Hans J. Lee

Optimizing Endobronchial Ultrasound for Molecular Analysis. How Many Passes Are Needed

BACKGROUND The current oncologic management of non-small cell lung cancer (NSCLC) requires pathologic differentiation between adenocarcinoma and squamous cell carcinoma. Furthermore, novel therapies for adenocarcinoma are clinically available for specific mutation profiles. Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) has been shown to adequately obtain specimens for molecular profiling. However, it remains unclear what quantity of specimens is needed to provide suitable mutational genotyping for adenocarcinoma. The objective of this study was to determine the optimal number of aspirations per EBUS-TBNA procedure required in the presence of rapid on-site cytopathology evaluation (ROSE) for maximal diagnostic yield for molecular mutational analysis. METHODS From March 2010 to February 2012, cytopathologic data were collected from consecutive cases of adenocarcinoma or NSCLC not otherwise specified (NSCLC-NOS), diagnosed by EBUS-TBNA and ROSE. Samples of material obtained were air-dried and wet-fixed. Samples were tested for the KRAS, EGFR, and/or ALK mutations. MEASUREMENTS AND MAIN RESULTS Eighty-five patients who underwent EBUS-TBNA and were diagnosed with adenocarcinoma or NSCLC-NOS were identified. Of the 85 cases identified, 77 (90.6%) were classified as adenocarcinoma with the remaining 8 (9.4%) classified as NSCLC-NOS. Eighty-one of 85 (95.3%) were found to be adequate for molecular profiling. The median number of sites sampled was one. A median of four passes was needed to obtain adequate molecular profiling of 95.3%, using EBUS in conjunction with ROSE. CONCLUSIONS With the use of EBUS-TBNA and ROSE, a minimum of four needle passes may provide an adequate amount of specimen for advanced molecular marker analysis.

Comparison of Moderate versus Deep Sedation for Endobronchial Ultrasound Transbronchial Needle Aspiration

RATIONALE Most bronchoscopic procedures are performed using moderate sedation achieved by combining a short-acting benzodiazepine with an opioid agent. Propofol (2.6-diisopropylphenol), a short-acting hypnotic agent, has been increasingly used to provide deep sedation in the endoscopy community with an acceptable safety profile. OBJECTIVES To compare the impact of moderate versus deep sedation on the adequacy and diagnostic yield of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA). METHODS A retrospective review of prospectively collected data was performed at two academic institutions with interventional pulmonary fellowships using two methods of sedation during EBUS (deep vs. moderate sedation). Rapid on-site cytologic evaluation was used on all procedures in both groups. EBUS-TBNA nodal sampling was considered adequate if the aspirate yielded a specific diagnosis or lymphocytes. EBUS-TBNA was considered diagnostic if a lymph node aspirate yielded a specific diagnosis or if subsequent surgical sampling or prolonged radiographic surveillance revealed no nodal pathology. MEASUREMENTS AND MAIN RESULTS No difference was observed in the indication for EBUS-TBNA between the two groups. More lymph nodes were sampled per patient in the deep sedation group (314 nodes from 163 patients; 2.2 nodes per patient) than in the moderate sedation group (181 lymph nodes from 146 patients; 1.4 nodes per patient; P < 0.01). The EBUS-TBNA diagnostic yield was higher for the deep sedation group (80% of patients) than for the moderate sedation group (66% of patients; P < 0.01). CONCLUSIONS Diagnostic yield and number of lymph nodes sampled using deep sedation is superior to moderate sedation in patients undergoing EBUS-TBNA. Prospective studies accounting for other factors including patient selection and cost are needed.

Randomized Trial of Pleural Fluid Drainage Frequency in Patients with Malignant Pleural Effusions. The ASAP Trial

Rationale: Patients with malignant pleural effusions have significant dyspnea and shortened life expectancy. Indwelling pleural catheters allow patients to drain pleural fluid at home and can lead to autopleurodesis. The optimal drainage frequency to achieve autopleurodesis and freedom from catheter has not been determined. Objectives: To determine whether an aggressive daily drainage strategy is superior to the current standard every other day drainage of pleural fluid in achieving autopleurodesis. Methods: Patients were randomized to either an aggressive drainage (daily drainage; n = 73) or standard drainage (every other day drainage; n = 76) of pleural fluid via a tunneled pleural catheter. Measurements and Main Results: The primary outcome was the incidence of autopleurodesis following the placement of the indwelling pleural catheters. The rate of autopleurodesis, defined as complete or partial response based on symptomatic and radiographic changes, was greater in the aggressive drainage arm than the standard drainage arm (47% vs. 24%, respectively; P = 0.003). Median time to autopleurodesis was shorter in the aggressive arm (54 d; 95% confidence interval, 34‐83) as compared with the standard arm (90 d; 95% confidence interval, 70 to nonestimable). Rate of adverse events, quality of life, and patient satisfaction were not significantly different between the two arms. Conclusions: Among patients with malignant pleural effusion, daily drainage of pleural fluid via an indwelling pleural catheter led to a higher rate of autopleurodesis and faster time to liberty from catheter. Clinical trial registered with www.clinicaltrials.gov (NCT 00978939).

Interventional Pulmonology Fellowship Accreditation Standards: Executive Summary of the Multisociety Interventional Pulmonology Fellowship Accreditation Committee

&NA; 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.

The Use of Indwelling Tunneled Pleural Catheters for Recurrent Pleural Effusions in Patients With Hematologic Malignancies: A Multicenter Study

BACKGROUND Malignant pleural effusion is a common complication of advanced malignancies. Indwelling tunneled pleural catheter (IPC) placement provides effective palliation but can be associated with complications, including infection. In particular, hematologic malignancy and the associated immunosuppressive treatment regimens may increase infectious complications. This study aimed to review outcomes in patients with hematologic malignancy undergoing IPC placement. METHODS A retrospective multicenter study of IPCs placed in patients with hematologic malignancy from January 2009 to December 2013 was performed. Inclusion criteria were recurrent, symptomatic pleural effusion and an underlying diagnosis of hematologic malignancy. Records were reviewed for patient demographics, operative reports, and pathology, cytology, and microbiology reports. RESULTS Ninety-one patients (mean ± SD age, 65.4 ± 15.4 years) were identified from eight institutions. The mean × SD in situ dwell time of all catheters was 89.9 ± 127.1 days (total, 8,160 catheter-days). Seven infectious complications were identified, all of the pleural space. All patients were admitted to the hospital for treatment, with four requiring additional pleural procedures. Two patients died of septic shock related to pleural infection. CONCLUSIONS We present, to our knowledge, the largest study examining clinical outcomes related to IPC placement in patients with hematologic malignancy. An overall 7.7% infection risk and 2.2% mortality were identified, similar to previously reported studies, despite the significant immunosuppression and pancytopenia often present in this population. IPC placement appears to remain a reasonable clinical option for patients with recurrent pleural effusions related to hematologic malignancy.

Intrapleural fibrinolysis for the treatment of indwelling pleural catheter-related symptomatic loculations: A multicenter observational study

BACKGROUND Indwelling pleural catheters (IPCs) are an effective option in the management of malignant pleural effusion. Up to 14% of patients with IPCs develop symptomatic pleural loculations causing ineffective fluid drainage and breathlessness. To our knowledge, this is the first study to describe intrapleural fibrinolytic therapy for IPC-related symptomatic loculations. METHODS All patients who received intrapleural fibrinolytic therapy for symptomatic loculations between January 1, 2002, and June 30, 2014, in four established IPC centers were retrospectively included. Patient outcomes, treatment effectiveness, and adverse events were recorded. RESULTS Sixty-six patients (mean age, 64.7 ± 14.2 years; 52% women) were included. Lung cancer (31.3%) and malignant pleural mesothelioma (20.3%) were the most common malignancies. Fibrinolytic instillation was performed in outpatient (61%) and inpatient settings. Tissue-plasminogen activator (n = 52), urokinase (n = 12), and streptokinase (n = 2) were used. The majority (69.7%) received only one fibrinolytic dose (range, one to six). Pleural fluid drainage increased in 93% of patients, and dyspnea improved in 83% following therapy. The median cumulative pleural fluid volume drained at 24 h posttreatment was 500 mL (interquartile range 300-1,034 mL). The area of opacity caused by pleural effusion on chest radiograph decreased from (mean, SD) 52% (14%) to 31% (21%) of the hemithorax (n = 13; P = .001). There were two cases of nonfatal pleural bleed (3%). CONCLUSIONS Intrapleural fibrinolytic therapy can improve pleural fluid drainage and symptoms in selected patients with IPC and symptomatic loculation, but it carries a small risk of pleural bleeding. There is significant heterogeneity in its use currently, and further studies are needed to determine patient selection and optimal dosing regimen and to define its safety profile.

Novel bronchoscopic strategies for the diagnosis of peripheral lung lesions: Present techniques and future directions

The diagnosis of the peripheral lung lesion has been a long‐standing clinical challenge—balancing accuracy with patient safety. With recent data revealing mortality benefits with lung cancer screening via low‐dose computed tomography, now more than ever, clinicians will be challenged with the task of providing the means to provide a safe and minimally invasive method of obtaining accurate tissue diagnostics for the pulmonary nodule. In this review, we present available technologies to aid clinicians in attempts at minimally invasive techniques and the data supporting their use. In addition, we review novel tools under investigation that may further increase yield and provide additional benefit in obtaining an early diagnosis of lung cancer.

The use of convex probe endobronchial ultrasound-guided transbronchial needle aspiration in a pediatric population: A multicenter study

The presence of intrathoracic lymphadenopathy and mediastinal masses in the pediatric population often presents a diagnostic challenge. With limited minimally invasive methodologies to obtain a diagnosis, invasive sampling via mediastinoscopy or thoracotomy is often pursued. Endobronchial ultrasound transbronchial needle aspiration (EBUS‐TBNA) is a minimally invasive, outpatient procedure that has demonstrated significant success in the adult population in the evaluation of such abnormalities. Within the pediatric literature there is limited data regarding the use of EBUS‐TBNA. We report the first multicenter review of a pediatric population undergoing EBUS‐TBNA procedures identifying the feasibility, safety, utility, and outcomes of this procedure.

Airway Complications Following Lung Transplantation

There are 6 major types of airway complications following lung transplantation: necrosis and dehiscence, infection, granulation tissue formation, malacia, fistulae, and stenosis. This article reviews the risk factors for developing airway complications after lung transplantation, the clinical features of the complications, and treatment options for these problems.

Use of One-Way Intrabronchial Valves in Air Leak Management after Tube Thoracostomy Drainage

BACKGROUND A persistent air leak represents significant clinical management problems, potentially affecting morbidity, mortality, and health care costs. In 2008, a unidirectional, intrabronchial valve received humanitarian device exemption for use in managing prolonged air leak after pulmonary resection. Since its introduction, numerous reports exist but no large series describe current utilization or outcomes. Our aim was to report current use of intrabronchial valves for air leaks and review outcome data associated with its utilization. METHODS A multicenter, retrospective review of intrabronchial valve utilization from January 2013 to August 2014 was performed at eight centers. Data regarding demographics, valve utilization, and outcomes were analyzed. RESULTS We identified 112 patients undergoing evaluation for intrabronchial valve placement, with 67% (75 of 112) undergoing valve implantation. Nearly three quarters of patients underwent valve placement for off-label usage (53 of 75). A total of 195 valves were placed in 75 patients (mean 2.6 per patient; range, 1 to 8) with median time to air leak resolution of 16 days (range, 2 to 156). CONCLUSIONS We present the largest, multicenter study of patients undergoing evaluation for intrabronchial valve use for air leak management. Our data suggest the majority of intrabronchial valve placements are occurring for off-label indications. Although the use of intrabronchial valves are a minimally invasive intervention for air leak management, the lack of rigorously designed studies demonstrating efficacy remains concerning. Prospective randomized controlled studies remain warranted.