Recurrent respiratory papillomatosis (RRP) is a type of papillomatosis that frequently recurs in the airway after surgery. To suppress the aggressiveness of this disease, several adjuvant therapy options have been presented. However, no concrete approach for managing RRP has been developed. We conducted a series of studies to examine the effect of human papillomavirus (HPV) vaccination as adjuvant therapy for RRP and review the findings here. We first demonstrated the specific frequency of the HPV-6 or HPV-11 infection rate of laryngeal papilloma among various laryngeal diseases, including polyps, nodules, cysts, leukoplakias, and carcinomas. Another study showed significant increases in the HPV antibody titer in 12 RRP patients after HPV vaccination. We further showed that the HPV infection status changed from “positive” to “negative” by 12 months after surgery following HPV vaccination among nearly 70% of 12 RRP patients. Our latest study showed a significant reduction in both the disease severity and tumor existence rate after surgery following HPV vaccination for approximately 80% of 16 RRP patients. Our previous findings suggest that HPV vaccination may be a viable adjuvant therapy option for RRP.

Laryngeal papilloma (LP) is a tumor caused by infection of the larynx with human papillomavirus type 6 or 11 (HPV-6 or HPV-11) and is a multiple, recurrent, and refractory disease. HPV-6 and HPV-11 have nine genes, but the detailed functions of these genes in the formation of recurrent and refractory LP have not been elucidated. We examined the viral DNA load and mRNA expression as well as the in situ localization in HPV-6-infected LP. Our novel phage display method produced a monoclonal antibody against the viral E4 protein as E4 mRNA was found to be the most highly expressed of the nine viral mRNAs. The average viral load was 4.80 × 10⁵ ± 1.86 × 10⁵ copies/ng DNA. E4, E5a, and E5b mRNAs accounted for 96% of the expression of the 9 mRNAs. The changes in the viral DNA load and expression of the nine mRNAs showed a similar curve during recurrence. The E4, E5a, and E5b mRNAs were co-expressed in the middle to the upper part of the epithelium. These results suggest that individual viral genes are coordinately expressed for viral replication, virus release, and immunosurveillance avoidance. Antibody against HPV-6 E4 shows high sensitivity and specificity in western blotting and immunohistochemistry and can be used for further functional studies and clinical applications.

Laryngeal papilloma is a benign intraepithelial tumor caused by human papilloma virus (HPV) type 6 or 11. Because of latent HPV infection in the epithelial basal cells, the papilloma frequently recurs. Since the optimal medication strategy has not yet been established, the main treatment is surgical removal. To perform precise papilloma surgery, the histological characteristics of the laryngeal mucosa, as well as laryngeal papilloma, are important to consider. A frequent site of papilloma is the epithelial junction between stratified squamous epithelium and pseudostratified ciliary columnar epithelium, although HPV can infect each type of epithelium. Not only the susceptibility and infection of HPV but also epithelial stratification play an important role in the development of papilloma. The aim of the surgery is complete removal of the papilloma with little scar formation and adhesion of the mucosa, which can cause voice disorder and airway stenosis. To achieve this aim, subepithelial resection along the basal lamina is crucial. Removal of the superficial lamina propria, as in ELS type I cordectomy, should be avoided. To reduce scar formation and adhesion after wide-range tumor resection, performing wound sealing with a polyglycolic acid sheet is useful. This method prevents tissue deficit and delivers a larger mucosal amplitude of the vocal fold mucosa.

Objectives : The treatment of recurrent respiratory papillomatosis (RRP) continues to be difficult. We evaluated the benefits and risks of the intralesional administration of cidofovir for severe RRP in 13 patients.

Methods : Thirteen patients received intralesional cidofovir. The surgeries were performed three times every two weeks, with intralesional injections of cidofovir (7.5 mg/ml). A further endoscopic evaluation was made at three months depending on whether there was persistent papillomatosis. The intrelesional injection of cidofovir with CO₂ laser vaporization was performed in the case of persistent papilloma, and treatment was repeated as long as papillomas were observed.

Results : One of 13 patients achieved complete remission and seven achieved partial remission. Five patients showed a poor response to cidofovir. No side effects related to cidofovir were observed in 13 patients.

Conclusion : The results of the study indicate that the intralesional injection of cidofovir can be an effective treatment method for recurrent respiratory papillomatosis.

Although laryngo-tracheal papilloma, also known as recurrent respiratory papillomatosis, is a benign disease, it tends to recur and spread throughout the larynx and trachea. The incidence rate in Western countries has been reported to be less than 1 per 100,000 for both juvenile-onset and adult-onset types. Surgical approaches to managing this disease have varied over time. For example, a carbon dioxide laser was the most popular modality in the 1990s in the United States, whereas a microdebrider has been widely used since the 2000s in both the United States and Europe. Our previous survey revealed that a carbon dioxide laser, microdebrider, and cold steel surgery were used with almost equal frequency in Japan. We are currently conducting a nationwide survey that will help clarify the epidemiology of this morbid disease in Japan. The disease is caused by human papillomavirus (HPV), especially the low-risk types of HPV6 and HPV11. Therefore, the 4- and 9-valent HPV vaccine may reduce the incidence of this disease, as observed in anogenital warts.

Subglottic stenosis has congenital as well as acquired causes. Acquired subglottic stenosis overwhelmingly occurs in patients with a history of endotracheal intubation. Children with a narrow airway may be prone to restenosis with early surgery. However, children also have social issues that need to be considered, such as the timing of language development and the need for schooling, so it is best to balance these factors and perform treatment at an appropriate time. If the subglottic stenosis is mild to moderate, minimally invasive endoscopic surgery, such as laser therapy or balloon dilation, is an option, while open airway reconstruction is considered for severe stenosis. In this article, we describe the treatment strategies in place at our hospital.

Airway stenosis is a rare, life-threating disease requiring the early establishment of management guidelines. However, because of its rarity, evidence concerning this pathology is sparse. To understand the actual situation in cases of pharyngeal, laryngeal and tracheal stenosis, a nationwide questionnaire survey is being conducted. Furthermore, a patient registry for cases of pharyngeal, laryngeal and tracheal stenosis is also being constructed for the prospective accumulation of guaranteed patient information. New evidences concerning airway stenosis is expected to be generated through these studies.

As a novel reconstructive implant, an in situ tissue regeneration-inducing artificial trachea made of polypropylene and collagen was developed in Japan. Clinical trials to validate the safety and efficacy of this artificial trachea have already been completed, and the early clinical application of this material is expected.

Posterior glottis stenosis (PGS), which is caused by endotracheal intubation, laryngeal trauma and others, is often misdiagnosed as bilateral vocal fold paralysis (BVFP). Bogdasarian has categorized PGS into four types according to the pathological condition of the larynx. Type Ⅳ, involving ankylosis of the cricoarytenoid joint, is the most common but particularly difficult to manage. PGS can be diagnosed based on a patient’s medical history and findings of fiberoptic laryngoscopy, computed tomography (CT) and direct laryngoscopy without laryngeal electromyography. In patients with tracheostomy, a transtracheal examination of the glottis and subglottis with the tracheotomy tube removed helps discriminate between PGS and BVFP. Ankylosis of the cricroarytenoid joint can be confirmed by the passive movement test during direct a laryngoscopic examination. The posterior glottis in PGS type Ⅳ cannot be widened by Ejnell’s laterofixation procedure. If a patient desires tracheal stoma closure, laterofixation combined with aryntenoidectomy should be performed after the patient has been informed of the possibility of deterioration of the voice quality. Staged surgeries may be considered if necessary. If a patient desires the preservation of their voice quality, tracheal stoma is essential, and arytenoidectomy, which degrades the voice quality less severely than laterofixation, may be required to use a speaking valve constantly.

Radiotherapy plays an essential role in the function-preserving treatment of elderly patients with laryngeal cancer. Regarding early glottic cancer (GC), accelerated fractionated radiotherapy (Ax) is believed to be a useful treatment option for GC because of its convenience in reducing the treatment time, cost, and labor. In JCOG 0701, Ax showed comparable efficacy and safety to standard fractionated radiotherapy. In addition, real-world data and evidence from clinical research have also shown promising findings concerning Ax for GC. Regarding radiation techniques for advanced laryngeal cancer, intensity-modulated radiation therapy (IMRT) is very useful for reducing late toxicity, especially for concurrent chemoradiotherapy (CCRT). Less-invasive treatment using IMRT is now being evaluated in many on-going trials, and the JCOG1912 trial has just started to assess the non-inferiority in less-invasive treatment in CCRT using IMRT for locally advanced head and neck cancer. We herein report the results of our organized prospective observation study for patients using radiotherapy with cetuximab in the JROSG12-2 trial. I sincerely appreciate the opportunity to introduce our findings at the 33^rd annual meeting of the Japan Laryngological Association.

This study examined the feasibility of carbon dioxide (CO₂) transoral laser microsurgery (TLM) for early glottic carcinoma in Japanese patients over 75 years old. A retrospective chart review was performed for 43 patients with (r)Tis-T2 glottic cancer who underwent TLM in our institution between 2010 and 2018. The oncological results, postoperative voice/swallowing function, and complications were evaluated. Results show that TLM is a viable option for Tis and T1a cases when general anesthesia is possible. TLM appears to be appropriate for T1b lesions that are clear and localized. However, if type Ⅵ cordectomy is required, prolonged hospitalization owing to aspiration may occur. T2 carcinomas with unclear lesion extension may require salvage treatment. In salvage cases, TLM should be carefully considered according to the extent of lesion progression at the time of the initial treatment and postoperative complications. The postoperative voice function was found to be equivalent to that observed after radiation therapy, and approximately 80% of patients were able to start oral intake the day after surgery. TLM is minimally invasive and requires a short hospital stay, making it an attractive treatment option for elderly patients. Furthermore, actively performing transoral surgery in elderly patients should be encouraged.

We investigated the 12-year trends in the treatment of elderly patients with laryngeal squamous cell cancer ≥ 75 years old in our department. We also describe the future prospects. In Japan, the number of elderly people ≥ 75 years old has increased since the beginning of the Heisei era, and accordingly, patients with laryngeal squamous cell cancer have been aging as well. In the 12-year transition period in our department, the proportion of elderly patients among all laryngeal squamous cell cancer cases increased from 25% in 2007-2010 to 40% in 2015-2018. We noted no marked difference in the overall survival between non-elderly and elderly patients. Regarding laryngeal preservation treatment, there were only a few cases in which anticancer drugs were used in the treatment plan of elderly patients. In recent years, geriatric oncology has been attracting attention, and there is a movement to generate evidence supporting the optimal treatment of elderly patients in the future. In Japan, the healthy life expectancy is increasing more rapidly than in the rest of the world, suggesting the need to actively pursue research into effective cancer treatments for the elderly.

In recent years, Japan’s population has been aging. As a result, there are more and more opportunities to treat voice disorders in the elderly. However, elderly individuals often have more complications and a poorer performance status than the general population, which limits treatment options. Therefore, we believe that minimally invasive treatment is extremely important. With this in mind, we have been actively performing intra-vocal atelocollagen implantation as a minimally invasive and simple surgical treatment for vocal fold atrophy, vocal fold sulcus, and vocal fold paralysis in the elderly. A total of 193 patients underwent intra-vocal collagen implantation between April 2015 and September 2020, of which 123 were elderly patients over 65 years old. The changes in the phonological evaluation before and after the treatment were statistically evaluated and reported. We also present two cases of elderly patients who benefited from intracordal atelocollagen injection.

Japan is currently facing a super-aged society, with an aging rate of 28.7% as of 2020 amid a declining birthrate and a growing proportion of elderly people. The elderly population visiting voice clinics has shown an increasing trend, with an aging rate of 43% among new patients at the author’s vocal outpatient clinic in the past 5 years. Thus, an understanding of the clinical features and frequent/infrequent laryngeal disorders as well as and how to evaluate the elderly population is more than ever important. A statistical analysis of new patients at our voice clinic revealed that laryngeal leukoplakia, laryngeal cancer, vocal fold atrophy (presbyphonia), vocal fold paralysis, and sulcus vocalis were frequent in the elderly population. Given the associated clinical consequence, the detection of laryngeal cancer is considered particularly important in cases dysphonia among the elderly. Furthermore, presbyphonia requires extra attention, as its rate is increasing due to societal aging, while its clinical entity remains ambiguous. Several issues remain to be addressed in the future for cases of presbyphonia, including the disease name, delineation between normality and abnormality, and age limit.

The aging rate in Japan was 28.4% in 2019. In this super-aged country, effective treatment for vocal fold atrophy in elderly patients (>65 years old) is urgently required. In our clinic, voice therapy is the first-choice therapeutic procedure for vocal fold atrophy, with surgery considered should voice therapy prove ineffective for managing vocal fold atrophy. This therapeutic strategy of selecting a less-invasive procedure as a first-choice therapeutic option is universal and realistic for elderly patients. It has been reported that voice therapy can improve vocal fold vibrations by improving the contractile function of the atrophic thyroarytenoid muscle. Various studies have reported the efficacy of voice therapy for managing vocal fold atrophy. In recent years, various approaches have been used in the hopes of achieving greater therapeutic efficacy than with traditional methods in the field of speech therapy.

Oxidative stress causes many pathologies, such as cancer, disease, and aging. The vocal fold is also affected by oxidative stress due to long-term voice use and/or in the course of aging. The vocal fold becomes thin and stiff with age, causing a breathy, weak voice. We confirmed that reactive oxygen species (ROS) are significantly increased with age in the lamina propria of the vocal fold mucosa, whereas hyaluronic acid (HA) levels in the vocal fold are decreased. ROS also increases after injury to the vocal fold, leading to long-term scarring of the vocal fold. The application of an antioxidant has proven useful for reducing ROS in the vocal folds after injury or during aging, helping maintain a healthy vocal fold. We also confirmed that antioxidant agents are useful for maintaining the phonatory function after a vocal load task and for maintaining a professional singer’s voice. It is important to control oxidative stress in order to maintain the function of the vocal fold throughout aging.

Laryngeal partial laryngectomy can be broadly divided into trans-oral cordectomy, vertical partial laryngectomy, horizontal partial laryngectomy, and supracricoid partial laryngectomy. It was developed as a laryngeal-preserving surgery in the early 20th century and has since become one of the most important laryngeal-preserving treatments for laryngeal cancer. Trans-oral cordectomy is a standard treatment for early-stage cancers, and the indication should be considered by taking into account the different factors associated with the tumor, patient, and medical staff. Open partial laryngectomy is mainly positioned as a salvage treatment for post-RT recurrence. It can also be used for the initial treatment of patients with anterior segment or selected advanced cancer; good results have been obtained with this treatment. A downward trend in the number of partial laryngectomies is expected, but as the late effects of radiotherapy become an issue, the role of laryngeal preservation surgery should receive focus once more. In our super-aging society, we will encounter dysphagia due to aging with increasing frequency. Achieving total laryngectomy and postoperative rehabilitation are more important than preserving the larynx for elderly patients.

Thyroplasty type I (TPI) and arytenoid adduction (AA) in laryngeal framework surgery, as developed by Isshiki, have been the surgeries of choice for unilateral vocal fold paralysis (UVFP). This paper mainly describes the surgical indications and techniques of these surgeries performed in our department. When performing TPI, it is important to correctly open the window in the thyroid cartilage and preserve its inner perichondrium. It is also necessary to devise a way to deal with osteochondral lesions found in the thyroid cartilage. However, a more reliable and less invasive way of approaching the muscle process of the arytenoid cartilage when performing AA is sought. Using preoperative three-dimensional reconstructed computed tomography (3DCT) images, we can determine the fenestration position during TPI. Furthermore, by evaluating the locations of inserted material after TPI or arytenoid cartilage after AA using postoperative 3DCT images, we can obtain feedback on who to further improve our surgical technique.

Mutational disorder (MD) and gender identity disorder (GID) are rare disease. Such patients tend to complain that their speaking fundamental frequency (SFF) does not fit, being too high or too low. Type 3 thyroplasty (TP3) reduces the pitch of the SFF. In detail, the tension of the vocal fold is loosened by TP3, which then causes the the SFF to become low-pitched. Type 4 thyroplasty (TP4) conversely increased the pitch of the SFF as the tension of the vocal fold is tightened causing the SFF to become high-pitched. While vocal pitch disorders are not life-threatening for patients with MD and GID, they can cause substantial worry and stress. TP3 and TP4 can thus improve the quality of life of the patients with MD and GID.

In this paper, we described roles of speech therapists (STs) in the treatment of voice disorders and collaboration between otolaryngologists and STs in our hospital. The main role of STs in the treatment of voice disorders is voice therapy. Voice therapy is indicated when patients have issues producing a voice with or without organic diseases. When starting voice therapy, it is of vital importance to select the optimal method from among various techniques and demonstrate its efficacy on the spot as much as possible. We herein report the results of collaboration between otolaryngologists and STs at our hospital. Otolaryngologists and STs interview patients and evaluate their voices together. An ST is also present at the time of thyroplasty under local anesthesia, and they evaluate the patient’s voice in order to ensure optimal adjustments are made. In addition, we hold weekly conferences and study sessions. We believe that mutual understanding and close collaboration between otolaryngologists and STs is mandatory when treating voice disorders.

Treatments for voice disorders consist of surgical intervention, medical intervention, and voice therapy. Voice therapy has primarily been applied in cases of nonorganic dysphonia, including muscle tension dysphonia and mutational falsetto. However, the application of voice therapy has recently expanded to include benign vocal fold lesions, presbyphonia, and vocal fold paralysis, among other targets. Otolaryngologists need to determine the appropriateness of the application of voice therapy and thus must be familiar with the evidence supporting voice therapy. In addition, to facilitate voice therapy, it is important for a speech language pathologist (SLP) to attend medical examinations performed by an otolaryngologist. This enables otolaryngologists and SLPs to share knowledge concerning the patient’s laryngeal function as well as the patient’s wishes. These will create synergy that will promote effective patient care.

We herein review the typical surgical treatments and current status of the regenerative approach for sulcus vocalis. Sulcus vocalis demonstrates as pathophysiology of the fibrosis in the VF (Vocal Fold) as VF scarring and is one of the main reasons for permanent dysphonia, resulting from injury to the unique layered structure of the VFs. The clinical pathology of sulcus vocalis has been classified as types Ⅰ to Ⅲ based on previous research from Ford. However, the diagnosis may be difficult, even with the help of stroboscopy, and the etiology remains controversial, with arguments for each theory still underway. Surgery with supplementary injection laryngoplasty of the VFs is the main treatment option for pathological sulcus vocalis. However, other effective treatment options based on regenerative medicine are needed. According to previous basic research, the increased collagen and decreased hyaluronic acid within VF scarring lead to a loss of pliability of the VFs and thereby significantly decrease their capacity to vibrate. As there is currently no definitive treatment for VF scarring, regenerative medicine and tissue engineering have become increasingly important research areas within the field of otolaryngology. This review focuses on emerging techniques for restoring VF pliability using various approaches, including surgical procedures. We also identify several obstacles hindering further advances in this area of research.

Vocal fold scarring and sulcus vocalis remain major therapeutic challenges in voice therapy. The loss of the superior lamina propria results in a change to the pliability of the vocal folds, along with changes in the glottal configuration and glottal closure and a reduced to absent mucosal wave motion. This results in dysphonia of varying severity, including breathiness, roughness, loss of pitch range, and flexibility. The dysphonia caused by vocal fold scarring and sulcus vocalis is often severe and difficult to treat, and no suitable voice therapy has been established, let alone validated in a prospective study. We performed voice therapy for patients with mild to moderate vocal fold scarring and sulcus vocalis and functional problems, such as an alternative hyperfunctional voice or vocal misuse. The concept of voice therapy in our clinic involved the following: minimizing vocal effort, optimizing the vocal quality, and developing vocal flexibility. As a result, the vocal function has significantly improved with regard to various vocal parameters in aerodynamic assessments, acoustic analyses, stroboscopic examinations, and self-evaluations. Ten of 13 patients completed treatment for vocalization through voice therapy, without the need for additional treatments. Three of the 13 patients showed an improvement in their vocal function on inspection, although they were not satisfied with their professional voices. These results indicate that voice therapy has potential utility for improving the vocal function in patients with mild to moderate vocal fold scarring and sulcus vocalis.

There is growing evidence that the cells in the maculae flavae are tissue stem cells and that the maculae flavae are a stem cell niche of the human vocal fold mucosa. The stem cell system of the tissue stem cells of the human adult and newborn vocal fold mucosa, including the heterogeneity and hierarchy of the cells, was reviewed and summarized.

Regarding the heterogeneity, cobblestone-like polygonal cells, vocal fold stellate cell-like cells possessing lipid droplets in the cytoplasm and fibroblast-like spindle cells were intermingled in the maculae flavae under light and electron microscopy, indicating that three phenotypes of cells were present in the human adult and newborn maculae flavae in vivo.

Regarding the hierarchy, cobblestone-like polygonal cells are at the top, while fibroblast-like spindle cells are at the bottom of the cellular hierarchy in the stem cell system. Therefore, vocal fold stellate cell-like cells in the human maculae flavae are likely at the second level of the cellular hierarchy. This suggests that the vocal fold stellate cell-like cells are progenitor cells or transiently amplifying cells in the stem cell system of the human vocal fold mucosa.

The cells in the maculae flavae of the human adult and newborn vocal fold mucosa have heterogeneity and hierarchy in the stem cell system in vivo.

Voice therapy (VTx) is applied to patients with dysphonia for improvement of functional aspects. It usually takes several months to complete the therapy, and relatively high rates of drop-out remains issue. Intensive voice therapy is a novel treatment approach which concentrates the period of therapy as short as possible. Intensive VTx has been proven to be equally effective in treating patients with dysphonia as long-term VTx. It is also shown that the rate of drop out of intensive VTx is lower than long-term VTx. We have applied intensive VTx for patients who could not receive long-term VTx, and report here the effects. As a result, sufficient improvement in vocal function was obtained in a short period of time in our cases without drop out, arranging the content and application of treatment.

Future prospective studies will be needed to examine the optimal treatment protocol and schedule as intensive VTx which is suitable in Japan.

Background and Objectives: Ultra-high-resolution Computed Tomography (UHRCT) was recently released as a next-generation imaging technology. This novel technology can deliver 160 simultaneous slices with a super-thin 0.25-mm thickness, and we previously reported the feasibility of UHRCT for visualizing the vocalizing larynx. The present study examined the clinical feasibility of UHRCT for visualizing cuffed endotracheal tubes and surrounding tracheal structures in tracheostomized patients.

Materials and Methods: Two patients who would require future laryngotracheal separation procedures were included in this study. One patient (33 years old, male) had cerebral hemorrhaging, and the other (57 years old, female) had multiple system atrophy inducing chronic respiratory distress and dysphagia. UHRCT was performed with the patients in the supine position, and 3D reconstruction of the cervical tracheal regions was performed. The shapes of the endotracheal tubes, cuff, and surrounding tracheal structures were examined using the reconstructed images.

Results: Reconstructed UHRCT images clearly visualized the flange, shaft, cuff, cuff inflation line, and suction line of endotracheal tubes. While the cuff pressures were properly controlled (20-25 mmH₂O), the inflated tracheostomy tube cuff was observed in the folds of the cuff wall, and the distal tip of the cannula did not stay in the middle of the trachea in one patient.

Conclusions: This was the first study to show the clinical utility of UHRCT for assessing cuffed endotracheal tubes and the surrounding tracheal structures. Our findings support the idea that the inflated cuff and folds in the cuff wall in vivo visualized by UHRCT could predict an air leakage and aspiration of fluid.

When the larynx is removed due to laryngeal or pharyngeal cancer, the vocal cords are permanently lost. An electric larynx (EL) is used as a communication device for patients after total laryngectomy. Laryngectomized patients have been using an EL as a means of communication for some time. However, the EL has a drawback in that it requires one hand to be used when speaking and can only produce a limited range of mechanical sounds (60 to 200 Hz). Furthermore, the appearance and main specifications of the device have hardly changed since it was first introduced. To solve these problems, we developed a new electric EL (hands-free EL) that reproduces realistic speech in a hands-free manner. This is the first report on the status of the development of this EL. In the development of our hands-free EL, we aimed to generate sounds close to those of natural voices for both men and women and to create a stylish hands-free design. With the hands-free EL, two different types of vibrators were used to produce a wide frequency range stably. In addition, the frequency of the vibrations was kept closer to that of a natural voice than with a conventional EL. Furthermore, the transducer was designed to be a wearable device that could be fixed to the holder, making it hands-free and thereby eliminating the problem of having a busy hand when speaking.

ヒト声帯の黄斑は幹細胞ニッチであり，黄斑に分布する細胞は組織幹細胞である可能性を報告してきた．in vitroで黄斑内の細胞を培養するとコロニーを形成して増殖する．本研究では，声帯黄斑（生体内，in vivo）内のコロニー形成とその微細構造を検討した．

対象は病変がないヒト成人の声帯5例である．方法はヒト声帯黄斑の細胞を電子顕微鏡下に，また免疫組織化学を用いて光学顕微鏡下に観察した．

細胞から分泌された無定形物質，糖タンパク質を介して，細胞同士が接近・接着し，細胞が集塊し，生体の声帯黄斑内でも細胞がコロニーを形成していた．免疫組織化学では糖タンパク質はE-カドヘリンと考えられた．接近した細胞は接着複合体（アドヘレンス結合，デスモゾーム様結合）を形成し，接着複合体を介して細胞同士が接触していた．

幹細胞はコロニーを形成して増殖するが，その機序と役割は不明な点が少なくない．ヒト声帯黄斑内の組織幹細胞はin vitroで培養した時のみならず，生体内（in vivo）の声帯黄斑（幹細胞ニッチ）でもコロニーを形成していることが確認された．

A laryngeal cleft is a rare congenital malformation of the posterior laryngeal or laryngotracheal wall with an incidence of ≦ 0.1%. Since it presents with symptoms of dysphagia, aspiration pneumonia, and hoarseness in early childhood, many patients with laryngeal clefts are often diagnosed in infancy. We herein report a rare case involving an adult patient with a typeⅡ-laryngeal cleft who underwent endoscopic repair and showed improvement in dysphagia. The characteristic findings on laryngeal endoscopy of this disease include enlargement of the inter-arytenoid region and redundant soft tissue overlying the arytenoid cartilages that prolapses into the cleft (ram sign) as well as a gap behind the vocal process during vocalization. Otolaryngologists need to be aware of this characteristic finding, since the disease is often overlooked.

Patients with head and neck cancer who undergo total laryngectomy often suffer from significant communication disorders due to permanent aphonia. While various substitutes for voice loss, including an electronic artificial larynx, tracheoesophageal shunt, esophageal speech, and written communication, have been currently employed to communicate against aphonia, few methods have used the voice of a preoperative patient. “Coestation^®” is a smartphone application that synthesizes patients’ voice and is now clinically applied to patients with amyotrophic lateral sclerosis (ALS). To verify whether this application has the potential to become a new substitute voice, we launched a clinical investigation for patients with head and neck cancer who were scheduled to undergo total laryngectomy. We preoperatively performed a voice synthesis using the smartphone application in two patients and postoperatively requested them to use an electronic artificial larynx and the synthesized voice. The patients stated that the synthesized voice was more similar to their original voice than the artificial larynx and were very satisfied about its voice quality. Based on these preliminary results, we plan to enroll more patients to assess the general usefulness of the synthesized voice as a new substitute voice.