Postoperative Crohn's Disease Research Articles

P0310 Intestinal Ultrasound parameters correlate with endoscopic findings in patients with post-operative Crohn’s disease.

Abstract Background In patients with Crohn’s disease (CD) and ileocecal resection, colonoscopy remains the gold-standard for detecting post-operative recurrence (POR). Intestinal ultrasound (IUS) is non-invasive, patient-friendly, with high accuracy for the detection of bowel inflammation. The aim of the present study was to investigate the correlation between post-operative endoscopic findings and those of IUS in patients with CD. Methods We analyzed data from CD patients with ileocecal resection who underwent colonoscopy and IUS for follow up. Post-operative endoscopic recurrence (ER) was defined as Rutgeert’s score (RS)≥i2b. The following IUS parameters were analyzed: bowel wall thickness (BWT), bowel wall stratification (BWS), modified Limberg score for the assessment of bowel wall hyperemia (BWH) and neo-terminal ileum peristalsis. Linear and binary logistic regressions were used to identify associations between RS and IUS parameters. SPSS-23 was used for the statistical analysis with a threshold of P=0.05 for statistical significance. Results In total, 44 patients [29 male, median age (SD): 40 (14.7) years] underwent IUS 42 [2-126] months following ileocecal resection. Thirty-eight (86%) patients were on treatment [infliximab 10 (23%), adalimumab 9 (21%), ustekinumab 11 (25%), vedolizumab 4 (9%), ozanimod 1 (2%) azathioprine 1 (2%), methotrexate 1 (2%)] and 7 (16%) patients were on no treatment. Endoscopic recurrence was detected in 52% of patients. Higher RS was associated with increased BWT, absence of peristalsis in the neo-TI and loss of BWS (P=0.007, P=0.001 and P=0.028 respectively). In multivariate analysis a higher RS was independently associated with the absence of peristalsis in the neo-terminal ileum (P=0.019). A tendency for a positive correlation between RS and ΒWT (P = 0.071) was also observed. RS≥i2b was significantly correlated with loss of BWS (P=0.045), absence of peristalsis (P=0.027) and a tendency was observed with BWT(P=0.081). RS≥i3 was significantly correlated with absence of peristalsis in the neo-TI (P= 0.001), BWT>3mm (P= 0.041), while a tendency was observed with modified Limberg score≥2 (P= 0.082). Conclusion IUS parameters correlate with RS in patients with post-operative CD. IUS may be a valuable monitoring tool for the assessment of POR in CD. Larger prospective studies are needed to determine cut-off values of sonographic parameters that may accurately predict post-operative recurrence of CD.

P0888 Time-trends in the management of postoperative Crohn’s Disease and its impact on long-term surgical recurrence. Data from the ENEIDA registry

Abstract Background Anti-TNF availability has been associated with a decrease of first intestinal resections in patients with Crohn’s Disease (CD). However, few studies have evaluated the impact of the availability of biological therapies in the medical management of postoperative CD and its long-term outcomes. We aimed to assess the time trends in the strategies for the management of CD in the postoperative setting after a first intestinal resection and the rate of second surgeries (surgical postoperative recurrence –sPOR-) through the last three decades. Methods Adult patients with CD who underwent a first ileocolic resection with ileocolic anastomosis between 1990 and 2020 and with at least one year of clinical follow-up, were identified from the Spanish ENEIDA registry. Patients in whom ileocolic resection was due to cancer were excluded. Patients were grouped by the date of the first surgery (before biologicals era -BB- 1990-2000; early biological era -EB- 2001-2010; widespread biological era -WB- 2011-2020). Medical prevention for POR was defined as any immunomodulator or biological agent that was started within the first 6 months after the index surgery and maintained for at least 3 months. Treatment for POR was defined as any immunomodulator or biological that was started at least 6 months after index surgery. Surgical POR was defined as a second intestinal resection at least 6 months after the index surgery. Results 4,890 patients who were followed-up for a median of 125 months (IQR 70-204), were included. Baseline characteristics of each cohort are shown in Table 1. A significant increase in the proportion of patients starting medical prevention of POR with thiopurines and biologicals was observed over time as well as in the proportion of patients starting treatment with biologicals. The cumulative incidence of sPOR significantly decreased in both EB and WB cohorts (second surgery-free survival at 3, 5 and 10 years: BB 96%, 92%, 83%; EB 98%, 96%, 90%; WB 98%, 97%, 91%; P=<0.001). In the IPTW propensity model to weight differences for POR risk factors, both biologicals cohorts remained associated with a lower risk of sPOR. Conclusion In the last three decades, we observed a significant increase in the use of medical prevention for POR together with a significant increase in using biologicals to treat POR. These changes resulted in a significant decrease in the cumulative incidence of a second intestinal resection in the long-term.

P1311 Mucosal Microbiome Signatures Associated with Postoperative Endoscopic Recurrence in Paediatric Crohn’s Disease

Abstract Background Following ileocecal resection (ICR) for Crohn’s disease (CD), recurrence is frequent even in the biologic era. Gut microbiota is involved in this setting and a few adult studies have suggested that bacterial recolonization after surgery may predict recurrence. Given the inherent risk of postoperative recurrence associated with age and disease duration, studies investigating the role of the gut microbiota in predicting relapse in children undergoing ICR appears critical. We aimed to identify changes in the mucosal microbiome associated with, and predictive of, endoscopic CD recurrence within the first year post-ICR in a paediatric population. Methods Microbiota composition (16S rDNA sequencing) was assessed from ileal and colonic mucosa at the time of ICR and later during endoscopic evaluation from above and below the surgical anastomosis in 33 patients (26 with paired samples) prospectively recruited at a tertiary care paediatric IBD center. Results The study included 33 children (mean age 16±2.7 years) undergoing ICR. At the time of ileo-colonoscopy, 9 (35%) patients had endoscopic recurrence (Rutgeerts’ score≥ i2). ICR strongly modified the gut mucosal microbiota composition with significant changes in β-diversity (R2= 0.03, PERMANOVA test, p=0.01). Bacterial recolonization post-ICR differed according to recurrence status (Figure 1). Post-operatively, recurrence was associated with an increase in Fusobacterium, Dialister genera and in members of the Lachnospiraceae family, and a decrease in Faecalibacterium, Lactobacillus genera and members of the Streptococcaceae family. Microbiota colonizing the neoterminal ileum and subanastomotic colon differed in children with recurrence and showed, compared to remission, elevated and reduced bacterial abundance of the Enterobacter (q=0.1) and Ruminococcaceae (q=0.05) families in colonic samples respectively while the ileal mucosa exhibited profound depletion in Faecalibacterium (q=0.01). Postoperative colonic mucosal relative abundance of Enterobacteriaceae (q=0.06) and Ruminococcaceae (q=0.06) correlated positively and negatively with length of intestinal resection. At the time of surgery, several bacterial taxa able to predict relapse were identified (Figure 2). Conclusion Predicting postoperative CD relapse remains challenging, although several clinical risk factors of recurrence have been identified. Our study demonstrates that bacterial recolonization following ICR might pave the way towards remission or recurrence. Our results highlight, for the first time in a paediatric population, target species that may help clinicians to better define patients at risk of relapse and allow precise modulations of the overall microbial ecosystem towards remission pattern.

P0924 Efficacy and Safety Assessment of Ustekinumab in Postoperative Crohn’s Disease Patients in China

Abstract Background Crohn’s disease (CD) poses a significant risk of postoperative recurrence (POR), complicating management, and data on the use of Ustekinumab (UST) in postoperative CD patients in China is limited. This study evaluated the efficacy and safety of UST in preventing POR. Methods This multicenter, retrospective observational study involved postoperative CD patients from four Chinese tertiary hospitals, all of whom had at least two high-risk recurrence factors. Patients who failed anti-TNF-α treatments or Vedolizumab switched to UST as non-first-line therapy, while others received UST as first-line treatment at least two weeks post-surgery. Efficacy was evaluated using endoscopic success (Rutgeerts score) and clinical disease activity (Harvey-Bradshaw Index [HBI]), with safety determined by adverse events after a minimum follow-up of 24 weeks. Results This study included 53 patients with a mean age of 36.8 years. Significant improvement in the Rutgeerts score was observed (p < 0.001). The remission rate (i0) increased from 0.0% to 32.1% post-treatment. Notable changes were seen in i1 (from 5.7% to 32.1%) and i2 (from 49.1% to 28.3%), while severe disease cases (i3 and i4) declined significantly. Overall, the endoscopic success rate was 83.0%. Similarly, the HBI score significantly improved (mean ± SD: 6.1 ± 2.5 before vs. 2.4 ± 1.7 after, p < 0.001). The median HBI decreased from 6.0 to 2.0, with remission rates rising from 18.9% to 90.6%, while active disease cases fell from 81.1% to 9.4% (p < 0.001). The percent of 90.3 in the first-line group experienced a decrease in their Rutgeerts score, compared to 72.7% in the second-line group, though this difference was also not statistically significant (p = 0.093). A significant difference was noted in HBI scores (p = 0.016), with the first-line group’s mean at 1.9 ± 1.3 being significantly lower than the second-line group’s 3.1 ± 1.9. The median HBI followed this trend, with values of 2.0 for the first-line and 3.0 for the second-line group. The mean BMI increased from 19.9 ± 3.8 to 21.1 ± 3.7, though not significantly (p = 0.078). Nutritional status improved, as indicated by increased mean albumin (41.3 ± 15.2 vs. 43.7 ± 15.3, P = 0.043) and hemoglobin levels (116.6 ± 24.9 vs. 125.9 ± 23.9, P = 0.019). Only one adverse event, secondary kidney function impairment, was reported. Conclusion UST exhibited significant efficacy in preventing POR of CD with a favorable safety profile, whether used as a first-line or non-first-line treatment. Our research provided essential evidence from an Eastern population regarding the effectiveness and safety of UST in postoperative CD patients. References Torres J, Bonovas S, Doherty G, et al. ECCO Guidelines on Therapeutics in Crohn’s Disease: Medical Treatment. J Crohns Colitis. 2020. 14(1): 4-22.

Vedolizumab prophylaxis against postoperative Crohn's disease recurrence.

Vedolizumab prophylaxis against postoperative Crohn's disease recurrence.

The Effect of Colesevelam on the Microbiome in Postoperative Crohn's Disease.

While surgery plays a pivotal role in the management of ileal Crohn's disease, the risk of endoscopic recurrence following an ileocaecal resection can be greater than 65% within 12 months of surgery. More than 90% of patients with Crohn's disease have a concomitant diagnosis of bile acid diarrhea following an ileal resection. This pilot study aimed to assess whether the use of bile acid sequestrants in patients with Crohn's disease who have undergone a primary terminal ileal resection with concomitant bile acid diarrhea can alter the microbiome and prevent disease recurrence. Patients with Crohn's disease who underwent a primary terminal ileal resection and had symptoms of diarrhea within 1-3 months of surgery underwent 75SeHCAT testing for bile acid diarrhea. If positive (75SeHCAT ≤ 15%), patients were treated with colesevelam and stool samples were collected at 4 weeks, 8 weeks, and 6-12 months posttreatment. If negative (75SeHCAT > 15%), treatment was not given and were reviewed in the clinic as per local guidelines. All patients underwent a 6-12 month postoperative colonoscopy where further stool samples and mucosal biopsies were taken. Disease activity was established using the endoscopic Rutgeert's score, with disease remission defined as Rutgeert's score <i2 and disease recurrence ≥i2. 16S ribosomal RNA gene analysis was undertaken for the collected fecal and mucosal samples to assess α/β-diversity and microbial composition. A total of 14 patients who completed the study, 10 of whom had a 75SeHCAT positive diagnosis of bile acid diarrhea and were started on treatment with colesevelam. Four patients did not require treatment as 3 were asymptomatic and 1 had a negative 75SeHCAT scan. Three of the fourteen patients had disease recurrence at their 6-12 month postoperative colonoscopy assessment, of which 1 patient was taking colesevelam and 2 patients were not taking colesevelam. A total of 44 fecal samples and 44 mucosal biopsies underwent 16S ribosomal RNA gene analysis to assess α/β-diversity and microbial composition. In the colesevelam treated patients there was no significant difference in α/β-diversity pre- and posttreatment. Pretreatment, the 3 most abundant bacterial classes in all patients were Bacteroidia, Clostridia, and Gammaproteobacteria. Following 6-12 months of treatment, out of the 9 patients on colesevelam, 5/9 (55.6%) had a reduction in Bacteroidia, 9/9 (100%) had an increase in Clostridia, and 7/9 (77.8%) had a reduction in Gammaproteobacteria. Of the 2 patients not given colesevelam, one showed a reduction in Bacteroidia, increase in Clostridia and a reduction in Gammaproteobacteria. This small pilot study demonstrated that patients who were given colesevelam, were more likely to be in disease remission at their 6-12 months colonoscopy review compared with those not treated. Furthermore, treatment with colesevelam may have a role in altering the microbiome to help maintain remission states in postoperative Crohn's disease. Larger mechanistic studies are now needed to confirm these findings and demonstrate statistical significance as well as investigate whether this benefit may be present even in those patients with 75SeHCAT negative disease.

Risk Factors for Recurrence of Crohn's Disease After Ileocecal Resection and Management Strategies

IntroductionPediatric patients with ileocecal Crohn's Disease (CD) refractory to medical management frequently require ileocecectomy. However, risk factors for post-operative ileocecal recurrence and appropriate management strategies are poorly defined in the pediatric literature in the biologic era. MethodsWe queried our institutional database from 1/1/2012–12/31/2022 for patients aged 1–21 who underwent primary ileocecectomy for CD. We analyzed baseline characteristics, operative details, medical management, recurrence patterns, and management patterns. ResultsWe identified 208 patients who underwent primary ileocecal resection, of which 66 (23%) demonstrated endoscopic recurrence at 2.1 ± 0.5 years and 28 (13%) developed clinical recurrence at 2.5 ± 0.8 years. Recurrence was at the surgical anastomosis in 43 (21%). Before surgery, 138 (66%) were treated with a biologic, of which 25 (18%) were transitioned to a second line biologic pre-operatively. Requiring a separate intervention for perianal or intestinal disease increased the odds of recurrence on multivariable analysis, as did requiring a second line biologic. Of those with endoscopic recurrence, most [62/66 (94%)] were successfully managed with medical optimization alone. Only four (6.7%) required procedural intervention with two being managed with endoscopic balloon dilation and two requiring repeat resection and re-anastomosis. Median follow up was 2.6 years [IQR 1.2–4.5]. ConclusionRequiring separate interventions for perianal or intestinal disease and demonstrating disease difficult to medically control may increase the risk of recurrent post-operative ileocecal CD. Such patients should be closely surveilled for endoscopic recurrence and may warrant more aggressive medical regimens. Recurrence can typically be managed medically with few patients requiring procedural intervention. Level of EvidenceIII.

Role of Intestinal Ultrasound for IBD Care: A Practical Approach.

Intestinal ultrasound (IUS) has recently become the imaging technique of choice for patients with different types of intestinal inflammation. IUS has a high sensitivity, specificity, positive predictive value, and negative predictive value when diagnosing Crohn's disease or ulcerative colitis. Further, it is now the preferred imaging modality for routine IBD reevaluations because of its non-invasiveness, cost-effectiveness, availability (at least in Europe), and reproducibility in all age groups. However, the clinical success of IUS requires IUS training for doctors and technicians who perform IUS with a standardised description of ultrasound findings of the terminal ileum and entire colon. Complications such as abscess formation, fistulae, and stenosis can be detected by either conventional IUS or contrast-enhanced ultrasound (CEUS). Lately, several disease activity scores have been proposed for Crohn's disease, postoperative Crohn's disease, and ulcerative colitis both in adults (including elderly) and in children. IUS was successfully used in randomised clinical trials in order to measure the treatment response. Therefore, IUS now plays a central role in clinical decision making.

Small bowel pyloric metaplasia is associated with lower rates of earlier recurrence of Crohn's disease after resection

Recurrence within one or two years is common after Crohn's disease (CD) resection. In this study, we seek to identify histologic features in CD resections that may predict earlier (≤18 months) recurrence to potentially guide post-operative management. A single-institution, retrospective review was performed on patients with first-time CD bowel resection specimens (2002–2007). Patient demographics and CD course were also documented. Slides were reviewed for inflammatory distribution and composition, small bowel (SB) pyloric metaplasia (PM), and presence and characteristics of submucosal fibrosis and granulomas. In our cohort, 14 of 41 patients experienced earlier clinical or endoscopic recurrence after initial resection. In the 38 patients who underwent SB resection (3 were colon only), PM was less common in those with earlier recurrence (6/12 [50%]) compared to those with later (>18 months) or no known recurrence (22/26 [85%]) (P = 0.045). PM was present even in patients with <1 year of known CD. Additionally, therapy with anti-tumor necrosis factor (TNF) prior to surgery was more common in earlier recurrence patients (7/14 [50%]) than later or no recurrence patients (4/27 [15%]) (P = 0.026). There was no significant difference in age, sex, smoking status, duration of CD, post-operative CD medication, distribution or features of inflammation, granulomas, or fibrosis. Overall, our results indicate that SB PM and pre-surgical anti-TNF therapy are possible helpful clinicopathologic features to evaluate for recurrence risk.

Histologic Activity From Neoterminal Ileal Biopsies in Patients With Crohn's Disease in Endoscopic Remission is Associated With Postoperative Recurrence.

Following ileocolic resection (ICR), the clinical importance and prognostic implications of histologic activity on biopsies in Crohn's disease (CD) patients with endoscopic remission are not well defined. The aim of this study was to determine if histologic activity in patients with endoscopic remission is associated with future risk of endoscopic and/or radiologic postoperative recurrence (POR). In this multicenter retrospective cohort study, adult patients with CD who underwent ICR between 2009 and 2020 with endoscopic biopsies of ileal mucosa from Rutgeerts i0 on index colonoscopy were included. The composite rate of endoscopic (Rutgeerts score ≥i2b) and radiologic (active inflammation on imaging) recurrence was compared in patients with and without histologic activity using a Kaplan-Meier survival analysis. A multivariable Cox proportional hazard regression model including clinically relevant risk factors of POR, postoperative biologic prophylaxis, and histology activity was designed. A total of 113 patients with i0 disease on index colonoscopy after ICR were included. Of these, 42% had histologic activity. Time to POR was significantly earlier in the histologically active versus normal group ( P = 0.04). After adjusting for clinical risk factors of POR, histologic activity (HR 2.37, 95% CI 1.17-4.79; P = 0.02) and active smoking (HR 2.54, 95% CI 1.02-6.33; P = 0.05) were independently associated with subsequent composite POR risk. In patients with postoperative CD, histologic activity despite complete endoscopic remission is associated with composite, endoscopic, and radiographic recurrence. Further understanding of the role of histologic activity in patients with Rutgeerts i0 disease may provide a novel target to reduce disease recurrence in this population.

Efficacy of Ustekinumab and Vedolizumab Among Postoperative Crohn's Disease Patients as Postoperative Prophylaxis and Rescue Therapy: Real-world Data.

Almost half of patients with Crohn's disease (CD) require bowel surgeries in their lifetime. Due to the high risk of postoperative disease recurrence and high rate of previous antitumor necrosis factor (anti-TNF) failure, often alternative therapy options such as ustekinumab (UST) and vedolizumab (VDZ) are used. We aimed to evaluate the efficacy of UST and VDZ among postoperative CD patients as postoperative prophylaxis and rescue therapy. Consented CD patients who underwent initial ileocecal resection and were treated with UST and VDZ were included in this study. Demographics, clinical characteristics, health care utilization, endoscopy scores, and surgery outcomes were collected. Postoperative early CD recurrence was defined as a Rutgeerts endoscopic score ≥i2 within the first 2 years. The rescue therapy group was defined as patients who received either UST or VDZ after having Rutgeerts endoscopic score ≥i2 postoperatively. During 2009 to 2019, 98 CD patients were treated with UST or VDZ postoperatively. Postoperative early recurrence rates were 5% (n = 1 out of 20) and 6% (1 out of 15) for the UST and VDZ groups, respectively. Two patients from the UST group and 1 patient from the VDZ group required bowel surgery during follow-up with median drug exposure of 51 (95% confidence interval [CI], 29-61) and 30 (95% CI, 14-63) months, respectively; 55% and 69% of patients had at least 1 point of improvement on postoperative endoscopic Rutgeerts score, respectively, for UST and VDZ. Only 3 out of 40 and 1 out of 23 patients required bowel surgery during follow-up while receiving UST and VDZ as rescue therapy. Both UST and VDZ were effective as postoperative therapies either as prophylaxis or rescue therapy.

After Surgically Induced Remission, Ileal and Colonic Mucosa-Associated Microbiota Predicts Crohn’s Disease Recurrence

Investigating the tissue-associated microbiota after surgically induced remission may help to understand the mechanisms initiating intestinal inflammation in Crohn's disease. Patients with Crohn's disease undergoing ileocolic resection were prospectively recruited in 6 academic centers. Biopsy samples from the neoterminal ileum, colon, and rectosigmoid were obtained from colonoscopies performed after surgery. Microbial DNA was extracted for 16S rRNA gene sequencing. Microbial diversity and taxonomic differential relative abundance were analyzed. A random forest model was applied to analyze the performance of clinical and microbial features to predict recurrence. A Rutgeerts score ≥i2 was deemed as endoscopic recurrence. A total of 349 postoperative colonoscopies and 944 biopsy samples from 262 patients with Crohn's disease were analyzed. Ileal inflammation accounted for most of the explained variance of the ileal and colonic mucosa-associated microbiota. Samples obtained from 97 patients who were in surgically induced remission at first postoperative colonoscopy who went on to develop endoscopic recurrence at second colonoscopy showed lower diversity and microbial deviations when compared with patients who remained in endoscopic remission. Depletion of genus Anaerostipes and increase of several genera from class Gammaproteobacteria at the 3 biopsy sites increase the risk of further recurrence. Gut microbiome was able to predict future recurrence better than clinical features. Ileal and colonic mucosa-associated microbiome deviations precede development of new-onset ileal inflammation after surgically induced remission and show good predictive performance for future recurrence. These findings suggest that targeted microbial modulation is a plausible modality to prevent postoperative Crohn's disease recurrence.

Postoperative Crohn's Disease Recurrence Risk and Optimal Biologic Timing After Temporary Diversion Following Ileocolic Resection.

Postoperative recurrence of Crohn's disease (CD) is common. While most patients undergo resection with undiverted anastomosis (UA), some individuals also have creation of an intended temporary diversion (ITD) with an ileostomy followed by ostomy takedown (OT) due to increased risk of anastomotic complications. We assessed the association of diversion with subsequent CD recurrence risk and the influence of biologic prophylaxis timing to prevent recurrence in this population. This was a retrospective cohort study of CD patients who underwent ileocolic resection between 2009 and 2020 at a large quaternary health system. Patients were grouped by continuity status after index resection (primary anastomosis or ITD). The outcomes of the study were radiographic, endoscopic, and surgical recurrence as well as composite recurrence postoperatively (after OT in the ITD group). Propensity score-weighted matching was performed based on risk factors for diversion and recurrence. Multivariable regression and a Cox proportional hazards model adjusting for recurrence risk factors were used to assess association with outcomes. Subgroup analysis in the ITD group was performed to assess the impact of biologic timing relative to OT (no biologic, biologic before OT, after OT) on composite recurrence. A total of 793 CD patients were included (mean age 38 years, body mass index 23.7kg/m2, 52% female, 23% active smoker, 50% penetrating disease). Primary anastomosiswas performed in 67.5% (n = 535) and ITD in 32.5% (n = 258; 79% loop, 21% end) of patients. Diverted patients were more likely to have been males and to have had penetrating and perianal disease, prior biologic use, lower body mass index, and lower preoperative hemoglobin and albumin (all P < .01). After a median follow-up of 44 months, postoperative recurrence was identified in 83.3% patients (radiographic 40.4%, endoscopic 39.5%, surgical 13.3%). After propensity score matching and adjusting for recurrence risk factors, no significant differences were seen between continuity groups in radiographic (adjusted hazard ratio [aHR], 1.32; 95% confidence interval [CI], 0.91-1.91) or endoscopic recurrence (aHR, 1.196; 95% CI, 0.84-1.73), but an increased risk of surgical recurrence was noted in the ITD group (aHR, 1.61; 95% CI, 1.02-2.54). Most (56.1%) ITD patients started biologic prophylaxis after OT, 11.4% before OT, and 32.4% had no postoperative biologic prophylaxis. Biologic prophylaxis in ITD was associated with younger age (P < .001), perianal disease (P = .04), and prior biologic use (P < .001) but not in recurrence (P = .12). Despite higher rates of objective disease activity identified before OT, biologic exposure before OT was not associated with a significant reduction in composite post-OT recurrence compared with starting a biologic after OT (52% vs 70.7%; P = 0.09). Diversion of an ileocolic resection is not consistently associated with a risk of postoperative recurrence and should be performed when clinically appropriate. Patients requiring diversion at time of ileocolic resection are at high risk for recurrence, and biologic initiation prior to stoma reversal may be considered.

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 &amp;lt;0.001), had fewer postoperative complications (p 0.01) and more often had ICA lesions (p &amp;lt;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 &amp;gt;46% of inflamed clusters’ composition and &amp;lt;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 &amp;gt;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.