Complicated Crohn Research Articles

Long-Term Outcomes of Biological Therapy in Crohn's Disease Complicated With Internal Fistulizing Disease: BIOSCOPE Study From GETECCU.

The prevalence of penetrating complications in Crohn's disease (CD) increases progressively over time, but evidence on the medical treatment in this setting is limited. The aim of this study was to evaluate the effectiveness of biologic agents in CD complicated with internal fistulizing disease. Adult patients with CD-related fistulae who received at least 1 biologic agent for this condition from the prospectively maintained ENEIDA registry were included. Exclusion criteria involved those receiving biologics for perianal disease, enterocutaneous, rectovaginal, anastomotic, or peristomal fistulae. The primary end point was fistula-related surgery. Predictive factors associated with surgery and fistula closure were evaluated by multivariate logistic regression and survival analyses. A total of 760 patients from 53 hospitals (673 receiving anti-tumor necrosis factors, 69 ustekinumab, and 18 vedolizumab) were included. After a median follow-up of 56 months (interquartile range, 26-102 months), 240 patients required surgery, with surgery rates of 32%, 41%, and 24% among those under anti-tumor necrosis factor, vedolizumab, or ustekinumab, respectively. Fistula closure was observed in 24% of patients. Older patients, ileocolonic disease, entero-urinary fistulae, or an intestinal stricture distal to the origin of the fistula were associated with a higher risk of surgery, whereas nonsmokers and combination therapy with an immunomodulator reduced this risk. Biologic therapy is beneficial in approximately three-quarters of patients with fistulizing CD, achieving fistula closure in 24%. However, around one-third still undergo surgery due to refractory disease. Some patient- and lesion-related factors can identify patients who will obtain more benefit from these drugs.

Complicated Crohn’s disease: An unusual destination of an enterocutaneous fistula

Complicated Crohn’s disease: An unusual destination of an enterocutaneous fistula

Long-term home parenteral nutrition and profile of amino acids in serum and their loss in urine.

Amino acids are an essential part of parenteral nutrition. This study aimed to determine the serum profile of amino acids and their loss in urine in patients with long-term home parenteral nutrition (HPN) during 12 h of infusion in comparison with similar parameters in the remaining 12 h as well as in healthy participants. We enrolled forty-five patients with long-term HPN for 6-75 (median, 33) months. The indication for HPN was short bowel syndrome secondary to radical resection of the small intestine following complications of Crohn's disease. HPN was administered via two-chamber all-in-one bags prepared in a hospital pharmacy overnight for 12 h each day. The average dose of amino acids, carbohydrates and fats administered was 1·5, 3·4 and 0·68 g/kg per d, respectively, at an infusion rate of 0·11, 0·28 and 0·06 g/kg per h, respectively. The levels of essential amino acids in the serum of the patients were not significantly different from those in healthy individuals; however, of the non-essential amino acids, cystine and glutamine levels were lower and glycine and ornithine levels were higher in the patients (P < 0·05). Excretion of amino acids in the urine during 12 h of infusion at an infusion rate of 0·11 g/kg per h was 301 mg, while it was 104 mg during the remaining 12 h (P < 0·0001). Our patients on long-term HPN had a normal serum profile of essential amino acids. The total urinary excretion of amino acids during 12 h of infusion accounted for only 0·34 % (0·23-0·46) of the administered dose.

Laparoscopic surgery for complex Crohn's disease: perioperative and long-term results from a propensity matched cohort.

Laparoscopic surgery for complicated Crohn's (CD) is often technically challenging. Previous studies are limited by the comparison of heterogeneous cohortsof patients undergoing laparoscopic vs open surgery. We aimed to compare perioperative and long-term outcomes of matched patients undergoing laparoscopic and open colonic and ileocolonic resection. Primary outcomes were operative time, blood loss, and complications. Long-term outcomes were subsequent intraabdominal CD surgery, incisional hernia repair, and stoma reversal rates. Laparoscopic and open CD patients were 1:1 propensity score matched on age, body mass index, sex, indication, ASA grade, prior abdominal surgery, and postoperative Crohn's medication use based on the laparoscopic approach. A total of 906 patients underwent surgery for complex CD. After propensity matching, 386 were analyzed (193 open/193 lap, 51.3% male, mean age 33.9 + / - 12.6). Mean follow-up was 9.8 (range 7.9-12.1) years. Length of stay [(LOS) 6 (4, 8) vs 8 (5, 11) days, p < 0.001] and operative time [154 (110, 216) vs 176 (126, 239) min, p = 0.03] were shorter in the laparoscopic group. There was no difference in other complications or mortality. After adjusting for postoperative medications, no association was found between operative approach and subsequent intra-abdominal operation or incisional hernia repair. Laparoscopic patients were less likely to have postoperative sepsis [OR 0.40 (0.18, 0.91), p = 0.03]. In the setting of complicated Crohn's, in matched cohorts, laparoscopic surgery is associated with reduced operative times and LOS. Mortality, reoperation, and symptomatic hernia rates were equivalent to open surgery. Patients undergoing laparoscopic surgery are less likely to experience postoperative sepsis.

Endoscopic small bowel balloon dilations in patients with Crohn's disease: a Danish nationwide cohort study, 1997-2015.

Small bowel strictures are a common complication in Crohn's disease. Endoscopic balloon dilation (EBD) is an emerging therapeutic approach that is minimally invasive and helps to preserve the bowel. The aim of this study was to describe the use of EBD in adult Crohn's disease patients with small bowel strictures. This nationwide cohort comprised individuals ≥18 years old, diagnosed with Crohn's disease in Denmark between 1 January 1997 and 31 December 2015, according to the National Patient Registry (NPR). The cohort consisted of 9737 incident Crohn's disease patients that were followed for a median of 8.2 years [interquartile range (IQR) = 4.1-13.3]. During the observation period, a total of 90 (1%) patients underwent a small bowel-related EBD. After a follow-up period of a median of 3.4 (IQR = 1.8-5.0) years, primary small bowel strictures treated only with one dilation and no subsequent small bowel surgery accounted for 29 (59%) of 49 cases. A median of 7.2 (IQR = 2.4-13.2) months after their first dilation, 13 (27%) of those 49 patients underwent small bowel surgery. Forty-one patients with postsurgical strictures were dilated after a median of 6.5 (IQR = 2.5-10.2) years following small bowel surgery. Postsurgical strictures treated with only one dilation and no further small bowel surgery accounted for 20 (49%) of the 41 cases. The frequency of EBD in this Danish nationwide cohort was low. During a median follow-up of 5 years after EBD, most patients did not require further surgery. This suggests that EBD is an effective treatment and could be offered to more patients with Crohn's disease.

A comparative analysis and choice of surgical tactics in pediatric Crohn’s disease

Introduction. Currently, surgical complications in Crohn’s disease is still one of the most serious problems in pediatric surgery. An intensive development of video endoscopic surgery contributes to the active introduction of this technology in pediatric coloproctological practice. Crohn’s disease is still one of the most complex pathologies in pediatric gastroenterology, and surgical treatment of its complications is a disputable issue among pediatric surgeons. Up to now, there are no clear indications to surgery in the refractory form of Crohn’s disease, no standardized terms and types for surgical intervention, as well as no optimal variants of surgical access.Material and methods. A retrospective analysis of patients who had been treated surgically at departments of abdominal and emergency surgery in two pediatric hospitals in Moscow (Morozovskaya and Izmailovskaya ) was carried out. 39 children with Crohn’s disease, aged 4–17 year, were included in the study. All patients had standard clinical examination: clinical examination with anamnesis, laboratory and instrumental diagnostics.Results. The obtained results have shown that laparoscopic interventions have a number of advantages, such as less traumatic surgery, reduced exposure to anesthesia and shorter intestinal stimulation, less stay in ICU, shorter hospitalization as well as more rapid rehabilitation period.Conclusion. The performed assessment of outcomes after surgical treatment of children with complicated Crohn’s disease helped to develop indications for the selection of surgical technique in the ileocecal form. Thus, the obtained results improved outcomes in children with complicated Crohn’s disease because of the outlined indications for surgery and surgical tactics when minimally invasive techniques are more preferable.

Early versus delayed ileocolic resection for complicated Crohn's disease?

Early versus delayed ileocolic resection for complicated Crohn's disease?

Real clinical practice of complicated Crohn’s disease treatment with ustekinumab: clinical case presentation

Crohn’s disease (CD) is a severe immune-mediated disease with segmental transmural inflammation and ulcers in gastrointestinal tract most often in terminal ileum and colon. The disease is often associated with severe complications such as fistulas and strictures that require aggressive treatment or surgery. CD treatment remains the unresolved and one of the most serious problems in gastroenterology. Glucocorticosteroids (GCS) are the essential treatment options for many years but unfortunately the frequency of steroid resistance and steroid dependence are constantly increasing. In the cases of steroid refractory CD treatment options include biologics of different classes: tumour necrosis factor alfa - inhibitors (iTNF-α), α4β7 integrin inhibitor (vedolizumab), IL-12/23 inhibitor (ustekinumab). Any of these drugs can be used in bio-naïve CD patients, however secondary loss of response was noted for all biologics over time.In the cases of the first line treatment failure the problem of correct choice of the second and subsequent lines of biologics appears, since some biologics may show lower efficacy in the second line of treatment. Real clinical practice will allow us to make a more correct choice of next biologic. Ustekinumab, a human interleukin -12/23 monoclonal antibody is one of biologics that is highly effective in the first-line CD therapy and remains effective in the subsequent lines of treatment. We present a clinical case of complicated CD in young female with negative disease prognosis and loss of response to three iTNF-α. In this case the high efficacy of ustekinumab after multiple iTNF-α failure was demonstrated.

A systematic review and functional bioinformatics analysis of genes associated with Crohn\u2019s disease identify more than 120 related genes

BackgroundCrohn’s disease is one of the two categories of inflammatory bowel diseases that affect the gastrointestinal tract. The heritability estimate has been reported to be 0.75. Several genes linked to Crohn’s disease risk have been identified using a plethora of strategies such as linkage-based studies, candidate gene association studies, and lately through genome-wide association studies (GWAS). Nevertheless, to our knowledge, a compendium of all the genes that have been associated with CD is lacking.MethodsWe conducted functional analyses of a gene set generated from a systematic review where genes potentially related to CD found in the literature were analyzed and classified depending on the genetic evidence reported and putative biological function. For this, we retrieved and analyzed 2496 abstracts comprising 1067 human genes plus 22 publications regarding 133 genes from GWAS Catalog. Then, each gene was curated and categorized according to the type of evidence associated with Crohn’s disease.ResultsWe identified 126 genes associated with Crohn’s disease risk by specific experiments. Additionally, 71 genes were recognized associated through GWAS alone, 18 to treatment response, 41 to disease complications, and 81 to related diseases. Bioinformatic analysis of the 126 genes supports their importance in Crohn’s disease and highlights genes associated with specific aspects such as symptoms, drugs, and comorbidities. Importantly, most genes were not included in commercial genetic panels suggesting that Crohn’s disease is genetically underdiagnosed.ConclusionsWe identified a total of 126 genes from PubMed and 71 from GWAS that showed evidence of association to diagnosis, 18 to treatment response, and 41 to disease complications in Crohn’s disease. This prioritized gene catalog can be explored at http://victortrevino.bioinformatics.mx/CrohnDisease.

Profuse haematochezia related to Crohn’s disease: a rare case report

Background: Lower gastrointestinal bleeding (LGIB) can be caused by irritable bowel disease. Haematochezia is one of the LGIB symptoms. Profuse haematochezia is a rare complication in Crohn’s disease. Case Presentation: We reported a 24-year-old patient with profuse haematochezia with severe anaemia and hypovolemic shock. Anamnesis, physical examination and colonoscopy showed that haematochezia was caused by Crohn’s disease. Colonoscopy was done after the patient was hemodynamically stable with findings of external haemorrhoid and multiple ulcers with varying size (0.5–2 cm) on ascending colon, caecum and terminal ileum. The tissue histopathology of ileocecal junction indicated intestinal epithelia with partially eroded, crypts infiltrated by inflammatory cells, swollen lamina propria with proliferation and dilation of blood vessels indicting the Crohn’s disease. The patient then treated with Crohn’s disease medical therapy including low dose oral steroid, sulfasalazine and antibiotics. Clinical improvement was found on one week follow-up after discharge from hospital. Conclusion: Profuse haematochezia could be associated with Crohn’s disease and the comprehensive approaches should be taken to manage the Crohn’s disease with such presentation.

Interleukin-26 Expression in Inflammatory Bowel Disease and Its Immunoregulatory Effects on Macrophages.

Background and AimInterleukin-26 (IL-26) has been implicated in several chronic inflammatory diseases. However, its role in inflammatory bowel disease (IBD) remains to be elucidated. We aimed to investigate IL-26 expression in IBD and its immunoregulatory effects on macrophages.MethodsWe assessed IL-26 expression in the intestinal mucosa and blood samples of IBD patients and healthy controls (HC). The associations between the clinical characteristics of IBD and IL-26 expression levels in serum and peripheral blood mononuclear cells (PBMCs) were investigated. In addition, the transcriptional changes in THP-1 macrophages exposed to IL-26 were determined by RNA sequencing and validated with qRT-PCR, ELISA and western blots.ResultsCompared with HC, in IBD patients, IL-26 expression levels were elevated in the inflamed intestinal mucosa, and reduced in serum and PBMCs. IL-26 mRNA levels in PBMCs, but not serum IL-26 levels, were inversely correlated with disease activity in IBD. Furthermore, IL-26 mRNA levels in PBMCs were significantly lower in patients with complicated Crohn’s disease. A total of 1,303 differentially expressed protein-coding genes were identified between untreated and IL-26-treated macrophages. The up-regulated genes showed enrichment in some inflammatory and immune-related processes and pathways. Additionally, GSEA showed that neutrophil, monocyte, and lymphocyte chemotaxis was significantly enriched in IL-26-treated macrophages. Further validation revealed that IL-26 promotes the secretion of multiple inflammatory cytokines and chemokines and upregulates the expression of adhesion molecules, MMP-8, and MMP-9 while inhibiting MMP-1 in macrophages.ConclusionCompared with HC, in IBD patients, IL-26 levels were elevated in the inflamed intestinal mucosa, and reduced in the peripheral blood. The transcriptional changes in macrophages exposed to IL-26 suggest that IL-26 may amplify the aberrant immune response in IBD by activating macrophages.

Perioperative outcomes of minimally invasive ileocolic resection for complicated Crohn disease: Results from a referral center retrospective cohort

BackgroundMinimally invasive ileocolic resection for complicated Crohn disease, defined as penetrating Crohn disease associated with intra-abdominal fistula, abscess, or phlegmon, is challenging. In addition, the impact of the minimally invasive approach on postoperative outcomes is still debated. This study aimed to compare the intraoperative and postoperative outcomes of minimally invasive ileocolic resection for complicated versus uncomplicated Crohn disease. MethodsA retrospective analysis of all consecutive adult patients with Crohn disease undergoing minimally invasive ileocolic resection from 2014 to 2021 was performed. Perioperative outcomes were compared between patients with complicated Crohn disease (complicated group) and patients without these lesions (uncomplicated group). ResultsAmong the 274 patients undergoing minimally invasive ileocolic resection for Crohn disease, 101 (36.9%) had a robotic approach, and 84 (30.7%) had complicated Crohn disease. Complicated patients were more frequently malnourished (32.1% vs 16.1%, P = .004) and had more frequent previous bowel resections for Crohn disease (22.1% vs 9.5%, P = .002). There were no differences between both groups regarding intraoperative complications (1.1% uncomplicated group vs 2.4% complicated group, P = .463), conversion rate (2.6% uncomplicated group vs 4.8% complicated group, P = .463), postoperative morbidity (27.4% uncomplicated group vs 34.5% complicated group, P = .231), intra-abdominal septic complications (4.2% uncomplicated group vs 7.1% complicated group, P = .309), and length of stay (3.8 ± 2.0 days uncomplicated group vs 4.2 ± 3.0 complicated group, P = .188). ConclusionMinimally invasive ileocolic resection for complicated Crohn disease is safe and feasible. Future prospective studies are needed to confirm these results.

Neutrophil-to-Lymphocyte Ratio is a Useful Biomarker for Predicting Postoperative Complications in Crohn’s Disease

Neutrophil-to-Lymphocyte Ratio is a Useful Biomarker for Predicting Postoperative Complications in Crohn’s Disease

Ultrasonography in inflammatory bowel disease - So far we are?

Intestinal ultrasound (IUS) is a non‐invasive and accurate tool to assess inflammatory bowel disease. The ECCO‐ESGAR guideline recommends the use of IUS for the assessment of disease activity and complications in Crohn's disease (CD). In addition, an increasing body of evidence suggests the use of IUS as alternative to colonoscopy in monitoring CD and in assessing disease activity of ulcerative colitis. Early responsiveness of IUS findings by the first weeks of treatment and the advantage to perform the procedure in real time may dramatically change frequency of the assessment of treatment response in the future and speed up the clinical decision‐making process. Development of validated and reproducible sonographic scores to measure disease activity and therapeutic response and spread of knowledge of IUS remain relevant issues for the future in which current researchers and the International Bowel Ultrasound (IBUS) Group are actively engaged.

Efficacy and tolerability of hyperbaric oxygen therapy in small bowel stricturing Crohn's disease: a pilot study.

Background/AimsExisting therapeutic options for complicated Crohn’s disease (CD) like biologics and surgery are limited by inadequate long-term efficacy, cost, and adverse effects. Tissue hypoxia is important in CD pathogenesis and may be ameliorated with hyperbaric oxygen therapy (HBOT). We assessed the efficacy and tolerability of HBOT in small bowel stricturing CD.MethodsThis pilot study included patients of small bowel stricturing CD (from April 2019 to January 2020) who underwent HBOT. These patients were refractory to conventional medical treatment or had multiple strictures not amenable to resection. Each session of HBOT was given for 60 minutes with a pressure of 1.5–2.5 atm. Clinical, biochemical responses and Short Inflammatory Bowel Disease (SIBD) questionnaire were evaluated at 2 and 6 months, and radiological response was evaluated at 6 months.ResultsFourteen patients (mean age, 42.9±15.7 years; male, 50%) were subjected to 168 HBOT sessions. Thirteen patients (92.7%) had strictures and 1 patient had enterocutaneous fistula in addition. Median number of HBOT sessions was 11 (range, 3–20) which were administered over a median of 4 weeks. Most patients tolerated it well except 1 who had hemotympanum. At 2 and 6 months of follow-up, 64.2% of patients had a clinical response, 50% and 64.2% of patients had clinical remission respectively. Steroid-free clinical remission was seen in 8 (57%) of patients with radiological improvement in 50%. There was a significant improvement in SIBD scores at 2-month follow-up (59.4 vs. 44.5, P=0.03).ConclusionsHBOT can be a safe and effective therapeutic option in patients with stricturing small bowel CD refractory to conventional medical treatment.

TH17 CELLS PROMOTE INTESTINAL FIBROSIS THROUGH THE PRODUCTION OF AMPHIREGULIN

Abstract BACKGROUND &amp; AIMS Intestinal fibrosis is a major serious complication of Crohn’s disease (CD). Gut microbiota-reactive Th17 cells have been established as crucial in the pathogenesis of CD, however, how Th17 cells induce fibrosis is still not completely understood. METHODS Wild-type Th1 cells and Th17 cells, or amphiregulin (Areg)-/- Th17 cells, were transferred into Tcrbxd-/- mice to induce colitis and intestinal fibrosis. CD4+ T cell expression of Areg was determined by qRT-PCR and ELISA. Intestinal fibroblasts were isolated from normal and CD patients and used to determine the effects of Areg on cell proliferation and migration in vitro. Video microscopy and single-cell tracking were used to assess cell migration kinetically. Areg expression was compared in peripheral blood CD4+ T cells, intestinal biopsy tissues, and lamina propria lymphocyte (LPL) from healthy controls and CD patients with or without intestinal fibrosis. RESULTS When transferred into TCRβ/δ-/- mice, although Th1 and Th17 cells induced intestinal inflammation at similar levels, Th17 cells induced more severe intestinal fibrosis than Th1 cells. RNA-seq analysis showed higher levels of AREG expression in Th17 cells compared to Th1 cells, which was further confirmed by qRT-PCR. Transfer of Areg-/- Th17 cells induced less severe fibrosis in TCRβ/δ-/- mice compared with WT Th17 cells. IL-6 but not IL-23 promoted Areg expression in Th17 cells in a time and dose-dependent manner. Treatment with Th17 signature cytokine IL-21, but not IL-17, upregulated T cell expression of Areg. Consistently, IL-21R-/- T cells produced lower levels of Areg. Mechanically, STAT3 mediates Areg expression in Th17 cells, in that IL-6 promoted STAT3 activation, and IL-6 did not induce AREG expression in STAT3-/- T cells. Areg expression was lower in STAT3-/- T cells compared with WT T cells under Th17 conditions. Treatment with RORgt inhibitor, which inhibits Th17 differentiation, suppressed Th17 cell Areg expression, indicating that higher Areg expression requires fully Th17 differentiation. Areg promoted human intestinal fibroblast proliferation and motility, which was mediated by activation of mTOR, and mTOR inhibitors inhibited Areg-induced human intestinal fibroblast proliferation and motility. Finally, Areg expression is increased in peripheral blood CD4+ T cells, intestinal biopsy tissues, and lamina propria lymphocytes of CD patients with fibrosis. CONCLUSION Collectively, these findings reveal that Th17-derived Areg promotes fibrotic responses in both experimental colitis and human CD patients. Thereby, Areg could serve as a potential therapeutic target for fibrosis in CD.

P100 Serum inflammatory protein profiling to corroborate selection of therapy naïve moderate-to-severe pediatric Crohn’s disease patients eligible for first-line infliximab treatment

Abstract Background Early intervention with biologic therapy, especially with anti-Tumor Necrosis Factor-a, is very effective and now more commonly used to prevent disease progression and complications in Crohn’s disease (CD). However, a rational approach to decide which patient should be treated First-line Infliximab (FL-IFX) is lacking. In this study, using serum from a randomized control trial, we assessed how changes in immune profiles prior to therapy and after the first standardized induction treatment with either FL-IFX or conventional treatment (CONV) related to maintaining disease remission at week 52. Methods Serum samples from therapy naive moderate to severe CD patients from the TISKIDS study1 were used at time of diagnosis and at 10–14 weeks after induction therapy with FL-IFX (n=48) and CONV (n=43). FL-IFX consisted of 5 IFX infusions (5 mg/kg) combined with azathioprine (AZA) maintenance. CONV consisted of induction therapy with Exclusive Enteral Nutrition or oral prednisolone combined with AZA maintenance. Concentrations of 92 inflammatory proteins were determined with Olink Proteomics®. Significant differences in mean protein NPX after FDR adjustment with log2fold &amp;gt; 0.5 were considered meaningful. Results After 10–14 weeks of induction therapy, FL-IFX suppressed a larger number inflammatory proteins and induced stronger suppression compared to CONV. Of the 30 significantly modulated FL-IFX target proteins 18 were differentially regulated by FL-IFX only. Hierarchical clustering of patients based on their baseline profiles of the 30 IFX-modulated proteins revealed 2 patient clusters, a CD-hi cluster with significantly higher baseline clinical disease activity, CRP and blood neutrophil concentrations compared to the CD-lo cluster. The CD-hi cluster had an increased abundance of 23/30 proteins amongst which Oncostatin-M, TNFSF14, HGF and TGF-alpha compared to the CD-lo cluster (Figure 1A). Of the CD-lo patients treated with FL-IFX, 58% reached clinical disease remission without treatment escalation at week 52, while this was only 24% for CD-hi patients treated with FL-IFX. Only 20% of the CD-lo patients treated with CONV reached remission while this was only 6% for the CONV treated patients in the CD-hi group (Figure 1B). Strikingly, similar clustering using the immune profiles after 10–14 weeks induction therapy did not predict remission at week 52. Conclusion FL-IFX achieves stronger reduction and modulates more inflammatory serum immune protein concentrations than CONV. Stratification of patients according to profiles of IFX-modulated proteins prior to therapy identifies patients with a lower chance of reaching clinical remission without treatment escalation at week 52. Reference 1. Jongsma MME et al. Gut. 2020 Dec; DOI:10.1136/ PMID:33384335

P201 Crohn’s Disease of the terminal ileum associated with ileo-sigmoid fistula: risk factors for ileostomy formation and postoperative complications during the years of biologics

Abstract Background Ileo-sigmoid fistula (ISF) is a complication of Crohn’s disease occurring in a significant proportion of patients. The aim of this study was to describe the perioperative outcomes of patients affected by ISF and to identify the risk factors for complications and ileostomy formation. Methods Consecutive patients operated for ISF between 2004 and 2021 in a single referral centre were included. Considering the presence of a large number of regressors the variables to include in the models were selected using the least absolute shrinkage and selection operator (LASSO) method. The multivariate analyses of the independent variables associated with the risk of ileostomy formation and post-operative complications were conducted using logistic regression. Results Of the 208 patients who underwent ileocolic resection for ISF (Table 1), 161 (77.4%) also underwent sigmoid resection, while 47 (22.6%) underwent a conservative treatment of the target sigmoid colon. ISF was detected preoperatively with CT scan in 121 (58%) patients and with colonoscopy in 63 (30%) patients. Significant risk factors for ileostomy (performed in 63 patients - 30%, Table 2) were the preoperative diagnosis of ISF (Odds Ratio - OR - 2.22, 95% Confidence Interval - CI – 1.02–4.78), surgery for a recurrence (OR 6.71, 95% CI 1.46–30.86), the presence of an intrabdominal abscess (OR 3.03, 95% CI 1.44–6.35), and additional small bowel surgery (OR 2.6, 95% CI 1.08–6.25). Anastomotic leak occurred in 19 (9%) patients. Postoperative complications classified grade 2 or higher according to Clavien-Dindo (71 patients, 34.1%) were significantly associated with additional small bowel surgery (OR 2.42, 95% CI 1.11–5.3), the presence of an intrabdominal abscess (OR 2.45, 95%CI 1.44–6.35), and the localization of Crohn’s disease to the left colon (OR 1.98, 95%CI 1.03–3.8). Conclusion Although a diverting ileostomy was more likely to be performed in those patients identified perioperatively as high-risk subjects (more clinically relevant ISF, recurrent disease, addition bowel surgery or abdominal sepsis), this did not prevent the onset of postoperative complications, which seem to be associated with a more disseminated disease (either to the colon or to other locations of the small bowel) or with the presence of untreated intra-abdominal sepsis.

P315 High symptom burden and impact on health-related quality of life in patients with Crohn’s perianal fistulas: results from a global burden of illness study

Abstract Background Perianal fistulas (PAF) are a common complication in Crohn’s disease (CD) and can be associated with an increased burden of illness. A global study was conducted to assess the burden of illness in patients with Crohn’s perianal fistulas (CPF) compared with patients with CD without PAF (non-PAF CD). Here we present patient symptom burden and impact on HRQoL. Methods This cross-sectional study was conducted in seven countries (France, Germany, Spain, UK, Canada, Australia and Japan) in patients aged ≥21 and ≤90 years with self-reported physician-diagnosed CD. Patients were classified as having non-PAF CD (cohort, 1) or CPF without PAF-related surgery (cohort, 2) or CPF with PAF-related surgery (cohort, 3). Customised questions and validated general and disease-specific patient-reported outcome data were collected via a, 45-min IRB/EC-approved web-enabled questionnaire. Symptom burden and impact on HRQoL were evaluated using the Short Inflammatory Bowel Disease Questionnaire (SIBDQ, scores, 1–7 [low–optimum] with, 2-week recall period) in all cohorts and Quality of Life in Patients with Anal Fistula (QoLAF, scores, 14–70 [low–high impact]) in cohorts, 2 and, 3. Data were analysed using descriptive statistics. Results Of, 929 patients recruited (cohort, 1, n=620; cohort, 2, n=174; cohort, 3, n=135), 58–69% were male and, 55–67% were aged, 21–40 years across all cohorts. Cohorts, 2 and, 3 experienced a significantly higher frequency of CD-related complications than cohort, 1 (mean [standard deviation, SD]:, 9.4 [4.5] and, 11.1 [5.2] vs, 6.0 [4.1], respectively; both p &amp;lt;0.05, Table, 1) and had a higher number of CD-related surgeries (other than PAF-related surgeries) in the past, 12 months (mean [SD]:, 1.8 [1.1], p =0.109 and, 2.2 [1.3], p &amp;lt;0.0001 vs, 1.5 [0.9], respectively). In patients with CPF, a smaller proportion in cohort, 2 had active PAF vs cohort, 3 (136 [78%] vs, 119 [88%], respectively; p =0.022) and a smaller proportion had experience with post-treatment PAF recurrence/persistence in cohort, 2 vs cohort, 3 (84 [48%] vs, 80 [59%], respectively; p =0.055). Overall SIBDQ scores were significantly lower (worse) in cohorts, 2 and, 3 than in cohort, 1 (3.8 and, 3.7 vs, 4.1 respectively; both p &amp;lt;0.001). In patients with CPF, total QoLAF scores were comparable between cohorts, 2 and, 3 (41 and, 42, respectively), although patients in cohort, 3 had a significantly higher (worse) score in the physical impact domain compared with cohort, 2 (21 vs, 19, respectively; p &amp;lt;0.05). Conclusion In this large global study, we observed that patients with CPF had incrementally higher symptom burden, owing to both CD and PAF, compared with patients with non-PAF CD. For patients with CPF, there was no difference in HRQoL irrespective of whether they had received PAF-related surgery or not.

P094 Transcriptomic and small RNA sequencing profile in ileal resections from complicated Crohn′s Disease patients

Abstract Background Crohn′s disease is a chronic inflammatory disorder of gastrointestinal tract that is classified into three different behaviours: the inflammatory (B1), the stenotic (B2) or the penetrating (B3). We pretend to identify differences in transcriptomic and non-long coding RNA expression profiles associated to damaged and no-damaged surgical ileal resections from complicated CD patients. Methods We conducted both RNA and small RNA sequencing profiling on ileal surgical resections from CD patients with structuring (n=10) or penetrating (n=10) behaviour; from each patient we obtained a sample from affected tissue (B2A and B3A, respectively) and the paired non-affected ileum (B2C and B3C, respectively). Ten ileal resections (control samples) were obtained from non-affected ileum of patients with right colorectal cancer (IL). Enrichment scores of the GO terms and KEGG pathways were used to functional analysis investigated in this study. Gene expression and miRNA profiles were validated by RT-qPCR. Results Our comparative bioinformatic analysis of RNA sequencing showed that the comparation of IL and the non-affected ileum from CD patients (B2C+B3C) revealed that only 11 genes were significantly altered and any miRNA with significative expression. The comparative analysis between B2A+B3A vs B2C+B3C showed: a) 2562 genes differentially regulated and the GO enrichment analysis determined that inflammation, cell activation, and regulation of the extracellular matrix (EM) were the main biological processes altered (Figure 1a). KEGG analysis showed that cytokine-receptor interaction and MAPK and Ras signalling were the most affected pathways (Figure 1b). Among the top ten up-regulated genes we found several immunoglobulins (such as IGHG4, IGHG3, and IGHG1), proteins of the extracellular matrix EM (such as EPYC, COMP, and CHI3L1), and transcription factors (such as PRRX1). When the analysis was performed by CD behaviour, results revealed that most of these genes were significantly increased in both, B2 and B3 CD; b) 103 miRNAs with differential expression, 56 were up-regulated and 47 were down-regulated. Negative and significant correlations were detected between the RNA expression of ECM components and some miRNA expression. Figure 1. Bar plot of enrichment analysis with differential expressed genes between B2A+B3A vs B2C+B3C. A) Biological Process (BP), Cellular Component (CC), and Molecular Function (MF) of Gene Ontology (GO) enrichment analysis. B) Enrichment of Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Conclusion The correlation detected between extracellular matrix components and some miRNA suggest an epigenetic regulation in the affected ileum of complicated CD patients.