Crohn's Perianal Fistulas Research Articles

Perianal fistulas in Crohn's disease (review)

Treatment of аnal fistulas as perianal manifestations of Crohn’s disease is an important task, the solution of which has not yet been found. First of all, this is due to debilitating symptoms that reduce the quality of life. Incorrect tactics in the treatment of this disease can lead to the development of anal incontinence, and in some cases to the removal of the rectum. The purpose of this review was to study the effectiveness of various surgical methods for the treatment of perianal fistulas, the features of their use in various types of fistulas, as well as to assess the impact of surgical treatment on the function of the anal sphincter. It was found that most of the described methods were used in a strictly selected limited group of patients and allowed only temporary elimination of the clinical manifestations of Crohn’s disease. Unsatisfactory results of treatment, especially in the late postoperative period, a small number of clinical observations in published scientific papers on the treatment of perianal manifestations of Crohn’s disease, as well as low reliability of the results, dictate the need for further studies involving more patients.

Surgical management of complex perianal fistula revisited in a systematic review: a critical view of available scientific evidence

BackgroundTreating complex perianal fistulas in Crohn’s disease patients remains a challenge. Classical surgical treatments for Crohn’s disease fistulas have been extrapolated from cryptoglandular fistulas treatment, which have different etiology, and this might interfere with its effectiveness, in addition, they increase fecal incontinence risk. Recently, new surgical techniques with support from biological approaches, like stem cells, have been developed to preserve the function of the sphincter. We have performed a systematic literature review to compare the results of these different techniques in the treatment of Crohn’s or Cryptoglandular fistula.MethodsPubMed, EMBASE, Database of s of Reviews of Effectiveness, Cochrane Central Register of Controlled Trials were searched systematically for relevant articles. We included randomized controlled trials and observational studies that referred to humans, were written in English, included adults 18+ years old, and were published during the 10-year period from 2/01/2010 to 2/29/2020. Evidence level was assigned as designated by the Scottish Intercollegiate Guidelines Network.ResultsOf the 577 citations screened, a total of 79 were ultimately included in our review. In Crohn’s disease patients, classical techniques such as primarily seton, Ligation of Intersphincteric Fistula Tracks, or lay open, healing rates were approximately 50–60%, while in cryptoglandular fistula were around, 70–80% for setons or flaps. In Crohn’s disease patients, new surgical techniques using derivatives of adipose tissue reported healing rates exceeding 70%, stem cells-treated patients achieved higher combined remission versus controls (56.3% vs 38.6%, p = 0.010), mesenchymal cells reported a healing rate of 80% at week 12. In patients with cryptoglandular fistulas, a healing rate of 70% using derivatives of adipose tissue or platelets was achieved, and a healing rate of 80% was achieved using laser technology. Fecal incontinence was improved after the use of autologous platelet growth factors and Nitinol Clips.ConclusionNew surgical techniques showed better healing rates in Crohn’s disease patients than classical techniques, which have better results in cryptoglandular fistula than in Crohn’s disease. Healing rates for complex cryptoglandular fistulas were similar between the classic and new techniques, being the new techniques less invasive; the incontinence rate improved with the current techniques.

Observational Burden of Illness Study in Patients With Crohn’s Disease With and Without Perianal Fistulas in the United States

This study compared disease burden, experiences, and health-related quality of life (HRQoL) between patients with Crohn's perianal fistulas (CPFs) and those with Crohn's disease (CD) without perianal fistulas (PFs; non-PF CD). This cross-sectional, observational study was conducted in 3 cohorts of US patients aged 18-89 years with self-reported, physician-diagnosed CD: (1) non-PF CD; (2) CPF without PF-related surgery; and (3) CPF with PF-related surgery. Data on medical and surgical interventions, CD-specific symptoms, HRQoL (assessed using the Short Inflammatory Bowel Disease and 5-dimension EuroQol questionnaires), and fecal incontinence (assessed using Revised Faecal Incontinence Scale and Fecal Incontinence Quality of Life questionnaires) were collected via a web-enabled questionnaire. In total, 403 patients with CD completed the questionnaire (non-PF CD, n= 300; CPF without surgery, n= 51; CPF with surgery, n= 52). A high symptom burden was seen across cohorts. More patients with CPF underwent ≥1 CD-related surgery and experienced ≥1 failure of CD-related surgery (79% and 20%) vs non-PF CD (53% and 9%; P < .001). Overall HRQoL outcomes were worse for patients with CPF vs non-PF CD, with significantly worse Short Inflammatory Bowel Disease and 5-dimension EuroQol questionnaire scores for those without PF-related surgery (P < .01). Across all cohorts, 58% of patients reported experiencing fecal incontinence, which had a greater negative impact (higher Revised Faecal Incontinence Scale scores; lower Fecal Incontinence Quality of Life scores) in patients with CPF vs non-PF CD. Patients with CPF experience substantial HRQoL burden, reflecting the impact of symptoms and medical/surgical interventions. These results may help to inform comprehensive care strategies to improve patient HRQoL.

Efficacy and safety of mesenchymal stem cells in the treatment of perianal fistulas in Crohn's disease: a meta-analysis of randomized controlled trials.

Local mesenchymal stem cell (MSC) therapy for perianal fistulas in Crohn's disease (CD) has yielded promising results, but it still remains controversial. In this study, we aimed to conduct a meta-analysis of randomized controlled trials (RCTs) to evaluate the efficacy and safety of MSC therapy for perianal CD (pCD). RCTs reporting MSC therapy for perianal fistulas in CD were searched and included. The effectiveness and safety data were analyzed using RevMan 5.3. A total of 7 RCTs were included in this meta-analysis. The analysis showed that patients receiving MSC therapy presented a higher healing rate (HR) of pCD than those in the control group (odds ratio (OR)=1.42; 95% confidence interval (CI) 1.18, 1.71; P=0.0002). Compared with placebo (saline solution), MSC therapy improved the HR of pCD (OR=1.85; 95% CI 1.32, 2.60; P=0.0004). MSC therapy showed significant long-term efficacy (OR=1.36; P=0.009; 95% CI 1.08, 1.71). When MRI was used to evaluate fistula healing, a pooled analysis showed that the MSC group achieved a higher HR than the control group (OR=1.95; 95% CI 1.33, 2.87; P=0.0007). Allogeneic MSC therapy was superior to the control treatment in improving HR (OR = 1.97; 95% CI 1.40, 2.75; P<0.001). Furthermore, no significant differences were observed between MSC therapy and placebo in terms of adverse events (AEs) (OR = 1.16; 95% CI 0.76, 1.76; P = 0.48). None of the AEs were judged to be related to MSC treatment. This meta-analysis of RCTs provided evidence that local MSC injection is safe and efficacious for perianal fistulas in CD. In addition, this treatment has favorable long-term efficacy and safety profiles.

Fistula Remission 8 Weeks after Induction of Biologics is an Independent Influencing Factor for Long-term Prognosis in Bio Naïve Patients with Crohn's Perianal Fistulas

Fistula Remission 8 Weeks after Induction of Biologics is an Independent Influencing Factor for Long-term Prognosis in Bio Naïve Patients with Crohn's Perianal Fistulas

Clinical characteristics and MRI-based phenotypes of perianal abscess formation in children with fistulizing Crohn's Disease.

The aim of this study was to explore potential correlation of the MR imaging features and clinical characteristics with formation of perianal abscess in children with Crohn's perianal fistulas (CPF). From 2010 to 2020, pediatric patients with CPF diagnosis on their first pelvic MRI were identified retrospectively. All patients were divided into two groups based on the presence or absence of perianal abscess. Baseline clinical and MRI characteristics were recorded for each patient. All the statistical calculations were performed using R (version 3.6.3). A total of 60 patients [F:M 17:43, median age 14 years (IQR 10-15), ranging 3-18 years] were included in this study. Forty-four abscesses were identified in 36/60 children (mean volume 3 ± 8.6 ml, median 0.3 ml). In 24/60 patients with perianal disease, no abscess was detected on the MRI. Ten patients (28%) showed perianal abscess on pelvic MRI at the initial diagnosis. The rate of active disease on colonoscopy (visible ulcerations/aphthous ulcers) was similar in both groups (95% vs. 94%). With regards to disease location, the majority of patients (40/60, 66.6%) in both groups had ileocolonic CD. All patients without abscess had a single perianal fistula (n = 24; 3 simple and 21 complex fistulae), however, patients with perianal abscess tended to have >1 fistulous tracts (n = 50 fistulas; all complex, 27 single, 10 double and 1 triple). Intersphincteric fistula was the most common fistula type in both groups (79% and 66%, p = 0.1). The total length of fistula (3.8 ± 1.7 vs. 2.8 ± 0.8 cm, p = 0.006) and presence of multiple external openings (n = 25 vs. 7, p = 0.019) were significantly higher in patients with abscesses, and fistula length >3.3 cm showed 80% specificity and 83% PPV for the presence of perianal abscess. Fistulas were symptomatic (pain, bleeding or drainage) at similar rates in both groups (68% and 70%, p = 0.1). Pediatric patients with CPF who develop perianal abscess have a distinct imaging phenotype defined by longer fistula length (>3.3 cm), multiple skin openings and multiple fistulous tracts (≥2) on MRI. Patients who have these features but does not have an abscess on imaging may merit more aggressive treatment (and close monitoring) to prevent the development of an abscess.

The Multidisciplinary Management of Perianal Fistulas in Crohn's Disease: A Systematic Review.

Perianal fistulas in Crohn's disease (CD) are often recurring and challenging to treat. This systematic review aimed to evaluate the medical, surgical, and combination treatment options and provide an overview of their efficacy. We performed this systematic review following the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. Our group searched PubMed, Medline, PubMed Central, Google Scholar, and ScienceDirect for articles within the last ten years using different terms and criteria mentioned in detail in the search strategy and eligibility criteria sections. Initially, 739 records were retrieved, out of which we excluded 731 records for various reasons, such as irrelevant titles and abstracts and low scores on quality assessment tools. The evidence for combination (surgical and medical) therapy is superior to that for medical and surgical treatments individually. In contrast, the studies on medical and surgical treatments individually reported varied evidence and efficacy for their respective options.

Management of perianal fistulas in Crohn's disease: a 2021 update of the French National Society of Coloproctology consensus.

Since our last publication of algorithms for the management of perianal fistulas in patients with Crohn's disease, researchers have proposed a treat to target strategy systematic combotherapy for anal lesions, and indications for stem cell injection. In the absence robust publications, the Société Nationale Française de Coloproctologie (French National Society of Coloproctology [SNFCP]) wished to establish a group consensus using the Delphi method. From October 2020 to January 2021, a scientific committee and panel of gastroenterologists and surgeons established answers which were submitted to the members of the SNFCP during a national conference in November 2020. Three questions were clarified and reformulated, and then submitted during a third and final round of consultation of members of the SNFCP. The target was defined as being the response obtained in every domain (symptoms, physical and radiological evaluation) which could be considered satisfactory, without the need to intensify therapeutic management. By consensus, the time required for clinical evaluation of the efficacy of treatment was 6months. A response on magnetic resonance imaging (MRI) should include the absence of a collection of 10mm or more in size at 6months, and a frank decrease or complete disappearance of hyperintensity in T1 and T2 sequences of the main tract at 12months. Systematic association of an immunosuppressant with tumor necrosis factor inhibitors did not reach the consensus level for adalimumab (50%), but just did for infliximab (70%). The majority of the respondents considered failure of one, or even two lines of different biotherapies to be potential indications for injection of stem cells. These findings reinforce the importance of composite targets including MRI evaluation, and underscore the need for precise timing of evaluation. Combotherapy is only recommended with infliximab. Injection of stem cells is a second- or third-line option.

Cytokine Mixtures Mimicking the Local Milieu in Patients with Inflammatory Bowel Disease Impact Phenotype and Function of Mesenchymal Stromal Cells.

Locally applied mesenchymal stromal cells (MSCs) have the capacity to promote the healing of perianal fistulas in Crohn’s disease (CD) and are under clinical development for the treatment of proctitis in ulcerative colitis (UC). Despite these clinical advances, the mechanism of action of local MSC therapy in inflammatory bowel disease (IBD) is largely unknown. We hypothesized that the local cytokine environment in IBD patients affects the immunomodulatory properties of MSCs. To evaluate this, 11 cytokines were analyzed in inflamed tissues obtained from CD and UC patients. Based on the identified cytokine profiles 4 distinct cytokine mixtures that mimic various inflammatory IBD environments were established. Next, MSCs were cultured in the presence of either of these 4 cytokine mixtures after which the expression of immunomodulatory and tissue regenerative molecules and the capacity of MSCs to modulate T-cell proliferation and dendritic cell (DC) differentiation were assessed. Our data show that MSCs respond, in a cytokine-specific manner, by upregulation of immunomodulatory and tissue regenerative molecules, including cyclooxygenase-2, indoleamine 2,3-dioxygenase, and transforming growth factor-β1. Functional studies indicate that MSCs exposed to a cytokine profile mimicking one of the 2 UC cytokine milieus were less effective in inhibition of DC differentiation. In conclusion, our data indicate that cytokine mixes mimicking the local cytokine milieus of inflamed UC colonic or CD fistulas tissues can differentially affect the immunomodulatory and tissue regenerative characteristics of MSCs. These data support the hypothesis that the local intestinal cytokine milieu serves as a critical factor in the efficacy of local MSC treatment.

EE215 Higher Work Impairment and Increased Healthcare Resource Utilization in Patients with Crohn's Perianal Fistula: Results from a Global Burden of Illness Study

Perianal fistulas (PF) are a common complication of Crohn’s disease (CD), and patients with Crohn’s perianal fistulas (CPF) often have a greater burden of illness than patients with CD without PF. This study assessed the impact of PF on work productivity and healthcare resource utilization (HCRU) in patients with CD with and without PF.

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.

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.

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.

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.

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 &amp;lt; 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.

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.

A new treatment option for complex perianal fistulas in Crohn's disease patients; introduction of darvadstrocel (allogeneic expanded adipose-derived mesenchymal stem cells) and its development in Japan

A new treatment option for complex perianal fistulas in Crohn's disease patients; introduction of darvadstrocel (allogeneic expanded adipose-derived mesenchymal stem cells) and its development in Japan

Long-Term Outcomes of Crohn's Perianal Fistulas Treatment: Short-Term Anti-Tnf Therapy with Surgical Closure Versus Anti-TNF Therapy (PISA-II) - A Patient Preference RCT

Long-Term Outcomes of Crohn's Perianal Fistulas Treatment: Short-Term Anti-Tnf Therapy with Surgical Closure Versus Anti-TNF Therapy (PISA-II) - A Patient Preference RCT

P036 Disparities in Diagnosis and Management of Patients with Crohn's Perianal Fistulas: Results of a US National Patient and Caregiver Survey.

Crohn's perianal fistulas (CPF) contribute to lowered quality of life for patients with Crohn's disease. Previous research has indicated potential racial and/or ethnic disparities in diagnosis and management of patients with CPF. This study aimed to expand on previous investigations in the management of patients with CPF to identify educational needs and explore potential disparities in care. To understand specific educational needs of US patients and caregivers of patients with CPF, a survey instrument was developed and fielded to patients and caregivers in September/October 2020. Subanalysis and inferential statistics were used to segment the patient/caregiver sample by race/ethnicity and determine potential areas of care disparities. Of 148 patient/caregiver responses analyzed, 28 were non-white (including American/Alaskan Native Indian, Black/African American, Hispanic/Latino, Native Hawaiian/Pacific Islander, and multiethnic); 12/28 were CPF patients and 16/28 were parents or caregivers of CPF patients. The reported mean age of the CPF patient was 32 years for non-whites and 35 for whites. Insurance coverage varied between groups, with non-whites mainly covered by Medicare/Medicaid (68% vs 32% whites), and whites mainly covered by private insurance (64% vs 25% non-whites). Non-white patient/caregivers reported a longer mean time between symptoms and diagnosis (2.08 yr) than white patients/caregivers (less than 1 yr). White patients/caregivers reported more (50%) current use of biologics than non-whites (36%); however, past use of biologics was near equal (51%) for whites and (50%) for non-whites. Of patients who had undergone surgical procedures (86.5%), non-whites had a lower number of different surgery types (1.64) than whites (2.31). The top two reported goals of treatment for both groups were decreasing pain and healing the fistula. Less non-white patients/caregivers agreed or strongly agreed they were satisfied with their current quality of care (39%) and access to care (57%) than white patients/caregivers (72% and 69%, respectively). Non-whites were more likely to disagree or strongly disagree that the main doctor who treats CPF is knowledgeable about their CPF and its treatments (25% vs 3% whites), and that they agree or strongly agree they know more about CPF than their doctor (21% vs 15% whites). Patients/caregivers (non-whites vs whites) perceived somewhat, very or extremely significant barriers to care to be inadequate community social services for CPF care (82% vs 79%), out-of-pocket costs of care (71% vs 84%), limited information to make difficult decisions for their CPF treatment (82% vs 86%), physical/emotional stress of managing their CPF (82% vs 79%), lack of access to specialist care (89% vs 88%) and lack of effective treatments (86% vs 89%). Only 50% of non-white patients/caregivers and 69% of white patients/caregivers agreed or strongly agreed that they know where to go to get CPF information. Disparities in diagnosis and management of CPF exist between non-white and white patients/caregivers, including length of time to diagnosis, perceptions of quality of care and barriers to treatment. Further research into disparities in the management of CPF is needed, as is CPF education for patients/caregivers and HCP education on managing CPF in minority populations.

In Silico Preliminary evaluation of Cx601 as new therapeutic approach in hospital clinical paths

Abstract Crohn's disease is a chronic inflammatory bowel disease characterized by transmural inflammation and fistula formation. Perianal fistulas are a common complication of Crohn's disease and are estimated to affect up to 28% of patients in the first two decades after diagnosis, particularly those with colonic disease and rectal involvement. Complex perianal fistulas in Crohn's disease are challenging to treat, severely impair patients' quality of life and cause substantial morbidity. Allogeneic, expanded, adipose-derived stem cells (Cx601) are a promising new therapeutic approach, although their high cost is often discouraging. We aimed at assessing the safety and efficacy of this treatment in patients with complex perianal fistulas in patients with Crohn's disease. Therefore, we conducted a meta-analysis in order to evaluate this new therapeutic approach before introducing it as standard of care. We examined 8 studies published in the last 10 years, 5 of which were selected for the final analysis. The primary outcome assessed was the combined fistula remission (clinical + imaging) assessed through the clinical examination and MRI, the control being the traditional medical strategies (ie, antibiotics, immunomodulators and anti-tumour necrosis factor agents). We registered a total of 128 events (lack of remission) in the control group vs 94 in the experimental one (Confidence Interval for OR of 0,12-0,31, P &amp;lt; 0,001). Our “in silico” assessment is reliable, being the introduction of (Cx601) an innovative and effective treatment. Further insights will be provided by the INSPIRE registry, a multinational post-marketing study whose main objective is the evaluation of the real-world clinical effectiveness and safety of (Cx601) in patients affected by Crohn's disease with complex perianal fistulas for a duration of 36 months, to which our University “Federico II” is actively taking part. Key messages Disability reduction is an important goal in cronh therapeutic path of care. Our “in silico” assessment may support the introduction of (Cx601) an innovative and effective treatment.