Assessment and Management of Female Stress Urinary Incontinence Saturday, May 17, 2008

6:00- 8:00 p.m.

COURSE 11 EC

FACULTY

Victor W. Nitti, M.D. Course Director

Harriette M. Scarpero, M.D.

American Urological Association Education and Research Inc.

2008 Annual Meeting, Orlando, FL May 17-22, 2008

Sponsored by: The American Urological Association Education and Research, Inc.

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2008 AUA Annual Meeting

11 EC Assessment and Management of Female Stress Urinary Incontinence 5/17/2008 6:00 - 8:00 p.m.

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Assessment and Management of Female Stress Urinary Incontinence:

State of the Art

Victor W. Nitti, MDDepartment of Urology

New York University School of Medicine

Harriette M. Scarpero, MDDepartment of Urology

Vanderbilt University School of Medicine

Evaluation of Stress Incontinence:What’s Essential and What is

Helpful?Victor W. Nitti

SUI: What Drives Treatment

• Nature, duration and severity of UI

• Effect of quality of life

• Risks and transient causes

• Prior therapy?

• Concomitant diseases– e.g. neurological disease, radical pelvic surgery

• Comorbidities

• Willingness to assume risk

AUA Female Stress Urinary Incontinence Clinical Guidelines - Standard

• Preoperative evaluation of women with symptom of SUI should comprise the 4 major components of:– History (impact on Q of L)

– Physical exam (objective demonstration of SUI)

– Urinalysis

– Other appropriate diagnostic studies designed to assess symptom causes

• Urethral hypermobility, ISD, detrusor dysfunction, frequency and severity of incontinence episodes, patient expectations from treatment

Leach et al: J Urol 1997;158:875

AUA Female Stress Urinary Incontinence Clinical Guidelines - Standard

• Patients should be informed of the available surgical alternatives– Estimated risks and benefits of each procedure

– Choice of treatment made by patient and surgeon taking into consideration patient preferences and experience and judgment of the surgeon

– Patients should be informed of complications and how they would be treated

Leach et al: J Urol 1997;158:875

• Purpose/Objectives: To establish a guideline for the treatment of stress urinary incontinence in two types of index patients:

– The otherwise healthy woman who has decided to seek surgical therapy for stress urinary incontinence ( only index patient used in first guidelines published in 1997)

– The otherwise healthy woman, who has decided to seek surgical therapy for stress urinary incontinence, and who also has concomitant pelvic organ prolapse

AUA Stress Urinary Incontinence Guidelines: Update 2008

Courtesy of Rodney Appell

• Inclusion Criteria– Surgical therapy for adult female stress urinary

incontinence.– Minimum follow up of 12 months.– Treatment available in the United States.– English Literature only.

• Exclusion Criteria– Surgical therapy that is deemed not current.– Male & peds pts; prolapse only patients

CriteriaProcedures Considered

• Slings– Multiple types

• Suspensions– Burch– Laparoscopic– Open Retropubic

• Bulking agents– Collagen

• Artificial urinary sphincter

Sling Procedures Considered– Autologous fascia with bone anchors

– Autologous fascia without bone anchors

– Autologous vaginal wall slings w/without bone anchors

– Autologous vaginal wall slings with bone anchors

– Cadaveric with bone anchors

– Cadaveric without bone anchors

– Cooper's ligament sling (all sling materials)

– Homologous tissue (dermis) with bone anchors

– Homologous tissue (dermis) without bone anchors

– Synthetic at bladder neck with bone anchors

– Synthetic at bladder neck without bone anchors

– Synthetic at midurethra

– Xenograft with bone anchors

– Xenograft without bone anchors

Methods

0

1000

2000

3000

4000

5000

6000

7000

8000

Literature search results Chosen for ExtractionArticles accepted Complications data only

Articles rejected

7,111

1,302437 155

865

Recommendations

• > 48 MONTHS:– Inadequate data to make statement; for example, we know

that > 1 million MUS done, but literature has data on only 80 patients

• 24 - 48 MONTHS:– Reaffirms data from 1997 Guidelines that Burch = Sling

• !RCT (Ward, Hilton)

• 697 Burches vs 715 slings

Observations

• Slings at the bladder neck have a higher rate of retention > 4 weeks post op or requiring surgery than slings at mid-urethra or suspensions

• De Novo Urge Post op– Burch & MUS – Similar (confidence intervals overlap)

• Unspecified urgency (urgency alone or with urge incontinence)– Data does not allow us to distinguish between procedures

Observations

• Mixed Incontinence– A small # of studies suggest that surgical repair of

the SUI component cures the urge component in approx 70% of cases

• Secondary procedures– Retreatment rates are not accurate

• Many authors left this out• Denominators not realistic or known• Incidence of complications/type of secondary procedure not clear

– Prolapse rates following SUI procedure – too variable to evaluate

• Prospective randomized controlled trials

• Consistency of diagnostic criteria

• Standardized outcome measures

• Follow up > 12 months

Recommendations

Evaluation

• Once the desire for treatment beyond conservative therapy is established what factors may be important in determining treatment and predicting outcome:– Urethral mobility

• Physical exam (visual)• Q-tip test• Radiographic determination

– Urodynamics– Voiding diary, pad testing

Urodynamics in SUI

• Value of urethral resistance testing– ALPP, MUCP

• Value of cystometry– 30-50% of women presenting for treatment of SUI

have mixed symptoms

– MUI patients tend to have more severe incontinence

• Value of evaluating voiding phase

SISTEr Trial;Urinary Incontinence Treatment Network (UITN)

• Randomized trial comparing the efficacy of Burch vs. PV in 655 selected women with pure or predominate SUI for at least 3 months (9 sites through NIH/NIDDK)

– < 12 micturitions/day

– Positive standardized stress test (volume <300 ml)

– MCC >200 ml

– PVR <150 ml (unless POP grade II-IV)

– Unobstructed voiding• Qmax > 12 mL/s,

• PVR <150 mL

• pdetQmax < 50 cm H2OAlbo, et al NEJM 2007;356:2143-55UITN Urology 2005;66:2113-2117

UDS in the SISTEr Trial

• 2-fold greater odds for overall success for women with urodynamic SUI vs. those without– No USUI was about 10%– After controlling for predictors of success in the

multivariable model this was nearlystatistically significant– No difference in stress specific cures

• VLPP did not affect overall or stress specific outcomes

• Presence of DO did not affect overall or stress specific outcomes

• “Impact of UDS on surgical outcomes needs further investigation”

Nager, et al J Urol 2008;179:1470-1474

UDS for Patients withMixed Incontinence

• Several reports show that for patients with mixed symptoms and no DO on CMG cure for stress andurge incontinence is high (72-87% cure)– PV sling / Burch

• Osman BJU International 2003; 92:964

– PV Sling• Chou et al J Urol 2003; 170: 494

– TVT• Rezapour and Ulmstem Int Urogynecol J 2001 (suppl 2)

S15-18

UDS Predicting Outcome For Surgery For MUI

Although there is lack of controlled studies available data suggests that:

1. Patients with MUI and no DO have better outcomes than those with DO with respect overall continence and resolution of UUI

2. Patients with MUI and no DO on CMG have outcomes similar to those with pure SUI

3. The type and degree of DO may also play a role in outcome

Does this affect treatment or counseling?

Does UDS Predict Post-Op Voiding Dysfunction After PVS?

• Miller at al: J Urol 2003;169:2234– No contraction 19% retention, 18% delayed voiding– Normal contraction, 0% retention 11.1% delayed voiding– Valsalva void had no effect

• Iglesia et al: Obstet Gynecol 1998;91:577– Objective failure = 54% for Valsalva vs. 17% for non-

Valsalva voiders (p=.011)– Median post-op catheterization = 23 days for Valsalva vs.

14 days for non-Valsalva voiders (p=.049)

• McLennan et al, Obstet Gynecol 1998;92:608– Neither pdet nor Valsalva voiding predicted return to

normal voiding or retention

}

}Yes

}No

SISTEr Trial:Preop UDS Does Not Predict Post op Voiding Dysfunction

• Voiding dysfunction (VD) defined as:– Catheterization for > 6 weeks– Surgical takedown

• 57/655 (8.7) developed VD– 8 Burch– 49 PVS

• No preoperative UDS finding was associated with increased risk of VD– Non-intubated and pressure-flow study Qmax– PVR– Change in pves or padb at Qmax– Change in pdet at Qmax Lemack, et al Abstract Neurourol Urodyn 2008;27(2):123

Presented at SUFU, 2008

Summary of UDS for SUI

Most studies that recommend against the routine use of UDS prior to SUI surgery do not include women with significant urge component

• Presence and characteristics of DO has been shown to predict outcomes for patients with mixed symptoms in some studies

• Data on pre op voiding parameters are contradictory– Not much for midurethral synthetic slings

Highest Yield for Urodynamics In SUI

• Simpler diagnostic tests are insufficient

• Mixed incontinence

• Empiric treatments unsuccessful

• Cannot demonstrate UI clinically

• Prior incontinence or radical pelvic surgery

• Pelvic radiation

• Known or suspected neurological disease

• Significant voiding symptoms

• Elevated PVR

Urodynamics Before Non-Conservative Treatment of SUI

• Do UDS if:– Results will help counsel the patient

– Unsure of diagnosis

– There is a history of voiding symptoms or elevated PVR

– Determination of ALPP or other UDS parameters will affect choice of surgery

• Do not do UDS if:– You are going to treat the patient the same way no matter

what the findings and UDS will not influence how you council the patient

What Is ISD?

• Concept introduced by McGuire and colleagues– Retrospective analysis of the results of anti-incontinence

surgery

– Some women who multiple retropubic operations had a deficient sphincteric mechanism characterized by an open bladder neck and proximal urethra at rest with minimal or no urethral descent during stress

• ISD denotes an intrinsic malfunction of the urethral sphincter, regardless of its anatomic position

Classification of Stress IncontinenceBlaivas and Olsson, J Urol 139:737, 1988

• Type 0 - typical history for SUI, hypermobility, but no incontinence demonstrated

• Type I - bladder neck closed at rest, minimal hypermobility (<2cm), incontinence with increased abdominal pressure

• Type IIA - Vesical neck closed and above inferior margin of symphysis at rest. During stress vesical neck and proximal urethra open and there is rotational descent with incontinence

• Type IIB - Vesical neck is closed and situated at or below inferior margin of symphysis at rest. During stress +/- added descent, but the urethra opens and incontinence ensues

• Type III - Vesical neck and proximal urethra open at rest. Obvious urinary leakage with gravity or minimal abdominal pressure

Pathophysiology of SUI

ISDONLY

ISD

UrethralHypermobility

Urethral Hypermobility + ISD

All women with SUI have some degree of ISD because hypermobility often exists without SUI

UDS Measures of ISD

• Abdominal Leak Point Pressure (ALPP)– Valsalva leak point pressure (VLPP)

• Maximum Urethral Closure Pressure (MUCP)

Leakage at arrow = ALPP = 109cmH2O

ALPP - Intravesical pressure at which urine leakageoccurs due to increased abdominal pressure in theabsence of a detrusor contraction

Urethral Pressure MeasurementsUPP –intraluminal pressure along length of urethra

• Maximal urethral pressure (MUP)– Maximum pressure of the

measured profile

• Maximum urethral closure pressure (MUCP)– Maximum difference between

the urethral and intravesical pressures

• Functional profile length– Length of the urethra along

which the urethral pressure exceeds the intravesical pressure in women

Urethral pressure profile

Gravitational IncontinenceALPP = 34 cmH2OOpen bladder neckType 3 SUI

23 year old female with “total and unaware incontinence”

Urodynamic Stress Incontinencewith hypermobility and ALPP = 109 cmH2OHow much ISD?

What Is ISD?

• Portion or component of stress incontinence not caused by a support defect (urethral hypermobility)– Lack of coaptation

– Deficiency of urethral musculature

– Deficiency of submucosal layer

– Neurological injury

ISD What Does it Mean?

• Can the presence or degree of ISD be accurately determined or quantified in the face of urethral mobility?

• Not the overall competency of the urethra, but the component that is independent of urethral mobility?

What is ISD and How is it Defined In the Face of Urethral Hypermobility?

• SUI with lack of urethral mobility?

• ALPP < 60 cmH2O?

• ALPP < 90-100 cmH2O?

• MUCP < 20 cmH2O?

• Bump et al (1997) – correlation but lack of concordance between MUCP and ALPP

• What does “ISD” mean when choosing a treatment for SUI?

Comparing Measures of Sphincter Function

• ALPP• MUCP

• Only ALPP requires the patient to actually have SUI in order to measure

• Which urethra is “worse”?– Continent with MUCP of 40 cmH2O– Incontinent with MUCP of 45 cmH2O

Sphincter Function

• We have traditional defined sphincter function in terms of a pressure measurement

• What about in volume of urine lost?

• Which urethra is “worse”?– ALPP = 65 cmH2O, 1 ml of urine loss

– ALPP = 95 cmH2O, 30 ml urine lost

MUCP and ISDWhere Do The Numbers Come From?

• Retrospective determination that a preoperative MUCP <20 cmH2O resulted in higher surgical failure rates 1

• These patients represented a specific subtype of SUI, type III

• In 1992 the term was redefined as ISD 2

1. McGuire EJ. Urodynamic findings in patients after failure of stress incontinence operations. Prog Clin Biol Res 1981; 78:351–354.

2. Urinary Incontinence Guideline Panel. Urinary incontinence in adults: clinicalpractice guideline. AHCPR publication no. 92-0038. Rockville, MD: Agencyfor Health Care Policy and Research, Public Health and Human Services;1992.

ALPP and ISDWhere Do The Numbers Come From?

• MUCP and ALPP measured in 125 women with SUI

• ALPP <60 cmH2O– All had high grade (3) incontinence (81% continuous leakage)

– 75% fixed urethra

• ALPP 60-89 cmH2O– 80% pronounced type II urethral hypermobility and grade 2-3

incontinence

• ALPP >90 cmH2O– Lesser grades of incontinence and minimal to gross

hypermobility (type I or II)

• ALPP unrelated to MUCPMcGuire, et al J Urol 1993; 150:1452-1455

The Inference

• ALPP < 60 cmH2O = ISD• ALPP 60 - 90 cmH2O = equivocal, a component of

ISD• ALPP > 90-100 cmH2O little or no ISD

• But if no hypermobility, SUI must be caused by ISD

• Current technology does not permit a method to distinguish between ISD and hypermobility

Urethral Hypermobility vs. ISDFleischmann et al J Urol 169:999, 2003

• No correlation of ALPP with hypermobility:– ALPP < 60 24% hypermobile– ALPP 60-90 31% hypermobile– ALPP > 90 41% hypermobile

• No correlation of hypermobility or ALPP with number of incontinence episodes or pad weight

• ISD and hypermobility can coexist but do not define discrete classes of patients– Use parameters to characterize not classify

UPP – ICS Standardisation SubcommitteeLose, et al Neurourol Urodyn 21:258-260, 2002

• Clinical utility of urethral pressure measurement is unclear

• There are no urethral pressure measurements that:– Discriminate urethral incompetence from other disorders– Provide a measure of the severity of the condition– Provide a reliable indicator to surgical success and return to

normal after successful intervention

• Urethral pressure measurement is still first and foremost a research tool

Ultimately What Do We ReallyNeed To Know?

• Is there a measure of “ISD” (or urethral function) that predicts outcome of intervention?

• More importantly is there a measure of ISD that can help to select a procedure?

• In 2008 that means outcomes for midurethral slings and different approaches and bulking agents

• May also apply to conservative and other minimally invasive therapies

Measuring The Measures

• Both ALPP and UPP lack standardization in the literature and are used indiscriminately

• Reports on outcomes of surgery based ALPP and UPP (MUCP) are variable– Few study separate out urethral mobility

component

– Will discuss more later

Stress Incontinence and POP

• POP and SUI are associated conditions– May coexist– POP may be “protective” of SUI as it can cause kinking of

the urethra or and thus can “mask” SUI.

• Repair of POP in clinically continent women has been shown to result in post-op SUI in 11-22%– -Stanton, 1982; Borstad, Torkel, 1989

• Simultaneous anti-incontinence procedure at the time of POP repair is a topic of much interest.

Stress Incontinence and POP

• Clinical SUI – patient complains of the symptom

• Urodynamic SUI – demonstrated on a UDS study

• Occult SUI – demonstrated only when the prolapse is reduced

No pessary Pessary

Clinically andUDS continent

UDSincontinent

OCCULTSUI

With High Grade POPWhen There is No Clinical SUI

• Some endorse simultaneous prophylactic anti-incontinence procedure.– Brubaker et al 2006 (CARE trial), Twiss et al 2007

• Some recommend evaluating for occult SUI prior to POP repair and selectively performing an anti-incontinence procedure.– Chaikin et al 2000, Ghoniem et al 1994, Liang et al 2004

• Others believe that routine performance of an anti-incontinence procedure in continent women may add unnecessary morbidity. – de Tayrac et al 2004, DeLancey 1996, Zimmern 1998

Treatment of Clinical SUI at the Time of POP repair

• Procedures found to be effective for SUI are also effective combined with POP repair– Midurethral synthetic slings (Groutz 2004)

– Pubovaginal slings (Barnes, et al 2002)

– Burch procedures (Brubaker, et al 2006)

Occult SUI2 prospective controlled studies with TVT• de Tayrac et al, 2004

– 19 patients (11 TVT, 8 no TVT)

– No post op SUI in TVT group, 12.5% in no TVT group (No difference)

– Higher post op voiding dysfunction in TVT group

• Liang et al, 2004– Hysterectomy with A/P repair + TVT vs. no TVT

– OSUI diagnosed by pessary test

– TVT – 10% subjective SUI, 0% objective SUI

– No TVT – 64.7 % subjective SUI, 53% objective SUI

AUGS CARE TrialBrubaker et al NEJM 2006;354(15):1557-1566

• 322 patients undergoing abdominal sacrocolpopexy randomized to Burch (157) vs. no Burch (165)

• 36% of women in each group had OSUI• SUI by one or more criteria (symptoms, stress

testing, treatment) at 3 months post op– No Burch 44.1% (24.5% bothersome)– Burch 23.6% (6.1% bothersome)

• Significant postop SUI even if no OSUI– No Burch 38.2%– Burch 20.8% POSUI

• No increase in retention or LUTS with Burch

UDS Protocol

• If urodynamic or occult SUI - simultaneous MUSS– Exception for women at high risk for retention

(Impaired contractility or retention preop)

• If no urodynamic, or occult incontinence then no anti-incontinence procedure

Ballert, et al AUA 2008

UDS Protocol

• Looked at the risk of needing a second procedure to correct something caused by the initial procedure– Risk of intervention for post op SUI is the risk of

having a secondary sling or bulking agent

– Risk of intervention for obstruction from a sling is the risk of needing a sling loosening, cutting or urethrolysis

Ballert, et al AUA 2008

105Women

50 Clinical SUI

55No Clinical SUI

31UDS/OSUI

40 UDS/OSUI

10No

UDS/OSUI

MUSS NO MUSS

24No

UDS/OSUI

MUSS NO MUSS

Ballert, et alAUA, 2008

All Patients withStage 3 or 4 Prolapse

105women

50 Clinical

SUI

55 NoClinical SUI

31UDS/OSUI

MUSS

40 UDS/OSUI

MUSS

10 No UDS/OSUINO MUSS

3 (7.5%) MUSS

takedown

3 (30%)intervention

SUI

24 NoUDS/OSUINo MUSS

3 (9.7%)MUSS takedown

1 (3.2%)intervention SUI

2 (8.3%) intervention

SUI

Ballert, et alAUA, 2008

Results

• ROI due to obstruction after MUSS placement –8.5%

• ROI for SUI in patients with no clinical, UDS or occult SUI and no MUSS - 8.3%

• ROI for SUI in patients with clinical SUI, but no MUSS - 30%

• Overall ROI for SUI if MUSS placed - 1.4%

What We Do

• For a transvaginal POP repair:– If clinical, urodynamic or occult SUI perform

simultaneous anti-incontinence procedure• Exception for women at high risk for retention

– Some elderly, impaired contractility, retention preop

– If no clinical or demonstrable SUI, no anti-incontinence procedure

• Up to surgeon to discuss pros and cons of a “completely “prophylactic” procedure

• For an abdominal sacrocolpopexy consider and anti-incontinence procedure for most women

Conservative Treatments for SUI: Objective Review of The Data

Victor W. Nitti

Conservative Therapies For Incontinence

Behavioral Modification

Education

Delayed Voiding

Timed VoidingReinforcement

Pelvic Floor Rehabilitation Fluid

Restriction

Dietary &LifestyleChanges

Pelvic Floor Rehabilitation

• PFMT (initial description by Kegel in 1948)

• Vaginal cones

• Biofeedback

• Electrical stimulation

• Magnetic stimulation

PFMT Rationale

• Stress Incontinence– Strengthen pelvic floor musculature and thus urethral

support– Regain the normal unconscious activation of pelvic floor

muscles during increases in abdominal pressure– Learn voluntary activation of a compensatory mechanism

• Urge Incontinence– Contraction of striated paraurethral musculature causes

reflex inhibition of detrusor contractions– Improved reflex inhibition of detrusor contractions

secondary to stronger pelvic floor muscles

PFMT

• Protocols vary in description of:– Frequency and number of contractions– Length of hold and relax periods– Strength and endurance periods– Self vs. instructor taught

• Level of evidence and quality of studies found to be low in a recent meta analaysis (Latthe BJOG 2008;115:435-44

• Prior to beginning PFMT all women should be assessed to make sure that they can do a voluntary pelvic floor muscle contraction

Assessing Pelvic Floor Rehabilitation

• Proceedings and recommendations from the 3rd

International Consultation on Incontinence (ICI) provides a comprehensive review of the literature and offers “guidelines”– Wilson, et al In: Abrams P et al. Incontinence. 3rd

International Consultation on Incontinence; Monaco, June 26-29, 2004. 3rd Edition 2005

ICI Recommendation

• Based on extrapolation of data from exercise science literature PFMT programs should include:– 3 sets of 8-12 slow velocity maximum voluntary

PFM contractions

– Sustained for 6-8 seconds

– Preformed 3-4 times/week

– For at least 15-20 weeks

Pelvic Floor Muscle Training vs No Treatment, or Inactive Control Treatments, For

Urinary Incontinence in Women: Cochrane Review, 2006

• The Cochrane Incontinence Group Specialized Trials Register was searched (Dec 1, 2004)

• Randomized or quasi-randomized trials in women with stress, urge or mixed urinary incontinence – One arm of the trial included pelvic floor muscle training

(PFMT)– Another arm was a no treatment, placebo, sham, or other

inactive control

• PFMT was defined as a program of repeated voluntary pelvic floor muscle contractions taught and supervised by a health care professional

Hay-Smith, EJC, Dumoulin C, Reprinted Jan 2008

Cochrane Review 2006 Results

• Thirteen trials involving 714 women (375 PFMT, 339 controls) met the inclusion criteria, but only six trials (403 women) contributed data to the analysis– Most studies were at moderate to high risk of bias, based on

the trial reports

– There was considerable variation in interventions used, study populations, and outcome measures

• Women who did PFMT were more likely to report they were cured or improved than women who did not

• PFMT women also experienced about one fewer incontinence episodes per day

Hay-Smith, EJC, Dumoulin C, Reprinted Jan 2008

Cochrane Review 2006Authors’ Conclusions

• Review provides some support for the widespread recommendation that PFMT be included in first-line conservative management for women with stress, urge, or mixed, urinary incontinence

• Statistical heterogeneity reflecting variation in incontinence type, training, and outcome measurement made interpretation difficult

• The treatment effect might be greater in younger women (in their 40’s and 50’s) with stress urinary incontinence alone, who participate in a supervised PFMT program for at least three months, but these and other uncertainties require testing in further trials

Hay-Smith, EJC, Dumoulin C, Reprinted Jan 2008

Biofeedback

• Monitoring instruments to detect and display physiologic events or conditions– Vaginal or anal probes

– Surface electrodes

– Visual or auditory display

– Intravaginal resistance devices• Pressure-filled vaginal probe

Biofeedback Efficacy

• Level 1 evidence that BF-assisted PFMT is no more effective than PFMT alone for women with stress and mixed incontinence (3rd ICI)– Also supported by review of Latthe BJOG, 2008

• Clinicians may find occasions when BF is a useful adjunct to treatment for purpose of teaching, motivation, compliance, etc

• Best use would appear to be in women who cannot identify PFM– Large scale RTC’s needed to study this

Electrical Stimulation3rd ICI

• Lack of consistency in programs used to treat women with SUI, UUI and MI

• Insufficient data to determine if ES is better than no treatment for women with USUI or DO

• No benefit to adding ES to PFMT, but further investigation needed– Also supported by review of Latthe BJOG, 2008

Pharmacotherapy

• Alpha-adrenergic drugs– Inconsistent results, high AE’s

• Duloxetine 5-HT NE reuptake inhibitor– Available in Europe

– Withdrawn from FDA consideration for approval in US

– Pooled Analysis 52% reduction in median IEF vs. 33% for placebo (statistically significant)

– Available as Cymbalta, an depressant, in US

Estrogen For Incontinence

• HERS - estrogen + progestin (Grady, 2001)* – Daily oral estrogen + progestin associated with worsening incontinence

in older postmenopausal women with weekly incontinence

• WHI - estrogen +/- progestin (Hendrix, 2005)*– HRT was not beneficial in treating or preventing incontinence– HRT increased the risk of developing incontinence in women who did

not have incontinence at start of study– HRT worsened the characteristics of preexisting symptoms

• Hextal review of 87 studies (Maturitas 2002:36:83)– No help for SUI or UUI

• Estrogen no longer recommended as treatment or prevention of incontinence * Double-blind placebo controlled studies

Systematic Review: Randomized, Controlled Trials of Nonsurgical Treatments for Urinary

Incontinence in Women (NIH Conference)

• 96 RCT’s and 3 systematic reviews• Compared with regular care, pelvic floor muscle training with or

without bladder training resolved urinary incontinence– For PFME alone the effect size was inconsistent across studies

• Electrical stimulation failed to resolve urinary incontinence• Oral hormone administration increased rates of urinary

incontinence compared with placebo in most RCTs (1243 pts)• Transdermal or vaginal estrogen resulted in inconsistent

improvement of urinary incontinence• Adrenergic drugs did not resolve or improve urinary

incontinence• Duloxetine compared with placebo improved but did not resolve

urinary incontinence, with no significant dose–response association

Shamliyan, et al Ann Int Med 2008;148(6):1-15

Minimally Invasive Office Procedures for SUI

Harriette M. Scarpero

Bulking Agents as an Option

• Patient decisions on treatment are related to expectations and level of risk

• Although improvement more likely than cure, safety and lack of convalescence remains the main advantage

• No perfect agent, nothing yet proven superior

Collagen vs. SurgeryCorcos et al: Urology 2005;65:898-904

• Multicenter RTC comparing collagen to surgery (different operations done)

• Success rate 12 mos after collagen was lower than after surgery 53.1% vs 72.2%

• General and disease specific QOL score by validated instruments were similar in the two groups

• Satisfaction between therapeutic groups was not statistically significant

Indications for Bulking Agent in 2007

• Patient or surgeon preference• Severe comorbid disease• SUI in the face of late radiation effects• SUI after neobladder• Sling failure • SUI after pessary placement• MUI with significant detrusor overactivity

-bulking agent “tests” the effect of increased urethral

resistance prior to surgery

Complications of Bulking Agents

• Hematuria, pain• UTI• Transient voiding dysfunction or retention• Extrusion of material• Granulomatous reaction• Prolapse of urethral mucosa• Urethrovaginal fistula- rare in normal tissue

Bulking AgentsFDA Approved 2007

• Bovine Collagen Contigen®

• Pyrolytic Carbon Particles Durasphere™

• DMSO/ ethylene vinyl alcohol copolymer Tegress™

• Calcium hydroxylapatite Coaptite®

Under Investigation• Hyaluronic acid and dextranomer Zuidex™

• Silicone Macroparticles Macroplastique®

Should Bulking Agents be Limited to the Treatment of The Non-mobile Urethra

• Studies using collagen have show similar success in mobile vs non-mobile urethras– Herschorn, et al J Urol 1999; 156:1305– Corcos and Fournier, Urology 1999, 54:815– Bent et al, J Urol 2001, 166:1354 (multicenter)

• Registration studies for new agents have specific inclusion criteria– Low ALPP– Minimal urethral mobility

Bovine CollagenContigen

• Easy delivery• Antigenic phenomena 2-4%• Begins to degrade in 12 weeks• Repeat or booster injection needed• Durability of success without further injections

(Herschorn et al.: J. Urol.: 156: 1305, 1996)– 71% at 1 year– 58% at 2 years– 46% at 3 years

Collagen Results Summary

• Pooling data from all studies, short term(1 year) outcomes are approximately:– 25% cure

– 50% improved

– 25% failed

• With 1-3 initial injections

Durasphere

• Pyrolytic carbon coated zirconium oxide beads

• No antigenicity

• Tends to plug device– Likely extrusion of

carrier first as less viscous

– Less likely with newer formulation?

Durasphere OutcomesLightner, et al Urology 58:13, 2001

• 355 patients treated in a randomized trial of Durasphere (178) vs. Contigen (177)– 115 Durasphere patients followed >12 months

• Mean # of injections = 1.69 vs. 1.55 for Contigen

• 12 month outcomes Durasphere vs. Contigen: Patients followed 12 months from baseline:– ↓ pad wt. 27.9 vs. 26.4 gm– improved Stamey grade 66.1% vs. 65.8%– vol injected 7.55 vs 9.58 ml

• Durasphere had a 31% cure (from FDA submission)

Durasphere Vs. ContigenExtended Follow-up

Chrouser et al, J Urol. 171:1152-5, 2004

• 56 women treated with Durasphere compared to age matched women treated with Contigen– Telephone interview

• Tx initially effective in 63% of both• At 24 and 36 mos:

– Durasphere effective in 33% and 21%– Contigen effective in 19% and 9%

• At last follow-up ( 51 and 62 mos) 21% in the Durasphere group and 5% in the Contigen group felt tx was effective

Coaptite®Calcium Hydroxylapatite

• Supplied in 1cc syringes• Most applications are 1-

2 cc• Easy Injection• Standard

equipment, except 21 gauge needle

• No special storage• Non-allergic

Particle size 75-125 um

CaHC vs. Bovine Collagen

• Randomized trial of women with SUI secondary to ISD based on ALPP

• Non inferiority study• Efficacy was determined by improvement on the

Stamey Urinary Incontinence Scale– 0 dry– 1leakage with vigorous activity– 2 leakage with minimal stress– 3leakage regardless of activity or position

• Patients allowed up to 5 injection in the first 6 months

Mayer, et al Urology 2007;69:876-830

Coaptite vs Contigen:Results

• Improvement of >1 Stamey grade at 6 months– Coaptite - 74%

– Collagen – 71% p=0.57

• Improvement of >1 Stamey grade at 12 months– Coaptite - 63.4%

– Collagen – 57.0% p=0.34

• Intent to treat population (LOCF)– Coaptite - 58%

– Collagen – 51% p=0.24Mayer, et al Urology 2007;69:876-830

Coaptite vs Contigen:Results

• Cure rate at 12 months– Coaptite - 39%

– Collagen – 37% p=0.78

• 24 Hour Pad Weight Reduction of >50% - 12 months– Coaptite - 62% ITT 51%

– Collagen – 54% p=0.23 38% p=0.055

• Mean change pad weight at 6 and 12 months– Coaptite 19.5 g versus 17.2 g

– Collagen 19.3g versus 31.4 gMayer, et al Urology 2007;69:876-830

Coaptite vs Contigen:Number of Injections

• Mean # injections– Coaptite - 1.9

– Collagen - 2.0

• Only 1 injection– Coaptite - 38%

– Collagen - 26.1% p = 0.03

Mayer, et al Urology 2007;69:876-830

Stem Cells for SUI

• Aim of stem cell therapy is to replace, repair, or enhance the biological function of urethral sphincter

• Two types– Embryonic stem cells

– Adult stem cells

Autologous stem cells are obtained with a biopsy of tissue, the cells are dissociated and expanded in culture, and the expanded cells are implanted into the same host.

Furata et al Neurourol Urodyn 2007

Tissue Engineered Bulking Agents

• Multiple animal models• Chondrocytes• Detrusor myocytes

– Hypothesis: in native environment will retain their normal differentiation and fxn

• Primary myoblasts– Hypothesis: mass effect, ↑resistance, improve sphincter

function

• Autologous fibroblasts (bx from upper arm)– 85% of 130 patients initially continent (Abstract #328)

Stem Cells for Bulking Agents

• Muscle derived stem cells (MDSC)– Differentiate into myogenic and non-myogenic lines

• Skeletal derived satellite cells– Myogenic precursors with limited differential potential

• Chondrocytes– Arise from mesenchymal stem cells and have intrinsic

ability to produce extracellular matrix (ECM) and cartilage in vivo

• Adipose derived multipotent stem cells

Muscle Derived Stem Cells

• Uniquely different from fibroblasts and smooth muscle cells

• Fuse to form post-mitotic multinucleated myotubes– Limits persistent expansion and risk of obstruction

• Form myotubes and myofibers that become innervated into the host muscle– Serve as a bulking agent, but also may be physiologically

capable of improving urethral sphincter function.

Adipose Derived Stem Cells

• Have been shown to differentiate into adipogenic, myogenic, and osteogenic cells in the presence of lineage-specific induction factors

• ADSCs exhibited the functional ability to contract and relax in direct response to pharmacologic agents

Stem Cells and Incontinence

• Chancellor et al, Urology 2006

• Randomized, controlled comparison of MDCs and fibroblasts for restoration of urethral function in SD rats

• Nl, nontreated control, bilateral sciatic nerve transection w/ periurethral injection of saline, MDCs, fibroblasts, or MDC/fibroblast mixture

Stem Cells and Incontinence

• Histologic exam showed muscular atrophy in saline group, and new striated muscle fibers at sites of MDC injection in the MDC group but not fibroblast group

• LPP increased in both MDCs and fibroblast injection, but only MDCs improved the urethral muscle strip contractility

• Urinary retention developed in the high dose fibroblast group only

Stem Cells in Human Clinical Trials

• Strasser et al. Autologous myoblasts & fibroblasts vs collagen for treatment of SUI in women: a RCT

• 63 women with SUI

• Randomized to transurethral US guided injection of autologous myoblasts and fibroblasts (42) or transurethral collagen (21)

• 1° outcomes: incontinence score 0-6 on VD, 24 hr pad test, questionnaire, contractility & thickness of rhabdosphincter

Stem Cells in Human Clinical Trials

• ITT analysis

• 12m follow upMeasure Autolgous cells Collagen

Overall cure 38/42 2/21

Incont score 6 →0 0 →0

Thickness 2.13mm p=< 0.0001

3.38 2.32

Contractility 0.58mm p=<0.0001

1.56 0.67

Adult Stem Cell Therapy for SUIMitterberger et al BJU Int 2007

• 123 women with SUI

• Follow up of 12 mos

• Skeletal muscle biopsy from upper arm

• Fibroblasts & myoblasts obtained and cultured x 7 weeks

• Using ultrasound guidance myoblasts injected into rhabdosphincter

• submucosal injection offibroblast +collagen carrier

• Pre and post injection eval with I-QOL, UDS, morphology & fxn of urethra and rhabdosphincter

Adult Stem Cell Therapy for SUIMitterberger et al Eur Urol 2007

• One year results– 94/119 (79%) cured

– 16/119 (13%) significantly improved

– 9/119 (8%) slightly improved

– 4 lost to follow up

Stem Cell Therapy for SUI

• Stem cell therapy of SUI may the possibility to morphologically and functionally reconstruct the urethra and the rhabdosphincter

• Questions– Cost– Durability– Patient selection– Controlled trials

Radiofrequency Thermal Energy for SUI

• Transvaginal delivery causes replacement of endopelvic fascia with fibrotic tissue -shortens, stiffens and thickens fascia increasing urethral & bladder neck support (75-90ºC)

• Transurethral delivery (65-75ºC) “causes tissue micro remodelingwith creation of small regions of altered tissue compliance withoutgross alteration in tissue morphology”

Transvaginal – SURx System

Transurethral – Renessa Device

4 RFeelectrodes

Room tempsterile H2O

Transvaginal Radiofrequency

• Multicenter study of 120 women at 10 sites– Non-randomized, non-controlled– Urethral hypermobility and ALPP > 90 cmH2O– Avg. operative time 30 min– Avg. Temp 82º C

• Successful outcome “cured or improved”at 12 months (109 patients) 73%– 26% reported no IE’s– 66 (61%) objective cure on UDS– 39% extremely satisfied, 16% moderately satisfied– No complications reported

Dmochowski, et al: J Urol 2003;169:1028-1032

Transurethral RadiofrequencyLenihan: Am J Obstet Gynecol 2005;192:1995-2001

• 173 patients at 10 US sites (Novasys Medical)• Urodynamic SUI, hypermobility, ALPP >60 cmH2O• No prior surgical or bulking agent treatment• Randomized to RF (110) or Sham (63)• Primary efficacy variable change in I-QOL of at least

10 points• Only reported on those women with moderate to

severe SUI based on I-QOL 0-60– 43 RF and 30 Sham

• 74% of treated and 50% of sham had > 10 point improvement in I-QOL (p=.03)

Transurethral RadiofrequencyAppell RA, et al Neurourol Urodynam 2006;25:331-336

• 173 patients, evaluable population for QoL was 142, 89 treatment (80.1%) and 53 sham (84.1%)

• Results at 12 months (> 10 point improvement in QOL):

Treatment Sham

All patients 48% 44% p=0.7

Mod to severe SUI 74% 50% p=.03

Mild SUI 20% 35% p=0.2

Change in ALPP 13.2cmH2O -2.0cmH2O p=.02

• Dysuria only AE different among 2 groups 9.1%vs 1.6%

Transurethral Radiofrequency3 Year Data

• 26 women available at 3 years– 5 underwent additional treatments for SUI

– 21 included in analysis

– 18 had IEF data

• 50% achieved a 50% or greater reduction in IEF– 3 patients no leaks on diary

– 3 patients worse

– Median change -1 IEF/day

Appell, et al Future Drugs 2007;4:1-7

Radiofrequency for SUISummary

• Minimal available data on transurethral and transvaginal techniques

• Transurethral seems less invasive with less requirement for anesthesia– “office procedure”

• Primary efficacy outcome parameters are non-traditional– How well does it really work?

• No definitive advantage over bulking agents

Mid Urethral Slings: Indications, Techniques and Objective Data

Victor W. Nitti

Introduction of the Mid Urethral Synthetic Sling In The Late 1990’s

• TVT introduced in 1996• Changed the way female stress incontinence is

treated• Applicable to the majority of cases of female

SUI• Retropubic mid urethral synthetic sling is the

new “gold standard”• Transobturator mid urethral sling introduced

later

Why have they become so popular?

• Proper mechanism of action to treat most SUI• Easy for patient

– Choice of anesthesia

• Easy for surgeon• Short operative time• Low morbidity• Rapid recovery• Efficacy compares favorably to any other procedure• Introduction of transobturator approach

How important is the brand of sling?

• Vast majority of data on TVT• A few comparative studies have shown equal efficacy

in the short term (e.g. TVT vs. SPARC)• For retropubic approach transvaginal appears equivalent

to suprapubic• Most important is the type of mesh

– Polypropylene, macropore, woven

• Each brand offers different features which may appeal to different surgeons– No distinct efficacy advantages as long as proper material

• “Homemade” slings show similar efficacy

Optimal Synthetic?

• Monofilament

• Inert

• Large pore size– Resist Infection

– Bacteria proliferate in micropores

– Macrophages unable to clear bacteria if pore size <10 microns*

– Tissue and blood vessel ingrowth at pore size > 75 microns*

* Based on data from hernia repair

Loosely woven polypropylene

Lateral Edge & Pore Pictures

Advantage Mesh

ObTape

UreTexSparc/Monarc

TVT

Examples of Midurethral Slings

TVT SPARC

LYNX

Midurethral SlingsMechanism of Action

• Dynamic kinking of the urethra with stress

• Both work without curing hypermobility– TVT

• Atherton and Stanton, 2000

• Sarlos, et al, 2003

• Lo, et al 2004

– TOT• Minaglia, et al, 2005

• Why do they sometimes work when there is no hypermobility?

TVT Results

• Large number of prospectivestudies in the literature by multiple authors from different countries show that at 1,2,3,4 and 5 years:– Cure 84-88%

– Significant improvement 7-10%

– Failure ~ 5-8%

Randomized Trial of TVT vs. Colposuspension:5 Year Follow up

Ward and Hilton BJOG 2008;115:226-33

Of 344 women 177 returned for f/u at 5 years and 119 had full subjective and objective data set (72 TVT, 49CS)

Parameter TVT CSNeg. 1 hour pad test* 81% 90% p=0.21De novo urgency 2% 5%De novo UUI 1% 4%No leakage any circumstances 39% 46%Cure stress leakage 63% 70%Satisfied or very satisfied 91% 90%Surgery for prolapse 1.8% 7.5% p=.025Tape/suture complications 6pts. 0 pts.

TVT as effective in curing SUI as colposuspension at 5 years.Effect of both procedures on cure of SI and increased QOL maintained in long term* Primary outcome measure

TVT 7 Year Data

• 90 consecutive women with SUI had TVT 1995-1996

• 80 available for followup

• Mean followup 91 months (78-100)

• Subjective cure in 80 women = 81.3%– 16.3% improved

• Objective cure in 64 women = 84.4%

Nilsson, et al: Obstet Gynecol 2004;104:1259

Retropubic MidurethralSynthetic Slings

• Literature supports use in– Obese patients

– Elderly

– Failed prior surgery

– Low ALPP or MUCP with hypermobility

– Concurrent prolapse repair

Retropubic MidurethralSynthetic Slings Outcomes

• Reports for low ALPP and MUCP are mixed– Some show identical results

• Decreased success with lower MUCP (<20)• 74% vs. 85% cure - Rezapoor 2001

– Overall success is probably slightly lower

– No mention of mobility

Outcomes of TVT in ISD and Non-ISD

• Retrospective study of 111 patients– 31 with ISD– 80 with non-ISD

• ISD defined as:– ALPP < 60 cmH2O or MUCP < 20 cmH2O– No mention of urethral mobility

• No difference in cure rates at 12 months– 74% for ISD– 84% for non-ISD

Bai et al Int J Urogyn 2007

Urethral Mobility Not MUCP Predictive of TVT Outcome

• Urethral mobility determined on lateral cystogram• Mean f/u 9 months• Objective success based on urethral mobility (p=0.023)

– > 60° - 97%– 30-60° - 86%– < 30° - 70%

• Strong association of urethral mobility and previous surgical failure

• No difference in success based on MUCP (p=0.65)– < 20 cmH2O - 80%– > 20 cmH2O - 85%

Fritel, et al: J Urol 2002; 168:2472-2475

Complications

• Minor complications – Transient voiding

dysfunction

– Hematoma formation

– Bladder perforation (5%)

– Vaginal extrusion of tape

• Major Complications – Tape erosion into urethra

or bladder

– Vascular injury &/or Neuropathy

– Bowel injury

– Urinary retention (2-3%)

Significant Complications

• Operative Injuries– Major vascular, nerve, bowel, ureter

• Incidence of any = 0.08% 1

– Bleeding requiring intervention• 0.16 - 0.8% 1,2

• Late– Urinary tract erosion

• Can eliminate major vascular and bowel injury and minimize erosion into the bladder if retropubic space is avoided

1. Agostini, et al: Eur J Obstet Gynecol Reprod Biology 2006;124:237-2392. Kolle, et al: Am J Obstet Gynecol 2005;193:2045-2049

Trans Obturator Slings

• Avoid retropubic space

• Theoretical decrease in potential complications– Bladder perforation reported

• Like the retropubic seems to work by dynamic urethral kinking

• Theoretical decrease in voiding dysfunction

Trans Obturator Slings

• Outside – In– Mentor, AMS, Bard

– Boston Scientific, etc

• Inside - Out– TVT - Obturator

Retropubic and Transobturator MUSMechanism of Action

• Dynamic kinking of the urethra with stress• Both work without curing hypermobility

– TVT• Atherton and Stanton: BJOC 2000;107:1354-1359• Sarlos et al: Int Urogynecol J 2003;14:385-388• Lo et al: Urology 2004;63:671-675

– TOT• Minaglia et al: Urology 2005;65:55-59

• Why do they sometimes work when there is no hypermobility?

Transobturator Slings

• Data on transobturator slings maturing• Most data on the TOT (Mentor/Porges)

– The Obtape and Uratape have had the highest complications and the material has actually changed

• Composition of the tape is most important• No distinct advantage of brand or approach

(outside-in vs. inside-out)– Surgeon preference

Obturator canal

Urethra

Safe entry zone for needle insertion

Adductor longus

insertion

Obturator Anatomy

AnatomyWhiteside and Walters Int Urogynecol J 2004; 15:223-226

• Using Monarc technique tape goes through:– Gracilis– Adductor brevis– Obturator externus– Obturator membrane– Obturator internus (through or beneath)– Periurethral endopelvic connective tissue)

• Tape sits below levator ani

• Vasculature in the region variable

AnatomyWhiteside and Walters Int Urogynecol J 2004; 15:223-226

Distances from transobturator sling to selected structures (bilaterally in 6 cadavers)

Structure Median distance (cm) Range (cm)

Obturator canal 2.3 +0.4 1.5 – 2.8

Ant. obturator nerve 2.6 +0.8 1.5 – 4.5

Post obturator nerve 2.5 +0.7 1.2 – 3.5

Most medial vessel* 1.1 +0.5 0.2 – 1.8

* Most < 5 mm, one was > 5 mm

Transobturator Tape Outside-InPeer Reviewed Literature

• Delorme E at al Prog Urol 2003;13:656– Uratape / Obtape– 32 patients, mean f/u = 17 months (13-29)– 90.6% cures, 9.4% improved– No intraop complications– 1 prolonged retention (4 weeks)– 5 with obstructive voiding 2 de novo UUI– No difference in results base on MUCP

Transobturator Tape Outside-InPeer Reviewed Literature

• Deval at al: Eur Urol 2006;49:373-377– 2 centers in French

– Obtape

– SUI with urethral hypermobility

– 129 patients, mean f/u = 17 months (8-28)

– Subjective cure = 77.5%, improvement 18%

– Objective cure = 89.9%

– 6.2% vaginal extrusion, 1.5% obturator abscess

– 1.5% needed loosening

Transobturator Tape Inside-OutPeer Reviewed Literature

• Leval Eur Urol 2003;44:724– 107 patients – feasibility study – outcomes not reported– Mean operative time 14 minutes (7-20)– No bladder or urethral injuries

• Bonnet, et al J Urol 2005;173:1223-8– 12 cadaveric dissections - safe, consistent, reproducible path

• Reisenauer, et al: Eur Obstet Gynecol Reprod Biol e pub. 12/26/05– 5 corpse dissection after standard surgical procedure– Distance between tape and major neurovascular structures shows

slight individual variation but no major risk of injury

Meta analysis of Literature on Retropubic vs. Transobturator Approach MUS

• 6 randomized trials and 11 cohort studies chosen from 303 extracted articles– 492 women randomized to RP or TO– 2099 women in cohort studies received RP or TO

• No difference in subjective failure• TO had decreased risk of complications• Still unclear which approach is superior

– Would require an RTC of 30,000 women to demonstrate equivalence

Sung, et al Am J Ob Gyn 2007;

Risk of subjective failureRCT’s 5.7% TO vs. 7.8% RPCohort studies 15.4% TO vs. 12.8% RP

Sung, et al Am J Ob Gyn 2007;

Risk of complicationRCT’s 0.8% TO vs. 12.2% RP*Cohort studies 0.8% TO vs. 5.5% RP*

Sung, et al Am J Ob Gyn 2007; * Includes bladder perforation2 patients in RP group returned to OR for bleeding

De novo Irritative SymptomsRCT’s 11.4% TO vs. 18.8% RPCohort studies 4.1% TO vs. 9.2% RP

Sung, et al Am J Ob Gyn 2007;

TVT vs. TVT-O

• Multicenter study in Finland of 267 women– 136 TVT, 131 TVT-O

• Symptomatic SUI, no UDS• At 2 months objective cure was the same (98.5% vs.

95.4%)• Complications were not less in the TVT-O group

– 1 transfusion in the TVT group– Groin pain considered a complication

• TVT-O group required more post op opiates– 21.4 %vs. 11.8%

Laurikainen, et al Obstet Gynecol 2007; 109:4-11

Comparison of Transobturator Techniques

• Prospective, non-randomized observational study

• 50 TVT-O and 50 Monarch

• Cure rates at one year similar (94% vs. 90%)

• Complications similar

• Less dissection for inside-out technique

Debodinance, et al EJOG 2006

Outcomes in Low Urethral Resistance

• TVT-O1

– 43 women with USUI had TVT-O, no mention of mobility– Cure rates if ALPP > 60 cm H2O = 71% (24/31)– Cure rate if ALPP <60 H2O = 25% (3/12)– Odds ratio for persistent SUI 12x higher if ALPP <60 H2O

• MONARCH vs TVT2

– Retrospective study– USUI with hypermobility– No preference for procedure except if MUCP < 20 cmH20, TVT– ROC analysis found MUCP <42 cmH2O as cut point

• Objective and subjective failure at 3 months 3% and 13% for TVT vs. 16% and 23% for MONARCH (RR=5.89/1.74)

1. O’Connor, et al Neurourol Urodyn 2006;25:685-882. Miller, et al Obstet Gynecol 2006;195:1799-1804

Transobturator Slings

• No consistent selection criteria have been reported though most experts think it is comparable to retropubic– Obesity– Elderly– Prior surgery– Fixed urethra– Low ALPP– With prolapse repair

pubourethral

ligament

pubispubis bladderbladder

Pre Pubic Mid Urethral Sling

Pre Pubic TVT

• 164 women with SUI• Mean follow-up 20 months (14-30)• Objective cure rate in 82.3%

– 4.3% improved– 13.4% failed– Patient view of success and satisfaction was 85.4% and

86%.

• No significant intraoperative complications• All patients voided on the first day

– The mean post void residual urine was 45 ml

Daher et al Gynecol Obstet Fertil 2005;33 570-76

Prefyx PPS™ SystemBoston Scientific

Prefyx PPS™ System Prefyx PPS™ System

• Data from Boston Scientific, not peer reviewed

• 100 patients results at 3 months on 69

• 72% at 3 months and 73% at 12 months has a 0 gm acute pad test

• One sling removed due to “foreign body reaction”

Single-Incision Mini Slings

• TVT- S, AMS Miniarc• Designed to be placed

via a single vaginal incision

• No exit points• Minimal data available• ?? Easier insertion

– Not yet shown

• ?? Quicker recovery• ?? Office procedure

TVT – Secure

• Can be placed as a “U” or a Hammock

• Mimics Retropubic or TO• Single Incision

AMS MiniArc

• Placed as a Hammock• Mimics TO• Single Incision

Single Incision Slings Published Dataas of 3/4/2008

• TVT-Secure– 1 Manuscript:

– Matan and Masata Ceska Gynekol 2007;72:42-9

– 15 women with 1-3 months follow up

– 93% cure

• AMS MiniArc– none

MiniArc White Paper from AMS

• Retrospective, multicenter, non-randomized study of 60 patients at 5 sites– 56 (93.3%) completed 6 week f/u– 52 (86.7%) completed 12 week f/u

• At 12 weeks 92.3% confirmed dry by either objective or subjective data

• IIQ-7 and UDI-6 scores decreased significantly at 6 and 12 wks

• Minimal complications / pain

• Is this an acceptable level of evidence for routine use?

Moore RD, Erickson T, Feagins B, Miklos JR, Serels S, Van Drie D 9/07

Why Adapt Brand New TechnologyOutside of a Clinical Trial?

• Data supports it use

• Shown to be safe

• In the absence of data:– Fills an unmet need

– Fills a need in a particular patient

– Patient/physician decision with full disclosure of what is known and not known in a situation that may offer a benefit over a more accepted procedure

• PATIENTS MUST BE FULLY INFORMED

Pubovaginal Sling for “Complex SUI”

Harriette M. Scarpero

Are Midurethral Slings the Only Operation We Should Do?

• There is still a role for standard PV sling and more limited for Burch procedure

• For PV sling:– Complex reconstructive cases

– Prior problem with synthetic

– Current problem with synthetic

– Fixed urethra

– Patient / surgeon preference for autologous tissue

Pubovaginal Slings

• Not all pubovaginal slings are the same

• Differ by material, size of sling, and bone anchor suspension

• Analysis of success of slings is hampered by this

• Definition: autologous or other biologic sling placed at the bladder neck

Autologous Pubovaginal Sling

• Autologous rectus fascia or fascia lata are the gold standard materials

• Cost effective, available, and biocompatible by definition

• In studies with >12m follow-up, cure rates vary 50-100%, average cure of 84%

• One new RCT of AFS vs Burch

Patient Satisfaction with Autologous Slings

• Latini et al, J Urol 2004, 85% dry/improved, 83% report + effect on life at 4.4 yrs

• Similar rates of improvement in QOL and satisfaction in 2 other recent studies (Richter et al & Morgan et al)

Disadvantages of PV Sling

• Greater morbidity and convalescence

• Cannot be done with local anesthesia alone

• Not outpatient procedure

• Delayed return to normal voiding

Complications of Autologous Tissues

• Harvest site infection, seroma, hematoma, herniation, or site pain

• Transient obstructive symptoms/ delayed return to normal voiding

• Urinary retention

• Rare erosion

Allograft slings

• Lyophilized dura mater, pericardium, fascia lata, acellular dermis

• Appeal is avoids time and morbidity of fascial harvest, yet maintain biocompatibility and lower risk of erosion

• Success with cadaveric allografts in studies with > 12 m follow-up, is 40-100%, mean rate of 79%

Efficacy of Allografts

• Studies calling into question the efficacy of cadaveric tissues present for many years

• Fitzgerald et al, BJU Int 1999

• Soergel et al, Int Urogynecol J 2001

• Chaikin & Blaivas, J Urol 1998

• O’Reilly & , J Urol,2002

Cadaveric Acellular Dermal Allograft Outcomes

• Crivellaro et al, prospective series of 253 patients: 57% dry in Type II and 55% dry in Type III at 18 m

• Wang et al, 95% cured/improved in 111 pts at 36 m

• Owens & Winters, only 32% were dry at 14.8 m and 24% occurred within 6-14 m

Allograft Sling

• Mechanisms of allograft failure need further elucidation

• Benefits of allograft may only be relevant in a select group of patients unwilling or unable to undergo a fascial harvest (CAPS data?)

Other Concerns with Allografts

• Tissue rejection- not reported to date

• Disease transmission (HIV, CJD, bacterial)– DNA found in freeze dried CFL, solvent

dehydrated CFL and acellular dermis

– In 85% of institutions, those providing the allografts had little or no knowledge of tissue banking and allograft transplantation biology. Surgeon involved in selection in only 15% (Lavernia CJ, J of Arthroplasty, 2004)

Xenografts

• DermMatrix™, Pelvicol™, InteXen™ (porcine dermis)

• Porcine dermis is the only xenograft with long-term follow-up and randomized comparison to other sling alternatives. Studies involve Pelvicol as Bladder neck and midurethral sling.

Porcine Dermis Outcomes at the Bladder Neck

• Giri et al, J of Urol 2006

• 101 nonrandomized patients with SUI underwent RF or PD sling procedure

• Primary Outcome measure patient perceived success at 36m = 80.4% RF vs. 54% in PD

• Recurrent SUI rate by UDS= 37.5% in PD vs. 6.5% RF

Other Porcine Acellular Products

• Porcine small intestinal submucosa (SIS) marketed for PV sling use as STRATASIS®

• Bovine pericardium: UroPatch™, Veritas™

• Little data on efficacy of these materials for SUI surgery

Xenograft Slings

• Xenografts– Porcine dermis – Pelvicol, Dermatrix, InteXen

– Bovine pericardium

– Porcine small intestine submucosa – SIS

• Best peer-reviewed data on porcine dermis

Pelvicol vs. TVT 3 Year FollowupAbdel-Fattah et al: Eur Urol 2004;46:629-635

• 142 women with SUI randomized to TVT (68) or Pelvicol (74) midurethral sling– 3 year questionnaire followup

– 90% returned questionnaire (3 died, 11 LTFU)

• Complete cure in 79% vs. 77% (assuming non-responders were failures)

• Additional significant improvement in 4.5% vs. 9.7%

• No differences in complications

• Essentially no differences in outcomes

Pubovaginal SlingSummary

• Excellent long term outcomes with autologous fascia – but tradeoff is increased convalescence and morbidity

• Biological sling materials and techniques offer decreased OR time and convalescence

• Patients should be explained advantages and disadvantages of each, what is known and what is unknown

• Long-term and chronic complications are similar for all operations– Voiding dysfunction, retention, de novo irritative Sx’s

Comparison of Efficacy of Burch, PV Sling, and TVT for SUI

Bai SW et al. Gynecol & Obstet, 2005

• 92 women randomly assigned to the 3 procedures: – Burch 33, PVS 28, and TVT 31

• Pt characteristics, UDS, cure rates at 3,6, 12mos and complication rates compared:– No statistically significant difference in patient

characteristics or preop UDS results

– No difference in 3 or 6 month cure rates

– 1 year cure was statistically higher in the pubovaginal sling group

Comparison of Efficacy of Burch, PV Sling, and TVT for SUI

Bai SW et al. Gynecol & Obstet, 2005

Procedure 1 yr % Cure Retention or

Obstructive sx

DO

Burch

N=33

87.8 0

1 hesitancy

3

PV sling

N=28

92.8 2 0

TVT

N=31

87 4 0

Burch Colposuspension vs Fascial Sling to Reduce Urinary SUI

• Albo ME, Richter HE, Brubaker L et al. N Engl J Med 2007

• Known as the SISTEr Trial (Stress Incontinence Surgical Treatment Efficacy Trial)

• Clinical question:– Is there any difference in the efficacy and/or safety

of an AFS compared to a Burch for

SUI?

Methods

• Design: RCT• Blinding: Unblinded at/post surgery• Follow-up period: 24 months• Patients: 655 patients randomized

– Burch 329/328– AF sling 326

• Setting: Multi center• Patient followup: 255/ 265 completed FU• Outcomes: (Primary) neg pad test, no UI on 3d diary,

– (SUI specific) neg cough/Valsalva stress test, no self reported symptoms, no retreatment

– (Secondary) postop UUI, voiding dysfunction, and adverse events

Results

• Success rates higher for sling group for both overall and SUI specific success (47% vs 38%, p=0.01 & 66% vs 49%, p<0.001)

• Higher rates of UTI, difficulty voiding and postop UUI in the sling group

• No difference in serious adverse events (13% vs 10%, p=0.20)

• Only the sling group required surgical procedures for obstructive voiding sx/retention postop (N=19)

• Sling group had higher rates of satisfaction

Results Incision• Single suprapubic incision

about 2 cm cephalad to the anterior border of the symphysis– Upper border of pubic hair

line

– Minimize size of incision when desirable (5-6 cm)

• If patient has an old incision, usually use it

Closure and Tying of Sling• Close the vaginal wall

prior to tying the sling

• Tie each end of the sling together across the midline with absolutely no tension– 2 - 3 fingers should fit

between rectus fascia and top of air knot

Role of PVS 2008

• Fixed urethra (better efficacy over TVT)– Patient choice (70% short term success with TVT)– Prefer autologous – best long term data– Older patients consider biological (porcine dermis)

• Prior problematic synthetic sling• Significant radiation changes• Simultaneous urethral reconstruction / urethral

diverticulectomy• Patient preference for autologous tissue

Management of Complicationsof SUI Surgery

Harriette M. Scarpero

Complications

• Obstruction

• De novo urgency/urge incontinence

• Extrusion

• Erosion– Bladder

– Urethra

Iatrogenic Obstruction After Incontinence Surgery - Treatment

• Conservative– CIC– Pharmacotherapy– Biofeedback– Dilation (??)

• Definitive– Urethrolysis

• Transvaginal• Retropubic• Suprameatal (infrapubic)

– Sling incision– For midurethral synthetic

slings can “loosen” in first 5-7 days

Iatrogenic Obstruction After Incontinence Surgery - Treatment

• Conservative– CIC– Pharmacotherapy– Biofeedback– Dilation (??)

• Definitive– Urethrolysis

• Transvaginal• Retropubic• Suprameatal (infrapubic)

– Sling incision– For midurethral synthetic

slings can “loosen” in first 5-7 days

Sling Incision

• Inverted U or midline incision

• Isolation of sling in the midline

• Incision of the sling

• For biological sling, if cannot be identified, proceed with formal transvaginalurethrolysis

Sling Incision

• Freeing of the sling from the underlying urethra– May require sharp or

blunt dissection

• No perforation of the endopelvic fascia

• No freeing of the urethra from the pubic bone

• Closure of the vaginal wall

Sling Incision Results

N Type SuccessSUI

Nitti, et al 19 Midline Incision 84% 17%

Amundsen, et al 32 Various 94% retention9%

67% UUI

Goldman 14 Midline Incision 93%21%

Obstruction FromSynthetic Midurethral Sling

• Intervention required in about 2% of cases• Critical to identify and cut or loosen sling• Urethrolysis without identifying TVT likely to

fail• In cases of early intervention (up to 14 days)

may be able to loosen by pulling down• After 10-14 days need to incise as TVT is

ingrown with native tissue • Chronicallly can become a tight band

Technique of Mid Urethral Sling Loosening at 1-2 weeks

• Infiltrate anterior vaginal wall with 1% lidocaine

• Open vaginal suture line• The sling is identified and hooked with a right-

angle clamp• Spreading of the right angle clamp or

downward traction on the tape will usually loosen it (1-2 cm)

• If the tape is fixed, it can be cut• Reapproximate vaginal wall

TVT Intervention Results

N Type Success

Klutke, et al* 17 Midline Incision 100% normal emptying

Rardin, et al** 23 Midline Incision 100% normal emptyingLoosening 30% complete resol.

irritative sx70% partial resol.

irritative sx

* Recurrent SUI in 6%** Significant recurrent SUI 13%

26% recurrent SUI, but significantly better than prior to TVT

Obstructing TVT at 11 months Obstructing TVT – Retention at 3 Months

Transvaginal Urethrolysis

• Inverted U incision

• Lateral dissection above periurethral fascia

• Endopelvic fascia sharply perforated and retropubic space entered

Transvaginal Urethrolysis

• Sharp and blunt dissection freeing the urethra from the undersurface of the pubic bone

• Index finger placed between pubic bone and urethra

• Place penrose drain around the urethra

Retropubic Urethrolysis

• Mobilization of urethra by sharp dissection– Restore complete mobility to anterior vaginal wall

• Paravaginal repair

• Interposition of omentum between urethra and pubic bone

Urethrolysis ResultsN Type Success SUI

Foster & McGuire 48 Transvaginal 65% 0

Nitti & Raz 42 Transvaginal 71% 0

Cross, et al 39 Transvaginal 72% 3%

Goldman, et al 32 Transvaginal 84% 19%

Petrou, et al 32 Suprameatal 67% 3%

Webster & Kreder 15 Retropubic 93% 13%

Petrou & Young 12 Retropubic 83% 18%

Carr & Webster 54 Mixed 78% 14%

Vaginal Extrusion

• ? Observation

• ? Topical estrogen

• Bury

• Excise eroded portion

• Excise entire sling

Ward & Hilton 5yr extension identified 2 late “erosions,” one vaginal and one bladder

Vaginal ExtrusionWhat’s the Difference?

Bladder and Urethral Erosions

• ? Observation

• Endoscopic excision

• Open Excision

Erosion or Misplaced Sling?Vesicovaginal Fistula after Midurethral

Sling

• Urinary incontinence worse within 3 days postop- constant

• Not visible by cystoscopy

• Tape found through detrusor near bladder neck

• Issue of technique

Vesicovaginal Fistula Related to MUPS

Closing Thoughts On Surgery For SUI In 2008

Is Efficacy the Only Factor That Determines Procedure?

• There are times when one may choose a potentially less efficacious procedure in order to lessen potential morbidity or recovery time– e.g. a retropubic MUSS instead of an autologous

PVS in case of a non-mobile urethra

– e.g. biological material instead of autologous fascia for a PVS in an elderly or obese woman

Patient’sCondition

What ProcedureTo Do?

OutcomesData

SurgeonPreference

MorbidityRecovery

Risk

Clinical Effectiveness in Surgery

• With pharmacotherapy:clinical effectiveness = efficacy + tolerability

• Can the same principle be applied to surgical therapy?

• “Clinical effectiveness in surgery” = efficacy + safety + recovery + risk

Nitti VW: Curr Urol Rep 2005;6:319-321

OFFICE OF EDUCATION Improving Practice and Patient Care Through Affordable Quality Urological Education

AUA EDUCATIONAL PRODUCTS

2008 AUA Courses

Subject-Oriented Seminars

∗ AUA Annual Review Course June 5-8—Dallas, TX Course Directors: Daniel A. Shoskes, MD & Allen F. Morey, MD

∗ Basic Sciences for Urology Residents June 13-18—Charlottesville, VA Course Director: William Steers, MD

∗ 2008 Summer Research Conference August 7-9— Baltimore, MD Course Director: Arthur L. Burnett, MD

∗ Cutting Edge Topics in Urology October 3-5—Scottsdale, AZ Course Director: Gopal Badlani, MD

∗ Female Urology & Advanced Urodynamics October 16-18—New Orleans, LA Course Director: Victor Nitti, MD

∗ 4th International Congress on the History of Urology November 7-9—Baltimore, MD Rainer Engel, MD

∗ Female Sexual Dysfunction December 12-13—Washington, DC Course Director: Irwin Goldstein, MD

Surgical Learning Center Courses

∗ Hand-assisted Laparoscopy: Nephrectomy, Nephroutererectomy & Partial Nephrectomy

June 7-8—Houston, TX Course Director: R. Ernest Sosa, MD

∗ Introductory Urodynamics August 1-3—Reno, NV Course Director: Timothy Boone, MD

∗ Hands-on Ultrasound October 25-26—Dallas, TX Course Director: Pat F. Fulgham, MD

∗ Mentored Laparoscopy November 8-9—Houston, TX Course Director: Stephen Y. Nakada, MD

∗ Hand-assisted Laparoscopy: Nephrectomy, Nephroutererectomy & Partial Nephrectomy

December 6-7—Houston, TX Course Director: R. Ernest Sosa, MD

∗ AUA Coding Seminars – Move to the Forefront July 12— Las Vegas, NV August 9— Washington, DC September 20—Tampa, FL

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