Staged Laryngotracheoplasty in Adult Laryngotracheal Stenosis

Liu, Isabelle Y.; Mendelsohn, Abie H.; Ching, Harry H.; Long, Jennifer L.; Chhetri, Dinesh K.; Berke, Gerald S.

doi:10.1001/jamaoto.2014.3283

Cited by 19 publications

(14 citation statements)

References 24 publications

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“…In general, the mean age of patients in these studies ranged from 20 to 50 years. 7,15,20,21 While age versus success of decannulation data for each patient was not published in many of these series, the age reported in these studies ranged from 34 to 77 years. Lusk et al reported a TR in a 72-year-old; however, this patient never underwent decannulation.…”

Section: Discussionmentioning

confidence: 99%

“…6 While some authors elucidated risk factors for failure of major open laryngotracheal reconstruction (LTR) among adults-including diabetes mellitus, gastroesophageal reflux, and high-grade stenosisto date no study has focused on the success of major open laryngotracheal operations in the advanced decades. 7,8 In this case series with chart review, we examined our experience of LTR for older adults, aged 60 years, in a tertiary medical center. The goal of this work was to examine the safety, efficacy, and execution of major laryngotracheal operations in the advanced decades.…”

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confidence: 99%

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Laryngotracheal Reconstruction in Adults Aged 60 Years and Older

Rehman

Xie

Bekeny

et al. 2019

Otolaryngol.--head neck surg.

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Objective The primary aim of this study is to evaluate the safety, efficacy, and execution of major open laryngotracheal operations for patients in the advanced decades. Study Design Case series with chart review. Setting Multidisciplinary clinic at a tertiary care academic hospital. Subjects and Methods Patient characteristics, operative course, and postoperative outcomes were retrospectively recorded for all airway reconstruction operations performed between 1999 and 2016 on patients aged ≥60 years Long-term success was defined as prosthesis-free survival at last follow-up. Descriptive statistics were performed. Results Twenty-nine patients met inclusion criteria, and the median age was 71 years (interquartile range, 63-74). Tracheal resection was the most common procedure (13 patients), followed by laryngotracheal reconstruction (7 patients). Fifteen patients began their operation with a tracheostomy, 6 of whom underwent decannulation prior to leaving the operating room. Three additional patients underwent decannulation at follow-up appointments and were prosthesis-free at most recent follow-up. The mean time to decannulation among these patients was 3 months. Of the 14 patients beginning their procedure without a tracheostomy, only 2 required permanent airway prosthesis. The overall long-term rate of prosthesis-free survival was 72.4% (21 of 29 patients). Factors suggestive of long-term success include lower McCaffrey grade and lack of pulmonary disease, hypertension, or diabetes, as well as decreased red blood cell distribution width on preoperative complete blood count. Conclusion Through careful patient selection, preoperative workup, and meticulous postoperative care, airway reconstruction procedures in patients aged ≥60 years are reasonably successful. Of 29 patients, 21 (72.4%) were successfully breathing long-term without airway prosthesis.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Laryngotracheal Reconstruction in Adults Aged 60 Years and Older

Rehman

Xie

Bekeny

et al. 2019

Otolaryngol.--head neck surg.

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“…Our current understanding of the pathologic fibrosis that hallmarks postintubation or iatrogenic LTS (iLTS) relates its development to dysregulated wound healing initiated by endotracheal intubation injury, placing iLTS in the purview of an immunofibrotic disease 4,5 . However, given the cursory understanding of this disease, current strategies for the management of iLTS are primarily surgical and are aimed at relieving obstruction either by dilation, tracheal resection, or tracheostomy 6–8 . Medical treatment strategies aimed at reducing fibrosis in iLTS are of limited benefit.…”

Section: Introductionmentioning

confidence: 99%

“…4,5 However, given the cursory understanding of this disease, current strategies for the management of iLTS are primarily surgical and are aimed at relieving obstruction either by dilation, tracheal resection, or tracheostomy. [6][7][8] Medical treatment strategies aimed at reducing fibrosis in iLTS are of limited benefit. The lack of effective medical therapies for iLTS reflects our deficiencies in understanding the pathogenesis of iLTS and highlights the need for investigation into underlying mechanisms of disease.…”

Section: Introductionmentioning

confidence: 99%

M2 Macrophages Promote Collagen Expression and Synthesis in Laryngotracheal Stenosis Fibroblasts

et al. 2020

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Objective Macrophages exhibit distinct phenotypes and are dysregulated in a model of iatrogenic laryngotracheal stenosis (iLTS). Increased populations of alternatively activated or M2 macrophages have been demonstrated. However, the role of these macrophages is unknown. The aims of this study are: 1) define the macrophage population in iLTS in the context of classically activated or M1 and M2 macrophage phenotypes, and 2) characterize the effect of monocyte‐derived M1 and M2 macrophages on normal airway and LTS‐derived fibroblasts (FBs) in vitro. Study Design Comparative analysis; in vitro controlled study. Methods Immunohistochemical analysis of human iLTS and control specimens was performed to define the macrophage population. In vitro, M1, and M2 macrophages were polarized using M‐CSF + Interferon‐gamma and lipopolysaccharide or Interleukin‐4, respectively. FBs isolated from laryngotracheal scar (LTS‐FBs) and normal tracheal airway (NA‐FBs) in eight patients with iLTS were cocultured with polarized macrophages. Fibrosis gene expression, soluble collagen production, and proliferation were assessed. Results Immunohistochemical analysis revealed increased CD11b + cells (macrophage marker) in laryngotracheal scar specimens (18.3% vs. 8.5%, P = .03) and predominant CD206 (M2) costaining versus CD86 (M1) (51.5% vs. 9.8%, n = 10, P = .001). In vitro, NA‐FBs cultured with M2 macrophages demonstrated a 2.41‐fold increase in collagen‐1 expression (P = .05, n = 8) and an increase in soluble collagen (9.98 vs. 8.875, mean difference: 1.11 95%, confidence interval 0.024–2.192, n = 8, P = .015). Conclusion Increased populations of CD11b cells are present in iLTS specimens and are predominantly CD206+, indicating an M2 phenotype. In vitro, M2 macrophages promoted collagen expression in airway FBs. Targeting macrophages may represent a therapeutic strategy for attenuating fibrosis in iLTS. Level of Evidence NA Laryngoscope, 131:E346–E353, 2021

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“…1,3 The contemporary management of LTS is primarily surgical and includes serial dilation, tracheal or cricotracheal resection, laryngotracheoplasty, and/or permanent tracheostomy. 4,5 Medical therapies available for the management of LTS are limited, reflecting a need for improved understanding of disease pathogenesis.…”

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confidence: 99%

Interferon-γ Treatment of Human Laryngotracheal Stenosis–Derived Fibroblasts

Motz

Samad

Yin

et al. 2017

JAMA Otolaryngol Head Neck Surg

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IMPORTANCE 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. OBJECTIVE To determine whether the TH1 cytokine interferon-γ inhibits the function of LTS-derived fibroblasts in vitro. DESIGN, SETTING, AND PARTICIPANTS This in vitro controlled study included 6 patients with iatrogenic LTS undergoing routine surgical subglottic and tracheal dilation at a single institution. Fibroblasts were isolated from biopsy specimens of laryngotracheal scar and normal-appearing trachea. The presence of fibroblasts was confirmed by an immunohistochemical analysis. Laryngotracheal stenosis–derived fibroblasts were treated with interferon-γ and compared with untreated controls (2 sets of untreated, LTS-derived fibroblasts [media did not contain interferon-γ]) and normal airway fibroblasts (fibroblasts isolated from normal trachea). Data were collected from August 2015 through June 2016. INTERVENTIONS Treatment with interferon-γ, 10 ng/mL. MAIN OUTCOMES AND MEASURES Cellular proliferation, fibrosis gene expression (using quantitative reverse transcription polymerase chain reaction analysis), soluble collagen, and cellular histologic features were assessed. RESULTS Among the 6 patients (6 women; mean [SD] age, 38.3 [17.2] years), LTS-derived fibroblast proliferation was reduced in patients who received interferon-γ treatment compared with untreated controls on days 3 (mean difference, −6515 cells; 95% CI, −10 630 to −2600 cells) to 6 (mean difference, −47 521 cells; 95% CI, −81285 to −13 757 cells). Interferon-γ treatment reduced collagen types I and III gene expression by 86% and 68%, respectively, and resulted in lower total collagen production (10.94 vs 14.89 μg/mL). In addition, interferon-γ treatment resulted in a 32% reduction in expression of transforming growth factor β in LTS-derived fibroblasts. CONCLUSIONS AND RELEVANCE Interferon-γ reduced proliferation, soluble collagen production, and collagen expression in LTS-derived fibroblasts while also reducing the expression of the profibrotic cytokine transforming growth factor β. These findings suggest that therapeutics aimed at increasing interferon-γ and the TH1 response could attenuate LTS.

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Staged Laryngotracheoplasty in Adult Laryngotracheal Stenosis

Abstract: Staged LTP is an option for the reconstruction laryngotracheal stenosis. Our experience shows excellent decannulation rates in the selected patients with stenosis, many of whom have failed treatment with other surgical modalities.

Cited by 19 publications

References 24 publications

Laryngotracheal Reconstruction in Adults Aged 60 Years and Older

Laryngotracheal Reconstruction in Adults Aged 60 Years and Older

M2 Macrophages Promote Collagen Expression and Synthesis in Laryngotracheal Stenosis Fibroblasts

Interferon-γ Treatment of Human Laryngotracheal Stenosis–Derived Fibroblasts

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