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Hart A.L.,IBD Unit | Ng S.C.,Chinese University of Hong Kong
Alimentary Pharmacology and Therapeutics | Year: 2010

Background Management of acute severe ulcerative colitis (UC) is a clinical challenge, with a mortality rate of approximately 1-2%. The traditional management with intravenous corticosteroids has been modified by introduction of ciclosporin and more recently, infliximab. Aim To provide a detailed and comprehensive review of the medical management of acute severe UC. Methods PubMed and recent conference abstracts were searched for articles relating to treatment of acute severe UC. Results Two-thirds of patients respond to intravenous steroids in the short term. In those who fail steroids, low-dose intravenous ciclosporin at 2 mg/kg/day is effective. Approximately 75% and 50% of patients treated with ciclosporin avoid colectomy in the short and long-terms, respectively. Long-term outcome of ciclosporin therapy is improved by introduction of azathioprine on discharge from hospital, together with oral ciclosporin as a bridging therapy. Controlled data show that infliximab is effective as rescue therapy for acute severe UC and the effect appears to be durable, although longer-term follow-up data are needed. Conclusions Both ciclosporin and infliximab have demonstrated efficacy as rescue medical therapies in patients with acute severe UC, but surgery needs to be considered if there is failure to improve or clinical deterioration. © 2010 Blackwell Publishing Ltd.

Soderlund S.,Karolinska Institutet | Granath F.,Karolinska University Hospital | Brostrom O.,Karolinska Institutet | Karlen P.,Karolinska Institutet | And 4 more authors.
Gastroenterology | Year: 2010

Background & Aims: Reported differences in cancer risk between male and female animals after chronic inflammation suggest that estrogen has inflammation-modifying properties. Little is known about these effects in human beings. Inflammatory bowel disease (IBD) is associated with an increased risk of colorectal cancer (CRC); we studied differences in inflammation-associated CRC between men and women patients with IBD. Methods: By using a large population-based cohort (n = 7607) of individuals diagnosed with IBD from 1954 to 1989, we assessed the sex-specific incidence of CRC from 1960 to 2004. Incidence was determined within the cohort (modeled using Poisson regression) and compared with the general population (assessed as standardized incidence ratios) using data from national Swedish health and census registers. Results: During 171,000 person-years of follow-up evaluation, 196 new cases of CRC were observed (123 in males, 73 in females). Males with IBD had a 60% higher risk of CRC (relative risk [RR], 1.6; 95% confidence interval [CI], 1.2-2.2) than females (cumulative incidence 40 years after IBD diagnosis, 8.3% vs 3.5%). Compared with the rate of CRC among the general population, in males with IBD the RR was 2.6 and the 95% CI was 2.2-3.1, whereas in females the RR was 1.9 and the 95% CI was 1.5-2.4. The effect of sex was limited to the period after 10 years of follow-up evaluation (RR, 0.8 before vs 2.2 after), and to patients diagnosed before age 45 (RR, 2.1 before vs 1.0 after). Conclusions: IBD confers a lower risk of CRC to females than to males. © 2010 AGA Institute.

Gecse K.B.,University of Amsterdam | Gecse K.B.,Robarts Research Institute | Bemelman W.,University of Amsterdam | Kamm M.A.,University of Melbourne | And 13 more authors.
Gut | Year: 2014

Objective: To develop a consensus on the classification, diagnosis and multidisciplinary treatment of perianal fistulising Crohn's disease (pCD), based on best available evidence. Methods: Based on a systematic literature review, statements were formed, discussed and approved in multiple rounds by the 20 working group participants. Consensus was defined as at least 80% agreement among voters. Evidence was assessed using the modified GRADE (Grading of Recommendations Assessment, Development, and Evaluation) criteria. Results: Highest diagnostic accuracy can only be established if a combination of modalities is used. Drainage of sepsis is always first line therapy before initiating immunosuppressive treatment. Mucosal healing is the goal in the presence of proctitis. Whereas antibiotics and thiopurines have a role as adjunctive treatments in pCD, anti-tumour necrosis factor (anti-TNF) is the current gold standard. The efficacy of infliximab is best documented although adalimumab and certolizumab pegol are moderately effective. Oral tacrolimus could be used in patients failing anti-TNF therapy. Definite surgical repair is only of consideration in the absence of luminal inflammation. Conclusions: Based on a multidisciplinary approach, items relevant for fistula management were identified and algorithms on diagnosis and treatment of pCD were developed. and treatment of pCD, based on best available evidence and expert opinion in order to offer guidance to clinicians.

Iborra M.,Fundacion Hospital Universitari La Fe | Invernizzi P.,University of California at Davis | Danese S.,Istituto Clinico Humanitas | Danese S.,IBD Unit
Autoimmunity Reviews | Year: 2012

MicroRNAs (miRNAs) have recently emerged as a new class of modulators of gene expression at the post-transcriptional level. The function of miRNA is the control of protein production by targeting mRNAs for translational repression or degradation. MiRNAs play a critical role in many biological processes such as cellular proliferation and maturation, apoptosis, regulation of chronic inflammation and development of cancer. It has recently been discovered that miRNAs are differentially expressed in autoimmune diseases (AID) and miRNA regulation may impact in the development or prevention of AID. In this paper we review the importance of miRNAs in AID in particular in inflammatory bowel disease (IBD). IBD is an AID whose pathophysiology remains uncertain. It is generally hypothesized that IBD is caused by the enteric microflora in genetically predisposed patients with an immune dysregulation in the gastrointestinal tract. Knowing the typical miRNA pattern of IBD will improve our knowledge of the pathogenesis of this disease and will lead to future well-focused projects to study the regulatory function of such miRNAs. Furthermore, it is possible that some miRNAs are specific to IBD and could serve as biomarkers with clinical applications for the diagnosis or assessment of disease activity. © 2010 Elsevier B.V.

Spinelli A.,IBD Surgery Unit | Spinelli A.,University of Milan | Allocca M.,IBD Unit | Jovani M.,IBD Unit | Danese S.,IBD Unit
Alimentary Pharmacology and Therapeutics | Year: 2014

Background One-third of Crohn's disease (CD) patients will undergo abdominal surgery within the first 5 years of diagnosis.Aim To review the available evidence on pre-operative optimisation of CD patients.Methods The literature regarding psychological support, radiological imaging, abdominal abscess management, nutritional support, thromboembolic prophylaxis and immunosuppression in the perioperative setting was reviewed.Results For diagnosis of fistulas, abscesses and stenosis, ultrasonography (US), computed tomography (CT) and magnetic resonance imaging (MRI) have a high diagnostic accuracy. Under either CT or US guidance, it is possible to perform abscess percutaneous drainage (PD), which, with systemic antibiotic therapy, should be the first-line approach to intra-abdominal abscesses. CD patients with weight loss <10% within the last 3-6 months, body mass index < 18.5 kg/m2 and/or albumin levels <30 g/L, are at an increased risk of post-operative complications. Pre-operative nutritional support should be used in these patients. IBD patients undergoing surgery have a higher risk of venous thromboembolic disease than patients with colorectal cancer, and current guidelines recommend that they should receive prophylaxis with heparin. Whether the use of anti-TNF agents before surgery increases the likelihood of post-operative complications, is the subject of much debate. To date, cumulative evidence from most studies (all retrospective) suggests that there is no such risk increment. Prospective studies are necessary to firmly establish this conclusion.Conclusions Preparation for surgery requires close interaction between surgeons, gastroenterologist, radiologists, psychologists and the patient. Correct pre-operative planning of surgical treatment has a major impact on the outcome of such treatment. © 2014 John Wiley & Sons Ltd.

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