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Aspiration prevention surgeries, such as laryngotracheal separation and total laryngectomy are performed to prevent aspiration pneumonia. We aimed to investigate the outcomes of surgery for intractable aspiration and relevant factors. This retrospective cohort study used a nationwide insurance claims database that included company employees and their family members aged 75 years in Japan. We extracted the data of patients who underwent aspiration prevention surgeries between January 2005 and March 2019. We identified 127 patients (males, 55.9%), of whom 59.8% were aged 18 years at the surgery. The most common comorbidity was neurological disease (99.2%). The frequency of pneumonia episodes decreased by 1.5 per year after surgery compared with before surgery (p 0.001). Among patients who received parenteral and enteral nutrition before surgery (n = 92), the adjusted hazard ratio (aHR) for oral intake without parenteral and enteral nutrition was lower in the longer preoperative duration (≥ 14.7 months) for the parenteral and enteral nutrition. However, the difference was not statistically significant (aHR 0.55; 95% confidence interval: 0.15-2.08, p = 0.38). The aHR for oral intake was higher in the ≥ 30 years group than in the 30 years group (aHR 13.76; 95% confidence intervals: 4.18-42.24; p 0.001). This study demonstrated that postoperative oral intake was achieved more frequently in patients aged ≤ 30 years than in those aged 30 years, and supported the effectiveness of aspiration prevention surgery for reducing aspiration pneumonia. Further research is necessary to investigate factors related to postoperative oral intake.

Congenitally deaf children with a cochlear implant (CI) improve their speech production intelligibility, but their prosody, including stress and intonation produced by voice pitch and loudness changes, often differs from normal hearing people, which affects their fluent oral communication. This study is aimed to clarify abnormal characteristics of voice pitch and loudness control in CI recipients using a newly developed visually guided pitch change task.We included 13 normal hearing volunteers (NH group) and 17 congenitally deaf CI users who showed good speech intelligibility. The 17 CI users were divided into Early-CI and Late-CI groups, based on their age at implantation of 2.5 years. Using the visually guided pitch change task and acoustic voice analysis of sustained vowels, we assessed their vocal skills to maintain constant pitch and loudness and intentionally change the voice pitch independent from loudness. At the time of examination, the mean age was 24.1, 12.7, and 18.9 years in the NH, Early-CI, and Late-CI groups.During constant vowel production, Early-CI and Late-CI groups showed more significant fluctuations in pitch and loudness than the NH group. However, when focusing on intentionally changing only the pitch of the voice, the Early-CI group was significantly better than the Late-CI group and comparable to the NH group in terms of their ability to change vocal pitch independently from loudness.Among congenitally deaf patients, age at implantation was associated with the development of voice skills to control voice pitch and loudness separately, which may influence their fluent prosody production.

Axillary lymph node metastasis (ALNM) of well- or poorly-differentiated thyroid cancer is rare. Notably, there are only 14 single case reports available; therefore, the mechanism of metastasis is unclear at this point. Because we encountered seven cases at a single institution, we were able to infer the mechanism of ALNM of thyroid cancer. The seven cases treated at our institution were analyzed retrospectively. In addition, 14 cases reported from other institutions were reviewed. All seven patients we treated and the 10 patients, among the 14, from other institutions were postoperative recurrences. All seven patients we treated had lymph node metastases near the venous angle, and invasive manipulation had been performed during the previous surgery. Therefore, we can presume that fibrosis at the venous angle caused by ablative surgery or tumor invasion could have resulted in anomalous lymphatic flow from the neck to the axilla. Hence, the subclavian region would probably need to be dissected besides axillary dissection. All 21 cases underwent surgical treatment for ALNM. Metastatic lymph nodes in the venous angle, subclavian or axilla, occasionally invade or adhere to the vessels. Hence, a surgical strategy is required in those cases rather than molecular targeted therapy or radioactive iodine irradiation.

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 also 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. This article is protected by copyright. All rights reserved.

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.

Tracheal epithelia have barrier and mucociliary clearance functions that prevent invasion of extraneous particles and infectious materials. Hence, following tracheal reconstructions, functional and morphological regeneration of epithelia is required to prevent respiratory declines and infectious diseases. Although growth factors (GFs) promote the regeneration of tracheal epithelial morphologies, it remains unclear whether tracheal grafts containing GFs are beneficial for regeneration of tracheal epithelial functions. Thus, we fabricated collagen sponge scaffolds containing insulin-like GF-1 (IGF-1) and the basic fibroblast, hepatocyte, and epidermal GFs (bFGFs, HGFs, and EGFs, respectively), and we evaluated the effects of the grafts on the functional regeneration of tracheal epithelia. Partial tracheal defects were imposed surgically, and collagen sponges containing IGF-1, bFGF, HGF, or EGF were then transplanted to defect sites. Subsequent immunofluorescence studies suggested that EGF and bFGF contribute to regular distributions of tight junction molecules, and tracer permeability assays suggested that EGF and bFGF promote regeneration of barrier function. Increased ciliogenesis was also observed using scanning electron microscopy in reconstructed regions treated with EGF- and bFGF-supplemented collagen sponges. However, bFGF-supplemented collagen sponges led to greater microsphere transport than did EGF-supplemented sponges. The present data suggested that collagen sponge scaffold containing bFGF promotes functional regeneration of tracheal epithelial tissues.

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.

Background Planar cell polarity (PCP) coordinates the patterning and orientation of cells and their structures along tissue planes, and although its acquisition during the formation of airway epithelium has been described, the mechanisms for its maintenance and reconstruction are poorly understood. We aimed to clarify whether ambient environment change by orthotropic autologous transplantation affected PCP at the cellular level. Methods We performed orthotropic autologous transplantation by inverting tracheal segments in rats, and then performed morphological evaluation by microscopy. The PCP of the tracheal epithelium was assessed over time by analyzing the directions of mucociliary transport and ciliary beat, the positional relationship between the basal body and basal foot, and the bias of Vang-like protein 1 (Vangl1) at 2, 4, and 6 months postoperatively. Results After 2 months, the directions of mucociliary transport and ciliary beat were preserved toward the lung in the inverted tracheal segments. The positional relationship between the basal body and the basal foot, and the bias of Vangl1, also indicated preservation of PCP in the inverted tracheal segments. Similar results were obtained at 6 months. Conclusion The PCP of ciliated epithelium was preserved in reversed trachea, even after long-term observation. Electronic supplementary material The online version of this article (10.1186/s12931-018-0726-y) contains supplementary material, which is available to authorized users.

Objectives/Hypothesis The vocal fold epithelium that includes tight junction (TJ)-based barrier function protects underlying connective tissues from external insults. TJs play an important role to control paracellular permeability of not only solutes but also ions, and preserve the vocal fold homeostasis. However, the distribution of TJs and paracellular diffusion barrier across the entire vocal fold epithelium are still unknown. The aim of this study was to identify the distribution of TJs in the vocal fold epithelium and to characterize the recovery process of TJ-based paracellular diffusion barrier in a rat model of vocal fold injury. Study Design Animal experiments with controls. Methods Normal and vocal fold–injured rats were used. Larynges were harvested for immunohistochemical examination of TJ proteins. For functional analysis, a tracer permeability assay was performed using EZ-Link Sulfo-NHS-LC-Biotin. Results TJ proteins occludin and zonula occludens 1 signals were localized to the junctional regions of the most luminal cell layers of the vocal fold epithelium. The injured region had been recovered with epithelium at 5 days postinjury, but the paracellular diffusion barrier assays revealed that biotinylation reagents diffused into the lamina propria at 5 days postinjury, and were blocked at the epithelium at 14 and 28 days postinjury. Conclusions It was strongly suggested that TJs in the vocal fold epithelium exist at the junctional regions of the first layer of stratified squamous epithelium. TJ-based paracellular diffusion barrier following vocal fold injury is recovered by 14 days postinjury, and this period corresponds with the time course of structural changes in the regenerating epithelium layer. Level of Evidence NA Laryngoscope, 2017

Intersinus septal cells (ISSC) are defined as cells confined to the thin septum separating the frontal sinuses. In 2008, Som et al. first described four cases with a mucocele proved to have arisen in ISSC. Here, we report two cases with a mucocele in ISSC, representing the second report to appear in the English literature. Case 1 involved a mucocele in the center of the frontal lesion with rudimentary bilateral frontal sinuses, which suggested that the ISSC mucocele occurred during very early development of the frontal sinuses. Case 2 concerned a mucocele in the unilocular frontal sinus invading the left orbit. The frontal sinus septum was destroyed with partial ‘Y’-shaped remnants, which implied the ballooning and bursting of the ISSC mucocele into both sides of the frontal sinus. The two different mechanisms of development of the ISSC mucoceles may vary in relation to the time of onset.

Objective Due to the rising number of elderly patients and advances in endoscopic devices, early laryngeal and pharyngeal cancers are increasingly found in elderly patients. In these cases, minimally invasive endoscopic larygo-pharyngeal surgery (ELPS) may be indicated. However, the safety and efficacy of ELPS in elderly populations has not been established. The purpose of this study was to investigate the safety, outcomes and feasibility of ELPS in very elderly patients. Methods Between February 2010 and April 2016, 29 pharyngeal cancerous or pre-cancerous lesions in 19 patients aged 75 years or older were treated with ELPS. Twenty-six resections were performed in total, and the patients’ clinical courses were reviewed. Results Sixteen patients had multiple comorbidities and moderate to severe comorbidities were observed in 17 patients. The average surgical time and hospitalization period was 54.3 min and 18.8 days, respectively. On average, oral intake began 4.4 days after the procedure, and all patients eventually received nourishment by mouth; no percutaneous endoscopic gastrostomy dependency was observed. Complications included post-operative bleeding and aspiration pneumonia in two cases each, and all complications were safely managed. The 3-year overall survival rate was 90.2% and the 3-year disease-specific survival rate was 100%. Conclusion ELPS was safely performed in elderly patients, suggesting that it is a feasible treatment option for pharyngeal lesions in very elderly patients.

Tracheal resection is often performed for malignant tumours, congenital anomalies, inflammatory lesions, and traumatic injuries. There is no consensus on the best approach for the restoration of tracheal functionality in patients with tracheal defects. Artificial grafts made of polypropylene and collagen sponge have been clinically used by our group. However, 2 months are required to achieve adequate epithelialization of the grafts in humans. This study aimed to investigate the feasibility of transplantation therapy using an artificial trachea with human-induced pluripotent stem cell (hiPSC)-derived multiciliated airway cells (hiPSC-MCACs). Collagen vitrigel membrane, a biocompatible and absorbable material, was used as a scaffold to cover the artificial trachea with hiPSC-MCACs. Analyses of hiPSC-MCACs on collagen vitrigel membrane were performed by immunocytochemistry and electron microscopy and by assessing ciliary beat frequency. Along with the artificial trachea, hiPSC-MCACs were transplanted into surgically created tracheal defects of immunodeficient rats. The survival of transplanted cells was histologically evaluated at 1 and 2 weeks after the transplantation. The hiPSC-MCACs exhibited motile cilia on collagen vitrigel membrane. The surviving hiPSC-MCACs were observed in the endotracheal epithelium of the tracheal defect at 1 and 2 weeks after transplantation. These results suggest that hiPSC-MCAC is a useful candidate for tracheal reconstruction.

Background The efficacy of posttreatment surveillance 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET)/CT was evaluated in patients with head and neck squamous cell carcinoma (HNSCC). Methods The subjects were 158 patients with HNSCC who underwent PET/CT after definitive treatment. PET/CT detection of subclinical recurrence or a second primary cancer and the effect of timing of PET/CT scans on survival were analyzed. Results Recurrence or a second primary cancer occurred in 70 patients, and 67% of these cases were detected by PET/CT. Detection rates were 17%, 9%, 5%, and 5% in the first, second, third, and fourth scans at 4, 9, 15, and 21 months, respectively. In multivariate analysis, patients who underwent early first scans had significantly better disease-specific (hazard ratio [HR] = 0.37; p = .031) and overall (HR = 0.45; p = .040) survival compared with those who underwent late first scans. Conclusion Earlier detection of subclinical lesions by surveillance PET/CT within 4 months after treatment may improve survival in patients with HNSCC. © 2015 Wiley Periodicals, Inc. Head Neck 38: E511–E518, 2016

OBJECTIVE: The prognosis of differentiated thyroid carcinoma is generally favorable. However, some patients have negative radioiodine whole-body scans and detectable serum thyroglobulin with biochemical radioiodine-refractory carcinoma and are candidates for treatment with a multikinase inhibitor, such as sorafenib. The purpose of this study is to investigate the characteristics and prognosis of differentiated thyroid carcinoma patients who are thyroglobulin positive and scan negative. METHODS: We retrospectively classified 153 patients treated for 15 years by serum thyroglobulin level and radioiodine scan results and examined the relationship between clinical characteristics and prognosis. RESULTS: Overall, 27% of the patients were classified as thyroglobulin positive/scan negative (positive/negative) while 61% were thyroglobulin negative/scan negative (double negative). Compared with double-negative patients, positive/negative patients were significantly older, predominantly male, had a higher pT and pN, stage, and had higher pre-operative thyroglobulin values. Positive/negative patients showed worse prognosis in terms of overall survival, disease-specific survival and disease-free survival than double-negative patients (10-year overall survival, 85 vs. 93%, P = 0.001; 10-year disease-specific survival, 94 vs. 100%, P = 0.03, 10-year disease-free survival, 77 vs. 93%, P < 0.001). Multivariate analysis revealed that positive/negative status was the only factor associated with disease-free survival, including age and TNM stage (hazard ratio: 6.37, 95% confidence interval: 1.22-33.3). However, the median duration of disease-free period for positive/negative patients was 14.2 years. CONCLUSIONS: Few patients among thyroglobulin-positive/scan-negative patients are candidates for sorafenib, despite the significant survival differences from double-negative patients.

The vocal fold epithelium that includes tight junction (TJ)-based barrier function protects underlying connective tissues from external insults. TJs play an important role to control paracellular permeability of not only solutes but also ions, and preserve the vocal fold homeostasis. However, the distribution of TJs and paracellular diffusion barrier across the entire vocal fold epithelium are still unknown. The aim of this study was to identify the distribution of TJs in the vocal fold epithelium and to characterize the recovery process of TJ-based paracellular diffusion barrier in a rat model of vocal fold injury.Animal experiments with controls.Normal and vocal fold-injured rats were used. Larynges were harvested for immunohistochemical examination of TJ proteins. For functional analysis, a tracer permeability assay was performed using EZ-Link Sulfo-NHS-LC-Biotin.TJ proteins occludin and zonula occludens 1 signals were localized to the junctional regions of the most luminal cell layers of the vocal fold epithelium. The injured region had been recovered with epithelium at 5 days postinjury, but the paracellular diffusion barrier assays revealed that biotinylation reagents diffused into the lamina propria at 5 days postinjury, and were blocked at the epithelium at 14 and 28 days postinjury.It was strongly suggested that TJs in the vocal fold epithelium exist at the junctional regions of the first layer of stratified squamous epithelium. TJ-based paracellular diffusion barrier following vocal fold injury is recovered by 14 days postinjury, and this period corresponds with the time course of structural changes in the regenerating epithelium layer.NA. Laryngoscope, 128:E150-E156, 2018.

The usefulness of addition of positron emission tomography/computed tomography (PET/CT) in decisions as to whether to perform neck dissection in patients with T1-T2 lingual squamous cell carcinoma (SCC) might be limited, but adding the condition of lymph nodes with a maximum standardized uptake value (SUVmax)4.5 to existing criteria would be helpful.The purpose of this study was to investigate the usefulness of PET/CT for performing neck dissection in patients with T1-T2 lingual SCC.This retrospective review surveyed 19 patients with T1-T2 lingual SCC who underwent neck dissection after meeting one or more of the following criteria: (1) clinically positive nodes; (2)4 mm thickness; (3) ≥ 3 cm longest diameter of the primary tumor. Focal 18F-fluorodeoxyglucose (FDG) uptake was considered to indicate PET-positive nodes (PET + Ns). The relation between pathologically positive nodes (p + Ns) and PET + Ns was estimated.There were 14 PET + Ns at 12 of 66 levels (18%) in 8 of the 19 (42%) patients. There were also 6 p + Ns (1%) among 412 nodes at 5 cervical lymph node levels (8%) in 5 patients (26%). The sensitivity and specificity for PET/CT were 80% and 64%, respectively. The SUVmax was measured, and receiver operating characteristic (ROC) analysis was undertaken to obtain better accuracy. The sensitivity and specificity were 60% and 100% when the SUVmax cut-off value was set at 4.5.

Extra-abdominal desmoid tumor, also known as aggressive fibromatosis, has aggressive behavior with local infiltration and tendency for recurrence. Though head and neck is reported to be one of the most common sites, a desmoid tumor in the larynx is extremely rare. A 67-year-old male visited our hospital with prolonged hoarseness and received laryngo-microsurgery with the diagnosis of laryngeal polyp. After the operation, he eventually developed a laryngeal squamous cell carcinoma with papilloma, confirmed by second laryngo-microsurgery and received radiation therapy. After the third laryngo-microsurgery to remove residual papilloma, white irregular mass appeared on the right vocal cord and grew rapidly beneath the glottis, causing dyspnea. After 2 additional laryngo-microsurgeries, he was diagnosed having the dermoid tumor co-existing with recurrent squamous cell carcinoma. He underwent near-total laryngectomy and is currently alive without disease, speaking using a vocal shunt. Only five cases of the desmoid tumors arising in the adult larynx have been reported in the English literature. In this case, repeated surgery and radiation were suspected as the causes. Also, the present report is the first to describe desmoid tumor co-existing with recurrent squamous cell carcinoma in the larynx.

Objectives/Hypothesis: Radiotherapy is one of the most effective treatments for head and neck cancer. However, in addition to the target tumor, normal salivary glands are also included in the irradiation field. This unavoidably results in dry mouth syndrome as a side effect. In this study, the protective efficacy of basic fibroblast growth factor (bFGF) was investigated in radiation-damaged salivary glands. Study Design: Prospective animal experiment with control. Methods: Nine-week-old female C57BL/6 mice were divided into three groups. All mice in two of the three groups were irradiated (10 Gy) at the same time. In the bFGF-treated group, bFGF was administered to the submandibular glands for 3 consecutive days after neck irradiation. Mice in the untreated control group were administered distilled water. Mice in the third group were not irradiated and did not receive any additional treatments. Saliva flow rate and submandibular gland morphology were assessed, and the apoptotic response of irradiated submandibular glands was also evaluated. Results: Administration of bFGF improved hyposalivation 8 weeks after irradiation, and histologic analysis revealed that bFGF-treated glands contained more acinar cells compared to untreated glands. The apoptotic response to irradiation, examined 1 and 2 days after irradiation, was reduced, and quantitative real-time polymerase chain reaction revealed a paracrine effect for bFGF in the glands that received bFGF treatment. Conclusions: Our study indicates that bFGF prevents salivary gland dysfunction after irradiation. The protective benefits of bFGF may be attributed to the inhibition of radiation-induced apoptosis as well as the paracrine effect it has in these tissues.

Objectives/Hypothesis: We investigated the hypothesis that 30 minutes of raised intensity phonation alters transcript levels of vocal fold intercellular tight junction proteins and disrupts the vocal fold epithelial barrier. Study Design: Prospective animal study. Methods: Eighteen New Zealand white breeder rabbits were randomly assigned to receive 30 minutes of raised intensity phonation or approximation of the vocal folds without phonation. Quantitative polymerase chain reaction (qPCR) was used to investigate transcript levels of the epithelial intercellular tight junction proteins, occludin and zonula occludin-1 (ZO-1), and the adherens junction proteins β-catenin and E-cadherin. Structural alterations to the vocal fold epithelium were further examined by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Results: Mann-Whitney U revealed significantly decreased occludin (P = .016) and β-catenin (P = .016) gene expression from rabbits undergoing raised intensity phonation compared with control. There were no significant differences in Z0-1 and E-cadherin gene expression between groups (P > .025). SEM revealed significant obliteration, desquamation, and evidence of microhole formation in rabbit vocal folds exposed to raised intensity phonation compared with control, whereas TEM revealed dilated intercellular morphology between groups. Conclusions: Results provide support for the hypothesis that a transient episode of raised intensity phonation alters transcript levels of vocal fold intercellular tight junction proteins and disrupts integrity of the epithelial barrier. The loss of barrier integrity may have significant consequences on epithelial defenses and compromise protection of the underlying mucosa from damage secondary to prolonged vibration exposure.

Objectives: Treatment of vocal fold scarring remains a therapeutic challenge. Our group previously reported the efficacy of treating injured vocal folds by implantation of bone marrow—derived stromal cells containing mesenchymal stem cells. Appropriate scaffolding is necessary for the stem cell implant to achieve optimal results. Terudermis is an atelocollagen sponge derived from calf dermis. It has large pores that permit cellular entry and is degraded in vivo. These characteristics suggest that this material may be a good candidate for use as scaffolding for implantation of cells. The present in vitro study investigated the feasibility of using Terudermis as such a scaffold. Methods: Bone marrow—derived stromal cells were obtained from GFP (green fluorescent protein) mouse femurs. The cells were seeded into Terudermis and incubated for 5 days. Their survival, proliferation, and expression of extracellular matrix were examined. Results: Bone marrow—derived stromal cells adhered to Terudermis and underwent significant proliferation. Immunohistochemical examination demonstrated that adherent cells were positive for expression of vimentin, desmin, fibronectin, and fsp1 and negative for beta III tubulin. These findings indicate that these cells were mesodermal cells and attached to the atelocollagen fibers biologically. Conclusions: The data suggest that Terudermis may have potential as stem cell implantation scaffolding for the treatment of scarred vocal folds.

We developed a system with a simple structure for sensing movement during swallowing through simple operations using piezoelectric poly(l-lactic acid) (PLLA) braided cords as a motion sensor. In the system, the analog-signal-processing part of the PLLA braided cord sensor is composed of analog-signal-adjusting parts, a multiplexer, an analog-to-digital (A/D) converter, and so forth, the data is processed on a personal computer, and finally the dependence of the signal intensity on the position and time of the motion during swallowing is plotted as a three-dimensional plot. The results of a swallowing function test using our developed system appeared to coincide with that of a diagnostic test described in a medical textbook. In addition, the subject experienced little restriction of the motion during the measurement using our system. The experimental results suggest that our system has potential use as a wearable device as a useful and portable tool for healthcare.

Objectives The overarching goal of this line of research is to translate basic fibroblast growth factor (bFGF) treatment for vocal fold scarring into practical clinical use. In a previous canine investigation, we demonstrated that bFGF improves phonation threshold pressure, mucosal wave amplitude, and histologic measures in vocal folds treated after injury. In the present study, we studied the effects of bFGF on gene expression of the extracellular matrix and growth factors in rat vocal fold fibroblasts. Methods Fibroblasts harvested from the vocal folds of 5 rats were treated with 3 concentrations of bFGF (0, 10, and 100 ng/mL). The fibroblasts were collected at 24 hours and 72 hours after bFGF administration. Quantitative polymerase chain reaction was then used to investigate the gene expression of the investigated growth factors and extracellular matrices. Results The results revealed significantly down-regulated expression of procollagen I and significantly up-regulated expression of hyaluronic acid synthase (HAS) 2 and fibronectin in fibroblasts treated with bFGF. The administration of bFGF also resulted in the up-regulation of bFGF and hepatocyte growth factor (HGF). No changes in the expression of HAS-1, tropoelastin, or procollagen III were observed between the treatment and control conditions. Conclusions Treatment with bFGF induces the down-regulation of procollagen I and the up-regulation of HAS-2 in vocal fold fibroblast cell cultures. These gene expression alterations to key mediators of the wound healing process may translate into potential benefits in the remediation of vocal fold injury. The up-regulation of HGF, an antifibrotic effector molecule, may demonstrate additional benefits by optimizing the wound healing environment and by accelerating the wound repair cascade. These findings may provide fuel for additional discoveries into the development of growth factor therapy for the treatment of vocal fold scar.

This new regenerative therapy shows great potential for the treatment of stenosis of the trachea and/or cricoids (STC).To estimate the potential of tissue-engineered artificial trachea (AT) for treatment of STC in clinical applications. We previously reported that AT was a useful material for implantation into a tracheal defect after resection of cancer. There are many causes of stenosis of the respiratory tract and STC is particularly difficult to treat.The AT was a spiral stent composed of Marlex mesh made of polypropylene and covered with collagen sponge made from porcine skin. Three patients with STC were treated by this tissue-engineering method. All of them suffered from STC caused by long endotracheal intubations. They underwent a two-stage operation. In the first operation, after resection of the stenotic regions, the edge of the tracheal cartilage was sutured to the edge of the skin. The tracheal lumen was exposed and a T-shaped cannula was inserted into the large tracheostoma. At 3 weeks to 2 months after the first operation, the trachea and skin were separated. The trimmed AT with venous blood and basic fibroblast growth factor (b-FGF) was then implanted into the cartilage defect.Postoperatively, all patients were able to breathe easily and had no discomfort in their daily activities. Six months after the second operation, we observed enough air space in the trachea and cricoid by computed tomography (CT) imaging and fiber endoscopy.

Medialization thyroplasty was effective in improving swallowing function as well as vocal function in most cases with unilateral vocal fold paralysis. The impact of medialization thryoplasty was insufficient for the case with severe atrophy and that in which the vocal fold was fixed in the lateral position.To evaluate the impacts and limitations of medialization thyroplasty on swallowing function of the patients with unilateral vocal fold paralysis.Eight cases (mean age 68.5 years) with unilateral vocal fold paralysis chiefly complaining of swallowing disturbance were studied. All patients underwent thyroplasty type I. The causes of the paralysis were lung cancer in four cases, esophageal cancer in one case, aortic aneurysm in one case, subarachnoid hemorrhage in one case, and unknown in one case. Subjective swallowing function score, maximum phonation time (MPT), mean flow rate (MFR), amplitude perturbation quotient (APQ), and pitch perturbation quotient (PPQ) were examined pre- and postoperatively.The swallowing score improved in all except two cases. However, bilateral thryoplasty was necessary for the case with severe vocal fold atrophy and arytenoid adduction was needed for the case in which the vocal fold was fixed in the lateral position. The swallowing score, MPT, and MFR showed significant improvement after surgery.

Objectives/Hypothesis: Therapeutic challenges exist in the management of vocal fold scarring. We have previously demonstrated the therapeutic potential of hepatocyte growth factor (HGF) in the management of acute phase vocal fold scarring using a novel hydrogel-based HGF drug delivery system (DDS). However, the effect of HGF on matured vocal fold scarring remains unclear. The current study aims to investigate the effect of HGF-DDS on chronic vocal fold scarring using a canine model. Study Design: Animal model. Methods: Vocal folds from eight beagles were unilaterally scarred by stripping the entire layer of the lamina propria; contralateral vocal folds were kept intact as normal controls. Six months after the procedures, hydrogels (0.5 mL) containing 1 μg of HGF were injected into the scarred vocal folds of four dogs (HGF-treated group). Hydrogels containing saline solution were injected into the other four dogs (sham group). Histological and vibratory examinations on excised larynges were completed for each group 9 months after the initial surgery. Results: Experiments conducted on excised larynges demonstrated significantly better vibrations in the HGF-treated group in terms of mucosal wave amplitude. Although phonation threshold pressure was significantly lower in the HGF-treated group compared with the sham group, no significant differences were observed in the normalized glottal gap between HGF-treated and sham groups. Histological examinations of the HGF-treated vocal folds showed reduced collagen deposition and less tissue contraction with favorable restoration of hyaluronic acid. Conclusions: Results suggest that administration of HGF may have therapeutic potential in the treatment of chronic vocal fold scarring. Laryngoscope, 2010

Calcium alginate (CA) membrane prevents excessive fibrous tissue intrusion and/or dislocation of a bone scaffold. However, CA membrane did not always accelerate cranial bone regeneration.We previously reported skull regeneration using a bone substitute material (BSM), which consisted of collagen-coated beta-tricalcium phosphate and autologous bone fragments, and bone marrow-derived stromal cells (BSCs). However, excessive fibrous tissue intrusion or dislocation of the BSM occasionally interrupted bone regeneration. To avoid such problems, we examined CA membrane, which is useful for guided bone regeneration (GBR), to investigate whether this material maintains the bone regenerative space.Bone defects (2x2 cm) were created in the skulls of 12 adult beagle dogs using the same clinical procedure. Four experimental models were tested with or without BSM plus BSCs or CA membrane. In group I, the original free bone flap was replaced at the defect. In group II, after replacing the bone flap, the defect was covered with CA membrane. In group III, BSM plus BSCs were used as a gap filler. In group IV, BSM plus BSCs and CA membrane were applied. Histological examinations were performed 3 and 6 months after the operation.In groups I and II, bone regeneration was not observed but fibrous tissue intrusion was prevented in group II. Bone neogenesis was more observed in group III than in group IV at 3 months (p0.05). At 6 months, the regenerated areas were larger than those observed at 3 months, but the differences between groups III and IV were not statistically significant.

Objectives: Venous malformations are benign lesions with thin, fragile mucosa overlying a vascular stroma. Vascular anomalies often manifest as subglottic lesions in infants, but venous malformations in adults are rare in the pharyngolaryngeal region. The treatments include open and endoscopic surgery; intraoperative bleeding is often troublesome. Angiolytic lasers such as the potassium titanyl phosphate (KTP) laser enable photocoagulation for such hemorrhagic lesions without bleeding; we report findings from a series of adult patients. Methods: Seven adults were treated with a KTP laser set at a low power of 1.5 W in continuous mode. Photocoagulation was easily performed for shallow lesions; however, laser irradiation of bulky venous malformations resulted only in surface photocoagulation. In such cases, the crust remaining after photocoagulation was removed, and laser energy was repeatedly delivered until no remnant lesion was seen. An office procedure using flexible endoscopy was performed under topical anesthesia for 1 patient with a limited lesion. Results: The lesions were well controlled in all cases without major complications. A patient with a large obstructing lesion had a relapse. Because the recurrent lesion is small and the patient does not desire additional treatment at this time, she is being observed carefully. Conclusions: Photocoagulation using the KTP laser is a feasible and relatively safe treatment for pharyngolaryngeal venous malformations in adults.

Vocal fold scarring remains a therapeutic challenge. Our research group has indicated that bone marrow-derived stromal cells (BSCs) may have therapeutic potential in restoration of injured vocal folds. However, it is still unclear how BSCs restore the viscoelasticity of vocal fold mucosa. Since a feature of vocal fold scarring is the disorganization of the extracellular matrix (ECM), it is important to understand how BSCs produce ECM. The present study aimed to clarify ECM gene expression in BSCs, and also examined the effects of hepatocyte growth factor (HGF) on this expression. BSCs obtained from the femurs of four Sprague−Dawley rats were cultured with or without HGF. The mRNA expression of ECM components (type I procollagen, decorin, Has2, CD44, MMP-1, and GAPDH) were examined in cultured BSCs and the vocal fold mucosa by the reverse transcription-polymerase chain reaction (RT-PCR). The mRNA expression of Has2 and MMP-1 was significantly stronger in BSCs than in the vocal folds (P < 0.05). Expression of Has2 in BSCs was significantly increased by the administration of HGF (P < 0.05). There was no significant difference in the gene expression of other ECM molecules between BSCs and vocal fold mucosa. Increased expression of Has2 and MMP-1 genes from BSCs may have a positive potential in the treatment of vocal fold scarring.

Objectives: The regenerative processes of the vocal fold, or the existence of stem cells in the folds, are unknown. Side population (SP) cells are defined as cells that have the ability to exclude the DNA binding dye, Hoechst 33342. They are regarded as a cell population enriched with stem cells and can be isolated from non-SP cells by a fluorescence-activated cell sorter. This study was designed to determine whether SP cells exist in the human vocal fold, as a first step in elucidating the regenerative mechanisms of the vocal fold. Methods: Seven human excised larynges were used in this study. Two were used for fluorescence-activated cell sorter analysis, and 5 were subjected to immunohistochemical analysis with antibodies against an adenosine triphosphate binding cassette transporter family member, ABCG2, which is expressed in SP cells. Results: The number of SP cells in the human vocal fold was about 0.2% of the total number of cells. ABCG2-positive cells were identified in both the epithelium and subepithelial tissue throughout the entire vocal fold. Conclusions: This preliminary study demonstrated the existence of SP cells in the human vocal fold. Further studies are warranted to clarify how these cells work in the vocal fold, particularly in the regenerative process.

Masaru Yamashita1,2), Shin-ichi Kanemaru1,*), Shigeru Hirano1), Yoshihiro Tamura1), Hiroo Umeda1), Tsunehisa Ohno1), Atsushi Suehiro1), Koichi Omori3), Tatsuo Nakamura4), and Juichi Ito1) 1)Department of Otolaryngology Head and Neck Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan 2)Division of Otolaryngology Head and Neck Surgery, Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI, U.S.A. 3)Department of Otolaryngology, Fukushima Medical University, Fukushima, Japan 4)Department of Bioartificial Organs, Institute for Frontier Medical Sciences, Kyoto University, Kyoto, Japan