SCIENTIFIC PROGRAMME Tuesday 7th October 2003 09:00 - 10:30 Podium Session 1 Urodynamics 09:00 1 THE REPORTING QUALITY OF ABSTRACTS OF RANDOMISED CONTROLLED TRIALS

SUBMITTED TO THE ICS MEETING IN HEIDELBERG Herbison G P

09:15 2 NON-INVASIVE BLADDER PRESSURE: THE CASE FOR USING A MODIFIED ICS

NOMOGRAM Griffiths C, Blake C, Harding C, McIntosh S, Drinnan M, Robson W, Pickard R, Abrams P, Ramsden P

09:30 3 VALIDATION OF THE PENILE COMPRESSION-RELEASE MANOEUVRE FOR NON-

INVASIVE DIAGNOSIS OF BLADDER OUTFLOW OBSTRUCTION Harding C, Mcintosh S, Robson W, Ramsden P, Drinnan M, Griffiths C, Pickard R

09:45 4 IS THERE A ROLE FOR URODYNAMIC TEST ON CONSERVATIVE TREATMENT?

URODYNAMIC EVALUATION OF URINARY INCONTINENT WOMEN TREATED WITH PERINEAL MAGNETIC STIMULATION. Bruschini H, Almeida F, Srougi M

10:00 5 LEAK POINT PRESSURE TESTING AFTER TISSUE ENGINEERED SLING PLACEMENT IN

A MODEL OF STRESS URINARY INCONTINENCE Cannon T, Conway D, Lu S H, Xavier M, Fraser M O, Chermansky C, de Groat W, Huard J, Chancellor M

10:15 6 VLPP AND SURGICAL OUTCOME: PRELIMINARY DATA

Pajoncini C, Costantini E, Bini V, Tascini M C, Rociola W, Guercini F, Porena M 11:30 - 13:00 Poster Session 1 Basic Science 11:30 7 CELLULAR PROPERTIES OF HUMAN SUB-UROTHELIAL MYOFIBROBLASTS - THEIR

ROLE IN BLADDER SENSATION Fry C, Wu C, Sui G

11:37 8 DETRUSOR OVERACTIVITY INDUCED BY INCREASED LEVELS OF NERVE GROWTH

FACTOR IN BLADDER AFFERENT PATHWAYS IN RATS Satoshi S, Sasaki K , Igawa Y , Nishizawa O, Chancellor M , de Groat W , Yoshimura N

11:45 9 ELECTRICAL STIMULATION OF THE L6 AND S1 SPINAL NERVES REDUCES THE

BLADDER OVERACTIVITY INDUCED BY CYCLOPHOSPHAMIDE IN ANESTHETIZED RATS Allard J, Francomme C, Bernabé J, Denys P, Chartier-Kastler E, Giuliano F

11:52 10 SUPRASPINAL AMPA AND NMDA GLUTAMATERGIC TRANSMISSION IN THE

MICTURITION REFLEX IN THE URETHANE-ANESTHETIZED RAT Yoshiyama M, de Groat W

12:00 11 CANNABINOID THERAPY IN DETRUSOR OVERACTIVITY: LOCAL VERSUS SYSTEMIC

EFFECT IN A SPINALISED RAT MODEL Blyweert W, Van der Aa F , De Ridder D

12:07 12 ACTIVATION OF 5-HT7 RECEPTORS IS LIKELY TO BE RESPONSIBLE FOR 5-HT

EFFECTS IN THE RAT URINARY BLADDER Palea S, Lluel P , Barras M, Duquenne C, Galzin A, Arbilla S

12:15 13 SVT-40776, A NEW SELECTIVE M3 MUSCARINIC ANTAGONIST: HUMAN RECEPTOR

BINDING PROFILE AND BLADDER EFFECTS IN THE GUINEA PIG Salcedo C, Balsa D, Enrich A , Davalillo S , Pellicer T, Lagunas C , Catena J, Fernández-Serrat A, Farrerons C , Fernández A G

12:22 14 IN VIVO AND IN VITRO FUNCTIONAL CHANGES OF THE URINARY BLADDER IN MICE

LACKING MUSCARINIC M2 OR M3 RECEPTORS Igawa Y, Zhang X, Umeda M, Iwata A, Nishizawa O, Taketo M, Manabe T, Matsui M, Andersson K

12:30 15 COMPARISON OF EFFECTS OF VARIOUS ANTIMUSCARINIC DRUGS ON

NORADRENALINE RELEASE FROM HUMAN ISOLATED URETHRA Yoshida M, Miyamae K, Otani M, Iwashita H, Masunaga K, Inadome A, Ueda S

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12:37 16 EFFECT OF PROTAMINE PRETREATMENT ON DETRUSOR HYPERACTIVITY INDUCED BY INTRAVESICAL CAPSAICIN IN ANAESTHETIZED GUINEA-PIGS. Cialdai C, Lecci A, Lazzeri M, Giuliani S, Maggi C A, Turini D

12:45 17 NICOTINIC RECEPTORS MODULATED CONTRACTILE ACTIVITY AND COMPLIANCE OF

MUSCLE-DERIVED STEM CELLS INCORPORATED INTO ACELLULAR SCAFFOLDS FOR URETHRAL AND BLADDER RECONSTITUTION Lu S, Sacks M, Qu-Petersen Z, Peng H, Pruchnic R, Somogyi G, Cannon T, Huard J, de Groat W, Chancellor M

12:52 18 INTRAURETHRAL MUSCLE DERIVED CELL INJECTIONS INCREASE LEAK POINT

PRESSURE IN A RAT MODEL OF INTRINSIC SPHINCTERIC DEFICIENCY Chermansky C, Tarin T, Kwon D, Cannon T, de Groat W, Huard J, Chancellor M

11:30 – 13:00 Poster Session 2 Quality of Life 11:30 19 MEASURING QUALITY OF LIFE (QOL) IN MEN WITH URINARY SYMPTOMS: USING THE

WORLD HEALTH ORGANISATIONS INSTRUMENT WHOQOL-BREF Haltbakk J, Hanestad B R, Hunskaar S

11:37 20 PREDICTORS OF GENERAL HEALTH-RELATED QUALITY OF LIFE IN OLDER ADULTS

WITH URINARY INCONTINENCE Sereika S, Engberg S, Engberg R

11:45 21 NOCTURIA HAS A SIGNIFICANT IMPACT ON HEALTH-RELATED QUALITY OF LIFE

Coyne K, Zhou Z, Versi E 11:52 22 THE HEALTH-RELATED QUALITY OF LIFE (HRQOL) IMPACT OF THE SYMPTOMS OF

NOCTURIA IN PATIENTS WITH OVERACTIVE BLADDER Pleil A M, Kelleher C J, Allen L E, Ray Reese P

12:00 23 THE ASSOCIATION OF DIET AND OTHER LIFESTYLE FACTORS WITH OVERACTIVE

BLADDER:A LONGITUDINAL STUDY IN WOMEN. Dallosso H

12:07 24 SYMPTOMS, TREATMENTS AND QUALITY OF LIFE AMONG MEMBERS OF THE

INTERSTITIAL CYSTITIS SUPPORT GROUP IN THE UK Tincello D, Walker A

12:15 25 HEALTH-RELATED QUALITY OF LIFE IN ADOLESCENTS WITH SPINA BIFIDA: A

PROSPECTIVE MULTIDIMENSIONAL STUDY Rendeli C, Padua L, Ausili E, Girardi E, Caliandro P, Salvaggio E

12:22 26 PROPIVERINE VS. TOLTERODINE – EFFICACY AND TOLERABILITY IN PATIENTS WITH

DETRUSOR OVERACTIVITY Jünemann K P, Halaska M, Rittstein T , Bruenjes R

12:30 27 EVALUATION OF INCONTINENCE QUALITY OF LIFE (I-QOL) SUBSCALES IN PATIENTS

SUFFERING FROM DETRUSOR OVERACTIVITY(DO):IMPACT OF SACRAL NEUROMODULATION Cappellano F, Bertapelle P , Catanzaro F, Del Popolo G, Cervigni M, Spinelli M, Curti P, Minardi D, Leone G, Giardiello G, GINS Group O B

12:37 28 PATIENTS' VIEWS OF A COLOSTOMY FOR FAECAL INCONTINENCE

Norton C, Burch J, Kamm M A 12:45 29 THE OUTCOME OF TVT ANALYSED WITH DISEASE-SPECIFIC QUALITY OF LIFE

QUESTIONNAIRES: RESULTS FROM THE NETHERLANDS MULTICENTER TVT STUDY. Schraffordt S, Vervest H, Bisseling T

12:52 30 CURE: DO CLINICIANS KNOW BEST?

Robinson D, Anders K, Cardozo L, Bidmead J 14:00 - 15:30 Poster Session 3 Diagnostic Techniques 14:00 31 THE FLOW STUDY: VALIDATION OF FOUR QUESTIONNAIRES ON SYMPTOMS AND

QUALITY OF LIFE IN ITALIAN WOMEN WITH LUTS Tubaro A, Prezioso D , Zattoni F , Artibani W , Pesce F , Scarpa R M, Simoni L

14:07 32 EXPLORING THE USE OF FREQUENCY-VOLUME CHARTS

De Wachter S, Wyndaele J J

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14:15 33 THE EFFECT OF ANITCHOLINERGIC THERAPY ON URGENCY SEVERITY IN PATIENTS WITH OVERACTIVE BLADDER: CLINICAL ASSESSMENT OF A NEWLY VALIDATED TOOL Dmochowski R, Heit M, Sand P

14:22 34 PROSPECTIVE COMPARISON OF FREE FLOW RATE WITH FLOW

RATE OBTAINED FOLLOWING FLEXIBLE CYSTOSCOPY Weston R, Das S, Pace A, Powell C

14:30 35 HOW UROFLOWMETRY IS PERFORMED: RESULTS OF AN INTERNATIONAL SURVEY

AMONG ICS MEMBERS Artibani W, Pesce F, Rubilotta E, Aresu L, D'Amico A, Curti P, Cerruto M A

14:37 36 SATISFACTION GUARANTEED? THE URODYNAMIC EXPERIENCE

Dixon A, Anders K, Cardozo L, Robinson D 14:45 37 ACCEPTANCE AND MORBIDITY ASSOCIATED WITH URODYNAMIC STUDIES IN

PATIENTS WITH SPINAL CORD INJURY. Bycroft J, Wood S , Bywater H, Knight S, Craggs M, Shah J

14:52 38 ADVANCED 3D MODELLING. SIMULATION OF SQUEEZING AND VALSALVA

MANOEUVRES IN HEALTHY NULLIPAROUS WOMEN. Otcenasek M, Halaska M, Krcmar M, Blovsky J

15:00 39 NORMAL VALUES FOR PELVIC ORGAN DESCENT IN HEALTHY NULLIGRAVID YOUNG

CAUCASIAN WOMEN Dietz H P, Eldridge A, Grace M, Clarke B

15:07 40 BLADDER WALL THICKNESS AND THE OVERACTIVE BLADDER: DO CONTRACTIONS

COUNT? Robinson D, Anders K, Cardozo L, Dixon A

15:15 41 THE INFLUENCE OF TUR OR OPEN PROSTATECTOMY ON ULTRASOUND ESTIMATED

BLADDER WEIGHT (UEBW): A PROSPECTIVE STUDY ON 26 PATIENTS Canepa G, Capponi G, Campodonico F, Maffezzini M

15:22 42 A RANDOMIZED, CONTROLLED TRIAL OF THE USE OF ENDOANAL ULTRASOUND

AFTER DELIVERY TO DIAGNOSE ANAL SPHINCTER TEARS AND PREVENT FAECALINCONTINENCE Faltin D, Boulvain M, Floris L, Weil A, Irion O

14:00 - 15:30 Poster Session 4 Paediatrics and LUTS 14:00 43 VOIDED VOLUMES AND URINARY OUTPUT OF WATER AND SOLUTES, OVER A 72-

HOUR PERIOD, IN 62 NORMAL SCHOOL-AGE CHILDREN Van Hoeck K, Bael A M, Lax-Gross H, Hirche H, Vander Linden A , van Gool J D

14:07 44 THE INVESTIGATION AND SUB-CLASSIFICATION OF RENAL TRACT IMMATURITY IN

CHILDHOOD EURESIS USING NOVEL METABONOMIC TECHNOLOGY. Taylor C, Bollard M, Tang H, Mouriquand P, Foxall P

14:15 45 LONG TERM FOLLOW UP ON CONTINENCE AND RENAL FUNCTION IN 50 PATIENTS

WITH CAUDAL REGRESSION SYNDROME. A MULTICENTER STUDY. Buffa P, De Gennaro M, Battaglino F, Beseghi U, Di Lorenzo F, Urso S, Cama A

14:22 46 PERCEPTION OF THE NEED FOR A PAEDIATRIC BLADDER DYSFUNCTION QUALITY OF

LIFE MEASURE. Bower W, Yeung C

14:30 47 TIMED VOIDING THERAPY FOR CHILDREN WITH DAYTIME URINARY INCONTINENCE

ATTRIBUTABLE TO OVERACTIVE BLADDER Kajiwara M, Inoue K, Usui A, Usui T

14:37 48 BOTULINUM TOXIN A INJECTION IN THE M. DETRUSOR VESICAE REPLACES SURGERY

IN CHILDREN WITH MYELOMENINGOCELE Staehler M, Sauter T, Miller K

14:45 49 CANADIAN URINARY BLADDER SURVEY: POPULATION-BASED STUDY OF SYMPTOMS

AND INCONTINENCE Herschorn S, Corcos J, Gajewski J, Schulz J, Ciu E

14:52 50 INCREASED NOCTURNAL URINE VOLUME IS ASSOCIATED WITH A GONADOTROPIN-

INDEPENDENT REDUCTION OF NIGHTTIME SERUM TESTOSTERONE LEVEL IN MALE NOCTURIA PATIENTS Lin A T, Lin A D, Wang P S , Chen K K

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15:00 51 CHANGES OF URINARY NERVE GROWTH FACTOR AND PROSTAGLANDINS IN MALE PATIENTS WITH LOWER URINARY TRACT SYMPTOM Kim J C, Lim P B, Seo S I, Park Y H , Hwang T

15:07 52 THE CLINICAL EFFICACY OF NAFTOPIDIL ON OVERACTIVE BLADDER IN PATIENTS

WITH BENIGN PROSTATIC HYPERPLASIA Takahashi S, Takeuchi T, Tomita K, Homma Y, Kitamura T

15:15 53 TREATMENT STRATEGIES, PATTERNS OF DRUG USE AND TREATMENT

DISCONTINUATION IN MEN WITH LUTS SUGGESTIVE OF BENIGN PROSTATIC HYPERPLASIA - THE TRIUMPH PROJECT (1) Verhamme K, Dieleman J, Bleumink G , Bosch R , Stricker B, Sturkenboom M

15:22 54 RANDOMISED CONTROLLED TRIAL OF THE CLINICAL AND COST EFFECTIVENESS OF

EXISTING CONTINENCE SERVICES COMPARED WITH A NEW NURSE-LED SERVICE. Williams K, Assassa R P, Cooper N, Turner D, Shaw C, Abrams K, Mayne C, McGrother C

16:00 - 17:00 Podium Session 2 Paediatrics 16:00 55 A SUGGESTED TREATMENT ALGORITHM IN NOCTURNAL ENURESIS WITH EMPHASIS

ON PARTIAL RESPONDERS Marschall-Kehrel A, Mürtz G, Kramer G, Jünemann K

16:15 56 IS TRANSDERMAL ELECTRICAL STIMULATION A THERAPEUTIC OPTION WHEN

PHARMACOTHERAPY IS INEFFECTIVE IN CHILDREN WITH NOCTURNAL ENURESIS IN ASSOCIATION WITH DAY TIME INCONTINENCE? Ozkurkcugil C, Oney E, Dursun E, Gokalp A

16:30 57 LONG-TERM OUTCOMES OF LOWER URINARY TRACT FUNCTION IN PATIENTS WITH

OCCULT SPINAL DYSRAPHISM:CAN EARLY NEUROSURGERY PROMISE BETTER OUTCOMES IN THE LONG-TERM ? Kakizaki H, Tanaka H, Shibata T, Moriya K, Furuno T, Mitsui T, Koyanagi T

16:45 58 INDIRECT RADIONUCLIDE CYSTOGRAPHY VOIDING PATTERNS IN CHILDREN WITH

PRIMARY VESICOURETERAL REFLUX: COMPARATIVE STUDY Vlajkovic M, Petronijevic V, Golubovic E, Ilic S, Rajic M , Bogicevic M

Wednesday 8th October 2003 09:00 – 10:30 Podium Session 3 LUTS 09:00 59 SYMPTOMS AND BOTHER OF FEMALE PATIENTS PRESENTING WITH LUTS IN

UROLOGY CENTRES IN ITALY: FIRST EVALUATION FROM THE FLOW STUDY Pesce F, Prezioso D , Zattoni F , Artibani W , Tubaro A , Scarpa R M, Rizzi C A

09:15 60 FEMALE URINARY INCONTINENCE - RUNNING IN THE FAMILY?

Hannestad Y, Lie R T, Rortveit G, Hunskaar S 09:30 61 HOW BOTHERSOME ARE LUTS DURING PREGNANCY?

van Brummen H J, Heintz P, van der Vaart H 09:45 62 GENDER DIFFERENCES IN 24-HOUR URINARY DIARIES OF ASYMPTOMATIC ADULTS.

Mueller E , Latini J , Lux M, Stablein U , Brubaker L, Kreder K , FitzGerald M P 10:00 63 PREVALENCE AND CORRELATES OF NOCTURIA IN MEN - A LARGE COMMUNITY

BASED STUDY Seim A, Hoyo C, Ostbye T , Vatten L

10:15 64 CORRELATION OF NON-INVASIVE URODYNAMICS WITH IPSS AND PROSTATE VOLUME

Huang Foen Chung J W N C, van Mastrigt R 11:30 - 13:00 Poster Session 5 Bladder Dysfunction 11:30 65 CEREBRAL CONTROL OF BLADDER FUNCTION: THE BRAIN-BLADDER CONNECTION

Griffiths D, Derbyshire S , Logue E , Stenger V A , Resnick N 11:37 66 URGE INCONTINENCE AS A PREDICTOR OF INSTITUTIONALIZATION IN AN OLDER

POPULATION Nuotio M, Tammela T L, Luukkaala T, Jylhä M

11:45 67 CORRELATION BETWEEN DETRUSOR AFTER-CONTRACTION AND OVERACTIVE

BLADDER SYNDROME, DETRUSOR OVERACTIVITY AND POST-MICTURITION DRIBBLE D'amico A, Pesce F, Rubilotta E, Sarti A, Curti P, Artibani W

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11:52 68 THE DIURNAL RHYTHM OF URINE OUTPUT AND AVP SECRETION IN ELDERLY NOCTURNAL POLYURICS, ELDERLY AND YOUNG CONTROLS. Hvistendahl G M, Frøkiær J, Nielsen S, Djurhuus J C

12:00 69 IDIOPATHIC DETRUSOR OVERACTIVITY IN WOMEN - A 5-10 YEAR LONGITUDINAL

STUDY OF OUTCOMES Morris A R, Westbrook J I, Moore K H

12:07 70 DOES DETRUSOR OVERACTIVITY EVER CEASE? REPEAT URODYNAMIC TESTING AT 1

TO 9 YEARS. Blackwell A L, Moore K H

12:15 71 AUTONOMIC RESPONSE TO STRESS IN INTERSTITIAL CYSTITIS

Lutgendorf S, Rothrock N, Hoffmann A, Zimmerman B, Latini J, Kreder K 12:22 72 HYPERBARIC OXYGEN FOR TREATMENT OF INTERSTITIAL CYSTITIS: RESULTS OF A

PILOT STUDY van Ophoven A, Rossbach G, Oberpenning F, Hertle L

12:30 73 CONTINUOUS INTRAVESICAL INFUSION OF RESINIFERATOXIN BY IN SITU DRUG

DELIVERY SYSTEM TO TREAT INTERSTITIAL CYSTITIS: A PILOT STUDY. Lazzeri M, Beneforeti P, Turini D, Spinelli M, Malaguti S, Giardiello G

12:37 74 CAN MEDICATION PROLONG WARNING TIME?

Cardozo L, Prescott K, Serdarevic D, Skillern L 12:45 75 EVALUATION OF OAB TREATMENT AND PATIENT SATISFACTION REFLECTING ‘REAL-

LIFE CONDITIONS’ IN UROLOGICAL OFFICES IN AUSTRIA Madersbacher H, Berner L, Struhal G, Eisenmenger M, Neumann M

12:52 76 CHRONIC SACRAL (S3) NERVE STIMULATION: THE EFFECTS ON NOCTURIA AND

NOCTURNAL BLADDER CAPACITY AND CORRELATES WITH SUPINE URODYNAMICS IN WOMEN WITH REFRACTORY URGE URINARY INCONTINENCE Bosch R, Groen J

11:30 - 13:00 Poster Session 6 Treatment of Incontinence 11:30 77 THE RISE AND DEMISE OF THE VESICA PROCEEDURE - LESSONS TO BE LEARNT

ABOUT BLADDER NECK SUSPENSION Reid S V, Parys B T

11:37 78 THE SAFETY, EFFICACY, COMFORT, AND PATIENT SATISFACTION WITH THREE

COMMONLY USED PENILE COMPRESSION DEVICES FOR MALE INCONTINENCE. Moore K N

11:45 79 URODYNAMIC FINDINGS AFTER RADICAL RETROPUBIC PROSTATECTOMY USING

SUSPENSION TECHNIQUE FOR RAPID RECOVERY OF CONTINENCE Noguchi M , Shimada A, Ogata H, Noda S

11:52 80 PELVIC RADIOTHERAPY DOES NOT INCREASE THE COMPLICATION RATES OF

ARTIFICIAL URINARY SPHINCTER IMPLANTATION Lai H H, Smith C P, Teh B S , Butler E B, Boone T B

12:00 81 PADS AND PRESSURE: AN INVESTIGATION INTO THE EFFECTS OF ABSORBENT

INCONTINENCE PADS ON PRESSURE MANAGEMENT MATTRESSES Fader M, Bain D, Cottenden A

12:07 82 PRODUCT FOCUS: DISPOSABLE PADS FOR WOMEN WITH LIGHT INCONTINENCE

MAKING THE RIGHT PRODUCT CHOICE. Clarke-O'Neill S , Pettersson L , Mandy F, Cottenden A , Brooks R

12:15 83 THE EFFECT OF PRIOR TREATMENT EXPERIENCE AND INCONTINENCE SEVERITY ON

THE PLACEBO RESPONSE OF STRESS URINARY INCONTINENCE (SUI) Yalcin I, Bump R

12:22 84 DULOXETINE VS. PLACEBO IN THE TREATMENT OF STRESS URINARY

INCONTINENCE: A GLOBAL PHASE 3 STUDY Millard R , Moore K, Yalcin I , Bump R

12:30 85 DOES THE SEVERITY OF STRESS INCONTINENCE INFLUENCE OUTCOME FOLLOWING

TVT ? Karantanis E, Tate S, Wang K, Fynes M, Stanton S

12:37 86 A RANDOMISED CONTROL TRIAL OF TENSION-FREE VAGINAL TAPE IN COMPARISON WITH PUBOVAGINAL SLING IN THE TREATMENT OF STRESS INCONTINENCE Kondo A, Kimura K, Isobe Y , Kamihira O , Matsuura O

12:45 87 LAPAROSCOPIC BURCH COLPOSUSPENSION VERSUS THE TENSION-FREE VAGINAL

TAPE PROCEDURE: A RANDOMIZED CLINICAL TRIAL Paraiso M F, Walters M, Karram M, Barber M

12:52 88 SURGERY OF FEMALE URINARY INCONTINENCE USING TRANS-OBTURATOR TAPE

(TOT) : A PROSPECTIVE RANDOMISED COMPARATIVE STUDY WITH TVT. Mansoor A, Védrine N, Darcq C

14:00 - 15:30 Poster Session 7 Neurourology 14:00 89 A PET STUDY TO ASSESS SUPRASPINAL RESPONSE TO SACRAL

NEUROMODULATION IN WOMEN WITH URINARY RETENTION DasGupta R, Critchley H, Dolan R, Fowler C

14:07 90 BRAIN PLASTICITY AND URGE INCONTINENCE: PET STUDIES DURING THE FIRST

HOURS OF SACRAL NEUROMODULATION Blok B, Groen J, Veltman D, Bosch R, Lammertsma A

14:15 91 HAEMODYNAMICS CHANGES DURING BLADDER FILLING AND MICTURITION IN

NORMAL VOLUNTEERS Siracusano S, Cucchi A, Di Benedetto P, d'Aloia G , Knez R, Ciciliato S, Carretta R, Belgrano E

14:22 92 EFFECT OF NOCTURNAL URINARY DRAINAGE FOR TREATMENT OF BLADDER

DETERIORATION IN PATIENTS OF NEUROPATHIC BLADDER DYSFUNCTION Taniguchi N, Numata A, Kaneko S, Yachiku S, Mizunaga M

14:30 93 COMBINATION OF A CHOLINERGIC DRUG AND AN ALPHA-BLOCKER IS MORE

EFFECTIVE THAN MONOTHERAPY FOR THE TREATMENT OF VOIDING DIFFICULTY IN PATIENTS WITH UNDERACTIVE DETRUSOR Yamanishi T, Furuya N, Yasuda K , Sakakibara R, Uchiyama T, Hattori T, Kamai T, Tsujii T, Yoshida K

14:37 94 ORAL NITRIC OXIDE DONORS - A NEW PHARMACOLOGICAL APPROACH TO

DETRUSOR-SPHINCTER DYSSYNERGIA IN SPINAL CORD INJURED PATIENTS? Reitz A, Knapp P A , Müntener M, Schurch B

14:45 95 INTRAVESICAL RESINIFERATOXIN VERSUS BOTULINUM-A TOXIN INJECTIONS FOR

THE TREATMENT OF NEUROGENIC DETRUSOR OVERACTIVITY Giannantoni A, Di Stasi S M, Pizzirusso G, Mearini E, Bini V, Porena M

14:52 96 ENGLISH BOTULINUM TOXIN-A IN THE TREATMENT OF NEUROGENIC DETRUSOR

OVERACTIVITY Del Popolo G, Li Marzi V, Panariello G, Lombardi G

15:00 97 ARE BOTULINUM-A TOXIN INJECTIONS INTO THE DETRUSOR OF PATIENTS WITH

NEUROGENIC DETRUSOR OVERACTIVITY SAFE? ULTRASTRUCTURAL DATA OF DETRUSOR BIOPSIES. Haferkamp A, Krengel U , Reitz A, Grosse J, Kramer G, Schumacher S, Schurch B, Stöhrer M, Müller S C

15:07 98 CHRONIC PUDENDAL NERVE ELECTROSTIMULATION: FIRST EXPERIENCE OF THE

NEW PERCUTANEOUS IMPLANT WITH NEUROPHYSIOLOGICAL GUIDANCE Spinelli M, Malaguti S, Giardiello G, Lazzeri M, Van den Hombergh U, Gerber M

15:15 99 VARIATION IN THE UROLOGICAL MANAGEMENT OF SPINAL CORD INJURY PATIENTS

IN THE UK AND EIRE Bycroft J, Bywater H, Knight S, Hamid R, Shah J, Craggs M

15:22 100 DEFECATORY FUNCTION IN MULTIPLE SYSTEM ATROPHY; A COLONIC TRANSIT TIME

AND VIDEOMANOMETRY STUDY Sakakibara R, Odaka T, Uchiyama T, Asahina M, Yamanishi T, Hattori T

14:00 - 15:30 Poster Session 8 Pelvic Floor 14:00 101 IS INCREASED COLLAGEN METABOLISM THE CAUSE OR EFFECT OF PROLAPSE?: A

CONTROLLED STUDY Laborda E, Gelman W, Anthony F, Monga A

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14:07 102 URETHRAL FUNCTION FOLLOWING VAGINAL OR CAESAREAN DELIVERY. Chaliha C , Khullar V, Sultan A, Monga A, Stanton S L

14:15 103 ASSOCIATION OF THE MAGNITUDE OF PELVIC ORGAN PROLAPSE AND PRESENCE

AND SEVERITY OF SYMPTOMS Barber M, Walters M, Bump R

14:22 104 PELVIC RELAXATION IN NULLIPAROUS POSTMENOPAUSAL WOMEN AND THEIR

PAROUS SISTERS. Buchsbaum G, Kerr L, Guzick D

14:30 105 PUBOCOCCYGEAL MUSCLE INTEGRITY AND URETHRAL CLOSURE PRESSURES

DURING VOLITIONAL PELVIC FLOOR MUSCLE CONTRACTION IN WOMEN WITHOUT STRESS INCONTINENCE OR PELVIC ORGAN PROLAPSE Miller J M, Umek W H, DeLancey J, Ashton-Miller J A

14:37 106 STRESS URINARY INCONTINENCE, URETHRAL SUPPORT, AND URETHRAL FUNCTION

AMONG WOMEN WITH PELVIC ORGAN PROLAPSE ANALYZED BY PROLAPSE TYPE Morgan D, Fenner D, Wolfgang U, Guire K , DeLancey J

14:45 107 SEVERITY OF PELVIC ORGAN PROLAPSE IS ASSOCIATED WITH MEASUREMENTS OF

GENITAL HIATUS Ghetti C, Gregory T, Edwards R, Clark A

14:52 108 DYNAMOMETRIC EVALUATION OF PELVIC FLOOR MUSCLES FUNCTION IN CONTINENT

AND STRESS URINARY INCONTINENT WOMEN Morin M, Dumoulin C, Bourbonnais D, Lemieux M, Gravel D

15:00 109 LONG TERM EVALUATION OF THE TISSUE RESPONSE AND MECHANICAL

PROPERTIES OF TWO COLLAGEN BASED AND POLYPROPYLENE IMPLANTS IN A RABBIT MODEL FOR ABDOMINAL WALL REPAIR . Claerhout F, Deprest J, Zheng F, Konstantinovic M, Lagae P, De Ridder D

15:07 110 IS THE EFFICACY OF PELVIC FLOOR MUSCLE REHABILITATION FOR URINARY STRESS

INCONTINENCE AGE-RELATED? A REVISION OF 170 WOMEN Canepa G, Garaventa M, Parodi M, Steardo L, Satta P, Maffenzzini M

15:15 111 SINGLE BLIND, RANDOMIZED TRIAL OF PELVIC FLOOR MUSCLE TRAINING (PFMT),

BIOFEEDBACK ASSISSTED PELVIC FLOOR MUSCLE TRAINING (BAPFMT) AND ELECTRICAL STIMULATION (ES) IN THE MANAGEMENT OF OVERACTIVE BLADDER (OAB) Wang A, Wang Y

15:22 112 LONG-TERM ANATOMIC RESULTS OF DISCRETE SITE-SPECIFIC DEFECT REPAIR

VERSUS TRADITIONAL POSTERIOR COLPORRHAPHY FOR THE CORRECTION OF ADVANCED RECTOCELE: A 1 YEAR FOLLOW-UP ANALYSIS Abramov Y, Kwon C, Gandhi S, Goldberg R, Sand P

16:00 - 17:00 Podium Session 4 Treatment of Incontinence 16:00 113 WOMEN’S PREFERENCES FOR TREATMENT FOR STRESS INCONTINENCE-

PHYSIOTHERAPY OR SURGERY Karantanis E, Stanton S, Parsons M, Robinson D, Blackwell A L, Cardozo L, Moore K

16:15 114 DULOXETINE TREATMENT OF WOMEN WITH ONLY URODYNAMIC STRESS

INCONTINENCE AWAITING CONTINENCE SURGERY Drutz H, Cardozo L, Baygani S , Bump R

16:30 115 THE TENSION-FREE VAGINAL TAPE OPERATION: RESULTS OF A REGISTRY

Tamussino K, Hanzal E, Kölle D, Ralph G, Riss P 16:45 116 SAFETY AND EFFICACY OF THE TRANS OBTURATOR TAPE IN THE TREATMENT OF

STRESS URINARY INCONTINENCE Kocjancic E, Costa P , Wagner L, Crivellaro S, Gherzi R, Gontero P, Favro M, Ceratti G, Tarrano E, Sala M, Frea B

Thursday 9th October 2003 09:00 - 10:30 Podium Session 5 Overactive Bladder 09:00 117 MUSCARINIC RECEPTOR BINDING IN HUMAN DETRUSOR - AGE RELATED CHANGES

Mansfield K, Mitchelson F, Moore K, Burcher E

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09:15 118 IMPACT OF URGE INCONTINENCE SEVERITY ON DRUG TREATMENT EFFICACY Landis J R, Kaplan S, Swift S, Versi E

09:30 119 PSYCHOMETRIC VALIDATION OF AN URGENCY SEVERITY SCALE (IUSS) FOR

PATIENTS WITH OVERACTIVE BLADDER. Bowden A, Colman S, Sabounjian L , Sandage B , Schwiderski U , Zayed H

09:45 120 THE EFFICACY, EFFECTIVENESS, AND SAFETY OF TRANSDERMAL OXYBUTYNIN IN

PATIENTS WITH OVERACTIVE BLADDER Dmochowski R, Staskin D, Appell R, Zinner N, Gittelman M, Davila G, Sand P

10:00 121 RESULTS OF A RANDOMIZED PHASE 3 STUDY COMPARING SOLIFENACIN SUCCINATE

WITH TOLTERODINE AND PLACEBO IN PATIENTS WITH SYMPTOMATIC OVERACTIVE BLADDER Chapple C, Rechberger T, Al-Shukri S, Meffan P , Everaert K, Ridder A

10:15 122 DOES ANTI-MUSCARINIC THEARAPY EXACERBATE VOIDING DIFFICULTIES?

Robinson D, Dixon A , Cardozo L, Anders K , Balmforth J, Parsons M 14:15 - 16:15 Podium Session 6 Pelvic Floor 14:15 123 PELVIC FLOOR SOFT TISSUE STRETCH INDUCED BY VAGINAL BIRTH

Ashton-Miller J A, Lien K, DeLancey J 14:30 124 URINARY INCONTINENCE DURING PREGNANCY PREDICTS POSTPARTUM UI MORE

EFFECTIVELY THAN TYPE OF DELIVERY (CESAREAN VS. VAGINAL) Sampselle C M, Miller J M

14:45 125 ASK NOT WHAT CHILDBIRTH CAN DO TO YOUR PELVIC FLOOR BUT WHAT YOUR

PELVIC FLOOR CAN DO IN CHILDBIRTH. Balmforth J, Toozs-Hobson P, Cardozo L

15:00 126 LEVATOR ANI MUSCLE STRUCTURE AND FUNCTION IN WOMEN WITH PROLAPSE

COMPARED TO WOMEN WITH NORMAL SUPPORT DeLancey J, Kearney R, Umek W, Ashton-Miller J A

15:15 127 CONSERVATIVE MANAGEMENT OF STRESS URINARY INCONTINENCE: A SINGLE-

BLIND, RANDOMIZED CONTROLLED TRIAL OF PELVIC FLOOR REHABILITATION WITH OR WITHOUT ABDOMINAL MUSCLE REHABILITATION COMPARED TO THE ABSENCE OF TREATMENT. Dumoulin C, Lemieux M , Bourbonnais D , Morin M

15:30 128 GROUP TEACHING OF PELVIC FLOOR AND BLADDER TRAINING: FUNCTION AND

KNOWLEDGE OUTCOMES Sampselle C M, Messer K L, Herzog R, Hines S J, Karl C , Diokno A A

15:45 129 PROSPECTIVE EVALUATION OF URETHRO-VESICAL, VULVO-VAGINAL AND ANO-

RECTAL FUNCTION AFTER TOTAL MESOMETRIAL RESECTION (TMMR) IN CERVICAL CANCER Naumann G, Hentschel B, Höckel S, Höckel M

16:00 130 TRANSANAL OR VAGINAL APPROACH TO RECTOCELE REPAIR: RESULTS OF A

PROSPECTIVE RANDOMISED STUDY Nieminen K, Hiltunen K, Laitinen J, Oksala J, Heinonen P

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1 Herbison G P1 1. Otago University THE REPORTING QUALITY OF ABSTRACTS OF RANDOMISED CONTROLLED TRIALS SUBMITTED TO THE ICS MEETING IN HEIDELBERG Aims of Study The quality of randomised controlled trials(RCTs) is associated with bias(1,2). Thus reports of RCTs must have enough detail of key elements of quality to enable them to be interpreted properly. A group of editors of major medical journals sponsored a group to come up with guidelines for the reporting of RCTs, called the CONSORT statement(3). Details of this and other reporting quality guidelines are on the internet at http://www.consort-statement.org/. This study examines the quality of abstracts of RCTs reported at the ICS meeting in Heidelberg in 2002. Methods All of the abstracts accepted for the meeting at Heidelberg were read to identify reports of RCTs. Copies of these were then printed and examined to see whether they complied with the 22 items in the CONSORT statement. As these were all abstracts the first item was changed so that to comply the title had to say it was a randomised trial. Each item was scored as not met, partially met, met. Results Fifty-three reports of randomised controlled trials were found. 5 of these were podium presentations, 14 discussion posters, and 34 non-discusion posters. Compliance with the CONSORT items is given in the table. CONSORT ITEM No. Description

Not met Partially met

Met

1 How participants were allocated to interventions (eg. "random allocation" or "randomly assigned")

30 (57%) 3 (5.7%) 19 (38%)

2 Scientific background and explanation of rationale 9 (17%) 17 (32%) 27 (51%) 3 Eligibility criteria for participants and the settings and locations

where the data were collected 5 (9%) 28 (53%) 20 (38%)

4 Precise details of the interventions intended for each group and how and when they were actually administered

2 (4%) 18 (34%) 33 (62%)

5 Specific objectives and hypotheses 5 (9%) 21 (40%) 27 (51%) 6 Clearly defined primary and secondary outcome measures

and, when applicable, any methods used to enhance the quality of measurement (eg. multiple observations, training of assessor, &c)

6 (11%) 24 (45%) 23 (43%)

7 How sample size was determined and, when applicable, explanation of any interim analyses and stopping rules

50 (94%) 1 (2%) 2 (4%)

8 Method used to generate the random allocation sequences, including details of any restriction (eg. blocking, stratification)

47 (89%) 5 (9%) 1 (2%)

9 Method used to implement the random allocation sequence (eg. numbered containers or central telephone), clarifying whether the sequence was concealed until investigations were assigned

50 (94%) 2 (4%) 1 (2%)

10 Who generated the allocation sequence, who enrolled participants, and who assigned the participants to their groups

52 (98%) 0 (0%) 1 (2%)

11 Whether or not the participants, those administering the interventions, and those assessing the… outcomes were aware of group assignment. If not, how the success of masking was assessed.

23 (43%) 9 (17%) 21 (40%)

12 Statistical methods used to compare groups for primary outcome(s); methods for additional analyses, such as subgroup analyses and adjusted analyses

30 (57%) 7 (13%) 16 (30%)

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13 Flow of participants through each stage (a diagram is strongly recommended). Specifically for each group, report the numbers of participants randomly assigned, receiving intended treatment, completing the study protocol, and analysed for the primary outcome. Describe protocol deviations from study as planned together with the reasons

12 (23%) 17 (32%) 23 (45%)

14 Dates defining the periods of recruitment and follow-up 48 (91%) 0 (0%) 5 (9%) 15 Baseline demographic and clinical characteristics of each

group 39 (74%) 9 (17%) 5 (9%)

16 Number of participants (denominator) in each group included in each analysis and whether the analysis was by "intention to treat". State the results in absolute numbers when feasible (eg. 10/20, not 50%)

14 (26%) 27 (51%) 2 (4%)

17 For each primary and secondary outcome, a summary of results for each group, and the estimated effect size and its precision (eg, 95% CI)

24 (45%) 27 (51%) 2 (4%)

18 Address multiplicity by reporting any other analyses performed, including subgroup analyses and adjusted analyses, indicating those prespecified and those exploratory

13 (25%) 25 (47%) 15 (28%)

19 All important adverse events or side-effects in each intervention group

17 (32%) 10 (19%) 26 (49%)

20 Interpretation of results, taking into account study hypotheses, sources of potential bias or imprecision and the dangers associated with multiplicity of analyses and outcomes

0 (0%) 16 (30%) 37 (70%)

21 Generalisability (external validity) of the trial findings 38 (72%) 9 (17%) 6 (11%) 22 General interpretation of the results in the context of current

evidence 26 (49%) 22 (42%) 5 (9%)

Only 2/53 (4%) of the abstracts complied fully with more than 10 of the items, and 30/53 (57%) did not comply at all with 10 or more. Conclusions The quality of reporting of studies at ICS is so poor that it is difficult to interpret the results. Reporting was particularly poor on the details of the randomisation and the numeric results. 1. Egger M, Ebrahim S, Davey Smith G. Where now for meta-analysis? International Journal of

Epidemiology 2002;31:1–5. 2. Schulz KF, Chalmers I, Hayes RJ, Altman DG. Empirical evidence of bias. Dimensions of

methodological quality associated with estimates of treatment effects in controlled trials. JAMA 1995;273:408–412.

3. Altman DG, Schulz KF, Moher D, Egger M, Davidoff F, Elbourne D, et al. The revised CONSORT statement for reporting randomized trials: explanation and elaboration. Annals of Internal Medicine 2001;132:663-94.

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2 Griffiths C1, Blake C2, Harding C3, McIntosh S3, Drinnan M1, Robson W3, Pickard R3, Abrams P2, Ramsden P3 1. Regional Medical Physics Department, 2. Bristol Urological Institute, 3. Urology Department, Freeman Hospital, Newcastle upon Tyne, UK NON-INVASIVE BLADDER PRESSURE: THE CASE FOR USING A MODIFIED ICS NOMOGRAM Aims of Study The ICS nomogram classifies patients as obstructed (O), equivocal (E) or unobstructed (U) using maximum flow (Qmax) and detrusor pressure at maximum flow (pdet,Qmax) from an invasive pressure flow study (PFS) (1). The penile-cuff pressure required to interrupt flow (pcuff,int) provides a non-invasive estimate of isovolumetric bladder pressure (pves,isv) (2). This paper considers the expected relationship between pcuff,int (or pves,isv) and pdet,Qmax and the modification required to the ICS nomogram to produce a nomogram for the cuff test. Non-invasive data from 2 large urology departments were used to assess the modified nomogram. Methods On the ICS nomogram, the line separating obstructed from equivocal (O/E line) passes through 40 cm water at zero flow and has a slope of 2xQmax. Previously reported results (see below) suggest two possible adjustments for non-invasive data: offset and slope. Step 1(Offset): The cuff test estimates bladder pressure (pves), which includes abdominal pressure and also a small component due to the height difference between the cuff and bladder. The mean (+ SD) abdominal pressure during voiding and height difference were measured in patients with lower urinary tract symptoms to estimate the correction required. Step 2 (Slope): The non-invasive technique measures pves,isv, flow being zero at the time of measurement. pves,isv is expected to be higher than pves at full flow, by an amount dependent on the flow rate (Q) prior to interruption. The slope of the O/E line should be increased to allow for this. The pressure increase was plotted against pre-interruption flow rate in patients undergoing cuff test plus PFS in order to estimate the required correction. Step 3 (Modified Nomogram ): Using the results from steps 1 and 2, a modified nomogram was proposed. Step 4 (Patient data): Data was collected using an identical non-invasive technique from 2 UK urology departments. Patients underwent a cuff test and, on a separate occasion, invasive PFS. From the cuff test, pcuff,int and Qmax (excluding surges after cuff release) were estimated for each patient and plotted on the proposed nomogram. The symbol used indicated their classification from their separate invasive PFS. Results Step 1: The mean (+ SD) abdominal pressure during voiding for 76 patients was 35 (+9) cm water (3). With the measured height difference of 8.8 (+ 1.4) cm, the O/E line should be offset approximately 40 cm, giving an intercept of 80 cm water. Step 2: Figure 1 illustrates the pressure rise to pves,isv as a function of pre-interruption flow rate for 13 subjects ( 64 inflation cycles). There is variability between individuals, but the average pressure rise is approximately 2 times the flow rate (4).

Fig 1. Pressure increase v flow rate

-50

0

50

100

0 5 10 15 20Pre-interruption Q (mL/s)

p det

,isv-p

det,

pre (

cm H

20)

VolunteersPatientsmean

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Step 3: Figure 2 illustrates the development of the modified nomogram using the results from steps 1 and 2. The total slope after applying step 2 is 4xQ.

Step 4: Figure 3 illustrates the non-invasive data plotted on the modified nomogram for 57 and 86 patients from the two centres, with indication of their ICS classification from the separate invasive PFS (•=O, ∆=E, ∼=U).

Fig 3. Combined data provisional nomogram (n=143)

0

50

100

150

200

0 5 10 15 20 25 30Cuff test Qmax (ml/s)

Hig

hest

pcu

ff.in

t (cm

H2O

)

obstructed (n=52)equivocal (n=44)unobstructed (n=47)

Conclusions A rationale and supporting data have been provided for a modified ICS nomogram which could be used for non-invasive data recorded with the cuff interruption technique. The separation of patients classified invasively looks encouraging but further refinement may be required. The technique may provide useful, objective data intermediate between flow rate alone and full PFS for men with LUTS. References (1) Neurourol & Urodyn 16: 1-18 (1997) (2) J Urol 167: 1344 – 1347 (2002) (3) Neurourol & Urodyn (In press) (4) Neurourol & Urodyn 20: 382-384 (2001)

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3 Harding C1, Mcintosh S1, Robson W1, Ramsden P1, Drinnan M1, Griffiths C1, Pickard R1 1. Freeman Hospital VALIDATION OF THE PENILE COMPRESSION-RELEASE MANOEUVRE FOR NON-INVASIVE DIAGNOSIS OF BLADDER OUTFLOW OBSTRUCTION Aims of Study The invasive nature of conventional cystometry has encouraged the development of alternative urodynamic techniques that do not require bladder catheterisation. Most non-invasive methods rely on flow interuption during voiding to allow an estimate of isovolumetric bladder pressure. The currently available methods include mechanical interuption at the external meatus using a condom catheter (1), interruption at the level of the penile urethra using an inflatable cuff (2) and manual compression and release of the penile urethra during voiding (3). All of these measures seek to differentiate between the urodynamic diagnoses of bladder outlet obstruction (BOO), detrusor hypocontractility (DH) and detrusor overactivity (DO). The present study aimed to validate the penile compression-release manoeuvre described by Sullivan and Yalla (2000) by repeating their study using mechanical interuption of flow with a penile cuff rather than manual compression. Methods One hundred and fifty men with lower urinary tract symptoms (LUTS) attending for conventional and non-invasive pressure-flow studies (PFS) were included in this study. Invasive data were collected and used to classify men into the diagnostic groups of Normal (NOR), Bladder outlet obstruction (BOO), Detrusor Hypocontractility (DH) and Detrusor Overactivity (DO). A flexible plastic cuff was placed around the penis and inflated during micturition until flow was interrupted. After flow interruption the cuff was deflated automatically and voiding resumed. This cycle was then repeated throughout the course of the void (Fig 1). The PCR index was then calculated using maximum flow obtained post-compression (Qsurge) and the quasi-steady state flow rate (Qss): PCR INDEX (%) = (Qsurge – Qss) / Qss x 100

Qss

Qsurge

Fig 1 Penile compression-release manoeuvre by automated inflation of a penile cuff The mean PCR index (%) was calculated for each patient and the results analysed for each urodynamic group and compared by variance analysis. A receiver-operator characteristics curve (ROC) was constructed to define PCR index threshold above which prediction of BOO was optimised.

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Results Forty-nine subjects were excluded because of low voided volume, no arrest or return of voiding, lack of comparible PFS data or technical failure leaving one hundred and one data sets for analysis.The table below shows the data obtained:

GROUP NUMBER MEAN PCR INDEX (%)

STANDARD DEVIATION P VALUE (cf. NOR)

BOO 28 213 84.3 <0.0001 DO 19 151.3 87 0.027 NOR 16 97.8 38.7 ------- DH 38 102.5 54.5 0.73

Table 1 PCR indices for different urodynamic groups A variance analysis was initially applied to all of the four groups which showed a significant difference (p<0.00001). Each diagnostic group was then compared to the normal group using Student’s t-test and the p-values tabulated above. These results show a significantly higher mean PCR index in the obstructed (BOO) and the DO groups. The predictive value of the PCR index was examined by plotting a receiver-operator characteristics curve defining obstruction as a positive result.

Fig 2 The ROC curve suggests that a PCR index of 160% is the optimum threshold above which BOO can be diagnosed with sensitivity of 0.81, specificity of 0.84 and positive predictive value of 69%. Conclusions This study confirms that the PCR index shows promise as a simple, reliable and non-invasive method of evaluating men with LUTS. The surge in urine flow that occurs following release of penile urethral compression is thought to represent the action of isovolumetric bladder pressure on the reservoir of urine contained within the compliant anterior urethra. Thus the PCR index expresses pressure flow data for each void. In the present study the significantly higher PCR index in the obstructed group is likely to represent higher isovolumetric bladder pressure and lower flow rate. It does not appear to be affected by the presence of detrusor overactivity. Our threshold value for PCR index of 160% above which BOO could be diagnosed was higher than that of 100% set by Sullivan and Yalla (2000). This may represent an advantage of automated penile compression which has been shown not to inhibit detrusor contraction. Further comparitive studies are required to determine how the PCR index compares with other non-invasive measures of voiding function in predicting the presence of BOO and the response to treatment. Reference 1 BJU Int 1999;84:195-203 2 J Urol 2002;167:1344-7 3 NeuroUrol. Urodyn 2000;19:657-669

PCR Index threshold for Obstruction

00.20.40.60.8

1

0 0.2 0.4 0.6 0.8 11-specificity

sens

itivi

ty

160

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4 Bruschini H1, Almeida F1, Srougi M 1 1. Universidade Federal de Sao Paulo IS THERE A ROLE FOR URODYNAMIC TEST ON CONSERVATIVE TREATMENT? URODYNAMIC EVALUATION OF URINARY INCONTINENT WOMEN TREATED WITH PERINEAL MAGNETIC STIMULATION. Aims of Study The perineal magnetic stimulation (PMS) arose as an alternative to electrical perineal stimulation on the urinary incontinence treatment. The perineal electrical stimulation has been proved to be effective and safe, however the vaginal and anal electrodes causing pain and discomfort has been a great obstacle to a wide use. The PMS generates a magnetic field, which is able to stimulate deep nerves with no significant interference by the body tissues. On the other words, PMS generates the same or a better stimulation on the pelvic floor nerves than electrical stimulation, does not need electrodes or direct skin contact, is painless and does not need training. The role of urodynamic study (UDS) in conservative treatment is controversial, because the test can be more invasive than the treatment itself. The UDS would be justifiable only if it could add any advantage to the treatment by means of better patient selection. We evaluate the effect of 16 sessions of PMS on clinical and urodynamic parameters and the UDS potential benefit on the PMS pre-treatment evaluation. Methods Forty one consecutive outpatients’ women were enrolled in a prospective clinical trial. Eligible patients were neurologically normal, had normal urinalysis, absence of severe prolapse and demonstrable urinary incontinence (UI). All patients were treated using a specially designed chair (Neotonus Inc., Marieta, GA ). The PMS were done twice a week consisting 20 minutes of stimulation, being 10 minutes at 5 Hz and 10 minutes at 50 Hz. The evaluation was done through clinical history, symptom questionnaire, 72 hours voiding diary, validate quality of live questionnaire (I-QOL) and complete urodynamic test at baseline and after 16 sessions of PMS. Results The mean age was 62.5 + 10.3 years, 9 patients (22%) had previous hysterectomy, 20 patients (49.8%) had previous surgeries for UI treatment, 37 patients (90%) were post menopause and the mean body mass index (BMI) was 25.4 + 8, the initial clinical evaluation and urodynamic test showed 24 women (58.5%) with pure SUI and 17 (41.5%) patients with detrusor overactivity. Patients with detrusor overactivity were divided in two groups: 1) SUI associate with low pressure (< 15 cm H2O) detrusor overactivity (n=9) and 2) high pressure (> 15 cm H2O) detrusor overactivity leading to urinary leakage or involuntary voiding (n=8). Overall after 16 PMS sessions, the average improvement on the I-QOL score was 29.6% (p<0.001), the number of leaks/day and the number of pads/day had a mean decreased of 47.2% (p<0.001) and 36.2% (p<0.001), respectively. The UDS parameters evaluation showed increased of 36% (p=0.024) on mean volume at first filling sensation, 17.7% (p=0.005) on mean volume at the normal voiding sensation and 3% (p=0.780) on maximal bladder cystometric capacity. The PMS also increased the mean VLPP value in 24.3% (p=0.001). Ten women (24.4%) did not show leakage episodes at the clinical and urodynamic evaluation. The baseline VLPP of those patients that became dry was 80 cm H2O in one, 90 cm H2O in two and more than 90 cm H2O in seven patients. Six (66%) out of 9 patients with low pressure detrusor overactivity became dry and 7 patients (77%) became free of urge/urge-incontinence symptoms and detrusor overactivity. On the other hand, no one out of the 8 patients with high pressure overactive bladder became dry or showed any change on bladder behaviour. Conclusions Overall, women with urinary incontinence treat by PMS have a significant improvement on the symptoms, VLPP and QOL, with 24% of objective chance to become dry. Patients with SUI associated to symptoms of urge or urge-incontinence and low pressure bladder overactivity have 66% chance to become dry and 77% chance to get rid of the overactivity. High pressure bladder overactivity does not respond to this approach. The treatment is more effective if the baseline VLPP is over than 80 cmH2O. Due to the ability to separate groups with high chance to get cure from groups with low chance of improvement, pre treatment UDS evaluation can beneficiate patients in conservative treatment.

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5 Cannon T1, Conway D1, Lu S H1, Xavier M1, Fraser M O1, Chermansky C1, de Groat W1, Huard J1, Chancellor M1 1. University of Pittsburgh LEAK POINT PRESSURE TESTING AFTER TISSUE ENGINEERED SLING PLACEMENT IN A MODEL OF STRESS URINARY INCONTINENCE Aims of Study The purpose of this study was to evaluate the functional effects of a tissue engineered sling in an animal model of stress urinary incontinence (SUI). There is very little treatment-oriented research utilizing tissue engineering techniques for SUI. Using such techniques, we propose to develop a truly physiologic sling, not from synthetic or cadaveric tissue, but rather an engineered sling that can be implanted to repair a damaged urethral sphincter. This abstract is the first step toward this goal. Methods Female rats were divided into four groups (n=5/group): a control group (C) had no pre-LPP interventions, a denervated group (D) that underwent bilateral PSNT and periurethral dissection without sling placement, a SIS sling group (S) that had concomitant bilateral PSNT and SIS suburethral sling placement, and finally the tissue engineered sling group (M) that underwent concomitant bilateral PSNT with implantation of a tissue engineered sling. Suburethral sling placement was performed via a transabdominal approach using a sling sutured to the pubic bone. Tissue engineered slings were prepared with muscle derived cells obtained via the preplate technique and subsequently seeded for 2 weeks on an SIS scaffold. Suburethral slings were implanted for two weeks prior to LPP testing using the verticle tilt/intravesical pressure clamp method (Fraser et al., 2000, J Urol., 163:76). Intravesical pressure was increased in 1-2 cm steps for ~30 seconds/step until visible leakage (LPP). The mean values of 3-4 trials were analyzed and data is presented as mean � SEM. Results LPPs from both sling groups (S and M) were not different than untreated controls (C). The S, M, and C groups all had significantly higher LPPs than PSNT alone animals (D). Importantly, no rat from either sling group (S and M) demonstrated signs of urinary retention.

LPP in cm H2O

C D S M

Mean 46.1 18.0 51.2 51.4

SEM 1.8 6.6 1.6 6.0 Conclusions Placement of tissue engineered slings in an animal model of SUI resulted in LPP measurements that were not significantly different from LPPs of the untreated control or SIS alone groups. These data demonstrate that the incorporation of stem cells into SIS slings does not adversely alter the mechanical advantage of sling placement in a stress urinary incontinence model, and therefore sets the stage for future functional studies of tissue engineering sling materials.

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6 Pajoncini C1, Costantini E1, Bini V1, Tascini M C1, Rociola W1, Guercini F1, Porena M1 1. Department of Urology, Perugia University VLPP AND SURGICAL OUTCOME: PRELIMINARY DATA Aims of Study More than 100 surgical approaches have been attempted to cure stress urinary incontinence (SUI) but despite recent advances in urodynamics assessment, there is still no consensus on the surgical choice. The Valsalva Leak Point Pressure (VLPP) has emerged has a major diagnostic test in evaluating SUI and quantifying incontinence. It is being used to predict outcome after surgery as patients with a low VLPP seem to have an increased risk of developing intrinsic sphincter deficiency post-operatively. This study was designed to relate pre-operative VLPP values to clinical outcome in women who underwent colposuspension and prolapse repair for SUI associated with severe pelvic organ prolapse. Methods 31 consecutive patients with stress or mixed urinary incontinence associated with severe uro-genital prolapse underwent retropubic colposuspension during sacrocolpopexy. All patients underwent a full urogynaecological work up which included case history, clinical examination with assessment of vaginal profile sec. Baden and Walker, multichannel cystometry with Pressure/Flow study, VLPP, Urethral Pressure Profile with Maximum Urethral Closure Pressure (MUCP). Preoperatively the VLPP was assessed after reducing pelvic prolapse with gauze packing and using the lower half of a vaginal speculum to support the vault and proximal anterior vaginal wall without causing urethral obstruction. The patient was in gynaecological position, the bladder was filled to a volume of 200 cc, a 7 Fr catheter was used. A remote control device recorded the bladder pressure exactly when urine appeared at the external urinary meatus. Positive VLPP was defined as the lowest of three increases in bladder pressure above rest pressure recorded at the time of leakage, in the absence of detrusor contractions. If there was no urinary leakage the VLPP was considered negative and the maximum bladder pressure achieved during the Valsalva maneuver was registered. A value of ≤ 60 cm H2O was chosen as cut-off for VLPP as suggested by McGuire. Surgical results were evaluated by a post-surgical stress test and subjective assessment (cured = no incontinence; improved = occasional incontinence or less severe incontinence; failed = no change or worsening of incontinence).

Statistical analysis Chi square test was used to compare VLPP and MUCP values with surgical outcome. On the basis of clinical outcome patients were divided into two groups: cured/improved or failed.. Failed patients were considered as having disease status = 1, and cured/improved patients disease status = 0. Disease status was considered the dependent variable and was correlated in logistic regression analysis against the independent variables: age, menopause, previous urogynaecological surgery and/or hysterectomy, Body Mass Index, grade of incontinence ≥ 2, overactive bladder, VLPP and MUCP. Results

Mean age of patients was 62 years with 26 (83.8%) in menopause. Mean BMI was 26, mean parity 2 and median daily pads was 1. Seven pts (22.5%) had incontinence ≥ grade 2,. Ten (32.2%) had undergone previous urogynaecological surgery and/or hysterectomy, 25 (80.6%) presented with cystocele ≥ grade 3 or vault prolapse. Six patients with cystocele < grade 3 presented with grade 3 hysterocele or rectocele. Twenty-four (77.4%) had obstructive symptoms. The mean follow up was 36 months (range 9 – 75). Chi square test shows VLPP and MUCP values, whether alone or combined, do not correlated with surgical failure (tab.1). Logistic regression analysis shows surgical

Failed VLPP ≤ 60 cm H2O (9paz.) 4 (44.4%) VLPP > 60 cm H2O (22 pts) 5 (22.7%) p NS MPCU ≤ 30 cm H2O (11pts) 5 (45.4%) MPCU > 30 cm H2O (20 pts.) 4 (20.0%) p NS VLPP<60cm e/o MPCU <30cm (15pts.) 7 (46.6%) VLPP>60cm e MPCU >30cm (16paz.) 2 (12.5%) p NS Tab.1 Chi square test

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failure is correlated with a high BMI (B = -0.363; p = 0.03) and with combined VLPP and/or MUCP low values (B = -3.05; p = 0.01). Conclusions Women with SUI and severe uro-genital prolapse have major abnormalities in pelvic statics with multiple defects in anterior, middle and posterior compartments. An accurate diagnosis is hard to achieve and these patients are at high risk of surgical failure. Although all our patients were affected by urinary incontinence, the incidence of obstructive symptoms was high and even with prolapse reduction urinary incontinence may be underestimated when obstruction is present. Even though there were relatively few patients in this series, our results show individual pre-operative VLPP values are not correlated with clinical outcome after colposuspension associated with urogenital prolapse repair. However, logistic regression analysis showed a discreet correlation between combined low VLPP and/or low MUCP and outcome, suggesting the association of the two tests may be integrative in diagnosis. References 1) McGuire EJ, Fitzpatrick CC, Wan J, Bloorn D, Sanvordenker J, Ritchey M Gormley EA. 1993. Clinical

assessment of urethral sphincter function. J Urol;15:1452-1454 7 Fry C1, Wu C1, Sui G1 1. Institute of Urology, London CELLULAR PROPERTIES OF HUMAN SUB-UROTHELIAL MYOFIBROBLASTS - THEIR ROLE IN BLADDER SENSATION Aims of Study The sensation of bladder fullness initiates the micturition reflex and alteration of its sensitivity may contribute to syndromes such as sensory urge and even bladder pain. Recently it has been shown that stretch of the urothelium releases ATP at the baso-lateral surface [1] and the purine is believed ultimately to excite sub-urothelial afferents. However, the intermediate steps in this process remain unclear. Recently a layer of sub-urothelial myofibroblasts have been identified that make intimate contacts with nerve endings [2] and express gap junction proteins [3] and raises the possibility that they form an electrical network of cells that act as an intermediary step in the sensation pathway. If so these cells should be electrically active and respond to ATP by generating excitatory responses. The cellular properties of these cells from human biopsy samples were therefore investigated to determine if they fulfilled these criteria. Methods Human bladder wall samples were obtained with Ethical Committee approval from patients undergoing either cystectomy or bladder augmentation. The urothelium was dissected from the underlying detrusor and digested at 37°C with a collagenase-based medium with constant stirring for 30 minutes. The tissue was partially disrupted into round urothelial cells and a layer of ovoid or spindle-shaped cells with or without dendrite-like structures. Experiments were performed at 37°C in a HCO3

-/CO2 buffered superfusate. Electrophysiological recordings were made with patch-type electrodes filled with a KCl/EGTA-based solution. Intracellular [Ca2+], [Ca2+]i was measured with the fluorochrome Fura-2, excited at 340/380 nm (50Hz switching) and fluorescence intensity recorded between 410-480 nm. Data are presented as means±s.d. Results Cell capacitance was 27±16pF (n=53). Membrane potential was recorded in 16 cells and was on average –63±13mV. However the membrane potential showed either small fluctuation potentials or spikes that peaked around about -35mV. Membrane resistance was estimated to be 8.5-9.0x104 .cm2 from either the time constant of the resting potential change to small depolarising or hyperpolarizing currents or from the slope of the steady-state current-voltage relationship. Under voltage-clamp small, transient inward currents were followed by sustained outward currents on depolarisation from a holding potential of –100mV. Inward

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current was abolished in Ca-free superfusate, peaked at about –10 mV (25±10pA) and was smaller at 0 mV as the larger outward current overlaid the inward component. Outward current showed outward-going rectification with spontaneous transient components, exhibited a reversal potential at about –80mV and was greatly attenuated by 30mM tetraeythlammonium chloride. 100 µM ATP generated after a delay transient inward currents when the membrane was clamped at –60 mV, similar to the average resting membrane potential. The maximum peak inward current was 23±17pA (n=6). Separate experiments showed that ATP also elicited a transient increase of intracellular [Ca2+]. 30µM ATP increased [Ca2+] from 90±60nM to a peak of 832±500nM (18 transients, 4 cells). ATP was also applied to several epithelial cells from the urothelium/sub-urothelium biopsy, but no Ca2+ transients were observed. Conclusions It is possible to isolate cells from the urothelial layer of the bladder identified as being distinct from epithelial cells: they were more spindle shaped, but were distinctive from smooth muscle cells by their small size and shape. Thus they are not contaminant smooth muscle cells from the underlying detrusor but represent a distinct urothelial/suburothelial cell population, previously identified as myofibroblasts. The cells had many characteristics of excitable cells: a resting membrane potential of about –60mV; regenerative spikes in many cells; inward current followed by outward current; and inward current generated on application of an agonist. Thus these cells could form an electrical network that would distribute an electrical signal over a reasonable area upon focal depolarisation, which would be facilitated by the relatively high membrane resistance. The Ca-dependence and range of potentials over which inward current was generated imply that it is in part at least a Ca2+-current. The characteristics of the outward current suggest that a significant fraction is a Ca2+-dependent outward current, possibly through BK channels. These cells responded to ATP by inward current generation and a rise of intracellular [Ca2+]. The inward current is consistent with the presence of P2X purinoceptors. These properties are consistent with the hypothesis that these cells form an intermediate stage in the modality of bladder sensation and could act as a variable gain integrating stage. Thus their further study is important to understand how bladder sensation may be modulated.

References 1. Ferguson DR, Kennedy I, Burton TJ. J Physiol 1997; 505: 503-511. 2. Wiseman OJ, Fowler CJ, Landon DN. BJU International 2003; 91: 89-93. 3. Sui GP et al. BJU International 2002, 90, 118-129. 8 Satoshi S1, Sasaki K 2, Igawa Y 1, Nishizawa O1, Chancellor M 3, de Groat W 4, Yoshimura N3 1. Dept. of Urology, Shinshu Univ, School of Medicine, 2. Dept. of Urology, Okayama Univ, School of Medicine, 3. Dept of Urology, Univ of Pittsburgh, 4. Dept of Pharmacology, Univ of Pittsburgh DETRUSOR OVERACTIVITY INDUCED BY INCREASED LEVELS OF NERVE GROWTH FACTOR IN BLADDER AFFERENT PATHWAYS IN RATS Aims of Study It is well known that neurotrophic factors such as nerve growth factor (NGF) is required for the differentiation and maturation of cells in the central and peripheral nervous system and that it can also affect the functional and morphological properties of peripheral sensory neurons. Previous study has demonstrated that NGF levels increased in the spinal cord and hypertrophied bladders in rats with spinal cord injury. In addition recent studies revealed that intrathecal administration of NGF-antibody can neutralize NGF in the spinal cord and reduce NGF levels in bladder afferent pathways, resulting in suppression of detrusor overactivity after spinal cord injury 1). Overall, these data suggest that NGF may be involved in inducing hyperexcitability of bladder afferent pathways that underlies the emergence of detrusor overactivity after spinal cord injury. Thus, to reinforce this hypothesis, we investigated the effects of chronic intrathecal application of NGF on micturition reflex in normal spinal intact rats.

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Methods Adult female Sprague-Dawley rats (204-256 g) were used. An intrathecal catheter was implanted at the level of the L6-S1 spinal cord following a laminectomy at the Th11 vertebra under halothane anesthesia. Three to four days after intrathecal catheter implantation, the intrathecal catheter was connected to an osmotic mini pump for continuous delivery of either vehicle (artificial cerebrospinal fluid, n=7) for 2 weeks or NGF (200 µl of 1.0 mg/ml) for either one (n=5) or two (n=7) weeks. Seven and fourteen days after intrathecal injection of either vehicle or NGF, awake continuous cystometry (CMG) was performed. During CMG, voided volume (VV), intercontraction interval (ICI), maximal voiding pressure (MVP), pressure threshold for voiding (PT) and baseline intravesical pressure (BP) were measured. After CMG, the L5-6 and S1 dorsal root ganglia (DRG) were removed under anesthesia from vehicle- or NGF-treated rats. DRG tissues were also obtained from untreated spinal intact rats (n=3). In L5, L6 and S1 DRG, ELISA measurements were performed in each animal to determine tissue NGF levels. Total protein concentration for the same samples was also determined. All tissue NGF values were standardized by tissue protein levels and expressed as pg/mg of total protein. Results Fig. 1 - In CMG, ICI and VV were significantly decreased in NGF treated rats in a time dependent manner compared with vehicle-treated rats. * P < 0.05, ** P < 0.01

Table 1 – During CMG, MVP, BP and PT were not significantly changed by NGF treatment. In ELISA measurement, NGF levels in L6 and S1 DRG significantly increased in NGF treated rats compared with untreated and vehicle-treated rats. However, no significant difference was found in NGF levels between the groups treated with NGF for 1 and 2 weeks. NGF levels in L5 DRG were not significantly different in untreated, vehicle- and NGF treated rat. * P< 0.05 compared with vehicle treated rats. Untreated n Vehicle n NGF 1W n NGF 2W n MVP (cmH2O) 38.0 ± 2.8 7 38.0 ± 3.0 5 37.6 ± 3.1 7 PT (cmH2O) 9.6 ± 0.58 7 11 ± 1.3 5 9.7 ± 0.68 7 BP (cmH2O) 5.9 ± 0.6 7 7.2 ± 2.2 5 6.6 ± 0.4 7 NFG L6 (pg/µg) 27.8 ± 2.6 3 30.8 ± 2.6 6 44.0 ± 4.1* 6 49.4 ± 5.2* 7 NGF S1 (pg/µg) 31.4 ± 7.1 3 35.2 ± 2.2 6 42.0 ± 2.3* 6 45.2 ± 2.9* 7 NGF L5 (pg/µg) 29.1 ± 7.8 3 34.3 ± 3.2 6 32.0 ± 3.1 5 37.1 ± 3.9 7 Conclusions Intrathecal application of NGF at the lumbosacral spinal cord increased NGF levels in L6 and S1 DRG, which contain bladder afferent neurons, and induced detrusor overactivity. Thus it is concluded that increased NGF levels in bladder afferent pathways are at least in part responsible for emergence of detrusor overactivity, which is often seen after spinal cord injury, and that detrusor overactivity become more severe with the longer duration of exposure of afferent neurons to NGF. Therefore it is likely that rats treated with exogenous NGF could be a good animal model for the study of neurogenic detrusor overactivity

sham NGF 1W NGF 2W0

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and that targeting NGF levels in bladder afferent pathways could be effective for the treatment of detrusor overactivity. Reference 1. J Urol 2002 Nov;168(5):2269-2274 9 Allard J1, Francomme C1, Bernabé J1, Denys P2, Chartier-Kastler E3, Giuliano F4 1. Pelvipharm, 2. CHU Raymond Poincaré, 3. CHU Pitié-Salpétrière, 4. CHU Kremlin-Bicêtre ELECTRICAL STIMULATION OF THE L6 AND S1 SPINAL NERVES REDUCES THE BLADDER OVERACTIVITY INDUCED BY CYCLOPHOSPHAMIDE IN ANESTHETIZED RATS Aims of Study It has been hypothesized that the positive effects of sacral nerves neuromodulation on bladder overactivity was due to an inhibition of the activity of afferent C-fibers. To ascertain this hypothesis, we investigated to which extent electrical stimulation of either A-δ fibers alone or A-δ+C-fibers present in the L6 and S1 spinal nerves (corresponding to the sacral nerves in humans) could alleviate bladder overactivity induced by cyclophosphamide injection. Methods All experiments were carried in isoflurane-anesthetized Wistar rats. Chemical irritation of the bladder responsible for overactivity was induced by intraperitoneal delivery of cyclophosphamide (CYP) delivery (150 mg/kg, 48h before the experiment) and saline injection (VEH) was used as control. To determine threshold intensities for A-δ fibers or A-δ+C-fibers, neurograms were performed by placing a recording electrode on the pelvic nerve and a stimulating electrode on either the L6 or S1 ipsilateral spinal nerve in both CYP and VEH treated rats (4 groups of 3 rats). ES consisted of square wave pulses of 0.2 ms duration. Intensity tested ranged from 25 µA to 4 mA. The impact of continuous ES of both the left L6 and right S1 spinal nerves at intensities specifically recruiting either A-δ fibers or A-δ+C-fibers on transvesical cystometry was assessed in 4 other groups of 6 rats treated with CYP or VEH (named VEHA-δ, VEHA-δ+C, CYPA-δ and CYPA-δ+C). Transvesical cystometry was performed with a perfusion rate of 50 µl/min warm saline through the bladder dome, and bladder pressure was continuously monitored through the same catheter. Cystometry was performed and recorded for 30 min (control recording) before the beginning of the L6/S1 spinal nerves electrical stimulation (ES). Results There was no noticeable difference in the neurograms generated from the S1 and L6 spinal nerves, and between CYP and VEH treated rats. According to the neurograms, intensities of 200 µA and 2 mA were chosen to recruit the maximal amount of A-δ fibers without recruiting any C-fibers, and to recruit both A-δ and C-fibers respectively. Pooled results from the control recording (VEHA-δ+VEHA-δ+C and CYPA-δ+CYPA-

δ+C) showed that CYP treatment resulted in a significant increase in the frequency of voiding contractions (5.3±0.6 to 8.6±1.4 h-1, p=0.04) and non-voiding contractions (1.0±0.4 to 3.9±1.1 h-1, p=0.02). Two way ANOVA with repeated measures showed that continuous ES of the L6/S1 spinal nerves at 200 µA, 20 Hz, marginally reduced the frequency of voiding contractions in control rats (VEHA-δ, 4.0±0.8 h-1 during the ES versus 6.3±0.8 h-1 before the ES of the L6/S1 spinal nerves, p=0.23) whereas it significantly reduced the frequency of voiding contractions in CYP treated rats (CYPA-δ, 6.2±1.1 h-1 during the ES versus 10.9±2.2 h-1

before the ES of the L6/S1 spinal nerves, p=0.03). As a matter of consequence, whereas frequency of voiding contractions was significantly greater in the CYP treated group than in the VEH group before the ES of the L6/S1 spinal nerves at 200 µA (p=0.03), there was no significant difference in the frequency of voiding contractions after ES of the L6/S1 spinal nerves between these 2 groups (p=0.3). The frequency of non-voiding contractions in the VEH group, which was consistently low, was not affected by ES of the L6/S1 spinal nerves at 200 µA (0.5±0.3 h-1 after the ES versus 0.6±0.4 h-1 before the ES of the L6/S1 spinal nerves, p=0.9). In contrast, the frequency of non-voiding contractions was high in the CYP group, and significantly decreased by ES of the L6/S1 spinal nerves at 200 µA (0.2±0.2 h-1 after the ES versus 4.2±1.9 h-1 before the ES of the L6/S1 spinal nerves, p=0.009). Although there was a drastic difference in the basal

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frequency of non-voiding contractions in the CYP group (0.6 h-1 in the VEH group versus 4.2 h-1 in the CYP group), two-way ANOVA with repeated measures could not find a significant effect of the treatment. ES of the L6/S1 spinal nerves at 200 µA also favorably changed other parameters of cystometry in the CYP group (i.e. it increased pressure threshold for initiation of contraction, decreased basal pressure after micturition and maximal pressure during micturition). Those changes were however marginal. ES of the L6/S1 spinal nerves at higher intensities (2 mA) resulted in the quasi suppression of the voiding contractions, and was accompanied by continuous leakage of urine at the urethral meatus. Conclusions ES of the L6 and S1 spinal nerves at an intensity allowing recruitment of A-δ fibers, but not C fibers, lowered the number of voiding contractions in CYP treated rats to a level non significantly different from the value observed in control rats. These results support the ability of ES of the L6 and S1 spinal nerves to reduce bladder overactivity in a pathophysiological model of chemical irritation of the bladder mimicking interstitial cystitis.

10 Yoshiyama M1, de Groat W1 1. Department of Pharmacology, University of Pittsburgh School of Medicine SUPRASPINAL AMPA AND NMDA GLUTAMATERGIC TRANSMISSION IN THE MICTURITION REFLEX IN THE RAT Aims of Study Previous studies revealed that glutamatergic transmission mediated by AMPA and NMDA receptors in the lumbosacral spinal cord plays an essential role in the micturition reflex pathway. The present study was conducted to determine if glutamatergic mechanisms in the brain as well as the spinal cord are important for the control of micturition, by evaluating the effect of intracerebroventricular (i.c.v.) as well as intrathecal (i.t.) administration of an AMPA receptor antagonist and an NMDA receptor antagonist on the micturition reflex in the urethane-anesthetized rat. Methods Female Sprague-Dawley rats (240-300 g) were anaesthetized with urethane (1.2 g/kg s.c.). The trachea was cannulated with a polyethylene tube (PE-240) to facilitate respiration. To administer drugs by the i.c.v. route, the rat was placed in a stereotaxic apparatus and a small craniotomy was performed in order to insert a 30-gauge needle into the right lateral ventricle. The needle connected with PE-10 polyethylene tube for i.c.v. injection was introduced stereotaxically: the tip of the needle located in the right lateral ventricle was at 0.8 mm posterior to bregma, 1.4 mm lateral to midline, and 3.8 mm below the surface of the skull. For i.t. catheterization, the occipital crest of the skull was exposed and the atlanto-occipital membrane was incised on its midline. A catheter (PE-10) was inserted through the slit and passed caudally to the L6-level of the spinal cord. A transurethral bladder catheter (PE-50) connected to a pressure transducer was used to record the bladder pressure during cystometrograms when the bladder was filled with a constant infusion (0.04 ml/min) of physiological saline and allowed to empty around the catheter. Drugs used were LY215490, a competitive AMPA receptor antagonist and MK-801, a non-competitive NMDA receptor antagonist. All values are expressed as mean ± S.E.M. Repeated measures analysis of variance (ANOVA) and Dunnett multiple comparisons test were used when appropriate for statistical data analysis. For all statistical tests, P<0.05 was considered significant. Parameters measured included: bladder contraction amplitude (BCA), pressure threshold for inducing micturition (PT), volume threshold for inducing micturition (VT), residual volume (RV) and voiding efficiency (VE).

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Results Table 1: Effects of LY215490 on the voiding parameters in the urethane-anesthetized rats i.c.v. (µg) (n=6) BCA (cm H2O) PT (cm H2O) VT (ml) RV (ml) VE (%) 0 37 +/- 3 2.6 +/- 0.4 0.67 +/- 0.17 0.39 +/- 0.13 40 +/- 9 0.01 33 +/- 5 6.5 +/- 1.8 1.06 +/- 0.31 0.99 +/- 0.31* 14 +/- 5** 0.1 8 +/- 5** 22.5 +/- 3.5** 1.84 +/- 0.15** 1.82 +/- 0.15** 1 +/- 1** 1 4 +/- 4** 22.9 +/- 3.5** 1.93 +/- 0.15** 1.92 +/- 0.15** 1 +/- 1** i.t. (µg) (n=5) 0 29 +/- 3 2.4 +/- 0.4 1.11 +/- 0.17 0.74 +/- 0.21 38 +/- 9 0.01 28 +/- 3 2.3 +/- 0.4 1.10 +/- 0.14 0.76 +/- 0.24 38 +/- 15 0.1 12 +/- 5** 7.5 +/- 2.8 1.77 +/- 0.20* 1.65 +/- 0.22* 8 +/- 4* 1 8 +/- 5** 9.3 +/- 2.4* 1.93 +/- 0.25** 1.87 +/- 0.27** 5 +/- 3* Table 2: Effects of MK-801 on the voiding parameters in the urethane-anesthetized rats i.c.v. (µg) (n=5) BCA (cm H2O) PT (cm H2O) VT (ml) RV (ml) VE (%) 0 32 +/- 2 4.1 +/- 0.7 0.83 +/- 0.18 0.54 +/- 0.17 39 +/- 9 0.6 31 +/- 2 6.4 +/- 2.1 0.99 +/- 0.15 0.83 +/- 0.15 17 +/- 7 6 6 +/- 3** 25.4 +/- 5.4** 1.56 +/- 0.11** 1.55 +/- 0.12** 0.8 +/- 0.5** 60 4 +/- 2** 21.6 +/- 5.4** 1.66 +/- 0.16** 1.66 +/- 0.17** 0.4 +/- 0.4** i.t. (µg) (n=6) 0 26 +/- 1 4.2 +/- 0.5 1.08 +/- 0.17 0.41 +/- 0.14 61 +/- 11 0.6 27 +/- 2 3.4 +/- 0.3 1.04 +/- 0.16 0.42 +/- 0.14 57 +/- 12 6 26 +/- 2 6.4 +/- 1.6 1.26 +/- 0.23 0.72 +/- 0.22 42 +/- 15 60 12 +/- 4** 13.1 +/- 5.5 1.44 +/-0.24* 1.31 +/- 0.30* 14 +/- 11* Conclusions I.c.v. as well as i.t. administration of AMPA or NMDA glutamatergic receptor antagonists suppressed BCA, increased PT, RV and VT, and decreased VE, in the urethane-anesthetized rat. These data indicate that AMPA and NMDA glutamatergic mechanisms in the brain as well as the spinal cord are essential for controlling micturition. 11 Blyweert W1, Van der Aa F 1, De Ridder D 1 1. Department of Urology, UZ Gasthuisberg, Catholic University of Leuven CANNABINOID THERAPY IN DETRUSOR OVERACTIVITY: LOCAL VERSUS SYSTEMIC EFFECT IN A SPINALISED RAT MODEL Aims of Study Systemic administration of cannabinoids has got a beneficial effect in detrusor overactivity, both in human clinical trials and in animal models. Cannabinoids exert their function through the cannabinoid receptors CB1 and CB2. CB1 receptors are distributed widely throughout the central nervous system including the peri aqueductal grey and the spinal cord. CB1 immunoreactivity has also been demonstrated in human and rodent bladders. There is immunohistochemical evidence for an upregulation of CB1 receptors in neurogenic bladders and in inflammatory disease. CB2 receptors are mainly located on immunological cells. To our knowledge, the peripheral contribution of cannabinoid therapy never has been studied in detail. We investigated the role of the cannabinoid receptors located on the spinal level and in the bladder in the beneficial effect of cannabinoid administration in detrusor overactivity.

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Therefore we compared the urodynamical effect of intraperitoneal vs. intravesical administration of a cannabinoid agonist and antagonist in a spinal cord injured rat model. Methods On day 0 we surgically injured the spinal cord of 24 female Whistar rats at level T2-T3 under fluothane anaesthesia. Antibiotics (Ampicilline 0.15 mg/kg) were administered every 2 days and a Crédé manoeuvre was performed twice daily. Rats subsequently developed detrusor overactivity. A polyethylene PE50 catheter was implanted on day 14 in the bladder fundus. On day 21 rats were divided in 2 groups, one for intravesical, the other for intraperitoneal drug administration. We performed urodynamics before and after administration of vehicle (10% ethanol in saline), WIN-55,212-2 (1µM in 10ml vehicle) or SR 141716A (1µM in 10ml vehicle). We compared urodynamic parameters (voiding volume, voiding pressure and detrusor pressure) in these 6 groups after drug administration. All parameters were compared using a Kruskall-Wallis Anova, followed by Mann-Whitney U test when significant. Results All rats were paraplegic at day 21 and showed signs of detrusor overactivity when urodynamics were performed with saline (NaCl 0.9%). In the intravesical group, no significant change in urodynamic parameters was observed. In the intraperitoneal group, a significant change in detrusor pressure was found between all groups (p <0.05 according to Kruskall-Wallis). After intraperitoneal vehicle administration, mean detrusor pressure was 28.92 mmH2O. After intraperitoneal WIN-55,212-2 administration, mean detrusor pressure was 19.04 mmH2O. After intraperitoneal SR141716A administration, mean detrusor pressure was 39.41mmH2O. Mann-Whitney U test for the intraperitoneal group showed p=0.02 when comparing vehicle vs. Win-55,212-2; p=0.02 when comparing vehicle vs. SR141716A and p=0.004 when comparing Win-55,212-2 vs. SR141716A. Conclusions Since the spino-bulbo-spinal pathway was interrupted in the spinal cord injured rat model, these observations demonstrate that cannabinoids act not only through central regulatory pathways, but that spinal and bladder CB1 receptors are involved. Intravesical administration seems ineffective, perhaps due to inefficient tissue penetration of the different drugs. Systemic administration of cannabinoid agonists significantly decreases detrusor pressure; systemic application of cannabinoid antagonists significantly increases detrusor pressure. These data demonstrate that the beneficial effect of cannabinoid agonists in detrusor overactivity is not mainly due to cannabinoid action in the brain but also due to a peripheral contribution. Whether this effect is attributed to an activation of cannabinoid receptors on the spinal level, of those located in the bladder or of both is not known. The effect of the cannabinoid antagonists increasing detrusor pressure suggests a working mechanism opposite to a tonically active endocannabinoid system. 12 Palea S1, Lluel P 1, Barras M1, Duquenne C1, Galzin A1, Arbilla S1 1. Sanofi-Synthelabo Recherche ACTIVATION OF 5-HT7 RECEPTORS IS LIKELY TO BE RESPONSIBLE FOR 5-HT EFFECTS IN THE RAT URINARY BLADDER Aims of Study It is known that 5-HT produces potentiation of the neurogenic response of the rat isolated detrusor muscle and bladder contraction in the anesthetized rat (1, 2). We thus decided to characterize pharmacologically the 5-HT receptors involved. Methods Female Wistar rats (250-350g) were used. In vitro: detrusor muscle strips were mounted between two platinum electrodes in 5 ml organ bath filled with a modified Krebs solution (1 µM propranolol, 37°C, 95%

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O2 / 5% CO2). Tissues responses were measured using isometric strain gauges connected to a data acquisition system. After 1 hour of equilibration and a contraction to 80 mM KCl, strips were submitted to electrical field stimulation (EFS, 5 Hz, 50 V, 0.3ms pulse duration, trains of 10 s every min). After stabilization of the EFS-induced contractions, tissues were incubated for 30 min with antagonist or vehicle, then a cumulative 5-HT concentration-effect curve (CRC) was obtained. CRC obtained following antagonist incubation was compared with CRC obtained in vehicle-treated strips from the same animal. 5-HT effects were expressed as percentage of the contractile response to 80 mM KCl. In vivo: Rats were anesthetized with pentobarbital (30 mg/kg ip). The ureters and urethra were ligated, the bladder catheterized through the dome and infused with saline to obtain an intra-vesical pressure (IVP) between 10-20 cmH2O. In preliminary experiments we found that 5-HT at 3, 10, 30 and 100 µg/kg i.v. dose-dependently increased IVP. 5-HT 30 µg/Kg i.v. was administered every 10 min three times (control value), then one dose of antagonist was perfused during 5 min and, after further 5 min, 30 µg/kg iv 5-HT was tested again. This cycle was repeated 4 times using increasing doses of the same antagonist. Results are expressed as % inhibition of IVP in comparison to control values (means of three consecutive responses to 30 µg/kg i.v. of 5-HT). Results In vitro: In basal conditions, 5-HT (0.01-30µM) did not induce any contractile effect. EFS produced contractile responses totally abolished by 1µM TTX. 5-HT (0.01-100 µM) induced a concentration-dependent enhancement of this neurogenic response. The effect of selective antagonists for several 5-HT receptor subtypes on the 5-HT-induced potentiating effect is illustrated in the annexed Table. In vivo: In the presence of the antagonist vehicle, the increases in IVP induced by repeated doses of 30 µg/kg 5-HT were reproducible. R(+) Lisuride (LISU) tested in the range 3-100 µg/kg iv, dose-dependently inhibited 5-HT induced increase of IVP. At the maximal dose tested, LISU (n=5) almost totally inhibited the 5-HT effect (-95±2.4%); the calculated antagonist dose needed to inhibit 50% of the response to 30 µg/Kg 5-HT was 9.2±2.1 µg/kg i.v. Conclusions These results suggest the involvement of 5-HT7 receptors in stimulated rat isolated detrusor muscle and in the bladder of anesthetized rats for the following reasons: a) The selective 5-HT7 receptor antagonist SB 258741 blocks the 5-HT potentiating effect with the expected potency (3); b) pA2 values obtained for LISU and mesulergine correlate with their potencies on 5-HT7 receptors (4,5) but not with the potencies on 5-HT2a /5-HT2c receptors (6); c) in vivo results show that LISU inhibits 5-HT effect on IVP at doses known to abolish vasodilatation mediated by 5-HT7 receptors in anesthetized Wistar rats (7). In conclusion, we have found that 5-HT7 receptor antagonists are active against increased bladder contractility in in vitro and in vivo models, and thus could be useful in the treatment of detrusor overactivity. Table: pD2 values of 5-HT in electrically-stimulated rat detrusor muscle strips and effects of several selective 5-HT receptor antagonists pD2 5-HT Emax

(%80mM KCl)

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pA2 value

6.38±0.08 (n=3)

30.7± 3.6 1-[4-(1-Adamantane carboxamido)butyl]-4-(2-methoxyphenyl)piperazine

5-HT1A 0.1 No effect

6.09 ± 0.06 (n=4)

45.2± 3.6 Mesulergine 5-HT2 / 5-HT7 0.3 7.27±0.12 (n=4)

6.05 ± 0.27 (n=4)

36.7± 13 Ondansetron 5-HT3 0.1 No effect

6.23 ± 0.13 (n=5)

27.1± 5.0 SB204070 5-HT4 0.03 No effect

5.93 ± 0.11 (n=4)

37.4± 2.1 R(+) Lisuride 5-HT7 0.3 7.73± 0.45 (n=4)

6.27 ± 0.12 (n=8)

36.1± 4.4 SB258741 5-HT7 0.3 7.32± 0.22 (n=8)

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References 1. Neurourol. Urodyn. 17: 337-39, 1998. 2. Neurourol. Urodyn. 9: 350-51, 1990. 3. CNS Drug Rev. 8: 90-100, 2002. 4. Proc. Natl. Acad. Sci. U.S.A. 90: 8547-51, 1993. 5. J. Pharmacol. Exp. Ther. 297: 395-402, 2001. 6. Pharmacol. Rev. 46: 157-203, 1994. 7. N. S. Arch. Pharmacol. 359: 331-38, 1999. 13 Salcedo C1, Balsa D1, Enrich A 1, Davalillo S 1, Pellicer T1, Lagunas C 1, Catena J1, Fernández-Serrat A1, Farrerons C 1, Fernández A G1 1. Laboratorios SALVAT SVT-40776, A NEW SELECTIVE M3 MUSCARINIC ANTAGONIST: HUMAN RECEPTOR BINDING PROFILE AND BLADDER EFFECTS IN THE GUINEA PIG Aims of Study Detrusor overactivity incontinence (OAB) is a highly prevalent condition characterised by an increased urinary frequency, urgency and urge incontinence. Muscarinic receptor antagonists are the most widely used therapeutic agents for OAB, but cardiovascular effects related with M2 blocking can limit their clinical use. The aims of the study was to determine the effect of SVT-40776, a novel substituted quinuclidine derivative with high M3 receptor affinity, on the different human muscarinic receptors through radioligand binding assays and to evaluate its activity on the intravesical and arterial pressure in anaesthetised animals. Methods Binding Study: Membranes containing human muscarinic receptors (M1-M5) were obtained from Receptor Biology Inc. Competition studies: [3H]-NMS binding to the membranes was carried out in 96-well filter plates, containing glass fiber type B at room temperature for 1 h. Radioligand binding to muscarinic receptors was determined in the absence and presence of increasing concentrations of antagonists. Non-specific binding was determined in the presence of 10 µM of atropine. At the end of the incubation time, the binding reaction was terminated by vacuum filtration using the Millipore vacuum manifold; filters were washed three times and dried. Scintillation liquid was added to the filters, and the retained radioactivity was quantitated in a scintillation counter (Microbeta, Wallac). The data points derived from the specific binding of [3H]-NMS were analysed using a non-linear curve-fitting programme (GraphPad Prism , GraphPad Software Inc.). Binding parameters were obtained as the best-fit values for the data using the least-squares method. Reagents: SVT-40776, oxybutynin, darifenacin, solifenacin and tolterodine were dissolved in DMSO to prepare a concentrated stock solution of 10 mM. In vivo Study: Animals were anaesthetised by urethane 1.5 g/kg i.p.. A polyethylene catheter (PE-50) was implanted in the bladder via urethra and the bladder empted of urine. Carotid artery and jugular vein were cannulated to register arterial pressure (AP) and as administration route respectively. Bladder and carotid catheters were connected to pressure transducers (Transpac IV) and analysed using PowerLab® Software (ADI System). Through carotid, a baseline AP of 59.8 ± 1.7 mmHg was registered. Bladder was filled with 2.8 ml of saline to obtain a mean pressure of 58.5 (± 2.8) mmHg, which induced regular spontaneous contractions. After obtaining a stable response, the compound was administered by intravenous bolus followed by a cumulative consecutive dose-response protocol (15 min between doses or when stable contractions were obtained). AP was measured on the first 5 min post-dose periods. Amplitude from all bladder contractions (intravesical pressure) was measured during the 15 min period between doses and an amplitude mean calculated for baseline and for each dose. Percentage of variation was calculated vs. baseline effect. Reagents: Concentrated stock solutions of 10 mM were prepared for all the agents. SVT-40776 and solifenacin were diluted in saline. Oxybutynin and tolterodine were diluted in distilled water. Darifenacin was diluted in 10% DMSO in distilled water. Successive dissolutions were prepared with saline.

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Results Binding Study: Table 1. Binding results at M1-M5 recombinat human muscarinic receptors

Affinity (Ki, nM) Ratio Compound

hM3 M1/M3 M2/M3 M4/M3 M5/M3

Oxybutynin 1.6 ± 0.3 2.4 5.7 1.2 3.3 Tolterodine 4.13 ± 1.7 0.6 0.5 0.4 0.6 Darifenacin 3.05 ± 0.2 16.6 29.1 6.9 2.4 Solifenacin 7.3 ± 1.4 0.3 5.9 0.3 0.7 SVT-40776 0.18 ± 0.09 2.0 213.7 1.5 2.1 In vivo Study: Graph 1: Representative trace of dose-response inhibition of spontaneous bladder contractions by SVT-40776

1479

Blad

der 2

(mm

Hg)

70

80

90

100

50.00 58.20 1.06.40 1.15.00 1.23.20 1.31.40 1.40.00 1.48.20 1.56.40 2.05.0034 5 6 7 8 9 10

22/1/03 11.30.27,093

Graph events: 4 = 1 nmols/kg; 5 = 3 nmols/kg; 6 = 10 nmols/kg; 7 = 30 nmols/kg; 8 = 100 nmols/kg; 9 = 300 nmols/kg. Table 2. Comparative results in the guinea pig anaesthetised model.

Compound Intravesical Pressure Inhibition ED25 (nmol/kg i.v.)

Arterial Pressure Increase ED25 (nmol/kg i.v.)

Oxybutynin 181.1 >3000 Tolterodine 299.2 820.4 Darifenacin 53.2 >1000 Solifenacin 200.9 >3000 SVT-40776 17.1 >3000 Conclusions SVT-40776 exhibits high affinity, in the sub-nanomolar range, for the human M3 muscarinic receptor, being, indeed, the most potent ligand among all the reference compounds assayed.

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SVT-40776 shows the highest selectivity of human M3 versus the M2 subtype, among all the reference antagonists tested. All these agents are able to inhibit spontaneous bladder contractions. SVT-40766 is the most potent compound inhibiting these contractions, at the very low doses of 17.1 nmols/kg i.v.. All this agents, apart of tolterodine, do not affect arterial pressure in this model even at the very high dose of 1000-3000 nmols/kg i.v.. 14 Igawa Y1, Zhang X1, Umeda M2, Iwata A2, Nishizawa O1, Taketo M3, Manabe T4, Matsui M4, Andersson K5 1. Shinshu University School of Medicine, 2. Research Center Kyoto, Bayer Yakuin, Ltd, 3. Kyoto University, 4. University of Tokyo, 5. Lund University Hospital IN VIVO AND IN VITRO FUNCTIONAL CHANGES OF THE URINARY BLADDER IN MICE LACKING MUSCARINIC M2 OR M3 RECEPTORS Aims of Study Detrusor muscle function has been studied previously in vitro in both M3 and M2 muscarinic receptor knockout mice, and important gender differences have been suggested [1,2]. However, the urodynamic consequences of lack of M3 or M2 receptors have not been investigated. Studies in mice lacking muscarinic receptor subtypes may offer a possibility to obtain information on which muscarinic receptor subtype is the most important for bladder emptying in vivo, and to what extent non-muscarinic mechanisms can compensate for lack of muscarinic receptor functions. In the present study, bladder function was studied by cystometry and detrusor smooth muscle responses to stimulation of muscarinic and purinergic receptors and to electrical field stimulation (EFS) were investigated in mutant mice lacking M2 or M3 receptors. Methods Male and female mice lacking M3 (M3 KO) or M2 (M2 KO) receptors and matching wild type controls (WT), 18-23 weeks of age, were used. For cystometric studies, a polyethylene catheter (PE-50) was implanted into the bladder, and a separate polyethylene catheter was implanted in the subcutaneous layer of the back for drug administration. Cystometric investigations were performed without any anesthesia 3 days after the operation. Room-temperature saline was instilled into the bladder at a rate of 2.5 ml.h-1. Intravesical pressure and micturition volumes were recorded continuously before and after subcutaneous administration of atropine sulphate (1mg.kg-1). In vitro responses of isolated detrusor muscle strips with intact urothelium to carbachol, ��-methylene ATP (��-Me-ATP) and EFS were also investigated, and are shown as percentages of the maximal contractile response to 118 mM KCl. A Student’s paired two-tailed t-test was used for comparisons between before and after drug administration. Student’s unpaired two-tailed t-test and one-way factorial ANOVA followed by Scheffe’s F-test were used for comparisons between groups. A probability level of <5% was accepted as significant. Results In vivo studies. In males, there was no significant difference in any of the cystometric parameters between WT and M2 KO mice, but M3 KO mice had significantly longer voiding intervals and larger micturition volumes and bladder capacity than WT and M2 KO mice. In females, both M3 KO mice and M2 KO mice had significantly longer voiding intervals and larger micturition volumes than WT mice. There was no difference in post-void residual volumes among these 3 groups. In the WT and M2 KO mice of both genders, atropine significantly decreased threshold and micturition pressures, voiding intervals and micturition volumes, and significantly increased residual volumes and bladder capacity. On the other hand, in the M3 KO mice of both genders, atropine had no effect on any of the parameters. In vitro studies. Carbachol concentration-dependently contracted the bladder strips of WT and M2 KO mice of both genders: the maximal contractions, obtained at 10 �M, were 127±4% and 114±4% in male and female WT mice bladders and 109±4% and 106±5% in male and female M2 KO mice bladders, respectively. In contrast, those values of male and female M3 KO mice bladders were only 8.9±2.2% and 3.9±0.3%, respectively, which were significantly lower than those obtained from WT and M2 KO mice. ��-Me-ATP (0.1– 100 �M) elicited concentration-dependent contractions of the bladder strips from all types of mice. In preparations from male, but not female, M3 KO mice, the ��Me-ATP-induced bladder contractions were

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more pronounced than those from WT and M2 KO mice. EFS produced frequency-dependent contractile responses in all the three groups. The maximal contractile responses to EFS in male and female WT mice bladders were 131±11% and 125±8%, respectively, which were significantly higher than those (68±8%; p<0.01, males; 75±5%; p < 0.01, females) for M3 KO mice bladders. The corresponding values for male and female M2 KO mice bladders were 101±15% and 101±8%, respectively, which were not significantly different from those of WT mice bladders. After 1 �M atropine treatment, the EFS-induced contractions were inhibited by 50% and 33% in male and female WT mice bladders, and by 47% and 30% in male and female M2 KO mice bladders, respectively, but were not affected in M3 KO mice bladders. ��-Me-ATP (30 �M) markedly diminished the atropine-resistant component, and eventually the remaining component in the presence of both atropine (1 �M) and ��-Me-ATP (30 �M) was not further suppressed by addition of TTX (1 �M) in all groups. Conclusions The present results confirm that M3 receptors are the main muscarinic receptor subtype responsible for bladder contraction during voiding, and that the role of M2 receptors is minor. They also show that muscarinic receptors, at least in mice, are not necessary for bladder emptying, suggesting that the non-cholinergic part of bladder contraction can compensate for a defect in the muscarinic mechanisms. References 1. Proc. Natl. Acad. Sci. USA, 2000, 97, 9579-9584. 2. J Neurosci 2002, 22:10627-10632. 15 Yoshida M1, Miyamae K1, Otani M1, Iwashita H1, Masunaga K1, Inadome A1, Ueda S1 1. Dep. of Urology, Kumamoto University School of Medicine COMPARISON OF EFFECTS OF VARIOUS ANTIMUSCARINIC DRUGS ON NORADRENALINE RELEASE FROM HUMAN ISOLATED URETHRA Aims of Study Several antimuscarinic drugs are clinically used, and clinical trials of newly synthesized antimuscarinic drugs for the treatment of overactive bladder are now going. Pharmacological studies have demonstrated the affinity and selectivity for muscarinic receptor subtype, and selectivity for the bladder over other organs. It is well known that muscarinic receptors exist on bladder smooth muscles, and prejunctional site of cholinergic nerve endings in bladder. Muscarinic receptors on cholinergic nerve endings regulate the acetylcholine release from the nerve (1). In addition, several reports (2) have suggested that there are muscarinic receptors on prejunctional site of adrenergic nerve ending, which may regulate noradrenaline releases from the nerves, and have the effects on urethral tones. Therefore, the present study was designed to compare the effects of various antimuscarinic drugs (atropine, pirenzepine, methoctoramine, 4-DAMP, oxybutynin, propiverine and tolterodine) on noradrenaline release in human isolated proximal urethral smooth muscles, using microdialysis method (3). Methods Human urethras (20 male and 2 female: mean age 68.4 years) were obtained from patients undergoing radical cysto-urethrectomy due to bladder carcinoma. Smooth muscle strips were dissected from the proximal urethra of each patient. Microdialysis probe was inserted into each strip, and Ringer solution was perfused into the probe. Each strip with microdialysis probe, which was suspended in an organ bath filled with oxygenated Krebs-Henseleit solution, was connected to an isometric force displacement transducer, and an isometric tension development was recorded. The effects of pretreatment with various antimuscarinic drugs on the contractile responses induced by electrical field stimulation (EFS: supramaximum voltage, 0.5 msec duration, 2-60 Hz and 3 sec train) were evaluated. Furthermore, in noradrenaline release experiments, the dialysate during EFS (supramaximum voltage, 0.5 msec duration, 40 Hz and 3 sec train at 1 min interval for 10 min) was collected, and the amount of noradrenaline released in the dialysate was measured by HPLC with ECD.

385

Results Carbachol (0.01 µM – 1.0 mM) did not cause significant contractile responses, but EFS caused frequency-dependent contractile responses in human isolated proximal urethral smooth muscles. Pretreatment with pirenzepine (M1 selective drug) at 1.0 µM significantly decreased the EFS-induced contractile response and noradrenaline release (p<0.01), although the compound at 0.01 and 0.1 µM had no effects on both contractile response and noradrenaline release. In contrast, methoctoramine (M2 selective drug) (0.01 - 1.0 µM) showed significant and concentration-depended increases in EFS-induced contractile response and noradrenaline release (p<0.01). Pretreatment with 4-DUMP (M3 selective drug), propiverine, oxybutynin and atropine at the concentration up to 1.0 µM had no significant effect on the EFS-induced contractile responses and noradrenaline releases. However, pretreatment with tolterodine (0.01 - 1.0 µM) caused concentration-dependent increases in EFS-induced contractile response and noradrenaline release in human urethral smooth muscles. Conclusions The present data demonstrate that excitatory M1 receptor and inhibitory M2 receptor subtypes exist on prejunctional site of adrenergic nerve endings in human proximal urethral smooth muscles, and that pharmacological effects of various antimuscarinic drugs on human urethral smooth muscles are different. Some drugs may have prejunctional inhibiting or excitatory action of noradrenaline releases from adrenergic nerve endings, which may have effect on the human proximal urethral tone. Table - Effects of various antimuscarinic drugs (1.0 µM) on EFS-induced contractile responses and noradrenaline releases in human proximal urethral smooth muscles

Antimuscarinic drug Contractile response, % Noradrenaline release %

Atropine (n=8) Pirenzepine (n=8) Methoctoramine (n=8) 4-DAMP (n=8) Oxybutynin (n=10) Propiverine (n=10) Tolterodine (n=10)

102.0±3.8 86.6±3.5* 129.6±3.6* 105.2±2.8 100.3±4.4 108.2±4.0 126.5±3.7*

103.5±2.4 87.6±3.1* 132.5±3.5* 103.9±2.2 105.1±3.3 111.6±3.6 128.6±4.0*

Value is represented as % of control value in each parameter. Control values are EFS-induced contractile responses and noradrenaline releases without drug treatment. EFS conditions are supramaximum voltage, 0.5 msec duration, 40 Hz and 3 sec train at 1 min interval for 10 min. * P < 0.05; significantly different from control values

References 1. Urologia Internationalis 61: 135-141, 1998 2. Annals of Clinical Research 20: 356-366, 1988. 3. European Journal of Pharmacology 357: 213-219, 1998 16 Cialdai C1, Lecci A1, Lazzeri M2, Giuliani S1, Maggi C A1, Turini D2 1. Menarini Ricerche, 2. Ferrara University EFFECT OF PROTAMINE PRETREATMENT ON DETRUSOR HYPERACTIVITY INDUCED BY INTRAVESICAL CAPSAICIN IN ANAESTHETIZED GUINEA-PIGS. Aims of Study Protamine complexes glycosamminoglycan mucosal layer and can destroy bladder urothelium facilitating the penetration of bacteria and irritants within the bladder wall (1, 2). However, it has been recently shown that, beyond the above-mentioned barrier function, the urothelium could have a role in the modulation of both afferent and efferent neurotransmission (3, 4). Functional TRPV-1 (capsaicin) receptors are

386

expressed on urothelial cells and their stimulation induce the release of nitric oxide and ATP from these cells (3, 4). In turn, both nitric oxide and ATP could exert a variety of effects on smooth muscle cells, efferent and sensory nerve terminals. In this study we investigated the effect of protamine pretreatment on capsaicin-induced bladder hyperactivity in anaesthetized guinea-pigs. Methods Male Dunkin-Hartley guinea-pigs (400-500 g) were anaesthetized with urethane (1.6 g/kg, sc). A double-lumen polyethylene catheter was inserted into the bladder dome for intravesical administrations, liquid infusion, and pressure recordings. Following a baseline cystometry performed with saline (100 µl/min for 90 min, Period 1), protamine sulphate (15 mg in 1.5 ml) (Group 2), or saline (Group 1) were instilled intravesically and kept for 30 min. Urethral leakage of solutions was avoided by clamping the preputium during the treatment. Afterwards, the clamp was removed and the cystometry was repeated by infusing saline (100 µl/min for 90 min, Period 2); the solution for intravesical infusion was then changed, and capsaicin (10 µM) was infused for 90 min (Period 3). The following urodynamic parameters were evaluated in each period (mean±s.e.m. of n experiments): bladder capacity (BC, µl), mean amplitude of micturition contractions (MAC, mmHg), pressure threshold for micturition reflex (PT, mmHg), and duration of micturition (MD, s). Results were analyzed through Student’s t test for unpaired or paired data, when applicable. Results Basal urodynamic parameters were similar in both groups. Protamine treatment did not change urodynamic parameters as compared to saline. In controls (Group 1), the PT for the activation of micturition reflex decreased during the 2nd Period as compared to baseline. Capsaicin infusion induced bladder hyperactivity in both protamine- and saline-pretreated animals; although this hyperactivity was more prominent in saline-pretreated guinea-pigs, the difference was not significant. The MD increased in both groups although not significantly, wheras other urodynamic parameters did not change following capsaicin, as compared to baseline values. Table Period 1 Period 2 Period 3 Group Parameter Baseline (n) Saline (n) Capsaicin (n) 1 BC (µl) 1802±167 (11) 2047±233 (12) 883±105** (12) 2 BC (µl) 1620±252 (12) 1357±193 (10) 845±73* (9) 1 MAC (mmHg) 24±4 (11) 24±5 (12) 26±6 (12) 2 MAC (mmHg) 22±4 (12) 29±6 (10) 24±4 (9) 1 PT (mmHg) 9.3±1.6 (11) 5.7±1.2** (12) 5.2±1.3 (12) 2 PT (mmHg) 7.8±1.8 (12) 7.8±1.9 (10) 6.2±1.6 (9) 1 MD (s) 58±20 (11) 33±4 (12) 57±12 (12) 2 MD (s) 36±4 (12) 35±5 (10) 46±6 (9) *P<0.05 and **P<0.01 vs previous period. Conclusions Intravesical capsaicin elicits bladder hyperactivity in guinea-pigs, as previously assessed in both rats and hamsters (5). In a previous study in guinea-pigs, intravesical capsaicin induced an inhibition of the micturition reflex, however cystometries were carried out at high flow rates, where excitatory effects could not be highlighted (6). The urodynamic changes accompanying capsaicin-induced hyperactivity vary in different species, possibly reflecting both the nature and the amount of neurotransmitters contained in TRPV-1-expressing neurons and the differential expression of receptor types at the post-junctional level. In the guinea-pig bladder TRPV-1-expressing neurons contain significant amounts of both tachykinins and CGRP, and both excitatory tachykinin NK1 and NK2, and inhibitory CGRP receptors are expressed on detrusor muscle and postganglionic fibers (5, 7). Because of this arrangement, it is likely that a compensation between excitatory and inhibitory signals occurs, and capsaicin does not change the MAC. In rats, where both detrusor muscle and postganglionic fibers express tachykinin but not CGRP receptors, capsaicin increases the MAC, whereas in hamsters the same stimulus decreases the MAC, possibly because of the paucity of tachykinins in this species (5). Protamine neither changed the urodynamic parameters during cystometries, nor significantly altered capsaicin-induced bladder hyperactivity, suggesting that transmitters released by the urothelium do not affect neurotransmission in this paradigm. Despite this, a decrease in the PT during the 2nd period was observed in controls but not in protamine-

387

treated animals. This decrease in the PT could be interpreted as the animal correlate of the sensitization that occurs in humans following repeated bladder distensions (8), therefore mediators released by the urothelium (prostanoids?) might be involved in this effect. References (1) J Urol (1996) 160, 206. (2) Am J Physiol Renal Physiol (2002) 283, F242. (3) PNAS (2001) 98: 13396-13401. (4) Nature Neuroscience (2002) 5: 856. (5) Auton Neurosci (2001) 91: 37. (6) J Urol (1999) 161, 998. (7) Regulatory Peptides (2001) 101, 1. (8) Pain (1998) 76: 61. 17 Lu S1, Sacks M1, Qu-Petersen Z1, Peng H1, Pruchnic R1, Somogyi G1, Cannon T1, Huard J1, de Groat W1, Chancellor M1 1. University of Pittsburgh School of Medicine NICOTINIC RECEPTORS MODULATED CONTRACTILE ACTIVITY AND COMPLIANCE OF MUSCLE-DERIVED STEM CELLS INCORPORATED INTO ACELLULAR SCAFFOLDS FOR URETHRAL AND BLADDER RECONSTITUTION Aims of Study To explore the contractile activity and biomechanical properties of muscle-derived stem cells (MDSC) incorporating into small intestinal submucosa (SIS) scaffolds for bladder and urethral reconstitution. Methods After harvesting hindleg muscle from mice, MDSC were isolated using the pre-plate technique. The late plate cell population were transduced with retrovirus-LacZ gene and then suspended in Hank’s balanced salt solution for use. MDSC were placed into single layer SIS cell culture inserts. Twenty-five different preparations of MDSC and/or SIS were then incubated at 37 �, for either 10 or 20 days. LacZ staining and Masson-Trichrome staining were performed to reveal MDSC and SIS. Immunohistochemical staining for the muscle type acetylcholine receptor (AChR), Hoechst staining for nuclei and Desmin staining for myoblasts/myotubes were also performed. The histochemical properties of MDSC were examined after different times in culture. Using the biaxial testing method, the tissue deformations were measured continuously using real-time video marker tracking. Areal strain was calculated to quantify the compliance of the specimens. Then, the data obtained were compared between different groups. Fifty additional preparations of SIS and MDSC were incubated at 370C, for 1, 4 and 8 weeks, respectively. MDSC/SIS were examined histologically and also mounted in a bath and the property of the isometric contractions was measured. Electrical field stimuli, succinylcholine, carbachol, KCl, Ca++- free Krebs solution with EGTA and distilled water were applied into the bath sequentially. Results Histologically, LacZ, and Masson-Trichrome staining revealed MDSC could migrate and distribute throughout the SIS and form myotubes. The mean (± S.E.) areal strain in the control group (n=4) of the non-incubated SIS was 0.182 ± 0.027 (n=5). After 10 days incubation, the mean (± S.E.) areal strain in MDSC/SIS (0.247 ± 0.014, n=5) was not significantly different (P = 0.142) from that of incubated SIS alone (0.200 ± 0.024, n=6). After 20 days incubation, the mean (± S.E.) areal strain of MDSC/SIS (0.255 ± 0.019, n=5) was significant higher (P = 0.027) than that of incubated SIS alone (0.170 ± 0.025, n=5). The biaxial testing results exhibited the classic biological non-linear stress-strain response. The specimens were in a state of nearly pure biaxial strain with negligible shear. Multiple staining for AChR, Hoechst and Desmin demonstrated AChR expression in MDSC/SIS preparations after 4- and 8-week incubations but not after 1-week incubations. In MDSC/SIS, spontaneous contractile activity (SCA) was noted in 4 -week (5/6 specimens) and 8-week cultures (8/8 specimens) but

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not in 1-week cultures (N=11). All SIS control groups after 1 (N=11), 4 (N=6) and 8-week (N=8) incubation did not show any activity. In 4-week MDSC/SIS, the frequency and amplitude of SCA were decreased in 2/5 specimens by succinylcholine 10 uM and 5/5 specimens by succinylcholine 20uM. In 8-week MDSC/SIS, the frequency and amplitude of SCA were decreased in 8/8 specimens by succinylcholine 10 uM and 20 uM. Electrical field stimulation, carbachol and KCl did not alter the frequency, amplitude and pattern of the SCA in MDSC/SIS. SCA was blocked by Ca++-free Krebs solution with EGTA 200 µM or distilled water. Conclusions MDSC can be incorporated into SIS forming myotubes capable of contracting. MDSC/SIS exhibited better compliance than incubated SIS alone in 20 days preparations. The histochemical demonstration of AChR expression in MDSC/SIS preparations supports the view that AChRs are responsible for contractile activity in MDSC/SIS. The contractile activity of this 3-dimensional construct is Ca++ dependent and modulated by nicotinic receptors. MDSC seeding of acellular matrix may become a functional sling to reengineer the deficient sphincter or as contractile bladder augmentation. 18 Chermansky C1, Tarin T1, Kwon D1, Cannon T1, de Groat W1, Huard J1, Chancellor M1 1. University of Pittsburgh INTRAURETHRAL MUSCLE DERIVED CELL INJECTIONS INCREASE LEAK POINT PRESSURE IN A RAT MODEL OF INTRINSIC SPHINCTERIC DEFICIENCY Aims of Study Intrinsic sphincteric deficiency (ISD) denotes a malfunction of the striated urethral sphincter. One approach to treating ISD has been the use of injectable, intraurethral, bulking agents. The goal of these injectables is to restore mucosal coaptation and its “seal effect” contribution to the continence mechanism (1). Despite the short-term success achieved with injection therapy, the technique is hindered by reabsorption, the need for multiple injections, allergic reactions, and migration. Also, these bulking agents work to produce a functional obstruction. As such, they compensate for rather than correct the underlying pathophysiology of ISD. Research into newer ISD treatments has focused on striated sphincter reconstruction. One such approach under investigation involves using skeletal muscle derived cells (MDC) to regenerate damaged urethra. The preplate technique is used to isolate cells that, through six serial passes, adhere last onto collagen-coated flasks. Some of these cells have stem cell like properties and are termed MDC. Our objective was to determine if allogenic MDC could restore sphincteric function in rats with ISD. Methods Under halothane anesthesia (2%), 25 adult female Sprague-Dawley rats underwent cauterization of tissues lateral to the mid-urethra to produce ISD. One week after cauterization, 1.5x106 MDC, transfected with Lac Z, were injected into the mid-urethra of 16 rats. These rats were divided into 3 groups, which were evaluated 2-weeks (n=8), 4-weeks (n=5), or 6-weeks (n=3) after MDC injection. In another group, 9 rats were injected with Hanks’ Balanced Salt Solution (HBSS) after cauterization. These rats, divided into 3 groups of 3 rats each, were evaluated 2, 4, or 6 weeks after injection of HBSS. A 3/10 cc insulin syringe was used to inject either 10 µl of MDC suspended in HBSS (approximately 750,000 cells) or HBSS only into each lateral wall of the mid-urethra. A total of 20 µl (1.5x106 cells) of MDC were injected into the urethra of each MDC rat. As a control, 9 normal rats, divided into 3 groups of 3 rats each, underwent a sham operation during which the urethra was exposed but not cauterized. Subsequent evaluation was performed in these rats at 2, 4, or 6 weeks. Under urethane anesthesia, all rats underwent cystometry and leak point pressure (LPP) testing to evaluate bladder and sphincteric function, respectively. LPP testing was performed with the use of the vertical tilt table/intravesical pressure clamp technique. The location of the MDC was assessed using Lac Z staining. Differences in striated muscle layer and innervation between the 3 groups were noted with fast myosin heavy chain and anti-protein gene product (PGP) 9.5 staining, respectively.

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Results The injection of MDC into the mid-urethra increased LPP without affecting bladder function. The mean LPPs of control rats 2,4,and 6 weeks after a sham operation were 49.8±1.3 cm H2O, 51.2±1.5 cm H2O, and 51.6±2.0 cm H2O, respectively. The mean LPPs of the rats 2, 4, 6-weeks after cauterization and HBSS injection were 17.2±1.4 cm H2O, 26.9±1.9 cm H20, and 25.5±1.3 cm H20, respectively. The mean LPPs of the rats 2, 4, and 6 weeks after cauterization and MDC injection were 38.2±2.2 cm H2O, 43.1±2.6 cm H2O, and 51.5±0.9 cm H2O, respectively. When compared to cauterized rats injected with HBSS and matched respective to time, the increased LPPs in each MDC injected group were significantly higher (p<0.001). Histological analysis showed that the MDC contributed to striated muscle regeneration. Also, the MDC injected urethra had an intact striated muscle layer and more nerves in comparison to the HBSS injected and control urethras, which had disrupted muscle and few nerves. Figure: The effect of MDC injection on LPP. When compared to cauterized rats injected with HBSS and matched respective to time, the increased LPPs seen in each MDC injected group were significantly higher (∗ denotes p<0.001 for each of the 3 pairs of groups). C denotes control, H denotes HBSS injected, and M denotes MDC injected.

C H M C H M C H M0

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Conclusions The injection of intraurethral MDC improved sphincteric function in rats with ISD. There was no alteration in bladder function with either cauterization or MDC injection. Allogenic MDC persisted and achieved functional improvement for 6 weeks without significant inflammatory response. Histology showed that the MDC had integrated well within the striated muscle layer of the cauterized mid-urethra. In addition, the striated muscle layer of the MDC injected urethra was intact and had more nerves than the cauterized urethra injected with only HBSS. The periurethral injection of MDC may provide an attractive alternative to current therapies for ISD. Reference

1. Appell R: Injection Therapy for Urinary Incontinence. In: Campbell’s Urology, 8th ed. Edited by PC Walsh, AB Retik, ED Vaughn Jr., and AJ Wein. Philadelphia: WB Saunders Co., vol. 2, part V, 1172-1186, 2002.

* * *

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19 Haltbakk J1, Hanestad B R1, Hunskaar S1 1. Dep. of Publ. Health & Prim. Health Care, University of Bergen MEASURING QUALITY OF LIFE (QOL) IN MEN WITH URINARY SYMPTOMS: USING THE WORLD HEALTH ORGANISATION’S INSTRUMENT WHOQOL-BREF Aims of Study It has been suggested that reported international differences in the prevalence and severity of LUTS might reflect cultural differences in the perception and willingness to report symptoms. This suggestion has called for a broader focus of LUTS and the men’s perception of their living conditions and QOL has been considerably debated. The generic QOL instruments reported on in urologic research are developed in North America and the UK. Therefore, their relevance may be questioned when applied to other cultural settings. Another critic of such instruments is that their contents are restricted to functional status, perceived health or impact of disease, which is not QOL per se. World Health Organisation has developed a QOL instrument (WHOQOL) with the attempt to face these critics. WHOQOL is developed within fifteen international field centres simultaneously to ensure cross-cultural applicability. In addition, the WHOQOL reflects a broad view of QOL embedded in a cultural, social and environmental context. The drawback by broad generic instruments is their lack of sensitivity and discriminatory properties, and despite their excellent content validity they might have restricted utility. The aim of this study was to establish whether the short version (WHOQOL-bref) differentiates between severity groups in men with tentative diagnosis of LUTS awaiting urologic evaluation. Methods The sample consisted of men waiting for urologic evaluation. Based on the general practitioners’ information in the referral letter to an urologist in secondary health care, the tentative diagnoses of BPH and LUTS were set for 612 patients who entered a waiting list for urologic evaluation. After being informed by letter about their attendance to the list, 480 patients gave their consent to participate and filled in a questionnaire containing I-PSS and WHOQOL-bref. Results from I-PSS (range 0-35) originated the severity groups: Mild (0 –7), moderate (8 – 19) and severe (20 – 35). The WHOQOL-bref results in a profile of 4 domains (range 4 – 20), each of which relates to a particular dimension of QOL: Physical health, psychological, social relations and environmental domain. Two single items (range 0 – 4) which measures overall QOL, and overall health perception. Results In the table below, scores for each of the dimensions of the WHOQOL-bref are shown. Overall, men with moderate and severe symptoms have lowered levels of QOL compared to the men with mild symptoms. Differences between the three groups are most apparent in overall QOL and in the physical health dimension, while no differences are found for the psychological and social relations’ domains. Table: Mean of the various WHOQOL domains in each I-PSS severity group. Domain

I-PSS severity group (no.)

N

Mean

± SD

95% Confidence interval

Severity groups (no.)-(no.) with significant diff. *

Mild

(1)

58

4.03

0.70

3.85-4.22

Moderate (2) 226 3.66 0.84 3.55-3.77

Overall QOL

Severe (3) 128 3.55 0.97 3.38-3.72

(1)-(2) (1)-(3)

Mild

(1)

59

3.58

0.91

3.34-3.81

Moderate (2) 228 3.36 0.95 3.24-3.49

Overall health perception Severe (3) 129 3.22 0.97 3.05-3.39

(1)-(3)

Mild

(1)

60

15.92

2.46

15.28-16.55

Moderate (2) 223 14.67 2.79 14.30-15.04

Physical health

Severe (3) 126 13.74 3.09 13.20-14.29

(1)-(2) (1)-(3) (2)-(3)

391

Mild

(1)

59

15.75

1.95

15.23-16.26

Moderate (2) 223 14.94 2.39 14.63-15.26

Psychological

Severe (3) 127 15.16 2.32 14.75-15.57

Mild

(1)

60

14.50

2.25

13.92-15.08

Moderate (2) 221 14.39 2.57 14.05-14.73

Social relations

Severe (3) 127 14.37 2.71 13.90-14.85

Mild

(1)

61

15.95

2.07

15.41-16.47

Moderate (2) 223 15.31 2.17 15.02-15.60

Environment

Severe (3) 126 14.99 2.25 14.60-15.39

(1)-(3)

* ANOVA Bonferroni with significant difference at 0.05 level. Conclusions The WHOQOL is thus able to differentiate between men in particular severity groups with tentative diagnosis of LUTS and the instrument apparently discriminates at best in the physical domain. In various samples of chronic conditions in general, physical measures of QOL have a broader range of mean than psychosocial measures (1), which might indicate that physical aspects of QOL is more affected by chronical conditions than the psychosocial aspects. As particular domains of QOL are deteriorating across severity groups, the WHOQOL-bref has a potential to detect improvement in these factors following treatment. As WHOQOL is constructed for international purposes, a potential use of the instrument is to internationally investigate how its domains are associated to the detected international differences in prevalence and severity of LUTS. Reference 1. Sprangers MAG, Regt de EB, Andries F, Agt van HME, Bijl RV, Boer de JB, et al. Which Chronic Conditions Are Associated with Better or Poorer Quality of Life? J Clin Epidemiol 2000;53:895-907. 20 Sereika S1, Engberg S1, Engberg R1 1. University of Pittsburgh PREDICTORS OF GENERAL HEALTH-RELATED QUALITY OF LIFE IN OLDER ADULTS WITH URINARY INCONTINENCE Aims of Study Urinary incontinence (UI) is a prevalent chronic condition that impacts community-dwellling, older adults. Research studies have shown the UI can have a negative impact on quality of life (QOL). However, it is not clear what factors may impact QOL in persons with UI. The purpose of this secondary analysis was to describe general health-related QOL and to identify predictors (demographic, incontinence characteristics, functional status, and comorbidity) of general health-related QOL in older adults with UI. Methods A secondary data analysis was performed using baseline data from a larger, ongoing, randomized controlled trial investigating the effectiveness of a relapse prevention intervention based on self-efficacy theory and Marlatt’s relapse prevention model to sustain continence levels following six weeks of individualized behavioral therapy (biofeedback-assisted pelvic floor muscle training and strategies to prevent urinary loss). The sample for this secondary study consisted of 237 adults with mixed urge and stress incontinence (57.8%, n=137) of 7.6 years duration (SD=10.1, Range=0.3-64.0), reporting a mean number of 2.73 urinary accidents (SD=2.77, Range=0.15-19.43) and 9.62 voids (SD=4.37, Range=2.00-41.57) per day. Subjects were predominantly white (96.2%, n=228), female (83.1%, n=197), cognitively intact (MMSE > 24) older adults, aged 60.0 to 94.7 years (Mean=77.0, SD=8.3). Most had completed at least a high school education (86.9%, n=206; Mean=13.1 years, SD=3.0, Range=5-23), were retired

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(90.3%, n=214), widowed (47.4%, n=113), living alone (51.5%, n=122), and had neither a paid nor informal (friend or family member) caregiver (64.1%, n=152). Subjects reported on average 4.8 co-existing conditions (SD=2.6, Range=0-13) and were prescribed a mean 4.5 medications (SD=3.2, Range=0-18). General health-related QOL was assessed using the MOS SF-36, yielding indices measuring health status on global physical and emotion domains as well as over eight individual areas. The Continence Program Assessment Form II was used to acquire information on continence history (year of UI onset) and medical history (number of prescribed medications. A one-week bladder diary provided a self-reported record of urinary voiding and accidents. Functional status was assessed across several domains: activities of daily living (ADLs), cognitive function, mobility, and affective function. Performance of ADLs was assessed using the OARS Physical and Instrumental Activities of Daily Living scales. Folstein’s Mini Mental State Examination (MMSE) and the Clock Drawing Test (CDT) were used to measure cognitive function. Mobility was evaluated using a Performance Based Toileting Assessment, which considers the need for assistance during ambulation and the time to walk or propel a wheelchair 15 feet and prepare to toilet. The Geriatric Depression Scale (GDS) was used to characterize the subject’s affective function. Comorbidity was assessed as the self-reported number of co-existing medical conditions from a modified version of the Charlson Comorbidity Index. Subject sociodemographic and socioeconomic characteristics were collected using a research center-developed sociodemographic profile. Data were collected as part of a comprehensive baseline assessment conducted over two visits to the subject’s home by a project nurse and nurse practitioner. Subjects kept one-week bladder diaries between baseline assessment visits. Appropriate descriptive statistics were calculated to characterize the sample and general health-related QOL. General health-related QOL means from this sample were compared with published normative data for general health-related QOL using one-sample t-tests. Stepwise linear regression analyses were used to identify predictor variables using p-values for entry and removal of .05 and .10, respectively when determining the final set of predictor variables. Results Compared to normative data on the MOS SF-36, subjects with UI reported significantly lower scores on the physical component scale (p<.001) and significantly higher scores on the mental component scale (p<.001). Examination of the eight individual areas showed scores significantly lower for UI subjects compared to published norms on physical functioning (PF), bodily pain (BP), and vitality (VT), while scores for UI patients were significantly higher than norms on social functioning (SF), role-emotional (RE), and mental health (MH). No significant differences were found for role-physical (RP) and general health (GH). (See Figure 1.) Stepwise regression analyses identified poorer performance of instrumental ADLs, higher number of comorbid conditions, more depressive symptomatology, having a paid or informal caregiver, living alone, using assistive devices, and having a higher voiding frequency as negatively impacting physical health-related QOL (R-squared=.44, p<.001). For mental heath-related QOL, less depressive symptomatology, lower accident frequency, using assistive devices, having a caregiver, and considering religion or spirituality as important were identified as significant predictors of higher levels of mental health-related QOL (R-squared=.37, p<.001).

Figure 1: MOS SF-36 Health Status Profile

0

20

40

60

80

100

PF RP BP GH VT SF RE MH PCS MCS

UINormative

393

Conclusions This study illustrates the negative impact that lower urinary tract symptoms may have on the general health-related QOL. Patients with UI tended to have lower levels of QOL associated with physical health compared to age-matched normative data, specifically in the areas of physical functioning, bodily pain, and vitality. UI and urinary frequency, potentially modifiable health problems, were identified as predictors of poorer mental health and physical health QOL. 21 Coyne K1, Zhou Z2, Versi E2 1. MEDTAP International, Bethesda, MD, 2. Pharmacia Corporation, Peapack, NJ, USA NOCTURIA HAS A SIGNIFICANT IMPACT ON HEALTH-RELATED QUALITY OF LIFE Aims of Study Nocturia is defined as waking at night one or more times to void [1]. The condition, associated with overactive bladder and other non-lower urinary tract causes, is a very bothersome urinary symptom. However, clinical data on nocturia is limited. The objective of this study was to assess the impact of nocturia, and the number of nightly nocturia episodes, on HRQL and sleep. Methods A national survey was performed in the US to measure the prevalence of overactive bladder (OAB) and nocturia. The survey used a clinically validated, computer assisted telephone interview. The survey included questions regarding nocturia and other urinary variables. Respondents were categorized into control and OAB groups. A nested case-control study was performed among respondents with OAB and age- and gender-matched controls. Subjects completed a series of questionnaires including an OAB-specific HRQL and symptom questionnaire, the OAB-q, the Medical Outcomes Study (MOS) Short-Form 36, and the MOS-Sleep Scale. Descriptive analyses, t-tests, and analysis of variance with post hoc comparisons were used to analyze the data. Results A total of 5204 participated in the NOBLE program. Of the 1769 questionnaires sent to telephone respondents, 919 (52%) respondents were included in a nested case-control study. The study group consisted of 60% females with a mean age of 54.2 years. 79% of respondents reported at least 1 episode of nocturia in the previous 4 weeks; of these 41% reported >1 episode of nocturia/night and 30% reported ≥2 episodes/night. The age of participants reporting nocturia ≥2 episodes/night was significantly greater (60.8 years) than that of participants not reporting nocturia (52 years; p<0.0001). When examining the HRQL impact of nocturia categorically and incrementally, similar findings were noted. Compared with subjects with no nocturia, Table 1 shows those reporting nocturia (≥2 episodes/night) had significantly (p<0.02) reduced HRQL in all OAB-q subscales. Table 1. OAB-q subscale scores in subjects with nocturia vs no nocturia controlling for age, gender, and clinical conditions

OAB-q subscales1

[Mean (SE)]

No nocturia (0 to <1) N=505

Nocturia (≥1<2) N=178

Nocturia (≥2) N=216

P value

Symptom bother 15.1 (0.9) 23.1 (1.5) 32.5 (1.4) <0.001 Coping 92.3 (0.9) 87.0 (1.4) 82.2 (1.3) <0.02 Concern 92.3 (0.9) 87.7 (1.4) 81.2 (1.3) <0.001 Sleep 89.0 (1.0) 79.1 (1.6) 67.9 (1.5) 0.0001 Social 97.3 (0.5) 94.7 (0.9) 93.0 (0.8) ≥2 vs 0, p<0.02 HRQL total 92.7 (0.7) 87.1 (1.2) 81.3 (1.1) <0.001 1 Higher scores indicate better HRQL; higher symptom bother scores indicate greater symptom bother

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In all OAB-q subscales, increasing episodes of nocturia were associated with reductions in HRQL with significant differences (p <0.05) observed for all comparisons with the group of respondents with <1 episode/night (Figure 1). The greatest differences were noted in the sleep subscale with significant (p<0.0001) decreases with each additional nocturia episode. On the MOS-Sleep scale, the number of hours of sleep per night was significantly lower for participants with ≥ 2 nocturia episodes/night (6.7 hours) versus those with no nocturia (7.0 hours; p<0.02). Participants with ≥2 nocturia episodes/night also reported significantly poorer scores on the somnolence subscale and significantly (p<0.05) greater impairment on the Sleep Index I subscale than those with <2 nocturia episodes/night. Interestingly, the sleep subscale of the OAB-q was more sensitive than the MOS sleep index scale for determining the impact of nocturia.

Conclusions Nocturia causes significant distress and, even one episode per night, has a significant impact on both sleep and HRQL. Indeed, each additional episode of nocturia is associated with an incremental reduction in HRQL. References 1. Van Kerrebroeck P, Abrams P, Chaikin D, et al. The standardisation of terminology in nocturia: report from the Standardisation Sub-committee of the International Continence Society. Neurourol Urodyn 2002; 21:179-83.

Symptom Sleep Coping Concern Social0

25

50

75

1000-<1 (n=505)1-<2 (n=178)2-<3 (n=133)3-<4 (n=48)

≥4 (n=35)

Nocturia episodes

Bother Interaction

a

a

b

b

b

c

c

c c

ns

nsb

nsd

dns

ns

1 Higher score indicates better HRQL; higher symptom bother scoreindicative of greater symtpom bother

a p<0.0001 for all groups comparison;b p<0.001 for all group comparison except where noted;c p<0.01 for all group comparisons;d p<0.05 for all group comparisons

c

OA

B-q

sub

scal

e sc

ore

1

Figure 1. OAB-q subscale scores by number of nocturia episodes controllingfor age, gender, and clinical comorbidities

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22 Pleil A M1, Kelleher C J2, Allen L E1, Ray Reese P3 1. Pharmacia Limited, High Wycombe, UK, 2. Guy's & St. Thomas' Hospital Trust, London, UK, 3. Consultant, North Carolina, USA THE HEALTH-RELATED QUALITY OF LIFE (HRQOL) IMPACT OF THE SYMPTOMS OF NOCTURIA IN PATIENTS WITH OVERACTIVE BLADDER Aims of Study Prior to the ICS standardisation paper(1) there was no firm consensus regarding a definition for nocturia. Nocturia is rarely considered as a stand-alone symptom but nocturia symptoms deemed problematic were consistently reported by subjects with overactive bladder (OAB) participating in a large multinational clinical trial. The objectives of this study are to:

1. Describe the relationship between the symptoms of nocturia and various physical and psychological domains of health related quality of life (HRQoL). 2. Evaluate how a change in patients’ perception of nocturia as a problem impacts upon HRQoL. Methods Subjects enrolled in a 12-week double-blind safety and efficacy trial and a 12-month open-label extension provided data for these analyses. Efficacy endpoints and HRQoL were assessed at baseline, 12 weeks and then at 3 and 12 months after rollover.

HRQoL was measured using the King’s Health Questionnaire (KHQ), a multidimensional disease-specific measure for patients with OAB(2). The KHQ is scored on a 0(best) to 100(worst) scale. The impact of urinary symptoms including nocturia (“getting up at night to pass urine”) was based on the self-reported symptom severity checklist of the KHQ. Patients rated the degree of effect on their life of certain bladder symptoms (“a little”, “moderately” or “a lot”). The absence of a rating was interpreted as “no problem”. Nocturia improvement was defined as a positive change from baseline at 12 months post-rollover or a change from a response category to a “no problem” status. No improvement in nocturia symptoms was defined as no change in response, or moves from less to more problematic ratings. The patient population used for these analyses was the intent to treat (ITT) open-label population for whom a translated KHQ was available and who reported nocturia as a symptom at baseline (n = 838). Multiple regression was used to assess the impact of symptoms on KHQ domains. Differences in mean KHQ change scores (split plot repeated measures ANCOVA with visit and improvement in bladder condition as factors, with age, gender and country as covariates) were tested. Significance levels were adjusted for multiple comparisons by the Hochberg method. Results In the regression analysis, nocturia was a significant predictor of sleep/energy domain scores. Frequency and bladder pain were also significant, albeit with smaller beta coefficients. Table 1 shows sleep/energy score improvement from baseline was better (negative numbers reflect improvement in domain score) in improvers than non-improvers at each time period. Patients reporting improvement in nocturia symptoms at 12 months also had significantly more improvement in physical (Table 2) and psychological domain scores (Table 3) at 12 weeks with the exception of personal relationships and general health domains. Table 1 -Change Scores: KHQ Sleep/Energy Scores for Nocturia Patients With/Without Improvement Timeline No Improvement

Mean (SD) [95% CI] Improvement Mean (SD) [95% CI]

Baseline to 12 weeks -5.7 (1.1) [-7.9, -3.5] -14.7 (1.2) [-17.1, -12.3] Baseline to months -8.3 (1.1) [-10.5, -6.0] -19.9 (1.2) [-22.3, -17.5] Baseline to 12 months -4.6 (1.1) [-6.9, -2.4] -21.4 (1.2) [-23.8, -19.0]

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Table 2 -Change Scores: KHQ “Physical” Domains for Nocturia Patients With/Without Improvement (baseline to 12 weeks) KHQ Domain No Improvement –

Mean (SD) [95% CI] Improvement Mean (SD) [95% CI]

Incontinence Impact -11.1 (1.5) [-13.9, -8.2] -20.5 (1.6) [-35.2, -29.0] Role Limitations -13.0 (1.5) [-15.9, -10.1] -22.7 (1.6)[-25.7, -19.6] Physical Limitations -10.5 (1.5) [-13.3, -7.6] -20.0 (1.6) [-23.0, -16.9] Severity (coping) Measures -8.5 (1.1) [-10.7, -6.3] -14.5 (1.2) [-16.8, -12.2] General Health Perceptions -1.0 (0.9) [-2.7, 0.7] -1.7 (0.9) [-3.5, 0.2] Symptom Severity -6.1 (0.7) [-7.5, -4.7] -13.6 (0.8) [-15.1, -12.1] Table 3 –Change Scores: KHQ “Psychological” Domains for Nocturia Patients With/Without Improvement (baseline to 12 weeks) KHQ Domain No Improvement

Mean (SD) [95% CI] Improvement Mean (SD) [95% CI]

Social Limitations -6.9 (1.1) [-9.1, -4.7] -13.4 (1.2) [-15.7, -11.0] Personal Relationships -4.6 (1.5) [-7.6, -1.6] -8.6 (1.6) [-11.8, -5.4] Emotions -8.0 (1.2) [-10.4, -5.6] -13.7 (1.3) [-16.3, -11.2] Conclusions The degree to which OAB patients experience nocturia symptoms impacts on their self-reported HRQoL. Nocturia symptoms are particularly important in explaining sleep/energy domain scores, although frequency and bladder pain are also associated with sleep/energy domain scores. Changes in perception of the effect of nocturia symptoms are related to changes in HRQoL. Patients reporting an improvement in nocturia also report improvements in a number of domains of HRQoL most notably sleep/energy. The results suggest that nocturia is frequently perceived as a problem by OAB patients and effective treatments that reduce nocturia symptoms will likely improve patient quality of life. References (1) Abrams P, Cardozo L, Fall M, Griffiths D, Rosier P, Ulmsten U, vanKerrebroeck P, Victor A, Wein A, Neurology and Urodynamics, 2002 21:167-178 (2) British J. Obstet. Gynaecol. 1997;104:1374-1379 23 Dallosso H1 1. University of Leicester THE ASSOCIATION OF DIET AND OTHER LIFESTYLE FACTORS WITH OVERACTIVE BLADDER: A LONGITUDINAL STUDY IN WOMEN. Aims of Study Very few longitudinal studies on incontinence have been conducted, and to date none have investigated lifestyle risk factors. The present study investigates the role of dietary and non-dietary lifestyle factors in the incidence of overactive bladder.

Methods A random sample of 20,244 women aged 40 years and over living at home was sent a postal questionnaire on urinary symptoms and lifestyle. Two reminders were sent to non-responders at 4-week intervals (response rate 65%). The questions on urinary symptoms were developed for the study [1] in line with recommended standards [2]. A detailed investigation into non-response at baseline [3] found little evidence of non-response bias in the reporting of urinary symptoms. Responders to the first and second mailings of the baseline questionnaire were asked to complete a 130-item validated food frequency questionnaire [4]

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(response rate 65%). Follow-up data on urinary symptoms were collected in a postal survey one year later (response rate 91.2%). There was no difference in the year one drop out rate between baseline OAB cases and non-cases. Logistic regression was used to investigate the association of diet and other lifestyle factors with the incidence of overactive bladder (OAB). For the purposes of the study OAB was defined as one or both of the symptoms urge leakage (“a strong desire to pass urine that results in leakage of urine before reaching the toilet” at least several times a month), and urgency (“a strength of urgency once you feel the need to pass urine that is typically very strong or overwhelming”). Results Follow-up data on urinary symptoms were collected from 6,424 women. Overall the prevalence of OAB at baseline was 16.3%, and increased with age. At the Year-1 follow-up the incidence rate of OAB was 9.2% (492 new cases). In the multivariate model there were significantly increased risks for onset of overactive bladder with being overweight or obese (p=0.05), smoking (p=0.04) and the consumption of fizzy drinks (p=0.03), while there were reduced risks with high consumptions of vegetables (p=0.02), bread (p=0.001) and chicken (p=0.005) (with additional adjustments made for age, physical functioning and presence of stress incontinence at baseline). Conclusions The present longitudinal study provides evidence that some aspects of diet and lifestyle may be independent risk factors in the aetiology of overactive bladder. The association with fizzy drinks confirms current clinical advice to reduce consumption. Lifestyle interventions such as weight loss, smoking cessation and a change in diet could also be important in the prevention and treatment of the condition. References 1 Authors names removed to protect anonymity. An epidemiological study to establish the prevalence of urinary symptoms and felt need in the community: the Leicestershire MRC Incontinence Study. Journal of Public Health Medicine 2000: 22:427-434. 2 Abrams P, Cardozo L, Fall M, Griffiths D, Rosier P, Ulmsten U et al. The standardisation of terminology of lower urinary tract function: report from the Standardisation Sub-Committee of the International Continence Society. American Journal of Obstetrics and Gynecology 2002: 187:116-126. 3 Authors names removed to protect anonymity. An investigation into non-response bias in a postal survey on urinary symptoms. BJU International 2003, in press. 4 Bingham SA, Welch AA, McTaggart A, Mulligan AA, Runswick SA, Luben R et al. Nutritional methods in the European Prospective Investigation of Cancer in Norfolk. Public Health Nutrition 2001: 4:847-858. 24 Tincello D1, Walker A2 1. University of Leicester, 2. Interstitial Cystitis Support Group SYMPTOMS, TREATMENTS AND QUALITY OF LIFE AMONG MEMBERS OF THE INTERSTITIAL CYSTITIS SUPPORT GROUP IN THE UK Aims of Study Interstitial cystitis is an uncommon and poorly understood inflammatory bladder disease. Prevalence estimates and epidemiological data on the disease and its associations are available from the United States of America, but there are no good quality data from the United Kingdom. The Interstitial Cystitis Support Group (ICSG) is a registered charity for sufferers, and conducted a questionnaire survey of its members in 1999 to investigate duration of symptoms, delay in diagnosis and treatment variations. Methods A postal questionnaire was sent to all members of the ICSG and asked about risk factors, associated diseases, symptoms, exacerbating and relieving factors, coping strategies, medications received and their effectiveness and impact upon lifestyle of the disease. Information was sought on the length of time to diagnosis, and the way in which the diagnosis was reached. Data were entered onto SPSS v 11. Data are

398

described as median (range) or number (%) and comparisons were made using Mann Whitney U test. Odds ratios are presented with 95% Confidence intervals (OR, 95% CI) Results 736 of 1148 (64%) questionnaires were returned. 696 patients (94.6%) were women. Women were slightly younger at the onset of symptoms (45 vs 53 years, p=0.05). The median duration of symptoms was 9 years (1-59) and the median duration of symptoms before diagnosis was 3 (0-60). 37 patients (5%) (36 women) reported an affected family member, of whom 50% were female. 36% patients reported sensitivity or allergy to drugs; and 43% sensitivity to foodstuffs. 61% had symptoms of irritable bowel syndrome; 35% reported arthritis, 55% back pain; 22% sinusitis, 28% candidal infection; 29% bacterial cystitis; 25% migraines, and 31% constipation. Back pain (OR 2.47; 1.24, 4.90); thrush (OR 4.90; 1.49, 16.13); cystitis (OR 5.01; 1.52, 16.46) were more common in women. The following triggers of disease onset were identified: pelvic surgery (18%), bacterial cystitis/thrush (17%), emotional stress (17%). 87% patients described at least daily pain when their symptoms were at their worst, and 37% described daily pain at the time of the survey. Pain occurred in the bladder (56%), urethra (49%), lower abdomen (37%), & suprapubic area (28%). Symptoms included: frequency (92%), urgency (84%), nocturia (87%), pain (63%), dyspareunia (45%), post-coital frequency (41%), bladder spasms (54%), & urethral pain (63%). Median reported frequency was 10 (2-70), nocturia 3 (0-20), at the time of survey and 20 (1-92), 8 (0-48) respectively at the worst time. Patients reported having received the following treatment: antidepressants (47%); antibiotics (66%); cimetidine (36%); antihistamines (5%); NSAIDs (40%); anticholinergics (37%); pentosan polysulphate (12%); DMSO (33%); anticonvulsants (2%); potassium citrate (32%), and sodium bicarbonate (52%). %% patients had undergone diversionary or storage surgery to the bladder. 47% patients admitted to moderate depression or worse. 51% patients considered that IC had “completely taken over” their life. 49% found sexual intercourse a considerable problem (30), or were unable to tolerate it at all (19%). 73% were diagnosed by a urologist, 11% by the patient themselves, and 8% by a (uro)gynaecologist. The diagnostic procedure involved a cystoscopy in 47% of cases and a combination of tests in 31%. The number of cystoscopies per patient was 2 (0-60), and 85% patients had a general anaesthetic for this. 83% patients had been referred to a specialist, of whom 75% were urologists. Conclusions In keeping with data from the USA, IC in the UK is a disease of delayed diagnosis, and chronic progression. Patients experience severe symptoms and disturbance to quality of life. Many patients have received mutiple treatments. It is noteworthy that several treatments of proven efficacy are used infrequently in this cohort of patients. Education of medical staff is still necessary. 25 Rendeli C1, Padua L1, Ausili E1, Girardi E1, Caliandro P1, Salvaggio E1 1. Catholic University- Pol. A. Gemelli HEALTH-RELATED QUALITY OF LIFE IN ADOLESCENTS WITH SPINA BIFIDA: A PROSPECTIVE MULTIDIMENSIONAL STUDY Aim of the study In order to assess the Quality of Life (QoL) in young Spina Bifida (SB) patients and to correlate it with conventional disability measures and clinical picture, we performed a prospective multidimensional study, according to the outcome research methodology, using the most used general health status questionnaire and validated conventional clinical and disability measurements. Methods 30 consecutive young patients with Spina Bifida (mean age 16.4, range 14-18 years) were evaluated with a prospective multidimensional study by means of: 1) clinical assessment: we acquired personal data concerning educational level ,urological aspects etc through a case form and after we performed a detailed clinical examination (neurological and physical rehabilitation); 2) self-administred questionnaire for general health (SF-36 Short-Form Health Survey)(1); 3) standardised disability measurements (FIM:functional independence Measure, BI:Barthel Index,DI: Deambulation Index). Relationships between disability

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measurement, patient-oriented picture and conventional clinical assessment were evaluated. Statistical analysis was performed using the STAT-SOFT (OK, USA) package. Results As expected, the disability was inversely related only (r: 0.50, p=0.006) to the physical aspect of QoL of patients. Similarly, the disability was inversely related ( r:0.35, p=0.005 ) to the emotional aspect of QoL of patient’s parents. Unexpectedly, the mental aspects of QoL of patients were inversely related to disability, in fact severe disability was not associated with higher psychological distress and patients with less disability had difficulty in daily activity due to emotional problems. The findings at clinical examination, especially proximal deficit of inferior limbs (r: 0.75, p<0.04), were usually related to higher disability and lower physical aspects of QoL. Conclusions Spina Bifida (SB) is a congenital malformation of the neural tube, and accounts for as many as 4,7 in 10000 live births (2). SB affects the growth and development of the central nervous system, and the musculoskeletal and genitourinary systems. We performed a study to assess QoL and disability in young patients with SB and to correlate it with the clinical picture. In our SB sample, as expected, disability is strongly associated with clinical impairment of the proximal muscles of the lower limbs. In fact, proximal muscles are mainly involved in walking and generally in the motor functions of the lower limbs. With regard to QoL, the pattern appears more complex. Expectely, higher disability and severe muscle deficit of the lower limbs are associated with a reduction in the physical aspect of QoL. On the contrary, unexpectedly, mental aspects of QoL is inversely related to disability: patients with low disability, for example normal walking ability or total autonomy, presented emotional problems higher than patients with severe disability. When we analysed which emotive aspect is mainly involved, evaluating the subscores, we observed that the patients with low disability have difficulty in daily activity due to emotional problems. Conversely, patients with high disability , referred that the inability to perform daily activity was due to physical problems and they had a good quality of life from an emotional point of view. We observed that greater feelings of global self esteem in physical appearance were associated with greater severity of disability. We hypothesize that the sfincterial problem plays a key role in this QoL pattern, in fact it must be noted that even patients with low disability have severe sfincterial problems. Probably the patients with lower disability have more social activity and spend most of their time among healthy people, but they know their disease and hide their severe urological problems. Conversely, patients with severe disability perceive that the limitations are not due to emotional problems but mainly to physical and they accept their condition emotively. Regarding the emotional picture, we believe that parents may greatly influence this aspect of patient’s QoL. Some studies assess parents’ perception of QoL and perception of youth but the relationship is complex and still matter of debate (3-6). The main lack of this study is the small sample studied. Notwithstanding, the study of this comprehensive and multiperspective assessment of the disease provided several significant results. In conclusion, our results provide data against an easy and linear inverse correlation between disability and QoL in SB adolescent patients. Assessment of QoL, and particularly the emotional results, give us useful information for clinical practice: patients with mild disability concerning inferior limbs (patients who are able to walk, run and have total autonomy) but urological problems need psychological support more than patients with severe whole disability. References

1. Ware JE. SF-36 Physical and Mental Health Summary Scales: A User’s Manual. Boston: New England Medical Centre; 1994.

2. Mc Donnell GV, McCann JP. Issues of medical management in adults with spina bifida. Child’s Nerv Syst 2000;16:222-227

3. Minchom PE, Ellis NC, Appleton PL, Lawson V, Boll V, Jones P, Elliott CE. Impact of functional severity on self concept in young people with spina bifida. Arch Dis Child 1995. 73:48-52

4. Landgraf JM, Abetz L, Ware JE. The CHQ user’s Manual. Second printing Boston, MA: HealthAct, 1999 5. Andresen EM, Meyers AR. Health-Related Quality of Life Outcome measures. Arch Phys Med Reahabil 2000;

81 (Suppl 2): S30-S45. 6. Kirpalani HM, Parkin PC, Willan AR, Fehlings DL, Rosenmbaum PL, King D, Van Nie AJ. Quality of life in

spina bifida: importance of parental hope. Arch Dis Child 2000. 83: 293-7

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26 Jünemann K P1, Halaska M2, Rittstein T 3, Bruenjes R4 1. Dept. Urology, University Hospital Kiel, 2. Dept. Gynecol., University Prague, Czech Republic, 3. Dept. Gynecol., Kladno, Czech Republic, 4. Apogepha Arzneimittel GmbH, Dresden PROPIVERINE VS. TOLTERODINE – EFFICACY AND TOLERABILITY IN PATIENTS WITH DETRUSOR OVERACTIVITY Aims of Study Comparison of the efficacy, tolerability and of the impact on quality of life of propiverine and tolterodine in the treatment of patients with idiopathic detrusor overactivity. Methods In a randomised, double-blind, multicentre clinical trial patients with idiopathic detrusor overactivity were treated with 15 mg propiverine b.i.d. or 2 mg tolterodine b.i.d. for 28 days. The maximum cystometric capacity was determined at baseline and after 4 weeks of therapy. The difference of both values was used as primary endpoint. Secondary endpoints were voided volume per micturition, efficacy evaluation by the investigator, tolerability, post void residual, and quality of life measured by the King´s Health Questionnaire Score. Results The per-protocol population included 155 patients (propiverine: 75, tolterodine: 80; age: 56.3 ± 14.9 years, female: 128 (82.6%)), the intention-to-treat population 201 patients (propiverine: 100, tolterodine: 101; age: 56.3 ± 14.9 years, female: 158 (78.6%)) and the safety population 202 patients. Efficacy: In the per-protocol population the mean maximum cystometric capacity increased significantly (p<0.01) in both groups. For propiverine there was an increase from 209.2 ± 64.5 to 265.1 ± 112.2 ml (+55.8 ± 116.2 ml). For tolterodine there was an increase from 202.6 ± 67.1 to 272.6 ± 116.1 ml (+70.1 ± 101.3 ml). Both groups were comparable (p = 0.42). This was confirmed by the median values (propiverine +44.0 ml; tolterodine +47.5 ml). The voided volume per micturition increased by 31.4 ± 60.8 ml in the propiverine group, and by 27.7 ± 56.3 ml in the tolterodine group. In the final efficacy evaluation the investigators judged propiverine as very good or good in 60 %, moderate in 24 %, and insufficient in 15 % of the cases. Tolterodine was judged as very good or good in 58 %, moderate in 23 %, and insufficient in 19 % of the cases. Tolerability and safety: 42/100 patients in the propiverine group and 43/102 in the tolterodine group experienced adverse events. The most common adverse event, dry mouth, occured in 20 patients in the propiverine group and in 19 patients in the tolterodine group. 16 premature study terminations were documented. In both groups 6 of these terminations were caused by adverse events. No relevant changes in post void residual were observed. The scores for the quality of life improved comparably in both groups (propiverine: from 53.7 to 45.4; tolterodine: from 52.0 to 44.6). Conclusions This study demonstrates for the first time comparable efficacy, tolerability, and improvement in the quality of life of 15 mg propiverine b.i.d. and 2 mg tolterodine b.i.d. in the therapy of the symptoms of detrusor overactivity.

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27 Cappellano F1, Bertapelle P 2, Catanzaro F1, Del Popolo G3, Cervigni M4, Spinelli M5, Curti P6, Minardi D7, Leone G8, Giardiello G9, GINS Group O B10 1. Multimedica S.S. Giovanni, 2. CTO-CRF-MA Torino, 3. Careggi Firenze, 4. IDI Nancy Roma, 5. Osp. Magenta, 6. Policlinico B. Roma, Verona, 7. Policlinico U 1° Ancona, 8. Osp Civitanova M, 9. Medtronic Italia, 10. GINS group Italy EVALUATION OF INCONTINENCE QUALITY OF LIFE (I-QOL) SUBSCALES IN PATIENTS SUFFERING FROM DETRUSOR OVERACTIVITY(DO):IMPACT OF SACRAL NEUROMODULATION Aims of Study Sacral neurmodulation has been used as an effective way to treat LUTS. We know from previous studies how much urinary incontinence (UI) globally affects QoL: patients affected by UI due to DO frequently report a limiting behavior and social embarrassment anecdotally . Aim of this study is to investigate the influence of sacral neuromodulation (SNM) on quality of life (QoL) in general and on avoidance and limiting behavior, psychosocial impacts and social embarrassment in patients who underwent to a permanent implant using a validated domain specific QoL questionnaire. Methods From May 1998 to September 2002 226 pts (76 males, 150 females , mean age 53 years) affected by lower urinary tract symptoms, were enrolled in a National prospective registry after a permanent implant of a sacral nerve neurostimulator. Seventy-one pts affected by urinary urge incontinence (55 idiopathic, 16 neurogenic) were asked to complete a validated self reporting incontinence domain specific questionnaire ( I-QoL) before and after 3 to 24 months post permanent implant. The questionnaire consist of 22 question, for each a ranking 1-5 is assigned, the score is sum and then normalized in a 0-100 scale in which 0 is the lower QoL level. We analyzed into the questionnaire (as previously reported by Patrick and others , Urology 53-1:1999 ) three subscales to verify not only the global improvement of QoL but also formal and quantitative impact of SNM on behavioral and psychosocial field . Results Compared with the baseline the QoL index significantly improved at each follow up visit and strongly correlated with the decrease in number of incontinence episodes and pads use at a mean follow up of months. Analysis of subscales showed also a significant improvement in avoidance and limiting behavior, social embarrassment and psychosocial impacts (Tab. 1 ). Number of daily incontinent episodes decrease from 6.6 at baseline to 0.5 at last follow-up in non neurogenic group and from 5.8 to 2 in neurogenic group.

Tab.1. Total I-QoL and subscales scores in implanted patients at 24 mos follow-up I-QoL Total Avoidance

behavior Psychosocial impact

Social Embarrassment

Non neurogenic BASELINE

33 35 36 25

Non neurogenic 24 mos follow-up

83 84 86 75

Neurogenic BASELINE

38 43 38 28

Neurogenic 24 mos follow-up

50 59 50 38

Conclusions As previously reported SNM is effective therapy for urge incontinence due to DO and has a positive impact on patients’ QoL. From our new insight it has a particular influence on psychosocial impacts and social embarrassment with a good correlation with clinical outcome. Also pts with some incontinence episodes and using 1 pad a day regain self consideration and have a quite normal social life and a psychological well being.

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28 Norton C1, Burch J1, Kamm M A1 1. St Mark's Hospital PATIENTS’ VIEWS OF A COLOSTOMY FOR FAECAL INCONTINENCE Aims of Study Faecal incontinence affects over one percent of community-dwelling adults. Formation of a permanent stoma is often seen as a last resort when all other interventions have failed. However, no previous study has examined patients’ views of a colostomy to manage faecal incontinence. We aimed to examine the outcome of stoma surgery for faecal incontinence from the patient’s perspective. Methods People with previous formation of a colostomy to manage faecal incontinence were recruited either via an advertisement in the magazine of the British Colostomy Association or from those operated at a specialist colorectal hospital. Four questionnaires were sent, asking about current stoma management, operative experience, previous incontinence, anxiety and depression, and quality of life. Results Fifty-four people responded to the advert, of whom 49 returned completed questionnaires (91%). A further 38 consecutive patients who had a stoma formed for faecal incontinence were identified from hospital records, of whom 20 completed questionnaires (53% response). A total of 69 replies were therefore received. No statistically significant differences were detected between the people recruited via the advertisement and the hospital patients and so the two groups are reported together. Respondents had a median age of 64 years (range 34-88 years). A median of 59 months had elapsed since the operation was performed (range 5-287 months). There were 11 men and 58 women. Respondents were asked to rate their ability to live with their stoma now on a scale of 0-10. The median response was 8 (range 0-10). The majority (83%) felt that the stoma, within the past month, restricted their life “a little” or “not at all”. Comparing the response to two questions about perceived effect on quality of life with a stoma now and with incontinence previously, there was a significant difference (p=0.008, Fisher’s Exact Test, Figure 1). In response to the question “please rate how satisfied you are with having the stoma”, the median response was 9 on a scale of 0-10 (range 0-10). Eighty-four percent would “probably” or “definitely” choose to have the stoma again and only 10% would “probably” or “definitely” prefer to have it closed. Respondents were asked the question “compared to when you were incontinent, how much change has having a stoma made to your overall quality of life”? A scale from –5 to + 5 was given for the response and respondents were asked to circle their answer, where –5 = much worse, 0= same, +5 = much better. The median rating was +4.5 (range –5 to +5, Figure 2). Thirty-four stated that they had required further surgery since the original stoma for incontinence and many had experienced problems such as a hernia or mucus leakage. Despite this, most were very positive about the stoma. Quality of life as measured by the SF-36 was well below population norms, but neither depression nor anxiety (measured by the HAD scale) was a prominent feature, with a few exceptions.

Figure 1: perceived effect on quality of life

0

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Not at all A little Quite a lot A great deal

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Figure 2: How much change has having a stoma made to your quality of life

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Conclusions In this retrospective study of self-selected people who had undergone formation of a colostomy to manage faecal incontinence, the overwhelming majority were positive about the stoma and the difference it had made to their life. However, a few had not adapted and disliked the stoma intensely. While not without risk of complications and management problems, health care professionals should discuss a stoma as an option with patients whose lives are restricted by faecal incontinence. 29 Schraffordt S1, Vervest H2, Bisseling T2 1. Meander Medical Centre, 2. St. Elisabeth Hospital Tilburg THE OUTCOME OF TVT ANALYSED WITH DISEASE-SPECIFIC QUALITY OF LIFE QUESTIONNAIRES: RESULTS FROM THE NETHERLANDS MULTICENTER TVT STUDY. Aims of Study To determine the changes in Quality of Life (QoL) in women with urinary stress incontinence undergoing TVT, assessed with the IIQ-7 and UDI-6 questionnaires. Methods From March 2000 until September 2001 635 women with urinary stress incontinence and without any previous incontinence or prolapse surgery, underwent a TVT procedure as described by Ulmsten et al. (1). Pre- and postoperative data regarding history, physical and urodynamic data were collected prospectively from the 53 participating Dutch gynecologists and urologists according to ICS standards (2). Participating women received the QoL questionnaires prior to and 2, 6, 12 and 24 months after surgery at their home address. The processing of these questionnaires was anonymously and all physicians are blinded to individual results. The response rate is 70%. Disease-specific health-related quality of life questionnaires, the short form Incontinence Impact Questionnaire (IIQ-7) and the short form Urogenital Distress Inventory (UDI-6), were used (3). These questionnaires are translated and validated for the Dutch language and population (4). The UDI-6 is subdivided in three domains or subscales: irritative symptoms, stress symptoms and obstructive/discomfort symptoms. The range in score of IIQ-7, UDI-6 and its domains is from 0 to 100, where a higher score indicates more impact or bother. The scores are also classified as no complaints (scores 0), slightly bothered (scores up to 33), moderately bothered (scores from 33 to 67) or greatly impaired (scores from 67 to 100).

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Table 1. Pre- and Postoperative QoL scores preoperative postoperative 2 months 6 months 12 months 24 months IIQ-7 58 ± 21 (57) 15 ± 22* (5) 12 ± 19* (0) 11 ± 18* (0) 12 ± 20* (5) UDI-6 58 ± 19 (55) 25 ± 19* (22) 24 ± 18* (17) 22 ± 18* (17) 23 ± 20* (22) UDI domains irritative 66 ± 26 (67) 32 ± 25* (33) 30 ± 25* (33) 28 ± 24* (33) 30 ± 25* (33) stress 75 ± 19 (83) 16 ± 23* (0) 14 ± 21* (0) 13 ± 20* (0) 16 ± 22* (0) obstructive 31 ± 29 (33) 27 ± 24 (17) 24 ± 23* (17) 23 ± 23* (17) 24 ± 23* (17) data represent mean ± standard deviation with median value in brackets. * Statistically significant differences between pre- and postoperative values (p < 0.01, Wilcoxon Signed-Rank test).

Results The results are listed in table 1. There is a 65% follow-up of all patients at 24 months. There is a statistically significant decrease in IIQ-7 and UDI-6 scores, indicating a clinically relevant decline in the impact respectively bother of stress incontinence. The median scores indicate that most of women have either no complaints or are slightly impaired only. Improvement in IIQ-7 respectively UDI-6 were observed in 93% and 92% of women, scores remained equal in 2% (IIQ-7) and 3% (UDI), while in both in 5% the scores indicate a worsening of the impact and bother of stress incontinence. From the UDI subscales it becomes obvious that women with stress incontinence have considerable irritative symptoms prior to TVT, but they disappear significantly. This phenomenon was also observed by Vassallo et al. who used the same QoL instruments (5).

The subscale stress incontinence shows a tremendous decline in score and alleviation of the primary complaint. Improvement in this score was seen 94% of women, while the score remained equal in 4% and worsened in 2%. These values are in accordance to the cure rate of 86% that women report to their physician. There are no major changes in the subscale obstructive symptoms after 2 months, but the values are significantly lower after 6,12 and 24 months, indicating a more easier voiding over time. Conclusions Objective cure rates of stress incontinence surgery are often determined by physical examination, pad tests or urodynamic investigation. These investigations only reflect the continence state at that single moment in time. A Quality of Life analysis provides different information over a longer period in time and shows perhaps more sensitive the outcome of incontinence surgery. It may therefore more accurately reflect the true effect of TVT. These results indicate a clinically important improvement of Quality of Life and cure of stress urinary incontinence after TVT. References 1. Ulmsten U, Henriksson L, Johnson P, Varhos G. Int Urogynecol J 1996;7: 81-86. 2. Abrams P, Cardozo L, Fall M, et al. Neuro Urodyn 2002;21:167-178. 3. Uebersax JS, Wyman JF, Shumaker SA, McClish DK, Fantl JA, et al. Neuro Urodyn 1995;14:131-

139. 4. Vaart van der CH, Leeuw de JRJ, Roovers JPWR, Heintz APM. Neuro Urodyn 2003;22:97-104. 5. Vassallo BJ, Kleeman SD, Segal JL et al. Obstet Gynecol 2002;100:518-24.

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30 Robinson D1, Anders K1, Cardozo L1, Bidmead J 1 1. Dept of Urogynaecology, Kings College Hospital CURE: DO CLINICIANS KNOW BEST? Aims of Study The concept of cure is difficult to interpret. Subjective cure is the resolution of clinical symptoms whereas objective cure describes the outcome of repeat evaluation. Whilst symptomatic improvement is clearly the aim of intervention in lower urinary tract dysfunction this provides a qualitative rather than quantative assessment and is more difficult to measure. There is no consensus of opinion regarding which is more important (1). Subjective change and improvement in QoL were rated most highly in a recent survey of patients and clinicians (2) and the patient’s concept of cure has previously been reported (3). The aim of this study was to determine what clinicians regard as ‘cure’ and which outcome measures they used both in research and clinical practice. Methods Members of ICS (UK) were identified from the mailing list and each was sent a structured questionnaire with covering letter and reply paid envelope. The questionnaire was divided into six sections regarding acceptability of symptoms following treatment, overall treatment expectations and outcome assessment following treatment in everyday clinical practice and also in a research setting. Respondents were also asked to state their profession and what they felt was the most bothersome urinary tract symptom. All responses received within 12 weeks of the mailing date were included in this analysis which was performed using SPSS (V10). Results 299 questionnaires were distributed and 156 (52.7%) were returned completed correctly. The occupation of respondents is shown below [Table 1] OCCUPATION NUMBER (%) Urogynaecologist 33 (21.3) Urologist 29 (18.6) Gynaecologist 21 (13.5) Obstetrician and Gynaecologist 20 (12.8) Physiotherapist 21 (13.5) Continence Nurse 17 (10.9) Continence Advisor 5 (3.2) Geriatrician 3 (1.9) Physician 1 (0.6) Clinical Scientist 1 (0.6) Table 1: Occupation of Respondents Overall 85.9% of responding clinicians felt a good improvement in urinary symptoms so that they no longer interfered with quality of life was a realistic outcome whilst just 3.2% hoped for a complete cure [Table 2]. Unsurprisingly only one respondent hoped for “any improvement, no matter how small”. Sub-group analysis by profession did not show any differences in expectations regarding outcome or acceptability of symptoms following treatment. Complete cure of all bladder symptoms 5 (3.2%) A good improvement so they no longer interfere with your life 134 (85.9%) Being able to cope better so your life is affected less 16 (10.2%) Any improvement in your bladder symptoms, no matter how small 1 (0.6%) Table 2: Overall Expectations Regarding Treatment In general the majority thought that small or infrequent episodes of leakage were acceptable although frequent or large leaks were not. Irritative urinary symptoms such as urgency and urge incontinence were felt to be less acceptable as was frequency and nocturia. The majority of clinicians considered having to

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use pads on an occasional basis was reasonable although constant use of incontinence pads was not. In addition leakage during intercourse was felt to be unacceptable [Table 3]. Overall urinary incontinence (12.3%), urge incontinence (10.7%), urgency/frequency (4.6%) and nocturia (2.6%) were considered to be the most bothersome symptoms. Other responses included; bladder pain, embarrassment and fear. Yes Probably No Never ever leaking no matter what you do 90% 3% 6% Occasional small leak on coughing or sneezing 49% 35% 14% Occasional small leak on strenuous exercise 54% 37% 8% Occasional large leak on coughing or sneezing 3% 19% 76% Frequent small leaks on coughing or sneezing 0% 8% 91% A sudden urge or need to pass water (no leaking) 19% 45% 34% Occasionally leaking before reaching the toilet 7% 40% 51% Having to pass water very often during the day 3% 19% 76% Having to get up once at night to pass water 72% 22% 6% Having to get up twice or more at night to pass water 6% 28% 63% Occasionally having to wear panty liners ‘just in case’ 41% 47% 12% Occasionally having to wear pads ‘just in case’ 18% 42% 39% Having to continue to wear pads most of the time 1% 5% 92% Leaking during sexual intercourse 4% 19% 77% Table 3: Acceptability of Symptoms following Treatment In general outcome assessment was more rigorous in research when compared to clinical practice. In the research setting 61% felt both subjective and objective measures should be used as assessment of treatment whilst in clinical practice 42% thought subjective improvement alone, and 36% subjective improvement in QoL, were appropriate. Few clinicians were routinely using pad testing alone and few used objective measures in clinically [Table 4]. RESEARCH CLINICAL Subjective improvement in symptoms 7.7% 42.6% Subjective improvement in QoL 8.3% 36.1% Objective cure on urodynamic testing 1.9% 0.6% Objective cure on pad testing 3.2% 1.3% Subjective (QoL) and objective (urodynamic) cure 17.9% 4.5% Subjective (QoL) and objective (pad test) cure 30.1% 11.6% Subjective (QoL) and objective (urodynamic/ pad test) cure 30.8% 3.2% Table 4: Assessment of Outcome Conclusions There is no common consensus regarding the concept of ‘cure’ or the methods of assessing outcome following treatment. Our findings show that most clinicians are realistic in their expectations following treatment and pragmatic in their assessments of cure. Equally there would appear to be a consensus of opinion across specialties when considering cure and its definition. Whilst subjective and objective assessments are felt to be appropriate in a research setting subjective outcomes are used more commonly in clinical practice. As part of our on-going research into the concept of cure we hope to compare the expectations of clinicians and patients when evaluating outcome. Reference 1. Neurourol Urodynam 1998 17: 249. 2. Int Urogynaecol J 2002 13: 96. 3. Neurourol Urodyn 2002 21(4): 429-430.

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31 Tubaro A1, Prezioso D 2, Zattoni F 3, Artibani W 4, Pesce F 4, Scarpa R M5, Simoni L 6 1. Sant'Andrea Hospital, 2. Policlinico Federico II, Naples - Italy, 3. (Az. Ospedaliera S. Maria della Misericordia, Udine -Italy, 4. Policlinico G. Rossi, Verona - Italy, 5. Ospedale di Orbassano, Torino- Italy, 6. MediData Studi e Ricerche, Modena - Italy THE FLOW STUDY: VALIDATION OF FOUR QUESTIONNAIRES ON SYMPTOMS AND QUALITY OF LIFE IN ITALIAN WOMEN WITH LUTS Aim of Study No validated questionnaires are available for assessing symptoms and quality of life (QOL) in Italian women with LUTS. More in general, little is known about the impact of LUTS and the related bother on QOL in women. In the context of a large multi-centre observational study of women with LUTS (FLOW- Female LUTS: Observational Study in Women), we translated into Italian and validated three female-specific questionnaires: 1) ICIQ-LF Female [the long form of the ICI questionnaire]; 2) ICIQ-SF [the short form of the ICI questionnaire]; 3) UDI [the Urogenital Distress Inventory]. Moreover, we tested whether a modified version of IPSS [the International Prostate Symptom Score] can be applied to women. In it, the QoL single question refers to urinary symptoms generically, in spite of the specific reference to prostatic disease of the original IPSS. This new version was named W-IPSS [Women IPSS]. Methods The validation process consisted of the following steps: forward and backward translation, test of comprehension, discriminant validity (i.e., the ability of the questionnaire to discriminate between healthy and ill subjects) and test-retest reliability (i.e., stability of responses over a short period). We translated questionnaires into Italian following the standard procedure, as detailed in Knudsen et al (2000). The comprehension of questionnaires was tested by interviewing women after they had filled in the questionnaires. A comprehension rate was built for each questionnaire as the percentage of correctly understood questions and pre-coded answers of all items by all patients. A case-control study was then performed. Cases were defined as women aged 18 year affected by LUTS from at least 3 months and with negative dipstick. Controls were defined as healthy women of comparable age. All women were enrolled consecutively. Both cases and controls filled in two questionnaires (Table 1). In order to evaluate reliability, cases were retested after 7 days and a correlation analysis was performed between the first and the second measurement (Pearson’s r). Discriminant validity was assessed by comparing the scores of cases and controls with ANOVA.

Table 1 – Sample size for each questionnaire

ICIQ- LF ICIQ- SF UDI W-IPSS Comprehension 15 10 10 15 Cases – Visit 1 (Retest) 71 (69*) 50 (46*) 54 (53*) 75 (74*) Controls 81 50 56 83

*Questionnaires available for test-retest analysis Results In general, 93.5% of items were easily and correctly understood by patients. The average test-retest correlation coefficient ranged between 0.75 for UDI and 0.86 for ICIQ-SF. Correlation coefficients were statistically significant for all questionnaires items. The questionnaires were generally able to discriminate between healthy and ill subjects. For ICIQ-LF the comprehension rate was 99.4%. Four out of 16 patients did not understand “hesitancy” (item 30) correctly: therefore it was retranslated into Italian. The average test-retest correlation coefficient between ratings was 0.84 and was greater than 0.9 for more than 15 items (p<0.0001 for all). Distribution of responses was statistically (p<0.001) different in cases and controls, with the exception of sexual matters and QOL related to daily activities. ICIQ-SF was well understood by all patients, with a comprehension rate of 99.1%. A high and significant correlation between ratings was also observed: r ranged from 0.91 to 0.94 (p<0.0001) for items 3 (frequency of leakage), 4 (quantity), 5 (impact on daily life), while being lower (0.64) for item 6 (circumstances of leakage). Cases and controls were discriminated at ANOVA (p<0.001).

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As far as UDI is concerned, “daytime frequency”, “urgency”, “incontinence”, “incomplete voiding” and “push on vaginal walls to have bowel movement” were found difficult to understand by patients (2 subjects out of 10). The average test-retest correlation coefficient was 0.8 for symptoms (p<0.001) and 0.72 for its associated bother (p<0.001). The presence or absence of symptoms discriminated healthy from ill patients. Finally, in W-IPSS two items were difficult to understand for more than 25% of cases (“intermittency” and “nocturia”). The average test-retest correlation coefficient between ratings was 0.76 (p<0.0001). “Intermittency” had the weakest correlation coefficient (r=0.57). ANOVA differentiated cases from controls at all items.

Conclusions These data of the validation process of the 4 questionnaires show that they are generally easy to understand, and have a good to excellent reliability and a high discriminant validity. Overall, the questionnaire with the best psychometric properties appears to be the ICIQ both in the long and short form. The validation process is still in progress. Further analyses are planned in order to test internal consistence, construct validity (by comparing questionnaires to uroflowmetry, voiding diary and SF-36) and sensitivity to change (by rating questionnaires again after a 1-year follow up).

Reference Knudsen HC, Vazquez-Barquero JL, Welcher B, Gaite L, Becker T, Chisholm D, Ruggeri M, Schene AH, Thornicroft G (2000). Translation and cross-cultural adaptation of outcome measurements for schizophrenia. EPSILON Study 2. European Psychiatric Services: Inputs Linked to Outcome Domains and Needs. Br J Psychiatry Suppl 2000;(39):s8-14. 32 De Wachter S1, Wyndaele J J1 1. Department of Urology, Faculty of Medicine, University of Antwerpen EXPLORING THE USE OF FREQUENCY-VOLUME CHARTS Aims of Study Frequency-volume charts are an important tool in the investigation of patients with lower urinary tract (LUT) dysfunction, because they provide the ability to study LUT function during normal daily activities. The information obtained by frequency-volume charts is currently limited to the number of voidings, the voided volumes, the distribution of voidings between daytime and nighttime, the registration of episodes of urgency and leakage and the number of incontinence pads used. Little research has been done to incorporate a sensory evaluation into these charts. However adequate sensation of bladder filling is important for a proper bladder function. Currently, sensory information related to bladder filling is mainly deducted from cystometric studies in which patients have to be catheterized and in case of conventional cystometry, the bladder is artificially filled. To what extent these factors confound the sensory evaluation remains unknown. Therefore we studied whether frequency volume charts can be used as a non-invasive tool for sensory evaluation. Furthermore we studied the agreement between sensory data derived from these charts with those obtained during conventional cystometry. Methods Fifteen healthy female nulliparous students without urological history between 18 and 24 years old were asked to fill out a 3 day frequency-volume chart during normal daily activities. They noted the time and volume of each micturition and scored the grade of perception of bladder fullness according to predefined grades before each micturition (table 1). All volunteers also underwent a conventional cystometric bladder filling at 30 mL/min and were asked to describe all sensations related to bladder filling. Furthermore they correlated these sensations to the same predefined grades of perception of bladder fullness that was used on the frequency-volume charts.

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Table 1 No desire to void 0 No bladder sensation

1 First sensation of bladder filling Voiding can easily be delayed for more than 60 minutes

Desire to void

2 First desire to void Voiding can be delayed for at least 30 minutes

3 Strong desire to void Voiding cannot be delayed for more than 15 minutes

4 Urgent desire to void Voiding cannot be delayed for more than 5 minutes

Results In total, 326 micturitions were recorded during daytime. These data are presented in table 2.

Table 2 Grade of bladder fullness

Mean ± SD(mL)

95% CI (mL)

Range (mL)

Number (%)

0 110 ± 59_ _95 – 126 _10 – 300 18.7 1 206 ± 94_ 190 – 221 _10 – 500 46.3 2 303 ± 105 280 – 325 100 – 650 25.5 3 402 ± 133 353 – 448 200 – 650 9.5 4 / / / 0

The voided volumes between the different grades of perception of fullness were significantly different ( P < 0.001). Moreover, the grade of perception of bladder fullness was positively correlated with the volume voided (Rs 0.67, P < 0.001). Sixty-five percent of the voidings was graded without desire to void (grade 0 and 1), whereas only 9.5% of the voidings was graded as strong desire to void (grade 3). No volunteer reported an urgent desire to void (grade 4). During cystometry, all volunteers reported three different sensations of filling. First sensation of filling was described at 190 ± 88 mL (95%CI: 176-204mL, range 22-321mL), first desire to void at 268 ± 117 mL (95%CI: 243-293mL, range 128-509mL) and strong desire to void at 410 ± 145 mL (95%CI: 358-463mL, range 273-715mL). The mean volumes for the different sensations of bladder fullness on the charts and during cystometry were not significantly different (P > 0.2). This is shown in the figure. The mean differences respectively were 16 mL for grade 1; 34 mL for grade 2; 10 mL for grade 3.

Conclusions Data from our pilot study, which explored the use of frequency-volume charts in healty female students, show that the information obtained from these charts can be extended beyond just recording “classical” parameters such as voided volumes: these charts can be used as a non-invasive non-expensive tool to

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evaluate sensations of bladder filling during normal daily activities. Moreover sensory data deducted from frequency-volume charts show a good agreement with sensory data from cystometric bladder filling. Because the largest part of the micturitions was made without a desire to void in the healthy female population we studied, the distribution of sensation-related micturitions may provide a new parameter to study bladder behaviour. Including a sensory evaluation into frequency-volume charts and evaluating the distribution between sensation and non-sensation related micturitions may improve the power of these charts to discriminate between different pathologies. The use of these “sensation-related frequency-volume charts” is currently investigated in different groups of incontinent patients. 33 Dmochowski R1, Heit M2, Sand P3 1. Vanderbilt University, 2. University of Louisville, 3. Northwestern Medical School THE EFFECT OF ANTICHOLINERGIC THERAPY ON URGENCY SEVERITY IN PATIENTS WITH OVERACTIVE BLADDER: CLINICAL ASSESSMENT OF A NEWLY VALIDATED TOOL Aims of Study Most epidemiological studies of overactive bladder (OAB) have focused on urge urinary incontinence and its prevalence, often overlooking 24-hour frequency and urgency, the more common symptoms of the disorder. 16,000 surveyed subjects indicated that urgency and 24-hour frequency are more prevalent in individuals between the ages of 35 and 55 years. Specifically, 17% of respondents reported having OAB symptoms with 14% reporting 24-hour frequency, 9% urgency and 6% urge urinary incontinence.1 While treatments are available for the indication of OAB, few trials have looked at the impact of treatment on the prevalence of urgency, largely due to the lack of a validated metric for urgency severity quantification. Trospium chloride, a quaternary amine, is an antimuscarinic agent that has been a leading treatment for OAB in Europe over 20 years. The objective of this study was to determine the effects of trospium vs. placebo on the severity of urgency associated with OAB in patients with predominant urge urinary incontinence as part of a 12 week efficacy and safety study. Methods This was a parallel, randomized, double-blind, placebo-controlled trial in patients with OAB. Symptoms of urgency, >10 voids per day and >1 urge urinary incontinence episode per day were required for inclusion. Participants received either trospium chloride 20 mg bid or placebo for 12 weeks following a 3-week washout and completion of a 7-day baseline bladder diary to record each void, urgency severity, and urge urinary incontinence episode per day. The 7-day bladder diary included the validated Urgency Severity Scale (IUSS)2 which asks patients to rate the urgency severity prior to toileting where:

0: NONE - no urgency 1: MILD - awareness of urgency, but easily tolerated 2: MODERATE - enough urgency discomfort that it interferes with usual activity/ tasks 3: SEVERE - extreme urgency discomfort that abruptly stops all activity/tasks Treatment effects were measured at weeks 1, 4 and 12. Change in urgency severity, urge frequency per 24 hours, urinary frequency per 24 hours, and number of urge urinary incontinence episodes per 24 hours from baseline, were our outcomes of interest. Efficacy analyses were done using the intent-to-treat sample and the last observation carried forward data set. ANOVA models or where appropriate, rank ANOVA were used. Results 523 patients were studied at 51 sites (262 trospium /261 placebo). The mean age was 62 years and 74% were female. The most frequently reported adverse events were dry mouth and constipation. 24-hour frequency and urge urinary incontinence episodes per day were significantly reduced starting at week 1 and persisted through week 12. 3

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Mean Change from Baseline*

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trospium (n=253)

placebo (n=256)

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placebo (n=256)

Baseline 1.77 1.77 11.29 11.72 p=0.88 p=0.11 *Week 1 -0.11 -0.01 -1.13 -0.71 p=0.003 p=0.06 *Week 4 -0.18 -0.06 -2.10 -1.00 p=0.004 p<0.0001 *Week 12 -0.22 -0.04 -2.30 -1.08 p=0.0001 p<0.0001

Conclusions Trospium-treated patients moved from having, on average, a moderate degree of urgency with each toilet void toward experiencing a mild sensation of urgency with each void, whereas, placebo-treated patients had no notable change. In addition, trospium was found to be effective in reducing the average urge frequency, 24-hour frequency and urge urinary incontinence episodes per 24 hours in patients with OAB in comparison to placebo. Trospium was also well tolerated. References 1Milsom I, Abrams P, Cardozo L, et al. How widespread are the symptoms of an overactive bladder and how are they managed? A population-based prevalence study. Br J Urol Int 2001 Jun; 87(9):760-6. 2Copyright 2003, all rights reserved. 3Zinner N, Gittelman M, et al. Trospium Chloride Improves Overactive Bladder Symptoms: A Multicenter Phase III Trial (Abstract). Annual American Urological Association Meeting, Chicago, IL, April 26, 2003. 34 Weston R1, Das S2, Pace A2, Powell C2 1. Wirral NHS Trust, 2. Countess of Chester Hospital PROSPECTIVE COMPARISON OF FREE FLOW RATE WITH FLOW RATE OBTAINED FOLLOWING FLEXIBLE CYSTOSCOPY Aims of Study In the investigation of lower urinary tract symptoms many cases can be reliably assessed from a good history and a simple measurement of maximum flow rate (Q-max) alone. To obtain a reliable flow rate patients must void a reasonable volume, as flow is dependent on voided volume [1]. Clinical trials have demonstrated that the reliability of Qmax can be improved by bladder instillation of a fixed volume [2], however it is not generally acceptable to catheterise a patient purely to obtain a urinary flow. Many patients being investigated for lower urinary tract symptoms will require a flexible cystoscopy along with uroflowmetry as part of their work up. This study compares simple uroflowmetry of men before and after flexible cystoscopy. Methods A prospective sample of eighty men attending for diagnostic flexible cystoscopy were consented and recruited for the study. Patients were initially asked to perform uroflowmetry using a Dantec Menuet flowmeter. Cystoscopy was then performed using a 17 French Olympus CYS3 cystoscope. At the end of the procedure the patient’s bladder was filled with water until they felt the desire to void, the cystoscope was withdrawn and the patient performed a further void into the same uroflowmeter. All uroflowmeter printouts were manually read. Patients were excluded if they were noted to have a urethral stricture, or if their uroflowmetry trace suggested bladder sphincter dyssynergia. The data was analysed using the Students paired sample t-test (two-tailed). Statistical significance was assumed with a p value <0.05.

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Results Of the eighty men five were excluded for the reasons given above. The mean age was 62 years (+14.6SD) range 27-88 years. Table 1 demonstrates the results obtained along with the p values. There was no statistical difference between the variables of Qmax and Qave in the pre and post cystoscopy uroflowmetry. A statistically significant increase in post cystoscopy voided volume was noted (p < 0.031). Plotting the results on a scatter graph (chart 1) demonstrates a linear relationship for Qmax when comparing the pre and post cystoscopy values. Pearsons test showed a statistically significant correlation between pre and post Q-max (R2 = 0.615) and Q-ave (R2 = 0.557). Table 1 mean +SD of variables pre and post cystoscopy.

Mean + SD Pre cystoscopy Post cystoscopy

Significance

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Qmax mls/s 14.8 + 7.1 14.9 + 7.1 p = 0.85 R2 = 0.615 Qave mls/s 8.0 + 4.3 8.3 + 4.0 p = 0.44 R2 = 0.557 Void vol mls 255 + 132 290 + 117 p = 0.031 nil

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Chart 1. Pre and post cystoscopy Qmax Conclusions Previous studies have looked at the effects of urethral instrumentation on uroflowmetry with conflicting results. It is widely accepted that multiple free flow studies are more useful than a single result especially if clinical management or the need for subsequent pressure flow studies is based on the result. The aim of this study was to investigate our practice of performing uroflowmetry after diagnostic flexible cystoscopy compared to free uroflowmetry. Our results suggest that flexible cystoscopy and bladder filling prior to uroflowmetry does not significantly affect the Qmax or Qave, however it does produce a higher voided volume. The results demonstrate a degree of individual patient variability between subsequent voids, which is widely recognised. We are not advocating the use of a cystoscope purely to fill the bladder, however we suggest that this method can be used to produce clinically comparable results when uroflowmetry is required. The benefit of this method is that in patients who require a flexible cystoscopy and a free flow, additional appointments at uroflow clinics are avoided, and patients who have trouble attending clinic with a suitably filled bladder can have free flows easily performed. [1] Abrams et al. BJU 1995; 76(1): 11-15 [2] Yukio et al. Int J Urol 1995; 2: 322-325

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35 Artibani W1, Pesce F1, Rubilotta E1, Aresu L1, D'Amico A1, Curti P1, Cerruto M A1 1. Dept. Urology Policlinico - Verona HOW UROFLOWMETRY IS PERFORMED: RESULTS OF AN INTERNATIONAL SURVEY AMONG ICS MEMBERS Aims of Study To assess the modalities of performing and interpreting uroflowmetry (UF) by International Continence Society (ICS) members worldwide. Methods A questionnaire on UF was delivered by e-mail to the members of ICS involved in UF in their practice. This 11-item questionnaire concerned: the professionals actually performing the test, the number of UFs for each subject in a single session, the lower and upper limits for considering suitable the voided volume (VV), the use of UF nomograms and the parameters considered for the interpretation of UF. Other questions regarded the means of measuring post-void residual (PVR) and the Qmax cut-off for an abnormal UF. Results One hundred and sixty-six centers from 35 countries in 4 continents completed the questionnaire and returned it to the Authors. Most of the respondents were urologists (81/166, 48.8%) and urogynaecologists (53/166, 31.9%). UF is performed by nurses in 85/166 centers (51.2%), by physicians in 49/166 (29.5%) and by both in 31/166 (16.7%). UF is performed only once in 54/166 centers (32.5%), more than once (usually twice) in 42/166 (25.3%) and more than once only in particular cases in 70/166 (42.2%). In most centers (91/166, 54.8%) the minimum VV considered suitable for the UF interpretation is 150mL; other common lower limits are 100mL (26/166, 15.7%) and 200mL (23/166, 13.8%). Regarding the maximum VV, the respondents were mainly divided between 500mL (52/145, 35.8%) and any volume (57/145, 39.3%). Regarding the interpretation of UF, nomograms are not used by 117/166 respondents (70.5%) because they are considered useless (30, 25.6%) or because clinicians prefer to base the judgement on their own experience (60/117, 51.3%). Of the 49/166 centers (29.5%) using UF nomograms for interpretation of the results of UF, 21/49 (42.9%) do so in every case, 28/49 (57.1%) only under particular circumstances. The UF nomogram most commonly used is the Liverpool nomogram (21, 42.9%), with the Siroky nomogram being used considerably less frequently (7, 14.2%). Table I shows a summary of data concerning the parameters used for UF interpretation. When the use of a cut-off for defining an abnormal Qmax was indicated (83 centers), this varied between 8 and 30mL/sec: 15mL/sec in 46.9%, 10mL/sec in 22.9% and 12mL/sec in 14.4%. Parameters VV Qmax Qave PVR Shape Gender Age Centers (n=161)

117 72.6%

124 77.0%

37 22.9%

83 51.5%

117 72.6%

74 45.9%

76 47.2%

Table I: parameters considered for UF interpretation. In 81.9% of the centers (136/166) PVR is always measured, by means of ultrasounds (conventional or with a bladder-scan) more commonly than with a catheter (63.75% vs 36.25%). In reading Qmax, 112/155 (72.3%) respondents stated that they use the corrected value directly on the flow curve, while 43/155 of them (27.7%) consider the number automatically generated by the flowmeter. Conclusions This international survey showed that there is only a partial concordance in the methods of performing and interpreting UF. In fact, there is a high concordance in the minimum VV considered suitable for the UF interpretation, the measurement of PVR and the evaluation of Qmax as the corrected value read on the flow curve, while there is a low concordance on two important aspects: the number of flows performed for each evaluation and the value of Qmax cut-off. Moreover, in more than 30% of the centers only 1 UF is performed, although it has been recently recommended to achieve at least 2 UFs (1) and to always measure and provide the PVR when reporting UF results (2), which is not the case in 18% of the sample. The parameter most commonly considered in the interpretation of UF is the Qmax, but the value of its cut-off is rather variable among the centers, which can lead to divergent results. Most of the clinicians seem not

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to employ objective tools for UF interpretation, such as nomograms but are rather guided by personal experience. In conclusion, the findings of this survey suggest a need for a more thorough standardization of UF in order to achieve a more comparable evaluation of this apparently simple examination. References Abrams P., Cardozo L., Khoury S., Wein A. Incontinence, 2nd edition, Health Publication Ltd 2002, pp 342 Schafer W., Abrams P., Liao L., Mattiasson A., Pesce F., Spangberg A., Sterling A.M., Zinner N.R. and Van Kerrebroeck P.: Good urodynamic practices: uroflowmetry, filling cystometry and pressure-flow studies. Neurourol Urodyn, 2002; 21(3):261-274 36 Dixon A1, Anders K1, Cardozo L1, Robinson D1 1. Kings College Hospital SATISFACTION GUARANTEED? THE URODYNAMIC EXPERIENCE Aims of Study Urodynamics remains the investigation of choice for women with lower urinary tract dysfunction. There is an assumption that the test is intrusive and invasive leading to patient anxiety and dissatisfaction (1). The role of urodynamic investigation remains controversial and there is continued debate (2), (3) regarding their use prior to treatment in women with lower urinary tract symptoms. This is particularly relevant when conservative management is planned. However these debates often do not include the patients’ preference to have the opportunity for a definitive diagnosis before treatment commences. In view of this, and as part of ongoing departmental audit, we chose to look at patient satisfaction with particular reference to the acceptability of these invasive investigations. Methods Women were recruited prospectively from a one-stop urodynamic clinic in a tertiary referral Urogynaecology Unit. All complained of troublesome lower urinary tract symptoms and had been referred for further investigation and management. All women underwent videocystourethrography and were then asked to complete a structured satisfaction questionnaire including questions related to provision of information and questions concerning fears, anxieties and well-being throughout the procedure. Results In total 100 consecutive women, aged 18 –80, were recruited over a two-month period and 78 (78%) questionnaires were completed and returned. The majority (54%) were referred by their GP and in 76% of cases this was their first visit [Figure 1]. Figure 1: Source of Patient Referral

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Most women (86%) received written information regarding the investigation prior to arrival; 90% found this accurate and 98% found it helpful. Prior to the investigation 90% of women felt they had adequate time to discuss their urinary symptoms and 95% felt the test had been fully explained. During the procedure 87% felt staff were sensitive to their fears and anxieties, 92% felt safe and comfortable and 93% had adequate privacy [Figure 2]. Afterwards 91% felt their results were fully discussed and 83% had a treatment plan formalized. The overall satisfaction rate was 92%.

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Figure 2: Perceptions of the Investigation Conclusions Despite the invasive and intrusive nature of the investigation our findings would suggest that a one-stop urodynamic clinic offers high levels of patient satisfaction in addition to providing an efficient, patient orientated service. The majority of women find the investigations acceptable and worthwhile. To complete the audit cycle and maintain standards within the department we aim to re-audit the service in the near future with a particular emphasis on patient needs and expectations.

References 1.Neurourol Urodynam 1997 16(5): 509 –510 2.Proceedings of 26th International Urogynaecology Association Meeting. Melbourne, Australia. December 2001. 3.Proceedings of 7th International Continence Society (UK). Belfast, UK. April 2000. 37 Bycroft J1, Wood S 2, Bywater H2, Knight S2, Craggs M2, Shah J1 1. Institute of Urology & Nephrology, 2. Spinal Injuries Unit, Stanmore ACCEPTANCE AND MORBIDITY ASSOCIATED WITH URODYNAMIC STUDIES IN PATIENTS WITH SPINAL CORD INJURY. Aims of Study Spinal cord injury (SCI) results in profound alterations to the urinary tract, resulting in significant patient morbidity. Urodynamic studies are important in determining the most favourable treatment strategies in patients with SCI [1]. Several studies have looked at the tolerability [2] and morbidity [3] associated with urodynamic investigation in non-SCI individuals, however little data is available regarding acceptance and complications in patients with SCI. The aim of our study was therefore to investigate acceptance and morbidity related to urodynamic studies in patients with spinal cord injury.

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Methods 41 patients who underwent urodynamic testing in our unit were included in the study; the study was completed by 37 (25 male, 12 female). Of these, 19 patients had complete injuries and 18 had incomplete injuries. 19 (51%) principally used intermittent self-catheterisation (ISC) to manage their bladder, 9 (24%) reflex-voided, 6 (16%) used suprapubic catheters (SPC). Other methods of bladder emptying were voiding on urge, strain voiding and sacral anterior root stimulation (one of each). Patients continued their normal medications before and after the study. Dipstick urinalysis was performed prior to urodynamic testing; the sample was sent for microscopy and culture if leucocytes, nitrites or blood were present. Only one patient (with persistent vesico-ureteric reflux) received antibiotic prophylaxis, in accordance with our unit protocol. Patients were given a short questionnaire to complete 7 days after their examination. 37 patients responded to the study questionnaire; 35 (95%) of questionnaires were completed fully. The areas addressed included patient experience of the investigation, the development of urological symptoms in the 7 days post-testing (that were not their previously), and whether autonomic-dysreflexia symptoms were encountered during testing. Patients were asked to provide a urine sample in the week following the test if they thought they had developed a urinary tract infection (UTI). Results 21/41 patients (51%) had abnormal urinalysis prior to urodynamic testing, and 11/21 (27% of all patients) had pyuria and significant bacterial growths. 28 patients (78%) found the test comfortable, 7 (20%) experienced discomfort (6 of whom were incomplete injuries) and 1 patient (who had an incomplete injury) experienced pain. 27 patients (75%) were not embarrassed by the testing, 8 (22%) were slightly embarrassed, and only 1 was very embarrassed. Overall, the majority (22 (61%)) found the test ‘as expected’, 13 (36%) found it ‘better than expected’, and only 1 found it ‘worse than expected’ (see Figure 1). 8 patients experienced symptoms of autonomic dysreflexia during the tests. This represented a third of patients with lesions at T6 and above (who are most susceptible to autonomic dysreflexia). 7 described their symptoms as mild, 1 as moderate and none as severe, and all settled with conservative measures. New symptoms that developed within a week of urodynamic testing are shown in Figure 2. 4 patients (9%) thought that they had developed a UTI following the test, however only 2 patients provided urine samples for analysis. Of these 2 samples, both were culture-positive, however pyuria was only present in 1. Samples in both patients that were taken prior to the test had grown significant numbers of bacteria, but not contained significant numbers of red or white blood cells.

Figure 1: Patients' experiences ofurodynamic testing

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Conclusions Urodynamic studies contribute greatly towards the urological management of spinal cord injured patients [1]. We have established that the examination is acceptable to SCI patients and well tolerated, and meets or exceeds their expectations. Discomfort and pain are more likely to occur in incomplete injuries. Symptoms of autonomic dysreflexia occur in a third of susceptible patients, but are generally mild. This result concurs with previous studies [4]. Patients frequently develop new (albeit mostly transient) symptoms following the study, the commonest of which are increased urinary frequency, increased leakage, increased spasms and cloudy urine. Patients should therefore be informed that they may be symptomatic following urodynamic testing. The cause of new urinary symptoms in non-SCI patients following urodynamic tests are thought to be mainly mechanical, rather than being related to UTI [5]. Whether UTI was the cause of new symptoms in our patient group is unknown. Interpretation is difficult due to the high incidence of asymptomatic UTI (27%) prior to testing. The value of antibiotic prophylaxis in urodynamic testing is still undetermined [6], and should be subject to a larger randomised control trial. We are currently investigating the aetiology of post-urodynamic symptoms. 1.Wyndaele JJ. Spinal Cord 1997: 35(4):213-216. 2.Kortmann BB et al. BJU Int 1999: 84(4):449-453. 3.Brostrom S et al. Int Urogynecol J Pelvic Floor Dysfunct 2002: 13(3):182-184. 4.Giannantoni A et al. Spinal Cord 1998: 36(11):756-760. 5.Coptcoat MJ et al. Br J Urol 1988: 61(4):302-303. 6.Darouiche RO et al. J Hosp Infect 1994: 28(1):57-61. 38 Otcenasek M1, Halaska M1, Krcmar M1, Blovsky J1 1. FN Na Bulovce ADVANCED 3D MODELLING – SIMULATION OF SQUEEZING AND VALSALVA MANOEUVRES IN HEALTHY NULLIPAROUS WOMEN. Aims of Study MRI based 3D modelling is an established diagnostic tool that significantly improves our understanding of the pelvic floor anatomy. To help us with the precise understanding of the pelvic floor function, not only static, but also dynamic models need to be created. We attempted to make a precise 3D model of all important organs of the female pelvis and to simulate their movements and changes of their shape during voluntary squeezing and during Valsalva manoeuvre. Because all MRI scanners work with universal system of coordinates, different scans can be combined and their position reconstructed in a computer model. The acquisition of data for static reconstruction takes long time (minutes). On the contrary, the women can not hold Valsalva or squeeze for more than a few seconds.

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To overcome this problem, we examined six defined planes dynamically (with short time of acquisition of each image) and combined the data with the static model later in the computer. Methods Four healthy nulliparous women were involved in our study. Mean age was 23.4 years (SD 1.9), mean BMI 24 (SD 2.6). They did not complain of any of the lower urinary tract symptoms. A routine gynecological examination did not reveal any abnormal finding. Because we planned to perform the dynamic examination of different planes consecutively (not during one exercise – the woman had to repeat the manoeuvre for each plane separately), it was necessary to ensure good reproducibility of the manoeuvres. This was performed during the initial visit, when the proper squeezing and Valsavla manoeuvre was explained and taught under control of ultrasound. The bladder was filled with 250 ml of sterile saline and a small rectal balloon catheter (7 mm diameter of the balloon) was inserted into rectum to monitor intrarectal pressure. A very good reproducibility of both manoeuvres was achieved (monitored by the position of the uretrovesical junction a by the intrarectal pressure curves). The MRI examination was performed with the Siemens Impact scanner (1.5 T, pelvic phased-array coil). The bladder filling and rectal catheter was the same as during the training (see above). For the purposes of the static 3D modelling, we scanned three sets of images (T2-weighted, slice thickness 3 mm, gap 0.9 mm). First, axial images from the uterine fundus to the most distal muscle fibres of sphincter ani muscle. Second, frontal images from the sacral bone to the upper pole of the symphysis. Third, a special set perpendicular to the axis of the anal canal. We used the three sets to eliminate the partial volume artefact, which can produce major inaccuracies when the model is created from one dataset only. A standard method of 3D modelling was used (1). For the dynamic examination, we used six planes - three semi-frontal (P, Q, R), one sagittal (B) and two parasagittal (A, C) - figures 1, 2. The planes were chosen to cover the different parts of the bladder base and of the levator ani muscle as most distinct structures seen on the dynamic scans. For each plane, the woman performed following sequence of pelvic floor exercise - rest (5 seconds), squeezing - (6 seconds), relaxation (5 seconds), Valsava (8 seconds). The whole sequence of manoeuvres was scanned (time of acquisition 0.81 s, gap 0). For rest, squeezing and Valsalva one image from each plane was chosen, that showed stable value of maximal intrarectal pressure during its acquisition (+-3 cm H2O). The outlines of the visible organs representing different states of the pelvic floor in each plane was imported into the 3D models and the original static model was morphed to fit these outlines. Results Four computer models of continent nulliparous women were created. These models precisely demonstrate the anatomy of female pelvis at rest, and fairly precisely simulate the position of involved organs during Valsalva manoeuvre and squeezing. The changes of position and shape of each modelled organ (urinary bladder, urethra, uterus, rectum, vagina, levator muscle, internal obturator muscle, sphincter ani muscle, urogenital diaphragm) is described and analyzed. Specific spatial relationships of neighbouring structures are visualised and their function is discussed from the point of view of different theories of continence (hammock theory, integral theory, pressure transmission theory). Although not directly visualised, the shape and mechanical properties of the endopelvic fascia is estimated and modelled. All structures are presented individually and in groups, both at rest and during movements. Conclusions The small tissue contrast, great variability, significant post mortal changes and muscle relaxation during surgery are factors, which hindered the proper scientific evaluation of the female pelvic floor. Both the structure and function of individual parts of the region were only estimated with the help of different diagnostic tools, none of which had the capacity provide comprehensive information. The use of the magnetic resonance imaging constitutes a new era in urogynecology. Now it is possible to gain clear images of all major pelvic floor structures, construct 3D models of individual patients both at rest and during dynamic manoeuvres. This will help to make a precise diagnosis for each patient and to tailor surgical procedures individually in the near future.

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Figure 1 - location of dynamic planes Figure 2 - location of dynamic planes axial view sagittal view

1) Neurourology and Urodynamics 19(4), 2000, 447-448 39 Dietz H P1, Eldridge A2, Grace M2, Clarke B3 1. RPA Hospital, Sydney, Australia, 2. Queensland Institute of Medical Research, Brisbane, Australia, 3. Royal Women's Hospital, Brisbane, Australia NORMAL VALUES FOR PELVIC ORGAN DESCENT IN HEALTHY NULLIGRAVID YOUNG CAUCASIAN WOMEN Aims of Study Translabial ultrasound is increasingly being used for the assessment of women presenting with pelvic floor dysfunction and incontinence (1,2). However, there is little information on normal values for bladder neck descent, with the two available studies disagreeing widely (3,4). No data has so far been published on mobility of the central and posterior compartment which can now also be assessed by ultrasound (5). This study presents normal values for urethral, bladder, cervical and rectal mobility in a cohort of young, stress continent, nulliparous nonpregnant women. Methods 118 nonpregnant nulliparous Caucasian women between 18 and 23 years of age were recruited for an ongoing twin study of pelvic floor function. Translabial ultrasound assessment of pelvic organ mobility was undertaken supine and after bladder emptying (6,7). The best of at least three effective Valsalva manoeuvres was used for evaluation, with no attempts at standardization of Valsalva pressure. Parameters of anterior compartment mobility were obtained by the use of on-screen calipers; cervical and rectal descent were evaluated on printouts. All examinations were carried out under direct supervision of the first author or by personnel trained by him for at least 100 consecutive assessments. Results The median age of participants in this study was 20 (range 18- 23). Mean body mass index was 23 (range 16.9- 36.7). Of 118 women, 2 were completely unable to perform a Valsalva manoeuvre despite repeated efforts at teaching and were excluded from analysis, as were ten women who complained of urinary stress incontinence, leaving 106 datasets. Average measurements for the parameters ‘retrovesical angle at rest’ (RVA-R) and on Valsalva (RVA-S), urethral rotation, bladder neck mobility, cysto-cele descent, cervical descent and descent of the rectal ampulla are given in Table 1.

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Parameter Mean StD Range

RVA-R 114 10.6 90 -130 degrees RVA-S 145 23.3 100 - 180 degrees Urethral rotation 32.1 23.5 0 - 90 degrees Bladder neck mobility 17.3 8.8 1.2 - 40.2 mm Cystocele descent 13.7 9.4 30.3 - -10 mm Uterine descent 31.5 13.4 59 - 0 mm Rectal descent 8.6 16.1 54 - -22 mm

____________________________________________________________________ Table 1: Ultrasound parameters of pelvic organ mobility in 106 nulligravid, stress continent Caucasian women of 18-23 years of age. Urethral rotation and Bladder neck mobility are calculated by comparing measurements at rest and on Valsalva. Cystocele, uterine and rectal descent signify lowest positions reached on Valsalva relative to the symphysis pubis, with negative measurements implying descent below the symphysis pubis. Conclusions In this large series of young nulligravid women, wide ranges of values were obtained for all parameters of pelvic organ mobility. As regards the central and posterior compartments, the authors are not aware of any other study using modern imaging methods to determine descent in a cohort of healthy nulliparous women. For bladder neck descent on Valsalva, the most commonly reported indicator of anterior compartment descent, the average was 17.3 mm (range 1.2- 40.2 mm). This is markedly higher than a recently reported series (3) on 51 continent nulliparous volunteers of 20-56 years of age (median bladder neck descent 5.1 mm), but closer to a second, smaller series (4) in younger women (mean bladder neck descent 14 mm). The lack of agreement between studies is likely due to differences in methodology (i.e., patient position and bladder filling, Valsalva strength/ standardization, concomitant levator activation). The authors would propose that, in the interests of reproducibility and simplicity, assessments should be standardized to maximize pelvic organ descent. This would imply that translabial ultrasound be performed supine, after bladder emptying, and with careful attention to avoiding levator co- activation. The wide variation in measurements observed in this study implies that there is likely to be a significant congenital contribution to the phenotype of female pelvic organ prolapse. Together with recent work defining the effect of childbirth and delivery on pelvic organ mobility (7), this study supports the concept that pelvic organ prolapse observed in any given woman may be congenital, traumatic or due to a combination of those factors. This may have significant implications for treatment and underscores the potential for a molecular genetic approach to pelvic organ prolapse. References 1 Curr.Opin.Obstet.Gynecol. 1995;7:382-85. 2 Curr.Opin.Obstet.Gynecol. 1997;9:313-16. 3 Int.Urogynecol.J 2002;13:S4. 4 BJOG 2001;108:320-24. 5 Ultrasound Obstet Gynecol 2001;18:511-14. 5 Int.Urogynecol.J. 1999;10:3-6. 6 Int.Urogynecol.J. 2001;12:104-06. 7 Neurourol.Urodyn. 2002;21:361-62.

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40 Robinson D1, Anders K1, Cardozo L1, Dixon A1 1. Kings College Hospital BLADDER WALL THICKNESS AND THE OVERACTIVE BLADDER: DO CONTRACTIONS COUNT? Aims of Study Measurement of bladder wall thickness (BWT) using transvaginal ultrasound has been shown to discriminate between women with detrusor overactivity and those with urodynamic stress incontinence (1). A mean bladder wall thickness of greater than 5mm has been found to be a sensitive screening method for diagnosing detrusor overactivity in symptomatic women without outflow obstruction (2) and is a useful adjunct to laboratory urodynamics (3). Women with detrusor overactivity have a thicker bladder wall than those with urodynamic stress incontinence suggesting that this change may be due to hypertrophy of the detrusor muscle secondary to repeated detrusor contractions against a closed urethral sphincter. The aim of this study was to test this hypothesis. Methods Women with lower urinary tract symptoms were recruited prospectively from a tertiary referral ambulatory urodynamic clinic as a consecutive series. All complained of irritative symptoms such as frequency and urgency with or without urge incontinence. Transvaginal ultrasound scans were performed in the supine position after asking the patient to empty the bladder. All measurements were made at maximum magnification, the bladder wall being measured perpendicular to the luminal surface in three places at the thickest part of: (1) the trigone, (2) the dome of the bladder, and (3) the anterior wall of the bladder. Mean BWT was then calculated as an average of the three measurements. Ambulatory urodynamics were performed by a second observer blinded to the results of the ultrasound bladder wall measurements. A single, solid-state 7F Galtec microtransducer with two pressure transducers was inserted into the bladder and a separate transducer was inserted into the rectum. The pressures were recorded on a solid-state ambulatory system (MPR2, Gaeltec). The test lasted four hours and the women were asked to drink 200 mls of fluid every 30 minutes and to keep a diary of events and symptoms. The results were analysed using a personal computer and detrusor instability was only diagnosed if a detrusor pressure rise was recorded in association with urgency or urge incontinence (4). In addition the number of detrusor contractions, mean amplitude, maximum amplitude and episodes of leakage were documented for each trace. Correlation was performed using the Pearson method. Results In total 128 women were recruited to the study. The ambulatory urodynamic diagnoses are shown below [Table 1]. Those women who were found to have urodynamic stress incontinence, voiding difficulties or a normal study were excluded, leaving 47 women with detrusor overactivity for analysis. Ambulatory Urodynamic Diagnosis No. % Normal 37 28.9 Urodynamic Stress Incontinence 43 33.6 Detrusor Overactivity 21 16.4 Voiding Difficulties 1 0.8 Mixed Incontinence 26 20.3 Table 1: Ambulatory Urodynamic Diagnosis Bladder wall thickness was correlated with number of detrusor contractions, mean amplitude, maximum amplitude and episodes of leakage and the results are shown below [Table 2]. Whilst there was a significant correlation with the mean detrusor contraction amplitude there was no correlation with number of contractions, maximum amplitude and episodes of leakage. Sub group analysis of correlations in women with an intact sphincter and those with sphincter incompetence were also performed [Table 3 and Table 4]. There was no correlation in those patients with detrusor overactivity and an intact sphincter although there was an association in those patients with mixed incontinence.

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Correlation Coefficent p value Number of Detrusor contractions r = 0.104 p = 0.486 Maximum Amplitude of contraction r = 0.007 p = 0.966 Mean Amplitude of contractions r = 1.000 p = 0.01 Episodes of leakage r = -0.155 p = 0.299 Table 2: Correlation of BWT with Ambulatory Findings in all Patients Correlation Coefficent p value Number of Detrusor contractions r = -0.256 p = 0.276 Maximum Amplitude of contraction r = 0.087 p = 0.716 Episodes of leakage r = 0.035 p = 0.883 Table 3: Correlation of BWT in Patients with Detrusor Overactivity Correlation Coefficent p value Number of Detrusor contractions r = 0.408 p = 0.039 Maximum Amplitude of contraction r = 0.136 p = 0.547 Mean Amplitude of contractions r = 1.000 p = 0.01 Episodes of leakage r = -0.223 p = 0.273 Table 4: Correlation of BWT in Patients with Mixed Incontinence Conclusions This is the first reported study to examine the hypothesis that increased BWT is caused by hypertrophy of the detrusor muscle secondary to repeated detrusor contractions against a closed urethral sphincter. Overall there would appear to be an association between mean amplitude of contractions and increasing hypertrophy of the bladder wall. However, sub-group analysis does not support the theory that an intact sphincter is a pre-requisite for this to occur. Whilst this is only a small study and is limited by the accuracy and reproducibility of ambulatory testing this may have implications when assessing the effect of anti-muscarinic therapy on bladder wall thickness. References 1. A novel technique for measuring bladder wall thickness in women using transvaginal ultrasound. Ultrasound Obstet Gynaecol 1994; 4: 220-223. 2. Ultrasound: a non-invasive screening test for detrusor instability. Br J Obstet Gynaecol 1996; 103: 904-908. 3. Can ultrasound replace ambulatory urodynamics when investigating women with irritative urinary symptoms? Br J Obstet Gynaecol 2002; 145-148. 4.Reducing artefacts in ambulatory urodynamics. Br J Urol. 1998; 81: 211-214.

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41 Canepa G1, Capponi G1, Campodonico F1, Maffezzini M1 1. E.O. Ospedali Galliera THE INFLUENCE OF TUR OR OPEN PROSTATECTOMY ON ULTRASOUND ESTIMATED BLADDER WEIGHT (UEBW): A PROSPECTIVE STUDY ON 26 PATIENTS. Aims of Study As reported in different papers by Kojima and Tubaro (1,2,3), a non invasive quantitative estimation of infravesical obstruction using ultrasonic measurement of bladder weight seems to be able to predict objectively and quantitatively the measurement of bladder hypertrophy. The objective of the study is to evaluate the effect of surgery or endoscopy on the detrusor hypertrophy in urinary obstructed patients using a non invasive method as ultrasound estimated bladder weight (UEBW).

Methods Between November 2002 and March 2003 a group of 26 patients already candidate for endoscopical or open prostatectomy were evaluated using ultrasound estimated bladder weight (UEBW), ultrasound bladder wall thickness (BWT), flowmetry and ultrasonic post-void residual (PVR). The estimated bladder weight was measured preoperatively, 4 weeks and 12 weeks postoperatively using transabdominal ultrasonography with a 7.5Mhz probe. A longitudinal scan was obtained on the midline of the lower abdomen above the distended bladder before an uroflowmetry. The thickness of the anterior bladder wall was measured at 3 points approximately 1 cm apart and the average value was recorded as BWT. Following ultrasonic measurement, infravesical volume was calculated by adding uroflowmetry voided volume and post-void residual urine volume estimated by ultrasound. Assuming the bladder as a sphere, UEBW was calculated from bladder wall thickness and infravesical volume as described by Kojima (1). The uroflow data reported were obtained by the same uroflowmetry for the bladder weight evaluation. All patients signed a preoperative informed consent also to permit a sample of the bladder wall and then underwent an already established operation: TUR or Open Prostatectomy. The ultrasound estimated bladder weight, BWT, uroflowmetry and PVR were performed 4 and 12 weeks postoperatively. It was also scheduled to complete the control at 24 weeks. Values are expressed as a mean plus or minus standard deviation. Statistical evaluation was performed comparing postoperatively data with baseline using Student’s t-test and <0.05 was defined as statistical significant. A statistical correlation between the results of two operations is calculated at 4 and 12 weeks controls. Results Twentysix men with a mean age of 70,88yrs (±8,01SD) were included. Fourteen (mean age 71,79yrs ± 6,97 SD) underwent open prostatectomy and 12 patients (mean age 69,83yrs ± 9.29 SD) transurethral resection. The two groups did not statistically differ for age. On Table 1 are reported all data obtained in the two groups of treatment at baseline and at each control. The comparison with baseline demonstrates that BWT decreases at each timing controls, with statistical significativity for TUR. The UEBW has a significant reduction after 4 weeks for TUR, and a numerical decrease after open surgery. Flowmetry demonstrates a no significant increase of the Qmax, instead of a contrastant evaluation of PVR after 12 weeks post TUR. No significant differencies are obtained comparing the results between the two groups at 4 and 12 weeks. No statistical correlation is obtained between BWT and the measurements of detrusor thickness specimens. Conclusions The results obtained seem to confirm the correlation between bladder hypertrophy and infravesical obstruction and the decrease of bladder wall thickness after surgical relief of obstruction: the uroflow improves as time passes, the postvoid residual volume decrease as ultrasonic estimated bladder wall thickness and bladder weight tend to decrease. In this study data obtained by ultrasound could be comparable with data reported in literature. The statistical analysis is influenced by the low number of patients at each control especially at 12 weeks, but a trend of the influence of TUR or open prostatectomy on the detrusor wall could be estimated. Ultrasound evaluation of the bladder hypertrophy would be, in a not far future, a non-invasive easy to use tool to support the diagnosis of the infravesical obstruction. All results are summarize in Table 1.

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Table 1

* p < 0.005 on Student’s t-test vs Baseline ** p < 0.005 vs Baseline ^ p = 0.005 vs Baseline ^^p = 0.005 vs Baseline ° p = 0.05 vs Baseline References 1. M. Kojima et al. Ultrasonic estimation of bladder weight as a measure of bladder hypertrophy in men with infravesical obstruction: a preliminary report. Urology 47:942-947,1996 2. M. Kojima et al. reversible change of bladder hypertrophy due to benign prostatic hyperplasia after surgical relief of obstruction J. of Urology 158, 89-93, July 1997 3. A. Tubaro et al. A prospective study of the safety and efficacy of suprapubic transvesical prostatectomy in patients with benign prostatic hyperplasia J. of Urology 166, 172-176 July 2001 42 Faltin D1, Boulvain M1, Floris L1, Weil A1, Irion O1 1. Dept Obstetrics and Gynaecology, University Hospitals of Geneva A RANDOMIZED, CONTROLLED TRIAL OF THE USE OF ENDOANAL ULTRASOUND AFTER DELIVERY TO DIAGNOSE ANAL SPHINCTER TEARS AND PREVENT FECAL INCONTINENCE Aims of Study Anal sphincter tears are frequently not diagnosed clinically after vaginal delivery and are associated with fecal incontinence. Whether diagnosis of these tears after delivery by ultrasound followed by repair prevents fecal incontinence is unknown. Methods We performed a randomized trial comparing clinical and ultrasound examination of the perineum after a first childbirth with clinical examination alone. The participants were women delivering vaginally their first child in which a superficial tear of the perineum not involving the anal sphincter was diagnosed by clinical examination. In the experimental group, ultrasound was performed immediately after delivery before suture of the perineum. When an anal sphincter tear was diagnosed, the perineum was surgically explored and the tear repaired. Women received a postal questionnaire three months and one-year after delivery. The main outcome was incontinence to flatus or liquid or solid stools graded with the Jorge Wexner fecal incontinence scale (range 0-20). A score above two (any symptom weekly or any two symptoms) was defined as fecal

TUR Baseline 4weeks 12weeks Patients 12 10 7 Age 69,83 ± 9,29ys - - BWT 0,37 ± 0.13cm 0,27 ± 0,07* 0.22 ± 0.07** UEBW 75,95± 23,71gr 58.36 ± 10.48* 66.91± 29.6 BWSpecimen 0.21 ± 0.06cm - - Q max 9.25 ± 3.89ml/sec 17.26 ± 6.77^ 21.96± 7.52^^ PVR 75.58ml 46.4 58.4 Prostatectomy Patients 14 8 4 Age 71,79 ± 6.97ys - - BWT 0.33 ± 0.12cm 0,24 ± 0.04 0,21± 0.05 UEBW 62,35 ± 19.07gr 44,86 ± 21.1 44,44± 18.9° BWSpecimen 0.45 ± 0.20cm - - Q max 3,62 ± 4.6ml/sec 15,23 ± 3,86 21,13 ± 4.1 PVR 92,2ml 17.48 9.41

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incontinence, a score above 4 was defined as severe incontinence. Proportions were compared with the chi-squared test and scores with the Mann-Whitney test adjusted for ties. Results We randomized 752 women after delivery. The base-line characteristics of the groups were similar. Among the 376 women assessed by ultrasound, 21 (5.6 percent) sphincter tears were diagnosed and 16 (4.3 percent) could be surgically repaired. Three months after delivery, 60/364 (16.5 percent) women reported fecal incontinence in the experimental group and 66/355 (18.6 percent) in the standard care group, risk difference -0.2 percentage point (95 percent confidence interval -7.7 to 3.5, P=0.46). Severe incontinence was reported by 12/364 (3.3 percent) women in the experimental group and 31/355 (8.7 percent) in the standard care group, risk difference -5.4 percentage point (95 percent confidence interval -8.9 to -2.0, P=0.0021). One year after delivery, 27/340 (7.9 percent) women reported fecal incontinence in the experimental group and 42/340 (12.4 percent) in the standard care group, risk difference -4.4 percentage point (95 percent confidence interval –8.9 to 0.1, P=0.06). Severe incontinence was reported by 12/364 (3.3 percent) women in the experimental group and 31/355 (8.7 percent) in the standard care group, risk difference -5.4 percentage point (95 percent confidence interval -8.9 to -2.0, P=0.0021). Among women affected by fecal incontinence, severity scores were lower in the experimental group three months (P=0.03) and one year post-partum (P=0.03). Conclusions Our study provide evidence that assessment of the anal sphincter after vaginal delivery is feasible, allows diagnosis and repair of sphincter tears otherwise overlooked. Taking these steps might reduce the severity and prevent fecal incontinence after childbirth. Fecal incontinence is a serious morbidity for the affected women and should be prevented as much as possible. The use of endoanal ultrasound should be considered after childbirth. 43 Van Hoeck K1, Bael A M1, Lax-Gross H2, Hirche H2, Vander Linden A 1, van Gool J D3 1. Pediatric Nephrology, University Hospital Antwerp, Belgium, 2. Institute for Medical Informatics, Essen University, Germany, 3. Urology, University Hospital Antwerp, Belgium VOIDED VOLUMES AND URINARY OUTPUT OF WATER AND SOLUTES, OVER A 72-HOUR PERIOD, IN 62 NORMAL SCHOOL-AGE CHILDREN Aims of Study In pediatrics, the maximum volume voided (‘maximum functional bladder capacity’) is used ubiquitously, usually related to age, for important clinical decisions. Values are obtained with the well-standardized tool of 3-day frequency/volume charts, but the factor(s) determining the volume of a given voiding have not been identified yet. This study was set up to compare the impact of biometric parameters, urine composition, and the time of voiding, on the voided volume in school-age children. Methods With informed consent of parents and teachers, 62 non-enuretic children from one primary school recorded the volume and the time of every voiding, and sampled every voiding, over a period of 72 hours. Ages of the 62 children (23 girls and 39 boys) ranged from 5.9 to 11.9 years. Informed consent, protocols and standardisation were based on a pilot study in 7 children. All collections were performed at home, with free intake of food and drinks, within the time span of one week. The volume voided first thing in the morning, after at least 6 hours of uninterrupted sleep, was labeled early morning volume (EMV). In all samples, osmolality was measured, as well as creatinine, calcium, and phosphate. The output of urine and osmoles was also expressed as ml and mOsm per kg bodyweight per hour, and the average hourly values were plotted on a 72-hour time scale [1].

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A multivariate stepwise logistic regression analysis was used to calculate the significance of the variables age, sex, height, bodyweight, time of day, urine osmolality, urine creatinine, urine calcium, and urine phosphate, with respect to the volume voided. Results Over a total of 183 twentyfour-hour periods, 1062 voided volumes were recorded, covering a very wide range, from 30 to 575 ml. The distribution of these volumes, expressed as ml per m2 body surface area, is skewed to the larger values. However, the EMV’s show a nearly normal distribution, suggesting they form a separate class. Univariate analysis shows that there are statistically significant coorrelations between the magnitude of the voided volume and urine osmolality, urine creatinine, and the biometric parameters height, weight, and body surface area. However, the magnitude of the voided volume is completely dependent of the time of the voiding: the largest volumes are by far obtained as EMV’s, right after 6 hours of uninterrupted sleep. The average hourly output of water and osmoles varies widely in rate at daytime, but the output of water drops consistently, every 24-hour period, at 21:00 hrs, to 0.8±0.2 ml/kg/hr. This rate is constant, until 07:30 hrs the next morning. Within these periods of constancy, the average hourly output of osmoles approaches and parallels the constant rate for the output of water, implying a continuously high osmolality. Conclusions The range of voided volumes obtained with accurately kept frequency/volume records is very wide. Although the magnitude of the volume correlates in a statistically significant way with urine osmolality and urine creatinine, as well as with the subject’s height and weight, the clinically relevant correlation for the magnitude of the volumes clearly is circadian time. This implies that night-time modulation of bladder control is different from daytime facilitation or inhibition. In the management of children with nocturnal enuresis, frequency/volume charts are less suited to find the maximum voided volume for a given child, as these children lack normal early morning voidings. The consistency of the circadian rhythm in the output of water and solutes warrants further research of this rhythm in children with monosymptomatic nocturnal enuresis. References 1. Van Mastrigt R, Eijskoot R. (1996). Analysis of voided urine volumes measured using a small electronic pocket balance. Scand J Urol Nephrol 28:257-263 44 Taylor C1, Bollard M2, Tang H3, Mouriquand P4, Foxall P1 1. Institute of Urology, London, 2. Biological chemitry, Imperial College, London, 3. Biolgical chemistry, Imperial College, London, 4. Hospital Debrousse, Lyon, France THE INVESTIGATION AND SUB-CLASSIFICATION OF RENAL TRACT IMMATURITY IN CHILDHOOD ENURESIS USING NOVEL METABONOMIC TECHNOLOGY.

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Aims of Study Metabonomics1,2 is an exciting and innovative technique, that determines systemic biochemical profiles and function regulation in whole organisms by analysing biofluids or tissues. The complex structure of the lower urinary tract, with co-ordination between several levels of the central nervous system required for functional control, means that enuresis has multiple aetiologies. Therefore, metabonomics, a non-specific and non-invasive analytical method is ideally suited to this complex problem. The aim of this study was to apply Nuclear Magnetic Resonance Spectroscopy (NMR) and Pattern Recognition (PR) technology (ie.metabonomics) to the differential diagnosis of childhood enuresis with the long-term goal being to avoid invasive urodynamics tests in these children. Methods Random urine samples were obtained from 53 children (age 1 month-16 years), with no structural or functional urinary tract pathology, which were designated a control group. Samples from 27 children (age 5-16 years) presenting with enuresis and no structural abnormalities or pharmacological treatment were also collected and designated the enuretic group. All children had a full clinical and laboratory history taken and their investigation results noted. 600 MHz 1H NMR measurements were obtained on all samples and the metabolic profiles produced analysed using the unsupervised PR methods of hierarchical cluster analysis (HCA) and principle components analysis (PCA)1,2. Results Analysis of the NMR data from the control group using HCA identified natural age-related groupings, namely 0-3 years, 4-7 years, 8-11 years and 12-16 years based on similarities in the urine biochemistry. PCA analysis of the same data showed an age related metabolic tragectory3 within the urine biochemistry, as evident in PC1 and PC2 (33% of the metabonome). PCA analysis of both the normal and enuretic children’s samples together revealed that 10 of the 27 enuretic children (37%) had urine that “clustered” with normal infants aged 0-3 years. This metabolic immaturity with respect to urine was also seen in two further enuretic children, aged 10 and 12 years respectively, who clustered in the 4-7 year area of the metabolic trajectory. Examination of the urodynamics performed on the 10 enuretic children showing metabolic immaturity showed some sub-classification. 5 of the children, aged 10-14 years, had features of hypertonicity and reduced bladder capacity on urodynamics in association with severe urinary metabolic immaturity. This group contained the children with refractory symptoms who were expected to have life-long continence problems. 4 children, age 5-8 years, had some unstable contractions but normal capacity and compliance, similar to those seen in normal infants on urodynamics, with mild metabolic immaturity. One child’s urodynamics were not available Conclusions Metabonomics is a powerful non-invasive and non-selective approach to identify metabolic changes with age and urinary tract function through urine analysis. Using metabonomics, we have demonstrated for the first time, that renal tract immaturity, as evident in urine biochemistry is present in enuretic children. We hypothesize that the younger enuretic children with mild immaturity on metabonomics and urodynamics will ‘catch up’ with the normal children over time and gain continence. In the long term, metabonomics could be used to sequentially plot the urine biochemistry over time to show this and reassure children and their families. The metabonomic identification of those urinary constituents that separate enuretic children with sever metabolic immaturity from normal children controls could ultimately lead to the development of new urinary diagnostic tests or form the foundation of new treatments. References 1. Brindle JT, Antti H, Holmes E, Tranter G, Nicholson JK, Bethell HW, Clarke S, Schofield PM, McKilligan E, Mosedale DE, Grainger DJ. Rapid and noninvasive diagnosis of the presence and severity of coronary heart disease using 1H-NMR-based metabonomics.Nat Med. 2002 Dec; 8(12):1439-1445 2. JK Nicholson, J Connelly, J Lindon and E Holmes. Metabonomics:a platform for studying drug toxicity and gene function Nat Reviews 2002 Feb; 1:153-162. 3. PJD Foxall, ME Bollard and PDE Mouriquand. The biochemical basis of bladder behaviour in children: a Novel approach to investigate age-related variations in urine biochemistry. BJU Int 2001,88:287.

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45 Buffa P1, De Gennaro M2, Battaglino F3, Beseghi U4, Di Lorenzo F5, Urso S6, Cama A1 1. Gaslini Institute - Genoa, 2. B.Gesu' Institute - Rome, 3. S.Bortolo Hospital - Vicenza, 4. General Hospital - Parma, 5. University of Bologna, 6. Coloplast - Bologna LONG TERM FOLLOW UP ON CONTINENCE AND RENAL FUNCTION IN 50 PATIENTS WITH CAUDAL REGRESSION SYNDROME. A MULTICENTER STUDY. Aims of Study Caudal Regression Syndrome (CRS) is a rare condition. It is a heterogeneous constellation of caudal anomalies (agenesis of the caudal spinal tract, anal imperforation, genital anomalies, dysplastic lower limbs, renal and pulmonary dysplasia, in variable association). It belongs to closed spinal dysraphism and may escape early diagnosis when anorectal malformation, cutaneous stigmata or severe lower limbs malformation are absent. Neurogenic involvement of micturition is very frequent and the risk of both upper urinary tract derangement and urinary incontinence is high. We developed a single database, with protected on-line access, to collect clinical data of patients with closed spinal dysraphism from 5 Italian paediatric centres, in order to collect as many cases as possible with a follow up long enough to assess the fate of upper urinary tract and the possibilities to treat urinary incontinence. This project started on January 2002. We present the results in 50 patients, focusing on those with severe impairment of continence and/or renal failure. Methods The inclusion criteria were the following:

1. Diagnosis of CRS (only sacral or lumbo-sacral defects were considered essential). 2. Imaging about spinal defect and spinal cord available. 3. Available description of urodynamic observations associated with characteristic symptoms and

signs. 4. Serum creatinine, renal sonography and/or scanning available. 5. Follow up longer than 10 years.

The database, powered by a professional agency, is accessible on-line from the five Italian centres and protected by passwords. Patient’s family name is shown only cryptic, but the system is able to recognise if a new patient has been previously inserted by another centre, allowing to append new clinical observations without duplicating the record (one patient – one record). Each operator can modify or implement only the data belonging to his own patients, but is able to know clinical features of all the patients. The entire database can be analysed through a number of queries. Results Fifty patients, 27 females and 23 males, were considered eligible. Mean age was 13.3 years (range: 11.2 to 35.9). An anorectal malformation was found in 14 patients, 2 of which had a cloaca. Unilateral renal agenesis was found in 8, while 1 patient underwent nephrectomy for multicystic kidney. Seven patients (14%) have normally innervated bladder and are continent, only 2 of which complaining of episodes of nocturnal enuresis. Of the remaining 43 patients with neurogenic bladder, 21 (48.9%) are dry between voiding obtained either by intermittent self-catheterisation or by bladder expression, 5 (11.6%) are usually dry up to 2 ½ hours (with dribbling linked mainly to their physical activity, amount of fluid uptake and emotional status) and 14 patients (32.5%) are moderately to severely incontinent; the remaining 3 (6.9%) had permanent urinary diversion due to complex pelvic malformations in which urinary and digestive tract could not be reconstructed in infancy. One of these last has recently undergone bladder reconstruction by ileocecal reservoir with Mitrofanoff continent conduit (appendix). Upper urinary tract is mildly dilated in 12 (24%) and moderately dilated or scarred in 6. Severe derangement was found in only one case and led to transplantation. Vesico-renal reflux was found in 24 renal units of 16 patients, all but one successfully treated. Overall renal function is slightly impaired in 4 (serum creatinine between 1.2 and 1.4 mg/dL, all young adults), moderately impaired in one (1.9 mg/dL, 25 years old) while a patient who underwent multiple

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surgical procedures including temporary diversion, developed an end stage renal failure and underwent successful renal grafting. One patient recently died, due to unrelated cause. Conclusions Matching urological data and imaging of all patients with impaired renal function, we could observe that bony defect exceeded 3 sacral bodies except in a patient with complicated multi stage surgical treatment and in another one who came too late to intermittent catheterisation practice. Extensive bony defect is also present in all the patients with dilatation of upper urinary tract except in one with complex pelvic malformation (cloaca). The great majority of severely affected patients shows club shaped cord( high lying and without the normal taper), with double bundle shape of the cauda equina and no lipomatous tissue or tethering Renal agenesis has an exceedingly high rate (16%) and vesico-renal reflux affects one third of the patients. Only a minority of patients escape neurological involvement of micturition (14%) and barely half of those with neurogenic bladder do not need diapers unless undergoing bladder neck surgery. RReeffeerreenncceess Boemers T.M.L., de Jong T.V.P.M., van Gool J.D., Bax K.M.A. : Urologic problems in anorectal malformations. Part 2: functional urologic sequelae. J Pediatr Surg 31: 634-637, 1996 Duhamel B.: From The Mermaid To Anal Imperforation: The Syndrome Of Caudal Regression. Arch Dis Child 36: 152-155, 1961 Pang D.: Sacral Agenesis And Spinal Cord Malformations Neurosurgery 7: 118-126, 1980 Renshaw T.S.: Sacral agenesis. A classification and review of twenty-three cases. J Bone Joint Surg 60A: 373-383, 1978

46 Bower W1, Yeung C1 1. The Chinese University of Hong Kong PERCEPTION OF THE NEED FOR A PAEDIATRIC BLADDER DYSFUNCTION QUALITY OF LIFE MEASURE. Aims of Study Until recently 'quality of life' in children has been a paradigm associated more with life-threatening diseases than with organic or functional disorders (1). Although the psychological impact of incontinence has been frequently measured in children (2), a more general and holistic assessment of bladder dysfunction from the child's perspective has not been routinely obtained. Given that quality of life measures are a potent indicator of treatment outcome in adult continence patients, and that data can be used to assist in clinical decision-making (3) and to justify resource allocation (4), the use of such tools in children warrants consideration. The aim of this study was to evaluate the perception among expert clinicians in the field of paediatric bladder dysfunction of the need for a cross-cultural tool capable of measuring the breadth of quality of life issues in affected children. A further aim was to identify international centers willing to conduct structured interviews or focus groups with patients and to collect data from children across a number of cultures that informs an understanding of the impact of bladder dysfunction on their individual wellbeing. Methods 120 expert clinicians within the field of childhood bladder dysfunction were contacted by email and asked to complete a questionnaire seeking an opinion on six aspects of the measurement of quality of life in children. This is a similar methodology to that used successfully in the first phase of the conception of the European Kidscreen, a generic health-related quality of life questionnaire (5). Clinicians were also questioned about their willingness to conduct a small number of structured patient interviews / a focus group with the aim of

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identifying the relative importance to children of bladder function, dysfunction and treatment. An interview package for administration to affected children was then prepared and sent to study collaborators. Results None of the clinicians were aware of a specific bladder dysfunction quality of life measure that could be used in children, and 76% of responders did not routinely attempt to measure the psychosocial effects of this disorder. The most commonly used tool was the Child Behavioural Checklist. An overwhelming 94% of clinicians perceived a need to measure quality of life aspects in children with bladder dysfunction and cited two equally important benefits: the ability to evaluate treatment outcome / treatment quality assurance, and the facilitation of research. When presented with 11 possible domains of measurement that are evaluated in generic paediatric tools, clinicians prioritised measures of: social relations with peers (82%), self-esteem (79%), family and home function (66%), body image (64%), and independence and mental health (58% and 55% respectively). There was minimal support for the evaluation of cognitive competence, energy levels or aspirations for the future. Despite the fact that proxy completion of impact questionnaires may not adequately reflect the child's perception of wellbeing, 76% of clinicians perceived value in having a parallel tool completed by a parent or caregiver. Opinion was equally split between the need for a stand alone bladder dysfunction quality of life measure and a specific module that could be appended to an existing generic paediatric quality of life measure. Responders represented 13 countries and in 97% of cases were willing to collaborate with structured patient interviews. These sessions are currently being conducted and the data collected will be available within a few months. Conclusions There is a perceived clinical need for a robust disease-specific measure of psychosocial aspects of quality of life in children with bladder dysfunction that can be used as an outcome measure of treatment efficacy and an adjunct to research initiatives. Once the child-reported impact of bladder dysfunction on individual wellbeing is understood, a paediatric bladder dysfunction quality of life tool will be tailored and tested for content and construct validity, sensitivity to change and reliability. References 1) Gerharz EW, Eiser C, Woodhouse CRJ. Current approaches to assessing the quality of life in children and adolescents. BJU Int. 91:150-154, 2003 2) Theunis M, van Hoecke E, Paesbrugge S et al. Self-image and performance in children with nocturnal enuresis. Europ Urol 41:660-667, 2002 3) Osoba D. Quality of life measures as treatment outcome variables. Lecture at The Chinese University of Hong Kong, Jan 2003 4) Wallander JL, Schmidt M, Koot HM. Quality of life measurement in children and adolescents: issues, instruments and applications. J Clin Psych 57(4):571-585, 2001 5) Herdman M, Rajmil L, Ravens-Sieberer U et al. Expert consensus in the development of a European health-related quality of life measure for children and adolescents: a Delphi study. Acta Paed 91;1385-1390, 2002 47 Kajiwara M1, Inoue K1, Usui A2, Usui T1 1. Department of Urology, Graduate School of Biomedical Sciences, Hiroshima, Japan, 2. Prefectural Hiroshima rehabilitation hospital, Japan TIMED VOIDING THERAPY FOR CHILDREN WITH DAYTIME URINARY INCONTINENCE ATTRIBUTABLE TO OVERACTIVE BLADDER Aims of Study The aetiology of daytime urinary incontinence (DUI) in children is assumed to be multifactorial, but mainly attributable to overactive bladder (OAB). The aim of this study is to examine the efficacy of timed voiding therapy for children with DUI attributable to OAB.

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Methods Children with DUI due to OAB treated with timed voiding therapy between 1998 and 2001 were included in this study. To investigate the urological and neurological conditions in these children, all of them underwent voiding cystourethrography and pressure flow study (PFS). The inclusion criteria were; children over 6 years old, without neurological abnormalities and without urethral obstruction such as posterior urethral valves and urethral strictures. First, the mechanism of normal micturition and urge urinary incontinence was explained to the children and their parents. To obtain stabilization and relaxation of the lower urinary tract and pelvic-floor muscles, they were instructed (1) to go to the toilet frequently, within regular intervals before feeling the urge, (2) not to postpone their desire to void with a characteristic holding maneuver and (3) to avoid constipation leading to anal and simultaneous urethral sphincter contraction. The efficacy of this behavioral modification was assessed by a questionnaire about micturition symptoms and by frequency/volume charts, according to the definition of the clinical outcome conformed to the International Children’s Continence Society. To examine the differences in response to the treatment, we compared the PFS findings for responders (Complete cure and Improvement) with those for non-responders, before and after treatment. The data were analysed statistically using non-parametric tests (Mann-Whitney U test and the chi-squared test). Results Twenty-eight children (12 boys and 16 girls aged between 6 and 11 years, mean age 8.4 years) were included. The mean follow-up time was 17.3 months (6–29 months). Clinical outcome; DUI was cured completely in 12 children (42.9%) and improved in 11 (39.3%). No adverse reaction was detected. PFS findings; Before treatment, there were no apparent differences in the mean maximum flow rate (Qmax), mean detrusor pressure at maximum flow rate (Pdet Qmax) and mean maximum detrusor pressure during the filling phase (Max Pdet) between the two groups. However, in non-responders before treatment, the mean voided volume (VV) was significantly lower and the incidence of involuntary detrusor contraction (IDC) during the filling phase was higher, compared with those in responders. In both groups after treatment, the mean Qmax and mean VV were not changed compared with those before treatment. In responders, the mean Pdet Qmax and mean Max Pdet were decreased significantly, whereas they were not reduced significantly in non-responders after treatment. In responders, the incidence of IDC, 82.6% (19/23) before treatment, was reduced to 39.1% (9/23) after treatment, while all of the non-responders had IDC before and after treatment (Table). Conclusions Timed voiding therapy was effective in 78.6% of children with DUI. Children with a small functional bladder capacity responded poorly. Timed voiding therapy was helpful for avoiding the IDC and for decreasing the detrusor pressure during the filling and voiding phases, thus stabilizing and relaxing the lower urinary tract and pelvic-floor muscles. Timed voiding therapy might be a simple, safe and effective strategy for children with DUI attributable to OAB. Table Comparison of pressure flow study findings before and after treatment in responders and non-responders *p<0.05

Responders Non-Responders

Before After Before After VV (ml) 198±106 194± 90 * 101±34 118±71 Pdet Qmax mean±SD(cmH2O) 69.0±46.3 43.5±18.7 * 61.8±19.0 40.4± 9.5 Max Pdet mean±SD(cmH2O) 97.5±50.2 54.6±24.3 * 93.4±29.7 50.5± 6.7

IDC N (%)

19/23 (82.6%)

9/23 (39.1%)

5/ 5 (100 %)

5/ 5 (100 %)

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48 Staehler M1, Sauter T1, Miller K1 1. Dept. of Urology, Free University of Berlin BOTULINUM TOXIN A INJECTION IN THE M. DETRUSOR VESICAE REPLACES SURGERY IN CHILDREN WITH MYELOMENINGOCELE Aims of Study Botulinum Toxin A (BTxA) is used widespread in neurology and plastic surgery with very good results. Some groups used BTxA for the treatment of detrusor hyperreflexia in spinal cord injury. We propose BTxA in children with incomplete spinal lesion and detrusor hyperreflexia refractory to anticholinergic medication, where bladder augmentation is the only alternative. Methods We enrolled 31 children with a mean age of 9.5 a (2.3-17.3) from 10/1999 to 09/2002. All patients had intolerable detrusor pressure over 40 cmH2O due to myelomeningocele (n=30) or spinal meningeoma (n=1), although they were on combined intravesical and oral anticholinergics. All patients used clean intermittent catheterization (CIC). BTxA injection was carried out under general anesthesia in a latex-free environment using a 21G Chiba needle to do the injections cystoscopically. We used 5-10 IE BTxA (Botox®, Merz & Co., GmbH & Co, Dysport®, Ipsen Pharma, Germany) ad 0,1ml NaCl per injection site at a total of 150 – 300 IU. The injections were distributed all over the bladder excluding the trigone. Urodynamic reevaluation was performed in a 6-8 weeks interval. Results With a median follow-up of 14.5 months we determined that BTxA needs 6 weeks before relevant urodynamic changes can be seen. Intravesical Pressure could be reduced for a mean of 9.26 months (6 mo. – 1.25 years) with repeated injections seeming to prolong the action time of the toxin. In 4 cases BTxA toxin had to be reinjected within 3 months. In 5 cases anticholinergic medication could be stopped, in 5 more cases anticholinergic treatment could be reduced. We had no complications intra- and postoperatively, and no side effects were seen. In 30 children surgery was avoided until now. Only one patient did not respond to the treatment and bladder augmentation had to be performed at last. All urodynamic parameters improved significantly (*p<0.005) as seen in the table.

Pre Botox After Botox

Max.Detrusor Pressure cmH2O 72 ± 27 36 ± 9*

Leak-Point-Pressure cmH2O 60 ± 29 46 ± 28*

Compliance ml/cmH2O 7 ± 5 12 ± 8*

Bladder Volume ml 272 ± 133 307 ± 139

Conclusions Long term efficacy of botulinum toxin injection was demonstrated with significantly improved urodynamic situation. The minimally invasive procedure had no side effects. In some case we confirmed BTxA as an alternative to anticholinergic medication. Thus we proofed that BTxA injection in the M. detrusor vesicae is a safe and efficient alternative to surgery.

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49 Herschorn S1, Corcos J2, Gajewski J3, Schulz J4, Ciu E5 1. University of Toronto, 2. McGill University, 3. Dalhousie University, 4. University of Alberta, 5. Janssen-Ortho CANADIAN URINARY BLADDER SURVEY: POPULATION-BASED STUDY OF SYMPTOMS AND INCONTINENCE Aims of Study There have been very few epidemiologic studies to ascertain the prevalence of urinary incontinence in Canada and the reported rate has been lower than that seen in studies from other countries (1). Furthermore there has never been a survey that measures the impact severity and rate of treatment seeking behaviour in individuals affected with the condition. A cross Canada telephone survey was therefore undertaken to ascertain the prevalence of incontinence and related lower tract symptoms and treatment in adult men and women. Methods A standardized survey was created to elicit information about prevalence, duration, severity of incontinence and other urinary symptoms as well as treatment sought and obtained from healthcare providers. The population studied was non-institutionalized and non-medical-practiced based. Canadian Ipsos-Reid, a research company with a national network of over 600 Computer-Assisted Telephone Interviewing (CATI) stations, was commissioned to conduct the surveys. A 2-part urinary tract questionnaire was administered to 2 cohorts of 1000 adults during 2 separate weeks in October 2002. Each sample was stratified to reflect the population with regard to gender and distribution according to the 2001 national census. Data analysis was done with standard statistical software including SPSS and SAS. The major form of analysis on the data was cross-tabulation. Results Data were collected and analyzed from 2000 respondents. The answers to the common first questions in both questionnaires, regarding prevalence of symptoms, were similar as were the results in the 6 geographic regions across the country. While only 8% of all respondents initially acknowledged having a bladder problem (Males 5%; Females 12%), 52% answered ‘yes’ to having one or more bladder symptoms. With these respondents the commonest symptoms were nocturia (38%), urgency (16%), frequency (14%), stress incontinence (13%), and urge incontinence (7%). Mean duration of bladder symptoms was 9.1 years. Table 1 shows the breakdown by gender and age. Table 1: Prevalence of urinary symptoms by gender and age Gender Age (y) Number of respondents Any symptom

Male 958 45%

Female 1042 58%

18-40 836 41%

41-64 900 59%

>=65 236 67%

Nocturia 34% 43% 29% 43% 58% Urgency 17% 16% 13% 18% 22% Frequency 12% 16% 12% 15% 20% Stress Incontinence 3% 23% 7% 18% 18% Urge Incontinence 4% 10% 3% 9% 16% The overall prevalence of any degree of urinary incontinence symptoms was 21.8% with one quarter of these respondents having a moderate to large degree of leakage and moderate to severe interference with everyday life. Table 2 shows the percentage of males and females with any degree of incontinence stratified by age. Table 2: Prevalence of incontinence by gender and age

Age (y) 18-40 41-64 >=65

Males 10% 16% 30% Females 16% 33% 55%

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Overall only 26% of those with any bladder problem have seen a doctor or other health care professional for it and of those 67% received treatment including exercises, medication, and/or surgery. Conclusions This is the first survey of this type done in Canada to ascertain prevalence in the general population. Urinary incontinence had a higher prevalence in this study than the 7% previously reported (1) and is similar to that in other national studies (2). The prevalence similarly increases in women and older age groups. Despite the prevalence many of those with troublesome symptoms have not sought nor have received treatment for the problem. This suggests the need for more effective strategies to provide continence care. References 1. Urinary Incontinence. In: Promoting a Collaborative Approach to Continence Care in Canada, Canadian Continence Foundation, July 2001, pp 1-9. 2. Hunskaar S et al. Int Urogynecol J, 2000; 11:302-309. 50 Lin A T1, Lin A D1, Wang P S 2, Chen K K1 1. Taipei Veterans General Hospital, 2. National Yang Ming University INCREASED NOCTURNAL URINE VOLUME IS ASSOCIATED WITH A GONADOTROPIN-INDEPENDENT REDUCTION OF NIGHTTIME SERUM TESTOSTERONE LEVEL IN MALE NOCTURIA PATIENTS Aims of Study Nocturia is common in the aging male. One factor is an increased nocturnal urine volume. However, the reasons for the increased urine amount in the night remain unclear. Sex steroid hormone has been found to play a role in regulation of water/solute excretion. It would be valuable to know that is there any correlation between androgen status and nocturnal urine production in men with nocturia. Methods The study includes 22 male patients (mean age 75.3 years old) with nocturia (�2 micturition per night). All record a voiding diary and collect urine for 3 successive days. The urine voided immediately following wakeup in the morning is included in the nighttime urine sample. Samples of urine collected separately at daytime and nighttime are sent for assay of sodium and calcium. Serum samples at 7am and midnight are obtained and sent for determination of testosterone and luteinizing hormone (LH) with radioimmunoassay. Sodium and calcium excretion are calculated and normalized as meq/Kg/hour and mg/Kg/hour respectively. We correlate the ratio of nocturnal urine volume over 24-hour urine volume with various parameters using Pearson’s correlation test. Results Patients void 4.6+2.1(range 2.0-9.5) times per night. The ratio of nocturnal urine volume ranges from 0.22 to 0.69, with a mean of 0.43. There is a significant positive correlation between nighttime sodium excretion and the ratio of nocturnal urine volume(R=0.438, P<0.05). However, excretion of calcium, either in daytime or in nighttime, does not have significant correlation with the ratio of nocturnal urine volume. Interestingly, patients with higher ratio of nocturnal urine volume have lower serum testosterone level in the midnight(R= -0.562, P=0.008)(figure). But in the morning, serum testosterone level does not have significant correlation with the ratio of nocturnal urine volume. Serum LH level, either at 7am or at midnight, shows no significant correlation with the ratio of nocturnal urine volume.

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Conclusions This study shows that the increased nocturnal urine excretion is mainly due to an increased nighttime sodium excretion. We also demonstrate that more nocturnal urine volume is associated with a gonadotropin-independent reduction of serum testosterone level in the nighttime. Future studies are required to determine the significance of and causes for the decreased nighttime serum androgen level in male patients with nocturnal polyuria. 51 Kim J C1, Lim P B1, Seo S I1, Park Y H 1, Hwang T1 1. Dept. of Urology, Kangnam St. Mary's Hospital, College of Medicine, The Catholic University of Korea CHANGES OF URINARY NERVE GROWTH FACTOR AND PROSTAGLANDINS IN MALE PATIENTS WITH LOWER URINARY TRACT SYMPTOM Aims of Study Lower urinary tract symptom (LUTS) are highly prevalent in elderly men. Bladder outlet (BOO) is one of the principal causes of LUTS; in addition to BOO, detrusor factors such as detrusor overactivity and underactivity can contribute to the development of LUTS. Most of patients with LUTS have irritative or storage symptom such as frequency and urgency. Some of these effects may be due to alterations in the intrinsic peoperties of the bladder smooth muscle and others may be related to changes in the neural control of the bladder. Nerve growth factor (NGF) is a secretory protein which plays a critical role in the development of the peripheral nervous system. Increased expression of the NGF in the urinary bladder may contribute to irritative symptoms in patients with LUTS. Prostaglandin (PG) affect the micturition reflex and the bladder is a site of PG synthesis. Therefore, NGF and PGs can be related to irritative or storage symptom in patients with LUTS. This study was performed to investigate the changes in urinary NGF and PGs in male patients with LUTS. Methods The study groups included 75 male patients with LUTS (mean age 62.5) and 20 patients without LUTS (mean age 56.8) as reference control. The evaluation included history taking, urinalysis, international prostatic symptom score (IPSS), and urodynamic study. Voided urine was collected in all patients. The urinary NGF, PGE2, PGF2α and PGI2 concentration was analysed by using an enzyme linked immunosorbent assay and these results were compared with the control group. Also, urinary NGF and PGs concentration was correlated with IPSS score (obstructive and irritative) and urodynamic parameters (first voiding sense, maximal bladder capacity, presence of detrusor overactivity and underactivity, and presence of BOO) in LUTS patients.

Figure. Correlation betwen midnight testosterone level and nocturnal urine production

Ratio of nocturnal urine volume0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8

Test

oste

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at 2

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(pm

ole/

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0

1000

2000

3000

4000

5000R= -0.562, P=0.008

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Results From the analysis of the IPSS, the obstructive and irritative symptom scores were increased in LUTS patients. The urodynamic study in LUTS patients showed that more than half of the patients had detrusor overactivity (51%) and BOO (53%). The incidence of underactivity was noted in 7 patients (9%) in LUTS patients. The urinary concentration of NGF and PGE2 were significantly increased in patients with LUTS compared with control (p<0.05). However, the concentration of PGF2α and PGI2 were not significantly different between LUTS and control patients. In LUTS patients, the concentration of PGE2 was decreased in patients with underactivity compared with patients without underactivity (p<0.05). Furthermore, the concentration PGE2 was negative correlated with maximal bladder capacity in LUTS patients (p<0.05). The urinary NGF, PGF2α, and PGI2 were not correlated with IPSS score and urodynamic parameters in LUTS patients. Conclusions This study has demonstrated that the NGF and PGE2 have important role in male patients with LUTS, and PGE2 can change according to detrusor function. Also, these changes can be confirmed with analysis of urine. Therefore, these results may be used as urinary markers to evlauate the detrusor dysfunction in LUTS patients. 52 Takahashi S1, Takeuchi T1, Tomita K1, Homma Y1, Kitamura T1 1. Dept. of Urology, Tokyo University THE CLINICAL EFFICACY OF NAFTOPIDIL ON OVERACTIVE BLADDER IN PATIENTS WITH BENIGN PROSTATIC HYPERPLASIA Aims of Study Naftopidil ((±)-1-[4-(2-methoxyphenyl)piperazinyl]-3(1-naphthyloxy)propan-2-ol) is an alpha-1 adrenoceptor blocker which acts more selectively on the lower urinary tract than on the blood vessels. Naftopidil shows high affinity for alpha-1A and 1D adrenoceptor subtypes, which are both expressed in human prostate and bladder. Significantly, the predominant subtype mRNAs in prostate and bladder have been reported to be alpha-1A and 1D, respectively (Nasu 1996, and Malloy 1998). Therefore, it can be assumed that naftopidil improves irritative bladder symptoms as well as obstructive symptoms derived from benign prostatic hyperplasia (BPH). In the present study, we evaluated the efficacy of naftopidil on overactive bladder (OAB) in patients with BPH, using Frequency/Volume charts (FVC). Methods The study was conducted at 11 centers. A total of 66 patients with BPH (54 to 91 years, mean age 68.6 years) were studied. The inclusion criteria were; 1) a score of eight or more points on the International Prostate Symptom Score (I-PSS), 2) three or more points in any of the scores for 3 items (frequency, nocturia, and urgency) of I-PSS that assess irritative symptoms. The ethics committee of the hospital approved this study and informed consent was obtained from each patient. The patients received 50-75 mg/day of naftopidil for six weeks. All the patients were examined for FVC (number of voids during the daytime and nighttime, mean urine volume/void, and mean urine volume/day) before and after the 6-week administration of naftopidil. I-PSS, QOL score, and Uroflowmetry were also evaluated before and after the administration. Results After the administration of naftopidil for 6 weeks, I-PSS total scores decreased significantly from 18.7 to 11.1 points (p<0.001). Both irritative and obstructive symptom scores showed significant improvements (both p<0.001). The score for urgency, which indicates the existence of OAB significantly decreased from 3.0 to 1.7 (p<0.001). QOL score also improved from 4.6 to 3.2 (p< 0.001). In objective findings , the maximum flow rate increased from 10.2 to 12.4 ml/s (p< 0.05).

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Number of voids during the daytime and nighttime decreased from 9.5 to 8.5 (p<0.01) and from 2.6 to 2.0 (p<0.001), respectively. Mean urine volume/void increased from 165.3 to 182.6ml (p<0.001). Number of voids during the nighttime decreased from 3.3 to 2.5 in 47 patients who suffered from nocturia (2 times or more), (p<0.001). Nocturnal polyuria may also cause nocturia. Therefore, we defined the patient whose nocturnal polyuria index (nocturnal urine volume/ 24-hour urine volume) was greater than 0.35 as a case with nocturnal polyuria. We found that 19 patients met this criterion. Interestingly, these patients showed an improvement in their nocturia that was comparable to the cases without nocturnal polyuria (p<0.01). Conclusions These results suggest that naftopidil, an alpha-1A and 1D adrenoceptor blocker improves not only obstructive symptoms but also OAB symptoms. Naftopidil may be effective for nocturia in patients with BPH, regardless of the existence of nocturnal polyuria. References 1. Nasu, K., Moriyama, N., Kawabe, K., Tsujimoto G., Murai, M., Tanaka, T., Yano, J.: Quantification and

distribution of alpha 1-adrenoceptor subtype mRNAs in human prostate: comparison of benign hypertrophied tissue and non-hypertrophied tissue. Br J Pharmacol 1996, 119: 797-803

2. Malloy, B.J., Price, D.T., Price, R.R., Bienstock, A.M., Dole, M.K., Funk, B.L., Rudner, X.L., Richardson, C.D., Donatucci, C.F., Schwinn, D.A.: Alpha1-adrenergic receptor subtypes in human detrusor. J Urol 1998, 160: 937-43

53 Verhamme K1, Dieleman J1, Bleumink G 2, Bosch R 3, Stricker B2, Sturkenboom M1 1. Erasmus MC, Department of Epidemiology and Biostatistics, Department of Medical Informatics, 2. Erasmus MC Rotterdam, Department of Epidemiology and Biostatistics, 3. Erasmus MC Rotterdam, Department of Urology TREATMENT STRATEGIES, PATTERNS OF DRUG USE AND TREATMENT DISCONTINUATION IN MEN WITH LUTS SUGGESTIVE OF BENIGN PROSTATIC HYPERPLASIA – THE TRIUMPH PROJECT (1) Aims of Study Benign prostatic hyperplasia (BPH) is common in elderly men. Patients with BPH can be free of any symptoms. They often suffer however from lower urinary tract symptoms (LUTS) related to difficulties in voiding or storage. Based on the severity of the symptoms patients either receive no treatment, pharmacological treatment or prostate surgery. We aimed to describe the treatment strategies, the adherence to pharmacological treatment and to investigate whether the type of main LUTS/BPH complaints predicts early treatment discontinuation. Methods Within the GP research database (IPCI) in the Netherlands we identified all males aged 45 years or older with at least 6 months of valid database history and newly diagnosed with LUTS/BPH during 1995-2000. Within this cohort we searched for all cases of prostate surgery and calculated the incidence rate for prostate surgery. Pharmacological treatment was assessed between the date of LUTS/BPH diagnosis and the end of study period. Patterns of drug use were described in terms of switching, adherence and early treatment discontinuation. Patients were considered to have discontinued treatment early if they received only one episode of treatment taking up less than 20% of the follow-up time. Adherence to therapy was defined as the duration of an episode divided by the time-interval between the start of that episode and the start of the next. Logistic regression analysis was used to study the association between the type of main urinary complaints at the start of pharmacological treatment and the risk of early treatment discontinuation. In accordance with the ICS standardization report on the terminology of lower urinary tract function (2), urinary complaints were classified in 3 categories: storage symptoms, voiding symptoms and post micturition symptoms. If the reason for starting pharmacological treatment was only indicated as “BPH” or “prostatism” and no specific complaints were listed, the patients were classified as having “prostatism

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symptoms”. Adjustment was made for possible riskfactors such as age, dosing regimen, chronic disease score (CDS) and PSA measurement. The CDS is based on the use of drugs as a proxy for long-term diseases, allowing for the construction of an overall index of chronic disease status (3-4). Results Of the 2214 men with incident LUTS/BPH, 1075 (49%) received pharmacological treatment and 238 (11%) underwent prostate surgery. The overall incidence of prostate surgery was 62/1000 men-years (95%CI: 54.4-70.2). The incidence increased with age from a low incidence of 20.7/1000 men-years (95%CI:4.1-66.3) at the age of 45-49 years to a high incidence of 106/1000 men-years (95%CI:81.5-137) at the age of 75-79 years. The majority of the patients received their first pharmacological treatment within 1 year after diagnosis. The average adherence to α-blockers was 67% (95%CI:66-68%), to 5α-reductase inhibitors 73% (95%CI:69-77%) and to combination therapy 71% (95%CI:49-93%). Switching occurred in 12% of the patients. Of the treated population, 280 patients (26%) discontinued treatment early mainly due to symptom improvement (19%), adverse events (28%) and/or persistence of complaints (24%). The probability of early discontinuation was higher in patients with complaints of mainly voiding symptoms (ORadj 3.39 (95%CI:1.90-6.05)), mainly post-micturition symptoms (ORadj 2.41 (95%CI:1.17-4.96)) or mainly storage symptoms (ORadj 1.83 (95%CI:1.14-2.92) as compared to patients complaining of the combination of storage, voiding and/or post micturition symptoms. Normal PSA measurement as compared to no PSA measurement being done (ORadj 1.48;95%CI:1.07-2.04) was associated with early discontinuation. Older age(> 60 years) and a higher chronic disease score were associated with a lower risk for early treatment discontinuation. In the univariate analysis, a once daily dosing regimen as opposed to multiple dosing a day was associated with a reduced risk for early treatment discontinuation (OR 0.72;95%CI:0.53-0.98) but this association was no longer statistically significant when adjusting for all riskfactors (ORadj 0.75 (95%CI:0.55-1.04)). Conclusions Forty-nine% of the LUTS/BPH are pharmacologically treated. Adherence differed slightly between treatments. The risk for early treatment discontinuation was highest in patients younger than 60 years without co-morbidity, with normal PSA values as opposed to having had not PSA measurement at all and with voiding symptoms as main complaint. Patients complaining of the combination of storage, voiding and post micturition symptoms have more severe or more bothersome LUTS/BPH what may contribute to the lower rate of early treatment discontinuation. Men complaining of LUTS/BPH who turn out to have a normal serum PSA value might find reassurance in this result and be less motivated to continue treatment. Further studies are needed to test this hypothesis. 1.Chapple C. Lower urinary tract symptoms suggestive of benign prostatic obstruction – Triumph: design and implementation. Eur Urol 2001;39 Suppl 3:31-6 2. Abrams P, Cardozo L, Fall M, Griffiths D, Rosier P, Ulmsten U, van Kerrebroeck P, Victor A. Wein A. The standardization of Terminology of Lower Urinary Tract Function: Report from the standardization sub-committee of the International Continence Society. Neurourology and urodynamics 2002; 21:167-178 3. Von Korff M, Wagner EH, Saunders K. A chronic disease score from automated pharmacy data. J Clin Epidemiol. 1992;45:197-203 4. Johnson RE, Hornbrook MC, Nichols GA. Replicating the chronic disease score (CDS) from automated pharmacy data. J Clin Epidemiol 1994;47:1191-1199

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54 Williams K1, Assassa R P1, Cooper N1, Turner D1, Shaw C1, Abrams K1, Mayne C1, McGrother C1 1. University of Leicester RANDOMISED CONTROLLED TRIAL OF THE CLINICAL AND COST EFFECTIVENESS OF EXISTING CONTINENCE SERVICES COMPARED WITH A NEW NURSE-LED SERVICE. Aims of Study Current care provision for urinary symptoms is fragmented and inconsistent with consistent care pathways rarely in place. The aim of this study was to evaluate the impact of a new Continence Nurse Practitioner (CNP) led service compared to existing primary/secondary care provision for individuals with urinary incontinence and storage symptoms. Methods 3746 community dwelling men and women aged 40 years and over were recruited into a randomised controlled trial. Individuals were randomised either to a new nurse-led service or existing care in the ratio 4:1; intervention n=2958 and control n=788. The intervention comprised a CNP led service, provided by nurses who had undergone extensive training (1), delivering standardised evidence based interventions for storage symptoms (2). The primary outcome measures were validated symptom questions on incontinence, frequency, urgency and nocturia (3), with secondary outcome measures comprising a validated impact scale (4) on activities and feelings, cost-effectiveness and satisfaction. All outcome measures were recorded at baseline and at 3 and 6 months post randomisation. Results At 3 months, the intervention group had significantly less leakage 63% v 70%, p=0.002, frequency 30% v 37%, p=0.001, urgency 33% v 40%, p=0.0005 and nocturia 20% v 27%, p=0.0003. At six months the difference was maintained for frequency, urgency and nocturia. There was a significant difference in impact scores relating to activities, feelings, relationships and quality of life between the two groups at three and six months. At three months, the absolute change from baseline in the overall impact scale was calculated as –3.57 (SE 0.13) for the CNP group and –2.65 (SE=0.25) for the GP group resulting in a absolute difference between the groups of –0.92 (95% CI –1.48 to –0.37, p=0.001). Individuals who had had contact with either a GP or CNP during the follow-up period were required to complete a satisfaction questionnaire (91% (2505) of the CNP group and 81% (618) in the GP group). 92% of individuals in the CNP group reported satisfaction with the service generally compared to 77% in the GP group (p<0.0001). Cost–effectiveness analysis indicated a cost per symptom alleviated (NHS costs) of £251 (exchange rate March 2003: 1 GBP = 1.45770 Euro) at 3 months. Conclusions The nurse led intervention reduced the symptoms of incontinence, frequency, urgency and nocturia at 3 and 6 months, impact was reduced and satisfaction with the new service was high. Long term follow-up of the intervention is crucial to establish whether improvements in symptoms persist over time. References 1. Authors names removed to maintain anonymity. Educational preparation for specialist practice in continence care. British Journal of Nursing, 8:18; 1198-1207, 1999 2. Authors names removed to maintain anonymity. Good practice in continence care: The development of evidence-based protocols for a new nurse-led service. British Journal of Nursing, 11:8; 548-559, 2002 3. Authors names removed to maintain anonymity. Validity and reliability of a questionnaire to measure the severity of lower urinary tract symptoms of storage abnormality. British Journal of Urology International 2002 90:205-215 4. Authors names removed to maintain anonymity. Validity and reliability of a questionnaire to measure the impact of lower urinary tract symptoms on quality of life: the Leicester Impact Scale. Neurourology and Urodynamics. 2003. (in press)

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55 Marschall-Kehrel A1, Mürtz G2, Kramer G3, Jünemann K4 1. Urology Consultant, Oberursel, Germany, 2. Apogepha Arzneimittel GmbH, Dresden, Germany, 3. Berufsgenossenschaftliche Unfallklinik, Murnau, Germany, 4. Department of Urology and Pediatric Urology, University of Kiel, Germany A SUGGESTED TREATMENT ALGORITHM IN NOCTURNAL ENURESIS WITH EMPHASIS ON PARTIAL RESPONDERS Aims of Study DDAVP and enuresis alarm are the mainstays of treatment in nocturnal enuresis (PNE) (1). However, these monotherapeutic strategies (2) often have only partial success in PNE. Therefore this retrospective analysis evaluated whether a combination treatment could improve outcomes. Methods PNE children were investigated according to ICI-standards (3) and submitted to a therapeutic strategy as depicted in figure 1.

Outcome was the elimination or reduction of wet nights. The minimum follow-up of the patients was 3 months up to 6 years. As preliminary therapy the urotherapy (4) (timed drinking and modifying of micturition habits) was applied for two weeks . Non-responders then were assigned to DDAVP treatment (0.2 mg/night) for additional two weeks. The dosage was increased up to 0.4 mg/night for two weeks, if the children still were wetting. After 4 weeks of DDAVP the patients were grouped according to their treatment response in this first treatment period. For complete responders a stepwise dose interval reduction scheme keeping the dosage constant (every 2nd day, twice a week, once a week) was performed for two-weeks periods. In cases of relapse the patients were re-assigned to the prior treatment step. In cases of successful dose reduction treatment was stopped.

1st treatment period 2nd treatment period

Nonresponder specializedmanagement

Complete responder

DDAVP stepwisedose reduction

DDAVP 1st

treatment periodextended

Psychotherapy

Partial responder

Anticholinergics

BFB

Alpha-blocker

Alarm

PNE:- virginal- treatm. failures

Uro-therapy DDAVP

Re-

eval

u atio

n

ResponderUrotherapy

Treatment Algorithm PNE

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In partial responders, with reduced bedwetting frequency, all patients were re-evaluated and adjuvant treatments were added according to individual symptomatology while continuing the 0.4 mg DDAVP treatment (2nd treatment period): 1. Anticholinergics (propiverine 0.4 mg/kg b.w.) were applied (5) when nocturnal diuretic volume still

exceeded the individual functional bladder capacity (6). 2. Biofeedback was utilized in children with dysfunctional voiding (7). 3. Alpha-blocker (alfuzosin 2.5 mg bid or qd) were given to children with suspected functional bladder

outflow obstruction (8). 4. Enuresis alarm was applied in children with small amounts of bedwetting who did not wake up (9). 5. Psychotherapy was performed in children with behavioral disorders. Non-responders were referred to specialized management. Results 259 children were enrolled (1996 – 2002). Demographic characteristics: 92 girls, 167 boys, age range 5 – 17 years. 42 children stopped bedwetting (complete responders) after urotherapy. 136 children had a complete response to DDAVP treatment. 3 patients showed no response and were assigned to specialized management. The 78 partial responders were either assigned to anticholinergics (n=41), biofeedback (n=9), alpha-blocker (n=7), alarm (n=2) or psychotherapy (n=2). 17 patients were satisfied with their partial response and therefore had no further treatment. This combination strategy resulted in another 49 complete responders, 9 patients showed further improvement, in 3 cases bedwetting was not further improved . Conclusions The need for preliminary urotherapy is evident. The described DDAVP monotherapy strategy is more effective than the usual DDAVP treatment module. However, applying adjuvant treatment modules improves the complete response rate up to 88%. Furthermore, the combination strategy in partial responders increases the overall efficacy rates. Non-responders (1.2%) will be referred to specialized management, but many partial responders will gain improvement sufficient to refrain from invasive procedures. References 1. Nijman, R., Butler, R., van Gool, J. D., Yeung, C. K., Bower, W., Hjälmas, K.: Conservative

Management of urinary Incontinence in Children. In: Incontinence. Editors Abrams, P., Cardozo, L., Khoury, S., Wein, A.: 2nd International Consultation on Incontinence, Paris, July 1 – 3 2001. 2nd Edition 2002: 513, 2002

2. Hjälmås, K., Sillén, U. Hanson, E., Kruse, S., Hellström A.L.: Long term treatment with desmopressin of children with primary monosymptomatic nocturnal enuresis – An open multi-center study. Brit J Urol 82: 704-709, 1998

3. Abrams, P., Khoury, S., Wein, A. (eds) Incontinence 2nd Edition, Health Publication Ltd, Plymouth, 1086-1089, 2002

4. Kruse, S., Hellström, A.-L., Hjalmas, K.: Daytime Bladder Dysfunction in Therapy-Resistant Nocturnal Enuresis. Scand J Urol Nephrol, 33: 49, 1999

5. Czione, P., Arena, F., Biraghi, M., Cigra, R., Chendi, D., Chiorza, M. et al.: Nocturnal Enuresis and Daytime Wetting: A Multicentric Trial with Oxybutynin and Desmopressin. Eur Urol, 31: 459, 1997

6. Hjälmås, K.: Urodynamics in normal infants and children. Scand J Urol Nephrol, Suppl 114: 20, 1988 7. Yamanishi, T., Yasuda, K., Murayama, N., Sakakibara, R., Uchiyama, T., Ito, H.: Biofeedback Training

for Detrusor Overactivity in Children. J Urol, 164: 1686, 2000 8. Donohoe, J. M., Combs, A. J., Misseri, R., Glassberg, K. I.: Primary bladder neck dysfunction in

children: Results of treatment with alpha-adrenergic antagonists. ICCS & APAPU, Joint Meeting, 10 – 13 December 2002, Hongkong, China

9. Bradbury, M.: Combination therapy for nocturnal enuresis with desmopressin and an alarm device. Scand J Urol Nephrol, Suppl 183: 61 – 63, 1997

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56 Ozkurkcugil C1, Oney E2, Dursun E2, Gokalp A1 1. Department of Urology, Kocaeli University School of Medicine, 2. Department of Physical Medicine and Rehabilitation Kocaeli University School of Medicine IS TRANSDERMAL ELECTRICAL STIMULATION A THERAPEUTIC OPTION WHEN PHARMACOTHERAPY IS INEFFECTIVE IN CHILDREN WITH NOCTURNAL ENURESIS IN ASSOCIATION WITH DAY TIME INCONTINENCE? Aims of Study Overactive bladder in children is the most common cause of nighttimes wetting in association with daytime urinary symptoms such as frequency, urgency and incontinence (1). Bladder training and drug therapy with anticholinergics have been indicated for overactive bladder but some cases are refractory to these therapies. The use of transcutaneous electrical nerve stimulation (TENS) to inhibit detrusor activity in adults is common, and appears to modulate excitatory and inhibitory components of bladder control (2). The aim of this study was to evaluate the result of TENS in nocturnal enuresis in association with daytime incontinence while the other therapies are not curative for enuretic children. Methods Included in our study were 10 girls and 2 boys with a mean age of 9.4 years. All patients had detrusor activity and incontinence refractory anticholinergics. Voiding/incontinence diaries and video-urodynamic studies were applied before the treatment and one month after the last stimulation session. The device for TENS consists of the pulse generator with amplifier and electrodes. One channel of the stimulator was used and 2 electrodes were placed bilaterally over the perianal region (S2-S3 dermatomes). Stimulation of 50 Hz. frequencies and 200-microsecond pulse width is applied for 90 minutes every day during 4±1 weeks. The wilcoxon signed rank test was used for comparison and a p value <.05 was considered significant. Results Before the treatment, all of the children had daytime and night time incontinence. Video-urodynamic studies showed detrusor overactivity in all cases and low-grade vesicoureteral reflux in two patients. 3 of 12 were completely dry after TENS treatment. No improvement was obtained in one of the patients with the treatment. The rest of 8 cases did not report daytime incontinence and their night time incontinence decreased more than 50% (wet in every night versus not more than wet a week). The mean number of voiding/24 hours decreased from 8±3.6 (4-17) to 5.8±1.8 (3-9)(p<0.001) while the mean voided volume/24 hours increased from 118.6±44 (66-191) ml. to 146.3±53.7 (86.5-241) ml (p<0.005) in voiding-chart. Bladder overactivity disappeared in 6 patients urodynamically and improved in 5 cases (mean 53±42 versus 16.45±26.9 cmH20 (p>0.005). No change was observed in mean micturition pressure at peak flow. Vesicoureteral reflux resolved completely a month later with TENS treatment. Conclusions The side effects of anticholinergics or therapy resistance in children have caused to seek other treatment modalities for incontinence due to overactive detrusor. TENS is an attractive treatment due to its noninvasiveness and improvement of symptoms of detrusor overactivity in children. However, further studies are imperative for definitive proof. References 1. Medel,R, Ruarte AC, Castera R et al. Primary enuresis:a urodynamic evaluation. Br J Urol suppl.,81:50,1998 2. Hasan TS, Robson WA, Pridie AK and Neal DE. Transcutaneous electrical nerve stimulation and temporary S3 neuromodulation in idiopathic detrusor instability. J Urol 155:2005-2011,1996.

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57 Kakizaki H1, Tanaka H1, Shibata T1, Moriya K1, Furuno T1, Mitsui T1, Koyanagi T1 1. Department of Urology, Hokkaido University Graduate School of Medicine LONG-TERM OUTCOMES OF LOWER URINARY TRACT FUNCTION IN PATIENTS WITH OCCULT SPINAL DYSRAPHISM: CAN EARLY NEUROSURGERY PROMISE BETTER OUTCOMES IN THE LONG-TERM ? Aims of Study Occult spinal dysraphism (OSD), such as lumbosacral lipoma, diastematomyelia, tight filum terminale, causes the tethered cord syndrome and is often accompanied with lower urinary tract (LUT) dysfunction. In contrast to meningomyelocele that is associated with lumbosacral skin defect, the timing of neurosurgical interventions for OSD is controversial. Although the early neurosurgery for OSD has been recommended to preserve or normalize LUT function, long-term outcomes after early neurosurgery have not been addressed convincingly. We retrospectively analysed the long-term status of LUT function in patients with OSD and compared the outcomes depending on the age at neurosurgery. Methods 37 patients with OSD were divided into 2 groups depending on the age at neurosurgery; less than 2 years in the early surgery (ES) group (15 patients) and 2 years or more in the late surgery (LS) group (22 patients). Mean age at presentation and postoperative follow-up periods were 7 months and 8.3 years in ES group and 9.5 years and 3.8 years in LS group, respectively. OSD was diagnosed because of asymptomatic sacral cutaneous abnormality in 13 (87%) and urinary or neurological symptoms in 2 (13%) in ES group and in 8 (36%) and 14 (64%) in LS group, respectively. Major urinary symptoms in LS group were urinary incontinence, nocturnal enuresis and voiding difficulty. In each patient, LUT function was evaluated with voiding cystourethrography and urodynamics before and serially after neurosurgery. Results In ES group, LUT function before neurosurgery was normal in 12 (80%) and abnormal in other 3 (20%). Of the 12 patients with normal LUT function before neurosurgery, de novo LUT dysfunction after neurosurgery was found in 7 (58%). Of the 3 patients with LUT dysfunction before neurosurgery, LUT dysfunction was improved in 1 (33%) and persisted in the remaining 2. In LS group, LUT function was normal in 10 (45%) and abnormal in other 12 (55%). Of the 10 patients with normal LUT function before neurosurgery, de novo LUT dysfunction after neurosurgery was found in 6 (60%). Of the 12 patients with LUT dysfunction before neurosurgery, LUT dysfunction was improved or normalized in 3 (25%) and persisted in the remaining 9. Thus, in overall, the benefits of neurosurgery (preservation of normal LUT function or improvement of LUT function) were seen in 6 of 15 patients (40%) in ES group and 7 of 22 (32%) in LS group. In 2 patients (one each in ES and LS group) with normal LUT function before and after neurosurgery, long-term deterioration of LUT function was seen 13 to 15 years after neurosurgery. Conclusions Neurosurgery for OSD did normalize or improve LUT function in 25 to 33% of patients with LUT dysfunction irrespective of the age at neurosurgery. However, the present study revealed a relatively high incidence of de novo LUT dysfunction after neurosurgery for OSD (about 60% in both ES and LS groups). The benefits of early neurosurgery for OSD were not confirmed in the present study. Thus, the rationale for early prophylactic neurosurgery in patients with asymptomatic OSD should be reconsidered. In addition, the possibility of long-term deterioration of LUT function should be informed before neurosurgery so that a long-term follow-up will be assured.

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58 Vlajkovic M1, Petronijevic V2, Golubovic E3, Ilic S1, Rajic M 1, Bogicevic M1 1. Dept of Nuclear Medicine, Clinical Center Nis, 2. Clinic of Physical Medicine, rehabilitation and prosthetics, Clinical Center Nis, 3. Clinic of Pediatrics, Clinical center Nis INDIRECT RADIONUCLIDE CYSTOGRAPHY VOIDING PATTERNS IN CHILDREN WITH PRIMARY VESICOURETERAL REFLUX: COMPARATIVE STUDY Aims of Study There is increasing evidence of association between urinary tract dysfunction and primary vesicoureteral reflux (VUR). Radionuclide evaluation of renal function and ureterovesical valve competence in children with risk factors for VUR is now well accepted and indirect radionuclide cystography (IRNC) following dynamic renal scintigraphy may be easily performed. However, the radionuclide evaluation of lower urinary tract dysfunction (LUTD) has not been well established. The aim of this study was to evaluate bladder function by means of IRNC in children with VUR and to investigate whether radionuclide method can distinguish children with voiding dysfunction. Methods The study enrolled 74 neurologically intact children, 14 boys and 60 girls, aged between 2-14 years, in whom VUR were documented using contrast micturating cystouretrography performed as initial method, followed by IRNC using 99mTc-diethilene triamine penta-acetate (DTPA). Aaccording to the urodynamic findings three groups were formed: Group with VUR and normal urodynamic finding (n=27), Group with VUR and detrusor overactivity (n=43), Group with VUR and dysfunctional voiding (n=4). Control group was made of 64 healthy children, 2-13 years old, without any symptoms of LUTD. The dynamics of the bladder emptying were studied after intravenous injection of 37 MBq/10kg/b.w. DTPA in the posterior view collecting ninety 2-seconds frames during voiding (3,4). The parameters evaluated were: voided urine volume (VV), functional bladder capacity (FBC), residual urine ( RU), voiding time (VT), average flow rate (AFR), peak flow rate (PFR) and ejection fraction (EF). Results Table 1 shows IRNC bladder function parameters obtained by means of IRNC in children with VUR regarding the urodynamic diagnosis. Table 1. Radionuclide bladder function parameters in children with VUR regarding the urodynamic diagnosis. Groups No VT

(s) RU (%)

FBC (%)

AFR (ml/s)

PFR (ml/s)

EF (%)

CG 64 22±6 6±3 108±13 12±4 21±5 95±3

VUR-normal finding

27 30±7 b 12±8 96±16 9±2 b 14±3 a 86±8 a

VUR- detrusor overactivity

43 29±15 b 16±12 a 80±37 a 5±3 a,c 8±4 a,c 74±11 a,c

VUR-dysfunctional voiding

4 34±16 29±18 a,d 124±25 a 8±4 b 14±8 b 78±24 b

CG, control group; VUR, vesicoureteral reflux; vs. CG, ap<0.001, b p<0.01; vs. VUR-normal finding, c p<0.001, dp<0.05; VT, voiding time; RU, residual urine; FBC, functional bladder capacity; AFR, avarage flow rate; PFR, peak flow rate; EF, ejection fraction Children with VUR and normal urodynamic findings found to have normal FBC, while values for VT, AFR, PFR and EF were slightly, but significantly decreased regarding the controls. The most prominent reduction of FBC was detected in group with VUR and bladder overactivity, with markedly decreased values for AFR, PFR and EF even in respect to children with VUR and normal urodynamic finding. Children with VUR and dysfunctional voiding were detected to have normal values for VT, but significantly higher FBC regarding the control group. Although slightly lower comparing the controls, mean values for AFR, PFR and EF did not

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differ significantly in respect to children with VUR and normal urodynamic finding. Mean values for RU were higher in all children with VUR. However, while children with VUR and normal urodynamic finding found to have higher RU but without reaching the statistical significance, children with VUR and detrusor overactivity and dysfunctional voiding detected to have markedly increased RU regarding the controls. Three types of radionuclide voiding patterns could be separated in children with VUR. Normal radionuclide voiding pattern is characterized by normal FBC and near normal value for EF and PFR. Markedly low FBC with significantly reduced PFR and EF values were found in children with VUR and overactive bladder, while higher bladder volume with almost normal PFR and slightly lower or near normal EF were detected in children with VUR and dysfunctional voiding. Conclusions This study has confirmed the association between LUTD and congenital VUR. Indirect radionuclide cystography was found as a simple, noninvasive method, performed in physiological manner which allows a reliable separation of voiding patterns in patients with VUR and can be used as a first-line method in detection voiding dysfunction not only in children with VUR but in all children with urinary tract infection. References 1. Vlajkovic M, Bogicevic M, Rajic M, Ilic S, Slavkovic A, Stefanovic V, Artiko V. Radionuclide voiding

pattern in children with unstable bladde. Nuc Med Review 2000; 3: 53-56. 2. Vlajkovic M, Ilic S, Bogicevic M, Rajic M, Ristic L, Petronijevic V, Golubovic E, Stefanovic V, Artiko V.

Radionuclide voiding patterns in children with vesicoureteral reflux. Eur J Nucl Med. DOI 10.1007/s00259-002-1077-x

59 Pesce F1, Prezioso D 2, Zattoni F 3, Artibani W 4, Tubaro A 5, Scarpa R M6, Rizzi C A7 1. Policlinico G. Rossi, Verona-Italy, 2. Policlinico Federico II, Napoli- Italy, 3. Az. Ospedaliera S. Maria della Misericordia, Udine -Italy, 4. Policlinico G. Rossi, Verona- Italy, 5. Ospedale S. Andrea, Roma - Italy, 6. Ospedale di Orbassano, Torino- Italy, 7. Boehringer-Ingelheim Italia, Milano - Italy SYMPTOMS AND BOTHER OF FEMALE PATIENTS PRESENTING WITH LUTS IN UROLOGY CENTRES IN ITALY: FIRST EVALUATION FROM THE FLOW STUDY Aims of Study The FLOW study (Female LUTS: Observational study in Women) is a 2-year non-interventional investigation - currently ongoing - aimed at evaluating the clinical profile and the diagnostic and therapeutic management of Italian women presenting with LUTS in Urology Outpatients Clinics. The present work reports on patients characteristics and their management on the basis of freely chosen procedures in each centre. The relative frequency of LUTS, the related bothersomeness and their impact on the quality of life were evaluated by means of two questionnaires: the W-IPSS and the ICIQ-LF. Their validation process is matter of another work which is presented separately. Methods Patients (age 18 years, negative dipstick) suffering from LUTS from at least 3 months , and regarded to be compliant with questionnaire compilation, were consecutively enrolled in 36 Italian Centres of Urology. They underwent a urological visit according to the routine procedures used at each centre. The only procedure prescribed by the protocol was the self-administration of two questionnaires: the ICIQ-LF (ICI Questionnaire – Long Form) and the W-IPSS (International Prostate Symptom Score, adapted for women: the QoL single question refers to urinary symptoms generically, in spite of the specific reference to prostatic disease of the original IPSS). The present paper reports on data related to 750 patients.

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Results The mean (SD) age of the enrolled women was 54 (14) year and the large majority of patients (86%) was new to the Centers. Patients were self-referred in a significant percentage of cases (30%). The presence of LUTS (with or without a definite diagnosis) had been previously recognised in 38% of patients. Of the laboratory assessments, urinalysis and urine culture were the most commonly performed procedures (97 and 90% respectively), whereas ultrasonography was the most commonly performed instrumental test (81%). An urodynamic evaluation was carried out in 48% of patients. The pad weight test was used in 5% of cases only. Interestingly, urinary diary was used sparingly (34%) despite the fact that most patients suffered from storage symptoms and incontinence. In general, the approach for newly diagnosed LUTS was similar also for previously diagnosed LUTS. The 5 most frequent symptoms were: daytime frequency (71%), urgency (69%), urinary incontinence (67%), nocturia (59%) and feeling of incomplete voiding (52%). Of 493 patients suffering from urinary incontinence, 39% showed symptoms of stress incontinence, 31% of mixed incontinence and 28% of urge incontinence. Overall, storage symptoms were clearly predominant (97%) but voiding symptoms were relatively common too (62%). The mean (SD) score of the bother for all symptoms detected with ICIQ-LF QoL was 5.6 (3.2) in a scale of 0 to 10. The degree of bother corresponded closely to LUTS intensity. The mean W-IPSS score and the mean single question QoL score were 12.4 and 4.1 respectively and a significant association was detected between them (r=0.43; p<0.0001). When the classical classification of IPSS used for the assessment of BPH symptoms was applied to W-IPSS, the frequency of mild (0-8), moderate (9-18) and severe (19-35) LUTS was 27, 50 and 17% respectively. Fifty percent of the enrolled patients had previously been treated with non-pharmacological approaches and 18% with drugs, these latter consisting mainly of anticholinergics (47%). During the current visit, pharmacological treatment was prescribed to 34% of patients and non pharmacological (behavioural and neuromodulation) to 35%. Surgery was indicated to 16% of women. Non-pharmachological approaches were more frequently prescribed in patients with urinary incontinence (36%) and urinary retention (54%), while drug treatment prevailed in those with dry and wet overactive bladder (44%) and in those with chronic pelvic pain (33%). Interestingly, while anticholinergics were used in 49% of OAB-dry patients, they were prescribed to 81% of those with OAB-wet. Conclusions There are few data on the prevalence of LUTS in Italian women. The present study is currently investigating the universe of female LUTS as they are managed in urology settings. There is a relevant percentage of female patients who self-refer to this specialist without previous clinical assessment. Although storage symptoms are the most common, as expected, a relevant proportion of patients shows also voiding symptoms. In general, bothersomeness and intensity of symptoms are well correlated. The most frequent diagnosis is urinary incontinence, in the large majority of cases with stress or mixed symptoms. Pharmacological and behavioural therapies are given in equal proportion (more than 30%), while surgery is prescribed to one sixth of the female LUTS population. The follow-up visits at 1- or 2-year will allow to evaluate the evolution of the diseases and the appropriateness of treatments.

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60 Hannestad Y1, Lie R T2, Rortveit G1, Hunskaar S1 1. Section for General Practice, Dept of Public Health and Primary Health Care,University of Bergen, 2. Section for Medical Statistics, Dept of Public Health and Primary Health Care,University of Bergen FEMALE URINARY INCONTINENCE – RUNNING IN THE FAMILY? Aims of Study Preliminary evidence suggests that genetic factors may play a role in the development of urinary incontinence. The aim of this study was to estimate the recurrence risk of incontinence among daughters, granddaughters and sisters of incontinent women compared with the risk for relatives of continent women. Methods 27936 women with data on incontinence comprise the basic study population of the Norwegian EPINCONT Study. By means of the kinship registry from Statistics Norway we could map the familial relations within the study population. Three different cohorts were established to follow recurrence from mother to daughter and from a sister to subsequent sisters. The first cohort consisted of 6021 mothers and their 7629 subsequent daughters. A mother could contribute with information on recurrence in several daughters and could also appear as the daughter of her own mother in our data. The second cohort consisted of 332 mothers who could be followed with respect to recurrence both in a daughter and in a granddaughter. The third cohort consisted of 2104 older sisters followed to eventual recurrence in a younger sister. 322 sisters could be followed to two younger sisters. A severity index was calculated based on the answers regarding frequency and amount of leakage, and the incontinence was categorised into slight, moderate and severe.The incontinence was also classified into the types stress, urge and mixed incontinence. We compared the risk of incontinence in the daughters of the incontinent mothers with the risk in the daughters of the continent mothers. We also compared the risk of incontinence in the subsequent sisters of the incontinent older sisters with the risk in the subsequent sisters of the continent older sisters. In the cohort of three generations we investigated the recurrence of incontinence in granddaughters with respect to the combined incontinence status of the two older generations. The effects were estimated by the odds ratio with corresponding 95% confidence intervals from logistic regression analyses. Continent women served as the reference group. Subanalyses were performed for the different types and degrees of severity of incontinence. In the following text we give the adjusted results from the logistic regression analyses. Age, body mass index and parity weakly confounded the effect estimates and were included in the final models for all cohorts. No interaction was found. Results Daughters of mothers with any incontinence had an odds ratio of 1.4 (95 % CI 1.3 to 1.6) of being incontinent. If the mother had severe incontinence, the odds ratio for recurrence of severe symptoms in the daughter was 2.2 (95 % CI 1.4 to 3.3). The risk for severe incontinence was also raised among the daughters when the mothers had any incontinence (Odds ratio 1.8, 95 % CI 1.3 to 2.5). The odds ratio for daughters of stress- incontinent mothers of having similar type of incontinence was 1.7 (95 % CI 1.4 to 2.1). If the mother had severe stress incontinence the odds ratio was raised to 3.6 (95 % CI 1.4 to 9.5). The odds ratio for specific recurrence of mixed incontinence was 1.7 (95 % CI 1.3 to 2.3), and 2.6 (95 % CI 1.2 to 5.6) for severe mixed type. Due to small numbers the odds ratio of 1.8 (95 % CI 0.8 to 4.1) for urge incontinence was not statistically significant. The incontinence of the grandmothers had only some effect when added to the effect of the mothers’ incontinence in a combination variable. Having two incontinent foremothers led to an odds ratio of 2.9 (95 % CI 1.1 to 7.6) for being incontinent. When we followed older sisters to look for recurrence in younger sisters we found an odds ratio of 1.9 (95 % CI 1.5 to 2.5) for any incontinence in sister 2 and 1.8 (95 % CI 1.0 to 3.4) in sister 3. The recurrence risk of severe symptoms was 1.9, but not statistically significant. Younger sisters of older stress-incontinent sisters had an odds ratio for recurrence of the same incontinence type of 2.2 (95 % CI 1.5 to 3.2) (sister 2) and 2.1 (95 % CI 0.8 to 5.6) (sister 3). The odds ratio for recurrence of mixed incontinence was 2.2 (95 % CI 1.2 to 4.1) and 1.8 (95 % CI 0.4 to 9.1) for sister 2 and sister 3, respectively. No younger sisters of older urge-incontinent sisters had urge incontinence.

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Conclusions Our results indicate the presence of hereditary factors in the development of urinary incontinence in women. We found an increased risk for any incontinence, stress and mixed type and severe symptoms for women whose mothers or older sisters were incontinent. For daughters of incontinent mothers an incontinent grandmother raised the risk further. 61 van Brummen H J1, Heintz P1, van der Vaart H1 1. University Medical Center Utrecht HOW BOTHERSOME ARE LUTS DURING PREGNANCY? Aims of Study Lower urinary tract symptoms (LUTS) are in particular common during pregnancy and the prevalence increase with increasing gestation till term. It is largely unknown how much women are bothered by these symptoms during their pregnancy. Therefore, the objective of this study was to report on the prevalence of LUTS during pregnancy and to evaluate the amount of bother women experiences from these LUTS. Methods At 12 weeks gestation, 293 nulliparous women were recruited from eight midwifery practices in the Netherlands. They took part in a prospective longitudinal cohort study on the effects of pregnancy on pelvic floor function. The study was approved by the Medical Ethics Committee of the University Medical Center Utrecht. The women signed an informed consent. The women received three self-report questionnaires during pregnancy the first at 12 weeks gestation, the second at 24 weeks gestation and the third at 36 weeks gestation. Urogenital symptoms were measured with the Dutch version of the Urogenital Distress Inventory (UDI). (1,2) This questionnaire contains of 10 questions about micturition symptoms and the experienced level of discomfort of these symptoms. Each item measures if a symptom is present and the amount of bother the woman experiences from that symptom. The LUTS symptoms were assessed according to the recommendations of the ICS, and in concordance with other studies. Bothersome LUTS was defined as reporting moderately or greatly bother from the symptom. Women with LUTS who were not at all or slightly bothered by it were regarded as not having bothersome LUTS. The statistical analysis was done in SPSS 10.0 for Windows. Results At 12 weeks gestation 263 (90%) of the women had at least one LUTS, at 24 weeks 284 (97 %) and at 36 weeks 281 (96%) of the women had one or more LUTS. The prevalence of LUTS at 12, 24 and 36 weeks gestation is shown in Table 1. Table 2 shows the prevalence of bothersome LUTS at 12,24 and 36 weeks of pregnancy. Conclusions Symptoms of LUTS occur in almost all women during pregnancy. Whereas the prevalence of urgency/frequency is stable from 12 weeks gestation on, the prevalence of true incontinence symptoms increases with gestational age. Despite the high prevalence of symptoms the majority of women report not to be bothered by it. Remarkably, symptoms of frequency/urgency are more often regarded as bothersome as compared to true urinary incontinence symptoms. Table 1 Period prevalence of LUTS during pregnancy

12 weeks 24 weeks 36 weeks Frequency 220 (75) 239 (82) 240 (82) Urgency 181 (62) 193 (66) 200 (69) Stress incontinence 55 (19) 123 (42) 132 (45) Urge incontinence 18 (6) 41 (14) 61 (21) Difficulty emptying bladder 48 (16) 78 (27) 90 (31) Feeling of incomplete emptying 103 (35) 149 (51) 149 (51)

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The values are numbers (percentage) Table 2 Bothersomeness of LUTS during pregnancy

12 weeks 24 weeks 36 weeks Frequency 47/220 (21) 57/239 (24) 67/240(28) Urgency 40/181 (22) 44/193 (23) 37/200(19) Stress incontinence 7/55 (13) 19/123 (15) 21/132(16) Urge incontinence 2/18 (11) 10/41 (24) 12/61 (20) Difficulty emptying bladder 6/48 (13) 17/78 (22) 21/90 (23) Feeling of incomplete emptying 9/103 (9) 25/149 (17) 21/149 (14) The values are numbers (percentage) References 1) Schumaker SA, Wijkan JF, Uebersax JS, McFlish D, Fantl A. Health-related quality of life measures for women with urinary incontinence: the Incontinence Impact Questionnaire and the Urogenital Distress Inventory. Continence Program in Women (CPW) Research Group. Qual Life Res. 1994 Oct;3(5):291-306 2) Van der Vaart C.H.,de Leeuw JRJ, Roovers JPWR, Heintz APM. Measuring health-related quality of life in women with urogenital dysfunction: The urogenital distress inventory and incontinence impact questionnaire revisited. Neurourol Urodyn. 2003;22(2):97-104. 62 Mueller E 1, Latini J 2, Lux M2, Stablein U 1, Brubaker L1, Kreder K 2, FitzGerald M P 1 1. Loyola University Medical Center, 2. University of University of Iowa Medical Center GENDER DIFFERENCES IN 24-HOUR URINARY DIARIES OF ASYMPTOMATIC ADULTS. Aims of Study Voiding diaries are commonly used to evaluate patients with lower urinary tract symptoms, and are less prone to recall bias than questionnaires concerning urinary frequency. There is little published information about the voiding habits of asymptomatic adults; in particular, it is not known whether there is any gender difference in those voiding habits. Our aim was to determine whether there were any important gender differences in the voiding habits of aysmptomatic adults, as reported in 24-hour frequency-volume diaries. Methods The 24-hour urinary diaries of asymptomatic men were compared with those of age- and race-matched asymptomatic women. Diary variables included total urinary frequency, total intake, voids per liter intake, total voided volume, maximum and mean voided volumes, daytime and nighttime diuresis rates. We used multivariate linear regression and logistic regression to determine the effect of gender on diary variables, with results considered significant at the 5% level. Results We included a total of 284 diaries from subjects aged 18-68. Males and females had similar body mass indices. Subjects were 56% African American, 31% Caucasian, 8% Asian and 6% Hispanic. Linear regression analysis determined that in females, 24 hr urinary frequency was greater, mean voided volume was lower and the number of voids per liter intake was greater. Males had a higher fluid intake (see Table of mean +/- standard deviation, range, below).

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Diary variable Females

(n=142) Males (n=142)

P value

Total voids / 24 hours 8.2 +/- 2.3 (4-18) 7.6 +/- 2.7 (3-21) < 0.01 Mean voided volume (mL) 210 +/-90

(53-533) 251 +/- 126 (90-1350)

< 0.01

Maximum voided volume (mL) 364 +/- 181 (90-870)

404 +/- 216 (90-1350)

0.22, NS

Total fluid intake (mL) 2061 +/- 771 (625 – 3960)

2854 +/- 1450 (960-10520)

<0.001

Voids per liter intake 4.4 +/- 1.7 (1.5–10.7)

3.1 +/- 1.3 (0.6-8.3)

<0.001

Record of any nocturic episode 44% 39% P = 0.3, NS Conclusions The results of this preliminary study of asymptomatic North American adults suggest that there are significant gender effects on 24-hour urinary diary variables. These differences should be borne in mind when using diaries clinically, and in the design of research studies. 63 Seim A1, Hoyo C2, Ostbye T 2, Vatten L 1 1. Norwegian University of Science and Technology, Dept. of Community Medicine and General Practice, 2. Duke University Medical Center, Dept. of Community and Family Medicine PREVALENCE AND CORRELATES OF NOCTURIA IN MEN – A LARGE COMMUNITY BASED STUDY Aims of Study Nocturia is a condition where the individual has to wake up at night one or more times to void.(1) Until recently, nocturia in men was regarded principally as a problem related to prostatic enlargement, but is now increasingly recognized as a clinical entity in its own right. Due to different population samples and definitions, prevalence estimates have varied. Our objective was to establish prevalence estimates of nocturia in a total community population of approximately 30,000 men, and investigate and quantify how the prevalence varies by different definitions. We also wanted to identify factors that correlate with nocturia. Methods This study is part of a comprehensive health study (HUNT 2) that was conducted in a county in Norway from 1995 to 97. All citizens 20 years and older were invited, and the overall participation was 70%. A self-administered questionnaire included demographic variables, lifestyle factors, current medications, and urinary history (including questions about nocturia and prostatic enlargement). Self-reported prostatic enlargement was ascertained in two ways: either having been told by a doctor that the prostate was enlarged, or having undergone surgery of the prostate due to hyperplasia. Clinical measurements, including blood pressure and waist/hip ratio, were also performed. Prevalence estimates for nocturia were calculated using three different definitions; having to get up to void (1) one or more, (2) two or more, or (3) three or more times at night. Relevant variables from the health survey were included in logistic regression analyses to identify correlates for nocturia that may also be risk factors for the condition. Using the three definitions of nocturia separately as outcome variables, independent variables included age, life style factors (smoking, alcohol, coffee, physical activity), use of antihypertensive medication, systolic blood pressure, waist/hip ratio, and self-reported prostatic enlargement.

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Results Figure 1. Prevalence of nocturia according to definitions and age groups in 23 220 men. Nocturia>=1: All 3 stacked bars ((Noct.=1)+(Noct.=2)+(Noct.>=3)). Overall prevalence: 52.7% Nocturia>=2:Two lowest stacked bars ((Noct.=2)+(Noct.>=3)). Overall prevalence: 19.0% Nocturia>=3: Lowest bar. Overall prevalence: 8.4% 30,556 men returned the questionnaire, and 23,220 (75.9 %) had answered questions about nocturia. Prevalence estimates for nocturia according to the three different definitions are shown in Figure 1. Regardless of definition, the prevalence of nocturia increased gradually with increasing age. Results from multiple logistic regression analyses are shown in Table 1. In addition to age, important independent correlates of nocturia were prostatic enlargement, and to a lesser extent use of antihypertensive drugs. A weak, but statistically significant association was noted with waist/hip ratio. Nocturia risk was inversely associated with systolic blood pressure and smoking. Using different definitions of nocturia did not materially change these results. Coffee consumption was associated with the lowest level of nocturia, while there were no significant association with physical activity and use of alcohol.

Table 1. Results from multiple logistic regression analyses, Odds Ratio (95% confidence intervals). Reference category: a Age group 20-29; b Waist/hip ratio < 0.851 Dependent variables Independent variables Nocturia >=1 Nocturia >=2 Nocturia >=3 Age groupsa 30-39 1.18 (1.04-1.33) 1.17 (0.98-1.40) 1.35 (1.06-1.73) 40-49 1.88 (1.67-2.10) 1.79 (1.52-2.11) 2.01 (1.60-2.53) 50-59 3.36 (2.98-3.79) 2.05 (1.73-2.43) 2.10 (1.67-2.66) 60-69 5.40 (4.72-6.17) 2.09 (1.75-2.50) 1.67 (1.30-2.15) 70-79 6.52 (5.62-7.56) 2.31 (1.92-2.80) 1.36 (1.03-1.78) 80-89 8.30 (6.52-10.55) 3.41 (2.69-4.32) 2.07 (1.48-2.90) >= 90 33.8 (4.99-228.9) 6.32 (2.77-14.44) 3.74 (1.43-9.78) Waist/hip ratio (quintiles)b 0.851-0.881 1.09 (0.99-1.20) 1.11 (0.98-1.26) 1.18 (0.99-1.39) 0.882-0.906 1.06 (0.96-1.17) 1.02 (0.90-1.16) 1.04 (0.87-1.23) 0.907-0.942 1.05 (0.95-1.16) 1.07 (0.94-1.21) 1.04 (0.88-1.24) >0.942 1.31 (1.18-1.45) 1.34 (1.18-1.51) 1.23 (1.03-1.46) Prostatic enlargement 2.16 (1.91-2.45) 2.24 (2.01-2.50) 2.01 (1.72-2.34) Syst. blood pressure >=150 0.90 (0.84-0.97) 0.85 (0.78-0.93) 0.81 (0.71-0.91) Antihypertensive drugs 1.40 (1.25-1.56) 1.32 (1.18-1.47) 1.22 (1.04-1.43) Smoking 0.83 (0.78-0.89) 0.85 (0.78-0.93) 0.86 (0.76-0.97) Coffee >= 5 cups/day 1.10 (1.04-1.17) 1.03 (0.96-1.11) 0.95 (0.85-1.05) Alcohol 0.91 (0.81-1.02) 0.89 (0.78-1.01) 0.92 (0.77-1.11)

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Conclusions This large study, comprising the total adult population in a county, confirms that nocturia is a highly prevalent condition in men, and that the prevalence increases with age. Any nocturia (nocturia >=1) showed a roughly linear increase with age throughout the life span, while more severe nocturia (>=3) was relatively stable through young and middle age, but increased markedly in the older age groups. From a clinical point of view, this prevalence study does not directly address how many men are in need of treatment, as specific questions about bothersomeness were not included. Not surprisingly self-reported prostatic enlargement was a significant predictor for nocturia, even if nocturia has been recognized as a clinical entity and not only as a result of hyperplasia of the prostate. The negative association between smoking and prevalence of nocturia was notable, as was the negative association with blood pressure. These findings should warrant further investigations. References 1. Van Kerrebroeck P et al. The standardization of terminology in nocturia: report from the standardization subcommittee of the International Continence Society. BJU Int 2002;90 Suppl 3:11-5. 64 Huang Foen Chung J W N C1, van Mastrigt R1 1. Department of Urology, Sector Furore, Erasmus MC CORRELATION OF NON-INVASIVE URODYNAMICS WITH IPSS AND PROSTATE VOLUME Aims of Study In a longitudinal survey of changes in urinary bladder contractility secondary to benign prostatic enlargement (BPE) 1300 volunteers will be studied [1]. In this study, the IPSS is self administered, the prostate volume is assessed, the free flowrate is determined and the isovolumetric bladder pressure is non-invasively measured. This report describes the correlation of these parameters based on results of the first 577 completely investigated males. Methods Volunteers, patients invited by general practioners, as well as colleagues from the Erasmus MC invited by email, took part in this study. Inclusion criteria were age 38-77, informed consent, and ability to void in the standing position. Men with any heart condition or history of heartfailure ever, known neurological condition, such as Parkinson's disease, previous surgery of the lower urinary tract (LUT), anticoagulating and or LUT drug use were excluded. In all cases the investigator decided on the basis of anamnesis and physical examination whether a man could enter the study. Thus far, 577 subjects were examined. First, the IPSS, including the quality of life (QoL) score, was completed and then the prostate volume was assessed by transabdominal ultrasonography. Subsequently a free flowrate measurement was done. If the maximum flowrate exceeded 5.4 ml/s, the isovolumetric bladder pressure was non-invasively measured using the condom catheter method [2]. The urethral resistance was provisionally calculated as the maximum condom pressure minus 5.8 times the maximum free flowrate minus 36.4. On the basis of a provisional method [3] for definition of obstruction using a diagram of the maximum condom pressure versus the free flowrate, the urethral resistance was classified. A high flowrate combined with a low condom pressure gave a negative result of the formula and was classified as a low urethral resistance. Contrary, a low flowrate with a high condom pressure or positive formula value was classified as a high urethral resistance. For the comparison with other studies, the IPSS was stratified in an irritative (sum of the answers to questions (q) 2, 4, and 7, i.e., storage symptoms) and an obstructive (sum of the responses to q1, 3, 5, 6, i.e., voiding symptoms) score. Results In this study the total IPSS ranged from zero to 26 with a mean of 6, and a standard deviation (SD) of 5, whereas the prostate volumes ranged from 8 to 140 ml with a mean of 33 ml, and an SD of 18 ml. In detail, the irritative score ranged from zero to 16 with a mean of 2.7 and an SD of 3.2, whilst the obstructive score

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ranged from zero to 14 with a mean of 3.5 and an SD of 2.5.Based on the provisional formula 28 percent (159/577) of the men had a non-invasively documented high urethral resistance. Subjects with a high urethral resistance, closed circles in the figure, had a significantly higher total IPSS (7.4±5.4) than those with a low urethral resistance (total IPSS (5.7±4.6)), open circles. Mann-Whitney U-test: p<0.001, N=577. In fact, all separate scores of the IPSS, and the QoL score were significantly different between both groups, except the scores for frequency (q2) and nocturia (q7). The total IPSS and the urethral resistance were also significantly correlated, Spearman's rho ( )= 0.21, p<0.001. With the exception of the score for nocturia (q7), the different scores and the QoL score were significantly correlated with the urethral resistance too. Therefore, the total obstructive score, =0.16, p<0.001, and the total irritative score, =0.11, p=0.01 were also significantly correlated with theurethral resistance. On the other hand, a significant difference in the prostate volumes, which were 35±20 ml in the high urethral resistance group versus 33±17 ml in the low urethral resistance group was not found, Mann-Whitney U-test: p=0.49, N=577, and prostate volumes and the urethral resistance were not significantly correlated, = 0.03, p=0.45.

Conclusions Two studies in the literature reported no correlation between invasive pressure flow parameters and the IPSS. In the first [4], a correlation between the obstructive score and the degree of urodynamically proven Bladder Outlet Obstruction (BOO) in 91% of the subjects studied could not be identified. In the second [5], where the Abrams-Griffiths nomogram definition of obstruction was used, no significant correlation between pdetQmax and IPSS was found. As no IPSS stratification was mentioned, we assumed the total score was used. Additionally, a modest but statistically significant correlation was found between pdet.Qmax and prostate volume, supporting the hypothesis that prostate size is a contributing factor in symptomatic BPH. That was not the case in our present study, probably because our male population was not suffering from BPH, or BPE more precisely. The non-invasive urodynamic data in this study were significantly correlated with the complaints as quantified by the IPSS. This (re)illustrates the value of the condom catheter method for non-invasive urodynamics. References [1] Neurourol Urodyn 2002; 21(4): 351-352. [2] J Urol 2001; 165: 647-652. [3] Neurourol Urodyn 2002; 21(2): 117-125. [4] Neurourol Urodyn 1999; 18(3): 173-182. [5] Neurourol Urodyn 1999; 18(1): 17-24. Acknowledgements This study was supported by the Dutch Kidney Foundation (PC85), and the foundations "Vereniging Trustfonds Erasmus Universiteit", "Stichting Bevordering Volkskracht" and "Stichting Aelwijn Florisz".

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65 Griffiths D1, Derbyshire S 1, Logue E 1, Stenger V A 1, Resnick N 1 1. University of Pittsburgh CEREBRAL CONTROL OF BLADDER FUNCTION: THE BRAIN-BLADDER CONNECTION Aims of Study In urge incontinence, urodynamic investigation typically reveals detrusor overactivity. Treatment is then targeted at the detrusor, usually without knowledge of etiology and with variable success. Urge incontinence and detrusor overactivity, however, indicate an inability of the brain to volitionally control the voiding reflex. Functional brain imaging may offer new understanding of normal and abnormal bladder control and, ultimately, improved treatment. Previous work, including functional imaging of the human brain by positron emission tomography (PET), has identified many brain regions concerned with normal bladder filling and voiding, but their functions remain unclear. To identify brain regions specifically involved in failure of bladder control, we compared brain activation in subjects with and without detrusor overactivity, monitored by cystometry, during functional magnetic resonance imaging (fMRI). fMRI is a rapid brain imaging technique that can monitor changes associated with detrusor contraction. Its hostile magnetic environment and low signal-to-noise ratio however present technical challenges. The aims of this study were thus: to prove the feasibility of combining brain fMRI with simultaneous urodynamics; to delineate brain behavior during bladder filling; and to seek differences in brain response to bladder filling among subjects with and without detrusor overactivity. This abstract reports results from the first few subjects. Methods Subjects were of either sex, older than 20 y, and without evident neuropathy. Bladder control problems were not an exclusion criterion. After comprehensive assessment, including dual-channel urodynamics, scanning was performed with the subject supine in a 3T GE machine, using a standard head coil. Following structural imaging, a spiral scanning protocol was used to determine blood-oxygen-level-dependent contrast, representing neuronal activity. The whole brain was scanned once every 1.5 s, at a resolution of approximately 3 mm, while intravesical pressure was measured and saline solution was pumped in or out of the bladder through two 8-French transurethral catheters, connected via 10-meter stiff-walled tubes to remote urodynamic equipment. Strong desire to void was signaled by push button. Abdominal pressure was not measured, as it varied little and bladder behavior was already known. To improve the signal-to-noise ratio, repeated blocks of imaging and measurements were performed. Each block started with 10.5 s rest, followed by rapid infusion of 30 ml saline into the bladder in 10.5 s, a pause for 10.5 s, and then withdrawal of 20 ml in 10.5 s. This series was repeated 4 times within a block. By infusing more than was withdrawn we repeatedly evoked and abolished sensation without accommodation. Because responses to changes of bladder volume and sensation may differ, we performed measurements at a target volume of 100 ml (2 blocks, evoking little sensation), and again after filling the bladder at 60 ml/min to strong desire to void (2 to 4 blocks, evoking strong sensation). The functional images were reoriented into standard stereotactic space and the responses relative to rest were calculated using standard statistical procedures (SPM2, Wellcome Department of Imaging Neuroscience, UK). Activity during infusion, post infusion, and during withdrawal was compared with rest. Results 8 subjects (7 females and one male, aged 23-83 y) were successfully examined. Claustrophobia and technical problems curtailed measurement in 2 other cases. 5 subjects showed detrusor overactivity, 2 of them during the scanning session. 3 subjects showed no detrusor overactivity and had no symptoms suggestive of it. Activation during and following infusion was demonstrated in the frontal cortex (see figure), the anterior cingulate gyrus, the insula, and the cerebellum in 2 to 5 subjects (P< 0.05, corrected for multiple comparisons over the whole brain). Group analysis indicated both cortical and infra-cortical regions of common activation (P<0.05), and suggested a trend towards a different pattern of activation in the subjects with detrusor overactivity (P=0.08). These results will become firmer as this ongoing project accrues subjects.

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Figure: Bilateral activation in frontal cortex during bladder filling (relative to rest): combined result in 5 subjects. Light areas show significant activations (P<0.05, corrected for multiple comparisons). Conclusions Combination of brain fMRI with simultaneous cystometry is physiologically revealing and technically feasible. Responses to bladder filling in cerebellum, insula, and premotor cortex confirm previous reports. Bilateral activation in the frontal cortex may represent inhibition of voiding in response to bladder filling, consistent with clinical observation of the inhibitory role of this region. A different pattern of brain activity in subjects with detrusor overactivity is suggestive of altered cerebral processing that may reflect poor bladder control. 66 Nuotio M1, Tammela T L1, Luukkaala T1, Jylhä M1 1. University of Tampere URGE INCONTINENCE AS A PREDICTOR OF INSTITUTIONALIZATION IN AN OLDER POPULATION Aims of Study Institutionalization has been suggested as an outcome of urinary incontinence, however, longitudinal data on the subject in random older populations are limited (1,2). The aim here was to examine the predictive significance of urge incontinence in an unselected older population during a 13-year follow-up. Methods A population-based longitudinal survey was conducted involving 366 men and 409 women aged 60 years and over. Urge incontinence was defined as having trouble in getting to the lavatory in time with urinary leakage in the daytime or during the nights. Institutionalization was defined as the date when the person was admitted to a nursing home or to a hospital providing long-term care. Long-term care involved only cases where the person did not return to ordinary home. In the analyses, time was counted up to the date of death for those who died at home and to the end of the follow-up period for those who survived living at home. Age-adjusted Cox proportional hazards models with RR (relative risks) and 95 % CI (confidence intervals) were used to examine the association of urge incontinence, living arrangements, self-reported neurological, cardiovascular, musculoskeletal and other chronic diseases, ADL (activities of daily living) disability and depressive symptoms with institutionalization. In the multivariate analyses, all the predictors were taken into account simultaneously in order to examine the independent association of urge incontinence with institutionalization. Regarding the differences in the nature of urinary symptoms and living conditions between the two genders, the analyses were conducted separately for men and women. Results The crude prevalence for urge incontinence in men and women were 5 % and 15 %, respectively. During the 13-year follow-up, 13 % of the men and 26 % of the women moved into an institution. Of the men 50 %

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and of the women 37 % died before being institutionalized. In the age-adjusted analyses, urge incontinence (RR 3.17; 95 % CI 1.41-7.13), other chronic diseases (RR 2.33; 95 % CI 1.35-4.02), ADL disability (RR 2.04; 95 % CI 1.06-3.89) and depressive symptoms (RR 1.32; 95 % CI 1.12-1.55) predicted institutionalization in men. In women, urge incontinence did not predict institutionalization, but living alone (RR 1.95: 95 % CI 1.24-3.06), cardiovascular diseases (RR 1.63; 95 % CI 1.09-2.44), other chronic diseases (RR 1.46; 95 % 1.00-2.13) and ADL disability (RR 1.80; 95 % CI 1.13-2.89) were significant predictors. In the multivariate analyses, simultaneously adjusted for age and other health and social indicators, age in both men and women (RR 1.15; 95 % CI 1.10-1.19 and RR 1.15; 95 % CI 1.12-1.19, respectively) significantly predicted institutionalization. Urge incontinence remained a strongly significant predictor for institutionalization in men (RR 3.07; 95 % CI 1.24-7.59) and depressive symptoms also showed some predictive power (RR 1.22; 95 % CI 1.00-1.48). In women, in addition to age, living alone was the only independent predictor in the multivariate analysis (RR 1.99; 95 % CI 1.25-3.18). Conclusions Urge incontinence is a significant predictor of institutionalization in men but not in women. The finding may imply that the condition is a marker of more advanced disability in men, but differences in the etiology and psychocial factors may also contribute to the gender difference. Nevertheless, the finding emphazises the importance of interventions aiming at promoting continence and coping with the problem in the clinical practice and whenever community based supportive systems for caregivers are being designed especially in older men. 1) Medically recognized urinary incontinence and risks of hospitalization, nursing home admission and

mortality. Age and Ageing 1997; 26: 367-374. 2) Urinary incontinence as a predictor of death and instituionalization in a general aged population. Arch

Gerontol Geriatr 1995; 21: 307-315. 67 D'amico A1, Pesce F1, Rubilotta E1, Sarti A1, Curti P1, Artibani W1 1. Dept. Urology - Policlinico - Verona CORRELATION BETWEEN DETRUSOR AFTER-CONTRACTION AND OVERACTIVE BLADDER SYNDROME, DETRUSOR OVERACTIVITY AND POST-MICTURITION DRIBBLE Aims of Study Detrusor after-contraction is an urodynamic observation of uncertain significance(1-2). Aim of this study was to assess the prevalence of detrusor after-contraction in patients undergoing urodynamic evaluation and its correlation with overactive bladder syndrome, detrusor overactivity and post-micturition dribble. Methods From a large urodynamic data base we retrospectively evaluated 358 patients (131 males and 227 females) who underwent filling cystometry and flow-pressure study for lower urinary tract symptoms (LUTS), neurological diseases or post-operative follow-up. Methods, definitions and units conform to the standards recommended by the International Continence Society, except where specifically noted. Detrusor after-contraction was considered as a sudden increase in detrusor pressure – regardless of its amplitude – after cessation of voiding detrusor contraction and in the absence of flow. The results were statistically evaluated using Chi-square test with SPSS 10.1 software. P-values <0.05 were considered statistically significant. Results The overall prevalence of detrusor after-contraction was 15.6% (56/358 pts). In the 56 pts with detrusor after-contraction, the prevalence of overactive bladder, of detrusor overactivity and of post-micturition dribble was 76.2% (41/56 pts), 69.6% (39/56 pts) and 26.8% (15/56 pts), respectively. A statistically significant correlation was found between overactive bladder (p< 0.01) and DA-C

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and between detrusor overactivity and detrusor after-contraction (p<0.02), while there was a lack of correlation between post-micturition dribble and detrusor after-contraction (p=0.287). Conclusions So far, different explanations have been suggested for detrusor after-contraction, such as an expression of detrusor overactivity or of post-micturition dribble(1,3). The latest ICS standardisation does not even mention this entity. In the few studies in the Literature a prevalence of detrusor after-contraction considerably higher than the findings of the present study is reported (56% vs 17%) (3). A possible difference in the study populations or a not homogeneous interpretation of detrusor after-contraction, due to the lack of standardisation, could explain this divergence.

In our study a very high prevalence of overactive bladder and detrusor overactivity was found among pts with detrusor after-contraction (76% and 70% respectively). On the other hand, there was only a very low prevalence of post-micturition dribble among pts with detrusor after-contraction (less than 27%). These findings confirm the few data of the Literature (3) and, if confirmed by furher prospective studies, they could lead to consider detrusor after-contraction a sign of detrusor overactivity.

References 1. The after-contraction: a true detrusor contraction or a late dyssynergic urethral sphincter contraction? Br J Urol Int 85 (3): 246-248, 2000. 2. The after-contraction in paediatric urodynamics. Br J Urol 78: 780-782, 1996. 3. Prevalence and significance of detrusor after-contraction. Urodinamica 10 (2): 112-113, 2000. 68 Hvistendahl G M1, Frøkiær J2, Nielsen S3, Djurhuus J C 1 1. Institute of Experimental Clinical Research, University of Aarhus, 2. The Water and Salt Research Center, Institute of Experimental Clinical Research/University of Aarhus, 3. The Water and Salt Center, Institute of Anatomy, University of Aarhus THE DIURNAL RHYTHM OF URINE OUTPUT AND AVP SECRETION IN ELDERLY NOCTURNAL POLYURICS, ELDERLY AND YOUNG CONTROLS. Aims of Study An age-associated defect in AVP secretion during night time has been documented and may explain the increased nocturnal diuresis experienced by the elderly (1) although others have shown a disturbed circadian rhythm in AVP secretion independent of the level of nocturnal urine output (2). Generally elderly women seem to have lower values of AVP than men irrespective of nocturnal voiding (1;3). This study attempts to enlighten the age-related changes in the diurnal AVP secretion and a possible association to changes in diurnal urine output. Methods Elderly and young healthy volunteers were included in the study. Exclusion criteria were anamnestically LUTS with the exception of nocturia, any clinically significant disease, concomitant medication except oral contraceptives, abnormal uroflowmetry including significant residual urine, haematuria, leucocyturia, bacturia, abnormal blood chemistry, excessive fluid intake and an abnormal ECG. The participants were admitted to the hospital for 24 hours. From two days prior to hospitalisation and during the hospital stay the amount and type of fluid intake were standardized. During the hospital stay a diary was kept to register time and volume of fluid intake and voiding episodes. The participants were asked to empty their bladder at least every 3 hours from 8 a.m. to 11 p.m. (daytime) in a separate bottle for each 3 hour period. The nighttime (11 p.m. to 8 a.m.) was represented by only one collection comprising any voiding during the night and the first morning void at 8 a.m. From the individual urine samples urine volume (Uvol) was measured. Samples for plasma AVP analysis were obtained at predetermined hours. Repeated measurement analysis, one way ANOVA and t-tests were used when appropriate. Results were considered significant when p<0.05.

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Results A total of 34 elderly (11 , 23 ) and 23 young (12 , 11 ) healthy volunteers were included. Post-investigation the group of elderly participants was sub-grouped according to the nocturnal urine output in a group of elderly nocturnal polyurics (> 33% urine excretion during nighttime) (N=14, mean age 71.0±1.6 years) and a group of elderly controls (N=20, mean age 68.9±0.89 years). The group of young participants served as a young control group (N=23, mean age 27.1±0.65 years). In the control groups there was a significant diurnal variation in AVP secretion (ptime<0.001) but in the elderly nocturnal polyurics this circadian variation was missing (p=0.172) (fig.1).

Sampling time

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Fig. 1. The diurnal plasma AVP concentration (ENP=elderly nocturnal polyurics, EC=elderly controls, YC=young controls). In general men had higher nocturnal levels of plasma AVP than women. Likewise the daytime levels were higher in the elderly nocturnal polyuric men and in the young control men than in the respective women. Only in the group of young controls there was a significant difference in the diurnal AVP secretion between sexes (p=0.01). The mean baseline day/night urine excretion ratio in the elderly nocturnal polyurics was <1 (0.81±0.088) and significantly lower than the corresponding values in the control groups. The young controls had a mean day/night urine excretion ratio of 2.36±0.16, almost three times the value in elderly nocturnal polyurics, whereas the elderly controls had a mean day/night urine excretion ratio of approximately twice the value of the nocturnal polyurics (1.89±0.14). There was no within group gender difference in the day/night urine excretion ratio and we found no correlation between nocturnal plasma AVP and nocturnal urine output. Conclusions Young women have low nocturnal plasma AVP levels compared to young men in spite of comparable levels of nocturnal urine output. Elderly women had plasma AVP levels close to the levels measured in the elderly nocturnal polyuric women. A diminished diurnal variation in AVP secretion in young women have been reported elsewhere and similar results have been presented in elderly women indicating that women in general have increased sensitivity and/or affinity of AVP at kidney receptor level. Other factors such as oestrogen status may play an important role in the maintenance of water homeostasis in young women. References

1. Asplund R, Aberg H. Diurnal variation in the levels of antidiuretic hormone in the elderly. J Intern Med 1991; 229(2):131-134.

2. Matthiesen TB, Rittig S, Norgaard JP, Pedersen EB, Djurhuus JC. Nocturnal polyuria and natriuresis in male patients with nocturia and lower urinary tract symptoms. J Urol 1996; 156(4):1292-1299.

3. Olsson T, Viitanen M, Hagg E, Asplund K, Grankvist K, Eriksson S et al. Hormones in 'young' and 'old' elderly: pituitary-thyroid and pituitary- adrenal axes. Gerontology 1989; 35(2-3):144-152.

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69 Morris A R1, Westbrook J I2, Moore K H1 1. Pelvic Floor Unit, St George Hospital, 2. Department of Health Informatics, University of New South Wales IDIOPATHIC DETRUSOR OVERACTIVITY IN WOMEN – A 5-10 YEAR LONGITUDINAL STUDY OF OUTCOMES Aims of Study To date, there have been no published data about either the long-term response to therapy for urodynamically proven detrusor overactivity (DO), nor about the natural history of the disease. We conducted a retrospective cohort study of patients with DO 5-10years after first clinic attendance. We aimed to: 1) determine whether patients with the phasic and non-compliant form of the condition differed substantially with respect to clinical characteristics and outcomes. 2) examine clinical outcomes at (a)the last clinic visit and (b)5-10years after the date of the first visit. 3) describe the natural history of the disease in the 5-10 year period from initial visit. Methods A consecutive series of patients who ha urodynamically proven DO and initially attended a tertiary urogynaecology clinic between 1992-1997 were identified. All urodynamic tracings were re-examined. Patients with co-existent lower urinary tract dysfunction were excluded (Figure 1). Figure 1. Study sample

Patients with sole diagnosis of DO N=132

↓ Patients dead N=19 (14%)

Questionnaires administered N=113

↓ Participants

N=76 (67%)

Non-Participants N=37 (33%)

No outcome data N=5(4%) ←↓

Outcome data N=71 (63%)

Demographic parameters, duration/nature of presenting symptoms, past medical history/treatments, family history, data from the initial 24hour frequency/volume chart & cystometry report were abstracted. Outcomes were defined at two time points as follows: 1) Outcome at last clinic visit: At each visit the treating physician recorded the percentage change in symptoms from baseline (ie at time of initial visit). The outcome status as recorded at subjects’ final visit was abstracted and categorised for analysis as per Table1. 2) Outcome 5-10years post initial clinic visit: A followup questionnaire enquiring about subjects’ current LUT symptoms & perceived course and outcome of their disease was administered. Outcome was determined by respondents’ views about how effective treatments had been in reducing symptoms. Information about potential confounders, eg pelvic surgery, recent menopause, was sought. Short forms of the Incontinence Impact Questionnaire (IIQ) and Urogenital Distress Inventory (UDI) were incorporated into the survey. Each questionnaire was accompanied by a reply-paid envelope. A second questionnaire was mailed if the first wasn’t returned.

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Table 1. Outcome Categories

Results The median age at symptom onset was 50 years (range 32-69) and at presentation was 60 years (40-74). Patients received a median of 2 (1-4) treatments over 8 (3-24) months. Phasic vs non-compliant DO: Onset of symptoms was similar [52 years (32-70) vs 47 (32-67), MW-U (MW-U),P=0.56]. Bedwetting was more frequent in phasic DO [16/70 (23%) vs 3/51 (6%), χ2=6.42, p=0.01] vs non-compliant DO. This difference persisted at 5-10 years [8/40 (20%) vs 1/36 (3%), x2=5,38, p=0.02]. No association was found between nocturnal enuresis in childhood and cystometric sub-type (χ2=0.14,P=0.71). Response to treatment was similar at last clinic visit (χ2=0.04,p=0.85) and at 5-10 years followup (χ2=0.09, p=0.75). As underlying cystometric sub-diagnosis did not influence outcome, both sub-types were combined for further analyses. Outcome at last clinic review: As defined, 50-100% treatment response occurred in 49% of women (table 2). Treatment responders and non-responders first experienced symptoms at similar ages [respectively 53 years(30-68) vs 48 years( 33-70) , MW-U,p=0.97] and had disease of a similar duration [6.4 years (2.7 – 12.7) vs 5.7 years (2.1 – 10.8),MW-U=0.07]. Those who bed-wet in childhood (χ2=4.28 p=0.04) and day-wet past age 5 (χ2=5.57 p=0.02) were significantly more likely to be refractory to treatment. Of those having undergone hysterectomy, 56%(23/41) responded to therapy compared to 46%(42/91) of those who had not had a hysterectomy (χ2 =1.11,p=0.29). Table 2. Outcome by time and diagnostic sub-type

Last clinic review (N=132) Questionnaire (N=71) Responded to Rx Not responded Responded to Rx Not responded 65 (49%) 67 (51%) 25 (35%) 46 (65%) Phasic 36 (55%) NCDO 29 (45%)

Phasic 39 (58%) NCDO 28 (42%)

Phasic N=14 (56%) NCDO N=11 (44%)

Phasic N=24 (52%) NCDO N=22 (48%)

Outcome at 5-10 years: The participation rate was 67%. Participants and non-participants were not significantly different for any baseline variable. Satisfactory response to treatment was reported by 25/71 (35%) women. Women that responded reported symptoms for less time than those who did not [10 years (7-16) vs 15 (10-18),MW-U,p=0.049.] Non-responders described urgency (p=0.02) and urge incontinence (p=0.001) more often at first consultation. No difference was noted in response amongst 14 (20%) patients who described recurrent cystitis (χ2=0.39,p=0.53). Figure2. Reported course of detrusor overactivity (N=74)

Status at last review (Improvement from baseline)

Category for analysis Status at 5-10years (questionnaire)

>=75% “Cured” 50-74% ‘Responded’ “Helped a lot” 10-49% “Helped a little” 0-10% ‘Not responded’ “No help”

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Conclusions Phasic and non-compliant DO are similar as regards symptoms and prognosis. As per figure 2, only 16% of women reported improvement in symptoms over 5-10years. Childhood bedwetting and day-wetting are associated with poor outcome. Complete resolution of DO is unlikely (4%). 70 Blackwell A L1, Moore K H1 1. Pelvic Floor Unit, St George Hospital, Sydney DOES DETRUSOR OVERACTIVITY EVER CEASE? REPEAT URODYNAMIC TESTING AT 1 TO 9 YEARS. Aims of Study Little is known about the natural history or progression of pure idiopathic detrusor overactivity (IDO). Few studies of repeat urodynamic tests have been performed in IDO. We do not know whether the condition ever spontaneously regresses to normal, nor what percentage of cases become stable, after therapy, in the longterm. Previous authors have considered the issue of test-retest reliability in normal controls when urodynamic studies (UDS) were performed on the same day (1) or up to two months later (2). Only one longterm study, published in the pre-oxybutinin era, assessed the persistence of urodynamically proven IDO in 37 women (3). They found the maximum detrusor filling pressure remained within 15 cm H2O of the baseline study in 73%. Some subjects had been given drug treatment in the interim but they were not characterized separately. The authors did not reveal whether IDO ever spontaneously regressed. The aim of this study is to investigate the natural history of IDO, over a maximum of 10years. That is whether IDO ever regresses without pharmacotherapy, and what percentage become stable in the longterm after a period of pharmacotherapy. Also to establish whether phasic and non-compliant forms of IDO remain consistent over time or whether these forms of the condition may be interchangeable over time. Methods A retrospective study of all women with urodynamically proven pure IDO who attended our Unit between it’s opening in July1992 and December2001, and who had had at least two urodynamic studies performed. Any drug treatment was noted. In our unit, patients with IDO were uniformly given bladder training instructions +/- oxybutynin or tolteridine. Patients with a diagnosis of pure IDO who failed to become continent with anticholinergic therapy sometimes underwent repeat urodynamics on therapy to exclude coexistent genuine stress incontinence that may not have been evident at the first test (dependent upon symptomatology). Subjects were identified from the urodynamic results database. Notes of all those with pure IDO, sensory urgency(SU) (ie. first desire less than 150mls and maximum capacity less than 400mls with a stable bladder) or normal studies were hand searched to see if they had had more than one investigation including a diagnosis of pure IDO at one point. Original urodynamic traces were uniformly scrutinized. Results were grouped according to the trends demonstrated by Figure1. Results The search has so far identified 42 women with at least one diagnosis of pure IDO and at least two UDS (range 2-6). Median age at first UDS was 54yrs (IQR 41–68.5yrs, range 22–83). Median time between the first and second UDS was 26.5months (IQR 5–48months, range 2–173). Analysis is ongoing, results accrued to date are described. In summary, 29 of 42 subjects (69%) who underwent repeat UDS had persistent IDO regardless of treatment. All of those receiving no treatment, eg. on placebo arm of controlled trial, remained unstable. When IDO was treated with interim anticholinergic therapy it was seen to persist at the second study in 24 of 28 cases (85.7%)(upper section of Figure 1).

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Figure1. Longterm patterns of detrusor overactivity. * t = median time interval of UDS in months.

There were two cases of spontaneous regression of IDO in which SU was found on the second UDS (ambulatory studies were not generally available). In another four cases (total 6/35=17.1%), where anticholinergic therapy had been prescribed, IDO was no longer apparent at the subsequent UDS. Phasic IDO remained so in 26% of cases. Non-compliant IDO also did not change in 10% of cases (data not shown). However, in 28% cases phasic IDO shown on the first UDS was found to be non-compliant on the second UDS. Similarly non-compliant IDO became phasic on the second UDS in 50% of cases. Conclusions To our knowledge this study describes the first representation of the longterm pathophysiology of IDO in patients who have been treated with modern anticholinergic therapy. It would appear that the majority of patients with IDO have a persistent unstable detrusor at a range of 1-9years despite conventional therapy. This has not previously been demonstrated. The interchangeability of non-compliant and phasic IDO was also a surprising finding. References

1. Short-Term Reproducibility of Cystometry and Pressure-Flow Micturition Studies in Healthy Women. IntJUrogyn 2001; 12: Suppl 3, 98.

2. Urodynamic investigations and their reproducibility in healthy postmenopausal women. ScanJUrolNephrol 1998; Suppl114: 42–47.

3. A long-term Study of the Persistence of the Urodynamic Characteristics of the Unstable Bladder. BrJU 1981; 53: 310–314.

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71 Lutgendorf S1, Rothrock N1, Hoffmann A1, Zimmerman B1, Latini J1, Kreder K1 1. University of Iowa AUTONOMIC RESPONSE TO STRESS IN INTERSTITIAL CYSTITIS Aims of Study The hypothesis has been advanced that interstitial cystitis (IC) patients have greater sympathetic tone and greater reactivity to stress than healthy individuals. Sixty percent of IC patients report symptom exacerbation by stress [1]. The stress response involves physiological adaptation to stimuli perceived as physically or emotionally threatening [2] with activation of the sympathetic nervous system, hypothalamic-pituitary-adrenal axis, immune system and various other physiologic and psychological effects. Findings consistent with the sympathetic effects on the inflammatory processes in IC patients have been documented. Increased symptoms of pain and urgency with voiding were evoked by an acute mental stressor in IC patients but not controls [3]. This study examines effects of a laboratory mental stress challenge on blood pressure and heart rate in IC patients and in healthy controls. Methods Fourteen female IC patients and fourteen age-matched female controls participated in a laboratory session, including a 60-minute baseline, 25-minutes of mental stress tasks, and 75-minutes of recovery. The mental stress challenge involved a 5-minute videotaped speech task, a 14-minute computerized Stroop word color test [4] and 6-minutes of mental arithmetic performed aloud. Systolic (SBP) and diastolic (DBP) blood pressure and heart rate (HR) were measured at regular intervals (every 2 minutes) beginning 15-minutes before the stressor, during the stress challenge, and until 100 minutes following the onset of the stressor. Level of chronic stress, symptom severity and pain at voiding were also assessed during the session (NIDDK Interstitial Cystitis Data Base symptom questionnaire) [5]. Results The mean age of participants was 49 years (range, 32-66). There was no difference in average reports of chronic stress during the week prior to the study session in patients or controls. In both groups, the laboratory stressor was effective in eliciting a stress response characterized by autonomic arousal, as measured by increased SBP (p<0.001), DBP and HR. Both groups perceived the task as equally stressful. HR of IC patients at baseline (82.02 beats per minute) was significantly higher than that of controls (63.31 bpm; p=0.0001). IC patients had significantly elevated HR at each time-point measured as compared with controls (all p values <0.0001) (Figure 1), with a relatively constant average mean difference between groups of 19.5 bpm (S.D. 4.0; main effect for group p < 0.0001). This suggests that although there was a consistent elevation in HR among IC patients, there was not a difference in HR reactivity to stress between groups. Although both SBP and DBP were consistently elevated in patients as compared to controls, these elevations were not significant (p=0.12) (Figure 2), and there was not a difference in blood pressure reactivity to stress between groups. Assessments of HR change in conjunction with pain over time indicated that in IC patients: for a 1-unit increase in pain score, there was a 0.9 unit increase in HR. This relationship was not evident in controls. Pain level did not change in controls. Conclusions Female IC patients have elevated HR at baseline and throughout a laboratory mental stress challenge compared to healthy age-matched women. Differences in HR and blood pressure reactivity between the two groups were not evident. This physiologic evidence adds support to the hypothesis that patients with IC have greater sympathetic tone at baseline than healthy women but do not have greater sympathetic reactivity to stress. These results are consistent with reports of stress related exacerbation of clinical symptoms and parameters in other neuroinflammatory conditions (rheumatoid arthritis, psoriasis, irritable bowel disease). Further evaluation of the physiologic mechanisms underlying stress related Interstitial Cystitis symptom exacerbation is needed.

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Figure 1: Heart rate (HR) in patients with interstitial cystitis and controls with time. Stress challenge occurred between minutes 0 and +25 (arrow). HR was significantly greater in patients than in controls at baseline and at all time points (all p values < 0.0001).

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Figure 2: Systolic blood pressure (SBP) in patients with interstitial cystitis and controls with time. SBP was consistently elevated in patients compared to controls at all time points. These elevations were not significant (p=0.12). References 1. Koziol JA, Clark DC, Gittes RF et al. The natural history of interstitial cystitis: a survey of 374 patients. J Urol 1993;149:465. 2. Chrousos GP and Gold PW. The concepts of stress and stress system disorders. Overview of physical and behavioral homeostasis. JAMA 1992;267:1244. 3. Stress and symptomatology in patients with interstitial cystitis: a laboratory stress model. J Urol 2000;164:1265. 4. Dyer FN. The Stroop phenomenon and its use in the study of perceptual, cognitive and response processes. Mem Cognit 1973;1:106-120. 5. Simon LJ, Landis JR, Erikson DR, et al. The Interstitial Cystitis Data Base Study: concepts and preliminary baseline descriptive statistics. Urology 1997;49(5A suppl):64-75.

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72 van Ophoven A1, Rossbach G1, Oberpenning F1, Hertle L1 1. University of Muenster HYPERBARIC OXYGEN FOR TREATMENT OF INTERSTITIAL CYSTITIS: RESULTS OF A PILOT STUDY Aims of Study Hyperbaric oxygen (HBO) treatment has already been used extensively and successfully for the treatment of chronic radiation cystitis, a condition that corresponds closely to interstitial cystitis regarding symptoms, histological characteristics and therapeutic approaches. In late stage disease, acute and chronic ischemia of the bladder wall occurs in both the IC and radiation affected bladder. Symptoms commonly associated with both bladder diseases include urinary frequency, urgency, urinary urge incontinence and pelvic pain. Many patients suffering from either radiation cystitis or interstitial cystitis develop a significant reduction in bladder capacity secondary to fibrosis of the bladder wall. Several investigators have studied the use of HBO in patients with radiation cystitis and reported remarkable response rates regarding the reduction of pelvic pain and irritative voiding symptoms, particularly urgency. The encouraging results of HBO treatment for radiation cystitis in addition to the correspondence of histological and clinical characteristics between both bladder diseases led us to conduct a prospective pilot study of HBO in IC patients. Technically the delivery of hyperbaric oxygen occurs when the patient rests the whole body and breathes 100% oxygen in a treatment chamber which is pressurized to higher than sea level, for example greater than 1 atmospheres absolute (ata.). Pressurization between 1.4 and 3.0 ata. while the patient inhales oxygen meets the Undersea and Hyperbaric Medicine Society definition of hyperbaric oxygen treatment. Methods The study comprised 1 male and 5 female patients who all met the symptom criteria of the National Institute of Diabetes, Digestive and Kidney Diseases for IC. All patients underwent 30 sessions of 100% oxygen inhalation via a facial mask for 90 minutes in a multiplace hyperbaric chamber. The efficacy of HBO treatment was assessed at the end of treatment and after a followup interval of 1, 3 and 9 months. The measures of efficacy were change in pain and urgency (100 mm. visual analog scales) and alteration in the patient’s assessment of overall change in his wellbeing (patient global assessment form). Further measures of efficacy addressed changes in daytime frequency, nocturia, functional bladder capacity (48-hour voiding log) and reduction of urinary urge incontinence (pad count/ voiding diary). Evaluation of symptom severity regarding pain and voiding problems was done using a validated, self-administered index (O´Leary et al.). This index comprises 8 questions assessing major pain and voiding symptoms. The maximum index score of 35 reflects maximum symptom and problem severity and the lowest possible score is 0 (i.e. no symptoms). Finally, patients were requested to rate their satisfaction with the therapeutic outcome. Results 4 patients rated the therapeutic result as either excellent or good and assessed their wellbeing after HBO treatment as improved. 2 patients showed only short-term amelioration of some of their symptoms and were thus not satisfied with their therapeutic result at followup. Baseline functional bladder capacity ranged from 37-161 ml. in the responder group, and HBO treatment resulted in a bladder capacity ranging from 160-211 ml. in these patients, i.e. a maximum increase of 430%. In the group of responding patients the 24-hour voiding frequency decreased from 15-27 (range) to 6-8 voids per day. Nocturia decreased from 2-8 to 0-2 voids per night after treatment. Pain and urgency improved remarkably in these 4 patients (pain scale improvement from 20-97 mm. pre-HBO to 3-30 mm. post-HBO; urgency scale improvement from 53-92 mm. to 0-40 mm. respectively). The symptom and pain index score decreased correspondingly from 23-35 points pre-HBO to 1-17 points post-HBO. At baseline 3 patients presented with moderate and 1 patient with severe urge incontinence. All 4 patients experienced sustained and full relief from this condition. No major adverse events were observed in all 6 patients. All 4 responding patients recommended HBO treatment for IC. Conclusions HBO seems to be a safe and promising therapeutic option for IC patients. Treatment was well tolerated and resulted in a decrease of pelvic pain and urgency, improvement of voiding patterns and increase of functional bladder capacity. This pilot study served as proof-of principle and a controlled randomized study

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is currently initiated to add HBO treatment to the contemporary armamentarium of interstitial cystitis therapy. 73 Lazzeri M1, Beneforeti P1, Turini D1, Spinelli M2, Malaguti S2, Giardiello G3 1. Department of Urology - S. Chiara Hospital, 2. Spinal Unit - Magenta (Milan), 3. Medtronic - Italy CONTINUOUS INTRAVESICAL INFUSION OF RESINIFERATOXIN BY IN SITU DRUG DELIVERY SYSTEM TO TREAT INTERSTITIAL CYSTITIS: A PILOT STUDY. Aims of Study Interstitial cystitis (IC), a syndrome characterized by motor and sensory dysfunction of the lower urinary tract, represents a diagnostic and therapeutic challenge even to highly skilled physicians. Intravesical conservative vanilloid pharmacotherapy remains one of the mainstays in the treatment of IC. The aim of this study is to investigate the technical feasibility and the clinical efficacy of a continuous intravesical instillation of RTX by in situ drug delivery system in patients with IC. Methods The study involved 6 female patients (mean age 46.5 years), who presented a diagnosis of IC according to the Interstitial Cystitis Data Base (ICDB) study eligibility criteria. All patients reported frequency ( 7), nocturia ( 2) and urgency, and symptoms of pelvic pain for at least 6 months. The pre-treatment (PT) voiding pattern and a pain score (VAS scale) were recorded. Patients were evaluated after 30 days from the end of infusion (primary end point - PEP) and after three months (secondary end point - SEP). For each patient we considered the mean value of three consecutive determinations. A continuos intravesical infusion of RTX was performed by MiniMedR 407C Infusion Pump (MiniMedR Sylmar, CA – USA). The pump reservoir was filled with 3 ml of a saline solution contained 10nM RTX. The flow rate was 25�l/h (0.6 ml/die) x 10 days. Results At PEP frequency reduced from 11.8 ± 0.82 to 7.6 ± 0.65 (p < 0.01) and nocturia from 3.2 ± 0.34 to 1.43 ± 0.11 (p < 0.01). A highly significant reduction of pain score was observed at PEP; it decreased to 2.76 ± 0.34 from 7.1 ± 0.55 (p < 0. 01). The pain score remained significantly lower at SEP (3,25 ± 0.6 p < 0.05). Nocturia was also statistically reduced at SEP (1,82 ± 0.65) as well as frequency (7,8 ± 1.52). At SEP 1 patient reported the complete disappearance of symptoms, the other 5 claimed an improvement of their quality of life, even if their symptoms had not completely disappeared. No side effects were reported during the infusion as well as after the removal of the catheter. Conclusions The present study demonstrates that the continuous intravesical instillation of RTX by in situ drug delivery system is a feasible, easy, safe and fast procedure and seems to support the efficacy of RTX in the treatment of IC patients.We know very well that sharp boundaries between protective and pathological role of bladder capsaicin-sensitive sensory nerves can not be easily drawn with present knowledge, but our hypothesis remains attractive. However further studies are necessary and mandatory to confirm our results and to define the exact action mechanism of continuous infusion of RTX, the dosage and the treatment schedule

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74 Cardozo L1, Prescott K2, Serdarevic D2, Skillern L2 1. Urogynaecology Dept, Kings College Hospital, 2. Pfizer, Sandwich CAN MEDICATION PROLONG WARNING TIME? Aims of Study Symptoms of an overactive bladder (OAB) syndrome are very common and can have a serious negative impact on quality of life. For individuals with OAB, urgency and the associated ‘warning time’ (the time from the first sensation of urgency to micturition) are important. The longer the warning time, the greater the chance of avoiding the social embarrassment of urinary incontinence. Furthermore, recognition of the concept of warning time is important if patients wish to achieve continence (1). However, the application of warning time as an outcome measure in clinical trials evaluating antimuscarinics for the treatment of OAB is not routine and is only rarely mentioned in the literature (2). The objectives of this proof-of-concept study were to assess the potential of anti-muscarinic medication (darifenacin) to prolong warning time and to evaluate the potential utility of warning time as a novel method of assessing urgency. Methods This was a randomised, double-blind, placebo-controlled, parallel-group study with a 2-week, medication-free run-in period. Individuals who had the symptom of urgency for at least 6 months prior to the study, and the same symptom occurring a minimum of 4 times/day during the run-in period, were randomised to 2 weeks’ treatment with darifenacin 30 mg once daily or placebo. Warning time was defined as the time from first sensation of urgency to voiding. Average warning time (the mean of at most 3 warning times recorded at each clinic visit) was used as the primary endpoint. Warning time and the levels of sensation were recorded in ambulatory individuals with the aid of small portable electronic event recorders. The primary analysis was based on the change from baseline to end of treatment (Week 2) in average warning time. The Wilcoxon rank-sum test was used to test for differences between the two treatment groups (3). A secondary endpoint (response defined by 30% improvement in average warning time) was analysed using a logistic regression model (adjusting for baseline warning time, age and gender). Results Seventy-two individuals (mean age 54 years) entered the study and 67 of them (those with both baseline and post-baseline warning times) were included in the primary efficacy analysis, 32 having received darifenacin, and 35 a matching placebo. Change in average warning time from baseline to Week 2 was 4.3 min longer in the darifenacin group than in the placebo group, and the difference was statistically significant (95% CI 1.2, 7.4; p=0.003). The number of individuals who showed at least a 30% improvement in average warning time was significantly higher in the darifenacin group compared with the placebo group (47% compared to 20%, p=0.009). The odds of an individual in the darifenacin group responding with an increase of at least 30% in warning time were calculated to be 5.6 times (95% CI 1.5, 20.1) higher than in the placebo group.

Figure 1: Box-whisker plots of average warning times at baseline and Week 2

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Warning time was assessed using the mean of at most three warning times. Some individuals exhibited a large variation in warning times, indicative of the inherent difficulty in measuring this parameter, and suggesting that other summary measures may be more appropriate. Possible alternate measures could be the median warning time, which would lessen the influence of extreme values, or the minimum warning time which, it could be argued, is the measure of most relevance to an individual. Reanalysis of this study using these alternate endpoints was consistent with the initial analysis in demonstrating that darifenacin produced a statistically significant change in warning time compared with placebo. Using the minimum warning time, the difference in the change from baseline to Week 2 between the darifenacin and placebo groups was 1.9 min (95% CI 0.2, 4.2; p=0.017). Conclusions In this study, average warning time proved to be an effective and novel endpoint for the assessment of urgency. This study is the first to provide an objective demonstration of a significant, positive effect of an antimuscarinic on warning time indicating that warning time could be employed to assess the efficacy of treatments for urgency or OAB. References 1. Urinary continence/incontinence. Recognizing warning time: a critical step toward continence. Geriatr Nurs 1980; 1: 254-5. 2. Measuring the sensations of urge and bladder filling during cystometry in urge incontinence and the effects of neuromodulation. Neurourol Urodynam 2003; 22: 7-16. 3. Applied Nonparametric Statistical Methods. London, Chapman and Hall, 1989. 75 Madersbacher H1, Berner L1, Struhal G1, Eisenmenger M1, Neumann M1 1. Austrian Continence Society EVALUATION OF OAB TREATMENT AND PATIENT SATISFACTION REFLECTING ‘REAL LIFE CONDITIONS’ IN UROLOGICAL OFFICES IN AUSTRIA Aims of Study There is a broad basis of large randomised trials on the usage of antimuscarinics, such as tolterodine, for the treatment of patients with OAB symptoms. The day-to-day setting in a normal office can usually not reflect the stringent inclusion criteria of such studies. In this investigation we aimed to assess the outcome of treatment of a broad range of patients with OAB symptoms typical for an office-based setting in order to find evidence that the results from controlled clinical trials are ‘reproduceable’ in the normal life situation.

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Methods 406 patients with OAB were documented in an open-label evaluation by 45 urologists (36 office based, 9 outpatient clinics) at baseline and in median 4 and 9 weeks after initiation of treatment with Detrusitol IR (2 x 2 mg). To avoid a possible bladder-training effect voiding diaries were not compulsary. The outcome measurement was based on the change of the perception of bladder condition and the assessment of effect of the treatment on restriction of daily life, nocturnal disturbances and treatment satisfaction. Included were patients with OAB symptoms eligible for antimuscarinic treatment. 30 % of the patients were recruited prospectively, 70 % included retrospectively, 39 % had experienced other drug treatments for OAB previously, 61 % were treatment-naïve. There were no statistically significant differences of baseline characteristics between these groups. The evaluated outcome variables were change of patient perception of bladder condition assessed with a validated 6-point bladder condition scale1), patient assessment of change of restriction of daily life, nocturnal disturbance and treatment satisfaction, complemented by an assessment of the physicians on treatment success. Tolerance was evaluated by assessing the severity of dry mouth. Results Of 406 patients included 390 completed the 1st assessment after 4 weeks, 335 the 2nd after 9 weeks and 299 the final assessment after 11 weeks (values: median). The majority of patients were female (66 %) and the median age was 67 years. All outcome variables showed highly significant improvements. The bladder condition (rated from ‘many severe problems’ to ‘no bladder problems’) was perceived improved by 85 % / 90 % of the patients at the 1st /2nd assessment. The subgroup of pretreated patients showed a slightly but statistically not significant lower improvement of their bladder condition with 81 % and 87 % respectively. Regarding restriction of daily life 86 % of patient judged their life at baseline as very restricted or restricted by their bladder problems. At the 2nd assessment 82 % reported an improvement resulting in a drastic shift of 77 % of the patients judging no or minor restrictions of their daily life. At baseline, an unexpected high share of 68 % of the patients reported that they have nocturia 2 or more times per night. This share improved to just 19 % after the 2nd assessment. The treatment was well tolerated: 55 % reported no and 37% just minimal dry mouth, 6 % severe and only 1,5 % experienced very severe dry mouth problems and just one patient terminated treatment because of side effects. The rate of dry mouth compared favourable to the rate experienced at prior drug treatment with 62 % showing very severe or severe dry mouth. Regarding overall patient satisfaction 79 % / 88 % at 1st/2nd assessment of the patients were very satisfied or satisfied with their OAB treatment. At final evaluation of the treatment outcome 86 % of patients assessed the therapy success as very good or good and 89 % reported an amelioration of their quality of living. Not surprisingly also the final physician assessment of the treatment effectiveness was evaluated with 44 % as very good and 43 % as good. The comparison of the results of the prospective and the retrospective group showed an inconsistent picture. In the variables change of bladder condition, restriction of every day life and final patient assessment of treatment success the results for the prospective group were slightly better, whereas for nocturnal disturbance and the rate of dry mouth the outcome was marginally better for the retrospective group, all other variables showed no significant difference. Overall, these differences did not change the total picture of the results. Conclusions The results on clinical effectiveness in a true reflection of the real-world situation in Austria showed a very favourable assessment of patients and physicians of the treatment of OAB symptoms with tolterodine in a representative number of patients. All outcome variables improved statistically highly significant compared to baseline. From this assessment we conclude that the results from international randomised trials can be extrapolated to the every-day practice. With tolterodine the clinical effectiveness in the treatment of OAB intended is achieved in a high majority of the patients according to assessments by patients and physicians. References 1) Coyne KS, Matza LS. Validation of the perception of bladder condition measure in overactive bladder. Poster at ISPOR (Int. Soc. for Pharmacoeconomics and Outcome research) 7th Annual Meeting May 19-22, 2002, Arlington.

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76 Bosch R1, Groen J1 1. Erasmus Medical Center CHRONIC SACRAL (S3) NERVE STIMULATION: THE EFFECTS ON NOCTURIA AND NOCTURNAL BLADDER CAPACITY AND CORRELATES WITH SUPINE URODYNAMICS IN WOMEN WITH REFRACTORY URGE URINARY INCONTINENCE Aims of Study Nocturia can have a significant impact on sleep patterns and quality of life.The aim of this study was to evaluate the effects of chronic sacral (S3) nerve stimulation on nocturia (nocturnal voiding frequency [NVF] > 1) in women with refractory urge urinary incontinence. It is assumed that electrical stimulation of sacral somatic nerve afferents carried by the pudendal nerve can induce detrusor inhibition. The S3 spinal nerve carries pudendal nerve afferents and can be used for electrical stimulation in the treatment of detrusor overactivity (DOA). The efficacy of this treatment has been shown in pivotal trials that were conducted in patients with urge incontinence [J Urol 162:352, 1999] and urge-frequency [J Urol 163: 1849, 2000]. However, in these trials, the possible effect of SNS on nocturia and the mechanism responsible for the effect have not been studied. Methods Patients who reacted favorably to percutaneous nerve evaluation (PNE) with a temporary test electrode received a permanent implant: an S3 foramen electrode connected to a pulse generator (Medtronic Interstim). A favorable response is defined as a more than 50% decrease in leaks and pad use. PNE was performed in 114 women with urge urinary incontinence. 54 women responded to the PNE and were implanted. Of these, 26 (50%) had a baseline NVF>1, and a minimum follow-up of 6 months. The stimulation amplitude had been adjusted to achieve an optimal symptomatic result. Filling cystometries, in the supine and in the standing position, and pressure-flow studies have been performed before the implant and at 6 months follow-up with the pulse-generator in the on-mode. Follow-up tests also included bladder diaries (3 to 6 monthly). The nocturnal urine volume derived from the diaries was divided by the maximal cystometric capacity (MCC) during supine filling to calculate the predicted nocturnal voiding frequency (NVFpred). At baseline and after 6 months of follow-up we determined the correlation coefficient between the predicted and the actual nocturnal voiding frequency (NVFact). The nocturnal bladder capacity index (NBCi = NVFact – NVFpred) was calculated at baseline and at 6 months. A higher value of NBCi indicates diminished nocturnal bladder capacity or more severe sensory urgency. Values are expressed as means±SEM. Results Of the 26 patients (age:47±2 yrs), one was lost to follow-up before the 6 month urodynamic study could be performed and one patient refused urodynamics. The average follow-up of the implanted patients with nocturia was 65 (range:6-120) months. At baseline, 2 women did not have detrusor overactivity (DOA), 7 had DOA during filling cystometry in the standing position only, whereas 17 had DOA in the supine and standing position. Furthermore, 4 women had polyuria; one of these and 3 others had nocturnal polyuria. The NVFact and NVFpred at baseline were 2.9±0.4 and 1.7±0.3, respectively.There was no correlation between NVFpred and NVFact:: r = 0.005 (p=0.981) . At 6 months follow-up a > 50% improvement in the number of incontinence pads and the number of leaks, was demonstrated in 20 (74%) women. Furthermore, no patient had polyuria and only 1 had persistent nocturnal polyuria. The correlation between NVFpred (0.5±0.1) and NVFact (1.0±0.2) at 6 months follow-up had increased to r = 0.75 (p=0.0001). The MCC in the supine position increased from 345 (±31) mL at baseline to 414 (±26) mL at 6 months with IPG in the on-mode (p=0.04). The NBCi decreased from 1.4±0.5 at baseline to 0.4±0.1 at 6 months follow-up. Interestingly, the NBCi at baseline did not differ significantly between those who did have supine DOA and those who did not (1.1±0.7 vs 1.3±0.4). The average NVFact decreased from 2.9 (range 1.3-9.7) times at baseline to 1.1 (range 0-3.7) times at latest follow-up (average 65 months).

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The durability of the effect of SNS on NVFact is shown in table 1. Table 1: Durability of effect of SNS on actual nocturnal voiding frequency: Follow-up N Nocturia (years) frequency Pre-implant 26 2.9±0.3 1/2 year 26 1.0±0.2 1 year 24 0.8±0.1 2 years 19 1.2±0.2 3 years 19 1.1±0.2 4 years 17 1.1±0.2 5 years 15 1.1±0.3 Conclusions SNS has a durable effect on nocturnal voiding frequency in women treated for refractory urge urinary incontinence. The data also give insight in the mechanism of action. The lack of correlation between NVFact and NVFpred at baseline indicates that the MCC found during supine filling cystometry is a poor determinant of nocturnal voiding frequency. Furthermore, the NBCi at baseline does not seem to depend on the presence or absence of DOA on supine filling. After 6 months of treatment the NBCi has decreased significantly and the correlation between NVFact and NVFpred has become very good (r=0.754). These findings indicate that a “sensory” effect is more important than a “motor” effect in order to achieve a significant improvement of nocturia in this group of patients. 77 Reid S V1, Parys B T1 1. Rotherham District General Hospital THE RISE AND DEMISE OF THE VESICA PROCEDURE – LESSONS TO BE LEARNT ABOUT BLADDER NECK SUSPENSION Aims of Study The treatment of stress urinary incontinence (SUI) has had many procedures described with the aim of restoring the urethra to a well supported position. The gold standard is considered to be the Burch colposuspension but emphases on minimally invasive procedures and short inpatient stays prompted the development of new techniques one of which was the Vesica percutaneous bladder neck suspension (PBNS). Initially it was hailed as a great success but few long term results have been reported. The aim of this study was to prvide 5 year data on this procedure. Methods A total of 40 women with urodynamically proven SUI underwent Vesica PBNS between 1994 and 1997. From bone anchors drilled into both pubic tubercles a prolene suture was passed retropubically and a z stitch placed to include anterior vaginal wall and endopelvic fascia either side of the bladder neck and urethra. The prolene suture was then tied to the bone anchor over a spacer to achieve correct tension. Results Patients were assessed at 6 months, 12 months and 5 years. One patient was lost to follow up. Initial results were excellent with 85% of women reporting complete dryness at 6 months. However 16% developed wound infections secondary to haematomas in the suprapubic incisions and 10% required a period of intermittent self catheterisation because of incomplete bladder emptying post operatively. By 12 months only 46 % of the women remained dry although most only reported occasional leakage. At five years 69% had recurrence of SUI and more than two thirds (70%) of this group had symptoms severe enough to be offered a further surgical procedure. Two patients developed significant irritative symptoms

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which was caused by erosion of a Vesica suture into the bladder and required surgical removal. One patient developed erosion of suture into the vagina also requiring surgical removal. Conclusions Initial results from this minimally invasive procedure were excellent and despite the lack of long term data the technique very quickly came into widespread use. ‘Wonderful’ new minimally invasive procedures for SUI are still gaining popularity despite scant long term data. Lessons must be learnt from the Vesica experience. 78 Moore K N1 1. University of Alberta A STUDY ASSESSING THE SAFETY, EFFICACY, COMFORT, AND PATIENT SATISFACTION WITH THREE COMMONLY USED PENILE COMPRESSION DEVICES FOR MALE INCONTINENCE AFTER PROSTATECTOMY. Aims of Study After radical prostatectomy (RP) some men experience annoying or continuous incontinence. If pelvic floor muscle exercises are not effective, there are 3 nonsurgical choices: pads, condom drainage, or penile compression devices. To date there have been no published reports on the clinical use of penile compression devices despite their availability for many years in shops and over the internet. In this study we assessed the safety, efficacy, comfort, and patient satisfaction with 3 penile compression devices: the Cunningham Clamp (Bard Urological; Covington, Georgia), C3 (Timms Medical Technologies, White Bear Lake, MN), and U-Tex devices (marketed by Laborie). Outcome measures were: 1) gm of urine lost on 4 hour pad test, 2) Circulatory impedance measured by penile doppler ultrasound (10 cm/s or more safe level) and 3) Patient satisfaction assessed by a patient completed questionnaire. Ethical approval was received from the Health Research Institutional Board. Methods Penile compression devices were tested in random order in a multiple period crossover design using a Latin squares configuration. Eligible men were at least 6 months post RP with no neurological or cognitive impairment (Mini Mental State Exam > 27) and who had not undergone radiotherapy. Subjects were instructed on the use of each device, applying the device only tightly enough to stop leak with a gentle cough and then provided a return demonstration of the use, repeating the instructions aloud. They then underwent a baseline penile doppler ultrasound followed by an ultrasound with each device in place, tested in random order. Devices were applied at a comfortable pressure sufficient to stop urine flow with gentle cough. Right and left systolic velocities and resistance indices of penile blood flow were calculated. A baseline 4 hour pad test was conducted to assess urine loss followed by a 4 hour pad test using each device and questionnaire completion at the same time on subsequent days. Subjects were asked to adhere to the same activity and fluid intake for each of the four measurements. A four hour pad test was chosen as four hours is the maximum length of time we recommended that a penile compression device be worn at any one time. Results 12 men completed the study. Mini mental state exam score was mean 29.6, sd 1.2 (27-30). Mean urine loss at baseline (without device) was 122.8 gm (sd: 130.8) in the 4 hour pad test; mean urine loss was significantly decreased for the three compression devices compared to baseline: U-Tex 53.3 gm (sd:65.7); C3 32.3 gm (sd:24.3); Cunningham 17.1 g (sd:21.3) (Table 1). For all subjects there were some subjective and objective improvements in continence with at least one of the devices tried. Highest satisfaction was noted for the Cunningham clamp and was linked to ease of application, comfort, and efficacy. The U-Tex device was consistently ranked lower than the other two because it was difficult to apply, did not stay on with activity, and did not control urine leakage satisfactorily. None of the three devices had a significant

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impact on the resistive index; the C 3 and U-Tex allowed good distal penile blood flow; the Cunningham clamp significantly lowered distal blood flow velocity (from 12.5 cm/s to 7.3 (left systolic velocity) to 9.5 cm/s (right systolic velocity) even at the loosest setting (see Table 2). Despite its slightly reduced blood flow, the Cunningham clamp was the only device ranked positively by all 12 men; 2 of 12 men rated the C3 positively; no men rated the U-Tex positively (Table 3). Conclusions The use of urethral compression device is probably a safe and efficacious alternative available to some men who wish to pursue improved continence following radical prostatectomy. Individualized instruction to cognitively capable men is necessary to ensure appropriate use, comfort, and fit. The Cunningham device was the most efficacious and the most acceptable to users but also contributed to reduced systolic velocity in all men. Clinically, we would recommend that men who are at risk for circulatory impedance such as those with diabetics, not use the Cunningham device.

Table 1

Mean Pad Weights for Various Devices Device Mean Pad Weight (SD) None 122.8(130.8) Cunningham Clamp 17.1(21.2)* C3 32.3(24.3)* U-Tex 53.3(65.7)* *Compared to baseline (p<.05) Table 2 Device Mean Rt Systolic

Velocity (SD) Mean Lt Systolic Velocity (SD)

Mean Rt resistance index (SD)

Mean Lt Resistance Index (SD)

No Device 12.4 (2.8) 12.3 (3.0) 0.90 (0.10) 0.87 (0.10) Cunningham 9.5 (2.3)* 7.3 (3.0)* 0.92 (0.13) 0.86 (0.29) C3 12.4 (5.5) 11.7 (4.7) 0.92 (0.10) 0.92 (0.11) U-Tex 11.9 (4.4) 13.8 (7.3) 0.93 (0.08) 0.91 (0.11) *p< 0.05 compared to baseline

Table 3 Mean Overall Satisfaction (1= good, 2 = acceptable, 3 = unacceptable) Device Satisfaction Score (SD) Cunningham Clamp 1.6(0.5) C3 2.1(0.8) U-Tex 2.3(0.5)* *p>.05 U-Tex compared to Cunningham 79 Noguchi M 1, Shimada A1, Ogata H1, Noda S1 1. Department of Urology, Kurume University School of Medicine URODYNAMIC FINDINGS AFTER RADICAL RETROPUBIC PROSTATECTOMY USING SUSPENSION TECHNIQUE FOR RAPID RECOVERY OF CONTINENCE Aims of Study Urinary incontinence following radical retropubic prostatectomy still remains a common problem. Recent investigations of urethral anatomy have shown that a suspensory mechanism of the urethra is important for rapid recovery of urinary continence following radical retropubic prostatectomy. We examined urodynamic findings after radical retropubic prostatectomy comparing suspension technique to non-suspension technique.

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Methods A total of 45 consecutive patients (mean age 67.6 years) who underwent radical retropubic prostatectomy for localized prostate cancer were prospectively evaluated with multichannel urodynamics including static urethral pressure profilometry and water filling cystometry. The suspension of vesicourethral anastomosis was performed in 33 patients by placement of two stitches, anchored to the pubo-prostatic ligaments, preserving anterior attachment to the pubic bone, and the remaining 12 patients did not undergo the suspension technique. In all patients, the maximal urethral closure pressure (MUCP), functional sphincter length (FSL), maximal cystometric capacity (MCC) and abdominal leak point pressure (ALPP) were measured before the surgery, and at 1 week, 1 month, and 3 months postoperatively, and these parameters were compared between the suspension group and the non-suspension group. In addition, upright cystourethrography findings after surgery were compared on the suspension status between the two groups. Results The continence rates at 1 week, 1 month, and 3 months after radical prostatectomy were 67%, 82%, and 91%, respectively, in the suspension group compared to 0%, 25%, and 50%, respectively, in the non-suspension group. Postoperative ALPP at all measuring points was significantly higher in the suspension group compared to the non-suspension group (Table 1). Upright cystourethrographY after radical prostatectomy in the suspension group showed the better suspension status than those in the non-suspension group (Table 2). There was no difference in MUCP, FSL and MCC at each point following radical prostatectomy between the 2 groups (Table 1). Table 1. Urodynamic results in men with suspension and without suspension before and after radical prostatatectomy Mean No. pts. Pre-ope 1W 1M 3M Significancea MUCP (cmH2O) Suspension 33 68.2 34.1 51.5 62.2 n.s. Non-suspension 12 71.8 28.3 38.3 54.5 FSL (mm) Suspension 33 34.5 8.8 8.3 8.3 n.s. Non-suspension 12 31.9 6.8 7 7 MCC (ml) Suspension 33 375.3 246.8 287.2 331.2 n.s. Non-suspension 12 397.7 224.8 273.8 312.1 ALPP (cmH2O) Suspension 33 86.6 60.7 70.9 74.1 p = 0.0002 Non-suspension 12 82.3 48.3 56.3 48.8 n.s. not significant ANOVA (repeated-measure design). Table 2. Suspension status after radical retropubic prostatectomy No. pts. Mean distance (cm) a Before catheter removal 3 months after the surgery Suspension 33 0.9 0.9 No-suspension 12 1.9 1.8 Significanceb p < 0.001 p < 0.001 Distance to anastomotic level from the upper line of the pubic symphysis on upright cystourethrography. Mann Whitney U-test. Conclusions These observations suggest that fixation of urethral hypermobility by the suspension technique results in rapid recovery of urinary continence after radical retropubic prostatectomy.

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80 Lai H H1, Smith C P1, Teh B S 1, Butler E B1, Boone T B 1 1. Baylor College of Medicine PELVIC RADIOTHERAPY DOES NOT INCREASE THE COMPLICATION RATES OF ARTIFICIAL URINARY SPHINCTER IMPLANTATION Aims of Study Patients with pelvic radiotherapy (XRT) have impaired tissue healing capacity, small vessel occlusion and ischemia, and more complex etiology of incontinence secondary to detrusor hyperactivity and decreased compliance. It is unclear whether XRT increases the complication rates of artificial urinary sphincter (AUS) implantation for intrinsic sphincter deficiency (ISD) because of these adverse factors. Two recent publications revealed conflicting results (1, 2). We present the largest contemporary retrospective series to date to clarify the issue. Methods From November 1992 to May 2002, 152 consecutive patients had AUS (American Medical System 800) surgery by a single surgeon for ISD. 2 of these patients did not have follow-up and were excluded from the study. Among the remaining patients, 50 had a history of pelvic XRT (41 radical prostatectomy, 5 transurethral prostatectomy, 1 prostate cryosurgery, 3 without prostatectomy) while 100 had no history of pelvic XRT (82 radical prostatectomy, 2 cystectomy, 5 transurethral prostatectomy, 11 neurogenic bladder). Patient demographics, pre-operative incontinence and urodynamics, post-operative incontinence, and AUS implantation complications were compared between the XRT and non-XRT groups. Results Mean follow-up was 29.3 (range 1.0 to 104.9) and 30.3 (1.0 to 113.4) months in the XRT and non-XRT groups respectively. Patient age, history of failed collagen injection, pre-operative pad use, post-operative pad use, and post-operative urge symptoms were comparable between the two groups. XRT patients had smaller bladder capacity, earlier sensation and lower detrusor compliance than non-XRT patients in pre-operative urodynamics. In addition, XRT patients were twice as likely (54%) to have bladder neck contracture than non-XRT patients (27%). To eliminate referral bias, all third-party AUS complications that resulted in sphincter revision or removal by our group were excluded. Patients with neurogenic bladders were also excluded (none had XRT). As shown in the table below, pelvic XRT did not increase the complications rates of AUS implantation for ISD: Complications XRT (n=50) Non-XRT (n=89) Infection, exposed device 0 (0%) 7 (7.9%) Urethral atrophy 3 (6%) 13 (14.6%) Cuff erosion 1 (2%) 4 (4.5%) Device malfunction 0 (0%) 8 (9%) Iatrogenic (e.g. pump migration) 0 (0%) 2 (2.2%) It was safe to use 61-70 cm water reservior and activate the sphincter 4 weeks after AUS implantation in previously irradiated patients. Conclusions Pelvic radiotherapy does not increase the complication and/or re-operative rates of artificial urinary sphincters implantation for intrinsic sphincter deficiency. Patients have similar outcome with regard to post-operative continence and urge symptoms whether or not they have received previous pelvic radiation. References Gomha MA, Boone TB. Artificial urinary sphincter for post-prostatectomy incontinence in men who had prior radiotherapy: A risk and outcome analysis. J Urol 2002;167(2 Pt 1):591-6. Walsh IK, Williams SG, Mahendra V, Nambirajan T, Stone AR. Artificial urinary sphincter implantation in the irradiated patient: safety, efficacy and satisfaction. BJU Int 2002; 89(4):364-8.

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81 Fader M1, Bain D1, Cottenden A1 1. University College London PADS AND PRESSURE: AN INVESTIGATION INTO THE EFFECTS OF ABSORBENT INCONTINENCE PADS ON PRESSURE MANAGEMENT MATTRESSES Aims of Study Pressure ulcers and incontinence often co-exist and are more common in older people(1). Urinary incontinence has been found to be a significant risk factor for pressure ulcers (2) and there is a strong association between poor mobility and continence problems (3). Patients using pressure management products are therefore also likely to be using absorbent pads but the effect that pad wearing has on pressure-relieving products is unknown. The aim of this study was to determine the effects that absorbent pads have, in both dry and wet states, on the pressure-relieving properties of standard and pressure management mattresses. Methods An instrumented articulated anthropometric phantom (Patent IPC 94928968.0) with simulated soft body ‘tissues’ in the gluteal and sacral areas was used as the ‘subject’ (Figure 1). The soft tissues of the pelvic region are a silicone polymer compound with the same mean instantaneous static hardness value as the buttock tissues of a cohort of elderly volunteers (mean age 68.2 years, SD 3 years) (4). The silicone compound was moulded in a CNC-generated mould representing the shape derived from numerical topography data acquired by laser scanning the same cohort of volunteers. The phantom is fixed on a ceiling-mounted guidance system for positioning on different surfaces. The phantom produces reproducible pressures (co-efficient of variation around 2%) compared to humans and is the method recommended by the European Pressure Ulcer Advisory Panel (EPUAP) for testing pressure management products (5). A commonly used, commercially available absorbent pad and pant system for moderate to heavy incontinence was selected (Tenaform Super, SCA Hygiene Products AB, Göteborg, Sweden). This was tested with three different mattresses: (A) a standard foam mattress, (B) a visco-elastic foam mattress and (C) a surface-cut visco-elastic foam mattress. Mattresses (B) and (C) are marketed as pressure management mattresses. The phantom was raised and lowered onto the three mattresses in three states: naked, wearing a dry pad and wearing a wet pad following a standard operating protocol. The pressure mapping device Xsensor version 4 (Xsensor Technology Corporation, Calgary, Canada) was used to record the distribution of pressure over the sacral and ischial areas of the phantom. Peak pressure was used as the primary outcome variable and 10 repeats were made on each mattress under each condition. Results The table below shows that the presence of an incontinence pad between the patient and the mattress raises the peak pressure by around 20-25%, a difference that is likely to be of clinical importance. Peak pressures frequently occurred over areas of pad folds. Absorbent pads are folded and compressed for packaging and creases occur in the pad folds. Additional testing showed that pads that were ‘smoothed’ by hand had significantly lower peak pressures than ‘unsmoothed’ pads. There were no significant differences between wet and dry pads. Mattress Naked

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A. Standard foam 70.9 (SD1.6) 87.3 (SD6.1) 15.06-17.73 B. Visco-elastic foam 71.2 (SD2.57) 85.2 (SD6.42) 9.4-18.59 C.Surface-cut foam 67.6 (SD2.27) 82 (SD4.64) 10.96-17.83 The graph below shows the data and standard deviations from 10 repeats on each mattress under each condition.

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Peak pressures (SD) recorded from three mattresses (standard, visco-elastic, surface-cut foam)under three conditions (naked, dry pad, wet pad)

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Figure 1 Anthropometric phantom Conclusions This study demonstrated that absorbent pads have a substantial adverse effect on the pressure redistribution properties of mattresses. Pad folds appear to contribute to this effect. Absorbent pad manufacturers should consider engineering pads that minimize disruption to pressure management. Further examination of continence and pressure management products is necessary to establish optimum combinations. References 1.Guralnik JM, Harris TB, White LR, Cornoni-Huntley JC. Occurrence and predictors of pressure sores in the National Health and Nutrition Examination survey follow-up. J Am Geriatr Soc 1988 Sep;36(9):807-122. 2.Spector WD, Fortinsky RH (1998) Pressure ulcer prevalence in Ohio nursing homes:clinical and facility correlates. J Aging Health 10(1) 62-80 3. Sgadari A, Topinkova E, Bjornson J, Bernabei R. Urinary incontinence in nursing home residents: a cross-national comparison. Age Ageing 1997 Sep;26 Suppl 2:49-54 4.Bain DS, Nicholson N, Scales JT.A phantom for the Assessment of Patient Support Systems. Med Eng & Phys. 21 (1999).293-301 5. European Pressure Ulcer Advisory Panel, Working Group 2, Guidelines for the measurement and presentation of interface pressure data on support surfaces, January 2002

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82 Clarke-O'Neill S 1, Pettersson L 1, Mandy F1, Cottenden A 1, Brooks R 1 1. University College London PRODUCT FOCUS: DISPOSABLE PADS FOR WOMEN WITH LIGHT INCONTINENCE – MAKING THE RIGHT PRODUCT CHOICE. Aims of Study Studies from around the world estimate the prevalence of urinary incontinence in community dwelling women to be between 9% and 72% (1). Absorbent pads are one of the main methods used for managing incontinence and represent a substantial cost for health services. However, with a bewildering array of products available at a wide range of prices there is little independent guidance available to help users, professionals and purchasers to make informed purchasing choices. The aim of this study was to evaluate and report on the current range of disposable pads for women with light incontinence. The products evaluated were those on the UK market in September 2000, but the majority of the pads tested were also available throughout Europe and in the US.

Methods Sixty women aged between 50 and 91 (mean age 68.5) tested each of the 12 products for five days. The products were randomised using Latin squares (2) to enable a balanced order of testing. Pad performance was measured using two tools:

A product performance questionnaire - subjects rated sixteen aspects of pad performance as good, okay or poor. They also rated their ‘Overall opinion’ of the pad on the same scale and this question was used as the primary outcome variable (POV).

A pad leakage diary – subjects rated leakage by weighing the used pads using a spring balance and recording the amount of leakage from the product (none, a little, a lot).

Statistical analysis was carried out using SAS (Statistical Analysis Software, version 8). Comparisons were made between the products using logistic regression modelling that takes into account the repeated observations from each subject. The modelling relates the probability of a particular outcome (e.g. ‘Overall opinion’ is ‘good’) to levels of factors that could affect outcome (e.g. type of pad, test order). Each pair of products were compared using a significance level of 0.1% which, with pairwise comparisons between the 12 products, results in an overall significance level of just above 5%. It is necessary to use this low level of significance (0.1%) as it reduces the likelihood of finding statistically significant differences between the twelve products by chance. Results Prior to the start of the study a group of users were consulted on the pad features that they considered important. Leakage, fit and smell were rated as first or second most important by the greatest proportion of the 43 female respondents (67%, 51% and 26%, respectively). These aspects of pad performance clearly represent key user priorities and it was reassuring to see statistically significant differences between products in these areas. In general all of the pads performed adequately across all 16 areas on the product performance questionnaire and in the pad leakage diary. The data from the product performance questionnaires showed that whilst all pads did perform satisfactorily three pads performed particularly well and represented good all round products, whilst one pad stood out as the least successful performer, see Table 1. The pad leakage diary revealed that all the products performed generally well in terms of ability to prevent leakage of urine: data showed that at 10g of urine 81% to 95% of all pads did not leak ‘at all’. This is very encouraging as leakage is one of the most important aspects of pad performance for users (3). Most successful products The ‘Prevail extra plus’ and ‘Tena lady extra’ performed particularly well and the proportion of subjects who found them to be ‘good’ was statistically significantly higher than at least one other product in four areas of performance (including fit and smell). For the primary outcome variable ‘Overall opinion’, the proportion of

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subjects who rated these products as ‘good’ (50% and 57% respectively) was statistically significantly higher than for two other products. One other product the ‘Anamini extra’ also performed particularly well, the proportion of subjects who found this product to be ‘good’ was statistically significantly higher than at least one other product in six areas of performance (including leakage and smell). For the primary outcome variable ‘Overall opinion’ 41% of subjects rated this product as ‘good’ and this proportion was statistically significantly higher than for one other product. Least successful product The ‘Attends 3’ was the least successful product tested, the proportion of subjects who found this product to be ‘poor’ was statistically significantly higher than at least one other product in five areas of product performance (including leakage). When subjects were asked to rate their ‘Overall opinion’ of this product 49% rated it as ‘poor’. This proportion was statistically significantly higher than for two other products. Conclusions The results of this evaluation show that in general, most products performed adequately on most performance aspects. However, there were clearly some pads that performed better than the rest of the group and were good all round performers. One pad in particular performed less well than the rest of the group. The results indicate that it is certainly possible for individuals to purchase pads that perform well in key areas and are also reasonably priced. But given that some pads did perform substantially better and some substantially worse than the rest of the group, those wishing to purchase pads in large quantities for contract purposes would be wise to use this evaluation as a guide and to buy samples of a variety of products to try before making a large purchasing commitment. Table 1 Proportion of subjects rating products as ‘good’, ‘Okay’ ‘Poor’ in key performance areas and POV.

% of subjects rating Leakage as:

% of subjects rating Fit as:

% of subjects rating Smell as:

% of subjects rating Overall opinion as:

Product name

‘Good’ ‘Okay’ ‘Poor’ ‘Good’ ‘Okay’ ‘Poor’ ‘Good’ ‘Okay’ ‘Poor’ ‘Good’ ‘Okay’ ‘Poor’ Abri-san 40 26 34 33 37 31 42 39 19 20 48 31 Anamini 58 22 20 44 42 15 64 19 17 41 41 17 Attends 3 28 30 42 20 37 43 28 46 26 14 37 49 Celanorm 28 43 30 40 32 28 39 25 16 34 39 27 Contisure 39 44 17 45 40 15 50 39 12 38 46 16 Indasec 55 23 21 38 45 17 55 40 4 47 41 12 Microflex 49 35 16 38 46 17 52 36 12 40 48 12 Molimed 39 39 22 33 31 35 47 43 11 25 41 33 Prevail 53 29 18 45 27 27 58 33 9 50 24 26 Tena lady 52 37 12 56 31 13 56 35 10 57 31 12 Tender 45 41 14 41 37 22 54 34 12 38 40 22 Vlesi-well 33 41 27 26 52 22 47 39 14 30 44 26

Shaded areas indicate that a statistically significant difference was found between this product and at least one other product (P<0.001) References 1. Hunskaar et al Epidemiology and natural history of urinary incontinence, IN ed Abrams, P., Cardozo, L., Khoury, S., Wein, A. Incontinence 2nd edition Health publication Ltd 2002 2. Armitage, P., Berry, G., Statistical methods in medical research. 3rd edition Blackwell Science Oxford 1994 3. Anonymised A multi-centre comparative evaluation: disposable pads for women with light incontinence Wound, Ostomy and Continence Nursing In Press 2003

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83 Yalcin I1, Bump R1 1. Lilly Research Laboratories THE EFFECT OF PRIOR TREATMENT EXPERIENCE AND INCONTINENCE SEVERITY ON THE PLACEBO RESPONSE OF STRESS URINARY INCONTINENCE (SUI) Aims of Study The placebo response of stress urinary incontinence is sizeable but variable. In four large randomized clinical trials examining the role of duloxetine hydrochloride in the treatment of women with stress urinary incontinence, the placebo reduction in incontinence episode frequency (IEF) varied between 27 and 40%. Other authors have reported placebo effects as high as 75% [1]. The aim of the current analysis was to examine the relationship between previous treatment experience and baseline incontinence severity with placebo response. Methods 921 assessable women aged 24 to 83 years received placebo in four 12-week randomized clinical trials evaluating pharmacological therapy for SUI in 16 countries in Africa, Australia, Europe, North America, and South America. Predominant SUI was diagnosed using a clinical algorithm demonstrated to be 90.2% predictive for urodynamic stress incontinence. Subjects were randomly assigned to receive placebo (n = 955) or duloxetine (n = 958) for 12 weeks. Weekly incontinence episode frequency (IEF) was calculated before and after randomization using subject-completed real-time paper diaries. At baseline, subjects reported their experience with prior continence surgery and with current pelvic floor muscle training (PFMT) using standardized questions. Analysis included Pearson correlations and the Wilcoxon two-sample test. All analyses are based on intent-to-treat principles. Results The placebo group had an average IEF of 17 per week. 55% of assessable placebo-treated subjects averaged ≥14 IEF/week, 11.8% had prior continence surgery, and 16.5% currently performed PFMT. The overall median decrease in IEF with placebo was 33% but ranged from a low of 11% to a high of 57% for individual countries. The placebo response was lower in women with more severe SUI (p=.07), in those who had prior continence surgery (p=.26), and for those using PFMT (p=.02). In comparison, decreases in IEF with active treatment were nearly identical in these subgroups (Table).

Current PFMT Prior Surgery Baseline IEF Severity No Yes No Yes <14/wk ≥14/wk

Placebo 33.3% 23.6% 33.3% 25.0% 36.4% 29.6% Duloxetine 51.5% 51.9% 50.0% 52.0% 50.0% 53.3%

Table. IEF reduction by subgroup for placebo and duloxetine

Figure. Placebo response versus PFMT use rates by country. Diamonds = countries in Western Europe, North America, and Australia with at least 18 subjects; squares = countries in Western Europe with 8 or fewer subjects; triangles = countries outside Western Europe, North America, and Australia. rho = 44; p < 0001

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There was a significant positive correlation (rho = .44; p < .0001) between the placebo response within a country and that country’s utilization rate for PFMT (Figure). The IEF reduction/PFMT utilization rate relationships ranged from a 57% IEF reduction with placebo in a country with a 0% PFMT utilization rate to 21% reduction in a country with a 46% PFMT utilization rate. There were geographic differences in placebo response that paralleled the utilization rates for PFMT (Figure). Conclusions Treatment naivety, as reflected by low utilization rates of PFMT, seems to be a significant predictor of an increased placebo response in clinical trials for SUI. There is also a trend for an enhanced placebo response in women with less severe SUI and for a lower placebo response in those with a history of prior continence surgery. References 1. CE Dubeau, V Khullar. Drug impact on the SUI component of mixed incontinence: is it all placebo effect. 2002 American Urogynecologic Society meeting, San Francisco. 84 Millard R 1, Moore K2, Yalcin I 3, Bump R 3 1. Prince of Wales Hospital, 2. St. George Hospital, 3. Lilly Research Laboratories DULOXETINE VS. PLACEBO IN THE TREATMENT OF STRESS URINARY INCONTINENCE: A GLOBAL PHASE 3 STUDY Aims of Study Duloxetine hydrochloride, a potent and selective inhibitor of serotonin (5-HT) and norepinephrine (NE) reuptake, is thought to increase efferent output from Onuf’s nucleus via stimulation of pudendal motor neuron alpha-1 adrenergic and 5 HT-2 receptors, resulting in enhanced contractility of the rhabdosphincter (1). Trials in North America and Europe have provided evidence for the safety and efficacy of duloxetine as a pharmacological agent for the treatment of stress urinary incontinence (SUI) (2,3). The aim of this study was to assess the efficacy and safety of duloxetine in women with SUI in diverse populations on four continents. Methods 458 women aged 27-79 were enrolled in this double-blind, placebo-controlled study. The study was conducted at 38 study centres in Argentina, Australia, Brazil, Finland, Poland, South Africa and Spain. The case definition was a predominant symptom of SUI with a weekly incontinence episode frequency (IEF) ≥7, the absence of predominant urge symptoms, normal diurnal and nocturnal frequencies, a bladder capacity ≥400 mL, and both a positive cough and stress pad test. Women on stable pelvic floor muscle training (PFMT) and those with prior continence surgery were not excluded but no new PFMT was introduced. After a 2-week observation period and a 2-week placebo lead in period, subjects were randomly assigned to receive placebo (N=231) or duloxetine 40 mg bid (N=227) for 12 weeks with three follow-up visits at 4-week intervals. Outcome variables included IEF, recorded on real-time diaries for one week prior to each visit, the Patient Global Impression of Improvement (PGI-I) Scale, and the Incontinence Quality of Life (I-QOL) questionnaire. Van Elteren’s test (a stratified Wilcoxon test) was used to analyze median percent changes in IEF where the stratification variable was weekly baseline IEF (<14 and 14 or greater). Analysis of covariance was used to analyze mean changes in average voiding interval and I-QOL. The PGI-I, which is a 7-point scale ranging from “very much better” to “very much worse.” was analysed using Cochran-Mantel-Haenszel test. The responses “very much better”, “much better”, and “a little better” (scores 1, 2 and 3) were grouped into a single “better” category. Analyses were performed according to intent-to-treat principles.

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Results The mean baseline IEF was 18.4/wk for assessable subjects; 56% had a baseline IEF ≥14. Overall current use of pelvic floor muscle training (PFMT) was 9.0% (country range 2.6% to 27.3%). There was a significant decrease in IEF with duloxetine compared with placebo with comparable significant improvements in quality of life (table). These improvements with duloxetine were associated with significant increases in voiding intervals compared with placebo (change of 20.4 versus 8.5 min, p < .001), were reported within 4 weeks of commencing therapy, and persisted for the duration of therapy. Discontinuation rates for adverse events were 1.7% for placebo and 17.2% for duloxetine (p < .001) with nausea being the most common reason for discontinuation (3.1%). Nausea was also the most common adverse event, occurring in 25.1% of duloxetine subjects compared with 3.9% of placebo subjects (p < .001). Nausea was mild or moderate in most subjects (80.7%) and did not worsen in any subject. 88% of women who experienced nausea while taking duloxetine completed the trial. 60% of nausea resolved by 7 days, 86% by one month.

Conclusions The data demonstrate improvements in incontinence and quality of life with duloxetine that are consistent with those observed in two other phase 3 trials in Europe and North America. The placebo response was over 10% higher in this trial, possibly related to a greater number of treatment naïve subjects, as reflected by a 9% prevalence of current PFMT compared with 19.1% and 17.4% in the other phase 3 trials (p<.001). References Effects of duloxetine, a combined serotonin and norepinephrine reuptake inhibitor, on central neural control of lower urinary tract function in the chloralose-anesthetized female cat. J Pharmacol Exp Ther 1995;274:1014-24. Duloxetine versus placebo in the treatment of stress urinary incontinence (SUI). Neurourology and Urodynamics 2002;21(4):383-4. 85 Karantanis E1, Tate S1, Wang K1, Fynes M1, Stanton S1 1. St George's Hospital, London DOES THE SEVERITY OF STRESS INCONTINENCE INFLUENCE OUTCOME FOLLOWING TVT ? Aims of Study Reported TVT continence rates at two years vary between 66%(1) and 86%(2) but the predictors of failure are unclear. We hypothesised that women with severe urodynamic stress incontinence (USI) have a lower TVT cure rate as they may require greater mid-urethral support. The 24-hour pad test is applicable to test this hypothesis, as it is repeatable (3) and correlates with the 24-hour urinary diary (4). Objective cure, may be defined as the return of pad test weight to within the normal range. We aimed to analyse the relationship between the severity of pre and post-operative pad test weights in women with primary and secondary (prior continence surgery) USI to determine whether severity has any prognostic significance as this has not previously been investigated.

IEF Decrease (all subjects)

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Duloxetine 54% 55% 10.3 74% Placebo 40% 42% 6.4 64% P .05 .022 .007 .03

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Methods Prior to commencing the study, the definition of “dry” on 24 hour pad test was briefly re-evaluated, using the Unit’s standard absorbant pad on 19 continent women. In this small sample the upper 95th centile was 10.3g (mean value 4.8g). A consecutive group of women with a sole diagnosis of USI and no prolapse were enrolled. Exclusion criteria were: >grade 1 cystourethrocele/rectocele, post-void residual (PVR) >100mls, peak flow rate <15mls/sec, and detrusor overactivity. A 24-hour pad test was completed during a 24-hour urinary diary, with an International Consultation on Incontinence Questionnaire (ICIQ-SF) both pre- and post-operatively at 6 weeks and again at 6 months. Correlation between pre and post-operative results was determined using Kendall’s Rank Test. Cure was defined as a 24 hour pad weight gain within the 95th percentile for continent women (10.3g) in the absence of dysfunctional voiding (residual volume >100mL). Cure rate was calculated using all women as denominator, and non-returned pads considered failures. Subjective cure was defined as “never leak” on Q1 of the ICIQ-SF. The 24-hour pad test was performed using Tena comfort mini extra® pads (SCA Hygiene Products, Sweden) which weigh 24 grams (containing 16 grams of pulp with 4 grams of absorbent powder). Five pre-weighed pads were provided per patient in a snap-lock bag to prevent evaporation. After a 24-hour period the pads were returned and the used pads weighed on the same day. Pre and post pad weights were determined using beam balance scales with accuracy to 0.1 grams (C300 Ohaus Scale).

Results Current results at 6 weeks are described, and the complete data set at 6 months is nearing finalisation. Fifty-five consenting women with USI undergoing TVT were evaluated. They were mean age 55(SD+/-11), median parity 2(SD+/-1) and mean BMI 29(SD+/-6). Forty-six women completed the pre-operative 24-hour pad test. Nineteen (35%) had undergone one or more previous continence operations. The median pre-operative pad weight for primary and secondary USI was 47g (IQR15-111) and 76g (IQR 20-120) respectively, with no significant difference (Mann-Whitney U; p=0.1). At six-weeks only 39/55 completed the pad test. Of those who did not, 9 were cured and 2 much improved and did not want to do the test; 4 had new urge incontinence; and 1 was lost to follow-up. No patient required self-catheterisation. In one patient the PVR was 200mL but was normal 4 weeks later. The cure rate (using 95th percentile) was 60% (33/55) although of those actually tested it was 85%. There was no difference in cure rate between primary and secondary cases (Fischer’s Exact P=0.49). The subjective cure rate was 20/55 (38%). 30/55 women have completed six-month follow-up thus far, of which 25 have returned pad tests. All patients cured at six weeks remained cured at 6 months. Pre-operative pad test weights did not correlate with post-operative results at 6 weeks (tau-b=0.101; P=0.43) or 6 months (tau-b 0.24; P=0.13), nor did ICIQ-SF scores (6-weeks P=0.5; 6 months P=0.9). Fig.1 shows the effectiveness of the TVT at 6 weeks regardless of pre-operative severity. Figure 1. 24-hour pad test results pre and post TVT

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Conclusion Pad testing compliance was poor which may have lowered the cure rate, as cured patients were reluctant to perform the test. This was previously found by Hilton(5), who also found subjective cure rates to be lower than pad cure rates(5). Possibly 24-hour pad tests may miss the infrequent leakage episodes which make patients unable to say they ‘never leak’.

The TVT seems to cure independently of the preoperative severity of USI, disputing the hypothesis that severity is a bad prognostic factor for TVT. Presumably therefore, heavier leakage on a 24-h pad test is not a function of worsening periurethral pathology, but may reflect greater numbers of leakage episodes, as previously suggested (4), possibly in more active women, or those with frequent coughing. However, patients with urge incontinence will also have a positive pad test leading to a worse outcome.

References 1. BMJ 2002. 325(2355): 67 2. BJOG 1999. 106(4): 345-350 3. Neurourol Urodyn 1989. 8: 579-587 4. Neurourol Urodyn 2002. Aug 21(4): 24 5. BJOG 2002 Oct;109(10):1081-8 86 Kondo A1, Kimura K1, Isobe Y 1, Kamihira O 1, Matsuura O1 1. Komaki Shimin Hospital A RANDOMISED CONTROL TRIAL OF TENSION-FREE VAGINAL TAPE IN COMPARISON WITH PUBOVAGINAL SLING IN THE TREATMENT OF STRESS INCONTINENCE Aims of Study Tension-free vaginal tape (TVT) surgery was reported in 1995 (1). A 5-year follow-up study (2) found that subjective and objective cure was observed in 85% of 72 patients with 5% failure. The real value of TVT needs to be assessed by randomised control trials and so far there are only 2 such studies. One study (3) randomised 344 women to either TVT or colposuspension and observed that objective cure rates were 68% in the former and 57% in the latter. The other (4) allocated 68 patients to TVT and 74 to porcine dermal sling, and authors obtained the subjective cure rate of 85% in the former and 89% in the latter. Our aim is to evaluate surgical outcomes of TVT compared to pubovaginal sling (PVS) operation in a prospective randomised manner. Methods A total of 61 women were recruited for surgical trials in our clinic from September 1999 to October 2002. Of the patients 4 withdrew from the study and 57 women were available for the present assessment. Twenty-nine women were randomly assigned to tension-free vaginal tape procedure and 28 to pubovaginal sling operation. The women attended the clinic 3, 12 and 24 months after operation. Objective cure was consistent with complete continence in response to strong coughs 3 to 4 times in a row in a lithotomy position with intravesical water of 250 to 300ml. Subjective assessment was based on a questionnaire that asked women presence of incontinence and provided 5 answers, i.e., complete continence, only slight leakage with strong physical exercises, improved but still lose urine, no change, or got worse. Either the first or second answer was regarded as subjective cure. A follow-up period ranged from 3 to 24 months with 54% of women having completed a 24-month visit. While the vaginal tape procedure was carried out under local anesthesia, the pubovaginal sling operation was performed under epidural anesthesia by supporting the bladder neck with the rectus fascia of a 5 cm in length. Both ends of the fascia were sutured and elongated with non-absorbable threads. Continence rates were assessed by Kaplan-Meier survival analysis with log rank statistical significance at p<0.05.

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Results Patients’ characteristics of 2 groups are comparable (Table). All women were urodynamically diagnosed as having either stress incontinence (54 patients) or mixed incontinence (3 patients). Concomitant surgery was performed in 6 women in the TVT group and 5 in the PVS group: anterior and/or posterior colporrhaphy in 6, vaginal hysterectomy in 2, and Le Fort operation, tube ligation, incision of the external orifice 1 each. Intraoperative complications occurred in 11 patients, injury to the urethra or bladder in 6 women of the TVT arm and in 5 of the PVS arm. Revision surgery was required 7 days after surgery in 4 women of the PVS because of residue more than 100ml. Neither wound infection nor tape erosion were encountered. Kaplan-Meier cumulative objective cure rates were 68.4% for the TVT and 45.7% for the PVS at 24 months where difference was not statistically significant (P=0.072) (Fig. 1). The subjective cure rates were much better, namely 85.9% for the TVT and 71.8% for the PVS (P=0.186) (Fig. 2). Objective and subjective cure rates of vaginal tape are very similar with those reported by Ward and Hilton (3) and Arunkalaivanan and Barrington (4), respectively.

Conclusions The most crucial surgical step is how to support the mid-urethra or bladder neck with minimal or no tension in both surgeries. It is likely that low objective cure of the PVS is attributed to repeated assaults of pressure rises and downward movements of the bladder neck that, in turn, stretched the rectus fascia or jeopardized suture points at each end of the fascia. On the other hand, the vaginal tape does not become loose or elongate because the mid-urethra is rather immobile and fixed beneath the pubic bone resulting in the higher cure rate. In conclusion the tension-free vaginal tape is promising because of less surgical invasiveness, less postoperative complications and objective cure at 2 years being comparable with pubovaginal sling. References 1. Ulmsten U, Petros P. Scand J Urol Nephrol 29: 75-82, 1995. 2. Nilsson CG, Kuuva N, Falconer C, Rezapour M, Ulmsetn U. Int Urogynecol J 12 (Suppl 2): S5-S8, 2001. 3. Ward K, Hilton P. BMJ 2002; 325: 67-70. 4. Arunkalaivanan AS, Barrington JW. Int Urogynecol J14: 17, 2003. Table. Characteristics of 57 patients. Group Age 60-min pad-test

(g/hr) Intrinsic sphincter deficiency

TVT (n=29) 32-91(m=59) 0.2-75.5 (m=22.2) 16 women (55%) PVS (n=28) 30-75 (m=54) 1.3-139.1 (m=28.4) 15 women (54%)

0

20

40

60

80

100 Cure Ra tes

0 3 6 12 24Months

Object ive Evalua t ion

Fig. 1. Objective cumulative cure rates at 24 months were 68.4% for TVT (straight line) and 45.7% for PVS (dotted line).

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0

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0 3 6 12 24Months

Subject ive Eva lua t ion

Fig. 2. Subjective cumulative cure rates at 24 months were 85.9% for TVT (straight line) and 71.8% for PVS (dotted line). 87 Paraiso M F1, Walters M1, Karram M2, Barber M1 1. The Cleveland Clinic Foundation, 2. Good Samaritan Hospital LAPAROSCOPIC BURCH COLPOSUSPENSION VERSUS THE TENSION-FREE VAGINAL TAPE PROCEDURE: A RANDOMIZED CLINICAL TRIAL Aims of Study To compare the laparoscopic Burch colposuspension (LBC) with the Tension-Free Vaginal Tape procedure (TVT) for efficacy and safety. Methods Seventy-two women from two institutions were randomized: 36 LBC and 36 TVT. Multichannel urodynamics were performed preoperatively and one year after surgery. Inclusion criteria were primary urodynamic stress incontinence, points Aa and Ba by Pelvic Organ Prolapse Quantification (POPQ) examination at 0 (the hymen) or above, and no concomitant surgeries for anterior vaginal wall prolapse. Exclusion criteria were an abdominal leak point pressure < 60 cmH2O and presence of detrusor overactivity on preoperative urodynamic investigation. A research nurse administered the Urinary Distress Inventory (UDI), the Incontinence Impact Questionnaire (IIQ), and pelvic examinations using the POPQ system preoperatively, six months, one year, and two years after surgery. Voiding diaries were collected at one and two years. Patients underwent office cystometry and cough stress test at two years after surgery. Primary outcome was objective cure defined as no evidence of urinary leakage during postoperative urodynamic studies. Secondary outcomes included subjective continence, operative time, complications, length of stay, POPQ and Q-tip examinations, urinary diaries, and quality of life. Continuous variables were compared with two-tailed t-test and categorical variables were compared with Fisher’s exact test. Kaplan-Meier survival curves were generated for the development of symptoms of incontinence postoperatively and comparisons were made with the log rank test. Number of incontinence episodes recorded on the bladder diary and UDI and IIQ scores were compared using repeated measures ANOVA. Results Thirty-six patients were allocated to each group. In the LBC group, 1 patient withdrew prior to surgery and 4 subjects were lost to follow-up after surgery. In the TVT group, 1 patient died unrelated to surgery prior to follow-up and 5 subjects were lost to follow-up. Thus, 31 LBC and 30 TVT patients were analysed with a mean follow-up of 18.8 months (range 6-43). Both groups were similar with respect to demographics and concomitant procedures performed except more adhesiolyses were done in the LBC group. Mean

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operative time was significantly greater in the LBC vs. TVT groups (p=.0009). Intraoperative complications included 3 conversions to laparotomy in the LBC group and 2 cystotomies in the TVT group. Postoperative hospital stay, analgesia requirements, and complications were similar between groups. No differences were found in mean voiding times and no patients required suprapubic tube drainage > 19 days. One patient from each group required readmission: 1 for pyelonephritis in the LBC group and 1 for physical rehabilitation in the TVT group. One patient in the TVT group required mesh transection for urinary urgency; another patient required conservative management for vaginal erosion of the TVT mesh. Multi-channel urodynamic studies in 26 LBC and 28 TVT patients showed a significantly higher rate of urodynamic stress incontinence at one year in the LBC group, 23% vs. 3.6% (p=.046). Detrusor overactivity was more common in the TVT vs. LBC group: 13.8% vs. 3.9% (p=0.35). Voiding dysfunction was similar between groups. There was a significant improvement in the number of incontinent episodes/week and UDI and IIQ scores in both groups at 1 and 2 years after surgery (p<.001). However, postoperative subjective symptoms of incontinence (stress, urge and any) were reported significantly more often in the LBC group than the TVT group (p<.03 for each category). There was no significant difference in postop vaginal support as measured by POPQ, however urethral mobility was significantly greater in the TVT group (mean straining angle 40+ 3.8) than the LBC group (mean straining angle 21+3.7). Conclusions The TVT procedure results in significantly greater objective and subjective cure rates for urodynamic stress incontinence than the laparoscopic Burch colposuspension. Although LBC is associated with a longer mean operative time, both groups are similar with respect to length of hospital stay and intraoperative and postoperative complications. 88 Mansoor A1, Védrine N1, Darcq C1 1. Centre Hospitalier Issoire SURGERY OF FEMALE URINARY INCONTINENCE USING TRANS-OBTURATOR TAPE (TOT) : A PROSPECTIVE RANDOMISED COMPARATIVE STUDY WITH TVT. Aims of Study TVT is now considered as gold standard technique to treat stress urinary famale incontinence. It give good results but has some morbidity and some life thretening complications have been described. A new technique described in France by Delorme, the TOT is said to reduce these complications. The aim of this study isto evaluate the results and morbidity of the trans-obturator tape by comparing it with a classical technique TVT. Methods We have started, in septembre 2001, a prospective randomised and comparative study concerning 200 patients with stress incontinence associated or not with prolapse. The study is still going on. The first 102 patients operated the first year have been evaluated with a mean follw up of 6,17 months. Preoperatively, standardized uro-gynaecologic questionnaire was fulfilled, urodynamics and ultrasound are performed in every patient. Before the operation the technique is randomly drawn using blinded envelopes containing the same number of TOT and TVT procedures. If prolapse surgery is associated, the sub uretral tape is put at the end of the operation. In the TOT procedure, a sagitttal 2 cm vaginal incision is made at mid urethra. After parauretral bilateral dissections of the vaginal wall up to the pelvic fascia, a small incision is made bilaterally one centimetre lateral the ischio-coccygeus ramus at the level of the clitoris. A specific needle is used to perforate the obturator membrane and keeping close contact with the bone, turns around the ischio-coccygeus ramus. A finger tip is introduced in the space between the vagina and urethra up to the pelvic fascia and waits for the tip of the needle. The needle follows the finger up to the vaginal incision. A Prolene tape obtained by cutting a tape 11 mm large and 30 cm long from a mesh 30X30 cm is attached to the needle which is then removed from the obturator foramen. The same technique is used on the other side to pass the other

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extremity of the tape. Cystoscopy is performed and stress test, is used to position the tape under the urethra in the same way as TVT. The follow up consisted of a clinical evaluation, a one-hour pad test, uroflowmetry, residual urine as well as a self questionnaire evaluating the subjective results. Results The study concerns 48 TOT and 54 TVT. There is no difference between the two groups concerning age, history and associated surgery. Urinary complications are more frequent in TVT group, 5 bladder perforation and 1 urethral laceration versus zero bladder injury in the TOT group. No haematoma in either group. The results on stress incontinence is the same in both groups, 93% of patients in TVT group are cured, versus 96 % in TOT group. Urge incontinence is cured in 60% of patients in TVT group and 80% in TOT group. De novo urge incontinence is present in 7% of TVT group and 4% of TOT group. Frequency is cured in 70% of patients in TVT group and 79 % of TOT group. De novo frequency happened in 19% and 3% of patients respectively. Five patients in TVT group and 1 patient in TOT group had retention and needed lateral section of the tape. They restored satisfactory micturation and are dry. The Prolene° tape is well tolerated in both group, we did not find any exposition of the materiel. In France the TVT costs 371,52 Euros and a Prolene° mesh 80,49 E, the net economy for the hospital is 291 Euros per operation. In our department we operate 150 patients per year which means an annual economy of 43 650 E. Conclusions Mid sub urethral Prolene tape put in a similar way to TVT up to fascial penetration gives the same results on stress incontinence cure rates. The TOT does not pass through the Retzius space and reduce significantly urinary complications and hematomas. It eliminates completely life threatening complcations such as intestinal perforation or large vessels traumas. It seems in this preliminary study that the TOT creates less irritative bladder symptoms. This is to be confirmed in the remaining cases. The home made trans-obturator tape gives the same results as TVT procedure and allows substantial economy to hospital and the society. This economic and safe technique can thus be proposed to treat urinary female incontinence. 89 DasGupta R1, Critchley H2, Dolan R2, Fowler C1 1. National Hospital for Neurology & Neurosurgery, 2. Department of Cognitive Neuroscience A PET STUDY TO ASSESS SUPRASPINAL RESPONSE TO SACRAL NEUROMODULATION IN WOMEN WITH URINARY RETENTION Aims of Study Sacral neuromodulation has been shown to restore voiding function in women with urinary retention attributed to urethral sphincter overactivity. Although the mechanism of action is not established, there is strong evidence to suggest its effect is on the afferent innervation. Functional brain imaging is a useful tool to localise the cerebral areas involved in central processing of visceral information. Previous studies have demonstrated the role of brainstem regions in relaying afferent information during urine storage and activation of other areas during micturition. Women with this type of retention characteristically have their sensation of bladder filling restored by neuromodulation. We have therefore aimed to investigate the central effects of chronic neuromodulation in these patients by a series of Positron Emission Tomography (PET) scans with stimulation on and off. This was contrasted with scans in healthy female control subjects. Methods With the approval of the local Ethics Committee and a current Radionuclide licence, a 2x2 experimental paradigm was used in this PET study. A Siemens ECAT scanner was utilised with the standard oxygen-15 bolus technique. We performed 12 PET scans in healthy female volunteers (aged over 40), 6 scans with the bladder empty and 6 with the bladder full. Before each scan we measured the bladder volume (with a portable ultrasound scanner) and recorded the sensation of fullness (using a validated scoring system).

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Women with a permanent sacral nerve stimulator for retention had 6 scans with the stimulator switched on and 6 with it deactivated. During each session, the bladder was empty in 3 scans and full in the other 3 (by natural filling). The order for all scans was counterbalanced. The images underwent standard normalization, realignment and smoothing before analysis using Statistical Parametric Mapping (SPM99). Covariate analysis was also performed to assess relationship between specific brain activity and sensation of bladder fullness. Results We recruited 8 healthy female volunteers (aged 40-62) and 6 women with urinary retention successfully treated by neuromodulation (aged 39-52). In the control subject group analysis, areas activated when the bladder was full (compared to being empty) were the cingulate cortex, midbrain and pons. In the group analysis for the patients, the pontine activation associated with a full bladder was only seen when the stimulator was switched on. The study design ensured there was no possibility of any carry-over effects of stimulation. Reviewing the effects of interest across the scans revealed that activation of neuromodulation improved the subjects’ ability to discriminate a full versus empty bladder. There was significant correlation between bladder sensation (urge score) and pontine activation (Pearson’s coefficient 0.284) for all subjects. Conclusions Restoration of voiding by neuromodulation seems to involve central mechanisms, involving the brainstem and cingulate cortex. Although this does not establish whether sacral nerve stimulation has its primary effect at a spinal or supraspinal level, nevertheless these results confirm that there are cerebral effects of neuromodulation in urinary retention. The clinical finding that neuromodulation restores the sensation of bladder filling in these women is supported by evidence of improved discrimination of the bladder being full versus empty when the stimulator is activated. Study of the psychophysiological interactions may help us further elucidate the functional relevance of the areas activated in the different conditions. 90 Blok B1, Groen J2, Veltman D3, Bosch R2, Lammertsma A3 1. Urology, AMC, Univ. Amsterdam, 2. Urology, Univ. Rotterdam, 3. PET Center, Free Univ. Amsterdam BRAIN PLASTICITY AND URGE INCONTINENCE: PET STUDIES DURING THE FIRST HOURS OF SACRAL NEUROMODULATION Aims of Study Previous positron emission tomography (PET) studies in healthy volunteers have demonstrated brain structures involved in micturition and continence (1).Furthermore, it was shown recently that specific cortical and subcortical areas are activated during sacral neuromodulation in incontinent patients whom benefited long term from the implant (2).The maximal beneficial effect of neuromodulation is not reached immediately, but after several hours or days. This suggests that neuromodulation induces plastic learning changes in the brain. The present study investigated which brain areas are responsible for these initial learning effects. Methods Eight urge incontinent patients, who responded successfully (>50% less leakage and pad use) to a test stimulation (PNE) during 4 to 6 days with a temporary, percutaneously placed wire electrode, received a permanent implant; an S3 foramen electrode connected to a subcutaneously placed pulse generator (Medtronic Interstim). Patients were placed in the PET camera (ECAT EXACT HR+, Siemens-CTI, USA). During scanning urethral and vesical pressures were measured with an 8 Ch transurethrally placed catheter and a surface EMG of the pelvic floor was registered. Urodynamic examination includes a filling cystometry followed by determination of the voided volume. Filling cystometries are performed in supine position in the PET scanner. The pulse generator was switched on for the first time in the scanner. Each study consisted of 10 scans with 5 times the neuromodulator on and 5 times off in a randomized order. For each emission scan 450 MBq H2O15 was injected intravenously using an infusion pump. The data of each scan were summated and further analyzed using the Statistical Parametric Mapping software (version SPM 99). An

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omnibus P-value less than 0.001 was considered significant. Covariance in time was investigated by giving less weight to the first scans and more weight to the last scans. Results During the initial sacral neuromodulation significant increases in blood flow were seen in the primary motor cortical areas associated with abdominal and pelvic floor musculature, the left lateral cerebellum and the mid cingulate gyrus, but none in the brainstem. Significant decreases during initial sacral neuromodulation were not observed. Conclusions Our data suggest that during the first hours of sacral neuromodulation in urge incontinent patients strong plastic changes are induced in specific brain areas, i.e. the lower trunk motor cortex and the cerebellum. These areas are known to be important for learning of motor behavior. After the initial learning period the pelvic floor and abdominal motor cortical areas are more easily excited and the effects of neuromodulation are prolonged and pronounced greatly. Activation in the mid cingulate gyrus may reflect a temporarily increased awareness of the sense of bladder filling. No plastic changes were seen in areas important for the micturition reflex itself. Future PET studies in patients, in which neuromodulation is ineffective should be carried out to assess whether there are differences in comparison to patients treated successfully. Source of Funding Medtronic Interstim References

1. (Blok et al., Brain, 1997, 1998; Athwal et al., Brain, 2001). 2. (Blok et al., ICS 2002).

91 Siracusano S1, Cucchi A2, Di Benedetto P3, d'Aloia G 1, Knez R1, Ciciliato S1, Carretta R4, Belgrano E1 1. Department of Urology Trieste University, 2. Department of Urology Pavia Hospital, 3. Department of Rehabilitation Centre Udine Hospital, 4. Department of Internal Medicine Trieste University HAEMODYNAMICS CHANGES DURING BLADDER FILLING AND MICTURITION IN NORMAL VOLUNTEERS Aims of Study Micturition is a complex act which activates many areas in the brain and neurological reflexes. Studies in animals have investigated the haemodynamic changes during mieturition and bladder filling. The effects of bladder filling in animals experiments showed an increase in arterial blood pressure and an increase in heart rate (1,2). However these observations have limited impact in the knowledge of human physiology because done in animals and during anaesthesia which alters cardiovascular reflex responses. We performed such investigation in normal men. Methods The study was performed in 75 healthy male volunteers aged 20-70 years. The arterial pressure (systolic arterial pressure, diastolic arterial pressure, mean arterial pressure) was continuosly recorded by plethysmographic technique, the cardiac index was recorded by impedance cardiography (ICG 572). Both the signals were simultaneously used to calculate the total peripheral vascular resistance index. Cardiac index and total peripheral vascular resistance index were recorded during empty bladder, during physiologic bladder filling and during voiding both in sitting position and in upright position. In all subject the micturition was performed in upright position.

A statistical analysis by Student’s test was carried out to verify any significative differences among the above described parameters both in sitting position and upright position.

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Results They are reported in table 1 and 2.

SAP (mm/Hg) DAP (mm/Hg) MAP (MM/Hg) CI

(L/min/m2) TPVRI (dyne x sec x cm-5 /m2)

empty bladder 121.1±19.4 67.2±12.7 85.2±14.1 2.96±0.62 2412.3±659 Student’s test P<0.0001 P<0,0001 P<0.0001 P<0.005 P<0.0001 bladder filling 141.4±20.9 78.4±14.5 99.4±15.4 2.78±0.58 2983±753.3 Student’s test P<0.0001 P<0.004 P<0.0001 P<0.0001 n.s. voiding 163.5±25.7 90.9±17.5 115.1±18.8 2.97±0.63 3219.3±773.4 Tab.1 : evaluation in sitting position SAP (mm/Hg) DAP (mm/Hg) MAP (MM/Hg) CI

(L/min/m2) TPVRI (dyne x sec x cm-5 /m2)

empty bladder 123.6±20.0 71.5±13.0 88.9±14.8 3.11±0.61 2382.6±625.5 Student’s test P<0.0001 P<0.0001 P<0.0001 P<0.0008 P<0.0001 bladder filling 146.8±23.8 82.3±14.9 103.8±16.5 2.95±0.56 2905.9±662.7 Student’s test P<0.0001 P<0.004 P<0.0001 n.s. n.s. voiding 163.5±25.7 90.9±17.5 115.1±18.8 2.97±0.63 3219.3±773.4 Tab.2 : evaluation in upright position Legends: SAP= sistolic arterial pressure; DAP= diastolic arterial pressure MAP= mean arterial pressure; CI= cardiac index; TPVRI= total peripheral vascular resistance index n.s.= not significant Conclusions These results showed, as previously described in animal models, that bladder filling and micturition causes an increase of arterial pressure by modifications of haemodinamics parameters in relation to the age. In particular bladder filling causes an increase of blood pressure in normal volunteers but, contrary to experimental models, a reduced heart rate is observed. References Afferent impulses in the nerves supplying the urinary bladder J. Physiol. 89, 1-13: 1937 The urinary bladder and cardiovascular reflexes. Int J. Cardiol. 23, 11-17: 1989 92 Taniguchi N1, Numata A1, Kaneko S1, Yachiku S1, Mizunaga M2 1. Asahikawa Medical College, 2. Jinyukai Nagayama clinic EFFECT OF NOCTURNAL URINARY DRAINAGE FOR TREATMENT OF BLADDER DETERIORATION IN PATIENTS WITH NEUROPATHIC BLADDER DYSFUNCTION Aims of Study Some patients with spina bifida and neuropathic bladder dysfunction suffer progressive deterioration of vesicalular function and subsequent adverse effects on the upper urinary tract, though they have been regularly undergoing intermittent urinary catheterization, using anticholinergic agents per os / intravesicular, and moisture restriction. Nocturnal polyuria and excessive distension of the bladder is frequently found

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among these patients by careful recording of frequency-volume charts at urination and /or With great attention to nocturnal polyuria, this study was performed to evaluate the effect of nocturnal continuous urinary drainage on the deterioration of function of the lower and upper urinary tracts. Methods Among patients with spina bifida treated by intermittent urinary catheterization for management of neuropathic vesicular dysfunction, four patients (age: 12-28, 2 males and 2 females) with nocturnal polyuria and deteriorating function in the lower and / or upper urinary tracts underwent nocturnal continuous urinary drainage as well as diurnal intermittent catheterization. Vesicular function and urinary tract anatomy were precisely evaluated with conventional urodynamic and radiological (excretory urography, voiding cystography) study. Continuous nocturnal monitoring of detrusor pressure was also performed in two patients. Voided plus drained volume of urine (mean: 600ml, range: 400-1100ml) on waking in the morning was above maximum cystometric capacity (mean: 200ml, range: 150-300ml) in all patients. Only one patient had vesicoureteral reflux (VUR) grade4. Nocturnal continuous drainage was performed with fully informed consent. A specially designed bag catheter (intermittent balloon catheter, DIB Co.Ttd., Tokyo, Japan) was used for repetitive nocturnal indwelling catheterization. Since all patients were experienced in self-catheterization, indwelling and withdrawing of catheters was managed by them. Urodynamic study and radiological examination were repeated after continuous nocturnal drainage for more than three months and the effect of treatment was evaluated. Results High-grade VUR disappeared in one patient after treatment. Three patients exhibited improvement in detrusor compliance (before mean 6.4 ml/cmH20, range:5-7.5 ml/cmH20, after mean 13.3 ml/cmH20, range:10-20 ml/cmH20) and vesicular deformity. No patients had increased frequency of urinary tract infection. Nocturnal continuous monitoring of detrusor pressure, performed in two patients, revealed involuntary detrusor contractions not revealed by conventional water cystometry. Conclusions In patients with neuropathic vesicular dysfunction, special attention should be paid to the nocturnal volume of urine. Considerable overloading of the bladder with urine during sleep might be one of the causes of poor compliance bladder and deterioration of upper urinary tract function. Furthermore, involuntary detrusor contraction, undetected with conventional cystometry, might emerge and increase deterioration of lower and upper urinary tract function. Continuous urinary drainage with an indwelling catheter during sleep not only prevents excessive distension of the bladder and deterioration of urinary tract function, but also reverses deterioration of function and deformity of the urinary tract. It also frees patients from unpleasant bed-wetting and moisture restriction. 93 Yamanishi T1, Furuya N1, Yasuda K 1, Sakakibara R2, Uchiyama T2, Hattori T2, Kamai T1, Tsujii T1, Yoshida K1 1. Dokkyo University, 2. Chiba University COMBINATION OF A CHOLINERGIC DRUG AND AN ALPHA-BLOCKER IS MORE EFFECTIVE THAN MONOTHERAPY FOR THE TREATMENT OF VOIDING DIFFICULTY IN PATIENTS WITH UNDERACTIVE DETRUSOR Aims of Study Cholinergic drugs such as bethanechol chloride and distigmine bromide have been considered to enhance detrusor contractility and promote bladder emptying in patients with underactive bladders. Oral administration of bethanechol and distigmine has been empirically used for underactive bladder dysfunction in the hope of reducing residual urine, but it has not been well standardized for long term therapy and its effect has been questioned. In some placebo-controlled double-blind studies, cholinergic drugs have been shown to be ineffective(1), but recently, oral bethanechol (25 mg q.i.d.) showed a significant reduction of residual volume and an increase of Qmax compared to placebo(2).Recently, alpha-blockers have been reported to be effective for the treatment of voiding dysfunction in patients with neurogenic bladder by

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reducing urethral resistance during voiding(3). A combination of a cholinergic drug and an alpha-blocker has also been reported to be effective in improving urination by enhancing detrusor contractility and lowering urethral resistance in patients with underactive bladder(4). However, whether the combination therapy is better than the monotherapy with a cholinergic drug or alpha-blocker has yet to be proven. The aim of the present study is to compare the effectiveness of a cholinergic drug, an alpha-blocker and a combination treatment for underactive voiding dysfunction. Methods A total of 119 patients with underactive detrusor were entered into a single-blinded randomized controlled study. After the pretreatment observation period of one week, patients were randomly assigned to three groups: the cholinergic group consisting of 40 patients taking cholinergic drugs such as bethanechol chloride (20 mg t.i.d.) or distigmine bromide (5 mg t.i.d.), the alpha-blocker group consisting of 38 patients taking urapidil (30 mg b.i.d.) and the combination group of 41 patients taking both a cholinergic drug and an alpha-blocker. The effectiveness of each therapy was assessed at 4 weeks after the therapy. Urinary symptom scores were assessed by the International Prostate Symptom Score (IPSS). This score was evaluated as a total score, storage symptom scores and voiding symptom scores. Urinary flow rates and postvoid residual urine volume were evaluated at the end of the observation period and after the therapy. Postvoid residual urine volume (ml) and the rate of residual urine (residual urine volume / (residual urine volume + voided volume) × 100 % were measured. Results The total IPSS decreased significantly after the therapy in the alpha-blocker and the combination groups (both p< 0.0001) when compared to the baseline values, but did not decrease significantly in the cholinergic group. The sum of the storage symptom scores decreased significantly in the alpha-blocker and the combination group (p = 0.0068 and p = 0.0031, respectively), but not in the cholinergic group. The sum of the voiding symptom scores decreased significantly in all groups (p = 0.0116, p < 0.0001 and p < 0.0001, respectively). There were significant differences with regard to the sum of IPSS between the cholinergic vs. the alpha-blocker group (p = 0.0008), and the cholinergic vs. the combination group (p = 0.0033), in favor of the latter, respectively. The average and maximum flow rates did not increase significantly after the monotherapy with either the cholinergic drug or the alpha-blocker, but they were significantly increased after the combination therapy as compared to baseline values (p=0.0033 and p=0.0004, respectively). There was a significant inter-group difference between the combination therapy and cholinergic group with regard to maximum flow rate (p=0.0457). In the cholinergic group, the postvoid residual urine volume did not decrease significantly (p=0.1928), but the rate of residual urine decreased significantly (p = 0.0005) after the therapy. The postvoid residual and the rate decreased significantly after the therapy in both the alpha-blocker group (p=0.0043 and p=0.0176, respectively) and the combination therapy group (p=0.0008 and p=0.0001, respectively). In females, average and maximum flow rates increased significantly in the alpha-blocker and combination groups, but not significantly in the cholinergic group. Postvoid residual urine volume and the rate of residual decreased significantly in all groups for all female patients. On the contrary in males, average and maximum flow rates increased significantly in the cholinergic and the combination groups, but they did not change in the alpha-blocker group. Postvoid residual urine volume and the rate of residual decreased marginally significantly in the male combination group. Mild adverse events were observed in 3 of the cholinergic group patients (diarrhea in 1 and abdominal pain in 2 patients), and in 3 of the combination treatment group (diarrhea in 1 and dizziness in 2 patients). The dizziness in the combination group occurred after the daily dose of urapidil was increased to 60 mg, but therapy could be continued after decreasing the dose to 30 mg. In all groups there were no significant variations detected in the systolic or diastolic blood pressure, or the pulse rate, after the therapy was initiated. There was no clear decrease in blood pressure noted in the patients who showed adverse events.

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Cholinergic Group

Alpha-blocker Group Combination Group

Total IPSS Pre-treatment 16.00±6.73 13.37±6.05 15.54±6.37 Post-treatment 14.83±7.80 8.55 ±5.38 10.90±6.88 Intra-group difference p = 0.1241 p = 0.0001 p = 0.0001 Total storage symptom scores Pre-treatment 4.88±2.95 4.26±2.90 5.05±3.05 Post-treatment 4.90±3.35 3.45 ±2.62 3.93±2.65 Intra-group difference p = 0.9530 p = 0.0068 p = 0.0088 Total voiding symptom scores Pre-treatment 11.08±5.59 9.11±4.37 10.49±5.52 Post-treatment 9.73±6.4 5.11 ±4.12 6.98±5.83 Intra-group difference p = 0.0116 p = 0.0001 p = 0.0001 Average Flow Rates (ml/sec) Pre-treatment 4.21±2.15 353±2.26 4.42±2.36 Post-treatment 4.96±2.50 4.25±3.03 6.52±4.94 Intra-group difference p=0.0738 P=0.1095 p = 0.0033 Maximum Flow Rates (ml/sec) Pre-treatment 8.63±3.96 8.53±5.07 9.56±5.99 Post-treatment 9.53±4.37 9.6±5.76 12.68±8.08 Intra-group difference p=0.2323 p=2805 p = 0.0004 Postvoid Residual Volume (ml) Pre-treatment 144.8±118.0 166.1±147.2 162.3±108.3 Post-treatment 122.3±134.6 134.6±123.7 103.9±109.3 Intra-group difference p=0.1928 p=0.0043 p = 0.0008 Rate of Residual Urine (%) Pre-treatment 51.64±27.40 46.99±28.02 54.95±25.88 Post-treatment 35.74±27.82 38.48±8.57 33.20±27.73 Intra-group difference p=0.0005 p=0.0176 p = 0.0001

Conclusions Combination therapy with a cholinergic drug and an alpha-blocker appears to be more useful than monotherapy for the treatment of underactive detrusor. References J Urol 126:640-642,1981. Neurourol Urodyn 21:376, 2002. Eur Urol 35: 45-51,1999. Urology 8: 316-328,1976.

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94 Reitz A1, Knapp P A 1, Müntener M2, Schurch B 1 1. Neuro-Urology, Swiss Paraplegic Center, Balgrist University Hospital, 2. Department of Urology, University Hospital ORAL NITRIC OXIDE DONORS - A NEW PHARMACOLOGICAL APPROACH TO DETRUSOR-SPHINCTER DYSSYNERGIA IN SPINAL CORD INJURED PATIENTS? Aims of Study Patients with spinal cord injuries on suprasacral level often lose the coordination between bladder and urethral sphincter function. This phenomenon known as detrusor-sphincter dyssynergia (DSD) is a common cause of bladder outlet obstruction in these patients and leads to several complications which increase morbidity after SCI. Poor bladder emptying and high bladder pressures can cause recurrent urinary tract infections, structural bladder damage and vesicoureteric reflux, which if left untreated might cause hydronephrosis and at least renal failure. In this study, we hypothesized that the sublingual administration of a nitric oxide donor could be a novel pharmacological approach to DSD in humans with spinal cord injuries. Methods 12 male spinal cord injured patients presenting with neurogenic detrusor overactivity and DSD were studied. 6 performed clean intermittent catheterisation and 6 used suprapubic tapping for bladder emptying. During cystometry and cardiovascular monitoring the bladder was filled until the first bladder contraction accompanied by DSD occurred while bladder and external urethral sphincter (EUS) pressures were continuously recorded. Then the bladder was emptied and the patients received 10 mg of isosorbide dinitrate sublingually. Resting pressures were recorded for 15 min and then cystometry was repeated. Mean values for bladder and EUS pressures were calculated within the resting period and in both fillings within time windows of 30 s, 60 s, 90 s and 120 s after the onset of a bladder contraction and statistically compared by analysis of variance for repeated measurements (level of significance p<0.05). Results Cystometry and drug treatment were well tolerated in all patients. In 7 patients mild headache occurred. Nitric oxide lowered the resting blood pressure and increased heart rate for a period up to 30 min after administration without any clinical significance. During baseline cystometry all studied patients showed a bladder contraction accompanied by DSD. The mean reflex volume was 345 ml (range 194 to 456 ml) and the mean voiding pressure was 65.8 cm H2O (SD 23.0). Post-triggering residual urine volume in the group of 6 patients using suprapubic triggering for bladder emptying was 133 ml (SD 47). Following sublingual administration of 10 mg isosorbide dinitrate the mean EUS resting pressure decreased significantly from 74.9 cm H2O (SD 22.5) at baseline to 63.4 cm H2O (SD 20.8, p<0.01) calculated from 0- 5 min, to 48.4 cm H2O (SD 22.8, p<0.01) calculated from 5-10 min and to 42.4 cm H2O (SD 18.5, p<0.01) calculated from 10-15 min. In the same period the mean resting bladder pressure remained almost unchanged (16.1 cm H2O (SD 6.9) at baseline, 15.1 cm H2O (SD 6.8) from 0-5 min, 17.8 cm H2O (SD 9.5) from 5-10 min and 20.6 cm H2O (SD 12.4) from 10-15 min. Then cystometry was repeated and in all patients a bladder contraction occurred again. The mean reflex volume was 369 ml ranging from 201 ml to 458 ml (non significant vs. baseline reflex volume) and the mean voiding pressure was 62.4 cm H2O (SD 21.9) which was non significant vs. baseline voiding pressure. In the six patients who used to empty the bladder by suprapubic triggering the post-triggering residual volume was with 73 ml (SD 35) significant lower than without isosorbid dinitrate (p<0.001). Mean value calculations within the analyzed time windows of 30 s, 60 s, 90 s and 120 s after the onset of a bladder contraction revealed significant differences for EUS pressures without vs. with nitric oxide (p<0.01) and non significant changes for bladder pressures. Conclusions Oral administration of nitric oxide donors could significantly reduce DSD in all studied patients and improve bladder emptying in the patients with triggered voiding. These results in humans with spinal cord injury indicate that the inhibitory neurotransmitter nitric oxide is involved in urethral smooth and striated muscle regulation and that oral nitric oxide donors mediate a relaxation of the external urethral sphincter. This pharmacological approach could offer a new treatment option for DSD.

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95 Giannantoni A1, Di Stasi S M2, Pizzirusso G1, Mearini E1, Bini V1, Porena M1 1. Department of Urology, University of Perugia, Italy., 2. Department of Urology, "Tor Vergata" University, Rome, Italy INTRAVESICAL RESINIFERATOXIN VERSUS BOTULINUM-A TOXIN INJECTIONS FOR THE TREATMENT OF NEUROGENIC DETRUSOR OVERACTIVITY Aims of Study Intravesical resiniferatoxin (RTX) and botulinum-A toxin injections into the detrusor muscle have been introduced as treatments for refractory detrusor hyperreflexia in patients with neurogenic disease. Preliminary results have shown a significant increase in bladder capacity and in urinary continence with both treatments. However, there are no clinical studies comparing intravesical RTX with botulinum-A toxin injections. We investigated the effectiveness and safety of intravesical RTX and of botulinum-A toxin, comparing their clinical and urodynamic effects over long term follow up in patients with detrusor hyperreflexia due to neurogenic disease. Methods Twenty-five spinal cord injured patients were randomly assigned to receive (a) intravesical administrations of RTX 0.6 microM in 50 ml of 0.9% NaCl over 45 min (n=13), or (b) injections of 300 units of botulinum-A toxin diluted in 30 ml 0.9% NaCl into the detrusor muscle under cystoscopic control (n=12). RTX and botulinum-A toxin treatments were repeated when there was recurrence of urinary symptoms and/or urodynamic worsening. Frequency of daily incontinence episodes, uninhibited detrusor contractions (UDC) threshold and maximum pressure, and maximum cystometric bladder capacity were measured at baseline and during follow up. Local and/or systemic side effects were noted.

Results In the RTX arm, mean follow up was 14.8 ± 3 months; the number of instillations/patient was 8.6 ± 1.9 and the mean time between two consecutive instillations was 51.6 ± 8.2 days. Mean UDC threshold increased from 205.5 ± 69.7 ml at baseline, to 288.7 ± 83.7 at 6 months, to 285.5 ± 85.6 at 12 months and to 273.7 ± 75.8 at 18 months follow up (between baseline and 6 months: p<0.01). Maximum bladder capacity increased from 223.3 ± 68.1 ml at baseline, to 329 ± 72.3 at 6 mos, to 338 ± 63.7 at 12 months and to 330 ± 62.6 at 18 months follow up (between baseline and 6 mos: p<0.01). The frequency of incontinent episodes was significantly reduced. In the botulinum-A toxin arm, mean follow up was 14.2 ± 3.9 months; the number of treatments/ patient was 2.1 ± 0.7 and the mean time between two consecutive injections was 6.8 ± 1.5 months. Mean UDC threshold increased from 190 ± 48.6 ml at baseline, to 326.3 ± 80.9 at 6 months, to 361 ± 62.7 at 12 months and to 383.8 ± 41.7 at 18 months follow up (between baseline and 6 months: p<0.01). Maximum bladder capacity increased from 211.9 ± 49.7 ml at baseline, to 370 ± 79.6 at 6 months, to 415 ± 75 at 12 months, and to 445.3 ± 51.2 at 18 months follow up (between baseline and 6 mos: p<0.01). Six patients were completely continent. We did not observe any local or systemic side effects in both arms. There was a significant increase in UDC threshold (p<0.02) and in maximum bladder capacity (p<0.01) in botulinum-A toxin arm, as compared to RTX at 6, 12 and 18 months follow up. Conclusions Under the conditions imposed in this study, botulinum-A toxin injection into the detrusor muscle is superior to intravesical resiniferatoxin in terms of urodynamic results and clinical benefits in patients with neurogenic detrusor hyperreflexia in a long term follow up. While the efferent parasympathetic innervation to the detrusor is adequately blocked by 300 units botulinum-A toxin, the afferent nervous trasmission is not completely controlled by the present dose of intravesical RTX.

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96 Del Popolo G1, Li Marzi V1, Panariello G1, Lombardi G1 1. Neuro-Urology, Florence ENGLISH BOTULINUM TOXIN-A IN THE TREATMENT OF NEUROGENIC DETRUSOR OVERACTIVITY Aims of Study Botulinum Toxin type A (BTX-A) has utilized in urologic field to treat spinal cord injured patients (SCI) who suffer from detrusor-external sphincter dyssynergia (DESD). In 1990 was published the only double-bind, placebo-controlled study of BTX-A injection into the external urethral sphincter in 5 male patients with SCI and DESD. In 1999, some Authors reported their good preliminary results using BTX-A injections in 30 sites into the detrusor and trigone-sparing. BTX-A is an inhibitor of acetylcholine release at the presynaptic neuromuscular junction, BTX-A inhibits calcium mediated release of acetylcholine vesicles at neuromuscular junction, which results in reduced muscle contractility. BTX-A has catalytic zinc finger motif that may block activity of SNAP-25, protein important in synaptic vesicle fusion. Normally, calcium influx at neuromuscular junction drives fusion and release of neurotransmitter vesicles, process in which SNAP-25 usually participates. Re-sprouting fibers are expected after 2-3 months of injections and they disappear after BTX-A block of synapsis finish. In literature we have data mainly on 300 U.I. of American BTX-A (BotoxTM), but few data about English BTX-A (DysportTM) with different dosages 500, 750, 1000 are reported without a clear profile of efficacy and safety. A recent experience on 87 patients using either 300 U.I. of BotoxTM or 500 to 750 U.I. DysportTM that demontrated the efficacy of the treatment without any adverse effect, but without analysis of any difference using BotoxTM or DysportTM. Other Authors observed hypostenia in patients treated with high-dose intravesical BTX-A injections (300 U.I. BotoxTM or 1000 U.I. DysportTM). The only study published about the results of the repeat injections is based on the use of either toxins. We report our data of a restrospective study about results and adverse effect using DysportTM with different dosages after first injection and multiple re-injections excluding patients treated with BotoxTM or either toxins. Methods Between September 1999 and March 2003 we treated with intravesical BTX-A injection 178 patients. We selected an homogeneous population of 93 SCI patients with neurogenic detrusor overactivity (NDO) treated with intravesical English BTX-A only. They were 63 males and 30 females, mean age was 37.5 years (range 20-71). Neurological lesion degree according to the ASIA scale are reported in table 1. Lesion level were as follows: 17 (18.2%) cervical, 65 (69.8%) dorsal, and 11 (11.8%) lumbar. All patients have a NDO refractory to anticholinergic therapy and use intermittent catheterizzation (IC). We administered oxybutynin 5 mg tablet 3 times/day, gradually reducing the dosage until total suspension in the third week post-injection. We injected, with a 17 Ch cystoscope and a 23 G needle-tipped catheter (5 Fr), in 20-30 sites into detrusor muscle, trigone-sparing, 20 minutes after intravesical instillation of 40 ml of lidocaine 2%. The dosages were 500, 750, 1000 U.I. diluited in 10-20 ml of saline solution. Bladder diary was cecked pre-treatment and during follow up. Videourodynamic and ultrasound evaluation were performed before and after each treatment. Re-injections were planned at recurrence of urinary incontinence previous urodynamic assessment.

N. Pts. (%) ASIA 74 (79.5) A 10 (10.7) B 4 (4.3) C 4 (4.3) D 1 (1,0) E

Table 1: Patients’ stratification according to ASIA scale. Results In all patients, we recorded an average improvement of bladder capacity of 210.5 ml (range 180-420) at least for a period of 4 months but four cases needed re-injection from 1 to 3 months after the last BTX-A treatment. Urodynamic evaluation showed a significant decrease in mean maximum detrusor pressure from 60 to 20 cmH2O. A total of 165 treatments were performed: number of treatments for each patient from 1 to

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5, mean dosage, and mean duration time are reported in table 2. In one patient, not listed in table, we perform 7 treatments. In this caseload series 5 (5.3%) patients referred hypostenia with reduced supralesional muscle force. Hypostenia disappeared from 2 to 4 weeks after injection and it depends on two main associate variables: high dosage BTX-A (1000 U.I. DysportTM) used in SCI patients with cervical complete lesion. N. Treatment N. Pts. (%) Mean Dosage U.I. (range) Mean Duration months (range) I° 93 779,5 (500-1000) - II° 44 (47,3) 748,8 (200-1000) 12 (3-40) III° 15 (34,0) 600,0 (500-1000) 13 (1-29) IV° 8 (53,3) 593,7 (500-750) 14 (5-27) V° 3 (37,5) 583,3 (500-750) 16 (5-26) Table 2. Conclusions Our study confirmed the efficacy of the DysportTM for patients with NDO using IC. We obtained a significative increased bladder capacity with detrusor pressure reduction. An important side effect is hypostenia that was no severe and it had a temporary duration not more than 1 month. The same problem may occur in patients with occulte myastenia. For this reason we tried a lower dose and this series showed to be effective avoiding side effects. Clinical, urodynamic, and duration data show no significative differences between high (1000 U.I.) and lower dosage. Patients reported subjective improvement of continence and improved quality of life. Re-injection data using DysportTM did not reveal resistant to the toxin and duration time showed a trend to be longer from the first to the last treatments. All the patients were able to suspend or reduce anticholinergic drugs. Our study confirm the efficacy of BTX-A for the treatment of NDO as reported in literature, but demonstrated particularly, the efficacy and tolerability of English BTX-A after first and repeated detrusor injection too. References Botulinum toxin-A to treat detrusor hyperreflexia in spinal cord injured patients. Neurourol Urodyn. 2001; 20: 521-522. Botulinum- A toxin in the treatment of detrusor hyperreflexia. Neurourol Urodyn. 2001; 20: 522-524. European experince of 184 cases treated with Botulinum-A toxin injections into the detrusor muscle for neurogenic incontinence. Neurourol Urodyn. 2002; 21: 427-428. 97 Haferkamp A1, Krengel U 1, Reitz A2, Grosse J3, Kramer G3, Schumacher S1, Schurch B2, Stöhrer M3, Müller S C1 1. Dept. of Urology, University of Bonn, Germany, 2. Dept. of Neurourology, Swiss Paraplegia Center, University Hospital Balgrist, Zurich, Switzerland, 3. Dept. of Urology, Berufsgenossenschaftliche Unfallklinik, Murnau, Germany ARE BOTULINUM-A TOXIN INJECTIONS INTO THE DETRUSOR OF PATIENTS WITH NEUROGENIC DETRUSOR OVERACTIVITY SAFE? ULTRASTRUCTURAL DATA OF DETRUSOR BIOPSIES. Aims of Study Schurch/Stöhrer [J. Urol. 164:692; 2000] recently introduced a new method to achieve detrusor relaxation in neurogenic detrusor overactivity by injecting 300 IU of Botulinum-A toxin endoscopically into the detrusor muscle. On average this effects lasts at least 9 months. Structural effects of Botulinum-A toxin are only known from studies on striated muscles, where a widespread nerve sprouting occurs temporarily. In addition, these injections represent microtraumas to the detrusor and may result in microscaring. The aim of this study was to evaluate the ultrastructural effects of Botulinum-A toxin injections on the human detrusor.

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Methods Detrusor biopsies were taken from 22 patients with spinal cord injury [SCI] (n=16), myelitis (n=1), idiopathic spinal cord ischemia (n=1) or meningomyelocele [MMC] (n=4). All had videourodynamically proven neurogenic detrusor overactivity (NBD). Patients were divided into two groups: Group A included 11 biopsies from patients before the first Botulinum-A toxin injection. Group B included 4 biopsies from patients within 3 months after the first injection and 7 biopsies after repeated injections (after 2 - 4 injections). The biopsies were processed by standard procedure for detailed electron microscopic study and evaluated by 2 examiners without prior knowledge of clinical/urodynamic data. They were assessed qualitatively and quantitatively for intrinsic nerve changes, especially sprouting, muscle cell fascicle structure including width of intercellular space, muscle cell junctions and amount of collagen and elastin. Results No statistically significant detrusor changes have been found concerning muscle cell fascicle structure, width of intercellular space and number and kind of muscle cell junctions. 50% to 86% of all intrinsic nerves presented with signs of degeneration in both groups. No nerve sprouting was found in group A, but it could be observed in 3 specimen from group B (p=0.214). 3 months after the botulinum-A toxin injection sprouting was observed in 0/4 biopsies, in 3/7 biopsies obtained after a mean of 8.8 months after the last injection sprouting occured (p=0.043). Specimen from group A and group B showed only limited collagen deposits within the detrusor without any statistically significant difference between the groups. Conclusions This study verifies our earlier report of severe intrinsic nerve degeneration in the human detrusor in patients with SCI or MMC. It also shows nearly no muscular structural differences of the detrusor before and after even repeated Botulinum-A toxin injections. Similar to the findings in striated muscle significant nerve sprouting occured temporarily in patients with clinically reduced effect of Botulinum-A toxin after a mean of 8.8 months after detrusor injections. 98 Spinelli M1, Malaguti S1, Giardiello G2, Lazzeri M3, Van den Hombergh U4, Gerber M5 1. Magenta Hospital, 2. Medtronic Italia, 3. Clin. S. Chiara Firenze, 4. Medtronic Europe, 5. Medtronic Inc. Mineapolis CHRONIC PUDENDAL NERVE ELECTROSTIMULATION: FIRST EXPERIENCE OF THE NEW PERCUTANEOUS IMPLANT WITH NEUROPHYSIOLOGICAL GUIDANCE Aims of Study As pudendal nerve is a one of the major nerves which innervates the pelvic floor muscles, the external urethral and anal sphincters and the pelvic organs with the anatomical possibilities to reach the nerve, one could postulate that the stimulation of this nerve could have a beneficial effect to multiple impaired functions. We decided to attempt to stimulate pudendal nerve in a chronic setting and record clinical changes. This preliminary work presents the original method for new therapeutical stimulation and minimally invasive approach to treat neurogenic patients.

Methods Pudendal nerve stimulation and the electrode placement is done during the neurophysicological monitoring using the lead and the introducer kit available for minimally invasive implant of sacral neuromodulation. Our technique consists of measuring several Pudendal Nerve Terminal Motor Latency (PNTML) responses and Compound Muscle Action potentials from external anal sphincter. The best evoked response (constituted by maximal amplitude, regular shape, shorter latency) is identified, recorded and memorized: this will be the reference potential response (RPR). The patient is placed in lithotomic position. The surgical procedure is done under local anaesthesia. An insulated needle is inserted perpendicular to the skin for about 4 cm to reach the ischial tuberosity. The needle is tilt laterally and dorsally to reach the recto-ischial fossa until it is located below and behind the ischial spine in Alcock’s channel. Once the needle is in this correct position, it is possible to place either a temporary stimulation lead (PNE) or a definitive quadripolar tined lead along the pudendal nerve in the Alcock’s channel.

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In each of the following steps the neurophysiological monitoring is repeated in order to confirm the consistency between the recorded trace and the RPR. A stylet is inserted in the needle. The introducer assembly is inserted over the stylet, the inner part of the introducer assembly is removed, the lead is inserted through the plastic sheat, the sheath is removed after the stimulation of the lead confirming the correct placement. The lead is connected to an external stimulator. An implantable pulse generator can be subcutaneously implant in case of positive results. From May 2002, 10 patients (6 male, 4 female, mean age 45, range 21-66) underwent pudendal nerve stimulation. All patients were submitted to a complete neurophysiological evaluation at baseline and were asked to fill out a bowel and voiding diary for 7 days. Baseline urodynamic assessment was performed as part of the baseline workup. All patients were neurogenic: 4 non traumatic (2 vascular myelopathy, 1 transverse myelitis, 1 syringomelia) 4 had trauma (incomplete lesion at cervical level in 2, at level D12-L1 in 1), 1 patient had peripheral lesion after pelvic surgery and 1 patient had central lesion due to cerebellum neoplasia. Main reported symptoms were: Urge incontinence in 9 and urinary retention in 1 patient. Seven patients with urge incontinence had constipation and one patient suffered from combined fecal incontinence. All patients failed conservative, 5 pts underwent SNS test stimulation (PNE) but had unsatisfactory results, 2 pts were implanted with neurostimulator (1 pt had worsening of symptoms after 6 yrs, and the other patient pts was implanted 12 months ago with only 30% of improvement). 3 pts didn’t undergo neuromodulation before pudendal stimulation. Nine out of 10 patients, were screened with a temporary stimulation (PNE) lead left in situ for at least 7 days (range 7-10). One was screened with the definitive quadripolar tined lead. Results Four out of 9 pts with urge incontinence became continent during screening phase, 1 pt improved by more 88% (from 9 to 1 daily incontinence episodes), 1 pt is still in screening phase, 3 didn’t improve. Out of the 7 patients with constipation at baseline, 5 pts reported normalization of bowel habits, 1 pt is in screening phase, 1 didn’t improve. One patient with chronic urinary retention is in screening phase. Out of 9 patients who underwent temporary pudendal nerve stimulation, 6 were selected for permanent implant and 3 pts are in currently in the screening phase. One pt who received a permanent implant was explanted one month later because of erosion of the skin at the level of the connection between lead and extension cable. Conclusions Chronic pudendal nerve stimulation is feasible, the implant of the lead is easy to perform using percutaneous technique originally developed for sacral neurostimulation. Neurophysiological guidance allows reproducible and reliable guide to place the lead. This technique could wide the field of application of electrical stimulation for treating functional disorders in neurogenic patients. Further study must carried out to identify the best selection criteria, the best stimulation parameter and to verify the long term results. 99 Bycroft J1, Bywater H2, Knight S3, Hamid R2, Shah J1, Craggs M 3 1. Institute of Urology & Nephrology, 2. Spinal Injuries Unit, Stanmore, 3. Spinal Research Centre, Stanmore VARIATION IN THE UROLOGICAL MANAGEMENT OF SPINAL CORD INJURY PATIENTS IN THE UK AND EIRE Aims of Study Spinal cord injury (SCI) is associated with a high incidence of urinary tract morbidity [1], and despite recent advances in care, the associated mortality is still much greater than that seen in the non-SCI population[2]. Despite the close relationship between SCI and urinary tract dysfunction, few guidelines are available relating to their common management. It was therefore the authors’ opinion that a great variation with regard to urological management of SCI patients existed in U.K. and Eire. To test this hypothesis, we questioned the 12 units on key areas of practice.

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Methods During December 2002, each of the 12 spinal injuries units (SIU) were sent a questionnaire relating to four main areas: urological outpatient follow-up practice, urinary tract infection (UTI) management, upper tract surveillance and urodynamic testing. The questionnaire was sent to the urologist or physician who primarily dealt with the urological aspects of patient care. Results All 12 of the units (100%) eventually replied, however 3 units had to be contacted a second time. The frequency of urological follow-up is listed in Table 1: Table 1 Frequency of routine urological outpatient follow-up in individual spinal injury units. Frequency of follow-up Number of units Only as required 2

Every 6 months 1 Annually 6 1 – 2 yearly 1 1 – 5 yearly 1 Annually; biannually if stable or >10 years since injury 1 Regarding the management of UTI, only 5 (42%) had unified department protocols. Only 1 unit would routinely treat asymptomatic UTI (in patients with permanent catheters). Of the 12 units, 4 (33%) advocated antibiotic prophylaxis for recurrent UTI. The mean duration of treatment for symptomatic UTI was 6.3 days (range 3-14). All units practiced routine upper tract monitoring with imaging studies, however there was a wide range in frequency of studies (Table 2). Table 2 Frequency of upper tract surveillance in spinal injury units. Frequency of study Number of units Annually 9 Every 18 months 1 Biannually 1 Every 3 years 1 Concerning urodynamic studies, 6 units (50%) did not perform them on a routine basis (Table 3). 3 (25%)of the units performed annual tests, however 1 of these switched to testing every 2 years if patients were ‘stable’, or greater than 10 years had passed since injury. 2 units investigated their ‘reflex voiders’ more frequently. The remaining unit performed routine urodynamics only once on patients (during rehabilitation). Table 3 Frequency of routine urodynamic studies in spinal injury units. Frequency of study Number of units Only as required or indicated 6 Only once in rehabilitation 1 Annually 1 Annually; biannually if stable or >10 years since injury 1

After 3 months, then annually 1 Only in ‘reflex voiders’ (2-3 yearly) 1 Annually in ‘reflex voiders’,

3 yearly in others 1

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Conclusions The overriding aim of the urological care of SCI patients is to prevent renal deterioration, and with appropriate surveillance and management, the morbidity and mortality from urinary tract dysfunction can be successfully prevented [3]. However, we have highlighted a current wide variation in practice in the U.K. and Eire. In relation to urological outpatient follow-up frequency, 6 (50%) of units did not perform routine review. However, some units performed annual review. Whether or not this is advantageous to patient is unknown, but these figures highlight an imbalance of care throughout the country. It is known that comprehensive outpatient care is associated with better outcomes in SCI [4]. Given the importance of the subject in SCI, it is perhaps surprising that 7 units (58%) do not have department protocols relating to UTI management. Antibiotic use in asymptomatic UTI remains contentious; where antibiotics are indicated there appears to be a wide range in treatment durations between units. Additionally, a third of units use antibiotic prophylaxis against recurrent UTI. This is again a debatable issue, as prophylaxis may in fact be harmful to patients [5]. Routine imaging is vital in the diagnosis of impending or silent pathology [6], and all units perform this (albeit at differing time intervals). Routine urodynamic studies also help to detect and manage problems, however only 50% of units perform them. In conclusion, the wide variation in urological practice in SCI highlights the need for increased research and collaboration between units to determine the best follow-up strategies. References 1 Van Kerrebroeck PE et al. Paraplegia 1993: 31(5):320-329. 2 Soden RJ et al. Spinal Cord 2000: 38(10):604-610. 3 Burns AS, Rivas DA, Ditunno JF. Spine 2001: 26(24 Suppl):S129-S136. 4 Dunn M, Love L, Ravesloot C. Spinal Cord 2000: 38(2):84-91. 5 Sandock DS, Gothe BG, Bodner DR. Paraplegia 1995: 33(3):156-160. 6 Bodley R. Eur J Radiol 2002: 42(2):135-153. 100 Sakakibara R1, Odaka T2, Uchiyama T1, Asahina M1, Yamanishi T3, Hattori T1 1. Neurology Department Chiba University, 2. 1st Internal Medicine Chiba University, 3. Urology Dokkyo Medical College DEFECATORY FUNCTION IN MULTIPLE SYSTEM ATROPHY; A COLONIC TRANSIT TIME AND VIDEOMANOMETRY STUDY Aims of Study Constipation is a prominent lower gastrointestinal tract dysfunction that occurs frequently in multiple system atrophy (MSA) (also known as Shy-Drager syndrome). We investigated colonic transport and dynamic rectoanal behaviour during filling and defecation in patients with MSA. Methods Colonic transit time (CTT) and rectoanal videomanometry analyses were performed in 15 patients with MSA (10 men and 5 women; mean age, 63.5 years; mean duration of disease, 3 years; decreased stool frequency (< 3 times a week) in 9, difficulty in stool expulsion in 11) and 10 age-matched normal control subjects (7 men and 3 women; mean age, 62 years; decreased stool frequency in 2, difficulty in stool expulsion in 2). Results In the MSA patients, CTT was significantly prolonged in the rectosigmoid segment (p<0.05) and total colon (p<0.05) compared to the control subjects. At the resting state, anal closure pressure of MSA patients were lower than that in control subjects, though not statistically significant. However, anal squeeze pressure of the patients was significantly lower than that in control subjects (p<0.01) and external sphincter EMG of the patients showed denervation motor unit potentials. MSA patients showed a smaller increase in abdominal pressure on coughing (p<0.01) and straining (not significant). During filling, MSA patients showed normal rectal volumes at first sensation and maximum desire to defecate, and normal rectal compliance. However,

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they showed smaller amplitude in phasic rectal contraction (p<0.01), which was accompanied by an increase in anal pressure that normally decreased, together with leaking in three patients. During defecation, most MSA patients could not defecate completely with larger post-defecation residuals (p<0.05). MSA patients had weak abdominal strain, smaller rectal contraction on defecation and larger anal contraction on defecation (paradoxical sphincter contraction on defecation: PSD) than those in control subjects, though these differences were not statistically significant. Conclusions Slow colonic transit, decreased phasic rectal contraction, weak abdominal strain and PSD were all features in our MSA patients with frequent constipation. Sphincter weakness as a cause of fecal incontinence is also prominent in this disorder.

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Figure 3 Results of videomanometry – rectal filling. References Iscoe S. Control of abdominal muscles. Progress in Neurobiology 1998; 56: 433-506. Kamm MA. Pelvic floor tests. Chapter 17. In: Constipation, Kamm MA, Lennard-Jones JE eds. Wrightson Biomedical Publishing, Petersfield, 1994, 145-153. Mathers SE, Kempster PA, Swash M, Lees AJ. Constipation and paradoxical puborectalis contraction in anismus and Parkinson’s disease; a dystonic phenomenon? J Neurol Neurosurg Psychiatry 1988; 51: 503-507. Mathias CJ. Gastrointestinal dysfunction in multiple system atrophy. Seminars in Neurology 1996; 16: 251-258. Stocchi F, Badiali D, Vacca L,Dlba L, Bracci F, Ruggieri S, Torti M, Berardelli A, Corazziari E. Anorectal function in multiple system atrophy and Parkinson’s disease. Mov Disord 2000; 15: 71-76. Sakakibara R, Odaka T, Uchiyama T, Asahina M, Yamaguchi K, Yamaguchi T, Yamanishi T, Hattori T. Colonic transit time and rectoanal videomanometry in Parkinson’s disease. J Neurol Neurosurg Psychiatry 2003, 74: 268-272. Sarna SK. Physiology and pathophysiology of colonic motor activity (Part one of two). Digestive Disease and Sciences 1991; 36: 827-862. 101 Laborda E1, Gelman W1, Anthony F2, Monga A1 1. Princess Anne Hospital, 2. Southampton University IS INCREASED COLLAGEN METABOLISM THE CAUSE OR EFFECT OF PROLAPSE?: A CONTROLLED STUDY Aims of Study There is a 11.7% risk during a lifetime of having at least one operation for genital prolapse (1). Risk factors include childbirth, ageing, menopause and connective tissue disorders (2). Collagen metabolism is altered in the vaginal skin of women with genitourinary prolapse. Jackson et al. (3), showed a significant reduction in the collagen content and increase in the matrix metalloproteinases (MMP2 and MMP9), suggesting an up regulation of collagen breakdown and remodelling. He postulated this as a cause of prolapse but did not prove wether this is cause or effect. The aim of this study was to compare collagen metabolism by measuring MMP2 expression in stretched and non-stretched vaginal tissue from women with prolapse allowing them to be their own controls. This would allow us answer the question of cause and effect.

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Methods Based on previous tissue studies a minimum of 9 patients was required to allow a 90% power calculation to detect a difference at 0.05 significance level. Eleven women presenting with vaginal prolapse repair were included in the study after ethical committee approval and informed consent. Patients were booked for cystocele and/or rectocele repair. Tissue samples were obtained at the time of surgery and immediately stored in liquid nitrogen until required for assay. Two samples from the same vaginal wall were obtained for each woman. One was obtained from the excised redundant vaginal skin after plication of the fascia, while the second sample was obtained from tissue proximal to the area repaired but not affected by the prolapse. The latter skin had not been stretched by the prolapsing organ and still contained the folds of normal vaginal skin. Samples were thus divided into two appropriate groups, ‘stretched’ and ‘non-stretched’ skin. Tissue samples were homogenised and homogenates were assayed for total protein and MMP2. MMP2 was measured by enzyme immunoassay using a Biotrak MMP2, human, ELISA system kit (Amersham Pharmacia Biotech). This assay recognises the precursor of MMP2 (pro-MMP2), i.e. free pro-MMP2 and that complexed with TIMP2. InStat was used to perform t test and linear regression analysis.

Results The eleven women had a mean age of 58 years old. We found when compared all samples a significant increase (p = 0.02) in the MMP2 per unit weight in the ‘stretched’ tissue compared with the matched ‘non-stretched’ tissue.However there was no significant diference (p=0.92) on the MMP2 per unit of protein in both groups. In addition, there was a correlation (p= 0.02) between the amount of MMP2 per unit of protein in the ‘stretched‘ tissue compared with the ‘non-stretched’ tissue of the same women. Paired t test stretched non-stretched p value weight 29.18 29.81 p= 0.57 MMP2/weight 0.15 0.11 p= 0.02 MMP2/prot 19.69 19.82 p= 0.92 Linear regression stretched non-stretched p value MMP2/prot 19.69 19.82 p= 0.02 Conclusions 1. There is a significant increase in MMP2 production in ‘stretched’ vaginal tissue compared with that which had not undergone any stretching in the same women with vaginal prolapse. That would suggest stretching cuases up regulation. 2. In addition, however, a correlation between MMP2 per unit protein from the stretched tissue matched with the non-stretched of the same women was still seen. This could suggest some inherent factor within the tissue (may be inherited ) that leads to up regulation in women with prolapse. References (1) Olsen AL, Smith VJ, Bergstrom JO, Collins JC, Clark AL. Epidemiology of surgically managed pelvic organ prolapse and urinary incontinence. Obstet Gynecol 1997; 89:501-6. (2) Norton PA, Baker JE, Sharp HC, Warenski JC. Genitourinary prolapse and joint hypermobility in women. Obstet Gynecol 1995; 85:225-8. (3) Jackson SR , Avery NC, Tarlton JF, Eckford SD, Abrams P, Bailey AJ. Changes in metabolism of collagen in genitourinary prolapse. Lancet 1996; 347: 1658-61.

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102 Chaliha C 1, Khullar V1, Sultan A2, Monga A3, Stanton S L4 1. Imperial College, St Mary's Hospital, 2. Mayday University Hospital, 3. Southampton General Hospital, 4. St George's Hospital, London URETHRAL FUNCTION FOLLOWING VAGINAL OR CESAREAN DELIVERY. Aims of Study Vaginal delivery is implicated as a significant aetiological factor in the development of urinary incontinence. However though the prevalence of urinary incontinence is as high as 35% after delivery ,1 the pathophysiology is still unclear. Pelvic floor denervation reported in 80% after vaginal delivery but recovers in 60% at 2 months postpartum.2 Urethral support defects noted in 50% after vaginal delivery lead to alterations in bladder neck position & ability to contract the pelvic floor.3 However neither of these studies correlated symptoms with pelvic floor damage. Cystometry in pregnancy and postpartum also does not explain the high prevalence of urinary symptoms.4 Pressure-flow studies have been used to assess urethral resistance.5 Using this method the parameters which can be measured are the detrusor pressure pressure as urinary flow commences urethral opening pressure (UOP), detrusor pressure at the end of voiding, urethral closure pressure (UCP). Women with urodynamic stress incontinence have lower opening and closure pressures than women with competent urethral sphincters. The aim of our study was to evaluate the effect of childbirth on urethral resistance using pressure flow analysis and to determine the relationship of this pressure flow data to urinary incontinence. Methods

This was a prospective longitudinal study in a London teaching hospital. All nulliparous women in their first pregnancy were invited to participate. Exclusion criteria included pre-existing diabetes mellitus, neurological disorders, a history of urinary tract surgery, anatomical abnormalities of the urinary tract and active urinary tract infection. The investigations included a urinary symptom questionnaire with questions about urgency, stress and urge incontinence and then twin-channel subtracted cystometry was performed with a pressure-flow study at the end of the procedure. These investigations were performed in the third trimester & 12 weeks postpartum. Results 39 women had complete pressure flow data before and after childbirth. The average age was 29 years ( range 18-39) and average gestational age at 1st visit – 36 weeks ( range 34-39). Thirty women delivered vaginally (6 had an instrumental delivery) and 9 underwent a Caesarean section (3 pre-labour). All women were continent prior to pregnancy. During pregnancy 17(46%) reported stress incontinence and postpartum 10(26%) reported stress incontinence. The UOP and UCP before and after delivery are shown in Table One. There was a statistically significant reduction in UOP in women who delivered vaginally (p<0.05) compared to caesarean section but no significant changes in UCP.

There was no relationship between UOP &UCP in pregnancy & postpartum and the symptom of stress incontinence.

Table One -UOP and UCP before and delivery according to mode of delivery. Antenatal Postnatal Vaginal delivery UOP (n=30) UCP

37 (19) 30 (21)

23 (27)* 24 (29)

Caesarean section UOP (n=9) UCP

29 (29) 27 (31)

28 (19) 26 (22)

UOP = urethral opening pressure (cmH20) UCP = urethral closure pressure (cmH20) *p=<0.05, All data presented as mean values (standard deviation).

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Table 2. UOP and UCP before and after delivery in women reporting stress incontinence compared to asymptomatic women.

Detrusor opening pressure* Antenatal Postnatal

Detrusor closure pressure* Antenatal Postnatal

Asymptomatic 35(19) (n=22)

41(14) (n=10)

30(23) (n=22)

46(17) (n=10)

Symptomatic 35 (25) (n=17)

33 (24) (n=29)

30(25) (n=17)

28(25) (n=29)

*cmH2O All data presented as means (standard deviation) Conclusions This is the first study to demonstrate a reduction in urethral resistance after vaginal delivery compared to Caesarean section. This suggests that vaginal delivery damages the urethral sphincter mechanism. The lack of relationship between urethral opening and closure pressures and symptoms may be because of the small size of this study, but more likely as the symptom of stress incontinence may reflect both underlying detrusor overactivity or urodynamic stress incontinence. A larger study, with long-term follow-up is required to assess if these changes in urethral sphincter function are associated with the subsequent development of urinary incontinence. This again raises the question of promoting elective Caesarean section to protect the urinary continence mechanism. References 1.Wilson PD, Herbison RM, Herbison GP. Br J Obstet Gynaecol 1996;103:154-161.

2. Snooks et al. Lancet 1984 ;ii:546-550. 3. Peschers U et al. Obstet Gynecol 1996;88:1001-6. 4. Chaliha C et al. Br J Obstet Gynaecol 2000;107:1354-59.

5. Wagg AS et al. .J Urol 1996;1984-1988. 103 Barber M1, Walters M1, Bump R 2 1. Cleveland Clinic Foundation, 2. Lilly Research Labs ASSOCIATION OF THE MAGNITUDE OF PELVIC ORGAN PROLAPSE AND PRESENCE AND SEVERITY OF SYMPTOMS Aims of Study To determine the relationship between magnitude of pelvic organ prolapse (POP) and the presence and severity of bowel, bladder and vaginal symptoms. Methods One hundred and sixty-two women who were recruited at 2 different medical centers for one of three studies validating the Pelvic Floor Distress Inventory (PFDI) and Pelvic Floor Impact Questionnaire (PFIQ) are the subject of this study.[1] All subjects presented with one or more pelvic floor symptoms. Each underwent a comprehensive urogynecologic evaluation including pelvic examination using the Pelvic Organ Prolapse Quantitation system (POPQ) and completed the PFDI, a validated self-administered condition specific quality of life instrument for women with pelvic floor disorders. The PFDI assesses the presence of a variety of bowel, bladder and pelvic symptoms and the degree of bother caused by these symptoms on a four-point scale from 1 = not at all to 4 = quite a bit. The presence of and degree of bother caused by symptoms was correlated with the extent of anterior, posterior and maximal POP using Spearman’s correlation coefficient. The prevalence of each symptom was determined for each 1 cm increment of POP (measured in reference to the hymen) in order to identify any “threshold” where symptoms begin to develop/resolve. Statistical analysis was performed with SAS v. 9.0 (SAS Institute, Cary, NC)

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Results The mean age of subjects was 53 years (range 22-86). The distribution of POP stage was 20% Stage 0, 25% Stage 1, 23% Stage 2, 26% Stage 3 and 6% Stage 4. Prolapse symptoms such as a sensation of bulging or protrusion, feeling pelvic heaviness or dullness, or visualizing a bulge all correlated weakly to moderately with increasing POP (r = .56, .26, and .53 respectively, p<.0001). The degree of bother caused by these symptoms also increased significantly with worsening POP (p<.0001). There was a dramatic increase in the proportion of patients who noted that they could see or feel a vaginal bulge when the maximum extent of POP extended beyond the hymen (11% when maximum prolapse less than 1 cm above hymen, 41% at hymen and 93% 1 cm or greater beyond hymen). In contrast, the proportion with a sensation of bulging or a feeling of heaviness increased gradually as the maximal extent of POP proceeded from normal support to advanced POP. Neither symptoms of pelvic pressure nor pain correlated with POP severity. The presence of bladder symptoms such as difficulty emptying, incomplete emptying, frequency and urgency did not correlate with the degree of anterior vaginal prolapse, however the degree of bother caused by these symptoms was weakly related to increasing POP (r = .19 to .23, p<.02 for each). Three percent of subjects (4/108) whose anterior prolapse was above the hymen complained of splinting to urinate compared with 36% (15/42) of those prolapse protruded 1cm or more beyond the hymen. The proportion of subjects complaining of stress urinary incontinence increased steadily from 31% (18/55) for those with normal anterior support to 100% (13/13) for those with prolapse to the level of the hymen, then suddenly decreased as the prolapse extended 1cm or greater beyond the hymen (41%; 15/37). Fecal incontinence, hard straining and feeling of incomplete emptying did not correlate with severity of posterior vaginal prolapse, however splinting to complete bowel movements did (r = .33, p<.0001). Conclusions Symptoms such as bulging, heaviness and splinting to urinate or defecate correlate with increasing severity of pelvic organ prolapse, however many bowel or bladder symptoms typically attributed to prolapse do not. References 1. Psychometric Evaluation of two Comprehensive Condition-Specific Quality of Life Instruments for Women with Pelvic Floor Disorders. Am J Obstet Gynecol 2001; 185(6):1388-95. 104 Buchsbaum G1, Kerr L2, Guzick D1 1. University of Rochester, 2. Burlington, Vermont PELVIC RELAXATION IN NULLIPAROUS POSTMENOPAUSAL WOMEN AND THEIR PAROUS SISTERS. Aims of Study To compare pelvic floor relaxation in postmenopausal nulliparous women and their parous sisters, in order to determine the importance of vaginal delivery in the development of pelvic relaxation disorders. Methods We used a matched-pair design to address these questions regarding risk factors for pelvic organ prolapse in postmenopausal women. Nulliparous postmenopausal women, who lacked the key risk factor under study (vaginal delivery), were paired with their biological sisters who had at least one vaginal delivery. Both members of the sister pair completed a study survey. The survey included questions about the presence of symptoms related to urinary incontinence and pelvic organ prolapse, a social impact questionnaire and questions inquiring about past medical and surgical history and medications. Study participants then underwent a clinical assessment for pelvic support. Findings on pelvic exams were recorded. Chi square analysis was used to evaluate the data for statistical significance. At the initial exam, the examiner was blinded to answers to the survey, unaware of parity of the subject and symptoms of UI or POP. In evaluation of the data, descriptive tabulations are presented of relevant demographic and clinical variables for the nulliparous women and their parous sisters. The internal review board of the University of Rochester has approved this study.

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Results A total of 27 sister pairs are reported on in this study. The mean parity is 3.7 (SD 2.2) in the parous sister group. There are no statistically significant differences in demographic variables between the nulliparous and the parous group. Support of anterior vaginal wall, posterior wall and apex are compared. The majority of sister pairs are found to have identical staging of the anterior wall and the apex. Only two sister pairs (7.4%) differed by two stages in relaxation of anterior vaginal wall and apex respectively (p= .69). On the other hand, when comparing relaxation of the posterior vaginal wall 7 pairs (25.9%) differed by two or more stages (p= .065). In six of the seven pairs the parous sister had the higher staged rectocele. There was no correlation between continence status and finding of pelvic relaxation on physical exam. Conclusions Damage to the pelvic floor at time of vaginal delivery is regarded as the primary risk factor for pelvic floor relaxation. Our findings do not support this general assumption. The concordance of pelvic support of the anterior vaginal wall and apex between sister-pairs is striking. This might suggest a familial predisposition for pelvic relaxation disorders. Only in the posterior compartment did the difference in exams approach significance, which potentially could be the sequelae of trauma at time of vaginal delivery. 105 Miller J M1, Umek W H1, DeLancey J1, Ashton-Miller J A1 1. University of Michigan PUBOCOCCYGEAL MUSCLE INTEGRITY AND URETHRAL CLOSURE PRESSURES DURING VOLITIONAL PELVIC FLOOR MUSCLE CONTRACTION IN WOMEN WITHOUT STRESS INCONTINENCE OR PELVIC ORGAN PROLAPSE Aims of the study An increase of urethral closure pressure during volitional pelvic floor muscle contraction could arise from activity of the striated urogenital sphincter, the pubococcygeal portion of the levator ani muscle, or both. This study was undertaken to determine the degree to which complete loss of the pubococcygeal muscle affected women’s ability to volitionally augment their urethral closure pressures by using a volitional pelvic floor muscle contraction (“Kegel effort”). Methods The sample consisted of a subset of women who volunteered as healthy controls in a larger IRB-approved study. They were free of urinary leakage or prolapse and had a negative stress test. Multiplanar proton density MR images of the pelvis were obtained in all women. A trained observer evaluated each scan to determine pubococcygeal muscle status. Women were selected for analysis if they demonstrated either intact puboccygeus muscle (n=28, mean age: 54 years) or absent pubococcygeal muscle (n=17, mean age: 59 years). Women with partial defects (e.g. one-sided only) were excluded. The Figure shows example MRI scans portraying intact (left picture) and absent (right picture) pubococcygeal muscles. Urethral pressures were obtained in cm H2O using an 8 Fr. Microtip transducer (GaeltecTM, Medical Measurements Inc., Hackensack, NJ, USA). Maximal urethral closure pressures (MUCP) were measured with women at rest while the catheter was pulled through the urethra. Women were then asked to perform two to three Kegel efforts while the transducer was held at the point of MUCP. Outcome variables were the mean changes in individual’s urethral closure pressures produced by the Kegel efforts and the percentage of women in each group who were able to increase their MUCP by more than 5 cm H2O. Group comparisons were made using descriptive statistics and Student’s T-test.

510

PC Intact (n=28)

15

50

85

120

Rest Kegel

PC Absent (n=17)

15

50

85

120

Rest Kegel

Results Differences between groups regarding age or resting MUCP were not statistically different. In the graph at right each woman’s pressure at rest and during pelvic floor muscle contraction (Kegel) are shown connected by a line. Some women in both groups were able to increase urethral closure pressure from the resting value by using a Kegel effort. Women without pubococcygeal muscles (“PC Absent”) were about half as likely to be able to increase pressure by more than 5 cm H2O (see table). Moreover, their mean pressure increases were 43% lower than in women with intact muscles (p = .015). Conclusion Women with an absent pubococcygeal muscle are only half as likely to be able to increase their urethral closure pressure more than 5 cm H2O and generate 43% less pressure with pelvic muscle contraction as women with normal women. Comment: The increase in urethral closure pressure in women without pubococcygeal muscle would be primarily attributable to the urogenital sphincter. We gratefully acknowledge NIH support: R01 NICHD 01-38665-03. 106 Morgan D1, Fenner D1, Wolfgang U1, Guire K 1, DeLancey J 1 1. University of Michigan STRESS URINARY INCONTINENCE, URETHRAL SUPPORT, AND URETHRAL FUNCTION AMONG WOMEN WITH PELVIC ORGAN PROLAPSE ANALYZED BY PROLAPSE TYPE Aims of Study To evaluate 1) the occurrence of stress urinary incontinence (SUI) and 2) the status of urethral support and function in women with untreated pelvic organ prolapse grouped by most dependent compartment.

Methods Women with untreated (primary) pelvic organ prolapse at least one centimeter below the hymen were enrolled as part of an IRB approved study. Women with a history of surgery for prolapse were excluded from the study. Patients completed the incontinence screening questionnaire (ISQ) [1] and underwent an examination which included pelvic organ prolapse quantification (POP-Q) [2] examination, Q-tip testing, and a urethral pressure profile (UPP). With the exception of the UPP, examinations were done without elevation of the prolapse. Demonstrable incontinence was assessed in the standing position with 250 cc in the bladder. Groupings into anterior, apical, and posterior prolapse were determined by the most dependent

PC Intact PC Absent Pressure Increase > 5 cm H2O

86% 41%

Mean MUCP (SD) 58 (21) 55 (19) Mean Pressure Rise (SD) 14 (11) 6 (9)

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part of the vaginal wall or cervix found by POP-Q. The apex was the cervix when the uterus was in situ or the vaginal scar status post hysterectomy. Urethral support was assessed during pelvic examination by the Q-tip angle when resting, contracting the pelvic floor muscles, and straining. Maximum urethral closure pressure (MUCP) was determined with a UPP. The data regarding demonstration of SUI in the standing position were analyzed using a chi square test. Q-tip angle measures and MUCP were compared using a one way analysis of variance with post hoc pairwise comparisons. Results 102 women with primary pelvic organ prolapse were enrolled. Mean age (± SD) was 57.1 ± 12.5 years; mean parity was 3.1 ± 1.8; and mean body mass index was 26.0 ± 5.0 kg/m2. The dependent site of prolapse was the anterior, apical and posterior compartments in 62.7% (n=64), 21.6% (n=22), and 15.7% (n=16) of women respectively. There were 26 of the 102 cases that had had a hysterectomy. Women that had undergone hysterectomy had the same distribution of the dependent point of the prolapse as those with a uterus in situ. The mean position (± SD) of the leading point of the anterior, apical and posterior compartments in these groups were respectively 2.3 ± 1.4cm, 4.0 ± 2.5cm, 1.9 ± 1.5cm below the hymen. 30% reported that they had leaked on “at least half of the occasions” in the past month when they “coughed, laughed, or sneezed.” 24.2% objectively demonstrated SUI. When analyzed by prolapse type, women in the posterior group were more likely to demonstrate SUI and had better resting urethral support than those in the anterior and apical groups. In addition, women in the posterior group were better able to elevate the urethra during a pelvic muscle contraction than were those in the anterior group. No statistical difference was noted in urethral function by the urethral pressure profile. The table below provides analysis of parameters with respect to type of prolapse.

Type of prolapse Examination

Anterior (n=64)

Apical (n=22)

Posterior (n=16)

Statistical Significance

% reporting SUI 27 30 41 NS % demonstrating SUI on examination

19 18 56 Ant v Apical: NS Ant v Post: p=.004 Apical v. Post: p=.014

Q-tip angle (degrees) Mean Resting ± SD 16 ± 21 17 ± 22 2 ± 17 Ant v Apical:p=NS

Ant v Post: p=.02 Apical v Post p=.03

Contracting pelvic floor ± SD

8 ± 27 2.5 ± 30 -11 ± 25 Ant v. Apical p=NS Ant v Post p=.01 Apical v Post p=NS

Straining ± SD 47 ± 28 38 ± 27 38 ± 21 NS Maximum Urethral Closure Pressure (cmH2O) ± SD

65 ± 34 71 ± 37 53 ± 25 NS

NS: not significant Conclusions Stress urinary incontinence was objectively demonstrated in 24% of women with pelvic organ prolapse. Unexpectedly, those women with a posterior prolapse were more likely to demonstrate SUI than were women with anterior or apical prolapse despite better urethral support. We gratefully acknowledge support from the NIH: R01 NICHD 01-38665-03 References 1. Gunthorpe W, Brown W, and Redman S. The Development and Evaluation of an Incontinence Screening Questionnaire for Female Primary Care. Neurourology and Urodynamics 2000;19:595-607. 2. Bump RC, Mattiasson A, Bo K, Brubaker LP, DeLancey JOL, Klarskov P, Shull B, and Smith ARB. The Standardization of Terminology of Female Pelvic Organ Prolapse and Pelvic Floor Dysfunction. American Journal of Obstetrics and Gynecology 1996;175:10-17.

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107 Ghetti C1, Gregory T1, Edwards R1, Clark A1 1. Oregon Health and Science University SEVERITY OF PELVIC ORGAN PROLAPSE IS ASSOCIATED WITH MEASUREMENTS OF GENITAL HIATUS Aims of Study Berglas and Rubin radiographically demonstrated enlarged levator hiatuses in women with severe pelvic organ prolapse [1]. Prior to the standard use of the Pelvic Organ Prolapse Quantification (POPQ) system, Delancey and Hurd investigated the relationship between degree of prolapse and genital hiatus area [2]. The present study aims to evaluate the relationship between the severity of pelvic organ prolapse and two clinical measurements of genital hiatus. Methods We studied all patients referred to an academic Urogynecologic practice for initial evaluation between January 1997 and December 2002. Physical exam findings were prospectively entered into a database at the time of evaluation. The severity of pelvic organ prolapse was defined using both ordinal staging and the lowest overall POPQ measurement. Methods, definitions, and descriptions conform to the standards recommended by the International Continence Society [3]. For all patients, the introital hiatus was defined as the POPQ measurement for genital hiatus (gh). For a subset of patients, separate measurements of the levator hiatus were obtained in the transverse and longitudinal dimensions by palpation of the muscle borders at maximal contraction. Pearson and Kendall’s tau-b correlations were calculated. Results One thousand thirty seven patients had complete POPQ measurements. The mean patient age was 56.7±14.4 years, and the mean parity was 2.8 ±1.5. Seventy seven percent of patients had a Stage 2 prolapse or greater. Stage was positively correlated with gh (r=0.4, p<.0001). Lowest POPQ measurement correlated with gh as shown in the Figure 1. Figure 1: Correlation between lowest POPQ measurement and gh measurement.

Three hundred eight seven patients had separate measurements of the levator hiatus. In this subset, measurements of levator hiatus were positively correlated with lowest POPQ measurement (transverse

gh (cm)

1086420

low

est P

OPQ

mea

sure

men

t (cm

)

12

10

8

6

4

2

0

-2-4

r=.5r2=.25p<.0001

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r=0.4, p<.0001; longitudinal r=0.5, p<.0001). Both measurements of levator hiatus were also positively correlated with gh (r=0.5, p <.0001). Conclusions This study demonstrates that increased severity of prolapse is associated with both an enlarged introital and levator muscle hiatus. The POPQ measurement gh is an easily obtained indicator of levator hiatus size. References 1. Berglas B, Rubin IC (1953) Study of the supportive structures of the uterus by levator myography. Surg Gynecol Obstet 97: 677-92. 2. Delancey JO, Hurd W (1998) Size of the urogenital hiatus in the levator ani muscles in normal women and women with pelvic organ prolapse. Obstet Gynecol. 91: 364-8. 3. Bump RC, etal. (1996) The standardization of terminology of female pelvic organ prolapse and pelvic floor dysfunction. Am J Obstet Gynecol 175:10-17. 108 Morin M1, Dumoulin C1, Bourbonnais D1, Lemieux M1, Gravel D1 1. University of Montreal DYNAMOMETRIC EVALUATION OF PELVIC FLOOR MUSCLES FUNCTION IN CONTINENT AND STRESS URINARY INCONTINENT WOMEN Aims of Study It has been hypothesized that a strong, fast pelvic floor muscles (PFM) contraction helps to clamp the urethra, thus preventing urinary leakage during abrupt increases in intra-abdominal pressure [1]. Moreover, it has been suggested that PFM help to support the pelvic organs, allowing an optimal position of the urethra for continence [2]. Alterations in PFM seem to be associated with stress urinary incontinence (SUI). The purpose of the study was to compare the PFM function in continent and stress urinary incontinent women using an instrumented speculum [3]. Methods Eighty-nine women, 25 primipara and 64 multipara, recruited at Ste-Justine Hospital in Montreal were asked if they experienced stress urinary leakage. A 20-minute pad test was performed to confirm continence in asymtomatic women and to appreciate the severity of incontinence in women who had reported leakage. A conventional urodynamic examination was also carried out in incontinent women in order to exclude women who demonstrated uninhibited detrusor contractions. During the measurements, women adopted a supine lying position with knees and hips flexed. Information about contracting their PFM was given and their ability to contract was verified by digital assessment. A physiotherapist using an instrumented speculum carried out the assessment. This reliable instrument has the characteristic of measuring the resultant force independently of its site of application on the branch of the speculum [3]. The dynamometric assessment of the pelvic floor was conducted at minimal opening (5 mm between the two speculum branches) corresponding to the same vaginal aperture as with digital palpation. Three unrecorded practice contractions were performed to ensure that the subjects were comfortable with the device. The PFM strength was evaluated in four different conditions. 1- Women were asked to relax their PFM in order to assess the passive force (baseline value) over a period of 15 s. 2- For the maximal strength trial, subjects were instructed to contract their PFM maximally for 10 s. The subjects were not instructed by the physiotherapist about the rapidity of contraction. 3- To evaluate the speed of contraction, women were instructed to contract maximally and relax as fast as possible during 15 s. The speed of contraction was quantified by the mean rate of force change of the first contraction (slope of the force curve) and the number of contractions they performed. 4- During the endurance measurements, the subjects were asked to maintain a maximal contraction for 90 s. The area under the force curve was utilized as the endurance parameter. Maximal force values were obtained during a maximal strength trial as well as during the

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conditions evaluating the speed of contraction and endurance. The maximal force value was calculated as the peak force value during the effort minus the baseline value recorded just before the beginning of contraction. Considering the significant differences between the two groups in age (p<0.001) and parity (p<0.035) at baseline, ANCOVAs were used to control for these confounding variables. Results The pad test results corroborated with the reported continence status in all women. Thus, 30 were continent and 59 were diagnosed with SUI. The mean ages were 31.9 years (±5.5 SD) and 36.1 years (±3.6 SD) for continent and incontinent women, respectively. Continent women had a mean parity of 1.7 (±0.8 SD) while incontinent women had 2.1 (±0.8 SD). Incontinent women had urinary leakages of 35.22 g (±55.4 SD) following the standardized pad test. Table 1 shows the PFM function in continent and incontinent women. Table 1 – PFM function

Mean (SD)

Conditions Parameters

Continent SUI

Significance

Passive force Force (N) 2.3 (1.0)

1.1 (1.1)

p < 0.001

Maximal strength

Maximal force (N) 4.5 (2.3)

3.7 (1.8)

p= 0.229

Rate of force (N/s)

8.7 (4.5)

5.6 (3.9)

p= 0.012

Number of contractions (count)

10.3 (3.9)

8.5 (3.0)

p= 0.011

Speed of contraction

Maximal force (N) 4.1 (2.6)

3.0 (1.7)

p= 0.058

Endurance Endurance area under the force curve (N*s)

129.1 (75.3)

81.3 (52.8)

p= 0.001

Maximal force (N) 4.3 (2.0)

3.2 (1.6)

p= 0.028

Incontinent women demonstrated lower values in passive force, endurance (area under the curve) and speed of contraction (rate of force and number of contractions performed) than continent women (p<0.05). Differences between the two groups for maximal force reach the statistically significant level only in the endurance condition. Conclusions The PFM function is impaired in incontinent women. Our results suggest that PFM assessments should not be limited to maximal strength. Other physiological parameters of the PFM significantly distinguish between continent and incontinent women. These measurements may prove useful for evaluating the efficacy of conservative treatment and define the underlying changes in PFM function following treatment. References 1. DeLancey JOL. 1988. Structural aspect of urethrovesical function in the female. Neurourology and Urodynamics 7:509-7519. 2. DeLancey JO, Starr RA. 1990. Histology of the connection between the vagina and levator ani muscles. Implications for urinary tract function. Journal of Reproductive Medicine 35:765-71. 3.Reliability of dynamometric measurements of the pelvic floor musculature using the Montreal dynamometer. Proceedings of the 2nd International Consultation on Incontinence, 2001; Paris. p 48.

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109 Claerhout F1, Deprest J2, Zheng F3, Konstantinovic M4, Lagae P4, De Ridder D5 1. UniversityPelvic Floor Unit, Hospital Gasthuisberg, 2. Dept. Obstetrics and Gynaecology, UZ Gasthuisberg, 3. Centre for Surgical Technologies, KU Leuven, 4. Centre for Surgical Technologies, 5. Dept. Urology, UZ Gasthuisberg LONG TERM EVALUATION OF THE TISSUE RESPONSE AND MECHANICAL PROPERTIES OF TWO COLLAGEN BASED AND POLYPROPYLENE IMPLANTS IN A RABBIT MODEL FOR ABDOMINAL WALL REPAIR. Aims of Study Implant materials are often used to reinforce repairs using native fascia in prolapse patients. Polypropylene is the best studied material but clinical and experimental data on recently introduced collagen based materials remain scarse. We conducted a long term experimental study in rabbits, comparing herniation, adhesion formation and tensile strength of porcine dermal collagen (Pelvicol, Bard), collagen matrix derived from porcine small intestinal mucosa (SIS, Cook) and Prolene (Johnson&Johnson). Methods Four 2.5x2.5 cm full thickness abdominal wall defects were created in 45 rabbits. In a random fashion defects were primarily closed with the studied materials. Implants were sutured to the native tissues with Prolene 3.0. Nine rabbits were sacrificed at either 30, 60, 90, 180 or 360 days (d), at what time the presence of herniation, infection and adhesions were assessed. Tensile strength of freshly harvested explants (= implant, the interface to the recipient and surrounding native fascia) was measured with a tensiometer, noting the tearing force (N) both at the level of the interface as well as from the implant itself (frame F-DM-H1072; console TT-DM-1118; Instron Corp, Canton, MA). Results Surgisis was as such not recognisable anymore after 3 months (Figure 2); the implant area appeared at that time as a thin, nearly transparent membrane. Pelvicol remained well recognisable during the entire year following implantation, covered with a layer of 1-2 mm of connective tissue (Figure 1). One rabbit showed herniation through two of the four implant areas, i.e. a Pelvicol and a SIS reconstruction area (Figure 3). The two non involved implant areas were covered by Prolene. Adhesions were more frequent in the Prolene group than in the collagen-based implants (5.1% versus 73%; P< .05). In the latter, adhesions were mainly located on the prolene sutures at the interface. Tensiometry showed that for Prolene and Pelvicol explants, the explant always did tear at the interface (interquartile range : 10-15 N). For Surgisis explants, the implant itself ruptured first in 72% of cases. As for the materials, Prolene was always the strongest. In the first half year, Pelvicol was as strong as Prolene and stronger than Surgisis, but from 180 d on, its strength decreased gradually to levels comparable to SIS animals (table). Conclusions When Pelvicol and Prolene were used in an experimental setting, the interface between native tissues and the implant is always the weakest point. For Surgisis, in three quarters of cases the locus minoris resistentiae is the implant itself. Clinically, Prolene induces more adhesions but has the highest tensile strength over a 1-year observation period. Generally spoken Pelvicol is not degraded, while Surgisis is not recognisable within months. Despite the lower tensile strength of the collagen based materials, and clear resorption and remodelling of the SIS-implants, herniation is uncommon in both collagen based implants. There were no herniations in the Prolene group.

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110 Canepa G1, Garaventa M1, Parodi M1, Steardo L1, Satta P1, Maffenzzini M1 1. E.O.Ospedali Galliera IS THE EFFICACY OF PELVIC FLOOR MUSCLE REHABILITATION FOR URINARY STRESS INCONTINENCE AGE-RELATED? A REVISION OF 170 WOMEN. Aims of Study Pelvic floor rehabilitation is generally considered appropriate for women with mild-to-moderate stress incontinence. Female urinary incontinence affects approximately 5% of younger women to nearly 50% of elderly women. Success of pelvic floor muscle training, that is integrated on the physical therapies, depend partly on ability to perform a correct voluntary muscular contraction. Authors reported that 50% of women were unable to perform a correct voluntary pelvic floor muscular contraction following brief verbal instruction. As the presence of high body mass index, previous pelvic surgery, strong levator muscles and urethral hypermobility appeared to be poor prognostic features. So research for finding factors correlated with efficacy in conservative urinary stress incontinence is still active. Aim of the study is to evaluate if the efficacy of pelvic floor muscle is age dependent. To obtain these data we reviewed a series of 170 consecutive patients suffering from mild to moderate urinary stress incontinence.

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Methods From June 1999 to June 2002 a total of 218 women were inserted in a pelvic floor rehabilitation program for stress and urge urinary incontinence. All of them underwent a complete work-up for incontinence: anamnesis, physical and vaginal examen, urinalysis, complete urodynamic test, diary minction test. The Ingelman Sundberg scale (I.S.) was used for the classification of urinary stress incontinence. The Baden-Walker classification (HWS) was used for organ prolapse evaluation. The same procedure was applied to all the patients affected by urinary stress incontinence, consisting of 10 séances twice weekly, during which patients were subjected to physical therapy, biofeedback and vaginal electrical stimulation of 20Hz frequency. In case of urge or mixed incontinence the vaginal electrical stimulation was modified to 10 Hz frequency using the same timing for stress group. A selection of 170 patients, 54.8 + 11.1 years old (mean age + SD), ( min 33 – max 81 years old) with a mean parity of 1.6 + 0.8 deliveries, suffering from mild to moderate urinary stress incontinence were divided in two groups using, as an arbitrary cut-off, the age of fifty years old. We recall all 170 women to obtain a subjective evaluation of their continence in terms of leakage and pads used. They were classified as cured when referred no leakage, as improved or worsened in comparison with the previous incontinent condition. Results One hundred and twenty eight women were classified in Group 1 of stress incontinence, 42 belonged to Group 2 of I.S. scale. The HWS presented a minimal presence of anterior and posterior prolapse (max score was 2). Of the 170 women 113 were over fifty years old and 57 were under fifty. The mean follow-up period was 18.7 + 12 months (min 3 – max 38). In the pre-treatment evaluation 79 patients (69.9%) were classified in the 1 I.S. scale and 34 patients in the 2 I.S scale (30.1%) for the over-50 group. In the group under-50 years old 49 patients (85.9%) were in the 1 I.S. scale and 8 patients (14.1%) in 2 I.S. scale. The results demonstrated in the over-50 group that 76.1% were cured, 6.2% improved continence and 17.7% worsened. In the under-50 group 94.7% were cured and 5.3% worsened.

Conclusions The comparison of two groups of patients affected by urinary stress incontinence only separated by age seems to present a real factor of difference supporting the efficacy of rehabilitation program. It is quite obvious that in younger women the exercise of pelvic floor muscle, the attention to the biofeedback method and the major recruitment of muscular fibre by electrical stimulation are a very efficient method to cure mild-to-moderate stress incontinence. This is to confirm also that the behavioural education in young women could be a sensible and curative method. We have choosen fifty years as cut-off only on the basis of an arbitrary concept of human mean life and the beginning of menopausal period. The variation of the cut-off up or down doesn’t modify the results. Nontheless in older women the rehabilitation of the pelvic floor muscle is efficient but it depends on several negative factors all under the influence of age.

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111 Wang A1, Wang Y1 1. Chang Gung University Hospital SINGLE BLIND, RANDOMIZED TRIAL OF PELVIC FLOOR MUSCLE TRAINING (PFMT), BIOFEEDBACK ASSISSTED PELVIC FLOOR MUSCLE TRAINING (BAPFMT) AND ELECTRICAL STIMULATION (ES) IN THE MANAGEMENT OF OVERACTIVE BLADDER (OAB) Aims of Study To compare the efficacy of PFMT, BAPFMT and ES in the management of OAB in women. Methods Eligible patients had clincially proven OAB, i.e., they had the symptoms of frequency, urgency, or nocturia, with or without urge incontinence. Exclusion criteria included pregnancy, deafness, neurological disorders, diabetes mellitus, pacemaker or intrauterine device users, genital prolapse greater than stage� of the ICS grading system, residual urine �100ml, and urinary tract infection. Inclusion criteria included ages between 16-75, symptoms/signs of OAB more than 6 months, frequency of voiding � 8 / day, and urgency of voiding � 1 / day. After the calculation of sample size, which disclosed the total sample size should be at least 102 women, randomization of the eligible participants into the 3 treatment groups was performed. Initial assessment included a detailed medical history, a pelvic exam in the dorsal lithotomy position, a 1-hour pad test and a filling and voiding cystometry, as well as a 4-day 24-hour frequency/volume chart. Other assessments were comprised of evaluation of pelvic floor muscle strength using internal digital assessment according to the Oxford grading system, and measurement of vaginal pressure with a balloon probe connected to a pressure transducer, as well as the King’s Health Questionnaire. The interventions included ① a PFMT program tailored according to the subject’s PERFECT scheme, ② an EMG BAPFMT program with an intra-vaginal probeaccompanied with a home program tailored according to the subjects PERFECT scheme, and ③ an ES program using a biphasic symmetrical probe current with a frequency of 10 Hz, a pulse width of 400µs, and a duty cycle of 10/5.The treatment period consisted of 12 weeks. The PFMT program utilized the PERFECT scheme to train the patients at home. These patients also returned twice a week to the physiotherapy unit for mentoring the progress. The treatment protocol for the BAPFMT and ES groups was conducted twice a week at the physiotherapy unit. The main outcome measures were post-treatment pelvic floor muscle strength, the record of frequency/volume chart and the King’s Health Questionnaire. Results 137 women with clinically proven OAB were recruited for the present study. 120 subjects were randomly allocated to the 3 different treatment groups after 17 women were excluded due to various reasons. Another 17 women dropped out during the treatment, thus leaving 34 women in the PFMT group, 34 in BAPFMT and 35 in ES to complete the present study. (Table1 to be presented) In comparing of the characteristics of the 3 groups, significant differences were noted both between the BAPFMT and ES groups as well as between the ES and PFMT groups in gravity (p=0.22, p=0.003, respectively), and number in menopause (p=0.025, p=0.001, respectively). A significant difference in parity (p=0.01) was also noted between the ES and PFMT groups. (Table2 to be presented) With regard to pelvic floor muscle strength, compared to the ES group, in both the BAPFMT and PFMT groups there were significant improvements in the differences between pre-and post-treatment scale of power (p�0.001, p�0.001, respectively), times of fast contraction (p=0.007, p=0.012, respectively), and degree of vaginal pressure (p�0.001, p�0.001, respectively). However, between the BAPFMT and PFMT groups there were no significant pre- and post-treatment differences of the 3 variables mentioned above. (Table3 to be presented). The changes in Domains 7(emotions), 9(severity measures) and 10(total score) of the King’s Health Questionnaire revealed significant differences between the BAPFMT and ES groups (p=0.003, p=0.029 and p=0.025, respectively). The changes in these domains when comparing the ES and PFMT groups revealed significant differences as well (p=0.007, p=0.001 and p=0.001, respectively). However, the changes in these same domains revealed no significant differences between the BAPFMT and PFMT groups. (Figure1 to be presented)

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Median (range) adherence, with treatment was 0.833 (0.25, 1.00) for the BAPFMT group, 0.791 (0.58, 1.00) for the ES group and 0.750 (0.54, 1.00) for the PFMT group (p=0.356, Kruskal-Wallis test). Conclusions Based on the comparison of the main outcome measures, either BAPFMT or PFMT resulted in significantly better pelvic floor muscle strength and better life quality than ES. Thus, either BAPFMT or PFMT is more effective than ES in the management of OAB in women. 112 Abramov Y1, Kwon C1, Gandhi S1, Goldberg R1, Sand P1 1. Evanston Continence Center, Evanston Northwestern Healthcare, Northwestern University LONG-TERM ANATOMIC OUTCOME OF DISCRETE SITE-SPECIFIC DEFECT REPAIR VERSUS STANDARD POSTERIOR COLPORRHAPHY FOR THE CORRECTION OF ADVANCED RECTOCELE: A 1 YEAR FOLLOW-UP ANALYSIS Aims of Study Repair of discrete site-specific defects in the Denonvillier’s “fascia” has been advocated as a surgical method for correction of advanced rectocele. Some investigators have reported a more favorable subjective outcome for this method with regards to bowel symptoms and sexual function, and similar anatomic outcome as compared to the standard posterior colporrhaphy (1, 2). All of these reports, however, have been descriptive and no comparative studies have been published. The current study compares anatomic outcomes of these two surgical techniques 1 year postoperatively. Methods Charts of all patients who underwent surgical repair for advanced rectocele by either standard posterior colporrhaphy or by the discrete site-specific defect repair techniques at a single institution between January 2000 and June 2001 were systematically reviewed. Primary outcome measures recorded were preoperative and 1-year postoperative pelvic exams by the Baden-Walker and POP-Q techniques. Concomitant procedures, estimated blood loss and complication rates were recorded. Statistical analysis was performed using the student t-test for continuous variables; and Chi-square and Fisher-exact tests for non-parametric variables. Logistic regression analysis, with rectocele recurrence as the dependent variable, was used to screen each risk factor separately for an association with this outcome. Results During this time period, 97 patients underwent standard posterior colporrhaphy and 116 patients underwent discrete site-specific defect repair for correction of advanced rectocele. Standard posterior colporrhaphy was performed by direct plication of the endopelvic connective tissues in the midline using a continuous imbricating 0-Vicryl suture or by several single horizontal mattress sutures. Site-specific defect repair was performed as previously described (1,2) including identification and closure of all discrete defects found in the Denonvillier’s “fascia” after its dissection away from the overlying vaginal epithelium. During this study period, all site-specific repairs consisted of reinforcement of the Denonvillier’s “fascia” layer to the perineal body and laterally to the endopelvic connective tissues and lavator masculature One year postoperative surveillance was available for 59 patients following discrete site-specific defect repair and 53 patients following posterior colporrhaphy. Age (72 vs. 70 yrs), parity (2.61 vs. 2.86) BMI (26.8 vs. 26.2) and preoperative degree of prolapse (2nd degree: 27% vs. 25%; 3rd degree: 22% vs. 17%; 4th degree: 51% vs. 58%) were not significantly different between the site-specific defect repair and the posterior colporrhaphy groups. Associated procedures were similar in both groups (hysterectomy: 35% vs. 29%; anterior colporrhaphy: 95% vs. 93%; incontinence procedure: 89% vs. 87% and vaginal vault suspension: 39% vs. 31%). Estimated blood loss (302cc vs. 281cc) and intraoperative complication rates (including hemorrhage: 2 vs. 3 patients; wound infection: 2 vs. 1 patient; and medical complications: 3 vs. 2

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patients) were not significantly different in the site-specific defect repair vs. the standard posterior colporrhaphy groups. At one year of follow-up, recurrence of rectocele beyond the midvaginal plane ( 2nd degree) was noted in 7 patients (13%) from the posterior colporrhaphy group and 19 patients (32%) from the site-specific defect repair group (p= 0.015) (Table 1). Postoperative Ap (-2.36 vs. -2.00 cm) and Bp (-2.43cm vs. -2.09 cm) indicated a trend towards less prolapse in the posterior colporrhaphy group, however, these differences were not statistically significant. Most recurrences in both the posterior colporrhaphy (78%) and the site specific defect repair (81%) groups were asymptomatic.

Table 1: One year postoperative anatomic outcome following posterior colporrhaphy versus site specific defect repair

Outcome measure Post. Colporrhaphy Site-Specific Repair P (N=53) (n=59) Preoperative Rectocele* 53 (100%) 59 (100%) 1.0 Ap point -0.86 ± 0.25 -0.79 ± 0.17 0.79 Bp point -0.47 ± 0.18 -0.61 ± 0.18 0.80 One year postoperative

Rectocele* 7 (13%) 19 (32%) 0.015♣ Ap point -2.36 ± 0.17 -2.00 ± 0.20 0.19 Bp point -2.43 ± 0.17 -2.08 ± 0.18 0.19 Blood loss (mL) 281 ± 20 302 ± 25 0.51 * 2nd degree and above ♣A statistically significant difference Conclusions These results suggest that site specific defect repair for advanced rectocele is associated with a significantly higher long term anatomic recurrence rate as compared to the standard posterior colporrhaphy. These findings should be weighed against the potential subjective benefits of the site specific defect repair technique. References 1. Porter W, Steele A, Walsh P, Kohli, N, Karram M. The anatomic and functional outcomes of defect-specific rectocele repairs. Am J Obstet Gynecol 1999; 181: 1353-8 2. Kenton K, Shott S, Brubaker L. Outcome after rectovaginal fascia reattachment for rectocele repair. Am J Obstet Gynecol 1999; 181: 1360-63.

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113 Karantanis E1, Stanton S1, Parsons M2, Robinson D2, Blackwell A L3, Cardozo L2, Moore K3 1. St George's Hospital, London, 2. King's College Hospital, London, 3. The St George Hospital, Sydney WOMEN’S PREFERENCES FOR TREATMENT FOR STRESS INCONTINENCE-PHYSIOTHERAPY OR SURGERY Aims of Study The conventional first line treatment for Urodynamic Stress Incontinence (USI) is conservative. However, in an era of informed choice, some women have shown a preference for surgery. We sought to determine the prevalence of treatment preferences and the reasons behind them, particularly the degree of influence of GP information, hearsay, and social factors.

Methods A package was developed for women with USI, consisting of three sequenced sections: 1) a questionnaire eliciting patients' current knowledge of available treatments including the origins of their knowledge; 2) three one-page information sheets describing Pelvic Floor Treatment (PFT) by women’s health physiotherapists, the TVT and Open Colposuspension as options for treatment, including success rates and complications; and 3) a questionnaire eliciting handwritten responses about patients’ preferred treatment, the reasons for their choice, and whether they wished to ask any questions. The package was developed by three urogynaecologists, two physiotherapists, and a professor of medical sociology. It was used in three Urogynaecology Units in two countries in a consecutive group of patients with a sole diagnosis of USI. Members in each unit adopted a policy of not discussing treatment options prior to completion of the questionnaire, which was offered either before or immediately following urodynamic diagnosis. The patients were informed that regardless of their preferences, the final decision about treatment modality would be made jointly between themselves and a doctor after the questionnaire was completed.

Exclusion criteria were: a) detrusor overactivity or dysfunctional voiding b) prior physiotherapy or continence surgery; c) concomitant prolapse deemed to require surgery; d) prior discussion of treatment options by a team member; or e) poor literacy in English.

Based on an estimation that 70% of women would choose pelvic floor treatment over surgery, and an estimated prevalence of 240 cases of USI per year between the three units, a sample size of 138 was determined.

Results Ninety-seven questionnaires were analysed but only 66, mean age 49 (SD+/-12) met all exclusion criteria. After reading the information sheets, 44 (66%) women chose PFT as their preferred management, followed by the TVT (24%) and Colposuspension (9%) with no significant differences between the three units (P=0.40; P=0.29 Fisher’s Exact Test). The basis for women’s choices were the information sheets (83%), the advice of another medical practitioner (3%) and the advice of a friend or relative (3%). Nine percent of women attempted to avoid making a preference, requiring encouragement and guidance by the doctor administering the questionnaire. Of the 44 women who chose PFT, 67% cited non-invasiveness and low risk as the main reason. Ten percent wanted to avoid a possible caesarean section in the event of a subsequent pregnancy. Of those who chose the TVT, the predominant reasons were failed home pelvic floor exercises (25%), the minimal invasiveness of the TVT (23%), and the early discharge and recovery associated with this procedure (29%) compared to colposuspension. Of those who chose colposuspension, the most common reason (50%) was that it sounded more permanent than the TVT. Forty-two percent of women said that their GP’s did not discuss treatment options. Patients who stated that their GP’s discussed only physiotherapy (N= 20) chose this treatment in 80% of cases. By contrast, those whose GP’s discussed only surgery (N=6), chose PFT in only 17% of cases. Similarly, of 7 patients who indicated they knew of friends who were happy with their surgical treatment, 6 chose a surgical option. In 19 women whose GP’s did not discuss treatment, and who did not hear of friends choices, 74% chose PFT, which was not significantly different to the overall PFT rate (Fishers exact P=0.55).

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There were 38 (58%) women who wanted to ask a question. The most common question was: "What does the doctor think is best for me” (23%). Conclusion Making a decision purely on factual information is difficult for many women. However, when given standardised unbiased information, 33% of women were prepared to bypass PFT and chose surgery, citing failed home pelvic floor training, minimal invasiveness, and fast recovery as the predominant reasons for TVT, and long-lasting effect for Colposuspension. Two-thirds of women chose Pelvic Floor Treatment, citing low risk as the main reason. These are informed choices based on standardised information sheets, and may suggest that women choosing surgical options have a speedier course to surgery. Whether in an era of informed choice, women choosing surgery should be permitted to bypass PFT is beyond the scope of this study, but is a matter for debate. The influences behind women’s preferences are unclear. However it may be that women whose GP’s or friends emphasise one treatment, are likely to come to urogynaecology units with predetermined preferences and are likely to choose them. 114 Drutz H1, Cardozo L2, Baygani S 3, Bump R3 1. Mt. Sinai Hospital, 2. Kings College Hospital, 3. Lilly Research Laboratories DULOXETINE TREATMENT OF WOMEN WITH ONLY URODYNAMIC STRESS INCONTINENCE AWAITING CONTINENCE SURGERY Aims of Study Duloxetine hydrochloride, a potent and selective inhibitor of serotonin (5-HT) and norepinephrine (NE) reuptake, is believed to increase efferent output from Onuf’s nucleus via stimulation of pudendal motor neuron alpha-1 adrenergic and 5 HT-2 receptors, resulting in enhanced contractility of the rhabdosphincter [1]. One phase 2 and three phase 3 randomised placebo-controlled clinical trials have demonstrated significant efficacy for duloxetine for women with mild, moderate, and severe stress urinary incontinence (SUI) [2]. The primary aim of this randomised clinical trial was to assess the efficacy of duloxetine in the treatment of women with severe SUI symptoms due to urodynamic stress incontinence only and who were awaiting surgery for SUI. Methods 109 women aged 33-75 years at 14 clinical centres in Canada (7 centres), the UK (4 centres), the Netherlands (2 centres), and Australia (1 centre), were enrolled into this double-blind, placebo-controlled study. The case definition was a predominant symptom of SUI with a weekly stress incontinence episode frequency (IEF) ≥14, the confirmation of urodynamic stress incontinence only within the 6 months preceding enrolment, the woman’s decision to proceed with continence surgery, and the woman’s having been scheduled for such surgery. After a 2-week placebo lead-in period, women were randomly assigned to receive placebo (N = 54) or duloxetine 80 mg/day (N = 55; 40 mg bid) for 4 weeks followed by a forced dose escalation to 120 mg/day (60 mg bid) for another 4 weeks. Assessment variables included IEF and continence pad use, both recorded real-time on paper diaries prior to each visit, the Incontinence Quality of Life (I-QOL) questionnaire total and subscale scores, the Patient Global Impression of Improvement (PGI-I) and Severity (PGI-S) ratings, and the Willingness to Consider Surgery (WCS) rating. Van Elteren’s test was used to analyze the percent changes in IEF and pad use. Analysis of covariance was used to analyze mean changes in I-QOL scores. The PGI-I and WCS were analysed using the Cochran-Mantel-Haenszel test. All analysis was based on Intent-to-Treat principles. Results The mean baseline IEF was 22.3/wk; 89% of women rated their incontinence as moderate or severe. The table lists the changes in IEF, I-QOL total and subscale scores, and pad use by treatment. All variables showed significant improvements with duloxetine compared with placebo. 33.3% of these

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severely incontinent women taking duloxetine rated themselves as much better or very much better compared with 7.7% of those taking placebo (p = .006). There were some additional improvements in both IEF and I-QOL total score with duloxetine dose escalation (Figure), but the differences between the 40 mg bid and 60 mg bid responses were not statistically significant. Before enrolling in the trial, 39% of women were scheduled for retropubic urethropexies, 13% for slings, 46% for TVTs, and 2% for other procedures. After treatment, 10 of 49 (20%) women who considered surgery before starting duloxetine said they were somewhat or very much not interested in surgery after taking duloxetine, compared with none of 45 after taking placebo (p =.001). Side effects were more common with duloxetine and the profile

was compatible with that described in previous larger studies. Most side effects had their onset prior to the duloxetine dose escalation.

I-QOL Score Improvements Median Weekly IEF Decrease

Total

Social Embarrassment Subscale

Avoidance & Limiting Behavior Subscale

Psychosocial Impact Subscale

Median Weekly Pad Decrease

Placebo 27% 2.4 3.6 2.0 2.1 4.8% Duloxetine 60% 10.6 11.5 10.1 10.6 34.5% p-value <.001 .003 .008 .01 .002 .008 Conclusions This study provides evidence for the efficacy of duloxetine in women with severe SUI due to urodynamic stress incontinence who have decided to proceed with continence surgery. The data suggest that some women may reconsider proceeding with their scheduled surgery after treatment with duloxetine. Increasing the duloxetine dose from 80- to 120-mg per day did not have a significant impact on either the efficacy or side effect profile of duloxetine, although some additional efficacy was observed. References 1. Effects of duloxetine, a combined serotonin and norepinephrine reuptake inhibitor, on central neural

control of lower urinary tract function in the chloralose-anesthetized female cat. J Pharmacol Exp Ther 1995;274:1014-24

2. Duloxetine for stress urinary incontinence: meta-analysis of worldwide efficacy. Presented at the Society for Urodynamics and Female Urology meeting, Chicago, April 2003

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Changes in IEF and I-QOL by visit, duloxetine versus placebo; duloxetine dose was 40 mg twice daily at 4 weeks and 60 mg twice daily at 8 weeks.

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115 Tamussino K1, Hanzal E2, Kölle D3, Ralph G4, Riss P5 1. Department of OB/GYN, University of Graz, 2. Dept. OB/GYN, University of Vienna, 3. Dept. OB/GYN, University of Innsbruck, 4. Dept. OB/GYN, KH Bruck a.d. Mur, 5. Dept. OB/GYN, KH Mödling THE TENSION-FREE VAGINAL TAPE OPERATION: RESULTS OF A REGISTRY Aims of Study The tension-free vaginal tape (TVT, Ethicon) operation was introduced in our area in 1998 and quickly became popular. In 1999, in the absence of completed randomized trials, we initiated a central registry to assess the use of and perioperative complications with the new operation. The registry was later expanded to include other vaginal tape systems. Methods 65 gynecology units agreed to participate and entered patients. Per operation a single-page questionnaire was completed containing items on the patient (age, parity, previous gynecologic surgery), the operation (operating time, concomitant procedures, anesthesia, intraoperative problems, bladder drainage), and the postoperative period (days until residual urine <100 mL, postoperative stay, reoperation). Results As of 1 March 2003 a total of 5157 patients undergoing the TVT operation were entered. The number of reports of other vaginal tape systems than the TVT was too small for meaningful analysis. 1453 women (28%) had undergone previous surgery for prolapse or incontinence, including 206 Burch colposuspensions. 59% of TVTs were performed in isolation, 41% with other procedures. Most concomitant operations were for pelvic organ prolapse. The results in patients undergoing a TVT procedure with or without a concomitant operation are shown in Table 1. The bladder perforation rate was 2.9% overall and higher in women with than in those without previous surgery (4.7% vs. 2.2%, P<.05). The bladder perforation rate among 206 women after colposusension was 5.3%. There appeared to be no lasting sequelae of bladder perforation.

Table 1. Perioperative Data TVT in combination (N = 2128)

TVT only (N = 3029)

Operating time (min., median, range) 81 (15-390) 30 (9 -172)

Anesthesia

Local 5% 45%

Regional 48% 42%

General 47% 13%

Bladder drainage

Intermittent catheterization 6% 26%

Urethral Foley 65% 61%

Suprapubic 27% 6%

Intraoperative complications

Bleeding 2.0% 1.9%

Bladder perforation 53 (2.5%) 95 (3.1%)

Postoperative stay (days) 7 (0-65) 3 (0-37)

Days until residual urine <100 mL 3 (0-95) 1 (0-64)

There were 138 reoperations (2.7%) for reasons related to the TVT. The most common cause of reoperation was urinary retention: 88 patients (1.7%) underwent division, loosening or removal of the TVT

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or secondary placement of a suprapubic catheter. 38 patients (0.7%) underwent reoperation for hematoma or bleeding. There was one small bowel injury treated successfully with bowel resection 2 days after TVT. One patient undergoing radical resection of recurrent vulvar cancer and TVT placement died of multiorgan failure due to sepsis 46 days after surgery. One patient developed necrotizing fasciitis of the lower abdominal wall. Conclusions The TVT quickly became a frequently perfomed operation in our area for patients with primary or recurrent stress incontinence. The bladder perforation rate is increased in women with previous urogynecologic surgery, particularly colposuspension, but there were no sequelae of perforation. The TVT operation is frequently performed with other surgery, most commonly for pelvic organ prolapse. There are considerable variations in clinical practice. For example, only 45% of isolated TVTs were performed with local anesthesia and 61% of patients undergoing a TVT only had an indwelling urethral catheter. The high rate of indwelling bladder drainage probably reflects the frequent use of regional anesthesia. Major complications were rare. Urinary retention [1] and hematomas account for the large majority of reoperations after TVT. References

1. Rardin CR, Rosenblatt PL, Kohli N, Miklos JR, Heit M, Lucente VR. Relaease of tension-free vaginal tape for the treatment of refractory postoperative voiding dysfunction. Obstet Gynecol 2002;100:898-902.

116 Kocjancic E1, Costa P 2, Wagner L2, Crivellaro S1, Gherzi R3, Gontero P1, Favro M1, Ceratti G1, Tarrano E1, Sala M1, Frea B1 1. Clinica Urologica, Ospedale Maggiore della Carità, Novara, 2. Hopital Gaston Doumerque, Nimes, France, 3. II Divisione Ostetricia e Ginecologia, Ospedale Maggiore della Carità, Novara SAFETY AND EFFICACY OF THE TRANS OBTURATOR TAPE IN THE TREATMENT OF STRESS URINARY INCONTINENCE Aims of Study In the past years many new surgical techniques have been presented for the treatment of urinary stress incontinence. The principal target of these therapies is achieving continence, reducing surgical invasiveness, and improving the safety and practicability of the procedure. The Trans Obturator Tape (TOT), is a new technique, based on an entirely new concept of positioning of a tape under the middle urethra horizontally through the obturator foramina. The safety, feasibility and efficacy of the TOT was evaluated. Methods The study was done using a tape named Obtape, produced by Porges Mentor. The tape is made of polypropylene, with a particular design which allows the in growth of the tissue and with interesting characteristics of elasticity (only 5%). This low elasticity permits an easier placement and accurate tension adjustment reducing the risk of an excessive tensing of the tape. Cadaveric dissection was performed to evaluate the anatomy of the obturator foramina. The female frozen cadaver was positioned in standard lithotomy position. A Foley catheter was inserted into the urethra and a small (2cm) incision was performed 1 cm below the external meatus in order to allow the digital dissection of the paraurethral space toward the internal surface of the pubic bone. Through the skin the obturator foramen was identified and another small incision was done in the medial part just above the level of the urethral meatus bilaterally .After that a hooked tunneler was inserted through the incision at the level of the obturator foramen. The tunneler is directed antero-posteriorly until the obturator fascia, which covers completely the obturator foramen, is perforated. After that the tunneler is turned and directed medially in the para urethral space previously prepared. The tunneler is inserted through the vaginal incision under direct digital control. The tiny extremity of the tape is inserted into the eye of the tunneler. Retracting the tunneler

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the tape enters the obturator foramina. The procedure is repeated on the other side. Particular care must be given to avoid extra tension under the urethra.

Subsequently the endopelvic space was opened and the endopelvic fascia prepared. Further more incising the pelvic fascia the urethra and the bladder neck was exposed and the obturator fossa was opened to isolate the tape. In the obturator fossa particular attention was paid to the relation between the tape and the obturator nerve and vessels. All the distances between the tape and the neighbouring anatomical structures were obtained. Furthermore 50 patients with urinary stress incontinence where treated with TOT. The mean age was 57 (range 36 – 76). 70% of the patients (35/70) had genuine stress incontinence (GSI), 30% (15/50) had stress incontinence associated with urgency. Patients where evaluated preoperatively and at one year follow up with a physical examination, Boney test, uroflowmetry and voiding diary. Results Cadaveric measurements :

( Average) Endopelvic space Obturator foramen Distance between lateral wall of urethra and tape

2 cm +/- 0,5 2 cm +/- 0,5

Distance between obturator nerve / vessels and tape

5 cm +/- 0,3 4 cm +/- 0,3

Angle urethra – tape 15 ° +/- 0,5 15 ° +/- 0,5 88% (44/50) patients where dry one year after the surgery and 12% (6/50) where improved. No perioperative complications where observed. In one case, complicated with extrusion of the tape and secondary infection the tape had been removed. One other patient had developed de novo instability, correlated with recurrent urinary tract infections). No statistically significantly changes in uroflowmetry parameters was observed after the surgery. Conclusions The trans obturator tape is a simple, direct and quick procedure with a very low risk of obturator nerve and vessel perforation due to the distance between these structures and the tape. The indications are represented by genuine stress incontinence as a primary surgical option or as a combined procedure during an anterior prolapse repair. The anatomical study shows that the TOT is a minimally invasive procedure with a very low risk of obturator nerve and vessel perforation due to the distance between these structures and the tape. This distance represents a considerable guarantee of safety of these structures at risk during this procedure. The tape is positioned below the endopelvic fascia which avoids bowel injury or risk of perforation of the iliac vessels, described for instance with TVT or similar procedures. The direction of the tape is a guarantee of avoiding hyper correction. The angle between the urethra and the tape is on average 15 degrees and no anti anatomical tensions which pushes the urethra toward the pubic bone are applied. The tape lies under the urethra re-establishing the anatomical support that restrains hypermobility. 117 Mansfield K1, Mitchelson F2, Moore K3, Burcher E 1 1. University of New South Wales, 2. Melbourne University, 3. Pelvic Floor Unit, St George Hospital MUSCARINIC RECEPTOR BINDING IN HUMAN DETRUSOR- AGE RELATED CHANGES. Aims of Study A costly consequence of old age is bladder dysfunction and incontinence. Ageing can bring disturbances in both the storage and voiding phases of bladder micturition. Urodynamic tests have demonstrated an age related reduction in bladder capacity, increased incidence of uninhibited contractions, decreased urinary flow rate, reduced voiding volume and incomplete bladder emptying (1, 2). Muscarinic receptor antagonists

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are the mainstay of therapy for patients with urinary incontinence disorders such as detrusor overactivity. However, such treatments are problematic due to side effects and a relative lack of antagonist subtype selectivity. The aim of this study was to use new subtype-selective muscarinic receptor antagonists and radioligand binding to investigate the affinity and receptor number of muscarinic receptors in detrusor, and to determine any age-related changes. Methods Specimens of normal human detrusor were collected from 21 control patients (median age 67, range 36–77 years; 15 males and 6 females) undergoing open bladder surgery (9 cystectomy, 9 radical prostatectomy, 3 colposuspension). Specimens were taken from macroscopically normal areas of the bladder and stored at –70oC until use. All patients displayed normal micturition frequency, with no urge incontinence. Radioligand binding with the muscarinic receptor ligand [3H]quinuclidinyl benzylate (QNB) was performed on membranes from the detrusor muscle. After removal of the mucosa, membranes were prepared by homogenising the muscle in 50 mM sodium phosphate buffer (3). Incubations were carried out for 2 h at 37oC. Nonspecific binding was defined using 10µM atropine. In saturation experiments, 8 concentrations of [3H]QNB (15 pM to 2 nM) were incubated with membranes in 50 mM sodium phosphate buffer (pH 7.4). In competition experiments, 200 pM [3H]QNB was incubated with increasing concentrations of a number of muscarinic receptor antagonists, whose subtype specificity is shown in Table 1. Incubations were terminated by filtration and washing with ice-cold buffer, through GF/B filters. Filter-bound radioactivity was quantified in a liquid scintillation counter. Protein content was determined by the Lowry method. Data were fitted to a one or two site model using the non-linear regression analysis program of GraphPad Prism (version 3) and are shown as mean pKi ± S.E.M. pKi is the negative log of the Ki. Results In saturation studies (n=12), [3H]QNB bound to a single high affinity site, of dissociation constant (Kd) 55.7 ± 11.9 pM and maximum receptor number (Bmax) 152 ± 7.5 fmol/mg protein. Regression analysis demonstrated an inverse correlation of receptor number (Fig. 1A) and receptor affinity (Fig. 1B) with age (note that receptor affinity is inversely proportional to Kd). Further analysis revealed that the decrease in Bmax with age was due to a decline in M2 receptor numbers, but no change in M3 receptor numbers, with increasing age (Fig. 1C).

50 55 60 65 70 750

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Figure 1. Regression analysis of [3H]QNB saturation binding data for human detrusor muscle membranes. Panel A shows a decrease in receptor number (Bmax) with age (r2 = 0.44, P = 0.019). In panel B the increasing Kd with age indicates a decrease in receptor affinity with age (r2 = 0.39, P = 0.03). Panel C demonstrates that the numbers of M2 ( ) receptors (r2 = 0.55, P = 0.02) but not M3 ( ) receptors (r2 = 0.07, P = 0.48) decline with increasing age. In competition experiments, several new subtype selective muscarinic antagonists were investigated. Some competitors, 4-DAMP, darifenacin (M3 receptor preferring) and methoctramine (M2 receptor preferring), displayed biphasic binding profiles, with high and low affinity Ki values compatible with a population of approximately 75% M2 receptors and 25% M3 receptors (see Table 1). The mamba toxins MT1 (M1 and M4 receptor preferring) and MT3 (M4 receptor preferring) showed poor affinity, consistent with negligible expression of these subtypes in detrusor muscle. However, pirenzepine (M1 receptor preferring) showed some high affinity binding, possibly due to its affinity for M3 receptors. There was no evidence for the presence of M5 receptors.

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Table 1. Radioligand binding data (mean ± S.E.M.) with [3H]QNB in detrusor muscle membranes

Drug Selectivity pKi ± S.E.M.

pKi ± S.E.M. Site H*

pKi ± S.E.M. Site L* % H

Atropine nonselective 8.7 ± 0.6 N/A AQ-RA 741 M2=M3>M5 8.1 ± 0.6 N/A 4-DAMP M3>M2 8.0 ± 0.6 9.7 ± 0.3 7.6 ± 0.5 22 ± 6 Methoctramine M2>M3 7.5 ± 0.6 7.9 ± 0.6 6.2 ± 0.4 74 ± 5 Darifenacin M3>M2 7.5 ± 0.6 9.7 ± 0.4 6.9 ± 0.6 23 ± 3 AF-DX 116 M2>M3 6.9 ± 0.5 N/A Pirenzepine M1>M3>M2 6.3 ± 0.6 8.9 ± 0.2 6.1 ± 0.6 15 ± 4 Mamba toxin 1 M1=M4 <<7.0 N/A Mamba toxin 3 M4 <<7.0 N/A * data best fitted (P<0.05) to 2 site binding with high (H) and low (L) affinity components. N/A: two site binding was not preferred, therefore only the one site binding results are shown Conclusions New subtype-selective muscarinic receptor antagonists have become available during the past decade. Previous studies examining muscarinic receptor binding in human detrusor were performed before these subtype-selective antagonists were available. This study concurs with previous findings that the M2 subtype is the predominant muscarinic receptor in human detrusor. There is little evidence from our radioligand binding for the presence of M1, M4 or M5 receptors in human detrusor. The novel finding from this work was the decrease in muscarinic receptor population with increasing age. This has not previously been reported, although functional detrusor muscle experiments have shown decreased contractile responses to acetylcholine with advancing age (4). The present study reveals that the age-related decline was specific for M2 receptors, but not for M3 receptors. These results raise the possibility of a role for M2 receptors in the development of bladder contractility disorders, which are known to be more common in the elderly. References 1. J Urology (2001) 166: 721-727 2. Urology (1998) 51: 206-212 3. Eur J Pharmacol (1993) 246: 1-8. 4. Exp Geront (2001) 36: 99-109 118 Landis J R1, Kaplan S2, Swift S3, Versi E4 1. Center for Clinical Epidemiology and Biostats, University of Pennsylvania School of Medicine, PA, 2. College of Physicians and Surgeons and Physicians, Columbia University, USA, 3. Department of Obstetrics and Gynecology, Medical University of South Carolina, SC, USA, 4. Pharmacia Corporation, Peapack, NJ IMPACT OF URGE INCONTINENCE SEVERITY ON DRUG TREATMENT EFFICACY Aims of Study Urinary incontinence is often the key symptom associated with assessment of OAB symptom severity and the decision to use drug therapy. Furthermore, patients with more severe symptoms are typically those most likely to seek treatment and it is commonly perceived that such patients are more difficult to treat. However, data on the impact of incontinence severity on antimuscarinic treatment efficacy in patients with OAB are very limited. We therefore evaluated the efficacy of tolterodine extended-release (TER) in OAB patients with severe incontinence.

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Methods Patients aged ≥18 years old with urge incontinence (≥5 episodes/week), urinary frequency (≥8 micturitions/24 hours) and symptoms of OAB for ≥ 6 months were enrolled into a multinational, randomized, double-blind, placebo-controlled trial conducted at 159 centers in North America, Europe and Australia/New Zealand. Patients were randomized to receive TER 4 mg once daily or placebo for 12 weeks. Severe incontinence was defined as ≥21 episodes/week. Changes in the number of incontinence episodes/week and micturition frequency after 12 weeks were compared between treatments with SAS PROC FREQ and StatXact, using generalized Mantel-Haenszel procedures (based on rank scores) to adjust for the variation among baseline severity strata and clinical centers. Results A total of 986 patients were eligible for this post-hoc analysis (TER, n=492; placebo, n=494). After 12 weeks, overall absolute median reductions in weekly incontinence episodes were significantly greater with TER (9.0 episodes/week; 70.8% reduction) than with placebo (5.0 episodes/week; 34.1% reduction; p<0.02). In the subgroup of patients with severe incontinence, the median number of incontinence episodes/week at baseline was similar in both placebo (31.5; n = 210) and TER (34; n = 171) groups. For patients with severe incontinence at baseline, the median reduction in incontinence episodes was significantly (p<0.001) greater with TER (21.0 episodes/week; 68% reduction) than with placebo (9.5 episodes/week; 30% reduction) after 12 weeks (p=0.022, adjusted for baseline incontinence severity strata and clinical center). There was also a significantly (p<0.02) greater reduction in micturition frequency with TER (median decrease of 1.9 episodes/24 h; 17.4% reduction) than with placebo (median decreases of 0.4 episodes/24 h; 4.5% reduction) in this severe incontinence patient-subgroup, adjusted for baseline incontinence severity and clinical center. In patients with non-severe incontinence at baseline (5 – 20 incontinence episodes/week), the median reduction in incontinence episodes was also significantly (p<0.03) greater with TER (6 episodes/week; 71% reduction) than with placebo (4 episodes/week; 39% reduction) after 12 weeks of treatment, when adjusted for baseline incontinence severity strata and clinical center. The median reduction in number of incontinence episodes/week increased with baseline severity in both treatment groups, with tolterodine ER more effective than placebo irrespective of symptom severity (Figure 1). Moreover, the median percentage reduction in the number of incontinence episodes/week was comparable across the whole range of baseline severity strata (Figure 2). Conclusions During treatment with TER, patients with severe incontinence at baseline experienced a significant percentage reduction in incontinence episodes similar to that achieved in patients with less severe incontinence. This corresponded to a greater absolute reduction in incontinence episodes in the severe incontinence subgroup. Therefore, the benefits of antimuscarinic treatment may be greater in these severely incontinent patients than has previously been reported in clinical studies in OAB. Figure 1. Median absolute change in urge incontinence per week stratified by baseline incontinence severity in patients receiving tolterodine ER or placebo for 12 weeks.

- 4 0

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5 - 1 0 1 1 - 1 5 1 6 - 2 0 2 1 - 2 5 2 6 - 3 5 3 6 - 4 5 ≥ 4 6

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Figure 2. Median percentage change in urge incontinence per week stratified by baseline incontinence severity in patients receiving tolterodine ER or placebo for 12 weeks.

119 Bowden A1, Colman S2, Sabounjian L 3, Sandage B 3, Schwiderski U 3, Zayed H2 1. The Lewin Group, Quintiles UK, 2. Quintiles Late Phase, 3. Indevus Pharmaceuticals PSYCHOMETRIC VALIDATION OF AN URGENCY SEVERITY SCALE (IUSS) FOR PATIENTS WITH OVERACTIVE BLADDER. Aims of Study This U.S. study sought to validate the psychometric properties of an Urgency Severity Scale (IUSS), a new patient-reported outcome assessment instrument for patients with overactive bladder (OAB). The IUSS required a ‘quality assessment’ to ensure it is a valid, reliable and responsive patient-reported outcome assessment tool. Methods This study was based on data collected as a result of administering the IUSS during a 12-week multi-center, parallel, randomized, double-blind, placebo-controlled clinical trial of trospium chloride in patients with OAB associated with predominant urge incontinence. The IUSS was contained within a ‘patient urinary diary’ that was completed by patients during four 1-week periods in the course of the trial. The IUSS asks patients about their ‘degree of urgency’ of their toilet voids, and requires that they rate the degree of urgency on a scale as follows: 0: NONE - no urgency 1: MILD - awareness of urgency, but easily tolerated 2: MODERATE - enough urgency discomfort that it interferes with usual activity/ tasks 3: SEVERE - extreme urgency discomfort that abruptly stops all activity/tasks

- 1 0 0

- 7 5

- 5 0

- 2 5

0

P la c e b o T o lte r o d in e E R

B a s e l in e in c o n t in e n c e s e v e r i t y ( e p is o d e s /w e e k )

5 - 1 0 1 1 - 1 5 1 6 - 2 0 2 1 - 2 5 2 6 - 3 5 3 6 - 4 5 ≥ 4 6

S e v e r e in c o n t in e n c e s u b g r o u p

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The patient urinary diary also collected information on the number of toilet voids, urge incontinence (UI), and stress incontinence episodes; and the volume voided (mL). In addition, patients completed the Incontinence Impact Questionnaire (IIQ). Patients were randomized to receive either trospium chloride or placebo, however for the psychometric assessment all patients were pooled into one cohort (n=523). Sensitivity analysis was conducted to ensure that the inclusion of the trospium group into the patient cohort at week 12 was a valid approach. There were two distinct study periods for the psychometric assessment referred to as the baseline and week 12 data collection periods. Psychometric methods used to evaluate new and adapted patient-reported outcome instruments include standard procedures for the assessment of reliability, validity and responsiveness. Construct validity of the IUSS was assessed by correlating IUSS scores with urinary frequency, frequency of UI episodes, average volume voided per toilet void, and scores on the IIQ. The Mann-Whitney U and CMH tests were used to determine if the IUSS could distinguish between patient’s frequency of toilet voids and UI episodes. The effect size statistic was used to assess the responsiveness of the IUSS using toiled void and UI frequency as external criteria to categorize the patients as responders or not. Correlating IUSS scores between day 1 and day 7 at baseline, and day 2 and day 5 at baseline assessed the test-retest reliability of the IUSS. Content validity and respondent burden were examined through a literature review. P-values ≤0.05 were considered significant; p-values >0.05 and ≤0.10 were thought to represent a trend towards significance. Results This study demonstrated the IUSS to be psychometrically sound in terms of construct, content and known groups validity, test-retest reliability and to be responsive to change. The IUSS distinguished between those who scored above and below the median number of toilet voids per 24 hours as well as the median number of UI episodes per 24 hours at baseline and week 12 periods (p<0.01). The IUSS was highly responsive to change in the average number of toilet voids per 24 hours (effect size 1.17) and the average number of toilet voids and UI episodes per 24 hours combined (effect size 1.39). It was moderately responsive to change in the average number of UI episodes per 24 hours (effect size 0.49). The IUSS has low-to-moderate correlation with frequency of toilet voids, frequency of UI episodes and scores on the IIQ. IUSS scores did not correlate with the average volume voided (mL) per toilet void. The test-retest reliability of the IUSS for day 1 vs. day 7 during the baseline period was moderate (0.66) and high (0.80) for day 2 vs. day 5 during the baseline period. The content validity of the IUSS determined that it is a measure of the magnitude (or severity) of urgency associated with OAB and can also be used to determine the frequency of urgency associated with toilet voids. The IUSS is a single-item scale with four possible responses and therefore the respondent burden is minimal. Conclusions The IUSS is a single-item scale that has been developed as a self-report instrument for use in clinical trials. It is a measure of the magnitude (severity) of urgency associated with OAB and can also be used to determine the frequency of urgency associated with toilet voids. The psychometric assessment of the IUSS performed retrospectively on data collected during a 12-week clinical trial for trospium chloride demonstrated the IUSS to be a psychometrically valid scale in terms of construct, content and known groups validity, test-retest reliability, and to be responsive to change.

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120 Dmochowski R1, Staskin D2, Appell R3, Zinner N4, Gittelman M5, Davila G6, Sand P7 1. Vanderbilt University, Nashville, 2. New York Weill Cornell Medical Center, New York, 3. Baylor College of Medicine, Texas Medicine Center, Houston, 4. UCLA, Western Clinical Research, Doctors Urology Group, Torrance, 5. Uromedix, Aventura, 6. Cleveland Clinic Florida, Weston, 7. Northwestern University, Chicago THE EFFICACY, EFFECTIVENESS, AND SAFETY OF TRANSDERMAL OXYBUTYNIN IN PATIENTS WITH OVERACTIVE BLADDER Aims of Study Oxybutynin (OXY) is a mainstay in the treatment of overactive bladder (OAB). In its oral form, the drug undergoes extensive hepatic and gastrointestinal presystemic metabolism to form a primary active metabolite, N-desethyloxybutynin (DEO). This metabolite is present in the circulation at levels 4 to 10 times higher than that of the parent compound and appears to be responsible for many of the drug’s anticholinergic adverse events (AEs). Transdermal delivery of OXY, which avoids presystemic metabolism, produces a DEO concentration that is only 1.5 times greater than parent, and subsequently generates fewer anticholinergic AEs comparable to placebo while providing efficacy that is comparable to that of oral formulations. The aim of this investigation is to compare the safety and efficacy of OXY transdermal delivery system (OXY-TDS) versus placebo during 12 weeks of treatment. Methods Pooled data from 2 placebo-controlled studies: Study 1 is a double-blind, placebo-controlled study of 249 urge urinary incontinence (UI) patients. Study 2 is a double-blind, active- and placebo-controlled study of 238 urge and mixed UI patients. Symptom requirements recorded in 3-day and 7-day urinary diaries for Studies 1 and 2, respectively, after prestudy treatment washout, included 10 or more urge UI episodes in study 1 and 4 or more episodes in study 2; 56 or more voids in study 1 and 24 or more voids in study 2; and 350 mL or less urinary void volume in both studies. The efficacy end points of this study were the change from baseline to end point in the number of incontinence episodes, comparisons of daily urinary frequency, and urinary void volume. The safety end points were the confirmation of continued efficacy and continued adherence to therapy. As OXY-TDS continuously releases OXY over a 3.5 to 4 day period, OXY-TDS 3.9 mg/day or matching placebo system was applied to the abdomen twice weekly. Patients were 91.9% female, 92.4% Caucasian, and had a mean age of 62.4 years, with 49.8% of patients 65 years and older; 40.6% had no previous anticholinergic experience. Results Urinary incontinence episodes, frequency, and void volume improved significantly for active treatment versus placebo (Table 1). The most common AE for OXY-TDS was localized application site pruritus and erythema accompanied by a low incidence of systemic anticholinergic side effects comparable to that of placebo (Table 2). Most patients presented AEs that were mild to moderate in severity. Of the 487 patients, 30 (6.2%) withdrew – OXY, 27 (11.2%); placebo, 3 (1.2%) – due to drug-related AEs. Combining both the active treatment and placebo arms of the study, most patients (83.9%) experienced no application site reactions during the study. Similarly, most patients in the OXY-TDS arm (93% vs. 94.7% for placebo) experienced no dry mouth. Table 1: Changes From Baseline in Adult Patients With Overactive Bladder Who Received OXY-TDS or

Placebo for up to 12 Weeks End Points – Change From Baseline*

OXY-TDS 3.9 mg/d 2x/wk* Placebo* P value

(vs Placebo) Daily UI episodes -2.9 ± 2.77 -2.4 ± 3.05 .0004 Average daily urinary frequency

-2.1 ± 2.59 -1.56 ± 2.83 .0023

Average urinary void volume

31.8 mL ± 60.34 mL 9.9 mL± 59.87 mL <.0001

* Mean ± SD

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Table 2: Treatment-Emergent Adverse Events

Adverse Event OXY-TDS 3.9 mg/d (N=242)

Placebo (N=245)

Dry mouth 17 (7.0%) 13 (5.3%) Constipation 5 (2.1%) 5 (2.0%) Diarrhea 6 (2.5%) 5 (2.0%) Application site pruritus 39 (16.1%) 13 (5.3%) Application site erythema 17 (7.0%) 6 (2.4%) Conclusions OXY-TDS 3.9 mg/day administered in a twice-weekly regimen is an effective, safe, and well-tolerated treatment for patients with symptoms of OAB. The significant mean reductions in the number of incontinence episodes and urinary frequency, along with the increase in void volume, support the efficacy of the transdermal system. OXY-TDS was associated with a low incidence of anticholinergic AEs, comparable to placebo. Local application site reactions were consistent with those observed in the safety profile of other matrix transdermal systems and are generally mild to moderate (pruritus and erythema). These combined efficacy and tolerability data suggest that OXY-TDS confers unique clinical effectiveness in the management of patients with OAB. 121 Chapple C1, Rechberger T2, Al-Shukri S3, Meffan P 4, Everaert K5, Ridder A6 1. Royal Hallamshire Hospital, 2. Akademia Medcyzna Lublinie, Poland, 3. St Petersburg Pavlov Medical University, 4. Roundhay Med Centre, New Zealand, 5. University of Gent, Belgium, 6. Yamanouchi Europe BV, The Netherlands RESULTS OF A RANDOMIZED PHASE 3 STUDY COMPARING SOLIFENACIN SUCCINATE WITH TOLTERODINE AND PLACEBO IN PATIENTS WITH SYMPTOMATIC OVERACTIVE BLADDER Aims of Study The full therapeutic potential of antimuscarinic agents, the mainstay treatment for overactive bladder (OAB), is limited by side effects such as dry mouth. Solifenacin succinate (Vesicare®; YM905) is a new, bladder-selective antimuscarinic agent suitable for once-daily administration. In this phase 3 study, the primary objective was to assess the efficacy of solifenacin 5 mg and 10 mg once daily in patients with OAB. Secondary objectives were to evaluate the safety and tolerability of solifenacin and to compare the efficacy and safety of solifenacin with tolterodine 2 mg twice daily. Methods Male and female patients aged ≥18 years with symptoms of OAB for 3 months or more first entered a 2-week, single-blind placebo run-in period. Patients were subsequently randomized to 12-week double-blind treatment with solifenacin 5 mg (n = 279) or 10 mg (n = 268), tolterodine (n = 263), or placebo (n = 267). The primary efficacy variable was mean change in mean number of micturitions/24 h from baseline to endpoint. Secondary efficacy variables included mean change in number of episodes of urgency and incontinence and mean change from baseline in volume voided per micturition. Results The efficacy evaluation included 1033 patients (253 placebo, 266 and 264, solifenacin 5 mg and 10 mg, respectively, and 250 tolterodine). Solifenacin, at both 5-mg and 10-mg doses, was significantly more effective than placebo in improving all OAB symptoms (Table). Compared with placebo, tolterodine produced lesser, nonsignificant reductions in episodes of urgency and incontinence than did solifenacin.

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Over 50% of solifenacin-treated patients incontinent at baseline became continent by study end. Incidences of dry mouth, the most bothersome side effect, were 4.9% (placebo), 14.0% (solifenacin 5 mg), 21.3% (solifenacin 10 mg), and 18.6% (tolterodine). Treatment with solifenacin was well tolerated, with a low discontinuation rate.

Solifenacin Variable

Placebo 5 mg 10 mg

Tolterodine

Mean change from baseline to endpoint: episodes/24 h* Micturitions −1.20 −2.19a −2.61b −1.88c Urgency −1.41 −2.85b −3.07b −2.05 Urge incontinence −0.62 −1.41d −1.36e −0.91 Volume voided/micturition 7.4 32.9b 39.2b 24.4b *Full analysis set. Difference vs placebo: aP = 0.0003; bP = 0.0001; cP = 0.0145; dP = 0.0020; eP = 0.0028. Conclusions Solifenacin succinate 5 mg or 10 mg once daily produces a significant improvement in the symptoms of OAB. Solifenacin is a highly active new agent with a favorable therapeutic index for treatment of OAB. 122 Robinson D1, Dixon A 1, Cardozo L1, Anders K 1, Balmforth J1, Parsons M1 1. Kings College Hospital DOES ANTIMUSCARINIC THERAPY EXACERBATE VOIDING DIFFICULTIES? Aims of Study Antimuscarinic therapy, in conjunction with bladder retraining, remains the management of choice for women complaining of symptoms suggestive of an overactive bladder and a urodynamic diagnosis of detrusor overactivity (1). The development of newer long acting, and highly specific, antimuscrinics has reduced adverse effects such as dry mouth, constipation and somulence although there is a lack of documented evidence regarding their effect in women with concomitant voiding difficulties. The purpose of this study was to investigate the hypothesis that by suppressing spontaneous detrusor contractions antimuscarinic therapy may worsen symptoms of voiding difficulty and lead to a reduction in flow rates and increasing urinary residuals.

Methods Women were recruited prospectively from a tertiary referral urodynamic clinic. All complained of troublesome lower urinary tract symptoms and underwent videocystourethrography including uroflowmetry, cystometry and pressure/flow voiding studies. Residual urine volumes were measured at catheterisation following uroflowmetry and again after the pressure/flow study. A residual of 100mls or greater on either occasion was taken to be significant. Urethral Pressure Profilometry (UPP) was performed in each case to exclude those women with voiding difficulties secondary to outflow obstruction. Those women with a urodynamic diagnosis of detrusor overactivity and a significant urinary residual were recruited to the study and commenced on antimuscarinic medication. Clinical assessment with a free urinary flow rate and ultrasound urinary residual was performed whilst taking medication at a scheduled follow up visit. All studies were performed in accordance with ICS Guidelines for Good Urodynamic Practice (2). Urinary symptoms and urodynamic parameters were analysed before and during antimuscarinic treatment using the Wilcoxon Signed Ranks test (SPSS, V10).

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Results In total 39 women were recruited to the study over an 18 month period. Mean age was 55 yrs (range 23 yrs – 82 yrs) and mean duration of follow up was 24 weeks (range 3 weeks – 306 weeks). All women had an objective diagnosis of detrusor overactivity with voiding difficulties; the urodynamic findings are shown below [Table1]. Antimuscarinic therapy was prescribed in keeping with unit protocol and at standard dose regimens (Tolterodine 2mg bd, Oxybutynin 2.5 – 5mg tds, Detrusitol XL 4mg od and Ditropan XL 10 – 30mg od.) [Table 2]. Urodynamic Diagnosis No (%) Systolic detrusor overactivity 7 (18) Provoked detrusor overactivity 12 (31) Provoked and systolic detrusor overactivity 9 (23) Low Compliance 12 (31) Detrusor overactivity and urethral sphincter incompetence 6 (15) Table 1: Urodynamic Diagnosis Antimuscarinic Drug No (%) Tolterodine (Immediate Release) 20 (51) Oxybutynin (Immediate Release) 8 (21) Tolterodine (Extended Release) - Detrusitol XL 8 (21) Oxybutynin (Extended Release) - Ditropan XL 3 (8) Table 2: Antimuscarinic Therapy Statistical analysis revealed a significant improvement in symptoms of urgency, frequency and nocturia with antimuscarinic therapy although there was no significant deterioration in symptoms of voiding difficulty, poor stream and recurrent lower urinary tract infection [Table 3]. In addition there was no significant decrease in urinary free flow rate or increase in residual volume whilst taking antimuscarinic medication [Table 4]. Lower urinary Tract Symptoms Pre- Treatment (%) Post–Treatment (%) p value Urgency 92 44 0.000 Frequency 74 30 0.000 Nocturia 69 30 0.000 Voiding Difficulties 21 15 0.414 Poor Stream 13 5 0.257 Recurrent Urinary Infection 8 10 0.655 Table 3: Lower Urinary Tract Symptoms before and during anti-muscarinic therapy Urodynamic Parameters Pre- Treatment Post -Treatment p value Mean free flow rate (mls/s) 14.0 17.7 0.057 Mean urinary residual (mls) 96 63 0.289 Table 4: Urodynamic Findings before and during anti-muscarinic therapy Conclusions To the best of our knowledge this is the first study to investigate the effect of anti-muscarinic therapy in women with detrusor overactivity and mild voiding difficulties. It is reassuring that despite significantly improving symptoms of an overactive bladder there appears to be no increase in symptoms such as recurrent lower urinary tract infections or slow stream which are suggestive of worsening voiding difficulties. In addition objective testing shows no evidence of diminished urinary flow rates and increasing residual volumes in those women taking anti-muscarinic therapy. This study provides reassurance that prescribing anti-muscarinics to women with detrusor overactivity and concomitant mild voiding difficulties is safe and there is no requirement to monitor residuals if the women themselves remain asymptomatic. References 1. BJU Int 1999; 84: 923 2. Neurourol Urodyn 2002; 21 (3): 261.

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123 Ashton-Miller J A1, Lien K1, DeLancey J1 1. University of Michigan PELVIC FLOOR SOFT TISSUE STRETCH INDUCED BY VAGINAL BIRTH Aims of Study Vaginal birth is known to increase the risk for pelvic organ prolapse (for example, Mant 1997) and urinary incontinence (for example, Hunskaar 2003). We hypothesize that maternal soft tissue injury may be implicated. Soft tissue injury can occur, for example, when tissue stretch exceeds an ultimate permissible value or similarly, when tissue shear or compression exceeds given limits. The values of maternal tissue stretch engendered by human vaginal birth are presently unknown. It therefore seems worthwhile to estimate soft tissue stretch during vaginal birth in order to identify the structures most at risk for stretch injury. We had two aims: Aim 1 was to develop a computer model of the soft tissues comprising the female human pelvic floor; Aim 2 was to use this model to simulate soft tissue stretch during the second stage of vaginal birth. We tested the null hypothesis that pelvic muscle tissue stretch is uniform during vaginal birth. Methods Thirty consecutive 5 mm-thick axial MR scans were obtained using a 1.5 T scanner from a healthy 34 year-old nulliparous woman who gave informed consent. The outlines of the bony pelvis, pelvic floor muscles and organs were digitized and imported into an engineering graphics program (IDEASTM). The outlines were lofted to yield a 3-D model of the female pelvis and pelvic floor. Twenty four 1 – 5 mm-thick and 5 - 10 mm-wide parallel-fibered muscle bands were used to represent the iliococcygeus, pubococcygeus, and puborectalis muscles on the left and right sides. Muscle fiber directions were taken from the literature. The arcus tendineii, perineal membrane and midline anococcygeal raphe were also represented. The fetal head was represented by a sphere of equivalent diameter that of a 50th percentile fetal head at 42 weeks of gestation. Using data from the literature, fetal head molding was simulated by considering that diameter to be reduced by 20% during the second stage of labor. Fetal head descent during the second stage of labor was then simulated by the incremental progression of the head along the Curve of Carus, as it descended around the pubic symphysis and progressively engaged and stretched the pelvic floor muscles. The maximum stretch ratio, defined as maximum stretched length divided by initial length, of each muscle band was then calculated at the end of the second stage of labor. Results The nulliparous pelvic floor computer model is shown in Figure 1 in a left-ventral (and slightly caudad) three-quarter exterior view. In that figure the upper view shows the intact model, while the lower view shows the detailed soft tissue anatomy of the pelvic floor with the pubic rami in outline. The “U-shaped” pubovisceral muscles are shown as they originate from the inner surface of the pubic bone on either side of the midline and insert into the perineal membrane, perineal body, and anal sphincter complex, as well as forming a sling behind the rectum. In the lower figure the muscle bands are numbered sequentially from 1 (puborectalis), 2 (ventral-most pubococcygeus band), to 24 (dorsal-most iliococcygeus band) in a ventrodorsal direction. The arcus tendinei appear as white bands, as does the midline anococcygeal raphe. The results for Aim 2 led us to reject the hypothesis that pelvic floor tissue is uniform during the second stage of labor. The maximum soft tissue stretch, 3.26, was found to occur in the medial-most band of pubococcygeus (marked as “2” in the lower illustration in Figure 1, see also Figure 2). This stretch ratio exceeds by 217% the largest non-injurious stretch ratio (1.5 stretch ratio) tolerated by passive striated muscles of the torso or extremities in non-gravid mammals (for example, Brooks 1995). The initial and final lengths of each numbered muscle band are shown in the upper half of Figure 2, while the resulting stretch ratio for each muscle band stretch ratio is shown in the lower half of that figure. Because of its short initial and long final length, the most ventral and medial pubococcygeal muscle band exhibited the greatest stretch ratio. Despite some limitations, this graphical analysis circumvents the limitations of current analytical approaches to structural simulation, which are limited to stretch ratios of about 1.3. Partial validation for the model predictions comes from MR scans of the pelvic floor of women nine months post-partum. These images

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show atrophic pelvic floor muscle in the region corresponding to the model muscle bands placed under greatest stretch.

Figure 1: Views of the Figure 2: Initial and final muscle lengths (top), and Nulliparous Pelvic Floor stretch ratios (bottom) by muscle band (see Fig. 1). Model. Conclusions We conclude that the left and right most ventral and medial parts of the pubococcygeal muscles undergo the largest pelvic floor tissue strains during vaginal birth. They may therefore be placed at the greatest risk for stretch-related injury during the second stage of labor. 124 Sampselle C M1, Miller J M1 1. University of Michigan School of Nursing URINARY INCONTINENCE DURING PREGNANCY PREDICTS POSTPARTUM UI MORE EFFECTIVELY THAN TYPE OF DELIVERY (CESAREAN VS. VAGINAL) Aims of Study Despite recent focus on Cesarean as protective of the pelvic floor, conflicting research asserts that genetic endowment and pregnancy are more important risk factors in postpartum UI (1,2). Our study assessed the relative capacity of antenatal UI and delivery type (Cesarean vs. vaginal) to predict postpartum UI. Methods An initial sample of 130 (98 at delivery) primigravidas with negative history of pre-pregnancy UI and no demonstrable UI at 20 weeks gestation were followed to 12 months postpartum. At each data point response to questions were used to construct the Leakage Index (LI)(3). The LI has demonstrated internal consistency (Chronbach’s alpha .72 to .84) and quantifies UI severity from 0 (no leakage) to 8 (positive report on all items). Delivery type was ascertained by medical record review. Pearson correlations were calculated for LI 35-week and LI at each postpartum data point. Finally, stepwise regression, entering LI 35-week first and then Delivery Type was conducted to identify the best predictive model at each postpartum point.

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Results Overall LI scores were in the lower range, regardless of delivery type (Table 1). Women who delivered vaginally had higher LIs compared to those who delivered by Cesarean section. Table 1. Leakage Index Scores Over Time and By Delivery Type 20 week gestation

35 week gestation

6 week postpartum

6 month postpartum

12 month postpartum

n Mean (sd)

n Mean (sd)

Delivery Type

n Mean (sd)

n Mean (sd)

n Mean (sd)

130 1.5 (1.9)

98 2.3 (2.1)

C-section

Vaginal

25

71

.07 (1.0)

1.8 (2.4)

p=.022*

25

65

0.6 (1.3)

1.9 (1.8)

p=.002*

20

62

0.6 (1.3)

1.7 (2.0)

p=.023*

*Two sample t-test Correlations of LI with postpartum outcomes (Table 2) demonstrated both LI 35-week and delivery type to be significant predictors of postpartum LI when considered in isolation.

Table 2. Correlation of 35 Week Leakage Index with Postpartum Outcomes Leakage

Index 35 weeks PERL1+

Leakage Index 6 weeks ppPERL1+

Leakage Index 6 months pp PERL1+

Leakage Index 12 months pp PERL1+

Method of Delivery

Leakage Index 35 weeks PERL1+

Pearson Correlation Sig. (2-tailed) N

1 98

.317** .002

89

.447** .000

84

.567** .000

74

-.240* .019 95

Leakage Index 6 weeks pp PERL 1+

Pearson Correlation Sig. (2-tailed) N

.317**

.002 89

1 98

.604** .000 85

.538** .000 75

-.234*.022

96

Leakage Index 6 months pp PERL1+

Pearson Correlation Sig. (2-tailed) N

.447**

.000 84

.604** .000 85

1 92

.725** .000 78

-.327** .002

90

Leakage Index 12 months pp PERL1+

Pearson Correlation Sig. (2-tailed) N

.567**

.000 74

.538** .000 75

.725** .000 78

1 83

-.252* .023

82

Method of Delivery

Pearson Correlation Sig. (2-tailed) N

-.240* .019

95

-.234**.022

96

-.327** .002

90

-.252* .023

82

1 113

**Correlation is significant at the 0.01 level (2-tailed) * Correlation is significant at the 0.05 level (2-tailed)

However, results of stepwise multiple regression indicated that the most predictive model of LI at each postpartum point was LI 35-weeks (Table 3). That is, elimination of delivery type from the equation improved the fit. Table 3. Stepwise Regression Results for Postpartum Leakage Predicted Leakage 6 weeks postpartum=.661 + .341 (LI 35-weeks) p<.05 R2=.10 (n=89) Delivery type eliminated from the equation t=-1.7, p=.097 Predicted Leakage 6 months postpartum=.642 + .377 (LI 35-weeks) p<.05 R2=.20 (n=84) Delivery type eliminated from the equation t=-2.0 p=.055 Predicted Leakage 12 months postpartum=.267 + .514 (LI 35-weeks) p<.05 R2=.32 (n=74) Delivery type eliminated from the equation t=-0.92, p=.363

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Conclusions These findings add to the evidence base that antenatal UI severity, not vaginal birth, is the primary predictor of postpartum UI. Hereditary factors and pregnancy pelvic floor stress clearly signal women’s risk of childbearing related UI prior to labor and delivery. The consistent pattern of 35-week gestation UI severity as a significant predictor of UI severity at all postpartum data points and the failure of delivery type to enhance the predictive capacity of the model underscores the robustness of this relationship. In light of these findings it is recommended that current attention to Cesarean on demand be shifted to more vigorous provider advocacy of behavioral strategies that have demonstrated a preventive effect for postpartum UI(4). References 1. King J, Freeman R (1998). Is antenatal bladder neck mobility a risk factor for postpartum stress

incontinence? British Journal Obstetrics & Gynecology, 105:1300-07. 2. Dimpfl T, et al. (1992). Incidence and cause of postpartum urinary stress incontinence. European

Journal of Obstetrics, Gynecology, and Reproductive Biology; 43:29-33. 3. Antonakos C, et al. (2003). Indices for studying urinary incontinence and levator ani function in

primiparous women. Journal of Clinical Nursing, 12:1-8. 4. Morkved S, et al. (2003). Pelvic floor muscle training during pregnancy to prevent urinary

incontinence: A single-blind randomized controlled trial. Obstetrics & Gynecology, 101:313-9. 125 Balmforth J1, Toozs-Hobson P2, Cardozo L1 1. Kings College Hospital, London, UK, 2. Birmingham Womens Hospital, Birmingham, UK ASK NOT WHAT CHILDBIRTH CAN DO TO YOUR PELVIC FLOOR BUT WHAT YOUR PELVIC FLOOR CAN DO IN CHILDBIRTH. Aims of Study The interaction between pregnancy, mode of delivery and pelvic floor function is controversial. There is robust evidence to suggest a significant association between mode of delivery and both the prevalence of subsequent urinary incontinence [1], and changes to dynamic pelvic floor anatomy assessed by ultrasound [2]. This study aims to explore the hypothesis that the inherent constitutional quality of a woman’s connective tissue influences the likelihood of normal progress in labour and the development of later pelvic organ prolapse and stress incontinence. By demonstrating antenatal differences in the functional anatomy of women who subsequently deliver by different routes, it supports the idea that mode of delivery may not be directly causative in determining the risk of pelvic floor dysfunction. Rather, the biomechanical qualities of pelvic floor connective tissue, which are known to be associated with pelvic floor dysfunction [3], may act as a confounding factor.

Methods Women in the 3rd trimester of their first ongoing pregnancy were recruited from a teaching hospital antenatal clinic and obstetric ultrasound department. Pelvic ultrasound assessment was performed by a single trained operator, using the same Kretz® Combison 530 ultrasound machine. The women were placed in a modified lithotomy position with a comfortably full bladder and assessed using a 7.5 MHz mechanical sector probe to image bladder neck position at rest, bladder neck rotation from its position at maximum pelvic floor squeeze to maximum excursion at valsalva [4] and levator hiatus area at squeeze, rest and valsalva. A three-dimensional transvaginal ultrasound was performed with a 3-D 7.5 MHz probe, in order to calculate rhabdosphincter and total urethral sphincter volume. The distribution of these ultrasonically measured parameters was examined and analysed using the Kolmogorov-Smirnov test. They were found to be normally distributed. Parametric statistical tests were therefore used to compare the ultrasound parameters of women who delivered vaginally with those who laboured but went on to have an emergency caesarean section.

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Constitutional Risk Factor

Inherent physical qualities of

connective tissue

Likelihood of normal progress

in labour

Mode of delivery

Development of subsequent

prolapse/stress incontinence

U/S parameters of pelvic floordistensibility

Deficit of published studies

Evidence exists

Evidence exists

Results 10 of the 98 women who underwent 3rd trimester antenatal assessment were delivered by pre-labour, elective caesarean section and these data were not included in the subsequent analysis. Of the 88 women who went into labour, 67 (76%) were delivered vaginally and 21 (24%) by emergency caesarean section. The majority of these were for failure to progress or fetal distress. The mean age of the vaginal delivery group was 29.7 years with a range of 18 to 41; the mean age of the caesarean section in labour group was 31.6 years with a range of 26 to 37. Maternal age, height, weight, mean birthweight, and gestation at delivery were not statistically different between these two groups of women. Table 1: Differences in antenatal 3rd trimester pelvic ultrasound parameters between women who subsequently delivered by vaginal delivery and emergency caesarean section

Antenatal values (mean +/- 1 sd)

vaginal delivery group vs c-section group

U/S parameter Vag. delivery (n=67)

C-section (n=21) Mean diff P value

Bladder neck at rest (degrees) 92.5 (19.2) 98.6 (14.3) +5.93 0.141 Bladder neck rotation* (degrees) 51.4 (23.3) 36.0 (15.7) -15.3 0.001 Levator hiatus areavalsalva (cm2) 17.6 (3.21) 16.1 (2.70) -1.47 0.046 Levator hiatus arearest (cm2) 15.0 (2.63) 14.4 (1.96) -0.553 0.305 Levator hiatus areasqueeze (cm2) 13.6 (2.08) 13.5 (1.61) -0.034 0.938 Rhabdosphincter volume (cm3) 0.98 (0.24) 1.09 (0.48) +0.114 0.306 Total sphincter volume (cm3) 2.11 (0.50) 2.18 (0.59) +0.060 0.601

*rotation=angular rotation from position at max. pelvic floor contraction to max. excursion on valsalva There are no significant differences in the static anatomical parameters between the groups. However, there are significant differences in bladder neck rotation and levator hiatus area at valsalva, the two dynamic ultrasound parameters that best reflect pelvic floor distensibility.

Conclusions The observable differences in the mechanical distensibility of the pelvic floor in these two groups of nulliparous women, suggest a fundamental difference in tissue qualities prior to delivery. These inherent biomechanical properties may play a role in determining the outcome of labour and also in the development of subsequent prolapse and stress incontinence. Further investigation is undoubtedly needed into the complex relationship that exists between the ‘quality’ of the connective tissues that support the pelvic viscera, the influence that these exert on the progress of labour, and the negative effect that different modes of delivery may have on the pelvic floor and its consequent function.

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Fig 1: Summary of differences in dynamic measures of pelvic floor anatomy in the two groups

V ag in al d e livery C aes arean sec tio n

B lad d er n eck ro tatio n

(S q u eez e to va lsa lva)

L evato r h ia tu s area

a t m axim u m valsa lva

excu rs io n

P =0 .001

P =0 .046

17 .6 cm 2

+ /- 3 .216 .1 cm 2

+ /- 2 .7

51 .4 o + /- 23.3 36 .0 o + /- 15.7

References Br J Obstet Gynaecol 1996; 103: 154-161. Neurourol Urodyn 2002; 21: 361. Br J Obstet and Gynaecol 1997; 104: 994-998. Br J Obstet Gynaecol 1997; 104: 1004-1008. 126 DeLancey J1, Kearney R1, Umek W1, Ashton-Miller J A1 1. University of Michigan LEVATOR ANI MUSCLE STRUCTURE AND FUNCTION IN WOMEN WITH PROLAPSE COMPARED TO WOMEN WITH NORMAL SUPPORT Aims of Study It has been hypothesized that damage to the levator ani muscles is associated with pelvic organ prolapse. The relative magnitude of this association and the degree of muscle damage and weakness, however, is unknown. This study was undertaken to test the null hypothesis that the levator ani muscles of women with symptomatic pelvic organ prolapse have the same 1) function and 2) structure as women with normal support (controls). In addition, we sought to evaluate whether the severity of levator ani muscle damage is different in the two groups. Methods We recruited 2 groups of women who signed informed consent to participate in this IRB approved study. Cases (n=102) were women with symptomatic pelvic organ prolapse (“Prolapse”) where the cervix or vaginal wall descended at least 1 cm below the hymenal ring using the POP-Q system. Controls (n=110) were asymptomatic women matched for age with no point of the vaginal wall or cervix lower than 1 cm above the hymen (Table). (N.B. Women with descent between these points were not included because experts differ in their opinion of whether they have prolapse or not.)

542

64

24

1419 22

57

0

10

20

30

40

50

60

70

None Minor Major

ControlProlapse

Women with prior surgery for pelvic floor dysfunction were excluded from the study. The increase in force generated by the levator muscle during maximum pelvic muscle contraction was recorded using an instrumented vaginal speculum in Newtons (N). Multiplanar proton density MRI scans at 5 mm intervals in the supine position were performed. The degree of muscle loss in the pubococcygeal portion of the levator ani muscle was quantified separately for the left and right muscle by examiners blinded to the subject’s clinical findings. A scale from 0 to 3 was used for each muscle with 0 representing no muscle loss and 3 representing complete loss of the pubococcygeal portion of the levator ani muscle. Scores for the left and right muscle were summed resulting in a possible combined score from 0 to 6. The degree of muscle loss was classified as follows: 0 = none, 1 to 3 = minor, 4 to 6 = major. Results Women with pelvic organ prolapse generated 43% less maximum levator ani force than controls (p<0.05) (Table). The graph shows the percentage of women in each group with no levator loss (“none”), minor loss and major loss. Women with prolapse were 2 .5 times more likely to have major loss of the pubococcygeus than controls. The reverse was true for those with no damage. Women with minor loss were the same in both groups.

Conclusion Women with pelvic organ prolapse are 2.5 times more likely to have major levator ani muscle loss and generate 43% less force during a maximal pelvic muscle contraction than age matched women with normal support. Comment: Earlier studies have identified that this type of levator ani muscle damage occurs as a result of vaginal birth [1]. This report links this birth-related damage to pelvic organ prolapse. References 1. The appearance of levator ani muscle abnormalities in magnetic resonance images after vaginal delivery. Obstet Gynecol 2003;101:46-53. 127 Dumoulin C1, Lemieux M 2, Bourbonnais D 1, Morin M 1 1. Université de Montréal, 2. Université McGill CONSERVATIVE MANAGEMENT OF STRESS URINARY INCONTINENCE: A SINGLE-BLIND, RANDOMIZED CONTROLLED TRIAL OF PELVIC FLOOR REHABILITATION WITH OR WITHOUT ABDOMINAL MUSCLE REHABILITATION COMPARED TO THE ABSENCE OF TREATMENT. Aims of Study Systematic review of randomized control trials suggests pelvic floor rehabilitation is an effective treatment for stress urinary incontinence (SUI) in women (1). However, recent data show that specific abdominal exercises may potentially be used to enhance pelvic floor rehabilitation (2). In addition, preliminary evidence reveals that specific abdominal exercises can effectively activate pelvic floor muscles in healthy subjects (2). In this context, it seems relevant to conduct a randomized controlled trial in order to study the

Mean (SD)

Prolapse n=102

Control N=110

Age in years 57.1 (12.5) 55.2 (12.7) Parity 3.1 (1.8) 2.4 (1.5) BMI 26.4 (5.0) 26.5 (4.8) LA Force (N) 2.1 (1.5) 3.7* (2.3)

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efficacy of a pelvic floor rehabilitation program with or without abdominal muscle training. The trial was designed to compare these two conservative treatments with a no-treatment condition in SUI women. Methods Sixty-two women (22-44 years: mean 35 years) with symptoms of stress urinary incontinence, including >1 urinary incontinence episode a week, were recruited from a gynecology clinic. Conventional urodynamic studies and a pad test assessment were conducted to confirm the subjects’ eligibility. Women were excluded if they showed involuntary detrusor contractions during filling cystometry, experienced perineal pain, vaginismus or excessive vaginal scarring that interfered with evaluation and treatment, had undergone previous uro-gynecology surgeries, presented important organ prolapse (>2 degrees Pop-Q) and had any uncontrolled medical problems that could interfere with treatment and evaluation (e.g. cardiovascular disease, neurological or psychiatric disease, cancer, or urinary or vaginal infection). Women were stratified for parity and severity of incontinence according to the pad test, then randomized to pelvic floor rehabilitation (n =20), pelvic floor rehabilitation with abdominal muscle training (n =23) and absence of treatment (n =19). Both treatment groups had a pelvic floor or pelvic floor/abdominal exercise program to do at home, once a day, five days a week, in addition to a physiotherapy session once a week over a period of eight weeks. Each physiotherapy session for the pelvic floor rehabilitation group consisted of a 15-min period of electrical stimulation followed by a 25-min pelvic floor exercise program (3). In addition, the abdominal muscle group had a 10-min session of deep abdominal muscle exercises. The third group had shoulder and back massage sessions of comparable duration (1 session/week x 8 weeks). The women in this third group were further randomized to one of the other groups as soon as their participation in the control group ended. A blinded outcome assessor took pre- and post-treatment measurements. Primary outcome measures consisted of a 20-min pad test with standardized bladder volumes. Secondary outcome measures included a global assessment of patient satisfaction using a visual analog scale (VAS), the Urogenital Distress Inventory (UDI) questionnaire and the Incontinence Impact Questionnaire (IIQ). Results The characteristics of the three groups in terms of age, parity and BMI were comparable at baseline. Furthermore, the outcome measures at baseline were not significantly different between the three groups. Pad test scores as well as VAS, UDI and IIQ scores improved significantly (all p< 0.02) in both treatment groups but not in the control group. Statistical analyses to detect significant differences in difference scores (pre-post scores) across groups was performed using the Kruskal-Wallis test. The Mann-Whitney test was then used to detect differences between paired groups. There were statistically significant differences between the three groups for all outcome measures (all p< 0.03). In addition, there were statistically significant differences for all outcome measures in two paired groups; control vs pelvic floor exercise (all p< 0.03) and control vs pelvic floor abdominal/exercise (all p< 0.02). However, no statistically significant differences between the treatment groups were detected for pad test scores (Mann-Whitney U= 217; p=0.751), VAS (p=0.75), UDI (p=0.81) and IIQ (p=0.35). Even after randomly reassigning the control group patients to one or the other of the experimental groups and thereby increasing the number of subjects in both groups (n =28, n =29), no statistically significant differences between the two treatment groups were detected in pad test scores (Mann-Whitney U= 343,5; p=0.318), VAS (p=0.62), UDI (p=0.61) and IIQ (p=0.41). Conclusions The results clearly indicate that conservative physiotherapy treatments are more effective than the absence of treatment in women with stress urinary incontinence. However, the addition of abdominal training did not further improve outcome of pelvic floor rehabilitation. References 1. Hay-Smith EJC et al. In: The Cochrane Library, Issue 4, 2002. 2. Sapsford RR et al. Co-activation of the abdominal and pelvic floor muscles during voluntary exercises. Neurourol Urodyn 2001;20 (1): 31-42. 3. Pelvic floor rehabilitation part II: Pelvic floor reeducation with interferential currents and exercise in the treatment of genuine stress incontinence in post-partum women; a cohort study. Physical Therapy, 1995;dec.: 43-49.

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128 Sampselle C M1, Messer K L2, Herzog R2, Hines S J1, Karl C 3, Diokno A A3 1. University of Michigan School of Nursing, 2. Univeristy of Michigan Institute for Social Research, 3. Beaumont Health System, Royal Oak, MI GROUP TEACHING OF PELVIC FLOOR AND BLADDER TRAINING: FUNCTION AND KNOWLEDGE OUTCOMES Aims of Study Conservative treatment of women with urinary incontinence, specifically pelvic floor training (PFT) and bladder training (BT) are recognized effective therapies(1). The conventional approach in teaching these behavioral therapies is individualized instruction followed by several visits to reinforce knowledge and technique. Only three published reports of a single session group education were identified, but none assessed improvement of pelvic floor contraction strength, an expected outcome of PFT, or lengthening of inter-void interval, an expected outcome of BT(2,3,4). This randomized controlled trial aimed to compare changes in pelvic floor contraction strength and inter-void interval at twelve months post intervention between women who attended a single group teaching session followed up with a single brief individual visit and those who did not. We further examined the treatment group’s knowledge of PFT and BT as well as adherence. Methods Volunteers who qualified from telephone screening were randomly assigned to a control no treatment group or to a treatment group that received the Behavioral Modification Program (BMP). Both groups underwent clinical baseline screening and evaluation of pelvic floor contraction strength (measured by palpation of pressure and displacement), and documentation of inter-void interval (measured by three-day voiding diary). The treatment group received a two-hour classroom presentation of the anatomy and physiology of continence, and rationale and verbal instruction in PFT and BT. This was followed in two to four weeks with an individualized evaluation to test knowledge (measured by response to eight multiple-choice items), technique (measured by palpation) and adherence (measured by report of practice). Brief additional instruction in PFT and BT was provided as needed. Follow-up was by phone and mail every three months except at the 12th month when all participants underwent a final clinical examination. Treatment versus control group changes in pelvic floor strength and inter-void interval were assessed by Chi Square, paired-t, and with multiple regression to control for age, race, education, and baseline status. Results A total of 195 control and 164 treated participants completed the study. Group equivalence at baseline was evident in the lack of statistical difference for age (mean age 65.8 years), race (82% White), education (80% greater than high school), or medical history and for pelvic floor contraction pressure, displacement, and inter-void interval. In the treatment group at two to four weeks post instruction mean knowledge was 87% for PFT and 89% for BT. Palpation of PFT technique revealed 68% needing no further instruction, 32% requiring brief individual instruction (approximately 5 minutes), and 3% unable to demonstrate effective pelvic floor contraction techniques after individual instruction and excluded from the study. With respect to adherence participants in the BMP were encouraged to practice PFT every day throughout the 12-month post instruction period. At the 3-month data point 82% reported practicing PFT two to three or more times per week. By the 12-month exit point 68% continued to practice PFT two to three or more times per week. At the 12-month exit the treatment group as compared to control counterparts demonstrated significant increases in pelvic floor contraction pressure and displacement (p=.0008 and p<.0001, respectively). Inter-void interval also demonstrated significant lengthening at the 12-month exit point for those in the BMP group as compared to the control group (p<.0001). A regression model that adjusted for UI level at baseline and other covariates including race, age, and education, revealed a treatment group effect that was significant at p< .0001 for each of the three outcomes: pelvic floor contraction pressure, displacement, and inter-void interval.

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Conclusions This RCT of the effectiveness of group teaching of behavioral therapies followed by brief individual instruction as needed demonstrated positive effects on knowledge, technique, and adherence. The significant 12-month outcome differences between treatment and control groups provide evidence that group instruction in PFT and BT with brief training as needed is an effective method to teach these behavioral therapies. Clearly, the necessary knowledge and skills were imparted to enable women to perform PFT and BT at levels that resulted in significant differences in pelvic floor contraction strength and lengthened inter-void interval. The greater efficiency of instruction when provided to groups rather than individually warrants further study to document cost-effectiveness outcomes. References

1. Wilson PD, Bo K, Hay-Smith J, Nygaard I, Staskin D, & Wyman J. (2002). Conservative treatment in women. In Abrams, Cardozo, Khoury, and Wein (Eds) Incontinence, 2nd Edition. Plymouth, UK: Plymbridge Distributors Ltd.

2. Girard L. (1997). Group learning behavior modification and exercise for women with urinary incontinence. Urological Nursing, 17(1):17-22.

3. McFall SC, Yerkes AM, Cowan LD. (2000). Outcomes of a small group educational intervention for urinary incontinence: episodes of incontinence and other urinary symptoms. Journal of Aging and Health, 12(2):250-67.

4. Jansson CC, Lagro-Janssen AL, Felling AJ. (2001). The effects of physiotherapy for female urinary incontinence: individual compared with group therapy. British Journal of Urology International, 87(3):201-6.

129 Naumann G1, Hentschel B2, Höckel S3, Höckel M3 1. Dep. of Gynecology, University Halle-Wittenberg, Germany, 2. Institute of Medical Informatics, Statistics and Epidemiology, University Leipzig, Germany, 3. Dep. of Obstetrics and Gynecology, University of Leipzig, Germany PROSPECTIVE EVALUATION OF URETHRO-VESICAL, VULVO-VAGINAL AND ANO-RECTAL FUNCTION AFTER TOTAL MESOMETRIAL RESECTION (TMMR) IN CERVICAL CANCER Aims of Study Damage of the pelvic autonomic nerve system at various sites during Wertheim-Meigs radical hysterectomy may lead to postoperative long-term impairment of pelvic visceral functions. We developed total mesometrial resection (TMMR) with extended pelvic/periaortic lymph node dissection not only to improve oncological and functional outcome in patients with early stage cervical cancer. One feature of this novel surgical procedure is the exposure and preservation of the essential parts of the autonomic nerve system supplying the pelvic viscera at the sites of resection. Methods A prospective longitudinal study to evaluate urethrovesical, vulvovaginal and anorectal function of patients undergoing TMMR was carried out with assessment of pre-, and postoperative (at 3, and at 12 months) symptoms using a standardised questionnaire, clinical and urogynecological investigations. From 7/1998 until 7/2002 71 patients with early stage cervical cancer were treated with TMMR. Pre- and postoperative urogynecological assessment comprised exclusion of urinary tract infection, residual urine measurements, uroflowmetry, filling cystometry, urethral pressure measurements (Andromeda, Unterhaching), a clinical stress test in the lying and supine position, and introital ultrasound (Toshiba). Forty-seven patients treated with TMMR during the first three years (7/98 – 7/01) were eligible for the prospective longitudinal evaluation of TMMR related disturbances of the lower urinary, genital and intestinal functions.

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Results 71 patients with cervical cancer stages (y)pT1b1 (n=48), (y)pT1b2 (n=8), pT2a (n=3), (y)pT2b (n=12) underwent TMMR without (neo)adjuvant radiation. Mean pathological tumor size was 2.7 ± 1.6 cm. Twenty percent of the patients had (y)pN1, 4% (y)pM1(LYM) stages. Fifty-four percent of the patients exhibited histopathological high risk factors. At a median observation period of 26 months two patients relapsed locally, two patients developed pelvic and distant and two patients only distant recurrences. Grade 1 and 2 complications occurred in 15 resp. 5 patients, no patient developed grade 3 or 4 complications. Clinical investigation revealed an increase in the number of patients with grade I stress incontinence from 5 of 31 preoperatively to 8 of 31 twelve months postoperatively. Three patients presented with residual urine >50 ml 12 months after TMMR treatment as compared to zero preoperatively. Maximum residual urine measured was less than 100 ml. The results were not statistically significant. Median residual urine volume increased from 10 ml to 21 ml after 3 months and 20 ml after 12 months (p = 0.007). Urodynamic testing showed no significant changes after TMMR treatment with respect to most of the parameters representing lower urinary tract function such as bladder compliance, detrusor pressure, urine flow rate and functional urethral length. However, statistically significant alterations were detected for bladder volume, voiding time and urethral closure pressure. The bladder volume at first desire to void increased from 279 ± 79 ml preoperatively to 355 ± 92 ml at one year postoperatively, the micturition time from 45 ± 17 sec to 56 ± 8 sec and the urethral closure pressure from 65 ± 20 cm H2O to 74 ± 20 cm H2O. For these parameters the pairwise comparisons preoperative with postoperative 12 months after TMMR were significant. One year after TMMR 3 of 25 patients experienced a reduced bladder filling sensitivity compared to one patient before the operation. Twelve patients voided with abdominal straining to empty their bladder completely one year after the operation, whereas this micturition aid was used only by 6 patients preoperatively. No marked changes in sensory urgency and nocturia became evident from the questionnaire investigation. More patients perceived reduced vaginal elasticity than reduced vaginal length as sequelae of the surgical treatment. Vaginal lubrication was not altered by TMMR according to the patients’ estimation. The relative number of sexually active patients after 12 months was the same as preoperatively. Treatment with TMMR did not lead to apparent alterations in anorectal functions according to the patients’ self estimation Conclusions The preliminary results of our prospective longitudinal study support the concept and feasibility of TMMR to expose and preserve pelvic autonomic nerves during extended radical hysterectomy and pelvic/periaortic lymph node dissection. Our study could not detect major postoperative disturbances of urethrovesical, vulvovaginal and anorectal functions related to autonomic innervation. Irrespective of the results with TMMR our prospective longitudinal study confirms the importance of preoperative investigation of patients with cervical cancer in order to evaluate therapy related effects on pelvic visceral functions. 130 Nieminen K1, Hiltunen K2, Laitinen J2, Oksala J2, Heinonen P2 1. University of Tampere, 2. Tampere University Hospital TRANSANAL OR VAGINAL APPROACH TO RECTOCELE REPAIR: RESULTS OF A PROSPECTIVE RANDOMISED STUDY Aims of Study Current opinion of treatment of rectocele advocates surgery. Gynecologists have treated rectocele with vaginal posterior colporrhaphy for over a century whereas coloproctologists use transanal route. Colorectal surgeons have focused on improvement of bowel function and gynecologists to restoration of anatomy when assessing results of rectocele repair. We performed a prospective, randomised study focusing on both anatomical results and relieve of symptoms.

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Methods Thirty women, 15 in both groups, with symptomatic rectoceles not responding to conservative treatment were enrolled in the study. Patients with compromised anal sphincter function or other symptomatic genital prolapse were excluded from the study.All the patients reported bowel symptoms for a two-week period, underwent interview with a standardised questionnaire, clinical examination as recommended by International Continence Society, colon-transit study, defecography and anorectal manometry both preoperatively and 12 months after surgery. Posterior colporrhaphy without plication of levator ani was performed by the same gynecologists and transanal surgery by an experienced coloproctologist. No concurrent operations were performed except treatment of enterocele in two patients undergoing vaginal surgery. Independent samples t-test was used for continuous data between the study groups and paired samples t-test to study differences between preoperative and follow-up measurements. Chi-square or Fisher’s exact tests were used for nominal or ordinal data and Wilcoxon signed rank test for differences between preoperative and follow-up symptoms. Results No significant differences were found preoperatively between the groups concerning demographic factors, previous operations or preoperative symptoms. Important outcomes are listed in Table 1. Table 1. Pre- and postoperative data of the 30 patients operated on for symptomatic rectocele. Vaginal surgery

n=15 Transanal surgery n=15

p-value

Depth of rectocele in defecography (cm)

Preoperative Follow-up p*-value

6.0±1.6 (3.0-8.0) 2.73±1.87 (0-6.0) 0.000

5.6±1.8 (3.0-8.5) 4.13±2.10 (0-9.0) 0.07

0.53 0.06

Value of point Ap Preoperative Follow-up p*-value

-0.10±0.74 (-1-1) -2.8±0.56 (-3- -1) p*=0.000

-0.03±0.67 (-1-1) -1.36±1.12 (-3-0) p*=0.000

0.29 0.01

Digitation Preoperative Follow-up p*-value

11 (73) 1 (7) 0.01

10 (66) 4 (27) 0.02

0.17

Improvement of symptoms 14 (93) 11 (73) 0.08 Posterior vaginal wall prolapse (all)

1 (7) 10 (67) 0.01

Rectocele 1 6 0.04 Enterocele 0 4 0.05

Values are mean±sd (range) or n (%) p*-value=paired samples t-test or Wilcoxon signed rank test, when appropriate, for the differences between the preoperative and follow-up measurements. Mean anal resting pressure -values did not differ between the groups, but values for transanal group were statistically significantly lower at follow-up compared to preoperative situation. Four patients (27 %) reported gas incontinence in transanal group whereas none in vaginal group, but the difference does not reach statistical significance (p=0.057). Six patients in vaginal and two in transanal group reported improvement of sexual life at follow-up; none reported de novo dyspareunia. Conclusions Improvement of symptoms and restoration of anatomy was seen in both groups. Vaginal approach showed superior results when assessed by clinical examination. In this study, transanal technique predisposed to recurrent rectocele and de novo enterocele. No adverse effects on sexual life were found. Transanal approach may compromise anal sphincter function.

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