1. Comparison of Imaging Modalities for Diagnosing and Monitoring Crohn’s Disease 5-000-485

2. Diagnosing Crohn’s Disease (CD) Diagnosis is based on a comprehensive evaluation of clinical symptoms, small bowel radiology, endoscopy, and laboratory testing of blood, stool, and mucosal tissue (biopsy) 1,2 There is a poor correlation between symptom scores and degree of inflammation 2 Average lag time between onset of symptoms and reaching a diagnosis is 35 months 3 1. CCFA: Crohn’s & Colitis Foundation of America Web site. http://www.ccfa.org/info/about/. 2. Leighton JA et al. Gastrointest Endosc. 2006;63(4):558-565. 3. Mekhjian HS et al. Gastroenterology. 1979;77(4 Pt 2):898-906.

3. Current Practice Imaging Modalities for Crohn’s Disease 1 Small Bowel Follow Through (SBFT)/Small Bowel Enteroclysis Colonoscopy + Ileoscopy (C+I) Computed Tomography (CT) Enterography/CT Enteroclysis Magnetic Resonance (MR) Enterography/MR Enteroclysis Double Balloon Enteroscopy (DBE) Capsule Endoscopy (CE) ASGE practice guidelines recommend that C+I be performed during the initial evaluation of patients with a clinical presentation suggestive of inflammatory bowel disease (IBD) and for differentiating ulcerative colitis (UC) from CD 2 CT plays a relevant role in assessing extra-luminal complications (abscesses) and extra-enteric abnormalities 3 1. Solem CA et al. Gastrointest Endosc. 2008;68(2):255-266. 2. Leighton JA et al. Gastrointest Endosc. 2006;63(4):558-565. 3. Saibeni S et al. World J Gastroenterol. 2007;13(24):3279-3287.

4. Small Bowel Follow Through/Enteroclysis A radiologic examination of the small intestine from the distal duodenum/duodenojejunal junction to the ileocecal valve Advantages Low cost Sensitivity, 85%–95%; specificity, 89%–94% for CD when performed by experienced examiners 1 Can reveal ulcerations, narrowing, and fistulae of the bowel 1 Poor sensitivity and specificity for suspected and mild CD Disadvantages Discomfort of NJC for barium placement Radiation exposure Inability to obtain biopsy or mark abnormalities for surgery CE allows direct visualization of subtle mucosal inflammatory changes or erosions present in early CD that are not commonly seen in barium studies 2 1.Saibeni S et al. World J Gastroenterol. 2007;13(24):3279-3287. 2. Hara AK et al. RadioGraphics. 2005;25:697-718.

5. Colonoscopy With Ileoscopy Direct visualization of the rectum, large intestine, and terminal ileum Advantages More accurate than barium x-rays in detecting small ulcers or areas of inflammation Ability to obtain a biopsy sample or mark abnormalities for surgery Disadvantages Invasive Requires a colon preparation Inability to visualize the small bowel (ileum only) Contraindicated in severe colitis or toxic megacolon ASGE practice guidelines recommend that C+I be performed during the initial evaluation of patients with a clinical presentation suggestive of IBD and for differentiating UC from CD Endoscopy together with other diagnostic modalities can differentiate CD from UC in ≥85% of patients Leighton JA et al. Gastrointest Endosc. 2006;63(4):558-565.

6. Mucosal biopsy is a critical component of endoscopic examination for patients with suspected IBD to differentiate IBD from other colitis, such as bacterial infection, ischemia, and NSAID use, as well as to differentiate CD from UC Mucosal biopsy helps to establish the extent of colon that is inflamed, which aids in determining prognosis, directing appropriate therapy, and stratifying risk for dysplasia Determination of extent of colitis should be based on histologic examination rather than on endoscopy However, the frequency of detection of granulomata varies from 15% to 36% of endoscopic biopsy specimens, and granulomas are not characteristic for CD Specimens should be taken from the edges of multiple ulcers and aphthous erosions and from normal-appearing mucosa Mucosal Biopsy Leighton JA et al. Gastrointest Endosc. 2006;63(4):558-565.

7. Capsule Endoscopy Helps Guide Management When Endoscopy and Histology Findings Are Discordant 129 CE cases for suspected CD were reviewed A discordant finding was defined as a normal endoscopy with abnormal biopsy, or the converse Findings were consistent with CD for 63 patients Of the 63 patients with CD, 30 patients had complete colonic and ileal data with biopsy results Discordance between histology and endoscopy occurred for 17% of patients with both endoscopy and biopsy results The locations of the CE findings were 23% in the jejunum, 23% in the ileum, and 54% in both areas of the small bowel CE was helpful in guiding management when the endoscopy and histology results did not agree Shepela C et al. Gastrointest Endosc. 2009;69(5):AB287.

8. Computed Tomography (CT) Enterography/Enteroclysis Computerized radiologic procedure used for the detection of intra-abdominal abscesses, strictures, pre-stenotic dilatations, fistulae CT plays a relevant role in assessing extra-luminal complications (abscesses) and extra-enteric abnormalities Findings observed in CD include small bowel wall stratification and/or thickening, edema of the mesenteric fat, engorged ileal vasa recta, submucosal fibro-fatty infiltration, and mesenteric adenopathy Advantages Comprehensive structural assessment of the abdomen, pelvis, and small bowel Sensitivity, 71%–83%; specificity, 90%–98% for CD 1 Disadvantages Discomfort of nasojejunal catheter (NJC) for barium placement Exposure to radiation: 1.5%-2% of all cancers in the U.S. may be attributed to radiation from CT studies Inability to obtain biopsy or mark abnormalities for surgery Ability to assess disease activity unclear Saibeni S et al. World J Gastroenterol. 2007;13(24):3279-3287. Brenner DJ et al. N Engl J Med. 2007;357(22):2277-2284.

9. Capsule Endoscopy and Computed Tomography Are Complementary CT has specific roles in determining the extent of established small bowel CD CE gives unparalleled depiction of the mucosal surface of the small bowel CT may help establish the presence of strictures and determine if CE can be used safely to show extent of disease Maglinte D et al. Radiology. 2007;245(3):661-671.

10. Magnetic Resonance (MR) Enterography/Enteroclysis Non-ionizing radiation diagnostic technique; able to obtain multi- planar diagnostic information about intra- and extra-mural involvement of the small bowel 1 Good correlation between the degree of wall enhancement after intravenous (IV) contrast injection and disease activity (calculated using Crohn’s Disease Activity Index) has been obtained, with overall high specificity for MR findings Advantages Comprehensive structural assessment of the abdomen, pelvis, and small bowel >80% sensitivity and specificity for CD 1 Disadvantages Discomfort of nasojejunal catheter for barium placement Inability to obtain biopsy or mark abnormalities for surgery Expensive 1. Saibeni S et al. World J Gastroenterol. 2007;13(24):3279-3287.

11. Double Balloon Endoscopy Also known as “push and pull enteroscopy,” a balloon at the end of a special enteroscope camera and an overtube is inserted through the mouth and passed into the small bowel. Using the assistance of friction at the interface of the enteroscope and intestinal wall, the small bowel is accordioned back to the overtube. The overtube balloon is then deployed, and the enteroscope balloon is deflated. The process is continued until the entire small bowel is visualized Advantages Allows complete endoscopic evaluation of the small bowel 1 Ability to obtain a biopsy sample 1 Able to carry out therapeutic interventions along the entire small bowel 1 Disadvantages Inconvenient and invasive Requires specialized equipment, sedation, fluoroscopy, and prolonged examination time 1 1. Saibeni S et al. World J Gastroenterol. 2007;13(24):3279-3287.

12. Capsule Endoscopy Swallowable wireless video capsule that transmits images during passive movement through the GI tract Advantages Non-invasive, painless, disposable Permits direct visualization and high-resolution images of the entire small bowel 1 May help identify superficial lesions not detected by traditional endoscopy and radiology 2 Sensitivity 93%; specificity 84% for CD 1 Disadvantages Inability to obtain biopsy or mark abnormalities for surgery 2 Contraindicated when strictures are suspected (risk of capsule retention) and in patients with swallowing difficulty or who use pacemakers or other implanted electromedical devices 1,3 Historic concern over high sensitivity with low specificity 1. Saibeni S et al. World J Gastroenterol. 2007;13(24):3279-3287. 2. Leighton JA. Gastrointest Endosc. 2006;63(4):558-565. 3. Hara AK et al. RadioGraphics. 2005;25:697-718.

13. The Value of Capsule Endoscopy in Suspected Crohn’s Disease In patients in whom a case of CD is suspected (newly diagnosed disease), CE has a low retention rate of 1%–2% and a higher diagnostic yield than small bowel barium studies, conventional CT, CT enteroclysis, or CT enterography 1 After negative colonoscopy and ileoscopy findings, CE is considered to be the first-line examination in the investigation of suspected non- stricturing CD 1 1. Maglinte D et al. Radiology. 2007;245(3):661-671.

14. Imaging Modalities Key Points Diagnosis of CD is based on an evaluation of symptoms, small bowel radiology, endoscopy, and laboratory testing of blood, stool, and biopsy Radiology examinations (SBFT) have poor sensitivity in the detection of early inflammatory lesions 1 CT and CE are complementary in identifying findings associated with CD A rough approximation of radiation exposure from 1 abdomen pelvis CT in an adult is equal to 100 to 250 chest x-rays 2 Endoscopy is limited to the most distal and proximal portion of the small bowel1 Granulomas (biopsy) are not characteristic for CD (ASGE) 1. Triester SL et al. Am J Gastroenterol 2006;101(5):954-964. 2. GIST Support International. www.gistsupport.org. Accessed July 9, 2009.

15. Imaging Modalities Key Points: Capsule Endoscopy Considered standard practice in investigating diseases of the small intestine 1,2 Useful for differentiating Crohn’s disease (CD) from ulcerative colitis (UC) or indeterminate colitis (IC), for detecting recurrences, for establishing extent of disease, and for assessing response to therapy 3 Allows the detection of small bowel changes that are not within reach of push enteroscopy 3 Allows direct visualization of the small bowel, and can detect subtle mucosal inflammatory changes or erosions present in early CD that are not commonly seen in barium studies 1. Saibeni S et al. World J Gastroenterol. 2007;13(24):3279-3287. 2. Westerhof J et al. Minerva Gastroenterol Dietol. 2008;54(2):189-207. 3. Leighton JA et al. Gastrointest Endosc. 2006;63(4):558-565.