Rapid KRAS, EGFR, BRAF and PIK3CA Mutation Analysis of Fine Needle Aspirates from Non-Small-Cell Lung Cancer Using Allele-Specific qPCR

Endobronchial Ultrasound Guided Transbronchial Needle Aspiration (EBUS-TBNA) and Trans-esophageal Ultrasound Scanning with Fine Needle Aspiration (EUS-FNA) are important, novel techniques for the diagnosis and staging of non-small cell lung cancer (NSCLC) that have been incorporated into lung cancer staging guidelines. To guide and optimize treatment decisions, especially for NSCLC patients in stage III and IV, EGFR and KRAS mutation status is often required. The concordance rate of the mutation analysis between these cytological aspirates and histological samples obtained by surgical staging is unknown. Therefore, we studied the extent to which allele-specific quantitative real-time PCR with hydrolysis probes could be reliably performed on EBUS and EUS fine needle aspirates by comparing the results with histological material from the same patient. We analyzed a series of 43 NSCLC patients for whom cytological and histological material was available. We demonstrated that these standard molecular techniques can be accurately applied on fine needle cytological aspirates from NSCLC patients. Importantly, we show that all mutations detected in the histological material of primary tumor were also identified in the cytological samples. We conclude that molecular profiling can be reliably performed on fine needle cytology aspirates from NSCLC patients

Endosonography for lung cancer staging: predictors for false-negative outcomes

Non-small cell lung cancer (NSCLC) guidelines recommend endosonography (endobronchial [EBUS] and/or transesophageal ultrasound [EUS]) as the initial step for mediastinal tissue staging. Identifying predictors for false negative results could help establish which patients should undergo confirmatory surgical staging. 775 NSCLC patients staged negative by EBUS, EUS or combined EUS/EBUS were retrospectively analyzed. Predictors of false-negative outcomes were identified by logistic regression analysis. Three predictors for false-negative outcomes were identified: central location of the lung tumor (OR 3.7/4.5/3.6 for EBUS, EUS and EUS/EBUS respectively, p <0.05), nodal enlargement on CT (OR 3.2/2.5/4.9 for EBUS, EUS and EUS/EBUS respectively, p <0.05) and FDG-avidity of N2/N3 lymph node stations on PET (OR 4.2/4.0/7.5 for EBUS, EUS and EUS/EBUS respectively, p <0.05). One subgroup (peripheral lung tumor, nodal enlargement on CT without FDG-avidity for N2/N3) had a low predicted probability (7.8%) for false-negative EUS. For combined EUS/EBUS, two subgroups were identified: peripheral located tumor with nodal enlargement on CT but without FDG-avidity for N2/N3 (predicted probability 4.7%) and centrally located tumor without affected lymph nodes on CT or PET (predicted probability 3.4%). In conclusion, for specific well-defined subsets of NSCLC patients the low predicted probability of metastasis after negative endosonography might justify omitting confirmatory surgical stagin

Anomalous coronary artery from the pulmonary artery diagnosed in adulthood: a case series on variations of coronary anatomy and the diagnostic value of cardiac magnetic resonance imaging

BACKGROUND: Anomalous coronary artery from the pulmonary artery is a rare congenital disorder with high mortality rates in infancy. Adult cases can present with life-threatening arrhythmias and sudden cardiac death. CASE SUMMARY: We report three cases of adults with anomalous pulmonary origin of each of the main coronary branches. The first patient with an anomalous left coronary artery from the pulmonary artery presented with an out-of-hospital cardiac arrest. The second patient with an anomalous circumflex artery from the pulmonary artery was evaluated for a bicuspid aortic valve and a suspected coronary fistula but was otherwise asymptomatic. The third patient with an anomalous right coronary artery from the pulmonary artery presented with anginal symptoms. In all cases, the diagnosis was made by cardiac computed tomography or coronary angiography. Cardiac magnetic resonance imaging was performed in all patients to guide clinical decision making on surgical or non-invasive management. All patients underwent surgical repair. In two patients, a dual coronary artery system was restored by aortic reimplantation of the anomalous coronary artery. In one patient, aortic reimplantation was unsuccessful due to poor vessel quality and the anomalous coronary artery was ligated. Clinical follow-up during 1.8-9.7 years did not show any cardiovascular complications and all patients are currently alive and asymptomatic. DISCUSSION: Anomalous coronary artery from the pulmonary artery can have various clinical presentations in adulthood. Cardiac magnetic resonance imaging is a useful modality to guide selection of patients who might have symptomatic or prognostic benefit from surgical repair