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Injuries to the bladder are infrequent and commonly result from blunt, penetrating, or iatrogenic trauma. Bladder injuries may be missed as they often present concomitantly with other abdominal and pelvic injuries; however, early detection and treatment are essential as morbidity and mortality may be significant. Gross hematuria, especially in the setting of pelvic fractures, may be indicative of a bladder injury which can be confirmed with cystography. Extraperitoneal injuries are commonly managed conservatively with catheter drainage while intraperitoneal ruptures traditionally required surgical exploration and closure. Presented is a contemporary review which encapsulates the etiology, presentation, assessment, and management of bladder injuries.

PURPOSE: Low temperature sensitive liposome (LTSL) encapsulated docetaxel were combined with mild hyperthermia (40–42°C) to investigate in vivo biodistribution and efficacy against a castrate resistant prostate cancer. METHOD: Female athymic nude mice with human prostate PC-3 M-luciferase cells grown subcutaneously into the right hind leg were randomized into six groups: saline (+/− heat), free docetaxel (+/− heat), and LTSL docetaxel (+/− heat). Treatment (15 mg docetaxel/kg) was administered via tail vein once tumors reached a size of 200–300 mm(3). Mice tumor volumes and body weights were recorded for up to 60 days. Docetaxel concentrations of harvested tumor and organ/tissue homogenates were determined by LC-MS. Histological evaluation (Mean vessel density, Ki67 proliferation, Caspase-3 apoptosis) of saline, free Docetaxel and LTSL docetaxel (+/− heat n = 3–5) was performed to determine molecular mechanism responsible for tumor cell killing. RESULT: LTSL/heat resulted in significantly higher tumor docetaxel concentrations (4.7-fold greater compared to free docetaxel). Adding heat to LTSL Docetaxel or free docetaxel treatment resulted in significantly greater survival and growth delay compared to other treatments (p < 0.05). Differences in body weight between all Docetaxel treatments were not reduced by >10% and were not statistically different from each other. Molecular markers such as caspase-3 were upregulated, and Ki67 expression was significantly decreased in the chemo-hyperthermia group. Vessel density was similar post treatment, but the heated group had reduced vessel area, suggesting thermal enhancement in efficacy by reduction in functional perfusion. CONCLUSION: This technique of hyperthermia sensitization and enhanced docetaxel delivery has potential for clinical translation for prostate cancer treatment.

Objective To compare the frequency and severity of erectile dysfunction (ED) among pelvic fracture patients with and without urethral injuries and to identify potential risk factors for ED in the setting of pelvic fracture injury. Materials and Methods A retrospective review was conducted of male patients treated for pelvic fractures with and without urethral injuries at a Level 1 trauma center between 2005 and 2016. The International Index of Erectile Function (IIEF-5) questionnaire was administered to patients by telephone to assess post-injury ED. Additional questions about pre-injury ED, post-injury symptoms, and past medical history were reviewed. Results Fifty patients (42%, n = 118) responded to the IIEF-5 questionnaire: 29 with pelvic fractures alone and 21 with PFUIs. We observed a numerical increase in frequency of new onset ED in patients with pelvic fracture urethral injuries (PFUIs) (n = 12, 57%) compared with patients with pelvic fractures alone (n = 11, 38%) (P = .3). Patients with PFUIs reported lower IIEF-5 scores (ie worse ED) than patients with pelvic fractures alone (13 versus 18, P = .05). There were no significant differences in potential risk factors between the 2 groups on univariate analyses. Conclusion ED was more severe following PFUI than pelvic fracture alone. We suspect that urethral injury is not the direct cause of ED, but rather a surrogate for extensive pelvic injury and risk for neurovascular injury. A larger prospective analysis is warranted to clarify this hypothesis and to further stratify risk factors for developing ED in pelvic fracture patients with and without urethral injuries.

Objective: Many patients who undergo inflatable penile prosthesis (IPP) replacement are often upsized to larger cylinders, suggesting the IPP may serve as a tissue expander and increase internal penile length. The objective of this study is to evaluate whether cylinder length increases with subsequent IPP insertion. Materials and Methods: We queried American Medical Systems and Coloplast Patient Information Form databases to identify patients who underwent IPP placement and replacement between 2004-2013. Patients were grouped by device type and time to replacement (0.5 cm and 40% demonstrated increases of ≥1 cm. Conclusions: As demonstrated, the IPP may provide tissue expansion over time. Further evaluation is needed to determine if increased cylinder length correlates to increased functional length and patient satisfaction.

Purpose: To report our initial results of robotic appendicovesicostomy (APV) revision in children. Patients and Methods: Three patients (median age 6 years; range 6–13) underwent robot-assisted APV surgery for bladder dysfunction because of posterior urethral valves, myelomeningocele, and traumatic spinal cord transection. Leakage developed in each patient from the APV. After failing more conservative treatments, the patients subsequently underwent robot-assisted APV revision. Results: Robot-assisted APV revision was conducted at a median 14 months (range 6–34 mos) after initial surgery. Median operative time was 165 minutes (range 106–232 min), and blood loss was ≤5 mL for all patients. Intraoperative findings ranged from partial to complete separation of the APV from the bladder tunnel. APV leakage resolved for all patients at last follow-up (median 5 months; range 2–9 mos). Conclusion: This initial series expands the scope of robotic surgical procedures in children. Robot-assisted APV revision...

Objective To report surgical and functional outcomes of buried penis surgery. Methods Outcomes following buried penis surgery at the University of Washington were assessed from June 1, 2005 to June 1, 2016. Patient demographic and surgical data were abstracted from a retrospective chart review. All patients were attempted to be contacted by phone for long-term follow-up. Uni- and multivariate analysis was performed to evaluate for association with any complication. Results A total of 42 men underwent buried penis repair surgery (mean short-term follow-up 8.1 months). There was an overall 33% 90-day complication rate (21 events). In univariate analysis, body mass index (BMI; P = .02) and no history of gastric bypass ( P = .03) were significant predictors of any complication. In multivariate analysis, only BMI remained significant (odds ratio 1.1 for each increase in unit of BMI, 95% confidence interval 1.01-1.27). Twenty-seven patients were reached for long-term follow-up (mean 39 months). Patients reported improvements in every functional domain that was assessed. Of the patients, 85% reported they would undergo buried penis surgery again, 74% that surgery led to a positive change in their lives, and 85% that the surgery had remained a long-term success. Conclusion Surgical correction of buried penis with penile split-thickness skin graft and limited panniculectomy is well tolerated and results in functional, long-term improvements. BMI is associated with an increased likelihood of a complication following surgery.

Lower urinary tract foreign bodies have been reported in both children and adults. It is helpful for urologists to review foreign body case reports to become familiar with alternative approaches for removal that may prove helpful during challenging cases. To our knowledge, we describe for the first time a degraded rare-earth magnet within the body and use of Hartmann ear forceps to remove a foreign body from the urethra under cystoscopic guidance through a limited urethrotomy.

A novel platform was developed that fuses pre-biopsy magnetic resonance imaging with real-time transrectal ultrasound imaging to identify and biopsy lesions suspicious for prostate cancer. The cancer detection rates for the first 101 patients are reported.This prospective, single institution study was approved by the institutional review board. Patients underwent 3.0 T multiparametric magnetic resonance imaging with endorectal coil, which included T2-weighted, spectroscopic, dynamic contrast enhanced and diffusion weighted magnetic resonance imaging sequences. Lesions suspicious for cancer were graded according to the number of sequences suspicious for cancer as low (2 or less), moderate (3) and high (4) suspicion. Patients underwent standard 12-core transrectal ultrasound biopsy and magnetic resonance imaging/ultrasound fusion guided biopsy with electromagnetic tracking of magnetic resonance imaging lesions. Chi-square and within cluster resampling analyses were used to correlate suspicion on magnetic resonance imaging and the incidence of cancer detected on biopsy.Mean patient age was 63 years old. Median prostate specific antigen at biopsy was 5.8 ng/ml and 90.1% of patients had a negative digital rectal examination. Of patients with low, moderate and high suspicion on magnetic resonance imaging 27.9%, 66.7% and 89.5% were diagnosed with cancer, respectively (p0.0001). Magnetic resonance imaging/ultrasound fusion guided biopsy detected more cancer per core than standard 12-core transrectal ultrasound biopsy for all levels of suspicion on magnetic resonance imaging.Prostate cancer localized on magnetic resonance imaging may be targeted using this novel magnetic resonance imaging/ultrasound fusion guided biopsy platform. Further research is needed to determine the role of this platform in cancer detection, active surveillance and focal therapy, and to determine which patients may benefit.

We determined whether there is a correlation between D'Amico risk stratification and the degree of suspicion of prostate cancer on multiparametric magnetic resonance imaging based on targeted biopsies done with our electromagnetically tracked magnetic resonance imaging/ultrasound fusion platform.A total of 101 patients underwent 3 Tesla multiparametric magnetic resonance imaging of the prostate, consisting of T2, dynamic contrast enhanced, diffusion weighted and spectroscopy images in cases suspicious for or with a diagnosis of prostate cancer. All prostate magnetic resonance imaging lesions were then identified and graded by the number of positive modalities, including low-2 or fewer, moderate-3 and high-4 showing suspicion on multiparametric magnetic resonance imaging. The biopsy protocol included standard 12-core biopsy, followed by real-time magnetic resonance imaging/ultrasound fusion targeted biopsies of the suspicious magnetic resonance lesions. Cases and lesions were stratified by the D'Amico risk stratification.In this screening population 90.1% of men had a negative digital rectal examination. Mean±SD age was 62.7±8.3 years and median prostate specific antigen was 5.8 ng/ml. Of the cases 54.5% were positive for cancer on protocol biopsy. Chi-square analysis revealed a statistically significant correlation between magnetic resonance suspicion and D'Amico risk stratification (p0.0001). Within cluster resampling demonstrated a statistically significant correlation between magnetic resonance suspicion and D'Amico risk stratification for magnetic resonance targeted core biopsies and magnetic resonance lesions (p0.01)Our data support the notion that using multiparametric magnetic resonance prostate imaging one may assess the degree of risk associated with magnetic resonance visible lesions in the prostate.

To present a novel algorithm for definitive reconstruction of penile curvature in men undergoing inflatable penile prosthesis (IPP) surgery as an alternative to manual penile modeling and grafting procedures.Patients with erectile dysfunction and concomitant penile curvature undergoing IPP placement were divided into 2 treatment groups: (1) group 1, penile deformity known preoperatively, and (2) group 2, penile curvature recognized intraoperatively after IPP placement. Group 1 patients underwent penile plication after artificial erection and immediately before IPP insertion via the same penoscrotal incision, whereas group 2 patients were treated with a Yachia (Heineke-Mikulicz) corporoplasty over the intact cylinders. Patients completed postoperative Patient Global Impression of Improvement (PGI-I) questionnaires assessing overall satisfaction.Among 405 men receiving IPP at our institution from 2007 to 2014, 30 patients received synchronous correction of penile curvature (7%). Group 1 included 23 of 30 (77%) patients, and 7 of 30 (23%) were in group 2. Overall mean initial curvature was 36°, and all patients were corrected to10°. Average operative times were 18 minutes longer compared with patients who underwent IPP placement alone (82 vs 64 minutes, P.05). At an average follow-up of 13 months (range 7-32), 19 of 20 (95%) group 1 and 6 of 7 (86%) group 2 patients who completed surveys reported an improved overall condition. No patient reported chronic pain, recurrent deformity, or device malfunction.Penile curvature can be safely and reliably corrected at the time of IPP placement, regardless of whether the deformity was identified preoperatively.

We evaluated the risk of histologic upgrading and upstaging in patients who met strict active surveillance (AS) criteria on saturation biopsy and elected to undergo radical prostatectomy.A retrospective review was conducted of 362 consecutive, individual patients who underwent transrectal ultrasound guided saturation biopsy (32 cores) between 2006 and 2013. Thirty-one patients (9%) were eligible for AS based on Hopkins criteria for very low risk (VLR): stage T1c, prostate-specific antigen (PSA) density ≤ 0.15 ng/mL2, Gleason ≤ 6, ≤ 2 cores and ≤ 50% core. Twenty patients (64%) elected radical prostatectomy, 2 (7%) elected radiation treatment and 9 (29%) elected AS (n = 9, 29%). Radical prostatectomy results were used to evaluate for upgrading and upstaging.Patient and saturation biopsy characteristics were similar amongst radical prostatectomy, radiation and AS patients. Mean age was 63 years (range 50-75) and 27 patients (87%) had a prior negative biopsy. Median time to prostatectomy was 3 months (range 1-46). Upgrading (Gleason ≥ 7) was identified in 40% (n = 8) of patients: Gleason 3+4 (n = 7) and Gleason 4+3 (n = 1). Upstaging (≥ T3) was not identified. Mean follow up was 47 months (range 11-99) for all patients. No patient developed biochemical recurrence or required salvage treatment.Despite increased prostate sampling, patients who met strict AS criteria on saturation biopsy were at high risk for Gleason upgrading, but fortunately at low risk for upstaging and biochemical recurrence. Patients contemplating AS based on saturation biopsy results should be counseled appropriately. MRI-TRUS fusion biopsy may be an alternative to saturation biopsy until proven otherwise.

This paper uses phospholipase Cepsilon as a model to demonstrate that lipids can act as ligands to bind to specific motifs and regulate protein activity via allosteric effects. Phospholipids such as phosphatidic acid and free fatty acids such as arachidonate are potent activators of PLCepsilon, increasing the rate of PI hydrolysis by 8-fold and 50-fold, respectively. The mechanism appears to be a reduction of K(m), as the substrate dependence curve is shifted to the left and K(m) is reduced 10-fold. The regulation of PLCepsilon by lipids appears to be physiologic, as reconstitution or cotransfection of either cPLA(2) or PLD with PLCepsilon leads to activation of phosphodiesterase activity. Additionally, TSA-201 cells transfected with PLCepsilon and fed arachidonic acid complexed with BSA had increased (4-5-fold) hydrolysis of polyphosphoinositides. This study demonstrates the ability of lipids to act as potent and direct mediators of protein function and identifies cross talk between different classes of phospholipase (PLD and PLA(2) with PLC) mediated via lipid products.

Objective To present our updated experience and patient-reported outcomes of high submuscular (HSM) placement of urologic prosthetic balloons and reservoirs (UPBRs). Methods A retrospective review was performed of patients who underwent inflatable penile prosthesis and/or artificial urinary sphincter placement between 2011 and 2013. UPBRs were placed in an HSM location between the transversalis fascia and the rectus abdominis muscle by blunt dissection through the external inguinal ring via a trans-scrotal approach. Patient demographics, perioperative outcomes, and patient-reported outcomes were reviewed. Results During the study period, 146 patients received 158 HSM implants: inflatable penile prosthesis reservoirs (n = 93) or artificial urinary sphincter balloons (n = 65). Patients completed a standardized survey at a mean of 3.2 months (range, 1.1-23.4 months) after surgery and were last followed up at a mean of 5.5 months (range, 1.1-28.7 months). Overall, 94% (n = 149) of UPBRs caused no bother, and patients were satisfied with 96% (n = 151) of implants. Patients were unable to palpate 80% (n = 126) of UPBRs and minimally palpate 16% (n = 26). The primary surgeon was unable to palpate 72% (n = 115) of UPBRs and minimally palpate 20% (n = 31). Type of UPBR, body mass index, reservoir volume, and reservoir manufacturer were not associated with patient or surgeon palpability. Of the 158 UPBRs placed, only 2 (1.3%) were revised due to bothersome patient palpability. No bowel, bladder, ureteral, or vascular injuries occurred. Conclusion HSM placement of UPBR is safe and feasible, well tolerated, and avoids deep retropubic dissection. Patient-reported outcomes support low palpability, low bother, and high patient satisfaction.

Prostate cancer continues to be the second leading cause of cancer related mortality in men within the United States. Despite a consistent decline in prostate cancer mortality over the past two decades, the prognosis for men with metastatic prostate cancer remains poor with no curative therapies. In this article, we review the recently approved and emerging therapeutics for patients with castrate resistant prostate cancer.An advanced search was conducted on the clinicaltrials.gov database, using search terms "metastatic prostate cancer", and limiting results to phase II-IV clinical trials. Clinically relevant emerging therapeutics were selected and a Medline search for supporting documents was performed. An emphasis was placed on newly approved and promising new therapeutics.A total of four Food and Drug Administration approved medications and eight investigational agents were chosen for review. The background and role of these therapeutics in the treatment of prostate cancer treatment is discussed.The past few years have yielded a near exponential increase in treatments for metastatic prostate cancer, many of which have a unique mechanism of action. The estimated median survival for patients with metastatic prostate cancer remains dynamic as we begin to integrate these therapeutics into clinical practice and determine the optimal sequence and timing of treatment.

Objective To compare the safety and efficacy of patients undergoing dorsal penile plication with patients undergoing ventral and lateral plication. Methods A retrospective review was performed of all patients who underwent penile plication between 2007 and 2013. Plication was performed through a 2-cm longitudinal incision in the proximal or midpenile shaft without degloving. Plication sutures were placed in parallel opposite the angle of greatest curvature. Dorsal plication was performed with minimal displacement of the neurovascular bundle. Patient demographics, perioperative outcomes, and patient-reported outcomes were analyzed. Results Of 215 patients who underwent penile plication, complete operative and patient-reported outcomes data were available for 118 (55%). Patients were grouped by location of plication: dorsal (n = 17 [14%]), ventral (n = 65 [55%]), and lateral (n = 36 [31%]). Mean age (52-58 years; P = .51) and preoperative curvature (36-51°; P = .78) were similar among the 3 groups. Each group required a similar number of sutures (8-9; P = .18) to achieve similar correction (37-45°; P = .33). Patients completed a satisfaction survey at a mean of 15 months (range, 1-41 months) after surgery. All groups reported equally high rates of satisfaction for penile curvature ( P = .64), penile rigidity ( P = .64), strength of erection ( P = .98), and overall satisfaction ( P = .75). Although each group reported subjective decrease in penile length ( P = .10), objective length loss occurred on a small scale (mean length loss for all groups, 0.3-0.8 cm; P = .24). Conclusion Penile plication is a safe and effective technique for correcting all directions of curvature. Dorsal plication without degloving produces favorable objective and subjective results comparable to ventral and lateral plication.

Twenty to thirty percent of patients with Peyronie's disease (PD) have erectile dysfunction (ED) refractory to medical therapy and may benefit from a combined procedure addressing both conditions.The aim of this study was to show the efficacy of inflatable penile prosthesis (IPP) insertion and synchronous penile plication for correcting penile curvature and ED in patients with PD.A retrospective review was performed of all patients who underwent IPP insertion with synchronous penile plication at our tertiary care center between 2010 and 2013. All patients received an intraoperative saline intracorporal injection to induce an artificial erection. After the tunica albuginea was exposed via a standard transverse scrotal incision over the proximal penile shaft, the incision was retracted distally and/or laterally as needed for plication suture placement. Plication sutures were placed in parallel opposite the angle of greatest curvature. The incision was returned proximally to the standard penoscrotal junction for IPP insertion. Demographic and surgical data were collected from the patients' medical records. Patient satisfaction was assessed postoperatively using a nonvalidated questionnaire.The focus of this study was surgical outcomes, both technical and patient-reported satisfaction.Eighteen patients with a mean age of 63 years underwent IPP insertion with synchronous penile plication. Patients presented with dorsal (n = 11), lateral (n = 2), and biplanar curvature (n = 5). Mean preoperative curvature was 39 degrees (range 30-60) and was corrected on average to5 degrees (range5-12) using a median of four plication sutures (range 3-6). Among 15 patients completing a postoperative satisfaction survey at a mean of 11 months, all reported improvement in their overall condition and penile curvature; one with biplanar deformity reported minor residual curvature. None reported continued pain or required suture release.IPP insertion with synchronous penile plication for the correction of ED and PD is effective and results in high patient satisfaction.

10.8 mos (range: 0.7-37.8). The median primary renal mass size was 8.3cm with 5.9cm sized necrosis. Among the three different times of CT scans, higher correlation of first CT with prognosis of progression (OR 5.843, p1⁄40.022) was found than the others. The tumor size reduction with necrotic size increasing (0.72cm, HR 2.505, CI 1.348-4.655; p1⁄40.004) at initial CT after 1st or 2nd cycle of TT, enhancing HU changes after TTS compared to baseline CT (HR 0.967, CI 0.938-0.996; p1⁄40.025), and RCC histology (HR 0.004 CI 0.000-0.597, p1⁄40.031) were significantly related to the prognosis of survival in patients with mRCC in multivariate analysis (p

INTRODUCTION AND OBJECTIVES: The true reoperation rate of penile prosthetic surgery is unknown due limited data from retrospective, single institution studies. This study aims to evaluate the reoperation rate after virgin penile prosthetic surgery using a large population database METHODS: A longitudinal analysis of California Office of Statewide Health Planning and Development database from 1995 to 2010 was performed. Inclusion criteria were men who underwent their first penile prosthetic surgery. Patients were excluded if they had an explant of a prior prosthesis at the time of their first recorded surgery. Primary outcome was reoperation, specified as the removal or replacement of the prosthesis. Censoring events included penile amputation, surgeries of the genitalia or pelvis, and cancer involving the genitourinary organs. Statistical analysis was performed via KaplanMeier plot, hazard curve, and multivariate analysis adjusting for age, race, gender, comorbidities, insurance status, hospital volume and teaching status RESULTS: 7,666 patients (40,932 patient years) were included in the study. The 5 and 10-year cumulative reoperation rates were 11.2% (CI: 10.5-12.0%) and 15.7% (CI: 14.7-16.8%) respectively. Malfunction and infection accounted for 57% and 27% of reoperations. Reoperation rate was highest at 1 year post-operatively (3.4% per year), and steadily declined until 2 years post-operatively, after which it remained at roughly 1.25% per year. Multivariate analysis showed higher rates of reoperation among younger patients (HR1⁄41.51, CI: 1.122.05 for 75yo), African American patients (HR1⁄41.30, CI: 1.05-1.62), and Hispanic patients (HR1⁄41.32, CI: 1.121.57). 22.9% of the reoperations were performed at a hospital different from the initial implantation CONCLUSIONS: Reoperation rate for penile prosthetic surgery is highest in the first year postoperatively. The patients with highest risk for reoperation are African American, Hispanics, and younger age for unclear reasons that warrant further study. Nearly a quarter of reoperations occur at a hospital different from the initial surgery, suggesting that existing literature does not reflect the true prevalence of penile prosthetic complications

Androgen deprivation therapy is the mainstay treatment for patients with prostate cancer who are not candidates for definitive treatment, are diagnosed with advanced disease on initial presentation or progress after primary treatment. Patients who stop responding to androgen deprivation therapy develop castration resistant prostate cancer (CRPC). Emerging drugs undergoing clinical evaluation and drugs that have recently received FDA approval for the treatment of CRPC are reviewed.As the natural history and signaling pathways of prostate cancer are better understood, new treatments and targeted therapies will be developed. The FDA recently approved 5 medications that increase survival in patients with CRPC. Additional medications and drug classes are being explored that may eventually lead to new treatment options. Articles were identified using a PubMed database search.Recent FDA medication approvals and the development of emerging treatments are promising for the future of patients with prostate cancer. The addition of new medications challenges physicians to identify the optimal sequence and/or combination in which newer and older medications should be administered. Physicians treating patients with prostate cancer have a growing responsibility to keep pace with these new medications so that they may counsel and treat patients appropriately.

Objectives Minimally invasive robotic assistance is being increasingly utilized to treat larger complex renal masses. We report on the technical feasibility and renal functional and oncologic outcomes with minimum 1 year follow-up of robot-assisted laparoscopic partial nephrectomy (RALPN) for tumors greater than 4 cm. Materials and methods The urologic oncology database was queried to identify patients treated with RALPN for tumors greater than 4 cm and a minimum follow-up of 12 months. We identified 19 RALPN on 17 patients treated between June 2007 and July 2009. Two patients underwent staged bilateral RALPN. Demographic, operative, and pathologic data were collected. Renal function was assessed by serum creatinine levels, estimated glomerular filtration rate, and nuclear renal scans assessed at baseline, 3, and 12 months postoperatively. All tumors were assigned R.E.N.A.L. nephrometry scores ( http://www.nephrometry.com ). Results The median nephrometry score for the largest tumor from each kidney was 9 (range 6–11) while the median size was 5 cm (range 4.1–15). Three of 19 cases (16%) required intraoperative conversion to open partial nephrectomy. No renal units were lost. There were no statistically significant differences between preoperative and postoperative creatinine and eGFR. A statistically significant decline of ipsilateral renal scan function (49% vs. 46.5%, P = 0.006) was observed at 3 months and at 12 mo postoperatively (49% vs. 45.5%, P = 0.014). None of the patients had evidence of recurrence or metastatic disease at a median follow-up of 22 months (range 12–36). Conclusions RALPN is feasible for renal tumors greater than 4 cm with moderate or high nephrometry scores. Although there was a modest decline in renal function of the operated unit, RALPN may afford the ability resect challenging tumors requiring complex renal reconstruction. The renal functional and oncologic outcomes are promising at a median follow-up of 22 months, but longer follow-up is required.

We evaluate presentation and outcome of patients with metastatic RCC to the gallbladder from our institution and published literature.Patients with a history of gallbladder metastasis from RCC were selected from our institution's prospective database. A systematic PubMed search was performed to identify articles describing patients with metastatic RCC to the gallbladder. The final cohort included 33 patients: 4 from our institution and 29 from 28 previously published cases. Survival analysis was conducted using log-rank Kaplan-Meier analysis.Median patient age was 63 years and the majority of patients were male. Most patients were asymptomatic and diagnosed with gallbladder metastasis on imaging performed for surveillance or staging. The median time to gallbladder metastasis following nephrectomy was 4 years. Metastasis to the gallbladder occurred both synchronously (33%) and metachronously (67%). Of the patients with available histology, all had clear cell RCC (n = 28). Of all patients, 13 (39%) had metastasis only to the gallbladder, while 20 (61%) had additional sites of metastasis. The most common sites of additional metastasis were contralateral kidney (30%), pancreas (21%), lung (18%), adrenal (18%), and lymph nodes (9%). All patients underwent cholecystectomy. At a median follow up time of 1.5 years after cholecystectomy, 54% of patients had no evidence of disease, 14% were alive with metastasis, 23% had died from metastatic RCC, and 9% died from causes unrelated to their cancer.Gallbladder metastasis from RCC is a rare event that may occur synchronously or metachronously with most patients being asymptomatic. Clear cell carcinoma appears to be the primary pathology associated with gallbladder metastasis. High rates of bilateral RCC and pancreatic metastasis suggest novel associations in patients with RCC and gallbladder metastasis.

PurposeTo evaluate the accuracy of the sub-classification of renal cortical neoplasms using molecular signatures.Experimental designA search of publicly available databases was performed to identify microarray datasets with multiple histologic sub-types of renal cortical neoplasms. Meta-analytic techniques were utilized to identify differentially expressed genes for each histologic subtype. The lists of genes obtained from the meta-analysis were used to create predictive signatures through the use of a pair-based method. These signatures were organized into an algorithm to sub-classify renal neoplasms. The use of these signatures according to our algorithm was validated on several independent datasets.ResultsWe identified three Gene Expression Omnibus datasets that fit our criteria to develop a training set. All of the datasets in our study utilized the Affymetrix platform. The final training dataset included 149 samples represented by the four most common histologic subtypes of renal cortical neoplasms: 69 clear cell, 41 papillary, 16 chromophobe, and 23 oncocytomas. When validation of our signatures was performed on external datasets, we were able to correctly classify 68 of the 72 samples (94%). The correct classification by subtype was 19/20 (95%) for clear cell, 14/14 (100%) for papillary, 17/19 (89%) for chromophobe, 18/19 (95%) for oncocytomas.ConclusionsThrough the use of meta-analytic techniques, we were able to create an algorithm that sub-classified renal neoplasms on a molecular level with 94% accuracy across multiple independent datasets. This algorithm may aid in selecting molecular therapies and may improve the accuracy of subtyping of renal cortical tumors.

In the heart, adenosine binds to pharmacologically distinct G protein-coupled receptors (R) located on the cardiomyocyte (A1-R, A2A-R and A3-R). While the role of the A1- and A3-Rs in the heart has been clarified by selective overexpression or ablation in murine hearts, the effects of genetically manipulating the A2A-R has not been defined. Thus, we created mice overexpressing a cardiac-restricted A2A-R transgene. Mice with both low (Lo) and high (Hi) levels of A2A-R overexpression demonstrated a marked increase in cardiac contractility at 12 weeks-of-age. These changes were associated with a significantly higher systolic but not diastolic [Ca2+]i, higher maximal contraction amplitudes, maximal shortening and re-lengthening velocities, and a significantly enhanced sarcoplasmic reticulum Ca2+ uptake activity. The alterations in Ca2+ handling were associated with an increase in the level of sarcoplasmic/endoplasmic reticulum calcium ATPase (SERCA2). At 20 weeks-of-age, the effects of A2A-R overexpression on cardiac contractility diminished. The positive effects elicited by A2A-R overexpression differ from the heart failure phenotype we observed with A1-R overexpresson. Interestingly, co-expression of A2A-R TGHi, but not A2A-R TGLo, enhanced survival, prevented the development of left ventricular dysfunction and heart failure and improved Ca2+ handling in mice overexpressing the A1-R. These results suggest that adenosine-mediated signaling in the heart requires a balance between A1- and A2A-Rs – a finding that may have important implications for the ongoing clinical evaluation of adenosine receptor subtype-specific agonists and antagonists for the treatment of cardiovascular diseases.

Studies of detergent-resistant membrane (DRM) rafts in mature erythrocytes have facilitated identification of proteins that regulate formation of endovacuolar structures such as the parasitophorous vacuolar membrane (PVM) induced by the malaria parasite Plasmodium falciparum. However, analyses of raft lipids have remained elusive because detergents interfere with lipid detection. Here, we use primaquine to perturb the erythrocyte membrane and induce detergent-free buoyant vesicles, which are enriched in cholesterol and major raft proteins flotillin and stomatin and contain low levels of cytoskeleton, all characteristics of raft microdomains. Lipid mass spectrometry revealed that phosphatidylethanolamine and phosphatidylglycerol are depleted in endovesicles while phosphoinositides are highly enriched, suggesting raft-based endovesiculation can be achieved by simple (non–receptor-mediated) mechanical perturbation of the erythrocyte plasma membrane and results in sorting of inner leaflet phospholipids. Live-cell imaging of lipid-specific protein probes showed that phosphatidylinositol (4,5) bisphosphate (PIP2) is highly concentrated in primaquine-induced vesicles, confirming that it is an erythrocyte raft lipid. However, the malarial PVM lacks PIP2, although another raft lipid, phosphatidylserine, is readily detected. Thus, different remodeling/sorting of cytoplasmic raft phospholipids may occur in distinct endovacuoles. Importantly, erythrocyte raft lipids recruited to the invasion junction by mechanical stimulation may be remodeled by the malaria parasite to establish blood-stage infection.

525 Background: There have been multiple reports implicating the role of hydronephrosis (HN) as a predictor of outcome in patients diagnosed with upper tract urothelial carcinoma (UTUC). However, this was done in mixed populations (low-/high-grade) and degree of HN (DOH) was not taken into account. We evaluated the impact of severity of hydronephrosis on systemic and bladder relapse in patients with UTUC. Methods: We retrospectively reviewed the records of 141 patients with localized UTUC that underwent extirpative surgery. Preoperative imaging was used to evaluate ipsilateral DOH. We analyzed the association between DOH (none/mild vs. moderate/severe), pathological findings and oncological outcomes in high-grade vs. low-grade patients. Bladder recurrence was assessed separately from local or systemic (L/S) recurrence. Results: High-grade UTUC was present in 80% of patients, 35% had muscle-invasive disease (≥pT2), and 29% had non-organ-confined disease. At a median follow-up of 34 months (range, 1-149), 35% of patients experienced intravesical recurrence, 20% developed L/S recurrence, and 17% died of UTUC. No difference in outcomes was seen between patients without HN and mild HN. DOH was none/mild in 55% and moderate/severe in 45% of cases. In patients with high-grade UTUC, moderate/severe HN was associated with advanced pathologic stage (p