Treatment Of Perianal Fistulas Research Articles

Comparison of the Efficacy of Laser and Hybrid Seton Methods in the Treatment of Perianal Fistula.

To compare the efficacy and postoperative complications of laser and hybrid seton methods in the treatment of perianal fistula (PF). A descriptive cross-sectional study. Place and Duration of the Study: Department of General Surgery, University of Health Sciences, Bursa Yuksek Ihtisas Training and Research Hospital, Bursa, Turkiye, from January 2021 to April 2022. A total of 76 patients, with 46 in the hybrid seton group and 30 in the laser group, were included in the study. Perianal fistula classification was based on preoperative magnetic resonance imaging. The Likert satisfaction scale was assessed for patient satisfaction and the Cleveland Clinic Florida Faecal Incontinence (CCF-FI) scoring system was used for incontinence. Treatment outcome was determined based on success rate and postoperative faecal incontinence. The mean age of the patients was 43 ± 13 years and 59 (78%) of them were male. Forty-seven (62%) patients had simple fistula. Acute and late complications were significantly higher in the hybrid seton group than in the laser group (p <0.001). According to the Likert satisfaction scale, the rate of unsatisfied patients was significantly higher in the laser group than in the hybrid seton group (p = 0.02). According to the CCF-FI scoring system, incontinence was significantly higher in the hybrid seton group than in the laser group (p = 0.01). Treatment failure was higher in the laser group (p = 0.03). The laser method has lower intraoperative / postoperative complications, but higher treatment failure and lower patient satisfaction compared to the hybrid seton method. Anal fistula, Fecal incontinence, Laser therapy, Outcome, Loose seton method.

Compare the surgical outcome of Fistulectomy and Mucoal advancement flap in perianal fistula.

Objective: To compare the fistulectomy with mucosal advancement flap in treatment of perianal fistula in terms of mean hospital stay, frequency of anal incontinence and wound healing time. Study Design: Randomized Control Trial. Setting: Surgical OPD, DHQ and Allied Hospital, Faisalabad. Period: 1st March 2019 to 28 February 2020. Methods: Conducted on 120 (60 in each group) patients with fistula in ano presenting. Sampling technique was Non probability consecutive sampling. All the Patient age ranges from 20-55 years of either gender having perianal fistula which are low lying fistulas and with single external opening are included in study. Patients having perianal abscess, pilonidal sinus, Inflammatory bowel disease (Crohn’s disease, Ulcerative colitis) or with history of tuberculosis, HIV disease, Complex high lying fistulas with multiple external openings are excluded. Results: In our study, group A underwent fistulectomy while on group B we perform mucosal advancement flap. About 56.67%(n=34) in Group A and 50%(n=30) in Group B were between 20-40 years of age while 43.33%(n=26) in Group A and 50%(n=30) in Group B were between 41-55 years of age, mean+SD was calculated as 38.78+9.07 years and 40.12+8.89 years respectively. According to gender division 86.67%(n=52) in Group A and 78.33%(n=47) in Group B were male while 13.33%(n=8) in Group A and 21.67%(n=13) in Group B were females, mean hospital stay was calculated as 93.93+4.56 hours in Group A and 107.95+4.66 hours in Group B, p value was calculated as 0.0001 showing a significant difference between the two groups. Comparison of anal incontinence in both groups was done showing that 13.33% (n=8) in Group A and 23.33%(n=14) in Group B had anal incontinence, p value was calculated as 0.15. At one month postoperative follow-up only 4 patient (6.7%) in group A showed complete wound healing while in group B 28 patients out of 60(46.6%)showed complete wound healing, P value was calculated as 0.00167 showing a significant difference while there is no significant difference in incidence of early post-operative complications. Conclusion: We concluded that hospital stay was significantly decreased in cases with fistulectomy when compared with MAF while there was no significant difference regarding anal incontinence in both groups.

Modern treatment of perianal fistulas following Crohn’s disease

Modern treatment of perianal fistulas following Crohn’s disease

A Comprehensive Case Study on the Successful Treatment of Perianal Fistula in a Four-Year-Old Male

This case study gives a thorough account of how a four-year-old boy who had been experiencing recurrent discomfort and perianal discharge for six months was diagnosed, treated, and then recovered. An MRI fistulogram revealed a transphincteric fistula with both the internal and exterior apertures placed at the 9 o'clock position, despite the absence of concomitant diseases and prior procedures. The treatment method used methylene blue infiltration to verify the internal aperture and then metal probe probing of the track. From the exterior to the internal opening, a partial fistulotomy was carried out, and the raw proximal track was treated with Kshara sutra. Surprisingly, the fistula was fully cured in just three months. This case study gives priceless information that could direct future treatments and serves as a testimonial to the efficiency of such a therapy method in controlling juvenile fistulas.

Cystoscope-guided trans-anal Fistula-tract Laser Closure (FiLaC) of late onset recurrent recto-urethral fistula post anorectal malformation repair: A case report

Management of persistent and recurrent rectourethral fistula after primary treatment of anorectal malformations (ARM) is challenging. Various surgical techniques have been proposed and until today there is no consensus on the optimal approach. We describe a case of late onset recurrent rectourethral fistula after neonatal ARM repair, treated with a minimally invasive cystoscope-guided trans-anal Fistula-tract Laser Closure (FiLaC). A male patient suffering from ARM, type recto-bulbar fistula, was treated with an anorectoplasty during the neonatal period. Post-operatively, no reoperations were needed and long term follow-up demonstrated good functional outcome. At the age of 19 years, the patient presented with complaints of anal urinary leakage during micturition. Voiding-cysto-urethrography and perineal Nuclear Magnetic Resonance (NMR) demonstrated a fistula tract between the bulbar urethra and the distal rectum. Given the lack of associated urinary tract infections or fecaluria and the absence of fecal or urinary incontinence in between micturition, we decided to perform a trans-luminal, non-surgical approach. By analogy with the minimally invasive laser treatment of peri-anal fistula in adults, we performed a trans-anal cystoscope-guided FiLaC. We observed a fast post-operative recovery with an excellent one-year follow-up, illustrated by the elimination of symptoms, absence of fistula opening on rectoscopy and disappearance of the fistula-tract continuity on voiding-cysto-urethrography. This case exemplifies the potential benefits of using minimally invasive FiLaC treatment for the management of recurrent and persistent recto-urethral fistula following primary treatment of ARM. Long term follow-up is awaited to confirm the value of FiLaC in this treatment setting.

Management of Perianal Crohn's Disease - AJG.

Perianal Crohn's disease affects 25-35% of Crohn's disease patients and has proven to be one of the most difficult complications of the disease to treat. Patients with perianal Crohn's disease have lower health related quality of life scores typically related to pain and fecal incontinence. Additionally, perianal Crohn's patients have higher rates of hospitalizations, surgeries and overall healthcare costs. A multidisciplinary approach is necessary for the successful management of Crohn's disease with perianal fistula. Medical management is required to treat the underlying immune dysregulation to heal the luminal inflammation as well as the inflammation within the fistula tracts. Current options for medical therapy include biologics, dual therapy with thiopurines, therapeutic drug monitoring and close follow-up. Surgical management is critical to drain abscesses prior to immunosuppressive therapy and place setons when appropriate. Once the patient's inflammatory burden is well managed, definitive surgical therapies including fistulotomies, advancement flaps and ligation of intersphincteric fistula tract procedures can be considered. Most recently, the use of stem cell therapy in the treatment of perianal fistula has given new hope to the cure of perianal fistula in Crohn's disease. This review will outline the most current data in the medical and surgical management of perianal Crohn's disease.

Treatment of perianal fistulas in Crohn’s disease - review of literature and current recommendations

Introduction: Crohn's disease is an idiopathic inflammatory disorder of unknown etiology, associated with genetic, immunological, and environmental factors. The incidence of this disease continues to rise in developed countries. In almost 25% of patients, perianal fistulas occur during the course of the disease, which are difficult to treat and significantly impair the patient's quality of life.&#x0D; Aim of the study: To summarize the current state of knowledge on the treatment of Crohn's disease with perianal fistulas, with a particular focus on biological therapies and stem cell treatments.&#x0D; Methods and Materials: A systemic review was conducted using PubMed, Google Scholar, and ScienceDirect databases and it was limited to studies published in last 5 years. The search strategy was based on following terms: "Crohn's disease", "perianal fistula", "biological treatment", and "inflammatory bowel disease".&#x0D; Results: In recent years, there has been intensive research into new treatment options for perianal fistulas in Crohn's disease. Infliximab remains the first-line therapy, best controlled by monitoring the drug concentration in the serum. Alternatively, other drugs such as ustekinumab and vedolizumab may be considered. The combination of biological and surgical treatment is a recognized standard of care and modern, minimally invasive techniques that preserve sphincters, such as the FiLaC™ laser procedure, are increasingly being used. A novel and very promising therapeutic approach is based on mesenchymal stem cells, which may offer hope for patients who do not improve with standard treatment.&#x0D; Conclusion: Perianal disease in patients with Crohn's disease poses a significant therapeutic challenge and has a substantial negative impact on the physical and emotional well-being of patients. Despite the existence of various therapeutic options, a certain percentage of patients still fails to achieve clinical remission. Further research into new therapies is necessary.

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.

Effektivität von Mukosa Muskel Flaps in der Behandlung von perianalen Fisteln bei Morbus Crohn und kryptoglandulären Fisteln – eine Langzeit-Follow-up-Studie

Surgical treatment of perianal fistulae originating from Crohn's Disease (CD) or cryptoglandular abscess (CGA) remains a challenge. Data on long-term healing rates are scarce. We aimed to evaluate the long-term success rate of mucosal advancement flap (MAF) operations. This single centre retrospective analysis was performed at a tertiary referral centre (Charité University Hospital Berlin, Campus Benjamin Franklin) between March 1, 2010 and March 31, 2020. Patients with complex perianal fistulae originating from CD or CGA treated with MAF were included. Long-time healing rates of MAF in CGA and CD were compared. Regression analysis was used to identify predictive factors for definitive healing. 83 patients (24 CD, 59 CGA,) were included. Median follow-up for CD was 5.4 and 1.9 years for CGA. Definitive healing of fistulae was achieved in 19 (79.2%) CD patients (p=0.682) and in 44 (74.6%) CGA patients. Healing time was significantly shorter in CGA than in CD (9.3 months [standard deviation: SD=11.3 months] vs. 30.9 months [SD=23.5 months]; p<0.001). Treatment with biologicals (hazard ratio: HR=0.18, 95%-confidence interval: 95%-CI=0.06-0.59, p=0.004) and diverting ileostomy (HR=0.29, 95%-CI=0.10-0.85, p=0.023) in CD were independent predictors for MAF success. Simultaneous medication with azathioprine in CD was an independent predictor for MAF failure (HR=3.20, 95%-CI=1.05-9.81, p=0.041). This study demonstrates that surgical therapy of perianal fistulae with MAF is successful in about 75% of patients overall. Patients with MC benefit from biologicals and a diverting ileostomy. Treatment with azathioprine had a negative impact on recurrence rates. Repeated MAF operations did not increase the risk of failure in subsequent operations.

Approaches in the treatment of perianal fistula in Crohn disease

AbstractPerianal fistula is a common complication of Crohn disease, and it is a great burden on the life and psychology of patients, but its treatment is still a difficult problem to face. In recent years, progress in the treatment of Crohn disease has progressed rapidly due to the advent of biological agents, but there has been a lack of research on perianal fistula in Crohn disease, and the direction of research has been scattered; therefore, the author reviews the traditional treatment of perianal fistula in Crohn disease in the context of the available literature and discusses emerging and potential therapeutic approaches.

Platelet-Rich stroma from Crohn’s disease patients for treatment of perianal fistula shows a higher myeloid cell profile compared to non-IBD controls

BackgroundNew cell-based therapies are under investigation to improve perianal fistulizing Crohn’s disease (pCD) healing. Autologous stromal vascular fraction combined with platelet-rich plasma (referred to as platelet-rich stroma [PRS]) is a new adipose-derived stromal therapy. The effect of Crohn’s disease (CD) on adipose tissue, and adipose-derived therapies, is largely unknown. We characterized the cellular composition of subcutaneous lipoaspirate and PRS of pCD patients and non-Inflammatory Bowel Disease (IBD) controls. MethodsConsecutive pCD patients (≥18 years) and non-IBD controls, who underwent liposuction for the purpose of autologous PRS therapy, were included (October 2020 and March 2021). Mechanically fractionated lipoaspirate and the combined PRS product were analyzed for cell surface marker expression using fluorescence-activated cell sorting analysis. ResultsTwenty-three patients (37.8 [IQR 30.7–45.0] years; 9 [39.1 %] male; 11CD patients) were included. Similar total number of cells were found in CD and non-IBD lipoaspirate (CD 8.23 ± 1.62*105 cells/mL versus non-IBD 12.20 ± 3.39*105). Presence of stromal cells, endothelial like cells, immune cells, T-cells, myeloid cells and M2/M1 macrophage ratio were similar in CD and non-IBD lipoaspirate. In PRS samples, more cells/mL were seen in CD patients (P = 0.030). Myeloid cells were more abundant in CD PRS samples (P = 0.007), and appeared to have a higher regulatory M2/M1 ratio. Interdonor variation was observed between lipoaspirate and PRS samples. ConclusionsThe composition of CD and non-IBD lipoaspirate were found to be similar and interdonor variation was observed. However, PRS from CD patients showed more myeloid cells with a regulatory phenotype. Crohn’s disease does not appear to alter the immunological composition of adipose-derived products.

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.

The Intersection of Human and Veterinary Medicine-A Possible Direction towards the Improvement of Cell Therapy Protocols in the Treatment of Perianal Fistulas.

The effective treatment of perianal fistulizing Crohn's disease is still a challenge. Local administration of mesenchymal stromal cells (MSCs) is becoming a part of accepted treatment options. However, as a fledgling technique, it still can be optimized. A new trend in translational research, which is in line with "One Health" approach, bases on exploiting parallels between naturally occurring diseases affecting humans and companion animals. Canine anal furunculosis (AF) has been indicated as condition analogous to human perianal Crohn's disease (pCD). This narrative review provides the first comprehensive comparative analysis of these two diseases based on the published data. The paper also outlines the molecular mechanisms of action of MSCs which are likely to have a role in modulating the perianal fistula niche in humans, and refers them to the current knowledge on the immunomodulatory properties of canine MSCs. Generally, the pathogenesis of both diseases shares main determinants such as the presence of genetic predispositions, dysregulation of immune response and the relation to intestine microbiota. However, we also identified many aspects which should be further specified, such as determining the frequency of true fistulas formation in AF patients, elucidating the role of TNF and Th17 pathway in the pathogenesis of AF, or clarifying the role of epithelial-to-mesenchymal transition phenomenon in the formation of canine fistulae. Nevertheless, the available data support the hypothesis that the results from testing cell therapies in dogs with anal furunculosis have a significant translational value in optimizing MSC transplants procedures in pCD patients.

Advancing standard techniques for treatment of perianal fistula; when tissue engineering meets seton

Tissue engineering is a promising field for treating various diseases using tissue-like structures generated through biomaterials, scaffolds, nanoparticles, biomolecules, and stem cells. This advanced method is considered one of the next-generation therapeutic techniques that may solve the therapeutic challenges in treating perianal fistula based on seton therapy. Remarkable advances in stem cell biology, genetics, biomaterials, fabrication technologies, and nanotechnology have provided the opportunity to implement this multidisciplinary approach to repair damaged tissue in the seton-based fistula treatment. In addition, tissue engineering provides us with nanostructured biomaterials to fabricate setons that can act as scaffolds, with modified mechanical and biological properties such as antibacterial and anti-inflammatory. This review focuses on the applications, advantages, and future perspectives of tissue engineering to enhance the seton placement techniques and present a novel therapeutic solution to treat perianal fistula. In addition, in vivo and in vitro studies about implementing tissue engineering in the treatment of perianal fistula are reported in this study. Also, it summarizes the surgical procedures for the treatment of fistula, including Ligation of the Intersphincteric Fistula Tract (LIFT), Fistula Laser Closure (FiLaC™), Over-The-Scope Clip System (OTSC), Video-assisted anal fistula treatment (VAAFT), Anal fistula plug (AFP), and Rectal advancement flap (RAF). Furthermore, the applications and properties of different setons including, cutting setons (Penrose drains, rubber band, polypropylene, and silk), non-cutting setons (loose, knot-free, Comfort, and Super Seton®), and chemical setons (Ksharasutra) are described. In the end, we present the challenges and future trends of implementing tissue engineering technology in the seton-based therapy for the treatment of perianal fistula. The applications of tissue engineering in seton-based fistula therapy. The scaffolds with controllable mechanical properties and degradation rate can have antibacterial, anti-inflammatory, and drug-releasing properties. Besides, the scaffolds can be incorporated or covered with stem cells to regenerate damaged tissues in the perianal fistula site.

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.

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.

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 &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.

Long term efficacy of Video-Assisted Anal Fistula Treatment (VAAFT) for complex fistula-in-ano: a single-centre Australian experience.

Video-Assisted Anal Fistula Treatment (VAAFT) is a novel minimally invasive & sphincter-saving technique for treating complex fistula-in-ano involving endoscopic assessment & treatment of perianal fistula. This retrospective, non-randomized, observational study is the first Australian study of VAAFT. It is also the longest study of VAAFT to-date. From January 2014 to September 2019, 59 patients with a complex anal fistula were identified via MRI & underwent VAAFT. Fourteen patients had undergone previous definitive surgery for anal fistula. Specialized Karl Storz video equipment (fistuloscope) was used in the procedure. The rigid fistuloscope was used to directly visualize the fistula tract/s & internal opening. Closure of the internal opening was then performed. The fistula tract/s were then treated via fulguration. The external opening was kept patent & dressed. Patients were then followed up for a mean 59.5months. 67.9% (n= 38) of patients achieved primary healing (needing nil further intervention) at a median of 13 weeks. 12.5% (n= 7) experienced healing followed by recurrence while 19.6% (n= 11) experienced non-healing. Of the recurrence/non-healing groups, 11/18 underwent repeat VAAFT with healing occurring in 10/11 patients at a median of 7 weeks. The mean operating time was 41.1min. There were no major complications & continence scores were not affected. Three patients were lost to follow up. VAAFT is both effective & safe for the treatment of complex fistula-in-ano. Its minimally invasive nature means that in the instance of recurrence or persistence, VAAFT can be repeated with minimal morbidity & reasonable likelihood of success.