Linear endobronchial ultrasound was first described in 2003. Since then the technique has spread rapidly and has now become an established practice in many centres as the first-line mediastinal investigation for the diagnosis and staging of lung cancer. In combination with endoscopic ultrasound, the majority of the mediastinum can be assessed and this approach has been shown to have equivalent accuracy to surgical staging. This strategy is also cost-effective. New tissue processing techniques using liquid-based thin-layer cytology and cell blocks have increased diagnostic yield using immunohistochemical staining and molecular diagnostics. Several meta-analyses of case series and, more recently, randomised controlled trials have provided high-level evidence of efficacy leading to incorporation into national lung cancer staging guidelines. In addition, linear endobronchial ultrasound is increasingly used in the investigation of mediastinal lymphadenopathy for suspected sarcoidosis, tuberculosis and lymphoma. While undoubtedly endobronchial/endoscopic ultrasound has reduced the need for surgical staging in lung cancer, the latter still has an important role to play in certain scenarios. The challenge now facing clinicians is to learn to apply the appropriate test or sequence of tests in each patient while ensuring that operators are appropriately trained in order to ensure optimal outcomes.
With the advent of multi-detector computed tomography, the identification of solitary pulmonary nodules is becoming ever more common. Although the prevalence of malignancy in a high risk population is only 1-1.5%, accurate identification of malignant nodules is essential to allow optimal treatment. In this article we review the most common causes of solitary pulmonary nodules and discuss diagnostic algorithms as well as some of the novel diagnostic imaging techniques in development.
Selective autophagy is a housekeeping energy-generating cytosolic process through which organelles and protein aggregates are tagged within a double-membrane autophagosome and delivered to the lysosome for proteolysis releasing amino acids and generating ATP. The molecular mechanisms underlying protein selection for degradation and ubiquitin complex formation within the cytosol are yet to be elucidated.The authors describe a novel molecular process through a series of experiments using bone marrow-derived macrophages infected with wild-type Mycobacterium tuberculosis (MTB). They demonstrate that MTB possesses a pore-forming enzyme system ESX-1 that exposes the MTB-containing vacuole to the cytosol. The exposure of mycobacterial DNA attracts ubiquitin and ubiquitin-binding cytosolic receptors, p62 and NADP52, through activation of the DNA-sensing STING pathway. This recruits the protein LC3 that forms puncta within the autophagosome marking it for fusion with the lysosome. They were able to demonstrate that this process is driven by MTB DNA, that bacteria targeted are killed within phagolysosomes and that this is essential for in vivo control of MTB infection-demonstrated by a fall in the number of colony-forming units within 6 h and 24 h post-infection.The work sheds new light on the processes through which MTB is cleared within macrophages, adding to the growing interest over the last decade on the cellular mechanisms underlying autophagy. It paves the way for the molecular pathways underlying MTB resistance to be elucidated and in turn identify appropriate targets for therapeutic intervention.
TBNA histology specimens using both 21G and 22G needles in confirmed primary lung adenocarcinoma. Methods A prospective analysis was performed on 250 consecutive patients undergoing EBUS-TBNA between 2009 and 2013. 21G or 22G needles (Olympus ViziShot, NA-201SX-4021 and NA-201SX-4022) were used by operator discretion. A minimum of 2 passes were carried out per nodal station. Samples were fixed in formalin and prepared for histopathological analysis. The proportion of confirmed primary lung adenocarcinoma samples in which EGFR mutation testing was feasible was determined. Results Primary lung adenocarcinoma was confirmed in 45 patients (18%). EGFR mutation analysis was attempted in 35 of these patients and was possible in 34 (97.1%). EGFR mutation was present in 3 patients (8.8%). Conclusions This single centre study demonstrates both 22G and 21G EBUS-TBNA samples are adequate for EGFR mutation analysis with no clear superiority in contrast to recent data suggesting disease phenotyping may be superior using a 21G needle when analysed by histopathology. We speculate that higher sample usability rates for mutation analysis may have been facilitated by the use of histological specimens however further larger studies are required to confirm this hypothesis. M12 EBUS-ARE TWO NEEDLES BETTER THAN ONE?WA Khan, S Bailey, M Najib; Manchester Royal Infirmary, Manchester, England 10. 1136/thoraxjnl-2013-204457.422 Introduction The introduction of endobronchial ultrasound has allowed visual sampling of nodes compared to the previous blind TBNA techniques. It was widely been used for patients with suspected lung. The purpose of our current study was to evaluate the usefulness of using a 2 needle technique compared to a single needle method in ebus sampling. The primary endpoint was to see the effect on the total number of biopsy passes, time between needle exchange and also total time taken to complete an ebus procedure. Method 20 patients with mediastinal and hilar lymphadenopathy or suspected lung cancer in our institution were included in this prospective study. EBUS-TBNA was performed in all cases. 10 procedures were used using a 2 needle technique and 10 procedures were performed with single needle. Two trained bronchoscopists with 2 trained nurses performing the needle exchange and on site cytopathologist were present at the bronchoscopy giving an instant preliminary diagnosis.Equal numbers of procedures were performed by each of the operators. Results EBUS-TBNA was successfully performed in all 20 patients recruited. In the single needle technique the average number biopsy passes performed was 3.8 per ebus with an average needle changeover delay of 2 minutes 21 seconds and an average ebus time of 27 minutes. The two needle technique showed a greater number biopsy passes of 4.4 per ebus with a significantly reduced changeover needle time delay of 18 seconds per changeover and a reduction in overall ebus time to 21 minutes per procedure. All the procedures were uneventful without complications. All sample were labe...
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