Perianal Fistulizing Crohn's Disease Research Articles

Prevalence and risk factors of depression among patients with perianal fistulizing Crohn's disease.

Psychological distress, especially depression, associated with perianal fistulizing Crohn's disease (PFCD) is widespread and refractory. However, there is a surprising paucity of studies to date that have sought to identify the prevalence and risk factors of depression associated with PFCD. To estimate the prevalence of depressive symptoms and investigate the depression-related risk factors in patients with PFCD. The study was conducted in the form of survey and clinical data collection via questionnaire and specialized medical staff. Depressive symptoms, life quality, and fatigue severity of patients with PFCD were assessed by Patient Health Questionnaire-9, Inflammatory Bowel Disease Patient Quality of Life Questionnaire (IBDQ), and Inflammatory Bowel Disease (IBD) Fatigue Patient Self-assessment Scale. The basic demographic information, overall disease features, perianal clinical information, and laboratory inflammation indicators were also gathered. Multivariate regression analysis was ultimately used to ascertain the risk factors of depression associated with PFCD. A total of 123 patients with PFCD were involved, and 56.91% were suffering from depression. According to multivariate logistic regression analysis, Perianal Disease Activity Index (PDAI) score [odds ratio (OR) = 0.69, 95% confidence interval (CI): 0.50 to 0.95], IBDQ score (OR = 0.93, 95%CI: 0.88 to 0.97), modified Van Assche index (OR = 1.24, 95%CI: 1.01 to 1.53), and IBD Fatigue score (OR = 1.72, 95%CI: 1.23 to 2.42) were independent risk factors of depression-related prevalence among patients with PFCD (P < 0.05). Multiple linear regression analysis revealed that the increasing perianal modified Van Assche index (β value = 0.166, 95%CI: 0.02 to 0.31) and decreasing IBDQ score (β value = -0.116, 95%CI: -0.14 to -0.09) were independently associated with the severity of depression (P < 0.05). Depressive symptoms in PFCD patients have significantly high prevalence. PDAI score, modified Van Assche index, quality of life, and fatigue severity were the main independent risk factors.

Perianal Fistulizing Crohn's Disease: Outcomes of Surgical Repairs and Current State of Stem Cell-Based Therapies

AbstractPerianal fistulizing Crohn's disease is one of the most disabling phenotypes of Crohn's disease, due to the severe impairment in quality of life including social and personal wellbeing. A multimodal approach with patient-tailored care is the key to optimal management of this condition. Medical therapy is needed to optimize the luminal disease, and surgical intervention is required to control any associated perianal sepsis and attempt palliative or definitive fistula repair. While several medical and surgical options are available, the majority of patients continue to have symptomatic disease. Fortunately, this continues to drive novel innovations which are revolutionizing the treatment and outcomes of perianal fistulizing Crohn's disease. However, there continues to be a need for randomized trials and consistent metrics utilized for classification and treatment outcomes in order to accurately describe optimal treatment outcomes.

A phase I/II clinical trial of ex-vivo expanded human bone marrow derived allogeneic mesenchymal stromal cells in adult patients with perianal fistulizing Crohn’s Disease

BackgroundPerianal fistulas (PF) affect one-third patients with Crohn’s disease (CD) with limited therapeutic options. There is dearth of literature on safety and efficacy of bone marrow-derived mesenchymal stromal cells (BMSCs) in this population.MethodsAn open-label, phase I/II, single-arm study was conducted involving local administration of human allogeneic bone marrow-derived mesenchymal stromal cells in perianal fistula of patients with Crohn’s disease refractory to standard therapies. Clinical severity and biomarkers were assessed at baseline and periodically until week 104 , and MRI at week 24 and 104. Primary and secondary objectives were to assess safety and efficacy respectively. Fistula remission was complete closure of fistula openings with < 2 cm perianal collection on MRI, and fistula response was decrease in drainage by ≥ 50%. Change in perianal disease activity index, quality-of-life and Van Assche index on MRI over time was assessed using mixed-effect linear regression model.ResultsTen patients (male:8, mean age:27.4 ± 12.0years) were recruited. Self-resolving procedure-related adverse events occurred in three patients, with no follow-up adverse events. In intention to treat analysis at week 24, two patients (20%) achieved fistula remission and seven (70%) had fistula response. At week 52, two (20%) patients were in remission and seven (70%) maintained response. At 104 weeks, two (20%) patients maintained response and one (10%) was in remission. Statistically significant decrease in perianal disease activity index (P = 0.008), Van Assche Index (P = 0.008) and improvement in quality-of-life (P = 0.001) were observed over time.ConclusionsAllogeneic BMSCs are safe and effective for the treatment of perianal fistulizing CD with significant improvement in clinical severity and radiological healing.Trial registrationThe study was prospectively registered on Clinical trials registry – India (CTRI), CTRI/2020/01/022743 on 14 January 2020, http://ctri.nic.in.

Ten missteps in the management of inflammatory bowel disease in Asia: An expert report by the Asian Pacific Association of Gastroenterology Working Group on Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD) is rapidly emerging in the Asia Pacific region. However, there are many challenges in the diagnosis and management of this condition. The Asian Pacific Association of Gastroenterology (APAGE) Working Group on IBD conducted a round table meeting to identify 10 common mistakes in the management of IBD in Asia. To summarize, many physicians still over rely on a definitive histological diagnosis before starting treatment and do not fully establish disease extent such as perianal and proximal gastrointestinal involvement in Crohn's disease (CD) or extent of involvement in ulcerative colitis (UC). It is also essential to actively look for evidence of extra-intestinal manifestations, which may influence choice of therapy. In terms of conventional therapy, underuse of topical 5 aminosalicylates (5-ASAs) in UC and inappropriate dosing of corticosteroids are also important considerations. Acute severe UC remains a life-threatening condition and delay in starting rescue therapy after inadequate response to intravenous steroids is still common. Anti-tumor necrosis factors should be considered first line in all cases of complex perianal fistulizing CD. Most patients with IBD are on potent immunosuppressive therapy and should be screened for latent infections and offered vaccinations according to guidelines. Under-recognition and management of significant complications such as anemia, osteoporosis, malnutrition, and thromboembolism should also be addressed. Colonoscopy is still not properly performed for dysplasia/cancer surveillance and for evaluating post-op recurrence of CD. Another common misstep is inappropriate withdrawal of medications during pregnancy leading to increased complications for the mother and the newborn.

TOpCLASS Expert Consensus Classification of Perianal Fistulizing Crohn's Disease: A Real-World Application in a Serial Fistula MRI Cohort.

Perianal fistulizing Crohn's disease (PFCD) is an aggressive phenotype of Crohn's disease defined by frequent relapses and disabling symptoms. A novel consensus classification system was recently outlined by the TOpCLASS consortium that seeks to unify disease severity with patient-centered goals but has not yet been validated. We aimed to apply this to a real-world cohort and identify factors that predict transition between classes over time. We identified all patients with PFCD and at least one baseline and one follow-up pelvic (pMRI). TOpCLASS classification, disease characteristics, and imaging indices were collected retrospectively at time periods corresponding with respective MRIs. We identified 100 patients with PFCD of which 96 were assigned TOpCLASS Classes 1 - 2c at baseline. Most patients (78.1%) started in Class 2b, but changes in classification were observed in 52.1% of all patients. Male sex (72.0%, 46.6%, 40.0%, p = 0.03) and prior perianal surgery (52.0% vs 44.6% vs 40.0%, p = 0.02) were more frequently observed in those with improved class. Baseline pMRI indices were not associated with changes in classification, however, greater improvements in mVAI, MODIFI-CD, and PEMPAC were seen among those who improved. Linear mixed effect modeling identified only male sex (-0.31, 95% CI -0.60 to -0.02) with improvement in class. The TOpCLASS classification highlights the dynamic nature of PFCD over time, however, our ability to predict transitions between classes remains limited and requires prospective assessment. Improvement in MRI index scores over time was associated with a transition to lower TOpCLASS classification.

Does combined medical and surgical treatment improve perianal fistula outcomes in patients with Crohn's disease? A systematic review and meta-analysis.

The optimal treatment of perianal fistulizing Crohn's disease (PFCD) is unknown. We performed a systematic review with meta-analysis to compare combined surgical intervention and anti-TNF therapy (combined therapy) vs. either therapy alone. MEDLINE, EMBASE, and Cochrane databases were searched systematically through December 2023. Surgical intervention was defined as an exam under anesthesia ± setons. We calculated weighted risk ratios (RR) with 95% confidence intervals (CI) for our co-primary outcomes: fistula response and healing, defined clinically as a reduction in fistula drainage or number of draining fistulas and fistula closure respectively. Thirteen studies were analysed: 515 patients treated with combined therapy, 330 patients with surgical intervention and 406 patients with anti-TNF therapy with follow-up between 10 weeks and 3 years. Fistula response (RR 1.10; 95% CI, 0.93-1.30, p=0.28) and healing (RR 1.06; 95% CI, 0.86-1.31, p=0.58) was not significantly different when comparing combined therapy with anti-TNF therapy alone. In contrast, combined therapy was associated with significantly higher rates of fistula response (1.25; 95% CI, 1.10-1.41, p<0.001) and healing (RR 1.17; 95% CI, 1.00-1.36, p=0.05) compared with surgical intervention alone. Our results remained stable when limiting to studies that assessed outcomes within 1 year and studies where <10% of patients underwent fistula closure procedures. Combined surgery and anti-TNF therapy was not associated with improved PFCD outcomes compared with anti-TNF therapy alone. Due to an inability to control for confounding and small study sizes, future, controlled trials are warranted to confirm these findings.

Efficacy and Safety of Filgotinib for the Treatment of Perianal Fistulizing Crohn's Disease [DIVERGENCE 2]: a Phase 2, Randomized, Placebo-Controlled Trial.

There is an unmet need for the treatment of perianal fistulizing Crohn's disease [PFCD]. This study evaluated the efficacy and safety of the Janus kinase 1 preferential inhibitor filgotinib, for the treatment of PFCD. This phase 2, double-blind, multicentre trial enrolled adults with PFCD and prior treatment failure. Participants were randomized [2:2:1] to receive filgotinib 200mg, filgotinib 100mg, or placebo once-daily orally for up to 24 weeks. The primary endpoint was combined fistula response [reduction from baseline of at least one draining external opening determined by physical assessment, and no fluid collections >1cm on pelvic magnetic resonance imaging (MRI)] at week 24. Between April 2017 and July 2020, 106 individuals were screened and 57 were randomized. Discontinuations were lowest in the filgotinib 200mg group [3/17 (17.6%) versus 13/25 (52.0%) for filgotinib 100mg and 9/15 (60.0%) for placebo]. The proportion of participants who achieved a combined fistula response at week 24 was 47.1% [8/17; 90% confidence interval (CI) 26.0, 68.9%] in the filgotinib 200mg group, 29.2% [7/24; 90% CI 14.6, 47.9%] in the filgotinib 100mg group, and 25.0% [3/12; 90% CI 7.2, 52.7%] in the placebo group. Serious adverse events occurred more frequently with filgotinib 200mg [5/17 (29.4%)] than with placebo [1/15 (6.7%)]. There were no treatment-related serious adverse events or deaths. Filgotinib 200mg was associated with numerical reductions in the number of draining perianal fistulas based on combined clinical and MRI findings compared with placebo, and was generally well tolerated. [NCT03077412].

P707 Real-world Long-term efficacy of ustekinumab in the treatment of Perianal Fistulizing Crohn's disease: Results from a single-center retrospective study

Abstract Background The efficacy of ustekinumab (UST) in treating perianal fistulizing Crohn's disease (PFCD) remains inconclusive. This study aimed to investigate the long-term efficacy and prognostic factors of UST in the treatment of PFCD patients. Methods This is a retrospective single-center analysis of PFCD patients who had at least one year of follow-up and began UST treatment between November 2020 and September 2022. The primary outcome was fistula clinical remission at any time point. Secondary outcomes included fistula clinical response, intestinal clinical remission, and response. Factors associated with long-term fistula clinica remission were screened using the univariate analysis, LASSO regression and extreme gradient boosting (XGBoost) model, and visualized using SHAP. Results A total of 131 patients were included in the study, the mean follow-up was 70.39 weeks. Among these patients, 51 (38.9%), 72 (55.0%), and 82 (62.6%) achieved clinical fistula remission at weeks 24, 52, and the last follow-up, respectively. 111 patients (84.7%) achieved intestinal clinical remission and 119 patients (90.8%) achieved intestinal clinical response. Ninety-one patients (69.5%) had prior exposure to other biologics. This study did not ascertain a significant difference in the outcome of UST for CD between biologics Naïve and biologics Exposure patients. The XGBoost model integrated eight independent variables: Montreal L3, Montreal A2, CDAI, PDAI, ESR, body mass index, simple fistula, and re-operation events. The model revealed a favourable discrimination ability with AUC was 0.798 in the internal cohorts. Conclusion This study defined the effectiveness and eight risk factors of UST in long-term clinical fistula remission in PFCD patients, which is helpful for early identification of UST beneficiaries.

OP31 Single-cell analyses identify immune and stromal signatures of perianal fistulizing Crohn's Disease

Abstract Background Perianal fistulas occur in ~30-40% of Crohn’s disease (CD) patients associated with high morbidity and an impaired quality of life. The management of perianal fistulizing CD is a major clinical challenge, where its underlying etiology remains poorly understood. Methods We recruited patients with 1) CD with perianal fistulas (PCD; n = 12); 2) CD without perianal involvement (NPCD; n = 10); 3) idiopathic perianal fistulas (IPF; n = 21). Biopsies were taken from the fistula tracts, external opening of the fistulas, and rectal mucosa during examination under anesthesia or colonoscopy. Mucosal immune cells were analyzed using mass cytometry (or CyTOF), while all cells from PCD and IPF fistula tracts (n = 5 or 6) were characterized using single-cell RNA-sequencing. Results CyTOF revealed a skewed mucosal immune landscape in PCD. E.g., PCD fistula tracts harbored elevated CD45RO+ T cells including Tregs with increased expression of TIGIT and CD226 compared to IPF. PCD also expanded Th17 cells in the fistula tracts and IL-17-producing CD8 T cells (Tc17) in the rectum. Altered exhaustion markers CD39 and CD127 were present in both CD4 and CD8 T cells from PCD fistula tracts, external fistula openings, and rectum compared to IPF and NPCD. Regulatory B cells (Bregs), with immunomodulatory function in the gut, were dramatically diminished in PCD compared to IPF. In addition, PCD fistula tracts, fistula opening, and rectum all exhibited substantially higher CD172+TREM1+ macrophages, which were previously found to promote luminal CD (Figure 1; only fistula tract data are shown). Using scRNA-seq, we unraveled immune and stromal cell compartments in PCD and IPF fistula tracts (Figure 2). We also identified a small mast cell population, which was diminished in PCD. Mast cells are involved in tissue repair and remodeling in other diseases, although their presence in perianal fistulas was previously unknown. Three fibroblast populations (cluster 4, 6, 7 in figure 2D), with elevated activities in interferon signaling, IL-6-JAK-STAT3 pathway, TNF signaling, as well as TGF-B and epithelial-mesenchymal transition, were dramatically increased in PCD compared to IPF. Ongoing studies are focusing on spatial transcriptomics and functional analysis of fistula-associated immune cells and fibroblasts. Conclusion Using single cell analysis of the fistula tracts and nearby tissues from an extensive patient population, we revealed previously unknown immune and stromal cell landscapes of PCD. Our findings highlight the pathogenic roles of IL-17 signaling, T cell exhaustion, pathogenic macrophages, and pro-inflammatory/remodeling fibroblasts in the pathogenesis of PCD. This study may open new avenues for disease-specific therapies for this challenging condition.

Scoring indices for perianal fistulizing Crohn's disease: A systematic review.

In this systematic review we summarize existing scoring indices for assessing disease activity and quality of life in perianal fistulizing Crohn's disease (PFCD) and highlight gaps in the literature. MEDLINE, EMBASE, and CENTRAL were searched from 24 August 2022 to identify studies evaluating clinical, radiological, or patient-reported outcome measures (PROMS) in PFCD. The primary objective was to identify all available scoring indices and describe the operating properties of these indices. Fifty-three studies reported on the use of one clinical index (Perianal Disease Activity Index: PDAI), three PROMs and ten radiological indices. Twenty-five studies evaluated the operating properties of these indices. The PDAI demonstrated content validity, construct validity and responsiveness but criterion validity or reliability were not assessed. The Van Assche index (VAI), modified VAI and the Magnetic Resonance Index for Assessing Fistulas in Patients with CD (MAGNIFI-CD) were the most studied radiological indices. These indices demonstrated responsiveness and reliability. The VAI and MAGNIFI-CD demonstrated construct validity. Criterion and content validity and feasibility have not been assessed. Among the three PROMs, the Crohn's Anal Fistula Quality of Life index demonstrated content and construct validity, inter-observer reliability and responsiveness. Criterion validity, intra-observer reliability and feasibility have not been assessed for this index. There are no fully valid, reliable, and responsive clinical disease or radiological indices for PFCD. Although the radiological indices demonstrated responsiveness and reliability, well-defined cut-offs for response and remission are lacking. Future research should focus on establishing standardized definitions and thresholds for outcomes.

Endoscopic Setons Placement for Complex Perianal Fistulizing Crohn's Disease by Fistuloscopy Using Ultra-thin Endoscope Introduced into Fistula Cavity

Endoscopic Setons Placement for Complex Perianal Fistulizing Crohn's Disease by Fistuloscopy Using Ultra-thin Endoscope Introduced into Fistula Cavity

Analysis on the efficacy of dual vein induction therapy of Ustekinumab in complex perianal fistulizing Crohn's disease

Objectives: To analyze the efficacy of dual vein induction therapy of Ustekinumab (UST) in complex perianal fistulizing Crohn's disease (PFCD). Methods: Clinical data of patients diagnosed with complex PFCD in the Second Affiliated Hospital of Wenzhou Medical University from January 2022 to March 2023 were retrospectively analyzed. After sufficient single intravenous infusion of UST (6 mg/kg) at week 0 and 8, every patient received single subcutaneous injection of UST 90 mg every 8 weeks for maintenance treatment. At week 8, 16, and 22-26, clinical outcomes of anal fistula were evaluated using perianal disease activity index (PDAI), and overall activity of the patients was evaluated using Harvey Bradshaw index (HBI). At week 22-26, Van Assche Index (VAI) was used to evaluate imaging outcome of anal fistula, and simplified endoscopic score of Crohn's disease (SES-CD) was employed to assess intestinal outcome events. The above indexes were compared in the patients before and after UST treatment. PFCD patients were divided into first-line UST treatment group and non first-line UST treatment group according to whether first-line UST treatment was used, the differences in anal fistula response rate and remission rate, intestinal response rate and remission rate as well as overall activity response rate and remission rate were compared between the two groups. Results: A total of 60 PFCD patients were included, including 46 males and 14 females, aged [M (Q1, Q3)] 25.0 (20.8, 30.0) years old. The clinical response rates of anal fistula [41.7% (25/60), 55.0% (33/60) and 63.3% (38/60), respectively, P=0.056] and the clinical remission rates of anal fistula [21.7% (13/60), 31.7% (19/60) and 43.3% (26/60), respectively, P=0.002] gradually increased at week 8, 16, 22-26. The overall activity response rates [53.3% (32/60), 70.0% (42/60), 83.3% (50/60), respectively, P=0.040] and the overall activity response rates [41.7% (25/60), 61.7% (37/60), 75.0% (45/60), respectively, P=0.001] also gradually increased at week 8, 16, 22-26. At week 22-26, the partial response rate and fistula healing rate of anal fistula imaging were 45.0% (27/60) and 38.3% (23/60), respectively. The endoscopic response rate and endoscopic response rate were 73.7% (44/60) and 45.0% (27/60), respectively. The endoscopic response rate of patients receiving first-line UST treatment [23 males and 8 females, aged 22.0 (21.0, 39.0) years] was higher than that of patients receiving non first-line UST treatment[23 males and 6 females, aged 26.5 (20.0, 30.0) years,87.1% vs 58.6%, P=0.013]. Conclusion: The dual vein induction therapy of UST could effectively improve the clinical efficacy in patients with complex PFCD.

Persistent Inflammation of the Rectum in Perianal Fistulizing Crohn's Disease Is Associated With Goblet Cell Function

Persistent Inflammation of the Rectum in Perianal Fistulizing Crohn's Disease Is Associated With Goblet Cell Function

Management of Perianal Fistulizing Crohn's Disease.

Perianal fistulizing Crohn's disease (CD) represents a severe phenotype of CD that is associated with significant morbidity and reduction in quality of life. Perianal fistulizing CD is caused by a complex interplay of genetic predisposition, immune dysregulation, gut dysbiosis, and various unknown physiological and mechanical factors. A multidisciplinary approach is hence required for optimal management . A detailed anatomical description and classification of perianal fistula, including comprehensive clinical, endoscopic, and radiological diagnostic workup, is an important prerequisite to treatment. For simple perianal fistulas, use of antibiotics and immunomodulators, with or without fistulotomy, are appropriate measures. The medical management of complex perianal fistula, on the other hand, requires adequate control of infection before initiation of therapy with immunomodulators. In active complex perianal fistula, anti-tumor necrosis factors remain the most accepted therapy, with concomitant use of antibiotics or immunomodulators enhancing the efficacy. For patients refractory to anti-tumor necrosis factors, treatment with anti-integrins, anti-interleukins, and small molecules is being evaluated. Mesenchymal stem cells, hyperbaric oxygen therapy, and exclusive enteral nutrition have also been investigated as adjunct therapies. Despite the expansion of the medical armamentarium, a large proportion of the patients require surgical interventions. In this review, we provide an up-to-date overview of the pathophysiology, clinical presentation, diagnosis, and medical management of perianal fistulizing CD. A brief overview of the surgical management of perianal fistulizing CD is also provided.

Discontinuation of Anti-Tumour Necrosis Factor Therapy in Patients with Perianal Fistulizing Crohn's Disease: Individual Participant Data Meta-Analysis of 309 Patients from 12 Studies.

The risk of relapse after anti-tumour necrosis factor [TNF] therapy discontinuation in Crohn's disease patients with perianal fistulas [pCD] is unclear. We aimed to assess this risk. A systematic literature search was conducted to identify cohort studies on the incidence of relapse following anti-TNF discontinuation in pCD patients. Individual participant data were requested from the original study cohorts. Inclusion criteria were age ≥16 years, pCD as a (co)indication for start of anti-TNF therapy, more than three doses, and remission of luminal and pCD at anti-TNF discontinuation. The primary outcome was the cumulative incidence of CD relapse using Kaplan-Meier estimates. Secondary outcomes included response to re-treatment and risk factors associated with relapse as assessed by Cox regression analysis. In total, 309 patients from 12 studies in ten countries were included. The median duration of anti-TNF treatment was 14 months [interquartile range 5.8-32.5]. Most patients were treated for pCD without active luminal disease [89%], received first-line anti-TNF therapy [87%], and continued immunomodulatory therapy following anti-TNF discontinuation [78%]. The overall cumulative incidence of relapse was 36% (95% confidence interval [CI] 25-48%) and 42% [95% CI 32-53%] at 1 and 2 years after anti-TNF discontinuation, respectively. Risk factors for relapse included smoking (hazard ratio [HR] 1.5 [1.0, 2.1]) and history of proctitis (HR 1.7 [1.1, 2.5]). The overall re-treatment response rate was 82%. This individual participant data meta-analysis, on predominantly patients with pCD without active luminal disease and first-line anti-TNF therapy, shows that over half of patients remain in remission 2 years after anti-TNF discontinuation. Therefore, anti-TNF discontinuation may be considered in this subgroup.

Internal Orifice Alloy Closure: A New Procedure for Treatment of Perianal Fistulizing Crohn's Disease.

BACKGROUND The high recurrence rate of perianal fistula Crohn's disease (PFCD) increases the need to protect the anal sphincter during each surgical treatment of fistulas. We aimed to evaluate the safety and efficacy of internal orifice alloy closure in patients with PFCD. MATERIAL AND METHODS Fifteen patients with PFCD were enrolled in the study between July 6, 2021, and April 27, 2023. All patients underwent preoperative colonoscopy and anal magnetic resonance examination for diagnosis and evaluation. Internal orifice alloy closure (IOAC) was performed only when Crohn's disease was in remission. The external sphincter had not been severed. Perianal magnetic resonance imaging examination was used for postoperative evaluation after 6 months. Fistula cure rate, length of stay, perianal pain, and Wexner incontinence score were retrospectively compared between 15 patients treated with IOAC and 40 patients treated with other surgical methods. RESULTS Fifteen patients (male/female: 9/6, age: 23.6±14.3 years) with PFCD were included (follow-up: 24 months). In total, 20.0% (3) had multiple tracts, and 13.3% (2) had a high anal fistula. Among them, 10 patients received biologics for induction for mucosal healing before surgery. The fistula healed completely in 80.0% (12/15) and did not heal in 20.0% (3/15). Three patients who did not heal underwent fistulotomy and eventually recovered. IOAC is not superior in terms of fistula healing rates, length of stay, and anal pain, but its Wexner incontinence scores are significantly lower than with other surgical methods. CONCLUSIONS IOAC is a novel sphincter-saving surgery that is effective and safe for the treatment of PFCD.

Diagnostic performance of texture analysis in the differential diagnosis of perianal fistulising Crohn’s disease and glandular anal fistula

Perianal fistulising Crohn's disease (PFCD) and glandular anal fistula have many similarities on conventional magnetic resonance imaging. However, many patients with PFCD show concomitant active proctitis, but only few patients with glandular anal fistula have active proctitis.To explore the value of differential diagnosis of PFCD and glandular anal fistula by comparing the textural feature parameters of the rectum and anal canal in fat suppression T2-weighted imaging (FS-T2WI).Patients with rectal water sac implantation were screened from the first part of this study (48 patients with PFCD and 22 patients with glandular anal fistula). Open-source software ITK-SNAP (Version 3.6.0, http://www.itksnap.org/) was used to delineate the region of interest (ROI) of the entire rectum and anal canal wall on every axial section, and then the ROIs were input in the Analysis Kit software (version V3.0.0.R, GE Healthcare) to calculate the textural feature parameters. Textural feature parameter differences of the rectum and anal canal wall between the PFCD group vs the glandular anal fistula group were analyzed using Mann-Whitney U test. The redundant textural parameters were screened by bivariate Spearman correlation analysis, and binary logistic regression analysis was used to establish the model of textural feature parameters. Finally, diagnostic accuracy was assessed by receiver operating characteristic-area under the curve (AUC) analysis.In all, 385 textural parameters were obtained, including 37 parameters with statistically significant differences between the PFCD and glandular anal fistula groups. Then, 16 texture feature parameters remained after bivariate Spearman correlation analysis, including one histogram parameter (Histogram energy); four grey level co-occurrence matrix (GLCM) parameters (GLCM energy_all direction_offset1_SD, GLCM entropy_all direction_ offset4_SD, GLCM entropy_all direction_offset7_SD, and Haralick correlation_all direction_ offset7_SD); four texture parameters (Correlation_all direction_offset1_SD, cluster prominence _angle 90_offset4, Inertia_all direction_offset7_SD, and cluster shade_angle 45_offset7); five grey level run-length matrix parameters (grey level nonuniformity_angle 90_offset1, grey level nonuniformity_all direction_offset4_SD, long run high grey level emphasis_all direction_offset1_SD, long run emphasis_all direction_ offset4_ SD, and long run high grey level emphasis_all direction_offset4_SD); and two form factor parameters (surface area and maximum 3D diameter). The AUC, sensitivity, and specificity of the model of textural feature parameters were 0.917, 85.42%, and 86.36%, respectively.The model of textural feature parameters showed good diagnostic performance for PFCD. The texture feature parameters of the rectum and anal canal in FS-T2WI are helpful to distinguish PFCD from glandular anal fistula.

P337 Developing Preliminary MRI-based Classifier for Perianal Fistulizing Crohn’s Disease by Using Deep Convolutional Neural Networks

Abstract Background Early diagnosis and management of perianal fistulizing Crohn’s disease (PFCD) is critical. But there is still lack of single reliable diagnostic modality to differentiate between early PFCD and cryptoglandular anal fistula (CAF). This study aimed to evaluate the feasibility and efficacy of deep convolutional neural networks (DCNNs) for distinguishing PFCD from CAF based on pelvic magnetic resonance imaging (MRI). Methods The MRIs from 400 patients primarily diagnosed with PFCD or CAF (two hundred respectively) were retrospectively collected as datasets and used in this study. All patients had no fistula associated surgical histories. The datasets were split into training (80%), validation (10%), and test(10%). Four different DCNNs, MobileNetV2, VGG11, ResNet18 and ResNet34, were trained to classify the patients with fistula MRIs as PFCD or as CAF. Both untrained and pretrained networks were used. Pretrained networks were obtained from the Pytorch Models, an open-access repository of pretrained models for use with Pytorch. The protocol was shown in Figure 1 and was approved by the institutional review board (2022ZSLYEC-421).On the test dataset, receiver operating characteristic curves and areas under the curve (AUCs) were used to assess model performances and were compared with the performances of radiologists. Comparisons between AUCs were made by using the Delong method. Accuracy, sensitivity, and specificity were determined from the optimal threshold by the Youden index. Figure 1. Results Compared with CAF, the PFCD dataset contained more high fistulas (59.5% vs. 44.5%，P=0.003), more fistulas involved in the deep anterior space (15.5% vs. 3.0%，P&amp;lt;0.001), and less abscess formation (32.5% vs. 59.5%，P&amp;lt;0.001). Other fistula characteristics including ramification formation, supra- or infralevator extension, were not statistically different. The performances of the pretrained models were better than that of the untrained models (Figure 2). The AUC of 4 pretrained DCNN classifiers were MobileNetV2 [AUC: 0.943，95%CI（0.820~0.991）], VGG11 [AUC: 0.935, 95%CI（0.810~0.988）], ResNet 18 [AUC: 0.920, 95%CI（0.789~0.982）], ResNet 34[AUC: 0.929, 95%CI（0.801~0.986）] respectively. The performances of 4 pretrained DCNN classifiers were equivalent to that of senior radiologist, and were superior to that of junior radiologist (Figure 2, 3, 4). Figure 2. Figure 3. Figure 4. Conclusion Deep learning with DCNN in classifying PFCD or CAF on perianal MRI is feasible. Transfer learning may further improve the performance of the DCNN model. A larger sample size dataset to train the former DCCNs is conducting in our constitution and the external validation will be added in the future.

Ustekinumab Promotes Radiological Fistula Healing in Perianal Fistulizing Crohn's Disease: A Retrospective Real-World Analysis.

There is insufficient evidence to confirm the efficacy of ustekinumab (UST) in promoting fistula closure in perianal fistulizing Crohn's disease (CD) patients. We aimed to evaluate the efficacy of UST in a real-world setting. The data were retrospectively analyzed. Intestinal clinical and endoscopic changes were evaluated. Fistula radiological outcomes were determined using the Van Assche score. A total of 108 patients were included, 43.5% of whom had complex perianal fistulas. Intestinal clinical and endoscopic remission was achieved in 65.7% and 31.5% of patients, respectively. The fistula clinical remission and response rates were 40.7% and 63.0%, respectively, with a significant reduction in Perianal Crohn's disease Activity Index [5.0(3.0, 8.0) vs. 7.5(5.0, 10.0), p < 0.001] and Crohn's Anal Fistula Quality of Life [23.5(9.3, 38.8) vs. 49.0(32.3, 60.0), p < 0.001]. Radiological healing, partial response, no change, and deterioration were observed in 44.8%, 31.4%, 13.4%, and 10.4% of patients, respectively. The cut-off UST trough concentration for predicting fistula clinical remission was 2.11 μg/mL with an area under the curve of 0.795, a sensitivity of 93.3%, and a specificity of 67.6%. UST is efficacious in promoting radiological fistula closure in patients with perianal fistulizing CD. A UST trough concentration over 2.11 μg/mL was correlated with a higher likelihood of perianal fistula clinical remission.

Effectiveness and safety of darvadstrocel in patients with complex perianal fistulizing Crohn's disease: a systematic review.

Managing complex perianal fistulizing Crohn's disease (CD) remains challenging, despite current medical and surgical treatment approaches. Darvadstrocel, a therapy utilizing adipose-derived stem cells, shows promise in promoting tissue regeneration and healing, offering a novel and effective treatment for fistula management. A systematic literature search was conducted on PubMed and Scopus to identify studies involving patients with complex perianal fistulizing CD treated with darvadstrocel. In total, 2 randomized controlled trials (RCT), 5 observational studies with retrospective data collection and 2 observational studies with prospective design were included in the final review. Data from the European ADMIRE-CD RCT demonstrated that darvadstrocel is superior to placebo in terms of clinical and imaging improvement over both the short and long term. These findings align with the prospective studies analyzed in this systematic review. The rate of treatment-emergent adverse events in the ADMIRE-CD trial's RCTs was similar in both the darvadstrocel and control groups, with perianal abscess being the most common adverse event up to 52 weeks after drug administration. Retrospective studies indicated no side-effects beyond 52 weeks. Darvadstrocel appears to be a new, potentially effective and safe treatment option for the management of complex perianal fistulas. However, more randomized clinical trials are needed to evaluate the efficacy and safety profile of the drug.