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Introduction and Objective: Guidelines from the American Urological Association (AUA) and American College of Radiology (ACR) recommend that patients with suspected nephrolithiasis undergo low-dose CT of the kidney, ureter, and bladder (LD CT KUB) as opposed to higher dose conventional imaging. We hypothesized that even at institutions with established LD protocols, higher dose imaging is common. Materials and Methods: We identified four academic medical centers where LD CT KUB protocols were implemented to yield an effective dose (EDose) consistent with national guidelines. Fifty consecutive adult patients who underwent CT KUB specifically for the evaluation of nephrolithiasis were retrospectively reviewed at each site. Patient age, sex, body mass index (BMI), imaging location, and EDose (millisieverts [mSv]) were recorded. Results: Two hundred patients with a mean age of 54 years were identified. Forty-six patients (23%) underwent CT KUB with an EDose ≤4 mSv, accounting for 10% to 48% of each institution's cohort. One hundred sixteen patients had a BMI

INTRODUCTION AND OBJECTIVE:Emergency Department (ED) discharge practices are subject to inter-provider variation that can limit the implementation of evidence-based medicine. We convened a multi-di...

Prostate specific antigen sensitivity increases with lower threshold values but with a corresponding decrease in specificity. Magnetic resonance imaging/ultrasound targeted biopsy detects prostate cancer more efficiently and of higher grade than standard 12-core transrectal ultrasound biopsy but the optimal population for its use is not well defined. We evaluated the performance of magnetic resonance imaging/ultrasound targeted biopsy vs 12-core biopsy across a prostate specific antigen continuum.We reviewed the records of all patients enrolled in a prospective trial who underwent 12-core transrectal ultrasound and magnetic resonance imaging/ultrasound targeted biopsies from August 2007 through February 2014. Patients were stratified by each of 4 prostate specific antigen cutoffs. The greatest Gleason score using either biopsy method was compared in and across groups as well as across the population prostate specific antigen range. Clinically significant prostate cancer was defined as Gleason 7 (4 + 3) or greater. Univariate and multivariate analyses were performed.A total of 1,003 targeted and 12-core transrectal ultrasound biopsies were performed, of which 564 diagnosed prostate cancer for a 56.2% detection rate. Targeted biopsy led to significantly more upgrading to clinically significant disease compared to 12-core biopsy. This trend increased more with increasing prostate specific antigen, specifically in patients with prostate specific antigen 4 to 10 and greater than 10 ng/ml. Prostate specific antigen 5.2 ng/ml or greater captured 90% of upgrading by targeted biopsy, corresponding to 64% of patients who underwent multiparametric magnetic resonance imaging and subsequent fusion biopsy. Conversely a greater proportion of clinically insignificant disease was detected by 12-core vs targeted biopsy overall. These differences persisted when controlling for potential confounders on multivariate analysis.Prostate cancer upgrading with targeted biopsy increases with an increasing prostate specific antigen cutoff. Above a prostate specific antigen threshold of 5.2 ng/ml most upgrading to clinically significant disease was achieved by targeted biopsy. In our population this corresponded to potentially sparing biopsy in 36% of patients who underwent multiparametric magnetic resonance imaging. Below this value 12-core biopsy detected more clinically insignificant cancer. Thus, the diagnostic usefulness of targeted biopsy is optimized in patients with prostate specific antigen 5.2 ng/ml or greater.

To correlate the highest percentage core involvement (HPCI) and corresponding tumor length (CTL) on systematic 12-core biopsy (SBx) and targeted magnetic resonance imaging/transrectal ultrasonography (MRI/TRUS) fusion biopsy (TBx), with total MRI prostate cancer (PCa) tumor volume (TV).Fifty patients meeting criteria for active surveillance (AS) based on outside SBx, who underwent 3.0T multiparametric prostate MRI (MP-MRI), followed by SBx and TBx during the same session at our institution were examined. PCa TVs were calculated using MP-MRI and then correlated using bivariate analysis with the HPCI and CTL for SBx and TBx.For TBx, HPCI and CTL showed a positive correlation (R(2)=0.31, P0.0001 and R(2)=0.37, P0.0001, respectively) with total MRI PCa TV, whereas for SBx, these parameters showed a poor correlation (R(2)=0.00006, P=0.96 and R(2)=0.0004, P=0.89, respectively). For detection of patients with clinically significant MRI derived tumor burden greater than 500 mm(3), SBx was 25% sensitive, 90.9% specific (falsely elevated because of missed tumors and extremely low sensitivity), and 54% accurate in comparison with TBx, which was 53.6% sensitive, 86.4% specific, and 68% accurate.HPCI and CTL on TBx positively correlates with total MRI PCa TV, whereas there was no correlation seen with SBx. TBx is superior to SBx for detecting tumor burden greater than 500 mm(3). When using biopsy positive MRI derived TVs, TBx better reflects overall disease burden, improving risk stratification among candidates for active surveillance.

Targeted magnetic resonance (MR)/ultrasound fusion prostate biopsy has been shown to detect prostate cancer. The implications of targeted biopsy alone vs standard extended-sextant biopsy or the 2 modalities combined are not well understood.To assess targeted vs standard biopsy and the 2 approaches combined for the diagnosis of intermediate- to high-risk prostate cancer.Prospective cohort study of 1003 men undergoing both targeted and standard biopsy concurrently from 2007 through 2014 at the National Cancer Institute in the United States. Patients were referred for elevated level of prostate-specific antigen (PSA) or abnormal digital rectal examination results, often with prior negative biopsy results. Risk categorization was compared among targeted and standard biopsy and, when available, whole-gland pathology after prostatectomy as the "gold standard."Patients underwent multiparametric prostate magnetic resonance imaging to identify regions of prostate cancer suspicion followed by targeted MR/ultrasound fusion biopsy and concurrent standard biopsy.The primary objective was to compare targeted and standard biopsy approaches for detection of high-risk prostate cancer (Gleason score ≥ 4 + 3); secondary end points focused on detection of low-risk prostate cancer (Gleason score 3 + 3 or low-volume 3 + 4) and the biopsy ability to predict whole-gland pathology at prostatectomy.Targeted MR/ultrasound fusion biopsy diagnosed 461 prostate cancer cases, and standard biopsy diagnosed 469 cases. There was exact agreement between targeted and standard biopsy in 690 men (69%) undergoing biopsy. Targeted biopsy diagnosed 30% more high-risk cancers vs standard biopsy (173 vs 122 cases, P .001) and 17% fewer low-risk cancers (213 vs 258 cases, P .001). When standard biopsy cores were combined with the targeted approach, an additional 103 cases (22%) of mostly low-risk prostate cancer were diagnosed (83% low risk, 12% intermediate risk, and 5% high risk). The predictive ability of targeted biopsy for differentiating low-risk from intermediate- and high-risk disease in 170 men with whole-gland pathology after prostatectomy was greater than that of standard biopsy or the 2 approaches combined (area under the curve, 0.73, 0.59, and 0.67, respectively; P .05 for all comparisons).Among men undergoing biopsy for suspected prostate cancer, targeted MR/ultrasound fusion biopsy, compared with standard extended-sextant ultrasound-guided biopsy, was associated with increased detection of high-risk prostate cancer and decreased detection of low-risk prostate cancer. Future studies will be needed to assess the ultimate clinical implications of targeted biopsy.clinicaltrials.gov Identifier: NCT00102544.

PURPOSE: Magnetic resonance imaging detects extracapsular extension by prostate cancer with excellent specificity but low sensitivity. This limits surgical planning, which could be modified to account for focal extracapsular extension with image directed guidance for wider excision. In this study we evaluate the performance of multiparametric magnetic resonance imaging in extracapsular extension detection and determine which preoperative variables predict extracapsular extension on final pathology when multiparametric magnetic resonance imaging predicts organ confined disease. MATERIALS AND METHODS: From May 2007 to March 2014, 169 patients underwent pre-biopsy multiparametric magnetic resonance imaging, magnetic resonance imaging/transrectal ultrasound fusion guided biopsy, extended sextant 12-core biopsy and radical prostatectomy at our institution. A subset of 116 men had multiparametric magnetic resonance imaging negative for extracapsular extension and were included in the final analysis. RESULTS: The 116 men with multiparametric magnetic resonance imaging negative for extracapsular extension had a median age of 61 years (IQR 57–66) and a median prostate specific antigen of 5.51 ng/ml (IQR 3.91–9.07). The prevalence of extracapsular extension was 23.1% in the overall population. Sensitivity, specificity, and positive and negative predictive values of multiparametric magnetic resonance imaging for extracapsular extension were 48.7%, 73.9%, 35.9% and 82.8%, respectively. On multivariate regression analysis only patient age (p=0.002) and magnetic resonance imaging/transrectal ultrasound fusion guided biopsy Gleason score (p=0.032) were independent predictors of extracapsular extension on final radical prostatectomy pathology. CONCLUSIONS: Because of the low sensitivity of multiparametric magnetic resonance imaging for extracapsular extension, further tools are necessary to stratify men at risk for occult extracapsular extension that would otherwise only become apparent on final pathology. Magnetic resonance imaging/transrectal ultrasound fusion guided biopsy Gleason score can help identify which men with prostate cancer have extracapsular extension that may not be detectable by imaging.

Objective To evaluate published evidence on nocturia in men and derive expert recommendations. Methods The International Consultations on Urological Diseases–Société Internationale d'Urologie convened a Consultation of experts on male lower urinary tract symptoms. The Consultation assigned standardized levels of evidence and grades of recommendation to various studies of nocturia epidemiology, pathophysiology, assessment, and treatment. Results Evidence review and consensus recommendations were made in the areas of epidemiology, pathophysiology, assessment, and treatment.Conclusion The review presents a condensed summary of the International Consultations on Urological Diseases–Société Internationale d'Urologie evaluation of nocturia, which offers contemporaneous expert consensus on this topic, with an assessment algorithm emphasizing the potential contribution of systemic conditions to the symptom.

Men diagnosed with atypical small acinar proliferation are counseled to undergo early rebiopsy because the risk of prostate cancer is high. However, random rebiopsies may not resample areas of concern. Magnetic resonance imaging/transrectal ultrasound fusion guided biopsy offers an opportunity to accurately target and later retarget specific areas in the prostate. We describe the ability of magnetic resonance imaging/transrectal ultrasound fusion guided prostate biopsy to detect prostate cancer in areas with an initial diagnosis of atypical small acinar proliferation.Multiparametric magnetic resonance imaging of the prostate and magnetic resonance imaging/transrectal ultrasound fusion guided biopsy were performed in 1,028 patients from March 2007 to February 2014. Of the men 20 met the stringent study inclusion criteria, which were no prostate cancer history, index biopsy showing at least 1 core of atypical small acinar proliferation with benign glands in all remaining cores and fusion targeted rebiopsy with at least 1 targeted core directly resampling an area of the prostate that previously contained atypical small acinar proliferation.At index biopsy median age of the 20 patients was 60 years (IQR 57-64) and median prostate specific antigen was 5.92 ng/ml (IQR 3.34-7.48). At fusion targeted rebiopsy at a median of 11.6 months 5 of 20 patients (25%, 95% CI 6.02-43.98) were diagnosed with primary Gleason grade 3, low volume prostate cancer. On fusion rebiopsy cores that directly retargeted areas of previous atypical small acinar proliferation detected the highest tumor burden.When magnetic resonance imaging/transrectal ultrasound fusion guided biopsy detects isolated atypical small acinar proliferation on index biopsy, early rebiopsy is unlikely to detect clinically significant prostate cancer. Cores that retarget areas of previous atypical small acinar proliferation are more effective than random rebiopsy cores.

To evaluate the correlation between multiparametric prostate MRI (MP-MRI) suspicion for seminal vesicle invasion (SVI) by prostate cancer (PCa) and pathology on MRI/ultrasound (US) fusion-guided biopsy.From March 2007 to June 2013, 822 patients underwent MP-MRI at 3 Tesla and MRI/US fusion-guided biopsy. Of these, 25 patients underwent targeted biopsy of the seminal vesicles (SVs). In six patients, bilateral SVI was suspected, resulting in 31 samples. MP-MRI findings that triggered these SV biopsies were scored as low, moderate, or high suspicion for SVI based on the degree of involvement on MRI. Correlative prostate biopsy and radical prostatectomy (RP) pathology were reviewed by a single genitourinary pathologist.At the time of MP-MRI, the median age was 64 years with a median prostate-specific antigen of 10.74 ng/mL. Of the 31 SV lesions identified, MP-MRI suspicion scores of low, moderate, and high were assigned to 3, 19, and 9 lesions, respectively. MRI/US fusion-guided biopsy detected SVI in 20/31 (65%) of cases. For the four patients who underwent RP after a preoperative assessment of SVI, biopsy pathology and RP pathology were concordant in all cases.As this technology becomes more available, MP-MRI and MRI/US fusion-guided biopsy may play a role in the preoperative staging for PCa. Future work will determine if improved preoperative staging leads to better surgical outcomes.

Background The ability to transfect and create transgenic cultured malaria parasites has transformed the study of Plasmodium falciparum over the last decade. With the completion of the annotated genome sequence, the process of gene discovery now routinely includes gene knockouts, over-expression and complementation analysis. However, while this technology has proven extremely valuable, significant limitations exist. In particular, P. falciparum DNA is often unstable and difficult to clone because of its AT-rich, repetitive nature. As a result, transgene expression constructs can be difficult to assemble due to the need to include two expression cassettes on a single plasmid, one to drive expression of the transgene of interest and a second for expression of the selectable marker. In addition, transgene expression levels are usually not regulatable, making it difficult to assess phenotypes that are sensitive to the amount of protein expressed. Results A plasmid based system for transgene expression is described that uses a single, bidirectional promoter to drive expression of both the transgene and the selectable marker, thus greatly reducing the size of the construct and enhancing stability. Further, by altering the concentration of drug used for selection, it is possible to modulate the copy number of the concatameric episomes and thereby regulate the expression level of the transgene through a range greater than 10 fold. Conclusion The transgene expression system described here should prove useful for both routine protein over-expression and complementation experiments as well as for experiments in which precisely manipulating the expression level of candidate proteins is desirable. This should provide an additional level of precision to the tools used to study the molecular biology of malaria parasites.

We evaluated the performance of multiparametric prostate magnetic resonance imaging (mp-MRI) and MRI/transrectal ultrasound (TRUS) fusion-guided biopsy (FB) for monitoring patients with prostate cancer on active surveillance (AS).Patients undergoing mp-MRI and FB of target lesions identified on mp-MRI between August 2007 and August 2014 were reviewed. Patients meeting AS criteria (Clinical stage T1c, Gleason grade ≤ 6, prostate-specific antigen density ≤ 0.15, tumor involving ≤ 2 cores, and ≤ 50% involvement of any single core) based on extended sextant 12-core TRUS biopsy (systematic biopsy [SB]) were included. They were followed with subsequent 12-core biopsy as well as mp-MRI and MRI/TRUS fusion biopsy at follow-up visits until Gleason score progression (Gleason ≥ 7 in either 12-core or MRI/TRUS fusion biopsy). We evaluated whether progression seen on mp-MRI (defined as an increase in suspicion level, largest lesion diameter, or number of lesions) was predictive of Gleason score progression.Of 152 patients meeting AS criteria on initial SB (mean age of 61.4 years and mean prostate-specific antigen level of 5.26 ng/ml), 34 (22.4%) had Gleason score ≥ 7 on confirmatory SB/FB. Of the 118 remaining patients, 58 chose AS and had at least 1 subsequent mp-MRI with SB/FB (median follow-up = 16.1 months). Gleason progression was subsequently documented in 17 (29%) of these men, in all cases to Gleason 3+4. The positive predictive value and negative predictive value of mp-MRI for Gleason progression was 53% (95% CI: 28%-77%) and 80% (95% CI: 65%-91%), respectively. The sensitivity and specificity of mp-MRI for increase in Gleason were also 53% and 80%, respectively. The number needed to biopsy to detect 1 Gleason progression was 8.74 for SB vs. 2.9 for FB.Stable findings on mp-MRI are associated with Gleason score stability. mp-MRI appears promising as a useful aid for reducing the number of biopsies in the management of patients on AS. A prospective evaluation of mp-MRI as a screen to reduce biopsies in the follow-up of men on AS appears warranted.