Citations

Abstract Background: Up to 70% of patients with non–muscle-invasive bladder cancer (NMIBC) experience disease recurrence, making it one of the most prevalent cancers in the United States. The purpose of this study was to test the performance of a multiplex urinary biomarker assay for the monitoring of voided urine for recurrent bladder cancer. Methods: This retrospective, multicenter study included a total of 125 subjects with a history of bladder cancer. Voided urine specimens were collected before procedure from these subjects (53 with confirmed tumor recurrence and 72 with confirmed non-tumor recurrence) for analysis. A prediction rule generated from the performance characteristics of 10 single biomarkers (IL8, MMP9, MMP10, SERPINA1, VEGFA, ANG, CA9, APOE, SERPINE1, and SDC1) was measured using ELISA. The diagnostic performance of the biomarker panel was assessed using receiver operator curves (ROC) and descriptive statistical values (e.g., sensitivity and specificity). Results: The combination of all 10 biomarkers outperformed any single biomarker with a calculated AUROC for the diagnostic panel of 0.904 [95% confidence interval (CI), 0.853–0.956]. The multiplex assay achieved an overall sensitivity of 79% and specificity of 88% for recurrent bladder cancer and significantly outperformed the Urovysion cytogenetic assay (sensitivity 42%, specificity 94%) and voided urinary cytology (sensitivity 33%, specificity 90%). Conclusions: A diagnostic panel of 10 urinary biomarkers that accurately detects primary bladder cancer also performs well for the detection of recurrent bladder cancer. Impact: The identification of a reliable urine-based surveillance and detection assay would be of benefit to both patients and the healthcare system. Cancer Epidemiol Biomarkers Prev; 23(7); 1340–5. ©2014 AACR.

Stroke remains an exceedingly incident and prevalent public health burden across the globe, with an estimated 16 million new strokes per annum and prevalence over 60 million, and extracranial internal carotid artery atherosclerotic disease is an important risk factor for stroke. Randomized trials of surgical treatment were conducted (North American Symptomatic Carotid Endarterectomy Trial, European Carotid Surgery Trial) and demonstrated efficacy of carotid endarterectomy for secondary prevention of stroke in patients with cerebrovascular events (e.g. ipsilateral stroke, transient ischemic attack, and/or amaurosis fugax) attributable to a diseased artery with 50–99% stenosis. Therapeutic clarity, however, proved elusive with asymptomatic carotid artery disease. Asymptomatic Carotid Atherosclerosis Study (ACAS), Asymptomatic Carotid Surgery Trial, and Veterans Affairs Cooperative Study (VACS) suggested only modest benefit from surgical intervention for primary stroke prevention and the best medical therapy at the time of these trials is not comparable to modern medical therapy. ACT-1, Asymptomatic Carotid Surgery Trial-2, Stent-Protected Angioplasty in asymptomatic Carotid artery stenosis versus Endarterectomy Trial-2, European Carotid Surgery Trial-2, Carotid Revascularization Endarterectomy Versus Stenting Trial-2 are trials that are recent, ongoing, or in development that include diverse populations across Europe and North America, complementary trial designs, and a collaborative spirit that should provide clinicians with evidence that informs best clinical practice for asymptomatic carotid artery disease.

Surveys are an important tool for assessing physician and nursing professionals’ practice patterns and guideline adherence. Obtaining quality survey data consisting of low item and unit nonresponse remains a persistent challenge in these populations. We tested the relative impact of two envelope types (padded vs. priority mail) on unit and item nonresponse in a survey of Minnesota health care workers. Respondents were randomized to receive a survey in one of two envelope types: a padded 8.5′′ × 11′′ envelope or a similarly sized priority mail envelope. After the first mailing, the response rate was 53.9% and did not differ across envelope conditions. Females and RNs were more likely to respond to the priority envelope than the padded envelope, but this finding did not hold in multivariate analysis. There was no difference in item nonresponse across the two envelope conditions. It may be that our two approaches were not enough to permeate the semi-porous membrane of gatekeeping that has been posited as a driver of low physician survey response rates relative to those observed in the general population. Nonetheless, our findings suggest that packaging may matter for some populations and not others.

Background Expansion of the endovascular and surgical workforce in the USA might lead to carotid revascularization procedures being carried out at low volume centers. Objective To evaluate trends in the treatment of carotid stenosis at high volume centers in the USA and compare outcomes by hospital volume. Methods Using the Nationwide Inpatient Sample, we evaluated trends in the proportion of carotid revascularization procedures performed at high volume centers in the USA from 2005 to 2011. High volume was defined as combined endarterectomy/stenting volume ≥130 patients/year, carotid endarterectomy volume ≥117 cases/year and carotid stenting volume ≥38 cases/year. In-hospital mortality, discharge to a long-term facility, intracranial hemorrhage, and postoperative stroke rates were compared between high and low volume centers. Results A total of 181 972 patients were included in this study. Overall, 63 442 patients (34.9%) were treated at high volume centers. The proportion of patients treated at high volume carotid revascularization centers decreased from 38.3% in 2005–2006 to 30.2% in 2010–2011. The proportion of patients treated at high volume centers decreased from 35.7% to 30.0% for carotid endarterectomy (p<0.0001) and 45.2% to 35.1% for carotid stenting. Patients treated at low volume centers had significantly higher rates of discharge to a long-term facility than high volume center patients (6.3% vs 5.0%, p<0.0001). The same was true for endarterectomy patients (6.0% vs 4.7%, p<0.0001) and stenting patients (8.3% vs 6.5%, p<0.0001). Conclusions A trend toward a lower proportion of patients with carotid stenosis being treated in high volume centers from 2005 to 2011 is concerning as these high volume centers had lower complication rates.

PurposeArchived formalin‐fixed paraffin‐embedded (FFPE) tissue collections represent a valuable informational resource for numerous studies. However, there is no NMR signal from FFPE specimens at room temperature. To obtain MR images and enable comparison of magnetic resonance microscopy (MRM) and histology studies we propose to image FFPE tissue at elevated temperature.MethodsA FFPE tissue block was imaged at 7 Tesla (T) and 16.4T at 70–80°C using T2‐weighting methods. The only difference from standard MR microscopy (MRM) is elevated temperature at which the embedding medium melts.ResultsUsing FFPE murine brain tissue, we were able to demonstrate the feasibility of tissue MRM from paraffin embedded specimens. Histology images taken from the specimen after MRM demonstrate that keeping the FFPE specimen in paraffin melt at 70–80°C for dozens of hours does not affect subsequent histology analysis.ConclusionMRM of FFPE tissue from paraffin melt opens new avenues for analyzing archived histological specimens (biopsies, post mortem, etc.) and for correlating MR images with histology (optical microscopy). In addition, 3D MRM of FFPE specimens could guide histology in search for appropriate regions of interest and subsequently minimize occurrences of false negatives in tissue analysis. Magn Reson Med 71:1989–1994, 2014. © 2014 Wiley Periodicals, Inc.

Abstract Purpose. The Oncotype DX colon cancer assay is a clinically validated predictor of recurrence risk in stage II colon cancer patients. This prospective study evaluated the impact of recurrence score (RS) results on physician recommendations regarding adjuvant chemotherapy in T3, mismatch repair-proficient (MMR-P) stage II colon cancer patients. Patients and Methods. Stage IIA colon cancer patients were enrolled in 17 centers. Patient tumor specimens were assessed by the RS test (quantitative reverse transcription-polymerase chain reaction) and mismatch repair (immunohistochemistry). For each patient, the physician's recommended postoperative treatment plan of observation, fluoropyrimidine monotherapy, or combination therapy with oxaliplatin was recorded before and after the RS and mismatch repair results were provided. Results. Of 221 enrolled patients, 141 patients had T3 MMR-P tumors and were eligible for the primary analysis. Treatment recommendations changed for 63 (45%; 95% confidence interval: 36%–53%) of these 141 T3 MMR-P patients, with intensity decreasing for 47 (33%) and increasing for 16 (11%). Recommendations for chemotherapy decreased from 73 patients (52%) to 42 (30%), following review of RS results by physician and patient. Increased treatment intensity was more often observed at higher RS values, and decreased intensity was observed at lower values (p = .011). Conclusion. Compared with traditional clinicopathological assessment, incorporation of the RS result into clinical decision making was associated with treatment recommendation changes for 45% of T3 MMR-P stage II colon cancer patients in this prospective multicenter study. Use of the RS assay may lead to overall reduction in adjuvant chemotherapy use in this subgroup of stage II colon cancer patients.