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Background: A well-recognized therapy to improve the symptoms of patients with malignant pleural effusion (MPE), indwelling pleural catheters (IPCs) can also achieve spontaneous pleurodesis. Chemical pleurodesis is associated with a significant pro-coagulation and fibrinolytic environment. Hence, anticoagulation could theoretically interfere with this process. Objective: The aim of this study was to evaluate if anticoagulation can interfere with successful spontaneous pleurodesis in patients treated with IPC. Methods: This was a cohort study of all patients with MPE treated with IPC. The primary objective was to determine if anticoagulant use after IPC placement decreased the rate of spontaneous pleurodesis. The secondary objective was to identify other factors associated with spontaneous pleurodesis. We used a Fine-Gray subdistribution hazard model and a direct acyclic graph to identify variables associated with time to spontaneous pleurodesis. Results: Of the included 410 patients, 210 patients (51.2%) achieved pleurodesis and had their IPC removed. We found no association between anticoagulation and likelihood of pleurodesis. Multivariate analyses revealed that prior chemotherapy, ECOG score of 2–4 were associated with unsuccessful pleurodesis, while chemotherapy or radiotherapy after IPC placement remained associated with increased likelihood of spontaneous pleurodesis. Conclusions: We failed to demonstrate an association between anticoagulation and pleurodesis. We found that better performance status and chemotherapy or radiotherapy after IPC placement can increase the rate of pleurodesis and catheter removal.

Pleuroscopy with pleural biopsy has a high sensitivity for malignant pleural effusion (MPE). Because MPEs tend to recur, concurrent diagnosis and treatment of MPE during pleuroscopy is desired. However, proceeding directly to treatment at the time of pleuroscopy requires confidence in the on-site diagnosis. The study's primary objective was to create a predictive model to estimate the probability of MPE during pleuroscopy.A prospective observational multicentre cohort study of consecutive patients undergoing pleuroscopy was conducted. We used a logistic regression model to evaluate the probability of MPE with relation to visual assessment, rapid on-site evaluation (ROSE) of touch preparation and presence of pleural nodules/masses on computed tomography (CT). To assess the model's prediction accuracy, a bootstrapped training/testing approach was utilized to estimate the cross-validated area under the receiver operating characteristic curve.Of the 201 patients included in the study, 103 had MPE. Logistic regression showed that higher level of malignancy on visual assessment is associated with higher odds of MPE (OR = 34.68, 95% CI = 9.17-131.14, p 0.001). The logistic regression also showed that higher level of malignancy on ROSE of touch preparation is associated with higher odds of MPE (OR = 11.63, 95% CI = 3.85-35.16, p 0.001). Presence of pleural nodules/masses on CT is associated with higher odds of MPE (OR = 6.61, 95% CI = 1.97-22.1, p = 0.002). A multivariable logistic regression model of final pathologic status with relation to visual assessment, ROSE of touch preparation and presence of pleural nodules/masses on CT had a cross-validated AUC of 0.94 (95% CI = 0.91-0.97).A prediction model using visual assessment, ROSE of touch preparation and CT scan findings demonstrated excellent predictive accuracy for MPE. Further validation studies are needed to confirm our findings.

Background The optimal diagnostic and staging strategy for patients with suspected lung cancer is not known. Research Question What diagnostic and staging strategies are most cost-effective for lung cancer? Study Design and Methods A decision model was developed by using a hypothetical patient with a high probability of lung cancer. Sixteen unique permutations of bronchoscopy with fluoroscopy, radial endobronchial ultrasound, electromagnetic navigation, convex endobronchial ultrasound with or without rapid-onsite evaluation (ROSE), CT-guided biopsy (CTBx), and surgery were evaluated. Outcomes included cost, complications, mortality, time to complete the evaluation, rate of undetected N2-3 disease at surgery, incremental cost-complication ratio, and willingness-to-pay thresholds. Sensitivity analyses were performed on primary outcomes. Results For a peripheral lung lesion and radiographic N0 disease, the best bronchoscopy strategy costs $1,694 more than the best CTBx strategy but resulted in fewer complications (risk difference, 14%). The additional cost of bronchoscopy to avoid one complication from a CTBx strategy was $12,037. The cost and cumulative complications of bronchoscopy strategies increased compared with CTBx strategies for small lesions. The cost and cumulative complications of bronchoscopy strategies decreased compared with CTBx strategies when a bronchus sign was present, but bronchoscopy remained more costly overall. For a central lesion and/or radiographic N1-3 disease, convex endobronchial ultrasound with ROSE followed by lung biopsy with incremental cost-effectiveness ratio, if required, was more cost-effective than any CTBx strategy across all outcomes. Strategies with ROSE were always more cost-effective than those without, irrespective of scenario. Trade-offs also exist between different bronchoscopy strategies, and optimal choices depend on the value placed on individual outcomes and willingness-to-pay. Interpretation The most cost-effective strategies depend on nodal stage, lesion location, type of peripheral bronchoscopic biopsy, and the use of ROSE. For most clinical scenarios, many strategies can be eliminated, and trade-offs between the remaining competitive strategies can be quantified.

Background Evidence-based guidelines recommend management strategies for malignant pleural effusions (MPEs) based on life expectancy. Existent risk-prediction rules do not provide precise individualized survival estimates. Research Question Can a newly developed continuous risk-prediction survival model for patients with MPE and known metastatic disease provide precise survival estimates? Study Design and Methods Single-center retrospective cohort study of patients with proven malignancy, pleural effusion, and known metastatic disease undergoing thoracentesis from 2014 through 2017. The outcome was time from thoracentesis to death. Risk factors were identified using Cox proportional hazards models. Effect-measure modification (EMM) was tested using the Mantel-Cox test and was addressed by using disease-specific models (DSMs) or interaction terms. Three DSMs and a combined model using interactions were generated. Discrimination was evaluated using Harrell’s C-statistic. Calibration was assessed by observed-minus-predicted probability graphs at specific time points. Models were validated using patients treated from 2010 through 2013. Using LENT (pleural fluid lactate dehydrogenase, Eastern Cooperative Oncology Group performance score, neutrophil-to-lymphocyte ratio and tumor type) variables, we generated both discrete (LENT-D) and continuous (LENT-C) models, assessing discrete vs continuous predictors’ performances. Results The development and validation cohort included 562 and 727 patients, respectively. The Mantel-Cox test demonstrated interactions between cancer type and neutrophil to lymphocyte ratio (P Interpretation EMM is present between cancer type and other predictors; thus, DSMs outperformed the models that failed to account for this. Discrete risk-prediction models lacked enough precision to be useful for individual-level predictions.

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.

AimsIn advanced-stage non-small-cell lung cancer (NSCLC), incomplete genotyping for guideline-recommended genomic biomarkers poses a significant challenge to making informed and timely clinical decisions. We report our institution’s experience in assessing the adequacy of small specimens for comprehensive genomic profiling for guideline-recommended lung cancer biomarker testing.MethodsWe performed a retrospective evaluation of all image-guided procedures for NSCLC performed in our institution between October 2016 and July 2018, including core needle biopsy (CNB) and fine-needle aspiration (FNA) in patients who had undergone genomic profiling for lung cancer. Lung cancer biomarker adequacy, defined as successful testing of guideline-recommended biomarkers including, epidermal growth factor receptor (EGFR); serine/threonine protein kinase B-Raf (BRAF); anaplastic lymphoma kinase (ALK); proto-oncogene tyrosine protein kinase ROS (ROS1); Rearranged during Transfection (RET); Tyrosine protein kinase Met (MET); and programmed cell death ligand 1 (PD-L1), was evaluated.ResultsA total of 865 cases were evaluated in this study, 785 of which included testing of all lung cancer biomarkers. Lung tissue was adequate for biomarker testing in 84% of cases; this rate increased to 87% when biomarker testing was combined with concurrently acquired FNA or CNB specimens. Biomarker testing success correlated strongly with DNA concentration (pConclusionThe growing numbers of therapeutic biomarkers in NSCLC requires judicious triage of limited-volume tissue from small specimens. Our study showed that thoracic small tissue specimens can be used successfully to provide prognostic and predictive information for the current guideline-recommended biomarkers for NSCLC in most cases.

Rationale: Patients with malignant/paramalignant pleural effusions (MPE/PMPEs) may have tunneled pleural catheter (TPC) management withheld due to infection concerns from immunosuppression associated with antineoplastic therapy. Objective: To determine the rate of infections related to TPC use and to determine the relationship to antineoplastic therapy, immune system competency and overall survival (OS)? Methods: We performed an international, multi-institutional study of MPE/PMPE patients undergoing TPC management from 2008-2016. Patients were stratified by whether or not they underwent antineoplastic therapy and/or were immunocompromised or not. Cumulative incidence functions and multivariable competing risk regression analyses were performed to identify independent predictors of TPC-related infection. Kaplan-Meier method and multivariable Cox proportional-hazards modeling were performed to examine for independent effects on OS. Results: A total of 1,408 TPCs were placed in 1,318 patients. Patients had a high frequency of overlap between antineoplastic therapy and an immunocompromised state (75-83%). No difference in the overall (6-7%), deep pleural (3-5%) or superficial (3-4%) TPC-related infection rates between subsets of patients stratified by antineoplastic therapy or immune status was observed. The median time to infection was 41 (interquartile range: 19-87) days following TPC insertion. Multivariable competing risk analyses demonstrated longer TPC duration was associated with a higher risk of TPC-related infection [subdistribution hazard ratio (95% CI): 1.03 (1.00-1.06), p=0.028]. Cox proportional-hazards analysis showed antineoplastic therapy was associated with better OS [hazard ratio (95% CI): 0.84 (0.73-0.97), p=0.015]. Conclusion: The risk of TPC-related infection does not appear to be increased by antineoplastic therapy use or an immunocompromised state. The overall rates of infection are low and comparable to immunocompetent patients with no relevant antineoplastic therapy. These results support TPC palliation for MPE/PMPE regardless of plans for antineoplastic therapy.

Background Systematic endobronchial ultrasound (EBUS)-guided lung cancer staging starts with hilar N3 nodes, proceeding sequentially to mediastinal N3, N2, and N1 nodes, with sampling of all enlarged nodes (size, ≥ 5 mm) by EBUS. However, procedure time is limited by patient comfort when moderate sedation is used. It is unclear if EBUS staging should start with hilar N3 nodes or whether starting with mediastinal N3 nodes suffices. Knowing the probability of hilar N3 nodes with PET-CT scan negative findings harboring occult metastasis can inform this decision. Research Question What proportion of patients with hilar N3 nodes showing negative PET-CT scan findings have malignancy by EBUS? Study Design and Methods This retrospective observational, single-center cohort study included consecutive patients with clinical-radiographic T1-3, N0-3, M0 non-small cell lung cancer undergoing systematic EBUS staging with biopsy of hilar N3 nodes with negative PET-CT scan findings. The primary outcome was the proportion of patients with malignant hilar N3 nodes showing negative PET-CT scan findings. Based on expert opinion, a threshold probability of malignancy of less than 5% was considered sufficient to skip hilar N3 nodes. We used the binomial exact test to compare the observed proportion vs threshold probability of 5%. Results Of 1,737 consecutive patients undergoing EBUS staging, 1,567 showed negative PET-CT scan findings of the hilar N3 nodes. These nodes were enlarged by EBUS and were sampled in 739 patients. Malignancy was found in the hilar N3 nodes of 5 of 739 patients (0.68%; 95% CI, 0.22%-1.57%). The proportion was significantly less than the threshold probability (P Interpretation When using moderate sedation, because time is limited, it is reasonable to start with the mediastinal N3 nodes if the hilar and mediastinal N3 nodes show negative PET scan results. Patients with positive PET scan findings of the mediastinal N3 nodes probably should undergo hilar N3 node sampling.

Background Thyroid malignancies are among the most common endocrine cancers worldwide. Owing to the angiogenic nature of these malignancies, tyrosine kinase inhibitors (TKIs) are an attractive potential treatment. However, TKIs have been associated with an increased risk of tumor cavitation, in turn linked to poor outcomes, in patients with malignancies in the lungs, where thyroid cancer commonly metastasizes. Method We performe d a retrospective cohort study of patients with thyroid cancer and evidence of metastatic disease to the lung that were treated with multi-targeted antiangiogenic TKIs. The primary objective of this study was to determine the incidence of pulmonary cavitation. The secondary objective was to evaluate the effect of pulmonary cavitation on survival. Results Of the 83 patients with pulmonary nodules, 10 developed cavitation during treatment. Of these 83 patients, two patients had to stop the treatment due to pneumothorax. Additionally, cavitation did not demonstrate any significant effect on survival. Conclusion In patients with thyroid cancer and evidence of metastatic disease to the chest, the use of multi-targeted TKIs led to cavitations that were not uncommon but clinical consequences were marginal. Treatment was stopped only in two patients that developed pneumothorax, however the small sample is a strong limitation of our study.

Background 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. Research Question What are the incidence, anatomic location, and risk factors for developing atelectasis during bronchoscopy under general anesthesia? Study Design and Methods 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. Results 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 in > 50% 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). Interpretation 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. Clinical Trial Registration ClinicalTrials.gov ; No.: NCT03523689; URL: www.clinicaltrials.gov .

Background The management of recurrent pleural effusions remains a challenging issue for clinicians. Advances in management have led to increased use of indwelling tunneled pleural catheters (IPC) because of their effectiveness and ease of outpatient placement. However, with the increase in IPC placement there have also been increasing reports of complications, including infections. Currently there is minimal guidance in IPC-related management issues after placement. Research Question Our objective was to formulate clinical consensus statements related to perioperative and long-term IPC catheter management based on a modified Delphi process from experts in pleural disease management. Study Design and Methods Expert panel members used a modified Delphi process to reach consensus on common perioperative and long-term management options related to IPC use. Members were identified from multiple countries, specialties, and practice settings. A series of meetings and anonymous online surveys were completed. Responses were used to formulate consensus statements among panel experts, using a modified Delphi process. Consensus was defined a priori as greater than 80% agreement among panel constituents. Results A total of 25 physicians participated in this project. The following topics were addressed during the process: definition of an IPC infection, management of IPC-related infectious complications, interventions to prevent IPC infections, IPC-related obstruction/malfunction management, assessment of IPC removal, and instructions regarding IPC management by patients and caregivers. Strong consensus was obtained on 36 statements. No consensus was obtained on 29 statements. Interpretation The management of recurrent pleural disease with IPC remains complex and challenging. This statement offers statements for care in numerous areas related to IPC management based on expert consensus and identifies areas that lack consensus. Further studies related to long-term management of IPC are warranted.

Background Thoracentesis can be accomplished by active aspiration or drainage with gravity. This trial investigated whether gravity drainage could protect against negative pressure-related complications such as chest discomfort, re-expansion pulmonary edema, or pneumothorax compared with active aspiration. Methods This prospective, multicenter, single-blind, randomized controlled trial allocated patients with large free-flowing effusions estimated ≥ 500 mL 1:1 to undergo active aspiration or gravity drainage. Patients rated chest discomfort on 100-mm visual analog scales prior to, during, and following drainage. Thoracentesis was halted at complete evacuation or for persistent chest discomfort, intractable cough, or other complication. The primary outcome was overall procedural chest discomfort scored 5 min following the procedure. Secondary outcomes included measures of discomfort and breathlessness through 48 h postprocedure. Results A total of 142 patients were randomized to undergo treatment, with 140 in the final analysis. Groups did not differ for the primary outcome (mean visual analog scale score difference, 5.3 mm; 95% CI, –2.4 to 13.0; P = .17). Secondary outcomes of discomfort and dyspnea did not differ between groups. Comparable volumes were drained in both groups, but the procedure duration was significantly longer in the gravity arm (mean difference, 7.4 min; 95% CI, 10.2 to 4.6; P Conclusions Thoracentesis via active aspiration and gravity drainage are both safe and result in comparable levels of procedural comfort and dyspnea improvement. Active aspiration requires less total procedural time. Trial Registry ClinicalTrials.gov; No.: NCT03591952; URL: www.clinicaltrials.gov.

Clinical decisions for NSCLC patients are often based on TNM stage, which does not account for different histological subtype. Whether histological subtype affects survival still remains unclear. The main objective of this study was to determine the extent to which the survival outcomes of patients with early-stage NSCLC differ by histological subtype.Retrospective cohort study of SEER data base. Patients with stage IA and IB NSCLC that underwent surgery with lymph node dissection were included. The primary outcome was the time to death. Cox proportional hazards models were used to identify risk factors associated with overall survival (OS). The secondary outcome was the time to death from lung cancer. A Cox model and a Fine-Gray subdistribution hazards model in which death from causes other than lung cancer was considered a competing risk event were used to identify risk factors for death from lung cancer.Analysis of the SEER database identified 28,584 NSCLC patients, of whom 19,750 (69 %) had adenocarcinoma and 8834 (31 %) had squamous cell carcinoma. In the multivariate for OS, older age (p 0.001), male gender (p 0.001), pneumonectomy (p 0.001), larger tumor size (p 0.001), squamous cell carcinoma (p 0.001) not being Hispanic or Asian were associated with increased risk of death. In the competing risk model, older age (p 0.001), male gender (p 0.001), pneumonectomy (p 0.001), larger tumor size (p 0.001), and squamous cell carcinoma (p 0.001) were was associated with an increased risk of death from lung cancer.This study suggests that among patients with stage I NSCLC, those with squamous histology have a higher risk of mortality than those with adenocarcinoma histology taking into account competing risks.

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...

Background The use of pleuroscopy has expanded over the last decade due to its higher diagnostic yield and low complications rate. Whether the infectious complications of pleuroscopy performed in negative pressure rooms is similar to that of pleuroscopy performed in positive pressure rooms remain unclear. To assess the safety of pleuroscopy performed in negative pressure rooms, we sought to determine the rate of infectious complications in patients who underwent pleuroscopy in negative pressure bronchoscopy rooms at our institution. Methods This was a retrospective cohort study of all patients who underwent pleuroscopy in our institution's negative pressure bronchoscopy rooms between January 2005 and January 2018. The primary outcome was the incidence of infectious complications at 14 and 30 days after the procedure. Results We identified 318 patients. Of the 318 patients, 47 (15%) had hematological malignancies, 118 (37%) had lung cancer, 121 (38%) had solid non-lung cancers, and 32 (10%) had no cancer diagnosis before the procedure. At the end of pleuroscopy, 255 patients (80%) had an indwelling pleural catheter placed, 63 patients (20%) had only a chest tube placed, and 31 patients (9%) had both an indwelling pleural catheter and chest tube placed. No patients developed empyema within 14 days. Three patients (0.9%) developed empyema within 30 days after the procedure and was presumed to be due to pleural catheter infection in all cases. Conclusion Our findings show that pleuroscopy performed in negative pressure rooms has a low incidence of infectious complications, provided that proper sterile precautions are maintained.

BACKGROUND AND OBJECTIVE Analysis of programmed death ligand-1 (PD-L1) in tumour samples is necessary to identify candidates for anti-PD-L1/PD-L1 therapy. Because PD-L1 is evaluated by immunohistochemistry (IHC), an adequate amount of tumour tissue is a prerequisite for PD-L1 testing. To examine whether pleural fluid might be an alternative to biopsy/resection specimens for IHC evaluation of PD-L1 in patients with non-small cell lung carcinoma (NSCLC), we compared PD-L1 by IHC between histological specimens and matched pleural fluid. METHODS A retrospective cohort study of patients with NSCLC who underwent core biopsy of a lung mass/surgical resection with PD-L1 IHC and had a pleural fluid cell block (CB) available for PD-L1 staining was conducted. PD-L1 was categorized as negative (PD-L1 in

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.

Lung cancer is the current leading cause of cancer-related deaths worldwide, and malignant pleural effusion, an indicator of the advanced stage of this disease, portends a poor prognosis. Thus, making an accurate diagnosis of malignant pleural effusion is of paramount importance. During the past decade, the prognosis of patients with advanced non-small cell lung cancer has improved substantially, especially in those treated with targeted therapy and immunotherapy. The use of pleural fluid cytology should not only provide diagnoses but also aid in the selection of targeted therapies, especially when obtaining a histologic specimen is too difficult. In this evidence-based review, we address the importance of pleural fluid cytology in non-small cell lung cancer patients, from making the diagnosis to making treatment-related decisions when only pleural fluid is available.

A 63-year-old male with non-small-cell lung cancer (NSCLC) developed a tracheomediastinal fistula after endobronchial ultrasound transbronchial needle aspiration while on treatment with bevacizumab. This vascular endothelial growth factor-specific angiogenesis inhibitor is a first-line treatment for unresectable or metastatic NSCLC and has been reported to cause fatal non-gastrointestinal fistulas. Respiratory tract fistulas are a known rare complication after bevacizumab therapy characterized by a high mortality rate.

The optimal diagnostic and staging strategy for patients with suspected lung cancer is not known.What diagnostic and staging strategies are most cost-effective for lung cancer?A decision model was developed by using a hypothetical patient with a high probability of lung cancer. Sixteen unique permutations of bronchoscopy with fluoroscopy, radial endobronchial ultrasound, electromagnetic navigation, convex endobronchial ultrasound with or without rapid-onsite evaluation (ROSE), CT-guided biopsy (CTBx), and surgery were evaluated. Outcomes included cost, complications, mortality, time to complete the evaluation, rate of undetected N2-3 disease at surgery, incremental cost-complication ratio, and willingness-to-pay thresholds. Sensitivity analyses were performed on primary outcomes.For a peripheral lung lesion and radiographic N0 disease, the best bronchoscopy strategy costs $1,694 more than the best CTBx strategy but resulted in fewer complications (risk difference, 14%). The additional cost of bronchoscopy to avoid one complication from a CTBx strategy was $12,037. The cost and cumulative complications of bronchoscopy strategies increased compared with CTBx strategies for small lesions. The cost and cumulative complications of bronchoscopy strategies decreased compared with CTBx strategies when a bronchus sign was present, but bronchoscopy remained more costly overall. For a central lesion and/or radiographic N1-3 disease, convex endobronchial ultrasound with ROSE followed by lung biopsy with incremental cost-effectiveness ratio, if required, was more cost-effective than any CTBx strategy across all outcomes. Strategies with ROSE were always more cost-effective than those without, irrespective of scenario. Trade-offs also exist between different bronchoscopy strategies, and optimal choices depend on the value placed on individual outcomes and willingness-to-pay.The most cost-effective strategies depend on nodal stage, lesion location, type of peripheral bronchoscopic biopsy, and the use of ROSE. For most clinical scenarios, many strategies can be eliminated, and trade-offs between the remaining competitive strategies can be quantified.

Although our understanding of the pathogenesis of empyema has grown tremendously over the past few decades, questions still remain on how to optimally manage this condition. It has been almost a decade since the publication of the MIST2 trial, but there is still an extensive debate on the appropriate use of intrapleural fibrinolytic and deoxyribonuclease therapy in patients with empyema. Given the scarcity of overall guidance on this subject, we convened an international group of 22 experts from 20 institutions across five countries with experience and expertise in managing adult patients with empyema. We did a literature and internet search for reports addressing 11 clinically relevant questions pertaining to the use of intrapleural fibrinolytic and deoxyribonuclease therapy in adult patients with bacterial empyema. This Position Paper, consisting of seven graded and four ungraded recommendations, was formulated by a systematic and rigorous process involving the evaluation of published evidence, augmented with provider experience when necessary. Panel members participated in the development of the final recommendations using the modified Delphi technique. Our Position Paper aims to address the existing gap in knowledge and to provide consensus-based recommendations to offer guidance in clinical decision making when considering the use of intrapleural therapy in adult patients with bacterial empyema.

Background Pulmonary carcinoids, which are well-differentiated lung neuroendocrine carcinomas, account for only 1–2 % of primary lung malignancies. Although fluorodeoxyglucose positron-emission tomography/computed tomography performs poorly in the identification of mediastinal lymph node metastases, particularly for pulmonary carcinoids, endobronchial ultrasound-guided (EBUS) transbronchial needle aspiration (TBNA) may be a useful means of preoperative nodal assessment in patients with these conditions. However, the diagnostic performance of EBUS TBNA is unknown. This study was designed to determine the sensitivity of EBUS for mediastinal staging in patients with typical carcinoid. Study design and methods A retrospective review of all patients with carcinoids who underwent EBUS TBNA and/or surgical resection with lymphadenectomy at The University of Texas MD Anderson Cancer Center was performed. The sensitivity of EBUS –TBNA in diagnosis of mediastinal lymph node metastases was determined. Results Of the 212 patients with pulmonary carcinoids we identified, 137 had surgery with no preoperative EBUS TBNA, 68 had EBUS TBNA followed by surgery, and 7 had EBUS TBNA only. The sensitivity rate for EBUS TBNA in diagnosis of mediastinal lymph node metastases was 77.78 % overall (95 % CI, 57.7−91.3%) and it was 87.5 % (95 % CI, 67.6−97.3%) when we considered only patients with EBUS TBNA-accessible lymph nodes. Discussion The sensitivity of EBUS TBNA for diagnosis of mediastinal lymph node metastases of pulmonary carcinoids was slightly lower than that reported previously for non-small cell lung cancer. Preoperative EBUS TBNA identified nodal metastases not previously identified by imaging.

BACKGROUND. Pulmonary hypertension (PH) has been described in myelofibrosis (MF), but it is rare and typically found in advanced disease. Although the etiology of PH in MF is unclear, early predictors may be detected by echocardiogram. The goals of our study were to evaluate the prevalence of PH as determined by echocardiography in a cohort of MF patients and to identify clinical risk factors for PH. METHODS. We performed a retrospective review of MF patients from October 2015 to May 2017 at MD Anderson Cancer Center in the ambulatory clinic, and those with echocardiogram were included. Clinical, echocardiographic and laboratory data were reviewed. Patients with and without PH were compared using a chi-square or Fisher exact test, and logistic regression was performed with an outcome variable of PH. RESULTS. There were 143 patients with MF who underwent echocardiogram, and 20(14%) had echocardiographic findings consistent with PH. Older age, male gender, hypertension, hyperlipidemia, coronary artery disease, dyspnea, hematocrit, brain natriuretic peptide(BNP) and N-terminal-pro hormone BNP(NT-proBNP) were significantly different between those without PH and those with PH(p

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.

Thymomas are slow-growing neoplasia arising from the epithelial cells of the thymus that usually present with respiratory symptoms, superior vena cava syndrome, or parathymic syndromes. Approximately 30% of thymomas develop myasthenia gravis. An additional 5% of patients with thymomas have other systemic syndromes, including rheumatoid arthritis, thyroiditis, red cell aplasia, systemic lupus erythematosus, and Cushing syndrome. Rarely, patients can present with diarrhea due to thymoma-associated autoimmune gastrointestinal pathologies that include Good syndrome (acquired hypogammaglobulinemia), thymoma- associated multiorgan autoimmunity, and autoimmune enteropathy. We present an uncommon and interesting case of an invasive metastatic thymoma with right upper lobe endobronchial lesion and autoimmune enteropathy in a 27-year-old female. The novelty of this case lay in the findings of extensive metastatic thymoma with right upper lobe endobronchial disease and autoimmune diarrhea.

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.

Transdifferentiation from non-small cell lung cancer (NSCLC) to small cell lung cancer (SCLC) has been reported mostly in adenocarcinomas and has been described as a cause of acquired tyrosine kinase inhibitor (TKI) resistance. However, transdifferentiation has also been described in patients with different histologic characteristics and patients not exposed to TKIs and with no epidermal growth factor receptor (EGFR) mutation (the target of TKIs). To this date transdifferentiation remains poorly understood. We conducted a retrospective case series of patients who had biopsy-proven SCLC within 2 years after a diagnosis of NSCLC or in the same location as the known primary NSCLC. We found that 0.2% of lung cancer patients at our institution experienced transdifferentiation. Among these, 30 had adenocarcinoma and 16 had squamous cell carcinoma. In 27 of the 30 patients with adenocarcinoma (90%), SCLC was found in the same location as the known primary. In 14 of the 30 patients (47%), SCLC occurred within 2 years after the NSCLC diagnosis. In 12 of the 16 patients with squamous cell carcinoma (75%), SCLC was found in the same location as the known primary. In 8 of these 16 patients (50%), SCLC occurred within 2 years after the NSCLC diagnosis. Few patients with adenocarcinoma and none with squamous cell carcinoma were treated with TKIs or had an EGFR mutation. In conclusion the findings in the current study suggest that the discovery of SCLC histology after treatment of NSCLC may be more common than thought suggesting that further study is warranted to evaluate the phenomenon of transdifferentiation.

BACKGROUND AND OBJECTIVE: The main purpose of treatment in patients with malignant pleural effusion (MPE) is symptom palliation. Currently, patients undergo repeat thoracenteses prior to receiving a definitive procedure as clinicians are not aware of the risk factors associated with fluid recurrence. The primary objective of this study was to identify risk factors associated with recurrent symptomatic MPE. METHODS: Retrospective multicentre cohort study of patients who underwent first thoracentesis was performed. The primary outcome was time to fluid recurrence requiring intervention in patients with evidence of metastatic disease. We used a cause-specific hazard model to identify risk factors associated with fluid recurrence. We also developed a predictive model, utilizing Fine–Gray subdistribution hazard model, and externally validated the model. RESULTS: A total of 988 patients with diagnosed metastatic disease were included. Cumulative incidence of recurrence was high with 30% of patients recurring by day 15. On multivariate analysis, size of the effusion on chest X-ray (up to the top of the cardiac silhouette (hazard ratio (HR): 1.84, 95% CI: 1.21–2.80, P = 0.004) and above the cardiac silhouette (HR: 2.22, 95% CI: 1.43–3.46, P = 0.0004)), larger amount of pleural fluid drained (HR: 1.06, 95% CI: 1.04–1.07, P < 0.0001) and higher pleural fluid LDH (HR: 1.008, 95% CI: 1.004–1.011, P < 0.0001) were associated with increased hazard of recurrence. Negative cytology (HR: 0.52, 95% CI: 0.43–0.64, P < 0.0001) was associated with decreased hazard of recurrence. The model had low prediction accuracy. CONCLUSION: Pleural effusion size, amount of pleural fluid drained, LDH and pleural fluid cytology were found to be risk factors for recurrence.

Background: The optimal approach to sedation for pleuroscopy remains undefined. Propofol is the favored sedative-hypnotic for many proceduralists but has a narrow therapeutic window and the risk for oversedation is high. Propofol-based sedation administered by anesthesiologists and the routine use of end-tidal capnography and bispectral index (BIS) monitoring may attenuate risks of complications. Objectives: The purpose of our study was to evaluate the safety and efficacy of monitored anesthesia care for pleuroscopy. Methods: We conducted a retrospective cohort study of patients who underwent pleuroscopy. The primary outcome of interest was the incidence of anesthesia complications in patients undergoing pleuroscopy. Hypoxia was defined as oxygen saturation of less than 90% for 2 min and hypotension was defined as the need for vasopressors. Results: Of 199 enrolled patients, there were no significant complications attributed directly to anesthesia. Minor complications included hypoxia in 9 patients (4.5%), hypotension in 76 patients (38.2%), and insertion of a nasopharyngeal tube airway in 2 patients (1.0%). There was no significant difference in anesthesia-related complications between those with BIS monitoring and those without. Lower mean oxygen saturations (p = 0.028) and hypoxia (p = 0.021) were found in patients receiving the combination of propofol plus narcotics plus sedatives compared to those receiving propofol only, propofol plus narcotics or propofol plus sedatives. Conclusion: Our study demonstrates that pleuroscopy using propofol with end-tidal capnography monitoring, with or without BIS monitoring, is safe and effective. The combination of propofol with narcotics and sedatives is associated with more hypoxia and lower mean oxygen saturation compared with propofol alone, propofol plus narcotics or propofol plus sedatives.

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.