1. A Practical Approach To Urogynecology

2. Who Cares? Is this Really important?
Incontinence affects 33 million Americans (17% of the population)
Direct costs to USA in 2000: $19.5 Billion dollars
Significant Adverse effects in multiple quality of life domains

3. Barriers to Treatment
Women develop coping mechanisms like the avoidance of activities that provoke the leakage, wearing dark clothes, avoiding intercouse, and social interactions with others.

4. Barriers to Treatment Normal part of aging Nothing can be done
Surgical treatment is invasive
Catheters and daily management products are the best solutions

5. Incontinence Myths
DON’T CALL A PLUMBER!!!!!
They’re too expensive!

6. Barriers to Treatment
Feeling of not being equipped to offer effective solutions
“ I do not have the time”
Feeling that incontinence is a “lost leader”
Belief that urinary incontinece just isn’t a serious concern

7. What is Incontinence?
Loss of voluntary control over your urinary functions
May consist of the loss of a few drops of urine while coughing or laughing, or urine loss with a sudden urge to urinate

8. Classification of Incontinence
Stress – loss of urine when the abdomen is under physical stress (e.g. coughing, laughing, sneezing, running)
Urge – a sudden, strong urge to urinate combined with a sudden, uncontrollable leakage of urine (OVER ACTIVE BLADDER)

9. Classification of Incontinence
Mixed (stress and urge)
Overflow – frequent or constant dribble of urine

10. Transient Incontinence: DIAPPERS
D Delirium or Acute Confusion
I Infection
A Atrophic Vaginitis
P Phamacologic Agents
P Psychotic Disorders
E Excessive Urine output (CHF)
R Restricted Mobility
S Stool Impaction
Consider with Frail and Elderly Women

11. Secondary Causes Interstitial Cystitis Multiple Sclerosis
Parkinson’s Disease
Diabetes Mellitus and Insipidus
Bladder Cancer
Urethral Diverticulum
Fistula

12. Lifestyle Factors
Caffeine
Alcohol
Opiods
Sedentary
Cigarette Smoking

13. Predisposing Factors Vaginal Delivery Age Genetics Obesity
Prior Surgery
Chronic Lung Disease/Smoking
Medications

14. Evaluation of Pelvic Floor Disorders
History
Physical Examination
Bedside Simple Cystometry
Determination of Post Void Residual
Supine and Standing Stress Test
Urinalysis

15. Indications for Complex Urodynamic Evaluation
Planning Surgery
Mixed or confusing picture
History inconsistent with Exam
Elevated Post Void Residuals
Failed Conservative Treatment
History of Prior Pelvic floor Surgery
History of Pelvic Radiation

16. Other Tests Voiding Diary Urine Cytology Cystoscopy
Electrophysiologic Testing
Radiologic Imaging of Pelvic Floor

17. Signs of Complicated Incontinence
Recurrent Incontinence
Continuous Leakage
Treatment Failure
Prolapse Beyond Hymen
Elevated Post Void Residual
Pain, Hematuria, Recurrent UTI
History of Prior Pelvic floor Surgery
History of Pelvic Radiation

18. How Does Stress Incontinence Occur?

19. How Does Stress Incontinence Occur?
Weak Connective Tissue Supports
Weak Musculature of pelvic floor
Weakening of the bladder neck spinchter
Abnormal nervous system

23. T

26. Treatments for Stress Incontinence
Alpha Agonists *
Tricyclic Antidepressants*
Urethral Bulking Agents
Active use of Kegel with Provocative Event
Catheters/Absorbent Products/Mechanical Devices
EXMI Chair
Surgery
*non FDA Approved Indication

27. Surgery Highly effective minimally invasive sling surgery
Burch Retropubic Colposuspension
Needle Suspension Procedures
Kelly Plication
Traditional Pubovaginal Sling
Highly effective minimally invasive sling surgery
now available

28. Traditional Approach to Surgical Management
Of Urinary Stress Incontinence
No Hypermobility
Normal Pressure Urethra
Burch
Hypermobility
Sling
ISD
Periurethral Bulking Agents
No Hypermobility

29. Principles of Action

30. TVT
Kohli N, Miklos J, Lucente V. Tension-free vaginal tape: A minimally invasive technique for treating female SUI. Contemporary OB/GYN; Gynecare reprint: 1 – 10.

31. Trans-Obturator Approach
Easy to implant
Operative time is reduced
Minimally invasive
Local, regional or general anesthesia can be utilized

33. The Micturition Cycle Storage phase Emptying phase Bladder pressure
Normal desire to void
Bladder filling
The normal micturition cycle consists of a storage phase and an emptying phase.
The storage phase encompasses bladder filling, the first sensation to void, and the desire to void.
The emptying phase is characterized by a volitional contraction of the detrusor muscle leading to a rise in bladder pressure and emptying of the bladder. As the bladder begins to refill, the cycle is repeated.
First sensation to void
Bladder filling

35. Innervation of the LUT Sympathetic Parasympathetic T10-L2 Somatic
Inferior mesenteric ganglion
Sympathetic
Trigone
Urethra
Hypogastric nerves
Parasympathetic
Pelvic nerves
T10-L2
Bladder emptying is a complex process involving communication among several parts of the central nervous system, or CNS. These include the cerebral cortex, limbic system, hypothalamus, thalamus, basal ganglia, cerebellum, brain stem, and spinal cord, linked to each other and to the peripheral nervous system.
The nerves responsible for micturition pass through the S2 through S4 segments of the spinal cord.
External urethral sphincter
Somatic
S2-S4
Pudendal nerves
Muscles of the pelvic floor
Adapted from Abrams P, Wein AJ. The Overactive Bladder: A Widespread and Treatable Condition. Erik Sparre Medical AB; 1998.

36. Distribution of Cholinergic and Adrenergic Receptors in the LUT
Μ = Muscarinic
Ν = Nicotinic
α = α1-adrenergic
β = β2-adrenergic
Detrusor muscle (M,β)
Trigone (α)
The distributions of cholinergic and adrenergic receptors have been characterized in the lower urinary tract.
The muscarinic M3 receptor is located in the detrusor smooth muscle and is the primary mediator of bladder contraction.
The M2 receptor is also believed to mediate detrusor contraction, by inhibiting sympathetically mediated detrusor relaxation in rats.
The 2-adrenergic receptors are also located in detrusor muscle and appear to be involved in bladder relaxation.
The 1-adrenergic receptors predominate in the trigone, bladder neck, and urethra, and may be involved in contraction.
Nicotinic receptors are located in the pelvic floor and play a role in contraction.
Pelvic floor (N)
Bladder neck (α)
Urethra (α)
Adapted from Abrams P, Wein AJ. The Overactive Bladder: A Widespread and Treatable Condition. Erik Sparre Medical AB; 1998.

37. Characteristic Symptoms of OAB
Frequency
and
Urgency
Urge incontinence
Bladder pressure greater than urethral pressure
The characteristic symptoms of OAB are urinary frequency and urgency, with or without urge incontinence.
Urinary incontinence occurs when, involuntarily, the bladder pressure is greater than the urethral pressure.

38. Treatment: Lifestyle Changes
Avoid Bladder Irritants
Caffeine
Alcohol
Chocolate
Cigarettes
Acidic/Spicy foods

39. Treatment: Lifestyle Changes
Fluid Management:Avoid Excess intake
Drink 6-8 cups of fluids/day
Drink throughout day instead of “binge”
Drink most of fluid in day and afternoon
Avoid excessive restriction: concentrated urine

40. Treatment: Lifestyle Changes
Evaluate contributing Factors:
Medications
Avoid Constipation: Add Fiber to Diet
Obesity

41. Treatment: Lifestyle Changes
Medications affect Bladder Function by:
Decreasing Bladder Contractility
Increasing Bladder Contractility
Increasing Urethral Sphincter Tone
Decreasing Urethral Sphincter Tone

42. Treatment: Lifestyle Changes
Medications that Decrease Bladder Contractility
Anticholinergics
Beta-adrenergic Agonists
Calcium Channel Blockers
Alcohol (Also act as ADH inhibitor)
Antihistamines, sedatives, narcotics
Antidepressants
Antipsychotics

43. Treatment: Lifestyle Changes
Medications that increase detrussor irritability/diuresis
Diuretics
Caffeine
Alcohol

44. Treatment: Lifestyle Changes
Medications increase Urethral Sphincter Tone:
Alpha-Adrenergic Agonists
Amphetamines
Tricyclic Antidepressants

45. Treatment: Lifestyle Changes
Medications that Decrease Urethral Sphincter Tone:
Alpha-Adrenergic Blockers

46. Behavioral Modification
Timed voiding
Education
Behavioral Modification
Pelvic floor exercises
Delayed voiding
Various forms of behavioral modification can be helpful in the management of OAB.
Useful strategies for behavioral modification include patient education, timed or delayed voiding, and positive reinforcement of any changes made.
Pelvic floor exercises have been found useful for women, primarily those with stress urinary incontinence.
Reinforcement

47. Pelvic Floor Excercises
Self management program utilizing the Kegel technique or pelvic muscle exercises
May not see an improvement in bladder control for up to 3 to 6 weeks
May be improved with Biofeedback or Electical Stimulation

48. Bladder Retraining
Best with management of urinary frequency and urgency
Goal is to trick the bladder into thinking that it is always empty in an effort to regain voluntary control over bladder emptying.

49. When the Urge Strikes! Stop and stay still
Squeeze pelvic floor muscles
Relax rest of body
Concentrate on suppressing urge
Wait until the urge subsides
Walk to bathroom at normal pace

50. Limitations of Behavior and Lifestyle Changes
Require motivation in both patient and Provider
Success depends on intensity of program
High cost in terms of Provider time

51. Treatments for Over Active Bladder
Behavioral Therapy
Pelvic Floor Rehabilitation (Kegels)
Biofeedback
Electrical Stimulation
Neuromodulation (Interstim, Tibial Nerve Stimulation)
Botox Bladder injections
Medications

52. Medications for Over Active Bladder
Tolterodine
Oxybutynin (oral and Patch)
Darifenacin
Troposium
Solifenacin

53. Neurotransmitter Receptors
Cholinergic
Receptors
Adrenergic
Receptors
Nicotinic
Muscarinic
α-Adrenergic
β-Adrenergic
Both cholinergic and adrenergic receptors are involved in the regulation of micturition in humans.
Acetylcholine liberated from cholinergic nerves acts through muscarinic receptors to serve as a major mediator of the voiding response. Five distinct subtypes of muscarinic receptors, M1 through M5, have been identified in humans.
Although -adrenergic receptors do not appear to be involved in bladder control in normal individuals, their function may be altered in pathologic states and may facilitate contraction in patients with overactive bladder.
The -adrenergic receptors may be involved in relaxation of the human detrusor muscle.
Subtypes
M1, M2, M3, M4, M5
Adapted from Wein AJ. Exp Opin Invest Drugs. 2001;10:65-83.

54. Muscarinic Receptor Distribution
M1 : Neural Tissue
M2: Detrussor, Cardiac
M3: Detrussor, Salivary Glands and Bowel
M4: Cerbral Cortex, Lungs

55. Why Treat OAB with Antimuscarinics
Detrusor contraction in the normal bladder is primarily mediated via muscarinic receptors
release acetylcholine from cholinergic nerves
stimulation of muscarinic receptors on the detrusor smooth muscle

56. Clinical Effects of Antimuscarinic Therapy
Stabilizing effect on bladder (detrusor) muscle
Diminishes frequency of involuntary bladder contractions
Increases functional bladder capacity
Delays initial urge to void

57. Considerations in Choosing Anticholinergic Medications
Provides efficacy by inhibiting involuntary bladder contractions
Does not prevent normal micturitions
Is selective for the bladder over other organs, resulting in reduced side effects and improved tolerability
Provides clinical effectiveness—the optimal balance of efficacy, tolerability, and compliance/persistency

58. Distribution of Muscarinic Receptors in Target Organs of the Parasympathetic Nervous System
Iris/Ciliary Body = Blurred Vision
CNS
Lacrimal Gland = Dry Eyes
Dizziness
Somnolence
Impaired Memory & Cognition
Salivary Glands = Dry Mouth
Heart = Tachycardia
Gall Bladder
Stomach = Dyspepsia
Muscarinic receptors are widely distributed throughout the body. In addition to the bladder, these receptors are located in a variety of organs of the parasympathetic nervous system, as well as in the CNS.
The distribution of muscarinic receptors helps to explain the side effects associated with antimuscarinic drugs.
Common CNS side effects are dizziness, somnolence, and impaired memory and cognition. Effects at the iris or ciliary body can lead to blurred vision, whereas effects at the lacrimal gland may cause dry eyes. Inhibition of salivary secretion leads to dry mouth. Cardiac effects may take the form of tachycardia. Inhibition of muscarinic receptors may also be associated with effects in the stomach, or dyspepsia, and colon, or constipation.
Colon = Constipation
Muscarinic receptors are also located in the CNS.
Bladder (detrusor muscle)
Adapted from Abrams P, Wein AJ. The Overactive Bladder: A Widespread and Treatable Condition. Erik Sparre Medical AB; 1998.

59. Contraindications for Anticholinergics
Renal Failure
Hepatic Failure
Narrow Angle Gluacoma
Gastric Retention
History of an Allergic Reaction

60. Medication Failures Tolerability of side effects Lack of efficacy
High rate of noncompliance

61. Drug Therapy Persistence is Poor Among OAB Patients
Prescription persistency rates of OAB medications among patients new to market (n=21,362)
20%
40%
60%
80%
100%
56% of patients chose not to refill their prescription a second time
Only 15% of patients continued with their therapy through the first year
Source: The 2002 Gallup Study of the Market for Prescription Incontinence Medication. Princeton, NJ: Multi-Sponsor Surveys, Inc 2002

62. InterStim Therapy Sacral Nerve Stimulation for Urinary Control
Sacral nerve stimulation provides an effective alternative for voiding dysfunction patients who have not been helped- or could not tolerate- more conventional treatments, including pharmacotherapy.

63. InterStim® Therapy
Utilizes mild electrical pulses to the nerves associated with voiding function. Through neurostimulation, significantly improved or normal voiding is restored.
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64. History of Sacral Nerve Stimulation
1981 – Department of Urology, University of California at San Francisco initiated clinical program.
– Multi-center trial conducted by Urosystems, Inc.
1994 – Medtronic CE mark (approval to market in Europe) for InterStim Therapy in Europe for treatment of urge incontinence, retention and urgency-frequency.
September 1997 – FDA grants Medtronic approval of the InterStim System for treatment of urge incontinence in the US.
April FDA approval of the InterStim System for treatment of symptoms of urgency-frequency and urinary retention.
September 2002 – FDA approval of tined lead
August 2005 – Over 21,000 patients implanted worldwide

65. Who Can Benefit from InterStim Therapy?
Patients whose symptoms did not improve with more conventional treatments, such as medications
Patients with non-obstructive urinary retention
Patients with symptoms of overactive bladder, including urinary urge incontinence and urgency-frequency
Patients who cannot tolerate the side effects from medications

66. Benefits of InterStim Therapy
Effective Treatment in properly screened patients
Safe
Reversible
Does not preclude use of alternative treatments

67. Test Stimulation Procedure
A test is done prior to implant to determine how a patient will respond to the implanted device
Performed in the office or surgery center
A lead is surgically implanted near the S3 nerve
Lead is connected to an external device worn on the patient’s belt for a period of 3-7 days
Patient will record his/her voiding behavior in a diary

68. Test Stimulation Procedure
Locate & identify sacral nerves
Verify neural integrity
Allow the patient to feel the stimulation
Assess viability of sacral nerve stimulation on voiding behavior (goal is efficacy > 50% improvement in symptoms)
Help physician & patient make an informed choice about the long-term therapeutic value
The test stimulation phase is conducted to assess a patient’s functional response to SNS.
Note: Other than test stimulation, there are no pretreatment tests — including urodynamics — that can help to predict the outcome of surgery.

69. Test Stimulation Procedure Video
Test Stimulation (click to start and pause video)
[Test Stimulation, Slides 24-32]
After finding the bony landmarks, the foramen needle is inserted.
Then, using the foramen needle and a test stimulator, a test is done to assess sensory and/or motor responses of the sacral nerves.

70. Implant Procedure
After successful test stimulation, the physician may implant the InterStim System
A pocket is typically created for the neurostimulator in the upper buttock

71. Tined Lead
Model #3889 shown, Model #3093 not shown

72. Using the Tined Lead with the Lead Introducer
(CLICK ON THE PICTURE TO BEGIN THE VIDEO, CLICK CONTINUE & RESUME IF PROMPTED)
If the animation takes too long to download, you can find the same graphic
On the tined lead CD.

73. Contraindications to Interstim Therapy
Failure to respond by more than 50% to test stimulation
Outlet Obstruction
Patient without mental capacity to manage device
Bladder Cancer

74. Patient Programmer
Patient is given a programmer to control the settings on their own without visiting his/her physician or nurse
Allows patient to turn the device on and off, and adjust the levels of stimulation within physician-set limits

75. Clinical Study Overview
Multi-center randomized, prospective study*
23 centers: 9 European & 14 North American
581 patients (1993 – 1998)
Measurements:
Urge incontinence
Number of leaking episodes /day
Severity of leaking episodes
Number of pads/diapers replaced/day
Urgency-frequency
Number of voids/day
Volume voided/void
Degree of urgency prior to void
Retention
Volume per catheterization
Success was defined as a minimum of 50% improvement in at least one primary diary variable as compared to baseline. This same definition was used for qualifying after test stimulation but also to define clinical success after randomization.
This 50% improvement has been chosen in other studies as well (behavior/ biofeedback training; NIH studies) and has been accepted by the NIH and AHCPR as a standardized measure. For this reason also in this study a 50% improvement in symptoms was chosen.
Study initiated by Medtronic in December 1993 using the traditional implantation procedure (Staged Implant was not performed during this study; tined lead was not available for this study)
Included voiding dysfunctions of: urge incontinence (184 patients), retention (177 patients), urgency/frequency (220 patients).
Urge incontinence indication approved for market clearance on September 29, 1997 by U.S. Food & Drug Administration.
Urgency/frequency and retention indications approved for market clearance on April 15, 1999 by U.S. Food & Drug Administration.
Data (MDT-103):
* Staged Implant was not performed during this study

76. Efficacy: Overactive Bladder
Data (MDT-103):

77. Efficacy: Urinary Retention
Data (MDT-103):

78. Implantation: Ranking of Adverse Events in First 12 Months Post-implant
Pain at neurostimulator site 15.3%
New pain 9.0%
Suspected lead migration 8.4%
Infection 6.1%
Transient electric shock 5.5%
Pain at lead site 5.4%
Adverse change in bowel function 3.0%
Note: Additional events occurred – each less than 2.0%
Additional adverse events include technical problems (1.7%); suspected device problem (1.6%); change in menstrual cycle (1.0%); Adverse change in voiding function (0.6%); persistent skin irritation (0.5%); suspected nerve injury (0.5%); device rejection (0.5%).
Overall surgical revision rate at 12 months = 29%.
No reports of serious adverse device effects or permanent injury associated with the devices or the use of sacral nerve stimulation.
At database closure, 9% of reported events were unresolved.
Data (MDT-103):

79. InterStim® Therapy: Healthcare Utilization 1 year Before & After Implant
Kaiser Permanente® Healthcare System1
After one year 73% of patients indicated an improvement of 50% or greater
Outpatient visits and costs were reduced by 73%
Annual drug expenditures were reduced by 30%
N=65 patients
Pre-Implant Mean
Post Implant Mean
Mean Change
P Value
Voiding Related Diagnostic & Therapeutic Procedures
1.03
0.06
-1.0 procedures
<0.0001
Urinary Tract Infections
0.43
0.24
-0.19 UTIs
0.0959
Outpatient Visits
3.02
0.82
-2.3 visits
Outpatient Costs
$994
$265
-$729
Procedure Costs
$655
$59
-$596
Drug Expenditures
$693
$483
-$210
0.021
Aboseif, S. et al. Sacral Neuromodulation: Cost Considerations and Clinical Benefits. Manuscript Pending Acceptance. 2006
Medtronic-Confidential

80. Quality of Life Medtronic-Confidential
Patients implanted with InterStim System reported significantly improved ratings (p < ) in health-related quality of life (HRQOL) measures.1
The largest gain was noted in the subject’s perceived ability to increase their level of work performance or other daily activity. 1
An improvement of 10% to 40% in Beck Depression Inventory scores has been shown in urge incontinent patients.2
Improved results in both (HRQOL & depression) have been seen at three months and sustained for a 12-month period of follow-up.1
1 Das, A.K. et al. Improvement in Depression and Health-Related Quality of Life After Sacral Nerve Stimulation Therapy for Treatment of Voiding Dysfunction. Urology 64: 62-68, 2004.
2. Shaker, H.S. and Hassouna, M. Sacral Nerve Root Modulation: An Effective Treatment for Refractory Urge Incontinence. J Urol, 159: 1516, 1998
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81. InterStim Therapy Patients with no daily leakage episodes2
Patient Selection: Who Benefits Most?
Patients who are most likely to discontinue drug therapy may have the best chance for remaining completely dry
Adjusted Odds Ratio of age as a predictor of treatment drug discontinuation1
InterStim Therapy Patients with no daily leakage episodes2 .
(referent)
Campbell, U.B, Stang, P, Barron, R, Galt Associates, Inc., Allergan, Inc. Survey Assessment of Compliance and Satisfaction with Treatment for Urinary Incontinence. Poster Presentation, ICS Conference, 2005
Amundsen, C.L. et al. Sacral Neuromodulation for Intractable Urge Incontinence: Are There Factors Associated With Cure? Urology 66:
Medtronic-Confidential

82. Summary
Patients are more often prescribed medical therapy and polypharmacy before further treatment options, such as InterStim Therapy, are discussed
Because of the challenging compliance issues associated with medical management, patients may be placed in a cycle of being a “perpetual new patient” often discontinuing the healthcare system or accepting their condition before InterStim Therapy is presented to them
Randomized controlled trials may confirm long term results vs. more conservative treatments
InterStim Therapy is an effective treatment option in the treatment of voiding dysfunction, offering not only sustained results, but may also provide significant economic & quality of life considerations to payors and patients
Medtronic-Confidential