1. Anders Mellgren, MD, PhD, FACS, FASCRS Clinical Professor of Surgery Division of Colon & Rectal Surgery University of Minnesota Director, Pelvic Floor Center Colon & Rectal Surgery Associates Treatment of Fecal Incontinence with SNM

2. Disclosures MedtronicMedtronic American Medical SystemsAmerican Medical Systems HitachiHitachi Q-Med/ Oceana/ SalixQ-Med/ Oceana/ Salix ToraxTorax UroplastyUroplasty

3. Treatment Options Fecal Incontinence Traditional treatment modalitiesTraditional treatment modalities –Medication / biofeedback –Sphincteroplasty –Colostomy New treatment modalitiesNew treatment modalities –Sacral nerve stimulation –Injectable and implanta agents –Artificial anal sphincter Treatment modalities at the horizonTreatment modalities at the horizon

4. SNM for Fecal Incontinence Matzel et al., Lancet, 1995, 346; 1124-7

5. Copenhagen Prof. Christiansen London Prof. Kamm/ Prof. Nicholls Maastricht Prof. Baeten Vienna Dr. Rosen Terrassa Dr. Rius Erlangen Dr. Matzel Stockholm Dr. Mellgren Minneapolis Dr. Madoff MDT-301

6. 0,8 1,7 1,50 0,50 2,4 14 0 4 8 12 BaselineScreening3M6M12M24M MDT 301 Lancet 2004;363:1270-6

7. 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% Patients 24 m36 m48 m60 m12 mscreeningbaseline Not at all >15 min 5-15 min 1-5 min <1 min Postpone Defecation MDT 301 Lancet 2004;363:1270-6

8. 1 2 3 4 5 Baseline Last FU Scale Score Lifestyle Coping/ Behaviour Depression/ Self Perception Embarrassment p < 0.0001 FI Quality of Life MDT 301 Lancet 2004;363:1270-6

9. Conclusions MDT 301 Effective in improving symptoms and QoLEffective in improving symptoms and QoL Effect not only on anal sphinctersEffect not only on anal sphincters Patient selection by test stimulationPatient selection by test stimulation –Highly predictive Lancet 2004;363:1270-6

10. Sacral Nerve Modulation European approvalEuropean approval Several studiesSeveral studies 50-80% success rate50-80% success rate USAUSA Multicenter trial (IDE study)Multicenter trial (IDE study)

11. Prospective Multicenter Trial 133 patients (120 implanted)133 patients (120 implanted) Chronic fecal incontinenceChronic fecal incontinence ≥2 incontinent episodes / week≥2 incontinent episodes / week 5 year follow-up5 year follow-up

12. Incontinent Episodes / Week Prospective Multicenter Trial Baseline n = 120 3 Months n = 113 6 Months n = 107 12 Months n = 106 24 Months n = 72 36 Months n = 77 Wexner et al, Ann Surg 2010; 251: 441-9 Mellgren et al, DCR 2011;54:1065-75

13. Success Rate at 36 Months Prospective Multicenter Trial 59% 79% 86% Modified Worst Case Analysis n = 120 Last Observation Carried Forward Analysis n = 120 Completers Analysis n = 77 p = 0.0548 p < 0.0001 Mellgren et al, DCR 2011;54:1065-75

14. Improvement in Incontinent Episodes Prospective Multicenter Trial 3 Months n = 113 6 Months n = 107 12 Months n = 106 24 Months n = 72 36 Months n = 77 Mellgren et al, DCR 2011;54:1065-75

15. p-value < 0.0001 for all follow-ups Fecal Incontinence Quality of Life Prospective Multicenter Trial Baseline n = 119 3 Months n = 116 6 Months n = 110 12 Months n = 107 24 Months n = 73 36 Months n = 80 X Lifestyle Coping/Behavior Depression/Self-Perception Embarrassment Mellgren et al, DCR 2011;54:1065-75

16. Device & Therapy Related AEs Prospective Multicenter Trial Implant site pain 28%Implant site pain 28% Paresthesia 15%Paresthesia 15% Change in sensation of stimulation 12%Change in sensation of stimulation 12% Implant site infection 10%Implant site infection 10% Mellgren et al, DCR 2011;54:1065-75

17. Summary Prospective Multicenter Trial High success rateHigh success rate Few severe adverse eventsFew severe adverse events Requires continued follow-up and interestRequires continued follow-up and interest FDA approval March 2011FDA approval March 2011

18. Issues for Discussion Method of actionMethod of action Long-term efficacyLong-term efficacy Patients with sphincter injuryPatients with sphincter injury

19. Method of Action Anorectal Manometry Altomare et al, DCR 2009

20. Method of Action Other Effects Reduction of antegrade transport from the ascending colonReduction of antegrade transport from the ascending colon Increase of rectal capacityIncrease of rectal capacity Changes in rectal sensitivityChanges in rectal sensitivity Enhanced activation of midbrain regionsEnhanced activation of midbrain regions Michelsen et al, Br J Surg 2008 Carrington et al, Colorectal Disease 2011 Kenefick, Br J Surg 2003

21. 0 2 4 6 8 10 12 14 16 01224364860728496108120132144156168 Time after Implant [month] # of FI episodes / week Melenhorst, Colorectal Dis 2007 Matzel, Colorectal Dis 2009 Dudding, BrJSurg 2008 Altomare, Dis Colon Rectum 2009 134 9 89 76 5333 15 6 8 4 4 3 2 2 2 50 70 50 48Screening Long-term Success Rate SNM

22. SNM in Patients with Sphincter Injury

23. Summary Sacral Nerve Modulation for FI High success rate, which seems to be sustained long-termHigh success rate, which seems to be sustained long-term Works also in patients with sphincter defectsWorks also in patients with sphincter defects Benign adverse event profileBenign adverse event profile

24. Current Role of SNM Management of Fecal Incontinence Clinical evaluationClinical evaluation –Treat underlying correctable factors –Physiologic evaluation Non-surgical treatmentNon-surgical treatment –Medication (loperamid) –Biofeedback SNM/ surgery/ injectionSNM/ surgery/ injection

25. Evaluation EAUS ± other tests Failed conservative treatment Sphincterdefect SNSInjectables ColostomyACE Persistent fecal incontinence Sphincteroplasty Novel therapies: PTNS Magnetic sphincter Slings ABS Stim. graciloplasty First line Second line ICI 2012 No sphincter defect

26. Current Status of SNM for FI (USA) FDA approved March 2011FDA approved March 2011 Trained > 200 surgeonsTrained > 200 surgeons Increasing useIncreasing use

27. Conclusions Treatment of Fecal Incontinence with SNM High success rate and benign morbidity profileHigh success rate and benign morbidity profile First line treatment when conservative treatment failsFirst line treatment when conservative treatment fails Combination of therapies?Combination of therapies?