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Objective This study aimed to validate new staging of Japanese patients with human papillomavirus-mediated oropharyngeal cancer (HPV+-OPC) and the effectiveness of transoral surgery.Methods Fifty-three patients with HPV+-OPC were classified according to the seventh and eighth editions of the American Joint Committee on Cancer (AJCC) staging, along with assessment of prognosis, smoking and alcohol status, and treatment outcome. Transoral videolaryngoscopic surgery (TOVS) was performed as transoral surgery.Results The 5-year overall survival (OS) rate was 77.3% in all patients. Five-year OS rates of seventh edition staging were as follows: II, 100%; III, 100%; IVa, 75.9%; and IVb and IVc, 0%. Five-year OS rates of the eighth edition clinical staging were as follows: I, 89.3%; II, 88.9%; III, 46.3%; and IV, 0%. In non-smoking and smoking patients with HPV+-OPC, the 5-year OS rates were 90.9% and 70.7%, respectively. TOVS was used for treating 20 smokers with HPV+-OPC (5-year OS: 85.7%), while 12 were treated with chemoradiotherapy (5-year OS: 75.0%).Conclusions The eighth edition of the AJCC determines the prognosis of HPV+-OPC more accurately than the seventh edition in clinical staging. Smokers with HPV+-OPC have a poor prognosis, but TOVS might improve the prognosis.

Descending necrotizing mediastinitis (DNM) is a serious infection that spreads from the neck, oral cavity and pharynx to the mediastinum.

Objectives:We assessed the outcome of en bloc transoral resection of supraglottic and hypopharyngeal cancer using a distending laryngoscope with rigid videoendoscopic and laparoscopic surgical instruments.Methods:We enrolled 30 patients with T1, T2, or selected T3 supraglottic and hypopharyngeal cancer in the study; 9 patients had undergone radiotherapy. Neck dissections were performed for node-positive patients. Postoperative radiotherapy was administered to patients with multiple lymph node metastases or positive surgical margins.Results:This surgical environment provided a wide view of the operative field, facilitating bimanual manipulation of laparoscopic surgical instruments, and enabled us to perform en bloc transoral resection. In 21 cases with a minimum follow-up period of 1 year (average, 33 months; range, 15 to 56 months), the 3-year disease-specific survival rate and the laryngeal preservation rate were each 95%. Normal food intake was eventually possible in all cases. Tracheostomy was performed for 2 patients as a prophylactic measure and for 1 patient because of a postoperative hemorrhage.Conclusions:These results indicate that videolaryngoscopic transoral en bloc resection using laparoscopic surgical instruments can be one of the minimally invasive treatment options for supraglottic and hypopharyngeal cancers with satisfactory oncological outcome and postoperative laryngeal function.

Objectives/Hypothesis:We have previously shown that gene therapy using Insulin‐like growth factor (IGF)‐I, glial cell line‐derived neurotrophic factor (GDNF), and brain‐derived neurotrophic factor (BDNF), or a combination of these trophic factors, is a treatment option for recurrent laryngeal nerve (RLN) palsy. However, there remain some difficulties preventing this option from becoming a common clinical therapy for RLN injury. Thus, we need to develop novel treatment option that overcomes the problems of gene therapy.

Objectives:The surgical options for laryngeal paralysis only achieve static changes of vocal fold position. Laryngeal reinnervation procedures have had little impact on the return of dynamic laryngeal function. The development of a new treatment for laryngeal paralysis, aimed at the return of dynamic function and neurologic restoration and regeneration, is necessary.Methods:To assess the possibility of gene therapy for laryngeal paralysis aiming for the return of dynamic laryngeal function, we investigated the therapeutic effects of gene therapy using rat laryngeal paralysis models.Results:In a rat vagal nerve avulsion model, we transferred glial cell line-derived neurotrophic factor (GDNF) gene into the nucleus ambiguus using an adenovirus vector. Two and 4 weeks after the GDNF gene transfer, a significantly larger number of surviving motoneurons was observed. These neuroprotective effects of GDNF gene transfer were enhanced by simultaneous brain-derived neurotrophic factor gene transfer. In a rat recurrent laryngeal nerve crush model, we transferred GDNF gene into recurrent laryngeal nerve fibers after crush injury. Two and 4 weeks after GDNF gene transfer, we observed significantly faster nerve conduction velocity and better vocal fold motion recovery.Conclusions:These results indicate that gene therapy could be a future treatment strategy for laryngeal paralysis. Further studies will be necessary to demonstrate the safety of the vector before clinical application.

AbstractCalcium phosphate cement (CPC) consists of powder and liquid, which become an injectable paste after mixing, self-hardening and recrystallizing to calcium hydroxylapatite (CaHA) after injection into a living body. In this study, we investigated the suitability of CPC as an injectable material for injection laryngoplasty using rabbits. All rabbits underwent left recurrent laryngeal nerve section and injection laryngoplasty with CPC. At 7 days, scanning electron microscopic findings revealed that complete recrystallization from CPC to CaHA was achieved in the larynx. At 1, 3, and 6 months, injected CPC stayed in the paraglottic space and did not migrate, and the average remaining CPC volume percentage was 91.7%. Focal foreign body reaction to injected CPC was almost the same as that of autologous fat for all time periods observed. These results indicated that CPC appears to be biocompatible, nonabsorbable, nonmigratory, and suitable for injection laryngoplasty.Copyright © 2006 S. Karger AG, Basel

Objectives/HypothesisThe authors have designed a rat laryngeal paralysis model to study gene transfer strategies using a muscle‐specific expression system to enhance local delivery of human insulin‐like growth factor‐1 (hIGF‐1). In preliminary studies, a nonviral vector containing the α‐actin promoter and human hIGF‐1 sequence produced both neurotrophic and myotrophic effects 1 month after single injection of plasmid formulation into paralyzed rat thyroarytenoid muscle in vivo. Based on these findings, it is hypothesized that the effects of hIGF‐1 will enhance the results of laryngeal muscle innervation procedures. The timing of gene delivery relative to nerve repair is likely to be important, to optimize the results.

Objectives/Hypothesis:To determine whether the myotrophic activity of human insulin‐like growth factor (hIGF)‐1 promotes restoration of normal myosin heavy chain (MHC) composition after nerve injury, MHC composition was analyzed after hIGF‐1 gene transfer in denervated rat laryngeal muscle.

OBJECTIVE: To derive a more precise description of vocal fold vibration, experimental phonation of excised canine larynxes was studied.STUDY DESIGN AND SETTING: Multiple X-ray-positive markers were inserted, and their vibratory movement was observed with x-ray stroboscopy with change of pitch and intensity. A histologic study was also carried out.RESULT: Regular waves were observed just above the lowest point of the lamina propria of the mucous membrane, which shifted upward at high pitch, but downward in high intensity.CONCLUSIONS: The starting point of the mucosal wave was confirmed on the lower surface of the vocal fold, histologically just above the lowest point of the lamina propria of the mucous membrane and shifted upward at high pitch, but downward in high intensity.SIGNIFICANCE: This is the first study investigating the starting point of mucosal wave in vocal fold vibration in a frontal plane using x-ray stroboscopy, providing the evidence for the body-cover theory.

ObjectivesTo test the hypothesis that myosin heavy chain (MHC) composition is a biological marker indicative of appropriate and functional reinnervation.

To derive a more precise description of vocal fold vibration, experimental phonation of excised canine larynxes was studied. Multiple X‐ray‐positive markers were inserted, and their vibratory movement was observed with x‐ray stroboscopy with change of pitch and intensity. A histologic study was also carried out. Regular waves were observed just above the lowest point of the lamina propria of the mucous membrane, which shifted upward at high pitch, but downward in high intensity. The starting point of the mucosal wave was confirmed on the lower surface of the vocal fold, histologically just above the lowest point of the lamina propria of the mucous membrane and shifted upward at high pitch, but downward in high intensity. This is the first study investigating the starting point of mucosal wave in vocal fold vibration in a frontal plane using x‐ray stroboscopy, providing the evidence for the body‐cover theory.

SUPERFAST myosin heavy chain (MHC), which is found in jaw-closing muscle and extraocular muscle (EOM), may also be found in rat laryngeal muscles. Immunostaining and Western blot using anti-EOM antibody were performed to identify and localize EOM MHC in laryngeal muscles. Specific reactivity of laryngeal IIL MHC was confirmed by Western blot and on immunostaining, all fibers in the lateral part of thyroarytenoid muscle reacted with EOM antibody. A scattered pattern of positive fibers was observed in the medial part of the thyroarytenoid, the posterior cricoarytenoid and the lateral cricoarytenoid muscles. EOM MHC was not detected in the cricothyroid muscle. The expression of EOM MHC in rat laryngeal muscle is consistent with the functional demands of the airway protection reflex.

The developmental transitions of myosin heavy chain (MHC) isoforms of rat posterior cricoarytenoid (PCA), thyroarytenoid (TA), cricothyroid (CT), and lateral cricoarytenoid (LCA) muscles were examined by means of sodium dodecyl sulfate—polyacrylamide gel electrophoresis (SDS-PAGE) and Western blot techniques. The muscles were microscopically dissected from animals on postnatal days 0, 3, 7, 10, 14, 21, 28, 35, 45, and 55 and from adult animals. Silver-stained SDS-PAGE gels of each muscle were analyzed densitometrically to measure the composition of MHC isoforms, and Western blot was carried out to identify specific bands. Characterizations of the internal laryngeal muscles determined by the composition of MHCs were correlated with their function in the adult. Temporally, differentiation reflects onset of function. Differentiation of isoforms and transition to adult forms occur first in the TA muscle, followed by the PCA, LCA, and CT muscles. Expression of type IIL was observed only in muscles innervated by the recurrent laryngeal nerve. Postnatally observed developmental differences of myosin phenotypes suggest that regulation of MHC expression is influenced by neural activity or other environmental factors.

Objectives:Myosin heavy chain (MHC) composition of human thyroarytenoid (TA), lateral cricoarytenoid (LCA), interarytenoid (IA), vocalis, posterior cricoarytenoid (PCA), and cricothyroid muscles were examined using sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS‐PAGE) and Western bolt techniques. The presence of superfast MHC was also assessed using antibodies directed against the extraocular MHC.

ABSTRACTCurrent surgical strategies for the treatment of laryngeal paralysis are limited by the muscle atrophy associated with denervation. Moreover, attempts at reinnervation have not effected significant change in surgical outcome. To address this clinical problem, we have developed a rat laryngeal paralysis model to study novel gene transfer strategies. Using this model, the human insulin-like growth factor I (hIGF-I) gene was introduced into paralyzed rat laryngeal muscle to assess the benefit of sustained local hIGF-I production. A muscle-specific nonviral vector containing the -actin promoter and hIGF-I gene was used in formulation with a polyvinyl-based delivery system and injected into paralyzed adult rat laryngeal muscle. Twenty-eight days after a single injection, gene transfer efficiency, muscle fiber size, motor endplate length, and nerve-to-motor endplate contact were evaluated. Gene transfer was detected in 100% of injected animals by PCR. Gene transfer with expression, as measured by RT-PCR for hIGF-I mRNA, occurred in 81.3% of injected animals. When compared with controls, hIGF-I-transfected animals presented a significant increase in muscle fiber diameter 17.56 (0.97 SD) m versus 14.70 (1.43 SD) m; p0.0002, a significant decrease in motor endplate length 20.88 (1.42 SD) m versus 25.41 (3.19 SD) m; p0.0025, and a significant increase in percentage of endplates with nerve contact (20.3% (13.9 SD) versus 4.4% (4.2 SD); p0.0079). In the context of laryngeal paralysis, gene therapy represents a tremendous opportunity to augment current surgical treatment modalities by preventing or reversing muscle atrophy, and by enhancing nerve sprouting and reinnervation.

AbstractTo evaluate how the viscosity of the laryngeal mucus influences vocal fold vibration, two fluids of differing viscosity were applied separately to excised canine larynges and experimental phonation was induced. Vibration of the vocal folds was measured by use of a laryngostroboscope and an X-ray stroboscope. With the high viscosity fluid, the amplitude of vibration of the free edge and the peak glottal area was decreased while the open quotient was increased. Because the viscosity of this fluid affected the wave motion of the vocal fold mucosa, changes in viscosity of the mucus may be involved in causing such disorders as hoarseness, in the absence of apparent changes in the vocal folds themselves.

Objectives: The effects of denervation on myosin heavy chain (MHC) expression in specific laryngeal muscles are characterized using gel electrophoresis. Observed temporal changes in MHC composition will then be used as a biologic marker in studies designed to develop strategies for laryngeal reinnervation and gene therapy. Study Design: Animal study using an adult rat model for laryngeal paralysis. Methods: In anesthetized rats the left recurrent and superior laryngeal nerve were divided. Animals were survived for 7, 14, 28, 90, and 180 days. Animals were euthanized and the thyroarytenoid (TA), vocalis (VOC), posterior cricoarytenoid (PCA), lateral cricoarytenoid (LCA), and cricothyroid (CT) muscle excised. Each muscle was processed for sodium dodecyl sulfate–polyacrylamide gel electrophoresis (SDS‐PAGE) and densitometric measurements were obtained to determine composition of MHC fiber types. Results: The changes in relative MHC composition are described for each specific laryngeal muscle. In general, a decrease in type IIB and an increase in HA and IIX are seen after denervation. Expression of IIL in the denervated condition is variable and the relative change in type I is minimal. Conclusion: This study supports previous work using rat soleus muscle in which IIA/IIX expression is favored in conditions with decreased neuromuscular activity, and conversely, IIB expression is activity dependent. Expression of type I appears to be independent of neural activity. Further study will be undertaken to quantify expression of MHC components and to study factors modulating expression.

We aimed to clarify the clinical features and surgical outcomes of descending necrotizing mediastinitis (DNM) to provide a guide for its surgical treatment, focusing on the type of extension and the deployed procedures.

Middle ear barotrauma is one of the common complications of SCUBA diving representing acute otalgia, hearing loss, and bleeding. But occurrence of facial palsy is rare. Here we report a case of a 30-year-old navy diver suffered middle ear barotrauma with transient facial palsy after SCUBA diving. He felt difficulty in equalizing the pressure in middle ear with Valsalva maneuver during diving, and suffered right facial palsy and aural fullness after diving. Clinical examination showed remarkable bulging of the right tympanic membrane and right facial palsy without other neurological findings. But facial palsy was disappeared immediately after myringotomy. We considered that the etiology of this case was neuropraxia of facial nerve in middle ear caused by over pressure of middle ear.

Nonspecific granuloma of the larynx is a benign tumor that usually occurs on the posterior glottis. Conventional treatment for this laryngeal lesion has consisted of surgical resection. However, this lesion has a strong tendency to recur postoperatively and may require multiple repeated operative procedures. Conservative treatment, consisting mainly of beclomethasone dipropionate inhalation therapy, was instituted in 20 cases with good results. We discussed the effect of beclomethasone dipropionate on this lesion as well as the etiology of this disease.

We produced specula for laryngomicroscopy to observe blind spots in the operating field. Use of these specula has facilitated detailed observation of the lower surface of the false vocal folds, laryngeal ventricle, and subglottis, which were previously in blind spots. The specula are useful in the following ways: 1) clarifying blind spots for improved diagnosis and providing more accurate surgical margins; 2) observing the lower lips of the vocal folds in phonosurgery; and 3) Vaporizing with laser reflection. The specula are cheap and easy to use and are well worth considering for application to laryngomicroscopy.

A rare case of lymphoepithelial cyst formed in the piriform sinus of the hypopharynx is reported. Histopathological examination revealed a lymphoepithelial cyst. It was removed by laryngomicrosurgical technique using a side-opened direct laryngoscope. Because this cyst was wide-based on the antero-medial region in the right piriform sinus of the hypopharynx, the mucous membrane around the cyst was incised electrosurgically and then detached to facilitate removal. In this paper, we describe our surgical procedure for removing the cyst in this case and discuss the possible causes of the disease.

We performed endoscopic phonosurgery in a patient with a laryngeal lesion using a prototype of the therapeutic rhino-larynx electronic endoscope connected to a video processor (Asahi Optical Co., Ltd.). This therapeutic electronic endoscope differs from the fiberoptic endoscope, because it contains an instrument channel and a miniature television camera attached to the tip of the endoscope, consisting of a small light-sensitive CCD chip. The dynamic image provided by this system is superior in resolution to that obtained by conventional flexible laryngofiberscopes. Using this therapeutic electronic endoscope and flexible forceps, we succeeded in removing a vocal fold polyp. This endoscope can be passed through the nasal passage into the laryngeal cavity. The therapeutic electronic endoscope is introduced and a clinical case is presented.