D. Barski1, H. Gerullis2, A. Winter2, I. Pintelon3, J-P. Timmermans3, A. Ramon4, M. Boros5, G. Varga5, T. Otto1
1Urology, Lukas Hospital Neuss, Germany
2Urology, School of Medicine and Health Sciences, Carl Von Ossietzky University, Germany
3Laboratory of Cell Biology and Histology, University of Antwerp, Belgium
4ITERA, International Tissue Engineering Research Association, Belgium
5Institute of Experimental Surgery, University of Szeged, Hungary
Introduction & Objectives: Different autolog, xenolog and synthetic materials were tested for the repair of urinary tract defects. Amniotic membrane (AM) is assumed to have several unique characteristics allowing its perfect ingrowth in the surrounding tissue. In this animal rat study we first applied human AM for the repair of bladder defects. Material & Methods: Following the IDEAL recommendations of surgical innovation preliminary animal study was conducted to show the feasibility of the method. In a total of 26 sprague male rats a small defect at the bladder dome was set and repaired by grafting with a multilayer cryopreserved AM from human caesarian section. Bladder volume capacity and leakage after grafting were measured. Peri- and early postoperative complications were assessed. Histological and immunohistological analyses were performed to look for the degradation of AM, graft rejection and the ingrowth of surrounding tissue 7, 21 and 42 days after the implantation. Results: Two rats died due to sepsis. All other rats survived, had no severe complications and showed no signs of leakage. The bladder capacity did not change over time. No signs of AM degradation were found after 42 days. The initial inflammation reaction reduced significantly to almost normal values in the amnion group. The smooth muscle staining increased over time. Conclusions: AM seems to be a durable and hypoallergenic graft. Further animal and human studies are necessary to proof the possible indications.
Urology, Mount Sinai, New York, USA
PURPOSE: To prevent complications following trans rectal ultrasound guided prostatic needle biopsy (trus/pnb) through the use of targeted antimicrobial therapy. METHODS: Using a modification of previously published techniques we initiated a system of rectal swab cultures prior to trus/pnb. Rectal swabs were taken from patients who were scheduled for trus/pnb and placed in vials containing Ciprofloxin 10 micrograms/ml. These vials were transported to the microbiology lab for analysis. Prophylaxis with Ciprofloxin500mg BID starting the day prior to the biopsy and continued for 3 days was used in all patients who were negative for Ciprofloxin resistance. Those patients whose cultures were positive were placed on targeted antibiotics as dictated by sensitivity testing. RESULTS: 540 patients who underwent trus/pnb since May 2012 had rectal swabs taken.55 patients (10%), had positive cultures for Ciprofloxin resistance. These patients were placed on antibiotics as determined by the sensitivity testing. CONCLUSION: To date only one patient developed fever/uti which was if short duration and easily treated. Given the reported incidence of post trus/pnb infectious complications of 3% using standard fluoriquinolone prophylaxis, the use of pre biopsy rectal swab cultures is an effective method of reducing infectious complications.
An analysis of expression of druggable targets and prostate cancer disease signatures in 2,978 patients with adverse pathology after radical prostatectomy: initial results from the Decipher GRID
E. Davicioni, J. Lehrer, N. Erho, H. Al-Deen Ashab, M. Takhar, L. Lam, P. Wood, M. Alshalafa
Research & Development, GenomeDx Biosciences, Canada
The Decipher® prostate cancer classifier is a genomic test used for local therapy treatment decision-making. Unlike other tests, Decipher uses a global RNA profiling assay, which generates genome-wide expression data for each patient. This data has been anonymized and made available for research in the Decipher GRIDTM. Here we report an initial analysis further characterizing the genomic landscape of localized prostate cancer. The expression and distribution of 697 genes, 31 prostate cancer disease signatures for metastasis risk, proliferation, luminal/basal, small cell and AR signalling were examined across 2,978 radical prostatectomy tumors with adverse pathology tested with Decipher and available in the GRID. For the 697 genes, expression distribution was characterized and high and low expression were defined using thresholds based on median +/- 1.5*1.48*MAD (median absolute deviation). Genes from 31 published prostate cancer signatures were adapted to the Decipher platform and scores were calculated. Up to 11% of patients have high expression of one or more druggable targets including immune checkpoint inhibitors (PD1, PDL1) and growth receptors (c-MET, EGFR, HER). Clustering of scores for 31 signatures revealed several clear groupings of patients. About 20% of patients consistently had high scores for all the metastasis risk signatures and low-average AR signalling scores. About 10% of patients had high scores for the proliferation signatures but low metastasis risk scores. Tumors with low AR signalling scores were enriched with high basal and small cell signature scores whereas most luminal tumors had higher AR signalling. Since every patient who has received the Decipher test also has a genome-wide expression profile, the Decipher GRID allows researchers to evaluate on a systematic, population-level the expression of genes and signatures that may guide future therapies. This rich genomic resource is being made available on a research use only basis to researchers and to clinicians seeking to but understand prostate cancer in order to advance precision medicine.
Development and validation of a prostate cancer genomic signature that predicts early ADT treatment failure following radical prostatectomy
E. Davicioni1, J. Karnes2, H. Al-Deen Ashab1, V. Choerung1, M. Alshalafa1, N. Erho1, K. Yousefi1, A. Ross3, F. Feng5, R. Den4, A. Dicker4, T. Lotan3, E. Klein6, E. Schaeffer7
1Research & Development, GenomeDx Biosciences, Canada
2Urology, Mayo Clinic, USA
3Urology, Johns Hopkins, USA
4Radiation Oncology, Thomas Jefferson, USA
5Radiation Oncology, University of California San Francisco, USA
6Urology, Cleveland Clinic, USA
7Urology, Northwestern University, USA
Androgen deprivation therapy (ADT) is one of the main treatment options for locally advanced and metastatic prostate cancer. Neuroendocrine prostate cancer (NEPC) is inherently less sensitive or even resistant to ADT. NEPC can be observed de novo (e.g., small cell prostate cancer) but more commonly arises after exposure to ADT. We hypothesized that a gene expression signature of NEPC when measured in primary tumor specimens (RP) of prostatic adenocarcinoma may be useful for predicting patients with innate resistance to ADT. Expression profiles of 1,212 prostate cancer patients treated with RP were retrieved from the Decipher genomic resource information database (GRIDTM). A training set consisted of ADT-treated patients matched using propensity scores to non-ADT treated patients from a case-control study (n=284) was used to develop ADT resistant signature (ARS). A feature set of 1,632 genes related to NEPC was filtered using a generalized linear model. ADT was incorporated as an interaction term with gene expression while adjusting for confounding variables. Two validation sets from two independent institutions (n=234, n=374) were used for evaluating the ARS model. Kaplan Meier and multivariable Cox regression analyses were used to compare survival differences between ‘treated’ and ‘untreated’ patients. The primary endpoint was metastasis. In multivariable analysis adjusting for confounding variables including CAPRA-S, Decipher, ARS validated with a significant interaction with ADT treatment (p0.05) in both validation cohorts. In un-treated patients there was no difference in metastasis-free survival (p=0.773). In patients receiving ADT, patients with the lowest ARS scores (about 60% of results) had improved metastasis-free survival with ADT, whereas patients with the highest ARS scores (about 15% of results) had worse metastasis-free survival (p0.001). Patients with high Decipher risk of metastasis and high ARS score are at higher risk of failing hormonal treatment. ARS may allow for identification of patients that may be optimal candidates for chemohormonal therapy rather than ADT or trials of novel systemic agents.
F. Gaylis1,2, E. Cohen1, R. Calabrese1, H. Prime1, P. Dato1, C. Kane2
1Urology, Genesis Healthcare Partners, USA
2Urology, University of California San Diego, USA
Objective: To measure past active surveillance (AS) adoption rates, institute the best practice, and measure the AS adoption rates following implementation. We report our findings over a three-year period. Methods: Patient Prostate Needle Biopsy (PNB) and treatment data from the period August 2011 to August 2014 were retrieved from an integrated EMR (Allscripts) and stored in a Microsoft Access database for analysis. Structured data were queried using the automated software program WizMDTM and unstructured data were abstracted by manual review. AS adoption was calculated according to four different selection criteria. Between 2013 and 2014, physicians at Genesis Healthcare Partners (GHP) underwent an educational training program on the UCSD/GHP AS best practice for managing low-risk prostate cancer patients and were provided report cards on their AS adoption and comparative reporting. Results: AS adoption increased for the three years of the study. AS adoption for all newly diagnosed patients managed at GHP increased from 12.9% to 14.74%. AS adoption for patients with low risk prostate cancer (as defined by the National Comprehensive Cancer Network) increased from 31.90% to 58.46% from year 1 to year 3 of the study (p0.001), and AS adoption for the most strict (restrictive) criteria increased from 43.75% to 82.61% (p0.001) after the educational and comparative reporting intervention. Conclusion: These data highlight the potential benefit of physician education and comparative reporting to enhance AS adoption. AS adoption rates vary according to selection criteria used for analysis. Carefully selected outcomes from evidence-based guidelines have the potential to enhance medical quality.
Community Based Prostate Cancer Presentation and Diagnosis Coinciding with Screening Recommendations
F. Gaylis1,2, J. Choi2, P. Dato1, E. Cohen1, R. Calabrese1, H. Prime1, A. Rosenbaum1, A. Karim Kader2
1Urology, Genesis Healthcare Partners, USA
2Urology, University of California San Diego, USA
Background Rates of metastatic prostate cancer (PCa) presentation have dropped during the prostate specific antigen (PSA) screening era. The impact of the United States Preventative Services Task Force (USPSTF) recommendations against screening has not been established. Methods Characteristics of men presenting for an elevated PSA at a community Urology Practice from August 2011 to August 2015 were prospectively collected. A retrospective analysis of radical prostatectomy (RP) outcomes during this period was performed. Kruskal-Wallis rank sum tests were used to compare outcomes. Results Men referred for elevated PSA decreased from 933 in year 1 to 816 by year 4 (12.5% decrease) with a concomitant reduction in biopsies performed in newly referred men from 461 to 356 (22.8% decrease). Median pre-biopsy PSA increased from 7.0 ng/ml to 8.2 ng/ml (p=0.0001) with a rise in the proportion of men having PSAs 10 from 28.1% to 36.8%. The first-time biopsy (for elevated PSA) positivity rate increased from 48.4% to 62.4% with a rise in the proportion of men having Gleason score ≥ 7 from 51.6% to 69.7% (p=0.0001). Of the 578 men who underwent radical prostatectomy, there was a 19.4% increase in Gleason ≥ 7 tumors (p=0.01) and a 21.7% increase in higher stage, pT3 disease (p=0.23). ConclusionsOur findings suggest the diagnosis of a more aggressive PCa phenotype coinciding the USPTSF recommendations against PSA screening. While a reduction in PSA screening is possibly desirable in the short term, should this trend continue we may miss the window of curability for many men.
PAPAVERINE HYDROCHLORIDE LOADED NANOFIBROUS BIODEGRADABLE MEMBRANES FOR URETHRAL RECONSTRUCTION SURGERY
E. Guven1, P. Hosseinian1, E.O. Guven2
1Nanotechnology and Nanomedicine Division, Hacettepe University, Turkey
2Urology, A.Y. Ankara Oncology Research and Training Hospital, Turkey
Urethral reconstructive surgeries (URSs) such as hypospadias repair or urethroplasties strongly rely on functional wound healing to be successful. Good perfusion with control of excess inflammation are the key factors in wound healing. That is especially true for urethral wound healing where perfusion is unexpectedly sparse and excess inflammation ends with stricture formation. Electrospinning is an effective technique which can be utilized to produce useful ultrafine nanofibers. Due to their large surface area, nanofibers have received much interest in various applications such as medical textiles, filtration and drug delivery systems. In this study, papaverine hydrochloride loaded poly (lactic acid) (PLA) nanofibrous membrane was successfully fabricated via electrospinning technique as a controlled drug delivery system to be used in URSs. This biodegradable material was designed to wrap around the urethra at the urethral reconstruction site before the wound closure. Phosphodiesterase-5 and 4 inhibitors have vasodilator and antiinflammatory effects, respectively. In order to control the inflammatory process while improving local tissue perfusion, papaverine hydrochloride, a safe and nonspechific phosphodiesterase inhibitor, was loaded into membrane. We assume that controlled release of papaverine hydrochloride will improve urethral healing process and decrease the rate of complications. Nanofibrous membranes were characterized according to their structural and morphological properties. Our results demonstrate that papaverine hydrochloride loaded PLA nanofibrous membranes could have good potential in urethral repair. Further in vivo studies have been planned to demonstrate the efficacy of these nanofibrous membranes as controlled drug delivery systems for urethral reconstruction surgery.
ASYMPTOMATIC URINARY RETENTION IN ELDERLY WOMEN UPON ADMISSION TO THE INTERNAL MEDICINE DEPARTMENT: A PROSPECTIVE STUDY
D Justo1,4, N. Schwartz1, E. Dvorkin1, I. Gringauz2, A. Groutz3,4
1Geriatrics, Sheba Medical Center, Israel
2Internal Medicine T, Sheba Medical Center, Israel
3Urogynecology, Lis Maternity Hospital, Sourasky Medical Center, Israel
4Sackler School of Medicine, Tel-Aviv University, Israel
Purpose: To assess the incidence and associated risk factors of asymptomatic urinary retention in elderly women upon admission to the Internal Medicine department. Methods: 202 consecutive elderly women (mean age: 84.4±5.7 years) who were admitted to four Internal Medicine departments at a tertiary medical center were prospectively enrolled. All patients underwent post-void residual (PVR) urine measurements on the morning following admission day by using a portable ultrasound bladder scan. Asymptomatic urinary retention was defined as PVR200ml without lower urinary tract symptoms, or abdominal pain, in two consecutive measurements. Results: Asymptomatic urinary retention was diagnosed in 29 (14.4%) women (mean PVR: 353.1+155.2ml; range: 200-712ml). The mean age, prevalence of chronic diseases, and the rates of opioids and anticholinergics usage were similar in women with versus without asymptomatic urinary retention. A binary logistic regression analysis showed that asymptomatic urinary retention was significantly and independently associated with low mobility, measured by the functional independence measure (FIM) scale (odds ratio=0.7, 95% confidence interval 0.6-0.9, p=0.026), and hypothyroidism (odds ratio=2.4, 95% confidence interval 1.0-5.8, p=0.049). Among 174 (86.1%) patients in whom thyroid stimulating hormone (TSH) serum levels were measured, a statistically significant correlation was demonstrated between the TSH levels and PVR (r=0.177, p=0.019). Conclusions: Asymptomatic urinary retention in elderly women upon admission to the Internal Medicine department is not infrequent and is independently associated with hypothyroidism and low mobility. PVR measurements should therefore be considered in all women with a low level of mobility and/or hypothyroidism upon admission to the Internal Medicine department.
IsoPSA: INITIAL CLINICAL PERFORMANCE EVALUATION OF A NOVEL STRUCTURE-BASED BIOMARKER FOR PROSTATE CANCER IN A MULTICENTER PROSPECTIVE TRIAL FOR GLEASON ≥ 7.
E. Klein1, M. Stovsky1,2, R. Di Loreto3, J. Hafron3, K. Kernan3, K. Manickam4, V. Kipnis5
1Cleveland Clinic, USA
2Cleveland Diagnostics Inc., USA
3Michigan Institute of Urology, USA
4Chesapeake Urology Research Associates, USA
5Biometery Research Group - National Cancer Institute, USA
INTRODUCTION: We conducted preliminary evaluation of one multivariate model centered on IsoPSA™, a novel structure-focused protein biomarker to assess potential discrimination of high-grade (Gleason≥7) from benign or low-grade (Gleason=6) patients. In this multicenter prospective trial we provide performance data compared with biopsy reports. METHODS: 132 plasma samples were obtained from multiple clinical sites, collected within 30 days prior to prostate biopsy from patients with blood PSA between 2 and 26 ng/ml. IsoPSA was evaluated against 12 core TRUS biopsy results as gold standard. The prevalence of high-grade patients in the sample cohort was 34%. Multivariate logistic regression model included the IsoPSA test parameter, KP, total PSA, age, and prostate volume. RESULTS: The model predictions are subdivided into low risk, intermediate risk, and high risk. For both low and high risk cohorts, ROC analysis showed AUC=0.85. For the probability parameter value, KP < 15%, a cohort of patients with very low probability for Gleason ≥ 7 could be identified with SN = 97%, SP = 47%, NPV = 97%, and PPV = 49%. In the same model, KP > 64% identified a second patient cohort at high risk with SN = 47%, SP = 96%, NPV = 78%, and PPV = 86% In comparison, serum PSA ROC analysis showed AUC=0.61, NPV=68%, PPV=35%, at PSA=4.0. Using KP for patient selection would have resulted in 97% avoided biopsies for the low risk cohort and a reduction of 52% of unnecessary biopsies with no missed high risk patients. CONCLUSIONS: Combining IsoPSA with other clinically relevant parameters yields high performance models to stratify patients into low and high risk cohorts to improve patient selection for biopsy.
E. Kord1, A. Neheman1, A. Zisman1, A. Buchler2, R. Tepper3
1Department of Urology, Assaf Harofeh Medical Center, affiliated to the Sackler Faculty of Medicine, Tel-Aviv University, Israel
2Department of Urology, Meir Medical Center, affiliated to the Sackler Faculty of Medicine, Tel-Aviv University, Israel, Israel
3Department of gynecology, Meir Medical Center, affiliated to the Sackler Faculty of Medicine, Tel-Aviv University, Israel, Israel
Purpose Fetal urinary tract abnormalities (UTA) are a common finding on antenatal ultrasound examination presenting in 1-2% of fetuses. Recently a multidisciplinary consensus of prenatal and postnatal urinary tract dilatation stratified this cases to risk groups and accordingly to postnatal management recommendations. In this study we present the accuracy of prenatal diagnosis of UTA Methods We retrospectively reviewed the medical records of mothers and neonates with UTA referred to our prenatal clinic between 2010-2014, 59 cases were included. Hydronephrosis was defined as renal pelvis antero-posterior diameter of 7 mm or greater. Hydroureteronephrosis/megaureter was defined if the distal ureter was observed, regardless of the diameter. Double collecting system, ureterocele, multicystic dysplastic kidney and posterior urethral valve were diagnosed upon appearance. Neonates underwent ultrasound examination one month after birth, the finding on this examination was the reference point to evaluate the accuracy of prenatal US. Both second trimester and follow up prenatal findings are compared to postnatal findings Results: Hydronephrosis is diagnosed accurately in 71%. A double collecting system is diagnosed accurately in 64%. Post natal hydroureteronephrosis is diagnosed prenatally in only 44% of cases. Unilateral hydroureteronephrosis are most commonly misinterpreted as hydroneprhosis and vise versa. There was no difference in overall accuracy of 2ndtrimester prenatal diagnosis and prenatal follow-up (61% vs 58). Conclusion: Prenatal US screening has an overall accuracy of 60%, lower than expected. The most common misdiagnosis is megaureter which is frequently diagnosed as unilateral hydronephrosis.
Minimally invasive approach for treatment of seminal vesicle cyst associated with ipsilateral renal agenesis
E. Kord1, A. Neheman1, A. Zisman1, A. Darawshe2, N. Dally3, P. Noh4
1Department of Urology, Assaf Harofeh Medical Center, affiliated to the Sackler Faculty of Medicine, Tel-Aviv University, Israel
2Department of Urology, Meir Medical Center, affiliated to the Sackler Faculty of Medicine, Tel-Aviv University, Israel
3Department of Urology, Galilee Medical Center, Israel
4Department of Urology, Cincinnati Children's Hospital Medical Center, USA
Purpose: Seminal vesicle cyst associated with ipsilateral renal agenesis is a rare abnormality of the urinary tract. This condition is usually diagnosed in the third to fifth decade of life due to urinary symptoms that arise from the pelvic mass affect. Patients usually present with irritative voiding urinary symptoms and are often misdiagnosed. We present our experience with minimally invasive surgery for this rare condition. Methods Between the years 2008-2015 we operated on 4 cases that presented with symptomatic Seminal vesicle cyst and ipsilateral renal agenesis. Three patients were operated in a laparoscopic approach and one in a robotic approach. Patient`s charts and surgical results were reviewed. Results: All patients presented with symptoms of urinary urgency and frequency. One patient suffered from recurrent urinary retention. One patient presented with recurrent epididymitis eventually forming an epididymal abscess.In all cases an abdominal US was the initial imaging test. Abdominal CT was performed in all cases and in two cases an additional MRI. Mean diameter of the seminal vesicle was above 7 cm in all cases. Mean operating age was 20 years. Median hospitalization time was 4 days (2-14). Mean follow up period was 2.9 years (range 0.6-3.6 years) and all patients reported on clinical post-operative improvement. During follow up, one patient required an additional operation due to symptom recurrence with pelvic cystic findings two years post operatively. Conclusion A Minimally invasive approach for the treatment of seminal vesicle cyst allows excellent access to the pelvis with better vision and good surgical results.
Multidetector Computed Tomographic Urography (MDCTU) its possible role in the diagnosis of Upper Tract Urothelial Cancer in high-risk patients.
S. Kravchick1, E. Cherniavsky2, L. Linova2
1Urology, Assaf Harofeh Medical Center, Israel
2Roentgenology, Barzilai Medical Center, Israel
50 years who presented with hematuria. Materials and Methods We reviewed the radiologic reports of 173 patients who underwent evaluation for hematuria. We compared MDCTU findings with the results of ureteroscopy. We also looked for predictive factors for upper tract urothelial cancer (UTUC).Results. As a result, 140 patients met the inclusion criteria. In 17% (n=24) of our patients MDCTU suspected UTUC (n-8) and bladder cancer(n-16). Ureteroscopy had diagnosed UTUC in 9 patients: 6 with suspicious lesions on MDCTU and three additional. MDCTU had a sensitivity of 66.7%, specificity - 98.5%/.Logistic regression model revealed five strong predictors for UTUC: positive/atypical cytology, recurrent hematuria, MDCTU signs, age and Warfarin treatment. Conclusions We found that MDCTU can effectively identify patients in whom further endoscopy is unnecessary. Otherwise, elder patients with positive/atypical cytology and recurrent hematuria, who have positive MDCTU signs and take Warfarin, should undergo endoscopic evaluation. "ObObjectives In this study, we evaluated the role of MDCTU in patients50 years who presented with hematuria. Materials and Methods We reviewed the radiologic reports of 173 patients who underwent evaluation for hematuria. We compared MDCTU findings with the results of ureteroscopy. We also looked for predictive factors for upper tract urothelial cancer (UTUC). Results. As a result, 140 patients met the inclusion criteria. In 17% (n=24) of our patients MDCTU suspected UTUC (n-8) and bladder cancer(n-16). Ureteroscopy had diagnosed UTUC in 9 patients: 6 with suspicious lesions on MDCTU and three additional. MDCTU had a sensitivity of 66.7%, specificity - 98.5%/.Logistic regression model revealed five strong predictors for UTUC: positive/atypical cytology, recurrent hematuria, MDCTU signs, age and Warfarin treatment. Conclusions We found that MDCTU can effectively identify patients in whom further endoscopy is unnecessary. Otherwise, elder patients with positive/atypical cytology and recurrent hematuria, who have positive MDCTU signs and take Warfarin, should undergo endoscopic evaluation. jectives In this study, we evaluated the role of MDCTU in patients 50 years who presented with hematuria. Materials and Methods We reviewed the radiologic reports of 173 patients who underwent evaluation for hematuria. We compared MDCTU findings with the results of ureteroscopy. We also looked for predictive factors for upper tract urothelial cancer (UTUC). Results. As a result, 140 patients met the inclusion criteria. In 17% (n=24) of our patients MDCTU suspected UTUC (n-8) and bladder cancer(n-16). Ureteroscopy had diagnosed UTUC in 9 patients: 6 with suspicious lesions on MDCTU and three additional. MDCTU had a sensitivity of 66.7%, specificity - 98.5%/.Logistic regression model revealed five strong predictors for UTUC: positive/atypical cytology, recurrent hematuria, MDCTU signs, age and Warfarin treatment. Conclusions We found that MDCTU can effectively identify patients in whom further endoscopy is unnecessary. Otherwise, elder patients with positive/atypical cytology and recurrent hematuria, who have positive MDCTU signs and take Warfarin, should undergo endoscopic evaluation.
ASSESSMENT OF NEEDLE TIP DEFLECTION DURING TRANSRECTAL GUIDED PROSTATE BIOPSY- IMPLICATIONS FOR TARGETED BIOPSIES
D. Halstuch, D. Margel, J. Baniel, R. Ozalvo, S. Tuval, Y. Ber
Division of Urology, Rabin Medical Center, Israel
Background: In the present era of targeted prostate biopsy precise sampling of the region of interest is critical. Objective: To measure real-time the needle tip deflection during TRUS prostate biopsy and evaluate predictors for needle tip deflection. Design, setting, and participants: Analysis of 568 prostate biopsies obtained from 51 consecutive patients who underwent a standard 12-core TRUS guided prostate biopsy. TRUS guided prostate biopsies were performed using BK flex500, with a side-fire biplane probe. Each biopsy core image was captured. And clinical data were recorded prospectively. Intervention: The angle between the expected trajectory of the needle and actual needle course was measured using the longitudinal view of the captured image. Needle deflection was then calculated assuming a 90 degree triangulation. Outcome measurements and statistical analysis: median and interquartile needle deflection measurement stratified by side and location (apex, midgland, base) are reported. Univariable and multivariable linear regressions analysis were performed. Results and limitations: The overall median needle tip deflection was 1.77 mm (IQR 1.35-2.47). Location did not significantly alter needle deflection measurements. On multivariable linear regression analysis higher prostate volume (0.07 95%CI 0.04-0.011 ; p 0.001) and the right sided biopsy (0.11 95%CI 0.05- 0.34; p = 0.010) emerged as predictors of higher needle tip deflection. Conclusions: To the best of our knowledge this is the first study to measure needle tip deflection during TRUS guided prostate biopsies. We demonstrated that larger prostate size and side may affect the accuracy of biopsies. These results may have clinical implication to those performing targeted biopsies.
An audit of Intermittent anti-androgen monotherapy compared to GNRH treatment
T. Oliver, D. Berney, T. Philp, G. Shaw
Barts Institute of Cancer, and Whipps Cross Hospital, London, United Kingdom
Abstract: A case report of a Gleason 4+4 patient, who self-medicated on intermittent flutamide with 14 cycles of 3 months on 3 months off and was surviving at 14 years,cast doubt on conventional wisdom that intermittently androgen blockade should include an LHRH blocking agent. Anti-androgen(aa) monotherapy was thought to be dangerous as on treatment testosterone rises.. Following this case others already on AA continuously were recruited to our then ongoing audit of outcomes from use of intermittent hormone therapy(Lane 2004). This abstract records their outcome and compares it with those treated with conventional GNRH monotherapy or maximum androgen blockade Results: Between 1997 and 2007 111 patients sort advice about intermittent hormone therapy having started on some form of endocrine treatment. 46 MO patients received GNRH regime and 33 receive aa monotherapy (M0=31). Provided PSA was below 4 they were eligible for entry. Median pre-treatment PSA was 22 (range 0.4-237) compared to 22 (range 3.7-402) in MO GNRH groups. Over all survival was 87% ,at 5 year and 78% at 8 years and continuing to respond on protocol 66% at 5 yrs, 57% at 8 compared to 77/56% at 5 and 54/41% at 8 years in M0 GNRH treated group Conclusion: Non-randomised selection in this cohort makes it difficult to draw strong conclusions. As overall survival is significantly better than with GNRH regimens, given recent progress in using Bipolar Androgen Therapy to reverse and Androgen resistance, an exploratory randomised phase 2 trial comparing GNRH against aa monotherapy in patients presenting with over expression of androgen receptor and below normal age-corrected serum testosterone is under consideration
P. Rasner, D. Pushkar, K. Kolontarev, D. Kotenko
Urology, Moscow State University of Medicine and Dentistry, Russia
Objective Prostate cancer doesn’t have any specific symptoms at an early stage. Most of those patients come to urologists with complaints to micturition disorders. Some of them still have this complains after the radical prostatectomy. In our study we were going to learn if there any dependence of postoperative LUTS on the chosen surgery technique. Materials Results of 512 da Vinci and 71 retropubic radical prostatectomy cases were analyzed starting from December 2008. (Mean age 61,2±6,3 years). 290 patient of RARP group (56,6%) and 36 (52%) of RRP group had some LUTS before the procedure. IPSS scores were 9,3±3,1 и 10,3±3,3 in those groups, respectively. Very high scores from 25 to 35 were revealed at 2,7% RARP and 4,5% RRP patients. Control evaluation was performed one year after the surgery. Results When comparing the two groups, a statistically significant difference (p 0.05) was noted in prevalence of LUTS one year after the prostatectomy. In RARP group LUTS were registered in 9,1% of patients. In RRP group the prevalence of LUTS was significantly higher - up to 58,9%. It should be noted, we don’t discuss symptoms of incontinence in our analysis. The most important fact – 30,4% of patients in RRP group and only 2,5% in RARP group have got LUTS «de novo». ) (pic. 1) Conclusions Robotic prostatectomy is associated with low chance of LUTS and «LUTS de novo» one year after the surgery and it is not true for RRP. The difference is statistically significant. (p 0.05)
SEXUAL REHABILITATION AFTER ROBOTIC AND RETROPUBICAL PROSTATECTOMY. OBJECTIVE AND SUBJECTIVE ANALYSIS
P. Rasner, D. Pushkar, D. Kotenko, K. Kolontarev
Urology, Moscow State University of Medicine and Dentistry, Russia
Objective The main goal of sexual rehabilitation after radical prostatectomy is to achieve an erection of the penis sufficient for sexual intercourse. In real clinical practice we are short of measurement methods of patient’s sexual satisfaction after the radical prostatectomy. Materials It was a retrospective nonrandomized trial which was conducted in 583 radical prostatectomies performed in a single clinical center. (Mean age 61,2±6,3 years). All patients had localized prostate cancer and were divided in two groups – 512 were undergone the da Vinci procedure and 71 - retropubic radical prostatectomy. All of them were done from December 2008 to December 2013 . 17,5% of patient in RARP group and 24,62% in RRP group had no sexual activity before the procedure. Good initial sexual condition (IIEF ≥17) was registered in 68,1% and 52,2% of patients in in those groups, respectively. We have measured IIEF scours one year after the surgery in all patients with good initial sexual activity. Additionally, we have used one more 5-level questionnaire developed by us to fix the level of subjective patient sexually quality of life satisfaction. Answer «5» means that the patient achieved the same sexual life quality he had before the procedure. Results Sexual rehabilitation (IIEF ≥17) one year after the surgery was registered in 77,1% patients after RARP and 44,4% in RRP group. It looks very remarkable that only 25% of patients from the RRP group marked the level of "subjective sexually quality of life satisfaction” like "4” and nobody like "5” one year after the procedure. In comparison, in RARP group "4” and ”5” marks were given by 54.2% and 4,2% of patients, respectively. (Tab. 1) Conclusions Robotic prostatectomy is associated with a better sexual rehabilitation results one year after the procedure in comparison with RRP. (p 0.05)
PILOT STUDY EVALUATING SAFETY AND FEASIBILITY OF INTRAVESICAL INSTILLATIONS OF BOTULINUM TOXIN IN HYDROGEL-BASED SLOW RELEASE DELIVERY SYSTEM IN BPS/IC PATIENTS
Y. Rappaport1, K. Stav1, Y. Vinshtok2, M. Jeshurun2, N. Ivgy-May2, T. Gerassi2, A. Zisman1
1Department of Urology, Assaf Harofeh Medical Center, Israel
2Theracoat, Theracoat Limited, Israel
Introduction and Objective:Intravesical instillation of botulinum toxin-A (BTX) is an appealing alternative to intradetrusor injection for treating painful bladder syndrome/interstitial cystitis (PBS/IC) but lacks a sustained effect due to a short exposure of urothelium to BTX. TCGel (TheraCoat Ltd) is a novel reverse-thermal gelation hydrogel allowing for instillations of liquid TCGel+BTX mixture into the bladder where it solidifies and BTX gradually releases for 6-8 hours. We investigated the feasibility and safety of intravesical instillation of BTX dissolved in TCGel preparation in patients with PBS/IC. Methods: A single intravesical instillation of 200U onabotulinumtoxin-A premixed with 40ml TCGel through 12Fr urethral catheter was delivered. Adverse events (AEs) and preliminary efficacy outcome measures were: bladder diary, Visual Analogue Scale (VAS), IC symptom and problem index (ICSI, ICPI). They were assessed at 2, 6 and 12 weeks following instillation. Results: 15 (M/F=4/11, age 24-76) severely symptomatic PBS/IC patients (ICSI range 12-19, ICPI range 12-16, median VAS=7) were enrolled. Safety: No increase in VAS score was noted at instillation. One severe AE was reported - an excisional biopsy of pre-existing sub-mandibular lymphadenopathy (benign histology). Three cases of mild constipation 24h to 3 weeks following instillation were noted as possibly drug-related AE`s. Non-related AEs include post-instillation mild urogenital infection, flu and a case of worsening of bladder pain and depression symptoms at Week 12. Possible efficacy: Reduction in ICSI, ICPI and VAS was maintained throughout the follow-up period. Voiding frequency, nocturia and urge decreased up to Week 6 but returned to baseline level at Week12 (figure). Conclusion: The results suggest that intravesical instillation of the novel TCGel+BTX is safe and tolerable. Preliminary results suggest sustained efficacy for weeks. A randomized controlled trial is warranted.
Salivary Neutrophil Gelatinase-Associated Lipocalin (NGAL)and Cortisol measurement in acute Renal Colic
Y.I. Siegel1, A. Tamimi1, E. Kord1, Y. Rappaport1, A. Cooper1, R. Abu Hamad2, S. Efrati3, A. Zisman1
1Urology, Assaf Harofeh, Israel
2Nephrology, Assaf Harofeh, Israel
3Nephrology and Hyperbaric Center, Assaf Harofeh, Israel
BACKGROUND: In acute ureteral stone obstruction the decision to treat is sometimes missing a forecaster for a better outcome. Neutrophil Gelatinase-Associated Lipocalin (NGAL) levels are predictive biomarker of Acute Kidney Injury (AKI) with correlation to complication and survival in major surgery. Cortisol levels in saliva found to be a reliable parameter for stress. OBJECTIVE To measure salivary NGAL and Cortisol levels in patients presented to the Emergency Room (ER) with acute renal colic. METHODS: Prospective controlled study of all patients who presented to ER with acute renal colic and diagnosed with single ureteric stone obstruction by non-contrast computed tomography (NCCT). Saliva, urine and blood samples were collected in patients and control group during the first morning of admission. RESULTS: 27 patients in the study group, 11 in the control group, mean age 48±13 years, BMI 28±6, mean stone size 6±4 mm , mean VAS scored of 7±2 ,mean creatinine levels of 1.4±0.4 mgr/dl ,mean WBC 10,900±3,100 count per field ,CRP 29±55 .14 (52%) of patient underwent urgent intervention. Serum (199±154 vs 83±67 p0.001) and, predominantly Salivary (532±102 vs 340±409 ;p0.001) NGAL levels were significantly elevated in patients with acute renal colic in comparison to controls. Cortisol level on the contrary did not demonstrate any increase during acute phase of renal colic, suggestive a delay response or suppression mechanism. CONCLUSION: Salivary and blood NGAL sampling is feasible during acute phase of renal colic. High levels of salivary NGAL are observed in a single sampling during acute ureteral stone obstruction and may advance clinical decision making. Cortisol levels fail to increased suggestive of some suppression mechanism. Reference Kan, J.-P., Rubnow, D.R., Davis, C.L., Kling, M., Post, R.M., 1988.Salivary cortisol: A practical method for evaluation of adrenal function. Biol. Psychiatry. 23,335-349.
Clinical Markers for Modeling Non-Muscle Invasive Bladder Cancer and Optimized Treatment with Bacillus Calmette-Guerin (BCG)
S. Bunimovich-Mendrazhitsky2, A. Kiselyov1, E. Fridman3, V. Startsev4
1Vice-President, Genea Biocells, USA
2Department of Computer Science and Mathematics, Ariel University, Associate professor, Israel
3Department of Pathology, Sheba medical center, Head of Uro-Pathology Unit, Israel
4Department of oncology, pediatric oncology and beam therapy, Saint-Petersburg's State Pediatric Medical University, Professor, Russia
Intravesical Bacillus Calmette-Guerin (BCG) vaccine is the preferred first line treatment for non-muscle invasive bladder carcinoma (NMIBC) in order to prevent recurrence and progression of cancer. There is ongoing need for the rational selection of i) BCG dose, ii) frequency of BCG administration along with iii) synergistic adjuvant therapy and iv) a reliable set of biochemical markers relevant to tumor response. Objective: To evaluate cellular and molecular markers pertinent to the immunological response triggered by the BCG instillation and respective mathematical models of the treatment. Materials and methods:We conducted a critical evaluation of PubMed/Medline and SciFinder databases covering the period 2010-2015 in order to identify literature related to the BCG treatment of NMIBC. The following keywords and phrases were used: bacillus Calmette-Guerin, BCG, bladder cancer, vaccine, immune response, signaling, biological markers, molecular markers, mathematical models, simulation, macrophage, SNP, polymorphism, epigenetics, miRNAs, predictor, prognosis. Evidence synthesis: These include diverse immune cells, genetic polymorphisms, miRNAs, epigenetics, immunohistochemistry and molecular biology ‘beacons’ as exemplified by cell surface proteins, cytokines, signaling proteins and enzymes. A panel of these parameters in combination with data on patients’ (patho)physiology, tumor stage and aggressiveness are needed to reliably predict both optimized treatment regimen and potential risks. The intricate and patient-specific nature of these data warrants the use of powerful multi-parametral mathematical methods in combination with molecular/cellular biology insight and clinical input. Conclusions: We identified tumor associated macrophages (TAMs), Human Leukocyte Antigen (HLA) Class I, a combination of Ki-67/CK20, IL-2, IL-8 and IL-6/IL-10 ratio as the most promising markers for both pre-BCG and post-BCG treatment suitable for the simulation studies.
V. Startsev1, R. Sen'kov2
1Department of Oncology, Pediatric Oncology and Beam Therapy, St.-Petersburg's State Pediatric Medical University, Professor, Russia
2State Medical Information and Analytical Center, Head of Information-Analytical Department of Medical Care, Russia
Prostate cancer (CaP) ranks high place among socially significant diseases, refers to the neoplasm with dynamically growing temp in Europe and in Russia. We analyzed medical and statistical indicators of CaP in St. Petersburg (SPb) in 2004-2013 based on data from the official registration forms. The absolute number of newly and death CaP cases increased in 51,2% and 24,7%/100 thous., resp., with the peak of incidence in men older 60 y. CaP held 8th ranking place of incidence (5,4%) and 9th – of mortality (4,5%) in SPb (2013). The ratio of dead/diseased CaP (in Europe 85,7%) in SPb was 55,1% and the number of death cases increased by 23,9%, which indicates the need to improve the diagnostic. The number of CaP cases in early stages increased from 4,6 to 11,2/100 thous., similar to situation in Russia. CaP stage IV decreased on 85 pts/year, far ahead from country rates. To assess the premature mortality rate we used the index - the "Lost Years of Potential Life”. The number of CaP pts who lived less than 70 y. (2011-2013), increased in 60-64 y. and in 45-49 y.y.: the elderly and the working-aged men. That greatly helped to evaluate the effect of healthcare measures. We need to improve the quality of statistical monitoring for neoplasm with ICD-10, continue building the knowledge base for urologists, improve the medical care for CaP patients, select clinical trials with new drugs, perform epidemiological studies for prevention of new CaP at the city with significant group of elderly people.
G. Verhovsky1,2, A. Hoffman1, A. Zisman2
1Medical Corps, IDF, Israel
2Urology department, Assaf Harofeh Medical Center, Israel
Objectives: To compare long term results in varicocele treatment in professional soldiers. Methods: Billing documents for varicocele repair surgeries issued by Israeli Defense Forces (IDF) medical corps were evaluated since 1970. The population chosen was of professional soldiers bearing a medical record of varicocele. Fertility was evaluated by live births and time to first child. Results: 4713 professional soldiers bearing a record of varicocele served since 1970. Among them 1845 (35%) were married, 87 were operated (4.7%) and 1758 were observed.63 (72%) were operated before marriage and 24 after (primary infertility). In the operated population due to primary infertility live birth was achieved in 58% in comparison to 79% of soldiers operated before marriage (p=0.047). The rate of live birth in the control group was 76% (p0.0001). No difference was noted in live birth rate between operated and the observation group. In the group that was operated prior to marriage a 3.76 y delay was noted to the birth of first child compared with 1.86-2.03 y in the other groups. Conclusions: The rate of live birth in soldiers with varicocele record is notably lower than the control group. This was corrected among subjects who were operated before marriage as a preventive surgery. Observation led to lower live birth rate than in the control group but without statistical difference from soldiers operated with preventive intent suggesting an adequate patient selection for surgery and observation.
Prenatal diagnosis of fetal urinary tract anomalies leading to termination of pregnancy
G. Verhovsky1, A. Neheman1, G. Kaplan2, R. Maymon2, A. Zisman1
1Department of Urology, Department of urology, Assaf Harofeh Medical Center, affiliated to the Sackler Faculty of Medicine, Tel-Aviv University, Israel
2Department of gynecology, Assaf Harofeh Medical Center, affiliated to the Sackler Faculty of Medicine, Tel-Aviv University, Israel
Objective: To characterize prenatal diagnosis of fetal urinary tract anomalies (UTA) leading to termination of pregnancy (TOP). Methods: TOP records performed between January 1998 to April 2015 where reviewed. Inclusion criteria are TOP due to anatomic or chromosomal anomalies. Cases where stratified to two groups according to concomitant anatomic or chromosomal abnormalities. Results: There were 2535 cases of TOP (55% due to anatomic abnormalities and 45% due to genetic or chromosomal anomalies). UTA were present in 261(10.3%) of all cases of TOP: Group 1: 112 (4.4%) cases with predominantly UTA leading to TOP 96 (3.8%) major UTA in conjunction with additional abnormalities in 16 (0.6 %) cases Group 2 - UTA was not the main reason for TOP - 149 (5.9%) cases The reason for TOP in group 1 were renal agenesis 39%, bladder outlet obstruction 23%, ADPKD 11%, multi-cystic dysplastic kidney 11%, bladder agenesis 6.2%, bilateral severe hydronephrosis 3.6 %, cloacal malformation 2.7 %, bladder exstrophy 1.8% , bilateral hyperecogenic kidneys 1.8%. In the group with predominant UTA, 99 (88%) cases where diagnosed with an abnormality considered incompatible with life. Conclusions: UTA is diagnosed in 10% of TOP and is the predominant reason in 4%. Common findings are renal agenesis and bladder outlet obstruction. 88% of UTA are considered severe and only 12% may potentially have reasonable prognosis.
G. Verhovsky1, A. Neheman1, G. Kaplan2, R. Maymon2, A. Zisman1
1Urology Department, Assaf Harofeh Medical Center, Israel
2Obstetrics and Gynecology, Assaf Harofeh Medical Center, Israel
PURPOSE: To evaluate the association between trisomy 21 and prenatal hydronephrosis at second trimester ultrasonography in fetuses with trisomy 21. METHODS: Retrospective cross-sectional assessment of fetus with trisomy 21 diagnosed by fetal karyotype obtained by amniocentesis/cordocentesis, between January 1998 and April 2014. Urinary tract abnormalities (UTA) where characterized according to morphological ultrasonography findings. Fetus with isolated UTA were compared to those with multiple systemic anomalies including UTA. RESULTS: There were540 cases of trisomey 21. Isolated UTA in 13 cases (2.4%) and 21 cases (3.9%) with multiple fetal abnormalities. Overall UTA was recognized in 34 cases (6.3%). The main anomaly in both groups was bilateral mild pelviectasis (less than 5 mm.) and one case of posterior urethral valve. Only in the isolated UTA there was one case (2.9%) that both nuchal screening and triple test (1:470) where considered normal and trisomy 21 was primarily diagnosed by amniocentesis. In the rest of the trisomy 21 population without UTA (n=506) there were 11such cases (2.2%, p0.05). CONCLUSION: Prenatal diagnosis of UTA is known to be increased in fetus with trisomy 21 and is considered to be a "soft marker". Our data suggest that although the most common finding is bilateral pelviectasis, UTA do not perform as a fair marker for un diagnosed trisomy 21.
SYSTEMIC ENDOTHELIAL FUNCTION MEASURED BY FLOW-MEDIATED DILATION IS IMPAIRED IN PATIENTS WITH UROLITHIASIS
E. Yencilek1, H. Sarı2, F. Yencilek3, H.H. Koyuncu3, H. Aydın4
1Department of Radiology, Haydarpasa Numune Education and Research Hospital, Turkey
2Department of Internal Medicine, Bagcilar Education and Research Hospital, Turkey
3Department of Urology, Yeditepe University Medical Faculty, Turkey
4Departmet of Internal Medicine, Section of Endocriology and Metabolism, Yeditepe University Medical Faculty, Turkey
Aim There are studies reporting increased risk of cardiovascular diseases (CVD) in urolithiasis. Endothelial dysfunction is the early key element for the development of CVDs. Some in vitro and animal studies have shown endothelial dysfunction in hyperoxaluria models. The aim of this study is to investigate endothelial function in patients with urolithiasis in relation to urinary stone risk factors and metabolic parameters. MethodsA total of 100 subjects without any known CVD (60 with urolithiasis and 40 healthy subjects) were included into the study. Fasting blood samples were obtained to study metabolic parameters (glucose, lipids). Urine stone risk factors (oxalate, citrate, uric acid, calcium, pH) were studied in 24-hour urine samples. Endothelial function was assessed as flow-mediated dilation (FMD) at the brachial artery. Results Age, sex and body mass index were similar in patients and controls. Fasting blood glucose, total and LDL-cholesterol and triglyceride were higher and HDL-cholesterol was lower in patients than controls. Although within normal limits systolic blood pressure was higher in patient group. Of urine stone risk factors, oxalate and citrate were higher in patients than controls. Patients with urolithiasis had a lower %FMD than controls. Urinary oxalate excretion was positively correlated with age (p0,001, r=0,442), BMI (p0,001, r=0,562), total cholesterol (p0,001, r=0,571) and negatively with %FMD (p0,001, r=-0,527). Age (p0,001, r=0,694), BMI (p0,001, r=0,389) and total cholesterol (p0,001, r=0,559) were also negatively correlated with %FMD. Conclusions This is the first study demonstrating endothelial dysfunction in human subjects with urolithiasis. This indicates a possible predictive role of urolithiasis in future development of cardiovascular diseases.
F. Yencilek1, H. Aydın2, J. Coban3, H.H. Koyuncu1, H. Sarı4, Y. Bastug5, S.Turkan6
1Department of Urology, Yeditepe University Medical Faculty, Turkey
2Endocrinology and Metabolism Department, Yeditepe University Medical Faculty, Turkey
3Department of Biochemistry, Yeditepe University Medical Faculty, Turkey
4Department of Internal Medicine, Bağcılar Education and Research Hospital, Turkey
5Department of Urology, Fatih Sultan Mehmet Education and Research Hospital, Turkey
6Department of Urology, Kastamonu Anadolu Hospital, Turkey
Aim: Renal tubular injury is an essential component of renal stone disease. Several mechanisms were proposed to explain how renal tubular injury occurs. But the exact mechanism is still obscure. Oxidative stress is closely related in pathogenesis and oxidative damage to DNA is one of the mechanisms of cellular injury. Although increase in oxidative DNA damage markers was reported in urolithiasis, none of them are conclusive on the direct effect of calcium oxalate crystals. The aim of this study was to investigate whether oxidative DNA damage and renal tubular cell apoptosis makers can be induced by hyperoxaluria in an animal model study. Materials and Methods: A total of 16 Sprague Dowley rats have been included into study. Group I (n=8): Hyperoxaluria-induced group; Group II (n=8): Control group. Twenty four hour urine samples were collected at 24 hour, 14 day and 28 day after hyperoxaluric diet for the analysis of 8-hydroxydeoxyguanosine (8-OHG) and oxalate excretion. Rats were euthanized at 28th day and right kidney was taken for immunohistochemical analysis for apoptosis markers Fas/Fas-ligand, TNF-α/TNFR1.
Results: Compared to controls, 8-OHdG excretion was found to be higher in hyperoxaluric group (p0,05). It began to rise early at 24-hour samples and stayed high throughout 28-day period. It was positively correlated with urinary oxalate excretion (p=0,03, r=0,53) and renal tubular epithelial cell apoptosis markers (p=0,007, r=0,710).
Conclusions: Results indicate hyperoxaluria induced oxidative damage to DNA mediates renal tubular injury. This may contribute to the pathophysiology of renal stone disease and help to explain its relationship with other systemic diseases.