Gut Barrier Dysfunction-A Primary Defect in Twins with Crohns Disease Predominantly Caused by Genetic Predisposition

Background and Aims: The aetiology of Crohns disease is poorly understood. By investigating twin pairs discordant for Crohns disease, we aimed to assess whether the dysregulated barrier represents a cause or a consequence of inflammation and to evaluate the impact of genetic predisposition on barrier function. Methods: Ileal biopsies from 15 twin pairs discordant for Crohns disease [monozygotic n = 9, dizygotic n = 6] and 10 external controls were mounted in Ussing chambers to assess paracellular permeability to (51)Chromium [Cr]-EDTA and trancellular passage to non-pathogenic E. coli K-12. Experiments were performed with and without provocation with acetylsalicylic acid. Immunofluorescence and ELISA were used to quantify the expression level of tight junction proteins. Results: Healthy co-twins and affected twins displayed increased Cr-51-EDTA permeability at 120 min, both with acetylsalicylic acid [p amp;lt; 0.001] and without [p amp;lt; 0.001] when compared with controls. A significant increase in Cr-51-EDTA flux was already seen at 20 min in healthy monozygotic co-twins compared with controls [p amp;lt;= 0.05] when stratified by zygosity, but not in healthy dizygotic co-twins. No difference in E. coli passage was observed between groups. Immunofluorescence of the tight junction proteins claudin-5 and tricellulin showed lower levels in healthy co-twins [p amp;lt; 0.05] and affected twins [p amp;lt; 0.05] compared with external controls, while ELISA only showed lower tricellulin in Crohns disease twins [p amp;lt; 0.05]. Conclusion: Our results suggest that barrier dysfunction is a primary defect in Crohns disease, since changes were predominantly seen in healthy monozygotic co-twins. Passage of E. coli seems to be a consequence of inflammation, rather than representing a primary defect.Funding Agencies|Swedish Research Council-Medicine [VR-MH 2014-02537, 521-2011-2764]; Region Ostergotland, ALF research funds of Linkoping University</p

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

Colonic spirochetosis is associated with colonic eosinophilia and irritable bowel syndrome in a general population in Sweden

Irritable bowel syndrome (IBS) is a functional disorder defined by symptoms in the absence of overt pathology. Colonic spirochetosis (CS), defined by histologic observation of spirochetal strains of Brachyspira in colonic biopsies, is uncommon and considered of doubtful significance. We aimed to determine the prevalence of CS in the general population, identify subtle colon pathologies, and evaluate a link with symptoms of IBS. Colonoscopy was performed in 745 subjects (aged 19-70 years, mean age 51 years, 43% male) with biopsies (ileum and 4 colonic sites) from a random population sample, Stockholm, Sweden, who completed a validated questionnaire of gastrointestinal symptoms; IBS was identified by Rome III criteria. CS was identified by histology and immunohistochemistry. In a general population, 17 individuals (2.28%; 95% confidence interval, 1.2%-3.5%) were diagnosed as having CS by histology; 6 (35%) had IBS. CS was always present in the sigmoid colon, but only 14 rectal biopsies. Eosinophils were increased in colon biopsies in CS cases versus controls, in the transverse (P = .02), sigmoid colon (P = .001), and rectum (P = .0005) with subepithelial eosinophil clusters (P = .053). Lymphoid follicles (at any site) were present in 13 CS (P = .0003). There was a 3-fold increased risk of IBS in CS (odds ratio, 3.59; 95% confidence interval, 1.27-10.11; P = .015). Polyps and diverticular disease were similar in CS cases and controls. The prevalence of CS in a general population is 2% and associated with nonconstipating IBS. Colonic eosinophilia with lymphoid follicles may signify the presence of CS.7 page(s

A prospective comparison of fine-needle aspiration cytology and histopathology in the diagnosis and classification of lymphomas

INTRODUCTIONSurgical biopsy examination is the gold standard for lymphoma diagnostics. However, fine-needle aspiration cytology (FNAC) offers several advantages in that it is quick, inexpensive, and the aspiration procedure has very few complications. This prospective study compares the diagnostic outcome between FNAC and surgical biopsy.MATERIALS AND METHODSA total of 103 patients (>15 years) with lymphadenopathy and accessible lymph nodes underwent both diagnostic procedures. Immunophenotyping was performed on both FNAC and histopathological specimens. The updated KIEL classification was used for primary diagnosis and the WHO classification for reclassification.RESULTSFNAC- and histopathology-based diagnoses were concordant in 76 patients. In 10 patients, there was a major diagnostic discordance: four differed with regard to degree of malignancy (low- versus high-grade NHL), three lymphoma versus reactive changes, and three regarding Hodgkin's lymphoma versus anaplastic large cell lymphoma. In 10 patients there was some (minor) discordance regarding subclassification: in eight patients the results of immunophenotyping differed, in two cases there were discrepancies in the cell type classification. In the remaining seven cases, there were diagnostic difficulties due to an insufficient sample. two serious adverse events occurred following surgical biopsy.CONCLUSIONSFNAC is an accurate method in the diagnosis of lymphomas when the cytologic diagnosis is corroborated by immunophenotyping. However, an increasing use of FNAC for primary diagnosis and classification of lymphomas may result in a loss of archival tissue for complementary analyses, reclassification, and research purposes. In addition, some of the lymphoma entities are impossible to diagnose with use of the FNAC technique

Low-dose budesonide for maintenance of clinical remission in collagenous colitis : a randomised, placebo-controlled, 12-month trial

Objective This 1-year study aimed to assess low-dose budesonide therapy for maintenance of clinical remission in patients with collagenous colitis. Design A prospective, randomised, placebo-controlled study beginning with an 8-week open-label induction phase in which patients with histologically confirmed active collagenous colitis received budesonide (Budenofalk, 9 mg/day initially, tapered to 4.5 mg/day), after which 92 patients in clinical remission were randomised to budesonide (mean dose 4.5 mg/day; Budenofalk 3 mg capsules, two or one capsule on alternate days) or placebo in a 12-month double-blind phase with 6 months treatment-free follow-up. Primary endpoint was clinical remission throughout the double-blind phase. Results Clinical remission during open-label treatment was achieved by 84.5% (93/110 patients). The median time to remission was 10.5 days (95% CI (9.0 to 14.0 days)). The maintenance of clinical remission at 1 year was achieved by 61.4% (27/44 patients) in the budesonide group versus 16.7% (8/48 patients) receiving placebo (treatment difference 44.5% in favour of budesonide; 95% CI (26.9% to 62.7%), p&lt;0.001). Health-related quality of life was maintained during the 12-month double-blind phase in budesonide-treated patients. During treatment-free follow-up, 82.1% (23/28 patients) formerly receiving budesonide relapsed after study drug discontinuation. Low-dose budesonide over 1 year resulted in few suspected adverse drug reactions (7/44 patients), all non-serious. Conclusions Budesonide at a mean dose of 4.5 mg/day maintained clinical remission for at least 1 year in the majority of patients with collagenous colitis and preserved health-related quality of life without safety concerns. Treatment extension with low-dose budesonide beyond 1 year may be beneficial given the high relapse rate after budesonide discontinuation