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OBJECTIVES: This study was undertaken to identify the types of collagen fibrils in the extracellular matrix of the human vocal fold lamina propria. METHODS: Human vocal folds were obtained from 3 autopsy cases less than 65 years of age. The vocal fold specimens were labeled by primary antibodies of anti-type I and anti-type III collagens, and then by secondary antibody conjugated with 15 nm colloidal gold. The specimens were observed with a scanning electron microscope. Secondary electron imaging and backscatter electron imaging of high-resolution field emission scanning electron microscopy were used to detect gold particles indicating immunolabeling. RESULTS: Type III collagen-labeling gold particles were abundant on the fibrils constructing collagenous fibers, whereas type I collagen-labeling gold particles were sparsely present on fibrils in collagenous fibers. A few reticular fibers were labeled by both collagen type I and collagen type III. CONCLUSIONS: The results suggest that collagen type I coexists with collagen type III in fibrils of both collagenous fibers and reticular fibers. [ABSTRACT FROM AUTHOR]

Objective-Since 1990, we have performed steroid injections into the vocal fold under topical anesthesia using fiberoptic laryngeal surgery (FLS) in an outpatient clinic. The aim of this study was to retrospectively assess the usefulness of this treatment method in 44 patients with mild Reinke's edema. Material and Methods-Using fiberoptic monitoring of the larynx, a curved injection needle was inserted via the oral cavity and triamcinolone acetonide was injected into Reinke's space of the bilateral vocal fold. Results Remission or improvement was observed in almost all patients in terms of both patients' self-rating of hoarseness and endoscopic vocal fold findings. The maximum phonation time was a mean of 9.0 s before operation and 11.4 s after operation, and this increase was significant (p < 0.01). Voice pitch also improved, from 168 to 181 Hz, in female patients, and this increase was also significant (p < 0.05). Conclusion-Steroid injection is considered to be useful for treating mild Reinke's edema. [ABSTRACT FROM AUTHOR]

The pathophysiology of laryngopharyngeal reflux (LPR) and its impact on the vocal fold is not well understood, but may involve acid damage to vocal fold barrier functions. Two different components encompass vocal fold barrier function: the mucus barrier and tight junctions. Mucus retained on epithelial microprojections protects the inside of the vocal fold by neutralizing acidic damage. Tight junctions control permeability between cells. Here we developed an in vitro experimental system to evaluate acidic injury and repair of vocal fold barrier functions. We first established an in vitro model of rat vocal fold epithelium that could survive at least one week after barrier function maturation. The model enabled repeated evaluation of the course of vocal fold repair processes. Then, an injury experiment was conducted in which vocal fold cells were exposed to a 5-min treatment with acidic pepsin that injured tight junctions and cell surface microprojections. Both of them healed within one day of injury. Comparing vocal fold cells treated with acid alone with cells treated with acidic pepsin showed that acidic pepsin had a stronger effect on intercellular permeability than acid alone, whereas pepsin had little effect on microprojections. This result suggests that the proteolytic action of pepsin has a larger effect on protein-based tight junctions than on phospholipids in microprojections. This experimental system could contribute to a better understanding of vocal fold repair processes after chemical or physical injuries, as well as voice problems due to LPR pathogenesis., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Masanobu Mizuta, Ichiro Tateya reports financial support was provided by Japan Society for the Promotion of Science. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Over the last decade, novel anticancer drugs have improved the prognosis for recurrent or metastatic squamous cell carcinoma of the head and neck (RM-SCCHN). However, this has increased healthcare expenditures and placed a heavy burden on patients and society. This study investigated the frequency of use and costs of select palliative chemotherapy regimens in Japan., Methods: From July 2021 to June 2022 in 54 healthcare facilities, we gathered data of patients diagnosed with RM-SCCHN and who had started first-line palliative chemotherapy with one of eight commonly used regimens. Patients with nasopharyngeal carcinomas were excluded. The number of patients receiving each regimen and the costs of each regimen for the first month and per year were tallied., Results: The sample comprised 907 patients (674 were < 75 years old, 233 were ≥ 75 years old). 330 (36.4%) received Pembrolizumab monotherapy, and 202 (22.3%) received Nivolumab monotherapy. Over 90% of patients were treated with immune checkpoint inhibitors as monotherapy or in combination with chemotherapy. Treatment regimens' first-month costs were 612 851-849 241 Japanese yen (JPY). The cost of standard palliative chemotherapy until 2012 was about 20 000 JPY per month. The incremental cost over the past decade is approximately 600 000-800 000 JPY per month, a 30- to 40-fold increase in the cost of palliative chemotherapy for RM-SCCHN., Conclusion: First-line palliative chemotherapy for RM-SCCHN exceeds 600 000 JPY monthly. Over the last decade, the prognosis for RM-SCCHN has improved, but the costs of palliative chemotherapy have surged, placing a heavy burden on patients and society., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Transoral robotic surgery (TORS), introduced by Weinstein et al. in 2005, has been widely adopted as a minimally invasive procedure, particularly for the treatment of patients with early stage oropharyngeal cancer. TORS is typically performed using the da Vinci Surgical System, similar to robot-assisted surgeries for other malignancies. The main difference between TORS and these other robot-assisted surgeries is that it is performed through the natural orifice of the mouth, which limits the surgical working space, and that it progresses from the lumen of the pharynx to the deeper tissues. The advantages of TORS are mainly due to the benefits of using the da Vinci Surgical System, such as three-dimensional high-definition images, magnification, multiple forceps articulation, tremor-stabilization function and motion scale function. To date, many big data and meta-analyses have shown that TORS is superior to conventional surgeries, such as open surgery, in terms of oncological outcomes, post-operative functionality and quality of life. In Japan, TORS is expected to spread across the country, as it has been covered by health insurance since April 2022. This review highlights the procedures of TORS, its unique aspects, its unparalleled advantages as a minimally invasive surgery for treating laryngeal and pharyngeal cancers, and its current status in Japan., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: The application of the da Vinci Surgical System in neurosurgery is limited due to technical difficulties requiring precise maneuvers and small instruments. This study details the advantages and disadvantages of robotics in neurosurgery and the reachable range of the transoral approach to lesions of the skull base and upper cervical spine., Methods: In a cadaver study, the da Vinci Xi robot, lacking haptic feedback, was utilized for sagittal and coronal approaches on 5 heads, facilitating dura suturing in 3, with a 30°-angled drill for bone removal., Results: Perfect exposure of all the nasopharyngeal sites, clivus, sellar, and choana, including the bilateral eustachian tubes, was achieved without any external incisions using this palatal split approach of transoral robotic surgery. The time required to perform a single stitch, knot, and complete single suture in robotic suturing of deep-seated were significantly less compared to manual suturing via the endonasal approach., Conclusion: This is the first report to show the feasibility of suturing the dural defect in deep-seated lesions transorally and revealed that the limit of reach in the coronal plane via a transoral approach with incision of the soft palate is the foramen ovale. This preclinical investigation also showed that the transoral robotic approach is feasible for lesions extending from the sellar to the C2 in the sagittal plane. Refinement of robotic instruments for specific anatomic sites and future neurosurgical studies are needed to further demonstrate the feasibility and effectiveness of this system in treating benign and malignant skull base lesions.

Background: We aimed to define the indications for sentinel lymph node biopsy (SLNB), the third option for cervical treatment in oral cancer with negative cervical lymph nodes., Methods: The greatest depth of invasion (DOI) and long diameter (LD) of the primary site were used as exposures. SLN metastasis was considered the outcome., Results: In three trials conducted between 2009 and 2016, 158 patients were eligible and reassigned to this study group. The scatterplot based on the respective values of DOI and LD would eventually be divided into three sections. In cases of sections T1, T2, and T3, the proportions of SLN metastasis positivity were 21.3%, 35.3%, and 51.2%, respectively. In certain cases of T1 with 2 mm < DOI ≤ 5 mm and 8 mm < LD ≤ 20 mm, the proportion of SLN metastasis positivity was 40.9%., Conclusions: SLNB-navigated or assisted neck dissection can be added as an effective procedure for N0 neck control., (© 2023 Wiley Periodicals LLC.)

In this study, we report a case of tracheotomy using the ex utero intrapartum treatment (EXIT) procedure in a fetus that was pointed out as having bilateral giant cervical cysts at prenatal diagnosis and whose postnatal airway occlusion was predicted. The subject was a female aged 35. She was diagnosed with polyhydramnios at 28 weeks of pregnancy. The fetus was found to have a giant cervical cyst before she was referred to the department of obstetrics and gynecology of our hospital. On the second day of 37 weeks of pregnancy, oral tracheal intubation was attempted on the fetus using the EXIT procedure after the caesarean operation, but intubation was difficult resulting in a tracheotomy. The oxygenation of the fetus during the operation was maintained well without any postoperative complication. Postnatal fetal airway occlusion is a critical incident which may lead to the death of a fetus. It was assumed, however, that the airway management under the same procedure was completed by the preoperative detailed simulation with the staff of the departments of anesthesiology, obstetrics and gynecology and pediatrics as well as the operating room personnel., Competing Interests: There is no conflict-of-interest to be disclosed concerning this article.

There are many methods and types of equipment for measuring the nasal airway, but there is no consensus regarding the results of various clinical studies on nasal obstruction. In this review, we discuss the two major methods of objectively assessing the nasal airway: rhinomanometry and acoustic rhinometry. The Japanese standard of rhinomanometry in Japanese adults and children was established by the Japanese Standardization Committee on Rhinomanometry in 2001 and 2018, respectively. However, the International Standardization Committee has proposed different standards because of differences in race, equipment, and social health insurance systems. The standardization of acoustic rhinometry in Japanese adults is making progress in several Japanese institutes, but the international standardization of acoustic rhinometry has not yet begun. Rhinomanometry is the physiological expression of nasal airway breathing, whereas acoustic rhinometry is the anatomic expression. In this review, we introduce the history and methods of the objective assessment of nasal patency and the physiological and pathological issues regarding nasal obstruction., Competing Interests: The authors declare that they have no conflict of interest.

Background: Endoscopic laryngopharyngeal surgery (ELPS) is a minimally invasive transoral surgery for superficial pharyngeal and laryngeal cancer, but dysphagia occasionally occurs post-treatment. We investigated dysphagia following ELPS and its risk factors., Methods: Of the 145 patients who underwent ELPS, 92 were evaluated in this study using the Hyodo score, Functional Outcome Swallowing Scale, Eating Assessment Tool-10 along with the total scores for the three items of the method of intake, time, and food preoperatively and on postoperative 1, 3, and 6 months. We examined the 6-month trends of these values. Furthermore, the fasting period post-surgery, the need for swallowing rehabilitation by a speech therapist, and postoperative pneumonia episodes were set as outcomes reflecting the short-term swallowing function. We determined the associations between these outcomes and patient background factors., Results: Postoperatively, the Hyodo score worsened at 1 month but recovered at 3 months. The Hyodo scores of all patients who underwent postcricoid ELPS did not worsen. The diameter of the resected specimen (DRS) was significantly associated with the need for swallowing rehabilitation and postoperative fasting time. A DRS ≥ 35 mm was considered the threshold for the need of swallowing rehabilitation, postoperative pneumonia, and prolonged postoperative fasting time., Conclusion: ELPS exerts a temporal and limited impact on the swallowing function, which recovers within 3 months in every swallowing evaluation. This necessitates additional care during the treatment of patients with mucosal defects ≥ 35 mm, owing to the significant association between the DRS and short-term swallowing function., (© 2023. The Author(s) under exclusive licence to Japan Society of Clinical Oncology.)

Objectives: Intraoperative cone beam computed tomography (CBCT) imaging has the potential to facilitate the surgical procedure. The current preliminary retrospective chart review investigated the benefits of intraoperative CBCT during laryngoplasty., Method: This study examined 26 cases that underwent intraoperative CBCT imaging during laryngoplasty, with one patient who counted twice due to first and revision surgery. The visual quality of structures of interest (glottal shape, thyroid cartilage, arytenoid cartilage, and implants) was determined using intraoperative CBCT during laryngoplasty. Each patient also underwent an aerodynamic assessment., Results: CBCT provided unique information, such as surgical landmarks in severe scarring, the subglottal shape, and the rotation angle of the arytenoid cartilage during arytenoid adduction. Nonetheless, 26.9% (7 of 26) of cases were affected by motion artifact, due to the long acquisition time. When motion artifact-negative cases were evaluated, 100% of glottal shape and more than 89% of thyroid cartilage were well visualized. All arytenoids were well-visualized in patients ≥ 50 years of age and without motion artifact, while CBCT failed to visualize the arytenoids in 2 of 4 patients who were < 50 years, due to the lack of calcifications. After medialization surgery, the yields of improved maximal phonation times (MPTs) in the motion artifact-negative and -positive groups were 8.7 sec and 3.4 sec, respectively (p = 0.032; Welch's t test). This comparison indicates intraoperative CBCT would contribute in MPT improvement, if CBCT is taken in measurable quality., Conclusion: The potential benefits of intraoperative CBCT during laryngoplasty were demonstrated. A corollary, prospective study is warranted to further confirmation., Competing Interests: Declaration of Competing Interest All authors participated have no financial support or relationship that causes a conflict of interest. The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions., (Copyright © 2022. Published by Elsevier B.V.)

Introduction: Radiation-induced carotid artery stenosis (RI-CS) is known as one of long-term side effects of radiotherapy for head and neck cancer (HNC). However, the clinical time course after irradiation has been poorly understood. We aimed to investigate the natural history of radiation-induced carotid atherosclerosis, comparing the patients who received radiotherapy for HNC with the patients who were treated without radiotherapy., Methods: The patients who received treatment of HNC at Department of Otolaryngology, Head and Neck Surgery of Kyoto University Hospital, from November 2012 to July 2015 were enrolled. The patients were assigned into the RT group and the control group, depending on whether radiotherapy was planned or not. Annual carotid ultrasound was performed from the enrollment to 5 years. The increase of mean intima-media thickness (IMT) at common carotid artery from the enrollment (Δmean IMT) was evaluated., Results: Fifty-six patients in the RT group and 25 patients in the control group were enrolled. From 5-year follow-up data, the significant higher increase of Δmean IMT was consistently observed in the RT group than in the control group after 2 years. The RT group presented a 7.8-fold increase of mean IMT compared to the control group (0.060 mm per year in the RT group and 0.008 mm per year in the control group). Cumulative incidence curves obtained from the analysis of all vessels revealed that the RT group presented higher incidence of Δmean IMT ≥0.25 mm than the control group (p < 0.01). In the RT group, the patients with mean IMT ≥1.0 mm at enrollment exhibited significantly higher incidence of Δmean IMT ≥0.25 mm than the patients with mean IMT <1.0 mm (p < 0.01)., Discussion: Radiotherapy for HNC induces continuous carotid mean IMT progression. The irradiated carotid arteries with mean IMT ≥1.0 mm before radiotherapy presented earlier IMT progression than those with mean IMT <1.0 mm., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

Objectives: The success of type 2 thyroplasty (TP2) for adductor spasmodic dysphonia (AdSD) depends on the selection of optimally sized titanium bridges, which requires accurate assessment of intraoperative vocal changes. While this procedure has traditionally been performed according to the laryngologist's experience, the most appropriate method for voice monitoring and selection of titanium bridge size remains to be determined. This study aimed to investigate evaluation parameters useful for voice monitoring, as these may allow less experienced surgeons to perform TP2 properly., Methods: In this prospective study, voice monitoring was performed in 18 patients with AdSD patients undergoing TP2. Evaluations were performed preoperatively, intraoperatively, 13 weeks postoperatively, and 52 weeks postoperatively using GRBAS (grade, roughness, breathiness, asthenia, and strain), as well as perceptual judgment and acoustic analyses., Results: Preoperative and intraoperative assessments of the G, R, B, and S parameters, perceptual judgment, and harmonic-to-noise ratio (HNR) were in moderate or better agreement. Intraoperative and 13- or 52-week postoperative measurements of the R, B, and G parameters and strangulation, tremor, and HNR were also in high agreement. When two different sizes of titanium bridges were compared (unselected vs. selected), ratings for G, R, S, strangulation, tremor, jitter, shimmer, HNR, standard deviation of F0, and degree of voice breaks were better for the selected width than the unselected width., Conclusion: The candidate items for intraoperative voice monitoring during TP2 for AdSD are G, R, strangulation, tremor, and HNR. The use of these items may help to ensure successful TP2 and contribute to the advancement of laryngeal framework surgery., Level of Evidence: Level 4., Competing Interests: The authors have no conflicts of interest directly relevant to the content of this article., (© 2022 The Authors. Laryngoscope Investigative Otolaryngology published by Wiley Periodicals LLC on behalf of The Triological Society.)

Objective: Some patients with cleft palate (CP) need secondary surgery to improve functionality. Although 4-dimensional assessment of velopharyngeal closure function (VPF) in patients with CP using computed tomography (CT) has been existed, the knowledge about quantitative evaluation and radiation exposure dose is limited. We performed a qualitative and quantitative assessment of VPF using CT and estimated the exposure doses., Design: Cross-sectional., Setting: Computed tomography images from 5 preoperative patients with submucous CP (SMCP) and 10 postoperative patients with a history of CP (8 boys and 7 girls, aged 4-7 years) were evaluated., Patients: Five patients had undergone primary surgery for SMCP; 10 received secondary surgery for hypernasality., Main Outcome Measures: The presence of velopharyngeal insufficiency (VPI), patterns of velopharyngeal closure (VPC), and cross-sectional area (CSA) of VPI was evaluated via CT findings. Organ-absorbed radiation doses were estimated in 5 of 15 patients. The differences between cleft type and VPI, VPC patterns, and CSA of VPI were evaluated., Results: All patients had VPI. The VPC patterns (SMCP/CP) were evaluated as coronal (1/4), sagittal (0/1), circular (1/2), and circular with Passavant's ridge (2/2); 2 patients (1/1) were unevaluable because of poor VPF. The CSA of VPI was statistically larger in the SMCP group ( P = .0027). The organ-absorbed radiation doses were relatively lower than those previously reported., Conclusions: Four-dimensional CT can provide the detailed findings of VPF that are not possible with conventional CT, and the exposure dose was considered medically acceptable.

As the laryngopharynx is closely related to swallowing, speech, and phonation, it is necessary to consider not only disease control but also a minimally invasive approach for the treatment of laryngopharyngeal cancer. Transoral surgery has been reported to be a minimally invasive method for treating these diseases. Transoral videolaryngoscopic surgery (TOVS) and endoscopic laryngo-pharyngeal surgery (ELPS) have been developed in Japan and recently emerged as treatments for patients with early stage pharyngeal and laryngeal cancers. However, securing an appropriate field of view and a narrow operating space during TOVS or ELPS are critical issues to be resolved for these surgeries. The clinical significance and safety of transoral robotic surgery (TORS) using the da Vinci Surgical System have been widely reported to provide surgeons with increased visualization and magnification, resulting in precise surgical margins and rapid functional recovery. In this context, a multi-institutional clinical study was conducted to evaluate the treatment outcomes of TORS for the treatment of laryngopharyngeal cancer in Japan, and the da Vinci Surgical System for oral robot-assisted surgery for these diseases was approved by the Pharmaceutical Affairs Agency in August 2018. This review provides an overview of the therapeutic effects of TOVS, ELPS, and TORS, with a particular focus on these therapeutic results in Japan., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Sano, Shimizu, Tateya, Fujiwara, Kishimoto, Maruo, Fujimoto, Mori, Kato, Tsukahara and Oridate.)

Purpose: Auditory-perceptual evaluation is essential for the assessment of voice quality. The Consensus Auditory-Perceptual Evaluation of Voice (CAPE-V) provides a standardized protocol and assessment form for clinicians to analyze the voice quality and has been adapted into several different languages. The aims of this study were to develop the Japanese version of the CAPE-V and to investigate its reliability and validity., Method: The Japanese CAPE-V consisted of the same three speech contexts (vowels, sentences, and conversation) as developed in the original English version. The sentences were designed according to the concepts of the original version and reviewed by Japanese phoneticians. To validate the usefulness of the Japanese CAPE-V, voices of 173 Japanese-speaking subjects (76 subjects with dysphonia and 97 without voice complaints) were evaluated by five experienced judges, according to the Japanese CAPE-V as well as the GRBAS (Grade, Roughness, Breathiness, Asthenia, Strain) scale., Results: The Japanese CAPE-V provided a high interrater reliability (intraclass correlation coefficients [ICCs] > .85 for all the parameters) as well as a high intrarater reliability (ICCs > .85 for all the parameters). In addition, overall severity, roughness, and breathiness in the Japanese CAPE-V were highly correlated with the corresponding dimensions in the GRBAS scale, having Spearman correlation coefficients greater than .8., Conclusion: This study demonstrated the reliability and validity of the newly developed Japanese CAPE-V as an auditory-perceptual evaluation instrument.

Tissue-engineered tracheae have been developed to replace defective tracheae. However, the direction of ciliated cells in the regenerated epithelium remains unclear. We investigated planar polarity formed in the regenerated airway epithelium after tracheal graft implantation. We partially resected the rat trachea and implanted a collagen scaffold. The direction of the basal foot was assessed by transmission electron microscopy. Immunofluorescence staining was performed to examine the biased distribution of Vangl1 and Frizzled6 proteins. The direction of mucociliary transport was analyzed by video microscopy. Our results showed that the basal feet of cilia in the proximal and distal regions of the implanted areas were respectively oriented toward the proximal and distal directions. The biased distribution of Vangl1 and Frizzled6, and the directions of mucociliary transport showed that planar polarities formed in the regenerated epithelium were oriented toward the proximal, distal, left, and right directions in the proximal, distal, left, and right regions of the implanted area. These polarities persisted until nine months after implantation. Hence, the results suggest that planar polarities formed in epithelia regenerated on tracheal grafts are directed toward the nearby edges of implanted areas and are preserved for a prolonged period. The polarities can, at least partially, contribute to clearing external materials from the implanted areas by transporting them to a normal region., (© 2021 John Wiley & Sons Ltd.)

Secretory carcinoma or mammary analog secretory carcinoma is an entity of salivary gland carcinoma that is characterized by the ETV6-NTRK3 gene fusion. Although it is generally considered to be a low-grade malignancy, some cases of secretory carcinoma with high-grade transformation (SCHG) have been reported. We herein describe a case of SCHG composed almost exclusively of the high-grade component. The patient presented with a growing mass in the buccal mucosa and underwent surgery. Tumor cells showing high-grade nuclear atypia were arranged in solid or cribriform nests with comedo-like necrosis. A differential diagnosis included high-grade salivary gland carcinoma, such as salivary duct carcinoma. Immunohistochemically, tumor cells were focally positive for S-100 and negative for mammaglobin and showed nuclear positivity for pan-Trk. A reverse transcription polymerase chain reaction assay showed that the tumor harbored the ETV6-NTRK3 gene fusion. A histological review of microscopic slides of the tumor did not reveal a typical secretory carcinoma component, except for a very focal area. We ultimately diagnosed this tumor as SCHG. This case underscores the importance of recognizing the histological spectrum of SCHG and the utility of pan-Trk immunohistochemistry to detect secretory carcinoma, which may be targeted by tyrosine kinase inhibitors., (© 2021 Japanese Society of Pathology and John Wiley & Sons Australia, Ltd.)

Head and neck cancers, especially in hypopharynx and oropharynx, are often detected at advanced stage with poor prognosis. Narrow band imaging enables detection of superficial cancers and transoral surgery is performed with curative intent. However, pathological evaluation and real-world safety and clinical outcomes have not been clearly understood. The aim of this nationwide multicenter study was to investigate the safety and efficacy of transoral surgery for superficial head and neck cancer. We collected the patients with superficial head and neck squamous cell carcinoma who were treated by transoral surgery from 27 hospitals in Japan. Central pathology review was undertaken on all of the resected specimens. The primary objective was effectiveness of transoral surgery, and the secondary objective was safety including incidence and severity of adverse events. Among the 568 patients, a total of 662 lesions were primarily treated by 575 sessions of transoral surgery. The median tumor diameter was 12 mm (range 1-75) endoscopically. Among the lesions, 57.4% were diagnosed as squamous cell carcinoma in situ. The median procedure time was 48 minutes (range 2-357). Adverse events occurred in 12.7%. Life-threatening complications occurred in 0.5%, but there were no treatment-related deaths. During a median follow-up period of 46.1 months (range 1-113), the 3-year overall survival rate, relapse-free survival rate, cause-specific survival rate, and larynx-preservation survival rate were 88.1%, 84.4%, 99.6%, and 87.5%, respectively. Transoral surgery for superficial head and neck cancer offers effective minimally invasive treatment. Clinical trials registry number: UMIN000008276., (© 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Objective: Involvement in the tracheostomy procedure for COVID-19 patients can lead to a feeling of fear in medical staff. To address concerns over infection, we gathered and analyzed experiences with tracheostomy in the COVID-19 patient population from all over Japan., Methods: The data for health-care workers involved in tracheostomies for COVID-19-infected patients were gathered from academic medical centers or their affiliated hospitals from all over Japan., Results: Tracheostomies have been performed in 35 COVID-19 patients with a total of 91 surgeons, 49 anesthesiologists, and 49 surgical staff members involved. Twenty-eight (80%) patients underwent surgery more than 22 days after the development of COVID-19-related symptoms (11: 22-28 days and 17: ≥29 days). Thirty (85.7%) patients underwent surgery ≥ 15 days after intubation (14: 15-21 days, 6: 22-28 days, and 10: ≥29 days). Among the total of 189 health-care workers involved in the tracheostomy procedures, 25 used a powered air-purifying respirator (PAPR) and 164 used a N95 mask and eye protection. As a result, no transmission to staff occurred during the 2 weeks of follow-up after surgery., Conclusion: No one involved in tracheostomy procedures were found to have been infected with COVID-19 in this Japanese study. The reason is thought to be that the timing of the surgery was quite late after the infections, and the surgery was performed using appropriate PPE and surgical procedure. The indications for and timing of tracheostomy for severe COVID-19 patients should be decided through multidisciplinary discussion., Competing Interests: Declaration of Competing Interest We declare that we have no conflicts of interest., (Copyright © 2021. Published by Elsevier B.V.)

Objectives: The aim of this multicenter retrospective cohort study was to compare efficacy and subsequent postoperative treatment between transoral robotic surgery (TORS) and any non-robotic transoral surgery in Japanese patients with early oropharyngeal squamous cell carcinoma (OPSCC), hypopharyngeal SCC (HPSCC), or supraglottic SCC (SGSCC)., Materials and Methods: Clinical information and surgical outcomes were compared between patients with early-stage OPSCC, HPSCC, and SGSCC who underwent TORS (TORS cohort) and those who underwent non-robotic transoral surgery, including transoral videolaryngoscopic surgery (TOVS), endoscopic laryngopharyngeal surgery (ELPS), and transoral laser microsurgery (TLM) (non-robotic cohort). The data of the Head and Neck Cancer Registry of Japan (registry cohort) were used to validate the comparison. The main outcomes were the presence of positive margins under pathology and the requirement for postoperative therapy, including radiotherapy or chemoradiotherapy., Results: Sixty-eight patients in the TORS cohort, 236 patients in the non-robotic cohort, and 1,228 patients in the registry cohort were eligible for this study. Patients in the TORS cohort were more likely to have oropharyngeal tumor disease and T2/3 disease than those in the other cohorts (P<0.001 and P=0.052, respectively). The TORS cohort had significantly fewer patients with positive surgical margins than the non-robotic cohort (P=0.018), as well as fewer patients who underwent postoperative treatment, although the difference was not significant (P=0.069). In the subgroup analysis of patients with OPSCC, a total of 57 patients in the TORS cohort, 73 in the non-robotic cohort, and 171 in the registry cohort were eligible for the present study. Patients with OPSCC who underwent TORS were more likely to have lateral wall lesions than those in the other cohorts (P=0.003). The TORS cohort also had significantly fewer patients with positive surgical margins than the non-robotic cohort (P=0.026), and no patients in the TORS cohort underwent any postoperative treatment for OPSCC, although the difference was not significant (P=0.177)., Conclusions: Our results suggest that TORS leads to fewer positive surgical margins than non-robotic transoral surgeries. The clinical significance of TORS may be further validated through the results of all-case surveillance for patients who underwent TORS running in Japan in the future., (Copyright © 2021. Published by Elsevier B.V.)

Many patients with allergic rhinitis have accompanying laryngeal symptoms such as persistent cough and/or globus. Chronic laryngeal allergy is suspected to be an important cause of these laryngeal symptoms. We have been working toward establishing the concept of a new pathological condition termed "laryngeal allergy" since 1988. In Japan, the first diagnostic criteria for laryngeal allergy were established in 1995. However, these early criteria were inadequate because there was inadequate distinction between laryngeal allergy and other causes of persistent cough and globus. Therefore, more advanced criteria were reconstructed from a completely different viewpoint in 2005 to correctly distinguish laryngeal allergy from other similar diseases. The criteria established in 2005 were modified slightly in 2011 to improve the diagnostic accuracy based on the results of fundamental and clinical investigations. The Japanese Respiratory Society (JRS) included chronic laryngeal allergy in the diagnostic flowchart of the JRS guidelines for the management of cough and sputum in 2019, and chronic laryngeal allergy has recently gained wider recognition in Japan. The accurate diagnosis of conditions resembling laryngeal allergy is important in controlling cough and/or globus and preventing the unnecessary use of medical resources. Therefore, further investigations are warranted to better understand laryngeal allergy and similar diseases., Competing Interests: The authors declare that they have no conflict of interest.

Spasmodic dysphonia (SD) is characterized by an involuntary laryngeal muscle spasm during vocalization. Previous studies measured brain activation during voice production and suggested that SD arises from abnormal sensorimotor integration involving the sensorimotor cortex. However, it remains unclear whether this abnormal sensorimotor activation merely reflects neural activation produced by abnormal vocalization. To identify the specific neural correlates of SD, we used a sound discrimination task without overt vocalization to compare neural activation between 11 patients with SD and healthy participants. Participants underwent functional MRI during a two-alternative judgment task for auditory stimuli, which could be modal or falsetto voice. Since vocalization in falsetto is intact in SD, we predicted that neural activation during speech perception would differ between the two groups only for modal voice and not for falsetto voice. Group-by-stimulus interaction was observed in the left sensorimotor cortex and thalamus, suggesting that voice perception activates different neural systems between the two groups. Moreover, the sensorimotor signals positively correlated with disease severity of SD, and classified the two groups with 73% accuracy in linear discriminant analysis. Thus, the sensorimotor cortex and thalamus play a central role in SD pathophysiology and sensorimotor signals can be a new biomarker for SD diagnosis.

Objectives/hypothesis: To regenerate defected recurrent laryngeal nerves (RLNs), various methods have been developed. However, no consistently effective treatments are currently available because of their insufficient functional recovery. RADA16-I, a self-assembling peptide used clinically as a hemostat, reportedly supports neurite outgrowth and functional synapse formation in vitro. The purpose of this study was to investigate the effect of RADA16-I hydrogels on transected RLNs in rats., Study Design: Animal experiments with controls., Methods: Fifteen adult rats were divided into the following three groups: RADA16-I (+), RADA16-I (-), and neurectomy. A 6-mm gap of the left RLN was bridged using an 8-mm silicone tube in the RADA16-I (-) and RADA16-I (+) groups. Subsequently, RADA16-I hydrogel was injected into the tube in the RADA16-I (+) group. The surgical incisions were closed without any further treatment in the neurectomy group. After 8 weeks, laryngoscopy and electrophysiological and histological examinations were performed to evaluate the effect of RADA16-I on nerve regeneration and thyroarytenoid muscle atrophy., Results: Although most rats in the three groups exhibited no improvements of their vocal fold movement, partial recovery was observed in one rat in the RADA16-I (+) group. The neurofilament-positive areas and the number of myelinated nerves in the RADA16-I (+) group were significantly higher than in the RADA16-I (-) group. The area of the left thyroarytenoid muscle in the RADA16-I (+) group was significantly larger than that of the neurectomy group., Conclusions: Our results suggested that RADA16-I hydrogel was effective for RLN regeneration., Level of Evidence: NA Laryngoscope, 130:2420-2427, 2020., (© 2019 The American Laryngological, Rhinological and Otological Society, Inc.)

Multiciliated epithelial cells in the airway are essential for mucociliary clearance. Their function relies on coordinated, metachronal and directional ciliary beating, appropriate mucus secretion and airway surface hydration. However, current conventional methods for observing human airway ciliary movement require ciliated cells to be detached from airway tissues. Determining the directionality of cilia is difficult. We developed a novel method to stain airway epithelial cilia to observe their movement without releasing ciliated cells. Human tracheae were obtained from patients (n = 13) who underwent laryngectomies to treat malignancies or swallowing disorders. The tracheae were treated with fluorescently labeled wheat germ agglutinin, which interacts with the acidic mucopolysaccharides present on the cilia. Epithelial surfaces were observed using an epi-fluorescence microscope equipped with a water-immersion objective lens and a high-speed camera. Ciliary movement was observable at 125 fps (13/13 samples). Ciliated cells in close proximity mostly exhibited well-coordinated ciliary beats with similar directionalities. These findings indicated that wheat germ agglutinin renders ciliary beats visible, which is valuable for observing human airway ciliary movements in situ.

Objectives: Transoral approaches for laryngeal/pharyngeal malignancies have been widely accepted as minimally invasive treatment options; however, hypopharyngeal lesions treated by transoral surgery have rarely been reported due to the difficulties in visualizing the hypopharynx. Since 2010, we have treated superficial hypopharyngeal lesions with endoscopic laryngopharyngeal surgery (ELPS), and herein report the outcomes of this transoral procedure., Materials and Methods: One hundred and eighteen patients with superficial hypopharyngeal lesions were treated by ELPS from February 2010 to February 2017, and the clinical courses of the patients were reviewed., Results: Four females and 114 males (average: 65.6 y-o) were included in this study. Some patients had multiple lesions and a total of 154 superficial hypopharyngeal lesions (dysplasia: 29, Tis: 52, T1: 44, T2: 20, T3: 9) were treated with ELPS. Ten patients had only dysplasia and no carcinoma. Five patients presented with nodal metastases and 11 patients had simultaneous oropharyngeal lesions. In all cases, the hypopharynx was well visualized with sufficient working space, and no cases required a change in surgical approach. All post-operative complications were safely managed. In regard to the oncological outcomes, of the 108 patients with malignant lesions, the 3-year and 5-year overall survival (OS) rate was 93.6% and 85.5%, respectively., Conclusions: During ELPS, the hypopharynx was well visualized providing sufficient working space for the resection. The procedure was safe and feasible for superficial hypopharyngeal lesions and exhibited very good oncological outcomes. ELPS is thought to be a very effective surgical alternative for superficial hypopharyngeal lesions., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

The tracheal lumen is essential for conducting air to the lung alveoli and for voice production. However, patients with severe tracheal stenosis and malignant tumors invading the trachea often require tracheal resection. Recently, various reported tissue engineering methods for tracheal reconstruction show that regeneration of ciliated epithelium in the reconstructed areas, as well as preservation of the luminal structure is possible. However, only few studies report on the mucociliary transport function in reconstructed tracheae. We investigated mucociliary transport function within rat tracheal epithelium, reorganized after autologous adipose tissue-derived stem cell (ASC) transplantation. Rat ASCs were expanded in culture, and then seeded in a collagen sponge, which was physically supported with a polypropylene framework. The ASC-seeded collagen sponge was transplanted into the rat tracheal defect. We then examined the motility and transport function of cilia generated in the transplanted area using ciliary beat frequency (CBF) and microsphere movement analyses. Our data suggested that autologous ASC transplantation promoted ciliogenesis, consistent with previous reports. The CBF analysis revealed that motility of the cilia generated in the ASC group was comparable to that observed in the normal rat tracheal epithelium. Transport function in the ASC group was higher than that in the control group. These data suggested that autologous ASC transplantation increased ciliated cells in the reconstructed area without significantly disrupting cilia motility, thereby promoting transport function regeneration. Autologous ASC transplantation is expected to be beneficial in morphological and functional regeneration of tracheal epithelium. Anat Rec, 303:471-477, 2020. © 2019 American Association for Anatomy., (© 2019 Wiley Periodicals, Inc.)

Objective: To develop a summary of the first version of the Clinical Practice Guideline of Voice Disorders for Diagnosis, Management, and Treatment in Japan by the Clinical Practice Guideline Committee of the Japan Society of Logopedics and Phoniatrics and The Japan Laryngological Association. The 2018 recommendations, based on a review of the scientific literature, are intended to serve as clinical practice guidelines for the diagnosis, management, and treatment of voice disorders in Japan., Methods: A summary of the original version of the Clinical Practice Guideline of Voice Disorders for Diagnosis, Management, and Treatment in Japan was described. Recommendations for the diagnosis, management, and treatment of voice disorders were prepared. Twelve clinical questions (CQs) regarding the diagnosis, management, treatment, and effectiveness of therapy for voice disorders were also prepared., Results: A summary of the first version of the clinical practice guidelines for the diagnosis, management, and therapy of voice disorders was prepared and is presented. Additionally, answers to the 12 CQs on the diagnosis, management, treatment, and effectiveness of voice disorder therapy were prepared, and include evidence-based recommendations., Conclusion: These guidelines present a summary of the standard approaches for the diagnosis and treatment of voice disorders and relevant CQs that consider the medical environments in Japan. We hope that the guidelines will assist physicians in clinical settings for patients with voice disorders., (Copyright © 2019. Published by Elsevier B.V.)