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Objectives/Hypothesis The direct study of human phonation is limited by the invasive and painful nature of human laryngeal neuromuscular manipulation. As a platform for the study of human phonation, indirect models have been utilized for decades such as animal, cadaveric, and computational. We sought to develop a research method allowing direct scientific control of virtually living larynges to expand our ability to understand human phonation. Study Design Canine and porcine models. Methods Nineteen canine larynges were surgically removed and reperfused with progressively adapting methodologies to create ex vivo phonation. Results Full neuromuscular stimulation and phonation were ultimately achieved in the ex vivo larynx. As compared with alternative perfusate solutions, heparinized whole blood was found to result in the most robust neuromuscular response. Modification of the reperfusion technique from a continuous flow to a pulsatile pump system resulted in dramatic increases in neuromuscular response and longevity of the organ. The experimental findings were repeated to demonstrate reliability of the ex vivo model. Conclusions The ex vivo larynx model is demonstrated to be a repeatable platform for phonatory research. The process of development has been comprehensively described in the present report. Although the described experimental model was designed for phonatory research, this model can be readily adapted for investigations of organ transplant preservation techniques, effects of organ ischemia, and neuromuscular reinnervation capabilities.

Objective: Eagle's syndrome (ES) or symptomatic elongated styloid process is an uncommon but important cause of chronic head and neck pain. This study reports our experience in the diagnosis and treatment of a series of patients with ES. Study Design: Patient histories, radiographic tests, and operative reports of 3 patients over a 3-month period were prospectively collected. Setting: Tertiary referral otolaryngology service. Results: All patients had resolution of symptoms relating to their elongated styloid processes after surgical resection. Conclusion: Although sometimes clouded by coexisting symptoms, ES can be easily diagnosed based on good history taking and physical examination. If diagnosed appropriately, surgical treatment can be administered promptly. Significance: Patients with ES commonly have a long history of chronic pain treated by multiple physicians. Appropriate diagnosis can lead to prompt treatment of this condition. Ebm Rating: C-4. [ABSTRACT FROM AUTHOR]

Purpose: This study examined the relationship between voice quality and glottal geometry dynamics in patients with adductor spasmodic dysphonia (ADSD)., Method: An objective computer vision and machine learning system was developed to extract glottal geometry dynamics from nasolaryngoscopic video recordings for 78 patients with ADSD. General regression models were used to examine the relationship between overall voice quality and 15 variables that capture glottal geometry dynamics derived from the computer vision system. Two experts in ADSD independently rated voice quality for two separate voice tasks for every patient, yielding four different voice quality rating models., Results: All four of the regression models exhibited positive correlations with clinical assessments of voice quality ( R 2 s = .30-.34, Spearman rho = .55-.61, all with p < .001). Seven to 10 variables were included in each model. There was high overlap in the variables included between the four models, and the sign of the correlation with voice quality was consistent for each variable across all four regression models., Conclusion: We found specific glottal geometry dynamics that correspond to voice quality in ADSD.

Objectives: To identify studies evaluating the epidemiology of recurrent respiratory papillomatosis (RRP), including patient demographics, human papillomavirus (HPV) immunology, clinical course, surgical and medical treatments, and psychosocial factors., Methods: A systematic literature search through PubMed was performed to identify studies evaluating the epidemiological factors associated with RRP. All studies were screened through a priori selection criteria using the titles and abstracts., Results: A total of 208 studies were identified, of which 54 met eligibility criteria and were included in the review., Conclusions: RRP is a rare disease most commonly caused by HPV 6 and 11. It is characterized by recurring benign papillomatous lesions in the respiratory tract, particularly the larynx. Existing evidence about disease risk factors is limited but includes both maternal HPV infection and patient smoking and sexual behaviors. Disease management involves a combination of routine surgical and medical treatment. Surgical techniques include CO 2 -laser, sharp dissection, coblation, microdebridement, and photoangiolytic laser. Medical treatments which have been found to facilitate disease control off-label include interferon-alpha (IFN-α), indole-3-carbinol, acyclovir, bevacizumab, retinoids, and the Gardasil and mumps vaccines. Many patients suffer from additional psychosocial challenges related to their diagnosis. Current disease knowledge remains limited, and more robust controlled trials about risk factors, medical therapies, and surgical options are needed., Level of Evidence: 5., Competing Interests: None., (© 2021 The Authors. Laryngoscope Investigative Otolaryngology published by Wiley Periodicals LLC. on behalf of The Triological Society.)

Objectives: In 2009, the Food and Drug Administration approved the use of the surgical robotic system for removal of benign and malignant conditions of the upper aerodigestive tract. This novel application of robotic-assisted surgery, termed transoral robotic surgery (TORS), places robotic instruments and camera system through the mouth to reach recessed areas of the pharynx and larynx. Over the successive decade, there was a rapid adoption of TORS with a surgical growth rate that continues to increase. Despite the rapid clinical acceptance, the field of TORS has not yet seen substantive changes or advances in the technical shortcomings, the lack of which has restricted objective TORS-specific surgical skills assessment as well as subsequent skills improvement efforts. One of the primary technical challenges of TORS is operating in a confined space, where the robotic system is maneuvered within the restrictive boundaries of the mouth and throat. Due to these confined boundaries of the pharynx, instruments can frequently collide with anatomic structures such as teeth and bone, producing anatomic collisions. Therefore, we hypothesized that anatomic collisions negatively impact TORS surgical performance. Secondarily, we hypothesized that avoidance of unwanted anatomic collisions could improve TORS surgical proficiency., Methods: Design and fidelity testing for a custom TORS training platform with an integrated anatomic collision-sensing system providing real-time tactile feedback is described. Following successful platform assembly and testing, validation study using the platform was carried through prospective surgical training with trial randomization. Twenty otolaryngology-head and neck surgery residents, each trainee performing three discrete mock surgical trials (n = 60), performed the initial system validation. Ten of the 20 residents were randomized to perform the surgical trials utilizing the real-time feedback system. The remaining 10 residents were randomized to perform the surgical trials without the feedback system, although the system still could record collision data. Surgical proficiency was measured by Global Evaluative Assessment of Robotic Skills (GEARS) score, time to completion, and tumor resection scores (categorical scale ranging 0-3, describing the adequacy of resection)., Results: Major anatomic collisions (greater than 5N of force) negatively affected GEARS robotic skills. A mixed model analysis demonstrated that for every additional occurrence of a major collision, GEARS robotic skills assessment score would decrease by 0.29 points (P = .04). Real-time collision awareness created significantly fewer major (> 5 N) anatomic collisions with the tactile feedback system active (n = 30, mean collisions = 2.9 ± 4.2) as compared with trials without tactile feedback (n = 30, mean collisions = 12.53 ± 23.23) (P < .001). The second assessment measure of time to completion was unaffected by the presence of collisions or by the use of tactile feedback system. The third proficiency assessment was measured with tumor resection grading. Tumor resection scores was significantly (P = .02) improved with collision awareness system activated than trials without collision awareness., Conclusion: In order to test our primary hypothesis, a novel TORS training platform was successfully developed that provides collision force measurements including frequency, severity, and duration of anatomic collisions. Additionally, the platform was modulated to provide real-time tactile feedback of the occurrence of out-of-field collisions. Utilizing this custom platform, our hypothesis that anatomic collisions during TORS diminishes surgical performance was supported. Additionally, our secondary hypothesis that subsequent reduction of anatomic collisions improves TORS proficiency was supported by the surgical trial. Dedicated investigation to characterize the effect size and clinical impact is required in order to translate this finding into training curriculums and into clinical utilization., Level of Evidence: II (Randomized trial) Laryngoscope, 130:S1-S17, 2020., (© 2020 American Laryngological, Rhinological and Otological Society Inc, "The Triological Society" and American Laryngological Association (ALA).)

Objective: Laryngotracheal stenosis is one of the most difficult conditions treated by the Otolaryngologist. Open resection of stenosis with primary airway anastomosis is the definitive treatment for this condition. However, some patients are considered high risk candidates for open airway surgery and management and outcomes in this group have not been reported. The purpose of this investigation is to identify a series of high risk patients who underwent open laryngotracheal surgery and detail the lessons learned in regards to their post-operative course and outcomes., Methods: A retrospective cohort study of all patients that underwent airway resection and primary anastomosis over a fifteen-year period was performed. High-risk patients, those with medical comorbidities that impair wound healing, were identified. Post-operative course, management of complications, and ultimate airway outcomes were noted., Results: Seven patients fitting the high-risk category were identified. Comorbidities were poorly controlled insulin dependent diabetes mellitus (N = 4), poorly controlled hypertension (N = 4), end stage renal disease requiring hemodialysis (N = 3), chronic obstructive pulmonary disease (N = 1), and history of radiation therapy (N = 1). Each patient suffered postoperative complications of varying degrees including postoperative infection (N = 1), formation of granulation tissue at the anastomotic site (N = 3), and postoperative hematoma (N = 1). Management included treatment of infection and complications. Anastomotic dehiscence was managed with tracheostomy and T-tubes., Conclusions: High-risk medical comorbidities may not be absolute contraindications for open laryngotracheal resection of airway stenosis. However, this experience emphasizes the importance of preoperative medical optimization and comprehensive postoperative care., Competing Interests: The authors have declared that no competing interests exist.

Objectives: Early in his career, David Lim recognized the scientific impact of genetically anomalous mice exhibiting otoconia agenesis as models of drastically compromised vestibular function. While these studies focused on the mutant pallid mouse, contemporary genetic tools have produced other models with engineered functional modifications. Lim and colleagues foresaw the need to analyze vestibular epithelia from pallid mice to verify the absence of downstream consequences that might be secondary to the altered load represented by otoconial agenesis. More generally, however, such comparisons also contribute to an understanding of the susceptibility of labyrinthine sensory epithelia to more widespread cellular changes associated with what may appear as isolated modifications., Methods: Our laboratory utilizes a model of vestibular hypofunction produced through genetic alteration, the otoferlin-null mouse, which has been shown to exhibit severely compromised stimulus-evoked neurotransmitter release in type I hair cells of the utricular striola. The present study, reminiscent of early investigations of Lim and colleagues that explored the utility of a genetically altered mouse to explore its utility as a model of vestibular hypofunction, endeavored to compare the expression of the hair cell marker oncomodulin in vestibular epithelia from wild-type and otoferlin-null mice., Results: We found that levels of oncomodulin expression were much greater in type I than type II hair cells, though were similar across the 3 genotypes examined (ie, including heterozygotes)., Conclusion: These findings support the notion that modifications resulting in a specific component of vestibular hypofunction are not accompanied by widespread morphologic and cellular changes in the vestibular sensory epithelia.

Introduction: Abductor spasmodic dysphonia, a difficult-to-treat laryngologic condition, is characterized by spasms causing the vocal folds to remain abducted despite efforts to adduct them during phonation. Traditional treatment for abductor spasmodic dysphonia-botulinum toxin injection into the posterior cricoarytenoid muscle-can be both technically challenging and uncomfortable. Due to the difficulty of needle placement, it is often unsuccessful. The purpose of this investigation is to present a previously undescribed treatment for abductor spasmodic dysphonia-bilateral vocal fold medialization., Methods: A retrospective case review of all cases of abductor spasmodic dysphonia treated in a tertiary care laryngology practice with bilateral vocal fold medialization over a 10-year period was performed. The Voice Handicap Index and the Voice-Related Quality of Life surveys were utilized to assess patient satisfaction with voice outcome., Results: Six patients with abductor spasmodic dysphonia treated with bilateral vocal fold medialization were identified. Disease severity ranged from mild to severe. All six patients reported statistically significant improvement in nearly all Voice Handicap Index and Voice-Related Quality of Life parameters. They reported fewer voice breaks and greater ease of communication. Results were noted immediately and symptoms continue to be well controlled for many years following medialization., Conclusions: Bilateral vocal fold medialization is a safe and effective treatment for abductor spasmodic dysphonia. It is performed under local anesthesia and provides phonation improvement in the short and long term., (Copyright © 2019 The Voice Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Tongue fibrosis resulting from head and neck cancer, surgery, radiation, chemotherapy, or a combination thereof devastates one's quality of life. Therapeutic options are limited. Here we investigate human bone marrow-derived multipotent stromal cells (MSC) as a novel injectable treatment for post-injury tongue fibrosis., Methods: MSCs were grown in culture. Eighteen athymic rats underwent unilateral partial glossectomy. After two weeks for scar formation, a single injection was performed in the tongue scar. Three treatment groups were studied: low and high concentration MSC, and control media injection. Tongues were harvested for evaluation at three weeks post-treatment., Results: Dense fibrosis was achieved in control animals at five weeks. High concentration MSC reduced cross sectional scar burden ( P = .007) and pathologic score for inflammation and fibrosis., Conclusion: This study establishes the feasibility of a novel rodent tongue fibrosis model, and begins to assess the utility of human MSCs to reduce scar burden., Level of Evidence: N/a.

Importance: Optimal management of subglottic stenosis has not been established. Endoscopic techniques include balloon dilation, radial incisions with carbon dioxide laser or cold knife, and combinations of techniques. Adjunctive measures include mitomycin application and glucocorticoid injection., Objective: To determine whether surgical technique or adjunctive measures are associated with duration between surgical procedures., Design, Setting, and Participants: Adult patients with subglottic stenosis treated endoscopically between 1995-2015 at a quaternary academic medical center were identified. Patients with isolated subglottic (cricotracheal) stenosis 18 years and older were included. Patients with prior open surgical procedures, prior laryngeal surgical procedures, glottic stenosis, or vocal fold paralysis were excluded., Interventions: Patients underwent endoscopic procedures including laser radial incisions, balloon dilation, or both, with some patients receiving topical mitomycin, glucocorticoid injection, or both., Main Outcomes and Measures: Time interval between endoscopic treatments., Results: A total of 101 patients (mean [SD] age, 52.3 [15.9] years; 77.2% female) were included in the analysis, with etiologies including idiopathic (47 [46.5%]), intubation (31 [30.7%]), granulomatosis with polyangiitis (9 [8.9%]), and other autoimmune diseases (6 [5.9%]). Among the 219 operations, both laser and balloon dilation were used in 117 (53.4%), while balloon dilation alone was used in 96 (43.8%) and laser alone in 6 (2.7%). Mitomycin application and steroid injection were used in 144 (65.8%) and 93 (42.5%) cases, respectively. Mitomycin application was associated with improvement in the mean interval to next procedure from 317 to 474 days (absolute difference, 157 days; 95% CI, 15-299 days). Advanced grade of stenosis, dilation technique, and steroid injection did not significantly alter the surgical intervals., Conclusions and Relevance: Endoscopic surgery for subglottic stenosis is a critical aspect of patient management. Neither surgical technique nor grade of stenosis was seen to alter the surgical intervals. Mitomycin application was associated with an extended time interval between endoscopic treatments.

Importance: Scientific understanding of human voice production to date is a product of indirect investigations including animal models, cadaveric tissue study, or computational modeling. To our knowledge, direct experimentation of human voice production has previously not been possible owing to its invasive nature. The feasibility of an ex vivo perfused human phonatory model has recently allowed systematic investigation in virtually living human larynges with parametric laryngeal muscle stimulation., Objective: To investigate the association between adductor muscle group stimulation and the open quotient (OQ) (the fraction of the cycle during which the glottis remains open) of vocal fold vibration., Design, Setting, and Participants: An ex vivo perfused human tissue study was conducted at a physiology laboratory. Human larynx recovered from organ donors within 2 hours of cardiac death was used. The study was performed on May 19, 2014; data analysis took place from June 1, 2014, to December 15, 2014., Interventions: Perfusion with donated human blood was reestablished shortly after cardiac death. Ex vivo perfused human phonation was then achieved by providing subglottal airflow under graded neuromuscular electrical stimulation bilaterally to the intrinsic adductor groups and cricothyroid muscles., Main Outcomes and Measures: Phonation resulting from the graded states of neuromuscular stimulation was evaluated using high-speed vibratory imaging; the OQ was derived through digital kymography and glottal area waveform analysis., Results: During constant glottal flow, a stepwise increase in adductor muscle group stimulation decreased the OQ. Quantitatively, OQ values decreased with increased stimulation levels from 2 V (OQ, 1) to 5 V (OQ, 0.68) and reached a lower limit of 8 V (OQ, 0.42). Increased stimulation above maximal muscle deformation was unable to affect OQ beyond this lower limit., Conclusions and Relevance: To our knowledge, a negative association between adductor muscle group stimulation and phonatory OQ has been demonstrated for the first time in a neuromuscularly activated human larynx. Further experience with the ex vivo perfused human phonatory model will aid in systematically defining this causal relationship.

Objective: Cricotracheal resection (CTR) and laryngotracheoplasty (LTP) are open surgical treatments for severe subglottic stenosis. This study aims to compare the applications and outcomes of these techniques., Method: Patients with subglottic stenosis at a tertiary academic institution from 2000 to 2012 were identified by diagnosis codes. Patients who underwent LTP or CTR were included. Records were reviewed for treatment data and outcomes. Patients with a history of head and neck malignancy or stenosis without cricoid involvement were excluded., Result: Sixty-one and 20 patients underwent LTP and CTR, respectively. When comparing patients receiving LTP and CTR, there was a significant difference in stenosis etiology (P=.014). The groups were similar in Cotton-Myer grade (P=.102). At last follow-up, 80.3% of LTP patients and 90.0% of CTR patients were decannulated. On multivariate analysis, there was a significant association between stenosis grade and decannulation in the LTP group (P=.01). Decannulation was not associated with stenosis grade in the CTR group. In both groups, there was no significant association between decannulation and sex, stenosis etiology, or stenosis length., Conclusion: Cricotracheal resection and LTP have both shown excellent long-term decannulation rates. Etiology and stenosis grade are likely to be determining factors when recommending specific surgical interventions for subglottic stenosis., (© The Author(s) 2014.)

Importance: This study reviews a single center's experience of performing staged laryngotracheoplasty (LTP) for the treatment of laryngotracheal stenosis with the ultimate goal of attaining long-term airway patency without restenosis., Objective: To identify staged LTP as an efficacious surgical treatment option for laryngotracheal stenosis., Design, Setting, and Participants: From January 2000 to January 2012, patients at a tertiary care academic institution presenting with diagnoses of laryngeal or laryngotracheal stenosis were retrospectively identified. Medical records from adult patients were inspected, and patient demographics, clinical data, and clinical outcomes were recorded. All patients undergoing staged LTP were initially included. Patients with history of head and neck malignant neoplasm were excluded., Interventions: Staged LTP., Main Outcomes and Measures: The primary outcome was long-term decannulation, defined as decannulation for duration of at least 6 months., Results: Sixty-one patients were included in this study. The mean (SD) patient age was 47.1 (16.7) at the time of first-stage LTP and had a mean (range) follow-up of 5.32 (0.5-17.3) years from the first-stage reconstruction. Etiology of stenosis included prolonged intubation in 27 patients (44%), autoimmune disease in 9 (15%), idiopathic causes in 11 (18%), blunt laryngeal trauma in 10 (16%), and other causes in 4 (7%). Forty-nine patients (80%) were successfully decannulated, while to date 12 (20%) remain tracheostomy or tympanostomy tube dependent. Univariate analyses showed no significant association between decannulation and age (P = .35), sex (P = .52), history of intubation (P = .22), surgeon (P = .20), etiology of stenosis (P = .91), or length of stenosis (P = .31). Multivariate logistic regression analysis showed a significant inverse relationship between grade of stenosis and probability of decannulation (P = .01)., Conclusions and Relevance: Staged LTP is an option for the reconstruction laryngotracheal stenosis. Our experience shows excellent decannulation rates in the selected patients with stenosis, many of whom have failed treatment with other surgical modalities.

Sclerosing polycystic adenosis is an extremely uncommon, recently described, sclerosing lesion of the salivary glands that appears histologically similar to fibrocystic changes of the breast. The key histopathologic features of sclerosing polycystic adenosis include lobular proliferation of ductal and acinar elements, cystically dilated ducts exhibiting frequent apocrine and sebaceous metaplasia, eosinophilic intracytoplasmic granules within some acinar-type cells, intraductal epithelial hyperplasia, and dense fibrosis. Most described cases have occurred in the major salivary glands, particularly the parotid gland. Although most authorities consider sclerosing polycystic adenosis to be a pseudoneoplastic process, the occurrence of dysplasia and carcinoma in situ of ductal epithelium reported recurrence rates of up to 30%, and recent evidence of clonality suggests a possible neoplastic etiology. However, there have been no cases of metastasis. Herein, we report the first case of sclerosing polycystic adenosis of the sinonasal tract in a 79-year-old woman presenting with a sinonasal mass., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Selective laryngeal adductor denervation-reinnervation surgery (SLAD-R) offers a viable surgical alternative for patients with adductor spasmodic dysphonia refractory to botulinum toxin injections. SLAD-R selectively denervates the symptomatic thyroarytenoid muscle by dividing the distal adductor branch of the recurrent laryngeal nerve (RLN), and preventing reinnervation, by the proximal RLN and maintaining vocal fold bulk and tone by reinnervating the distal RLN with the ansa cervicalis. We present a patient who had previously undergone successful SLAD-R but presented 10 years postoperatively with a new regional dystonia involving his strap muscles translocated to his reinnervated larynx by his previous ansa-RLN neurorraphy. The patient's symptomatic vocal fold adduction resolved completely on division of the ansa-RLN neurorraphy confirming successful selective functional reinnervation of vocal fold adductors by the ansa cervicalis., (Copyright © 2012 The Voice Foundation. Published by Mosby, Inc. All rights reserved.)

Objectives: Currently, botulinum toxin (Botox) injection is the standard of treatment for adductor spasmodic dysphonia (ADSD). We sought to compare the outcome of selective laryngeal adductor denervation-reinnervation (SLAD-R) surgery for ADSD to that of Botox injections., Methods: Patient-oriented measures (VHI-10) and objective single-blinded gradings of digital voice recordings were utilized as outcome measures. The surgical cohort, recruited by retrospective patient selection, consisted of 77 patients with a mean follow-up time of 7.54 +/- 2.55 years (range, 2.2 to 14.2 years). The injection cohort, recruited prospectively, included 28 patients with a mean follow-up time of 46.37 +/- 5.51 days (range, 36 to 54 days)., Results: As measured by the VHI-10, the surgical patients had significantly improved voice handicap outcome scores (mean, 14.4 +/- 13.6) as compared to the patients who had Botox injection (mean, 26.5 +/- 12.1; p = 0.001). Aside from VHI-10 item 2, the surgical group demonstrated significantly improved voice-related function on each VHI-10 component (p = 0.01). Within the injection subgroup, 88% agreed that Botox successfully treats their ADSD, yet only 63% agreed that Botox improves their speech consistently. Within the surgical subgroup, 82% would recommend this surgery to others, and 78% agreed that their voice was actually better after surgery than after Botox. Objective voice ratings demonstrated similar levels of breathiness and overall voice quality in the treatment subgroups., Conclusions: When indicated, the SLAD-R surgery for ADSD demonstrates outcomes equal to or superior to those of the current standard of Botox injections.

Objective: Laryngeal trauma is an infrequent diagnosis with a scarcity of published data. We aim to further define the factors associated with positive surgical outcomes of adult laryngeal trauma., Study Design: Multi-institution database analysis., Methods: Of the 1.9 million trauma cases from the National Trauma Database (NTDB), 564 adult trauma events were selected with ICD-9 codes specific to laryngeal trauma., Results: Laryngeal trauma was seen predominately in white (61.5%), middle-aged (40.6 years), male (83.7%) patients experiencing blunt (70.7%) laryngeal injury with multiorgan system (92.2%) trauma. There was an overall 17.9% mortality rate. Within the 564 cases, 133 direct laryngoscopies, 185 tracheostomies, 53 laryngeal suturing, and 60 laryngeal fracture repairs were performed. In univariate negative binomial regression models, trauma severity (P ≤ .01), placement of tracheostomy (P lt; .01), and delayed tracheostomy placement (P = .04, .03, .048) were associated with increased ventilator dependence, intensive care unit (ICU) stay, and overall hospital admission duration. Multivariate regression models demonstrated significant associations between tracheostomy performed within 24 hours and shortened ICU stay (P = .03, β = -.28, SE = 1.7) and overall hospital stay (P = .009, β = -.23, SE = 3.1)., Conclusions: The NTDB allows study of the largest laryngeal trauma cohort in modern literature. Although complexities arise in the treatment of laryngeal traumas, when indicated, surgical airway should be placed within 24 hours of presentation to improve the overall hospital course., (Copyright © 2011 The American Laryngological, Rhinological, and Otological Society, Inc.)

Objectives/hypothesis: Selective reinnervation of the posterior cricoarytenoid muscle with a single phrenic nerve rootlet has been shown to restore physiologic motion in animal models. However, clinical translation of this work is challenged by the limited knowledge of the cervical anatomy of the phrenic nerve., Study Design: Prospective collaborative study., Methods: Dissection of 111 cadaveric necks (88 embalmed and 23 unembalmed) from 56 cadavers., Results: The mean (standard deviation) lengths of unembalmed cadaver C3, C4, and C5 nerve rootlets were 3.9 (2.4), 3.6 (2.6), and 0.5 (0.8) cm, respectively. Embalmed cadavers had shorter C3 and C4 phrenic nerve rootlet lengths than unembalmed cadavers (P = .02 and P = .03, respectively). There was no difference in mean nerve rootlet length based on sex, body height or weight, or side of dissection. A total of eight unique phrenic nerve rootlet patterns were identified. The most common pattern consisted of phrenic with single C3 and C4 rootlets with an immeasurable C5 rootlet, which was present in 30 of 111 (26%) of the necks. The classic three branching pattern of single C3, C4, and C5 rootlets was found in 25 of 111 (22%) of the necks. Six of 111 (5%) of the dissections displayed accessory phrenic nerves arising from the C3, C4, or C5 anterior rami. A χ(2) analysis showed no difference between side or sex and frequency of pattern., Conclusions: The present study demonstrates the wide variability within the cervical anatomy of the phrenic nerve., (Copyright © 2011 The American Laryngological, Rhinological, and Otological Society, Inc.)

Bronchogenic cysts with malignant change are rarely reported. We describe a case of poorly differentiated adenocarcinoma arising from a cervical bronchial cyst in a patient presenting with a thyroid mass, cervical lymphadenopathy, and initial biopsy suggestive of papillary thyroid carcinoma. The clinical presentation, intraoperative findings, radiographic images, and pathology slides are presented. To our knowledge, this is the first report of a poorly differentiated adenocarcinoma arising from a bronchial cyst in the cervical region., (Copyright © 2011 The American Laryngological, Rhinological, and Otological Society, Inc.)

Objectives: This study evaluated the safety and effectiveness of injection of autologous fibroblasts into the lamina propria layer to treat vocal fold scarring., Study Design: A prospective, open-label, single arm, pilot study at a single tertiary care center., Methods: Autologous fibroblasts were expanded in cell culture from punch biopsies of the buccal mucosa of five human subjects with vocal fold scarring. Three doses of 1-2 × 10(7) cells/mL were injected into the superficial lamina propria layer of each scarred vocal fold at four-week intervals. The primary efficacy measure was an objective evaluation of the mucosal wave grade; secondary measures included acoustic analyses, a patient-completed voice handicap index (VHI) survey, and voice quality questionnaire. Safety assessments included clinical laboratory blood tests, vital signs, and monitoring for adverse events. Patients were followed for 12 months following the first treatment., Results: Mucosal wave grade improved and the improvement was sustained through month 12. Sustained improvements through month 12 were also noted for the VHI and voice quality questionnaire. Multiple injections of autologous fibroblasts into the lamina propria were well tolerated. Temporary otalgia was noted following treatment in two subjects., Conclusions: This study demonstrates that injection of autologous fibroblasts into the scarred vocal fold lamina propria layer is safe. Sustained trends for improved outcome were supported by 12-month data for mucosal wave grade, VHI, and voice quality questionnaire., (Copyright © 2011 The American Laryngological, Rhinological, and Otological Society, Inc.)

Objectives: Tissue engineering may provide a treatment for severe vocal fold scars. This study quantifies mechanical properties and demonstrates vibration of a tissue-engineered vocal fold cover replacement., Methods: Tissue-engineered constructs were produced from fibrin and adipose-derived stem cells. Optimized bilayered constructs contained epithelial and mesenchymal cell phenotypes in a stratified geometry. For comparison, homogeneous constructs did not have epithelial differentiation. Elastic modulus was determined using indentation. Immunohistochemical labeling for type I collagen was performed. A bilayered construct was also tested in phonation in an excised larynx model., Results: Bilayered vocal fold cover replacements had indentation moduli similar to human vocal fold covers (mean construct modulus 6.8 kPa). Collagen deposition occurred in the middle of the construct. Homogeneous constructs had a mean modulus of 8.3 kPa, and collagen was concentrated at the surface. An excised larynx with unilateral vocal fold cover replacement phonated and exhibited mucosal waves at physiologic airflow., Conclusion: Bilayered tissue-engineered constructs were produced that exhibited indentation modulus, microstructure, and vibration similar to that exhibited by human vocal fold covers., (Copyright 2010 American Academy of Otolaryngology-Head and Neck Surgery Foundation. Published by Mosby, Inc. All rights reserved.)

Objectives/hypothesis: One potential treatment option for severe vocal fold scarring is to replace the vocal fold cover layer with a tissue-engineered structure containing autologous cells. As a first step toward that goal, we sought to develop a three-dimensional cell-populated matrix resembling the vocal fold layers of lamina propria and epithelium., Study Design: Basic science investigation., Methods: Adipose-derived stem cells were cultured in fibrin hydrogels with various growth factors. At the end of the culture period, matrices were sectioned and labeled with immunomarkers to identify cell phenotype., Results: Adipose-derived stem cells survived, attached, and populated three-dimensional fibrin matrices. Under select conditions, a superficial layer of cells expressing epithelial marker proteins overlay a deeper mesenchymal cell layer., Conclusions: A three-dimensional structure of fibrin and adipose-derived stem cells was created as a prototype vocal fold replacement. Two segregated cell phenotypes occurred, producing a bilayered structure resembling epithelium over lamina propria. This preliminary work demonstrates the feasibility of tissue engineering to produce structures for vocal fold replacement.

Objectives: To perform preliminary measurements of the shear modulus of the vocal fold cover layer during intrinsic laryngeal muscle contraction., Study Design: Shear modulus was measured in an in vivo canine larynx and an ex vivo human larynx., Methods: Shear stress was applied to the transverse axis of the vocal fold using a modified linear skin rheometer (LSR) via an attached suction probe. The probe displacement in response to the applied force was measured at various levels of laryngeal muscle contraction. The force-displacement data were used to derive the shear modulus using a simple shear model. In the ex vivo human larynx, lateral cricoarytenoid (LCA) muscle and cricothyroid (CT) muscle activity was simulated with arytenoid adduction and cricothyroid approximation sutures, respectively. In the in vivo canine, adductor muscle and CT muscle contraction was induced with graded stimulation of the recurrent laryngeal nerve (RLN) and the superior laryngeal nerves (SLN), respectively., Results: : Baseline shear modulus was between 1,076 and 1,307 Pascals. In the ex vivo human larynx, the shear modulus increased gradually to a maximum of 1.6 times baseline value with graded arytenoid adduction and 3.7 times baseline value with cricothyroid approximation. In the in vivo larynx, the shear modulus increased to a maximum of 1.6 times baseline value with RLN stimulation and 2.5 times baseline value with SLN stimulation., Conclusions: Findings are in agreement with the cover-body model in that cricothyroid muscle activity generates a greater change in cover stiffness than laryngeal adductors. The role of the individual laryngeal adductors (thyroarytenoid [TA] vs. LCA) in control of vocal fold cover stiffness remains to be further elucidated.

Objective: To identify research priorities to increase understanding of the pathogenesis, diagnosis, and improved treatment of spasmodic dysphonia., Study Design and Setting: A multidisciplinary working group was formed that included both scientists and clinicians from multiple disciplines (otolaryngology, neurology, speech pathology, genetics, and neuroscience) to review currently available information on spasmodic dysphonia and to identify research priorities., Results: Operational definitions for spasmodic dysphonia at different levels of certainty were recommended for diagnosis and recommendations made for a multicenter multidisciplinary validation study., Conclusions: The highest priority is to characterize the disorder and identify risk factors that may contribute to its onset. Future research should compare and contrast spasmodic dysphonia with other forms of focal dystonia. Development of animal models is recommended to explore hypotheses related to pathogenesis. Improved understanding of the pathophysiology of spasmodic dysphonia should provide the basis for developing new treatment options and exploratory clinical trials., Significance: This document should foster future research to improve the care of patients with this chronic debilitating voice and speech disorder by otolaryngology, neurology, and speech pathology.

Objectives: We evaluated cross-linked hyaluronic acid (hylan B gel) as a scaffold for tissue regeneration and mucosal wave restoration in carbon dioxide laser-ablated canine vocal folds., Methods: Five beagles underwent stroboscopy before ablation of the left vocal fold with a carbon dioxide laser. Four weeks later, stroboscopy was repeated before and after submucosal injection of hylan B gel into the left vocal fold of 4 animals and of saline solution in 1 animal. Stroboscopy was repeated 12 weeks later, and histologic analysis was performed., Results: Four weeks after laser ablation, all animals had soft tissue defects and absence of mucosal waves. Hylan B injection restored mucosal waves, and saline injection did not. Twelve weeks after injection, hylan B-injected larynges had tissue regeneration and mucosal waves, and the saline-injected larynx had neither. Histology showed regenerated lamina propria with residual foci of hylan B in the hylan B-injected larynges and dense submucosal scar in the saline-injected animal., Conclusions: Submucosal hylan B gel injection in laser-ablated canine vocal folds restored tissue volume and mucosal waves and facilitated functional tissue regeneration over 12 weeks. Hylan B gel may have utility as a soft tissue scaffold for rehabilitation of phonatory function in vocal folds with lamina propria defects.

Objectives: Although excised laryngeal models and physical models of the larynx are important in the study of laryngeal dynamics, they cannot be used to study the influence of neuromuscular contraction on vocal fold vibration, especially with regard to the thyroarytenoid muscle. Our aim was to develop an ex vivo larynx model of phonation, and combine the benefits of the in vivo and excised laryngeal models to the ex vivo situation., Methods: Three canine larynges were surgically removed and perfused ex vivo with modified Krebs-Henseleit reperfusion solution. The laryngeal nerves were stimulated, and an assessment of neuromuscular viability, phonation, and vocal fold vibration was made., Results: Neuromuscular stimulation, phonation, and experimental manipulation were possible for several hours after the onset of ex vivo perfusion. Repeatable periodic phonation in short bursts was achieved. Perfusion appears critical to maintain ex vivo viability, as adductory force was almost immediately lost upon cessation of ex vivo perfusion., Conclusions: The ex vivo larynx model has the potential to facilitate the measurement of glottal variables in a neuromuscularly correct model. We propose that the further development of this laryngeal model may be useful in the study of laryngeal dynamics, particularly when invasive measurements, such as that of glottal exit flow, are required.

Objectives: Our aim was to present laryngovideostroboscopic findings in unilateral superior laryngeal nerve paresis and paralysis., Study Design and Setting: Retrospective case review, academic voice clinic., Methods: Blinded retrospective review of videostroboscopic recordings from cases confirmed by laryngeal electromyography., Results: Three cases of unilateral superior laryngeal nerve paresis and paralysis were identified. At rest, there were no common abnormal laryngeal findings. Upon phonation, common findings were ipsilateral vocal fold bowing and shortening, vocal process height asymmetry with the ipsilateral vocal process overriding the normal, and ipsilateral hyperadduction of the false vocal fold., Conclusions: The common features noted in these cases of laryngeal electromyography-proved uSLNp could be used to make a presumptive diagnosis of this disorder.

Objective: Our aim was to review the safety of percutaneous injection laryngoplasty using bovine crosslinked collagen, focusing specifically on two often-stated concerns: injecting patients who are taking the anticoagulant medication warfarin, and injecting patients without prior skin hypersensitivity testing., Study Design and Setting: Retrospective chart review of injection laryngoplasty performed between 1997 and 2006 at the University of California, Los Angeles., Results: The study group consisted of 895 patients who underwent 1290 injection laryngoplasty procedures. No bleeding complications were noted in 59 patients taking warfarin. No allergic complications were reported in 845 patients who did not undergo skin hypersensitivity testing before injection laryngoplasty., Conclusion: Percutaneous bovine crosslinked collagen injection laryngoplasty is safe in patients taking warfarin. Skin testing for hypersensitivity does not appear to be necessary before injection., Significance: Patients on warfarin are candidates for injection laryngoplasty without the need to discontinue the medication. Eliminating skin hypersensitivity testing before percutaneous bovine crosslinked collagen injection laryngoplasty allows for a prompt treatment of glottic insufficiency.

The clinical diagnosis of superior laryngeal nerve paralysis (SLNp) is infrequently made, because of the heterogeneity of clinical presentations and laryngoscopic findings. Laryngeal electromyography (LEMG) can provide the definitive diagnosis of this abnormality. With increasing use of LEMG in clinical practice, this condition is now more frequently appreciated by otolaryngologists. A characteristic, but infrequently reported, videostroboscopic vocal fold motion termed Gegenschlagen ("dashing-against-each-other") has previously been described to occur in unilateral SLNp. We encountered such motion in a clinical case, which we subsequently verified as unilateral SLNp by means of LEMG. This characteristic glottic motion was then verified in an in vivo canine model of phonation after unilateral SLNp. Videostrobokymography was performed to generate kymograms that illustrated this vocal fold motion clearly. Kymograms of both human and canine subjects with SLNp demonstrated an undulating motion of the horizontally shifting glottic space as the medial edges of the vocal folds chased each other 90 degrees out of phase. As one vocal fold mucosal edge was opening, the other was closing, and this repeated motion appeared as vocal folds chasing or dashing against each other. Although not uniformly seen in all cases, this vocal fold motion appears to be unique to SLNp.

Objective: Knowledge of the location of the muscular process of the arytenoid cartilage and the recurrent laryngeal nerve is essential to performing a successful arytenoid adduction and laryngeal reinnervation surgery. We describe external landmarks useful in locating these structures., Study Design: Cadaveric laryngeal dissection., Methods: Posterior laryngeal dissection was performed in 16 human larynges. The position of the muscular process of the arytenoid was measured bilaterally relative to the inferior and superior borders of the thyroid lamina. The recurrent laryngeal nerve was followed distally from slightly below the level of the cricothyroid joint to its genu where its vertical course changes to an oblique intralaryngeal course., Results: The muscular process of the arytenoid was usually found halfway between the roots of the superior and inferior cornu of the thyroid lamina. The recurrent laryngeal nerve was found just deep to the cricothyroid joint and lateral to the posterior cricoarytenoid muscle. There were no other nerves in this area., Conclusions: This study finds that the superior and inferior borders of the thyroid lamina are useful intraoperative landmarks to locate the muscular process of the arytenoid. The cricothyroid joint provides a good starting point to locate the recurrent laryngeal nerve, which can be identified slightly deeper between it and the posterior cricoarytenoid muscle.

Objective: To examine the antigenic distribution of human leukocyte antigens (HLA) of the human larynx., Study Design and Setting: Twelve human larynges were examined for Class I (HLA-A, -B, -C) and Class II (HLA-DR) histocompatibility antigens using mouse monoclonal antibodies in an indirect immunoperoxidase assay. Structures of the larynx and surrounding tissues were examined and given a semiquantitative score based on HLA Class I and II expression., Results: The mucosal surface epithelium of the larynx stains 2+ or stronger for HLA Class I antigens and 1+ for Class II antigens. The deeper submucosal glands stain 1+ for Class I antigens and 2+ or stronger for Class II antigens. Thyroid cartilage showed 2+ or stronger staining of the chondrocytes for Class I antigens only. Thyroid follicular cells also stain only for Class I antigens. Perichondrium and Schwann cells of nerves stain stronger for Class I antigens than Class II antigens. Cartilage matrix, muscle cells, and axons of nerves do not stain for either class of antigens. Endothelium stains 3+ for both classes of antigens., Conclusions: The detailed distribution of major transplantation antigens in the human larynx is elucidated. Class II antigens implicated as initiators of organ transplant rejection were primarily found in 6 areas: mucosal surface epithelium, submucosal glands, ducts, vascular endothelium, perichondrium, and Schwann cells of nerves. The relevance of these findings to the initiation and detection of laryngeal allograft graft rejection is discussed.

There is no good surgical, medical or prosthetic solution to the problems faced by those with a larynx whose function is irreversibly damaged by tumor or trauma. Over the past 10 years, the pace of research designed to establish laryngeal transplantation as a therapeutic option for these persons has increased steadily. The biggest milestone in this field was the world's first true laryngeal transplant performed in Cleveland, Ohio in 1998. The recipient's graft continues to function well, in many respects, even after 7 years. However, it has also highlighted the remaining barriers to full-scale clinical trials. Stimulated by these observations, several groups have accumulated data which point to answers to some of the outstanding questions surrounding functional reinnervation and immunomodulation. This review seeks to outline the progress achieved in this field by 2005 and to point the way forward for laryngeal transplantation research in the 21st century.

Objectives/hypothesis: The purpose of this study was to measure the medial surface dynamics of a canine vocal fold during phonation. In particular, displacements, velocities, accelerations, and relative phase velocities of vocal fold fleshpoints were reported across the entire medial surface. Although the medial surface dynamics have a profound influence on voice production, such data are rare because of the inaccessibility of the vocal folds., Study Design: Medial surface dynamics were investigated during both normal and fry-like phonation as a function of innervation to the recurrent laryngeal nerve for conditions of constant glottal airflow., Methods: An in vivo canine model was used. The larynx was dissected similar to methods described in previous excised hemilarynx experiments. Phonation was induced with artificial airflow and innervation to the recurrent laryngeal nerve. The recordings were obtained using a high-speed digital imaging system. Three dimensional coordinates were computed for fleshpoints along the entire medial surface. The trajectories of the fleshpoints were preprocessed using the method of Empirical Eigenfunctions., Results: Although considerable variability existed within the data, in general, the medial-lateral displacements and vertical displacements of the vocal fold fleshpoints were large compared with anterior-posterior displacements. For both normal and fry-like phonation, the largest displacements and velocities were concentrated in the upper medial portion. During normal phonation, the mucosal wave propagated primarily in a vertical direction. Above a certain threshold of subglottal pressure (or stimulation to the recurrent laryngeal nerve), an abrupt transition from chest-like to fry-like phonation was observed., Conclusions: The study reports unique, quantitative data regarding the medial surface dynamics of an in vivo canine vocal fold during phonation, capturing both chest-like and fry-like vibration patterns. These data quantify a complex set of dynamics. The mathematical modeling of such complexity is still in its infancy and requires quantitative data of this nature for development, validation, and testing.

Quantitative measurement of the medial surface dynamics of the vocal folds is important for understanding how sound is generated within the larynx. Building upon previous excised hemilarynx studies, the present study extended the hemilarynx methodology to the in vivo canine larynx. Through use of an in vivo model, the medial surface dynamics of the vocal fold were examined as a function of active thyroarytenoid muscle contraction. Data were collected using high-speed digital imaging at a sampling frequency of 2000 Hz, and a spatial resolution of 1024 x 1024 pixels. Chest-like and fry-like vibrations were observed, but could not be distinguished based on the input stimulation current to the recurrent laryngeal nerve. The subglottal pressure did distinguish the registers, as did an estimate of the thyroarytenoid muscle activity. Upon quantification of the three-dimensional motion, the method of Empirical Eigenfunctions was used to extract the underlying modes of vibration, and to investigate mechanisms of sustained oscillation. Results were compared with previous findings from excised larynx experiments and theoretical models.

Objectives: To develop a canine model of vocal fold scar and to evaluate its treatment with lamina propria replacement therapy using autologous cultured fibroblasts., Materials and Methods: Full thickness of the lamina propria layer in canine vocal folds was injured with a laser. Fibroblasts were cultured and expanded in the laboratory from a buccal mucosal biopsy. The scarred vocal folds were treated with 3 weekly injections of fourth, fifth, and sixth passage autologous fibroblasts. Mucosal waves and acoustic parameters were measured at baseline, after scarification, and several months after injection therapy. Histologic evaluation of the vocal folds for fibroblasts, collagen, elastin, reticulin, and hyaluronic acid was performed., Results: Nine beagle dogs were used, and 1 animal served as control. Vocal fold scarring resulted in absent or severely limited mucosal waves and significantly worse acoustic parameters. Significant improvements in mucosal waves and acoustic parameters were obtained after lamina propria replacement therapy. After therapy, mucosal waves became normal in 4 animals and near normal in the other 4. No statistical difference was found in mucosal waves between baseline and post-therapy. All animals tolerated therapy without complications. The treated vocal folds demonstrated an increased density of fibroblasts, collagen, and reticulin, a decreased density of elastin, and no change in hyaluronic acid., Conclusions and Significance: Therapeutic options for vocal fold scars are limited. Lamina propria replacement therapy in the form of autologous cultured fibroblasts improves mucosal pliability and returns normal or near normal mucosal waves in experimentally scarred vocal folds. This novel therapeutic modality may hold new promise for treating vocal fold scars.

The ideal injectable agent for vocal fold medialization is biocompatible, durable, sized to prevent phagocytosis and migration, and formulated for easy injection and does not adversely affect the viscoelastic properties of the vocal fold. We tested a cohesive implant of calcium hydroxylapatite (CaHA) particles in a gel carrier in an in vivo canine model of phonation. Six dogs underwent unilateral recurrent laryngeal nerve section and injection laryngoplasty of the paralyzed vocal fold with a CaHA implant. The six follow-up examinations were performed at 1, 2, 3, 6, 9, and 12 months, and the larynx and bilateral neck lymphatic system were harvested for histologic analysis. The CaHA implant adequately medialized the vocal fold to regain glottal closure. The mucosal waves remained unaltered from baseline. The implant remained soft in the larynx and did not migrate to the neck lymphatic system. A localized foreign body giant cell reaction was present on histologic evaluation, but not acute or other chronic inflammation. A size analysis revealed no resorption of the CaHA particles. A decrease in medialization was noted at all follow-up intervals related to resorption of the aqueous-based gel carrier. The CaHA implant appears to be relatively safe and suitable for injection laryngoplasty.

A canine model for recurrent respiratory papillomatosis (RRP) was developed with canine oral papillomavirus (COPV) inoculated into the buccal mucosa and supraglottic larynx of 5 beagles. The animals received systemic immunosuppression with daily oral prednisone at doses of 0, 1, 2, 3, and 4 mg/kg. Buccal papillomata developed at 6 weeks in all animals and regressed by 10 weeks in the animals that received 0 and 1 mg/kg. The other animals had continuous growth of their buccal papillomata for 26 weeks. The animal that received 2 mg/kg developed papillomata on the lingual surface of the epiglottis that continued to grow through 26 weeks. Systemic oral prednisone successfully maintained COPV-induced oral and laryngeal papillomata in beagles. Thus, COPV-induced oral and laryngeal papillomata that are prednisone-maintained may have utility as a model for RRP.

Purpose of Review: Glottic insufficiency secondary to vocal fold scarring, atrophy, or paresis remains a clinically challenging problem for the laryngologist. Numerous methods have been described in the treatment of glottic insufficiency, belying the complexity of the problem. Type I thyroplasty and injection of fat, fascia, and gelatin powder have been the mainstay of treatment to date, but the ability to restore a normal mucosal waveform to a damaged vocal fold remains an elusive goal., Recent Findings: Advances in the material and biomedical sciences have allowed the introduction of newer substances and techniques not only to medialize the vocal fold but also to help restore its viscoelastic properties as well. These substances include expanded polytetrafluoroethylene (ePTFE), collagen, cross-linked hyaluronic acid, micronized acellular human dermis calcium hydroxyapatite, and polydimethylsiloxane. ePTFE can be introduced through a window in the thyroid ala or placed intracordally, and the others can be injected either transorally or transcutaneously, allowing in-office placement under simple topical anesthesia., Summary: Although the ideal augmentation material and technique have yet to be devised, the laryngologist now has several options with which to address the problem of glottic insuffiency. Since the problem is complex and since it is possible that a customized solution may need to be devised on an individual basis, future laryngologists will need to be comfortable with the indications and applications that each material and technique will afford.