Perianal Crohns Disease: A Review and Exploration on How t

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Perianal Crohns Disease A Review and
Exploration on How to Improve Outcomes Through
the Use of imaging

• David A Schwartz, MD
• Director, Inflammatory Bowel Disease Center
• Vanderbilt University Medical Center

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Just What are We Talking About?
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Patients with Frequent Episodes of Fecal
Incontinence ( 1 / week)
Schwartz et al. , ACG 2005
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Outline

• Anatomy
• Epidemiology
• Pathogenesis
• Diagnostic Tools
• Surgical Treatment
• Medical Treatment
• Conclusion

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Epidemiology
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Hellers et al, Gut 1980
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Anatomy
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Pathogenesis
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Theory 1 Fistulas begin as ulcers
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Theory 2 Fistulas begin as an anal gland
abscess
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Classification Systems
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Diagnosis
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• Why is a precise evaluation important?
• The key to successful management is to establish
  adequate drainage of all abscesses and to control
  fistula healing. An imaging modality should
  provide a virtual road map for this purpose.

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Does Controlling Fistula Healing Make a
Difference?
N 32
p0.001
p0.014
Requeiro et al, IBD 2003
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Diagnostic Options Used in the Classification of
Perianal Crohns Disease

• History
• Physical Exam
• Imaging
• Fistulography
• CT
• MRI
• Endorectal ultrasound

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A PROSPECTIVE BLINDED COMPARISON OF ENDOSCOPIC
ULTRASOUND (EUS), MAGNETIC RESONANCE IMAGING
(MRI) AND SURGICAL EXAMINATION UNDER ANESTHESIA
(EUA) IN THE EVALUATION OF PERIANAL FISTULAS IN
PATIENTS WITH CROHN S DISEASE (CD)

• David A Schwartz, Maurits J Wiersema, Kika M
  Dudiak, JG Fletcher, Jonathan E Clain, William J
  Tremaine, Alan R Zinsmeister, Ian D Norton, Lisa
  A Boardman, Richard M Devine, John H
  Pemberton,William J Sandborn

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Fistulizing Crohns Disease Patients
MRI
EUS
Surgical Evaluation-EUA
Consensus Gold Standard
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Normal Radial EUS Anatomy
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Study Results

• A prospective triple blinded study compared EUS,
  MRI and EUA in 32 patients with suspect perianal
  Crohns disease.1
• All three methods showed excellent accuracy in
  assessing these patients
• EUS 91 (95 CI 75 - 98)
• EUA 91 (95 CI 75 - 98)
• MRI 87 (95 CI 69 - 96)
• Combining either of the imaging modalities with
  EUA increased the accuracy to 100

1- Schwartz et al., Gastro 2001
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Therapy
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Surgical Treatment
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Perianal Crohns Disease Surgical Treatment
Options

• Fistulotomy
• Setons
• Advancement Flap
• Fibrin Glue
• Diversion / Proctectomy

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Medical Therapy
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MEDICAL THERAPIES
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Agents with Probable Efficacy
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Antibiotics
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Antibiotics

• Metronidazole Typical dose is 250 - 500mg po tid
  /qid, improvement seen after 6-8 weeks.
• All studies are open label.
• Largest study conducted by Bernstein et al 1
• 21 patients studied, healing seen in 83
• Three other studies found healing rate of between
  34 -50 2-5

4-Schneider Deutsche M W 1985 5.Brandt et al
Gastro 1982
1-Bernstein et al. Gastro 1980 2-Schneider et al.
Deutsche Med W 1981 3-Jakobovits et al. American
J Gastro 1984
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Antibiotics (Metronidazole)

• Fistulas re-occur once medicine is stopped
• Adverse events include metallic taste, glossitis,
  nausea and a distal peripheral sensory neuropathy

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Antibiotics (Cipro)

• Typical dose is 500 750 mg po bid, improvement
  seen after 6-8 weeks
• Only study was an open label study of 8 patients
  published in abstract form
• 4 patients had persistent drainage and several
  cases required surgical excision.1

1- Turunen et al. Gastro 1993
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Azathioprine / 6 - MP
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Azathioprine / 6 - MP

• The 5 Controlled trials were summarized in a
  meta-analysis1
• 22 / 41 (54) of patients who received AZA /6-MP
  responded vs. 6 / 29 (21) who received placebo.
• Pooled odds ratio was 4.44 in favor of fistula
  healing

1-Pearson et al. Ann Intern Med. 1995
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1-Korelitz et al. Dig Dis Sci 1985
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Cyclosporine
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Cyclosporine

• 10 studies published using CYA to treat fistulas
  (a total of 64 patients) 1-10
• Overall initial response rate is 83, improvement
  seen by 2 weeks.
• Response is not durable

1-Fukushima, Gastro Jpn 1989 2-Lichtiger, Mt
Sinai J of Med 1990 3-Hanauer, Am J Gastro
1993 4- Present, Dig Dis Sci 1994 5- Markowitz,
Gastro 1990
6-Abreu-Martin, Gastro 1996 7-ONeill, Gastro
1997 8-Hinterleitner, Zeit fur Gastro
1997 9-Egan, Am J Gastro 1998 10-Gurudu J Clin
Gastro 1999
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Agents with Proven Efficacy
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Tacrolimus (FK-506)
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Tacrolimus (FK-506)

• There have been 3 case- studies and 1 controlled
  trial where fistula closure was included in the
  results.1-4
• Similar mechanism of action as Cyclosporine but
  is readily absorbed even from diseased small
  intestinal mucosa

1-Lowry et al. IBD. 1999 2-Sandborn et al. Am J
Gastro. 1997 3-Fellermann et al. Am J Gastro.
1998 4-Sandborn et al. Gastro 2003
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Sandborn et al. , Gastro 2003
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Anti-TNF ? Antibody
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Adalimumab Complete Healing of Draining Fistulas
at Both Wks 26 and 56 Randomized Responders
N70

Schwartz, ACG 2006
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How Can We Improve Outcomes for Patients with
Crohns Perianal Fistulas?
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The Use of Endoscopic Ultrasound (EUS) to Guide
Combination Medical and Surgical Therapy for
Crohns Perianal Fistulas

• DA Schwartz, CM White, PE Wise and AJ Herline
• Inflammatory Bowel Disease Center
• Vanderbilt University Medical Center,
• Nashville, TN

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21 pts with Perianal Crohns Disease
Rectal EUS / Colonoscopy
EUA with ID and Seton Placement
AZA/6-MP, Cipro and Remicade
Serial rectal EUS Exam
Setons were not removed unless EUS proved the
Fistulas were inactive
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Demographics

• 10 (48) had previous perianal surgery
• 5 (24) had received infliximab previously
• The fistulas treated included
• 8 trans-sphincteric
• 2 superficial
• 3 recto-vaginal
• 7 with multiple /or horseshoe fistulas.
• 13 (62) had associated abscesses at
  presentation.

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Utilizing EUS to Improve Fistula Healing
N21
Schwartz et al, IBD 2005
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Results

• Median time to cessation of drainage was 10.6 wks
  (4-32).
• Median time to EUS evidence of fistula inactivity
  was 21 weeks (12-37 weeks).

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Representative Patient Initial EUS
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Representative Patient Week 16
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Representative Patient Week 30
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Prospective randomized study utilizing EUS to
guide combination medical and surgical therapy

• DA Schwartz, PE Wise and AJ Herline
• Inflammatory Bowel Disease Center
• Vanderbilt University Medical Center,
• Nashville, TN

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Methods
10 pts with Perianal CD
Diagnostic colon and EUS, Meds maximized
EUS guided Rx
Conventional Rx
Every 8 weeks pts reassessed clinically
Every 8 weeks pts reassessed clinically
Every 16 weeks EUS - the results used to guide Rx
Week 54- durable fistula healing compared
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Results

• 10 Patients enrolled
• 5 EUS and 5 Control
• 4 of the 5 control patients required recurrent
  surgery
• 2 for recurrent abscess
• 2 for recurrent fistula
• None of the EUS cohort needed repeat surgery.
• All have had cessation of drainage

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Conclusion
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Thank You for Your Time