Stricture Research Articles

A successful case of urinary rediversion from a complicated cutaneous ureterostomy to a new ileal conduit

IntroductionA ureteral stricture often develops after a cutaneous ureterostomy and can lead to complicated situations in some cases.Case presentationWe performed surgery on a 54‐year‐old man who required routine replacement of a ureteral stent every 2 weeks after cystectomy. We surgically converted his cutaneous ureterostomy into a new ileal conduit. Following the surgery, his ureteral stent was removed, allowing him to resume his social activities.ConclusionWe reported the possibility of urinary rediversion as a treatment option for a complicated cutaneous ureterostomy patient.

Urogenital Tuberculosis: A Narrative Review and recommendations for diagnosis and treatment.

to review the more relevant aspects of urogenital tuberculosis (UGT) and make recommendations about the diagnosis and treatment. a literature review was conducted in the Pubmed, Embase and Scielo databases in search of studies on UGT in the past 60 years. A narrative review was performed concerning six topics of UGT diagnosis and treatment. Recommendations were made supported on degrees of evidence according to the modified GRADE system. UGT suspicion occurs in persistent hematuria or pollakiuria with sterile pyuria; stenosis and/or thickening of the urinary tract; or chronic prostatitis or epididymitis. Urinary bacteriological tests have low sensitivity, and a negative test does not rule out UGT diagnosis. In ureteral stenosis, a double-J catheter or nephrostomy should be used early (up to 1 month) during pharmacological treatment and in single less than 2 cm stenosis endoscopic treatment may be attempted. Bladder augmentation with ileum, sigmoid or ileocecal segments should be performed when the contracted bladder capacity is less than 100 mL. Spontaneous voiding occurs in most patients after bladder augmentation. The diagnosis of UGT depends on a high degree of suspicion based on non-specific symptoms and radiological findings. Urinary bacteriological tests have low sensitivity, but even in the absence of diagnostic confirmation, treatment can be carried out through a combination of drugs for a period of six months. In the presence of ureteral stenosis or contracted bladder, complex but well stablished reconstruction procedures are necessary.

Laparoscopic ureteral obstruction modelling for training purposes

Abstract Introduction Pyeloplasty is a surgical technique used to treat hydronephrosis, which is caused by ureteral stenosis or obstruction. It is essential for healthcare professionals to undergo training courses to acquire and strengthen their skills in laparoscopic surgery, thus providing patients with the benefits of minimally invasive procedures. The aim of this study is to create experimental models of ureteral obstruction and subsequently use them to train healthcare professionals in the surgical technique of pyeloplasty. Methods Sixteen Large White swine, each weighing 35±5 kg, were used as experimental models. Surgery was performed with the animals positioned in right lateral decubitus via a laparoscopic approach. Once the ureter was located, it was dissected proximally to the kidney, and obstruction was created using a 2/0 non-absorbable silk ligature. Results Ten days after surgery, all models had survived, and 14 of the 16 models exhibited hydronephrosis and renal pelvis dilatation prior to obstruction by silk ligation. Conclusion Ureteral stricture generated by silk ligation is an effective method for creating experimental models of ureteral obstruction. Surgical training with these models enables healthcare professionals to develop the skills necessary to master minimally invasive surgical techniques, such as pyeloplasty.

P0877 Machine Learning and Mendelian Randomization Analysis for Predicting Endoscopic Restenosis in Patients with Crohn's Disease after Endoscopic Balloon Dilation

Abstract Background Endoscopic balloon dilation (EBD) is a safe and effective procedure for treating stenosis in patients with Crohn's disease (CD). This study aimed to evaluate factors associated with endoscopic restenosis after EBD and construct a prognostic model. Methods We retrospectively collected and analyzed data on patients receiving EBD treatment at the Sixth Affiliated Hospital of Sun Yat-sen University from 2013 to 2024. Seven machine learning (ML) algorithms were used to construct a prognostic model. And explore potential biomarkers of intestinal stricture using Mendelian randomization (MR). Results A total of 135 patients were included in the statistical analysis. 53% occurred endoscopic restenosis, with an average restenosis time of 183 days. COX and logistic regression analysis showed that 4 features including ever-use glucocorticoids, stenosis position, technical success, and albumin level were associated with restenosis risk. When comparing different ML models, CoxPH and LASSO models performed better on various evaluation metrics, including C-index which was greater than 0.7 in the train and test set. Based on SHapley Additive exPlanations (SHAP), stenosis position, balloon diameter, and albumin level were identified as the top 3 important features associated with prognosis. Two-sample MR analysis identified 50 potential biomarkers of intestinal stricture. However, two-step MR analysis did not find any mediating effect between CD and intestinal stricture. Conclusion ML-based prognostic models have good predictive performance and can accurately assess the risk of endoscopic restenosis after EBD treatment. However, MR analysis did not identify reliable stenosis-related biomarkers in CD.

P0388 Can intestinal ultrasound guide us in the treatment of inflammatory bowel disease?

Abstract Background Intestinal Ultrasonography (IUS) is a useful method for monitoring inflammatory bowel disease. The role of Shear Wave Elastography (SWE) and the relationship with other parameters indicating activity are not yet well understood. Methods The aim was to describe the ultrasound characteristics observed in a cohort of patients with Crohn’s disease (CD) and the changes in therapeutic attitude derived from the results of this imaging test. To evaluate the usefulness of SWE in patients with intestinal strictures to detect fibrosis in comparison with analytical and ultrasound parameters of inflammatory activity. We conducted a single-center, retrospective, observational study of a baseline study including IUS examinations performed in CD patients between May 2022 and February 2023. Results We included 63 IUS in CD patients (60.9% male; mean age 43 ± 17 years). The mean HBI-score was 2.77 (± 2.6). A change in therapeutic approach was made in 32.8% of cases following IUS. Stricture was found in 22 IUS (34.9%), with a mean length of 5.6 ± 2.59 cm. Fat wrapping was observed in 40.9% of cases, and loss of wall stratification in 9.1%. Median SWE of the stricture was 9.05. Calprotectin is directly related to the Limberg scale (p<0.001) and indirectly with the SWE value (p<0.05). Inverse correlation between Limberg scale and SWE value (p<0.05) was observed. Conclusion intestinal ultrasonography facilitates a proactive monitoring in CD because immediate changes in therapeutic approach can be made. The combination of the Limberg scale and the SWE value allow the definition of intestinal strictures. Comparative studies are needed to clarify the usefulness in predicting the degree of fibrosis.

P0196 Metabolic dysregulation in Crohn’s disease fibrosis: Targeting WISP1 to restore ECM homeostasis

Abstract Background In patients with Crohn’s disease (CD), homeostasis of the extracellular matrix (ECM) is significantly disrupted, frequently leading to severe complications such as intestinal stenosis. The maintenance of organ functionality depends on a delicate balance between inflammatory mediators, ECM production, and degradation processes. However, these mechanisms remain poorly understood. This study investigates the dynamic interplay between ECM homeostasis and metabolic pathways in CD, providing novel insights into their role in disease pathogenesis and potential therapeutic intervention. Methods Bulk RNA sequencing was performed to compare fibrotic and non-fibrotic intestinal tissues from CD patients undergoing ileocecal resection, aiming to identify key metabolic and ECM-related pathways. Primary matrix-producing fibroblasts were studied in 2D cultures and spheroids to characterize their metabolic activity, with a focus on fatty acid oxidation (FAO) and glycolysis through gene and protein analysis, metabolic assays, and fatty acid profiling (GC-FID). Chronic intestinal fibrosis was modelled in vivo using dextran sodium sulfate (DSS)-treated mice, allowing therapeutic evaluation of WISP1 neutralisation. The in vivo model was characterized using histological and clinical scoring, as well as gene and protein expression analysis. Results Gene set enrichment analysis revealed increased WNT signaling coupled with a reduction in fatty acid metabolism. Additionally, fibrotic tissue exhibited elevated levels of oleic acid and palmitate, indicative of increased lipid accumulation. WISP1, a WNT mediator, was identified as an adipokine and a key regulator of the metabolic shift from fatty acid oxidation to glycolysis. The disruption of FAO-related genes, including PPARγ, CPT1A, CPT2, and ACOX1, demonstrated reciprocal effects on fibroblast activity: pharmacological inhibition of FAO increased matrix production by fibroblasts, whereas activation of FAO via the PPARα agonist fenofibrate induced a catabolic fibroblast phenotype. This phenotype was characterized by suppressed ECM expression and enhanced ECM degradation via MMP1. Importantly, therapeutic neutralization of WISP1 significantly reduced fibrosis in a chronic DSS-induced colitis model. Conclusion This study presents a novel therapeutic strategy for managing fibrosis in Crohn’s disease. By pharmacologically neutralizing WISP1, this approach aims to correct the underlying metabolic dysfunction, thereby restoring metabolic balance and ECM homeostasis.

P0135 Effect of human recombinant IL-33 on fibrosis markers in colonic fibroblasts

Abstract Background IBD is frequently complicated by intestinal fibrosis and strictures formation, occurring in more than 50% of Crohn’s disease (CD) and 5% of ulcerative colitis. Intestinal fibrosis leads to surgery in CD and strictures frequently recur leading to repeated surgeries1. There is currently no specific therapy to prevent or inhibit intestinal fibrosis and this therefore constitutes a major treatment challenge. Intestinal fibrosis is characterized by excessive deposition of extracellular matrix (ECM) synthesized by intestinal myofibroblasts1. Interleukin-33 (IL-33) is a pleiotropic nuclear cytokine involved in immunoregulation and tissue repair2. Following cellular injury, IL-33 is released by epithelial, endothelial or fibroblast cells. Binding to the ST2 (suppressor of tumorigenicity 2) receptor, it induces translocation of the transcription factor NF-□□□□B, which regulates the expression of pro-inflammatory genes2. IBD patients have increased colonic expression of IL-33 and ST2 in epithelial cells compared to control patients3. Neutralization of IL-33 enables the repair of lung epithelial cells by limiting the release of pro-inflammatory cytokines such as IL-6, IL-8 and TNF-α in a mouse model of pulmonary epithelial lesions4. We hypothesized that IL-33 may be involved in IBD-associated intestinal fibrosis. We therefore aimed to understand the role of IL-33 in a human colonic fibroblast cell line (CCD-18Co). Methods First, we measured IL-33 and ST2 mRNA expression in CCD-18Co in response to TGF-ß1 (10 ng/mL) and/or TNF-ɑ (100 ng/mL) for 24h. Then, CCD-18Co were induced by increasing doses of IL-33 treatment (10, 50, 100 ng/mL) for 24h and inflammatory and fibrosis markers were measured. Results TGF-ß1 significantly induced mRNA levels encoding ECM-associated proteins such as α-SMA (***p<0.001) or COL1A1 (*p<0.05, Figure 1).Treatment with TGF-ß1 and/or TNF-α had no effect on the expression of mRNAs encoding IL-33 and ST2 in CCD-18Co in our experimental conditions. IL-33 treatment significantly increased mRNA levels for IL-1ß and ECM-associated proteins (COL3A1, CTGF and VIM) (*p<0.05, Figure 1) in CCD-18Co but these effects are abolished in presence of TGF-ß1 and/or TNF-α treatment. Conclusion Treatment with TGF-ß1 and/or TNF-α had no significative impact on IL-33 mRNA levels in the CCD-18Co in our experimental conditions. IL-33 treatment increased ECM-associated proteins in CCD-18Co line under basal conditions but not in TGF-ß1 and/or TNF-α conditions.

P0188 The Role and Mechanism of Ephrin B2 in Crohn’s Disease-Associated Intestinal Fibrosis

Abstract Background Crohn’s disease (CD) is a chronic inflammatory bowel condition characterized by transmural inflammation that can lead to intestinal fibrosis and strictures. This study aimed to investigate the role of Ephrin B2, a member of the ephrin family, in the pathogenesis of CD-associated intestinal fibrosis.The primary objective of this study was to elucidate the expression pattern of Ephrin B2 in CD fibrosis and to explore its potential role in the modulation of autophagy and the AKT/mTOR signaling pathway, which were implicated in the fibrotic process. Methods The study used in vivo and in vitro methodologies to dissect the role of Ephrin B2 in intestinal fibrosis associated with Crohn’s disease. In vivo studies involved the generation of Ephrin B2 knockout mice and the induction of intestinal fibrosis using DSS-induced mice to assess the relationship between Ephrin B2 and intestinal fibrosis. In vitro studies utilized recombinant Ephrin B2 protein stimulation of CCD-18co cell lines to observe changes in autophagy-related proteins and the effects on fibroblast proliferation, activation, apoptosis, and collagen deposition. The study also investigated the impact of Ephrin B2 on signaling pathways such as PI3K/Akt/mTOR and RhoA/ROCK. Results Preliminary findings indicated that Ephrin B2 expression was significantly elevated in CD fibrosis patients and was associated with the modulation of intestinal autophagy genes. The in vivo model suggested a correlation between Ephrin B2 and the severity of intestinal fibrosis. In vitro studies showed that Ephrin B2 influenced the activation of fibroblasts and the deposition of collagen, potentially through the regulation of autophagy and the AKT/mTOR pathway. Conclusion This study provided evidence that Ephrin B2 might play a crucial role in CD-associated intestinal fibrosis. The findings suggested that targeting Ephrin B2 could be a novel therapeutic strategy for managing CD fibrosis. Further research is warranted to fully understand the mechanistic links between Ephrin B2, autophagy, and fibrosis in CD.

OP21 MIF-CD74 signaling promotes intestinal LTi-like ILC3s activation and gut fibrosis via upregulating pSTAT3

Abstract Background Intestinal fibrosis is a common complication of inflammatory bowel disease, and its core pathogenesis is fibroblast activation and massive extracellular matrix (ECM) deposition. In recent years, innate lymphoid cells (ILCs) have been shown to be an important source of fibroblast activation signals in fibrotic diseases. This study aims to explore the heterogeneity of ILC3 (the main ILC subgroup in the human intestine) in the intestinal fibrosis and the mechanism of its interaction with stromal cells. Methods The intestinal fibrosis model was constructed with ILC3 deficiency mice (Rorc knock out) treated with chronic DSS/TNBS. Flow cytometry was performed to detect the proportion of ILC3 subsets and cytokine expression level. ILC3 were sorted out for transcriptome sequencing and co-culture experiment with primary intestinal fibroblasts. Results In chronic DSS/TNBS models, the colon CCR6+ILC3 significantly expanded (p<0.05), and the expression of cytokine IL-22 was upregulated (p<0.05). ILC3 deficiency mice showed lower degree of intestinal fibrosis, including decrease in collagen involvement area (p<0.05) and decrease in ECM-related genes expression(p<0.05). After adoptively transferred of CCR6+ILC3, the severity of intestinal fibrosis in mice increases again. Flow cytometry revealed that CCR6+ILC3 was the main source of IL-22 in the mouse colon. CCR6+ILC3 cells were then sorted by flow cytometry, and co-cultured with mouse intestinal fibroblasts in vitro. Results shown that CCR6+ILC3 can activate fibroblasts. The expression level of α-SMA protein was significantly upregulated (p<0.05). Cell migration ability was also improved in the scratch experiment (p<0.05). Blocking IL-22 could inhibit the effects above. Transcriptome sequencing analysis of sorted ILC3 revealed a significant upregulation in signaling pathways related to cell activation, proliferation and adhesion, with CD74 existing in all of them. Flow cytometry confirmed the expression of CD74 on ILC3 for the first time, which specifically present on CCR6+ILC3 within RORγt+ cells. Cell stimulation experiments in vitro showed that macrophage migration inhibitory factor (MIF)-CD74 signal upregulated IL-22 level of ILC3 cells and was associated with increased phosphorylation of STAT3 signaling pathway. And MIF, the CD74 ligand, significantly increased in both mouse intestinal fibrosis models and stenosis tissue samples from CD patients (p<0.05). Conclusion CCR6+ILC3 is enriched in the intestinal fibrotic microenvironment and can continuously promote disease progression by activating fibroblasts through IL-22. CCR6+ILC3 can sense the pathogenic inflammatory factor MIF in chronic colitis through CD74, and increase IL-22 expression by promote STAT3 phosphorylation.

P0873 Risk factors for difficult endoscopic bowel dilatation of strictures among patients with inflammatory bowel disease (IBD): Findings from a IBD tertiary centers in Poland and Czech Republic

Abstract Background Intestinal strictures are a common and serious complication of inflammatory bowel disease (IBD). Endoscopic balloon dilatation (EBD) is the first step treatment to avoid the surgery. Methods The aim of this study was to assess the prevalence, risk factors and clinical sequelae of difficult EBD. In this retrospective, multi-center study, 861 IBD patients treated with EBD due to strictures were included. We evaluated the risk factors for difficult EBD, defined as a ≥3 per year. Results During 23.00 (14.00;42.00) months of median follow-up there were 392 (45.5%) easier EBD performed, while difficult EBD were done in 489 (54.5%) cases. Long term efficacy of EBD, defined as a >12 months without surgery was achieved in 392 (100%) easier vs in 457 (97.4%) difficult EBD, V = 0.11, P = 0.004. However, 149 (17.3%) patients underwent surgery due to unsuccessful EBD. The most important risk factors for difficult EBD, classified as modifiable, were smoking and treatment with adalimumab (especially if through level was normal) and ustekinumab. While vedolizumab (VDZ) and immunosuppressive therapy was identified as a protective factor. The multivariable logistic regression indicated good fit of the model to the data, pointing to protective role of total parental nutrition (TPN) and worsening of smoking (for both P < 0.001). Conclusion In this study, we observed a high incidence of difficult endoscopic balloon dilations present in 54.5% of cases. Treatment with adalimumab and ustekinumab, was a risk factor for more difficult endoscopic procedures, while the use of vedolizumab and total parental nutrition seems to have a protective effect. There has been an increasing number of difficult endoscopic procedures. Lower efficacy of these procedures leads to an increased frequency of complications, need for surgery, and the ever-increasing healthcare cost. Evaluating transmural healing during biological treatment using non-invasive techniques should therefore be identified as crucial factor. However, only prospective studies evaluating the effectiveness of such management in terms of accelerating the process of transmural healing and modifying the course of the disease in order to minimize the formation of strictures will ultimately guide new standards of care.

P0939 Efficacy of Ustekinumab-based integrated medicine therapy in patients with symptomatic stricturing Crohn’s disease: a retrospective study

Abstract Background Strictures are the most prevalent structural complication in Crohn’s disease (CD). Surgery and endoscopic balloon dilation are widely used worldwide. there is a lack of data regarding the use of ustekinumab (UST) for symptomatic stricturing CD in China. This study aims to assess the efficacy of UST in these patients and identify factors predicting treatment success. Methods This observational cohort study retrospectively included adult CD patients undergoing their first UST therapy for symptomatic strictures, confirmed via endoscopy or imaging. We defined the primary outcome as UST continuation without the prohibited treatments (corticosteroids, other biologics), endoscopic dilation, or bowel resection at week 52. Treatment effectiveness was evaluated according to the relief of symptoms, and baseline factors independently associated with success were identified using a logistic regression model. Results From June 2022 to April 2024, 73 patients were screened, of whom 54 were included in the study. Treatment success was observed in 44 out of 54 patients (81.5%) at week 52, while 10 patients required surgery or other biologics during follow-up. Regarding endoscopic stenosis remission, 11 (39%) patients could pass the colonoscope across the previously obstructed area, and the DBE-CD decreased from 3.85±0.15 to 3.04±0.24 (p=0.048). Complete resolution of prestenotic dilatations (<3.0 cm) on CT enterography was seen in 20 of 38 patients (53%). Intestinal ultrasound at 52 weeks showed an improvement (>25%) in bowel wall thickness in 23 (43%) of the 54 patients. UST reduced the International Bowel Ultrasound Segmental Activity Score (IBUS-SAS) from 71.71±5.23 to 54.73±5.41 (p=0.036). Faecal calprotectin levels normalized in 23 (43%) patients (p=0.01), while normalization of CRP was seen in 37 (69%) patients (p=0.25). Aside from one patient (2%) reporting leukemia and two patients (4%) reporting serious infections, no other severe adverse events were observed during the study. Conclusion Ustekinumab (UST) is effective in controlling the progression of intestinal strictures in Crohn’s disease (CD) patients. The majority of patients experienced symptom remission, improved stricture morphology, and a reduction in stricture-associated inflammation.

P1326 Fecal Microbiota Transplantation for Refractory and Recurrent Clostridium innocuum Infection in Inflammatory Bowel Disease: A Pilot Study on Safety, Clinical Outcomes, and Microbiota Changes

Abstract Background Clostridium innocuum has emerged as a pathobiome with vancomycin resistance, posing challenges in inflammatory bowel disease (IBD) management. In ulcerative colitis (UC) patients, C. innocuum is associated with reduced clinical remission rates, while in Crohn’s disease (CD) it correlates with creeping fat and intestinal stricture formation1,2. Some IBD patients experience refractory or recurrent C. innocuum infections, even after metronidazole treatment1. This study aimed to evaluate the safety and feasibility of fecal microbiota transplantation (FMT) for treating refractory or recurrent C. innocuum infections in IBD. Methods In this pilot study, seven IBD patients (3 CD, 4 UC) with refractory (n=5) or recurrent (n=2) C. innocuum infection post-metronidazole treatment were enrolled. Patients received FMT and were followed up for six months. Clinical efficacy was assessed using the Crohn’s Disease Activity Index and Mayo Score. Microbiota changes were analyzed through alpha diversity measures and Bray-Curtis dissimilarity metrics. Results No adverse events occurred in any of the seven participants. All participants demonstrated clinical improvement following FMT. However, a mild increase in symptom severity was observed at the six-month follow-up. Persistent C. innocuum infection was noted in one patient, with an asymptomatic recurrence in another three months post-FMT. Microbiome analysis showed increased alpha diversity post-FMT, and Bray-Curtis metrics (Figure 1) indicated donor-like microbiota composition. Conclusion FMT appears to be a safe and feasible option for IBD patients with refractory or recurrent C. innocuum infections. Further studies with larger cohorts are necessary to validate these findings and assess long-term efficacy.

P0447 Accurate, rapid and economical diagnosis of chronic enteropathy associated with SLCO2A1 gene and the analysis of its clinical pathological features

Abstract Background Chronic enteropathy associated with the SLCO2A1 gene (CEAS) is a rare intestinal disease caused by loss of protein function due to mutations in the SLCO2A1 gene. Currently, the clinical features of this disease are poorly understood, and diagnosis of lesions in the small intestine is challenging with limited methods, relying heavily on costly genetic sequencing. Therefore, this study aims to elucidate the clinical characteristics of Chinese CEAS patients and explore the diagnostic value of immunohistochemistry of biopsy tissues from duodenum, terminal ileum or colon site. Methods A retrospective analysis was conducted on 10 cases of CEAS admitted to the Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, from January 2015 to May 2024. Data including demographic information, clinical manifestations, laboratory and imaging results, pathological findings, genetic testing, and immunohistochemistry (IHC) results were analyzed. Results Of the 10 patients, 4 were male and 6 were female, the average age at onset was 25 years (IQR 17-36), and the average age at diagnosis was 41 years (IQR 39-44), with an interval of about 16 years from onset to diagnosis. Two patients had concurrent primary hypertrophic osteoarthropathy (PHO), both of whom were male. All patients had small intestine involvement, with the most common endoscopic findings being multiple strictures and superficial ulcers of the small intestine. Pathological findings indicated nonspecific chronic inflammation limited to the mucosa and submucosa. Five patients underwent surgical treatment, all involving partial small bowel resection. Genetic sequencing results indicated SLCO2A1 gene mutations in all 10 patients, with 7 patients having homozygous mutations and 3 having heterozygous mutations. Immunohistochemistry for SLCO2A1 protein on pathological specimens from the affected small intestine showed loss of SLCO2A1 expression in 9 patients and markedly reduced expression in 1 patient, with focal loss in specific vascular regions. Further immunohistochemistry of non-affected sites, including the descending duodenum and terminal ileum, also showed decreased or absent SLCO2A1 expression, consistent with findings in the affected areas. Conclusion CEAS is characterized by multiple small intestinal strictures, with a minority of patients also presenting with hypertrophic osteoarthropathy, which is more common in males. Immunosuppressants and biologics generally show poor efficacy. Historically, CEAS has been difficult to diagnose with a prolonged time to diagnosis, and genetic testing is costly and time-consuming. Immunohistochemical analysis of SLCO2A1 protein, regardless of whether the tissue is from affected or non-affected areas, can aid in early diagnosis.

P0902 Development and validation of a novel model based on clinical characteristic variables to predict disease behavior progression in patients with stricturing Crohn's disease

Abstract Background The risk factors for disease behavior progression in CD patients with strictures remain unclear. This study aims to construct a predictive model based on commonly used clinical indicators to identify high-risk CD patients with early progression. Methods We conducted a retrospective analysis of clinical data from stricturing Crohn’s disease patients at The First Affiliated Hospital of Sun Yat-sen University from October 2016 to October 2023. The disease behavioural progression was defined as progression to B3 classification or under surgery due to intestinal strictures. The data were split into a test set and an internal validation set in a 7:3 ratio. Classification models, including logistic regression (LR), random forest (RF) and extreme-gradient Boosting (XGB) Models, were constructed. Finally, all models were validated in an independent external validation cohort from Ruijin Hospital, Shanghai Jiaotong University School of Medicine.[Figure 1] Results The study included 341 patients, with 190 in the internal training set, 81 in the test set, and 70 in the external validation set. Obstructive symptoms, globulin (GLB), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) are independent predictors of disease behavior progression. The areas under the receiver-operating characteristic curves (AUROCs) of the LR, RF, and XGB models were 0.861, 0.477 and 0.559, respectively. The logistic regression model achieved the highest AUROC value of 0.752 in the external validation. The further transformed nomogram has a similar prediction accuracy to the logistic regression. Conclusion In patients with stricturing CD, obstructive symptoms score, CRP, ESR and GLB were independent and validated predictors of disease behavior progression in stricturing Crohn's disease. We found no evidence of better performance of machine learning-based models in predicting disease behavior progression in stricturing CD. A nomogram based on the logistic regression model might aid in the management of stricturing CD patients.

P1194 Evaluating the Cost-Utility of Intestinal Resection Before Anti-Tumor Necrosis Factor Therapy for Strictures in Crohn's Disease in China

Abstract Background Crohn's disease is a chronic, relapsing immune-mediated disorder. Stricturing Crohn's disease is severe and frequent complication. The therapeutic landscape has been revolutionized with the advent of biologic agents. Methods A hybrid model was used. The model consisted of a decision tree model component and a Markov model component with 10-year follow-up for assessing the different therapies. Quality-adjusted life-years and costs were discounted at an annual rate of 5%. A sensitivity analysis was performed to evaluate the resilience of the results in the face of parameter uncertainty. Results According to our base-case analysis results, maintenance treatment with adalimumab after enterectomy is the most cost-effective (more quality-adjusted life-years gained and less cost incurred), followed by adalimumab ($47,709.37/QALY vs. $45,986.53/QALY vs. $66,526.40/QALY vs. $46,186.51/QALY). The results of one-way sensitivity analysis and probabilistic sensitivity analysis demonstrated the robustness of the model and base-case analysis accounting for the uncertainty of parameters. Conclusion In patients treated surgically after an initial diagnosis of intestinal stricture, adalimumab is a biologic agent that should be recommended for later maintenance therapy. In contrast, surgery may be recommended later in patients who were not treated surgically at the outset. References Knowles, S., et al., Quality of Life in Inflammatory Bowel Disease: A Systematic Review and Meta-analyses-Part II. Inflammatory bowel diseases, 2018. 24(5): p. 966-976. Rieder, F., C. Fiocchi, and G. Rogler, Mechanisms, Management, and Treatment of Fibrosis in Patients With Inflammatory Bowel Diseases. Elsevier, 2017(2). Mak, J.W.Y. and S.C. Ng, Epidemiology of fibrostenosing inflammatory bowel disease. Journal of digestive diseases, 2020. 21(6): p. 332-335. Lin SN, M.R., Qian C, Bettenworth D, Wang J, Li J, Bruining DH, Jairath V, Feagan BG, Chen MH, Stenosis Therapy and Antifibrotic Research (STAR) Consortium; Rieder F. Development of antifibrotic therapy for stricturing Crohn's disease: lessons from randomized trials in other fibrotic diseases. Physiol Rev, 2022.

DOP117 Innate lymphoid cells control colitis and intestinal fibrosis via cellular stress response in mice and human

Abstract Background Group 2 innate lymphoid cells (ILC2s) are increased in peripheral blood and intestinal samples from IBD patients and mice with colitis. ILC2s are major producers of type 2 cytokines including IL-5 and IL-13 and growth factor AREG that induce goblet cell hyperplasia and mitigate acute inflammation in the gut. On the other hand, prolonged or uncontrolled ILC2 activation may contribute to chronic inflammation and tissue fibrosis, although the role of ILC2s in stricturing/fibrostenotic Crohn’s disease (CD) has been unknown. In this study, we investigated the function of IRE1a-XBP1 pathway, a regulatory hub of cellular stress response, in colitis and fibrosis in mice and CD patients. Methods We generated conditional knockout Ire1aflo/floxIl5-Cre (Ire1aΔIl5) and Rag-/-Ire1aΔIl5 mice with Ire1a deleted in ILC2s. Dextran sodium sulfate (DSS)-induced and T-cell transfer colitis models were used. Human peripheral ILC2s were collected for flow cytometry and ex vivo stimulations. Results Mouse intestinal ILC2s express high level of Ire1a. The number of ILC2s increased in colon, small intestine (SI), and esophagus of Ire1aΔIl5 mice with elevated proliferation marker Ki67. Additionally, SI and colonic Ire1aΔIl5 ILC2s produced more IL-5, IL-13, and AREG after ex vivo stimulation with IL-33 or IL-25. Consistently, selective IRE1 inhibitor 4u8C enhanced production of IL-13, while selective IRE1 activator IXA4 suppressed IL-13 in sort-purified human ILC2s ex vivo (Figure 1). Bulk RNA-seq of SI Ire1aΔIl5 ILC2s showed reduced Rxrg and elevated fatty acid transport by pathway analysis, which may lead to the increased proliferation and cytokine production in Ire1aΔIl5 ILC2s. Upon DSS challenge, Ire1aΔIl5 mice exhibited milder signs of disease including weight loss, clinical scores as well as colon shortening and histology, which was accompanied by elevations in ILC2-derived cytokines and AREG as well as heightened goblet cell differentiation and mucin production. In contrast, upon adoptive T-cell transfer, Rag-/-Ire1aΔIl5 mice developed worsened chronic colitis and intestinal fibrosis, which was reversed by intraperitoneal injection of neutralizing antibody against IL-13 or AREG. Furthermore, CD patients with intestinal strictures expressed higher level of IL-13 in ILC2s in the blood (Figure 2). Conclusion IRE1a-XBP1 constrains cytokine production by intestinal ILC2s during inflammation. IRE1a deficiency in ILC2s protected against acute colitis with heightened type 2 cytokines and AREG; while loss of IRE1a exacerbated chronic colitis and fibrosis. The presence of CD strictures was associated with elevated IL-13 in peripheral ILC2s . We identified IRE1a and ILC2s as potential biomarkers and therapeutic targets for stricturing CD.

P0750 Association between intestinal fibrosis and clinical and surgical recurrence after intestinal resection in stenotic Crohn's disease patients

Abstract Background Despite recent advances in the medical care of Crohn's disease (CD), most patients, particularly those with stenosis, still require intestinal resection during their disease course. However, more than half of the patients experience postoperative recurrence. Intestinal fibrosis is an important pathological feature of stenotic Crohn's disease. We aim to investigate the association between fibrosis at the site of intestinal stenosis and normal area and risk of clinical and surgical recurrence after first intestinal resection in patients with stenotic Crohn's disease. Methods A retrospective, multi-center study was conducted on stenotic Crohn's disease patients who received first intestinal resection between January 2010 and July 2023. The most representative pathological slides from the resected stenotic intestinal tissues and normal slides from the normal tissues were selected. We used Masson's trichrome staining to visualize collagen fibers and calculated the proportion of collagen fiber area in the slides using the Image-Pro-Plus software to assess the degree of intestinal fibrosis. Baseline information and postoperative clinical recurrence were collected through electronic medical record systems and telephone follow-up. Survival analysis and univariate and multivariate Cox regression models were used to assess the impact of intestinal fibrosis on clinical and surgical recurrence. Results 257 patients were included in this study. 94 (36.5%) and 25 (9.7%) of the patients experienced clinical and surgical recurrence during the follow-up period, respectively. In the univariate cox analysis, high degree transmural intestinal fibrosis at stenotic area was significantly associated with clinical recurrence (HR 4.94, 95%CI 2.72-8.96, P<0.001) and surgical recurrence (HR 4.45, 95%CI 1.45-13.72, P=0.009). This association remained significant when considering fibrosis only in the mucosa, submucosa, muscular layers of stenotic area, or in the normal area. In the multivariate cox analysis, transmural fibrosis was still related to clinical recurrence. Conclusion The degree of transmural fibrosis at the site of intestinal stenosis and normal area was significantly associated with clinical recurrence after first intestinal resection in patients with stenotic Crohn's disease. Intestinal fibrosis should be considered in postoperative treatment and follow-up decision-making.

P1282 Type 2 diabetes mellitus in IBD patients: a case control study through a long follow up period

Abstract Background The characterization of patients with Inflammatory Bowel disease (IBD) and Type 2 Diabetes Mellitus (T2DM), as a new category, has not been detailed yet. The main endpoint was evaluating how diabetes may affect IBD course. Additionally, we analysed the prevalence of liver steatosis and liver damage in these patients. Methods We conducted a retrospective case-control study, comparing the occurrence of a severe IBD in patients with IBD+T2DM (cases) versus patients with IBD alone (controls). Among 1047 medical records, we selected all the patients with IBD-T2DM, randomly choosing controls in a 1:4 ratio. We defined severe IBD as the occurrence of at least one of the following factors: IBD-related surgery; initiation of target therapy; over two courses of systemic corticosteroids in a year; IBD-related hospitalization; diarrhoea for more than 12 months with nocturnal awakenings/urgency; symptomatic intestinal stenosis. We defined liver damage as a Fib-4 value > 1.3; hepatic steatosis was assessed via instrumental exams. Results We included 79 IBD-T2DM patients comparing them with 308 patients with IBD alone. The presence of a severe disease was similar in the two groups (59.5% vs 59.7%; p=0.97). Statistically significant differences emerged about the presence of hepatic steatosis (62.9%vs 27.2%; p<0.0001) and liver damage (55.4% vs 26.6%; p<0.0001). In univariate analysis, hypertension (HR: 1.61; p = 0.047), dyslipidaemia (HR: 1.68. p = 0.03) and being naïve to thiopurines (HR: 1.81 p = 0.02) contribute to increase liver damage risk, though these variables were not significant in multivariate analysis. In the IBD-T2DM group, we found a higher current (2.6% vs 1.4%) and past (64.9% vs 34.7%; p<0.0001) use of systemic corticosteroids and a lower current (7.6% vs 12.8%) and past (7.6% vs 20.2%) use of anti-TNF-alpha drugs (p=0.007). Median age at diagnosis of IBD was higher in cases (48.0 vs 32.0; p < 0.0001). In a sub-analysis of Crohn’s disease (CD), 24.3% of the CD-T2DM group had an exclusively colonic involvement vs 5% in the group without T2DM (p=0.003). Conclusion In our study, T2DM was not associated with an IBD worse clinical course. Secondly, we observed an increased presence of steatosis and liver injury, but the IBD-T2DM combination was not a multiplicative risk factor for these outcomes. In clinical practice, we observed a larger use of systemic corticosteroids and a lower use of anti-TNF-alpha drugs in IBD-T2DM patients. Differences such as age of disease onset, colonic involvement, and liver damage, suggest that IBD-T2DM patients could configure a special population worthy of further studies. References Yarur AJ, Strobel SG, Deshpande AR, Abreu MT. Predictors of aggressive inflammatory bowel disease. Gastroenterol Hepatol (NY). 2011;7(10):652-659. CDC. National Diabetes Statistics Report. Diabetes. Published June 6, 2024. Accessed June 12, 2024.https://www.cdc.gov/diabetes/php/data-research/index.html Gomollón F, Dignass A, Annese V, et al. 3rd European Evidence-based Consensus on the Diagnosis and Management of Crohn’s Disease 2016: Part 1: Diagnosis and Medical Management. Journal of Crohn’s and Colitis. 2017;11(1):3-25. doi:10.1093/ecco-jcc/jjw168

Flexible Vacuum-assisted Ureteral Access Sheath for Treating Impacted Ureteral Stones.

To evaluate the feasibility and safety of using the novel flexible vacuum-assisted ureteral access sheath (FV-UAS) in flexible ureteroscopy (F-URS) treatment of impacted non-distal ureteral stones. We analyzed data from patients who underwent FV-UAS treatment for impacted non-distal ureteral stones between January 2022 and September 2023. Perioperative parameters were evaluated, including operative time, ureteral injury, and complications. The FV-UAS have a 10 cm passive deflection segment at the distal end of the ureteral access sheath that can bend following the deflection of the F-URS, while also being connected to a vacuum device for aspiration. A total of 62 consecutive patients (35 females) were included. Mean (range) patient age was 50.0 (29-75) years. Mean (range) largest stone size was 13.8 (9-16) mm. Mean (range) total time was 34.2 (18-46) min. In 57 patients (91.9%), no residual stones were detected in the renal, while 5 patients (8.1%) had residual stones smaller than 4 mm. A 5-tier classification quantified ureteral injury severity at stone impaction sites: grade 0 (n=10); grade 1 (n=47); grade 2 (n=5); grade 3 and 4 (n=0). Nine patients (14.5%) underwent placement of two double-J stent. Two patients (3.2%) developed postoperative fever requiring antibiotics and conservative management. Mean (range) postoperative hospital stay was 1.2 (1-2) day. At the 3-month follow-up, no ureteral strictures had occurred. No additional surgical interventions were necessary during follow-up. The use of the FV-UAS for the treatment of impacted non-distal ureteral stones is a safe and effective surgical method.

Endoscopic radial incision and cutting using balloonassisted enteroscopy for small intestinal stenosis related to Crohn's disease: a pilot study.

Radial incision and cutting (RIC) is an alternative dilation method for stenosis of the lower gastrointestinal tract. However, its safety and efficacy for the small intestine requiring balloon-assisted enteroscopy (BAE) remain limited. Therefore, this pilot study aimed to evaluate the safety and efficacy of RIC using BAE. We included 10 patients with Crohn's disease and performed 12 sessions of RIC for 10 lesions. The rate of adverse events 1 month after RIC was the primary outcome, whereas short- and long-term prognoses and improvements in subjective symptoms that were evaluated using a visual analog scale were the secondary outcomes. The technical success rate for RIC, defined as scope passage immediately following the procedure, was 100% (12/12). The rates of delayed bleeding and perforation were 0% (0/12). One patient developed restenosis because of the worsening of Crohn's disease and underwent surgery 2 months after RIC. The cumulative restenosis-, reintervention-, and surgery-free rates at 1 year after RIC were 67.5%, 78.7%, and 90.0%, respectively. Abdominal pain, abdominal bloating, nausea, and difficulties in defecation significantly improved 4 weeks after RIC. RIC for small intestine using BAE has the potential to be safe and effective for relieving symptoms (jRCT identifier jRCTs022200040).