Epidemiology and Survival of Malignant Central Airway Obstruction in Lung Cancer Identified on Cross-Sectional Imaging.

BACKGROUND: The prevalence of malignant central airway obstruction at diagnosis and its 5-year incidence are largely unknown, as are basic epidemiological data pertaining to this serious condition. To address these data limitations, we retrospectively collected data from the cohort of patients diagnosed with lung cancer at our institution in 2015 and followed cohort patients 5 years forward, until 2020. METHODS: We reviewed index PET/CT or CT scans at the time of lung cancer diagnosis to identify the presence, subtype, and severity of malignant central airway obstruction as well as progression/development over the next 5 years. RESULTS: The prevalence of malignant central airway obstruction affecting the airway lumen by 25% or greater was 17%, and its 5-year incidence of development was 8.2%. Notable associations from the multivariate analysis included a younger age and a stepwise increase in obstruction with increasing stage of disease. Squamous cell carcinoma and small-cell lung cancer were the 2 histologic subtypes with the strongest association with obstruction. The presence of malignant central airway obstruction either at time of diagnosis or on follow-up imaging was associated with significantly shortened survival (multivariate Cox proportional HR for MCAO=1.702, P<0.001). CONCLUSION: This study provides the first systematic characterization of fundamental epidemiological data on malignant central airway obstructions at a tertiary cancer center in the United States. This data is important to inform research directions and funding efforts of this serious complication. It also serves as a baseline value against which to compare for future studies.

Correlation of Bronchoscopy and CT in Characterizing Malignant Central Airway Obstruction.

BACKGROUND: Malignant Central Airway Obstruction (MCAO) presents a significant challenge in lung cancer management, with notable morbidity and mortality implications. While bronchoscopy is the established diagnostic standard for confirming MCAO and assessing obstruction subtype (intrinsic, extrinsic, mixed) and severity, Computed Tomography (CT) serves as an initial screening tool. However, the extent of agreement between CT and bronchoscopy findings for MCAO remains unclear. METHODS: To assess the correlation between bronchoscopy and CT, we conducted a retrospective review of 108 patients at Roswell Park Comprehensive Cancer Center, analyzing CT and bronchoscopy results to document MCAO presence, severity, and subtype. RESULTS: CT correctly identified MCAO in 99% of cases (107/108). Agreement regarding obstruction subtype (80.8%, Cohen's κ = 0.683, p < 0.001), and severity (65%, Quadratic κ = 0.657, p < 0.001) was moderate. CT tended to equally overestimate (7/19) and underestimate (7/19) the degree of obstruction. CT was also poor in identifying mucosal involvement in mixed MCAO. CONCLUSIONS: CT demonstrates reasonable agreement with bronchoscopy in detecting obstruction. Nevertheless, when CT indicates a positive finding for MCAO, it is advisable to conduct bronchoscopy. This is because CT lacks reliability in determining the severity of obstruction and identifying the mucosal component of mixed disease.

The Use of a Fabricated Endotracheal Tube During an Acute Massive Pulmonary Hemorrhage: A Case Report.

A massive pulmonary hemorrhage is an emergency that can lead to airway compromise and cardiovascular collapse. The goals of airway management are to isolate and protect the nonbleeding lung while providing a route for interventions to diagnose and control the bleeding site. We present a case of an adult male with a lung mass who underwent a bronchoscopy and cryobiopsy that was complicated by a massive pulmonary hemorrhage. We report the successful use of an elongated fabricated end-to-end endotracheal tube to manage his airway during this time-critical situation.

Immunoprofiling bronchoalveolar lavage cells reveals multifaceted smoking-associated immune dysfunction.

Background: Bronchoalveolar lavage (BAL) is an underutilised tool in the search for pulmonary disease biomarkers. While leukocytes with effector and suppressor function play important roles in airway immunity and tumours, it remains unclear if frequencies and phenotypes of BAL leukocytes can be useful parameters in lung cancer studies and clinical trials. We therefore explored the utility of BAL leukocytes as a source of biomarkers interrogating the impact of smoking, a major lung cancer risk determinant, on pulmonary immunity. Methods: In this "test case" observational study, BAL samples from 119 donors undergoing lung cancer screening and biopsy procedures were evaluated by conventional and spectral flow cytometry to exemplify the comprehensive immune analyses possible with this biospecimen. Proportions of major leukocyte populations and phenotypic markers levels were found. Multivariate linear rank sum analysis considering age, sex, cancer diagnosis and smoking status was performed. Results: Significantly increased frequencies of myeloid-derived suppressor cells and PD-L1-expressing macrophages were found in current and former smokers compared to never-smokers. While cytotoxic CD8 T-cells and conventional CD4 helper T-cell frequencies were significantly reduced in current and former smokers, expression of immune checkpoints PD-1 and LAG-3 as well as Tregs proportions were increased. Lastly, the cellularity, viability and stability of several immune readouts under cryostorage suggested BAL samples are useful for correlative end-points in clinical trials. Conclusions: Smoking is associated with heightened markers of immune dysfunction, readily assayable in BAL, that may reflect a permissive environment for cancer development and progression in the airway.

Computational Optimization of Irradiance and Fluence for Interstitial Photodynamic Therapy Treatment of Patients with Malignant Central Airway Obstruction.

There are no effective treatments for patients with extrinsic malignant central airway obstruction (MCAO). In a recent clinical study, we demonstrated that interstitial photodynamic therapy (I-PDT) is a safe and potentially effective treatment for patients with extrinsic MCAO. In previous preclinical studies, we reported that a minimum light irradiance and fluence should be maintained within a significant volume of the target tumor to obtain an effective PDT response. In this paper, we present a computational approach to personalized treatment planning of light delivery in I-PDT that simultaneously optimizes the delivered irradiance and fluence using finite element method (FEM) solvers of either Comsol Multiphysics® or Dosie™ for light propagation. The FEM simulations were validated with light dosimetry measurements in a solid phantom with tissue-like optical properties. The agreement between the treatment plans generated by two FEMs was tested using typical imaging data from four patients with extrinsic MCAO treated with I-PDT. The concordance correlation coefficient (CCC) and its 95% confidence interval (95% CI) were used to test the agreement between the simulation results and measurements, and between the two FEMs treatment plans. Dosie with CCC = 0.994 (95% CI, 0.953-0.996) and Comsol with CCC = 0.999 (95% CI, 0.985-0.999) showed excellent agreement with light measurements in the phantom. The CCC analysis showed very good agreement between Comsol and Dosie treatment plans for irradiance (95% CI, CCC: 0.996-0.999) and fluence (95% CI, CCC: 0.916-0.987) in using patients' data. In previous preclinical work, we demonstrated that effective I-PDT is associated with a computed light dose of ≥45 J/cm2 when the irradiance is ≥8.6 mW/cm2 (i.e., the effective rate-based light dose). In this paper, we show how to use Comsol and Dosie packages to optimize rate-based light dose, and we present Dosie's newly developed domination sub-maps method to improve the planning of the delivery of the effective rate-based light dose. We conclude that image-based treatment planning using Comsol or Dosie FEM-solvers is a valid approach to guide the light dosimetry in I-PDT of patients with MCAO.

Management of malignancy-induced, life-threatening hypoxemic respiratory failure using a self-expanding Y stent.

We present the case of a young woman transferred to our center with acute hypoxic respiratory failure due to an obstructing subcarinal mass. We review the management and rationale of this respiratory failure at different stages of her hospital course. We describe the approach and rationale in both the intensive care unit as well as the bronchoscopy suite. Finally, we discuss how the use of a novel hybrid Y stent effectively palliated her symptoms.

First-In-Human Computer-Optimized Endobronchial Ultrasound-Guided Interstitial Photodynamic Therapy for Patients With Extrabronchial or Endobronchial Obstructing Malignancies.

Objective: Patients with inoperable extrabronchial or endobronchial tumors who are not candidates for curative radiotherapy have dire prognoses with no effective long-term treatment options. To reveal that our computer-optimized interstitial photodynamic therapy (I-PDT) is safe and potentially effective in the treatment of patients with inoperable extra or endobronchial malignancies inducing central airway obstructions. Methods: High-spatial resolution computer simulations were used to personalize the light dose rate and dose for each tumor. Endobronchial ultrasound with a transbronchial needle was used to place the optical fibers within the tumor according to an individualized plan. The primary and secondary end points were safety and overall survival, respectively. An exploratory end point evaluated changes in immune markers. Results: Eight patients received I-PDT with planning, and five of these received additional external beam PDT. Two additional patients received external beam PDT. The treatment was declared safe. Three of 10 patients are alive at 26.3, 12, and 8.3 months, respectively, after I-PDT. The treatments were able to deliver a prescribed light dose rate and dose to 87% to 100% and 18% to 92% of the tumor volumes, respectively. A marked increase in the proportion of monocytic myeloid-derived suppressor cells expressing programmed death-ligand 1 was measured in four of seven patients. Conclusions: Image-guided light dosimetry for I-PDT with linear endobronchial ultrasound transbronchial needle is safe and potentially beneficial in increasing overall survival of patients. I-PDT has a positive effect on the immune response including an increase in the proportion of programmed death-ligand 1-expressing monocytic myeloid-derived suppressor cells.

Cone Beam CT Guidance Improves Transbronchial Lung Cryobiopsy Safety.

INTRODUCTION: Determining the cause of diffuse parenchymal lung disease (DPLD) is challenging. While surgical lung biopsy has been the standard approach, transbronchial lung cryobiopsy (TBLC) represents a minimally invasive alternative with an acceptable safety profile and reasonable accuracy. In this study, we prospectively assessed whether the use of cone beam CT (CBCT) coupled with a novel bronchoscope holder and prophylactic administration of vasoconstricting medications decreases potential complications and improves diagnostic accuracy when performing TBLC. METHODS: 33 patients presenting for evaluation of newly diagnosed DPLD were enrolled. Demographic data, pulmonary function values, chest imaging pattern, procedural information, and diagnosis were recorded. RESULTS: Mean patient age was 67, with the majority Caucasian (n = 26, 79%) and male (n = 20, 61%). Mean pulmonary function values revealed restrictive lung disease (76 ± 14% predicted) and diffusing capacity impairment (52 ± 16%). A non-usual interstitial pneumonia imaging pattern was commonly seen (n = 20, 61%). CBCT guided TBLC was performed in one lobe (n = 29, 88%) or two lobes (n = 4, 12%) with mean probe-to-pleura distance of 4.2 ± 1.3 mm. No peri or post procedural complications occurred. 32 patients (97%) received a histological diagnosis with a final multidisciplinary conference diagnosis possible for 32 (97%). CONCLUSION: CBCT guided TBLC coupled with a novel articulating scope holder and prophylactic phenylephrine administration has the potential to increase safety and diagnostic yield for patients with newly identified DPLD. Future studies comparing different aspects of this approach in isolation and with other modalities have the potential to refine this procedure to improve patient care.

A retrospective observational study of benign anthracotic lymphadenitis and its association with PET avid lymph nodes in patients undergoing cancer evaluation.

BACKGROUND: Accurate staging of newly diagnosed or recurrent malignancy is essential for effective treatment. An important first step in staging involves the use of PET/CT to identify areas of FDG avidity. PET/CT however has limitations, including false positive FDG uptake from benign causes. In this paper we characterize an uncommon yet clinically important cause of false positive PET/CTs, that of benign anthracotic lymphadenitis (BAL). We examine the clinical, radiographic and histologic characteristics of BAL in patients referred for endobronchial ultrasound (EBUS) guided biopsies and discuss its context in relation to existing literature. METHODS: We performed a retrospective observational case series of 20 patients who were referred for EBUS guided biopsies of PET positive mediastinal and hilar lymph nodes during the work-up or treatment of suspected malignancy. RESULTS: To be included, all patients received PET imaging as well as an EBUS guided biopsy of FDG avid lymph nodes which demonstrated anthracotic pigment as the only histologic abnormality. The key findings were that 90% of patients in this cohort were born outside of the US, 90% had bilateral FDG avid lymph nodes with an average standardized uptake value (SUV) of 7.9±2.2. Most patients, based on their history, had a likely exposure to biomass fuel or urban pollution. CONCLUSIONS: BAL may be an underrecognized cause for PET positive lymph nodes in patients undergoing work-up for malignancy. These findings support the importance of sampling mediastinal and hilar lymph nodes even when SUVs are highly suggestive of malignancy.

Endobronchial Leiomyoma: A case report with cryoprobe extraction and review of literature.

Large airway tumors are uncommon, accounting for about 0.6% of all pulmonary tumors [[1], [2], [3]]. The majority of these tumors (80-90%) are malignant, represented primarily by squamous cell carcinoma and adenoid cystic carcinoma [2,4]. Benign central airway tumors are less common and are generally comprised of hamartomas and papillomas. Tracheobronchial leiomyomas are exceedingly rare, representing only about 0.6% of all benign lung neoplasms [3]. We report here on a case of primary endobronchial leiomyoma without uterine involvement treated successfully with cryoresection with excellent outcome.

QA project: Hemodynamic safety of endobronchial administration of phenylephrine for control of airway bleeding by bronchoscopy.

BACKGROUND: Phenylephrine has been administered endobronchially for airway bleeding during bronchoscopy as an alternative to epinephrine. Topical phenylephrine, often used in nasal surgery as a vasoconstrictor agent has been linked to cardiovascular morbidity. OBJECTIVE: To evaluate the safety of bronchoscopic instillation of phenylephrine during bronchoscopy. METHODS: We retrospectively reviewed patients who received endobronchial phenylephrine in our endoscopy suite. We compared the changes in blood pressure and heart rate before and after endobronchial phenylephrine administration. The safety of endobronchial phenylephrine was assessed with regards to the changes in hemodynamics and acute cardiovascular event, and 30-day mortality. Acute cardiovascular complications included acute coronary syndrome, aortic dissection, tachyarrhythmias, pulmonary edema and stroke. RESULTS: We identified 30 patients who received endobronchial phenylephrine 100mcg/ml with a mean total volume of 6.5 ± 10.6 ml. They were given mainly for balloon dilation and cryobiopsy procedure (96.7%). On excluding patients who received concurrent IV pressor, there was a statistically significant increase of mean arterial pressure (MAP) by 12 ± 21 mmHg, p = 0.01 within 30 min of endobronchial phenylephrine compared to procedure day MAP baseline. There was 27% of patients with more than 20% increase in their MAP but none of the patients had MAP more than 140 nor the occurrence of acute cardiovascular event. There was no significant change in the patients' heart rate following endobronchial phenylephrine. CONCLUSION: In our review, endobronchial phenylephrine with dose comparable to IV administration can cause significant raise in MAP but their absolute levels did not go beyond 180/120 mmHg nor resulted in acute cardiovascular complications.