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ABS Complications

Anal Slings-investigational

Similar to transvaginal tape or transobturator tape for UIDacron, mersilene, polyester, and teflon mesh, fascia lataW d i f ti i t t lWound infections, sinus tract, ulcerTreated with antibiotics or removalUsed in conjunction with tx for rectal prolapse

TRANSFORM StudyClinicalTrials.gov Identifier:

NCT01090739

TOPAS (AMS) sling for FIProspective, multiProspective, multi--center(12 sites)center(12 sites)

SingleSingle--arm, openarm, open--label, twolabel, two--stage, stage, adaptive study with one planned adaptive study with one planned interim analysis interim analysis

Primary outcome 14Primary outcome 14--day bowel day bowel diarydiary--50% reduction FI episodes50% reduction FI episodes

N=152N=152

The mesh sling placed via the The mesh sling placed via the transobturatortransobturator approachapproach

Mellgren A, et al. Am J Obstet Gynecol, 2015.

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Primary Primary OutcomeOutcome50% reduction in the number of FI episodes from baseline 50% reduction in the number of FI episodes from baseline to 12 months postto 12 months post--operatively on a 14 day bowel diary.operatively on a 14 day bowel diary.

Secondary OutcomesSecondary OutcomesDecrease in Fecal Incontinent Days and Urge EpisodesDecrease in Fecal Incontinent Days and Urge EpisodesDecrease in Fecal Incontinent Days and Urge EpisodesDecrease in Fecal Incontinent Days and Urge Episodes

Symptom Severity: Cleveland Clinic Incontinence ScoresSymptom Severity: Cleveland Clinic Incontinence Scores

Quality of Life: Fecal Incontinence Quality of Life (FIQOL)Quality of Life: Fecal Incontinence Quality of Life (FIQOL)

Safety Safety

SurgerySurgery

SurgerySurgery

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SurgerySurgery

Age (years) 59.6 ± 9.7

BMI (kg/m²) 27.8 ± 5.4

Ethnicity

White/Caucasian 137 (90.1%)

Black or African American 10 (6.6%)

American Indian/First Nations 0 (0%)

Asian 1 (0.7%)

Hispanic/Latina 3 (2.0%)

Native Hawaiian/Pacific Islander ( %)

DEMOGRAPHICS

Native Hawaiian/Pacific Islander 0 (0%)

Other 1 (0.7%)

Obstetric History

Parity 2.6 ± 1.4

# of vaginal deliveries 2.4 ± 1.5

Menopausal Status

Pre-menopausal 20 (13.2%)

Peri-menopausal 6 (3.9%)

Post-menopausal 126 (82.9%)

Continuous Variables are mean ± SD; Categorical variables are N (%)

SurgerySurgery

Mean surgical time = 33 minutes (range 11Mean surgical time = 33 minutes (range 11--71)71)

Mean EBL = 13 cc (range 0Mean EBL = 13 cc (range 0--50)50)

Mean hospital stay = 11 hours (2Mean hospital stay = 11 hours (2--57)57)

NO visceral injuries or perforationsNO visceral injuries or perforations

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Primary OutcomePrimary Outcome--12 months12 months

Sustained OutcomesSustained Outcomes--34 months34 months

Secondary OutcomesSecondary Outcomes

BaselineMedian (range)

12 mos. Median (range)

P value

CCIS (Wexner) 13.9 (mean) 9.6 (mean) < 0.001

FI Episodes per k

9.0 (2-40.5) 2.0 (0-40) < 0.001week

FI Incontinent Days 5.0 (1.5-7) 2.0 (0-7) < 0.001

FI with Urgency 2.0 (0-7) 0 (0-26) < 0.001

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Improvement in FIQOLImprovement in FIQOL

P<0.05 for all domains

Treatment Related Adverse EventsTreatment Related Adverse Events

Adverse Event Category Number of

Events Number of Patients

(% Patients)

Pelvic pain 47 41 (27.0%)

Infection 26 22 (14.5%)

Incision site infection 9 9 (5.9%)

Abscess 2 2 (1.3%)

Other infection problem 15 14 (9.2%)

Urinary problems 6 6 (3.9%)

Worsening urinary incontinence 2 2 (1.3%)

17 no treatment29 treated with medical therapyg y ( )

Other urinary problem 4 4 (2.6%)

Pelvic organ prolapse 8 6 (3.9%)

Pelvic organ prolapse (de novo) 4 3 (2.0%)

Pelvic organ prolapse (worsening) 4 3 (2.0%)

Bleeding 1 1 (0.7%)

Defecatory dysfunction 2 2 (1.3%)

Other 14 14 (9.2%)

Total 104 66 (43.4%)

NO mesh erosions or extrusions

py1 sciatica surgery

10 persistent at 1 year None classified as SAEs by FDA

standards

Refractory to multi-component treatment

Anal Sphincter Repair

Other procedures/surgical interventions

Surgical/Other Procedural Treatments for Fecal Incontinence

NeuromodulationArtificial sphincter

Anal Sling-investigational

Refractory to All

Colostomy

SECCAPosterior/Percutaneous Tibial

Nerve StimulationHyaluronate Sodium

Magnetic Anal Sphincter-invest, Myoblast-investigational

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Radiofrequency Therapy: SECCA®

SECCA® Efficacy Data

Long-term* (5 year) study, mean Wexner incontinence score improved from 14 to 8, p<0.0003

80% subjects had 50% improvement

N=19

O fOther studies limited by short-term follow-up and small sample sizes (N=8-50)

No comparative data

Main AEs rectal bleeding and pain

*Takahashi-Monroy et al, 2008

PTNS-targets sacral plexus

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Posterior Tibial Nerve Stimulation

Peripheral neuromodulation directed to L4-S3 nerve roots

Spleen 6 point in p pChinese acupuncture

OAB, UUI, pelvic/bladder OAB, UUI, pelvic/bladder pain, impotencepain, impotence

RCT with sham effective for OAB/Urge UI

PTNS

The largest prospective study including 115 patients with a median follow-up of 26 months (range, 12 – 42) reported 52% of patients achieving a ≥ 50% reduction in FI episodes as well as improving QOL*

First multi-center RCT (the CONtrol of Faecal Incontinence using Distal NeuromoulaTion [CONFIDeNT]) in the United Kingdom was recently published

This trial included 227 patients to evaluate the efficacy and costThis trial included 227 patients to evaluate the efficacy and cost-effectiveness of PTNS (n=115) comparing to sham electrical stimulation (n=112)

Interestingly, the study reported no difference between the PTNS and sham groups in efficacy at 12 weeks: 38% in PTNS versus 31% in sham achieving a ≥50% reduction in the number of FI episodes per week, adjusted ratio 1.28 (95%CI 0.72-2.28; p=0.40) **

*Hoturas et al, 2014; **Knowles, 2015

Non Animal Sodium Hyaluronate-NASHA Dx

DextranomerDextranomer microspheres microspheres and sodium hyaluronic acidand sodium hyaluronic acid

Identical to Deflux

Administered via anoscopeto the proximal anal canal

Out-patient setting

No anesthesia

Four 1ml blebs of Solesta

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Solesta: Pivotal Trial

Only large scale trial in the literature – injectable bulking agent vs. sham

206 patients13 sites in U.S. and EU13 sites in U.S. and EU

80% female80% female80% female80% female

Three part primary endpointSuperiority over sham at 6 monthsSuperiority over sham at 6 months

Threshold responder rate at 6 months Threshold responder rate at 6 months

Durability of effect to 12 months Durability of effect to 12 months

Graf et al, Lancet, 2011

Solesta Pivotal Trial: Results

All 3 success criteria were metResponder rates superior to sham at 6 monthsResponder rates superior to sham at 6 months

Above the predetermined thresholdAbove the predetermined threshold

Durability of effect out to 12 months: 57.4% ResponderDurability of effect out to 12 months: 57.4% Responder50

80

53.2%

30.7%

0

20

40

60

80

Solesta Shamrop

ort

ion

res

po

nd

ers 5

0(%

)

p=0.004

Most Common Related AEs - Solesta PatientsPivotal Study Through 18 Months

Preferred term Events % patients

Proctalgia 41 17.3

Injection site hemorrhage 18 8.1

Rectal hemorrhage 15 7.6

Pyrexia 14 6.6

Injection site pain 10 5.1

Diarrhea 10 4.1

Anal hemorrhage 9 4.1

Anorectal discomfort 8 4.1

Rectal discharge 7 3.6

Proctitis 5 2.5

Majority of AE’s were mild and self limited

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Magnetic Anal SphincterMagnetic Anal Sphincter--InvestigationalInvestigational

-Fenix™ -series of titanium beads with magnetic cores linked together with independent titanium wires -to defecate, the force generated by straining separates the beads to open up the anal canal -the technique of implantation is simple with no requirement of adjustments

18 subjects (15 women) underwent MAS, f/u 353-738 daysCCIS decreased from 17.5 (14-20) to 7.3 (0-12), all domains of FIQOL improved76% subjects ≥50% reduction FI episodes/w

Pakravan F, Helmes C . Dis Colon Rectum, 2015

Autologous Myoblast Injection-Investigational

Injection of autologous myoblast injection can potentially replace or repair damaged sphincter tissue and enhance function

Animal model studies being performed

Myogenic stem cell studies also being performedMyogenic stem cell studies also being performed

Carr et al, 2013, Carr et al, 2008, Frudinger etal, 2010, Montoya et al, 2015

Final Consideration

Fecal Diversion

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Fecal Diversion

Considered “last resort”

One case-control and two cohort studies

Results in improved QOL

More cost effective at 5 years than artificial AS and dynamic graciloplasty

Usually an end sigmoid colostomy without proctectomy (rectal stump))

Laparoscopic approach, safe and effectiveLaparoscopic approach, safe and effective

Colquhoun et al, 2006; Norton et al, 2005;Ludwig et al, 1996

Question

Treatments for fecal incontinence that are considered investigational include all of the following except:

A. Fenix titanium beads

B. Non-animal sodium hyaluronate

C. Posterior tibial nerve stimulation

D. TOPAS peri-anal sling

Question

Treatments for fecal incontinence that are considered investigational include all of the following except:

A. Fenix titanium beads

B. Non-animal sodium hyaluronate

C. Posterior tibial nerve stimulation

D. TOPAS peri-anal sling

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Conclusions

Cause of fecal incontinence is often multi-factorial

1st line treatment is… Education Education

Pelvic Floor Muscle ExercisesPelvic Floor Muscle Exercises

MedicationsMedications

Normalization Of Stool Consistency Normalization Of Stool Consistency

Bowel HabitsBowel Habits

Devices*Devices*

Surgery helpful for many women

Need to be able to discuss all options with patients and individualize care

Conclusions

Sphincteroplasty has reasonable shortSphincteroplasty has reasonable short--term but term but reduced longreduced long--term resultsterm results

Neuromodulation therapy helps those with refractory FI

Other therapies needed-recent data on devices; p ;need RCTs!

Individualization of treatment

Things could always be worse…….Things could always be worse…….

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Select ReferencesSelect References

National Institute for Health and Clinical Excellence (2007). National Institute for Health and Clinical Excellence (2007). FaecalFaecal Incontinence: Incontinence: The Management of The Management of FaecalFaecal Incontinence in Adults. Clinical guideline No. 49. Incontinence in Adults. Clinical guideline No. 49. NICE, LondonNICE, London

RemesRemes--Troche JM, Troche JM, RaoRao SSC. Neurophysiological testing in SSC. Neurophysiological testing in anorectalanorectal disorders. disorders. Expert Rev Expert Rev GastroenterolGastroenterol HepatolHepatol 2008;2:3232008;2:323--335335

OmotoshoOmotosho TB, Rogers RG. Evaluation and Treatment of Anal Incontinence, TB, Rogers RG. Evaluation and Treatment of Anal Incontinence, Constipation andConstipation and DefecatoryDefecatory DysfunctionDysfunction ObstetObstet GynecolGynecol ClinClin N AmN AmConstipation, and Constipation, and DefecatoryDefecatory Dysfunction. Dysfunction. ObstetObstet GynecolGynecol ClinClin N Am N Am 2009;36:6732009;36:673--697697

Hayden DM, Weiss EG. Fecal Incontinence: Etiology, Evaluation, and Hayden DM, Weiss EG. Fecal Incontinence: Etiology, Evaluation, and Treatment. Treatment. ClinClin Colon Rectal Colon Rectal SurgSurg 2011;24:642011;24:64--7070

RaoRao SSC. Advances in diagnostic assessment of fecal incontinence and SSC. Advances in diagnostic assessment of fecal incontinence and dyssynergicdyssynergic defecation. defecation. ClinClin GastroenterolGastroenterol HepatolHepatol 2010;8:9102010;8:910--919.e2919.e2

GurlandGurland B, Hull T. B, Hull T. TransrectalTransrectal Ultrasound, Ultrasound, ManometryManometry, and , and PudendalPudendal Nerve Nerve Terminal Latency Studies in the Evaluation of Sphincter Injuries. Terminal Latency Studies in the Evaluation of Sphincter Injuries. ClinClin Colon Colon Rectal Rectal SurgSurg 2008;21:1572008;21:157--166166

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Halland M, Talley NJ. Fecal incontinence: mechanisms and management. Curr Opin Gastroenterol 2012;28:57-62

Lacy BE, Weiser. Common Anorectal Disorders: Diagnosis and Treatment. Curr Gastroenterol Rep 2009;11:413-419

Mellgren A. Fecal Incontinence. Surg Clin N Am 2010;90:185-194

Shah BJ Chokhavatia S Rose S Fecal Incontinence in the Elderly: FAQ Am JShah BJ, Chokhavatia S, Rose S. Fecal Incontinence in the Elderly: FAQ. Am J Gastroenterol 2012;107:1635-1646

Meyer I, Richter HE. Impact of Fecal Incontinence and It’s Treatment on Quality of Life. Women’s Health 2015; 11:225-38

Whitehead WE, Rao SSC, Lowery A, et al. Treatment of Fecal Incontinence: State of the Science Summary for the National Institute of Diabetes and Digestive and Kidney Diseases Workshop. Am J Gastroenterol 2015; 110: 138-46