Volume 10, Issue 2, Pages 83-86 (April 2008)

13 of 14

ABSTRACT

FULL TEXT

FULL-TEXT PDF (401 KB)

Utility of Double Balloon Enteroscopy for the Diagnosis and Management of Crohn’s Disease

Crohn’s disease (CD) is a chronic inflammatory bowel disease with an unpredictable clinical course and a high incidence of disease recurrence. It can involve any portion of the gastrointestinal tract, but most commonly is found in the distal small bowel and proximal colon. In 30% of patients, the disease is localized only to the small bowel in which case it may be difficult to diagnose. Double balloon enteroscopy (DBE) now enables direct visualization of most, if not the entire small bowel mucosa, and may facilitate the diagnosis of CD. It also allows for biopsies, which can help differentiate CD from other disorders of the small bowel and may be useful in the dilation of strictures. In this chapter, we discuss the use of DBE for the diagnosis and management of CD.

Keywords: Crohn’s disease, double balloon enteroscopy, small bowel

Article Outline

• Abstract

• Outcomes

• The Role of DBE in the Diagnosis and Long-Term Management of CD

• Therapeutic Role of DBE in the Management of CD

• Summary

• References

• Copyright

Crohn’s disease (CD) can involve any portion of the gastrointestinal (GI) tract, but most commonly is found in the distal small bowel and proximal colon.1, 2, 3, 4 In 30% of patients, the disease is localized only to the small bowel,5, 6, 7 in which case it may be difficult to make the diagnosis. CD, unlike ulcerative colitis (UC), typically causes transmural inflammation that can lead to strictures, fistulas, and abscesses. The mucosal changes of CD disease seen at endoscopy are usually patchy in nature.8 Findings include aphthous ulcerations erosions, nodularity, deep longitudinal ulcers, and stenoses which may be ulcerated8, 9 (Figure 1, Figure 2). Conditions such as enteric infections, mesenteric ischemia, neoplasia, drug-induced enteritis (particularly nonsteroidal anti-inflammatory drugs) may mimic CD endoscopically.10, 11

View Large Image
Download to PowerPoint

Figure 1. CE has become a method of choice to investigate the small bowel in patients with suspected CD. In this patient, CE discloses multiple ulcers and erosions in a patient with clinical and laboratory evidence of CD but negative upper and lower endoscopy as well as small bowel enteroclysis. (Color version of figure is available at www.techgiendoscopy.com.)

View Large Image
Download to PowerPoint

Figure 2. DBE allows for direct mucosal inspection in patients with suspected or known Crohn’s disease. Note the luminal narrowing and the proximal circumferential ulcer, mucosal edema, and erythema (photo courtesy of Lucia C. Fry, MD, Magdeburg, Germany). (Color version of figure is available at www.techgiendoscopy.com.)

There is no single gold standard diagnostic test for CD. CD, like UC, is diagnosed based on a constellation of findings, including the history and physical examination, endoscopic, radiologic, laboratory, and pathology features. Endoscopy plays a critical role in the diagnosis. Ileocolonoscopy can diagnose ileocolonic CD in most cases.12, 13, 14, 15, 16, 17, 18 In patients with CD limited to the small bowel, the inflammatory changes may be out of the reach of ileocolonoscopy or push enteroscopy, and confirming the diagnosis can be challenging.13, 14 A study involving perioperative endoscopy of the small bowel revealed inflammatory lesions evenly distributed between the jejunum and ileum in 65% of patients who underwent surgery for CD.13 Half of these lesions were not detected by preoperative diagnostic studies. Similarly, Boureille and coworkers found that CE detected small bowel lesions outside the reach of ileocolonoscopy in more than two-thirds of patients within 6 months after surgery for CD.14

Video capsule endoscopy (CE) allows for direct visualization of the entire small bowel, but lacks the ability to take biopsies or perform therapeutic interventions.19 Computed tomography (CT) and magnetic resonance (MR) enterography have also aided in the diagnosis.20 A meta-analysis by Triester and coworkers found that CE is superior to all other diagnostic modalities for the diagnosis of nonstricturing small bowel CD in patients with established CD21 (Fig. 1). However, the disadvantage of these noninvasive tests is that they lack the ability to carefully examine the mucosa and take biopsies. The introduction of double balloon enteroscopy (DBE) has made it possible to more closely evaluate the small bowel mucosa and also take biopsies22 (Fig. 2).

Outcomes

The Role of DBE in the Diagnosis and Long-Term Management of CD

Double balloon enteroscopy (DBE) enables visualization of the entire small bowel and allows for biopsies and therapeutic intervention in areas previously out of reach of push enteroscopy or ileocolonoscopy.22, 23, 24 The technical details of the technique have been previously published and also discussed in preceding chapters of this book.23 Visualization of the entire small bowel can be achieved in up to 86% of cases,22, 23, 24 either by an antegrade approach alone or by a combination of antegrade and retrograde approaches.

In an unblinded study, Oshitani and coworkers reported the results of retrograde DBE in 38 patients with established CD.25 Twenty-four patients (63%) had ileal involvement more than 20 cm proximal to the terminal ileum, without any involvement of the distal terminal ileum. In 4 of 18 patients (22.2%), small bowel barium studies failed to identify mucosal changes that were identified on DBE. CE was performed in 8 patients, 1 of whom had mucosal abnormalities not detected by DBE or barium small bowel follow-through. The authors report 2 additional cases of CD presenting with GI hemorrhage diagnosed for the first time by DBE.

As DBE gains wider availability, various groups are publishing their experience and data. Some of the reports include patients in whom the diagnosis of CD was missed by other investigations, but without randomized prospective studies, these reports are difficult to interpret. May and coworkers performed 248 DBEs in 137 patients for a variety of indications.26 Eighteen of the patients had new or established CD, but the diagnostic yield of DBE for the diagnosis of CD, or the route used (antegrade or retrograde) is not reported. In a retrospective study, Matsumoto and coworkers compared antegrade DBE (27 patients) with push enteroscopy (91 patients) and reported a higher diagnostic yield in antegrade DBE (79%) than in push enteroscopy (31%, P = 0.012) for non-bleeding patients without duodenal involvement.27 Some of those cases involved CD. The study is purely descriptive, and no conclusions can be made since patients did not undergo both procedures (push enteroscopy and DBE) for comparison. In other series, investigators have reported similar cases of CD diagnosed by DBE, some which were not diagnosed by other investigations.28, 29 In abstract form, Numata and coworkers reported that DBE had a significant yield (95%) in detecting small bowel CD in patients with established CD and suspected small bowel involvement.30 In another abstract, Kenji and coworkers reported the complementary role of DBE to CE in the diagnosis of small bowel CD and highlighted the fact that 22% of the cases had small bowel disease proximal to the terminal ileum, out of reach of ileocolonoscopy.31

DBE is a relatively safe procedure.24, 29, 32 Although CD causes transmural inflammation, there is no evidence that this translates into a higher risk for perforation during DBE. Stenosis itself is not a contraindication to DBE, but it is helpful to be aware of this before performing the procedure, highlighting the complementary role of radiological procedures, which should be done before DBE.33

DBE could also allow monitoring of mucosal healing in patients with small bowel CD. Studies have clearly indicated a poor correlation of clinical symptoms and mucosal healing of CD after treatment with anti-inflammatory agents.34 Documentation of endoscopic and histologic healing is being increasingly employed as an endpoint to determine efficacy of treatment with immunomodulators and antitumor necrosis factor antibodies.35 Based on pediatric inflammatory bowel disease data, endoscopic healing has been suggested as an objective endpoint to document remission.36

The risk of small bowel adenocarcinoma in CD is estimated to be 17- to 67-fold higher than the general population.37, 38, 39 There are several case reports of small bowel adenocarcinoma developing at the site of stricturoplasty,40 and furthermore, small bowel strictures are a common complication of the mucosal healing process.35 In addition to documenting mucosal healing, DBE may used to take biopsies at stricture sites to exclude malignancy. Finally, DBE may be used as a vehicle for chromoendoscopy and could potentially have a role in the detection of dysplastic lesions in the small bowel.41

Therapeutic Role of DBE in the Management of CD

DBE may also play a role in the therapeutic intervention of small bowel CD, particularly in those patients with strictures. Up to 30% of patients with CD have a stricturing phenotype as defined by the Vienna Classification.42, 43 They may present with symptoms of partial or complete intestinal obstruction. A pressure gradient may also occur across a stenosis, leading to the development of a fistula proximal to the obstruction. Up to 78% of these patients ultimately require surgery.44 Strictures may be treated by stricturoplasty or resection; however, strictures commonly recur and repeated resections may lead to short bowel syndrome.45 Endoscopic balloon dilation (EBD) of fibrotic strictures, either native or anastomotic, in CD is feasible but not without risk. Ferlitsch and coworkers reported their experience in 39 patients in whom 23% has strictures dilated at the ileocolonic anastomosis and 41% at nonsurgical sites. Repeated dilations were required in 62% of patients, and at 36 months, 75% of patients had not required surgery. In a total of 73 dilations, there were 2 perforations.46 Nomura and coworkers reported EBD in 20 patients with CD-related strictures.47 Seven of the patients had anastomotic strictures. Nine patients (56.3%) were able to avoid surgery by 36 months. Perforations occurred in 2 patients. Morini and coworkers reported successful EBD in 34 of 43 patients with ileal or ileocolonic anastomotic strictures in CD. Surgery was avoided in 52.9% of patients after a mean follow-up period of 7 years.48 They reported no major complication.

DBE can also be used for EBD. Sunada and coworkers reported the EBD of strictures in 4 patients during DBE, 2 of whom had CD-related strictures.49 Pohl and coworkers reported on 19 patients with CD and strictures evaluated with DBE.50 In their study, a total of 9 patients could not be treated with EBD because of anatomical reasons or complex stricutres. In the remaining 10 patients, a total of 15 dilations were performed, with 60% of patients achieving symptomatic relief during a median follow-up of 10 months.50 The CRE™ wire guided balloon dilator (Boston Scientific, Natick, MA) has a working length of 240 cm and is long enough to be used with the Fujinon double balloon colonoscope (152 cm) and enteroscope (200 cm). Therefore, DBE has the potential to facilitate the dilation of most CD-related strictures. Larger, prospective studies are still needed to determine the impact on clinical outcomes in these patients.

Summary

Much progress has been made in the ability to examine the small bowel in patients with CD. DBE now enables careful and close examination of most, if not the entire small bowel mucosa. In addition, it allows for biopsies, which can help differentiate CD from other disorders of the small bowel and may be useful in the dilation of strictures. Future studies will need to be done to see if it is a useful technique for monitoring therapy and/or mucosal healing. Finally, it may also prove useful in the ability to monitor for dysplastic mucosal changes.

References

1. 1Stange EF, Travis SP, Vermeire S, et al. European evidence based consensus on the diagnosis and management of Crohn’s disease: definitions and diagnosis. Gut. 2006;55(suppl 1):i1–i15. CrossRef

2. 2Yamamoto T. Factors affecting recurrence after surgery for Crohn’s disease. World J Gastroenterol. 2005;11:3971–3979. MEDLINE

3. 3Decker GA, Loftus EV, Pasha TM, et al. Crohn’s disease of the esophagus: clinical features and outcomes. Inflamm Bowel Dis. 2001;7:113–119. MEDLINE | CrossRef

4. 4Tremaine WJ. Gastroduodenal Crohn’s disease: medical management. Inflamm Bowel Dis. 2003;9:127–128discussion 131. MEDLINE | CrossRef

5. 5Munkholm P. Crohn’s disease: occurrence, course and prognosis (An epidemiologic cohort-study). Danish Med Bull. 1997;44:287–302. MEDLINE

6. 6Mekhjian HS, Switz DM, Melnyk CS, et al. Clinical features and natural history of Crohn’s disease. Gastroenterology. 1979;77:898–906. Abstract | Full-Text PDF (947 KB)

7. 7Steinhardt HJ, Loeschke K, Kasper H, et al. European Cooperative Crohn’s Disease Study (ECCDS): clinical features and natural history. Digestion. 1985;31:97–108. MEDLINE | CrossRef

8. 8Fujimura Y, Kamoi R, Iida M. Pathogenesis of aphthoid ulcers in Crohn’s disease: correlative findings by magnifying colonoscopy, electron microscopy, and immunohistochemistry. Gut. 1996;38:724–732. MEDLINE | CrossRef

9. 9Ge Z-Z, Hu Y-B, Xiao S-D. Capsule endoscopy in diagnosis of small bowel Crohn’s disease. World J Gastroenterol. 2004;10:1349–1352. MEDLINE

10. 10Fefferman DS, Farrell RJ. Endoscopy in inflammatory bowel disease: indications, surveillance, and use in clinical practice. Clin Gastroenterol Hepatol. 2005;3:11–24. Abstract | Full Text | Full-Text PDF (199 KB) | CrossRef

11. 11Lengeling RW, Mitros FA, Brennan JA, et al. Ulcerative ileitis encountered at ileo-colonoscopy: likely role of nonsteroidal agents. Clin Gastroenterol Hepatol. 2003;1:160–169. Abstract | Full Text | Full-Text PDF (877 KB) | CrossRef

12. 12Harewood GC, Mattek NC, Holub JL, et al. Variation in practice of ileal intubation among diverse endoscopy settings: results from a national endoscopic database. Aliment Pharmacol Ther. 2005;15:571–578.

13. 13Lescut D, Vanco D, Bonniére P, et al. Perioperative endoscopy of the whole small bowel in Crohn’s disease. Gut. 1993;34:647–649. MEDLINE | CrossRef

14. 14Bourreille A, Jarry M, D’ Halluin PN, et al. Wireless capsule endoscopy versus ileocolonoscopy for the diagnosis of postoperative recurrence of Crohn’s disease: a prospective study. Gut. 2006;55:978–983. MEDLINE

15. 15Gomez Rodriguez BJ, Ortiz Moyano C, Romero Castro R, et al. Diagnostic yield of 335 push video-enteroscopies. Revista Espanola de Enfermedades Digestivas. 2006;98:82–92.

16. 16Bernstein C, Thorn M, Monsees K, et al. A prospective study of factors that determine cecal intubation time at colonoscopy. Gastrointest Endosc. 2005;61:72–75. Abstract | Full Text | Full-Text PDF (94 KB) | CrossRef

17. 17Marshall JB, Barthel JS. The frequency of total colonoscopy and terminal ileal intubation in the 1990s. Gastrointest Endos. 1993;39:518–520.

18. 18Delmotte JS, Gay GJ, Houcke PH, et al. Intraoperative endoscopy. Gastrointest Endosc Clin North Am. 1999;9:61–69.

19. 19Leighton JA, Triester SL, Sharma VK. Capsule endoscopy: a meta-analysis for use with obscure gastrointestinal bleeding and Crohn’s disease. Gastrointest Endosc Clin North Am. 2006;16:229–250.

20. 20Leighton JA, Loftus EV. Evolving diagnostic modalities in inflammatory bowel disease. Curr Gastroenterol Rep. 2005;7:467–474. MEDLINE | CrossRef

21. 21Triester SL, Leighton JA, Leontiadis GI, et al. A meta-analysis of the yield of capsule endoscopy compared to other diagnostic modalities in patients with obscure gastrointestinal bleeding. Am J Gastroenterol. 2005;100:2407–2418. MEDLINE | CrossRef

22. 22Yamamoto H, Kita H, Sunada K, et al. Clinical outcomes of double-balloon endoscopy for the diagnosis and treatment of small-intestinal diseases. Clin Gastroenterol Hepatol. 2004;2:1010–1016. Abstract | Full Text | Full-Text PDF (248 KB) | CrossRef

23. 23Kita H, Yamamoto H. Double-balloon endoscopy for the diagnosis and treatment of small intestinal disease. Best Pract Res Clin Gastroenterol. 2006;20:179–194. Abstract | Full Text | Full-Text PDF (625 KB) | CrossRef

24. 24Zhong J, Ma T, Zhang C, et al. A retrospective study of the application on double-balloon enteroscopy in 378 patients with suspected small-bowel diseases. Endoscopy. 2007;39:208–215. CrossRef

25. 25Oshitani N, Yukawa T, Yamagami H, et al. Evaluation of deep small bowel involvement by double-balloon enteroscopy in Crohn’s disease. Am J Gastroenterol. 2006;101:1484–1489. MEDLINE | CrossRef

26. 26May A, Nachbar L, Wardak A, et al. Double-balloon enteroscopy: preliminary experience in patients with obscure gastrointestinal bleeding or chronic abdominal pain. Endoscopy. 2003;35:985–991. CrossRef

27. 27Matsumoto T, Moriyama T, Esaki M, et al. Performance of antegrade double-balloon enteroscopy: comparison with push enteroscopy. Gastrointest Endosc. 2005;62:392–398. Abstract | Full Text | Full-Text PDF (216 KB) | CrossRef

28. 28Mönkemüller K, Weigt J, Treiber G, et al. Diagnostic and therapeutic impact of double-balloon enteroscopy. Endoscopy. 2006;38:67–72. CrossRef

29. 29Heine GD, Hadithi M, Groenen MJ, et al. Double-balloon enteroscopy: indications, diagnostic yield, and complications in a series of 275 patients with suspected small-bowel disease. Endoscopy. 2006;38:42–48. CrossRef

30. 30Belluti M, Fry LC, Mönkemüller K, et al. Diagnostic and therapeutic impact of double balloon enteroscopy (DBE) in suspected or known Crohn’s disease (CD). Endoscopy. 2007;39:A382.

31. 31Kenji W, et al: Useful diagnostic strategy in combination capsule endoscopy with double balloon enteroscopy for Crohn’s disease. The 5th International Conference on Capsule Endoscopy 41, 2006

32. 32Ell C, May A, Nachbar L, et al. Push-and-pull enteroscopy in the small bowel using the double-balloon technique: results of a prospective European multicenter study. Endoscopy. 2005;37:613–616. CrossRef

33. 33Sun B, Shen R, Cheng S, et al. The role of double-balloon enteroscopy in diagnosis and management of incomplete small-bowel obstruction. Endoscopy. 2007;39:511–515. CrossRef

34. 34D’Haens G, Geboes K, Rutgeerts P. Endoscopic and histologic healing of Crohn’s (ileo-) colitis with azathioprine. Gastrointest Endosc. 1999;50:667–671. Abstract | Full-Text PDF (1301 KB) | CrossRef

35. 35D’Haens G, Van Deventer S, et al. Endoscopic and histological healing with infliximab anti-tumor necrosis factor antibodies in Crohn’s disease: a European multicenter trial. Gastroenterology. 1999;116:1029–1034. Abstract | Full Text | Full-Text PDF (273 KB) | CrossRef

36. 36Walker-Smith J. Progress in understanding paediatric IBD problems. In: Tytgat GNJ, van Deventer SJH editor. IBD, Report of the Falk Symposium. 1995;p. 329–333Dordrecht, Netherlands.

37. 37Persson PG, Karlén P, Bernell O, et al. Crohn’s disease and cancer: a population-based cohort study. Gastroenterology. 1994;107:1675–1679. Abstract

38. 38Jess T, Loftus EW, Velayos FS, et al. Intestinal and extra-intestinal cancer in Crohn’s disease: follow-up of a population-based cohort in Copenhagen County, Denmark. Aliment Pharmacol Ther. 2004;19:287–293. MEDLINE | CrossRef

39. 39Jess T, Loftus EW, Velayos FS, et al. Risk of intestinal cancer in inflammatory bowel disease: a population-based study from olmsted county, Minnesota. Gastroenterology. 2006;130:1039–1046[see comment]. Abstract | Full Text | Full-Text PDF (153 KB) | CrossRef

40. 40Partridge SK, Hodin RA. Small bowel adenocarcinoma at a strictureplasty site in a patient with Crohn’s disease: report of a case. Dis Colon Rectum. 2004;47:778–781. MEDLINE | CrossRef

41. 41Mönkemüller K, Fry LC, Ebert M, et al. Feasibility of double-balloon enteroscopy-assisted chromoendoscopy of the small bowel in patients with familial adenomatous polyposis. Endoscopy. 2007;39:52–57. CrossRef

42. 42Cosnes J, Cattan S, Blain A, et al. Long-term evolution of disease behavior of Crohn’s disease. Inflamm Bowel Dis. 2002;8:244–250. MEDLINE | CrossRef

43. 43Gasche C, Scholmerich J, Brynskov J, et al. A simple classification of Crohn’s disease: report of the Working Party for the World Congresses of Gastroenterology, Vienna 1998. Inflamm Bowel Dis. 2000;6:8–15. MEDLINE

44. 44Mekhjian HS, Switz DM, Watts HD, et al. National Cooperative Crohn’s Disease Study: factors determining recurrence of Crohn’s disease after surgery. Gastroenterology. 1979;77:907–913. Abstract | Full-Text PDF (754 KB)

45. 45Stebbing JF, Jewell DP, Kettlewell MG, et al. Recurrence and reoperation after strictureplasty for obstructive Crohn’s disease: long-term results. Br J Surg. 1995;82:1471–1474[Published erratum appears in Br J Surg 83:131, 1996]. MEDLINE | CrossRef

46. 46Ferlitsch A, Reinisch W, Püspök A, et al. Safety and efficacy of endoscopic balloon dilation for treatment of Crohn’s disease strictures. Endoscopy. 2006;5:483–487.

47. 47Nomura E, Takagi S, Kikuchi T, et al. Efficacy and safety of endoscopic balloon dilation for Crohn’s strictures. Dis Colon Rectum. 2006;49(suppl):S59–S67. MEDLINE | CrossRef

48. 48Morini S, Hassan C, Lorenzetti R, et al. Long-term outcome of endoscopic pneumatic dilatation in Crohn’s disease. Dig Liver Dis. 2003;35:893–897. Abstract | Full Text | Full-Text PDF (61 KB) | CrossRef

49. 49Sunada K, Yamamoto H, Kita H, et al. Clinical outcomes of enteroscopy using the double-balloon method for strictures of the small intestine. World J Gastroenterol. 2005;11:1087–1089. MEDLINE

50. 50Pohl J, May A, Nachbar L, et al. Diagnostic and therapeutic yield of push-and-pull enteroscopy for symptomatic small bowel Crohn’s disease strictures. Eur J Gastroenterol Hepatol. 2007;19:529–534. CrossRef

Division of Gastroenterology and Hepatology, Mayo Clinic, Scottsdale, AZ.

Address reprint requests to G. Anton Decker, MBBCh, MRCP, Division of Gastroenterology and Hepatology, Mayo Clinic, 13400 East Shea Boulevard, Scottsdale, AZ 85259.

Financial disclosures: Fujinon: research support (GAD, SFP, JAL); Olympus: research support (JAL); Given Imaging: research support and consulting (JAL).

PII: S1096-2883(07)00106-4

doi:10.1016/j.tgie.2007.12.002

13 of 14