Adolf Lukanović, M.D., Ph.D.Mija Blaganje, M.D.,

Department of Gynecology and ObstetricsUniversity Medical Centre, Ljubljana, Slovenia

VI hrvatsko-slovenski simpozij o menopauzi i andropauzi, VI hrvatsko-slovenski simpozij o menopauzi i andropauzi, Hotel Neptun, Brijuni, 10.09.2011Hotel Neptun, Brijuni, 10.09.2011

Stress Urinary Incontinence Is the Most Common Type in Women Based on Literature Review

Hampel C, et al. Urology. 1997;50(suppl 6A):4-14.

Urinary incontinence affect at least one in every 4 women

Minassian VA, et al. Int J Gynecol Obstet 2003;82:327-38; Hunskaar S, et al. BJU Int 2004;93:324-30; Kinchen KS, et al. J Womens Health 2003;12:687-98; Hannestad YS, et al. J Clin Epidemiol 2000;53:1150-7

LITERATURE LITERATURE REVIEWSREVIEWS

LARGE-SCALE LARGE-SCALE SURVEYSSURVEYS

Urinary incontinence is prevalent, bothersome …but underreported: only 31 -

45% seek help

Hunskaar S, et al. BJU Int 2004;93:324-30; O’Donnell M, et al. Eur Urol 2005;47:385-92; Diokno AC, et al. Am J Manag Care 2004;10:69-78; Diokno AC, et al. J Urol 2003;170:507-11

Overall rate 31%

Prevalence of urinary incontinence increases with age

Hannestad YS, et al. J Clin Epidemiol 2000;53:1150-7; Hunskaar S, et al. BJU Int 2004;93:324-30

Next 20 years

18% increase of women > 75 years

38% increase of women > 80 years

Urinary incontinence:

11.6% > 65 years

8.5 % < 65 years

Koelbl et al 1987 Obstet Gynecol

Before application after application

6 o’clock 3 o’clock 9 o’clock

Teflon (Berg 1973, Politano 1974)

Purified bovine collagen (Contigen) (Shortliffe 1989)

Autologuos fatty tissue (Gonzales de Gariby 1989)

Silicon mikroimplants (Macroplastique) (Buckley 1992)

Mikrobaloons (Pycha 1998)

Copolymer of non-animal stabilised hyaluronic acid and dextranomer microspheres (Zuidex/Deflux) (Sternberg 1999)

Autologuos chondrocites (Bent 2000)

Pyrolitic carbon coated beads (Durasphere) (Calvosa 2000)

Acellular porcine collagen (Permacol) (Lightfoot 2001)

Polyacrylamid gel (97,5% water+2,5% cross-linked polyacrylamide) Bulkamid (Chancellor 2001)

Adjustable balloons (ACT) (Sauter 2002)

Urethral sphincter muscle augmented with Contura’s hydrogel (violet).

Picture taken 3½ months after injection.

Scattered macrophages appear in the gel, no surrounding foreign-body reaction - no fibrosis.

SYNTHETIC BULKING AGENTS IN URETHRAL TISSUESYNTHETIC BULKING AGENTS IN URETHRAL TISSUE

Bladder augmented with Bulkamid hydrogel (violet).

Picture taken 14 months after injection.

Gel appears as an irregular mass containing scattered macropgages which formed minute islands or a fine network within a homogeneous gel

SYNTHETIC BULKING AGENTS IN URETHRAL TISSUESYNTHETIC BULKING AGENTS IN URETHRAL TISSUE

The Bulkamid® Kit

Bulkamid ® Cystoscope2 prefilled 1 cc. Bulkamid® syringes

2 needles 23 G

1 irrigation set

1 optic 0˚

Light cable(not included in the kit)

Migration after 6 months

Pannek , J Urol 2001:166,1350

250-300 um

Lecce 2005

CULTIVATION AND CHARACTERISATION OF MYOBLASTS

Single myoblasts were manually collected with a micropipette, then clones of pure myoblasts with 100% of desmin positive muscle cells could be cultured.

MUSCLE BIOPSY ULTRASOUND GUIDED INJECTIONULTRASOUND GUIDED INJECTION

Skeletal muscle portion was obtained from a small open cut biopsy Skeletal muscle portion was obtained from a small open cut biopsy of the non–dominant biceps muscleof the non–dominant biceps muscle

Myoblast isolation and expansion was performed in GMP cerified Myoblast isolation and expansion was performed in GMP cerified cell-processing cell-processing laboratory Innovacell laboratory Innovacell Biotechnologie AG, Innsbruck, Austria

Autologus myoblast suspension was injected under transurethral ultrasound deviceAutologus myoblast suspension was injected under transurethral ultrasound device

THE IMPACT OF LOCALLY INJECTED STEM CELLS FOR THE TREATMENT OF FEMALE STRESS

URINARY INCONTINENCE

PROSPECTIVE RESEARCH TRIAL DEPARTEMENT OF GYNECOLOGY UCC LJUBLJANA

EXCLUSION CRITERIAEXCLUSION CRITERIA

UUrge incontinencerge incontinence

Descensus or prolapsDescensus or prolaps

Any sign of inflamationAny sign of inflamation

Serious sistemic diseasesSerious sistemic diseases

Previous antiincontinence Previous antiincontinence surgerysurgery

INCLUSION CRITERIAINCLUSION CRITERIA

Urodinamic proven pure Urodinamic proven pure SUI (standard ICS protocol)SUI (standard ICS protocol)

Age 50-70Age 50-70

Normal US examinationNormal US examination

Normal status gyn.Normal status gyn.

38 patients38 patients

UIS- amount of leaked urine measured semiquantitative

UIE- UI episodes count from a 3 day voiding diary

QOL- quality of life questionnaire

VAS- visual analog scale of the degree of suffering

PGI-I – modified patient global impression scale

Characteristics of patients treated with autologous myoblasts at baseline, at completion of preoperative ES cycle and at 6 weeks

postoperatively (Myoblasts + ES)

PreoperativePreoperative PostoperativePostoperative pp

BaselineBaseline ESES Myoblasts + ESMyoblasts + ES

No. of patientsNo. of patients 3838 3838 3737

UIEUIE 13 (4-41)13 (4-41) 12 (1-35)12 (1-35) 5 (0-33)5 (0-33) <0.0001<0.0001

UISUIS 24 (4-67)24 (4-67) 18.5 (2-49)18.5 (2-49) 5 (0-33)5 (0-33) <0.0001<0.0001

Stress test negativeStress test negative 00 11 2929 <0.0001<0.0001

PGI-I curedPGI-I cured improvedimproved unchanged unchanged

0000

3838

0077

3131

55292933

<0.0001<0.0001

I-QI-QOOLL 56.5 (28-92)56.5 (28-92) 63 (29-99)63 (29-99) 78 (41-105)78 (41-105) <0.0001<0.0001

VASVAS 8 (3-10)8 (3-10) 7 (4-10)7 (4-10) 3 (0-9)3 (0-9) <0.0001<0.0001

The numeric variables are presented as median values (range). The numeric variables are presented as median values (range). PP values are for ES values are for ES vsvs. Myoblasts + ES. Myoblasts + ES

IMPROVEMENT FROM BASELINE

VAS- visual analog scale of the degree of sufferingQOL- quality of life questionnaireUIE- 3-day bladder diaries for urinary incontinence episodesUIS- amount of leaked urine measured semiquantitative

The use of embrionic stem cells is limited due to unresolved medicolegal questions

When using stem cells of adult human being there are no medicolegal dilemas

TO WHAT EXTEND THE MYOBLASTS SHOULD PROLIFERATE ?

HOW TO PREVENT URETHRA OBSTRUCTION ?

WHAT WILL BE THE EFFECT OF URETHRAL HIPERMOBILITY ON THE SUCCESS OF STEM CELL THERAPY ?

DANGER OF MALIGNANT ALTERATION

ETHICAL ASPETSC AS THIS IS EXPERIMENTAL SURGERY

MEDICOLEGAL ASPECTS IN CASE OF FAILURE

COSTS

LEARNING CURVE FOR APLICATION

WILL STEM CELLS PRODUCE BETTER RESULTS THAT CURRENTLY AVAILABLE MEDICAL OR SURGICAL THERAPY?

WHAT MORBIDITY WILL IT CAUSE ?

STEM CELL THERAPY IS PROMISING. BUT BEFORE ADOPTING IT LET’S BE SURE IT WORKS

WHEN COMPARED TO CURRENTLY AVAILABLE PROCEDURES AND THAT IT WON’T HARM OUR PATIENTS.

WE ARE THE ONLY ONES WHO CAN PROTECT OUR PATIENTS

DON OSTERGARD, IUGA ANNUAL MEETING CANCUN 2007

URINARY INCONTINENCE should not be viewed as a normal part of aging

it should be viewed as treatable

Thank you for the attention