Surgical and non-surgical risk factors affecting the insufficiency of ileocolic anastomosis after first-time surgery in Crohn's disease patients.

P070 - The role of preoperative optimalisation before surgery in IBD patients

There is evidence that, in Crohn's disease (CD), lamina propria T lymphocytes (LPLs) are resistant to FAS-mediated apoptosis and that this defect contributes to the mucosal T-cell accumulation. In this study we examined the functional role of Flip, a Flice inhibitor protein, in the resistance of CD LPL to FAS-mediated apoptosis. Biopsy specimens and LPLs were taken from CD and ulcerative colitis (UC) patients and normal controls and analyzed for Flip by Western blotting. We also examined whether inhibition of Flip by antisense oligonucleotide restored the susceptibility of CD LPLs to FAS-induced apoptosis. LPL apoptosis was assessed by flow cytometry. After FAS stimulation, the rate of apoptosis of CD3+ LPLs was higher in normal controls and patients with UC than in patients with CD. Enhanced expression of both long and short Flip isoforms was seen in biopsy specimens and purified CD3+ and CD45RO+ LPLs of CD patients in comparison with UC patients and normal controls. No increase in Flip was documented in untreated celiac disease mucosa, thus suggesting the possibility that induction of Flip in the gut does not simply rely on the ongoing inflammation. Finally, we showed that inhibition of Flip by antisense oligonucleotide reverted the resistance of CD LPLs to FAS-induced apoptosis. Data suggest a role for Flip in the resistance of CD LPLs to FAS-mediated apoptosis.

IntroductionIntestinal failure (IF) is a rare but serious complication of Crohn’s disease (CD). However, to date, surgical risk factors remain poorly characterised and data from individual studies can be difficult...

FECAL MICROBIOTA OF PEOPLE WITH CROHN'S DISEASE DOES NOT CHANGE WITH ILEOCECAL RESECTION

INTRODUCTION Up to 80% of people with ileal Crohn’s disease (CD) will require an ileocecal resection (ICR). CD recurrence following surgery is common, although antibiotics can reduce short term recurrence rates. Following an ICR, it is unknown what happens to the fecal microbiota and how the microbiota relates to CD recurrence. To further investigate this, we analyzed fecal microbiomes of patients with CD (with and without an ICR) and compared to healthy controls. HYPOTHESIS Patients with CD and active inflammation have more dysbiosis of their fecal microbiomes, and ileocolonic resection (ICR) improves this dysbiosis. METHODS We performed a cross sectional study of fecal samples patients with CD (stratified by ICR status) and healthy controls. DNA was isolated and the V4 hypervariable region of the 16S rRNA gene was amplified and sequenced using the Illumina platform. Ecological metrics were applied to characterize fecal microbiomes. In our comparison, CD patients were further stratified based on their most recent colonoscopy into the following groups: 1) history of ICR versus surgically naïve CD patients, 2) active inflammation (in either the ileum and/or colon), and 3) active ileal inflammation versus none (colonic inflammation excluded). RESULTS Twenty-four CD patients (n=14, 58 % with ICR) and 38 healthy controls provided fecal samples. Global trends demonstrated that CD patients have significantly reduced richness (or observed taxonomic units) (Figure 1 A, p<0.0001) and significantly reduced Shannon diversity indices (Figure 1 B, p<0.0001) in their fecal microbiomes compared to healthy controls. Community diversity based on principal component analysis of Bray-Curtis pairwise dissimilarity indices is shows distinct clustering between healthy controls and CD patients (Figure 1 C). Richness and Shannon diversity index is not significantly different between CD patients that are surgically naïve compared with those that have undergone ICR (Figure 2 A and B). Richness and Shannon diversity indices are not significantly different between CD patients without versus with active inflammation (Figure 2 C and D) and is also not significant in CD patients without vs with ileal inflammation (Figure 2 E and F). CONCLUSION CD is characterized by fecal microbiota dysbiosis. ICR did not impact the fecal microbiota and fecal samples could not distinguish ileal inflammation. ICR paired with therapies to improve dysbiosis may affect CD recurrence.

Background The microbiota most likely has an essential role in the pathogenesis of Crohn’s disease (CD). While faecal diversion after ileocecal resection (ICR) protects against CD recurrence, re-exposure triggers inflammation. After ICR, the majority of patients develop recurrence in the neoterminal ileum and the ileal microbiome is of particular interest. We have therefore assessed the mucosa-associated bacterial microbiome in the inflamed and non-inflamed ileum of patients with CD. Methods Patients with an established diagnosis of CD undergoing ileocolonoscopy and healthy controls (HC) referred for colonoscopy due to rectal bleeding or screening for disease, but without any detected gastrointestinal pathology were invited to participate. Exclusion criteria included use of antibiotic treatment for the past 2 months. Mucosal pinch biopsies were sampled 5 cm and 15 cm orally of the ileocecal valve or ileocolic anastomosis for comparisons within the same patients. The biopsies were analysed by 16S rRNA sequencing, α- and β-diversity was assessed by Shannon entropy and Bray-Curtis dissimilarity index respectively. Histologic inflammation was graded. Results Fifty-one CD patients, where of 32 with previous ICR, and 40 HC were included in the study. Of the 51 CD patients, 20 had terminal ileitis, with endoscopically inflamed mucosa at 5 cm and normal appearing mucosa at 15 cm and no history of upper GI disease involvement. Seven CD patients had ileal stenosis. CD patients (n = 51) had lower α-diversity and separated clearly from HC on β-diversity plots (Figure 1). Twenty-three bacterial taxa were differentially represented in CD patients and HC, among these Tyzzerella 4 was found to be profoundly overrepresented in CD (p = 4.1 × 10–68). When comparing the microbiome in the inflamed ileal mucosa with the proximal non-inflamed mucosa within CD patients (n = 20) neither α- or β-diversity differed (Figure 2). Furthermore, no bacterial taxa were differentially represented in the inflamed vs. proximally non-inflamed mucosa. CD patients operated with ICR had lower α-diversity (p = 0.021), but β-diversity did not differ from CD patients without ICR. CD patients with stenosis had lower abundances of Bacteroides, Sutterella and Akkermansia species. Conclusion 23 taxa were differentially expressed in CD compared with HC. The ileal mucosa-associated microbiome is similar assessed by both α- and β-diversity in the inflamed mucosa and the proximal non-inflamed mucosa within the same patients. Our results support the concept of CD specific microbiota alterations and demonstrate that neither ileal sub-location nor endoscopic inflammation itself influence the mucosa-associated microbiome.

Background: Terminal ileum inflammation and surgical resections impair absorption of vitamin B12 and D in patients with Crohn’s disease (CD) and Ulcerative Colitis (UC). We assessed differences in subclinical deficiencies of vitamin B12 (<350 pg/mL) or D (<50 nmol/L), by lesion localization (namely non-ileal CD, ileal CD, and UC) and surgical resection status (namely no resection, non-ileal small bowel resections, ileocecal resections, and colonic resections) in CD and UC patients. Methods: We analyzed data from 571 patients (17–93 years), with UC (51%) and CD (49%, including 47 non-ileal (8%), 244 ileal-CD (46%)) managed at the University of Missouri Health Care System (Jan 2017–April 2022). Results: Prevalence of vitamin B12 and vitamin D deficiencies was 19% and 83%, respectively. Prevalence of resection was 26%, including 5% with non-ileal small bowel resections, 11% with ileocecal resections, and 10% with colonic resections. CD with ileal involvement was associated with a 3-fold elevated risk of B12 deficiency (p = 0.004), but not vitamin D. Ileocecal resections were associated with a >3-fold increase in both B12 deficiency (OR = 3.53, p = 0.001) and D deficiency (OR = 3.35, p = 0.044). Conclusions: CD patients with ileal involvement and ileocecal resections have an elevated risk of vitamin B12 and D deficiency, and may benefit from adjunctive supplementation.

Objective The purpose of this analysis was to describe pain medication utilization of newly diagnosed patients with Crohn’s disease (CD) and ulcerative colitis (UC) over 12-months before and after initiation of a biologic. Methods This is a retrospective study using administrative claims from the HealthCore Integrated Research Database. Patients newly diagnosed with CD or UC who initiated a biologic from 1/1/2014 to 7/31/2017 were included. Medications that could be used for pain control were assessed 12-months prior and 12-months after biologic initiation. Demographics, baseline clinical characteristics, and pain medication use were described using descriptive statistics. Frequencies and percentages were provided for categorical variables and means, standard deviations, and medians were presented for continuous measures. The differences in pain medication use 12 months prior and 12 months after biologic initiation were assessed using McNemar’s Test for categorical variables and Wilcoxon signed-rank test for continuous variables.. Results 540 CD patients and 373 UC patients were included in this analysis. CD patients had a mean age of 36.8 years, 50.0% were female, and the mean time from diagnosis to biologic initiation was 7.1 months. UC patients had a mean age of 39.9 years, 44.0% were female, and the mean time from diagnosis to biologic initiation was 10.9 months. Prior to biologic initiation, 23.1% of CD patients were prescribed NSAIDs, 78.1% glucocorticoids, 49.4% opioids, and 29.3% neuromodulators. Similarly, prior to biologic initiation, 20.9% of UC patients were receiving NSAIDs, 91.4% glucocorticoids, 40.8% opioids, and 29.5% neuromodulators. Twelve months after biologic initiation, use of NSAIDs (CD: 23.1% vs. 15.0%; UC: 20.9% vs. 15.8%) and glucocorticoids (CD: 78.1% vs. 58.9%; UC: 91.4% vs. 74.3%) significantly decreased among CD and UC patients. Opioid use decreased among UC and CD patients; however this decrease was only statistically significant for CD patients (CD: 49.4% vs. 41.5%; UC: 40.8% vs. 36.5%). Use of neuromodulators significantly increased during 12-months after biologic initiation compared to 12 months prior to initiation among CD (29.3% vs. 33.7%) and UC (29.5% vs. 35.7%) patients. Conclusion Use of pain medications such as NSAIDs, glucocorticoids, opioids, and neuromodulators were common among CD and UC patients. Though rates of NSAIDs and glucocorticoids decreased after the initiation of biologics, 59% of CD and 74% of UC patients were still receiving glucocorticoids, and 15% of CD and 16% of UC patients were still receiving NSAIDs 12-months after initiation of a biologic. In addition, 42% of CD and 37% UC patients were still receiving opioids 12-months after initiation of a biologic. The results suggested that CD and UC patients are still receiving pain medication even after initiating biologics.

Interleukin-21 enhances T-helper cell type I signaling and interferon-γ production in Crohn’s disease

Crohn disease (CD) is a chronic inflammatory bowel disease that affects the entire gastrointestinal tract. The standard treatment for CD is medication to control the inflammation and relieve the symptoms. CD patients often require surgery at some point in their life for complications, treatment resistance, and side effects of medication. However, postoperative recurrences are common. To reduce anastomotic troubles, several types of anastomosis were investigated. Kono-S anastomosis, an antimesenteric, functional, end-to-end handsewn anastomosis, was introduced in order to prevent the restenosis caused by recurrence of CD in 2010. Kono-S anastomosis is expected lower susceptibility to mechanical distortions due to the stability provided by the “supporting column.” We herein report 2 cases of CD performed with a Kono-S anastomosis. The importance of these cases is that Kono-S anastomosis is useful for preventing restenosis caused by recurrence. The first patient was a 26-year-old man who suffered from CD for 9 years. Computed tomography (CT) showed inflammation and stenosis at the ileocecum, a fistula between the terminal ileum and sigmoid colon, and an intraperitoneal abscess. We performed an ileocecal resection and a Kono-S anastomosis. The second patient was a 25-year-old woman who suffered from CD for 8 years. CT showed inflammation and stenosis at the ileocecum, and a retroperitoneal abscess. We performed an ileocecal resection and Kono-S anastomosis. Both patients showed no recurrence after surgery. Kono-S anastomosis may be effective for preventing recurrence at anastomotic sites in CD patients.

1031 Integration of Transcriptomics and Metabonomics: Improving Diagnostics and Phenotyping in Ulcerative Colitis

1030 Distinctive Urinary Metabolite Profiles Correlate With Microbial Composition and Are Linked With Endoscopic Post-Operative Disease Recurrence in Crohn's Disease Patients

Background During the course of inflammatory bowel disease (IBD), approximately 20% of patients with ulcerative colitis (UC) and 80% of Crohn’s disease (CD) patients will require surgery. The most common operation is total proctocolectomy and ileoanal pouch anastomosis (IPAA) for UC patients and ileocecal (IC) resection for CD. In pregnant IBD patients, guidelines name the presence of IPAA as a relative indication for Cesarean section (C-section). The effect of prior IBD-related surgery on mode of delivery and pregnancy-related outcomes remains unknown. Aims To describe pregnancy-related outcomes in pregnant women with IBD who have undergone prior IBD-related surgery. Methods We performed a retrospective cohort study of pregnant women with IBD including those with prior IBD-related surgeries including IPAA, IC resection, total or partial colectomy and ileostomy formation who delivered an infant at our medical center from 2016 to 2020. We assessed the mode of delivery, delivery characteristics (emergency vs. planned C-section) and maternal and neonatal outcomes Results Fifty-six UC patients and 64 CD patients were included in the analysis, of which 10 and 24 had undergone prior IBD-related surgery, respectively. The mean age at conception was 34.10 years in the surgical UC group and 30.30 years in the surgical CD group. Mode of delivery: C-section rates were higher in post-surgical compared to non-surgical UC patients (70% vs. 30.4%, p = 0.02). Similar numbers of C-sections were performed emergently in the surgical compared to non-surgical UC group (10% vs. 18%, p = 0.53). Comparatively, there was no significant difference in C-section rates in post -surgical compared to non-surgical CD mothers (50% vs. 40%, p = 0.44), with 13% performed emergently in both groups. Maternal outcomes: Gestational diabetes developed in 10% of surgical UC and 4.5% of surgical CD patients. Premature rupture of membranes developed in 10% of surgical UC and 9.1% of surgical CD patients. There was no difference in pre-eclampsia rates in the surgical and non-surgical CD groups (9.1% vs 13.2%, p = 0.64). Neonatal outcomes: There was no significant difference in pre-term birth rates in post-surgical compared to non-surgical UC mothers (10% vs. 15.2%, p = 0.67) or in surgical compared to non-surgical CD mothers (13.6% vs. 5.1%, p = 0.29). Neonatal Intensive Care Unit (NICU) requirements were higher in infants born to post-surgical CD compared to non-surgical CD mothers (18.2% vs. 2.7%, p = 0.04). More low birth weight (LBW) infants were born to post-surgical CD vs non-surgical CD mothers (13.6% vs. 0%, p = 0.02). Conclusions Women with IBD who have had prior IBD-related surgery may be at increased risk of developing adverse gestational and neonatal outcomes. Women with surgical UC have an increased incidence of Cesarean delivery. Funding Agencies None

Objective To compare the clinical features and endoscopic findings of Crohn's disease(CD) and intestinal tuberculosis(ITB) in order to differentiate CD from ITB. Methods The clinical and endoscopic data from 168 patients with CD and 156 patients with ITB between June 2003 and February 2009 were retrospectively analyzed. Results The salient features of CD were male patients in predominance (male : female was 108 :60) and high incidence of colectomy (CD 33.3% vs ITB 10.9%, P<0.01). Diarrhea (66.1%), hematochezia (32.1%), perianal disease (16.1%), intestinal obstruction (28.0%) were more frequent in CD patients than in ITB patients (47.0%, 7.7%, 3.4%, 9.4% respectively, all P values<0.05). The salient features of ITB were night sweating, pulmonary tuberculosis, ascites, hyperglobulin, increased erythrocyte sedimentation rate and the positive serum antibody to mycobacterium. The endoscopic examination showed that the fissure-shape ulcer, grid-shape ulcer, cobblestone sign and intestinal stricture were more frequent in CD patients than in ITB patients (all P values <0.05). Whereas the circular ulcer and involved ileocecal valve with fixed bouche shape were more common in ITB patients (P<0.05). Conclusions The clinical characteristics are different in CD and ITB patients. The endoscopic findings including fissure-shape ulcer, grid-shape ulcer, circular ulcer, cobblestone sign and the status of involved ileocecal valve are important in the differentiation of ITB from CD. Key words: Crohns disease; Intestinal tuberculosis; Clinic; Endoscopy; Diagnosis; differential

Background: There is still some discrepancy about the accuracy of faecal calprotectin (FC) in Crohn's disease (CD) patients after ileocecal resection and data from real daily practise on this topic is still scarce. Methods: For this purpose we prospectively gathered the simultaneous FC results of CD patients who were referred to the endoscopy unit in the postoperative (postop) setting. Patients with upper GI involvement were excluded. Demographic data like age, sex, disease duration, Rutgeerts score, FC, CRP results were all noted. All patients gave a stool sample 24 hours before colonoscopy and FC was determined via ELISA (Quantum Blue Calprotectin, Bühlmann Lab. AG, Switzerland). Results: Seventy-four CD patients [38 female (51%)] with an ileoceal resection were enrolled into the study protocol. Their mean age was 38.56±12 yr. with a mean disease duration of 123.52±84.88 mo. Fourty-four of 74 (60%) patients were in endoscopic remission whereas 30 (40%) had endoscopic relapse [i0- 31 patients (42%); i1- 13 patients (18%), i2- 11 patients (15%), i3- 14 patients (19%), i4- 5 patients (6%)]. Nonparametric Spearman correlation test only revealed that FC using a cut off of 30 μg/g weakly correlated with endoscopic relapse (r=0.329, p=0.004). Diagnostic accuracies of FC using different cut offs is shown in Table 1. Table 1 Diagnostic performance of FC regarding endoscopic relapse using different cut offs Conclusions: According to our results from our daily routine practise, the very low specificity of FC for each cut off in CD patients with an ileocecal resection lets us question the diagnostic utility of this non-invasive marker as an alternative tool to colonoscopy in the postop setting. A speculative explanation for this could either be the presence of unidentified lesions proximal to the ileocolonic anastomosis or ischemic anastomotic ulcers which might have been the reason behind the confusion of the endoscopist and let us judge the value of Rutgeerts score.