Diagnostic Accuracy of Capsule Endoscopy for Small Bowel Crohn's ...

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participation in the study. Small bowel stenosis detected at. MRE, CTE, and/or ileocolonoscopy contraindicated CE. Gold Standard. Ileoscopy (n. 70), ileoscopy.
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Diagnostic Accuracy of Capsule Endoscopy for Small Bowel Crohn’s Disease Is Superior to That of MR Enterography or CT Enterography MICHAEL DAM JENSEN,* TORBEN NATHAN,* SØREN RAFAEL RAFAELSEN,‡ and JENS KJELDSEN§ *Department of Internal Medicine, Section of Gastroenterology, and ‡Department of Radiology, Lillebaelt Hospital Vejle, Vejle; and §Department of Medical Gastroenterology, Odense University Hospital, Odense, Denmark

See related article, Tromm A et al, on page 425 in Gastroenterology. BACKGROUND & AIMS: Capsule endoscopy (CE) detects small bowel Crohn’s disease with greater diagnostic yield than radiologic procedures, although there are concerns that CE has low specificity. We compared the sensitivity and specificity of CE, magnetic resonance imaging enterography (MRE) and computed tomography enterography (CTE) in patients with suspected or newly diagnosed Crohn’s disease. METHODS: We performed a prospective, blinded study of 93 patients scheduled to undergo ileocolonoscopy, MRE, and CTE and subsequently CE if stenosis was excluded. Physicians reporting CE, MRE, and CTE results were blinded to patient histories and findings from ileocolonoscopy and other small bowel examinations. Results were compared with those from ileoscopy (n ⫽ 70), ileoscopy and surgery (n ⫽ 4), or surgery (n ⫽ 1). RESULTS: Twentyone patients had Crohn’s disease in the terminal ileum. The sensitivity and specificity for diagnosis of Crohn’s disease of the terminal ileum were 100% and 91% by CE, 81% and 86% by MRE, and 76% and 85% by CTE, respectively. Proximal Crohn’s disease was detected in 18 patients by using CE, compared with 2 and 6 patients by using MRE or CTE, respectively (P ⬍ .05). Small bowel stenosis was observed in 5 patients by using CTE and 1 patient by using MRE. Cross-sectional imaging results indicated additional stenoses in only 2 of the patients who received complete ileocolonoscopies. CONCLUSIONS: In suspected or newly diagnosed Crohn’s disease, MRE and CTE have comparable sensitivities and specificities. In patients without endoscopic or clinical suspicion of stenosis, CE should be the first line modality for detection of small bowel Crohn’s disease beyond the reach of the colonoscope.

radiography, CTE, and ileoscopy in patients with suspected CD.7 However, comparing diagnostic yields can be misleading because false-positive lesions contribute to a high diagnostic yield.8 A new diagnostic test should be characterized by its sensitivity and specificity on the basis of a comparison with a gold standard. By using an accepted gold standard for examination of the terminal ileum, the aim of this study was to compare the diagnostic sensitivity and specificity of CE, MRE, and CTE in patients with suspected or newly diagnosed CD.

Materials and Methods This prospective, blinded, multicenter study recruited patients from 4 centers managing adult patients with inflammatory bowel diseases (http://ClinicalTrials.gov Identifier NCT01019460). Patients were recruited during a 22-month period starting October 2007. All patients had a standardized work-up including medical history, physical examination, blood and stool samples, and ileocolonoscopy. MRE and CTE were performed on the same day at a single center. Subsequently, CE was performed in patients without stenosis at ileocolonoscopy, MRE, and CTE. The radiologists and physicians describing CE, MRE, and CTE were blinded to the findings at ileocolonoscopy and other small bowel examinations.

Criteria for Inclusion and Exclusion Patients with suspected or newly diagnosed CD were eligible for inclusion if they fulfilled the clinical, endoscopic, or histologic criteria or any combination of these: ●

Clinical criteria: diarrhea and/or abdominal pain for more than 1 month (or repeated episodes of diarrhea and/or abdominal pain) associated with 1 or more of the following findings: C-reactive protein ⬎5 mg/L, thrombocytosis, anemia, fever, weight loss, perianal abscess/fistula, or a family history of inflammatory bowel disease.



Endoscopic criteria (at least 1): ulcerations and/or stenosis in the terminal ileum, inflammation in the colon not involving the rectum, or aphthous lesions in the colon.

Keywords: Intestine; Autoimmune Disease; Clinical Trial; Radiology.

I

n recent years, capsule endoscopy (CE), magnetic resonance imaging enterography (MRE), and computed tomography enterography (CTE) have been increasingly used for diagnosing small bowel Crohn’s disease (CD). In previous studies, MR and CT enteroclysis were slightly inferior to conventional enteroclysis for detection of mucosal lesions,1,2 but additional diagnostic information was obtained in up to 58% of patients.1,3,4 CE lacks the ability to visualize extraintestinal manifestations, but the sensitivity for mucosal lesions is superior to conventional small bowel radiography.5,6 In a recent meta-analysis, the diagnostic yield of CE was significantly higher compared with small bowel

Abbreviations used in this paper: CD, Crohn’s disease; CE, capsule endoscopy; CTE, computed tomography enterography; FOV, field of view; MRE, magnetic resonance imaging enterography; TR/TE, reaction time/echo time. © 2011 by the AGA Institute 1542-3565/$36.00 doi:10.1016/j.cgh.2010.10.019

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Histologic criteria (at least 1): epithelioid cell granulomas, chronic inflammation of the colon not involving the rectum, or chronic inflammation in the lamina muscularis mucosae or deeper.

Growth of enteropathogenic bacteria in stool cultures, positive serologic markers for celiac disease, acute bowel obstruction, elevated serum creatinine, use of nonsteroidal anti-inflammatory drugs less than 4 weeks before small bowel examinations, severe claustrophobia, cardiac pacemaker, implanted magnetic foreign bodies, pregnancy, and lactation were exclusion criteria for participation in the study. Small bowel stenosis detected at MRE, CTE, and/or ileocolonoscopy contraindicated CE.

Gold Standard Ileoscopy (n ⫽ 70), ileoscopy ⫹ surgery (n ⫽ 4), and surgery (n ⫽ 1) served as the gold standard (Figure 1). Endoscopists were blinded to the results of small bowel examinations performed in the study protocol. Small bowel examinations were scheduled as close to the ileocolonoscopy as possible (median, 13 days). In 5 patients, ileocolonic resection was performed 67, 98, 150, 190, and 191 days after MRE and CTE, respectively. Surgeons recorded lesions on data sheets designed for this study.

Capsule Endoscopy Procedures CEs were performed at each participating center by using identical equipment and examination protocols. Examinations were performed with Pillcam SB (Given Imaging, Youqneam, Israel) and did not include bowel preparation or the use of prokinetic drugs. Patients were instructed to ingest liquid foods from noon and to fast from 10 PM on the day before the

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examination. Patients swallowed the capsule with half a glass of water and were allowed to drink additional liquids after 3 hours and to eat a light meal after 5 hours. CE readings were carried out with the Rapid 5 Software Platform (Given Diagnostic System), and physicians recorded lesions on data sheets designed for this study.

Magnetic Resonance Imaging Enterography and Computed Tomography Enterography Procedures Examinations were performed immediately after one another with a single oral contrast preparation consisting of 1000 mL 7.5% mannitol solution ingested gradually during 1 hour. Examinations were performed in alternating order, ie, patients were selected to a specific examination order according to their chronological participation in the study. MRE was carried out with an Intera 1.5T MR system with a 5 element Syn-body coil (Philips Medical Systems, Eindhoven, The Netherlands). Patients were examined in the supine position. The protocol contained the sequences Cor T1 (reaction time/echo time [TR/TE], 7/3.4; flip angle, 15 degrees; slice thickness, 4 mm; 208 matrix; field of view [FOV], 375), Cor T2 (B-FFE; TR/TE, 4.1/2.0 milliseconds; flip angle, 60 degrees; slice thickness, 5 mm; 224 matrix; FOV 400), Cor SPIR (TR/TE, 3000/125 milliseconds; flip angle, 90 degrees; slice thickness, 7 mm; 256 matrix; FOV 400), and axial T1W (TR/TE, 7/3.4; flip angle, 15 degrees; slice thickness, 4 mm; 208 matrix; FOV 375), with discontinuous breath-hold before and after contrast. Gadodiamid 0.1 mmol/kg (GE Healthcare, Medical Diagnostics, Oslo, Norway) was given intravenously, and hyoscinbutylbromide 20 mg (Buscopan; Boehringer Ingelheim, Basel, Switzer-

Figure 1. Flow chart showing the number of patients entering the study and completing examinations in accordance with the study protocol.

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land) was administered to reduce peristalsis during the procedure. CTE was performed with a 64-slice CT system (Somatom Sensation; Siemens, Erlangen, Germany) by using the following parameters: CARE-Dose: on, 120 kV, up to 150 mA; rotation time, 0.5 seconds; pitch, 1.5; collimation, 0.6 mm; increment 2. Contrast-enhanced CT scanning in the portal phase was performed after intravenous injection of 100 mL iomeprol (Iomeron; Bracco, Milan, Italy) 300 mg/mL by using an automatic injector OptiVantage DH (Mallinckrodt, Cincinnati, OH) at an injection rate of 4 mL/s. Patients with a body weight greater than 80 kg received 150 mL iomeprol at the same injection rate. All images were evaluated by using an Impax PACS workstation (Agfa, Mortsel, Belgium) with 2 Coronis monitors (1600 ⫻ 1200 pixels) (Megapixels Diagnostic Display System; Barco, Kortijk, Belgium). Lesions were documented on data sheets designed for this study.

Participating Physicians The ileocolonoscopy and small bowel examinations were assessed by separate specialists, and only 1 specialist was assigned to each modality. Five radiologists from the center performing MRE and CTE participated in the study. All readers had more than 10 years of experience in abdominal radiology and CT technique and 4 years of experience in MRE. CTE was introduced in the Department of Radiology with this study. CEs were assessed by 4 gastroenterologists from 2 participating centers. All readers had more than 15 years of experience in gastrointestinal endoscopy and a minimum of 50 previous CE readings.

Definitions The terminal ileum was defined as the distal 20 cm of the ileum, regardless of previous small bowel resections. An anatomical distinction between jejunum and ileum was not predefined. For ileoscopy and CE, the presence of more than 3 ulcerations (aphthous lesions or ulcers), irregular ulcers/fissures, or stenosis caused by fibrosis or inflammation was diagnostic of small bowel CD.9,10 A small bowel stenosis was defined as a luminal narrowing impassable by the endoscope. For surgery, the presence of mucosal ulcerations, bowel wall thickening, creeping fat, stenosis, and/or the presence of an abscess or fistula in conjunction with a diseased small bowel segment were diagnostic of small bowel CD. For MRE and CTE, the following findings were consistent with small bowel CD: mucosal ulcerations, bowel wall thickening, bowel wall hyperenhancement, small bowel stenosis, creeping fat, dilated vasa recta, and the presence of an abscess or fistula in conjunction to a diseased small bowel segment. The small bowel distention was rated on a 3-point scale: good (⬎75% of the small bowel sufficiently distended, score 3), sufficient (50%–75% of the small bowel sufficiently distended, score 2), or poor (⬍50% of the small bowel sufficiently distended, score 1). The image quality was rated good (diagnostic images without artifacts, score 3), sufficient (diagnostic images with artifacts, score 2), or poor (nondiagnostic images, score 1). A bowel wall of 6 mm or more measured perpendicular to the bowel surface was considered thickened. A small bowel stenosis was defined as a change in bowel caliber with dilatation of the

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proximal segment above 2.5 cm and/or a collapse of the distal segment.

Follow-up Patients not diagnosed with CD after initial examinations were assessed after 12 months, and final diagnoses were recorded. Patients with functional disorders who had been discharged from the outpatient clinic were telephone interviewed to uncover additional diagnostic procedures and diagnoses made at other institutions.

Statistical Analyses For sample size calculation, the prevalence of small bowel CD was estimated in a preceding audit of MREs per-

Table 1. Characteristics of 93 Patients Examined in the Study Protocol Gender (n) Male Female Age (y) Range Median Inclusion criteria (n)a Clinical Endoscopic Histologic Symptoms (n) Abdominal pain Diarrhea Weight loss ⬎3 kg C-reactive protein (mg/L) Range Median CDAIb Range Median Small bowel resection before inclusion (n) Disease status and location after gold standard assessment (n) Clinically suspected CD Newly diagnosed CD Colon Colon ⫹ terminal ileum Terminal ileum Lesions in 21 patients with CD located in the terminal ileum (n) CD at ileoscopy Aphthous lesions Large or irregular ulcers CD at ileoscopy ⫹ surgery during follow-up Large or irregular ulcers Wall thickening Stenosis Fistula CD at surgery during follow-up Large or irregular ulcers Wall thickening Stenosis aThree

28 65 15–74 30 83 43 14 79 75 42 1–94 5 40–371 152 0

53 40 19 13 8

17 10 7 3 3 3 2 1 1 1 1 1

patients fulfilled the endoscopic criterion but not the general criterion for CD. bCrohn’s disease activity index was calculated in 40 patients with newly diagnosed CD.

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Table 2. Sensitivity and Specificity of CE, MRE, and CTE for the Diagnosis of CD in the Terminal Ileum With Ileoscopy and/or Surgery as Gold Standard

Sensitivity (%) Specificity (%) PPV (%) NPV (%) Prevalence of CD in the terminal ileum with gold standard (n) False positive (n) False negative (n)

CE (n ⫽ 69)

MRE (n ⫽ 72)

CTE (n ⫽ 73)

100 (79–100) 91 (79–97) 76 (53–92) 100 (93–100) 16

81 (58–95) 86 (74–94) 71 (49–87) 92 (80–98) 21

76 (53–92) 85 (72–93) 67 (45–84) 90 (78–97) 21

5 0

7 4

8 5

NOTE. In patients examined with CE, MRE, and CTE, a gold standard assessment of the terminal ileum was obtained in 69, 72, and 73 patients, respectively. 95% confidence intervals are displayed in parentheses. NPV, negative predictive value; PPV, positive predictive value.

formed in the participating Department of Radiology. In 88 patients with clinically suspected CD, MRE detected small bowel CD in 25%. With an ideal sensitivity and specificity of 95% and a lower 95% confidence limit of 70%, 24 patients with and 72 patients without CD in the terminal ileum were required.11 Sensitivities and specificities were calculated from 2 ⫻ 2 contingency tables and compared for statistical significance in a clustered exact logistic regression model. Differences in diagnostic yields were tested for statistical significance in a clustered logistic regression model, and modalities were compared with linear combinations of estimators. The effects of small bowel distention and image quality on the sensitivity and specificity of MRE and CTE were estimated in a clustered logistic regression model in patients with and without small bowel CD defined by the gold standard.

Ethics The study was approved by the local ethics committee of southern Denmark (S-20070072) and the Danish Data Protection Agency (journal number: 2007– 41-0675). All patients gave informed consent before participation. Before inclusion of adolescents between 15 and 17 years of age, both parents and the patient gave informed consent.

Role of Funding Sources The study was initiated, planned, and undertaken by the investigators without funding from the companies providing capsules or radiologic equipment.

Results A total of 104 patients were included in the study (Figure 1). Eleven patients were excluded before small bowel examinations; 9 patients withdrew their consent for participation, 1 patient was admitted to the hospital and underwent acute examinations, and 1 patient was unable to complete both MRE and CTE and was excluded. Characteristics of 93 patients examined in the study protocol are shown in Table 1. On the basis of symptoms, clinical, and biochemical findings and the result of ileocolonoscopy with biopsies, 40 patients were diagnosed with CD. A total of 21 patients had macroscopic findings consistent with CD in the terminal ileum.

Sensitivity and Specificity of Capsule Endoscopy, Magnetic Resonance Imaging Enterography, and Computed Tomography Enterography The sensitivity and specificity for diagnosing CD in the terminal ileum were 100% and 91% for CE, 81% and 86% for MRE, and 76% and 85% for CTE, respectively (Table 2). The sensitivity of CE was significantly higher compared with CTE (P ⫽ .03), and there was a trend toward higher sensitivity compared with MRE (P ⫽ .1). Specificities were comparable (P ⬎ .5). All examinations had negative predictive values above 90%. Positive predictive values of CE, MRE, and CTE were 76%, 71%, and 67%, respectively.

Diagnostic Yield of Capsule Endoscopy, Magnetic Resonance Imaging Enterography, and Computed Tomography Enterography In 80 patients examined with all 3 examinations, the diagnostic yield was 30%, 28%, and 33%, respectively (nonsignificant in all combinations; Table 3). CD proximal to the terminal ileum was detected in 18 patients with CE compared with only 2 and 6 patients with MRE and CTE, respectively (P ⬍ .05 in comparisons to CE). In 2 patients, MRE and CTE detected enteroenteric fistulas in connection with the terminal ileum. Both modalities missed a fistula from the terminal ileum to the bladder detected at surgery.

Table 3. Number of Diagnostic CEs, MREs, and CTEs in 80 Patients Examined With all Modalities (Diagnostic Yield)

Small bowel CD Jejunum Ileum Terminal ileum CD proximal to the terminal ileum

CE

MRE

CTE

24 (30%) 9 16 24 18

22 (28%) 2 0 20 2

26 (33%) 4 2 20 6

NOTE. The same patient might have diagnostic lesions in more than 1 small bowel segment.

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Detection of Stenosis The gold standard detected stenosis in the terminal ileum in 3 patients. None of these was demonstrated with MRE, whereas CTE detected stenosis in all 3 patients. In 1 patient, CTE detected CD and stenosis in the jejunum, which was subsequently confirmed at upper endoscopy. In another patient, CTE detected a stenosis in the ileum, and ileoscopy showed CD in the terminal ileum but no stenosis. In 1 patient, MRE detected a stenosis with prestenotic dilatation in the terminal ileum. This patient had CD in the terminal ileum but no stenosis at ileoscopy (⬎20 cm of small bowel examined). There were no cases of capsule retention.

Follow-up A total of 37 patients with initial examinations not diagnostic of CD received the following diagnoses after 12month follow-up: irritable bowel syndrome (n ⫽ 31), inflammatory bowel disease unclassified (n ⫽ 4), suspected celiac disease (n ⫽ 1), and acute appendicitis (n ⫽ 1).

Quality of Magnetic Resonance Imaging Enterography and Computed Tomography Enterography MRE and CTE were the first examinations in 39 and 54 patients, respectively, and the median time interval between procedures was 36 minutes (range, 12–145 minutes). The mean volume of contrast ingested was 886 mL in patients having MRE as first examination and 932 mL in patients first examined with CTE (P ⫽ .5). The mean image quality score was 2.2 for MRE and 2.8 for CTE (P ⬍ .001), and the mean distention score was 2.2 for MRE and 2.5 for CTE (P ⬍ .001). There was no effect of bowel distention and image quality on the diagnostic sensitivity and specificity of MRE and CTE (P ⬎ .1 for all calculations).

Discussion Still today, CD is a syndrome diagnosis based on the clinical presentation and findings at endoscopy, histology, and small bowel radiology.12 For assessing the small intestine, small bowel follow-through and enteroclysis are challenged by new cross-sectional imaging modalities and endoscopic methods and are no longer generally accepted as gold standards.10,12 Studies evaluating and comparing new modalities are needed to establish the optimal diagnostic strategies in patient subgroups. In the present study, ileoscopy served as an objective gold standard with a predetermined diagnostic criterion.10 Choosing an endoscopic gold standard might favor CE because both modalities evaluate the mucosa. On the contrary, MRE and CTE primarily evaluate inflammation in the intestinal wall.13 However, CD is regarded as an inflammatory disorder arising in the intestinal mucosa,14 and aphthous lesions are considered the earliest manifestations of CD.15 In this regard, we consider an endoscopic gold standard appropriate for the initial diagnosis of CD. In this setting, CE had a sensitivity of 100% for detection of CD in the terminal ileum, compared with 81% and 76% for MRE and CTE, respectively. In 4 patients with false-negative cross-sectional imaging, lesions were superficial or scarce, but 1 patient presented with multiple irregular ulcerations at ileos-

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copy not detected with CT. Furthermore, in 11 proximal segments classified as normal with MRE and CTE, CE detected irregular ulcerations or fissures. Hence, lesions missed by MRE and CTE were primarily superficial but proximal to the terminal ileum; also more severe lesions were also missed. In 2 patients with a false-positive CE, irregular ulcerations were detected. Both patients responded to prednisolone therapy, and a clinical diagnosis of CD was made. Hence, the specificity of CE is high, and false-positive examinations are of minor significance. Specificities of MRE and CTE were 86% and 85%, respectively, corresponding to 7 and 8 false-positive examinations. In 6 MRE and 7 CTE patients, false-positive lesions were described as mild and solely located in the terminal ileum (Supplementary material). At the time of diagnosis, approximately 25% of patients have stricturing or penetrating disease,16 and performing CE as the initial small bowel examination is limited by the risk of capsule retention. Preceding small bowel radiography reduces the risk to approximately 1%.17 In the present study, CE was contraindicated in 6 of 93 patients (6%). However, in patients with a complete ileocolonoscopy, cross-sectional imaging rarely detected additional proximal stenoses, and it should be emphasized that not all strictures on imaging translate to a mechanically significant obstruction. These results suggest the use of CE as first-line modality for detection of small bowel CD beyond the reach of the colonoscope. In selected patients with clinical suspicion of small bowel stenosis, a preceding test with a patency capsule could be helpful.10 Diagnosing small bowel CD and strictures with MRE and CTE technique is dependent on sufficient bowel distention.18,19 Poorly distended bowel loops can mask CD but also mimic inflammation because of bowel wall thickening and mural hyperenhancement in collapsed bowel segments.20 In the present study, bowel distention and image quality were rated significantly better with CTE, but analyses showed no effect of bowel distention on the diagnostic performance of MRE and CTE. In 3 patients with stenosis in the terminal ileum missed by MRE, intervals between examinations were 23, 29, and 50 minutes, respectively, and bowel distention at MRE was rated good in 1 patient and sufficient in 2. Hence, poor bowel distention or long time intervals between MRE and CTE do not explain why MRE failed to detect small bowel stenosis in these patients.

Limitations Data on the sensitivity and specificity only apply to the terminal ileum, and the performance characteristics are not necessarily valid in the proximal small bowel. Ileocolonoscopies were performed by experienced gastroenterologists at each participating center. Diagnostic criteria were used to ensure a uniform classification, but variations between multiple observers were not accounted for in this study. Separate interobserver studies for MRE/CTE and CE in patients with suspected and known CD have been carried out13,21; the interobserver agreement for detection of small bowel CD was substantial with CTE (␬ ⫽ 0.64), moderate with MRE (␬ ⫽ 0.48), and substantial with CE (␬ ⫽ 0.68). In the present study, we did not apply consensus decisions between 2 specialists for each small bowel modality, and it is unknown whether this would have impacted the calculated sensitivities and specificities.

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The minimum requirement of more than 3 aphthous lesions for the diagnosis of small bowel CD at ileoscopy and CE was proposed by Mow et al9 and adopted in subsequent studies. However, it should be emphasized that this criterion has not been prospectively validated,10 and the chosen diagnostic threshold impacts the diagnostic sensitivity and specificity. In conclusion, compared with MRE and CTE, CE had superior sensitivity for detection of CD in the terminal ileum and higher diagnostic yield in the proximal small bowel. MRE and CTE showed comparable performances, but stenoses were detected more accurately with CTE. However, in patients with a successful ileoscopy, cross-sectional imaging rarely detected additional stenoses. In patients with suspected or newly diagnosed CD without endoscopic or clinical suspicion of stenosis, CE could be the new gold standard and first-line modality for detection of small bowel CD beyond the reach of the colonoscope.

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11.

12.

13.

14. 15. 16.

Supplementary Material Note: To access the supplementary material accompanying this article, visit the online version of Clinical Gastroenterology and Hepatology at www.cghjournal.org, and at doi:10.1016/ j.cgh.2010.10.019. References 1. Masselli G, Casciani E, Polettini E, et al. Comparison of MR enteroclysis with MR enterography and conventional enteroclysis in patients with Crohn’s disease. Eur Radiol 2008;18:438 – 447. 2. Gourtsoyiannis NC, Grammatikakis J, Papamastorakis G, et al. Imaging of small intestinal Crohn’s disease: comparison between MR enteroclysis and conventional enteroclysis. Eur Radiol 2006; 16:1915–1925. 3. Schreyer AG, Geissler A, Albrich H, et al. Abdominal MRI after enteroclysis or with oral contrast in patients with suspected or proven Crohn’s disease. Clin Gastroenterol Hepatol 2004;2: 491– 497. 4. Bruining DH, Siddiki HA, Fletcher JG, et al. Prevalence of penetrating disease and extraintestinal manifestations of Crohn’s disease detected with CT enterography. Inflamm Bowel Dis 2008; 14:1701–1706. 5. Marmo R, Rotondano G, Piscopo R, et al. Capsule endoscopy versus enteroclysis in the detection of small-bowel involvement in Crohn’s disease: a prospective trial. Clin Gastroenterol Hepatol 2005;3:772–776. 6. Dubcenco E, Jeejeebhoy KN, Petroniene R, et al. Capsule endoscopy findings in patients with established and suspected smallbowel Crohn’s disease: correlation with radiologic, endoscopic, and histologic findings. Gastrointest Endosc 2005;62:538 –544. 7. Dionisio PM, Gurudu SR, Leighton JA, et al. Capsule endoscopy has a significantly higher diagnostic yield in patients with suspected and established small-bowel Crohn’s disease: a metaanalysis. Am J Gastroenterol 2009;105:1240 –1248; quiz 1249. 8. Wolf AT. Capsule endoscopy in Crohn’s disease: is seeing believing? Inflamm Bowel Dis 2007;13:1180 –1181. 9. Mow WS, Lo SK, Targan SR, et al. Initial experience with wireless capsule enteroscopy in the diagnosis and management of inflammatory bowel disease. Clin Gastroenterol Hepatol 2004;2:31– 40. 10. Bourreille A, Ignjatovic A, Aabakken L, et al. Role of small-

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bowel endoscopy in the management of patients with inflammatory bowel disease: an international OMED-ECCO consensus. Endoscopy 2009;41:618 – 637. Flahault A, Cadilhac M, Thomas G. Sample size calculation should be performed for design accuracy in diagnostic test studies. J Clin Epidemiol 2005;58:859 – 862. Van Assche G, Dignass A, Panes J, et al. The second European evidence-based consensus on the diagnosis and management of Crohn’s disease: definitions and diagnosis. Journal of Crohn’s and Colitis 2010;4:7–27. Jensen MD, Ormstrup T, Vagn-Hansen C, et al. Interobserver and intermodality agreement for detection of small bowel Crohn’s disease with MR enterography and CT enterography. Inflamm Bowel Dis 2010 Nov 15. [Epub ahead of print]. Abraham C, Cho JH. Inflammatory bowel disease. N Engl J Med 2009;361:2066 –2078. Satsangi J, Sutherland LR. Inflammatory bowel diseases. New York: Churchill Livingstone, 2003. Louis E, Collard A, Oger AF, et al. Behaviour of Crohn’s disease according to the Vienna classification: changing pattern over the course of the disease. Gut 2001;49:777–782. Cave D, Legnani P, De FR, et al. ICCE consensus for capsule retention. Endoscopy 2005;37:1065–1067. Sinha R, Murphy P, Hawker P, et al. Role of MRI in Crohn’s disease. Clin Radiol 2009;64:341–352. Hara AK, Swartz PG. CT enterography of Crohn’s disease. Abdom Imaging 2009;34:289 –295. Booya F, Fletcher JG, Huprich JE, et al. Active Crohn disease: CT findings and interobserver agreement for enteric phase CT enterography. Radiology 2006;241:787–795. Jensen MD, Nathan T, Kjeldsen J. Inter-observer agreement for detection of small bowel Crohn’s disease with capsule endoscopy. Scand J Gastroenterol 2010;45:878 – 884.

Reprint requests Address requests for reprints to: Michael Dam Jensen, MD, Department of Internal Medicine, Section of Gastroenterology, Lillebaelt Hospital Vejle, Kabbeltoft 25, DK-7100 Vejle, Denmark. e-mail: [email protected]; fax: 45-7940-6887. Acknowledgments Many thanks to the following colleagues for participation in this study: Troels Havelund, PhD, Dr Benedicte Wilson, Jane Møller Hansen, PhD, Dr Laurits Laursen, Dr Finn Møller Pedersen, Professor Ove B. Schaffalitzky de Muckadell, DMSci, and Karsten Lauritsen, DMSci, Department of Medical Gastroenterology, Odense University Hospital, Denmark; Dr Anette Hygum Knudsen, Dr Ejler Ejlersen, Bent Nyboe Andersen, DMSci, and Henrik Hey, DMSci, Department of Internal Medicine, Section of Gastroenterology, Lillebaelt Hospital Vejle, Denmark; Torben Knudsen, PhD, DMSci, Dr Thøger Thøgersen, and Dr Ulrich-Martin Bich, Department of Internal Medicine, Hospital of South West Denmark, Denmark; Claus Aalykke, PhD, and Axel MalchowMøller, DMSci, Department of Internal Medicine, Hospital of Funen Svendborg, Denmark; Dr Tina Elisabeth Ormstrup, Dr Chris VagnHansen, Dr Lone Østergaard, Dr Torben Sørensen, and charge nurse Else Ipsen, Department of Radiology, Lillebaelt Hospital Vejle, Denmark. Conflicts of interest The authors disclose no conflicts.

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Supplementary Figure 1. (A) Coronal T2W MRE image with bowel wall enhancement and enlarged lymph nodes in the mesentery; (B) coronal CTE image with bowel wall thickening and bowel wall enhancement; (C) CE with more than 3 lesions interpreted as aphthous lesions in the terminal ileum.

Side effects to the enteral and intravenous contrast contributed to the physical discomfort at MRE and CTE. The tight space inside the MR scanner caused discomfort in some patients and increased psychological discomfort with this modality.

Supplementary Material Physical and Psychological Discomfort Patients marked visual analogue scales for physical and psychological discomfort immediately after each small bowel examination. All scales were 10 cm long; 0 cm equaled no discomfort and 10 cm the worst imaginable discomfort. A total of 79 patients filled out visual analogue scales for all 3 small bowel examinations. The mean score for physical discomfort was significantly higher for MRE and CTE compared with CE (P ⬍ .001), and the mean score for psychological discomfort was significantly higher for MRE compared with CTE and CE (P ⬍ .01) (Supplementary Table 1). Supplementary Table 1.

Physical discomfort Psychological discomfort

CE

MRE

CTE

1.0 (0.6–1.4) 0.8 (0.4–1.2)

3.6 (2.9–4.4) 2.0 (1.4–2.6)

3.0 (2.3–3.6) 0.9 (0.5–1.4)

NOTE. 95% confidence intervals are displayed in parentheses.

False-Positive Small Bowel Examinations Supplementary Figure 1 A–C is from a patient with a normal ileocolonoscopy and histology from the colon and terminal ileum. After 6 months of follow-up, the patient was free of symptoms, and a diagnosis of irritable bowel syndrome was made.