Complications following symptom-limited thoracentesis using suction.

BACKGROUND: Thoracentesis 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. METHODS: A 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. RESULTS: Pleural 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 (p<0.01). CONCLUSIONS: Symptom-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.

Incidence of Bleeding Complications With Flexible Bronchoscopy in Cancer Patients With Thrombocytopenia.

BACKGROUND: Bronchoscopy is a safe procedure, but current guidelines recommend transfusion for platelets <20 K/µL. Studies of bronchoscopy in thrombocytopenia are limited. OBJECTIVES: Our objective was to evaluate the incidence of bleeding with flexible bronchoscopy in those with thrombocytopenia especially those <20 K/µL. METHOD: We performed a retrospective review of all flexible bronchoscopies between June 1, 2008 and December 31, 2010. Biopsies and therapeutic procedures were excluded. The χ, Fisher exact, and Rank-sum test were conducted to evaluate associations of clinically significant bleeding. RESULTS: There were 1711 patients who underwent 2053 flexible bronchoscopies. Cancer diagnosis included hematologic (61.3%) and solid organ malignancy (34.9%). Half of the bronchoscopies had moderate to severe thrombocytopenia (<100 K/µL) with the following ranges: 14.7% with 50 to <100 K/µL, 20.6% with 20 to <50 K/µL, 10.6% with 10 to <20 K/µL, 4.1% with <10 K/µL. Platelet transfusion was given in 90.6% of those with platelets <10 K/µL and 55.5% of those with platelets 10 to <20 K/µL. The nasal route for bronchoscopy was used in 92.4%. Bleeding complication rate however was 1.1% (0.2% major) and not affected by platelets. CONCLUSION: Bronchoscopy with lavage can be safely performed without platelet transfusion in those with platelets of ≥10 K/µL. In the absence of nasal bleeding, trauma, or deformity, the nasal route can be used for bronchoscopy.

Non-specific pleuritis in patients with active malignancy.

BACKGROUND AND OBJECTIVE: Pleuroscopy is the test of choice for patients with suspected malignant pleural effusion and negative cytology. Biopsies negative for malignancy are frequently attributed to non-specific pleuritis, which poses a dilemma in patients with a known active malignancy, raising concern for a false-negative result. Our primary objective was to determine the outcomes of patients with active malignancy who had a non-malignant diagnosis on pleuroscopy. METHODS: Retrospective review of all pleuroscopy cases from January 2005 to January 2015 at our institution was conducted. Biopsies were categorized by histopathology as malignant, eosinophilic or non-specific pleuritis. Malignant histopathology was considered a true positive. Eosinophilic or non-specific pleuritis was categorized as malignant, if malignancy was later identified during follow-up, or chemotherapy induced, possible radiation induced, other paramalignant, other benign or idiopathic. RESULTS: Of the 199 pleuroscopy cases reviewed, 172 (86%) had a history of active malignancy. On histopathology, 73 (42%) had malignancy, 9 (5%) had eosinophilic pleuritis and 90 (52%) had non-specific pleuritis. Three patients with non-specific pleuritis were diagnosed with malignancy at follow-up. Pleuritis in 24 patients was chemotherapy induced, 27 were possibly radiation induced, 11 were other paramalignant and 3 were other benign. Idiopathic pleuritis was diagnosed in 31 patients. Patients were monitored for a mean of 23 ± 11 months. CONCLUSION: The prevalence of malignant pleural disease was lower than expected for our patient population. Patients with no malignancy on histopathology were most likely to have non-specific pleuritis, a cause for which was identified in a majority of patients after clinical review.

Pleural Touch Preparations and Direct Visualization of the Pleura during Medical Thoracoscopy for the Diagnosis of Malignancy.

RATIONALE: During diagnostic thoracoscopy, talc pleurodesis after biopsy is appropriate if the probability of malignancy is sufficiently high. Findings on direct visual assessment of the pleura during thoracoscopy, rapid onsite evaluation (ROSE) of touch preparations (touch preps) of thoracoscopic biopsy specimens, and preoperative imaging may help predict the likelihood of malignancy; however, data on the performance of these methods are limited. OBJECTIVES: To assess the performance of ROSE of touch preps, direct visual assessment of the pleura during thoracoscopy, and preoperative imaging in diagnosing malignancy. METHODS: Patients who underwent ROSE of touch preps during thoracoscopy for suspected malignancy were retrospectively reviewed. Malignancy was diagnosed on the basis of final pathologic examination of pleural biopsy specimens. ROSE results were categorized as malignant, benign, or atypical cells. Visual assessment results were categorized as tumor studding present or absent. Positron emission tomography (PET) and computed tomography (CT) findings were categorized as abnormal or normal pleura. Likelihood ratios were calculated for each category of test result. RESULTS: The study included 44 patients, 26 (59%) with a final pathologic diagnosis of malignancy. Likelihood ratios were as follows: for ROSE of touch preps: malignant, 1.97 (95% confidence interval [CI], 0.90-4.34); atypical cells, 0.69 (95% CI, 0.21-2.27); benign, 0.11 (95% CI, 0.01-0.93); for direct visual assessment: tumor studding present, 3.63 (95% CI, 1.32-9.99); tumor studding absent, 0.24 (95% CI, 0.09-0.64); for PET: abnormal pleura, 9.39 (95% CI, 1.42-62); normal pleura, 0.24 (95% CI, 0.11-0.52); and for CT: abnormal pleura, 13.15 (95% CI, 1.93-89.63); normal pleura, 0.28 (95% CI, 0.15-0.54). CONCLUSIONS: A finding of no malignant cells on ROSE of touch preps during thoracoscopy lowers the likelihood of malignancy significantly, whereas finding of tumor studding on direct visual assessment during thoracoscopy only moderately increases the likelihood of malignancy. A positive finding on PET and/or CT increases the likelihood of malignancy significantly in a moderate-risk patient group and can be used as an adjunct to predict malignancy before pleurodesis.

Indwelling Pleural Catheters for Patients with Hematologic Malignancies. A 14-Year, Single-Center Experience.

RATIONALE: Placement of an indwelling pleural catheter is an established modality for symptom relief and pleurodesis in the treatment of malignant pleural effusion. Concerns remain regarding possible infectious complications, risk of hemorrhage, and the rate of pleurodesis with the use of pleural catheters in the treatment of hematologic malignancies. OBJECTIVES: The goals of our study were: (1) to evaluate the safety and cumulative incidence of pleurodesis with indwelling pleural catheters for patients with hematologic malignancies, and (2) to evaluate overall survival of this cohort of patients with pleural effusions. METHODS: We performed a retrospective review of 172 patients with a hematologic malignancy who underwent placement of an indwelling pleural catheter between September 1997 and August 2011 at the University of Texas MD Anderson Cancer Center in Houston, Texas. A competing risk model analysis was used for complications and pleurodesis. Analysis was based on each patient's first intrapleural catheter. RESULTS: There were 172 patients with lymphoma (58%), acute (16%) or chronic leukemia (16%), or multiple myeloma (10%). The effusions were characterized as malignant (85.5%), infectious (4.1%), volume overload (4.7%), or therapy-related (4.7%). Chylothorax was found in 20.1%. Pleural biopsies were obtained from 13 patients. The cumulative incidence of all complications was 13.6%, and the cumulative incidence of all significant catheter-related complications was 9.5%. The incidence of empyema was 2.9%, and major bleeding (requiring transfusion or intervention) was 1.7%. Thirty-day procedure-associated mortality was 0.6%. The cumulative incidence of pleurodesis at 180 days was 50%, with a median time to pleurodesis of 81 days for the entire cohort. CONCLUSIONS: Indwelling pleural catheters appear to be safe for patients with hematologic malignancies. Complications and the cumulative incidence of pleurodesis are comparable to those reported for patients with solid organ malignancies.

What Exactly Is a Centrally Located Lung Tumor? Results of an Online Survey.

RATIONALE: Accurate mediastinal staging is a cornerstone in the management of patients with lung cancer. For patients with radiographically normal mediastinum, current lung cancer guidelines recommend invasive mediastinal staging when tumors are centrally located. However, definitions of central tumors are nonspecific, and there are discrepancies among guidelines (e.g., some use the inner one-third of the hemithorax, whereas others use the inner two-thirds). OBJECTIVES: To describe the definitions of central tumors used by pulmonologists and thoracic surgeons in their practices. METHODS: An online questionnaire was e-mailed to members of the American Association for Bronchology and Interventional Pulmonology and members of the Cardiothoracic Surgery Network. MEASUREMENTS AND MAIN RESULTS: A total of 218 participants completed our survey (12% response rate). Most common definitions for central tumors were: inner one-third of the hemithorax (55%), in contact with hilar structures (29%), and inner two-thirds of the hemithorax (15%). Of note, 29% of participants chose a definition fabricated specifically for this survey and not supported by guidelines. Regarding the method to delineate the thirds of the hemithorax, 182 (84%) participants chose a system of concentric lines arising in the hilum, whereas 31 (14%) chose straight lines in the sagittal plane of the chest. We found strikingly similar responses in members of both societies. CONCLUSIONS: A uniform definition of tumor centrality is currently lacking, and should be formulated. Studies using objective measurements that evaluate the ability of these different definitions of central lung tumors to predict N2 disease are needed to construct a clear and evidence-based definition.

Intrapleural Fibrinolytic Therapy in Patients With Nondraining Indwelling Pleural Catheters.

BACKGROUND: Tissue plasminogen activator (tPA) has been successfully used to relieve obstruction of dysfunctional devices, including vascular catheters. Intrapleural tPA is used by some centers to restore flow of nondraining indwelling pleural catheters (IPCs) in symptomatic patients with malignant pleural effusions (MPEs). Because few studies have evaluated its safety and effectiveness, we conducted a retrospective cohort study of outcomes after tPA treatment during a 10-year period at our institution. METHODS: We studied 97 patients with MPE and a nondraining IPC in the setting of persistent pleural fluid who were treated with intrapleural tPA. The primary outcome was restoration of flow after treatment. Secondary outcomes included complication rates and the need for further pleural interventions. Symptomatic relief was assessed using the Borg perceived scale. RESULTS: We identified 97 patients with MPE and a nondraining IPC who were treated with tPA. Flow was restored after 1 tPA dose in 83 of 97 patients (86%; 95% confidence interval, 77%-92%). Reocclusion after 1 dose was seen in 27 of 83 patients (32%), and 22 (81%) of these patients were treated with a second tPA dose. Among these 22, flow was restored in 16 (72%; 95% confidence interval, 44%-84%). Borg score improvement was only seen in patients who had restored flow (P=0.024). This finding was independent of the size of the effusion upon chest x-ray. There were 5 complications: 2 hemothoraxes and 3 infectious complications. CONCLUSION: On the basis of our finding of successful flow restoration with few complications, we recommend intrapleural tPA treatment for symptomatic patients with nondraining IPCs in the setting of persistent pleural fluid.

Diagnostic Yield and Complications of Bronchoscopy for Peripheral Lung Lesions. Results of the AQuIRE Registry.

RATIONALE: Advanced bronchoscopy techniques such as electromagnetic navigation (EMN) have been studied in clinical trials, but there are no randomized studies comparing EMN with standard bronchoscopy. OBJECTIVES: To measure and identify the determinants of diagnostic yield for bronchoscopy in patients with peripheral lung lesions. Secondary outcomes included diagnostic yield of different sampling techniques, complications, and practice pattern variations. METHODS: We used the AQuIRE (ACCP Quality Improvement Registry, Evaluation, and Education) registry to conduct a multicenter study of consecutive patients who underwent transbronchial biopsy (TBBx) for evaluation of peripheral lesions. MEASUREMENTS AND MAIN RESULTS: Fifteen centers with 22 physicians enrolled 581 patients. Of the 581 patients, 312 (53.7%) had a diagnostic bronchoscopy. Unadjusted for other factors, the diagnostic yield was 63.7% when no radial endobronchial ultrasound (r-EBUS) and no EMN were used, 57.0% with r-EBUS alone, 38.5% with EMN alone, and 47.1% with EMN combined with r-EBUS. In multivariate analysis, peripheral transbronchial needle aspiration (TBNA), larger lesion size, nonupper lobe location, and tobacco use were associated with increased diagnostic yield, whereas EMN was associated with lower diagnostic yield. Peripheral TBNA was used in 16.4% of cases. TBNA was diagnostic, whereas TBBx was nondiagnostic in 9.5% of cases in which both were performed. Complications occurred in 13 (2.2%) patients, and pneumothorax occurred in 10 (1.7%) patients. There were significant differences between centers and physicians in terms of case selection, sampling methods, and anesthesia. Medical center diagnostic yields ranged from 33 to 73% (P = 0.16). CONCLUSIONS: Peripheral TBNA improved diagnostic yield for peripheral lesions but was underused. The diagnostic yields of EMN and r-EBUS were lower than expected, even after adjustment.

Mediastinal Granulomatous Inflammation and Overall Survival in Patients with a History of Malignancy.

RATIONALE: Investigators have postulated that mediastinal granulomatous inflammation is associated with prolonged overall survival in patients with cancer. OBJECTIVES: We sought to determine whether mediastinal granulomatous inflammation affects overall survival in patients with a history of treated cancer. METHODS: Patients with a history of treated cancer who underwent endobronchial ultrasound-transbronchial needle aspiration (EBUS-TBNA) for evaluation of mediastinal or hilar lymphadenopathy were grouped based on whether they had mediastinal granulomatous inflammation or benign mediastinal lymphadenopathy without granulomas. Overall survival from the date of EBUS-TBNA to cancer-related death or to last follow-up in patient groups was compared. MEASUREMENTS AND MAIN RESULTS: We reviewed the records of 106 patients (44 with mediastinal granulomatous inflammation and 62 with benign mediastinal lymphadenopathy). The 3-year survival rate was 90% overall and 93 and 88% in patients with mediastinal granulomatous inflammation and benign mediastinal lymphadenopathy, respectively (P=0.40). After multivariate adjustment, whether patients had mediastinal granulomatous inflammation or benign mediastinal lymphadenopathy did not significantly affect the risk of cancer death (mediastinal granulomatous inflammation to benign mediastinal lymphadenopathy hazard ratio, 1.27; P=0.76). CONCLUSIONS: These results suggest that patients who develop mediastinal granulomatous inflammation after cancer treatment do not have an increased overall survival when compared with patients who develop benign mediastinal lymphadenopathy. EBUS-TBNA is warranted for patients with treated cancer who develop mediastinal and/or hilar lymphadenopathy to avoid erroneous upstaging or misdiagnosis of cancer recurrence that would lead to suboptimal management.

Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration for the Diagnosis and Subtyping of Lymphoma.

BACKGROUND: Excisional biopsies are typically used to diagnose lymphoma, but data suggest that endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is equally effective. In this study, we determined whether EBUS-TBNA could accurately diagnose and subtype lymphoma. METHODS: The cases of patients who had undergone EBUS-TBNA for suspected lymphoma were retrospectively reviewed. EBUS-TBNA results were categorized as lymphoma, specific nonlymphoma diagnosis, granulomatous inflammation, or adequate or inadequate lymphocytes with no specific diagnosis. To quantify the ability of EBUS-TBNA to diagnose lymphoma, we used likelihood ratios. To quantify the ability of EBUS-TBNA to diagnose and subtype lymphoma, we calculated sensitivity and specificity. For this analysis, lymphoma that could be subtyped on the basis of EBUS-TBNA was classified as a true positive; lymphoma that could not be subtyped was classified as a false negative. RESULTS: Of the 181 patients included, 75 (41.5%) were ultimately diagnosed with lymphoma. EBUS-TBNA was able to establish a diagnosis of lymphoma in 63 patients (84%). Granulomatous inflammation diagnosed on the basis of EBUS-TBNA was associated with a low likelihood of lymphoma being present (likelihood ratio, 0.00; 95% confidence interval [CI], 0.00-0.276). Adequate lymphocytes were associated with a low likelihood of lymphoma (LR, 0.25; 95% CI, 0.14-0.49). EBUS-TBNA was able to establish a diagnosis and subtype the lymphoma in 67% (95% CI, 0.45-0.88) of patients with de novo lymphoma and 81% (95% CI, 0.70-0.91) of patients with relapsed lymphoma. CONCLUSIONS: EBUS-TBNA is an effective, minimally invasive diagnostic test for patients with suspected lymphoma and can provide valuable clinical information, even with "negative" results.

Complications Following Therapeutic Bronchoscopy for Malignant Central Airway Obstruction: Results of the AQuIRE Registry.

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 < .001). The overall complication rate was 3.9%, but significant variation was found among centers (range, 0.9%-11.7%; 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.

Pulmonary artery intimal sarcoma diagnosed using endobronchial ultrasound-guided transbronchial needle aspiration.

Intimal sarcoma of the pulmonary artery is a rare intraluminal malignant neoplasm that has an aggressive biological behavior, and early diagnosis may improve patient outcome. We describe a case of pulmonary artery intimal sarcoma diagnosed on cytologic material obtained by endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) biopsy with rapid on-site evaluation (ROSE). The aspirate showed loosely cohesive clusters of pleomorphic malignant spindled and epithelioid cells. An immunostain panel did not demonstrate any definitive mesenchymal or epithelial differentiation. The tumor's intraluminal origin was supported by radiographic imaging studies. Subsequently, the patient received preoperative chemotherapy and underwent tumor resection with reconstruction. This report describes the cytomorphologic features of this rare intravascular tumor and demonstrates how EBUS-TBNA with ROSE was instrumental in obtaining optimal cytologic sampling for ancillary studies, thus expediting the management.

Endobronchial ultrasound-guided transbronchial needle aspiration for systematic nodal staging of lung cancer in patients with N0 disease by computed tomography and integrated positron emission tomography-computed tomography.

RATIONALE: 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. OBJECTIVES: 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. METHODS: 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. MEASUREMENTS AND MAIN RESULTS: 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%). CONCLUSIONS: 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.

Randomized trial of endobronchial ultrasound-guided transbronchial needle aspiration under general anesthesia versus moderate sedation.

RATIONALE: Data about the influence of the type of sedation on yield, complications, and tolerance of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) are based mostly on retrospective studies and are largely inconsistent. OBJECTIVES: To determine whether the type of sedation influences the diagnostic yield of EBUS-TBNA, its complication rates, and patient tolerance. METHODS: Patients referred for EBUS-TBNA were randomized (1:1) to undergo this procedure under general anesthesia (GA) or moderate sedation (MS). Pathologists were blinded to group allocation. MEASUREMENTS AND MAIN RESULTS: The main outcome was "diagnostic yield," defined as the percentage of patients for whom EBUS-TBNA rendered a specific diagnosis. One hundred and forty-nine patients underwent EBUS-TBNA, 75 under GA and 74 under MS. Demographic and baseline clinical characteristics were well balanced. Two hundred and thirty-six lymph nodes (LNs) and six masses were sampled in the GA group (average, 3.2 ± 1.9 sites/patient), and 200 LNs and six masses in the MS group (average, 2.8 ± 1.5 sites/patient) (P = 0.199). The diagnostic yield was 70.7% (53 of 75) and 68.9% (51 of 74) for the GA group and MS group, respectively (P = 0.816). The sensitivity was 98.2% in the GA group (confidence interval, 97-100%) and 98.1% in the MS group (confidence interval, 97-100%) (P = 0.979). EBUS was completed in all patients in the GA group, and in 69 patients (93.3%) in the MS group (P = 0.028). There were no major complications or escalation of care in either group. Minor complications were more common in the MS group (29.6 vs. 5.3%) (P < 0.001). Most patients stated they "definitely would" undergo this procedure again in both groups (P = 0.355). CONCLUSIONS: EBUS-TBNA performed under MS results in comparable diagnostic yield, rate of major complications, and patient tolerance as under GA. Future prospective multicenter studies are required to corroborate our findings. Clinical trial registered with www.clinicaltrials.gov (NCT 01430962).

Therapeutic bronchoscopy for malignant central airway obstruction: success rates and impact on dyspnea and quality of life.

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.

Safety of flexible bronchoscopy, rigid bronchoscopy, and endobronchial ultrasound-guided transbronchial needle aspiration in patients with malignant space-occupying brain lesions.

BACKGROUND: Bronchoscopy in patients with space-occupying brain lesions is anecdotally felt to carry a high risk of neurologic complications. METHODS: We conducted a retrospective cohort study of patients with evidence of a malignant, space-occupying brain lesion who were referred for flexible or rigid bronchoscopy or endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA). The primary outcome of interest was the incidence of neurologic complications following the procedures in these patients. RESULTS: Of the 103 enrolled patients, flexible bronchoscopy was performed in 41, rigid bronchoscopy in 12, and EBUS-TBNA in 50. Among these patients, 41 (40%) had evidence suggestive of increased intracranial pressure on imaging. Among all study patients, none (95% CI, 0-0.035) had neurologic, procedure-specific, or sedation-specific complications, and the level of care was not escalated in any of these patients. CONCLUSIONS: On the basis of our findings, we recommend that procedures such as flexible or rigid bronchoscopy or EBUS-TBNA in patients with malignant space-occupying brain lesions should be considered reasonably safe as long as neurologic findings are stable.

Vandetanib and indwelling pleural catheter for non-small-cell lung cancer with recurrent malignant pleural effusion.

INTRODUCTION/BACKGROUND: Non-small-cell lung cancer patients with malignant pleural effusion have a poor overall median survival (4.3 months). VEGF is a key regulator of pleural effusion production. It is unknown if pharmacological inhibition of VEGF signaling modifies the disease course of non-small-cell lung cancer patients with recurrent malignant pleural effusion. We report the final results of a single-arm phase II clinical trial of the VEGF receptor inhibitor, vandetanib, combined with intrapleural catheter placement in patients with non-small-cell lung cancer and recurrent malignant pleural effusion, to determine whether vandetanib reduces time to pleurodesis. PATIENTS AND METHODS: Non-small-cell lung cancer patients with proven metastatic disease to the pleural space using pleural fluid cytology or pleural biopsy who required intrapleural catheter placement were eligible for enrollment. On the same day of the intrapleural catheter insertion, the patients were started on a daily oral dose of 300 mg vandetanib, for a maximum of 10 weeks. The primary end point was time to pleurodesis, with response rate as the secondary end point. Exploratory analyses included measurement of pleural fluid cytokines and angiogenic factors before and during therapy. RESULTS: Twenty eligible patients were included in the trial. Eleven patients completed 10 weeks of treatment. Median time to pleurodesis was 35 days (95% confidence interval, 15-not applicable). Median time to pleurodesis in the historical cohort was 63 days (95% confidence interval, 45-86) when adjusted for Eastern Cooperative Oncology Group performance status ≤ 2. CONCLUSION: Vandetanib therapy was well tolerated; however, it did not significantly reduce time to pleurodesis.

Quality-adjusted survival following treatment of malignant pleural effusions with indwelling pleural catheters.

BACKGROUND: 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. METHODS: 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. RESULTS: A total of 266 patients were enrolled. Median quality-adjusted survival was 95.1 QALDs. Dyspnea improved significantly following IPC placement (P < .001), but utility increased only modestly. Patients who had chemotherapy or radiation after IPC placement (P < .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 (P < .001) rather than to decreased drainage. CONCLUSIONS: 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. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT01117740; URL: www.clinicaltrials.gov.

Bronchoscopic findings and bleeding control predict survival in patients with solid malignancies presenting with mild hemoptysis.

BACKGROUND: Regardless of its volume, hemoptysis is a concerning symptom. Mild hemoptysis and its significance in patients with solid malignancies has not been studied. METHODS: We conducted a retrospective chart review of patients with solid malignancies who presented for evaluation of mild hemoptysis. In this population, we studied the impact of bronchoscopic findings and endobronchial therapies on overall survival and bleeding recurrence. Patients were categorized into four groups on the basis of the presence or absence of active bleeding and endobronchial disease at the time of initial bronchoscopy: active bleeding with endobronchial lesion (AB/EBL), active bleeding without endobronchial lesion (AB/no-EBL), absence of active bleeding but with endobronchial lesion (no-AB/EBL), and absence of active bleeding and endobronchial lesion (no-AB/no-EBL). MEASUREMENTS AND MAIN RESULTS: Ninety-five of the 112 patients with solid malignancies and mild hemoptysis underwent bronchoscopies. There was a significantly lower median survival time for patients with bronchoscopic findings of active bleeding and endobronchial lesion compared with patients with no active bleeding and/or no endobronchial lesion (3.48 mo; 95% confidence interval [CI], 2.14-6.05). On a multivariate analysis, factors independently associated with improved survival were higher hemoglobin values (hazard ratio [HR], 0.78; 95% CI, 0.67-0.91) and cessation of hemoptysis without recurrence at 48 hours (HR, 0.43; 95% CI, 0.22-0.84). Variables independently associated with worse survival were disease stage (HR, 10.8; 95% CI, 2.53-46.08) and AB/EBL (HR, 3.20; 95% CI, 1.74-5.89). CONCLUSIONS: In patients with solid malignancies presenting with mild hemoptysis, bronchoscopic findings of AB/EBL are associated with decreased survival. Hemoptysis control without recurrence at 48 hours after endobronchial intervention may improve survival.