Faculty Bibliography

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/HYPOTHESIS: No studies to date have examined the clinical safety and efficacy of carboxymethylcellulose (CMC) for vocal fold injection. The current study investigates the voice outcomes and complications of CMC injection. STUDY DESIGN: Retrospective review. METHODS: All patients who underwent CMC injection from three independent sites in a 1-year period were reviewed. Voice outcomes in the form of voice handicap index-10 (VHI-10) and complications from injection were recorded. RESULTS: Seventy-eight patients with VHI-10 results from 1 to 8 weeks after CMC injection were evaluated. Thirty-eight patients were treated for vocal fold immobility, and 15 patients underwent treatment for hypomobility, 15 for vocal fold atrophy, seven for scar/sulcus, one for previous laryngeal fracture, one for functional dysphonia, and one for persistent granuloma. In 60 patients with available VHI-10 data, overall improvement in voice was seen. There was a mean decrease in VHI-10 of 7.48 (26.4 to 18.9, P < .05), correlating to a 19.9% decrease. Forty-five patients (75%) showed a decrease in VHI-10, nine (15%) showed an increase, and six (10%) showed no change. Statistically significant differences were seen for patients with immobility (decrease of 8.6, or 31%) and hypomobility (decrease of 10.7, or 37.8%). There were no complications of vocal fold stiffness, inflammatory reaction, or scar in the 78 patients during the total follow-up period. CONCLUSIONS: CMC is a viable, safe, and efficacious material for the temporary treatment of glottic insufficiency in vocal fold immobility and hypomobility, with minimal risk of permanent adverse voice outcomes.

OBJECTIVES/HYPOTHESIS: Given the recent emergence of encouraging efficacy data regarding the utility of intralesional glucocorticoid (GC) injection for a variety of vocal fold pathologies, we sought to describe the location and expression pattern of the GC receptors within the vocal folds and quantify the effects of GCs on vocal fold fibroblasts. STUDY DESIGN: In vitro, in vivo. METHODS: Immunolocalization of the GC receptor was performed on normal rat vocal fold tissue. Receptor expression was also assayed in our human vocal fold fibroblast cell line. These cells were then treated with exogenous dexamethasone (DM) to quantify the effects of GCs on receptor expression, proliferation, transforming growth factor (TGF)-beta-induced collagen secretion, and matrix protease synthesis. RESULTS: Positive immunostaining for the GC receptor was found throughout the vocal fold with particularly strong staining in the epithelium and capillaries. Human vocal fold fibroblasts constitutively express the GC receptor, but this expression decreased in response to exogenous DM. DM also decreased fibroblast proliferation and TGF-beta-induced collagen synthesis. DM also abrogated TGF-beta-mediated effects on enzymes related extracellular matrix turnover. CONCLUSIONS: Our data are the first to provide mechanistic insight regarding the recently published favorable data regarding the utility of GCs in patients with vocal fold scar. Although further investigation is warranted, both the accessibility of this class of agents and the amenability to office-based procedures are likely to direct patient care models

OBJECTIVES/HYPOTHESIS.: Prostaglandin (PG)E(2) has been implicated in a variety of disease processes. It has been described as antifibrotic in the lower airway, yet scar-inducing in the skin. We seek to describe the effects of PGE(2) on vocal fold fibroblasts and its interactions with transforming growth factor (TGF)-beta1. In addition, we describe a novel organotypic model, a critical step in the development of therapeutic trials. STUDY DESIGN.: In vitro, ex vivo. METHODS: Collagen secretion by human vocal fold fibroblasts (HVFF) was assayed in response to TGF-beta1, PGE(2) , and specific EP receptor agonists. Basal HVFF migratory rate was also quantified in response to PGE(2) . TGF-beta1 induced COX-2 mRNA expression/PGE(2) secretion was assayed. Excised vocal folds were subjected to exogenous IL-1beta; PGE(2) secretion into the supernatant was then assayed. RESULTS: TGF-beta1-induced collagen secretion was blunted in a dose-dependent manner in response to PGE(2) . This effect appears to be mediated primarily through the EP1 and EP2 receptors. TGF-beta1 induced COX-2 mRNA expression and PGE(2) secretion. In our organ culture model, IL-1beta stimulated PGE(2) secretion in a dose-dependent manner. CONCLUSIONS: PGE(2) is antifibrotic; this finding suggests that the upper airway response to this inflammatory mediator differs significantly from the lower airway. These data have important clinical implications for a variety of pathological processes. Furthermore, exogenous TGF-beta1 elicits induction of COX-2, suggesting inherent complexity regarding these processes and PGE(2) signaling, specifically. In addition, our organ culture model may prove useful as a means to quantify biological phenomena in the vocal folds

OBJECTIVES/HYPOTHESIS: Idiopathic ulcerative laryngitis (IUL) is a distinct, clinical entity that presents after a prolonged upper respiratory infection with cough. It is characterized by the development of bilateral ulcerations of the mid-membranous vocal folds followed by a protracted course of healing. The purpose of this review was to characterize the typical patient presentation, clinical findings, and prognosis. STUDY DESIGN: Multi-institutional retrospective review METHODS: Retrospective review of charts and videostroboscopic exams from patients with IUL at eight institutions. RESULTS: Fifteen cases met the criteria for IUL and were included in the study. The mean age of the patients was 49 years, and 93% were female. All patients were nonsmokers. Multiple medical interventions were employed by the treating otolaryngologist during the course of the disease, none of which resulted in acute resolution of the ulcerations. The average time from initial presentation to resolution of the disease was 3.3 months. All of the patients reported that their voice was improved after resolution of the disease process. However, in the majority of the patients (60%) there were persistent vibratory abnormalities after resolution of the ulcerations. CONCLUSIONS: This is the first multi-institutional study to define the complete disease course of IUL and to establish diagnostic criteria. IUL is a rare yet well-recognized clinical entity; however, there is no established etiology for this condition and no definitive treatments have emerged. Further study is needed to establish the etiology/risk factors of this condition and to determine optimal medical management

OBJECTIVES/HYPOTHESIS: Although the potassium titanyl phosphate (KTP) laser is versatile, the variability in laser parameters for laryngeal pathologies and the lack of clinical efficacy data remain problematic. We provide preliminary data regarding these parameters for benign lesion regression. In addition, we describe a novel method for the quantification of the effects of the KTP laser on vocal fold (VF) lesions. STUDY DESIGN: Retrospective chart review. METHODS: Images were captured from examinations before and after in-office KTP treatment in patients with a range of benign lesions. Laser settings were noted for each patient. Imaging software was then used to calculate a ratio of lesion area to VF length. Ten percent of images were requantified to determine inter-rater reliability. RESULTS: Thirty-two patients underwent 47 procedures for lesions including hemorrhagic polyp, nonhemorrhagic polyp, vocal process granuloma, Reinke's edema, cyst/pseudocyst, leukoplakia, and squamous cell carcinoma in situ. No statistically significant differences were observed with regard to the laser parameters used as a function of lesion type. Regardless, by 1 month following treatment, all lesions had significantly decreased in size, except nonhemorrhagic polyps. Similar data were obtained at 2-month follow-up. We then compared the pre-KTP lesion size with the smallest lesion size quantified during the 1-year follow-up period. All lesions were significantly smaller, with the exception of Reinke's edema. Inter-rater reliability was quite good. CONCLUSIONS: KTP laser effectively reduced VF lesion size, irrespective of the laser parameters used. In addition, our quantification method for lesion size appeared to be both viable and reliable. Laryngoscope, 2011

OBJECTIVE/HYPOTHESIS: The 532-nm KTP laser is clinically useful to induce benign vocal fold lesion regression without a fibrotic response. Previously, we described an in vivo model for KTP-induced injury in the rat larynx. This study uses this model to correlate the KTP-induced histologic and biochemical changes with the absence of long-term vocal fold fibrosis seen in clinical scenarios. STUDY DESIGN: In vivo. METHODS: Unilateral vocal fold injury was induced via KTP laser at 10W (20mS pulse width) as described by our laboratory previously. Animals were subjected to serial endoscopic imaging from postoperative days 1 through 3. Animals were euthanized at 1 day, 4 weeks, and 12 weeks posttreatment and subjected to histologic analyses via hematoxylin and eosin and trichrome staining, as well as RT-PCR analyses for MMP-3, 9, transforming growth factor-beta (TGF-beta), and COX-2 mRNA expression. Uninjured vocal folds were used as controls. RESULTS: Our study revealed gross healing of the vocal fold mucosa by 3 days posttreatment, and an immediate, moderate inflammatory infiltrate with no subsequent ultrastructural changes on histology. MMP-3 and COX-2 expression increased transiently, although no changes were seen in expression of MMP-9, an MMP involved in extracellular matrix remodeling, or TGF-beta, a profibrotic cytokine. CONCLUSIONS: These data suggest that the KTP laser induces a modest inflammatory response, selective MMP expression, and no long-term fibrotic processes in a clinically relevant simulation. Laryngoscope, 2011

The most common primary malignancy of the larynx is the squamous cell carcinoma (SCC). The primary malignant melanoma is quite rare in this location. Less than 60 cases of laryngeal melanomas have been reported to date. To our knowledge, collision primary malignant melanoma and invasive squamous cell carcinoma in the vocal cords has not been reported. We report a 53-year-old male patient who was diagnosed with a collision tumor of laryngeal melanoma and invasive SCC. Multiple Th17 pathway related genes including CTLA-4, IL-17A-F, PLZF, FoxP3, RorgammaT, CD27, and CD70 were analyzed by reverse transcriptase-polymerase chain reaction (Rt-PCR) in this case. Both IL-17A and CD70 genes were detected in this case of collision tumor. The results may define useful biomarkers for early diagnosis of mucosal melanoma and open an immunotherapeutic field for clinical management with the potential benefit from the immunomodulators that enhance both genes