Perianal Crohns A Disease For The Physician

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Perianal CrohnsA Disease For The Physician ?

• Alastair CJ Windsor MD FRCS

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• Methods
• Medical records 1970 1995
• Results
• 88 Episodes of fistula in 55 Pts
• Disease Distribution
• 12 (20) Pts first diagnosis
• 19 Ileal
• 59 Ileocolic
• 22 Colonic

Anatomy
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Incidence - VariableInclusion Criteria

• Primary
• Fissure
• Oedematous skin tags
• Cavitating ulcers
• Secondary
• Abscess / fistulae
• Skin tags
• Strictures
• Incidental
• Haemorrhoids
• Tags
• Abscess
• Fistulae

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50
33
26
21
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Traditional Surgical DichotomyConservatives vs
Interventionalists
Interventionalists
Conservatives

• Benign course
• May be asymptomatic
• Spontaneous healing often occurs
• Incontinence is the result of surgery
• Not on maximal medical Rx

• Incontinence
• Chronic diarrhoea
• Non compliant rectal reservoir
• Surgery Favourable outcome
• Sohn - Am J Surg 1980
• 85 healing / 11 proctectomy
• Morrison - Dis Colon Rectum 1989
• 86 healing
• Williams - Dis Colon Rectum 1991
• 93 healing / 15 proctectomy

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Multidisciplinary Care
Stop Press - 2008

• Advent of new biological and immune suppressive
  therapy has changed the approach to managing
  perianal Crohns

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Surgery In The Era Of BiologicalsRemains of
primary importance

• Drain The Sepsis !!
• Sepsis is destructive
• Do not wait for investigation
• Pain and tenderness
• I and D
• Antibiotics
• Mark obvious fistulae
• ECCO European Guidelines

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Assess The Extent Of Disease
E.U.A.
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Assessment Of DiseaseInformation Required

• Colon and Small Bowel
• Extent and severity of proximal disease
• Beware extra sphincteric fistulae
• Rectum
• Extent and severity of disease
• Presence or absence of stricture
• Anal Canal
• Extent and severity of disease
• Number and configuration of fistulae

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Management Of Perianal CrohnsUnifying Approach

• Consider conventional lay open surgery if
• Anatomically Low / simple
• Symptomatic
• No local sepsis
• No rectal involvement
• If not
• Surgical drainage / Seton
• Maximise medical therapy (early azathioprine)
• Consider early Anti TNF Rx
• Adjuvant Surgery
• If this fails, or rectal disease is severe
• Consider diversion
• Discuss proctectomy

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Management Of Perianal CrohnsWhat is maximising
medical therapy ?

• Antibiotics
• Immune suppression
• Biological therapy

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MetronidazoleBernstein et al, Gastroenterology
1980Jakobovitz et al, Am J Gastroenterol 1984

• Bernstein et al
• 21 patients closure in 83 of patients
• 4 subsequent open studies (none controlled)
• Complete closure in 34 - 50 of patients
• Improvement after 6 - 8 weeks of therapy
• Recurs after metronidazole discontinued

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Intravenous Cyclosporin

• 5 patients12 fistulas Mixed
• Complete resolution in 10 of 12 fistulas
• Hanauer and Smith, Am J Gastroenterol 1993
• 16 patients Mixed
• Closure 44, Improved 44
• Present and Lichtiger, Dig Dis Sci 1994
• 9 patients Mixed
• 7 of 9 responded
• Egan, Sandborn and Tremaine. Am J Gastroenterol
  1998

Relapse on switching to oral or stopping
Cyclosporin
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Meta Analysis Azathioprine and 6-mercaptopurine
Maintenance
Active Disease
Pearson, D. C. et. al. Ann Intern Med
1995123132-142
3 Months to efficacy
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Management Of Perianal CrohnsWhat is maximising
medical therapy ?

• Antibiotics
• Immune suppression
• Biological therapy

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InfliximabFistula In Crohns

• Patients
• Infliximab vs Placebo
• End point
• Reduction by 50 number of draining fistulae
• Closure of all fistulae
• Results
• 60 (Inf) vs 26 (Plac)
• 50 (Inf) vs 12 (Plac)
• Criticism

Response of fistulating Crohn's disease to
infliximab treatment assessed by magnetic
resonance imaging
Bell, Halligan, Windsor, Williams, Kamm APT 2003
Present DH. NEJM 1999
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Infliximab for Crohns Fistulas One year
treatment - ACCENT 2 StudySands et al, New
England J Med 2004

• 306 patients
• All received open 5mg doses at weeks 0, 2 and 6
• Response ? 50 reduction draining fistulas
• 195 responders (64) randomised
• 1 year of every 8 weeks 5mg infliximab or placebo

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Infliximab for Crohns Fistulas One Year
Treatment-ACCENT 2 StudyInitial Responders
Healed Completely at 1 Year
P0.009
50
36
40
30
Percent
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20
10
(N96)
(N99)
0
Infliximab Maintenance
Placebo Maintenance
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Infliximab Maintenance TherapyFistulating
Disease - ACCENT 2 StudySurgical Episodes for
Fistula
Placebo (n99)
Infliximab Maintenance 5 mg/kg (n96)
150
126
100
81
65
Mean
57
41
50
7
0
Surgical Episodes
Inpatient Surgical
Outpatient Surgical
Episodes
Episodes
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Long-term Evolution of Disease Behaviour in CD
Cosnes J, et al. Inflamm Bowel Dis.
20028244-250.
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Management Of Perianal CrohnsUnifying Approach

• Consider conventional lay open surgery if
• Anatomically Low / simple
• Symptomatic
• No local sepsis
• No rectal involvement
• If not
• Surgical drainage / Seton
• Consider very early or Top Down anti-TNF
• Adjuvant Surgery
• If this fails, or rectal disease is severe
• Consider diversion
• Discuss proctectomy

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Management Of Perianal CrohnsA Top Down
Approach
Newly Diagnosed Crohn (N 129)
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Step-up versus Top-down Trial
Fistulas
Step-up
Top-down
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10
5
weeks
0
26
52
0
26
52
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Anti-TNF TherapyIssues
Safety
Infection / Sepsis
Malignancy / Lymphoma
Treatment Plan
Once started - Exit Strategy ?
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Current Clinical ApproachSignificant Perianal
Disease

• EUA
• Drain sepsis / insert seton
• ? MRI confirms drainage
• Establish immune suppression
• Early Anti TNF Rx
• Removal of seton at 2 wks
• Adjuvant Surgery

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• 21 Patients Median 3 fistulae
• Management
• Drainage Sepsis
• Insertion of Seton
• Infliximab (0,2,6 weeks)
• Removal seton 2 weeks
• Results 20 Months
• 10 patients Complete response
• 11 patients Partial response
• 0 patients No response

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22 pts Immediate response
Follow Up Median 21 (4 31) mths Four
Sustained healing Five Proctect /
Defunction Four Further Infliximab
No serious adverse events
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Current Clinical ApproachSignificant Perianal
Sepsis

• EUA
• Drain sepsis / insert seton
• (MRI confirms drainage of sepsis)
• Establish immunesuppression
• Early Anti TNF Rx
• Removal of seton at 2 wks
• Adjuvant Surgery

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Crohns Fistula Seton Drainage

• Practice
• Simple
• Few complications
• Principal
• Drainage
• Prevents abscess
• Prevents ongoing destruction
• May be used with
• Anti-TNF /- Thiopurines

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Advancement Flaps For CrohnsRectovaginal
Fistulae
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Advancement Flap

• Schouten WR DCR 2001
• 46 success
• Inversely related to number of attempts
• Nogueras JJ DCR 2002
• 59 success
• Not related to
• Previous surgery, Stoma, Type of fistula
• Incontinence related to previous surgical repair

Would a combined approach with Anti-TNF improve
outcome ?
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Anti-TNF in Rectovaginal FistulaACCENT ll
25 patients with 27 RVF
Infx
Infx
? Combination Surgery with Anti-TNF
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Summary

• Complex problem
• Natural history Destructive
• Management
• Multidisciplinary !!
• Drainage and adequate assessment
• Maximise medical therapy
• Antibiotic / immunesuppression / biologicals
• Adjuvant Surgery
• Surgical Principals
• Drain sepsis
• Superficial disease without rectal involvement
  Surgery
• Complex disease and /or rectal involvement
  Conservative
• Global results of surgery 50 success
• Combination therapy may be the best approach

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If all else fails !!
Six patients whose perianal and ileocolic Crohn's
disease improved in the Dead Sea environment.
Frase GM Niv Y. J Clin Gastroenterol 1995

• 6 Patients
• 4 Fistulas
• 2 improved at two weeks
• 1 healed at two weeks