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Background Two models, the Help with the Assessment of Adenopathy in Lung cancer (HAL) and Help with Oncologic Mediastinal Evaluation for Radiation (HOMER), were recently developed to estimate the probability of nodal disease in patients with non-small cell lung cancer (NSCLC) as determined by endobronchial ultrasound-transbronchial needle aspiration (EBUS-TBNA). The objective of this study was to prospectively externally validate both models at multiple centers. Research Question Are the HAL and HOMER models valid across multiple centers? Study Design and Methods This multicenter prospective observational cohort study enrolled consecutive patients with PET-CT clinical-radiographic stages T1-3, N0-3, M0 NSCLC undergoing EBUS-TBNA staging. HOMER was used to predict the probability of N0 vs N1 vs N2 or N3 (N2|3) disease, and HAL was used to predict the probability of N2|3 (vs N0 or N1) disease. Model discrimination was assessed using the area under the receiver operating characteristics curve (ROC-AUC), and calibration was assessed using the Brier score, calibration plots, and the Hosmer-Lemeshow test. Results Thirteen centers enrolled 1,799 patients. HAL and HOMER demonstrated good discrimination: HAL ROC-AUC = 0.873 (95%CI, 0.856-0.891) and HOMER ROC-AUC = 0.837 (95%CI, 0.814-0.859) for predicting N1 disease or higher (N1|2|3) and 0.876 (95%CI, 0.855-0.897) for predicting N2|3 disease. Brier scores were 0.117 and 0.349, respectively. Calibration plots demonstrated good calibration for both models. For HAL, the difference between forecast and observed probability of N2|3 disease was +0.012; for HOMER, the difference for N1|2|3 was −0.018 and for N2|3 was +0.002. The Hosmer-Lemeshow test was significant for both models (P = .034 and .002), indicating a small but statistically significant calibration error. Interpretation HAL and HOMER demonstrated good discrimination and calibration in multiple centers. Although calibration error was present, the magnitude of the error is small, such that the models are informative.

Atelectasis negatively influences peripheral bronchoscopy, increasing CT scan-body divergence, obscuring targets, and creating false-positive radial-probe endobronchial ultrasound (RP-EBUS) images.Can a ventilatory strategy reduce the incidence of atelectasis during bronchoscopy under general anesthesia?Randomized controlled study (1:1) in which patients undergoing bronchoscopy were randomized to receive standard ventilation (laryngeal mask airway, 100% FioSeventy-six patients were analyzed, 38 in each group. The proportion of patients with any atelectasis according to chest CT scan at time 2 was 84.2% (95% CI, 72.6%-95.8%) in the control group and 28.9% (95% CI, 15.4%-45.9%) in the VESPA group (P .0001). The proportion of patients with bilateral atelectasis at time 2 was 71.1% (95% CI, 56.6%-85.5%) in the control group and 7.9% (95% CI, 1.7%-21.4%) in the VESPA group (P .0001). At time 2, 3.84 ± 1.67 (mean ± SD) bronchial segments in the control group vs 1.21 ± 1.63 in the VESPA group were deemed atelectatic (P .0001). No differences were found in the rate of complications.VESPA significantly reduced the incidence of atelectasis, was well tolerated, and showed a sustained effect over time despite bronchoscopic nodal staging maneuvers. VESPA should be considered for bronchoscopy when atelectasis is to be avoided.ClinicalTrials.gov; No.: NCT04311723; URL: www.gov.

Rationale: When stereotactic ablative radiotherapy is an option for patients with non–small cell lung cancer (NSCLC), distinguishing between N0, N1, and N2 or N3 (N2|3) disease is important.Objecti...

Context.— Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is routinely used to evaluate mediastinal lymph nodes (LNs), especially for cancer staging. There are limited large studies evaluating the cytologic, radiologic, and clinical features of 18F-fluorodeoxy glucose positron emission tomography-computed tomography–positive (PET-CT+) LNs. Objective.— To compare cytologic, radiologic, and clinical features of PET-CT+, cytology-malignant (PET-CT+/Cyto+) and PET-CT+, cytology-benign (PET-CT+/Cyto−) LNs. Design.— The pathology database was searched for cases of mediastinal LNs obtained by EBUS-TBNA from January 1, 2015 to December 31, 2015. The cytologic, radiologic, and clinical features were collected for all PET-CT+ LNs. Results.— Of 2267 mediastinal LNs obtained by EBUS-TBNA during this period, 577 LNs met the criteria. Of the latter, 263 (46%) were PET-CT+/Cyto+ and 314 (54%) were PET-CT+/Cyto−. All of the patients with PET-CT+/Cyto+ results had a prior or concurrent diagnosis of malignancy as compared to 89% of patients with PET-CT+/Cyto− results. Of the 224 patients with PET-CT+/Cyto+ LNs, 177 (79%) had metastases from lung primary, 43 (19%) had metastases from nonlung primaries, and 7 (3%) had lymphoma. Average LN size was larger in the PET-CT+/Cyto+ group than in the PET-CT+/Cyto− group (14.6 mm versus 9.58 mm), and mean standardized uptake value in PET-CT+/Cyto+ LNs was higher than that of PET-CT+/Cyto− LNs (10.05 versus 5.99). Significant cytologic findings in PET-CT+/Cyto− cases were necrosis and granulomatous inflammation, including 3 cases with fungal organisms. Conclusions.— PET-CT positivity alone was nonspecific for malignancy and insufficient to guide management of patients with mediastinal adenopathy, but specificity could be improved when combined with LN size and standardized uptake value.

Lung cancer is the world's leading cause of cancer death. Screening for lung cancer by low-dose computed tomography improves mortality. Various modalities exist for diagnosis and staging. Treatment is determined by subtype and stage of cancer; there are several personalized therapies that did not exist just a few years ago. Caring for the patient with lung cancer is a complex task. This review provides a broad outline of this disease, helping clinicians identify such patients and familiarizing them with lung cancer care options, so they are better equipped to guide their patients along this challenging journey.

Background: Despite advances in bronchoscopy, its diagnostic yield for peripheral lung lesions continues to be suboptimal. Cone beam computed tomography (CBCT) could be utilized to corroborate the accuracy of our bronchoscopic navigation and hopefully increase its diagnostic yield. However, data on radiation exposure and feasibility of CBCT-guided bronchoscopy is scarce. Methods: Prospective pilot study of bronchoscopy for peripheral lung nodules under general anesthesia with thin/ultrathin bronchoscope, radial-probe endobronchial ultrasound (RP-EBUS), and CBCT. Main objective was to estimate radiation dose and secondary objective was the additional value of CBCT in terms of navigational and diagnostic yield. Results: A total of 20 patients were enrolled. Median lesion size was 2.1 (range, 1.1–3) cm and distance from pleura was 2.1 (range, 0–2.8) cm. “Bronchus sign” was present in 12 (60%) of the lesions. Totally, 12 lesions (60%) were invisible on fluoroscopy. CBCT identified atelectasis obscuring the target in 4 cases (20%). Eleven patients (55%) underwent 1 CBCT scan and 9 patients (45%) 2. The mean estimated effective dose (E) to patients resulting from CBCT ranged between 8.6 and 23 mSv, depending on utilized conversion factors. Both pre-CBCT navigation and diagnostic yield were 50%. Additional post-CBCT maneuvers increased navigation yield to 75% (P=0.02) and diagnostic yield to 70% (P=0.04). One patient developed a pneumothorax. Conclusions: CBCT-guided bronchoscopy is associated with an acceptable radiation dose. CBCT may potentially increase both navigation and diagnostic yield of thin/ultrathin bronchoscopy for peripheral lung nodules. The above findings as well as the incidental but relevant finding of intra-procedural atelectasis need to be confirmed in larger prospective studies. Trial registration: This study is registered in ClinicalTrials.gov as number NCT02978170.

Despite the many advances in peripheral bronchoscopy, its diagnostic yield remains suboptimal. With the use of cone-beam CT imaging we have found atelectasis mimicking lung tumors or obscuring them when using radial-probe endobronchial ultrasound (RP-EBUS), but its incidence remains unknown.What are the incidence, anatomic location, and risk factors for developing atelectasis during bronchoscopy under general anesthesia?We performed a prospective observational study in which patients undergoing peripheral bronchoscopy under general anesthesia were subject to an atelectasis survey carried out by RP-EBUS under fluoroscopic guidance. The following dependent segments were evaluated: right bronchus 2 (RB2), RB6, RB9, and RB10; and left bronchus 2 (LB2), LB6, LB9, and LB10. Images were categorized either as aerated lung ("snowstorm" pattern) or as having a nonaerated/atelectatic pattern. Categorization was performed by three independent readers.Fifty-seven patients were enrolled. The overall intraclass correlation agreement among readers was 0.82 (95% CI, 0.71-0.89). Median time from anesthesia induction to atelectasis survey was 33 min (range, 3-94 min). Fifty-one patients (89%; 95% CI, 78%-96%) had atelectasis in at least one of the eight evaluated segments, 45 patients (79%) had atelectasis in at least three, 41 patients (72%) had atelectasis in at least four, 33 patients (58%) had atelectasis in at least five, and 18 patients (32%) had atelectasis in at least six segments. Right and left B6, B9, and B10 segments showed atelectasis in50% of patients. BMI and time to atelectasis survey were associated with increased odds of having more atelectatic segments (BMI: OR, 1.13 per unit change; 95% CI, 1.034-1.235; P = .007; time to survey: OR, 1.064 per minute; 95% CI, 1.025-1.105; P = .001).The incidence of atelectasis developing during bronchoscopy under general anesthesia in dependent lung zones is high, and the number of atelectatic segments is greater with higher BMI and with longer time under anesthesia.ClinicalTrials.gov; No.: NCT03523689; URL: www.clinicaltrials.gov.

Background Population aging and lung cancer screening strategies may lead to an increase in detection of early-stage lung cancer in medical inoperable patients. Recent advances in peripheral bronchoscopy have made it a suitable platform for ablation of small peripheral tumors. Methods We investigated the tissue-ablative effect of a diode laser bronchoscopically applied by a laser delivery fiber (LDF) with wide aperture on porcine lung parenchyma. Laser was tested ex vivo and in vivo to identify the most effective power settings and LDF. Chest computed tomography (CT) were obtained immediately after ablation and after 3 days of observation. At day 3, necropsy was performed. Results On the basis of our ex vivo and in vivo experiments, we selected the round-tip LDF to be activated at 25 W for 20 seconds. Ten ablations were performed in 5 pigs. One ablation resulted in a pneumothorax requiring aspiration. All animals remained stable for 72 hours. CT findings at days 1 and 3 showed an area of cavitation surrounded by consolidation and ground glass. Median size of CT findings (long axis) was 26 mm (range, 24 to 38) at day 1, and 34 mm (range, 30 to 44) at day 3. Necropsy showed an area of central char measuring from 0.8×0.7×0.9 cm to 2.4×3.5×1.2 cm, surrounded by a gray-brown to dark red area. On histology, variable degrees of necrosis were evident around the charred areas. Conclusion Bronchoscopic laser interstitial thermal therapy can achieve relatively large areas of ablation of normal lung parenchyma with a low rate of periprocedural complications.

BackgroundWhile therapeutic bronchoscopy has been used to treat malignant central (CAO) airway obstruction for >25 years, there are no studies quantifying the impact of therapeutic bronchoscopy on long-term quality-adjusted survival.MethodsWe conducted a prospective observational study of consecutive patients undergoing therapeutic bronchoscopy for CAO. Patients had follow-up at 1 week and monthly thereafter until death. Outcomes included technical success (ie, relief of anatomic obstruction), dyspnoea, health-related quality of life (HRQOL) and quality-adjusted survival.ResultsTherapeutic bronchoscopy was performed on 102 patients with malignant CAO. Partial or complete technical success was achieved in 90% of patients. At 7 days postbronchoscopy, dyspnoea improved (mean ∆Borg-day-7=−1.8, 95% CI −2.2 to −1.3, pConclusionsTherapeutic bronchoscopy improves HRQOL as compared with baseline, resulting in approximately a 5.8% improvement in HRQOL per day of life. The risk-benefit profile in these carefully selected patients was very favourable.Trial registration numberResults; NCT03326570.

Objective Expiratory functions that clear aspiration from the airway are compromised in patients with neurogenic dysphagia for whom cough and expiratory force may be impaired by the primary disease process. The relationship between expiratory function, cough, and aspiration is less clear in head and neck cancer (HNC) survivors for whom the disease process does not directly impact the lower respiratory system. Our objective was to compare mechanisms of airway clearance (expiratory force and cough) with aspiration status in postradiated HNC survivors. Study design Cross-sectional study. Methods One hundred and three disease-free HNC survivors ≥ 3-months postradiotherapy referred for modified barium swallow studies were prospectively enrolled regardless of dysphagia status. Maximum expiratory pressures (MEPs) and peak cough flow (PCF) measures were taken at enrollment and examined as a function of aspiration status using generalized linear regression methods. Results Thirty-four (33%) patients aspirated. Maximum expiratory pressure and PCF demonstrated a moderate positive correlation (Pearson's r = 0.35). Adjusting for sex and age, MEPs were on average 19.2% lower (21.1 cm H2 O, 95% confidence interval [CI] 5.3, 36.8) among aspirators. Peak cough flow was also 14.9% lower (59.6 L/minute, 95% CI 15.8, 103.3) among aspirators after adjusting for age and sex. Conclusion Expiratory functions were depressed in postradiated HNC aspirators relative to nonaspirators, suggesting that airway protection impairments may extend beyond disrupted laryngopharyngeal mechanisms in the local treatment field. Exercises to strengthen subglottic expiratory force-generating capacity may offer an adjunctive therapeutic target to improve airway protection in chronic aspirators after head and neck radiotherapy. Level of evidence 2b. Laryngoscope, 128:1615-1621, 2018.

Background and objective Standard nodal staging of lung cancer consists of positron emission tomography/computed tomography (PET/CT), followed by endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) if PET/CT shows mediastinal lymphadenopathy. Sensitivity of EBUS-TBNA in patients with N0/N1 disease by PET/CT is unclear and largely based on retrospective studies. We assessed the sensitivity of EBUS-TBNA in this setting. Methods We enrolled patients with proven or suspected lung cancer staged as N0/N1 by PET/CT and without metastatic disease (M0), who underwent staging EBUS-TBNA. Primary outcome was sensitivity of EBUS-TBNA compared with a composite reference standard of surgical stage or EBUS-TBNA stage if EBUS demonstrated N2/N3 disease. Results Seventy-five patients were included in the analysis. Mean tumour size was 3.52 cm (±1.63). Fifteen of 75 patients (20%) had N2 disease. EBUS-TBNA identified six while nine were only identified at surgery. Sensitivity of EBUS-TBNA for N2 disease was 40% (95% CI: 16.3-67.7%). Conclusion A significant proportion of patients with N0/N1 disease by PET/CT had N2 disease (20%) and EBUS-TBNA identified a substantial fraction of these patients, thus improving diagnostic accuracy compared with PET/CT alone. Sensitivity of EBUS-TBNA however appears lower compared with historical data from patients with larger volume mediastinal disease. Therefore, strategies to improve EBUS-TBNA accuracy in this population should be further explored.

Pulmonary manifestations of lymphoma and leukemia may involve multiple structures within the thoracic cavity. Malignant lymphoma typically originates in lymph nodes, but concomitant or primary presentations with parenchymal, pleural, or tracheobronchial disease may occur. Once infection is excluded, leukemic infiltrates may be related to malignancy, hemorrhage, or secondary pulmonary alveolar proteinosis. Confirmation with cytology or flow cytometry is recommended to diagnose malignant pleural effusions in hematologic malignancies. In chronic leukemia with progressive pulmonary findings, exclusion of a synchronous malignancy or Richter syndrome should be performed. Venous thromboembolism may present in patients with leukemia and lymphoma despite the presence of thrombocytopenia.

Interventional pulmonology (IP) is a rapidly evolving subspecialty of pulmonary medicine. In the last 10 years, formal IP fellowships have increased substantially in number from five to now > 30. The vast majority of IP fellowship trainees are selected through the National Resident Matching Program, and validated in-service and certification examinations for IP exist. Practice standards and training guidelines for IP fellowship programs have been published; however, considerable variability in the environment, curriculum, and experience offered by the various fellowship programs remains, and there is currently no formal accreditation process in place to standardize IP fellowship training. Recognizing the need for more uniform training across the various fellowship programs, a multisociety accreditation committee was formed with the intent to establish common accreditation standards for all IP fellowship programs in the United States. This article provides a summary of those standards and can serve as an accreditation template for training programs and their offices of graduate medical education as they move through the accreditation process.

© 2019 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited. Background: The behavior of pleural fluid cytokine (PFCs) levels and their association with pleurodesis after indwelling pleural catheter (IPC) placement is unknown. Objective: A prospective exploratory study was conducted to obtain preliminary data on PFC levels after IPC placement. Methods: The PFC panel consisted of 4 cytokines [interleukin -8 (IL-8), vascular endothelial growth factor, total (but not activated) transforming growth factor betas, and basic fibroblast growth factor], measured across 5 time points (T0: insertion; T1: 24 to 48 h; T2: 72 to 96 h; T3: 1 wk; and T4: 2 wk). Profile plots were used to identify patterns of change of PFC levels. Correlation matrices for each PFC over time were computed, and area under the curve (AUC) categories were used to compare the cumulative incidence of IPC removal. Auto pleurodesis was defined as elective catheter removal because of decreased drainage within 90 days of insertion. Results: A total of 22 patients provided complete data. Except for IL-8, the majority of PFCs demonstrated strong positive correlations across measurement time points. Patients with high AUCs for IL-8, basic fibroblast growth factor, and vascular endothelial growth factor had a higher cumulative incidence of IPC removal by 90 days than did patients with low AUCs. Conclusion: This is the first study to evaluate longitudinal changes of pleural cytokine levels with respect to the likelihood of IPC removal and provide early evidence that the cytokine profile may be associated with the outcome of pleurodesis induced by IPCs. However, this is an exploratory study and further studies are needed to assess if these findings can be validated in further studies.

Importance Stereotactic ablative radiotherapy (SABR) is first-line treatment for patients with early-stage non–small cell lung cancer (NSCLC) who cannot undergo surgery. However, up to 1 in 6 such patients will develop isolated local recurrence (iLR) or isolated regional recurrence (iRR). Little is known about outcomes when disease recurs after SABR, or about optimal management strategies for such recurrences. Objective To characterize long-term outcomes for patients with iLR or iRR after SABR for early-stage NSCLC with the aim of informing treatment decision making for these patients with potentially curable disease. Design, Setting, and Participants In this cohort study, a retrospective review was conducted of 912 patients prospectively enrolled in an institutional database at a tertiary cancer center from January 1, 2004, through December 31, 2014. Main Outcomes and Measures Overall survival, progression-free survival, recurrence patterns, demographics, salvage techniques, patterns of salvage failure, and toxic effects. Results Of the 912 patients in the study (456 women and 456 men; median age, 72 years [range, 46-91 years]), 756 (82.9%) had T1 tumors at initial diagnosis; 502 tumors (55.0%) were adenocarcinomas and 309 tumors (33.9%) were squamous cell carcinomas. Of 912 patients with early-stage I to II NSCLC who received definitive SABR (50 Gy in 4 fractions or 70 Gy in 10 fractions), 102 developed isolated recurrence (49 with iLR and 53 with iRR), and 658 had no recurrence. Median times to recurrence after SABR were 14.5 months (range, 1.5-60.8 months) for iLR and 9.0 months (range, 1.9-70.7 months) for iRR; 39 of 49 patients (79.6%) with iLR and 48 of 53 patients (90.6%) with iRR underwent salvage with reirradiation, surgery, thermal ablation, or chemotherapy. Median follow-up times for patients with iLR or iRR were 57.2 months (interquartile range, 37.7-87.6 months) from initial SABR and 38.5 months (interquartile range, 19.9-69.3 months) from recurrence. Rates of overall survival at 5 years from initial SABR were no different between patients with iLR and salvage treatment (57.9%) and patients with no recurrence (54.9%; hazard ratio, 0.89; 95% CI, 0.56-1.43; P = .65) but were lower for patients with iRR and salvage treatment (31.1%; hazard ratio, 1.43; 95% CI, 1.00-2.34; P = .049). Patients receiving salvage treatment had longer overall survival than patients who did not (median, 37 vs 7 months after recurrence; hazard ratio, 0.40; 95% CI, 0.09-0.66; P = .006). Twenty-four of 87 patients (27.6%) who received salvage treatment for iLR or iRR subsequently developed distant metastases. No patient experienced grade 5 toxic effects after salvage treatment. Conclusions and Relevance Life expectancy after salvage treatment for iLR was similar to that for patients without recurrence, but survival after salvage treatment for iRR was similar to that of patients with stage III NSCLC. Patients who received salvage treatment had significantly improved survival. Because salvage treatment for iLR or iRR was based on a consistent multidisciplinary approach, this may help in clinical decision making., This cohort study examines long-term outcomes for patients with isolated local recurrence or isolated regional recurrence after stereotactic ablative radiotherapy for early-stage non–small cell lung cancer with the aim of informing treatment decision making., Key Points Question What are the outcomes for potentially curable local or regional recurrences after stereotactic ablative radiotherapy for early-stage non–small cell lung cancer? Findings In this cohort study of 912 patients who received stereotactic ablative radiotherapy for early-stage I to II non–small cell lung cancer, salvage treatment was significantly associated with improved survival. Survival for patients with local recurrence who received salvage treatment was no different than that for patients with no recurrence, and survival for patients with regionally recurrent disease was similar to that for patients with stage III disease. Meaning This study provides data on outcomes for patients with recurrence after stereotactic ablative radiotherapy, which may help in clinical decision making.

The standard approach to staging of lung cancer in patients with pleural effusion (clinical M1a) is thoracentesis followed by pleural biopsies if the cytologic analysis is negative. If pleural biopsy findings are negative, endobronchial ultrasound-guided transbronchial needle aspiration is used to complete the staging process and, in some cases, obtain diagnosis. In this case series we report 7 patients in which a combined procedure was performed for staging of known or suspected lung cancer. We found that the combined approach was both feasible and safe in this case series. Keywords: Pleuroscopy, Endobronchial ultrasound

Lung adenocarcinoma (LUAD) is the most frequently diagnosed histological subtype of lung cancer and accounts for most smoking-related cancer deaths, warranting strategies for early intervention. Earlier work revealed genome-wide aberrations in LUADs and the adjacent premalignant field, known as “field carcinogenesis”, that are pertinent to LUAD pathogenesis. Yet, we still poorly understand the cellular and molecular architecture of LUAD and its nearby “field”. To fill this void, we performed, using the 10X Genomics system and NovaSeq 6000 platform, single-cell RNA sequencing (scRNA-seq) analysis of 4 early-stage resected LUADs as well as 11 matched normal lung tissues with differing spatial proximity from the tumors. We first analyzed 15,739 cells from a LUAD and matched tumor-adjacent and -distant normal tissues from patient 1. The resulting fraction of EPCAM+ cells from this analysis was approximately 4%. For deeper single-cell resolution of LUAD, we thus performed scRNA-seq of separately sorted/enriched epithelial cells (EPCAM+; n = 50,883) and non-epithelial cells (EPCAM-; n= 91,093) from patients 2, 3 and 4, each with an early-stage LUAD and three matched spatially-distributed normal-appearing tissues. Overall, we achieved on average approximately 150,000 reads and 1,956 genes detected per cell. Divergent populations of malignant and non-malignant cells and multiple epithelial and immune subsets clustered in an overall spatially modulated pattern according to proximity to the tumor. Hierarchical clustering revealed multiple distinct populations of airway lineage cells, including alveolar type 1 (AT1), alveolar type 2 (AT2), AT1/AT2 bipotential cells, club, goblet, basal and ciliated cells, with cells from the resected LUAD present in some but not all clusters. By analysis of epithelial-enriched fractions, we were also able to identify and interrogate rare cell subpopulations including CFTR-expressing ionocytes. By inference of copy number variation along with analysis of key oncogene expression patterns, we also identified epithelial cells that represent potential tumor cells-of-origin. Spatial reprogramming of field carcinogenesis encompassed immune cell populations including tumor-exclusive FOXP3+ regulatory T cells with marked over-expression of the major immune checkpoints CTLA4 and TIGIT. In contrast, for at least some of the cases, tumors were nearly devoid of natural killer cells, and abundance of CD8+ T cells dampened with increasing proximity to the tumor. Our single-cell surveys offer insights into novel cues in LUAD pathogenesis. Efforts are underway to interrogate the single-cell epithelial and immune landscape of additional LUADs and matched nearby normal-appearing lung, including those from non-smokers, to better understand the evolution of the disease and, thus, identify a low-hanging fruit of targets for early management of this fatal malignancy. Citation Format: Ansam Sinjab, Guangchun Han, Warapen Treekitkarnmongkol, Patrick Brennan, Kieko Hara, Kyle Chang, Elena Bogatenkova, Beatriz Sanchez-Espiridion, Carmen Behrens, Jianjun Zhang, Boris Sepesi, Tina Cascone, Don L. Gibbons, Jichao Chen, George Eapen, Edwin J. Ostrin, Junya Fujimoto, Avrum E. Spira, Paul A. Scheet, Ignacio I. Wistuba, Linghua Wang, Humam Kadara. A single-cell transcriptomic atlas of lung adenocarcinoma and adjacent normal-appearing tissue [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1518.

BackgroundThoracentesis using suction is perceived to have increased risk of complications, including pneumothorax and re-expansion pulmonary oedema (REPO). Current guidelines recommend limiting drainage to 1.5 L to avoid REPO. Our purpose was to examine the incidence of complications with symptom-limited drainage of pleural fluid using suction and identify risk factors for REPO.MethodsA retrospective cohort study of all adult patients who underwent symptom-limited thoracentesis using suction at our institution between January 1, 2004 and August 31, 2018 was performed, and a total of 10 344 thoracenteses were included.ResultsPleural fluid ≥1.5 L was removed in 19% of the procedures. Thoracentesis was stopped due to chest discomfort (39%), complete drainage of fluid (37%) and persistent cough (13%). Pneumothorax based on chest radiography was detected in 3.98%, but only 0.28% required intervention. The incidence of REPO was 0.08%. The incidence of REPO increased with Eastern Cooperative Oncology Group performance status (ECOG PS) ≥3 compounded with ≥1.5 L (0.04–0.54%; 95% CI 0.13–2.06 L). Thoracentesis in those with ipsilateral mediastinal shift did not increase complications, but less fluid was removed (pConclusionsSymptom-limited thoracentesis using suction is safe even with large volumes. Pneumothorax requiring intervention and REPO are both rare. There were no increased procedural complications in those with ipsilateral mediastinal shift. REPO increased with poor ECOG PS and drainage ≥1.5 L. Symptom-limited drainage using suction without pleural manometry is safe.

Flexible bronchoscopy has changed the course of pulmonary medicine. As technology advances, the role of the flexible bronchoscope for both diagnostic and therapeutic indications is continually expanding. This article reviews the historical development of the flexible bronchoscopy, fundamental uses of the flexible bronchoscope as a tool to examine the central airways and obtain diagnostic tissue, and the indications, complications, and contraindications to flexible bronchoscopy.

BACKGROUND There are significant variations in how therapeutic bronchoscopy for malignant airway obstruction is performed. Relatively few studies have compared how these approaches affect the incidence of complications. METHODS We used the American College of Chest Physicians (CHEST) Quality Improvement Registry, Evaluation, and Education (AQuIRE) program registry to conduct a multicenter study of patients undergoing therapeutic bronchoscopy for malignant central airway obstruction. The primary outcome was the incidence of complications. Secondary outcomes were incidence of bleeding, hypoxemia, respiratory failure, adverse events, escalation in level of care, and 30-day mortality. RESULTS Fifteen centers performed 1,115 procedures on 947 patients. There were significant differences among centers in the type of anesthesia (moderate vs deep or general anesthesia, P .001), use of rigid bronchoscopy ( P .001), type of ventilation (jet vs volume cycled, P .001), and frequency of stent use (P P = .002). Risk factors for complications were urgent and emergent procedures, American Society of Anesthesiologists (ASA) score > 3, redo therapeutic bronchoscopy, and moderate sedation. The 30-day mortality was 14.8%; mortality varied among centers (range, 7.7%-20.2%, P = .02). Risk factors for 30-day mortality included Zubrod score > 1, ASA score > 3, intrinsic or mixed obstruction, and stent placement. CONCLUSIONS Use of moderate sedation and stents varies significantly among centers. These factors are associated with increased complications and 30-day mortality, respectively.

BACKGROUND There is significant variation between physicians in terms of how they perform therapeutic bronchoscopy, but there are few data on whether these differences impact effectiveness. METHODS This was a multicenter registry study of patients undergoing therapeutic bronchoscopy for malignant central airway obstruction. The primary outcome was technical success, defined as reopening the airway lumen to > 50% of normal. Secondary outcomes were dyspnea as measured by the Borg score and health-related quality of life (HRQOL) as measured by the SF-6D. RESULTS Fifteen centers performed 1,115 procedures on 947 patients. Technical success was achieved in 93% of procedures. Center success rates ranged from 90% to 98% ( P = .02). Endobronchial obstruction and stent placement were associated with success, whereas American Society of Anesthesiology (ASA) score > 3, renal failure, primary lung cancer, left mainstem disease, and tracheoesophageal fistula were associated with failure. Clinically significant improvements in dyspnea occurred in 90 of 187 patients measured (48%). Greater baseline dyspnea was associated with greater improvements in dyspnea, whereas smoking, having multiple cancers, and lobar obstruction were associated with smaller improvements. Clinically significant improvements in HRQOL occurred in 76 of 183 patients measured (42%). Greater baseline dyspnea was associated with greater improvements in HRQOL, and lobar obstruction was associated with smaller improvements. CONCLUSIONS Technical success rates were high overall, with the highest success rates associated with stent placement and endobronchial obstruction. Therapeutic bronchoscopy should not be withheld from patients based solely on an assessment of risk, since patients with the most dyspnea and lowest functional status benefitted the most.

A patient diagnosed with pulmonary embolism had persistent symptoms despite adequate therapy. Tissue sampling with endobronchial ultrasound-guided needle aspiration revealed endovascular metastasis from a prior early-stage colorectal cancer. We describe the challenges in the diagnosis and workup of suspected tumor emboli.

Data regarding the sensitivity of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) for staging of lung cancer in patients with radiographic N0 disease is scant and inconsistent. With increasing use of nonoperative ablative therapies, studies focusing on the performance characteristics of EBUS-TBNA in this population are important.To evaluate the sensitivity and negative predictive value (NPV) of EBUS-TBNA in patients with non-small cell lung cancer and radiographic N0 disease both by computed tomography (CT) and positron emission tomography (PET)-CT.This was a retrospective review of EBUS-TBNA performed for lung cancer staging at two major academic centers from 2009 to 2014. Patients with radiographic N0 disease (lymph nodes [LN]≤1 cm in the short axis and maximum standardized uptake value≤2.5 by PET-CT) were included. Primary outcome was sensitivity and NPV of EBUS-TBNA.Two hundred twenty patients with radiographic N0 disease underwent EBUS-TBNA, and 734 LN were sampled (median 3, range 1-6). Median LN diameter was 0.72 cm. One hundred patients (45.5%) underwent surgery, and 120 patients (54.5%) had nonsurgical therapy. N status was up-staged in 49 patients (22.3%): 18 by EBUS-TBNA (N1=11, N2=6, N3=1), 27 by surgery (N1 intralobar=16, N1 extralobar=3, N2=8 [5 LN in stations 4 and 7, and 3 LN in stations 5-6), and 4 by imaging follow-up (N1=2, N2=2). Overall false-negative rate of EBUS was 14.1% (sensitivity, 36.7%; specificity, 100%; and NPV, 84.7%). False-negative rate was 27 and 3.3% in surgical and nonsurgical populations, respectively. Excluding patients with occult disease "outside" the reach of EBUS, the overall false-negative rate of EBUS-TBNA was 5.5% (sensitivity, 60%; specificity, 100%; and NPV, 93.4%).This is the largest report of EBUS-TBNA in patients with N0 disease by "integrated" PET-CT. The majority of false-negative EBUS results were in LN stations outside its reach. In our study, both sensitivity and NPV of EBUS-TBNA were lower than early reports despite more extensive LN sampling. Given the high false-negative rate of imaging modalities, EBUS-TBNA may still play an important role in patients with radiographic N0 disease, particularly when nonsurgical ablative therapies are planned. Prospective studies are needed to corroborate our findings in the nonsurgical population.

Ultrasound is an imaging modality that utilizes the mechanical properties of high-frequency sound waves when passing through tissues of different densities to produce images of the interrogated tissue. Ultrasound has long been used to image thoracic structures, and the use of an ultrasound endoscope allowing visualization of structures surrounding the esophagus was first described in 1980 [1]. In the early 1990s, endobronchial ultrasound (EBUS) was introduced, dramatically changing the practice of bronchoscopy [2, 3]. Before the advent of EBUS, the bronchoscopist’s view was limited to those structures visualized within the airways or with fluoroscopy. The bronchoscopist can now visualize the structures surrounding the airway wall using EBUS. This chapter will review the clinical applications of EBUS. A more detailed discussion of the technical aspects of EBUS will be undertaken elsewhere in this text.

Endobronchial ultrasound (EBUS) has transformed mediastinal staging in lung cancer. A systematic approach, beginning with lymph nodes contralateral to the primary tumor (N3), is considered superior to selective sampling of radiographically abnormal nodes. However, the extent to which this recommendation is followed in practice remains unknown.To assess the frequency with which pulmonologists, pulmonary fellows, and interventional pulmonologists endoscopically stage lung cancer appropriately.Bronchoscopists currently performing EBUS were surveyed about their practice patterns, procedural volume, and self-confidence in EBUS skills; they then performed a proctored simulated staging EBUS. The primary outcome was the proportion of participants who appropriately initiated ultrasonographic evaluation with the N3 nodal stations in a simulated patient undergoing EBUS for mediastinal staging.Sixty physicians (22 interventional pulmonologists, 18 general pulmonologists, and 20 pulmonary fellows) participated in the study. The rates of appropriate staging by study group were 95.5% (21 of 22) for interventional pulmonologists, 44.4% (8 of 18) for general pulmonologists, and 30.0% (6 of 20) for pulmonary fellows (P 0.001). Increased procedural volume correlated with appropriate staging practices (P 0.001). Within each group, we assessed the concordance between self-confidence in EBUS and simulation performance. Among interventional pulmonologists, the concordance was 95.4%, followed by 61.1% for general pulmonologists and 40.0% for pulmonary fellows.General pulmonologists and pulmonary fellows were less likely than interventional pulmonologists to perform appropriate EBUS staging. In addition, the lack of concordance between self-confidence and appropriate staging performance among noninterventionists signals a need for improved dissemination of guidelines for EBUS-guided mediastinal staging.

Rationale: Endobronchial ultrasound (EBUS) has transformed mediastinal staging in lung cancer. A systematic approach, beginning with lymph nodes contralateral to the primary tumor (N3), is considered superior to selective sampling of radiographically abnormal nodes. However, the extent to which this recommendation is followed in practice remains unknown.Objectives: To assess the frequency with which pulmonologists, pulmonary fellows, and interventional pulmonologists endoscopically stage lung cancer appropriately.Methods: Bronchoscopists currently performing EBUS were surveyed about their practice patterns, procedural volume, and self-confidence in EBUS skills; they then performed a proctored simulated staging EBUS. The primary outcome was the proportion of participants who appropriately initiated ultrasonographic evaluation with the N3 nodal stations in a simulated patient undergoing EBUS for mediastinal staging.Results: Sixty physicians (22 interventional pulmonologists, 18 general pulmonologists, and 2...

Malignant pleural effusions (MPEs) are a frequent cause of dyspnea in patients with cancer. Although indwelling pleural catheters (IPCs) have been used since 1997, there are no studies of quality-adjusted survival following IPC placement.With a standardized algorithm, this prospective observational cohort study of patients with MPE treated with IPCs assessed global health-related quality of life using the SF-6D to calculate utilities. Quality-adjusted life days (QALDs) were calculated by integrating utilities over time.A total of 266 patients were enrolled. Median quality-adjusted survival was 95.1 QALDs. Dyspnea improved significantly following IPC placement (Plt; .001), but utility increased only modestly. Patients who had chemotherapy or radiation after IPC placement (Plt; .001) and those who were more short of breath at baseline (P = .005) had greater improvements in utility. In a competing risk model, the 1-year cumulative incidence of events was death with IPC in place, 35.7%; IPC removal due to decreased drainage, 51.9%; and IPC removal due to complications, 7.3%. Recurrent MPE requiring repeat intervention occurred in 14% of patients whose IPC was removed. Recurrence was more common when IPC removal was due to complications (P = .04) or malfunction (Plt; .001) rather than to decreased drainage.IPC placement has significant beneficial effects in selected patient populations. The determinants of quality-adjusted survival in patients with MPE are complex. Although dyspnea is one of them, receiving treatment after IPC placement is also important. Future research should use patient-centered outcomes in addition to time-to-event analysis.ClinicalTrials.gov; No.: NCT01117740; URL: www.clinicaltrials.gov.

Estimating the probability of finding N2 or N3 (prN2/3) malignant nodal disease on endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) in patients with non-small cell lung cancer (NSCLC) can facilitate the selection of subsequent management strategies.To develop a clinical prediction model for estimating the prN2/3.We used the AQuIRE (American College of Chest Physicians Quality Improvement Registry, Evaluation, and Education) registry to identify patients with NSCLC with clinical radiographic stage T1-3, N0-3, M0 disease that had EBUS-TBNA for staging. The dependent variable was the presence of N2 or N3 disease (vs. N0 or N1) as assessed by EBUS-TBNA. Univariate followed by multivariable logistic regression analysis was used to develop a parsimonious clinical prediction model to estimate prN2/3. External validation was performed using data from three other hospitals.The model derivation cohort (n = 633) had a 25% prevalence of malignant N2 or N3 disease. Younger age, central location, adenocarcinoma histology, and higher positron emission tomography-computed tomography N stage were associated with a higher prN2/3. Area under the receiver operating characteristic curve was 0.85 (95% confidence interval, 0.82-0.89), model fit was acceptable (Hosmer-Lemeshow, P = 0.62; Brier score, 0.125). We externally validated the model in 722 patients. Area under the receiver operating characteristic curve was 0.88 (95% confidence interval, 0.85-0.90). Calibration using the general calibration model method resulted in acceptable goodness of fit (Hosmer-Lemeshow test, P = 0.54; Brier score, 0.132).Our prediction rule can be used to estimate prN2/3 in patients with NSCLC. The model has the potential to facilitate clinical decision making in the staging of NSCLC.

11600 Background: High flow oxygen therapy is effective for hypoxemic respiratory failure. However, its effect on dyspnea in non-hypoxemic patients is unknown. In this 2x2 factorial, double-blind randomized clinical trial, we assessed the effect of flow rate (high vs. low) and gas (oxygen vs. air) on exertional dyspnea in cancer patients. Methods: Non-hypoxemic patients with cancer completed two structured cycle ergometer exercise tests with Low Flow Air [LFAir] at 2 L/min. They were then randomized to receive High Flow Oxygen [HFOx] with up to 60 L/min, High Flow Air [HFAir], Low Flow Oxygen [LFOx] or LFAir during a constant work rate exercise test at 80% maximum. Dyspnea intensity was assessed with the modified 0-10 Borg scale. The primary outcome was difference in the slope of dyspnea intensity vs. time during the third test. Secondary outcomes included difference in exercise time, vital signs, and adverse events. We estimated that 10 patients per arm will provide 86% power to detect a 1-standard deviation main effect and 86% power to detect a 2-SD interaction effect with an alpha of 5%. A linear mixed effects model was used to assess the impact of flow rate and gas on study outcomes. Results: 45 patients were randomized and 44 completed the study (10, 11, 12, 11 patients on HFOx, HFAir, LFOx, LFAir, respectively). The mean age was 63 (range 47-77); 18 (41%) were female; 34 (44%) had lung cancer; and 20 (46%) had metastatic disease. In mixed effects model, the association between the change in dyspnea intensity over time with flow rate differed significantly between oxygen and air (P = 0.04). Specifically, HFOx (slope difference -0.20, P < 0.001) and LFOx (-0.14, P = 0.01) were significantly better than LFAir, but not HFAir (+0.09, P = 0.09). Exercise time also significantly increased with HFOx (difference +2.5 min, P = 0.009) compared to LFAir, but not HFAir (+0.63 min, P = 0.48) or LFOx (+0.39 min, P = 0.65). HFOx was well tolerated without significant adverse effects. Conclusions: The combination of high flow rate and oxygen improved dyspnea and exercise duration during constant work exercise test in non-hypoxemic cancer patients. Larger trials are needed to confirm the benefits of HFOx during exercises. Clinical trial information: NCT02357134.

Background and objective Microdebrider bronchoscopy is a relatively new modality for the management of central airway obstruction (CAO) of both benign and malignant origin. Our objective was to describe our experience with this technique, with special attention to its safety and effectiveness. Methods We retrospectively reviewed cases of therapeutic bronchoscopies using microdebrider for CAO from two institutions (M.D. Anderson Cancer Center and Michael E. Debakey VA Medical Center, Houston) from August 2008 through February 2012. Results We identified 51 cases. Malignant CAO was detected in 36 cases (71%): non-small-cell lung cancer (n = 22), melanoma (n = 3), small-cell-lung cancer (n = 2), thyroid cancer (n = 2), esophageal carcinoma (n = 2), breast cancer (n = 2), and others (n = 3). Benign diseases included: papillomas (n = 8), granulation tissue (n = 3), and others (n = 4). Obstruction was purely endoluminal in 32 cases (63%). Pre-treatment obstruction was severe in 25 cases (49%), moderate in 20 cases (39%) and mild in 6 (12%). Lesions were located in the trachea (n = 23), main stem bronchi (n = 25), and bronchus intermedius (n = 8), with some patients having more than one lesion. After tumor debulking with microdebrider, the residual airway obstruction was insignificant (n = 27 cases; 53%), mild (n = 23 cases; 45%), and moderate (n = 1; 2%). No major complications were encountered, only 2 patients had mild adverse events: one case of pneumomediastinum, and one self-expandable stent damage requiring its removal. Two patients (4%) died within 30 days of causes unrelated to the procedure or the CAO. Conclusions Microdebrider bronchoscopy is a potentially safe and effective way to manage central airway obstruction of both malignant and benign origin.

Background Few studies of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) have been large enough to identify risk factors for complications. The primary objective of this study was to quantify the incidence of and risk factors for complications in patients undergoing EBUS-TBNA. Methods Data on prospectively enrolled patients undergoing EBUS-TBNA in the American College of Chest Physicians Quality Improvement Registry, Evaluation, and Education (AQuIRE) database were extracted and analyzed for the incidence, consequences, and predictors of complications. Results We enrolled 1,317 patients at six hospitals. Complications occurred in 19 patients (1.44%; 95% CI, 0.87%–2.24%). Transbronchial lung biopsy (TBBx) was the only risk factor for complications, which occurred in 3.21% of patients who underwent the procedure and in 1.15% of those who did not (OR, 2.85; 95% CI, 1.07-7.59; P = .04). Pneumothorax occurred in seven patients (0.53%; 95% CI, 0.21%–1.09%). Escalations in level of care occurred in 14 patients (1.06%; 95% CI, 0.58%–1.78%); its risk factors were age > 70 years (OR, 4.06; 95% CI, 1.36-12.12; P = .012), inpatient status (OR, 4.93; 95% CI, 1.30-18.74; P = .019), and undergoing deep sedation or general anesthesia (OR, 4.68; 95% CI, 1.02-21.61; P = .048). TBBx was performed in only 12.6% of patients when rapid onsite cytologic evaluation (ROSE) was used and in 19.1% when it was not used ( P = .006). Interhospital variation in TBBx use when ROSE was used was significant ( P Conclusions TBBx was the only risk factor for complications during EBUS-TBNA procedures. ROSE significantly reduced the use of TBBx.

Interventional pulmonology (IP) is a rapidly evolving subspecialty of pulmonary medicine. In the last 10 years, formal IP fellowships have increased substantially in number from five to now30. The vast majority of IP fellowship trainees are selected through the National Resident Matching Program, and validated in-service and certification examinations for IP exist. Practice standards and training guidelines for IP fellowship programs have been published; however, considerable variability in the environment, curriculum, and experience offered by the various fellowship programs remains, and there is currently no formal accreditation process in place to standardize IP fellowship training. Recognizing the need for more uniform training across the various fellowship programs, a multisociety accreditation committee was formed with the intent to establish common accreditation standards for all IP fellowship programs in the United States. This article provides a summary of those standards and can serve as an accreditation template for training programs and their offices of graduate medical education as they move through the accreditation process.

Background Patients with non-small cell lung cancer (NSCLC) being evaluated for stereotactic ablative body radiotherapy (SABR) are typically staged noninvasively with positron emission tomography/computed tomography (PET/CT). Incorporating endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) into the staging workup of these patients has not been evaluated. Our primary objective was to compare the performance of PET/CT with EBUS-TBNA for intrathoracic nodal assessment among SABR-eligible patients. Methods This was a retrospective study consisting of two parts. First, we assessed the concordance for nodal metastasis of PET/CT and EBUS-TBNA. Second, we evaluated clinical outcomes among patients who underwent SABR with and without a prior EBUS-TBNA. Results We identified 246 eligible patients. Compared with PET/CT, EBUS-TBNA led to a stage shift in 48 of 246 patients (19%). Of 174 N0 patients by PET/CT, 6 (3.4%) had nodal metastasis on EBUS-TBNA. Among 72 clinical N1 patients, 36 (50%) were downstaged to N0 after EBUS-TBNA, therefore becoming eligible for SABR. Concordance between PET/CT and EBUS-TBNA for nodal metastasis was 83% (κ = 0.53). Clinical outcomes of patients who underwent SABR with or without a prior EBUS-TBNA did not differ significantly. Conclusions Concordance of PET/CT and EBUS-TBNA for nodal disease was only moderate. Incorporating EBUS-TBNA into the staging workup was beneficial in identifying occult nodal metastasis that would otherwise be left untreated with SABR and in expanding the pool of potentially SABR-eligible patients.

Pleural effusions are rarely observed in patients with acute myelogenous leukemia (AML), acute lymphocytic leukemia (ALL) and myelodysplastic syndrome (MDS)/myeloproliferative neoplasm (MPN). Therefore the underlying etiology of pleural effusions and the efficacy and safety of pleural procedures in this population has not been well studied. In a retrospective review of cases from 1997 to 2007, we identified 111 patients with acute leukemia or MDS/MPN who underwent pleural procedures. Clinical characteristics were reviewed, and survival outcomes were estimated by Kaplan-Meier methods. A total of 270 pleural procedures were performed in 111 patients (69 AML, 27 ALL, 15 MDS/MPN). The main indications for pleural procedures were possible infection (49%) and respiratory symptoms (48%), and concomitant clinical symptoms included fever (34%), dyspnea (74%), chest pain (24%) and cough (37%). Most patients had active disease (61%). The most frequent etiology of pleural effusions was infection (47%), followed by malignancy (36%). Severe thrombocytopenia (platelet count < 20 × 10(3)/µL) was present in 43% of the procedures, yet the procedural complication rate was only 1.9%. Multivariate analysis revealed that older age, AML, MDS/MPN and active disease status were associated with a shorter median overall survival. Infection and malignant involvement are the most common causes of pleural effusion in patients with acute leukemia or MDS. After optimizing platelet count and coagulopathy, thoracentesis may be performed safely and with high diagnostic yield in this population. Survival in these patients is determined by the response to treatment of the hematologic malignancy.

Lung cancer screening with LDCT is a complex and controversial topic, with inherent risks and benefits. Results from the large, prospective, randomized NLST show that lung cancer screening with LDCT can decrease lung cancer–specific mortality by 20% and even decrease all-cause mortality by 7%.8 The NLST results indicate that to prevent one death from lung cancer, 320 high-risk individuals must be screened with LDCT. However, the NLST findings have not been replicated yet in a separate cohort. Further analysis of the NLST is underway, including comparative effectiveness modeling. The cost-effectiveness and true benefit-to-risk ratio for lung cancer screening still must be determined. At some point, an acceptable level of risk will have to be deemed appropriate for the benefits of screening. The NCCN Lung Cancer Screening Panel recommends helical LDCT screening for select patients at high risk for lung cancer based on the NLST results, nonrandomized studies, and observational data. These guidelines discuss in detail the criteria for determining which patients are at high risk, and the algorithm provides recommendations for evaluating and following-up nodules detected on LDCT screening (e.g., solid and part-solid nodules). Smokers should always be encouraged to quit smoking tobacco (http://www.smokefree.gov/). Programs using behavioral counseling combined with medications that promote smoking cessation (approved by the FDA) can be very useful (see Treating Tobacco Use and Dependence: Quick Reference Guide for Clinicians; http://www.surgeongeneral.gov/tobacco/tobaqrg.htm). When considering lung cancer screening, it is important to have a full understanding of all risks and benefits related to screening with LDCT. As policies for implementing lung screening programs are designed, a focus on multidisciplinary programs (incorporating primary care doctors, pulmonologists, radiologists, thoracic surgeons, medical oncologists, and pathologists) will be helpful to optimize decision-making and minimize interventions for patients with benign lung disease.

Background New transbronchial needle aspiration (TBNA) technologies have been developed, but their clinical effectiveness and determinants of diagnostic yield have not been quantified. Prospective data are needed to determine risk-adjusted diagnostic yield. Methods We prospectively enrolled patients undergoing TBNA of mediastinal lymph nodes in the American College of Chest Physicians Quality Improvement Registry, Evaluation, and Education (AQuIRE) multicenter database and recorded clinical, procedural, and provider information. All clinical decisions, including type of TBNA used (conventional vs endobronchial ultrasound-guided), were made by the attending bronchoscopist. The primary outcome was obtaining a specific diagnosis. Results We enrolled 891 patients at six hospitals. Most procedures (95%) were performed with ultrasound guidance. A specific diagnosis was made in 447 cases. Unadjusted diagnostic yields were 37% to 54% for different hospitals, with significant between-hospital heterogeneity ( P = .0001). Diagnostic yield was associated with annual hospital TBNA volume (OR, 1.003; 95% CI, 1.000-1.006; P = .037), smoking (OR, 1.55; 95% CI, 1.02-2.34; P = .042), biopsy of more than two sites (OR, 0.57; 95% CI, 0.38-0.85; P = .015), lymph node size (reference > 1-2 cm, ≤ 1 cm: OR, 0.51; 95% CI, 0.34-0.77; P = .003; > 2-3 cm: OR, 2.49; 95% CI, 1.61-3.85; P 3 cm: OR, 3.61; 95% CI, 2.17-6.00; P P = .018). Biopsy was performed on more and smaller nodes at high-volume hospitals ( P Conclusions To our knowledge, this is the first bronchoscopy study of risk-adjusted diagnostic yields on a hospital-level basis. High-volume hospitals were associated with high diagnostic yields. This study also demonstrates the value of procedural registries as a quality improvement tool. A larger number and variety of participating hospitals is needed to verify these results and to further investigate other determinants of diagnostic yield.

Radical surgery for malignant pleural mesothelioma does not improve survival in patients with nodal metastases. Imaging is poor at predicting nodal involvement and mediastinoscopy, though frequently used, is of low sensitivity. As endobronchial ultrasound (EBUS) and esophageal endoscopic ultrasound (EUS) are accurate for nodal staging of lung cancer, we hypothesized that they would be at least as sensitive as cervical video-mediastinoscopy for nodal staging of mesothelioma.Eighty-five patients with mesothelioma who were potential candidates for radical surgery underwent preoperative staging with mediastinoscopy (n = 50) or EBUS (n = 38). Eleven patients also underwent EUS.Diagnostic yield (specimens containing lymphocytes or tumor cells) was 100% for mediastinoscopy and 84% for EBUS (p0.001). Mediastinoscopy identified 7 of 50 (14%) patients with nodal metastases. Thirty-eight (76%) mediastinoscopy-negative patients underwent surgery with nodal sampling and there were 18 false negatives. Endobronchial ultrasound identified 13 of 38 (34%) patients with nodal metastases. Twenty-two (58%) EBUS-negative patients underwent surgery with nodal sampling and there were 10 false negatives. Sensitivity and negative predictive value for mediastinoscopy were 28% and 49%, and 59% and 57% for EBUS. Eleven patients had EUS preoperatively, which revealed infradiaphragmatic nodal metastases in 5 patients.Although this study is retrospective, EBUS had higher sensitivity than either mediastinoscopy or imaging studies for detection of nodal metastases. Nevertheless, the ability to accurately identify nodal involvement preoperatively in patients with mesothelioma remains suboptimal. Esophageal ultrasound may complement EBUS particularly in cases where infradiaphragmatic nodal metastases are suspected.