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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.

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.

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

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 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.

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

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.

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

Background: Adult rhabdomyoma (ARh) is a rare benign tumor of skeletal muscle origin. ARh occurs mainly in the head and neck region. This report details the surgical excision of a large multinodular ARh in the base of the tongue that was causing severe sleep apnea. Findings: Magnetic resonance imaging revealed that the base of the tongue was almost completely replaced by a 6 cm × 8 cm tumor. Methods: Conservative surgical excision was done by submental midline approach with hyoid bone split. Results: Surgery improved the patient’s sleep apnea without damaging the swallowing function. The patient was able to secede from nasal continuous positive airway pressure and has remained symptom-free for 12 months postoperatively. Conclusions: This newly designed approach is suitable for excision of benign tumors in the base of the tongue to obtain a patent airway without damaging the function of the tongue base.

We report a case of bilateral duplication of the internal auditory canal (IAC). An 11-month-old girl with congenital profound hearing loss was referred to our hospital. Imaging evaluations revealed bilateral IAC duplication, which contained the facial and cochleovestibular nerves in one canal, but no nerves in the other. She underwent cochlear implantation. At 5 months after surgery her hearing thresholds with the cochlear implant are 40 and 45 dB at 2000 and 4000 Hz, respectively. Bilateral duplicated IAC is extremely rare, with seven cases reported in the literature. This case represents a previously unreported type of IAC duplication, and is the first case in which cochlear implantation was successfully performed.

In the first section of this chapter, nasal embryology is described. An understanding of nasal embryology and anatomy is of considerable importance for regenerative medicine of the nose. Most of the components of the nasal and paranasal sinuses arise from the ectodermal germ layer. During the fifth embryonic week, nasal development starts from a small pit, which subsequently deepens to form a cavity. Formation of the soft and hard palate, and fusion of the nasal septum and the palate are completed in the twelfth embryonic week. Differentiation of the nasal respiratory epithelium is almost finished by the twenty-fourth embryonic week. In the second section of this chapter, progress in tissue engineering techniques for nasal reconstruction is summarized. Tissue engineering of the mucosa, cartilage, bone, and skin is essential for complete nasal reconstruction. The final section describes the use of regenerative medicine in restoring olfactory function. The olfactory system has a high intrinsic regenerative capacity; however, many patients experience olfactory disorders. Recent advances in the field of olfactory regenerative medicine are explained.

Microcysts of the parathyroid gland are a common occurrence in the general population, but macroscopic parathyroid cysts of the neck are rare clinical entities. We report two cases of parathyroid cyst that extended to the mediastinum. Parathyroid cysts are classified as nonfunctional and functional. We discuss the clinical features of nonfunctioning and functioning parathyroid cyst. Fine needle aspiration biopsy with ultrasonography is a very useful technique for diagnosis and treatment. In the future, we would like to attempt extirpation of mediastinal tumor from the neck by endoscopy without thoracotomy.

We report two pediatric cases of facial palsy caused by intracranial disease, and review 54 facial palsy patients under 12 years old who were admitted to Kurashiki Central Hospital between January 1991 and January 2002. Previously reported cases, congenital palsy patients and traumatic palsy patients were excluded from review.Case 1 was a 2-year-old girl, who was hospitalized due to left facial palsy. MRI revealed a well-enhanced mass both in the cerebellopontine (CP) angle and the spinal cord. The tumor in the spinal cord was pathologically diagnosed as an atypical teratoid-rhabdoid tumor, which probably caused metastasis from the CP angle to the spinal cord.Case 2 was a 5-year-old girl, who was admitted to the hospital with right facial palsy. At 3 years old, she developed right facial palsy but recovered one month later. At 4 years old, right arm and right leg palsy occurred, but recovered. MRI revealed arteriovenous malformation in the parietal lobe.Of 54 cases reviewed, 35 patients were diagnosed as having idiopathic palsy (Bell's palsy), 11 as having viral infection, 7 as having otogenic disorder, 1 as having neoplasm. We were able to follow 42 cases over a prolonged period. Of these 42 cases, 39 cases recovered, and 3 cases did not recover.Facial palsy in children is considered to have a good prognosis, but it may be the initial manifestation of a life-threatening disorder such as intracranial vascular malformation or neoplasm. When neurologic findings in addition to facial palsy are manifested or suspected, it is important to search for an intracranial lesion. MRI is a very useful method of evaluating intracranial disease.

To investigate the hypothesis that prophylactic triamcinolone modulates acute vocal fold inflammatory and profibrotic signaling during acute phonotrauma.In vivo rabbit phonation model.Academic medical center.Forty New Zealand white breeder rabbits were randomly assigned to 1 of 4 groups: control (no intervention), no treatment (30 minutes of raised intensity phonation), sham treatment (bilateral intralaryngeal triamcinolone acetonide injection at 0 µg/25 µL followed by 30 minutes of raised intensity phonation), or steroid treatment (bilateral intralaryngeal triamcinolone acetonide injection at 400 µg/25 µL followed by 30 minutes of raised intensity phonation). Quantitative polymerase chain reaction (qPCR) was used to investigate gene expression levels of cyclooxygenase-2 (COX-2), interleukin (IL)-1β, and transforming growth factor (TGF)-β1.Results revealed a significant main effect for COX-2 (P = .002). Post hoc testing revealed that rabbits receiving no treatment (15.10) had higher COX-2 gene expression than control (5.90; P.001). There were no significant differences in COX-2 expression between treatment groups. Results revealed a significant main effect for IL-1β (P.001). Post hoc testing revealed that rabbits receiving no treatment (14.70) had higher IL-1β gene expression than control (6.30) (P = .001). There were no significant differences in IL-1β gene expression between treatment groups. There were no significant differences in TGF-β1 gene expression (P = .525) between treatment and control groups.Given conflicting evidence, further studies are necessary to investigate vocal fold steroid injections prior to and following the induction of phonotrauma. Prophylactic administration of triamcinolone immediately prior to acute phonotrauma resulted in no significant changes in COX-2, IL-1β, and TGF-β1 gene transcript levels.

The purpose of this study was to investigate the feasibility of performing mucosal elevation of a vocal fold microflap in a rabbit model and to measure the acute healing of rabbit microflap incisions compared to control vocal folds.Prospective animal study.Ten New Zealand white rabbits were used in this study. All rabbits received a 3-mm incision through the epithelium of one vocal fold using a sickle knife and mucosal elevation through this incision using a microlaryngeal fine-angled spatula. The contralateral vocal fold was left intact to serve as an internal control. Student t tests were used to investigate differences in epithelial thickness, immunohistochemical staining of CD45, and inflammatory and profibrotic gene expression between vocal folds undergoing microflap and control.Exposure of the rabbit larynx was achieved, allowing for the identification of a surgical plane and the creation of a microflap and elevation of the vocal fold mucosa. Hematoxylin-and-eosin staining revealed no significant differences in epithelial thickness, immunohistochemistry for CD45 showed no significant differences in CD45-positive cells, and quantitative polymerase chain reaction revealed no significant differences in interleukin-1β, transforming growth factor β-1, or cyclooxygenase-2 gene expression between vocal folds undergoing microflap and control.We demonstrate the feasibility of vocal fold microflap surgery in a rabbit model. With the advantage of greater access to primers and antibodies for molecular biologic studies, the application of the microflap technique in a small-animal model such as rabbit has broad implications for future experimental investigations in laryngology.

Conclusions: Results of the current study revealed improved phonation threshold pressure (PTP), normalized mucosal wave amplitude (NMWA), and less contraction of the lamina propria in injured larynges treated with basic fibroblast growth factor (bFGF). Objectives: We investigated the effects of local injection of bFGF for treatment of acute vocal fold injury in a canine model. Methods: Vocal folds of eight beagles were unilaterally injured by removal of the mucosa under direct laryngoscopy. Four beagles received local injections of bFGF delivered to the scarred vocal fold at 1 month after injury. The remaining four beagles received local injections of saline and served as a sham-treatment group. Larynges were harvested 5 months after treatment and excised larynx experiments were performed to measure PTP, NMWA, and normalized glottal gap (NGG). Histologic staining was performed to evaluate structural changes of the extracellular matrix. Results: Excised larynx measurements revealed significantly lower PTP and increased NMWA in bFGF-treated vocal fold. Elastica Van Gieson staining revealed less contraction of the bFGF-treated vocal fold. Histologic measurements revealed that the thickness of the lamina propria was significantly greater in the bFGF-treated vocal fold. Alcian blue staining revealed improved restoration of hyaluronic acid in the bFGF-treated vocal fold.

Objectives We have previously demonstrated the therapeutic potential of hepatocyte growth factor (HGF) in the treatment of vocal fold scarring, although how exogenous HGF affects gene expression of endogenous HGF or extracellular matrix components in the vocal fold fibroblasts remains unclear. In this in vitro study, we aimed to clarify this aspect in order to better understand the effects of HGF on the vocal folds. Methods Fibroblasts were obtained from the lamina propria of the vocal folds of 5 Sprague-Dawley rats and were cultured with HGF at concentrations of 100, 10, 1, and 0 ng/mL. The cells were collected on days 1, 3, and 7, and the expression of endogenous HGF, its receptor c-Met, transforming growth factor-β1 (TGF-β1), procollagen types I and III, and hyaluronic acid synthase (HAS)-l and HAS-2 messenger RNAs (mRNAs) was examined by real-time reverse transcription-polymerase chain reaction. Results The expression of endogenous HGF and HAS-1 mRNAs increased significantly when exogenous HGF was administered at a concentration of 1 ng/mL. On day 1, the expression of TGF-β1 and HAS-2 mRNAs increased significantly in response to 1 ng/mL HGF. Conclusions Exogenous HGF triggered the up-regulation of endogenous HGF, TGF-β1, HAS-1, and HAS-2 mRNAs in vocal fold fibroblasts.

Objectives We examined vocal outcomes of patients who underwent type I thyroplasty for unilateral vocal fold paralysis. Specifically, the vocal outcomes were compared between 15 patients whose thyroplasties were performed with silicone and 15 patients whose thyroplasties were performed with Gore-Tex. Methods The examined clinical characteristics did not differ significantly between the groups. The vocal outcomes were evaluated by aerodynamic and acoustic measurements. Results Aerodynamic examination indicated significant postoperative improvements in the maximum phonation time and mean flow rate in both groups. Shimmer was significantly improved only in the Gore-Tex group. A direct comparison between groups showed no significant difference in the degree of improvement of the vocal parameters, except for a significant improvement in the noise-to-harmonics ratio in the Gore-Tex group. The duration of surgery was significantly less in the Gore-Tex group than in the silicone group. Conclusions Gore-Tex thyroplasty is considered to be comparable to silicone thyroplasty in terms of postoperative vocal outcomes. Gore-Tex thyroplasty enables a less invasive procedure with a shorter surgical duration and easier adjustment of medialization due to its flexibility.

Background/Objectives: Aged vocal folds are characterized by atrophy of the mucosa, which causes dysphonia and is difficult to treat. We have revealed a therapeutic potential of basic fibroblast growth factor (bFGF) for tissue regeneration of the aged vocal fold. We report here the first human case that has been treated with bFGF. Study Design: Institutional review board approved clinical human trial. Methods: A 63-year-old man with atrophied vocal folds was treated by local injection of 10 μg of bFGF into the left vocal fold under topical anesthesia. The effects of the injection were examined after 1 to 3 months by videostroboscopy, acoustic and aerodynamic measurements. Results: The atrophy of the vocal fold was improved at 1 week after the injection and glottic gap disappeared. Aerodynamic and acoustic parameters also showed remarkable improvement. These positive effects were maintained up to 3 months. Conclusion: The first case with aged vocal folds treated with bFGF administration is presented. The results are encouraging, suggesting therapeutic effects of bFGF for atrophied vocal folds in human.

Objectives: Vocal fold scarring remains a therapeutic challenge. Previous studies have indicated that hepatocyte growth factor (HGF), a strong antifibrotic element, has therapeutic potential for restoring scarred vocal folds. To enhance the effect of HGF in vivo, we developed a novel drug delivery system (DDS) in which HGF is embedded in gelatin hydrogel and continuously released over a period of 2 weeks. In the present study we investigated the therapeutic efficacy of the HGF DDS on vocal fold scarring by using a canine model. Methods: The vocal folds of 8 beagles were unilaterally scarred by stripping the entire layer of the lamina propria. The contralateral vocal folds were kept intact as normal controls. One month after the procedure, hydrogels (0.5 mL) containing 1 μg of HGF were injected into the scarred vocal folds of 4 dogs (HGF-treated group), whereas hydrogels containing saline solution were injected in the other 4 dogs (sham group). Histologic and vibratory examinations were completed for each group 6 months after the initial surgery. Results: The excised larynx experiments showed significantly better vibration in terms of mucosal wave amplitude and glottal closure in the HGF-treated group compared to the sham group. Histologic evaluation of the vocal folds indicated remarkable reduction in collagen deposition and tissue contraction, with favorable restoration of hyaluronic acid and elastin in the HGF-treated group. Conclusions: The present findings suggest that the novel HGF DDS may provide favorable effects in restoring the vibratory properties of scarred vocal folds.