Novel biomarker profiles to improve individual diagnosis and prognosis in patients with suspected inflammatory bowel disease: protocol for the Nordic inception cohort study (NORDTREAT).

INTRODUCTION: Inflammatory bowel disease (IBD), including ulcerative colitis and Crohn's disease, can be challenging to diagnose, and treatment outcomes are difficult to predict. In the NORDTREAT cohort study, a Nordic prospective multicentre study, we aim to identify novel molecular biomarkers of diagnostic value by assessing the diagnostic test accuracy (cross-sectionally), as well as the prognostic utility when used as prognostic markers in the long-term (cohort study). In the diagnostic test accuracy study, the primary outcome is a successful diagnosis using one or more novel index tests at baseline compared with the ECCO criteria as the reference standard. The composite outcome of the prognostic utility study is 'severe IBD' within 52 weeks from inclusion, defined as one or more of the following three events: IBD-related surgery, IBD-related hospitalisation or IBD-related death. METHODS AND ANALYSIS: We aim to recruit 800 patients referred on suspicion of IBD to this longitudinal observational study, a collaboration between 11 inclusion sites in Denmark, Iceland, Norway and Sweden. Inclusion will occur from February 2022 until December 2023 with screening and baseline visits for all participants and three outcome visits at weeks 12, 26 and 52 after baseline for IBD-diagnosed patients. Biological material (blood, faeces, biopsies, urine and hair), clinical data and lifestyle information will be collected during these scheduled visits. ETHICS AND DISSEMINATION: This study will explore novel biomarkers to improve diagnostic accuracy and prediction of disease progression, thereby improving medical therapy and the quality of life for patients with IBD.The study is approved by the Ethics Committee (DK: S-20200051, v1.4, 16.10.2021; IS: VSNb2021070006/03.01, NO: 193064; SE: DNR 2021-05090) and the Danish Data Protecting Agency (20/54594). Results will be disseminated through peer-reviewed journals, patient associations and presentations at international conferences. CLINICAL TRIAL REGISTRATION NUMBER: NCT05414578; Pre-results.

Artificial Intelligence-assisted Analysis of Pan-enteric Capsule Endoscopy in Patients with Suspected Crohn's Disease: A Study on Diagnostic Performance.

BACKGROUND AND AIM: Pan-enteric capsule endoscopy [PCE] is a highly sensitive but time-consuming tool for detecting pathology. Artificial intelligence [AI] algorithms might offer a possibility to assist in the review and reduce the analysis time of PCE. This study examines the agreement between PCE assessments aided by AI technology and standard evaluations, in patients suspected of Crohn's disease [CD]. METHOD: PCEs from a prospective, blinded, multicentre study, including patients suspected of CD, were processed by the deep learning solution AXARO® [Augmented Endoscopy, Paris, France]. Based on the image output, two observers classified the patient's PCE as normal or suggestive of CD, ulcerative colitis, or cancer. The primary outcome was per-patient sensitivities and specificities for detecting CD and inflammatory bowel disease [IBD]. Complete reading of PCE served as the reference standard. RESULTS: A total of 131 patients' PCEs were analysed, with a median recording time of 303 min. The AXARO® framework reduced output to a median of 470 images [2.1%] per patient, and the pooled median review time was 3.2 min per patient. For detecting CD, the observers had a sensitivity of 96% and 92% and a specificity of 93% and 90%, respectively. For the detection of IBD, both observers had a sensitivity of 97% and had a specificity of 91% and 90%, respectively. The negative predictive value was 95% for CD and 97% for IBD. CONCLUSIONS: Using the AXARO® framework reduced the initial review time substantially while maintaining high diagnostic accuracy-suggesting its use as a rapid tool to rule out IBD in PCEs of patients suspected of Crohn's disease.

Additional information obtained from mucosal biopsies is limited after pan-enteric capsule endoscopy in patients with suspected Crohn's disease.

Background and study aims Pan-enteric capsule endoscopy (CE) is an emerging alternative to ileo-colonoscopy for diagnosing Crohn's disease (CD). However, CE does not offer the opportunity to take biopsies to support the diagnosis. This study examined the additional information obtained with mucosal biopsies and the feasibility of CE as a single diagnostic procedure. Patients and methods This retrospective study was based on a prospective, blind multicenter trial in which patients with suspected CD were examined with ileo-colonoscopy plus segmental biopsies and CE. Histopathological findings were compared to the result of CE. Results A total of 107 patients with a complete CE were included in the analysis. CE was consistent with CD in 44 patients (41.1%) and ulcerative colitis in 10 patients (9.3%). Histopathology confirmed the result of CE in 39.3% of patients and added new diagnostic information in 6.5% of patients. A CE consistent with CD was histologically confirmed in 20.5% of patients. Biopsies most often showed non-specific inflammation (61.4%). Only one patient with a normal CE had a specific histological diagnosis (microscopic colitis). Biopsies altered the diagnosis of ulcerative colitis to CD in two patients, and in two patients with a normal CE, biopsies showed CD or ulcerative colitis. In one patient with lymphoma in the terminal ileum and cecum, CE was misinterpreted as CD. Conclusions In patients with suspected CD and an evident result of CE, the additional information obtained from biopsies is limited, and CE as a single diagnostic procedure might be feasible in selected patients. Biopsies are warranted, however, in patients with an atypical endoscopic appearance or suspected malignancy.

Intestinal ultrasound in patients with suspected Crohn's disease - results of a prospective evaluation by trainees.

BACKGROUND AND AIMS: Intestinal ultrasound (IUS) performed by experts is a valuable tool for the diagnostic work-up and monitoring of Crohn's disease (CD). However, concern about insufficient training and perceived high inter-observer variability limit the adoption of IUS in CD. We examined the diagnostic accuracy of trainee-performed IUS in patients with suspected CD. METHOD: Patients recruited to a prospective trial investigating the diagnostic accuracy of magnetic resonance enterocolonography (MREC) in patients with clinically suspected CD underwent IUS performed by trainees. The primary end-point was IUS per-patient sensitivity and specificity for ileocolonic CD determined by ileocolonoscopy. RESULTS: 129 patients with clinically suspected CD and a complete IC and IUS were included in the analysis. IUS detected signs of CD in 49 cases (small bowel 31, colon 15, small bowel, and colon 3). The sensitivity and specificity for detection of ileocolonic CD by trainee performed IUS improved during the first to the second half of the study period from 57.1% (CI 34.0-78.2) to 73.1% (CI 52.2-88.4) and 76.5% (CI 58.8-89.3) to 89.7% (CI 72.6-97.8). The overall sensitivity and specificity of diagnosing CD with IUS were 65.4% (CI 50.9-78.0) and 80.5% (CI 69.9-88.7). There was no difference in diagnostic performance between IUS and MREC for the detection of CD. CONCLUSION: Trainees improved during the study, and IUS performance in disease detection corresponded to expert-evaluated MREC.Registered at ClinicalTrials.gov (NCT03134586).

Diagnostic accuracy of pan-enteric capsule endoscopy and magnetic resonance enterocolonography in suspected Crohn's disease.

BACKGROUND AND AIMS: Magnetic resonance enterocolonography (MREC) and pan-enteric capsule endoscopy (CE) offers visualization of the entire gastrointestinal tract in a single examination. We examined the diagnostic accuracy of MREC and CE in patients with suspected Crohn's disease (CD). METHOD: In a prospective, blinded, multicenter study, we included patients with clinically suspected CD. Patients were examined with MREC, CE, and ileocolonoscopy (IC) within 2 weeks. The primary outcome was per patient sensitivity, specificity, and diagnostic accuracy for ileocolonic CD. IC served as reference standard. RESULTS: 153 patients were included in the study and IC, MREC, and CE was performed in 152, 151, 133 patients, respectively. CD was diagnosed with IC in 59 (39%) patients (terminal ileum (TI) 22, colon 20, TI and colon 17). The sensitivity and specificity for diagnosing ileocolonic CD with MREC was 67.9% (CI 53.7-80.1) and 76.3% (CI 65.2-85.3) (TI 76.9% and 85.6%; colon 27% and 93%) compared to 87.5% (CI 73.2-95.8) and 87.8% (CI 78.2-94.3) with CE (TI 96.6% and 87.5%; colon 75.0% and 93.0%). The sensitivity of CE was superior to that of MREC (p = 0.02). The patient experienced discomfort was equal with CE and MREC and significantly less than with IC. CONCLUSION: In patients with suspected CD, CE has a high sensitivity for diagnosing CD in the TI and colon, which is superior to that of MREC. The sensitivity of MREC for diagnosing CD in the colon is poor. CE could be a patient-friendly alternative to IC in selected patients with suspected CD. Registered at ClinicalTrials.gov: NCT03134586.

Adherence to the bowel cleansing regimen for pan-enteric capsule endoscopy in patients with suspected Crohn's disease and factors affecting the image quality.

OBJECTIVE: Pan-enteric capsule endoscopy (CE) is an attractive diagnostic approach in patients examined for Crohn's disease (CD). The aim of this study was to examine the adherence to the recommended bowel cleansing regimen and determine clinical factors affecting the image quality. METHODS: In a prospective blinded trial, patients with suspected CD were examined with the PillCam Crohn's capsule after bowel preparation with 2 + 2 L of polyethylene glycol (PEG) and sodium phosphate booster. The image quality was graded on a four-point scale. A good or excellent image quality defined a diagnostic procedure. RESULTS: Fifty-nine patients participated. The mean volume of PEG was 2.5 L (CI 2.3-2.8). Ten patients (17%) were able to drink all 4 L of PEG, and 44 patients (75%) ingested ≥2 L. The image quality was poor, fair, good or excellent in 0%, 29.3%, 29.3% and 41.4%, respectively. The mean volume of PEG was 1.9 L (CI 1.4-2.4), 2.2 L (CI 1.8-2.7) and 3.2 L (CI 2.8-3.5) in patients with a fair, good or excellent image quality (p < .001). In a regression analysis, only the volume of PEG was associated with the obtained image quality (rs=0.52; p < .001). The diagnostic yield was equal in patients with a diagnostic or non-diagnostic procedure (43.9% and 47.1%, respectively). CONCLUSIONS: In patients examined with pan-enteric CE for suspected CD, the volume of PEG is the major factor affecting the image quality. Although few patients are able to ingest the recommended volume, the diagnostic yield is not affected.

Outcomes and Long-Term Effects of COVID-19 in Patients with Inflammatory Bowel Diseases - A Danish Prospective Population-Based Cohort Study with Individual-Level Data.

BACKGROUND AND AIMS: The health consequences of coronavirus disease 2019 [COVID-19] among patients with ulcerative colitis [UC] and Crohn's disease [CD] remain largely unknown. We aimed to investigate the outcomes and long-term effects of COVID-19 in patients with UC or CD. METHODS: We conducted a prospective, population-based study covering all Danish patients with CD or UC and confirmed COVID-19 between January 28, 2020 and April 1, 2021, through medical records and questionnaires. RESULTS: All 319 patients with UC and 197 patients with CD who developed COVID-19 in Denmark were included in this study and compared with the Danish background population with COVID-19 [N = 230 087]. A significantly higher risk of COVID-19-related hospitalization was observed among patients with UC (N = 46 [14.4%], relative risk [RR] = 2.49 [95% confidence interval, CI, 1.91-3.26]) and CD (N = 24 [12.2%], RR = 2.11 [95% CI 1.45-3.07]) as compared with the background population (N = 13 306 [5.8%]). A similar pattern was observed for admission to intensive care (UC: N = 8 [2.51%], RR = 27.88 [95% CI 13.88-56.00]; CD: N = 3 [1.52%], RR = 16.92 [95% CI 5.46-52.46]). After a median of 5.1 months (interquartile range [IQR] 4.5-7.9), 58 [42.3%] and 39 [45.9%] patients with UC and CD, respectively, reported persisting symptoms which were independently associated with discontinuation of immunosuppressive therapies during COVID-19 (odds ratio [OR] = 1.50 [95% CI 1.07-10.22], p = 0.01) and severe COVID-19 (OR = 2.76 [95% CI 1.05-3.90], p = 0.04), but not with age or presence of comorbidities. CONCLUSION: In this population-based study of 516 patients with IBD and COVID-19, 13.6% needed hospitalization and 2.1% required intensive care. Furthermore, sequelae were frequent, affecting 43.7% of COVID-19-infected patients. These findings might have implications for planning the healthcare of patients in the post-COVID-19 era.

Vedolizumab as first-line biological therapy in elderly patients and those with contraindications for anti-TNF therapy: a real-world, nationwide cohort of patients with inflammatory bowel diseases.

BACKGROUND: Data from real-life populations about vedolizumab as first-line biological therapy for ulcerative colitis (UC) and Crohn's disease (CD) are emerging. OBJECTIVE: To investigate the efficacy and safety of vedolizumab in bio-naïve patients with UC and CD. METHODS: A Danish nationwide cohort study was conducted between November 2014 and November 2019. Primary outcomes were clinical remission, steroid-free clinical remission, and sustained clinical remission from weeks 14 through 52. RESULTS: The study included 56 patients (UC:31, CD:25) who initiated treatment with vedolizumab mainly because of contraindications to anti-TNFs, of whom 54.8 and 24.0%, respectively received systemic steroids at the initiation. Rates of clinical remission at weeks 6, 14, and 52 were 32.0, 48.0, and 40.0%, respectively, in UC, and 36.8, 36.8, and 47.4% in CD. Steroid-free clinical remission at week 52 was achieved among 36.0 and 47.4% of UC and CD patients, while sustained clinical remission was achieved in 32.0 and 36.8%. Lack of remission was associated with being female (68.8 vs. 11.1%, p = .01) in UC and non-structuring, non-penetrating behavior in CD (90.0 vs. 44.4%, p = .03); however, this was not confirmed in multivariate analysis. Discontinuation due to primary non-response occurred in 20.0 and 5.3% of UC and CD patients, respectively, while rates of secondary loss of response were 12.0 and 5.3% after 52 weeks of follow-up. Vedolizumab was well-tolerated as only one UC patient experienced a serious adverse event. CONCLUSION: Vedolizumab is effective in the achievement of short-term, long-term, and steroid-free clinical remission in bio-naïve UC and CD patients.

Serological Assessment of the Quality of Wound Healing Processes in Crohn's Disease.

BACKGROUND AND AIMS: Crohn's disease (CD) is a chronic inflammatory condition characterized by continuous mucosal damage and ongoing wound healing of the intestines. The fibrinolytic system is involved in early parts of the wound healing process. Fibrin is a key mediator of primary blood clot formation and is formed by cross-linking of fibrinogen. To gain insights into the dynamics of wound healing in CD patients we investigated the conversion of fibrinogen into fibrin by the pro-peptide FPA, the amount of factor XIII cross-linked fibrin and total fibrin clot. METHODS: Serum samples of 35 CD patients, 15 non-inflammatory bowel disease (non-IBD) patients and 39 age-matched healthy controls were analyzed for three novel neo-epitope markers: D-fragment and D-dimer, reflecting the degradation of total fibrin clot and factor XIII cross-linked fibrin, as well as FPA, reflecting synthesis of fibrin. RESULTS: Crohn's disease patients had a significantly lower D-dimer level (p=0.0001) compared to healthy controls. Crohn's disease and non-IBD patients had a significantly higher level of FPA (p<0.0001) and D-fragment/D-dimer ratio (p<0.0001 and p=0.02). FPA, D-dimer and D-fragment/D-dimer ratio could distinguish CD patients from healthy controls with area under the curve of 0.92 (95% CI 0.83-0.97), 0.78 (95% CI 0.67-0.87) and 0.85 (95% CI 0.75-0.93), respectively. CONCLUSION: Wound healing parameters were clearly changed in CD patients. FPA levels were higher in CD patients as compared to healthy controls, indicating more ongoing wound healing. D-dimer levels were lower in CD patients than in healthy controls, indicating impaired wound healing due to poor quality of factor XIII cross-linked fibrin and clot resolution.

[CVID is a multifaceted disease].

Common variable immunodeficiency disease (CVID) is the most common primary immunodeficiency in adults, and multiple organs may be involved. This is a case report of a 49-year-old female patient with granulomatous-lymphocytic interstitial lung disease, liver fibrosis, portal hypertension and rectal cancer. Examinations showed non-necrotic granulomas in her lungs, mediastinal glands and liver, and she was seen in six different specialities. The multifaceted manifestation of CVID calls for multidisciplinary collaboration.

Ulcerative colitis, Crohn's disease, and irritable bowel syndrome have different profiles of extracellular matrix turnover, which also reflects disease activity in Crohn's disease.

BACKGROUND: Increased protease activity is a key pathological feature of inflammatory bowel disease (IBD). However, the differences in extracellular matrix remodelling (ECM) in Crohn's disease (CD) and ulcerative colitis (UC) are not well described. An increased understanding of the inflammatory processes may provide optimized disease monitoring and diagnostics. We investigated the tissue remodelling in IBD and IBS patients by using novel blood-based biomarkers reflecting ECM remodelling. METHODS: Five ECM biomarkers (VICM, BGM, EL-NE, C5M, Pro-C5) were measured by competitive ELISAs in serum from 72 CD patients, 60 UC patients, 22 patients with irritable bowel syndrome (IBS), and 24 healthy donors. One-way analysis of variance, Mann-Whitney U-test, logistic regression models, and receiver operator characteristics (ROC) curve analysis was carried out to evaluate the diagnostic accuracy of the biomarkers. RESULTS: The ECM remodelling was significantly different in UC compared to CD. The best biomarker combination to differentiate UC from CD and colonic CD was BGM and VICM (AUC = 0.98, P<0.001; AUC = 0.97, P<0.001), and the best biomarker combination to differentiate IBD from IBS patients were BGM, EL-NE, and Pro-C5 (AUC = 0.8, P<0.001). When correcting for the use of immunosuppressant and elevated CRP levels (CRP>5mg/mL), correlation of Pro-C5 (r = 0.36) with CDAI was slightly improved compared to CRP (r = 0.27) corrected for the use of immunosuppressant. Furthermore, BGM and EL-NE biomarkers were highly associated with colon inflammation in CD patients. CONCLUSION: ECM fragments of tissue remodelling in IBD affect UC and CD differently, and may aid in differentiating IBD from IBS (EL-NE, BGM, Pro-C5), and UC from CD patients (BGM, VICM). Formation of type V collagen is related to the level of inflammation in CD and may reflect disease activity in CD.

The Danish National Registry for Biological Therapy in Inflammatory Bowel Disease.

AIM: The aims of The Danish National Registry for Biological Therapy in Inflammatory Bowel Disease are to ensure that biological therapy and the clinical management of patients with inflammatory bowel disease (IBD) receiving biological treatment are in accordance with the national clinical guidelines and, second, the database allows register-based clinical epidemiological research. STUDY POPULATION: The study population comprises all Danish patients with IBD (both children and adults) with ulcerative colitis, Crohn's disease, and IBD unclassified who receive biological therapy. Patients will be enrolled consecutively when biological treatment is initiated. MAIN VARIABLES: The variables in the database are: diagnosis, time of diagnosis, disease manifestation, indication for biological therapy, previous biological and nonbiological therapy, date of visit, clinical indices, physician's global assessment, pregnancy and breastfeeding (women), height (children), weight, dosage (current biological agent), adverse events, surgery, endoscopic procedures, and radiology. DESCRIPTIVE DATA: Eleven clinical indicators have been selected to monitor the quality of biological treatment. For each indicator, a standard has been defined based on the available evidence. National results will be published in an annual report and local results on a quarterly basis. The indicators will be reported as department-specific proportions with 95% confidence intervals, and the national average will be provided for comparison. An estimated 1,200-1,300 new biological therapies are initiated each year in Danish patients with IBD. CONCLUSION: The database will be available for research during 2016. Data will be made available by The Danish Clinical Registries (www.rkkp.dk).

Symptomatic Patency Capsule Retention in Suspected Crohn's Disease.

The main limitation of capsule endoscopy is the risk of capsule retention. In patients with suspected Crohn's disease, however, this complication is rare, and if a small bowel stenosis is not reliably excluded, small bowel patency can be confirmed with the Pillcam patency capsule. We present two patients examined for suspected Crohn's disease who experienced significant symptoms from a retained patency capsule. Both patients had Crohn's disease located in the terminal ileum. In one patient, the patency capsule caused abdominal pain and vomiting and was visualized at magnetic resonance enterography 9 days after ingestion. Symptoms improved spontaneously. Another patient experienced small bowel perforation with severe peritonitis caused by an intact patency capsule wedged in a small bowel stricture. We conclude that the Pillcam patency capsule is an effective modality for securing small bowel patency prior to capsule endoscopy. However, it should be emphasized that delayed patency capsule degradation and symptomatic capsule retention is a rare but potentially severe complication which should be treated aggressively, either medically or endoscopically.

Fragments of Citrullinated and MMP-degraded Vimentin and MMP-degraded Type III Collagen Are Novel Serological Biomarkers to Differentiate Crohn's Disease from Ulcerative Colitis.

BACKGROUND AND AIMS: A hallmark of inflammatory bowel disease [IBD] is chronic inflammation, which leads to excessive extracellular matrix [ECM] remodelling and release of specific protein fragments, called neoepitopes. We speculated that the biomarker profile panel for ulcerative colitis [UC] and Crohn's disease [CD] represent a heterogeneous expression pattern, and may be applied as a tool to aid in the differentiation between UC and CD. METHODS: Serum biomarkers of degraded collagens I, III-IV [C1M, C3M, and C4M], collagen type 1 and IV formation [P1NP, P4NP], and citrullinated and MMP-degraded vimentin [VICM] were studied with a competitive ELISA assay system in a cohort including 164 subjects [CD n = 72, UC n = 60, and non-IBD controls n = 32] and a validation cohort of 61 subjects [CD n = 46, and UC n = 15]. Receiver operating characteristic curve analysis and logistic regression modelling were carried out to evaluate the discriminative power of the biomarkers. RESULTS: All biomarkers were corrected for confounding factors. VICM and C3M demonstrated the highest diagnostic power, alone, to differentiate CD from UC with an area under the curve [AUC] of 0.77 and 0.69, respectively. Furthermore, the biomarkers C1M [AUC = 0.81], C3M [AUC = 0.83], VICM [AUC = 0.83], and P1NP [AUC = 0.77] were best to differentiate UC from non-IBD. The best combinations of biomarkers to differentiate CD from UC and UC from non-IBD were VICM, C3M, C4M [AUC = 0.90] and VICM, C3M [AUC = 0.98] respectively. CONCLUSIONS: Specific extracellular matrix degradation markers are elevated in IBD and can discriminate CD from UC and UC from non-IBD controls with a high diagnostic accuracy.

Celiac disease: diagnosis and treatment.

This national clinical guideline approved by the Danish Society for Gastroenterology and Hepatology describes the diagnosis and treatment of celiac disease (CD) in adults. CD is a chronic immune-mediated enteropathy of the small intestine triggered by the ingestion of gluten-containing proteins, which are found in wheat, rye, and barley. The disease prevalence is 0.5-1.0%, but CD remains under-diagnosed. The diagnosis relies on the demonstration of lymphocyte infiltration, crypt hyperplasia, and villous atrophy in duodenal biopsies. Serology, malabsorption, biochemical markers, and identification of specific HLA haplotypes may contribute to CD diagnosis. Classical CD presents with diarrhoea and weight loss, but non-classical CD with vague or extraintestinal symptoms is common. The treatment for CD is a lifelong gluten-free diet (GFD), which, in the majority of patients, normalises the small intestinal mucosa and absorption. Adherence to a GFD usually requires dietary advice from a clinical dietician. The monitoring of antibody levels and malabsorption markers is crucial during follow-up and allows for early treatment of disease complications. Important complications include osteoporosis, iron and vitamin deficiencies, and enteropathy-associated T-cell lymphoma.

Colonoscopy surveillance for dysplasia and colorectal cancer in patients with inflammatory bowel disease.

The risk of colorectal cancer (CRC) and dysplasia in patients with inflammatory bowel disease (IBD) has been highly debated as risk estimates from different studies vary greatly. The present national Danish guideline on colonoscopy surveillance for dysplasia and colorectal cancer in patients with IBD is based on a thorough review of existing literature with particular focus on recent studies from Denmark revealing a lower risk of CRC than previously assumed. The overall risk of CRC in the Danish IBD population does not appear to be different from that of the background population; however, in some subgroups of patients the risk is increased. These subgroups of patients, who should be offered colonoscopy surveillance, include patients with ulcerative colitis having extensive disease and a long disease duration (10-13 years); early age at onset (less than 19 years of age) of ulcerative colitis; and patients with ulcerative colitis as well as Crohn's disease with a concomitant diagnosis of primary sclerosing cholangitis. A colonoscopy surveillance program is recommended in these subgroups with intervals ranging from every 3-6 months to every 5 years, using chromoendoscopy with targeted biopsies of the lesion and adjacent mucosa, instead of conventional colonoscopy with random biopsies. Preferably, the colonoscopy should be performed during clinical remission. If a lesion is detected the endoscopical resectability together with the pathology of the lesion and the adjacent mucosa determine how the lesion should be treated.

High sensitivity of quick view capsule endoscopy for detection of small bowel Crohn's disease.

BACKGROUND AND AIM: Capsule endoscopy (CE) has a high sensitivity for diagnosing small bowel Crohn's disease, but video analysis is time-consuming. The quick view (qv) function is an effective tool to reduce time consumption. The aim of this study was to determine the rate of missed small bowel ulcerations with qv-CE compared with standard view and the diagnostic accuracy of qv-CE in suspected Crohn's disease. METHODS: This study consisted of two parts: (i) 12 small bowel segments with Crohn's disease of varying severity were selected for a detailed analysis of the number and type of lesions visualized with CE and qv-CE, and (ii) a blinded study of the diagnostic accuracy of qv-CE including 40 patients with suspected Crohn's disease. Ileocolonoscopy and CE served as gold standard. RESULTS: Part 1: CE visualized 171 ulcerations compared with 102 detected with qv-CE (miss rate 40%, P = 0.02). Part 2: qv-CE identified 15 of 16 patients with small bowel Crohn's disease corresponding to a 94% sensitivity, and overall, 39 out of 40 patients were classified correct (diagnostic accuracy 98%). Qv-CE was false negative in one patient because of a leap of 3 min and 20 s in the terminal ileum. Reading times varied from 5 to 18 min (median 10). CONCLUSION: Despite a significant number of missed lesions, qv-CE is a safe and time-reducing method for diagnosing small bowel Crohn's disease. To avoid false negative cases, we recommend viewing the terminal ileum in standard view.

Ileoscopy reduces the need for small bowel imaging in suspected Crohn's disease.

INTRODUCTION: In suspected Crohn's disease (CD), current diagnostic guidelines recommend additional small bowel imaging irrespective of the findings at ileocolonoscopy. Magnetic resonance imaging enterography (MRE) and computed tomography enterography (CTE) are regarded first line imaging techniques and should generally precede capsule endoscopy. MATERIAL AND METHODS: This article brings together results from a prospective blinded diagnostic study of MRE, CTE, capsule endoscopy and faecal calprotectin (fCal) in 93 patients undergoing their first diagnostic work-up for CD. RESULTS: In patients with suspected CD, fCal is useful for the identification patients without need for colonoscopy or small bowel imaging. Patients with an elevated fCal should undergo colonoscopy including a persistent attempt to intubate the terminal ileum. CD isolated in the upper small bowel is rare, and in patients with a normal ileocolonoscopy or non-complicated CD in the colon and/or terminal ileum, small bowel imaging provides little extra information compared to ileoscopy alone. Small bowel imaging is primarily indicated if ileoscopy is not achieved and capsule endoscopy is recommended as first line imaging technique. If small bowel stenosis is not ruled out, a preceding test with a patency capsule can be performed to avoid capsule retention. MRE and CTE are complimentary modalities preferably used in patients with stenosis detected at ileocolonoscopy or suspicion of extra-intestinal disease complications. CONCLUSION: Our results suggest that a diagnostic approach different to that described in the guidelines may be expedient. FUNDING: not relevant. TRIAL REGISTRATION: The study was approved by the Ethics Committee of Southern Denmark (S-20070072) and the Danish Data Protection Agency (journal number: 2007-41-0675). ClinicalTrials.gov identifier: NCT01019460.

Diagnostic accuracies of MR enterography and CT enterography in symptomatic Crohn's disease.

OBJECTIVE: In patients, with symptomatic Crohn's disease (CD), valid information about the presence or absence of small bowel disease activity and stenosis is clinically important. Such information supports decisions about medical or surgical therapy and can be obtained with MR enterography (MRE) or CT enterography (CTE). MATERIALS AND METHODS: A total of 50 patients with symptomatic pre-existing CD and a demand for small bowel imaging to support changes in treatment strategy were included in this prospective and blinded study. MRE and CTE were performed on the same day in alternating order and subsequently compared with the gold standard: pre-defined lesions at ileoscopy (n = 30) or surgery with (n = 12) or without (n = 3) intra-operative enteroscopy. RESULTS: A total of 35 patients had active small bowel CD (jejunum 0, ileum 1, (neo)-terminal ileum 34) and 20 had small bowel stenosis. The sensitivity and specificity of MRE for detection of small bowel CD was 74% and 80% compared to 83% and 70% with CTE (p ≥ 0.5). MRE and CTE detected small bowel stenosis with 55% and 70% sensitivities, respectively (p = 0.3) and 92% specificities. CONCLUSIONS: MRE and CTE have comparable diagnostic accuracies for detection of small bowel CD and stenosis. In symptomatic patients with CD and high disease prevalence, positive predictive values are favorable but negative predictive values are low. Consequently, MRE and CTE can be relied upon, if a positive result is obtained whereas a negative enterography should be interpreted with caution.

Fecal calprotectin is equally sensitive in Crohn's disease affecting the small bowel and colon.

OBJECTIVE: The utility of fecal calprotectin (fCal) in small bowel Crohn's disease (CD) remains to be clarified. The primary aim of this study was to determine levels of fCal in CD restricted to the small bowel compared with CD affecting the colon, in patients undergoing their first diagnostic work-up. In addition, the study assessed the sensitivity and specificity of fCal in suspected CD. MATERIAL AND METHODS: A total of 83 patients referred to gastroenterology out-patient clinic with suspected CD were included in this prospective, blinded study, and fCal was measured during diagnostic work-up. Ileo-colonoscopy + capsule endoscopy/surgery (n = 81), ileo-colonoscopy + upper endoscopy (n = 1), and ileo-colonoscopy (n = 1) served as gold standard for the presence and location of CD. RESULTS: A total of 40 patients were diagnosed with CD: small bowel 13, colonic 16, and ileo-colonic 11. Levels of fCal were equal in patients with small bowel or colonic CD: median 890 mg/kg and 830 mg/kg, respectively (p = 1.0). With a 50 mg/kg cut-off, CD in the small intestine and colon was diagnosed with 92% and 94% sensitivities, respectively, and the overall sensitivity and specificity of fCal was 95% and 56%. In this cohort, CD was ruled out with a negative predictive value of 92%. CONCLUSIONS: This is the first study to show that fCal is equally sensitive in colonic and small bowel CD. In patients suspected of CD, fCal is an effective marker to rule out this diagnosis and select patients for endoscopy.