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This article is the second in a series of two publications on the European Crohn's and Colitis Organisation [ECCO] evidence-based consensus on the management of Crohn's disease. The first article covers medical management; the present article addresses surgical management, including preoperative aspects and drug management before surgery. It also provides technical advice for a variety of common clinical situations. Both articles together represent the evidence-based recommendations of the ECCO for Crohn's disease and an update of prior ECCO Guidelines., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background and Aims: This study compares the effectiveness of different biologic therapies and sequences in patients with inflammatory bowel disease [IBD] using real-world data from a large cohort with long exposure., Methods: Demographic, disease, treatment, and outcome data were retrieved for patients in the UK IBD BioResource. Effectiveness of treatment was based on persistence free of discontinuation or failure, analysed by Kaplan-Meier survival analysis with inverse probability of treatment weighting to adjust for differences between groups., Results: In total, 13 222 evaluable patients received at least one biologic. In ulcerative colitis [UC] first-line vedolizumab [VDZ] demonstrated superior effectiveness over 5 years compared to anti-tumour necrosis factor [anti-TNF] agents [p = 0.006]. VDZ was superior to both infliximab [IFX] and adalimumab [ADA] after ADA and IFX failure respectively [p < 0.001 and p < 0.001]. Anti-TNF therapy showed similar effectiveness when used as first-line treatment, or after failure of VDZ. In Crohn's disease [CD] we found significant differences between first-line treatments over 10 years [p = 0.045], with superior effectiveness of IFX compared to ADA in perianal CD. Non-anti-TNF biologics were superior to a second anti-TNF after first-line anti-TNF failure in CD [p = 0.035]. Patients with UC or CD experiencing TNF failure due to delayed loss of response or intolerance had superior outcomes when switching to a non-anti-TNF biologic, rather than a second anti-TNF., Conclusions: We provide real-world evidence to guide biologic selection and sequencing in a range of common scenarios. Our findings challenge current guidelines regarding drug selection after loss of response to first anti-TNF treatment., (© The Author(s) 2023. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation.)

Background: Crohn's disease [CD] patients suffer from nutritional deficiencies when in active disease. We aim to examine calorific intake, macronutrient choice, and disordered eating behaviour in patients with active CD., Methods: CD patients with matched healthy volunteers [HV] were recruited. Active disease was defined by faecal calprotectin >250 µg/g, C-reactive protein 83.8 ± 47.1 mg/dL, or active disease seen on endoscopy or imaging. Symptoms were quantified by Harvey‑Bradshaw Index [HBI]. Calorific intake was assessed by 24-h dietary recall. Disordered eating was assessed using validated questionnaires: Binge Eating Scale [BES]; Power of Food Scale [PFS]; Control of Eating Questionnaire [CoEQ]; Dutch Eating Behaviour Questionnaire [DEBQ]; and Three Factor Eating Questionnaire [TFEQ]., Results: Totals of 30 CD (18 male[M]:12 female [F], age 32.3 ± 2.19 years, body mass index [BMI] 24.9 ± 0.8) and 31 matched HV [19 M:12 F, age 32.8 ± 2.0 years, BMI 24.7 ± 0.5] were recruited. Mean faecal calprotectin was 1032.5 ± 176 µg/g, C-reactive protein 8.38 ± 4.71 mg/dL, and HBI 4.8 ± 1. There were no significant differences in calorific intake between groups. Protein intake was lower in the CD cohort [p = 0.03]. Hospital Anxiety and Depression score was higher [p = 0.01] and CoEQ-Positive Mood [p = 0.001] lower in CD. CD patients were characterised by higher BES [p = 0.01] and lower CoEQ Craving Control [p = 0.027], with greater craving for Sweet [p = 0.043] and Savoury [p = 0.021] foods. PFS food Present [p = 0.005], DEBQ Emotional [p =< 0.001], and External Eating [p = 0.022] were significantly higher than among HV., Conclusions: Reduced protein consumption and more prevalent disordered eating behaviour traits were present in CD. Greater binge eating and decreased control of cravings may be attributed to lower mood and higher anxiety observed. Patients may benefit from stronger psychological support with firm dietetic advice for healthy eating.

Background and Aims: Numerous studies have established that mortality risk in inflammatory bowel disease [IBD] patients is higher than in the general population, but the causes of death have seldom been examined. We aimed to describe causes of death in IBD., Methods: A matched cohort study using UK general practice data from Clinical Practice Research Datalink linked to death registration records. We described the distribution of causes of death among IBD patients by age at death and time since IBD diagnosis. We estimated age-specific mortality rates and hazard ratios of death in multivariable Cox proportional hazards models., Results: 20293 IBD patients were matched to 83261 non IBD patients. The mortality rate was 40% higher in IBD patients [2005 deaths] than in non IBD patients [6024 deaths] (adjusted overall hazard ratio: = 1.4, 95% confidence interval [CI]: = 1.4-1.5], with greater risk of death in Crohn's disease [hazard ratio: = 1.6, 1.5-1.7] than in ulcerative colitis [1.3, 1.3-1.4]. Causes attributable to IBD constituted 3.7% of all deaths in ulcerative colitis and 8.3% in Crohn's disease. Among IBD patients, death was less likely to be due to circulatory, respiratory or neoplastic diseases than among non IBD patients. In both IBD and non IBD patients all these causes became more clinically important with advancing age, with the commonest neoplastic cause of death being lung cancer rather than gastrointestinal cancers., Conclusions: IBD patients have an additional risk of death. Most IBD patients die of circulatory or respiratory causes, and the contribution to mortality from long-term complications of IBD is clinically less important., (Copyright © 2016 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com)

Introduction: Clinical management in inflammatory bowel disease (IBD) is constantly changing. Although improvement in symptoms is of paramount importance, using this as the only surrogate marker of disease activity might underestimate disease burden., Sources of Data: New data from randomized clinical trials are now available. Treatment paradigms are constantly changing leading to an evolution in the therapeutic approach in routine IBD practice., Areas of Agreement: Patients with an aggressive disease phenotype should be identified at the onset and treated more intensely in order to achieve long-lasting mucosal remission., Areas of Controversy: Patients who have mild and indolent disease need to be identified and not over treated., Growing Points: The primary endpoint in IBD management should ideally be mucosal healing. Ample data are now available that correlates mucosal healing with surgical-free outcomes with minimal intestinal damage and patient disability. However, the exact degree of mucosal healing that will lead to improved long-term remission, decreased hospital and surgical rates remains unknown., Areas Timely for Developing Research: Clinical translational work is needed to identify novel pathways in IBD pathogenesis that sub-select patients who would benefit by specific-cytokine pathway modulation.

Background: The incidence of obesity is increasing worldwide. Recent evidence shows that the incidence of Crohn's disease (CD) is increasing as well. Adipocytes release a variety of proinflammatory cytokines and peptides. Visceral adiposity may play an important role in the initiation and perpetuation of inflammation in CD. We report on an analysis of body weight in CD clinical trials between 1991 and 2008., Methods: MEDLINE-based databases were searched for randomized controlled trials pertaining to CD. A time-trend analysis was carried out to investigate changes in weight and disease activity over time. Potential correlation between subject weight and clinical activity was studied., Results: Forty randomized controlled trials involving a total of 10,282 patients with CD conducted between 1991 and 2008 were included. No significant change in gender distribution was noted throughout the follow-up. A significant increase in weight (r = 0.360; 95% confidence interval [CI]: 0.4556-0.8813) and body mass index (r = 0.1431; 95% CI: 0.02628-0.2272) was observed over the time period. Study subjects demonstrated a significant increase in clinical disease activity as measured by the Crohn's disease activity index (r = 0.1092; 95% CI: 2.101-9.087) and disease duration (r = 0.06340; 95% CI: 0.02421-0.2530) over the same time period., Conclusions: We demonstrate increasing body weight over time from 1991 to 2008 in CD as evidenced by baseline data from randomized clinical trials. Adiposity may play a potential role in initiating and perpetuating intestinal inflammation, a hypothesis that should be explored further.

The pathogenesis of inflammatory bowel disease (IBD) is multifactorial and results from an interaction between genetic, immunologic, microbial, and environmental factors. Certain drugs could act as a trigger for the disease and have been implicated in the development of new onset IBD in a number a studies. These relationships are based on case reports and cohort studies, as proving this in the context of randomized controlled trials would be difficult. Drugs that have been linked to causing or worsening IBD include isotretinoin, antibiotics, nonsteroidal antiinflammatory drugs, oral contraceptives, mycophenolate mofetil, etanercept, ipilimumab, and rituximab. Bowel preparation for colonoscopy has also been associated with aphthoid lesions that may be confused with IBD. However, given the source of these reports we have to be cautious in the interpretation of the data before concluding that these drugs trigger IBD and what is being observed is not related to other confounding factors. Different pathogenic mechanisms have been suggested for the different drugs listed above. In order to clarify the confusion a comprehensive literature review was performed with the goal of advancing the knowledge on this subject.

Background and Aims: Enteroendocrine cells sense gut luminal contents, and orchestrate digestive physiology whilst contributing to mucosal homeostasis and innate immunity. The terminal ileum is the key site of EEC expression but detailed assessment of their subtypes, lineage transcription factors and expression products has not been undertaken in terminal ileal Crohn's disease. Recent Crohn's disease gene wide association studies have linked the neuroendocrine transcription factor Phox2b; while autoantibodies to an enteroendocrine protein, ubiquitination protein 4a, have been identified as a disease behaviour biomarker., Methods: Terminal ileal tissue from small or large bowel Crohn's disease and normal controls was analysed for enteroendocrine marker expression by immunohistochemistry and quantitative polymerase chain reaction. Inflammation was graded by endoscopic, clinical, histological and biochemical scoring., Results: In small bowel disease, glucagon-like peptide 1 and chromogranin A cells were increased 2.5-fold (p=0.049) and 2-fold (p=0.031) respectively. Polypeptide YY cells were unchanged. Ileal enteroendocrine cell expression was unaffected in the presence of Crohn's colitis. Phox2b was co-localised to enteroendocrine cells and showed a 1.5-fold increase in ileal disease. Significant mRNA increases were noted for chromogranin A (3.3-fold; p=0.009), glucagon-like peptide 1 (3.1-fold; p=0.007) and ubiquitination protein 4a (2.2-fold; p=0.02). Neurogenin 3, an enteroendocrine transcription factor showed ~2 fold-upregulation (p=0.048)., Conclusions: Enhanced enteroendocrine cell activity is present in small bowel disease, and observed in restricted cell lineages. This may impact on the epithelial immune response, cellular homeostasis and nutrient handling and influence appetite via increased satiety signalling in the gut-brain axis., (Copyright © 2012 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.)

Background and Aim: Limited data suggests that pseudomembranes are uncommon in patients with inflammatory bowel disease (IBD) and C. difficile associated disease (CDAD), but the reason for this is unknown. We aimed to evaluate the rate of pseudomembranes in this population, identify predictive factors for pseudomembranes' presence and assess its clinical impact., Methods: This was a sub-study of a retrospective European Crohn's & Colitis Organization (ECCO) multi-center study on the outcome of hospitalized IBD patients with C. difficile. The present study included only patients who underwent lower endoscopy during hospitalization, and compared demographic and clinical parameters in the group of patients with discernable pseudomembranes versus those without., Results: Out of 155 patients in the original cohort, 93 patients underwent lower endoscopy and constituted the study population. Endoscopic pseudomembranes were found in 12 (13%) of these patients. Patients with pseudomembranes presented more commonly with fever (p=0.02) compared to patients without pseudomembranes. No difference between the two groups was found with respect to the use of immunosuppressant drugs, background demographics or disease characteristics. Neither was there a difference between the group with or without pseudomembranes in the frequency of severe adverse clinical outcome or in the duration of hospitalization. On multi-variate analysis the presence of fever remained independently associated with the finding of pseudomembranes (OR 6, 95% CI 1.2-32, p=0.03)., Conclusions: This study documents that hospitalized IBD patients with CDAD have low rate of endoscopic pseudomembranes, which is not accounted for by the use of immunosuppressant drugs. IBD patients with CDAD and discernable pseudomembranes more commonly present with fever, but their clinical outcome is similar to patients without pseudomembranes., (Copyright © 2009 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.)