Diagnosing and screening for tumors through noninvasive means represent an important paradigm shift in precision medicine. In contrast to tissue biopsy, detection of circulating tumor cells (CTCs) and circulating tumor nucleic acids provides a minimally invasive method for predictive and prognostic marker detection. This allows early and serial assessment of metastatic disease, including follow-up during remission, characterization of treatment effects, and clonal evolution. Isolation and characterization of CTCs and circulating tumor DNA (ctDNA) are likely to improve cancer diagnosis, treatment, and minimal residual disease monitoring. However, more trials are required to validate the clinical utility of precise molecular markers for a variety of tumor types. This review focuses on the clinical utility of CTCs and ctDNA testing in patients with solid tumors, including somatic and epigenetic alterations that can be detected. A comparison of methods used to isolate and detect CTCs and some of the intricacies of the characterization of the ctDNA are also provided.

BACKGROUND.To the authors' knowledge, the frequency and clinical impact of errors in the anatomic pathology diagnosis of cancer have been poorly characterized to date. METHODS.The authors examined errors in patients who underwent anatomic pathology tests to determine the presence or absence of cancer or precancerous lesions in four hospitals. They analyzed 1 year of retrospective errors detected through a standardized cytologic-histologic correlation process (in which patient same-site cytologic and histologic specimens were compared). Medical record reviews were performed to determine patient outcomes. The authors also measured the institutional frequency, cause (i.e., pathologist interpretation or sampling), and clinical impact of diagnostic cancer errors. RESULTS.The frequency of errors in cancer diagnosis was found to be dependent on the institution (P Ͻ 0.001) and ranged from 1.79 -9.42% and from 4.87-11.8% of all correlated gynecologic and nongynecologic cases, respectively. A statistically significant association was found between institution and error cause (P Ͻ 0.001); the cause of errors resulting from pathologic misinterpretation ranged from 5.0 -50.7% (the remainder were due to clinical sampling). A statistically significant association was found between institution and assignment of the clinical impact of error (P Ͻ 0.001); the aggregated data demonstrated that for gynecologic and nongynecologic errors, 45% and 39%, respectively, were associated with harm. The pairwise kappa statistic for interobserver agreement on cause of error ranged from 0.118 -0.737. CONCLUSIONS. Errors in cancer diagnosis

Rapid identification of pathogens directly from positive blood cultures can play a major role in reducing patient mortality rates. We evaluated the performance of the Verigene Gram-Positive Blood Culture (BC-GP) assay (Nanosphere Inc., Northbrook, IL) for detection of commonly isolated Gram-positive organisms as well as associated resistance markers from positive blood cultures. Positive blood cultures (VersaTREK; Trek Diagnostic Systems, Independence, OH) from 203 patients with Gram-positive organism infections were analyzed using the BC-GP assay within 12 h for the detection of 12 different organisms, including staphylococci, streptococci, and enterococci, as well as for the presence of 3 resistance markers (mecA, vanA, and vanB). Results were compared to those of routine laboratory methods for identification and susceptibility testing. For identification of organisms and detection of resistance markers in 178 monomicrobial positive blood cultures, the BC-GP assay showed 94% and 97% concordance, respectively, with routine methods. After 25 polymicrobial cultures were included, the results showed 92% and 96% agreement for identification and resistance markers, respectively, for a total of 203 positive cultures. In 6/25 polymicrobial cultures, at least 1 isolate was not detected. Concordance levels for detection of major pathogens such Staphylococcus aureus (n ‫؍‬ 45) and enterococci (n ‫؍‬ 19) were 98% and 95%, respectively. Agreement levels for detection of resistance markers such as mecA and vanA/B were 92% and 100%, respectively. The BC-GP assay is capable of providing rapid identification of Gram-positive cocci as well as detection of resistance markers directly from positive blood cultures at least 24 to 48 h earlier than conventional methods.

A pediatric predictive model for GABHS pharyngitis performed better than physicians' subjective estimates for a positive throat culture and was comparable with a rapid antigen detection test. The model performed consistently well in different populations and across seasons. It can be useful if reliable microbiological testing and/or follow-up are not attainable.

Scant published data exist on redesigning pathology practice based on error data. In this first step of an Agency for Healthcare Research and Quality patient safety project, we measured the performance metrics of thyroid gland fine-needle aspiration, performed root cause analysis to determine the causes of error, and proposed error-reduction initiatives to address specific errors. Eleven cytologists signed out 1,543 thyroid gland aspirates in 2 years, and surgical pathology follow-up was obtained in 364 patients. Of the 364 patients, 91 (25.0%) had a false-negative diagnosis and 36 (9.9%) a false-positive diagnosis. Root cause analysis showed that major sources of error were pre-analytic (poor specimen quality) and analytic (interpretation of unsatisfactory specimens as nonneoplastic and lack of diagnostic category standardization). We currently are evaluating the effectiveness of error reduction initiatives that target pre-analytic and analytic portions of the diagnostic pathway.