Rabih Bechara

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).

Validation of an Interventional Pulmonary Examination

BACKGROUND Interventional pulmonology (IP) is an emerging subspecialty with a dedicated 12 months of additional training after traditional pulmonary and critical care fellowships with fellowships across the country. A multiple-choice question (MCQ) examination was developed to measure didactic knowledge acquired in IP fellowships. METHODS Interventional pulmonologists from 10 academic centers developed a MCQ-based examination on a proposed curriculum for IP fellowships. The 75 multiple-choice question examination was proctored, time limited (120 min), and computer-based. The examination was administered to IP faculty, IP fellows in their last month of fellowship, graduating pulmonary and critical care fellows in their last month of training, and incoming first-year pulmonary and critical care fellows. RESULTS The mean score for IP faculty was 87% (range, 83%-94%), 74% for IP fellows (range, 61%-81%, SD 5.09, median 76%), 62% for graduating pulmonary and critical care fellows (range 52% to 73%), and 50% for incoming pulmonary/critical care fellows (range, 35%-65%). There was a graduated increase in mean scores with level of IP training. Scores differed significantly across the four groups (P = .001). CONCLUSION A validated MCQ examination can measure IP knowledge. There is a difference in IP knowledge based on IP training exposure.

Effect of routine clopidogrel use on bleeding complications after ultrasound-guided thoracentesis.

Background:Thoracentesis is one of the most commonly performed medical procedures with an excellent safety profile. Clopidogrel (a compound that inhibits adenosine diphosphate–induced platelet aggregation) is often prescribed for primary or secondary prevention of cardiovascular disease and has been associated with bleeding complications in patients undergoing surgical procedures. The purpose of this study was to assess the safety of ultrasound (US)-guided thoracentesis in patients receiving clopidogrel therapy. Methods:Data were collected on 30 consecutive patients taking clopidogrel without other known underlying coagulation problems. These patients underwent 45 US-guided thoracenteses over 26 months. Clopidogrel was not discontinued before the thoracentesis in patients presenting with symptomatic pleural effusion. Thoracenteses were performed in these patients and the incidence of bleeding and other complications among patients was reported. Results:Between June 2009 and August 2011, there were 30 consecutive patients on clopidogrel at the time of thoracenteses. These patients presented with respiratory distress because of pleural effusion and underwent a total of 45 thoracenteses. There was no significant bleeding or other complications in this patient population. No patient required transfusion after the procedure. Conclusion:Patients who are receiving clopidogrel and present with symptomatic pleural effusion can safely undergo US-guided thoracentesis without interrupting clopidogrel before the procedure. Larger studies are required to confirm these results.

Electromagnetic navigation bronchoscopy

In 2009, lung cancer was estimated to be the second most common form of cancer diagnosed in men, after prostate, and the second, after breast cancer, in women. It is estimated that it caused 159,390 deaths more than breast, colon and prostate cancers combined. While age-adjusted death rates for this cancer have been declining since 2000, they remain high.

A Translational, Pharmacodynamic, and Pharmacokinetic Phase IB Clinical Study of Everolimus in Resectable Non-Small Cell Lung Cancer.

Purpose: The altered PI3K/mTOR pathway is implicated in lung cancer, but mTOR inhibitors have failed to demonstrate efficacy in advanced lung cancer. We studied the pharmacodynamic effects of everolimus in resectable non–small cell lung cancer (NSCLC) to inform further development of these agents in lung cancer. Experimental Design: We enrolled 33 patients and obtained baseline tumor biopsy and 2[18F]fluoro-2-deoxy-D-glucose-positron emission tomography/computed tomography (FDG-PET/CT) imaging followed by everolimus treatment (5 or 10 mg daily, up to 28 days), or without intervening treatment for controls. Target modulation by everolimus was quantified in vivo and ex vivo by comparing metabolic activity on paired PET scans and expression of active phosphorylated forms of mTOR, Akt, S6, eIF4e, p70S6K, 4EBP1, and total Bim protein between pretreatment and posttreatment tissue samples. Results: There were 23 patients on the treatment arm and 10 controls; median age 64 years; 22 tumors (67%) were adenocarcinomas. There was a dose-dependent reduction in metabolic activity (SUVmax: 29.0%, −21%, −24%; P = 0.014), tumor size (10.1%, 5.8%, −11.6%; P = 0.047), and modulation of S6 (−36.1, −13.7, −77.0; P = 0.071) and pS6 (−41.25, −61.57, −47.21; P = 0.063) in patients treated in the control, 5-mg, and 10-mg cohorts, respectively. Targeted DNA sequencing in all patients along with exome and whole transcriptome RNA-seq in an index patient with hypersensitive tumor was employed to further elucidate the mechanism of everolimus activity. Conclusions: This “window-of-opportunity” study demonstrated measurable, dose-dependent, biologic, metabolic, and antitumor activity of everolimus in early-stage NSCLC. Clin Cancer Res; 21(8); 1859–68. ©2015 AACR.

Comparative cost analysis of endobronchial ultrasound-guided and blind TBNA in the evaluation of hilar and mediastinal lymphadenopathy.

Background:The superior accuracy of endobronchial ultrasound (EBUS) averts many diagnostic surgical procedures. This likely leads to significant cost savings despite an increased per procedure cost. We sought to compare the true costs of endobronchial ultrasound-transbronchial needle aspiration (EBUS-TBNA) compared with “blind” fiberoptic bronchoscopy-transbronchial needle aspiration (FB-TBNA) factoring in the impact of diagnostic surgical procedures in the diagnosis of mediastinal lymphadenopathy. Methods:In this retrospective case study, we selected 294 patients with thoracic lymphadenopathy as diagnosed by computed tomography at a university hospital. Information was extracted from the electronic record. Costs were determined from the Centers for Medicare and Medicaid Services resource-based relative value scale. We defined a positive diagnosis as one where benign or malignant disease was found. A negative biopsy was one where lymph node sampling was confirmed, but no pathology (benign or malignant) was seen. A nondiagnostic biopsy was one where no pathology was seen and lymph node sampling could not be confirmed. The total cost of endoscopic and surgical diagnostic procedures was tallied for each patient to obtain mean costs per patient. Results:Thirty-seven patients underwent FB-TBNA and 257 underwent EBUS-TBNA. A diagnosis was found in 90% of patients in the EBUS group and 62.2% of patients in the FB-TBNA group (P<0.001). More patients in the FB-TBNA group underwent a diagnostic surgical procedure (HR= −0.1573, 95% confidence interval, −0.30 to −0.15; P<0.001). After accounting for all diagnostic procedures, the mean savings with EBUS was

Central intranodal vessels to predict cytology during endobronchial ultrasound transbronchial needle aspiration.

1071.09 (P=0.09) per patient. Conclusions:EBUS-TBNA is less expensive than blind FB-TBNA in the evaluation of thoracic lymphadenopathy when accounting for diagnostic surgical procedures.

Point-of-Care Ultrasound in the Intensive Care Unit

Background:There has been recent interest in identifying the endoscopic ultrasonographic characteristics of lymph nodes (LNs) that predict the presence or absence of malignant involvement. Normal LN anatomy includes the presence of a central intranodal blood vessel (CIV) that can be obliterated with invasion of malignant cells. We sought to determine whether examining LNs for the presence or absence of a CIV during endobronchial ultrasound (EBUS) could predict benign or malignant cytology of the samples obtained. Methods:We prospectively evaluated patients undergoing EBUS-transbronchial needle aspiration (TBNA) for mediastinal or hilar adenopathy in a tertiary care referral center. All LNs were prospectively characterized as having or not having a CIV and subsequently classified as benign or malignant by cytologic analysis. Results:A total of 56 patients undergoing EBUS-TBNA were evaluated. One hundred three LNs were available for analysis. Fifty-six of 103 LNs were positive for malignancy (54.3%). Ultrasonographic identification of a CIV was associated with benign LN cytology with a sensitivity of 83.0% and a specificity of 91.1% and an OR of 49.7 (95% confidence interval, 15.1-163.9). Finding a CIV had a positive predictive value for benign LN cytology of 88.6%. The absence of finding a CIV had a positive predictive value for malignant cytology of 86.4%. The presence or absence of a CIV had an overall diagnostic accuracy of 87.4% (correctly categorizing 90 of 103 LNs). Conclusions:There are morphologic characteristics of LNs that can be visualized at the time of EBUS to help predict whether the nodes being evaluated have malignant involvement. The presence of a CIV suggests that the node is benign, whereas the absence of a central intranodal vessel increases the likelihood of malignancy. The presence or absence of a CIV has a good overall accuracy in predicting malignancy (87.4%).

Mediastinal and Hilar Lymph Node Measurements. Comparison of Multidetector-Row Computed Tomography and Endobronchial Ultrasound

Spreading beyond the realm of tertiary academic medical centers, point-of-care ultrasound in the intensive care unit is an important diagnostic tool. The real-time feedback garnered can lead to critical and clinically relevant changes in management and decrease potential complications. Bedside ultrasound evaluation in the intensive care setting with a small, portable equipment is well-suited for placement of central lines, lumbar puncture, thoracentesis or other bedside ICU procedures and in the evaluation of cardiac activity, pleural and abdominal cavity and the overall fluid volume. Formalized curriculums centering on point-of-care ultrasound are emerging that will enhance its applicability and relevance.

The use of transtracheal oxygen therapy in the management of severe hepatopulmonary syndrome after liver transplantation.

RATIONALE Multidetector-row chest computed tomography scan is a common initial imaging modality and endobronchial ultrasound is a minimally invasive diagnostic tool used to evaluate enlarged lymph nodes, but comparisons of imaging results are lacking. OBJECTIVES To determine the size of thoracic lymph nodes and the strength of agreement between each measurement from coronal plane computed tomography and static endobronchial ultrasound images. METHODS A retrospective review of consecutive patients who underwent endobronchial ultrasound-transbronchial needle aspiration of their lymph nodes because of clinical suspicion of benign or malignant thoracic disease. MEASUREMENTS AND MAIN RESULTS One hundred and twenty-four lymph nodes from the mediastinal (74.2%) and hilar (25.8%) stations were measured in 59 patients (mean age, 64.5 yr; 33 males). The mean (standard deviation) short-axis diameter on computed tomography was 14.1 (6.7) mm compared with 12.6 (6.6) mm on endobronchial ultrasound. Benign lymph nodes (n = 42) were larger on computed tomography than on endobronchial ultrasound (14.1 [6.2] vs. 11.5 [6.2] mm). Malignant lymph nodes (n = 35) were larger on endobronchial ultrasound than on computed tomography (17.3 [6.4] vs. 16.2 [6.7] mm). Sixty-five percent of the lymph nodes that were initially interpreted as not enlarged on axial computed tomography images measured greater than 10 mm on each imaging modality (12.5 [5.9] mm on computed tomography and 10.5 [5.6] mm on endobronchial ultrasound) and 24% of the sampled lymph nodes from this group contained malignant cells. Random-effects maximal likelihood linear regression showed a statistically significant difference between endobronchial ultrasound and the computed tomography method for measuring short-axis diameter in all 124 lymph nodes. There was a weak agreement (intraclass correlation, rho: 0.44 [95% confidence interval, 0.31-0.59]) between short-axis diameter measurements from each imaging modality. CONCLUSIONS Our single-center study shows that there was poor correlation between computed tomography and endobronchial ultrasound for the measurement of mediastinal and hilar lymph nodes. Malignant cells were recovered by ultrasound-guided needle aspiration from a substantial fraction of lymph nodes that were initially interpreted as normal in size. If these findings are confirmed, new criteria may be needed for lymph node measurement on computed tomography that will guide selection of lymph nodes for endobronchial ultrasound-transbronchial needle aspiration.