Viscoelastic properties of human aryepiglottic fold and ventricular fold tissues at phonatory frequencies.

OBJECTIVE: The purpose of this study was to quantify the viscoelastic shear properties of the human ventricular fold (or false vocal fold) mucosa and aryepiglottic fold mucosa at frequencies of phonation. METHODS: Linear viscoelastic shear properties of the mucosa of false vocal fold and aryepiglottic fold specimens from seven cadaveric subjects were determined as functions of frequency (5-250 Hz) and compared to those of the true vocal fold cover. Measurements of elastic shear modulus (G') and dynamic viscosity (η') were made with a controlled-strain simple-shear rheometer. Linear least-squares regression was conducted to curve-fit log G' and log η' versus log frequency, and statistical analysis was performed with one-way analysis of variance. RESULTS: All specimens showed similar frequency dependence of the viscoelastic functions G' and η', with G' gradually increasing with frequency and η' monotonically decreasing with frequency. The magnitudes of G' and η' of the false fold mucosa were generally higher than those of the aryepiglottic fold mucosa and true vocal fold cover, but there were no significant differences in G' and η' among the false fold, aryepiglottic fold, and true vocal fold. CONCLUSION: The false vocal fold and aryepiglottic fold mucosa showed similar frequency dependence and a similar range of tissue viscoelastic behavior as the true vocal fold. These preliminary findings suggested that such tissues could become candidates for the replacement of the true vocal fold lamina propria in patients with significant tissue loss and deficiencies, for those requiring laryngeal reconstruction following partial laryngectomy or airway reconstruction. LEVEL OF EVIDENCE: NA. Laryngoscope, E296-E301, 2018.

Single institutional analysis of trends over 45 years in etiology of vocal fold paralysis.

OBJECTIVE: It is important to assess the causes of vocal fold paralysis. Many studies have reported causes of paralysis, but few reports have shown changes in longitudinal etiology in a single institution. METHODS: We investigated the medical records of 797 patients with vocal fold paralysis from 1990 to 2005 at the voice and bronchoesophageal outpatient clinics at the University of Tokyo Hospital. We evaluated the etiology of paralysis, and compared our results with a previous study by Hirose in our clinic from 1961 to 1989 to assess changes in etiology. RESULTS: The postoperative group comprised 466 patients (58.5%), while the non-surgical group comprised 331 (41.5%) patients. In the postoperative group, the most common cause of paralysis was thyroid surgery (106 cases), and other common causes were surgery for aortic aneurysm (61 cases) and tracheal intubation (58 cases). In the non-surgical group, idiopathic paralysis (134 cases) was the most common cause. Other common causes were lung cancer (34 cases) and cerebrovascular disease (24 cases). In a previous study from our clinic, the rate of postoperative paralysis was 43.5%. In the current analysis, the percentage of postoperative patients has increased remarkably compared with that of the previous report while the rate of idiopathic paralysis, has decreased by half. CONCLUSION: The increase in postoperative cases of paralysis may be caused by the increasing frequency of operations for many diseases, due to the progress of medical techniques in recent years. The decrease in idiopathic cases may be related to the advances of diagnostic devices such as CT and MRI.

Injection of human mesenchymal stem cells improves healing of vocal folds after scar excision--a xenograft analysis.

OBJECTIVES: Using a xenograft model the aim was to analyze if injection of human mesenchymal stem cells (hMSC) into the rabbit vocal fold (VF), after excision of an established scar, can improve the functional healing of the VF. STUDY DESIGN: Prospective design with an experimental xenograft model. METHODS: The VFs of 12 New Zealand rabbits were injured by a bilateral localized resection. After 9 weeks the scar after the resection was excised and hMSC were injected into the VFs. After another 10 weeks 10 VFs were dissected and stained for histology. Lamina propria thickness and relative content of collagen type I were measured. Viscoelasticity of 14 VFs at phonatory frequencies was quantified by a simple-shear rheometer. The hMSC survival was determined using a human DNA specific reference probe, that is, FISH analysis. RESULTS: The viscoelastic measurements, that is, dynamic viscosity and elastic shear modulus for the hMSC-treated VFs, were found to be similar to those of normal controls and were significantly lower than those of untreated controls (P < .05). A significant reduction in lamina propria thickness was also shown for the hMSC treated VFs compared with the untreated VFs (P < .05). This histologic finding corresponded with the viscoelastic results. No hMSC survived 10 weeks after the injection. CONCLUSIONS: Human mesenchymal stem cells injected into the rabbit VF following the excision of a chronic scar, were found to enhance the functional healing of the VF with reduced lamina propria thickness and restored viscoelastic shear properties.

Local vascularized flaps for augmentation of Reinke's space.

OBJECTIVES/HYPOTHESIS: The purpose of this study is to describe and test a novel surgical strategy for augmentation of Reinke's space using vascularized flaps: a thyroid ala perichondrium flap (TAP) and a composite thyroid ala perichondrium flap (CTAP) from the anterior larynx. We hypothesized that these specially designed vascularized flaps would remain viable once inset into the lamina propria, and that they would not disrupt rheologic, biomechanical, and histologic properties of the native vocal fold. STUDY DESIGN: Experimental. In vivo canine model. METHODS: The length and volume of test flaps harvested in six adult human cadaveric larynges were analyzed to determine suitability for use in augmentation in the lamina propria. Also, 12 beagles randomly underwent unilateral placement of either TAP or CTAP, which were designed in accordance with the human adult cadaveric experiments. Flap perfusion was measured before and after harvest with laser Doppler. After 1 month, the beagles were humanely sacrificed and their larynges subjected to aerodynamic and acoustic evaluation using an excised larynx apparatus. The vocal fold lamina propria of four larynges--two TAP and two CTAP--underwent rheologic evaluation using a simple-shear rheometer. The remaining eight larynges underwent quantitative histologic and immunohistochemical evaluation. The survival and complication (swallowing, airway, local wound) rates of all dogs were noted. RESULTS: Initial studies with adult human cadaveric larynges established that TAP and CTAP possessed length and volume greater than native lamina propria. In the canine experiments, the perfusion change in the flaps was similar between flap groups. The damping ratio (ζ), dynamic viscosity (η'), elastic shear modulus (G'), and viscous shear modulus (G″) of treated and untreated native vocal folds were not statistically different. The glottic function measures of vocal efficiency, laryngeal resistance, jitter, shimmer, and harmonics-to-noise ratio (HNR) of treated and normal larynges were not statistically different. Similarly, the values for collagen, elastin, and glycosaminoglycans (GAGs) in treated and untreated vocal folds were not statistically different. Also, neither neochrondrogenesis nor neoosteogenesis was detected in any treated vocal fold. The values for vascular and cellular proliferation in treated and untreated vocal folds were not statistically different. All test dogs survived and had no complications related to swallowing, airway distress, or the local wound. CONCLUSIONS: The test flaps described and tested in this study appear to have conceptually attractive features for augmentation of Reinke's space. When placed in an in vivo setting TAP and CTAP did not reveal unfavorable vascular, rheologic, aerodynamic, acoustic, or histologic characteristics. There was no unanticipated morbidity or mortality to the test animals. Long-term viability of these flaps is unknown. TAP and CTAP may open novel pathways for correction of glottic defects and may offer crossover opportunities with tissue engineering techniques.

Rheometric properties of canine vocal fold tissues: variation with anatomic location.

OBJECTIVE: To evaluate the in vitro rheometric properties of the canine vocal fold lamina propria and muscle at phonatory frequencies, and their changes with anatomic location. METHODS: Six canine larynges were harvested immediately postmortem. Viscoelastic shear properties of anterior, middle, and posterior portions of the vocal fold cover (lamina propria) as well as those of the medial thyroarytenoid (TA) muscle (vocalis muscle) were quantified by a linear, controlled-strain simple-shear rheometer. Measurements of elastic shear modulus (G') and dynamic viscosity (η') of the specimens were conducted with small-amplitude sinusoidal shear deformation over a frequency range of 1-250Hz. RESULTS: All specimens showed similar frequency dependence of the viscoelastic functions, with G' gradually increasing with frequency and η' decreasing with frequency monotonically. G' and η' of the canine vocalis muscle were significantly higher than those of the canine vocal fold cover, and η' of the canine vocal fold cover was significantly higher than that of the human vocal fold cover. There were no significant differences in G' and in η' between different portions of the canine vocal fold cover. CONCLUSION: These preliminary data based on the canine model suggested that the vocalis muscle, while in a relaxed state in vitro, is significantly stiffer and more viscous than the vocal fold cover during vibration at phonatory frequencies. For large-amplitude vocal fold vibration involving the medial portion of the TA muscle, such distinct differences in viscoelastic properties of different layers of the vocal fold should be taken into account in multi-layered biomechanical models of phonation.

Arytenoid adduction for correcting vocal fold asymmetry: high-speed imaging.

OBJECTIVES: We hypothesized that high-speed digital imaging provides a quantitative method to evaluate the effect of arytenoid adduction for the correction of asymmetric and irregular vocal fold vibration in unilateral vocal fold paralysis. METHODS: Six subjects with unilateral vocal fold paralysis participated in the study (4 male, 2 female; mean [-SD] age, 52.5 +/- 21.3 years). Videokymographic and laryngotopographic methods for image analysis were performed for high-speed recordings of vocal fold vibration for visualizing the glottal vibratory patterns, and for quantifying the frequency of vibration of each vocal fold, respectively. Comparisons of the paralyzed and the normal vocal folds were made before and after arytenoid adduction. RESULTS: Analysis of the laryngotopographs revealed 2 distinct frequencies of vibration for the paralyzed and the contralateral vocal folds for all subjects before surgery. After arytenoid adduction, the vibration frequencies became identical or nearly identical in all subjects. CONCLUSIONS: Asymmetric vibration in vocal fold paralysis was exemplified by differences in vibration frequency between the vocal folds. The present data showed that after arytenoid adduction the vibration frequencies and the vibratory patterns of the contralateral vocal folds approached symmetry. This surgical procedure could improve the functional symmetry of the larynx for phonation.

Collagen injection for correcting vocal fold asymmetry: high-speed imaging.

OBJECTIVES: We hypothesized that high-speed digital imaging with videokymographic and laryngotopographic analysis would provide a quantitative method to evaluate the effect of collagen injection for the correction of asymmetric and irregular vocal fold vibration in unilateral vocal fold paralysis. METHODS: Videokymographic and laryngotopographic analysis was performed for high-speed digital recordings of vocal fold vibration for visualizing the glottal vibratory patterns, and for quantifying the frequency of vibration of each vocal fold, respectively, including comparisons between the paralyzed and normal vocal folds before and after surgery. This included prospective observations of 11 subjects with unilateral vocal fold paralysis (4 male, 7 female; mean +/- SD age, 67.1 +/- 12.0 years) using high-speed digital image analysis before and after collagen injection. RESULTS: Analysis of the laryngotopographs revealed 2 distinct frequencies of vibration for the paralyzed and contralateral vocal folds for 8 of the 11 subjects before surgery. After collagen injection, the vibration frequencies became identical, despite asymmetric vibration amplitudes. Asymmetric vibration amplitudes were also observed in the other 3 subjects before surgery, but the amplitudes became symmetric after collagen injection, despite a persistent phase shift. CONCLUSIONS: Asymmetric vibration in vocal fold paralysis was exemplified by differences in vibration frequency and amplitude between the vocal folds. The present study showed that after collagen injection, these aspects of vibratory patterns improved toward symmetry. This surgical procedure could improve the functional symmetry of the larynx for phonation.

Viscoelastic properties of phonosurgical biomaterials at phonatory frequencies.

OBJECTIVES/HYPOTHESIS: The purpose of this study was to examine the functional biomechanical properties of several injectable biomaterials currently or potentially used for vocal fold augmentation. STUDY DESIGN: Rheometric investigation of phonosurgical materials in vitro. METHODS: Linear viscoelastic shear properties of 3% bovine collagen (atelocollagen), micronized AlloDerm (Cymetra; LifeCell Corp., Branchburg, NJ), calcium hydroxylapatite (CaHA) (Radiesse; BioForm Medical, San Mateo, CA), and 2.4% cross-linked hyaluronic acid (HA) gel (Juvéderm; Allergan, Inc., Irvine, CA) were quantified as functions of frequency covering the phonatory range, and compared to those of the human vocal fold cover. Measurements of elastic shear modulus (G') and dynamic viscosity (eta') were made at up to 250 Hz with a controlled-strain simple-shear rheometer. Linear least-squares regression was conducted to curve-fit log G' and log eta' versus log frequency, and statistical analysis was performed with one-way analysis of variance. RESULTS: Radiesse and Cymetra were found to be the stiffest and the most viscous materials, followed by Juvéderm and atelocollagen. There were significant differences in the magnitudes of G' and eta' among the phonosurgical materials and the normal human vocal fold cover (p < .001), whereas there was no significant difference in the frequency dependence of G' and eta' among the materials. Post hoc Tukey tests revealed significant differences (p < .05) in pairwise comparisons of the magnitudes of G' and eta' among all materials and the vocal fold cover. CONCLUSIONS: These findings suggested that although these biomaterials may be injected lateral to the lamina propria for the treatment of glottic insufficiency, none of them are rheologically optimal for the functional reconstruction of the vocal fold lamina propria.

High-speed digital imaging of the neoglottis after supracricoid laryngectomy with cricohyoidoepiglottopexy.

OBJECTIVE: To determine the utility of high-speed digital imaging (HSDI) in evaluating vocal kinetics of the neoglottis after supracricoid laryngectomy with cricohyoidoepiglottopexy (SCL-CHEP). STUDY DESIGN: Case series. SETTING: The University of Tokyo Hospital. SUBJECTS AND METHODS: High-speed digital recordings of laryngeal images were obtained from six patients after SCL-CHEP to clarify the vocal kinetics of the postoperative neoglottis. Simultaneous recording of electroglottograms (EGGs) were obtained and multiline kymograms were generated on the basis of the recorded images. The distribution of frequency, amplitude, and phase in the neoglottis were visualized by using gradients of colors superimposed onto the glottal and supraglottal areas of laryngeal images to produce laryngeal topograms. Furthermore, waveforms of estimated laryngeal sound source (ELSS) were obtained on the basis of glottal inverse filtering of the vocal signal to reflect vibratory motions in the neoglottis. The vibratory part of the neoglottis was determined as a possible sound source when the frequencies of the ELSS, EGG, and laryngeal topograms, as well as the waveforms of ELSS, EGG, and kymograms, were consistent with each other. RESULTS: Spaces between the arytenoid(s) and epiglottis (5 patients) or pyriform sinus mucosa (1 patient) were estimated as the major source of sound during postoperative vocalization. The possible sound source could be determined by HSDI, even in the neoglottis, with more than one vibratory position. CONCLUSION: HSDI could be useful for evaluating the vocal kinetics of the neoglottis after SCL-CHEP.

Clinical analysis of presbylarynx--vocal fold atrophy in elderly individuals.

OBJECTIVE: The proportion of elderly Japanese is increasing significantly and aging society greatly influences the medical services. The number of elderly patients who visited out Voice Outpatient Clinic has been increasing in recent years. The aim of the present study was to analyze the trend in the number of patients with aging-related vocal fold atrophy, and to assess the characteristics of senile change of vocal function. METHODS: A retrospective review of the 1999-2005 medical records of patients aged > or =65 years was conducted, and patients with presbylarynx were analyzed. We evaluated age, sex, occupation, maximal phonation time (MPT), and mean airflow rate (MFR) during comfortable phonation to assess the physiological characteristics of senile change of vocal function. We compared MFR of presbylarynx with those of normal elderly person. RESULTS: The number of patients aged > or =65 who visited our clinic in the 7-year study period was 361, and 72 (20%) were diagnosed with vocal fold atrophy. They included 47 (65%) men and 25 (35%) women, with a mean age of 71 years (range, 65-89). Among these patients, 27 (38%) were still employed at the time of consultation, while 17 (24%) were retired, at least 26 jobs required voice skills; and 15 patients (21%) were involved in singing and recitation of poems. MPT correlated negatively with age, while MFR correlated positively with age. CONCLUSION: The number of elderly patient with vocal fold atrophy increased gradually almost every year. The male patients account for 65%. Thirty-three percent of patient of the present study with presbylarynx were still in the workforce. MFR correlated positively and significantly with age. MFR was higher in presbylarynx than normal elderly person.

A case of nasal natural killer/T lymphoma revealed by repeated deep neck abscess.

A diagnosis of natural killer (NK)/T-cell lymphoma was clarified after repeated deep neck abscess in a 63-year-old man. The absolute number of lymphocytes was mildly decreased. Lymphopenia induced by latent malignant lymphoma in this case likely caused the immunodeficiency, which induced repeated infection in the head and neck region. We conclude that it is always necessary to consider diseases caused by immunodeficiency conditions, such as malignant lymphoma, into consideration in a case of repeated deep neck abscess.

Analyses of risk factors for postoperative airway compromise following arytenoid adduction.

CONCLUSION: This study suggests that placing no drainage tube and postoperative bleeding are risk factors for postoperative airway compromise (PAC) following arytenoid adduction (AA). OBJECTIVES: In this study, we aimed to elucidate the risk factors for PAC following AA. PATIENTS AND METHODS: The data for 184 consecutive patients who underwent AA were analyzed retrospectively. Univariate and forward stepwise multivariate logistic regression analyses were performed. RESULTS: Placing no drainage tube was a significant risk factor for PAC as determined by both univariate and multivariate analyses. Postoperative bleeding was a significant risk factor for severe airway compromise requiring emergency airway treatment.

Collagen injection as a supplement to arytenoid adduction for vocal fold paralysis.

OBJECTIVES: Dysphonia associated with vocal fold paralysis can persist even after successful medialization procedures, including arytenoid adduction. It is hypothesized that laryngeal collagen injection could improve phonation following arytenoid adduction in selected patients. Our objective was to evaluate how collagen injection could result in measurable improvements in vocal function and voice quality. METHODS: Forty patients with unilateral vocal fold paralysis who had undergone arytenoid adduction underwent transoral injection of non-cross-linked bovine dermal collagen by means of indirect laryngoscopy and a curved injection device. A control group of 40 patients underwent arytenoid adduction but not collagen injection. The patients' voice quality was assessed perceptually with the GRBAS scale, and vocal function was assessed by acoustic and aerodynamic measures (maximum phonation time and transglottal DC flow). The relative glottal area was also assessed by videostroboscopy. RESULTS: Significant improvements in vocal function and voice quality were observed with collagen injection for those patients who did not achieve satisfactory glottal competence with arytenoid adduction alone. Glottal area measurements revealed that glottic insufficiency was significantly reduced after arytenoid adduction as well as after collagen injection. CONCLUSIONS: The findings suggest that collagen injection could be an effective supplementary treatment for improving voice following arytenoid adduction. It has the advantage of being a minimally invasive outpatient office procedure. The long-term efficacy of the procedure should be explored.

Clinical experience with collagen injection of the vocal fold: a study of 155 patients.

OBJECTIVE: This study evaluated the results of laryngeal collagen injection. STUDY DESIGN: Retrospective study of patients who had undergone laryngeal collagen injection. MATERIALS AND METHODS: A retrospective review of 275 patients treated with collagen injection and a review of the relevant literature on the results of treatment were presented. Follow-up studies were performed for at least 3 months on 155 patients. The patients' voice quality was assessed by perceptual voice analysis using the GRBAS scale, and their vocal function was assessed by acoustic and aerodynamic measures (maximal phonation time and mean flow rate). Assessments were performed before and after collagen injection. RESULTS: Mean objective measures and clinician's perceptual ratings demonstrated measurable improvement in vocal function and voice quality after collagen injection. There were no major complications and no hypersensitivity reactions. CONCLUSION: As an outpatient office procedure, collagen injection offers a simple, efficient and effective treatment for dysphonia. Various aspects of the procedure for anesthesia, injection techniques, and patient selection are discussed.

Three cases of ortho-phthalaldehyde-induced anaphylaxis after laryngoscopy: detection of specific IgE in serum.

BACKGROUND: Ortho-phthalaldehyde (OPA) has recently been used as a disinfectant for various medical apparatuses. OPA is not generally recognized as a potential allergen. CASE SUMMARY: Subsequent to our recent report describing a patient presenting with OPA-induced anaphylaxis following laryngoscopy, we experienced two more such cases. In all three cases, the basophil histamine release test was useful for identifying the allergen as OPA. OPA-specific IgE was successfully detected in the serum of the patients by ELISA. DISCUSSION: Physicians and co-medical workers need to be aware of potential allergens to which patients may be exposed during routine medical procedures.

Tonsillar cyst of the false vocal cord.

OBJECTIVES/HYPOTHESIS: To report, for the first time, tonsillar cyst of the false vocal cord. STUDY DESIGN: Case report. METHODS: Case presentation and literature review. RESULTS: A 74-year-old woman with a mass in the false vocal cord presented with hoarseness. Histopathological examination revealed tonsillar cyst. Marsupialization via microlaryngeal approach failed. Finally the cyst was resected successfully through a lateral cervical approach with concomitant tracheotomy. CONCLUSIONS: This is the first report of tonsillar cyst in the false vocal cord in English literature. The cyst was finally resected through the lateral cervical approach with success.

Parathyroid adenoma causing spontaneous cervical hematoma: a case report.

A case of parathyroid adenoma causing a spontaneous cervical hematoma is reported. A 55-year-old woman presented with painful swallowing, dysphagia, and dyspnea. Primary hyperparathyroidism and a parathyroid tumor on the left side of the neck had been found 2 years earlier. Fiberoptic laryngoscopy and computed tomography (CT) showed a narrowing of the airway as a result of a retropharyngeal hematoma, and tracheostomy was carried out. Parathyroidectomy was performed 5 months after the absorption of the hematoma, with no complications. A pathological diagnosis revealed a parathyroid adenoma with hemosiderin deposition and fibrosis. Serum calcium and intact parathormone levels normalized postoperatively. Although a spontaneous cervical hematoma resulting from parathyroid tumors rarely occurs, it may lead to an airway compromise. Physicians should be aware of this if such tumors are managed conservatively without surgery.

Geometrical deformation of vocal fold tissues induced by formalin fixation.

OBJECTIVES/HYPOTHESIS: Many existing studies of vocal fold geometry are based on anatomical measurements made on histologically fixed laryngeal tissues using formalin. However, the validity of these geometric data is questionable because of the potentially significant tissue deformation associated with formalin fixation, particularly tissue shrinkage. Previous experiments have shown that valid geometric data may be obtained on vocal fold tissue samples quickly frozen with liquid nitrogen. Based on this finding, the present study attempted to quantify the geometric deformation of formalin-fixed vocal fold tissues with respect to quick-frozen tissues. METHODS: Six freshly harvested canine larynges were quickly frozen with liquid nitrogen and sectioned at the mid-membranous coronal plane. Each larynx was thawed and divided into halves along the midsagittal plane, one of which was not fixed; the other was fixed with formalin, from which histological tissue sections were also prepared. Measurements of vocal fold geometry were made on digital images of mid-membranous coronal sections of the tissue samples, based on linear dimensions of vocal fold depth and thickness defined functionally for biomechanical applications. RESULTS: Significant shrinkage of the vocal fold (particularly the vocal fold body) and considerable distortion of the vocal fold contour (particularly at the free edge) were observed for the formalin-fixed samples and the histological sections in comparison with the unfixed samples. CONCLUSIONS: Results of the present study suggested that significant geometric artifacts are induced by conventional histological fixation of laryngeal tissues using formalin. These artifacts should be carefully considered for interpreting any vocal fold geometric data obtained through formalin fixation.