Intestinal MRI in Inflammatory Bowel Disease - Literature and Survey-Based Recommendations regarding Reporting by the German Radiological Society (DRG) and the German Competence Network for Inflammatory Bowel Diseases. / Intestinale MRT bei chronisch-entzündlichen Darmerkrankungen ­ Literatur- und umfragebasierte Empfehlungen zur Befundung durch die AG Gastrointestinal-/Abdominaldiagnostik der DRG und der AG Bildgebung des Kompetenznetz Darmerkrankungen.

BACKGROUND: MR-enterography/enteroclysis (MRE) is increasingly used for primary diagnosis, detection of complications, and monitoring of patients with inflammatory bowel disease (IBD). Standardization of reporting is relevant to ensure quality of the methodology and to improve communication between different faculties. The current manuscript describes the features that are required for optimized reporting of MRE in IBD. METHODS: An expert consensus panel of radiologists and gastroenterologists conducted a systematic search of the literature. In a Delphi process, members of the German Radiological Society (DRG) and members of the Competence Network for Inflammatory Bowel Diseases voted on relevant criteria for the reporting of findings in MRE. Based on the voting results, statements were developed by the expert consensus panel. RESULTS: Clinically relevant aspects of MRE findings have been defined to optimize reporting and to standardize terminology. Minimal requirements for standardized reporting are suggested. The statements focus on the description of disease activity as well as on complications of IBD. Attributes of intestinal inflammation are described and illustrated by exemplary images. CONCLUSION: The current manuscript provides standardized parameters and gives practical recommendations on how to report and how to characterize MRE findings in patients with IBD. KEY POINTS: · Systematic overview provides practice-oriented recommendations and names and evaluates the decisive criteria for reporting and interpretation of MRI in inflammatory bowel disease.. · Standardized terminology and reporting criteria for MRI in IBD improves interdisciplinary communication.. · Standardized collection and documentation of MRI findings in IBD helps to further establish the method and to improve care for IBD patients.. CITATION FORMAT: · Wessling J, Kucharzik T, Bettenworth D et al. Intestinal MRI in Inflammatory Bowel Disease - Literature and Survey-Based Recommendations regarding Reporting by the German Radiological Society (DRG) and the German Competence Network for Inflammatory Bowel Diseases. Fortschr Röntgenstr 2023; 195: 675 - 690.

Detection and differentiation of inflammatory versus fibromatous Crohn's disease strictures: prospective comparison of 18F-FDG-PET/CT, MR-enteroclysis, and transabdominal ultrasound versus endoscopic/histologic evaluation.

BACKGROUND: Differentiation between inflammatory and fibromatous strictures in Crohn's disease (CD) is difficult but crucial for therapeutic decisions. The aim of this study was to assess the best noninvasive imaging method for the detection and differentiation of inflammatory and fibromatous stenoses in CD in comparison to endoscopic and histologic evaluation. METHODS: Patients with suspected CD strictures were included. According to a formalized endoscopic and histologic protocol, strictures were classified as inflammatory, mixed, and fibrostenotic. Strictures were further analyzed using fluorine 18-labeled fluoro-2-deoxy-D-glucose ((18) FDG) / positron emission tomography (PET) low-dose computed tomography (CT), magnetic resonance (MR) enteroclysis and transabdominal ultrasound using standardized scoring systems. RESULTS: Thirty patients with 37 strictures were evaluated (inflamed n = 22; mixed n = 12, fibromatous n = 3). (18) FDG-PET/CT detected 81%, MR-enteroclysis 81%, and ultrasound 68% of the strictures. Correct differentiation rates of strictures were 57% for MRE, 53% for (18) FDG-PET/CT, and 40% for ultrasound. Differences of detection rates and differentiation rates were not statistically significant. When combining transabdominal ultrasound with (18) FDG-PET/CT or MR-enteroclysis all strictures that required invasive treatment were detected. CONCLUSIONS: Detection rates of the strictures were not significantly different between (18) FDG-PET/CT, MR-enteroclysis, and ultrasound. Despite good stricture detection rates relating to our gold standard, (18) FDG-PET/CT nor MR-enteroclysis nor ultrasound can accurately differentiate inflamed from fibrotic strictures. A combination of MR-enteroclysis and ultrasound as well as a combination of (18) FDG-PET/CT and ultrasound resulted in a 100% detection rate of strictures requiring surgery or endoscopic dilation therapy, suggesting the combination of these methods as an alternative to endoscopy at least in the group of patients not able to perform an adequate bowel preparation.

The mucosal addressin cell adhesion molecule antibody PF-00547,659 in ulcerative colitis: a randomised study.

BACKGROUND AND AIMS: Leucocyte migration to gut mucosa, mediated by integrin binding to mucosal addressin cell adhesion molecule (MAdCAM), is a promising target for therapeutic intervention in inflammatory bowel disease. This first-in-human study of a monoclonal antibody to MAdCAM, PF-00547,659, aimed to explore the safety and preliminary efficacy of this gut-specific mechanism in ulcerative colitis. METHODS: In this randomised, double-blind placebo-controlled study, 80 patients with active ulcerative colitis received single or multiple (three doses, 4-week intervals) doses of PF-00547,659 0.03-10 mg/kg IV/SC, or placebo. Safety was assessed by adverse events, laboratory tests, and immunogenicity. Exploratory efficacy analyses were based on Mayo score and endoscopic responder rates at weeks 4 and 12. Faecal calprotectin was quantified as a measure of disease activity, and the number of α4ß7⁺ lymphocytes was measured to demonstrate drug activity. RESULTS: No obvious drug-related side effects were observed in the PF-00547,659 group, while patient numbers, especially those fully exposed, were small. Overall responder/remission rates at 4 and 12 weeks were 52%/13% and 42%/22%, respectively with combined PF-00547,659 doses compared with 32%/11% and 21%/0%, respectively with placebo. Equivalent endoscopic responder rates were 50% and 42% versus 26% and 29%, respectively. Faecal calprotectin levels decreased to a greater extent with PF-00547,659 than placebo (week 4: 63% vs 18%). Despite variability, there was a trend for an increase in α4ß7⁺ lymphocytes in patients receiving PF-00547,659. CONCLUSIONS: The favourable short-term safety profile and preliminary efficacy findings for PF-00547,659 in this first-in-human study pave the way for further investigation in larger trials, to establish the role of PF-00547,659 in ulcerative colitis treatment. Trial Register No: NCT00928681.

Enoxaparin improves the course of dextran sodium sulfate-induced colitis in syndecan-1-deficient mice.

Syndecan-1 (Sdc1) plays a major role in wound healing and modulates inflammatory responses. Sdc1 expression is reduced in lesions of patients with ulcerative colitis. The aim of this study was to investigate the role of Sdc1 in murine dextran sodium sulfate (DSS)-induced colitis. DSS colitis was induced in Sdc1-deficient (knockout (KO)) and wild-type mice by oral administration of 3% DSS. KO mice exhibited a significantly increased lethality as compared with wild-type controls (61 versus 5%, P < 0.05). Impaired mucosal healing and prolonged recruitment of inflammatory cells in KO mice were accompanied by significant up-regulation of tumor necrosis factor-alpha, CC chemokine ligand 3/macrophage inflammatory protein-1alpha, and vascular cell adhesion molecule-1, as determined by histological correlation between 0 and 15 days after colitis induction, TaqMan low-density array analysis, and quantitative real-time PCR. Treatment from days 7 through 14 with enoxaparin, a functional analogue of the Sdc1 heparan sulfate chains, significantly reduced lethality of KO mice due to DSS-induced colitis, which was correlated with improved mucosal healing. In vitro, Sdc1-deficient polymorphonuclear cells displayed increased adhesion to endothelial cells and intercellular adhesion molecule-1, and enoxaparin reverted adhesion to wild-type levels. Small interfering RNA-mediated knockdown of Sdc1 expression resulted in reduced basic fibroblast growth factor-mediated mitogen-activated protein kinase signaling and reduced Caco-2 cell proliferation. We conclude that Sdc1 has a protective effect during experimental colitis. The modification of missing Sdc1 function by heparin analogues may emerge as a promising anti-inflammatory approach.

Heterotopic ileal pancreas with lipoma and coexisting fibromatosis associated with a rare case of gastrointestinal bleeding. A case report and review of the literature.

CONTEXT: The development of pancreatic tissue outside the confines of the main gland represents a congenital abnormality referred to as heterotopic pancreas. This is a rare pathological and surgical entity which remains mostly asymptomatic. CASE REPORT: We present the case of a 28-year-old male, who was admitted to hospital because of a history of blood in bowel movements. After a normal gastroscopy and colonoscopy, Tc99m-tagged red blood cells scintigraphy showed enrichment in the right lower abdomen. At double-balloon endoscopy, a intraluminal polypoid mass 8 cm in diameter was revealed 120 cm from the ileocecal valve. The initial macroscopic diagnosis was a gastrointestinal stromal tumor. During surgery, the diagnosis of heterotopic pancreas with lipoma and fibromatosis was made. To our knowledge this is the first case of ileal heterotopic pancreatic tissue and lipoma described to date in the literature. CONCLUSION: Ileal heterotopic pancreas is a rare entity with potentially life-threatening complications, local excision being the appropriate indicated treatment.

Double balloon enteroscopy: a useful tool for diagnostic and therapeutic procedures in the pancreaticobiliary system.

OBJECTIVES: Diagnostic and therapeutic interventions in the biliary and pancreatic system in the previously operated patient by conventional endoscopic retrograde cholangiopancreaticography (ERCP) are difficult and, depending on the surgical procedure, in many cases unsuccessful. We describe our experience of ERCP performed with a double balloon enteroscope (DBE) as an alternative examination technique for these patients. METHODS: In a retrospective analysis of all DBE procedures at our department between November 2004 and June 2007, 11 patients were identified with various anatomic variations in whom ERCP was performed using a DBE. RESULTS: In 72% of the patients, previous conventional ERCP examinations failed (8/11). In these patients, DBE-ERCP was successful in 63%. The overall success rate of DBE-ERCP in all patients was 64% (7/11 patients). In those patients, interventions such as papillotomy, calculus extractions, as well as stent placement could be performed even though tools for DBE-ERCP are still very limited. Despite most of the DBE-ERCPs having included therapeutic interventions, no major complications occurred in our case series and minor side effects were restricted to meteorism and mild to moderate abdominal pain. CONCLUSIONS: DBE-ERCP is an alternative method for diagnostic as well as therapeutic interventions in the biliary as well pancreatic system in the operated patient. However, it should be limited to selected patients, e.g., with contraindications for PTC, as it is a time-consuming as well as a cost-intensive procedure.

Melanocortin-derived tripeptide KPV has anti-inflammatory potential in murine models of inflammatory bowel disease.

BACKGROUND: Despite some progress in recent years, the options for treating inflammatory bowel disease (IBD) are still dissatisfying, and surgery rates are still high. The anti-inflammatory effects of melanocortin peptides such as alpha-melanocyte-stimulating hormone (alpha-MSH) have been described recently in, for example, dextran sodium sulfate (DSS) colitis in mice. The aim of this study was to investigate the therapeutic potential of the melanocortin-derived tripeptide alpha-MSH(11-13) (KPV) and its mode of action in 2 models of intestinal inflammation. METHODS: The anti-inflammatory activity of KPV was analyzed in 2 well-described models of IBD: DSS colitis, and CD45RB(hi) transfer colitis. Furthermore, animals expressing a nonfunctional melanocortin-1 receptor (MC1Re/e) received DSS for induction of colitis and were treated with KPV. The course of inflammation was monitored by weight loss and histological changes in the colon as well as by myeloperoxidase (MPO) activity. RESULTS: In the DSS-colitis model, treatment with KPV led to earlier recovery and significantly stronger regain of body weight. Histologically, inflammatory infiltrates were significantly reduced in KPV-treated mice, which was confirmed by the significant reduction of MPO activity in colonic tissue after KPV treatment. Supporting these findings, KPV treatment of transfer colitis led to recovery, regain of body weight, and reduced inflammatory changes histologically. In MC1Re/e mice, KPV treatment rescued all animals in the treatment group from death during DSS colitis. CONCLUSIONS: The melanocortin-derived tripeptide KPV showed significant anti-inflammatory effects in 2 murine models of colitis. These effects seem to be at least partially independent of MC1R signaling. In conclusion, our data suggest KPV as an interesting therapeutic option for the treatment of IBD.

Preterm birth but not mode of delivery is associated with an increased risk of developing inflammatory bowel disease later in life.

BACKGROUND: Exposure to bacterial antigens and other environmental factors in combination with a genetic susceptibility have been implicated in the etiology of inflammatory bowel disease (IBD). As certain perinatal circumstances, e.g., delivery by cesarean section, predispose to a different intestinal colonizations the aim of this analysis was to define a potential influence on the development of IBD in later life. METHODS: In a case-control study design, birth data were recorded from patients diagnosed with IBD (Crohn's disease [CD], n = 1,096; ulcerative colitis [UC], n = 763) and healthy controls ([C], n = 878) by a self-administered questionnaire. RESULTS: Preterm birth (CD: odds ratio [OR] 1.5 [95% confidence interval 1.1-2.0], UC: OR 1.3 [0.9-1.9]), mother's disease during pregnancy (CD: OR 1.9 [1.3-2.9], UC: OR 1.6 [1.0-2.4]), and disease in the first year of life (CD: OR 2.2 [1.6-2.9], UC: OR 1.7 [1.3-2.3]) are associated with the development of IBD in later life. No significant associations were found for the mode of delivery and breast feeding. In a logistic regression analysis female sex, smoking, appendectomy, maternal IBD, and disease in the first year of life were independently associated with CD. Female sex, appendectomy, and disease in the first year of life were independently associated with UC. CONCLUSIONS: Preterm birth and other perinatal circumstances are associated with the development of IBD, of which disease in the first year of life is an independent risk factor in multivariate analysis.

Proinflammatory cytokines disrupt epithelial barrier function by apoptosis-independent mechanisms.

It is well known that inflammatory conditions of the intestinal mucosa result in compromised barrier function. Inflammation is characterized by an influx into the mucosa of immune cells that influence epithelial function by releasing proinflammatory cytokines such as IFN-gamma and TNF-alpha. Mucosal barrier function is regulated by the epithelial apical junctional complex (AJC) consisting of the tight junction and the adherens junction. Since the AJC regulates barrier function, we analyzed the influence of IFN-gamma and TNF-alpha on its structure/function and determined the contribution of apoptosis to this process using a model intestinal epithelial cell line, T84, and IFN-gamma and TNF-alpha. AJC structure/function was analyzed by confocal microscopy, biochemical analysis, and physiologic measurement of epithelial gate/fence function. Apoptosis was monitored by determining cytokeratin 18 cleavage and caspase-3 activation. IFN-gamma induced time-dependent disruptions in epithelial gate function that were potentiated by coincubation with TNF-alpha. Tight junction fence function was somewhat disrupted. Cytokine treatment was associated with internalization of AJC transmembrane proteins, junction adhesion molecule 1, occludin, and claudin-1/4 with minimal effects on the cytoplasmic plaque protein zonula occludens 1. Detergent solubility profiles of junction adhesion molecule 1 and E-cadherin and their affiliation with "raft-like" membrane microdomains were modified by these cytokines. Inhibition of cytokine-induced apoptosis did not block induced permeability defects; further emphasizing their primary influence on the epithelial AJC structure and barrier function. Our findings for the first time clearly separate the proapoptotic effects of IFN-gamma and TNF-alpha from their abilities to disrupt barrier function.

CCL9 is secreted by the follicle-associated epithelium and recruits dome region Peyer's patch CD11b+ dendritic cells.

The follicle-associated epithelium (FAE) secretes chemokines important in the recruitment of various cell types including CCL20 (MIP-3alpha). CCL20 is chemotactic to the CD11b(+) dendritic cells (DCs) distributed in the subepithelial dome regions of the Peyer's patches, and mice deficient in the receptor for CCL20, CCR6, have been reported to be devoid of the CD11b(+) DCs in the dome regions. Here, we describe another chemokine specifically secreted from the FAE of mouse Peyer's patches, CCL9 (MIP-1gamma, CCF18, MRP-2). By in situ hybridization, we demonstrated that CCL9 mRNA was expressed by the FAE but not by the villus epithelium. At the protein level, CCL9 was detected on the FAE and on extracellular matrix structures within the dome regions of the Peyer's patches. By RT-PCR, we demonstrated that one of the putative receptors for CCL9, CCR1, was expressed by the Peyer's patch CD11b(+) DCs and in a chemotaxis assay, CD11b(+) DCs migrated toward CCL9. To compare the abilities of the chemokines CCL20 and CCL9 to recruit CD11b(+) DCs to the dome regions, we examined the in vivo distribution of these cells in CCR6-deficient, CCL9-blocked wild type, or CCL9-blocked CCR6-deficient mice. To our surprise, using a sensitive immunofluorescence analysis, we observed that CD11b(+) DCs were present in the dome regions of the CCR6-deficient mice. In contrast, Ab neutralization of CCL9 in vivo resulted in significant reduction of the CD11b(+) DC number in the subepithelial dome regions of Peyer's patches of both wild type and CCR6 -/- mice. Taken together, these results demonstrate an important role of CCL9 in CD11b(+) DC recruitment to the dome regions of mouse Peyer's patches.