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Diagnosis and Management of Crohn’s Disease of
th Il l P h
Diagnosis and Management of Crohn’s Disease of
th Il l P hthe Ileal Pouchthe Ileal Pouch
Bo Shen, MDCleveland Clinic
December 5, 2008
Bo Shen, MDCleveland Clinic
December 5, 2008
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Indications for ColectomyIndications for Colectomy
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Ileal Pouch-anal Anastomosis (IPAA)
Ileal Pouch-anal Anastomosis (IPAA)
Colectomy
CCF© 2000
J pouch
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Owl’s Eyes
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Ileal Pouch Disorders and Associated ComplicationsIleal Pouch Disorders and Associated Complications
FunctionalSurgical/Mechanical
Inflammatory/Infectious
Dysplastic/Neoplastic
Systemic/MetabolicMechanical Infectious
- Anastomotic leaks- Pelvic sepsis- Pouch sinuses- Pouch fistulae
- Anastomotic leaks- Pelvic sepsis- Pouch sinuses- Pouch fistulae
- Pouchitis- Cuffitis- Crohn’s dis.- Small
- Pouchitis- Cuffitis- Crohn’s dis.- Small
- Irritablepouch syn.
- Anismus- Poor
- Irritablepouch syn.
- Anismus- Poor
Neoplastic
- Pouchdysplasiaor cancer
- ATZ
- Pouchdysplasiaor cancer
- ATZ
Metabolic
- Anemia- Bone loss- Vitamin B12deficiency
- Anemia- Bone loss- Vitamin B12deficiencyPouch fistulae
- Strictures- Afferent limb syn.- Efferent limb syn.- Infecundity- Sexualdysfunction
Pouch fistulae- Strictures- Afferent limb syn.- Efferent limb syn.- Infecundity- Sexualdysfunction
Smallbowel bacterialovergrowth
-InflammatoryPolyps
Smallbowel bacterialovergrowth
-InflammatoryPolyps
pouch compliance
- Pseudo-obstruction
- Hypersensitivesuture line
pouch compliance
- Pseudo-obstruction
- Hypersensitivesuture line
dysplasiaor cancer
- Lymphoma- Squamous cell cancer
dysplasiaor cancer
- Lymphoma- Squamous cell cancer
y- Portal vein thrombi- Pouch prolapse- Foreign bodies
y- Portal vein thrombi- Pouch prolapse- Foreign bodies
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100
Crohn’s Disease in Patients with IPAACrohn’s Disease in Patients with IPAA
40
60
80
e Fr
eque
ncy
%e
Freq
uenc
y %
2.7 3.5 4.1 4.8 7 913
0
20
40
Yu Duetsch Fazio Neilly Gemlo Keighley Peyregne
Cum
ulat
ive
Cum
ulat
ive
2000 1991 2003 1999 1992 2000 1999
N = 1519N = 1519 N = 1816N = 1816N = 272N = 272 N = 171N = 171 N = 196N = 196 N = 54N = 54N = 222N = 222
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Risk Factors for Crohn’s Disease of the Pouch
Younger ageYounger ageFemaleSmokerFamily history of Crohn’s diseasePreoperative diagnosis of indeterminate
FemaleSmokerFamily history of Crohn’s diseasePreoperative diagnosis of indeterminatePreoperative diagnosis of indeterminate colitisSero-positive anti-Saccharomyces cerevisiae-IgA
(different risk factors for clinical phenotypes)
Preoperative diagnosis of indeterminate colitisSero-positive anti-Saccharomyces cerevisiae-IgA
(different risk factors for clinical phenotypes)(different risk factors for clinical phenotypes)(different risk factors for clinical phenotypes)Melmed GY, et al. DCR 2008Delaney CP, et al. Ann Surg 2002Shen B, et al. AJG 2006Shen B, et al, CGH 2006Shen B, et al. IBDJ 2008
Melmed GY, et al. DCR 2008Delaney CP, et al. Ann Surg 2002Shen B, et al. AJG 2006Shen B, et al, CGH 2006Shen B, et al. IBDJ 2008
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Phenotypic ClassificationInflammatoryInflammatory FibrostenoticFibrostenotic FistulizingFistulizing
Shen B, CGH 2008
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DiagnosisDiagnosis
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Terminology
Crohn’s diseaseCrohn’s disease of the pouch √Crohn’s-like Or a totally “unknown” disease entity
Crohn’s diseaseCrohn’s disease of the pouch √Crohn’s-like Or a totally “unknown” disease entityOr a totally unknown disease entityOr a totally unknown disease entity
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“Hallmarks” of Crohn’s DiseaseGranulomasSkip lesionsTransmural inflammationFistula
GranulomasSkip lesionsTransmural inflammationFistula
pseudogranulomasischemiachronic pouchitisSurgery-related
pseudogranulomasischemiachronic pouchitisSurgery-relatedFistulaFistula Surgery relatedSurgery related
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100
Granulomas in Crohn’s Disease of IPAA
60
80
ive
Freq
uenc
y %
12 12 10
0
20
40
Cum
ulat
0Inflammatory Fibrostenotic Fistulizing
N = 25 N = 31N = 17
Shen B, et al AJG 2006Shen B, et al AJG 2006
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Foreign-body GranulomasForeign-body Granulomas
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Pyloric Glands and Pyloric Gland Metaplasia
N = 110Sensitivity = 63.8% ; Specificity = 96.2%Likelihood ratio = 16.7 Pouch failure: 12.8% in PGM+ vs. 1.4% in PGM- (P = 0.02)
Kariv R. et al DDW 2007
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Causes of Afferent Limb Inflammation (Ileitis)( e t s)
NSAID inducedBackwash ileitis from diffuse pouchitisSurgery-related ischemia or ischemic ileitis
NSAID inducedBackwash ileitis from diffuse pouchitisSurgery-related ischemia or ischemic ileitisg yCrohn’s ileitis
g yCrohn’s ileitis
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Differential Diagnosis of Distal IleitisBackwashIleitis from diff
BackwashIleitis from diffdiffuse pouchitisdiffuse pouchitis
NSAID inducedNSAID induced
CDCD
Afferent LimbAfferent Limb Pouch InletPouch Inlet Pouch BodyPouch Body
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Segmental Pouchitis-Pattern of Ischemic Injury
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Extracellular Pigments in Ischemic Pouchitis
Shen B, et al. DDW 2009Shen B, et al. DDW 2009
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Antibiotic-
Features of Ischemic Pouchitis
Ischemic Pouchitis(N = 10)
CD Pouch( N= 15)
responsive Pouchitis(N = 15) P value
Symptom score 3 (0, 5) 3 (2, 4) 4 (2, 4) 0.66Pouch endoscopy score 2.5 (2, 4) 1 (0, 3) 4 (3, 5) 0.014
A-limb endoscopy score 0 (0, 0) 2 (0, 3) 0 (0, 0) 0.001Cuff endoscopy score 0 (0, 2) 0.5 (0, 3) 0 (0, 2) 0.78Any response to antibiotics 2 (20.0%) 13 (86.7%) 15 (100%) 0.001Granulomas 0 2 (15.4%) 0 0.17Pyloric gland metaplasia 0 3 (23.1%) 2 (13.3%) 0.34Histologic ulcers 4 (40.0%) 2 (15.4%) 3 (20.0%) 0.4Extracellular pigment 8 (80.0%) 4 (30.8%) 2 (13.3%) 0.003
Shen B, et al. DDW 2009Shen B, et al. DDW 2009
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Ischemia CD Pouch
Distinction between Ischemic and Crohn’s Stricture
Ischemia CD Pouch
Location of strictures Ileostomy site, inlet/outlet Anywhere
Fistula - +Granulomas - +Granulomas +Pyloric gland metaplasia - +Extracellular pigment + +/-Response to medicines - +/-R t d i t + +/Response to endoscopic tx + +/-
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Optical Coherence Tomography for Transmural Inflammation
Normal PouchNormal Pouch
Acute PouchitisAcute Pouchitis
Shen B. DDW 2009
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Optical Coherence Tomography for Transmural Inflammation
Chronic PouchitisChronic Pouchitis
Crohn’s PouchCrohn’s PouchPouchPouch
Shen B. DDW 2009
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Transmural Inflammation-A Sign of Crohn’s?Transmural Inflammation-A Sign of Crohn’s?
Chronic PouchitisChronic Pouchitis Crohn’s Disease of PouchCrohn’s Disease of PouchShen B. DDW 2009
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Histopathology of Pouch Resection Specimens
Histopathology of Pouch Resection Specimens
Crohn’s(N =16)
Chronic Pouchitis
(N = 10)P value
Granulomas 19% 0 0.14
P l i l d t l i 50% 50% 1 0Pyloric gland metaplasia 50% 50% 1.0
Intraepithelial lymphocytosis
0 0 NA
Transmural inflammation 13% 35% 0.27
Dysplasia 0 10% NA
Fistula 38% 0 0.049
Shen B. DDW 2009
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Fecal and Serum ASCA in Distinction of CDfrom Other Pouch Conditions ROC Curve
Fecal ASCA
Serum ASCA
Tang L, et al. CCFA Miami 2008Tang L, et al. CCFA Miami 2008
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Causes of Fistula/Sinus
Surgical leaksCryptoglandular abscessIatrogenicCrohn’s disease
Surgical leaksCryptoglandular abscessIatrogenicCrohn’s diseaseCrohn s diseaseCrohn s disease
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Pouch Vaginal Fistula
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Not All Pouch-vaginal Fistulae Are From Crohn’s
Courtesy of Dr. Victor FazioCourtesy of Dr. Victor Fazio
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Identification of Internal Os of Fistula
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Perianal Fistula / Pouch-vaginal Fistula A Sign of Crohn’s Disease?
Location and Timing Are the Key
Above the anastomosisAbove the anastomosis
At the anastomosisAt the anastomosis
J pouchJ pouchBelow the anastomosisBelow the anastomosis
Cut-off: 6 – 12 months after ileostomy take-downCut-off: 6 – 12 months after ileostomy take-down
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Pouch Endoscopy & BiopsyPouch Endoscopy & Biopsy
Diagnostic Algorithm
Crohn’s Disease
Suspected
Pouchitis/Ileitis
Iatrogenic Complications, fistula, leaks)
Crohn’s Disease
Confirmed
Cuffitis5-ASA Failure5-ASA Failure
Antibiotic FailureAntibiotic Failure
Contrasted EnemaCTE/MRE
MRI Pelvis, EGD
Contrasted EnemaCTE/MRE
MRI Pelvis, EGD
Diagnostic/Therapeutic EUA
Diagnostic/Therapeutic EUATherapeutic EUATherapeutic EUA
Trial of BiologicsTrial of
BiologicsShen B. IBDJ 2008Shen B. IBDJ 2008
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TreatmentTreatment
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Crohn’s Disease Pouch
Management Algorithm for Crohn’s Pouch
Inflammatory Fibrostenotic Fistulizing
Medical Therapyibi i ?
Medical Therapyibi i ?
Medical TherapyA ibi i ?
Medical TherapyA ibi i ?
Medical TherapyMedical TherapyAntibiotics?
5-ASAs,Corticosteroids,
Immunomodulators,Biologics
Antibiotics?5-ASAs,
Corticosteroids,Immunomodulators,
Biologics
Antibiotics?5-ASAs, Corticosteroids,
Immunomodulators,Biologics?
Endoscopic Therapy
Antibiotics?5-ASAs, Corticosteroids,
Immunomodulators,Biologics?
Endoscopic Therapy
pyAntibiotics,
Immunomodulators,Biologics
Endoscopic Therapy?
pyAntibiotics,
Immunomodulators,Biologics
Endoscopic Therapy?
SurgeryIncision & Drainage, Seton, Stricturoplasty, Fistular
Repair, K Pouch, Diversion, Pouch Excision
SurgeryIncision & Drainage, Seton, Stricturoplasty, Fistular
Repair, K Pouch, Diversion, Pouch ExcisionShen B,IBDJ 2008
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Infliximab for CD of the PouchInfliximab for CD of the Pouch100 - N = 26 (ileitis=5; ileitis-fistula=7; fistula =14)
C t i d t 15
62%
40
60
80
% o
f Ca
ses
- Concurrent immunomodator = 15- Median f/u = 22 months
Fistular closure= 50% (9/18)
33%
15%23%
0
20
40
C l t P ti l N P h
%
Colombel JF, et al. AJG 2003
CompleteResponse
PartialResponse
NoResponse
PouchFailure
Induction Therapy
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Adalimumab for Crohn’s Disease of PouchFactor AllSymptom Improvement
Partial 6 (35.3)Complete 7 (41.2)
Endoscopic Inflammation ImprovementPartial 4 (28.6)Complete 7 (50 0)Complete 7 (50.0)
Fistular Response (N=5)Partial 1 (20.0)Complete 1 (20.0)
Adverse EffectHeadache 3 (17.7)Injection Site Reaction 1 (5.9)
Pouch Failure 3 (17.7)
N = 17; 4 wk induction therapyN = 17; 4 wk induction therapy Shen B, et al APT 2009Shen B, et al APT 2009
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Stricture Dilations
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Needle Knife “Stricturoplasy”
Shen B. IBDJ 2008
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Needle Knife “Fistulotomy”
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Pouch-cutaneous Fistula: EndoClip
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Natural History and PrognosisNatural History and Prognosis
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Clinical Setting of Crohn’s Disease of Pouch
Intentional CD pouch: in a selected group of patients with a preop diagnosis of Crohn’s colitis Incidental CD pouch: in patients with a missed diagnosis of Crohn’s diseasegDe novo CD pouch
(Diagnosis of pouch conditions can change over time)
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Early vs. Late-onset of Crohn’s Disease of the Pouch
Early vs. Late-onset of Crohn’s Disease of the Pouch
Occ
urre
nce
Occ
urre
nce
Months-Years
OO
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100100
Pouch Failure in Patients with Crohn’s DiseasePouch Failure in Patients with Crohn’s Disease
45.9 46.2 47.846.242.9 44.4
40
60
80
ativ
e Fr
eque
ncy
%at
ive
Freq
uenc
y %
25.4
0
20
40
Fazio Peyregne Duetsch Sagar Gemlo Tulchinsky Keighley Neilly
Cum
ula
Cum
ula
1995y g1999 1991
g1996 1992
y2003
g y2000
y1999
N = 67N = 67 N = 19N = 19N = 79N = 79 N = 37N = 37 N = 13N = 13 N = 23N = 23N = 13N = 13 N = 8N = 8
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Phenotypes of Crohn’s Disease and Pouch Survival
Shen B, et al. IBDJ 2008Shen B, et al. IBDJ 2008
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Pouch Survival in Different SettingsUC or Indeterminate colitis
N = 2 630
Incidental CD N=97
N = 2,630
53%
87%
De novo CD N=87
Melton GB, et al. Ann Surg 2008
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7 months
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Crohn’s Disease and Cancer Risk
Prevalence: 10/2700 with IPAA underlying UCPoorly-differentiated cancer: 4Concurrent Crohn’s disease: 6Precolectomy dysplasia: 7
Prevalence: 10/2700 with IPAA underlying UCPoorly-differentiated cancer: 4Concurrent Crohn’s disease: 6Precolectomy dysplasia: 7Mucosectomy not necessarily protective: 3“Missed dysplasia” in routine surveillance: 3/71-year mortality: 40%
Mucosectomy not necessarily protective: 3“Missed dysplasia” in routine surveillance: 3/71-year mortality: 40%
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ConclusionsCD of the pouch can occur in patients with a preoperative diagnosis of UC or ICCD of the pouch can occur in patients with a preoperative diagnosis of UC or ICpreoperative diagnosis of UC or IC.Natural history varies.Diagnosis and differential diagnosis can be challenging, and a combined assessment of clinical endoscopic imaging and histologic
preoperative diagnosis of UC or IC.Natural history varies.Diagnosis and differential diagnosis can be challenging, and a combined assessment of clinical endoscopic imaging and histologicclinical, endoscopic, imaging, and histologic features is often needed.Phenotypic classification may be useful for “targeted” therapy and prognosis.
clinical, endoscopic, imaging, and histologic features is often needed.Phenotypic classification may be useful for “targeted” therapy and prognosis.
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Anatomy of Pelvic PouchAnatomy of Pelvic Pouch“J”“J” “S” “W”Afferent limb
(neo-terminal il )
Afferent limb (neo-terminal il )
Tip of “J”Tip of “J”
ileum)ileum)InletInlet
Efferent limb Efferent limb
Outlet/cuffOutlet/cuffOutlet/cuffOutlet/cuffEfferent
limb Efferent
limb
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Sinus vs. Crohn’s Fistula
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Carolyn Roach, PVF Setons