Search

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.

Tissue stem cells in the maculae flavae (a stem cell niche) of the human vocal fold form colonies in vivo like stem cells in vitro. However, the roles of colony-forming aggregated cells in the maculae flavae in vivo have not yet been determined. This study investigated the glycolysis, of the colony-forming aggregated cells in the maculae flavae of the human newborn vocal fold in vivo.Three normal newborn vocal folds were investigated under light microscopy with immunohistochemistry and transmission electron microscopy.Colony-forming aggregated cells in the newborn maculae flavae strongly expressed glucose transporter-1 and glycolytic enzymes (hexokinase II, glyceraldehyde-3-phosphate dehydrogenase and lactate dehydrogenase A). The colony-forming aggregated cells did not express phosphofructokinase-1 (rate-limiting enzyme of regular glucose metabolism pathway) but expressed glucose-6-phosphate dehydrogenase (rate-limiting enzyme) indicating the cells relied more on the pentose phosphate pathway. The colony-forming aggregated cells' strong expression of lactate dehydrogenase A indicated that they rely more on anaerobic glycolysis in an anaerobic microenvironment. Mitochondrial cristae of the colony-forming aggregated cells in the newborn maculae flavae were sparse. Consequently, the microstructural features of the mitochondria suggested that their metabolic activity and oxidative phosphorylation were low.The colony-forming aggregated cells in the maculae flavae of the newborn vocal fold seemed to rely more on anaerobic glycolysis using the pentose phosphate pathway for energy supply in vivo. Microstructural features of the mitochondria and the glycolytic enzyme expression of the colony-forming aggregated cells suggested that the oxidative phosphorylation activity was low. Already at birth, in the anaerobic microenvironment of the macular flavae in vivo, there is likely a complex cross-talk regarding metabolism between the colony-forming aggregated cells along the adhesion machinery and chemical signaling pathways which reduces toxic oxygen species and is favorable to maintaining the stemness and undifferentiated states of the tissue stem cells.

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.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.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.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.

Objectives: Selective radiotherapy and concomitant intra-arterial cisplatin infusion (m-RADPLAT) with a lower cisplatin dosage have been performed for organ and function preservation in patients with locally advanced squamous cell carcinoma of the larynx (SCC-L), and results showing a lower rate of adverse events have been reported. This study evaluated the treatment outcomes of patients with T3N0 glottic SCC-L with or without vocal fold fixation (VFF) who were treated with m-RADPLAT. Methods: We retrospectively reviewed the data of 33 patients with T3N0 SCC-L who received m-RADPLAT. Results: The vocal fold in patients with VFF 3 months after completing m-RADPLAT resumed normal movement in 15 patients (83%) and persisted fixation in 3 (17%). The 3-year local control, laryngeal cancer-specific survival, and overall survival rates of patients with or without VFF were 88.9% and 86.7%, 94.1% and 93.3%, and 88.9% and 86.7%, respectively. Additionally, the 3-year freedom from laryngectomy, laryngectomy-free survival, and laryngo-esophageal dysfunction-free survival rates of patients with or without VFF were 94.4% and 86.7%, 88.9% and 73.3%, and 83.3% and 73.3%, respectively. Grade 3 or higher toxicities were observed in all patients: leukopenia in 4 patients (12%), neutropenia in 5 (15%), anemia in 2 (6%), thrombocytopenia in 3 (9%), and mucositis in 2 (6%). Conclusions: This study demonstrated that m-RADPLAT yielded VFF improvement and a favorable survival while maintaining laryngeal function not only in patients with T3N0 glottic SCC-L without VFF but also in patients with VFF.

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.

Objective The clearance of the pharynx by deglutition and the respiratory phase patterns associated with deglutition are important in protecting airways and lungs against aspiration. The deglutition and respiratory phase patterns during sleep in patients (without swallowing disorders while awake) with obstructive sleep apnea (OSA) precipitating recurrent intractable aspiration pneumonia were investigated. Methods After videoendoscopic and videofluorographic examinations of swallowing showed subjects had no swallowing disorders while awake, two adults with recurrent intractable aspiration pneumonia precipitated by severe OSA were examined via time-matched digital recordings of polysomnography and surface electromyography of the muscles (thyrohyoid and suprahyoid muscles) related to swallowing and compared with the same patients before and under CPAP therapy. Results CPAP therapy cured recurrent intractable aspiration pneumonia. Swallows following and/or followed by inspiration (uncoordinated deglutition with respiration), which were frequently observed before CPAP therapy, were markedly reduced under CPAP therapy. On the other hand, swallows following and/or followed by expiration (coordinated deglutition with respiration) markedly increased under CPAP therapy. Deglutition was related to the sleep stage. The deeper the sleep stage, the lower the deglutition frequency. Before and under CPAP therapy, swallowing was infrequent and absent for long periods. However, respiratory phase patterns associated with sleep-related deglutition in patients with OSA under CPAP therapy markedly improved. Conclusions In patients (without swallowing disorders while awake) with OSA precipitating recurrent intractable aspiration pneumonia, the high rate of uncoordinated deglutition with respiration (swallows following and/or followed by inspiration) during sleep were markedly reduced and the rate of coordinated deglutition with respiration (swallows following and/or followed by expiration) was markedly increased under CPAP therapy. Sleep-related deglutition and respiratory phase patterns are likely to adversely influence aspiration pneumonia in patients with OSA. CPAP therapy improved not only apnea-hypopnea during sleep and sleep quality but also sleep-related deglutition, especially respiratory phase patterns associated with deglutition in patients with OSA. CPAP therapy may decrease the risk of aspiration and greatly improve aspiration-related diseases such as aspiration pneumonia.

There is growing evidence that the cells in the maculae flavae are tissue stem cells and the maculae flavae are a stem cell niche of the human vocal fold mucosa. This study investigated the metabolic activity, especially glycolysis, of the tissue stem cells in the maculae flavae of the human newborn vocal fold.Three normal human newborn vocal folds obtained from autopsy cases were investigated using immunohistochemistry.Among the three phenotypes of cells (cobblestone-like polygonal cells, vocal fold stellate cell-like cells and fibroblast-like spindle cells) in the newborn maculae flavae, a small number of cobblestone-like polygonal cells strongly expressed glucose transporter-1. All three phenotypes of cells in the newborn maculae flavae expressed glycolytic enzymes (hexokinase II, glyceraldehyde-3-phosphate dehydrogenase and lactate dehydrogenase A). The cells did not express phosphofructokinase-1 (rate-limiting enzyme of regular glucose metabolism pathway) but sparsely express glucose-6-phosphate dehydrogenase (rate-limiting enzyme) indicating the cells relied more on the pentose phosphate pathway. The cells' expression of lactate dehydrogenase A suggests the maculae flavae of the newborn vocal fold is likely to be an anaerobic microenvironment where cells perform anaerobic glycolysis.The present study is consistent with the hypothesis that the tissue stem cells in the maculae flavae of the newborn vocal fold seem to rely more on anaerobic glycolysis, especially by the pentose phosphate pathway, for energy supply. Already at birth, the metabolism of the tissue stem cells in the maculae flavae of the newborn vocal fold is likely to prevent the formation of toxic reactive oxygen species and is likely favorable to maintaining the stemness and undifferentiated states of the tissue stem cells in the stem cell system.

Cells in the maculae flavae (MFe) are inferred to be involved in the metabolism of extracellular matrices of the human vocal fold mucosa. The latest research has supported the hypothesis that the tension caused by phonation (vocal fold vibration) regulates the behavior of these cells in the MFe of the human vocal fold. Tensile and compressive strains have direct effects on cell morphology and structure including changes in cytoskeletal structure and organization. Cytoskeletons are one of the structures which play a role as mechanoreceptors for the cells. The microstructure of the intermediate filaments and the expression of their proteins were investigated regarding the cells in the MFe of the human vocal fold unphonated over a decade. The adult vocal fold mucosa of a 64-year-old male with cerebral hemorrhage unphonated for 11 years was investigated by immunohistochemistry and electron microscopy. The intermediate filaments in the cytoplasm of the cells had become fewer in number. And the expression of their characteristic proteins (vimentin, desmin, GFAP) was also reduced. The results of this study are consistent with the hypothesis that mechanotransduction caused by vocal fold vibration could possibly be a factor in regulating the function and fate of the cells in the MFe.

Objectives There is growing evidence that the cells in the maculae flavae (MFe) are tissue stem cells and the MFe are a stem cell niche of the human vocal fold mucosa. Heterogeneity and hierarchy of tissue stem cells in the MFe of newborn vocal fold were investigated in vivo. Study design Histologic analysis of the human vocal folds. Methods Five normal human newborn vocal folds were investigated under transmission electron microscopy and light microscopy. Results Cobblestone-like polygonal cells, vocal fold stellate cell-like cells, and fibroblast-like spindle cells were intermingled in the newborn MFe in vivo, indicating that the cells in the MFe had heterogeneity. However, cobblestone-like polygonal cells were predominant. Free ribosomes were well developed in the cytoplasm. The cells in some cases formed gap junctions with each other. The cells in some cases were attached to other cells and formed cell junctions with each other. These findings indicated cells in the newborn maculae flavae possessed features of mesenchymal cells (cells in mesenchyme). Colony-forming-unit-like cell aggregate was observed, indicating the cells in the newborn MFe had stemness. The cobblestone-like polygonal cells expressed SSEA-3 (a human pluripotent stem cell marker), indicating they were at the top of a cellular hierarchy in the stem cell system. Conclusions The cells in the MFe of the human newborn vocal fold mucosa had heterogeneity and hierarchy in the stem cell system in vivo. At birth, newborn maculae flavae are ready to start the growth of the vocal fold mucosa as a vibrating tissue.

A lordotic curve of the cervical spine in the aged is a physiological curvature of the cervical spine. The swallowing disorder precipitated by lordosis of the cervical spine in the aged, the swallowing function and intervention were reported on. An 86-year-old woman complained of swallowing difficulty for a few months. A lordotic curve (physiological curvature) of the cervical spine was observed. In the neutral neck position, the cervical lordotic angle was 29° using the Cobb C2-C7 method. When the lordotic curve of the cervical spine was intentionally straightened, the lordotic angle became 0°, the laryngeal elevation changed from 0.5 times the height of a cervical vertebra to 1.75 times, the laryngeal elevation delay time changed from 0.5 seconds to 0.23, the percent laryngeal elevation changed from 50% to 72% and pharyngeal transit time changed from 0.83 seconds to 0.75. Lordosis of the cervical spine inhibited laryngeal elevation and influenced the swallowing function. In cases in which lordotic curvature of the cervical spine adversely influences the swallowing function in the aged, rehabilitation to manage the lordosis of the cervical spine is useful. For the purpose of effective intervention, not only diagnostic but also therapeutic videofluorographic examination of swallowing is very important.

Background: Respiratory phase patterns associated with deglutition and clearance of pharynx by deglutition are important in protecting airways and lungs against aspiration.Aims/objectives: Sleep-re...

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.

An adequate understanding of the evolution of the larynx presumably clarify the physiology and functional histoanatomy of the present-day human organ. This study investigated the comparative histoanatomy of the epiglottis and preepiglottic space of the lemur larynx (a non-human primate without vocal tract).Two normal adult ring-tailed lemur larynges obtained from natural death were investigated. The whole organ serial section technique was employed.The histologic structures of the lemur epiglottis and preepiglottic space differed considerably from that of human adults. The lemur epiglottis was proportionally thick and vertical. It was connected to the thyroid cartilage anteroinferiorly without an intervening thyroepiglottic ligament and to the hyoid bone anteriorly with intervening large bundles of collagen fibers, indicating that the lemur epiglottis does not play the role of retroflection. The lemur larynges did not have a preepiglottic space. These findings also reflect the fact that lemurs do not have a descended larynx and do not acquire the pharyngeal space of the vocal tract. The lemur epiglottis was composed of fibrocartilage, adipose tissue and a small amount of elastic cartilage covered with mucosa (lamina propria and pseudostratified ciliated columnar epithelium). The histologic findings also indicate that the lemur epiglottis is not flexible and does not play the role of retroflection.The results of this study are consistent with the hypothesis that, in the process of evolution, the histologic structures of epiglottis and preepiglottic space likely change to make the larynx descend and lengthen the pharyngeal space of the vocal tract for speech production in humans. Moreover, the distribution of the human preepiglottic space likely allows the epiglottis to more effectively play the role of retroflection during swallowing in order to prevent aspiration.

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.

Objectives There is growing evidence to suggest that the cells in the maculae flavae of the vocal fold mucosa are tissue stem cells of the human vocal fold. This study investigated the metabolic activity of the cells in the maculae flavae of the human vocal fold from the aspect of mitochondrial microstructure. Study design Histologic analysis of the human vocal folds. Methods Five normal human adult vocal folds obtained from autopsy cases were investigated under transmission electron microscopy. Results Mitochondria were randomly distributed in the cytoplasm of the cells. The morphological features of the mitochondria consisted of a double-membrane-bounded body containing matrices and a system of cristae. In each mitochondria, the lamellar cristae were sparse. The intercristal space was occupied by a mitochondrial matrix which contained electron-dense matrix granules, mitochondrial DNA, and ribonucleoprotein granules. Some mitochondria spread out over or fused to the surface of a lipid droplet in the cytoplasm. In addition, both the mitochondrial outer and inner membranes and the membranes of the lipid droplets had disappeared. Some close association between mitochondria and rough endoplasmic reticulum was present. Conclusions The features of the mitochondria of the cells in the maculae flavae of the human vocal fold suggested that their metabolic activity and oxidative phosphorylation were low and that they may have shifted to the utilization of lipids to some extent for their metabolic needs. Level of evidence NA.

Limited information about salvage surgery is available for locally persistent and recurrent maxillary sinus cancers after the completion of chemoradiation therapy. Seventy-six maxillary sinus cancer patients who had undergone chemoradioselection using initial radiotherapy and concomitant intra-arterial cisplatin were screened retrospectively. Twenty-four of these patients who had a locally persistent or recurrent tumour were investigated. The 2-year overall survival rate of patients with maxillary sinus cancer of all types was 39.0% for those who underwent salvage surgery and 10.0% for those who did not. The 2-year overall survival rate of patients with maxillary sinus squamous cell carcinoma was 45.8% for those who underwent salvage surgery and 11.1% for those who did not. Furthermore, the 2-year local control and overall survival rates of patients with positive and negative surgical margins were 14.3% and 83.3% and 14.3% and 66.7%, respectively. There were significant differences in local control (P=0.004) and overall survival (P=0.005) regarding surgical margin status. Although salvage surgery for a locally persistent or recurrent maxillary sinus cancer is a feasible treatment, patients with positive surgical margins are more prone to local relapse. Therefore, surgical safety margins should be assessed thoroughly.

There is growing evidence that the cells in the maculae flavae (MFe) are candidates for tissue stem cells of the vocal fold mucosa and the MFe are a stem cell niche. Distribution of label-retaining cells and their properties in the postnatal vocal fold mucosa were investigated.Oral administration of bromodeoxyuridine (BrdU) was given to pregnant Sprague-Dawley rats and the label-retaining cells in the postnatal vocal fold mucosa were observed by immunohistochemistry. Immunoreactivity to antibodies directed to Ki-67 was studied to investigate the cell cycle.At day 1 after birth, BrdU positive cells were identified in the MFe (60.1 ± 1.7%), epithelium (58.7 ± 10.6%) and lamina propria (52.4 ± 7.8%) of the vocal fold mucosa. At day 56 after birth, the number of BrdU positive cells in the epithelium (4.8 ± 2.2%) and lamina propria (32.3 ± 16.5%) were significantly lower compared to day 1 after birth (P0.05). However, the number of BrdU positive cells remaining in the MFe was still high (56.2 ± 2.5%). The label-retaining cells were distributed throughout the MFe. Few Ki-67 positive cells were identified in the MFe indicating they were resting cells.The results of this study are consistent with the hypothesis that the cells in the postnatal MFe are candidates for tissue stem cells. At birth, these cells are already present in the MFe of the newborn vocal fold and they are likely ready to start the growth and development of the vocal fold mucosa.

OBJECTIVES Limited information exists regarding the associations between pre-existing immune parameters in the tumor immune microenvironment (TIM) and either chemoradiosensitivity or prognosis for patients with squamous cell carcinoma of the nasopharynx or oropharynx involving virus-related or nonvirus-related tumors. STUDY DESIGN Retrospective cohort study. METHODS We retrospectively reviewed 141 patients with EBV+, p16+, or EBV- and p16- statuses who are receiving chemoradiotherapy. We performed immunohistochemistry using pretreatment biopsy specimens to analyze the programed death ligand 1 (PD-L1) levels in tumor and immune cells and CD8+ tumor-infiltrating lymphocyte (TIL) density. We evaluated chemoradiosensitivity and prognosis with respect to these immune-related parameters. RESULTS Virus-related tumors showed associations with both PD-L1 expression and high CD8+ TIL density. Patients with higher CD8+ TIL density or greater numbers of PD-L1+ tumor and immune cells showed significant rates of favorable local recurrence-free survival (LRFS), progression-free survival (PFS), and overall survival (OS). Multivariate analyses demonstrated that higher CD8+ TIL density is an independent, significant, and favorable predictive factor for LRFS (P = .005) and OS (P = .003), although it is not a significant predictor of PFS (P = .077). CONCLUSIONS Higher CD8+ TIL density represents a useful and favorable biomarker of chemoradiosensitivity in patients receiving chemoradiotherapy for nasopharyngeal or oropharyngeal cancer. LEVEL OF EVIDENCE 3 Laryngoscope, 131:E1179-E1189, 2021.

OBJECTIVE Limited information is available regarding the role of programmed death ligand 1 (PD-L1) expression and CD8+ tumor-infiltrating lymphocyte (TIL) density in the tumor immune microenvironment (TIM) of patients with salivary gland carcinoma (SGC). This study aimed to assess the association between the prognosis of SGC patients and the probability of PD-L1 expression in tumor and/or immune cells using the tumor proportion score (TPS), mononuclear immune cell density score (MIDS), combined positive score (CPS), and CD8+ TIL density in the TIM. STUDY DESIGN Retrospective cohort study. METHODS We retrospectively reviewed 73 SGC patients treated with definitive surgery between 2000 and 2015. Immunohistochemical analysis was used to assess TPS, MIDS, CPS, and CD8+ TIL density, followed by prognostic evaluation of these immune-related parameters. RESULTS Histological grade was associated with TPS, MIDS, and CPS based on PD-L1 expression, and these scores exhibited a significant association with CD8+ TIL density. Patients with positive TPS had an unfavorable disease-free survival and overall survival. Multivariate analyses indicated that the TPS was a significant and independent prognostic factor. CONCLUSION Our results suggest that TPS might be a useful prognostic biomarker in SGC patients receiving definitive surgery. Laryngoscope, 131:E1481-E1488, 2021.

BackgroundIn order to improve a large posterior glottal gap and/or aspiration, injections of augmentation substances should not only be administered at the mid-membranous vocal fold in the thyroarytenoid muscle, but also at the cartilaginous portion of the vocal fold to make adduction arytenopexy possible.MethodTen adult human larynges were investigated using the whole-organ serial section technique.ResultsVertical thickness of the posterior aspect of the thyroarytenoid muscle was relatively thin (3.4 ± 0.4 mm), especially in females (3.2 ± 0.3 mm). Consequently, care should be taken to ensure the correct depth of needle placement. If the needle is placed too deep, augmentation substances are injected into the lateral cricoarytenoid muscle, located beneath the thyroarytenoid muscle, or into the paraglottic space, located inferolateral to the thyroarytenoid muscle.ConclusionThe injection location and the amount of injected material should be modified based on the pathological conditions of the voice disorder and aspiration.

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.

Objectives Transendothelial exchange and permeability of the capillaries in Reinke space (the superficial layer of the lamina propria) of the vocal fold mucosa affect physiological and pathological conditions of the human vocal fold mucosa. The mechanism of permeability and Weibel-Palade bodies of the blood vessels in the human vocal fold mucosa were investigated using electron microscopy. Study design Histologic analysis of the human vocal fold. Methods Six normal human vocal folds (three adults and three newborns) obtained from autopsy cases and three human vocal folds with Reinke edema from surgical specimens were investigated under transmission electron microscopy. Results There were three possible capillary wall transport systems related to the permeability of the blood vessels in the vocal fold mucosa: 1) Fenestra transport, plasma exuded from the capillaries into surrounding tissue via the fenestration with or without a diaphragm; 2) vesicular transport (transcellular transport via vesicles), the use of vesicles to ferry fluid and solutes across endothelial cells; and 3) junctional transport (intercellular transport), molecules passed through intercellular gaps between endothelial cells. Weibel-Palade bodies were present in the cytoplasm of endothelial cells both in adults and newborns. They were present in high numbers in the cytoplasm of endothelial cells, with intercellular transport in the vocal folds with Reinke edema. Conclusion There were three types of mechanisms for the permeability of the blood vessels in the human vocal fold mucosa. Some physiologically active substances, such as histamine produced by Weibel-Palade bodies, may adversely influence the permeability of the blood vessels. Level of evidence NA. Laryngoscope, 2588-2592, 2018.

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.

Among tumors of the major salivary glands, tumors in the sublingual gland are rare. Although mucoepidermoid carcinoma (MEC) represents a histological type of salivary gland tumor, it is occasionally difficult to diagnose due to its histological variation. The present study reports a case of MEC harboring a mastermind-like transcriptional coactivator 2 (MAML2) gene translocation in the sublingual gland. A 76-year-old Japanese woman with a mass in the left submandibular region was referred to Kurume University Hospital (Kurume, Japan). Computed tomography scans revealed that the tumor was predominantly located in the sublingual gland, and tumor resection was performed. Histologically, the tumor was composed of cells that exhibited low-grade nuclear atypia and clear and/or granular eosinophilic cytoplasm, and that were proliferating in solid patterns. Periodic acid-Schiff and alcian blue staining revealed a small number of mucinous cells in the tumor. Immunohistochemically, the tumor cells were positive for p40 and p63. Fluorescence in situ hybridization (FISH) analysis revealed a MAML2 gene split. The definitive pathological diagnosis was low-grade MEC, as the case lacked any factors indicative of high-grade malignancy. To the best of our knowledge, this is the first report of MEC in the sublingual gland with MAML2 gene translocation confirmed by FISH.

This study investigates the influence of nationality, ages, and address systems on the use of digital maps in wayfinding. Examining how user—whether they are merely browsing maps or actively trying to find a destination—perceive and interact with their environments. Also, assessing the current problems is regarded digital maps, comparing user experiences of participants from different nationalities, age groups, and genders through a questionnaire. The subjects are Taiwanese and Japanese, and either in their 20s or above the age of 60. The crucial result is focusing on results of determined and undetermined destination how the users operate digital maps. In principal component analysis, age of 20s user have four factors influence digital map functions: (1) Orientation; (2) Advice Tip; (3) Decision Making, and (4) Atmosphere. But for user who are above 60s, they are categorized three factors: (1) Tourism Tip; (2) Orientation; and (3) Surrounding. When 20s go for traveling the orientation will be essential information, nevertheless user who is above 60 sees Tourism Tip as priority.