The treatment of laryngotracheal stenosis remains a challenge. Our previous studies focused on basic research and the clinical applications of an artificial trachea. In this study we focused on the challenge posed by the fact that a prefabricated artificial trachea cannot be utilized for pediatric airways since the tracheal frame needs to expand as the child develops. Induced pluripotent stem (iPS) cells were first generated in 2006. These cells are capable of unlimited symmetrical self-renewal, thus providing an unlimited cell source for tissue-engineering applications. In this report, iPS cells were cultured in a three-dimensional (3D) scaffold in Chondrocyte Differentiation Medium (CDM). After cultivation, differentiation into chondrocytes was examined. The ratio of undifferentiated cells was analyzed by flow cytometry. The 3D scaffolds were implanted into tracheal defects in 24 nude rats. Differentiation into chondrocytes in vitro was confirmed histologically, phenotypically and genetically. Flow cytometric analysis demonstrated that the population of undifferentiated cells had decreased. Cartilage tissue was observed in the regenerated tracheal wall. The expression of cartilage-specific protein was also demonstrated in vivo. The presence of the green fluorescent protein (GFP) gene derived from iPS cells was confirmed in samples of cartilage tissue by the combination of Laser Microdissection (LMD) and Polymerase Chain Reaction (PCR) techniches. Our results suggest that iPS cells could be a new cell source for the regeneration of the trachea.
It is impossible to avoid the deterioration in physical function that accompanies aging. We believe that the aim of anti-aging research is to examine ways to maximize physical function within the human lifespan, rather than to investigate immortality. The first author conducted research at the Connor laboratory (University of Wisconsin) from 2002 to 2004. The Connor lab investigates histological and physiological changes that accompany aging in the genioglossus and intra-laryngeal muscles, which are important for deglutition and vocalization, respectively. That is, the lab investigates alterations of phonation and deglutition that occur with aging. The first author researched the effects of controlled release of basic fibroblast growth factor with autologous fascia implantation in unilateral laryngeal paralysis. It was hypothesized that this method would induce regeneration of damaged tissue associated with paralysis by providing a scaffold, cells, and growth factors. In experiments using rats, the glottal gap decreased, volume of the paralyzed glottal area increased, and atrophy of the thyroarytenoid muscle improved. These findings suggest that the method may present an attractive option for treating unilateral laryngeal paralysis.
The purpose of this study was to compare the functional biomechanical properties of some injectable phonosurgical biomaterials commonly used for vocal fold augmentation. Linear viscoelastic shear properties of cross-linked hyaluronic acid (HA; Juvederm®), micronized AlloDerm (Cymetra®), 3% bovine collagen (Atelocollagen), and calcium hydroxylapatite (CaHA; Radiesse®) were determined 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 (η‘) were made up to 250 Hz 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 ANOVA. There were statistically significant differences in the magnitudes of G‘ and η‘ among the phonosurgical materials and the normal human vocal fold cover (p<0.01), whereas there was no significant difference (p<0.05) in pairwise comparisons among all materials and the normal vocal fold cover. The rheometric properties of Juvederm and Atelocollagen were the closest match to those of the vocal fold cover. These findings suggest that none of the tested injectable biomaterials are ideal implants for facilitating the functional vibratory performance of the vocal fold cover. Future studies for the development of materials with optimal viscoelastic properties are warranted.
Organ and function preservation strategies for laryngeal and hypopharyngeal cancer consist of chemoradiation, open partial laryngopharyngectomy and transoral surgery. Among them, transoral surgery is gaining attention for its reduced invasiveness, rapid recovery and greater postoperative function. To perform a transoral en bloc tumor resection, we built a new surgical system: transoral videolaryngoscopic surgery (TOVS). In this surgical setting, a distending laryngoscope and a high definition laryngeal rigid endoscope were used to display a wide view on the monitor. The tumor was resected by using fine laparoscopic surgical instruments such as forceps, scissors and needle electrocautery. To perform transoral surgery safely, the first step is to understand the surgical anatomy from the inside of the laryngopharyngeal lumen. From the experience of cadaver dissection and many case series, transoral surgical anatomy was described with a schema.
Vocal fold augmentation with autologous fat has been widely applied for management of glottic insufficiency, including vocal fold paresis, vocal fold atrophy, and sulcus vocalis. We describe the techniques in vocal fold augmentation with autologous fat. 1. Tips and actual procedure 1) Fat Tissue: Buccal Fat Pad 2) Injection sites : With cases of unilateral vocal fold paralysis, the needle should be stuck from posterior at the middle of vocal fold membranous region and the essential point is to increase the volume of the entire vocal fold muscle. In sulcus vocalis cases, volume is first increased in the shallow part of the muscle layer. The needle is then withdrawn a little and injection proceeds into the lamina propria mucosa. 3) Tool: An electric injector and a 19-G needle, 28cm-long. 2. Evaluation after injection Autologous fat injection is a relatively safe rehabilitation technique for treating deficiencies in glottal closure. However, excessive use of autologous fat injection can impair voice function. In cases in which there is no improvement in phonation following fat injection, it is important to assess the presence of fat tissues using CT and to determine its effects on wave motion during phonation.
The mechanism of vocal cord motion while stuttering remains unclear. A study by Conture et al. (1977) presented 100% glottic closures with only a sample of six stuttering blocks. A larger study sample was required. This study examined 34 stuttering blocks through flexible fiberscopic imaging and mesurements by speech phonogram, airflows and voice waveforms. The percentage of glottic closure and glottic opening were about 50% and 50% respectively. Vocal cord positions varied from individual to individual while block were manifested. Our findings indicate the cause of stuttering in not to be larynx but rather in the brain.
Conventional arytenoid adduction is often associated with a risk of perforating the piriform sinus, bleeding or edema of the larynx following airway obstruction. We designed a simple and less invasive method, Endoscopic-assisted Arytenoid Adduction Surgery (EAAS), for unilateral vocal fold paralysis (UVFP), in which we employ a looped traction nylon thread under laryngeal endoscopic guidance. We reported that our phonation analysis date thus far has indicated the efficacy of EAAS and that no major complications such as airway obstruction have occurred. As it is truly important to evaluate how patients personally perceive their benefits, we now evaluate them using an objective index such as Japanese versions of voice handicap index (VHI) and singing voice handicap index (SVHI). We retrospectively examined 14 patients with UVFP for the following measurements: maximum phonation time (MPT), mean air flow rate (MFR), and three acoustic analysis parameters which were measured before and after EAAS. Ten of them answered the VHI and SVHI questionnaires. Postoperatively, VHI score significantly improved from their preoperative values, but SVHI have not done so. Statistical correlations were seen between VHI and MPT or MFR. These results suggest the validity of EAAS from the perspective of the voice handicap of phonation disorder.
Patients with Japanese cedar pollinosis (JCP) often complain of cough and throat symptoms. We have extensively investigated the prevalence and characteristics of coughing and other symptoms in adults and children with JCP, through questionnaires in the pollen season from 2009 to 2011. According to the questionnaire, 29-44% of adults and 31-48% of children complained of coughing. There was neither significant differences in the prevalence of coughing between adults and children, and nor among three season. The severity of the coughing in each patient was almost mild or moderate. Particularly in children, productive cough was significantly more prominent, and throat symptoms were less found than those in adults. In 2009, total nasal symptom score was significantly higher in coughing patients rather than in ones without a cough. However, there were no correlations between coughing and throat symptoms with either adults or children in each year. These results may indicate that coughing in patients with JCP could be attributed to not only laryngeal allergy but also direct influence of nose inflammation. The difference in features of coughing between adults and children suggests the varied pathology in coughing by age.
We performed clinical examination about the usefulness of the superselective intra-arterial chemotherapy for laryngeal cancer. The study group was composed 12 cases of glottic cancer and 9 with supraglottic cancer. Chemotherapy was performed through a catheter inserted into the superior thyroid artery via the forearm artery. The dose of cisplatin was 100mg/body per infusion session. A radiotherapy doses of 60Gy was performed in all cases. All cases of glottic cancer exhibited a complete response (CR); however, there was local recurrence in two cases. While the survival rate was 100%, the laryngeal preservation rate was 83%.Eight cases of supraglottis cancer demonstrated CR, but one case had partial response (PR). Cervical lymph node recurrence was observed in two cases. The survival rate and the laryngeal preservation rate were 88%. Grade3 mucositis was observed in 12 cases. Superselective intra-arterial chemotherapy for laryngeal cancer was found to be one of the more effective treatments in larynx preservation.