Pharmacokinetics and safety of paclitaxel delivery into porcine airway walls by a new endobronchial drug delivery catheter.

BACKGROUND AND OBJECTIVE: Intratumoral administration of chemotherapeutic agents is a treatment modality that has proven efficacious in reducing the recurrence of tumours and increases specificity of treatment while minimizing systemic side effects. Direct intratumoral injection of malignant airway obstruction has potential therapeutic benefits but tissue drug concentrations and side-effect profiles are poorly understood. METHODS: Bronchial wall injection of generic paclitaxel (PTX) (102 injections of 0.05, 0.5, 1.5 or 2.5 mg/mL in 10 healthy pigs), saline (14 injections in 2 healthy pigs) or Abraxane (ABX) (24 injections of 0.5 mg/mL in 4 healthy pigs) was performed with a microneedle infusion catheter. Local histopathology, plasma and tissue PTX concentrations were evaluated at 7, 20 or 28 days post-injection. RESULTS: Injection of generic PTX directly into the bronchial wall at doses up to 1.5 mg/mL only caused minimal tissue injury. Dose-limiting tissue reaction was observed at 2.5 mg/mL. Plasma PTX was detectable for up to 5 days but not at 28 days, with area under the curve (AUC)(0-5d) 20- to 50-fold lower than the AUC(0-∞) of 6300 ng h/mL for the approved intravenous dose. At 7 and 28 days post-injection, bronchial PTX tissue concentrations were above a 10-nmol/L cancer therapeutic level. PTX was not found in peripheral tissues. Similar results were observed between ABX and generic PTX. CONCLUSION: Results of these studies confirm the administration of PTX directly into the bronchial wall is safe and feasible. PTX was detectable in plasma for <7 days but tissue concentrations remained therapeutic throughout the follow-up period.

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.

Target lobe volume reduction and COPD outcome measures after endobronchial valve therapy.

Endobronchial valve (EBV) therapy may be associated with improvements in chronic obstructive pulmonary disease-related outcomes and may therefore be linked to improvements in the body mass index, airflow obstruction, dyspnoea, exercise capacity (BODE) index. Data from 416 patients with advanced emphysema and hyperinflation across Europe and USA, who were randomised to EBV (n=284) or conservative therapy (n=132) were analysed. Quantitative image analysis was used to compare the volume of the targeted lobe at baseline and at 6 months to determine target lobe volume reduction (TLVR). 44% of patients receiving EBV therapy (versus 24.7% of controls) had clinically significant improvements in the BODE index (p<0.001). BODE index was significantly reduced by mean ± sd 1.4 ± 1.8, 0.2 ± 1.3 and 0.1 ± 1.3 points in patients with TLVR >50%, 20%-50% and <20%, respectively (intergroup differences p<0.001), but increased by 0.3 ± 1.2 points in controls. Changes in BODE were predicted by baseline BODE and correlated significantly with lobar exclusion and lung volumes at 6 months. A greater proportion of patients in the treatment group than in the control group achieved a clinically meaningful improvement in BODE index; however, the likelihood of benefit was less than half in both groups. Patients in whom TLVR was obtained had greater improvements in clinical outcomes.

Pneumothorax following endobronchial valve therapy and its impact on clinical outcomes in severe emphysema.

BACKGROUND: Patients who achieve significant target lobe volume reduction (TLVR) following endobronchial valve (EBV) treatment may experience substantial improvements in clinical outcome measures. However, in cases of rapid TLVR, the risk of pneumothorax increases due to parenchymal rupture of the adjacent untreated lobe. Target lobe collapse may be more likely in EBV-treated patients who have low collateral ventilation. OBJECTIVES: The aim of this study was to evaluate the impact of pneumothorax on outcome following EBV treatment. METHODS: Data from three prospective clinical trials (the US and European cohorts of VENT and the Multicenter Chartis study) were retrieved for the analysis. All patients had undergone chest X-ray within 24 h of EBV implantation to explore the presence of pneumothorax. TLVR was assessed at either 30 (Chartis study) or 180 days (VENT), and clinical outcome measures (forced expiratory volume in 1 s (FEV1), St. George's Respiratory Questionnaire (SGRQ) and 6-min-walk distance (6-MWD)) were assessed 180 days after implantation. RESULTS: The overall rate of pneumothorax following valve therapy was 5.9% (25/421). Among these patients, 68% had a prolonged air leak for >7 days. However, patients who experienced a pneumothorax benefitted from EBV therapy, with a mean TLVR of 65% (n = 20). The mean percent change in FEV1 was 15 ± 15%, and the mean change in SGRQ was -7 ± 12 points. CONCLUSIONS: Although pneumothorax is a complication of EBV placement, it does not appear to have a negative impact on clinical outcome in terms of FEV1 and health-related quality of life.

A randomized study of endobronchial valves for advanced emphysema.

BACKGROUND: Endobronchial valves that allow air to escape from a pulmonary lobe but not enter it can induce a reduction in lobar volume that may thereby improve lung function and exercise tolerance in patients with pulmonary hyperinflation related to advanced emphysema. METHODS: We compared the safety and efficacy of endobronchial-valve therapy in patients with heterogeneous emphysema versus standard medical care. Efficacy end points were percent changes in the forced expiratory volume in 1 second (FEV1) and the 6-minute walk test on intention-to-treat analysis. We assessed safety on the basis of the rate of a composite of six major complications. RESULTS: Of 321 enrolled patients, 220 were randomly assigned to receive endobronchial valves (EBV group) and 101 to receive standard medical care (control group). At 6 months, there was an increase of 4.3% in the FEV1 in the EBV group (an increase of 1.0 percentage point in the percent of the predicted value), as compared with a decrease of 2.5% in the control group (a decrease of 0.9 percentage point in the percent of the predicted value). Thus, there was a mean between-group difference of 6.8% in the FEV1 (P=0.005). Roughly similar between-group differences were observed for the 6-minute walk test. At 12 months, the rate of the complications composite was 10.3% in the EBV group versus 4.6% in the control group (P=0.17). At 90 days, in the EBV group, as compared with the control group, there were increased rates of exacerbation of chronic obstructive pulmonary disease (COPD) requiring hospitalization (7.9% vs. 1.1%, P=0.03) and hemoptysis (6.1% vs. 0%, P=0.01). The rate of pneumonia in the target lobe in the EBV group was 4.2% at 12 months. Greater radiographic evidence of emphysema heterogeneity and fissure completeness was associated with an enhanced response to treatment. CONCLUSIONS: Endobronchial-valve treatment for advanced heterogeneous emphysema induced modest improvements in lung function, exercise tolerance, and symptoms at the cost of more frequent exacerbations of COPD, pneumonia, and hemoptysis after implantation. (Funded by Pulmonx; ClinicalTrials.gov number, NCT00129584.)

The localized inflammatory response to bronchoscopic thermal vapor ablation.

BACKGROUND: Bronchoscopic thermal vapor ablation (BTVA) reduces lung volumes in emphysema patients by inducing a localized inflammatory response (LIR) leading to a healing process of fibrosis, but may also increase symptoms. OBJECTIVES: We sought to evaluate whether the clinical manifestation of LIR correlated with patient outcome. METHODS: Respiratory adverse events and inflammatory markers were analyzed from a multicenter trial of BTVA in patients with upper-lobe-predominant emphysema. End points including changes in forced expiratory flow (FEV1), lobar volume, St. George's Respiratory Questionnaire (SGRQ), modified Medical Research Council (mMRC) and 6-minute-walk distance (6-MWD) were analyzed according to the presence or absence of a respiratory adverse event requiring treatment with an antibiotic or steroid. RESULTS: Forty-four patients received BTVA. Increases of inflammatory markers were observed with a peak between the second and fourth week. Eighteen respiratory adverse events occurred in 16 patients within 30 days of BTVA, requiring antibiotics and/or steroids. These patients had significantly greater lobar volume reduction (65.3 vs. 33.4%, p = 0.007) and a change in residual volume at 12 months (-933 vs. 13 ml, p < 0.001) associated with a greater improvement of exercise capacity and health-related quality of life than patients without respiratory adverse events. CONCLUSION: Patients with more prominent respiratory symptoms in the first 30 days following BTVA experience greater efficacy. The clinical manifestations of the LIR are predictive of long-term clinical benefits.

Bronchoscopic thermal vapour ablation therapy in the management of heterogeneous emphysema.

The need for a less invasive procedure than surgical lung volume reduction that can produce consistent improvements with reduced morbidity remains a medical goal in patients with emphysema. We sought to determine the effect of bronchoscopic thermal vapour ablation (BTVA) on lung volumes and outcomes in patients with emphysema. 44 patients with upper lobe-predominant emphysema were treated unilaterally with BTVA. Entry criteria included: age 40-75 yrs, forced expiratory volume in 1 s (FEV(1)) 15-45% predicted, previous pulmonary rehabilitation and a heterogeneity index (tissue/air ratio of lower lobe/upper lobe) from high-resolution computed tomography (HRCT) ≥ 1.2. Changes in FEV(1), St George's Respiratory Questionnaire (SGRQ), 6-min walk distance (6 MWD), modified Medical Research Council (mMRC) dyspnoea score, and hyperinflation were measured at baseline, and 3 and 6 months post-BTVA. At 6 months, mean ± SE FEV(1) improved by 141 ± 26 mL (p<0.001) and residual volume was reduced by 406 ± 113 mL (p<0.0001). SGRQ total score improved by 14.0 ± 2.4 points (p<0.001), with 73% improving by ≥ 4 points. Improvements were observed in 6 MWD (46.5 ± 10.6 m) and mMRC dyspnoea score (0.9 ± 0.2) (p<0.001 for both). Lower respiratory events (n=11) were the most common adverse event and occurred most often during the initial 30 days. BTVA therapy results in clinically relevant improvements in lung function, quality of life and exercise tolerance in upper lobe predominant emphysema.

Efficacy predictors of lung volume reduction with Zephyr valves in a European cohort.

The Endobronchial Valve for Emphysema Palliation Trial (VENT) was a multi-centre, prospective, randomised, controlled trial conducted to evaluate the safety and effectiveness of unilateral endobronchial valve (EBV) treatment. The purpose of this analysis was to assess outcomes in the previously unreported European VENT study cohort. Patients with advanced emphysema were randomly assigned (2:1) to receive Zephyr® (Pulmonx Inc., Redwood City, CA, USA) EBV treatment (n = 111) or medical management (n = 60). At 6 months, EBV patients demonstrated a significant improvement compared with the controls for mean ± SD change in forced expiratory volume in 1 s (7 ± 20% versus 0.5 ± 19%; p = 0.067), cycle ergometry (2 ± 14 W versus -3 ± 10 W; p = 0.04) and St George's Respiratory Questionnaire (-5 ± 14 points versus 0.3 ± 13 points; p = 0.047). At 12 months, the magnitude of the difference between groups for change from baseline was of similar magnitude to the differences seen at 6 months. Rates for complications did not differ significantly. EBV patients with computed tomography (CT) scans suggestive of complete fissure and lobar occlusion had a mean ± SD lobar volume reduction of -80 ± 30% and >50% met minimal clinical difference thresholds. The degree of emphysema heterogeneity did not preclude excellent outcomes. Unilateral lobar volume reduction using EBV treatment is safe and superior clinical results correlated with CT suggestive of complete fissures and successful lobar occlusion. Emphysema heterogeneity was not critical for determining positive outcomes.

Efficacy of bronchoscopic thermal vapor ablation and lobar fissure completeness in patients with heterogeneous emphysema.

BACKGROUND: Bronchoscopic thermal vapor ablation (BTVA) ablates emphysematous tissue through a localized inflammatory response followed by contractive fibrosis and tissue shrinkage leading to lung volume reduction that should not be influenced by collateral ventilation. OBJECTIVES: To determine the correlation of clinical data from a trial of BTVA with fissure integrity visually assessed by computed tomography (CT). METHODS: We conducted a single-arm study of patients with upper lobe-predominant emphysema (n = 44). Patients received BTVA either to the right upper lobe or left upper lobe, excluding the lingula. Primary efficacy outcomes were forced expiratory volume in 1 s (FEV(1)) and St. George's Respiratory Questionnaire (SGRQ) at 6 months. Lobar volume reduction from CT was another efficacy outcome measurement. The fissure of the treated lobe was analyzed visually on preinterventional CT. Incompleteness of the small fissure, the upper half of the right large fissure and the whole left large fissure were estimated visually in 5% increments, and the relative amount of fissure incompleteness was calculated. Pearson correlation coefficients were calculated for the association between fissure incompleteness and change in efficacy outcomes (baseline to 6 months) of BTVA. RESULTS: A total of 38 out of 44 patients (86%) had incompleteness in the relevant fissure. Calculated relevant fissure incompleteness was a mean of 13% of fissure integrity (range 0-63). Correlation coefficients for the association of incompleteness with outcomes were as follows: FEV(1) = 0.17; lung volume reduction = -0.27; SGRQ score = -0.10; 6-min walk distance = 0.0; residual volume (RV) = -0.18, and RV/total lung capacity = -0.14. CONCLUSIONS: Lobar fissure integrity has no or minimal influence on BTVA-induced lung volume reduction and improvements in clinical outcomes.

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.

Bronchial collapsibility at forced expiration in healthy volunteers: assessment with multidetector CT.

PURPOSE: To assess forced-expiratory bronchial collapsibility in healthy volunteers by using multidetector computed tomography (CT) and to compare the results with the current diagnostic criterion for bronchomalacia. MATERIALS AND METHODS: The institutional review board approved this HIPAA-compliant study. Following informed consent, 51 healthy volunteers with normal pulmonary function and no history of smoking were imaged by using a 64-detector row scanner with spirometric monitoring at total lung capacity and during forced exhalation. The total study population (in whom both main bronchi were imaged) included 25 men and 26 women (mean age, 50 years). Each scan was analyzed at a workstation by a fellowship-trained thoracic radiologist. Cross-sectional area measurements were obtained from end-inspiratory and forced-expiratory CT images for the right main bronchus (RMB), left main bronchus, (LMB), and bronchus intermedius (BI), and the mean percentage of expiratory collapse was calculated for each bronchus. The number of participants who exceeded the current diagnostic threshold level (>50% expiratory reduction in cross-sectional area) for bronchomalacia was calculated. Comparisons of airway dimensions and airway collapse according to bronchial segment and sex were made by using repeated-measures analysis of variance. RESULTS: Mean percentage of expiratory collapse was 66.9% ± 19.0 (standard deviation) for the RMB and 61.4% ± 16.7 for the LMB. Thirty-seven (73%) of 51 participants exceeded the diagnostic threshold level for bronchomalacia. Significant differences were observed in mean percentage of expiratory collapse between the RMB (66.9% ± 19.0) and LMB (61.4% ± 16.7) (P = .0005). Among a subgroup of 37 participants in whom the BI was also imaged, the mean percentage of expiratory collapse was 61.8% ± 22.8, and 27 (73%) participants exceeded the diagnostic threshold level for bronchomalacia. CONCLUSION: Healthy volunteers demonstrate a wide range of forced-expiratory bronchial collapse, frequently exceeding the current diagnostic threshold level for bronchomalacia.

Emerging technologies for the thorax: indications, management and complications.

The field of interventional pulmonology has rapidly expanded to include the management and treatment of complex diseases of the chest. The management of central airway obstruction, pleural disease diagnosis, treatment and palliation, advanced bronchoscopic techniques to aid in the diagnosis of lung cancer and innovative therapies to treat asthma and COPD have all emerged over the past decade. As astute clinicians, we are all aware of the risks and benefits of using these therapies to treat our patients. In order to appropriately treat and manage these often complex medical situations, the physician should have an expert knowledge of all available modalities, the expertise to safely perform the procedure and the ability to minimize the risk of and manage the associated complications that may arise. In this chapter we review and update some of the bronchoscopic and pleural interventions offered by interventional pulmonologists as well as the associated complications and management.

Endoscopic lung volume reduction.

Chronic obstructive pulmonary disease (COPD) is a category of diseases characterized by chronic airflow obstruction and hyperinflation. The GOLD committee and the American Thoracic Society/European Respiratory Society have published detailed, evidence-based reviews of management approaches, providing stepped-care algorithms for pharmacologic and nonpharmacologic therapy. Over the past several decades, much effort was spent in designing additional nonpharmacologic approaches to ameliorate symptoms in these patients. Three endoscopic lung volume reduction principles have shown promise and reached later-stage clinical trials in patients with heterogeneous emphysematous diseases. These include so-called blocking devices (valves), nonblocking devices (coils) and irreversible nonblocking techniques (bronchoscopic thermal vapor ablation, polymeric lung volume reduction) designed to collapse and remodel hyperinflated lung. For homogeneous diseases the formation of airway bypass tracts designed to facilitate emptying of damaged lung regions with long expiratory times is being investigated.

Comparison of suction catheter versus forceps biopsy for sampling of solitary pulmonary nodules guided by electromagnetic navigational bronchoscopy.

BACKGROUND: Electromagnetic navigation has been approved for use as an adjunct to standard bronchoscopy. The diagnostic yield varies depending on the size of the lesion and successful navigation to the lesion. OBJECTIVES: The performance of two different biopsy tools, i.e. catheter aspiration and forceps biopsy, in the diagnosis of small pulmonary nodules (SPN) guided by electromagnetic navigational bronchoscopy (ENB) was examined. METHODS: 54 patients referred for suspected lung cancer underwent ENB and 55 SPN (<3 cm) were sampled using both techniques. Endobronchial ultrasound (EBUS) was used to verify the accuracy of target lesion localization by ENB. Primary end points of the study were successful navigation to the lesion and a positive diagnosis. Patients were followed until a definitive diagnosis was obtained. RESULTS: All 55 lesions were accessed. Two lesions were excluded from data analysis as the patients were lost to follow-up and their diagnoses could not be confirmed. Of the remaining 53 lesions, 40 samples (75.5%) were diagnostic. Compared to forceps biopsy, catheter aspiration was positively correlated with the success rate (36/40 vs. 22/40; p = 0.035). The diagnostic yield was 93% when EBUS verified the lesion location after navigation and only 48% when lesion location was not confirmed. There were no significant complications. CONCLUSIONS: ENB is a useful tool in the evaluation of SPN <3 cm in diameter. For malignant lesions, sampling by catheter aspiration is associated with a higher diagnostic yield than sampling by forceps biopsy alone, in particular when EBUS could not confirm lesion location prior to sampling.

Comparison of transbronchial lung biopsy yield between standard forceps and electrocautery hot forceps in swine.

BACKGROUND: Transbronchial lung biopsy (TBLB) is a commonly performed bronchoscopic procedure. Previous studies have suggested that larger biopsy forceps may improve diagnostic yield; however, the risk of bleeding associated with larger samples may be increased. The hot forceps are large forceps that are connected to an electrocautery system to minimize bleeding at the time of biopsy. OBJECTIVES: We evaluated the hot forceps for improvement in biopsy size and the number of sampled alveoli. METHODS: TBLBs were performed in 2 swine using one type of the forceps, followed by the other forceps 24 h later. Electrocautery was applied from closure of the forceps to retrieval of the sample. A blinded pathologist measured the size of each sample in its longest dimension and calculated the total alveolar content within the largest cross-section from each biopsy. RESULTS: A total of 74 biopsies were collected using each forceps type. Alveolar tissue was present in 25/74 and 26/74 of the biopsies using the hot and conventional forceps, respectively. There was no difference in the size of biopsies collected (2.10 +/- 1.10 vs. 1.83 +/- 0.94 mm; p = 0.164) or in the amount of alveoli per sample (343.2 +/- 402.4 vs. 439.5 +/- 463.5 alveoli; p = 0.433) for hot and conventional forceps, respectively. There was no artifact related to the use of electrocautery, and bleeding was minimal using either forceps system. CONCLUSIONS: The use of the electrocautery hot forceps for TBLB did not result in improvement of the size of biopsies or the amount of collected alveolar tissue in healthy pigs.

Tracheal collapsibility in healthy volunteers during forced expiration: assessment with multidetector CT.

PURPOSE: To assess forced expiratory tracheal collapsibility in healthy volunteers by using multidetector computed tomography and to compare the results with the current diagnostic criterion for tracheomalacia. MATERIALS AND METHODS: An institutional review board approved this HIPAA-compliant study. After informed consent was obtained, 51 healthy volunteers (age range, 25-75 years) with normal spirometry results and no history of smoking or risk factors for tracheomalacia were prospectively studied. Volunteers were imaged with a 64-detector row scanner, with spirometric monitoring at total lung capacity and during forced exhalation, with 40 mAs, 120 kVp, and 0.625-mm detector collimation. Cross-sectional area and sagittal and coronal diameters of the trachea were measured 1 cm above the aortic arch and 1 cm above the carina. The percentage of expiratory collapse, the reduction in sagittal and coronal diameters, and the number of participants exceeding the current diagnostic criterion (>50% expiratory reduction in cross-sectional area) for tracheomalacia were calculated. RESULTS: The final study population included 25 men and 26 women (mean age, 50 years). The mean percentage of expiratory reduction in tracheal lumen cross-sectional area was 54.34% +/- 18.6 (standard deviation) in the upper trachea and 56.14% +/- 19.3 in the lower trachea. Forty (78%) participants exceeded the current diagnostic criterion for tracheomalacia in the upper and/or lower trachea. Decreases in cross-sectional area of the upper and lower trachea correlated well with decreases in sagittal (r = 0.807 and 0.688, respectively) and coronal (r = 0.779 and 0.751, respectively) diameters (P < .001 for each correlation). CONCLUSION: Healthy volunteers demonstrate a wide range of forced expiratory tracheal collapse, frequently exceeding the current diagnostic criterion for tracheomalacia.

Restaging of the mediastinum.

PURPOSE OF REVIEW: Patients diagnosed with stage IIIA lung cancer because of N2 positive disease are generally considered to have a short survival. However, recent studies have shown that patients who are downstaged via neoadjuvant therapy and subsequently undergo resection may have a significant increased 5-year survival rate (as high as 40-50%) when compared with patients who have residual N2 disease. The identification of patients who are N2 negative after the completion of their neoadjuvant therapy is a critical component of proper patient selection and counseling for thoracotomy and resection, especially if a pneumonectomy needs to be considered. RECENT FINDINGS: The question, how to reassess patients with stage IIIA non-small-cell lung cancer after neoadjuvant therapy, is broader than just looking at downstaging of mediastinal lymph nodes, but also involves prediction of partial or complete pathologic response on the primary tumor and long-term outcome prediction. On the basis of the published data every technique has indications and limitations. The comparison of the different techniques is still problematic for various reasons. SUMMARY: In this article we review the best ways to restage patients with N2 disease after they have completed their neoadjuvant therapy.

Vibration response imaging in the detection of pleural effusions: a feasibility study.

BACKGROUND: Computerized analysis of the regional distribution of breath sound intensity during respiration has generated interest as a possible diagnostic modality. OBJECTIVES: We hypothesized that pleural effusions would create a dependent region of absent breath sounds and thus vibration response imaging (VRI) could be used in the detection of such pleural effusions. METHODS: A prospective, single-blinded and open-labeled trial was carried out, and VRI recordings were compared to upright chest X-rays, bedside ultrasound examinations and volume of fluid drained via thoracentesis. VRI images were interpreted by a physician who was blinded to the patients' clinical history, physical examination and diagnostic tests. Quantitative assessment of pleural effusion size in the VRI images was performed by ImageJ software and an automatic pixel count analysis. RESULTS: VRI recordings were performed on 57 consecutive patients and correctly predicted the diagnosis in 45 cases (45/56, 80%) as compared to chest X-rays. The calculated sensitivity, specificity, positive predictive value and negative predictive value for diagnosis of pleural effusion were 86% (62/72), 93% (37/40), 95% (62/65) and 79% (37/47), respectively, in a per-hemithorax analysis. In the quantification of effusion size, there were high correlations between VRI images and chest X-ray area as assessed by ImageJ (r = 0.67) and pixel count (r = -0.77). The level of agreement between VRI readings and ultrasonography was 75% (41/55), and correlation with the volume of fluid drained in therapeutic thoracentesis was moderate (r = -0.49). No side effects from the VRI recordings were documented. CONCLUSIONS: VRI can be used to detect and quantify pleural effusions.

Endobronchial ultrasound-guided transbronchial needle aspiration of lymph nodes in the radiologically and positron emission tomography-normal mediastinum in patients with lung cancer.

Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) can reliably sample enlarged mediastinal lymph nodes in patients with non-small cell lung cancer (NSCLC), and in practice is mostly used to sample nodes visible on CT or positron emission tomography (PET). Few data are available on the use of endoscopic procedures to stage the mediastinum in clinical stage 1 lung cancer. The aim of the present study was to determine the results of EBUS-TBNA in sampling mediastinal lymph nodes in patients with lung cancer and a radiographically normal mediastinum and no PET activity. From January 2004 to May 2007, patients highly suspicious for NSCLC with CT scans showing no enlarged lymph nodes (no node > 1 cm) and a negative PET finding of the mediastinum underwent EBUS-TBNA. Identifiable lymph nodes at locations 2r, 2L, 4r, 4L, 7, 10r, 10L, 11r, and 11L were aspirated. All patients underwent subsequent surgical staging. Diagnoses based on aspiration results were compared with those based on surgical results. One hundred patients (mean age, 52.4 years; 59 men) were included. After surgery, 97 patients (mean age, 52.9 years; 57 men) had NSCLC confirmed and were included in the analysis. In this group, 156 lymph nodes ranging 5 to 10 mm in size were detected and sampled. Malignancy was detected in nine patients but missed in one patient. Mean diameter of the punctured lymph nodes was 7.9 mm. The sensitivity of EBUS-TBNA for detecting malignancy was 89%, specificity was 100%, and the negative predictive value was 98.9%. No complications occurred. In conclusion, EBUS-TBNA can be used to accurately sample and stage patients with clinical stage 1 lung cancer and no evidence of mediastinal involvement on CT and PET. Potentially operable patients with no signs of mediastinal involvement may benefit from presurgical staging with EBUS-TBNA.

Prospective risk-adjusted morbidity and mortality outcome analysis after therapeutic bronchoscopic procedures: results of a multi-institutional outcomes database.

INTRODUCTION: Interest in databases is growing to allow for outcomes research, assess health-care quality, and determine best practices and resource allocation, and they are increasingly considered as a tool to potentially tie reimbursement to outcome parameters. Little is known about resource use and risk-adjusted morbidity and mortality after therapeutic bronchoscopic interventions. METHODS: Data were extracted and reviewed from an ongoing prospective, multi-institutional outcomes database for therapeutic bronchoscopic interventions. All consecutive patients are entered into this database, and information on demographics, indications, procedures and anesthesia, comorbidities and general health status, urgency of intervention, morbidity and mortality to 30 days, increase in levels of care, and procedural resources is documented. RESULTS: From December 2005 to May 2007, 554 therapeutic procedures were performed in four hospitals. Most procedures were done under general anesthesia (n = 362) and rigid bronchoscopy (n = 483), and the most common intervention was airway stent placement (n = 258). Forty-two percent of procedures were done urgently or emergently. Complications were common (19.8%), and 30-day mortality was 7.8%, correlating with underlying health status and urgency of intervention. DISCUSSION: Prospective and ongoing data analysis for bronchoscopic procedures is feasible and valuable. Risk-adjusted and disease-specific outcomes can be documented and potentially used for quality assessment, benchmarking, and quality improvement initiatives. Appropriate use of resources and effect of interventions can be documented. Extending the number of participating centers as well as inclusion of quality of life tools and technical success are the next steps.