fecal incontinence novel therapy

Yosef Nasseri M.D.Yosef Nasseri M.D.

Fecal Incontinence – A Novel Therapy

Colorectal SurgeryColorectal Surgery

Agenda

♦ Overview of Fecal Incontinence

♦ Conservative Therapy

♦ Surgical management

♦ Cutting Edge Colorectal Surgery

Overview of Fecal Incontinence

♦ Mechanism of Action

♦ Prevalence and Burden

♦ Patient Quality of Life

♦ Typical Treatment Pathway

Mechanism of Action

VIDEO

Fecal Incontinence-More Common Than You Might Think

● It is estimated that more than 18 million adults in the United States

● 1 in 12 suffer from fecal incontinence (FI)

● FI is nearly as prevalent as many other chronic diseases and more prevalent than other illnesses well-known to impact many Americans

0

5

10

15

20

25

30

35

OAB Asthma Diabetes FI Osteoporosis Alzheimer's

FI Impacts Quality of Life

Fecal Incontinence Quality of Life Scale (FIQOL) ScoresNote: Higher scores translate to higher quality of life

Optimal Medical Therapy

♦ Conservative treatments include:

● Dietary changes

● Fiber supplements

● Anti-diarrheal medications

● Biofeedback

Diagnostic Workup

♦ Endoanal Ultrasound

♦ Anal Manometry

♦ Electromyography (EMG)

Surgical management

♦ Repair ● Sphincteroplasty ● Postanal repair

♦ Augmentation ● Injectables ● Radiofrequency

♦ Replacement ● Dynamic Graciloplasty ● Artificial Bowel Sphincter

♦ Stimulation ● Sacral Nerve Stimulation

Long-term Outcomes of Overlapping Sphincteroplasty:

Meta-analysis

♦ 16 studies

♦ 900 patients

♦ Variable outcome measures

♦ Clear trend toward decay of functional outcomes over time

♦ No predictors for long-term success

Glascow et al. DCR 2012

Long-term Outcomes of Overlapping Sphincteroplasty:

Meta-analysis

Glascow et al. DCR 2012

Augmentation Methods

♦ Injectables

♦ Radiofrequency

Results of Injectables

Author N Material

used

Follow-up

(months)

Wexner Incontinence score

Before After

Shafik et al. 14 Autologous Fat 24 85% improved

Shafik et al. 11 PTFE 24 63% improved

Malouf et al. 10 Bioplastique ® 6 30% improved

Tjandra et al. 82 Silicone 12 50% improved

Tjandra et al. 20 PTQ ® 12 12 4

Sorensen et al. 33 Silicone 12 13 10

Weiss et al. 10 ACYST ® 22 13 10

Results of Injectables

Author NMaterial

used Follow-up (months)

Wexner Incontinence score

Before After

Davis et al. 18 Dursphere® 29 11.8 8

Chan et al. 7 PTQ ® 14 9-14 1-5

Stojkovic et al. 73 Contigen ® 12 10 6

De la Portilla et al. 20 PTQ ® 24 13.5 9.4

Maeda et al. 10Bulkamid ®

1915 12

Permacol ® 16 15

Schwander et al. 21 Hyarulonic 20 17 12

Graf et al. 206 Solesta ® 12 10 5

Radiofrequency (SECCATM)

Radiofrequency (SECCATM)

Results of Radiofrequency

Author (year) nF/U

(months)

Wexner Score

QOLBefore After

Takahashi 2002 10 12 13.5 5 ↑

Efron 2003 50 6 14.5 11 ↑

Takahashi 2003 10 24 13.8 7 ↑

Felt-Bersma 2007 11 12 18.8* 15* ↑

Takahashi 2008 19 60 14.4 8 ↑

Lefebure 2008 15 12 14.7 12.3 ↑**

Kim 2009 8 6 13.6 9.9 -

Walega 2009 20 6 Improved ↑

Ruiz 2010 16 12 15.6 12 ↑

Herman 2011 40 12 16 10.9 ↑

Abbas 2012 27 36 Only 22% improved --

* Vaizey score ** only depression improved

Artificial Bowel Sphincter (ABS)

Cuff

Balloon

Pump

FDA approved in 1999

Outcomes of Artificial Bowel Sphincter

Author n F/U (months)

Infection (%)

Explant/Reimplant Functional(%)

Wong 1996 12 58 25 7/4 75

Lehur 1998 13 30 8 4/2 85

Vaizey 1998 6 10 33 1/0 83

Christiansen 1999 17 60 18 7/0 53

Lehur 2000 24 20 4 8/4 83

Dodi 2000 8 10.5 25 2/0 75

O’Brien 2000 13 - 23 3/0 77

Altomare 2001 28 19 18 5/0 75

Lehur 2002 16 25 0 6/1 75

Devesa 2002 53 26.5 21 12/2 49

Ortiz 2002 22 28 9 9/2 68

Wong 2002 112 12 38 41/7 67

Michot 2003 25 34.1 12 5/0 76

Parker 2003 37 12 19 27/7 49

Casal 2004 10 29 10 3/2 90

Ruiz-Carmona 2008 17 68 29 11/3 53

Wexner 2009 47 39 41 18/4 65

Factors associated with ABS failure

♦ 51 ABS in 47 patients

♦ Mean age: 48.8 years

♦ Mean Wexner score: 18 (0-20)

♦ Etiology of incontinence:

● Imperforate anus: 24 (54%)

● Obstetric injury / anorectal surgery: 15 (24%)

● Other: 12 (22%)

Wexner et al. DCR. 2009

Factors associated with ABS failure

♦ Infection 23 (41%)

♦ Non significant factors on univariate analysis:● Age● Gender● BMI● Diabetes Mellitus● Etiology● Stoma● Perianal infection / surgery

Early 18

(35%)

Late 5

(6%)

Wexner et al. DCR. 2009

Factors associated with ABS failure

♦ Multivariate analysis:

♦ Time between ABS implantation to 1st bowel

movement

♦ History of perianal sepsis

♦ Late failures

● More often due to device malfunction

● Indicated the need for mechanical refinement

Wexner et al. DCR. 2009

Sacral Neuromodulation

Sacral Neuromodulation

An established therapy that expands your treatment options for patients with chronic fecal incontinence who have failed or are not candidates for more conservative treatments.

Sacral NeuromodulationMechanism of action

VIDEO

Sacral NeuromodulationMechanism of action

♦ Focuses mild electrical pulses on the nerves that control the pelvic floor muscles, anal sphincters, and colon

♦ Either an excitation of parasympathetic nerves or a release from the inhibition of the sympathetic nerves (or both) may be hypothesized

Author n F/U (months) Scoring Method Before After p

Malouf (2000) 5 16 Wexner 16 2 <0.01

Ganio (2001) 16 15.5 Williams 4.1 1.25 0.01

Leroi (2001) 6 6 FI episodes/ 1wk 3.2 0.05 < 0.05

Matzel (2001) 6 5-66 Wexner 17 2 NR

Rosen (2001) 16 15 FI episodes/3 wks 6 2 NR

Kinefick (2002) 15 24 FI episodes/1 wk 11 0 <0.001

Jarrett (2004) 46 12 FI episodes/1 wk 7.5 1 <0.001

Matzel (2004) 34 24 FI episodes/1 wk 16.4 2.0 <0.0001

Rasmussen (2004) 45 6 Wexner 16 6 <0.0001

Uludag (2004) 75 12 FI episodes/1 wk 7.5 0.67 <0.01

Holzer (2007) 29 35 FI episodes/3 wks 7 2 0.002

Hetzer (2007) 37 13 Wexner 16 5 <0.01

Sacral Nerve Stimulation Results

Author n F/U (months) Scoring Method Before After p

Melenhorst (2007) 100 36 FI episodes/1 wk 31.3 4.8 <0.0001

Matzel (2008) 9 117.6 Wexner 17 10 <0.007

Tjandra (2008) 53 12 Wexner 16 1.2 <0.0001

Altomare (2009) 52 60 Wexner 15 5 < 0.001

Boyle (2009) 13 3-6 Wexner 12 9 0.0005

Dudding (2010) 9 46 FI episodes/1 wk 9.9 1.0 0.031

Michelsen (2010) 177 24 Wexner 16 10 <0.0001

Vallet (2010) 23 44 Wexner 16 6.9 NR

Wexner (2010) 120 28 FI episodes/1 wk 9.4 2.7 <0.0001

Lim (2011) 41 51 Wexner 11.5 8.0 <0.001

George (2012) 25 114 FI episodes/wk 22 0 0.001

Hull (2012) 120 60 FI episodes/wk 9.4 1.7 <0.001

Sacral Nerve Stimulation Results

Sacral nerve Stimulation Meta-Analysis

♦ 34 studies – 665 patients

♦ Significant improvements in Number of incontinent episodes Wexner Fecal Incontinence Score Ability to defer evacuation Most SF-36 and FIQL domains Mean anal resting pressures

15% Morbidity – 3% Explantation

Sacral Nerve Stimulation Sacral Nerve Stimulation Quality of LifeQuality of Life

SF-36 FIQOLCategories Improved

Lifestyle Coping/

Behavior

Depression/ Self-

perception

Embarrassment

Malouf Most – – – –

Rosen – Kenefick Most – – – –

Ripetti Most – – – –

Matzel – Altomare – Matzel Most

Matzel et al. DCR 2004

Demographics 120 Implanted Subjects

♦ Age: 60.5 years (30 - 88)

♦ Gender: 92% female, 8% male

♦ Years with fecal incontinence: 6.8 (1 - 44)

Wexner et al. Ann Surg. 2010

Primary Efficacy Objective: Weekly Incontinent Episodes

Wexner et al. Ann Surg. 2010

73%

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

12-Month (n=120)

Primary Objective

Clin

ical S

uccess R

ate

(%

Su

bje

cts

)

64%

81%

Performance Criterion

Clinical Success: ≥ 50% Reduction in Weekly Incontinent Episodes from Baseline to 12 Months

(p < .0001)

Primary Efficacy Objective: Weekly Incontinent Episodes

Wexner et al. Ann Surg. 2010

Absolute Reduction - Sensitivity Analysis

0.00

1.00

2.00

3.00

4.00

5.00

6.00

7.00

8.00

9.00

10.00

Me

an

We

ek

ly In

co

nti

ne

nt

Ep

iso

de

s

Modified Worst Case Analysis(n=120)

9.39 3.08

LOCF Analysis (n=120) 9.39 2.54

Completers Analysis (n=106) 9.19 1.92

Baseline 12-Month

Secondary Efficacy Objective: Weekly Urgent Incontinent Episodes

Wexner et al. Ann Surg. 2010

% Reduction - Sensitivity Analysis

0.00

1.00

2.00

3.00

4.00

5.00

6.00

Me

an

We

ek

ly U

rge

nt

Inc

on

tin

en

t E

pis

od

es

Worst Case Analysis(n=120)

4.95 1.73

LOCF Analysis (n=120) 4.95 1.36

Completers Analysis (n=106) 4.91 1.15

Baseline 12-Month

Secondary Efficacy Objective: Fecal Incontinence Quality of Life

Wexner et al. Ann Surg. 2010

Mean FIQOL - Multiple Follow-ups

1

1.5

2

2.5

3

3.5

4

Mea

n F

IQO

L S

core

(Co

mp

lete

rs A

nal

ysis

)

Scale 1 - Lifestyle 2.31 3.22 3.26 3.36 3.26 3.41

Scale 2 - Coping/Behavior 1.49 2.64 2.69 2.77 2.67 2.52

Scale 3 - Depression/Self-Perception 2.53 3.33 3.48 3.55 3.61 3.65

Scale 4 - Embarrassment 1.6 2.73 2.75 2.81 2.76 2.65

Baseline (n=119)

3-Month (n=116)

6-Month (n=109)

12-Month (n=107)

24-Month (n=43)

36-Month (n=18)

Additional Study MeasuresSelf-rated Bowel Health

Wexner et al. Ann Surg. 2010

Mean Plot of Changes in Self-rated Bowel Health

7.28

3.53

0.00

1.00

2.00

3.00

4.00

5.00

6.00

7.00

8.00

9.00

10.00

Baseline 12-Months

Mean Change from Baseline to 12 Months (n=106)

Sel

f-ra

ted

Bo

wel

Hea

lth

(p < .0001)

Morbidity Most Frequent Device/Therapy-Related

Adverse Events

Wexner et al. Ann Surg. 2010

♦ Test Stimulation Phase (n=132)

● Implant site pain (3.8%)

● Lead fracture (1.5%)

♦ Implant Phase (n=120)

● Implant site pain (25.8%)

● Implant site infection (10.8%)

● Paraesthesia (10.8%)

● Change in sensation of stimulation (5.8%)

● Diarrhea (5.8%)

● Pain (5%)

● Urinary incontinence (5.0%)

Morbidity Infectious complications

♦ 13 women

♦ Mean age of 54.5 years (33-85)

♦ Mean BMI of 26.4 kg/m2 (19.3-39)

♦ One patient with non-insulin dependant diabetes

♦ Two patients had lower back surgery

♦ No steroid use

Wexner et al. Ann Surg. 2010

Patients with infectious complication (n=13)

Morbidity Infectious complications

Risk Factor No. of patients

Age > 65 4

BMI > 30 3

BMI > 35 2

NIDDM 1

Lower back surgery 2

Steroid use 0

Patients with infectious complication (n=13)

Wexner et al. J Gastrointest Surg 2010

Morbidity Infectious complications

Implant Phase (n=120)

Early events

6 infections were reported at a mean of 11 (range 7-18) days post implant and successfully treated with oral antibiotics

Wexner et al. Ann Surg. 2010

Morbidity Infectious complications

Implant Phase (n=120)

Late events

7 infections were reported at a mean of 7 (range 2-14) months after implant. 6 were totally or partially explanted, 1 successfully re-implanted

Wexner et al. Ann Surg. 2010

SNS Long-term efficacy & Safety120-Patient Prospective Multi-center Study

♦ Mean Follow-up: 36 (2-73) months♦ Therapeutic Success (50% improvement)

● 12 months → 83%● 24 months → 86%● 36 months → 85%

♦ Perfect continence● 12 months → 41%● 24 months → 38%● 36 months → 37%

Wexner et al. Ann Surg. 2010

SNS Long-term efficacy & Safety120-Patient Prospective Multi-center Study

Mellgren et al. DCR 2011

SNS Long-term efficacy & Safety120-Patient Prospective Multi-center Study

Mellgren et al. DCR 2011

SNS Long-term efficacy & Safety120-Patient Prospective Multi-center Study

Mellgren et al. DCR 2011

Significant improvement (p< 0.0001) in all 4 scales of the FIQOL from baseline to 3 years

SNS Long-term efficacy & Safety120-Patient Prospective Multi-center Study

Mellgren et al. DCR 2011

♦ Common adverse events:● Pain: 28%

● Infection: 11%

● Paraesthesia: 14%

SNS for Fecal Incontinence: Long-term durability

Prospective Multi-center Study

Hull et al. DCR 2012

♦ Mean Follow-up: 60.4 (2.2 – 99.2) months♦ 74 patients available at 5 year follow-up♦ FI episodes (p<.001):

● 9.4 episodes/week at baseline● 1.7 episodes/week at 5 yrs

♦ 88% had success (≥ 50% improvement) (p<.001)♦ 36% had complete continence♦ FIQOL scores also significantly improved for all 4 ♦ scales between baseline and 5 yrs (p<.001)

SNS Six Year Follow-UpThe Danish Experience

Michelsen et al. DCR 2010

♦ 2001 - 2007♦ 177 patients underwent PNE test♦ Reasons FI (SNS implanted):

● 46.0% idiopathic● 25.4% traumatic or obstetric● 11.1% anorectal surgery● 17.5% others

♦ 126 had SNS implanted

SNS Six Year Follow-UpThe Danish Experience

Michelsen et al. DCR 2010

♦ Permanent lead in S3: 105 patients♦ Permanent lead in S4: 21 patients♦ Explantation: 15 out of 126 (12%)

● Decrease function: 11● Infection: 2● Technical failure: 1

♦ Explantation: Median time 357 (24-1238) days

SNS Six Year Follow-UpThe Danish Experience

Michelsen et al. DCR 2010

Median Wexner incontinence score through the follow-up period

p< 0.001 for 3 and 6 months, and 1, 2, 3, 4 and 6 years. p<0.001 for 5 years

SNS Long-term results10 years Follow-up

Matzel et al. Colorectal Dis 2009

♦ 1994 - 1999♦ 9 patients♦ Mean follow-up 9.8 (7-14) years♦ Median number of incontinent episodes/week: 9 to 0♦ Median Wexner score: 17 to 10♦ Quality of life improved in all categories♦ Pulse generator exchange was required in 8/9 at mean of 7.4 yrs♦ Complications: 4/12 (33%)

● Pain (2)● Displacement (1)● Urinary retention (1)

SNS and Sphincter DefectSystematic Review

Ratto et al. Colorectal Dis 2012

♦ 10 studies (119 patients) met inclusion criteria● 9 retrospective● 1 prospective

♦ Definitive implant in 106 patients (89%)

♦ Follow-up: 22.9 (4.5-46) months

SNS and Sphincter DefectSystematic Review

Ratto et al. Colorectal Dis 2012

Significant findings:

♦ Wexner Fecal Incontinence Score: 16.5 to 3.8

♦ Incontinent episodes per week: 12.1 to 2.3

♦ Ability to defer defecation

♦ Fecal Incontinence Quality of life Scale

♦ No change in anorectal manometry

SNS for fecal incontinence associated with other specific conditions

IndicationAuthor/

YearPatients

(n)

Improved Outcomes(Wexner FI, Number

incontinent episodes, QOL)

Rectal Resection Holtzer 2008 7 71%

Rectal Resection De Miguel 2010 7 100%

Rectal prolapse surgery RobertYap 2010 11 100%

Pelvic floor injury Oom 2010 29 86%

Radiation Maeda 2010 7 83%

Spinal cord injury Lombardi 2010 37 59%

SNS - Technique

VIDEOS

What’s Next for Patients?

Consider InterStim Therapy to those patients who aren’t responding favorably to medical therapy.

Overview of Trial Assessment

● Through a minimally invasive procedure initiated in the office or in an outpatient hospital setting, a lead (thin wire) is placed near the sacral nerve (target S3)

● The lead is connected to an external test stimulator worn on the patient’s waistband for several days.

● The patient will be asked to record bowel behavior during the trial

● If patient experiences success, a neurostimulator may be implanted

● If patient does not experience success, a subsequent trial assessment may be recommended

● If patient still does not experience success, the lead will be removed and the patient will immediately be able to try other options

ImplanterReferring Physician ImplanterReferring PhysicianReferring Physician

CollaborativeProcess toOptimize

Patient Care

Initial Diagnosis

Initial Diagnosis

Conservative Treatments

Conservative Treatments

ReferralReferral

InterStimImplant

InterStimImplant

Device-related Follow-up

Ongoing General Patient Care

Ongoing General Patient Care

InterStimTrial Assessment

InterStimTrial Assessment

Benefits of Referring Your Patients

● Practical and extensive experience with InterStim Therapy

● Offering your patients a minimally invasive option that can restore function1

● We will collaborate to develop a follow-up plan once symptoms are successfully treated

What Should You Tell Your Patients?

♦ “I would like to refer you to a specialist who will evaluate your condition further and determine if InterStim Therapy might be an option for you”

♦ “The InterStim trial assessment will give you a chance to find out during a short trial period if long-term therapy may be a good option for you”

♦ “InterStim Therapy is an established therapy that is FDA approved for chronic fecal incontinence patients who have not benefited from conventional therapies”

Summary ♦ Fecal incontinence (FI) is very common and may impact a person’s quality of life

♦ Patients may be embarrassed to discuss FI symptoms and are often unaware of the new treatment options available

♦ If conservative treatments have been unsuccessful, refer patients to my practice to determine if InterStim Therapy is an option for them

♦ By partnering, you can expand patients’ treatment options and help find the best solution to manage their symptoms

♦ Together we can improve the quality of life for patients with bowel control problems

Cutting Edge Colorectal Surgery

♦ TEM (Transanal Endoscopic Microsurgery)

♦ Total Laparoscopic Surgery

♦ Robotic Surgery

♦ Gracilis flap for recto-vaginal/recto-urethral fistulas

TEM (Transanal Endoscopic Microsurgery)

Rectal Cancer: Treatment Options

TEM Local Excision

Removal some node bearing tissue

Disc excision of the

rectal wall

Lower recurrence rates (2-

10%)

Higher recurrence rates (up to 25%)

Better staging ? Staging

TEMJust another local excision?

• What’s so special?

Optimal visualization

3D Image

Balanced insufflation

Access to mid and upper rectum

Potential for lymphadenectomy

Total Laparoscopic Surgery

Total Laparoscopic Surgery

♦ Decrease in wound size

♦ Reduction in wound infection, dehiscence, bleeding, herniation and nerve entrapment

♦ Decrease in wound pain

♦ Improved mobility

Robotic Surgery

How Has Colorectal Surgery Evolved?

da Vinci®

Surgery

How Does My Robotic Surgery Room Look?

da Vinci Low Anterior Resection - Rectal Cancer

Gracilis flap for recto-vaginal/recto-urethral fistulas

1. Patient’s position 2. Distal medial thigh incision

3. Two thigh incisions 4. Muscle mobilization5. Neuro-vascular pedicle identification

Gracilis flap for recto-vaginal/recto-urethral fistulas

Gracilis flap for recto-vaginal/recto-urethral fistulas

♦ A viable option for repairing RVF and RUF,

especially after failed perineal or transanal repair

♦ It is associated with low morbidity and good success

rate