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].

Objective: In mice, a subpopulation of gut dendritic cells (DCs) expressing CD103 drives the development of regulatory T (T _reg ) cells. Further, it was recently described that the cross-talk between human intestinal epithelial cells (IECs) and DCs helps in maintaining gut immune homeostasis via the induction of non-inflammatory DCs. In this study, an analysis was carried out to determine whether IECs could promote the differentiation of CD103 ⁺ tolerogenic DCs, and the function of primary CD103 ⁺ DCs isolated from human mesenteric lymph nodes (MLNs) was evaluated. Methods: Monocyte-derived DCs (MoDCs) and circulating CD1c ⁺ DCs were conditioned or not with supernatants from Caco-2 cells or IECs isolated from healthy donors or donors with Crohn’s disease and analysed for their ability to induce T _reg cell differentiation. In some cases, transforming growth factor β (TGFβ), retinoic acid (RA) or thymic stromal lymphopoietin (TSLP) were neutralised before conditioning. CD103 ⁺ and CD103 ⁻ DCs were sorted by fluorescence-activated cell sorting (FACS) from MLNs and used in T _reg cell differentiation experiments. Results: It was found that human IECs promoted the differentiation of tolerogenic DCs able to drive the development of adaptive Foxp3 ⁺ T _reg cells. This control was lost in patients with Crohn’s disease and paralleled a reduced expression of tolerogenic factors by primary IECs. MoDCs differentiated with RA or IEC supernatant upregulated the expression of CD103. Consistently, human primary CD103 ⁺ DCs isolated from MLNs were endowed with the ability to drive T _reg cell differentiation. This subset of DCs expressed CCR7 and probably represents a lamina propria-derived migratory population. Conclusions: A population of tolerogenic CD103 ⁺ DCs was identified in the human gut that probably differentiate in response to IEC-derived factors and drive T _reg cell development.

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

Background & Aims: Because the reoperation rate for Crohn’s disease is high after resective surgery, use of conservative surgery has increased. Mesalamine was investigated for the prevention of postoperative relapse, with disappointing results. The role of azathioprine in the postoperative setting is unknown. We aimed to compare the efficacy and safety of azathioprine and mesalamine in the prevention of clinical and surgical relapse in patients who have undergone conservative surgery for Crohn’s disease. Methods: In a prospective, open-label, randomized study, 142 patients received azathioprine (2 mg · kg⁻¹ · day⁻¹) or mesalamine (3 g/day) for 24 months. Clinical relapse was defined as the presence of symptoms with a Crohn’s Disease Activity Index score >200 and surgical relapse as the presence of symptoms refractory to medical treatment or complications requiring surgery. Results: After 24 months, the risk of clinical relapse was comparable in the azathioprine and mesalamine groups, both on intention-to-treat (odds ratio [OR], 2.04; 95% confidence interval [CI], 0.89–4.67) and per-protocol analyses (OR, 1.79; 95% CI, 0.80–3.97). No difference was observed with respect to surgical relapse at 24 months between the 2 groups. In a subgroup analysis, azathioprine was more effective than mesalamine in preventing clinical relapse in patients with previous intestinal resections (OR, 4.83; 95% CI, 1.47–15.8). More patients receiving azathioprine withdrew from treatment due to adverse events than those receiving mesalamine (22% vs. 8%; P = 0.04). Conclusions: While no difference was observed in the efficacy of azathioprine and mesalamine in preventing clinical and surgical relapses after conservative surgery, azathioprine is more effective in those patients who have undergone previous intestinal resection.

The goal of this consensus initiated by the European Crohn’s and Colitis Organisation [ECCO] and European Society of Colo-Proctology [ESCP] was to establish European consensus guidelines for the surgical treatment of Crohn’s disease [CD]. 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 among members of the ESCP, surgeons of ECCO, and ECCO members. Participants were selected by the Guidelines’ Committee of ECCO [GuiCom] and the guideline committee of the ESCP on the basis of their publication record and personal statement. Five working groups [WGs] were formed: WG 1, perioperative management; WG 2, upper gastrointestinal tract and small bowel; WG 3, large bowel; WG 4, perianal CD; and WG 5, special conditions. Participants were asked to answer relevant questions on current practice and areas of controversy related to the surgical treatment of CD based on their experience as well as evidence from the literature [Delphi procedure].¹ In parallel, the WG members performed a systematic literature search of their topic with the appropriate key words using Medline/PubMed/ISI/Scopus, and the Cochrane database, as well as their own files. Provisional guideline statements [with supporting text] were then written by the WG chairs based on answers to the questionnaire and were subsequently circulated among the WG members, prompting discussion and exchange of available evidence. The proposed statements and the supporting text were submitted to an online platform for discussion and two online voting rounds were conducted. The first round involved all participants of the consensus development process and, for the second voting round, all national representatives of ECCO and ESCP were invited to participate. The consensus participants finally met in Dublin on September 22, 2015 for face-to-face discussion and voting for consensus on the statements. This was done by projecting the statements and revising them on screen until consensus was reached. Consensus was defined as agreement by more than 80% of participants; the consensus statements were numbered for convenience in the document. The level of evidence was graded according that published by the Oxford Centre for Evidence-based Medicine 2011 [http://www.cebm.net/mod_product/design/files/CEBM-Levels-of-Evidence-2.1.pdf]. The final manuscript was written by the WG chairs [OZ, GS, JW, WB, ZS] in conjunction with the WG members and revised for consistency by WB and AD. Officially, WB is representing the ECCO and AD the ESCP. It was agreed to publish the consensus guideline in JCC and to post links to the original publication in JCC on the websites of ECCO and the ESCP.