Capsule endoscopy regional transit abnormality revisited

Capsule endoscopy regional transit abnormality revisited

Brief Reports S-j Tang, S Zanati, E Dubcenco, et al. gastrectomy is recommended for patients with severe, refractory hypoproteinemia and for those w...

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Brief Reports

S-j Tang, S Zanati, E Dubcenco, et al.

gastrectomy is recommended for patients with severe, refractory hypoproteinemia and for those who develop complications such as recurrent bleeding, obstruction, or cancer. It is our proposal that octreotide LAR be considered for treatment of patients with refractory Menetrier’s disease before resorting to surgery. Bryan T. Green, MD M. Stanley Branch, MD Division of Gastroenterology Duke University Medical Center Durham, North Carolina REFERENCES

Figure 1. Endoscopic view of giant folds in gastric body and fundus.

Figure 2. Photomicrograph of biopsy specimen, showing marked foveolar hyperplasia and cystic dilation (H&E, orig. mag. 3200). Octreotide also has been shown to block the effects of epidermal growth factor.8-10 It was postulated by us that this inhibition of epidermal growth factor accounts for the effectiveness of octreotide in treating Menetrier’s disease, and this was the basis for using this drug to treat our patient. The standard formulation of octreotide acetate produced a mild reduction in enteral protein loss in one reported case.10 However, the use of octreotide LAR for Menetrier’s disease has not been reported. Compared with subcutaneous administration of the standard formulation of octreotide acetate three times per day, administration of octreotide LAR once per month is more convenient for patients and likely improves compliance. Partial or total VOLUME 60, NO. 6, 2004

1. Menetrier P. Des polyade´nomes gastriques et de leurs rapports avec le cancer de l’estomac. Arch Physiol Norm Pathol 1888;1:32-55, 236-62. 2. Kovacs AA, Churchill MA, Wood D, Mascola L, Zaia JA. Molecular and epidemiologic evaluations of a cluster of cases of Menetrier’s disease associated with cytomegalovirus. Pediatr Infect Dis J 1993;12:1011-4. 3. Bayerdorffer E, Ritter MM, Hatz R, Brooks W, Stolte M. Menetrier’s disease and Helicobacter pylori [letter]. N Engl J Med 1993;329:60. 4. Meuwissen SG, Ridwan BU, Hasper HJ, Innemmee G. Hypertrophic protein-losing gastropathy: a retrospective analysis of 40 cases in the Netherlands. Scand J Gastroenterol Suppl 1992;194:1-7. 5. Ladas SD, Tassios PS, Malamou HC, Protopapa DP, Raptis SA. Omeprazole induces a long-term clinical remission of protein losing gastropathy of Menetrier’s disease. Eur J Gastroenterol Hepatol 1997;9:811-3. 6. Xiao SY, Hart J. Marked gastric foeveolar hyperplasia associated with active cytomegalovirus infection. Am J Gastroenterol 2001;96:223-6. 7. Burdick JS, Chung EK, Tanner G, Sun M, Paciga JE, Cheng JQ, et al. Brief report: treatment of Menetrier’s disease with monoclonal antibody against the epidermal growth factor receptor. N Engl J Med 2000;343:1697-701. 8. Burghardt B, Barabas K, Marcsek Z, Flautner L, Gress TM, Varga G. Inhibitory effects of long-acting somatostatin analogue on EGF stimulated cell proliferation in Capan-2 cells. J Physiol Paris 2000;94:57-62. 9. Lai HS, Chen Y, Chang KJ, Chen WJ. Effects of octreotide on epidermal growth factor receptor, tissue plasminogen activator, and plasminogen activator inhibitor during intraperitoneal adhesion formation. J Gastroenterol 2003;38:555-60. 10. Yeaton P, Frierson HF Jr. Octreotide reduces enteral protein losses in Menetrier’s disease. Am J Gastroenterol 1993;88: 95-8.

Capsule endoscopy regional transit abnormality revisited Despite initial expectations that capsule endoscopy (CE) would be a highly sensitive test, increasing experience Reprint requests: Norman E. Marcon, MD, Center for Therapeutic Endoscopy and Endoscopic Oncology, Victoria Wing 16-062, St. Michael’s Hospital, Toronto, Ontario, Canada M5B 1W8. Copyright Ó 2004 by the American Society for Gastrointestinal Endoscopy 0016-5107/$30.00 PII: S0016-5107(04)02194-7 GASTROINTESTINAL ENDOSCOPY

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Brief Reports

Figure 2. Resected mid small bowel containing ‘‘apple-core’’ tumor.

Figure 1. Capsule endoscopic view of villous lesion.

indicates that a measurable proportion of lesions are missed. To overcome this problem, a sign, CE regional transit abnormality (RTA), for potential underlying smallbowel pathology is described by us.1 Capsule RTA simply refers to a delay in capsule transit of greater than 15 minutes, with or without a visible mucosal abnormality. Capsule RTA usually is accompanied by mucosal collapse, with prolonged contact between the capsule and the mucosa. A case is described that demonstrates the value of capsule RTA. Potential mechanisms for the false-negative results of CE are discussed.1 Case report. A 68-year-old man was referred because of a 2-year history of obscure-occult GI bleeding, recent weight loss (20 lbs), and vague abdominal pain. The medical history included hypertension and hyperlipidemia. Contrast radiography of the small bowel was normal. CE revealed ‘‘plaques’’ on the small-bowel mucosa that were studded with petechial lesions and lymphangiectasia-like villous lesions.1 Blood was oozing from several of the petechial lesions. Capsule RTA was observed for 22, 25, and 44 minutes in seemingly distinct small-bowel segments with the mucosal ‘‘plaques.’’ The capsule did not fully transit the small bowel by the end of the examination but eventually passed per the anus. Push enteroscopy with a pediatric colonoscope (PCF160L; Olympus America Corp., Melville, N.Y.), with and without spraying of indigo carmine dye, failed to document the CE findings. Random small-bowel biopsy specimens were normal. While the patient was waiting to undergo intraoperative enteroscopy, the anemia and abdominal pain spontaneously resolved, and he regained weight. Because the symptoms had resolved, the patient declined to undergo laparotomy. He agreed to another CE, which revealed more pronounced, protruding villous lesions with papillary projections (Fig. 1). Capsule RTA was again noted; the capsule did not fully transit the small bowel by the end of the examination but eventually passed per the anus. At laparotomy, a constricting tumor found in the mid small 1030

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bowel (Fig. 2) was resected. Intra-operative enteroscopy revealed no other small-bowel lesion. Histopathologic examination of the resection specimen demonstrated an invasive adenocarcinoma. Discussion. The present case is instructive because the first CE revealed only subtle mucosal abnormalities along with capsule RTA, but the mass lesion was missed. At the initial CE, the significance of capsule RTA and the mucosal findings were not appreciated. Moreover, the symptoms and the anemia resolved spontaneously, despite the abnormal finding at a second CE. Thus, this case recapitulates the potential diagnostic value of capsule RTA. The multiple small-bowel lesions seen at two consecutive CEs can only be explained by repetitive images of the same tumor, despite demonstration by the locator program that the capsule traveled through much of the small bowel. Passage of the capsule through the stricture was extremely slow and exceeded the examination time, although in both instances, it eventually passed per the anus. Of the 4 patients in our series with capsule RTA, 3 had underlying small-bowel tumors and a 4th had small-bowel anastomotic varices and presumably an anastomotic stricture as the explanation for the capsule RTA.1 Our 12-month experience with CE was reviewed by us2: capsule RTA was noted in 8 of 50 patients who underwent CE. Six of these 8 patients had underlying small-bowel disorders, giving a positive predictive valve of capsule RTA of 75%. In one of the remaining patients, capsule RTA was attributed to an acute duodenal angulation noted at push enteroscopy. Three patients in our series had a history of bowel surgery; capsule RTA was present in one. This latter patient had small-bowel anastomotic varices, and capsule RTA was presumably because of an anastomotic stricture. Although CE has been in general clinical use for only about 3 years, a relatively short time, false-negative results have been noted in several studies, including several cases of missed small-bowel tumors.3-6 In these cases, visualization of indirect findings eventually led to further investigations and the correct diagnosis, e.g., a second small-bowel tumor at a more distal site,3 or the diagnosis was made by subsequent push enteroscopy.4,5 Pennazio et al.4 reported a case of jejunal tumor that was VOLUME 60, NO. 6, 2004

Brief Reports

S-j Tang, S Zanati, E Dubcenco, et al.

missed by CE but was diagnosed by push enteroscopy. In the case of Lim et al.,5 an oozing jejunal angioectasia missed by CE was diagnosed by push enteroscopy. CE failed to demonstrate an advanced jejunal adenocarcinoma in the patient in the study by Madisch et al.6 The capsule was later found lodged proximal to the tumor, with the optical dome turned backward, as demonstrated by subsequent enteroscopy.6 The field of view of the CE is similar to that of most standard endoscopes (1208 to 1408). Under physiologic conditions, sharply angulated bowel loops and the ileocecal valve can cause capsule RTA. One case is reported in which capsule impaction at the ileocecal valve necessitated surgical removal.7 Many benign conditions, including stricture or diaphragm, adhesions, intra-abdominal or abdominal wall hernia, extrinsic compression, and motility disorder can result in capsule RTA. In patients with gut motility disorders, capsule RTA may be difficult to evaluate.1 Medications that affect gut motility also can be problematic with respect to interpretation of capsule RTA. However, capsule transit will be slowed throughout the small bowel instead of in a specific region, i.e., the transit abnormality does not fit the definition for capsule RTA. Although the explanations for missed lesions at CE are likely numerous, CE, based on current experience, may miss an intrinsic small-bowel abnormality under the following circumstances (Fig. 3): (1) A flat or slightly raised lesion is situated in an angulated bowel loop, and the optical dome of the capsule is directed at the luminal surface opposite the lesion (Fig 3A). This probably explains the failure of CE to visualize the major duodenal papilla in the majority of cases. (2) The lesion is located behind a fold as the capsule advances or is hidden during vigorous peristalsis (Fig. 3B). This would include non-bleeding angioectasia and small lesions, but capsule RTA will not be present. Several cases of small-bowel angioectases that were missed by CE but diagnosed by subsequent push enteroscopy were encountered by us. (3) A significant inflammatory or desmoplastic reaction around a primary small-bowel lesion, e.g., a carcinoid tumor, narrows the proximal small bowel, with only subtle mucosal changes causing RTA (Fig. 3C).1 The bowel lumen may appear dilated, and food debris may or may not be present. (4) The capsule advances with the optical dome facing backward and comes to rest or impacts on an exophytic tumor (Fig. 3D).6 In this circumstances, the capsule visualizes only normal-appearing mucosa, but capsule RTA is present. (5) The lesion is submucosal, and mucosal surface changes, such as ulceration or bleeding, are absent, but capsule RTA is likely if the lesion narrows the lumen. However, even if the surface is ulcerated, CE could miss the lesion because of partial mucosal prolapse when the capsule squeezes through the narrowed lumen, with the ulcerated tumor lying in VOLUME 60, NO. 6, 2004

Figure 3. Diagrammatic representations of circumstances that may account for a false-negative CE. A, Angulated bowel loop. B, Lesion behind fold; lesion hidden during vigorous peristalsis. C, Narrowing of small bowel because of inflammatory or desmoplastic reaction. D, Capsule advances with optical dome facing backward. E, Submucosal lesion. a position parallel to the optical axis of the capsule (Fig. 3E). This mechanism likely explains the false-negative result in a patient with a large, ulcerated stromal tumor.1 In conclusion, the false-negative rate of diagnosis by CE can be minimized by being alert to the occurrence of capsule RTA, although RTA does not always indicate the presence of a significant abnormality. In addition to capsule RTA, the following also should be considered important clues to an underlying abnormality: capsule nonexcretion and dilation of the small bowel, with or without the presence of food debris. If these findings are regarded as abnormal, it may be possible to reduce the frequency of false-negative CE studies. Prospective trials that include patients with and without small-bowel abnormalities are warranted to test the utility of capsule RTA.1 GASTROINTESTINAL ENDOSCOPY

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Shou-jiang Tang, MD Simon Zanati, MD Elena Dubcenco, MD Gregory Monkewich, MD Naveen Arya, MD Maria Cirocco, MSc Gabor Kandel, MD Paul Kortan, MD Gregory B. Haber, MD Norman E. Marcon, MD The Center for Therapeutic Endoscopy and Endoscopic Oncology St Michael’s Hospital University of Toronto Ontario, Canada REFERENCES 1. Tang SJ, Zanati S, Dubcenco E, Christodoulou D, Cirocco M, Kortan P, et al. Capsule endoscopy regional transit abnormality: a sign of underlying small bowel pathology. Gastrointest Endosc 2003;58:598-602. 2. Tang SJ, Christodoulou D, Zanati S, Dubcenco E, Petroniene R, Cirocco M, et al. Capsule endoscopy in obscure gastrointestinal bleeding: single center, one-year experience. Can J Gastroenterol 2004;18:559-65. 3. Ell C, Remke S, May A, Helou L, Henrich R, Mayer G. The first prospective controlled trial comparing wireless capsule endoscopy with push enteroscopy in chronic gastrointestinal bleeding. Endoscopy 2002;34:685-9. 4. Pennazio M, Santucci R, Rondonotti E, Abbiati C, Beccari G, Luchetti R, et al. Wireless capsule endoscopy in patients with obscure gastrointestinal bleeding: results of the Italian multicentre experience [abstract]. Gastrointest Endosc 2002;55: A87. 5. Lim RM, O’Loughlin CJ, Barkin JS. Comparison of wireless capsule endoscopy (M2ATM) with push enteroscopy in the evaluation of obscure gastrointestinal bleeding [abstract]. Am J Gastroenterol 2002;97:S83. 6. Madisch A, Schimming W, Kinzel F, Schneider R, Aust D, Ockert DM, et al. Locally advanced small-bowel adenocarcinoma missed primarily by capsule endoscopy but diagnosed by push enteroscopy. Endoscopy 2003;35:861-4. 7. Mergener K, Schembre DB, Brandabur JJ, Smith MA, Kozarek RA. Clinical utility of capsule endoscopy a single center experience [abstract]. Am J Gastroenterol 2002;97:S299.

Double-balloon enteroscopy through a Roux-en-Y anastomosis for EMR of an early carcinoma in the afferent duodenal limb Endoscopic procedures often are required in patients who have undergone surgical procedures that alter the

Reprint requests: Hironori Yamamoto, MD, Division of Gastroenterology, Department of Internal Medicine, Jichi Medical School, Yakushiji, Minamikawachi, Tochigi, 329-0498, Japan. Copyright Ó 2004 by the American Society for Gastrointestinal Endoscopy 0016-5107/$30.00 PII: S0016-5107(04)02191-1 1032

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Figure 1. Endoscopic view of tumor (arrow) near closed end of duodenal afferent loop.

anatomy of the GI tract. The Roux-en-Y is one such operation. However, the latter procedure makes insertion of an endoscope into the afferent limb technically difficult. A new insertion method of enteroscopy, the double-balloon method, that enables access to the entire small intestine was developed by us.1-3 The double-balloon technique was used to access the afferent duodenal loop in a patient with Roux-en-Y gastrojejunostomy. EMR of an early cancer in the terminal part of the afferent loop was successfully performed. Case report. A 69-year-old man was referred for evaluation of persistent diarrhea and eosinophilia. There was a history of Roux-en-Y gastrojejunostomy for treatment of gastric cancer. No abnormality was found by conventional EGD and colonoscopy. Eosinophilic enteritis was suspected, and enteroscopy was performed by using the double-balloon method. Full informed consent was obtained before the procedure. The new enteroscopy system includes an endoscope with a working length of 200 cm and an outer diameter of 8.5 mm. The endoscope has a built-in air channel directly connected to a soft latex balloon at the tip of the endoscope. The system also includes a flexible 140-cm-long, 12-mm-diameter overtube. The overtube also has a soft latex balloon at the distal end. Both balloons can be inflated or deflated while monitoring balloon pressure. By inflating the overtube balloon enough to grip the intestinal wall, the endoscope can be advanced without forming redundant loops in the small intestine. The endoscope balloon then is inflated, the overtube balloon is deflated, and the overtube is advanced over the enteroscope. By repetition of this sequence, the enteroscope can be inserted deeply into the small intestine. By using this enteroscope/overtube double-balloon system, the end of the duodenal afferent loop was accessed in our patient. A whitish, flat, elevated lesion, 10 mm in length, was found near the closed end of the loop (Fig. 1). Adenocarcinoma was suspected, and biopsy specimens were taken. Although EMR was considered to be indicated, the double-balloon enteroscope (Fuji Photo Optical, Inc., VOLUME 60, NO. 6, 2004