Acquired tracheal stenosis remains a challenging problem for otolaryngologists. The objective of this study was to determine whether the Sendai virus（SeV）-mediated c-myc suppressor, a far upstream element（FUSE）-binding protein（FBP）-interacting repressor（FIR）, modulates wound healing of the airway mucosa, and whether it prevents tracheal stenosis in an animal model of induced mucosal injury. First, a novel animal model for LTS was established. Next, we successfully demonstrated SeV-mediated transgene expression in the injured mucosa of the LTS model. Finally, a fusion gene-deleted, non-transmissible SeV vector encoding FIR（FIR-SeV/ΔF）was prepared. FIR-SeV/ΔF was administered to the rats with scraped airway mucosae through the tracheostoma. Untreated animals showed hyperplasia of the airway epithelium and a thickened submucosal layer with extensive fibrosis, angiogenesis, and collagen deposition causing lumen stenosis. In contrast, the administration of FIR-SeV/ΔF decreased the degree of tracheal stenosis and improved the survival rate. Immunohistochemical staining showed that c-Myc expression was downregulated in the tracheal basal cells of the FIRSeV/ΔF-treated animals, suggesting that c-myc was suppressed by FIR-SeV/ΔF in the regenerating airway epithelium of the injured tracheal mucosa. The airway-targeted gene therapy of the c-myc suppressor FIR, using a recombinant SeV vector, prevented tracheal stenosis in a rat model of airway mucosal injury.
Reconstruction of the upper airway after the resection of malignancies or stenotic inflammatory lesions is thought to be difficult. Postoperative scarring or granulation with stenosis is sometimes observed. Therefore, the regeneration of the respiratory tract with full functionality is vital after surgical treatment for cancer or inflammatory lesions.ES cell-like pluripotent cells, also known as induced pluripotent stem（iPS）cells, were generated from mouse skin fibroblasts by the introduction of 4 transcription factors in 2006. These cells are capable of unlimited symmetrical self-renewal, and thus provide an unlimited source of cells for tissue-engineering applications. In addition, the use of iPS cells obtained from patient-derived somatic cells can prevent transplant rejection.In this paper, using a technique for the differentiation of iPS cells, respiratory epithelium-like tissue was histologically observed, and the ciliary epithelium was immunohistologically confirmed. The transcript expression levels of CK14 were significantly increased in hiPS hVFF cultures. The cellular morphology was clearly cohesive and displayed a degree of nuclear polarity, which was suggestive of epithelial differentiation.Our results suggest that iPS cells could be a new source cells for use in the regeneration of the tracheal and laryngeal epithelium.
Laryngeal movements including breathing, phonation, and airway protective reflexes, such as swallowing and coughing, are mainly controlled by the neuronal networks in the brain stem. To understand the mechanisms underlying these movements, the morphological and functional properties of the brain stem neurons that participate in the production of these movements should be investigated. We previously examined the functional roles of the brain stem neurons that contribute to the generation of laryngeal movements using electrophysiological and morphological procedures. The findings of two studies are introduced in the presentation. In the first study, we reported the projections of the swallow-related neurons in the swallowing central pattern generator in the medulla oblongata using a tracer injection in anesthetized paralyzed guinea pigs. This study indicated that the swallowrelated neurons were broadly distributed in the nucleus tractus solitarius and reticular formation, and that there appeared to be complex interconnections amongst the nucleus tractus solitarius, the reticular formation, and the cranial motor nuclei. The other study showed that the activity of the respiratory neurons in the ventrolateral medulla, in particular between the Bötzinger complex and the rostral ventral respiratory group, was altered during fictive vocalization, swallowing, and coughing in a type-specific manner, and thus supported the hypothesis that the medullary respiratory neurons are multifunctional and that the respiratory center in the network circuitry underlying these behaviors can be shared.
Vitamin A（VA）storing vocal fold stellate cells （VFSCs）, which are found in the anterior and posterior maculae flava（MFs）, are expected to play crucial roles for maintaining the lamina propria（LP）and scar formation in the LP. However, the knowledge on the in vivo and in vitro features of VFSCs is limited. In the present study we compared the features of VFSCs among various species to identify the most appropriate model for a subsequent in vivo study, and cultured primary VFSCs from humans to elucidate the in vitro features. Larynges from humans, dogs, pigs, rabbits and rats were excised and subjected to immunostaining for glial fibrillary acidic protein（GFAP）in VFSCs, and staining for VA and lipid droplets（LD）and VA measurement. VA storing VFSCs located at the MFs were only identified in humans and rats in which the amounts of VA stored in the VF were similar. Primary VFSCs（pVFSCs）and vocal fold fibroblasts（pVFFs）were isolated from human larynges and cultured for immunostaining for VFSC markers（GFAP and vimentin）, and for VA measurement. The expression levels of the VFSC markers and VA storage were identified in the pVFSCs and pVFFs in the same manner as in the in vivo VFSC experiments. The present study revealed that rats and cultured pVFSCs were useful for in vivo and in vitro VFSC studies, respectively.
We have performed endoscopic laryngomicrosurgery under general anesthesia for 14 years; during this time, all of these procedures have been successful. Endoscopic laryngomicrosurgery for midmembranous vocal fold lesions, including polyps, nodules and cysts were easily and safely performed under a video-laryngoscope, especially when a high vision monitoring system was used. In this paper, we present a number of tips for performing endoscopic laryngomicrosurgery for midmembranous vocal fold lesions under general anesthesia.To prevent the tremor of the surgeon’s fingers during the microflap maneuver, a multitask arm board was found to be useful as an arm-rest. Furthermore, the placement of a cotton ball at the subglottis was useful for stabilizing the apex of a forceps during the resection of midmembranous vocal fold lesions.
Microlaryngoscopic surgery, which enables the observation of the microscopically magnified vocal fold while operating by maintaining the vocal fold in a resting state under general anesthesia, is the most common method of phonosurgery. It has a wide range of applications from phonosurgery for vocal fold membranous lesions including vocal fold polyps, vocal fold nodules, and Reinke’s edema of the vocal fold to phonosurgery for diseases such as unilateral vocal fold paralysis and spasmodic dysphonia. It is therefore considered one of the most useful treatment methods currently available.We herein introduce the standard method of microlaryngoscopic surgery carried out at Osaka Voice Center, in terms of basic surgical methods along with surgical procedures for specific indications.
There are many opportunities for otolaryngologists to experience the treatment of vocal fold polyps, nodules, cysts and polypoid lesions. The purpose of laryngomicrosurgery is to normalize the obstructed mucous membrane wave motion and glottis closure. When performing an operation, we note in particular the removal of a pathological change, preservation of the mucous membrane and balance from right to left, front to back. Saito’s forceps are used with a little gap for the extraction of a polyp. When using Saito's forceps effectively, it is possible to perform an operation with few tools.
Transoral Laser Microsurgery（TLM）with a CO2 laser is an alternative treatment to radiotherapy（chemoradiotherapy）for early glottic cancer. Generally, the indication for TLM is based on the patient’s age, general condition, or the preference of the patient or physician as well as the tumor site and its extent, or penetration. At Kurume University Hospital, TLM alone was performed as the primary treatment for 77 patients with early glottic cancer from 1986 to 2011. The T classifications of the patients were as follows: Tis（n=11）,T1a（n=56）, T1b（n=5）, and T2（n=5）. The types of cordectomy were classified, according to the European Laryngological Society Classification, as follows; type I （n=24）, type II （n=8）, type III （n=32）, type IV （n=3）, type Va （n=5）, type Vb（n=3）and type VI（n=2）. In the present study, after explaining our surgical procedures, we describe the treatment outcomes and postoperative voice quality of the patients. The main findings of this study were as follows: 1） the 5-year local control rate was 93.0% in TLM alone; 2） the aerodynamic functions stabilized about 6 months after TLM alone; and 3） the patients’ phonatory functions were significantly poor after Type III cordectomy that included the anterior macula flava.
Transoral surgery for laryngeal cancer is becoming a major treatment option due to the increasing need for laryngeal preservation. In our department, transoral laser microsurgery（TLM）is mainly performed for glottis cancer, and transoral videolaryngoscopic surgery（TOVS）, which we established, is performed for supraglottic cancer.The indications for TLM for glottis cancer are Tis, T1, T2, and select T3 cases with vocal fold movement, without invasion into the thyroid cartilage and/or cricoid cartilage. Salvage surgery is indicated for select resectable cases less than rT2 cases. Two-staged surgery is recommended for T1b cases. The indications for TOVS for supraglottic cancer are resectable T1, T2, and select T3 cases with vocal fold movement, without invasion into the thyroid cartilage, cricoid cartilage and/or hyoid bone. Salvage surgery is indicated for select resectable cases less than rT2 cases.The oncological outcome is similar to that of（C）RT or open partial laryngectomy. Vocal function after TLM is also similar to that after（chemo）radiotherapy. The swallowing function after TOVS is favorable.It is important to understand the differences in the indication for open partial laryngectomy and to have the proper knowledge to recommend appropriate treatment options for patients.
The purpose of this study was to elucidate the appropriate time for closing a tracheoesophageal shunt for a safe and non-invasive surgical procedure, after acquiring another type of vocal rehabilitation. A tracheoesophageal shunt is globally considered to be the most useful tool for excellent vocal rehabilitation; nevertheless, it must be closed for several reasons. In some cases, surgical closure of a tracheoesophageal shunt is difficult due to poor histological conditions around the shunt. We herein propose a new strategy of vocal rehabilitation to utilize a tracheoesophageal shunt effectively.Materials and methods: Between 1995 and 2014, 46 patients underwent voice prosthesis insertion surgery. Nine （eight laryngeal cancer patients, one thyroid cancer patient） of these patients underwent surgical closure of a tracheoesophageal shunt. We investigated their cancer treatments, reasons for closing the tracheoesophageal shunt, period of voice prosthesis insertion, operative method, number of operations, and outcome.Results: The reasons for closing the tracheoesophageal shunt were aspiration pneumonia and acquisition of esophageal voice in 4 patients each. Regarding the period of voice prosthesis speech, 6 patients had used it for approximately 3 years and 3 patients for more than 7 years. Approximately all 3-year users underwent a non-invasive surgical procedure, such as triple-layered suture, and their operation succeeded the first time. Conversely, the more than 7-year users required an invasive surgical procedure, such as a pedicle flap, and had to undergo more than one operation.Conclusion: In the present study, tracheoesophageal shunt closure could be performed within 3 years via a safe and non-invasive surgical procedure. We recommend that the operation for a tracheoesophageal shunt be undertaken at a relatively early stage after total laryngectomy. Such patients should acquire esophageal voice within 3 years and undergo surgical closure of the tracheoesophageal shunt as soon as possible.
Multiple paralysis of the cranial nerves secondary to tuberculosis is rare. We herein report the case of a patient with tuberculous cervical lymphadenitis who presented with unilateral paralysis of the 9th, 10th and 11th cranial nerves and hypertrophy of dura mater with diagnostic challenges. The patient was a 62 year-old female who visited us with dysphagia and hoarseness of a few weeks in duration. A physical examination and laryngopharyngeal fiberscopy revealed the paralysis of the patient’s right vocal cord, soft palate and the trapezius muscle, while all of the laboratory and imaging examinations initially showed unremarkable results. PET and repeated head MRI scans were conducted two months later because of the patient’s severe weight loss, fatigue and headache. The PET scan showed the abnormal uptake of FDG in the right jugular foramen and both of the upper cervical nodes. MRI showed dural hypertrophy in the left cerebellar tentorium. Cervical lymph node biopsy was performed to search for possible malignancies. Based on the biopsy results, the patient was diagnosed with tuberculosis with the absence of lung lesions. The patient’s multiple nerve palsy, headache, and dural hypertrophy improved after six months of antituberculosis therapy. Thus, the patient’s jugular foramen syndrome and hypertrophic pachymeningitis were diagnosed as secondary symptoms of tuberculosis. Tuberculosis is one of the differential diagnoses that should be considered in patients with multiple cranial neuropathies with few clinical findings.
A 25 -year-old man who had a history of acute mumps infection at 3 years of age presented with a sore throat and high fever. A local otolaryngologist noticed the severe swelling of his salivary glands and laryngeal edema and the patient was referred to our hospital. A physical examination showed the severe bilateral swelling of the parotid and submandibular glands. Laryngeal fiberscopy indicated an advanced edematous change in the supraglottis. Enhanced computed tomography of the neck revealed swelling of the salivary glands and cervical lymph nodes with no evidence of abscess. Laboratory tests showed a leukocyte count of 6.6×103/μL（neutrophils 75.8% , lymphocytes 17.8% , and monocytes 5.8%）, a CRP level of 1.56 mg/dL, and a serum Amylase level 992 IU/L. After admission, tracheostomy was performed. The diagnosis of mumps was confirmed by the elevation of mumps-specific immunoglobulin M titers. Laryngeal edema associated with mumps is thought to be caused by lymphatic congestion, secondary to salivary gland enlargement due to inflammation. It is therefore essential to examine the airway by laryngoscopy in mumps patients with swelling of the submandibular and parotid glands.
We herein report the case of a patient with delayed laryngeal stenosis caused by an inhalation injury. The patient was a 24-year-old male who suffered a burn to 17% of the body surface area of his body and a severe inhalation injury. He was intubated for 10 days until his laryngeal edema improved. Three months after the injury, he started to complain of respiratory distress which was found to be caused by posterior glottic adhesion. After surgery, his vocal cord movement showed sufficient improvement and the respiratory symptom disappeared. However, he started to complain of respiratory distress again. The cause of the complaint was found to be circumferential subglottic stenosis. A T-tube was placed to prevent subglottic stenosis for 30 months before the tracheostomy was closed. Subglottic restenosis has not been observed thus far, however, a continuous and careful follow-up is required.
Laryngeal cleft（LC）is rare congenital abnormal malformation. It is considered to be developmental anomalies due to failure of the fusion of the tracheoesophageal septum from fourth to eight embryonic weeks. LC have a number of airway symptom including aspiration and recurrent pneumonia.We herein experienced that a cause of arytenoid mucosal edema due to LC. This case was a 3-year-old girl. Her chief complaint was stridor and dyspnea. We observed her arytenoid mucosal edema and motion, such as the pendulum motion using a laryngeal endoscope. We considered that the potential causes of the arytenoid mucosal edema were allergy, laryngopharyngeal reflect disease（LPRD）and laryngomalacia. However, the arytenoid mucosal edema persisted after surgery. During the 4th operation, we noticed a LC. The patient currently does not have increased mucosal swelling, and is not suffering from aspiration and stridor.Type I LCs are largely undiagnosed in children. The diagnosis and management of LC is often delayed because it is difficult to diagnose LC. The diagnosis of LC must be made with the laryngoscope.