Outcomes of Aspiration Prevention Surgery: A Retrospective Cohort Study Using a Japanese Claims Database.

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.

Long-term preservation of planar cell polarity in reversed tracheal epithelium.

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.

Characteristics and prognosis of patients with thyroglobulin-positive and radioactive iodine whole-body scan-negative differentiated thyroid carcinoma.

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.

Thyroid Lobectomy Under Local Anesthesia Before Lung Transplantation Owing to Diffuse Panbronchiolitis: A Case Report.

We herein report a case of thyroid lobectomy performed under local anesthesia for thyroid cancer in a patient who was at a high risk for general anesthesia due to diffuse panbronchiolitis. Although thyroid surgery has been performed in the past under local anesthesia in low-risk patients, thyroid surgery is now rarely performed under local anesthesia. If they are performed, thyroid surgery under local anesthesia is usually performed under monitored anesthesia care; sedation is considered safe and does not cause discomfort to patients. The present patient's respiratory function was poor, raising concerns that once intubated, extubation may not be possible because of the potential deterioration of respiratory function caused by the suppression of spontaneous breathing. Therefore, sedatives were avoided to maintain spontaneous breathing as much as possible. In such high-risk patients, additional care is required to ensure that the procedure is completed with minimal discomfort from pain or dyspnea. Maintaining a slightly upright position and raising the anesthesia screen are necessary to ensure a large space in front of the patient's face. In addition, an appropriate skin incision should be made to obtain a wide field of vision, and local anesthetic injections should be administered frequently to preemptively counter pain. Atropine sulfate was administered to reduce salivation and swallowing. Energy devices effectively reduced blood loss and operative time. Controlling intraoperative pain and bleeding is important, and the methods and techniques are also beneficial in surgery under general anesthesia.

Phonosurgery training using Japanese deer larynx.

OBJECTIVE: To develop phonosurgery skills, surgical training of the actual larynx is essential. In our institution, the Japanese deer (Cervus Nippon aplodontids) larynx is used in phonosurgery training. This study aimed to examine the similarities and differences between the Japanese deer and human larynx and to demonstrate their utility in vocal surgery practice. METHODS: A comparative study was conducted using 30 Japanese deer larynges and 51 human donor larynges, evaluating the overall framework, dimensions, and angle of the thyroid cartilage, vocal cord length, and location of the arytenoid cartilage muscular process. The changes and movements of the vocal folds during contraction and relaxation of each internal laryngeal muscle were also visually analyzed. RESULTS: The larynx size of Japanese deer is intermediate between that of human males and females. The adduction and abduction of the vocal folds induced by contraction of the posterior and lateral cricoarytenoid muscles, as well as the extension of the vocal folds induced by contraction of the cricothyroid muscle, behaved in the same manner as in the human larynx. CONCLUSION: The morphology of the Japanese deer larynx is similar to that of the human larynx, making it suitable for use in dissection and surgical practice. Owing to the recent animal damage problem and the popularity of gibier cuisine, large quantities of Japanese deer larynx are available at low prices. We believe that the Japanese deer larynx is the most appropriate animal for phonosurgery training so far.

Modified method for tracheoesophageal fistula closure in intractable cases.

OBJECTIVE: Tracheoesophageal puncture (TEP) is one of the most established methods for voice reacquisition following total laryngectomy. The most difficult complication following TEP is the management of saliva leakage or secretion into the trachea due to TE fistula enlargement. In this study, we devised a new strategy to close TE fistulas and confirmed its safety and effectiveness. METHODS: Skin incision: If the tracheal mucosa around the voice prosthesis appears intact and normal, an arcuate incision, from 10 to 2 o'clock, is made on the skin 5 mm superior to the edge of the stoma. However, if the surrounding tracheal mucosa is fragile because of leaking, the incision is made on the superior edge of the stoma, with later reconstruction of the posterior tracheal wall. Separation of the trachea and esophagus: If the esophagotracheal spatium appears normal and is easy to dissect, the connective pipes can be found easily. After cutting the pipe, a ligature alone is sufficient for the tracheal side; however, the esophageal wall is closed with Gambee sutures. If the esophagotracheal spatium is compromised and the posterior tracheal wall is fragile (due to saliva leakage), we remove the posterior wall and reconstruct the area using the superior skin flap. We performed our novel method on four patients with intractable conditions; postradiotherapy for laryngeal cancer, total pharyngo-laryngo-esophagectomy (TPLE) with jejunum reconstruction, TPLE with gastric lifting reconstruction, and in a patient who underwent cervicothoracic incisional drainage for descending necrotizing mediastinitis. RESULTS: None of the cases showed postoperative leakage from the fistula, and oral intake was resumed without difficulty. CONCLUSION: This study showed that this strategy based on TE fistula conditions is effective even in difficult-to-treat cases.

Osteoradionecrosis of the occipitocervical junction: A rare case of C1 anterior arch disruption.

We report the case of a 57-year-old man who developed osteoradionecrosis (ORN) at the occipitocervical (OC) junction after radiation therapy for nasopharyngeal carcinoma. During soft-tissue debridement using a nasopharyngeal endoscope, the anterior arch of the atlas (AAA) was spontaneously disrupted, which was later spat out. Radiographic examination revealed complete disruption of the AAA that caused OC instability. We performed posterior OC fixation. The patient experienced successful postoperative pain relief. AAA disruption secondary to ORN at OC junction can cause severe instability. Posterior OC fixation alone may be an effective procedure if the necrotic pharyngeal region is mild and endoscopically controllable.

Swallowing function improvement using costal cartilage for severe dysphagia after supracricoid hemilaryngopharyngectomy.

Supracricoid hemilaryngopharyngectomy (SCHLP) is a laryngeal preservation surgery for hypopharyngeal carcinoma confined to the pyriform sinus or laryngeal carcinoma with arytenoid infiltration. Postoperative dysphagia is inevitable, but both voice and swallowing functions can be preserved. Here, we present a case of severe dysphagia secondary to unexpected postoperative tissue loss and scarring. A 67-year-old man underwent left SCHLP for hypopharyngeal cancer, and on the third postoperative day, he developed necrotizing fasciitis of the left neck. He was unable to swallow and was transferred to a rehabilitation hospital 90 days after the surgery. Six months after surgery, the patient had significant glottic insufficiency due to laryngeal deformity, constant massive salivary aspiration, and difficulty releasing the cuffed cannula. Severe dysphagia due to glottic insufficiency and laryngeal elevation insufficiency due to scar formation were considered, and laryngoplasty and laryngeal suspension surgery using costal cartilage were performed on the 221st postoperative day. After the reoperation, he was able to wear a speech valve and could speak and spit out, although his glottis was still closed. On the 70th day after the reoperation, he was able to consume three meals of an oral dysphagia diet and was discharged home.

Intraoperative computed tomography imaging for laryngoplasty.

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.

Early Cochlear Implantation Allows Deaf Children to Control Voice Pitch and Loudness independently.

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Laryngeal regeneration using tissue engineering techniques in a canine model.

OBJECTIVES: We previously reported that polypropylene mesh covered with collagen sponge is a useful material for the regeneration of the trachea and the cricoid cartilage. The aim of this study was to regenerate larynges after partial hemilaryngectomy with this new biomaterial. METHODS: A left partial hemilaryngectomy was performed on 12 adult beagles. The defect size was about 1.8 x 1.0 cm. Both sides of polypropylene mesh were coated with either 1% or 3% collagen sponge. This scaffold was wrapped in fascia lata harvested from the left thigh and then fixed in place over the defect. Endoscopic examinations were performed periodically. Six months after treatment, 3-dimensional computed tomographic scanning was performed. Vibratory examinations were also performed with excised larynges. RESULTS: In the 1% collagen group, exposure or dislocation of the mesh was found in 3 of 6 cases, but in the 3% group, no exposure of the mesh was seen. The morphological findings in the vocal fold were better in the 3% group than in the 1% group, but a difference in the vertical levels of the vocal folds was found in both groups. CONCLUSIONS: This study suggests that 3% collagen-coated polypropylene mesh wrapped with autologous fascia is a useful material for laryngeal regeneration.

Axillary lymph node metastases from thyroid carcinoma: Report of seven cases.

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.

Airway ciliated cells regenerated on collagen sponge implants acquire planar polarities towards nearby edges of implanted areas.

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.

Questionnaire survey on pharyngolaryngeal sensation evaluation regarding dysphagia in Japan.

OBJECTIVE: The objective is to conduct a questionnaire survey regarding pharyngolaryngeal sensation evaluation in dysphagia to understand the current situation in Japan. METHOD: The questionnaire was sent to the councilor of the Society of Swallowing and Dysphagia of Japan and the Japanese Society of Dysphagia Rehabilitation-Certified Clinician. The prospective questionnaire survey included the questions listed below: Q1: What do you think of the importance of pharyngolaryngeal sensory evaluation? Q2: Select one of the essential swallowing sensations. Q3: Select one of the following regarding the frequency of sensory examination of the larynx. Q4: Select the proportion of cases the sensory test results affect. Q5: As a pharyngolaryngeal sensory evaluation method in swallowing function evaluation, please fill in the table below for the frequency, difficulty, and effectiveness of the following tests, such as gag reflex, touching the larynx by endoscopy, touching the larynx by the probe with endoscopy, cough reflex test, swallowing provocation test. RESULTS: The essential swallowing sensations of mechanical stimulation, chemical stimulation, thermal stimulation were 84.9%, 5.4%, and 9.7%, respectively. The frequency of touching the larynx by endoscopy in the otolaryngology group and cough reflex test in dentistry was significantly higher than the other groups (p < 0.05). The correlation between the frequency and difficulty or effectiveness of the sensory tests indicated that the frequency and difficulty are significantly correlated between each item. CONCLUSION: Our results aid in increasing understanding and selection of pharyngolaryngeal sensation evaluation for dysphagia patients.

Effects of basic fibroblast growth factor on rat vocal fold fibroblasts.

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.

A novel method for live imaging of human airway cilia using wheat germ agglutinin.

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.

A summary of the Clinical Practice Guideline for the Diagnosis and Management of Voice Disorders, 2018 in Japan.

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.

Comparative study of vocal outcomes with silicone versus Gore-Tex thyroplasty.

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.

Effect of exogenous hepatocyte growth factor on vocal fold fibroblasts.

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-beta1 (TGF-beta1), procollagen types I and III, and hyaluronic acid synthase (HAS)-1 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-beta1 and HAS-2 mRNAs increased significantly in response to 1 ng/mL HGF. CONCLUSIONS: Exogenous HGF triggered the up-regulation of endogenous HGF, TGF-beta1, HAS-1, and HAS-2 mRNAs in vocal fold fibroblasts.

Atelocollagen sponge as a stem cell implantation scaffold for the treatment of scarred vocal folds.

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 fspl 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.