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Literature Review

Literature Review. Peter R. McNally, DO, FACP, FACG University of Colorado School of Medicine, Center for Human Simulation Aurora, Colorado 80045. Video Capsule Enteroscopy in the Diagnosis of Celiac Disease: A multicenter Study. Am J Gastroenterol. 2007;102;1624-163.

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Literature Review

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  1. Literature Review Peter R. McNally, DO, FACP, FACG University of Colorado School of Medicine, Center for Human Simulation Aurora, Colorado 80045

  2. Video Capsule Enteroscopy in the Diagnosis of Celiac Disease: A multicenter Study. Am J Gastroenterol. 2007;102;1624-163. Rondonotti E, Spada C, Cave D, Pennazio M, Riccioni M, De Vitis I, Schneider D, Sprujevnik T, Villa F, Langeleir J, Arrigoni A, Costamagna G, de Franchis R.

  3. Rondonotti E, et al. Am J Gastro. 2007;1902:1642-31. Introduction • Celiac Disease (CD) is one of the most common genetic disorders seen in North America. Estimates of prevalence range from 1 in 100-120 persons.1 • The clinical manifestations of CD are many, when CD is full blow is it manifest by diarrhea weight loss, anemia, & malabsorption.2 1. Statement NIH Consensus Development Conference on Celiac Disease http://www.consensus.nih.gov/cons/118/118cdc_intro.htm 2. AGA Institute medical position statement on the diagnosis and management of celiac disease. Gastroenterology. 2006;131;1977-1980.

  4. Rondonotti E, et al. Am J Gastro. 2007;1902:1642-31. • Serologic tests have become the preferred method of screening patients for CD and include: AGA, AmEA, & TTG.3 • “Gold Standard” for the diagnosis of Celiac Disease is identification of Marsh Criteria by small bowel biopsy.2 • Video Capsule Endoscopy (VCE) is a new technology opening a window for “non-invasive” examination of the small intestine. Common VCE findings of Celiac Disease include: scalloping, nodular mucosa, reduced mucosal folds, &/or erosions.5 3. Rostom A, et al. Gastroenterol. 2005;128:S38-S46 5. Korman LY, et al. Endoscopy 2005;37:951-9.

  5. Rondonotti E, et al. Am J Gastro. 2007;1902:1642-31. Aim Test the performance of VCE in patients with both signs/symptoms of and (+) CD serology compared to conventional endoscopy and duodenal biopsy. Determine the longitudinal extent of mucosal involvement of CD beyond the duodenum and its correlation with clinical & serologic markers.

  6. Signs & Symptoms Chronic diarrhea Weight Loss Dermatitis Herpetiformis History of Multiple spontaneous abortions Iron Deficiency Osteoporosis Autoimmune Thyroid Disease Diabetes Mellitus Type I Serologic Tests IgA-AGA 67% (+) IgG-AGA 67% (+) IgA-AmEA 67% (+) IgA-TTG 77% (+) AGA: Antigliadin Antibody AmEA: Endomysial Antibody TTG: TissueTransglutaminase Rondonotti E, et al. Am J Gastro. 2007;1902:1642-31. Study Design:Design: Prospective multi-center enrollment of 43 consecutive subjects with clinical signs and symptoms and at least one positive serologic test (+) for CD.Center Enrollment: 10 Milan, 10 Truin, 15 Rome, 8 Boston Inclusion Criteria: >1 Sign and Symptom (+) >1 serologic Test

  7. Rondonotti E, et al. Am J Gastro. 2007;1902:1642-31. Exclusion Criteria: History Small Bowel Obstruction History Dysphagia Cardiac Pacemaker Electrical Implants Prior gastric/small bowel surgery IgA deficiency Chronic NSAID use or occasional use previous month Study Design:Design: Prospective multi-center enrollment of 43 consecutive subjects with clinical signs and symptoms for and at least one positive serologic test (+) for CD. Center Enrollment: 10 Milan, 10 Truin, 15 Rome, 8 Boston

  8. Rondonotti E, et al. Am J Gastro. 2007;1902:1642-31. Study Design: Diagnostic Procedures • VCE (Given Imaging, Yoqneam, Isreal). • Pill cam swallowed after 12 hr overnight fast • Image analysis using Given Imaging software • Small bowel transit time divided in thirds • Prox 1/3rd • Mid 1/3rd • Distal 1/3rd • EGD’s > 4 biopsies of 2nd portion duodenum: Marsh Criteria on histologic examination

  9. Rondonotti E, et al. Am J Gastro. 2007;1902:1642-31. Study Design: Diagnostic Criteria Biopsy: Marsh Histologic Criteria for CD • Type 0 : normal histology • Type I :  Intraepithelial lymphocytes (IEL) • Type II : crypt hyperplasia + normal villi • Type III : villous atrophy Video Capsule Endoscopy Criteria for CD • Scalloping • Nodular mucosa • Reduced mucosal folds • Erosions

  10. Rondonotti E, et al. Am J Gastro. 2007;1902:1642-31. VCE showing scalloping and nodular mucosa

  11. Rondonotti E, et al. Am J Gastro. 2007;1902:1642-31. VCE showing ulceration (a) and decreased mucosal folds (b) a b

  12. Rondonotti E, et al. Am J Gastro. 2007;1902:1642-31. Demographics

  13. Rondonotti E, et al. Am J Gastro. 2007;1902:1642-31. Results: VCE Changes observed VCE Mucosal Changes N (%) Scalloping 25 (89%) Nodularity – mosaic pattern 12 (43%) Reduction of mucosal folds 10 (35%) Erosions – ulcers 2 (7%)

  14. Rondonotti E, et al. Am J Gastro. 2007;1902:1642-31. Histologic Grading vs. VCE findings

  15. Rondonotti E, et al. Am J Gastro. 2007;1902:1642-31. Serology & VCE vs. Histology

  16. Rondonotti E, et al. Am J Gastro. 2007;1902:1642-31. Result Summary • One of 43 pts with dermatitis herpetiformis & (+) AmEM was Marsh 0 on biopsy, but positive for patchy mucosal changes on VCE. • Four pts with (+) CD serology and Marsh Criteria [(Gr I (1) & Gr III (3)] were negative on VCE (12.5%). • No patients had distal CD changes without coincident proximal VCE mucosal changes. • VCE mucosal changes in distal 1/3rd were only seen with advanced Marsh III changes.

  17. Rondonotti E, et al. Am J Gastro. 2007;1902:1642-31. Conclusion • This study showed that the miss rate for VCE to detect CD among symptomatic, serology and biopsy proven subjects is 4/32 (12%). • VCE identified CD mucosal changes in one subject with Dermatitis Herpetiformis and (+) EMA with biopsy negative CD. Suggesting endoscopic sampling error in 1/43 (2%). • Mucosal changes of CD seen with VCE, always start proximally and tend to predict more advanced Marsh Criteria II & III when the 2nd and 3rd portions of the small bowel exhibit VCE mucosal changes.

  18. Reviewer Comments • Endoscopy and mucosal biopsy remains the gold standard for the diagnosis of CD. However, when biopsies are (-) and clinical suspicion is still high, i.e., (+) EMA & TTG, then VCE may be helpful in identifying subtle, patchy mucosal abnormalities that may support directed mucosal biopsies. • Although VCE changes are common among CD pts (87.5%), the finding in this study that 4 of 32 (12%) CD pts with (+) serologies and Marsh histology have ‘normal’ VCE should emphasize the need for CAUTION as the negative predictive value is 71.4%.

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