Initiation and characterization of small cell lung cancer patient-derived xenografts from ultrasound-guided transbronchial needle aspirates.

Small cell lung cancer (SCLC) is a devastating disease with limited treatment options. Due to its early metastatic nature and rapid growth, surgical resection is rare. Standard of care treatment regimens remain largely unchanged since the 1980's, and five-year survival lingers near 5%. Patient-derived xenograft (PDX) models have been established for other tumor types, amplifying material for research and serving as models for preclinical experimentation; however, limited availability of primary tissue has curtailed development of these models for SCLC. The objective of this study was to establish PDX models from commonly collected fine needle aspirate biopsies of primary SCLC tumors, and to assess their utility as research models of primary SCLC tumors. These transbronchial needle aspirates efficiently engrafted as xenografts, and tumor histomorphology was similar to primary tumors. Resulting tumors were further characterized by H&E and immunohistochemistry, cryopreserved, and used to propagate tumor-bearing mice for the evaluation of standard of care chemotherapy regimens, to assess their utility as models for tumors in SCLC patients. When treated with Cisplatin and Etoposide, tumor-bearing mice responded similarly to patients from whom the tumors originated. Here, we demonstrate that PDX tumor models can be efficiently established from primary SCLC transbronchial needle aspirates, even after overnight shipping, and that resulting xenograft tumors are similar to matched primary tumors in cancer patients by both histology and chemo-sensitivity. This method enables physicians at non-research institutions to collaboratively contribute to the rapid establishment of extensive PDX collections of SCLC, enabling experimentation with clinically relevant tissues and development of improved therapies for SCLC patients.

A randomised trial of lung sealant versus medical therapy for advanced emphysema.

Uncontrolled pilot studies demonstrated promising results of endoscopic lung volume reduction using emphysematous lung sealant (ELS) in patients with advanced, upper lobe predominant emphysema. We aimed to evaluate the safety and efficacy of ELS in a randomised controlled setting.Patients were randomised to ELS plus medical treatment or medical treatment alone. Despite early termination for business reasons and inability to assess the primary 12-month end-point, 95 out of 300 patients were successfully randomised, providing sufficient data for 3- and 6-month analysis.57 patients (34 treatment and 23 control) had efficacy results at 3 months; 34 (21 treatment and 13 control) at 6 months. In the treatment group, 3-month lung function, dyspnoea, and quality of life improved significantly from baseline when compared to control. Improvements persisted at 6 months with >50% of treated patients experiencing clinically important improvements, including some whose lung function improved by >100%. 44% of treated patients experienced adverse events requiring hospitalisation (2.5-fold more than control, p=0.01), with two deaths in the treated cohort. Treatment responders tended to be those experiencing respiratory adverse events.Despite early termination, results show that minimally invasive ELS may be efficacious, yet significant risks (probably inflammatory) limit its current utility.

Cryobiopsy: should this be used in place of endobronchial forceps biopsies?

UNLABELLED: Forceps biopsies of airway lesions have variable yields. The yield increases when combining techniques in order to collect more material. With the use of cryotherapy probes (cryobiopsy) larger specimens can be obtained, resulting in an increase in the diagnostic yield. However, the utility and safety of cryobiopsy with all types of lesions, including flat mucosal lesions, is not established. AIMS: Demonstrate the utility/safety of cryobiopsy versus forceps biopsy to sample exophytic and flat airway lesions. SETTINGS AND DESIGN: Teaching hospital-based retrospective analysis. METHODS: Retrospective analysis of patients undergoing cryobiopsies (singly or combined with forceps biopsies) from August 2008 through August 2010. Statistical Analysis. Wilcoxon signed-rank test. RESULTS: The comparative analysis of 22 patients with cryobiopsy and forceps biopsy of the same lesion showed the mean volumes of material obtained with cryobiopsy were significantly larger (0.696 cm(3) versus 0.0373 cm(3), P = 0.0014). Of 31 cryobiopsies performed, one had minor bleeding. Cryopbiopsy allowed sampling of exophytic and flat lesions that were located centrally or distally. Cryobiopsies were shown to be safe, free of artifact, and provided a diagnostic yield of 96.77%. CONCLUSIONS: Cryobiopsy allows safe sampling of exophytic and flat airway lesions, with larger specimens, excellent tissue preservation and high diagnostic accuracy.