Inflammatory Bowel DiseasesEndoscopy and Imaging

Hans Herfarth, MD, PhDUniversity of North Carolina at Chapel Hill

Chapel Hill, North Carolina

Ulcerative colitis: Definition

Recurrent inflammatory and ulcerating disease of the colon and rectum

Diarrhea, bleeding, crampy abdominal pain,reduced appetite and weight loss

Diffuse inflammation with ulcerations, crypt abscesses, inflammatory infiltrates and reduced number of goblet cells

leftsidedColitis

Progression from rectum to cecum

Proctitis

BackwashIleitis

Pan-Colitis

Crohn’s disease: Definition

Subacute or chronic inflammation of thedigestive tract (mouth to anus)

Crampy abdominal pain, weight loss,diarrhea and fever

Local inflammation with microerosions, fissures, ulcers, granulomas, inflammatory infiltrates and lymphangiectasias

Clinical Symptom in IBDs

Ulcerative colitis

80 %

90 %

47 %

0 %

5 %

1 %

40 %

38 %

11 %

Crohn’s disease

22 %

73 %

77 %

16 %

54 %

35 %

27 %

29 %

10 %

Bleeding

Diarrhea

Abdominal pain

Fistulae

Weight loss

Fever

Anemia

Arthralgia

Iridocyclitis, uveitis

Clinical symptoms

Laboratory findingsMicrobiology findings

Histology

EndoscopyRadiologicImaging

Endoscopy and X-ray small bowel

Gastroscopy

- Staging- Cancer screening- Suspicion of stricture- Need for more intensified therapy

- Staging- Suspicion of

stomach problems

Small Bowel evaluation- Staging- Suspicion of fistulae- Suspicion of stricture

Colonoscopy

Small bowel follow throughCT/MR-enterographyCapsule endoscopy

Normal findings of the ileum and colon

Ascending colonTerminal ileum

Normal findings in the transverse colon

UC - Spectrum of DiseaseUC - Spectrum of Disease

MildMild

ModerateModerate SevereSevere

NormalNormal

CD: spectrum of endoscopic appearances

Inflammatory bowel disease and

the risk of colon cancer

Lower CI

Cumulative risk of CRC1

Upper CI

Copenhagen 1962–972

0

5

10

15

20

25

0 5 10 15 20 25 30

Time from diagnosis (years)

Cum

ula

tive p

robabili

ty (

%)

Eaden et al. 2001; Winther et al. 2001

Cumulative risk of developing colorectal cancer in ulcerative colitis

• Frequency of surveillance colonoscopy not defined,

every 1-2 years suggested

• Ulcerative Colitis

– Extensive disease: 8-10 years after onset

– Left-sided disease: 12-15 years after onset

– Proctitis: not necessary

– Primary sclerosing cholangitis: immediately

• Crohn’s Disease

– Extensive colonic disease: 8-10 years after onset

Recommendations for cancer screening colonoscopy in inflammatory bowel diseases

Small bowel diagnostics

Imaging Modalities in IBD

Per Patient Sensitivity and Specificity

Studies Patients (n)

Sensitivity % [Range]

Specificity % [Range]

Ultrasound 9 1000 90 [78-96] 96[67-100]

Scintigraphy

3 152 88 [76-95] 85 [78-93]

CT 4 113 84 [77-87] 95[67-100]

MRI 7 292 93[82-100]

93[71-100]

Horsthuis et al. 2008

Meta-Analysis of Prospective Studies MRI, CT, Scintigraphy, Ultrasound in IBD

Advantages individual techniques

- MR, CT,(US): extraluminal pathologies.

- US: Cheap and fast

- MR, US: no radiation

- SBFT: information about small bowel motility (adhesions)

Disadvantages individual techniques

- MR, CT, Scintigraphy, PET: no information about small bowel motility

- US: no standardized documentation

- MRI: Acquisition time, costs, availability (!)

Advantages and Disadvantages of Different Imaging Modalities

Possible Diagnostic Approaches for Evaluation of the Small Bowel and Complications of IBD

Major significance 12.1%

Moderate significance

19.7%

Minor significance 68.2%

710 patients with suspected or proven

IBD

Clinical Significance of Extraintestinal Findings in Patients with IBD Detected During MR-

enterography

Herfarth et al. 2009

CT: +840%

SBFT: -65%

Year

Nu

mb

er

of

exam

inati

on

s

Increasing Use of CT-enterography at a Tertiary Referral Center

Peloquin et al. 2008

CT Scans Performed in the United States

Brenner et al. 2007

Radiation Dose for Commonly Used Imaging Studies in Gastroenterology

Annual exposure to environmental radiation: Approx. 3 mSv

Brenner et al. 2003 and 2007

DNA strand breaksMismatch-repair

Threshold effect(cancer risk only above 75-100 mSv)Linear dose-effect relationship?

?

Radiation and Cancer Risk

Risk of Cancer Due To Diagnostic X-ray Exposure

3.2%

1.8%

Berrington de Gonzalez and Darby 2004

Imaging Studies and Cumulative Effective Dose (CED) of Diagnostic Radiation in Crohn’s Disease

Patients

Desmond et al. 2008

15.5%

354 patients Cumulative effective dose range (mSv)

Exp

ose

d p

ati

en

ts [

%]

Cumulative Effective Dose of Diagnostic Radiation over a 15 Years Time Period in Patients with Crohn’s Disease

Desmond et al. 2008

• Analysis of one Claims data base time period 2003-2004 for diagnostic imaging studies in children age 2-18.

• Moderate exposure to diagnostic radiation: 1 CT or 3 fluoroscopic procedures.

Radiation Exposure of Children with IBD in the United States 2003-2004 (Claims Database

Analysis)

Palmer et al. 2009

• CT has evolved as the main imaging modality in IBD with a significant risk of high cumulative doses of diagnostic radiation exposure for IBD patients.

• The long term effects of low dose radiation exposure are still debated.

Summary CT Imaging and Conclusion

We need to

•Better define risk profiles of patients for diagnostic radiation exposure.

•Monitor exposure to radiation in the individual IBD patient.

•Long –term follow up (30-50 years) of IBD cohorts for complications of radiation injury.

We need to

•Better define risk profiles of patients for diagnostic radiation exposure.

•Monitor exposure to radiation in the individual IBD patient.

•Long –term follow up (30-50 years) of IBD cohorts for complications of radiation injury.

Take Home CT- or MR-enterography

• CT-and MR-enterography have a a comparable sensitivity for intestinal pathologies as SBFT

Advantage :

• extraluminal pathologies.

• No radiation (MR)

Disadvantage:

• no information about small bowel motility

Capsule Endoscopy

1. Optical Dom2. Lens holder3. Lens4. LED’s5. Camera6. Batteries7. Transmitter8. Antenna

Dimensions:

Width: 11mm Length: 26mmWeight: 3.7g

Capsule

Comparison Capsule Endoscopy (CE) – CT-enteroclysis (CTE) in IBD

n=41

Voderholzer et al. 2005

CE CTE

Large lesions

8 5

Small lesions

23* 10

*p<0.007

56 patients screened, 15 patients excluded due to suspicion of stricture (27%) !

Case

• Since 13 years Iron deficiency anemia despite iron

supplementation

• Since 10 years recurrent episodes of abdominal cramps

(2 days - 2 weeks duration)

• Multiple endoscopies of the upper and lower GI-tract without

pathological findings

Female patient, 44 years

Clinical examination and Lab results

• 44 years, overweight (155 cm, 72 kg)

• Physical examination unremarkable

Lab results

Hemoglobin (g/dl) 11.4 11.7-15.7

MCV (fl) 75 80-100

MCHC(g/dl) 24 32-36

Iron (µg/dl) 13 50-170

Ferritin (ng/ml) 10.8 10-120

Transferrinsaturation (%) 2 16-45

Clinical work-up

Endoscopy upper GI-tract

MR-Enteroclysis

Ileocolonoscopy (30cm into terminal ileum)

Exclusion of celiac disease (transglutaminase antibodies) and bacterial overgrowth (H2-exhalation test).

negative

Capsule endoscopy

• Multiple ulcerations jejunum (longitudinal)

• Two inflammatory stenoses jejunum

Suspected Crohn´s disease

Therapy and Follow-up

Therapy:

• Budesonide (Entocort®) for 16 weeks

• Iron supplementation orally

Follow-up (4 months): No bowel cramps, normal hemoglogin, no iron supplementation necessary

Problem: Crohn´s disease is only suspected, not proven

Medical history

• Since 10 years diarrhea and constipation, constant pain right

lower abdomen

• PMH: hysterectomy 20 years ago, lysis of adhesions 3 times

(last repair of incarcerated hernia with Marlex mesh 9 years

ago), arthritis, depression, hypertension, type II diabetes,

GERD, obesity

• Upper and lower GI-endoscopy negative, SBFT questionable

irregularities terminal ileum

Female patient, 50 years

Clinical examination and Lab results

• 46 years, overweight (BMI 43)

• Physical examination unremarkable except pain during deep palpation right lower abdomen.

Lab results

Normal range: Hgb, MCV, platelets, ESR.

Capsule endoscopy and NSAIDs

40 volunteers 75 mg Diclofenac 2x daily for 14 days, (+ 20 mg Omeprazol 2 x daily)

Capsule endoscopy and calprotectin - measurementbefore and after 2 weeks of Diclofenac intake

Maiden et al. 2005

Calprotectin elevated 75%

Capsule endoscopy pathologic(Bleeding, Ulceration, Erythema)

68%

Lesions not distinguishable from Crohn’s disease patients

Summary capsule endoscopy

Suspicion of Crohn’s disease• Capsule endoscopy should be performed in cases of negative upper

and lower endoscopy and negative small bowel imaging (SBFT, CT- or

MR-Enterography).

Problem: Verification (Double or single – balloon enteroscopy, )

Proven Crohn’s disease• Capsule endoscopy significantly more sensitive compared to

radiological imaging in detecting inflammatory lesions momentarily no therapeutic consequences!

Except: in cases with “therapy refractory IBD” and negative upper and

lower endoscopy and negative CT or SBFT ( in case of negative result: IBS/IBD!)

Endoscopy in the futureEndoscopy in the future