Faculty Bibliography

BACKGROUND: We recently identified MUC1 as a target driving selection for 1q21 amplification and validated it as an independent marker of aggressive behavior in thyroid cancer (TC). The aims of this study were to determine whether TC cell lines retain MUC1 expression patterns that are seen in primary tumors, assess the role of MUC1 in tumor maintenance, and develop a virally delivered anti-MUC1 RNA interference (RNAi) that is effective in decreasing MUC1 expression in vitro. METHODS: Fifteen TC cell lines were screened for MUC1 protein expression. Cell lines with varying MUC1 protein levels were treated with anti-MUC1 monoclonal antibody to assess cell viability. A recombinant retroviral short hairpin RNAi delivery system against MUC1 was developed. Efficacy and optimal dosing of short hairpin RNA against MUC1 was determined. RESULTS: MUC1 expression patterns in TC cell lines were found to be similar to that seen in primary tumors. Treatment with anti-MUC1 antibody resulted in a significant decrease in cell viability in MUC1 over-expressing cell lines. MUC1-779 RNAi construct showed excellent infection efficiency and reproducible silencing. CONCLUSION: These data offer functional evidence that implicates MUC1 over-expression as a key molecular event in the pathogenesis of aggressive TC. Retrovirally delivered anti-MUC1 RNAi is effective in silencing MUC1 and merits further investigation to establish therapeutic efficacy and safety in anticipation of potential clinical application

OBJECTIVES: This article presents the first report of cochlear implantation in a patient with congenital aural atresia, microtia, dysplastic cochlea and internal auditory canals, and bilateral profound sensorineural hearing loss (HL). This rare combination requires special management considerations. Preoperative issues include thorough evaluation of computed tomography and magnetic resonance imaging to determine favorable anatomy, cochlear implantation candidacy, and surgical planning. Intraoperative concerns include incision placement, surgical approach to the middle ear, and abnormal facial nerve anatomy. Postoperative use of a special headset combining a microphone and transmitter coil is required. STUDY DESIGN: Case report and literature review. METHODS: The patient's chart was reviewed for diagnostic studies, operative strategy, and postoperative auditory stimulation and testing. A literature review was performed. RESULTS: A 2-year-old male presented with bilateral aural atresia, microtia, and profound sensorineural HL. Imaging studies revealed multiple abnormalities of the cochlea, vestibule, and internal auditory canal, all of which were more favorable on the right side. An incision was designed to accommodate future microtia repair. The cochlear implant was placed without difficulty by way of a facial recess approach to the middle ear. Postoperative results include the detection of Ling sounds and voices in the environment as well as the ability to locate sounds. CONCLUSIONS: This is the first report of cochlear implantation in a patient with bilateral aural atresia, microtia, and profound sensorineural HL in conjunction with multiple inner ear abnormalities. Close collaboration among the otologist, neuroradiologist, and plastic surgeon is essential to coordinate surgical management and optimize cosmetic and functional outcomes in this unique population

OBJECTIVE: The purpose of this study was to compare the rate of malignancy in thyroid nodules discovered incidentally on magnetic resonance imaging, computed tomography, and sonography with the rate of malignancy in nonincidentally discovered nodules. METHODS: All thyroid sonographic and fine-needle aspiration (FNA) procedures performed during a 6-month period were retrospectively reviewed. Study indications were categorized as incidental (thyroid nodules found on magnetic resonance imaging, computed tomography, or sonography performed for nonthyroid indications) or nonincidental (studies prompted by abnormal physical examination findings or laboratory values or signs or symptoms suggestive of thyroid disease). Rates of malignancy in patients with incidentally discovered nodules were compared with rates in patients with nonincidental thyroid abnormalities by the Fisher exact test. RESULTS: Of 225 thyroid sonographic studies, 35 (16%) were performed for incidentally discovered thyroid nodules, and 190 (84%) were performed for evaluation of nonincidental thyroid abnormalities. A total of 21 patients (60%) in the incidental group and 90 patients (47%) in the nonincidental group underwent FNA. The rate of malignancy in nodules examined by biopsy in the incidental group was 17% compared with 3% in the nonincidental group (P = .020). Patient sex, multiplicity of nodules, nodule size, echo texture, and presence of calcifications did not differ significantly between the groups. The mean age of patients in the incidental group was significantly higher (61 versus 51 years; P = .007); however, advanced age was not associated with a greater rate of malignancy. CONCLUSIONS: This study identified an unexpectedly high rate of malignancy in incidentally discovered thyroid nodules, suggesting that incidentally discovered thyroid nodules should be evaluated with follow-up thyroid sonography and FNA

We examined measures of oral and pharyngeal residues from scintigraphic studies and estimates/observations from videofluorographic (modified barium swallow) studies taken on the same day but not concurrently in 16 dysphagic patients of varying etiologies presenting with oral and/or pharyngeal dysphagia. Oral and pharyngeal residuals following the swallow were quantified scintigraphically and were then compared with measures of residuals obtained from the modified barium swallow. Estimates of oral and pharyngeal residues from the modified barium swallows were generated by a trained observer who was blinded to the scintigraphic data. Positive and significant Spearman correlations between oral and pharyngeal residue measures from scintigraphy and observations of oral and pharyngeal residues from modified barium swallows were found. This supports the validity of observations of oral and pharyngeal residues in clinical studies. Limitations of these observations are discussed

OBJECTIVE: To evaluate quality of life issues in patients with laryngeal cancer after treatment with either chemoradiation or total laryngectomy and radiation therapy. METHODS: Forty-nine patients with a history of stage II-IV laryngeal squamous cell carcinoma treated primarily with either chemoradiation or by total laryngectomy with postoperative radiation completed the University of Washington Quality of Life instrument, version 4. Patients were identified on a volunteer basis in an academic university head and neck clinic setting. Each patient completed the above instrument, and statistical analysis was performed by Wilcoxon and chi 2 tests. RESULTS: Instruments were completed by all 49 patients: 15 patients who underwent primary chemoradiation and 34 patients who underwent a total laryngectomy followed by radiation. Domains reported in both treatment groups without significant differences were appearance, activity, recreation, moods, taste, saliva, anxiety, and general questions. However, there were significant differences between the 2 groups in the domains of pain, swallowing, chewing, speech, and shoulder function. The laryngectomy patients reported greater impairment of speech (P = 0.001), and shoulder function (P = 0.018), whereas the chemoradiation patients suffered from greater pain, difficulty swallowing (P = 0.061), and problems chewing (P = 0.027). CONCLUSIONS: Most patients with laryngeal cancer, whether treated primarily with chemoradiation or total laryngectomy, reported excellent functional outcomes and health-related quality of life. Pain, swallowing, chewing, saliva, and shoulder function were recorded as significant factors affecting their daily quality of life

Cochlear implants are electrical prostheses that partially replace the functions of the human ear. They bypass normal hearing operation to directly simulate the auditory nerve with electric current. The input acoustic signal passes through a filter bank and the output of each filter modulates the energy of a stimulation waveform delivered to a different intra-cochlear electrode. This approach attempts to mimic the signal processing that takes place in a normal ear. When fitting a cochlear implant to a patient who has lost his hearing after learning language, one important problem is how to optimize the frequency range of the filter bank This optimization seeks a tradeoff between maximum speech perception and the patient\\\\\\\'s subjective preference. Unfortunately, currently available tools to change the frequency-to-electrode mapping (i.e., the frequencies of the filter bank) are cumbersome to use. In a previous project we developed a real time speech processor for the Nucleus-22 and Nucleus-24 cochlear implants, based on a common PC and additional hardware drivers. The present project involves the development of a similar system that is adjustable in real time. In other words, the patient can modify the frequency-to-electrode map using computer keystrokes, and a visual representation of the frequency range employed by the filter bank is displayed on the monitor. The patient adjusts the frequency range interactively and selects the preferred setting in a much faster way than can be accomplished with commercially available hardware. If successful, this approach may be implemented in the next generation of hardware used to program cochlear implants in the clinic

OBJECTIVES/HYPOTHESIS: The objective was to determine whether there is an increased incidence of otorrhea in young children with tympanostomy tubes who swim and bathe without water precautions as compared with children who use water precautions in the form of ear plugs. STUDY DESIGN: Prospective, randomized, investigator-blinded, controlled trial. METHODS: Two hundred one children (age range, 6 mo-6 y) who had undergone bilateral myringotomy and tube insertion were randomly assigned into one of two groups: swimming and bathing with or without ear plugs. Children were seen monthly for 1 year and whenever there was intercurrent otorrhea. RESULTS: Ninety children with and 82 children without ear plugs returned for at least one follow-up visit. Mean (SD) duration of follow-up was 9.4 (4.1) months for the children with ear plugs and 9.1 (4.4) months for the children without ear plugs. Forty-two children (47%) who wore ear plugs developed at least one episode of otorrhea, as compared with 46 (56%) who did not use ear plugs (logistic regression adjusting for stratification variables, P = .21). The mean (SD) rate of otorrhea per month was 0.07 (0.31) for the children who wore ear plugs as compared with 0.10 (0.31) for the children who did not wear ear plugs (Poisson regression adjusting for stratification variables, P = .05). CONCLUSION: There is a small but statistically significant increase in the rate of otorrhea in young children who swim and bathe without the use of ear plugs as compared with children who use ear plugs. Because the clinical impact of using ear plugs is small, their routine use may be unnecessary

OBJECTIVE: To assess behavior and quality of life in children with obstructive sleep apnea (OSA) undergoing tonsillectomy and adenoidectomy compared with control children. DESIGN: Prospective controlled study. SETTING: Hospital-based pediatric otolaryngology practice. PARTICIPANTS: Forty-two children (25 boys and 17 girls; mean [SD] age, 5.8 [2.5] years) with OSA confirmed by positive findings on polysomnography undergoing tonsillectomy and adenoidectomy and 41 control children (29 boys and 12 girls; mean [SD] age, 7.3 [3.8] years) with no history of snoring undergoing unrelated elective surgery. INTERVENTIONS: Parents completed the standardized Child Behavior Checklist and a validated pediatric OSA quality-of-life survey before and 3 months after surgery. MAIN OUTCOME MEASURES: Child Behavior Checklist T scores and score classifications and quality-of-life survey mean scores. RESULTS: Change in mean total problem T score was significantly greater in the OSA group (from 51.6 at baseline to 48.3 at follow-up) than in controls (from 45.5 at baseline to 46.7 at follow-up) (P = .03). The improvement in total T score classification (normal vs borderline or abnormal) was significant for children with OSA compared with control children (P = .009). Children with OSA had significant improvements in the quality-of-life survey mean total score and all individual domain scores compared with controls (P<.001). CONCLUSIONS: Behavioral and emotional difficulties are found in children with documented OSA compared with control children, and they improve after treatment. Large improvements in disease-specific quality of life are also found. Scores on a standardized measure of behavior assessment demonstrated significant correlation with scores on a validated quality-of-life instrument

Beta-6 Integrin, tenascin-C, and MMP-1 (matrix metalloproteinase-1) are invasion-related proteins that are frequently overexpressed in many human malignancies. The objective of this study was to determine whether there is overexpression of these molecules in three types of salivary neoplasms showing markedly different behavior. A total of 55 formalin-fixed, paraffin-embedded archived specimens comprising 19 adenoid cystic carcinomas (ACC), 18 polymorphous low-grade adenocarcinomas (PLGA) and 18 pleomorphic adenomas (PA) were utilized in this study. A standard immunohistochemical technique was used to determine the expression levels of beta-6 integrin, tenascin-C, and matrix metalloproteinase-1 (MMP-1) proteins. Sections were assessed semiquantitatively, and tumors were divided into two groups, low-expressors (0-1+) and high-expressors (2-3+) for statistical analysis. Staining was graded as 0 (<1% positive tumor cells), 1+ (<25% positive tumor cells), 2+ (25-50% positive tumor cells), and 3+ (>50% positive cells). The results showed that the malignant tumors were higher expressors of beta-6 than the benign tumors. ACCs showed significantly higher expression of beta-6 than PAs (p=0.04). No significant difference was observed between ACCs and PLGAs. beta-6 expression was rarely seen in normal salivary gland epithelium and was occasionally present in mucosa overlying the tumors. PAs were high-expressors of tenascin-C with a significant difference relative to ACCs (p=0.03). A majority of tumors in all three tumor types showed high expression of MMP1 with expression significantly greater in the PAs compared to ACCs (p=0.008). We conclude that ACCs and PLGAs express beta-6, tenascin-C, and MMP-1, but that their expression patterns are not significantly different. beta-6 appears to be more closely associated with the malignant tumors, and MMP-1 more closely associated with the benign tumors. We believe that beta-6, tenascin-C, and MMP-1 proteins are part of the molecular repertoire used by salivary tumors for malignant invasion and benign tumor expansion