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The Laryngoscope Feb 2021Idiopathic subglottic stenosis (iSGS) is an inflammatory process leading to fibrosis and narrowing of the laryngotracheal airway. There is variability in patient...
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.
Topics: Adult; Aged; Biomarkers; Dilatation; Disease Progression; Endoscopy; Female; Fibrosis; Humans; Laryngeal Mucosa; Laryngostenosis; Larynx; Male; Membrane Proteins; Middle Aged; Pilot Projects; Predictive Value of Tests; Respiratory Function Tests; Trachea; Transcriptome
PubMed: 32369195
DOI: 10.1002/lary.28712 -
European Archives of... Oct 2019Laryngeal neoplasms are almost always epithelial in origin and squamous cell carcinoma is the most common tumor of the larynx. Non-epithelial tumors make a small subset...
PURPOSE
Laryngeal neoplasms are almost always epithelial in origin and squamous cell carcinoma is the most common tumor of the larynx. Non-epithelial tumors make a small subset of laryngeal neoplasms. We present the experience of a single institution to define clinical presentations and outcomes.
MATERIALS AND METHODS
The pathology archives and clinical records of our center with the diagnosis of laryngeal tumors between the 2005 and 2018 were reviewed. Age, gender, symptoms, location of the tumor, histopathological diagnosis, treatment modality and disease status were discussed.
RESULTS
657 patients were diagnosed with laryngeal tumor between 2005 and 2018 and 13 patients with non-epithelial tumors were identified. The majority of the patients were male. The age ranged between 13 and 93 years. The most common tumor localizations were vocal cords and subglottis. Seven patients were diagnosed with malignant tumors and six patients had benign tumors. Chondrosarcoma was the most common malignant mesenchymal tumor. Others were leiomyosarcoma, fibrosarcoma and liposarcoma. The most common benign non-epithelial tumors were schwannoma and hemangioma. Plexiform neurofibroma and granular cell tumor were the other benign tumors. Eleven patients underwent excisional biopsy. One patient underwent partial laryngectomy and one had total laryngectomy. Three cases presented with recurrent tumor. Among the recurrent cases, two were malignant tumors.
CONCLUSION
Non-epithelial tumors of the larynx are rare and have a wide histological diversity. Immunohistochemical studies are of great importance in the diagnosis of these tumors. Primary mesenchymal tumors of the larynx should be kept in mind in differential diagnosis.
Topics: Aged; Biopsy; Chondrosarcoma; Female; Humans; Laryngeal Neoplasms; Laryngectomy; Liposarcoma; Male; Middle Aged; Neoplasm Recurrence, Local; Neurilemmoma; Outcome Assessment, Health Care; Retrospective Studies; Turkey; Vocal Cords
PubMed: 31256243
DOI: 10.1007/s00405-019-05527-0 -
The Laryngoscope Jul 2021Iatrogenic laryngotracheal stenosis (iLTS) is the pathological narrowing of the glottis, subglottis, and/or trachea due to scar tissue. Patients with type 2 diabetes...
OBJECTIVES
Iatrogenic laryngotracheal stenosis (iLTS) is the pathological narrowing of the glottis, subglottis, and/or trachea due to scar tissue. Patients with type 2 diabetes mellitus (T2DM) are over 8 times more likely to develop iLTS and represent 26% to 53% of all iLTS patients. In this investigation, we compared iLTS scar-derived fibroblasts in patients with and without T2DM.
STUDY DESIGN
Controlled ex vivo study.
METHODS
iLTS scar fibroblasts were isolated and cultured from subglottic scar biopsies in iLTS patients diagnosed with or without type 2 diabetes (non-T2DM). Fibroblast proliferation, fibrosis-related gene expression, and metabolic utilization of oxidative phosphorylation (OXPHOS) and glycolysis were assessed. Contractility was measured using a collagen-based assay. Metabolically targeted drugs (metformin, phenformin, amobarbital) were tested, and changes in fibrosis-related gene expression, collagen protein, and contractility were evaluated.
RESULTS
Compared to non-T2DM, T2DM iLTS scar fibroblasts had increased α-smooth muscle actin (αSMA) expression (8.2× increased, P = .020), increased contractility (mean 71.4 ± 4.3% vs. 51.7 ± 16% Δ area × 90 minute , P = .016), and reduced proliferation (1.9× reduction at 5 days, P < .01). Collagen 1 (COL1) protein was significantly higher in the T2DM group (mean 2.06 ± 0.19 vs. 0.74 ±.44 COL1/total protein [pg/μg], P = .036). T2DM iLTS scar fibroblasts had increased measures of OXPHOS, including basal respiration (mean 86.7 vs. 31.5 pmol/minute/10 μg protein, P = .016) and adenosine triphosphate (ATP) generation (mean 97.5 vs. 25.7 pmol/minute/10 μg protein, P = .047) compared to non-T2DM fibroblasts. Amobarbital reduced cellular contractility; decreased collagen protein; and decreased expression of αSMA, COL1, and fibronectin. Metformin and phenformin did not significantly affect fibrosis-related gene expression.
CONCLUSION
T2DM iLTS scar fibroblasts demonstrate a myofibroblast phenotype and greater contractility compared to non-T2DM. Their bioenergetic preference for OXPHOS drives their increased contractility, which is selectively targeted by amobarbital.
LEVEL OF EVIDENCE
NA Laryngoscope, 131:1570-1577, 2021.
Topics: Adult; Aged; Amobarbital; Biopsy; Case-Control Studies; Cell Proliferation; Cells, Cultured; Cicatrix; Constriction, Pathologic; Diabetes Mellitus, Type 2; Energy Metabolism; Female; Glottis; Glycolysis; Humans; Hypoglycemic Agents; Iatrogenic Disease; Intubation, Intratracheal; Laryngostenosis; Male; Metformin; Middle Aged; Muscle Contraction; Myofibroblasts; Oxidative Phosphorylation; Phenformin; Primary Cell Culture; Trachea; Tracheal Stenosis; Tracheostomy; Young Adult
PubMed: 32857885
DOI: 10.1002/lary.29026 -
The Laryngoscope Sep 2020Idiopathic progressive subglottic stenosis (IPSS) predominantly affects females in perimenopause. It has, therefore, been hypothesized that estrogen is involved in its...
BACKGROUND/OBJECTIVES
Idiopathic progressive subglottic stenosis (IPSS) predominantly affects females in perimenopause. It has, therefore, been hypothesized that estrogen is involved in its pathogenesis. There are two main types of estrogen receptors: ER-α and ER-β. Abnormal variants of ER-β have previously been shown to be associated with poor wound healing. Estrogen receptors have recently been identified in subglottic tissue samples, with elevated levels of ER-α and progesterone receptors, and no expression of ER-β, in stenotic specimens reported in one study. The objective of this study was to confirm the presence of estrogen receptors in the subglottis and investigate levels of expression and types of estrogen receptors in normal and stenotic subglottic tissue.
METHODS
Subglottic tissue was obtained from three female and one male cadaver without laryngotracheal pathology to serve as controls. Subglottic tissue specimens from five female patients with IPSS were also analysed. Immunofluorescence stains for ER-α and ER-β were performed on specimens. Staining patterns were compared qualitatively and semi-qualitatively between control and IPSS specimens.
RESULTS
Immunofluorescence stains demonstrated the presence of both ER-α and ER-β in subglottic tissue. IPSS specimens demonstrated significantly greater staining intensity of ER-α in the epithelium and ER-β in glands and ducts compared to controls.
CONCLUSIONS
This study confirms the presence of estrogen receptors in the subglottis. Increased expression of ER-α in the epithelium and ER-β in glands and ducts in IPSS compared to controls may help to explain the predisposition to stenosis in these individuals.
LEVEL OF EVIDENCE
3b Laryngoscope, 130:2186-2191, 2020.
Topics: Adult; Aged; Cadaver; Case-Control Studies; Estrogen Receptor alpha; Estrogen Receptor beta; Female; Fluorescent Antibody Technique; Humans; Laryngostenosis; Larynx; Male; Middle Aged; Sex Factors; Trachea; Tracheal Stenosis
PubMed: 31643093
DOI: 10.1002/lary.28364 -
Archivos Argentinos de Pediatria Jun 2022The larynx is at the aerodigestive crossroads; any pathology that involves it will have an impact on breathing, swallowing and/or the voice. It`s divided into three...
The larynx is at the aerodigestive crossroads; any pathology that involves it will have an impact on breathing, swallowing and/or the voice. It`s divided into three regions: supraglottis (includes epiglottis, ventricular bands and laryngeal ventricles), glottis (space limited by the vocal cords) and subglottis (narrowest area of pediatric airway and the only point of larynx completely surrounded by cartilage: the cricoid ring). Laryngeal obstruction can present as a potentially fatal acute condition or as a chronic process. The main symptom is inspiratory or biphasic stridor. The etiology varies widely according to age and it may be of congenital, inflammatory, infectious, traumatic, neoplastic or iatrogenic origin. We describe the pathologies that cause laryngeal obstruction, either those that occur very often or those which are important for their severity, their guiding symptoms to the presumptive diagnosis, additional studies and treatment.
Topics: Airway Obstruction; Algorithms; Child; Humans; Laryngeal Diseases; Larynx; Pediatrics
PubMed: 35533130
DOI: 10.5546/aap.2022.209 -
Toxicology Reports 2021The larynx is an essential organ in the respiratory tract and necessary for airway protection, respiration, and phonation. Cigarette smoking is a significant risk factor...
The larynx is an essential organ in the respiratory tract and necessary for airway protection, respiration, and phonation. Cigarette smoking is a significant risk factor associated with benign and malignant laryngeal diseases. Despite this association, the underlying mechanisms by which cigarette smoke (CS) drives disease development are not well elucidated. In the current study, we developed a short-term murine whole body inhalation model to evaluate the first CS-induced cellular responses in the glottic [i.e. vocal fold (VF)] and subglottic regions of the larynx. Specifically, we investigated epithelial cell proliferation, cell death, surface topography, and mucus production, at various time points (1 day, 5 days, 10 days) after ∼ 2 h exposure to 3R4F cigarettes (Delivered dose: 5.6968 mg/kg per cigarette) and following cessation for 5 days after a 5 day CS exposure (CSE). CSE elevated levels of BrdU labeled proliferative cells and p63 labeled epithelial basal cells on day 1 in the VF. CSE increased proliferative cells in the subglottis at days 5, 10 and following cessation in the subglottis. Cleaved caspase-3 apoptotic activity was absent in VF at all time points and increased at day 1 in the subglottis. Evaluation of the VF surface by scanning electron microscopy (SEM) revealed significant epithelial microprojection damage at day 10 and early signs of necrosis at days 5 and 10 post-CSE. SEM visualizations additionally indicated the presence of deformed cilia at days 5 and 10 after CSE and post-cessation in the respiratory epithelium lined subglottis. In terms of mucin content, the impact of short-term CSE was observed only at day 10, with decreasing acidic mucin levels and increasing neutral mucin levels. Overall, these findings reveal regional differences in murine laryngeal cellular responses following short-term CSE and provide insight into potential mechanisms underlying CS-induced laryngeal disease development.
PubMed: 33996505
DOI: 10.1016/j.toxrep.2021.04.007 -
Oral Surgery, Oral Medicine, Oral... Jul 2020The purpose of this study was to evaluate the patterns of care and survival in the nonsurgical management of early-stage (T1/2 N0 M0) laryngeal cancer.
BACKGROUND
The purpose of this study was to evaluate the patterns of care and survival in the nonsurgical management of early-stage (T1/2 N0 M0) laryngeal cancer.
STUDY DESIGN
This was a retrospective cohort study using data from the Surveillance, Epidemiology, and End Results (SEER) database during the period 2004 to 2015. Patients diagnosed with T1/2 N0 M0 laryngeal SCC definitively treated without surgery were included. Study predictors were age, gender, race, marital status, histologic grade, stage, and management strategy defined as radiotherapy (RT), chemotherapy, chemoradiotherapy (CRT), or no treatment. Study outcomes were overall survival (OS) and disease-specific survival (DSS).
RESULTS
In total, 3221 patients comprised the final sample. Over half of the lesions were stage I (63.8%); 74.0%, 24.8%, and 1.2% were located in the glottis, supraglottis, and subglottis, respectively. RT (77.6%) was the preferred nonsurgical treatment modality, followed by CRT (12.7%). A greater proportion of patients with stage II disease (25.1%) received CRT compared with those with stage I (5.6%). Similarly, patients receiving CRT were significantly younger and more likely to present with higher-grade lesions located in the supraglottis and subglottis. In the multivariate model, the risks of both disease-specific and overall death were increased by age, male gender, supraglottic and subglottic location, stage II disease, CRT, and no treatment.
CONCLUSIONS
Definitive RT was the preferred treatment modality regardless of tumor characteristics. CRT was more often selectively reserved for younger patients with higher grade, stage II tumors located in the supraglottis and subglottis. This approach may be driven by the poorer rates of survival associated with these particular characteristics. CRT did not appear to improve survival in comparison with RT after controlling for subsite and disease severity; however, future clinical studies are required to validate this finding.
Topics: Carcinoma, Squamous Cell; Chemoradiotherapy; Glottis; Humans; Laryngeal Neoplasms; Male; Neoplasm Staging; Retrospective Studies; Survival Rate
PubMed: 32487468
DOI: 10.1016/j.oooo.2020.01.006 -
Zhonghua Er Bi Yan Hou Tou Jing Wai Ke... Aug 2023To analyze the clinical features, diagnosis, treatment and prognosis of nodular fasciitis (NF) in the head and neck. Seven cases of primary NF in the head and neck...
To analyze the clinical features, diagnosis, treatment and prognosis of nodular fasciitis (NF) in the head and neck. Seven cases of primary NF in the head and neck admitted to Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology from 1990 to 2022 were retrospectively analyzed, including 3 males and 4 females, aged from 2 to 67 years, and the location, course of disease, clinical manifestations, imaging findings, and treatment results of the disease were summarized. Of the 7 patients, the primary sites were respectively nasal vestibule, paranasal sinus, nasal dorsum, sella turcica and clivus, neck, subglottis, and tonsil. Three cases presented with rapidly growing subcutaneous painless masses within 2 months, 1 case presented with hemoptysis, hoarseness and asthma for 28 days, 1 case presented with blood in the nasal discharge for 2 months, 1 case presented with headache for 1 month, and 1 case was found to have tonsillar neoplasms on physical examination for 3 days. CT was performed in 5 patients and the lesions showed soft tissue density shadows, and MRI was also performed in 2 of them, which showed T1 isointensity or T2 slightly long abnormal signal shadows. All patients underwent simple surgical resection of the mass. The patients were followed up for 13 months to 10 years, and none had recurrence. Primary NF in the head and neck is rare, with atypical clinical symptoms and imaging findings. Surgery is the mainstay of treatment for NF with good results.
Topics: Female; Male; Humans; Retrospective Studies; Head; Neck; Asthma; Fasciitis
PubMed: 37599239
DOI: 10.3760/cma.j.cn115330-20221228-00775 -
Ear, Nose, & Throat Journal Sep 2022Perioperative risk stratification of pediatric patients undergoing airway intervention remains crucial in identifying those at a higher risk of requiring postoperative...
OBJECTIVE
Perioperative risk stratification of pediatric patients undergoing airway intervention remains crucial in identifying those at a higher risk of requiring postoperative intensive care unit (ICU) care. Here we determined the likelihood of and possible risk factors for developing perioperative adverse respiratory events (PAREs) requiring ICU care after various pediatric endoscopic airway surgeries (EASs).
METHODS
We conducted a retrospective chart review of pediatric patients who were aged <18 years and underwent EAS between 2015 and 2021. Early postoperative adverse events within 24 h of surgery were recorded and analyzed.
RESULTS
Overall, 99 patients who underwent EAS were included. The age at the time of the intervention ranged from 8 months to 18 years. Fifty-eight patients, median age was 4.83 years, underwent papilloma debulking with no high likelihood of PARE in this patient subgroup (OR = 0.48; 0.16-1.44). Twenty-five patients, median age was 9.72 years, underwent balloon dilation of laryngotracheal stenosis with no increase in the likelihood of PARE in this patient population (OR = 2.02; 0.65-6.28). Early postoperative respiratory events occurred in 16 patients (16.2%). Most of these events (75%) manifested within 4 h after surgery. In a univariate analysis, intervention at the level of the subglottis or 2 or more laryngeal subsites increased the risk of PARE (OR = 6.57; 1.11-12.52 and OR = 3.73; 1.93-22.34, respectively). In a multivariate analysis, only intervention in the subglottic area maintained its effect (OR = 6.84; 1.82-25.65).
CONCLUSION
Respiratory adverse events following pediatric EAS are not uncommon, and the majority are encountered shortly after surgery. Intervention in the subglottic area was an independent predictor of PARE.
PubMed: 36112766
DOI: 10.1177/01455613221128111 -
Indian Journal of Otolaryngology and... Jun 2023The main purpose of this study is to evaluate and understand the clinical profile of patients presenting to an Indian tertiary care referral centre with Laryngotracheal...
The main purpose of this study is to evaluate and understand the clinical profile of patients presenting to an Indian tertiary care referral centre with Laryngotracheal Stenosis (LTS) and also to emphasise on the outcomes after treatment in these patients. This is a prospective observational study conducted at a tertiary care referral centre which included 18 patients diagnosed with LTS. All patients were evaluated clinically and radiologically to evaluate the degree of stenosis, site and length of the stenotic segment involved, intervened surgical procedure, intraoperative and postoperative complications following the procedure were all documented and taken into consideration. The data collected was analysed. The most common etiological cause of LTS was post intubation (77.8%). 61.5% among the 13 intubated patients had a history of intubation for more than 10 days. 83.3% of the cases had stenosis at the level of the subglottis and cervical trachea level. Post intubational airway stenosis is the most common cause of LTS. A precise assessment of the laryngotracheal complex is the cornerstone of LTS management. The choice of treatment depends on the location, severity, and length of stenosis, as well as on the patient's comorbidities, history of previous interventions, and on the expertise of the surgical team. Application of topical Mitomycin c during surgery reduces the incidence of granulations. Close postoperative follow up for a long time and the necessity of more than one intervention improves results and can spare patients the morbidity and mortality associated with acute airway obstruction.
PubMed: 37275098
DOI: 10.1007/s12070-023-03528-4