Citations

BACKGROUNDMultigene molecular testing to guide personalized therapy for oncology patients is of increasing clinical relevance. Molecular testing of fine‐needle aspiration samples is underused, but when acquired with minimally invasive techniques could become the standard of care to obtain theranostic specimens. The aims of the current study were to identify key cytology specimen selection criteria suitable for next‐generation sequencing (NGS) and to determine the prevalence and spectrum of pathogenic alterations in a cohort of patients with AJCC stage IV lung cancer.METHODSA total of 70 adrenal gland cytology specimens with direct smears were screened to identify 56 patients with a single slide containing at least 300 total cells and 20% tumor nuclei. After DNA extraction, the NGS protocols were used to simultaneously detect mutations in >2800 exonic regions in 50 key cancer genes.RESULTSA total of 28 specimens produced acceptable NGS results. Specimens with a combined critical cell mass (>5000 viable cells) and a DNA concentration >5 ng/µL resulted in a 95% chance of successful sequencing. A total of 37 pathogenic alterations were identified in 10 genes and in 25 patients (85%). A pathogenic alteration (≥1) linked to available or developing targeted therapies was revealed in 50% of cases.CONCLUSIONSThe data from the current study demonstrate that theranostic NGS can be applied to adrenal gland metastasis using routine cytologic smear specimens. The characteristics of such smears could be evaluated during onsite adequacy assessment by cytopathology professionals. This model greatly augments the opportunity for customized genotype‐directed therapy from minimally invasive techniques. Cancer (Cancer Cytopathol) 2014;122:822–832. © 2014 American Cancer Society.

Objectives Debriefing is a common feature of technology‐enhanced simulation ( TES ) education. However, evidence for its effectiveness remains unclear. We sought to characterise how debriefing is reported in the TES literature, identify debriefing features that are associated with improved outcomes, and evaluate the effectiveness of debriefing when combined with TES . Methods We systematically searched databases, including MEDLINE , EMBASE and Scopus, and reviewed previous bibliographies for original comparative studies investigating the use of TES with debriefing in training health care providers. Reviewers, in duplicate, evaluated study quality and abstracted information on instructional design, debriefing and outcomes. Effect sizes ( ES ) were pooled using random‐effects meta‐analysis. Results From 10 903 potentially eligible studies, we identified 177 studies (11 511 learners) that employed debriefing as part of TES . Key characteristics of debriefing (e.g. duration, educator presence and characteristics, content, structure/method, timing, use of video) were usually incompletely reported. A meta‐analysis of four studies demonstrated that video‐assisted debriefing has negligible and non‐significant effects for time skills ( ES = 0.10) compared with non‐video‐assisted debriefing. Meta‐analysis demonstrated non‐significant effects in favour of expert modelling with short debriefing in comparison with long debriefing (ES range = 0.21–0.74). Among studies comparing terminal with concurrent debriefing, results were variable depending on outcome measures and the context of training (e.g. medical resuscitation versus technical skills). Eight additional studies revealed insight into the roles of other debriefing‐related factors (e.g. multimedia debriefing, learner‐led debriefing, debriefing duration, content of debriefing). Among studies that compared simulation plus debriefing with no intervention, pooled ES s were favourable for all outcomes (ES range = 0.28–2.16). Conclusions Limited evidence suggests that video‐assisted debriefing yields outcomes similar to those of non‐video‐assisted debriefing. Other debriefing design features show mixed or non‐significant results. As debriefing characteristics are usually incompletely reported, future debriefing research should describe all the key debriefing characteristics along with their associated descriptors.

Background— The incidence and impact of clinical stroke and silent radiographic cerebral infarction complicating open surgical aortic valve replacement (AVR) are poorly characterized. Methods and Results— We performed a prospective cohort study of subjects ≥65 years of age who were undergoing AVR for calcific aortic stenosis. Subjects were evaluated by neurologists preoperatively and postoperatively and underwent postoperative magnetic resonance imaging. Over a 4-year period, 196 subjects were enrolled at 2 sites (mean age, 75.8±6.2 years; 36% women; 6% nonwhite). Clinical strokes were detected in 17%, transient ischemic attack in 2%, and in-hospital mortality was 5%. The frequency of stroke in the Society for Thoracic Surgery database in this cohort was 7%. Most strokes were mild; the median National Institutes of Health Stroke Scale was 3 (interquartile range, 1–9). Clinical stroke was associated with increased length of stay (median, 12 versus 10 days; P =0.02). Moderate or severe stroke (National Institutes of Health Stroke Scale ≥10) occurred in 8 (4%) and was strongly associated with in-hospital mortality (38% versus 4%; P =0.005). Of the 109 stroke-free subjects with postoperative magnetic resonance imaging, silent infarct was identified in 59 (54%). Silent infarct was not associated with in-hospital mortality or increased length of stay. Conclusions— Clinical stroke after AVR was more common than reported previously, more than double for this same cohort in the Society for Thoracic Surgery database, and silent cerebral infarctions were detected in more than half of the patients undergoing AVR. Clinical stroke complicating AVR is associated with increased length of stay and mortality.

BACKGROUNDThe cytologic diagnosis of urothelial carcinoma (UC) of the upper urothelial tract (UT) is challenging. Using the UroVysion probe set adds diagnostic value for the detection of bladder cancer in voided urine. In instrumented UT specimens, the authors encountered positive UT cytology and fluorescence in situ hybridization (FISH) cases that did not demonstrate subsequent UT carcinoma.METHODSThe performance of cytology and FISH in the presence or absence of concomitant bladder cancer within 2 years was compared in 61 patients (112 samples) from 2003 through 2009. The mean follow‐up was 3.2 years. The authors also compared the performance of near‐tetrasomy versus hypertetrasomy. Biopsy confirmation of UTUC in 21 patients was considered the gold standard.RESULTSCytology alone was found to be poorly sensitive (38%) but highly specific (89%) for the detection of UTUC. FISH was found to increase the sensitivity of cytology and decrease specificity. Tetrasomy FISH resulted in many false‐positive cases. Other false‐positive FISH results were likely due to the presence of bladder cancer cells contaminating the UT specimen.CONCLUSIONSCaution should be used when evaluating instrumented urine specimens of the UT from patients with a previous history of bladder carcinoma, and tetrasomy FISH results should not be interpreted as abnormal because it significantly lowers the specificity of the test. The combination of cytology and FISH appears to have good specificity while maintaining good sensitivity in evaluating UTUC when using modified scoring criteria for the appropriate patient population. Cancer (Cancer Cytopathol) 2014;122:459–467. © 2014 American Cancer Society.