Torben Nathan

Diagnostic Accuracy of Capsule Endoscopy for Small Bowel Crohn's Disease Is Superior to That of MR Enterography or CT Enterography.

BACKGROUND & AIMS Capsule endoscopy (CE) detects small bowel Crohns 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 Crohns 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 Twenty-one patients had Crohns disease in the terminal ileum. The sensitivity and specificity for diagnosis of Crohns disease of the terminal ileum were 100% and 91% by CE, 81% and 86% by MRE, and 76% and 85% by CTE, respectively. Proximal Crohns 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 Crohns 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 Crohns disease beyond the reach of the colonoscope.

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

Abstract Objective. The utility of fecal calprotectin (fCal) in small bowel Crohns 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.

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

Abstract Objective. In patients, with symptomatic Crohns 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.

Budesonide Is More Effective Than Mesalamine or Placebo in Short-term Treatment of Collagenous Colitis

BACKGROUND & AIMS Studies reporting that budesonide is effective for the treatment of collagenous colitis have been small and differed in efficacy measures. Mesalamine has been proposed as a treatment option for collagenous colitis, although its efficacy has never been investigated in placebo-controlled trials. We performed a phase 3, placebo-controlled, multicenter study to evaluate budesonide and mesalamine as short-term treatments for collagenous colitis. METHODS Patients with active collagenous colitis were randomly assigned to groups given pH-modified release oral budesonide capsules (9 mg budesonide once daily, Budenofalk, n = 30), mesalamine granules (3 g mesalamine once daily, Salofalk, n = 25), or placebo for 8 weeks (n = 37) in a double-blind, double-dummy fashion. The study was conducted in 31 centers (hospital clinics and private practices) in Germany, Denmark, Lithuania, Spain, and the United Kingdom. The primary end point was clinical remission at 8 weeks defined as ≤ 3 stools per day. Secondary end points included clinical remission at 8 weeks, according to the Hjortswang-Criteria of disease activity, taking stool consistency into account. RESULTS A greater percentage of patients in the budesonide group were in clinical remission at week 8 than the placebo group (intention-to-treat analysis, 80.0% vs 59.5%; P = .072; per-protocol analysis, 84.8% vs 60.6%; P = .046). Based on the Hjortswang-Criteria, 80.0% of patients given budesonide achieved clinical remission compared with 37.8% of patients given placebo (P = .0006); 44.0% of patients given mesalamine achieved clinical remission, but budesonide was superior to mesalamine (P = .0035). Budesonide significantly improved stool consistency and mucosal histology, and alleviated abdominal pain. The rate of adverse events did not differ among groups. CONCLUSIONS Oral budesonide (9 mg once daily) is effective and safe for short-term treatment of collagenous colitis. Short-term treatment with oral mesalamine (3 g once daily) appears to be ineffective. ClinicalTrials.gov number, NCT00450086.

Inter-observer agreement for detection of small bowel Crohn's disease with capsule endoscopy

Abstract Objective. Compared to other modalities, capsule endoscopy (CE) has a high diagnostic yield for diagnosing small bowel Crohns disease (CD). The aim of this study was to determine the inter-observer agreement for detection of small bowel CD with predefined diagnostic criteria. Material and methods. Thirty patients with suspected or known CD were included in the study. Observers were blind to patient histories, the results of ileo-colonoscopies, and small bowel examinations. More than three ulcerations (aphthous lesions or ulcers) or the presence of stenosis caused by inflammation or fibrosis was diagnostic of small bowel CD. Three observers with experience in gastrointestinal endoscopy and CE participated in the study. Results. The presence or absence of small bowel CD was determined with complete agreement in 23 patients, nine patients with and 14 without small bowel CD. The inter-observer agreement was substantial for the diagnosis (κ = 0.68) and moderate for the localization of CD (κ = 0.44). Aphthous lesions were detected with only fair agreement (κ = 0.38). The time intervals to passage of the pylorus and ileo-caecal valve were detected with excellent intra-class correlation. Conclusions. CE is performed with substantial inter-observer agreement for detection of small bowel CD. In the majority of patients, the presence or absence of small bowel CD is unequivocal. However, in patients with few or minor lesions, the diagnosis is observer dependent.

Histiocytic disorders of the gastrointestinal tract

The morphologic diagnosis of histiocytic lesions of the gastrointestinal tract can be challenging, and several disorders have to be considered in their differential diagnosis. We present one of the most widespread examples of xanthomatosis of the gastrointestinal tract published so far and give a short review on histiocytic disorders of the gastrointestinal tract in general. The primary histiocytic disorders of uncertain origin, Rosai-Dorfman disease, Langerhans cell histiocytosis, and Erdheim-Chester disease, are addressed. Reactive and infectious conditions such as xanthomatosis, xanthogranulomatous inflammation, juvenile xanthogranuloma, Whipples disease and malacoplakia are discussed as well. We also briefly go into primary histiocytic disorders of neoplastic origin, systemic diseases with secondary gastrointestinal tract involvement like the lysosomal storage disorders, and pigmented lesions. Using a panel of histochemical stains and immunohistochemical markers, together with conventional microscopy, clinical information, and imaging studies, the diagnosis of histiocytic disorders of the gastrointestinal tract can be established in most instances.

Circulating microRNAs as biomarkers of adult Crohn's disease.

Objective Previous studies have found a differential expression of microRNAs (miRNAs) in the blood of patients with Crohn’s disease (CD) compared with healthy controls. The aim of this study was to identify circulating miRNAs expressed in CD and assess their performance as biomarkers in patients with clinically suspected or known CD. Methods The study consisted of two parts: (a) miRNA profiling: The miRNA expression pattern was examined in six patients with CD and six controls using OpenArray miRNA profiling, and the best miRNAs were selected according to their P-value. (b) Validation cohort: In a well-characterized cohort of 102 patients with suspected or known CD, miRNAs identified by miRNA profiling or selected from previously published studies (hsa-miR-16, hsa-miR-21, hsa-miR-106a, and hsa-miR-140-3p) were measured in plasma using reverse transcription PCR. Results miRNA profiling: hsa-miR-369-3p, hsa-miR-376a, hsa-miR-376, hsa-miR-411#, hsa-miR-411, and mmu-miR-379 were downregulated in CD patients compared with the controls; hsa-miR-200c, hsa-miR-181-2#, and hsa-miR-125a-5p were upregulated (P<0.05). Validation cohort: Only hsa-miR-16 was significantly downregulated in patients with CD compared with patients without CD (fold change 0.83, P=0.02). Receiver operating characteristic analyses showed an area under the curve of 0.65. miRNAs could not discriminate inflammatory from stricturing CD or small bowel CD from CD involving the colon. Conclusion In a clinically relevant cohort of patients, miRNAs in plasma identified in the present and previous studies were inadequate biomarkers for the diagnosis of CD.

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

Capsule endoscopy (CE) has a high sensitivity for diagnosing small bowel Crohns 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 Crohns disease.

Inter-observer Agreement for Detection of Small Bowel Crohn’s Disease with Capsule Endoscopy

Objective. Compared to other modalities, capsule endoscopy (CE) has a high diagnostic yield for diagnosing small bowel Crohn’s disease (CD). The aim of this study was to determine the inter-observer agreement for detection of small bowel CD with predefined diagnostic criteria. Material and methods. Thirty patients with suspected or known CD were included in the study. Observers were blind to patient histories, the results of ileo-colonoscopies, and small bowel examinations. More than three ulcerations (aphthous lesions or ulcers) or the presence of stenosis caused by inflammation or fibrosis was diagnostic of small bowel CD. Three observers with experience in gastrointestinal endoscopy and CE participated in the study. Results. The presence or absence of small bowel CD was determined with complete agreement in 23 patients, nine patients with and 14 without small bowel CD. The inter-observer agreement was substantial for the diagnosis ( k= 0.68) and moderate for the localization of CD ( k= 0.44). Aphthous lesions were detected with only fair agreement ( k= 0.38). The time intervals to passage of the pylorus and ileo-caecal valve were detected with excellent intra-class correlation. Conclusions. CE is performed with substantial inter-observer agreement for detection of small bowel CD. In the majority of patients, the presence or absence of small bowel CD is unequivocal. However, in patients with few or minor lesions, the diagnosis is observer dependent.