Basic research involved in swallowing is critical not only for understanding the basic mechanisms underlying swallowing but also for making clinical advances in swallowing assessments and treatments in light of the aging of society. Animal models should be used to investigate the neuronal mechanisms underlying the generation of swallowing to help clarify the pathophysiological basis of dysphagia, particularly in the pharyngeal stage of swallowing. These neuronal networks are predominantly controlled by the swallowing central pattern generator (Sw-CPG) within the medulla by which the stereotyped and replicable movement of pharyngeal swallowing is generated. Previous studies have investigated brainstem mechanisms that control pharyngeal swallowing in various kinds of animals and experimental settings. In addition, an experimental model with an arterial perfused brainstem preparation has recently been preferred for analyzing the neuronal characteristics of swallowing interneurons as well as behavioral dynamics during swallowing. Further experiments are warranted to clarify the processing of neuronal signals within the Sw-CPG to facilitate the development of novel treatments for dysphagia.

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 vocal fold mucosa, including their stemness, asymmetric cell division, cellular hierarchy and lineage determination, was reviewed and summarized.

Regarding the stemness, the cells in the human maculae flavae have stemness and multipotency. Subcultured cells form a colony-forming unit. The cell features in the maculae flavae meet the minimal criteria defining mesenchymal stem cells. In addition, subcultured cells differentiate into ectoderm, mesoderm and endoderm. Cell divisions in the maculae flavae reflect asymmetric self-renewal in vitro. Regarding the heterogeneity and hierarchy of cells in the maculae flavae of the human adult vocal fold mucosa, three phenotypes of cells (cobblestone-like polygonal cells, vocal fold stellate cell-like cells possessing lipid droplets in the cytoplasm and fibroblast-like spindle cells) are present in the human adult maculae flavae. The cobblestone-like polygonal cells are at the top of the cellular hierarchy in the stem cell system. The lineage determination of the tissue stem cells has not yet been elucidated. The cells in the maculae flavae of the human adult vocal fold mucosa have heterogeneity and hierarchy in the stem cell system.

Contrast agent aspiration is an established complication of upper gastrointestinal and videofluoroscopic swallow studies (VFs). Barium sulfate (Ba) suspension is the most widely used contrast agent for VFs. The molecular biological mechanisms underlying acute and chronic responses to contrast agent (CA) aspiration in the respiratory organs remain unclear. We examined these mechanisms underlying the acute and chronic responses to three kinds of CA aspiration in the lung and studied the effects of different barium concentrations on the respiratory organs. Eight-week-old male Sprague Dawley rats were used for animal models of aspiration. We elucidated the mechanisms underlying these effects induced by CA aspiration, including Ba, ionic iodinated CA (ICA), and non-ionic iodinated CA (NICA). In the acute phase, Ba caused severe histopathologic changes and more prominent inflammatory cell infiltration in the lungs than the two other iodinated CAs. Increases in the expression of inflammatory cytokines were observed in the Ba and ICA aspiration rats. NICA did not cause any obvious histologic changes or the expression of inflammatory cytokines and fibrosis-related genes in the lungs. In the chronic phase, Ba particles remained after 30 days and caused histopathologic changes and inflammatory cell infiltration. Iodinated ICA and NICA did not result in any perceptible histologic changes. Furthermore, both low-Ba and high-Ba aspiration caused inflammatory cell infiltration in the lung at two days post aspiration with an increase in the expression of inflammatory cytokines. At 30 days post-aspiration, small quantities of barium particles remained in the lung of the low-Ba group without any inflammatory reaction. Chronic inflammation was recognized in the high-Ba group up to 30 days post aspiration. Ba caused significantly more acute and chronic lung inflammation in our rodent model than ICA or NICA. Aspirated Ba particles did not clear from the lung within one month and caused mild chronic pulmonary inflammation. Even with a small amount of low-concentration Ba aspiration (30% [w/v]), Ba particles can remain in the lung for over a month, causing sustained late effects. NICA did not cause any discernible inflammatory response in the lungs, suggesting it may be the safest contrast agent for VFs.

Swallowing is a vital function, and the clearance of the pharynx by deglutition, which removes matter at risk of being aspirated, and the respiratory phase patterns associated with deglutition are important for protecting the airways and lungs against aspiration.

We herein review the swallowing and respiratory phase patterns associated with deglutition during sleep in the aged.

During sleep, deglutition is extremely infrequent or absent for long periods of time in the aged. The deeper the sleep stage, the lower the mean deglutition frequency. Consequently, clearance of the pharynx and esophagus by deglutition is extremely reduced during sleep in the aged. Furthermore, respiratory phase patterns associated with deglutition display adverse patterns during sleep in the aged.

Regarding aged individuals with obstructive sleep apnea, swallowing following and/or followed by inspiration, which is observed a great deal before CPAP (continuous positive airway pressure) therapy, is markedly reduced during CPAP therapy. However, swallowing following and/or followed by expiration is markedly increased during CPAP therapy. Respiratory phase patterns associated with sleep-related deglutition are improved under CPAP therapy.

Due to the complexity of the swallowing process, many adverse health conditions can influence the swallowing functions during sleep in the aged. Sleep-related deglutition and respiratory phase patterns may adversely influence aspiration-related diseases, such as aspiration pneumonia, especially in the aged, not only in cases of primary presbyphagia but also those of secondary presbyphagia as well.

The high-pitched blowing exercise is a technique for conducting water resistance with high-pitch voice. This exercise is one of semi-occluded vocal tracts (SOVTE). When we performed high-pitched blowing through a laryngoscope in cases where high-pitched vocalization was difficult, the interval of posterior glottis disappeared, and the voice function also improved.

We conducted a detailed examination of the voice pitch for water resistance. The subjects were 40 healthy young women currently attending our school (age: 19-22 years old), randomly divided into 4 groups: Silent Group, Speaking Voice Group, Chest Voice Group, and Head Voice Group. The examination items were the duration of water resistance before/after training, maximum phonation time (MPT), phonatory function test, physiological voice range, acoustic analysis, and subjective evaluation. As an additional study, we also measured the open quotient (OQ) by a photoglottogram (PGG). We observed no marked changes in the Silent Group before/after training. Regarding the phonatory function test findings,were recognized improvement in the MPT, amplitude perturbation quotient, harmonics-to-noise ratio, and voice handicap index. For the PGG, 25% OQ indicated a favorable level in the Head Voice Group. These findings suggested that the high-pitched blowing exercise was more effective than ordinary water resistance for voice disorder.

Voice therapy is a tool for treating voice disorders in singers. It has been widely accepted as a valid method for improving singing voice disorders worldwide. However, despite its wide acceptance for singers with dysphonia, little research exists to support the utility of voice therapy for singers with dysphonia as an intervention with measurable treatment outcomes. A forward focused voice has long been used in voice clinics throughout the world as a therapeutic approach for singers and nonsingers with dysphonia to reduce excessive tension on the vocal tract and facilitate a resonant voice quality and vocal fold vibration. However, the effects of a forward focused voice in singers compared to nonsingers with dysphonia have not been sufficiently evaluated. The current review evaluated the vocal tract function and voice quality in singers and nonsingers with dysphonia after undergoing therapy with a forward focused voice.

Although it is generally accepted that phonomicrosurgery may be indicated for vocal fold mass lesions even in professional singers, the specific indications for surgery on stroboscopic findings for microlesions of the vocal folds in professional singers are not clear. The present study included 88 patients (male, n=36; female, n=52) who presented to the AKASAKA Voice Health Center with clear complaints in singing and who underwent phonomicrosurgery to resect microlesions of the vocal folds. At three months postoperatively, 102 of the total 117 subjective complaints in singing were resolved (87%). We classified five vertical locations of lesions (determined based on surgical findings) on the medial surface of the vocal folds, and statistically analyzed the differences in verticality according to the various attributes of the cases. The results showed that lesions were significantly more prevalent in the upper part of the vocal folds when the singing or disordered voice was in a high pitch and light register, while lesions were significantly more prevalent in the lower part of the vocal folds when the voice was in a low pitch and heavy register. Considering laryngeal regulation during singing, we hypothesize that lesions in the lower part of the mucosal wave-generating area are more likely to cause a malfunction in singing. A lesion in such a location can also be identified by stroboscopy, as a prominence on the medial margin in the closing phase (lesion on lower crest: LLC). Although individualized treatment is necessary, stroboscopic findings that demonstrate the presence of an irreversible LLC in singing may be a good indication for phonomicrosurgery.

Transoral robotic surgery using the da Vinci surgical system has become a viable treatment options for small primary oropharyngeal, hypopharyngeal, and supraglottic cancers. Recently, various clinical trials have been conducted around the world. In addition to its usage in the above field, transoral robotic surgery has also been applied to sleep apnea syndrome treatment and locally advanced cancer dissection with reconstructive surgery. However, despite the fact that roughly 10 years have passed since the introduction of robotic surgery support equipment in Japan, operations in the head and neck area have remained outside of insurance coverage. Last year, approval of the device for head and neck cancer treatment was finally granted, and a training program was established. The number of surgical facilities and cases treated by transoral robotic surgery is now on the rise. It is a promising treatment in Japan, and insurance coverage should be applied promptly. In addition, although the robotic equipment at present is used for laparoscopic surgery, endoscopic type robot is suitable for the head and neck region is expected to be developed in the future. Close attention should be paid to future device development.

Laryngeal cancer management must maintain a balance between improving the survival while preserving the function. Chemoradiotherapy has become the standard of care for larynx preservation in advanced laryngeal cancers. Recent data have shown faltering survival trends for patients with laryngeal cancer, calling for improvement through innovation. As chemoradiotherapy has been the prevailing management over the past two decades, cases receiving open laryngeal surgery have decreased. With contemporary trends toward minimally invasive surgery, it is imperative that head and neck surgeons improve partial laryngectomy procedures using recent medical innovations. Since 2016, our international collaboration team has conducted trials focused on blending transoral surgeries with conventional open laryngectomies. An innovative hybrid approach by blending transoral robotic surgery or endoscopic transoral surgery with limited open (6-cm skin incision) supracricoid partial laryngectomy may facilitate postoperative and functional recoveries. Head and neck surgeons are in an important position for improving partial laryngeal surgeries, which may offer survival benefits with functional improvements.

Chronic cough, which persists for more than eight weeks, results in a significant impairment of the quality of life. The JRS Guidelines for the Management of Cough and Sputum 2019 shows the diagnostic algorithms for chronic cough. However, some patients with chronic cough seem to have an unknown etiology, making them difficult to treat. Since the larynx plays a crucial role in protecting the lower airway from aspiration via coughing, the laryngopharynx is a sensitive organ. Therefore, laryngopharyngeal reflux (LPR), even when receiving proton pump inhibitor (PPI) therapy, can cause coughing. Because LPR disease (LPRD) is not easy to diagnose, it is important to measure LPR using hypopharyngeal multichannel intraluminal impedance pH metry (HMII) for patients with chronic cough of unknown etiology. We showed that 73% of patients with chronic cough were diagnosed with LPRD, and 73% of those with chronic cough diagnosed with LPRD became asymptomatic after antireflux surgery. LPRD should be distinguished from chronic cough of unknown etiology.

Previous epidemiological studies have indicated that bilateral vocal fold palsy (BVFP) is the most common cause of bilateral vocal fold immobility (BVFI), followed by posterior glottic stenosis (PGS) due to ankylosis of the cricoarytenoid joint, fixation and/or fibrosis at the posterior glottis. The differential diagnosis between BVFP and PGS is made based mainly on careful clinical history-taking, fiberscopic observation of the subglottal region through the tracheostoma, and performance of electromyography. Based on the our clinical findings of adducted-type BVFI thus far, we have suggested treatment options and a severity classification system of BVFI that focuses mainly on electromyography results for assessing dynamic restenosis and traction-mobility test results for assessing static restenosis. Both the surgical techniques of laser subtotal arytenoidectomy and laterofixation are effective and useful for widening the glottis in cases of BVFI. However, the deterioration of the voice quality in laser subtotal aryteenoidectomy is less marked than with laterofixation.

The present study clarified the swallowing-related neural activities using human intracranial electrodes. Eight epileptic participants fitted with intracranial electrodes on the orofacial cortex were asked to swallow a water bolus, and cortical oscillatory changes were investigated. High γ (75-150 Hz) power increases associated with swallowing were observed in the subcentral area. To decode swallowing intention, ECoG signals were converted into images whose vertical axes were the electrode’s contacts and whose horizontal axis was the time in milliseconds; these findings were used as training data. Deep transfer learning was carried out using AlexNet, and the power in the high-γ band was used to create the training image set. The accuracy reached 74%, and the sensitivity reached 83%. We showed that a version of AlexNet pre-trained with visually meaningful images can be used for transfer learning of visually meaningless images made up of ECoG signals. This study demonstrated that swallowing-related high γ activities were observed in the subcentral area, and deep transfer learning using high γ activities enabled us to decode the swallowing-related neural activities.

Tracheoesophageal shunt utterance using a voice prosthesis as a substitute voice after laryngectomy is an excellent method and is widely used. However, in addition to temporary removal due to complications, the use of voice prostheses is occasionally discontinued for various reasons that lead to their permanent removal. We evaluated the voice acquisition rate, complications, and outcomes of 23 patients who underwent voice reconstruction using a voice prosthesis after total laryngectomy in our department from January 2007 to December 2018. The voice acquisition rate was 87%. Seven complications occurred in six cases, the most common of which was granulation, followed by leakage and infection in one case each, although all were eventually rescued. However, there were five cases where permanent voice prosthesis removal was necessary for reasons other than complications. Three of these patients had good voice acquisition but were unable to use the voice prosthesis due to the effects of other diseases. In the other two cases, a voice could not be obtained, and the patients expressed their desire to have the prosthesis removed. In the future, aging of voice prosthesis users and long-term use are expected, which will make it necessary not only to accurately determine the adaptation in consideration of the patient’s intention, activity and living environment but also to consider how to proceed when voice prosthesis use becomes difficult due to other diseases.

Computed tomography is useful for diagnosing laryngeal trauma, the extension of laryngeal cancer and lymph node metastasis of carcinoma. Yumoto et al. reported that helical CT was useful for evaluating three-dimensional images of the laryngeal structure. Furthermore, they performed helical CT in patients with unilateral vocal fold paralysis in order to understand the laryngeal morphology. Hiramatsu et al. reported that this approach visualized the movement of the arytenoid cartilages on reconstruction imaging.

The present study evaluated six patients with unilateral vocal fold paralysis whose voices improved after phonosurgery. Two patients underwent arytenoid adduction and thyroplasty typeⅠ, two underwent only thyroplasty typeⅠ, and two underwent injection surgery. The virtual endoscopic images reconstructed from ultra-high-resolution CT (UHRCT) showed a gap in the posterior glottal region in the cases for whom preoperative evaluations using flexible laryngoscopy had been very difficult due to supraglottic hypertension. Postoperative changes in the arytenoid position were observed on three-dimensional images.

UHRCT was shown to be effective for selecting the phonosurgery approach. This modality is a very important tool for determining which phonosurgical procedures to perform and for evaluating the postoperative change. We successfully evaluated the anatomical changes, glottal closure and position of arytenoid cartilages pre- and postoperatively using UHRCT.

Posterior glottic, subglottic and tracheal stenoses are uncommon delayed complications of burn and inhalation injury. The treatment varies based on the individual severity, but some patients need permanent tracheostomy. A 38-year-old-man with a tracheostomy after burn and inhalation injury four years ago had undergone Ejinell’s laterofixation three times. He still had narrowing of the airway due to bilateral vocal fold immobility. We diagnosed the immobility as having caused the posterior glottic stenosis. Bilateral Ejinell’s laterofixation was performed, and the buccal mucosa was grafted to avoid scarring. The patient successfully underwent decannulation.

Varicella-zoster virus (VZV) reactivation is known to rarely cause inferior cranial nerve paralysis with symptoms such as pharyngeal pain, hoarseness, and dysphagia. We herein report 5 cases involving patients with laryngeal paralysis caused by VZV reactivation, in which the diagnosis was confirmed by a serological analysis. The symptoms of the five patients included pharyngeal pain (n=4), hoarseness (n=3), and dysphagia (n=3). The 5 patients were treated with acyclovir (750 mg/day) for 7 days and intravenous steroids; all patients were cured and achieved complete relief from their symptoms after various periods of time.

Among the 69 patients with laryngeal paralysis caused by VZV that were reported in the relevant Japanese literature (including our 5 patients), 53 of the 56 patients (95%) showed symptoms of sore throat, hoarseness, or dysphagia. Vagal (X), glossopharyngeal (Ⅸ), facial (Ⅶ) and hypoglossal (Ⅻ) nerve paralysis was reportedly observed in 69 (100%), 56 (81%), 30 (43%) and 6 (7%) of the 69 patients, respectively. Forty-nine (71%) of the 69 patients were treated with the combination of acyclovir and steroids, and 52 (75%) patients with laryngeal paralysis were cured.

In consideration of our 5 patients and the 64 patients reported in the relevant literature, in cases in which symptoms such as pharyngeal pain, hoarseness, and dysphagia, and findings of erythema and laryngeal paralysis are not found simultaneously, careful and frequent endoscopic observation could lead to an early diagnosis and appropriate treatment of laryngeal paralysis caused by VZV.

The validity of the application of the Cepstral/Spectral Index of Dysphonia (CSID) to Japanese dysphonic speech was examined by analyzing normal and breathy voice samples both produced by healthy Japanese volunteers with no vocal problems. Four Japanese sentences which had phonological similarities to the English test sentences were prepared for the application of the CSID. The voice samples included sustained vowel /a/ and the four sentences.

The CSID was applied for analyzing both the sustained vowel and the four sentences. Established indices based on pitch synchronous analyses, such as period perturbation quotient (PPQ), amplitude perturbation quotient (APQ) and noise to harmonic ratio (NHR) were applied to the samples of the sustained vowel.

For the grade of the hoarseness and the breathiness, auditory perceptual evaluations of Japanese speech sentences and the sustained vowel were performed using a visual analog scale (VAS). GRBAS scale was used for evaluations of the sustained vowel only.

Strong statistical relationships were found between the CSID and the three indices with pitch synchronous analyses. Furthermore, the CSID had strong statistical relationships with the two auditory perceptual evaluations as well, which was equal to relationships between the auditory perceptual evaluations and the indices with pitch synchronous analyses. Given that the CSID can be used to analyze speech samples whereas the indices with pitch synchronous analysis have certain technical problems to analyze speech samples, this index is considered to be applicable as a useful measure for evaluating vocal dysfunction of Japanese speech and should be used actively in clinical settings.

Endotracheal intubation can induce various laryngeal injuries. Treatments for such injuries differ depending on the injured site and duration elapsed after intubation. We herein report two cases of laryngeal injury due to endotracheal intubation that required surgical treatment. Case 1 was an 80-year-old woman who suffered from dyspnea 2 days after surgery for lung cancer. She had been intubated with a thick, double-lumen endotracheal tube, and had exhibited persistent hoarseness since the surgery. Upon laryngeal endoscopy, her airway had almost completely closed due to membranous granulation covering the subglottis. Tracheostomy, removal of the granulation tissue, and local injection of triamcinolone acetonide were performed to secure the airway. Although several rounds of granulation tissue removal were required to achieve a safe airway, the tracheostoma was ultimately successfully closed. Case 2 was a 55-year-old man who had been intubated for 11 days after surgery for esophageal cancer. Hoarseness was evident immediately after extubation. Laryngeal endoscopy confirmed bilateral vocal fold paralysis at the paramedian position, but the airway was narrowly maintained. During follow-up, vocal fold mobility gradually improved for a time. However, bridge-like granulation appeared in the posterior glottis later, and vocal fold abduction gradually became impaired bilaterally. Removal of the granulation tissue and topical triamcinolone acetonide injection were performed to prevent scar formation. After the surgery, the vocal fold mobility fully recovered without recurrence of granulation tissue.

Laryngeal injuries should be suspected when hoarseness is apparent after extubation, and surgical treatment should be considered in cases involving airway problems.

Nasogastric tube syndrome (NGTS) is a rare syndrome that causes abduction dysfunction in both vocal folds after gastric tube insertion, and the clinical condition is poorly understood.

We herein report a case of NGTS treated with larynx electromyography. An 89-year-old woman suddenly presented with stridor and dysphagia during medical treatment for ileus. Although the patient had a history of left vocal fold palsy of the paramedian position after aortic surgery, the right vocal fold was located medially and slightly dysfunctional, and the bilateral arytenoid regions were swollen on flexible larynx endoscopy. Because of the high glottic stenosis, emergency tracheostomy was performed. Two days later, the right vocal fold began to gradually move, and this motion improved substantially one week later. Therefore, she was diagnosed with NGTS. Larynx electromyography reduced the interference pattern in the right thyroarytenoid muscle. Neuroparalysis was also suggested as a pathosis of NGTS.