Neuropathological features of pediatric laryngomalacia.

OBJECTIVE: Laryngomalacia is the most common pediatric laryngeal anomaly. The pathophysiology of laryngomalacia is not well defined; the leading hypothesis suggests weak laryngeal tone and neuromuscular discoordination. Only a few studies explored the histopathology of the laryngeal submucosal nerves, with reported nerve hypertrophy. Our study aims to describe the histopathology of submucosal nerves in specimens obtained from children with severe laryngomalacia compared to pediatric cadaveric controls. STUDY DESIGN: Prospective study. SETTINGS: Tertiary care children's hospital. METHODS: Histologic and immunohistochemical sections of supraglottic tissue from 26 children with severe laryngomalacia and six pediatric autopsies were digitally scanned and assessed with image analysis software (QuPath), resulting in the identification and measurement of 4561 peripheral nerves and over 100,000 foci of neurofilaments. RESULTS: Chronic inflammation was noted in all patients. Eosinophils were rare. The mean nerve area and perimeter were significantly smaller for patients with laryngomalacia compared to the control group (1594.0 ± 593.2 µm^2 vs. 2612.1 ± 2824.0 µm^2, p < 0.0001, and 158.8 ± 30.3 µm vs. 217.6 ± 165.0 µm, p < 0.0001). Nerve-per-area unit was significantly greater for patients with laryngomalacia compared to controls (1.39E-05 vs. 6.19 E-06, p = 0.009). The mean area and the number of neurofilaments per total nerve area were similar. Immunohistochemistry for calretinin, a marker for intestinal ganglion cells in Hirschsprung disease, was absent from all specimens. CONCLUSIONS: This series includes a comparison of all identifiable nerve fibers obtained from children with severe laryngomalacia and shows that the mucosal nerves are smaller on average than controls. These findings fail to provide support for significant morphologic peripheral nerve pathology in laryngomalacia.

Pepsin Inhibitors Prevent Inflammation and Loss of Laryngeal Barrier Function in Mice with Gastroesophageal Reflux.

OBJECTIVE: This study aimed to evaluate the role of pepsin inhibitors in the inflammatory response and their effects on laryngeal mucosal integrity during gastroesophageal reflux (GERD) under in vivo conditions. METHODS: A surgical model of GERD was used, in which mice were treated with pepstatin (0.3 mg/kg) or darunavir (8.6 mg/kg) for 3 days. On the third day after the experimental protocol, the laryngeal samples were collected to assess the severity of inflammation (wet weight and myeloperoxidase activity) and mucosal integrity (transepithelial electrical resistance and paracellular epithelial permeability to fluorescein). RESULTS: The surgical GERD model was reproduced. It showed features of inflammation and loss of barrier function in the laryngeal mucosa. Pepstatin and darunavir administration suppressed laryngeal inflammation and preserved laryngeal mucosal integrity. CONCLUSION: Pepsin inhibition by the administration of pepstatin and darunavir improved inflammation and protected the laryngeal mucosa in a mouse experimental model of GERD. LEVEL OF EVIDENCE: NA Laryngoscope, 134:3080-3085, 2024.

Protection of laryngeal mucosa and function in laryngeal burns by heat absorption of perilaryngeal tissue.

OBJECTIVE: The laryngeal tissue carries most of the heat during inhalation injury. This study aims to explore the heat transfer process and the severity of injury inside laryngeal tissue by horizontally studying the temperature rise process at various anatomical layers of the larynx and observing the thermal damage in various parts of the upper respiratory tract. METHODS: The 12 healthy adult beagles were randomly divided into four groups, and inhaled room temperature air (control group), dry hot air of 80 °C (group I), 160 °C (group II), and 320 °C (group III) for 20 min, respectively. The temperature changes of the glottic mucosal surface, the inner surface of the thyroid cartilage, the external surface of the thyroid cartilage, and subcutaneous tissue were measured every minute. All animals were immediately sacrificed after injury, and pathological changes in various parts of laryngeal tissue were observed and evaluated under a microscope. RESULTS: After inhaling hot air of 80 °C, 160 °C and 320 °C, the increase of laryngeal temperature in each group was ΔT = 3.57 ± 0.25 °C, 7.83 ± 0.15 °C, 11.93 ± 0.21 °C. The tissue temperature was approximately uniformly distributed, and the difference was not statistically significant. The average laryngeal temperature-time curve showed that the laryngeal tissue temperature in group I and group II showed a trend of "first decrease and then increase", except that the temperature of group III directly increased with time. The prominent pathological changes after thermal burns mainly concluded necrosis of epithelial cells, loss of the mucosal layer, atrophy of submucosal glands, vasodilatation, erythrocytes exudation, and degeneration of chondrocytes. Mild degeneration of cartilage and muscle layers was also observed in mild thermal injury. Pathological scores indicated that the pathological severity of laryngeal burns increased significantly with the increase of temperature, and all layers of laryngeal tissue were seriously damaged by 320 °C hot air. CONCLUSIONS: The high efficiency of tissue heat conduction enabled the larynx to quickly transfer heat to the laryngeal periphery, and the heat-bearing capacity of perilaryngeal tissue has a certain degree of protective effect on laryngeal mucosa and function in mild to moderate inhalation injury. The laryngeal temperature distribution was in accordance with the pathological severity, and the pathological changes of laryngeal burns provided a theoretical basis for the early clinical manifestations and treatment of inhalation injury.

The role of Glut-1 and H+/K+-ATPase expression in hyperplasia of mice laryngeal epithelium induced by pepsin.

PURPOSE: To explore the role played by Glut-1 and H+/K+-ATPase in pepsin-induced, mouse laryngeal epithelial proliferation, growth, and development. METHODS: We established a mouse model of laryngopharyngeal reflux and measured Glut-1 and H+/K+-ATPase expression levels in mouse laryngeal epithelium treated with artificial gastric juice containing pepsin. RESULTS: Artificial pepsin-containing gastric juice induced significant hyperplastic changes in mouse laryngeal epithelium compared to control mice at 15, 30, and 45 days. Inhibition of Glut-1 expression by 2-DG significantly suppressed such hyperplasia compared to mice exposed to artificial gastric juice containing pepsin at 15, 30, and 45 days. After treatment with pepsin-containing artificial gastric juice, RT-PCR and Western blotting showed that the levels of Glut-1 and H+/K+-ATPase α, ß increased significantly. CONCLUSIONS: Pepsin-containing artificial gastric juice promoted mouse laryngeal epithelial hyperplasia associated with abnormal expression of Glut-1 and H+/K+-ATPase α, ß.

A Rare Laryngeal Presentation of Stevens-Johnson Syndrome.

Stevens-Johnson syndrome (SJS) is a rare but severe mucocutaneous epidermolysis commonly triggered by medications. SJS is characterized by mucocutaneous lesions of the trunk, face, and limbs, as well as the oral cavity, gastrointestinal tract, and respiratory tract. Although uncommon, laryngeal involvement in SJS can lead to severe respiratory, phonatory and deglutitive complications. Providers caring for patients with SJS should maintain a high index of suspicion for laryngeal involvement and low threshold to solicit Otolaryngology consultation. Laryngeal complications can be more expediently managed when anticipated early in the course of disease. Laryngoscope, 131:2519-2522, 2021.

Mainstream Cigarette Smoke Impacts the Mouse Vocal Fold Epithelium and Mucus Barrier.

OBJECTIVES/HYPOTHESIS: Cigarette smoke (CS) is a primary risk factor for the development of numerous benign and malignant laryngeal diseases. The epithelium and mucus lining the vocal folds (VF) are the first barriers against CS. The primary objective of this study was to investigate epithelial and mucus barrier changes in the mouse laryngeal mucosa upon exposure to subacute CS. The secondary objective was to compare mucus barrier changes in mice and human smokers and nonsmokers. Study Design Animal model. METHODS: Mice were exposed to CS for 4 weeks for 4 hours (N = 12, high dose [HD]) or 1 hour (N = 12, low dose [LD]) per day. Air-exposed mice were used as a control group (N = 10). Larynges were harvested and VF epithelial barrier integrity was evaluated including cellular proliferation and expression of cell junctions. We also investigated mucus production by examining mucus cell area and mucin expression in mice and human smokers and nonsmokers. RESULTS: HD CS increased VF epithelial cellular proliferation but did not alter the expression of cell junctions. HD CS also induced hypertrophy of the mucus-producing submucosal glands. However, only LD CS increased MUC5AC gene expression. MUC5AC staining appeared elevated in laryngeal specimens from smokers, but this was not significant as compared to nonsmokers. CONCLUSIONS: These findings help us identify potential adaptive mechanisms to CS exposure as well as set the foundation for further study of key aspects of epithelial and mucus barrier integrity that may be implicated in laryngeal disease development following prolonged smoking. LEVEL OF EVIDENCE: NA Laryngoscope, 131:2530-2539, 2021.

Laryngotracheal Mucosal Surface Expression of Candidate Biomarkers in Idiopathic Subglottic Stenosis.

OBJECTIVES: Idiopathic subglottic stenosis (iSGS) is an inflammatory process leading to fibrosis and narrowing of the laryngotracheal airway. There is variability in patient response to surgical intervention, but the mechanisms underlying this variability are unknown. In this pilot study, we measure expression of candidate targets at the mucosal surface of the subglottis in iSGS patients. We aim to identify putative biomarkers for iSGS that provide insights into the molecular basis of disease progression, yield a gene signature for the disease, and/or predict a response to therapy. STUDY DESIGN: In vitro comparative study of human cells. METHODS: Levels of candidate transcripts and proteins were measured in healthy and stenotic laryngotracheal tissue specimens taken from the mucosal surface in 16 iSGS patients undergoing endoscopic balloon dilation. Pre- and post-operative pulmonary function test and patient reported voice and breathing outcomes were also assessed. Unsupervised clustering was used to define patient subgroups based on expression profile. RESULTS: Pulmonary function and voice and breathing outcome metrics demonstrated significant post-operative improvement. Transcript levels of αSMA, CCL2, COL1A1, COL3A1, FN1, IFNG, and TGFB1 and protein levels of CCL2, IFNG, and IL-6 were significantly upregulated in stenotic as compared to healthy tissues. Marked heterogeneity was observed in the patterns of expression of candidate markers across individuals and tissue types. Patient subgroups defined by expression profile did not show a statistically significant difference in dilation interval. CONCLUSION: Pro-inflammatory and pro-fibrotic pathways are significantly upregulated along the mucosal surface of stenotic laryngotracheal tissues, and CCL2 and IFNG merit further investigation as potential iSGS biomarkers. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:342-349, 2021.

Laryngeal Mucosa Alterations in Mice Model of Gastroesophageal Reflux: Effects of Topical Protection.

OBJECTIVES/HYPOTHESIS: The objectives of this study were to evaluate laryngeal inflammation and mucosal integrity in a murine model of reflux disease and to assess the protective effects of topical agents including alginate, hyaluronic acid, and cashew gum. STUDY DESIGN: Animal study. METHODS: A surgical murine model of reflux disease was evaluated at 3 or 7 days postsurgery, and laryngeal samples were collected to measure inflammation (wet weight and myeloperoxidase [MPO]) and mucosal integrity (transepithelial resistance [TER] and mucosal permeability to fluorescein). Additional groups of animals were administered one of several topical agents (alginate, hyaluronic acid, or cashew gum) daily, and laryngeal inflammation and mucosal integrity were evaluated at 3 days postsurgery. RESULTS: At 3 days, and not 7 days postsurgery, we observed increased laryngeal wet weight and MPO, decreased laryngeal TER, and increased laryngeal mucosa permeability. Alginate partially decreased laryngeal inflammation (wet weight and not MPO) and dramatically improved laryngeal mucosal integrity. Conversely, hyaluronic acid eliminated the inflammation; however, it had no effect on laryngeal mucosal integrity impairment. Cashew gum eliminated laryngeal inflammation as well as the impairment in laryngeal mucosal integrity. CONCLUSIONS: This study shows that a surgical model of reflux disease induced laryngeal inflammation and impairment in laryngeal barrier function. These observed alterations were partially attenuated by alginate and hyaluronic acid and completely reversed by cashew gum. LEVEL OF EVIDENCE: NA Laryngoscope, 2020.

Persistent sore throat: a case of laryngeal mucous membrane pemphigoid.

We present a case of a 72-year-old women who presented with a persistent sore throat and productive cough. On flexible nasendoscopy examination, she was found to have a fairly superficial ulcer affecting the laryngeal surface and tip of her epiglottis. On her second microlaryngoscopy and biopsy, direct immunofluorescent staining of the biopsy was analysed and the histological findings were in keeping with a diagnosis of mucous membrane pemphigoid (MMP). MMP is a rare chronic autoimmune condition characterised by the presence of blistering subepithelial lesions that can cause scarring. Laryngeal MMP affects only 1 in 10 million people and can lead to life-threatening airway compromise arising from scarring and stenosis. As there is a large spectrum of disease, it is important to adopt a multidisciplinary approach including dermatologists, otolaryngologists and ophthalmologists for prompt diagnosis and early recognition of potential complications, maximising functional outcomes for patients.

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.

LncRNA SNHG20 promotes the development of laryngeal squamous cell carcinoma by regulating miR-140.

OBJECTIVE: This study aims to investigate the expression level of long non-coding RNA (lncRNA) SNHG20 in laryngeal squamous cell carcinoma (LSCC), and to explore further whether it can promote the development of LSCC by regulating microRNA-140 (miR-140). PATIENTS AND METHODS: Expression levels of SNHG20 in 56 pairs of LSCC tissues and adjacent normal tissues were measured by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). The relationship between SNHG20 expression with pathological parameters and the prognosis of LSCC was analyzed. Besides, the SNHG20 expression in LSCC cells was also analyzed by qRT-PCR. The SNHG20 knockdown and overexpression model were constructed by lentivirus transfection in AMC-HN-8 and Hep-2 cells. Cell counting kit-8 (CCK-8) and 5-Ethynyl-2'-deoxyuridine (EdU) assay were used to analyze the effect of SNHG20 on the biological function of LSCC cells. Finally, the dual-luciferase reporter gene assay was performed to explore the potentials of SNHG20 and miR-140 in LSCC. RESULTS: The SNHG20 expression in LSCC tissues or cells remarkably increased than controls, and the difference was statistically significant. The LSCC patients with the high expression level of SNHG20 were more likely to develop advanced tumor compared with patients with low expression of SNHG20. Moreover, the LSCC patients with the high expression level of SNHG20 had a shorter overall survival than those with low level. The cell proliferation ability significantly decreased in the SNHG20 knockdown group, while notably increased in SNHG20 overexpression group. MiR-140 was negatively correlated with SNHG20 in LSCC tissues and cells. Dual-luciferase reporter gene assay showed that SNHG20 could be targeted by miR-140 through a certain binding site. The cell rescue experiment also indicated that there was a mutual regulation between SNHG20 and miR-140, which could together affect the malignant progression of LSCC. CONCLUSIONS: We showed that the expression levels of SNHG20 in LSCC tissues or cell lines significantly increased and was associated with advanced tumor staging and undesirable prognosis of LSCC. In addition, SNHG20 could promote the malignant progression of LSCC.

Two-handed tying technique in vocal fold mucosa microsuture for the treatment of Reinke's edema.

BACKGROUND: Removal of Reinke's edema may result in moderate to large-sized mucosal defect on the vocal fold, which heals by secondary intention. Microsuturing this defect may lead to primary wound healing with fastened recovery and less scar, but costs extra time and effort. Exploring methods that can shorten microsuture time is helpful for the wider application of this technology. STUDY DESIGN: Retrospective. METHODS: 57 patients with Reinke's edema, who were admitted from November 2010 to June 2018, were enrolled as research subjects for the retrospective analysis. 27 patients were the knot pusher group (from November 2010 to March 2015), and 30 patients were the two-handed tying group (from April 2015 to June 2018). Evaluation indicators include the number of knots, the average time for suturing and tying the knot for each patient, and the occurrence of complications, subjective and objective voice assessments. RESULTS: All patients underwent successful operation. The average time for making knots in the knot pusher group and two-handed tying group was 668.40 ± 173.73 s and 328.73 ± 121.0 s, respectively, and there was a statistically significant difference between the two groups (p < 0.001). No significant difference was noted in the mucosal avulsion, overall incidence of complications between the groups, and no significant difference was found between the two groups in terms of the preoperative and 3-month postoperative subjective and objective indicators. CONCLUSION: Microsuturing of Reinke's edema microflaps using the two-handed tying technique can achieve the similar effect with the knot pusher method, and save operation time while the surgeon is well trained. LEVEL OF EVIDENCE: 4.

Diagnosis of laryngopharyngeal reflux in children with voice disorders using 24-hour pharyngeal pH monitoring.

OBJECTIVES: The aim of this study was to assess the usefulness of 24-h pharyngeal pH monitoring in the diagnosis of laryngopharyngeal reflux (LPR) in children with voice disorders. METHODS: The study was conducted on 68 children aged 3-18 years old. In all cases, pH monitoring was successful; no child removed the probe from the nasal cavity or reported discomfort or other complaints. The following definitions were adopted: LPR in the upright position if Ryan Score upright >9.41; LPR in the supine position if there was at least one supine episode below pH 5.0 (equal to a Ryan Score supine >2.91). RESULTS: In 43 children (63%), vocal fold edema was strongly related to recorded reflux episodes, especially in the upright position. In 18 children (26%), vocal nodules were observed, but their occurrence did not significantly affect the Ryan Score, either upright or supine. The selected potential LPR markers were significantly correlated to all the pH monitoring variables and individual elements on the Reflux Symptoms Index and the Reflux Finding Score questionnaire. CONCLUSION: Our findings indicate that, together with vocal fold edema, laryngeal edema and posterior commissure mucosal hypertrophy are important determinants of paediatric LPR. In fact, if LPR is suspected in a child, 24-h pharyngeal pH monitoring appears to be a valuable and welltolerated diagnostic tool. Vocal fold edema observed in laryngeal endoscopy can be considered a probable sign of LPR. The Reflux Finding Score appears to be helpful in diagnosing LPR in children, especially if a cut-off value of 4/5 is adopted.

Effect of Electronic Cigarettes on the Inner Mucosa of the Craniofacial Region.

OBJECTIVES: The aim of this paper is to investigate electronic cigarettes (e-cigarettes) from the otorhinolaryngologic point of view. METHODS: The authors searched Central Database of Kirikkale University Library, Google, PubMed, and Proquest and Google Scholar. RESULTS: An electronic cigarette or e-cigarette is a battery-powered device that vaporizes a liquid, generally including nicotine. Nowadays, e-cigarettes are used for smoking cessation or to reduce the consumption of conventional tobacco cigarettes. First generation e-cigarette devices were similar to conventional tobacco cigarettes in terms of shape and size and expressed as "cigalikes." Differently from traditional cigarettes in which tobacco is burned to generate smoke, electronic cigarettes contain a tank filled with liquid. It was found that e-cigarette liquids contained different types of chemical compounds which were either previously known carcinogens or probably prove to be carcinogenic to humans in the near future. It seems that the use of electronic cigarette does not harm the oral cells. However, the use of e-cigarette for 4 weeks led to metaplasia and hyperplasia of the laryngeal mucosa in rats. Furthermore, e-ciagarettes produce some adverse effects on the nasal mucosa, supressing the immune system. CONCLUSION: It should not be considered that e-cigarettes are safer unless their effects on the mucosa of the ear, nose, and throat are more precisely clarified.

Pediatric dysphagia: Is interarytenoid mucosal height significant?

OBJECTIVES: The clinical significance of the interarytenoid mucosal height (IAMH) in pediatric dysphagia, ranging from normal anatomy to a laryngeal cleft, is unknown. This study seeks to evaluate a cohort of patients who underwent evaluation of their IAMH during microdirect laryngoscopy (MDL) for associations between IAMH and dysphagia as diagnosed on preoperative videofluoroscopic swallow study (VFSS). METHODS: A retrospective case series of 1,351 patients who underwent MDL between 2011 and 2016 were reviewed for intraoperative evaluation of IAMH using our interarytenoid assessment protocol. After exclusions, 182 patients were divided into three groups: 1) thickened diet: VFSS with recommendation for thickened liquids (n = 82 of 182; 45.1%), 2) normal diet: VFSS with allowance of thin liquids (n = 19 of 182; 10.4%), and 3) control: no VFSS performed (n = 81 of 182; 44.5%). RESULTS: There was no difference in IAMH between groups (P = 0.35). Power analysis was able to achieve > 80% power to detect an effect size of ≥ 0.5 (1-5 mucosal height scale). The majority of patients in each group had an IAMH above the false vocal folds (thickened diet: 57.3%, normal diet: 57.9%, control: 64.2%). There were similar percentages of patients in each group with an IAMH at or below the true vocal folds (thickened diet: 4.9%, normal diet: 5.3%, control: 6.1%). CONCLUSION: There was no significant association between IAMH and preoperative thickened liquid recommendation in this cohort. This data fails to support the hypothesis that the IAMH is an independent etiological factor for pediatric pharyngeal dysphagia. Further studies comparing IAMH with outcomes after feeding therapy and surgery may better clarify this relationship between anatomy and physiology. LEVEL OF EVIDENCE: 4. Laryngoscope, 129:2588-2593, 2019.

Improved Mucosal Wave in Unilateral Autologous Temporal Fascia Graft in Sulcus Vocalis Type 2 and Vocal Scars.

OBJECTIVES/HYPOTHESIS: We analyzed the results of 10 patients treated by unilateral autologous temporal fascia graft, comparing the pre and post surgery results, as well as the appearance of the wave and the intervals until the re-appearance of it. STUDY DESIGN: Retrospective, clinical case series. METHODS: Subjective and objective evaluation was preoperatively and postoperatively performed, using laryngovideostroboscopy, the Voice Handicap Index-10, GRBAS (grade, roughness, breathiness, asthenia, and strain), harmonics to noise ratio, Jitter, Shimmer, phonatory range, maximum phonation time, and S/Z ratio in all patients. Postoperative visits were scheduled after 1 week, 1 month, at 3 months, and at 6 months after the surgery. RESULTS: After surgery, we found significant differences in the maximum phonation time and the S/Z ratio (P <0.05). Most parameters of GRBAS also improved significantly, both in general and in the subscales, except for Breathiness and Asthenia (P <0.05). There was an average decrease in Voice Handicap Index-10 of 11.2 (P <0.05). At laryngovideostroboscopy, the mucous wave reappeared in all patients treated 1 month after surgery, and increased in amplitude until 6 months postoperative.

Probe-based confocal laser endomicroscopy for diagnosis of nasopharyngeal carcinoma in vivo.

OBJECTIVES/HYPOTHESIS: Probe-based confocal laser endomicroscopy (pCLE) is a novel technique allowing real-time evaluation of the histological features of tissues in vivo at the cellular level. This study aimed to evaluate the feasibility of using pCLE in the diagnosis of nasopharyngeal carcinoma (NPC). STUDY DESIGN: Feasibility study. METHODS: In this study, the pCLE images of the lesions, as well as the surrounding or contralateral normal mucosa of the lesions, were acquired in vivo from each patient after intravenous injecting of 2.5 mL fluorescein. Biopsy specimens were collected at the imaged sites followed by a histopathological diagnosis by the pathologists, which was used as the gold standard. The pCLE images were compared to histopathological diagnosis of visualized sites by using sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV). RESULTS: Diagnoses based on pCLE images correlated well with the gold standard diagnoses based on tissue histology. The overall sensitivity, specificity, PPV, and NPV for diagnosis of carcinoma versus nondysplasia were 93.8% (67.7%-99.7%), 90.5% (68.2%-98.3%), 88.2% (62.3%-97.9%), and 95.0% (73.1%-99.7%), respectively, and the four indices for pCLE diagnosis of dysplasia versus nondysplasia were 60.0% (17.0%-92.7%), 80.9% (57.4%-93.7%), 42.9% (11.8%-79.8%), and 89.5% (65.5%-98.2%), respectively. The overall sensitivity for diagnosis of carcinoma versus dysplasia was 93.8% (67.7%-99.7%), specificity was 40% (7.3%-83.0%), PPV was 83.3% (57.7%-95.6%), and the NPV was 66.7% (12.5%-98.2%). CONCLUSIONS: CLE is a suitable and valid method for otolaryngologists to diagnose of NPC in vivo. LEVEL OF EVIDENCE: NA Laryngoscope, 129:897-902, 2019.

Structural biology of intraepithelial neuroendocrine cells in the larynx: Literature review.

Current knowledge of laryngeal neuroendocrine cells in man and other vertebrates is reviewed. Particular attention is paid to differences in the distribution of neuroendocrine cells between squamous and respiratory laryngeal mucosa, foetal versus post-natal spatial arrangements, relation to the laryngeal cavity and nerve fibres, and immunoreactivities of these cells. Methodological deficiencies and gaps in knowledge are outlined. Comparisons with neuroendocrine cells in lung and gut are drawn, caution with regard to existing histogenetic models of laryngeal neuroendocrine neoplasia is advised and lines of future research are suggested.

Shar Pei Larynx: Supraglottic and Postcricoid Mucosal Redundancy and Its Association With Medical Comorbidities.

OBJECTIVES:: The aim of this study is to describe a clinical entity the authors term "Shar Pei larynx," characterized by redundant supraglottic and postcricoid mucosa that the authors hypothesize coexists in patients with obstructive sleep apnea, laryngopharyngeal reflux, and obesity. By exploring this hypothesis, the authors hope to set the foundation for future research with the goal of identifying whether Shar Pei larynx is a marker for untreated sleep apnea or other diseases. STUDY DESIGN:: Retrospective chart review. SETTING:: Two tertiary care academic institutions. METHODS:: Data were collected from a 5-year period by querying for patients described to have "Shar Pei larynx" or "posterior supraglottic and/or postcricoid mucosal redundancy" on laryngoscopic findings. Relevant demographic and clinical characteristics were analyzed, with a focus on associations with obesity, sleep apnea, and laryngopharyngeal reflux. RESULTS:: Thirty-two patients were identified with physical findings consistent with Shar Pei larynx. Twenty-six patients (81.3%) were obese; 16 (50%) were morbidly obese. Twenty-two patients (68.8%) either had an existing diagnosis of obstructive sleep apnea or were diagnosed on polysomnography performed after initial evaluation. Sixteen patients (50%) had type 2 diabetes mellitus, and 87.5% of these patients were obese. Twenty-eight patients (87.5%) noted histories of reflux, with a median reflux symptom index of 27 of 45. Five patients underwent procedures to reduce mucosal redundancy related to Shar Pei larynx. CONCLUSIONS:: This pilot study confirms that the majority of patients diagnosed with Shar Pei larynx also had diagnoses of obesity, obstructive sleep apnea, and reflux disease. The demonstrated association is strong enough to warrant further study.