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We present a long-term follow-up in a 17-year-old girl with DGAT1-related diarrhea, an autosomal recessive disorder characterized by impaired triglyceride absorption. Neonatal presentation included severe congenital diarrhea, protein-losing enteropathy, and failure to thrive requiring total parenteral nutrition. Duodenal biopsies revealed apoptotic enteropathy and acute inflammation with the presence of macrophages and Touton giant cells, related to the intake of fat. She was able to switch to enteral nutrition on a fat-free diet. However, at age 10, she developed gluten-induced enteropathy and then IBD-like inflammation 5 years later. Immunohistochemistry was able to confirm the diagnosis, while DGAT1 sequencing remained inconclusive. This highlights the role of histopathology and immunohistochemistry, despite the increasing importance of genetic analysis in the diagnostic work-up. This report also illustrates that parenteral nutrition weaning is possible in DGAT1-related diarrhea, but gut barrier dysfunction might increase the risk of autoimmune intestinal disease.

Objective To compare the outcomes of different treatments for spontaneous intra-abdominal abscesses (IAA) in active Crohn's disease (CD). Methods A retrospective analysis of patients with CD between January 2007 and December 2018 was performed in two Belgian inflammatory bowel disease centers. Successful conservative management was defined as complete resolution of abscesses without the need for bowel resection. The primary outcome was suboptimal evolution, defined as a composite outcome of recurrence of abscess, postoperative complications or the need for a non-elective resection. Results Forty CD patients presenting with 43 independent episodes of spontaneous IAA development were included. One underwent immediate bowel resection. In all other 42 cases a conservative approach was taken, which led to a complete abscess resolution rate of 28.6% (12/42). The remaining abscesses required bowel resection. Anti-tumor necrosis factor (TNF) agent use was associated with successful conservative management (odds ratio [OR] 13.36, 95% confidence interval [CI] 11.19-15.52, P = 0.006), while the opposite trend was found for corticosteroids (OR 0.14, 95% CI 0.02-1.26, P = 0.055). There was a trend towards suboptimal evolution in case of previous bowel resection (OR 4.77, 95% CI 0.77-29.66, P = 0.094) or in patients aged above 50 years (OR 5.17, 95% CI 0.86-30.91, P = 0.072). Conclusions Bowel resection appears to be inevitable in most CD patients presenting with IAA. An attempt at conservative treatment may be particularly successful with anti-TNF agents in younger patients who have not undergone previous bowel resection. Large-scale prospective studies are needed to confirm these findings.

Perianal fistulizing Crohn's disease (PFCD) represents a challenging and complex disease phenotype. Patients typically suffer a more severe disease course than those without perianal complications and are often managing debilitating symptoms. Etiology is understood to be multifactorial, with genetic predisposition, microbiological insult, aberrant immunity, and mechanical factors all implicated. As a result, multimodal treatment strategies must be employed to achieve disease control and fistula closure. This requires the complimentary involvement of medical and surgical disciplines in order to ensure thorough assessment and treatment tailored to the individual scenario and patient goals. The aim of this article is to describe an overview of the various treatment strategies available for PFCD, focusing on how a synergistic approach is required to ensure maximal chances of success.

Perianal fistulising Crohn's disease is an aggressive disease phenotype that can have a substantial detrimental impact on patients' quality of life. Current biological understanding of perianal fistulising Crohn's disease remains inadequate and previous classification systems have not provided clear guidance on therapy in clinical practice nor on defining patient cohorts within clinical trials. We propose a new classification system for perianal fistulising Crohn's disease that was developed through a modified nominal group technique expert consensus process. The classification identifies four groups of patients. Key elements include stratification according to disease severity as well as disease outcome; synchronisation of patient and clinician goals in decision making, with a proactive, combined medical and surgical approach, on a treat to patient goal basis; and identification of indications for curative fistula treatment, diverting ostomy, and proctectomy. The new classification retains an element of flexibility, in which patients can cycle through different classes over time. Furthermore, with each specific class comes a paired treatment strategy suggestion and description of clinical trial suitability. The proposed classification system is the first of its kind and is an important step towards tailored standardisation of clinical practice and research in patients with perianal fistulising Crohn's disease.

Introduction Three years after publication of the top 10 research priorities in Inflammatory Bowel Disease (IBD) based on the James Lind Alliance (JLA) Priority Setting Partnership, the question remains whether this initiative has influenced the research landscape.1 Therefore, the aim of this study is to create an overview of the current distribution of the research interests of clinical trials, in adults with IBD, ongoing or completed in the United Kingdom (UK) within the last 3 years. Methods The database from Clinicaltrials.gov and European Union Clinical Trials Register was used to generate a list of all clinical studies set up in the UK involving adult patients with IBD. Trials posted on 09/08/2016 (publication date of the top 10 research questions) up to 16/11/2019 were included. The register was completed by trials found to be relevant based on author consensus. Results Twenty-one non-pharmaceutical-funded clinical studies in the UK were found of which eight were randomised clinical trials, 6 were non-randomised (open label) and 7 were observational studies. As shown in figure 1, 24% of the non-pharmaceutical-driven IBD studies investigated the optimal treatment strategy considering efficacy, safety and cost-effectiveness (immunomodulators, biologics, surgery) in IBD (Priority 1). Four studies evaluated the role of diet in IBD management (Priorities 3 and 7). Development or assessment of biomarkers for stratification of patients (Priority 2) was subject of 3 studies. Fatigue, IBD-related pain, control of diarrhoea and incontinence were each subject of 2 studies (respectively Priorities 4, 8 and 6). Measuring the effect of altered gut microbiota (Priority 10) and determining the optimal treatment strategy for perianal Crohn’s disease (Priority 5) was the target of 2 studies each. One study assessed surgical treatment for terminal ileal Crohn’s disease (Priority 9). Conclusions Optimal treatment strategy and the role of dietary interventions in IBD have been the most commonly studied domains in UK-led trials not sponsored by industry over a three year-period, accounting respectively for 24% and 19% of all studies. However, only 7 studies focused on patient-reported outcomes such as IBD-related pain, fatigue, and diarrhoea/incontinence. As a consequence, it remains debatable to what extent the current landscape of clinical trials adequately represents the patients’ viewpoint on needs for expanded knowledge in IBD. Reference Hart AL, Lomer M, et al. ( 2017) What Are the Top 10 Research Questions in the Treatment of Inflammatory Bowel Disease? A Priority Setting Partnership with the James Lind Alliance. J Crohns Colitis11, 204–211.

BackgroundSince publication of the top 10 research priorities in inflammatory bowel disease (IBD) based on the James Lind Alliance Priority Setting Partnership, the question remains whether this has influenced the IBD-research landscape. This study aimed to create an overview of the current distribution of research interests of trials in the UK.MethodsThe ClinicalTrials.gov database and European Union Clinical Trials Register were screened for clinical trials set up from 9 August 2016 to 16 November 2019 in the UK involving adult patients with IBD.ResultsOf 20 non-industry-sponsored studies, a quarter investigated treatment strategies considering efficacy, safety and cost-effectiveness (priority 1). Four evaluated the role of diet (priorities 3 and 7). Development/assessment of biomarkers for patient stratification (priority 2) and fatigue (priority 8) were subject of three studies. IBD-related pain and control of diarrhoea/incontinence were each subject of 2 studies (priorities 4 and 6). The effect of gut microbiota (priority 10) and optimal strategy for perianal Crohn’s disease (priority 5) was the focus of 2 studies each. One study evaluated surgery for terminal ileal Crohn’s disease (priority 9). Of 63 industry-sponsored studies, 59 focused on priority 1.ConclusionsThis study presents an impression of the breadth of the IBD-research landscape in the UK, in light of the top 10 research priorities published in 2016. Optimal treatment strategy has been the most studied research priority by academic and industry-sponsored trials. Fewer studies focused on patient-reported outcomes. It remains debatable to what extent the current research landscape adequately represents all stakeholders’ viewpoints on needs for expanded knowledge in IBD, particularly the patients’ perspective.

Introduction Colonoscopy prevents colorectal cancer via the detection and resection of premalignant polyps. This effect may be attenuated by variations in polypectomy, with multiple techniques available and a wide range of experience amongst endoscopists. We assessed current practice against the best available contemporary evidence. Methods An online survey was distributed to members of the gastroenterological and surgical societies of seven countries during July 2017. Images of colorectal polyps were presented and respondents requested to provide the polypectomy technique they would employ in their daily practice. Responses were compared to the evidence-based techniques in the 2017 ESGE Colorectal Polypectomy Guideline. Results In total, 707 endoscopists (627 physicians, 71 surgeons, 9 nurse endoscopists, median practice duration 18 years) completed the survey. Of these, 3.1 % selected hot biopsy forceps and 5.2 % hot snare polypectomy (without submucosal lifting) to remove a 3 mm ascending colon polyp. Only 43.3 % selected cold snare polypectomy (CSP) to remove an 8 mm ascending colon polyp. Surgical referral was selected by 16.7 % of respondents for a 45 mm transverse colon polyp without endoscopic evidence of submucosal invasive cancer (SMIC). Endoscopic resection was selected by 12.0 % for an 80 mm sigmoid polyp with imaging consistent with deep SMIC, and a further 26.4 % selected tertiary endoscopist referral, suggesting they had not appreciated that it was endoscopically unresectable. Conclusion CSP is underutilized for small polyp resection despite its favorable safety and efficacy. Benign polyps are commonly referred for surgery and overt SMIC is underappreciated using endoscopic imaging. Addressing these issues may reduce diathermy-related adverse events, surgery, and unnecessary colonoscopic procedures for patients and reduce rates of post-colonoscopy colorectal cancer.

Background Successful personalized treatment in inflammatory bowel disease (IBD) is critically dependent on identifying those patients at greater risk of a complicated disease course and who therefore may benefit from early advanced therapies. To this end, prospective inception cohorts integrating medical records with multi-omics data are needed. The Belgian Prognostic biobANk of paTients witH Early cRohn’s or colitis (PANTHER) was therefore initiated in 2015. We here present the initial disease course of this cohort. Methods The PANTHER cohort is an inception cohort of adult IBD patients from 3 Belgian, tertiary IBD referral centres. Patients are included within 3 months after diagnosis, are naïve for immunosuppressives and biologicals, and without previous IBD-related surgery. Clinical data are prospectively collected; and DNA, serum, feces and intestinal biopsies are taken at predefined time points. Patients are treated according to routine clinical management. Log-rank tests, and univariate and multivariate analyses were performed in R 3.6.2. Results A total of 289 newly-diagnosed IBD patients were recruited (median [IQR] follow-up of 2.9 [1.4–4.2] years), of whom 161 (56%) had Crohn’s disease (CD), 122 (42%) had ulcerative colitis, and 6 (2%) had IBD type unclassified (Table 1). Thus far, 242 of these patients (83%) are minimally at 1-year follow-up. Twenty-two patients (9%) already needed surgery (n=5 for colectomy and n=17 for ileocecal or small bowel resection) and 124 patients (51%) received biological therapy within the 1st year after diagnosis. Time series analysis showed a clear trend for increase in biological use within the 1st year after diagnosis when comparing 2015–2017 (42%) to 2018–2020 (54%) (p=0.06) (Fig.1). Being exposed to a biological within the 1st year was associated with age (OR=0.98 [95%CI: 0.96–0.99]), CD diagnosis (OR=3.7 (95% CI: 2.2–6.3) and more recent diagnosis (2018–2020 as opposed to previous years) (OR=1.2 [95% CI: 1.2–3.4]). Within CD, perianal disease was the strongest driver for early biological use (OR=4.4 [95% CI: 1.8–12.8]). Early biological exposure led to clear trends in decreased surgery rates one year later (2/99 [2%]) as compared to non-exposed patients (8/108 [7%]) (p=0.07), while hospitalization rates significantly decreased (4% versus 12%, p=0.04). Conclusion In this Belgian inception cohort, an increase in early biological use is observed in recent years and is associated with reduced IBD-related surgery and -hospitalization.

Background Vedolizumab (VDZ), a gut-specific anti-integrin, is approved as a treatment for moderate to severe Crohn’s disease (CD) and ulcerative colitis (UC). Extra-intestinal manifestations (EIMs) are frequently associated with inflammatory bowel disease (IBD). However, the effect of VDZ on EIMs remains unknown. The aim of the current study was to describe the prevalence of EIMs in IBD patients at VDZ initiation, the evolution during continued treatment as well as the occurrence of new EIMs. Methods A single-centre study was performed in IBD patients who were started on VDZ between May 2010 and February 2019. Retrospectively, the physician-reported EIMs and intestinal disease activity (clinical and endoscopic) were assessed at baseline, 6 months and 1 year after the start of VDZ. Results The cohort consisted of 134 patients, including 77 CD patients, 56 UC patients and 1 patient with unclassified IBD. At VDZ initiation EIMs were assessed in 127 patients and 17.3% had ≥ 1 EIM: 9 hepatic EIMs (2 patients with toxic hepatitis, 2 with autoimmune hepatitis and 5 with PSC), 7 arthropathies (6 patients with axial spondyloarthropathy and 1 with peripheral arthritis), 3 non-further specified axial or peripheral arthralgias and 3 cutaneous EIMs (urticaria, psoriasis and erythema nodosum). Clinical evolution of the EIMs is reported in Table 1, assessment of intestinal disease activity in Table 2. During follow-up, 23 new EIMs were seen, mainly arthralgia, which was often transient. VDZ was stopped in 39/130 (30%) patients due to active intestinal disease in 32 patients, patients’ choice (n = 1) or because of deep disease remission (n = 1). In five patients, VDZ was stopped because of insufficient control of EIM. Conclusion A good clinical intestinal response was observed. However, the clinical evolution of EIMs appears unaffected by the use of VDZ in our cohort. Prospective data are needed to confirm these results.

Background Extra-intestinal manifestations (EIM) are frequently reported in inflammatory bowel diseases (IBD). Although the efficacy of TNF inhibitors is well documented, data regarding the effect of vedolizumab (VDZ) and ustekinumab (UST) are limited. Theoretically, the advantage of VDZ, i.e. gut-selectivity, may reduce the efficacy on EIM while the systemic effect of UST may be of benefit. Therefore, we evaluated the differences in new onset and evolution of EIM during both treatments. Methods An international multicentric retrospective study was performed on IBD patients who started VDZ or UST between May 2010 and December 2020. EIM were assessed at baseline and during follow-up. Arthropathy was defined as joint inflammation (arthritis/sacroiliitis) and arthralgia as articular pain without confirmed inflammation. Skin EIM included erythema nodosum (EN), pyoderma gangrenosum (PG) and Sweet syndrome. Ocular EIM included (epi)scleritis and uveitis. Uni- and multivariate analyses were performed. Results In total 856 patients were included: 528 treated with VDZ and 328 with UST. At baseline, arthropathy was more prevalent in UST treated patients (12.2% vs 7.2%; p=0.037; Table 1). No differences in rates of new onset (Fig 1) or evolution of pre-existing arthropathies could be identified between VDZ and UST. In multivariate analyses new onset arthropathy was not associated with smoking, IBD type, sex nor studied biological. In 5 out of 48 (10.4%) VDZ patients and 2 of 46 (4.3%) UST patients with either pre-existing or new arthropathy, treatment was stopped due to articular disease (difference not significant). In contrast, new arthralgia onset within 1 year of follow-up was significantly associated with VDZ treatment (OR 2.1 (1.1–4.0); p=0.022; Fig 1). Arthralgia was the reason to stop treatment in 2 of 87 (2.3%) VDZ patients and never in UST patients. Beside joint EIM, 2 patients developed EN, 1 PG and 1 episcleritis during VDZ treatment. Under UST treatment 1 patient developed EN. No patients developed new Sweet syndrome, scleritis nor uveitis. Conclusion No differences in the rate of new arthropathy onset were observed between VDZ and UST. In contrast, VDZ treatment did increase the risk of new onset arthralgia.