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North Fremantle, Australia

Latella G.,University of LAquila | Rogler G.,University of Zurich | Bamias G.,National and Kapodistrian University of Athens | Breynaert C.,Catholic University of Leuven | And 6 more authors.
Journal of Crohn's and Colitis | Year: 2014

The fourth scientific workshop of the European Crohn's and Colitis Organization (ECCO) focused on the relevance of intestinal fibrosis in the disease course of inflammatory bowel disease (IBD). The objective was to better understand the pathophysiological mechanisms of intestinal fibrosis, to identify useful markers and imaging modalities of fibrosis in order to assess its presence and progression, and, finally, to point out possible approaches for the prevention and the treatment of fibrosis.The results of this workshop are presented in three separate manuscripts. This first section describes the most important mechanisms that contribute to the initiation and progression of intestinal fibrosis in IBD including the cellular and molecular mediators, the extracellular matrix molecules and matrix metalloproteinases/tissue inhibitors of metalloproteinases-system, the microbiota products, the role of fat, genetic and epigenetic factors, as well as the currently available experimental models. Furthermore, it identifies unanswered questions in the field of intestinal fibrosis and provides a framework for future research. © 2014 European Crohn's and Colitis Organisation.

Lawrance I.C.,Center for Inflammatory Bowel Diseases | Lawrance I.C.,University of Western Australia
Journal of Gastroenterology and Hepatology (Australia) | Year: 2011

Rectally administered topical agents have demonstrated efficacy in the maintenance of distal colitis (DC) and proctitis and as they are rarely associated with significant blood drug levels, side effects are infrequent. The topical 5-aminosalicylic acid (5-ASA) suppositories and enemas target different regions of the distal colon and are effective for proctitis and DC, respectively. They demonstrate clinical results that are better than oral 5-ASAs and are preferred to topical steroids with better clinical, endoscopic and histological outcomes, without the risk of adrenal suppression. Disease resistant to topical agents, however, can be extremely difficult to manage. The addition of oral 5ASAs, steroids, immunosuppressants and the anti-tumor necrosis factor-α agents may be effective, but can result in significant side effects and not all patients will respond to the therapies. It is for these patients that new and novel therapies are required. Novel topical agents have been proposed for the management of resistant DC. These agents included butyrate, cyclosporine, and nicotine enemas, as well as tacrolimus suppositories, and tacrolimus, ecabet sodium, arsenic, lidocaine, bismuth, rebamipide and thromboxane enemas. While some of these agents appear to demonstrate impressive outcomes, the majority have only been examined in small open-labeled studies. There is thus a desperate need for more randomized double-blinded placebo controlled studies to investigate the clinical utility of these topical therapies. This review summarizes the efficacy of the established topical therapies, and explores the available data on the new and novel topical agents for the management of DC and proctitis. © 2010 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd.

Lawrance I.C.,University of Western Australia | Lawrance I.C.,Center for Inflammatory Bowel Diseases
Expert Opinion on Investigational Drugs | Year: 2015

Introduction: Ulcerative colitis (UC) is a life-long, immunologically mediated condition that results from an inappropriate activation of the mucosal immune system by intestinal luminal antigens in genetically susceptible individuals. TNF-α is a pro-inflammatory cytokine central to UC pathogenesis. Areas covered: This review examines the evidence for the use of the anti-TNF (αTNF) medications infliximab, adalimumab, certolizumab and golimumab in the management of UC. It highlights the newer biosimilar agents that are becoming available and the early stage investigation of an orally administered αTNF agent. Expert opinion: αTNF therapy is effective but only in a proportion of UC patients. As there is now strong evidence that UC is not just a single disease but a series of phenotypes with distinct genetic, serological and environmental aspects, understanding the heterogeneity of the innate immunological response in UC could allow for better targeted patient management. Identifying differences in the efficacy of the various αTNF agents is difficult as there are no head-to-head studies, but only infliximab has proven clinical efficacy in the management of acute severe colitis. Biosimilars to the αTNF agents are now available and with the added competition, medications costs should fall allowing for greater patient access. © 2015 Informa UK, Ltd.

Lawrance I.C.,Center for Inflammatory Bowel Diseases | Lawrance I.C.,University of Western Australia
World Journal of Gastroenterology | Year: 2014

The inflammatory bowel diseases (IBDs) are chronic incurable conditions that primarily present in young patients. Being incurable, the IBDs may be part of the patient's life for many years and these conditions require therapies that will be effective over the long-term. Surgery in Crohn's disease does not cure the disease with endoscopic recurrent in up to 70% of patients 1 year post resection. This means that, the patient will require many years of medications and the goal of the treating physician is to induce and maintain long-term remission without side effects. The development of the antitumour necrosis factor alpha (TNFα) agents has been a magnificent clinical advance in IBD, but they are not always effective, with loss of response overtime and, at times, discontinuation is required secondary to side effects. So what options are available if of the anti-TNFα agents can no longer be used? This review aims to provide other options for the physician, to remind them of the older established medications like azathioprine/6-mercaptopurine and methotrexate, the less established medications like mycophenolate mofetil and tacrolimus as well as newer therapeutic options like the anti-integins which block the trafficking of leukocytes into the intestinal mucosa. The location of the intestinal inflammation must also be considered, as topical therapeutic agents may also be worthwhile to consider in the longterm management of the more challenging IBD patient. The more options that are available the more likely the patient will be able to have tailored therapy to treat their disease and a better long-term outcome. © 2014 Baishideng Publishing Group Co., Limited. All rights reserved.

Mill J.,Center for Inflammatory Bowel Diseases | Lawrance I.C.,Center for Inflammatory Bowel Diseases | Lawrance I.C.,University of Western Australia
Minerva Gastroenterologica e Dietologica | Year: 2013

Inflammation and immunosuppression are two major risk factors for the development of carcinogenesis in inflammatory bowel disease (IBD). While the natural history of uncontrolled inflammation in the bowel may lead to a higher incidence of colorectal cancer (CRC), surveillance colonoscopy has resulted in earlier detection of dysplasia and cancer, prompting earlier surgical intervention and improved prognosis, while chemoprevention in the form of the anti-inflammatory 5-aminosalicylate acids and immunosuppression could potentially decrease the incidence of CRC. Numerous extra-intestinal cancers such as hepatobiliary and pancreatic malignancies, however, are also noted to be more prevalent in IBD patients particularly with co-existing primary sclerosing cholangitis. Somewhat ironically, however, the medications used to control the inflammation in IBD may also be responsible for the development of other cancers. The increased risk of lymphoma and skin cancers associated with immunosuppressive medication use may potentially be due to loss of immunosurveillance and in the case of lymphoma, the presence of oncogenic viruses (i.e., Epstein-Barr virus). Thus the challenge for both the treating physician and IBD patient is to balance the risk of any potential treatment against patient symptoms and the natural history of uncontrolled inflammation from their disease.

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