Optimizing clinical outcomes for bronchoscopic lung volume reduction with Zephyr® valves.

Bronchoscopic lung volume reduction treatment with Zephyr one-way valves is an effective guideline-based treatment option for patients with severe emphysema and hyperinflation. However, in some cases the treatment response is less than anticipated or there might be a loss of initial treatment effect. Reasons for the lack of response can include incorrect assessment of collateral ventilation, improper valve placement, or patient related factors. Loss of initial benefit can be due to granulation tissue formation and subsequent valve dysfunction, or there may be side effects such as excessive coughing or infectious problems. Careful follow-up after treatment with valves is important and evaluation with a CT scan and/or bronchoscopy is helpful if there is no improvement after treatment or loss of initial benefit. This paper aims to describe the most important causes and provide a strategy of how to approach and manage these patients.

Efficacy and safety of virtual bronchoscopic navigation with fused fluoroscopy and vessel mapping for access of pulmonary lesions.

BACKGROUND AND OBJECTIVE: Virtual bronchoscopic navigation (VBN) with fused fluoroscopy and vessel mapping provides a point of entry (POE) for puncturing airway wall to biopsy lesions. The study was designed to evaluate the safety and efficacy of this technology to diagnose peripheral pulmonary lesions. METHODS: It was a prospective, single-arm, multicentre study. Patients underwent lesions biopsy with the Archimedes® VBN System via a POE using one of the two techniques: (1) bronchoscopic transparenchymal nodule access (BTPNA) and (2) guided transbronchial needle aspiration (TBNA). Biopsy yield, sampling yield and diagnostic yield were mainly determined in lesions biopsy attempted. RESULTS: One hundred and thirty patients underwent anaesthesia and constituted the intention-to-treat population. One hundred and four patients with 114 lesions had biopsy attempted. Mean lesion size was 2.4 ± 1.13 cm. Sufficient tissue samples were obtained from 86 lesions with a biopsy yield of 75.4%. Nevertheless, sufficient samples for diagnosis based on histology ± cytology were obtained from 107 lesions with a sampling yield of 93.9%. Follow-up was conducted for more than 1 year, with a diagnostic yield of 75.4% and 72.8%, respectively, on high and low estimate with consideration of three lesions without follow-up. Two (1.9%) pneumothoraxes and one (1.0%) mild bleeding occurred. CONCLUSION: BTPNA and guided TBNA contribute to safe and effective sampling of peripheral pulmonary lesions. A relatively high biopsy yield was obtained independent of the presence or absence of a bronchus sign (BS), and high sampling yield and diagnostic yield were obtained independent of location, lesion size and presence or absence of a BS.

Computed tomography criteria for the use of advanced localization techniques in minimally invasive thoracoscopic lung resection.

BACKGROUND: The significant improvement of patient outcomes from minimally invasive lung surgery has led to the development of advanced lung nodule localization techniques to help manage patients with small suspicious lung nodules or to help resect patients with small pulmonary metastases. However, there are no clear computed tomography (CT) criteria to guide the use of advanced localization techniques for this group of patients. METHODS: We conducted a retrospective chart review of patients who had undergone initial wedge resection of single or multiple lung nodules. We collected demographics, surgical information and surgical outcomes as well as CT scan features. Multiple logistic regression was performed to determine which factors were most predictive of the need for advanced localization techniques. RESULTS: A total of 45 patients (73%) were resected by direct identification alone while 17 patients (27%) required advanced localization techniques. Of those requiring advanced localization, 11 patients had cone beam CT, 3 patients had transbronchial localization using electromagnetic navigation and 3 patients had preoperative CT guided wire localization. Patients requiring advanced localization had significantly smaller lung nodules at 0.8 cm compared to 1.4 cm (P=0.01), nodules that were further away from the pleura at 1.3 cm compared 0.1 cm (P<0.001) and were more likely to have ground glass nodules (P=0.01) compared to patients who were resected by direct identification alone. Multiple logistic regression confirmed that nodule size, distance to pleura and ground glass attenuation were predictive factors for requiring advanced localizing techniques. Every patient was treated with minimally invasive lung resection. A 1.3-cm or greater solitary pulmonary nodule less than 5 mm from the pleura can be removed without advanced techniques with a 96% success rate. CONCLUSIONS: Overall, in patients undergoing resection of a suspicious primary or metastatic lung nodule, advanced localization techniques should be considered in those with small non-solid nodules, which are not near the pleural surface on CT scan.

A Multicenter Randomized Controlled Trial of Zephyr Endobronchial Valve Treatment in Heterogeneous Emphysema (LIBERATE).

RATIONALE: This is the first multicenter randomized controlled trial to evaluate the effectiveness and safety of Zephyr Endobronchial Valve (EBV) in patients with little to no collateral ventilation out to 12 months. OBJECTIVES: To evaluate the effectiveness and safety of Zephyr EBV in heterogeneous emphysema with little to no collateral ventilation in the treated lobe. METHODS: Subjects were enrolled with a 2:1 randomization (EBV/standard of care [SoC]) at 24 sites. Primary outcome at 12 months was the ΔEBV-SoC of subjects with a post-bronchodilator FEV1 improvement from baseline of greater than or equal to 15%. Secondary endpoints included absolute changes in post-bronchodilator FEV1, 6-minute-walk distance, and St. George's Respiratory Questionnaire scores. MEASUREMENTS AND MAIN RESULTS: A total of 190 subjects (128 EBV and 62 SoC) were randomized. At 12 months, 47.7% EBV and 16.8% SoC subjects had a ΔFEV1 greater than or equal to 15% (P < 0.001). ΔEBV-SoC at 12 months was statistically and clinically significant: for FEV1, 0.106 L (P < 0.001); 6-minute-walk distance, +39.31 m (P = 0.002); and St. George's Respiratory Questionnaire, -7.05 points (P = 0.004). Significant ΔEBV-SoC were also observed in hyperinflation (residual volume, -522 ml; P < 0.001), modified Medical Research Council Dyspnea Scale (-0.8 points; P < 0.001), and the BODE (body mass index, airflow obstruction, dyspnea, and exercise capacity) index (-1.2 points). Pneumothorax was the most common serious adverse event in the treatment period (procedure to 45 d), in 34/128 (26.6%) of EBV subjects. Four deaths occurred in the EBV group during this phase, and one each in the EBV and SoC groups between 46 days and 12 months. CONCLUSIONS: Zephyr EBV provides clinically meaningful benefits in lung function, exercise tolerance, dyspnea, and quality of life out to at least 12 months, with an acceptable safety profile in patients with little or no collateral ventilation in the target lobe. Clinical trial registered with www.clinicaltrials.gov (NCT 01796392).

Management of the Solitary Pulmonary Nodule.

CONTEXT: - Optimal management of the patient with a solitary pulmonary nodule entails early diagnosis and appropriate treatment for patients with malignant tumors, and minimization of unnecessary interventions and procedures for those with ultimately benign nodules. With the growing number of high-resolution imaging modalities and studies available, incidentally found solitary pulmonary nodules are an increasingly common occurrence. OBJECTIVE: - To provide guidance to clinicians involved in the management of patients with a solitary pulmonary nodule, including aspects of risk stratification, workup, diagnosis, and management. DATA SOURCES: - Data for this review were gathered from an extensive literature review on the topic. CONCLUSIONS: - Logical evaluation and management pathways for a patient with a solitary pulmonary nodule will allow providers to diagnose and treat individuals with early stage lung cancer and minimize morbidity from invasive procedures for patients with benign lesions.

Next-Generation Sequencing of a Cohort of Pulmonary Large Cell Carcinomas Reclassified by World Health Organization 2015 Criteria.

CONTEXT: The classification of pulmonary large cell carcinoma has undergone a major revision with the recent World Health Organization (WHO) 2015 Classification. Many large cell carcinomas are now reassigned to either adenocarcinoma with solid pattern or nonkeratinizing squamous cell carcinoma based on immunopositivity for adenocarcinoma markers or squamous cell carcinoma markers, respectively. Large cell carcinomas that are negative for adenocarcinoma and squamous cell carcinoma immunomarkers are now classified as large cell carcinoma with null immunohistochemical features (LCC-N). Although a few studies investigated the mutation profile of large cell carcinomas grouped by immunostain profile before the publication of the new WHO classification, investigation of tumors previously diagnosed as large cell carcinoma and reclassified according to the 2015 WHO classification has not, to our knowledge, been reported. OBJECTIVE: To determine the mutation profiles of pulmonary large cell carcinomas reclassified by WHO 2015 criteria. DESIGN: Archival cases of non-small cell lung carcinoma with large cell carcinoma morphology (n = 17) were reclassified according to 2015 WHO criteria. To determine mutation profile, we employed Ion Torrent (Life Technologies, Carlsbad, California)-based next-generation sequencing (50 genes; more than 2800 mutations) in addition to real-time quantitative reverse transcription polymerase chain reaction for ALK translocation detection. RESULTS: Two of 17 cases (12%) were reclassified as LCC-N, and both had mutations-BRAF D594N in one case and KRAS G12C in the other case. Seven of 17 cases (41%) were reclassified in the adenocarcinoma with solid pattern group, which showed one KRAS G12C and one EGFR E709K + G719C double mutation in addition to mutations in TP53. Eight of 17 cases (47%) were reclassified in the nonkeratinizing squamous cell carcinoma group, which showed mutations in PIK3CA, CDKN2A, and TP53. No ALK translocations or amplifications were detected. CONCLUSIONS: The adenocarcinoma with solid pattern group showed mutations typical of adenocarcinoma, whereas the nonkeratinizing squamous cell carcinoma group showed mutations typical of squamous cell carcinoma. Both LCC-N cases had mutations associated with adenocarcinoma, supporting the hypothesis that LCC-N is related to adenocarcinoma.