Jennifer L. Long

Epithelial differentiation of adipose‐derived stem cells for laryngeal tissue engineering

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.

Functional testing of a tissue-engineered vocal fold cover replacement

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.

EGFR expression in primary squamous cell carcinoma of the thyroid.

We present the case of a 57‐year‐old male with primary squamous cell carcinoma of the thyroid (PSCCT). Epidermal growth factor receptor (EGFR) staining was strongly positive. Pharmaceuticals targeting EGFR may provide an additional therapeutic option for this rare disease with extremely poor prognosis. Laryngoscope, 119:89–90, 2009

Microstructure Characterization of a Decellularized Vocal Fold Scaffold for Laryngeal Tissue Engineering

One potential treatment for vocal fold injury or neoplasia is to replace the entire vocal fold with a tissue‐engineered scaffold. This scaffold should ideally have similar mechanical properties and extracellular matrix composition as the native vocal fold. As one approach toward this goal, we decellularized human vocal folds and characterized their mechanical properties and extracellular matrix microstructure.

Dysphagia Characteristics in Zenker’s Diverticulum

Objectives To evaluate dysphagia characteristics in patients with Zenker’s diverticulum (ZD). Study Design Case series with chart review. Setting Outpatient tertiary care dysphagia clinic. Subjects and Methods All ZD cases surgically treated over a 6-year period were identified and reviewed for dysphagia history and dysphagia characteristics on initial presentation using fiber-optic endoscopic evaluation of swallowing (FEES). Dysphagia symptoms and swallowing abnormalities were compared across groups based on diverticulum size (small <1 cm, medium 1-3 cm, and large >3 cm). Results Forty-six patients underwent a total of 52 procedures during the study period. ZD size was available in 49 cases (6 small, 26 medium, 17 large). Regurgitation symptoms were less frequent in patients with small (17%) compared with medium (68%) or large diverticula (76%; P = .03). Postswallow hypopharyngeal reflux (PSHR) was less frequent in patients with small (17%) compared with medium (91%) and large diverticula (87%; P < .01). PSHR was present on all FEES available for patients who presented with a recurrent or residual ZD (n = 7). In all cases, PSHR resolved after successful treatment of ZD. Pharyngeal residue indicating possible weakness was present in 24% of all patients at initial presentation. Conclusions Preoperative assessment of dysphagia characteristics in ZD patients reveals that PSHR is predictive of a ZD larger than 1 cm and may be useful in surgical planning. PSHR is also helpful in identifying patients with recurrent or residual symptomatic ZD following surgical treatment. Pharyngeal weakness is present in a subset of ZD patients.

A Swallow Preservation Protocol Improves Function for Veterans Receiving Chemoradiation for Head and Neck Cancer

Objective Determine the efficacy of a swallow preservation protocol (SPP) on maintaining swallow function in patients undergoing chemoradiation (CRT) or radiation therapy alone (RT) for head and neck squamous cell carcinoma (HNSCC). Study design Retrospective case series. Setting Veterans Affairs medical center. Subjects and Methods Patients treated with CRT or RT for HNSCC between February 2006 and November 2013 were studied. Those enrolled in the SPP participated in swallowing, jaw, and tongue exercises during cancer therapy. The comparator group received no swallowing intervention during CRT. A previously described functional outcome swallowing scale (FOSS; 0 = no symptoms and 5 = nonoral feeding for all nutrition) was used to quantify dysphagia prior to and at the completion of cancer therapy, and an analysis was performed to compare swallowing function. Results Forty-one (all male; mean age, 66 years) and 66 patients (all male; mean age, 61 years) were included in the SPP and comparator groups, respectively. In the SPP group, mean pre- and posttreatment FOSS scores were 2.2 and 2.2, respectively, while the corresponding scores in the comparator group were 1.8 and 2.7, respectively, with posttreatment FOSS scores being significantly worse than pretreatment FOSS scores in the comparator group only. Conclusion Patients enrolled in the SPP demonstrated preserved swallowing function over the course of cancer treatment compared with a comparator group. This confirms the importance of early evaluation and intervention for dysphagia prior to and during CRT or RT alone.

Tissue-Engineered Vocal Fold Mucosa Implantation in Rabbits

Objective To assess phonatory function and wound healing of a tissue-engineered vocal fold mucosa (TE-VFM) in rabbits. An “artificial” vocal fold would be valuable for reconstructing refractory scars and resection defects, particularly one that uses readily available autologous cells and scaffold. This work implants a candidate TE-VFM after resecting native epithelium and lamina propria in rabbits. Study Design Prospective animal study. Setting Research laboratory. Subjects and Methods Rabbit adipose-derived stem cells were isolated and cultured in three-dimensional fibrin scaffolds to form TE-VFM. Eight rabbits underwent laryngofissure, unilateral European Laryngologic Society type 2 cordectomy, and immediate reconstruction with TE-VFM. After 4 weeks, larynges were excised, phonated, and examined by histology. Results Uniform TE-VFM implants were created, with rabbit mesenchymal cells populated throughout fibrin hydrogels. Rabbits recovered uneventfully after implantation. Phonation was achieved in all, with mucosal waves evident at the implant site. Histology after 4 weeks showed resorbed fibrin matrix, continuous epithelium, and mildly increased collagen relative to contralateral unoperated vocal folds. Elastic fiber appearance was highly variable. Inflammatory cell infiltrate was limited to animals receiving sex-mismatched implants. Conclusion TE-VFMs were successfully implanted into 8 rabbits, with minor evidence of scar formation and immune reaction. Vibration was preserved 4 weeks after resecting and reconstructing the complete vocal fold cover layer. Further studies will investigate the mechanism and durability of improvement. TE-VFM with autologous cells is a promising new approach for vocal fold reconstruction.

Effects of vocal fold epithelium removal on vibration in an excised human larynx model

This study investigated the impact of selective epithelial injury on phonation in an excised human larynx apparatus. With intact epithelium, the vocal folds exhibited a symmetrical vibration pattern with complete glottal closure during vibration. The epithelium was then enzymatically removed from one, then both vocal folds, which led to left-right asymmetric vibration and a decreased closed quotient. Although the mechanisms underlying these vibratory changes are unclear, these results demonstrate that some component of an intact surface layer may play an important role in achieving normal symmetric vibration and glottal closure.

Functional Reinnervation of Vocal Folds After Selective Laryngeal Adductor Denervation-Reinnervation Surgery for Spasmodic Dysphonia

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 patients 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.

Chapter 10.1 - Functions of the larynx and production of sounds

Abstract Vocalization in most mammalian species occurs in the larynx. This organ has developed a degree of complexity commensurate with its role in communication and as the source of self-expression through language in humans. However, the larynx also performs more primitive actions relating to respiration and swallowing. Laryngeal functions and functional anatomy are considered in this section. The myoelastic aerodynamic theory, describing how sound is produced by the vocal folds, is outlined. Illustrative examples of laryngeal pathology and laryngeal control mechanisms are discussed.