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      Diagnostic accuracy of magnetic resonance enterography and small bowel ultrasound for the extent and activity of newly diagnosed and relapsed Crohn's disease (METRIC): a multicentre trial

      research-article
      , Prof, FRCR a , * , , DPhil b , , FRCR a , , MSc c , , FRCP d , , FRCR c , , PhD e , , Prof, FRCP f , , FRCR g , , BA Hons h , , FRCP d , , PhD i , , PhD j , , FRCR a , , FRCP k , , FRCR a , , MSc b , , FRCPath l , , MSc m , , FRCR n , , FRCR o , , Prof, DPhil p , , FRCS q , , FRCR r , , FRCR s , , Prof, FMedSci a , METRIC study investigators
      The Lancet. Gastroenterology & Hepatology
      Elsevier B.V

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          Summary

          Background

          Magnetic resonance enterography (MRE) and ultrasound are used to image Crohn's disease, but their comparative accuracy for assessing disease extent and activity is not known with certainty. Therefore, we did a multicentre trial to address this issue.

          Methods

          We recruited patients from eight UK hospitals. Eligible patients were 16 years or older, with newly diagnosed Crohn's disease or with established disease and suspected relapse. Consecutive patients had MRE and ultrasound in addition to standard investigations. Discrepancy between MRE and ultrasound for the presence of small bowel disease triggered an additional investigation, if not already available. The primary outcome was difference in per-patient sensitivity for small bowel disease extent (correct identification and segmental localisation) against a construct reference standard (panel diagnosis). This trial is registered with the International Standard Randomised Controlled Trial, number ISRCTN03982913, and has been completed.

          Findings

          284 patients completed the trial (133 in the newly diagnosed group, 151 in the relapse group). Based on the reference standard, 233 (82%) patients had small bowel Crohn's disease. The sensitivity of MRE for small bowel disease extent (80% [95% CI 72–86]) and presence (97% [91–99]) were significantly greater than that of ultrasound (70% [62–78] for disease extent, 92% [84–96] for disease presence); a 10% (95% CI 1–18; p=0·027) difference for extent, and 5% (1–9; p=0·025) difference for presence. The specificity of MRE for small bowel disease extent (95% [85–98]) was significantly greater than that of ultrasound (81% [64–91]); a difference of 14% (1–27; p=0·039). The specificity for small bowel disease presence was 96% (95% CI 86–99) with MRE and 84% (65–94) with ultrasound (difference 12% [0–25]; p=0·054). There were no serious adverse events.

          Interpretation

          Both MRE and ultrasound have high sensitivity for detecting small bowel disease presence and both are valid first-line investigations, and viable alternatives to ileocolonoscopy. However, in a national health service setting, MRE is generally the preferred radiological investigation when available because its sensitivity and specificity exceed ultrasound significantly.

          Funding

          National Institute of Health and Research Health Technology Assessment.

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          Most cited references27

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          The PRECIS-2 tool: designing trials that are fit for purpose.

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            Behaviour of Crohn's disease according to the Vienna classification: changing pattern over the course of the disease.

            Crohn's disease is a heterogeneous disorder with both a genetic and environmental aetiology. Clinical classifications of the disease, such as the newly proposed Vienna classification, may help to define subgroups of patients suitable for studying the influence of specific genetic or environmental factors. To assess the stability over the course of the disease of its location and behaviour, as determined according to the Vienna classification. The notes of 297 Crohn's disease patients regularly followed up at our institution were carefully reviewed retrospectively. The behaviour and location of the disease according to the Vienna classification were determined at diagnosis and after 1, 3, 5, 10, 15, 20, and 25 years of follow up. The proportions of the different behaviours and locations of the disease were calculated at these time points. A statistical analysis of the evolution of these characteristics over 10 years was performed on a subgroup of 125 patients with at least 10 years of follow up. The influence of age at diagnosis on location and behaviour of the disease was assessed as well as the influence of location on the behaviour of the disease. The location of the disease remained relatively stable over the course of the disease. Although the proportion of patients who had a change in disease location became statistically significant after five years (p=0.01), over 10 years only 15.9% of patients had a change in location (p<0.001). We observed a more rapid and prominent change in disease behaviour, which was already statistically significant after one year (p=0.04). Over 10 years, 45.9% of patients had a change in disease behaviour (p<0.0001). The most prominent change was from non-stricturing non-penetrating disease to either stricturing (27.1%; p<0.0001) or penetrating (29.4%; p<0.0001) disease. Age at diagnosis had no influence on either location or behaviour of disease. Ileal Crohn's disease was more often stricturing, and colonic or ileocolonic Crohn's disease was more often penetrating: this was already the case at diagnosis and became more prominent after 10 years (p<0.05). Location of Crohn's disease, as defined by the Vienna classification, is a relatively stable phenotype which seems suitable for phenotype-genotype analyses. Behaviour of Crohn's disease according to the Vienna classification varies dramatically over the course of the disease and cannot be used in phenotype-genotype analyses. The potential influence of genes on the behaviour of Crohn's disease should be studied in subgroups of patients defined by their disease behaviour after a fixed duration of disease.
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              A meta-analysis of the yield of capsule endoscopy compared to other diagnostic modalities in patients with non-stricturing small bowel Crohn's disease.

              Capsule endoscopy (CE) allows for direct evaluation of the small bowel mucosa in patients with Crohn's disease (CD). A number of studies have revealed significantly improved yield for CE over other modalities for the diagnosis of CD, but as sample sizes have been small, the true degree of benefit is uncertain. Additionally, it is not clear whether patients with a suspected initial presentation of CD and those with suspected recurrent disease are equally likely to benefit from CE. The aim of this study was to evaluate the yield of CE compared with other modalities in symptomatic patients with suspected or established CD using meta-analysis. We performed a recursive literature search of prospective studies comparing the yield of CE to other modalities in patients with suspected or established CD. Data on yield among various modalities were extracted, pooled, and analyzed. Incremental yield (IY) (yield of CE--yield of comparative modality) and 95% confidence intervals (95% CI) of CE over comparative modalities were calculated. Subanalyses of patients with a suspected initial presentation of CD and those with suspected recurrent disease were also performed. Nine studies (n = 250) compared the yield of CE with small bowel barium radiography for the diagnosis of CD. The yield for CE versus barium radiography for all patients was 63% and 23%, respectively (IY = 40%, p < 0.001, 95% CI = 28-51%). Four trials compared the yield of CE to colonoscopy with ileoscopy (n = 114). The yield for CE versus ileoscopy for all patients was 61% and 46%, respectively (IY = 15%, p= 0.02, 95% CI = 2-27%). Three studies compared the yield of CE to computed tomography (CT) enterography/CT enteroclysis (n = 93). The yield for CE versus CT for all patients was 69% and 30%, respectively (IY = 38%, p= 0.001, 95% CI = 15-60%). Two trials compared CE to push enteroscopy (IY = 38%, p < 0.001, 95% CI = 26-50%) and one trial compared CE to small bowel magnetic resonance imaging (MRI) (IY = 22%, p= 0.16, 95% CI =-9% to 53%). Subanalysis of patients with a suspected initial presentation of CD showed no statistically significant difference between the yield of CE and barium radiography (p= 0.09), colonoscopy with ileoscopy (p= 0.48), CT enterography (p= 0.07), or push enteroscopy (p= 0.51). Subanalysis of patients with established CD with suspected small bowel recurrence revealed a statistically significant difference in yield in favor of CE compared with all other modalities (barium radiography (p < 0.001), colonoscopy with ileoscopy (p= 0.002), CT enterography (p < 0.001), and push enteroscopy (p < 0.001)). In study populations, CE is superior to all other modalities for diagnosing non-stricturing small bowel CD, with a number needed to test (NNT) of 3 to yield one additional diagnosis of CD over small bowel barium radiography and NNT = 7 over colonoscopy with ileoscopy. These results are due to a highly significant IY with CE over all other modalities in patients with established non-stricturing CD being evaluated for a small bowel recurrence. While there was no significant difference seen between CE and alternate modalities for diagnosing small bowel CD in patients with a suspected initial presentation of CD, the trend toward significance for a number of modalities suggests the possibility of a type II error. Larger studies are needed to better establish the role of CE for diagnosing small bowel CD in patients with a suspected initial presentation of CD.
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                Author and article information

                Contributors
                Journal
                Lancet Gastroenterol Hepatol
                Lancet Gastroenterol Hepatol
                The Lancet. Gastroenterology & Hepatology
                Elsevier B.V
                2468-1253
                18 June 2018
                August 2018
                18 June 2018
                : 3
                : 8
                : 548-558
                Affiliations
                [a ]Centre for Medical Imaging, University College London (UCL), London, UK
                [b ]Institute of Applied Health Research, National Institute of Health and Research Birmingham Biomedical Research Centre, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK
                [c ]Intestinal Imaging Centre, St Mark's Hospital, London North West University Healthcare (LNWUH) National Health Service (NHS) Trust, Harrow, UK
                [d ]Department of Gastroenterology, University College Hospital, London, UK
                [e ]Department of Gastroenterology, St James's University Hospital, Leeds Teaching Hospitals NHS Trust, Leeds, UK
                [f ]Inflammatory Bowel Disease Unit, St Mark's Hospital, LNWUH NHS Trust, Harrow, UK
                [g ]Department of Radiology, Portsmouth Hospitals NHS Trust, Portsmouth, UK
                [h ]Centre for Medical Imaging, UCL, London, UK
                [i ]Department of Psychological Sciences, Birkbeck University of London, London, UK
                [j ]Department of Gastroenterology and Endoscopy, Royal Free London NHS Foundation Trust, London, UK
                [k ]Department of Gastroenterology, St George's Hospital, London, UK
                [l ]Department of Histopathology, University College Hospital, London, UK
                [m ]Comprehensive Clinical Trials Unit at UCL, Institute of Clinical Trials and Methodology, Holborn, London, UK
                [n ]Department of Radiology, Oxford University Hospitals NHS Trust, Oxford, UK
                [o ]Department of Radiology, St James's University Hospital, Leeds Teaching Hospitals NHS Trust, Leeds, UK
                [p ]Translational Gastroenterology Unit, Oxford University Hospitals, Oxford, UK
                [q ]Department of Surgery, University College Hospital, London, UK
                [r ]Department of Radiology, Royal Free London NHS Foundation Trust, London, UK
                [s ]Department of Radiology, Ninewells Hospital, Dundee, UK
                Author notes
                [* ]Correspondence to: Prof Stuart A Taylor, Centre for Medical Imaging, UCL, London W1W 7TS, UK stuart.taylor1@ 123456nhs.net
                [†]

                Investigators listed in the appendix

                Article
                S2468-1253(18)30161-4
                10.1016/S2468-1253(18)30161-4
                6278907
                29914843
                ce30866d-28bd-405a-bded-bf74342ea43c
                © 2018 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license

                This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

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