- Email: [email protected]
Diagnostic yield and clinical outcomes of capsule endoscopy
Diagnostic yield and clinical outcomes of capsule endoscopy Amit Rastogi, MD, Robert E. Schoen, MD, MPH, Adam Slivka, MD, PhD Pittsburgh, Pennsylvania
Background: Capsule endoscopy is proving to be superior to push enteroscopy and barium contrast radiography for evaluation of the small bowel. However, its impact on clinical outcome has not been thoroughly investigated. This study assessed changes in therapy based on capsule endoscopy findings and on the impact of such changes on patient outcomes. Methods: Forty-four consecutive capsule endoscopies in 43 patients were reviewed. Data were collected by systematic review of patient records and included indication, results of prior diagnostic tests, and capsule endoscopy findings. Specific interventions after capsule endoscopy and clinical outcome were noted. Results: The indication for capsule endoscopy was obscure GI bleeding in 40 patients, iron deficiency anemia in one, and right lower quadrant abdominal pain in two patients. Overall diagnostic yield was 42% (18/43 patients). Diagnostic findings included angiodysplasias (n = 13), intestinal ulcers (n = 2), Crohn’s disease (n = 2), and mass lesion (n = 1). As a result of the capsule endoscopy findings, a specific intervention was implemented in 12 of 18 patients with positive findings. These included endoscopy with coagulation (n = 5), laparotomy (n = 2), pharmacotherapy (n = 4), and discontinuation of medication (n = 1). At a mean follow-up of 6.7 months, the clinical outcome was considered positive in 7 of 43 patients (16%). Conclusions: Although it has a high diagnostic yield, capsule endoscopy has a positive influence on clinical outcome in a relatively small proportion of patients. Larger studies are needed that assess the influence of capsule endoscopy on clinical outcomes. (Gastrointest Endosc 2004;60:959-64.)
Capsule endoscopy (CE) is a major advance in visualization of the small intestine. Conventional modalities for examination of the small bowel, including barium contrast radiography, enteroclysis, push enteroscopy, Sonde endoscopy, and intraoperative enteroscopy, all have significant limitations.1-8 Since the introduction of CE,9 the indications for the procedure have expanded to include Crohn’s disease, celiac disease, polyposis syndromes, monitoring of patients after small-bowel transplantation, and unexplained abdominal pain, in addition to obscure GI bleeding (OGIB). Thus, the initial studies of CE focused on diagnostic yield, in which respect CE has been shown to be superior to push enteroscopy and barium contrast radiography.5,10-12 However, there are few studies that assess the impact of CE on clinical outcome, so that the true value of this novel technology is less well established. In particular, long-term patient follow-up was not included in most studies. The present study, therefore, evaluated the
Received April 27, 2004. For revision July 8, 2004. Accepted August 17, 2004. Reprint requests: Adam Slivka, MD, PhD, 200 Lothrop St., Mezzanine Level, C-Wing, Pittsburgh, PA 15213. Copyright Ó 2004 by the American Society for Gastrointestinal Endoscopy 0016-5107/$30.00 PII: S0016-5107(04)02226-6 VOLUME 60, NO. 6, 2004
influence of CE on therapy and its impact on patient outcomes. PATIENTS AND METHODS A total of 44 consecutive CEs (43 patients) performed at a single institution were evaluated retrospectively. To be eligible for CE, patients were required to have undergone an upper endoscopy, colonoscopy, and barium contrast radiography of the small bowel. Contraindications were the following: pregnancy, symptoms/signs of bowel obstruction, and an implanted pacemaker. CE was performed after an overnight fast. Ingestion of clear liquids was permitted 4 hours after swallowing the capsule. Recording of the CE was disconnected after 8 hours. The capsule images were interpreted by one of two gastroenterologists. The medical records of all patients were reviewed in a detailed, systematic fashion. The indication for CE, the duration of symptoms before CE, and the blood transfusion requirement were noted. The results of all diagnostic tests obtained before CE, including upper endoscopy, colonoscopy, push enteroscopy, contrast radiography, scintigraphy (tagged red blood cell), mesenteric angiography, and CT were noted. Specific interventions based on the CE findings were identified by scrutinizing the medical record and by contacting primary care physicians. Details of post-CE interventions, including endoscopy with endotherapy, surgery, pharmacotherapy, and discontinuation of medication, were noted. The patient and the primary care physician were contacted to assess the current medical status of the patient and to determine whether any GASTROINTESTINAL ENDOSCOPY
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Diagnostic yield and clinical outcomes of capsule endoscopy
Table 1. Indication of capsule endoscopy
Table 2. Diagnostic yield of capsule endoscopy
Indication for capsule endoscopy
Findings
Obscure overt GI bleeding Obscure occult GI bleeding Iron deficiency anemia Right lower quadrant pain
No. patients (%) 22 18 1 2
(51%) (42%) (2%) (5%)
clinical intervention occurred at another facility. A successful clinical outcome was defined as the following: (1) resolution of symptoms and/or (2) normalization of the blood test(s) that prompted CE. Statistical analysis was performed by using the Fisher exact test. A p value <0.05 was considered statistically significant.
RESULTS A total of 44 CE procedures were performed in 43 patients (25 men, 18 women; mean age 56 years, range 24-86 years) from December 2001 to October 2002. The indication for CE was OGIB in 40 patients (93%); iron deficiency anemia in one patient (2%); and right lower quadrant abdominal pain, with a clinical suspicion of Crohn’s disease in two patients (5%) (Table 1). OGIB was defined as bleeding of unknown origin that persists or recurs, with no source detected by conventional evaluation, including endoscopy or contrast radiography. OGIB was further subdivided into overt (melena or hematochezia) (22 patients, 51%) and occult (positive tests for fecal occult blood) (18 patients, 42%). All patients had undergone an extensive evaluation before CE: a total of 82 upper endoscopies (range 1-4), 86 colonoscopies (range 0-10), and 54 push enteroscopies (range 0-3) were performed. One patient had undergone colectomy and ileostomy for ulcerative colitis. All patients had undergone barium contrast radiography of the small bowel before CE. All of the latter studies were negative; specifically, no stricture or mass lesion was demonstrated. Among the 43 patients, additional investigations included CT of the abdomen (n = 20), tagged-red-blood-cell scintigraphy (n = 14), a scan for Meckel’s diverticulum (n = 1), and mesenteric angiography (n = 7). Median duration of complaints before CE was 8 months (range 1 week to 15 years). Of the 40 patients with OGIB, 37 had an ongoing requirement for blood transfusion (range 2-30 units). CE was performed in every patient without complication. CE was incomplete in 22 patients (50%) because the capsule did not traverse the entire length of the small intestine before termination of the study (after approximately 8 hours). In one patient, the capsule remained lodged at the gastroesophageal junction until the battery was drained; the patient remained asymptomatic. In another patient who had 960
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No. patients
Angiodysplasias Duodenum Jejunum/ileum Jejunal ulcer Ulcer at ileocolonic anastomosis Ulceration with cobblestoning and stricturing Mass lesion
6 7 1 1 2 1 18 of 43 (42%)
undergone small-bowel transplantation, the capsule remained in the stomach for the entire examination period. CE was repeated with intravenous administration of metoclopramide (5 mg) and endoscopic placement of the capsule in the duodenum and resulted in visualization of the entire small intestine. For two CEs, the length of small intestine visualized was indeterminate. The mean time for capsule transit of the small intestine in patients in whom the entire length was visualized was 313 (78) minutes. For the incomplete studies, the mean length of time during which images were captured was 466 (28) minutes. Eleven of the 44 CEs (25%) were considered to be suboptimal because of fluid and solid debris in the small intestine. However, all examinations are included in the analysis. In 8 of the 11 suboptimal examinations, the capsule did not reach the end of the small bowel (incomplete examination). The most frequent capsule diagnosis was angiodysplasia of the small intestine (n = 13). In 7 patients, the angiodysplasias were found in the jejunum or ileum; in 6, they were in the duodenum. Oozing of blood from angiodysplasias in the duodenum was seen in 5 patients and from angiodysplasias in the terminal ileum in one patient. One patient with ulceration of the jejunum was taking a nonsteroidal anti-inflammatory drug (NSAID). One patient with a history of partial ileal resection and ileocolonic anastomosis had an ulcer with a red spot on the ileal side of the anastomosis. Ulceration, cobblestoning, and stricturing in the small bowel suggestive of Crohn’s disease were found in two patients. In one of the latter, blood was oozing from an ulcer. One patient with a history of renal-cell carcinoma had a mass in the proximal small bowel. The overall diagnostic yield (Table 2) was 42% (18 patients). Outcome The impact of CE on clinical outcome is summarized in Table 3. Of the 7 patients with VOLUME 60, NO. 6, 2004
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Table 3. Interventions based on findings of capsule endoscopy and patient outcome Finding Duodenal angiodysplasia Actively oozing Not oozing Jejunal/ileal angiodysplasia Actively oozing
Not oozing
No. patients
Intervention
5
Repeat endoscopy and coagulation None
Normalization of Hb in 2 patients None
Laparotomy and intra-operative enteroscopy Hormone therapy
Normalization of Hb
1 1
3
Not oozing Jejunal ulcer Ulcer at ileocolonic anastomosis
3 1 1
1
None NSAID stopped Laparotomy, intra-operative enteroscopy and resection Treated with mesalamine None
Ulceration, cobblestoning and stricturing Ulceration, cobblestoning and stricturing Mass lesion
1
1
None
Positive outcome
Normalization of Hb in 1 patient None No further GI blood loss Normalization of Hb
Resolution of blood loss and diarrhea None None
NSAID, Non-steroidal anti-inflammatory drug.
angiodysplasias in the jejunum or ileum, only one had a lesion that was seen to be bleeding. This was an ileal angiodysplasia, and the patient underwent laparotomy, with confirmation of the CE finding by intra-operative enteroscopy and subsequent bowel resection. After an uneventful postoperative recovery, the bleeding resolved and the hematocrit normalized. Three of the 6 patients with nonactively oozing angiodysplasias were treated by hormone replacement; only one of these patients responded with normalization of the hematocrit and no further transfusion. Hormone therapy was refused by two patients and was contraindicated in one other patient. Of the 7 patients with angiodysplasias in the jejunum or the ileum, 5 had continuing blood loss and anemia. Of the 6 patients with duodenal angiodysplasia, the 5 with active bleeding (oozing) at CE underwent upper endoscopy with identification of the lesions in all cases. In two patients, use of a side-viewing duodenoscope was required for localization. The angiodysplasias were treated by multipolar electrocoagulation. However, on followup, only two patients had stabilization of the hematocrit, with no further transfusion requirement. One patient with a non-oozing angiodysplasia in the duodenum refused further endoscopy and hormone replacement therapy and remained anemic. The patient with ulceration in the jejunum discontinued NSAID use, after which there was no further evidence of GI blood loss. In the patient with an ulcer VOLUME 60, NO. 6, 2004
with a red spot at the ileocolonic anastomosis, exploratory laparotomy with intra-operative enteroscopy confirmed the findings. Active bleeding was present at surgery, and the anastomotic segment was resected. After postoperative recovery, the hematocrit normalized, and there was no further evidence of bleeding. In two patients, the CE findings were suggestive of Crohn’s disease. One was treated with a mesalamine preparation, and the GI blood loss and diarrhea resolved. The other patient declined treatment and remained anemic, with occult GI blood loss. The patient with a history of renal cancer and a mass in the small bowel died 6 weeks after CE. A specific intervention or change in management based on the CE findings was implemented in 12 patients (28%). At a mean follow-up of 6.7 months, a clinically meaningful change in outcome had occurred in 7 patients (16%). Diagnostic yield and outcome in patients with obscure overt vs. obscure occult bleeding Of the 22 patients with obscure overt bleeding, 8 (37%) had a positive finding on CE compared with 10 of 18 patients (56%) with obscure occult bleeding (p = 0.34). A positive clinical outcome was observed in 5 of 22 patients (23%) with obscure overt bleeding and two of 18 patients (11%) with obscure occult bleeding (p = 0.43). Of the patients with a positive finding on CE, a positive outcome was noted in 5 of GASTROINTESTINAL ENDOSCOPY
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8 patients with overt bleeding and two of 10 patients with occult bleeding (p = 0.14). DISCUSSION Most published studies of CE are focused on diagnostic yield, which ranges from 45% to 70%.5,10-14 This is superior to barium contrast radiography11 and push enteroscopy.5,10-12 In one study, the diagnostic yield of CE was 45% compared with 20% for contrast radiography.11 For the indication OGIB, contrast radiography had a diagnostic yield of 5% vs. 31% for CE (p < 0.05). In the study of Lewis and Swain,10 the yield of CE was 55% compared with 30% for push enteroscopy. Because there is no reference standard, the true sensitivity and specificity of CE cannot be determined. Diagnostic yield, although important, can be misleading, given the discovery of potentially non-specific findings: it is frequently difficult to differentiate a true from a false-positive finding or a true-negative from a false-negative finding.15 This is especially the case with angiodysplasias, the most common diagnostic finding at CE. It often is difficult to be certain that a small red spot on the mucosa is really an angiodysplasia; even if it is, it is also difficult to know whether it is the actual source of bleeding. Similarly, it is challenging to differentiate a small, possibly temporary mucosal break of no clinical importance from an ulcer that is clinically significant. Thus, it is more meaningful to assess the value of CE in relation to changes in management and clinical outcomes. The present retrospective study assessed the impact of CE on clinical management and patient outcome. The diagnostic yield was 42% (18 of 43 patients), the most common finding being angiodysplasias (13 of 18 patients). Based on CE findings, a specific intervention was implemented in 12 of 18 patients with a positive CE finding, and a positive clinical outcome was noted in 7 (16%). There was no statistically significant difference in diagnostic yield and outcome of CE in patients with overt vs. those with occult bleeding. Few studies have focused specifically on clinical outcome or long-term follow-up of patients undergoing CE. In the series of Lewis and Swain,10 CE led to surgical resection of a small-bowel segment in 4 patients with OGIB. Further transfusion was not required in one of these patients, but no follow-up was given for the other 3. In a study that included 20 patients, Adler et al.12 reported follow-up for 6 patients, 5 of whom had resolution of bleeding. Other studies, preliminarily reported in abstract form alone,16-22 have followed 22 to 53 patients; diagnostic yields range from 37% to 77%. In these 962
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Diagnostic yield and clinical outcomes of capsule endoscopy
studies, management was changed or the clinical outcome was said to be improved in 17% to 63% of cases. In a study23 of 100 patients with OGIB, CE yielded a ‘‘definite’’ positive finding in 92.3% of patients with ongoing overt bleeding, in 12.9% of those with previous overt bleeding, and in 44.2% of those with obscure occult bleeding. Bleeding resolved more frequently in patients with ongoing overt and occult bleeding compared with patients with previous overt bleeding. Outcome was reported as improved in a high proportion of patients, but, in some cases, this was not attributable to interventions based on CE findings. In addition to the relatively small number of patients, limitations of the present series include the following: failure of 50% of the examinations to visualize the entire small intestine and suboptimal visualization in 25% because of retained fluid and solid debris. Thus, significant lesions could have been missed in the terminal ileum or obscured by retained material. If these problems could have been averted, the diagnostic yield and the number of patients with improved clinical outcomes might have been higher. In 50% of the examinations, the capsule had not reached the end of the small intestine at termination of the procedure (about 8 hours). Preliminarily reported data indicate that the administration of erythromycin, which expedites gastric emptying, increases the likelihood that the entire small bowel will be visualized during transit of the capsule.24 Improved battery life with lengthening of the time available for imaging also could minimize this shortcoming. Whether a bowel preparation improves visualization of the small-bowel mucosa also is an important issue. Visualization was classified as suboptimal for 25% of the CEs in the present series because of the presence of fluid and solid debris in the small intestine. Polyethylene glycol has been administered as a bowel preparation before CE.25-27 In a preliminary report of a prospective, blinded study, O’Loughlin et al.27 noted that administration of polyethylene glycol on the day before CE significantly improved small-bowel visualization. In the study of Lewis and Swain,10 patients drank a simethicone solution before ingestion of the capsule. Albert et al.28 found that administration of simethicone reduced the presence of intraluminal bubbles and thereby significantly improved visualization. Six patients (14%) in the present series had angiodysplasias in the duodenum that were within reach with an upper endoscope or enteroscope. These lesions were missed at prior endoscopies. In the study of Costamagna et al.,11 30% of patients had lesions in the proximal small intestine, within VOLUME 60, NO. 6, 2004
Diagnostic yield and clinical outcomes of capsule endoscopy
reach of an upper endoscope, that had been missed at endoscopy. No complication because of ingestion of the capsule was encountered in the present study. In one patient, the capsule lodged at the gastroesophageal junction until the battery was drained. Lodgement did not result in any untoward effect. A radiograph of the abdomen 2 days later revealed that the capsule had passed. Although few complications of CE have been reported, Mergener et al.29 encountered prolonged retention of the capsule in 7 of 197 examinations, including small-bowel obstruction in one patient. Two capsules were extracted endoscopically, and surgery was required for removal of 5. In another study, small-bowel obstruction occurred in two of 200 patients undergoing CE.30 Because the use of CE is increasing, further prospective studies of the associated complications are clearly needed. OGIB remains the leading indication for CE. Other potential indications include Crohn’s disease,31-33 celiac disease, familial polyposis syndromes, AIDS, monitoring of small-bowel transplantation patients, and unexplained abdominal pain. The rapidly expanding use of CE in patients with unexplained abdominal pain as a means of ruling out Crohn’s disease raises certain concerns. Because CE is highly sensitive for tiny mucosal breaks, it is likely to have a much higher diagnostic yield compared with contrast radiography. However, it is presently unknown whether such findings are caused by Crohn’s disease and/or whether their discovery will contribute substantially to improved patient outcomes. As demonstrated by the present study, patient outcomes are a much more relevant standard for assessment of CE than diagnostic yield. Further study of the actual clinical impact of CE is clearly needed. REFERENCES 1. Foutch PG. Angiodysplasia of the gastrointestinal tract. Am J Gastroenterol 1993;88:807-18. 2. Nolan DJ, Traill ZC. The current role of the barium examination of the small intestine. Clin Radiol 1997;52:809-20. 3. Maglinte DD, Kelvin FM, O’Connor K, Lappas JC, Chernish SM. Current status of small bowel radiography. Abdom Imaging 1996;21:247-57. 4. Batram CI. Small bowel enteroclysis: cons. Abdom Imaging 1996;21:245-6. 5. Appleyard M, Fireman Z, Glukhovsky A, Jacob H, Shreiver R, Kadirkamanathan S, et al. A randomized trial comparing wireless capsule endoscopy with push enteroscopy for the detection of small bowel lesions. Gastroenterology 2000;119:1431-8. 6. Swain P. The role of enteroscopy in clinical practice. Gastrointest Endosc Clin N Am 1999;9:135-44. 7. Seensalu R. The Sonde exam. Gastrointest Endosc Clin N Am 1999;9:37-59. VOLUME 60, NO. 6, 2004
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8. Zaman A, Sheppard B, Katon RM. Total peroral intraoperative enteroscopy for obscure GI bleeding using a dedicated push enteroscope: diagnostic yield and patient outcome. Gastrointest Endosc 1999;50:506-10. 9. Iddan G, Meron G, Glukhovsky A, Swain P. Wireless capsule endoscopy. Nature 2000;405:417. 10. Lewis BS, Swain P. Capsule endoscopy in the evaluation of patients with suspected small intestinal bleeding: results of a pilot study. Gastrointest Endosc 2002;56:349-53. 11. Costamagna G, Shah SK, Riccioni ME, Foschia F, Mutignani M, Perri V, et al. A prospective trial comparing small bowel radiographs and video capsule endoscopy for suspected small bowel disease. Gastroenterology 2002;123: 999-1005. 12. Adler DG, Knipschield M, Gostout C. A prospective comparison of capsule endoscopy and push enteroscopy in patients with GI bleeding of obscure origin. Gastrointest Endosc 2004;59:492-8. 13. Eu 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. 14. Scapa E, Jacob H, Lewkowicz S, Migdal M, Gat D, Gluckovsky A, et al. Initial experience of wireless capsule endoscopy for evaluating occult gastrointestinal bleeding and suspected small bowel pathology. Am J Gastroenterol 2002;97:2776-9. 15. Faigel DO, Fennerty MB. ‘‘Cutting the cord’’ for capsule endoscopy. Gastroenterology 2002;123:1385-8. 16. Chong A, Taylor A, Miller A, Desmond P. Clinical outcomes following capsule endoscopy (CE) examination of patients with obscure gastrointestinal bleeding (OGB) [abstract]. Gastrointest Endosc 2003;57:AB166. 17. Guda N, Molloy R, Carron D, Gleisner M, Vakil N. Does capsule endoscopy change the management of patients? [abstract]. Gastrointest Endosc 2003;57:AB167. 18. Sacher-Huvelin S, Barouk J, Rhun ML, Des Varannes SB, Galmiche JP. Wireless capsule endoscopy of the small intestine: does it really impact the management strategy? [abstract]. Gastrointest Endosc 2003;57:AB167. 19. Delvaux M, Fassler I, Gay G. Obscure digestive bleeding (ODB): validation of a diagnostic strategy integrating capsule enteroscopy (CE) as first line intestinal investigation [abstract]. Gastrointest Endosc 2003;57:AB162. 20. Chutkan R, Toubia N, Balba N. Findings and follow-up of the first 125 video capsule patients at Georgetown University Hospital [abstract]. Gastrointest Endosc 2003;57: AB85. 21. Ciorba M, Jonnalagadda S, Zuckerman G, Stone C, Prakash C. Capsule endoscopy: varied outcomes over short-term follow-up [abstract]. Gastrointest Endosc 2003;57:AB167. 22. Leighton J, Sharma V, Malikowski M, Fleischer D. Long term clinical outcomes of capsule endoscopy (CE) in patients with obscure gastrointestinal bleeding (OGIB) [abstract]. Am J Gastroenterol 2003;98:S300. 23. Pennazio M, Santucci R, Rondonotti E, Abbiati C, Beccari G, Rossini FP, et al. Outcome of patients with obscure gastrointestinal bleeding after capsule endoscopy: report of 100 consecutive cases. Gastroenterology 2004;126:643-53. 24. Fireman Z, Mahajna E, Fish L, Kopelman Y, Sternberg A, Scapa E. Effect of erythromycin in gastric and small bowel transit time of video capsule endoscopy [abstract]. Gastrointest Endosc 2003;57:AB163. 25. Kim YS, Chun HJ, Kim KO, Choung RS, Jo NY, Kim YS, et al. Comparison of two bowel preparations for capsule GASTROINTESTINAL ENDOSCOPY
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26.
27.
28.
29.
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endoscopy: NPO only versus PEG [abstract]. Gastrointest Endosc 2003;57:AB169. Kim YS, Chun HJ, Kim KO, Choung RS, Jo NY, Kim YS, et al. Effect of erythromycin on the transit time of capsule endoscope through small intestine [abstract]. Gastrointest Endosc 2003;57:AB168. O’Loughlin CJ, Sable AI, Alazmi W, Barkin JS. Comparison of polyethylene glycol-electrolyte lavage (PEG-EL) preparation versus standard preparation on small bowel mucosal visualization for wireless capsule endoscopy (WCE) [abstract]. Am J Gastroenterol 2003;98:S74. Albert J, Gobel CM, Lebke J, Lotterer E, Nietsch H, Fleig WE. Simethicone for small bowel preparation for capsule endoscopy: a systematic, single-blinded, controlled study. Gastrointest Endosc 2004;59:487-91. Mergener K, Enns R, Brandabur JJ, Schembre DB, Smith M. Complications and problems with capsule endoscopy: results
30.
31.
32.
33.
from two referral centers [abstract]. Gastrointest Endosc 2003;57:AB170. Hutchinson DS, Barawi M, Bermudez F, Taggart T, Ravi V. A prospective study assessing the complication associated with the use of wireless capsule endoscopy (WCE) [abstract]. Am J Gastroenterol 2003;98:S290. Fireman Z, Mahajna E, Broide E, Shapiro M, Sternberg A, Kopelman Y, et al. Diagnosing small bowel Crohn’s disease with wireless capsule endoscopy. Gut 2003;52:390-2. Mascarenhas-Saraiva M, Lopes LM. Wireless capsule endoscopy (WCE) is useful for diagnosis and monitoring of small bowel Crohn’s disease [abstract]. Gastrointest Endosc 2003; 57:AB170. Tabibjadeh S, Zaidel O, Papadakis K, Vasiliauskas E, Kimble J, Treyzon L, et al. Utility of wireless capsule enteroscopy (WCE) versus serology in the evaluation of small bowel Crohn’s disease [abstract]. Gastrointest Endosc 2003; 57:AB171.
By the Numbers All of the previously published biostatistical articles are now available in a grouped format through a link, By the Numbers, under Features at www.mosby.com/gie.
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Background: Capsule endoscopy is proving to be superior to push enteroscopy and barium contrast radiography for evaluation of the small bowel. However, its impact on clinical outcome has not been thoroughly investigated. This study assessed changes in therapy based on capsule endoscopy findings and on the impact of such changes on patient outcomes. Methods: Forty-four consecutive capsule endoscopies in 43 patients were reviewed. Data were collected by systematic review of patient records and included indication, results of prior diagnostic tests, and capsule endoscopy findings. Specific interventions after capsule endoscopy and clinical outcome were noted. Results: The indication for capsule endoscopy was obscure GI bleeding in 40 patients, iron deficiency anemia in one, and right lower quadrant abdominal pain in two patients. Overall diagnostic yield was 42% (18/43 patients). Diagnostic findings included angiodysplasias (n = 13), intestinal ulcers (n = 2), Crohn’s disease (n = 2), and mass lesion (n = 1). As a result of the capsule endoscopy findings, a specific intervention was implemented in 12 of 18 patients with positive findings. These included endoscopy with coagulation (n = 5), laparotomy (n = 2), pharmacotherapy (n = 4), and discontinuation of medication (n = 1). At a mean follow-up of 6.7 months, the clinical outcome was considered positive in 7 of 43 patients (16%). Conclusions: Although it has a high diagnostic yield, capsule endoscopy has a positive influence on clinical outcome in a relatively small proportion of patients. Larger studies are needed that assess the influence of capsule endoscopy on clinical outcomes. (Gastrointest Endosc 2004;60:959-64.)
Capsule endoscopy (CE) is a major advance in visualization of the small intestine. Conventional modalities for examination of the small bowel, including barium contrast radiography, enteroclysis, push enteroscopy, Sonde endoscopy, and intraoperative enteroscopy, all have significant limitations.1-8 Since the introduction of CE,9 the indications for the procedure have expanded to include Crohn’s disease, celiac disease, polyposis syndromes, monitoring of patients after small-bowel transplantation, and unexplained abdominal pain, in addition to obscure GI bleeding (OGIB). Thus, the initial studies of CE focused on diagnostic yield, in which respect CE has been shown to be superior to push enteroscopy and barium contrast radiography.5,10-12 However, there are few studies that assess the impact of CE on clinical outcome, so that the true value of this novel technology is less well established. In particular, long-term patient follow-up was not included in most studies. The present study, therefore, evaluated the
Received April 27, 2004. For revision July 8, 2004. Accepted August 17, 2004. Reprint requests: Adam Slivka, MD, PhD, 200 Lothrop St., Mezzanine Level, C-Wing, Pittsburgh, PA 15213. Copyright Ó 2004 by the American Society for Gastrointestinal Endoscopy 0016-5107/$30.00 PII: S0016-5107(04)02226-6 VOLUME 60, NO. 6, 2004
influence of CE on therapy and its impact on patient outcomes. PATIENTS AND METHODS A total of 44 consecutive CEs (43 patients) performed at a single institution were evaluated retrospectively. To be eligible for CE, patients were required to have undergone an upper endoscopy, colonoscopy, and barium contrast radiography of the small bowel. Contraindications were the following: pregnancy, symptoms/signs of bowel obstruction, and an implanted pacemaker. CE was performed after an overnight fast. Ingestion of clear liquids was permitted 4 hours after swallowing the capsule. Recording of the CE was disconnected after 8 hours. The capsule images were interpreted by one of two gastroenterologists. The medical records of all patients were reviewed in a detailed, systematic fashion. The indication for CE, the duration of symptoms before CE, and the blood transfusion requirement were noted. The results of all diagnostic tests obtained before CE, including upper endoscopy, colonoscopy, push enteroscopy, contrast radiography, scintigraphy (tagged red blood cell), mesenteric angiography, and CT were noted. Specific interventions based on the CE findings were identified by scrutinizing the medical record and by contacting primary care physicians. Details of post-CE interventions, including endoscopy with endotherapy, surgery, pharmacotherapy, and discontinuation of medication, were noted. The patient and the primary care physician were contacted to assess the current medical status of the patient and to determine whether any GASTROINTESTINAL ENDOSCOPY
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Table 1. Indication of capsule endoscopy
Table 2. Diagnostic yield of capsule endoscopy
Indication for capsule endoscopy
Findings
Obscure overt GI bleeding Obscure occult GI bleeding Iron deficiency anemia Right lower quadrant pain
No. patients (%) 22 18 1 2
(51%) (42%) (2%) (5%)
clinical intervention occurred at another facility. A successful clinical outcome was defined as the following: (1) resolution of symptoms and/or (2) normalization of the blood test(s) that prompted CE. Statistical analysis was performed by using the Fisher exact test. A p value <0.05 was considered statistically significant.
RESULTS A total of 44 CE procedures were performed in 43 patients (25 men, 18 women; mean age 56 years, range 24-86 years) from December 2001 to October 2002. The indication for CE was OGIB in 40 patients (93%); iron deficiency anemia in one patient (2%); and right lower quadrant abdominal pain, with a clinical suspicion of Crohn’s disease in two patients (5%) (Table 1). OGIB was defined as bleeding of unknown origin that persists or recurs, with no source detected by conventional evaluation, including endoscopy or contrast radiography. OGIB was further subdivided into overt (melena or hematochezia) (22 patients, 51%) and occult (positive tests for fecal occult blood) (18 patients, 42%). All patients had undergone an extensive evaluation before CE: a total of 82 upper endoscopies (range 1-4), 86 colonoscopies (range 0-10), and 54 push enteroscopies (range 0-3) were performed. One patient had undergone colectomy and ileostomy for ulcerative colitis. All patients had undergone barium contrast radiography of the small bowel before CE. All of the latter studies were negative; specifically, no stricture or mass lesion was demonstrated. Among the 43 patients, additional investigations included CT of the abdomen (n = 20), tagged-red-blood-cell scintigraphy (n = 14), a scan for Meckel’s diverticulum (n = 1), and mesenteric angiography (n = 7). Median duration of complaints before CE was 8 months (range 1 week to 15 years). Of the 40 patients with OGIB, 37 had an ongoing requirement for blood transfusion (range 2-30 units). CE was performed in every patient without complication. CE was incomplete in 22 patients (50%) because the capsule did not traverse the entire length of the small intestine before termination of the study (after approximately 8 hours). In one patient, the capsule remained lodged at the gastroesophageal junction until the battery was drained; the patient remained asymptomatic. In another patient who had 960
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No. patients
Angiodysplasias Duodenum Jejunum/ileum Jejunal ulcer Ulcer at ileocolonic anastomosis Ulceration with cobblestoning and stricturing Mass lesion
6 7 1 1 2 1 18 of 43 (42%)
undergone small-bowel transplantation, the capsule remained in the stomach for the entire examination period. CE was repeated with intravenous administration of metoclopramide (5 mg) and endoscopic placement of the capsule in the duodenum and resulted in visualization of the entire small intestine. For two CEs, the length of small intestine visualized was indeterminate. The mean time for capsule transit of the small intestine in patients in whom the entire length was visualized was 313 (78) minutes. For the incomplete studies, the mean length of time during which images were captured was 466 (28) minutes. Eleven of the 44 CEs (25%) were considered to be suboptimal because of fluid and solid debris in the small intestine. However, all examinations are included in the analysis. In 8 of the 11 suboptimal examinations, the capsule did not reach the end of the small bowel (incomplete examination). The most frequent capsule diagnosis was angiodysplasia of the small intestine (n = 13). In 7 patients, the angiodysplasias were found in the jejunum or ileum; in 6, they were in the duodenum. Oozing of blood from angiodysplasias in the duodenum was seen in 5 patients and from angiodysplasias in the terminal ileum in one patient. One patient with ulceration of the jejunum was taking a nonsteroidal anti-inflammatory drug (NSAID). One patient with a history of partial ileal resection and ileocolonic anastomosis had an ulcer with a red spot on the ileal side of the anastomosis. Ulceration, cobblestoning, and stricturing in the small bowel suggestive of Crohn’s disease were found in two patients. In one of the latter, blood was oozing from an ulcer. One patient with a history of renal-cell carcinoma had a mass in the proximal small bowel. The overall diagnostic yield (Table 2) was 42% (18 patients). Outcome The impact of CE on clinical outcome is summarized in Table 3. Of the 7 patients with VOLUME 60, NO. 6, 2004
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Table 3. Interventions based on findings of capsule endoscopy and patient outcome Finding Duodenal angiodysplasia Actively oozing Not oozing Jejunal/ileal angiodysplasia Actively oozing
Not oozing
No. patients
Intervention
5
Repeat endoscopy and coagulation None
Normalization of Hb in 2 patients None
Laparotomy and intra-operative enteroscopy Hormone therapy
Normalization of Hb
1 1
3
Not oozing Jejunal ulcer Ulcer at ileocolonic anastomosis
3 1 1
1
None NSAID stopped Laparotomy, intra-operative enteroscopy and resection Treated with mesalamine None
Ulceration, cobblestoning and stricturing Ulceration, cobblestoning and stricturing Mass lesion
1
1
None
Positive outcome
Normalization of Hb in 1 patient None No further GI blood loss Normalization of Hb
Resolution of blood loss and diarrhea None None
NSAID, Non-steroidal anti-inflammatory drug.
angiodysplasias in the jejunum or ileum, only one had a lesion that was seen to be bleeding. This was an ileal angiodysplasia, and the patient underwent laparotomy, with confirmation of the CE finding by intra-operative enteroscopy and subsequent bowel resection. After an uneventful postoperative recovery, the bleeding resolved and the hematocrit normalized. Three of the 6 patients with nonactively oozing angiodysplasias were treated by hormone replacement; only one of these patients responded with normalization of the hematocrit and no further transfusion. Hormone therapy was refused by two patients and was contraindicated in one other patient. Of the 7 patients with angiodysplasias in the jejunum or the ileum, 5 had continuing blood loss and anemia. Of the 6 patients with duodenal angiodysplasia, the 5 with active bleeding (oozing) at CE underwent upper endoscopy with identification of the lesions in all cases. In two patients, use of a side-viewing duodenoscope was required for localization. The angiodysplasias were treated by multipolar electrocoagulation. However, on followup, only two patients had stabilization of the hematocrit, with no further transfusion requirement. One patient with a non-oozing angiodysplasia in the duodenum refused further endoscopy and hormone replacement therapy and remained anemic. The patient with ulceration in the jejunum discontinued NSAID use, after which there was no further evidence of GI blood loss. In the patient with an ulcer VOLUME 60, NO. 6, 2004
with a red spot at the ileocolonic anastomosis, exploratory laparotomy with intra-operative enteroscopy confirmed the findings. Active bleeding was present at surgery, and the anastomotic segment was resected. After postoperative recovery, the hematocrit normalized, and there was no further evidence of bleeding. In two patients, the CE findings were suggestive of Crohn’s disease. One was treated with a mesalamine preparation, and the GI blood loss and diarrhea resolved. The other patient declined treatment and remained anemic, with occult GI blood loss. The patient with a history of renal cancer and a mass in the small bowel died 6 weeks after CE. A specific intervention or change in management based on the CE findings was implemented in 12 patients (28%). At a mean follow-up of 6.7 months, a clinically meaningful change in outcome had occurred in 7 patients (16%). Diagnostic yield and outcome in patients with obscure overt vs. obscure occult bleeding Of the 22 patients with obscure overt bleeding, 8 (37%) had a positive finding on CE compared with 10 of 18 patients (56%) with obscure occult bleeding (p = 0.34). A positive clinical outcome was observed in 5 of 22 patients (23%) with obscure overt bleeding and two of 18 patients (11%) with obscure occult bleeding (p = 0.43). Of the patients with a positive finding on CE, a positive outcome was noted in 5 of GASTROINTESTINAL ENDOSCOPY
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8 patients with overt bleeding and two of 10 patients with occult bleeding (p = 0.14). DISCUSSION Most published studies of CE are focused on diagnostic yield, which ranges from 45% to 70%.5,10-14 This is superior to barium contrast radiography11 and push enteroscopy.5,10-12 In one study, the diagnostic yield of CE was 45% compared with 20% for contrast radiography.11 For the indication OGIB, contrast radiography had a diagnostic yield of 5% vs. 31% for CE (p < 0.05). In the study of Lewis and Swain,10 the yield of CE was 55% compared with 30% for push enteroscopy. Because there is no reference standard, the true sensitivity and specificity of CE cannot be determined. Diagnostic yield, although important, can be misleading, given the discovery of potentially non-specific findings: it is frequently difficult to differentiate a true from a false-positive finding or a true-negative from a false-negative finding.15 This is especially the case with angiodysplasias, the most common diagnostic finding at CE. It often is difficult to be certain that a small red spot on the mucosa is really an angiodysplasia; even if it is, it is also difficult to know whether it is the actual source of bleeding. Similarly, it is challenging to differentiate a small, possibly temporary mucosal break of no clinical importance from an ulcer that is clinically significant. Thus, it is more meaningful to assess the value of CE in relation to changes in management and clinical outcomes. The present retrospective study assessed the impact of CE on clinical management and patient outcome. The diagnostic yield was 42% (18 of 43 patients), the most common finding being angiodysplasias (13 of 18 patients). Based on CE findings, a specific intervention was implemented in 12 of 18 patients with a positive CE finding, and a positive clinical outcome was noted in 7 (16%). There was no statistically significant difference in diagnostic yield and outcome of CE in patients with overt vs. those with occult bleeding. Few studies have focused specifically on clinical outcome or long-term follow-up of patients undergoing CE. In the series of Lewis and Swain,10 CE led to surgical resection of a small-bowel segment in 4 patients with OGIB. Further transfusion was not required in one of these patients, but no follow-up was given for the other 3. In a study that included 20 patients, Adler et al.12 reported follow-up for 6 patients, 5 of whom had resolution of bleeding. Other studies, preliminarily reported in abstract form alone,16-22 have followed 22 to 53 patients; diagnostic yields range from 37% to 77%. In these 962
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studies, management was changed or the clinical outcome was said to be improved in 17% to 63% of cases. In a study23 of 100 patients with OGIB, CE yielded a ‘‘definite’’ positive finding in 92.3% of patients with ongoing overt bleeding, in 12.9% of those with previous overt bleeding, and in 44.2% of those with obscure occult bleeding. Bleeding resolved more frequently in patients with ongoing overt and occult bleeding compared with patients with previous overt bleeding. Outcome was reported as improved in a high proportion of patients, but, in some cases, this was not attributable to interventions based on CE findings. In addition to the relatively small number of patients, limitations of the present series include the following: failure of 50% of the examinations to visualize the entire small intestine and suboptimal visualization in 25% because of retained fluid and solid debris. Thus, significant lesions could have been missed in the terminal ileum or obscured by retained material. If these problems could have been averted, the diagnostic yield and the number of patients with improved clinical outcomes might have been higher. In 50% of the examinations, the capsule had not reached the end of the small intestine at termination of the procedure (about 8 hours). Preliminarily reported data indicate that the administration of erythromycin, which expedites gastric emptying, increases the likelihood that the entire small bowel will be visualized during transit of the capsule.24 Improved battery life with lengthening of the time available for imaging also could minimize this shortcoming. Whether a bowel preparation improves visualization of the small-bowel mucosa also is an important issue. Visualization was classified as suboptimal for 25% of the CEs in the present series because of the presence of fluid and solid debris in the small intestine. Polyethylene glycol has been administered as a bowel preparation before CE.25-27 In a preliminary report of a prospective, blinded study, O’Loughlin et al.27 noted that administration of polyethylene glycol on the day before CE significantly improved small-bowel visualization. In the study of Lewis and Swain,10 patients drank a simethicone solution before ingestion of the capsule. Albert et al.28 found that administration of simethicone reduced the presence of intraluminal bubbles and thereby significantly improved visualization. Six patients (14%) in the present series had angiodysplasias in the duodenum that were within reach with an upper endoscope or enteroscope. These lesions were missed at prior endoscopies. In the study of Costamagna et al.,11 30% of patients had lesions in the proximal small intestine, within VOLUME 60, NO. 6, 2004
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reach of an upper endoscope, that had been missed at endoscopy. No complication because of ingestion of the capsule was encountered in the present study. In one patient, the capsule lodged at the gastroesophageal junction until the battery was drained. Lodgement did not result in any untoward effect. A radiograph of the abdomen 2 days later revealed that the capsule had passed. Although few complications of CE have been reported, Mergener et al.29 encountered prolonged retention of the capsule in 7 of 197 examinations, including small-bowel obstruction in one patient. Two capsules were extracted endoscopically, and surgery was required for removal of 5. In another study, small-bowel obstruction occurred in two of 200 patients undergoing CE.30 Because the use of CE is increasing, further prospective studies of the associated complications are clearly needed. OGIB remains the leading indication for CE. Other potential indications include Crohn’s disease,31-33 celiac disease, familial polyposis syndromes, AIDS, monitoring of small-bowel transplantation patients, and unexplained abdominal pain. The rapidly expanding use of CE in patients with unexplained abdominal pain as a means of ruling out Crohn’s disease raises certain concerns. Because CE is highly sensitive for tiny mucosal breaks, it is likely to have a much higher diagnostic yield compared with contrast radiography. However, it is presently unknown whether such findings are caused by Crohn’s disease and/or whether their discovery will contribute substantially to improved patient outcomes. As demonstrated by the present study, patient outcomes are a much more relevant standard for assessment of CE than diagnostic yield. Further study of the actual clinical impact of CE is clearly needed. REFERENCES 1. Foutch PG. Angiodysplasia of the gastrointestinal tract. Am J Gastroenterol 1993;88:807-18. 2. Nolan DJ, Traill ZC. The current role of the barium examination of the small intestine. Clin Radiol 1997;52:809-20. 3. Maglinte DD, Kelvin FM, O’Connor K, Lappas JC, Chernish SM. Current status of small bowel radiography. Abdom Imaging 1996;21:247-57. 4. Batram CI. Small bowel enteroclysis: cons. Abdom Imaging 1996;21:245-6. 5. Appleyard M, Fireman Z, Glukhovsky A, Jacob H, Shreiver R, Kadirkamanathan S, et al. A randomized trial comparing wireless capsule endoscopy with push enteroscopy for the detection of small bowel lesions. Gastroenterology 2000;119:1431-8. 6. Swain P. The role of enteroscopy in clinical practice. Gastrointest Endosc Clin N Am 1999;9:135-44. 7. Seensalu R. The Sonde exam. Gastrointest Endosc Clin N Am 1999;9:37-59. VOLUME 60, NO. 6, 2004
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8. Zaman A, Sheppard B, Katon RM. Total peroral intraoperative enteroscopy for obscure GI bleeding using a dedicated push enteroscope: diagnostic yield and patient outcome. Gastrointest Endosc 1999;50:506-10. 9. Iddan G, Meron G, Glukhovsky A, Swain P. Wireless capsule endoscopy. Nature 2000;405:417. 10. Lewis BS, Swain P. Capsule endoscopy in the evaluation of patients with suspected small intestinal bleeding: results of a pilot study. Gastrointest Endosc 2002;56:349-53. 11. Costamagna G, Shah SK, Riccioni ME, Foschia F, Mutignani M, Perri V, et al. A prospective trial comparing small bowel radiographs and video capsule endoscopy for suspected small bowel disease. Gastroenterology 2002;123: 999-1005. 12. Adler DG, Knipschield M, Gostout C. A prospective comparison of capsule endoscopy and push enteroscopy in patients with GI bleeding of obscure origin. Gastrointest Endosc 2004;59:492-8. 13. Eu 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. 14. Scapa E, Jacob H, Lewkowicz S, Migdal M, Gat D, Gluckovsky A, et al. Initial experience of wireless capsule endoscopy for evaluating occult gastrointestinal bleeding and suspected small bowel pathology. Am J Gastroenterol 2002;97:2776-9. 15. Faigel DO, Fennerty MB. ‘‘Cutting the cord’’ for capsule endoscopy. Gastroenterology 2002;123:1385-8. 16. Chong A, Taylor A, Miller A, Desmond P. Clinical outcomes following capsule endoscopy (CE) examination of patients with obscure gastrointestinal bleeding (OGB) [abstract]. Gastrointest Endosc 2003;57:AB166. 17. Guda N, Molloy R, Carron D, Gleisner M, Vakil N. Does capsule endoscopy change the management of patients? [abstract]. Gastrointest Endosc 2003;57:AB167. 18. Sacher-Huvelin S, Barouk J, Rhun ML, Des Varannes SB, Galmiche JP. Wireless capsule endoscopy of the small intestine: does it really impact the management strategy? [abstract]. Gastrointest Endosc 2003;57:AB167. 19. Delvaux M, Fassler I, Gay G. Obscure digestive bleeding (ODB): validation of a diagnostic strategy integrating capsule enteroscopy (CE) as first line intestinal investigation [abstract]. Gastrointest Endosc 2003;57:AB162. 20. Chutkan R, Toubia N, Balba N. Findings and follow-up of the first 125 video capsule patients at Georgetown University Hospital [abstract]. Gastrointest Endosc 2003;57: AB85. 21. Ciorba M, Jonnalagadda S, Zuckerman G, Stone C, Prakash C. Capsule endoscopy: varied outcomes over short-term follow-up [abstract]. Gastrointest Endosc 2003;57:AB167. 22. Leighton J, Sharma V, Malikowski M, Fleischer D. Long term clinical outcomes of capsule endoscopy (CE) in patients with obscure gastrointestinal bleeding (OGIB) [abstract]. Am J Gastroenterol 2003;98:S300. 23. Pennazio M, Santucci R, Rondonotti E, Abbiati C, Beccari G, Rossini FP, et al. Outcome of patients with obscure gastrointestinal bleeding after capsule endoscopy: report of 100 consecutive cases. Gastroenterology 2004;126:643-53. 24. Fireman Z, Mahajna E, Fish L, Kopelman Y, Sternberg A, Scapa E. Effect of erythromycin in gastric and small bowel transit time of video capsule endoscopy [abstract]. Gastrointest Endosc 2003;57:AB163. 25. Kim YS, Chun HJ, Kim KO, Choung RS, Jo NY, Kim YS, et al. Comparison of two bowel preparations for capsule GASTROINTESTINAL ENDOSCOPY
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endoscopy: NPO only versus PEG [abstract]. Gastrointest Endosc 2003;57:AB169. Kim YS, Chun HJ, Kim KO, Choung RS, Jo NY, Kim YS, et al. Effect of erythromycin on the transit time of capsule endoscope through small intestine [abstract]. Gastrointest Endosc 2003;57:AB168. O’Loughlin CJ, Sable AI, Alazmi W, Barkin JS. Comparison of polyethylene glycol-electrolyte lavage (PEG-EL) preparation versus standard preparation on small bowel mucosal visualization for wireless capsule endoscopy (WCE) [abstract]. Am J Gastroenterol 2003;98:S74. Albert J, Gobel CM, Lebke J, Lotterer E, Nietsch H, Fleig WE. Simethicone for small bowel preparation for capsule endoscopy: a systematic, single-blinded, controlled study. Gastrointest Endosc 2004;59:487-91. Mergener K, Enns R, Brandabur JJ, Schembre DB, Smith M. Complications and problems with capsule endoscopy: results
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from two referral centers [abstract]. Gastrointest Endosc 2003;57:AB170. Hutchinson DS, Barawi M, Bermudez F, Taggart T, Ravi V. A prospective study assessing the complication associated with the use of wireless capsule endoscopy (WCE) [abstract]. Am J Gastroenterol 2003;98:S290. Fireman Z, Mahajna E, Broide E, Shapiro M, Sternberg A, Kopelman Y, et al. Diagnosing small bowel Crohn’s disease with wireless capsule endoscopy. Gut 2003;52:390-2. Mascarenhas-Saraiva M, Lopes LM. Wireless capsule endoscopy (WCE) is useful for diagnosis and monitoring of small bowel Crohn’s disease [abstract]. Gastrointest Endosc 2003; 57:AB170. Tabibjadeh S, Zaidel O, Papadakis K, Vasiliauskas E, Kimble J, Treyzon L, et al. Utility of wireless capsule enteroscopy (WCE) versus serology in the evaluation of small bowel Crohn’s disease [abstract]. Gastrointest Endosc 2003; 57:AB171.
By the Numbers All of the previously published biostatistical articles are now available in a grouped format through a link, By the Numbers, under Features at www.mosby.com/gie.
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