: This study evaluated the extent to which oral chronic graft-versus-host disease (cGVHD) consensus assessments are predictive of management across institutions with and without oral medicine (OM) centers, and whether ancillary care guidelines are followed within clinical practice. METHODS: Longitudinal oral cGVHD data were abstracted from the cGVHD Consortium, and additional mouth-specific management data were analyzed across five transplant centers. RESULTS: Seventy-nine patients with 656 visits were observed for a median of 7.1 months with one visit per follow-up month. Ancillary therapies for oral cGVHD were prescribed for 67% of patients for a median of 0.46 months (per follow-up month) at OM centers and 0.78 months at non-OM centers. Patients treated with ancillary therapy were more likely to have an National Institutes of Health (NIH) mouth score of ≥1 (P < 0.001, odds ratio: 5.1) and mouth pain (P = 0.01, odds ratio: 2.6). The odds ratios of receiving ancillary therapy from OM experts were higher than transplant physicians (53%; P = 0.03). CONCLUSIONS: Oral cGVHD consensus assessments corresponding with ancillary therapy use were mouth pain and NIH mouth score, with higher odds ratios of receiving therapy from OM experts. Ancillary care guidelines for oral cGVHD are reflected in academic clinical practice with respect to utilization of recommended prescriptions.

Initial experience of dual maintenance immunosuppression with steroid withdrawal in vascular composite tissue allotransplantation.

Current immunosuppression in VCA is largely based on the experience in solid organ transplantation. It remains unclear if steroids can be reduced safely in VCA recipients. We report on five VCA recipients who were weaned off maintenance steroids after a median of 2 months (mean: 4.8 months, range 2-12 months). Patients were kept subsequently on a low dose, dual maintenance consisting of tacrolimus and mycophenolate mofetil/mycophenloic acid with a mean follow-up of 43.6 months (median = 40 months, range 34-64 months). Early and late acute rejections responded well to temporarily augmented maintenance, topical immunosuppression, and/or steroid bolus treatment. One late steroid-resistant acute rejection required treatment with thymoglobulin. All patients have been gradually weaned off steroids subsequent to the treatment of acute rejections. Low levels of tacrolimus (<5 ng/mL) appeared as a risk for acute rejections. Although further experience and a cautious approach are warranted, dual-steroid free maintenance immunosuppression appears feasible in a series of five VCA recipients.

Resource utilization in cancer patients with bisphosphonate-associated osteonecrosis of the jaw.

BACKGROUND AND OBJECTIVE: Bisphosphonate-associated osteonecrosis of the jaw (BONJ) is an emerging oral complication that occurs most commonly in the setting of high-dose bisphosphonate therapy for cancer. The purpose of this study was to estimate the health care-related costs associated with a diagnosis of BONJ in patients with cancer evaluated and managed at one tertiary oral medicine practice. METHODS: This was a retrospective electronic medical record review of cancer patients with BONJ. All health care-related resources were abstracted using a structured chart abstraction tool; data captured included medications, imaging studies, laboratory investigations, procedures, and visits. Standardized references were used to assign costs in 2010 US dollars. RESULTS: Ninety-two cancer patients with BONJ were identified who were followed for a median of 12 months. The median cost of a case of BONJ was $1667 (interquartile range from $976 to $3350). Medication costs comprised the majority (42%) of the total costs, followed by procedural interventions (22%), clinic visits (19.5%), and imaging studies (13.8%). Patient factors associated with higher median costs included a greater number of involved oral quadrants and more advanced BONJ stage. CONCLUSION: There are considerable costs associated with the diagnosis and management of BONJ in patients with cancer, with medications accounting for nearly half of resource expenditures.

Placebo effect in burning mouth syndrome: a systematic review.

Placebo controls play a critical role in the evaluation of any pharmacotherapy. This review surveys the placebo arm in 12 randomized controlled trials (RCTs) investigating burning mouth syndrome (BMS) and documents a positive placebo response in 6 of them. On average, treatment with placebos produced a response that was 72% as large as the response to active drugs. The lack of homogeneity in the use of placebos adds to the difficulty in comparing results and aggregating data. Future RCTs investigating BMS would benefit from larger sample sizes, adequate follow-up periods, and use of a standard placebo.

Influence of androgens on gene expression in the BALB/c mouse submandibular gland.

Androgens have profound effects on the murine submandibular gland. Our objective was to determine the nature and extent of androgen control of gene expression in the submandibular gland, and to explore the degree to which this might account for known sex differences. Orchiectomized male BALB/c mice were treated with placebo- or testosterone-containing hormone pellets for 14 days. Glands were collected, and total RNA was isolated. Samples were analyzed for differentially expressed mRNAs by CodeLink microarrays, and the data were evaluated with GeneSifter. Androgens significantly (p < 0.05) influenced the expression of over 1300 genes, and many (n = 366) of the genes differentially regulated by androgen treatment were also differentially expressed in males compared with the females in our previous study. These findings support our hypotheses that testosterone extensively influences gene expression in the male submandibular gland, and that many of the sex differences are due to androgens.

Sex-related differences in gene expression in salivary glands of BALB/c mice.

Sex-related differences exist in the structure and function of the major glands in a variety of species. Moreover, many of these variations appear to be unique to each tissue. We hypothesized that this sexual dimorphism is due, at least in part, to gland-specific differences in gene expression between males and females. Glands were collected from male and female BALB/c mice (n = 5/sex/experiment), and total RNA was isolated. Samples were analyzed for differentially expressed mRNAs with CodeLink microarrays, and data were evaluated by GeneSifter. Our results demonstrate that significant (P < 0.05) sex-related differences exist in the expression of numerous genes in the major salivary glands, and many of these differences were tissue-specific. These findings support our hypothesis that sex-related differences in the salivary glands are due, at least in part, to tissue-specific variations in gene expression.