Pathogenesis of Reinke's Edema of the Vocal Fold.

OBJECTIVES: The most frequent etiologic factor of Reinke's edema (RE) is considered to be smoking. However, the mechanism for the onset and development of the disease remains unclear. Hypoxia-inducible factor-1α (HIF-1α) is an oxygen-dependent transcriptional activator which plays crucial roles in angiogenesis in hypoxic microenvironments. HIF-1α induces the expression of vascular endothelial growth factor (VEGF) which involves angiogenesis and enhances vascular permeability. This study investigated the roles of HIF-1α in the pathogenesis of RE. METHODS: Surgical specimens of RE from patients who underwent endolaryngeal microsurgery were used. Normal vocal folds were used as a control group. Expression of HIF-1α and VEGF was analyzed by immunohistochemistry. Three-dimensional fine structures of the vessels in RE were investigated using correlative light and electron microscopy (CLEM) technique. RESULTS: HIF-1α and VEGF were broadly expressed in the stromal, inflammatory, and endothelial cells in the lamina propria of the vocal fold of RE. The expression of HIF-1α and VEGF of RE were significantly higher than in the lamina propria of the normal vocal fold mucosa. CLEM showed vascularization and telangiectasia and there were many dilated capillaries with thin endothelium not covered with pericytes indicating the vessels were fragile. CONCLUSION: Transcription factor HIF-1α and induced VEGF likely play roles in the pathogenesis of RE. And increased vascular permeability with fragile vessels in angiogenesis is likely to be an etiology of RE. Transcription factor HIF-1α and induced VEGF are potential therapeutic targets for RE. LEVEL OF EVIDENCE: NA Laryngoscope, 134:1785-1791, 2024.

Additional effect of anthracycline in preoperative chemotherapy with a sequential anthracycline­containing regimen preceded by pertuzumab, trastuzumab and docetaxel combination therapy.

The proper use of anthracycline-containing regimens in combination with anti-HER2-targeted therapy in a neoadjuvant setting for patients with HER2-positive breast cancer has not been resolved. Regimens preceded by anthracyclines have become the standard of care, and although the order has no significant impact on HER2-negative breast cancer, it is inconclusive as to whether a taxane-first sequence would have a similar effect on HER2-positive breast cancer. The present study aimed to investigate the benefit of a taxane-first sequence and of adriamycin and cyclophosphamide (AC) in patients with non-clinical complete response (non-cCR) to pertuzumab, trastuzumab and docetaxel (PTD). The present single-center prospective observational study was performed to investigate PTD followed by AC, and aimed to clarify the cCR rate after PTD alone and the pathological clinical response (pCR) rate after subsequent AC in patients without cCR after PTD alone. A total 24 patients were analyzed; of these, 14 achieved pCR (pCR rate, 58.3%). While four of 14 patients (28.6%) in the intention-to-treat population achieved pCR, nine of 14 patients (64.3%) achieved pCR with AC but not cCR after PTD. The median tumor reduction rate after four cycles of PTD was 58.9% (range, 20.8-100%) in all 24 patients, whereas the reduction rate after PTD-AC was 76.9% (range, 31.1-100%). Cardiac serious adverse events occurred in three patients (12.5%). In conclusion, a high pCR rate was observed for the taxane-first sequence. Patients were highly responsive to PTD, but some cases achieved additional antitumor effects after AC, which resulted in pCR without cCR after PTD alone. Since cardiotoxicity remains a significant problem, a higher risk-benefit treatment strategy is required to aim for AC omission. Trial registration number: UMIN000046338, name of registry: UMIN-CTR, date of registration: December 10, 2021.

Vascularity in the macula flava of human vocal fold as a stem cell niche.

OBJECTIVES: There is growing evidence that the maculae flavae of the human vocal fold are a stem cell niche, which is a microenvironment nurturing tissue stem cells. This study investigated the microenvironment, especially vascularity, in the maculae flavae of the human vocal fold. METHODS: Three normal human adult, three normal newborn vocal folds obtained from autopsy cases and three surgical specimens of glottic carcinoma were investigated using light and electron microscopy. For scanning electron microscopy, a chemical digestion method (modified sodium hydroxide maceration method) was used to observe the inner 3-dimensional structure of the macula flava. RESULTS: Capillaries ran around the anterior and posterior maculae flavae in adults and newborns. However, there was no vascularity in the maculae flavae of the vocal fold. The inner 3-dimensional electron microscopic structure of the macula flava showed there were no blood vessels in the maculae flavae of the vocal fold. Glottic carcinoma (squamous cell carcinoma) surrounded and was in contact with the macula flava, however, the carcinoma did not invade the macula flava indicating there was no vascular supply into the macula flava from the surrounding tissue. CONCLUSIONS: There was no vascularity in the anterior and posterior maculae flavae in the human adult and newborn vocal folds. The present study is consistent with the hypothesis that the hypoxic microenvironment in the maculae flavae of the adult and newborn vocal fold as a stem cell niche is likely favorable to maintaining the stemness and undifferentiated states of the tissue stem cells in the stem cell system.

Long-Term Effects of Fat Injection Laryngoplasty in Relation to the Injected Fat Volume in Patients With Unilateral Vocal Fold Paralysis.

OBJECTIVE: To evaluate the improvements in vocal function and glottal form before and after autologous fat injection laryngoplasty in relation to the injected total fat volume in patients with unilateral vocal fold paralysis. DESIGN: Clinical study. METHODS: Seventy-three patients with unilateral vocal fold paralysis received fat injection laryngoplasty and were divided into low-volume injection (<3 mL; average, 2.0 mL) and high-volume injection (≥3 mL; average, 4.3 mL) groups. Voice function before and after fat injection laryngoplasty were examined by aerodynamics evaluations, pitch and intensity measurements, and acoustic analyses. The glottal form before and after fat injection laryngoplasty was determined by measuring the ratio of vocal fold bowing (bowing ratio) and the ratio of lengths between bilateral vocal process (width ratio) at an easy phonation under laryngeal endoscopic examination. The postoperative parameters were evaluated for a median period of four years after fat injection laryngoplasty. The differences between pre- and postoperative parameters were examined separately for each group by the paired t-test. For each variable, a comparison of the effects of surgery was conducted using an analysis of covariance model with the change between the pre- and postoperative values as a dependent variable and the preoperative value as a covariate. RESULTS: In both groups, all parameters of voice function and glottal form after surgery significantly improved in comparison to those before surgery. Maximum phonation time, amplitude perturbation quotient, and normalized noise energy for 0 to 4 kHz in the high-volume group improved more significantly in comparison to those in the low-volume group. CONCLUSIONS: As a rough guide for males, injection of more than 3 mL of autologous fat to the vocal muscle layer is recommended for reliable improvement of voice function in patients with unilateral vocal fold paralysis.

Laryngeal spaces in the newborn larynx.

OBJECTIVES: Distributions of laryngeal spaces are important in understanding their functional significance. However, laryngeal spaces in the newborn larynx are enigmatic. METHODS: Five normal human newborn larynges were investigated using whole organ serial section technique. RESULTS: The chief newborn laryngeal spaces were the preepiglottic space, the paraglottic space and the cricoid area. They consisted of an areolar tissue area composed of brown adipose tissue (immature adipose tissue) and loose elastic and collagen fibers. The newborn preepiglottic space was immature and occupied a small area anterior to the epiglottis. The epiglottis lied on a somewhat horizontal axis and was partially obscured behind the hyoid bone. The hyoid bone overlapped the thyroid cartilage, partially obscuring the superior thyroid notch. The thyroid cartilage was present close to the hyoid bone and the thyrohyoid membrane ran between the superior surface of the thyroid lamina, and not the anteroinferior, but the posteroinferior surface of the hyoid bone. The preepiglottic space was located anterior, lateral and posterolateral to the thyroepiglottic ligament. However, the preepiglottic space was located anterior to the epiglottic cartilage. As seen in adults, the paraglottic space existed medial to the lamina of each bilateral thyroid cartilage. Each bilateral cricoid area was located along not only the superomedial but also the medial portion of the cricoid arch on both sides. CONCLUSIONS: As the child grows, the preepiglottic space, occupying a small area anterior to the epiglottis, likely grows as the larynx descends and acquires the human adult vocal tract. From the functional histoanatomical point of view, the newborn laryngeal spaces appear to be favored for respiration and maintenance of a protective sphincter for the lower airway over phonation.

An Optimal Timing for Removing a Drain After Breast Surgery: A Systematic Review and Meta-Analysis.

BACKGROUND: In clinical practice, drains had been routinely used for reducing seroma formation after breast surgery. However, an optimal timing to remove drains does not identify yet. METHODS: This study aimed to compare the clinical outcome, such as seroma formation, surgical site infection (SSI), and a length of hospital stay between early removal and late removal. A systematic review was performed using PubMed, MEDLINE, and the Cochrane Library. Breast cancer patients who received surgery using drains were eligible. Those parameters were compared between early vs late removal. RESULTS: Eleven studies included in this meta-analysis. Seroma formation in the early removal group was significantly higher than the one in the late removal group (RR = 1.58: 95%CI [1.25-2.01], P = 0.0001), meanwhile no significant difference was found among the groups for SSI (RR = 0.82: 95%CI [0.51-1.31], P= 0.40). A length of hospital stay in the early removal group was also significantly shorter than late removal (RR -3.31: 95%CI [-5.13-1.49], P = 0.0004). CONCLUSIONS: Seroma formation was significantly higher in patients who had early drain removal. Conversely, SSI incidence was low, and early removal did not increase SSI incidence. In conclusion, early drain removal has no proved clinical benefit in these settings besides reduction of hospital stays.

Pathophysiology of current odontogenic maxillary sinusitis and endoscopic sinus surgery preceding dental treatment.

OBJECTIVE: The successful management of odontogenic maxillary sinusitis (OMS) involves a combination of medical treatment with dental surgery and/or endoscopic sinus surgery (ESS). However, there is no consensus for the optimal timing of ESS. Although several studies have emphasized dental surgery as the primary treatment modality for OMS, there is recent evidence to suggest that ESS alone may be an effective treatment approach. The purpose of this study is to retrospectively investigate the pathophysiology of the current intractable OMS and the role ESS, especially ESS preceding dental treatment, plays in its pathophysiology. METHODS: Ninety-seven adults (60 males and 37 females, 48 ± 12 years) who underwent ESS for intractable OMS were retrospectively examined. RESULTS: In a great deal of the cases (85 cases, 87.6%), causative teeth of OMS were periapical lesions after root canal treatment (endodontics). The root canal procedures were not sufficient; hence, the root-canal-treated teeth had periapical lesions causing OMS. In postoperative nasal endoscopy and cone-beam CT scans for all patients, the natural ostiums and the membranous portions of the maxillary sinuses were enlarged and the ostiomeatal complexes remained widely open. The ventilation and drainage of all patients' maxillary sinuses seemed to be successfully restored. Temporary acute sinusitis recurrence after primary ESS for OMS was observed in 10 cases (11.8%) when the patients caught a cold. However, since the natural ostium and the membranous portion of the maxillary sinuses and the ostiomeatal complexes remained widely open, antibiotic administration alone without dental treatment cured the temporary acute sinusitis. Regarding the causative teeth (endodontic treated teeth), in 83 out of 85 cases (97.6%), causative teeth were able to be preserved with only antibiotic treatment and without dental retreatment. In two cases, extraction of the teeth was necessary because the teeth became mobile. Regarding the causative teeth after dental restoration, in 2 out of 2 cases (100%), causative teeth were able to be preserved with antibiotic treatment alone. CONCLUSION: ESS is highly indicated for OMS requiring surgery. The treatment results of intractable OMS are exceptionally good once the ventilation and drainage of the maxillary sinus is successfully restored after surgery. Consequently, ESS can be considered the first-line therapy for intractable OMS caused by root canal treatment (endodontics) and dental restoration, followed by close dental follow-up and dental treatment when necessary.

Epithelium of the human vocal fold as a vibrating tissue.

OBJECTIVES: The human adult vocal fold mucosa, especially, superficial layer of the lamina propria (Reinke's space) has attracted notice as an important vibrating structure. However, fine structures of the stratified squamous epithelium of the human adult vocal fold, which is another histological component of the mucosa, remain enigmatic. METHODS: Three normal human adult vocal folds and epiglottises and three newborn vocal folds were investigated. Observations using transmission electron microscopy and light microscopy including immunohistochemistry were performed. RESULTS: The most obvious feature of the epithelium of the human adult vocal folds was that the intercellular spaces between adjacent epithelial cells were large (984 ± 186 nm) compared with the stratified squamous epithelium of the human adult epiglottis and the human newborn vocal fold. Even though intercellular spaces between adjacent epithelial cells of the human adult vocal fold were large, desmosomes at the junctions of two adjacent epithelial cells made firm intercellular adhesion. Tonofilaments composed of the bundles of intermediate filaments anchored to the desmosomes. Desmosomes formed a continuous cytoskeletal network throughout the epithelial cells and epithelium of the human adult vocal fold. In addition, a great deal of E-cadherin (adhesive glycoprotein) was present between epithelial cells especially the lower half of the stratified squamous epithelium of the human adult vocal fold. CONCLUSIONS: From the functional morphological point of view, stratified squamous epithelium of the human adult vocal fold seems to form a structural framework of tensile strength with pliability suitable structure for vibration.

Does our swallow go to sleep? Changes in swallow function during sleep and implications for symptoms.

PURPOSE OF REVIEW: Swallowing is a vital function and the clearance of the pharynx by deglutition, which removes matter that could be aspirated, and the respiratory phase patterns associated with deglutition are important in protecting the airways and lungs against aspiration. This article reviews swallowing and respiratory phase patterns associated with deglutition during sleep and their implications for pathophysiology. RECENT FINDINGS: During sleep, swallowing is infrequent and absent for long periods. The deeper the sleep stage, the lower the mean deglutition frequency. However, in healthy younger adults, sleep-related deglutition is almost always followed by arrested breathing and expiration, reducing the risk of aspiration. Deglutition is extremely infrequent as well as absent for long periods in the aged. Consequently, clearance of the pharynx and esophagus by deglutition was extremely reduced during sleep in the aged. Furthermore, respiratory phase patterns associated with deglutition displayed adverse patterns during sleep in the aged. SUMMARY: Due to the complexity of swallowing processes, many adverse health conditions can influence swallowing functions during sleep, especially in the aged. Sleep-related deglutition and respiratory phase patterns may adversely influence aspiration-related diseases such as aspiration pneumonia, especially in the aged not only with primary but also with secondary presbyphagia.

Histopathology of maxillary sinus mucosa with odontogenic maxillary sinusitis.

OBJECTIVE: Histopathology of the maxillary sinus mucosa with intractable odontogenic maxillary sinusitis (OMS) was investigated and the role endoscopic sinus surgery (ESS) plays in its pathophysiology was clarified. STUDY DESIGN: Histopathological analysis of the OMS mucosa. METHODS: Surgical specimens were obtained from 20 patients who underwent ESS for intractable OMS. For rigid endoscopic observation of the mucosae, a 70° rigid endoscope 4 mm in diameter with an attached high definition surgical camera was used. Histopathological analyses of the maxillary sinus mucosa were conducted by light and scanning electron microscopy. RESULTS: All the maxillary sinuses were filled, not with viscous, but with purulent secretions. The high-definition camera showed that the maxillary sinus mucosa had gyrus-like appearance. Light microscopic histopathological studies revealed that the surface of the maxillary sinus mucosa was convoluted. Light and scanning electron microscopic histopathological studies revealed that the ciliated cells of the epithelium had not decreased and their goblet cells were not hypertrophic, indicating that the damage of the ciliated columnar epithelium was not severe and they were not injured irreversibly. CONCLUSION: The ciliated columnar epithelium with intractable OMS was not severely damaged and not irreversibly injured. Hence, the pathophysiology of intractable OMS is one of the reasons why ESS is highly indicated for maxillary sinusitis requiring surgery and the treatment results are exceptionally good when the ventilation and drainage of the maxillary sinus is successfully restored after surgery. LEVEL OF EVIDENCE: NA.

Lateral pharyngeal flap with a double pedicle for repair of unilateral velopharyngeal insufficiency.

OBJECTIVES: Conventional pharyngeal flap surgery, which closes the median portion of the velopharynx, has been performed for dysarthria patients with velopharyngeal insufficiency (VPI). However, for VPI due to unilateral pharyngeal paralysis, median closing disrupts pharyngeal contraction of the unaffected side and allows pharyngeal pressure to escape through the nose at the lateral portion of the affected side during speech and swallowing. The purpose of this study was to evaluate the effectiveness of lateral pharyngeal flap (LPF) surgery for unilateral VPI. METHODS: Seven patients with unilateral VPI (five males and two females with an average age of 54 years) underwent LPF surgery combined with other transoral surgeries for dysphagia. The LPF surgical technique was as follows: after the laterocaudal-based pedicle flap of the soft palate and cranial-based pedicle flap of the posterior pharyngeal wall on the affected side were transorally elevated, each mucosal pedicle flap was sutured together. Functional oral intake scale (FOIS) scores and swallowing pressure before and after surgery were compared. RESULTS: Unilateral velopharyngeal closure preserved nasal breathing after LPF surgery in all patients. Rhinolalia aperta improved postoperatively in all patients except one. The mean FOIS scores were 2.3 preoperatively and 3.7, 5.3, and 5.9 at 2 weeks, 1 month, and 6 months postoperatively, respectively. The mean pressures significantly increased at the velopharynx (from 49±30mmHg to 92±45mmHg) and oropharynx (from 48±18mmHg to 66±15mmHg) six months after the surgery. CONCLUSION: LPF surgery leaving the unaffected side intact can be an effective surgical procedure for patients with unilateral VPI.

Endoscopic Sealing With a Polyglycolic Acid Sheet for Restoration of Vocal Fold Mucosa in Dogs.

OBJECTIVES/HYPOTHESIS: Voice outcomes of cordectomy for early glottic cancer are often poor due to vocal fold scarring and tissue defects. Improvements in this aspect could make cordectomy a more acceptable treatment option than radiotherapy. We hypothesized that a polyglycolic acid (PGA) sheet could be used to cover vocal fold defects. The present study aimed to prevent vocal fold scarring after cordectomy using the PGA sheet. STUDY DESIGN: Animal experiment. METHODS: Nine male beagles were divided into three groups including a control group (n = 3). Following cordectomy, the vocal fold defect was covered with the PGA sheet plus fibrin glue (PGA group; n = 3) or with the PGA sheet plus fibrin glue containing basic fibroblast growth factor (bFGF; the PGA-bFGF group, n = 3). Vocal folds were chronologically observed, and larynges were removed 6 months after surgery. Mucosal amplitude was measured using a high-speed camera, and histological analysis was performed. RESULTS: The re-epithelialization process was delayed in the PGA and PGA-bFGF groups compared with the control group. The mucosal amplitude was significantly more normalized and the thickness ratio significantly higher in the PGA and PGA-bFGF groups compared with the control group. The PGA-bFGF group had the highest elastic fiber density, followed by the PGA group and then the control group, with a significant difference between the PGA-bFGF and control groups. CONCLUSIONS: The PGA sheet plus fibrin glue could serve as an effective regenerative scaffold for reconstructing vocal fold morphology and function after cordectomy, with the potential benefit of establishing an endoscopic sealing method for vocal fold defects. LEVEL OF EVIDENCE: NA Laryngoscope, 130:E436-E443, 2020.

Heterogeneity of Stem Cells in the Human Vocal Fold Mucosa.

1. There is growing evidence to suggest that the cells in the maculae flavae are tissue stem cells of the human vocal fold and maculae flavae are a candidate for a stem cell niche. 2. The latest research shows that the cells in the human maculae flavae are involved in the metabolism of extracellular matrices that are essential for viscoelasticity in the human vocal fold mucosa as a vibrating tissue and are considered to be important cells in the growth, development, and aging of the human vocal fold mucosa. 3. Recent evidence has indicated that the cells including vocal fold stellate cells in the maculae flavae of the human vocal fold mucosa are a functionally heterogenous population. 4. The cells in the human maculae flavae possess proteins of all three germ layers, indicating that they are undifferentiated and have the ability of multipotency. 5. The cell division in the human adult maculae flavae is reflective of asymmetric self-renewal, and cultured cells form a colony-forming unit. Therefore, the phenomenon gives rise to the strong possibility that the cells in the human maculae flavae are putative stem cells. 6. Recent research has suggested that the cells in the human maculae flavae arise from the differentiation of bone marrow cells via peripheral circulation. 7. Cultured cell populations in the human maculae flavae are roughly divided into three groups by morphological features: cobblestone-like polygonal cells, vocal fold stellate cell-like cells, and fibroblast-like spindle cells. However, at the present state of our investigation, it is difficult to clarify the stem cell system and hierarchy of stem cells in the human maculae flavae. 8. Subpopulations of cells in the maculae flavae proliferate extremely slowly and retain stem cell properties. 9. Tension caused by phonation seems to regulate the behavior and heterogeneity of the cells (mechanical regulation) in the maculae flavae of the human vocal fold. 10. The putative stem cells in the maculae flavae appear to differentiate into other kind of cells in the surrounding tissue.

Distribution of label-retaining cells and their properties in the vocal fold mucosa.

OBJECTIVE: The latest research suggests cells in the maculae flavae (MFe) are putative stem cells of the vocal fold mucosa and the MFe are a candidate for a stem cell niche. Distribution and properties of label-retaining cells (LRCs) in the vocal fold mucosa were investigated. STUDY DESIGN: Histologic analysis of the rat vocal folds. METHODS: Oral administration of bromodeoxyuridine (BrdU) was given to rats and the LRCs in the vocal fold mucosa were observed by immunohistochemistry. Immunoreactivity to antibodies directed to BrdU, Ki67, cytokeratin, vimentin, glial fibrillary acidic protein, desmin, Sox17, CD34, CD45, Type I collagen, and CD44 was studied. Extracellular matrices around LRCs were observed by Alcian blue staining and hyaluronidase digestion study. RESULTS: LRCs were present in the MFe and were resting cells (G0-phase). They expressed epithelium, muscle, neural, and mesenchymal cell-associated intermediate filament proteins, and an endodermal marker, indicating cells in the MFe are undifferentiated and express proteins of all three germ layers. They expressed hematopoietic markers (CD34, CD45) and Type I collagen, which are the major markers of bone marrow derived circulating fibrocytes. The hyaluronan concentration in the MFe was high and the cells in the MFe expressed the surface hyaluronan receptor CD44, indicating that the MFe were a hyaluronan-rich matrix. CONCLUSION: LRCs reside in the MFe and MFe had a hyaluronan-rich matrix. The results of this study are consistent with the hypothesis that the cells in the MFe are putative stem cells and the MFe are a candidate for a stem cell niche. LEVEL OF EVIDENCE: N/A.

Pathological mechanisms of laryngeal papillomatosis based on laryngeal epithelial characteristics.

OBJECTIVES: Human papillomavirus (HPV) infects basal cells of the stratified squamous epithelium through micro epithelial trauma. However, laryngeal papillomatosis commonly appears in any site on the laryngeal mucosa not covered by stratified squamous epithelium. The purpose of this study is to clarify pathological mechanisms of laryngeal papillomatosis based on the characteristics of the laryngeal epithelium. STUDY DESIGN: Morphological and immunohistochemical study. METHODS: Larynges from one newborn and two adults were used. Morphological differences in the laryngeal squamo-ciliary junction (lSCJ) were compared to those in the cervical squamo-columnar junction (cSCJ) in a resected cervix uterus. Morphological characteristics of laryngeal epithelial distribution were also compared between the newborn and adult larynges. Immunohistochemical evaluations were performed using p63 (an epithelial stem-cell marker) and integrin-α6 (a cellular HPV receptor). RESULTS: Morphological differences were noted between the lSCJ and the cSCJ. The lSCJ was present in the adult, but not the newborn supraglottis. Goblet cells in the pseudostratified ciliated columnar epithelium were also found in the adult but not the newborn larynx. In addition, basal cells of the stratified squamous epithelium as well as the pseudostratified ciliated columnar epithelium expressed p63 and integrin-α6 in both newborn and adult larynges. CONCLUSIONS: HPV can infect any immature laryngeal epithelium with or without the lSCJ. Squamous metaplasia of pseudostratified ciliated columnar epithelium with a latent HPV infection can also cause tumorigenesis. LEVEL OF EVIDENCE: N/A.

Stable Tracheal Regeneration Using Organotypically Cultured Tissue Composed of Autologous Chondrocytes and Epithelial Cells in Beagles.

OBJECTIVES: In tracheal regeneration, the slow process of epithelialization is often a barrier to the stability and safety of the transplanted trachea. The aim of this study was to examine a new tracheal regeneration technique using organotypically cultured tissue composed of autologous cells. METHODS: Nine beagles were prepared. Chondrocytes from auricular cartilage and epithelial cells from buccal mucosa were isolated and cultured. Tissue-engineered cartilages were fabricated with chondrocytes at a density of 1 × 107 cells/mL (high-density group) and 1 × 106 cells/mL (low-density group). A fabricated epithelial cell sheet was laid on a poly(lactic-co-glycolic acid) block in atelocollagen gel containing the chondrocytes, and the organotypically cultured tissues were transplanted into a partially resected trachea. The control group had only the block transplanted. RESULTS: The tissue-engineered cartilages in the high-density group contained many viable chondrocytes and many cartilage matrices. The low-density group had abundant collagen fibers and no chondrocytes. Tracheal endoscopy revealed no deformation or atrophy at the transplant site in the high-density group. Histologically, partially hyaline cartilages covered with epithelium and lamina propria were found in the high-density group but not in the low-density and control groups. CONCLUSIONS: Stable tracheal regeneration was achieved using organotypically cultured tissue fabricated with autologous high-density chondrocytes and epithelial cells.

Differentiation potential of the cells in the macula flava of the human vocal fold mucosa.

The latest research suggests cells in the maculae flavae located at both ends of the lamina propria of the human vocal fold mucosa have stemness. This study investigated the differentiation potential of the cells in the maculae flavae of the human vocal fold mucosa. Four normal human adult vocal folds from surgical specimens were used. After extraction of the anterior maculae flavae located at the anterior end of the lamina propria of the human vocal fold mucosa under microscope, the maculae flavae were minced, cultured and proliferated in mesenchymal stem cell growth medium and morphological features were assessed. Cell surface markers were detected using flow cytometry. Cell differentiation into adipogenic, chondrogenic and osteogenic lineages was performed. Cell's differentiation potential was assessed using a human pluripotent stem cell functional identification kit and immunohistochemistry. Subcultured cells formed a colony-forming unit. Subcultured cells expressed CD90, CD105 and CD73 and lacked expression of CD45, CD34, CD11b, CD19 and HLA-DR. They differentiated into adipogenic, chondrogenic and osteogenic lineages. Consequently, the cell features in the maculae flavae meet the minimal criteria defining mesenchymal stromal cells. In addition, subcultured cells differentiated into ectoderm, mesoderm and endoderm and expressed stage-specific embryonic antigen 3 (SSEA-3). The results of this study are consistent with the hypothesis that the cells in the maculae flavae in the lamina propria of the human vocal fold mucosa are putative stem cells.

Study of Salt Precipitation in Polymer Electrolytes Based on Poly(ethylene oxide) and EMImTf Ionic Liquid.

In solidlike polymer electrolytes, salt precipitation (SP) followed by the occurrence of neutral ion pairs in polymer electrolytes is known to deteriorate ionic conductivity, but has not been the subject of intense study so far. Here, the mechanism of SP is studied for a polymer electrolyte consisting of poly(ethylene oxide) (PEO) and ionic liquid salt of 1-ethyl-3-methylimidazolium trifluoromethanesulfonate (EMImTf), which is one of the promising prototype systems because of its technological relevance. It is found that Ångstrom-scale open spaces in the amorphous matrix sensitively change in response to the release of organic cation from PEO polymer chains as well as SP in the Arrhenius manner. The cation release, triggering off ion-pair formation, takes place at the temperature by far lower than that of SP with an activation energy of ∼0.2 eV, whereas SP involves an energy cost of ∼0.4 eV. The results suggest that SP in the PEO-EMImTf complex is mechanistically explained from the viewpoint of the abovementioned two processes, that is, cation release from the present PEO-EMImTf complex and ion pairing.

Augmentation surgery on the cartilaginous portion of the vocal fold in a patient with cricoarytenoid joint ankylosis.

Surgical management of cricoarytenoid joint (CAJ) ankylosis is challenging and has the risk of worsening voice quality. In the present case, augmentation surgery was performed on the cartilaginous portion of the vocal fold in a patient with CAJ ankylosis. A 24-year-old man sustained blunt trauma to the anterior neck three years prior to developing severe breathiness. Posterior glottal insufficiency resulting from lateral fixation of the right vocal fold was observed during phonation under laryngoscopy. In addition, electromyography and CT scan revealed severe ankylosis of the right CAJ. Type I thyroplasty performed on the right vocal fold did not improve postoperative vocal function. Therefore, augmentation surgery on the cartilaginous portion of the right vocal fold was performed via endolaryngeal microsurgery under general anesthesia with jet ventilation. A piece of temporalis fascia was autotransplanted into the submucosal space created at the posterior cartilaginous portion of the right vocal fold. This resulted in the narrowing of the posterior glottal gap during phonation, leading to improvement in hoarseness. Microsurgical management with autologous fascia augmentation of the cartilaginous portion of the vocal fold can be effective in patients with lateral vocal fold fixation due to CAJ ankylosis.

Use of dynamic MRI during swallowing to assess carotid artery invasion by neck metastasis.

BACKGROUND: The effectiveness of dynamic MRI in evaluating the relationship between metastatic lymph nodes and the carotid artery was investigated. METHODS: Thirty-two patients with metastatic lymph nodes, possibly adherent to the carotid artery, were evaluated with dynamic MRI before surgery. Consecutive axial and oblique images were obtained during swallowing. The displacement rate of the target carotid artery to the contralateral carotid artery and the low-intensity stripe between the metastatic lymph nodes and the carotid artery wall were compared with the surgical findings. RESULTS: A displacement rate > 50% indicated resectable metastatic lymph nodes. Low-intensity stripe was present in 65% of patients and indicated no invasion; 82% of patients without low-intensity stripe had resectable metastatic lymph nodes. The others without low-intensity stripe required carotid artery resection due to malignant invasion. The accuracy rate, sensitivity, and specificity were 78%, 83%, and 100%, respectively. CONCLUSION: Dynamic MRI during swallowing is useful for assessing suspected carotid artery involvement in patients with metastatic lymph nodes to achieve maximal safe resection.