498 THE EFFECT OF DEEP BRAIN STIMULATION ON VOIDING DYSFUNCTION IN PARKINSON'S DISEASE AND ESSENTIAL TREMOR

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Effect of sub-thalamic stimulation in lower urinary tract symptoms Pinto R.1, Oliveira R.1, Silva A.1, Lopes T.1, Silva J.1, Silva C.1, Guimarães M.1, Rosas M.J.2, Vaz R.3, Cruz F.1 Hospital De São João, Dept. of Urology, Porto, Portugal, 2Hospital De São João, Dept. of Neurology, Porto, Portugal, 3Hospital De São João, Dept. of Neuro-Surgery, Porto, Portugal

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Introduction & Objectives: Micturition is a complex act dependent on multiple nuclei and neuronal pathways, the most important nuclei being the pontine micturition centre. Periaqueductal grey matter, thalamic and sub-thalamic regions seem to be relay stations for sensory inputs arriving from sacral spinal cord neurons. These nuclei are closely located to the areas that have been being electrically stimulated to treat Idiopathic Parkinson’s Disease (IPD). In this work we evaluated the effects in lower urinary tract symptoms and urodynamic parameters in patients with IPD submitted to sub-thalamic neuronal stimulation (STNS). Material & Methods: Fifteen patients with IPD who underwent implantation of neurostimulators (NS) were clinically evaluated and they were asked to fill in a three days voiding chart, the IPSS, the QoL score from IPSS, at baseline and one, three and six months after the procedure. Urodynamic studies including urofluxometry and pressure-flow studies were performed at the same time points. Data were compared by a Student’s t test. A p<0.05 was considered statistically significant. Results: At baseline, medium IPSS and QoL scores were 9.2 (5-14, ± 2.9) and 2 (1-4, ± 1.4), respectively. Eight patients had overactive bladder (OAB) symptoms, 3 with OAB wet and 5 with OAB dry. At urodynamics, 7 of these patients had detrusor overactivity. At one month of follow-up, medium IPSS and QoL scores increased to 11.7 (7-17, ± 3.0, p<0.05) and 3 (1-5, ± 0.7, p>0.05), respectively. All patients referred either worsening of previous urgency or de novo urgency (p<0.05). Urinary incontinence was present in 7 patients (3 of them with OAB wet at baseline, 2 with OAB dry at baseline and another 2 without OAB symptoms at baseline). Urodynamic studies demonstrated detrusor overactivity in 11 patients. The medium bladder volumes to first and strong desire to void and the cistometric capacity decreased from 201.5 to 107.5 ml, from 416.5 to 181.5 ml and from 445 to 344 ml, respectively (p<0,05). The bladder medium volume to first detrusor contraction also decresead significantly (from 280 to 146 ml, p<0,05). There were no significant differences between baseline values and those found three and six months after the procedure. OAB symptoms also subsided in those patients without OAB previously to the procedure. Conclusions: STNS causes transient urgency during first weeks of treatment and lower bladder volumes to void and lower maximum cystometric capacity accompany it. These side effects are probably due to acute electrical stimulation of nearby brain nuclei that vanishes with treatment continuation. These informations are important for counseling new IPD patients proposed for STNS.

P31 PROSTATE CANCER TUMOUR CELL BIOLOGY Thursday, 19 March, 14.00-15.30, Room A3

499

Systematic analysis of inoculation techniques for orthotopic prostate tumours in mice and usability of three-dimensional ultrasound micro imaging to monitor tumour growth Saar M.1, Kamradt J.1, Jung V.1, Suttmann H.2, Körbel C.3, Stöckle M.1, Menger M.D.3, Unteregger G.1 University of Saarland, Dept. of Urology and Pediatric Urology, Homburg/Saar, Germany, Urologikum Hamburg, Dept. of Urology, Hamburg, Germany, 3University of Saarland, Institute for Clinical and Experimental Surgery, Homburg/Saar, Germany

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Introduction & Objectives: Prostate cancer tumour models are a growing part of experimental research and different approaches were undertaken to overcome the limitation of permanent cell lines. It is evident that cancer cells outside their natural milieu behave quite differently than they do in their organ of origin. Thus, orthotopic inoculation of tumour cells into the prostate of mice seems to be more promising compared to ectopic sites. Orthotopic inoculation of prostate cancer cells has already been described but most of these studies lack of a detailed methodical description and fail to use highly standardized inoculation techniques. Moreover, monitoring of tumour growth after surgical inoculation has so far been limited to autopsy and histology as the only reliable methods to evaluate tumour formation and treatment efficacy. In this study, a three-dimensional ultrasound micro imaging technology is used for the first time to monitor tumour progression after surgical orthotopic inoculation of cancer cells. Material & Methods: We investigated the effect of different inoculation protocols on tumour growth and progression using 30 eight week old Crl:CD1-Foxn1nu mice. After abdominal laparotomy using a surgical microscope, we injected 10µl of prostate carcinoma cells from the subline DU 145 MN1 into different prostatic lobes with a Hamilton syringe (26 gauge pst2 needle). We used (i) different cell amounts (5x105 or 5x104) (ii) varied the number of punction sites and (iii) added cell culture medium RPMI +/- Matrigel™. Complications such as (i) recoil of cells through the injection canal and (ii) rupture of prostatic capsule were monitored. Animals were tracked throughout a 6-week period performing ultrasound imaging four, five and six weeks after surgical inoculation. Video imaged autopsy and histology were used to ensure orthotopic tumour growth.



498

The effect of deep brain stimulation on voiding dysfunction in Parkinson’s disease and essential tremor Vishwajit S.1, Dave M.1, Siddiqui M.2, Cartwright D.1, Patel B.N.1, Badlani G.H.1 1 2

Wake Forest, Dept. of Urology, Winston-Salem, United States of America, Wake Forest, Dept. of Neurology, Winston-Salem, United States of America

Introduction & Objectives: There is a well described body of literature regarding the high incidence of voiding dysfunction in patients with Parkinson’s disease (PD). Essential tremor (ET), present in 5 % of adults, is often confused with PD and is also associated with voiding dysfunction. The aim of this study was to compare and evaluate the efficacy of deep brain stimulation (DBS) on the sub-thalamic, ventricular, and globus nuclei on voiding symptoms in patients with PD and ED. Material & Methods: 45 patients with PD or ET were identified through the department of Neurology. They each participated by completing a questionnaire documenting symptoms associated with bladder storage and emptying symptoms before the initiation of and after the completion of DBS. Results: 45 patients, 30 with PD and 15 with ET were studied. Of the 30 patients with PD, 19 had urinary incontinence; 21% had improvement of their symptoms, while 79% had no change or had worsening incontinence after DBS. 24 PD patients had urinary urgency; 30% had improvement of their symptoms while 70% had no change or worsening of their symptoms after DBS. 26 PD patients had nocturia; 12% improved and 88% had no change or worsening of their symptoms after DBS. Of the 15 patients with ET, 4 had urinary incontinence and 7 had urinary urgency, none of these patients improved with DBS. 10 ET patients had nocturia with only 20% having improvement in their symptoms after DBS. Conclusions: Although DBS may play an effective role in managing the voiding and storage problems in patients with PD, there seems to be less of a role in patients with ET.



500

A novel androgen-dependent prostate cancer xenograft model derived from skin metastasis of Japanese patient Kimura T.1, Kiyota H.1, Nakata D.2, Masaki T.3, Kusaka M.3, Egawa S.1 Jikei University School of Medicine, Dept. of Urology, Tokyo, Japan, 2Takeda Pharmaceutical Company Ltd, Pharmacology Research Laboratories Ii, Osaka, Japan, 3 Takeda Pharmaceutical Company Ltd, Strategic Research Planning Department, Osaka, Japan

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Introduction & Objectives: The incidence and mortality of prostate cancer (PCa) among Asian countries have been increasing for the last decades because of a change in dietary habits. Recent reports revealed differences of molecular basis of PCa among racial/ethical background. To understand basis of PCa of Asian population, PCa xenograft models established from Asian patients is thought to be very useful. However, most of models are established from Caucasian or black patients and models from Asian patient are extremely rare. In the present study, we established and characterized a novel PCa xenograft model, JDCaP, from skin metastasis lesion of Japanese hormone-refractory prostate cancer (HRPC) patient. Material & Methods: Skin metastatic tissue from 61-year-old Japanese patient was transplanted to nude mice and the stable cell line, JDCaP, was established by serial passages. Expression of androgen receptor (AR) and prostate specific antigen (PSA) was evaluated by immunohistochemistry and sequence of AR was analyzed. Hormone dependency of JDCaP was observed in vivo by orchiectomy and administration of steroid hormones including testosterone, estradiol, progesterone and hydrocortisone. Therapeutic effect of leuprorelin acetate, bicalutamide, flutamide, diethylstilbestrol (DES) and estradiol was observed.

Results: We demonstrate that (i) orthotopic tumour inoculation and intraprostatic tumour growth is possible in 27 of 30 consecutive animals; (ii) ultrasound screening is a feasible way to monitor tumour growth; (iii) tumour size correlates to the amount of injected cells; (iv) addition of Matrigel™ seems to reduce tumour growth; (v) using 10µl cell suspension recoil is very rare (6,7%); (vi) rupture of prostate capsule (1,3%) avoids tumour formation without intraperitoneal growth.

Results: The established cell line, JDCaP expressed wild-type AR and PSA. Interestingly, JDCaP was androgen dependent even established from HRPC patient. Administration of testosterone kept proliferation of tumor after orchiectomy but other steroid hormones did not contribute for the proliferation. Administration of leuprorelin acetate, bicalutamide and flutamide showed growth inhibition of JDCaP. DES and estradiol also showed significantly strong anti-tumor effects.

Conclusions: Finally we conclude that standardized growth of orthotopic prostate tumour is best achieved by inoculation of 10µl with a high amount of cells under the capsule in single prostate lobes using a Hamilton syringe. Ultrasound examination allows monitoring of orthotopic tumour formation and further tumour growth in vivo. Based on these results we developed a less invasive method of percutaneous ultrasound guided inoculation of tumour cells into the prostate, that is evaluated in an ongoing experimental study.

Conclusions: We established a novel PCa xenograft model which is established from skin metastasis lesion of Japanese HRPC patient. PCa xenograft model from Asian patient is very rare. In addition, the tumor expresses wild-type AR sequences and hormone dependency even established from HRPC patients. The model should be useful to analyze the molecular biology of PCa in Asian population.

Eur Urol Suppl 2009;8(4):245