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OBJECTIVE To convene a multi-disciplinary panel to develop a pathway for Emergency Department (ED) patients with suspected nephrolithiasis and then prospectively evaluate its effect on patient care. MATERIALS AND METHODS The STONE Pathway was developed and linked to order sets within our Electronic Health Record in April 2019. Records were prospectively reviewed for ED patients who underwent ultrasound or Computerized Tomography (CT) to evaluate suspected nephrolithiasis between January 2019 and August 2019 within our institution. The primary outcome measure was the proportion of patients whose ED CT was low dose (

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

Objective To describe opioid prescribing patterns for patients undergoing kidney cancer surgery and evaluate associations with medical resource utilization in the postoperative setting. Methods Linked Surveillance, Epidemiology, and End Results - Medicare data were used to identify patients with kidney cancer who underwent partial or radical nephrectomy (open vs. minimally invasive) from 2007 to 2015. Total dose of discharge opioid prescriptions was quantified into 3 exposure groups based on observed tertiles: 1-199 (low), 200-300 (moderate), and >300 (high) oral morphine milligram equivalents. Associations between exposure groups and patient demographics, clinical factors, and hospital volumes were measured using multivariate logistic regression. Additionally, we identified associations with prior opioid exposure and postoperative medical resource utilization. Results Of 4538 patients meeting inclusion criteria, exposure group distributions were 35% (low), 43.5% (moderate) and 21.6% (high). Over one-third of patients (39.5%) received an opioid prescription within 6 months preceding surgery. High opioid prescriptions were associated with prior exposure, younger age, rural residence and open surgery (P Conclusion Prescribing patterns after kidney cancer surgery vary widely. Higher prescribed dose of post-surgical opioids is associated with 90-day hospital readmissions and long-term exposure. Prior opioid exposure conveys a higher risk of medical resource utilization. More judicious opioid prescribing may limit medical resource utilization and help combat the opioid epidemic.

Introduction:Concern regarding radiation exposure has led to increased interest in the use of ultrasound for the initial imaging of suspected renal colic in the emergency department. It is ...

Introduction:The overprescribing of opioids after urological surgery places patients at risk for opioid overuse and dependency. However, few guidelines exist to help urologists consistently...

Introduction:Postoperative kidney cancer surveillance is predominantly based on imaging and laboratory evaluation rather than physical exam. We sought to characterize the burden of kidney c...

The BCAN (Bladder Cancer Advocacy Network) Patient Survey Network identified pain during intravesical procedures as a research priority for patients. Although intraurethral lidocaine is the standard of care in this setting, evidence of its use is equivocal. We systematically reviewed studies of interventions to reduce discomfort during cystoscopy and intravesical therapy of bladder cancer. We performed a meta-analysis of interventions using available randomized, controlled trials.Search terms derived from the key questions were incorporated into the literature search constructed by a research librarian and the English medical literature from 1990 to 2017 was accessed. The initial search yielded 626 potential studies and the final review incorporated 62. We combined 12 trials into a meta-analysis with a random effects model of the efficacy of intraurethral lidocaine vs plain lubricant to reduce pain during flexible cystoscopy as measured on a 10-point visual analogue scale.Data from 12 randomized controlled trials in a total of 1,549 patients were included in the final intraurethral lidocaine meta-analysis. The standardized mean difference between visual analogue scale pain scores in patients who underwent flexible cystoscopy with intraurethral lidocaine and plain lubricant was -0.22 (95% CI -0.39--0.05). Evidence was insufficient to evaluate other interventions to mitigate the discomfort of invasive bladder procedures.Intraurethral lidocaine provides statistically significant pain reduction in men who undergo flexible cystoscopy, particularly with a longer dwell time. The evidence was insufficient for other tested interventions. A prospective study is needed to further clarify interventions to decrease patient discomfort during cystoscopy and other intravesical procedures in a diverse population.

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...

Surgical training has evolved considerably since the time of Halsted, with the “see one, do one, teach one” approach now replaced with graduated responsibility. Simulation has grown to play an increasingly important role in this process. The endourologic skill of ureteroscopy has been a particular focus of simulator development. Simulation platforms based on human cadavers, animal models, benchtop models, and virtual reality have all demonstrated high value and educational promise. This chapter reviews the concepts and terminology necessary to understand a simulator’s assessment, as well as the existing literature on simulation in ureteroscopy.

INTRODUCTION AND OBJECTIVE:American Urological Association (AUA) guidelines recommend low dose (

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.

We sought to determine whether computed tomography (CT) is an accurate tool for evaluation of reduction, prediction of neurologic deficit, and evaluation of need for revision surgery in unstable pelvic ring injuries treated with percutaneous sacroiliac (SI) screw fixation and whether any neural foramen penetration violation is safe. Using medical records and radiographic data, we retrospectively evaluated 46 patients with 51 fractures or widenings of the SI joint that were surgically treated with percutaneous SI screw fixation, either alone or associated with anterior fixation. Using the Young and Burgess classification, there were 3 vertical shear injuries, 13 lateral compression injuries, 17 anterior-posterior injuries, 7 sacral fractures, and 6 combination or unclassifiable pelvic injuries. Satisfactory reduction was obtained in all cases. All patients had postoperative CT scans, and 23 of 51 screws had some foramen penetration with an average of 3.3 mm (range, 1.4-7.0 mm). After percutaneous screw fixation, 10 of 46 patients had postoperative neurologic deficit, 4 of which were unchanged from preoperative evaluation. Of the 6 patients with new or worsened neurologic deficit, CT showed neural foramen penetration of 2.1 and 7.0 mm in 2 patients. Both patients underwent screw revision, resulting in improved neurologic deficit. The remaining 4 patients did not have foramen penetration; their neurologic function improved, with full return at 6 weeks without screw removal. Neural foramen penetration documented with CT did not correlate with neurologic deficit unless the penetration was greater than 2.7 mm. Postoperative CT showing neural foramen penetration was the cause of revision surgery in 2 of 10 patients with postoperative neurologic deficit after percutaneous SI screw fixation. Based on these findings, we recommend postoperative CT only in those cases where there is new neurologic deficit and screw removal if foramen penetration is greater than 2.1 mm. We also describe a new "safe zone" for screw insertion encompassing the superior 2 mm of the sacral foramen with adequate pelvic reduction.

Basal joint arthritis leads to thumb metacarpophalangeal (MCP) hyperextension that may prevent physiologic pinch. Various techniques have been used to address this hyperextension, but most are technically challenging, time-consuming, and not supported by long-term follow-up results. Furthermore, few groups have reported subjective, patient-based outcomes after such procedures. In a retrospective study, we evaluated a cohort of 14 patients who underwent a novel technique of thumb MCP capsulodesis in conjunction with basal joint arthroplasty. A mean of 4.74 years after surgery, subjective outcome measures (Disabilities of the Arm, Shoulder, and Hand questionnaire; visual analog scale for pain; patient satisfaction) and objective outcome measures (range of motion, grip and pinch strengths) all reflected excellent function. The described technique for MCP capsulodesis is an attractive adjunct to basal joint arthroplasty, but further prospective studies are needed to establish specific operative indications.

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.

Nocturia, or waking at night to void, is a common symptom that leads to substantial morbidity. Men and women are both affected across a wide age range, such that the objective evaluation of nocturia remains a challenge, due largely to its multifactorial etiology. While for some patients, nocturia is caused by common structural conditions such as prostatic obstruction, for others it is due to a complex interplay between multiple underlying systemic diseases. For this reason, persistent nocturia merits particularly careful consideration. The purpose of this review is to describe the most recent salient research in the field of nocturia, with a particular emphasis on its evaluation and management.

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.

INTRODUCTION AND OBJECTIVES: Tumor quantification with percent core and/or core length involvement is used to infer burden of disease for patients with prostate cancer (PCa). However, controversy exists regarding tumor quantification in random 12 core biopsies due to discrepancies in lesion targeting and overall needle core lengths obtained. Targeted magnetic resonance imaging/ultrasound (MRI/US) fusion biopsy allows for more optimal lesion targeting and interpretation of this parameter. We aim to correlate highest percentage core involvement and corresponding tumor length for both targeted fusion and random 12 core biopsies with total tumor volume. METHODS: Patients who underwent multiparametric MRI (MP MRI) with targeted MRI/US fusion biopsy at our institution between 2007 and 2013 were reviewed. MRI tumor volumes were calculated in fusion biopsy positive lesions and correlated with the highest percentage core involvement and corresponding tumor length in centimeters, for both targeted fusion biopsy and 12 core biopsy. Bivariate analysis was used to determine the empirical relationship between these variables and the correlative R2 value. RESULTS: 823 patients had MP MRI with MRI/US fusion biopsy, of which 100 patients had MRI tumor volumes quantified. Mean age was 62 years and mean PSA was 5.5ng/ml. For highest percentage core involvement, targeted biopsy showed a positive correlation (R1⁄40.54) whereas 12 core biopsy showed a poor correlation (R1⁄40.004) with total tumor volume (p

INTRODUCTION AND OBJECTIVES: Multiparametric 3T MRI (MP-MRI) with the use of an endorectal coil (ERC) provides improved signal to noise ratio for evaluation of prostatic lesions suspicious for prostate cancer. Herein, we aim to determine the degree of lesion identification lost by eliminating the use of an ERC based upon measures of obesity. METHODS: Prospectively collected data on 20 patients on an active surveillance protocol at the National Cancer Institute who have undergone non-ERC MP-MRI in 2013 following a prior ERC MP-MRI were analyzed. MP-MRI prostatic lesions suspicious for prostate cancer were identified and recorded on both ERC and non-ERC studies for each patient. Patient demographics including age, PSA, BMI, abdominal girth, waist circumference, and the drop distance from the anterior abdominal wall to the anterior aspect of the prostate were recorded. Quantitative measures of obesity were measured on T2-weighted MRI sequences. These parameters were analyzed using univariate and multivariable linear regression models individually with age and PSA to assess for significance in the decrease in number of lesions identified on followup studies without ERC use. RESULTS: The average number of lesions identified on ERC MP-MRI and followup non-ERC MP-MRI was 1.4 0.9 and 0.5 0.7, respectively. On univariate analysis, age and PSA were not significantly associated with a decrease in the number of lesions identified when the ERC was not used on followup MP-MRI. Of the quantitative parameters of obesity, on univariate analysis, greater BMI (p1⁄40.01) and abdominal girth (p1⁄40.0097) were significantly associated with a larger differential in the number of lesions identified. On multivariable linear regression models incorporating each of the measures of obesity with age and PSA, BMI (p1⁄40.026) and abdominal girth (p1⁄40.019) remained significant independent predictors of the difference in numbers of lesions identified between ERC and non-ERC studies. CONCLUSIONS: Typically more intraprostatic lesions are identified by MP-MRI performed with ERC due to the optimized signal to noise ratio. This difference is more dramatic in obese patients where the distance between body and surface coils and the prostate gland are increased. BMI and abdominal girth are predictors of significantly lower lesion identification when ERC is eliminated from the MP-MRI study. Since obesity has a negative impact on the detection of prostate cancer with non-ERC MRI, ERC use may be most important in this patient population.

INTRODUCTION AND OBJECTIVES: To overcome the wellknown prostate-specific antigen limits, several new biomarkers have been proposed. Since its introduction in clinical practice, the urinary prostate cancer gene 3 (PCA3) assay has shown promising results for prostate cancer (PC) detection. Furthermore, multiparametric magnetic resonance imaging (mMRI) has the ability to better describe several aspects of PC. METHODS: A prospective study of 171 patients with negative prostate biopsy findings and a persistent high prostate-specific antigen level was conducted to assess the role of mMRI and PCA3 in identifying PC. All patients underwent the PCA3 test and mMRI before a second transrectal ultrasoundguided prostate biopsy. The accuracy and reliability of PCA3 (3 different cutoff points) and mMRI were evaluated. Four multivariate logistic regression models were analyzed, in terms of discrimination and the cost benefit, to assess the clinical role of PCA3 and mMRI in predicting the biopsy outcome. A decision curve analysis was also plotted. RESULTS: Repeated transrectal ultrasound-guided biopsy identified 68 new cases (41.7%) of PC. The sensitivity and specificity of the PCA3 test and mMRI was 68% and 49% and 74% and 90%, respectively. Evaluating the regression models, the best discrimination (area under the curve 0.808) was obtained using the full model (base clinical model plus mMRI and PCA3). The decision curve analysis, to evaluate the cost/benefit ratio, showed good performance in predicting PC with the model that included mMRI and PCA3. CONCLUSIONS: mMRI increased the accuracy and sensitivity of the PCA3 test, and the use of the full model significantly improved the cost/benefit ratio, avoiding unnecessary biopsies. Source of Funding: none

INTRODUCTION AND OBJECTIVES: Active surveillance (AS) is a treatment strategy for prostate cancer (CaP) involving close monitoring of men diagnosed with low-risk CaP to reduce overtreatment. We report here factors associated with disease progression while on AS in a large, single institution cohort. METHODS: We retrospectively reviewed the data of men enrolled in the University of California at San Francisco (UCSF) AS cohort between 1990 and 2012. Strict eligibility criteria were prostatespecific antigen (PSA) 33% cores. Factors associated with progression while on active surveillance were determined through multivariate Cox proportional hazards regression. RESULTS: Of 1,106 men enrolled in AS at UCSF, 764 men have consented to participate in research to date and have been followed on AS for a median of 57 months. Of these, 520 (68%) met strict criteria for AS while 244 (32%) did not. The median number of repeat biopsies was 3 (IQR 2-4). At 5 years after diagnosis, 53 % were progression-free and 40% of patients received local therapy. Overall survival was 94% among those not AS eligible and 99% among those AS eligible at 5 years. There were no CaP-related deaths. In multivariate analysis, PSA density (PSAD), total number of biopsies, and later year of diagnosis were positively associated with the risk of both biopsy progression (HR (95% CI): 1.58 (1.33-1.88); 0.82 (0.72-0.94); 1.17 (1.11-1.25) , respectively) and receiving treatment (HR (95%CI): 1.39 (1.20-1.61); 0.71 (0.64-0.78); 1.20 (1.15-1.25), respectively), all p

INTRODUCTION AND OBJECTIVES: In patients with prostate cancer (CaP), preoperative identification of extracapsular extension (ECE) can provide vital information for the surgical planning of robotassisted radical prostatectomy (RARP). Historically, MRI has had limited sensitivity for ECE. We aim to evaluate which parameters on multiparametric MRI (MP-MRI) and MRI/ultrasound (MRI/US) fusionguided biopsy aid in the pre-operative assessment of ECE. METHODS: Between May 2007 and August 2013, 299 patients at our institution underwent 3T MP-MRI, MRI/US fusion-guided biopsy with standard 12-core biopsy, and RARP. Visualized lesions were identified as low, moderate, or high suspicion for CaP according to the previously validated NIH scoring system. Findings were characterized as “presence of ECE,” “extracapsular bulge,” or neither. MP-MRI findings were correlated with biopsy results, final RARP pathology and margin status. Univariate analysis was performed to evaluate preoperative predictors of ECE on final pathology. RESULTS: MRI was positive for ECE in 27 patients and negative in 272, with a sensitivity of 17.2% and a specificity of 93.2% when compared to final pathology. In all patients, the rate of positive surgical margins was 15.1%. This rate increased to 22.2% in the subset of patients with MRIs that were positive for ECE, but increased to 31.1% in those patients whose MRIs were false negatives. In the group of patients with negative MRIs, PSA, MRI suspicion score, presence of bulge, and highest Gleason score on MRI/US fusion-guided biopsy were all associated with ECE on final pathology (p

Purpose Proximal row carpectomy (PRC) is used as a treatment for a variety of wrist pathologies to maintain motion and to improve strength and decrease pain. Several studies have looked at how PRC alters wrist characteristics, although they did not provide an explanation for the variability observed in outcomes. Studies have classified the capitate into 3 unique types: round, V-shaped, or flat. We hypothesized that these differences in morphology could affect the contact biomechanics between the radius and the capitate after PRC. Methods A total of 14 cadaveric wrists underwent PRC. They were classified by capitate morphology and then loaded to 200 N in a neutral position, flexion, and extension. We measured contact area, contact pressure, and location using pressure-sensitive film in all 3 positions and compared their morphology types. Results Nine wrists had a round-type capitate, 4 had a V-shaped capitate, and 1 had a flat capitate, which we excluded from statistical analysis. Comparing round and V-shaped types, we found no differences in contact area, pressure, or location in any wrist position For the V-shaped capitates, there was increased contact pressure in flexion and extension compared with the wrist in neutral. Center of pressure translated dorsal and radial in flexion to volar and ulnar in extension for all types. Conclusions When we compared V-shaped and round-type capitates, we found no significant differences in contact characteristics of the wrist after PRC. There were some differences in contact pressure for V-shaped capitates in various wrist positions. Clinical relevance Differences between round and V-shaped capitates do not appear to affect contact biomechanics after PRC. Thus, these 2 capitate shapes may not necessarily be a factor in the decision-making process to perform PRC.

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.

57 Background: African-American (AA) men are at greater risk for prostate cancer (CaP) and experience increased prostate cancer-specific mortality. We aimed to determine racial disparities in CaP incidence, pathology, and anatomy identified on MRI/US fusion biopsy. Methods: Patients who underwent MP-MRI with targeted MRI/US fusion biopsy at our institution between May 2007 and June 2013 were reviewed. AA patients undergoing fusion biopsy were matched by age and PSA with a Caucasian cohort at a 1:2 ratio. MRI and pathologic parameters including lesion location, number of lesions, and Gleason score. Bivariate comparisons were made with the Student’s t-test and Χ2 analysis. Results: 822 patients had MRI/US fusion biopsy. 127 AA men were paired with a matched cohort of 254 Caucasians. Mean age was 60.2 and 61.4 years and mean PSA was 11.6 and 10.7ng/ml in AAs and Caucasians, respectively. We identified significantly more AA with CaP (49.6% vs 37.4%, p=0.03; Table). AAs also had higher grade disease (Gleason 7-10) versus white men (20.5% vs. 11.8%, p=0.04). Additionally, the diagnostic yield for the AA cohort was significantly higher per sampled lesion (37.5% vs 24.5%, p

63 Background: Active surveillance (AS) is an option for patients with low risk prostate cancer (PCa); however, determining disease progression is challenging. At the NCI, multiparametric MRI (MP-MRI) with our biopsy protocol (MR-US fusion-guided plus 12 core extended sextant biopsy) has been used to confirm eligibility for AS. We evaluated the utility of these modalities in monitoring patients on AS. Methods: Patients who underwent MP-MRI of the prostate with biopsy per our protocol between 2007-2012 were reviewed. We selected a subset who met Johns Hopkins criteria for AS (Gleason score≤6, PSA density≤0.15, tumor involvement of ≤2 cores, and ≤50% of any single core) by outside 12−core TRUS biopsy. Patients with Gleason score≤6 confirmed at first NCI biopsy session were followed with annual MP-MRI and biopsy. MRI progression was defined as an increase in MP-MRI suspicion level, lesion diameter, or number of lesions. Pathologic progression was defined as an increase to Gleason score≥7 in either 12-core or MR-fusion biopsy. We determined the association between MRI and pathologic progression. Results: 129 patients met JHU criteria for AS by outside biopsy. Mean age was 61.6 years and mean PSA 5.16ng/mL. 28/129 (21.7%) patients had Gleason score ≥7 at first NCI biopsy session.31 patients had at least two biopsy sessions (mean follow up 18 months, range 12-54 months) of which 9/31 (29%) increased in Gleason score, all to 3+4=7. Fusion biopsy detected more pathologic progression than did standard biopsy (Table). The positive predictive value of MP-MRI for pathologic progression was 50%, while the negative predictive value was 84%. The sensitivity and specificity of MP-MRI for increase in Gleason score was 67% and 73%, respectively. Conclusions: Stable findings on MP-MRI are associated with Gleason score stability in patients with low-risk PCa choosing AS. The majority of patients who had pathologic progression were detected on fusion biopsy, which may suggest that random biopsies are unnecessary in this population. Larger studies are needed to validate these findings. [Table: see text]

84 Background: Historically, pathologic findings from standard 12-core prostate biopsies are upgraded in 25 to 33% of patients after radical prostatectomy (RP). MRI/US fusion prostate biopsy has been shown to upgrade prostate cancer compared to standard 12-core biopsy in 32% of patients. MRI/US fusion biopsy may offer a more accurate representation of whole gland pathology. We evaluate the rate of pathologic upgrade in standard 12-core biopsy and MRI/US fusion biopsy when compared with whole gland pathology from RP. Methods: Patients who underwent random prostate biopsy, fusion biopsy and subsequently RP for prostate cancer from 2012 to 2013 were included. Pathology was reviewed by a single pathologist. The cohort was divided into clinically significant high-grade (Gleason score 4+3 or higher) and clinically insignificant low-grade (Gleason score 3+4 or lower) sub cohorts. Pathological upgrade was defined as any increase in Gleason sum or primary Gleason score. McNemar’s test was used to compare the proportion of patients who were upgraded from random biopsy to RP versus the proportion that were upgraded from fusion biopsy to RP. Results: Sixty eight patients underwent 12-core and fusion prostate biopsy then subsequently RP. Mean prostate-specific antigen was 9.2ng/ml. There are total of 43 patients with clinically insignificant low-grade and 25 patients with clinically significant high-grade. Fusion biopsy upgraded 19 patients (28%) compared to 12-core biopsy, eight of these patients had negative 12-core biopsy. Pathology on the RP specimen upgraded 18 of the 12-core results (26%) compare to only eight fusion biopsy results (11%). (p =0.0095) 14 patients (20%) who had clinically insignificant low-grade disease on 12-core biopsy were upgraded to clinically significant high-grade on RP. Only two patients (3%) with clinically insignificant low-grade from fusion biopsy were upgraded on RP. (p< 0.0005) Conclusions: Prostate cancer detected on MRI/US fusion prostate biopsy has significantly lower rates of pathologic upgrade than standard 12-core biopsy when both were compared to prostatectomy specimens. MRI/US fusion biopsy may represent whole gland pathology more accurately compared to 12-core biopsy.