楯谷 一郎

Background Although tracheal invasion from thyroid cancer is life-threatening, the epidemiology of its development remains unclear. This study aimed to determine the epidemiology (prevalence, incidence, and risk factors) and functional outcomes of tracheal invasion from thyroid cancer among Japanese patients who were eligible for full-layer tracheal resection. Methods Patients with thyroid cancer and with or without tracheal invasion were identified based on procedure codes using a large inpatient database that is maintained by a data vendor. The prevalence and incidence were estimated for each age and sex using Japanese volume of thyroidectomies and Japanese population data. We also explored whether a tumor-related tracheal defect was successfully reconstructed after full-layer tracheal resection. Results Among the 8482 patients with thyroid cancer, the overall prevalence of tracheal invasion was 0.4–0.7%. The overall incidence of thyroid cancer was 12.0/100,000 persons, and the incidence of tracheal invasion was estimated to be 0.05–0.09/100,000 persons. The age distributions were noticeably different between thyroid cancer cases with and without tracheal invasion. The highest incidence was observed at ages of 70–79 years for thyroid cancer with tracheal invasion and 60–69 years for thyroid cancer without invasion. Approximately one-half of patients experienced long-term use of a tracheal tube and/or multiple operations for tracheal reconstruction. Conclusion The peak incidence of tracheal invasion from thyroid cancer was observed at ages of >70 years. In addition, conventional surgical management appears to be limited in its ability to reconstruct tracheal defects.

Objectives Professional voice users, such as singers and teachers, are at greater risk of developing vocal fold injury from excessive use of voice; thus, protection of the vocal fold is essential. One of the most important factors that aggravates injury is the production of reactive oxygen species at the wound site. The purpose of the current study was to assess the effect of astaxanthin, a strong antioxidant, on the protection of the vocal fold from injury and inflammation due to vocal loading. Study Design This study is an institutional review board-approved human clinical trial. Methods Ten male subjects underwent a 60-minute vocal loading session and received vocal assessments prior to, immediately after, and 30 minutes postvocal loading (AST(−) status). All subjects were then prescribed 24 mg/day of astaxanthin for 28 days, after which they received the same vocal task and assessments (AST(+) status). Phonatory parameters were compared between both groups. Results Aerodynamic assessment, acoustic analysis, and GRBAS scale (grade, roughness, breathiness, asthenia, and strain) were significantly worse in the AST(−) status immediately after vocal loading, but improved by 30 minutes after loading. In contrast, none of the phonatory parameters in the AST(+) status were statistically worse, even when measured immediately after vocal loading. No allergic responses or adverse effects were observed after administration of astaxanthin. Conclusions The current results suggest that astaxanthin can protect the vocal fold from injury and inflammation caused by vocal loading possibly through the regulation of oxidative stress.

Background: There are currently no effective therapeutic methods for locally recurrent, metastatic, or progressive radioactive iodine (RAI)-refractory differentiated thyroid cancer. However, multitargeted tyrosine kinase inhibitors (TKIs) such as lenvatinib or sorafenib have been approved for patients with RAI-refractory differentiated thyroid cancer as a second targeted therapy, and these agents can prolong patient survival. However, several cases have been reported that TKIs have caused fatal complications such as fistula formation or bleeding. Case presentation: We report a case of a 53-year-old woman, who underwent repeated neck dissections and RAI therapy after total thyroidectomy in an outside hospital. Pathology revealed a papillary carcinoma of the tall cell variant. Locoregional recurrence was not under control; therefore, she visited our hospital. Although surgery was performed for locoregional recurrences three times in our hospital, they were not under control and distant metastases were found in the lung and bone a year later. Therefore, although sorafenib was initiated, the locoregional recurrence progressed 6months later and computed tomography (CT) showed a 7-cm mass in the right subclavicular lesion. Lenvatinib was started at a dose of 24mg daily. However, although tumor was rapidly reduced, an ulcer occurred in the right subclavicular lesion and was gradually increasing in size. The pulsation of subclavicular artery was found in the deep portion of the ulcer. Therefore, a pectoralis major myocutaneous flap was transplanted to cover the ulcer. Lenvatinib was an antiangiogetic TKI; therefore, it was preoperatively discontinued for 8days and postoperatively for 12days. The postoperative course was uneventful. Conclusions: Fistula formation or bleeding is known to be a severe side effect of antiangiogenic TKIs such as lenvatinib or sorafenib. There is a possibility that severe complications can occur when initiating TKIs in patients whose tumor has invaded into the skin, vessels, trachea, esophagus, and other areas. Therefore, it is necessary to use antiangiogenic TKIs very carefully. It is important to determine the appropriate time to start TKIs; however, there is no established protocol for this, and it is a problem that needs urgent attention.

Objectives. Superficial-type pharyngeal squamous cell carcinoma (STPSCC) is defined as carcinoma in situ or microinvasive squamous cell carcinoma without invasion to the muscular layer. An exploration of the biological characteristics of STPSCC could uncover the invasion mechanism of this carcinoma. Phosphatidylcholine (PC) in combination with fatty acids is considered to play an important role in cell motility. Imaging mass spectrometry (IMS) is especially suitable for phospholipid analysis because this technique can distinguish even fatty acid compositions. Study Design. IMS analysis of frozen human specimens. Methods. IMS analysis was conducted to elucidate the distribution of PC species in STPSCC tissues. STPSCC tissue sections from five patients were analyzed, and we identified the signals that showed significant increases in the subepithelial invasive region relative to the superficial region. Results. Three kinds of PC species containing arachidonic acid, that is, PC (16:0/20:4), PC (18:1/20:4), and PC (18:0/20:4), were increased in the subepithelial invasive region. Conclusion. These results may be associated with the invasion mechanism of hypopharyngeal carcinoma.

Objectives Voice rest is commonly recommended after phonomicrosurgery to prevent worsening of vocal fold injuries. However, the most effective duration of voice rest is unknown. Recently, early vocal stimulation was recommended as a means to improve wound healing. The purpose of this study is to examine the optimal duration of voice rest after phonomicrosurgery. Study Design Randomized controlled clinical study. Methods Patients undergoing phonomicrosurgery for leukoplakia, carcinoma in situ, vocal fold polyp, Reinke's edema, and cyst were chosen. Participants were randomly assigned to voice rest for 3 or 7 postoperative days. Voice therapy was administered to both groups after voice rest. Grade, roughness, breathiness, asthenia, and strain (GRBAS) scale, stroboscopic examination, aerodynamic assessment, acoustic analysis, and Voice Handicap Index-10 (VHI-10) were performed pre- and postoperatively at 1, 3, and 6 months. Stroboscopic examination evaluated normalized mucosal wave amplitude (NMWA). Parameters were compared between both groups. Results Thirty-one patients were analyzed (3-day group, n = 16; 7-day group, n = 15). Jitter, shimmer, and VHI-10 were significantly better in the 3-day group at 1 month post operation. GRBAS was significantly better in the 3-day group at 1 and 3 months post operation, and NMWA was significantly better in the 3-day group at 1, 3, and 6 months post operation compared to the 7-day group. Conclusions The data suggest that 3 days of voice rest followed by voice therapy may lead to better wound healing of the vocal fold compared to 7 days of voice rest. Appropriate mechanical stimulation during early stages of vocal fold wound healing may lead to favorable functional recovery.

Objectives/Hypothesis Vocal fold scar remains a therapeutic challenge. Mesenchymal stromal cells (MSCs) are promising tools for regenerative medicine. Nevertheless, few in vivo studies have directly compared various sources of MSCs. The aim of this study was to investigate the therapeutic potential of adipose-derived stromal cells (ASCs) in comparison with bone marrow-derived stromal cells (BMSCs) for vocal fold regeneration. Study Design Prospective animal experiments with controls. Methods Two months after stripping of the lamina propria, 18 beagles were divided into four implantation groups: atelocollagen alone (collagen group), atelocollagen with BMSCs (BMSC-collagen), atelocollagen with ASCs (ASC-collagen), or a sham-treated group. One or 6 months after implantation, vibratory and histological examinations were performed. Results Mucosal vibration was significantly improved in both of the MSC-implanted groups compared with the sham-treated group, whereas only the ASC-collagen group showed a significantly smaller glottal gap than the collagen group. Moreover, in the ASC-collagen group, a significant reduction of collagen density was observed compared to the sham-treated group, and there was a trend for better restoration of hyaluronic acid (HA). Implanted MSCs were detected 1 month postimplantation; however, none survived 6 months postimplantation. Conclusions Although implantation of an atelocollagen sponge and ASCs into vocal fold scars induced vibratory recovery comparable to that of BMSCs, ASCs might have more potential in terms of restoration of HA and suppression of excessive collagen deposition.

In the management of laryngeal pre-cancerous lesions such as dysplasia or carcinoma in situ (CIS), it is important that lesion regression occur without any complications. As a minimally invasive treatment option, photocoagulation therapy using angiolytic lasers has been attracting attention. Therapeutic effects have been reported for this type of treatment, however, vocal function after treatment has not been well discussed. In this retrospective case series, we examined the therapeutic effects of photocoagulation therapy on laryngeal dysplasia and the impact on vocal function. Twenty-four patients with laryngeal dysplasia or CIS were treated with photocoagulation therapy using angiolytic lasers. Two patients were treated under general anesthesia, the remaining 22 patients were treated with topical anesthesia. Before and after treatment the extent of the lesion and vocal function was evaluated by endoscopic examination and acoustic and aerodynamic analyses, respectively. More than 50 % disease regression was observed in 20 of 24 patients. Acoustic and aerodynamic analyses revealed improvement in pitch perturbation quotient with no impairment in other parameters. Photocoagulation therapy using angiolytic lasers has proven to be feasible and safe for the treatment of laryngeal dysplasia.

Objectives/Hypothesis Stem cells are known to proliferate at a slow rate in adult organs, and thus slow-cycling cells exhibiting pluripotency are considered tissue-specific stem cells in some organs. Slow-cycling cells in the vocal fold (VF) have not been well documented. Here we sought to clarify the distributions and characteristics of slow-cycling cells in rat VFs. Methods We applied double-labeling technique to detect the distribution of slow-cycling cells. We injected the exogenous proliferation marker 5-bromo-2'-deoxyuridine (BrdU) into Sprague-Dawley rats. After a chasing period, VFs were immunostained with antibodies to BrdU and the second endogenous proliferation marker, Ki-67. BrdU (+) Ki-67(+) cells were regarded as slow-cycling cells and counted by VF regions. To reveal slow-cycling cells' characteristic, their immunophenotypes were histologically investigated and their kinetics in injured VFs were evaluated. Results Most slow-cycling cells were detected in the basal layer of the epithelium. Slow-cycling cells in the epithelium displayed a low positive ratio of E-cadherin and CK5 and a high positive ratio of vimentin and CD31 as compared with the other epithelial cells. The expression of S100A4 was low in slow-cycling cells of the lamina propria and the macula flava. FGFR1, HAS1, HAS2, and HAS3 were not detected in the slow-cycling cells. A time-dependent reduction of slow-cycling cells was observed in injured VFs. Conclusion Most slow-cycling cells resided in the epithelium, exhibiting various phenotypes in a relatively undifferentiated condition, and they are suspected to contribute to the tissue repair of the injured VFs.

Objectives. Vocal fold scarring is one of the most challenging laryngeal disorders to treat and there are currently no consis­tently effective treatments available. Our previous studies have shown the therapeutic potential of basic fibroblast growth factor (bFGF) for vocal fold scarring. However, the histological effects of bFGF on scarred vocal fold have not been elucidated. The aim of this study was to examine the histological effects of bFGF on chronic vocal fold scarring. Methods. Sprague-Dawley rats were divided into phosphate buffered saline (sham) and bFGF groups. Unilateral vocal fold stripping was performed and the drug was injected into the scarred vocal fold for each group 2 months postopera­tively. Injections were performed weekly for 4 weeks. Two months after the last injection, larynges were harvested and histologically analyzed. Results. A significant increase of hyaluronic acid was observed in the vocal fold of the bFGF group compared with that of the sham group. However, there was no remarkable change in collagen expression nor in vocal fold contraction. Conclusion. Significant increase of hyaluronic acid by local bFGF injection was thought to contribute to the therapeutic effects on chronic vocal fold scarring.

Objectives. Endoscopic laryngopharyngeal surgery (ELPS) is a minimally invasive transoral surgery that was developed to treat superficial larygo-pharyngeal cancer, in which a mucosal lesion is resected transorally while preserving deeper structures by subepithelial injection. The purpose of this retrospective study is to evaluate voice outcome in patients who underwent ELPS for superficial hypopharyngeal cancer. As important structures in producing voice, such as in­trinsic laryngeal muscles, their fascia, and recurrent laryngeal nerve, are located in the medial side of the piriform si­nus and the postcricoid region of the hypopharynx, we focused on patients with cancer lesions involving these re­gions. Methods. From April 2010 to March 2011, 25 consecutive patients with superficial laryngopharyngeal cancer were treated with ELPS at Kyoto University Hospital. Among the 25 patients, 11 patients with cancer lesions on the medial side of the piriform sinus or the postcricoid area were studied. Preoperative and postoperative voice functions including maximum phonation time (MPT), mean flow rate (MFR), jitter, shimmer, soft phonation index (SPI), and noise-to-harmonic ratio (NHR), were compared retrospectively. Results. Five of 11 cancer lesions had submucosal invasion and no lesion had invaded the muscular layer pathologically. T stage was classified as Tis in 5 cases, T1 in 4 cases, and T2 in 2 cases. All lesions involved the medial side of the piri­form sinus and 2 also involved the postcricoid area. Vocal fold movement was normal in all cases after the surgery. Average preoperative and postoperative values for MPT, MFR, jitter, shimmer, SPI, and NHR, were 22.7 seconds and 23.4 seconds, 165 mL/sec and 150 mL/sec, 1.53% and 1.77%, 3.82% and 5.17%, 35.5 and 36.6, and 0.13% and 0.14%, respectively. There was no statistical difference between preoperative and postoperative data for all values ex­amined. Conclusion. ELPS is useful in preserving voice function in the treatment of superficial hypopharyngeal cancer. Preserving the deeper structures including intrinsic muscles and their fascia may be important for preserving voice function as long as the lesions are superficial.

Transoral surgery is a less invasive treatment that is becoming a major strategy in the treatment of laryngo-pharyngeal cancer. It is a minimally invasive approach that has no skin incision and limits the extent of tissue dissection, disruption of speech and swallowing muscles, blood loss, damage to major neurovascular structures, and injury to normal tissue. Transoral approaches to the laryngo-pharynx, except for early glottis cancer, had been limited traditionally to tumors that can be observed directly and manipulated with standard instrumentation and lighting. Since the 1990s, transoral laser microsurgery (TLM) has been used as an organ preservation strategy with good oncological control and good functional results, although it has not been widely used because of its technical difficulty. Recently, transoral robotic surgery (TORS) is becoming popular as a new treatment modality for laryngo-pharyngeal cancer, and surgical robots are used widely in the world since United States FDA approval in 2009. In spite of the global spread of TORS, it has not been approved by the Japan FDA, which has led to the development of other low-cost transoral surgical techniques in Japan. Transoral videolaryngoscopic surgery (TOVS) was developed as a new transoral surgery system for laryngo-pharyngeal lesions to address the problems of TLM. In TOVS, a rigid endoscope is used to visualize the surgical field instead of a microscope and the advantages of TOVS include the wide operative field and working space achieved using the distending laryngoscope and videolaryngoscope. Also, with the spread of narrow band imaging (NBI), endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD), which are widely used for superficial cancers in the gastrointestinal tract, have been applied for the superficial laryngo-pharyngeal cancer. Both EMR and ESD are performed mainly by gastroenterologists with a sharp dissector and magnifying endoscopy (ME)-NBI with minimal surgical margin. Endoscopic laryngo-pharyngeal surgery (ELPS) was developed to treat laryngo-pharyngeal superficial cancer by modifying the ESD procedure. The concept of ELPS is the same as that of ESD, however, the resection procedure is performed by a head and neck surgeon with both hands using a ME-NBI and rigid curved laryngo-pharyngoscope. These four procedures are low cost with similar oncological and functional outcomes to TORS. TORS may be less expensive than chemoradiotherapy, but the number of hospitals that can afford da Vinci surgical systems is limited. Even in the era of robotic surgery, these four procedures will be good options for laryngo-pharyngeal cancer.

当院では局所進行頭頸部扁平上皮癌（LA-SCCHN）において機能温存目的で導入化学療法（induction chemotherapy；ICT）を施行し，部分奏功（partial response；PR）以上になれば化学放射線治療（chemoradiotherapy；CRT）を施行している。Cetuximab（Cmab）導入以前はシスプラチン（CDDP）併用によるCRTを行っていたが，導入以降はCmab併用RT（bioradiotherapy；BRT）を行っている。今回，LA-SHCNにおいてICT後のCRTとBRTをretrospectiveに比較検討した。<br>対象は当科で一次治療を行ったLA-SCCHN 40例で，うちCRT群22 例，BRT群18例である。観察期間（中央値）はCRT群45.1ヶ月，BRT群17.3ヶ月である。治療完遂率はCRT群（CDDP≧160mg/m²）41％，BRT群（Cmab≧6cycle）83％，またCRT群のCDDP における相対的用量強度（relative dose intensity；RDI）は60％（144mg/m²）であり，BRTに比べるとCRTにおけるCDDPの完遂率は著明に不良であった。急性期有害事象（CTCAE v4にてGrade 3/4）はCRT群/BRT群において口腔粘膜炎36％/67％，放射線性皮膚炎9％/72％，嚥下障害23％/44％，誤嚥9％/44％といずれもBRT群に多い傾向があった。<br>ICT後の治療の選択については治療完遂率の面からはBRTが適当と考えられたが，CRTに比し高度な粘膜炎・皮膚炎が生じやすいため，十分な支持療法が必要と考えられた。

Background and study aims: Narrow band imaging (NBI) combined with magnifying endoscopy enables us to detect superficial laryngo-pharyngeal cancers, which are difficult to detect by standard endoscopy. Endoscopic laryngo-pharyngeal surgery (ELPS) is a technique developed to treat such lesions and the purpose of this study is to evaluate the usefulness of ELPS for superficial laryngo-pharyngeal cancer. Patients and methods: Seventy five consecutive patients with 104 fresh superficial laryngo-pharyngeal cancers are included in this study. Under general anesthesia, a specially-designed curved laryngoscope was inserted to create a working space in the pharyngeal lumen. A magnifying endoscope was inserted transorally to visualize the field and a head & neck surgeon dissected the lesion using the combination of the orally-inserted curved grasping forceps and electrosurgical needle knife in both hands. The safely, functional outcomes, and oncologic outcomes of ELPS were evaluated retrospectively. Results: Median operation time per lesion was 35 min. Post-operative bleeding occurred in 3 cases and temporal subcutaneous emphysema occurred in 10 cases. No vocal fold impairment occurred after surgery. The median fasting period was 2 days and all patients except one have a normal diet with no limitations. Local recurrence occurred in 1 case, and the 3-year overall survival rate and the 3-year disease specific survival rate was 90 % and 100 %, respectively. Conclusions: ELPS is a hybrid of head and neck surgery and gastrointestinal endoscopic treatment, and enjoys the merit of both procedures. ELPS makes it possible to perform minimally-invasive surgery, preserving both the swallowing and phonation functions.

Objective: The microflap technique is a standard procedure for the treatment of vocal fold polyps. Angiolytic laser surgery carried out under topical anesthesia is an alternative method for vocal polyp removal. However, it is not clear whether angiolytic laser surgery has the same effects on vocal outcomes as the microflap technique because of a lack of studies comparing both procedures. In the current study, vocal outcomes after both procedures were compared to clarify the effects of angiolytic laser surgery for vocal polyp removal. Methods: Vocal outcomes were reviewed for patients who underwent angiolytic laser surgery (n = 20, laser group) or microflap surgery (n = 34, microflap group) for vocal polyp removal. The data analyzed included patient and lesion characteristics, number of surgeries required for complete resolution, and aerodynamic and acoustic examinations before and after surgery. Results: In the laser surgery group, complete resolution of the lesion was achieved with a single procedure in 17 cases (85%) and with two procedures in 3 cases (15%). Postoperative aerodynamic and acoustic parameters demonstrated significant improvement compared to preoperative parameters in both the laser surgery group and the microflap surgery group. There were no significant differences in any postoperative aerodynamic and acoustic parameters between the two groups. Conclusion: The current retrospective study demonstrated that angiolytic laser surgery achieved complete resolution of vocal polyps within two procedures. Postoperative effects on aerodynamic and acoustic functions were similar to those after microflap surgery.

Objectives. Age-related voice change is characterized as weak, harsh, and breathy. These changes are caused by histologic alteration of the lamina propria of the vocal fold mucosa as well as atrophy of the thyroarytenoid muscle. Several therapeutic strategies involving laryngeal framework surgery and injection laryngoplasty have been tried, but effects have been limited. Vocal function exercises (VFE) have been used to treat age-related vocal fold atrophy although the effectiveness has been shown with limited analysis. The present study aims to determine the effectiveness of VFE for the treatment of aged atrophy using multidimensional analysis. Study Design. This is a retrospective study. Methods. Sixteen patients with vocal fold atrophy aged 65-81 years underwent voice therapy using VFE. Six patients with vocal fold atrophy aged 65-85 years were involved as a historical control group. The grade, roughness, breathiness, asthenia, strain (GRBAS) scale, stroboscopic examinations, aerodynamic assessment, acoustic analysis, and Voice Handicap Index-10 (VHI-10) were performed before and after VFE. Normalized mucosal wave amplitude (NMWA), normalized glottal gap (NGG), and bowing index (BI) were measured by image analysis during stroboscopic examinations. Results. After VFE, significant improvements were shown in GRBAS, maximum phonation time, jitter, NMWA, NGG, and VHI-10 although BI has not changed significantly. There were no significant improvements in the historical control. Conclusions. The data suggest that VFE produces significant improvement in subjective, objective, and patient self-evaluation and deserves further attention as a treatment for aged atrophy of the vocal fold. It was also suggested that VFE does not improve the vocal fold bowing but may improve muscular function during voicing.

Objectives/Hypothesis To examine if macroscopic classification with a magnifying gastrointestinal endoscope with narrow band imaging (ME-NBI) is useful in predicting pathological depth of tumor invasion in laryngo-pharyngeal cancer. Study Design Retrospective study. Methods Preoperative endoscopy reports and postoperative pathological reports on 139 laryngo-pharyngeal cancer lesions were retrospectively reviewed, and the association between macroscopic findings in the lesions and the depth of tumor invasion was analyzed statistically. Results The ratios of lesions macroscopically classified as 0-I (superficial and protruding), 0-IIa (slightly elevated), 0-IIb (true flat), 0-IIc (slightly depressed), and 0-III (superficial and excavated) in the preoperative endoscopy reports were 3%, 25%, 71%, 1%, and 0%, respectively. Regarding the depth of tumor invasion in the postoperative pathological reports, the ratios of lesions classified as EP (carcinoma in situ), SEP (tumor invades subepithelial layer), and MP (tumor invades muscularis propria) were 73%, 26%, and 1%, respectively. The ratios of subepithelial invasion or muscular invasion in 0-I, 0-IIa, and 0-IIb were 100%, 54%, and 14%, respectively, and showed significant difference (P<0.0001). Only one of 139 lesions invaded the muscular propria. Conclusions This study is the first one to show that macroscopic findings by ME-NBI predict the depth of tumor invasion in superficial laryngo-pharyngeal cancer. It was indicated that there is a little chance of muscular invasion if the lesion is endoscopically diagnosed as 0-I or 0-II. A new T stage classification based on the depth of tumor invasion may be needed in order to adapt the classification to include transoral surgery.

OBJECTIVE: Spasmodic dysphonia (SD) is a complex neurological communication disorder characterized by a choked, strain-strangled vocal quality with voice stoppages in phonation. Its symptoms are exacerbated by situations where communication failures are anticipated, and reduced when talking with animals or small children. Symptoms are also reduced following selected forms of treatment. It is reasonable to assume that surgical alteration reducing symptoms would also alter brain activity, though demonstration of such a phenomenon has not been documented. The objective of this study is to reveal brain activity of SD patients before and after surgical treatment.

Objectives/Hypothesis Vocal fold scarring is one of the most challenging laryngeal disorders to treat. Hyaluronic acid (HA) is the main component of lamina propria, and it plays an important role in proper vocal fold vibration and is also thought to be important in fetal wound healing without scarring. Although several animal models of vocal fold scarring have been reported, little is known about the way in which HA is maintained in vocal folds. The purpose of this study was to clarify the homeostasis of HA by examining the expression of hyaluronan synthase (Has) and hyaluronidase (Hyal), which produce and digest HA, respectively. Study Design Experimental prospective animal study. Methods Vocal fold stripping was performed on 38 Sprague-Dawley rats. Vocal fold tissue was collected at five time points (3 days-2 months). Expression of HA was examined by immunohistochemistry, and messenger RNA (mRNA) expression of Has and Hyal was examined by real-time polymerase chain reaction and in-situ hybridization. Results In scarred vocal folds, expression of Has1 and Has2 increased at day 3 together with expression of HA and returned to normal at 2 weeks. At 2 months, Has3 and Hyal3 mRNA showed higher expressions than normal. Conclusions Expression patterns of Has and Hyal genes differed between normal, acute-scarred, and chronic-scarred vocal folds, indicating the distinct roles of each enzyme in maintaining HA. Continuous upregulation of Has genes in the acute phase may be necessary to achieve scarless healing of vocal folds.

Objective: Treatment of vocal fold scarring remains challenging. We have previously reported the therapeutic effects of local injection of basic fibroblast growth factor (bFGF) in animal models and humans. A novel collagen/gelatin sponge (CGS) is capable of sustained release of bFGF, which compensates for its quick absorption in vivo, avoiding multiple injections. This study aimed to evaluate the biocompatibility and efficacy of the CGS in rat vocal fold fibroblasts prior to human trials. Methods: Fibroblasts extracted from Sprague-Dawley rat vocal folds were seeded onto a CGS and then cultivated with bFGF at concentrations of 0, 10, and 100 ng/mL. Vocal fold fibroblast morphology, adhesion, proliferation, and gene expression were measured under these 3-dimensional conditions. Results: Cells adhered to the CGS from day 1. Although no significant differences in cell morphology were detected, cell proliferation was accelerated by bFGF administration. Expression of endogenous bFGF and hepatocyte growth factor was significantly up-regulated at 10 ng/mL bFGF. The expression of procollagen I and procollagen III was significantly suppressed, whereas HAS-1 and HAS-2 were up-regulated at 10 and 100 ng/mL bFGF. Conclusion: The collagen/gelatin sponge is biocompatible with vocal fold fibroblasts and may be useful as a bFGF drug delivery system for the treatment of scarred vocal folds.

Conclusions: Distant metastasis was a major pattern of recurrence after postoperative radiotherapy (PORT) for squamous cell carcinoma (SCC) of the oropharynx, hypopharynx, and larynx. PORT provided good loco-regional control, with tolerable toxicities. Advanced pT and pN were unfavorable prognostic factors. Objective: To determine the clinical outcomes, and the patterns and risk factors for recurrence of SCCs of the oropharynx, hypopharynx, and larynx treated with surgery and PORT. Methods: We retrospectively reviewed 84 patients who received PORT after definitive surgery for SCC of the oropharynx, hypopharynx, or larynx between 2000 and 2010. The primary sites were the oropharynx in 25 patients, hypopharynx in 47 patients, and larynx in 12 patients. Results: The 3-year overall survival (OS), progression-free survival (PFS), and loco-regional control (LRC) rates were 64.9%, 56.7%, and 92.1%, respectively. Recurrences were observed in 27 patients: 6 patients had loco-regional recurrence and 23 patients developed distant metastasis. On multivariate analysis, pT4 and pN2c-N3 displayed significantly worse effects on OS (p = 0.02 and p < 0.01, respectively) and PFS (p = 0.02 and p < 0.001, respectively). In the acute phase, 12 patients experienced grade 3 or 4 toxicities. There were no grade 5 toxicities. Late grade 3 toxicity developed in six patients and no grade 4 or 5 toxicities were observed.

Objectives/Hypothesis: Vocal fold scarring presents therapeutic challenges. Recently, cell therapy with mesenchymal stromal cells has become a promising approach. The aim of this study was to compare the therapeutic potential of adiposederived stem cells (ASC) with bone marrow-derived stem cells (BMSC) for vocal fold regeneration.

Objectives/Hypothesis: Reactive oxygen species (ROS) are associated with aging. Astaxanthin (AST) is a strong antioxidant and has been reported to prevent various ROS-induced diseases. In the current study, we investigated the effect of AST on age-associated histological and mRNA changes of vocal folds. Study Design: Prospective animal experiment with control. Methods: Six-month-old Sprague-Dawley rats were fed on a normal powder diet with 0.01% (w/w) AST (aged AST-treated group) or without AST (aged sham-treated group). After 12 months of feeding, the larynges were harvested for histology, immunohistochemical detection of 4-hydroxy-2-nonenal (4-HNE), and quantitative real-time polymerase chain reaction for basic fibroblast growth factor (bFGF) and hepatocyte growth factor (HGF). Thirteen-week-old rats were used as a young control group (young group). Results: The expression of 4-HNE, an oxidative stress marker, significantly increased in the two aged groups compared with the young group. Histological examination showed that the deposition of hyaluronic acid in the lamina propria (LP) was significantly reduced in the aged sham-treated group compared with the young group, but no significant difference was observed between the aged AST-treated group and the young group. There were no significant differences in the mRNA expression of bFGF and HGF between the aged AST-treated group and the young group, although the expression of these genes was significantly reduced in the aged sham-treated group as compared with the young group. Conclusions: These results suggest that AST has the potential to attenuate age-associated changes of vocal folds.

Objectives/Hypothesis Previous animal studies demonstrated that hepatocyte growth factor (HGF) has the potential to regenerate scarred vocal folds. In addition, HGF is now produced under a good manufacturing practice (GMP) procedure. Therefore, human clinical trials of HGF are warranted in patients with vocal fold scarring. In the current study, we investigated the pharmacokinetics and the local tissue responses of HGF administered to rat vocal folds. Study Design Prospective animal experiment. Methods Five μg of recombinant human HGF was administered to the vocal folds of Sprague-Dawley rats (n = 60) using a microsyringe. The concentration of HGF in larynges and blood was investigated by enzyme-linked immunosorbent assay. To evaluate the local tissue responses caused by HGF administration, endoscopic and histological examinations were performed. Results HGF concentration in the larynges was 50.1 μg/g tissue 5 minutes after administration. The concentration decreased rapidly to 1.71 μg/g tissue at 12 hours after administration and to 0.29 ng/g tissue at 24 hours after administration. Seven days after administration, HGF concentration was minimal in one-half of the cases and was not detected in the other cases. Transmission of HGF to blood was detected in two of six cases at 5 minutes after administration, but was no longer detected 12 hours later. Endoscopic and histological examinations revealed no edema or erythema of the vocal folds in any of the cases. Conclusions The current results contribute to the safety and pharmacokinetic management of future clinical trials using HGF administered to vocal folds. Level of Evidence N/A. © 2014 The American Laryngological, Rhinological and Otological Society, Inc.

音声障害と診断した職業的歌唱者9例(男5例、女4例、平均53.3歳)に音声治療を実施し、その効果について検討した。疾患の内訳は声帯結節2名、声帯瘢痕2名、声帯萎縮3名、過緊張性発声障害2名で、治療は口腔前部の共鳴を意識したチューブ発声、Vocal Function Exercises、Lessac-Madsen Resonant Voice Therapyを中心に、2〜7ヵ月間行った。その結果、内視鏡所見は全例改善を認め、聴覚心理的評価(GRBAS尺度)の5項目合算値は治療前平均7.9から治療後5.8に、自覚的評価(VHI-10)は14.9点から6.6点に減少し、有意な改善を認めた。空気力学的検査では最長発声持続時間が14秒から21.4秒と有意に延長し、声の強さも増大した。音声フォルマントを評価するための周波数解析では、第3、第4フォルマントの位置が3000Hz付近に集中する傾向となり、F3-F4間距離は短縮した。