Capsule Retentions and Incomplete Capsule Endoscopy Examinations: An Analysis of 2300 Examinations

Aim. To evaluate capsule endoscopy in terms of incomplete examinations and capsule retentions and to find risk factors for these events. Material and Methods. This retrospective and consecutive study includes data from 2300 capsule enteroscopy examinations, performed at four different hospitals in Stockholm, Sweden from 2003 to 2009. Results. The frequency of incomplete examinations was 20%. Older age, male gender, suspected, and known Crohn's disease were risk factors for an incomplete examination. The PillCam capsule had the highest rate of completed examinations. Capsule retention occurred in 1.3% (n = 31). Risk factors for capsule retention were known Crohn's disease and suspected tumor. Complications of capsule retention were acute obstructive symptoms in six patients and one death related to complications after acute surgical capsule retrieval. Conclusion: Capsule endoscopy is considered a safe procedure, although obstructive symptoms and serious complications due to capsule retention can be found in a large series of patients

Mouse Model of Alagille Syndrome and Mechanisms of Jagged1 Missense Mutations.

BACKGROUND & AIMS: Alagille syndrome is a genetic disorder characterized by cholestasis, ocular abnormalities, characteristic facial features, heart defects, and vertebral malformations. Most cases are associated with mutations in JAGGED1 (JAG1), which encodes a Notch ligand, although it is not clear how these contribute to disease development. We aimed to develop a mouse model of Alagille syndrome to elucidate these mechanisms. METHODS: Mice with a missense mutation (H268Q) in Jag1 (Jag1+/Ndr mice) were outbred to a C3H/C57bl6 background to generate a mouse model for Alagille syndrome (Jag1Ndr/Ndr mice). Liver tissues were collected at different timepoints during development, analyzed by histology, and liver organoids were cultured and analyzed. We performed transcriptome analysis of Jag1Ndr/Ndr livers and livers from patients with Alagille syndrome, cross-referenced to the Human Protein Atlas, to identify commonly dysregulated pathways and biliary markers. We used species-specific transcriptome separation and ligand-receptor interaction assays to measure Notch signaling and the ability of JAG1Ndr to bind or activate Notch receptors. We studied signaling of JAG1 and JAG1Ndr via NOTCH 1, NOTCH2, and NOTCH3 and resulting gene expression patterns in parental and NOTCH1-expressing C2C12 cell lines. RESULTS: Jag1Ndr/Ndr mice had many features of Alagille syndrome, including eye, heart, and liver defects. Bile duct differentiation, morphogenesis, and function were dysregulated in newborn Jag1Ndr/Ndr mice, with aberrations in cholangiocyte polarity, but these defects improved in adult mice. Jag1Ndr/Ndr liver organoids collapsed in culture, indicating structural instability. Whole-transcriptome sequence analyses of liver tissues from mice and patients with Alagille syndrome identified dysregulated genes encoding proteins enriched at the apical side of cholangiocytes, including CFTR and SLC5A1, as well as reduced expression of IGF1. Exposure of Notch-expressing cells to JAG1Ndr, compared with JAG1, led to hypomorphic Notch signaling, based on transcriptome analysis. JAG1-expressing cells, but not JAG1Ndr-expressing cells, bound soluble Notch1 extracellular domain, quantified by flow cytometry. However, JAG1 and JAG1Ndr cells each bound NOTCH2, and signaling from NOTCH2 signaling was reduced but not completely inhibited, in response to JAG1Ndr compared with JAG1. CONCLUSIONS: In mice, expression of a missense mutant of Jag1 (Jag1Ndr) disrupts bile duct development and recapitulates Alagille syndrome phenotypes in heart, eye, and craniofacial dysmorphology. JAG1Ndr does not bind NOTCH1, but binds NOTCH2, and elicits hypomorphic signaling. This mouse model can be used to study other features of Alagille syndrome and organ development

Bleeding from gastrointestinal angioectasias is not related to bleeding disorders - a case control study

n/aOriginal Publication:Charlotte M Hoog, Olle Brostrom, Tomas Lindahl, Andreas Hillarp, Gerd Larfars and Urban Sjoqvist, Bleeding from gastrointestinal angioectasias is not related to bleeding disorders - a case control study, 2010, BMC GASTROENTEROLOGY, (10), 113.http://dx.doi.org/10.1186/1471-230X-10-113Licensee: BioMed Centralhttp://www.biomedcentral.com

Malignant transformation of the colorectal mucosa in inflammatory bowel disease

Ulcerative colitis (UC) and Crohn's disease (CD) are disorders of unknown etiology, often referred to as inflammatory bowel diseases (IBD). The increased risk of colorectal cancer (CRC) in patients with longstanding, extensive colonic IBD is an important clinical problem. Colonoscopic surveillance, annually or every second year, with multiple biopsies for histopathological detection of dysplasia, is now used to manage this increased risk at many centers for IBD. Dysplasia is a useful prognostic marker for subsequent cancer development but has limitations including substantial inter- and intra-observer variability among pathologists. Furthermore, concomitant active inflammation makes assessment and interpretation of dysplasia difficult. There is a need for more accurate and more objective markers for neoplastic transformation of the colorectal mucosa in high-risk individuals. Although long-term treatment with 5-ASA compounds seems to lower the risk of CRC in IBD, no studies using primarily preventive drugs have been performed. The aims of this thesis were to assess the utility of other markers for malignant transformation of the colorectal mucosa and also to explore any potential chemopreventive properties of long-term oral therapy with ursodeoxycholic acid in high- risk patients with IBD. By using monoclonal antibodies, the expression of the proliferative antigens Ki-67 and PCNA was assessed in biopsy specimens with various degrees of epithelial dysplasia and inflammatory changes. Increased staining with MIB-1 and PCNA correlated with increased severity of dysplasia but also with increased inflammation. In the absence of inflammation, immunostaining with these two antibodies may complement dysplasia, especially in the indefinite changes category. Alkaline sphingomyelinase (SMase) hydrolyses sphingomyelin (SM) generating ceramide which is important in the regulation of cell growth. The activity of alkaline SMase activity is decreased in CRC and premalignant conditions and was also found to be decreased in IBDpatients. There was also an age-dependent decrease of alkaline SMase both in IBD- patients and controls. Flow cytometric DNA-analyses of biopsy specimen can detect gross chromosomal aberrations and also have the ability to correctly estimate the number of cells in proliferation (S-phase). In normal colorectal mucosa it was found that the S-phase increased linearly with age and decreased from the right colon over the transverse colon to the left colon. The fraction of G2cells increased significantly with increased S-phase fraction. No aneuploidy was detected. In 324 UC-patients undergoing colonoscopic surveillance, the S-phase of aneuploid samples was significantly increased compared to diploid, but significantly lowered in comparison with sporadic CRC. An increase in S-phase fraction in patients with IBD without active inflammation may be an additional marker for neoplastic potential in the colorectal mucosa. Ursodeoxycholic acid, a natural bile salt, has been associated with regression of experimentally induced neoplasia in rats. In a two year prospective, double blind randomized pilot study in high-risk IBD-patients, none of the ten patients in the treatment group had progression of dysplasia, while two of the nine patients in the placebo group were refered for colectomy due to progression of dysplasia. UDCA may exert chemopreventive action(s) in patients with longstanding IBD in the colon, but further studies are needed in order to determine optimal selection of patients, UDCA-dose and treatment time

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Bleeding from gastrointestinal angioectasias is not related to bleeding disorders -a case control study Hoog, Charlotte M.; Brostrom, Olle; Lindahl, Tomas L.; Hillarp, Andreas; Larfars, Gerd; Sjoqvist, Urban General rights Copyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights. • Users may download and print one copy of any publication from the public portal for the purpose of private study or research. • You may not further distribute the material or use it for any profit-making activity or commercial gain • You may freely distribute the URL identifying the publication in the public portal ? Take down policy If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim. Download date: 07. Oct. 2016 R E S E A R C H A R T I C L E Open Access Bleeding from gastrointestinal angioectasias is not related to bleeding disorders -a case control study Abstract Background: Angioectasias in the gastrointestinal tract can be found in up to 3% of the population. They are typically asymptomatic but may sometimes result in severe bleeding. The reasons for why some patients bleed from their angioectasias are not fully understood but it has been reported that it may be explained by an acquired von Willebrand syndrome (AVWS). This condition has similar laboratory findings to congenital von Willebrand disease with selective loss of large von Willebrand multimers. The aim of this study was to find out if AVWS or any other bleeding disorder was more common in patients with bleeding from angioectasias than in a control group. Methods: We compared bleeding tests and coagulation parameters, including von Willebrand multimers, from a group of 23 patients with anemia caused by bleeding from angioectasias, with the results from a control group lacking angioectasias. Results: No significant differences between the two groups were found in coagulation parameters, bleeding time or von Willebrand multimer levels. Conclusion: These results do not support a need for routine bleeding tests in cases of bleeding from angioectasias and do not show an overall increased risk of AVWS among these patients

Kolitcancer - mer myt än verklighet?

Patients with ulcerative colitis (UC) and Crohn´s colitis are at increased of developing colorectal cancer (CRC). However, recent studies suggest that the risk is now less than previously thought. Well established risk factors include extent and duration of disease, primary sclerosing cholangitis (PSC) and a family history of CRC. Recently inflammation (both microscopic and macroscopic) has been shown to represent an important independent risk factor for CRC development. Thus one likely explanation for the decreased risk of CRC observed in UC patients is the use of agents that inhibit the inflammatory process, particularly 5-ASA. Ursodeoxycholic acid has been found to be chemopreventive in UC patients with PSC. Evidence from case series and case-control studies suggest that surveillance colonoscopy also reduces the risk of CRC. Prospective randomized controlled trials will never be done because of ethical and logistical concerns. Thus, in the absence of these studies, our knowledge will have to rely on biologic and observational studie