Prospective Observational Study of a Racially Diverse Group of Men on Active Surveillance for Prostate Cancer.

OBJECTIVE: To evaluate the risk upgrading of active surveillance (AS), we reviewed the outcomes of African American men (AA) after electing AS. AS is the standard of care for men with low-grade prostate cancer (PCa). AA are known to have more advanced PCa features and are more likely to die from PCa, thus subsequent disease progression for AA on AS is unclear. METHODS: A prospectively maintained AS database from the Southeast Louisiana Veterans Administration Medical Center, New Orleans, Lousiana was queried. We identified men with low- and very low-risk PCa (Gleason 3 + 3, PSA <10, ≤CT2a) who had undergone at least 2 prostate biopsies, including initial diagnostic and subsequent confirmatory prostate biopsies. Descriptive and comparative statistical analysis was performed using R version 3.5.1. RESULTS: From a total of 274 men on AS (70% AA), 158 men met inclusion criteria (104 AA [66%]). All patients underwent at least 2 biopsies, and 29% underwent 3 or more biopsies. The median follow-up was 2.7 years. At 3 years on AS protocol, 57% AA and 61% Caucasians demonstrated no evidence of upgrading or treatment. No significant difference was observed between upgrading or progression to treatment when comparing racial groups. Seven (4%) patients in this cohort died from non PCa-specific causes, but no patients demonstrated metastasis or death from PCa over the course of study. CONCLUSION: AA men with low-risk PCa can be safely followed with the same AS protocol as non-AA men. Further analysis with longer follow up is ongoing.

Robotic vs. open surgical management of ureteroenteric anastomotic strictures: technical modifications to enhance success.

Development of ureteroanastamotic strictures (UAS) after urinary diversion is not uncommon, but is challenging to treat. Poor outcomes are likely with endoscopic and radiologic management, and definitive surgical treatment can cause significant morbidity. The comparative advantages of an operative approach have not yet been fully described in the literature. We retrospectively reviewed the prospectively maintained Tulane University Department of Urology quality assurance database of 12 patients who underwent operative UAS repair between 2012 and 2018. Data were reviewed for operative approach, demographics, baseline disease characteristics, operative variables, and perioperative and pathological outcomes. Of the 12 patients analyzed, 5 underwent open repair (OR) (2 bilateral, 2 right, 1 left) and 7 underwent robotic repair (RR) (3 right, 4 left). One robotic case required conversion to open due to significant intestinal and peri-ureteral adhesions. The median ages were 59 years in OR and 60 years in RR. Two patients in each group had failed previous endoscopic repair. Median time from cystectomy to treatment of enteroanastamotic stricture was 13 months for OR and 10 months for RR (p = 0.25). Median estimated blood loss was 80 mL in both OR and RR (p = 1.0), median operative time was 260 min in OR and 255 min in RR (p = 0.13), and median hospital stay was 8 and 4 days, respectively (p = 0.06). There were two intra-operative and one post-operative complication in the OR group, one of whom required further surgical intervention, and no complications in the robotic cohort. A minimally invasive, robotic approach offers a non-inferior alternative to OR with similar outcomes for appropriately selected patients with UAS. High success rates combined with minimal morbidity may provide definitive therapy at an earlier stage of the stricture state.

Regional Differences in the Treatment of Localized Prostate Cancer: An Analysis of Surgery and Radiation Utilization in the United States.

PURPOSE: Men with localized prostate cancer have various treatment options available in their management. The optimal approach is controversial and can be influenced by multiple factors. This study aimed to investigate the influence of geographic region on the selection of treatment for prostate cancer. METHODS AND MATERIALS: Using the National Cancer Database, we identified men diagnosed with localized prostate cancer between 2010 and 2014. The United States was divided into 11 regions per the American Cancer Society Divisions. The first course of treatment was recorded as radiation therapy (RT), radical prostatectomy (RP), or active surveillance (AS). The RT subgroup consisted of patients receiving all forms of RT, including external beam and brachytherapy, or RT plus androgen deprivation therapy. The RP subgroup consisted of patients receiving RP alone or combined with RT or androgen deprivation therapy. A χ2 test was performed to assess the association between region and frequency of RT and RP. RESULTS: This study included 462,811 men with localized prostate cancer who were treated in the United States, of whom 63.46% underwent RP, 31.54% underwent RT, and 5.00% underwent AS. Significant regional differences in RP and RT were observed (P ≤ .0001). RP was used most commonly in the Midwest (75.07%) and High Plains (73.37%) regions, whereas RP was least used in the South Atlantic (59.04%) region. Similarly, RT was used most commonly in South Atlantic (40.96%) and New England (38.98%) regions and least commonly in the Midwest (24.93%) region. AS was used most in the New England (7.27%) and Midwest (6.8%) regions and least used in the High Plains (2.57%) and Mid-South (2.84%) regions. CONCLUSIONS: Regional differences exist in the United States with regard to the definitive treatment of localized prostate cancer. The etiology for these regional differences is likely multifactorial.

Robotic Pyeloplasty.

Historically, the gold standard for management of ureteropelvic junction obstruction (UPJO) has been open pyeloplasty. However, continued technological and surgical advances have ultimately led to the robotic approach. Continued advances in minimally invasive surgery have led to shorter hospital stays and hastened recovery. Here we present our step by step guide and video to robotic-assisted laparoscopic pyeloplasty.

3D-printed soft-tissue physical models of renal malignancies for individualized surgical simulation: a feasibility study.

To construct patient-specific physical three-dimensional (3D) models of renal units with materials that approximates the properties of renal tissue to allow pre-operative and robotic training surgical simulation, 3D physical kidney models were created (3DSystems, Rock Hill, SC) using computerized tomography to segment structures of interest (parenchyma, vasculature, collection system, and tumor). Images were converted to a 3D surface mesh file for fabrication using a multi-jet 3D printer. A novel construction technique was employed to approximate normal renal tissue texture, printers selectively deposited photopolymer material forming the outer shell of the kidney, and subsequently, an agarose gel solution was injected into the inner cavity recreating the spongier renal parenchyma. We constructed seven models of renal units with suspected malignancies. Partial nephrectomy and renorrhaphy were performed on each of the replicas. Subsequently all patients successfully underwent robotic partial nephrectomy. Average tumor diameter was 4.4 cm, warm ischemia time was 25 min, RENAL nephrometry score was 7.4, and surgical margins were negative. A comparison was made between the seven cases and the Tulane Urology prospectively maintained robotic partial nephrectomy database. Patients with surgical models had larger tumors, higher nephrometry score, longer warm ischemic time, fewer positive surgical margins, shorter hospitalization, and fewer post-operative complications; however, the only significant finding was lower estimated blood loss (186 cc vs 236; p = 0.01). In this feasibility study, pre-operative resectable physical 3D models can be constructed and used as patient-specific surgical simulation tools; further study will need to demonstrate if this results in improvement of surgical outcomes and robotic simulation education.

Racial Variation in the Outcome of Subsequent Prostate Biopsies in Men With an Initial Diagnosis of Atypical Small Acinar Proliferation.

BACKGROUND: African American (AA) men are known to have more aggressive prostate cancer (PCa) compared with Caucasian American men. We sought to determine predictors of subsequent detection and risk stratification of PCa in a racially diverse group of men with atypical small acinar proliferation (ASAP) on initial prostate biopsy. MATERIALS AND METHODS: A retrospective analysis was conducted on data from men with ASAP on initial prostate biopsy who subsequently received confirmatory biopsies between September 2000 and July 2015. Biopsies with more than 3 years between initial and confirmatory biopsies were excluded. Race, age, body mass index, transrectal ultrasound volume, serum prostate-specific antigen (PSA), PSA velocity, PSA density, and elapsed time between biopsies were assessed for predictive value in subsequent PCa diagnosis after an initial finding of ASAP. RESULTS: Of 106 men analyzed, 75 (71%) were AA and 31 (29%) were non-AA. Baseline variables revealed AA men had higher PSA levels, PSA velocity, and PSA density (all P < .05). PCa was diagnosed in subsequent biopsy in 42 (40%) patients without significant racial variation; 30 (40%) AA versus 12 (39%) non-AA. Of the 42 PCa patients, 25 (24%) met Epstein criteria for significant disease without racial variation; 18 (24%) AA versus 7 (23%) non-AA. Only 10 (9%) patients had any component of Gleason 4; 7 (9%) AA versus 3 (10%) non-AA. In multivariate analysis, increasing age, PSA level, and PSA density were significant predictors of PCa. CONCLUSION: AA men diagnosed with ASAP on initial prostate biopsy do not have increased risk of PCa on confirmatory biopsy compared with non-AA men.

Complete robotic repair of a renal artery aneurysm.

Although the majority of renal artery aneurysms require only observation, those that require treatment have been addressed primarily surgically or endovascularly. We report a case of surgical resection of a large, symptomatic renal artery aneurysm from an entirely robotic approach.

Identification of microRNA signature and potential pathway targets in prostate cancer.

Prostate cancer (PC) is the most common and the second leading cause of cancer-related death among American men. Early diagnosis is a prerequisite to improving therapeutic benefits. However, the current clinical biomarkers for PC do not reliably decipher indolent PC from other urogenital disorders. Thus, effective clinical intervention necessitates development of new biomarkers for early detection of PC. The present study aimed to identify the miRNA signature in organ-confined (Gleason Score 6) prostate tumors. MicroRNA (miRNA/miR) array analysis identified 118 upregulated and 73 downregulated miRNAs in microdissected tumors in comparison to matched neighboring normal prostate epithelium. The miRs-Plus-A1083, -92b-5p, -18a-3p, -19a-3p, -639, -3622b-3p, -3189-3p, -155-3p, -410, -1179, 548b-5p, and -4469 are predominantly expressed (7-11-fold), whereas miRs-595, 4490, -3120-5p, -1299, -21-5p, -3677-3, -let-7b-5p, -5189, 3-121-5p, -4518, -200a-5p, -3682-5p, -3689d, -3149 represent the most downregulated (12-113-fold) miRNAs in microdissected prostate tumors. The array expression profile of selected miRNA signature and their potential mRNA targets was validated by qRT-PCR analysis in PC cell lines. Integrated in silico and computational prediction analyses demonstrated that the dysregulated miRNA signature map to key regulatory factors involved in tumorigenesis, including cell cycle, apoptosis, and p53 pathways. The newly identified miRNA signature has potential clinical utility as biomarkers, prognostic indicators, and therapeutic targets for early detection of PC. Further studies are needed to assess the functional significance and clinical usefulness of the identified miRNAs. Impact Statement To our knowledge his is the first study of identifying miRNA signatures in microdissected indolent (Gleason score 6) prostate cancer in comparison to matched normal prostate epithelium. By employing in silico and computational prediction analysis, the study provides a landscape of potential miRNA targets and key cellular pathways involved in prostate tumorigenesis. Identification if miRNAs and their relevant targets and pathways pave the way for underpinning their mechanistic role of miRNAs in human prostate tumorigenesis, and possibly other human cancers. Importantly, the outcome of the study has important clinical implications for the management of prostate cancer, including the use of miRNA(s) as biomarkers for early detection of prostate cancer.

Technology Based Treatment for UreteroPelvic Junction Obstruction.

Surgical management of ureteropelvic junction obstruction (UPJO) has historically been performed with open pyeloplasty. With the advent of endourology, laparoscopy, and robotics, minimally-invasive techniques have been described and accepted as alternatives to open surgery. Each of these approaches has its own advantages and disadvantages, equipment needs, degree of invasiveness, and experience of the treating urologist. Advocates and critics have their own say as to their preferred technique. In this article, we review the chronological evolution of these techniques and discuss their current role in the management of UPJO.

Clinical Use of PCA3 and TMPRSS2:ERG Urinary Biomarkers in African-American Men Undergoing Prostate Biopsy.

PURPOSE: Prostate specific antigen has decreased performance characteristics for the detection of prostate cancer in African-American men. We evaluated urinary PCA3 and TMPRSS2:ERG in a racially diverse group of men. MATERIALS AND METHODS: After institutional review board approval, post-examination urine was prospectively collected before prostate biopsy. PCA3 and TMPRSS2:ERG RNA copies were quantified using transcription mediated amplification assays (Hologic, San Diego, California). Prediction models were created using standard of care variables (age, race, family history, prior biopsy, abnormal digital rectal examination) plus prostate specific antigen. Decision curve analysis was performed to compare the net benefit of PCA3 and TMPRSS2:ERG. RESULTS: Of 304 patients 182 (60%) were African-American and 139 (46%) were diagnosed with prostate cancer (69% African-American). PCA3 and TMPRSS2:ERG scores were greater in men with prostate cancer, 3 or more cores, 33.3% or more cores, greater than 50% involvement of greatest biopsy core and Epstein significant prostate cancer (p <0.01). PCA3 added to the standard of care plus prostate specific antigen model for the detection of any prostate cancer in the overall cohort (0.747 vs 0.677, p <0.0001) in African-American men only (0.711 vs 0.638, p=0.0002) and nonAfrican-American men (0.781 vs 0.732, p=0.0016). PCA3 added to the model for the prediction of high grade prostate cancer for the overall cohort (0.804 vs 0.78, p=0.0002) and African-American men only (0.759 vs 0.717, p=0.0003) but not nonAfrican-American men. Decision curve analysis demonstrated improvement with the addition of PCA3. For African-American men TMPRSS2:ERG did not improve concordance statistics for the detection of prostate cancer. CONCLUSIONS: For African-American men urinary PCA3 improves the ability to predict the presence of any and high grade prostate cancer. However, the TMPRSS2:ERG urinary assay does not add significantly to standard tools.

Racial variation in prostate needle biopsy templates directed anterior to the peripheral zone.

OBJECTIVES: African Americans (AA) have been reported to have both increased incidence and increased aggressiveness of prostate cancer (PCa) located anterior to the peripheral zone (APZ). We sought to evaluate the utility of prostate biopsies directed toward the APZ in a predominantly AA cohort. METHODS AND MATERIALS: We reviewed all patients with PCa found on biopsy schema that included needle biopsies directed at both the peripheral zone (PZ) and APZ from 2010 to 2014. Self-identified race was recorded for all patients. To evaluate the reliability of APZ-directed prostate biopsies, we performed pathologic secondary review of 25 radical prostatectomy specimens. A series of the Mann-Whitney U and Chi-square tests were used to compare variables. RESULTS: We identified 398 men, of which 277 (70%) were AA. Compared with non-AA, AA had more National Comprehensive Cancer Network-defined intermediate or high-risk (50% vs. 39%, P = 0.25) PCa. Most patients had PCa limited to the PZ only (n = 190) or in both the PZ and APZ (n = 191). For 17 patients (4%), PCa was limited only to the APZ core(s), 14 (5%) AA vs. 3 (2%) non-AA (P = 0.24). Most of these 17 patients (n = 14, 82%) had Gleason 6 disease. Patients with PCa in both the PZ and APZ had higher serum prostate-specific antigen, prostate-specific antigen density, volume of disease, and increased grade and National Comprehensive Cancer Network category (all P<0.01). Of these patients, there were no differences in race (AA = 135, 71% vs. non-AA = 56, 29%; P = 0.48). In only 21 men (11%), without racial variation, APZ tumor grade was greater than PZ. Radical prostatectomy and APZ-directed biopsies demonstrated a concordance rate of 80% (20/25), false positive rate of 8% (2/25), and false negative rate of 12% (3/25). CONCLUSIONS: APZ-directed prostate biopsies are rarely the sole location of PCa and do not show a clear racial predilection. In those men with PCa identified in both regions, the APZ biopsy did not frequently change treatment recommendations. Biopsies directed at the APZ are not of greater benefit to AA than non-AA.

Urology residents experience comparable workload profiles when performing live porcine nephrectomies and robotic surgery virtual reality training modules.

In pursuit of improving the quality of residents' education, the Southeastern Section of the American Urological Association (SES AUA) hosts an annual robotic training course for its residents. The workshop involves performing a robotic live porcine nephrectomy as well as virtual reality robotic training modules. The aim of this study was to evaluate workload levels of urology residents when performing a live porcine nephrectomy and the virtual reality robotic surgery training modules employed during this workshop. Twenty-one residents from 14 SES AUA programs participated in 2015. On the first-day residents were taught with didactic lectures by faculty. On the second day, trainees were divided into two groups. Half were asked to perform training modules of the Mimic da Vinci-Trainer (MdVT, Mimic Technologies, Inc., Seattle, WA, USA) for 4 h, while the other half performed nephrectomy procedures on a live porcine model using the da Vinci Si robot (Intuitive Surgical Inc., Sunnyvale, CA, USA). After the first 4 h the groups changed places for another 4-h session. All trainees were asked to complete the NASA-TLX 1-page questionnaire following both the MdVT simulation and live animal model sessions. A significant interface and TLX interaction was observed. The interface by TLX interaction was further analyzed to determine whether the scores of each of the six TLX scales varied across the two interfaces. The means of the TLX scores observed at the two interfaces were similar. The only significant difference was observed for frustration, which was significantly higher at the simulation than the animal model, t (20) = 4.12, p = 0.001. This could be due to trainees' familiarity with live anatomical structures over skill set simulations which remain a real challenge to novice surgeons. Another reason might be that the simulator provides performance metrics for specific performance traits as well as composite scores for entire exercises. Novice trainees experienced substantial mental workload while performing tasks on both the simulator and the live animal model during the robotics course. The NASA-TLX profiles demonstrated that the live animal model and the MdVT were similar in difficulty, as indicated by their comparable workload profiles.

Dysregulation of miR-212 Promotes Castration Resistance through hnRNPH1-Mediated Regulation of AR and AR-V7: Implications for Racial Disparity of Prostate Cancer.

PURPOSE: The causes of disproportionate incidence and mortality of prostate cancer among African Americans (AA) remain elusive. The purpose of this study was to investigate the mechanistic role and assess clinical utility of the splicing factor heterogeneous nuclear ribonucleoprotein H1 (hnRNP H1) in prostate cancer progression among AA men. EXPERIMENTAL DESIGN: We employed an unbiased functional genomics approach coupled with suppressive subtractive hybridization (SSH) and custom cDNA microarrays to identify differentially expressed genes in microdissected tumors procured from age- and tumor grade-matched AA and Caucasian American (CA) men. Validation analysis was performed in independent cohorts and tissue microarrays. The underlying mechanisms of hnRNPH1 regulation and its impact on androgen receptor (AR) expression and tumor progression were explored. RESULTS: Aberrant coexpression of AR and hnRNPH1 and downregulation of miR-212 were detected in prostate tumors and correlate with disease progression in AA men compared with CA men. Ectopic expression of miR-212 mimics downregulated hnRNPH1 transcripts, which in turn reduced expression of AR and its splice variant AR-V7 (or AR3) in prostate cancer cells. hnRNPH1 physically interacts with AR and steroid receptor coactivator-3 (SRC-3) and primes activation of androgen-regulated genes in a ligand-dependent and independent manner. siRNA silencing of hnRNPH1 sensitized prostate cancer cells to bicalutamide and inhibited prostate tumorigenesis in vivo CONCLUSIONS: Our findings define novel roles for hnRNPH1 as a putative oncogene, splicing factor, and an auxiliary AR coregulator. Targeted disruption of the hnRNPH1-AR axis may have therapeutic implications to improve clinical outcomes in patients with advanced prostate cancer, especially among AA men.

Individualized Physical 3-dimensional Kidney Tumor Models Constructed From 3-dimensional Printers Result in Improved Trainee Anatomic Understanding.

OBJECTIVE: To evaluate the effect of 3-dimensionally (3D) printed physical renal models with enhancing masses on medical trainee characterization, localization, and understanding of renal malignancy. METHODS: Proprietary software was used to import standard computed tomography (CT) cross-sectional imaging into 3D printers to create physical models of renal units with enhancing renal lesions in situ. Six different models were printed from a transparent plastic resin; the normal parenchyma was printed in a clear, translucent plastic, with a red hue delineating the suspicious renal lesion. Medical students, who had completed their first year of training, were given an overview and tasked with completion of RENAL nephrometry scores, separately using CT imaging and 3D models. Trainees were also asked to complete a questionnaire about their experience. Variability between trainees was assessed by intraclass correlation coefficients (ICCs), and kappa statistics were used to compare the trainee to experts. RESULTS: Overall trainee nephrometry score accuracy was significantly improved with the 3D model vs CT scan (P <.01). Furthermore, 3 of the 4 components of the nephrometry score (radius, nearness to collecting system, and location) showed significant improvement (P <.001) using the models. There was also more consistent agreement among trainees when using the 3D models compared with CT scans to assess the nephrometry score (intraclass correlation coefficient, 0.28 for CT scan vs 0.72 for 3D models). Qualitative evaluation with questionnaires filled out by the trainees further confirmed that the 3D models improved their ability to understand and conceptualize the renal mass. CONCLUSION: Physical 3D models using readily available printing techniques improve trainees' understanding and characterization of individual patients' enhancing renal lesions.

Stratification of Expert vs Novice Laparoscopists Using the Basic Laparoscopic Urologic Surgery (BLUS) Curriculum at a Single Institution.

PURPOSE: To assess determinants of performance applying the tasks of the Basic Laparoscopic Urologic Surgery (BLUS) skills curriculum administered at a single institution. METHODS: After obtaining institutional review board approval, fourth-year medical students, urology residents (postgraduate year 1-5), and staff attending surgeons from an academic institution were recruited. Participants were grouped by level of experience and evaluated on 4 different BLUS modules testing fundamental laparoscopic techniques from September 2012 to September 2013. Task completion time (TCT) and missed objectives were compared with previous laparoscopic experience, amount of endourological training, and scores obtained through the EDGE simulator. RESULTS: TCTs among the participants were slower and accrued greater errors in the novice group (n = 10) than in the intermediate-level (n = 9) and expert-level (n = 9) groups. Completion times on the peg transfer were 213.4, 128.1, and 108.7 seconds (p < 0.05); on the circle cutting were 182.4, 128.3, and 97.2 seconds (p < 0.05); on the clip application were 44.4, 43.2, and 38.1 seconds (p = 0.08); and on the suturing were 286.1, 177.3, and 123.6 seconds (p < 0.05) for novice, intermediate, and expert groups, respectively. When past laparoscopic numbers of participants were compared with TCTs, a positive correlation of R(2) = 0.39 was seen, signifying a relationship between number of laparoscopic cases and TCT outcomes. CONCLUSION: Performance on the EDGE simulator device during the BLUS modules significantly correlated with the amount of laparoscopic experience. Increase in the years of experience and number of laparoscopic cases led to faster and more accurate TCTs.

Active surveillance of prostate cancer in African American men.

Active surveillance (AS) is a treatment strategy for prostate cancer (PCa) whereby patients diagnosed with PCa undergo ongoing characterization of their disease with the intent of avoiding radical treatment. Previously, AS has been demonstrated to be a reasonable option for men with low-risk PCa, but existing cohorts largely consist of Caucasian Americans. Because African Americans have a greater incidence, more aggressive, and potentially more lethal PCa than Caucasian Americans, it is unclear if AS is appropriate for African Americans. We performed a review of the available literature on AS with a focus on African Americans.

Physical models of renal malignancies using standard cross-sectional imaging and 3-dimensional printers: a pilot study.

OBJECTIVE: To construct high-fidelity, patient customized, physical, 3-dimensional (3D) models of renal units with enhancing renal lesions identified on cross-sectional imaging, which may aid patients, trainees, and clinicians in their comprehension, characterization, localization, and extirpation of suspicious renal masses. METHODS: Specialized software was used to import patient's diagnostic computerized tomography cross-sectional imaging into 3D printers and create physical 3D models of renal units with enhancing in situ lesions. Patients and trainees had the opportunity to manipulate the individualized model before surgical resection. Sterolithography additive manufacturing, a technique in which an ultraviolet laser is used to cure a photosensitive resin in sequential horizontally oriented layers, was used to build the models (Medical Modeling Inc., Golden, CO). Normal renal parenchyma was printed with a clear translucent resin, and red translucent resin delineated suspicious lesions. Renal vasculature and the proximal collecting system were printed in some models. RESULTS: We constructed 5 physical models of renal units with suspected malignancies before surgery. All patients successfully underwent partial nephrectomy (4 robotic and 1 open). Average ischemia time was 21 minutes, nephrometry score was 6.8, and all margins were negative. Anecdotally, patients, their families, and trainees consistently stated that the models enhanced their comprehension of the renal tumor in relation to surrounding normal renal parenchyma and hilar structures and improved understanding of the goals of the surgery. CONCLUSION: Preoperative physical 3D models using available printing techniques can be constructed and may potentially influence both patients' and trainees' understanding of renal malignancies.

Neoplastic reprogramming of patient-derived adipose stem cells by prostate cancer cell-associated exosomes.

Emerging evidence suggests that mesenchymal stem cells (MSCs) are often recruited to tumor sites but their functional significance in tumor growth and disease progression remains elusive. Herein we report that prostate cancer (PC) cell microenvironment subverts PC patient adipose-derived stem cells (pASCs) to undergo neoplastic transformation. Unlike normal ASCs, the pASCs primed with PC cell conditioned media (CM) formed prostate-like neoplastic lesions in vivo and reproduced aggressive tumors in secondary recipients. The pASC tumors acquired cytogenetic aberrations and mesenchymal-to-epithelial transition and expressed epithelial, neoplastic, and vasculogenic markers reminiscent of molecular features of PC tumor xenografts. Our mechanistic studies revealed that PC cell-derived exosomes are sufficient to recapitulate formation of prostate tumorigenic mimicry generated by CM-primed pASCs in vivo. In addition to downregulation of the large tumor suppressor homolog2 and the programmed cell death protein 4, a neoplastic transformation inhibitor, the tumorigenic reprogramming of pASCs was associated with trafficking by PC cell-derived exosomes of oncogenic factors, including H-ras and K-ras transcripts, oncomiRNAs miR-125b, miR-130b, and miR-155 as well as the Ras superfamily of GTPases Rab1a, Rab1b, and Rab11a. Our findings implicate a new role for PC cell-derived exosomes in clonal expansion of tumors through neoplastic reprogramming of tumor tropic ASCs in cancer patients.

Learning curve assessment of robot-assisted radical prostatectomy compared with open-surgery controls from the premier perspective database.

INTRODUCTION: The primary aims of this study were to assess the learning curve effect of robot-assisted radical prostatectomy (RARP) in a large administrative database consisting of multiple U.S. hospitals and surgeons, and to compare the results of RARP with open radical prostatectomy (ORP) from the same settings. MATERIALS AND METHODS: The patient population of study was from the Premier Perspective Database (Premier, Inc., Charlotte, NC) and consisted of 71,312 radical prostatectomies performed at more than 300 U.S. hospitals by up to 3739 surgeons by open or robotic techniques from 2004 to 2010. The key endpoints were surgery time, inpatient length of stay, and overall complications. We compared open versus robotic, results by year of procedures, results by case volume of specific surgeons, and results of open surgery in hospitals with and without a robotic system. RESULTS: The mean surgery time was longer for RARP (4.4 hours, standard deviation [SD] 1.7) compared with ORP (3.4 hours, SD 1.5) in the same hospitals (p<0.0001). Inpatient stay was shorter for RARP (2.2 days, SD 1.9) compared with ORP (3.2 days, SD 2.7) in the same hospitals (p<0.0001). The overall complications were less for RARP (10.6%) compared with ORP (15.8%) in the same hospitals, as were transfusion rates. ORP results in hospitals without a robot were not better than ORP with a robot, and pretreatment co-morbidity profiles were similar in all cohorts. Trending of results by year of procedure showed no differences in the three cohorts, but trending of RARP results by surgeon experience showed improvements in surgery time, hospital stay, conversion rates, and complication rates. CONCLUSIONS: During the initial 7 years of RARP development, outcomes showed decreased hospital stay, complications, and transfusion rates. Learning curve trends for RARP were evident for these endpoints when grouped by surgeon experience, but not by year of surgery.