Postoperative Crohn's Disease Research Articles

Long-term risk of delayed postoperative Crohn's disease recurrence in patients with no or mild endoscopic recurrence at first assessment.

Early endoscopic evaluation is recommended for assessment of postoperative recurrence (POR) of Crohn's disease (CD) but no further monitoring recommendations are available. To evaluate the long-term outcome of patients without endoscopic POR at first endoscopic assessment. Retrospective four-centre study including consecutive CD patients with ileocolonic resection (ICR) without endoscopic POR (Rutgeerts score i0-i1) at first endoscopic assessment performed within 18 months from ICR. All patients had a clinical follow-up ≥24 months and at least one further endoscopic assessment. Main outcomes were endoscopic, clinical and surgical POR, need for rescue therapy and "delayed POR" (any need for rescue therapy or clinical or surgical POR) during follow-up. Overall, 183 patients were included (79% with risk factors for POR, 44% without postoperative prophylaxis). Endoscopic POR was observed in 42% of patients. Clinical POR-free survival was 89.4% and 81.5% at 3 and 5 years, and delayed POR-free survival was 76.9% and 63.4% at 5 and 10 years, respectively. In multivariate analysis, postoperative prophylaxis (HR .55; 95% CI .325-.942) and active smoking (HR 1.72; 95%CI 1.003-2.962) were independent risk factors for clinical POR, whereas presence of mild endoscopic lesions at index ileocolonoscopy (i1) was the only risk factor for delayed POR (HR 1.824; 95% CI 1.108-3.002). Long-term risk of POR among patients with no or mild endoscopic lesions at first ileocolonoscopy after surgery is steadily low, being higher among smokers, in the absence of postoperative prophylaxis and when mild endoscopic lesions are observed in the first endoscopic assessment.

Management of Post-Operative Crohn's Disease: Knowns and Unknowns.

Crohn's disease (CD) is a chronic inflammatory disorder of the gastrointestinal tract characterized by relapsing-remission phases. CD often requires surgical intervention during its course, mainly ileo-cecal/ileo-colonic resection. However, surgery in CD is not curative and post-operative recurrence (POR) can happen. The management of CD after surgery presents challenges. Ensuring timely, effective, and safe therapy to prevent POR is essential but difficult, considering that approximately 20-30% of subjects may not experience endoscopic POR and that 40-50% will only exhibit intermediate lesions, which carry a low risk of mid- and long-term clinical and surgical POR. Currently, there are two accepted intervention strategies: early post-operative prophylactic therapy (systematically or based on the patient's risk of recurrence) or starting therapy after confirming endoscopic POR 6-12 months after surgery (endoscopy-driven prophylactic therapy). The risk of overtreatment lies in exposing patients to undesired adverse events, along with the costs associated with medications. Conversely, undertreatment may lead to missed opportunities to prevent bowel damage and the necessity for additional surgery. This article aims to perform a comprehensive review regarding the optimal strategy to reduce the risk of POR in CD patients and the current therapeutic options.

Interobserver agreement of current and new proposed endoscopic scores for postoperative recurrence in Crohn’s disease

Background and AimsThe modified Rutgeerts’ score (mRS) is widely used for the assessment of endoscopic postoperative recurrence (ePOR) in Crohn’s disease (CD) after ileocolic resection to guide therapeutic decisions. To improve the validity and prognostic value of this endoscopic assessment, two new scores have been proposed. This study assessed the interobserver agreement of the current (mRS) and new endoscopic scores for ePOR in CD. MethodsSixteen Dutch academic and non-academic IBD specialists assessed endoscopic videos (n=71) of postoperative CD patients (n=66) retrieved from nine Dutch centers. Each video was assessed for the degree of inflammation by four gastroenterologists using the mRS and the new proposed endoscopic score: REMIND score (separate score of anastomosis and neoterminal ileum) and updated Rutgeerts score (assessment of lesions at the anastomotic line, ileal inlet, ileal body and neoterminal ileum). In addition, lesions at the ileal body, ileal inlet, neoterminal ileum, colonic and/or ileal blind loop were separately assessed. Interobserver agreement was assessed using Fleiss’ weighted kappa. ResultsFleiss’ weighted kappa for the mRS was 0.67 (95% confidence interval [CI] 0.59–0.74). The weighted kappa for the REMIND score was 0.73 (95% CI 0.65–0.80) for lesions in the neoterminal ileum and 0.46 (95% CI 0.35–0.58) for anastomotic lesions. The weighted kappa for the updated Rutgeerts’ score was 0.69 (95% CI 0.62–0.77). The weighted kappa for lesions in the ileal body, ileal inlet, neoterminal ileum, colonic and ileal blind loop was 0.61 (95% CI 0.49–0.73), 0.63 (95% CI 0.54–0.72), 0.61 (95% CI 0.49–0.74), 0.83 (95% CI 0.62–1.00) and 0.68 (95% CI 0.46–0.89). ConclusionThe interobserver agreement of the mRS is substantial. Similarly, the interobserver agreement is substantial for the updated Rutgeerts’ score. According to the REMIND score, the interobserver agreement was substantial for lesions in the neoterminal ileum, whereas only moderate for anastomotic lesions. Since therapeutic decisions in clinical practice are based on these assessments and these scores are used as outcome measure in clinical studies, further improvement of the interobserver agreement is essential.

P292 Endoscopic findings in ileocolic anastomoses: Crohn's disease vs oncologic surgery

Abstract Background Endoscopic lesions of ileocolic anastomoses (ICA) are frequent findings in postoperative Crohn's Disease (CD) patients, associating with the risk of future recurrence by the modified Rutgeerts score (mRS). However, erosions and ulcers, mostly idiopathic, have also been described in colorectal cancer surgery anatomoses. Methods Primary aim: to evaluate the incidence of ICA lesions in CD and their impact on therapeutic choices. Secondary aim: to compare the endoscopic findings of ICAs in CD with those of patients operated for right colon adenocarcinoma (ICA-CRC). We performed a single-center retrospective study where we included all patients with CD submitted to ileocolic anastomoses and endoscopic reassessment up to 2 years after surgery (2010 to 2023). We randomly selected ICA-CRC patients with surveillance colonoscopy within the same interval. Results 23 patients with CD; 48% male; age at date of surgery 18-65 years (median 41). Prior therapy: corticotherapy 14%; thiopurines 26%; anti-TNF 44%. Surgery: ileo-cecal resection 65%; right hemicolectomy 26%; previous anastomosis resection: 9%. Clavien Dindo ≥1: 9%. Surveillance colonoscopy: 4-24 months after surgery (mean 11); ICA assessed in 83%; Lesions in ICA-CD 60%: ulcers 46%; erosions 43%; stenosis 4%; mRS ≥2a: 30%; Therapeutic change: 60%. 66 with ICA-CRC; mean age 67years; adjuvant therapy 26%; cardiovascular risk factors 22%; Clavien Dindo ≥1: 22%; Surveillance colonoscopy (mean): 12 months after surgery; ICA lesions 4% (erosions). No patient with erosions had symptoms and no therapy was introduced. Comparing the two groups: CD patients were younger (p <0.001), had fewer postoperative complications (p 0.01) and more often had ICA lesions (p <0.001). Conclusion ICA lesions in CD, compared to ICA-CRC, were more frequent, despite the younger age of the patients and fewer postoperative complications, which favors CD recurrence. Erosions in ICA-CRC appear to have no clinical relevance.

P277 Interobserver agreement of current and new proposed endoscopic scores for postoperative recurrence in Crohn’s disease

Abstract Background The modified Rutgeerts’ score (mRS) is widely used for the assessment of endoscopic postoperative recurrence (ePOR) in Crohn’s disease (CD) after ileocolic resection to guide therapeutic decisions. To improve the validity and prognostic value of this endoscopic assessment, two new scores have been proposed. This study assessed the interobserver agreement of the current (mRS) and new endoscopic scores for ePOR in CD. Methods Sixteen academic and non-academic IBD specialists assessed endoscopic videos (n=71) of postoperative CD patients (n=66) retrieved from nine Dutch centers. Each video was assessed for the degree of inflammation by four gastroenterologists using the mRS, REMIND score (separate score of anastomosis and neoterminal ileum) and anatomic score (separate score of lesions at the anastomotic line, ileal body, ileal inlet, neoterminal ileum, colonic and/or ileal blind loop). Interobserver agreement was assessed using Fleiss’ weighted kappa. Results Fleiss’ weighted kappa for the mRS was 0.67 (95% confidence interval [CI] 0.59–0.74). The weighted kappa for the REMIND score was 0.73 (95% CI 0.65–0.80) for lesions in the neoterminal ileum and 0.46 (95% CI 0.35–0.58) for anastomotic lesions. In the anatomic score, the weighted kappa for lesions in the ileal body, ileal inlet, neoterminal ileum, colonic and ileal blind loop was 0.61 (95% CI 0.49–0.73), 0.63 (95% CI 0.54–0.72), 0.61 (95% CI 0.49–0.74), 0.83 (95% CI 0.62–1.00) and 0.68 (95% CI 0.46–0.89), and 0.44 (95% CI 0.32–0.55) for lesions at the anastomotic line. Conclusion The interobserver agreement of the mRS is substantial. Similarly, the interobserver agreement is substantial for lesions in the neoterminal ileum according to both the REMIND and anatomic score, whereas only moderate for anastomotic lesions. Since therapeutic decisions in clinical practice are based on these assessments and these scores are used as outcome measure in clinical studies, further improvement of agreement is essential.

DOP35 Spatial transcriptomics reveals cellular niches associated with histological inflammation in postoperative Crohn’s Disease

Abstract Background Postoperative Crohn’s disease (CD) recurs in ~70% of patients ≤1 year following ileocolonic resection (ICR), as observed endoscopically. Current understanding of molecular determinants underlying histological intestinal inflammation in patients with postoperative CD recurrence is minimal. To address this issue, we used advanced spatial transcriptomic analyses on intestinal biopsy samples with matched histological and endoscopic assessments from neoterminal ileum, anastomosis, and colon of patients with CD who had undergone colonoscopy following ICR. Methods Formalin-fixed paraffin-embedded (FFPE) tissue biopsies from neoterminal ileum, anastomosis, and colon were prospectively collected from a 15-patient cross-sectional cohort with CD who underwent routine endoscopic assessment following ICR. Spatial transcriptomics was performed on samples using 10X Genomics Visium CytAssist Spatial Gene Expression for FFPE V2.0. Annotation of tissue regions of histologically active inflammation and classification of histologically inactive (Robarts Histopathology Index ≤3 with subscores of 0 for neutrophils in the lamina propria and epithelium) or active disease were performed by an expert gastrointestinal pathologist. R programming language was used for data analysis (Figure). Results Fourteen of the 43 (32.6%) FFPE biopsies had histological evidence of inflammation. Spatial transcriptomics clustering revealed a distinct transcriptional signature by the segregation of 4 clusters ("inflamed clusters") composed mostly (≥69%) of cells from samples defined by histologically active disease. Tissue regions identified as inflamed by expert pathologist annotation contributed to >46% of inflamed clusters’ composition and <15% of remaining clusters. Cell type decomposition and cellular niche analysis revealed immune (e.g., myeloid, T cells, and B cells) and epithelial cells in close proximity sharing a similar microenvironment in 3 inflamed clusters while the 4th cluster was composed of >90% epithelial cells. Differentially expressed genes from the inflamed clusters were similarly expressed across intestinal segments including inflamed anastomotic biopsies and were enriched for signalling pathways involving immune cells recruitment/activation, inflammatory signalling, extracellular matrix organisation, and oxidative stress response. Conclusion This is the first study to explore spatial transcriptomic signatures associated with histological inflammation in patients with postoperative CD recurrence. Our analysis revealed a spatial signature of cellular niches and signalling pathways arising upon histological inflammation, providing insight into therapeutic targets and biomarkers across anatomic locations and the anastomosis.

P750 Endoscopic balloon dilation associated with biological therapy in Crohn's Disease strictures: a single center experience

Abstract Background Symptomatic luminal stricture in Crohn’s Disease (CD) occurs in up to 20% of patients at the diagnosis and in more than 50% during their lifetime. A considerable percentage of patients often require further surgery for post-operative CD recurrence, with a consequent increased burden of short bowel syndrome. In this scenario, combining biological therapy with endoscopic balloon dilation (EBD) could potentially reduce this risk. Our study aimed to evaluate the efficacy of EBD combined with biologic therapy in symptomatic gastrointestinal strictures in CD patients. Methods We conducted a retrospective study including consecutive CD patients who underwent EBD for low gastrointestinal strictures from December 2015 until November 2022 at our tertiary IBD Center. Subsequent subocclusive/occlusive episodes, the need for steroids, and surgery due to CD stenosis were evaluated during a follow-up period of 6 and 12 months. Results A total of 52 patients treated with EBD with an overall number of 55 strictures were included. The mean age was 46,8 (18-77) years. The median of disease duration was 9 (0-42) years. Among the total of 55 studied strictures: 14 (25%) in patients with active smoking, 21 (38%) with increased CRP values at the time of dilation, 43 (78%) had evidence of moderate or severe endoscopic disease activity with ulcerative lesions at stricture site. Anastomotic strictures accounted for 26 (47%) of all 55 strictures. The remaining 29 (53%) were de novo stricture: 8 (15%) ileal, 11 (20%) at ileocecal valve, 4 (7%) colonic, and 6 (11%) anal . Forty-two patients (76%) were under biologic therapy at the time of EBD and 2 (4%) started after EBD. EBD technical success was reported in 60% of the procedures, and no adverse events were recorded. After 6 months from EBD, at univariate analysis, increased CRP at the time of dilation resulted in a risk factor for the need for steroids (OR 14,63, IC 2,690 to 71,50; p-value = 0,0006, Table 2). Concomitant biological therapy, active smoke, and the presence of ulcerative lesions did not show a significant correlation with considered outcomes. After 12 months from EBD, concomitant biological therapy resulted in being a protective factor for surgery (OR 0,06; IC 0,005 to 0,502; p-value=0,0047), while subocclusive and occlusive events were less frequent in anastomotic strictures than ileal stenosis (OR 0,07; IC 0,005 to 0,651; p-value=0,0152). Conclusion In patients with CD undergoing EBD for intestinal CD stricture, concomitant biological therapy reduces the risk of surgery for CD stenosis recurrence. Further prospective and controlled studies are underway to confirm these observations.

Role of visceral fat on postoperative complications and relapse in patients with Crohn's disease after ileocecal resection: Is it overrated?

The role of visceral fat in disease development, particularly in Crohn´s disease (CD), is significant. However, its preoperative prognostic value for postoperative complications and CD relapse after ileocecal resection (ICR) remains unknown. This study aims to assess the predictive potential of preoperatively measured visceral and subcutaneous fat in postoperative complications and CD recurrence using magnetic resonance imaging (MRI). The primary endpoint was postoperative anastomotic leakage of the ileocolonic anastomosis, with secondary endpoints evaluating postoperative complications according to the Clavien Dindo classification and CD recurrence at the anastomosis. We conducted a retrospective analysis of 347 CD patients who underwent ICR at our tertiary referral center between 2010 and 2020. We included 223 patients with high-quality preoperative MRI scans, recording demographics, postoperative outcomes, and CD recurrence rates at the anastomosis. To assess adipose tissue distribution, we measured total fat area (TFA), visceral fat area (VFA), subcutaneous fat area (SFA), and abdominal circumference (AC) at the lumbar 3 (L3) level using MRI cross-sectional images. Ratios of these values were calculated. None of the radiological variables showed an association with anastomotic leakage (TFA p = 0.932, VFA p = 0.982, SFA p = 0.951, SFA/TFA p = 0.422, VFA/TFA p = 0.422), postoperative complications, or CD recurrence (TFA p = 0.264, VFA p = 0.916, SFA p = 0.103, SFA/TFA p = 0.059, VFA/TFA p = 0.059). Radiological visceral obesity variables were associated with postoperative outcomes or clinical recurrence in CD patients undergoing ICR. Preoperative measurement of visceral fat measurement is not specific for predicting postoperative complications or CD relapse.

Clinical Update on the Prevention and Management of Postoperative Crohn's Disease Recurrence.

Despite advances in therapeutics, a significant portion of patients with Crohn's disease still require surgical management. In this article, we present updates to the natural history, prognostication and postoperative monitoring, and novel therapeutics in the prevention and treatment of postoperative Crohn's disease recurrence. Clinical risk factors have been associated with higher rates of postoperative recurrence (POR), and in recent studies demonstrate an increased cumulative risk with presence of additional risk factors. Additional novel clinical, histologic, and "-omic" risk factors for recurrence have recently been elucidated, including the role of the mesentery on recurrence and perioperative intraabdominal septic complications. High-risk patients benefit most from medical prophylaxis, including anti-TNF with or without immunomodulator therapy to prevent recurrence. New biologics such as vedolizumab and ustekinumab have emerging evidence in the use of prophylaxis, especially with recent REPREVIO trial data. Non-invasive disease monitoring, such as cross-sectional enterography, intestinal ultrasound, and fecal calprotectin, have been validated against ileocolonoscopy. Recent advances in the prediction, prevention, and monitoring algorithms of postoperative Crohn's disease may be leading to a reduction in postoperative recurrence. Ongoing trials will help determine optimal monitoring and management strategies for this at-risk population.

Early Initiation of Adalimumab Significantly Diminishes Postoperative Crohn's Disease Endoscopic Recurrence and Is Superior to 6-Mercaptopurine Therapy: An Open-Label, Randomized Controlled Study.

Postoperative recurrence (POR) is the rule in patients with Crohn's disease (CD), mitigated with prophylactic therapy. The evidence for therapeutic choice and timing of intervention is lacking. We aimed to compare the rates of POR in patients treated early with prophylactic 6-mercaptopurine (6-MP) or adalimumab. We conducted a prospective single-center randomized open-label clinical study in which patients in surgical remission following their first ileocecectomy were randomized to receive early treatment with 6-MP or adalimumab. Patients were followed up clinically every 3 months and underwent endoscopy at weeks 32 and 58 postoperatively. The primary endpoint was endoscopic recurrence (ePOR) at 1 year (week 58), defined as a Rutgeerts score ≥ i2. We enrolled 35 patients (25 males, mean age 35 ± 1.4 years, median disease duration 5 ± 6.1 years) following ileocecectomy. Of these, seven (20%) were current smokers and nine (26%) biologics-experienced. Patients allocated to adalimumab had significantly less ePOR than patients treated with 6MP at week 32 (21% vs. 69%, p = 0.004) and 58 (47% vs. 75%), (p = 0.03, HR = 0.39, 95% CI = 0.16-0.93). POR was associated with an increased diameter of the resected small bowel surgical specimen, lower baseline body mass index (BMI), increased week 18 fecal calprotectin, increased week 18 serum alanine aminotransferase and decreased week 18 hemoglobin level. Adalimumab was more effective than 6-MP in preventing ePOR. Increased operative small bowel diameter and lower postoperative BMI were associated with ePOR. At eighteen weeks, serum hemoglobin, ALT and fecal calprotectin levels were predictive of endoscopic disease recurrence. (ClinicalTrials.gov ID NCT01629628).

Real-World Surgical and Endoscopic Recurrence Based on Risk Profiles and Prophylaxis Utilization in Postoperative Crohn’s Disease

Background & AimsPreoperative risk stratification may help guide prophylactic biologic utilization for the prevention of postoperative Crohn's disease (CD) recurrence; however, there is limited data exploring and validating proposed clinical risk factors. We aimed to explore preoperative clinical risk profiles, quantify individual risk factors, and assess the impact of biologic prophylaxis on postoperative recurrence (POR) risk in a real-world cohort. MethodsIn this multicenter retrospective analysis, patients with CD who underwent ileocecal resection (ICR) from 2009-2020 were identified. High-risk (active smoking, ≥2 prior surgeries, penetrating and/or perianal disease) and low-risk (nonsmokers and age>50 years) features were used to stratify patients. We assessed the risk of endoscopic (Rutgeerts’ score ≥i2b) and surgical recurrence by risk strata and biologic prophylaxis (≤90 days postoperatively) with logistic and time-to-event analyses. ResultsA total of 1404 adult CD patients who underwent ICR were included. Of the high-risk factors, ≥2 ICR (OR 1.71; 95% CI [1.13-2.57]), active smoking (OR 1.73, 95% CI [1.17-2.53]), penetrating disease (OR 1.41, 95% CI [1.02-1.94]), and history of perianal disease alone (OR 1.99, 95% CI [1.42-2.79]) were associated with surgical but not endoscopic recurrence. Surgical recurrence was lower in high-risk patients receiving prophylaxis versus not (10.2% vs 16.7%; p=0.02), and endoscopic recurrence was lower in those receiving prophylaxis irrespective of risk strata (High-risk: 28.1% vs 37.4%; p=0.03 and Low-risk: 21.1% vs 38.3%; p=0.002). ConclusionsClinical risk factors accurately illustrate patients at risk for surgical recurrence, but have limited utility in predicting endoscopic recurrence. Biologic prophylaxis may be of benefit irrespective of risk stratification and future studies should assess this.

Capsule Endoscopy in Inflammatory Bowel Disease: A Systematic Review

AbstractThe role of video capsule endoscopy (VCE) in inflammatory bowel disease (IBD) has evolved from small bowel to a panenteric evaluation tool over the past two decades. We systematically reviewed the techniques, applications, outcomes, and complications of VCE in IBD. A systematic literature search was performed using PubMed, Embase, and Medline. All relevant original articles involving VCE in IBD were included from 2003 to July 2022. After screening 3,089 citations, finally 201 references were included. The diagnostic yield of VCE in suspected Crohn's disease (CD) was highly variable (6–80%) with excellent sensitivity (77–93%) and specificity (80–89%). The diagnostic yield in known CD was 52 to 88.3% leading to a change in management (26–75%) and disease reclassification with variable retention rates. VCE was superior to small bowel series, computed tomography (CT) and could be better than magnetic resonance enterography (MRE), especially for proximal and superficial lesions. Colon or panenteric VCE has strong correlation to ileo-colonoscopy (IC) and combined magnetic resonance imaging and IC, respectively. The VCE retention rate in CD is higher in known CD which significantly decreases after the negative patency capsule test or CT/MRE. VCE can identify lesions beyond the reach of IC in postoperative CD. Colon Capsule Endoscopy is a noninvasive monitoring tool in ulcerative colitis (UC) having a strong correlation with IC and may uncover small bowel involvement. VCE is specifically useful in IBD-unclassified (IBD-U) which can lead to the diagnosis of CD in 16.7 to 61.5%. Various scoring systems have been established and validated for small bowel CD (Lewis score and capsule endoscopy CD activity index—CECDAI), UC (capsule scoring of UC: Capsule Scoring of Ulcerative Colitis), panenteric evaluation (Capsule Endoscopy Crohn's Disease Activity Index, Elaikim score), and flare prediction (APEX score). Technological advances include double head, three-dimensional reconstruction, sampling system, panoramic view (344 and 360 degree lateral), and panenteric capsule. Artificial intelligence and software like TOP100 and Quickview can help reduce capsule reading time with excellent sensitivity and specificity. VCE in IBD has widespread application in suspected and known small bowel CD, monitoring of UC, postoperative CD, IBD-U, and for panenteric evaluation. Patency capsule testing helps to reduce retention rates significantly. Artificial intelligence and technical advances can help evolve this novel technology.

Postoperative Crohn's Disease.

Although surgery rates in Crohn's disease are declining in the past twenty years, bowel resection remains an important and still commonly used therapeutic option in Crohn's disease. Preoperatively, patients clinical status must be optimized including preparation for perioperative recovery including with nutrition optimization and preparation for postoperative pharmacotherapy. Postoperatively a medical therapy is often required and in recent years it has often been a biological therapy. One randomized controlled study suggested that infliximab is more likely to prevent endoscopic recurrence than placebo. But other biologicals have been used as well. Ileocolonoscopy should be undertaken by 6 months after an ileal or ileocecal resection especially. Adjunctive imaging such as transabdominal ultrasound, capsule endoscopy or cross sectional imaging may be required. Biomarker measurement with fecal calprotectin especially, or C-reactive protein, serum ferritin, serum albumin and serum hemoglobin will also be helpful.

Suboptimal Guideline Adherence and Biomarker Underutilization in Monitoring of Post-operative Crohn's Disease.

Crohn's disease recurrence after ileocecal resection is common. Guidelines suggest colonoscopy within 6-12months of surgery to assess for post-operative recurrence, but use of adjunctive monitoring is not protocolized. We aimed to describe the state of monitoring in post-operative Crohn's. We conducted a retrospective study of patients with Crohn's after ileocolic resection with ≥ 1-year follow-up. Patients were stratified into high and low risk based on guidelines. Post-operative biomarker (C-reactive protein, fecal calprotectin), cross-sectional imaging, and colonoscopy use were assessed. Biomarker, radiographic, and endoscopic post-operative recurrence were defined as elevated CRP/calprotectin, active inflammation on imaging, and Rutgeerts ≥ i2b, respectively. Data were stratified by surgery year to assess changes in practice patterns over time. P-values were calculated using Wilcoxon test and Fisher exact test. Of 901 patients, 53% were female and 78% high risk. Median follow-up time was 60m for LR and 50m for high risk. Postoperatively, 18% low and 38% high risk had CRPs, 5% low and 10% high risk had calprotectins, and half of low and high risk had cross-sectional imaging. 29% low and 38% high risk had colonoscopy by 1year. Compared to pre-2015, time to first radiography (584days vs. 398days) and colonoscopy (421days vs. 296days) were significantly shorter for high-risk post-2015 (P < 0.001). Probability of colonoscopy within 1year increased over time (0.48, 2011 vs. 0.92, 2019). Post-operative colonoscopy completion by 1year is low. The use of CRP and imaging are common, whereas calprotectin is infrequently utilized. Practice patterns are shifting toward earlier monitoring.

Anastomotic Configuration and Temporary Diverting Ileostomy Do Not Increase Risk of Anastomotic Stricture in Postoperative Crohn's Disease.

Surgical management of Crohn's disease (CD) is common. Postoperative complications include anastomotic stricturing (AS). The natural history and risk factors for AS have not been elucidated. A retrospective cohort study of patients with CD who underwent ileocolonic resection (ICR) with ≥1 postoperative ileocolonoscopy between 2009 and 2020. Postoperative ileocolonoscopies with corresponding cross-sectional imaging were evaluated for evidence of AS without neoterminal ileal extension. Severity of AS and endoscopic intervention at time of detection were collected. Primary outcome was development of AS. Secondary outcome was time to AS detection. A total of 602 adult patients with CD underwent ICR with postoperative ileocolonoscopy. Of these, 426 had primary anastomosis, and 136 had temporary diversion at time of ICR. Anastomotic configuration consisted of 308 side-to-side, 148 end-to-side, and 136 end-to-end. One hundred ten (18.3%) patients developed AS with median time of 3.2 years to AS detection. AS severity at time of detection was associated with need for repeat surgical resection for AS. On multivariable Cox proportional hazard regression, anastomotic configuration and temporary diversion were not associated with risk of or time to AS. Preoperative stricturing disease was associated with decreased time to AS (adjusted hazard ratio 1.8; P = 0.049). Endoscopic ileal recurrence before AS was not associated with subsequent AS detection. AS is a relatively common postoperative CD complication. Patients with previous stricturing disease behavior are at increased risk of AS. Anastomotic configuration, temporary diversion, and ileal CD recurrence do not increase risk of AS. Early detection and intervention for AS may help prevent progression to repeat ICR.

Effect of food additives on key bacterial taxa and the mucosa-associated microbiota in Crohn’s disease. The ENIGMA study

ABSTRACT Food additives have been linked to the pro-inflammatory microbial dysbiosis associated with Crohn’s disease (CD) but the underlying ecological dynamics are unknown. Here, we examine how selection of food additives affects the growth of multiple strains of a key beneficial bacterium (Faecalibacterium prausnitzii), axenic clinical isolates of proinflammatory bacteria from CD patients (Proteus, Morganella, and Klebsiella spp.), and the consortia of mucosa-associated microbiota recovered from multiple Crohn’s disease patients. Bacterial growth of the axenic isolates was evaluated using a habitat-simulating medium supplemented with either sodium sulfite, aluminum silicate, carrageenan, carboxymethylcellulose, polysorbate 80, saccharin, sucralose, or aspartame, intended to approximate concentrations found in food. The microbial consortia recovered from post-operative CD patient mucosal biopsy samples were challenged with either carboxymethylcellulose and/or polysorbate 80, and the bacterial communities compared to unchallenged consortia by 16S rRNA gene amplicon profiling. Growth of all F. prausnitzii strains was arrested when either sodium sulfite or polysorbate 80 was added to cultures at baseline or mid-exponential phase of growth, and the inhibitory effects on the Gram-negative bacteria by sodium sulfite were conditional on oxygen availability. The effects from polysorbate 80, saccharin, carrageenan, and/or carboxymethylcellulose on these bacteria were strain-specific. In addition to their direct effects on bacterial growth, polysorbate 80 and/or carboxymethylcellulose can drive profound changes in the CD mucosa-associated microbiota via niche expansion of Proteus and/or Veillonellaceae – both implicated in early Crohn’s disease recurrence. These studies on the interaction of food additives with the enteric microbiota provide a basis for dietary management in Crohn’s disease.

Granuloma Presence at Initial Surgery Predicts Need for Repeat Surgery Independent of Rutgeerts Score in Crohn's Disease.

Approximately half of Crohn's disease (CD) patients experience recurrence and need for repeat resections, highlighting need for prognostic biomarkers. Presence of epithelioid granuloma on surgical tissue and high Rutgeerts endoscopic score are associated with postoperative CD clinical recurrence. We sought to evaluate presence of epithelioid granuloma at first surgery and Rutgeerts score as a combined risk assessment for CD surgical recurrence. Our study included consented CD patients who underwent initial ileocecal resection and were prospectively followed postoperatively. From 2009 to 2019, 418 CD patients underwent initial ileocecal resection with >4 years of follow-up, including postoperative endoscopic assessment (Rutgeerts score). Postoperative CD patients were grouped based on granuloma presence (30.6%; n = 128) or absence (69.4%; n = 290). Endoscopic recurrence (defined as Rutgeerts score ≥i2) was similar between the granuloma (26%) and no granuloma (25%) groups, respectively (P = .82). Patients with granuloma and CD endoscopic recurrence at first postoperative endoscopy had higher number of bowel surgeries compared with all other groups (no granuloma or CD endoscopic recurrence, P = .007; no granuloma but CD endoscopic recurrence present, P = .04; granuloma present and no CD endoscopic recurrence, P = .04). Epithelioid granuloma presence was associated with 1.65 times higher risk of subsequent surgery independently from first postoperative endoscopic recurrence Rutgeerts score. Granuloma presence on initial surgical histology is immediately available and identifies high-risk CD patients who may benefit from early postoperative treatment, and these precision intervention trials are warranted.

P275 Anastomotic technique drives endoscopic recurrence in Postoperative Crohn's Disease: a systematic review and meta-analysis

Abstract Background Patients with Crohn's disease (CD) after Ileo-colic resection may develop an endoscopic postoperative recurrence (ePOR) that reaches approximately 70% of incidence within six months. ECCO guidelines favour a stapled side-to-side anastomosis. However, the advent of the Kono-S ileocolic anastomosis, a hand-sewn antimesenteric functional end-to-end anastomosis, seems to reduce clinical risk and ePOR. Whilst the majority of the studies have assessed the rate of ePOR individually, currently there is limited data comparing surgical techniques of the anastomosis. Hence, we aimed to assess the impact of different surgical techniques on ePOR in CD Methods We searched PubMed and Embase in October 2022 for eligible studies reporting the surgical types of anastomosis and, based on these, the rate of endoscopic recurrence at a minimum of six months. Studies were grouped by conventional anastomosis vs Kono, and comparisons were made between these groups. Pooled incidence rates of ePOR were computed using random-effect modelling. Meta-regression and subgroup analyses were performed to examine the impact of the type of anastomosis on the incidence of ePOR ≥ 6 months Results Thirteen studies, including 1816 patients who underwent ileocolic resection for CD, were included. Among these patients, 282 (15.5%) received a Kono-S anastomosis, while 1534 (84.4%) had a conventional anastomosis. ePOR at ≥≥ six months showed a pooled incidence of 31.8% (95% CI, 24.8 to 39.2), with significant heterogeneity among the studies (p&amp;lt;0.01). Meta-regression analysis showed that Kono-S anastomosis was associated with a significant reduction in the ePOR at endoscopic follow-up (p=0.001). In detail, patients receiving a Kono-S anastomosis had a pooled incidence of ePOR of 12% (95% CI, 3.1 to 24.9), while patients receiving a conventional anastomosis had an ePOR of 38.2 (95% CI, 30 to 46.9%) [Figure1]. Funnel plot asymmetry [Figure 2] and Egger's regression test (p=0.118) indicated the absence of a publication bias Conclusion Kono-S anastomosis was associated with a significant reduction of ePOR at ≥ six months compared to the conventional anastomosis. Our findings highlight the need to standardize and implement the use of Kono-S anastomosis, particularly for difficult-to-treat patients with high risk for a post-operative recurrence

OP01 Sequencing-based gene network analysis reveals a profound role for ferroptosis key gene GPX4 in post-operative endoscopic recurrence in Crohn’s disease

Abstract Background An ileocolonic resection with ileocolonic anastomosis is often required in patients with Crohn’s disease (CD). Postoperative recurrence (POR) is common, with host-luminal interactions being implicated. However, these interactions are poorly understood. We aimed to obtain insights in the early mechanisms of POR CD focusing on sequencing-based gene networks in the mucosa. Methods We included 36 CD patients who underwent ileocolonic resection with ileocolonic anastomosis, and collected mucosal biopsies from the neoterminal ileum 6 months after surgery (Table 1). We defined POR by a Rutgeerts score ≥i2b at month 6, and compared this to complete absence of endoscopic activity (i0). All biopsies underwent single-end RNA sequencing (Illumina TruSeq Stranded mRNA). Gene co-expression network clusters were identified using weighted gene co-expression network analysis (R\WGCNA), were tested for correlation with the primary outcome POR and clinical factors, and multiple testing correction was applied (FDR&amp;lt;0.05). Cellular deconvolution was performed using xCell; and top enriched pathways and upstream regulators were analysed using IPA (p&amp;lt;0.05). Results WGCNA analysis identified 25 co-expression clusters, of which five correlated with the postoperative outcome (clusters V, VI, IX, XV, XXV) (Fig.1). All but cluster XXV were upregulated in POR, with a profound immune-related enrichment in cluster V and VI (eg. (a)granulocyte adhesion and diapedesis, and IL17 signalling); microRNA biogenesis (cluster IX) and wound healing and fibrosis signalling (cluster XV). Interestingly, one cluster (XXV) was inversely correlated with POR, and genes within this cluster were mainly involved in autophagy, ferroptosis and oxidative stress response. The main hub gene (r=0.95, FDR=8.17E-19) within this cluster XXV was GPX4 (Glutathione peroxidase 4), a negative regulator of ferroptosis. Moreover, after cellular deconvolution, we found a positive correlation between the epithelial gene enrichment signature and the expression of GPX4 (r=0.52, p=0.0011). Finally, the main upstream regulator of the genes within this cluster XXV was HNF4A, a transcription factor known to regulate ferroptotic response. Conclusion We identified a mucosal transcriptomic signature associated with postoperative CD recurrence. Both autophagy and ferroptosis were found to be key protective pathways for recurrence with GPX4 as central hub. Our results complement recent findings of impaired epithelial GPX4 activity in ileal CD lesions evoking an inflammatory response to dietary lipids (Mayr et al Nat Comm 2020).

Neutrophil-to-lymphocyte ratio for predicting postoperative recurrence in Crohn's disease patients with isolated anastomotic lesions.

Patients with isolated anastomotic lesions (iAL) are common in postoperative Crohn's disease (CD) and have heterogeneous prognosis. To investigate the prognostic value of neutrophil-to-lymphocyte ratio (NLR) in CD patients with iAL. A bicenter retrospective cohort study. CD patients who received ileocolonic resection from 2013 and 2020 and had a modified Rutgeerts score of i2a were recruited. NLR was determined within 1 week around the initial endoscopy after ileocolectomy. The primary outcome was clinical recurrence. Kaplan-Meier method and Cox hazard regression analysis were utilized to assess the association between candidate variables and outcomes of interest. In total, 411 postoperative CD patients were preliminarily reviewed and 83 patients were eligible. In total, 36 (48.6%) patients experienced clinical recurrence with a median follow-up time of 16.3 (interquartile range, 9.7-26.3) months. NLR > 2.45 and age at surgery >45 years had higher cumulative incidence of clinical recurrence in the Kaplan-Meier analysis. After adjusted for potential confounders, NLR > 2.45 was the only independent risk factor for clinical recurrence, with an adjusted hazard ratio (HR) of 2.88 [95% confidence interval (CI), 1.39-6.00; p = 0.005]. Furthermore, a risk score based on NLR and age at surgery were built to further stratify patients. Compared to those who scored 0, patients with a score of 1 and 2 had an adjusted HR of 2.48 (95% CI, 1.22-5.02) and 6.97 (95% CI, 2.19-22.16) for developing clinical recurrence, respectively. NLR is a promising prognostic biomarker for CD patients with iAL. The utilization of NLR and the risk score to stratify patients may facilitate the personalized management in patients with iAL.