Quantitative Assessment of the Immune Microenvironment in Patients With Iatrogenic Laryngotracheal Stenosis.

OBJECTIVE: Iatrogenic laryngotracheal stenosis (iLTS) is characterized by fibroinflammatory narrowing of the upper airway and is most commonly caused by intubation injury. Evidence suggests a key role for CD4 T cells in its pathogenesis. The objective of this study is to validate emerging multiplex immunofluorescence (mIF) technology for use in the larynx and trachea while quantitatively characterizing the immune cell infiltrate in iLTS. In addition to analyzing previously unstudied immune cell subsets, this study aims to validate previously observed elevations in the immune checkpoint PD-1 and its ligand PD-L1 while exploring their spatial and cellular distributions in the iLTS microenvironment. STUDY DESIGN: Controlled ex vivo cohort study. SETTING: Tertiary care center. METHODS: mIF staining was performed with formalin-fixed, paraffin-embedded slides from 10 patients with iLTS who underwent cricotracheal resection and 10 control specimens derived from rapid autopsy for CD4, CD8, CD20, FoxP3, PD-1, PD-L1, and cytokeratin. RESULTS: There was greater infiltration of CD4+ T cells, CD8+ T cells, CD20+ B cells, FoxP3+CD4+ Tregs, and FoxP3+CD8+ early effector T cells in the submucosa of iLTS specimens as compared with controls (P < .05 for all). PD-1 was primarily expressed on T cells and PD-L1 predominantly on CD4+ cells and "other" cells. CONCLUSION: This study leverages the power of mIF to quantify the iLTS immune infiltrate in greater detail. It confirms the highly inflammatory nature of iLTS, with CD4+ cells dominating the immune cell infiltrate; it further characterizes the cellular and spatial distribution of PD-1 and PD-L1; and it identifies novel immunologic targets in iLTS.

Health Care Costs and Cost-effectiveness in Laryngotracheal Stenosis.

OBJECTIVE: Laryngotracheal stenosis (LTS) is resource-intensive disease. The cost-effectiveness of LTS treatments has not been adequately explored. We aimed to conduct a cost-effectiveness analysis comparing open reconstruction (cricotracheal/tracheal resection [CTR/TR]) with endoscopic dilation in the treatment of LTS. STUDY DESIGN: Retrospective cohort. SETTING: Tertiary referral center (2013-2017). SUBJECTS AND METHODS: Thirty-four LTS patients were recruited. Annual costs were derived from the Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University. Cost-effectiveness analysis compared CTR/TR versus endoscopic dilation at a willingness-to-pay threshold of $50,000 per quality-adjusted life year (QALY) over 5- and 10-year time horizons. The incremental cost-effectiveness ratio (ICER) was calculated with deterministic analysis and tested for sensitivity with univariate and probabilistic sensitivity analysis. RESULTS: Mean LTS costs were $4080.09 (SE, $569.29) annually for related health care visits. The major risk factor for increased cost was etiology of stenosis. As compared with idiopathic patients, patients with intubation-related stenosis had significantly higher annual costs ($5286.56 vs $2873.62, P = .03). The cost of CTR/TR was $8583.91 (SE, $2263.22). Over a 5-year time horizon, CTR/TR gained $896 per QALY over serial dilations and was cost-effective. Over a 10-year time horizon, CTR/TR dominated dilations with a lower cost and higher QALY. CONCLUSION: The cost of treatment for LTS is significant. Patients with intubation-related stenosis have significantly higher annual costs than do idiopathic patients. CTR/TR contributes significantly to cost in LTS but is cost-effective versus endoscopic dilations for appropriately selected patients over a 5- and 10-year horizon.

Short- and long-term outcomes of oropharyngeal cancer care in the elderly.

OBJECTIVE: To examine associations between pretreatment variables, short-term and long-term swallowing and airway impairment, and survival in elderly patients (age > 65 years) treated for oropharyngeal squamous cell cancer (SCCA). STUDY DESIGN: Retrospective analysis of Surveillance, Epidemiology, and End Results (SEER)-Medicare data. METHODS: Longitudinal data from 666 patients diagnosed with oropharyngeal SCCA from 2004 to 2007 were evaluated using cross-tabulations, multivariate logistic regression, and survival analysis. RESULTS: Dysphagia (odds ratio [OR] = 1.3, 1.0-1.7), esophageal stricture (OR = 5.5, 2.6-11.9), and airway obstruction (OR = 1.6, 1.1-2.2) increased 1 year after treatment. The odds of airway obstruction, esophageal stricture, and pneumonia increased over subsequent years, with significantly increased risk at 5 years for airway obstruction (OR = 3.0, 1.4-6.4), pneumonia (OR = 4.5, 1.8-11.2), and stricture (OR = 5.5, 1.8-17.6). Pretreatment dysphagia was a significant predictor of long-term dysphagia, airway obstruction, and pneumonia. Chemoradiation, advanced stage disease, high-volume hospital care, male sex, and salvage surgery were significant predictors of long-term gastrostomy use. Long-term dysphagia, gastrostomy or tracheostomy dependence, weight loss, airway obstruction, and pneumonia were associated with poorer survival, with tracheostomy dependence (hazard ratio [HR] = 2.2, 1.7-2.9) and pneumonia (HR = 2.0, 1.7-2.4) associated with the greatest risk of late mortality. CONCLUSION: Airway and swallowing impairment is common after treatment of oropharyngeal SCCA in elderly patients, increases over time, and is associated with poorer survival. Patients with pretreatment dysphagia, advanced stage disease, initial treatment with chemoradiation, and salvage surgery represent a high-risk group with an increased risk of disability and death. LEVEL OF EVIDENCE: 2c. Laryngoscope, 128:2084-2093, 2018.

Association of Transoral Robotic Surgery With Short-term and Long-term Outcomes and Costs of Care in Oropharyngeal Cancer Surgery.

Importance: The treatment of oropharyngeal cancer has undergone a paradigm shift in the past 2 decades, with an increase in the use of nonoperative treatment owing to poor functional outcomes associated with traditional surgical approaches. Transoral robotic surgery (TORS) allows surgical resection of oropharyngeal cancer (OPC) with less morbidity through a minimally invasive approach. Objective: To investigate the relationship among TORS and short- and long-term outcomes and costs in surgically treated patients with OPC. Design, Setting, and Participants: Retrospective cross-sectional analysis of 3573 patients who underwent an ablative procedure for OPC in 2010 to 2012 using the MarketScan Commercial Claim and Encounters database. Main Outcomes and Measures: The association between TORS and short- and long-term outcomes, length of hospitalization, and treatment-related costs was analyzed using descriptive statistics and multivariate regression modeling. Results: Transoral robotic surgery was performed in 304 surgical cases (8.5%); 94.7% of patients were 40 to 64 years old, and 70.7% were male. The use of TORS increased from 4.1% of surgical cases in 2010 to 13.2% of surgical cases in 2012. Patients who underwent TORS had a lower rate of tracheotomy during treatment (3.9% vs 11.4%), and posttreatment gastrostomy tube use (21.9% vs 34.2%), compared with patients undergoing non-TORS procedures. On multivariate analysis, TORS was not associated with significant differences in postoperative complications or length of hospitalization. There was no significant difference in the odds of receiving postoperative radiation therapy between patients who underwent TORS and those who did not; however, among patients receiving radiation therapy, chemoradiation was significantly less likely following TORS (odds ratio [OR], 0.52; 95% CI, 0.29-0.90). TORS was associated with significantly decreased odds of posttreatment gastrostomy (OR, 0.54; 95% CI. 0.30-0.95) and tracheostomy during treatment (OR, 0.17; 95% CI, 0.06-0.55) at 1 year, and was associated with significantly decreased overall treatment-related costs of care (mean incremental cost, -$22 724). Conclusions and Relevance: The use of TORS for surgical resection of OPC is increasing in the United States and is associated with significantly lower use of adjuvant chemoradiation, late gastrostomy and tracheostomy dependence, and lower overall treatment-related costs of care. These data have implications for discussions of value in OPC care at a time of health care reform.