The fifth scientific workshop of the European Crohn’s and Colitis Organization (ECCO) focused on the relevance of fistulas to the disease course of patients with Crohn’s disease (CD). The objectives were to reach a better understanding of the pathophysiological mechanisms underlying the formation of CD fistulas; to identify future topics in fistula research that could provide insights into pathogenesis; to develop novel therapeutic approaches; and to review current therapeutic strategies (with clarification of existing approaches to prevention, diagnosis and treatment). The results of the workshop are presented in two separate manuscripts. This manuscript describes current state-of-the-art knowledge about fistula pathogenesis, including the roles of epithelial-to-mesenchymal transition and cytokine matrix remodelling enzymes, and highlights the common association between fistulas and stenosis in CD. The review also considers the possible roles that genetic predisposition and intestinal microbiota play in fistula development. Finally, it proposes future directions and needs for fistula research that might substantially increase our understanding of this complex condition and help unravel novel therapeutic strategies and specific targets for treatment. Overall, it aims to highlight unanswered questions in fistula research and to provide a framework for future research work.
Background and Aims: Perianal fistulas affect up to one-third of Crohn’s patients during the course of their disease. Despite the considerable disease burden, current treatment options remain unsatisfactory. The Fifth Scientific Workshop [SWS5] of the European Crohn’s and Colitis Organisation [ECCO] focused on the pathophysiology and clinical impact of fistulas in the disease course of patients with Crohn’s disease [CD].
Methods: The ECCO SWS5 Working Group on clinical aspects of perianal fistulising Crohn’s disease [pCD] consisted of 13 participants, gastroenterologists, colorectal surgeons, and a histopathologist, with expertise in the field of inflammatory bowel diseases. A systematic review of literature was performed.
Results: Four main areas of interest were identified: natural history of pCD, morphological description of fistula tracts, outcome measures [including clinical and patient-reported outcome measures, as well as magnetic resonance imaging] and randomised controlled trials on pCD.
Conclusions:The treatment of perianal fistulising Crohn’s disease remains a multidisciplinary challenge. To optimise management, a reliable classification and proper trial endpoints are needed. This could lead to standardised diagnosis, treatment, and follow-up of Crohn’s perianal fistulas and the execution of well-designed trials that provide clear answers. The prevalence and the natural history of pCD need further evaluation.
This is the first European Crohn’s and Colitis Organisation [ECCO] consensus guideline that addresses extra-intestinal manifestations [EIMs] in inflammatory bowel disease [IBD]. It has been drafted by 21 ECCO members from 13 European countries. Although this is the first ECCO consensus guideline that primarily addresses EIMs, it is partly derived from, updates, and replaces previous ECCO consensus advice on EIMs, contained within the consensus guidelines for Crohn’s disease1 [CD] and ulcerative colitis2 [UC].
This paper is the second in a series of two publications relating to the European Crohn’s and Colitis Organisation [ECCO] evidence-based consensus on the diagnosis and management of Crohn’s disease [CD] and concerns the surgical management of CD as well as special situations including management of perianal CD and extraintestinal manifestations. Diagnostic approaches and medical management of CD of this ECCO Consensus are covered in the first paper [Gomollon et al. JCC 2016].
Introduction:Anaemia is the most common systemic complication and extraintestinal manifestation of inflammatory bowel disease [IBD].1–3 In the majority of cases, IBD-associated anaemia is a unique example of the combination of chronic iron deficiency and anaemia of chronic disease [ACD].4,5 Other more rare causes of anaemia in IBD include vitamin B12 and folate deficiency, toxic effects of medications, and others. The impact of anaemia on the quality of life of IBD patients is substantial. It affects various aspects of quality of life such as physical, emotional, and cognitive functions, the ability to work, hospitalization, and healthcare costs.6 Anaemia in IBD is not just a laboratory marker; it is a complication of IBD that needs appropriate diagnostic and therapeutic approaches.
Due to the important clinical problem that the risk of malignancy in patients with IBD represents for physicians treating IBD, ECCO planned to initiate a programme to develop a specific Guideline for malignancy.
The aim of this consensus is to establish Guidelines for managing the risk of malignancy, treatment in the event of malignancy and therapy of IBD in the context of a past or current history of malignancy.
Trying to conceive and being pregnant is an emotional period for those involved. In the majority of patients suffering from inflammatory bowel disease, maintenance therapy is required during pregnancy to control the disease, and disease control might necessitate introduction of new drugs during a vulnerable period. In this updated consensus on the reproduction and pregnancy in inflammatory bowel disease reproductive issues including fertility, the safety of drugs during pregnancy and lactation are discussed.
Epidemiological studies demonstrate an increased risk of colorectal cancer in patients with inflammatory bowel disease (IBD). A detailed literature review was conducted on epidemiology, risk factors, pathophysiology, chemoprevention and outcomes of colorectal cancer (CRC) in IBD as part of the 3rd ECCO scientific pathogenesis workshop.
Children and adolescents with Crohn's disease (CD) present often with a more complicated disease course compared to adult patients. In addition, the potential impact of CD on growth, pubertal and emotional development of patients underlines the need for a specific management strategy of pediatric-onset CD. To develop the first evidenced based and consensus driven guidelines for pediatric-onset CD an expert panel of 33 IBD specialists was formed after an open call within the European Crohn's and Colitis Organisation and the European Society of Pediatric Gastroenterolog, Hepatology and Nutrition. The aim was to base on a thorough review of existing evidence a state of the art guidance on the medical treatment and long term management of children and adolescents with CD, with individualized treatment algorithms based on a benefit-risk analysis according to different clinical scenarios. In children and adolescents who did not have finished their growth, exclusive enteral nutrition (EEN) is the induction therapy of first choice due to its excellent safety profile, preferable over corticosteroids, which are equipotential to induce remission. The majority of patients with pediatric-onset CD require immunomodulator based maintenance therapy. The experts discuss several factors potentially predictive for poor disease outcome (such as severe perianal fistulizing disease, severe stricturing/penetrating disease, severe growth retardation, panenteric disease, persistent severe disease despite adequate induction therapy), which may incite to an anti-TNF-based top down approach. These guidelines are intended to give practical (whenever possible evidence-based) answers to (pediatric) gastroenterologists who take care of children and adolescents with CD; they are not meant to be a rule or legal standard, since many different clinical scenario exist requiring treatment strategies not covered by or different from these guidelines.
An expert panel of the European Crohn's and Colitis Organisation (ECCO) and European Society of Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) initiated a consensus process to produce the first pediatric specific ulcerative colitis (UC) guidelines based on a systematic literature review. Treatment strategies must reflect that pediatric-onset UC has a slightly different phenotype than adult-onset disease with more often extensive (pancolitis) and more aggressive disease course. Other pediatric-specific aspects include growth, puberty, bone density accrual and emotional development and body image acquisition. These differences and others influenced the development of pediatric treatment algorithms. It is recommended that virtually all children with UC must be treated with some maintenance therapy and 5-ASA requirement and dosing are often higher in children. A larger number of children are at risk for steroid-dependency, and this should not be tolerated; steroid sparing strategies with early use of immunosuppressors are recommended in high-risk patients. On the other hand, the safety profile of immunosuppressive therapy in children includes the rare forms of lymphomas and many future treatment years. Colectomy and pouch formation should be balanced in the treatment algorithms against the higher rate of future infertility in girls. The acute and on-going management of pediatric UC should be guided by evidence- and consensus-based balanced decisions, reflecting a vision of long-term treatment goals.
The goal of this consensus initiated by the European Crohn's and Colitis Organisation (ECCO) was to establish European consensus guidelines for the surgical treatment of ulcerative colitis. The strategy to reach the consensus involved several steps and follows the standard operating procedures for consensus guidelines of ECCO. An open call for chairs and participants for this consensus was made (see acknowledgements and www.ecco-ibd). Participants were selected by the Guidelines' Committee of ECCO (GuiCom) on the basis of their publication record and a personal statement. Four working groups (WGs) were formed: WG 1 on the preoperative phase, WG 2 on the intraoperative phase, WG 3 on the postoperative phase and WG 4 on special situations. Participants were asked to answer relevant questions on current practice and areas of controversy related to the surgical treatment of ulcerative colitis based on their experience as well as evidence from the literature (Delphi procedure).
The incidence of lymphoproliferative disorders (LD) is increasing in developed countries. Patients with inflammatory bowel disease (IBD) exposed to thiopurines are at additional risk of three specific forms of LD: Epstein-Barr-Virus-related post-transplant like LD, hepato-splenic T-cell lymphoma and post-mononucleosis lymphoproliferation. The risk of the two latter forms of LD can be reduced when considering specific immunosuppressive strategies in young males. It is still unclear whether the risk of uterine cervix abnormalities is increased in IBD women, irrespective of the use of immunosuppressants. Given the excess risk demonstrated in various other contexts of immunosuppression, it is currently recommended that all women with IBD, particularly those receiving immunosuppressants, strictly adhere to a screening program of cervical surveillance and undergo vaccination against HPV, when appropriate. Patients with IBD receiving immunosuppressants are at increased risk of skin cancers. The risk of non-melanoma skin cancer is notably increased in patients receiving thiopurines. Recent data suggest that the risk of melanoma is mildly increased in patients exposed to anti-TNF therapy. All IBD patients should adhere to a program of sun protection and dermatological surveillance, whose details should take into account the other non-IBD-related risk factors.
Patients with inflammatory bowel diseases (IBD) have an excess risk of certain gastrointestinal cancers. Much work has focused on colon cancer in IBD patients, but comparatively less is known about other more rare cancers. The European Crohn's and Colitis Organization established a pathogenesis workshop to review what is known about these cancers and formulate proposals for future studies to address the most important knowledge gaps. This article reviews the current state of knowledge about small bowel adenocarcinoma, ileo-anal pouch and rectal cuff cancer, and anal/perianal fistula cancers in IBD patients.