design-biocompatible-drug-eluting-tracheal-stent-mice-with

Design of a Biocompatible Drug-Eluting Tracheal Stent in Mice with Laryngotracheal Stenosis

Laryngotracheal stenosis (LTS) is a pathologic narrowing of the subglottis and trachea leading to extrathoracic obstruction and significant shortness of ...

Johns Hopkins School of Medicine

The presence of human papillomavirus (HPV) in unknown primary squamous cell carcinoma (UPSCC) of the head and neck at initial presentation focuses the investigation for the primary tumor on the oropharynx. The trends, frequency, and detection rate of UPSCCs have not been evaluated in the context of HPV tumor status.

Changes in Unknown Primary Squamous Cell Carcinoma of the Head and Neck at Initial Presentation in the Era of Human Papillomavirus.

This review will highlight the indications and benefits of office-based therapy for recurrent respiratory papillomatosis (RRP) and discuss the utilization of photo-dynamic lasers and adjuvant medical therapy in office-based settings. Office-based management of RRP allows for more timely interventions, is preferred by the majority of patients, and negates the risk of general anesthesia. Current literature argues for the utilization of KTP laser over CO laser for office-based treatment of RRP. Medical therapies for RRP are limited, but agents such as bevacizumab are promising and have been shown to reduce disease burden. Medical therapies that can induce disease remission are still needed. Office-based procedures save time and healthcare expenses compared to like procedures in the operating room. However, the increased frequency for office-based procedures predicts similar overall healthcare costs for office-based and OR laser excision of RRP. Office-based management of RRP is a feasible and well-tolerated strategy in appropriately selected patients with adequate local anesthesia.

Office-based Management of Recurrent Respiratory Papilloma.

Objective Laryngotracheal stenosis (LTS) is a fibrotic process that narrows the upper airway and has a significant impact on breathing and phonation. Iatrogenic injury from endotracheal and/or tracheostomy tubes is the most common etiology. This study investigates differences in LTS etiologies as they relate to tracheostomy dependence and dilation interval. Study Design Case series with chart review. Setting Single-center tertiary care facility. Subjects and Methods Review of adult patients with LTS was performed between 2004 and 2015. The association of patient demographics, comorbidities, disease etiology, and treatment modalities with patient outcomes was assessed. Multiple logistic regression analysis and Kaplan-Meier analysis were performed to determine factors associated with tracheostomy dependence and time to second procedure, respectively. Results A total of 262 patients met inclusion criteria. Iatrogenic patients presented with greater stenosis ( P = .023), greater length of stenosis ( P = .004), and stenosis farther from the vocal folds ( P < .001) as compared with other etiologies. Iatrogenic patients were more likely to be African American, use tobacco, and have obstructive sleep apnea, type II diabetes, hypertension, chronic obstructive pulmonary disease, or a history of stroke. Iatrogenic LTS (odds ratio [OR] = 3.1, 95% confidence interval [95% CI] = 1.2-8.2), Cotton-Myer grade 3-4 (OR = 2.6, 95% CI = 1.1-6.4), and lack of intraoperative steroids (OR = 2.9, 95% CI = 1.2-6.9) were associated with tracheostomy dependence. Nonsmokers, patients without tracheostomy, and idiopathic LTS patients had a significantly longer time to second dilation procedure. Conclusion Iatrogenic LTS presents with a greater disease burden and higher risk of tracheostomy dependence when compared with other etiologies of LTS. Comorbid conditions promoting microvascular injury-including smoking, COPD, and diabetes-were prevalent in the iatrogenic cohort. Changes in hospital practice patterns to promote earlier tracheostomy in high-risk patients could reduce the incidence of LTS.

Laryngotracheal Stenosis: Risk Factors for Tracheostomy Dependence and Dilation Interval

Objectives (1) Develop a novel method for serial assessment of gene and protein expression in laryngotracheal stenosis (LTS). (2) Assess cytokine expression and determine an immunophenotype in LTS. Study Design A matched comparison of endolaryngeal brush biopsy samples from laryngotracheal scar and normal airway. Setting Tertiary care hospital, 2015-2016. Methods Brush biopsy specimens of laryngotracheal scar and normal trachea were obtained from 17 patients with LTS at the time of operating room dilation and were used for protein and RNA extraction. Gene expression of the T1 cytokine interferon γ (INF-γ), T2 cytokine interleukin 4 (IL-4), transforming growth factor β, and collagen 1 (Coll1) was quantified with quantitative real-time polymerase chain reaction. Cytokine analysis was performed with flow cytometry with a cytometric bead array. Results LTS specimens demonstrated a 13.68-fold increase in Coll1 gene expression versus normal ( P < .001, N = 17). Additionally, IL-4 gene expression showed a 3.76-fold increase ( P < .001, N = 17) in LTS scar. When stratified into iatrogenic LTS and idiopathic subglottic stenosis cohorts, INF-γ gene expression was significantly increased in idiopathic subglottic stenosis ( P = .011). Soluble cytokine measurements were below the limit of detection for reliable quantification and thus could not be assessed. Conclusions Brush biopsies from LTS samples can be successfully utilized for RNA extraction and demonstrate the expected increase in Coll1 gene expression associated with LTS. Preliminary gene expression suggests that abnormal collagen production may be mediated by the T2 cytokine IL-4 and that increased INF-γ expression may represent a key difference between iatrogenic LTS and idiopathic subglottic stenosis. Further analysis of soluble cytokines is needed to confirm these findings.

Quantification of Inflammatory Markers in Laryngotracheal Stenosis.

Laryngotracheal stenosis (LTS) is a fibroproliferative disorder of the glottis, subglottis, and trachea. In models of fibrosis from other organ systems, the CD4+ T-cell response has been shown to regulate extracellular matrix deposition. Specifically, helper T cell 2 (TH2) promotes fibrosis, whereas TH1 and associated cytokines have been shown to be antifibrotic. However, this antifibrotic effect of the TH1 response has not been demonstrated in LTS.

Interferon-γ Treatment of Human Laryngotracheal Stenosis-Derived Fibroblasts.

Management of laryngotracheal stenosis (LTS) remains primarily surgical, with a critical need to identify targets for adjuvant therapy. Laryngotracheal stenosis scar fibroblasts exhibit a profibrotic phenotype with distinct metabolic shifts, including an increased glycolysis/oxidative phosphorylation ratio. This study examines the effects of the glutamine antagonist 6-diazo-5-oxo-l-norleucine (DON) on collagen production, gene expression, proliferation, and metabolism of human LTS-derived fibroblasts in vitro.

Targeting metabolic abnormalities to reverse fibrosis in iatrogenic laryngotracheal stenosis.

This prospective controlled human and murine study assessed the presence of inflammatory cells and cytokines to test the hypothesis that immune cells are associated with fibroproliferation in iatrogenic laryngotracheal stenosis (iLTS).

T-Helper 2 Lymphocyte Immunophenotype Is Associated With Iatrogenic Laryngotracheal Stenosis.

Develop a drug-eluting stent construct with a reliable drug-release profile and adequate mechanically stability for a trial in a small animal model of laryngotracheal stenosis (LTS), a debilitating pathologic narrowing of the airway leading to significant shortness of breath.

Engineering an immunomodulatory drug-eluting stent to treat laryngotracheal stenosis.

Glutamine metabolism is a critical energy source for iatrogenic laryngotracheal stenosis (iLTS) scar fibroblasts, and glutaminase (GLS) is an essential enzyme converting glutamine to glutamate. We hypothesize that the GLS-specific inhibitor BPTES will block glutaminolysis and reduce iLTS scar fibroblast proliferation, collagen deposition, and fibroblast metabolism in vitro.

Article	Year
Changes in Unknown Primary Squamous Cell Carcinoma of the Head and Neck at Initial Presentation in the Era of Human Papillomavirus. JAMA otolaryngology-- head & neck surgery\| PubMed ID: 26769661	2016
Office-based Management of Recurrent Respiratory Papilloma. Current otorhinolaryngology reports\| PubMed ID: 27242951	2016
Laryngotracheal Stenosis: Risk Factors for Tracheostomy Dependence and Dilation Interval Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery\| PubMed ID: 28112014	2017
Quantification of Inflammatory Markers in Laryngotracheal Stenosis. Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery\| PubMed ID: 28485188	2017
Interferon-γ Treatment of Human Laryngotracheal Stenosis-Derived Fibroblasts. JAMA otolaryngology-- head & neck surgery\| PubMed ID: 28715559	2017
Targeting metabolic abnormalities to reverse fibrosis in iatrogenic laryngotracheal stenosis. The Laryngoscope\| PubMed ID: 28940431	2018
T-Helper 2 Lymphocyte Immunophenotype Is Associated With Iatrogenic Laryngotracheal Stenosis. The Laryngoscope\| PubMed ID: 30421427	2019
Engineering an immunomodulatory drug-eluting stent to treat laryngotracheal stenosis. Biomaterials science\| PubMed ID: 30874257	2019
Inhibition of glutaminase to reverse fibrosis in iatrogenic laryngotracheal stenosis. The Laryngoscope\| PubMed ID: 31904876	2020

Kevin Motz

Biography

JoVE Journal Publications

Other Publications