The Effect of Definitions and Cancer Prevalence on Diagnostic Yield Estimates of Bronchoscopy: A Simulation-based Analysis.

Rationale: Studies of bronchoscopy have reported diagnostic yield (DY) using different calculation methods, which has hindered comparisons across studies. Objectives: To quantify the effect of the variability of four methods on DY estimates of bronchoscopy. Methods: We performed a simulation-based analysis of patients undergoing bronchoscopy using variations around base case assumptions for cancer prevalence (60%), distribution of nonmalignant findings, and degree of follow-up information at a fixed sensitivity of bronchoscopy for malignancy (80%). We calculated DY, the rate of true positives and true negatives (TNs), using four methods. Method 1 considered malignant and specific benign findings at index bronchoscopy as true positives and TNs, respectively. Method 2 included nonspecific benign findings as TNs. Method 3 considered nonspecific benign findings cases as TNs only if follow-up confirmed benign disease. Method 4 counted all cases with a nonmalignant diagnosis as TNs if follow-up confirmed benign disease. A scenario analysis and probabilistic sensitivity analysis were conducted to demonstrate the effect of parameter estimates on DY. A change in DY of >10% was considered clinically meaningful. Results: Across all pairwise comparisons of the four methods, a DY difference of >10% was observed in 76.7% of cases (45,992 of 60,000 comparisons). Method 4 resulted in DY estimates that were >10% higher than estimates made with other methods in >90% of scenarios. Variation in cancer prevalence had a large effect on DY. Conclusions: Across a wide range of clinical scenarios, the categorization of nonmalignant findings at index bronchoscopy and cancer prevalence had the largest impact on DY. The large variability in DY estimates across the four methods limits the interpretation of bronchoscopy studies and warrants standardization.

Stereotactic body radiation therapy and thermal ablation for treatment of NSCLC: A systematic literature review and meta-analysis.

RATIONALE: Stereotactic body radiation therapy (SBRT) is the standard of care for inoperable early stage non-small cell lung cancer (NSCLC). Use of image guided thermal ablation (IGTA; including microwave ablation [MWA] and radiofrequency ablation [RFA]) has increased in NSCLC, however there are no studies comparing all three. OBJECTIVE: To compare the efficacy of IGTA (including MWA and RFA) and SBRT for the treatment of NSCLC. METHODS: Published literature databases were systematically searched for studies assessing MWA, RFA, or SBRT. Local tumor progression (LTP), disease-free survival (DFS), and overall survival (OS) were assessed with single-arm pooled analyses and meta-regressions in NSCLC patients and a stage IA subgroup. Study quality was assessed with a modified methodological index for non-randomized studies (MINORS) tool. RESULTS: Forty IGTA study-arms (2,691 patients) and 215 SBRT study-arms (54,789 patients) were identified. LTP was lowest after SBRT at one and two years in single-arm pooled analyses (4% and 9% vs. 11% and 18%) and at one year in meta-regressions when compared to IGTA (OR = 0.2, 95%CI = 0.07-0.63). MWA patients had the highest DFS of all treatments in single-arm pooled analyses. In meta-regressions at two and three-years, DFS was significantly lower for RFA compared to MWA (OR = 0.26, 95%CI = 0.12-0.58; OR = 0.33, 95%CI = 0.16-0.66, respectively). OS was similar across modalities, timepoints, and analyses. Older age, male patients, larger tumors, retrospective studies, and non-Asian study region were also predictors of worse clinical outcomes. In high-quality studies (MINORS score ≥ 7), MWA patients had better clinical outcomes than the overall analysis. Stage IA MWA patients had lower LTP, higher OS, and generally lower DFS, compared to the main analysis of all NSCLC patients. CONCLUSIONS: NSCLC patients had comparable outcomes after SBRT and MWA, which were better than those with RFA.

Diagnostic outcomes of robotic-assisted bronchoscopy for pulmonary lesions in a real-world multicenter community setting.

BACKGROUND: Robot-assisted bronchoscopy (RAB) is among the newest bronchoscopic technologies, allowing improved visualization and access for small and hard-to-reach nodules. RAB studies have primarily been conducted at academic centers, limiting the generalizability of results to the broader real-world setting, while variability in diagnostic yield definitions has impaired the validity of cross-study comparisons. The objective of this study was to determine the diagnostic yield and sensitivity for malignancy of RAB in patients with pulmonary lesions in a community setting and explore the impact of different definitions on diagnostic yield estimates. METHODS: Data were collected retrospectively from medical records of patients ≥ 21 years who underwent bronchoscopy with the Monarch® Platform (Auris Health, Inc., Redwood City, CA) for biopsy of pulmonary lesions at three US community hospitals between January 2019 and March 2020. Diagnostic yield was calculated at the index RAB and using 12-month follow-up data. At index, all malignant and benign (specific and non-specific) diagnoses were considered diagnostic. After 12 months, benign non-specific cases were considered diagnostic only when follow-up data corroborated the benign result. An alternative definition at index classified benign non-specific results as non-diagnostic, while an alternative 12-month definition categorized index non-diagnostic cases as diagnostic if no malignancy was diagnosed during follow-up. RESULTS: The study included 264 patients. Median lesion size was 19.3 mm, 58.9% were peripherally located, and 30.1% had a bronchus sign. Samples were obtained via Monarch in 99.6% of patients. Pathology led to a malignant diagnosis in 115 patients (43.6%), a benign diagnosis in 110 (41.7%), and 39 (14.8%) non-diagnostic cases. Index diagnostic yield was 85.2% (95% CI: [80.9%, 89.5%]) and the 12-month diagnostic yield was 79.4% (95% CI: [74.4%, 84.3%]). Alternative definitions resulted in diagnostic yield estimates of 58.7% (95% CI: [52.8%, 64.7%]) at index and 89.0% (95% CI: [85.1%, 92.8%]) at 12 months. Sensitivity for malignancy was 79.3% (95% CI: [72.7%, 85.9%]) and cancer prevalence was 58.0% after 12 months. CONCLUSIONS: RAB demonstrated a high diagnostic yield in the largest study to date, despite representing a real-world community population with a relatively low prevalence of cancer. Alternative definitions had a considerable impact on diagnostic yield estimates.

Detecting Ground Glass Opacity Features in Patients With Lung Cancer: Automated Extraction and Longitudinal Analysis via Deep Learning-Based Natural Language Processing.

BACKGROUND: Ground-glass opacities (GGOs) appearing in computed tomography (CT) scans may indicate potential lung malignancy. Proper management of GGOs based on their features can prevent the development of lung cancer. Electronic health records are rich sources of information on GGO nodules and their granular features, but most of the valuable information is embedded in unstructured clinical notes. OBJECTIVE: We aimed to develop, test, and validate a deep learning-based natural language processing (NLP) tool that automatically extracts GGO features to inform the longitudinal trajectory of GGO status from large-scale radiology notes. METHODS: We developed a bidirectional long short-term memory with a conditional random field-based deep-learning NLP pipeline to extract GGO and granular features of GGO retrospectively from radiology notes of 13,216 lung cancer patients. We evaluated the pipeline with quality assessments and analyzed cohort characterization of the distribution of nodule features longitudinally to assess changes in size and solidity over time. RESULTS: Our NLP pipeline built on the GGO ontology we developed achieved between 95% and 100% precision, 89% and 100% recall, and 92% and 100% F1-scores on different GGO features. We deployed this GGO NLP model to extract and structure comprehensive characteristics of GGOs from 29,496 radiology notes of 4521 lung cancer patients. Longitudinal analysis revealed that size increased in 16.8% (240/1424) of patients, decreased in 14.6% (208/1424), and remained unchanged in 68.5% (976/1424) in their last note compared to the first note. Among 1127 patients who had longitudinal radiology notes of GGO status, 815 (72.3%) were reported to have stable status, and 259 (23%) had increased/progressed status in the subsequent notes. CONCLUSIONS: Our deep learning-based NLP pipeline can automatically extract granular GGO features at scale from electronic health records when this information is documented in radiology notes and help inform the natural history of GGO. This will open the way for a new paradigm in lung cancer prevention and early detection.

Evaluation of Safety and Short-term Outcomes of Therapeutic Rigid Bronchoscopy Using Total Intravenous Anesthesia and Spontaneous Assisted Ventilation.

BACKGROUND: There is a paucity of published data regarding the optimal type of anesthesia and ventilation strategies during rigid bronchoscopy. OBJECTIVE: The aim of our study is to report the procedural and anesthesia-related complications with rigid bronchoscopy using total intravenous anesthesia and spontaneous assisted ventilation. METHODS: A retrospective review of patients undergoing therapeutic rigid bronchoscopy at the University of Chicago between October 2012 and December 2014 was performed. Data were recorded relating to patients' demographics, comorbidities, type of anesthesia, need for neuromuscular blockade (NMB), intraoperative hypoxemia, hypotension, perioperative adverse events, and mortality. RESULTS: Fifty-five patients underwent 79 rigid bronchoscopy procedures; 90% were performed for malignant disease and 90% of patients had an American Society of Anesthesiologists (ASA) class III or IV. The majority (76%) did not require use of NMB. The most common adverse events were intraoperative hypoxemia (67%) and hypotension (77%). Major bleeding and postoperative respiratory failure occurred in 3.8 and 5.1% of procedures, respectively. There was no intraoperative mortality or cardiac dysrhythmias. The 30-day mortality was 7.6% and was associated with older age, inpatient status, congestive heart failure, home oxygen use, and procedural duration. Intraoperative hypoxemia, hypotension, and ASA class were not associated with 30-day mortality. The majority (94%) of patients were discharged home. The use of NMB did not impact outcomes. CONCLUSIONS: This study suggests that therapeutic rigid bronchoscopy can be safely performed with total intravenous anesthesia and spontaneous assisted ventilation in patients with central airway obstruction, significant comorbidities, and a high ASA class. The only significant modifiable variable predicting the 30-day mortality was the duration of the procedure.

Tunneled Pleural Catheter: Treatment for Recurrent Pleural Effusion.

Recurrent pleural effusion is a symptom of several end-stage diseases and is associated with limited life expectancy. Patients with this condition have disabling symptoms resulting in reduced quality of life and often receive inconsistent treatment due to delayed recognition of pleural effusion, repeat procedures, and lengthy hospitalizations. Placement of a tunneled pleural catheter allows the patient to manage his or her symptoms at home, yet this treatment remains underused because of provider misconceptions and unfamiliarity with the intervention. This article provides an overview of the indications for placement of a tunneled pleural catheter, possible complications, and management strategies, and introduces evidence-based clinical decision support tools to enhance provider knowledge. In addition, the article describes the implementation and evaluation of a performance improvement initiative on the use of tunneled pleural catheters in a multifaceted health care system.

Management of Persistent Air Leaks.

Alveolar-pleural fistulas causing persistent air leaks (PALs) are associated with prolonged hospital stays and high morbidity. Prior guidelines recommend surgical repair as the gold standard for treatment, albeit it is a solution with limited success. In patients who have recently undergone thoracic surgery or in whom surgery would be contraindicated based on the severity of illness, there has been a lack of treatment options. This review describes a brief history of treatment guidelines for PALs. In the past 20 years, newer and less invasive treatment options have been developed. Aside from supportive care, the literature includes anecdotal successful reports using fibrin sealants, ethanol injection, metal coils, and Watanabe spigots. More recently, larger studies have demonstrated success with chemical pleurodesis, autologous blood patch pleurodesis, and endobronchial valves. This manuscript describes these treatment options in detail, including postprocedural adverse events. Further research, including randomized controlled trials with comparison of these options, are needed, as is long-term follow-up for these interventions.

Advances in Bronchial Thermoplasty.

Bronchial thermoplasty (BT) is a therapeutic intervention that delivers targeted thermal energy to the airway walls with the goal of ablating the smooth muscle in patients with severe persistent asthma. Since the publication of the original preclinical studies, three large randomized clinical trials evaluating its impact on asthma control have been performed. These trials have shown improvements in asthma-related quality of life and a reduction in asthma exacerbations following treatment with BT. However, there remains significant controversy regarding the true efficacy of BT and the interpretation of these studies, particularly the Asthma Intervention Research 2 trial. In this article, we will discuss these controversies and present the latest evidence on the use of BT in asthma, specifically the 5-year longitudinal evaluation of patients. In addition, we will discuss new insights into the histopathologic changes that occur in the airways following BT, as well as the feasibility of performing the procedure in patients with very severe asthma. We also will discuss the ongoing translational and clinical investigations regarding the underlying mechanism of action and methods to improve patient selection for this procedure.

Central Airway Obstruction: Benign Strictures, Tracheobronchomalacia, and Malignancy-related Obstruction.

The purpose of this article is to provide an update on methods for palliating symptoms in patients with histologically benign and malignant central airway obstruction. We review the published literature within the past decade on postintubation, posttracheostomy, and TB- and transplant-related airway strictures; tracheobronchomalacia; and malignant airway obstruction. We review terminology, classification systems, and parameters that impact treatment decisions. The focus is on how airway stent insertion fits into the best algorithm of care. Several case series and cohort studies demonstrate that airway stents improve dyspnea, lung function, and quality of life in patients with airway obstruction. Airway stenting, however, is associated with high rates of adverse events and should be used only when curative open surgical interventions are not feasible or are contraindicated.

Bronchial thermoplasty in asthma: current perspectives.

Bronchial thermoplasty (BT) is a novel therapy for patients with severe asthma. Using radio frequency thermal energy, it aims to reduce the airway smooth muscle mass. Several clinical trials have demonstrated improvements in asthma-related quality of life and a reduction in the number of exacerbations following treatment with BT. In addition, recent data has demonstrated the long-term safety of the procedure as well as sustained improvements in rates of asthma exacerbations, reduction in health care utilization, and improved quality of life. Further study is needed to elucidate the underlying mechanisms that result in these improvements. In addition, improved characterization of the asthma subphenotypes likely to exhibit the largest clinical benefit is a critical step in determining the precise role of BT in the management of severe asthma.

Toll-like receptor 1 polymorphisms and associated outcomes in sepsis after traumatic injury: a candidate gene association study.

OBJECTIVE: To determine whether single nucleotide polymorphisms (SNPs) in TLR1 are associated with mortality, specifically sepsis-associated mortality, in a traumatically injured population. BACKGROUND: Innate immune responses mediated by toll-like receptors (TLRs) induce early inflammatory responses to pathogen and damage-associated molecular patterns. Genetic variation in TLRs has been associated with susceptibility and outcomes in a number of infectious and noninfectious disease states. METHODS: Patients admitted to the trauma intensive care unit at a level 1 trauma center serving 4 states were enrolled and followed for development of infection, sepsis, and death. Genomic DNA was genotyped and logistic regression analysis was performed to determine associations between TLR1 SNPs and mortality. We further examined for associations between TLR1 SNPs and mortality in subgroups on the basis of the presence of sepsis and the type of sepsis-associated organism. RESULTS: We enrolled 1961 patients. TLR1-7202G (rs5743551) was associated with increased mortality after traumatic injury and this association was primarily observed in the subset of patients who developed sepsis [adjusted odds ratio (OR): 3.16; 95% confidence interval (CI): 1.43-6.97, P=0.004]. This association persisted after further restriction to gram-positive sepsis. TLR1(742A/G(Asn248Ser)) (rs4833095), a coding SNP in LD with TLR1-7202G, was also associated with mortality in gram-positive sepsis (adjusted OR: 4.16; 95% CI: 1.22-14.19, P=0.023). CONCLUSIONS: Genetic variation in TLR1 is associated with increased mortality in patients with sepsis after traumatic injury and may represent a novel marker of risk for death in critically injured patients.