Crohn's Fistulas Research Articles

Surgical Management of Enterovesical Fistula in Crohn's Disease in the Biologic Era.

Lay SummaryEnterovesical fistula in Crohn’s disease that require surgery may be managed safely laparoscopically with similar morbidity to open repair and a shorter length of stay. Preoperative biologic exposure does not affect surgical morbidity.

Gleaning insight from the PISA trials

The PISA studies represent a shift in our understanding of the difficulties in treating and studying perianal fistulae in Crohn's disease. In the PISA I trial,1 patients were randomly assigned to one of three groups: seton treatment alone, anti-TNF treatment for a year with seton removal at 6 weeks, and surgical closure after anti-TNF induction with cessation of treatment after 4 months. The trial had been designed to show that earlier findings, suggesting similar closure rates (of around 50%) with all three techniques, would make seton drainage the cheapest way to obtain the same outcome.

Mucinous adenocarcinoma in perianal fistula in Crohn's disease: Case report and literature review.

SummaryIntroduction and importanceCrohn's disease (CD) is a chronic bowel disease that, due to exacerbated inflammation, can lead to complications such as the development of perianal fistulas. The development of mucinous adenocarcinoma in perianal fistulas in patients with CD is rare and, consequently, few reports exist in the literature.Case presentationWe report the case of a 71-year-old man diagnosed 22 years ago with CD with perineal involvement, who came with complaints of intense perianal pain, a gluteal mass, and local bleeding. Tomography of his abdomen showed an expansive, heterogeneous, and solid perianal mass on the right, with interspersed necrotic/liquefied areas and possible mucinous content. The patient was referred to the surgery department for an incisional biopsy, which confirmed mucinous adenocarcinoma. The patient underwent extra levator abdominoperineal rectal resection (APR) with partial prostatectomy.Clinical discussionPerineal mucinous adenocarcinoma arising in a fistula associated with CD is very rare. Since the symptoms overlap, early diagnosis of malignancy is difficult. Histological analysis is the gold standard for its diagnosis. Surgical resection through APR is well-established and, despite being a complex procedure with potential complications, tends to have good results. However, the locoregional and inguinal lymph node involvement was related to a worse progression in this case.ConclusionThe diagnostic hypothesis of mucinous adenocarcinoma should be suspected in CD patients who present long-term perineal involvement with fistulas. Biopsies and imaging exams should be performed to aid the diagnosis of the condition and thus contribute to the surgical plan.

Treatment of perianal fistulae in crohn's disease with mesenchymal stem cells

Crohn's disease is a chronic syndrome of the gastrointestinal tract that produces idiopathic inflammation. Approximately half of the patients develop abscesses and/or fistulas throughout their history that are located, mainly, in the perianal region. Current treatments are based on individualized plans that generally use combined pharmacology for symptomatic relief based on glucocorticoids, immunosuppressants or immunomodulators, antibiotics, anti-inflammatories, probiotics, and antibodies, or surgical therapies such as intestinal resections or ostomizations (colostomy and ileostomy) that tend to cause notable side effects in a considerable percentage of patients and a significant decrease in their quality of life. Perianal fistulas consist of abnormal tracts, inflammatory tunnels, or chronic tracts of granular tissue that connect two surfaces lined with epithelium, have an external hole in the skin that borders the anus, and an internal hole located inside it around the anal canal, rectus and sphincters. Treatment is a complex process that requires a multidisciplinary approach and the combination of several treatments. In the short term, the goal is to drain abscesses, reduce inflammatory and infectious processes, guard the fistulous tract with seton or lax lines, facilitate patency, and hinder new formations. In the long term, a total cure and the avoidance of complications that require surgery or the creation of intestinal stomas are pursued. For this reason, new effective remedies with fewer adverse effects continue to be investigated, one of the most promising being the use of mesenchymal stem cells for the regeneration and cure of perianal fistulas and the remission of symptoms. The present bibliographic review delves into this new therapy and analyzes the current state of the situation regarding its efficacy and safety.

Prevalence, diagnosis, and surgical management of complex ileocolic-duodenal fistulas in Crohn's disease.

The aim of the present study was to review the prevalence and surgical management of patients with Crohn's disease (CD) complicated by ileocolic-duodenal fistulas (ICDF). We performed a retrospective chart review of CD patients who underwent surgical takedown and repair of ICDF during January 2011-December 2021 at two inflammatory bowel disease referral centers. We identified 17 patients with ICDF (1.3%) out of 1283 CD patients who underwent abdominal surgery. Median age was 42 (20-71) years, 13 patients were male (76%) and median body mass index was 22.7 (18.4-30.3) kg/m2. Four patients (24%) were diagnosed preoperatively and only 2 (12%) were operated on for ICDF-related symptoms. The most common procedure was ileocolic resection (13 patients, 76%) including 4 repeat ileocolic resections (24%). The duodenal defect was primarily repaired in all patients with no re-fistulization or duodenal stenosis, regardless of the repair technique. A laparoscopic approach was attempted in the majority of patients (14 patients, 82%); however, only 5 (30%) were laparoscopically completed. The overall postoperative complication rate was 65% including major complications in 3 patients (18%) and 2 patients (12%) who required surgical re-intervention for abdominal wall dehiscence and postoperative bleeding. Preoperative nutritional optimization was performed in 9 patients (53%) due to malnutrition. These patients had significantly less intra-operative blood loss (485 vs 183ml, p = 0.05), and a significantly reduced length of stay (18 vs 8days, p = 0.05). ICDF is a rare manifestation of CD which may go unrecognized despite the implementation of a comprehensive preoperative evaluation. Although laparoscopic management of ICDF may be technically feasible, it is associated with a high conversion rate. Preoperative nutritional optimization may be beneficial in improving surgical outcomes in this select group of patients.

Short-term anti-TNF therapy with surgical closure versus anti-TNF therapy in the treatment of perianal fistulas in Crohn's disease (PISA-II): a patient preference randomised trial

Guidelines on Crohn's perianal fistulas recommend anti-tumour necrosis factor (TNF) treatment and suggest considering surgical closure for patients with surgically amenable disease. However, long-term outcomes following these two strategies have not been directly compared. The aim of this study was to assess radiological healing in patients who received short-term anti-TNF treatment and surgical closure compared with those who received anti-TNF treatment alone. The PISA-II trial was a multicentre, patient preference study done in nine hospitals in the Netherlands and one hospital in Italy. Adult patients with Crohn's disease and an active high perianal fistula with a single internal opening were eligible for inclusion. After counselling, patients with no treatment preference were randomly assigned (1:1) using random block randomisation (block sizes of six without statification), to 4-month anti-TNF therapy and surgical closure or anti-TNF therapy for 1 year, after seton insertion. Patients with a treatment preference received their preferred therapy. The primary outcome was radiological healing assessed by MRI at 18 months, defined as a complete fibrotic tract or a MAGNIFI-CD (Magnetic Resonance Index for Fistula Imaging in Crohn's Disease) score of 0, assessed according to the intention-to-treat principle. Secondary outcomes included clinical closure, number of patients undergoing surgical reintervention and number of reinterventions, recurrences, and impact on quality of life measured by the Perianal Disease Activity Index (PDAI). Analyses were performed on an intention-to-treat basis and additionally an as-treated analysis for radiological healing and clinical closure. This study was registered at the Dutch Trial Registry, NL7625, and with EudraCT, 2018-002064-15, and is closed to accrual due to completion. Between Sept 14, 2013, and Dec 7, 2019, 94 patients were enrolled onto the trial, of whom 32 (34%) were randomly assigned and 62 (66%) chose a specific treatment. 38 (40%) patients were assigned to the surgical closure group and 56 (60%) patients to the anti-TNF group. At 18 months, radiological healing was significantly more common in the surgical closure group (12 [32%] patients) than in the anti-TNF group (five [9%] patients; p=0·005). By contrast, clinical closure was not significantly different between the two treatment groups (26 [68%] patients in the surgical closure group vs 29 [52%] patients in the anti-TNF group; p=0·076). Significantly fewer patients required a reintervention in the surgical closure group than in the anti-TNF therapy group (five [13%] patients in the surgical closure group, median one reintervention [IQR one to three] vs 24 [43%] patients in the anti-TNF group, median two reinterventions [one to two]; p=0·005). Among patients who reached clinical closure during follow-up, four (14%) of 29 in the surgical closure group and five (16%) of 31 in the anti-TNF therapy group had a recurrence, which occurred only in patients without radiological healing. PDAI was significantly lower in the surgical closure group than in the anti-TNF group after 18 months (p=0·031). Adverse events and serious adverse events were similar in both treatment groups and mostly entailed reinterventions. Ten (11%) patients had side-effects associated with anti-TNF treatment. Two serious adverse events unrelated to study treatment occurred (appendicitis and myocardial infarction). One patient died from a tongue base carcinoma, unrelated to study treatment. Short-term anti-TNF treatment combined with surgical closure induces long-term MRI healing more frequently than anti-TNF therapy in patients with Crohn's perianal fistulas. These data suggest that patients with Crohn's perianal fistula amenable for surgical closure should be counselled for this therapeutic approach. Netherlands Organisation for Health Research and Development and Broad Medical Research Program.

Endoscopic Treatment of Enterocutaneous Fistulas in Crohn's Disease.

Management of enterocutaneous fistulas in Crohn's disease is challenging. Most patients still need intestinal resection in the biologic era. The aim of this study was to evaluate the efficacy of endoscopic treatment for enterocutaneous fistulas. This is a retrospective study of medical records. This study was conducted in a single institution. All consecutive patients with Crohn's disease with an enterocutaneous fistula who underwent endoscopic fistula closure with the use of an over-the-scope clip or a hemostatic clip were included. The main outcome measured was the clinical success 3 months after the procedure, which was defined as the complete closure of all fistulas at physical examination and complete cessation of the drainage from the external opening, without surgery. Eight patients (men, 25%; median age 45 years [interquartile range, 33-51]) were followed. Fistulas were localized at the ileocolonic or colocolonic anastomosis in 7 patients and at the stomach in 1 patient. Seven patients were treated with an over-the-scope clip, and one was treated with a hemostatic clip. Technical success was achieved in all cases. Clinical success at 3 months was achieved in 75% of cases (6/8 patients). After a median 16-month (interquartile range, 13-23) follow-up, 3 of 8 (37.5%) patients had enterocutaneous fistula closure and 2 of 8 (25%) needed intestinal resection. No complications were observed. The retrospective nature, the small sample size of the study, and the heterogeneity of the population limit the interpretation of the results. Endoscopic treatment of enterocutaneous fistulas is feasible with a short-term effectiveness. Additional studies are needed to confirm these results. See Video Abstract at http://links.lww.com/DCR/B614. ANTECEDENTES:Es desafiante el manejo de las fístulas enterocutáneas en enfermedad de Crohn. En la era biológica, la mayoría de los pacientes todavía requieren de resección intestinal.OBJETIVO:Evaluar la eficacia por tratamiento endoscópico de fístulas enterocutáneas.ENTORNO CLINICO:Estudio retrospectivo de registros médicos.AJUSTE:Realizado en una sola institución.PACIENTES:Se incluyeron todos los pacientes consecutivos con fístula enterocutánea en enfermedad de Crohn, sometidos a cierre endoscópico de la fístula con clip sobre el endoscopio o clip hemostático.PRINCIPALES MEDIDAS DE VALORACION:El éxito clínico a los 3 meses después del procedimiento. Definido al examen físico, como el cierre completo de todas las fístulas y cese completo del drenaje por la abertura externa, sin cirugía.RESULTADOS:Se estudiaron a ocho pacientes (hombres, 25%, mediana de edad de 45 años (rango intercuartílico, 33-51)). En 7 pacientes, las fístulas se localizaron en la anastomosis ileocolónica o colocolónica y un paciente, en el estómago. Siete pacientes fueron tratados con clip sobre el endoscopio y uno con clip hemostático. Se logró éxito técnico en todos los casos. Se logró éxito clínico a los 3 meses en 75% de los casos (6/8 pacientes). Después de una mediana de 16 meses (rango intercuartílico, 13-23), de seguimiento 3/8 (37,5%) pacientes presentaron cierre de fístulas enterocutáneas y 2/8 (25%) requirieron resección intestinal. No se observaron complicaciones.LIMITACIONES:Estudio retrospectivo, pequeño tamaño de la muestra y heterogeneidad de la población, limitaron la interpretación de los resultados.CONCLUSIONES:Es posible el tratamiento endoscópico de fístulas enterocutáneas con efectividad a corto plazo. Se requieren nuevos estudios para confirmar estos resultados. Consulte Video Resumen en http://links.lww.com/DCR/B614. (Traducción-Dr. Fidel Ruiz Healy).

Safety and Efficacy of Mesenchymal Stromal Cells and Other Cellular Therapeutics in Rheumatic Diseases in 2022: A Review of What We Know So Far.

Although a number of new immunosuppressive agents and biologics have been approved for treating various autoimmune inflammatory rheumatic diseases, there remains a substantial number of patients who have no clinical response or limited clinical response to these available treatments. Use of cellular therapies is a novel approach for the treatment of autoimmune inflammatory rheumatic diseases, with perhaps enhanced efficacy and less toxicity than current therapies. Autologous hematopoietic stem cell transplants were the first foray into cellular therapies, with proven efficacy in scleroderma and multiple sclerosis. Newer, yet unproven, cellular therapies include allogeneic mesenchymal stromal cells, which have been shown to be effective in graft-versus-host disease and in healing Crohn's fistulas. Chimeric antigen receptor T cells are effective in various malignancies, with possible application in rheumatic diseases, as shown in preclinical studies in murine lupus and recently in human lupus. Treg cells are one of the master controllers of the immune response and are decreased in number and/or effectiveness in specific autoimmune diseases. Expansion of autologous Treg cells is an attractive approach to controlling autoimmunity. There are a number of other regulatory cells in the immune system, including Breg cells, dendritic cells, macrophages, and other T cell types, that are in early stages of development as treatments. In this review, the current evidence for the efficacy and mechanisms of actions of cellular therapies already in use or in clinical trials in human autoimmune diseases will be discussed, including the limitations of these therapies and potential side effects.

Relationship between clinical remission of perianal fistulas in Crohn's disease and serum adalimumab concentrations: A multi-center cross-sectional study.

BACKGROUNDCrohn’s disease (CD) is complicated by perianal fistulas in approximately 20% of patients. Achieving permanent fistula closure remains a challenge for physicians. An association between serum anti-tumor necrosis factor-α concentrations and clinical outcomes in patients with CD has been demonstrated; however, little information is available on serum adalimumab (ADA) concentrations and remission of perianal fistulas in such patients.AIMTo study the relationship between serum ADA concentrations and clinical remission of CD-associated perianal fistulas.METHODSThis cross-sectional study of patients with CD-associated perianal fistulas treated with ADA was performed at four French hospitals between December 2013 and March 2018. At the time of each serum ADA concentration measurement, we collected information about the patients and their fistulas. The primary study endpoint was clinical remission of fistulas defined as the absence of drainage (in accordance with Present’s criteria), with a PDAI ≤ 4, absence of a seton and assessment of the overall evaluation as favorable by the proctologist at the relevant center. We also assessed fistula healing [defined as being in clinical and radiological (magnetic resonance imaging, MRI) remission] and adverse events.RESULTSThe study cohort comprised 34 patients who underwent 56 evaluations (patients had between one and four evaluations). Fifteen patients had clinical remissions (44%), four of whom had healed fistulas on MRI. Serum ADA concentrations were significantly higher at evaluations in which clinical remission was identified than at evaluations in which it was not [14 (10-16) vs 10 (2-15) μg/mL, P = 0.01]. Serum ADA concentrations were comparable at the times of evaluation of patients with and without healed fistulas [11 (7-14) vs 10 (4-16) μg/mL, P = 0.69]. The adverse event rate did not differ between different serum ADA concentrations.CONCLUSIONWe found a significant association between high serum ADA concentrations and clinical remission of CD-associated perianal fistulas.

Shape memory polymer hydrogels with cell-responsive degradation mechanisms for Crohn's fistula closure.

Crohn's disease, a form of inflammatory bowel disease, commonly results in fistulas, tunneling wounds between portions of the urinary, reproductive, and/or digestive systems. These tunneling wounds cause pain, infection, and abscess formation. Of Crohn's patients with fistula formation, 83% undergo surgical intervention to either drain or bypass the fistula openings, and ~23% of these patients ultimately require bowel resections. Current treatment options, such as setons, fibrin glues, and bioprosthetic plugs, are prone to infection, dislodging, and/or require a secondary removal surgery. Thus, there is a need for fistula filling material that can be easily and stably implanted and then degraded during fistula healing to eliminate the need for removal. Here, the development of a shape memory polymer hydrogel foam containing polyvinyl alcohol (PVA) and cornstarch (CS) with a disulfide polyurethane crosslinker is presented. These materials undergo controlled degradation by amylase, which is present in the digestive tract, and by reducing thiol species such as glutathione/dithiothreitol. Increasing CS content and using lower molecular weight PVA can be used to increase the degradation rate of the materials while maintaining shape memory properties that could be utilized for easy implantation. This material platform is based on low-cost and easily accessible components and provides a biomaterial scaffold with cell-responsive degradation mechanisms for future potential use in Crohn's fistula treatment.

The clover sign: an ileo-ileal fistula in Crohn's disease.

The clover sign: an ileo-ileal fistula in Crohn's disease.

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.

Increasing experience with the LIFT procedure in Crohn's disease patients with complex anal fistula.

Surgical management of anal fistulas in Crohn's disease (CD) is associated with high failure rates, and treatment options are limited due to ongoing proctitis, multiple tracts, and concern for incontinence and non-healing wounds. The aim of this study was to investigate the healing rate of ligation of the inters-sphincteric fistula tract (LIFT) for anal fistulas in Crohn's disease and identify prognostic factors for healing. This prospective analysis compared long-term healing rates of CD patients undergoing LIFT for anal fistulas. Consecutive patients with CD who underwent LIFT procedure at our institution, in the period from March 2012 to September 2019 were included. The main outcome was anal fistula healing rate. The study cohort of 46 patients (mean age of 34.2 ± 13.0years, 18 (40%) males). After a mean follow-up time of 33 ± 28months, fistula healing was seen in 30 (65%) patients. A total of 8 patients were noted to have inter-sphincteric recurrence and 8 patients had trans-sphincteric recurrence. Smoking at the time of surgery was significantly associated with LIFT failure (HR 3.18, 95% CI 1.18-8.61, p = 0.02). Other factors, such as age, sex, race, disease duration and location, type of fistula history of proctitis, preoperatively use of biologics or a seton, and previous repair attempts, did not appear to influence LIFT healing. Although not statistically significant, there was a trend toward increase in failure among patients with active proctitis at the time of surgery (HR 1.97, 95% CI 0.71-5.42, p = 0.19). Our increasing experience with LIFT for anal fistula in CD demonstrates a higher rate of healing (65%) than previously reported (48%). Smoking appears to negatively influence healing of LIFT in CD.

Mesenchymal Stromal Cell Therapy Improves Refractory Perianal Fistula in Crohn's Disease: Case Series Clinical Interventional Study.

Objective Perianal fistulas in Crohn’s disease (CD) are the main challenges in inflammatory bowel diseases (IBDs). Some of the fistulas are refractory to any therapeutic strategy. The aim of this study was to evaluate the therapeutic effects of mesenchymal stromal cells (MSCs) as a novel promising modality for the treatment of fistulizing CD. Materials and Methods This case series clinical interventional study was conducted from 2014 to 2017 at Shariati Hospital, an IBD referral center in Tehran, Iran. Refractory adult patients with CD who had draining perianal fistulas were enrolled in this study. All patients were examined by a colorectal surgeon and the fistula imaging studies were performed by pelvic magnetic resonance imaging (MRI). After autologous bone marrow (BM) aspiration and MSCs isolation, the cells were cultured and passaged under current good manufacturing practice (cGMP) conditions. Four intra-fistula injections of cells, each containing 40×106 MSCs suspended in fibrin glue, were administered by an expert surgeon every 4 weeks. Procedure safety, feasibility and closure of the perianal fistulas at week 24 were assessed. Clinical examination and MRI findings were considered as the primary end points. Results In total, 5 patients (2 males and 3 females) were enrolled in this study. No adverse events were observed during the six-month follow-up in these patients. Both the Crohn’s Disease Activity Index (CDAI) and Perianal Disease Activity Index (PDAI) scores decreased in all patients after cell injections and one patient achieved complete remission with closure of fistulas, discontinuation of fistula discharge, and closure of the external opening. ConclusionLocal injection of MSCs combined with fibrin glue is potentially a safe and effective therapeutic approach for complex perianal fistulas in patients with CD.

Essential updates 2020/2021: Colorectal diseases (benign)-Current topics in the surgical and medical treatment of benign colorectal diseases.

The development of new drugs for inflammatory bowel disease (IBD) is remarkable, and treatment strategies using multiple agents and various techniques are required; however, the treatment strategy is likely to be complex. Therefore, appropriate evaluation of traditional surgical treatment strategies and accurate knowledge of the efficacy and limitations of novel treatments are required. Total infectious complications were found to be associated with the use of corticosteroids and anti‐tumor necrosis factor‐α agents, but not with immunomodulators, anti‐integrin agents, and 5‐aminosalicylic acid. Regarding surgical procedures for IBD, conceived anastomosis methods, including Kono‐S for Crohn's disease stenosis, are associated with better outcomes than conventional techniques. Autologous cell transplantation for Crohn's fistulae has been shown to have a favorable outcome. Diverticulitis is increasing and will be treated more frequently in the future. Risk factors for the incidence of diverticulitis and differences in pathogenesis according to right or left side diverticulitis have been reported. Antibiotic therapy may be omitted for uncomplicated diverticulitis. Moreover, regarding surgical procedures, both bowel resection and anastomosis are associated with favorable short‐term outcomes, higher stoma closure rate, and superior medical economy compared to Hartmann's procedure. Risk factors for recurrence after diverticulitis surgery may provide better postoperative follow‐up. In this review, we explore the current topics of colorectal benign diseases, focusing on IBD and diverticulitis, based on clinical trials and meta‐analyses from 2020‐2021. This review consolidates the available knowledge and improves the quality of surgical procedures and perioperative management for IBD and diverticulitis.

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.

P295 Proctitis during Crohn’s disease, would it be a factor in the sustainability of anoperineal fistulas?

Abstract Background Rectal involvement during Crohn’s disease (CD) was identified as a risk factor associated with poor therapeutic response of anoperineal fistulas (APF). The aim of our study was to evaluate the impact of rectal mucosal healing on the healing of APF during CD treated with anti-Tumour Necrosis Factor Alpha (anti-TNFα). Methods We conducted a monocentric retrospective study, including records of all patients followed for CD with APF treated with anti-TNFα over a 10-year period [2010 - 2020]. We collected clinical, biological, endoscopic and radiological data as well as the evolution of the patients on anti-TNFα. The therapeutic response was assessed clinically and radiologically by perineal MRI. Healing of the rectal mucosa was investigated by endoscopy with biopsies, and compared with that of the APF. Results A total of 38 patients were included, with a mean age equal to 42 years [26 - 73] and a M/F sex ratio equal to 0,4. Two patients (5,2%) had exclusively perineal involvement. APF was associated with luminal involvement in 94,7% of cases. Twenty-three patients (60,5%) had associated proctitis. APF were complex in 92,1% of cases, associated with a perineal abscess in 44,7% of cases and anorectal stricture in 7,9% of cases. All patients had received anti-TNFα after disappearance of perineal collections if initially present (Infliximab (92,1%), Adalimumab (7,9%)) combined with thiopurines in 97,4% of cases. After a mean follow-up of 40 months, the response of the APF to treatment was associated with healing of the rectal mucosa in 10 patients (43,5%), healing of the APF alone with persistence of proctitis was observed in 6 patients (26,1%), healing of the rectum with persistence of APF was described in only one patient (4,3%). The absence of rectal and anoperineal healing together was observed in 6 patients (26,1%). In a univariate study and using the chi-square test, there was no statistically significant relationship between rectal mucosal healing and APF healing after treatment with biotherapy with p = 0,069 [95% confidence interval]. Conclusion Our results suggest that healing of the rectal mucosa does not influence the natural history of anoperineal fistulas in Crohn’s disease. Larger scale studies are needed to confirm these results.

P356 Czech experience with treatment of Crohn′s disease perianal fistulas by allogenic mesenchymal stem cell

Abstract Background Perianal complex fistulas in Crohn′s disease (CD) are difficult to treat by both surgical and conservative methods. Administration of allogenic, adipose-derived mesenchymal stem cells (darvadstrocel) was studied in a prospective randomised trial (PRS) with a success rate of more than, 50%. The aim of our study was prospectively evaluate results of commercial treatment of perianal fistulas in CD patients by darvadstrocel in Czech Republic. Methods We prospectively followed, 42 consecutive patients treated commercially by darvadstrocel since August, 2019 till August, 2021. Perianal CD activity index (PDAI) was recorded for all patients as well as well as AGA clinical fistula assesment. Complete healing was considered as: no secretion from the external opening, no infiltration perianally, no pain; treatment failure: clear perianal secretion, painful infiltration and / or the need for surgery; partial response: anamnestic mild secretion from one external opening, infiltration around the fistula without pain and without the need for surgical intervention. Results 42 prospectively monitored patients (17M /, 25F), average age, 42 years (range;, 21–70 years) underwent darvastrodstrocel treatment in, 2 Czech mesenchymal stem cell therapy centers (39 pp in NH Hospital, 3 in ISCARE center). Patients suffered from intestinal CD for an average of, 15.6 years (3–34 years), perianal CD for, 8.9 years (2–23 years) and underwent an average of, 7.5(3–24) minor perianal surgeries before the treatment., 38% (16) of patients had anorectal stenosis at the time of the treatment. Patients were treated on average, 25 months (6–84) by stable immunosuppressive and/or biologic therapy. Locally, it was complex fistulas, mostly high trans-sphincteric with, 1–3 external openings (EO) (78.6%;, 33 pp had, 1 EO) and with, 1–2 internal openings (IO) (14.3%;, 6 pp had, 2 IO). Patients were monitored for an average of, 10.5 months (range;, 4–26 months). Complete healing occurred in, 76% patients (32), partial response in, 11.9% (5pp) and treatment failure was in, 5 patients (11.9%). PDAI before MSC surgery was on average, 9.7 (3–13), 3 months after surgery, 3.2 (0–13) and, 6 months after surgery, 2.6 (0–13) in patients who have healed or healed partially. Conclusion The treatment was more successful in real life than in PRS, which may be due to the relatively short follow-up period. Another reason for better outcome could be proper selection of patients with long term stable conservative treatment, which demonstrates stable CD. In our conditions, this treatment is similarly effective as eradication of the fistula using AF, but it can also be used in difficult conditions such as anorectal stenosis or chronic changes in the rectal mucosa.

P449 Autologous fat graft injection for the treatment of perianal fistulas in Crohn’s disease: A systematic review and single-arm meta-analysis

Abstract Background Perianal fistulas are a debilitating complication of Crohn’s disease. Long-term fistula healing rates remain poor with a need for effective novel therapies. Autologous fat graft injections are hypothesised to promote healing through the regenerative effects of mesenchymal stem cells; however, its efficacy remains unclear. We herein evaluated the efficacy of autologous fat graft injections for the treatment of Crohn’s perianal fistulas in a systematic review and meta-analysis. Methods A systematic review using the PRISMA Statement guidelines was performed. Database searches of MEDLINE, Embase, and PubMed, and grey literature searches were completed from January 1st, 2001, to August 2nd, 2021. Included publications evaluated fat graft injections for the treatment of Crohn’s perianal fistulas. Excluded studies assessed injection of in vitro expanded mesenchymal stem cells or anovaginal fistulas. Primary outcomes included rates of clinical healing, which was defined as the presence of non-draining fistula tract external openings, and closure, which was defined as complete closure of fistula tract external openings. The secondary outcome was pooled clinical healing or closure, assessed in a random effects meta-analysis across identified studies, excluding case reports. Results A total of 1,258 publications were identified, with 891 articles assessed for eligibility and 107 deemed relevant for paper review. Six studies met inclusion criteria for qualitative analysis, comprising four single-arm intervention trials and two case reports. A total of 51 patients received autologous fat graft injections for treatment of Crohn’s perianal fistulas, with follow-up ranging from 3 to 12 months. Variable techniques and filtration kits were used to acquire and process the harvested fat, with further differences in tract preparation, graft volume, and adjunctive surgical techniques. Two studies evaluated clinical healing (n = 20) which was achieved in 20% and 60% at 3 and 12 months, respectively. Four studies evaluated clinical closure (n = 31) which was achieved in 100%, 83%, and 100% at 3, 6, and 12 months, respectively. Clinical healing or closure was achieved in 74% in the pooled meta-analysis (95% confidence interval: 0.57, 0.85), with moderate heterogeneity between studies (I2 Statistic: 59%; Cochran’s Q test: P-value < 0.05). See Figure 1. Conclusion Autologous fat graft injections for the treatment of Crohn’s perianal fistulas shows promising results as a novel therapy in this systematic review and meta-analysis. Limited efficacy data showed clinical healing or closure as early as 3 months, with 74% achieving clinical success up to 12 months. Further assessment in controlled matched studies is needed.

P325 Performance of new MRI scores: the modified Van Assche Index and the MAGNIFI-CD in the evaluation of the response to anti-TNFα in anoperineal fistulas in Crohn’s disease

Abstract Background Despite considerable therapeutic advances over the last two decades in the management of Crohn’s disease(CD), complex anoperineal fistulas(APF) still constitute a real therapeutic challenge for the practitioner. Treatment is mainly medico-surgical, combining seton drainage and biotherapy. The ultimate goal is to obtain a deep remission, which combines clinical remission and a normal perineal MRI. Thus, several MRI scores have been proposed to assess the therapeutic response of APF to biotherapy. The aim of this study was to investigate the reliability of the new MRI scores: the modified Van Assche Index(mVAI) and the MAGNIFI-CD in the evaluation of the response of APF to anti-TNFα, by comparing them to the old version of the Van Assche Index(VAI). Methods We conducted a retrospective study, including all patients followed up for CD with APF treated with anti-TNFα over a, 10-year period [2010–2020]. Clinical, biological, morphological and evolutionary data were collected. VAI, mVAI and MAGNIFI-CD scores were calculated from data provided by perineal MRI: number, locations, extensions and lengths of fistulous tracts, characteristics of collections. Clinical response to anti-TNFα was assessed by proctological examination, at the end of which the patients were classified into two groups: • Responders(26): having a complete remission (closure of all initially productive fistulous orifices) or partial response (closure of more than, 50% of orifices) • Non-responders(12): closure of less than, 50% of the initially productive fistulous orifices A statistical study was carried out to compare the performance of the different scores in assessing the response to treatment by calculating the area under the ROC curve with a, 95% confidence interval. Results A total of, 38 patients were included. The mean age was, 42 years [26–73] and the sex-ratio M/F was, 0,4. All patients had received anti-TNFα after disappearance of perineal collections if initially present (Infliximab in, 35 cases(92,1%) and Adalimumab in, 3 cases(7,9%)) combined with thiopurines in, 97,4%. The average duration of anti-TNFα therapy was, 46 months [5–180] The means of the different scores were calculated in responders and non-responders before and after anti-TNFα treatment respectively: A decrease in all three scores was observed after anti-TNFα treatment in the responders, in contrast to the non-responders, thus confirming therapeutic failure. Furthermore, the AUROC of the VAI, mVAI and MAGNIFI-CD scores in the assessment of response to anti-TNFα in APF were, 0,925, 0,908 and, 0,869 respectively. Conclusion Our results suggest that the old version of the VAI, as well as the mVAI and MAGNIFI-CD, are reliable scores with comparable performance in the assessment of response to treatment in APF in CD.