Edell, Eric S.

Abstract Objective To evaluate whether systemic hormone replacement therapy (HRT) influences recurrence outcomes in postmenopausal patients with idiopathic subglottic stenosis (iSGS). Study Design Retrospective cohort study. Setting Tertiary academic medical center. Methods Postmenopausal women (≥50 years) with iSGS who underwent laser‐wedge excision between 2002 and 2024 were included. Patients were categorized by systemic HRT exposure (oral estrogen, progesterone, combined estrogen‐progesterone, or transdermal estrogen) at or before their first surgery. Overdispersion was assessed for all Poisson models; given significant overdispersion, negative binomial regression with a log‐offset for follow‐up time was used as the primary model. Surgery‐free intervals were analyzed using linear mixed models, and time to first recurrence using Cox regression. Models were adjusted for age, body mass index (BMI), parity, oophorectomy, follow‐up length, surgery type, and serial intralesional steroid injections (SILSI) use. Results Among 125 patients, 96 had never used HRT (Never HRT) and 29 used HRT, including 19 actively using HRT at presentation (Current HRT), 5 past users, and 5 subsequent users. The HRT versus Never‐HRT recurrence rate comparison was not significant (adjusted incidence rate ratio [IRR] = 0.81, 95% CI: 0.48‐1.37, P = .422). However, Current HRT use was associated with a 53% lower adjusted recurrence rate versus Never‐HRT use (adjusted IRR = 0.47, 95% CI: 0.25, 0.89, P = .0203). Surgery‐free intervals and time to first recurrence trended longer in Current HRT users but were not statistically significant. Conclusion Current HRT use at presentation was associated with significantly fewer recurrences in postmenopausal iSGS patients. These findings may inform individualized, shared decision‐making regarding HRT use in this population. Level of Evidence 3.

Abstract Introduction Nuclear protein in testis (NUT) carcinoma, formerly known as NUT midline carcinoma, is a rare and highly aggressive subtype of squamous cell carcinoma characterized by NUTM1 gene rearrangements. It typically affects children and young adults and shows a predilection for midline structures of the head, neck, and thorax. We describe a rare case of NUT carcinoma in an elderly patient presenting with central airway obstruction treated with tumor debulking, devascularization, and pulsed electric field (PEF) ablation. Case An 89-year-old woman on chronic anticoagulation for atrial fibrillation presented with respiratory distress and hemoptysis requiring intubation and mechanical ventilation. Chest CT revealed a developing right lower lobe infiltrate and bronchoscopy demonstrated a non-obstructing right lower lobe endobronchial lesion. Pathology of the lesion confirmed NUT carcinoma but the patient was lost to follow-up. Two months later, she presented with altered mental status and respiratory failure. Imaging revealed a 4.6 x 2.6 cm mass at the level of the cricoid cartilage causing approximately 75% tracheal obstruction with tracheal wall invasion. She underwent rigid bronchoscopy with tumor debulking and devascularization, achieving >80% tracheal patency post-procedure. EBUS-guided PEF ablation was then performed to target residual bulky tumor found in the paratracheal area. Given her age, comorbidities, and poor performance status, palliative chemotherapy was deferred and palliative radiotherapy was offered to limit tumor progression. Discussion NUT carcinoma is a rare and aggressive malignancy with a poor prognosis. This case demonstrates rapid tumor progression leading to respiratory failure within two months of initial diagnosis. Management options for malignant central airway obstruction in non-surgical candidates may include endobronchial debulking and ablative therapies. In this case, EBUS-guided PEF ablation, a non-thermal technique that delivers brief electric pulses to induce tumor apoptosis while sparing adjacent structures, was successfully used to treat residual disease with the goal of reducing marginal regrowth and maintain airway patency. PEF ablation has been described in percutaneous and bronchoscopic management of early stage non-small cell lung cancer; however, its application in central airway obstruction represents an innovative therapeutic approach. Although chemoradiation may be considered when feasible, no standard regimen exists for NUT carcinoma. It typically responds poorly to conventional therapies, underscoring the importance of complementary local treatment strategies in select patients. This case highlights the rapidly progressive course of NUT carcinoma and demonstrates the potential role of PEF ablation as a novel adjunct in the palliative management of malignant central airway obstruction. This abstract is funded by: None

Background: Airway stenting is a critical intervention to restore airway patency, yet complications such as stent migration, mucostasis, airway injury, and granulation tissue formation remain major concerns. Although various covering materials have been explored, the effectiveness of amniotic membrane (AM) as a stent cover has not been evaluated. This study is the first to assess airway-related complications of a novel AM-covered self-expandable metallic stent (SEMS) compared with a commercially available synthetic polymer-covered SEMS. To compare the incidence of stent-related complications between AM-covered SEMS and synthetic polymer-covered SEMS over a 90-day in vivo survival period. Methods: Eight adult Yucatan miniswine were implanted with either an AM-covered or control stent and monitored over 90 days with bronchoscopic evaluations at 4 timepoints. Histologic assessments were performed at termination. Results: Seven animals completed the study (4 AM stents, 3 controls). One control animal was terminated early due to stent expectoration. AM-covered stents were associated with reduced stent migration, mucostasis, and granulation tissue formation compared with controls. Histologic analysis revealed significantly less airway injury and evidence of re-epithelialization with cilia in the AM group; a feature absent in control stents. One animal was excluded at implantation and replaced due to a procedural complication unrelated to the stent. Conclusion: This is the first study to evaluate stent-related complications of AM-covered airway stents. The results demonstrate that AM-covered SEMS reduce airway injury and common complications associated with synthetic polymer-covered stents. These findings suggest that AM-coverings may enhance biocompatibility and integration while mitigating adverse airway responses. Larger studies and human clinical trials are needed to validate these results and explore clinical application.

Abstract Understanding tumor cell dynamics can improve prognosis and treatment but remains limited for lung adenocarcinoma in people who have never smoked (NS-LUAD). With RNA sequencing data from 684 NS-LUAD cases and validation in an independent dataset, we identified three subtypes with distinct phenotypic traits and cell compositions. Additional genomic and histologic data further characterized the subtypes. “Steady,” marked by low proliferation, high alveolar cell fraction, moderate-to-well differentiation, and fewer driver gene alterations, is linked to prolonged survival and low immune evasion. “Proliferative” shows high proliferation markers, TP53 mutations, and gene fusions. “Chaotic,” with high epithelial-to-mesenchymal transition markers, has the worst prognosis, even within stage I tumors. Lacking known molecular or histologic characteristics, this aggressive subtype is solely identified by transcriptomic data. A 60-gene signature recapitulates the classification and predicts survival even within subgroups based on tumor stage or known genomic features, emphasizing its potential for improving early-stage NS-LUAD prognostication in clinical settings. Significance: The transcriptome of 684 NS-LUAD identifies three subtypes with different cellular dynamics and genomic and morphologic features. A 60-gene signature accurately stratifies subjects for mortality risk, even in stage I, offering a potential clinically applicable tool for treatment decision-making in patients with NS-LUAD. See related commentary by Azizi et al., p. 423

ABSTRACT Background Idiopathic subglottic stenosis (iSGS) occasionally affects women of childbearing age. Surgical intervention is the primary treatment, yet limited research exists on factors influencing disease severity. This study explores the impact of hormonal contraception on iSGS recurrence rates and surgery‐free intervals. Methods This retrospective study was conducted at a tertiary academic care center. Patients using hormonal birth control (e.g., estrogen‐progesterone pills, progesterone implants) during their first procedure were classified in “Birth Control (BC)” group, while those not using contraceptives were placed in “No Birth Control (NBC)” group. Poisson regression evaluated recurrence rates, and Mann–Whitney tests assessed surgery‐free intervals. Kaplan–Meier analysis estimated time to first recurrence, adjusting for age and follow‐up duration. Results Twenty‐six patients were in the NBC group and 12 in the BC group (average ages 37 and 34, respectively). Patients in the NBC group were 2.6 times more likely to experience recurrence compared to those in the BC group ( p = 0.001). The expected number of recurrences for the BC group was 0.4 times that of the NBC group (95% CI: 0.2–0.7; p = 0.001). Furthermore, patients taking birth control were significantly less likely to have a first recurrence (HR: 0.4; 95% CI: 0.2–0.9; p = 0.025) and had longer times to first recurrence (Figure 1; p = 0.031). Conclusions Birth control appears to protect against iSGS severity, potentially through hormonal mechanisms. Hormonal contraception may serve as a non‐surgical alternative for managing iSGS. Future prospective studies may evaluate outcomes in newly diagnosed iSGS patients started on birth control compared to those not using hormonal contraceptives. Level of Evidence 3.

ABSTRACT Background Managing idiopathic subglottic stenosis (iSGS) during pregnancy presents distinct clinical challenges. As pregnancy is a naturally dyspneic state, the development of iSGS may exacerbate respiratory symptoms and compromise the airway—potentially impacting pregnancy and delivery decisions. This study characterizes surgical management strategies and outcomes in pregnant patients with symptomatic iSGS. Methods We conducted the largest known multi‐institutional retrospective review of pregnant patients who underwent endoscopic intervention for iSGS. Demographics, procedural details, anesthesia and medication use, and maternal and neonatal outcomes were analyzed. Results Twelve patients underwent 15 endoscopic procedures during pregnancy: 9 laser wedge excisions (8 CO 2 laser and 1 coblator) and 6 balloon dilations. Three additional procedures in different patients occurred postpartum (2–11 months after delivery). Higher‐risk pregnancies included two twin gestations, one patient with multiple surgeries during two different pregnancies, and two patients over age 35. Most interventions (87%) occurred in the second trimester. Fetal monitoring was performed preoperatively and postoperatively. Fentanyl and propofol were used in 88% and 94% of cases, respectively; rocuronium was the most common neuromuscular blocker (70%). One patient underwent balloon dilation via flexible bronchoscopy without anesthesia. Jet ventilation was used in 53% of cases, and Size C Kleinsasser laryngoscopes in 47%. Median procedure times were 75, 19, and 18 min for laser wedge excision, balloon dilation, and coblation, respectively. Most patients delivered full‐term with no surgical or postpartum complications. Conclusions Endoscopic intervention for iSGS during pregnancy appears safe and effective, even in high‐risk cases. These findings support individualized airway management and inform future practice. Level of Evidence 4.

Introduction Bronchoscopic lung volume reduction with endobronchial valves (EBV) is an effective procedure for patient with severe emphysema to improve lung function, exercise tolerance, dyspnoea and quality of life. Optimisation of patient and treatment lobe selection is essential for successful EBV outcomes. While clinical selection criteria are rigorous, many centres use a multidisciplinary team and rely on previous clinical experience for the selection process. To aid objective clinical decision making, we present a mathematical model to facilitate patient and target lobe selection. Methods A multidisciplinary team reviewed quantitative high-resolution computed tomography (HRCT) analysis from 119 patients to select candidates for EBV and to select a treatment lobe. Two logistic regression models, (1) candidacy for EBV placement and (2) target-lobe selection, were developed based on the normalised distributions of the four quantitative HRCT variables (fissure completeness score, per cent of voxel density with HU < −910 and HU < −950, and lobar volumes) across all five lung lobes. An external cohort of 50 patients (25 candidates and 25 non-candidates) was used to validate the prediction model. Results Performance measures of the training cohort demonstrated an area under the curve (AUC) of 0.91, accuracy of 81%, sensitivity of 93% and specificity of 78% compared with the multidisciplinary teams’ target lobe selection. The validation cohort demonstrated an AUC of 0.89, accuracy of 84%, sensitivity of 88% and specificity of 83% compared with the multidisciplinary team decision making. Conclusions Endobronchial valve lung volume reduction remains a potent palliative measure to improve quality of life in patients with hyperinflated emphysema. Our model for target lobe selection harnesses the multidisciplinary experience at a tertiary care centre to objectively select candidates and target lobes to assist clinicians’ decision making. Future studies investigating prediction of lobar collapse and functional improvement after target lobe selection using our model are needed.

ABSTRACTObjectiveThere is currently not a marker of disease severity in idiopathic subglottic stenosis (iSGS). Our objective was to characterize iSGS patients' disease severity using endoscopic surgery rates.MethodsThis was a two‐center retrospective analysis of iSGS patients with a minimum of 4 years of follow up following an initial endoscopic procedure (laser wedge excision (LWE) or endoscopic dilation (ED)). Disease severity was classified into Groups A–C, based on whether patients had fewer (Group A), the same number (Group B), or more surgeries (Group C) in years 3–5 compared to years 1 and 2. Disease severity proportions were compared across institutions using chi‐square analysis. Nonparametric testing compared clinical characteristics such as age, BMI, and GERD across severity groups.ResultsThere were 104 patients from institution 1 and 53 patients from institution 2 that were all female and predominantly Caucasian. Both institutions had clinically and statistically similar proportions of patients in Group A (64% vs. 62%), Group B (20% vs. 19%), and Group C (16% vs. 19%) disease (p > 0.05). No clinical characteristic (e.g., age, sex, race, BMI, GERD) was associated with disease severity.ConclusionAcross tertiary care institutions there is a consistent proportion of iSGS patients who either demonstrate nonrecurrent/decelerating (Group A), stable but persistent (Group B), or rapidly recurring disease (Group C). Two‐year surgery rates appear to be an important timepoint for providing expectations to patients on the likelihood of possessing severe disease.Level of Evidence4

Abstract Rational: Talc pleurodesis is an effective intervention for preventing recurrent pleural effusions and pneumothoraces, particularly in non-surgical candidates. Due to its efficacy and safety, it is recommended as the most effective sclerosant for pleurodesis. However, in some cases, the initial pleurodesis fails, necessitating a repeat procedure. The efficacy of repeat talc pleurodesis after an initial failure is an area that requires further exploration. This study explores the safety and efficacy of repeat talc pleurodesis among patients who did not respond to the initial intervention. Methods: This retrospective study analyzed hospitalized patients who underwent 4g talc slurry pleurodesis from 2019 to 2024, focusing on demographics, comorbidities, initial pleurodesis failure, and recurrence rates. Pleurodesis failure was identified by lung sliding, recurrent effusion, or pneumothorax during the same hospitalization. The primary outcome was recurrence post-discharge, assessed by pleural effusion or pneumothorax within 180 days post-repeat pleurodesis. Results: This study included 94 patients (52.1% male, 47.9% female) with a mean age of 67.6. Among them, 79 (84%) received a single 4g dose of talc, while 15 (16%) received multiple 4g talc doses for initial pleurodesis. Recurrence occurred in 20 (25.3%) of the single-dose group and 1 (6.7%) of the multiple-dose group within 180 days, though the difference was not statistically significant (p=0.112). Recurrence-free rates were 93.6% at 30 days, 85.1% at 90 days, and 77.7% at 180 days. Of the 20 patients with recurrence after a single 4g dose of talc, 8 (40%) underwent repeat pleurodesis, with only one recurrence requiring surgical intervention. Additionally, there was no recurrence after repeat talc pleurodesis in the one patient with recurrence after receiving multiple 4g talc doses for initial pleurodesis. No associations were found between recurrence rates and factors like gender (p=0.213) or comorbidities (emphysema, COPD, lung malignancy). Chest pain was a common complaint, but no cases of respiratory distress were reported post-pleurodesis. Conclusion: The efficacy of initial talc pleurodesis (77.7%-93.6%) in this cohort aligns with existing literature. Multiple-dose talc pleurodesis effectively prevented recurrence in 93.3% of patients, with no reported respiratory distress. Additionally, repeat talc pleurodesis was successful in 87.5% of those with recurrence after an initial single 4g dose. These findings support multiple-dose talc pleurodesis and repeat talc pleurodesis as safe and effective options for preventing recurrence post-initial failure and post-repeat talc pleurodesis, respectively. Although no significant recurrence predictors were identified, future research could focus on patient-specific factors to enhance treatment selection and optimize outcomes.

Abstract Rationale: Airway-stenosing disease is a significant clinical problem in multiple populations. While the immediate endoscopic and clinical response to bronchoscopic interventions are high, rates of clinically significant recurrence are elevated, and often require multiple and frequent reinterventions. Newer strategies to prevent recurrence of central and proximal airway stenosis are needed. Methods: Retrospective review of bronchoscopic balloon bronchoplasties performed at the Mayo Clinic utilizing paclitaxel coated balloons (PCB) in 2023-2024 for recurrent airway stenosis. IN.PACT Admiral and AV balloons (sizes 5-12 mm, 3.5 mcg/mm2 paclitaxel dose) were used with an inflation time of 2-3 minutes. Procedural success was defined as &lt;50% airway stenosis or resolution of the procedural indication. Reintervention was considered only if a therapeutic bronchoscopy was subsequently required to address the same lesion treated with PCB. Only patients with follow-ups &gt;90 days were included in the reintervention inter-procedural time analysis. Results: Thirty-three procedures were performed in 18 patients. Seventeen (51%) for lung transplantation-associated stenosis (29% anastomotic/perianastomotic, 76% lobar and segmental stenoses), 8 (24%) for granulomatous polyangiitis-associated stenosis, 3 for postintubation tracheal stenosis and 2 for chemical/pill injury. Eighteen cases (54%) utilized an additional dilation modality (12 non-coated balloon dilation, 4 rigid dilation), 5 spray cryotherapy, 6 other ablative therapies (4 CO2-laser, 2 electrocautery cuts), and 6 received an airway stent during the same procedure. 57% percent of interventions occurred in the lobar, 27% mainstem/bronchus intermedius, 9% tracheal, 7% segmental airways. Thirty-one (93%) cases had a satisfactory initial endoscopic result. The median number of bronchoscopic therapeutic interventions required before the use pf PCB was 5 (IQR 2.5-11.5), which significantly decreased to 0.1 (IQR 0-1, range 0-9) after PCB (p &lt;0.001). The reintervention-free survival significantly increased after PCB dilation from a median 35 days (IQR 28.7-80.5) to 132 days (IQR 64-197; p=0.004). Twenty-one cases required subsequent bronchoscopies, sixteen (76%) of which demonstrated improvement in lesion severity when compared to the results of prior interventions. Only 16 (48%) required therapeutically addressing the same lesion. Only 2 minor complications occurred (6%, self-limited bleeding and unplanned admission), none related to paclitaxel use. Six-month mortality was 3% from an unrelated cause. Conclusions: The locoregional antiproliferative effects of paclitaxel show promise in preventing recurrence, minimizing the need for repeat procedures, and extending intervals between interventions in patients with recurrent, predominantly benign airway stenosis. Its use is feasible, safe, and future research is warranted, particularly comparing PCB with the currently available strategies.