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Journal of Biomechanical Engineering Feb 2024Acquired subglottal stenosis is an unpredicted complication that can occur in some patients who have undergone prolonged endotracheal intubation. It is a narrowing of...
Acquired subglottal stenosis is an unpredicted complication that can occur in some patients who have undergone prolonged endotracheal intubation. It is a narrowing of the airway at the level of the cricoid cartilage that can restrict airflow and cause breathing difficulty. Stenosis is typically treated with endoscopic airway dilation, with some patients experiencing multiple recurrences. The study highlights the potential of computational fluid dynamics as a noninvasive method for monitoring subglottic stenosis, which can aid in early diagnosis and surgical planning. An anatomically accurate human laryngeal airway model was constructed from computerized tomography (CT) scans. The subglottis cross-sectional area was narrowed systematically using ≈10% decrements. A quadratic profile was used to interpolate the transformation of the airway geometry from its modified shape to the baseline geometry. The numerical results were validated by static pressure measurements conducted in a physical model. The results show that airway resistance follows a squared ratio that is inversely proportional to the size of the subglottal opening (R∝A-2). The study found that critical constriction occurs in the subglottal region at 70% stenosis (upper end of grade 2). Moreover, removing airway tissue below 40% stenosis during surgical intervention does not significantly decrease airway resistance.
Topics: Humans; Cricoid Cartilage; Vocal Cords; Constriction, Pathologic; Constriction; Larynx
PubMed: 37943109
DOI: 10.1115/1.4064029 -
The Value of Computed Tomography in Recurrent Laryngeal Cancer Following Organ Preservation Therapy.Current Medical Imaging Oct 2023This study aims to assess the accuracy of computed tomography (CT) in detecting recurrent laryngeal tumors after failed chemoradiation therapy (CRT).
AIM
This study aims to assess the accuracy of computed tomography (CT) in detecting recurrent laryngeal tumors after failed chemoradiation therapy (CRT).
BACKGROUND
Local recurrence of laryngeal tumors following CRT has been reported in approximately 25%, yet it is often difficult to detect.
METHODS
Ten patients with laryngeal cancer who failed CRT and subsequently underwent salvage total laryngectomy were included. The laryngeal subsites involved in the tumor were identified based on postoperative pathology. The corresponding preoperative CT scans were selected for review by seven experts (head-and-neck surgeons or radiologists) who scored the extent of tumor spread on each scan on a 5-point scale, from no tumor detected to clearly visible tumor.
RESULTS
The rates of high tumor detectability (scores 4-5) varied according to laryngeal subsite, from 75% in the glottic region, to 45% in the subglottic region, and to 19% in the supraglottic region (P=0.01). The detectability rates were higher on scans performed 2 years or more after CRT.
CONCLUSION
The CT evaluation of laryngeal cancer after CRT has limited value, particularly in the epiglottis and subglottis.
PubMed: 37881089
DOI: 10.2174/0115734056240028231016074150 -
Cancer Imaging : the Official... Oct 2023Accuracy of head and neck MRI (HN-MRI) in predicting tumor invasion of laryngeal site/subsites in patients with laryngeal cancer prior to laryngectomy is poorly...
BACKGROUND
Accuracy of head and neck MRI (HN-MRI) in predicting tumor invasion of laryngeal site/subsites in patients with laryngeal cancer prior to laryngectomy is poorly evaluated in the literature. Therefore, we aim to evaluate the diagnostic value of HN-MRI in accurate pre-operative estimation of tumor invasion to laryngeal subsites in patients with laryngeal cancer.
METHODS
Patients with laryngeal cancer who underwent HN-MRI for cancer staging and underwent total laryngectomy between 2008 and 2021 were included. Sensitivity, specificity, positive predictive value, negative predictive value, and overall accuracy of HN-MRI in predicting tumor invasion of laryngeal subsites were calculated based on concordance between the HN-MRI and histopathological results.
RESULTS
One hundred and thirty-seven patients underwent total laryngectomy [primary: 82/137(60%), salvage 55/137(40%)]. The utilization of HN-MRI resulted in the downstaging of 16/137 (11.6%) patients and the upstaging of 8/137 (5.8%) patients. For the whole cohort, there was a significant discordance between HN-MRI and histopathology for T-category; out of 116 cT4a disease, 102(87.9%) were confirmed to have pT4a disease, and out of 17 cT3 disease, 9(52.9%) were confirmed to have pT3 disease, p < 0.001. The MRI overall diagnostic accuracy of predicting tumor invasion was 91%, 92%, 82%, 87%, 72%, 76%, 65% and 68% for base of tongue, arytenoid, vocal cord, posterior commissure, pre-epiglottic space, cricoid cartilage, inner thyroid cortex, and subglottis, respectively.
CONCLUSIONS
In patients with laryngeal cancer undergoing total laryngectomy, HN-MRI demonstrates promising accuracy in predicting tumor invasion of specific laryngeal subsites (e.g., base of tongue). Our findings showed the potential of HN-MRI as a valuable tool for pre-operative planning and treatment decision-making in this patient population.
Topics: Humans; Laryngeal Neoplasms; Neoplasm Invasiveness; Magnetic Resonance Imaging; Neoplasm Staging; Laryngectomy; Retrospective Studies
PubMed: 37858162
DOI: 10.1186/s40644-023-00618-y -
Computers in Biology and Medicine Nov 2023The efficacy of inhalation therapy depends on the drug deposition in the human respiratory tract. This study investigates the effects of vocal fold adduction on the...
BACKGROUND
The efficacy of inhalation therapy depends on the drug deposition in the human respiratory tract. This study investigates the effects of vocal fold adduction on the particle deposition in the glottis.
METHODS
A realistic mouth-throat (MT) geometry was built based on CT images of a healthy adult (MT-A). Mild (MT-B) and great (MT-C) vocal fold (VF) adduction were incorporated in the original model. Monodisperse particles range in size from 3 to 12 μm were simulated at inspiration flow rates of 15, 30 and 45 L per minute (LPM). The regional deposition of drug aerosols was performed in 3D-printed models and quantified using high-performance liquid chromatography.
RESULTS
Both the numerical analysis and in vitro experiments show that most particles are deposited in the mouth, pharynx and supraglottis, while few are deposited in the glottis and subglottis. For most cases in MT-A, the particle quantity in glottis is lower than 0.02 N/mm at 15 and 30 LPM while they increase dramatically at 45 LPM. It peaked at 0.347 N/mm for 5-μm particles at 45 LPM in MT-B and 2.324 N/mm for 6-μm particles at 30 LPM in MT-C. The lowest drug mass faction in the glottis in vitro were found at 15 LPM for MT-A and MT-C, and at 30 LPM for MT-B, whereas it peaked at 45 LPM for all MT models, 0.71% in MT-A, 1.16% in MT-B, and 2.53% in MT-C, respectively.
CONCLUSION
Based on the results of this study, larger particles are more likely to be deposited in the oral cavity, oropharynx, and supraglottis than in the glottis. However, particle deposition in the glottis generally increases with VF adduction and greater inspiratory flow rates.
Topics: Humans; Glottis; Vocal Cords; Models, Biological; Aerosols; Adult; Male; Models, Anatomic; Tomography, X-Ray Computed
PubMed: 37820560
DOI: 10.1016/j.compbiomed.2023.107537 -
The Laryngoscope Apr 2024Recent translational scientific efforts in subglottic stenosis (SGS) support a disease model where epithelial alterations facilitate microbiome displacement,...
OBJECTIVES
Recent translational scientific efforts in subglottic stenosis (SGS) support a disease model where epithelial alterations facilitate microbiome displacement, dysregulated immune activation, and localized fibrosis. Given the observed immune cell infiltrate in SGS, we sought to test the hypothesis that SGS cases possessed a low diversity (highly clonal) adaptive immune response when compared with healthy controls.
METHODS
Single cell RNA sequencing (scRNA-seq) of subglottic mucosal scar in iSGS (n = 24), iLTS (n = 8), and healthy controls (n = 7) was performed. T cell receptor (TCR) sequences were extracted, analyzed, and used to construct repertoire structure, compare diversity, interrogate overlap, and define antigenic targets using the Immunarch bioinformatics pipeline.
RESULTS
The proximal airway mucosa in health and disease are equally diverse via Hill framework quantitation (iSGS vs. iLTS vs. Control, p > 0.05). Repertoires do not significantly overlap between individuals (Morisita <0.02). Among iSGS patients, clonality of the TCR repertoire is driven by CD8+ T cells, and iSGS patients possess numerous TCRs targeting viral and intercellular pathogens. High frequency clonotypes do not map to known targets in public datasets.
CONCLUSION
SGS cases do not possess a lower diversity adaptive immune infiltrate when compared with healthy controls. Interestingly, the TCR repertoire in both health and disease contains a restricted number of high frequency clonotypes that do not significantly overlap between individuals. The target of the high frequency clonotypes in health and disease remain unresolved.
LEVEL OF EVIDENCE
NA Laryngoscope, 134:1757-1764, 2024.
Topics: Humans; Receptors, Antigen, T-Cell; CD8-Positive T-Lymphocytes; Laryngostenosis
PubMed: 37787469
DOI: 10.1002/lary.31088 -
The Annals of Otology, Rhinology, and... Feb 2024The primary objective is to describe a case in which a steroid-eluting implant was utilized to help prevent postoperative granulation and restenosis in a patient who...
OBJECTIVES
The primary objective is to describe a case in which a steroid-eluting implant was utilized to help prevent postoperative granulation and restenosis in a patient who underwent double-stage laryngotracheal reconstruction (dsLTR) for subglottic stenosis.
METHODS
This case presents a 3-year-old female who underwent dsLTR with anterior cartilage graft placement and posterior sagittal split for subglottic stenosis. A silicone stent was placed at the time of the dsLTR. After stent removal, direct laryngoscopy and bronchoscopy (DLB) was performed at 4 to 5 week intervals. These visits revealed a significant amount of supraglottic and glottic edema, and granulation tissue at the proximal aspect of the graft contributing to airway obstruction and restenosis. This was treated twice with CO laser excision, balloon dilation, and triamcinolone injection. On the third treatment with these modalities, a mometasone furoate implant was inserted as an adjunctive therapy. The implant was inserted to lateralize the vocal folds, prevent webbing, and to extend to the narrowed area within the subglottis to prevent granulation and restenosis. These same treatments were repeated at the fourth visit with another mometasone furoate implant of a smaller size placed in the same location.
RESULTS
Findings on DLB since treatment with the steroid-eluting implants have shown persistent granulation tissue limited to the tracheostomy stoma site. Treatments with CO laser, balloon dilation, and triamcinolone injection have continued, with occasional use of silver nitrate cautery at the external stoma site. There has not been any significant evidence of edema, granulation, or stenosis in the glottis or subglottis to require another steroid-eluting implant.
CONCLUSIONS
Steroid-eluting implants appear to be a safe and effective adjunctive therapy in the routine surveillance of pediatric patients with a tracheostomy who have undergone dsLTR. They may help combat granulation formation and restenosis seen in some dsLTR patients.
Topics: Child, Preschool; Female; Humans; Carbon Dioxide; Constriction, Pathologic; Edema; Laryngostenosis; Mometasone Furoate; Retrospective Studies; Treatment Outcome; Triamcinolone
PubMed: 37776286
DOI: 10.1177/00034894231202067 -
The Annals of Otology, Rhinology, and... Feb 2024Gain insights into the pathophysiology of idiopathic subglottic stenosis (iSGS) by investigating differences in transcriptome of subglottic mucosal tissue between...
OBJECTIVES
Gain insights into the pathophysiology of idiopathic subglottic stenosis (iSGS) by investigating differences in transcriptome of subglottic mucosal tissue between patients with iSGS and controls, and between tracheal and subglottic tissue within patients.
METHODS
RNA sequencing was conducted on biopsied mucosal samples collected from subglottic and tracheal (in-patient control) regions in iSGS patients, and from subglottis in controls. The gene expression differences were validated on a protein level by (1) staining the tissue samples obtained from a second cohort of patients and controls; and (2) in vitro functional assays using primary subglottic epithelial cells from both iSGS patients and healthy donors.
RESULTS
We found 7 upregulated genes in the subglottic region of iSGS patients relative to both the tracheal mucosa and subglottic region of controls. A gene ontology enrichment analysis found that the epithelial cell differentiation and cornification pathways are significant, involving specifically 3 of the genes: involucrin (), small proline rich protein 1B (), and keratin 16 (). Involvement of these pathways suggests squamous metaplasia of the epithelium. Histological analyses of epithelium in subglottic mucosal biopsies revealed squamous metaplasia in 41% of the samples from iSGS patients and in 25% from controls. Immunohistochemical evaluation of the samples presented with squamous epithelium revealed increased expression of the protein encoded by , hyperproliferative basal cells, shedding of apical layers, and accompanying lesions in iSGS compared to CTRL. Cultured primary subglottic epithelial cells from iSGS patients had higher proliferation rates compared to healthy donors and squamous metaplastic differentiation formed thinner epithelia with increased expression proteins encoded by , , and , suggesting intrinsic dysfunction of basal cells in iSGS.
CONCLUSIONS
Abnormal squamous differentiation of epithelial cells may contribute to the pathogenesis of iSGS. Patients having metaplastic epithelial phenotype may be sensitive to drugs that reverse it to a normal phenotype.
Topics: Humans; Constriction, Pathologic; Laryngostenosis; Larynx; Cornified Envelope Proline-Rich Proteins; Metaplasia; Carcinoma, Squamous Cell
PubMed: 37740367
DOI: 10.1177/00034894231201016 -
Journal of Cancer Research and... Aug 2023An 8-year-old child was admitted to our ENT department for a year because of a hoarse voice. An endoscopic examination displayed that a cystic, solid lesion can be seen... (Review)
Review
An 8-year-old child was admitted to our ENT department for a year because of a hoarse voice. An endoscopic examination displayed that a cystic, solid lesion can be seen in the right subglottis. The lesion was removed using a CO2 laser under general anesthesia. Postoperative histopathology confirmed granular cell tumor (GCT), S-100(+), vimentin (+), and SOX-10(+). GCT, also known as the Abrikossoff tumor, is a rare benign tumor that rarely occurs in the larynx, particularly in children. This case report emphasizes that considerable attention should be given to the differential diagnosis of the laryngeal granulosa cell tumor. Given the recurrence risk of GCT, long-term postoperative follow-up is necessary.
Topics: Female; Humans; Child; Granular Cell Tumor; Larynx; Anesthesia, General; Diagnosis, Differential; Ovarian Neoplasms
PubMed: 37675739
DOI: 10.4103/jcrt.jcrt_2096_22 -
Otolaryngology--head and Neck Surgery :... Jan 2024To narrow knowledge gaps in the pathophysiology of idiopathic subglottic stenosis (iSGS) through comparison of a murine subglottic stenosis model with iSGS.
OBJECTIVE
To narrow knowledge gaps in the pathophysiology of idiopathic subglottic stenosis (iSGS) through comparison of a murine subglottic stenosis model with iSGS.
STUDY DESIGN
In vivo animal study.
SETTING
Academic institution.
METHODS
Murine samples/measurements were obtained from mice that underwent chemomechanical injury with a wire brush and bleomycin. Human samples/measurements were obtained from iSGS patients. Anatomic, physiologic, and epithelial molecular data were collected using histology, human peak expiratory flow (PEF) and murine airway conductance, gene expression analysis with quantitative polymerase chain reaction, and protein analysis with quantitative immunohistochemistry.
RESULTS
Anatomic patterns of scars at the subglottis and proximal trachea seen in the murine model are similar to iSGS patients. Subglottic stenosis (SGS) mice had a decrease (P = .0194) in airway conductance compared to healthy controls, similar to a decrease (P = .0001) in predilation PEF versus postdilation in iSGS patients. There was decreased epithelial gene expression of E-cadherin (ECAD) (P < 0.01), occludin (OCLN) (P < .01), and cytokeratin-5 (CK5) (P < .05) and protein expression of ECAD (H/M: P < .001), OCLN (H: P < 0.05, M: P < .001), and CK5 (H: P < .001, M: P < .01) in murine SGS and iSGS versus controls.
CONCLUSION
The murine SGS model shows anatomic, physiologic, and molecular congruency with human iSGS, making it a reasonable model to investigate iSGS. The molecular similarities in epithelial barrier dysfunction suggest it may best be suited to explore epithelial mechanisms of iSGS and therapies directed at epithelial reconstitution. This model provides a foundation to collect data that will improve understanding of iSGS, and, ultimately, translate into more accurate animal models for future use.
Topics: Humans; Animals; Mice; Constriction, Pathologic; Disease Models, Animal; Pulmonary Fibrosis; Laryngostenosis; Larynx; Fibrosis
PubMed: 37622571
DOI: 10.1002/ohn.502