Joint Meeting of the International Continence Society and the International UroGynecological Association, 34rd Annual Meeting, Paris, France, 25th–27th August 2004

ICS and IUGA 2004 387

SCIENTIFIC PROGRAMME Wednesday 25th August 2004 09:30 - 11:00 Session 1 Plenary Podium - Questionnaires and Epidemiology - Main Auditorium 09:30 1 DEVELOPMENT AND PSYCHOMETRIC EVALUATION OF THE ICIQ MODULES

Avery K, Abrams P, Chadwick M, Donovan J 09:45 2 A VALIDATED FEMALE PELVIC FLOOR QUESTIONNAIRE FOR CLINICIANS AND RESEARCHERS

Baessler K, O'Neill S, Maher C, Battistutta D 10:00 3 MEASURING PATIENT OUTCOMES IN OAB: THE OAB-Q, ICIQ OAB-Q SF AND SCREENER

Abrams P, Avery K, Zyczynski T, Kopp Z, Coyne K 10:15 4 DISTRIBUTION OF PELVIC ORGAN PROLAPSE (POP) IN THE GENERAL POPULATION; PREVALENCE,

SEVERITY, ETIOLOGY AND RELATION WITH THE FUNCTION OF THE PELVIC FLOOR MUSCLES. Slieker-ten Hove M C P, Vierhout M, Bloembergen H, Schoenmaker G

10:30 5 NATURAL HISTORY OF THE ACQUISITION OF NIGHT-TIME BLADDER CONTROL: TRACKING STUDY TO

FOLLOW CHILDREN FROM AGE 3 1/2 YEARS LIVING IN SCOTLAND Morison M, Staines H, Sullivan F, Wilson P, Stone D, Tappin D, Henderson M

10:45 6 A GENETIC LINKAGE STUDY OF DETRUSOR OVERACTIVITY

Morris A R, Mullan G, Roscioli T, Buckley M F, Moore K H 14:00 - 15:30 Session 2 Podium - Pregnancy & Delivery - Blue Room 14:00 7 THE CHOICE OF ELECTIVE CESAREAN DELIVERY IN OBSTETRICS: HOW DOES THE RISK OF PELVIC

FLOOR INJURY INFLUENCE CLINICAL DECISION-MAKING Farrell S, Baskett T , Farrell K

14:15 8 DELIVERY MODE IS THE MAJOR DETERMINANT OF STRESS URINARY INCONTINENCE IN PAROUS

WOMEN: ANALYSIS OF 288 IDENTICAL TWINS Goldberg R, Gandhi S, Abramov Y, Botros S, Nickolov A, Sherman W, Sand P

14:30 9 PREVALENCE AND RISK FACTORS FOR ANAL INCONTINENCE: NEW INSIGHT THROUGH AN IDENTICAL

TWIN SISTERS STUDY Abramov Y, Sand P K, Gandhi S, Botros S, Nickolov A, Sherman W, Goldberg R P

14:45 10 DOES PELVIC FLOOR MUSCLE TRAINING DURING PREGNANCY HAVE AN EFFECT ON LABOUR?

Morkved S, Salvesen K Å 15:00 11 A RANDOMISED TRIAL OF OVERLAP VS END-TO-END PRIMARY REPAIR OF THE ANAL SPHINCTER

Fernando R, Sultan A, Kettle C, Radley S, Jones P, O'Brien S 15:15 12 DIRECT END-TO-END OR OVERLAPPING DELAYED ANAL SPHINCTER REPAIR FOR ANAL

INCONTINENCE: LONG-TERM RESULTS OF A PROSPECTIVE RANDOMISED TRIAL Goh J, Carey M, Tjandra J

14:00 - 15:30 Session 3 Podium - Urodynamics - Maillot Room 14:00 13 THE NATURAL HISTORY OF DETRUSOR CONTRACTILITY: MINIMUM 10-YEAR URODYNAMIC FOLLOW

UP IN MEN WITH BLADDER OUTLET OBSTRUCTION AND THOSE WITH DETRUSOR UNDERACTIVITY. Al-Hayek S, Thomas A, Abrams P

14:15 14 VARIATION OF INVASIVE AND NON-INVASIVE MEASUREMENTS OF ISOVOLUMETRIC BLADDER

PRESSURE ACCORDING TO BLADDER VOLUME Harding C, Robson W, Drinnan M, Ramsden P , Griffiths C, Pickard R

14:30 15 DETRUSOR CONTRACTILITY IS GREATER IN MALE PATIENTS WITH DETRUSOR OVERACTIVITY

Belal M, Blake C, Harding C, McIntosh S, Griffiths C, Robson W, Drinnan M , Ramsden P, Pickard R, Abrams P © 2004 Wiley-Liss, Inc. DOI 10.1002/nau.20062


Session 3 (cont) 14:45 16 URODYNAMIC INTER-RATER RELIABILITY BETWEEN LOCAL AND CENTRAL PHYSICIAN REVIEWERS

FOR THE FILLING CYSTOMETROGRAM IN SISTER (STRESS INCONTINENCE SURGICAL TREATMENT EFFICACY TRIAL) Zimmern P, Nager C, Albo M, Fitzgerald M, Mohr B, McDermott S

15:00 17 RELIABILITY TESTING OF URETHRAL FUNCTION IN WOMEN WITH MIXED URINARY INCONTINENCE.

Rahmanou P, Chaliha C, Scholfield D, Skillern L, Khullar V 15:15 18 STRIATED URETHRAL SPHINCTER ACTIVITY IS NOT AFFECTED BY PELVIC ORGAN PROLAPSE

DESPITE CHANGES IN MAXIMAL URETHRAL CLOSURE PRESSURE. Mueller E, Kenton K, Mahajan S, Fitzgerald M P, Brubaker L

14:00 - 15:30 Session 4 Poster - Pelvic Floor Surgery - Main Auditorium 14:00 19 BIOMECHANICAL PROPERTIES OF MESHES

Krause H, Goh J, Forward M, Bennett M 14:07 20 BIOCOMPATIBLE PROPERTIES OF SURGICAL MESH USING AN ANIMAL MODEL

Krause H, Goh J, Khoo S K, Williams R, Galloway S 14:15 21 PRELIMINARY PROCEDURAL AND SAFETY DATA FROM THE UNITED STATES CLINICAL STUDY ON THE

AMS MONARC™ SUBFASCIAL HAMMOCK Moore R, Miklos J, Knoll L D, Dupont M, Winkler H A, Lind L, Kohli N, Serels S, Karram M, Walters M, Davila W

14:22 22 INSIDE-OUT TRANSOBTURATOR VAGINAL TAPE (TVT-O): SHORT-TERM RESULTS OF A PROSPECTIVE

STUDY Waltregny D, Reul O, Bonnet P, de Leval J

14:30 23 DOES TENSION CHANGES THE OUTCOME OF TVT? A PROSPECTIVE MULTICENTRE STUDY OF 809

PATIENTS. Schraffordt S, Bisseling T, Heintz P, Vervest H

14:37 24 MESH EROSION COMPLICATING VAGINAL SURGERY FOR THE CORRECTION OF POSTERIOR

COMPARTMENT PROLAPSE Birch C, Fynes M

14:45 25 LAPAROSCOPIC COLPOSUSPENSION OR TENSION-FREE VAGINAL TAPE FOR RECURRENT STRESS

URINARY INCONTINENCE AND OR ISD: A RANDOMISED CONTROL TRIAL. Maher C, Qatawneh A, Baessler K , Cropper M , Schluter P

14:52 26 LAPAROSCOPIC COLPOSUSPENSION VS VAGINAL MESH SLING: A RANDOMISED PROSPECTIVE TRIAL

Foote A, Carne C, Lowndes C

15:00 27 PORCINE DERMIS XENOGRAFT AS REINFORCEMENT FOR CYSTOCOELE STAGE III REPAIR: A

PROSPECTIVE RANDOMIZED CONTROLLED TRIAL De Ridder D, Claerhout F, Verleyen P, Boulanger S , Deprest J

15:07 28 CAN DISCRETE VAGINAL FASCIAL DEFECTS BE ACCURATELY IDENTIFIED PRE-OPERATIVELY?

Guerette N, Davila G W 15:15 29 DOES DISCRETE SITE-SPECIFIC DEFECT REPAIR OFFER BETTER OBJECTIVE OR SUBJECTIVE

OUTCOMES THAN STANDARD POSTERIOR COLPORRHAPHY? Abramov Y, Gandhi S, Goldberg R , Botros S, Kwon C, Sherman W, Sand P

15:22 30 HYSTERECTOMY; IS IT ESSENTIAL FOR THE CORRECTION OF UTERINE PROLAPSE?

Kim J, Kim T, Lim K, Joo K 16:00 - 17:00 Session 5 Poster - Lower Bowel Dysfunction - Main Auditorium 16:00 31 THE PREVALENCE OF RECTOVAGINAL FASCIAL DEFECTS IN YOUNG NULLIPARAE: CAN RECTOCELE

BE A CONGENITAL CONDITION? Dietz H P, Eldridge A , Grace M, Clarke B

16:07 32 WOMENS HEALTH, INCONTINENCE AND SEXUAL LIFE 18 YEARS AFTER AN ANAL SPHINCTER TEAR AT

CHILDBIRTH Faltin D, Otero M, Floris L, Sangalli M, Bianchi-Demicheli F, Vieille J, Weil A, Irion O, Boulvain M


Session 5 (cont) 16:15 33 OCCULT ANAL SPHINCTER INJURIES -- MYTH OR REALITY?

Andrews V, Thakar R, Sultan A 16:22 34 WOMEN WITH RECTAL OUTLET OBSTRUCTION HAVE ALTERED BLADDER FUNCTION

Balmforth J, Gladman M, Cardozo L, Williams N 16:30 35 WITHIN AND ACROSS SUBJECT REPRODUCIBILITY OF THE MULTI-ELECTRODE SURFACE EMG FROM

THE EXTERNAL ANAL SPHINCTER. Hinninghofen H, Liu M, Merletti R, Bottin A, Enck P

16:37 36 EFFECTS OF OVARIECTOMY AND HORMONE REPLACEMENT ON SUBMUCOSAL COLLAGEN AND

BLOOD VESSELS OF THE ANAL CANAL OF RATS Rizk D, Mensah-Brown E, Patel M, Chandranath S , Naseer O, Ahmed I, Al-Haj M, Adem A

16:45 37 MOSAPRIDE CITRATE, A NOVEL 5-HT4 AGONIST AND PARTIAL 5-HT3 ANTAGONIST, AMELIORATES

CONSTIPATION IN PARKINSONIAN PATIENTS Sakakibara R, Uchiyama T, Liu Z, Yamamoto T, Ito T, Yamanishi T, Hattori T

16:52 38 A BLINDED, SHAM-CONTROLLED TRIAL OF POSTPARTUM EXTRACORPOREAL MAGNETIC

INNERVATION TO RESTORE PELVIC MUSCLE STRENGTH IN PRIMIPAROUS PATIENTS Culligan P, Blackwell L, Murphy M, Ziegler C, Heit M

16:00 - 17:00 Session 6 Poster - Basic Science & Pharmacology - Blue Room 16:00 39 DIFFERENTIAL ROLES OF CENTRAL AND PERIPHERAL NITRIC OXIDE MECHANISMS IN THE

REGULATION OF LOWER URINARY TRACT FUNCTION IN THE RAT Masuda H, Chancellor M, Kihara K, de Groat W, Yoshimura N

16:07 40 AGE-RELATED DECREASE IN MUSCARINIC M3 BUT NOT M2 RECEPTOR MRNA IN THE MALE

DETRUSOR MUSCLE. Burcher E, Mansfield K J, Liu L, Vaux K J, Moore K H

16:15 41 THE EFFECT OF ACUTE OVARIECTOMY ON RABBIT BLADDER BLOOD FLOW AND OXYGEN TENSION

Levin R, Whitbeck C, Chichester P, Badger W 16:22 42 INCREASED GAP JUNCTION CONNECTIVITY AND FOCAL PACEMAKER ACTIVITY IN THE BLADDER

FOLLOWING SPINAL CORD INJURY MAY LEAD TO URINARY INCONTINENCE - REVEALED THROUGH OPTICAL IMAGING Hayashi F, de Groat W, Roppolo J, Birder L, Griffiths D, Tai C, Bergamin L, Wu H, Kanai A

16:30 43 EFFECTS OF TAMSULOSIN, AN ALPHA1-ADRENERGIC ANTAGONIST, AND TAK-802, A NOVEL

ACETYLCHOLINESTERASE INHIBITOR, AND THEIR SYNERGISTIC EFFECTS ON THE URODYNAMIC CHARACTERISTICS IN A GUINEA PIG MODEL OF FUNCTIONAL BLADDER OUTLET OBSTRUCTION Nagabukuro H, Hashimoto T, Iwata M, Ishihara Y, Doi T

16:37 44 EFFECTS OF 138-355, A BETA3-ADRENOCEPTOR SELECTIVE AGONIST, ON RELAXATION OF THE

HUMAN DETRUSOR MUSCLE IN VITRO Yamanishi T, Yasuda K, Kitahara S, Nakanishi K, Sakakibara R, Uchiyama T, Yoshida K, IIzuka H

16:45 45 DO ARTIFICIAL SWEETENERS AFFECT BLADDER CONTRACTION?

Dasgupta J, Elliott R, Tincello D 16:52 46 DECLINE OF SALIVARY MUSCARINIC RECEPTOR BLOCKING ACTIVITY OF PROPIVERINE

HYDROCHLORIDE BY THE LONG-TERM ADMINISTRATION Yamada S, Oki T, Sakakura K, Komoto I, Yoshida K, Kimura R

16:00 - 17:15 Session 7 Poster - Pelvic Floor Dysfunction & Male Urinary Disorder - Maillot Room 16:00 47 DOES YOUR BONY PELVIC SHAPE DETERMINE YOUR PELVIC SOFT TISSUE DESTINY? RESULTS OF A

3D MRI STUDY. Hoyte L, Jakab M, Shott S , Brubaker L

16:07 48 IS NOCTURNAL POLYURIA A KEY FACTOR IN NOCTURIA?

Abrams P, Mattiasson A , Van Kerrebroeck P, Robertson G 16:15 49 CORRELATION BETWEEN ALPHA1-ADRENORECEPTOR SUBTYPE MRNA EXPRESSION LEVEL AND

EFFICACY OF NAFTOPIDIL FOR BPH PATIENTS Kojima Y, Sasaki S , Kohri K, Shinoura H, Tsujimoto G


Session 7 (cont) 16:22 50 DETRUSOR OVERACTIVITY AND CONNEXIN EXPRESSION IN PATIENTS WITH BLADDER OUTLET

OBSTRUCTION DUE TO BENIGN PROSTATIC HYPERPLASIA Kim J C, Park E Y, Seo S I, Park Y H, Hwang T

16:30 51 IS EVALUATION OF URETHRAL OBSTRUCTION AND DETRUSOR FORCE POSSIBLE FROM COUPLING

OF DATA FROM ONE FREE UROFLOW AND ONE PENILE CUFF TEST IN PATIENTS WITH BENIGN PROSTATIC ENLARGEMENT (BPE)? PRELIMINARY STUDY Valentini F, Besson G , Nelson P

16:37 52 POSTPROSTATECTOMY INCONTINENCE: SIGNIFICANCE OF THE PRE-OPERATIVE URETHRAL

PRESSURE PROFILE AND THE ROLE OF PHYSIOTHERAPY Dubbelman Y D, Groen J, Bosch R

16:45 53 A RANDOMISED CONTROLLED TRIAL OF PELVIC FLOOR EXERCISES FOR POST-MICTURITION

DRIBBLE IN MEN WITH ERECTILE DYSFUNCTION Dorey G, Speakman M, Feneley R, Dunn C, Swinkels A , Ewings P

16:52 54 LONG-TERM EFFICACY, SAFETY AND QUALITY OF LIFE RESULTS OF SACRAL NEUROMODULATION

FOR THE TREATMENT OF VOIDING DYSFUNCTION’S: OUTCOMES FROM A PROSPECTIVE, WORLDWIDE CLINICAL STUDY van Voskuilen A, van Kerrebroeck P , van den Homberg U, Approval Study Group P

17:00 55 AUTOMATIC EVENT DRIVEN ELECTRICAL STIMULATION FOR TREATMENT OF NEUROGENIC

DETRUSOR OVERACTIVITY IN SPINAL CORD INJURED PATIENTS Hansen J, Fjorback M V, Media S, Nøhr M, Biering-Sørensen F, Sinkjær T, Rijkhoff N J M

17:07 56 CONDITIONAL ELECTRICAL STIMULATION OF THE DORSAL PENILE/CLITORAL NERVE FOR

MANAGEMENT OF NEUROGENIC DETRUSOR OVERACTIVITY IN MULTIPLE SCLEROSIS Voss Fjorback M, Rijkhoff N, Petersen T , Nohr M , Sinkjaer T

Thursday 26th August 2004 09:15 - 11:00 Session 8 Plenary Podium - Urodynamic Assessment - Main Auditorium 09:15 57 HOW DOES THE URINARY FLOW CLEAN THE URETHRA DURING THE MICTURITION? THE ROLE OF

LOW URINARY FLOW ON BLADDER OUTLET OBSTRUCTED PATIENTS. Freire M, Almeida F G, Cedenho A, Rosa A A , Srougi M , Bruschini H

09:30 58 PREDICTIVE VALUE AND SENSITIVITY TO CHANGE OF NON-INVASIVE PRESSURE FLOW STUDIES

Harding C, Robson W, Drinnan M, Ramsden P, Griffiths C, Pickard R 09:45 59 IS URETHRAL RESISTANCE A USEFUL CONCEPT?

Robinson D, Balmforth J, Cardozo L, Parsons M 10:00 60 DO SYMPTOMS OF OVERACTIVE BLADDER PREDICT URODYNAMICS DETRUSOR OVERACTIVITY?

Hashim H, Abrams P 10:15 61 RELATIONSHIPS BETWEEN BLADDER OUTLET OBSTRUCTION, BLADDER COMPLIANCE AND RENAL

FUNCTION IN ADULT MEN WITH LUTS Lewis J, Sullivan M, Nabha K, Bartolome V, Siroky M, Yalla S

10:30 62 CUT-OFF VALUES TO DEFINE BLADDER OUTLET OBSTRUCTION (BOO) IN WOMEN

biscotto S, costantini E, rociola W, mearini L, bini V, porena M 10:45 63 SYSTEMATIC REVIEW AND EVALUATION OF METHODS OF DIAGNOSTIC ASSESSMENT FOR URINARY

INCONTINENCE. Williams K, Martin J, Abrams K, Assassa R P, Chapple C, Shaw C , Turner D, Sutton A, Cheater F

14:00 - 16:00 Session 9 Podium - Pelvic Floor Surgery - Main Auditorium 14:00 64 A LONGITUDINAL MORPHOLOGICAL EVALUATION OF THE HOST RESPONSE TO TWO COLLAGEN

BASED AND ONE POLYPROPYLENE IMPLANTS IN A RABBIT MODEL FOR ABDOMINAL WALL HERNIA. CLAERHOUT F, DE RIDDER D, VERBEKEN E, DEPREST J

14:15 65 IS THE COUGH TEST NECESSARY? A CASE CONTROL SERIES OF TWO TECHNIQUES OF TVT

ADJUSTMENT Barry C L, Dietz H P, Rane A, Wilson P D


Session 9 (cont) 14:30 66 MULTICENTER RANDOMIZED TRIAL OF TENSION-FREE VAGINAL TAPE (TVT) AND INTRAVAGINAL

SLINGPLASTY (IVS)FOR THE TREATMENT OF STRESS URINARY INCONTINENCE IN WOMEN Pifarotti P, Meschia M, Gattei U, Bernasconi F, Magatti F, Viganò R

14:45 67 THE SUBURETHRAL SLINGPLASTY EVALUATION STUDY IN NORTH QUEENSLAND (SUSPEND): A

RANDOMIZED CONTROLLED TRIAL Lim Y N, Rane A, Barry C, Corstiaans A, Dietz H P, Muller R

15:00 68 CHANGES OF THE LOWER URINARY TRACT AFTER SUCCESFUL TVT OPERATION-ULTRASOUND

STUDY Masata J, Martan A, Svabik K, Drahoradova P, Halaska M, Pavlikova M, Hlasenska J

15:15 69 GROIN PAIN FOLLOWING TENSION FREE VAGINAL TAPE( TVT ): MANAGEMENT STRATEGIES

Jain S, Duckett J 15:30 70 EXPEDIENCY OF UROGENITAL PATHOLOGY CORRECTION COMBINED WITH ABDOMINOPLASTY IN A

PLASTIC SURGERY CLINIC. Piskunova E, Golubkov N

15:45 71 VAGINAL PARAVAGINAL REPAIR USING PORCINE OR HUMAN CADAVERIC DERMAL GRAFT: A

SURVIVAL ANALYSIS Arya L, Novi J, Clemons J, Myers D

14:00 - 16:00 Session 10 Poster - Neurourology Basic Science - Blue Room 14:00 72 REGENERATION OF HYPOGASTRIC NERVE USING A POLYGLYCOLIC ACID(PGA)-COLLAGEN NERVE

CONDUIT FILLED WITH COLLAGEN SPONGE PROVED ELECTROPHYSIOLOGICALLY IN A CANINE MODEL Suzuki K, Ukimura O, Ushijima S, Hirahara N, Itoh T, Hagiwara A, Nakamura T, Shimizu Y, Miki T

14:08 73 NON-NEURONAL ACETYLCHOLINE AND ATP RELEASES FROM ISOLATED NORMAL AND NEUROGENIC

HUMAN BLADDER Yoshida M, Inadome A, Masunaga K, Sugiyama Y, Otani M, Iwashita H, Miyamae K, Ueda S

14:16 74 ESTROGEN SIGNIFICANTLY INFLUENCES DETRUSOR CONTRACTILITY IN FEMALE RATS

Hosoi T, Yokota T, Turuya Y, Matuoka T, Yamaguchi O 14:24 75 DIFFERENTIAL EXPRESSION OF EPITHELIAL SODIUM CHANNELS IN THE HUMAN AND RAT URINARY

BLADDER EPITHELIUM WITH AND WITHOUT OUTLET OBSTRUCTION. Du S, Araki I, Mikami Y, Kamiyama M, Beppu M, Takeda M

14:32 76 LONG TERM INVESTIGATION OF MICTURITIONAL PATTERNS AND TISSUE CONTENT OF NERVE

GROWTH FACTOR IN THE URINARY BLADDER OF STREPTOZOTOCIN-INDUCED DIABETIC RATS Sato K, Takimoto Y, Igarasi T, Sugimoto S, Kodama M, Wada Y, Kokubun S, Yosida T

14:40 77 IS ALPHA-1D ADRENERGIC RECEPTOR RESPONSIBLE FOR STORAGE SYMPTOMS IN MICE? : EFFECTS

OF ACETIC ACID ON BLADDER FUNCTION IN MICE LACKING ALPHA-1D ADRENERGIC RECEPTOR. Nakamura Y, Tsujimoto G , Tanoue A , Ikegaki I , Shinozaki S , Nimura T , Matsuda Y , Kawatani M

14:48 78 THE EFFECT OF MEMANTINE ON DETRUSOR OVERACTIVITY IN RATS

WITH SPINAL CORD INJURY Ozkurkcugil C, Komur O , Gokalp A

14:56 79 A LOW CONCENTRATION OF THE FLAVONOID AVOIDS THE PROGRESSIVE DECREASE OF BLADDER

SMOOTH MUSCLE CONTRACTILITY INDUCED BY REPETITIVE FIELD STIMULATION. Dambros M, van Koeveringe G, de Jongh R, Bast A, van Kerrebroeck P

15:04 80 ALPHA-1 ANTAGONISTS INHIBIT THE PRIMARY AFFERENT ACTIVITY FROM THE IRRITATIVE BLADDER

OF THE RAT. ISHIHAMA H, KAWATANI M, IKEDA M, MOMOTA Y

15:12 81 SPINAL CORD PHOSPHORYLATION OF EXTRACELLULAR SIGNAL-REGULATED KINASES (ERKS) IS

INDUCED BY SENSORY INPUT CONVEYED IN CAPSAICIN-RESISTANT BLADDER AFFERENTS AND CONTRIBUTES TO PAIN AND BLADDER REFLEX OVERACTIVITY IN A CHRONIC CYSTITIS RAT MODEL Cruz F, Cruz C , Charrua A, Avelino A , McMahon S B

15:20 82 MICTURITION INHIBITORY MECHANISM OF THE ROSTRAL PONTINE RETICULAR FORMATION AND THE

SPINAL GLYCINERGIC NEURONS IN RATS WITH OR WITHOUT CEREBRAL INFARCTION Nishijima S, Sugaya K, Miyazato M, Chinen Y, Morozumi M, Ogawa Y


Session 10 (cont) 15:28 83 THE ROLE OF DOPAMINE RECEPTORS ON LOWER URINARY TRACT FUNCTION IN PARKINSON’S

DISEASE PATIENTS Finazzi Agro E, Brusa L, Petta F, Miano R, Zuccalà A, D'Amico A, Stanzione P

15:36 84 THE PONTINE MICTURITION CENTRE IN THE PIG

Dalmose A L, Bjarkam C R, Djurhuus J C 15:44 85 EFFECTS OF L-DOPA ON URODYNAMIC FINDINGS IN PARKINSON’S DISEASE PATIENTS: ACUTE VS.

CHRONIC ADMINISTRATION Finazzi Agro E, Petta F, Brusa L, Miano R, D'Amico A, Parisi I, Stanzione P

15:52 86 AN ANATOMICAL STUDY OF THE OBTURATOR CANAL AND DORSAL NERVE OF THE CLITORIS AND

THEIR RELATIONSHIP TO TRANSOBTURATOR SLINGS Achtari C, McKenzie B, Briggs C, Rosamilia A, Dwyer P

14:00 - 15:30 Session 11 Poster - Help Seeking Behaviour - Maillot Room 14:00 87 PATIENT SELECTED GOALS: PERSPECTIVES ON SURGICAL OUTCOMES ONE YEAR AFTER SURGERY

Mahajan S , Elkadry E, Kenton K, Shott S , Brubaker L 14:07 88 MEASURING PATIENT EXPECTATIONS FOR INCONTINENCE CARE SEEKING

Heit M, Blackwell L , Kelly S 14:15 89 MEASURING BARRIERS TO INCONTINENCE CARE SEEKING

Heit M, Blackwell L , Kelly S 14:22 90 ARE INCONTINENT WOMEN FINDING THE HELP THEY SEEK?

Botros S, Gandhi S, Abramov Y, Nickolov A, Sand P, Goldberg R 14:30 91 DIFFERENCES IN PATTERNS OF LOWER URINARY TRACT SYMPTOMS AND HELP SEEKING

BEHAVIOUR BETWEEN MEN OF WHITE AND ASIAN ETHNIC ORIGIN. Taylor J, Harrison S, McGrother C, Assassa P

14:37 92 ANXIETY IN SPECIALIST CLINICS

Parsons M, Williams M , Cardozo L , Bidmead J, Hoey M , Thomas M , Robinson D , Balmforth J, Dixon A, Anders K

14:45 93 A SYSTEMATIC REVIEW OF THE PREVALENCE OF NOCTURNAL ENURESIS IN CHILDREN AND YOUNG

PEOPLE AGED 5-18 YEARS AND THE SOCIAL IMPACT ON THE INDIVIDUAL AND THEIR FAMILY Morison M, Staines H, Gordon A

14:52 94 CONSTRUCT VALIDITY OF THE INCONTINENCE SEVERITY INDEX

Murphy M, Culligan P, Arce C, Graham C, Blackwell L, Heit M 15:00 95 VALIDATION OF AN OAB SCREENER IN A PRIMARY CARE PATIENT POPULATION IN THE US

Coyne K, Margolis M, Zyczynski T, Elinoff V, Roberts R G 15:07 96 THE CORRELATION BETWEEN THE UROGENITAL DISTRESS INVENTORY/INCONTINENCE IMPACT

QUESTIONNAIRE AND OBJECTIVE MEASUREMENTS FROM THE BLADDER DIARY. van der Vaart H, van Brummen P, Heintz P

15:15 97 MENTAL HEALTH SCREENING IN FISTULA WOMEN IN A DEVELOPING COUNTRY

Goh J, Krause H, Sloane K, Akhter S 15:22 98 PREVALENCE OF BOWEL DISORDERS AND PELVIC ORGAN PROLAPSE COMPLAINTS IN RELATION TO

URINARY INCONTINENCE IN A GENERAL FEMALE POPULATION. Slieker-ten Hove M C P, Vierhout M, Bloembergen H, Schoenmaker G

14:00 - 16:15 Session 12 Podium - Paediatric Forum - 252b 14:00 99 ACCURACY OF BLADDER VOLUME DETERMINATION BY BLADDERSCAN IN PEDIATRIC AGE

De Gennaro M, Di Ciommo V, Capitanucci M L, Mosiello G, Orazi C , Schingo P, Adorisio O, Tubaro A 14:15 100 A RANDOMISED CROSSOVER STUDY OF DISPOSABLE PADS FOR INCONTINENT CHILDREN

Macaulay M, Pettersson L, Fader M, Brooks R, Cottenden A


Session 12 (cont) 14:30 101 TREATMENT OF VESICAL SPHINCTER DYSSYNERGIA IN CHILDREN USING EMG-BIOFEEDBACK –

RESULTS OF A 2 YEAR FOLLOW-UP STUDY Kracochansky M, Koch V, Schneider E , Arap S, Trigo Rocha F

14:45 102 VIDEOURODYNAMIC ASSESSMENT FOR DAYTIME URINARY INCONTINENCE ATTRIBUTABLE TO

OVERACTIVE BLADDER IN CHILDREN Kajiwara M, Inoue K, Kato M, Kurihara M, Usui A, Usui T

15:00 103 NERVE SPARING BILATERAL EXTRAVESICAL DETRUSORRHAPHY

Kim K M, Lee S W 15:15 104 IS NECESSARY ANTI-REFLUX SURGERY AT THE TIME OF AUGMENTATION CYSTOPLASTY FOR

CHILDREN WITH NEUROGENIC BLADDER AND HIGH GRADE VESICOURETERAL REFLUX? tanaka H , kakizaki H, moriya K, furuno T, nonomura K

15:30 105 LONG-TERM RESULTS AND RELAPSE RATES IN CHILDREN SUFFERING FROM MONOSYMPTOMATIC

NOCTURNAL ENURESIS AND OVERACTIVE BLADDER Marschall-Kehrel A, Mürtz G , Kramer G, Jünemann K P, Hjalmas K

15:45 106 WHAT HAPPENS WHEN CHILDREN TREATED WITH CAPACITY TRAINING FOR REFRACTORY

BEDWETTING GROW INTO ADULTHOOD Vermandel A, Wyndaele J

16:00 107 VESICAL AND BOWEL MANAGEMENT AND QUALITY OF LIFE IN SPINA BIFIDA ADULT PATIENTS:

RESULTS OF A MULTICENTER ITALIAN SURVEY De Gennaro M, Buffa P , Capitanucci M L, Battaglino G F, Beseghi U , Di Lorenzo F

Friday 27th August 2004 09:15 - 11:00 Session 13 Plenary Podium - Therapeutic Options, Experimental and Clinical - Main Auditorium 09:15 108 ADIPOSED DERIVED STEM CELLS SEEDED ON THE COLLAGEN MATRIX A NEW EXCITING OPTION FOR

TISSUE ENGINEERING RECONSTRUCTION OF THE LOWER URINARY TRACT. Almeida F G, Schor N, Leite K, Srougi M, Bruschini H

09:30 109 INHIBITION OF MITOCHONDRIAL NITRIC OXIDE SYNTHASE DURING PELVIC IRRADIATION PREVENTS UROTHELIAL DAMAGE AND PROTECTS THE BLADDER AGAINST RADIATION CYSTITIS Hayashi Y, Birder L, de Groat W, Epperly M, Peterson J, Greenberger J, Meyers S, Zeidel M, Kanai A

09:45 110 OBSTETRIC ANAL SPHINCTER INJURY (OASI) REPAIR- A PROTOCOL WITH A DIFFERENCE?

Thakar R, Andrews V, Sultan A 10:00 111 RAISING THE TONE: A PROSPECTIVE OBSERVATIONAL STUDY EVALUATING THE EFFECT OF PELVIC

FLOOR MUSCLE TRAINING ON BLADDER NECK MOBILITY AND ASSOCIATED IMPROVEMENT IN STRESS URINARY INCONTINENCE Balmforth J , Bidmead J , Cardozo L, Hextall A, Kelvin B, Mantle J

10:15 112 IMMEDIATELY OUTCOME OF DDAVP VERSUS BEHAVIOURAL MODIFICATION FOR TREATMENT OF

MONOSYMPTOMATIC NOCTURNAL ENURESIS: A PROSPECTIVE RANDOMIZED STUDY OF 30 PATIENTS Féra P, Glashan R, Lelis M A, Gonzales S R, Nogueira M D P, Almeida F, Srougi M, Bruschini H

10:30 113 A META-ANALYSIS OF THE INTRA-OPERATIVE SAFETY AND EFFECTIVENESS OF THE

TRANSOBTURATOR HAMMOCK SEEN IN RESULTS OF TWO PROSPECTIVE STUDIES IN 9 COUNTRIES WITH 204 PATIENTS Mellier G, Moore R, Jacquetin B

10:45 114 A RANDOMIZED CONTROLLED TRIAL OF FASCIA LATA FOR THE PREVENTION OF RECURRENT

ANTERIOR VAGINAL WALL PROLAPSE Gandhi S, Kwon C, Goldberg R P, Abramov Y, Beaumont J L, Koduri S, Sand P K

14:00 - 15:30 Session 14 Poster - Epidemiology and Outcomes Research - Maillot Room 14:00 115 DOES A HISTORY OF CHILDHOOD URINARY SYMPTOMS PREDICT ADULT SYMPTOMS?

Fitzgerald M P, Brown J S, Wassel Fyr C, Brubaker L, Thom D, Van Den Eeden S K, Subak L L, for the RRISK study group

14:07 116 THE NATURAL HISTORY OF URINARY STORAGE DISORDER IN OLDER WOMEN IN THE COMMUNITY; A

THREE YEAR PROSPECTIVE COHORT STUDY Donaldson M, McGrother C , Thompson J , Matthews R, Dallosso H


Session 14 (cont) 14:15 117 THE ASSOCIATION BETWEEN THE AGE AT THE FIRST AND LAST DELIVERY AND URINARY

INCONTINENCE Rortveit G, Hunskaar S

14:22 118 OBSTETRICAL HISTORY AND FAECAL INCONTINENCE. A CROSS-SECTIONAL STUDY AMONG 2640

WOMEN AGED FROM 49 TO 61 YEARS Fritel X, Ringa V, Saadoun K, Varnoux N, Piault S, Bréart G

14:30 119 THE ASSOCIATION BETWEEN CHRONIC RESPIRATORY SYMPTOMS AND URINARY INCONTINENCE IN

WOMEN Hannestad Y S, Hunskaar S

14:37 120 QUALITY INDICATORS AND STANDARDS OF CONTINENCE CARE FOR OLDER PEOPLE IN ENGLAND

Wagg A, Mian S, Potter J 14:45 121 THE MINIMUM CLINICALLY IMPORTANT DIFFERENCE IN INCONTINENCE QUALITY OF LIFE

QUESTIONNAIRE (I-QOL) TOTAL AND SUBSCALE SCORES IN WOMEN WITH STRESS URINARY INCONTINENCE (SUI) Yalcin I, Patrick D, Summers K , Kinchen K, Bump R

14:52 122 THE 24 HOUR PAD TEST: PAD COMPOSITION AFFECTS ACCURACY

Karantanis E, Miller T, Moore K 15:00 123 ARE URODYNAMIC INVESTIGATIONS A GOOD PROGNOSTIC TOOL FOR THE OUTCOME OF TVT?

Schraffordt S, Bisseling T, Heintz P, Vervest H 15:07 124 PELVIC FLOOR MUSCLE TRAINING ARE EFFECTIVE IN WOMEN WITH URINARY INCONTINENCE AFTER

STROKE Tibaek S, Gard G, Jensen R

15:15 125 A CROSS-OVER STUDY FOR EVALUATION OF FUNCTIONAL CONTINUOUS MAGNETIC STIMULATION

(FCMS) IN PATIENTS WITH URINARY INCONTINENCE ON PELVIC FLOOR MUSCLE EXERCISE (PFME) Suzuki T, Yasuda K, Yamanishi T, Kitahara S, Nakai H, Yamashita T, Sato R, Suda S, Ohkawa H

15:22 126 ADHERENCE TO THE ICS STANDARDISATION OF TERMINOLOGY OF LOWER URINARY TRACT

FUNCTION IN THE ABSTRACTS OF THE 2003 ANNUAL MEETING OF THE INTERNATIONAL CONTINENCE SOCIETY Pesce F, Rubilotta E, D'Amico A, Curti P P, Ballario R, Novara G, Artibani W

14:00 - 15:30 Session 15 Poster - Imaging & Urodynamics - 252a/b 14:00 127 BIOMETRY OF THE PUBORECTALIS MUSCLE AND HIATUS BY 3D PELVIC FLOOR ULTRASOUND

Shek K , Dietz H 14:07 128 URETHRAL SPHINCTER VOLUME MEASURED WITH MRI.

Tahara H, Okadome A, Tahaka M 14:15 129 COMPARISON OF ANATOMICAL AND CLINICAL RESULTS OF THE TRANSOBURATOR TAPE TECHNIQUE

(TOT) USING ULTRASOUND Pajoncini C, Natale F , Weir J, Cervigni M

14:22 130 CAN FREQUENCY-VOLUME CHART PREDICT BLADDER OUTLET OBSTRUCTION IN RATS

Suzuki K, Yoshimura Y , Yamaguchi O 14:30 131 ELECTROPHYSIOLOGICAL STUDIES OF THE FEMALE PELVIC FLOOR IN STRESS URINARY

INCONTINENCE: IS THE INTENSITY OF INCONTINENCE RELATED TO LOCAL NEUROLOGICAL DAMAGE? Cavalcanti G, Bruschini H, Manzano G, Giuliano L , Catarin M, Nunes K, Srougi M, Nóbrega J A

14:37 132 A METHOD FOR ANALYSIS OF PUDENDAL NERVE INTEGRITY THROUGH PENILE DORSAL NERVE

STIMULATION AND INTRAURETHRAL SURFACE ELECTRODE REGISTRATION. Catarin M, Manzano G, Bruschini H, Cavalcanti G, Juliano L, Nunes K, Arruda H, Srougi M, Nobrega J

14:45 133 ASSESSMENT OF URETHRAL FUNCTION USING URETHRAL RETRO-RESISTANCE PRESSURE IN

WOMEN WITH AND WITHOUT STRESS URINARY INCONTINENCE Slack M, Tracey M, Hunsicker K, Patel B, Godwin A

14:52 134 COMPARISON OF MEASUREMENTS OBTAINED WITH MICROTIP AND EXTERNAL WATER PRESSURE

TRANSDUCERS Visco A


Session 15 (cont) 15:00 135 THE INFLUENCE OF URODYNAMIC CATHETER ON IDIOPATHIC DETRUSOR-SPHINCTER DYSSYNERGIA

(DYSFUNCTIONAL VOIDING) DIAGNOSIS IN WOMEN Kalivas K, Dimitriadis G , Vasilakakis G, Katsikas V, Zougas K, Radopoulos D

15:07 136 BLADDER VOLUME SENSITIVITY OF NON-INVASIVELY OR INVASIVELY MEASURED ISOVOLUMETRIC

INTRAVESICAL PRESSURE van Mastrigt R, Huang Foen Chung J

15:15 137 THE USE OF A MODELIZED ANALYSIS OF FREE UROFLOWS (FF) TO IMPROVE WATCHFUL WAITING OF

PATIENTS WITH BENIGN PROSTATIC ENLARGEMENT (BPE). Valentini F, Hermieu J, Zimmern P, Nelson P , Besson G

15:22 138 ANALYSIS OF THE COUGH STRESS TEST AND MULTICHANNEL URODYNAMICS FOR THE DIAGNOSIS

OF STRESS URINARY INCONTINENCE IN WOMEN Lovatsis D, Drutz H, Petropoulos S

14:00 - 15:40 Session 16 Poster - Clinical Pharmacology and Overactivity - Blue Room 14:00 139 DOES THE BLADDER CONTRACTILITY CHANGE WITH ANTICHOLINERGIC THERAPY IN WOMEN WITH

DETRUSOR OVERACTIVITY? Hirani K, Rahmanou P, Lamba A, Dostonova A, Chaliha C, Khullar V

14:07 140 THE INFLUENCE OF ANTICHOLINERGICS USED IN INCONTINENCE TREATMENT ON SLEEP IN HEALTHY

VOLUNTEERS AGED 50 YEARS AND OLDER Diefenbach K, Arold G, Wollny A, Schwantes U, Haselmann J, Roots I

14:15 141 SOLIFENACIN STATISTICALLY SIGNIFICANTLY INCREASED CONTINENCE RATES IN SUBJECTS WITH

SYMPTOMS OF THE OVERACTIVE BLADDER SYNDROME Cardozo L, Robinson D, Drogendijk T, for the Solifenacin Study Group

14:23 142 FESOTERODINE A NEW EFFECTIVE AND WELL-TOLERATED ANTIMUSCARINIC FOR THE TREATMENT

OF URGENCY-FREQUENCY SYNDROME: RESULTS OF A PHASE 2 CONTROLLED STUDY. Chapple C

14:30 143 PROPIVERINE HYDROCHLORIDE IMMEDIATE (IR) AND EXTENDED RELEASE (ER):

COMPARISON OF EFFICACY AND TOLERABILITY IN PATIENTS WITH OVERACTIVE BLADDER Juenemann K, Hessdoerfer E, Unamba-Oparah I, Berse M, Bruenjes R, Madersbacher H, Gramatté T

14:38 144 A MULTICENTER,RANDOMIZED, PLACEBO-CONTROLLED TRIAL OF TROSPIUM CHLORIDE IN

OVERACTIVE BLADDER PATIENTS Rudy D, Cline K, Goldberg K, Harris R

14:46 145 DARIFENACIN, A MUSCARINIC RECEPTOR ANTAGONIST WITH SELECTIVITY FOR M3 RECEPTORS,

REDUCES INCONTINENCE AND NOCTURIA IN PATIENTS WITH OVERACTIVE BLADDER Hill S, Khullar V

14:53 146 COST-EFFECTIVENESS OF DESMOPRESSIN TABLETS (MINIRIN®) AS ADJUNCTIVE THERAPY TO

BEHAVIOURAL CHANGES IN THE TREATMENT OF NOCTURIA IN NORWAY Mattiasson A , Lundegaard Christensen T, Poulsen P B, Tangen T

15:01 147 INTRAVESICAL RESINIFERATOXIN FOR THE TREATMENT OF IDIOPATHIC DETRUSOR OVERACTIVITY

IN WOMEN: A RANDOMIZED DOUBLE-BLIND PLACEBO CONTROLLED STUDY Rios L, Mattos Jr D , Panhoca R , Srougi M , Bruschini H

15:09 148 PHASE TWO SAFETY AND EFFICACY STUDY OF SINGLE DOSE INTRAVESICAL RESINIFERATOXIN IN

PATIENTS WITH INTERSTITIAL CYSTITIS Payne C, Mosbaugh P, Forrest J, Evans R, Frumkin L

15:17 149 THE EFFECT OF CANNABINOIDS ON LOWER URINARY TRACT SYMPTOMS IN MULTIPLE SCLEROSIS: A

RANDOMISED PLACEBO CONTROLLED TRIAL (CAMS-LUTS STUDY) Freeman R , Adekanmi O, Waterfield M, Waterfield A, Bishop R, Zajicek J

15:24 150 A POSSIBLE EXPLANATION FOR THE EXCEPTIONAL EFFICACY OF BOTULINUM TOXIN TREATMENT

FOR DETRUSOR OVERACTIVITY Apostolidis A, Popat R, Yiangou Y , Dasgupta P, Anand P, Fowler C J

15:32 151 BOTULINUM TOXIN A (BOTOX®) IN NEUROGENIC URINARY INCONTINENCE: RESULTS FROM A MULTI-

CENTRE RANDOMISED, CONTROLLED TRIAL Schurch B, de Sèze M, Denys P, Chartier-Kastler E, Ismael S, Haab F, Everaert K, Keppenne V, Plante P, Perrouin-Verbe B, Kumar C, Fraczek S


1 Avery K1, Abrams P1, Chadwick M1, Donovan J2

1. Bristol Urological Institute, 2. University of Bristol DEVELOPMENT AND PSYCHOMETRIC EVALUATION OF THE ICIQ URINARY AND BOWEL INCONTINENCE MODULES: THE ICIQ-UI AND ICIQ-BI Hypothesis / aims of study The modular International Consultation on Incontinence Questionnaire (ICIQ) is being developed to produce a comprehensive and universally-applicable questionnaire for the assessment of a variety of pelvic symptoms, including those of the lower urinary tract, lower bowel and vagina, in clinical practice and research. Under the aegis of the ICI, new modules to assess urinary and bowel incontinence, the ICIQ-UI and ICIQ-BI, have been developed and evaluated. Urinary incontinence is the complaint of any involuntary leakage of urine (1). Bowel (anal) incontinence is “the involuntary loss of flatus, liquid or solid stool that is a social or hygienic problem” (2). These conditions are observed among adults of all ages and are known to be bothersome, with the ability to impair an individual’s quality of life (QoL) (2). The modules are intended to be universal, applicable to a wide range of individuals, including adult men and women of all ages (>18 years) in both the developed and developing world. Study design, materials and methods Studies of mixed design were undertaken to develop the modules and to examine their psychometric properties in accordance with standard methods of psychometric testing: (i) Content validity – 72 items for the ICIQ-UI and 76 items for the ICIQ-BI were determined following a combination of

systematic reviewing of previous questionnaires, expert consensus committee and interviews with 43 consecutive patients with urinary incontinence (29 females, 14 males, mean age 60.4 years, range 32 to 88) and 14 with bowel incontinence (7 males, 7 females, mean age 63.5 years, range 45 to 85), with the intention that the resulting questionnaires would provide comprehensive measures of the frequency, severity and impact on QoL of urinary and bowel incontinence in men and women. Levels of missing data were examined to assess the acceptability of items in a postal survey of a sample of adults attending urology and colorectal clinics with varying levels of urinary and bowel incontinence (ICIQ-UI total baseline sample: n=210: 184 females, 26 males, mean age 56.8 years, range 18 to 100; ICIQ-BI total baseline sample: n=48: 33 females, 15 males, mean age 50.8 years, range 22 to 80).

(ii) Construct validity – the ability of the modules to reflect theories underlying urinary and bowel incontinence was examined in groups of individuals from the total baseline samples. The ability of the ICIQ-UI to detect a difference in the prevalence of different types of urinary incontinence between males and females was investigated by Chi square (χ2) analyses. Univariable regression was used to determine if the ICIQ-UI could detect a difference in the level and impact on QoL of symptoms between individuals with different types of urinary incontinence and to determine if the ICIQ-BI could detect a difference in the level and impact of bowel incontinence between men and women. Simple additive scores were computed for the questionnaires to facilitate analyses (ICIQ-UI range 0-389, ICIQ-BI range 0-517; higher score indicates greater severity).

(iii) Convergent validity - the degree of association between comparable items in the ICIQ-BI and another measure of a related concept, the Wexner Continence Grading Scale – modified (WCGS-Kamm) (3) was investigated using Spearman’s rank correlation coefficient (rs). The association between ICIQ-BI and WCGS-Kamm scores was also investigated using Pearson’s product moment correlation coefficient (r).

(iv) Stability – the questionnaires were examined in a two week test-retest reliability analysis of 127 patients (111 females, 16 males, mean age 55.8 years, range 18 to 100) attending urology clinics and 27 patients (15 females, 12 males, mean age 55.6 years, range 33 to 80) attending colorectal clinics with varying levels of urinary and bowel incontinence. Agreement between test and retest responses to individual items and overall scores was examined by graphical analysis of paired differences and the weighted Kappa (ĸ) statistic.

(v) Internal consistency – the reliability of the questionnaires was further investigated by Cronbach’s coefficient alpha (α) using data provided by the total baseline samples.

Various sampling methods were employed to develop and evaluate the modules in samples who represented potential respondents, comprising adults of all ages, with or without different symptoms and levels of urinary and bowel incontinence. Significance was determined at the 5% level. Ethical approval was granted by the Local Research Ethics Committee. Results (i) Content validity - interviews and review by clinical and social science experts indicated that items were

well-interpreted and covered all important domains. The postal response rate was acceptable (ICIQ-UI: 51%; ICIQ-BI: 56%), with low missing data for most items (ICIQ-UI mean: 4.3%; ICIQ-BI mean: 4.6%).


(ii) Construct validity – the ICIQ-UI clearly distinguished between the types of urinary incontinence reported by males and females (χ2=27.7, P<0.001), with stress incontinence more common among women, in contrast to men who reported more urge incontinence. Mixed incontinence exceeded stress and urge incontinence in both sexes. There was also a statistically significant difference in the level and impact of symptoms between individuals with different types of urinary incontinence (P=0.0002), with greater severity among individuals with urge and mixed incontinence. The ICIQ-BI clearly differentiated between males and females (P=0.019), with significantly higher mean scores among women (mean 110.2, range 17 to 435) than men (mean 45.3, range 19 to 105).

(iii) Convergent validity – agreement between ICIQ-BI and WCGS-Kamm items ranged from moderate to strong (Spearman’s rs 0.48 to 0.89, P<0.0001 to P<0.01 for all). The ICIQ-BI score also correlated well with the WCGS-Kamm score (Pearson’s r 0.74, P<0.0001).

(iv) Stability – test-retest reliability was good overall for individual items. For items using three to six-point Likert response frames, the percentage of individuals reporting identical ratings or moving a maximum of one category between the time points (e.g. from ‘quite a bit’ to ‘moderately’) ranged from 64 to 100% (ICIQ-UI) and 89 to 100% (ICIQ-BI). 0 to 32% (ICIQ-UI) and 0 to 8% (ICIQ-BI) of individuals moved two categories or more. For items using wider 11-point visual analogue scales, 82 to 100% (ICIQ-UI) and 96 to 100% (ICIQ-BI) of individuals reported identical ratings or moved a maximum of three categories. Following further analyses, 66 of 72 ICIQ-UI items and 34 of 37 ICIQ-BI symptom items exhibited ‘good’ to ‘very good’ stability, with crude agreements of 74 to 100% and Kappa values of 0.61 to 1.00 for the ICIQ-UI (P<0.0001 to P<0.001 for 70 items, P>0.05 for two items) and crude agreements of 89 to 99% and Kappa values of 0.56 to 0.97 for the ICIQ-BI (P<0.0001 to P<0.001 for all). The remaining six ICIQ-UI items exhibited ‘fair’ to ‘moderate’ stability, with crude agreements of 74 to 90% and Kappa values of 0.20 to 0.60 (P<0.0001 for four items, P>0.05 for two items). The stability of the remaining three ICIQ-BI items was ‘moderate’, as indicated by crude agreements of 89 to 91% and Kappa values of 0.56 to 0.60 (P<0.001 for all). Agreements between test and retest scores for the ICIQ-UI and ICIQ-BI were ‘good’ (89%) and ‘very good’ (96%), with high Kappa values of 0.68 (P<0.0001) and 0.89 (P<0.0001), respectively.

(v) Internal consistency – Cronbach’s alpha coefficient was high for the total set of items in the ICIQ-UI (0.82 for males, 0.93 for females) and the ICIQ-BI (0.98). The Cronbach’s alpha statistics for ICIQ-UI domains assessing symptoms, male and female sexual matters and condition-specific QoL were 0.95, 0.82, 0.85 and 0.95, respectively, and for ICIQ-BI domains assessing symptoms and condition-specific QoL were 0.97 and 0.96.

Interpretation of results The ICIQ-UI and ICIQ-BI have been shown to be psychometrically robust, exhibiting good levels of reliability and validity. Consequently, users can be confident that the questionnaires reliably measure what is intended, and provide a legitimate and valid summary of the frequency, severity and impact on QoL of urinary and bowel incontinence. Whilst the high Cronbach’s alphas indicate that the questionnaires have excellent internal consistency, they also indicate some redundancy. The questionnaires are undergoing further evaluation, including item reduction, refinement of the scoring systems and international implementation. Concluding message The ICIQ-UI and ICIQ-BI supply the need for comprehensive, robust, universally-applicable, condition-specific questionnaires to assess the symptoms and impact of urinary and bowel incontinence. They will be of use in epidemiological and outcomes research and routine clinical practice, where a comprehensive summary of these conditions is required. References 1. 2002. The standardisation of terminology of lower urinary tract function: Report from the Standardisation sub-committee of the International Continence Society. Neurourol Urodyn 21(2):167-78. 2. Incontinence: Proceedings of the Second International Consultation on Incontinence, July 1-3, 2001. 2nd ed. Plymouth: Health Publication Ltd. 3. 1999. Prospective comparison of faecal incontinence grading systems. Gut 44(1):77-80. FUNDING: AstraZeneca Pharmaceuticals LP, Boehringer Ingelheim, Eli Lilly & Co, Ferring Pharmaceuticals, Novartis Pharma AG, Pfizer Ltd, Pharmacia Corporation, Yamanouchi Pharma America, Inc


2 Baessler K1, O'Neill S2, Maher C1, Battistutta D3

1. Royal Women's, Mater and Wesley Hospitals, 2. Royal Women's Hospital, 3. School of Public Health, QUT A VALIDATED FEMALE PELVIC FLOOR QUESTIONNAIRE FOR CLINICIANS AND RESEARCHERS Hypothesis / aims of study The aim of this study was to design and validate a pelvic floor questionnaire that assesses female bladder, bowel and sexual function, pelvic organ prolapse and condition-specific quality of life issues suitable for routine clinic and research. Study design, materials and methods The questionnaire was developed from several questionnaires and included additional clinically relevant questions. It was applied during an interview in an age-stratified random sample from the electoral roll of 493 women in the community aged 40-79 years. These women are taking part in a longitudinal study of ageing. Content validity was assessed by the level of missing data and ambiguous questions. Criterion validity was evaluated by comparing the questionnaire to previously validated and established instruments (1,2,3) and to clinical measurements like the ICS pelvic organ prolapse staging. To evaluate construct validity, the pelvic floor questionnaire was applied to a subgroup of 49 women (mean age 57±9 years) and compared with 25 age-matched women attending a urogynaecology clinic (mean age 58±15). Internal consistency was analysed using Cronbach’s alpha statistics. Reproducibility was evaluated in a re-test after 2-4 weeks in the subgroup of 49 women. A four-point scoring system was used for most items in the questionnaire apart from defaecation frequency, bowel consistency, sufficient lubrication, and the reason for sexual abstinence. Additive scores were calculated separately for bladder, bowel, pelvic organ prolapse and sexual symptoms domains. The scores were divided by the number of relevant questions and multiplied by 10 giving a value between 0 and 10 for each of the four domains and a maximum pelvic floor dysfunction score of 40. Results Content validity The questionnaire was easily applied to all women and there were no missing data. Questions regarding incontinence of flatus (from bowel questionnaire, 2) and prolapse sensation (from UDI, 1) were ambiguous and had to be rephrased. The prolapse questions however were easily understood by urogynaecological patients. Construct validity The questionnaire clearly distinguished the community and clinical populations. Bladder, bowel and prolapse symptom scores as well as individual responses differed significantly (Mann-WhitneyU and Chi-square tests, p<0.05). The sexual function score was not different between the populations but women in the community had a higher libido and frequency of coitus, and less dyspareunia than urogynaecological patients (Chi-square tests, p<0.05). Criterion validity The bladder function domain of the questionnaire was compared with the validated short version of the urogenital distress inventory (SUDI; 1). Resembling the construction of the SUDI, the two corresponding variables stress and urge incontinence were dichotomised and showed high agreement with the SUDI (Kappa 0.96 and 0.90; p<0.01). The SUDI score correlated significantly with the bladder function score in our questionnaire (Spearman’s rho 0.78). Bowel function correlated highly with corresponding items in the bowel questionnaire (2) (Spearman coefficients: faecal urgency 0.90, flatus incontinence 0.94, faecal incontinence 0.75, laxative use 0.95, straining 0.88, digitation 0.89, p<0.001). The sensation of prolapse and vaginal heaviness correlated weakly (Spearman correlations 0.16- 0.21) but significantly with the pelvic organ prolapse quantification (Aa,Ba,gh,Ap,Bp; p<0.001). Sexual function (n=257) was compared with the validated McCoy Female Sexuality Questionnaire (3) which uses a 7-point-Likert scale. Spearman’s correlation was high for the matching variable orgasm frequency (-0.78) and reasonable for dyspareunia (-0.62), enjoyment of sex (-0.55) and lubrication (-0.53). The McCoy sum score (excluding sexual fantasies, satisfaction of partner as lover and friend) correlated highly with the sexual function score (Spearman 0.95, p<0.001).


Reliability The Cronbach’s alpha for the four domains were: bladder function 0.80, bowel function 0.73, sexual function 0.63 and pelvic organ prolapse 0.62 for the community women and 0.93 for the urogynaecological patients. Test-retest reliability Between 78% and 100% of women answered the questions identically on both occasions and most of the remaining women answered within one category. Kappa values in the test-retest analyses varied between 0.4 and 1.0 with 81% of the items having Kappa values > 0.6. The bladder, bowel, prolapse and sexual symptom scores correlated highly between test and retest (Spearman’s rho 0.87, 0.90, 0.88, and 0.68, p<0.01; mean differences 0.10±0.7, 0.19±0.5, 0.04±0.2, and 0.04±0.7, respectively). Interpretation of results This questionnaire assesses all aspects of pelvic floor function including condition-specific quality of life issues in a reproducible and valid fashion. It is suitable for clinicians and researchers Concluding message Due to its easy application and clinical relevance, the questionnaire can be integrated in routine clinical assessment as an alternative to time-consuming self-administered separate bladder, bowel and sexual dysfunction questionnaires. References 1. Health-related quality of life measures for women with urinary incontinence: the Incontinence Impact Questionnaire and the Urogenital Distress Inventory. Qual Life Res 1994;3:291-306. 2. Bowel function and irritable bowel symptoms after hysterectomy and cholecystectomy – a population based study. Gut 1993;34:1108-1011. 3. The McCoy Female Sexuality Questionnaire. Qual Life Res 2000;9:739-745. 3 Abrams P1, Avery K1, Zyczynski T2, Kopp Z2, Coyne K3

1. Bristol Urological Institute, 2. Pfizer, Inc., 3. MEDTAP International, Inc. MEASURING PATIENT OUTCOMES IN OAB: THE OAB-Q, OAB-Q SF, OAB SCREENER AND ICIQ-OAB Hypothesis / aims of study Overactive bladder (OAB) is a symptom-based condition characterized by symptoms of urinary urgency, with or without urge incontinence, increased urinary frequency and nocturia (1). It is estimated that 10 to 20% of the population may have OAB (2). Therefore, a reliable and well-validated measure is needed to assess and track treatment outcomes. The OAB-q, which was derived from patient focus groups, is a symptom bother and health-related quality of life (HRQL) questionnaire (2). The OAB-q has been validated in over 2500 patients with good discrimination among patient subgroups and demonstrated responsiveness to treatment. However, the length of the OAB-q (33 items) may be burdensome to some patients, thus initiating a need for the development of a short form version. Additionally, many patients are not aware that OAB is a treatable condition and are not seeking care, revealing a need for a screening tool. The aim of this study is to review the development of the OAB-q and OAB-q short form (OAB-q SF) as well as the creation of the OAB screener. Study design, materials and methods The original OAB-q was developed from patient focus groups, clinician input and a review of the literature. It has performed extremely well in both population survey research as well as clinical research. The OAB-q consists of an 8-item symptom bother scale and 25 HRQL items that form four subscales (coping, concern, sleep, social interaction). For the development of an OAB-q SF and an OAB screener, retrospective analyses were performed on three different OAB patient samples: 1) two cross-sectional patient surveys (n=254 and 919); and 2) a 12-week clinical trial (n=865).


When developing the OAB screener, 4 draft screeners were created from the 33 OAB-q items. One screener was conceptually based (the Symptom Bother scale as a stand-alone screener), two were determined from Rasch analysis as differentiating normal from OAB, and the last was derived from recursive partitioning analysis differentiating normal from OAB patients. For the OAB-q SF, Rasch analysis was used to identify the most discriminating items with the OAB-q so that non-discriminating or repetitive items could be recommended for deletion. Once potential screener subscales and OAB-q SF items were identified, the following analyses were performed on all newly formed item subsets: item discrimination between “normal” and “OAB”, Cronbach’s alphas to assess the internal consistency of each subscale, t-tests and ANOVAs. Logistic regressions were used to examine the discriminative ability of the screener in determining “normal” versus “OAB” in the patient survey datasets. Effect sizes and change scores were calculated for the OAB-q SF in the clinical trial dataset to assess responsiveness. Results A series of iterative analyses were performed for both the screener and OAB-q SF. From the retrospective analyses, two potential screeners, the 8-item Symptom Bother scale and the 6-item recursive partitioning scale items, produced promising results and were moved forward to prospective validation. The 8-item screener performed well with little missing data (0.2%–0.6%) and high inter-item and item-to-total correlations (r = 0.42–0.86; p values < 0.001). The logistic regression models controlled for age and gender and the dependent variable was OAB diagnosis comparing No OAB versus Probable OAB. The c-index of this model was 0.96 with good model fit and a sensitivity and specificity of 98.0 and 82.7, respectively. For screener scores > 8 (range, 0–48), the odds ratio for having Probable OAB was 95.7 (95% CI: 29.3-312.0). For the OAB-q SF, the Symptom Bother scale was reduced to 6 items and the HRQL items were reduced to 13 items. When performing factor analysis on the 13 HRQL items, 3 subscales were formed: coping (5 items), sleep (3 items), and emotional/social (5 items). The OAB-q SF subscales were internally consistent with alphas ranging from 0.82 to 0.92 and effect sizes ranging from were 0.81 to 1.14. These ranges were comparable with the original OAB-q questionnaire version. Interpretation of results The OAB-q SF and OAB Screener, based on the OAB-q, are both reliable, valid and pertinent tools providing patient outcome assessments and screening for OAB. Utilizing retrospective data analysis is a cost-effective and time-saving way to examine potential uses of existing patient reported outcome measures, providing that the patients in the database are consistent with the target patient population and the goal of the new measure is conceptually consistent with the initial instrument. Concluding message For symptom-based conditions such as OAB, patient reported outcomes are the optimal treatment outcomes and relevant to disease screener development. To conserve resources and time, it is useful to adapt disease-specific questionnaires to meet current needs as long as conceptual congruency and patient consistency is present. The modular International Consultation on Incontinence Questionnaire (ICIQ) is currently being developed to produce a comprehensive and universally-applicable questionnaire for the assessment of a variety of pelvic symptoms, including those of the lower urinary tract, lower bowel and vagina, in clinical practice and research. Under the aegis of the ICI, a new module to assess both the symptoms and impact on QoL of OAB, the ICIQ-OAB, is being developed and evaluated. The OAB-q SF will be incorporated into the ICIQ-OAB module to assess the impact of this condition on patients’ lives. References 1. 2002. The standardisation of terminology of lower urinary tract function: report from the Standardisation Sub-

committee of the International Continence Society. Am J Obstet Gynecol 187(1):116-126. 2. 2002. Psychometric validation of an overactive bladder symptom and health-related quality of life questionnaire: the

OAB-q. Qual Life Res 11(6):563-574. FUNDING: Pfizer, Inc., Outcomes Research


4 Slieker-ten Hove M C P1, Vierhout M2, Bloembergen H3, Schoenmaker G4

1. Erasmus Medical Center, Department of Gynecology, 2. University Medical Center Nijmegen, 3. Erasmus Medical Center, Medical Faculty, 4. General Practitioners group Brielle, NL DISTRIBUTION OF PELVIC ORGAN PROLAPSE (POP) IN THE GENERAL POPULATION; PREVALENCE, SEVERITY, ETIOLOGY AND RELATION WITH THE FUNCTION OF THE PELVIC FLOOR MUSCLES. Hypothesis / aims of study The prevalence and distribution of pelvic organ prolapse in the general population is still largely unknown (1). This abstract reports on the prevalence and distribution of pelvic organ prolapse in the general female population aged 45-85 years. In addition the relationship of the POP was compared with the function of the pelvic floor muscles. This study was part of a large cross-sectional survey. Approval was given by the Medical Ethical committee. All data were analysed with SPSS version 10.1. Study design, materials and methods A community-based cross-sectional research based on a survey and an additional physical examination. The entire population of 2750 woman in a small town (age 45-85) was invited to fill in a questionnaire with different validated and invalidated questionnaires on urinary incontinence (UDI, IIQ, Euroquol)) and bowel disorders. A total of 1398 women consented (50%) In addition 653 out of the 1398 woman were randomly selected and invited to participate in a physical examination. There where no selection criteria for the population, besides age. All women underwent the pelvic organ prolapse quantification system examination (POP-Q) in dorsal lithotomy position during maximal Valsalva. The examination of the pelvic floor was based on the PERFECT assessment scheme and included a visual inspection of a pelvic floor contraction (inward movement), a counter action of the pelvic floor during coughing and the size of extra pelvic muscle activity. During palpation we looked at the voluntary contraction, relaxation and the reflex contraction during coughing. Stages of support were evaluated by variable for trends with Pearson’s χ2 statistics as well as for significant trend (2) Results A total of 653 woman were examined. The average age was 58 years, with a range of 45 to 85 years. Table 1 presents the POP-Q distribution. Table 2 presents the POP-Q stages in relation to the contractility of the pelvic floor muscles and in table 3 the coordination of the pelvic floor is shown in relation to the presence of POP. Variables in the survey with a statistically significant trend toward increased POP stage were advancing age, parity, history of hysterectomy or pelvic organ prolapse operations and postmenopausal status. Variables that were found insignificant were weight (mean BMI = 25.7), pulmonary disease, smoking (including number of cigarettes and years), history of hernia and hard physical work. Within the physical examination we looked at the overall function (force, endurance and co-ordination) of the pelvic floor musculature (PFM). The variables in these three groups, with a statistically significant trend toward increased POP stage, were better able to voluntary relax PFM, use of significantly more extra-pelvic muscles and (caudal) perineal descent when the woman is asked to contract the PFM. Variables with a statistically significant trend toward increased POP stage within the cough reflex were perineal descent, urine loss and increased presents of celes. 1. Percentages of subjects in each age group with various stages of pelvic organ support according to Pelvic organ prolapse quantification system (ICS) Age (y) Stage 0 Stage 1 Stage 2 Stage 3 Stage 4 45-50 n = 146 15.8 % 45.2 % 31.5 % 7.5 % - >50-55 n = 145 21.4 % 42.8 % 26.2 % 8.3 % 1.4 % >55-60 n = 137 29.9 % 32.1 % 29.2 % 8.8 % - >60-65 n = 77 20.8 % 37.7 % 26.0 % 15.6 % - >65-70 n = 63 30.2 % 27.0 % 34.9 % 3.2 % 4.8 % >70 n = 71 18.3 % 25.4 % 26.8 % 14.1 % 15.5 % Overall n = 639 (14 missing)

22.4 % 36.9 % 29.0 % 9.2 % 2.5 %


2. Percentages of subjects in pelvic floor muscle contractility with various stages of pelvic organ support according to Pelvic organ prolapse quantification system (ICS) PFM contractility Stage 0 Stage 1 Stage 2 Stage 3 Stage 4 Voluntary contraction Strong n = 294 20.1% 40.5% 26.2% 11.6% 1.7% Weak n = 180 22.8% 31.7% 34.4% 7.8% 3.3% Absent n = 139 23.0% 39.6% 28.8% 5.8% 2.9% Voluntary relaxation

Full n = 303 18.2% 39.9% 27.7% 11.6% 2.6% Partial n = 172 28.5% 29.7% 33.7% 5.2% 2.9% Absent n = 121 23.1% 43.0% 23.1% 9.1% 1.7% Extra pelvic muscle activity YES n = 221 16.3% 37.1% 34.4% 8.1% 4.1% NO n = 414 25.4% 37.0% 26.1% 9.9% 1.7% Perineal descent during contraction YES n = 566 19.6% 37.6% 30.6% 10.1% 2.1% NO n = 63 46.0% 31.7% 14.3% 3.2% 4.8%

3. Percentages of subjects in pelvic floor muscle coordination with various stages of pelvic organ support according to Pelvic organ prolapse quantification system (ICS) PFM coordination Stage 0 Stage 1 Stage 2 Stage 3 Stage 4 Cough reflex movement

Perineal descent NO n = 310 35.2% 29.4% 24.5% 9.0% 1.9% YES n = 329 10.3% 44.1% 33.1% 9.4% 3.0% Celes more present NO n = 464 30.8% 37.7% 23.5% 6.0% 1.9% YES n = 175 0.0% 34.9% 43.4% 17.7% 4.0% Urine loss NO n = 584 24.1% 36.8% 27.9% 8.7% 2.4% YES n = 55 3.6% 38.2% 40.0% 14.5% 3.6%

Interpretation of results The distribution of the POP-Q stages in the population is slightly different from an earlier study with less stage 0. Significant POP (stages 2, 3 and 4) was found in roughly 40%. There was a statistically significant trend toward increased POP-Q stage among women with many of the historically quoted etiologic factors for the development of pelvic organ prolapse. However traditional factors like frequent coughing, hard physical work and weight (BMI mean 26.2), were not significant related. Women with significant prolapse have poorer coordination, of the pelvic floor than women without prolapse. Concluding message Fourty per cent of the general female population aged 45-85 years has significant pelvic organ prolapse. The presence of POP is related to poor pelvic floor coordination, which is likely to be causative. References 1.The distribution of pelvic organ support in a population of female subjects seen for routine gynaecologic health care.Am J Obstet Gynecol. 2000 Aug;183(2):277-85 2.Factors associated with pelvic floor dysfunction with emphasis on urinary and faecal incontinence and genital prolapse: an epidemiological study. Fornell E.; Wingren G.; KjØlhede Acta Obstetricia et Gynecologica Scandinavica, April 2004, vol. 83, no. 4, pp. 383-389(7)


5 Morison M1, Staines H1, Sullivan F2, Wilson P3, Stone D3, Tappin D3, Henderson M1

1. University of Abertay Dundee, 2. University of Dundee, 3. University of Glasgow NATURAL HISTORY OF THE ACQUISITION OF NIGHT-TIME BLADDER CONTROL: TRACKING STUDY TO FOLLOW CHILDREN FROM AGE 3 1/2 YEARS LIVING IN SCOTLAND Hypothesis / aims of study 1. To gain more understanding of the natural history of the acquisition of night-time bladder control in pre-

school children and the prevalence of nocturnal enuresis. 2. To evaluate a number of factors that may affect the age at which children become reliably dry at night,

including: family history, parental concern, perceived control and optimism. 3. To explore the families’ perceptions of the economic burden of their child’s bed wetting. 4. To explore the appropriateness of the methods used by families for bedding protection. Study design, materials and methods Setting: Primary care, in Tayside and Greater Glasgow, Scotland. Sample: Parents of 500 children aged 39-42 months were recruited from 22 general practices from Tayside and Greater Glasgow, at the time of their child’s routine Community Child Health Surveillance check. A response rate of 99.8% was achieved. Design: A longitudinal survey. The research nurse explored with parents the child’s night time bladder control and any family history of bed wetting using a shortened form of the Family Perspectives on Bed Wetting Questionnaire(1). For those children still found to be wetting the bed the parents were further asked about: the severity of the bed wetting; the degree of their concern; the methods used for mattress protection; the burden on family finances; their perception of their own control over the situation and their optimism for the future. When the child was 4 years old the Research Nurse telephoned the family to ascertain whether the child was still wetting the bed. The parents of these children were invited to take part in a further structured interview. Results 38% of children aged 39-42 months were found to be wetting the bed at least once a week, with 31% wetting every night. 78% of those children reliably dry had been dry for more than 6 months and 38% for over a year. The prevalence of diurnal enuresis among children with nocturnal enuresis was 2%. The median age at which children became reliably dry in the day-time was 27 months. No statistically significant relationship was found between nocturnal enuresis and the number of siblings, the child’s birth order, the child’s birth weight, the Carstairs Deprivation Score(2) for the family address, the age when the natural mother was dry, the parents’ concern, perception of control, or optimism. However, an association was found between nocturnal enuresis and day-time wetting, which is congruent with other studies. 21% of parents of children aged 39-42 months were concerned about the bed wetting, rising to 38% of parents with children still wetting at age 4. Even at this young age, a third of parents had mixed feelings or were unhappy about the situation – long before most health care professionals perceive bed wetting to be problematic. Parents were most concerned about the effects on the child’s self esteem. When asked how much bother their child’s bed wetting was, in the practical sense, about 20% of parents had found it bothersome, and concerns included the extra laundry and other related practicalities. However, less than 20% of parents reported that their child’s nocturnal enuresis had placed more than a minimal financial burden on the family finances and 84 - 86% of parents stated that cost was not important when it came to deciding on how to manage the consequences of their child’s bed wetting. Most parents believed that effort and ability were important for their child to become dry at night. A competency framework relating to parents’ perceptions of their ability to help their child is presented. The model acknowledges the importance of parental expectations, as well as task difficulty, opportunity and the help required by both parents and children. Interpretation of results The management of nocturnal enuresis in pre-school children is left almost entirely to parents yet there has been little research into the size of the problem or parents’ beliefs or perceptions of their abilities to help their child to become dry at night. By the time the child is 39-42 months old many parents are concerned about the situation and pessimistic about their own ability to help. Furthermore, these parents did not see health care professionals as having an essential part to play in ensuring a successful outcome, and very few had


contacted a health care professional for advice about the practicalities. The parents of four year olds were increasingly concerned and some felt that health care professionals had little help to offer families with this problem. Concluding message In current practice, most active treatments, such as the use of the body-worn alarm, are not initiated until the child is at least 7 years old, despite evidence that successful treatment can be commenced earlier. This study has highlighted the need for family support and treatment protocols for the families of children aged 4-6 years, and a separate study is now underway to explore parents’ perceptions of their needs, prior to setting up and evaluating a service to supplement the clinics being run for older children. References

1. Parents’ and young people’s attitudes towards bedwetting (1998) British Journal of Urology 81: Supplement 3, 56-66.

2. Deprivation and Health in Scotland (1991) Aberdeen University Press, Aberdeen Scotland. FUNDING: Scottish Office: Health Department, Chief Scientist Office Primary Care Research Fund 6 Morris A R1, Mullan G2, Roscioli T2, Buckley M F2, Moore K H1

1. Pelvic Floor Unit, St George Hospital, Sydney, 2. Department of Haematology and Genetics, Prince of Wales Hospital, Sydney A GENETIC LINKAGE STUDY OF DETRUSOR OVERACTIVITY Hypothesis / aims of studyStudies of childhood nocturnal enuresis (NE) have hypothesised a genetic basis for the disease (linkage to chromosomes 4,8,12,13,22 has been observed). Amongst NE children who also daywet into adolescence, urodynamic tests reveal detrusor overactivity (DO) in most1. Adult patients with DO and a history of childhood daywetting have been shown to have a reduced response to treatment in the longterm2.This suggests that there may be a genetic predisposition for DO in some patients. Our aim was to test whether one of the NE genetic loci implicated in the genesis of childhood nocturnal enuresis may be identified amongst a large family in whom detrusor overactivity / overactive bladder syndrome (OAB) / day-wetting was common. Study design, materials and methods Local ethics approval was obtained. Determination of phenotype: A standardised history of ‘major’ and ‘minor’ OAB symptoms was taken. All adult participants were offered urodynamic assessment to confirm the prescence of DO. If urodynamics were declined then phenotype was established from a combination of clinical symptoms. These combinations were 2 minor + 2 major, 3 minor + 1 major or 3 major symptoms The scheme is analogous to that used to diagnose systemic lupus erythematosis (SLE). Amongst children, the presence of daywetting past age 5 was taken as evidence of DO. Table1 Symptoms used to define the DO phenotype in the absence of a cystometry test Minor symptoms Major symptomsFrequency > 8 voids/day Day wetting past age 5 Troublesome or regular urgency Urge incontinence

Urge incontinence provoked by audiovisual stimuli eg running water

Nocturia Bothersome leakage at orgasm Nocturnal enuresis Laboratory techniques: DNA was extracted from blood using standard methods. A partial genome was undertaken using markers at loci previously implicated in NE (D4S2960, D8S264, D12S80, D12S86, D13S263, D13S291, D22S343, D22S446). Preliminary logarithm of odds (LOD) score estimates were calculated manually assuming an autosomal dominant pattern of inheritance which is phase-known and with complete penetrance. A LOD score is a statistical measure of the likelihood that a locus contributes to the


aetiology of the disease being studied. Following preliminary results, a higher resolution scan was undertaken on chromosome 13 (figure 2) Results Figure 1. Pedigree of family (Affected members are in black, deceased are scored through)

A four generation family was identified. with members in Australia and the United Kingdom (Figure 1). Family members that were willing to be contacted by the investigators were invited to enrol in the study. Of these, 12 individuals agreed to participate comprising 10 (83%) adult females, 1 (8%) female child and 1 (8%) male adolescent. Urodynamics revealed DO in 2 of 12 (17%) (members II 5 & IV 18). A further 5 (42%) adult females declined testing but had the clinical phenotype of OAB, as did the child (persistent day-wetting). The remaining 4 (33%) were phenotypically normal.

Linkage analysis and LOD scores for loci previously associated with NE:The loci on chromosomes 4, 8, 12 and 22 did not segregate with the DO/OAB phenotype The locus D13S263 on chromosome 13 did segregate, with an approximate LOD score of 2.11 at a Recombination Fraction of 0.08. A high resolution scan was therefore undertaken (Figure 2)

Figure 2: Loci assessed in High Resolution Linkage analysis of proximal Chromosome 13

Locus Genetic distance from centromere (cM)

D13S1236 6.17 D13S175 9 D13S1243 11.21 D13S1304 15.7 D13S217 22.17 D13S289 27.29 D13S171 31.07 D13S219 35.5 D13S218 39.34 D13S263 43.2

Two alleles at D13S171 and D13S219 segregated with the phenotype, being present in all affected females and absent in most unaffected females. An exception occurred in IV12 who was phenotypically normal and therefore an obligate carrier. However, D13S263 which was previously implicated in NE by other groups lies distal to, and does not overlap with, the region defined in this study. It was only possible to calculate a LOD score for D13S171, as the allele frequency of D13S219 within the Caucasian population is not known. Table 2 Two point LOD scores for the microsatellite marker D13S171.

LOD SCORE AT � = MARKER LOCUS

cM

.0 .005 .01 .05 .1 .2 .4

D13S171 1.95 1.93 1.91 1.76 1.56 1.15 0.29

‘q’ arm

‘p’ arm

centromere


Interpretation of results The pedigree suggests an Autosomal Dominant mode of inheritance with decreased penetrance. None of the NE loci showed linkage in this family. Despite the modest LOD score for D13S171, lack of recombination between loci D13S171 and D13S219 suggests linkage in this family amongst members with DO/OAB. Concluding message To our knowledge this is the first investigation of a possible genetic aetiology in DO/OAB. We have observed a locus (D13S171) which is present in all subjects with DO/OAB phenotype. It is unrelated to the loci previously seen in NE. Knowledge of such a locus may affect prognosis and open up new avenues of research, such as alteration in detrusor receptor proteins. References 1Br Med J. 1(5954):364-7 2Neurourol Urodyn 2003;22(5):460-461 7 Farrell S1, Baskett T 1, Farrell K1

1. Dalhousie University THE CHOICE OF ELECTIVE CESAREAN DELIVERY IN OBSTETRICS: HOW DOES THE RISK OF PELVIC FLOOR INJURY INFLUENCE CLINICAL DECISION-MAKING? Hypothesis / aims of study There is a growing body of evidence in the medical literature implicating parturition with pelvic floor injury and its sequelae. There are those who believe that vaginal birth, particularly forceps assisted vaginal birth, is associated with significant injury to the pelvic floor - arguing that this injury is sufficient to warrant informed consent for vaginal delivery and the opportunity to choose elective cesarean. Alternatively, others believe that the evidence for the protective effects of cesarean delivery is inadequate and that the operative risks associated are significant. The purpose of this study was to survey health care professionals about their willingness to offer elective cesarean delivery and to evaluate how their knowledge of obstetric related pelvic floor injury influences their practice. Study design, materials and methods An author-compiled questionnaire was administered to health care professionals. The first part of the questionnaire addressed the issue of the effect of various modes of delivery on bladder and bowel continence. The questions were answered on a five-point Likert scale with a response format ranging from ‘never’ to ‘always’. Part two of the questionnaire presented various clinical scenarios to participants and asked them to indicate the mode of delivery they would recommend.In the first scenario six patients with different obstetrical histories request elective cesarean delivery. The participants were asked to indicate whether they would offer elective cesarean or a trial of vaginal birth for each of these patients. In the second scenario participants were asked to indicate how they would manage the same six women at a point in their labors where it was necessary to choose between a trial of forceps or cesarean delivery. . Possible confounding demographic factors which were considered in the analysis were: sex, age, basic medical training and subspecialty training, type of practice (private or academic), geographic location of practice, population size served by their obstetric hospital, number of deliveries performed per annum in their hospital and number of deliveries performed by the participant. Personal parity and modes of delivery were also examined. Chi square or Fischer’s exact tests were used to assess the effect of the demographic variables upon health professionals’ willingness to offer elective cesarean delivery. Correlations between beliefs in obstetrical risks for pelvic floor injury and willingness to offer elective cesarean were examined with Pearson’s correlation coefficients. Results One hundred and sixty-two questionnaires were completed. One hundred respondents were female (62%). Twenty-three percent (37/162) of respondents approved elective cesarean delivery after informed request in nulliparous women without an obstetrical indication. Males were more likely than females to perform cesarean


delivery in these circumstances (34% versus 16% - OR 2.7, CI 1.2, 6.0). When questioned about the impact of mode of delivery on bladder and bowel continence, the numbers of respondents who answered “usually” or “always has a detrimental effect ” were: vaginal birth - 16%; forceps - 20%; and cesarean delivery reduces bladder and bowel problems - 44%. Males were more likely to emphasize a protective effect of cesarean delivery (55% versus 38%; OR 1.9, CI 1.0, 4.0). Health care professionals would opt for cesarean delivery for themselves when forceps was the alternative more often than they would offer cesarean delivery to their patients (OR 1.98, CI 1.1, 3.5). There was a low correlation between the willingness to offer elective cesarean and the belief that vaginal birth ( r = 0.16) or forceps assisted vaginal birth ( r = 0.23) have detrimental effects on bowel and bladder continence. Interpretation of results We found the majority of respondents believed that both spontaneous vaginal birth and forceps delivery can have detrimental effects on bladder and bowel continence and that cesarean delivery has a protective effect. This finding indicates that there is a widespread recognition and acceptance of the body of literature implicating childbirth with pelvic floor injury. The low correlation between this recognition and a willingness to offer elective cesarean suggests that this knowledge does not influence obstetric practice. Concerns about the risks associated with cesarean delivery appear to overshadow concerns about the potential for pelvic floor injury associated with spontaneous or forceps assisted vaginal birth. Concluding message While the body of evidence implicating vaginal birth with urinary and anal incontinence is substantial, it is not consistent. Factors other than vaginal birth are clearly implicated in urinary and anal incontinence and this evidence causes clinicians to question the long-term protective effects of cesarean delivery. Perioperative complications associated with intrapartum cesarean delivery are much higher than those associated with elective cesarean. However, the implications of cesarean delivery for subsequent pregnancies (uterine rupture, placenta previa and placenta previa accreta) must also be considered. FUNDING: Atlee Foundation 8 Goldberg R1, Gandhi S1, Abramov Y1, Botros S1, Nickolov A1, Sherman W1, Sand P1

1. Evanston Continence Center, Northwestern University DELIVERY MODE IS THE MAJOR DETERMINANT OF STRESS URINARY INCONTINENCE IN PAROUS WOMEN: ANALYSIS OF 288 IDENTICAL TWINS Hypothesis / aims of study Identical twin studies are regarded as an ideal methodology for assessing the contribution of environment to human disease states, providing a degree of ‘natural control’ over genetic variance that cannot be achieved within random samples of unrelated individuals. We conducted an extensive survey of incontinence symptoms at the world’s largest annual gathering of twins, to determine the main environmental risk factors associated with stress urinary incontinence (SUI). Study design, materials and methods The 67-item survey of incontinence and pelvic floor symptoms was completed by 144 identical twin sister pairs (n=288) attending the 2003 Twins Days Festival. To account for correlated data within pairs, we implemented logistic regression models for repeated binary measures. A wide array of medical, obstetrical and demographic factors underwent univariate analysis and entered multivariate regression based on p<.25. Three models were utilized: (A) all pairs including those with nulliparous women (n=288), (B) pairs for which both sisters gave birth by either vaginal or cesarean delivery mode (n=196), and (C) pairs for which both sisters specifically had at least one prior vaginal birth (n=146). This facilitated evaluation of all demographic, environmental and obstetrical risk factors in the dataset while maintaining statistically valid reference groups. Univariate (t-test, chi2) and stepwise multivariate analyses were performed with Excel® and SAS®.


Results Demographics of the sample included mean age 47.5 (21-79), parity 1.8 (0-7), 45% menopausal, mean BMI 26.6, 90.3% Caucasian and 7.0% African American. Past surgeries included hysterectomy (20%) and SUI repair (2.4%). Stress incontinence was reported by 53.9% of the overall cohort; 91% had 1-5 weekly episodes, 9% had >5. Among 83.8% of parous women who had at least one vaginal birth, 65.5% reported SUI. Among 16.2% of parous women who delivered by ‘cesarean only’, 35.5% reported SUI. Regression Model A focused solely on non-obstetrical factors, confirming associations between SUI and age>40 (OR 4.6, p=0.001), menopause (OR 1.8, p=0.02), parity (OR 2.8 for 1 birth; OR 4.9 for >2 p=0.001) and BMI>30 (OR 2.8, p=0.002). The major study findings derive from Model B, designed to assess obstetrical risk factors in parous-parous twin pairs. This model revealed delivery mode as the strongest, and indeed, the only variable remaining independently predictive of SUI – with delivery by ‘cesarean only’ conferring a nearly 3-fold reduction in SUI risk relative to those having undergone vaginal birth (OR 0.36, p=0.013). Non-significant factors included parity, BMI, prolonged 2nd stage, newborn weight and hysterectomy. Finally, Model C evaluated factors specific to the vaginal birth mode. Despite a trend toward more SUI after forceps (OR 1.8, p=0.16), neither forceps nor episiotomy (OR 1.2, p=0.71) reached significance. Interpretation of results This represents the first application of an identical twin research design to female incontinence, providing nearly complete control over genetic risk factors (‘nature’) that may often confound the study of environmental risk factors (‘nurture’). Among all modifiable risk factors, delivery mode appears to be the most potent determinant of stress urinary incontinence in parous women. At all levels of parity, vaginal childbirth conferred a markedly higher risk of SUI (OR=2.78, p=0.013) than ‘cesarean only’ birth. Concluding message Delivery mode is the major environmental determinant of SUI, among younger childbearing women. These findings may provide new insight into the epidemiology of female incontinence, and highlight the impact of obstetrical choices on post-reproductive urinary function. 9 Abramov Y1, Sand P K1, Gandhi S1, Botros S1, Nickolov A2, Sherman W1, Goldberg R P1

1. Evanston Continence Center, Northwestern University, Feinberg School of Medicine, 2. Center on Outcomes, Research and Education, Evanston Northwestern Healthcare PREVALENCE AND RISK FACTORS FOR ANAL INCONTINENCE: NEW INSIGHT THROUGH AN IDENTICAL TWIN SISTERS STUDY Hypothesis / aims of study Anal incontinence (AI) is a symptom associated with a potentially devastating impact on physical and psychosocial health. The higher prevalence of AI in women as compared to men is primarily attributed to childbirth. Although several risk factors associated with mode of delivery as well as obstetric complications and interventions have been suggested, their relative importance is unknown, and their effect may be confounded by genetic risk factors (1). The current study is the first to use an identical twin model in order to allow for optimal assessment of environmental risk factors for AI by controlling for genetic variance. Study design, materials and methods An extensive survey of incontinence symptoms was conducted at the world’s largest annual gathering of twins at the 2003 Twins Day Festival, in Twinsburg, Ohio, U.S.A. 148 pairs of identical twin sisters completed questionnaires detailing the presence, frequency and severity of AI. We utilized a logistic regression model with repeated binary measures in order to account for correlated data within pairs (2). Univariate analysis as well as a multivariate stepwise logistic regression models were implemented to a large number of demographic, medical and obstetrical factors. In order to maintain statistically valid reference groups, we utilized 3 different models: The first, concentrated on non-obstetrical risk factors and included all pairs of twins (n=296); the second evaluated obstetrical risk factors in parous-parous twin pairs where both sisters delivered by either vaginal or cesarean section (CS) (n = 196), and the third was designed to evaluate factors specific to the vaginal birth mode and included pairs where both sisters had at least one previous vaginal delivery (n=146). We performed the univariate (t and Chi square tests), and stepwise multivariate analyses using Excel and SAS.


Results Table 1: Demographic data (n=296) Age (years) 49 ± 12 Parity 1.8 ± 0.3 BMI 27 ± 6.3 Race Caucasian 266 (90%) African American 21 (7%) Postmenopausal 133 (45%) Past surgeries Hysterectomy 59 (20%) Anti-incontinence surgery 7 (2.4%) Parous 228 (77%) Vaginal birth 194 (86%) Forceps 55 (24%) Episiotomy 164 (72%) CS only 31 (14%) Elective 4 (2%) During labor 27 (12%) Values are presented as means ± SD or as number (percent). Table 2: Prevalence of anal incontinence (%) Fecal Flatal Any All women 12 26 31 Parous 13 32 37 Vaginal births 17 34 40 CS only 6 31 36 Elective 0 0 0 During labor 8 37 41 Forceps delivery 9 26 29 Episiotomy 19 34 41 Table 3: Odds ratios of various risk factors for anal incontinence Variable Fecal P Flatal P Any P Age >40 1.84 0.035* 1.98 0.028* 2.07 0.024* Menopause 2.20 0.001* 2.50 0.004* 2.25 0.017* Parity 1 0.32 0.34 3.86 0.007* 3.15 0.011* ≥ 2 3.12 0.054 4.15 0.002* 3.69 0.001 Stress Urinary Incont. 3.3 0.027* 1.85 0.019* 1.82 0.019* CS only 0.62 0.42 0.68 0.33 0.74 0.43 Episiotomy 1.89 0.30 1.41 0.31 1.53 0.22 Prolonged 2nd stage 1.65 0.34 1.17 0.91 1.05 0.66 Forceps delivery 0.41 0.22 0.48 0.22 0.52 0.10 Birth weight > 4 Kg 0.68 0.52 0.67 0.25 0.55 0.10 Smoking 0.71 0.58 0.62 0.63 0.85 0.81 BMI>25 1.46 0.38 1.50 0.22 1.22 0.50 Prev. Hysterectomy 1.32 0.47 0.94 0.74 1.004 0.99


Interpretation of results Any type of AI (flatal or fecal) was reported in 31% of all women (Table 2). The prevalence of flatal incontinence was twice that of fecal incontinence (26% vs. 12%). Significant risk factors for AI included age >40, menopause, parity, and presence of stress urinary incontinence (Table 3). Among women who had CS only, those who had CS after initiation of labor had lower rates of fecal but similar rates of flatal incontinence than women who had vaginal delivery. Women who had planned (elective) CS reported no fecal or flatal incontinence (Table 2). Although not statistically significant, episiotomy and prolonged 2nd stage of labor were associated with increased risk for anal incontinence. Forceps delivery, high birth weight, previous hysterectomy, BMI and smoking habits did not affect the risk for AI. Concluding message This is the first study to apply an identical twin research design to female AI, providing almost absolute control over genetic risk factors. AI was reported by nearly one third of these community dwelling women, increasing with age, menopause and parity. While CS after initiation of labor conferred protection against fecal incontinence only, elective CS seemed to be protective against both fecal and flatal incontinence. Future studies should investigate the possible role of elective caesarean delivery in preventing AI. References 1. Does cesarean delivery prevent anal incontinence? Obstet Gynecol 2003; 101: 305-12. 2. Hardin JW, Hilbe JM. Generalized estimating equations. Chapman & Hall/CRC, Boca Raton, Florida, 2003. 10 Morkved S1, Salvesen K Å 21. Norwegian University of Science and Technology, 2. Department of Obstetrics and Gynecology, Trondheim University Hospital St. Olav, N-7006 Trondheim, N DOES PELVIC FLOOR MUSCLE TRAINING DURING PREGNANCY HAVE AN EFFECT ON LABOUR? Hypothesis / aims of study Intensive pelvic floor muscle training during pregnancy has been shown to prevent urinary incontinence (1, 2), and pregnant women are commonly encouraged to train their pelvic floor muscles. However, there is a myth that pelvic floor muscle training during pregnancy may cause prolonged labour. In theory, strong and voluminous pelvic floor muscles can obstruct labour. An opposite theoretical assumption is that training of the pelvic floor muscles may improve muscle strength and awareness and produce strong, flexible and well-controlled muscles that will facilitate labour. The primary aim of this randomised controlled trial was to assess if pelvic floor muscle training during pregnancy could prevent urinary incontinence. The results have been reported and published previously. This report deals with secondary outcomes of the trial, related to labour. The aim was to examine a possible effect of pelvic floor muscle training during pregnancy on labour. Study design, materials and methods A single-blind randomised controlled trial was conducted at one University hospital and three outpatient physiotherapy clinics in a primary care setting. The Regional Medical Ethics committee approved the trial. Nulliparous women attending a routine ultrasound scan at 18 weeks of pregnancy were invited to participate in the trial. In all 342 women gave signed consent to participate, 41 women were excluded or withdrew before the first examination leaving 301 healthy nulliparous women that were randomly allocated to a training group (148) or a control group (153). The training group followed a structured training program with pelvic floor muscle exercises between 20 and 36 weeks of pregnancy. Women in the training group trained with a physiotherapist in groups of 10-15 women for 60 minutes once per week for a period of 12 weeks. Group training was performed in lying, sitting, kneeling and standing positions with legs apart to emphasise specific strength training of the pelvic floor muscles and relaxation of other muscles. Body awareness, breathing and relaxation exercises and strength training for the abdominal, back and thigh muscles were performed to music between positions. In addition, the women were encouraged to perform 8-12 intensive pelvic floor muscle contractions twice per day at home. The control group received the customary information given by their midwife or general practitioner.


Main outcome measures were duration of the first and the second stage of labour (3), operative delivery for prolonged second stage, and episiotomy. Neonatal size, Apgar score and umbilical cord pH were also registered. Results There was no difference between groups in the duration of the first stage of labour (median values 260 min v 260 min, p = 0.57). The women in the training group had somewhat shorter duration of the second stage of labour (median values 35 min v 45 min), but the difference was not statistically significant (log rank test p=0.3). The neonates were slightly smaller, but there was no difference in Apgar score or umbilical cord pH. Interpretation of results Intensive pelvic floor muscle training during pregnancy does not cause prolonged labour. Concluding message Pelvic floor muscle training during pregnancy does not seem to effect labour negatively. The myth that pelvic floor muscle training during pregnancy will cause prolonged labour was not confirmed in this trial. References

1. Prevention of postpartum stress incontinence in primigravidae with increased bladder neck mobility: A randomised controlled trial of antenatal pelvic floor exercises. Br J Obstet Gynecol 2002;109:68-76.

2. Pelvic floor muscle training during pregnancy to prevent urinary incontinence: A single-blind randomized controlled trial. Obstet Gynecol 2003;101:313-19.

3. Williams obstetrics 20th edition. Appleton Lange, Connecticut 1997, p. 415-20. 11 Fernando R1, Sultan A2, Kettle C1, Radley S3, Jones P4, O'Brien S1

1. University Hospital of North Staffordshire, Stoke on Trent, 2. Mayday University Hospital, Croydon, Surrey, 3. Queen Elizabeth Hospital, Birmingham, 4. Keele University, Staffordshire A RANDOMISED TRIAL OF OVERLAP VS END-TO-END PRIMARY REPAIR OF THE ANAL SPHINCTER Hypothesis / aims of study Anal incontinence can have a devastating effect on a woman’s quality of life. Obstetric anal sphincter injury (OASI) is the major cause of anal incontinence. Despite primary end-to-end anal sphincter repair, up to 59% of women suffer anal incontinence and sonographic sphincter defects have been demonstrated in about 85% of women. In a non-randomised study using the overlap technique better results has been demonstrated1. We aimed to perform a randomised study to determine the outcome of primary repair of OASI comparing the end-to-end to overlap technique. Study design, materials and methods A prospective multicentre randomised controlled study was designed to compare overlap and end-to-end techniques for primary external sphincter repair of OASI. The primary outcome of the study was anal incontinence, which include faecal urgency, faecal urge incontinence, flatus incontinence, liquid and solid faecal incontinence at twelve months. The secondary outcomes were perineal pain, dyspareunia, quality of life, anal sphincter defects detected by endoanal scans and ano-rectal manometry at twelve months. To show any significant difference with adequate power, 24 patients were required in each arm of the study. Ethical approval was obtained from the local ethics committees of the participating centres. A total of 64 patients with OASI of 3b, 3c and 4th degrees were recruited for the study during a 24 month period from two hospitals. All repairs were carried out by two trained obstetricians and a specialist midwife according to an ethically approved study protocol. Patients were followed-up with questionnaires at 6 weeks, 3, 6 and 12 months and invited to have endoanal scans and anal manometry at 6 and 12 months. Specialists reporting endoanal scans and the technician performing anal manometry were blinded to the technique of repair.


Results The baseline characteristics were comparable in both groups. The mean duration of overlap repair was 39 minutes compared to 29 minutes for end-to-end repair (p=0.003). The mean blood loss associated with overlap repair was 259 ml compared to 203 ml in the end-to-end group (p=0.05). None required blood transfusion. Twenty percent of the patient in the end-to-end group complained of perineal pain whereas none of the patients in the overlap group complained of perineal pain at 12 months (p=0.04). Thirty two percent of the end-to-end group noted that faecal urgency & faecal urge incontinence symptoms either became worse or not improved over the 12 months whereas all the patients in the overlap group noted an improvement (p=0.01). There were no statistically significant differences between the two techniques in terms of dyspareunia, quality of life, anorectal manometry and endoanal scan findings. None of the patients from either group complained of suture migration. There were no statistically significant differences in the primary and secondary outcomes between the operators. A summary of primary outcome results is shown in Table 1.

Table 1: Primary outcome at 12 months Outcome Overlap (n=27) End-to-end (n=25) p value Overall anal incontinence 5 (18.5%) 10 (40%) 0.13 Faecal urgency 1 ( 3.7%) 8 (32%) 0.02 Faecal urge incontinence 0 6 (24%) 0.01 Flatus incontinence 4 (14.9%) 4 (16%) 1 Liquid faecal incontinence 0 1 ( 4%) 0.48 Solid faecal incontinence 0 0 -

Interpretation of results This is the first randomised controlled study to show a significant improvement in faecal urgency and faecal urge incontinence with primary overlap repair at twelve months. There was a 22% reduction of overall anal incontinence in the overlap group compared to end-to-end group although non significant. There is only one published randomised controlled study2 that reported no difference in outcome at 3 months follow-up. However they did not analyse the different components of anal incontinence separately (external sphincter injury is associated with urgency and urge incontinence) and did not exclude Type 3a OASI (partial tears), where an overlap repair is not possible without completely dividing the rest of the sphincter. In our study all repairs were carried out by only three experienced operators and this may have contributed to the better outcome in the overlap group. In addition the overlap group showed a rapid improvement of symptoms over one year. A possible explanation may be that with the overlap there is better apposition whereas with end-to-end repair there may be ischaemia of the muscle ends and possible scarring. The steady improvement of symptom severity with time highlights the necessity for longer term follow-up with OASI repair. This study also demonstrates that outcome of primary overlap repair is more favourable than secondary overlap repair3. Concluding message Primary overlap repair of OASI is a feasible technique and is associated with a lower prevalence of long-term anal incontinence. Use of this technique by trained operators can minimise the risk of anal incontinence following obstetric anal sphincter injury. References 1. Primary repair of the obstetric anal sphincter rupture using the overlap technique. Br J Obstet Gynaecol 1999;106:318-323 2. A randomised controlled trial comparing primary overlap with approximation repair of third degree obstetric tears. Am J Obstet Gynaecol 2000:183:1220-4. 3. Long term results of overlapping anterior anal sphincter repair for obstetric trauma. Lancet 2000;355:260-65. FUNDING: REMEDI, Bath, UK 12 Goh J1, Carey M1, Tjandra J2

1. Royal Women's Hospital, 2. Royal Melbourne Hospital DIRECT END-TO-END OR OVERLAPPING DELAYED ANAL SPHINCTER REPAIR FOR ANAL INCONTINENCE: LONG-TERM RESULTS OF A PROSPECTIVE RANDOMISED STUDY. Hypothesis / aims of study Anal incontinence is a distressing problem with a reported prevalence in the general population of 2.2% and up to 6.6% at 10 months postpartum (1). The widespread usage of anal endosonography has demonstrated


anterior defects of the external anal sphincter as a common cause of anal incontinence. The overlapping external anal sphincter repair procedure has been considered the “gold standard” procedure for anal incontinence secondary to external anal sphincter defects. However, a recent review indicated that the overlapping anal sphincter repair following obstetric trauma was also associated with residual symptoms and new evacuation disorders (2). Alternatives to an overlapping procedure include a direct end-to-end anal sphincter repair procedure. This approach is simpler to perform than an overlapping sphincter repair, requiring less tissue dissection. The aim of this study was to compare the results of two different surgical techniques, namely, direct end-to-end versus overlapping in delayed repair of a localised anterior external anal sphincter defect in women with anal incontinence. Study design, materials and methods Inclusion criteria included symptomatic anal incontinence, isolated anterior external anal sphincter defect, normal pudendal nerve terminal motor latency. During the 5-year period from 1998 to 2001, 36 women were assessed as potential subjects for the study. Thirteen were excluded from the study because of prolonged pudendal nerve terminal motor latency (n=9) or refusal to participate (n=4). The remaining 23 patients were randomised to either a direct end-to-end repair (n=12) or an overlapping sphincter repair (n=11). The median age of the women treated by end-to-end and by overlapping repair was 47 years (range 32-71) and 45 years (range 31-68) respectively. All women completed consent documents for voluntary participation in the study that had been previously approved by the institution review board Preoperative assessment included a detailed history and examination, endoanal ultrasonography, anorectal manometry and neurophysiological evaluation including pudendal nerve terminal motor latency (PNTML). Anal incontinence was assessed by the Cleveland Clinic continence score (0-20; 0 = perfect continence, 20 = complete incontinence). The median pre-operative continence score (Cleveland Clinic) was 17 in both the direct repair group (range 8-20) and the overlap group (range 7-20). Technique All women received full bowel preparation preoperatively and intraoperative prophylactic antibiotic therapy. Surgery was performed with patients in the prone position. A curvilinear perineal incision was made between the introitus and anus. Dissection was continued to adequately mobilize the external anal sphincter cephalad to the anorectal ring. Care was taken to preserve branches of the pudendal nerves by not extending the dissection posterolaterally. Direct or overlapping repair was performed using 2/0 PDS (Ethicon, Inc., Somerville NJ) sutures. With the overlapping repair, greater mobilization of the external anal sphincter was often required to avoid excessive tension on the repair. The perineal skin was closed with interrupted 3/0 Vicryl (Ethicon) sutures. The women were allowed to have a normal diet the following day. Neither stool softeners nor constipating agents were routinely used. Results Both groups were comparable with regard to age, past history of sphincter repair (n=2) and posterior vaginal repair. There was no major intra- or post-operative morbidity. The wound healing rate was identical for both groups. The median follow-up period was 26 months (range 18-38). At review the median continence score in both groups was 4 compared to a median pre-operative continence score of 17 in both groups. In both surgical groups, there was similar improvement in maximum squeeze pressure and in the functional anal canal length following surgery, but the median resting pressure remained relatively unchanged. In the group treated by anal sphincter overlap, 1 patient developed a unilaterally prolonged PNTML that persistent 26 months after surgery. Interpretation of results In this study, the outcomes in improved continence in the direct end-to-end external anal sphincter repair compared to the overlapping repair were similar at a median of 26-months follow up. The small number of women recruited over a 5-year period underscores the need to conduct future similar studies in multiple centres. Concluding message Both the direct end-to-end and overlapping delayed anal sphincter repair procedures for anal incontinence resulted in similar marked improvement in continence scores. The overlapping repair often required more


tissue dissection and may be associated with more difficulties in fecal evacuation when compared to the direct end-to-end repair procedure. Reference 1. Anal endosonography and its role in assessing the incontinent patient. Best Practice & Research Clinical Obstet &

Gynaecol 2004; 18: 157-73 2. Long-term results of overlapping anterior anal sphincter repair for obstetric trauma. Lancet 2000; 355: 260-5. 13 Al-Hayek S1, Thomas A1, Abrams P1

1. Bristol Urological Institute THE NATURAL HISTORY OF DETRUSOR CONTRACTILITY: MINIMUM 10-YEAR URODYNAMIC FOLLOW UP IN MEN WITH BLADDER OUTLET OBSTRUCTION AND THOSE WITH DETRUSOR UNDERACTIVITY Hypothesis / aims of study Detrusor function during voiding is classified by the International Continence Society (ICS 2002) into 3 categories: normal, underactive and acontractile. There is little in the literature as to what detrusor contractility change with time. This study aimed to assess the long-term effect, in male patients, of treated and untreated bladder outlet obstruction (BOO) on detrusor contractility and to explore the relationship between aging and detrusor underactivity (DUA). Study design, materials and methods Men investigated at our urodynamic department between 1972 and 1986 were traced and two groups were identified and invited for repeat pressure-flow urodynamic test. The first group included those aged over 40 with urodynamic diagnosis of bladder outlet obstruction at the initial assessment. Bladder outlet obstruction was defined as a bladder outlet obstruction index (BOOI= pdetQmax-2Qmax) greater than 40 (1). Only men over the age of 40 were included in this group due to the increasing likelihood of a diagnosis of benign prostatic obstruction with age. The other group of patients were those with detrusor underactivity defined by a bladder contractility index (BCI= pdetQmax+5Qmax) of less than a 100(1). Standard pressure-flow studies (PFS) were repeated using the techniques that have remained unchanged in our department since 1972, so allowing direct comparison of results. Machine calibration, reference levels, quality control and trace interpretation were performed according to the recommendations of the International Continence Society (2). Data handling and statistical analysis: Paired t-tests were used to test for differences between initial and follow up BCI. Results are presented in terms of a mean difference together with an associated 95% Confidence Interval (CI). If the test assumptions were found to be untenable, either the Wilcoxon signed ranks test or the sign test was used as appropriate. Analysis of covariance was used to test for differences between the BCI at follow-up assessment for the treated and untreated bladder outlet obstruction groups, adjusting for BCI at initial assessment. Results 196 patients (with a minimum 10 year gap from the first assessment) agreed to have repeat PFS: 56 patients with conservatively treated BOO, none of whom remained on long term drug therapy, 114 patients with BOO treated by transurethral resection of prostate (TURP) and 26 patients had detrusor underactivity. Patients with BOO treated conservatively: Patients’ ages ranged from 40 to 78 with a maximum of 22 year gap from the first assessment. The differences in BCI (follow up – initial) ranged from –132.5 to +60 with a median of –6 (IQR: -24 to 13, n=55). There was no difference in the BCI at follow up compared to the initial BCI (sign test, p=0.10, n=53). Patients with BOO who underwent TURP treatment: Patient’ s ages ranged between 40 and 78 with a maximum of 23 year from the initial PFS. There was no difference between the initial and follow up BCI with a mean difference (follow up – initial) = 0.01, 95% CI: -0.07 to 0.09, n=114.


Comparing the treated and untreated BOO patients, there was evidence to suggest a difference between the follow up BCI for the two groups, with follow up BCI tending to be higher for untreated patients (difference in BCI (untreated – treated) = 23.72, 95% CI: 14.44 to 33.01, n=168), Figure 1. Detrusor underactivity group: the ages of patients in this group ranged from 26 to 66 years, with variable BCI at initial assessment (24-96) and a maximum follow up period of 22 years.

70 80 90 100 110 120 130 140 150 160 170 180 190 200 210 220 230 240

5060708090

100110120130140150160170180190200210220

3

2

2

2

2

2

2

3

33

2

3

3

33

3

2

3

22

3

3

2

2

3

2

3

3

2

3

3 3

3

2

3

3

2

3

3

3

33

3

3

3

33

3

2

32

2

3

2

3

3

3

233

3

23

3

3

3

2

2

3

3

3

3

3

3

2

3

3

3

3

3

2

3

2

3

3

3

3

3

3

3

33

2

2

332

3

3

2

3

2

2

2

33

3

3

2 2

32

2

3

2

23

33

33

3

32

33

23

3

33

3

3

3

3

33

3

2

2

2

2

3

3

3

3

3

3

2

3

3

2

3

2

3

2

2

33

332

3

3

2

2

2

3

BC

I at f

ollo

w-u

p as

sess

men

t

BCI at initial assessment

2=observation from untreated patients 3=observation from TURP patients ------ regression line for untreated patients regression line for TURP patients

Fig 1. There was no difference between the initial and follow up BCI (mean difference (follow up – initial) = 4.42, 95% CI: -3.40 to 12.25, n=26). None of the patients moved into the normal range of BCI (100 or more) during the follow up period. There was no evidence to suggest a relationship between length of follow-up and the difference in BCI (Spearman’s rank correlation coefficient = 0.01, n=26), Figure 2.

di

ffere

nce

in B

CI (

follo

w-u

p - i

nita

l)

length of follow-up (years)10 11 12 13 14 15 16 17 18 19 20 21 22

-35-30-25-20-15-10-505

10152025303540455055

Fig2: Relationship between length of follow up and difference in BCI in DUA

patients.

Fig2. Interpretation of results Patients with untreated BOO showed no significant deterioration of detrusor contractility with time and on the other hand we could not find any significant improvement in detrusor contractility in those treated by TURP. This could be confounded by the long gap between the operation and repeat urodynamic assessment or could be related to how long have these patients had their obstruction before they had their operation. Interestingly, we found that those treated by TURP, had a lower median BCI at the time of follow up, compared to the untreated patients, this is contrary to the detrusor contractility improvement after TURP shown by Porru et al (3). The most interesting results were those from detrusor underactivity patients with no BOO. There was no deterioration in detrusor contractility during the follow up period up to 22 years. It should be noted that these patients came from a wider age range than the BOO patients. Concluding message There is no evidence to suggest that detrusor contractility deteriorates with long-term bladder outlet obstruction. Relieving the obstruction surgically does not improve the contractility, which is important when considering and counselling for TURP operation. Underactive detrusors remains underactive but do not get worse with time which could indicate that it is not an aging process per se and may even have a congenital basis.


References 1. Bladder outlet obstruction index, bladder contractility index and bladder voiding efficiency: three simple indices to define bladder voiding function. Br J Urol Int 1999; 84:14-15. 2. The standardisation of terminology of lower urinary tract function: report from the Standardisation Sub-committee of the International Continence Society. Neurourol Urodyn 2002; 21(2): 167-78. 3. Evaluation of bladder contractility in men undergoing transurethral resection of the prostate. Eur Urol 1996; 30 (1): 34-9. 14 Harding C1, Robson W1, Drinnan M1, Ramsden P 1, Griffiths C1, Pickard R1

1. Freeman Hospital, Newcastle-upon-Tyne, UK VARIATION OF INVASIVE AND NON-INVASIVE MEASUREMENTS OF ISOVOLUMETRIC BLADDER PRESSURE ACCORDING TO BLADDER VOLUME Hypothesis / aims of study Isovolumetric bladder pressure is an accepted measure of bladder contractility and can now be estimated non-invasively by measurement of the inflation pressure required within a pneumatic penile cuff to interrupt voiding (1). Previous studies have suggested that both invasively (2) and non-invasively (3) measured isovolumetric bladder pressure varies with bladder volume, the highest readings being found close to maximum bladder capacity. The use of an automated penile cuff test allows repeated measurements of cuff interruption pressure (pcuff.int) during the course of a single void but the varied values obtained give uncertainty of interpretation. The aim of the present prospective study was to investigate the relationship of simultaneous invasive (pdet.isv) and non-invasive (pcuff.int) measurement of isovolumetric pressure to bladder volume in men with lower urinary tract symptoms (LUTS). Study design, materials and methods Ethical approval and written informed consent were obtained. Men with LUTS attending for conventional pressure-flow studies (PFS) were recruited. Each subject initially underwent PFS according to ICS guidelines for clinical diagnostic purposes. This was then followed by a combined PFS and penile cuff test to give simultaneous invasive and non-invasive pressure measurement. Following a third bladder fill all lines were removed and the penile cuff test was repeated without invasive recording. The voided volume (Vvoid) was recorded at each interruption and normalised as percentage of total voided volume for each subject. Estimation of residual bladder volume was performed at the end of the study using ultrasonography. At each interruption the volume remaining in the bladder was calculated from individual measurements of Vvoid and expressed as a percentage of total voided volume. Values for pdet.isv and pcuff.int were measured from the traces obtained during simultaneous recording at each interruption and grouped according to 20% increments of total voided volume. Values for pcuff.int obtained without invasive recording were analysed separately. Mean [s.d.] values of pdet.isv and pcuff.int were then calculated for each % increment of Vvoid and tested for statistical significance using analysis of variance (ANOVA). Results A total of 30 (83%) patients provided full data acceptable for analysis. The mean (range) number of interruptions was 3.1 (1-6) and the mean [s.d.] total voided volume was 290 [131] mls. The results for mean pdet.isv and pcuff.int for each volume increment showed a gradual rise to 50% voided volume and then fell as bladder emptying continued (Table 1, Figure 1).

% Volume voided 0-20 20-40 40-60 60-80 80-100 ANOVA (p value)

Mean [s.d.] pdet.isv (cmH20)

62 [29] n=13

67 [24] n=17

73 [25] n=13

64 [25] n=19

48 [15] n=32

0.008

Mean [s.d.] pcuff.int (with lines) (cmH20)

102 [38] n=13

111 [24] n=17

120 [28] n=13

115 [41] n=19

86 [26] n=32

0.003

Mean [s.d.] pcuff.int (without lines) (cmH20)

80 [30] n=14

108 [25] n=16

116 [31] n=12

109 [37] n=21

88 [28] n=30

0.001


Values of pcuff,int for each volume increment were similar for cuff tests performed with and without the presence of invasive monitoring (Table 1). At the end of the study no significant residual volume was detected in all but 5 subjects. Interpretation of results These results suggest that the magnitude of isovolumetric bladder pressure measured both invasively (pdet.isv) and non-invasively (pcuff.int) is dependent upon bladder volume in men with LUTS. Highest readings representing maximum contractility occur at approximately 50% of bladder capacity with a slight decrease at higher volumes and a more significant decrease as the bladder empties. The concordance between pcuff.int and pdet.isv throughout the void gives further evidence for the validity of non-invasive measurement of bladder pressure. Interestingly mean values of pcuff.int at each volume increment were similar throughout the void irrespective of the presence of invasive monitoring lines within the urethra. Our data imply that bladder contractility may be underestimated with low Vvoid and support the requirement for a minimum acceptable voided volume for a valid penile cuff test. Concluding message These data from a prospective study of simultaneous invasive and non-invasive measurement of isovolumetric bladder pressure in symptomatic men confirms the variation with bladder volume seen in previous studies using isolated measurements in uncomplaining volunteers and gives further validation of the penile cuff test as a non-invasive urodynamic investigation. Variation in pdet.isv and pcuff.int according to bladder volume when measured simultaneously (dotted lines represent 95% confidence intervals) Figure 1.

References 1 Non-invasive measurement of bladder pressure by controlled inflation of a penile cuff. J Urol 2002;167:1344. 2 Isometric detrusor pressure during bladder filling and its dependency on bladder volume and interruption to flow in control subjects J Urol 1984;131:86 3 Repeated non-invasive bladder pressure measurements with an external catheter. J Urol 1999; 162:474 FUNDING: Action Medical Research 15 Belal M1, Blake C1, Harding C2, McIntosh S2, Griffiths C2, Robson W2, Drinnan M 2, Ramsden P2, Pickard R2, Abrams P1 1. Bristol Urological Institute, 2. Freeman Hospital, Newcastle DETRUSOR CONTRACTILITY IS GREATER IN MALE PATIENTS WITH DETRUSOR OVERACTIVITY Hypothesis / aims of study It has been suggested that detrusor contractility is greater in male and female patients with detrusor overactivity (1) (DO). Accepted methods of assessing detrusor contractility are the isovolumetric detrusor pressure (pdet,isv) and bladder contractility index (BCI). The aim of this study is to test the hypothesis that bladder contractility, measured by pdet,isv and BCI is greater in male patients with DO, independent of the degree of bladder outlet obstruction(BOO). Study design, materials and methods A study was conducted to evaluate the use of a penile cuff (similar to a neonatal blood pressure cuff) inflated during voiding, as a method of determining isovolumetric bladder pressure. (2). As the cuff inflates, it reaches


a point where flow stops. It is at this point that the detrusor contracts against a closed outlet. This represents pdet,isv and is the total pressure measured as shown in the Figure 1.

Figure 1: Measurement of pdet,isv Male patients with LUTS were recruited from two urology departments. A specially designed penile cuff (Mediplus, UK) was placed around the penis and inflated during voiding using the Newcastle technique (2). Once voiding commenced the cuff was automatically inflated until flow was interrupted or a cuff pressure of 200cmH2O was reached. The cuff was deflated to allow voiding to continue. Simultaneous intravesical pressures were recorded using a 6fr double lumen, fluid filled catheter (Mediplus, UK), connected to external pressure transducers in accordance with the recommendations of the ICS standardisation committee. Patients had normal pressure flow studies (PFS) prior to the cuff study, for which the BCI and BOO index was calculated for each patient. Men were classified according to the ICS nomogram as obstructed, equivocal and unobstructed (3). The highest pdet,isv was recorded for each patient. The diagnosis of DO was made on filling cystometry. Results 248 men (mean age 66years, range 20-87) underwent simultaneous cuff test and invasive pressure flow studies. 23 patients were excluded for voiding their urethral catheters and declining recatheterisation, inability to void, equipment failure, missing urodynamics traces, low voided volume and failure of recovery after cuff deflation or failure to interrupt flow. 225 men had data suitable for the analysis for the pdet,isv generated on cuff inflation. 146 had urodynamic proven detrusor overactivity, (mean age 65, range 20-87). 79 had no evidence of detrusor overactivity (mean age 66, range 44-82). A table below shows the distribution of the male patients according to the ICS nomogram and the presence of DO, with the mean and standard deviation of the pdet,isv recorded in table 1and graphically in Figure 2.

DO Group (n=149) Non DO group (n=79)

ICS Nomogram %

pdet,isv cm H20

Mean SD MeanBCI

%

pdet,isv cm H20 Mean SD

Mean BCI

Obstructed 56 108 34 133 38 90 30 133 Equivocal 20 86 39 103 32 66 18 101 Unobstructed 24 76 29 116 30 59 15 116

Table 1 Mean and standard deviation of pdet,isv and BCI for the different groups


0 20 40 60 80 100 120

pdet

isv

(cm

H2O

)

Obstructed

Equivocal

Unobstructed

Combined

ICS

Comparision of pdet,iso between DO and non DO groups

Non DODO

Fig 2 The mean pdet,isv across the different groups A two sample t- test was calculated for all the groups, comparing DO with non DO groups. This showed statistically significance on a 2 tail test in the obstructed, equivocal and unobstructed groups with p=0.01, p=0.02 and p=0.01 respectively. Combination of all the groups showed statistical significance with a 2 tail test with a p value of 0.0001. There was no statistical significance with a 2 sample t-test in the mean BCI between the DO and Non DO groups (p=0.14). Interpretation of results The results show that in male patients with detrusor overactivity there is a higher pdet,isv generated, compared to the non DO group. This holds true for the obstructed, equivocal and unobstructed groups. This shows that in male patients with DO, there is greater detrusor contractility regardless of the degree of BOO. It is interesting that the DO groups did not show a higher BCI. In fact the BCI was highest in the groups where the pdet,isv was highest. The BCI is a theoretical prediction of pdet,isv, but these results show that these 2 measures of detrusor contractility do correlate. The pdet,isv may reflect closer to the maximum detrusor contraction since pdet,isv is at zero flow and all the energy is transferred to detrusor power generation instead of generating flow. Concluding message Isovolumetric detrusor pressure and therefore detrusor contractility is greater in male patients with detrusor overactivity, independent of the degree of BOO. References

1. Different voiding dynamics in stable and unstable bladders with and without outlet obstruction. Neurourology and Urodynamics; 17,473-81 1998

2. Non-invasive measurement of bladder pressure by controlled inflation of a penile cuff. Urol 167, 1344-1347. 2002. 3. The standardisation of terminology of lower urinary tract. Neurourology and Urodynamics, 21, 167-78. 2002.

16 Zimmern P1, Nager C1, Albo M1, Fitzgerald M1, Mohr B1, McDermott S1

1. Urinary Incontinence Treatment Network (UITN) URODYNAMIC INTER-RATER RELIABILITY BETWEEN LOCAL AND CENTRAL PHYSICIAN REVIEWERS FOR THE FILLING CYSTOMETROGRAM IN SISTER (STRESS INCONTINENCE SURGICAL TREATMENT EFFICACY TRIAL) Hypothesis / aims of study Few urodynamic outcomes or inter-rater reliability reports exist from urodynamic studies (UDS) performed at multiple centers. Prior reports from our group demonstrated the need for both standardized testing and


interpretation guidelines 1, and a recent report of an inter-rater reliability study using these interpretation guidelines established excellent intraclass correlation for cystometrogram (CMG) numerical values among four experienced central physician reviewers 2. As part of an on-going quality control (QC) effort to study the inter-rater reliability of UDS performed at multiple centers, we now report a study comparing agreement level between the local physician reviewers (LR) and the four central physician reviewers (CR) for the filling CMG. Study design, materials and methods A standardized testing protocol was implemented study-wide. Standardized urodynamic interpretation guidelines were internally developed, approved by outside expert review, tested for inter-rater reliability in a prior pilot study 2, and formally adopted (7/25/03). Subsequently, 36 urodynamic tracings from 9 centers and 13 different UITN-certified testers were randomly selected. These tracings were read and interpreted by 11 different LR. Each of the 4 CR reviewed 9 randomly assigned CMG tracings. Tracings were electronically transferred to CR from the UITN UDS central repository held at the UITN Coordinating Center. No CR reviewed tracings from his/her own center. LR and CR were instructed to categorize values as “invalid” if specified technical quality assurance standards were not met, or the signal pattern suggested implausible values because of technical deficiencies. Intraclass Correlation Coefficients (ICC) were calculated treating the data as if the LR’s were one rater and the CR’s another. Acceptable agreement was defined a priori as ICC ≥ 0.6. p-values were obtained as a test of the hypothesis that CR mean and LR mean are equal. Results Filling CMG baseline pressure measurements, Valsalva leak point pressure (VLPP) measurements, and volume and pressure measurements at maximum cystometric capacity (MCC) had excellent ICC ranging from 0.74 to 0.99 (table). There were no significant differences between the LR and CR means, indicating excellent agreement.

Description Intra-class correlation Pves at CMG baseline 0.96 Pabd at CMG baseline 0.96 Pdet at CMG baseline 0.97 Mean VLPP 0.99 Volume at MCC 0.74 Pves at MCC 0.96 Pabd at MCC 0.96 Pdet at MCC 0.94

Although detrusor overactivity was also noted by both LR and CR, the relative few instances observed did not permit meaningful statistical calculations. Interpretation of results The urodynamic interpretation guidelines developed for the SISTEr protocol resulted in excellent agreement for critical filling CMG variables between 11 local and 4 central physician reviewers at 9 American medical centers. Concluding message This recent QC study demonstrates that with proper QC measures in place, i.e. well-trained, certified testers; a standard UDS testing protocol with clear annotation of all events occurring during UDS; and a set of standardized interpretative guidelines, excellent inter-rater reliability between LR and CR can be achieved for numerical filling CMG variables. References: (1) SUFU 2003: Urodynamic challenges posed by a multicenter study of surgery for female stress urinary incontinence. (2) SUFU 2004: Urodynamic inter-rater reliability in SISTEr (Stress Incontinence Surgical Treatment-Efficacy Trial). FUNDING: NIH/NIDDK UO1 DK: 58225, 58229, 58231, 58234, 60397, 60380, 60393, 60395, 60397, 60401


17 Rahmanou P1, Chaliha C1, Scholfield D2, Skillern L2, Khullar V1

1. Department of Urogynaecology, St Mary's Hospital, Imperial College, London, 2. Pfizer Ltd RELIABILITY TESTING OF URETHRAL FUNCTION IN WOMEN WITH MIXED URINARY INCONTINENCE. Hypothesis / aims of study Mixed urinary incontinence is a combination of pathologies including detrusor overactivity and urodynamic stress incontinence. This is diagnosed in up to 30% of women attending hospital settings. These women have poorer responses to treatment and it is particularly important to determine tests which will reliably measure urethral and detrusor dysfunction to allow the assessment and development of better treatments. This study attempts to determine the reliability of urethral function tests in women with mixed urinary incontinence. Study design, materials and methods Women were recruited from an urodynamic clinic. All women were diagnosed as having urodynamic stress incontinence and detrusor overactivity on cystometry. Dual channel cystometry was performed with 4 F fluid filled lines in the bladder and rectum. The bladder was filled through a 12 F filling catheter at 100 ml/min. The first sensation to void and maximum bladder capacity were noted. The women were asked to cough every minute during the filling period. Provocative manoeuvres were undertaken to demonstrate stress incontinence at maximum capacity. In the standing position women were asked to cough in a graded fashion, the lowest vesical pressure was regarded as the cough leak point pressure (LPP). Other provocative tests such as running water and hand washing were also performed. Finally the women were asked to void in the sitting position and a pressure flow study was recorded. From this the opening detrusor pressure (ODP) and the closure detrusor pressure (CDP) were obtained. Urethral pressure profilometry (UPP) was performed using the technique described by Hilton and Stanton (1). The maximum urethral closure pressure (MUCP), maximum urethral pressure (MUP), functional urethral length (FUL) and the pressure transmission ratio (PTR) in quartiles were all calculated. A 24-hour pad test was also carried out. Two weeks later all the tests were repeated. The precision and bias of the tests was measured using the method of Altman and Bland (2). The Coefficient of Repeatability value allows direct comparison of repeatability of each test, with a lower value indicating less variation. Results 17 women who were diagnosed with mixed incontinence in at least one of the tests were recruited. 11 women had mixed incontinence in both tests. The pad test was not completed by 18% of the women. 35% of subjects were not able to produce cough LPP on both visit. Otherwise all the women completed the rest of the tests. Table 1. Subjects with urodynamic mixed incontinence

Tests Mean (SD) Mean Difference (SD) CR

ODP (cmH2O) (n=17) 17.09 (8.26) 0.06 (9.85) 19.3

CDP (cmH2O) (n=13) 21.40 (14.27) -4.92 (21.86) 42.8

Cough LPP (cmH2O) (n=11) 138.36 (55.18) -6.36 (38.78) 77.6

MUCP (cmH2O) (n=17) 48.29 (24.51) -10.71 (23.26) 45.6

MUP (cmH2O) (n=17) 68.44 (23.17) -9.71 (20.03) 39.3

FUL (cmH2O) (n=17) 2.874 (0.60) 0.006 (0.64) 1.3

PTR Q1(%) (n=17) 101.68 (35.42) 20.41 (49.46) 96.9

PTR Q2 (%) (n=17) 96.88 (23.82) -12.24 (37.78) 74

PTR Q3 (%) (n=17) 89.79 (19.08) 0.18 (27.40) 53.7

PTR Q4 (%) (n=17) 78.03 (25.95) -0.18 (28.71) 56.3

Pad test (g) (n=14) 130.03 (329.67) -18.89 (30.86) 60.5


5.00 10.00 15.00 20.00 25.00 30.00Mean ODP (cmH2O)

-30.00

-20.00

-10.00

0.00

10.00

20.00

30.00Difference in ODP (cmH2O)

Mean + 1.96 SD

Mean - 1.96 SD

Mean

20.00 30.00 40.00 50.00 60.00 70.00 80.00 90.00

Mean MUCP (cmH2O)

-75.00

-50.00

-25.00

0.00

25.00

50.00Difference in MUCP (cmH2O)

Mean + 1.96 SD

Mean

Mean - 1.96 SD

Fig 1: The difference between ODP measurements against the mean value Fig 2: The difference between MUCP measurements against the mean value

50.00 100.00 150.00 200.00Mean cough LPP (cmH2O)

-100.00

-50.00

0.00

50.00

100.00Difference in cough LPP (cmH2O)

Mean + 1.96 SD

Mean

Mean - 1.96 SD

0

10

20

30

40

50

Visit 1 Visit 2

cmH

2O

Fig 3: The difference between cough LPP measurements against the mean value. Fig 4: ODP measurements at different visits Interpretation of results Measurements of urethral function show poor repeatability. The best of these tests appear to be FUL, ODP and MUP. Concluding message All tests of urethral function show great test retest variation in women with mixed incontinence. This is may be because urethral function is affected in the presence of detrusor overactivity. References 1. Br J Obstet Gynaecol. 1983 Oct; 90(10): 919-33. 2. The Lancet. 1986: i; 307-310. FUNDING: Pfizer Limited 18 Mueller E1, Kenton K1, Mahajan S1, Fitzgerald M P1, Brubaker L 11. Loyola University Medical Center STRIATED URETHRAL SPHINCTER ACTIVITY IS NOT AFFECTED BY PELVIC ORGAN PROLAPSE DESPITE CHANGES IN MAXIMAL URETHRAL CLOSURE PRESSURE. Hypothesis / aims of study Advanced pelvic organ prolapse has been associated with a variety of lower urinary tract symptoms ranging from stress urinary incontinence to urinary retention. Previous authors have demonstrated increases in


maximal urethral closure pressures (MUCP) in women with advanced pelvic organ prolapse when compared to women with stress urinary incontinence1. This finding has lead to speculation that anatomic effects from the prolapse on the urethra may result in a “functional urethral obstruction”, which results in urinary retention. Electromyography is the “gold standard” for evaluating neuromuscular function throughout the body. A recent study demonstrated that changes in MUCP were not as sensitive as changes in quantitative EMG during filling cystometry, suggesting that EMG more accurately reflects striated urethral sphincter activity2. There are no published studies investigating the neuromuscular activity of the striated urethral sphincter using quantitative EMG in women with advanced pelvic organ prolapse. The aim of our study was to determine the relationship between MUCP and quantitative EMG of the striated urethral sphincter in women with advanced prolapse.

Study design, materials and methods Women with stage III or IV prolapse undergoing multichannel urodynamic testing with concentric needle EMG were invited to participate in this IRB approved study. Maximum urethral closure pressures and quantitative EMG of the striated urethral sphincter were obtained at the subject’s maximum cystometric capacity with the prolapse maximally everted (unreduced) and reduced. Subjects were randomized to the order in which MUCP and EMG measurements were obtained (reduced or unreduced). Maximum urethral closure pressures were obtained on a Life-Tech urodynamic instrument (model 1106, Life-Tech, Inc, Houston, TX) with an 8F dual- microtipped catheter (Millar Instruments, Houston, TX). The proximal transducer was positioned in the urethra facing 9-o’clock with the profilometer set at a withdrawal rate of 1mm per second. A 30 gauge, concentric needle electrode was placed 5mm above the external urethral meatus at the 12 0’clock position in the striated urethral sphincter. Correct needle placement was confirmed using oscilloscope and auditory guidance. Raw EMG signals were processed by a Nicolet Viking IVp electrodiagnostic instrument (Nicolet Instrument Corportation, Madison, WI) equipped with automated motor unit analysis software programs. Quantitative EMG software was used to analyze electrical activity of the striated urethral sphincter with the prolapse reduced and unreduced. The sign test was used to evaluate differences in MUCP and quantitative EMG with the POP reduced and unreduced. Results were considered significant at the 5% level. Results Twenty-three women were included in the study with a mean age of 59 years (range 36-74). All had advanced prolapse (83% stage III and 17% stage IV), and most were Caucasian (83%). Sixty-four percent had urodynamic stress incontinence. Maximum urethral closure pressures with the prolapse unreduced were significantly higher than MUCP reduced; however, quantitative EMG values of the striated urethral sphincter were not different with the prolapse reduced and unreduced. Reduced Unreduced P- value MUCP 40cmH2O (31-61)* 60cmH2O (46-96)* .001 Quantitative EMG 12µV (7-15)* 11µV (9-20)* .804 *values represent median and 25th to 75th quartile range Interpretation of results These findings suggest that the increase in MUCP associated with advanced prolapse is not due to an increase in the neuromuscular activity of the striated urethral sphincter. The increased urethral pressure, and possibly, urinary retention associated with advanced prolapse may be due to anatomic effects from the prolapse and not reflex activation of the striated urethral sphincter. Concluding message Maximum urethral closure pressures do not accurately reflect the neuromuscular activity of the striated urethral sphincter in women with advanced prolapse. Pelvic organ prolapse results in elevated MUCP, which are not related to increased neuromuscular activity in the striated urethral sphincter.

1. Richardson DA, Bent AE, Ostergard DR, The effects of uterovaginal prolapse on urethrovesical pressure dynamics. Am J Obstet Gynecol 146:901, 1983

2. Striated urethral sphincter activity does not alter urethral pressure during filling cystometry. Am J Obstet Gynecol, submitted


19 Krause H1, Goh J1, Forward M2, Bennett M2

1. Royal Women's Hospital, 2. University of Queensland BIOMECHANICAL PROPERTIES OF MESHES Hypothesis / aims of study Synthetic meshes are becoming more popular in incontinence and prolapse surgery. Previous studies have tested meshes to failure, which is non-physiological, and the effect of strain rate was not clearly defined and the elastic modulus was obtained at high stress levels. The aims of this study are to assess the biomechanical properties of commonly used meshes in urogynaecological surgery. Study design, materials and methods Nine different types of meshes used in urogynaecological surgery were examined using uniaxial tensile tests. Each sample comprised a rectangle of mesh, the ends of which were gripped between flat steel plates and mounted on an Instron 8872 servo-hydraulic materials testing machine. A 250 newton dynamic load cell was used to measure the forces applied to the samples under tests to failure using ramp tests or when exposed to cyclical length change. The test length (distance between clamps) was standardised at 32mm for all samples. Results Tensile ramp loading to failure was conducted at an actuator displacement rate of 2 mm s-1. Of the 9 mesh types, 6 tended to fail in a single catastrophic event (Atrium, IVS, Prolene, SPARC, TVT and Vypro II), whereas 3 (Dexon, Gynemesh and Vypro) tended to undergo multiple failure events prior to finally parting. Table 1 presents the mean load at which the first major failure event occurred (defined here as an abrupt ≥ 10% reduction in load) and the ultimate load achieved by each mesh type. The percent strains at which these events occurred are also given. It is obvious that the strength and extensibility of the mesh designs differed considerably. Prolene was the strongest, at about five times the strength of Vypro II. IVS and Vypro were the least extensible mesh designs, only able to increase in length by about 50%, whereas TVT, Dexon and SPARC were able to withstand a doubling of their original length without failing. Most mesh types exhibited curvilinear loading curves, in which the material stiffness started at relatively low levels, increased with increasing extension to finally become linear (relatively high stiffness). Prolene and IVS were the exceptions, with IVS displaying an initial, relatively high stiffness that gradually declined with further extension and Prolene had the same initial pattern, but changed to a high linear stiffness above about 50% of its failure strain. Cyclical loading of mesh samples (20 ± 5 % strain, 1 Hz, 15 sinusoidal loading cycles) produced significant permanent deformation in all mesh designs. This non-recoverable extension ranged from about 8.5 % (SPARC) to 19 % strain (Dexon). At the levels of strain applied to the mesh samples the minimum loads experienced by the samples was broadly similar (range 0 – 3 N), whereas the peak loads varied markedly (Table 1). Hysteresis also varied considerably between materials, approaching 85% in Vypro II and as little as about 30% in IVS. Interpretation of results Previous examinations of full thickness anterior vaginal wall samples have demonstrated tensile strains of between 19 and 31% under applied stresses of 0.4 megapascals (a stress that all tissues could withstand (1). The results from tensile tests on these 9 meshes indicate that all are capable of such deformations without compromise. The stiffness profiles of some mesh types do, however, differ significantly from those for vaginal. As tested here, Atrium, IVS, Prolene and Vypro would appear to provide moderate to high levels of stress-shielding to repaired tissues. Dexon, TVT and Vypro II appear to be over compliant at low loads, with Gynemesh and SPARC having intermediate properties.

Table 1. Physical and mechanical properties of the nine mesh types studied. Load (N) Strain (%) Mesh Type Mean Mesh Width

(mm) Ultimate First Major Failure

Ultimate First Major failure

Load at 25% strain (N)

Offset (mm)

GYNEMESH 12 37.5±1.0 37.5±1.0 63.4±0.8 63.4±0.8 10 3.2 TVT 11.5 77.0±3.7 70.8±9.3 113.4±3.0 111.6±4.6 3 3.5 PROLENE 12.4 122.0±2.8 122.0±2.8 66.6±1.8 66.6±1.8 16 4 SPARC 10.9 66.8±6.7 66.8±6.7 135.3±7.2 135.3±7.2 4.1 2.7 VYPRO 14.2 100.0±1.4 81.7±2.9 74.1±2.3 57.2±2.3 25 5 DEXON 14 105.8±7.0 78.0±11.5 125.3±5.6 110.0±7.9 0.1 6 VYPRO II 12.2 24.5±1.0 24.5±1.0 81.3±5.4 81.3±5.4 0.7 4 ATRIUM 12.5 95.4±7.3 95.4±7.3 80.3±2.6 80.3±2.6 13 4 IVS 8.1 50.8± 50.8± 47.8±2.9 47.8±2.9 3 3.8

n= 4 for all tests


Concluding message This paper provides further information on the mechanical properties of each of these 9 mesh designs. Further invivo studies are required to assess the effect of implanted meshes on biomechanical properties of tissues. References 1. A new method to measure properties of plastic-viscoelastic connective tissue. Med Engin Phys 1998; 20(4): 308-314. 20 Krause H1, Goh J1, Khoo S K2, Williams R3, Galloway S3

1. Royal Women's Hospital, 2. University of Queensland, 3. St Vincent's Hospital BIOCOMPATIBLE PROPERTIES OF SURGICAL MESH USING AN ANIMAL MODEL Hypothesis / aims of study Meshes have been used in prolapse and incontinence surgery for some time now without significant research or clinical data to support its use. Types of mesh vary substantially with regard to composition of the fibres, type of weave, pore size, tensile strength, and flexibility of the material. Pore size and mesh weight are considered key factors in determining the inflammatory response and growth of fibrocollagenous tissue. Macroporous mesh is thought to allow rapid ingrowth of vascularised fibrous tissue. This causes fibroplasia and angiogenesis which is said to prevent infection and form fibrous connections to surrounding tissue. Smaller pore sizes may be inadequate as this may prevent capillary penetration. The aim of this study is to compare the biocompatibility of 8 surgical meshes (used in urogynaecological surgery) in an animal model. Study design, materials and methods Animal Ethics committee approval was obtained prior to commencing the study. The meshes employed were polypropylene meshes (Atrium, Gynemesh, Prolene), mixed fibre mesh (Vypro II), delayed absorbable polyglactin mesh (Dexon) and mid-urethral sling meshes (TVT, SPARC, IVS). Meshes were implanted onto the sheath of the abdominal wall of 40 male Sprague-Dawley rats at 70 days of age. Meshes were implanted in a standardised manner on the right of the midline of the abdomen, over intact fascia. The left had side of the abdominal wall on each rat acted as the control. The meshes were explanted (with fascia intact) after 12 weeks and stained with haematoxylin and eosin. Light microscopy was used to assess parameters of rejection and incorporation. An independent pathologist blinded to the mesh types, assessed the sections and graded the parameters qualitatively. Inflammation was evaluated histologically, by estimating the amount of macrophages and inflammatory cells present. Interobserver and intraobserver comparisons were undertaken to ensure reproducibility of results. Results Type 3 (multifilamentous macroporous) IVS mesh had the most marked fibrosis surrounding the fibres compared to Type 1 (monofilamentous macroporous) meshes which were noted to have a moderate fibrotic response. Type 3 meshes (Dexon and IVS) had a higher proportion of the mesh interface perimeters surrounded by giant cells. All Type 1 meshes were able to be grouped together by mesh pattern as clusters of course fibres with some spaces between them. Type 3 meshes were all identified to have bundles of closely spaced fine fibres. Absorbable meshes (Dexon and polyglactin components of Vypro2), had both remnants of fibres and intact fibres present. Interpretation of results Histological assessment of explanted mesh tissue has demonstrated differences between Type 1 and Type 3 meshes. The marked fibrosis demonstrated in Type 3 meshes may be a result of a more intense inflammatory reaction. It is well described that heavy-weight meshes provoke a more pronounced inflammatory reaction. IVS is of heavier weight than the Type 1 meshes assessed here. In addition, polyglactin is well known to induce a vigorous fibroblastic reaction (1). Thus the quite moderate fibrosis noted in the Dexon material is not surprising. Despite this, the strength of the induced scar tissue formed over polyglactin mesh is lost over time as demonstrated with previous abdominal mesh hernia studies. A reduction in mesh weight and an increase in pore size can reduce inflammatory activity which may be beneficial. Excessive fibrosis can result in reduced tissue flexibility. The large pore size mesh is integrated in a loose network of tissue which includes the pores


(2). The more intense giant cell reactions in the Type 3 meshes may indicate a less favourable response in the long- term, however assessment over time is required to determine eventual outcome of this response. Concluding message Type 1 polypropylene meshes demonstrate different characteristics to the Type 3 IVS mesh, namely, less marked fibrosis at the interface of mesh and host tissue. Additional fibrosis has not proven in other studies to give added benefit to the repair, and this may be a detrimental effect as tissue flexibility may be reduced. Biomechanical testing on these tissues may provide correlation on tensile strength to histological appearance. Reference 1. Influence of polyglactin-coating on functional and morphological parameters of polypropylene-mesh modifications for abdominal wall

repair. Biomaterials 1999; 20: 613-623. 2. Impact of polymer pore size on the interface scar formation in a rat model. J Surg Res 2002; 103: 208-214. 21 Moore R1, Miklos J1, Knoll L D2, Dupont M3, Winkler H A4, Lind L4, Kohli N5, Serels S6, Karram M7, Walters M8, Davila W9 1. Northside Hospital, 2. Center for Urological Treatment, 3. Dupont Center for Urology/Urogynecology, 4. North Shore University Hospital, 5. Brigham & Women's Hospital, 6. Urology Associates of Norwalk, 7. Good Samaritan Hospital, 8. Cleveland Clinic, 9. Cleveland Clinic Florida PRELIMINARY PROCEDURAL AND SAFETY DATA FROM THE UNITED STATES CLINICAL STUDY ON THE AMS MONARC™ SUBFASCIAL HAMMOCK Hypothesis / aims of study In recent years, sub-urethral sling placement has become a standard treatment for Stress Urinary Incontinence (SUI). A United States clinical trial was launched in July 2003. The goals of the study were to show reduced morbidity in vascular/bladder/bowel injuries that are related to the retropubic approach, examine the neurological effects of passing the Monarc needles through the obturator foramen, and determine subjective and objective efficacy of the Monarc Subfascial Hammock. Study design, materials and methods Pre-operative urodynamics, and pre and post-op Q-Tip Test, Cough Stress Test, One-hour pad test, 3-day voiding diaries, Quality of Life Questionnaires and a Motor, Sensory and Pelvic Exam were performed. Physicians and subjects assessed degree of continence attained post-operatively. Intra-operative data included concomitant repairs, operative time, blood loss, cystoscopy results, time to void without catheter and complications. Subjects will be followed at 4-6 Weeks, 6 Months and 12 Months. During the Motor, Sensory and Pelvic Exam, the physician performed a general pelvic examination, noting any abnormalities or prolapse conditions. For the sensory portion, a bilateral light touch and pinprick exam was done of the mons, labia, perianal area, and medial thigh. The patient was asked to assess pain and tenderness using the visual analogue scale (0=No Pain, 10=Worst Possible Pain) with palpation of the adductor muscle/proximal tendon, passive abduction, resistance adduction, passive external rotation of the hip, resistance internal rotation of the hip, and assessment of gait. Results Between July 2003 and March 2004, 47 patients were implanted with the Monarc hammock. Mean operative time was calculated for three circumstances:

Circumstance Number of Patients

Mean Op time (minutes)

Range (minutes)

Monarc procedure only 37 14.7 5-30

Monarc procedure + concomitant repairs 5 31.4 12-70

Patients Implanted at teaching hospital (residents participating in procedure)

5 36 23-39


Average blood loss was 32.8 ml (2-150ml). Intraoperative cystoscopy was performed on 46 patients (98%) and no bladder perforations were reported. Mean time to void without catheter was 10.8 hours (0-32 Hr) and 43 patients (91.5%) went home without a catheter. 39 patients completed 4-6 week follow-up visits. Both physician and patient assessments of the level of continence attained reported 33 (85%) patients being substantially or totally continent. There were 7 adverse events (AEs) reported in 3 patients (6.4% of total patients). Two of the AEs were device-related: One patient reported musculoskeletal pain, which is ongoing and is being treated with medication. One patient reported urinary retention; the patient was catheterized and the event resolved in two days. The same patient also reported dehydration, increased chronic cough, post-op abdominal pain (all of which have resolved). The physician feels that these AEs were due to the concomitant repairs performed during Monarc placement surgery and are not device related. Two patients reported two additional non-device related events: atrial fibrillation (treated with medication, resolved) and bacterial vaginosis (treated with antibiotics, ongoing). 1/47 patients (2.1%) failed the procedure; the sling was removed, and another procedure was performed. The Motor, Sensory, and Pelvic Exam Results

Pre-Operative (n=47) 4-8 Weeks (n=35) Exercise Left Left Right Right Left Left Right Right

Average Pain/Tenderness Average Range of Motion

Pain or

Tenderness

RO

M

(degrees)

Pain or

Tenderness

RO

M

(degrees)

Pain or

Tenderness

RO

M

(degrees)

Pain or

Tenderness

RO

M

(degrees)

Palpation of adductor muscle + proximal tendon 0 N/A 0 N/A 0 N/A 0 N/A

Passive abduction 0.2 45.1° 0.0 44.7° 0 44.5° 0.1 45.1°

Resistance adduction 0 N/A 0 N/A 0 N/A 0.1 N/A

Passive external rotation of hip 0.1 43.3° 0.0 43.6° 0 44.2° 0 44.2°

Resistance internal rotation of hip 0.8 N/A 0.0 N/A 0 N/A 0 N/A

Assessment of Gait 0.2 N/A 0 N/A 0 N/A 0 N/A

ROM=Range of Motion Interpretation of results There were no vascular, bladder or bowel injuries reported, and no intra-operative complications. Blood loss was minimal and most patients went home without a catheter. It appears that neurological function and range of motion is not affected by passing needles through the obturator foramen. By mimicking the natural position of the pubourethral ligament, we believe we reduce the post-operative risk of urinary retention. Concluding message By avoiding the vessels and nerves of the retropubic space, the Monarc offers a relatively quick procedure that proves to be safe and effective. These initial results show that the transobturator approach may be safer than the traditional retropubic approach to the tension free mid-urethral sling. Further follow-up is needed. FUNDING: American Medical Systems


22 Waltregny D1, Reul O1, Bonnet P1, de Leval J1

1. University of Liege INSIDE-OUT TRANSOBTURATOR VAGINAL TAPE (TVT-O): SHORT-TERM RESULTS OF A PROSPECTIVE STUDY Hypothesis / aims of study The aim of this study was to prospectively evaluate the efficacy of the TVT-O inside-out procedure for the treatment of female stress urinary incontinence (SUI). Study design, materials and methods From March 2003 through September 2003, 53 patients with clinical evidence of SUI participated in this prospective clinical trial. Preoperative evaluation included complete history, physical examination, multichannel urodynamics, urine analysis, and cystoscopy. None of the patients presented the following exclusion criteria: post-void residual volume (PVR) ≥ 100 cc, detrusor overactivity or acontractility, contraindication to anesthesia, pregnancy, neurological pathology, or active urinary or vaginal infection. All patients met the following inclusion criteria: age > 25 and < 85 years, clinically demonstrated SUI, positive Ulmsten test, and maximum cystometric capacity ≥ 300 mL. In all patients, a sub-urethral tape (Gynecare®) was inserted by one single surgeon via an inside-out transobturator approach (TVT-O), as previously described (1). Evaluation of SUI, urgency/urge incontinence, daytime urinary frequency/nocturia, and lower urinary tract symptoms (LUTS) suggestive of bladder outlet obstruction/retention was carried out using the Measurement of Urinary Handicap scale questionnaire (2). The importance of urinary incontinence was assessed with a visual analog scale graded from 0 to 10. Quality of life (QoL) assessment was performed using the validated Ditrovie self-administered questionnaire. Outpatient follow-up was perfomed at 1 and 6 months, and every 6 months thereafter. Follow-up evaluation included physical examination with a stress test, uroflowmetry, PVR, and symptom, visual analog, and QoL scales scoring. Cure was defined as no leakage based on both symptom scale scoring and physical examination. Improvement was defined as at least a 50% decrease in symptoms based on the questionnaire’s evaluation. Chart review was conducted by a physician not associated with the origical procedure. The specific protocol used in this study was approved by the Medical Ethics committee of our Institution. All patients had given their written informed consent. Methods, defintions,and units conform to the standards recommended by the ICS. Results Mean age of the patients was 61.2 years (36 to 80). Of the 53 patients, 20 had undergone previous pelvic surgery. Forty-eight patients suffered from SUI. Five patients did not complain of SUI but had clinical evidence of SUI after reduction of pelvic organ prolapse (POP) during vaginal examination. The TVT-O procedure was associated with POP cure (performed before TVT-O) in 12 patients. Maximal urethral closure pressure was < 30 cm H20 in 6 patients. Follow-up time was ≥ 6 months in all women (max = 12.5; mean = 8). A total of 33 and 20 women received spinal and general anesthesia, respectively. Intraoperative blood loss was < 100 cc in all cases. No vaginal wall, urethral, or bladder perforation was encountered. No hematoma, neurological complication, fistula, vaginal or urethral erosion, or tape rejection was observed. Some patients reported pain symptoms, directly after the procedure, mainly located in the thigh regions (either uni- or bilaterally). Pain was always mild, never requiring opioid antalgics. No patient complained of persistent pain; indeed, pain had completely vanished within the first post-operative month in all cases. At the latest follow-up visit, PVR was < 100 cc and max flow rate was ≥ 10 mL/sec in 49 (92.4%) and 39 (73.6%) patients, respectively. One patient underwent an immediate tape release procedure for complete retention 2 days after TVT-O. Thereafter, the patient had no PVR and was completely dry. The tape was sectioned in 2 patients for chronic retention and/or urgency associated with bladder outlet obstruction, 4 and 7 months after the operation. Based on the SUI questionnaire evaluation and physical examination, 50 (94.3%) patients were cured. SUI symptoms had improved in 1 patient and had not changed in another. One patient with POP not complaining of SUI preoperatively (but with clinically demonstrated SUI following POP reduction) developed SUI after POP cure associated with TVT-O. Analysis of the urgency questionnaire’s results revealed that among the 53 patients, 32 did not complain of any urgency before the operation. Of these 32 patients, 3 patients developed de novo urgency, with one of them requiring tape sectioning because of obstruction-associated urge incontinence. Among the 21 patients with preoperative urge symptoms, 15 of them reported disappearance of urgency after the procedure. Urge symptoms were unchanged in the remaining 6 patients. Daytime frequency/nocturia symptoms scale scoring showed that 4 patients had a worsening of these symptoms while all other patients


were either improved or unchanged. LUTS suggestive of bladder outlet obstruction/retention appeared or worsened in 3 patients, amongst which the 2 patients who required tape sectioning. These symptoms were unchanged or decreased (mainly in patients with associated POP cure) in all other patients. Analysis of the urinary incontinence visual analog and QoL scale scores demonstrated that the majority of patients reported disappearance of urinary leakage together with significant improvement of their QoL (Figures 1 and 2). Interpretation of results As already suggested by the results of a recent feasibility study (1), TVT-O appears to be associated with a minimal risk of peri-operative complications. Indeed, in our present prospective study, no injury to the bladder, vagina, or urethra was encountered and we have not observed any vascular, digestive or neurological complication. Our data suggest that TVT-O is associated with high objective and subjective SUI cure rates and a low incidence of post-operative complications. Longer follow-up times are required to determine the long-term efficacy of TVT-O.

Figure 1: Urinary incontinence visual analog scale scores

0

1

2

3

4

5

6

7

8

9

10

Preop Postop

n=1

n=1

n=1

n=1

no leak

permanent leak

Figure 2: QoL scale scores

1

2

3

4

5

Preop Postop

n=1

n=1

n=1

best

worst

Concluding message The short term results of this prospective study suggest that TVT-O is a safe and efficient surgical procedure for the treatment of female SUI. References 1. Novel surgical technique for the treatment of female stress urinary incontinence: Transobturator vaginal tape inside-out. Eur Urol 44:724-730, 2003 2. Elaboration and validation of a specific quality of life questionnaire for urination urgency in women. Prog Urol 7:56-63, 1997 23 Schraffordt S1, Bisseling T2, Heintz P3, Vervest H2

1. Meander Medical Centre, 2. Elisabeth Hospital Tilburg, 3. University Medical Center Utrecht DOES TENSION CHANGES THE OUTCOME OF TVT? A PROSPECTIVE MULTICENTRE STUDY OF 809 PATIENTS. Hypothesis / aims of study In the original article of Ulmsten and Petros (1) the authors stress on the fact that “no elevation whatsoever was done” during the procedures described. This to prevent “passive kinking of the urethra”. The aims of this study were to investigate whether the tension put on the TVT by the surgeon changes the final outcome on urinary stress incontinence (USI), urge incontinence and obstructive micturition.


Study design A multi center prospective cohort study of 809 patients undergoing a TVT procedure. The current follow-up is two years. Materials and methods Between March 2000 and September 2001, patients with an indication for the TVT procedure were asked to participate in this study. The procedures took place in 41 different hospitals in which 54 gynecologists and urologists performed the TVT procedure. Among the 41 hospitals there were 3 university hospitals, 25 teaching hospitals and 13 local hospitals. All participating gynecologists and urologists were qualified to perform vaginal surgery and had a short training in performing TVT’s by an experienced surgeon. Inclusion criteria were stress urinary incontinence (SUI) with an indication for surgery. Exclusion criteria were: recurrent and difficult to treat urinary tract infections, significant symptoms of urge urinary incontinence, a history of or detrusor over activity at cystometry, post voiding bladder retention (>150 ml), bladder capacity less than 200 ml or a physical/mental impairment. The operation was carried out under local anesthesia using 0.25% prilocaine with adrenalin and sedation, spinal analgesia or general anesthesia. Directly post operative the surgeon was asked to fill out a form in which he or she stated the amount of tension he or she put on the TVT (lose, moderate or tight). The outcome of the TVT’s was measured with a disease specific HRQOL questionnaire the Urogenital Distress Inventory (UDI). Uebersax et al. (2) validated a short form for this questionnaire (UDI-6). These questionnaires were translated and validated in the Dutch language by van der Vaart (3). Patients received the postal questionnaires: preoperative, 12 and 24 months after surgery. As outcome variables the subscales stress incontinence, irritative and obstruction of the UDI were taken. The subscale stress comprises two questions: Do you experience, and if so, how much are you bothered by: 1 leakage related to activity, coughing, or sneezing and 2 small amounts of leakage (drops). The subscale for irritative comprises the questions: Do you experience, and if so, how much are you bothered by: 1 frequent urination, 2 leakage related to feeling of urgency. The subscale for obstructive/discomfort comprises the questions: Do you experience, and if so, how much are you bothered by: 1 difficulty emptying bladder, 2 pain or discomfort in lower abdominal or genital area. The answers give points on a 0-100 scale where 100 means the most bothersome and 0 no symptoms at all. Results Of the initial 809 patient we received results from 688 patients on the tightness of the tape (85%), group 1 (tape lose) 257 patients (37.4%), group 2 (tape moderate) 393 patients (57.1%) and group 3 (tape tight) 38 patients (5.5%). The follow-up after 2 years was for all 3 groups 76%. Patient characteristics as well as preoperative scores for the UDI were comparable between the three groups. Table 1 shows the scores on the UDI for the three different groups. No significant difference was found between the 3 groups. Table 1: UDI SCORES tape tape tape sign lose moderate tight preoperative subscale irritative 64.8 68.1 67.1 0.306 subscale stress 75.0 77.0 77.6 0.485 subscale obstruction 32.2 32.8 30.1 0.801 1 year postoperative subscale irritative 28.6 28.7 36.5 0.298 subscale stress 12.6 12.7 18.5 0.314 subscale obstruction 22.7 22.8 20.8 0.902 2 years postoperative subscale irritative 31.1 29.5 34.8 0.578 subscale stress 15.0 16.5 17.4 0.717 subscale obstruction 25.0 23.3 25.0 0.740 One-way ANOVA, Post Hoc Bonferroni test * Significant P-value < 0.05 The values presented are the mean scores on the UDI subscales. A high score means more bother.


Interpretation of results The values in Table 1 are the scores on the different subscales. The points are on a 0-100 scale where hundred means the most bothersome and zero no symptoms at all. There are no significant differences in UDI scores between the lose, moderate and tight tape groups. The subscale scores are comparable between the three groups before surgery as well as 1 year and two years post operative. Concluding message A tight, moderate or lose placement of the TVT underneath the urethra, as reported by the surgeon, has no effect on the final result for stress incontinence, postoperative urge incontinence or obstructive micturition. References 1 Ulmsten U, Petros P. Intravaginal slingplasty (IVS): an ambulatory surgical procedure for the treatment of female urinary

incontinence. Scand J Urol Neprol 1995;29:75-82 2 Uebersax JS, Wyman JF, Shumaker SA, McClish DK, Fantl JA, and the Continence Program for Women Research

Group. Short form to asses life quality and symptom distress for urinary incontinence in women: the incontinence impact questionnaire and the urogenital distress inventory. Neuro Urodyn 1995;14:131-139.

3 Vaart van der CH, Leeuw de 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. Neuro Urodyn 2003;22:97-104.

24 Birch C1, Fynes M2

1. St. George's Hospital Medical School, 2. t. George's Hospital Medical School MESH EROSION COMPLICATING VAGINAL SURGERY FOR THE CORRECTION OF POSTERIOR COMPARTMENT PROLAPSE Hypothesis / aims of study To evaluate the incidence and management of mesh erosion following vaginal surgery for the correction of recurrent posterior compartment prolapse. Study design, materials and methods Between 01.09.2001-01.09.2002 all women undergoing Bilateral iliococcygeus fixation (BIF) and posterior fascial repair (PFR) with polypropylene mesh interposition for recurrent recto-enterocele and rectocele were evaluated. Peri-operative details including age, parity, menopausal status, HRT usage and previous prolapse surgery. In each case a standard prolapse symptom questionnaire was completed and vaginal examination undertaken to evaluate integrity of the vaginal tissues and genital support using the modified Baden Walker classification system. PFR with mesh interposition was performed in an identical manner with the exception of the BIF. BIF fixation was performed using a modification of the description by Immon (1963). In each case antibiotics were administered (Metronidazole and Cephadrine) intra-operatively and catheter drainage performed for 24-48 hours following surgery. All women were followed up at 6 weeks, 6 and 12 months following surgery. At follow-up symptoms of prolapse, pain, dyspareunia, discharge and bleeding were recorded and examination performed to assess vaginal support and exclude mesh erosion. Where erosion was identified the site and extent of the defect were recorded. Those with erosion were treated with oral antibiotics and topical oestrogen therapy for a minimum of two weeks. Where the erosion failed to re-epithelialise surgical intervention was undertaken. The decision to 1) oversew, 2) trim and oversew or 3) excise and oversew was at the discretion of the surgeon and dependant on the size of the eroded area and the integrity of the vaginal tissues. All women were continued on antibiotics and topical oestrogen following surgery. Where persistent mesh erosion was identified then re-excision of as much mesh as possible was performed. All women affected were followed up at regular intervals. Analysis of risk factors was performed for women who sustained an erosion compared to those who did not. Results Twenty-one women underwent a BIF and 5 a PFR with polypropylene mesh interposition. All of these women had a recto-enterocele or rectocele ≥ Grade 2 and had undergone one or more previous prolapse operations.


Mesh erosion was identified in 10/21(48%) following BIF and 1/5(20%) following PFR (p=0.5, Yates corrected Chi squared test). The mean age for those affected was 61 years (R51-73) and mean parity 3(R2-4). Five (45%) were on HRT and 4(36%) had significant vaginal atrophy prior to prolapse surgery. Only 6(55%) were sexually active. Most erosions were symptomatic and occurred early following surgery. The mean duration to recognition was 5.5 months (R2-13). In women who had undergone a BIF procedure the most common site of erosion was in the upper third of the posterior vaginal wall midway between the sites of fixation to the iliococcygeus fascia. There were no significant differences between these parameters for women who sustained a recognised erosion compared to those who did not. The mean intra-operative blood loss for those who sustained mesh erosion was 650mls (R 50-4000). Two women who developed subsequent erosion had an estimated blood loss in excess of 1000mls. One of these was also complicated by significant vaginal infection. All women were treated with topical oestrogen and antibiotics. At follow-up in two cases the vagina had re-epithelialised. In both of these cases only a small number of mesh fibers were exposed. The remaining eight required surgical correction and of these 3 required repeat excision and oversew . At a mean of 12.2 months (R7-15) no woman had a recurrence of rectocele or enterocele > grade 1. Interpretation of results In this study most women undergoing recurrent prolapse surgery with mesh re-inforcement were postmenopausal and not taking HRT. Despite this there were no significant differences in age, oestrogen status or HRT usage between those who sustained an erosion compared to those who did not. There were insufficient numbers of younger women however, to positively exclude these parameters as contributory factors. Although only one woman had evidence of frank vaginal infection prior to erosion of the mesh other women may have had subclinical infection and it is likely that clinically evident infection may be an important factor particularly as most of these cases were recognised in the early post-operative period. Although all women received peri-operative antibiotic prophlyaxis not all women were treated with pre-operative topical HRT. Post-operative antibiotic administration may have been for an insufficient period of time. In addition, the routine use of post-operative laxatives and a bulking agent in this cohort to avoid defecatory straining may have increased the risk of faecal contamination of the posterior vaginal wall incision. The type of operative repair and suture material employed may also be contributing factors. Iliococcygeus or sacrospinous fixation may cause tension across the vaginal incision predisposing to extrusion of the graft, which may be increased by bilateral fixation. In this study, 1 in 5 women developed vaginal erosion where PFR alone was re-inforced with a polypropylene graft compared to almost 1 in 2 where this procedure was combined with BIF. It is of interest that in almost all of the cases in the latter group, the site of erosion was below the apex midway between the points of iliococcygeus fixation where the repair was under greatest tension. In some of these cases a clear ‘bow string’ was palpable. There were insufficient numbers of women who underwent PFR with mesh without fixation to determine the significance of this factor. The surgical approach to mesh erosion depends upon the degree of erosion. Excision of mesh must depend upon a balance between the risk of recurrence of erosion if too little is removed and the risk of prolapse recurrence if too much is removed. In our experience recurrent mesh erosion is more likely to re-occur in patients in whom the excision was limited and vaginal closure performed in a single layer. Based on our experience, we would recommend a more aggressive surgical approach to primary excision of the eroded material. Although only short-term follow-up is available for this series, there have been no cases of recurrent posterior compartment prolapse in women where more than 50% of the graft was excised. Although the numbers of cases in this series, are small the findings are important and have altered our surgical practice. In women undergoing BIF with graft re-inforcement we no longer place the BIF sutures through the graft and the vaginal mucosa. The BIF sutures are placed more laterally through the vaginal mucosa to reduce tension when secured across the posterior vaginal wall incision. To further reduce the risk of apical erosion, the mesh is anchored at its lateral, cephalad, and caudal limits taking care to fashion the mesh to the exact limits of the space so that the graft is not under tension. Concluding message Mesh erosion is common following vaginal surgery for recurrent posterior wall prolapse employing a synthetic graft with prespinous fixation. Management of this complication may be problematic and re-inforcement with autologous/allograft or xenograft prostheses should be considered as an alternative to synthetic grafts in future.


25 Maher C1, Qatawneh A2, Baessler K 1, Cropper M 3, Schluter P4

1. Mater & Royal Women's Urogynaecology, 2. Mater and Royal Women's, 3. Royal Women's Urogynaecology, 4. University QLD LAPAROSCOPIC COLPOSUSPENSION OR TENSION-FREE VAGINAL TAPE FOR RECURRENT STRESS URINARY INCONTINENCE AND/OR INTRINSIC SPHINCTER DEFICIENCY - A RANDOMISED CONTROLLED TRIAL Hypothesis / aims of study Over the past decade there has been a significant shift towards less invasive continence surgeries including the Tension-free Vaginal Tape (TVT) and laparoscopic colposuspension (LC). The outcomes of these surgeries in high-risk incontinence groups including recurrent stress urinary incontinence and Intrinsic Sphincter Deficiency (ISD) remain unproven. The aim of the paper is to compare the LC and TVT in women with recurrent stress urinary incontinence (previous retropubic surgery) and/or ISD. Study design, materials and methods Between 2001 and 2002, 82 women with recurrent SUI and/or ISD (MUCP≤ 20cmH20) were randomly allocated to the laparoscopic colposuspension (42) or TVT (40). A computer generated randomisation list was held by the non-surgical coauthor. Lists were stratified for ISD and concomitant prolapse surgery to ensure equal distribution. Women presenting primarily with pelvic organ prolapse, rigid urethra and those unfit for general anaesthesia were excluded. Prior to enrolment, all women completed standardised pelvic floor proforma, including vaginal staging using the Pelvic Organ Prolapse Quantification (POP-Q), multichannel subtracted urodynamics, transperineal ultrasound to record bladder neck mobility, Short Urinary Distress Inventory (SUDI), short Incontinence Impact Questionnaire (SIIQ) and SF-36 Health Survey (SF-36). Postoperative reviews were conducted by the non-surgical co-authors at 6 weeks, 6 months and at 6 monthly intervals. At 6 months the complete pre-operative evaluation was repeated. All women were treated on an intention to treat basis and the study conducted according to Consort guidelines. Using a significance level of 5%, the study had an 80% power to detect a difference in success rates previously reported (1) between the groups in women with primary SUI. Results No eligible women refused participation in the trial and 1 failed to complete meaningful review. Preoperative details including age, parity, BMI, smoking, menopausal status, previous hysterectomy, previous continence or prolapse surgery, bladder overactivity, voiding dysfunction, MUCP, pelvic organ prolapse, dyspareunia and scores on quality of life and validated pelvic floor questionnaires were similar between the groups except women in the LC group were significantly older and women in the TVT group had a higher SIIQ score. In the LC group 65% and in the TVT group 61% had recurrent SUI (p= 1.00).Table 1 reports important perioperative details and outcomes. On logistic regression analysis no single factor was independently associated with outcome. In the LC arm 9 women underwent open procedures due to BMI ≥ 35. In the TVT group one woman had her procedure converted to open colposuspension due to inability to traverse retropubic space without bladder perforation and 1 had an incidental grade 1 transitional cell carcinoma of the bladder identified. Complications and re-operation rates were similar in each group.

Lap. colposuspension TVT n X (%) N x (%) P Subjective success rate 42 34 (81) 40 35 (85) 0.77 Objective success rate 40 31 (78) 40 34 (85) 0.56 De novo OAB 40 4 (10) 0 0 (0) 0.09 De novo voiding dysfunction 40 2 (5) 0 0 (0) 0.43 Aware of prolapse 42 3 (7) 40 2 (5) 1.00 Sexually active 41 18 (44) 40 21 (53) 0.51 Dyspareunia 18 1 (6) 21 3 (14) 0.61 Concomitant prolapse surgery 42 7 (17) 40 6 (15) 0.77 n mean SD N mean SD P Operating time (mins) 42 44 17 40 30 16 <0.001 Blood loss (mls) 42 105 79 40 96.9 92 0.2 Days in hospital 42 3.4 1.2 40 2.4 1.2 <0.001* Catheter days 4.1 2.7 2.6 40 1.4 2.1 <0.001*


Return normal activity (day) 29 25.0 9.7 33 17.9 9.7 0.002* Review length (months) 42 19.1 10.1 39 18.0 8.4 0.79* Cost Aus $ 42 3,388 718 40 3,633 684 0.11 Patient Satisfaction (0-10) 42 9.0 1.1 40 8.6 1.9 0.45 Postop. increase MUCP 37 7.9 25 38 4.6 19.6 0.69* Change in SUDI 41 40 31 40 43 25 0.97* Change in SIIQ 41 48 39 40 62 32 0.85* Change SF-36 25 4.0 11.9 31 4.3 9.8 0.37*

Table 1. Perioperative details and outcomes

P-values calculated using Fishers exact test unless specified otherwise. * Wilcoxon’s two-sample test

Interpretation of results In the medium term the LC and TVT are equally effective in women with recurrent SUI and or ISD. The TVT is associated with a statistically significant reduced operating time, catheter days, inpatient days and a quicker return to activities of daily living. Concluding message The LC and TVT are equally effective in women with recurrent SUI and or ISD. References 1. Neurourol Urodyn 2003;22(5): 487-8. FUNDING: Scholarship Johnson &Johnson Australia 26 Foote A1, Carne C1, Lowndes C1

1. Calvary Hospital LAPAROSCOPIC COLPOSUSPENSION VS VAGINAL MESH SLING: A RANDOMISED PROSPECTIVE TRIAL Hypothesis / aims of study This study aimed to determine which was the most effective form of two minimally invasive surgeries to treat female genuine stress incontinence. In particular laparoscopic colposuspension was compared with vaginal mesh sling (SPARC) in a randomised prospective trial. Mesh sling surgery was first described in 1995. Mesh sling surgery was compared with open colposuspension in 2000 (1), in a randomised trial of 319 women, and found a similar success rate (89 vs 85%) with a significantly reduced hospitilisation rate (2.2 vs 6.5 days). Burch colposuspension was first described in 1960, with a short term success rate of 90% and a 10 year success rate of 70% (2). Laporoscopic colposuspension was first performed in 1991, and has been compared with open Burch colposuspension in 2000 (3) with a randomised trial of 200 women. The success rates were similar (80%) with the laparoscopic group having a quicker recovery Study design, materials and methods Over a 2 year period, from January 2002 to March 2004, 80 women with urodynamically proven genuine stress incontinence were randomised to either laparoscopic colposuspension (LC) or vaginal mesh sling (VMS). The trial was approved by an ethics committee. Patients were excluded from the study if they had other bladder diagnoses such as detrusor instability or voiding difficulty, previous retropubic surgery, weight over 100kg, significant prolapse, required other gynaecological surgery, or were unsuitable for laparoscopic surgery. All surgeries were performed by the author. Baseline assessment included urodynamics, bladder diary, VAS score, Quality of Life Questionnaires (York and Urogenital Distress Inventory). Patients were again assessed at 6 months. Statistical analysis was performed using student T test and Chi squares with signifiance reported if P<0.05. At baseline there were no significant different differences between the two groups. LC (n=40) VMS (n=40) P Age 51.3 54.9 NS Weight 70.0 73.1 NS Parity 2.7 2.5 NS


Results The VMS group had significantly shorter surgery time, hospitilisation and recovery. LC (n=20) VMS (n=23) P Surgery (min) 48.6 31.3 <0.0001 EBL (mls) 102 83 0.04 Hospital (days) 4.1 1.6 <0.0001 Recovery (weeks) 3.8 2.8 0.01 Intraoperative complications in the laparoscopic group were one bladder suture requiring intraoperative repositioning. The vaginal prolene sling group had 3 needle perfotrations of the bladder requiring intraoperative repositioning. At six months the two groups had a similar success rate (90% vs 87%), with similar results also seen in VAS, and QOL assessments. There was a trend towards increased urgency in the VMS group. LC (n=40) VMS (n=40) P Leaks/wk 0 8.55 8.89

6 1.35 3.1 NS York 0 97.61 97.11 6 99.65 99.62 NS UD 0 80.3 80.4

6 94.7 97.7 NS VAS 0 5.5 5.0 6 1.5 0.6 NS Cured/improved 18/20 (90%) 20/23 (87%) NS Voiding difficulty 0 1 Urgency 3 6 UTIs 0 1 Mesh erosion 0 1 Prolapse 1 0 Concluding message In the short term VMS results in significantly shorter operating time, time in hospital, and time to normal duties. In the longer term there were no significant differences between the two groups although the VMS had a higher incidence of urgency and a vaginal mesh erosion was noted. Laparoscopic colposuspension may be indicated for younger women who do not need prolapse surgery and in whom a long term foreign body may be of concern with regards to urgency and erosion. References 1. A randomised trial of colposuspension and tension-free vaginnal tape (TVT) for primary stress incontinence. Neuro Urol 2000;19(4):386-388 2 Burch colposuspension: a 10-20 year follow up. Br J Obstet Gynaecol 1995;102:740-5 3. Laparoscopic versus open colposuspension: a prospective multicentre randomised single-blind comparison. Neuro Urol 2000;19(4):389-390 27 De Ridder D1, Claerhout F2, Verleyen P1, Boulanger S 1, Deprest J 21. Urology, University Hospitals KU Leuven, 2. Gynecology, University Hospitals KU Leuven PORCINE DERMIS XENOGRAFT AS REINFORCEMENT FOR CYSTOCOELE STAGE III REPAIR: A PROSPECTIVE RANDOMIZED CONTROLLED TRIAL Hypothesis / aims of study Vaginal cystocoele repair using native tissues results in a high recurrence rate. Synthetic implant materials such as Marlex or prolene meshes have shown to reduce the cystocoele recurrence rate. Biomaterials have been used as well, but only short term data are available. To evaluate the eventual advantages of biomaterials in this indication we designed a prospective randomised controlled trial comparing porcine dermis ( Pelvicol ® ) with polyglactin mesch (Vycril ® ). The medium term results are presented (mean follow up 25 months) Study design, materials and methods Patients with a stage III cystocoele were enrolled after informed consent.The surgical procedure ( Raz 4 defect repair) was standardized and performed by three surgeons. Patients were randomised in two groups.


In group I the cystocoele reduction was done by a plug of porcine dermis (Pelvicol) and the reapproximation of the perivesical fascia was reinforced with a porcine dermis overlay. In group II the same procedure was done with the use of a polyglactin mesh (Vycril). The pre operative assessment consisted of clinical examination with POP score, video urodynamic evaluation and two questionnaires ( UDI-6 and IIQ-7). Primary outcome measure was clinical cystocoele recurrence defined as cystocoele stage II. Secondary measures were secondary prolaps, changes in UDI-6 and IIQ-7, complications and secondary surgery. Post-operative evaluation consisted of clinical examination with POP measurement and evaluation of questionnaires and registration of complications, adverse events and eventual subsequent surgery. This was done at 3, 6, 12, 18 and 24 months. Results: In total 134 women were included between jan 2001 and December 2003. The mean follow up for group I (n=65) was 24,8 ± 5,3 months and for group II (n=69) 25,9 ± 6.4. The mean age was 70.09 (range 24-86) for group I and 69.47 ( 36-83) for group II. Both groups were matched. In group I 38 patients underwent a concomitant vaginal hysterectomy, 10 had a rectocoele repair and 17 had no concomitant surgery. In group II 41 had a vaginal hysterectomy, 13 had a rectocoele repair. The cumulative recurrence rate at 24 months in group I was 6 on 63 evaluable patients ( 9.5%) and 19 on 62 (30,6%). T-test p value 0.002.

02468

101214161820

3m 6m 12m 18m 24m

pelvicol

control

Secondary repair of the recurred cystocoele was done in 3 patients in group I (4.7%) and in 9 (14.5%) in group II. There were no differences in peri-operative complication rate, nor in secondary prolapse rates of the mid or posterior compartments. UDI-6 and IIQ-7 showed an advantage for group I, without reaching statistical significance. Interpretation of results The use of porcine dermis ( Pelvicol ® ) results in a significant decrease of cystocoele recurrence in stage III cystocoele repair using the Raz 4-defect repair at 2 years follow up, compared to polyglactin mesh. It did not show any increase in complication rate. Concluding message Porcine dermis ( Pelvicol ® ) is useful and safe as reinforcing material in high grade cystocoele repair. 28 Guerette N1, Davila G W1

1. Cleveland Clinic Florida CAN DISCRETE VAGINAL FASCIAL DEFECTS BE ACCURATELY IDENTIFIED PRE-OPERATIVELY? Hypothesis / aims of study To evaluate the pre-operative predictability of discrete defects in the endopelvic fascia and characterize commonly found defects.


Study design, materials and methods This was a prospective, blinded case-series including 82 consecutive women undergoing vaginal reconstructive pelvic surgery from October of 2002 to January of 2004. Pre-operative examination included careful evaluation for the presence and location of discrete fascial defects by an experienced examiner (examiner #1). The presence and location of fascial defects were then recorded intra-operatively by a different experienced examiner (examiner #2) after the vaginal mucosa was dissected off the endopelvic fascia. Examiner #2 was blinded to the predicted defects noted in the pre-operative examination by examiner #1. The results of the pre-operative and intra-operative exam were then compared. Site-specific repairs were performed on all fascial defects. Results The average age of the women enrolled in the study was 63.7 (43-88) years. The pre-operative predicted defects and intra-operative findings were as follows:

Defect Type Predicted (%) Intra-op (%) Defect Type Description PST 63 (76.8%) 59 (72.0%) Posterior superior transverse separation from vaginal apexAST 14 (17.1%) 9 (11.0%) Anterior superior transverse separation from vaginal apex NONE 11 (13.4%) 12 (14.6%) No fascial defect identified AC 2 (2.4%) 0 Anterior central defect PC 1 (1.2%) 3 (3.6%) Posterior central defect PSR 0 4 (4.9%) Posterior superior right-sided separation PIT 0 1 (1.2%) Posterior inferior transverse separation from perineal body

The pre-operative exam accurately predicted specific intra-operative findings in 55 (67.1%) of the cases. Interpretation of results The most common defect predicted (76.8%) and encountered intra-operatively (72%) was a transverse separation of the posterior endopelvic fascia from the vaginal apex. The second most frequently predicted (17.1%) and intra-operatively encountered (11.0%) defect was an anterior transverse separation of the endopelvic fascia from the vaginal apex. The remainder of the defect types, including separations of the recto-vaginal septum from the perineal body (1.2%), were relatively uncommon. Fascial breaks of any sort were present in 85.4% of the patients. Concluding message Specific defects in the endopelvic fascia are extremely common in association with vaginal prolapse. These are usually separations of the endopelvic fascia from the apex, particularly in the posterior vagina. However, the ability to accurately determine the presence and location of a specific defect on pre-operative examination is limited. 29 Abramov Y1, Gandhi S1, Goldberg R 1, Botros S1, Kwon C2, Sherman W1, Sand P1

1. Evanston Continence Center, Northwestern University, Feinberg School of Medicine, 2. Division of Urogynecology, New York University School of Medicine DOES DISCRETE SITE-SPECIFIC DEFECT REPAIR CARRY BETTER OBJECTIVE AND SUBJECTIVE OUTCOMES THAN STANDARD POSTERIOR COLPORRHAPHY? Hypothesis / aims of study Previous reports have advocated discrete site-specific defect repair of Denonvillier’s fascia for correction of advanced rectocele, with favorable anatomic outcome as well as sexual and bowel function (1, 2). In this study, we assessed objective and subjective outcomes of this technique one year postoperatively, as compared to standard posterior colporrhaphy with midline plication.


Study design, materials and methods Office and hospital charts of all 307 patients who had repair of advanced rectocele in our institution between July 1998 and June 2002 were systematically reviewed. During this time period, all patients undergoing posterior vaginal repair were evaluated intraoperatively for discrete defects in the Denonvillier’s fascia. Whenever found, these defects were repaired in a site-specific manner, as previously described (1, 2). Standard posterior colporrhaphy with midline plication of the endopelvic connective tissues was performed in all cases with midline defects or diffuse weakness of the fascia, or when an isolated defect could not be found. For each patient, we recorded preoperative and one year postoperative pelvic exams by the Baden-Walker and POP-Q techniques. Dyspareunia and bowel symptoms were assessed with Likert scales before and one year after surgery. Data were analyzed using the student t-test, Chi-square test, and a multivariate logistic regression model. Results Table 1: Objective and subjective outcomes of discrete site specific defect repair vs. standard posterior colporrhaphy Variable Site specific repair Standard colporrhaphy P (n=124) (n=183) Recurrence rates 2nd degree† 41(33) 26(14) 0.001* ≥ 3rd degree† 14(11) 7(4) 0.02* Mean postop Bp point‡ (cm) -2.2 -2.7 0.001* Subjective recurrence (11) 7(4) 0.02* Dyspareunia Preoperative 9(7) 13(7) 1.00 Postoperative 24(19) 26(14) 0.30 Constipation Preoperative 41(33) 55(30) 0.68 Postoperative 50(40) 53(29) 0.20 Diarrhea Preoperative 17(14) 18(10) 0.42 Postoperative 19(15) 17(9) 0.19 Abdominal pain Preoperative 30(24) 38(21) 0.63 Postoperative 14(11) 18(10) 0.68 Fecal Incontinence Preoperative 19(15) 37(20) 0.31 Postoperative 24(19) 28(15) 0.49 Flatal Incontinence Preoperative 73(59) 90(49) 0.53 Postoperative 58(47) 79(43) 0.47 * Statistically significant; †According to the Baden-Walker halfway system; ‡According to the POP-Q system. Values are presented as number (%) unless indicated otherwise. Interpretation of results 124 patients underwent site-specific defect repair (81% combined, 13% distal, and 7% proximal defects) and 183 patients underwent standard posterior colporrhaphy. One year postoperatively, recurrence rates of rectocele both beyond the midvaginal plane, and beyond the introitus, as well as mean postoperative Bp point were significantly higher in the site-specific repair group (Table 1). In addition, prevalence of symptomatic bulge was more prevalent among the site-specific group. Both groups did not differ in mean age (73 vs. 72 yrs), parity (2.67 vs. 2.84), BMI (26.5 vs. 26.1), preoperative prolapse (2nd degree: 58% vs. 57%; 3rd degree: 26% vs. 28%; 4th degree: 16% vs. 15%), preoperative mean Bp point values (-0.4 vs. -0.3cm), concomitant surgical procedures (hysterectomy: 34% vs. 30%; anterior colporrhaphy: 91% vs. 90%; incontinence procedure: 81% vs. 80% and vaginal vault suspension: 29% vs. 27%), intraoperative bleeding (298cc vs. 314cc) and perioperative complication rates (hemorrhage: 4 vs. 5 patients; wound infection: 3 vs. 2 patient; and medical complications: 4 vs. 3 patients). Overall dyspareunia rates were significantly higher postoperatively than preoperatively (16% vs. 7%, p = 0.001). Pre- and postoperative rates of dyspareunia were not significantly different between the site-specific and posterior colporrhaphy groups. Overall rates of


constipation (31% vs. 35%), diarrhea (12% vs. 10%), abdominal pain (22% vs. 17%), fecal incontinence (18% vs. 15%), and flatal incontinence (53% vs. 46%), were not significantly different pre- and postoperatively. Pre- and postoperative rates of these symptoms were not significantly different between the site-specific and posterior colporrhaphy groups. Concluding message Discrete site-specific defect repair of Denonvillier’s fascia is associated with significantly higher objective and subjective recurrence rates as compared to the standard posterior colporrhaphy at one year of follow-up. Overall rates of dyspareunia increase following rectocele repair while bowel dysfunction rates do not significantly change irrespective of the surgical technique used. Site-specific defect repair is not superior to standard posterior colporrhaphy with regard to long-term postoperative dyspareunia or bowel dysfunction. These techniques should be further evaluated using randomized controlled trials. References 1. An anatomic and functional assessment of the discrete defect rectocele repair. Am J Obstet Gynecol 1998; 179:1451-6. 2. The anatomic and functional outcomes of defect-specific rectocele repairs. Am J Obstet Gyencol 1999; 181: 1353-8. 30 Kim J1, Kim T1, Lim K1, Joo K1

1. Samsung Cheil Hospital & Women's Healthcare Center, Sungkyunkwan Univ School of Med HYSTERECTOMY; IS IT ESSENTIAL FOR THE CORRECTION OF UTERINE PROLAPSE? Hypothesis / aims of study Vaginal hysterectomy is considered the treatment of choice for uterine prolapse, despite a dropped uterus is the result and not the cause of genital prolapse. The aim of this study is to compare the efficacy of transvaginal sacrospinous cervicocolpopexy without hysterectomy and with hysterectomy for the correction of symptomatic uterine prolapse. Study design, materials and methods A retrospective chart review was performed to identify women who underwent sacrospinous ligament suspension in our institution between 1998 and 2002. 155 women with a symptomatic uterine prolapse were treated with either transvaginal sacrospinous cervicocolpopexy without hysterectomy and anterior-posterior colporrhaphy (83 cases =Group A) or transvaginal sacrospinous ligament colpopexy with hysterectomy and anterior –posterior colporrhaphy( 72 cases =Group B). Patients were reviewed at least 12 months after operation. Preoperative patient characteristics, operative and postoperative events and follow-up results were recorded. Results The mean age, parity, prolapse grade, body weight, menopausal status and length of follow-up for two groups were no difference. There were 4 intraoperative complications - One rectal wall injury and one bladder laceration in group A and two rectal wall injuries in group B. There were no acute hemorrhage and no deaths. The mean duration of surgery, hemoglobin change, catheter days and inpatient days were shorter in group A compared with group B. (Group A 102.5±33.4(min), 2.4±0.7(mg/dL), 5.2±1.4(day), 7.6±2.2(day) vs Group B 135.3±33.9, 2.9±0.8, 6.1±2.1, 9.4±3.7) Recurrent cystocele developed in 6(7.2%) patients in group A and 4(5.6%) in group B. 6 patient (7.2%) in group A and 5 patient (6.9%) in group B required repeat operation for recurrent pelvic organ prolapse. There was no significant difference between the two groups in postoperative satisfactory result. (92.8% vs 93.1%, respectively p=0.8) Interpretation of results Transvaginal cervicocolpopexy without hysterectomy and sacrospinous colpopexy with hysterectomy are equally effective surgical operation for uterine prolapse Cervicocolpopexy avoids the potential morbidity of hysterectomy and decreases the operation time, blood loss, catheter days and inpatient days.


Concluding message This study shows that hysterectomy is not essential for the correction of uterine prolapse. Table 1 Demographics and clinical characteristics

Demographic With hysterectomy(n=83) Without hysterectomy(n=72) P value Age(y) 60.1±10.4 58.6±8.5 NS Parity(n) 4.3±1.9 4.2±1.8 NS Weight(kg) 58.3±7.5 59.3±7.6 NS Menopause(n) 68(81.9%) 62(86.1%) NS Uterine prolapse 2.6±0.9 2.8±0.8 NS

Cystocele 2.8±0.8 2.6±1.1 NS Rectocele 2.0±1.1 2.2±1.2 NS Length follow-up(months) 12.8±15.9 15.9±18.3 NS

Data are given as Mean ±SD Table 2 Perioperative details

Detail With hysterectomy(n=83) Without hysterectomy(n=72) P value Operative time(min) 102.5±33.4 135.3±33.9 < 0.05 Hemoglobin change(mg/dL) 2.4±0.7 2.9±0.8 < 0.05 Catheter days 5.2±1.4 6.1±2.1 < 0.05 Inpatient days 7.6±2.2 9.4±3.7 < 0.05

Data are given as Mean ±SD Table 3 Recurrent uterine or pelvic organ prolapse

Recurrence(n) Requiring Reoperation(n) Leading part of recurrence Group A (n=83) Group B (n=72) Group A(n=83) Group B(n=72) Cervix/vault 5(6.0%) 4(5.6%) 4(4.8%) 3(4.2%) Cystocele 6(7.2%) 4(5.6%) 2(2.4%) 2(2.7%) Rectocele 1(1.2%) 1(1.4%) 0 0 Total 12(14.5%) 9(12.5%) 6(7.2%) 5(6.9%)

31 Dietz H P1, Eldridge A 2, Grace M2, Clarke B3

1. RPAH Sydney, 2. QIMR Brisbane, 3. RWH Brisbane THE PREVALENCE OF RECTOVAGINAL FASCIAL DEFECTS IN YOUNG NULLIPARAE: CAN RECTOCELE BE A CONGENITAL CONDITION? Hypothesis / aims of study A true rectocele, i.e., a defect in the rectovaginal septum or Denonvillier’s fascia, is traditionally regarded as the archetypal traumatic pelvic floor lesion (1). It is generally assumed that such fascial defects are the result of childbirth, and rectoceles in nulliparous women are attributed to longstanding abnormal defaecation habits (2). If those assumptions were correct, one would not expect to find defects of the rectovaginal septum in young women prior to childbirth. This study defines the incidence of true rectocele in a cohort of 178 young nulliparous women. Study design, materials and methods We report an observational cohort study on 178 young nulliparous Caucasian women (age 18-25), recruited through the Australian Twin Registry for a twin study of pelvic floor anatomy and function. All women were interviewed and then examined by translabial ultrasound, supine and after bladder emptying (3). In a minority of 52 women 3D imaging was obtained, and most other scans were recorded on VHS video for quality control. All scans were performed by the principal investigator or by staff trained by him for a minimum of 100 assessments. Printouts, video recordings and volume ultrasound data were all reviewed by an assessor blinded against interview and demographic data for an evaluation of rectovaginal septum integrity. Ethics Committee approval had been obtained for the main study (QIMR P434 (H0202-01-004)), and all subjects gave written informed consent. They received a shopping voucher over A$ 100.- for their participation.


Figure: Small rectocele in 21 year old nulligravid Caucasian female. Image on left is at rest, image on right is at maximal Valsalva. Results 171 women had a technically adequate scan. In seven cases the posterior compartment could not be assessed fully. This was mostly due to faulty transducer alignment. A discontinuity of the anterior rectal wall with extrusion of rectal mucosa or contents (depth of 10 mm or more) was observed in 21/ 171 (12%). The depth of this herniation ranged from 10 to 25 mm and was filled with stool on 10 occasions, with rectal mucosa in 11 cases. None of the 171 women showed an enterocele. Descent of the rectal ampulla or anorectal junction to beyond the level of the symphysis pubis without actual fascial defect, i.e., significant perineal relaxation, was observed in 23/171 (13%) of the study population. The finding of a rectovaginal septal defect was weakly associated with a higher Body Mass Index (p= 0.049) and with the complaint of chronic constipation (p= 0.049), and there was a weak trend towards an association with frequent straining at stool (p= 0.1). There also was an association with higher anterior compartment descent (p= 0.01). Neither a history of indicators of connective tissue abnormality (such as dislocations, epistaxis or herniae), a family history of prolapse or prolapse surgery, nor a clinical assessment of upper extremity joint mobility were associated with defects. Interpretation of results In this study of 171 nulligravid Caucasian women aged 18- 25, defects of the rectovaginal septum were demonstrated in 12% of subjects. As all confounding factors (most importantly levator coactivation which is common in nulliparous women) would tend towards minimisation of pelvic organ descent and rectocele development, this is likely to be an underestimate. Associations were observed with higher body mass index and a history of constipation which suggests that in some young women with bowel dysfunction such defects may be acquired in childhood and/ or early adulthood. Another explanation may be that, at least in some women, the observed defects are in fact congenital in nature. Concluding message Defects of the rectovaginal septum can be visualized on translabial ultrasound and are found in a surprising number of nulligravid young women, raising the possibility of a congenital aetiology. References 1 Contemporary reviews in Obstetrics and Gynecology 1997;303-310. 2 Curr Opin Obstet Gynecol 1996; (8): 876-879 3 Ultrasound in Obstetrics & Gynecology 2001; (18): 511-514.


32 Faltin D1, Otero M1, Floris L1, Sangalli M2, Bianchi-Demicheli F1, Vieille J1, Weil A1, Irion O1, Boulvain M1 1. University Hospitals of Geneva, 2. Women's health service, Wellington Hosp WOMEN'S HEALTH 18 YEARS AFTER RUPTURE OF THE ANAL SPHINCTER DURING CHILDBIRTH. Hypothesis / aims of study Maternal anal sphincter tears during childbirth are associated with subsequent fecal incontinence despite primary repair. The long-term impact of this complication of vaginal delivery is not well known. Study design, materials and methods From the 4569 women who delivered in 1982 and 1983 in our hospital we selected the 445 women (9.7%) having sustained an anal sphincter tear during childbirth and 445 control women who were group-matched for parity. Eighteen years later we contacted them and send a postal questionnaire assessing general health, urinary and faecal incontinence, and sexual satisfaction. The main outcome measure was faecal incontinence graded by the Wexner score, which measures incontinence to flatus, liquid or solid stools, need to wear a pad, and lifestyle alterations. Results We were able to locate 701/890 (78.8%) of the women who were on average 46.6 (SD 4.6) years old, and 549/890 (61.7%) returned the questionnaire. Faecal incontinence symptoms (mostly occasional involuntary passage of flatus) were reported by 132/259 (51.0%) women with a sphincter tear and 113/281 (40.2%) controls (risk difference 10.8%, 95% confidence interval 2.4% to 19.11%, P=0.01) . Severe faecal incontinence (Wexner score above 4) was reported by 34/259 (13.1%) women after a sphincter tear and 22/281 (7.8%) controls (risk ratio 1.68, 95% confidence interval 1.01 to 2.79, P=0.04). After a sphincter tear, women had poorer scores in specific quality of life domains affected by faecal incontinence (P=0.02). Moreover, the mental component of the generic short-form-12 health survey showed lower scores among women with a previous sphincter tear (P=0.05). The prevalence of urinary incontinence and sexual satisfaction were similar in women with and without a previous sphincter tear. Only 68/252 (26.9%) women knew they had sustained an anal sphincter tear. The proportion of faecal incontinence attributable to an anal sphincter tear in this population was only 3.9%. Interpretation of results Anal sphincter tears during childbirth are associated with long-term faecal incontinence. Although most women experience minor symptoms, their quality of life is affected and their mental well-being might be affected. Paradoxically, only a minority of women with faecal incontinence have a history of sphincter tear. Concluding message Interventions to prevent, diagnose and treat faecal incontinence, a significant maternal morbidity 18 years after delivery, should be promoted. FUNDING: Swiss National Science Foundation, grants 32-55907.98 and 3200-064056.00 33 Andrews V1, Thakar R1, Sultan A1

1. Mayday University Hospital OCCULT ANAL SPHINCTER INJURIES -- MYTH OR REALITY? Hypothesis / aims of study Anal incontinence is a social stigma and because of embarrassment is frequently underreported. A major contributory factor is obstetric trauma with may be either recognised or occult(1). Recognised anal sphincter injuries occur in 0.5 to 19% depending on whether a mediolateral or midline episiotomies is practised. Occult


anal sphincter injuries diagnosed by anal endosonography at six to twelve weeks postpartum have been reported in 20 – 41% of primiparous women. However it remains to be established whether these “occult” injuries are truly occult or are missed at the time of delivery. The aim of this study was to establish the true prevalence of recognised and occult anal sphincter injury at the time of the first vaginal delivery. Study design, materials and methods In this prospective study consenting women having their first vaginal delivery had an endoanal ultrasound performed immediately after delivery and at six to twelve weeks postpartum. In addition all women had a perineal and rectal examination at delivery by an experienced clinical research fellow. Any discrepancies on clinical examination were verified by the on call consultant or registrar. The endoanal ultrasound scans were recorded on videos and reported by an expert who was blinded to the study. Results 254 women having their first vaginal delivery were invited of whom 241 (95%) agreed (8 had a previous caesarean section). Of the 241 women 11 (4.6%) had a forceps delivery, 14 (16.6%) a ventouse delivery and 12(5%) had a combined ventouse and forceps delivery. Mean birthweight 3.4kg (+/- 0.49 SD). 209 (87%) returned for follow up at six to twelve weeks. There were 11 discrepancies on scan reports that were resolved on review. There were three defects on endoanal ultrasound that were not clinically apparent. All three defects persisted at follow up. Two defects only involved the internal sphincter, and one was a combined sphincter defect. The anal endosonographic findings immediately before repair and 6 to 12 weeks postpartum are outlined in Table 1.

Table 1. Anal endosonography findings in relation to degree of tear Type of injury Number of cases

(%) n=241

Number with defect on anal endosonography immediately prior to perineal repair (%) n =241

Number with defect on anal endosonography 6 -12 weeks post partum (%) n=209

Intact perineum 29 (12)

1/29 (3.4) 1/24 (4.2)

First degree tear 17 (7.1)

0/17 (0) 0/16 (0)

Second degree tear 136 (56)

2/136 (1.5) 2/111 (1.8)

3a tear (<50% external anal sphincter disrupted)

28 (11.6) 28/28 (100) 0/27 (0)

3b tear (>50% exeternal anal sphincter disrupted)

30 (12.4) 30/30 (100) 6/30 (20)

3c tear (internal anal sphincter involved)

0 0/0 (0) 0/0 (0)

Fourth degree tear (involving the anal mucosa)

1 (0.5) 1 (100) 0/1 (0)

All third/fourth degree tears 59 (24.5) 59/59 (100) 6/58 (10) Interpretation of results The true prevalence of recognisable anal sphincter injuries is much higher than previously reported. All clinically recognisable injuries at delivery were demonstrable by anal endosonography. Three defects were not clinically recognised at delivery. Two of these were isolated internal sphincter defects that would not normally be apparent clinically. The remaining undiagnosed combined defect may have been missed clinically or be truly occult. No women developed a de novo sonographic defect at follow up. Concluding message The prevalence of clinically recognisable anal sphincter injury was much higher than previously reported and all injuries were confirmed by postpartum anal endosonography. The prevalence of true occult anal sphincter defects was negligible and no de novo anal sphincter defects were identified. This study demonstrates that


the previously reported high prevalence of occult anal sphincter injuries (1) were actually missed rather than truly occult. Therefore with better training the clinical diagnosis of anal sphincter injury can be dramatically improved and thereby minimise the morbidity associated with childbirth. Reference 1. Anal sphincter disruption during vaginal delivery. New Eng J Med 1993; 329: 1905-1911. 34 Balmforth J1, Gladman M2, Cardozo L1, Williams N2

1. Kings College Hospital, 2. Barts and The London WOMEN WITH RECTAL OUTLET OBSTRUCTION HAVE ALTERED BLADDER FUNCTION Hypothesis / aims of study Previous urodynamic studies of women with constipation have demonstrated conflicting results, possibly on account of the inclusion of heterogenous patients in terms of severity and underlying pathophysiology of their constipation. Advances in anorectal physiological investigation allow constipated patients to be divided into those with colonic dysmotility and / or outlet obstruction, the latter being characterised by incomplete rectal evacuation and chronic retention of faeces. Although acute rectal distension influences voiding function and bladder sensation in a laboratory setting [1], the effect of chronic rectal distension is unknown. This study aimed to investigate bladder function in a homogenous group of constipated women with outlet obstruction confirmed on physiological investigation. Study design, materials and methods Women were recruited prospectively over a two year period, from those referred to a tertiary centre for investigation of intractable constipation refractory to simple dietary / medical measures. The study population comprised 24 women (median age 55, range 29-67 years), included on the basis of having symptoms of obstructed defecation in accordance with Rome II diagnostic criteria for functional bowel disorders [2] and outlet obstruction on evacuation procotography. Local ethics committee approval was obtained prior to commencing the study. All subjects underwent anorectal physiological investigation, including anal manometry, quantification of rectal sensation by volumetric distension and endoanal ultrasound. Colonic transit and rectal evacuatory function were assessed using radio-opaque marker studies and evacuation proctography, respectively. Videourodynamic assessment, consisting of uroflowmetry, measurement of post-void residual, subtracted filling cystometry and pressure-flow studies, was performed in all subjects using a Laborie Aquarius urodynamic system. Urodynamic methods and terminology were performed in accordance with ICS standards. Bladder sensory function was quantified by recording the volumes and detrusor pressures required to elicit first sensation of filling, first desire to void and strong desire to void during filling video cystometry with radio-contrast infused continuously at a rate of 30 ml/min. Filling was stopped at 800ml to avoid overdistension. Data were compared to normal ranges obtained using an identical technique in asymptomatic healthy volunteers of similar age [3]. Results Anorectal physiological investigation revealed delayed colonic transit, in addition to outlet obstruction, in 11/24 patients (46%). Rectal sensory function was normal in 7/24 patients (29%), and abnormal in 17 (71%). Voiding function was normal in 23/24 patients (96%), with only 1 patient having voiding difficulty (PFR<15ml/s and residual >100mls). Six women (25%) had impaired bladder sensation, with elevation of sensory thresholds above the normal range. Bladder sensation was absent in 4/24 women (17%) at 800mls, all of whom had significantly impaired rectal sensation. Comparison of urodynamic parameters between the subgroups of patients with normal and abnormal rectal sensation revealed similar voiding, but significantly different bladder sensory function (Table 1).


abn.

rectal

sens

norm

al ran

ge

norm

. recta

l sen

s

abn.

rectal

sens

norm

. rang

e

norm

. recta

l sen

s

abn.

rectal

sens

norm

al ran

ge

norm

. recta

l sen

s0

100

200

300

400

500

600

700

800

first fillingsensation

first voiding desire

strong voiding desire

scatterplot showing distribution and mean bladder sensorythresholds in women with normal and abnormal rectal sensation

volu

me

at s

enso

ry th

resh

old

(ml)

normal rectal sensation n=7

abnormal rectal sensation n=17 Urodynamic Parameter

Mean SD Mean SD

p value (Mann-Whitney)

Peak flow (ml/s) 19.8 20.0 23.4 12.6 0.902 Residual (ml) 11 16 57 148 0.405 1st sensation of filling (ml) 71 65 499 237 <0.001 1st desire to void (ml) 213 98 636 194 <0.001 Strong desire to void (ml) 322 141 688 172 0.001 Pdet rise@max capacity (cmH20) 3.57 2.30 2.19 0.85 0.109 Urodynamic diagnoses 1 detrusor overactivity

1 urodynamic stress incontinence 5 normal

4 Absent sensation 6 impaired sensation 3 urodynamic stress incontinence 1 mixed DO/USI 3 normal

TABLE 1: Urodynamic parameters in women with outlet obstruction according to rectal sensation. The two groups of women had similar mean ages but there was a statistically significant difference in the number of previous abdominal or pelvic operations undergone.

RECTAL SENSATION 1st constant sensation

Desire to defaecate Maximum toleration

BLADDER SENSATION r p r p r p 1st sensation of filling 0.433 0.034 0.425 0.039 0.391 0.059 1st desire to void 0.501 0.012 0.459 0.024 0.438 0.032 Strong desire to void 0.439 0.032 0.363 0.082 0.317 0.131 TABLE 2: Correlation of bladder and rectal sensory thresholds. Correlation analysis revealed significant association between bladder and rectal sensory function at first sensation and desire to void / defaecate.

Interpretation of results In contrast to the effects of acute rectal distension on bladder voiding and sensory function, this study has demonstrated that voiding dysfunction is rare in a homogeneous cohort of women with objective evidence of rectal outlet obstruction. However, a proportion do have evidence of impaired, or absent bladder sensory


function, and this was associated with impairment of rectal sensory function on physiological investigation in all women. Bladder and rectal sensory function appear to be significantly associated except at extremes of filling, which may be explained on account of censoring of data due to cessation of bladder filling at 800ml. Concluding message Chronic rectal evacuatory dysfunction in women with outlet obstruction does not appear to adversely affect voiding function. These data suggest that women with impaired rectal sensation are likely to have a co-existing impairment in bladder sensation, suggestive perhaps of a common aetiological factor. The clinical significance of impaired bladder sensation in this cohort of patients remains unknown, but may provide a pathophysiological mechanism for the development of future bladder dysfunction. The relationship between bladder and rectal sensory function warrants further investigation.

References: 1. Impact of rectal distension on the results of evaluations of lower urinary tract sensation. J Urol. 2003; 169: 1392-1394. 2. Rome II: Functional disorders of the anus and rectum. Gut. 1999; 45: II55-II59. 3. Normality of bladder filing studied in symptom-free middle-aged women. J Urol. 2004; 171: 1567-1570. 35 Hinninghofen H1, Liu M2, Merletti R3, Bottin A3, Enck P4

1. Clinic for General Surgery, Neurogastroenterology, 2. Clinic for General Surgery, University Hospitals Tuebingen, Germany , 3. LISiN Bioengineering Center, Dept. of Electronics, Politecnico di Torino, ITALY., 4. Center for Medical Research, University Hospitals Tuebingen, Germany WITHIN AND ACROSS SUBJECT REPRODUCIBILITY OF THE MULTI-ELECTRODE SURFACE EMG FROM THE EXTERNAL ANAL SPHINCTER. Hypothesis / aims of study Multi-electrode array surface EMG (S-EMG) technique has recently become available for recording and characterization of the electrical properties in the striated muscles in human. Application of this new technique to the external anal sphincter muscle would allow to address the question of its innervation patterns and the electrical properties of this muscle in healthy subjects. This would significantlz enhance our understanding of clinical findings in males and females with disorders of the pelvic floor. Study design, materials and methods A 16-channel multi-electrode array developed for large striated muscles (e.g. the biceps brachii) was arranged around the circumference of a cylindrically shaped probe to perform S-EMG recordings from within the external anal sphincter. (Dimensions of the probe: 14 mm in diameter, carrying an array of 16 silver bars: 1 mm diameter, 10 mm length, 2.75 mm apart). SEMG signals were recorded differentially between adjacent pairs of electrodes during rest and during maximal voluntary contractions (MVC) for 10 sec at each of three levels within the anal canal (1, 2, and 3 cm from the anal orifice). The EMG signals were amplified, sampled at 2048 Hz per channel and stored on a PC after 12 bit A/D conversion. The bandwidth of the EMG amplifier was designed to accommodate the spectrum of the striated muscle EMG. Slow signals produced by active smooth muscles (if any) were rejected by the high pass filter at 10 Hz. Together with a specially designed software, the probe was able to detect the generation point (Innervation zone: IZ), propagation, and extinction of motor unit action potentials (MUAP) produced by individual motor units (MU) of the external anal sphincter muscle. An IZ was defined as the region of a MU generation including the end-plates (or neuromuscular junctions), and its location was defined as the position of the electrode(s) under which the MUAP were generated and began their propagation in opposite directions towards the fiber endings. Criterion for identification of an IZ was if the same MUAP - identified by specific "signature" characteristics (shape, propagation, length) - or different MUAP were generated at the same location more than 30 times during 10 seconds of maximum voluntary contraction. The MUAP detection and extraction were performed with Wavelet techniques, and combined the information provided by the electrode arrays in the spatio-temporal domain. We investigated 15 healthy subjects (6 male : 9 female, 30.5 years) twice within 2 months. The subjects were lying in the left side, and the probe was held in position (channel 1 oriented ventrally) by the investigator. The subject was instructed to relax completely, and to produce three maximum voluntary contractions sustained for 10 sec, at each of three levels within the anal canal (at the anal orifice and 1 and 2 cm proximal). SEMG was recorded also during 10 sec of rest at each level.


Results The software output (Radon Correlation Transform) produced both graphical display as well as a digital reading of the SEMG parameters for each electrode position (or: pair of electrodes) of the probe. The IZ distribution was colour-coded with respect to the number of MUAP detected at each position. MU of the anal sphincter could be detected at different locations along the circumference. Potentials propagated from the IZ towards the fiber endings. With maximum contraction, IZs were detected at each of the three levels within the anal sphincter for every subject. In most cases, only one IZ could be clearly identified, whereas in only a few cases, two or more IZ were recognized the same level. Reproducibility of measurement was good between and within subjects after two months. The computed correlation between both measures was highly significant at level 1 and 3 (r=0.44 and r=0.55, resp. both p<.01), and significant for level 2 (r=0.31, p= <.05). Interpretation of results, Concluding message This multichannel SEMG system is an easy to perform, noninvasive new technique with good reproducibility, that allows to collect important information about the innervation patterns of the external anal sphincter. This will allow reinvestigating the role of innervation in the pathogenesis of fecal incontinence in the future. Funding; grants from the EU – QLRT-2001-00218 – and the Deutsche Forschungsgemeinschaft, EN 50/21). 36 Rizk D1, Mensah-Brown E1, Patel M1, Chandranath S 1, Naseer O1, Ahmed I1, Al-Haj M1, Adem A1 1. Faculty of Medicine and Health Sciences EFFECTS OF OVARIECTOMY AND HORMONE REPLACEMENT ON SUBMUCOSAL COLLAGEN AND BLOOD VESSELS OF THE ANAL CANAL OF RATS. Hypothesis / aims of study The contribution of mucosal or submucosal connective and vascular tissues to anal pressure in women has not been fully appreciated in clinical practice in contrast to their roles in the female urethra [1,2]. Therapeutic success of submucosal anal injection of various bulking agents in women with idiopathic fecal incontinence, however, suggests that a situation analogous to the female urethra might exist in the anal canal [3]. Each of these two connective tissue components, collagen and vascular plexuses, also appear to have some dependence on estrogen and possibly progesterone, as observed in the female urethra [2]. The presence of estrogen and progesterone receptors in the mucosal and submucosal connective tissue of the female anal canal and the ability of these hormones to induce structural changes in individual components such as collagen and blood vessels would provide evidence for an action of female sex hormones on fecal control. Our study attempts to investigate this hypothesis in adult female rats. Study design, materials and methods Experiments were performed on sections of the anal canal (the region extending from the beginning of the anal columns to the orifice) of ovariectomized adult Wistar female rats (weight= 200-250g, age= 5-6 months) following 28 daily subcutaneous injections of 17-ß estradiol 10 µg/kg/day (n=6, OVX + E, Group 1), medroxyprogesterone acetate 0.2 µg/kg/day (n=6, OVX + P, Group 2), both drugs (n=6, OVX +E+P, Group 3) or vehicle (n=6, OVX) and after sham surgery without castration or injection (n=6). Investigations included immunohistochemistry of estrogen and progesterone receptors and collagen fibres, Western blot analysis of collagen types I and III and counting of perianal vessels by light microscopy. The Animal Research Ethics Committee approved the study protocol. Results There was positive immunostaining for estrogen and progesterone receptors in the mucosa and for collagen types I and III in the submucosa in all samples. Western blot analysis showed that collagen type I increased after ovariectomy and then decreased in all groups. Collagen type I levels in sham treated animals were slightly higher than the experimental groups. The greatest decrease was observed in group 1. In contrast, collagen type III levels decreased after ovariectomy. Replacement of estrogen, progesterone and combination of estrogen and progesterone all increased the levels of type III collagen (Figure 1). Semi-quantitative measurement of type I/III collagen ratio, using signal intensity was 3:1 in ovariectomized animal and 1.6:1 in


sham treated rats. Treatment with progesterone (1.3:1) produced a greater effect than either estrogen alone (1:1) or in combination with progesterone (1.2:1) (Figure 1). The differences were however, insignificant. The mean submucosal blood vessel count in the anal canal was significantly increased in sections of ovariectomized rats (14±2.6) compared with sham treated rats (6.2 ± 2.5, p<0.006). The vessel count after estrogen replacement (9.3 ± 1.7) was also significantly greater than that of sham (p= 0.04). The difference between the sham group and progesterone replacement (6 ± 2.9) and a combination of estrogen and progesterone (4.5 ± 1.3) was not significant. Interpretation of results Type I collagen levels increased significantly with ovariectomy but were normalized with treatment with estrogen and progesterone. Type III collagen levels decreased after ovariectomy. Administration of estrogen and progesterone appeared to restore level to near sham values. Type I/III collagen ratios increased markedly after ovariectomy. This appeared to be restored by both estrogen and progesterone administration either individually or in combination. Mean vessel count was significantly lower in sham compared to values in ovariectomized animals. However, while only estrogen treatment increased significantly the number of vessels compared to sham animals, replacement with progesterone did not affect and in combination with estrogen reduced submucosal vessel number.

Figure 1 Western blot analysis of collagen types I and III in the anal submucosa of sham, controls [a] and groups 1 [b], 2 [c] and 3 [d]. Signal intensity for type I increased in controls [a] but decreased in all treatment groups [b,c,d]. Signal intensity for type III decreased in controls [a] but increased in all treatment groups [b,c,d]. Concluding message Estrogen and progesterone have synergistic effects on submucosal collagen types I and III and probably antagonistic effects on the perianal vascular plexus in the anal canal of adult female rats. The present results support for the first time the notion of an effect of both hormones on the submucosal connective and vascular tissues of the female anal canal. These experimental data may have a clinical impact on the management of climacteric women with idiopathic fecal incontinence. References

1. Anorectal anatomy and physiology. Gastroentrol Clin North Am 2001, 30: 1-9. 2. Effects of ovariectomy and hormone replacement on collagen and blood vessels of the urethral submucosa of

rats. Urol Res 2003; 31: 147-51. 3. Glutaraldehyde cross-linked collagen in the treatment of faecal incontinence. Br J Surg 1998; 85: 978-9.

37 Sakakibara R1, Uchiyama T1, Liu Z1, Yamamoto T1, Ito T1, Yamanishi T2, Hattori T1

1. Neurology Department Chiba University, 2. Urology Dokkyo Medical College MOSAPRIDE CITRATE, A NOVEL 5-HT4 AGONIST AND PARTIAL 5-HT3 ANTAGONIST, AMELIORATES CONSTIPATION IN PARKINSONIAN PATIENTS Hypothesis / aims of study Mosapride citrate is a novel 5-HT4 receptor agonist and partial 5-HT3 antagonist [1]. It facilitates acetylcholine release from the enteric cholinergic neurones. In contrast to cisapride, mosapride does not block K+-channels


(cardiac toxicity) or D2 dopaminergic receptors (extrapyramidal dysfunction) [2]. It has been used in delayed gastric emptying due to diabetes [3], gastro-oesophageal reflux disease [4] and functional dyspepsia [5]. Study design, materials and methods We performed an open trial of mosapride citrate (15 mg/day, 3 months) on constipation in our 14 parkinsonian patients (Parkinson’s disease, 7, multiple system atrophy, 7; 10 men, 4 women; mean age, 67 years [55-77]; mean duration of disease, 4 years [1-8]) with objective parameters given by colonic transit time (CTT) and rectoanal videomanometry. Results Mosapride was well tolerated by all patients except one, who stopped taking the drug because of epigastric discomfort. None had worsening of parkinsonism or other adverse events. All 13 patients reported subjective improvements in bowel frequency and defecation. Mosapride shortened CTT of the left colon (38.8 to 23.5 hours, p<0.01) and the total colon (107.3 to 74.5 hours, p<0.05). During rectal filling, mosapride lessened the first sensation (p<0.05), maximum rectal capacity and the rectal compliance and augmented the amplitude in phasic rectal contraction (not statistically significant). During defecation, mosapride augmented the amplitude in rectal contraction (0.0 to 3.4 cmH2O, p<0.05). The amplitude in paradoxical sphincter contraction on defecation (PSD) and abdominal strain, and the volume of post-defecation residuals decreased (not statistically significant). Concluding message The baseline abnormalities in our parkinsonian patients were in accordance with those in the previous reports [6,7,8]. The present study showed for the first time that mosapride citrate ameliorated constipation in parkinsonian patients without serious adverse effects, which is brought about by augmenting the lower gastrointestinal motility as shown in the CTT and videomanometry.

Fig. 1 Colonic transit time (hours).

107.3

19.7

38.8

44.9

74.5

16.1

23.5

30.7

0

20

40

60

80

100

120

Total colon Right colon Left colon Rectosigmoid

pre post

p<0.05

p<0.01


Fig. 2 Anorectal videomanometry

0.0

32.0

68.2

135.7

3.4

29.5

65.072.9

0

20

40

60

80

100

120

140

160

Prect* (cm H2O) Pana (cm H2O) Pabd (cm H2O) Pos t-defecationres iduals (m l)

pre post

p<0.05

References

1. Inui A, Yoshikawa T, Nagai R, Yoshida N, Ito T. Effects of mosapride citrate, a 5-HT4 receptor agonist, on colonic motility in conscious guinea pigs. Jpn J Pharmacol. 2002;90:313-20.

2. Kii Y, Nakatsuji K, Nose I, Yabuuchi M, Mizuki Y, Ito T. Effects of 5-HT(4) receptor agonists, cisapride and mosapride citrate on electrocardiogram in anaesthetized rats and guinea-pigs and conscious cats. Pharmacol Toxicol. 2001;89:96-103.

3. Asakawa H, Hayashi I, Fukui T, Tokunaga K. Effect of mosapride on glycemic control and gastric emptying in type 2 diabetes mellitus patients with gastropathy. Diabetes Res Clin Pract. 2003;61:175-82.

4. Ruth M, Finizia C, Cange L, Lundell L. The effect of mosapride on oesophageal motor function and acid reflux in patients with gastro-oesophageal reflux disease. Eur J Gastroenterol Hepatol. 2003;15:1115-21.

5. Hallerback BI, Bommelaer G, Bredberg E, Campbell M, Hellblom M, Lauritsen K, Wienbeck M, Holmgren LL. Dose finding study of mosapride in functional dyspepsia: a placebo-controlled, randomized study. Aliment Pharmacol Ther. 2002;16:959-67.

6. Jost, W.H., Schimrigk, K. (1997) Long-term results with cisapride in Parkinson's disease. Mov. Disord., 12: 423-425.

7. Ashraf, W., Pfeiffer, R.F., Park, F., Lof, J., Quigley, E.M.M. (1997) Constipation in Parkinson’s disease; objective assessment and response to psyllium. Mov. Disord., 12: 946-951.

8. Sakakibara, R., Odaka, T., Uchiyama, T., Asahina, M., Yamaguchi, K., Yamaguchi, T., Yamanishi, T., Hattori, T. (2003) Colonic transit time and rectoanal videomanometry in Parkinson’s disease. J. Neurol. Neurosurg. Psychiatry, 74: 268-72.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14501621&dopt=Abstract




38 Culligan P1, Blackwell L1, Murphy M1, Ziegler C2, Heit M1

1. University of Louisville, Division of Urogynecology and Reconstructive Pelvic Surgery, 2. University of Louisville A BLINDED, SHAM-CONTROLLED TRIAL OF POSTPARTUM EXTRACORPOREAL MAGNETIC INNERVATION TO RESTORE PELVIC MUSCLE STRENGTH IN PRIMIPAROUS PATIENTS Hypothesis / aims of study To determine the effects of postpartum extracorporeal magnetic innervation (ExMI) on pelvic muscle strength of primiparous patients for the year following childbirth. Study design, materials and methods Primigravid patients were recruited from our community. Eligible patients were enrolled during their first pregnancy – between 20 and 34 weeks gestation. They were randomized to receive either active or sham ExMI treatments beginning during their 6th postpartum week. Our main outcome measure was pelvic muscle strength as measured by perineometry in cmH2O. These assessments were made by a single independent observer blinded as to patients’ group assignments. Baseline measurements were obtained at the enrollment visits (i.e. while the patients were pregnant), and follow-up measurements were made 6 weeks (prior to ExMI or sham treatment), 14 weeks, 6 months and 12 months postpartum. Between 6 and 14 weeks postpartum, patients completed a course of 16 treatment sessions in either the active or sham ExMI chair (NeoControl®, NeoTonus Inc., Marietta, GA). Our sample size estimate called for 19 patients in each arm to have 80% power of detecting a 40% difference in mean perineometry measures between groups at any point during the study (α = 0.05). Mixed randomized-repeated measures analysis of variance was used to analyze the mean perineometry values between the two treatment groups and across all five time periods. Accordingly, group, time and group cross-time interaction effects were tested. Results Fifty-one patients enrolled, and 38 patients returned for their postpartum treatment sessions. As expected, there were no demographic differences between the active and sham groups. Likewise, there were no differences between the groups with respect to delivery characteristics (i.e. instrumented or C-section delivery, length of labor stages, damage to the perineum, baby birthweight, or episiotomy use). The analysis of variance procedure indicated no main effect difference between the active or sham ExMI treatments, F(1,31)=0.02, p=0.89. Also, there was no significant group cross-time interaction, F(3,88)=2.5, p=0.07, indicating no difference between groups at any given time period. When measures from both groups were combined, an overall time main-effect was found, F(3,88)=4.4, p=0.01. Namely, mean perineometry measures at baseline were significantly higher (mean = 52.2 cmH2O) than those at 6 weeks postpartum (mean = 42.3 cmH2O), p=0.02. However, all subsequent perinometry measurements (14 weeks, 6months and 12 months postpartum) were similar to baseline measurements, p=0.29, p=0.53, p=0.59, respectively. Interpretation of results We found no differences in pelvic muscle strength among primiparous patients who received active or sham ExMI treatments in the early postpartum period. Concluding message Traditional pelvic floor exercises remain the best method for preventing pelvic floor dysfunction following childbirth. ExMI seems to add no muscle strength in this patient population. FUNDING: Neotonus, Inc


39 Masuda H1, Chancellor M1, Kihara K2, de Groat W3, Yoshimura N4

1. Dept of Urology, Univ of Pittsburgh School of Med, 2. Dept of Urology and Reproductive Medicine, Tokyo Medical and Dental Univ, 3. Deptt of Pharmacology, Univ of Pittsburgh School of Med, 4. Dept of Urology and Pharmacology, Univ of Pittsburgh School of Medicine DIFFERENTIAL ROLES OF CENTRAL AND PERIPHERAL NITRIC OXIDE MECHANISMS IN THE REGULATION OF LOWER URINARY TRACT FUNCTION IN THE RAT Hypothesis / aims of study Previous studies have suggested that nitric oxide (NO) released in the bladder and the spinal cord plays an important role in the regulation of the micturition reflex. It has been reported that intravesical administration of NO scavenger decreased bladder capacity inducing bladder contractions in rats, suggesting a local inhibitory effect of NO on bladder activity (1). In contrast, NO centrally released in the spinal cord can induce detrusor overactivity because cystitis-induced detrusor overactivity was reportedly suppressed by intrathecal (i.t.) injection of NO synthase (NOS) inhibitor in rats (2). Thus it seems that NO release in the bladder suppresses the micturition reflex, while NO in the spinal cord facilitates the reflex. However, it is not known how these local and spinal NO mechanisms interact to modulate bladder activity in conscious voiding. Therefore, we examined the effects of NOS inhibition at different sites on bladder activity in rats under an awake condition. We also investigated the involvement of C-fiber afferent pathways in the NO mechanism using awake rats with C-fiber desensitization. Study design, materials and methods Adult female Sprague-Dawley rats (200-230g) were used. An intrathecal (i.t.) catheter was implanted at the level of the L6-S1 spinal cord following a laminectomy at the Th11 vertebra under halothane anesthesia 3 days before continuous cystometry (CMG). Resiniferatoxin (RTX, 0.3mg/kg), a very potent C-fiber afferent neurotoxin, administered s.c. was used for C-fiber desensitization 5 days before CMG recordings. An NO synthase inhibitor, N-nitro-L-arginine methyl ester (L-NAME), was given intravenously (i.v.), i.t. or intravesically during CMG recordings (infusion rate; 0.04 ml/min) in untreated and RTX-pretreated rats under an awake condition. Intercontraction interval (ICI), maximum voiding pressure (MVP) and pressure threshold (PT) were measured. Results In untreated rats, i.v. injected L-NAME (20 mg/kg) did not affect the ICI or PT (n=9), while, i.t. injected L-NAME (1 µmol) significantly (P<0.05) increased the ICI and PT (n=7). In contrast, intravesical instillation of L-NAME (10 mg/ml) decreased the ICI significantly (P<0.05, n=6). D-NAME, an inactive stereoisomer, had no effects in all routes (n=5 in each route). In RTX treated rats, i.v. or i.t. injected L-NAME had no effect on ICI or RT in CMG (n=7 in each). In addition, i.v., but not i.t., injected L-NAME increased the MVP in rats with or without RTX pretreatment, due to increased outlet resistance induced by suppression of NO mediated relaxation of the urethra.(See Figuire 1) Interpretation of results These results indicate that NO released in the spinal cord facilitates the micturition reflex and that this facilitatory effect in the spinal cord is masked by local inhibitory effects of NO on the micturition reflex in the bladder. In addition, these spinal and local effects of NO seem to be predominantly mediated by activation of mechanoceptive C-fiber bladder afferents because both effects were negligible after RTX treatment.


00

ICI (

min

)

(a) iv (20mg/kg) (b) It (1µmol)

10

20NS

10

20

0

10

20*

(b) Intravesical (10mg/ml)

Figuire 1; The effect of L-NAME on the CMG parameters in different routes

*

Before L-NAME After L-NAME

0

20

40

**

MV

P (c

mH

2O)

0

20

40

NS

0

20

40

NS

NS; not significant, * P<0.05, ** P<0.01

00

ICI (

min

)

(a) iv (20mg/kg) (b) It (1µmol)

10

20NS

10

20

0

10

20*

(b) Intravesical (10mg/ml)

Figuire 1; The effect of L-NAME on the CMG parameters in different routes

*

Before L-NAME After L-NAME

0

20

40

**

MV

P (c

mH

2O)

0

20

40

NS

0

20

40

NS

NS; not significant, * P<0.05, ** P<0.01

Concluding message Central and peripheral NO mechanisms have differential roles in the regulation of conscious voiding. Thus it is assumed that imbalance of these two NO mechanisms might be involved in the emergence of detrusor overactivity in pathological conditions. References 1. J Urol 164: 545-550, 2000 2. J Urol 155: 355-360, 1996 FUNDING: National Institutes of Health DK068557 40 Burcher E1, Mansfield K J1, Liu L1, Vaux K J2, Moore K H3

1. University of New South Wales, 2. Royal North Shore Hospital, Sydney, 3. St George Hospital, University of New South Wales, Australia AGE-RELATED DECREASE IN MUSCARINIC M3 BUT NOT M2 RECEPTOR MRNA IN THE MALE DETRUSOR MUSCLE. Hypothesis / aims of study Urodynamic tests have demonstrated an age-related reduction in bladder capacity and increased incidence of detrusor overactivity as well as decreased flow rate and poor bladder emptying (1). In normal adults, bladder contraction is almost entirely due to activation of muscarinic receptors by acetylcholine released from parasympathetic nerves. Functional studies have shown that ageing is associated with a decrease in responsiveness of the detrusor to acetylcholine (2). Radioligand binding results have demonstrated a decrease in the density of muscarinic receptors with age (3) although which specific muscarinic receptor subtype(s) decrease with age has not been determined. The main aim of this study was to determine whether the expression of M2 or M3 muscarinic receptors was altered in ageing, in control patients. Our secondary aim was to determine whether the expression of β-actin was age- or gender-dependent, since this agent is used as an “internal control” in RT-PCR studies.


Study design, materials and methods Biopsies of normal human detrusor were collected from 22 male and 22 female control patients (age range 18 – 88 years) undergoing cystoscopy due to a history of bladder cancer or to asymptomatic haematuria. All patients displayed normal micturition frequency, with no urge incontinence, and no apparent obstruction. Biopsies were taken from macroscopically normal areas of the bladder and were collected into RNA later, dissected into detrusor muscle and mucosa and stored at –70oC until RNA extraction. The expression of M2 and M3 receptor subtypes was quantified using quantitative competitive RT-PCR (QCRT-PCR). To produce competitor RNA for M2 and M3 muscarinic receptors, cDNA fragments (380 and 400 bp respectively) were reverse transcribed and amplified from human bladder mRNA by RT-PCR, and then internally deleted ~20% using restriction enzymes. The modified cDNAs were cloned into a vector and used as templates to synthesise competitor RNA. For QCRT-PCR, bladder RNA (100 ng/tube) was co-amplified with serial dilutions (30 – 0.03 pg/ tube) of competitor RNA, using RT-PCR. The products were then separated by gel electrophoresis (2.5% agarose) and quantified by densitometry. The amount of sample mRNA was determined by plotting the intensity of DNA bands versus the known concentration of competitor RNA. The expression of β-actin mRNA was determined by RT-PCR. The QCRT-PCR data for M2 and M3 receptor expression in detrusor muscle were then normalised for the expression of β-actin in the same sample.

Results The expression of β-actin mRNA did not vary significantly with gender (Fig 1A) or with age (Fig 1B).

0

2500

5000

7500 A

β-ac

tin d

ensi

ty

male female10 30 50 70 90

0

2500

5000

7500 B

age (years)

β-ac

tin d

ensi

ty

Figure 1. Expression of β-actin mRNA in human bladder detrusor. (A) shows no significant difference in expression of β-actin in male and female (P = 0.06). (B), absence of any correlation of β-actin expression with age (r2 = 0.038, P = 0.2, N = 44 males and females). In male patients, the expression of M2 receptors remained relatively constant with age (Fig 2A) whereas the expression of M3 receptors demonstrated a significant decrease with age (Fig 2B, P = 0.003). The mean expression of M3 receptor mRNA was 3.6 ± 1.03 pg mRNA/100 ng RNA (N = 21), whereas that for M2 receptor mRNA was 0.28 ± 0.07 pg mRNA/100 ng RNA (N = 16).

30 50 70 900.00

0.25

0.50

0.75

1.00 A

age (years)

pg M

2 m

RN

A /

100

ngR

NA

30 50 70 900

5

10

15

20 B

age (years)

pg M

3 m

RN

A /

100

ngR

NA

Figure 2. Changes in muscarinic receptor mRNA expression with age, in male control patients. (A), M2 receptor mRNA expression remained constant with age (r2=0.013, P=0.68, N=16). (B), M3 receptor mRNA expression decreased with age (r2 = 38, P = 0.003, N = 21). Interpretation of results In order to correct for any differences in RNA quality, QCRT-PCR results should be normalised to an internal control, and it is important that this does not vary with either gender or age. β-actin is widely used as an internal control and here we show that it is a suitable choice for studies in detrusor muscle. Although it appears that mRNA for M3 receptors was greater than that of M2 receptors, it is not valid to use QCRT-PCR to compare expression of different receptors since different primers and experimental conditions are involved in each case; moreover, mRNA expression is not necessarily linked to protein expression.


Previous radioligand binding studies using the muscarinic ligand [3H]-QNB have demonstrated a decrease in the density (Bmax) of muscarinic receptors with age in the male detrusor (3). In that study, the subtype of muscarinic receptor decreasing with age could not be determined, although M2 and M3 receptors were the main muscarinic receptor types (70% M2: 20% M3). The present study has shown that it is the M3 receptor expression which decreases with age in the male detrusor. Such a hypothesis would be in keeping with the known decrease in contractile responses to acetylcholine in the ageing detrusor (2). In the isolated detrusor, contractile responses to acetylcholine are mediated by M3 receptors. Clinical urodynamic studies in ageing patients have demonstrated several types of lower urinary tract dysfunction. Some of these features, such as decreased contractility and poor emptying, could be the direct result of the decrease in expression of M3 receptor mRNA with age.

Concluding message Radioligand binding studies have revealed an overall decrease in muscarinic receptor density (Bmax) in detrusor with increasing age. We have now shown a specific decrease in expression of M3 but no change in M2 muscarinic receptor mRNA with increasing age. This has not previously been reported. References 1. Urology 51: 206-212, 1998. 2. Exp Geront 36: 99-109, 2001. 3. Neurourol & Urodynamics 22: 527-529, 2003. FUNDING: National Health and Medical Research Council of Australia 41 Levin R1, Whitbeck C1, Chichester P1, Badger W 21. Albany College of Pharmacy and Stratton VAMC, 2. Albany Medical College THE EFFECT OF ACUTE OVARIECTOMY ON RABBIT BLADDER BLOOD FLOW AND OXYGEN TENSION Hypothesis / aims of study Recent studies have demonstrated that urinary bladder structure and function can be significantly affected by alterations in circulating estrogen. In women, reduction of circulating estrogen after menopause has been associated with bladder dysfunction; in rabbits, decreases in circulating estrogen have resulted in mucosal hypoxia, apoptosis, and atrophy. In the present studies, we determined the effect of acute ovariectomy on rabbit bladder blood flow and tissue oxygenation. Study design, materials and methods Female New Zealand White rabbits were ovariectomized and evaluated at 1, 3, and 7 days post-ovariectomy. Sham surgeries were used as controls. Tissue blood flow and tissue oxygen tension were measured in vivo with an Oxylab multi-purpose monitor and probe. This instrument simultaneously measures in real time blood flow in arbitrary Blood Perfusion Units (BPU) and PO2 in mm Hg. Each rabbit was injected 2 hours before the study with 10 mg / kg hypoxyprobe-1. Tissue hypoxia was demonstrated with hypoxyprobe-1 immunohistochemistry. Results Acute ovariectomy resulted in a significant decrease in urothelial oxygen tension as soon as day 1, and a trend toward decreased urothelial blood flow. Bladder muscle did not demonstrate hypoxia post-ovariectomy, and muscle blood flow trended lower at days 1 and 3, returning to baseline by day 7 (see table). Mucosa pO2 Muscle pO2 Mucosa BPU Muscle BPU Control - Sham 16.1 +/- 2.2 11.1 +/- 1.7 1228.0 +/- 156.8 638.6 +/- 105.6 1 Day Ovariectomy 2.7 +/- 1.1 * 11.6 +/- 1.5 1120.8 +/- 127.4 523.6 +/- 103.5 3 Day Ovariectomy 2.6 +/- 0.6 * 12.6 +/- 1.3 970.6 +/- 247.0 420.2 +/- 106.9 7 Day Ovariectomy 5.1 +/- 1.7 * 8.1 +/- 1.4 890.4 +/- 91.7 638.5 +/- 65.7 * = significantly below control, p < 0.05


Hypoxyprobe immunohistochemistry confirmed the presence of urothelial hypoxia and endothelial hypoxia after ovariectomy at all time periods, although the density was significantly lighter at 7 days. Sham surgery did not have any effect on either blood flow or PO2 Immunohistochemistry showed no hypoxia within the bladder muscle or mucosa.

Hypoxy Probe Immunohistochemistry Interpretation of results This study demonstrates that the urothelium is extremely sensitive to acute ovariectomy, with significant urothelial hypoxia seen by post-ovariectomy day 1. Mucosal blood flow also trended lower post-ovariectomy, while the effects on bladder muscle oxygenation and perfusion were small. Short duration physiologic reduction in estrogen in menstruating females may cause similar episodes of hypoxia within the urothelium. Concluding message Sensory nerves are localized in the submucosa, an area that displays frank hypoxia following ovariectomy. We believe that in women, cyclical changes in estrogen that occur during the menstrual cycle may result in cyclical hypoxia within the mucosa and submucosa, and since sensory nerves are very sensitive to hypoxic damage, this may be one of the etiological factors in pelvic pain syndromes and conditions such as interstitial cystitis. FUNDING: Veteran's Administration 42 Hayashi F1, de Groat W1, Roppolo J1, Birder L1, Griffiths D1, Tai C1, Bergamin L1, Wu H1, Kanai A1 1. University of Pittsburgh INCREASED GAP JUNCTION CONNECTIVITY AND FOCAL PACEMAKER ACTIVITY IN THE BLADDER FOLLOWING SPINAL CORD INJURY MAY LEAD TO URINARY INCONTINENCE - REVEALED THROUGH OPTICAL IMAGING Hypothesis / aims of study Detrusor overactivity in humans refers to involuntary contractions during the filling phase of the bladder, when the subject is not intending to void. These contractions may be either spontaneous or evoked and it has been suggested that they may require initiation by a pacemaker. This type of activity is also present normally in the bladders of neonatal rats, but is downregulated during postnatal development when neural mechanisms in the brain emerge as the dominant regulator of lower urinary tract function. However, non-voiding contractions re-emerge in adult rat bladders under abnormal circumstances such as spinal cord injury (SCI) and are believed to be analogous to detrusor overactivity in humans. There have been numerous attempts to characterize bladder pacemaker activity and the mechanism of detrusor overactivity using traditional methods such as cystometry, extracellular, intracellular and patch clamp recording techniques. However, it remains to be determined whether spontaneous excitation in the bladder originates from restricted specialized sites or occurs randomly, how excitation propagates within the smooth muscle and the mechanism underlying detrusor overactivity.


We hypothesize that spontaneous activity in neonates is initiated at a focal pacemaker site and propagates through the detrusor via gap junctions. In the adult, when neuronal innervation of the bladder is complete, this gap junction connectivity is downregulated. We further hypothesize that in spinal cord injury, when neural control is disrupted, gap junction connectivity is upregulated and coordinated spontaneous activity re-emerges. In order to test these hypotheses, we have developed optical imaging techniques to map action potentials and Ca2+ fluxes in the detrusor. The optical setup includes a dual camera photodiode array system that allows us to simultaneously record, at up to 4000 frames/s, action potentials, and intracellular Ca2+ transients from 256 sites in the bladder wall (Fig 1A). Accordingly, our aims were to apply this imaging methodology to investigate the origin(s) of spontaneous activity and the mechanism by which it propagates through the bladders of neonatal, adult, and spinal cord transected rats.

Study design, materials and methods Neonatal (7-21 day-old), adult (4 mo-old) and spinal cord transected (T8-T9; 2 wks after injury) rats were anesthetized and their bladders excised, cannulated, and stained/loaded with voltage (di-4-ANEEPS) and Ca2+ (Rhod-2-AM) sensitive dyes. The bladders were placed in a 37°C bath, connected to a pressure transducer and imaged for spontaneous and electrically evoked optical signals from the ventral, dorsal or lateral surfaces. Isochronal maps (Fig 2A-D) were generated from the local activation time-points for the 256 optical action potentials (using 1st derivative analysis) and intracellular Ca2+ transients (using cross-correlation analysis). An example of the raw intracellular Ca2+ data recorded from the bladder surface and used to generate an isochronal Ca2+ map is shown in Fig 2B. Results In neonatal bladders, a coordinated pacemaker activity originated near the dome resulting in smooth muscle Ca2+ action potentials (conduction velocity = 45 mm/s; not shown) that initiated intracellular Ca2+ transients (4 mm/s) which spread throughout the detrusor (Fig 2A). This resulted in large amplitude (15-25 cm H2O) spontaneous contractions. In adult bladders, spontaneous activity originated at multiple sites (2B) and was of lower amplitude (2-5 cm H2O). Following SCI, a pacemaker site re-emerged at the dome (2C), initiating large amplitude (15-25 cm H2O) spontaneous activity similar to neonatal bladders. Simultaneous blockade of the effects of acetylcholine, ATP, substance P, nitric oxide and �- and �-adrenergic agonists failed to inhibit spontaneous activity in neonatal, adult, or SCI bladders. However, gap junction blockade (glycyrrhetinic acid, 10 �M) reversibly abolished spontaneous activity in neonatal (not shown) and SCI (2C) bladders, but not adult (2D) bladders. Electrical stimulation of neonatal and SCI bladders after gap junction blockade evoked only a small area of depolarization. In contrast, stimulation before gap junction blockers activated a depolarization response that spread throughout the detrusor (not shown). All experiments were carried out in n≥6 bladders.


Interpretation of results Fig 2 shows the spontaneous activity recorded from the ventral surface of an intact neonatal (2A) versus an adult (2B) rat bladder. Three consecutive intracellular Ca2+ transients are shown above their corresponding isochronal grey scale maps to demonstrate the reproducibility of the pattern in the neonate that was lost in the adult. In the grey scale maps, the white areas are the first and black areas are the last regions of the bladder to undergo a Ca2+ transient. In the neonatal bladder there is a repeatable initiation site (pacemaker) while in the adult bladder there are multiple initiation sites that change from one contraction to the next. This reproducibility re-emerges in the transected bladder (2C). Concluding message These findings suggest that gap junctions are necessary for focally initiated large amplitude spontaneous activity in neonatal bladders, and that this connectivity is lost during development and re-emerges following SCI. Spontaneous activity is coordinated, less chaotic and gap junction dependent in bladders from neonatal and SCI rats, but more chaotic and gap junction independent in bladders from adult rats. FUNDING: NIH - NIDDK 43 Nagabukuro H1, Hashimoto T1, Iwata M1, Ishihara Y1, Doi T1

1. Takeda Chemical Industries EFFECTS OF TAMSULOSIN, AN Α1-ADRENERGIC ANTAGONIST, AND TAK-802, A NOVEL ACETYLCHOLINESTERASE INHIBITOR, AND THEIR SYNERGISTIC EFFECTS ON THE URODYNAMIC CHARACTERISTICS IN A GUINEA PIG MODEL OF FUNCTIONAL BLADDER OUTLET OBSTRUCTION Hypothesis / aims of study The efficacy of α1-adrenergic antagonists in the treatment of lower urinary tract symptoms (LUTS) in patients with benign prostatic hyperplasia (BPH) is generally attributable to improvement of the urodynamic characteristics and relief of bladder instability. While the latter effect has been partly confirmed in an animal model with partial bladder outlet obstruction (BOO), the former effect has not been well documented in experimental studies using animals, because no suitable animal model has yet been developed to assess the effects of α1-adrenergic antagonists on the urodynamic characteristics. In this study, we attempted to establish an animal model with functional BOO to model the dynamic component of BPH, and to evaluate the effects of tamsulosin, an α1-adrenergic antagonist, TAK-802, a novel acetylcholinesterase (AChE) inhibitor with some selectivity for muscarinic actions (1), and of both administered concomitantly on the urodynamic characteristics in this model.


Study design, materials and methods Male Hartley guinea pigs (300–380 g) were anaesthetized with urethane (1.4 g/kg, i.p.). Two catheters (PE-100) were inserted into the bladder dome, one for recording the intravesical pressure and the other for intravesical infusion of saline (0.3 ml/min). The intravesical pressure and voided volume were measured using a pressure transducer and electronic balance, respectively. Each signal was concomitantly recorded using an MP100A apparatus (Biopac systems). The signal of the voided volume was differentiated to obtain the flow rate. After confirming at least two successive micturition reflexes induced by intravesical infusion of physiological saline, continuous intravenous infusion of phenylephrine, an α1-adrenergic agonist, was started. The urodynamic parameters were measured prior to and after the drug administration. For evaluation of the effects of tamsulosin and TAK-802, 0.006 mg/animal /min of phenylephrine was administered. The following urodynamic parameters were obtained according to the previous reports (2): maximum flow rate (Qmax), bladder capacity, voided volume, voiding efficiency (=voided volume / bladder capacity×100), maximum intravesical pressure (Pves max) and intravesical pressure at Qmax (Pves(Qmax)). Results Effects of phenylephrine: Continuous intravenous infusion of phenylephrine (0.001-0.006 mg/min/animal) decreased the Qmax and voiding efficiency and increased the Pves max and Pves(Qmax) in a dose-dependent manner (Table). The bladder capacity was not affected by phenylephrine. Table. Effect of continuous infusion of phenylephrine on the Qmax, voiding efficiency and Pves(Qmax) in urethane-anaesthetized guinea pigs. Phenylephrine Qmax (ml/sec) Voiding efficiency (%) Pves(Qmax) (cmH2O) (mg/animal/min) Pre Post Pre Post Pre Post

Vehicle 0.26 ±0.02 0.22 ±0.02 78.5 ±4.3 74.1 ±4.4 22.7 ±1.6 24.1 ±1.3

0.001 0.23 ±0.04 0.15 ±0.02 64.4 ±9.5 57.3 ±8.9 20.7 ±1.0 25.2 ±2.0

0.003 0.28 ±0.04 0.16 ±0.02** 65.9 ±7.6 63.5 ±7.6 20.0 ±1.2 28.7 ±1.6**

0.006 0.28 ±0.02 0.10 ±0.02** 77.6 ±2.9 33.5 ±5.3** 20.5 ±1.0 35.2 ±1.5** Pre and post represent values pre and post drug administration, respectively. Mean ± S.E. **P<0.01, v.s. vehicle-treated group (Dunnett’s test). N=10. Effects of tamsulosin and TAK-802: Tamsulosin (0.003 and 0.01 mg/kg, i.v.) and TAK-802 (0.001 and 0.01 mg/kg, i.v.) increased the Qmax and voiding efficiency in a dose-dependent manner (Figure). The effects were most pronounced in the group that received concomitant administration of both the drugs. When administered alone, tamsulosin decreased, and TAK-802 increased, the Pves max and Pves(Qmax). The effect of TAK-802 of increasing the intravesical pressure was completely abolished by concomitant administration of tamsulosin. Neither of the drugs affected the bladder capacity.

00.001

0.01

0

0.0030.010

0.02

0.04

0.06

0.08

0.100

ml/sec

TAK-802(mg/kg, i.v.)

Tamsulosin(mg/kg, i.v.)0

0.0010.01

0

0.0030.010

0.02

0.04

0.06

0.08

0.100

ml/sec

TAK-802(mg/kg, i.v.)

Tamsulosin(mg/kg, i.v.)

Figure 1: Effects of tamsulosin and TAK-802, and of both administered concomitantly on the Qmax. Both the drugs significantly affected (two-way ANOVA). Each vertical bar represents the mean of the difference between the values pre and post drug administration value. N=12.


Interpretation of results The changes in the urodynamic parameters after phenylephrine infusion are attributable to functional urethral constriction, associated with an increase of the urethral resistance. In this animal model, tamsulosin and TAK-802 improved the Qmax and voiding efficiency possibly via different mechanisms, namely relaxation of the smooth muscle tone of the bladder outlet in the case of tamsulosin, and increase of the bladder contractility in the case of TAK-802. Therefore, concomitant administration of both the drugs probably causes synergistic improvement of the urodynamic parameters. Although lowering the urethral resistance by transurethral resection of the prostate or α1-adrenergic antagonists is the most effective therapy for BPH, pressure flow studies revealed that the LUTS may not necessarily be related to BOO, and may also be affected by detrusor contractility (3). Therefore, concomitant administration of an α1-adrenergic antagonist and an AChE inhibitor might be of superior efficacy in some patients with BPH, even though cholinergic drugs are not widely employed for the pharmacotherapy of voiding dysfunction. The increase in the Pves max observed following administration of TAK-802 may suggest that AChE inhibitors should be withheld in cases with voiding dysfunction caused by obvious BOO with BPH so as to avoid disorders of the upper urinary tract. However, co-administration of this drug with an α1-adrenergic antagonist might reduce this risk, because the effect of TAK-802 of increasing the Pves max was completely abolished by concomitant administration of tamsulosin. Concluding message Tamsulosin and TAK-802 synergistically improved the urinary voiding function in a model of functional BOO. Concomitant administration of an α1-adrenergic antagonist and AChE inhibitor might serve as an effective regimen for the pharmacotherapy of LUTS in patients of BPH. References 1. Effects of TAK-802, a novel acetylcholinesterase inhibitor, on distension-induced rhythmic bladder contractions in rats

and guinea pigs, Eur J Pharmacol, 485: 299-305, 2004 2. Analysis of pressure/flow characteristics in the female rat and their pharmacologic modulation, Neurourol Urodyn, 15:

513-527, 1996 3. Grading of benign prostatic obstruction can predict the outcome of transurethral prostatectomy, J Urol, 160:1713-1717,

1998 44 Yamanishi T1, Yasuda K1, Kitahara S1, Nakanishi K1, Sakakibara R2, Uchiyama T2, Yoshida K1, IIzuka H3 1. Dokkyo University, 2. Chiba University, 3. Mitsubishi Pharma Corporation EFFECTS OF 138-355, A BETA3-ADRENOCEPTOR SELECTIVE AGONIST, ON RELAXATION OF THE HUMAN DETRUSOR MUSCLE IN VITRO Hypothesis / aims of study Beta-adrenoceptors have been demonstrated in the bladder and urethra of several species including human [1,2]. Beta-adrenoceptors are predominantly present in the bladder dome. It has been reported that beta-adrenoceptors mediate relaxation of these smooth muscles in several species, and this relaxation may be mediated via beta1-, beta2- or beta3-receptor or a mixture of these subtypes. Recently, mRNA encoding for the beta3-adrenoceptor has been found in the human detrusor along with that encoding for both the beta1 and beta2-adrenoceptors, and beta3-adrenoceptors have been suggested to have a role in mediating relaxation of detrusor muscles of the human and pig [3]. This study investigates the effects of 138-355, active-matabolite of TT-138 and a beta3- adrenoceptor selective agonist, on relaxation of the human detrusor muscle in vitro. Study design, materials and methods Tissue samples of human bladder muscle from 15 patients undergoing total cystectomy due to bladder cancer were obtained, and the mucosa and serosa were removed. Tissues were mounted in 5 or 10ml organ baths containing Krebs solution, which was gassed with 95%O2 and 5% CO2. Resting tension of 1g was obtained. When the contraction had stabilized, increasing concentrations of beta-adrenoceptor agonists (non-selective, isoprenaline; beta2-selective, clenbuterol; beta3-selective, 138-355 and BRL37344) and propiverine (a non-selective anti-muscarinic antagonist) were added cumulatively and concentration-relaxation curves (CRCs) were obtained. CRCs to 138-355 were obtained in the absence and presence of SR59230A, a beta3-selective


antagonist, and antagonist affinity values (pA2) were calculated from the Schild plot. The study has been conducted in accord with the Helsinki Declaration. The procedures have been approved by the local ethics committee, and written informed consent was obtained from each patient before entry into the study. Results Isoproterenol, clenbuterol, 138-355 and BRL37344 concentration-dependently relaxed isolated human urinary bladder strips with pD2 (-log EC50 value) being 6.8±0.2, 5.2±0.2, 5.8±0.3 and 5.9±0.3, respectively. On the other hand, propiverine had no relaxation effect. Following antagonist assay revealed that concentration-relaxation curves to 138-355 was competitively antagonized by beta3 adrenoceptor antagonist, SR59230A with a pA2 value of 7.0±0.5 and with a Schild slope of 0.7±0.1. Interpretation of results Both beta2-agonist (clenbuterol) and beta3-agonists (138-355 and BRL37344)relaxed human bladder smooth muscles. But the potency of beta3-agonist was greater than that of beta2-agonist. SR59230A, a beta3-antagonist, antagonized CRCs to 138-355 competitively with a pA2 value of 7.0±0.5, indicating that relaxation response of 138-355 may be via beta3-adrenoceptors. Concluding message 138-355, active-matabolite of TT-138 relaxed urinary bladder via not beta1/beta2 but beta3-adrenoceptor stimuli. References 1. Identification of β-adrenoceptor subtypes in lower urinary tract of the female pig. J. Urol. 168, 2706-2710, 2003. 2. The role of ß-adrenoceptor subtypes in mediating relaxation of the pig bladder trigonal muscle in vitro. Neurourol. Urodyn. 22,338-342. 3. The role of β3-Adrenoceptors in mediating relaxation of porcine detrusor muscle. Br. J. Pharmacol. 135,129-134. Fig.1. CRCs to beta antagonists and propiverine Fig.2. Effects of SR59230A on CRCs to 138-355

Propiverine

BRL37344

Clenbuterol

Isoproterenol

138-355

100.-4 -5 -6 -7 -8

0.

slope:0.7±0.1pA2:7.0±0.5

control +10-7 SR59230A+10-6 SR59230A+10-5 SR59230A

-4 -

5 -6

-7

-8

20. 20.

40. 40.

60. 60.

80. 80.

100.

138-

45 Dasgupta J1, Elliott R2, Tincello D2

1. University Hospitals of Leicester, 2. University of Leicester DO ARTIFICIAL SWEETENERS AFFECT BLADDER CONTRACTION? Hypothesis / aims of study An epidemiological study by the Leicestershire MRC Incontinence Programme (1) found daily consumption of carbonated soft drinks to be independently associated with the onset of OAB symptoms in the next twelve months (OR 1.62, 95% CI 1.18, 2.22). We therefore investigated the hypothesis that artificial sweeteners, which are important constituents of carbonated soft drinks, modulate detrusor muscle function.


Study design, materials and methods Bladders were removed from male and female Wistar rats (150g-300g) which have been culled in accordance with schedule 1 procedure of the Animal (Scientific Procedures) Act 1986. Bladder muscle strips were suspended in an organ bath perfused with Kreb’s solution at 37°C aerated with 95% oxygen and 5% carbon dioxide. The apex of the muscle strip was attached to an isometric transducer connected to a four-channel oscillograph. Electrical field stimulation (EFS) was delivered by platinum electrodes recessed within the organ bath chamber and connected to a Harvard Dual Impedance Research Stimulator. The effect of increasing concentrations (10-8 M – 10-2 M) of aspartame, sodium saccharine and acesulfame K on the contractile response to a single frequency (10 Hz) of electrical field stimulation was determined. Those concentrations of sweetener found to significantly affect the contraction of rat bladder muscle to 10 Hz were further investigated for their effect on the frequency response curves to electrical field stimulation (0.5 Hz to 60 Hz), in the presence and absence of atropine 10 –6 M. The effects of these sweeteners on responses to carbachol (10-8 M – 10-4 M) were also determined. Statistical analysis was determined by using ANOVA repeated measures; Wilcoxon matched paris and Students t test where appropriate. A value of p<0.05 was considered significant. Results Sodium saccharine and acesulfame k (10-8 M - 10-3 M) both significantly enhanced the contractile response of rat detrusor muscle to 10 Hz EFS by 9%, 11.6%, 12.4%, 13%, 13.4%, 10.5%(p<0.01) and 7%, 8.6%, 8.1%, 8.83%, 10%, 10.4%, 11.4% (p<0.01) respectively, compared to control (Fig.1). Sodium saccharine 10-8 M increased the maximum response of rat bladder muscle to 40Hz EFS by 10% compared to control and also the atropine resistance response to EFS was increased by 14% (Fig. 2). Sodium saccharine 10-7 M had little effect on the carbachol dose response curve although the maximum response was enhanced by 5%. Acesulfame K 10-8 M enhanced the maximum contractile response to EFS by 9% and also the atropine resistant response to EFS by 7.5%. The carbachol evoked response was also enhanced by 7.3% in the presence of acesulfame K 10-7 M. Aspartame 10-7 M had little effect on the atropine resistant response to EFS although the maximum response to EFS in the presence of atropine was enhanced by 5.6%. Aspartame 10-7 M also slightly enhanced the maximum response to the frequency response curve by 4.5%. The maximum contractile response to carbachol was however significantly increased by 11% (p<0.05) in the presence of aspartame 10-8 M.

0 10 20 30 40 50 60 70

0

1

2

3

4

5

6

ControlAtropine10-6 MAtropine10-6M +Sodium Saccharine 10-8M

*

Frquency (Hz)

Tens

ion

(g)

cont 10-8 10-7 10-6 10-5 10-4 10-30

2

4

6

8

*

** ** ** ** **

Sodium Saccharine conc (M)

Tens

ion

(g)

Interpretation of results Sodium saccharine, acesulfame K, and to a lesser degree aspartame, significantly enhanced the amplitude of the contractile response of rat bladder muscle. The mechanism for this appears to be via an effect on the atropine resistant response to EFS, now known as the purinergic component, which is activated by ATP released from the nerves. Aspartame appears to have more of an enhancing effect on the contractile response to carbachol indicating either a receptor effect or an effect on intracellular calcium movement. Concluding message These sweeteners are found in abundance in many foods and soft drinks. It is therefore possible that sweeteners, and other components of soft drinks, may have direct effects on bladder function as demonstrated so far in our study. The likely concentration of these substances in the human bladder and their effect in vivo remains to be determined. References 1.The association of diet and other lifestyle factors with overactive bladder and stress incontinence: a longitudinal study in women. [Journal Article] BJU International. 92(1): 69-77, 2003 Jul.


46 Yamada S1, Oki T1, Sakakura K1, Komoto I2, Yoshida K2, Kimura R1

1. Department of Biopharmaceutical Sciences, School of Pharmaceutical Sciences, University of Shizuoka, 2. Pharmacokinetics Research Lab., Taiho Pharmaceutical Co.Ltd. DECLINE OF SALIVARY MUSCARINIC RECEPTOR BLOCKING ACTIVITY OF PROPIVERINE HYDROCHLORIDE BY THE LONG-TERM ADMINISTRATION Hypothesis / aims of study Anticholinergic agents such as oxybutynin are widely used for the treatment of overactive bladder (OAB) which is characterized by symptoms of increased frequency of micturition and urge urinary incontinence [1]. However, the major problems with its use are uncomfortable systemic side effects such as dry mouth that can lead to the discontinuation of treatment. Propiverine hydrochloride (Prop) is commonly used for the therapy of OAB [2]. Recently, Noguchi et al. [3] have reported the interesting finding by using visual analog scale, that the feeling of thirst in OAB patients was significantly decreased by 4 weeks consecutive treatment with Prop than the 2 weeks treatment [3]. This clinical observation leads to the idea that the long-term treatment with Prop may cause a significant alteration in the muscarinic acetylcholine receptor (mAChR) binding characteristics of this drug in the salivary gland. To test such assumption, we characterized mAChR binding in the submaxillary gland excised from rats receiving the repeated oral treatment with Prop. Moreover, the pilocarpine-evoked salivary secretion and tissue drug concentration in these rats were simultaneously measured. Study design, materials and methods After receiving oral administration of Prop for 2 and 4 weeks, rats were sacrificed by the exsanguination from descending aorta, and the submaxillary gland was excised. mAChR in the tissue homogenate was measured by radioreceptor binding assay with [N-methyl-3H]scopolamine (NMS) as a radioligand, and binding parameters of apparent dissociation constant (Kd) and maximal number of binding sites (Bmax) for [3H]NMS were estimated by Scatchard analysis. The tissue concentration of Prop was measured by the method of LC/MS/MS. Also, the pilocarpine (0.1-10 mg/kg, i.v.)-evoked salivary secretion was measured in rats receiving oral Prop. Results A significant increase in Kd for specific [3H]NMS binding in the submaxillary gland of rats without a change in Bmax was observed by the repeated oral administration of Prop (3, 30 mg/kg) for 2 weeks. However, interestingly, similar administration of this drug for 4 weeks caused a significant increase in Bmax for [3H]NMS binding in this tissue with little change in Kd. Also, the inhibitory effect by Prop of pilocarpine-evoked salivary secretion was significantly decreased in rats administered orally this drug for 4 weeks, compared with the inhibition due to a single treatment, and this attenuation by the Prop treatment was more prominent in the salivation of lower dose of pilocarpine. The tissue concentration of Prop was little different between 2 and 4 weeks in the submaxillary gland of rats received repeated oral administration of this drug. Interpretation of results These data suggest that repeated oral administration of Prop for 4 weeks compared with 2 weeks causes a significant decline of mAChR binding activities in the submaxillary gland and the concomitant up regulation of the receptor density. Furthermore, the repeated administration of Prop for 4 weeks may reduce significantly the inhibitory effect by this drug of pilocarpine-evoked salivation. It seems unlikely that these effects due to the repeated Prop treatment are ascribed to the altered content of this drug in the submaxillary gland. Concluding message The present study has provided the pharmacological evidence to support the idea that the long-term therapy with Prop in OAB patients may be beneficial in terms of reducing the extent of dry mouth. References[1] Yarker YE. et al.: Oxybutynin. A review of its pharmacodynamic and pharmacokinetic properties, and its therapeutic use in detrusor

instability. Drugs & Aging 6: 243-262, 1995. [2] Madersbacher H, et al.: Efficacy, tolerability and safety profile of Propiverine in the treatment of the overactive bladder (non-neurogenic

and neurogenic). World Urol 19: 324-335, 2001. [3]Noguchi M, et al.: Differential pharmacokinetics between salivary glands and bladder detrusor muscle with propiverine hydrochloride on

over active gladder patients. The International Continence Society 33nd Annual Meeting (Florence), Abstract, pp.323-324, 2003.


47 Hoyte L1, Jakab M2, Shott S 3, Brubaker L1

1. Loyola University Medical Center, 2. Harvard Medical School, 3. Rush University DOES YOUR BONY PELVIC SHAPE DETERMINE YOUR PELVIC SOFT TISSUE DESTINY? RESULTS OF A 3D MRI STUDY. Hypothesis / aims of study Aim: To compare quantitative relationships between soft tissue and bony pelvic measures in nulliparous and vaginally parous women. Null hypothesis: There is no difference in pelvic bony shape, soft tissue position or levator ani geometry in nulliparas compared to vaginal paras. Secondary hypothesis: There is no correlation between pelvic soft tissue geometry and bony pelvic shape in nulliparas or vaginally parous women. Study design, materials and methods Nineteen women from a single gynecology practice underwent pelvic proton density axial MRI for clinical reasons unrelated to pelvic floor disorders. MR-based 3D reconstructions were made of the pelvic bony and soft tissues, and pre-determined parameters were measured. Nulliparous (N=9) and vaginally parous women (N=10) were compared with respect to bony pelvic width, depth, pubic arch angle, urethral angle, bladder neck position, levator shape, volume, and integrity. Among paras and nulliparas, correlations between bony pelvic width, depth, and pubic arch angle were computed with respect to soft tissue measures. Significant correlations were confirmed by scatterplot analysis. Nonparametric statistical testing was performed with a 0.05 significance level. Results Age, parity, and BMI parameters for the groups are detailed in Table 1. Table 2 presents those parameters with significant differences between the groups. Significant correlations and trends are presented in Tables 3a,b. Table 1: BMI, age, and vaginal parity in nulliparas and paras

GROUP BMI AGE VAGDEL Mean 24.58812 28.30 Median 22.86776 27.00 Std. Deviation 5.318749 5.889 Minimum 19.036 20

nullip N=10

Maximum 36.026 39

N/A

Mean 25.34915 37.67 2.11 Median 23.93792 36.00 2.00 Std. Deviation 5.562998 11.769 0.928 Minimum 18.452 25 1

parous N=9

Maximum 35.761 65 3

BMI: Body mass index. AGE: Age at time of MRI. VAGDEL: vaginal parity Table 2: Pelvic 3D parameters having significant differences between nulliparas and paras

GROUP PCL BNPCL LHW LSGL LSGR Mean 91.362 12.8510 32.5640 20.0020 20.6440 Median 95.395 11.8450 32.7200 19.9450 21.4200 Std. Deviation 8.4813 4.92913 2.56144 2.05441 3.27148 Minimum 73.0 4.94 27.31 16.79 15.22

nullip N=10

Maximum 99.6 20.48 36.00 23.09 24.22 Mean 99.399 4.5400 38.7967 30.5111 27.5533 Median 99.300 8.2000 36.5300 32.3000 29.9000 Std. Deviation 5.5439 10.05470 7.06671 6.25566 6.24648 Minimum 89.8 -12.50 29.25 21.01 18.69

parous N=9 Maximum 109.4 18.77 49.40 41.70 35.20 p .022 .041 .022 .001 .050


PCL: pubo-Coccygeal line is anteroposterior distance from symphysis to tip of coccyx. BNPCL: Perpendicular distance from bladder neck to PCL: (positive values lie above PCL, negative values lie below PCL) LHW: Maximal transverse distance of the levator hiatus, LSG(levator Symphysis Gap): distance from inferior mid pubic symphysis to nearest occurrence of puborectalis muscle on left (LSGL), and right (LSGR). Table 3a: Correlation of age, BMI, and pelvic inlet width with levator measures in the parous group

GROUP Parameter

Spearman’s rho & 2 tailed significance LHH LHW LSGL

LSGR

Rho .550 .667 .783 .733 AGE p .125 .050 .013 .025

Rho -.050 .383 .667 .617 BMI p .898 .308 .050 .077

Rho .683 .533 .517 .500

Parous N=9

INTERACET

p .042 .139 .154 .170

BMI: Body Mass Index. INTERACET: Interacetabular bony pelvic distance. LHH: anteroposterior distance from symphysis to levator median raphe. LSGL, LSGR: see table 2. No statistically significant correlations were seen in the nulliparous group. Table 3b: Correlation of bony pelvic and soft tissue measures in nulliparas and paras

GROUP Bony parameter

Spearman’s rho 2 tailed signific. BNPCL BNSYM UREANG URETHRA UREVOL

rho -.188 -.248 -.297 .333 .867 INTERSPI p .603 .489 .405 .347 .001

rho .042 -.345 -.333 .467 .818

Nullip N=10

INTERACET p .907 .328 .347 .174 .004

Rho -.929 .770 .644 -.770 -.510 PCL p .000 .015 .061 .015 .160

Rho -.850 .633 .400 -.783 -.617 INTERTUB p .004 .067 .286 .013 .077

Rho -.800 .633 .433 -.750 -.600

Parous N=9

INTERSPI p .010 .067 .244 .020 .088

PCL: see table 2. INTERACET: see Table 3a. INTERTUB: Intertuberous distance. INTERSPI: Interspinous distance. BNPCL: Table 2. BNSYM: distance between bladder neck and pubic symphysis. UREANG: angle formed by long axes of urethra and pubic symphysis. URETHRA: urethral length. UREVOL: urethral volume Interpretation of results Statistically significant differences between parous and nulliparous women were found with respect to pelvic soft tissue geometry and left puborectalis disruptions. Among parous women, increasing bony pelvic width and depth were correlated with a lower bladder neck, and lengthening of the levator hiatus at rest. These correlations were not observed among nulliparas. Our findings need confirmation by larger studies with well characterized participants. However, these pilot results suggest that childbirth-related pelvic soft tissue changes are related to a deeper, wider bony pelvis. Concluding message Bony pelvic geometry may be a risk factor for childbirth related soft tissue damage. Further studies are needed to determine if bony pelvic architecture is altered by the childbirth process. FUNDING: National Institutes of Health, American Urogynecologic Society


48 Abrams P1, Mattiasson A 2, Van Kerrebroeck P3, Robertson G4

1. Department of Urology, Bristol UK, 2. Dept. of Urology, Lund, Sweden, 3. Dept. of Urology, Maastricht the Netherlands, 4. Dept. of Medicine, Chicago IL, USA NOCTURNAL POLYURIA IS A KEY FACTOR IN NOCTURIA Hypothesis / aims of study Nocturia is one of the most prevalent urological symptoms. The aim of the present study was to assess the frequency of nocturnal polyuria (NP) in individuals with nocturia (waking at night one or more times to void) and to determine if it differs with gender or age (< 65 years and > 65 years). Study design, materials and methods The analyses were performed on basal 7-day frequency/volume charts from 1,003 individuals with nocturia (519 males, 484 females) > 18 years who were recruited into three short-term studies investigating the efficacy and safety of oral desmopressin (1, 2, 3). All patients had > 2 voids per night by history. Night was defined as the period of sleep. Nocturnal polyuria was defined in 3 ways: one was that advocated by the ICS- the proportion of total urine output excreted at night. The night time urine output excluded the last void before sleep but included the first void in the morning. Since the normal range for this value increases with age from < 20% to <33% and the mean age of our patients was 63 years, we used a percentage >33% as indicating NP. The other two definitions of NP were based on absolute rates of urine production before and after adjustment for differences in patient size. In this case, NP was defined as a nocturnal diuresis rate > 0.9 mL/min or > 0.9 mL/min/70 kg based on values previously reported for healthy, adults without nocturia. Results The frequency of NP in patients providing records that were evaluable for each of the 3 definitions (N) ranged from 74 to 85%. If the patients with non-evaluable records were included as non-polyurics, the proportion with polyuria decreased but still ranged from 63 to 73%. Total N NP

Present Relative nocturnal polyuria (> 33% of total 24-h urine volume) 845 74%

Absolute nocturnal polyuria (≥ 0.9 mL/min)

869 85%

Absolute nocturnal polyuria weight adjusted (≥ 0.9 mL/min/70kg)

869 79%

The frequency of NP in patients with evaluable records above the age of 65 years was variably greater than in those below 65 years by all 3 definitions. Even so, most of the young nocturics also had NP with the highest relative values yielded by the two absolute definitions. As before, when the patients with non-evaluable records were included as non-polyurics, the incidence of NP decreased in both age groups but still ranged from 52 to 71% in the young and from 72 to 77% in the old. Age < 65 years

N %NP > 65 years N %NP

Relative NP (> 33% of total 24-h urine volume) 63% 90%

Absolute NP(< 0.9 mL/min)

83% 86%

Absolute NP weight adjusted (< 0.9 mL/min/70kg) 76% 89%


The frequency of NP in male and female patients with evaluable records differed slightly depending on the definition but was not different overall. The largest difference was observed when the weight adjusted absolute definition was used. This resulted in a modestly lower proportion of NP in males than in females because the males tended to be heavier than the females. However, when the relative definition of NP was applied, the gender difference appeared to be reversed- i.e. it was slightly higher in males than females. When the patients with non-evaluable records were included as non-polyurics, the overall frequency of NP decreased in both genders but, depending on the definition was still 66 to 75% in males and 57 to 72% in females. Gender

Males N %NP

Females N %NP

Relative NP (> 33% of total 24-h urine volume) 78% 70% Absolute NP (< 0.9 mL/min) 84% 85% Absolute NP weight adjusted (< 0.9 mL/min/70kg) 74% 84% Interpretation of results The majority of all nocturic patients of both sexes and all ages have nocturnal polyuria by any of the three most widely used definitions.This conclusion applies even if the highly conservative approach of arbitrarily designating all patients with non-evaluable records as non-polyurics is used. The frequency of NP is greater in the elderly than the young but the magnitude of the difference depends heavily on the definition employed. The frequency of NP in males and females also appears to depend on the definition used but overall it appears to be quite similar. Thus, in comparing studies of NP, it is important to consider the impact of the definition employed on the results. None of these analyses take into account possible variations in the duration of sleep. Concluding message Nocturia is one of the most troublesome symptoms of Lower Urinary Tract Symptoms (LUTS); it significantly compromises sleep and HRQoL. This study shows that the majority of all patients with nocturia have nocturnal polyuria. It emphasizes the importance of using frequency/volume charts, as the management of patients with nocturnal polyuria is likely to be different from that of patients without nocturnal polyuria. FUNDING: Ferring Pharmaceuticals A/S 49 Kojima Y1, Sasaki S 1, Kohri K1, Shinoura H2, Tsujimoto G3

1. Dept of Nephro-urology, Nagoya City University Graduate School of Medical Sciences, 2. Dept of Molecular, cell Pharmacology, National Research Institute for Child Health Development, 3. Dept of Genomic Drug Discovery Sciences, School of Pharmaceutical Sciences, Kyoto University CORRELATION BETWEEN ALPHA1-ADRENORECEPTOR SUBTYPE MRNA EXPRESSION LEVEL AND EFFICACY OF NAFTOPIDIL FOR BPH PATIENTS Hypothesis / aims of study Three subtypes of alpha1-adrenoreceptors (alpha1-ARs) have been identified by both pharmacological and molecular cloning techniques. Some reports that the alpha1A-AR and alpha1D-AR subtypes are the predominant subtype compared with alpha1B-AR in the prostate. However, these expression levels seem to vary with each patient. We examined the quantified each alpha1-AR subtype mRNA in BPH tissue obtained by prostate biopsy and correlation of the efficiency of subselective alpha1D-blocker, naftopidil in the management of benign prostatic hyperplasia (BPH). Study design, materials and methods A total of 28 men 50 years old or older (mean age; 67.9+/-6.9 years) with lower urinary tract symptoms secondary to untreated BPH who had undergone a transperineal ultrasound prostate biopsy were enrolled in this study. Four biopsy specimens were obtained from the transition zone, and real-time RT-PCR was performed using these samples to examine the expression level of alpha1A-AR and alpha1D-AR. Judging from the results of real-time RT-PCR, the patients were grouped into alpha1A-AR-dominant patients (n=12) and alpha1D-AR-dominant patients (n=16). After biopsy, they were treated with 50 mg naftopidil for 12 weeks


and were evaluated for the efficacy ( I-PSS, QoL index, Qmax and PVR) of naftopidil at 12 weeks. We examined the correlation between alpha1A-AR and alpha1D-AR mRNA expression level and efficacy of naftopidil. Informed consent was obtained from all patients before this study. Results Naftopidil significantly relieved lower urinary tract symptoms and significantly increased Qmax from baseline. Naftopidil improved IPSS, QoL index and Qmax in alpha1D-AR-dominant patients with a significance differences in comparison with the alpha1A-AR dominant patients. Interpretation of results Subselective alpha1D-blocker, naftopidil was shown to provide significant advantage in the treatment of alpha1D-AR-dominant BPH patients. Concluding message This study confirmed that the expression level of each alpha1 AR subtype mRNA can be a predictor of the efficiency of naftopidil in the management of BPH.

alpha1A-AR dominant �1D-AR dominant baseline 3-month P value baseline 3-month P value

Total IPSS 16.8 (7.8) 8.3 (5.4) 0.001 12.4 (7.3) 6.2 (4.2) 0.002 Voiding frequency 3.3 (1.7) 1.8 (1.1) 0.04 2.2 (1.8) 1.3 (1.4) NS Urgency 1.3 (2.0) 0.7 (1.2) NS 1.1 (1.1) 0.5 (0.7) 0.01 Nocturia 2.3 ((1.2) 1.5 (1.2) NS 2.1 (1.4) 1.5 (1.5) 0.05 Intermittency 1.8 (2.3) 1.3 (1.4) NS 1.8 (1.8) 0.9 (1.3) 0.05 Weak stream 2.7 (2.0) 1.5 (1.5) NS 2.3 (2.1) 1.2 (1.4) 0.01 Hesitancy 2.3 (2.3) 0.8 (0.9) NS 1.1 (1.9) 0.3 (0.5) NS Emptying 3.3 (0.8) 0.8 (1.0) 0.001 1.8 (1.7) 0.6 (0.7) 0.01 QOL 3.9 (1.5) 2.8 (1.8) 0.05 3.4 (1.0) 2.3 (1.2) 0.0004 Qmax 9.3 (3.31) 13.1 (6.4) 0.03 8.5 (3.1) 13.5 (7.1) 0.005 50 Kim J C1, Park E Y1, Seo S I1, Park Y H1, Hwang T1

1. Dept. of Urology, Kangnam St. Mary's Hospital, The Catholic University of Korea DETRUSOR OVERACTIVITY AND CONNEXIN EXPRESSION IN PATIENTS WITH BLADDER OUTLET OBSTRUCTION DUE TO BENIGN PROSTATIC HYPERPLASIA Hypothesis / aims of study Bladder outlet obstruction is a common medical disorder which leads to rearrangements of smooth muscle and epithelial cells of the bladder wall and to alterations in their function. Detrusor overactivity and storage symptoms are frequently associated with bladder outlet obstruction and this may be related with increased electrical coupling. Connexins (Cx) constitute a family of transmembrane proteins that form gap junction channels allowing metabolic and electrical coupling of cellular networks. This study was performed to evaluate the changes of connexin 26 (Cx26) and connexin 43 (Cx43) expression in bladder and whether these changes are related to detrusor overactivity in patients with bladder outlet obstructin due to benign prostatic hyperplasia (BPH). Study design, materials and methods The study groups included 36 male patients who have bladder outlet obstruction due to BPH and received transurethral resection of protate (TUR-P). The pre-operative evaluation included history taking, urinaysis, international prostatic symptom score (IPSS), transrectal sonogrphy, PSA, and urodynamic study. On the basis of the urodynamic results, the patients was divided into two groups according to the presence of detrusor overactivity (DO): DO(+) and DO(-) group. The cases that the maximal bladder capacity was less than 200ml or that have uninhibited detrusor contraction were difined as DO(+) group. The symptoms, IPSS (voiding and


storage symptom score), prostate size, PSA value, and urodynamic parameters were compared in two groups. The bladder mucosal biopsy was performed in the posterior wall of the bladder from all patients during TUR-P. The expressions of Cx26 and Cx43 mRNA in two groups were analysed by reverse transcriptase polymerase chain reaction (RT-PCR). To localize both Cx26 and Cx43 proteins, immunohistochemical staining was performed. Results 14 (38.9%) of the 36 patients presented detrusor overactivity in urodynamic study. From the analysis of symptom, the incidence of urge incontinence in DO(+) group was higher than that of DO(-) group (P<0.05). However, the number of nocturia, prostate volume, PSA value, and IPSS were not different between DO(+) and DO(-) groups. The maximum bladder capacity and PdetQmax were low in DO(+) group compared with DO(-) group on urodynamic study (P<0.05). However, the Qmax and residual volume were not significantly different between DO(+) and DO(-) groups. In the RT-PCR, the Cx26 and Cx43 mRNAs were detectable in all tissue. The RT-PCR analysis demonstrated that the levels of both Cx26 and Cx43 mRNA were significantly increased in DO(+) group compared with DO(-) group (P<0.05). The immunohistochemical staining showed that the Cx26 and Cx43 were localized in the mucosal layer, especially Cx26 in urothelium and Cx43 in suburothelial area, respectively. The staining intensity of Cx26 and Cx43 were increased in DO(+) group compared with DO(-) group. Interpretation of results The expressions of the connexins in mucosal layer are modulated under conditions of detrusor function in bladder outlet obstruction. We observed that the expression of both Cx26 and Cx43 increased at both transcript and protein levels in DO(+) group. The elevated level of connexins can lead to the formation of larger or more gap junctions in the mucosal layer. Therefore, these gap junctions may provide pathways for cell-to-cell communication, and result in activation of sensory transduction. Concluding message The present data demonstrate that the increased Cx26 and Cx43 levels in mucosal layer may be related to overactive bladder symptom and detrusor overactivity in patients with bladder outlet obstruction due to BPH. 51 Valentini F1, Besson G 2, Nelson P 21. E349 INSERM-Université Pierre et Marie Curie Paris FRANCE, 2. E349 INSERM-Paris FRANCE IS EVALUATION OF URETHRAL OBSTRUCTION AND DETRUSOR FORCE POSSIBLE FROM COUPLING OF DATA FROM ONE FREE UROFLOW AND ONE PENILE CUFF TEST IN PATIENTS WITH BENIGN PROSTATIC ENLARGEMENT (BPE)? PRELIMINARY STUDY. Hypothesis / aims of study A technique for noninvasive measurement of isovolumetric bladder pressure has been developed in Newcastle [1]. Our purpose was to show that, by using the VBN mathematical micturition model [2], data from one free flow and one cuff test are sufficient to evaluate the detrusor pressure at maximum flow rate (pdet.Qmax) and thereby usual obstruction indices such as the Abrams-Griffiths (AG) number. Study design, materials and methods We studied 42 male patients attending with lower urinary tract symptoms. Each underwent one pressure-flow study (PF), one pressure-flow study with cuff test (PFC) and one free cuff test without vesical pressure measurement (FC). Applying the VBN mathematical micturition model [2] to urodynamic recordings, one can determine two parameters that characterize the obstructive status of a patient:

(i) the prostatic urethra counter-pressure (pucp) is the pressure exerted on the urethra by the enlarged prostate (equivalent to prostatic opening pressure);

(ii) the detrusor force coefficient (k) quantifies the detrusor function and so the effect of the urethral obstruction on the muscle function.


To analyze cuff recordings, we used a slightly improved version of the VBN model which makes a distinction between intra- and extra-abdominal compartments. This is necessary since the flow controlling zone moves from the prostate to the penile urethra as the cuff is inflated. We applied the VBN model according to the following procedure: 1) Since the cuff test is non-invasive, we used the PF study simply to obtain a free flow trace FF. VBN analysis of this trace does not give absolute values of k or pucp, just a relationship between them. In addition we used the PFC to obtain one free cuff test FC2. 2) Using the standard cuff test analysis, we determined the cuff pressure required to arrest flow for each inflation cycle. These cuff pressures give one or more point estimates of isovolumetric bladder contraction pressure pves,isv. Since bladder contractility varies with time, we also recorded the time or times at which flow interruption occurred (tstop). 3) Using these point estimates of pves.isv, we used the VBN model to determine from the P-F study the best fit for k and pucp. 4) Finally, we used to VBN model with these parameters to predict Qmax, the detrusor pressure at maximum flow (pdet,Qmax), and thereby the AG number (pdet,Qmax – 2 Qmax). Results 1) A simple graphical use of the recorded flow and pressure curves of PFC led to evaluate the transmission coefficient T: T = 0.85 +/- 0.15. 2) 30 from the 42 files (70%) were usable. The FC computed flow curves were very alike the recorded ones except during a short time (about 3 seconds) after deflation of the cuff. Then, a spike of flow rate was observed. VBN calculations using unsteady hydrodynamics found spikes shorter than observed. 3) Because of the good fitting of the curves, evaluation of the detrusor pressure was possible for 27 of the 30 files. The main result was that the accuracy of the evaluation was better with the VBN-cuff coupling than with the only cuff. As an example, in a case with Qmax=13 mL/s, the measured and evaluated values of pdet.Qmax in cm H2O were:

measured from PFstudy : 110 cuff test FC: 40 to 93; cuff test FC2 (2 cuff inflations): 65 to 119 and 53 to 118 VBN method from FC: 91 to 127; VBN method from FC2: 80 to 114. Interpretation of results The main problem is the accuracy of the evaluations. The causes of inaccuracy seem to be a) the dispersion of the values of the transmission coefficient T, the presence of the catheter can affect it. b) a delay of roughly 3 seconds which can be due to an instrumental artifact or a change in the compliance of the distal urethra, widens the spikes duration and replaces the brisk interruption of the flow by a smooth curve; thus, tstop is badly defined. c) anxiety of the subjects may cause a delayed opening of the urethra and involuntary contractions of perineal muscles and sphincter. Our method seems able to eliminate the effect of the third cause, to reduce the effect of the second, but cannot reduce the effect of T dispersion. Our method seems able to eliminate the effect of the third cause, to reduce the effect of the second, but cannot reduce the effect of T dispersion. Concluding message Coupling of theoretical analysis and recorded data of penile cuff test allows to discuss the accuracy and the reliability of the method. Theoretical analysis of the recorded data improves the quantitative evaluation of the obstruction due to BPE. References [1] Noninvasive measurement of bladder pressure by controlled inflation of a penile cuff. J Urol 2002. 167: 1344-47. [2] Modelized analysis of pressure-flow studies of patients with lower urinary tract symptoms due to benign prostatic enlargement. Neurourol Urodyn 2003. 22: 45-53.


52 Dubbelman Y D1, Groen J1, Bosch R1

1. Erasmus Medical Center POSTPROSTATECTOMY INCONTINENCE: SIGNIFICANCE OF THE PRE-OPERATIVE URETHRAL PRESSURE PROFILE AND THE ROLE OF PHYSIOTHERAPY Hypothesis / aims of study Urinary incontinence is a major complication of radical retropubic prostate surgery. Its occurrence can, at least partly, be ascribed to a diminished urethral sphincter function. In a prospective study we examined the effect of a radical prostatectomy on the urethral closing function and the role that pelvic floor physiotherapy can play in the recovery of continence. Study design, materials and methods A randomised study, approved by the institutional ethical committee, of the effect of physiotherapy-guided pelvic floor exercises (≤ 9 sessions) versus exercises instructed to patients through an information folder on incontinence after a radical retropubic prostatectomy (RP) was done at our department from February 2000 to December 2003. Patients listed for such an operation and living within about 75 km from our hospital were asked to participate. Men who gave their informed consent were randomised into one of both treatment arms if they were incontinent one week after removal of the stenting transurethral catheter, i.e., if they lost at least 1 gram of urine in the ICS 1-hour pad test or 4 grams in a 24-hour pad test. Patients with positive lymph nodes, however, were excluded. The 1-hour and 24-hour pad tests were repeated 26 weeks after catheter removal. A urodynamic study including urethral pressure profilometry (UPP) before the operation and 26 weeks after catheter removal was also part of the study. The Brown-Wickham method (open-ended 5F catheter, infusion rate 3 ml/minute, withdrawal speed 2 mm/second) was used for the UPP's. Normally, two measurements were done. The mean values of the functional profile length (FPL) and the maximum urethral closing pressure (MUCP) were used for the analysis. Nonparametric tests were used for statistical analysis. Results are given as median values and interquartile ranges. Results Of the 75 patients who gave informed consent, 5 were excluded because of positive lymph nodes (3 men) or the absence of incontinence (2). 70 Patients thus enrolled the study, 7 of whom dropped out because of bladder neck contracture (4), withdrawal of consent (2) or lack of understanding (1, who was probably an illiterate person). The 63 men who completed the study aged 64 (61 - 67) years at surgery. 31 And 32 men were assigned to the physiotherapy group and the folder group, respectively. 10 (32%) And 9 (28%) of them had regained continence at the 26-weeks follow-up mark. The continence rates obtained in both treatment groups were not significantly different (p=0.72 in the chi-square test). The results of the 1-hour and 24-hour pad tests 1 and 26 weeks after catheter removal, categorized to treatment group and symptomatic result after 26 weeks, are summarized in Tables I and II. The UPP data was incomplete in 6 men, mainly because catheterisation was considered too painful or the results seemed unreliable. The FPL and the MUCP highly significantly decreased from 5.6 (4.5 – 6.3) to 1.9 (1.4 – 2.5) cm and from 50 (43 – 64) to 32 (25 – 46) cm H2O, respectively, in the 57 men who underwent the UPP's before surgery as well as after 26 weeks. That means that in this patient group the RP took away an average of 66% of the FPL and 36% of the MUCP. In this respect, no significant differences were found between the two treatment arms. In addition, the FPL values before surgery as well as after 26 weeks were not significantly different between the men who had regained continence and those who still were incontinent. The MUCP values, however, were significantly different (p=0.002) in these two groups (Table III).

Table I. Results of the 1-hour pad test (in grams) 1 Week 26 Weeks Improvement All (63) 24 (4-144) 2 (0-4) 14 (2-132) Physiotherapy (31) 24 (6-132) 2 (0-4) 10 (2-100) Folder (32) 29 (4-158) # 2 (0-4) # 15 (1-140) # Continent (19) 2 (2-10) 0 2 (2-10) Incontinent (44) 56 (13-187) * 2 (2-6) * 38 (2-157) *


Table II. Results of the 24-hour pad test (in grams) In brackets the percentage of men losing less than 10 grams 1 Week 26 Weeks Improvement All (63) 214 (58-574) [ 6%] 6 (0-24) [ 54%] 187 (32-532) Physiotherapy (31) 214 (58-628) [ 6%] 10 (0-25) [ 48%] 164 (30-532) Folder (32) 211 (55-528) [ 6%] 6 (0-23) # [ 59%] 194 (41-510) # Continent (19) 30 (16-200) [21%] 0 [100%] 30 (16-200) Incontinent (44) 377 (141-650) * [ 0%] 17 (6-40) * [ 34%] 279 (95-606) *

Table III. MUCP values (in cm H2O) Pre-operative 26 Weeks Decrease Relative decrease (%) All (57) 50 (43-64) 32 (25-46) 21 (9-27) 35 (21-51) Continent (15) 65 (50-75) 42 (36-52) 21 (7-35) 33 (18-46) Incontinent (42) 46 (41-58) * 30 (23-44) * 21 (9-26) 38 (23-52) *

# *

not significantly different from the physiotherapy group significantly different from those who had become continent

Interpretation of results The symptomatic results with respect to regaining continence were not significantly different between both treatment groups. As the degree of incontinence at the start of treatment and the UPP parameter values were not significantly different either, it must be concluded that an information folder is as effective as physiotherapy. As the pre- and post-operative FPL values were not significantly different between those who still were incontinent after 26 weeks and those who had become continent, the length of the UPP seems to be relatively unimportant in this respect. The MUCP, however, appears to be a relevant factor: the pre- and post-operative values were significantly lower in the group of men who had remained incontinent. Concluding message Postprostatectomy incontinence occurs in nearly all patients, but considerably decreases in the course of the first half year, with 30% of the men becoming continent. A smaller loss of urine during a pad test shortly after the operation is associated with a higher probability to become continent. Physiotherapy has no additional value in comparison with an information folder. An RP takes away about 2/3 of the length of the UPP and 1/3 of its height. Patients with a low pre-operative UPP are at a higher risk to remain incontinent. It might therefore be considered to treat such patients by other treatment modalities rather than by surgery. 53 Dorey G1, Speakman M1, Feneley R1, Dunn C1, Swinkels A 1, Ewings P2

1. University of the West of England, 2. Taunton and Somerset NHST Hospital A RANDOMISED CONTROLLED TRIAL OF PELVIC FLOOR EXERCISES FOR POST-MICTURITION DRIBBLE IN MEN WITH ERECTILE DYSFUNCTION. Hypothesis / aims of study Post-micturition dribble describes an involuntary loss of urine immediately after leaving the toilet and should be distinguished from terminal dribble which describes a prolonged final part of micturition when the flow has slowed to a trickle/dribble. The bulbocavernosus muscle has three functions. It is active during penile erection, it pumps the ejaculate, and it eliminates urine from the bulbar portion of the urethra after the completion of micturition. It was therefore hypothesised that bulbocavernosus muscle weakness would contribute to both loss of erectile function and also to loss of the bulbocavernosus reflex which empties the bulbar urethra after the completion of voiding. It was hypothesised that strengthening the bulbocavernosus muscle along with the pelvic floor muscles would restore erectile function and that functional use of these muscles could replace the post-void reflex which empties the bulbar urethra in normal men. The aim of this study was to compare an intervention group receiving pelvic floor muscle exercises, manometric biofeedback and lifestyle changes with a control group receiving lifestyle changes only in men with post-micturition dribble and erectile dysfunction.


Study design, materials and methods Ethical approval was gained for the trial. Men were included if they had experienced erectile dysfunction for 6 months or more (mean duration 72 months; range 6-360 months). Men were excluded if they had undergone a radical prostatectomy or had neurological impairment. Fifty-five men with erectile dysfunction (median age 59.2 years; range 22-78) were enrolled from a local urology clinic. Twenty-eight subjects were randomised to an intervention group and received pelvic floor muscle exercises including a strong post-void ‘Squeeze out’ pelvic floor muscle contraction, biofeedback and suggestions for lifestyle changes. Men in the intervention group were instructed to gain a penile retraction and scrotal lift during each muscle contraction. Twenty-seven controls were solely advised on lifestyle changes. Lifestyle changes included advice on reducing alcohol levels, stopping smoking, weight reduction, getting fit, and avoiding saddle pressure when cycling. After 3 months of lifestyle changes, the control group received pelvic floor muscle exercises and biofeedback. Both groups were followed up following a further 3 months of home pelvic floor muscle exercises. The post-micturition dribble status, erectile function domain of the International Index of Erectile Function, anal manometry and digital anal muscle grade were assessed at baseline, 3 and 6 months in both groups. An independent assessor who was blinded to the grouping assessed the post-micturition dribble status and erectile function of subjects in both groups at 3 and 6 months. Data was analysed using appropriate tests. Results Thirty-six (65.5%) subjects reported post-micturition dribble at baseline. Of these, 21 subjects were randomised into the intervention group and 15 into the control group. There was significant reduction in post-micturition dribble after intervention (p<0.001) compared to the controls (p=0.102) using a Wilcoxon test. In both groups combined, after 3 months of pelvic floor muscle exercises and 3 months of home exercises, 27 (75%) subjects became asymptomatic of post-micturition dribble, 3 (8.3%) improved, and 5 (13.9%) dropped out. One (2.8%) subject still reported post-micturition dribble. Post-micturition dribble was not correlated to age, erectile function, anal manometric pressure or digital anal muscle grade. At 3 months, erectile function in the intervention group was significantly improved compared to the control group (p=0.001) using a Mann-Whitney independent samples test. After 6 months of pelvic floor muscle exercises, the blind assessment showed that 22 (40%) subjects regained normal er function, 19 (34.5%) improved and 14 (25.5%) failed to improve.

Outcomes of treatment for post-micturition-dribble

43210

0 = drop outs 1 = PMD 2 = less amount 3 = less often 4 = no PMD

Num

ber o

f sub

ject

s

30

20

10

0

* denotes significance (p=0.001) Bar chart showing post-micturition dribble outcomes after pelvic floor exercise Interpretation of results The percentage of subjects with erectile dysfunction who experienced true post-mictgreater than in a study for men with a similar age range (26.9%)(1). Other prevaleterminal dribble. Bulbocavernosus muscle dysfunction may provide an association

ectile *

s

urition dribble (65.5%) was nce studies have included between post-micturition


dribble and erectile dysfunction. The pelvic floor muscle exercise regime included functional bulbocavernosus muscle activity to replace the normal bulbocavernosus reflex at the completion of voiding. This novel functional pelvic floor muscle ‘Squeeze out’ contraction eliminated a few drops of urine whilst subjects were poised over the toilet and should be used in preference to milking the bulbar urethra as in ‘bulbar urethral massage’(2). Pelvic floor muscle exercises should be used as a first line treatment for men with erectile dysfunction. Men receiving other treatments for erectile dysfunction could be instructed to perform pelvic floor muscle exercises. Concluding message Pelvic floor muscle exercises including a post-void ‘Squeeze out’ pelvic floor muscle contraction are an effective treatment for both post-micturition dribble and erectile dysfunction. References 1 (1997) [Incidence of post-micturition dribble in adult males in their twenties through fifties] Acta Urologica Japonica 43 (6): 407-10 (English Abstract) 2 (1997) Pelvic floor exercises as a treatment for post-micturition dribble British Journal of Urology 79:892-897 54 van Voskuilen A1, van Kerrebroeck P 1, van den Homberg U2, Approval Study Group P 31. Academisch Ziekenhuis Maastricht, The Netherlands, 2. Medtronic, Tolochenaz, Switzerland, 3. multicenter LONG-TERM EFFICACY, SAFETY AND QUALITY OF LIFE RESULTS OF SACRAL NEUROMODULATION FOR THE TREATMENT OF VOIDING DYSFUNCTION’S: OUTCOMES FROM A PROSPECTIVE, WORLDWIDE CLINICAL STUDY Hypothesis / aims of study Sacral neuromodulation is established treatment modality for various types of voiding dysfunction. We report the results of a multicenter trial that was designed to evaluate long-term efficacy, safety and quality of life in patients with urge incontinence, retention and urgency-frequency that received Sacral Neuromodulation therapy. Study design, materials and methods Seventeen centers worldwide participated in this long-term study. 156 patients were implanted with InterStim system (Medtronic, Minneapolis). There were 20 males (12.8%) and 136 females (87,2%) and the mean age was 45.0 years ± 11.6 years (18.3 – 79.5). 97 patients (62.2%) had urge incontinence, 25 (16.0%) urgency/ frequency and 34 patients (21.8%) had idiopathic urinary retention. Voiding diaries were collected annually throughout five years. Success was considered as ≥50% improvement in primary voiding diary variables that were separately identified for each patient’s group. Patients who exited the study for the lack of efficacy or adverse event were considered therapy failure and were included in the analysis. Results Five-year data was available from 93 patients. Data from the remaining patients were reported during the intervals from which they were available. Average number of leaking episodes/day for 53 urge incontinent patients went down from 10.2 + 6.4 at baseline to 3.6 + 4.0 after 5 years follow-up. For urgency-frequency patients, the average number of voids/day at baseline decreased from 19.0 ± 6.8 to 13.6 ± 7.1 (n=15) at 60 months. Average volume voided/void at baseline increased from 90.5 ± 50.7 ml to 215.6 ± 166.7ml at 60 months. Average catheterized volume/ catheterization for implanted retention patients decreased from 356.7 ± 172.5 ml to 68.3 + 119.5 ml at 60 months. Important finding is that once a patient is successful after 12 months, there is a high likelihood of continued success up to 60 months: 85.7% for urge incontinence, 83.3% for urgency-frequency and 90.5% for urinary retention. At 60 months follow up, 64.2% of the UI patients, 66.7% of the U/F and 76.0% of retention patients had successful outcomes. SF-36 physical component scores showed significant improvements at 6 and 12 months for UI, 6-36 months for U/F, and 6, 12, 48, and 60 months for UR. SF-36 Mental component scores showed significant improvements at 6 through 36 months for UI and 6 through 36 months for U/F. Beck depression scores, which


indicated mild to moderate baseline depression for UI and U/F patients, showed significant improvements at 6-48 months for UI and 6-36 months for U/F. There were no severe or irreversible adverse events reported and 91.7% of the reported adverse events have been resolved at the time of database closure. Of 156 patients, 100 experienced 30 device-related and 236 therapy related adverse events. Overall, 14 patients were explanted due to an adverse event or lack of efficacy. Concluding message The results of this long-term study demonstrate that InterStim therapy is effective and safe for restoring voiding in patients who are refractory to other forms of treatment. 86.8% of the patients that were successful after one year were still successful after five years. It also shows that patients treated with sacral neuromodulation notice an significant improvement in their quality of life. Other proven advantages of neuromodulation are its reversibility and relative non-invasive nature when compared to surgical alternatives the physician can offer to the patients with refractory lower urinary tract symptoms. SF-36 and Beck over time UI Score Baseline 6 mos 12 mos 24 mos 36 mos 48 mos 60 mos PCS 35.2 39.8* 40.1* 38.3 39.1 36.8 36.5 MCS 44.1 48.9* 49.9* 48.9* 49.0* 47.7 45.1 Beck 13.8 8.2* 8.1* 9.6* 8.5* 10.2* 11.8 U/F Score Baseline 6 mos 12 mos 24 mos 36 mos 48 mos 60 mos PCS 35.0 44.9* 43.3* 45.8* 48.1* 48.0 45.2 MCS 43.0 53.0* 47.9* 52.6* 56.4* 49.8 54.2 Beck 11.5 6.8* 8.6 5.6* 2.5* 5.9 2.7 UR Score Baseline 6 mos 12 mos 24 mos 36 mos 48 mos 60 mos PCS 36.6 42.0* 42.9* 38.0 40.9 42.1* 41.8* MCS 50.8 51.5 50.4 52.8 50.8 51.3 46.3 Beck 7.6 6.1 8.5 6.5 7.2 6.2 8.6 * p < 0.05 FUNDING: Medtronic Europe SARL 55 Hansen J1, Fjorback M V1, Media S2, Nøhr M3, Biering-Sørensen F4, Sinkjær T1, Rijkhoff N J M1

1. Center for Sensory-Motor Interaction, Aalborg University, Denmark, 2. Paraplegic function, Rheumatological Department, Viborg Hospital, Denmark, 3. Department of Urology, Aalborg Hospital, Denmark, 4. Clinic for Para- and Tetraplegia, Copenhagen University Hospital, Denmark AUTOMATIC EVENT DRIVEN ELECTRICAL STIMULATION FOR TREATMENT OF NEUROGENIC DETRUSOR OVERACTIVITY IN SPINAL CORD INJURED PATIENTS Hypothesis / aims of study Neurogenic detrusor overactivity (NDO) is a common urodynamic observation in patients with spinal cord injury (SCI). It is characterised by involuntary detrusor contractions during the filling phase which may be spontaneous or provoked. Patients with NDO often have high intravesical pressures, low bladder capacity and suffer from incontinence. If left untreated the high pressures can lead to upper urinary tract damage. NDO is usually managed conservatively by medication, such as anticholinergic drugs. Many patients are however refractory to this treatment or they cannot tolerate the side effects. In that case surgical options are usually considered to prevent kidney damage. An alternative treatment option is electrical stimulation. It has been shown that electrical stimulation of pudendal nerve afferents can inhibit bladder contractions in SCI patients and that bladder capacity can be increased by continuous [1] as well as conditional stimulation [2].


The aim of this study was to evaluate the feasibility and clinical relevance of automatic event driven electrical stimulation of the dorsal penile/clitoral nerve in treatment of NDO in individuals with SCI. Study design, materials and methods The study was approved by the local Ethics Committee and informed consent was obtained from all patients. A total of 16 SCI patients have been examined (14 M, 2 F). Inclusion criteria were occurrence of NDO at bladder capacities below 500 ml, age over 18 years and complete or incomplete suprasacral SCI. Participants were not asked to discontinue medication prior to participating in this experiment. Stimulation was conducted using surface electrodes placed on the base of the penis or on the clitoris and parameters were: 20 pulses/s, pulse width 200 µs and amplitude two times threshold for elicitation of the bulbocavernosus reflex. Pves and Pabd were measured using a custom made portable device [3] and electrical stimulation was applied based on the calculated Pdet. In each patient 2 sessions of natural bladder filling were monitored:

Session 1: Untreated filling (without stimulation). Session 2: Treated filling (with stimulation applied when Pdet > 10 cmH2O).

During session 2, stimulation was stopped in the following cases:

• Automatically, when Pdet had been under the threshold for a period of 10 s. • Manually, when a leakage was detected (by visual inspection). • Manually, when stimulation had been on for more than 2 minutes without a decrease in pressure.

In order to evaluate the effect of penile/clitoral nerve stimulation 4 parameters where calculated/extracted:

A) Bladder volume at first contraction during treated filling. * B) Bladder volume at the time of leakage in treated filling. ** C) The average peak pressure of Pdet during contractions in the untreated filling. D) The average peak pressure of Pdet during suppressed contractions in the treated filling.

* Calculated on the assumption of linear urine production during the time of treated filling. ** Measured as volume leaked + residual urine at the end of the treated filling. Results Stimulation increased bladder capacity in 13 out of 16 patients (81%). In 2 patients stimulation could not inhibit the first undesired contraction and leakage occurred and 1 patient could not tolerate the stimulation. Figure 1 shows the individual bladder capacities as well as the mean capacity (box) and its standard deviation (T-bar). Figure 2 shows the individual average peak pressure of Pdet during untreated and treated filling together with mean and standard deviation.

Figure 1: Bladder capacity at first contraction and at leakage during treated filling. (Boxes indicate mean value and T-bars indicate standard deviation)

Figure 2: Max detrusor pressure with and without stimulation. (Boxes indicate mean value and T-bars indicate standard deviation)


Interpretation of results Results from the 13 good responders indicate that it is feasible to treat NDO by event driven electrical stimulation. An average bladder capacity increase of 53% was obtained. The average peak detrusor pressure during suppressed contractions in the stimulated filling was 28 cmH2O (range 12 - 55 cmH2O) and is thus sufficiently low to prevent kidney damage. Concluding message In 81% of the patients bladder capacity was increased and storage pressure decreased as a result of automatic event driven electrical stimulation. Although the setup in this experiment is not suitable in the chronic setting, the treatment modality is promising. Today implants stimulating the pudendal nerve afferents are available but they use continuous stimulation. Habituation of the involved reflexes and a reduced life span of the electrodes have been suggested as possible reasons for a timely decline in the number of good responders. This makes it relevant to investigate event driven stimulation. Steps are being taken in order to develop a non-catheter based monitoring of bladder activity, since this is needed in order to apply stimulation automatically. References [1] Bladder inhibition by penile nerve stimulation in spinal cord injury patients,

J Urol, 1992. 147: p.100-103 [2] Conditional stimulation of the dorsal penile/clitoral nerve may increase cystometric capacity in

patients with spinal cord injury, Neurourology and Urodynamics, 2003. 22(2): p. 130-137

[3] A Portable Device for Experimental Treatment of Neurogenic Detrusor Overactivity, Neuromodulation, 2003. 6(3): p. 158-165

FUNDING: Danish research council, Sahva Foundation, Fabrikant Mads Clausen Foundation, European Union: the REBEC project. 56 Voss Fjorback M1, Rijkhoff N1, Petersen T 2, Nohr M 3, Sinkjaer T1

1. Center for Sensory-Moter Interaction, 2. The Centre for Multiple Sclerosis in Ry, 3. Department of Urology, Aalborg Hospital CONDITIONAL ELECTRICAL STIMULATION OF THE DORSAL PENILE/CLITORAL NERVE FOR MANAGEMENT OF NEUROGENIC DETRUSOR OVERACTIVITY IN MULTIPLE SCLEROSIS Hypothesis / aims of study Conditional electrical stimulation of pudendal afferents has been shown to suppress detrusor contractions in patients with neurogenic detrusor overactivity [1][2]. The aim of this study was to investigate whether the involuntary detrusor contractions could effectively be inhibited with event driven electrical stimulation, hereby increasing bladder capacity and reducing storage pressure in patients with Multiple Sclerosis (MS). Study design, materials and methods A total of 10 MS patients with low bladder capacity (< 300ml) and a recent urodynamic study showing detrusor overactivity incontinence participated in the study (6 M, 4 F). The patients were asked to discontinue any pharmacological treatment of NDO a week prior to the experiments. Two natural bladder fillings were carried out in each patient starting with a control filling where no stimulation was applied. Intravesical and abdominal pressures were measured with a fluid-filled CH8 catheter and a rectal balloon catheter. The pressures were sampled at 20 Hz by a portable urodynamic monitoring device [3]. In the second filling automatic conditional stimulation of the dorsal penile/clitoral nerve was applied with surface electrodes whenever the detrusor pressure exceeded 10 cmH2O. When enabled, charge compensated 200 us pulses were applied at 20 Hz at the maximum tolerable amplitude according to the subject under investigation, which was usually 1.5-2 times the threshold for evoking the bulbocavernosus reflex (50-60 mA).


Leaked urine was collected in a diaper and the volume was measured by weighing the diaper. Recording was terminated when leakage had occurred and subsequently the bladder was emptied in order to determine the residual volume. The increase in bladder capacity that could be obtained with electrical stimulation was determined from the volume at first successfully treated contraction and the volume at which leakage occurred. The bladder volume at each point in time was estimated by assuming a constant filling rate during the filling. Results The control filling showed detrusor overactivity in 8 of the 10 patients and in all cases the first untreated detrusor contraction resulted in leakage. In 7 of the 8 patients one or more detrusor contractions could be inhibited by stimulation. Fig. 1 shows an example of the data recorded in a female MS patient with and without conditional electrical stimulation during natural bladder filling. The detrusor pressure and estimated bladder volume is shown at each point in time. During the control session three detrusor contractions occurred that all resulted in leakage (Fig. 1A). During the session with conditional electrical stimulation 89 detrusor contractions were successfully inhibited before stimulation was no longer effective and leakage occurred (Fig. 1B). The first detrusor contraction occurred at a bladder volume of 63 ml in the stimulation session and the patient was continent until a bladder volume of 310 ml was reached. The time from first contraction until leakage was about 40 minutes.

Figure 1: Detrusor pressure and estimated bladder volume during natural bladder filling with (B) and without (A) electrical stimulation. In the 7 patients where bladder inhibition was demonstrated, the average increase in bladder volume from first suppressed detrusor contraction to leakage was 94% (range: 22-366%). In each patient an average of 12 detrusor contractions could be inhibited before leakage occurred. On average, the time from first suppressed contraction until leakage was 15 minutes and 50 s (range: 5 min. – 40 min.) with an average physiological filling rate of 8 ml/min. In all cases urgency was effectively suppressed at the onset of stimulation. Interpretation of results The results indicate that involuntary detrusor contractions in MS patients can effectively be inhibited with conditional stimulation, hereby improving bladder capacity and reducing the number of incontinence episodes. The fact that stimulation is applied may warn the patient that it is time to empty the bladder and bladder emptying can then be planned according to this. The average time of 15 minutes and 50 s from first contraction to leakage would probably suffice in most cases.


Concluding message This study shows that the neurogenic overactive bladder can be inhibited using conditional dorsal penile/clitoral nerve stimulation hereby increasing bladder capacity and reducing the number of incontinence episodes in MS patients. Because the neurological symptoms of MS change over time together with the urological disorders, conditional electrical stimulation of pudendal afferents may prove to be a promising non-destructive treatment option that can be used to avoid or postpone destructive surgery. References 1. The acute effects of continuous and conditional neuromodulation on the bladder in spinal cord injury. Spinal Cord 2001;39:420-428. 2. Electrical Stimulation on the dorsal penile/clitoral nerve as treatment to increase bladder capacity in spinal cord injured patients.

Neurourol Urodyn 2003;22(2):130-7. 3. A Portable Device for Experimental Treatment of Neurogenic Detrusor Overactivity. Neuromodulation 2003;6(3):158-165. FUNDING: Sahva Foundation, Fabrikant Mads Clausen Foundation, and the Danish Multiple Sclerosis Society 57 Freire M1, Almeida F G1, Cedenho A1, Rosa A A 1, Srougi M 1, Bruschini H1

1. Federal University of Sao Paulo

HOW DOES THE URINARY FLOW CLEAN THE URETHRA DURING THE MICTURITION? THE ROLE OF LOW URINARY FLOW ON BLADDER OUTLET OBSTRUCTED PATIENTS.

Hypothesis / aims of study: Studies regarding the urinary sample’s collecting technique have addressed issues such as the first or mid stream clean catching, urethral catheterization and cleaning the perineal area and urethral meatus. However, at our knowledge, there is no study addressing the importance of the urinary flow and how it could clean or avoid urine contamination. In this study, we evaluate the role of the urinary steam on the urethral urinary contamination and how the urinary flow washes the urethra during the micturition, which could justify the need to collect the midstream on urinary testing. Study design, materials and methods: To determine how the urinary flow could interfere on the bacterial urethral contamination, the distal urethra of male patients with indication for urodynamic study (UDS) was scrub using a sterile cotton swab just after the patient had urinated to perform the initial fluxometry. Patients that urinated less than 150 ml or had detrusor hypocontractile were excluded. The swabs were sent to laboratory bacteriological culture tests. After the UDS have been accomplished, the patients were evaluated according to the urinary flow, presence of bladder outlet obstruction (BOO) and swab culture results. Patients were considered obstructed when classified as grade II or greater on Schafer pressure flow classification. To evaluate how the urinary flow washes the urethra during the micturition, we developed an apparatus capable to automatically aliquot the urinary stream in 40 different samples and concomitantly determine the urinary flow and volume. The device was created using a circumferential acrylic plate, which fitted 40 tubes of 50 ml covering the entire external edge. To collect the samples, the subject urinated into a funnel that drove the urine toward the tubes. As the patient urinated, the acrylic plate along with the tubes rotated at a constant speed, which allowed calculating the urinary flow based on the volume collected in each tube. The volume and the number of leukocytes in all 40 tubes were evaluated for all subjects. Using this apparatus, we study the kinetic of leukocyte urinary elimination of 38 asymptomatic volunteers. To evaluate the effect of the urinary stream on the urethral washing, we create a curve of leukocyte elimination during the micturition and compared the number of leukocyte/ml on the first 100 ml with the leukocyte elimination on the left over micturition. Results In table 1, it is outlined the data related to the urethral cultures. Patients without BOO had greater urinary flow (p= 0.003) and lower incidence of positive urethral bacteriological culture (p = 0.02) than their counterparts. Thirty eight asymptomatic male medical students with mean age of 20.2+/-1.3 years old were evaluated regarding the leukocyte elimination. Out of them, 10 subjects presented a urinated volume < 100 ml and 28 subjects presented a volume > 100 ml (table 1). Subjects that eliminated less than 100 ml had lower (p < 0.000) urinary flow than their counterparts (table 1). The 28 young asymptomatic males that urinated more


than 100 ml presented a patron of leukocytes elimination during the micturition (figure 1), unlike those that urinated less than 100 ml (figure 2). Analyzing the 28 subjects that urinated a volume > 100 ml, we observed that the first 100 ml of micturition had a higher (1439.1 leukocytes/ml) mean leukocytes’ concentration than the subsequent micturition (404.7 leukocytes/ml; p < 0.000). Interpretation of results In this study, we address the importance of urinary flow on urethral washing during the micturition. This variable, intuitively, has a role on the urethral cleaning, urinary tract infection prevention and may be an influence on the urinary tests results. However, there is a lack of studies to evaluate it. We choose to study the leukocyte urinary elimination on health subjects, which had a normal urinary flow, because leukocyte could demonstrate better than any other urinary component how the flow washes the urethra. Leukocytes are present in the urine and in the urethra. The patron of leukocytes elimination clearly demonstrated how the the first 100 ml of micturition washes the urethral leukocytes and then stabilizes at a constant concentration during the micturition on subjects with normal urinary flow. In addition, we demonstrated that patients without BOO and normal urinary flow have a lower bacterial contamination on the urethral meatus after micturition, which could be related to the higher incidence of lower urinary tract infection on patients with BOO. The persistent urethral contamination, even after micturition on patients with BOO should be considered as a possible contamination factor, even when it is performed midstream urinary collection. Further studies should be accomplished to evaluate the patron of leukocytes elimination on those patients with some sort of bladder empting disturbs. Concluding message To our knowledge, it is the first time in the literature that it is described the kinetic of leukocyte urinary elimination in asymptomatic health subjects. These results confirm the importance of midstream urinary collecting to perform urinary test, because the first 100 ml of micturition is highly contaminated with urethral leukocytes and may be with bacteria. In addition, we presented the importance of the urinary flow on the urethral bacterial washing. Therefore, we recommend, when it is possible, to collect urinary samples of patients with more than 100 ml in the bladder and instruct patients to urinate at least 100 ml before collect the sample. Patients with BOO may present higher urinary contamination by the urethra, as the low urinary flow did not allow a good urethral washing. Table 1- Comparison of patients with and without BOO. N Age

(mean+/- S.D.) Mean Urinary Flow (mean+/- S.D.)

Positive urethral culture N (%)

With BOO 15 56.7+/-14.4 6.36+/-4.9 14 (93.3%) Without BOO 8 49.4+/-16.1 13.5+/-5.4 4 (50%) Table 2- Comparison of patients that urinated volumes < or > than 100 ml. N Age

(mean+/- S.D.) Mean Urinated Volume

Mean Urinary Flow (mean+/- S.D.)

Mean Max. Urinary Flow

< 100 ml 10 20.2+/-1.5 86.8 11.8 +/-5.1 18.4 > 100 ml 28 20.2+/-1.3 206.7 5.0+/-3.1 11.0 Figure 1- Patron of mean urinary leukocytes elimination of asymptomatic subjects that urinated more than 100 ml.

0500

100015002000

25003000

35004000

0,0 50,0 100,0 150,0 200,0 250,0

volume (ml)

Leuk

ocyt

es/m

l


Figure 2- Patron of mean urinary leukocytes elimination of asymptomatic subjects that urinated less than 100 ml.

0,0

10000,0

20000,0

30000,0

40000,0

50000,0

60000,0

0,0 10,0 20,0 30,0 40,0 50,0 60,0 70,0 80,0 90,0 100,0

volume (ml)

Leuk

ocyt

es/m

l

58 Harding C1, Robson W1, Drinnan M1, Ramsden P1, Griffiths C1, Pickard R1

1. Freeman Hospital, Newcastle-upon-Tyne, UK PREDICTIVE VALUE AND SENSITIVITY TO CHANGE OF NON-INVASIVE PRESSURE FLOW STUDIES Hypothesis / aims of study Transurethral resection of the prostate (TURP) remains the most effective treatment for men suffering from a combination of bothersome lower urinary tract symptoms (LUTS) and reduced urinary flow rate with over 70% achieving good outcome. Previous studies have suggested that the less satisfactory results experienced by up to 30% of patients are due to the presence of undiagnosed detrusor hypocontractility or detrusor overactivity without obstruction (1). It follows that surgical success rates can be improved by performing urodynamic studies to identify men with bladder outlet obstruction (BOO) by plotting simultaneously measured maximum flow rate (Qmax) and subtracted voiding pressure (pdet.Qmax) on a nomogram (2). Unfortunately the invasive and relatively costly nature of conventional cystometry prevents its widespread use in the diagnosis of men with LUTS. A novel non-invasive urodynamic test has recently been developed whereby the pressure within a pneumatic penile cuff required to interrupt voiding (pcuff.int) gives a valid and reliable estimate of isovolumetric bladder pressure (pves.isv). It has been shown that a plot of Pcuff.int and Qmax on a modified ICS nomogram allows accurate non-invasive diagnosis of BOO (Figure 1; 3). The aim of the current prospective study was to determine firstly whether pre-operative classification of men using the putative non-invasive nomogram would predict symptomatic outcome from TURP and secondly whether non-invasive urodynamic parameters from the penile cuff test were sensitive to change following TURP. Study design, materials and methods Ethical approval and informed written consent were obtained. Men selected for TURP using standard clinical criteria completed an IPSS score and underwent standard uroflowmetry together with a penile cuff test immediately prior to and 4 months subsequent to their surgery. The operating surgeon and the patient were blind to the non-invasive urodynamic findings. Following sample size calculation we plan to investigate 200 men and data from the first 72 men who have completed the study protocol form the basis for this interim analysis. Individual pre and post-operative values of pcuff.int and Qmax were read from the non-invasive pressure-flow trace generated by the automated penile cuff device and plotted on the proposed nomogram. A satisfactory outcome from TURP was defined as a greater than 50% decrease in total IPSS. Symptomatic outcome was then related both to the pre-operative non-invasive classification and the individuals change in position on the nomogram following TURP. Results A total of 68 (94%) patients provided pre-operative pressure-flow traces acceptable for analysis. Satisfactory symptomatic outcome was achieved for 48 (71%) men. The 27 subjects with BOO diagnosed from the pre-


operative non-invasive plot (upper left quadrant on nomogram) showed a success rate of 81% compared to 62% in the 13 men deemed not obstructed pre-operatively. Of the 28 men with equivocal findings 18 (64%) reported a satisfactory outcome. (Figure 2). Paired pre and post-operative cuff data were obtained for 55 subjects (76%). Comparison of individual nomogram positions showed that all men diagnosed as BOO pre-operatively moved to an unobstructed point on the nomogram following TURP. All men classified as not obstructed pre-operatively remained so following surgery. Most patients in the equivocal groups became unobstructed (14/24, 58%) but three patients from that group moved into the obstructed category with 7 remaining equivocal. (Figure 3). Interpretation of results Analysis of interim data from this ongoing prospective study suggests that pre-operative urodynamic diagnostic categoristation using non-invasive parameters measured during the penile cuff test can be used to give improved prediction of good outcome from TURP. The test is simple and reliable for standard clinic use. The test is particularly useful for the 59% of men who can be confidently diagnosed as being obstructed or unobstructed but some men in the equivocal regions of the nomogram may require further urodynamic assessment for categorisation. Concluding message These initial data confirm that use of a nomogram plot of non-invasive pressure-flow parameters shows promise for diagnostic categorisation and follow up of men with LUTS. Figure 1 The Non-invasive Nomogram Figure 2 Nomogram position pre-op according to outcome

Figure 3 Nomogram position post-op according to pre-operative classification

References

1. Outcome of Elective Prostatectomy BMJ 1989;299:762-7 2. The Results of Prostatectomy J Urol 1979;121:640-2 3. Non-Invasive Bladder Pressure: the case for using a modified ICS nomogram. Neurourol Urodyn 2003;22(5):367

FUNDING: ACTION MEDICAL RESEARCH


59 Robinson D1, Balmforth J1, Cardozo L1, Parsons M1

1. Kings College Hospital IS URETHRAL RESISTANCE A USEFUL MEASUREMENT? Hypothesis / aims of study Currently there is no test of urethral function which is diagnostic of urodynamic stress incontinence and videocystourethrography remains the investigation of choice. Urethral Pressure Profilometry (UPP), urethral sphincter volume (1) and valsalva leak point pressures (2) are recognised tests of urethral function although they are not diagnostic. More recently measurement of urethral retro-resistance pressure (URP) has been proposed as a new test of urethral function and may have a role in the diagnosis of urodynamic stress incontinence(3). The aim of this study was to examine the relationship between urethral sphincter function and urodynamic diagnosis to determine if analysis of urethral pressure may be used as a diagnostic tool. Study design, materials and methods Women were recruited prospectively from a tertiary referral urodynamic clinic. All complained of troublesome lower urinary tract symptoms and all underwent videocystourethrography including uroflowmetry, cystometry and pressure/flow voiding studies using a Laborie Aquarius urodynamic system. Analysis of the urodynamic trace was performed and opening and closing detrusor pressure marked. These were defined as the detrusor pressure when flow begins and finishes respectively. In addition acceleration and deceleration of flow was calculated for the pressure flow study. All procedures were performed in accordance with ICS Guidelines for Good Urodynamic Practice. Statistical analysis was performed using SPSS (Version 10). Means were compared using the independent samples t test whilst correlation was performed using the Pearson method. Results In total 100 women were recruited to the study over a three month period. The urodynamic diagnoses are shown below [Table 1] Urodynamic Diagnosis Number Normal [Norm] 30 Urodynamic Stress incontinence [USI] 22 Detrusor Overactivity and Urethral Sphincter Incompetence [Mixed] 9 Detrusor Overactivity [DO] 29 Voiding Difficulties [VD] 9 Sensory Urgency [SU] 1 Table1: Urodynamic Diagnosis Mean opening and closing detrusor pressures with 95% confidence intervals are shown below grouped by urodynamic diagnosis: [Figure 1]

182892230N =

DIAGNOSIS

SUVDDOMixedUSINormal

95%

CI O

PE

NIN

G P

RE

SS

UR

E

50

40

30

20

10172491828N =

DIAGNOSIS

SUVDDOMixedUSINorm

95%

CI C

LOS

ING

PR

ES

SU

RE

70

60

50

40

30

20

10

0

FIGURE 1: OPENING (LEFT) AND CLOSING (RIGHT) PRESSURES BY DIAGNOSIS


There was wide overlap between diagnostic groups and neither mean opening, or mean closing detrusor pressure was found to be statistically significant between diagnostic groups. [Table 2]. In addition there was no statistically significant difference in mean acceleration and deceleration of flow between the groups studied and no significant correlation between acceleration of flow and opening pressure (p=0.269) and deceleration of flow and closing pressure (p=0.342). Diagnosis Mean Open

[mmHg] Mean Close [mmHg]

Mean Accel [mls/s2 ]

Mean Decel [mls/s2 ]

NORMAL 29.43 28.10 2.56 1.22 USI 24.31 22.61 3.39 2.07 Mixed 31.22 39.11 2.69 1.91 DO 29.75 32.25 3.08 1.44 VD 26.63 23.14 2.97 2.07 TABLE 2: MEAN DETRUSOR PRESSURES AND ACCELERATION/DECELERATION OF FLOW Interpretation of results Whilst this study has not directly measured urethral resistance it does provide evidence that assessment of urethral function by measuring urethral opening and closing pressures is neither diagnostic nor discrimatory. Furthermore there would appear to be no correlation between opening and closing detrusor pressures with acceleration/deceleration of flow rates. Concluding message These findings would suggest that measurement of urethral resistance alone may not be adequate to make a firm diagnosis of lower urinary tract symptoms. References

1. Neurourol Urodyn 1996; 15: 339-340 2. Curr Urol Rep 2001; 2(5): 388-391 3. Neurourol Urodyn 2004; 23(2): 109-114

60 Hashim H1, Abrams P1

1. Bristol Urological Institute DO SYMPTOMS OF OVERACTIVE BLADDER PREDICT URODYNAMICS DETRUSOR OVERACTIVITY? Hypothesis / aims of study The standardisation subcommittee of the International Continence Society (ICS) in its latest report in February 2002 defined overactive bladder (OAB) syndrome as urgency, with or without urge incontinence, usually with frequency and nocturia, if there is no proven infection or other obvious pathology. These symptom combinations are suggestive of urodynamically demonstrable detrusor overactivity (DO) but can be due to other forms of urethro-vesical dysfunction. DO is a urodynamic observation characterised by involuntary detrusor contractions during the filling phase which may be spontaneous or provoked. (ICS 2002) A previous study in male patients showed that 75% of patients with urge incontinence but only 44% of those with frequency and urgency had DO (1). In another study of female patients, 54.2% of patients with symptoms of OAB had DO (2). These studies were conducted before the new ICS report was published and thus may have been based on older definitions of urgency (strong desire to void accompanied by fear of leakage or fear of pain) and urge urinary incontinence (involuntary loss of urine associated with a strong desire to void). According to the new definition, symptoms of OAB are suggestive of DO, however the definition does not specify the actual correlation between OAB and DO. Based on clinical experiences, the aim of this paper is to define how well symptoms of overactive bladder syndrome predict urodynamic DO.


Study design, materials and methods All urodynamics (UDS) were conducted in a specialist referral centre performing about 20-25 UDS tests per week. This includes male and female children and adults undergoing standard, video and ambulatory UDS. The machines used include LectroMed and Dantec. Either an 8Fr filling catheter and epidural catheter, to measure vesical pressure (pves), or 6Fr double-lumen catheter was used. All the information from UDS including the medical history and examination was entered during the test onto a medical database. For the purposes of this study, the UDS database had to be converted into an easily accessible format (MS Access). All UDS investigations were done according to the ICS good urodynamics practices protocol (3) and all the investigators have obtained a certificate in UDS. The inclusion criteria were male and female adults (≥18 years old) with at least one symptom of OAB (urgency (U); urinary urge incontinence (UUI); frequency (F)), from February 2002 to February 2004. Nocturia was not included in the analysis. We then looked to see if these patients had DO or not. Patients who reported only UUI and no U where assumed to have urgency by definition. Patients with F alone (≥ 7 voids during the daytime) were not considered to have OAB. Results 1809 patients had urodynamics in that period. 1452 (80%) of those had complete storage symptom data entries. The others had one or more missing data on the database and thus were excluded. Of the 1452 patients, 1074 had symptoms of OAB and 378 had no symptoms of OAB. Table 1 summarises the results of all the patients with storage symptoms and those with storage symptoms and UDS DO. Table 2 summarises the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of UDS in patients with storage symptoms. Table 1.

No. of patients with

No. of patients with

% of patients with DO and symptoms

storage symptoms DO and symptoms

SYMPTOMS Male Female

Total Male Female Total Male Female Overall

No symptoms 57 128 185 22 40 62 38.6 31.25 33.5 F only 48 145 193 30 46 76 62.5 31.7 39.4 Total without OAB 105 273 378 52 86 138 59.5 31.5 36.5 U only 42 25 67 29 11 40 69.05 44 59.7 U&UUI 36 232 268 33 134 167 91.67 57.76 62.31 U&F 78 64 142 56 30 86 71.79 46.86 60.56 U&F&UUI 128 469 597 105 286 391 82.03 60.98 65.49 Total with OAB 284 790 1074 223 461 684 78.52 58.35 63.69 TOTAL 389 1063 1452 275 547 822 70.7 51.5 56.6

Table 2. Sensitivity Specificity PPV NPV 0.64 0.62 0.83 0.38 Interpretation of results The results show that 92% of men with U&UUI alone and 82% with U&F&UUI will have DO. This is not a significant difference (p=0.2). UUI in men seems to increase the probability that they will have DO. This is true for women as well, however the results are not as high as the men. In both men and women, having U&F does not seem to differ from having U alone in terms of predicting DO. In women, having U&F&UUI has the highest sensitivity in predicting DO. The possible reason for this is that women can experience both stress incontinence and UUI (mixed incontinence) making it difficult to differentiate the two while men rarely experience stress incontinence. In fact, 202 of the 232 women who had symptoms of U&UUI also had symptoms of stress incontinence. Also 71 of the 134 women who had DO and U&UUI also had UDS stress incontinence. Frequency alone is a poor predictor of DO (39%) in patients with OAB but better in men (62%) than women (32%). Overall, 83% of patients with DO have symptoms of OAB (PPV) and 64% of patients with OAB have DO (sensitivity).


Concluding message This study is the first one to look at the correlation between the symptoms of OAB and UDS DO since the publication of the new definition of OAB. It is also the first to involve both men and women.The definition of OAB is the best we have at the present time in predicting patients with DO. It seems to be a better predictor in men than in women. The more symptoms there are in women the better the correlation however in men the presence of urgency with urge incontinence alone can predict DO in about 92% of cases. 78.5% of men and 58.4% of women with OAB will have DO. This is mainly due to the presence of stress incontinence and sphincter weakness in women. From a clinical and practical point of view, the most important thing before UDS is to enquire about and treat the patient’s most bothersome symptom. UDS should be done only if it is going to change management. References 1. Detrusor instability in men: correlation of lower urinary tract symptoms with urodynamic findings. J Urol. Aug 2001;

166: 550-553. 2. Overactive bladder symptoms: do we need urodynamics? Neurourol Urodynam. 2003; 22 (2): 105-108. 3. Good urodynamic practices: uroflowmetry, filling cystometry and pressure flow studies. Neurourol Urodynam. 2002;

21: 261-274. 61 Lewis J1, Sullivan M1, Nabha K1, Bartolome V1, Siroky M1, Yalla S 11. VA Boston Healthcare System RELATIONSHIPS BETWEEN BLADDER OUTLET OBSTRUCTION, BLADDER COMPLIANCE AND RENAL FUNCTION IN ADULT MEN WITH LUTS Hypothesis / aims of study Benign prostatic hyperplasia (BPH), with or without bladder outlet obstruction (BOO), is known to be a major contributor to patient complaints of lower urinary tract symptoms (LUTS). What is unclear, however, is whether LUTS, if caused by BOO, merely affects quality of life rather than altering bladder compliance and/or renal function. While it is well-established in children as well as adults with neurogenic bladder dysfunction that poor bladder compliance results in upper tract deterioration, this relationship has not been clearly demonstrated in adult men with BPH. A previous study suggested that in a small subset of men with diminished bladder compliance, who have both BOO (diagnosed by voiding profilometry) and detrusor instability (DI), there is a significant increase in the incidence of azotemia [1]. As for the causes of diminished bladder compliance in the BPH population, factors such as advanced age, BOO, high voiding pressures, and DI have been implicated [2]. To extend our understanding of the relationships between bladder compliance, outlet resistance and renal function associated with non-neuropathic voiding dysfunction presumably related to BPH, we analyzed a group of veterans with bothersome LUTS. Study design, materials and methods A retrospective analysis was carried out in 99 veterans who presented to the Urology clinic complaining of LUTS and underwent a pressure-flow urodynamic study (UDS). Patients with spinal cord injury, multiple sclerosis, Parkinson's disease or other overt neurogenic causes of voiding symptoms were excluded. Bladder outlet obstruction index (BOOI), capacity and work parameters were calculated from the UDS. Bladder contractility was assessed using the maximum Watts factor (Wf). Bladder compliance was calculated from the cystometry curve prior to the onset of bladder contraction, and end-fill compliance was calculated over the final 50 ml of bladder filling. Serum measures of BUN and creatinine were collected. Note was made as to whether the patient had concurrent hypertension (HTN), diabetes mellitus (DM), and/or congestive heart failure (CHF). Results Mean age of the patient group was 66.8 years (range: 37-86). BOOI showed no significant correlation with either total or end-fill compliance, BUN or creatinine but was moderately correlated with internal work (r=0.37, p<0.05). Compliance was weakly correlated with external work (r=0.28, p=0.005) and BUN (r=-0.28, p=0.005) but not correlated with Wf or internal work. Age was significantly correlated with BUN (r = 0.375, p<0.001) and creatinine (r=0.29, p=0.005). Patients with poor compliance (<30 ml/cmH2O) showed no significant difference


in BUN and creatinine or degree of obstruction compared to patients with normal compliance. Furthermore, subgroups based on severity of obstruction (BOOI<20, BOOI 20-40, BOOI>40) showed no significant differences in compliance (mean compliance ∀ SEM = 59 ∀ 8.0, 39 ∀ 6.5, and 44 ∀ 4.5 ml/cmH2O respectively), BUN or creatinine. The incidence of diminished compliance was similar (43%) in both the obstructed and non-obstructed patients. 18.9% (n=18) had decreased renal function (serum creatinine = 1.3 mg/dl); however, compliance, degree of obstruction, and age in these patients were not different from patients with normal renal function. Although the incidence of hypertension was the same in both

groups, the incidences of DM (50%) and CHF (11.1%) were higher (but not significantly) in patients with decreased renal function compared to those with normal renal function (27.3% and 5.2%). DM, HTN or CHF were present in 31.6%, 61.1% and 6.3% of patients respectively. No differences in serum measures of renal function, compliance and BOOI were detected compared respectively with those without these diseases. 31.6% of the cohort had none of these comorbidities. In patients with both HTN and DM, renal function in those with BOO (37%) was not different from those without BOO. Interpretation of results While LUTS due to BOO can be bothersome to a man’s quality of life, the degree of obstruction is not associated with a decline of his bladder compliance or of his renal function. The incidence of diminished compliance is similar in patients with and without obstruction suggesting that changes in compliance are not exclusively attributable to an obstructive process in patients with LUTS. Renal function is not significantly reduced in this patient population, despite 61% being significantly obstructed. Changes in BUN are associated with changes in age and compliance but are unrelated to severity of obstruction. The lack of significant renal deterioration in this population is consistent with a recent study that showed no cases of renal insufficiency in 3047 BPH patients followed over 5 years [3]. Comorbidities (DM, HTN) do not appear to significantly impact renal function in this cohort, even when associated with BOO. Concluding message Since diminished bladder compliance and deterioration of renal function are not uniquely associated with BOO, it is unclear why a few isolated patients develop severe deterioration of the upper tract, compromising renal function. We speculate, however, that either the duration and rapidity of progression of BOO, diminished proprioception of bladder filling induced by covert neuropathic changes, bladder ischemia and/or age-related changes in the bladder smooth muscle may be responsible for deleterious upper tract changes and renal compromise in select patients. These aspects require future investigation. References 1. Urodynamic risk factors for renal dysfunction in men with obstructive and nonobstructive voiding dysfunction. J Urol;

1997; 181-185. 2. Interrelationships of bladder compliance with age, detrusor instability, and obstruction in elderly men with lower urinary

tract symptoms. Neurourol Urodynam 1999;18:3-15. 3. The long-term effect of doxazosin, finasteride, and combination therapy on the clinical progression of benign prostatic

hyperplasia. N Engl J Med 2003; 249 (25):2387-2398. FUNDING: Department of Veterans Affairs, Medical Research Service, Washington, D.C.


62 Biscotto S1, Costantini E1, Rociola W1, Mearini L1, Bini V2, Porena M1

1. Urology Dept, 2. Pediatrics Dept CUT-OFF VALUES TO DEFINE BLADDER OUTLET OBSTRUCTION (BOO) IN WOMEN Hypothesis / aims of study Diagnosing BOO in women is arduous. Symptoms, clinical examination, free uroflowmetry, radiographic and endoscopic findings do not establish a definitive diagnosis and the results of the pressure flow study may be difficult to interpret because of several criteria without any unanimous consensus. The aim of this study is to define cut-off values in urodynamic parameters which will serve to identify female BOO. Study design, materials and methods We studied 780 consecutive female patients, using our standard urogynaecological protocol which includes: case history, symptoms questionnaire, uro-gynaecological and neurological examination, dynamic ultrasonography, urodynamic and/or videourodynamic tests. Exclusion criteria were recurrent lower UTI, bladder stones or tumours, suspected neuropathy, complete urinary retention and incomplete or non-evaluable pressure/flow study (i.e. no micturition during the test). All patients underwent urodynamic tests according to ICS criteria. Patients with abdominal straining (arbitrarily defined as abdominal pressure over 10 cm H2O) during voiding were excluded to prevent abdominal straining-related artefacts in the analysis of P/F curves. The patients were divided into two groups “obstructed” (n= 65) which included women with severe obstructive symptoms and major descensus (Cystocele > grade 2) and “controls” (n=101) who had no signs or symptoms of obstruction, no previous history of pelvic surgery for incontinence, no descensus (cystocele, urethrocele, rectocele or uterus prolapse), no urethral pathology as shown by clinical examination and ultrasound findings. Statistical analysis was based on the following parameters: Qmax during free uroflowmetry; pdetQmax, Qmax and Uretral Efficency at Qmax (UEQmax) of PUMA in P/F study. ROC curves to determine the optimal cut-off values were used. Sensitivity and specificity were calculated for different cut-off values. The Agreement Kappa test was used to assess the capacity of the different methods (Chassagne, Lemak, Romanzi, Blavais) (1) to classify obstructed patients correctly. Results In the “controls” ( 101 patients, mean age 55.9±10.3) the mean Qmax free was 27.8±12.5 ml/s (median 26.5 ml/s; interquartile range (IR) 18 to 37 ml/s), the mean pdetQmax was 19.7±9.9 cmH2O (median 16 cmH2O; IR 12-28.5 cmH2O), the mean Qmax in P/F study was 22.3±7.8 ml/s (median 21.2 ml/s; IR 17.3 - 27.2 ml/s) , the mean UEQmax was 99.2±40.5 (median 87; IR 74 -124). In the “obstructed ” group (65 patients, mean age 62.5±10.5) the mean Qmax free was 16.4±9.1 ml/s (median 12.8 ml/s; IR 10-20.3 ml/s), the mean pdetQmax was 33.8±17.8 cm H2O (median 30 cmH2O; IR 20.5-45 cmH2O), the mean Qmax in P/F study was11.2±6.9 ml/s (median 9 ml/s; IR 5.9-16 ml/s) , the mean UEQmax was 49.5± 32.5 (median 37; IR 26-69). Significant differences emerged in the two groups for Qmax free (p<0.0001), pdetQmax (p< 0.0001), Qmax in P/f study (p<0.0001) and UEQmax (p<0.0001). In the absence of a well-defined gold standard for obstruction, clinical symptoms and severe cystocele were used as surrogate gold standard to construct the ROC curves (figs 1,2,3,4). For Qmax free , the area under the curve (AUC) was 0.78 (SE 0.04). In an attempt to balance sensitivity and specificity, the best peak free flow rate cut-off was 21.15 ml/s (sensitivity 81.6%, specificity 64.1%). For pdetQmax the AUC was 0.76 (SE 0.04), the best value was 23.5 cm H20 (sensitivity 68.8%, specificity 66.7%). For Qmax in P/Fstudy the AUC was 0.87 (SE 0.03), the best value was 16.5 ml/s (sensitivity 79.7%, specificity 79.2%). For UEQmax the AUC was 0.86 (SE 0.03), the best value was 70.5 (sensitivity 78.1%, specificity 77.1%). When pdetQmax and Qmax were considered together (pdetQmax - 2* Qmax) as in the P/Fstudy in men (2) the AUC was 0.86 (SE 0.03), the best value was –11.5 (sensitivity 78.5%, specificity 75.0%) (Fig. 5). The Agreement Kappa test showed the BOO classification capacity of the different methods as: Chassagne K= 0.53, Lemack K=0.49, Romanzi K=0.46 and Blavais K=0.19. Interpretation of results In our study different cut-off values of urodynamic parameters were obtained from ROC curves for BOO in women. Qmax free was most unbalanced in specificity and sensitivity.When it is < 21.15 ml/s the probability of BOO is very high. The pdetQmax curve had the lowest specificity and sensitivity. The Qmax curve in the P/F study, UE and pdetQmax - 2* Qmax all had the same areas under their curves (AUC) and overlapping specificity and sensitivity values. The BOO classification capacity was moderate for the Chassaigne, Lemack and Romanzi methods and poor for the Blaivas method.


Concluding message The additional parameters provided by the PUMA method of analysis offer some advantage (detrusor contractility and pathology-related curves) (3) over the other urodynamic parameters (in P/F study: pdetQmax > 23.5 cm H2O; Qmax < 16.5 ml/s; pdetQmax - 2* Qmax >-11.5) which do, however, detect BOO in women satisfactorily . References 1) Neurourol Urodyn 19:533, 2000 2) Neurourol Urodyn 16:1-18, 1997 3) Neurourol Urodyn 22:206-222, 2003

Qmax free

1 - Specificity

1,00,75,50,250,00

Sens

itivi

ty

1,00

,75

,50

,25

0,00

PdetQmax

1 - Specificity

1,00,75,50,250,00

Sens

itivi

ty

1,00

,75

,50

,25

0,00

Qmax in P/F study

1 - Specificity

1,00,75,50,250,00

Sens

itivi

ty

1,00

,75

,50

,25

0,00

Fig. 1 Fig. 2 Fig. 3

UE Qmax

1 - Specificity

1,00,75,50,250,00

Sens

itivi

ty

1,00

,75

,50

,25

0,00

PdetQmax-2*Qmax

1 - Specificity

1,00,75,50,250,00

Sens

itivi

ty

1,00

,75

,50

,25

0,00

Fig. 4 Fig. 5

63 Williams K1, Martin J2, Abrams K1, Assassa R P3, Chapple C4, Shaw C 5, Turner D1, Sutton A1, Cheater F6 1. University of Leicester, 2. University of Nottingham, 3. Pinderfields and Pontefract Hospital, 4. Royal Hallamshire Hospital, 5. University of Cardiff, 6. University of Leeds SYSTEMATIC REVIEW AND EVALUATION OF METHODS OF DIAGNOSTIC ASSESSMENT FOR URINARY INCONTINENCE. Hypothesis / aims of study The evidence available on the accuracy, acceptability and cost (both financial and personal) of diagnostic assessment methods for urinary incontinence is inconsistent. This project aimed to: identify the literature on methods of diagnostic assessment, evaluate the quality of the evidence, evaluate the clinical efficiency of alternative diagnostic assessment methods and estimate the cost per case correctly diagnosed. Study design, materials and methods The review followed the NHS Centre for Review and Dissemination guidelines to identify, appraise and summarise the published evidence on methods of diagnostic assessment (1). Online bibliographic databases (Medline, EMBase and Cinahl) were searched using the standard search filter for diagnostic studies from 1966 to the end of 2002 resulting in a total of 6009 individual papers. Exclusion criteria were: diagnosis in children, reports in a non-English language, case reports, letters, reviews and papers investigating interventions where


diagnostic tests were used as outcome measures. All identified papers were assessed for relevance by the first investigator on the basis of abstract, or if not available, title only. A proportion were then read by the second investigator. Any discrepancies were discussed. The QUADAS (2) tool was used to assess the included studies for quality with 7 different investigators assessing approximately thirty papers each. Results After application of inclusion and exclusion criteria 197 papers were found to be relevant and included in the review. Studies which reported the results of applying the same diagnostic procedure using the same threshold value were pooled using a fixed effects meta-analysis model in order to produce pooled estimates of sensitivity and specificity together with 95% Confidence Intervals (CI). Generally, reporting in the primary studies was poor and there was a lack of literature in the key clinical areas. Only a limited number of studies could be combined or synthesised. Table one shows the pooled sensitivities and specificities of commonly used primary care tests compared to multi-channel urodynamics. Table 1. Primary care tests versus multi-channel urodynamics Test Number of studies Sensitivity Specificity Clinical History (USI) 15 0.92 (95% CI 0.90-0.95) 0.56 (95% CI 0.48-0.64) Clinical History (DO) 8 0.56 (95% CI 0.44-0.72) 0.88 (95% CI 0.83-0.93) Scales (USI) 2 0.88 (95% CI 0.71-0.96) 0.60 (95% CI 0.52-0.68) Diary (DO) 1 0.88 (95% CI 0.71-0.96) 0.83 (95% CI 0.77-0.87) We examined the incremental cost effectiveness of three primary care tests used in addition to history (scales, diary and pad test) and found the diary had the lowest cost-effectiveness ratio of between 42 euros (£28) and 97 euros (£65) per extra unit of effectiveness (or case diagnosed). Tests performed in secondary care were also combined where possible and showed that imaging by ultrasound to determine leakage was found to be effective in the diagnosis of USI in women with a sensitivity of 0.94 and specificity of 0.83 and the supine clinical stress test for USI in women was found to have a sensitivity of 0.88 and specificity of 0.84. Interpretation of results This is the first systematic review of methods for diagnosing urinary incontinence. Reporting in primary studies was poor, clinical interpretation was often difficult because few studies could be synthesised and conclusions made. However, evidence suggests that a large proportion of women with USI can be correctly identified in primary care from history alone, although women with DO may fail to be identified from history alone. In secondary care ultrasound imaging and the stress test may offer valuable alternatives to urodynamic investigation. Concluding message The diary appears to be the most cost-effective of the primary care tests (diary, pad test and validated scales) used in addition to clinical history. Further primary studies adhering to STARD (3) guidelines are required on commonly-used tests. References 1. Undertaking systematic reviews on research of effectiveness. CRD guidelines for those carrying out and

commissioning reviews. CRD Report Number 4 York: NHS Reviews and Dissemination, 2001:1-50 2. The development and validation of methods for assessing the quality and reporting of diagnostic studies. Health

Technology Assessment 2004. http://www.ncchta.org/project. 3. The STARD statement for reporting studies of diagnostic accuracy: explanation and elaboration. Clin Chem. 2003

Jan;49(1):7-18. FUNDING: Health Technology Assessment Programme, Department of Health, UK


64 Claerhout F1, De Ridder D1, Verbeken E2, Deprest J1

1. Pelvic Floor Unit, University Hospitals Leuven, 2. Department of Pathology, University Hospitals Leuven A LONGITUDINAL MORPHOLOGICAL EVALUATION OF THE HOST RESPONSE TO TWO COLLAGEN BASED AND ONE POLYPROPYLENE IMPLANTS IN A RABBIT MODEL FOR ABDOMINAL WALL HERNIA. Hypothesis / aims of study Fascial reconstruction of prolapsed pelvic organs using native tissue can be reinforced with implant materials to prevent or treat recurrence. Biomaterials may overcome the side effects related to the use of non-absorbable implants such as erosion, dyspareunia and infection. Xenografts are increasingly used but little is known about their long term durability. We conducted a long term experimental study comparing the integration of cross-linked porcine dermal collagen (Pelvicol,Bard), collagen matrix derived from small intestinal submucosa (SIS-4L,Cook) and Prolene (Johnson&Johnson) in a rabbit model for abdominal wall hernia repair. Study design, materials and methods Four 2.5x2.5cm full thickness abdominal wall defects were created in 45 New Zealand rabbits. In a random fashion the defects were closed with one of the studied materials. Nine rabbits were sacrificed at either 30,60,90,180 or 365 days(d). Explants were fixed, embedded and 5µm sections were stained for morphological evaluation. Representative areas of the implant, as well as the interface between the implant and recipient’s native fascia were assessed with a semi-quantitative scale (Badylak,2002) documenting the inflammatory response, neovascularisation (Hematoxylin and Eosin) and the connective tissue deposition (Movat). Immunohistochemistry was performed to document the presence of macrophages (RAM-11; Dako) and collagen deposition. Results and interpretation of results: Structural integrity: Prolene implants remained intact the entire observation. SIS-4L implants were not more recognisable from 60d onwards. In the Pelvicol group there were important interindividual differences. Up to 180d the implants remained unchanged but at one year half of the implants were degraded in places; the other half of the implants remaining entirely intact. Inflammatory response: all materials induced a pronounced inflammatory reaction at 30d, declining over time (Fig.1). At 30d, the infiltrate in collagen materials included mononuclear and polymorphonuclear cells while in the Prolene group the infiltrate was dominated by mononuclear cells. Later on, Prolene was associated with the strongest inflammation, persisting till the end of the experiment. The inflammatory response to collagen materials weakened earlier in time to persist at low levels for SIS. At all times, Prolene and SIS-4L implants had inflammatory cells within the implant. In Pelvicol the infiltrate remained limited to the interface but from 180d onwards, in half of the Pelvicols an infiltrate was seen within the implant without signs of suppurative infection, whereas others did not. Collagen deposition (Fig.2): Prolene induced an intermediately dense collagen deposition appearing irregularly organised, it’s amount showing no significant changes over time. However the nature of the connective tissue went from cellular to more fibrous and organised. Compared to Prolene, the amount of collagen deposited around SIS-4L implants was comparable early on, however the new collagen was more orderly organised. At 365d the area of remodelling appeared as a thin layer of fibrous collagen, macroscopically almost transparent. In Pelvicol, the collagen deposition started off at lower levels to increase slowly over time ending at similar levels as the above after one year. Up to 90 d the connective tissue sandwiched the implant without invading it. From 180 days on there was a progressive connective tissue invasion in half of the implants; the other half remaining intact without any sign of connective tissue invasion. Neovascularization: Prolene induced the strongest neovascularisation (Fig.3)(4-10 blood vessels/HPF) in in the first 60d. Afterwards the score did not change anymore, but the vessel calibre increased. In the SIS-4L group newly generated blood vessles looked smaller in calibre. In Pelvicol implants the newly generated blood vessels initially could only be found at the interface, to extend only later on to the centre of the implant Concluding message: The host response to Prolene is clearly different from that to collagen based materials, but also between the cross-linked and non-cross-linked materials. Prolene remains intact and induces a strong acute inflammatory


response evolving into a persisting chronical inflammation. It gets colonized by a rather disorganised connective tissue. The original SIS-4L collagen matrix is degraded within 60d after inducing a strong acute inflammatory response. The material is rapidly replaced by architecturally well organised collagen, the total amount not increasing over time. Pelvicol remains almost unaffected the first half year, with inflammatory cells not invading the implant and collagen deposition paralleling the implant. At one year half of the Pelvicol implants shows areas of local degradation. Histologically this correlates to an infiltrate by inflammatory cells, and partial replacement with newly formed connective tissue. The other half of the implants remained quasi intact. We have so far no explanation why this would happen in only half of the animals.

30 60 90 180 3650

1

2

3

ProlenePelvicolSurgsis

ns *° ° ns *#

Time groups (days)

Mon

onuc

lear

cel

ls

*p < 0.05 Prolene versus Pelvicol, °p < 0.05 Proleneversus Surgisis, # p < 0.05 Pelvicol versus Surgisis

Mononuclear cells

30 60 90 180 3650

1

2

3ProlenePelvicolSurgisis

*# *# °# ns *°

*p < 0.05 Prolene versus Pelvicol, °p < 0.05 Prolene versus Surgisis, # p < 0.05 Pelvicol versus Surgisis

Time group(days)

Am

ount

Amount of collagen

Neovascularsation

30.0 60.0 90.0 180.0 365.00

1

2

3ProlenePelvicolSurgisis

*° *° ns ns ns

Time group (days)

vasc

ular

ity

*p < 0.05 Prolene versus Pelvicol, °p < 0.05 Proleneversus Surgisis, # p < 0.05 Pelvicol versus Surgisis

Fig 1. Fig 2. Fig 3. References: Badylak SF et al. Morphologic study of small intestinal submucosa as a body wall repair device. J Surg Research 2002;103:190-202. 65 Barry C L1, Dietz H P2, Rane A1, Wilson P D3

1. James Cook University, Australia, 2. Royal Prince Alfred Hospital, Sydney, Australia, 3. Dunedin Medical School, University of Otago, New Zealand IS THE COUGH TEST NECESSARY? A CASE CONTROL SERIES OF TWO TECHNIQUES OF TVT ADJUSTMENT Hypothesis / aims of studyThe Tension- free vaginal tape (TVT, Gynecare) is probably the most successful new anti- incontinence procedure of the last decade. The original technique (1,2) relies on a cough test in the conscious patient to adjust sling tension. Competitor implants and techniques do not consistently use this technique and seem to result in good success rates. In this case control series of patients after TVT implantation, the authors compared two adjustment techniques. One surgeon used a technique without the cough test (Group A), leaving enough space between implant and urethra to pass Metzenbaum scissors at rest, the other utilized the cough stress test (Group B) as in the originally described technique. Study design, materials and methods Patients after TVT surgery performed by one of the two authors (Group A, Surgeon 1, Group B, Surgeon 2) were invited for review in the context of external postoperative audits conducted by the first author. Follow- up appointments consisted of a standardized interview, free flowmetry and translabial ultrasound for estimation of residual urine, position and mobility of tape and bladder neck relative to the inferoposterior margin of the symphysis pubis (3). The ultrasound technique has recently been shown to have good interobserver repeatability (%CV of 0.08 to 0.26 for tape position and %CV of 0.12 for total tape mobility) (3). Matching was undertaken for age, preexisting urge incontinence, preoperative maximum flow rate centile, concomitant anterior repair and length of followup.

Parameter Group A (n=54) Group B (n= 52) P Age 57.8 (12.3) 58.2 (13.3) n.s. Preexisting Urge Incontinence 38/ 53 40/ 52 n.s. Preoperative MFR Centile 25.6 (23.6) 36.2 (31.2) n.s. Concomitant Anterior Repair 17/54 13/52 n.s. Length of followup 0.74 (0.32) 0.65 (0.23) n.s.

Table 1: Results of matching


Results 54 women in Group A were compared to 52 women in Group B. Matching resulted in well balanced groups. There were no significant differences between groups for subjective cure (77% in Group A vs. 83% in Group B), satisfaction rate (83% vs. 84%), subjective symptoms of stress (20% vs. 19%) or urge incontinence (63% vs. 64%), frequency and nocturia. There were less symptoms of voiding dysfunction overall in Group A (46% vs. 69%, p= 0.019); see Table 2 for a breakdown of symptoms. The incidence of recurrent urinary tract infection was similar in both groups. Parameter Group A (n=54) Group B (n= 52) P Hesitancy 6/54 13/52 0.062 Poor Stream 13/54 32/52 0.028 Stop- start voiding 8/54 18/52 0.018 Straining to void 3/54 4/52 n.s. Incomplete emptying 11/54 20/52 0.041 Table 2: Symptoms of voiding dysfunction, X2 test. Postoperative free flowmetry indices did not differ significantly. In both groups there was a reduction in maximum flow rate centiles (MFR centiles), and although this was more marked in Group B (-17.3 vs. -13.1 centile points), this difference was not significant. Data on residual urine was incomplete and therefore not analyzed. Table 3 gives parameters of tape position and mobility which differed markedly. Parameter Group A (n=54) Group B (n= 52) P x-r 1.10 (SD .59) .72 (SD .73) 0.005 y-r 1.67 (SD .36) 1.63 (SD .36) n.s. x-s -.69 (SD .47) -.47 (SD .59) 0.038 y-s .83 (SD .58) .81 (SD .54) n.s. tape mobility 2.04 (SD .64) 1.56 (SD .65) < 0.001 Table 3: TVT position and mobility on ultrasound (2-sample T test). X-r, y-r: vertical and horizontal distance between tape and inferoposterior symphyseal margin at rest, x-s and y-s, same parameters on Valsalva. Tape mobility: difference between positions at rest and on Valsalva. Interpretation of results This case control study of two methods of tape adjustment implies that using a cough test for tape adjustment during TVT insertion may result in unnecessary tightening of the tape. Avoiding the cough test and placing the TVT more loosely than originally described seems to have no negative effect on patient satisfaction or subjective symptoms of stress incontinence. There may even be a benefit in terms of reducing symptoms of voiding dysfunction although free flowmetry parameters did not vary significantly in this study. The difference in individual technique between these two single surgeon series was clearly evident on ultrasound imaging, with parameters of tape position and mobility showing an implant that was more mobile on Valsalva in the group without cough test. Concluding message Individual variations in technique such as the use of the cough stress test for tape adjustment may have a significant impact on symptoms and tape position and mobility. However, success rates and patient satisfaction do not seem to be greatly affected, a finding that again emphasizes the wide range of clinical safety and efficacy of modern suburethral slings. References

1. Acta Obstet.Gynecol.Scand.Suppl. 1998;168:34-37. 2. Int.Urogynecol.J.Pelvic.Floor.Dysfunct. 1996;7:81-5 3. Am. J. Obstet. Gynecol. 2003;188:950-53


66 Pifarotti P1, Meschia M2, Gattei U3, Bernasconi F4, Magatti F5, Viganò R6

1. Dept.Obs.Gyn,University Of Milan, 2. Dept. Obs.Gyn, Magenta, 3. Dept. Obs.Gyn, University Of Milan, 4. Dept. Obstet.Gynecol,Desio, 5. Dept. Obs.Gyn,Como, 6. Dept. Obs.Gyn, H S.Raffaele, Milano MULTICENTER RANDOMIZED TRIAL OF TENSION-FREE VAGINAL TAPE (TVT) AND INTRAVAGINAL SLINGPLASTY (IVS) FOR THE TREATMENT OF STRESS URINARY INCONTINENCE IN WOMEN Hypothesis / aims of study To compare the efficacy and morbidity of two mini-invasive procedure, TVT and IVS for the treatment of stress urinary incontinence in women with urethral hypermobility. Study design, materials and methods The study design was a prospective randomized multicenter trial involving four Italian hospitals. Patients with urodynamic proven stress urinary incontinence and urethral hypermobility were randomised to treatments according to a centralized computer-generated random list. On the assumption of 90% cure rate after TVT [1] it was calculated that 190 patients would be required (95 in each arm) to detect a clinically significant difference of 15% in cure rate between procedures with 80% power and an α level of 0,05. Patients enrolment began in January 2002 and had to be completed at the end of December 2002. Follow-up visits were scheduled after 3, 6, 12, 24 months from surgery. Exclusion criteria from the study were: age >75 years, previous anti-incontinence surgery, point Ba > -1, point C and Ap, Bp > than stage I, any coexistent pelvic pathology, urethral hypomobility (∆ Q-tip < 20°) and obesity (BMI > 30).The pre- and postoperative protocol included the following: a detailed urogynecologic history, grading the severity of stress incontinence by means of the Ingelman-Sundberg symptoms score, a physical examination, with the patient recumbent and straining down, to identify the presence of pelvic floor defects according to the POP-Q system classification, a cotton swab test to assess the mobility of the urethra, a 1-hour pad test, a stress test in the supine and standing positions with a comfortably filled bladder (300 ml) and a multichannel urodynamic evaluation including uroflowmetry, provocative cystometry and urethral profilometry. The primary outcome measure was rate of success for both the procedures. The secondary outcome measure was rate of complications observed. The postoperative evaluation included the collection of data regarding time required for surgery, type of anesthesia, intra and postoperative complications, time to resumption of spontaneous voiding, length of hospital stay and analysis of outcomes. The outcome of surgical treatment was estimated both subjectively and objectively. All patients were informed about the study and procedure and gave their informed consent. The Statistical Package fo Social Sciences was used for data analysis. Continuos data were reported as means + standard deviation (SD)and analysed with Student’s t test. Categoric relationship were analysed by the χ2 test with Yates’ correction or Fisher exact test, as appropriate. Probability values of < 0.05 were considered statiscally significant. Results From january 2002 and December 2002, 179 patients with stress urynary incontinence and urethral hypermobility were enrolled in the study. After random assignment 92 patients underwent the TVT procedure and 87 the IVS procedure. Patients had mean age of 56 + 10 years, BMI 26 + 3, and parity 1.7 + 1. All complained of stress urinary incontinence with 62 (35%) and 24 (13%) women also reporting symptoms of urgency and urge incontinence.The mean Q-tip value was 43° + 14° and the mean weight of pad test was 33 + 23 g. Most of women (64%) were operated on under local anesthesia and the mean time required for surgery was 27 + 7 min. There were no significant differences between the two groups with respect to any of these data and no differences were seen in urodynamic parameters. Intraoperative complications included 6 bladder perforations (3.3%) and the development of 4 retropubic hematomas (2.2%) that resolved spontaneously in 3 out of four patients. Resumption of spontaneous voiding was delayed in patients undergoing TVT when compared with those who received IVS (1.6 + 1.7 days vs 0.9 + 0.4, p = 0.02)) The median follow-up time for each group was 22 and 23 months respectively. Subjectively 80 (87%) of women in the TVT group were cured compared with 68 (78%) in the IVS group (p = 0.71). Objectively cure of stress incontinence was observed in 79 (86%) and 65 (75%) patients respectively (p =0.62). Postoperative complications included: voiding difficulties in 12 and 9 women respectively, recurrent UTI in 11 and 14 subjects


and vaginal erosions in 8 (9%) of the patients who underwent IVS procedure (p = 0.013), of whom 6 required surgical removal of the tape. Interpretation of results TVT and IVS are two different mini-invasive techniques sharing the objective to support the mid-urethra in a tension-free manner. The main difference between them is the framework of the prolene tape (monofilament vs multifilament) that could be responsible of different effects on urinary tract function. Our data show that both the procedures are effective for the treatment of stress urinary incontinence. Resumption of spontaneous voiding without significant residuals was delayed in women undergoinng TVT when compared with IVS, however we must take in account that 9% of women undergoing IVS showed vaginal erosions that required in most of them the surgical removal of the tape. Concluding message TVT and IVS are equally effective in the treatment of stress urinary incontinence References:

1. Meschia et al. Tension-free vaginal tape: analysis of outcomes and complications in 404 stress incontinent women. Int Urogynecol J 2001(Suppl.2):S24-S27

67 Lim Y N1, Rane A2, Barry C2, Corstiaans A3, Dietz H P4, Muller R 21.Gold Coast Hospital, 2.James Cook University, 3.Townsville Hospital, 4.Royal Hospital for Women THE SUBURETHRAL SLINGPLASTY EVALUATION STUDY IN NORTH QUEENSLAND (SUSPEND): A RANDOMIZED CONTROLLED TRIAL Hypothesis / aims of study To compare the safety and efficacy of 3 different types of suburethral slings (TVT, IVS and SPARC) for the treatment of urodynamic stress incontinence. Study design, materials and methods Following ethics approval and informed consent, 195 (3x65) patients with urodynamic stress incontinence were randomly assigned to undergo suburethral slingplasty with TVT (Johnson & Johnson), IVS (Tyco Healthcare), or SPARC (American Medical Systems). The subjects were blinded to the type of sling implanted. The suburethral slings were implanted with the method described by Ulmsten et al [1] with exception to the following: (1) most cases were performed under general anaesthesia and, (2) the cough test was not performed and a space wide enough to allow the passage of Metzenbaum scissors was left between the sling and the urethra. The main outcome measures were: (1) operative and short-term complications, (2) pre- and post-operative symptomatology and (3) pre- and post-operative urodynamic studies findings. Randomization proved to be successful in that the 3 groups of patients were comparable in terms of age, vaginal parity, menopausal status, past history of anti-incontinence or prolapse surgeries, mode of anesthesia, concomitant procedures and pre-operative urodynamic parameters. Results There was no significant difference between the incidence of urethral injury, bladder injury or prolonged catheterisation between the 3 groups. However, in the SPARC group there was a trend for urethral injury to occur more frequently (4.9% vs 0% & 0%; p=0.11), and also a statistically significant increased rate of sling protrusion (13.1% vs 3.3% & 1.7%; p=0.04) when compared to TVT and IVS. Subjectively, there was no significant difference between stress urinary incontinence cure rates (78.7%, 78.3%, 75.0%; for TVT, IVS and SPARC respectively; p=0.83), patient satisfaction rates (83.6%, 83.3%, 85.9%; p=0.99) or incidences of de novo urinary urgency (3.3%, 8.3%, 5.0%; p=0.90) and urge urinary incontinence (6.6%, 1.7%, 10.0%; p=0.06). In patients who underwent postoperative urodynamics studies (>90%), no significant differences in urodynamic stress incontinence cure rates (87.9%, 81.5%, 72.4%; p=0.11); incidences of de novo detrusor overactivity (3.4%, 3.7%, 1.7%; p=0.26) or dysfunctional voiding (5.2%, 3.7%, 6.9%; p=0.76) were observed. Patients in all 3 groups were found to have slight reductions of maximal and average urinary flow rates following suburethral slingplasty.


Interpretation of results The overall cure, as well as subjective outcomes, demonstrate a high success rate for all 3 slings. As the TVT and SPARC slings are very similar in vitro [2], we postulate that the increased incidence of sling protrusion and the trend for SPARC patients to have slightly lower objective cure rates to be related to the implantation method of the SPARC sling. Due to the elasticity of the TVT, when the plastic sheath is being removed after sling placement, there is a “pre-tensioning” effect that causes the tape to “spring” back up in a caudal direction. The tensioning suture of the SPARC sling limits this effect, and hence when placed with similar tension as the TVT, tended to become looser. With the IVS tapes which are much less elastic than TVT and SPARC slings, the surgeon would naturally leave it in a more “snug-fit” fashion under the urethra, and thus not become as loose as a SPARC sling. Although there was a trend for slight differences in overactive bladder symptoms between the 3 groups, the number of patients affected was small and the clinical significance is unclear. Otherwise, no significant differences could be observed between the monofilament (TVT, SPARC) and multifilament (IVS) slings. Concluding message All 3 slings are generally quite successful for the treatment of urodynamic stress incontinence. The SPARC tapes showed more sling protrusion complications, probably as a result of the insertion method used in this study. We recommend the cough test to be performed for SPARC sling placement to allow for more accurate sling tensioning. Reference:

1. An ambulatory surgical procedure under local anesthesia for treatment of female urinary incontinence. Int Urogynecol J 1996; 7:81-6

2. Mechanical properties of urogynecologic implant materials. Int Urogynecol J 2003; 14:239-43 68 Masata J1, Martan A1, Svabik K1, Drahoradova P1, Halaska M1, Pavlikova M2, Hlasenska J2

1. Department of Obstetrics and Gynecology, Charles University, Prague, 2. EuroMISE centre of the Charles University and Academy of Science, Prague, Czech Republic CHANGES OF THE LOWER URINARY TRACT AFTER SUCCESFUL TVT OPERATION – ULTRASOUND STUDY Hypothesis / aims of study Tension free vaginal tape (TVT) is a widely-used method for the treatment of stress urinary incontinence. To date there are no relevant data about the complex changes of the lower urinary tract after this procedure, although various studies of the mechanism of TVT have been published. The aim of our study was to evaluate changes of the lower urinary tract after succesful TVT operation (especially changes in the mobility of the whole urethra), to evaluate these changes in different mobility types, to evaluate the changes of the proximal urethra (funnelling) and of the thickness of the urinary bladder, and to evaluate the relationship between the position and mobility of tape and the mobility of the urethra. Study design, materials and methods This prospective study included 52 women with urodynamically proved stress urinary incontinence. Their mean age was 57.2 years (SD=11), mean BMI was 27.5 (SD=4.6), and mean parity was 1.9 (SD=0.6). An ultrasound examination was performed before TVT procedure and approximately 3-6 months after surgery. For the perineal examination a curved array probe 5 (3.5) MHz was used, and the introital examination was performed with sector probe 7 (5) MHz (Acuson 128 XP 10). Before the ultrasound examination the urinary bladder was filled to 300 ml with sterile saline. The measurements were taken in supine position at rest and during maximal Valsalva. Because the anatomical length of the urethra varies, measurements of the urethra were taken at 4 defined points: at urethrovesical junction (UVJ), 17 mm below UVJ (middle of the urethra) and one centimeter above and below this point (upper and lower third). For evaluation of the proximal urethra the distance between the inner edges and depth of visible opening (funnelling) was measured at rest and at maximal Valsalva. Thickness of the bladder was measured after emptying at three points (anterior, trigone and dome).


For all women, we examined the changes in position and mobility of the whole urethra during maximal Valsalva maneuver and changes induced by the surgery. The mobility was expressed as vector and direction of the movement from rest to the maximal Valsalva maneuver. For three mobility groups (women with low, intermediate and high urethral mobility before surgery) we compared the changes induced by the operation and the typical position and mobility of the tape after surgery. Data were summarized as means and medians, with standard deviation (SD) and quantile range for measures of variability. Depending on the character of the data, either matched pairs t-test or Wilcoxon test were used to evaluate the changes occurring between Valsalva maneuver or induced by the operation. For comparisons between three mobility groups, ANOVA F-test or Kruskal-Wallis test were used where appropriate. The level of significance was set to 0.05. All analyses were performed using statistical software R, version 1.7.1. Results Mobility of the urethra before surgery did not differ from values common in incontinent patients as published in previous studies. The position of the urethra at rest is not influenced by the surgery (it is in the same position as before - Fig. 1a). The operation significantly decreased the mobility of all parts of the urethra during Valsalva - Fig. 1b. Women with high mobility before surgery had high mobility afterwards. For the different mobility groups there is no differences in the direction of the preoperative movement during Valsalva maneuver (Fig. 2). The rest position of the tape with respect to the lower urethral segment is the same for all groups; hence preoperation mobility type did not influence the position of the tape (Fig. 2). The absolute changes of the vector of the urethral movement is different according the mobility group (average decrease is 6 mm, for women with low mobility 2-3 mm, intermediate 4-6, high 9 mm). The change of the relative mobility (in percentage) is the same in all groups. The operation did not influence the proximal urethra at rest and significantly decreased funnelling during maximal Valsalva (width and depth). After the surgery there was a slight increase in the thickness of the bladder wall (anterior and trigone), by 0.64 and 0.73 mm respectively. Fig. 1. Comparison of the position of the urethra before and after surgery 1a. At rest 1b. At maximal Valsalva

-40 -30 -20 -10 0 10

-10

010

2030

40

x

y

At restbeforemean urethraaftermean urethra

beforemean urethraaftermean urethra

-40 -30 -20 -10 0 10 20

-20

-10

010

2030

40

x

y

At maximal Valsalvabeforemean urethraaftermean urethra

beforemean urethraaftermean urethra

Fig. 2 Before surgery

-40 -30 -20 -10 0 10 20

-20

-10

010

2030

40

x

y

Low mobility

Before surgery

at restmean urethraat maximal Valsalvamean urethra


-40 -30 -20 -10 0 10 20

-20

-10

010

2030

40

x

y

Intermediate mobility

Before surgery



-40 -30 -20 -10 0 10 20

-20

-10

010

2030

40

x

y

High mobility

Before surgery




After surgery

-40 -30 -20 -10 0 10 20

-20

-10

010

2030

40

x

y

Low mobility

After surgery



-40 -30 -20 -10 0 10 20

-20

-10

010

2030

40x

y

Intermediate mobility

After surgery



-40 -30 -20 -10 0 10 20

-20

-10

010

2030

40

x

y

High mobility

After surgery



Interpretation of results Successful TVT procedure did not influence the position and proximal urethra at rest but significantly

decreased the mobility of the urethra during Valsalva. The tension of the tape should be different for different patients.

Concluding message The information about the type of the urethral mobility is important for the surgeon and may increase the success rate of TVT procedure. Funding - supported by the Grant Agency of the Ministry of Health of the Czech Republic grant No. NH 6982-3 69 Jain S1, Duckett J1

1. Medway Maritime Hospital GROIN PAIN FOLLOWING TENSION FREE VAGINAL TAPE (TVT) : MANAGEMENT STRATEGIES Aims of study To review different treatment strategies for the women with groin pain following tension free vaginal tape (TVT) procedure. Study design, materials and methods This series consisted of 450 women who underwent TVT procedure between November 1999 to October 2003. The follow-up ranged from 3 to 50 months. Five women reported significant groin pain that had not improved six months after surgery and were offered further treatment. The pain was not related to posture. One woman was reffered from another centre and received treatment. Women with pain were initially treated conservatively and in the majority the pain resolved and did not merit further treatment. The initial management of four women included local infiltration of depomedrone and bupivacaine. Eighty milligrams of depomedrone (2ml with 40mg per ml) and 10 ml of 0.5 % bupivacaine was injected into the most tender area( 1). In all four women this was located at the posterior superior aspect of the symphysis. The procedure was performed in the out-patient clinic under aseptic conditions. All subjects were reassessed 6 weeks and six months after treatment. There were no systemic side effects due to the injection. The remaining women developed recurrent pain after an initially successful injection. They underwent dissection and excision of the TVT with significant pain reduction. The procedure was performed under general anaesthesia in all 3 women. The patient was place in dorso–lithotomy position with vaginal/perineal preparation and draping. An oblique incision was performed over the area of maximal tenderness. The pubic tubercle and superficial inguinal ring were identified and an area between the skin and upper border of the symphysis was explored. In all women, the tape was found to be encased in adhesions medial to superficial inguinal ring.


The tapes were encased in adhesions forming a thick, cord like structure, with strands of the mesh visible in the surface. Approximately four centimeters of the tape was excised from the level of the top of the symphysis to the insertion into the skin (2). All the patients remained continent following surgery. Patients were asked to grade their pain on a score from zero to ten. Zero was no pain at all whilst ten was the most severe pain imaginable. Results Five women of 450 women presented with groin pain persisting at least 3 months after surgery (1.1%). One of the four women was cured of her pain and did not require further treatment. One woman failed to improve with an injection of local anaesthetic and steroid but did not request further more major intervention. Three women were initially cured of their pain but two relapsed and required tape excision with good effect. A third woman referred from another centre was primarily treated with tape excision. All remain dry by subjective reports after tape excision. There were no side effects from the steroid/local anaesthetic injection. In the three women who had tape excision, the pain scores reduced from 8.7 to 0.7. Interpretation of results Groin pain is a complication of TVT procedure with an approximate incidence of 1.1% in our experience. If conservative management fails to relieve symptoms, pain can be treated by injecting a mixture of steroid and local anaesthetic. More severe symptoms may require TVT mesh dissection and excision, which was performed in 3 women. Excision of the distal end of the tape provided significant pain relief in all women. Concluding message The incidence may be greater than this but this symptom may not be readily volunteered. Groin pain can be treated with combination steroid injection and local anaesthetic but the effect may not be long lasting. Persistent pain is best treated with excision of the distal end of the tape. References 1. Surgical management of groin pain of neural origin. J Am Coll Sur 2000; 191(2): 137-42. 2. Postural perineal pain associated with perforation of the lower genital tract due to insertion of a tension-free vaginal tape. BJOG 2003; 110: 79-82. 70 Piskunova E1, Golubkov N 11. Cosmetology and Plastic Surgery Centre EXPEDIENCY OF UROGENITAL PATHOLOGY CORRECTION COMBINED WITH ABDOMINOPLASTY IN A PLASTIC SURGERY CLINIC Hypothesis / aims of study To prove the expediency of simultaneous sling procedures for stress urinary incontinence (SUI) and/or surgical treatment of genital prolapse in women undergoing abdominoplasty. Study design, materials and methods According to our examination algorithm, all female patients seeking plastic surgery are routinely examined by a gynecologist for possible pathology and its timely treatment during simultaneous surgery. Between 2002 and 2003, 165 abdominoplasty procedures accompanied by aponeurosis suturing were performed in our clinic. Gynecological examination revealed genitourinary problems in 92 female patients undergoing abdominoplasty. The study group included 45 perimenopausal and postmenaupausal females (46 to 60 yo) with some degree of genital prolapse and SUI signs, who underwent gynaecological surgery combined with abdominoplasty. The controls consisted of 47 patients of similar age and genitourinary signs who underwent abdominoplasty but refused to have any gynecological surgery. The study group was subdivided into 4 subgroups: Subgroup 1 (n=2) aged 46 to 52, had the history of 2 births and gynecological operations. They had SUI confirmed by ultrasonic and urodynamic studies. No genital prolapse was found. Both patients underwent classical posterior-pubic urethropexy using tension-free vaginal tape (TVT).


Subroup 2 (n=17) aged 46 to 56, had the history of 1 to 3 births, 7 patients had the history of gynecological surgeries. All patients had SUI combined with genital prolapse. Surgical treatment for prolapse in combination with classical TVT was performed in this subgroup. Subgoup 3 (n=2) aged 46 to 56, had the history of 1 to 3 births, the history of gynecological surgeries, II or III degree obesity and SUI combined with genital prolapse. Surgical treatment for prolapse in combination with transobturator suburethral tape (T-O-T) for SUI was performed. Subgroup 4 (n=24) aged 46 to 56, had the history of 1 to 3 births, the history of gynecological surgeries and present genital prolapse. Surgical treatment for prolapse was performed. Results The results were assessed during follow-up visits by interviews and questionnaires. The follow-up period was 1,5 years. Study group. Twenty-two out of 45 (48,9%) patients evaluated their gynecological health as very good, 17 (37,8%) – good and 6 (13,3%) – satisfactory. Controls. Twenty-nine (62%) patients were readmitted to the Gynecology Department of our clinic to deal with their growing urogynecological problems. The patients observed aggravation of their condition some time after their abdominoplasty procedure, i.e.: 1-2 weeks postoperatively (8 patients, 27.5%), 3 to 4 months postoperatively (16 patients, 55.2%) and 8 to 10 months postoperatively (5 patients, 17.3%). The readmitted patients underwent the following surgeries: T-O-T (n=2), TVT (n=5), surgical treatment for genital prolapse (n=12), TVT combined with prolapse treatment (n=10). Interpretation of results The study showed higher degree of satisfaction in patients operated on for SUI and genital prolapse simultaneously with abdominoplasty than in controls who refused to undergo any gynecological surgery and experienced worsening of their condition within 1 week to 10 months postoperatively. The aggravation of genitourinary condition in female patients after abdominoplasty was associated with reduced volume of abdominal cavity, higher abdominal pressure and consequently higher pressure on the pelvic floor, which resulted in greater genital prolapse and onset or aggravation of existing SUI. Simultaneous gynecological surgery and abdominoplasty could increase the following complications: delayed micturition in early postoperative period (from average 13.7% to 18%); bladder perforation during classical TVT urethropexy when TVT was performed after abdominoplasty, which was associated with anatomical landmarks shift (from average 1.8% to 6%). Concluding message

1. Abdomioplasty requires simultaneous surgical correction of genital prolapse and/or SUI in female patients with this pathology.

2. Abdominoplasty is a risk factor for genital prolapse and SUI progression. 3. TVT (T-O-T) should be performed prior to abdominoplasty, with original pelvic landmarks and bladder topography. 4. T-O-T is an operation of choice for SUI combined with abdominoplasty, particularly in patients with obesity and

history of gynecological surgery. 71 Arya L1, Novi J1, Clemons J2, Myers D3

1. Hospital of University of Pennsylvania, 2. Madigan Army Medical Center, 3. Brown University VAGINAL PARAVAGINAL REPAIR USING PORCINE OR HUMAN CADAVERIC DERMAL GRAFT: A SURVIVAL ANALYSIS Hypothesis / aims of study To compare objective failure rate following vaginal paravaginal repair for anterior vaginal wall prolapse using either porcine or human cadaveric dermal graft. Study design, materials and methods A retrospective repeated measures cohort study approved by Institutional Review Board included all vaginal paravaginal repairs (n= 117) for anterior vaginal wall prolapse stage II or greater performed between January 2001 and August 2003. Between January 2001 and July 2002 all paravaginal repairs were performed with


cadaveric dermal graft and were compared to all repairs performed between August 2002 and August 2003 with porcine dermal implant. Anterior vaginal wall prolapse was staged preoperatively and every 6 months postoperatively. All terms, definitions, and descriptions confirm to standards recommended by the International Continence Society. Changes in functional status (urinary symptoms, prolapse symptoms, and sexual activity), and complications were recorded at each visit. Objective failure was defined as recurrent anterior vaginal wall prolapse, stage II or greater. Life-table analysis including log-rank test were used to determine risk for objective failure and compare survival curves. Risk factors for recurrent anterior vaginal wall prolapse were evaluated. Vaginal paravaginal repair of anterior vaginal wall prolapse involved vaginal dissection to identify the arcus tendineus fascia pelvis. Either porcine dermal or human cadaveric graft was attached to the arcus using permanent multifilament suture (00). Results There was no significant difference in the mean age (62.5 vs. 65.3 years), parity (2.3 vs. 2.5) weight (153.5 vs. 157.1lbs), race (85% Caucasian vs. 87%), hormone replacement (43% vs. 49%) and prior prolapse surgery (62% vs. 55%) of the porcine dermal and cadaveric dermal graft groups respectively. Preoperative clinical findings were not significantly different in the two groups. Table 1: Preoperative clinical findings in the two groups.

Porcine Implant (N=72) Cadaveric graft (N= 45) P value Vaginal bulge 68 (95%) 43 (97%) NS Stress urinary incontinence 26 (36%) 14 (31% NS Urge incontinence 27 (38%) 16 (36%) NS Voiding difficulty 10 (14%) 6 (13%) NS Stage II anterior wall prolapse 9 (13%) 8 (18%) NS Stage III anterior wall prolapse 46 (64%) 27 (60%) NS Stage IV anterior wall prolapse 17 (23%) 10 (22%) NS Vault prolapse 52 (73%) 30 (67%) NS Posterior wall prolapse 70 (98%) 43 (96%) NS Concurrent prolapse surgery 70 (98%) 43 (96%) NS

The median length of follow up for the cohort was 22 months (range 19-28 months) in the cadaveric dermal and 18 months (range 7-20 months) in the porcine dermal group. Postoperatively, 31 (69%) women in the cadaveric dermal group had objective failure as compared to 3 (4%) in the porcine dermal group (p = <.0001). Life-table analysis of the postoperative 6-month interval examinations demonstrated that the cumulative probability of an objective failure in the cadaveric dermal group was 0.2 (95%CI 0.1-0.3) at 6 months, 0.30 (95%CI 0.1-0.33) at one year, 0.45 at 1.5 years (95% CI 0.1-0.7), 0.5 (95% CI 0.2-0.7) at 2 years, 0.5 at 2.5 years (95% CI 0.2-0.8). In the porcine dermal group, the cumulative probability of an objective failure was 0.1 at 6 months, 0.12 (95% CI 0.05-0.25) at one year, 0.15 at 1.5 years (95% CI 0.09-0.33) and 0.15 at 20 months (95% CI 0.09-0.33) (Figure 1). The relative risk for objective failure for the porcine dermal group was 0.2 (95% CI 0.1, 0.5), p < 0.01) as compared to the cadaveric dermal group.

0

10

20

30

40

50

60

70

80

90

100

6 12 18 24 30

Months

Est

mat

ed P

ropo

rtion

s (%

)

CadavericPorcine

Figure 1. Survival Curves for cadaveric and porcine dermal groups


The rate of other post-operative complications in the porcine dermal and cadaveric dermal groups was not significantly different (recurrent urinary incontinence 12% vs. 21%, dyspareunia 4% vs. 2%). No graft erosions were noted in either group. No identifiable risk factors for objective failure were found among the demographics, grade of prolapse, co-existent prolapse, and prior pelvic surgery. A concurrent suburethral sling procedure did not prevent objective failure (Fisher’s test, P= 0.75). Interpretation of results The rate of recurrence of anterior vaginal wall prolapse following vaginal paravaginal repair with cadaveric graft (69%) was significantly greater than with porcine dermal graft (4.2%). Since the duration of follow up was greater for the cadaveric dermal group than the porcine dermal group, we used survival analysis to “censure” patients from further analysis on the date of recurrence. Survival analysis confirmed that the risk of recurrence of anterior vaginal wall prolapse was significantly lower with vaginal paravaginal repair using porcine dermis as compared to cadaveric dermis. Additionally, no other risk factor for objective failure was found in demographic variables, grade of prolapse, co-existent prolapse and concurrent procedures. Concluding message The risk of recurrence of anterior vaginal prolapse is lower following vaginal paravaginal repair using porcine dermal implant as compared to cadaveric dermal graft. 72 Suzuki K1, Ukimura O1, Ushijima S1, Hirahara N1, Itoh T2, Hagiwara A2, Nakamura T3, Shimizu Y3, Miki T1 1. Dept of Urology, Kyouto Prefectural Univ of Medicin, 2. Dept of Digestive Surgery, Kyoto Pref Univ of Medicine, 3. Dept of Bioartificial organs, Inst for Frontier Medical Sciences, Kyoto Univ REGENERATION OF HYPOGASTRIC NERVE USING A POLYGLYCOLIC ACID(PGA)-COLLAGEN NERVE CONDUIT FILLED WITH COLLAGEN SPONGE PROVED ELECTROPHYSIOLOGICALLY IN A CANINE MODEL Hypothesis / aims of study A new type of a biodegradable artificial nerve conduit, polyglycolic acid (PGA)-collagen nerve conduit filled with collagen sponge, has been developed and evaluated for peripheral nerve regeneration (1,2). The hypogastric nerve (HGN) is a sympathetic nerve and controls urinary and seminal functions. Bilateral HGN are often excised in the operations of malignant tumors, such as prostate cancer, bladder cancer, and rectal cancer, because of the local extension of the tumor or lymph node dissection. Although autonomic nerve preserving procedures have been attempted to avoid functional disturbance during such operations, the efficacy and indication are still limited. Autonomic nerve regeneration using an artificial nerve conduit has not yet been reported. The aim of this study is to determine whether the gap of HGN was interposed with the aid of this new artificial nerve conduit, PGA-collagen nerve conduit filled with collagen sponge in a canine model, and the period of functional recovery was determined electrophisiologically 4-8 months intervals after the operation. Study design, materials and methods Twelve adult male beagle dogs were divided into 2 groups, the control group (n=2) and the implanted group (n=10). The right HGN was cut with surgical scissors and a 10 mm long segment of HGN was removed. A PGA-collagen nerve conduit (tube with 2mm in diameter) with a length of 20 mm was interposed in the 10 mm gap. Each end of the tube was cut longitudinally 5 mm along the length of the conduit, and the proximal and distal nerve stumps end of the HGN were inserted into the opened part of the nerve conduit to a depth of 5mm (gap=10mm). The end of the stumps of the HGN was fixed to the conduit at the edge of the cut and the longitudinal cut lines were closed without suturing the nerve. The regeneration of the HGN was evaluated electrophysiologically 4 months (n=2), 5 months (n=2), 6 months (n=2), 7 months (n=2) and 8 months (n=2) after the operation, by stimulating the lumbar splanchnic nerves (LSNs) from L2 to L4 and measuring the response of the spermatic duct, bladder neck, and prostate. Before the nerve stimulation in all of the dogs, the left HGN was transected to eliminate the substitutive pathways.


Results In the control, electrostimulation of the left LSNs induced elevation of intraluminal pressure of the spermatic duct (80 mmHg amplitude, and 10 seconds duration), elevation of bladder neck pressure (20mmHg amplitude), and prostate contraction (25 seconds duration). When the right HGN was transected after the measurement, no response was observed by the stimulation of the left LSNs (contro). In the dogs with 7 months as well as 8 months follow-up, electrostimulation of left LSNs elicited elevation of intraluminal pressure of the spermatic duct (about 80mmHg, and 10 seconds), elevation of bladder neck pressure (about 25 mmHg, and 20 seconds), and prostate contraction (20 seconds). After the excision of the area of the interposed right HGN, no response was observed. In the dogs with 4, 5, or 6 months follow-up, no response was observed by stimulation of the left LSNs. Interpretation of results These results proved that the regeneration of HGN using new PGA-collagen nerve conduit could be achieved within 8 months. Concluding message The HGN could be regenerated across a 10mm gap with 7 or 8 months follow-up with the aid of a PGA-collagen nerve conduit filled with collagen sponge. The regeneration of HGN using this nerve conduit will be great help for patients who suffer from urinary and seminal disturbance. 73 Yoshida M1, Inadome A1, Masunaga K1, Sugiyama Y1, Otani M1, Iwashita H1, Miyamae K1, Ueda S1 1. Department of Urology, Kumamoto University School of Medicine NON-NEURONAL ACETYLCHOLINE AND ATP RELEASES FROM ISOLATED NORMAL AND NEUROGENIC HUMAN BLADDER Hypothesis / aims of study The main neurotransmitter in bladder contraction is acetylcholine released from cholinergic nerve endings. However, non-adrenergic and non-cholinergic neurotransmitters may contribute to contractions in human bladder with pathological conditions or aged bladder. It has been reported that adenosine triphosphate (ATP) is the most important NANC neurotransmitter in bladder contraction. Furthermore, several reports suggest the releases of ACh and ATP from the non-neuronal origin, especially from urothelium (1, 2). Bladder stretch may cause the increases in non-neuronal ACh and ATP releases, which may be the stimulating factors for afferent nerves resulting to increase in micturition reflex. The present study was designed to evaluate the differences in non-neuronal ACh and ATP releases from isolated normal and neurogenic human bladder. Study design, materials and methods Human bladders were obtained from 10 patients (control group), who were undergoing cystectomy due to bladder carcinoma, and 8 patients (neurogenic bladder group: 3 cases: spina bifida; 5 cases: spinal cord injury) who had undergoing bladder augmentation. Bladder strips with or without urothelium were suspended in organ bath filled with Krebs-Henseleit solution, and tension developments were recorded in both groups. Microdialysis probe was inserted into the strip, and Ringer solution was perfused into the probe at a constant flow rate. The effects of elevation of the resting tension (0 to 4 g) induced by strip stretching on non-neuronal ACh and ATP releases were also evaluated. The amount of ACh and ATP in the dialysate fraction by HPLC with ECD, and luciferine-luciferase assay, respectively. Results In the control and neurogenic human bladders strips, there were non-neuronal ACh and ATP releases, which were not inhibited by treatment with tetrodotoxin. The non-neuronal ACh (table 1) and ATP (table 2) releases from strips with urothelium were significantly higher than that from strips without urothelium in both groups. In the neurogenic group, basal ACh and ATP release with urothelium was about 4.6 and 14.7 times higher than that without urothelium, respectively. Stretch of the strips without urothelium did not cause any significant increases in non-neuronal ACh and ATP releases in both groups. However, in strips with urothelium, stretch of


bladder strips caused significant increase in ACh and ATP releases. In the neurogenic group, ACh and ATP releases in the stretch condition were about 5.6 and 11.2 times higher than that in the basal condition, respectively. Interpretation of results The present data showed that there are ACh and ATP releases from non-neuronal origin in the control and neurogenic human bladder. Urothelium may partly contribute to non-neuronal ACh and ATP releases, and bladder stretch caused increase in both non-neuronal ACh and ATP releases. In the neurogenic bladder, the basal and stretch-induced release in non-neuronal ATP release was more prominent, as compared with ACh release. Concluding message The present study suggests that the non-neuronal ACh and ATP are partially released from urothelium in the control and neurogenic human bladders. Both non-neuronal ACh and ATP may have an important role on the regulation of bladder function. ATP may have a relative contribution to detrusor dysfunction in the neurogenic bladder. References 1) Urology 63 (Suppl 3A) 17-23, 2004. 2) J. Neurosci. 21: 5670-5677, 2001. Table 1 Non-neuronal ACh releases (fmol/g tissue) from control and neurogenic human bladder

Group Urothelium Basal release (Resting tension 0 g)

Release in stretch (Resting tension 4 g)

With 43.5 ± 5.9# 198.7 ± 20.3*# Control (n=10) Without 15.6 ± 3.8 23.2 ± 6.8

With 105.8 ± 12.5# 588.7 ± 66.5*# Neurogenic (n=8) Without 23.2 ± 5.2 33.7 ± 6.0

* Significantly different from the comparable value for resting tension 0 g (P<0.05) # Significantly different from the comparable value without urothelium (P<0.05) Table 2 Non-neuronal ATP releases (fmol/g tissue) from control and neurogenic human bladder

Group Urothelium Basal release (Resting tension 0 g)

Release in stretch (Resting tension 4 g)

With 18.7 ± 3.2# 32.4 ± 5.3*# Control (n=10) Without 4.5 ± 0.5 6.8 ± 1.1

With 85.5 ± 11.5# 957.9 ± 115.4*# Neurogenic (n=8) Without 5.8 ± 1.8 9.5 ± 2.0

* Significantly different from the comparable value for resting tension 0 g (P<0.05) # Significantly different from the comparable value without urothelium (P<0.05) 74 Hosoi T1, Yokota T1, Turuya Y1, Matuoka T1, Yamaguchi O1

1. Department of Urology, Fukushima Medical University ESTROGEN SIGNIFICANTLY INFLUENCES DETRUSOR CONTRACTILITY IN FEMALE RATS Hypothesis / aims of study Lower urinary tract dysfunctions that occur after menopause, such as detrusor overactivity, stress urinary incontinence and detrusor underactivity, are thought to be due in part to estrogen deficiency. It is therefore hypothesized that estrogen replacement therapy may be useful for stress incontinence and detrusor overactivity. However, little attention has focused on detrusor underactivity and the possibility that estrogen deficiency may concern this condition. If detrusor contractility is impaired in elderly female, the management of bladder dysfunction would be more complicated. The role of estrogen in bladder function has been studied using the ovariectomized animal models. Although many studies have shown that ovariectomy alters the contractile responses of detrusor muscle to carbachol, ATP, KCl and electric nerve stimulation, no studies have evaluated the effects of estrogen on contractility itself (the contraction strength) which is defined as the mechanical power generated by detrusor contraction.


Thus, in the present study, we evaluate whether the contraction strength of detrusor decreases after estrogen depletion by ovariectomy and reverses from this decrease upon estrogen replacement. Study design, materials and methods A total of 30 female Sprague-Dawley rats (16 weeks old) were divided into three groups including sham operated (SHAM), bilateral ovariectomy (OVX) and bilateral ovariectomy plus estrogen replacement (OVX+E). The OVX+E group was treated with estradiol at 3mg/kg/week subcutaneously. At 4 weeks after surgery, detrusor strips were taken from the bladder and suspended in a organ bath. Transmural electrical stimulation (15V, 0.5msec duration, 50Hz) was applied to detrusor strips in order to induce contraction. The shortening responses to electrical stimulation under various loads (4.9 mN to 19.6 mN) were recorded using an isotonic transducer. At each contraction, the applied load was regarded as force generated (F), and velocity of shortening (V) was calculated from the shortening curve of a muscle strip. The relation between F and V was analyzed using a computer (Microsoft Excel Solver) to investigate whether F / V plots were governed by the Hill equation. The strength of contraction was defined as the total mechanical power (P) produced in each detrusor strip, which is given by the following Hill equation; P = FV + aV + bF = bFiso, where a and b are parameters characteristic of the muscle, and Fiso was an isometric force (i.e., under this load the strips were never shorten). After the contraction study, wet weight of each strip was measured. Results The force (F) / velocity (V) plots obtained from the isotonic contraction study were well fitted to the Hill equation (Fig.1). Thus, contraction power (P), isometric force (Fiso), a and b for each strip could be determined. As shown in Fig.2, the contraction power (per unit tissue weight) of OVX group (mean ± SD) was 3.24 ± 0.19 mwatt/g and significantly lower than that of SHAM group (5.37 ± 0.28 mwatt/g). However, the contraction power of OVX + E group was approximately the same as that of SHAM group (Fig.2). Concluding message The results of this study showed that ovariectomy decreased the contraction power in rat detrusor muscle, and the estrogen replacement improved it. This may suggest that estrogen plays a role in maintaining detrusor muscle power. The mechanism by which estrogen influences detrusor contractility remains unclear. As recent studies suggest, it may be speculated that estrogen modulates the expression of contractile proteins or protects the bladder against collagen formation. A clinical implication from our study is that estrogen replacement may be beneficial for treating postmenopausal detrusor underactivity.

Force - Velocity curve

0123456

0 10 20 30 40 50

Force (mN)

Velo

city

(mm

/sec

)

�£OVX+E�›SHAM�¡OVX

�£

�£�£

�£�£

�£

�£�›

�›

�›

�›�›

�›

�›�¡�¡

�¡�¡

�¡�¡

�¡


0123456

0 10 20 30 40 50

Force (mN)

Velo

city

(mm

/sec

)



0123456

0 10 20 30 40 50

Force (mN)

Velo

city

(mm

/sec

)


�£

�£�£

�£�£

�£

�£�›

�›

�›

�›�›

�›

�›�¡�¡

�¡�¡

�¡�¡

�¡

Power per unit tissue weight

0

1

2

3

4

5

6

7

SHAM OVX OVX+E

P(wa

tt) (

10-3

)

* ** : p < 0.001


0

1

2

3

4

5

6

7

SHAM OVX OVX+E

P(wa

tt) (

10-3

)


0

1

2

3

4

5

6

7

SHAM OVX OVX+E

P(wa

tt) (

10-3

)

* ** : p < 0.001

(Fig.1) The force / velocity curve was determined from

one detrusor strip. (Fig.2)


75 Du S1, Araki I1, Mikami Y1, Kamiyama M1, Beppu M1, Takeda M1

1. Department of Urology, University of Yamanashi Faculty of Medicine DIFFERENTIAL EXPRESSION OF EPITHELIAL SODIUM CHANNELS IN THE HUMAN AND RAT URINARY BLADDER EPITHELIUM WITH AND WITHOUT OUTLET OBSTRUCTION Hypothesis / aims of study The overactive bladder (OAB) symptoms usually result from detrusor overactivity. Detrusor overactivity (DO) occurs in association with bladder outlet obstruction (BOO). The increase of afferent activity is one of the possible mechanisms for this idiopathic DO. The epithelial sodium channels (ENaC) expressed in the mammalian urothelium seem to be mechanosensitive. In the rabbit bladder, ENaC has the ability to change their sodium transport properties following changes in hydrostatic pressure. The ENaC in the pelvic epithelium of rats has been shown to participate in the activation of afferent renal mechanosensitive neurons by increased renal pelvic pressure. Thus, ENaC in the bladder epithelium might be involved in mechanosensory transduction mechanism. We examined whether the ENaC is expressed in the human and rat urinary bladder and how its expression changes in association with BOO. Study design, materials and methods Samples of the human bladder mucosa were obtained from 9 controls and 9 patients with BOO. The criteria for BOO included the International Prostate Symptom Score (IPSS) of more than 12 points, the prostate volume of more than 30 ml, and urodynamic tests (Qmax of less than 10 ml/sec and pressure flow study). In 7 patients with BOO, involuntary detrusor contraction was demonstrated. Female Sprague-Dawley rats (10 weeks old, 200-220 g) were deeply anesthetized with sodium pentobarbital and the whole bladder was removed. Under stereoscopic microscope, the bladder mucosa was dissected from others in 5 controls and 5 rats with BOO and stored at -80 °C. To establish partial urethral obstruction, a ligature of 4-0 silk was tied around the proximal urethra with an indwelling one mm diameter polyethylene tubing under sodium pentobarbital anesthesia and then the tubing was removed three weeks before the experiment. The expression and localization of ENaC proteins was examined using immunofluorescent staining. Rabbit anti-ENaC α, β, γ subunit polyclonal antibodies were used as a primary antibody. Antibody reactions were detected with TRITC-conjugated swine anti-rabbit immunogloblin and viewed with a fluorescence microscpore. The quantification of ENaC genes expression was assessed by a real-time RT-PCR with a Smart Cycler System using SYBR green I as the fluorogenic dye. The gene-specific primers for ENaC α, β, γ subunit designed with the online program Primer 3. The ENaC expression was normalized as the ratio (%) to GAPDH expression in each sample. Amplified PCR products were electrophoresed on 2 % agarose gel and visualized with ethidium bromide. Some PCR products were purified and sequenced using an automated sequencing machine to identified the target gene. Results Immunofluorescent Staining In the human, the α-, β-, γ-hENaC proteins were found to be expressed in the bladder epithelium with BOO, whereas the α- and γ-hENaC proteins were virtually unstained in control bladders. In the rat, the α-, β-, γ-rENaC proteins were clearly expressed in the both bladder epithelia with and without BOO. Quantitative Real-Time RT-PCR In the human, the α-, β-, γ-hENaC mRNAs were detected in 1, 6 and 4 of 9 control bladder mucosa, respectively. Thus, the expression of α subunit was disproportionately low in controls. On the other hand, each hENaC mRNA was clearly present in all bladders with BOO. The expression levels of each subunit in the bladder with BOO were significantly higher than those in controls (p = 0.0002 for α-subunit; p = 0.007 for β subunit; p = 0.0005 for γ subunit). In the rat, the α-, β-, γ-rENaC mRNAs were present in all bladder mucosa with and without BOO. The expression levels of each subunit were not quantitatively different between bladders with and without BOO. Interpretation of results The ENaC expression in the bladder epithelium showed a remarkable species difference between the human and rat. The ENaC expression was very poor in the normal human bladder, whereas it is clearly demonstrated in the normal rat bladder. In the human, our result indicated that BOO induces the over-expression of ENaC in


the bladder epithelium. Most of patients with BOO sampled for this study showed DO. Thus, the ENac expression might be involved in the induction of DO due to BOO (idiopathic DO) in the human. Concluding message There is a remarkable species difference in the expression of ENaC in the bladder epithelium. In the rat, the mechanosensitive ENaC expressed in the bladder epithelium may be a good candidate for the mechanosensory transduction mechanism in the urinary bladder. In the human, the increased ENaC expression might be involved in the induction of DO due to BOO. 76 Sato K1, Takimoto Y1, Igarasi T1, Sugimoto S1, Kodama M2, Wada Y2, Kokubun S1, Yosida T1

1. Department of Urology, Nihon University School of Medicine, 2. Department of Physiology, Nihon University School of Medicine LONG TERM INVESTIGATION OF MICTURITIONAL PATTERNS AND TISSUE CONTENT OF NERVE GROWTH FACTOR IN THE URINARY BLADDER OF STREPTOZOTOCIN-INDUCED DIABETIC RATS Hypothesis / aims of study Nerve growth factor (NGF) is a biomolecule, which is produced within the innervated target organs. NGFs move to neural cells by axonal transport and participate in differentiation, induction and maintenance of neurons. Previously we reported about tissue content of NGF in the urinary bladder ([bladder NGF]) in streptozocin (STZ) induced diabetic rats. In the early phase from induction, [bladder NGF] rose above the physiological range. In this study, we present results in long-term investigation for micturitional patterns and [bladder NGF] in STZ induced diabetic rats. Study design, materials and methods (1) Materials 27 subjects of 7 to 11 week old female Wister rats were used. We divided them into three

groups. In STZ group, rats were made diabetic by a single injection of STZ diluted with 0.1 M citrate buffer (60mg/kg, i.p.) after fasting for 24 hours. All diabetic animals had blood glucose values > 250 mg/dl. For the references of evaluation, a diuretic control group fed with 5% sucrose (SUC) (SUC group) and normal control animals (Control group) were also maintained.

(2) Evaluated parameters The time course of micturitional pattern and [bladder NGF] were recorded and measured on the day 7, 14, 28, 56, 84 after the induction.

(2) Statistical analysis Obtained parameters were evaluated by the Mann-Whitney U test for the difference between the STZ, SUC and Control group at significance levels of p<0.05.

Results 1. The tidal voided volume in STZ and SUC groups increased from induction. Both groups maintained the

increased volume at 3 months after the onset. 2. On day 7, [bladder NGF] significantly increased both in the SUC and STZ groups, showing 4 folds and 2

folds higher values than Control group. However, on day 84, [bladder NGF] in STZ group declined to the half of the value in Control group, where as [bladder NGF] in SUC group maintained above the value in Control group (Table 1).

Concluding message In the early phase of this experiment, STZ group showed more increase in [bladder NGF] than SUC group at the level above the physiological range. We assessed this difference is caused by hyperglycemia in addition to the adaptive increase of [bladder NGF] for the polyuric state. In the late phase, we revealed [bladder NGF] in STZ group declines to the half of the values of Control and SUC group. This suggests decrease of [bladder NGF] should be a cause of neurogenic bladder in established diabetes mellitus. Table 1 0 day 7 day 14 day 28 day 56 day 84 day STZ group 5.05±0.15 29.53±1.81 10.00±0.51 6.16±1.95 2.32±0.66 2.01±1.05 SUC group 4.99±0.22 13.86±0.92 6.06±0.66 5.11±0.49 4.83±1.11 4.95±0.65 CON group 5.01±0.21 4.91±0.19 4.82±0.17 4.99±0.13 5.11±0.16 5.09±0.23


77 Nakamura Y1, Tsujimoto G 2, Tanoue A 3, Ikegaki I 4, Shinozaki S 1, Nimura T 1, Matsuda Y 1, Kawatani M 1 1. Akita University School of Medicine, 2. Kyoto University, 3. National Research Institute for Child Health and Development, 4. Institute for Life Science Research, Asahi Kasei Corporation IS ALPHA-1D ADRENERGIC RECEPTOR RESPONSIBLE FOR STORAGE SYMPTOMS IN MICE? : EFFECTS OF ACETIC ACID ON BLADDER FUNCTION IN MICE LACKING ALPHA-1D ADRENERGIC RECEPTOR. Hypothesis / aims of study Alpha-1 adrenergic receptor (alpha-1 AR) antagonists are effective for relieving voiding and storage symptoms in patients with bladder outlet obstruction. Many investigators have reported that a highly selective alpha-1A AR antagonist did not appear to relieve storage symptoms in patients with benign prostatic hyperplasia (BPH) despite of a significant increase in urinary flow rate. Futhermore recent study reported that alpha-1 AR antagonist, which shows high affinity for both alpha-1A AR and alpha-1D AR, improved storage symptoms as well as voiding symptoms derived from BPH (1). The predominant subtype mRNA in bladder have been reported to be alpha-1D AR (2). We speculated that alpha-1D AR might be responsible for storage symptoms. Therefore, we evaluated the bladder function in mice lacking alpha-1D AR. Study design, materials and methods 1. Cystometry in conscious restrained mice. Male mice lacking alpha-1D AR (1D KO; n=7) and matching wild type control (WT; n=7), 11-12 weeks of age, were anesthetized with sevoflurane for surgical insertion of an intravesical catheter (PE-50). After the surgery, cystometry was performed in conscious restrained mice by infusing saline into the bladder at a constant rate (0.5 ml/hr). After control measurement, 0.1% acetic acid (AA) was infused intravesically. 2. Cystometry in conscious freely moving mice. For the purpose of excluding the influence on surgical procedure and restrained stress, further experiments were performed. Female 1D KO (n=31) and WT mice (n=31), 8 weeks of age, were anesthetized for surgical insertion of an intravesical catheter. Six days after operation, cystometry was performed in conscious freely moving mice by infusing saline or 0.1% AA into the bladder at a constant rate (1.2 ml/hr). 3. Measurements of noradrenaline release. Male 1D KO (n=4) and WT mice (n=4), 12-13 weeks of age, were studied in a room at 23-25 degrees centigrade with a 12/12-hour light-dark cycle. Individual mice were placed in mice metabolic cages. The urine was collected during 48 hours. The amount of noradrenaline released in the urine was measured by HPLC. Results 1. Cystometry in conscious restrained mice. Under control condition, there was no significant difference in any cystometric parameters between WT and 1D KO mice. In WT mice, intravesical infusion of 0.1% AA significantly decreased intercontraction interval (ICI) and pressure threshold (PT) (before AA, 657 ± 155 s, 6.6 ± 1.5 cmH2O; after AA, 281 ± 68 s, 4.4 ± 0.7 cmH2O, p<0.05, respectively). In 1D KO mice, neither ICI nor PT differ before and after intravesical infusion of 0.1% AA (before AA, 727 ± 89 s, 6.6 ± 0.9 cmH2O; after AA, 715 ± 93 s, 6.9 ± 1.0 cmH2O, respectively). There was no significant difference in maximal voiding pressure before and after intravesical infusion of 0.1% AA. 2. Cystometry in conscious freely moving mice. During intravesical infusion of saline, there was no significant difference in ICI between WT and 1D KO mice. During intravesical infusion of 0.1% AA, ICI in WT mice (150 ± 14 s) was significantly smaller than that in 1D KO mice (211 ± 27 s, p<0.05). 3. Measurements of noradrenaline release. The amount of noradrenaline released in urine of 1D KO mice (294.7 ± 93.3 pg) was significantly smaller than that in urine of WT mice (612.0 ± 53.5 pg, p<0.05). Interpretation of results 0.1% AA could not induce overactivity on bladder in 1D KO mice. Concluding message These findings indicated that alpha-1D AR might be responsible for storage symptoms in mice.


Figure: Cystometrogram in conscious restrained mice lacking alpha-1D adrenergic receptor KO0807.adicht

Cha

nnel

1 (c

mH

2O)

0

10

20

30

3:53:20 4:10:00 4:26:40 4:43:20 5:00:00 5:16:40 5:33:20 5:50:00891011 1213

2003/08/07 12:17:39.390

Event: 11 = ending point of intravesical infusion of saline; 13 = starting point of intravesical infusion of 0.1% acetic acid. References (1) The clinical efficacy of naftopidil on overactive bladder in patients with benign prostatic hyperplasia. Neurourol. Urodyn. 22: 437-438, 2003. (2) Alpha-1 adrenergic receptor subtypes in human detrusor. J. Urol. 160: 937-943, 1998. FUNDING: Grant-in-Aid for Scientific Research (C) (2) (15591675) from The Ministry of Education, Culture, Sports, Science and Technology of Japan 78 Ozkurkcugil C1, Komur O 1, Gokalp A1

1. Kocaeli University School of Medicine Urology Dept THE EFFECT OF MEMANTINE ON DETRUSOR OVERACTIVITY IN RATS WITH SPINAL CORD INJURY Hypothesis / aims of study Spinal cord injury results not only from the initial direct injury, but also from secondary damage via excitatory amino acid cascade (i.e. glutamate). High levels of exctracellular glutamate bind to N-methyl-D-aspartate (NMDA) and AMPA-Kainate receptors causing an increase in intracellular calcium that activates proteases, endonucleases and generates free radicals, all leading to neuronal cell death (1). Memantine acts as an open channel blocker, that enters the channel pore and sterically occludes the ion pathway (2). We evaluated the effect of memantine (glutamate receptor antagonist) on overactive detrusor after spinal cord injury in rats. Study design, materials and methods Ethical approval for the study was granted by the University Ethics Committee. Included in this study were 26 adult female wistar rats. Twelve animals served as normal controls, while 14 underwent spinal cord transection (clip compression technique) at the 10th thoracic vertebra. Fifteen days after spinal cord injury (SCI) 14 rats underwent filling cystometrogram (CMG) to confirm overactive detrusor, while another 12 served as normal control. Filling cystometrogram was performed in SCI animals before and after memantine treatment (16mg/kg, intraperitonealy). Parameters measured included voiding volume (VV), micturition pressure (MP), resting bladder pressure (RBP), a period between micturation (PM), and maximum pressure of overactive detrusor during filling period (OADPmx). The Mann-Whitney U test or Wilcoxon signed-rank test was used when appropriate for statistical data analysis. For all statistical tests, P<0.05 was considered significant.


Results The mortality rate was 66 % in SCI rats. Normal rats showed stable CMG; RP was 6.66± 3.02cmH2O, MP of 24.91±10.82cmH2O, PM of 38.33±8.30sc, and VV of 100-300µl. Compared with normal rats, SCI rats had high MP (44.37±21.89 versus 24.91±10.82cmH2O, P<0.05) and RP (14.75± 8.24 versus 6.66±3.02cmH2O, P<0.05). PM was slightly higher (48.25±41.32 versus 38.33±8.30sc, P>0.05) in SCI rats than normal animals. Overactive detrusor was found in 57.1% of the rats following SCI after fifteen days. Overactive detrusor resolved in 62.5 % of the animals that received 16mg/kg. memantine, intraperitonealy. All parameters for SCI rats were summarised in table 1. Table1. Parameters before memantine and after therapy in SCI rats. Parameters Before memantine

(mean±SD) (Range) After memantine (Mean±SD) (Range)

P value

MP(cmH2O) 44.37 ± 21.89 (20-91) 30.87 ± 14.74 (19-63) <0.05 PM(sc) 48.25 ± 41.32 (15-140) 65.37 ± 31.25 (30-120) >0.05 RP(cmH2O) 14.75 ± 8.24 (6-29) 10.12 ± 7.37 (5-22) <0.05 OADPmx cmH2O

* (20-92) * (0-38) *

*No SD was given related to a smaller extent for results of OADPmx Interpretation of results Overactive detrusor was found in 57.1% of the rats following SCI after fifteen days. More time may be necessary to see a greater amount of overactive detrusor following SCI in rats. On the other hand, the high mortality rate has restricted the time for the developing of overactive detrusor in SCI rats. Memantine as an open channel blocker eliminated overactive detrusor in 62.5 % of the rats after SCI. It is likely that this effect was due to the reduction of intracellular calcium by memantine (glutamate receptor antagonist). Concluding message Memantine may be an attractive way of treating overactive bladder. If this theory is supported by further clinical studies, memantine may be an alternative therapy besides antimuscarinic treatments for detrusor overactivity. References

1. Open-channel block of N-methyl-D-aspartate (NMDA) responses bye memantine: therapeutic advantage against NMDA receptor-mediated neurotoxicity. J Neurosci 12:4427-4436, 1992.

2. Neurogenic bladder for spinal cord injury:spinal cord microdialysis and chronic urodynamics. Brain Research Protocols 9:57-64, 2002

FUNDING: The Scientific Research Fund of Kocaeli University 79 Dambros M1, van Koeveringe G1, de Jongh R1, Bast A1, van Kerrebroeck P1

1. University Hospital Maastricht A LOW CONCENTRATION OF THE FLAVONOID AVOIDS THE PROGRESSIVE DECREASE OF BLADDER SMOOTH MUSCLE CONTRACTILITY INDUCED BY REPETITIVE FIELD STIMULATION. Hypothesis / aims of study There is increasing evidence that the generation of free radicals plays a role in the development of bladder dysfunction [1]. Studies have demonstrated that repetitive field stimulation (RFS) of smooth muscle strips isolated from the urinary bladder can be used to exhaust synaptic stores of acetylcholine and to produce direct neuronal damage [2]. Furthermore, RFS results in a significant increase in the accumulation of products of peroxidation within the smooth muscle membrane components which could be another cause of bladder


dysfunction [2]. Flavonoids are a group of polyphenolic compounds and have recently gained tremendous interests, due to their broad pharmacological activity. The pharmacological effect can be explained by their inhibition of certain enzymes and their antioxidant activity. To the best of our knowledge, this is the first time, the protective effects of the flavonoid Galangin, during RFS, on the progressive decrease of bladder smooth muscle contratile responses, are demonstrated. Study design, materials and methods Male pig detrusor strips were mounted between stainless steel hooks in 20ml organ baths containing Krebs-buffer solution which was aerated continuously with 5% CO2 – 95% O2, at 370C. Mechanical responses were recorded using an isometric force transducer. Measurements were started after an equilibration period of 60 min with an initial tension of 2g. After an initial equilibration time, all strips were stimulated at 32Hz, and subjected to a metacholine concentration curve (MCC), then the incubation medium was changed to one with the following additions for each of 6 experimental groups: all tissues in group 1 were incubated with normal krebs; those in group 2 with Galangin (0,1µM); group 3 with Galangin (0,1µM) + Propranolol (1µM); group 4 with Galangin (0,1µM) + Verapamil (0,1µM); group 5 with Galangin (0,1µM) + Phentolamine (1µM) and those in group 6 with Galangin (0,1µM) + Atropine (1µM). All strips were equilibrated in these buffers for 30 minutes then stimulated with Electrical field stimulation (EFS) at 32Hz and a MCC was performed. Six strips from each group were stimulated for 1,5 hours at 32Hz for 15 seconds every 5 minutes. At the end of the period of RFS, all strips were stimulated at 32Hz and a MCC was perfomed. After that, all strips were washed 4 times with fresh buffer (containing the group-specific additions described above) and all groups were subjected to 1,5 hours of incubation (recovery period); responses to field stimulation at 32Hz and the MCC were re-assessed. Student’s t-test and one factor ANOVA were used to determine the statistical significance to 0.05 levels. Results One and half hours of repetitive stimulation caused a progressive decrease in maximal contractile response to EFS and to a MCC (34% and 46% decrease, respectively – p < 0,05 versus initial response). Galangin avoided the progressive decrease in contractile response (the decrease of maximal contractile response was less than 3% - p > 0,05 versus initial response). Blockade of cholinergic and adrenergic nerves with atropine, phentolamine and propranolol did not modify the protective effect of galangin (p > 0,05). However, verapamil significantly reduced the effect of Galangin (the maximal contractile response decreased 36% - p < 0,05 versus group 2). Following the 1,5 hour period of recovery, the contractile responses to EFS and MCC in all groups showed no increase (p > 0.05 versus contractile responses after RFS). Interpretation of results We have demonstred that direct incubation of bladder smooth muscle in the presence of a low concentration of Galangin excerted a protective effect on bladder smooth muscle contractility by an action on L-type calcium channels and by reducing reactive oxygen species which are generated by repetitive field stimulation. Concluding message In the current experiments, Galangin excerted a protective effect from repetitive stimulation-induced fatigue. If the data are confirmed in-vivo, exogenenously administered Galangin might have a possible role in treating bladder dysfunction. References 1. Protective effect of vitamin E on the response of the rabbit bladder to partial outlet obstruction. J Urol 166: 341-346, 2001. 2. Effect of repetitive stimulation on the contractile response of rabbit urinary bladder subjected to in vitro hypoxia or in vitro ischemia followed by reoxygenation. Pharmacology 57: 139 - 147, 1998. 80 Ishihama H1, Kawatani M1, Ikeda M1, Momota Y1

1. Akita University School of Medicine ALPHA-1 ANTAGONISTS INHIBIT THE PRIMARY AFFERENT ACTIVITY FROM THE IRRITATIVE BLADDER OF THE RAT.


Hypothesis / aims of study Many reports show alpha-1 effects in the efferent systems to the urinary bladder. Alpha-1 facilitation for micturition reflex has been reported in the preganglionic neurons of spinal cord, in the pelvic ganglia and in the detrusor smooth muscle. Recently, a theory is coming out that alpha-1 antagonists inhibit the afferent limb in the lumbosacral cord (1). Then, we interested whether or not alpha-1 antagonist effects in the afferent systems. Many clinical data indicate alpha-1 antagonists tend to improve the irritative symptoms as well as obstructive symptoms. These data also suggest alpha-1 antagonist might act on the primary afferent systems, not only on the spinal cord. Since alpha-1 receptors were not identified at the primary afferent neurons, alpha-1 agonist and/or antagonist might act on the uroepitherium and nearby structures. Anyway, we examined the effects of alpha-1 antagonist on single unit-recording from the bladder afferent fibers in vivo. Study design, materials and methods We used Wistar female rats for these experiments (n=28). Rats were anesthetized by 0.9-1.0 mg/kg (i.p.) urethane. Double lumen catheter was inserted into the urinary bladder from external urethral orifice for infusion and recording the vesical pressure. Then, L3-L6 vertebrae were exposed and we selected very fine filament of the L6 dorsal root for recording the afferent activity from the pelvic viscera. We used alpha-1 antagonists, naftopidil (0.75-1.66 mg/kg) and tamsulosin (0.0001-0.01 mg/kg) for these experiments. Drugs were administered intravenously into the external jugular vein. Unit-recording was digitalized with AD converter and recorded in Power Lab System (version 5.0). The numbers of spikes/sec were counted with window discriminator. Results Naftopidil (1 mg/kg, i.v.) inhibited the rhythmic bladder contraction in constant volume condition. The effect was appeared at 5-10 minutes and complete inhibition was observed for 20-50 minutes. When recovery appeared, frequency of contraction (22±4.2 /h) and maximum contraction pressure (32±2.4 cmH2O) was same as control. Naftopidil (1.0 mg/kg, i.v.) increased the latency of bladder contraction for 180±12 % in single cystometrogram (CMG, n=3). Intercontraction interval was prolonged to 210±15 % when we used continuous CMG (n=4).

A B CNaftopidil Recovery control (0.97 mg/kg) (30 min.)

30cmH2O

1

0

Figure: Naftopidil inhibited the neural discharge (ND) and post discharge (PD).1: vesical pressure, 2: rate meter recording of the neural discharge (spikes/sec). In single unit-recording, pressure stimulation of urinary bladder using the saline injection produced the neural discharge (ND). ND detected at 20-30 cmH2O increased as vesical pressure increased (128-235 spikes/sec). ND immediately disappeared when vesical pressure returned to 0 cmH2O from the 30 cmH2O. When over use of the pressure stimulation, discharge was remained after decreasing the vesical pressure (post-discharge; PD). PD was not observed in control. Naftopidil (1.5 mg/kg i.v.) reduced or diminished the ND and recovery was observed in 30-60 minutes. It also inhibited the PD. Naftopidil (1.0 mg/kg) did not alter the carotid arterial pressure (120±7 mmHg).

127 2

0

2 min. ND PD


In addition, we tried acetic acid (0.1%, AA) infusion into the urinary bladder as the interstitial cystitis model (n=3). AA infusion shortened the latency of micturition reflex (LMR, 7.2 to 5.1 minutes) resulted from increasing the afferent activity (320±20 %). Naftopidil reversed the AA effects to the control (89% and 102%, LMR and ND respectively). AA infusion unmasked PD which abolished by naftopidil. Tamsulosin (0.0001 and 0.001 mg/kg i.v.) diminished the ND (0-7.1 %) and recovery was observed in 25-45 minutes. When recovery appeared, frequency of contraction and maximum contraction pressure was same as control. Unexpectedly, tamsulosin did not inhibit the PD. Larger dose of tamsulosin (0.01mg/kg i.v.) reduced the ND partially (78±2.5 %). Obvious recovery was not observed. When tamsulosin (0.01 mg/kg) did not act on the micturition-related discharge, naftopidil (1.5 mg/kg) completely inhibited these discharge and recovery was observed in 82±10 minutes (n=3). These data indicated larger dose of tamsulosin might have another effects. Interpretation of results Alpha-1 receptor antagonists inhibit the pressure-dependent ND of the vesical afferent. PD was inhibited with naftopidil but not with tamsulosin. Previous studies indicated naftopidil has selective affinity for alpha-1D adrenoceptor and tamsulosin has for alpha-1A adrenoceptor. Since PD was observed with inflammation of the uroepitherium and nearby structure, alpha-1D receptors might activate during the pathological condition. Concluding message Alpha-1D antagonist might be useful to treat the irritative symptoms in overactive bladder. References 1. Sugaya, K., Nishijima, S., Miyazato, M., Ashitomi, K., Hatano, T., Ogawa, Y.: Effects of intrathecal injection of

tamsulosin and naftopidil, alpha-1A and alpha-1D adrenergic receptor antagonists, on bladder activity in rats. Neuroscience Letters 2002, 328: 74-76

81 Cruz F1, Cruz C 2, Charrua A2, Avelino A 2, McMahon S B3

1. Dept. of Urology, Hospital de S. João, Porto, Portugal, 2. Institute of Histology and Embryology, Faculty of Medicine of Porto, and IBMC, Porto, Portugal, 3. Sensory Function Group, Centre for Neuroscience Research, London, United Kingdom SPINAL CORD PHOSPHORYLATION OF EXTRACELLULAR SIGNAL-REGULATED KINASES (ERKS) IS INDUCED BY SENSORY INPUT CONVEYED IN CAPSAICIN-RESISTANT BLADDER AFFERENTS AND CONTRIBUTES TO PAIN AND BLADDER REFLEX OVERACTIVITY IN A CHRONIC CYSTITIS RAT MODEL Hypothesis / aims of study The mitogen activated protein kinase (MAPK) is a family of serine/threonine protein kinases that transduce extracellular stimuli into post-translational and transcriptional responses [1]. This family is composed of several members such as extracellular signal-regulated kinases 1 and 2 (ERKs1/2), p38, c-Jun N-terminal kinase/stress-activated protein kinase (JNK/SAPK) and ERK5 [1]. In the spinal cord noxious stimuli induce rapid ERKs 1/2 phosphorylation in second order sensory neurones. In rats, inhibition of ERKs phosphorylation results in reduction of acute pain behaviour [1]. The occurrence of ERKs phosphorylation in the spinal cord after chronic bladder inflammation, a well-known cause of pain and increased bladder reflex activity [2,3], is undetermined. In this study, we investigated (i) spinal ERKs phosphorylation after innocuous and noxious distension of intact and inflamed bladders, (ii) which bladder afferents convey nociceptive input responsible for ERKs phosphorylation and (iii) the role of ERKs activation in bladder reflex activity.

Study design, materials and methods Bladders of intact and cyclophosphamide (CYP)-inflamed rats (75mg/kg i.p. once every 3 days during 10 days) were distended at 15 (innocuous) or 60 cm H2O (noxious) for 2 minutes. After immediate perfusion, spinal cord segment L6 was removed, post-fixed and 40 µm transverse sections immunoreacted with a specific antibody raised against phosphorylated ERKs. Immunoreactive (IR-) cells were counted in 10 sections/animal and averaged.


To identify bladder afferents conveying sensory input responsible for ERKs phosphorylation, intact and inflamed animals were treated intravesically with either resiniferatoxin 100nM (RTX) or its vehicle. On the following day rats were submitted to bladder distension for 2 minutes at 60 and 15 cm H2O, respectively. As above, animals were immediately perfused and L6 segment analysed. To evaluate the role of spinal ERKs phosphorylation in bladder reflex activity, intrathecal catheters were implanted at L6 spinal level. Three days later, animals were i.p. injected with either saline or CYP (200 mg/Kg). Four hours later, animals were anaesthetised with urethane and bladders exposed. After bladder stabilization, cystometrograms were obtained while saline was infused (6ml/h) through the dome. The urethra remained open and body temperature maintained at 36-37ºC. The frequency of bladder contractions was determined while saline, 1 and 5 µg of PD98059 (a specific ERKs phosphorylation inhibitor) were injected intrathecally.

Results Scarce IR-cells were observed in sections from non-stimulated intact (1.5±0.58) or inflamed animals (1.75±0.96). Bladder stimulation at 15 cmH2O induced low ERKs phosphorylation in intact animals (8.75±1.71) and strong activation in inflamed rats (21.13 ± 6.61; p<0.001, against intact animals). Bladder distension at 60 cm H2O significantly increased ERKs phosphorylation in both intact (30.95±3.46; p<0.001) and inflamed rats (41.13 ± 2.63; p<0.001). Inflamed animals had, however, significantly more IR-cells (p<0.01) than intact animals. In all experiments, IR-cells were bilaterally distributed in laminae I-II, lamina X and intermediolateral grey matter. Desensitization of capsaicin-sensitive bladder afferents by intravesical RTX did not affect ERKs phosphorylation induced by bladder distension in both intact and inflamed rats. Intact animals had 0.50±0.07 bladder contractions/minute which was not changed by intrathecal 1 or 5 µg of PD98059. In inflamed animals bladder contractions/minute were 0.94±0.33 /minute (p<0.05 against intact animals). Intrathecal 1 µg reduced bladder reflex activity to 0.66±0.25/minute (p<0.05). Although 5 µg further reduced bladder frequency to 0.52±0.20/minute, this decrease was not significantly different from that obtained after 1 µg PD98059. Interpretation of results This study shows that ERKs activation participates in bladder pain perception in both intact and inflamed animals and may contribute to allodynia in inflammatory bladder conditions. As ERKs phosphorylation is not affected by C-fibre desensitization by RTX, this study suggests that bladder sensory input leading to ERKs phosphorylation in the spinal cord is conveyed by capsaicin-resistant, presumably Aδ fibres. Furthermore, ERKs activation has a specific role in regulating bladder reflex hyperactivity associated to inflammatory states. Concluding message Since ERKs inhibition by intrathecal PD98059 decreased bladder reflex activity in inflamed but not in intact animals, this study forwards that ERKs inhibitors may be relevant to treat allodynia and increased micturition frequency associated to chronic bladder inflammation. FUNDING: Funded by grant SFRH/BD/2001/5826, FCT/PGDB and FCT project POCTI/32466/NSE/2000,Portugal. 82 Nishijima S1, Sugaya K1, Miyazato M1, Chinen Y1, Morozumi M1, Ogawa Y1

1. Department of Urology, Faculty of Medicine, University of the Ryukyus. MICTURITION INHIBITORY MECHANISM OF THE ROSTRAL PONTINE RETICULAR FORMATION AND THE SPINAL GLYCINERGIC NEURONS IN RATS WITH OR WITHOUT CEREBRAL INFARCTION Aims of study In the central nervous system (CNS), glutamate which is the major excitatory amino acid plays a role in the facilitation of bladder contractions, and gamma-amino butyric acid (GABA) inhibits micturition reflex activity. Glycine has been also identified as another important inhibitory neurotransmitter in the CNS, and intrathecal injection of glycine inhibits bladder contractions. Recently, it has been reported that injection of a cholinergic


agent into the rostral pontine reticular formation (RPRF) induced atonia and the increase of the spinal glycine level in cats. In rats, injection of carbachol (a cholinergic agent) or flavoxate hydrochloride into the RPRF inhibited bladder contractions and increased the spinal glycine levels. In our previous study, the spinal glycine level significantly decreased at acute term after cerebral infarction (CI) in rats with urinary frequency, but urinary frequency improved and the spinal glycine level recovered to the baseline level at 2-4 weeks after CI. Therefore, in order to clear the role of the RPRF for lower urinary tract function in intact CNS and CI conditions, we examined the effect of RPRF stimulation on bladder activity and the spinal glycine level in rats with or without CI. Materials and methods Fifty female Sprague-Dawley rats were used. The rats were divided into four groups; 1) 10 intact rats for cystometry, 2) 15 intact rats for amino acid analysis, 3) 10 CI rats for cystometry, and 4) 15 CI rats for amino acid analysis. Rats from the CI group were anaesthetized with 2% halothane, and a 4-0 nylon thread was inserted into the right middle cerebral artery to make CI. At 3 days after surgery, intact and CI rats were anaesthetized with urethane, and a small hole was made in the cranial born (bregma -9.5 mm, R 1.0 mm). In 20 rats for cystometry, a polyethylene catheter was inserted into the bladder through the urethra. The urethra was ligated to the catheter near the external urethral meatus, and bladder was filled with physiological saline (0.05 ml/min) to above the threshold volume to induce isovolumetric rhythmic contractions. After the bladder contractions had become stable, 0.5 µl of physiological saline, carbachol (0.3 µM) and flavoxate chloride (0.3 or 3 µM) were injected into the RPRF by a microsyringe, and the change of bladder activity was recorded. In 30 rats for amino acid analysis, 0.5 µl of physiological saline, carbachol (0.3 µM) and flavoxate chloride (0.3 or 3 µM) were injected into the RPRF. After 5 min, these rats were sacrified and the spinal glycine level was measured. Data were expressed as means±standard deviation. Results In intact rats, injection of physiological saline did not influence any parameters of bladder contractions and the spinal glycine level. When carbachol (0.3 µM) was injected, bladder contractions disappeared over 30 min and the spinal glycine level was significantly increased (44% increase compared with controls). Injection of flavoxate (0.3 µM) also transiently abolished bladder contraction for 12.4±3.3 min, and the spinal glycine level was significantly increased (29% increase compared with controls). In CI rats, the frequency and amplitude of bladder contractions were significantly increased (69% and 56% increase, respectively), while the spinal glycine level was significantly decreased (34% decrease) compared with those in intact rats. When carbachol was injected, bladder contractions were transiently abolished, but bladder contractions were recovered after 10 min. The spinal glycine level did not change after carbachol injection. Injection of physiological saline and flavoxate (0.3 µM) did not influence any parameters of bladder contractions and the spinal glycine levels. However, high dose of flavoxate (3 µM) transiently abolished bladder contractions for 4.9±1.3 min although the spinal glycine level did not change. Interpretation of results In intact rats, activation of the RPRF by local injections of carbachol or flavoxate may inhibit the micturition reflex by activation of spinal glycinergic neurons. In CI rats with urinary frequency, the spinal glycine level was decreased compared with intact rats. The effects of injections of carbachol or flavoxate into the RPRF on bladder activity and the spinal glycine level were weaker in CI rats than intact rats. These results suggest that activity of the RPRF is weak in CI rats, and that weak activity of the RPRF is due to the decrease of excitatory projection from the upper CNS to the RPRF after CI. Concluding message Urinary frequency after cerebral vascular diseases may be due to the decrease of excitatory projection from the upper CNS to the RPRF in addition to the decrease of inhibitory projection to the pontine micturition center. The RPRF plays an important role in the inhibition of the micturition reflex by activation of spinal glycinergic neurons.


83 Finazzi Agro E1, Brusa L2, Petta F1, Miano R1, Zuccalà A1, D'Amico A3, Stanzione P2

1. Dept. of Urology, Tor Vergata University, 2. Dept. of Neurology, Tor Vergata University, 3. IRCCS S. Lucia Hospital THE ROLE OF DOPAMINE RECEPTORS ON LOWER URINARY TRACT FUNCTION IN PARKINSON’S DISEASE PATIENTS Hypothesis / aims of study The different role of D1 and D2 dopamine receptors on lower urinary tract (LUT) behavior has been demonstrated in few animal studies. In particular, Seki et al. showed that D2 selective agonists and D1 selective antagonists produce a reduction of the bladder capacity and of the volume threshold for the micturition reflex in conscious rats (1). Thus, the author concludes that D2 receptors could be involved in the facilitation of micturition reflex, while D1 could exert a tonic inhibition of bladder voiding. This finding has never been confirmed in human studies. Thus, the aim of our study was to investigate the role of D1 and D2 agonists/antagonists on LUT behavior in Parkinson’s disease (PD) patients. Study design, materials and methods 13 patients (5 females, 8 males), after signing an informed consent, were evaluated. Mean age was 61± 7.32 years. All patients were affected by idiopathic PD according with the Brain Banck Criteria (2) with an Hohen and Yahr score lower than 2.5 and a mean disease duration of 3.5 ± 1.3 years. UPDRS(section III) mean score in off condition was 32.34 ± 3.6. All subjects presented with overactive bladder symptoms. Patients were evaluated with urodynamic studies performed in four conditions: in off status (therapy withdrawal since at least 7 days if treated with L-DOPA (LD) agonists or 21 days if treated with LD); 45 minutes after oral administration of 250 mg of LD (D1-D2 agonist); 45 minutes after simultaneous administration of 250 mg oral LD and 20 mg Domperidone (D2 peripheral antagonist); 45 minutes after simultaneous administration of 250 mg oral LD and 150 mg intramuscular Sulpiride (D2 central antagonist). No patient was assuming drugs with effects on LUT. Urodynamic evaluation was constituted by a 50 ml/min filling cystometry followed by a pressure/flow study with perineal floor EMG. The following urodynamic parameters were evaluated: first sensation of bladder filling, detrusor neurogenic overactive contractions (DNOC) threshold and amplitude, bladder capacity, maximum flow (Qmax), detrusor pressure at maximum flow (Pdet@Qmax), post-void residual urine, presence of detrusor/sphincter pseudodyssynergia (DSPD). Results obtained in the four previously specified conditions were collected and statistically compared by means of ANOVA test and post-hoc Tukey test. Results

Mean (SD) Pats.=13 Off LD p+ LD+Dom p* LD+Sul p* First sensation (ml) 130 (55) 110 (75) ns 125 (78) ns 216±85 0.006 DNOC threshold (ml) 255 (140) 168 (104) 0.07 175 (112) ns 310±78 0.03 DNOC amplitude (cmH2O) 66 (39) 76 (41) 0.07 73 (39) ns 48±36 0.01 Bladder capacity (ml) 347 (125) 269 (105) 0.02 283(111) ns 412±94 0.04 Q max (ml/s) 17 (9) 17 (6) ns 17 (5) ns 16 (6) Ns Pdet@Qmax (cmH2O) 38 (19) 48 (28) ns 47 (25) ns 41 (20) Ns Residual urine (ml) 11 (21) 7 (5) ns 12 (8) ns 13 (28) Ns DSPD (y/n) 2/11 2/11 - 2/11 - 2/11 -

Legend: Dom: Domperidone; Sul: Sulpiride; +LD vs. Off status; * LD+Dom and LD+Sul vs. LD. Interpretation of results The administration of a D1/D2 agonist (as LD) seems to produce a worsening of neurogenic detrusor overactivity; the same result is obtained when a peripheral D2 antagonist as Domperidone is given simultaneously. On the other hand, the administration of a D2 central antagonist as Sulpiride seems to reverse the effect of LD, with non significant improvement in comparison to off status. Concluding message Our study seems to confirm that D2 receptors of the central nervous system could be involved in the facilitation of micturition reflex in human as well as what found in animal models. References Neurourol Urodyn. 2001;20(1):105-13. 2. J Neural transmission, 39 (Suppl): 165-172, 1993.


84 Dalmose A L1, Bjarkam C R2, Djurhuus J C1

1. Institute of Experimentel Clinical Research, The University of Aarhus, Denmark, 2. Institute of Anatomy, The University of Aarhus, Denmark THE PONTINE MICTURITION CENTRE IN THE PIG. Hypothesis / aims of study Fluoroscopy and MRI can be used without modifications in chronic studies in pigs enabling monitoring of the positioning of equipment implanted by stereotactic procedures. In order to advance the use of pigs in the neurophysiology we aimed at localising a pontine micturition center by recording of pressures in the lower urinary tract during stereotactic stimulation by a needle-electrode in the pontine region. Study design, materials and methods The pigs were intubated and placed in a prone position and kept on an isoflurane inhalation anesthesia. The head of the pig was fixated in a stereotactic frame by bilateral bone-screws inserted into the zygomatic arc directly below the lateral margin of the eye. A 3 by 5 cm hole was made in the skull giving access to the sinus frontalis, which in adult pigs is a 2 to 5 mm cavity that stretches almost to the line where the trapezoid muscle inserts. A 2 by 3 cm hole made in the floor of the sinus frontalis, giving access to the dura, which was cut open, and the brain. A tungsten needle electrode was inserted for the stimulations. For pressure recording in the urethra independent from the bladder a transurethral separation catheter was inserted. Results A total of 10 pigs with a weight of 30 to 70 kg were examined. Repeated fluoroscopic visualization of the needle electrode relative to the rete mirabilis was performed in the early 3 pigs until stereotactic coordinates were established. Stereotactic mapping was performed in 1 mm steps in all 3 planes. In 8 pigs one or two types of pressure responses in the lower urinary tract to stimulation of the brainstem were recorded. The responses were: a) changes similar to voiding, i.e. urethral pressure decrease followed within less than 1 s by a bladder pressure increase, or b) changes similar to a continence response, i.e. urethral pressure increase and no change in bladder pressure. These responses could be evoked from distinct areas in the pontine region, in few cases directly adjacent to one-another. Flouroscopy, MRI-scans and histological specimens demonstrated the electrode-tip positioned in the pons.

Figure 1. MRI-scan, sagittal view (the spine going caudally to the right at the bottom of the picture), of a pig brain. Four thin arrows mark the electrode; fat arrow marks the vascular formation rete mirabilis anterior to the pons. (Whitening of the anterior part of the brain and the distorsion of the upper part of the electrode are artefacts).


Interpretation of results In this study in the pig we reproducibly demonstrated areas in the pontine region capable of evoking either voiding or continence responses in the lower urinary tract. The brain of the pig is much larger than that of cats and rats, and the pathways involved in the regulation are formed by larger numbers of neurons and therefore studies in pigs may lead to more accurate information on neurotransmitters and pathways. The needle location in areas responsible for voiding and continence responses could be visualized by MRI and fluoroscopy, and accordingly the pig appears to be feasible also for chronic stereotactic studies. Concluding message Demonstration of a pontine micturition centre in the pig has interesting advantages as information of high accuracy about the neuro-regulation and information from chronic studies can be obtained. FUNDING: The Mads Clausen Foundation, The Sahva Foundation, The University of Aarhus 85 Finazzi Agro E1, Petta F1, Brusa L2, Miano R1, D'Amico A3, Parisi I3, Stanzione P2

1. Dept. of Urology, Tor Vergata Univ, 2. Dept. of Neurology, Tor Vergata Univ, 3. IRCCS S. Lucia Hospital EFFECTS OF L-DOPA ON URODYNAMIC FINDINGS IN PARKINSON’S DISEASE PATIENTS: ACUTE VS. CHRONIC ADMINISTRATION Hypothesis / aims of study Several studies on the urodynamic effects of L-DOPA (LD) on lower urinary tract (LUT) behavior in Parkinson’s disease (PD) patients have been published. Unfortunately, these studies show divergent results, with some of them affirming that LD reduces the severity of detrusor overactivity (DO) (1), while others found the opposite (2). Aim of our study was to compare the effects of LD on urodynamic findings in PD patients, after acute and chronic administration. Study design, materials and methods 13 patients (5 females, 8 males), after signing an informed consent, were evaluated. Mean age was 61± 7.32 years. All patients were affected by idiopathic PD according with the Brain Banck Criteria (3) with an Hohen and Yahr score lower than 2.5 and a mean disease duration of 3.5 ± 1.3 years. UPDRS(section III) mean score in off condition was 32.34 ± 3.6. All subjects presented with overactive bladder symptoms. Patients were evaluated with urodynamic studies performed in three conditions: in off status (therapy withdrawal since at least 4-5 days if treated with LD agonists or 21 days if treated with LD); 45 minutes after oral administration of 250 mg of LD to evaluate patients during the drug “best on” (acute administration, LD acute); after one month of treatment with LD (mean daily dose 557± 158 mg ) (chronic administration, LD chronic). No patient was assuming drugs with effects on LUT. Urodynamic evaluation was constituted by a cystometry followed by a pressure/flow study with perineal floor EMG. The following urodynamic parameters were evaluated: first sensation of bladder filling, detrusor neurogenic overactive contractions (DNOC) threshold and amplitude, bladder capacity, maximum flow (Qmax), detrusor pressure at maximum flow (Pdet@Qmax), post-void residual urine, presence of detrusor/sphincter pseudodyssynergia (DSPD). Results obtained in the three previously specified conditions were collected and statistically compared by means of ANOVA test and post-hoc Tukey test. Results

Mean (SD) Mean (SD) Pats.=13 Off status LD Acute p+ LD Chronic P* First sensation (ml) 130 (55) 110 (75) ns 241 (94) <0.01 DNOC threshold (ml) 255 (140) 168 (104) =0.07 307 (138) ns DNOC amplitude (cmH2O) 66 (39) 76 (41) =0.07 55 (34) =0.03 Bladder capacity (ml) 347 (125) 269 (105) =0.02 360 (126) ns Q max (ml/s) 17 (9) 17 (6) ns 16 (6) ns Pdet@Qmax (cmH2O) 38 (19) 48 (28) ns 41 (20) ns Residual urine (ml) 11 (21) 7 (5) ns 13 (28) Ns DSPD (y/n) 2/11 2/11 - 2/11 -

Legend: +LD Acute vs. Off status; * LD Chronic vs. Off status.


Interpretation of results According to our findings, acute LD administration seems to produce a worsening of neurogenic detrusor overactivity, with a significant decrease of bladder capacity and a (not significant) worsening of DNOC threshold and amplitude; on the other hand, chronic LD administration does not affect bladder capacity, but seems to provoke an improvement of some urodynamic parameters of the filling phase (first sensation, DNOC amplitude). No clear effect of LD administration could be demonstrated on voiding phase parameters. Concluding message The controversial data present in the literature could be due to different ways of LD administration (and/or of pre-evaluation drug withdrawal). It is interesting to observe that, if LD acute administration seems to worsen neurogenic detrusor overactivity of PD patients, its chronic administration produces an improvement of some urodynamic parameters: this finding could explain the clinical benefit on urinary symptoms often reported by the patients during chronic treatment. References

1) Neurourol Urodyn, 12: 203-209, 1993. 2) Neurourol Urodyn, 19: 540, 2000 3) J Neural transmission, 39 (Suppl): 165-172, 1993.

86 Achtari C1, McKenzie B2, Briggs C2, Rosamilia A1, Dwyer P1

1. Mercy Hospital for Women, 2. Department of anatomy and cell biology AN ANATOMICAL STUDY OF THE OBTURATOR CANAL AND DORSAL NERVE OF THE CLITORIS AND THEIR RELATIONSHIP TO TRANSOBTURATOR SLINGS Hypothesis / aims of study Use of synthetic suburethral slings has simplified the treatment of urinary stress incontinence. Complications after TVT® and SPARC® procedures, which penetrate the retro-pubic space include bladder, minor and major blood vessel (obturator or iliac) and bowel perforation. Recently, a transobturator route of insertion of suburethral slings has been described avoiding the retro-pubic space. Although occasional bladder perforations have been reported, this new approach avoids the risk of bowel and allegedly of major vessel perforation. Several devices have been developed using an “out-in” (Monarc®) technique whereas one (TVT-O®) is inserted from inside-out. The dorsal nerve of the clitoris runs along the internal surface of the ischio-pubic ramus in Alcock’s canal and could potentially be at risk from transobturator devices. The obturator vessels and nerve with their anterior and posterior divisions could also be at risk. The aim of this anatomical study is to compare the distance between the different devices for the treatment of stress incontinence, and the dorsal nerve of the clitoris and the obturator canal. Study design, materials and methods We performed a dissection of the dorsal nerve of the clitoris from its origin from the pudendal nerve and followed its course in Alcock’s canal to the point where it crosses the inferior margin of the pubic bone on 5 embalmed hemipelves. We also prepared the obturator externus muscle and the obturator canal with its contents. Four procedures were performed on each specimen reproducing the actual way of insertion of each device. Tapes were not attached. The shortest distance between each device needle and the dorsal nerve of the clitoris was measured. The distance to the obturator canal was measured from the needle to the centre of the internal os for the TVT® and SPARC®, and to the centre of the external os for the Monarc® and TVT-O®.


Results

Dorsal nerve of clitoris Obturator canal

Median (Range) Mean +/- Std Dev Median (Range) Mean +/- Std Dev

TVT ® 16 mm (12 – 22) 16.2 +/- 4.4 mm 40 mm (35 – 44) 40 +/- 3.4 mm

SPARC ® 15 mm (11 – 19) 15.2 +/- 3.0 mm 41 mm (35 – 43) 40.2 +/- 3.1 mm

Monarc ® 15 mm (10 – 16) 13.8 +/- 2.7 mm 25 mm (22 – 30) 25.2 +/- 2.9 mm

TVT-O ® 14 mm (10 – 15) 13.2 +/- 2.2 mm 20 mm (17 – 23) 19.6 +/- 2.3 mm Dissection of 5 further hemipelves is currently being performed which includes fresh frozen specimen dissections. A description of the dorsal nerve of the clitoris with its variations will be provided. In addition the relationship of the passage of the devices to the clitoris including the crura will be described. A demonstration of the potential risk to the clitoris and its nerve by prepubic passage of TVT will also be provided. Interpretation of results The distance between the different devices and the dorsal nerve of the clitoris are similar. In this study, the TVT-O device is 5 mm closer to the obturator canal than the Monarc needle. However, the clinical significance of this is unknown. It is possible that these distances are altered by the dissection process and for that reason fresh frozen dissection will be carried out. Concluding message Based on our initial series of embalmed cadaveric dissection, transobturator devices are at least 10 mm away from the dorsal nerve of the clitoris. These distances refer to the introducing needle. The tape width is 10 mm and may therefore be closer to the structures in question. The TVTO ® needle crosses the obturator foramen somewhat closer to the obturator canal than the Monarc ®. In addition to anatomical studies, the potential clinical sequelae of involvement of the dorsal nerve of the clitoris or branches of obturator vessels and nerve need to be investigated. 87 Mahajan S 1, Elkadry E2, Kenton K1, Shott S 3, Brubaker L1

1. Loyola University Medical Center, 2. Mt. Auburn Hospital, 3. Rush University Medical Center PATIENT SELECTED GOALS: PERSPECTIVES ON SURGICAL OUTCOMES ONE YEAR AFTER SURGERY Hypothesis / aims of study To assess the relationship between patient selected surgical goals, objective outcomes and patient satisfaction 1 year after pelvic reconstructive surgery. Study design, materials and methods After IRB approval, an independent physician investigator contacted 78 female patients approximately 1 year after undergoing pelvic reconstructive surgery. We have previously reported the objective success, goals and expectations of this group of patients 3 months after surgery (reference 1). After deciding to proceed with surgery and surgical informed consent was obtained; patients were approached for study participation. Prior to surgery, participants were contacted by phone by a single investigator, not the primary surgeon, who asked the patient to list her goals for surgery. Goals were clarified, but were not removed even if they were unreasonable after patients were counselled and their questions answered. Peri- and post-operative care was performed in accordance with routine clinical practice. All patients underwent a


standardized post-operative examination 13 weeks after surgery, including prolapse quantification and a standing dual-channel cystometrogram. Persistent urodynamic stress incontinence was diagnosed if any transurethral urine loss occurred in the absence of detrusor contraction. Objective cure of prolapse was defined as < Stage 1 support. Anything else was considered a failure. All patients were contacted via telephone by the original investigator 12 to 15 weeks after surgery to assess patient perceptions of goal achievement and the surgical experience using a standardized interview format. Any symptomatic complaints of de novo or persistent detrusor overactivity with or without incontinence were treated as part of routine clinical practice. In this follow-up study, patients were contacted via telephone by a second investigator a mean of 15.3 months after surgery. This investigator was aware of their self-identified pre-operative goals for surgery, but blinded to patients’ procedures, past surgical history, and three-month post-operative assessment of goal achievement until all 1-year follow-up interviews were completed. Patient perceptions of goal achievement, satisfaction, and the surgical experience were again assessed using the same standardized interview format that had been previously utilized. Achievement of a goal was defined as patient self-description of goal completion as a 4 or 5 on a 5-point Likert scale. Current feelings of pain, fatigue, and depression one year after surgery were assessed using a 5-point Likert scale. Reasons for failure to attend a one-year post-operative follow-up visit were also assessed. Statistical analysis was performed using SPSS (SPSS, Chicago, IL). Data was analyzed using the Spearman correlation, the chi-square test of association, and the Friedman test. Results Seventy-eight women participated in the original study. Seventy-one (91%) participated in the second interview. Of the seven patients lost to follow-up, 4 declined to participate and 3 could not be reached by telephone. Patient satisfaction ratings at one year after surgery were not statistically different from ratings at 3 months after surgery (P=0.396). Patient satisfaction at 3 months and 1 year after surgery was associated with the achievement of self-selected goals (P<0.0005). The number of patient goals achieved did not change significantly from 3 months to 1 year after surgery (P=0.505). Objective cure of prolapse was associated with greater satisfaction 1 year post-operatively (P=0.006), while objective cure of incontinence was not related to satisfaction (P=0.602). Persistent or de novo detrusor over activity occurred in 52.6% of patients. Post-operative detrusor overactivity was predictive of lower rates of patient satisfaction (P=0.041). The perception of surgery as a success was positively associated with both patient achievement of surgical goals (P=0.013) and satisfaction (P<0.0005) at 1 year post-operatively. Patient perception of having had a surgical complication at 3 months post-operatively was positively associated with perceived complications at 1 year after surgery (P=0.010). However, patients often perceived common peri-operative conditions to be complications, including urinary tract infections (11), post-operative pain (7), and discharge home with a catheter (9). Interpretation of results Patient long-term satisfaction 1 year after surgery was accurately predicted by short-term satisfaction 3 months after surgery. Patient satisfaction was dependent upon the perceived achievement of subjective goals and less consistently on traditional objective measures of success. Patient satisfaction was strongly correlated with objective cure of prolapse, but not with the objective cure of incontinence. Complaints of detrusor overactivity, de novo or persistent, consistently adversely affect patient satisfaction regardless of whether objective success was achieved. Concluding message Symptoms of detrusor overactivity and failure to achieve self-selected subjective surgical goals adversely affect patient perceptions of surgical success, independent of physician assessments of objective success. Short-term assessments of patient satisfaction are associated with patient long-term satisfaction after surgery. References 1Patient-selected goals: A new perspective on surgical outcome. American Journal of Obstetrics and Gynecology. 189(6):1551-7; discussion 1557-8, 2003 Dec.


88 Heit M1, Blackwell L 1, Kelly S2

1. Urogynecology Specialists of Kentucky, PLLC, 2. University of Louisville MEASURING PATIENT EXPECTATIONS FOR INCONTINENCE CARE SEEKING Hypothesis / aims of study Meeting patient expectations may be the quickest way to achieve patient care satisfaction, independent of health outcomes. Patient expectations may differ for a racially heterogeneous female incontinent population. Therefore it would be essential to identify race-specific expectations of incontinence care seeking if physicians hope to provide satisfying incontinence care. An incontinence-specific expectation measurement tool has not been developed or validated to operationalize an expectation variable. The objective of this study is to establish the structure and factor validity of an expectation questionnaire and estimate its reliability in a racially heterogeneous incontinent female population. Study design, materials and methods Racially diverse continent focus group participants (n=55) were asked, open-ended questions about their expectations regarding outcomes, advantages and disadvantages of either seeking incontinence care promptly or adopting a wait and see approach. Video and audio taping equipment were used to transcribe a script of the proceedings for review by the principal investigator (MH) and qualitative sociologist (SK) in preparation for a thematic analysis. The themed analysis included an 1) independent review of the interview data for commonly reported themes in response to focused questions, 2) independent generation of themes for expected outcomes, advantages and disadvantages of seeking prompt care or adopting a wait and see approach, 3) collaborative identification of categories of responses that represent the newly generated themes. From this preliminary research, one questionnaire on the perceived likelihood of good or bad outcomes of care seeking for incontinence (expectations) was developed. Racially diverse incontinent focus group participants (n=63) were administered the 21-item questionnaire to refine its wording prior to conducting computer assisted telephone interviews (CATI). CATIs were conducted on a nonprobability sample of 275 incontinent females (95 Caucasian, 95 African American, 80 Hispanic, 5 Other). Study participants were asked to assess the likelihood of a specific outcome of incontinence care seeking from 1 (not at all likely) to 10 (definitely). A principal components exploratory factor analysis (Varimax rotation) was performed to estimate the factor loadings (Eigenvalues > 1) of the 21 item questionnaire. A confirmatory factor analysis was conducted to establish the final structure of the expectation questionnaire and assess its fit in our racially diverse incontinent female population. Cronbach’s alpha coefficients were estimated to establish the reliability of the final expectation questionnaire and its subscales. Results Four factors explained 42.7% of the variance on the 21 item questionnaire. In the final model, 6 good outcome items loaded on a control factor (factor loadings 0.502-0.806). The two expectation items with the highest loadings on the control factor were “I would be able to resume my normal activities,” (r = 0.806) and “I would regain control of my life.” (r = 0.726). Four bad outcome items loaded on an internalized fear/anxiety factor (factor loadings 0.449-0.497). The two expectation items with the highest loadings on the internalized fear/anxiety factor were “I would be told it was caused by something I had done in my past,” (r = 0.485) and “I would be labelled a hypochondriac.” (r = 0.497). Two 2 bad outcome items loaded on an externalized fear/anxiety factor (factor loadings 0.553-0.726). The two expectation items with the highest loadings on the externalized fear/anxiety factor were “I would be referred to a specialist,” (r = 0.553) and “my doctor would tell me I needed surgery (r = 0.726). A CMIN/DF of 1.70, GFI of 0.95, CFI of 0.95, and a RMSEA of 0.050 (P CLOSE 0.463) established the fit of our final expectation questionnaire. Cronbach’s alpha coefficient for the final 12 item expectation questionnaire was 0.56 (Control subscale 0.82, internalized fear/anxiety subscale 0.53, and externalized fear/anxiety subscale 0.57). Interpretation of results The 12-item expectation questionnaire is a valid and reliable tool for measuring expectations for incontinence care seeking. It can be used to measure expectations in a racially heterogeneous incontinent female population.


Concluding message Race-specific expectations of incontinence care may differ and can be potentially modified to increase the percentage of women who receive satisfactory incontinence care when sought. (Supported by NICHD R03 HD-00-012) FUNDING: National Institute of Child and Human Development 89 Heit M1, Blackwell L 1, Kelly S2

1. Urogynecology Specialists of Kentucky, PLLC, 2. University of Louisville MEASURING BARRIERS TO INCONTINENCE CARE SEEKING Hypothesis / aims of study Health disparities in a heterogeneous population can partially be explained by differences in access to quality healthcare. Incontinent female Hispanics and Non-Hispanic African Americans may have unique barriers to incontinence care to which Caucasians remain unexposed. Barriers are specific, objective, external conditions that prevent someone from seeking care. Yet a incontinence-specific barrier measurement tool has not been validated to operationalize a barrier variable. The objective of this study was to establish the factor validity of a modified Melnyck’s Barrier Scale and estimate its reliability in a racially heterogeneous incontinent female population. Study design, materials and methods Melnyk’s Barriers Scale was developed to operationalize the concept of barriers as the consumer’s perceptions of cost or obstacles to care. The 19-item modified Melnyk’s Barrier Scale was constructed from 3 items with the highest loadings on the relationship factor, 2 items with the highest loadings on the site-related factor, 3 items with the highest loadings on the cost factor plus 3 items from the incontinence medical literature which were hypothesized to load on the cost factor, 3 items with the highest loadings on the fear factor, and 2 items with the highest loadings on the inconvenience factor plus 3 items from the incontinence medical literature which were hypothesized to load on the inconvenience factor. Racially heterogeneous incontinent focus group participants (n=63) were administered the 19-item questionnaire to refine its wording prior to conducting computer assisted telephone interviews (CATI). CATIs were conducted on a nonprobability sample of 275 incontinent females (95 Caucasian, 95 African American, 80 Hispanic, 5 Other). Study participants were asked to rate the degree to which barrier items affected their seeking medical care for incontinence on a 4-point Likert scale ranging from 0 (none) to 3 (greatly). A confirmatory factor analysis was conducted to confirm the structure of the modified Melnyk’s Barrier Scale and assess its fit in our racially heterogeneous incontinent female population. Cronbach’s alpha coefficients were estimated to establish the reliability of the final barrier measurement model and its subscales. Results Only 1 of 6 barrier items (“Office hours at the office or clinic are limited”) from the incontinence medical literature was retained in the model. This barrier item loaded on the inconvenience factor with a factor loading of 0.812. In the final model, the 14-item modified Melnyk’s Barrier Scale contained 3 items that loaded on the inconvenience factor (factor loadings 0.659-0.812). The barrier item with the highest loading (r = 0.812) on the inconvenience factor was “office hours at the office or clinic are limited.” Three items loaded on the relationship factor (factor loadings 0.452-0.796). The barrier item with the highest loading (r = 0.796) on the relationship factor was “the physician or nurse practitioner doesn’t take time to explain what he or she is doing or why, or answer my questions.” Two items loaded on the site-related factor (factor loadings 0.554-0.960). The barrier item with the highest loading (r = 0.960) on the site-related factor was “the office or clinic is too far away.” Three items loaded on the cost factor (factor loadings 0.481-0.891). The barrier item with the highest loading (r = 0.891) on the cost factor was “my insurance is too complicated to figure out.” Three items loaded on the fear factor (factor loadings 0.457-0.624). The barrier item with the highest loading (r = 0.624) on the fear factor was “I am afraid to find out I have a serious problem.” A CMIN/DF of 2.12, GFI of 0.93, CFI of 0.93, and a RMSEA of 0.064 (P CLOSE 0.060) established the fit of our final model. Cronbach’s alpha coefficient


for the final 14-item Modified Melnyk’s Barrier Scale was 0.828 (Inconvenience subscale 0.79, Relationship subscale 0.68, Site related subscale 0.69, cost subscale 0.71, fear subscale 0.57) Interpretation of results The 14-item modified Melnyck’s Barrier Scale is a valid and reliable tool for measuring barriers to incontinence care seeking. It can be used to measure barriers in a racially heterogeneous incontinent female population. Concluding message Race-specific barriers to incontinence care seeking are potentially modifiable which should increase the percentage of women who seek care thereby reducing health disparities between heterogeneous populations. (Supported by NICHD R03 HD-00-012) FUNDING: National Institute of Child and Human Development 90 Botros S1, Gandhi S1, Abramov Y1, Nickolov A2, Sand P1, Goldberg R1

1. Evanston Continence Center, Northwestern University,Feinberg School of Medicine, 2. Center on Outcomes, Research and Education, Evanston Northwestern Healthcare ARE INCONTINENT WOMEN FINDING THE HELP THEY SEEK? Hypothesis / aims of study Women with socially bothersome urinary incontinence face barriers to seeking or obtaining medical attention, often for personal reasons. One study determined in a cross-sectional survey of adult US women that only 38% of women with incontinence initiated a conversation with a physician.(1) In addition, urinary symptoms are often overlooked by healthcare providers on the primary care level. This abstract seeks to identify the characteristics of women with socially bothersome urinary incontinence, to determine what proportion of these women do not seek care and the reasons why. Conversely, we investigated characteristics of women who successfully obtained care and the factors that influenced them. Study design, materials and methods A 67- item questionnaire was administered to 374 female twins in Twinsburg, Ohio at the national twins’ convention. The survey included demographic information, detailed questions pertaining to urinary, fecal and sexual dysfunction as well as prolapse, the short forms of the UDI and IIQ, and whether or not patients were socially bothered by the respective issues. Additional survey questions asked whether patents raised the issue with their doctors, if doctors raised the issues with them, if they actually saw a physician regarding their problems, and their perceptions and reasons for not seeking care. Data were analysed using descriptive statistics, student t-tests and chi-squared tests for univariate analysis, and spearman’s coefficient for ordinal data. p values<0.05 were considered significant. Results Among 374 women surveyed, 58% reported stress, urge or mixed urinary incontinence, 11% reported fecal soiling, and 11% reported fecal incontinence. Thirty percent of women with incontinence reported socially bothersome incontinence. Forty-four percent of women with socially bothersome incontinence raised the issue with a physician. Table 1 summarises reasons why women did not seek care, and Table 2 describes symptoms associated with socially bothersome incontinence. Of note, 58% of women with ‘moderate to severe’ urge incontinence, based on the Likert scale, raised the issue of incontinence with a physician. When the same women were asked whether they had seen a doctor for their problem, 47% responded ‘no’. Similar results were found in women with stress incontinence. Of all women surveyed, only 13% (49) indicated that they successfully obtained medical care for symptoms of pelvic floor dysfunction. Of these women, half (53%) were ‘socially bothered’ by urinary incontinence symptoms. The other half (47%) were not bothered by urinary incontinence symptoms, but had concomitant symptoms including fecal incontinence, fecal soiling, prolapse requiring splinting, nocturia and urgency. (See table 3)


Table 1: Reasons for not seeking care (descending order of frequency) Thought these problems were normal part of getting older 51% The doctor never asked 17% Thought these symptoms were normal result of childbirth 12% Thought these problems were too embarrassing to mention 11% Not aware the problems could be treated or heard they couldn’t be 7% Apprehensive about treatment 7% Other 15% Multiple 49% Table 2: Characteristics of women socially bothered by incontinence Bothered Not Bothered p value Age 51 53 0.53 Post menopausal 63% 64% 0.94 Weight 164lb 150lb 0.04 Parity 2.8 2.7 0.62 Sought Care 44% 16% 0.001 Episodes of leakage Per week >3 <3 <0.001 Likert scale(0-3) >2 <2 <0.001 Urgency 50% 27% 0.01 Hysterectomy 37% 19% 0.03 Frustrated 67% 20% <0.001 UDI score 41 21 <0.001 IIQ score 18 4 <0.001 Table 3: Characteristics of women who successfully obtained care Obtained care Did not obtain care p value Raised issue with physician 76% 16% <0.001 Increased weekly number of Incontinence episodes 47% 13% <0.001 Increased urgency/nocturia 41% 27% 0.044 Prior surgery 9% 2% 0.007 Fecal incontinence 29% 15% <0.001 Doctor raised issue with them 37% 19% <0.001 Interpretation of results Women who are “socially bothered” by urinary incontinence, or have concomitant pelvic floor dysfunction, are more likely to seek and successfully obtain care. However, greater than 50% of women who are socially bothered by their incontinence do not seek care. It appears that up to one-half of women with moderate or severe incontinence that raise their concerns with a physician, may have their symptoms overlooked. Of women who successfully obtain care were more likely to have been asked by physicians about their symptoms. Concluding message Significant progress is needed to dispel common misconceptions in the general population in order to meet the healthcare needs of incontinent women. Women who have moderate to severe incontinence, based on self assessment, or concomitant symptoms are more likely to seek care. Unfortunately, not all of these women receive the care they seek. This information highlights the need for effective screening among primary care women’s health providers and treatment or referral to a specialist when concerns are raised by patients. Better access to urologic and urogynecologic care is essential. Reference 1. Factors associated with women’s decisions to seek treatment for urinary incontinence. Journal of Women’s Health 2003;12(7):687-98.


91 Taylor J1, Harrison S1, McGrother C2, Assassa P1

1. Pinderfields Hospital, 2. University of Leicester DIFFERENCES IN LOWER URINARY TRACT SYMPTOMS AND HELP SEEKING BEHAVIOUR BETWEEN ASIAN AND WHITE MEN. Hypothesis / aims of study The aim of the study was to establish whether there is any difference in lower urinary tract symptoms and related help seeking behaviour between the White and Asian ethnic groups in the UK. Study design, materials and methods This study was a secondary analysis of the MRC Incontinence Study, a cross-sectional, epidemiological survey of urinary symptoms based in Leicestershire, UK. A postal questionnaire was sent to adults aged over forty, selected at random from Health Authority registers. The questionnaire, which was designed and validated for this study, asked for details of demographics, general health, urinary symptoms and bother, and health service use. Ethnicity was recorded using the OPCS classification. For our analysis, symptoms occurring on a weekly basis were considered clinically significant, and were only recorded as present if they exceeded this threshold. Symptoms were regarded as ‘bothersome’ if they were described as causing ‘a lot’ of bother, or a ‘moderate’ to ‘severe’ problem. Prevalence rates were compared using the chi-square test. Logistic regression modelling was used to calculate odds ratios controlled for differences in age, socio-economic status and symptom severity where appropriate. Analysis was performed using SPSS for Windows v10.1. Results 7810 questionnaires were received, with 7401 respondents describing themselves as White, and 409 as Asian. Asian men had a mean age of 52.2 years, compared to 58.6 for White men. 31.1% of Asian men reported at least one LUTS, compared to 24.8% of White men (p=0.013). The age-adjusted odds ratio for Asian men having at least one LUTS is 1.86 times that of White men. Table 1 shows the prevalence rates by individual symptom. Table1: Prevalence rates of LUTS by ethnic group

Percentage prevalence Odds Ratios* Symptom

White Asian P value OR 95% CI Storage Frequency 5.3 12.2 0.000 3.03 2.15-4.29 Urgency 8.8 14.2 0.001 2.63 1.90-3.64 Nocturia 6.7 11.1 0.001 3.43 2.35-5.02 Urge Incontinence 3.8 7.6 0.000 3.45 2.22-5.35 Stress Incontinence 1.0 2.3 0.032 3.76 1.73-8.19 Voiding Slow Stream 11.3 11.4 0.950 1.41 1.00-2.01 Hesitancy 9.3 10.6 0.423 1.52 1.06-2.18 Intermittency 10.1 12.0 0.249 1.64 1.17-2.30 Straining 2.6 5.6 0.001 3.04 1.86-4.97 Post Micturition Incomplete void 8.2 10.3 0.161 1.75 1.22-2.51 Post micturition leak 11.4 13.8 0.179 1.48 1.08-2.04 *Asian compared to white. Adjusted for age and socio-economic status Overall, there were no differences in the prevalence of voiding or post micturition symptoms, except straining, but storage symptoms were much more prevalent in Asian men. However, using logistic regression modelling to control for the difference in age, Asian men appear to have a greater risk for all LUTS, except a slow stream. Odds ratios for voiding and post-micturition symptoms showed an increased risk of between 1.4 and 1.7 times that of white men. Straining was again the exception, with an odds ratio of 3.04 (95% CI 1.86-4.97). The increase in risk was much higher for storage symptoms, with odds ratios ranging between 2.6 and 3.7.


The overall proportion of men who found their symptoms bothersome was higher for Asian men (10.1% vs. 7.0%, p=0.015). However, when adjusted for the higher symptom levels in Asians, there was no difference in bother (OR 1.64, 95% CI 0.95-2.84). Although levels of felt need were also the same (OR 1.18, 95% CI 0.75-1.85), only 27.3% of Asian men who felt they needed help had sought help, compared to 53.1% of White men (p=0.001). Asian men were less likely to have consulted their GP about their symptoms (OR 0.55, 95% CI 0.37-0.83), but those that did were as likely to be referred to secondary care as White men (OR 0.56, 95% CI 0.25-1.27). Prostatectomy rates were the same in both groups (OR 0.76, 95% CI 0.43-1.71). Interpretation of results Despite their younger age, Asian men experienced significantly more urinary symptoms. When this age difference is controlled for, their increase in risk was almost 400% for some symptoms. There appears to be a clear separation between storage and voiding/post-voiding symptoms in terms of this risk increase, with rates of storage symptoms being much higher. It is unlikely that this can be accounted for by differences in reporting, as this may be expected to affect all responses equally. We feel, therefore, that this represents a true difference in symptoms experienced. For a given level of symptoms, Asian men report the same levels of bother and felt need as White men. However, fewer of these men actually seek help. This suggests that social influences have a greater effect on decisions to seek help in Asian men. Those that do seek help receive similar treatment to White men. Concluding message Asian men appear to be at greater risk of experiencing lower urinary tract symptoms, particularly storage symptoms. Despite similar levels of felt need and bother, they are less likely to seek help for their symptoms. Our results suggest a significant unmet need in the Asian community. We only report differences in symptoms experienced, and cannot make any comment on the pathophysiology which may underlie these differences. 92 Parsons M1, Williams M 1, Cardozo L 1, Bidmead J1, Hoey M 1, Thomas M 1, Robinson D 1, Balmforth J1, Dixon A1, Anders K 1 1. Kings College Hospital ANXIETY IN SPECIALIST CLINICS. Hypothesis / aims of study There are published data regarding women’s views on urodynamics, showing high levels of anxiety, and embarrassment (1,2). Colposcopy also been studied and shown to produce greater anxiety than major abdominal surgery (3). This is thought to reflect the possibility of a diagnosis of malignancy. We are undertaking a prospective study comparing state (procedure related) and trait (background) anxiety in women undergoing urodynamic investigations with women attending other specialist gynaecology outpatient departments. We present an analysis of data comparing urodynamics and colposcopy clinics. Study design, materials and methods The most commonly used psychometric method of assessing anxiety is the Spielberger State Trait Anxiety Inventory (STAI). We asked women aged 20-69, attending our one-stop urodynamics clinic and colposcopy outpatients for the first time, to complete the inventory immediately prior to the clinic appointment. The questionnaire takes approximately 10 minutes to complete and is appropriate for aged 11-12 years reading level. Recipients are asked to answer 20 questions each for state- and trait- anxiety against a four point Likert scale. Higher score equates with greater anxiety. Scores are then plotted against normative population data to control for age and sex, to calculate a percentile ranking of anxiety levels. We performed a paired samples t-test to compare the state and trait anxiety levels within each group and an ANOVA analysis to compare anxiety levels between the groups (SPSS, V11). Ethics approval was granted.


Results Demographic details. The age difference is controlled by the use of normative population data

UDS Colposcopy

n= 31 22 Mean age 45.2 years * 33.5 years * Range 25 - 68 years 23 – 49 years p= 0.0001

Summary of scores and ranking against normative data

Range Mean SD

State score (colposcopy) 21-71 47.18 12.35 State score (urodynamics) 24-75 48.35 13.3 Trait score (colposcopy) 23-65 43.38 11.77 Trait score (urodynamics) 20-61 43.25 11.21

Ranked state score (colposcopy) 3-100 76.63 25.03 Ranked state score (urodynamics)

16-100 79.54 24.35

Ranked trait score (colposcopy) 7-100 70.14 30.46 Ranked trait score (urodynamics)

0-100 74.16 31.86

Comparison Test Significance

State UDS vs trait UDS Paired t test 0.245

State colp vs trait colp Paired t test 0.490

State UDS vs state colp ANOVA 0.673

Trait UDS vs trait colp ANOVA 0.649

Interpretation of results There is no significant difference in state and trait anxiety within either group, and no significant difference in state scores and trait scores between the groups. The data confirm that the proneness to anxiety, and the actual anxiety levels prior to each clinic, are the same. Concluding message Attending specialist clinics imposes a significant psychological burden on women, but urodynamics not more than the others, and this should not be under-estimated. Measures to reduce anxiety need to be investigated and instituted. References 1. Women's attitudes to urodynamics: a questionnaire survey. BJOG 1999; Vol 106(8):851-6 2. Anxiety during urodynamics. International Urogynaecology Journal Oct 2003 - Proceedings of the 28th Annual Meeting of the International Urogynaecology Association, Buenos Aires, Argentina (Supplement); S10 3. Anxiety levels in women attending colposcopy clinics for treatment for cervical intraepithelial neoplasia: a randomised trial of written and video information. Br J Obstet Gynae 2001; 108:482-4


93 Morison M1, Staines H1, Gordon A1

1. University of Abertay Dundee A SYSTEMATIC REVIEW OF THE PREVALENCE OF NOCTURNAL ENURESIS IN CHILDREN AND YOUNG PEOPLE AGED 5 -18 YEARS AND ITS SOCIAL IMPACT ON THE INDIVIDUAL AND THE FAMILY Hypothesis / aims of study 1. To determine the prevalence of nocturnal enuresis in children and young people aged 5 – 18 years living

in Europe, the USA, Australia, New Zealand and Asia. 2. To evaluate factors affecting the age at which children become dry at night. 3. To gain more understanding of the social impact of nocturnal enuresis on the individual and their family. Study design, materials and methods A systematic search of the literature was undertaken. The following databases were searched: MEDLINE, CINAHL, EMBASE, BNI, INI, BIDS, ASSIA and the Cochrane Library for the years 1966 - 2003 using as key words: ‘nocturnal enuresis OR bed wetting AND epidemiology’. Over 1,500 relevant papers were identified from the UK, USA, Europe, Australia, New Zealand and Asia. References to other studies cited in the papers identified were followed up revealing some seminal works in this field dating back to the mid 1960s and even earlier. Where no definition of nocturnal enuresis was given or the definition was imprecise the study was excluded. Many studies failed to distinguish between primary and secondary nocturnal enuresis, or between nocturnal enuresis alone, diurnal enuresis alone and combined nocturnal and diurnal enuresis. Some important issues to consider when reviewing prevalence studies are described and the elements of good study design are highlighted. Results Bed wetting is a very common occurrence in younger children. The prevalence among five year olds is often quoted in the literature as 15-20% (1). However, not all five year olds are equally at risk. At this age the prevalence in boys is generally considerably higher than in girls, but this gender difference decreases significantly with increasing age. By the age of 7 years 5-10% of children are still wetting the bed frequently. The overall prevalence drops to 1-3% in the adult population but of these over 50% wet at least three times per week. These findings are congruent with a developmental typology of trajectories to night time bladder control (2). These authors have identified four broad categories: normal (84% of children); delayed acquisition, which may be transient (8.7%) or persistent (1.8%); chronic, affecting 2.6% of children up to the age of 15 years, and secondary onset or relapse, affecting 2.9% of children. There is good evidence that a family history of bed wetting is a risk factor. However, the influences of birth weight, birth order, the number of children living in the household, the family’s socio-economic status, and the education level of the parents are not clear cut and these factors have been found to be significant in some studies but not in others. Although for the most part a benign symptom of maturational delay, which will resolve spontaneously over time in most cases, the burden of nocturnal enuresis can be considerable, not only on the social and emotional well being of those who suffer with it (3) but also for their families. There is evidence that many parents in many countries do not seek professional help and attempt to manage the situation alone, within the home. Interpretation of results Critically reviewing the literature has revealed considerable variations in study design, including wide variations in the way that nocturnal enuresis is defined and wide variations in the methods of investigation, including variations in the study population, the means of sampling and enrolment, and the methods of data collection. These factors make interpretation and comparison of the results of individual studies difficult. The voluntary control of micturition is a social milestone as well as a developmental one. In different societies there are different expectations of the ages by which children should be dry, both by day and by night. However, nocturnal enuresis is a cause for concern among many parents living as far afield as Europe, North America, Australia and Asia, and the overall prevalence remains relatively constant, irrespective of the geographical location and the diversity of methods used to study it.


Concluding message Nocturnal enuresis is the most common chronic condition of childhood, after allergic disorders. There is evidence that its impact on families is underestimated by many professionals, yet there is now much help that can be offered including simple behavioural and pharmacological interventions and alarms. This is why it is so important to know how many children are affected, who they are and where they live, as this knowledge can have a considerable impact on service provision. In many societies there is evidence of considerable unmet need, especially in areas of high social and economic deprivation. Understanding and acknowledging the size of the problem is a useful first step towards doing something about it. References

1A guide to the treatment of enuresis for professionals (1995) (2nd ed) Enuresis Resource and Information Centre (ERIC), Bristol, UK. 2Developmental typology of trajectories to night-time bladder control: epidemiologic application of longitudinal latent class analysis (2003) Am J Epidemiol 157: 834-842. 3Bedwetting, behaviour and self-esteem: a review of the literature (2001) Child Care, Health and Development 27(2): 149-162. 94 Murphy M1, Culligan P1, Arce C1, Graham C1, Blackwell L1, Heit M1

1. University of Louisville CONSTRUCT VALIDITY OF THE INCONTINENCE SEVERITY INDEX Hypothesis / aims of study The Incontinence Severity Index (ISI) is a questionnaire composed of a two-items which assess the frequency (4 levels) and amount (3 levels) of urine leakage. The index value (1-12) is reached by multiplying the two items. The criterion validity of the ISI has been demonstrated by its high correlation with pad-weight tests [1]. We sought to test the construct validity of the ISI by assessing its correlation with a validated patient questionnaire designed to assess symptom severity, the short form of the Urogenital Distress Inventory (UDI-6). Study design, materials and methods A cohort of 170 women with a urodynamic diagnosis of stress incontinence who underwent corrective surgery completed the ISI and the UDI-6 both pre- and post-treatment. After entering the data in an SPSS database, we correlated the pre- and post-treatment responses between the ISI and the UDI-6 and its three subscales (Irritative, Obstructive, and Stress Symptoms). We also assessed the sensitivity of the ISI to change by correlating the percent change in score ([pre-treatment – post-treatment]/pre-treatment score) between the two instruments. Given the non-normal distribution of the data, the results were analyzed using a nonparametric test of correlation, the Spearman’s rho. Results The index values of the ISI correlated significantly with the pre-treatment (r=0.36, p<0.001) and post-treatment (r=0.78, p<0.001) UDI-6 scores. The percent change from pre- to post-treatment of the ISI was also strongly correlated with that of the UDI-6 (r=0.76, p<0.001). The ISI was highly correlated with two of the UDI subscales, the UDI-Irritative subscale (r=0.68, p<0.001) and the Stress subscale (r=0.84, p<0.001). The ISI was not significantly correlated with the pre-treatment UDI-Obstructive Symptoms subscale (r=0.14, p=0.22), and it was only moderately correlated with this subscale in post-treatment (r=0.25, p=0.003) scores. The ISI was strongly correlated with the other two UDI subscales, however, at almost every time interval. The correlations of the ISI with the UDI-Irritative Symptoms subscale at pre- (r=0.43, p<0.001) and post-treatment (r=0.73, p<0.001) were significant. The highest correlation in our study was seen between the ISI and UDI-Stress subscale in the post-treatment scores (r=0.84, p<0.001).


Interpretation of results The ISI was highly correlated with the UDI-6 at pre- and post-operative testing. The fact that the percent change in score was also strongly correlated between the ISI and the UDI suggests that the ISI is highly sensitive to the change in symptom severity seen after treatment. The strong correlation seen in with the Stress and Irritative Symptoms subscales provide evidence for the convergent validity of the ISI, while the weaker correlation seen with the Obstructive Symptoms subscale (more a measure of prolapse symptoms than incontinence) speaks to the divergent validity of the ISI. Concluding message The ISI is a simple, two-item questionnaire with high construct validity. The existing evidence of its correlation with pad-weight tests coupled with the strong correlation with measures of patient distress seen in this study strengthen the validity and potential value of the ISI as a clinical research tool. References [1] A severity index for epidemiological surveys of female urinary incontinence: comparison with 48-hour pad-weighing tests (2000) Neurourol Urodyn 19:137-45. 95 Coyne K1, Margolis M1, Zyczynski T2, Elinoff V3, Roberts R G4

1. MEDTAP International, Inc., 2. Pfizer, Inc, 3. Regional Clinical Research, Inc, 4. Dept of Family Medicaine, University of Wisconsin Medical School VALIDATION OF AN OAB SCREENER IN A PRIMARY CARE PATIENT POPULATION IN THE US Hypothesis/aims of study Overactive bladder (OAB), a symptom-based condition characterized by urinary urgency with or without urge incontinence and usually with increased urinary frequency and nocturia [1], has been estimated to affect 10% to 20% of the population [2,3]. According to 1 study, 73% of patients with OAB do not take any medication for the condition [2]. The goal of this study was to validate a screening tool to identify patients who are bothered by urinary symptoms consistent with OAB in a primary care setting. Study design, materials and methods he 8-item Symptom Bother scale of the OAB-q was evaluated as an OAB screener. Responses to the question, “How bothered are you…?” by particular symptoms were answered on a 6-point scale ranging from 0 (not at all) to 5 (a very great deal). Patients were recruited from 12 primary care practices and 1 general gynecology practice as they presented for regularly scheduled appointments. Pregnant patients or patients with a cognitive or other impairment that would interfere with completing a self-administered questionnaire were excluded. If the patient agreed to participate, they completed the screener, summed their responses, and provided the study staff with the completed screener. All screened patients were then asked 4 questions by the clinician regarding urinary symptoms (ie, frequency, urgency, nocturia, incontinence), 1 question regarding the reason for the office visit, and 3 demographic questions. If the patient had positive responses on any of the 4 urinary symptoms questions, additional questions regarding lifestyle and coping issues were asked. Upon completion of the clinician questions and based upon clinician opinion, the patient was diagnosed as “No OAB,” “Possible OAB,” or “Probable OAB.” All analyses were performed utilizing SAS (version 8.2). All statistical tests were 2-tailed and conducted with type I error probability fixed at 0.05. Descriptive statistics, chi-square tests, t-tests, and analysis of variance were used to evaluate the data. A series of multivariable logistic regressions were performed to assess the ability of the screener to identify patients diagnosed with OAB. Results 1299 patients were enrolled in this study; 1260 had complete data for analysis. Mean patient age was 52+17 years, 62% were women, and 89% were Caucasian. Patients experienced an average of 5.7+3.2 urinations per day and 1.3+1.2 urinations per night. Twenty-two percent of patients experienced urinary urgency; 18% experienced urge incontinence. The prevalence of Probable OAB was 12%, and Possible OAB was 20%.


There were significant differences (p < 0.0001) in the responses to the 6 coping behavior questions among patients diagnosed with Probable OAB, Possible OAB, or No OAB with the Probable OAB patients reporting the highest use of all coping behaviors. The most prevalent comorbid condition among male and female patients with OAB was an enlarged prostate (44%) and post-menopausal status (58%), respectively. The screener performed well with little missing data (0.2%–0.6%); high inter-item and item-to-total correlations (r = 0.42–0.86; p values < 0.001). The logistic regression models controlled for age and gender. The dependent variable was OAB diagnosis comparing No OAB versus Probable OAB. The c-index of this model was 0.96 with good model fit and a sensitivity and specificity of 98.0 and 82.7, respectively. For screener scores > 8 (range, 0–48), the odds ratio for having Probable OAB was 95.7 (95% CI: 29.3-312.0). Interpretation of results Simple screening methods can be used to screen for OAB in a primary care setting. An 8-item screener is highly successful in identifying patients with symptoms of probable OAB. Concluding message The OAB 8-item screener appears to perform well in identifying OAB patients in a primary care patient population. There appears to be a large unmet need among patients with bothersome OAB symptoms in primary care. Primary care physicians and patients would benefit from educational efforts to increase awareness of OAB symptoms and potential treatments. References 1. The standardisation of terminology of lower urinary tract function: report from the Standardisation Sub-committee of

the International Continence Society. Am J Obstet Gynecol 2002;187:116-126. 2. How widespread are the symptoms of an overactive bladder and how are they managed? A population-based

prevalence study. BJU Int 2001;87:760-766. 3. Prevalence and burden of overactive bladder in the United States. World J Urol 2003;20:327-336. FUNDING: Pfizer, Inc 96 van der Vaart H1, van Brummen P1, Heintz P1

1. University Medical Center THE CORRELATION BETWEEN THE UROGENITAL DISTRESS INVENTORY/INCONTINENCE IMPACT QUESTIONNAIRE AND OBJECTIVE MEASUREMENTS FROM THE BLADDER DIARY. Hypothesis / aims of study The Urogenital Distress Inventory (UDI) and the Incontinence Impact Questionnaire (IIQ) together form a disease-specific quality of life instrument that can be used in women with urogenital symptoms. The UDI measures if a symptom is present and the amount of bother the woman experiences from that symptom. Symptoms are grouped in domains. The Dutch version of the UDI consists of 5 domains, amongst them the UDI incontinence domain. The IIQ measures different aspects of quality of life and the Dutch version consists of physical functioning, social functioning, emotional functioning, mobility and embarrassment domains. The purpose of this study was to test the correlation between the UDI/IIQ subjective measures and data obtained from a 48 hour bladder diary. Study design, materials and methods In 2003 a total of 243 women visited our pelvic floor care unit for the evaluation of micturition problems. All women completed the UDI and IIQ questionnaire and a 48 hour bladder diary. On the diary they recorded the number of voids, volume of each micturition, number of incontinence episodes, numbers of pads used and the amount of urine loss (expressed as small = drops, medium = wet pad or underwear, or large = soaking). Spearman correlation coefficients were calculated using SSPS 10.0 software. Results The table shows the Spearman correlation coefficients and significance level.


Number of incontinence episodes per 24 hours

Number of pads used per 24 hours

Amount of urine lossed

UDI incontinence 0.439 * 0.370 * 0.488 * IIQ physical 0.052 0.011 0.068 IIQ social 0.156 * 0.097 0.074 IIQ emotional 0.071 0.044 0.015 IIQ mobility 0.166 * 0.093 0.159 * IIQ embarrassment 0.292 * 0.291 * 0.301 *

* p < 0.05 There is a statistical significant, moderate correlation between the objective parameters of severity of urinary incontinence from the bladder diary items and the subjective bother recorded on the UDI incontinence scale. On all the five IIQ domains the correlation with objective data is very weak or absent. The best correlation, although only small, is between the bladder diary items and the IIQ embarrassment domain. In addition, there is also a poor correlation between the UDI incontinence domain and the IIQ domains ( 0.13 IIQ social, 0.17 IIQ emotional, 0.19 IIQ physical, 0.26 IIQ mobility and 0.30 IIQ embarrassment). Interpretation of results The severity of urinary incontinence is often expressed in terms of number of incontinence episodes, numbers of pads used or in the amount of urine lossed. These data are also often used to report on the success of interventions. However, our data show that although there is a moderate correlation between incontinence episodes, number of pads used, amount of loss and the reported bothersomeness of incontinence, there does not seem to be a significant correlation with quality of life. Futhermore, the amount of bother reported does not correlate well with the impact that is reported on the different aspects of quality of life. The only weak correlation was found between the UDI incontinence domain and the IIQ embarrassment domain. Concluding message Both the objective indicators of the severity of urine incontinence as well as the reported bothersomeness correlate poorly with the subjective disease-specific quality of life. Apparently, there are more aspects on incontinence that determine quality of life besides the number of incontinence episodes and amount of urine loss. These data stress the importance to report on both objective as well as subjective parameters when describing the outcome of urinary incontinence treatment. Furthermore, one has to keep in mind that the IIQ was developed to account for the subjective severity of incontinence and a good correlation with objective parameters is not a necessity for its value. Improvement in quality of life is important from the patients point of view, and apparently this does not correlate well with a our objective measurements. 97 Goh J1, Krause H1, Sloane K1, Akhter S2

1. Royal Women's Hospital, 2. Dhaka Medical College Hospital MENTAL HEALTH SCREENING IN FISTULA WOMEN IN A DEVELOPING COUNTRY Hypothesis / aims of study Obstructed and prolonged labour is the most common cause of genital tract fistula world-wide. Luiz Mercado (1597) commented that the lives of women suffering from genitourinary and/or anorectal fistulas were “empty and tragic…. and how great are their embarrassments; for the bladder and the intestines move at the same time, and the uncontrolled urine and faeces run from the fistulae with ease……to render life very grim” (1). Most of the women with obstetric fistulas deliver stillborn babies, and many become social outcasts due to their condition. Although mental health consequences have been implicated in women with genital tract fistulas, there is a paucity of information in the published literature. A literature search (Medline) has failed to uncover any information on psychological health of women with genital tract fistula in the developing countries apart from the occasional case reports published in developed countries. The aim of this study is to screen women with genital tract fistulas for mental health dysfunction, prior to surgery.


Study design, materials and methods During a 3-month period, from December 2003 to March 2004, women presenting with a genital tract fistula to the Dhaka Medical College Fistula Unit, Bangladesh were invited to participate in the study. The women were screened using a shortened version of the General Health Questionnaire (GHQ-28). As many women were illiterate, the questionnaires were conducted by a medical officer (non-surgical) or nurse. The GHQ is a validated screening instrument that has been used in many countries including Cambodia, China and India. The questionnaires were completed prior to fistula surgery. The General Health Questionnaire is a screening instrument designed to detect current psychiatric conditions. The GHQ-28 contains questions covering 4 areas, namely social dysfunction, somatic symptoms, anxiety/insomnia and depression. In the guidelines for interpretation (2) of the GHQ-28, 5 or more positive answers (out of the 28 questions) are used to identify a probable case of mental dysfunction. Results Thirty-eight women completed the GHQ-28, and no woman declined to participate. The age of the women presenting with genital tract fistulas ranged from 18-42 years (median 26) and the time from antecedent event causing fistula formation to presentation at the hospital ranged from 3-180 months (median 6). Antecedent events included obstructed labour (37 women) and the remaining developed the fistula following a total abdominal hysterectomy. All women who had a prolonged obstructed labour delivered stillborn babies. Three women (8%) had a combined genitourinary and anorectal fistula while the remainder had genitourinary fistulas only. Each GHQ-28 took on average 10 minutes to complete. All women who were screened tested positive for probable mental dysfunction. Of the 28 questions, the range of positive answers was 11 to 28 (less than 5 considered normal). The domain pertaining to anxiety/insomnia had the highest number of positive scores. All women answered positive to ‘feeling nervous and uptight all the time’ and 37 of the 38 women denied ‘feeling well and in good health’ and again 37 women ‘felt that they were ill’ and ‘under constant strain’. The domain on depression had the least number of positive scores, in particular, the two questions on suicide scored the lowest in this domain. In this domain 35 of the 38 women have had thoughts of ‘worthlessness’, 20 women had thoughts of ‘killing’ themselves and 23 had the ‘idea of taking their own lives.’ Interpretation of results In this survey, all women with genital tract fistula screened positive for potential mental health dysfunction. The diagnosis for psychiatric conditions requires further verification. Most of the women in Bangladesh belonged to the Muslim religion. During the questionnaire, some had stated that it was against their religion to contemplate suicide or resort to suicide. It was therefore somewhat surprising that some women volunteered that they had contemplated taking their own lives. Concluding message This study demonstrated that women with genital tract fistula are at high risk of mental health dysfunction. Further research is required to assess the psychological impact of genital tract fistula together with formal psychiatric evaluation. If the high rates of positive screening are confirmed on psychiatric evaluation, then the management of women with genital tract fistulas must include psychological/psychiatric treatment. References 1. Vesicovaginal fistula – an historical survey. Obstet Gynecol 1954; 3: 337-341. 2. The detection of psychiatric illness by questionnaire. London: Oxford University Press, 1972. 98 Slieker-ten Hove M C P1, Vierhout M2, Bloembergen H3, Schoenmaker G4

1. Erasmus Medical Center, department of Gynecology, 2. University Medical Center Nijmegen, 3. Erasmus MC, Medical Faculty, 4. General Practitionergroup Brielle PREVALENCE OF BOWEL DISORDERS AND PELVIC ORGAN PROLAPSE COMPLAINTS IN RELATION TO URINARY INCONTINENCE IN A GENERAL FEMALE POPULATION. Hypothesis / aims of study The prevalence of double (urinary and faecal) incontinence is studied in different ways but is mostly focussed on groups of patients visiting urodynamic, urogynecological or colorectal clinics. The prevalence of these combined problems in the general female population however is hardly known.


This study was undertaken to evaluate the prevalence of faecal incontinence and constipation in relation to urinary incontinence in a population study of 1400 females, aged 45 – 85 years. Study design, materials and methods In a general population survey the entire female population aged 45-85 years n (2750) of a small town was invited to fill in a questionnaire with different validated questionnaires on urinary incontinence (UDI, IIQ), bowel disorders and prolapse related complaints. A total of 1398 women consented (50%). Mean age was 58 years. Bowel dysfunction was classified involuntary s loss of flatus, fluid, solid stool and constipation (defecation <3/wk). Results 1078 (77,1%) of this group of women suffered form either constipation, fecal incontinence, urinary incontinence, prolapse complaints or a combination of these. 807 women were urinary incontinent (59.5%) of which 29,5 % had stress incontinence, 5,9% urge incontinence and 22,4 % mixed incontinence. 720 women suffered from a form of fecal incontinence. 218 from fluid incontinence (12%) , solid stool incontinence (4%)) and 662 women had flatus incontinence (47%). 69 (4,9 %) women suffered from constipation (< 3/wk).

01020304050607080

perc

.

feca

lin

cont

inen

ce

urin

ary

inco

ntin

ence

prol

apse

com

plai

nts

1,2,

3 or

com

bine

d

1 2 3 4

prevalence of pelvic floor disfunction n=1398

Complaint Stress

Urge Mixed P Urge vs stress

Constipation 4.9 1.3 5.2 flatus inc 53.0 56.8 59.4 Ns Fluid stool 9.2 24.7 21.1 p = 0,000 solid stool 1.2 4.9 5.8 p = 0,022 Prolapse complaints (159)

9.7 20.7 13.7 p = 0,004

We specifically studied the relationship between the specific form of urinary incontinence and other pelvic floor symptoms (Table) Urge incontinence was significantly more prevalent in women with complaints of POP as well in women with incontinence of solid and fluid stools. Interpretation of results Pelvic floor problems either alone or in combination are extremely prevalent in our study group with 77 % (1078) of the women suffering from at least one of the major symptoms. 36 % (388) of them had only one problem and nobody reported on all the investigated symptoms. 64 % (690) two or more complaints. It is therefore clear that these symptoms should not be studied alone but in relation to each other. We found a high significance between the presence of urge incontinence and POP This is compatible with other studies who found symptoms of overactive bladder in POP possible related to mild obstruction cause by a kinking effect of the vaginal prolapse on the urethra.The relationship between urge incontinence and faecal incontinence is puzzling. These results were compared with results from an earlier study(1). There was no relation found in the flatus incontinence group what could explain a possible internal sphincter weakness as suggested in a comment on the earlier mentioned study (2). However, urge patients


are complaining more and have a lower quality of life score than the stress incontinent group and could partly be the reason of these scores. Possibly there are other confounding factors explanatory for this relation. Concluding message When studying prevalence of pelvic floor problems it is mandatory that these problems are not studies isolated but combined and in relation to each other. Isolated studies of only one aspect will certainly underestimate the magnitude of these problem. Since pelvic floor problems are so frequently occurring as combination of symptoms the patients presenting with one of these problems should always carefully be investigated for all of the other aspects. This requires a well organised multidisciplinnary setting. References

1. Prevalence of faecal incontinence among women with urinary incontinence, Brit J Obstet Gynaecol, , 1998; 105, 1211-1213.

2. Comment on article Prevalence of faecal incontinence among women with urinary incontinence, Brit J Obstet and Gynecol, 1999, 106 (11), 1233-4.

3. Bowel disorders and their botherscore, Abstract IUGA 2003. FUNDING: unrestricted grant from NV Organon Netherlands 99 De Gennaro M1, Di Ciommo V2, Capitanucci M L3, Mosiello G1, Orazi C 4, Schingo P5, Adorisio O6, Tubaro A7

1. Bambino Gesu' Children's Hospital, Dept Nephro-Urology, Urodynamic Unit , 2. Bambino Gesu' Children Hospital, Epidemiology and Statistics Unit, 3. Bambino Gesu' Children's Hospital, Dept Nephro-Urology, 4. Bambino Gesu' Children's Hospital, Dept Radiology, 5. Bambino Gesu' Children's Hospital, Dept of Radiology, 6. Mayer Children's Hospital, Pediatric Surgery Unit, 7. Urology Dept "La Sapienza" University of Rome ACCURACY OF BLADDER VOLUME DETERMINATION BY BLADDERSCAN IN PEDIATRIC AGE Hypothesis/ Aim of the study Ultrasound imaging has been used and widely accepted as an alternative to catheterisation to evaluate bladder volume in children with voiding dysfunction. Recently, a small portable automated unit, the BladderScan, has been introduced to measure bladder volume . BladderScan is simple to use and non-invasive instrument which provides a direct evaluation of bladder volume expressed in ml; it can be used by physicians, nurses and patients themselves. Nevertheless, there are conflicting evidences regarding the accuracy of BladderScan in determining bladder volume . Particularly, in children a low systematic versus an high mean absolute error has been found comparing BladderScan and Utrasound measurement of bladder volume(1).In order to asses the accuracy of BladderScan in children, we compared and analysed the results of bladder volume evaluation performed with ultrasound imaging and BladderScan. Study design, materials and methods Bladder volume was measured using both ultrasound and BladderScan, during the same session, in 92 (42 females and 51 males) children (average age: 4.6 ± 3.9 years; range: 4 months – 16 years). Children underwent ultrasound for different pathologies: hip dysplasia n=23, recurrent urinary tract infections n=25, hydronephrosis =38, recurrent abdominal pain n=6 . BladderScan evaluation was carried out by the same operator, using a standard instrumet for adults; ultrasound was performed by two operators using the same formula to measure bladder volume in ml [(anterior-posterior x superior-inferior x transverse dimension) / 2]. Evaluations were made with patients in supine position and not changing position between measurements. Patients were classified into subgroups according with age: 0.3 to 2 (n= 34, average age: 0.9 ± 2) years, 3 to 6 (n= 37, average age: 4.3 ± 1.2) years, 7 to 14 (n=21, average age: 9.5 ± 2) years. Moreover, in children > 2 years, bladder volume was grouped as follows: < 20%(n=31), 20-50% (n=18), >50% (n=25) of the expected bladder capacity (BC) for age [(30 x age in years) + 30]. The data recorded with ultrasound and BladderScan in age and bladder volume subgroups were compared by calculating the Pearson’s correlation index (IR) and statistically analysed (Fischer’s z).


Results An overall correlation index of 0.98 (p< 0.0001) was found between ultrasound and BladderScan. The results of comparison between ultrasound and BladderScan among the subgroups by age and the sunbgroups by bladder volume in respect to BC are shown in figure 1 and 2. The data obtained matching age and bladder volume subgroups are reported in table 1. Table 1: Subgroups by age matched with subgroups of bladder volume defined in respect to expected bladder capacity for age.

Expected Bladder Capacity for Age Age Subgroups <20% >20% 3 – 6 years IR=0.73

(n=16) IR=0.63 (n=15)

7 – 16 years IR=0.69 (n=7)

IR=0.98 (n=26)

BLADDER VOLUME - Fig. 1

0

50

100

150

200

250

300

0 50 100 150 200 250 300

Ultrasound (ml)

Bla

dder

Sca

n (m

l)

3m - 2 yrs 3 - 6 yrs 7 - 16 yrs

BLADDER VOLUME - Fig. 2

0

50

100

150

200

250

300

0 50 100 150 200 250 300

Ultrasound (ml)

Bla

dder

Sca

n (m

l)

<20% BC >20-50% BC >50% BC

Interpretation of results We found a statistically significant (p< 0.0001) correlation index (IR) among the age (0.3 –2 years: IR= 0.73; 3 - 6 years: IR= 0.92; 7-16 yaers: IR= 0.97) and the bladder volume(<20%: IR= 0.75; 20-50%: IR= 0.96; > 50%: IR= 0.92) subgroups. Nevertheless, analysing data, we found a lower Pearson’s correlation index between the two methods in children younger than 3 years (IR=0.73) and if bladder is filled below 20% (IR= 0.75) of BC. Matching subgroups by age with those of bladder volume, the correlation index resulted significant (p< 0.000001) in children aged 7-16 years and with bladder volume greater than 20% of BC (IR=0.98), only. Concluding message BladderScan seems to be applicable with good accuracy in evaluating children older than 6 years and with bladder greater than 20% of the expected bladder capacity for age. The data collected in infants and in children with low bladder volume indicates the need of a more accurate pediatric Bladderscan. References 1) Clinical agreement between automated and calculated ultrasound measurements of bladder volume. The British Journal of Radiology, 76: 832-834, 2003


100 Macaulay M1, Pettersson L1, Fader M1, Brooks R1, Cottenden A1

1. University College London A RANDOMISED CROSSOVER STUDY OF DISPOSABLE PADS FOR INCONTINENT CHILDREN Hypothesis / aims of study Children with delayed acquisition of continence require an absorbent product, which has traditionally meant diapers (Figure 1a). Pull-up style pads (pull-ups) (Figure 1b), a more recent innovation, may have advantages and are increasingly demanded by parents. However, pull-ups cost around 50% more than diapers and no study has compared their performance with diapers. Figure 1a: Diaper Figure 1b: Pull-up

This study aimed to:

• Evaluate all disposable pull-ups for children available in the UK in 2002 (n=5) • Compare this design group as a whole with a representative sample of five disposable diapers • Establish parent / child preference for these design groups

Study design, materials and methods Design: a randomised crossover trial – every subject tested all products. Subjects: 61 children with learning / physical disability (age range: 3-15 years) were recruited who had been assessed as requiring a pad for heavy daily incontinence supplied by the UK health service and had parents/guardians (carers) willing to assist. Exclusion criteria were acute or terminal illness, or an inability to wear either one of the designs. Products: The products, selected in consultation with manufacturers and the UK national health purchasing agency, were grouped as follows: Group 1 – Pull-up design (all five disposable pull-ups available in the UK) Group 2 – Diaper design (a representative sample of five disposable diapers) Group 1: Pull-ups Group 2: Pull-ups Manufacturer Product Manufacturer Product First Quality International Prevail All Nites Abena UK Ltd. Bambolina Paul Hartmann Ltd. Fixies Unisex Paul Hartmann Ltd. Fixies Ultra Dry Kimberly-Clarke Huggies Drinite Ontex UK Ltd. Moltex Elastic Extra

Dry Procter & Gamble Pampers Easy Up Procter & Gamble Pampers Baby-Dry SCA Hygiene Libero Up & Go

SCA Hygiene Libero Methods: Group order was randomised and individual products were randomised within their group. Each product was tested for up to one week. Aspects of product performance which subjects/carers had indicated to be important e.g. leakage/absorbency, fit and comfort were rated in a validated product performance questionnaire using a 3-point rating scale of ‘good’, ‘okay’ or ‘poor’. Wet product weights and amount of


leakage were recorded in a pad leakage diary on a 3-point scale of ‘a lot’, ‘a little’ or ‘none’. At completion of testing, qualitative data were collected by asking carers to state and comment on their design preference for both day and night use. Results

• A significant difference (p<0.005) was found for parent preference for diapers for night use (65% preferred diapers; 27% preferred pull-ups)

• No significant differences were found for design preference for day use (57% preferred diapers; 38% preferred pull-ups)

• Almost all parents did state a clear preference for one or other design (95% for day use; 92% for night use) and qualitative data showed that their decisions were based on the individual needs of their children

• The pad diaries showed that leakage performance was similar for the two designs although the diapers were perceived to be more absorbent than the pull-ups. This was substantiated by measurement of Rothwell capacity1 of both diapers and pull-ups which established the mean capacity of the diapers as 181g greater than the pull-ups

• There were significant differences between the performance of the individual pull-ups: for the primary outcome indicator ‘overall opinion’, Pampers Easy Up Pants performed significantly better than two other products in the group (p<0.005)

Interpretation of results - Each design has a place in the containment of leakage for this group of children and the appropriateness of either for day time use is dependent on a range of factors - Pull-ups are more suitable for children who:

• are able to assist with pad changing • are developing independence in toileting e.g. starting to remove and replace underwear themselves • do not wear callipers or adapted footwear • are not faecally incontinent • require a more discrete product for day use

- Diapers are more suitable for children who: • cannot assist with pad changing • use callipers, adapted footwear and or wear trousers and require a discreet pad change • require a more absorbent product where discreteness is less of an issue e.g. night use • have faecal incontinence

- Although most pull-ups and diapers performed similarly to the other products within their design group, significant differences did exist, either as a result of problems achieving a good fit or indirectly related to fit e.g. the product was too small or too large and leaked more than the other products. - The parents made design preference choices based on practical issues and the specific needs of their children rather than the desire to have a novel or more aesthetically acceptable product. Concluding message Our findings indicate that both pull-ups and diapers have a place in the management of incontinence for disabled children. Diapers are preferable for night use and for most children during the day but the additional cost of pull-ups for day use can be justified for selected children by a thorough assessment of the child and family circumstances and both designs should be made available to these children. References 1 International Standards Organisation (1996) 'Urine absorbing aids Part 1: Whole product testing'; ISO 11948-1; 1996.


101 Kracochansky M1, Koch V1, Schneider E 1, Arap S1, Trigo Rocha F1

1. University of Sao Paulo TREATMENT OF VESICAL SPHINCTER DYSSYNERGIA IN CHILDREN USING EMG-BIOFEEDBACK – RESULTS OF A 2 YEAR FOLLOW-UP STUDY Hypothesis / aims of study Non-neurogenic lower urinal tract dysfunctions (NNLUTDs) in childhood usually manifest themselves by urinal infections in conjunction with urinal incontinence. It is believed that some of the methods children use to achieve bladder control are the source of many problems. Some children learn to retain urination by contracting the sphincter, rather than relaxing it while contracting the detrusor, causing an increase of vesical pressure and incomplete evacuation of the bladder and leading to a functional obstruction of bladder evacuation [1]. EMG-Biofeedback uses equipment that monitors muscular activity (pelvic and abdominal) and shows these data to the patient instantaneously and continuously, in the form of visual and/or auditive signals. The child learns to contract and relax the musculature of the pelvic floor and uses this knowledge during urination [2]. Study design, materials and methods We conducted a prospective, nonrandomized clinical study involving uncoordinated miction patients, which received the approval of the Hospital Ethics Committee. Twenty one children with uncoordinated miction (5 boys and 16 girls; mean age, 10 years) were selected as candidates to physiotherapeutic treatment and training with biofeedback in an outpatient clinic of Children Mictional Dysfunction. During the sessions, pelvic floor training and biofeedback were reinforced. At the end of each session a flowmetric study was made. The evaluation of the results was made through urine examinations for control of infections of the urinary tract (IUT), by analyzing the number of pads used in a month (PD), by filling out a bladder diary, the number of incontinence episodes in a month (IE), a vesical ultrasonography exam for evaluation of pos-mictional residue, a cistography for evaluating vesical-uretral reflux (RFL), an urodynamic study, and by filling out the Quality of Life Questionnaire (QL). All of these measurements were taken pre and post treatment. The following aspects were evaluated in the QL questionnaire: self esteem, social relations, school performance and home behavior.The statistical significance levels was of 0.05 levels. Results The mean follow up period was 24 months. Bellow is a table showing the main results of our research. In the medical examinations (IE, IUT, PD, RFL) as well as in the clinical evaluation (QL), our statistics indicated significant improvement in the post treatment phase compared to the pre treatment period. IE IUT PD RFL QL Pre Treatment 33.8 6.3 31 0.76 1.5 Post Treatment 0.5 0.2 0 0.19 4.7 p value 0.0001 0.0001 0.0001 0.0001 0.0001 IE: mean of the number of incontinence episodes in a month; IUT: mean of infections of the urinary tract a month; PD: mean of number of pads used in a month; RFL: mean of vesical-uretral reflux; QL: mean of Quality of Life score. Interpretation of results Our results indicate that the rehabilitation of the pelvic floor in children with NNLUTDs presents to be a safe, non invasive therapeutic resource and associated to significant and lasting results. Concluding Message This combined therapy may represent the first choice for the treatment of children with non-neurogenic lower urinal tract dysfunctions. Our results sugest that combining pelvic floor physiotherapy with EMG-Biofeedback is a non-invasive and secure method with enduring results. References 1. Standardization and definitions in lower urinary tract dysfunction in children. BJU 1998, 81, Suppl. , 1-16. 2. Pelvic –floor therapy and toilet training in young children with dysfunctional voiding and obstipation. BJU Int., 2000, 85(7):889-93.


102 Kajiwara M1, Inoue K2, Kato M1, Kurihara M1, Usui A3, Usui T1

1. Hiroshima University, 2. Miyazaki University, 3. Hiroshima Prefecture Rehabilitation center VIDEOURODYNAMIC ASSESSMENT FOR DAYTIME URINARY INCONTINENCE ATTRIBUTABLE TO OVERACTIVE BLADDER IN CHILDREN Aims of study Overactive bladder symptoms (OAB) including urgency, increased daytime frequency anddaytime urinary incontinence (DUI) are considered among the most common and bothersome developmental disorders of childhood. DUI is perhaps the most troublesome of these, and its prevalence in schoolchildren is reported to be 6.3% (1). Some cases carry a risk of urinary tract infection (UTI), vesicoureteral reflux (VUR) and constipation, and sometimes persist into adolescence. It is generally thought that OAB symptoms decrease spontaneously with age. However, the prevalence and conditions of children with OAB symptoms have been obscure. The aims of this study were to examine the associated symptoms of children with DUI attributable to OAB and to clarify their conditions. Materials and methods Among children who had been hospitalized at our department with a chief complaint of OAB symptoms during 1998 to 2003, 106 children were retrospectively enrolled into the study. The inclusion criteria for the children were that they were over six years old, without neurological abnormalities, and had not responded to first-line treatment. First-line treatment consisted of ensuring that the children understood the normal vesicoureteral anatomy and mechanism of micturition, and behavioral modification employing a bladder diary, timed voiding therapy, correction of voiding posture and treatment of constipation with/without anticholinergic drugs (oxybutynin chloride) for more than three months. Children who had monosymptomatic nocturnal enuresis only and/or who had pure stress incontinence were excluded. To investigate the urological conditions in these children, all of them underwent voiding cystourethrography and a pressure flow study (videourodynamic study; VUDS). On the basis of their VUDS data, the children were classified into the following six groups according to the standardization and definitions of lower urinary tract dysfunction in children stipulated by the International Children’s Continence Society (2): urge syndrome (US), dysfunctional voiding (DV), lazy bladder (LB), and normal (Norm), unknown, or congenital organic lower urinary tract obstruction (BOO). To examine the conditions and the associated symptoms of children with DUI attributable to OAB, we compared the VUDS findings among the six groups. The data were analysed statistically using non-parametric tests (Mann-Whitney U test and the chi-squared test). Results The patients comprised 61 boys and 45 girls aged between 6 and 15 years (mean age 8.3±2.2 years). There was no significant age difference between the sexes. As OAB symptoms, all children had DUI occurring more than weekly, which was the most frequent symptom, and 67 of them (67.9%) had nighttime bedwetting (occurring every night in 50 children (47%), twice to five times weekly in 15 (14%), and once a week in two (1.9%)). A history of pyelonephritis was found in 12 children (11%; 2 boys and 10 girls), and cystitis in 13 (12%; 4 boys and 9 girls). Constipation was detected in 31 children (29%; 7 boys and 24 girls) with a significant difference between the sexes, including 4 children with faecal incontinence (Table 1). VUR was newly detected in 32 children (30%; 34 ureters, 2 bilateral cases), and 74% of them were of slight severity. With regard to the VUDS findings, the mean functional bladder capacity of children with US, LB and BOO was significantly lower than that expected for age (p<0.05). Involuntary detrusor contraction was detected in 63 children (59%). In children with Norm and LB, the capacity was almost equal to that expected for age. However, children with LB had a significantly large post-void residual (p<0.05; mean 81 ml). Mean maximum flow rate (Qmax) in LB children was significantly lower than that in Norm children, and there was no difference in mean Qmax between BOO, US and DV. Mean detrusor pressure at maximum flow in US, DV and BOO children was significantly higher than that in Norm children (p<0.05; Table 2). Concluding message Our VUDS findings demonstrated that children with OAB who had not responded to first-line therapy had a wide range of pathological conditions, including a small-capacity bladder, IDC, low-grade VUR and a large post-void residual. Nighttime bedwetting, a history of UTI and constipation were significantly associated symptoms. VUDS is a relatively invasive and upsetting examination for children (3). However, more attention


should be paid to the possible link between DUI, UTI, low-grade VUR and constipation when they accompany OAB, and VUDS should be applicable and available. Table 1 Conditions of each group at the time of videourodynamic study Groups Norm US DV LV BOO Unknown Total No. of pt 15 44 12 3 31 1 106 Bedwetting n (%)

8 (53.3)

30 (68.2)

8 (66.7)

3 (100)

18 (58.0)

0 (0)

67 (63.2)

History of UTIs n (%)

2 (13.3)

13 (29.5)

2 (16.7)

1 (33.3)

7 (22.6)

0 (0)

25 (23.6)

Constipation n (%)

5 (33.3)

14 (31.8)

5 (41.7)

2 (66.7)

5 (16.1)

0 (0)

31 (29.5)

Table 2 The videourodynamic findings of each group Norm US DV LV BOO unknown VV

245±84 164±90 130±69 223±173 (PVR =80)

162±77 636

IDC (n) (%)

0 (0)

30 (68.2)

9 (75.0)

2 (66.7)

22 (71.0)

0 (0)

P-Qmax 50±11 69±43 68±25 77±11 71±24 unknown Qmax 23±13 16±8.9 13±7.6 5.8±3.7 13±5.6 18

VV= voided volume (ml); IDC =involuntary detrusor contraction; P-Qmax= detrusor pressure at maximum flow rate (cmH2O); Qmax= maximum flow rate (ml/s); PVR= post void residual (ml). References 1. Kajiwara M, Inoue K, Kurihara M, et al. The micturition habits and prevalence of daytime urinary incontinence in

Japanese primary schoolchildren. J Urol 2004 171(1): 403-407 2. Norgaard JP, van Gool JD, Hjalmas K, et al. Standardization and definitions in lower urinary tract dysfunction in children.

International Children's Continence Society. Br J Urol 1998; 81 Suppl 3:1-16 3. P. Abrams. Editional comment. Br J Urol 1995; 76: 781-782 103 Kim K M1, Lee S W1

1. Seoul National University NERVE SPARING BILATERAL EXTRAVESICAL DETRUSORRHAPHY Hypothesis / aims of study The modified Lich-Gregoir extravesical reimplantation is an effective method for correcting vesicoureteral reflux and has advantages compared to intravesical approaches, including decreased postoperative discomfort, decreased bladder spasm, decreased hematuria, and a shorter hospital stay. However, there is reluctance to perform bilateral detrusorrhaphy because of the reported high incidence of voiding dysfunction postoperatively. We evaluated the outcome and incidence of urinary retention after bilateral detrusorrhaphy using modification for avoiding disruption of detrusor innervation. Study design, materials and methods We reviewed the charts of 22 consecutive patients (12 boys and 10 girls) who underwent bilateral extravesical reimplantation between October 2002 and February 2004. The patients were divided into two groups according to the type of paraureteral myotomy. In the late period of our experience, since June 2003, we have performed distal myotomy which is curved ventromedially just below the UVJ for saving trigonal innervation rather than extended linearly. Group 1 consisted of 12 patients (M:F 5:7, mean age 4.5 yrs, range 5 months to 7 years) who underwent bilateral detrusorrhaphy using conventional linear myotomy along the ureteral course. Group 2 (M:F 7:3, mean age 3.1 yrs, range 8 months to 7 years) consisted of 10 patients who underwent bilateral detrusorrhaphy using previously mentioned nerve sparing myotomy (‘J’ shaped incision).


Postoperative voiding was monitored by uroflowmetry and by postvoid residual urine volume with ultrasound bladder scan or catheterization. Urinary retention was defined as the emptying failure requiring temporary urethral diversion or intermittent catheterization. Postoperative follow up included VCU and renal USG 3 to 4 months postoperatively. Further USG or DMSA scan was performed in selected cases. We compared the rate of postoperative urinary retention as well as successful reflux resolution between both groups. Results The mean duration of follow up in group 1 (12 patients) was 11 months (range 1 to 17) and the grade of reflux was I in 1 ureter, II in 9, III in 7, IV in 5, V in 2. In group 2 (10 patients), the mean duration of follow up was 5.4 months (range 1 to 9). The reflux grade was I in 2 ureters, II in 2, III in 5, IV in 9, V in 2. Preoperatively mean maximal flow rate was 16.7 ml/sec in group 1 and 15.9 ml/sec in group 2 each other (p>0.05). At uroflowmetry, mean voided volume was 127.8 ml in group 1 and 98.1 ml in group 2. Nobody of 22 patients had the residual urine volume larger than 25% of total volume on preoperative RU check. The overall success rate for reflux resolution was high. However, 2 patients (3 ureters) in group 1 did not acquire the resolution of reflux at 3 or 4 months follow up. The success rate was 85 % in this group. On the other hand, all (7 patients) that underwent initial follow up VCU in group 2 had resolution of reflux. Mean postoperative date of catheter removal and voiding trial was 6.3 day (range 4-15) in group 1 and 4.0 day (range 3-7) in group 2. Urinary retention developed in 3 (25%) of group 1, but in none (0%) of group 2 (p<0.05). All that experienced urinary retention required Foley catheter re-indwelling, but the resolution of voiding difficulty appeared at 8 days, 9 days, and 26 days postoperatively in each other. During the further follow-up periods, no serious voiding dysfunctions were found in both groups. Interpretation of results It seems that bilateral extravesical detrusorrhaphy using modified myotomy curved ventromedially below the UVJ decreased the rate of postoperative urinary retention and persistent reflux because the incision parallel to the traverse nerves below the UVJ area could minimize nerve damage and achieve enough tunnel length as possible. Concluding message Compared to conventional bilateral extravesical detrusorrhaphy, nerve sparing bilateral detrusorrhaphy using ‘J’ shaped modified myotomy showed decreased incidence of urinary retention postoperatively. It seems to be efficacious procedure associated with low morbidity for correcting bilateral vesicoureteral reflux in children. References J Urol 2001;165:1652-5 J Urol 1999;162:1197-1200 J Urol 1998;160:1004-6 104 Tanaka H 1, Kakizaki H1, Moriya K1, Furuno T1, Nonomura K1

1. Department of Urology, Hokkaidou University Graduate School of Medicine IS NECESSARY ANTI-REFLUX SURGERY AT THE TIME OF AUGMENTATION CYSTOPLASTY FOR CHILDREN WITH NEUROGENIC BLADDER AND HIGH GRADE VESICOURETERAL REFLUX? Hypothesis / aims of study Vesicoureteral reflux (VUR) in patients with neurogenic bladder is often eliminated by correction of abnormal bladder dynamics by conservative management including intermittent catheterization and anticholinergics. However, VUR that is refractory to conservative treatment does exist in some patients and is the cause of progressive upper tract deterioration. Augmentation cystoplasty is the last resort for these problems. Whether augmentation cystoplasty alone or in combined with antireflux surgery should be performed is quite controversial. We analyzed our experience of augmentation cystoplasty without antireflux surgery in patients with neurogenic bladder and high grade VUR.


Study design, materials and methods Since August 1998, 2 males and 3 females with poorly compliant bladder and high grade VUR (grade III or more according to international classification) have undergone augmentation ileocystoplasty without anti-reflux surgery. Underlying disease was myelomeningocele in all patients. Maximum conservative treatment failed in all patients, and a temporary cutaneous vesicostomy was performed in 1 patient at age of 6 months. Hydronephrosis was observed in 5 kidneys of 4 patients preoperatively. VUR was bilateral in 3 patients and unilateral in 2, and their grades were II in 1 ureter, III in 5 ureters and IV in 2 ureters. Intravesical pressure at VUR occurrence ranged from 2 to 36 cmH2O (mean 11.8). Mean age at operation was 11.9 years (range 3 to 19), and postoperative follow-up periods ranged from 2 to 52 months (mean 23 months). Results All patients underwent videourodynamic study postoperatively. Mean bladder capacity and bladder compliance increased from 220 ml (range 90 to 350) and 5.1 ml/cmH2O (range 2.5 to 8.5) preoperatively to 412 ml (range 250 to 500) and 29 ml/cmH2O (range 25 to 31) postoperatively, respectively. VUR disappeared in 7 ureters (grade IV in 1 ureter, grade III in 5 ureters and grade II in 1 ureter) and improved in 1 ureter (from grade IV to grade II) within 2 years postoperatively. Hydronephrosis in 5 kidneys was all resolved postoperatively. Febrile urinary tract infection occurred in only one patient with down-grading but persisting VUR, in whom reeducation with intermittent catheterization regimen was successfully introduced to prevent recurrent urinary tract infection. Interpretation of results Surgical correction of abnormal bladder dynamics resolved or improved VUR and hydronephrosis in patients with neurogenic bladder and VUR. Concluding message Results in this study indicate that anti-reflux surgery is not required at the time of augmentation cystoplasty for patients with end-stage neurogenic bladder and high grade VUR. 105 Marschall-Kehrel A1, Mürtz G 2, Kramer G3, Jünemann K P4, Hjalmas K5

1. Urology Consultancy, Berursel, 2. APOGEPHA Arzneimittel GmbH, Dresden Germany, 3. Bennebroek, the Netherlands, 4. Department of Urology and Paediatric Urology, University of Kiel Germany, 5. Paediatric Urology Göteborg University, Sweden LONG-TERM RESULTS AND RELAPSE RATES IN CHILDREN SUFFERING FROM MONOSYMPTOMATIC NOCTURNAL ENURESIS AND OVERACTIVE BLADDER Hypothesis / aims of study Management of children with primary nocturnal enuresis (PNE) or OAB is usually evaluated only regarding short-term clinical outcome. There are only a few studies reporting on long-term outcome and relapse rates. The aim of our study was to determine long-term outcome and relapse rates under special consideration of the recently proposed algorithms for both clinical diagnoses (1,2). Study design, materials and methods All children were assessed clinically according to the criteria of the ICI (3) by history, bladder diaries over a period of two weeks, urinalysis, ultrasound and at least two EMG-uroflows. Nocturnal diuretic volume was calculated by diaper weight plus the first morning micturition. Dysfunctional voiders were excluded. Urotherapy was applied in all patients for two weeks encompassing timed drinking and modification of micturition habits. Non-responders to urotherapy with nocturnal enuresis were then assigned to desmopressin monotherapy applying a structured withdrawal program. After this first treatment period, partial responders entered an individualized treatment (anticholinergics, biofeedback, alpha-blocker, enuresis alarm or psychotherapy), combined with desmopressin (1). Outcome was evaluated as relief of bedwetting. In cases of urinary incontinence another treatment algorithm (2) was used. It consisted of a four week first treatment period with propiverine hydrochloride (0.4 mg bid/kg b.w.) monotherapy with gradual reduction of dose, which was combined in partial responders during the second treatment period with individualized


adjuvant therapy (alpha-blocker, desmopressin, or biofeedback). Outcome was evaluated as achievement of continence. Non-responders of both clinical entities were referred to specialized management. Results The enrolled 259 PNE children comprised 92 girls and 167 boys, age range 5 – 18 years (arithmetic mean 8.11 years). The long-term results after termination of treatment refer to a minimum follow-up of 3 months up to 79 months (arithmetic mean 35.13 months). In these long-term results 18 patients were lost to follow-up. Nocturia occurred in 12% of the 241 patients (3% urotherapy, 6% desmopressin, 3% partial responders) after termination of treatment. Thirteen children relapsed (1/42 urotherapy, 4/136 desmopressin, 6/61 combination treatment, 2/17 partial responders without continued treatment). Thus, the overall relapse rate was 5.4% (2.4% urotherapy, 2.9% desmopressin, 9.8% combination treatment, and 11.8% partial responders who did not receive combination treatment). The enrolled 96 OAB children comprised 36 girls and 60 boys, age range 5 – 14 years (arithmetic mean 6.9 years). The long-term results after termination of treatment are based on a minimum follow-up of 3 months up to 86.months (arithmetic mean 24.7 months). 9 patients were lost to follow-up. 18 children relapsed during the period with dose reduction. Therefore this subgroup required extended treatment periods of up to 26 months, during which all OAB symptoms resolved. In 2 cases incontinence improved, therefore treatment was terminated. In OAB children no relapse occurred. Another 5 patients are still under treatment. Interpretation of results Decreased self-esteem in children suffering from PNE has been reported. However, our data reflect that OAB children might be even more affected regarding self-esteem and perceived quality of life. The low relapse rate documented in our study is promising and should probably be attributed to the structured withdrawal program. Individualized adjuvant treatments in partial responders improve success rates further and should therefore be incorporated into daily practice. In nocturia two subgroups could be discerned: nocturia as relapse (n=28) and as maturation (n=3) in partial responders. In children with OAB, no relapses were recorded in contrast to the situation in PNE. Twenty-six percent of the children with OAB required an extended treatment period for achieving continence, and in 5 children antimuscarinic treatment is still ongoing. Concluding message The long-term treatment outcome in PNE and OAB children, based on the proposed treatment algorithms, is promising. A structured withdrawal program in PNE children results in less relapses than after abrupt termination of treatment. In OAB children extended treatment periods improve success rates further, resulting in continence in most of the cases. References (1) A suggested treatment algorithm in nocturnal enuresis with emphasis on partial responders. Neurourol Urodyn 2003: 22: 441-442 (2) An empirical treatment algorithm for incontinent children. J Urol accepted (3) Incontinence 2nd Edition, Health Publication Ltd, Plymouth, 2002; 1086-1089 106 Vermandel A1, Wyndaele J1

1. University Antwerpen WHAT HAPPENS TO CHILDREN WHO HAD BLADDER VOLUME TRAINING FOR REFRACTORY BEDWETTING WHEN THEY GROW UP Hypothesis / aims of study Bedwetting is amongst the most prevalent problems in childhood. Current treatment models generate a three system approach: desmopressin for a deficient diuresis pattern, bladder training and anticholinergic drugs for detrusor overactivity and the enuresis alarm to drill the child to wake in response to wetting himself. We present results in children with refractory monosymptomatic primary nocturnal enuresis (NE) treated with


bladder volume training. We evaluate the importance of normalisation of the bladder capacity and show the longterm results when such children grow into adolescence and adulthood. Study design, materials and methods We included 35 children, 12 girls and 23 boys between 14 and 25 years old who had been treated for NE minimum 5 years ago. No one had daytime incontinence, history of urinary tract infections, urologic or neurologic disease, voiding dysfunction. Nocturnal polyuria was excluded by evaluating nocturnal excretion of solutes and free water. During the original training all had urodynamic testing in the beginning and at the end of the training period. The basic training had been volume training and anticholinergics. When NE persisted despite a bladder capacity of 80% of age expected capacity an enuresis alarm was added to the treatment. Frequency-volume charts were filled in at start and at the end of the training. The actual evaluation consisted of a telephone contact with filling in of the first part of a questionnaire. Supplementary questions and frequency volume charts were sent by mail if participation was agreed. All voided volumes were measured during two days with the fluid intake, the reason to void (sensation or other, 1). Capacity expected for age was calculated by the formula of Hjalmas (2). Results At the time of primary treatment the participants were mean 9,3 years old (6-15years old). Twenty seven had detrusor overactivity. Maximum cystometric capacity changed from 58,5% (33 -74%) to mean 119% (69 – 152%) of the expected capacity for age. Maximum voided volumes noted in the diary changed from mean 47% ( 29 -74%) to mean 120 % (69 – 152%) from age expected capacity. Thirty achieved the age expected capacity. Bedwetting decreased in all and such from mean 6,3 (2-7) per week to mean 3.6 (1/ 2 weeks to 6 / week). No child was completely dry at that stage. Twenty eight used an enuresis alarm for a mean of 4 months. Bedwetting decreased to mean 0,4 per week ( 1/ 4 weeks to 2/ week). At the end of the treatment 24 were dry. But only 11 were able to sleep through the night (8 dry, 3 occasionally bedwetting). The other woke at night from desire to void (16 dry, 8 bedwetting). The contact by telephone was mean 7,7 years (5-10 years) after the original training stopped. Participants were then mean 17,1 years old. Twenty eight were now dry, 5 reported bedwetting twice a month and two others 2-4 times a year. Eighteen were able to sleep through the night, 17 woke up spontaneously. Five refused to fill in diary charts, fearing to relapse, unwilling to be remembered an unpleasant period. Five agreed to participate but filled in too incomplete. The other 25 filled in maximum volumes voided of mean 100% (57 – 211 %) of age expected capacity. The average voided volumes were mean 55 % (29% to 127% ) of expected capacity. Fluid intake was mean 1659 ml ( 990 – 2300 ml). Interpretation of results Capacity training combined with anticholinergics was able to increase bladder capacity in 86% of these children with urodynamically proven detrusor overactivity, too small bladder capacity and persistent bedwetting. However, though most children improved, none became completely dry. With additional bedwetting alarm in those with normalised capacity, 69% became dry. Half of these cured children woke to void at night. When reaching adolescence or young adulthood only 36% had normal capacity and again half stood up at night to void. From those with too small capacity 75 % were dry but most woke up at night. Concluding messages 1. The prevalence of adulthood NE may be higher than written in literature if groups with detrusor

overactivity, small bladder capacity are studied. 2. Bladder capacity training and anticholinergics can increase bladder capacity but do not lead to cure of the

bedwetting in most 3. Children with normal bladder capacity and NE can greatly benefit from bedwetting alarm 4. Stopping of the bedwetting corresponds with spontaneous awakening at night to void 5. Even when normal capacity is reached with training many will fall back in capacity during the yers following

training. This does not correspond with relapse of bedwetting. 6. These data have to be controlled in a larger population. References

1. Neurourol Urodyn 2003; 22: 638-642. 2. Scan J Urol Nephrol 1988; 114: 20-27.


107 De Gennaro M1, Buffa P 2, Capitanucci M L3, Battaglino G F4, Beseghi U 5, Di Lorenzo F 61. Bambino Gesu' Children's Hospital, Departement of Nephro-Urology, Urodynamic Unit , 2. G.Gaslini Children's Hospital, Pediatric Surgery Unit, 3. Bambino Gesu' Children's Hospital, Dept of Nephro-Urology, 4. Ospedale Civile di Vicenza, Pediatric Surgery Unit, 5. Ospedale Generale di Parma, Pediatric Surgery Unit, 6. University of F Bologna, Pediatric Surgery Unit VESICAL AND BOWEL MANAGEMENT AND QUALITY OF LIFE IN SPINA BIFIDA ADULT PATIENTS: RESULTS OF A MULTICENTER ITALIAN SURVEY Hypothesis / aims of study To evaluate vesical and bowel management, continence status and their interference on Quality of Life in adult subjects with Spina Bifida. To obtain a representative sample of the italian population, the multicentric study was started in five third-level Institutions, with patients referred from several areas. Study design, materials and methods An italian multicentric study in adults subjects with spina bifida was started in November 2002. The study was based on an anonymous, self-administered mailed questionnaire. The questionnaire was previously validated on 15 subjects using: test-re-test and missing items analysis; internal consistency analysis, through α index of Cronbach; follow-up (recall). 173 (51% female and 49% male) adult patients with spina bifida answered. The sample was representative of the whole italian territory (prevalent cases estimated: 4000; SEM ± 10%; CI 95%). Attention was directed to: type of spina bifida, associated neurological anomalies as well as major clinical problems related to bladder and bowel dysfunction. Interference of bladder and bowel status on quality of life (QoL) were investigated. The behaviours concerning everyday activities, social life and familial relationship were evaluated. Results Spina bifida was open in 83% of subjects (88% myelomeningocele), associated to hydrocephalus in 91% of cases. Non-walking subjects were 62%. Urinary incontinence ( ≥ 2 episodes/day in 35%, 1 episode/day in 17%, 1 episode/week in 11%) was present in 62% of cases, urinary tract infections occurred in 72% of cases, renal failure in 14%, constipation in 68%, soiling in 54%. Different devices were used: fluff-pulps (31%), pads (43%), drip collectors (8%) and urisheaths (8%). Bladder and bowel dysfunction were self-managed in 61% and 68% of cases, respectively. Bladder management was based on clean intermittent catheterizaton (CIC) in 96% of subjects (self-catheterisation in 82%). CIC was started before 10 years of age in 57% of individuals and anticholinergicagents were associated in 53% of cases. Ninety-one percent of patients were satisfied of CIC. Reasons for satisfaction were: autonomy (61%), easy performance (65%) in different situations (56%), facilitated social life (59%), achieved complete continence (27%). The unsatisfied patients complaining of: pain (9%), persistence of incontinence (36%), lack of autonomy (25%), difficulty (25%). 53% of the unsatisfied patients consider urininary tract infection as a consequence of CIC. Thirty-two percent of individuals were on bowel management program for constipation and soiling using diet (30%), enemas (16%), drugs (9%), anal plugs (4%), others (7%). Satisfaction of bowel management program was reported by 72% of subjects, related to normal bowel movements (59%), easy performance in different situation (31%), facilitated social life (38%), assured continence (17%). The lack of bowel regulation (51%), persistent incontinence (28%), dependence from others (41%), pain (22%), inadequate drugs (62%) and difficulties to perform (6%) were the motivations of patients unsatisfied of their bowel management. Sex, age, social and cultural status were comparable between satisfied and unsatisfied subjects. The major perceived disability affecting QoL was bladder and bowel dysfunction (57% of cases), 26% due to bladder, 11% to bowel and 11 to both dysfunction; while ambulatory impairment was considered the major disability in 25%, sexual problems in 15% and other problems in 3%. Problems arising fom bladder versus bowel control interferred differently into the various everyday activities, except for domestic activities (4%) and family life (10%); travel by public transport (18% bladder versus 19% bowel), nocturnal sleep (20% vs 18%), shopping (26% vs 24%), choice of type of clothes (30% vs 19%), decreased general health (38% vs 39%), sports (46% vs 37%),sexual life (45% vs 37%), mood (48% vs 45%), holidays (47% vs 48%), social outing (49% vs 45%), leisure (51% vs 40%), inability to use public restrooms (57% vs 52%) and travelling (59% vs 53%).


Interpretation of results Bladder and bowel dysfunction are relevant clinical and self-perceived problems in subjects with spina bifida and significantly affect QoL. CIC is performed in the great majority of these patients, starting at different ages. Most patients are satisfied with CIC, but complaints have been referred, mainly about infection and difficult prevention of leakage, with still too frequent use of diapers. Unlike bladder dysfunction, bowel management programs have not been popular so far. Old protocols and scarce attention by physicians and patients to bowel dysfunction might play a role. Moreover, constipation is more easily dealt with by the subjects with different personal strategies. Concluding message Bladder and bowel status with strong implications on QoL are reported in adult population with spina bifida. However, there is evidence that younger patients could greatly benefit from earlier and more careful treatment protocols, with particular regard to bowel dysfunction, which appears undertreated and poorly considered, compared to patient’s perception of disability. 108 Almeida F G1, Schor N1, Leite K1, Srougi M1, Bruschini H1

1. Federal University of Sao Paulo ADIPOSED DERIVED STEM CELLS SEEDED ON THE COLLAGEN MATRIX A NEW EXCITING OPTION FOR TISSUE ENGINEERING RECONSTRUCTION OF THE LOWER URINARY TRACT. Hypothesis / aims of study The urologic reconstructive surgeries are based on autologous organs or tissues transplantation. The harvesting of such tissues is always followed by some sort of morbidity. Skeletal muscle progenitors and autologous in vitro amplified smooth muscle cells has been proposed to repair the impaired tissues, but it still has some inconvenient. Adipose derived stem cells (ADSC) have described to have the ability to differentiate into adiposities, cartilage, bone, neuron and muscle. The ADSC can be used in the urological field as an easy source of cells to be used in urethral and ureteral reconstruction, bladder augmentation, urethral sphincter reconstruction and as injections to urinary incontinence and vesico-uretheral reflux. We describe our initial experience and technique of seeding rat ADSC on collagen based scaffolds (SIS, Cook Urological) that can be used in tissue engineering reconstructions of the lower urinary tract. Study design, materials and methods The 4 months old female rats were anesthetized using a combination of Ketamina and Xylazine to harvest the inguinal fat pad. The inguinal fat was processed as previously described (ref). Briefly, the fat was minced and washed extensively with 1X phosphate buffer saline (PBS). The extracellular matrix was digested with 0.075% collagenase at 37C for 30 minutes in constant agitation. The enzyme was inactivated with equal volume of Dubelco’s modified Eagle media (DMEM) containing 10% fetal bovine serum (FBS). After centrifuge the solution at 250g for 10 min., it is obtained a high density processed lipoaspirate cell pellet. The pellet was ressuspend in DMEM with 10% FBS and an erythrocyte lysis buffer (0.16M NH4Cl) was added for 10 min, and then centrifuged again. The pellet was re-suspended and plated in 100mm dishes at the concentration of 1X105. The cells were cultured in DMEM supplemented with 10% FBS (CM) until reach confluence. Once the cells reached the confluence they were seeded on commercial collagen based scaffold- SIS (0,5 x 1,0 cm ) at the concentration of 1X106. The cells were grown on these scaffolds and then evaluated regarding the distribution, viability and morphology. Results To obtain a cell coated SIS. The SIS was re-hydrated during 1 hour in sterile PBS and placed into a 100mm culture dishe. Using only 30 micro-litters of CM, 1X106 cells were re-suspended and seeded on the SIS (0,5 x 1,0 cm ). Two ml of CM were added to the dish, which just embedded the SIS, but did not cover it preventing cells floating. After 12 hours of incubation, the media was changed carefully to avoid cell floatation. With 24 hours the cells were attached to the SIS allowing addition of extra media, which were changed every other day. The cells stabilized and remained viable for 4 weeks, spreading over the SIS allowing differentiation and/or in vivo transplantation.


Interpretation of results The ADSC have a unique characteristic of been a harvested in a expendable tissue with minimal morbidity and possessing a multi potent cell lineage differentiation ability. These cells have been demonstrated to be stable in culture, with low senescence rate, which allows great expansion in vitro and suggests that ADSC can very encouraging option for tissue engeneering. This study is to demonstrate the possible applicability of ADSC on urological reconstructions by seeding these cells on extra cellular matrix ( ECM) or even in synthetic scaffolds (i.e.; PLA and PLGA). The ability to differentiate into different tissues of ADSC, will lead us to study the potential of ADSC on urological reconstructions by seeding this cells on scaffolds and transplant them before or after differentiation. Concluding message ADSCs are an easy source of cells that can be used for several modalities of urinary tract reconstruction providing an alternative source of cells for tissue engineering. The fat procurement process is simpler than other sources of mesenquimal stem cell and the capacity of these cells to differentiate into skeletal, smooth muscle, and nerve makes their use ideal for reconstruction of the urinary tract. 109 Hayashi Y1, Birder L1, de Groat W1, Epperly M1, Peterson J1, Greenberger J1, Meyers S1, Zeidel M1, Kanai A1 1. University of Pittsburgh INHIBITION OF MITOCHONDRIAL NITRIC OXIDE SYNTHASE DURING PELVIC IRRADIATION PREVENTS UROTHELIAL DAMAGE AND PROTECTS THE BLADDER AGAINST RADIATION CYSTITIS Hypothesis / aims of study Radiation therapy for pelvic malignancies can cause bladder cystitis resulting in decreased compliance, reduced capacity and the symptoms of frequency, urgency, and dysuria. Furthermore, the potential to develop radiation cystitis prevents the use of radiation therapy to treat bladder cancer and limits the radiation dose that can be used to treat other pelvic malignancies. The mechanism of radiation cystitis has not yet been described, but our findings suggest that it may involve radiation-induced activation of urothelial mitochondrial nitric oxide synthase (mtNOS), disruption of the urothelial permeability barrier, and exposure of the underlying tissues to urine. We propose that radiation-induced activation of mtNOS results in prolonged mitochondrial NO production which inhibits the respiratory chain and thereby increases superoxide (O2

-) generation. Superoxide, in turn, reacts with manganese superoxide dismutase (MnSOD) to form hydrogen peroxide (H2O2) and/or with NO to form peroxynitrite (ONO2

-), both of which can damage the urothelium leading to necrotic and apoptotic cell death and disrupt the permeability barrier (Fig 1). Accordingly, our aim was to inhibit mtNOS during irradiation and determine if we could protect the bladder urothelium and prevent the development of radiation cystitis.


Study design, materials and methods We have developed a mouse model of radiation cystitis where single- or fractionated-dose irradiation results in decreased transepithelial resistance and increased urea and water permeabilities within 24 hrs following final radiation exposure. At six months, bladders exhibit non-voiding contractions, increased baseline pressures and decreased bladder compliance indicative of radiation cystitis in humans. Mice were irradiated with 10 or 50 Gray (Gy; 1Gy = 1 J/kg = 100 rads) fractions to the bladder to a total of 50 Gy. The following preparations were used: 1) Wild-type (WT) mice; 2) WT mice whose bladders were transfected with the transgene for human manganese superoxide dismutate (MnSOD; a mitochondrial scavenger of O2

-), 3) WT mice with a nitric oxide synthase (NOS) antagonist (L-NMA; 500 µM) in the bladder lumen during irradiation; and 4-5) nNOSα-/- (the isoform of mtNOS) or eNOS-/- mice. Twenty-four hours after the end of the radiation regimen, bladders were excised and placed in an Ussing chamber for measurements of transepithelial resistance (TER) and water and urea permeabilities, or placed in a muscle bath for simultaneous microsensor measurements of NO and ONO2

- production in the urothelium.

Results Irradiation of the bladder resulted in decreased TER (Fig 2a) and increased urea (2b) and water (2c) permeabilities. Prior transfection with human MnSOD partially protected the urothelium resulting in a smaller decrease in TER (2a) and smaller increases in urea (2b) and water (2c) permeabilities. However, the presence of L-NMA in the bladder lumen during irradiation resulted in almost complete protection of the bladder urothelium (2a-c). The involvement of the urothelium in radiation-induced damage was demonstrated in scanning electron micrographs (SEMs) where irradiated bladders show selective destruction of the umbrella cell layer (2e) compared to normal urothelium (2d). However, in MnSOD transfected bladders (2f) the disruption of the urothelium is markedly decreased and in an L-NMA protected bladder, the urothelium looks like the control (not shown). To further test the hypothesis that ionizing radiation activates mtNOS, we irradiated the bladders of nNOSα-/- and eNOS-/- mice. While the decrease in TER (2g) and increases in urea (2h) and water (2i) permeabilities of eNOS-/- were comparable to those seen in irradiated wild-type mice, the bladders of nNOSα-/- mice were radioprotected with barrier properties similar to non-irradiated WT mice (2g-i). As further support, direct microsensor measurements from the urothelial surface of excised bladders revealed that NO production


(evoked with capsaicin; a normal response) resulted in a concomitant production of ONO2- (an abnormal

response indicating excessive O2- levels) in unprotected irradiated bladders. The NO evoked formation of

ONO2- was not seen in non-irradiated bladders or irradiated ones overexpressing MnSOD or protected with L-

NMA (not shown). All experiments were carried out in n≥6 bladders. Interpretation of results SEMs demonstrate that ionizing radiation selectively disrupts the urothelium. Mitochondria are implicated since MnSOD is localized there and is partially protective. MnSOD is partially protective because it steals O2

- from NO preventing the formation of highly reactive ONO2

- and increasing the formation of the less reactive but still potentially damaging H2O2. Inhibition of mtNOS on the other hand prevents the formation of both ONO2

- and H2O2 (see Fig 1). This theory is further supported by the formation of ONO2

- in irradiated bladders, but not in irradiated bladders protected with MnSOD or L-NMA. Concluding message These data suggest that ionizing radiation activates the mtNOS in the urothelial cells lining the bladder lumen. This results in the disruption of the urothelial permeability barrier leading to the development of radiation cystitis. Thus, the transfection of the urothelium with the human MnSOD transgene prior to irradiation, or better still, the presence of a NOS antagonist in the lumen during irradiation, protects the bladder against radiation cystitis and offers a potentially clinically relevant treatment for the prevention of radiation cystitis. FUNDING: NIH - NIDDK 110 Thakar R1, Andrews V1, Sultan A1

1. Mayday University Hospital OBSTETRIC ANAL SPHINCTER INJURY (OASI) REPAIR- A PROTOCOL WITH A DIFFERENCE? Hypothesis / aims of study Anal incontinence occurs in up to 5% of vaginal deliveries in the United Kingdom. It is a serious and debilitating condition that is under-reported because of embarrassment and associated social stigma. Obstetric anal sphincter injury is the major cause of anal incontinence. Despite primary repair 85% of women have persistent sonographic defects1. Anal incontinence following obstetric anal sphincter injury occurs in 40% of women after a primary anal sphincter repair.2 Aim: To determine whether strict adherence to a recommended repair protocol3 can reduce the incidence of anal incontinence following obstetric anal sphincter injury. Study design, materials and methods All women who had an obstetric anal sphincter injury were managed according to the protocol in the following way:

1. All repairs were conducted in theatre 2. All repairs were conducted by obstetricians experienced in anal sphincter repair who had attended a

hands-on training workshop or by obstetricians under supervision. 3. A special perineal repair instrument tray was used for the repair which contains a Weislander self

retaining retractor, four Allis tissue forceps, McIndoe scissors, tooth forceps, four artery forceps, stitch scissors and needle holder.

4. Tears which are classified as 3a where less than 50% of the external anal sphincter is disrupted were repaired by the end to end technique.

5. When the tears are classified as 3b where more than 50% of the external anal sphincter is disrupted, the external anal sphincter is completely divided and repaired by the overlap technique.

6. The internal sphincter was identified and repaired separately when damaged. 7. The internal and external anal sphincter was repaired using 3/0 PDS. 8. All women were given intravenous antibiotics at the time of repair and had oral antibiotics continued for

a week. 9. All patients received lactulose and fybogel for two weeks.


Women completed a validated Manchester questionnaire relating to bowel symptoms before delivery and also a second questionnaire at eight to twelve weeks after repair when patients were followed up in a dedicated one-stop perineal clinic. At follow up all women had anal endosonography and manometry performed. Results During a 16 month period 83 obstetric anal sphincter injuries occurred (prevalence 1.6%). Of these 73(88%) were in primigravid women and 30 (36.1%) followed an instrumental delivery. 37 of the 45 (82.2%) with obstetric anal sphincter injury involved >50% external anal sphincter thickness and all had an overlap repair. Six were repaired by consultants and the remainder were repaired at delivery by the duty registrar.There were 11 internal sphincter injuries (3c and 4th degree). 8 (72%) were successfully repaired and were aymptomatic. Three had persistent internal sphincter defects on scan. The description of tears, symptoms, anal endosonography, manometry are outlined in Tables 1-4. Table 1: Description of 3rd and 4th degree tears Not classified / missed 4(4.8%) 3a <50% External anal sphincter involved 34(41.0%) 3b >50% External anal sphincter involved 34(41.0%) 3c Internal anal sphincter involved 5(6.0%) 4 Anal mucosa involved 6(7.2%) TOTAL 83 Table 2: Anal incontinence symptoms: antenatal Follow-up

Liquid/solid incontinence 0 0 Flatus incontinence 8(9.6%) 7(8.4%) p=0.79

Urgency 6(7.2%) 2(2.4%) p=0.15 Table 3: Anal endosongraphy six weeks after repair Intact sphincter 70(84.3%) < 1 quadrant defect 11(13.3%) >1 quadrant defect 4(4.8%) Table 4: Anal manometry(mmHg) six weeks after repair Resting pressure 3a/3b 51.5(29-95) ] p=0.018 3c/4 43(31-52) ] Squeeze pressure 3a/3b 80.5(20-143) ] p=0.008 3c/4 69.5(45-79) ] There was a significant correlation between resting pressure measurements and defects (p=0.005). Interpretation of results This study demonstrates that anal incontinence and residual sphincter defects can be significantly reduced when this protocol is adhered to by trained doctors. In addition with more extensive anal sphincter injury anal manometric pressures are significantly lower. Unlike secondary sphincter repair, his study confirms the benefit of identifying and repairing internal sphincter injury as 72% had no persistent defect and were asymptomatic. Concluding message Implementation of this protocol nationally would have a dramatic impact on the prevalence of anal incontinence and consequently improve women’s quality of life. All units should carefully audit their own outcomes to establish whether a change of practice is required. References 1. Third degree obstetric anal sphincter tears: risk factors and outcome of primary repair. BMJ 1994; 308:887-91. 2. Lower genital tract and anal sphincter trauma. Best Practice & Research – Clinical Obstetrics and Gynaecology 2002;16(1):99-116 3. Management of obstetric anal sphincter injury. The Obstetrician and Gynaecologist. 2003: 5(2): 72-78.


111 Balmforth J 1, Bidmead J 1, Cardozo L1, Hextall A1, Kelvin B1, Mantle J 11. Kings College Hospital RAISING THE TONE: A PROSPECTIVE OBSERVATIONAL STUDY EVALUATING THE EFFECT OF PELVIC FLOOR MUSCLE TRAINING ON BLADDER NECK MOBILITY AND ASSOCIATED IMPROVEMENT IN STRESS URINARY INCONTINENCE Hypothesis / aims of study Pelvic floor muscle training (PFMT) has been demonstrated in a number of randomised controlled trials to be effective in the treatment of stress urinary incontinence. Several theoretical rationales have been proposed to explain the efficacy of PFMT [1]. The purpose of this study was to assess the impact of PFMT on bladder neck mobility and to correlate any observed changes to objective, standardised outcome measures of stress urinary incontinence severity.

Study design, materials and methods Local ethics committee approval was obtained prior to commencing the study. Women were recruited prospectively over a three year period. The study population comprised 97 treatment naïve women (mean age=49.5, SD=10.6) drawn from patients referred to a tertiary centre with symptoms of stress urinary incontinence and subsequently diagnosed as having ‘mild’ to ‘severe’ urodynamic stress incontinence on videourodynamic assessment. An intensive, 14 week programme of ‘pelvic floor rehabilitation’ consisting of an individualised PFMT programme and behavioural modification was taught, administered and monitored by an expert physiotherapist, as part of a large prospective trial evaluating PFMT. Bladder neck mobility on perineal ultrasound was assessed immediately prior to, and on completion of the 14 week programme. Analysis was performed by using calliper tracing and an x-y coordinate system [2] to calculate the angle of bladder neck rotation, with 0 degrees defined from the inferoposterior margin of the pubic symphysis. An initial scan was performed at rest and several subsequent scans performed to measure maximum bladder neck displacement with valsalva and maximum elevation on pelvic floor squeeze. Maximum excursion and incursion were taught by use of biofeedback. Using the real-time ultrasound image, the women were coached to produce consistent maximum movement over several attempts. Treatment outcome was assessed using a standardised pad test (bladder volume 250mls with a 30 min exercise programme) and a condition-specific validated Quality of Life questionnaire: The Kings Health Questionnaire (KHQ). Results

-50

-25

0

25

50

75

100

Scatterplot showing distribution and mean bladderneck angle pre and post-treatment

VALSALVA SQUEEZE

POSITION AT REST

REST Pre-Tx PostTx Pre-Tx Post-Tx Pre-Tx Post-Tx

Bladder neck mobility

Bla

dder

nec

k an

gle

rela

tive

toin

fero

post

erio

r m

argi

n of

sym

phas

is p

ubis


TABLE 1: Changes In Bladder Neck Angle Pre and Post-PFMT

pre-PFMT post-PFMT Bladder neck angle (Relative to inferoposterior marginof symphysis pubis) Mean 95% CI Mean 95% CI

Mean of diff.

P value (Paired-t test)

At Rest 48.1° 44.0 52.1

55.4° 51.7 59.1

-6.6 0.009

Maximum Valsalva 22.3° 16.1 28.5

35.2° 29.1 41.4

-11.7 0.002

Maximum Pelvic Squeeze 53.3° 47.6 58.9

63.7° 58.3 69.1

-8.4 0.013

TABLE 2: Changes in Pad test and KHQ Domains Pre and Post-PFMT

pre-PFMT post-PFMT

Parameter Mean 95% CI Mean 95% CI

P value (Wilcoxon Signed Rank)

Pad test (g) 12.2 8.25 - 16.1 5.44 2.64 - 8.24 <0.001 GHP (%) 27.7 24.3 - 31.0 26.8 22.7 - 30.9 0.413 II (%) 57.4 51.9 - 62.8 43.8 38.0 - 49.6 <0.001 RL (%) 37.6 31.1 - 44.0 19.6 14.4 - 24.7 <0.001 PL (%) 42.7 37.3 - 48.1 30.5 25.2 - 35.7 <0.001 SL (%) 18.2 12.9 - 23.6 10.7 6.76 - 14.6 0.009 PR (%) 23.8 16.7 - 30.9 19.4 11.8 - 27.0 0.736 E (%) 33.5 28.0 - 38.9 26.6 21.1 - 32.2 0.006 SE (%) 35.2 30.2 - 40.1 30.5 25.8 - 35.1 0.023

KH

Q D

OM

AIN

S

SM (%) 45.7 40.4 - 51.1 42.5 36.6 - 48.3 0.321 Interpretation of results The position of the bladder neck was observed to be significantly elevated at rest, valsalva and squeeze on post-treatment assessment. Interestingly, the magnitude of the bladder neck incursion observed at ‘maximum squeeze’ and excursion at ‘maximum valsalva’ was found to increase and decrease respectively, compared to pre-treatment values. This suggests that PFMT brings about an increase in the resting tone of the pelvic floor in addition to improving elevation on voluntary contraction and reducing displacement on straining. Pad test leakage and six out of the nine KHQ domains were significantly improved, following treatment. However, there was no significant correlation between the reduction in individual women’s pad loss and any of the ultrasound parameters measuring changes in bladder neck mobility. This perhaps reflects the likelihood that improved levator resting tone and increased support of pelvic viscera is not the only mechanism by which urinary leakage is reduced and QoL improved. There are several other potential factors that may be significant. These include, hypertrophy of the levators leading to modified muscle morphology, an improvement in neuromuscular function and behavioural adaptations leading to voluntary contraction of the pelvic floor before and during increases in intra abdominal pressure – “The Knack” [3].

Concluding message Treatment with a 14 week intensive package of PFMT and behavioural modification resulted in a statistically significant elevation of the bladder neck at rest, maximum pelvic floor contraction and maximum valsalva. This is associated with a statistically and clinically significant reduction in urine loss and improvement in condition-specific Quality of Life. The results of this study reinforce previous published work showing that PFMT is an effective treatment for stress urinary incontinence and provide an important new insight into how functional pelvic anatomy may be modified by this widely used intervention.

References 1. Pelvic floor muscle training is effective in treatment of female stress urinary incontinence, but how does it work? Int Urogynecol J

Pelvic Flor Dysfunct. 2004; 15(2): 76-84. 2. Levator ani function before and after childbirth. BJOG 1997; 104: 1004-1008. 3. A pelvic muscle precontraction can reduce cough-related urine loss in selected women with mild SUI. J Am Geriatr Soc. 1998;

46(7): 870-874.


112 Féra P1, Glashan R1, Lelis M A1, Gonzales S R1, Nogueira M D P1, Almeida F1, Srougi M1, Bruschini H1 1. Federal University of São Paulo IMMEDIATELY OUTCOME OF DDAVP VERSUS BEHAVIOURAL MODIFICATION FOR TREATMENT OF MONOSYMPTOMATIC NOCTURNAL ENURESIS: A PROSPECTIVE RANDOMIZED STUDY OF 30 PATIENTS Hypothesis / aims of study The therapeutic options for Monosymptomatic Nocturnal Enuresis (MNE) include the use of medications and behavioral modifications. Many studies demonstrate the effectiveness of the use of Desmopressin in a variety of doses and forms of administration (1). We have previously demonstrated the efficacy of behavioral modification on a great number of children (2). In our experience, it seems that the patient and parents adherence to the treatment is related to how fast the first line therapy improves the children’s symptoms. In this study, we compare the use of DDAVP and behavioural modifications (BM) in monosymptomatic nocturnal enuresis as a first line treatment. Study design, materials and methods We performed a prospective randomized study of outpatient children with diagnostic of primary MNE from May 2002 to February 2004. Patients with no previous treatment were randomized into two groups: A) Patients treated with DDAVP; B) Patients treated with behavioural modification. The DDAVP treatment was performed titrating the dose to a maximum of 0.4 mg at bed time. Children treated with BM were submitted to a previously described association of different modalities of BM (2), such as, dietary and fluid adjustments, voiding schedules, double voiding, bedtime toileting, alarm clock once at night, pelvic floor training, environmental modifications, changes in parent’s attitudes, improvement of self-esteem, self-care. All patients filled a 14 days nocturnal diary before initiate the treatment and were instructed to keep filling this diary every night during the 30 days of treatment. The analysis were performed considering the bedwetting episodes in the last 14 days of treatment. Results Thirty children with mean age of 9.2 +/- 1.8 years old were evaluated. The two randomized groups were matched for age, gender and pre treatment number of bedwetting episodes (Table 1). The improvement on bedwettings episodes on the two groups is shown on table 2. Age or gender was not related to the improvement. It was observed that 46.6% and 53.3% of the children presented improvement of 50% or more on the bedwetting episodes and 30% and 6% had completely failed (no improvement at all), respectively on the DDAVP and BM groups. Comparing the two groups, patients treated with BM had a greater decrease the number of bedwetting episodes than the DDAVP group (Table 2; p=0.029).

Table 1: Comparison of age, gender and pre treatment bedwetting episodes in two groups

Group A Group B Total p Age (mean ± SD)

9.53 ± 2.16 8.93 ± 1.48 9.23 ± 1.85 0.486

Gender – N (%) Male Female

12 (80%) 3 (20%)

9 (60%) 6 (40%)

21 (70%) 9 (30%)

0.232

Pre treatment bedwetting episodes (mean ± SD)

9.87 ± 2.90 8.93 ± 3.88 9.40 ± 3.40 0.539


Table 2: Comparison of pre and post treatment bedwetting in the two groups.

Pre treatment (mean ± SD) Post treatment (mean ± SD) p Group A (DDAVP)

9.87 ± 2.90 7.27 ± 4.00 0.047

Group B (BM)

8.93 ± 3.88 3.93 ± 3.32 0.003

Total 9.40 ± 3.40 5.60 ± 3.99 0.0005 Interpretation of results The results show that both therapeutic options offer similar improvement of bedwetting episodes in a short term treatment. However, the BM presents lower chance of completely failure when compared to DDAVP. The results with BM could be optimized if performed for longer period as previously shown in a study with a 4 months treatment (2). The association of different modalities of BM could be improved by adding the DDAVP on the first approach. Further studies should be performed to evaluate the long term efficacy, adherence and the effects of the association of BM and DDAVP. Concluding message In a short term follow-up, both therapeutic approaches isolated promote improvement in bedwetting episodes, with lower failure rate favoring the BM in comparison to DDAVP. As both treatments generated good improvement, the concomitant use of both therapies, at least in the initial approach, could maximize the bedwetting reduction, which would motivate patient and parents to persist the treatment. In a second period, the treatment can be individualized according to the facilities and preferences. References

1. Desmopressin for nocturnal enuresis in children (Cochrane Review) In: The Cochrane Library, Issue 4, 2002.

2. Behavioral interventions in primary enuresis: experience report in Brazil. Urologic Nursing, v 22, n 4, 257-262, 2002.

113 Mellier G1, Moore R2, Jacquetin B3 1. Hôpital Edouard Herriot, 2. Atlanta Urogynecology Associates, 3. Maternite Hotel Dieu A META-ANALYSIS OF THE INTRA-OPERATIVE SAFETY AND EFFECTIVENESS OF THE TRANSOBTURATOR HAMMOCK SEEN IN RESULTS OF TWO PROSPECTIVE STUDIES IN 9 COUNTRIES WITH 204 PATIENTS Hypothesis / aims of study For years, women with urinary incontinence have had the treatment option of a minimally invasive procedure that placed tension-free vaginal tape sub-urethrally with a relatively high degree of success. However, while rare, bladder and bowel perforations, as well as vascular injuries are possibilities with this treatment modality due to the blind passage of needles through the retropubic space. To address this concern, a new surgical approach which passes the needles through the trans-obturator foramen while still placing polypropylene mesh sub-urethrally has been introduced. We are reporting on a meta-analysis of a combined sample of 204 women in 9 countries in Europe, Australia, and North America who participated in two studies on the efficacy and safety of the Monarc Subfascial Hammock Sling System (American Medical Systems). Study design, materials and methods Common data points between two studies with similar protocols were analyzed. Improvement rates were measured pre- and post-op by: physician and patient report, quality of life measures (IIQ-7 and the UDI-6), pad use per day, cough stress test, and finally, one-hour pad weight test. The follow-up range in the smaller study


(taking place in the U.S. only) is 4-8 weeks, 6 months, and 12 months. The follow-up range in the larger study (the remaining 8 countries) is 4-6 weeks, 3 months, 6 months, 12 months and 24 months. 204 women (mean age of 56.5 years) enrolled in the study between January 2003 and March 2004; operative data was gathered on 193 of these participants. Most had some form of stress incontinence: 145/204 (71.1%) had stress and 54/204 (26.5%) had mixed incontinence. Of the remaining participants, 2/204 (1.0%) had urge incontinence and 3 (1.5%) were unreported. Incontinence was present for an average of 8.4 years, and pad use was reported as 3.0 pads/day (mean). Pre-operative diagnostics tests consisted of the cough stress test and the one-hour pad weight test. Of the 200 women who took the cough stress test, 181 (90.5%) tested positive. Among the 191 women who consented to the one-hour pad weight test, the average pad weight gain was 57.2g. Results The mean operative time for sling placement only was 10.6 minutes. Blood loss was minimal (mean of 35ml), and the time to urinate without a catheter was 10.3 hours. The majority of patients, 180/193 or 93.3% (with 8/193 or 4.1% unreported) went home without a catheter. Positive results on the cough stress test dropped from 181/200 (90.5%) pre-op to 7/77 (8.2%) at 6 months. Pad use per day dropped from 8.4 pads/day pre-operatively to 0.5 pads/day at the 4-8 week and 6 month follow-up. Physician and patient assessment of continence, defined as completely dry or substantially continent, was 90.6% and 89.6% respectively at 4-8 weeks, and 85.7% and 82.5% respectively at 6 months. 44 complications that could possibly have been related to the device were reported in 22 patients (22/193, or 11.4% of patients).

Specific complications included:

UTI’s 9 (4.7%) Urge symptoms 7 (3.6%) Increased residual urine 5 (2.6%) Urinary retention 4 (2.1%) Recurrent incontinence 3 (1.6%) Groin pain 3 (1.6%) Cystitis symptoms 2 (1.0%) Acute urinary retention 2 (1.0%) Urge incontinence 2 (1.0%) Vaginal erosion 2 (1.0%)

Device malfunction, dyspareunia, vaginal discharge, vaginal infection, and musculoskeletal pain were each reported in 1/193 patients (0.5%). 6/193 patients (3.1%) had surgical revisions to release sling tension, remove slings, or replace the sling; four due to continual urinary incontinence, one due to retention, and one due to vaginal erosion. Interpretation of results The transobturator approach was designed to address concerns of intra-operative injuries which have been reported with sling treatments passed through the retropubic space. Of the 193 patients for whom we have intra-operative data, zero had bladder, bowel, or vascular perforations. Both objective and subjective criteria points gathered post-operatively showed improvement; these included pad use per day, cough stress test, one-hour pad weight test, and physician and patient assessment. Concluding message This important meta-analysis combines data from Australia, Belgium, Canada, France, Germany, Italy, Spain, the United Kingdom, and the United States and represents the largest prospective study to date on the transobturator procedure. The Monarc Subfascial Hammock appears to be a safe, effective procedure for sub-urethral sling placement. FUNDING: American Medical System


114 Gandhi S1, Kwon C2, Goldberg R P1, Abramov Y1, Beaumont J L3, Koduri S1, Sand P K1

1. Evanston Continence Center, Northwestern Univ Feinberg School of Med, 2. Div of Urogynecology, New York Univ School of Med, 3. Center on Outcomes, Research, and Education, Evanston Northwestern Healthcare A RANDOMIZED CONTROLLED TRIAL OF FASCIA LATA FOR THE PREVENTION OF RECURRENT ANTERIOR VAGINAL WALL PROLAPSE Hypothesis / aims of study Genital prolapse is a common problem with an especially high prevalence among parous women. Successful treatment of anterior wall prolapse remains challenging. Recurrent anterior wall prolapse has been reported to occur in up to 70% of women undergoing standard colporrhaphy (1). We conducted this study to evaluate the efficacy of solvent dehydrated cadaveric fascia lata in preventing recurrent anterior vaginal wall prolapse during reconstructive surgery. Study design, materials and methods A prospective, randomized, controlled trial evaluating the impact of a 2x4 cm patch of solvent dehydrated cadaveric fascia lata on recurrent anterior vaginal wall prolapse was performed in women with anterior vaginal wall prolapse to the hymenal ring and beyond. Subjects were randomized to standard colporrhaphy with or without a fascial patch. The patch was sutured in place between the plicated endopelvic connective tissue and vaginal epithelium. Subjects were evaluated by both the Baden-Walker modified halfway and POP-Q systems preoperatively and at 2, 6, 12, 52 weeks postoperatively. Patients were also asked to return for follow-up beyond 1 year. “Failure” was defined as either ICS stage II anterior wall prolapse or prolapse to the introitus. This IRB-approved study was powered to detect a 15% difference in recurrent anterior wall prolapse. Groups were compared using chi-squared or Fisher’s exact tests. Multiple logistic regression analysis was used to control for potential confounding variables. Results Of 162 subjects enrolled from July 1999 to November 2002, 154 subjects had surgery (76 patch: 78 no patch). 134 subjects (87%) returned for either a 52 week or long term evaluation. The two groups were similar for age, history of previous reconstructive surgery, and concomitant surgeries. Mean age (SD) was 65.2 years (11.6). At entry, 76 patients (49%) had ICS stage II, 72 patients (47%) had stage III, and 6 patients (4%) had stage IV anterior vaginal wall prolapse. Twenty of 68 controls (29%) and 15 of 66 subjects (23%) in the patch group experienced recurrent stage II or greater anterior wall prolapse (p=0.379). When defining recurrent prolapse as anterior wall descent to the introitus or beyond, 9 of 69 controls (13%) and 8 of 66 subjects (12%) in the patch group experienced recurrent prolapse (p=0.872). 74% with recurrent prolapse were free of symptoms. In multiple logistic regression analysis, a fascial patch did not reduce recurrent anterior vaginal wall prolapse (OR 0.70, p=0.380), while the presence of a transvaginal sling was associated with a dramatic decrease in recurrent stage II anterior wall prolapse (OR 0.119, p<0.0001). Interpretation of results The use of solvent dehydrated fascia lata as a barrier during anterior colporrhaphy does not appear to decrease the rate of recurrent prolapse. This study demonstrates a significant protective effect of transvaginal slings against recurrent anterior wall prolapse. Concluding message Surgeons should use adjuvant grafts in reconstructive surgery with caution until efficacy is demonstrated in randomized controlled trials. Future studies on the impact of adjuvant grafts in the anterior compartment should include a stratified randomization for transvaginal sling. References

1. Anterior colporrhaphy: A randomized trial of three surgical techniques. Am. J Obstet Gynecol 2001; 185: 1299-306.

FUNDING: Mentor Corporation


115 Fitzgerald M P1, Brown J S2, Wassel Fyr C2, Brubaker L1, Thom D2, Van Den Eeden S K3, Subak L L2, RRISK study group.21. Loyola University Medical Center, 2. University of California at San Francisco, 3. Kaiser Permanente California DOES A HISTORY OF CHILDHOOD URINARY SYMPTOMS PREDICT ADULT SYMPTOMS? Hypothesis / aims of study Although anecdotal evidence supports an association between a history of childhood urinary tract symptoms and current lower urinary tract symptoms, there are few population based studies that support this association. Our objective was to describe the association between childhood symptoms and current adult urinary lower urinary tract symptoms in a sample of American women. Study design, materials and methods The Reproductive Risks for Incontinence Study at Kaiser (RRISK) study included members of a large health maintenance organization, Kaiser Permenente Medical Care Program of Northern California who were enrolled in a cohort of 2109 women aged 40 to 69 when they were randomly selected from age and race strata. In-person interviews were conducted to ascertain childhood history of urinary frequency, urinary incontinence (UI), and multiple urinary tract infections (UTIs) and describe current symptoms of daytime and nighttime urination frequency, urinary urgency and multiple UTIs in the past year. Participants were asked to ‘think back to the period of your life between first grade and high school’ and report how often each of the following happened: ‘Frequent urination during the day’, ‘Accidental leakage of urine during the day’, ‘Frequent urination after going to bed’, ‘Accidental leakage of urine in bed’, and ‘More than one bladder or kidney infection a year’. Participants were defined as having a specific childhood urinary symptom if they responded ‘sometimes’ or ‘often’. Current urinary incontinence and urinary urgency were defined as self-report of monthly or grater incontinence or urgency in the past 12 months. Recurrent UTI was defined as self-report of a doctor telling the participant she had a urinary tract infection at least twice during the prior 12 months. Current daytime and nighttime urinary frequency was defined as self-report of > 7 and > 1 voids per day and night, respectively, during the last 12months. Logistic regression was used to estimate the odds ratio and describe the 95% confidence intervals for evaluate the association between childhood urinary tract symptoms and current urinary symptoms while adjusting for age, race/ethnicity and body mass index. Results The 2109 participants were racially diverse (48% White, 18% Black, 16% Latina, and 16% Asian) with a mean age of 56 + 9 years. The frequency of current and childhood urinary symptoms is detailed in Table I.

Table I: Subjects reporting urinary symptoms. Current Urinary Symptom Number (%) Urinary incontinence at least monthly 899 (43%) Urinary incontinence at least weekly 603 (29%) Daytime urinary frequency >7 daily 501 (24%) Nighttime urinary frequency >1 nightly 638 (30%) Childhood Urinary Symptom Frequent urination during the day 299 (14%) Accidental leakage of urine during the day 103 (5%) Frequent urination after going to bed 220 (10%) Accidental leakage of urine in bed 164 (8%) More than one bladder or kidney infection a year 100 (5%)

Frequent daytime urination in childhood was strongly associated with current urgency (OR=1.8, p<0.001), and weakly associated with both daytime (OR=1.4, p=0.07) and nighttime (OR=1.5, p=0.06) adult frequency. Frequent nighttime urination in childhood was strongly associated with current nighttime frequency (OR=2.4, p<0.001). A history of UTIs in childhood was also associated with current nighttime frequency (OR=1.7, p=0.04) and current UTIs (OR=2.6, p<0.001). Childhood symptoms were not associated with current urinary incontinence.


Interpretation of results Data from the RRISK cohort support an association between recall of childhood urinary frequency and current urgency and urinary frequency. One explanation for this association may be that physiologic characteristics underlying overactive bladder symptoms in children, may persist to adulthood. Future research may reveal whether treatment of childhood disorders can prevent adult symptoms. Concluding message Our analysis confirms an association between childhood and adult lower urinary tract symptoms. FUNDING: NIDDK R01-#53335 116 Donaldson M1, McGrother C 1, Thompson J 1, Matthews R1, Dallosso H 11. University of Leicester THE NATURAL HISTORY OF URINARY STORAGE DISORDER IN OLDER WOMEN IN THE COMMUNITY; A THREE YEAR PROSPECTIVE COHORT STUDY Hypothesis / aims of study The ICS suggests that within the overall group of urinary storage symptoms there exist the distinct syndromes of Overactive Bladder (OAB) and Stress Urinary Incontinence (SUI) linking to the underlying conditions of Detrusor Overactivity (DO) and Urodynamic Stress Incontinence (USI) (1). The two syndromes OAB and SUI show different patterns of prevalence with age (2,3); the prevalence of OAB rises with age while that of SUI does not, suggesting their natural histories (i.e. changes in average severity of cases with advancing age) may also differ. This study aims to develop and validate symptom severity scores and describe the natural history patterns for these recognised syndromes. Study design, materials and methods Two separate but related studies were involved (i) a prospective cohort study (N=12,750) with baseline measures and 3 years of follow-up and (ii) a clinic sample (N=2052) from a randomised controlled trial. Subjects were community-living women aged 40 or more, approached using postal questionnaires. Measures included standardised urinary symptoms of frequency, nocturia, urgency and leakage. From the clinic sample, symptom category and severity scores were derived for SUI and OAB from weightings obtained from logistic regression models of symptoms in relation to urodynamic (UD) diagnoses and severity scores were validated against 24-hour pad test and 3-day diary measures. Categorisation models predicted USI with a sensitivity and specificity of 76.9% and 56.3% respectively, and DO with a sensitivity and specificity of 63.1% and 65.1%. In the prospective cohort, the syndromes were categorised using the logistic regression models developed in the clinic sample. Mean severity scores for each syndrome were then plotted in each 10-year age band for baseline and 3 years of follow-up, to demonstrate the changes in severity with age of the two syndromes. Results Symptoms included in the OAB severity score were: frequency of urge leakage; frequency of micturition; nocturia; and strength of urgency. Symptoms in the SUI severity score were frequency of stress leakage and amount of leakage. OAB and SUI severity scores showed the expected relationships with relevant clinical measures. SUI showed a stronger relationship with volume than did OAB, while OAB showed a strong correlation with frequency and SUI showed none. The severity of SUI showed a peak around age 60 followed by a decline and another peak in old age but little evidence of age related progression (Figure). The severity of OAB demonstrated an age-related progression accelerating in the 60’s age group and continuing to rise through the 70’s and 80’s. SUI severity showed considerably more variation between follow-ups than OAB severity. Interpretation of results These contrasting patterns of progression are consistent with SUI and OAB representing different conditions and suggest different aetiological processes. For example, the age-specific peak in the severity of SUI


coincides with the population peak for obesity, a recognised risk factor for SUI. The acceleration of OAB severity in the 60’s age group also coincides with the steep increase in prevalence of type II diabetes, a specific risk factor for OAB. The categorisation method used in this study has the advantage of relating symptoms to the gold standard of UD diagnoses thereby providing a greater degree of accuracy, although there is some residual misclassification indicated by the levels of sensitivity and specificity. In addition, the severity scores were composed of symptoms weighted according to their relationship with UD giving more emphasis to symptoms with the strongest, positive relationships.

0.3

0.35

0.4

0.45

0.5

0.55

0.6

0.65

0.7

0.75

0.8

0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

B 1 2 3 B 1 2 3 B 1 2 3 B 1 2 3 B 1 2 3

40+ 50+

60+

70+

80+

Stress urinary incontinence

B 1 2 3 B 1 2 3 B 1 2 3 B 1 2 3 B 1 2 3

40+ 50+

60+

70+80+

Overactive Bladder

Figure: Progression of severity in cases of the two syndromes

Follow-up Years

Concluding Message This is the first study to explore natural history for the syndromes of SUI and OAB. It shows reasonable validity of the severity rating and differentiation between patterns for SUI and OAB. Although the two syndromes demonstrate different patterns of natural history, they share an increase in deterioration in the 60’s suggesting that this age may be a crucial time for women for both syndromes. These severity scores offer an opportunity for further modelling of change in order to explore the drivers for the natural history patterns. References

The standardisation of terminology of lower urinary tract function: report from the Standardisation Sub-committee of the International Continence Society.Neurourol Urodyn 2002; 21:167-78.

A community-based epidemiological survey of female urinary incontinence: The Norwegian EPINCONT StudyJ Clin Epidem 2000; 53:1150-7.

A detailed description, by age, of lower urinary tract symptoms in a group of community-dwelling women BJU International 2000; 82:19-24. FUNDING: Medical Research Council, UK


117 Rortveit G1, Hunskaar S1

1. University of Bergen THE ASSOCIATION BETWEEN THE AGE AT THE FIRST AND LAST DELIVERY AND URINARY INCONTINENCE Hypothesis / aims of study Deliveries, and especially the first one, have been documented as a strong risk factor for urinary incontinence in women (1). However, there is uncertainty whether the mother’s age at the first and last delivery are of importance as risk factors for urinary incontinence. Study design, materials and methods The EPINCONT study is part of the HUNT 2 survey, which was conducted in the county of Nord-Trøndelag in Norway between 1995 and 1997. All women of 20 years of age and older (n=47,313) received a mailed invitation to visit a screening station. The source population for the EPINCONT study consisted of the 34,755 community-dwelling women who attended the screening. These women were asked to complete a questionnaire at home, and 27,936 women (80 percent) answered questions related to incontinence. The resulting data set was linked to the Medical Birth Registry of Norway, in which it has been compulsory to register all births in Norway since 1967. Women who had given birth one or more times before 1967 (n=10,509), or who were nulliparous (n=4,077) were excluded. Women with any multifetal gestation (n=332), and women with any cesarean section (n=1,568) were also excluded. Women with more than five deliveries (n=33) were excluded. Women 65 years and older (n=20) were excluded, since an earlier EPINCONT substudy had found no effects of delivery in this age group. The study group then comprised 11,397 women. Women who confirmed any involuntary loss of urine, were asked about the frequency of leakage (four answer levels), the amount of leakage each time (three answer levels), the circumstance of leakage (e.g. coughing, sneezing, laughing, lifting heavy items), and whether leakage was accompanied by a sudden and strong urge to urinate. On the basis of answers about the urge to urinate and the circumstances of leakage, the incontinence was classified as stress, urge or mixed incontinence. A severity index developed and validated against a 48-hour pad weighing test by Sandvik et al. was used to characterize the degree of incontinence. Chi squared tests were performed to test statistical significance. Results Age at the first delivery was of importance for later urinary incontinence in the mother (table 1). When dichotomising age at the first delivery, we found that 23.2% were incontinent among women who delivered their first baby at the age of 25 years and under, whereas 27.7% of those 26 years and over at their first delivery were incontinent. The difference was statistically significant (P< .05). When stratifying by actual age, we found that this difference was significant in both age group 20-34 years and in age group 35-49 years. In the age group 50-64 years, however, there was no significant difference between the women who were young (25 years and under) at the first delivery as compared with the women who were older (26 years and over) at the first delivery.

Table 1. Distribution of age at the first delivery and prevalence of any incontinence in each category. Age at the first delivery (years) Number of women Prevalence of any incontinence (%) 15 years and less 20 20 16-20 3390 22.5 21-25 5367 23.6 26-30 2101 27.2 31-35 430 27.4 36-40 83 41 41 years and over 6 50 In total 11397 24.2

Increasing age at the last delivery was associated with increasing prevalences of urinary incontinence. When stratifying by actual age, there seemed to be no association between age at the last delivery and incontinence in the age group 20-34 years (Table 2). In the age group 35-49 years, the prevalence was increasing by increasing age at the last delivery, whereas this factor was not associated with incontinence in the age group 50-64 years.


Table 2. Distribution of age at the last delivery and prevalence of any incontinence in each category according to actual age.

Actual age (years) Age at the last delivery (years) Number of women Prevalence of any incontinence (%) 20-34 20 years and less 42 21.4 21-25 744 17.5 26-30 1146 21.5 31-34 275 19.6 35-49 20 years and less 115 15.7 21-25 1414 23.6 26-30 2294 24.1 31-35 1705 28.2 36-40 453 30.5 41 years and over 26 34.6 50-64 20 years and less 0 - 21-25 127 29.9 26-30 534 31.6 31-35 390 30 36-40 176 29 41 years and over 26 34.6

Interpretation of results The mother’s age at the first delivery has implications for the risk of incontinence. Mothers 25 years and under had lower prevalence than those who were 26 years and older at the first delivery. However, such a difference was not the case for women in the age group 50-64 years. This finding probably reflects that the association between deliveries and incontinence is attenuated in this age group and totally disappears in the age group 65 years and over (1,2). The mother’s age at the last delivery is not a risk factor in the age group under 35 years and in the age group 50-64 years. In the age group 35-49 years there is an association which partly may reflect the effect of the time since the last delivery, as recovering may have occurred to a larger extent the longer it is since the last delivery. This argument does, however, not seem to be of importance for the youngest age group. Concluding message Women younger than 25 years at their first delivery has a lower risk of incontinence than women who are older at their first delivery. However, this effect disappears after the age of 50. References 1. Age- and type-dependent effects of parity on urinary incontinence. The Norwegian EPINCONT study. Obstet Gynecol 2001;98:1004-10 2. Urinary incontinence after vaginal delivery or cesarean section. N Engl J Med 2003;348:900-7 FUNDING: The Norwegian Research Council 118 Fritel X1, Ringa V1, Saadoun K1, Varnoux N1, Piault S1, Bréart G1

1. Inserm U149, Villejuif, France OBSTETRICAL HISTORY AND FAECAL INCONTINENCE. A CROSS-SECTIONAL STUDY AMONG 2640 WOMEN AGED FROM 49 TO 61 YEARS Hypothesis / aims of study Faecal incontinence is a serious handicap that affects especially parous and aged women. Childbirth seems to be the principal predisposing event leading to faecal incontinence. Injury to the anal sphincter may occur during vaginal delivery [1]. Few months after delivery, anal incontinence is more frequent in case of instrumental delivery and less frequent in case of caesarean section [2]. But at menopausal age, it is unclear if caesarean section is still protective. Our purpose was to estimate the prevalence of faecal incontinence among perimenopausal women and to assess its obstetrical risk factors.


Study design, materials and methods Our population was composed of women volunteered to participate in epidemiological research. They were included in a longitudinal study between 1990 and 1996 when they were between 45 and 50 years old. This project's principal objective is to study women health during menopausal age. A questionnaire about incontinence symptoms and obstetrical history was mailed in 2000 to all women included. The prevalence of anal incontinence over the previous year was estimated from responses to the question: In the past 12 months, have you experienced involuntary loss of gas or stool? (yes or no). Severity of anal incontinence was estimated using a validated grading system [3]. Faecal incontinence was defined by involuntary loss of liquid or solid stool in the past 12 months. We tested a wide assortment of potential risk factors: age, educational level, incomes, body mass index, menopausal status, diabetes mellitus, anal surgery, hysterectomy, surgery for incontinence or pelvic organ prolapse, marital status, smoking habits, regular physical exercise, and parity. Among parous women, additional factors concerning their first delivery were tested: age, birth weight, labor longer than 12 hours, active second stage longer than 30 minutes, mode of delivery, episiotomy, urine leakage during pregnancy or first postpartum week, and third-degree perineal tear at 1st or further deliveries. We compared women with faecal incontinence versus others and conducted a multivariate analysis with stepwise logistic regression. We constructed a logistic regression model for the entire population and a second model for parous women only. The GAZEL cohort scientific committee and the French committee for health research data approved this study, which received no external funding. Results Of 3114 questionnaires sent out, 2640 (85%) were returned. Prevalence of anal incontinence in the past 12 months was 38.5% (1016), 28.6% (755) experienced gas incontinence and 9.5% (250) faecal incontinence. Risk factors associated with faecal incontinence were body mass index, anal surgery, urinary incontinence surgery, higher education, low incomes, prolonged active second stage and urinary leakage during first pregnancy or post-partum (Table). Table. Bivariate and multivariate analyses among the whole population (Model I) or among parous women only (Model II). No significant variables (age, menopausal status, smoking, physical exercise, diabetes, hysterectomy, pelvic organ prolapse surgery, marital status) not shown except parity, mode of delivery and 3rd degree perineal tear. Variables were “excluded” of multivariate analysis when they were not significant. Variables concerning the first delivery were “not introduced” in Model I.

Variables Faecal Bivariate Multivariate Incontinence

(%) OR (95% CI)

Model I OR (95% CI)

Model II OR (95% CI)

Body mass index (kg/m²)

< 25 25–30 > 30

8.1 11.2 13.6

1 1.4 (1.1-1.9) 1.7 (1.2-2.6)

1 1.4 (1.1-2.0) 1.6 (1.0-2.5)

1 1.4 (1.0-2.0) 1.4 (0.8-2.2)

Urinary incontinence surgery

No Yes

9.0 26.8

1 3.7 (2.1-6.4)

1 3.8 (2.2-6.7)

1 3.8 (2.1-6.8)

Anal surgery No Yes

9.2 15.7

1 1.9 (1.1-3.1)

1 1.9 (1.1-3.1)

1 1.9 (1.1-3.3)

Parity 0 1 2 3+

11.3 9.0 9.0 10.4

1.3 (0.8-1.9) 1 1.0 (0.7-1.3) 1.2 (0.8-1.9)

excluded excluded

High school diploma No Yes

8.8 12.0

1 1.4 (1.0-1.9)

1 1.5 (1.1-2.1)

1 1.6 (1.1-2.3)

Monthly income < 1600€ 1600-2592€ ≥ 2592€

12.5 9.7 7.4

1 0.7 (0.5-1.0) 0.6 (0.4-0.8)

1 0.7 (0.5-1.0) 0.5 (0.4-0.7)

1 0.7 (0.5-1.0) 0.5 (0.3-0.8)

Mode of 1st delivery Vaginal Instrumental Caesarean

9.3 9.9 8.0

1 1.1 (0.7-1.6) 0.9 (0.5-1.5)

not introduced excluded


Active second stage at 1st delivery

≤ 30 min > 30 min

8.1 11.8

1 1.5 (1.1-2.0)

not introduced 1 1.4 (1.1-2.0)

Episiotomy at 1st delivery

No Yes

8.1 10.2

1 1.3 (1.0-1.8)


1st pregnancy urinary leakage

No Yes

8.3 20.7

1 2.9 (1.9-4.6)


1st postpartum urinary leakage

No Yes

8.5 20.4

1 2.7 (1.6-4.4)


3rd degree perineal tear No Yes

9.2 11.4

1 1.3 (0.8-2.0)


Interpretation of results In our population faecal incontinence prevalence is similar among nulliparous and parous women. It is also similar among women delivered spontaneously, instrumentally or by caesarean section. Concluding message A caesarean section for first delivery does not seem to protect women from faecal incontinence when they reach menopausal age. References 1.Anal-sphincter disruption during vaginal delivery. N Engl J Med 1993;329:1905 2.Obstetric practice and faecal incontinence three month after delivery. BJOG 2001;108:678 3.New grading and scoring for anal incontinence, evaluation of 335 patients. Dis Colon Rectum 1992;35:482 119 Hannestad Y S1, Hunskaar S2

1. Department of Obstetrics and Gynecology, Haukeland University Hospital, Bergen, Norway, 2. Department of Public Health and Primary Health Care, University of Bergen, Norway THE ASSOCIATION BETWEEN CHRONIC RESPIRATORY SYMPTOMS AND URINARY INCONTINENCE IN WOMEN Hypothesis / aims of study It is well known that stress incontinence may occur in connection with coughing. Few studies have, however, investigated the burden of disease of incontinence among those who suffer from respiratory diseases with frequent coughing as part of the symptoms. The aim of this study was to evaluate whether women suffering from chronic respiratory symptoms were at higher risk for being incontinent compared to other women. Study design, materials and methods The EPINCONT study is part of a large survey performed in a county in Norway. 27936 women completed the incontinence part of the questionnaire. For the 6876 incontinent women (24,6%), 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 three different subtypes; stress, urge and mixed incontinence. The survey included questions about socioeconomic factors, lifestyle factors and several medical conditions. Three questions addressed respiratory symptoms: Do you have periodically daily coughing (yes/no)? Have you experienced wheezing or dyspnoea during the last 12 months (yes/no)? Do you have or have you previously had asthma (yes/no)? We combined the three variables into one scale with 4 categories corresponding to 0,1, 2 or 3 confirming answers to the questions. We considered these symptoms to be closely connected and regard the scale as an expression of severity of respiratory disease. The participants were also asked whether they used asthma medications. Proportions were used to describe the frequency of urinary incontinence symptoms in the groups. Logistic regression analyses were used to adjust for confounding and evaluate the effect of the variables under study. Because of the close relation between the three respiratory variables they were not evaluated as independent risk factors,


only the combined symptom scale was used in the multivariable analyses. In all logistic regression analyses, women with no incontinence served as the reference group. Results Of the participants, 14% reported having periodically daily coughing, 12% wheezing or dyspnoea during the last 12 months and 8% current or previous asthma. The proportion of women with 1, 2, or 3 respiratory symptoms was 3%, 6% and 14%, respectively. The prevalence of incontinence in the different groups is displayed in table 1. The prevalence of any incontinence, severe symptoms and stress and mixed incontinence was higher among women with any of the studied respiratory symptoms compared to women who did not report any respiratory symptoms. The prevalence was increasing with increasing number of symptoms. The prevalence of urge incontinence did not differ between women with or without respiratory symptoms. The results of the multivariable analyses (Table 2) showed that after adjustment for important confounders the association between number of respiratory symptoms and incontinence remained strong.

Results of multivariable logistic regression analyses, adjusted for age, body mass index, parity, smoking and use of asthma medications. Results are given in odds ratios (OR) with 95% confidence intervals (95% CI).

Table 1 Symptom Any UI (%) Severe UI

(%) Stress UI

(%) Urge UI

(%) Mixed UI

(%) Periodically daily coughing No 23 5 11 3 8 Yes 36 11 18 3 14 Wheezing or dyspnoea during the last 12 months

No

23

5

12

3

8

Yes 37 12 17 3 16 Current or previous asthma No 24 5 12 3 8 Yes 33 10 17 3 12 Number of symptoms 0 22 5 11 3 7 1 30 8 15 3 12 2 35 11 16 3 15 3 44 16 23 3 18

Interpretation of results

Table 2 Any UI Severe UI Stress UI Mixed UI OR (95% CI) OR (95% CI) OR (95% CI) OR (95% CI) No.of respiratory symptoms 0 1 1 1 1 1 1.6 (1.5-1.7) 1.9 (1.6-2.2) 1.6 (1.4-1.8) 1.9 (1.7-2.1) 2 2.1 (1.8-2.3) 2.8 (2.3-3.4) 1.9 (1.6-2.2) 2.7 (2.3-3.3) 3 3.3 (2.8-4.1) 5.6 (4.1-7.7) 3.3 (2.6-4.2) 4.7 (3.6-6.2)

Chronic respiratory symptoms and conditions like coughing, wheezing, dyspnoea and asthma are associated with an increased occurrence of urinary incontinence. Women with respiratory symptoms have more severe symptoms and are more likely to have stress leakage than other women. Concluding message Chronic respiratory symptoms seem to be independent risk factors for the development of urinary incontinence. Clinicians meeting women suffering from chronic respiratory symptoms should be aware that these women may be at higher risk for urinary incontinence. 120 Wagg A1, Mian S2, Potter J2

1. University College London Hospitals, 2. Royal college of Physicians of London QUALITY INDICATORS AND STANDARDS OF CONTINENCE CARE FOR OLDER PEOPLE IN ENGLAND Urinary and faecal incontinence occur in approximately 20% - 30% of older. People Both are the cause of great individual distress particularly to the sufferer but also to carers. The Department of Health report, Good Practice in Continence Services (2000) highlighted the need for proper assessment and management of the problem, the wide geographical variation in access to services and called for regular audit of services. In addition, the National Service Framework for Older People (2002) has set the requirement for service


providers to establish integrated continence services for older people by April 2004 Despite continence being recognised as a problem for many older individuals, there has been only limited action with a view to achieving this and provision of services remains extremely variable.

Hypothesis / aims of study To pilot clinical indicators for monitoring the quality of care in older people with urinary and faecal incontinence in primary care, hospital and long term care settings, with a view to a national audit. The objectives of this study were to: • Develop and test an audit package to assess quality of continence care for older people in line with

national guidelines • Assess the utility of the audit package across primary, secondary and institutional care. • Test the inter-rater reliability of the audit package. • Assess the time required to complete the audit. • Demonstrate variation in standards of care relating to the management of older people with continence

problems. Study design, materials and methods The audit package for this project was developed using existing national guidelines, based upon evidence where this was available. Expert consensus workshops were held to formulate quality standards where no research evidence was available. These guidelines were supplemented by a wider ranging Delphi process consisting of 100 experts in the continence field from the UK. The audit tool included indicators of: • Appropriate structures for care including standards relating to personnel, facilities, training programmes

and quality maintenance. • Processes for high quality care including specific requirements for assessment at all entry levels to the

system, investigation and treatment. • Recommended clinically relevant outcome measures, including those generated by service users, in a

wide range of clinical settings. • Clinically relevant measures of the impact of the problem on formal or informal carers.

and measures of: • Outcome indicators of value for quality maintenance by services. • Case mix, including cognitive and functional status, to allow comparison between sites and settings of

care. 15 sites in each of primary care, secondary care and the care home settings were recruited for the pilot study. Each site was required to return, in addition to organisational and outcome pro formas, 20 returns for consecutive patients with urinary incontinence and 10 for consecutive patients with faecal or double incontinence. All sites were asked to collect data on older people aged 65 and over. Analyses were performed within the CEEU using SPSS v11.5. Binley’s Directory of NHS Management was used to compile a list of English hospitals and primary care trusts which were then selected randomly and invited to participate in the audit. Care homes were randomly selected from a list of all care homes belonging to four major providers of care in England. Recruitment continued until the required number had agreed to participate. Results The audit took place over September – December 2003. 10 primary care, 13 secondary care and 11 care homes took part and returned data on organisation and process of care. The audit tool was shown to be reliable on an inter-rater study. The median kappa for the bowel and bladder questionnaires was 0.7 showing good agreement between raters. Generally, auditors found information easy to gather with the individual patient data proving most difficult (Table 1).

Table 1. How easy was it to collect the data items in the Outcome questionnaires Healthcare Setting Very easy

(1) Quite easy (2)

Neither easy or difficult (3)

Quite difficult (4)

Very difficult (5)

Primary Care 1 2 3 2 - Secondary Care - 4 3 2 - Care Homes - 4 3 - 1

8 general practices and 10 care homes had a written policy for the management of incontinence whilst only 2 hospitals had one. Integrated care pathways for patients with incontinence existed in 7 general practices, in one hospital and in none of the care homes. All care homes used care plans, as did half the general practices and hospitals. Treatment based algorithms were used rarely. 6 general practices, 10 hospitals and 10 care


homes had a screening question relating to bladder and bowel care as part of their initial assessment. A written protocol for providing a basic assessment of incontinence problems existed for 8 general practices and 10 care homes but for only 5 hospitals. Standardised measures for recording functional ability and mental state were rarely used in any care setting. A clinically defined measure of severity of symptoms was used in nearly two-thirds of general practices and one-third of hospitals and care homes. Most sites had practitioners who were able to take a continence history, initiate a frequency volume chart, perform a rectal examination and perform a urinalysis. In only 6 of the care homes were there trained staff able to perform rectal examinations. Interpretation of results

• Access to integrated continence services, as defined by “Good Practice in Continence Services” across all 3 health care settings is inadequate.

• 85% of hospitals had no written policy for continence care. • 60% of hospitals have no written protocol for providing a basic assessment of people with bladder or

bowel problems. • Regular audit of continence services occurs in less than half of the services surveyed. but nearly all

settings have access to a local continence specialist. • All settings appear confident that assessment and management occur in conditions in which privacy

and dignity are maintained. • Overall, the organisation of care appears to be better in GP practices and care homes than in

hospitals. • Overall, the audit took a median time of 18 hours to complete. • The audit performed well following reliability testing with an overall kappa in excess of of 0.7 for most

parts • Of the three health care settings, recruitment proved most difficult in the care home sector. Although

PCTs were keen to take part in the pilot, it took a considerable amount of time to identify a GP practice to undertake the audit.

Concluding message This audit has been successful identifying meaningful quality standards for continence care for older people and has demonstrated that an audit of these indicators can be used across a range of healthcare settings. The audit has resulted in findings that are worthy of further exploration and are likely to reinforce current understanding of the provision of care for older people with continence services in line with national guidelines. There is a clear case for extending this audit to a wider population. It is the first audit of its kind to take place across the health care economy and promises to deliver the requirements of the National Service Framework for Older People in terms of quality of care assurance. References

1. Royal College of Physicians. Incontinence: causes, management and provision of services. The Royal College of Physicians, London. 1995

2. Epidemiology and natural history of urinary incontinence in women.Urology. 2003 Oct;62(4 Suppl 1):16-23 3. Department of Health. Good practice in continence services. 2000. HMSO London

121 Yalcin I1, Patrick D2, Summers K 3, Kinchen K1, Bump R1

1. Lilly Research Laboratories, Indianapolis, IN, USA, 2. University of Washington, Seattle, WA, USA, 3. Purdue University, West Lafayette, IN, USA THE MINIMUM CLINICALLY IMPORTANT DIFFERENCE IN INCONTINENCE QUALITY OF LIFE QUESTIONNAIRE (I-QOL) TOTAL AND SUBSCALE SCORES IN WOMEN WITH STRESS URINARY INCONTINENCE (SUI) Hypothesis / aims of study Health related quality-of-life instruments translate a patient’s evaluation of the impact of a disease on daily life, for example on physical and social functioning, into a score that represents a continuous variable. When using this score to quantify improvements in a disease state with treatment, it is important to evaluate both the


statistical significance and the clinical relevance of an observed improvement. The aim of this study was to set two important clinical relevance reference points for the I-QOL questionnaire total and subscale scores in women with SUI: the within-treatment minimal clinically important difference (MCID) and the between-treatment MCID. The within-treatment MCID is defined as the I-QOL score increase with treatment at which patients first recognize that they are improved. For a treatment effect to be relevant, it should exceed the within-treatment MCID. The between-treatment MCID is the difference between the I-QOL score increase at which patients first perceive that they are improved and the increase at which they perceive they are unchanged. For one treatment’s effect to be considered relevantly different from another treatment’s effect, the difference in effects should exceed this between-treatment MCID threshold. Study design, materials and methods The analysis included 1133 US women with predominant SUI enrolled in two randomized, placebo-controlled studies [1,2]. Subjects were randomized to receive placebo (n=425) or one of three doses of duloxetine (n=708) for 12 weeks. Real-time urinary diaries were completed along with two validated patient-reported outcome instruments: the Patient Global Impression of Improvement scale (PGI-I – with seven ratings, see table 1 ) [3] and the I-QOL [4,5] questionnaire. The I-QOL yields a total and three subscale scores [4]. The within and between-treatment MCIDs were obtained by anchoring the I-QOL scores to the PGI-I rating, regardless of treatment assignment. The within-treatment MCID was derived as the mean I-QOL score for the group of women that rated their improvement with treatment as “a little better” on their last PGI-I. The between-treatment MCID was derived as the difference in mean I-QOL scores between the group of women that recorded a “no change” rating and the group that recorded “a little better” rating on their last visit PGI-I. Placebo and duloxetine 80 mg/day treatment differences in I-QOL scores were analyzed for statistical significance using an ANCOVA model. The number of patients needed to treat in order to gain one additional responder with duloxetine compared with placebo was calculated using the ratio 1÷(p2-p1) where p1 and p2 are the proportions of subjects who exceeded the within-treatment MCID in placebo and duloxetine groups, respectively [6]. Results Table 1 presents the I-QOL score data by PGI-I category. The within and between-treatment MCIDs for the total I-QOL score are 6.3 and 2.5, respectively. The total and subscale scores have almost identical MCIDs. Treatment with duloxetine 80 mg significantly improved I-QOL total and all subscale scores compared with placebo (Table 2). In all instances the duloxetine-placebo treatment differences exceeded the between-treatment MCIDs (4.1 for total and 3.6 to 4.5 for subscale) and duloxetine treatment exceeded the within-treatment MCIDs (10.5 for total and 9.4 to 12.1 for subscale). The number of patients needed to treat (NNT) to gain an additional I-QOL responder was 6.8, which compares favorably with NNT values reported in the literature for other treatments.

Table 1. Changes in I-QOL total and subscale scores from baseline to endpoint by PGI-I categories at endpoint Mean changes

PGI-I Category n I-QOL Total Avoidance Psychosocial Embarrassment

Very Much Better 134 19.1 20.8 14.2 25.3 Much Better 230 13.2 14.0 11.3 15.5 A Little Better 277 6.3 6.7 5.6 6.8 No Change 389 3.8 4.2 3.3 4.2 A Little Worse 47 -0.1 0.1 -0.8 1.0 Much Worse 12 -5.9 -5.8 -4.9 -7.9 Very Much Worse 2 -13.1 0 -22.2 -17.5 Within-treatment MCID 6.3 6.7 5.6 6.8 Between-treatment MCID 2.5 2.5 2.3 2.6

Table 2. I-QOL results with treatment

Placebo (n = 425) Duloxetine (n = 433) Baseline Change Baseline Change mean (sd) mean (sd) mean (sd) mean (sd) p-value I-QOL Total Score 66.6 (17.9) 6.4 (12.6) 65.4 (19.6) 10.5 (14.0) <.001 Avoidance 65.8 (18.7) 7.2 (13.9) 64.5 (19.8) 10.8 (15.0) .001 Psychosocial 75.7 (18.8) 4.9 (12.9) 74.5 (21.1) 9.4 (14.8) <.001 Embarrassment 51.6 (23.3) 8.1 (17.6) 50.5 (24.4) 12.1 (18.4) .003


Interpretation of results Treatment population differences in I-QOL scores should be greater than the between-treatment MCIDs for statistically significant differences to be considered clinically meaningful. Our findings suggest that treatment differences for I-QOL scores between duloxetine and placebo and increases in I-QOL scores from baseline with duloxetine exceed the between and within-treatment MCID, respectively. Concluding message Based on the data in this study, 2.5 points could be considered a reasonable guide for the I-QOL total score between-treatment MCID and 6.3 points for the within-treatment MCID. References 1. Am J Obstet Gynecol 2002;187:40-48. 2. J Urol 2003; 170:1259-1263. 3. Am J Obstet Gynecol 2003;189:98-101. 4. Urology 47:67-72. 5. Urology 53:71-76. 6. Statist. Med. 2001;20:893-906 FUNDING: Lilly Research Laboratories 122 Karantanis E1, Miller T1, Moore K1

1. St George Hospital THE 24-HOUR PAD TEST: PAD COMPOSITION AFFECTS ACCURACY Hypothesis / aims of study Although the 24-hour pad test has become a widely used outcome measure, the type of pad used for the test is not always stated. Continence pads vary enormously in overall dimensions, thickness, composition and amount of water-absorbing superabsorber pulp therein. Such variation in pad characteristics could particularly influence the results of studies in normal women, in whom absorption of body secretions while exposed to the warm perineum could have a large effect. Previous studies of continent women indicated normal values of 2.6-7.0g but a very recent study revealed a “dry” pad weight of only 0.3g per 24 hours. The type of pad (and number of pads worn on the perineum per 24 hours) were not stated by early authors. We hypothesise that each pad may vary in its absorption of perineal fluids and evaporation of such fluids over time. Therefore we tested a wide range of pads, with variable amounts of fluid applied to measure absorption and evaporation over varying timeframes at 37º Celsius using a humidified incubator as a substitute for the perineal environment. In doing so, we sought to identify pad-types which faithfully maintained the amounts of fluid originally applied, as these pads would be the most accurate measures of leakage. Study design, materials and methods The types of pads used are in the following table.

Pad Type Average dry weight

Superabsorber Pulp (g)

Dimensions (mm) Total capacity (mL)

Working capacity (mL)

Carefree Pantyliner* 2.4 0 140 x 40 - - Tena Active Long 3.6 1.5 175 x 70 45 25 Tena Normal 17.6 14 273 x 143 360 215 TenaComfortMiniExtra** 24.7 16 340 x 160 890 534

Firstly, the equivalent evaporation characteristics of urine and normal saline (N/S) (0.9% w/w) were tested by instilling three of each of the four pad types with 10ml of Normal Saline (0.9% w/w) and urine, placing them in room air, and weighing them after 4 and 8 hours. All weights were measured using an accurate beam balance (MFD by A&D co. Ltd. Korea) accurate to 0.1g. Next, to test for absorption of atmospheric moisture, 10 of each type of pad were placed dry in an incubator set at 37 degrees Celsius, at a CO2 of 5%, humidified with a 30 x 30cm tray containing 1 Litre of distilled water. These pads were weighed at 0, 4 and 8 hours.


Finally, to test evaporation from a wet pad over time, 10 of each of the four pads (n=40) were instilled with 2.5, 5 and 10ml of warmed N/S (total n=120) and weighed at 0, 4 and 8 hours. The larger pads were also instilled with 20 and 50 ml N/S (closer to their working capacity; additional n=20). Results Urine and Normal Saline evaporation was identical. After exposure of dry pads to a humidified incubator, some pads (Carefree pantyliner and Tena Normal) lost a small amount of weight (0.1-0.2 mls), while others (Tena Active Long, and Comfort Mini Extra) actually gained weight (0.2 mls) The evaporation of fluid instilled was much greater at 8 hours compared to 4 hours. The small pads (Carefree and Tena Active) tended to lose almost all their fluid (60-83%) after 8 hours in the incubator, especially with 2.5 and 5mls instillation. However, larger pads (Tena Normal and Tena Comfort Mini Extra) actually gained weight (between 2 and 44%) over time when instilled with these small volumes. When instilled with larger fluid (i.e. 20-50mls) volumes, the larger pads were slow to evaporate, losing only between 5 and 21% of the volume instilled. Interpretation of results Using a humidified incubator as a substitute for the warm humid environment of the perineum, this study is the first to show that differing pad types vary considerably with regard to fluid evaporation and absorption. This can be minimized by decreasing the amount of time of each pad sits on the perineum (to 4 hours during a 24-hour pad test). Thinner Carefree and Tena Active pads should NOT be used for the 24-hour pad test, even for mild leakage, because these pads allow substantial evaporation of fluid on the pad, and may lead to falsely dry results. This finding may explain the low reference ranges (0.3g) of the more recent study of normal subjects[3], as thin Carefree pads were used for approximately 8 hours. Concluding message Accurate measures of mild leakage or post-treatment cure should be determined with Tena Normal or Tena Comfort mini extra pads (or others with similar composition), as these do not allow evaporation of low fluid volumes, but are capable of holding heavier water loss with minimal evaporation. In future the ICS should stipulate that the exact type of pad used for any pad test should be precisely recorded in all publications 123 Schraffordt S1, Bisseling T2, Heintz P3, Vervest H 21. Meander Medical Centre, 2. St. Elisabeth Hospital Tilburg, 3. University Medical Centre Utrecht ARE URODYNAMIC INVESTIGATIONS A GOOD PROGNOSTIC TOOL FOR THE OUTCOME OF TVT? Hypothesis / aims of study Urodynamic investigations are performed before almost all surgical procedures for stress urinary incontinence (SUI). As a result of the urodynamics surgery may not be the first therapeutical option. This study was performed to investigate whether the use of preoperative urodynamics lead to a better postoperative result. Study design A multi center prospective cohort study of 809 patients undergoing a TVT procedure. The current follow-up is two years. Materials and methods Between March 2000 and September 2001, patients with an indication for the TVT procedure were asked to participate in this study. The procedures took place in 41 different hospitals in which 54 gynecologists and urologists performed the TVT procedure. Among the 41 hospitals there were 3 university hospitals, 25 teaching hospitals and 13 local hospitals. All participating gynecologists and urologists were qualified to perform vaginal surgery and had a short training in performing TVT’s by an experienced surgeon. Inclusion criteria were stress urinary incontinence with an indication for surgery. Exclusion criteria were: recurrent and difficult to treat urinary tract infections, significant symptoms of urge urinary incontinence, a history of or detrusor over activity at cystometry, post voiding bladder retention (>150 ml.), bladder capacity less than 200ml or a physical/mental impairment. The TVT was performed as described by Ulmsten (1). The operation


was carried out under local anesthesia using 0.25% prilocaine with adrenalin and sedation, spinal analgesia or general anesthesia. Preoperative urodynamical investigations were performed according to the ICS standards. A standardized history, physical examination and urine culture was performed preoperative, 12 and 24 months. The outcome of the TVT’s was measured with a disease specific HRQOL questionnaire the Urogenital Distress Inventory (UDI). Uebersax et al. (2) validated a short form for this questionnaire (UDI-6). These questionnaires were translated and validated in the Dutch language by van der Vaart (3). Patients received the postal questionnaires: preoperative, 12 and 24 months after surgery. As outcome variables the subscales stress incontinence, irritative and obstruction of the UDI were taken. The subscale stress comprises two questions: Do you experience, and if so, how much are you bothered by: 1 leakage related to activity, coughing, or sneezing and 2 small amounts of leakage (drops). The subscale for irritative comprises the questions: Do you experience, and if so, how much are you bothered by: 1 frequent urination, 2 leakage related to feeling of urgency. The subscale for obstructive/discomfort comprises the questions: Do you experience, and if so, how much are you bothered by: 1 difficulty emptying bladder, 2 pain or discomfort in lower abdominal or genital area. The answers give points on a 0-100 scale where 100 means the most bothersome and 0 no symptoms at all. Results On 809 women a TVT was performed. In 703 women preoperative urodynamics were performed. In 93 cases detrusor over activity was recognized and these patients were excluded from this analysis. In 106 no urodynamical investigations were performed. One case from this group was excluded because no data were received. After two years the follow-up was 74%. The results are shown in Table 1. Interpretation of results The enormous decline on the subscale stress indicates the success of the TVT for stress urinary incontinence. There is no difference in the final results for SUI whether urodynamic investigations were performed or not. When no urodynamics are performed before surgery for SUI it is believed that more obstruction post operative and urge incontinence will occur. This because an a contractile detrusor, detrusor under activity or over activity will be diagnosed before surgery is performed. We did not observe more irritative or obstructive symptoms in the group were no urodynamics were performed.

Urodynamics performed No Urodynamics P value (N = 610) (N = 105)

Age 51.3 (SD 9.8) 50.8 (SD 12.0) 0.67 Parity 2.4 (SD 1.3) 2.5 (SD 1.0) 0.55 Pre-operative Irritative 65.6 70.7 0.09 Stress 76.4 75.4 0.67 Obstructive 32.0 39.3 0.03* 1 year post-operative Irritative 28.4 30.3 0.55 Stress 13.8 14.4 0.83 Obstructive 22.4 25.8 0.25 2 years post-operative Irritative 29.7 33.8 0.20 Stress 16.0 15.8 0.94 Obstructive 24.2 22.0 0.45 Student’s t- test Table 1 * Significant P-value < 0.05 The numbers are mean scores on the UDI subscale. A high score means more bother. Concluding message Urodynamical investigations are not a good prognostic tool for the outcome of TVT. Urodynamic investigation is not superior to preoperative physical examination and history taking. References

1 Ulmsten U, Henriksson L, Johnson P, Varhos G. An ambulatory surgical procedure under local anesthesia for the treatment of female urinary incontinence. Int Urogynecol J 1996;7:81-86.

2 Uebersax JS, Wyman JF, Shumaker SA, McClish DK, Fantl JA, and the Continence Program for Women Research Group. Short form to asses life quality and symptom distress for urinary incontinence in women: the incontinence impact questionnaire and the urogenital distress inventory. Neuro Urodyn 1995;14:131-139.

3 Vaart van der CH, Leeuw de 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. Neuro Urodyn 2003;22:97-104.


124 Tibaek S1, Gard G2, Jensen R3

1. Dept of Rehabilitation, Copenhagen University Hospital, Denmark, 2. Dept of Physiotherapy, Lund University, Sweden, 3. Dept of Neurology, Copenhagen University Hospital, Denmark PELVIC FLOOR MUSCLE TRAINING ARE EFFECTIVE IN WOMEN WITH URINARY INCONTINENCE AFTER STROKE Hypothesis / aims of study The prevalence of urinary incontinence after stroke is very high: 32-79 % at admission to hospital, 25-28 % at discharge from hospital and 12-19 % six months after the stroke. The incidence of stroke in Denmark is 2 per 1 000 inhabitants corresponding to 10 000 new patients with stroke per year. The aim of this study was to evaluate the effect of Pelvic Floor Muscle Treatment (PFMT) in women with urinary incontinence after ischemic stroke. Study design, materials and methods Design: A prospective, single-blinded, parallel group design, where subjects were randomised to either Treatment Group (TG) or Control Group (CG). The subjects received written and verbal information and signed an informed consent. The ethical committee for The Copenhagen County had approved the study. Materials: A total of 339 medical records of women with stroke were screened and 26 subjects were included. The inclusion criteria were: women, with first ever ischemic stroke (WHO-definition) and verified by a CT-scan, age between 40-85 years, stroke symptoms at least in one month, urinary incontinence (ICS-definition) started in close relationship to the stroke, normal cognitive functions, independent walking abilities indoors >100 meters with/without aids and independence in toilet visits. The outcome was measured by a pre-test and a post-test using four variables of pelvic floor muscle by vaginal palpation: function, strength, static endurance and dynamic endurance. Furthermore, a diary, a 24-hours pad test and two quality of life questionnaires were used. Methods: The PFMT programme consisted of: Introduction: 1 hour Group treatment: 6-8 patients in one hour/week for a 12 week period Home exercises: 1-2 times per day Vaginal palpation: 2-3 times. The subjects in CG followed the normal, standard programme of general rehabilitation without any specific treatment of urinary incontinence. Statistics: Median and quartile ranges were used. The null-hypothesis was tested by Mann Whitney U-test between groups and by Wilcoxon test within groups. The level for statistical significance was p < 0.05. Results Twenty-four subjects completed the study, twelve in TG and twelve in CG. The median age was 60 years (interquartile range 56-74) and median duration since stroke 12 months (interquartile range 2-30). The attendance rate to treatment sessions was 90 % (66-100). A significant improvement in dynamic endurance of pelvic floor muscle (p=0.028) was demonstrated in the TG compared to the CG. A significant improvement of pelvic floor muscle function (p=0.034), strength (p=0.046), static endurance (p=0.028) and dynamic endurance (p=0.020) was also demonstrated within the TG. In CG only strength improved significantly (p=0.034), whereas there were no significant changes at function, static endurance or dynamic endurance. Interpretation of results To our knowledge the present study is the first investigation of PFMT effect performed in a random sample of women with urinary incontinence after stroke. The pelvic floor muscle improved in function, strength, static endurance and dynamic endurance in TG. In the CG the muscle strength improved over time whereas the remaining parameters were unchanged, indicating a spontaneous improvement and emphasizing the need for a control group. The improvement may be caused by improved muscle awareness and learning effect to the PFM introduced at pre-test where vaginal palpation was used as measurement. Concluding message Pelvic Floor Muscle Training had a significant effect in a controlled study of women with urinary incontinence after stroke. FUNDING: The Foundation of Danish Physiotherapists Research


125 Suzuki T1, Yasuda K1, Yamanishi T2, Kitahara S1, Nakai H1, Yamashita T1, Sato R1, Suda S3, Ohkawa H3

1. Koshigaya Hospital Dokkyo University School of Medicine, 2. Dokkyo University School of Medicine, 3. Nihon Kohden A CROSS-OVER STUDY FOR EVALUATION OF FUNCTIONAL CONTINUOUS MAGNETIC STIMULATION (FCMS) IN PATIENTS WITH URINARY INCONTINENCE ON PELVIC FLOOR MUSCLE EXERCISE (PFME) Hypothesis / aims of study To evaluate therapeutic effect of functional continuous magnetic stimulation (FCMS) on urinary incontinence in cross-over manner in patients on pelvic floor muscle exercise (PFME). Study design, materials and methods A total of 61 patients complaining of urinary incontinence were instructed to practice PFME for 4 weeks before initiation of treatment and self-administered in an incontinence questionnaire and in a QoL questionnaire (International Consultation on Incontinence- Questionnaire: Short Form (ICIQ-SF)). The study included 56 patients, from whom informed consent could be obtained in written form. They had urinary incontinence once or more a week and underwent urodynamic study (UDS): 38 having urge incontinence and detrusor overactivity (DO) (urge incontinence group) and 18 having stress incontinence but not DO (stress incontinence group). The patients of the respective groups were randomly assigned either to active-sham(A-S) treatment or to sham-active (S-A) treatment. Both active treatment and sham treatment were performed once a week for 10 weeks. The study period had a 4-week wash-out interval between the two treatment schedules. The patients were instructed to practise PFME everyday in the same way as they did in the pre-treatment period. UDS was performed at the ends of active treatment and sham treatment. Patients self-administered in the (ICIQ-SF). The incontinence questionnaire consisted of 8 items including the frequency of incontinence, urinary frequency, urge incontinence, etc. Each item was graded on a 5-rank scale. Results Bladder capacity was significantly improved after the active treatment in the A-S group (p=0.0004) and in the S-A group (p=0.0358) as compared with the initial bladder capacity (Table 1). In the former group, there were 6 patients who were well improved on the active treatment and did not undergo the sham treatment and 4 patients who discontinued the sham treatment. In the latter group, there were 2 patients who were improved after the sham treatment and discontinued the study before entry in the active treatment schedule. Leak point pressure (LPP) was significantly improved on the active treatment in the A-S group (p=0.0079) and it trended to be improved on the active treatment in the S-A group (Table 2). In the A-S group, there were 5 patients who were symptomatically improved on the active treatment and discontinued the study before entry in the sham treatment schedule and 2 patients who dropped out after the active treatment. In the S-A group, there was 1 patient who was symptomatically improved on the sham treatment and discontinued the study before entry in the active treatment schedule. In the interim evaluation (after the first half of the treatment schedule), urinary incontinence was evaluated in 23 patients of the urge incontinence group including 4 patients who were symptomatically improved on the active treatment and did not undergo the sham treatment and 2 patients who were improved on the sham treatment and discontinued the study before entry in the active treatment, and in 15 patients of the stress incontinence group including 1 patient who was improved on the active treatment and discontinued the study before entry in the sham treatment and 1 patient who was improved on the sham treatment and discontinued the study before entry in the active treatment. In the interim evaluation after the first half of treatment schedule, the UDS parameters were remarkably improved in the A-S group, but the improvement rate of incontinence was not remarkable. It trended to be greater in the A-S group and in the S-A group at the completion of the whole treatment than at the end of the first half of treatment.

Table 1. Changes in bladder capacity at strong desire to void (SD) (urge incontinence group)

Wilcoxon’s signed rank test (Mean±SD)(ml)

Pre-treatment Interim (10 weeks) Post-treatment

A-S treatment 210.6±102.2 n=20 257.0±110.8 n=19 p=0.0004

287.0±125.6 n=9 p=.0.0707

S-A Treatment 206.8±54.0 n=18 236.8±112.0 n=18 p=0.3010

254.4±97.1 n=16 p=0.0358


Table 2. Changes in LPP (Stress incontinence group) Pre-treatment Interim ( 10 weeks) Post-treatment

A-S treatment 104.4±29.8 n=10 131.6±22.2 n=10 p=0.0079

119±12.5 n=3 p=0.4446

S-A Treatment 99.0±30.2 n=8 110.8±26.1 n=8 p=0.5231

118.5±26.6 n=7 p=0.1657

Wilcoxon’s signed rank test (Mean±SD)(cmH2O) Table 3. Improvement rates of urinary incontinence and QoL in the urge incontinence group

Interim (n=14) Post-treatment (n=8) incontinence QoL incontinence QoL A-S treatment Improved

Not improved 57.1% 42.9%

28.6% 71.4%

62.5% 37.5%

50.0% 50.0%

n=9 n=6 S-A Treatment Improved


33.4% 66.6%

100% 0%

66.6% 33.4%

Incontinence Interim vs. Post- treatment p=0.1730 A-S treatment group vs. S-A treatment group p=0.0906 Fisher’s exact test Table 4. Improvement rates of urinary incontinence and QoL in the stress incontinence group

Interim evaluation n=7

Post-treatment n=6

incontinence QoL incontinence QoL A-S treatment

Improved Not improved

42.9% 57.1%

14.3% 85.7%

83.3% 16.7%

50.0% 50.0%

n=8 n=5 S-A Treatment Improved


25.0% 75.0%

80.0% 20.0%

40.0% 60.0%

Incontinence Interim vs. Post- treatment p=0.0687 A-S treatment group vs. S-A treatment group p=0.8865 Fisher’s exact test

Interpretation of results Therapeutic effect of FCMS was evidenced by remarkable improvement in UDS parameters (bladder capacity and leak point pressure) in the A-S group after the active treatment. The improvement rate of incontinence trended to be greater after the whole treatment period than after the first half of treatment in the A-S group and in the S-A group, suggesting that the improvement in incontinence is delayed in comparison with the improvement in UDS parameter. It seemed that, at the first 10 weeks, there were many patients who were not aware of improvement in incontinence and that the number of patients realizing symptomatic improvement increased only at the end of the whole treatment period of 24 weeks. Concluding message FCMS and PFME are effective for urinary incontinence. FCMS treatment results in remarkable improvement in UDS parameter in short term (two to three months). However, it seems that it takes five to six months or longer until the percentage of patients realizing the improvement in incontinence or in QoL clearly increases. 126 Pesce F1, Rubilotta E1, D'Amico A1, Curti P P1, Ballario R1, Novara G1, Artibani W1

1. Dept of Urology - University of Verona ADHERENCE TO THE ICS STANDARDISATION OF TERMINOLOGY OF LOWER URINARY TRACT FUNCTION IN THE ABSTRACTS OF THE 2003 ANNUAL MEETING OF THE INTERNATIONAL CONTINENCE SOCIETY Hypothesis / aims of study In January 2002 an updated version of the Standardization of Terminology of Lower Urinary Tract Function was published by the International Continence Society Standardization Committee in the official journal of the Society, Neurourology and Urodynamics1. As with the other similar reports by the Committee, the aim was to facilitate comparison of results and enable effective communication by investigators using urodynamic methods.


The aim of the present study was to assess the adherence to the ICS Standardization of Terminology of the Lower Urinary Tract Function by the International scientific community as it emerges in the abstracts of the papers presented at the 2003 International Continence Society (ICS) annual meeting. Study design, materials and methods The abstracts were submitted to the Scientific Committee by the deadline of 1st April 2003, i.e. about one year after publication of the report. After blind selection, 130 abstracts were accepted for presentation at the 33rd Meeting of ICS, held in Florence in October 2003. All the abstracts were published in the official ICS journal, Neurourology and Urodynamics which constituted the source of documents for the present review2. The accepted abstracts were grouped into the following 11 scientific sessions: Urodynamics, Basic Science, Quality of Life, Diagnostic technique, Pediatrics, LUTS, Bladder dysfunction, Treatment of incontinence, Neurourology, Pelvic Floor, Overactive bladder syndrome. All the abstracts were reviewed to check if the terminology used by the authors was adherent to the ICS Standardization. The distribution of the abstracts containing deviations from the standardized terminology among the various scientific sessions was also investigated. Results Out of the 130 abstracts reviewed, 44 (33.8%) included at least one non-standard term. Table 1 summarises the standard terms which were incorrectly reported in the 44 abstracts and their frequency.

Incorrectely reported term No. abstracts Increased daytime frequency 19/44 (43.2%) Detrusor overactivity 8/44 (18.2%) Storage symptoms 8 (18.2%) Dysfunctional voiding 6/44 (13.6%) Voiding symptoms 5/44 (11.4%) Urgency 4/44 (9.1%) Painful bladder syndrome 4/44 (9.1%) Involuntary detrusor contraction 3/44 (6.9%) Cystometric capacity 3/44 (6.9%) Overactive bladder syndrome 2/44 (4.5%) Others 6/44 (13.6%)

Table 1: standard terms incorrectly reported in the abstracts and their frequency. The distribution of the abstracts containing terms deviating from the standard terminology in the different sessions is reported in table 2.

Session No. abstracts not adherent/ No. abstracts per session

No. abstracts not adherent/ Overall not adherent abstracts

Urodynamics 3/6 (50%) 3/44 (6.9%) Basic Science 6/12 (50%) 6/44 (13.6%) Quality of Life 3/12 (25%) 3/44 (6.9%) Diagnostic techniques 3/12 (25%) 3/44 (6.9%) Pediatrics 9/16 (56.2%) 9/44 (20.4%) LUTS 2/6 (33.3%) 2/44 (4.5%) Bladder dysfunction 5/12 (41.7%) 5/44 (11.4%) Treatment of incontinence 4/16 (25%) 4/44 (9.1%) Neurourology 2/12 (16.7%) 2/44 (4.5%) Pelvic floor 4/20 (20%) 4/44 (9.1%) Overactive bladder syndrome 3/6 (50%) 3/44 (6.9%)

Table 2. distribution of the abstracts containing incorrect terms in the different sessions. Interpretation of results Adhesion to the ICS standardisation of terminology is a specific requirement in the submission of abstracts to the ICS annual meeting. This notwithstanding, after more than one year from the publication of the ICS Standardization of Terminology, a substantial number (34%) of the abstracts presented at the ICS annual meeting included at least one term which is considered incorrect or not recommended by the report. The most frequently occurring deviations included terms very commonly used in the urodynamic daily practice, such as detrusor overactivity, increased daytime frequency, storage/voiding symptoms. Above all, the sessions affected by presentations containing deviating terms to a larger extent were Basic Sciences and Pediatrics.


Concluding message These results call for the need of a larger circulation of the Report of Terminology Standardization among the International Urodynamics scientific community. References

1. The Standardisation of Terminology in Lower Urinary Tract Function. Neurourol.Urodyn 21:167-178 (2002.) 2. Proceedings of the International Continence Society, 33rd Annul Meeting; Neurol Urodyn, Vol 22, No. 5, 2003.

127 Shek K 1, Dietz H2

1. Tuen Mun Hospital, 2. Royal Prince Alfred Hospital, Sydney BIOMETRY OF THE PUBORECTALIS MUSCLE AND HIATUS BY 3D PELVIC FLOOR ULTRASOUND Hypothesis / aims of study The levator ani muscle is thought to play a significant role in the pathogenesis of incontinence and prolapse(1). Until recently, magnetic resonance was the only imaging method capable of assessing the levator in vivo(2). The advent of 3D pelvic floor ultrasound now enables us to evaluate the levator ani with much less cost to the health provider and minimal discomfort to the patient(3). While spatial resolution may be inferior, ultrasound technology allows dynamic imaging which is almost impossible using current MRI technology. This study was designed to define levator biometric indices on 3D ultrasound and to establish test- retest variability for those parameters in a group of young women recruited for a twin study of pelvic floor function. Study design, materials and methods In a prospective observational study, 52 nulligravid female volunteers between 18 and 24 years of age underwent pelvic floor imaging. 3D translabial ultrasound was performed after voiding and in the supine position, using a GE Kretz Voluson 730 system with 7-4 MHz 3D US transducers. Image acquisition took 3-5 seconds. The main transducer axis was oriented in the midsagittal plane. Volumes were acquired at rest and on Valsalva.

Figure: Levator hiatus at rest (left) and on Valsalva (right), oblique axial plane at the

level of minimal ap. hiatal distance. The following parameters were assessed: In the axial view, we measured maximum diameters of the puborectalis strap in two locations bilaterally and determined muscle area by tracing its outline. The plane of minimal ap- diameters was identified in the sagittal image; the axial plane was then utilized to determine the minimum ap and lateral diameters as well as the area of the hiatus. In the coronal plane we determined the distance between perineal skin and puborectalis strap, its diameter perpendicular to the skin, and its area at a level just anterior to the anorectal junction. Repeatability measures were obtained for all the above parameters and ranked between 0.45 and 0.82 (Intraclass Correlations), with best agreement shown for measures of the levator hiatus (0.7 for coronal hiatal diameter, 0.82 for the sagittal hiatal diameter and 0.74 for hiatus area.


Results Of 52 sets of volumes, 3 were excluded form formal analysis since the volumes were technically inadequate, leaving 49 datasets. The table shows results for measurements taken in the axial plane.

Parameter mean range Puborectalis diameter (axial plane) 0.73 cm 0.4-1.1 cm Puborectalis area (axial plane) 7.59 cm2 3.96-11.9 cm2 Levator hiatus at rest (anteroposterior) 4.5 cm 3.26-5.84 cm Levator hiatus at rest (left-right) 3.75 cm 2.76-4.8 cm Hiatal area at rest 11.25 cm2 6.34-18.06 cm2 Levator hiatus on Valsalva (anteroposterior) 4.73 cm 3.18-8.01 cm Levator hiatus on Valsalva (left-right) 4.11 cm 2.99-6.26 cm Hiatal area on Valsalva 14.05 cm2 6.67-35.01 cm2

Table: Selected biometric indices for pubococcygeus/ puborectalis muscle and levator hiatus in 49 nulligravid Caucasian women aged 18-24.

In the coronal plane, average distance from the perineal surface was 2.42 (range 1.48- 3.18) cm, average puborectalis diameters were 1.33 (0.5-2.55) cm; average area measurements were 1.33 (0.4- 2.72) cm2. There were no significant correlations between puborectalis biometric indices and levator function as quantified by cranioventral displacement of the bladder neck on pelvic floor contraction (e.g. total puborectalis area in the axial plane vs. displacement, r= 0.09, p= 0.5 and hiatus area vs. displacement, r= 0.08, p= 0.6)). However, there were statistically significant correlations between measures of pelvic organ mobility and hiatus area at rest (BND, p= 0.035, Cystocele descent, p= 0.018, uterine descent, p< 0.001 and rectal descent, p= 0.004). Hiatus area on Valsalva correlated even more strongly with descent (BND, r= .675, p< 0.001, Cystocele descent, r=-.628, p< 0.001, uterine descent r=-.656, p< 0.001), rectal descent, r= -.6, p< 0.001). Interpretation of results 3D ultrasound can be used to determine biometric indices of the puborectalis muscle, both for the muscle itself and the levator hiatus, with the latter probably being more reproducible. A wide range of measurements was obtained, with the levator hiatus on Valsalva varying from approximately 6 to 36 cm2. There were significant correlations between levator hiatus area and pelvic organ descent, and this relationship was observed for all three compartments. This is not surprising on Valsalva, and the increase in levator hiatus may be either cause or effect of pelvic organ descent. However, it is remarkable that levator area at rest seemed to predict descent on Valsalva. The wider the hiatus was at rest, the more descent of pelvic organs occurred on Valsalva. Concluding message This study provides support for the hypothesis that levator ani anatomy plays an independent role in determining pelvic organ support. This role seems to be stronger for the central and posterior compartments and relatively weaker in relation to bladder support. References ‘Female Urology and Urogynecology’, Isis Medical Media, London, 2001. 112-24. Ultrasound Obstet.Gynecol. 21 (2003): 589-95. Obstetrics & Gynecology 87.2 (1996): 277-85 128 Tahara H1, Okadome A2, Tahaka M2

1. Nishifukuoka Hospital, 2. Fukuoka University URETHRAL SPHINCTER VOLUME MEASURED WITH MRI. Hypothesis / aims of study To define the urethral sphincter volume measured with harmless magnetic resonance imaging (MRI) relevant to normal and abnormal voiding status. Study design, materials and methods 0.3-T MR images of the pelvis were obtained on healthy volunteers (5 men and 5 women) without endoluminal coil as the control study. In men, the urethral sphincter and urethra were visible as two layered disk-like structure between the apex of prostate and the corpus spongiosum on T2-weighted images (Fig.1). On the


other hands, urethral sphincter and urethra in women were recoginised as two layerd tube-like structure, as “urethral sphincter complex” on transvaginal ultrasound reported by Fowler et al.[1]. The urethral sphincter volume was measured as urethral sphincter complex with diameters and slice thickness on axial views of T2-weighted image and sumed up (Fig.2). MR images were also obtained on 10 men with prostate cancer treated by maximum androgen blockade and/or radiation therapies and 6 men after radical prostatectomy as a part of followup examinations. Results In male ( 27-35 y.o., average IPSS 1.4 points) and female ( 24-54 y.o., average IPSS 0 points, without any incontinences) volunteers, the average urethral sphincter volumes were 1.21 cm3 (0.92-1.87cm3) and 4.26 cm3 (2.95-5.22 cm3) respectively. Although we expected the aging atrophy in men, the average urethral sphincter volume increased to 1.74 cm3 (1.28-2.31 cm3) in 10 men with prostate cancer (72-81 y.o., average IPSS 16.1 points). But in men after radical prostatectomy (64-80 y.o., average IPSS 14.3 points, 3-82 months after surgery), the average urethral sphincter volume distinctly decreased to 1.02 cm3 (0.76-1.19 cm3). In the prostatectomy group, the average urethral sphincter volume was smaller in 3 men with stress and/or urgency incontinence (0.96 cm3) than in 3 men without any incontinences (1.11 cm3). And the relative rich average urethral sphincter volume (more than 1.00 cm3) was noticed on men in the long duration after the surgery (45.30 vs. 24.33 months). Any scarring and ischemic change of urethral sphincter could not be found on MR images. Interpretation of results Unexpected rich urethral sphincter volume in the elderly people might suggest the compensatory hypertrophy against the overactivity of the aging bladder. Radical prostatectomy itself decreased the volume of sphincter, but urethral sphincter might increase its volume as the time went by. But theses quantitive analyses should be needed a further investigation. Concluding message We reported the easy and harmless method for the evaluation of urethral sphincter with the relative low-resolution MRI without endoluminal coil. This method might be applicable for the young women and even for the children. In the future, we will apply this method for the evaluation of the diseases resulting from failure of sphincteric relaxation, such as the detrusor-sphincter dissynergia and Fowler’s syndrome.

References 1. Maximum urethral closure pressure and sphincter volume in women with urinary retention. J Urol 2002: 167: 1348-51.


129 Pajoncini C1, Natale F 1, Weir J1, Cervigni M1

1. San Carlo - IDI Hospital COMPARISON OF ANATOMICAL AND CLINICAL RESULTS OF THE TRANSOBURATOR TAPE TECHNIQUE (TOT) USING ULTRASOUND Hypothesis / aims of study The advantage of minimally invasive procedures in the treatment of stress urinary incontinence (SUI) is that high cure rate is combined with low perioperative morbidity. The transobturator suburethral tape is a new technique using a polypropylene tape inserted via the transobturator route. It produces tension free stabilization of the mid urethra rather than fixation of the bladder neck . The needle used to place the TOT is passed through a groin incision, the obturator membrane and around the descending ischiopubic ramus. The transobturator tape forms a subfascial hammock of support under the urethra. Our study was carried out to evaluate the morphologic aspect of the TOT and understand which anatomical changes are correlated with a successful result. Study design, materials and methods We studied 21 women who underwent a TOT procedure in our clinic for SUI. We included only pts with a single tape procedure. All the pts underwent ultrasonographic evaluation 6 months after TOT employing three techniques (endovaginal and transrectal using a 7.5 MHz biplanar probe, perineal using a convex 3.5 MHz probe), using a 2 axis system ( ), to evaluate the shape and the position of the tape, its distance from the bladder neck and from the pubic symphysis, the mobility of the proximal urethra in relation to the surgical outcome (cured, improved, failed). Results 18 pts were cured , 1 pt was improved, 1 was cured from SUI but had “de novo” urge incontinence and 1 failed. In the group of cured patients the cranial edge of the tape was situated an average of 12 mm above the symphysis on the x axis an an average of 15 mm on the y axis. During Valsalva manoeuvre it moved to 1 mm above the symphysis on the x axis and 13 mm on the y axis. The average tape movement was 10 mm and it occurred in a rotational motion compressing the tape against the symphisis. During Valsalva the bladder neck and proximal urethra were pushed against the cranial edge of the tape showing their compression and angulation over the tape. In a transverse scan, the distance of the 2 arms from the rabdosphincter was 23 mm. In 4 pts the length and arrangement of the 2 arms of the tape were asymmetrical. In the pt failed the position of the cranial edge of the tape during Valsalva manoeuvre was similar (13 mm on the x axis and 13 mm on the y axis) but the tape movement was decreased (3 mm). The bladder neck and proximal urethra do not angulate on the tape but they were quite fixed. Similar pictures were seen in the patient with "de novo" urge incontinence.

VALSALVA

Interpretation of results In the cured pts the TOT procedure seems not to alter the urethral mobility nor to elevate the bladder neck and proximal urethra. An important parameter for continence seems to be the tape mobility as the two pts with


troubles had a fixed tape and urethra. If the length and position of the 2 arms of the tape were asymmetrical it didn’t affect the result. The angle of the TOT is less acute than that of traditional pubovaginal sling procedures. Concluding message This ultrasound study demonstrates that the position of the TOT is quite similar to the natural position of the pubourethral ligament. The use of multiple ultrasound approaches gave an optimal view of the pelvic floor.

TAPE

VALSALVA

130 Suzuki K1, Yoshimura Y 1, Yamaguchi O 11. Department of Urology, Fukushima Medical University CAN FREQUENCY-VOLUME CHART PREDICT BLADDER OUTLET OBSTRUCTION IN RATS? Aims of study To diagnose bladder outlet obstruction (BOO) urodynamicaly, it is necessary to perform pressure flow study via a transurethral (or suprapubic) catheter. Since this procedure is invasive, some tentative non-invasive techniques using flow interruption and condom catheter have recently been reported. However, all those non-invasive methods require ultimately the measurements of pressure and flow. On the other hand, frequency/volume chart (FVC) is an instrument for the objective assessment of micturition patterns and a truly non-invasive method. If FVC can predict BOO, invasive urodynamics may be spared. Thus, the present study was designed to investigate experimentally whether FVC can predict BOO in rats. Study design, materials and methods 22 male six week-old SD rats weighing 203±6.3 g were used. Animals were divided into 2 groups and defined as group O (BOO, n=12) and group S (sham, n=10). Operation for BOO: On the rats of group O, a partial outflow obstruction was surgically created using sterile technique. Under anesthesia with pentobarbital, ventral portion of the proximal urethra was exposed through a midline incision. In order to create a mild obstruction, a longitudinally cutout Nelaton catheter (3 Fr. 3 mm in length) was placed loosely over the proximal urethra. A drop of quick-drying glue (Aronα A) was spilled over the catheter for fixation and the incision was closed. Sham surgeries were done on group S. Micturition studies: Micturition volume (V) and frequency (F) of all rats were evaluated for 2 consecutive days at the age of 18 weeks (12 weeks post operation). The rats were placed in metabolic cages with free access to water and food. Urine from each rat was collected in a container that rested on an electric scale located beneath each cage. The scales were connected to a central PC and the time of micturition and voided volume were recorded every ten seconds. From these recorded data, V, F and instantaneous diuretic rate(D=voided volume/the preceding micturition interval) for each micturition were derived. On the second day, in order to induce diuresis, the rats were given 5% sucrose in tap water to drink instead of water. Pressure/Flow studies (PFS): On the following day after the micturition studies in conscious


rats, PFS were done in all rats anesthetized with urethane. A 24 G catheter was inserted into the bladder dome and the catheter was connected to a pressure transducer and an infusion pump. Voided volume was measured by a mechanotransducer, which provided the data to measure flow and compute the flow rate-time curve. Urethral opening pressure (Puo), detrusor pressure at maximum flow (PdetQmax), micturition time (T), maximum flow rate (Qmax), voided volume (V.V.) and post-void residual (PVR) were evaluated. Bladder weight (BW): Upon termination of the study, the wet bladder weights were measured and corrected for body weight (mg/Kg). Statistics: All results were expressed as mean ± SE. Statistical analysis was performed by means of paired Student’s t-test and discriminant analysis. P<0.05 was accepted as statistically significant. Results Table summarizes the data of PFS and bladder weight. Fig. 1 shows the relationship between D and F of the rats of group S and group O, respectively. As is shown, high diuresis increases urinary frequency and a linear relationship between D and F is demonstrated in both two groups. The slope of regression line for group O is steeper than that of group S. A linea relation is also found between D and V in both two groups, however, the slope of regression line for group O is conversely less steeper than that of group S (Fig2). Since this differnce of F,V behaviors seen between two groups becomes obvious when D is in higher range, only F-V points of which D is above 2 ml/hr are plotted (Fig 3). The distribution of F-V points in group O is shifted to upper F and lower V area, compared to that of group S(Fig 3). Discriminant analysis demonstrates that 82 % of F-V points is successfully divided by discriminant line (F=1.40V+0.35)(Fig.3). It is also shown that both F and V are statistically differentiating parameters between group S and group O (relative probability; 99% for F and 95% for V). Interpretation of results A. The results of PFS, and significantly heavier bladder weight of group O compared to group S indicate that the rats of group O have BOO. This BOO is assumed to be mild because there is no significant increase in PVR. B. F-V characteristics show no difference between sham and BOO rats when the urinary excretion rate is low. However, when the urinary excretion is increased to higher range by sucrose, two groups demonstarates different F-V characteristics. If higher F and lower V behavior in micturition is found under the higher diuretic condition, it can be predicted with high probability that the rat has BOO. C. In rats with BOO, high urinary excretion may be compensated with increased urinary frequency, not with increased voided volume. Concluding message It is concluded that FVC can predict BOO with accuracy rate of 82% and therefore, invasive urodynamics can be spared in mildly obstructed rat with no residual.

Table (*<0.05, **<0.01) Puo

(cmH2O) PdetQmax (cmH2O)

T (sec)

Qmax (ml/sec)

V.V. (ml)

PVR (ml)

BW (mg/kg)

group S (n=10)

34.75 ± 3.62

31.55 ± 2.62

6.21 ± 0.82

44.85 ± 2.50

0.81 ± 0.06

0.04 ± 0.03

270 ± 11.3

group OI (n=12)

54.09 ± 3.37*

45.32 ± 3.13*

11.20 ± 0.06**

27.27 ± 1.51**

0.83 ± 0.05

0.06 ± 0.02

368 ± 11.2**

● and black line;group O, ○ and white line;groupS


Fig 3. Discriminant Analysis

0

1

2

3

4

5

6

7

0 0.5 1 1.5 2 2.5 3 3.5 V (ml)

F (n

o. o

f mic

turit

ions

/hr)

Group O (BOO) Group S (sham) discriminant line

131 Cavalcanti G1, Bruschini H1, Manzano G1, Giuliano L 1, Catarin M1, Nunes K1, Srougi M1, Nóbrega J A1 1. Federal University of Sao Paulo ELECTROPHYSIOLOGICAL STUDIES OF THE FEMALE PELVIC FLOOR IN STRESS URINARY INCONTINENCE: IS THE INTENSITY OF INCONTINENCE RELATED TO LOCAL NEUROLOGICAL DAMAGE? Hypothesis / aims of study Alterations of pudendal and urethral innervations have been identified in women with stress urinary incontinence (SUI) (1, 2). Alterations have not been associated with the severity of the urinary loss. Some authors suggest that neurological abnormalities in the urethra can be evidenced equally in patients with urinary leakages and in normal volunteers with equivalent age and parity (3). This study has the objective to investigate the urethral sensory threshold and urethro-anal reflex latency in patients with SUI and to verify the significance of these electrophysiological parameters as a tool for the quantification of the urethral function activity and degree of incontinence. Study design, materials and methods The study was in accordance with the Institutional Ethics Committee. A prospective study was accomplished in 60 women, being 37 with SUI (mean ± SD 56.1 ± 13.0 years old, range 31 to 78; 2.9 ± 2.0 deliveries, range 0 to 9), and 23 normal volunteers (mean ± SD 43.8 ± 11.2 years old, range 24 to 66; 1.8 ± 1.1 deliveries, range 0 to 4). These SUI patients were divided according to the severity of the urinary loss, established by the Valsalva Leak Point Pressure (VLPP), having 60 cmH2O as the cut off value. The results between the two different VLPP groups were compared to the control. Since there were differences in the ages (p<0.001) and total parity (p=0.02) among the groups, the comparison was accomplished between matched age and parity groups. The urethral sensory threshold corresponded to the smallest energy necessary for perception, in miliamperes (mA) searched by the method of limits. This test and the latency of the urethro-anal reflex, in milliseconds (ms), were accomplished by means of transurethral ring electrode stimulation (Medtronic 9021L0111) and peri-anal surface electrodes recordings. For the comparative study we used the test of Kruskal-Wallis. The significance level was 5% (< 0.05).


Results The results from comparison between groups with similar age and parity levels are discriminated in tables 1 and 2, respectively.

Table 1: Results of the urethral sensory threshold and urethro-anal reflex latency in control and SUI groups with equivalent ages. Control group SUI SUI

VLPP VLPP (> 60 cmH20) (< 60 cmH20)

Electrophysiological test

A B C

p value

3.0 ± 1.0 3.5 ± 1.8 4.7 ± 2.3 (1.6-4.4) (1.6-7.6) (2.0-9.0)

Urethral sensory threshold (mA)

(n=13) (n=16) (n=17)

0.08

55.6 ± 4.4 65.4 ± 9.4 62.5 ± 8.4 0.007 (47.2-2.7) (47.2-78.4) (53.2-78.0) a x b < 0.01

Right urethro-anal reflex latency (ms)

(n=15) (n=17) (n=18)

56.1 ± 5.9 62.0 ± 8.6 62.6 ± 7.8 0.02 (45.6-72.0) (47.2-78.4) (54.0-78.0) a x c < 0.05

Left urethro-anal reflex latency (ms)

(n=15) (n=16) (n=16)

49.5 ± 9.1 54.6 ± 16 57.1 ± 11.2 Age (years)

(38-66) (31-77) (35-78) 0.21

Table 2: Results of the urethral sensory threshold and urethro-anal reflex latency in control and SUI groups with equivalent parities.

Electrophysiological test Control group SUI SUI p Value VLPP VLPP (>60 cmH20) (< 60 cmH20) A B C Urethral sensory threshold (mA) 3.0 ± 0.9 3.5 ± 1.8 4.7 ± 2.3 0.08 (1.6-4.2) (1.6-7.6) (2.0-9.0) (n=14) (n=16) (n=17) Right urethro-anal reflex latency (ms) 53.8 ± 3.4 65.4 ± 9.4 62.5 ± 8.4 0.0003 (47.2-60.0) (47.2-78.4) (53.2-78.0) a x b < 0.001 (n=15) (n=17) (n=18) a x c < 0.01 Left urethro-anal reflex latency (ms) 55.4 ± 5.7 62.0 ± 8.6 62.6 ± 7.8 0.005 (45.6-72.0) (47.2-78.4) (54.0-78.0) a x b < 0.05 (n=15) (n=16) (n=16) a x c < 0.01 Parity (number of deliveries) 2.4 ± 0.6 3.5 ± 2.7 2.7 ± 1.2 0.43 (2-4) (0-9) (0-5)

Interpretation of results There was no difference in the average of the urethral sensory threshold among the groups, although the results suggest a tendency to higher values as the urinary incontinence becomes more serious. The urethro-anal reflex average latency was higher on both sides in the incontinent patients when compared with normal volunteers, although no differences were found between the groups with VLPP above or under than 60 cmH20. Concluding message A delay in the urethro-anal reflex latency was found in women with SUI and also a tendency to progressive increase of the urethral sensory threshold. These alterations were not correlated to age or parity. Thus, abnormalities of the urethral innervation may play a role in the cause of stress urinary incontinence. The clinical implications allowing different therapeutic approaches still have to be determined. These electrophysiological parameters were unable to identify the degree of urinary loss. References 1. Neurophysiological abnormalities in genuine female stress urinary incontinence. Br J Obstet Gynaecol 95: 705-10, 1988. 2. Sacral evoked potentials in normal women and in women with stress incontinence. Neurourol Urodyn 6: 321-4, 1987. 3. Denervation and reinnervation of the urethral sphincter in the etiology of genuine stress incontinence: an electromyographic study. Br J Obstet Gynaecol 100: 750-3, 1993. FUNDING: FAPESP


132 Catarin M1, Manzano G1, Bruschini H1, Cavalcanti G1, Juliano L1, Nunes K1, Arruda H1, Srougi M1, Nobrega J1 1. Federal Uinversity of São Paulo A METHOD FOR ANALYSIS OF PUDENDAL NERVE INTEGRITY THROUGH PENILE DORSAL NERVE STIMULATION AND INTRAURETHRAL SURFACE ELECTRODE REGISTRATION. Hypothesis / aims of study The integrity of pudendal nerves seems to be fundamental in the maintenance of post radical prostatectomy urinary continence and penile erectile function. The exact mechanism involved is still subject of discussion (1,2). Limitations for these studies are the necessity of needle punctures and lack of clinical conclusions from the results of the methods now available. Herein we describe a way to identify the integrity of these nerves by a less invasive procedure, making it more suitable for practical application. Study design, materials and methods The study was in accordance with the institutional ethics committee. From February 2003 to March 2004, 20 male patients were prospectively enrolled in this study after been considered neurologically normal. After patient's consent, the pudendo-urethral reflex was obtained through direct stimulation of the dorsal nerves in the proximal third of the penis. Registration was obtained directly in the membranous urethra at the level of the external urethral sphincter through a surface electrode, mounted in a Foley catheter, 10 F, about 2,5 cm external to the balloon. This procedure located the electrode at the level of the sphincter at the membranous urethra. The precise position of the electrode was determined by digital rectal examination. All individuals were submitted to measurements of the sensory threshold and the reflex latency time. (Fig 1). Fig.1 - Schematic representation of the pudendo-urethral reflex.

Results The pudendo-urethral reflex was recorded in all the patients studied. The analysis demonstrated that the sensory threshold ranged from 1.0 to 5.0 mA, with average and SD of 2.62 ± 1.03 mA. The reflex latency ranged from 22 to 50.8 mseg, with average and SD of 34.06 ± 7.9 mseg. (Table 1). Table 1 – Results of the pudendo-urethral sensory threshold and pudendo-urethral reflex latency.

Patients Sensory Threshold Reflex Latency 1 1 50.8 2 3.6 31.6 3 2.8 49.6 4 2 31 5 4 36.8 6 2.2 41.6 7 1.8 28 8 5 33.4 9 2.6 29.6


10 2.4 30.4 11 2.4 22 12 4.6 36.8 13 2.2 31 14 2.4 34.8 15 1.8 43.6 16 1.4 30.8 17 2.2 27.7 18 3.4 41 19 2.6 23.6 20 2 27 Mean 2.62 34.06 SD 1.03 7.90

Interpretation of results The consistency of the responses in 100% of the cases demonstrate the viability of this technical variation as a less invasive and reliable method for the analysis the pudendal urethral reflex in males. The results here obtained are in accordance with others in the literature (3). Concluding message This less invasive approach for detection of pudendal urethral reflex allows a widespread use in patients going to radical prostatectomy. Comparison of the pre and post operative results will favorably contribute to a better understanding of such innervations in maintaining urinary continence and penile erection. References

1. Sphincter electromyography in patients after radical prostatectomy and cystoprostatectomy. Brit J Urol, 69: 397, 1992. 2. Risk factors for urinary incontinence after radical prostatectomy. J Urol, 156: 1707, 1996. 3. Clinical application of sacral reflex latency. J Urol, 129: 1187, 1983.

FUNDING: FAPESP 133 Slack M1, Tracey M2, Hunsicker K2, Patel B2, Godwin A2

1. Addenbrooke Hospitals , 2. Ethicon, Inc. ASSESSMENT OF URETHRAL FUNCTION USING URETHRAL RETRO-RESISTANCE PRESSURE IN WOMEN WITH AND WITHOUT STRESS URINARY INCONTINENCE Hypothesis/Aims of the studyUrethral function has been assessed for over 75 years by a variety of methods. The clinical utility of commonly used measures of urethral function including maximal urethral closure pressure (MUCP) and leak point pressure (LPP) remains to be established. One study demonstrated that a low MUCP was associated with a poorer outcome following retropubic urethropexy [1]. The Urethral Retro-resistance Pressure (URP) is a new retrograde measurement of urethral function. URP is the pressure required to achieve and maintain an open sphincter. The aims of this study were as follows. 1) We compared the average URP value in women without SUI (asymptomatic) to the average URP value in women with SUI (symptomatic). 2) We evaluated the within-subject variation of the URP measurement at a single visit and the within-subject change in URP over time using test and retest values. 3) We explored the effect of baseline covariates on URP. 4) Using the URP values derived from populations of asymptomatic and symptomatic women, we determined the likelihood that a given URP value indicates SUI. Study design/Materials & Methods Four centres enrolled 61 women without symptoms of urinary incontinence and negative standing stress tests. Fifty-six of these women were premenopausal. In a separate study, 23 centres enrolled 79 premenopausal women with symptoms of SUI. Each centre performed three consecutive URP measurements on each subject. At two centres, 32 asymptomatic women returned in 3 to 7 days for three additional URP measurements. Each patient emptied her bladder, was positioned in a semi-lithotomy position and instructed to relax her pelvic floor. The URP was measured by placing a cone-shaped meatal plug 5mm into the external urethral meatus, creating a seal. The device infused sterile fluid at a controlled rate of 1 mL per second. The device displayed the pressure (cm H20) required to open the sphincter over a period of 20 seconds. The curve plateau


represented the pressure at which the open sphincter was maintained (Figure 1). The URP is a catheter-less procedure and avoids catheter-induced systemic artifact. Test and retest correlation analysis on the URP measurement was performed and “limits of agreement” were established using Bland-Altman approach.

Figure 1: URP curve

ResultsThe mean age of the asymptomatic group was 33 (± 9) years and the mean body mass index (BMI) was 24 (± 6). The symptomatic group had a mean age of 44 (±6) years and BMI of 27(±6). The URP values were normally distributed in both groups. The mean URP for the asymptomatic group (n=56) of 111.9±40.1 cmH2O was significantly higher than the mean URP of 76.7±26.7 cmH2O for the symptomatic group (n=79) [p<0.0001]. The mean within-subject standard deviation of URP values measured at visit 1 was 12.6±12.6 cmH2O (n=60) and at retest visit was 9.3±6.2 cmH2O (n=32). For the retest cases, the mean URP at visit 1 was 113.9±39.9 cmH2O (n= 32) and 125.5±33.9 cmH2O (n=32) at the retest visit (Wilcoxon Signed Rank Test, p=0.145). The correlation between test and retest URP values was 0.65 (90%CI 0.44-0.80). Interpretation of URP values is detailed in Table 1.

Table 1: Interpretation of URP value*

*Based on 79 women with SUI and 56 women without SUI

URP Results Interpretation P-value ≤ 46 SUI < 0.05 47 – 61 Very likely to have SUI 0.05 – 0.10 62 – 79 Likely to have SUI 0.10 – 0.20 80 – 99 Results Inconclusive 100 – 110 Unlikely to have SUI 0.10 – 0.20 111 – 120 Very unlikely to have SUI 0.05 – 0.10 ≥ 121 No SUI < 0.05

Interpretation of resultsThe URP measurement in premenopausal asymptomatic women has a normal distribution curve, good test-retest correlation, and demonstrates a distribution that is significantly different from the distribution of URP values in premenopausal women with SUI. Avoidance of a urethral catheter eliminates the possibility of catheter artifact. This, along with the finding of a normal distribution curve for URP values in both groups is consistent with URP being a physiological measure of urethral function. The URP measurement has the potential to discriminate between women with and without SUI. However, more data is needed on asymptomatic postmenopausal women in order to determine the true overlap of URP in asymptomatic and symptomatic women. Additionally, outcome studies are required to establish the role of URP in the assessment of urethral function. Concluding messageThe data suggest that URP measurement shows promise in aiding in the diagnosis of urinary incontinence and in assessing urethral function. Reference [1] The low pressure urethra as a factor in failed retropubic urethropexy. Obstet Gynecol 1987; 68: 399-402 FUNDING: Ethicon, Inc. a Johnson & Johnson Company


134 Visco A1

1. University of North Carolina, for the Pelvic Floor Disorders Network COMPARISON OF MEASUREMENTS OBTAINED WITH MICROTIP AND EXTERNAL WATER PRESSURE TRANSDUCERS Hypothesis / aims of study The aim of this study was to compare simultaneous pressure readings obtained with catheter-mounted microtip and external water pressure transducers during filling cystometry. Study design, materials and methods During multichannel urodynamic testing, two 8Fr urodynamic urinary catheters were simultaneously zeroed at the urethra and placed into the bladder. 107 women were recruited of whom 97 produced evaluable data; the primary reason for data being excluded was detrusor instability. Women were randomized to a combination of either two microtip (MM, n = 16) or two external water pressure transducer (WW, n = 18) catheters, or a combination of the two transducer types (MW, n = 63). Both transducers were connected to a multichannel urodynamic recorder so both pressure tracings could be recorded concurrently. A series of three coughs and two Valsalva manoeuvres of various strengths and at different volumes (150mL, 300mL) were then performed during the course of cystometric evaluation. Cough efforts generated pressures < 50, 50-100, and > 100cm water over baseline. Valsalva efforts generated pressures < 75 or ≥ 75cm water over baseline. The simultaneous intravesical pressure (IVP) readings generated by the two systems at baseline, and the maximum IVP readings at each event were then compared using paired t-tests and Pearson correlation coefficients. Results Data were analyzed from 97 patient volunteers. The subjects had a mean age of 54.2±13.0 years, 89% were Caucasian and 9% were African American. The differences between IVP readings from the catheter pairs were calculated. Microtip catheters showed the smallest mean differences (0-1cm H2O), while external water pressure transducers showed slightly larger mean differences (3-8cm H2O). Large mean differences were observed when comparing microtip and external water pressure transducers catheters (8-24 cm H2O pressure, all p-values <0.001 by paired t-test) (Table 1). The standard deviation of the differences were large between microtip and external water pressure transducers compared to those between catheters of the same type.

Table 1. Mean (±SD) IVP between transducers (cm H2O) Volume IVP Difference Mean (±SD) MM MW WW 300ml Valsalva 1 0 (±2) 8 (±11) -5 (±6) Valsalva 2 -1 (±2) 10 (±13) -5 (±7) Cough 1 0 (±1) 10 (±14) -3 (±5) Cough 2 -1 (±2) 17 (±19) -6 (±7) Cough 3 -1 (±4) 24 (±27) -8 (±11)

Correlation of maximum pressure readings was consistently high between microtip transducers (r = 0.99), regardless of the type of manoeuvre, or the volume of testing. Correlation between external water pressure transducers was also high across varying manoeuvre types at both testing volumes (r = 0.96-0.99). Correlations were lower between readings of microtip and external water pressure transducers (r=0.89-0.94). Within this group, correlations were lower for baseline readings and coughs compared to Valsalva manoeuvres (Table 2).

Table 2. Pearson correlation between transducers Groups MM MM* MW MW* WW WW* 150cc Baseline 0.91 - 0.71 - 0.74 - Cough 0.99 0.99 0.87 0.89 0.97 0.96 Valsalva 0.99 0.99 0.92 0.93 0.95 0.97 300cc Baseline 0.93 - 0.66 - 0.80 - Cough 0.99 0.99 0.88 0.89 0.98 0.98 Valsalva 0.99 0.99 0.92 0.94 0.94 0.97

*Adjusted for baseline pressure prior to event


Interpretation of results Small standard deviations and high correlations were seen for transducers of similar type, suggesting excellent reproducibility. While correlation between microtip and external water pressure transducers was also high, there were significant differences in the maximum pressures measured by these two systems for individual pressure events. The mean differences between microtip and external water transducers for the strongest cough efforts were large and could be clinically significant. Differences were greatest for rapid pressure changes (cough efforts) and appear to increase in proportion to the magnitude of the pressure generated. A similar effect was not seen with Valsalva manoeuvres. The large standard deviations seen suggest considerable variability in pressures recorded by each transducer, indicating that these systems are not simply interchangeable. Concluding message The differences in pressure readings between microtip and external water pressure transducers are clinically significant, particularly for cough efforts of a strength used for clinical testing; therefore, pressures obtained from these catheters should not be assumed to be directly comparable. Research studies should use a consistent catheter type and not alternate between the two when recording leak point pressures. Microtip transducers showed the smallest intracatheter variability and may provide data of higher reproducibility. FUNDING: Supported by grants from the National Institute of Child Health and Human Development (U01 HD41249, U10 HD41268, U10 HD41248, U10 HD41250, U10 HD41261, U10 HD41263, U10 HD41269, and U10 HD41267). 135 Kalivas K1, Dimitriadis G 1, Vasilakakis G1, Katsikas V1, Zougas K1, Radopoulos D1

1. 1st Urology Department,Medical school, Aristotle University of Thessaloniki THE INFLUENCE OF URODYNAMIC CATHETER ON IDIOPATHIC DETRUSOR-SPHINCTER DYSSYNERGIA (DYSFUNCTIONAL VOIDING) DIAGNOSIS IN WOMEN Hypothesis / aims of study Dysfunctional voiding(or idiopathic detrusor sphincter dyssynergia, or sphincter overactivity voiding dysfunction) is a condition in which there is a lack of coordination between the sphincter and detrusor during emptying in a patient without overt uropathy or neuropathy1,2. The aim of this study was to define whether the existence of even a small urodynamic catheter intraurethrally, creates a false positive picture of dysfunctional voiding in women. Study design, materials and methods The study group was composed of female patients referred to the laboratory of urodynamics with complaints suggestive of urine storage or voiding problems. The study was done using a multichannel urodynamic equipment (Lifetech, Houston, USA). A 6 Fr, double lumen, transurethral urodynamic catheter was used in every subject, and no videourodynamic studies were performed. Surface electrodes were placed to perineum near the labia majora trying to avoid as possible the approximation with the adductor muscles of the thigh. Any involuntary detrusor contraction was considered to be a sign of unstable bladder. The voiding was classified as dysfunctional if an increased electromyographic activity during voiding was detected. Exclusion criteria: Neurological disease diagnosis based on patient’s history, clinical or radiological tests, documented genitourinary infection or instrumentation during the last month, severe genital atrophic changes, pelvic floor prolapse >2nd degree, and traumatic catheterization. Inclusion criteria: Increased electromyographic activity during voluntary voiding, no signs of significant electrical activity before and after voiding, and the muscle electrical activity to cover more than one fifth of the total voiding curve. Statistical analysis was performed using the Student’s t-test for continuous data, and the Fischer’s exact test for categorical data. P< 0.005 was considered to be statistically significant. Data were summarized as mean +/- standard deviation, or percentage according to variables Results From a total of 63 consecutive female patients, presented in urodynamics laboratory, only 33 were eligible to be enrolled to the study. Mean age was 51+/- 13 (19 to 76 years). Details of patients’ descriptive statistics and demographics are shown in table 1. There was no statistical difference between dysfunctional voiding


without/with catheter and bladder instability, interrupted pattern of urination with catheter. Statistical significant association was found between dysfunctional voiding without catheter and interrupted pattern of urination without catheter [P=0.015, Odds ratio = 12 (95% CI 1,5-142)] Interpretation of results Our main result was that no statistical significant difference was observed between voiding function and presence of a urodynamic catheter (Table 2). In our study, due to our small sample, we didn’t take into account a specific pattern of electromyographic activity during voiding, even though we observed a tendency for various patterns3. Because according to the recent ICS terminology, dysfunctional voiding “ is characterised by an intermittent and/or fluctuating flow rate due to involuntary intermittent contractions of the peri-urethral striated muscle during voiding in neurologically normal individuals”, we tried to investigate whether there was a change of urinary flow pattern or not. The results have shown that the catheter can influence the voiding curve pattern towards an interrupted pattern. Concluding message The present study demonstrated that even though the results favour an influence of catheter existence in urethra in developing dysfunctional voiding this has no statistical basis and therefore sphincter overactivity during voiding, in the presence of a catheter, can be safely interpreted as dysfunction, having in mind that there is a small probability to be an artefact. Nevertheless the voiding pattern can be influenced by the catheter existence in patients with dysfunctional voiding.

Dysfunctional voiding with catheter

Dysfunctional voiding without catheter

Total Statistics

Age (years) N=26 51+/- 14 N=7 50+/- 10 N=33 51+/- 13 t-test N.S.* Q max with catheter (ml/s) N=26 19+/-8 N=7 15+/-5,5 N=33 18,2+/-8 t-test N.S.* Q max without catheter (ml/s) N=26 18,5+/-9 N=7 18+/-4 N=33 18,50+/-8,5 t-test N.S.* Detrusor Instability N=10 30% N=23 70% N=33 100% Fischer’s exact test N.S.* Interrupted voiding with catheter N=16 48% N=17 52% N=33 100% Fischer’s exact test N.S.* Interrupted voiding without catheter N=8 24% N=25 76% N=33 100% Fischer’s exact test P=0.015

Table 1. Descriptive Statistics of patients’ urodynamic characteristics. N denotes the sample number in each category, data are presented as mean+/- standard deviation, or percentage according to variables, * N.S.= Without statistical significance

Voiding dysfunction Non-voiding dysfunction With Catheter 15 11 26 Without Catheter 2 5 7 17 16 Total: 33 Table 2. Crosstabulation of voiding function vs catheter presence. Fisher's Exact Test

P= 0.225 (N.S.), Relative Risk= 2,02 (95 % CI = 0,6 to 6,8) References 1)Dysfunctional voiding in women. J Urol 165; 143-148, 2001 2) Dysfunctional voiding in women: which muscles are responsible? Br J Urol. 1998 Dec;82(6):814-9. 3) Flow evaluation and simultaneous external sphincter electromyography in clinical urodynamics. J Urol 125; 542, 1981 136 van Mastrigt R1, Huang Foen Chung J1

1. ErasmusMC BLADDER VOLUME SENSITIVITY OF NON-INVASIVELY OR INVASIVELY MEASURED ISOVOLUMETRIC INTRAVESICAL PRESSURE Hypothesis / aims of study Repeatedly it has been asked if the bladder volume influences the accuracy of non-invasive bladder pressure measurements. Basically these methods proceed by (repeated) interruption of voiding. Earlier we reported the bladder volume dependency of the isovolumetric pressure in 9 volunteers each voiding approximately 20 times using the condom catheter method [1]. We concluded that the bladder volume must be considered to obtain a reliable estimate of the isovolumetric bladder pressure. Presently we conduct a longitudinal study on more than 1000 subjects using this non-invasive method [2], which enables us to analyse the volume sensitivity of


this and other non-invasive or invasive methods of measuring isovolumetric intravesical pressure, and recommend cut off values for the bladder volume. Study design, materials and methods 11914 males of age 38-77 were invited to participate in the study, mainly by 25 general practitioners. A complete flowchart of the recruitment is available, a preliminary version was published earlier [2]. Although certain conditions were excluded, LUTS was not an exclusion criterion [2]. In 1021 subjects at least one succesful condom catheter measurement was done. From 986 of these also a correct 3 day voiding diary was available. A bug corrupted the volume dependence of 9 measurements, leaving 977 measurements in 977 subjects to be analysed. On average voiding was interrupted 5 times.

0 200 400 600 800 1000

Bladder volume [ml]0

50

100

150

200

Max

imum

con

dom

pre

ssur

e [c

mH

2O]

Results The maximum condom pressure was linearly interpolated to derive values at evenly spaced bladder volume values, and mean ± standard error were plotted in the top panel. The high standard errors at high bladder volumes reflect that most subjects did not void such large volumes. In the lower panel maximum condom pressure was normalised by dividing the values measured in each subject by the maximum value in that subject. The bladder volume was normalised by dividing the volume readings in each subject by the volume reading at his maximum pressure. In 381 / 977 = 39% of the subjects the highest pressure was measured at the first interruption of voiding. I.e. there was no true maximum as shown in the lower panel, the maximum pressure steadily declined from the first interruption onwards. In the other 61% of subjects the maximum pressure was read at a later interruption, so that with decreasing bladder volume the maximum condom pressure first increased and then decreased as shown in the lower panel. The table compares descriptives of the volume at which the maximum pressure was found with the voided volume (of the interrupted voiding) and the median and maximum volume registered in the voiding diaries. It also shows the Pearson) correlations of those volumes. Due to the large number of subjects, all these correlations were significant.

Variable [ml] Mean Median Standard error of the mean

Correlation with Volume at max press

Median diary volume 240 220 3 0.20 Volume at max pressure 252 236 4 - Voided volume 364 346 5 0.81 Maximum diary volume 505 475 6 0.21

Interpretation of results The majority of the 977 pressure-volume relations measured in the subjects show a distinct maximum. All of these were found at different bladder volumes. By averaging the data, as in the top panel, the maxima therefore disappear. The graph does show however, that below a bladder volume of approximately 200 ml the average pressure dramatically declined. The median of the volume at which the maximum condom pressure was found is 236 ml, indicating that for half of the subjects, the pressure started to decline at that volume. By normalising volumes to the volume at maximum pressure, as in the lower panel, the shape of the curves is exaggerated, i.e. even if there is no true maximum, which was the case in 39% of subjects, the decline with lower volumes still contributed to the shape of the maximum in the graph. The decline in the graph is reliable though, roughly linear with the bladder volume, and amounting to approximately 8% for each 10% of volume decrease. A pressure reading at 50% of the volume at the highest reading, is thus reduced to approximately 60%. The volume at maximum pressure was strongly related to the voided volume, which is artefactual, as it


cannot exceed that volume. It was significantly, but very weakly, correlated to the median and maximum of the voided volumes registered in a 3 day voiding diary. It thus seems that the volume at maximum pressure represents a different mechanism. It is suggested that the functional (=maximum) and sensory (=median) capacity derived from a voiding diary [3] represent neurological properties of the bladder, whereas the volume at maximum isovolumetric pressure represents mechanical properties. Concluding message Isovolumetric pressure readings of the bladder, either non-invasively or invasively measured, should be taken at or above the optimum bladder volume for such measurements. At volumes lower than the optimum volume the pressure decreases by approximately 8 % for each 10% of volume decrease. At bladder volumes smaller than 236 ml pressure readings in 50% of subjects are suboptimal. The bladder volume at maximum isovolumetric pressure probably represents mechanical properties of the bladder, whereas voiding diary parameters more likely represent neurological properties. References

1. Repeat noninvasive bladder pressure measurements with an external catheter. J. Urol. 162 : 474-479 (1999) 2. Applicability and reproducibility of the condom catheter method for measuring the isovolumetric bladder pressure. Urology 63 :

56-60 (2004). 3. Measurement and analysis of voided volumes using a small electronic pocket balance. Sc.J.Urol.Nephrol.30 : 257-263 (1996).

FUNDING: This study was supported by the Dutch Kidney Foundation (PC85), and the foundations 137 Valentini F1, Hermieu J2, Zimmern P3, Nelson P 4, Besson G4

1. E349 INSERM-Université Pierre et Marie Curie France, 2. Hôpital Bichat-Paris France, 3. Southwestern Medical Center-Dallas USA, 4. E349 INSERM- Paris France THE USE OF A MODELIZED ANALYSIS OF FREE UROFLOWS (FF) TO IMPROVE WATCHFUL WAITING OF PATIENTS WITH BENIGN PROSTATIC ENLARGEMENT (BPE). Hypothesis / aims of study The obstructive status of a BPE patient is characterized by the urethral obstruction and by the contractile behavior of the detrusor. One cannot obtain quantitative evaluation of these two parameters from only FF. The aims of this study are 1) to define a parameter which can be evaluated from only FF and would be able to estimate the risk of retention for BPE patients, 2) to show how a modelized analysis of FF allows to obtain the value of this parameter, 3) to discuss its physiological meaning. Study design, materials and methods The population was composed 137 BPE patients. One hundred thirteen patients were included in a pharmacological study and performed only FF; 24 patients underwent urodynamics before TURP. A total of 306 free uroflows FF and 112 pressure-flow studies (P-Fs) were usable. Seventy nine files provided special interest as they contained several urodynamic tests (10 FF and 4 P-Fs for 9 files, 5 FF for 70 files). Theoretical developments used the VBN modeling of micturition for a male patient [1]. Urethral obstruction and detrusor force were characterized respectively by two parameters: pucp is the prostatic urethra counter-pressure and k the detrusor force coefficient. From any couple of parameters (pucp, k), and for any initial bladder volume, the model allowed to compute theoretical flow rate and detrusor pressure curves. An automated version of the VBN method without manual intervention except to click on a switch “do calculation” was used to find the best fitting (quadratic error < 2%) between computed and recorded flow curves. Results Any free flow curve could be attributed to a family of “homologous voidings”. It meant that for a given flow curve, a set of detrusor pressure curves could be associated, each with a different couple (pucp, k). All the couples (pucp, k) of a given family were on a curve in the pucp, k plane. This curve was referenced by a critical point RRp (Retention Risk parameter, this name will be justified in “interpretation of results”) which was the value of pucp for k = 1 (normal detrusor). All the homologous voidings had the same residual volume (and the same maximum flow rate Qmax). RRp did not depend on the value of the initial bladder volume neither on the nervous control but (on the opposite of the maximum flow rate Qmax) only on the obstructive status of the


patient. It was an estimation of the balancing of the urethral obstruction by the detrusor. From any flow recording, the automated VBN software gave in few milliseconds the value of RRp. Comparison of the results from files including several recordings found an accuracy of +/- 3 cm H2O for the RRp value. On the figure, the left part shows how to determine the value of RRp. The right part represents the residual volume Vr versus the initial bladder volume Vi for different values of RRp; it shows how retention will occur for great values of RRp. Interpretation of results From theoretical computations, the figure above shows that RRp = 30 cm H2O implies large residual volume, RRp between 30 and 40 cm H2O retention for large initial bladder volume and RRp > 40 cm H2O retention whatever the initial volume. Looking at the studied population we saw that the patients included in the pharmacological study had a value of RRp in the range [16-31 cm H2O] mean RRp = 24 cm H2O when the pre-TURP patients had a significantly higher value of RRp: range [27-36 cm H2O], mean RRp = 32 cm H2O. Thus we saw that the value of RRp was linked to a retention risk.

Concluding message A clearly defined parameter RRp which only depends on the obstructive status of a BPE patient can be deduced from a free uroflow recording; it is more accurate than the Qmax as it does not depend on the testing circumstances. This parameter is easy to evaluate and can be related to a risk to develop retention; it can help the clinician when watchful waiting is proposed to a BPE patient. References [1] Modelized analysis of pressure-flow studies of patients with lower urinary tract symptoms due to benign prostatic enlargement. Neurourol Urodyn 2003. 22: 45-53. 138 Lovatsis D1, Drutz H1, Petropoulos S2

1. University of Toronto, 2. University of Western Ontario ANALYSIS OF THE COUGH STRESS TEST AND MULTICHANNEL URODYNAMICS FOR THE DIAGNOSIS OF STRESS URINARY INCONTINENCE IN WOMEN Hypothesis / aims of study The aim of this study was to determine the predictive value of the cough stress test (CST) for the diagnosis of stress urinary incontinence (SUI) in women during the evaluation of lower urinary tract symptoms in three scenarios: (i) initial evaluation upon consultation, in the absence of significant pelvic organ prolapse (POP), (ii) initial evaluation upon consultation, in the presence of significant POP, and (iii) after continence surgery. Study design, materials and methods Retrospective chart review of 297 consecutive female patients who were evaluated at a tertiary Urogynecology unit for pelvic floor dysfunction. Subjects were divided into three groups: (i) 100 without significant POP undergoing initial evaluation (group “IE”), (ii) 100 with significant POP undergoing initial evaluation (group “IE-


P”), and (iii) 97 undergoing routine 1 year postoperative follow-up after continence surgery (with or without POP surgery) (group “Post-Op”). Group IE-P had POP at or beyond the hymenal ring. The CST was performed with a comfortably full bladder, in the lying and standing positions, by a staff urogynecologist. Prolapse was reduced during testing for SUI. The CST was compared to multichannel urodynamic studies (UDS), which was considered to be the gold standard diagnostic test for SUI. UDS was performed by a specially trained nurse. The CST was compared to UDS using calculations of sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and Kappa correlation coefficient. The analysis was repeated using UDS as the test under study and CST as the gold standard. Approval was granted by the local Research Ethics Board. Results SUI was diagnosed by UDS in 37%, 36%, and 27% of each of the groups of IE, IE-P, and Post-Op, respectively. For group IE, sensitivity, specificity, PPV, NPV, and Kappa for the CST (comparing to UDS as the gold standard) were 67%, 59%, 63%, 59%, and 0.26, respectively. For group IE-P, these values were 71%, 49%, 63%, 59%, and 0.2, respectively. For group Post-Op, these values were 31%, 93%, 73%, 70%, 0.27, respectively. When the analysis was reversed, using UDS as the test under study and CST as the gold standard, sensitivity for diagnosis of SUI in the groups IE, IE-P and Post-Op was 63%, 53%, and 73%, respectively.

Table 1: Sensitivities for the diagnosis of SUI by CST and UDS Group CST (UDS as gold standard) UDS (CST as gold standard) IE 67% 63% IE-P 71% 53% Post-Op 31% 73%

Interpretation of results The CST has only an intermediate sensitivity and NPV for the diagnosis of SUI in women when compared to UDS. UDS also has poor sensitivity if CST is considered the gold standard. CST is superior in the presence of POP, possibly due to a greater ability to manually reduce the prolapse. UDS is superior as a postoperative test, possibly due to lack of observer bias by the urodynamics nurse. Concluding message With the current state of knowledge, both CST and UDS should be included in the evaluation of patients with lower urinary tract symptoms and/or POP. There is not a definitive gold standard diagnostic test for SUI. 139 Hirani K1, Rahmanou P1, Lamba A1, Dostonova A1, Chaliha C1, Khullar V1

1. Department of Urogynaecology, St. Mary's Hospital, Imperial College London DOES THE BLADDER CONTRACTILITY CHANGE WITH ANTICHOLINERGIC THERAPY IN WOMEN WITH DETRUSOR OVERACTIVITY? Hypothesis / aims of study Urgency to void is a common symptom reported by women with detrusor overactivity. The pathophysiology of how urgency may facilitate detrusor contraction is unclear, though as a general principle motor activity is closely related to sensory input by feedback mechanisms in other systems and thus the same mechanism should exist for the bladder (1). It has been suggested that sensory input of bladder wall stretch results in afferent signals of increased bladder wall tension that are transported to higher centres facilitating a micturition reflex through positive feedback (2). Women with idiopathic detrusor overactivity have more powerful bladder contractions (measured as the maximum bladder external voiding power) than controls and this is associated with the highest urge severity (1). Therefore one of the mechanisms of anticholinergic therapy may be to reduce the positive feedback mechanism and so affect bladder contraction and amplitude. The aim of our study was to assess the effect of therapeutic anticholinergic therapy on bladder contractility by evaluating contractility during voiding.


Study design, materials and methods Women were recruited from the urodynamic clinics. All had a previous diagnosis of idiopathic detrusor overactivity and reported frequency at least seven times per day, one or more episodes of urge incontinence per week, and at least seven episodes of urgency per week. Women with urodynamic stress incontinence and those with previous bladder outlet surgery were excluded. After a 2-week washout period subjects were randomised to receive propiverine 20 mg od, propiverine 15 mg tds, oxybutynin 5 mg tds or placebo for 2 weeks. After a second wash out period, they were randomised to receive 2 weeks of one of the treatments not previously used. Ambulatory urodynamic monitoring was performed according to ICS standards for 4 hours, using a standardised protocol with a fluid intake of 180mls every 30 minutes, before and after treatment. The bladder contractility index is given by the formula BCI = PdetQmax + 5Qmax (3). Data was analysed for the first 2 voids, using Statistical Package for Social Sciences (SPSS) version 12.0 for Windows. The Wilcoxon signed - rank test was used to compare pre - and post - treatment bladder contractility. A p value <0.05 was considered significant. Results Seventy-seven women were recruited. The average BCI for the first two voids was 143 (Range: 24-314). Table 1 below shows the values for BCI before and after treatment.

Table 1: The effect of anticholinergic therapy on the bladder contractility index (BCI). VOID 1 VOID 2 Treatment N Pre-

treatment mean BCI

Post-treatment mean BCI

Pre-treatment mean BCI

Post-treatment mean BCI

(Range) (Range) Significance (Range) (Range) Significance Propiverine 20mg od 37 143 138 p = 0.11 136 126 p = 0.94 (38-294) (74-291) (39-290) (24-193) Propiverine 15mg tds 36 163 155 p = 0.46 149 165 p = 0.75 (38-294) (48-314) (37-290) (61-282) Oxybutynin 5mg tds 37 150 142 p = 0.96 146 137 p = 0.88 (64-290) (56-268) (37-272) (29-301) Placebo group 22 158 143 p = 0.42 100 134 p = 0.13 (72-274) (65-300) (54-240) (32-286)

P values obtained using Wilcoxon signed – rank test. N = Number of patients. Interpretation of results The BCI was not statistically different before and after anticholinergic therapy or in response to placebo in either void. Concluding message The bladder contractility index does not seem to change in response to anticholinergic therapy suggesting that the therapeutic effect is not mediated by an effect on motor function. References

1. Neurourol Urodyn 2003; 22:223-226. 2. Am J Physiol 1986; 251:225-30. 3. BJU Int 1999; 84:14-15.

140 Diefenbach K1, Arold G1, Wollny A1, Schwantes U2, Haselmann J2, Roots I11. Institute of Clinical Pharmacology, Charité - Universitätsmedizin Berlin, 2. Medical Department, Dr. R. Pfleger Chemische Fabrik GmbH THE INFLUENCE OF ANTICHOLINERGICS USED IN INCONTINENCE TREATMENT ON SLEEP IN HEALTHY VOLUNTEERS AGED 50 YEARS AND OLDER Hypothesis / aims of study There is strong evidence of an impact on sleep structure and sleep quality under treatment with anticholinergic substances used in incontinence treatment coming from reports of neuro-psychological side-effects and case-reports of sleep disturbances as well as from parallels to other anticholinergic substances. The aim of the


study was to investigate whether sleep parameters change under treatment with oxybutynin, tolterodine and trospium in comparison to placebo within the target population for these substances, i.e. in individuals aged 50 years and older. Study design, materials and methods According to the guidelines of Good Clinical Practice (GCP) and the declaration of Helsinki a randomised, double-blind, placebo-controlled study was conducted in a cross-over-design. After an initial polysomnographic and thorough physical examination 25 healthy volunteers (13 female, 12 male) aged 51 to 65 years, without any sleep-disturbances were included in the study, one volunteer dropped-out. The subjects underwent 4 periods of 2 consecutive polysomnographic nights in the sleep-lab, always separated by 12 days washout. Each first night was for adaption, the second night was the treatment-night and was used to study the impact of the medication on sleep. Administration of medication was 2 hours before starting polysomnography. In a randomised order volunteers obtained 4 mg tolterodine, 15 mg oxybutynin, 45 mg trospium and placebo. To assess the subjective quality of sleep, a structured questionnaire had to be filled out by the volunteers before and after each polysomnographic recording. In addition “The d2 test of Attention” (d2) and a “Number Combination Test” (ZVT) were performed one hour after medication. Additionally an exploratory analysis of all objective and subjective sleep parameters as well as parameters of psychometric testing was performed using the Wilcoxon Matched-Pairs Signed-Ranks Test. All tests except that used for the primary parameters had to be interpreted on an explorative level. Results For statistics Friedman’s ANOVA was used to prove differences between the treatments. As target variable for polysomnography REM duration as a percentage of sleep duration (TST) showed statistically significant over-all differences (p=0.007) between the four treatment groups. Further analyses using the Wilcoxon Matched-Pairs Signed-Ranks Test revealed reductions in the median of REM sleep duration of 14.2% after oxybutynin (p=0.002) and of 15.2% after tolterodine (p=0.012) compared to placebo. REM duration after trospium chloride was not significantly different from placebo. A second explorative analysis revealed a non-significant (p=0.074) prolongation of REM latency (time between sleep onset and first period of REM) after intake of oxybutynin and tolterodine compared to placebo and trospium chloride. No significant changes were seen for the other secondary objective parameters: duration of various sleep stages (stage 1, stage 2, slow wave sleep (SWS)) as a percentage of sleep duration (TST), sleep latencies (sleep onset latency, SWS latency), and sleep efficiency. Subjective sleep parameters were not significantly affected by the different medications. None of the study medications influenced the cognitive skills of the volunteers. Interpretation of results Incidence and intensity of central-nervous side-effects of anticholinergic drugs depend on their pharmacokinetic and pharmacodynamic properties and can be more pronounced in the elderly, even if dosage is properly adjusted to account for age-related pharmacokinetic changes. Several authors have shown relevant neuro-psychological side-effects in elderly patients treated with tertiary anticholinergic substances as oxybutynin and tolterodine. These side-effects did not occur under treatment with the quaternary substance trospium chloride. Furthermore, sleep disturbances (pavor nocturnus) were reported in literature under oxybutynin . In healthy volunteers aged 50 years and older, we observed a significant REM sleep reduction of about 15 % and a slightly increased REM latency under oxybutynin and tolterodine compared to placebo. Under trospium chloride, REM sleep parameters were comparable to placebo. We did not observe any effect of the tested anticholinergics on cognitive parameters and subjective sleep parameters. However, an impairment of cognitive function and neuro-psychological side-effects cannot be excluded, especially when elderly patients with impaired REM sleep due to various psychic diseases (e.g. depression) and/or sleep disturbances are given oxybutynin or tolterodine. Furthermore, these drugs are used in chronic diseases and it is unknown how the effects on sleep structure influence cognitive skills in the long run. Concluding message Individuals aged 50 years and older have a distinct impairment of REM sleep under oxybutynin and tolterodine. We suggest that for patients with cognitive impairment under therapy with these anticholinergics, a switch to trospium chlorid should be taken into consideration. FUNDING: Dr. R. Pfleger Chemische Fabrik GmbH


141 Cardozo L1, Robinson D1, Drogendijk T2, for the Solifenacin Study Group 11. King's College Hospital, London, UK, 2. Yamanouchi Europe B.V., Leiderdorp, The Netherlands SOLIFENACIN STATISTICALLY SIGNIFICANTLY INCREASED CONTINENCE RATES IN SUBJECTS WITH SYMPTOMS OF THE OVERACTIVE BLADDER SYNDROME Hypothesis / aims of study Symptoms of the overactive bladder (OAB) syndrome include urgency, with or without urge incontinence, usually with frequency and nocturia. More than one third of people with OAB experience incontinence, which has a severe impact on their quality of life [1]. Solifenacin succinate is a once-daily (od) oral antimuscarinic agent evaluated for the treatment of OAB (dosed at 5 mg, the suggested starting dose, or at 10 mg). In clinical trials conducted worldwide, solifenacin treatment has demonstrated statistically significant reductions in urgency, frequency, and incontinence, the key symptoms of OAB [2, 3]. Incontinence outcomes were gathered from a pooled analysis of two pivotal studies of solifenacin and an open-label, 40-week extension of these studies designed to assess long-term efficacy and tolerability. Study design, materials and methods Data from subjects who reported incontinence episodes at baseline were combined from two 12-week, randomised, placebo-controlled, double-blind studies with comparable baseline demographics and study protocols that permitted pooling. Subjects in the extension study could maintain or adjust their solifenacin dose (between 5 mg and 10 mg) following assessment visits at weeks 16, 28, and 40. Data were collected from 3-day micturition diaries completed at multiple time points during the double-blind and open-label studies. Results From the two 12-week studies, a subset of 943 subjects (from a total population of 1640), who reported a mean number of 2.6 to 3.0 incontinence episodes per 24 hours at baseline, were evaluated. Statistically significant reductions in incontinence episodes relative to baseline were seen with solifenacin 5 mg od (−1.5) and solifenacin 10 mg od (−1.5), versus placebo (−1.0). Adjusted mean treatment differences from placebo were −0.66 (95% CI; −0.96, −0.35) and −0.60 (95% CI; −0.91, −0.30) for solifenacin 5 mg and 10 mg, respectively (P<.001 for both doses compared with placebo). In addition, 51% of subjects receiving solifenacin 5 mg od or solifenacin 10 mg od became continent (P<.01) in comparison to 38% of subjects receiving placebo after 12 weeks of treatment. A large majority (91%) of subjects who completed the 12-week studies elected to enroll in the extension study. Further reductions (−0.13) in incontinence episodes per 24 hours were observed during the extension study. After an additional 40 weeks of solifenacin treatment, the continence rate in the open-label extension study increased to 60%. The majority of adverse events (AEs) reported were mild to moderate in severity. Overall, at the end of the extension study, rates of dry mouth were 10% in subjects while receiving solifenacin 5 mg od and 17% in subjects while receiving solifenacin 10 mg od; the rate of dry mouth in the total population was 21%. Interpretation of results After 12 weeks of treatment, solifenacin 5 mg od and 10 mg od statistically significantly reduced episodes of incontinence compared with placebo in subjects with OAB. One half of the subjects treated with solifenacin achieved continence. Further reductions in incontinence episodes, as well as additional increases in the continence rate, were observed after long-term solifenacin treatment. The safety profile of patients treated with solifenacin for up to 1 year was consistent with that seen in short-term studies, suggesting that the flexible dosing offered in the extension study may be associated with improvements in therapeutic response and a favourable tolerability profile. Concluding message In contrast to prior experience with antimuscarinic therapy, the continence rate increased with duration of solifenacin treatment. References

1. How widespread are the symptoms of an overactive bladder and how are they managed? A population-based prevalence study. BJU Int. 2001;87:760-766.

2. Randomized, double-blind placebo- and tolterodine-controlled trial of the once-daily antimuscarinic agent solifenacin in patients with symptomatic overactive bladder. BJU Int. 2004;93:303-310.

3. Randomized, double-blind placebo-controlled trial of the once-daily antimuscarinic agent solifenacin succinate in patients with overactive bladder. J Urol. 2004;172 (In press).


142 Chapple C1 1. Royal Hallamshire Hospital FESOTERODINE A NEW EFFECTIVE AND WELL-TOLERATED ANTIMUSCARINIC FOR THE TREATMENT OF URGENCY-FREQUENCY SYNDROME: RESULTS OF A PHASE 2 CONTROLLED STUDY. Hypothesis / aims of study Fesoterodine is a novel derivative of 3,3-diphenylpropyl-amine developed by Schwarz Pharma for the treatment of urgency-frequency syndrome (UFS also known as overactive bladder). The drug is a potent antimuscarinic, rapidly absorbed and immediately hydrolyzed to the active metabolite, SPM 7605, without requiring hepatic metabolism. The objective of this trial was to determine the optimal dose of fesoterodine measuring efficacy, tolerability and safety in subjects with UFS. Study design, materials and methods This trial was conducted at 81 sites in Europe, Israel, and South Africa. After a 1-week placebo run-in, eligible subjects were randomized to receive placebo or 4, 8, or 12 mg of fesoterodine once daily for 12 weeks. Efficacy variables were measured as change from baseline to 12 weeks after treatment. Primary variables were change in the mean number of micturitions per 24 hours and change in the mean number of urge incontinence episodes per week. Treatment efficacy was assessed by comparing the change from baseline in a 7-day micturition diary. Safety was assessed by monitoring adverse events and changes in clinical laboratory values, vital signs, ECGs, physical and urological examinations, and residual urinary volume. Treatment tolerance was evaluated subjectively. Results A total of 728 subjects were randomized and treated; 698 subjects were evaluable for the primary efficacy analysis. The mean age was 56 (age range 18–79 years) and 84% of subjects were female.

Mean changes from baseline to end of treatment. Variable Placebo 4 mg fesoterodine 8 mg fesoterodine 12 mg fesoterodine Micturitions/24 hours Mean change Difference from placebo (ANCOVA adjusted estimate)

-1.42

-2.20 -0.72; p=0.0030*

-2.37 - 0.82; p=0.0012*

-2.41 - 0.94; p=0.0002*

Urge incontinence episodes/week Mean change Difference from placebo (ANCOVA adjusted estimate)

-10.18

-12.79 -3.96; p=0.0045

-11.79 -2.54; p=0.0521

-13.43 -4.61; p=0.0013*

P-values are one-sided; “*” means significant in the closed test procedure.

There is a rapid improvement in both primary efficacy variables within the first two weeks of double-blind treatment as contrasted to placebo. Fesoterodine treatment results show significantly greater decreases in micturition frequency than placebo at all 3 doses. Early improvements were also seen in the reduction of the number of urge urinary incontinence episodes. The reduction was also seen in the 4 mg group. The most frequently reported AE in this trial was dry mouth (placebo 9%, 4 mg 25%, 8 mg 26%) increasing to 34% in the 12 mg group. The use of a VAS (visual analogue scale) to assess dry mouth may have triggered the reporting. Dry mouth was rated as mild to moderate in most cases in the 4 and 8 mg groups. Drop out rates due to AE were 4% of subjects in placebo group, 6%, 2%, 12% in the 4 mg, 8 mg and 12 mg Fesoterodine groups, respectively.

Adverse events with a frequency greater than 1% in any treatment group

Adverse events > 1 % Placebo (N=183)

Fesoterodine 4mg (N=186)



Dry mouth* 9% 25% 26% 34% Headache 16% 17% 16% 15% Influenza-like symptoms 8% 9% 4% 4% Abdominal pain 4% 3% 8% 8% Nausea 7% 5% 2% 6% Constipation 3% 2% 3% 6% Back pain 3% 3% 4% 2% Coughing 4% 3% <1% 3% Dizziness 3% 4% 1% 2% Abnormal vision 1% 0% 0% 1%

*after randomisation


All other adverse events were in the range of placebo for all the treatment groups. Low rates were seen for constipation and vision disorders, which were in the placebo range. Fesoterodine had no clinically relevant effects on vital signs or ECG parameters. Based on patient assessments, the doses of 4 mg and 8 mg showed the best efficacy/tolerance ratios. Interpretation of results Fesoterodine once daily is an effective antimuscarinic agent in the treatment of urgency-frequency syndrome at all of the three doses tested. It significantly improved micturition frequency and urge incontinence episodes as compared to placebo. Fesoterodine was generally well tolerated, and no safety concerns were raised. Except for dry mouth all side effects were low or in the range of placebo, including constipation and vision disorders. Concluding message In conclusion, fesoterodine is a potent and well-tolerated antimuscarinic in all doses tested (4 mg, 8 mg and 12 mg). The most favourable efficacy-safety ratio was observed in the 4 and 8 mg groups. 143 Juenemann K1, Hessdoerfer E2, Unamba-Oparah I3, Berse M4, Bruenjes R5, Madersbacher H6, Gramatté T5

1. Dept. Urology, Univ Hosp Kiel, Germany, 2. Dept. Urology, Berlin, Germany, 3. Dept. Urology, Voerde, Germany, 4. Dept. Urology, Duisburg, Germany, 5. APOGEPHA Dresden, Germany, 6. Neurourology Unit, Univ Hosp of Innsbruck, Austria PROPIVERINE HYDROCHLORIDE IMMEDIATE (IR) AND EXTENDED RELEASE (ER): COMPARISON OF EFFICACY AND TOLERABILITY IN PATIENTS WITH OVERACTIVE BLADDER Aims of study The primary objective was to evaluate the efficacy of propiverine hydrochloride immediate release (IR) and propiverine hydrochloride extended release (ER) in comparison with placebo in patients with overactive bladder in terms of incontinence episodes/24 hours. Secondary objectives were number of micturitions/24 hours, urge episodes/24 hours, volume of micturition, efficacy evaluation by patient and investigator, quality of life (King’s Health Questionnaire), adverse events (AEs), blood pressure/pulse rate, ECG, haematology, clinical chemistry and urinalysis, evaluation of tolerability by patient and investigator. Materials and methods This clinical study was designed as a double-blind, double-dummy, randomised, placebo-controlled study with 3 parallel groups comparing IR 15 mg twice daily, ER 30 mg once daily and placebo at a ratio of 2:2:1.After a run-in period of 7 days, the patients were treated for 32 days with regular assessments of efficacy and tolerability using pre-post comparisons. The safety population consisted of 988 patients (89.5% females and 10.5% males). Its mean age was 56.1 years and its mean BMI was 26.6 kg/m2 in the males and 27.0 kg/m2 in the females (comparable between the groups). The ITT population consisted of 786, and the pp population of 735 patients. A total of 973 (98.5%) patients experienced their incontinence with urge. Results Efficacy;In the ITT population the baseline values for the incontinence episodes within 24 hours were comparable (3.29 in the IR group, 3.38 in the ER group, 3.50 in the placebo group). The number of incontinence episodes decreased by 2.26 in the IR group, by 2.46 in the ER group, and by 1.75 in the placebo group. Changes were statistically significantly different for both treatments versus placebo (p<0.0001). The number of micturitions within 24 hours was statistically significantly (p<0.001) more reduced in both propiverine groups than in the placebo group. The number of urge episodes within 24 hours was statistically significantly (p<0.05) more reduced in both propiverine groups than in the placebo group. The treatment groups did not differ regarding the increase in volume of micturitions within 24 hours. The mean volume of the single micturitions increased statistically significantly more in both propiverine groups than in the placebo group, although the liquid intake was comparable between groups. The efficacy assessed by the investigators and patients was statistically significantly better in both propiverine groups than in the placebo groups. The improvement in QoL was less consistent, although the propiverine groups were slightly better than the placebo


group. Safety; 38.5% of the patients experienced AEs in the IR group, 34.3% of the patients in the ER group, and 20.3% of the patients in the placebo group. 26 (2.6%) patients dropped out prematurely due to a AE: 14 (3.5%) in the IR group, 11 (2.8%) in the ER group, and 1 (0.5%) in the placebo group. Gastrointestinal disorders and nervous system disorders were the most frequent AEs leading to withdrawal from the study. The difference in incidence of AEs between propiverine and placebo was mainly caused by propiverine's anticholinergic effects. The most frequent adverse event was dry mouth with 22.8 % of the patients of the IR group, 21.7 % of the patients of the ER group and 6.4 % of the placebo group. “Eye disorders” were experienced by 6.6% of the patients of the IR group, 7.2% of the ER group and 2.5% of the placebo group. All other system organ classes accounted for less than 5% of the patients each. Other safety parameters (blood pressure/pulse rate, ECG, laboratory, urinalysis) did not show any results of concern. The overall tolerability was rated very good or good by 85% of the investigators and patients. Concluding message Propiverine IR 15 mg b.i.d. and propiverine ER 30 mg s.i.d. reduce effectively the number of incontinence episodes per 24 hours within a treatment period of 32 days. Both formulations also decrease the number of urge episodes per 24 hours.They decrease the number of micturitions within 24 hours resulting in an increase of the volume of single micturitions without increase of the total 24 h urine output and despite unchanged liquid intake. Both formulations are safe. FUNDING: Apogepha Arzneimittel GmbH 144 Rudy D1, Cline K2, Goldberg K3, Harris R 41. North Texas Clinical Research, 2. Regional Urology, LLC, 3. Texas Urology Research, 4. RMD Clinical Research Institute, LLC A MULTICENTER, RANDOMIZED, PLACEBO-CONTROLLED TRIAL OF TROSPIUM CHLORIDE IN OVERACTIVE BLADDER PATIENTS Hypothesis / aims of study Trospium chloride (TCl), a quarternary amine, is an antimuscarinic agent marketed in Europe for the treatment of patients with overactive bladder symptoms. A large US multicenter trial was conducted to determine the effects of TCl when given as 20 mg tablets versus placebo (pbo), twice daily, on urgency, 24-hour frequency, urinary incontinence (UI) and urgency severity associated with overactive bladder, specifically evaluating the time to onset of these parameters over a 12-week treatment period. Study design, materials and methods This was a multicenter, parallel, randomized, double-blind, placebo-controlled trial in patients with overactive bladder (OAB). Following a 3-week washout period (1-week for naïve patients) and 7-day baseline diary, 24-hour frequency > 10 and > 1 UI/day were required for inclusion, prior to receiving either TCl 20 mg bid or pbo for 12 weeks. Interim visits were performed at Weeks 1 and 4. A 7-day diary was collected the week prior to study visits to record each micturition and associated urgency as measured by the IUSS (urgency severity scale), and UI episodes/day, as well as urine volume on Days 6 & 7. Efficacy analyses were done using the intent-to-treat (ITT) with the last observation carried forward (LOCF) data sets. ANOVA models or, where appropriate, rank ANOVA were used. The time to onset of effect was analyzed across study weeks and during Week 1 using reverse stepwise methodology. Results A total of 658 patients (trospium 329 patients, placebo 329 patients) were randomly assigned on a 1:1 ratio to receive either trospium chloride 20 mg or placebo twice daily. The patient population was predominantly female (trospium 81.2%; placebo 81.8%) and Caucasian (trospium 86.3%; placebo 91.2%). The mean age in the trospium chloride group was 61.1 years and 61.0 years in the placebo group. The treatment groups were similar with respect to demographic and baseline characteristics. Patients treated with trospium chloride demonstrated statistically significant reductions in average 24-hour frequency, urinary incontinence episodes, urgency, and urgency severity, while volume voided/void was significantly increased at Weeks 1, 4 and 12


when compared with the placebo group (see Table 1). The rate of improvement/response over time was analyzed to determine onset of effect across study weeks for effect on 24-hour frequency, urgency severity, urge frequency, volume voided, and frequency of urge incontinence episodes. These analyses show that the onset of effect for TCl for significantly decreasing the 24-hour frequency, decreasing urgency severity, decreasing urge frequency, increasing the volume voided per toilet void, and decreasing the number of daily urge incontinence episodes occur within the first week of treatment. Analysis within the first week of treatment revealed that the effect of trospium was significant on 24-hour frequency and urinary incontinence within the first few days. The most common adverse events were dry mouth (19.8% TCl vs 5.2% pbo) and constipation (10.9% TCl vs 5.8% pbo). Patients discontinued due to AEs were 7.3% for TCl vs. 4.6% for pbo. Interpretation of results The findings for these efficacy variables are consistent with the expected pharmacodynamic effects of TCl. Anticholinergic relaxation of the detrusor muscle would be expected to increase maximum bladder capacity and increase the bladder volume at which the first unstable bladder contraction occurred. This is additionally supported by the clinical effects of decreased 24-hour frequency, decreased urgency severity, decreased urge frequency, increased volume voided, and decreased average daily urge incontinence episodes. While these effects were evident within the first week, the previously noted parameters, in general, continued to improve at each subsequent study visit week.Table 1:

Summary of results for efficacy endpoints – ITT population Mean change from baseline

Placebo Trospium P-value Efficacy endpoint Week N = 325 N = 323 24-hour frequency N = 325 N = 323

Baseline 13.17 12.94 0.3169 Change from baseline 1 -0.96 -1.42 0.0039

4 -1.55 -2.34 <0.0001 12 -1.76 -2.67 <0.0001

Urgency severity score associated with toilet voidsa N = 325 N = 323


4 -0.04 -0.19 <0.0001 12 -0.02 -0.21 <0.0001

Volume voided (mL) per toilet void/24 hoursa N = 320 N = 319

Baseline 154.64 154.80 0.9667 Change from baseline 1 6.05 29.23 <0.0001

4 9.45 39.50 <0.0001 12 9.44 35.59 <0.0001

Urgency events with toilet voidsa N = 325 N = 323


4 -1.43 -2.48 <0.0001 12 -1.53 -2.76 <0.0001

Number of daily urge urinary incontinence episodesb N = 325 N = 323

Baseline 3.90 3.84 0.9849 % Change from baseline 1 -24.1 -44.8 <0.0001

4 -40.9 -59.7 <0.0001 12 -43.6 -65.9 <0.0001 a. Treatment differences assessed by analysis of variance for ITT:LOCF data set. b. Treatment differences assessed by rank analysis of variance for ITT:LOCF data set.

Concluding message Trospium chloride was found to be effective in treating patients with OAB associated with urge incontinence. TCl significantly improved OAB symptoms within the first few days of beginning treatment and was found to be well tolerated. FUNDING: Indevus Pharmaceuticals, Inc.


145 Hill S1, Khullar V2

1. Department of Obstetrics and Gynaecology, Queen's Park Hospital, Blackburn, UK, 2. St Mary's NHS Trust (Imperial College, London), UK DARIFENACIN, A MUSCARINIC RECEPTOR ANTAGONIST WITH SELECTIVITY FOR M3 RECEPTORS, REDUCES INCONTINENCE AND NOCTURIA IN PATIENTS WITH OVERACTIVE BLADDER Hypothesis / aims of study This study evaluated the effect of darifenacin, a new muscarinic M3 selective receptor antagonist (M3 SRA), on the symptoms of overactive bladder (OAB). OAB is a common and often highly debilitating medical complaint, defined as urinary urgency, with or without urge incontinence, usually with frequency and nocturia (the need to wake at night one or more times to void). Study design, materials and methods This multicentre, double-blind, randomised, placebo-controlled study enrolled 439 patients who had suffered from OAB symptoms for ≥6 months. After a 2-week placebo run-in, patients were randomised to receive 12 weeks of treatment with oral darifenacin controlled-release (CR) tablets once daily (q.d.) at doses of 7.5 mg (n=108), 15 mg (n=107), or 30 mg (n=115), or matching placebo (n=109). Efficacy was evaluated from OAB symptoms recorded daily using a validated electronic diary.1 The primary efficacy variable was the change from baseline in the number of incontinence episodes per week at 12 weeks. Secondary efficacy variables included the number of OAB-related nocturnal awakenings per week. Tolerability and safety were also assessed. Results Results are presented for the proposed market doses of darifenacin (7.5 mg and 15 mg). At week 12, treatment with darifenacin was associated with a dose-related reduction from baseline in the number of incontinence episodes per week with a median percentage reduction of 68.7% and 76.5% with darifenacin 7.5 mg and 15 mg, respectively (Figure 1).

The reduction in incontinence episodes with darifenacin was significantly superior to placebo at all dose levels, and this was noted as early as week 2 of treatment (Figure 1). In addition, there was a significant reduction in the number of nocturnal awakenings due to OAB experienced by patients treated with either darifenacin 7.5 mg or 15 mg compared with placebo (Figure 2).

M

edia

n %

cha

nge

from

bas

elin

e in

num

ber o

f in

cont

inen

ce e

piso

des

per w

eek

*p<0.05, **p<0.01, ***p<0.001 using Wilcoxon rank-sum test stratified by baseline for testing treatment difference versus placebo. n numbers may be lower than randomised numbers because patients were only included in the efficacy analysis if they had a baseline and any post-baseline diary data.

0 At ks2 wee At 12 weeks

Darifenacin Darifenacin Figure 1. Reduction in frequency of incontinence episodes

Placebo(n=108)

7.5 mg q.d.

(n=107)Placebo (n=108)

7.5 mg q.d.

(n=107)

15 mg q.d.

(n=106)

-48.7*

*-43.1

-76.5 *

-68.7*

-46.0

-31.5

-20

-40

-60

-80

-100

15 mg q.d.


Figure 2. Reduction in frequency of nocturnal awakenings at week 12

Darifenacin 15 mg q.d. (n=105)

Darifenacin7.5 mg q.d. (n=106)

Placebo (n=106)

0

-5

-10

-15

-20

-25 -22.7*

-22.1*

-3.6

*p<0.05 using Wilcoxon rank-sum test stratified by baseline for testing treatment difference versus placebo. n numbers may be lower than randomised numbers because patients were only included in the efficacy analysis if they had a baseline and any post-baseline diary data.

Med

ian

% c

hang

e fro

m

base

line

The overall incidence of all-causality adverse events, the majority of which were mild to moderate in severity, was 57.4%, 68.2% and 49.5% with darifenacin 7.5 mg and 15 mg and placebo, respectively. The most frequent events were dry mouth and constipation. The central nervous system (CNS) and cardiovascular adverse event profile was similar to that of placebo. For all treatment groups there were no clinically relevant changes with regard to laboratory tests or vital signs. Interpretation of results Darifenacin at doses of 7.5 mg and 15 mg provided a significant, dose-related improvement in the major symptoms of OAB, including reduced frequency of incontinence episodes, and was well tolerated. Darifenacin also significantly reduced nocturia, a particularly bothersome symptom which is associated with an increased risk of injury due to falls during night-time visits to the bathroom.2 The CNS and cardiovascular safety profile are suggestive of additional benefits arising from the M3 selectivity of darifenacin. Concluding message The findings in this placebo-controlled study show that the M3 SRA darifenacin provides an effective and well tolerated new option for OAB therapy. References 1. Assessment of an electronic daily diary in patients with overactive bladder. British Journal of Urology International 2003;31:647-52. 2. Urinary incontinence: does it increase risk for falls and fractures? Study of Osteoporotic Fractures Research Group. Journal of the

American Geriatrics Society 2000;48:721-5. FUNDING: Novartis Pharma AG, Switzerland 146 Mattiasson A 1, Lundegaard Christensen T2, Poulsen P B2, Tangen T3

1. Dept. of Urology, Lund Sweden, 2. MUUSMANN Research & Consulting, Denmark, 3. Serud Medical Research, Norway COST-EFFECTIVENESS OF DESMOPRESSIN TABLETS (MINIRIN®) AS ADJUNCTIVE THERAPY TO BEHAVIOURAL CHANGES IN THE TREATMENT OF NOCTURIA IN NORWAY. Hypothesis / aims of study Previous studies have shown that untreated nocturia is associated with reduced health related quality of life and loss of productivity (working hours per week) [1]. The aim of the present study was to analyse the cost-effectiveness of treatment with desmopressin as adjunctive therapy to behavioural changes for the indication ‘nocturia in adults’ in Norway.


Study design, materials and methods Effectiveness data was obtained from three randomised clinical trials (n=237). Patients were assigned to either treatment with desmopressin as adjunctive therapy to behavioural changes or to behavioural changes alone [2,3]. Data on direct costs was partly collected in the clinical trials (piggybacked), partly estimated by a Norwegian expert panel. Quality adjusted Life years (HRQOL / QALY) and productivity gains were estimated on the basis of a Swedish population study (n=283) [1]. All analyses were conducted for a group of younger adults (<65 years) on the basis of the recommended treatment age and the approved indication for desmopressin in Norway. The cost calculation was conducted within a societal and a healthcare sector perspective. The applied methods comply with the Norwegian pharmacoeconomic guidelines. Results When comparing desmopressin as adjunctive treatment with behavioural changes alone (incremental effects) in the population of younger adults (men/women), the number of voids per night decreased (-0.66 / -0.59 voids), while the duration of first sleep (+ 69 / +82 minutes), productivity (+ 1.22 / + 1.65 working hours per week) and HRQOL (+0.017 / +0.016 QALY) all increased during one year. Within a societal perspective, the costs of the desmopressin treatment were outweighed by the potential productivity gains yielding a yearly potential saving of NOK 1,804 (~ € 214) per male patient and NOK 537 (~ € 64) per female patient. In a narrower healthcare sector perspective (productivity gains omitted), desmopressin as adjunctive therapy to behavioural therapy was slightly more expensive than behavioural therapy alone when treating nocturia. The incremental cost was estimated to NOK 8,657 (~ € 1.027). Several sensitivity analyses showed robust results. Interpretation of results Cost-effectiveness compares costs with the different measures of effectiveness. When analysing within a societal perspective, desmopressin was a dominant treatment (cheaper and more effective) compared to behavioural change alone. However, when analysing within a healthcare sector perspective, desmopressin as adjunctive therapy was more effective but also more expensive than behavioural changes alone. The relevant question in this case is “How much is gained per NOK (€) spent on desmopressin?” The yearly healthcare sector price for one void less per night was estimated to approximately NOK 13,500 (~ € 1.602). Concluding message Behavioural change is the first-line treatment option for patients suffering from nocturia. However, using desmopressin as adjunctive therapy to behavioural change increases the patients’ quality of life at a small extra cost for the healthcare sector. If productivity gains are included in the analysis, desmopressin becomes dominant (less costly and more effective). Desmopressin is therefore a suitable treatment option for adult patients in Norway suffering from nocturia. References

1. Productivity, vitality and utility in a group of healthy professionally active individuals with nocturia; BJU Int 2003; 91 (3), 190 2. Efficacy of desmopressin in the treatment of nocturia: a double-blind placebo-controlled study in men; BJU int 2002;89:855-62.

(NOCT 2a) 3. Efficacy of desmopressin (Minirin) in the treatment of nocturia: a double-blind placebo-controlled study in women; Am J Obstet

Gynecol 2003;189:1106-13 FUNDING: Ferring Pharmaceuticals A/S 147 Rios L1, Mattos Jr. D 2, Panhoca R 3, Srougi M 4, Bruschini H 41. Federal University of São Paulo and Hospital do Servidor Público Estadual de São Paulo, 2. Hospital do Servidor Publico Estadual de São Paulo, 3. Hospital do Servidor Público Estadual de São Paulo, 4. Federal University of São Paulo INTRAVESICAL RESINIFERATOXIN FOR THE TREATMENT OF IDIOPATIC DETRUSOR OVERACTIVITY IN WOMEN: A RANDOMIZED PLACEBO CONTROLLED STUDY Hypothesis / aims of study Idiopathic detrusor overactivity (IDO) is a highly prevalent condition, which may cause profound impact in the quality of life (QoL), of affected patients. The primary therapeutic approach to IDO is usually treatment with anticholinergic drugs, bladder retraining and physical therapy either alone or in combination. Unfortunately, those therapies are many times unsatisfactory in terms of clinical benefits or limited by troublesome side effects. Recently intravesical instillation of capsaicin and resiniferatoxin for the treatment of overactive bladder


has been proposed. These substances, collectively referred as vaniloids, share a common functional ability to desensitise C-fibbers that results in blocking of presumed abnormal afferent input from the bladder to the spinal cord.1,2 RTX is an ultrapotent analogue of capsaicin naturally occurring in the latex of a cactus-like plant named Euphorbia resinifera. Unlike capsaicin RTX has the advantage of being less painful when instilled in the bladder making the treatment easily feasible under topical analgesia. 2 We present the results of a randomised, double blind, placebo controlled study on women suffering from idiophatic detrusor overactivity submitted to intravesical treatment with RTX 50 nM in saline and 10% ethanol or to saline and 10% ethanol only (placebo). Study design, materials and methods We prospectively randomised 60 women into 2 groups to receive a single dose of 50 nM resiniferatoxin in 10% ethanol and saline (group 1) or a 10% ethanol and saline solution (group2) intravesically for 30 minutes. All patients had at least 6-month history of frequency, urgency, nocturia, with or without urge-incontinence, idiopathic detrusor overactivity and no history of neurologic disease, infra-vesical obstruction, recent or present urinary tract infection, stone disease, radiation therapy or severe pelvic organ prolapse. We used voiding questionnaire, bladder diary, QoL questionnaire, and pad-tests to evaluate pre-treatment voiding patterns. Biochemical and haematological profiles were obtained pre- and 30 days post-treatment to check the safety of the drug. Patients were clinically evaluated 7 days after instillation and the complete pre-treatment work-up was repeated at 30 days after treatment.. The study was approved by the ethical committee of both institutions.Statistical analysis was made with qui-square test for proportions, ANOVA for longitudinal repetitive data, “t”test for independent groups and Mann-Whitney and Wilcoxon tests for scores. The results are expressed as means plus or minus standard deviation. Results The two groups were homogeneous regarding age, race, clinical, surgical, obstetric and gynaecologic antecedents. There were four patients lost to follow-up in group 2 and one patient in group 1 who where excluded from further analysis. The voiding symptom profile and the urodynamic patterns were also homogeneous between the two groups except for the number of incontinence episodes (lower in group 1). The daytime frequency decreased from a median of 9,67 _+ 2,89 voids to 8,94 _+ 2,77 in the RTX group and from 10,03 +- 2,72 to 8,90 +- 2,76 (p=0,027) in the placebo group; the number of incontinence episodes decreased from a median of 3,01 +- 2,51 episodes to 2,59 +- 3,06 in the RTX group and from 5,47 +- 3,54 to 4,27 +- 3,86 in the placebo group (p= 0,014); the number of night voidings decreased from a median of 2,18 +- 1,02 voids to 1,68 +- 1,15 in the RTX group and from 2,32 +- 1,23 to 1,82 +- 1,12 in the placebo group (p = 0,001). The patient self-reported sensation of improvement was not different between groups I and II as well (p = 0,43). The functional cistometric capacity increased from 111,4 +- 67,8 ml to 149,36 +- 95,7 in group I and from 125,4 +- 74,3 to 179,5 +- 118,9 in group II (p = 0,06); the maximal cistometric capacity increased from 281,6 +- 182,1 ml to 301 +- 159,9 in group I and from 244,3 +- 91 ml to 272,6 +- 107,2 in group II (p = 0,13). Although significant differences were found in the parameters daytime frequency, number of incontinence episodes, night-time voidings and functional cistometric capacity when comparing pre and post treatment status in both groups, there were no statistically significant differences between patients from group I (RTX) when compared to group II (placebo) in any of those parameters (p = 0,80; p = 0,22; p = 0,61 and p = 0,24 respectively). There were no statistically significant differences between the haematological and biochemical profile before and after treatment in any of the groups. Interpretation of results Curiously both RTX and placebo equally improved parameters such as daytime frequency, number of incontinence episodes, nocturia, patient perception of improvement, functional and maximal cistometric capacity. Although both treatments promote statistically significant improvement in the clinical and urodynamic parameters studied the instillation of RTX 50 nM showed no advantage over the placebo in women with idiopathic detrusor overactivity. Concluding message The use of resiniferatoxin for the treatment of women with IDO was not better than placebo in this randomised, double-blind, placebo-controlled study. References

1. The effect of intravesical resiniferatoxin in patientes with idiopathic detrusor instability suggests that involuntary contractions are triggered by C-fibber input. J Urol 168, 575-579, 2002

2. Bladder afferents and their role in the overactive bladder. Urology 59 (Suppl 5a): 37-42, 2002


148 Payne C1, Mosbaugh P2, Forrest J3, Evans R3, Frumkin L4

1. Stanford University, 2. Indiana University, 3. none, 4. ICOS Corporation PHASE II SAFETY AND EFFICACY STUDY OF SINGLE DOSE OF INTRAVESICAL RESINIFERATOXIN (RTX) IN PATIENTS WITH INTERSTITIAL CYSTITIS Hypothesis / aims of study Interstitial cystitis (IC) is a painful bladder condition of unknown etiology and poorly understood pathophysiology. There is no uniformly successful treatment. Interest in using vanilloid receptor (VR1) agents to treat bladder pain is based on in vitro and clinical observations [1,2], which suggest that these agents may reduce pain due to a blocking or desensitization effect on C-fibers. Based on these factors, a randomized, placebo-controlled, multicenter, Phase II clinical trial of the VR1 agonist resiniferatoxin (RTX) was undertaken. We hypothesized that RTX would be an effective agent for patients with IC by desensitizing bladder C-fibers that transmit painful stimuli producing urinary frequency and urgency. Study design, materials and methods Eligible subjects had IC diagnosed by cystoscopy with bladder overdistention under anesthesia, no other disease process to explain the symptoms as listed in the NIDDK exclusion criteria [3], and current active symptoms manifest by a pain score of ≥ 4 (on a 9-point scale) and urinary frequency of ≥ 8/day while awake. Urodynamic studies were not performed. Subjects were randomized to one of four treatment groups: placebo, RTX 10 nM, RTX 50 nM, RTX 100 nM. All treatments were given as a single 50 cc instillation to be held in the bladder for 30 min in an office setting after anesthetizing the bladder with topical lidocaine. Supplemental analgesia was permitted but conscious sedation was not employed. Assessments were performed at 1, 4, 8, and 12 weeks. The primary efficacy endpoint was the Global Response Assessment (GRA) at week 4, a 7-point symmetrical scale ranging from markedly worse (score of 1) to markedly improved (score of 7). Secondary efficacy endpoints included percentage of subjects either moderately or markedly improved on GRA at week 4 (Responders), percentage of subjects with ≥ 50% reduction in pain at week 4, voiding diary variables, and the O’Leary-Sant Symptom and Problem Indices. Tolerability was assessed by the percentage of patients able to hold study drug for the required 30 minute treatment and instillation pain. Results Detailed results are displayed below. 163 subjects were recruited from 30 clinical centers; baseline disease severity and demographic factors were well balanced between the four treatment arms. There was no evidence of efficacy at any dose studied in overall symptoms, frequency, urgency, nocturia, or average voided volumes. There was no overall improvement in pain recorded in diaries. RTX resulted in a dose-dependent increase in pain during instillation and pain-related adverse events. The ability to retain study drug was improved by changing from lidocaine 2% 50 mL held for 10 min to 4% 100 mL held for 30 min (data not shown). There was one treatment-related serious adverse event (lower abdominal pain), occurring with RTX 10 nM.

Group (n) Mean (SD)

GRA (Wk 4)

% Responders(Wk 4)

% Subjects with ≥ 50% Pain Reduction

(Wk 4)

Mean (SD) Pain With Instillation

% Subjects with Adverse Event

Pain

% Subjects Unable to

Retain Study Drug

Placebo (43) 4.7 (1.6) 32.6% 23.3% 4.3 (2.7) 52.3% 4.5% 10 nM RTX (43) 4.7 (1.2) 25.6% 18.6% 5.5 (2.4) 72.1% 19% 50 nM RTX (41) 4.7 (1.3) 24.4% 31.7% 6.2 (2.3) 75.6% 29% 100 nM RTX (35) 4.6 (1.3) 20.0% 11.4% 6.7 (2.1) 80.0% 23%

Interpretation of results Despite the encouraging in vitro and pilot clinical work previously reported, a single dose of intravesical RTX was not effective in this large, controlled trial of refractory IC patients. Vanilloids as a class are associated with pain upon application. As such, it appears that RTX was delivered to the bladder sensory neurons based on dose-dependent instillation pain responses. Concluding message In the largest prospective, randomized clinical trial reported to date with intravesical vanilloids, RTX was safe but not effective in a group of 163 patients with refractory IC. A substantial percentage of subjects receiving


RTX experienced dose-dependant pain during instillation, which was improved by changing the pretreatment analgesia regimen. References

1. J Urol. 2000 Sep;164 (3 Pt 1):676-9 2. Pharmacol Rev. 1999 Jun; 51 (2): 159-212. 3. J Urol. 1988 Jul;140 (1):203-6.

FUNDING: ICOS Corporation 149 Freeman R 1, Adekanmi O2, Waterfield M1, Waterfield A1, Bishop R1, Zajicek J3

1. Urogynaecology Unit, Derriford Hospital, Plymouth UK., 2. Urogynaecology Unit, Derriford Hospital, Plymouth UK., 3. Peninsula Medical School, Plymouth UK. THE EFFECT OF CANNABINOIDS ON LOWER URINARY TRACT SYMPTOMS IN MULTIPLE SCLEROSIS: A RANDOMISED PLACEBO CONTROLLED TRIAL (CAMS-LUTS STUDY) Hypothesis / aims of study Urinary incontinence affects up to 80% of patients with Multiple sclerosis (MS). Anecdotal reports suggest that cannabis might be beneficial for lower urinary tract symptoms in MS. The Cannabinoids in Multiple Sclerosis, Lower Urinary Tract Symptoms (CAMS-LUTS) study was designed as a subsidiary study to the multicentre randomised placebo controlled Cannabinoids in Multiple Sclerosis (CAMS) study, to test the hypothesis that cannabinoids reduce episodes of urinary urge incontinence, increase functional bladder capacity and improve urodynamic parameters i.e. cystometric capacity, the number and magnitude of overactive detrusor contractions while not adversely affecting voiding function. Study design, materials and methods Six hundred and fifty seven patients randomised to receive oral cannabis extract, ∆9-tetrahydrocannabinol (∆9-THC) or matched placebo in a multicentre randomised placebo-controlled trial of cannabinoids for the treatment of spasticity and other symptoms related to multiple sclerosis (CAMS Study) were asked to complete urinary incontinence diaries and quality of life questionnaires. The primary outcome for this study investigating the effects of cannabinoids on lower urinary tract symptoms in multiple sclerosis (CAMS/LUTS) was reduction in urge incontinence episodes. In the study, a subgroup of forty-two patients underwent urodynamic studies and urinary pad tests. Results There was a significant reduction in urge incontinence episodes in the treatment groups compared with placebo (Cannabis extract 38% reduction, ∆ 9-THC 33% reduction, and Placebo 18% reduction) from baseline. There were no changes on the quality of life measure used, and there was no evidence of a treatment effect in any of the urodynamic outcomes, but for pad test weight the active groups showed a significant treatment effect when compared with placebo (mean reduction of 43·88ml for active treatment, mean increase of 8·27ml for placebo (Mean difference = 52.15ml, 95% CI = 13.38 – 90.92ml, p=0·001). Interpretation of results The findings provide evidence for a symptomatic improvement of urinary urge incontinence with cannabinoids in patients with MS. Concluding message Our results demonstrate a reduction in urge incontinence episodes measured by patient diary recording, with a reduced pad test loss in the urodynamic substudy in patients with MS treated with cannabinoids. FUNDING: Multiple Sclerosis Society (UK)


150 Apostolidis A1, Popat R2, Yiangou Y 3, Dasgupta P4, Anand P3, Fowler C J2

1. The National Hosp for Neurology and Neurosurgery,UCLH & The Hammersmith Hosp, Imperial Coll, 2. The National Hosp for Neurology and Neurosurgery,UCLH , 3. The Hammersmith Hosp, Imperial College London, 4. Guys' and St. Thomas' Hosp A POSSIBLE EXPLANATION FOR THE EXCEPTIONAL EFFICACY OF BOTULINUM TOXIN TREATMENT FOR DETRUSOR OVERACTIVITY Hypothesis / aims of study Improved cystometric parameters of patients with intractable detrusor overactivity (DO) successfully treated with intra-detrusor injections of botulinum toxin type A (BoTx/A) are accompanied by an early and significant reduction in their sensations of urinary urgency. This suggests an effect of BoTx/A on afferent bladder pathways and animal studies of BoTx/A have recently shown that it inhibits the release of sensory neurotransmitters from dorsal root ganglia and has an anti-nociceptive effect in an animal pain model. A suppression of ACh release by BoTx/A has also been shown in rat detrusor strips. We focused our investigation on the possible mechanism of action of BoTx/A on the bladder afferents, studying the changes in the suburothelial innervation of patients with neurogenic or idiopathic DO (NDO/IDO) treated with BoTx/A, using the pan-neuronal marker PGP9.5, the afferent markers TRPV1 and P2X3, and acetylcholinesterase (AChE). Study design, materials and methods Flexible cystoscopic bladder biopsies were obtained from 38 patients, 22 with NDO and 16 with IDO, who were treated with intra-detrusor injections of BoTx/A. Biopsies were taken at baseline and at 4 and 16 weeks post treatment. All patients responded to treatment, showing sustained clinical and urodynamic improvement at 16-week follow-up. The improvement in sensation of urgency, quantified as change in number of micturition episodes associated with urgency per 24 hours, was dramatic at 4/52 (8.77 ± 0.73 baseline vs 2.76 ± 0.69, P<0.0001) and sustained at 16/52 (2.63 ± 0.55, P<0.0001). Control tissue was obtained from 13 subjects with no symptoms of bladder overactivity. Specimens were fixed in 4% w/v paraformaldehyde and sections were incubated with specific antibodies to PGP9.5, AChE, TRPV1 and P2X3. PGP9.5 immunoreactivity (IR) was quantified by image analysis and expressed as % red area. A scale of nerve fibre density ranging between 0-3 was used for AChE, TRPV1 and P2X3 fibre staining. The paired t test and Mann Whitney test were used for statistical analysis, with significance determined at P values <0.05. Results An increase in suburothelial fibres expressing TRPV1 and/or P2X3 in patients with NDO has previously been reported and this observation was confirmed in the present study; the density for P2X3-IR fibres being 1.35±0.13 (mean ± SEM) in NDO bladders compared to 0.86±0.17 (P=0.037) in patients with IDO and 0.47±0.09 (P<0.0001) in controls (Figure 1), and TRPV1-IR fibres being 0.555 ± 0.130 compared to controls (0.166 ± 0.09), although this was not statistically significant (P=0.17) (Figure 2). No difference in AChE (+) nerve fibre density was found between control (0.72 ± 0.25) and overactive bladders (0.93 ± 0.12).

P2X3 and BoTx/A

Controls Pre 4/52 Post 16/52 post0.0

0.5

1.0

1.5

Ner

ve fi

bre

dens

ity

TRPV1 and BoTx/A

Controls Baseline 4/52 Post 16/52 Post0.00

0.25

0.50

0.75

Ner

ve fi

bre

dens

ity

Figure 1. Figure 2.

Four weeks (4/52) after treatment with BoTx/A, PGP9.5 values remained unchanged in n=27 available follow-up biopsies (2.04 ± 0.24 vs 1.85 ± 0.22, P=0.39), and also at 16/52 (1.63 ± 0.22 vs pre: 1.98 ± 0.33, P=0.35,


n=19 available biopsies). No change was found in AChE-IR nerve fibres at 4/52 follow-up (0.91 ± 0.15) compared to baseline values (0.96 ± 0.14; P=0.84) for 30 subjects, or at 16/52 follow-up for 20 available biopsies (0.68 ± 0.16 vs 0.97 ± 0.14, P=0.18). However, a significant decrease was noted for P2X3-IR suburothelial fibres at 4/52 (1.28 ± 0.13 vs 0.80±0.11, P=0.01, n=29), with a further decrease at 16/52 (0.51±0.12, P=0.006, n=19)(Figure 1). TRPV1-expressing fibres showed a trend to decrease at 4/52 post-BoTx/A (0.47 ± 0.11 vs 0.27 ± 0.05), which became significant only at 16/52 (0.11 ± 0.04, P=0.0004) (Figure 2). Interpretation of results Our findings suggest that successful BoTx/A treatment of overactive bladders is not associated with substantial suburothelial neuronal or cholinergic fibre degeneration or sprouting. However intra-detrusor BoTx/A injections do result in a significant decrease in TRPV1 and/or P2X3 expressing fibres, or at least in the level of expression of these receptors. This effect may be secondary to a reduction in the efferent input to the detrusor, reducing overactivity and the production/uptake of neurotrophic factors, which regulate the expression of TRPV1 and/or P2X3. However, this decrease taken in conjunction with the clinical reduction in urinary urgency and the emerging knowledge about the effect of BoTx/A on afferent signalling mechanisms, suggests that a direct effect of BoTx/A on the afferent bladder innervation is responsible for the exceptional efficacy of the treatment. Concluding message The clinical response of patients with DO to BoTx/A may be partly the result of alterations in the afferent bladder mechanisms. FUNDING: Ipsen, UK and Allergan Ltd USA 151 Schurch B1, de Sèze M2, Denys P3, Chartier-Kastler E4, Ismael S5, Haab F6, Everaert K7, Keppenne V8, Plante P9, Perrouin-Verbe B10, Kumar C11, Fraczek S11

1. Univeritatsklinik Balgrist, 2. Hôpital Pellegrin, 3. Hôpital Raymond Poincaré, 4. Group Hospitalier Pitié-Salpétriè, 5. Hôpital de Rothschild, 6. Hôpital Tenon, 7. Ghent University Hospital, 8. CHU Sart Tilman, 9. Hôpital Rangueil, 10. CHU Nantes, 11. Allergan Ltd BOTULINUM TOXIN A (BOTOX®) IN NEUROGENIC URINARY INCONTINENCE: RESULTS FROM A MULTI-CENTRE RANDOMISED, CONTROLLED TRIAL Hypothesis / aims of study Recent evidence suggests that botulinum toxin type A (BOTOX®) may provide effective relief from neurogenic urinary incontinence in patients who have failed on oral anticholinergic therapy (1,2). This first placebo-controlled study aimed to show the safety and efficacy of two different doses of BOTOX® for the management of urinary incontinence caused by neurogenic detrusor overactivity. Study design, materials and methods This double-blind, multi-centre, randomised, placebo-controlled study was conducted in 59 patients (53 spinal cord injury; 6 multiple sclerosis) with urinary incontinence caused by neurogenic detrusor overactivity requiring clean intermittent self-catheterisation, who had failed on oral anticholinergic therapy. Following a 2-week screening period, each patient was randomised to receive a single masked treatment of BOTOX® (200U or 300U) or placebo at Day 0. Cystoscopic guidance was used to deliver the treatment as thirty injections, each of 1 ml, evenly over the detrusor muscle, avoiding the trigone. Patients were assessed during follow-up visits at weeks 2, 6, 12, 18 and 24. Changes in frequency of urinary incontinence episodes were monitored via patient bladder diary over the 24-week study period. Key urodynamic assessments (maximum cystometric capacity (MCC), reflex detrusor volume (RDV)) and maximum detrusor pressure during bladder contraction (MDP) were used to provide objective measures of treatment effect on bladder function at weeks 2, 6 and 24. Impact of treatment on quality of life parameters was assessed using the Incontinence Quality of Life questionnaire (I-QoL). The study was conducted in accordance with Independent Ethics Committee Regulations and in compliance with Good Clinical Practice and the Declaration of Helsinki, at 8 centres across Belgium, France and Switzerland.


Results Significant reductions compared to baseline (p≤0.05) in number of incontinence episodes were observed within both BOTOX® groups, but not within the placebo group. Mean reductions ranged from 32-54% and 42-58% in the 200U and 300U BOTOX® groups, respectively. Twenty-nine subjects experienced at least one week with no incontinence episodes; 83% of these subjects were in the BOTOX® treatment groups. Effects were apparent by the first assessment (week 2) and were maintained throughout the study period. Improvements in bladder function were also observed using the urodynamic assessments within both BOTOX® groups. Significant increases (p≤0.020) in mean MCC values and significant decreases (p≤0.023) in MDP values from baseline were apparent at all post-treatment timepoints. No such changes were observed with placebo treatment. Twenty-three subjects experienced no RDV for at least 1 follow-up visit; 91% of these subjects were in one of the BOTOX®-treated groups. For subjects who did have a post-treatment RDV, significant increases (p≤0.021) from baseline were apparent at week 6 (300U BOTOX®) and week 24 (200U BOTOX®). Robust improvements (p≤0.002) in mean change in total I-QoL score from baseline were recorded at all timepoints in BOTOX®-treated subjects throughout the 24 week study period. Incidence of adverse events was not significantly different between treatment groups, and no event was considered related to study drug. No cases of autonomic dysreflexia or systemic events were seen. Interpretation of results These results show rapid and sustained reduction in episodes of urinary incontinence following treatment with 200U and 300U BOTOX® in patients with neurogenic detrusor overactivity. Improvements in bladder function were evidenced by the urodynamic evaluations, which show an increased ability of the bladder to hold and retain urine following BOTOX® treatment and a reduced risk of vesicoureteric reflux, potentially preventing upper urinary tract deterioration and possible kidney damage. Improvements in signs and symptoms were appreciable by subjects as reflected in the higher I-QoL scores observed throughout the 24-week study period. No clear difference in clinical effect was apparent between the two BOTOX® doses. Concluding message This first controlled study demonstrates that treatment with a single dose of botulinum toxin type A (BOTOX®) combines rapid and sustained efficacy with a low incidence of side effects and represents a valuable option for managing urinary incontinence caused by neurogenic detrusor overactivity. The impact of dose on duration of action requires further evaluation. References

1. Schurch B, Stöhrer M, Kramer G, Schmid DM, Gaul G, Hauri D. Botulinum-A toxin for treating detrusor hyperreflexia in spinal cord injured patients: a new alternative to anticholinergic drugs? Preliminary results. J Urol 2000;164(3):692-697.

2. Reitz A, von Tobel J, Stöhrer M, et al. European experience of 200 cases treated with botulinum-A toxin injections into the detrusor muscle for neurogenic incontinence. Eur Urol (Suppl 2) 2003:140

FUNDING: Allergan Ltd

ICS and IUGA 2004

Author Index AAbramov Y 8, 9, 29, 90, 114 Abrams K 63 Abrams P 1, 3, 13, 15, 48, 60 Achtari C 86 Adams B 151 Adekanmi O 149 Adem A 36 Adorisio O 99 Ahmed I 36 Akhter S 97 Albo M 16 Al-Haj M 36 Al-Hayek S 13 Almeida F 57, 108, 112 Almeida F G 57, 108 Anand P 150 Anders K 92 Andrews V 33, 110 Apostolidis A 150 Approval Study Group P 54 Araki I 75 Arap S 101 Arce C 94 Arold G 140 Arruda H 132 Artibani W 126 Arya L 71 Assassa P 91 Assassa R P 63 Avelino A 81 Avery K 1, 3 B Badger W 41 Baessler K 2, 25 Ballario R 126 Balmforth J 34, 59, 92, 111 Balmforth J R 34, 111 Barry C 67 Barry C L 65 Bartolome V 61 Baskett T 7 Bast A 79 Battaglino G F 107 Battistutta D 2 Beaumont J L 114 Belal M 15 Bennett M 19 Beppu M 75 Bergamin L 42 Bernasconi F 66 Berse M 143 Beseghi U 107 Besson G 51, 137 Bianchi-Demicheli F 32 Bidmead J 92, 111 Biering-Sørensen F 55 Bini V 62 Birch C 24 Birder L 42, 109 Biscotto S 62 Bishop R 149 Bisseling T 23, 123 Bjarkam C R 84 Blackwell L 38, 88, 89, 94 Blake C 15 Bloembergen H 4, 98 Bonnet P 22

Bosch R 52 Botros S 8, 9, 29, 90 Bottin A 35 Boulanger S 27 Boulvain M 32 Bréart G 118 Briggs C 86 Brooks R 100 Brown J S 115 Brubaker L 18, 47, 87, 115 Bruenjes R 143 Brusa L 83, 85 Bruschini H 57, 108, 112, 131, 132, 147 Buckley M F 6 Buffa P 107 Bump R 121 Burcher E 40 C Capitanucci M L 99, 107 Cardozo L 34, 59, 92, 111, 141 Carey M 12 Carne C 26 Catarin M 131, 132 Cavalcanti G 131, 132 Cedenho A 57 Cervigni M 129 Chadwick M 1 Chaliha C 17, 139 Chancellor M 39 Chandranath S 36 Chapple C 63, 142 Charrua A 81 Chartier-Kastler E 151 Cheater F 63 Chichester P 41 Chinen Y 82 Claerhout F 27, 64 Clarke B 31 Clemons J 71 Cline K 144 Corstiaans A 67 Costantini E 62 Cottenden A 100 Coyne K 3, 95 Cropper M 25 Cruz C 81 Cruz F 81 Culligan P 38, 94 Curti P P 126 D Dallosso H 116 Dalmose A 84 Dalmose A L 84 Dambros M 79 D'amico A 83, 85, 126 Dasgupta J 45 Dasgupta P 150 Davila G W 28 Davila W 21 De Gennaro M 99, 107 De Groat W 39, 42, 109 De Jongh R 79 De Leval J 22 De Ridder D 27, 64 De Sèze M 151

ICS and IUGA 2004

Denys P 151 Deprest J 27, 64 Di Ciommo V 99 Di Lorenzo F 107 Diefenbach K 140 Dietz H 127 Dietz H P 31, 65, 67 Dimitriadis G 135 Dixon A 92 Djurhuus J C 84 Doi T 43 Donaldson M 116 Donovan J 1 Dorey D G 53 Dorey G 53 Dostonova A 139 Drahoradova P 68 Drinnan M 14, 15, 58 Drogendijk T 141 Drutz H 138 Du S 75 Dubbelman Y D 52 Duckett J 69 Dunn C 53 Dupont M 21 Dwyer P 86 E Eldridge A 31 Elinoff V 95 Elkadry E 87 Elliott R 45 Enck P 35 Epperly M 109 Evans R 148 Everaert K 151 Ewings P 53 F Fader M 100 Faltin D 32 Farrell K 7 Farrell S 7 Feneley R 53 Féra P 112 Fernando R 11 Finazzi Agro E 83, 85 Fitzgerald M 16 Fitzgerald M P 18, 115 Fjorback M V 55 Floris L 32 Foote A 26 For The Rrisk Study Group. . 115 For The Solifenacin Study Group 141 Forrest J 148 Forward M 19 Fowler C J 150 Fraczek S 151 Franco A V 24 Freeman R 149 Freire M 57 Fritel X 118 Frumkin L 148 Furuno T 104 Fynes M 24 G Galloway S 20 Gandhi S 8, 9, 29, 90, 114 Gard G 124 Gattei U 66

Giuliano L 131 Gladman M 34 Glashan R 112 Godwin A 133 Goh J 12, 19, 20, 97 Gokalp A 78 Goldberg K 144 Goldberg R 8, 29, 90 Goldberg R P 9, 114 Golubkov N 70 Gonzales S R 112 Gordon A 93 Grace M 31 Graham C 94 Gramatté T 143 Greenberger J 109 Griffiths C 14, 15, 58 Griffiths D 42 Groen J 52 Guerette N 28 H Haab F 151 Hagiwara A 72 Halaska M 68 Hannestad Y S 119 Hansen J 55 Harding C 14, 15, 58 Harris R 144 Harrison S 91 Haselmann J 140 Hashim H 60 Hashimoto T 43 Hattori T 37 Hayashi F 42 Hayashi Y 109 Heintz P 23, 96, 123 Heit M 38, 88, 89, 94 Henderson M 5 Hermieu J 137 Hessdoerfer E 143 Hextall A 111 Hill S 145 Hinninghofen H 35 Hirahara N 72 Hirani K 139 Hjalmas K 105 Hlasenska J 68 Hoey M 92 Hosoi T 74 Hoyte L 47 Huang Foen Chung J 136 Hunsicker K 133 Hunskaar S 117, 119 Hwang T 50 I Igarasi T 76 Iizuka H 44 Ikeda M 80 Ikegaki I 77 Inadome A 73 Inoue K 102 Irion O 32 Ishihama H 80 Ishihara Y 43 Ismael S 151 Ito T 37 Itoh T 72 Iwashita H 73 Iwata M 43

ICS and IUGA 2004

J Jacquetin B 113 Jain S 69 Jakab M 47 Jensen R 124 Jones P 11 Joo K 30 Juenemann K 143 Juliano L 132 Jünemann K P 105 K Kajiwara M 102 Kakizaki H 104 Kalivas K 135 Kamiyama M 75 Kanai A 42, 109 Karantanis E 122 Karram M 21 Kato M 102 Katsikas V 135 Kawatani M 77, 80 Kelly S 88, 89 Kelvin B 111 Kenton K 18, 87 Keppenne V 151 Kettle C 11 Khoo S K 20 Khullar V 17, 139, 145 Kihara K 39 Kim J 30 Kim J C 50 Kim K 103 Kim K M 103 Kim T 30 Kimura R 46 Kinchen K 121 Kitahara S 44, 125 Knoll L D 21 Koch V 101 Kodama M 76 Koduri S 114 Kohli N 21 Kohri K 49 Kojima Y 49 Kokubun S 76 Komoto I 46 Komur O 78 Kopp Z 3 Kracochansky M 101 Kramer G 105 Krause H 19, 20, 97 Kumar C 151 Kurihara M 102 Kwon C 29, 114 L Lamba A 139 Lattimer M 145 Lee S W 103 Leite K 108 Lelis M A 112 Lemack G 16 Levin R 41 Lewis J 61 Lim K 30 Lim Y N 67 Lind L 21 Liu L 40 Liu M 35 Liu Z 37

Lovatsis D 138 Lowndes C 26 Lundegaard Christensen T 146 M Macaulay M 100 Madersbacher H 143 Magatti F 66 Mahajan S 18, 87 Maher C 2, 25 Mansfield K J 40 Mantle J 111 Manzano G 131, 132 Margolis M 95 Marschall-Kehrel A 105 Martan A 68 Martin J 63 Masata J 68 Masuda H 39 Masunaga K 73 Matsuda Y 77 Matthews R 116 Mattiasson A 48, 146 Mattos Jr. D 147 Matuoka T 74 Mcdermott S 16 Mcgrother C 91, 116 Mcintosh S 15 Mckenzie B 86 Mcmahon S B 81 Mearini L 62 Media S 55 Mellier G 113 Mensah-Brown E 36 Merletti R 35 Meschia M 66 Meyers S 109 Mian S 120 Miano R 83, 85 Mikami Y 75 Miki T 72 Miklos J 21 Miles T 121 Miller T 122 Miyamae K 73 Miyazato M 82 Mohr B 16 Momota Y 80 Moore K 122 Moore K H 6, 40 Moore R 21, 113 Morison M 5, 93 Moriya K 104 Morkved S 10 Morozumi M 82 Morris A R 6 Mosbaugh P 148 Mosiello G 99 Mueller E 18 Mullan G 6 Muller R 67 Murphy M 38, 94 Mürtz G 105 Myers D 71 N Nabha K 61 Nagabukuro H 43 Nager C 16 Nakai H 125 Nakamura T 72 Nakamura Y 77

ICS and IUGA 2004

Nakanishi K 44 Naseer O 36 Natale F 129 Nelson P 51, 137 Nickolov A 8, 9, 90 Nimura T 77 Nishijima S 82 Nobrega J 132 Nóbrega J A 131 Nogueira M D P 112 Nohr M 56 Nøhr M 55 Nonomura K 104 Novara G 126 Novi J 71 Nunes K 131, 132 O O'brien S 11 Ogawa Y 82 Ohkawa H 125 Okadome A 128 Oki T 46 O'neill S 2 Orazi C 99 Ostfeldt L 48, 146 Otani M 73 Otero M 32 Ozkurkcugil C 78 P Pajoncini C 129 Panhoca R 147 Parisi I 85 Park E Y 50 Park Y H 50 Parsons M 59, 92 Patel B 133 Patel M 36 Patrick D 121 Pavlikova M 68 Payne C 148 Perrouin-Verbe B 151 Pesce F 126 Petersen T 56 Peterson J 109 Petropoulos S 138 Petta F 83, 85 Pettersson L 100 Piault S 118 Pickard R 14, 15, 58 Pifarotti P 66 Piskunova E 70 Plante P 151 Popat R 150 Porena M 62 Potter J 120 Poulsen P B 146 Q Qatawneh A 25 R Radley S 11 Radopoulos D 135 Rahmanou P 17, 139 Ramsden P 14, 15, 58 Rane A 65, 67 Reul O 22 Rijkhoff N 56 Rijkhoff N J M 55

Ringa V 118 Rios L 147 Rizk D 36 Roberts R G 95 Robertson G 48 Robinson D 59, 92, 141 Robson W 14, 15, 58 Rociola W 62 Roots I 140 Roppolo J 42 Rortveit G 117 Rosa A A 57 Rosamilia A 86 Roscioli T 6 Rubilotta E 126 Rudy D 144 S Saadoun K 118 Sakakibara R 37, 44 Sakakura K 46 Salvesen K Å 10 Sand P 8, 29, 90 Sand P K 9, 114 Sangalli M 32 Sasaki S 49 Sato K 76 Sato R 125 Schingo P 99 Schluter P 25 Schneider E 101 Schoenmaker G 4, 98 Scholfield D 17 Schor N 108 Schraffordt S 23, 123 Schurch B 151 Schwantes U 140 Seo S I 50 Serels S 21 Shaw C 63 Shek K 127 Sherman W 8, 9, 29 Shimizu Y 72 Shinoura H 49 Shinozaki S 77 Shott S 47, 87 Sinkjær T 55 Sinkjaer T 56 Siroky M 61 Skillern L 17 Slack M 133 Slieker-Ten Hove M C P 4, 98 Sloane K 97 Speakman M 53 Srougi M 57, 108, 112, 131, 132, 147 Staines H 5, 93 Stanzione P 83, 85 Stone D 5 Subak L L 115 Suda S 125 Sugaya K 82 Sugimoto S 76 Sugiyama Y 73 Sullivan F 5 Sullivan M 61 Sultan A 11, 33, 110 Summers K 121 Sutton A 63 Suzuki K 72, 130 Suzuki T 125 Svabik K 68 Swinkels A 53

ICS and IUGA 2004

T Tahaka M 128 Tahara H 128 Tai C 42 Takeda M 75 Takimoto Y 76 Tanaka H 104 Tangen T 146 Tanoue A 77 Tappin D 5 Taylor J 91 Thakar R 33, 110 Thom D 115 Thomas A 13 Thomas M 92 Thompson J 116 Tibaek S 124 Timoshin N 141 Tincello D 45 Tjandra J 12 Tracey M 133 Trigo Rocha F 101 Tsujimoto G 49, 77 Tubaro A 99 Turner D 63 Turuya Y 74 U Uchiyama T 37, 44 Ueda S 73 Ukimura O 72 Unamba-Oparah I 143 Ushijima S 72 Usui A 102 Usui T 102 V Valentini F 51, 137 Van Brummen P 96 Van Den Eeden S K 115 Van Den Homberg U 54 Van Der Vaart H 96 Van Kerrebroeck P 48, 54, 79 Van Koeveringe G 79 Van Mastrigt R 136 Van Voskuilen A 54 Varnoux N 118 Vasilakakis G 135 Vaux K J 40 Verbeken E 64 Verleyen P 27 Vermandel A 106 Vervest H 23, 123 Vieille J 32 Vierhout M 4, 98 Viganò R 66 Visco A 134 Voss Fjorback M 56 W Wada Y 76 Wagg A 120 Walters M 21 Waltregny D 22 Wassel Fyr C 115 Waterfield A 149 Waterfield M 149 Weil A 32 Weir J 129 Whitbeck C 41 Williams K 63

Williams M 92 Williams N 34 Williams R 20 Wilson P 5 Wilson P D 65 Winkler H A 21 Wollny A 140 Wu H 42 Wyndaele J 106 Y Yalcin I 121 Yalla S 61 Yamada S 46 Yamaguchi O 74, 130 Yamamoto T 37 Yamanishi T 37, 44, 125 Yamashita T 125 Yasuda K 44, 125 Yiangou Y 150 Yokota T 74 Yoshida K 44, 46 Yoshida M 73 Yoshimura N 39 Yoshimura Y 130 Yosida T 76 Z Zajicek J 149 Zeidel M 109 Ziegler C 38 Zimmern P 16, 137 Zougas K 135 Zuccalà A 83 Zyczynski T 3, 95

Documents

Joint Meeting of the International Continence Society and the International UroGynecological Association, 34rd Annual Meeting, Paris, France, 25th–27th August 2004