Perianal Crohn's Disease Research Articles

Establishing a rabbit model of perianal fistulizing Crohn’s disease

BACKGROUNDCrohn's disease (CD) is a chronic nonspecific intestinal inflammatory disease. The aetiology and pathogenesis of CD are still unclear. Anal fistula is the main complication of CD and is a difficult problem to solve at present. The main limitation of developing new therapies is bound up with the short of preclinical security and effectiveness data. Therefore, an ideal animal model is needed to establish persistent anal fistula and an inflamed rectal mucosa.AIMTo improve the induction method of colitis and establish a reliable and reproducible perianal fistulizing Crohn’s disease animal model to evaluate new treatment strategies.METHODSTwenty male New Zealand rabbits underwent rectal enema with different doses of 2,4,6-trinitrobenzene sulfonic acid to induce proctitis. Group A was treated with an improved equal interval small dose increasing method. The dosage of group B was constant. Seven days later, the rabbits underwent surgical creation of a transsphincteric fistula. Then, three rabbits were randomly selected from each group every 7 d to remove the seton from the fistula. The rabbits were examined by endoscopy every 7 days, and biopsy forceps were used to obtain tissue samples from the obvious colon lesions for histological analysis. The disease activity index (DAI), colonoscopy and histological scores were recorded. Perianal endoscopic ultrasonography (EUS) was used to evaluate the healing of fistulas.RESULTSExcept for the DAI score, the colonoscopy and histological scores in group A were significantly higher than those in group B (P < 0.05). In the ideal model rabbit group, on the 7th day after the removal of the seton, all animals had persistent lumens on EUS imaging, showing continuous full-thickness high signals. Histological inspection of the fistula showed acute and chronic inflammation, fibrosis, epithelialization and peripheral proctitis of the adjoining rectum.CONCLUSIONThe improved method of CD colitis induction successfully established a rabbit perianal fistula CD preclinical model, which was confirmed by endoscopy and pathology.

Invasive squamous cell carcinoma arising from long‐lasting enterocutaneous fistula due to Crohn's disease

Chronic inflammation led to squamous cell carcinoma. We experienced squamous cell carcinoma from Crohn’s disease. A 53-year-old woman with Crohn's disease (CD) diagnosed more than 30 years earlier was referred to us because of a 4 month history of abdominal tumors. She underwent a total colectomy, small intestinal resection, and an eternal enterostomy 24 years earlier and had two enterocutaneous fistulous tracts with repeated inflammation on the lower-right side of her abdomen for 13 years. She had been treated with 5-aminosalicylic acid for more than 15 years, but did not receive immunosuppressants or tumor necrosis factor alpha inhibitors. Physical examination revealed a 6 × 3.5 cm reddish ulcerative tumor on the lower-right side of her abdomen surrounded by brownish pigmentation with indurations (Figure 1A). Histopathological examination of the tumor revealed atypical squamous cell proliferation with marked keratinization (Figure 1B,C). Histological continuity between the epidermis and atypical cells was not observed, and immunostaining of the cells was negative for human papillomavirus. Computed tomography and positron emission tomography/computed tomography demonstrated a large mass involving the abdominal walls and enlargement of the inguinal and right external iliac lymph nodes (Figure 1D). Her serum squamous cell carcinoma (SCC) antigen level was also elevated (5.4 ng/ml; normal range, <2.5 ng/ml). The patients were then diagnosed with SCC arising from an enterocutaneous fistula (ECF) related to CD. She was treated with radiation therapy (30 Gy) for a skin tumor and bilateral inguinal lymph nodes, followed by chemotherapy with pepleomycin. Unfortunately, her disease slowly progressed and she died 5 months after her initial visit. Crohn's disease is a chronic inflammatory bowel disorder characterized by transmural inflammation and fistula formation.1 Perianal fistulas are common complications of the disease, and patients with anal and/or perianal CD have a high risk of perianal fistula-related cancer.2 Fistula-related carcinoma develops in approximately 1% of patients with fistulizing perianal CD. More than half of these carcinomas are adenocarcinoma; most of the rest are SCC. Compared with perianal fistulas, ECF is rare, but it is associated with significant morbidity and mortality due to various complications.3 Late complications, such as late onset of malignancy, have been given little attention in the literature, with a limited number of patients with cancers arising from ECF and only one fistula-associated SCC patient, who was treated with long-lasting azathioprine followed by infliximab, being reported.4 The causes of malignancies arising from chronic fistulas are unclear, but chronic inflammation and immunosuppression are considered mechanisms of carcinogenesis in CD patients. Chronic inflammation, a feature of CD, induces constant epithelial regeneration, ulceration, and high cell turnover rates, leading to dysplasia and subsequently carcinoma. Our patient was not treated with immunosuppressants or biologics; however, so it is likely that her chronic inflammation led to carcinogenesis. The onset of malignancies arising from ECF in CD patients may increase in future because of the expanding use of immunosuppressants and/or biologics and improvements in the treatment of acute complications of ECF. Therefore, diagnosticians should be alert to early signs of fistula-associated malignancies. The authors declare no conflict of interest. Approval of the research protocol: N/A. Informed Consent: The written informed consent was obtained from the patient. Registry and the Registration No. of the study/trial: N/A. Animal Studies: N/A.

Therapeutic drug monitoring in inflammatory bowel disease: At the right time in the right place.

Therapeutic drug monitoring (TDM) was one of most sought-after objective tools to determine therapeutic efficiency of different biologics and its role in the management of patients with inflammatory bowel disease (IBD) was regarded with great anticipation. But implementation of the TDM in clinical practice was challenged by several factors including uncertainty of the optimal cut-off values, assay variable sensitivity in detecting drug levels and antibodies and, most importantly, individual pharmacokinetics. While reactive TDM was embraced in clinical practice as a useful tool in assessing lack of response to therapy, the utility of proactive TDM in managing IBD therapy is still challenged by the lack of consistency between evidence. Described here, there are four groups of IBD patients for whom proactive TDM has the potential to greatly impact their therapeutic outcomes: Patients with perianal Crohn’s disease, patients with severe ulcerative colitis, pregnant women with IBD and children. As the future of IBD management moves towards personalizing treatment, TDM will be an important decision node in a machine learning based algorithm predicting the best strategy to maximize treatment results while minimizing the loss of response to therapy.

Anti TNF treatment of complex perianal fistulas in children without luminal Crohn's disease: Is it an option?

ObjectivesComplex perianal fistulas (CPFs) in children even in the absence of luminal symptoms prompt evaluation for Crohn's disease (CD). Reports of isolated CPF in children, however, are sparse. In perianal CD, antitumor necrosis factor α (anti TNF) therapy is recommended. We aimed to describe our experience with anti TNF therapy in children with isolated CPF without evidence of luminal CD. MethodsWe retrospectively reviewed charts of patients with isolated CPF who were treated with anti TNF agents between 2011 and 2019 in a tertiary center. MRI pelvis findings at baseline versus end of follow up were scored using MAGNIFI-CD. Outcomes included clinical remission, radiological response and radiological remission based on MAGNIFI-CD score at end of follow up. ResultsOverall, 17 patients were identified, [10 males (59%), mean age at anti TNF initiation 13.4 ± 2.9 years]. Median time from perianal disease onset to anti TNF was 16.5 months (IQR 9.4–36.4). None of the patients had luminal inflammation. Prior to anti TNF, all patients had been treated with antibiotics without sufficient improvement, and 9/17 with abscess drainage and or Seton insertion. Nine patients (53%) were treated with infliximab while 8 (47%) received adalimumab. Median duration of follow up was 30.7 months (IQR = 12.7–44.8). At the end of follow up 9 patients (53%) achieved clinical remission. When comparing MRI prior to and after anti TNF, 36% (5/14) had radiologic response, of whom 2 (14%) achieved radiologic resolution. ConclusionAnti TNF agents may be an effective treatment option for children with isolated CPF. Whether these patients should be considered part of the CD phenotypic spectrum or a distinct entity is unclear. Levels of EvidenceTherapeutic.

Is There a Best First Line Biological/Small Molecule in IBD: Are We Ready for Sequencing?

Inflammatory bowel disease (IBD) is a chronic, life-long inflammatory condition of the gastrointestinal tract. Treatment strategy depends on the severity of the disease course. IBD physicians need to be aware of the life-long treatment options available. The goal is not only to achieve clinical remission but to halt or stabilize the chronic inflammation in the intestines to prevent further structural damage. Therefore, the use of early biologic therapy is recommended in moderate-to-severe IBD patients. However, in the last decade, use of therapeutic drug monitoring has increased considerably, opening an opportunity for sequencing. This review summarizes the available evidence on biologic and small molecules therapy in Crohn’s disease (CD) and ulcerative colitis (UC) in different clinical scenarios, including perianal CD, the elderly, extra intestinal manifestations, and pregnancy.

Características clínicas y tratamiento de la enfermedad de Crohn perianal fistulizante en Colombia: resultados de un registro multicéntrico

IntroductionPerianal fistulizing Crohn's disease (CD) is a phenotype with a poor prognosis. There are no studies in our country. Our objective is to determine the clinical, sociodemographic and treatment characteristics of perianal fistulizing CD in a Colombian multicenter registry. Materials and methodsA retrospective, multicenter observational study was carried out, with prospective data collection, in the main reference centers for inflammatory Bowel disease (IBD) in the country. Continuous variables were expressed as medians and interquartile ranges. The categorical outcome variables were compared by the Chi-square test. ResultsSixty-five patients with perianal fistulizing CD were documented, with a median age of appearance of perianal fistula of 31.0 years (range: 24-42), predominantly in men (61.5%; H:M ratio: 1.4:1). Complex perianal fistulas were more frequent than simple ones (75.35 vs. 24.6%). Regarding medical treatment, 66.2% of the patients received antibiotics, 64.6% steroids, 78.5% biological therapy, 47.7% non-cutting setons, and 46.2% required surgical management, other than seton placement. Only 29.2% achieved complete remission of the fistula, and 9.2% of the patients ended up in a definitive colostomy. CD patients with complex fistulas received more biological therapy, compared to CD patients with simple fistulas (84.8 vs. 56.3%; P: 0.038). ConclusionsPerianal fistulizing CD has a poor prognosis in our setting, only 3 out of 10 patients achieve complete remission despite treatment. A multidisciplinary management is essential for the comprehensive management of this difficult pathology.

Perianal Imaging in Crohn Disease: Current Status With a Focus on MRI, From the AJR Special Series on Imaging of Inflammation.

Fistulizing perianal disease, a frequent, chronic, and often debilitating manifestation of Crohn disease (CD) in adults and children, has been relatively refractory to treatment in the past. The advent of biologic agents such as anti-tumor necrosis factor-α and cellular therapies, used in conjunction with a range of surgical interventions, has greatly improved disease outcomes, although complete remission can still be elusive. This Special Series review considers current perianal imaging options, specifically pelvic MRI and endoanal and transperineal ultrasound, as well as their roles in the diagnosis, management, and assessment of treatment response. Pelvic MRI is the first-line modality for imaging perianal CD, given the complexity of fistulas encountered in CD. MRI technical acquisition parameters for adults and children and an approach to MRI interpretation and reporting are provided. Anatomic classification systems for fistulizing peri-anal disease are presented. We also explore the history, current landscape, and future developments of MRI features of perianal disease as imaging biomarkers, to quantify activity and severity and to consider CD MRI-based inflammatory activity scores. We discuss the reliability and validation of a number of indexes (including the pediatric MRI-based perianal CD [PEMPAC] index, the MR novel index for fistula imaging in CD [MAGNIFI-CD], the Van Assche index, and the modified Van Assche index), their potential to quantify treatment response, and possible prognostic capabilities.

A Microbial Signature for Paediatric Perianal Crohn's Disease.

Perianal fistulising disease can affect up to 25% of patients with Crohn's disease [CD] and lead to significant morbidity. Although the role of the gut microbiota in inflammatory bowel disease [IBD] has been increasingly recognised, its role in fistula development has scarcely been studied. Here, we aimed to define the microbial signature associated with perianal fistulising CD in children. A prospective observational study including children age 6-18 years with a diagnosis of perianal fistulising CD was conducted. Stool samples and rectal and perianal fistula swabs were collected. Stool samples and rectal swabs from children with CD without perianal disease and healthy children were included as comparison. Whole shotgun metagenomic sequencing was performed. A total of 31 children [mean age 15.5 ± 3.5 years] with perianal CD were prospectively enrolled. The fistula-associated microbiome showed an increase in alpha diversity and alteration in the abundance of several taxa compared with the rectal- and faecal-associated microbiome with key taxa belonging to the Proteobacteria phylum. Genes conferring resistance to the clinically used antibiotic regimen ciprofloxacin and metronidazole were found in the three sample types. In comparison with children without the perianal phenotype [N = 36] and healthy controls [N = 41], the mucosally-associated microbiome of children with perianal CD harboured a reduced butyrogenic potential. Linear discriminant analysis identified key taxa distinguishing the rectal mucosally-associated microbiome of children with perianal CD from children without this phenotype. The microbial community within CD-related anorectal fistula is compositionally and functionally unique. Taken together, these findings emphasise the need to better understand the ecosystem of the fistula milieu to guide development of novel microbiome-based strategies in this CD phenotype.

Perianal Crohn Disease Is More Common in Children and Is Associated With Complicated Disease Course Despite Higher Utilization of Biologics: A Population-based Study From The epidemiology group of the Israeli IBD Research Nucleus (epiIIRN).

Both perianal and pediatric-onset Crohn disease (CD) disease are associated with complicated disease course and higher drug utilization. we aimed to explore the differences between pediatric and adult-onset perianal CD and their disease course. We included all patients with newly diagnosed CD from 2005 to 2019 at two Israeli Health Maintenance Organizations, covering 78% of the population. A combination of ICD-9 codes, radiology and procedures was used to define fistulizing perianal CD (PCD) and its severity according to the association with simple and complex perianal disease. A total of 12,905 patients were included (2186 [17%] pediatric-onset, 10,719 [83%] adults), with a median follow-up of 7.8 years. PCD was diagnosed in 1530 (12%) patients, with higher incidence in children (308 [14%] children vs 1222 adults [11%]; P < 0.001). Children had higher incidence of severe PCD (141/308 [47%] vs 433/1222 [35%]; P < 0.001). At 5 years, children with PCD were more likely than adults to be treated with biologics (212 [69%] vs 515 [42%]; odds ratio [OR] 2.6 [95% confidence interval (CI) 1.6-4.0]; P < 0.001) and immunomodulators (238 [74%] vs 643 [53%]; OR 2.8 [95% CI 2.1-3.6]; P < 0.001). PCD in children was still associated with poorer disease outcomes as shown for surgeries (36 [12%] vs 93 [8%]; P = 0.02) and steroid-dependency (52 [17%] vs 156 [13%]; P < 0.001). Multivariable modeling indicated that the severity of PCD is a stronger predictor of disease course than age. PCD is more common in pediatric-onset CD and is associated with higher drug utilization and worse disease outcomes, in large due to higher rate of severe PCD in children.

A148 IMPACT OF EXAMINATION UNDER ANESTHESIA PRIOR TO ANTI-TUMOR NECROSIS FACTOR THERAPY ON FISTULA HEALING FOR PERIANAL CROHN’S DISEASE PATIENTS: A COMPARATIVE COHORT STUDY

Abstract Background Current guidelines recommend a combined approach consisting of an examination under anesthesia (EUA) and anti-TNF therapy for perianal Crohn’s Disease (PCD). However, the impact of this approach on fistula healing and long-term outcomes is unknown. Aims To assess the effect of EUA on fistula healing and long term outcomes in patients with perianal Crohn’s disese who are treated with anti-TNF therapy. Methods We performed a retrospective, single-center, comparative cohort study between 2009 and 2019. We compared patients with PCD who received EUA prior to anti-TNF therapy (combined therapy) to anti-TNF therapy alone. Our primary outcome was fistula closure by clinical assessment. Secondary outcomes included subsequent local surgery and fecal diversion. Logistic regression and multivariable cox-proportional hazard models adjusted for abscesses, concomitant immunomodulators, and time to anti-TNF initiation were performed. Results A total of 155 patients underwent 188 distinct anti-TNF starts: 66 (35%) after an EUA. Patients who underwent an EUA prior to anti-TNF therapy were more likely to have an abscess (50% vs. 15%; p &amp;lt; 0.001) and concomitant immunomodulator usage (64% vs. 50%; p = 0.07). Otherwise, there were no differences between cohorts in age, smoking status, disease duration, and location of luminal disease. There were no significant differences in fistula closure at 3, 6, or 12 months between cohorts overall (Table 1). The results remained consistent in sensitivity analyses that excluded patients with abscesses and prior biologic treatment failure. The results were also similar when defining the combined therapy group as those with setons. After a median follow-up of 4.6 years (IQR, 5.95) patients who underwent an EUA prior to anti-TNF therapy were more likely to require a subsequent EUA (aHR 2.2; 95% CI, 1.3–3.6) (Figure 1) but not fecal diversion (aHR 1.3; 95% CI, 0.45–3.9). Conclusions In this single center study, combined therapy (EUA prior to anti-TNF therapy) was not associated with improved clinical outcomes compared with anti-TNF therapy alone. These findings suggest that EUA may not be necessary in every patient with PCD prior to initiation of anti-TNF therapy. Future prospective studies that control for fistula complexity are warranted. Table 1: Unadjusted rates of fistula closure after anti-TNF therapy comparing patients with and without an exam under anesthesia Funding Agencies University of Ottawa Department of Medicine

Vedolizumab for perianal fistulizing Crohn's disease: systematic review and meta-analysis.

Background/AimsPerianal fistulas are a debilitating manifestation of Crohn’s disease (CD). Despite the advent of anti-tumor necrosis factor (anti-TNF) therapy, the medical management of fistulizing CD continues to be challenged by unmet needs. We conducted a systematic review and meta-analysis of the effectiveness of vedolizumab for the management of perianal fistulizing CD.MethodsA search of PubMed, EMBASE and the Cochrane Library was performed from inception to June 2020 for studies reporting rates of perianal fistula healing in CD patients treated with vedolizumab. The primary outcome of interest was complete healing of perianal fistulas and the secondary outcome was partial healing. The pooled fistula healing rates with 95% confidence intervals (CI) were calculated utilizing a random effects model.ResultsA total of 74 studies were initially identified, 4 of which met the inclusion criteria. A total of 198 patients with active perianal fistulas were included, 87% of whom had failed previous anti-TNF therapy. The pooled complete healing rate was 27.6% (95% CI, 18.9%–37.3%) with moderate heterogeneity (I2=49.4%) and the pooled partial healing rate was 34.9% (95% CI, 23.2%–47.7%) with high heterogeneity (I2=67.1%).ConclusionsIn a meta-analysis of 4 studies that included 198 patients with perianal fistulizing CD, the majority of whom had failed previous anti-TNF therapy, vedolizumab treatment led to healing of perianal fistulas in nearly one-third of the patients. The lack of high-quality data and significant study heterogeneity underscores the need for future prospective studies of fistula healing in patients receiving anti-integrin therapy.

Stem Cell Injection for Complex Refractory Perianal Fistulas in Crohn's Disease: A Single Center Initial Experience.

From 30 to 70% of patients with Crohn's disease (CD) may develop perianal fistulas during their lifetime. The medical and surgical management of this complication is challenging, and its treatment still gives unsatisfactory results. However, recent studies on adipose-derived mesenchymal stem cells have proven their anti-inflammatory and immuno-modulatory potential, representing a new promising tool in the treatment of such stubborn disease. We report our initial experience with three patients who had recurrent perianal CD treated with local infiltration of stem cell darvadstrocel (Alofisel). All the patients had a long history of perianal disease refractory to multiple medical and surgical treatments. The preoperative workup included transperineal ultrasound (TP-US), pelvic MRI, and colonoscopy that ruled out active proctitis in all the patients. The post-treatment follow-up included clinical assessment at 1, 3, and 6 months with repeated MRI and TP-US at 6 months. At 6 months, 2 patients had a clinical response despite radiological persistence of fistula tracts, while one patient presented perianal fistula recurrence complicated by perianal abscess. Although our experience is limited to 3 patients and a short follow-up, our results confirm that darvadstrocel injection is a safe procedure, with a good clinical response in most of the patients, but that it apparently had no effect on the anatomical modification of the fistula tracts. Long-term results, with a rigorous assessment of anatomical lesions, are still needed to support the promising data of the literature.

Impact on Quality of Life of Seton Placing in Perianal Crohn's Disease

IntroductionOften, in perineal Crohn's disease (CD), a seton is placed to guarantee a constant drainage and prevent septic complication while biologic therapy is ongoing. This study aimed to assess the long-term quality of life after surgery for perineal CD in relation to seton placing.Patients and MethodsData of 65 consecutive patients with CD and non-CD operated on from 2014 to 2019 for perianal fistula or abscess were retrieved. Forty-three had CD and 14 of them had a seton placed during surgery and they kept it on while they had anti-TNF-alpha therapy. Patients were interviewed with the Cleveland Global Quality of Life (CGQL) and SF-12 quality of life questionnaires. Disease activity was defined as Harvey-Bradshaw Index (HBI) and Perianal Disease Activity Index (PDAI). Comparisons between groups were carried out with the nonparametric tests, and multiple regression models were used to assess predictors of quality of life.ResultsThe total CGQL score and SF-12 mental component score (MCS) were significantly higher (and thus better) in the seton group than in patients treated without seton. On the contrary, SF-12 physical component score (PCS) was not different between the two groups. HBI was significantly better in patients in the seton group. At multivariate analysis, seton placement and HBI were confirmed to be independent predictors of long-term SF-12 MCS whereas only HBI confirmed to be a predictor of total CGQL score.ConclusionsSeton placing during anti-TNF-alpha therapy is independently associated with a better MCS. Unexpectedly, this device, instead of to cause psychological distress, seems to assure patients during their biologic therapy providing psychological benefit beyond the mere medical effect.

OP19 Classifying perianal fistulising Crohn’s Disease: An expert-consensus to guide decision-making in daily practice and clinical trials

Abstract Background Perianal fistulising Crohn’s disease (CD) is an aggressive disease phenotype that can have a significant impact on patients’ quality of life. Current biological understanding of perianal fistulising CD remains inadequate and previous classification systems have not provided clear guidance on therapy in clinical practice nor on defining patient cohorts within clinical trials. To counter this unmet need, we propose a new classification system for perianal fistulising CD. Methods The proposed classification system was developed through a modified nominal group technique expert consensus process involving open discussion and formal voting on previously defined statements. Consensus agreement was defined a priori as 80% voting “strongly agree” or “agree with minor reservation”. Participants included gastroenterologists, radiologists, surgeons active in a tertiary IBD centre and a patient representative. Results The classification identifies four groups of patients with perianal fistulising CD. Key elements include stratification according to disease severity as well as disease outcome; synchronisation of patient and clinician goals in decision making, with a proactive, combined medical and surgical approach, on a ‘treat to patient goal’ basis; and identification of indications for curative fistula treatment, diverting ostomy and proctectomy. The new classification retains an element of flexibility, in which patients can cycle through different classes over time. Furthermore, with each specific class comes a paired treatment strategy suggestion and description of clinical trial suitability. Conclusion The proposed classification system is the first of its kind and is an important step towards tailored standardisation of clinical practice and research in patients with perianal fistulising CD.

P197 Anogenital Crohn’s disease and granulomatosis: A systematic review of epidemiology, clinical manifestations, and treatment

Abstract Background Metastatic Crohn’s disease (CD) is an extra-intestinal manifestation (EIM) characterised by ulceration, swelling or inflammatory lesions that are non-contiguous with the gut; genital involvement is rare. We conducted a systematic review of ACD and granulomatosis to provide a synthesis of epidemiology, clinical features, and treatment outcomes in adults and children. Methods A systematic literature search was conducted via MEDLINE, EMBASE and the Cochrane database from inception to 1st December 2020 to identify studies of ACD presentation and/or treatment outcomes. Investigators extracted, analysed, and reported study data in accordance with PRISMA. Clinical response was defined as a reduction in symptoms, genital swelling or partial healing of ulcers and fissures. Remission was defined as complete resolution of symptoms and examination findings. Results Of 9,381 screened studies, 185 articles, (comprising 410 cases; 273 female (F), 137 male (M)), were included (figure 1). The median age at diagnosis was 29 (F) and 16 (M) and up to 50% did not have a prior CD diagnosis. Luminal CD was subsequently diagnosed in 80% of cases including 45–80% patients without gastrointestinal symptoms (time to CD diagnosis from ACD presentation [range] –43 to 11 years). The predominant clinical features across both sexes were, oedema (79%), ulcers/fissures (47%), and hypertrophic, exophytic lesions (nodules and plaques) (23%) (table 1). Adults and children present similarly. Most patients, 81% (331/410), underwent genital biopsy (106 (M), 225 (F)). Granulomas were noted in 71% (234/331) cases and an inflammatory cell infiltrate was documented in 191/331 (58%). Systemic antibiotics, corticosteroids, thiopurines and anti-TNF therapy were the most frequently prescribed agents with the highest response and remission rates (table 2). At final follow-up, where reported, non-response, response, and remission rates were 37/304 (12%), 267/304 (88%) and 114/304 (38%), respectively. Oedema was associated with a poor response to topical corticosteroids vs. those with ulcers or fissures without oedema (p=0.03). Greater response rates to anti-TNF therapy were seen in patients prescribed concomitant immunomodulation (24/25, 96% vs 67/90, 74%, p=0.02). Conclusion To our knowledge this is the first systematic review of ACD in adult and paediatric males and females. ACD and granulomatosis are rare EIMs of CD that are under-recognised, leading to treatment delay, and significant morbidity. There is a wide heterogeneity in presentation and some of the treatments used in luminal and perianal CD appear to be effective. Further studies with longer follow up are required to define optimal treatment strategies.

DOP31 Efficacy and safety of bone marrow-derived mesenchymal stem cells in refractory perianal fistulae in Crohn’s Disease: Results from a prospective monocentric study

Abstract Background Anoperianal lesions affect up to 30% of patients with Crohn’s disease (CD). Long-term fistula healing is challenging with conventional biotherapies. Although recent studies demonstrated the efficacy of local injections of adipose tissue-derived stem cells with 50 % of fistulae closure without abscess at one year, this treatment is not available in routine. The primary aim of this study was to evaluate the safety and the feasibility of the injection of bone marrow-derived mesenchymal stem cells isolated and prepared in a local university laboratory of cell therapy for perianal fistulizing CD. The second aim was to evaluate the efficacy of this treatment and his impact on the quality of life of the patients. Methods A prospective observational study was performed in the CHU of Liège from October 2019 till October 2021. All CD patients with perianal fistula and seton placement for at least 6 months were eligible. PRO, clinical examination, CRP, fecal calprotectine, CDAI, Short health scale (SHS) and MRI were performed at weeks 0, 12 and 48. PDAI was calculated at inclusion and at Week 48. Efficacy was defined as closure of all treated external openings at clinical examination without abscess at MRI. Results Sixteen patients with a median age of 49 years old and a median duration of perianal CD of 8 years were included. Eleven (69%) patients were on anti-TNF. CDAI and PDAI at inclusion were 97,5 ± 48,8 et 5 ± 4,4 respectively. Four (25%) patients reported adverse events the week after the injection (local pain 3/16, mild bleeding 1/16), all of them quickly resolutive. Ten (63%) and 8 (50%) patients had a closure of all the external opening at week 12 and 48 respectively. Five out of 6 patients with 2 external openings had at least 1 opening closed at Week 48. One abscess was observed during the follow-up. The median PDAI was numerically lower at the end of the study (3 versus 5 at the inclusion). The quality of life improved with a regression of the SHS from 10 to 7.5 at the end of the follow-up. At MRI, MAGNIFI-CD score and Van Assche index were similar for each patients at the inclusion and at the end of the study. Conclusion Injection of locally prepared bone marrow-derived mesenchymal stem cells seems safe and effective in refractory perianal fistulae in Crohn’s disease with 50% of closure at 1 year. The treatment is associated with an improvement of the perianal activity scores and the quality of life scores but not with the MRI scores.

Evaluation of the efficacy and safety of transplantation of adipose-derived stem cells in the treatment of refractory fistulizing Crohn's disease

Aim: The treatment of perianal fistulas in Crohn's disease (CD) is a challenge. Adipose-derived stem cells (ADSCs) are an option for treating fistulas, but their behavior at the injection site still needs to be further investigated. The efficacy and safety of autologous transplantation of ADSCs of patients with refractory perianal fistulizing CD was evaluated. Method: A total of 6 patients (18-48 years) were recruited. The intervention was three applications of autologous ADSCs (total of 3x107 cells). The evaluations happened in the 12th and 24th week after the first application, been considered primary and secondary efficacy outcomes, safety outcomes, anthropometric and food quality assessments. Results: Three patients completed the study and been treated 8 fistulas with ADSCs, none application-related effect was observed. The healing closure of the external part occurred in four fistulas, with local reepithelialization, and also two closed completely in the 12th week. The Van Assche index indicates improvement in only one of the patients. On the other hand, the Clinical Perianal Disease Activity Index and the quality of life assessment indicated progress for the three patients until the end of the study. By the CD Simple Endoscopic Score, two patients had the disease endoscopically inactive at the end of follow-up. Most of the anthropometric measurements were adequate and the foods that had low consumption throughout the study, in conformity for the three evaluated, were those belonging to the group of beans. Conclusion: It is concluded that autologous ADSCs have clinical potential to safely treat refractory perianal fistulizing CD.

Fecal Diversion in Complex Perianal Fistulizing Crohn's Disease.

Complex perianal Crohn's disease (CD) remains a challenging problem. Fecal stream is thought to be a trigger of disease progression in patients with CD. In patients with refractory perianal CD, diversion of fecal stream is sometimes required to alleviate clinical symptoms when medical and local surgical management are unsuccessful. Several studies evaluated the outcomes of fecal diversion for complex perianal CD. After fecal diversion, the majority of patients achieved early clinical response, but the prospect of restoring bowel continuity was low (approximately 20%). Nearly half of the patients eventually required proctectomy. A number of studies attempted to identify predictive factors for the outcomes of fecal diversion. Only rectal involvement was associated with unsuccessful restoration of bowel continuity. Biologic therapy did not seem to improve the efficacy of fecal diversion, although the evidence level was low because of insufficient data or methodological limitations. Based on these results, fecal diversion may be useful in alleviating clinical symptoms related to severe perianal CD and avoiding immediate proctectomy. The impact of biologic therapy on the outcomes of fecal diversion should be further investigated.

Anorectal Strictures in Complex Perianal CD: How to Approach?

Anorectal strictures are a notoriously difficult to treat phenotype of perianal Crohn's disease. Quality of life is diminished due to ongoing pain, incontinence, difficulty with stool evacuation, and recurrent medical and surgical treatments. Medical therapy is aimed at treating luminal disease and mucosal ulceration to prevent worsening of fibrosis. Clinical examination and endoscopic intervention can be used for serial dilations of strictures. Unfortunately, despite optimal medical therapy and endoscopic intervention with serial anal dilations, surgery with intestinal diversion or proctocolectomy may be required as part of the treatment algorithm in a significant proportion of patients.

A Multi-Disciplinary Approach to Perianal Fistulizing Crohn's Disease.

Perianal fistulizing Crohn's disease represents a severe phenotype associated with significant morbidity. Patients with perianal fistulizing disease are more likely to have a severe disease course and have significant reductions in quality of life. Moreover, these patients are at risk for the development of distal rectal and anal cancers. Given the complexity and severity of this patient group, the management of perianal Crohn's disease must be undertaken by a multidisciplinary team. The gastroenterologist and colorectal surgeon play a critical role in the diagnosis and management of perianal fistulizing disease. An examination under anesthesia provides critical information and is an essential part of the work-up of complex perianal fistulas. The radiologist also plays a central role in characterizing anatomy and assessing response to treatment. Several imaging modalities are available for these patients with magnetic resonance imaging as the imaging modality of choice. Perianal disease developing after ileal pouch-anal anastomosis represents a particularly challenging form of fistulizing disease and requires a multidisciplinary clinical and radiologic approach to differentiate surgical complications from recurrent Crohn's disease.