Faculty Bibliography

OBJECTIVES/HYPOTHESIS: To characterize fundamental late tissue effects in the human vocal fold following radiation therapy. To develop a murine model of radiation fibrosis in order to ultimately develop both treatment and prevention paradigms. DESIGN: Translational study using archived human and fresh murine irradiated vocal fold tissue. METHODS: 1) Irradiated vocal fold tissue from patients undergoing laryngectomy for loss of function from radiation fibrosis was identified from pathology archives. Histomorphometry, immunohistochemistry, and whole-genome microarray, as well as real-time transcriptional analyses, were performed. 2) Focused radiation to the head and neck was delivered to mice in a survival fashion. One month following radiation, vocal fold tissue was analyzed with histomorphometry, immunohistochemistry, and real-time PCR transcriptional analysis for selected markers of fibrosis. RESULTS: Human irradiated vocal folds demonstrated increased collagen transcription, with increased deposition and disorganization of collagen in both the thyroarytenoid muscle and the superficial lamina propria. Fibronectin were increased in the superficial lamina propria. Laminin decreased in the thyroarytenoid muscle. Whole genome microarray analysis demonstrated increased transcription of markers for fibrosis, oxidative stress, inflammation, glycosaminoglycan production, and apoptosis. Irradiated murine vocal folds demonstrated increases in collagen and fibronectin transcription and deposition in the lamina propria. Transforming growth factor (TGF)-beta increased in the lamina propria. CONCLUSION: Human irradiated vocal folds demonstrate molecular changes leading to fibrosis that underlie loss of vocal fold pliability occurring in patients following laryngeal irradiation. The irradiated murine tissue demonstrates similar findings, and this mouse model may have utility in creating prevention and treatment strategies for vocal fold radiation fibrosis.

OBJECTIVE/HYPOTHESIS: To determine the efficacy of the potassium titanyl phosphate (KTP) laser in lesion reduction, as well as preservation of mucosal wave and glottic closure in a cohort of patients with benign laryngeal pathology across multiple institutions. STUDY DESIGN: Multi-institutional and retrospective. METHODS: One hundred two patients who underwent in-office KTP procedures at multiple academic laryngology practices with at least a single follow-up visit were included. Image analysis was used to quantify vocal fold lesion size before and after treatment. A subset of images was analyzed by expert reviewers to determine the impact of this treatment on glottic closure and mucosal wave. RESULTS: Statistically, when considering all lesions, KTP induced a significant reduction in lesion size. Post hoc analyses revealed some lesion specificity; all lesions decreased in size, with the exception of vocal fold scar. Mucosal wave and glottic closure were improved or unchanged in more than 90% of the patients examined. The inter- and intrarater reliabilities of the lesion quantification method were excellent. CONCLUSIONS: With great care and insight, the KTP laser appears to be a valuable tool for the treatment of various benign laryngeal lesions. Furthermore, KTP laser therapy appears to preserve or improve mucosal wave and glottic closure. The lesion measurement protocol previously described by our group appears to be reliable.

OBJECTIVES: The recently published Clinical Practice Guideline: Hoarseness (Dysphonia) revealed major deficits in the literature regarding relatively routine clinical decision-making. One of the more controversial points in the Guideline regarded the utility and timing of laryngeal visualization via flexible laryngoscopy, potentially because of sparse literature regarding the risks and potential morbidity. We sought to prospectively address this issue in order to optimize evaluation protocols. METHODS: Two-hundred fifty consecutive patients with a variety of complaints completed a survey after undergoing flexible laryngoscopy. The survey queried 1) demographics; 2) discomfort of pretreatment anesthesia and scope placement in the nose and pharynx; 3) fear of future examinations; and 4) patient perception and past experience. Concurrently, the laryngoscopist reported the complications and anatomic variations encountered. RESULTS: The discomfort and pain ratings from both the anesthetic spray and the scope placement were low. No statistically significant differences were observed with regard to sex; however, women reported greater fear associated with examinations (p = 0.0001). Anatomic abnormalities were observed in 14.4% of patients, and these patients reported greater discomfort, pain, and fear regarding the examination. No adverse events were observed. CONCLUSIONS: Flexible laryngoscopy was well tolerated, with little to no risk. The presence of nasal anatomic abnormalities predicted increased discomfort.

OBJECTIVES/HYPOTHESES: The objective was to assess the utility of selected "resonant voice" (RV) exercises for the reduction of acute vocal fold inflammation. The hypothesis was that relatively large-amplitude, low-impact vocal fold exercises associated with RV would reduce inflammation more than spontaneous speech (SS) and possibly more than voice rest. STUDY DESIGN: The study design was prospective, randomized, and double blind. METHODS: Nine vocally healthy adults underwent a 1-hour vocal loading procedure, followed by randomization to a SS condition, vocal rest condition, or RV exercise condition. Treatments were monitored in clinic for 4 hours and continued extraclinically until the next morning. At baseline (BL), immediately after loading, after the 4-hour in-clinic treatment, and 24 hours post-BL, secretions were suctioned from the vocal folds bilaterally and submitted to enzyme-linked immunosorbent assay to estimate concentrations of key markers of tissue injury and inflammation: interleukin (IL)-1beta, IL-6, IL-8, tumor necrosis factor alpha, matrix metalloproteinase (MMP)-8, and IL-10. RESULTS: Complete data sets were obtained for three markers--IL-1beta, IL-6, and MMP-8--for one subject in each treatment condition. For these markers, results were poorest at 24-hour follow-up in the SS condition, sharply improved in the voice rest condition, and was the best in the RV condition. Average results for all markers and responsive subjects with normal BL mediator concentrations revealed an almost identical pattern. CONCLUSIONS: Some forms of tissue mobilization may be useful to attenuate acute vocal fold inflammation.

BACKGROUND: Dysphagia is a potential consequence of treatment for head and neck cancer. Neuromuscular electrical stimulation (NMES) has evolved as a treatment option, with the goal of improved swallow function in patients with chronic dysphagia. However, the effects of NMES on tumorigenicity are unknown and often confound the initiation of this therapy, potentially limiting its efficacy in treating patients with head and neck cancer. METHODS: Squamous cell carcinoma was grown in the flank of athymic, nude mice. Mice were randomized into treatment and control groups; the experimental group received daily NMES directly to the flank for 8 days. RESULTS: Tumor volumes, recorded on days 0, 3, 7, and 10, demonstrated no significant differences between groups on each day of measurement. Immunohistochemical analysis of apoptosis, proliferation, and vascularization also failed to demonstrate statistically significant differences between treated and untreated groups. CONCLUSIONS: NMES does not promote the growth of underlying tumor in our model. These data may provide preliminary evidence that applying electrical stimulation over the muscles of the anterior neck does not increase the risk of tumorigenicity. Early initiation of NMES in this challenging population may be feasible from an oncologic standpoint. (c) 2011 Wiley Periodicals, Inc. Head Neck, 2011.

OBJECTIVES: The recently published Clinical Practice Guideline raised issues related to the value and timing of laryngoscopy in patients with hoarseness. We sought to determine the extent to which these guidelines concur with clinical practice among members of the American Broncho-Esophagological Association (ABEA). METHODS: A web-based survey was distributed to ABEA members, composed of four sections: 1) background and demographics; 2) information regarding the appropriate length of time that new-onset dysphonia may be managed before laryngeal visualization, given particular comorbidities; 3) the frequency and risks of office-based flexible transnasal laryngoscopy; and 4) the overall value of laryngoscopy and stroboscopy. RESULTS: Seventy-one ABEA members completed the survey; they had a combined 1,468 years of post-residency experience. Approximately 75% of respondents were involved in a fully academic practice. Across all respondents, an average of 11 patients with new voice complaints were seen per week. Overall, 98.6% of respondents believe that laryngoscopy is very valuable. Stridor in a neonate and potential foreign bodies were both conditions necessitating laryngoscopy on the day of presentation. In patients with no serious underlying condition(s), the mean duration until laryngoscopy was 12.96 days (range, 0 to 30 days). CONCLUSIONS: These data suggest that the current practice patterns among experts in the field are divergent from the recently published Guideline.

OBJECTIVE: To investigate the hypothesis that prophylactic triamcinolone modulates acute vocal fold inflammatory and profibrotic signaling during acute phonotrauma. STUDY DESIGN: In vivo rabbit phonation model. SETTING: Academic medical center. SUBJECTS AND METHODS: Forty New Zealand white breeder rabbits were randomly assigned to 1 of 4 groups: control (no intervention), no treatment (30 minutes of raised intensity phonation), sham treatment (bilateral intralaryngeal triamcinolone acetonide injection at 0 microg/25 microL followed by 30 minutes of raised intensity phonation), or steroid treatment (bilateral intralaryngeal triamcinolone acetonide injection at 400 microg/25 microL followed by 30 minutes of raised intensity phonation). Quantitative polymerase chain reaction (qPCR) was used to investigate gene expression levels of cyclooxygenase-2 (COX-2), interleukin (IL)-1beta, and transforming growth factor (TGF)-beta1. RESULTS: Results revealed a significant main effect for COX-2 (P = .002). Post hoc testing revealed that rabbits receiving no treatment (15.10) had higher COX-2 gene expression than control (5.90; P < .001). There were no significant differences in COX-2 expression between treatment groups. Results revealed a significant main effect for IL-1beta (P < .001). Post hoc testing revealed that rabbits receiving no treatment (14.70) had higher IL-1beta gene expression than control (6.30) (P = .001). There were no significant differences in IL-1beta gene expression between treatment groups. There were no significant differences in TGF-beta1 gene expression (P = .525) between treatment and control groups. CONCLUSION: Given conflicting evidence, further studies are necessary to investigate vocal fold steroid injections prior to and following the induction of phonotrauma. Prophylactic administration of triamcinolone immediately prior to acute phonotrauma resulted in no significant changes in COX-2, IL-1beta, and TGF-beta1 gene transcript levels.

Objective: Glucocorticoids are commonly used treatments in otolaryngology, but guidelines about their use are vague and irregular. We sought to assess clinical practices with regard to glucocorticoid use for patients with laryngeal disease and to ascertain factors driving clinician drug choice. Method: A web-based survey was distributed to otolaryngologists via email using the Ear, Nose, and Throat (ENT) Journal database. This survey was composed of 20 questions and collected the following data from respondents: 1) indications for the use of glucocorticoids in their practice, 2) decision-making process influencing the choice of glucocorticoid, 3) background and demographics. Results: Two hundred eight otolaryngologists completed the survey, with 99% (n = 196) reporting that glucocorticoids were valuable to their practice. "Previous experience/results," "familiarity," and "use in practice" (n = 144, 114, and 79, respectively) were commonly cited reasons for choosing a particular glucocorticoid, whereas pharmacokinetic profile and "academic literature" were infrequently cited concerns. Only 54.4% (n = 106) of respondents said that they were more likely to prescribe glucocorticoids for vocal performers as compared to other patients. Additionally, most respondents said side effects only "occasionally" prevented them from prescribing glucocorticoids to patients. Conclusion: These results suggest that glucocorticoid prescription practices vary greatly between otolaryngologists, and drug choice is driven primarily by clinician preference rather than more objective factors. These findings indicate a need for further research about this powerful class of drugs, and the importance of establishing clear, appropriate guidelines regarding their use.

OBJECTIVES/HYPOTHESIS: In this article we describe a methodology for obtaining high-quality dynamic magnetic resonance imaging (MRI) sequences of the swallow sequence in healthy volunteers. The study includes comparison to previous work done in our lab using a 1.5 Tesla (T) magnet. STUDY DESIGN: Case series. METHODS: Three healthy volunteers underwent turbo-fast low angle shot MRI at 3T while swallowing liquid boluses delivered via intravenous tubing to the oral cavity. Imaging was performed in the sagittal and axial planes. RESULTS: Imaging provided by this sequence provided high temporal resolution, with the ability to depict deglutition in the axial and sagittal planes. Comparison with imaging at 1.5T demonstrated benefits in temporal resolution and signal-to-noise. Anatomic information provided differed from comparative videofluoroscopy. CONCLUSIONS: MRI of swallowing using the described technique is reliable and provides a unique evaluation of the swallowing sequence. Laryngoscope, 2012.

OBJECTIVES: We sought to better characterize pathologic changes that occur in the human vocal fold after radiotherapy for head and neck cancer. METHODS: In a blinded, controlled study of archived tissue, we evaluated postirradiation salvage laryngectomy vocal fold tissue without evidence of malignant disease. Clinical and demographic patient data were collected. In a blinded fashion, irradiated tissue was compared to nonirradiated, benign control tissue. Histomorphometric analysis was used to assess muscle and collagen organization, superficial lamina propria (SLP) and vocal ligament thickness, vocalis muscle fiber area, collagen content, and hyaluronic acid content. Immunohistochemical analysis was used to assess the content of type I collagen, type IV collagen, vimentin, fibronectin, alpha-smooth muscle actin, matrix metalloproteinase 9, and laminin. RESULTS: Twenty irradiated vocal folds were evaluated and compared to control specimens. Collagen and muscle disorganization was noted in the irradiated specimens. The SLP and vocal ligament thicknesses and the mean muscle fiber diameters did not differ significantly. The SLP fibronectin and the vocalis muscle and SLP collagen content were significantly increased in the irradiated vocal folds, and the SLP collagen content increased significantly with time between irradiation and resection. The laminin content of irradiated vocalis muscles was significantly decreased. CONCLUSIONS: Radiotherapy results in significant vocal fold tissue changes. Having more precisely defined these changes, we plan continued investigation seeking targeted preventive and therapeutic interventions for improved vocal quality following radiotherapy.