ABS Complications · 2017. 11. 10. · 2/5/2016 13 ABS Complications Anal Slings-investigational...
Transcript of ABS Complications · 2017. 11. 10. · 2/5/2016 13 ABS Complications Anal Slings-investigational...
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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
Select References
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