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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

Indications for ColectomyIndications for Colectomy

Ileal Pouch-anal Anastomosis (IPAA)

Ileal Pouch-anal Anastomosis (IPAA)

Colectomy

CCF© 2000

J pouch

Owl’s Eyes

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

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

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

Phenotypic ClassificationInflammatoryInflammatory FibrostenoticFibrostenotic FistulizingFistulizing

Shen B, CGH 2008

DiagnosisDiagnosis

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

“Hallmarks” of Crohn’s DiseaseGranulomasSkip lesionsTransmural inflammationFistula

GranulomasSkip lesionsTransmural inflammationFistula

pseudogranulomasischemiachronic pouchitisSurgery-related

pseudogranulomasischemiachronic pouchitisSurgery-relatedFistulaFistula Surgery relatedSurgery related

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

Foreign-body GranulomasForeign-body Granulomas

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

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

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

Segmental Pouchitis-Pattern of Ischemic Injury

Extracellular Pigments in Ischemic Pouchitis

Shen B, et al. DDW 2009Shen B, et al. DDW 2009

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

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 + +/-

Optical Coherence Tomography for Transmural Inflammation

Normal PouchNormal Pouch

Acute PouchitisAcute Pouchitis

Shen B. DDW 2009

Optical Coherence Tomography for Transmural Inflammation

Chronic PouchitisChronic Pouchitis

Crohn’s PouchCrohn’s PouchPouchPouch

Shen B. DDW 2009

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

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

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

Causes of Fistula/Sinus

Surgical leaksCryptoglandular abscessIatrogenicCrohn’s disease

Surgical leaksCryptoglandular abscessIatrogenicCrohn’s diseaseCrohn s diseaseCrohn s disease

Pouch Vaginal Fistula

Not All Pouch-vaginal Fistulae Are From Crohn’s

Courtesy of Dr. Victor FazioCourtesy of Dr. Victor Fazio

Identification of Internal Os of Fistula

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

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

TreatmentTreatment

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

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

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

Stricture Dilations

Needle Knife “Stricturoplasy”

Shen B. IBDJ 2008

Needle Knife “Fistulotomy”

Pouch-cutaneous Fistula: EndoClip

Natural History and PrognosisNatural History and Prognosis

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)

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

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

Phenotypes of Crohn’s Disease and Pouch Survival

Shen B, et al. IBDJ 2008Shen B, et al. IBDJ 2008

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

7 months

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%

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.

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

Sinus vs. Crohn’s Fistula

Carolyn Roach, PVF Setons