Faculty Bibliography

OBJECTIVES/HYPOTHESIS: We hypothesize that the KTP laser has the potential to augment wound healing in a rat model, and this modality may serve as a therapeutic tool for the management of vocal fold fibrosis. STUDY DESIGN: Prospective, laboratory animal study. METHODS: Rats were subjected to either vocal fold injury +/- KTP laser treatment at low energy to simulate clinically relevant endpoints. In addition, cohorts were subjected to therapeutic KTP laser alone. Endpoints included the analyses of gene expression data related to the acute inflammatory response and extracellular matrix deposition and organization. RESULTS: Therapeutic KTP treatment was associated with an additive effect on inflammatory gene expression in the context of the injured rat vocal fold mucosa. A similar additive effect was observed for matrix metalloproteinase gene expression, similar to data previously reported in the dermatology literature. However, histologically, the KTP had little effect on established vocal fold fibrosis. CONCLUSIONS: These data are the first to attempt to provide mechanistic insight into the clinical utility of angiolytic lasers for vocal fold scar. Similar to previous data obtained in the skin, it appears that these effects are mediated by MMPs. LEVEL OF EVIDENCE: NA. Laryngoscope, 123:2189-2194, 2013.

Introduction: We describe a novel, clinically applicable conduction study of the laryngeal nerves. Methods: Seventeen normal volunteer subjects were included. Activation of the sensory territory of the superior laryngeal nerve was performed by administration of low level brief electrical stimuli. The laryngeal closure reflex (LCR) evoked by this stimulus was recorded by needle electrodes. Mean minimal latencies were calculated for each response, and proposed values for the upper limit of normal were determined. Results: Uniform, consistent early ipsilateral responses and late bilateral responses, which exhibit greater variation in latency and morphology, were recorded. Significant side-to-side differences in latencies were observed, consistent with the length discrepancy between right and left recurrent laryngeal nerves. Conclusions: This technique yields clear, quantifiable data regarding neurologic integrity of laryngeal function, heretofore unobtainable in the clinical setting. This study may yield clinically relevant information regarding severity and prognosis in patients with laryngeal neuropathic injury. Muscle Nerve 47:432-436, 2013.

OBJECTIVES: We utilized dynamic magnetic resonance imaging to visualize the pharynx and upper esophageal segment in normal, healthy subjects. METHODS: A 3-T scanner with a 4-channel head coil and a dual-channel neck coil was used to obtain high-speed magnetic resonance images of subjects who were swallowing liquids and pudding. Ninety sequential images were acquired with a temporal resolution of 113 ms. Imaging was performed in axial planes at the levels of the oropharynx and the pharyngoesophageal segment. The images were then analyzed for variables related to alterations in the area of the pharynx and pharyngoesophageal segment during swallowing, as well as temporal measures related to these structures. RESULTS: All subjects tolerated the study protocol without complaint. Changes in the area of the pharyngeal wall lumen and temporal measurements were consistent within and between subjects. The inter-rater and intra-rater reliabilities for the measurement tool were excellent. CONCLUSIONS: Dynamic magnetic resonance imaging of the swallow sequence is both feasible and reliable and may eventually complement currently used diagnostic methods, as it adds substantive information.

OBJECTIVES/HYPOTHESIS: Although clinical dogma suggests the value of laryngeal visualization (flexible laryngoscopy and stroboscopy) in dysphonic patients, recently published clinical guidelines suggest that, in many cases, history and/or physical examination are sufficient to guide clinical decision-making regarding the timing of such examinations. We sought to prospectively quantify the diagnostic accuracy of history, laryngoscopy, and stroboscopy using direct laryngoscopy as the gold standard. STUDY DESIGN: Expert survey. METHODS: Six laryngologists were presented with vignettes including history and physical examination (HPE), laryngosocpy, and stroboscopy. Questions regarding diagnosis, the certainty of diagnosis, and subsequent management plans were posed. Operative findings via direct laryngoscopy were employed as a comparator. RESULTS: The diagnostic accuracy of HPE was quite low (5%). The accuracy of diagnosis increased substantially following laryngeal imaging; 68.3% for both flexible laryngoscopy and stroboscopy. Particular diagnoses were more consistently identified; cancer, for example, was much more accurately identified on laryngoscopy (100%) and stroboscopy (100%) rather than HPE alone (33%). Cancer was selected as the diagnosis in 10 of 60 HPEs, though was only correct once and missed in five cases. In contrast, no diagnoses of cancer were missed following laryngoscopic and/or stroboscopic examinations. CONCLUSION: These findings confirm the value of laryngeal visualization (flexible laryngoscopy and stroboscopy) in dysphonic patients, and the lack of accuracy of history and physical examination in determining the diagnosis in patients with hoarseness. Laryngoscope, 2013.

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.