Postoperative Endoscopic Recurrence Research Articles

Positive resection margins in Crohn’s disease are a relevant risk factor for postoperative disease recurrence

Postoperative disease recurrence in Crohn’s disease represents a relevant issue despite recent advancements in surgical and medical therapies. Additional criteria are necessary to improve the identification of patients at risk and to enable selective therapeutic approaches. The role of resection margins on disease recurrence remains unclear and general recommendations are lacking. A single-center retrospective analysis was performed including all patients who received ileocecal resection due to Crohn’s disease. Resection margins were analyzed by two independent pathologists and defined by histopathological criteria based on previous consensus reports. 158 patients were included for analysis with a median follow up of 35 months. While postoperative morbidity was not affected, positive resection margins resulted in significantly increased rates of severe endoscopic recurrence at 6 months (2.0% versus 15.6%, p = 0.02) and overall (4.2% versus 19.6%, p = 0.001), which resulted in significantly increased numbers of surgical recurrence (0% versus 4.5%, p = 0.04). Additionally, positive margins were identified as independent risk factor for severe endoscopic disease recurrence in a multivariate analysis. Based on that, positive margins represent an independent risk factor for postoperative endoscopic and surgical disease recurrence. Prospective studies are required to determine whether extended resection or postoperative medical prophylaxis is beneficial for patients with positive resection margins.

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.

Pre-operative visceral adipose tissue radiodensity is a potentially novel prognostic biomarker for early endoscopic post-operative recurrence in Crohn's disease.

Evidence suggests inflammatory mesenteric fat is involved in post-operative recurrence (POR) of Crohn's disease (CD). However, its prognostic value is uncertain, in part, due to difficulties studying it non-invasively. To evaluate the prognostic value of pre-operative radiographic mesenteric parameters for early endoscopic POR (ePOR). We conducted a retrospective cohort study of CD subjects ≥ 12 years who underwent ileocecal or small bowel resection between 1/1/2007 to 12/31/2021 with computerized tomography abdomen/pelvis ≤ 6 months pre-operatively and underwent ileocolonoscopy ≤ 15 months post-operatively. Visceral adipose tissue (VAT) volume (cm3), ratio of VAT:subcutaneous adipose tissue (SAT) volume, VAT radiodensity, and ratio of VAT:SAT radiodensity were generated semiautomatically. Mesenteric lymphadenopathy (LAD, largest lymph node > 10 mm) and severe vasa recta (VR) engorgement (diameter of the VR supplying diseased bowel ≥ 2 × VR supplying healthy bowel) were derived manually. The primary outcome was early ePOR (Rutgeert's score ≥ i2 on first endoscopy ≤ 15 months post-operatively) and the secondary outcome was ePOR severity (Rutgeert's score i0-4). Regression analyses were performed adjusting for demographic and disease-related characteristics to calculate adjusted odds ratio (aOR) and 95% confidence interval (CI). Of the 139 subjects included, 45% of subjects developed early ePOR (n = 63). VAT radiodensity (aOR 0.59, 95%CI: 0.38-0.90) and VAT:SAT radiodensity (aOR 8.54, 95%CI: 1.48-49.28) were associated with early ePOR, whereas, VAT volume (aOR 1.23, 95%CI: 0.78-1.95), VAT:SAT volume (aOR 0.80, 95%CI: 0.53-1.20), severe VR engorgement (aOR 1.53, 95%CI: 0.64-3.66), and mesenteric LAD (aOR 1.59, 95%CI: 0.67-3.79) were not. Similar results were observed for severity of ePOR. VAT radiodensity is potentially a novel non-invasive prognostic imaging marker to help risk stratify CD patients for POR.

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.

Optimising surgical anastomosis in ileocolic resection for Crohn’s disease with respect to recurrence and functionality: two international parallel randomized controlled trials comparing handsewn (END-to-end or Kono-S) to stapled anastomosis (HAND2END and the End2End STUDIES)

BackgroundThe most common intestinal operation in Crohn’s disease (CD) is an ileocolic resection. Despite optimal surgical and medical management, recurrent disease after surgery is common. Different types of anastomoses with respect to configuration and construction can be made after resection for example, handsewn (end-to-end and Kono-S) and stapled (side-to-side). The various types of anastomoses might affect endoscopic recurrence and its assessment, the functional outcome, and costs. The objective of the present study is to compare the three types of anastomoses with respect to endoscopic recurrence at 6 months, gastrointestinal function, and health care consumption.MethodsThis is a randomized controlled multicentre superiority trial, allocating patients either to side-to-side stapled anastomosis as advised in current guidelines or a handsewn anastomoses (an end-to-end or Kono-S). It is hypothesized that handsewn anastomoses do better than stapled, and end-to-end perform better than the saccular Kono-S. Two international studies with a similar setup will be conducted mainly in the Netherlands (End2End) and Italy (HAND2END). Patients diagnosed with CD, aged over 16 years in the Netherlands and 18 years in Italy requiring (re)resection of the (neo)terminal ileum are eligible. The first part of the study compares the two handsewn anastomoses with the stapled anastomosis. To detect a clinically relevant difference of 25% in endoscopic recurrence, a total of 165 patients will be needed in the Netherlands and 189 patients in Italy. Primary outcome is postoperative endoscopic recurrence (defined as Rutgeerts score ≥ i2b) at 6 months. Secondary outcomes are postoperative morbidity, gastrointestinal function, quality of life (QoL) and costs.DiscussionThe research question addresses a knowledge gap within the general practice elucidating which type of anastomosis is superior in terms of endoscopic and clinical recurrence, functionality, QoL and health care consumption. The results of the proposed study might change current practice in contrast to what is advised by the guidelines.Trial registrationNCT05246917 for HAND2END and NCT05578235 for End2End (http://www.clinicaltrials.gov/).

P832 Postoperative fever and CRP levels as predictive markers of postoperative recurrence of Crohn’s disease after ileocolic resection

Abstract Background Studies have shown that postoperative C-reactive protein (CRP) levels in patients with Crohn’s disease (CD) undergoing ileocolic resections (ICR) are higher than in control patients operated for cancer. This study aims to verify the association between postoperative fever and CRP levels with CD recurrence. Methods We performed a single-centre retrospective study of all CD patients undergoing an ICR between 2009 and 2019. CRP levels and fever (body temperature >38.5 °C) were measured preoperatively and during the first 7 postoperative days (POD). A colonoscopy was performed within 12 months after surgery. Endoscopic postoperative recurrence (POR) was defined as a modified Rutgeerts score ≥i2b. Surgical recurrence as the need for reoperation due to CD recurrence at the level of the ileocolic anastomosis. A multivariate regression model for longitudinal measures was used to obtain estimates of postoperative CRP levels. Association between fever and estimates of CRP levels with endoscopic and surgical POR was evaluated through a multivariate analysis including sex, age, Montreal classification, use of advanced therapies prior to surgery, associated surgical procedures, smoking habit, and continuation/initiation of medical therapy after surgery. Results We identified 372 patients, of which 299 (80.4%) had complicated CD (Montreal B2+B3) and 166 (44.7%) already received advanced therapies before surgery. 92 (24.7%) were active smokers at the time of surgery. In 26 patients (7.0%), one or more strictureplasties were performed simultaneously to the ICR. Prophylactic medical treatment was restarted/initiated immediately after surgery in only 9.7% of the patients. Estimates of CRP level at POD -1, +1, +3, and +5 were 9.23 mg/L (CI 7.85;10.86), 63.05 mg/L (CI 58.63;67.80), 82.55 mg/L (CI 75.09;90.76), and 56.79 mg/L (CI 49.76;64.81), respectively. Overall, 154/367 patients (42.0%) with available body temperature measures, experienced fever postoperatively. Endoscopic POR occurred in 144/332 patients (43.37%) with an available colonoscopy within 12 months postoperatively (Table 1). Surgical POR was 7.0% (CI 4.9%-11.1%) and 11.8% (CI 5.7%-8.8%) at 3 and 5 years follow-up, respectively (Figure 1). No association between postoperative fever and CRP levels estimates with either endoscopic (p=0.49; p=0.06) or surgical POR (p=0.52; p=0.07] was observed. Conclusion Despite previous evidence suggesting that CD patients develop an enhanced postoperative inflammatory response, CRP levels and fever after ICR do not seem predictive of early endoscopic (<12 months) or long-term surgical POR. Therefore, they should not be considered to stratify patients for postoperative medical prophylactic therapy.

P818 Imaging-based preoperative body composition is associated with the risk of postoperative complications and postoperative endoscopic recurrence in patients with Crohn’s disease

Abstract Background Alterations in body composition are common in Crohn’s disease (CD) patients and influence disease outcomes. However, the impact of preoperative body composition on postoperative outcomes is not completely understood. Therefore, this study aimed to investigate the association of preoperative body composition with postoperative complications and endoscopic recurrence in CD patients undergoing ileocolic (re-)resection (ICR). Methods CD patients (≥16 years) scheduled for an ICR with a computed tomography (CT) scan available (<12 months prior to ICR) were identified from an ongoing prospective, multicenter cohort study. Skeletal muscle mass (SM), visceral (VAT) and subcutaneous adipose tissue (SAT), and their radiation attenuation (RA) were assessed on a single CT image at L3 using a validated deep-learning automatic segmentation tool (Mosamatic). Low RA is associated with increased tissue triglyceride content (e.g. myosteatosis in case of SM). Cut-offs, based on sex-specific tertiles, were set at the lower and upper tertile for low and high values. The primary outcome was the development of overall postoperative complications within 90 days. Secondary outcomes were postoperative endoscopic recurrence (Rutgeerts’ score ≥ i2b) at 6 months, infectious complications, and moderate to severe complications (Clavien-Dindo ≥ II). Multivariable logistic regression was performed to assess the association of body composition variables with postoperative outcomes, including adjustment for confounders. Results 121 patients were included (median age 37.1 years (IQR 27.1–53.2), 59.5% female). Median disease duration at surgery was 3.6 years (IQR 0.4–12.7), and 57.0% had prior exposure to ≥ 1 biological. Overall postoperative complications were reported in 51.2%, endoscopic recurrence in 33.3%, infectious complications in 26.4%, and moderate to severe complications in 41.3%. High SM-RA (aOR 0.67; 95%CI 0.16–0.85) and low VAT (aOR 0.38; 95%CI 0.17–0.87) were associated with decreased overall postoperative complications. Low VAT-RA was associated with decreased endoscopic recurrence (aOR 0.21; 95%CI 0.07–0.67), and high SAT with increased infectious complications (aOR 3.05; 95%CI 1.28–7.28). Conclusion Low visceral adipose tissue and high radiation attenuation of skeletal muscle (i.e. no myosteatosis) were protective of overall postoperative complications in CD patients undergoing ICR. Low radiation attenuation of visceral adipose tissue (i.e. high triglyceride content) was protective of endoscopic recurrence. High subcutaneous adipose tissue increased the risk of postoperative infectious complications. Further research in larger populations is warranted to validate these findings to improve preoperative stratification and strategies for CD.

P622 Network meta-analysis comparing efficacy between biologics and conventional therapies to prevent endoscopic postoperative recurrence in patients with Crohn's disease

Abstract Background As no direct comparison between IBD drugs to prevent endoscopic postoperative recurrence (POR) In Crohn’s disease (CD) are available, hierarchizing these therapeutic options remains challenging. The objective of this network meta-analysis was to compare the effectiveness of treatments to prevent endoscopic POR of CD. Methods We performed a systematic review and network meta-analysis of comparative studies conducted in adults, evaluating a treatment to prevent endoscopic POR after ileocecal resection. The selection of studies was made according to PRISMA guidelines. The primary endpoint was endoscopic POR at 6 months defined as Rutgeerts score ≥ i2. The network meta-analysis was carried out according to a random effects model. The results are presented as odds ratio (OR) with 95% confidence interval, adjusted for risk factors of POR. The risk of bias of the studies was assessed according to the Cochrane risk-of-bias tool for randomized trials and overall statistical heterogeneity between studies was assessed using τ². The SUCRA ranking method (surface under the cumulative ranking) was used to rank the treatments. Results Twenty studies were included in this network meta-analysis, including a total of 2414 patients. Overall heterogeneity was moderate (τ²=0.34). After adjustment for POR risk factors, ustekinumab (OR = 0.23 [0.07-0.70]), vedolizumab (OR = 0.17 [0.05 -0.59]), infliximab (OR = (0.18 [0.36-0.88]) and adalimumab (OR = 0.17 [0.07-0.42]) were superior to placebo to prevent endoscopic POR, contrary to 5-ASA (OR = 0.79 [0.42 -1.48]) and thiopurines (RR = 0.52 [0.22-1.24]) (Table 1). Ustekinumab (OR = 0.29 [0.08-0.99]), vedolizumab (OR = 0.22 [0.06-0.85]), infliximab (OR = (0.23 [0.09-0.54]) and adalimumab (OR = 0.22 [0.08-0.59]) were more effective than 5-ASA in preventing endoscopic POR. Adalimumab (OR = 0.33 [0.15-0.74]) and infliximab (OR = 0.34 [0.13-0.87]) were also more effective than thiopurines. We observed no difference in efficacy between the 4 biologics (infliximab, adalimumab, ustekinumab and vedolizumab) (Table 1). The SUCRA ranking identified adalimumab (SUCRA=0.81), infliximab (SUCRA=0.80), vedolizumab (SUCRA=0.79) and ustekinumab (SUCRA=0.72) as the most effective treatments. The likelihood that thiopurines (SUCRA=0.41), 5-ASA (SUCRA=0.24), placebo (SUCRA = 0.16) and antibiotics (SUCRA=0.08) was the best option is very low. Conclusion This network meta-analysis confirms the efficacy of anti-TNF agents, vedolizumab and ustekinumab in preventing endoscopic CD POR without any difference between them. When prophylactic therapy is necessary, biologics appear as the best therapeutic option to prevent of endoscopic POR. Due to lower efficacy, the use of 5-ASA and thiopurines should be limited in this situation.

P485 Do intestinal ultrasound scores have a role in the diagnosis of post-operative recurrence?

Abstract Background Ileocolonoscopy and Rutgeerts endoscopic score remains the gold standard to evaluate post-operative recurrence (POR) in Crohn's disease (CD) patients. Intestinal ultrasound (IUS) is proposed as a non-invasive alternative to ileocolonoscopy for the diagnosis of POR, with a sensitivity of 94% and specificity of 84%. There are several IUS scores that evaluate CD disease activity such as SUS-CD (validated), IBUS-SAS and Simple US Score, which have not yet been studied in the diagnosis of POR. The aim of this study is to assess whether IUS parameters and ultrasound scores correlate with endoscopy in the diagnosis of POR. Methods A unicentric retrospective study was performed. There were included patients with CD with both an ileocolonoscopy and intestinal ultrasound performed for the detection of POR, the time between tests was less than 6 months and there was no therapeutic change between tests. Endoscopic POR was evaluated with Rutgeers score (RS), considering POR RS ≥i2b. In IUS, were used: Simple US Score, SUS-CD and IBUS-SAS. Results 103 patients were included, baseline characteristics are in Table 1. 30 patients (29.1%) had no endoscopic POR, 22 (21.4%) had RS i2a, 12 (11.6%) RS i2b and 39 (37.9%) had severe POR (RS i3-i4). The mean wall thickness measured by IUS in patients without endoscopic POR was 2.7 mm (SD +/- 1.3) versus 5.0 (SD +/- 1.7) in patients with RS ≥i2b (p 0.001). Hyperemia (Limberg >1) was present in 60 patients (82.2%) with RS ≥i2a vs in 4 patients (13.3%) without endoscopic POR (p 0.001). Both hyperemia and wall thickness had a sensitivity of 89.0% and specificity of 76.7% in the diagnosis of POR. The mean values for IUS scores were: Simple US Score 5.5 (SD +/- 3.1), SUS-CD 2.1 (SD +/- 1.8) and IBUS-SAS 32.9 (SD +/- 26.3). There were positive correlation for IUS scores (Simple US Score r 0.68, SUS-CD r 0.68 and IBUS-SAS r 0.67) with RS (p <0.0001). For the Simple US Score an area under the ROC curve (AUC) of 84.13% (95% CI 76.81 – 91.45) was obtained, with a score ≥3, the sensitivity (S) was 82.19% and specificity (E) 80.0%. IBUS-SAS presented an AUC of 84.93% (95% CI 77.98 - 91.87), a result ≥15 granted a S 82.19% and E 80.0%. The SUS-CD index had an AUC of 83.38% (95% CI 75.55 - 91.20), a result ≥1 presented S 82.19% and E 80.0%. Conclusion In our experience, IUS scores (IBUS-SAS, SUS-CD and Simple US Score) show a high sensitivity and specificity in the diagnosis of POR. The three scores had AUC greater than 80%, IBUS-SAS showed slightly higher AUC results.

OP19 Extended mesenterectomy is not superior to mesenteric sparing resection in primary ileocolic resection for Crohn’s Disease in terms of postoperative endoscopic recurrence – results of an international randomised controlled trial

Abstract Background Extended mesenteric resection has recently been proposed to improve clinical outcomes after an ileocolic resection (ICR) for Crohn’s disease. The aim of this study was to analyse the clinical relevance of extended mesenteric resection, up to the level of the ileocolic trunk (intervention group), compared to conventional mesenteric sparing resection (control group) with regard to postoperative outcomes in patients undergoing primary ICR for Crohn’s disease. Methods In an international randomised controlled trial (RCT), patients ≥16 years, were assigned 1:1 to either the intervention- or the control-group. The anastomotic technique was standardised (side-to-side stapled). To demonstrate a relevant difference of 25% in postoperative endoscopic recurrence (defined as a modified Rutgeerts score ≥i2b, according to central reading) at 6 months, a minimum of 62 evaluable patients per arm were required. Secondary outcome parameters were postoperative morbidity, histopathological outcomes and use of Crohn’s medication postoperatively. Results In total, of the 129 included patients, 56 (43.3%) were male with a median age of 36 (IQR 22-55). There were no statistically significant differences in baseline characteristics between the two groups. There was no difference in endoscopic recurrence rates between the two groups: 27/62 (43.5%) in the intervention group and 27/64 (42.2%) in the control group, (p=1.0) Fig 1. Median time until endoscopy was 6 months (IQR 6-7). More patients received postoperative medical prophylaxis in the intervention group (28% vs 14%). In the control group, more patients started medication after endoscopy (intervention group 20% vs control group 27%). This resulted in a similar number of patients in both groups being on Crohn’s medication after six months, 48% in the intervention group and 41% in the control group. There was no significant difference in length of resection specimen (median length colon 7cm; ileum 22.5cm), blood-loss or operative time. Overall, a postoperative complication occurred in 28%, with anastomotic leakage in 5 (3.9%). Conclusion This is the first RCT to present data on the effect of extended mesenteric resection during ICR for Crohn’s disease. The results of this study showed no superiority of extended mesenteric resection with regard to endoscopic recurrence or other perioperative outcomes.

P168 Specialized pro-resolving lipid mediator Resolvin D1 and omega 6 dihomo-γ-linolenic acid are unable to solve inflammation in the creeping fat of patients with severe postoperative recurrence in Crohn's disease

Abstract Background The ω3 derivate resolvin D1 (RvD1), and the ω6 dihomo-γ-linolenic acid (DGLA) prevent collateral damage by overcoming inflammation and enhancing microbial clearance. In Crohn's disease, the mesenteric adipose tissue becomes inflamed and hyperplasies due to transmural lesions and bacterial translocation, developing the so-called creeping fat. This tissue is unable to clear inflammation and has been linked to severer intestinal inflammation and post-operative recurrence (POR). Recently, we have described the presence of DGLA and the increase in the ω6/ω3 ratio together with pro-inflammatory mediators in the creeping fat at surgery. Our aims were study the mechanisms within the inflammatory resolution related to polyunsaturated fatty acids depending on POR severity. Methods Creeping fat samples were obtained in the intestinal resection of Crohn's disease patients and endoscopic POR was evaluated according to the Rutgeerts score: non recurrence (i0+i1; n=18), mild recurrence (i2; n=14) and severe recurrence (i3+i4; n=10). Mesenteric adipose tissue was also collected from patients with colorectal cancer (n=10) and severe obesity (n=11) as reference groups. RvD1 was evaluated by C18/ELISA, lipoprotein lipase (LPL) and hormone-sensitive lipase (HSL) activity by radioassay, and the free fatty acid receptor 1 (FFAR1) expression by qRT-PCR. Results RvD1 was increased in the creeping fat in comparison to the mesenteric adipose tissues of the reference groups (Graphical abstract A) and correlated antagonistically with pro-inflammatory mediators in non-recurrence versus severe recurrence (B). Specifically, factors such as TNF-α, CD14 or IL-18 showed significant positive correlations with RvD1 in severe recurrence while negative in non recurrence. The LPL/HSL ratio indicated greater storage of fatty acids in severe recurrence creeping fats (C), and only in these patients, DGLA negatively correlated with HSL (D) and FFAR1 (E), a receptor that was only detected in Crohn's disease (F). At the same time, this receptor antagonistically correlated with pro-inflammatory mediators such as IL-8 in the creeping fat, positively in non-recurrence and negatively in severe recurrence (G). Conclusion The RvD1 increase suggests a greater production of this factor from ω3, but that would be insufficient to resolve inflammation in severe recurrent creeping fat at surgery time. In this phenotype, HSL activity is linked to a lower presence of DGLA, the only anti-inflammatory ω6. In contrast, the presence of this ligand in severe recurrents seems to reduce the expression of the FFAR1, which acts on the neutrophil function. Thus, immune-inflammation derived from lipid metabolism is antagonistic among the most disparate cases of POR in the creeping fat at surgery.

P841 Exploring Factors Influencing Rutgeerts Score Changes After Ileocecal Resection in Crohn's Disease Patients

Abstract Background Ileocecal resection (ICR) is the most common surgery in Crohn's disease patients with a high risk of postoperative endoscopic and clinical recurrence. The Rutgeerts score is an endoscopic tool used to predict postoperative clinical recurrence and guide therapeutic management. The aim of this study is to identify factors influencing the evolution of this score. Methods We included all Crohn's disease patients undergoing ICR and who had undergone at least two postoperative colonoscopies during the period [2019-2023]. at the Hepato-Gastroenterology Department of MOHAMMED VI university hospital of Oujda,Morocco. Results Forty-six Crohn's disease patients underwent ICR, including 19 females and 27males (sex ratio M/F: 1.4). The mean age of patients was 36 years [26-73], with an average duration of 4 years between diagnosis and ICR. The mean time between surgery and the first follow-up colonoscopy was 10 months, with an average of 18 months between two follow-up colonoscopies. Endoscopic results revealed stability in the Rutgeerts score for 22 patients without the appearance of clinical recurrence signs. Among these patients, 40% were on immunosuppressants (methotrexate n=5, thiopurines n=4), and 60% were on combination therapy. Worsening of the Rutgeerts score was noted in 13 patients, including 30% with perianal manifestations (PAM), 23% with stomas or those who underwent a second surgical intervention during the interval between two colonoscopies, 37% with therapeutic non-adherence, and 10% who stopped treatment. Improvement in the Rutgeerts score was observed in 11 patients, half of whom underwent therapeutic switching or optimization.Identified factors included the use of immunosuppressants or combination therapy, PAM, therapeutic non-adherence, the occurrence of surgery, stomas, therapeutic switching, or optimization. Conclusion In conclusion, our study highlights the complexities in post-ileocecal resection management for Crohn's disease. While stability in Rutgeerts scores was observed in some patients, factors such as perianal manifestations, stomas, and therapeutic non-adherence were associated with score worsening. These findings underscore the need for personalized approaches to optimize postoperative care and inform therapeutic decisions in Crohn's disease patients undergoing ileocecal resection.

OP20 Postoperative endoscopic recurrence after resection of Crohn’s terminal ileitis with Kono-S or side-to-side functional end anastomosis: results of a Multicenter Prospective Randomized Trial

Abstract Background A novel anastomosis (Kono-S) was described in 2003 in Crohn’s disease. Subsequent observations have suggested that this anastomosis is associated with lower endoscopic and surgical recurrence rates. The purpose of this study was to compare the endoscopic recurrence between the Kono-S and the side-to-side functional end anastomosis at 3-6 months after resection of Crohn’s terminal ileitis. Methods This was a prospective multi-center randomized trial conducted at eight international centers. Patients with Crohn’s terminal ileitis requiring elective ileocecal resection were randomized to a Kono-S (Group1) or a side-to-side functional end (Group2) anastomosis (Image1). Patients were discharged on no biologicals. Exclusion criteria included age (<18), pregnancy, recurrent or multisite Crohn’s disease, and need of postoperative treatment with biologicals. Data were collected prior to and during surgery, daily after surgery until discharge, at 30 days post-op, and at 3-6 months colonoscopy. Participating surgeons were instructed in the Kono-S technique through videos. Disease clinical activity was measured by Harvey Bradshaw Index (HBI). Endoscopic remission/recurrence was graded with the modified Rutgeerts score: endoscopic remission was defined as a Rutgeerts score of 0, 1, or 2a, and a Rutgeerts score of 2b or higher was considered a recurrence. All study sites had Institutional Review Board approval, ClinicalTrial.gov # NCT03256240. Results We enrolled 288 Crohn’s patients (50.7% female) with a median age of 34 (18-81). 154 patients were randomized to Group 1 (Kono-S) and 134 to Group 2 (Side-to-Side). 30 days follow-up was completed on 278 (96.9%) patients. The Kono-S group had a higher percentage of past smokers (57 vs.30, p = 0.007) and current smokers (33 vs.12, p = 0.004). The mean operative time was 22 minutes longer in the Kono-S group (154 vs.132 minutes; p = 0.386). There was no mortality. 233 (81%) patients underwent a colonoscopy at 3-6 months. There was no significant difference between the two groups in terms of endoscopic recurrence (p = 0.883) and HBI (p = 0.109) or in recurrence-free survival (Log Rank Mantel-Cox test p = 0.256) (Table 1). On multivariable analysis, current smokers had significantly higher odds for endoscopic recurrence at 3-6 months (OR= 2.80, [95% CI =1.10 - 6.92], p = 0.029). Conclusion Kono-S and Side-to-side anastomoses have similar endoscopic recurrence rates at 3-6 months. Independently of surgical techniques, smokers had a significantly higher rate of endoscopic recurrence at 3-6 months after surgery.

P190 Identification of clinical risk factors for postoperative endoscopic recurrence in Crohn’s disease: a prospective, multicenter cohort study

Abstract Background Further refinement of clinical risk stratification for postoperative endoscopic recurrence in patients with Crohn’s disease is required to identify patients who will benefit from prophylactic therapy. Therefore, we aimed to assess risk factors for endoscopic recurrence in a large prospective, multicenter cohort study. Methods CD patients (≥16 years) scheduled for ileocolic (re-)resection (ICR) and those who underwent an ileocolonoscopy at 6 months following ICR were included. Primary outcome of the study was endoscopic recurrence (modified Rutgeerts’ score ≥ i2b at 6 months). Multivariable logistic regression was performed to identify clinical risk factors. The model included a random effect for the study center to correct for potential correlation between treating center and the outcome. Results In total, 298 patients underwent ICR (79.2% primary ICR, 20.8% re-resection) after a median disease duration of 5.3 years (IQR 1.0 – 12.4). 60.4% of patients were female with a median age at surgery of 34.1 years (IQR 25.7 – 50.5). 67.8% of the patients were exposed to ≥1 biological prior to surgery. Postoperative prophylactic medication (<12 weeks to ICR) was initiated in 85/298 (28.5%) patients; 24.7% immunomodulator, 29.4% anti-TNF, 27.1% combination therapy [immunomodulator with anti-TNF agent], 4.7% vedolizumab, 14.1% ustekinumab. Mean time to postoperative ileocolonoscopy was 6.2 months (SD 1.3). Endoscopic recurrence was diagnosed in 37.9% of the patients. Multivariable logistic regression identified active smoking (adjusted OR [aOR] 3.12; 95% CI 1.63 – 5.98) and penetrating disease behaviour (aOR 1.92; 95% CI 1.04 – 3.57) as risk factors for endoscopic recurrence, whilst ileocolic disease (versus ileal disease; aOR 0.27; 95% CI 0.15 – 0.49) and postoperative prophylactic medication (aOR 0.24; 95% CI 0.12 – 0.47) were identified as protective factors for endoscopic recurrence (Table 1). Conclusion Active smoking and penetrating disease behaviour at time of surgery were identified as risk factors for early postoperative recurrence in Crohn’s disease. Reversely, ileocolic disease at time of surgery and initiation of postoperative prophylactic medication were identified as protective factors for early endoscopic recurrence. Young age at surgery, perianal disease and a prior intestinal resection, included as risk factors in the current international guidelines, were not associated with early endoscopic postoperative recurrence in this large prospective cohort study.

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.

P263 Clinical-Endoscopic Correlation of Postoperative Recurrence in Surgically Treated Crohn's Disease Patients

Abstract Background The majority of patients with Crohn's disease (CD) require surgical intervention at some point in their disease course, particularly ileocolic resection. However, the average rate of clinical postoperative relapse is 30% at 3 years and 60% at 10 years. Endoscopic postoperative recurrence precedes clinical recurrence, highlighting the importance of conducting a colonoscopy 6 to 12 months postoperatively to establish the Rutgeerts score,which predicts the risk of clinical recurrence. The aim of this study is to correlate endoscopic findings with the clinical symptoms of these patients. Methods We retrospectively analyzed clinical symptoms and Rutgeerts scores of Crohn's disease patients who underwent ileocolic resection during the course of their disease, and followed at the Hepato-Gastroenterology Department of MOHAMMED VI university hospital in Oujda, Morocco, during the period [2018-2023] Results Sixty Crohn's disease patients underwent at least one surgical operation during the course of their disease, comprising 25 females and 35 males with a sex ratio (M/F: 1.4). The average age of our patients was 35 years [20-73]. The average time between diagnosis and the first surgery was 4 years. All these patients received postoperative medical treatment before colonoscopy, including azathioprine or methotrexate in 26 patients (43%) and anti-TNF in 34 cases (56%), with an average time of 8 months between surgery and the start of treatment. According to the Montreal classification, the ileocolic form dominated in 88% of cases, with a penetrating phenotype in 40% and a structuring phenotype in 60%. The operative indication was primarily obstructive syndromes in 85% of cases and collections in15%. The average time to perform colonoscopy after surgery was 10 months. During follow-up, 80% of patients were asymptomatic post-surgery, with Rutgeerts scores of I0-I1 in 11(23%) patients, I2 in 13 (27%) cases, I3 in 9 (19%) cases, and I4 in 15 (31%) cases.However, clinical recurrence, characterized by diarrhea, abdominal pain, or Koenig's syndrome, was observed in 20% of patients, with an average postoperative clinical recurrence time of 2 years. The endoscopic findings in these patients revealed Rutgeerts scores of I2 in 4 cases (33%), I3 in 3 cases (25%), and I4 in 5 cases (41%). Conclusion In summary, despite postoperative medical management, the risk of clinical recurrence isnotable. Early postoperative colonoscopy, assessing Rutgeerts scores, proves crucial inpredicting clinical recurrence risk. The observed clinical-endoscopic discordance emphasizes the need for a comprehensive approach to monitoring postoperative outcomes in Crohn's disease.

P205 Histologic image-based ensemble model to identify myenteric plexitis and predict endoscopic postoperative recurrence in Crohn’s disease: a multicentre, retrospective study

Abstract Background Myenteric plexitis is correlated with postoperative recurrence of Crohn’s disease (CD) when relying on traditional statistical methods. However, comprehensive assessment of the myenteric plexus remains challenging. This study aimed to develop and validate a deep learning system to predict postoperative recurrence through automatic screening and identification of features of the muscular layer and myenteric plexus. Methods In this study, we retrospectively reviewed 205 CD patients who underwent bowel resection surgery from 2 hospitals. Patients were divided into a training cohort (n=108), an internal validation cohort (n=47) and an external validation cohort (n=50). A total of 190960 patches from 278 whole-slide images of surgical specimens were analysed using ResNet50, and 6144 features were extracted after transfer learning. Spearman correlation analysis, LASSO logistic regression and the interclass correlation coefficient test were utilized for feature selection. We used five robust algorithms to construct classification models. The performances of the models were evaluated by the area under the receiver operating characteristic curve (AUC) in three cohorts. Results The stacking model achieved satisfactory accuracy in predicting postoperative recurrence of CD in the training cohort (AUC: 0.980; 95% CI 0.960-0.999), internal validation cohort (AUC: 0.908; 95% CI 0.823-0.992), and external validation cohort (AUC: 0.868; 95% CI 0.761-0.975). The accuracy for identifying the severity of myenteric plexitis was 0.833, 0.745, and 0.694 in the training cohort, internal validation cohort and external validation cohort, respectively. Conclusion Our work initially established an interpretable stacking model based on muscular layer and myenteric plexus features extracted from histologic images to identify the severity of myenteric plexitis and predict postoperative recurrence of CD.

Azathioprine plus exclusive enteral nutrition versus azathioprine monotherapy for the prevention of postoperative recurrence in patients with Crohn's disease: an open-label, single-centre, randomised controlled trial.

Azathioprine (AZA) effectively prevents postoperative endoscopic recurrence (ER) in Crohn's disease (CD). However, the efficacy of AZA emerge needs 3 months. Exclusive enteral nutrition (EEN) can maintain remission for CD. The trial investigates whether AZA plus postoperative 3-month EEN is superior to AZA alone in preventing ER of CD. Totally, 84 high-risk CD patients undergoing intestinal resection received AZA alone or AZA plus a 3-month EEN (AZA+EEN) postoperatively. The primary endpoint was the rate of ER at month 12. Secondary endpoint included the rate of ER at month 3, clinical recurrence (CR), CD activity index (CDAI) scores, fecal calprotectin (FC) and CRP. Quality of life were assessed using Short Form-36 (SF-36) and the Inflammatory Bowel Disease Questionnaire (IBDQ). The patients in the AZA+EEN group exhibited significantly lower rates of ER compared to the AZA group at both months 12 (33.3% [13/39] vs 63.2% [24/38], P=0.009) and months 3 (8.6% [3/35] vs 28.1% [9/32], P=0.037) post-surgery. The rates of CR between the two groups at month-3 and month-12 were similar. The CDAI scores, FC, albumin level and CRP were all comparable between the 2 groups. The quality of life was significantly higher in the AZA group than that of the AZA+EEN group at month 3 but became comparable from month 5 to 12 postoperatively. In high-risk CD patients, combining AZA with postoperative 3-month EEN reduces 1-year ER but may temporarily impact quality of life. Further large-scale, long-term studies are warranted.

Major Abdominal Surgery for Pediatric Crohn's Disease in the Anti-TNF Era: 10-Year Analysis of Data From the IBD Registry of Italian Society of Pediatric Gastroenterology, Hepatology, and Nutrition.

The natural history of Crohn's disease (CD) can result in complications requiring surgery. Pediatric data are scarce about major abdominal surgery. The IBD Registry from the Italian Society of Pediatric Gastroenterology, Hepatology, and Nutrition has been active since 2008 and collects data from major pediatric IBD centers in Italy. The aim of the present report was to explore the prevalence of major abdominal surgery among children affected by CD in an era when antitumor necrosis factor (anti-TNF-α) agents were already used so that we might appraise the incidence of surgical-related complications and identify the factors associated with postoperative disease recurrence. We retrospectively analyzed data from patients enrolled in the registry from January 2009 to December 2018. Patients with monogenic IBD and patients undergoing surgery for perianal disease were excluded. In total, 135 of 1245 patients were identified. We report the prevalence of major abdominal surgery of 10.8%. Pediatric surgeons performed the procedure in 54.1% of cases, and a laparoscopic approach was used in 47.4% of surgical procedures. Seventeen patients (12.6%) experienced a total of 21 early postoperative complications, none of which was severe. A laparoscopic approach was the only factor negatively associated with the occurrence of postoperative complications (odds ratio, 0.22; 95% confidence interval, 0.06-0.8; P = .02). Fifty-four (40%) patients experienced postoperative endoscopic recurrence, and 33 (24.4%) of them experienced postoperative clinical recurrence. The postoperative treatment with anti-TNF-α drugs was significantly associated with a reduced risk of endoscopic recurrence (odds ratio, 0.19; 95% confidence interval, 0.05-0.79; P = .02). In our cohort, the overall prevalence of major abdominal surgery was low, as well as the rate of surgical-related complications. Postoperative anti-TNF-α therapy seems be protective against endoscopic recurrence.