Nerve Stimulation Nerve Stimulation Therapies for Bowel and Therapies for Bowel and

Bladder ContinenceBladder Continence

R. Keith Huffaker, MD, MBA, FACOGR. Keith Huffaker, MD, MBA, FACOG

Quillen/ETSU Center for Pelvic Quillen/ETSU Center for Pelvic Surgery and UrogynecologySurgery and Urogynecology

ObjectivesObjectives

• Sacral nerve stimulation (SNS)Sacral nerve stimulation (SNS)– InterStimInterStim– DiagnosesDiagnoses

• Percutaneous tibial nerve stimulation Percutaneous tibial nerve stimulation (PTNS)(PTNS)– Urgent PCUrgent PC– DiagnosesDiagnoses

Where do InterStim and Urgent PC Where do InterStim and Urgent PC fit?fit?

Interstim – Sacral Interstim – Sacral NeuromodulationNeuromodulation

IndicationsIndications• Urinary FrequencyUrinary Frequency

• Urinary UrgencyUrinary Urgency

• Urge Urinary Urge Urinary IncontinenceIncontinence

• Urinary Retention / Urinary Retention / Incomplete Bladder Incomplete Bladder EmptyingEmptying

• Fecal IncontinenceFecal Incontinence

• Not for SUINot for SUI

Micturition and Storage Micturition and Storage ReflexesReflexes

Leng & Chancellor UNA 2005

It’s simply the It’s simply the muscles or the muscles or the nervesnerves

Where Medications

Work

Efferent messages tell muscles to work.

Medication may help muscle comply better

Where InterStim works

Sensory Messages (Afferent) tell the brain what is happening with the bladder and other voiding components

InterStim modulates incorrect messages.

Also has some effect on muscles/motor

InterStim: consider after twomedications fail. Unlikely third or fourth will work.

InterStim Pre-test InterStim Pre-test RequirementsRequirements• Patient has had condition for Patient has had condition for > 1 year> 1 year• Stress incontinence has been eliminatedStress incontinence has been eliminated as as

major urinary complaintmajor urinary complaint• Patient Patient failedfailed conventional therapy: conventional therapy:

– Behavior modificationsBehavior modifications– Two medication failuresTwo medication failures– Cannot comply with other treatment option (I.e. self-Cannot comply with other treatment option (I.e. self-

cath)cath)

• Can complete urinary diary and use deviceCan complete urinary diary and use device• Patient has improvement of 50% or > during Patient has improvement of 50% or > during

testtest

Mechanism of ActionMechanism of Action

• Mechanism of action for SNS is Mechanism of action for SNS is not fully not fully understoodunderstood at this time - many theories at this time - many theories exist.exist.

• Generally agreed that stimulation of the Generally agreed that stimulation of the sacral nerves sacral nerves modulates the neural modulates the neural reflexesreflexes that influence the bladder, that influence the bladder, sphincter and pelvic floor that sphincter and pelvic floor that control/influence voiding. (Afferent control/influence voiding. (Afferent pathways)pathways) Reference: Chancellor MB, Chartier-Kastler EJ. Principles of

sacral nerve stimulation (SNS) for the treatment of bladder and urethral sphincter dysfunctions. International Neuromodulation Society 2000; 3: 15-26.

But is it really But is it really doing doing anything?anything?

• Dasgupta and Fowler. Changes in brain activity Dasgupta and Fowler. Changes in brain activity following sacral neuromodulation for urinary following sacral neuromodulation for urinary retention.J Urol. 2005 Dec;174(6):2268-72. retention.J Urol. 2005 Dec;174(6):2268-72.

• Therapy consists of 2 steps:Therapy consists of 2 steps:

1.1. Test stimulationTest stimulation procedure procedure – – allows trial of InterStim Therapyallows trial of InterStim Therapy

-simple (-simple (30-45) minutes30-45) minutes-done in -done in office (PNE)office (PNE) or or

outpatientoutpatient room (PNE or Stage room (PNE or Stage I) I)

--test for a ½ to 1 week --test for a ½ to 1 week -percutaneous wire-percutaneous wire-external pulse generator -external pulse generator -voiding diary-voiding diary

2. Implantation of device 2. Implantation of device --full implant--full implant--Stage II--Stage II--both steps target S3 foramen and --both steps target S3 foramen and nervesnerves

After Test ProcedureAfter Test Procedure

• Voiding diaryVoiding diary– 50% improvement required for implantation50% improvement required for implantation– Implantation is not required if you choose not to do soImplantation is not required if you choose not to do so

• Second stepSecond step– PNE wires removed in office, orPNE wires removed in office, or– OR for staged approachOR for staged approach

•Place neurostimulatorPlace neurostimulator

•Remove leadRemove lead

Implant ProcedureImplant Procedure• Patients with a Patients with a

successful test successful test stimulation go on to stimulation go on to implantation of the implantation of the internal pulse internal pulse generator. (50%)generator. (50%)

• A pocket is typically A pocket is typically created for the created for the neurostimulator in neurostimulator in the upper buttock.the upper buttock.

Tined LeadTined Lead

Patient ProgrammerPatient Programmer Physician ProgrammerPhysician Programmer

Clinical Study OverviewClinical Study Overview

• Multi-center randomized, prospective studyMulti-center randomized, prospective study**– 23 centers: 9 European & 14 North American23 centers: 9 European & 14 North American– 581 patients (1993 – 1998)581 patients (1993 – 1998)

• Measurements:Measurements:– Urge incontinenceUrge incontinence

• Number of leaking episodes /day Number of leaking episodes /day • Severity of leaking episodesSeverity of leaking episodes• Number of pads/diapers replaced/day Number of pads/diapers replaced/day

– Urgency-frequencyUrgency-frequency• Number of voids/dayNumber of voids/day• Volume voided/voidVolume voided/void• Degree of urgency prior to voidDegree of urgency prior to void

– RetentionRetention• Volume per catheterizationVolume per catheterization

* Staged Implant was not performed during this study

Efficacy: Overactive Efficacy: Overactive BladderBladder

Efficacy: Urinary RetentionEfficacy: Urinary Retention

Implantation:Implantation:Ranking of Adverse Events in Ranking of Adverse Events in First 12 Months Post-implantFirst 12 Months Post-implant

• Pain at neurostimulator sitePain at neurostimulator site 15.3%15.3%

• New painNew pain 9.0%9.0%

• Suspected lead migrationSuspected lead migration 8.4%8.4%

• InfectionInfection 6.1%6.1%

• Transient electric shockTransient electric shock 5.5%5.5%

• Pain at lead sitePain at lead site 5.4%5.4%

• Adverse change in bowel functionAdverse change in bowel function 3.0%3.0%

Note: Additional events occurred – each less than 2.0%Note: Additional events occurred – each less than 2.0%

Chan and Tjandra. Sacral Nerve Stimulation for Fecal Incontinence: External Anal Sphincter Defect vs. Intact Anal Sphincter. Diseases of the Colon and Rectum:2008. • Prospective studyProspective study

• External anal sphincter defect, n=21External anal sphincter defect, n=21

• External anal sphincter intact, n=32External anal sphincter intact, n=32

• 3,6,12mo f/u 3,6,12mo f/u – Anorectal physiologyAnorectal physiology– Wexner’s scoreWexner’s score– Bowel diaryBowel diary– QOL Q’sQOL Q’s

• All 53 benefited from SNSAll 53 benefited from SNS

• EAS defects: Weekly incont. episodes EAS defects: Weekly incont. episodes decreased from 13.8 to 5 at 12 mos.decreased from 13.8 to 5 at 12 mos.

• EAS intact 6.7 to 2EAS intact 6.7 to 2

• QOL scores improved for both groupsQOL scores improved for both groups

• +/- pudendal neuropathy irrelevant+/- pudendal neuropathy irrelevant

• Size of EAS defect did not matter up to Size of EAS defect did not matter up to 120 degrees120 degrees

LeRoi, et al. Efficacy of Sacral Nerve Stimulation for Fecal IncontinenceResults of a Multicenter Double-Blind Crossover Study. Annals of Surgery:2005.

• n=27 (most were women)n=27 (most were women)

• SNS implantedSNS implanted

• Double-blind crossover designDouble-blind crossover design

• Randomized to on or off for one Randomized to on or off for one month periodsmonth periods

• Pt then chose the period of preference Pt then chose the period of preference not knowing whether was actually on not knowing whether was actually on or offor off

• Placed in preferred mode for 3 monthsPlaced in preferred mode for 3 months

• Outcome measuresOutcome measures– FIFI– Fecal urgencyFecal urgency– Delay in postponing defecationDelay in postponing defecation– ManometryManometry– QOLQOL– Etc.Etc.

• Significant improvement in all when Significant improvement in all when onon

• Clinical benefit not due to placeboClinical benefit not due to placebo

Diagnosis Procedure Success Implant Implant success

IE SNS PNE No No NA

IE SNS PNE No No NA

UUI SNS PNE Yes No NA

IE and UUI SNS PNE Yes Yes Yes

UUI SNS PNE Yes Yes Yes

UUI and FI SNS PNE Yes Yes Yes

UUI SNS PNE Yes Yes Yes

UUI SNS PNE Yes Yes Yes

IE SNS PNE No No NA

IE and UUI SNS PNE Yes Yes Yes

UUI SNS PNE Yes Yes Yes

UUI SNS PNE Yes Yes Yes

IE and UUI SNS PNE Yes Yes Yes

UUI SNS PNE Yes Yes Yes

IE and MUI SNS PNE Yes Yes Yes

UUI and FI SNS PNE Yes Yes Yes

MUI SNS PNE Yes Yes Yes

IE and FI SNS PNE Yes Yes Yes

UUI SNS PNE Yes Yes Yes

IE and UUI SNS PNE Yes Yes Yes

RKH SNS Results

IE=incomplete bladder emptying; UUI=urge urinary incontinence;

FI=fecal incontinence; MUI=mixed urinary incontinence

Interstim Bottom LineInterstim Bottom Line

• Interstim is FDA approved forInterstim is FDA approved for– refractory urgency and frequencyrefractory urgency and frequency– urge incontinenceurge incontinence– incomplete bladder emptying incomplete bladder emptying – fecal incontinencefecal incontinence– Not for pain (PBS/BPS/IC)Not for pain (PBS/BPS/IC)

• Effective therapy with intermediate long-Effective therapy with intermediate long-term follow-up. term follow-up.

• Support is criticalSupport is critical

An Option Between An Option Between Conservative and Conservative and Surgical TreatmentsSurgical Treatments

Simple, Simple, Office-based Office-based Neuromodulation Neuromodulation with Urgent® PCwith Urgent® PC

Urgent® PC

What is PTNS?What is PTNS?

• Defined in a variety of ways:Defined in a variety of ways:– Percutaneous Tibial Nerve StimulationPercutaneous Tibial Nerve Stimulation– Posterior Tibial Nerve StimulationPosterior Tibial Nerve Stimulation– Posterior Tibial NeurostimulationPosterior Tibial Neurostimulation

• Example: New CPT® code 64566 Example: New CPT® code 64566 ““Posterior tibial neurostimulation - Posterior tibial neurostimulation - percutaneous electrode, single percutaneous electrode, single treatment, includes programming”treatment, includes programming”

Potential Urgent PC PatientsPotential Urgent PC Patients

UrgentUrgent®® PC PC• Easy to administer in twelve 30 minute Easy to administer in twelve 30 minute

sessions with maintenance therapy sessions with maintenance therapy variablevariable

• Effective – Approximately 2/3 of Effective – Approximately 2/3 of patients report a reduction in their patients report a reduction in their symptomssymptoms

• May work even if other treatments May work even if other treatments have failedhave failed

• Low risk – Most common side-effects Low risk – Most common side-effects include transient mild pain or skin include transient mild pain or skin inflammation at or near the stimulation inflammation at or near the stimulation sitesite

Treatment with UrgentTreatment with Urgent®® PC PC• Stimulation Stimulation

delivered via a 34 delivered via a 34 ga. needle electrodega. needle electrode

• Needle electrode Needle electrode inserted above inserted above medial malleolusmedial malleolus

• The needle The needle electrode is electrode is connected to a connected to a battery-powered battery-powered stimulatorstimulator

•Provides Percutaneous Tibial Nerve Stimulation (PTNS)

Treatment with UrgentTreatment with Urgent®® PC PC• Impulse travels from the ankle Impulse travels from the ankle

along the tibial nerve to the along the tibial nerve to the sacral nervessacral nerves

UrgentUrgent®® PC Neuromodulation PC Neuromodulation SystemSystem

Office-based TreatmentOffice-based Treatment• Patient is clothed and comfortablePatient is clothed and comfortable

• May be administered by qualified May be administered by qualified staff, under physician supervisionstaff, under physician supervision

• Physician and staff Physician and staff can treat multiple can treat multiple patients at oncepatients at once

Treatment FrequencyTreatment Frequency• 12 weekly Urgent PC treatments12 weekly Urgent PC treatments

• Responders may need maintenance Responders may need maintenance treatments to sustain improvementstreatments to sustain improvements– Slowly increase time between Slowly increase time between

treatmentstreatments– If symptoms reappear or increase in If symptoms reappear or increase in

severity, return to last frequency to severity, return to last frequency to sustain reliefsustain relief

– In OrBIT study, treatment interval In OrBIT study, treatment interval increased to 24 days between increased to 24 days between treatments during months 6 – 12treatments during months 6 – 12

Urgent PC ContraindicationsUrgent PC Contraindications• Patients who are pregnant or planning to become pregnant Patients who are pregnant or planning to become pregnant

while using this productwhile using this product

• Patients with pacemakers or implantable defibrillatorsPatients with pacemakers or implantable defibrillators

• Patients prone to excessive bleedingPatients prone to excessive bleeding

• Patients with nerve damage that could impact either Patients with nerve damage that could impact either percutaneous tibial nerve or pelvic floor functionpercutaneous tibial nerve or pelvic floor function

• Not intended for intra-cardiac or Not intended for intra-cardiac or trans-thoracic usetrans-thoracic use

• Concurrent use of medical monitoring equipment during Concurrent use of medical monitoring equipment during stimulation is not recommendedstimulation is not recommended

• Not suitable for use in the presence of a flammable Not suitable for use in the presence of a flammable anesthetic mixture with air or with oxygen or nitrous oxideanesthetic mixture with air or with oxygen or nitrous oxide

PTNS Clinical EffectivenessPTNS Clinical Effectiveness• 30+ peer reviewed publications 30+ peer reviewed publications

demonstrate safety and efficacydemonstrate safety and efficacy– Reduce urgency, urge incontinence & Reduce urgency, urge incontinence &

frequencyfrequency– Significant objective and subjective Significant objective and subjective

improvementsimprovements– No serious adverse events or No serious adverse events or

side-effectsside-effects– Improved quality of lifeImproved quality of life– Objective urodynamic dataObjective urodynamic data– 2/3 of patients respond well2/3 of patients respond well

Meta-Analysis of 7 PTNS Meta-Analysis of 7 PTNS StudiesStudies

Martinson, M. (2008). Meta-Analysis of PTNS for Urinary Disorders. Sponsored by Uroplasty, Inc.

60 – 80% Response 60 – 80% Response

MacDiarmid, S., & Staskin, D. (2009). PTNS: A literature based assessment . Curr Bladder Dys , 4, 29-33.

PTNS compared to DrugPTNS compared to Drug• Patient perception of cure/improvement:Patient perception of cure/improvement:

80% in PTNS group; 55% in tolterodine LA group80% in PTNS group; 55% in tolterodine LA group

• Physician perception of cure/improvement:Physician perception of cure/improvement: 80% in PTNS group; 61% of tolterodine LA group 80% in PTNS group; 61% of tolterodine LA group

• Comparable reductions in voiding episodes and Comparable reductions in voiding episodes and urge incontinenceurge incontinence

• Side-effects:Side-effects: No serious adverse events were No serious adverse events were associated with either treatment. Constipation and associated with either treatment. Constipation and dry mouth reported more often in tolterodine LA dry mouth reported more often in tolterodine LA groupgroup

Peters, K.M., Leong, F.C., Shobeiri, S.A., MacDiarmid, S.A., Rovner, E.S., Wooldridge, L.S., et al. (2008). Randomized multicenter study comparing percutaneous tibial nerve stimulation with pharmaceutical therapy for the treatment of overactive bladder. Abstract, American Urologic Association, Annual Meeting, Orlando, FL.

PTNS Long-Term Follow-upPTNS Long-Term Follow-up• Retrospective analysis of 256 patients Retrospective analysis of 256 patients

(178 were treated for OAB symptoms)(178 were treated for OAB symptoms)

• Sixty percent (107/178) of patients with Sixty percent (107/178) of patients with OAB symptoms were respondersOAB symptoms were responders

• Results stable at three-year mean follow-Results stable at three-year mean follow-up when initial series was followed by up when initial series was followed by maintenance therapymaintenance therapy

• Only 10% of patients showed significant Only 10% of patients showed significant reduction of the obtained resultsreduction of the obtained results

Cappellano F., Finazzi Agro E., Giollo A., Petta F., Catanzaro M., Miano R., Germani S., Catanzaro F. (2006). Percutaneous tibial nerve stimulation (PTNS): results at long term follow-up. Abstract presented at the SIUD Congresso Nationale 2006, 27-30 September, Rome, Italy.

OrBIT – UPC vs. DetrolOrBIT – UPC vs. Detrol®® LA LA• Multicenter, RCTMulticenter, RCT

• 12 week phase12 week phase

• 12 month responder follow-up12 month responder follow-up

• 1:1 randomization (n=100)1:1 randomization (n=100)

• Physician and patient GRAPhysician and patient GRA

• Voiding diaries, QoL measuresVoiding diaries, QoL measures

OrBIT Results at 12 WeeksOrBIT Results at 12 Weeks

OrBIT Results at 12 WeeksOrBIT Results at 12 Weeks

OrBIT – Side EffectsOrBIT – Side Effects• Constipation reported less often in Constipation reported less often in

PTNS arm compared to drug arm PTNS arm compared to drug arm (p=0.04)(p=0.04)

• Dry mouth reported less often in Dry mouth reported less often in PTNS arm compared to drug arm PTNS arm compared to drug arm (p=0.0004)(p=0.0004)

• PTNS group reported pain, PTNS group reported pain, discomfort or redness at ankle discomfort or redness at ankle (assessed for PTNS group only)(assessed for PTNS group only)

OrBIT Results – Long-termOrBIT Results – Long-term• Statistically significant improvement Statistically significant improvement

sustained from 12 weeks thru 12 sustained from 12 weeks thru 12 monthsmonths– Frequency -2.8 voids/day Frequency -2.8 voids/day (p<0.001)(p<0.001)

– Nighttime voids -0.8 voids/night Nighttime voids -0.8 voids/night (p<0.05)(p<0.05)

– Urgency -3.7/day Urgency -3.7/day (p<0.01)(p<0.01)

– Voided volume +39 cc Voided volume +39 cc (p<0.05)(p<0.05)

– Incontinence episodes -1.6/day Incontinence episodes -1.6/day (p<0.001)(p<0.001)

– QOL measure QOL measure (p<0.01)(p<0.01)

• No serious adverse events or device No serious adverse events or device malfunctionsmalfunctions

OrBIT Results – Long-termOrBIT Results – Long-term

• Responders continued treatmentResponders continued treatment– 90% for 6 months90% for 6 months– 73% for 12 months73% for 12 months

• Sustained improvements at 12 Sustained improvements at 12 monthsmonths

OrBIT – Treatment IntervalOrBIT – Treatment Interval

Risks of TreatmentRisks of Treatment

• The risks of Urgent PC are lowThe risks of Urgent PC are low

• Side-effects include:Side-effects include:– Transient moderate pain at or near Transient moderate pain at or near

the stimulation sitethe stimulation site– Transient mild pain or skin Transient mild pain or skin

inflammation at or near the inflammation at or near the stimulation site stimulation site

– Transient mild bleeding at needle Transient mild bleeding at needle insertion siteinsertion site

Diagnosis Procedure Success

UUI PTNS Yes

UUI PTNS Yes

RKH PTNS Results

n=2; both successful

What’s Next for PTNSWhat’s Next for PTNS

• Shorter therapy protocolsShorter therapy protocols

• Determination of prolonged treatment Determination of prolonged treatment protocolsprotocols

• Fecal urgency and incontinenceFecal urgency and incontinence

• Constipation Constipation

• Incomplete bladder emptyingIncomplete bladder emptying

• Chronic pelvic painChronic pelvic pain

• Chronic non-bacterial prostatitis painChronic non-bacterial prostatitis pain

• Pediatric use for LUTSPediatric use for LUTS