Abstracts 1

Clinical Oral Presentation COP-01 High R.E.N.A.L nephrometry scores (RNS) are associated with pathological upstaging of clinical T1 renal cell carcinomas (RCC) in radical nephrectomy (RN) specimens: implications for nephron-sparing surgery

M.H.W. TAY*, T.P. THAMBOO§, F.M.W. WU*, Z.J. CHEN†, B.C. TAI‡, R. LATA* and H.Y. TIONG* *Department of Urology, National University Health System, Singapore; †Investigational Medicine Unit, National University Health System, Singapore; ‡Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore; §Department of Pathology, National University Health System, Singapore

Introduction: The R.E.N.A.L Nephrometry Score (RNS) was developed to standardise the reporting of anatomical information of a renal mass. This study aimed to identify the association of preoperative clinical and tumor features assessed by the RNS with pathological upstaging of clinical T1 renal cell carcinomas (RCCs) in complete en bloc radical nephrectomy (RN) specimens. Materials and Methods: A review was performed for 65 consecutive RN patients (2005–2013), performed for a unilateral clinical T1N0M0 RCC. The RNS was measured in all patients based on preoperative computer-tomographic scans. Pathological review was performed to identify patients with final pathological upstaging. Associations were assessed with Fisher’s exact test, student t test and Wilcoxon rank-sum test. Results: Of the 65 patients (41 male, mean age 59 years), 4 (6%) patients were upstaged to pT2 and 16 (25%) were upstaged to pT3a and above in the final histology. Upstaged patients were not significantly different from those without in terms of age, gender, race, surgical approach, side, grade and cell type. Independent tumor features associated with pathological upstaging were (R) tumor diameter (p = 0.021), and (L) central location within polar lines (p = 0.010). Tumors which were upstaged had a higher median total RNS than those without (9

vs. 10, p = 0.010). Complex tumors, with RNS ≥10, were associated with significantly increased risk of upstaging compared with low and intermediate complexity categories (RNS < 10) (RR = 2.56, 95% CI 1.22–5.37, p = 0.014). Conclusions: A higher RNS was associated with an increased risk of upstaging in clinical T1 cancers, predominantly from perinephric or sinus fat invasion in RN pathological specimens. This may have implications on the selection of surgical option for the clinical T1 renal mass. COP-02 Long term results of a double-blind randomised controlled trial of interferon alpha-2b and low dose BCG in patients with high risk nonmuscle-invasive bladder cancer K. ESUVARANATHAN*,†, S.M. THAM*, M. RAVURU*, R. KAMARAJ*, T.P. NG‡, Y.H. CHAN§, C.W.S. CHENG¶, S.J. CHIAk, F.C. NG**, L. FENG‡ and R. MAHENDRAN* *Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; †Department of Urology, National University Health System, Singapore; ‡ Department of Psychological Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; §Dean’s Office, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; ¶ Department of Urology, Singapore General Hospital, Singapore; kDepartment of Urology, Tan Tock Seng Hospital, Singapore; **Department of Urology, Changi General Hospital, Singapore

Introduction: Bacillus Calmette-Guerin (BCG) immunotherapy, at full-dose in a maintenance schedule of 36 months, reduces recurrence and progression of high risk non-muscle-invasive bladder cancer (NMIBC). However, many patients do not complete the full course due to its toxicity or non-compliance. We report long-term results of a trial to evaluate the efficacy and toxicity of reduced dose Connaught-strain BCG with interferon alpha-2b (IFNa-2b). Material and Methods: This was a prospective, randomised, double–blinded, controlled, multi-institution clinical trial in which 140 patients with Stage Ta or T1 bladder cancer and/or CIS were assigned to one of three therapies following transurethral resection. Patients received 6weekly intravesical instillations of full-dose BCG (81 mg) or low-dose BCG (27 mg)

© 2014 The Authors. BJU International © 2014 BJU International | 113, Supplement 3, 1--37

or low-dose BCG plus IFNa-2b (10 MU) followed by 3 weekly booster instillations 6 weeks after the 6th instillation. They underwent close surveillance with regular cystoscopy and urine cytology. End points were time to local recurrence, recurrencefree probability and mortality. Results: Both local and systemic symptoms were significantly decreased in the low-dose combination arm compared to full-dose BCG during the first 6 instillations but not for the booster instillations. The evaluable study cohort (n = 108) was followed up to 207 months, with a total of 35 recurrences and 56 deaths. Five years after randomisation, the probability of being recurrence-free were 56.4% and 78.2% in the full-dose BCG and combination arms respectively (p = 0.037). The mean time to recurrence was 118 months for full-dose BCG compared to 145 months for the combination arm. Conclusions: Reducing the dose of BCG decreased its toxicity during the induction course while efficacy was increased by combining it with IFNa-2b. A short course of “6 + 3” combined therapy using reduced dose BCG may be sufficient to achieve similar results to longer term, fulldose BCG therapy. This finding is significant as it provides an alternative therapy for high risk NMIBC patients. COP-03 Comparison of pathological upgrading and upstaging of patients with low-risk prostate cancer suitable for active surveillance according to currently used clinical guidelines D.Z. YONG, T.W. TAN, S.J. CHIA and K.T. CHONG Department of Urology, Tan Tock Seng Hospital, Singapore

Introduction: We aim to compare the pathological upgrading and upstaging rates between patients with prostate cancer who met the criteria for active surveillance based on the National Comprehensive Cancer Network (NCCN) or European Association of Urology (EAU) or Singapore Urological Association (SUA) clinical practice guidelines, but were treated with radical prostatectomy. Material and Methods: 317 men were treated with radical prostatectomy at Tan


2 Abstracts

Tock Seng Hospital from August 2000 to October 2013. 73 patients met the NCCN criteria for active surveillance: (1) cT1 to cT2a, (2) prostate-specific antigen (PSA) less than 10 ng/ml, and (3) biopsy Gleason sum 2 to 6. 35 met the EAU guidelines, which had additional criteria of: (1) 2 or less biopsy cores positive, and (2) 50% or less Ca detected per core. 25 of these men met the SUA guidelines, which additionally required a prostatespecific antigen density (PSAD) of 1 pad/day. There were no cancer related mortalities. Conclusion: RARP can achieve good disease control in selected HR PCa patients, and allow time off initial androgen deprivation therapy. A prolonged follow-up is needed to ascertain long term oncological efficacy.

Introduction: Robotic assisted Radical Prostatectomy (RARP) is widely accepted as part of a multimodality treatment for © 2014 The Authors. BJU International © 2014 BJU International | 113, Supplement 3, 1--37

Abstracts 3

COP-06 The oncological outcomes of robotic assisted radical prostatectomy in an unscreened multi-racial Asian population A.W.X. LOW, H.G. SIM, H.S.S. HO, C.W.S. CHENG and L.S. LEE Department of Urology, Singapore General Hospital, Singapore

Introduction: There are few publications focused on robotic assisted radical prostatectomy (RARP) in unscreened multiracial Asian populations. This study evaluates the surgical and oncological outcomes following RARP in such a patient population from a single institution. Materials and Methods: All patients who underwent RARP between 1st January 2003 and 30th June 2013 were identified from a prospectively maintained cancer registry. Those with follow-up durations less than 6 months and non-adenocarcinoma histology were excluded. The parameters analysed include demographic factors, peri-operative, pathological and oncological outcomes. The rate of biochemical recurrence and need for adjuvant therapy were also reviewed. Results: There were n = 725 suitable patients with a mean age and follow-up duration of 62 years and 2 years respectively. There were 79% (n = 571/725) Chinese, 2% (n = 16/725) Malays, 3% (n = 24/725) Indians and 16% (n = 115/ 725) other ethnicities. The mean operative time, EBL and LOS were 186 minutes, 215 ml and 3 days respectively. Post-operatively, 79% (n = 569/725) of patients had no complications and 18% (n = 128/725) had minor (Clavien grade I-II) complications. The pathological stage was pT2 in 68% (n = 497/725), pT3 in 32% (n = 227/ 725) and n = 1 patient with pT4 disease. There were 28% (n = 202/725) with pathological Gleason score 6 or less, 63% (n = 461/726) with Gleason 7 and 8% (n = 58/726) with Gleason scores 8 and above. Of the n = 361 patients who underwent pelvic lymphadenectomy, 6% (n = 21/361) were node positive. The positive surgical margin rates were 31% (n = 154/497) and 71% (n = 161/227) for pT2 and pT3 respectively. The biochemical recurrence (BCR) rates were 10% (n = 51/ 497) and 23% (n = 53/227) for pT2 and pT3 respectively. Of those with BCR, 57% (n = 59/104) underwent adjuvant therapy, comprising irradiation for 90% (n = 53/

59) and androgen deprivation for 10% (n = 6/59) respectively. Conclusion: Despite a higher incidence of advanced stage disease in this population, RARP remains safe and oncologically feasible, especially in an institution with intermediate level workload. COP-07 A treatment journey of 108 men on active surveillance for prostate cancer: why men change? K.J. TAY, H.H. HUANG, L.S. LEE, C.W.S. CHENG and J.S.P. YUEN Department of Urology, Singapore General Hospital, Singapore

Introduction: Patients with very low-risk prostate cancer (vLR-PCa) were deemed to be good candidate for active surveillance (AS). Analysing the treatment journey of these men on AS, in particular evaluating the reasons for discontinuing AS in favour of active treatment is the main objective of this study. Materials and Methods: The Singapore General Hospital Urology cancer database was queried for men diagnosed with vLRPCa, using Epstein criteria (Gleason score ≤6, single-core ≤50% or ≤3 cores ≤30% core-length involvement, PSA≤10, clinical stage ≤ T2a) from 2002–2013. Records were reviewed to determine the natural history of these men’s prostate cancer and the indications for intervention. Results: 108 of 366 patients (29.5%) diagnosed with vLR-PCa elected for active surveillance. The median follow-up was 33.8 (range 2.0–117.7) months with the median period of surveillance 20.8 (range 2.0– 105.6) months. Sixty patients (55.6%) were monitored using PSA only, 48 received at least 1 re-biopsy and 1 received 2. PSA doubling-time was calculable in 44 patients and was >3 years for all of them. Two patients (1.85%) died, both of noncancer related causes. Seventy patients (64.8%) remained treatment-free, and 38 patients (35.2%) underwent radical intervention. Eighteen patients (16.7%) underwent radical prostatectomy, 13 (12%) radiation and 7 high-intensity focused ultrasound. One patient had biochemical recurrence after prostatectomy and had salvage radiation. The reason for intervention among the 38 patients was rising PSA (n = 9, 38%), upgrading (n = 7, 18%), upstaging (n = 6, 16%) and patient’s choice despite stable disease (n = 16,

© 2014 The Authors. BJU International © 2014 BJU International | 113, Supplement 3, 1--37

42%). Those choosing intervention despite stable disease had a shorter period of surveillance compared to the rest (10.0 vs. 22.5 months, p = 0.004). Conclusions: Active surveillance is accepted by a third our local population for very low-risk prostate cancer with 65% of these remaining treatment-free at 33 months. Only 14.8% of patients chose intervention despite stable disease. COP-08 Determining the effects of radical prostatectomy on penile length by comparing objective surgical parameters of 45,536 patients who underwent penile prostheses insertions

K.C.J. LEE*, L.DE YOUNG† and G.B. BROCK† *Department of Urology, National University Hospital, Singapore; †Division of Urology, St Joseph’s Health Care, London, ON, Canada

Introduction: Penile shortening has often been reported as a common sequelae of radical prostatectomy. Denervation and vascular compromise during surgery are thought to cause significant corporal fibrosis resulting in penile shortening. The degree of penile length loss reported in literature to date, been based on subjective measurements such as stretched penile length and patient self-reporting. We believe objective measurements are essential to allow urologists to quantify the actual loss of penile length expected after radical prostatectomy and counsel patients. Materials and Methods: A retrospective review of the American Medical System (AMS) PIF Database was done to study the surgical parameters of patients who have undergone penile implants in US and Canada between 2002 and 2011. Patients with Peyronie’s disease, genital trauma and other conditions known to affect penile lengths were excluded. Patients with prostatectomy, diabetes, vascular disease and organic erectile dysfunction (ED) were included. Results: A total of 45,536 patients were included in the study, with 14,507 patients in the Prostatectomy Group and 31,029 patients in the Non-Prostatectomy group. The mean age of Prostatectomy patients is 64.0 years and 62.4 years in the Non-prostatectomy group (p < 0.001). The majority of patients in both groups had an AMS 700 inflatable penile prosthesis inserted (Prostatectomy 82.5%, Non-prostatectomy 3

4 Abstracts

76.9%) using a penoscrotal approach (Prostatectomy 69.4%, Non-prostatectomy 66.8%, p = 0.185). The mean total corporal measurement is 19.4  2.2 cm in the Prostatectomy group and 19.7  2.2 cm in the Non-prostatectomy group (p < 0.001). This 0.3 cm difference is consistently seen in the mean total length of implant components used, which is 19.1  2.3 cm in the Prostatectomy group and 19.4  2.4 cm in the Non-prostatectomy group (p < 0.001). Conclusions: Based on actual surgical measurements, the average penile length of post-prostatectomy patients who underwent a penile implant is 0.3 cm shorter than non-prostatectomy patients. Although statistically significant, this degree of difference, which is attributed to radical prostatectomy, is unlikely to impact overall sexual function and in our opinion is not clinically significant. COP-09 A non-inferiority trial comparing the combination of etoricoxib and diclofenac against pethidine as analgesia during extracorporeal shockwave lithotripsy C.F. SHUM, A. MUKHERJEE, C.H. ONG, T.P. LIM and C.P.C. TEO Department of Urology, Khoo Teck Puat Hospital, Singapore

Introduction: Opiates are commonly used as analgesia during extracorporeal shockwave lithotripsy (ESWL). They have good analgesic efficacy and rapid onset of action; but are often associated with significant adverse effects like nausea, respiratory depression and hypotension. Nonsteroidal anti-inflammatory drugs (NSAIDs) are alternatives without the adverse effects of opiates, but their analgesic effect and onset of action seem inferior to opiates. By combining etoricoxib with diclofenac, we aim to spare the use of opiates and yet provide equivalent analgesia throughout ESWL. Materials and Methods: A test of noninferiority was conducted. Patients with renal or ureteric stones undergoing ESWL would be randomised into 2 groups. Group A would receive oral etoricoxib 120 mg at 2 hours and intramuscular diclofenac 75 mg immediately before ESWL. Group B would receive intravenous pethidine 50 mg with metoclopramide 10 mg immediately before ESWL. All ESWLs 4

were performed with a Siemens Modularis Variostar electromagnetic lithotripter following a standard treatment protocol. At the end of ESWL, all patients would rate pain severity using a visual analogue scale from 0 (no pain) to 10 (worst pain). Power analysis (1 – b = 0.80; a = 0.025) determined the minimum sample sise to be 284 patients, at a non-inferiority margin of 1. Besides the severity of pain, any drug-related adverse effects and unexpected interruption to ESWL were also recorded and compared between the groups. Results: A total of 372 patients were randomised into 2 equal groups over a period of 3 years. The following table shows the patients’ demographics, stone characteristics and ESWL details of the 2 groups. The next table shows the end-points of the study. There were no unexpected interruptions to ESWL due to other causes. There were no NSAID-related adverse effects in Group A. There were no other

opiate-related adverse effects besides nausea and vomiting in Group B. Results showed that non-inferiority was claimed, t(370) = 4.17, p < 0.001. The lower bound of the confidence limit was 0.39, which was within the non-inferiority margin. Conclusions: The combination of etoricoxib and diclofenac is not inferior to pethidine as analgesia during ESWL, and is not associated with any adverse effects.

Age (years) Gender (% male) Ethnicity Chinese Malay Indian Others Body mass index (kg/m2) Number of stones Location of stones Kidney Upper ureter Mid-ureter Lower ureter Sise of stones (mm2) Radio-opacity of stones (% radio-opaque) Number of shocks Maximum energy level Average energy level

Pain severity Unexpected interruption to ESWL due to severe pain Nausea / vomiting

Group A

Group B

49.7  12.4 79.0

49.4  12.8 67.7

123 44 15 4 26.8  4.7 1.6  1.6

123 32 23 8 25.9  4.0 1.6  1.9

110 67 2 7 125.3  111.6 96.2 2636.0  898.2 3.2  0.6 2.5  0.6

112 66 3 5 110.2  99.0 95.7 2512.0  891.4 3.0  0.6 2.3  0.6

Group A

Group B

4.7  2.6 6 0

4.5  2.7 6 21

© 2014 The Authors. BJU International © 2014 BJU International | 113, Supplement 3, 1--37

Abstracts 5

Translational Oral Presentation TOP-01 Resveratrol suppresses innate immune responses following TransRectal UltraSound guided (TRUS) biopsy of the prostate

T.W. CHONG*, F.Y. GOH*, J.Y. TA† and S.C. WONG‡ *Department of Urology,Singapore General Hospital, Singapore; †Singapore Immunology Network, Research Officer, Singapore; ‡ Singapore Immunology Network, Principal Investigator, Singapore

Introduction: TRUS biopsy of the prostate is a common urological procedure which worldwide entails about a 5% risk of developing sepsis/septic shock post biopsy. The pathophysiology behind this Systemic Inflammatory Response Syndrome (SIRS) includes the systemic release of pro-inflammatory cytokines. Resveratrol is a natural polyphenol that has been extensively studied as an anti-inflammatory agent. We hypothesise that Resveratrol will have anti-inflammatory effect following TRUS biopsy. The objectives are to examine the effects of Resveratrol on CD14-sorted monocytes from peripheral blood mononuclear cells (PBMC) from patients undergoing TRUS biopsy; and to investigate the effects when given prior to lipopolysaccharide (LPS) stimulation. Material and Methods: IRB approval for the study was obtained. Five patients undergoing TRUS biopsy were initially recruited into the study. PBMC from venous blood taken before and 24 hours after TRUS biopsy were obtained via ficoll separation. CD14+ monocytes were further isolated via magnetic bead sorting and used in the following ELISA (R&D systems) based experiments to measure cytokine expression (TNF-a, IL-1b, IL-6, IL8). Fresh monocytes were plated in wells (3 9 105/well) and variously exposed to LPS (100 ng/ml) and Resveratrol (20 and 40 lM). Experiments were performed in triplicate. Supernatants were collected and frozen for subsequent analyses by batches. Cytokine levels were expressed as mean (pg/ml). Results: CD14+ monocytes from patients prior to TRUS biopsy responded to LPS stimulation in vitro with increased expression of all cytokines studied (TNF-a, IL1b, IL-6, and IL-8). When incubated with

Resveratrol prior to LPS stimulation, there was a decrease in cytokine response. Monocytes taken from patients 24 hours after TRUS biopsy showed increased expression of cytokines versus baseline (prior to biopsy), with a dose-response decrease in expression when incubated with Resveratrol in vitro. Conclusions: The data suggests that Resveratrol reduces the inflammatory cytokine response in CD14+ monocytes to LPS in vitro, and also following TRUS biopsy exvivo. Based on this we further hypothesise that Resveratrol may reduce the systemic inflammatory response in patients post TRUS biopsy. More interestingly, Resveratrol given prophylactically to patients prior to biopsy may reduce the risk of subsequent SIRS. TOP-02 CTLA4 Single Nucleotide Polymorphisms correlate with response to BCG immunotherapy

Y.K. LIM†, R. MAHENDRAN†, S.M. THAM†, J.N. RAHMAT†, J.H. SNG†, L.N. RAMAN*, Z.M.W. MA*, W.C. TSANG*, E. CHIONG*,†, Y.H. CHAN† and K. ESUVARANATHAN*,† *Department of Urology, National University Health System, Singapore; †Department of Surgery, National University of Singapore, Singapore

Introduction: Though BCG is the gold standard for NMIBC, there is a significant non responder rate. The reasons for this are not known though single nucleotide polymorphisms (SNPs) in some genes correlate with response to therapy. Bladder cancer patients who were treated with anti-CTLA4 antibodies had increased CD4+ICOShi IFNc expressing T cells over Treg cell numbers in the bladder and peripheral blood. Therefore seven SNPs in the CTLA4 gene (Rs733618, Rs4553808, Rs5742909, Rs231775, Rs3087243, Rs7565213, Rs960792) that regulate protein expression and function were chosen for analysis. Methods: IRB approval was obtained for this project. SNPs in n = 138 bladder cancer patients, who had previously been treated with BCG and for whom long term follow-up data was available, and n = 146 healthy controls were analysed. Genomic DNA was extracted and subjected to PCR followed by High Resolution Melt (HRM) analysis and sequence analyses. Results: There were no difference in the incidence of SNPs between healthy con-

© 2014 The Authors. BJU International © 2014 BJU International | 113, Supplement 3, 1--37

trols and patients. By Kaplan Meier analysis, GA at Rs4553808 (148 months) and CT at Rs5742909 (167 months) correlated with longer time to recurrence. By COX regression analysis, CT at Rs5742909; AA at Rs3087243; AA and AG Rs7565213 and TT at Rs960792 were significantly correlated with reduced risk of recurrence (p < 0.05). While GA at Rs3087243 and TT at Rs7565213 correlated with a reduced risk of progression (p < 0.05); GA at Rs231775 correlated with an increased risk of progression (p < 0.05, HR 39.4, 95% CI 1.97–795.84). Increased survival was observed in patients with CT at Rs5742909 (p < 0.05). Conclusion: Rs231775 GG is associated with significantly higher T cell activation. Here, Rs231775 GA was associated with an increased risk of disease progression but not AA which is expressed at a lower level in our population. These results indicate that CTLA4 blockade may be a beneficial co-therapy for some bladder cancer patients. TOP-03 Novel urinary biomarkers in bladder cancer

V.H.L. GAN*, J.P. THIERY† and T.W. CHONG* *Department of Urology, Singapore General Hospital, Singapore; †Institute of Molecular and Cell Biology (IMCB-A*STAR), Singapore

Introduction: Urinary biomarkers have potential applications as a non-invasive diagnostic tool for patients suspected of bladder or upper tract urothelial cancer, as well for surveillance for patients who have already been treated for urothelial cancer. Although there are a handful of commercially available assays (e.g. bladder tumour antigen (BTA) assays, NMP 22, Imunocyt, UroVysion), none have sufficient sensitivity and specificity; or are impractical for routine clinical use.Our aim is to identify highly sensitive/specific urinary biomarkers with the potential for development into a non-invasive, point-of-care device with minimal turnover time which would be cheap and easy to use. These biomarkers would ideally be not only diagnostic for new and recurrent tumours, but prognostic for high grade tumours and predictive for response to intravesical chemotherapy/ immunotherapy. Materials and Methods: This is a prospective study involving patients from Singapore General Hospital. CIRB approval 5

6 Abstracts

was obtained. Voided urine samples from patients undergoing surgery for bladder cancer (subjects) and extracorporeal shockwave lithotripsy (ESWL) for urinary stone disease (controls) were collected, stored and analysed in batches. The first step was to identify candidate protein biomarkers using mass spectrometry. Next, validation of these identified candidate biomarkers were performed using RT-PCR, Western blot, immunohistochemistry and quantified using dot blot and ELISA. Comparison of these biomarkers was performed between the 3 groups, i.e. controls, patients with superficial bladder cancer, and patients with invasive bladder cancer. The receiver operating characteristic (ROC) curve for each identified biomarker was derived and area under curve (AUC), sensitivity, specificity, positive and negative predictive values (PPV & NPV) were determined. Accuracy analysis was also performed for combinations of these biomarkers. These were compared to results for Complement H, a FDA-approved bladder cancer biomarker. Results: Five potential biomarkers were identified. The AUC for ROC curves of these makers ranged from 0.66–1.0 for Ta/ T1 bladder cancer patients and 0.78–1.0 for T2/T3 patients. Sensitivity ranged between 60–100% and specificity ranged from 80–100% for each biomarker. The overall accuracy of each biomarker was between 66.7–100%, with higher accuracy obtained in patients with invasive bladder cancer. Conclusion: We have identified 5 promising biomarkers for bladder cancer. These have demonstrated potentially higher accuracy in identifying bladder cancer than current commercially available urinary biomarkers. The next step in our study is to validate these biomarkers in a larger cohort of patients with the aim to develop a point-of-care device.


TOP-04 Optimisation of orthotopic bladder tumor implantation in a syngeneic mouse model C. TAN*, S.M. THAM*, A. RAMASAMY*, E. CHIONG*, K. ESUVARANATHAN*,† and R. MAHENDRAN* *Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; †Department of Urology, National University Health System, Singapore

Introduction: The orthotopic model is a powerful tool to understand and develop better treatments for human diseases. This study was conducted to improve our existing mouse model of bladder cancer. The aims are (1) to evaluate methods of tumor implantation, (2) to assess ways to monitor tumor growth and (3) to investigate the effect of anesthetic drugs on mice. Material and Methods: C57BL/6 female mice were implanted with MB49-PSA, a murine bladder tumor cell-line secreting prostate specific antigen (PSA). The 2 methods of tumor implantation were (1) instillation with poly-L-lysine (PLL) or (2) damage to the bladder wall using an electrocautery device; followed by the instillation of tumor cells. Tumors were monitored using either high frequency ultrasound scan or fluorescence emitted by labeled tumor cells and urinary PSA. Mice were anesthetised with either inhalational isoflurane or an injectable cocktail of medetomidine, midazolam and fentanyl and reversed by atipamezole and flumisenil. Mice were anesthetised and monitored twice weekly for a duration of 1 month after which bladders were harvested for PSA gene expression. Results: Both anesthesia used were well tolerated, even as the mice become weakened by the tumor load. Tumor implantation was confirmed by PSA in the urine. However, urinary output decreased when the tumor grew larger. Tracking fluorescent tumor cells was unreliable due to high background of C57BL/6 mice. Ultrasound scanning of the bladder tumor did allow the tracking of tumor growth in vivo. Conclusions: The injectable cocktail was a safe alternative to the inhalation anesthetic. It was tolerated after repeated twice weekly administration. Ultrasound is a good alternative to monitor tumor sise when urine cannot be collected or if there is hematuria.

TOP-05 Role of NFjB signaling pathway in the molecular mechanism of action of YM155 in renal cell carcinoma (RCC) M.Y. SIM*, M.L. GO† and J.S.P. YUEN* *Department of Urology, Singapore General Hospital, Singapore; †Department of Pharmacy, National University of Singapore, Singapore

Introduction: The deregulation of the NFjB signaling cascade has been associated with human cancers including RCC, where it is constitutively activated. YM155 is a known survivin inhibitor that possesses potent anti-proliferative activity. The objective of this study is to investigate the role of NFjB signaling pathway in the molecular mechanism of action of YM155 in RCC. Materials and Methods: Paired isogenic human RCC cell lines: 786.0 EV and 786.0 VHL (VHL-mutant and VHL-wt), RCC786.0, primary RCC cell lines (NCC010, NCC035, P.RCC), and a human non-malignant cell line (IMR90) were used in this study. MTS cell proliferation assay was used to determine IC50 of YM155 on these cell lines. The binding activity of nuclear p65 was determined using a chemiluminescent-based NFjB p65 transcription factor kit. The transcription activity of NFjB in YM155 treated and untreated RCC786.0 cells was determined using a luciferase reporter assay. Quantitative real-time pcr and western immunoblotting were performed to determine the expression levels of molecules associated with the NFjB signaling pathway. Results: YM155 demonstrated potent nanomolar growth inhibitory activity, compared to known NFjB inhibitor on various RCC cell lines. In addition to survivin inhibition, it reduced nuclear translocation of NFjB in RCC786.0 in a dose dependent manner. YM155 significantly inhibits the TNFa-induced transcriptional activity of NFjB in RCC786.0. YM155 upregulated the expression level of cyld in NFjB signaling pathway. Conclusion: Our data suggests that the anti-survivin agent YM155 inhibits other oncogenic targets such as NFjB at concentrations that are closely aligned to its growth inhibitory IC50. Inhibition of both NFjB and survivin by YM155 leads to profound growth inhibition of RCC cells, suggesting a potential candidate drug for clinical development.

© 2014 The Authors. BJU International © 2014 BJU International | 113, Supplement 3, 1--37

Abstracts 7

TOP-06 Association of natural resistanceassociated macrophage protein 1 (NRAMP1) polymorphisms with response to BCG immunotherapy for non-muscle invasive bladder cancer

Z.T. WANG*, J.H. SNG†, R. MAHENDRAN†, Y.K. LIM†, L. RAMAN NEE MANI* and E. CHIONG*,† *Department of Urology, National University Health System, Singapore; †Department of Surgery, National University of Singapore, Singapore

Introduction: Intravesical administration of Bacillus Calmette-Guerin (BCG) is the current standard of care for non-muscle invasive bladder cancer (NMIBC). However, response is variable, with a 60% success rate and 5 year recurrence rate of 30– 40%. Its mechanism of action involves the generation of tumoricidal macrophages, and the induction of inflammatory cytokines. The NRAMP1 gene is postulated to modulate the induction of macrophage functions. We aim to investigate the role of polymorphisms of this gene in the therapeutic efficacy of BCG. Materials and Methods: We evaluated 139 patients with NMIBC who had received a “6 + 3” regime of intravesical BCG instillations from 1995 to 2013. Genomic DNA was extracted from peripheral blood of patients and controls using the QIAamp blood kit. Three NRAMP1 polymorphic loci, rs17235409, rs17235416 and rs1059823, were genotyped using high resolution melt (HRM) analysis. Fisher’s test and multivariate analysis was performed. Results: Fifty four (38.8%) patients experienced recurrences. Median follow-up was 180 months (13–207). Overall mean time to recurrence was 127 months (95% CI111–114) and mean progression time was 179 months (95%, CI125–154). Genomic frequencies were similar between NMIBC and controls. Age at diagnosis was significantly associated with recurrence (HR 1.05, p = 0.008), progression (HR = 1.1, p = 0.015) and overall survival (HR = 1.1, p < 0.001) in the multivariate analysis. There was no significant association between the polymorphisms studied and recurrence rates. However, in patients who recurred, lower frequency of rs1059823 A:G genotype was seen (OR = 0.66, p = 0.225) which may suggest a trend towards protective effect.

Conclusion: We previously found that certain genetic polymorphisms of NRAMP1 may be associated with susceptibility to recurrences. However, our present results suggest that not all NRMAP1 polymorphisms are associated with patient outcome. Further study with larger sample sise is needed. TOP-07 A brief in vitro activation is sufficient to equip naturally-occurring regulatory T Cells to control allograft rejection long-term

T. CHAN*,†, K.J. WOOD† and A.R. BUSHELL† *Department of Urology, Singapore General Hospital, Singapore; †Nuffield Department of Surgical Sciences, University of Oxford, UK

Introduction: Regulatory T cells (Treg) have been well recognised as potential therapeutic agents in transplantation in recent years. However, the question regarding Treg population selection has remained unanswered. Our previous data suggested that neither freshly-isolated, nor polyclonal expanded naturally-occurring regulatory T cells (nTreg) could effectively prevent allograft rejection in vivo. On the other hand, circumstantial evidence has shown that Treg require activation in order to mediate their function, both in vitro and in vivo. In this study, we demonstrated that a brief polyclonal activation using anti-CD3 and anti-CD28 antibody was sufficient to equip nTreg to suppress allograft rejection long-term in an experimental transplant model. Materials and Methods: Freshly-isolated nTreg were positively selected from CBA CD4+ splenocytes using anti-CD25 microbeads through a MACS column. CD4+CD25+ nTreg were activated in vitro using plate-bound anti-CD3 and antiCD28 monoclonal antibody over a period time and their surface markers were examined by flow cytometry. The final nTreg population–designated as “activated nTreg” were administered to CBA recipients 3 days prior to the implant of a C57BL/6 heterotopic heart allograft. A sub-optimal CTLA-4Ig (abatacept) was given peri-operatively on day 0, +1, + 5. In 2 separate groups, freshly-isolated or nTreg expanded using the same protocol over 5 days were given to CBA recipients instead. Results: Untreated CBA mice acutely rejected C57BL/6 allografts with a median

© 2014 The Authors. BJU International © 2014 BJU International | 113, Supplement 3, 1--37

survival time (MST) of 8 days (n = 10). Sub-optimal CTLA-4 Ig treatment prolonged graft survival to an MST of 50 days (n = 8). When given in combination with sub-optimal CTLA-4Ig, neither freshly-isolated nTreg, nor expanded nTreg prolonged allograft survival long-term (MST = 24 days, n = 8; MST = 40 days, n = 5, respectively). However, in clear contrast, activated nTreg prevented allograft rejection long-term beyond 100 days (n = 6). Conclusions: A short-course of polyclonal activation alone could equip naturallyoccurring regulatory T cells with effective suppressive function, without the need for expanding them in large numbers. These findings could potentially aid to resolve some of the logistic issues currently hindering the clinical application of Treg therapy in transplantation. TOP-08 A study of penile corporal healing after distal corporo-glanular shunt procedure using a novel rat model K.C.J. LEE*, L.DE YOUNG†, F.J. GARCIA† and G.B. BROCK† *Department of Urology, National University Hospital, Singapore; †Division of Urology, St Joseph’s Health Care, London, ON, Canada

Introduction: Distal penile corporo-glanular shunt procedures are commonly done for patients with major ischemic priapism. Many of these patients develop irreversible penile fibrosis and erectile dysfunction which require penile implants subsequently. Early insertion of penile prosthesis can be associated with concern of corporal perforation requiring surgical revision at the shunt site. Delayed insertion is technically more difficult due to dense corporal fibrosis that has formed. To date, there is no animal model that allows us to study distal corporal healing and the tensile strength of corporal scar tissue over time. The objective of our work was to develop a rat model to study distal corporal healing and evaluate the tensile strength of corporal scar tissue over time. Materials and Methods: Corporo-glanular shunt procedures were performed on 28 anesthetised male Sprague-Dawley rats after erection had been created using a vacuum device and constrictive band. A T-shunt was created in the left distal corpora followed by intracavernosal dilation. Strength-testing of corporal tissue on the 7

8 Abstracts

Mean maximal Tensile Strength (N)



Mean weight of Rat (g)

1 2 3 4 5 6 7

4 4 4 4 4 4 4

615 610 598 595 615 568 543

Right (Control)

Left (Ex-Shunt)

Tissue Strength Recovered (%)

3.84 2.24 2.41 2.91 4.40 2.62 2.61

1.87 1.13 2.35 2.58 4.00 2.35 2.93

48.7 50.5 97.7 88.7 90.9 89.9 112.6

right control side and left ex-shunt side was done using a customised intra-cavernosal force gauge daily from Day 1–7. The maximal tensile strength was measured by the peak force needed to perforate the corporo-glanular junction. Results: The intra-cavernosal probe on a force gauge allowed reliable measurement of corporal tissue strength. The ex-shunt side showed close to 90% recovery of tissue strength starting from Day 3 with maximal tissue strength achieved on Day 7. Conclusions: Penile corporal healing and tensile strength can be evaluated using this rat model. Complete distal corporal tissue strength recovery was achieved 7 days after injury*. *The time course of wound recovery in the rat is different from man and generally believed to be 15–30 fold more rapid. Further studies in man are required to better determine the rate of corporal healing.

Clinical Moderated Poster Presentation MP-01 Initiating a robotic partial nephrectomy programme following a robotic prostatectomy fellowship: Are the technical skills transferable?

L. TAN*, B. CHALLACOMBE‡, A. PATEL‡, R. WESTON§, G. COUGHLIN¶, D. MOON† and D.G. MURPHY† *Department of Urology, National University Hospital, Singapore; †Division of Cancer Surgery, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia; ‡ Department of Urology, Guy’s and St Thomas’ Hospitals, London, UK; §Department of Urology, Royal Liverpool Hospital, Liverpool, UK; ¶Department of Urology, Royal Brisbane Hospital, Brisbane, Queensland, Australia 8

Introduction: Robotic partial nephrectomy (RPN) is a technically demanding advanced minimally invasive procedure. Longer warm ischaemic times and increased blood loss could be anticipated in the initial learning curves. Fellowship experience in robotic radical prostatectomy may enable rapid transfer of skills to RPN. There are currently limited dedicated RPN fellowships. We looked at 4 centres commencing RPN with robotic prostatectomy fellowship trained surgeons. Materials and Methods: We reviewed a combined prospective consecutive case database from 4 centres initiating RPN with fellowship-trained surgeons. Standard metrics were recorded as well as operative time, warm ischaemic time, margin status, Clavien complications, renal function, hospital stay and Padua score. Results: Of 80 cases the mean tumour sise was 2.8 cm (range 1.1–5.8), the mean operating time 168 minutes (132–297) and the mean estimated blood loss 141 mls (30–600 mls). Mean PADUA score was 7 (range 6–9). The mean warm ischaemic time was 17.0 minutes (6–30) with 3 procedures performed off clamp entirely. Mean hospital stay was 3.6 days (2–15). There were 3 focal positive margins (2 with deep base biopsies clear) and there have been no recurrences at a mean follow-up of 13 months. I procedure was converted to a laparoscopic nephrectomy due to robot failure and one to open partial nephrectomy due to failure to progress. 15 masses were benign (18%) in pathology with the remaining 65 (82%) malignant. 1 patient required a ureteric stent for clot colic (Clavien IIIb) and 1 needed ITU support for COPD (IV). There were no significant drops in

creatinine/eGFR (>5%) and no blood transfusions were required. Conclusions: RPN following a dedicated robotic radical prostatectomy fellowship provides good early results with excellent functional and early oncological results. Warm ischaemic times are in line with the current best published series. Advanced robotic skills acquisition during fellowship training is likely to have contributed to this success. MP-02 Screening for asymptomatic bacteruria at one month after adult kidney transplantation: clinical factors and implications Y.S.B. GOH*, Z.L. DENG†, P.S.C. CHEONG†, L. RAMAN*, T.H.A. GOH‡, V. ANANTHARAMAN‡ and H.Y. TIONG* *Department of Urology, National University Health System, Singapore; †Yong Loo Lin School of Medicine, National University of Singapore, Singapore; ‡Department of Nephrology, National University Health System, Singapore

Introduction: Urinary tract infections (UTI) are a significant cause of morbidity after kidney transplantation. Screening for asymptomatic bacteruria has proven beneficial in certain adult groups such as pregnant women; but it is poorly studied in the transplant population. This study reviewed the incidence, clinical features and implications of asymptomatic bacteruria at one month after kidney transplantation. Materials and Methods: A review of 176 adult kidney transplant patients (87 (50.9%) Males, 86 (50.3%) living transplants, mean age 47.3  13.7), receiving conventional immunosuppression between 2005 and 2012, was performed. Protocol urine cultures were taken at 1 month after transplantation for all patients, regardless of symptoms. Five patients were excluded with missing culture results. Bacteruria was defined as >105 colony forming units of pathogenic organism per ml of clean catch voided urine specimen. All patients with positive cultures were treated with appropriate antibiotics. Patients were analysed according to culture positivity for baseline demographics and clinical factors. Outcomes in terms of hospitalisation for symptomatic UTIs, graft and patient survival were ascertained. Results: Among the 171 one-month urine cultures, 41 (24%) were positive for

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Abstracts 9

asymptomatic bacteruria. Klebsiella penumoniae, Escherichia coli and Enterococcus faecalis were the most common infective organisms, accounting for 34.1%, 26.8% and 22.0% of the isolates respectively. In addition, multi-resistant organisms accounted for 43.9% of the infections. Bacteruria was found to be associated with deceased donor transplants (p < 0.001) and female recipients (p = 0.014). It was not associated (p = NS) with recipient age, race, native kidney disease, donor demographics, and regimen of induction or maintenance immunosupression, occurrence or delayed graft function and duration of ureteric stent. Logistic regression confirms female sex (RR 2.6 95% CI 1.2– 5.6, p < 0.001) and deceased donor recipients (RR 7.7 95% CI 1.9–3.1, p = 0.02) were independent predictors of bacteruria at 30 days. Patients with bacteruria at 1 month were significantly more likely to be hospitalised subsequently for symptomatic UTI treatment (RR 4.6 95% CI 2.1– 9.9, p < 0.001). However, there was no significant difference in one-year patient (100% vs. 97%) and graft survival (95.1% vs. 95.4%) between the positive and negative bacteruria group. Conclusion: Asymptomatic bacteruria 30 days post transplant can be predicted in deceased donor and female recipients, probably due to functional and anatomical differences in voiding function respectively. It is predictive of increased morbidity of subsequent hospitalisation for symptomatic UTI and high risk groups may warrant targeted prophylaxis. MP-03 Using the European organisation of research and treatment of cancer risk tables for predicting recurrence & progression in non-muscle invasive bladder cancer: a local single centre experience S.L. LEE, S.K. LIM, K.K. NG and F.C. NG Department of Urology, Changi General Hospital, Singapore

Introduction: Application of the European Organisation of Research and Treatment of Cancer (EORTC) risk tables is recommended for the individual prediction of recurrence & progression risks in nonmuscle invasive bladder cancer (NMIBC). However, the EORTC risks tables are based on a Western population and may

not necessarily apply to our local Asian population. Aim: To compare the actual rates of recurrence & progression in our local study population against the predicted rates using the EORTC risks tables. Materials and Methods: We performed a retrospective review of 103 patients who were entered into our centre’s bladder cancer database. 75 patients (72.8%) with NMIBC were included in this study. 46 patients (61.3%) received intravesical therapy. Their recurrence & progression status at 1 year were recorded. Their outcomes were compared with the EORTC’s predictive scores. Results: Of the 75 patients, 60 were male & 15 were female, with an age range of 31 to 91 years (mean 65.6  13.9 years). 46 patients (61.3%) had stage Ta disease; 31 (41.3%) had high grade disease; 5 (6.7%) had presence of CIS; 18 (26.5%) had tumours 3 cm or greater in sise; & 34 (45.3%) had multiple tumours. Overall, recurrence occurred in 30 patients (40.0%) while progression occurred in 7 patients (9.3%). The recurrence rate at 1 year was 29.4%, 20.8%, 54.2% & 100% in the EORTC groups with predicted recurrence risks of 15%, 24%, 38% & 61% respectively. The progression rate at 1yr was 0%, 0%, 10% & 0% in the EORTC groups with predicted progression risks of 0.2%, 1%, 5% & 17% respectively. Conclusions: Our study showed higher recurrence rates as compared to the EORTC risk model, which may be the result of our local Asian population being different from the Western population on which the EORTC risk tables were created. We suggest a larger study cohort in order to validate the EORTC risks tables & to possibly develop a risk calculator for NMIBC in our local Asian population. MP-04 Predictive factors for recurrence & progression in patients with intermediate & high risk nonmuscle invasive bladder cancer: a local single centre experience

ing systems to predict recurrence & progression risk in non-muscle invasive bladder cancer (NIMBC). Aim: To identify which clinical, surgical & pathological factors were predictive for recurrence and progression in intermediate & high risk NMIBC in our local population. Materials and Methods: We performed a retrospective review of 103 patients who were entered into our centre’s bladder cancer database. Results: 76 patients (73.8%) had NMIBC, of which 14 had intermediate risk & 42 had high risk disease. Of these 56 patients, 45 were male & 11 were female, with an age range of 31 to 90 years (mean 65.2  14.3 years) with a mean follow-up duration of 41.2  31.2 months. 26 patients (46.4%) had stage Ta disease; 31 (55.4%) had high grade disease; 6 (10.7%) had presence of CIS; 18 (32.1%) had tumours 3 cm or greater in sise; & 32 (57.1%) had 2 or more tumours. Recurrence occurred in 25 patients (44.6%) while progression occurred in 7 patients (12.5%). Of the various factors studied, presenting complaint of gross haematuria (odds ratio 4.27, p = 0.015); & tumour sise ≥4 cm (odds ratio 13.33, p = 0.005) increased risk of disease recurrence. Multivariate analysis revealed both factors to significantly increase the risk of recurrence (gross haematuria, p = 0.023 & tumour sise ≥4 cm, p = 0.020 respectively). Risk of disease progression was increased by presenting complaint of gross haematuria (odds ratio 11.32, p = 0.028); & presence of 2 or more tumours (odds ratio 12.06, p = 0.025). Conclusions: Our study showed that factors such as presenting complaint of gross haematuria & tumours ≥ 4cm in sise; presence of 2 or more tumours significantly increased the risk of recurrence and progression respectively in intermediate & high risk NMIBC.

S.L. LEE, S.K. LIM, K.K. NG and F.C. NG Department of Urology, Changi General Hospital, Singapore

Introduction: Various factors including tumour sise, number of tumours, T stage, tumour grade, presence of carcinoma in situ (CIS) have been used in various scor-

© 2014 The Authors. BJU International © 2014 BJU International | 113, Supplement 3, 1--9


10 Abstracts

MP-05 Intraprostatic botulinum toxin injection for benign prostatic hyperplasia: a meta-analysis of prospective studies

MP-06 Australian experience and medium term outcomes of a new technique for panurethral stricture diseaseKulkarni’s Panurethroplasty

ture is difficult. A new single stage technique, the Kulkarni panurethroplasty, has emerged with improved cosmesis and excellent medium term results.

S.I. ALPAJARO and E.U. LIM University of Santo Tomas Hospital, Manila, Philippines

J. CHEE Alfred Hospital, Melbourne, Victoria, Australia

MP-07 Intravesical IFN-a and BCG immunotherapy for patients with recurrent bladder cancer after previous BCG therapy

Introduction: This meta-analysis aims to evaluate the efficacy and safety of Botulinum toxin type A (BoNT/A) intraprostatic injection for Benign Prostatic Hyperplasia (BPH) based on published prospective human trials. Materials and Methods: A thorough search of the Cochrane Database and PUBMED was done. The following criteria were used for selection of studies for this meta-analysis: 1. Articles published in English with prospective data assessing the efficacy and safety of BoNT/A for BPH; 2. Intraprostatic BoNT/A given at doses 100– 200 U; 3. Outcome measures of Peak Urinary Flow Rate (Qmax), Post-void Residual Volume (PVR), and Total Prostatic Volume; 4. Baseline and at least 3 months follow-up of the said outcomes. The Newcastle-Ottawa Scale was used to evaluate the quality of the primary studies. Variables were analysed using risk ratio (RR). Data analysis was done with Cochrane Collaboration’s Review Manager (RevMan) 5.2 software. The confidence interval (CI) was set at 95% and significant at p < 0.05. Results: Eight articles, involving 168 patients, were eligible for this review. Meta-analysis showed significant increase in Qmax (mean increase 2.61 ml/sec, 95% CI, 2.18 to 3.04, p < 0.0001), significant decrease in PVR (mean decrease 18.97 ml, 95% CI, 27.07 to 10.86, p < 0.0001), and significant decrease in prostatic volume (mean decrease 1.03 cm3 95% CI, 1.30 to 0.77, p < 0.0001). Reported adverse events were mild dysuria (22.9%) and minimal hematuria (17.5%). Conclusions: Intraprostatic BoNT/A injection appears to be an effective and safe treatment of BPH and its associated symptoms.


Introduction: Patients with panurethral and complex peno-bulbar urethral stricture disease are difficult to treat successfully. Traditional techniques to treat long urethral strictures include the Johansons two-stage urethroplasty and the fasciocutaneous penile flap described by McAninch. Both of these techniques require extensive surgery on the penile and scrotal skin. With the increasing use of oral mucosal graft and desire to preserve cosmesis and anatomy of the penis, Kulkarni et al. described the use of long oral mucosa grafts to repair the entire anterior urethra through a simple perineal incision in a single stage. I present my personal experience and outcomes of Kulkani’s panurethroplasty. Materials and Methods: From March 2011 to December 2012, a single surgeon performed 11 consecutive cases of Kulkarni’s panurethroplasty. Description of technique aided by 35 images. All data was prospectively collected in an electronic database. Pre operative variables included etiology, location, length of stricture, number of previous surgeries, smoking history, diabetes, erectile function, BMI, and pre operative voiding flow rates. Operative variables collected included time of surgery, number of oral grafts required, site of oral grafts, total length of oral grafts harvested. Any complications were recorded and functional outcomes were determined by voiding flow rates at 6 weeks, 3 months, 6 months and 12 months post-op. Success was defined as a voiding flow rate of >15 mls/sec. Results: 10 of the 11 cases were “successful” with a mean VFR of 23 mls/sec and a minimum follow-up of 12 months. A single patient had a VFR of 12 mls/sec at 12 months. This patient is still extremely happy with the results (his pre-op VFR was 4 mls/sec despite alternate day intermittent self dilatation) and he does not currently want any further surgical intervention. There were no significant complications. Conclusions: The management of panurethral or complex long peno-bulbar stric-

J. RAHMAT*, L. RAMAN*, Y.H. CHAN†, R. MAHENDRAN*, E. CHIONG* and K. ESUVARANATHAN* *Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; †Biostatistics Unit, Yong Loo Lin School of Medicine, National University of Singapore, Singapore

Introduction: Intravesical instillation of Bacillus Calmette-Guerin (BCG) with Interferon-a (IFN-a) in a 15-month schedule is effective in patients with recurrence of nonmuscle invasive bladder cancer (NMIBC) after previous BCG therapy but the toxicity often prevents completion of therapy. The aims of this Phase II study were to determine the efficacy and toxicity of a novel short course of BCG and IFN-a. Materials and Methods: Patients with recurrent high risk bladder tumours, who were surgically unfit or had rejected cystectomy, underwent transurethral resection followed by a combination of low dose BCG (27 mg) and IFN-a (10 million U) instillations in a “4 + 2” schedule of weekly instillations with an interval of 6 weeks between the courses. Urine samples were assayed for several cytokines (IL-8, IL-10, IL-2, IFN-c and TNF-a). Patient diaries were maintained to record toxicity. Patients were followed-up for 5 years. Toxicity symptoms of patients with and without local recurrence were compared using Fischer’s exact test. Results: Of 16 patients, 8 remained disease-free at a median 50.7 months followup. Mean time to recurrence was 37.2 months (95% CI, 20.4–54.0) and the 5-year local recurrence-free survival was 45.1% (95% CI, 19.0–71.2). The 5 year probability of survival was 58.9% (95% CI, 27.5–90.3). Non-recurrent patients had significant incidence of fever during the induction course (p = 0.007). BCG responders steadily produced increasing levels of urinary cytokines during the initial course while BCG non-responders had a plateau or a drop in cytokine levels by

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Abstracts 11

the 3rd or 4th instillation. BCG nonresponders displayed higher levels of basal urinary cytokines prior to start of therapy. Conclusions: This novel short course of BCG plus IFN-a was well tolerated in BCG failures and had similar efficacy to other published protocols. However, the high mortality rate underscores the urgent need for new therapies in patients who are unfit to undergo radical cystectomy. MP-08 Predictive factors for benign pathology in renal tumours X.L. TEO, S.K. LIM, K.K. NG and F.C. NG Department of Urology, Changi General Hospital, Singapore

Introduction: The incidence of benign renal masses has increased along with the incidence of renal cell carcinoma as a result of increased usage of radiological imaging. This study aims to determine parameters to predict benign pathology for patients with suspected RCC in our local population. Materials and Methods: A retrospective review of patients with histologically proven renal masses between 1994 and 2012 was performed. Demographic features, symptoms at presentation and CT scan findings were analysed. Results: Eighty nine patients were included in the analysis. There were 12 (13.5%) patients with benign renal lesions. Of which, 8 lesions were angiomyolipomas, 2 lesions were oncocytomas and 1 patient each had an encapsulated hematoma and papillary adenoma. The mean age of these patients was 60.9 years (29– 88 years). Eight (26.7%) females and 4 (6.8%) of males were diagnosed with benign lesions. Females were more likely to be diagnosed with benign lesions (p = 0.018) 38 (43.2%) patients had incidental finding of renal masses on radiological imaging and patients with such incidental findings were more likely to have benign lesions (p = 0.026). The mean sise of benign tumours was 3.4 cm, compared to 6.1 cm for RCC. Benign lesions were more like to be smaller (12.0 ml/s. Their mean age was 66.3 years. 14 of these patients had BOO, and the distribution of their IPP is as follows: Grade 1 (10 mm): 17 out of 20 (85%). IPP grade was a significant predictor of BOO in these patients (p = 0.0027). 19 patients with good urinary flow underwent TURP eventually and 16 had BOO. There were no significant differences in the num-

ber of patients requiring TURP between those with BOO and those without (p = 0.088). Out of the 19 who underwent TURP, 3 had grade 1 IPP, 6 had grade 2 IPP and 10 had grade 3 IPP (p = 0.044). Conclusion: Patients with good urinary flow may still have BOO on urodynamic studies. However, urodynamic obstruction in patients with good flow was not associated with an eventual need for surgery. A higher grade of IPP is positively correlated to BOO even in good flow and is a useful adjunct to predict the eventual need for surgery. MP-17 Patients with small prostate and low-grade intravesical prostatic protrusion presenting with bladder outlet obstruction–A case series study

H.J. LEE*, A. LEE*, P. SUNDARAM†, N. GOH† and K.T. FOO† *Yong Loo Lin School of Medicine, National University of Singapore, Singapore; † Department of Urology, Singapore General Hospital, Singapore

Introduction: High-grade intravesical prostatic protrusion (IPP) is closely related to bladder outlet obstruction (BOO), but up to 21% of patients with grade 1 IPP are still obstructed. Our objective is to examine the natural history of patients with a small prostate volume (PV) and low grade IPP presenting with obstruction and their response to different management plans, including an assessment of the patients who eventually required surgery. Methods: Patients with grade 1a prostates (prostate volume 7 cm and Fuhrman grade 3/4 significantly predict late recurrences. This study can help individualise long term FU plans for patients. UP-27 Prognostic factors for oncological outcomes following surgery in patients with upper tract urothelial carcinoma with no distant metastasis S. YEOW, Z. LIU and K.T. CHONG Department of Urology, Tan Tock Seng Hospital, Singapore

Introduction: This study was done to review a single-centre tertiary centre’s outcome for patients with upper urothelial tract carcinomas (TCC) post-surgical resection and to determine the relevance of both traditional prognostic factors and possible new prognostic factors. Materials and Methods: All patients who had undergone nephroureterectomy for upper tract TCC at a tertiary hospital in Singapore between May 2008 and May 2013 were retrospectively identified. Those with non-TCC on final histology were excluded. Prognostic factors examined included patient characteristics, operative factors and disease characteristics. Results: A total of 43 eligible patients (30 male) were identified. 21 underwent laparoscopic nephroureterectomy, 21 underwent open nephroureterectomy, and 1 patient had laparoscopic converted to open surgery. Recurrences were most commonly found in the bladder, regardless of presence of prior bladder tumours.Male gender was associated with a non-significant trend towards lower disease recurrence. The mean time to recurrence was 37.4 months (95% CI: 26.5–48.3), median time to recurrence was 22 months (95% CI: 8.3–35.7). Three-year disease-free survival was 37.8%. The mortality rate was 14.3% for death due to all causes; of which 4 were due to disease (9.3%). The mean time to death was 67.7 (95% CI: 59.4– 76.0). (See Figure 2) Conclusions: 51.2% of our study population had disease recurrences, with a med-

ian time to recurrence of 22 months. Tumour stage and grade were significant for tumour recurrence. UP-28 Validation of a novel Asian dietary questionnaire in assessing nutritional risk factors for urinary stone formation A. YUWONO1, K. SUNDARAM2, M. SHEN3, K.S. PNG1 and S.J. CHIA1 1 Department of Urology, Tan Tock Seng Hospital, Singapore; 2Department of Nutrition and Dietetics, Tan Tock Seng Hospital, Singapore; 3Clinical Research Unit, Tan Tock Seng Hospital. Singapore

Introduction: Nutritional risk factors for lithogenesis can be identified using a detailed three-day food diary, which is analysed and interpreted by a registered dietician. An individually tailored dietary advice can be given based on the food diary. However, some individuals may find completing a food diary to be cumbersome. Additionally, many urologists do not have access to a registered dietician. A novel dietary questionnaire, tailored to local food and beverages in Singapore was developed to identify dietary lithogenic risk factors Material & Methods: A 36-item dietary questionnaire was developed, which quantified intake of stone inhibitors (citrate and fluids), stone promoters (animal protein and oxalate) and calcium. Twenty healthy volunteers were recruited to complete the dietary questionnaire. They were then asked to complete a three-day food diary. Using the food diary, a dietician conducted a telephone interview for 24-hour diet recall. The responses to the dietary questionnaire were compared with the nutrient analysis of 24-hour diet recall. The dietician was blinded to the data in the questionnaire. Pearson’s correlation analysis was used to determine the relationship between the two variables. Results: The questionnaire required approximately five minutes to complete. Amount of fluid intake was well-captured on the questionnaire (r = 0.55; moderate positive linear relationship, p = 0.01). Strong positive linear relationship was observed for calcium intake (r = 0.87, p < 0.01). No linear relationship noted for animal protein intake on the questionnaire

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Abstracts 37

(r = 0.08, p = 0.73). From the questionnaire, subjects responded average consumption of citrate-rich food (orange, lime, pineapple) of 1-2 times/month. On average, oxalate-rich food (bai-cai, tofu,

tempeh) was consumed on a weekly basis. Both of these corresponded well with the 24-hour diet recall. Conclusions: The lithogenic dietary questionnaire provides a simpler tool in identi-

© 2014 The Authors. BJU International © 2014 BJU International | 113, Supplement 3, 1--37

fying stone-related nutrition factors compared to a three-day food diary and 24-hour food recall. Validation of this tool will allow future studies on dietary patterns of stone-formers to be conducted.


Abstracts of the UROFAIR 2014, Changing Paradigms in Urology, March 6-8, 2014, Suntec, Singapore.

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