Seton Drainage Research Articles

Long-Term Outcome of Surgery for Perianal Crohn's Fistula.

Background and Objectives: Patients with perianal Crohn's (CD) fistula often need repetitive surgeries and none of the established techniques was shown to be superior or preferable. Furthermore, the long-term outcome of fistula Seton drainage is not well described. The aims of this study were to analyze the long-term healing and recurrence rate of CD perianal fistulas in a large patient cohort. Materials and Methods: Database analysis of the Swiss IBD (Inflammatory Bowel Disease) cohort study. Results: 365 perianal fistula patients with 576 surgical interventions and a median follow-up of 7.5 years (0-12.6) were analyzed. 39.7% of patients required more than one procedure. The first surgical interventions were fistulectomies ± mucosal sliding flap (59.2%), Seton drainage (29.6%), fistula plugs or fibrin glue installations (2.5%) and combined procedures (8.8%). Fistulectomy patients required no more surgery in 69%, one additional surgery in 25% and more than one additional surgery in 6%, with closure rates at 7.5 years follow-up of 77.1%, 74.1% and 66.7%, respectively. In patients with Seton drainage as index surgery, 52% required no more surgery, and over 75% achieved fistula closure after 10 years. Conclusions: First-line fistulectomies, when feasible, achieved the highest healing rates, but one-third of patients required additional surgeries, and one-fourth of patients will remain with a fistula at 10 years. Initial Seton drainage and concurrent medical therapy can achieve fistula closure in 75%. However, in 50% of patients, more surgeries are needed, and fistula closure is achieved in only two-thirds of patients.

Salvage surgery for pouch-related complication after ileal pouch–anal anastomosis: a report of two cases

BackgroundPouch-related complications (PRCs), such as pelvic abscesses and perianal complex fistulas, can occur after ileal pouch–anal anastomosis (IPAA) in ulcerative colitis (UC). They are often difficult to treat and require salvage surgery. We report two cases of PRC associated with fistulas.Case presentationFirst case: A 38-year-old man was diagnosed with UC at age 26 years. Four months after the diagnosis of UC, the patient underwent hand-assisted laparoscopic restorative proctocolectomy, IPAA, and ileostomy for acute fulminant UC. Two years after the closure of the ileostomy, the patient developed a perianal abscess and underwent ileostomy reconstruction. He was referred to our department at 35 years of age, because his symptoms did not improve despite repeated seton drainage of a complicated perineal fistula. We diagnosed PRC with a pelvic abscess and complicated pouch fistula and performed salvage surgery. This diagnosis was revised to Crohn’s disease. Second case: A 50-year-old man was diagnosed with UC at age 18 years and was administered high doses of steroids; however, his symptoms did not improve. He underwent restorative proctocolectomy, IPAA, and ileostomy at another hospital. The ileostomy was closed, and his condition stabilized thereafter. At 35 years of age, perianal pain developed, and he was diagnosed with a complicated pouch–perineal fistula. A fistula was observed near the staple line of the ileal end closure on the head side of the pouch. Reconstruction of the ileostomy and seton drainage were performed; however, his symptoms did not improve, and he was referred to our hospital. We diagnosed PRC with a pelvic abscess and a complicated pouch fistula and performed salvage surgery. The resected specimen showed strictures in two locations: at the oral site of the afferent limb (at the pouch) and at the IPAA. Both patients returned to society and are currently outpatients.ConclusionsWe encountered two cases of PRC after IPAA that did not improve with seton drainage or ileostomy. Pouch resection was performed after considering the patient’s quality of life and reintegration into society.

Perianal Fistula; from Etiology to Treatment - A Review.

Anal fistula has been a challenging clinical issue for years due to its complex pathogenesis. The risk of frequent recurrence and incontinence complicates long-term treatment. Recent scientific literature has reviewed new techniques used for anal fistula treatment in recent years, assessing the advantages and disadvantages of each based on clinical outcomes. Although surgery is the main method used to treat anal fistula, there is no simple technique that can completely heal complex anal fistula. The surgical treatment should consider the healing outcome and the protection of anal function comprehensively. Several innovative techniques have emerged in recent years, such as combined techniques based on drainage seton and LIFT-plug, which appear to be relatively effective therapies. However, more multi-center prospective trials with long-term follow-up are needed to validate their effectiveness. In some situations, medical treatment may also be considered.

P857 Effectiveness and safety of subcutaneous infliximab in perianal Crohn's disease: a multicentre cohort study

Abstract Background Infliximab (IFX) demonstrated its effectiveness in perianal CD (pCD) and represents the first-line medical treatment. A subcutaneous (SC) formulation has recently been developed, however so far it has not been specifically investigated in pCD. The aim of our study was to evaluate the effectiveness and safety of SC IFX in pCD. Methods We conducted a multicentre retrospective cohort study in the French GETAID, in patients with either active (group 1) or inactive (group 2) pCD who received SC IFX. Inclusion criteria were, for group 1: active pCD in the 6 months prior to initiation of SC IFX; and for group 2: inactive pCD for > 6 months at the time of IV to SC switch, but with a history of seton drainage. The primary endpoint in group 1 was clinical remission at 6 months (absence of anal ulcers, and absence of draining fistula). Univariate and multivariable logistic regression analyses were performed to identify predictors of clinical remission. In group 2, the primary endpoint was perianal clinical recurrence during follow-up. Results A total of 192 patients were included in 24 centres. Mean age was 38.9 years, 43.2% were women, 25.1% were smokers. 66 patients were included in group 1, 117 in group 2. In 9 patients, pCD had a > 6 months persistent activity on IV IFX when switched to SC. In group 1, median follow-up was 46 (26.6-64.6) weeks, 51/66(77.3%) patients received combination therapy, surgical drainage was performed in 40(60.6%) patients. One(1.5%), 1(1.5%), 32(48.5%), 20(30.3%) and 12(18.2%) patients received 0, 1, 2, 3 and ≥ 4 IV perfusions respectively before SC switch. At M6, 27/61(44.3%) patients were in clinical remission and 53/61(86.9%) in clinical response. MRI remission or response was achieved in 19/28(68%) patients. In univariate analysis, factors inversely associated with remission were BMI, previous pCD surgery, initial seton drainage, and SC dose optimization. In multivariable analysis, prior exposure to ≥1 biologic (OR 0.248;CI95% [0.071-0.861]p= 0.0243) was predictive of clinical remission. In group 2, median follow-up was 53.6(36.7-67) weeks. The pCD recurrence rate at 6 months was 3.1%. The recurrence-free survival curve is shown in Figure1. Overall, SC IFX was discontinued in 20(10.4%) patients, 8 switched back to IV. Two cases of immunization were observed. Median IFX serum concentration was > 20(17.1- > 20) µg/l. There were 16(8.3%) cases of adverse events related to pain/injection-site reaction: 4 switched back to IV, 1 stopped IFX. There were 5 cases of infection, no case of cancer. Conclusion Our results are in line with those reported in the literature on the effectiveness of IV IFX in pCD. The SC formulation appears to be effective and safe for active pCD, and for maintaining remission in inactive pCD

P541 Long-term follow-up results of darvadstrocel for complex perianal fistulas in patients with Crohn's disease: 3-year outcomes from a Japanese phase 3 study

Abstract Background Darvadstrocel (DVS), a suspension of expanded human allogeneic mesenchymal stem cells extracted from adipose tissue, is for the treatment of complex perianal fistulas in patients with Crohn's disease (CD). In Japan, DVS was approved in 2021 based on the Japanese phase 3 study Week 52 data combined with the pivotal study ADMIRE-CD data. Patients who participated in the Japanese study were monitored for 3 years, and we report the results at Week (W) 156. Methods This was an open-label, uncontrolled, phase 3 study (converted to a post-marketing clinical study after approval) conducted from March 2019 to February 2023 in Japan. Subjects had complex Crohn’s perianal fistulas (CPF) refractory to conventional treatments with a maximum of 2 internal openings (IO) and 3 external openings (EO). The fistula tract was curetted approximately 2-3 weeks before DVS administration, and a drainage seton was placed. On the day of administration, seton was removed, fistula tracts were curetted again, and IO was sutured. A total of 24 mL of DVS (including 120x106 cells) was administered around the IO and into the wall of fistula tracts. During the 2-year follow-up period after W52, medical and surgical treatment for CD and CPF was given as needed, and subjects were assessed every 6 months. Results 22 Japanese patients were enrolled from 9 sites. The mean (SD) age was 36.4 (10.4) years, 63.6% were male, and the mean (SD) duration of CD was 11.3 (6.6) years. By W156, most frequently reported adverse events (AE) were anal fistula (7/22), proctalgia (7/22), and nasopharyngitis (6/22). New serious AE occurred after W52 were found in 9 subjects: COVID-19 (4), CD (2), perianal fistula, small bowel obstruction, premature labour (1 each). None of these were considered DVS-related. At W156, the combined remission rate (clinical and MRI assessment) was 15/22 (68.2%, 95% CI [48.7%, 87.6%]), clinical remission rate (clinical assessment) was 15/22 (68.2%, 95% CI [48.7%, 87.6%]), response rate (no drainage from ≥50% of treated EOs) was 20/22 (90.9%, 95% CI [78.9%, 100.0%]), and relapse rate (at least 1 relapse by W156 after achieving remission at W52) was 3/15 (20.0%, 95% CI [0.0%, 40.2%]). Mean Perianal Disease Activity Index (PDAI) total score (SD) was 4.8 (2.2) at baseline, which was decreased to 2.1 (2.1) at W52, and 1.7 (2.0) at W156. Mean Crohn's Disease Activity Index (CDAI) total score (SD) was 94.3 (60.1) on the day of administration, which was decreased to 73.7 (73.6) at W52, and 71.4 (51.2) at W156. Conclusion This is the first prospectively observed clinical outcomes in CPF for 3 years after DVS administration. There were no new safety findings, and fistula remission observed at W52 was maintained until W156.

On fistulas and threads : Sense and nonsense of seton drainage

In the daily practice of alarge proctological center numerous wrong or misplaced fistula threads are encountered. This indicates that there are misconceptions and knowledge gaps in this surgical field in nonspecialized general surgeons. Comprehensive footage of own experiences in aproctological center shows faulty threads and correct loop placement. In fistula treatment there is still a distinct need for improvement. This synopsis is an educational contribution. In the case of alack of experience in proctological surgery, education and training has to be provided for the decent management of anal fistulas with correct threads.

Distalization of perianal fistulas after loose silicone seton drainage is a myth

BackgroundIt is often stated that loose seton drainage results in distal migration of a fistula tract in perianal fistula. The aim of the present study was to assess this distalization of trans- and suprasphincteric perianal fistulas after a silicone seton has been inserted.MethodsConsecutive patients who underwent loose seton placement for the management of a transsphincteric or suprasphincteric fistula between January 2016 and December 2021 with a pre- and postoperative magnetic resonance imaging (MRI) were included in the present retrospective study. The height of the external anal sphincter (EAS) and the level of penetration of perianal fistula through the EAS or puborectal muscle (PRM) were determined on MRI. Primary outcome was migration of the fistula tract through the EAS and PRM.ResultsThirty-eight patients with perianal fistulas were included. Median height of the EAS was 28 (IQR 25–34) mm before seton placement and 27 (IQR 24–33) mm afterward. Median level of perforation was 32 (IQR 17–40) mm before seton placement and 28 (IQR 17–40) mm afterward (p = 0.37). One fistula (3%) was downgraded from mid to low transsphincteric and was laid open after 14.9 months of loose seton drainage.ConclusionsNo statistically significant distalization of complex fistula tracts after loose silicone seton drainage was found. Some complex fistulas may downgrade to a less complex fistula after long-term seton drainage. However, loose silicone seton drainage should not be offered to patients as a treatment option to downgrade a complex fistula to a simple one or even have the hope to heal it.

Crohn’s disease-related anal fistula cancer diagnosed by examination under anesthesia: a case report

BackgroundAs the number of patients with inflammatory bowel disease (IBD) increases, the incidence of IBD-related colorectal cancer (CRC) is also on the rise. Crohn’s disease (CD)-related CRC has been reported to have a poorer prognosis than sporadic CRC, and the early detection of CD-related CRC is difficult. Japanese patients with CD are reported to have a higher frequency of anorectal cancer than the Western population; however, methods for early diagnosis have not yet been established because of perianal pain during the examination.Case presentationWe report a case of CD-related anal fistula cancer that was detected early by surveillance examination under anesthesia (EUA). The patient was a 37-year-old man, diagnosed with CD at the age of 15 years and started medical treatment. However, due to poor disease control, the intestinal tract remained highly inflamed and the patient continued to have over 10 bowel movements per day. He was referred to our hospital for surgical treatment after a colonoscopy (CS), which revealed multiple active ulcers and stenoses. Since three perianal seton drainage tubes had been placed around his anus since the age of 33 years, we decided to perform an EUA to rule out cancer coexistence in the anorectal region. After a random biopsy of the rectum by CS under general anesthesia, we resected and curetted multiple perianal fistulas as much as possible and reinserted the seton drainage tubes. Pathological examination of the fistula tract revealed adenocarcinoma in one tract, indicating the coexistence of anal fistula cancer. Based on the diagnosis of multiple intestinal stenoses and anal fistula cancer due to CD, we performed hand-assisted laparoscopic total colectomy, rectal amputation, extensive perineal resection, and reconstruction using a left rectus abdominis flap.ConclusionIn a long-term CD patient with anorectal lesions, we performed an EUA to diagnose the coexistence of anal fistula cancer at an early stage, and surgical resection was achieved. EUA is effective for the early detection and treatment of CD-related CRC and may contribute to an improved prognosis.

Current Therapy of Cryptoglandular Anal Fistula: Gold Standards and Alternative Methods.

Cryptoglandular anal fistulas are one of the most common colorectal diseases and occur with an incidence of about 20/100,000. Anal fistulas are defined as an inflammatory junction between the anal canal and the perianal skin. They develop from an abscess or chronic infection of the anorectum. Surgical treatment of the disease is the method of choice. Even when treating an acute abscess, its cause should be sought at the same time. If there is a connection to the anal canal without affecting relevant parts of the sphincter muscles, primary fistulotomy should be performed. If larger parts of the sphincter muscle are involved, the insertion of a seton drain is usually useful. There are essentially two recommendations for the elective treatment of cryptoglandular anal fistulas. Distal fistulas should be excised, with the proviso that as little sphincter muscle as possible is sacrificed. In the case of highly proximally located and complex fistulas, sphincter-preserving surgical techniques should be used. In this case, the method of choice is the mucosal or advancement flap. Alternatively, clips, fibrin injections, fistula plugs, fistula ligatures, or laser-based procedures are described in the literature. In the case of intermediate fistulas, a fistulectomy with primary sphincter reconstruction can be useful. Every operation is carried out as a compromise between definitive healing of the fistula and a potential risk to the patient's continence. It is often difficult to make a reliable prognosis about the continence function to be expected postoperatively. In addition to the fistula morphology, particular attention should be paid to whether previous proctological operations have already been performed, the gender of the patient, and whether there are pre-existing sphincter dysfunctions. Since the surgeon's expertise plays a decisive role in the success of the treatment, the procedure should be carried out in a specialist proctological centre, especially in the case of complex fistulas or in the case of a condition after previous operations. In addition to the classic procedures, such as fistulectomy or the plastic fistula closure, this article examines alternative methods and their areas of application.

Systematic Review of Endoscopic Management of Stricture, Fistula and Abscess in Inflammatory Bowel Disease

Background: Interventional inflammatory bowel disease (IIBD) therapies can play a key role in inflammatory bowel disease (IBD) related stricture/fistula/abscess deferring or avoiding invasive surgery. Methods: A total of 112 studies pertaining to IIBD therapy for strictures/fistula/abscess between 2002 and December 2022 were included by searching Pubmed, Medline and Embase with a focus on technical/clinical success, recurrence, re-intervention and complications. Results: IIBD therapy for strictures include endoscopic balloon dilation (EBD), endoscopic stricturotomy (ES) and self-expanding metal stent (SEMS) placement. EBD is the primary therapy for short strictures while ES and SEMS can be used for refractory strictures. ES has higher long-term efficacy than EBD. SEMS is inferior to EBD although it can be useful in long, refractory strictures. Fistula therapy includes endoscopic incision and drainage (perianal fistula)/endoscopic seton (simple, low fistula) and endoscopic ultrasound-guided drainage (pelvic abscess). Fistulotomy can be done for short, superficial, single tract, bowel-bowel fistula. Endoscopic injection of filling agents (fistula plug/glue/stem cell) is feasible although durability is unknown. Endoscopic closure therapies like over-the-scope clips (OTSC), suturing and SEMS should be avoided for de-novo/bowel to hollow organ fistulas. Conclusion: IIBD therapies have the potential to act as a bridge between medical and surgical therapy for properly selected IBD-related stricture/fistula/abscess although future controlled studies are warranted.

P556 Surgery in high-risk paediatric Crohn’s Disease treated with up-front anti-TNF agents and long-standing biologic therapy

Abstract Background High-risk (HR) Crohn’s Disease (CD) is associated with high surgical and progression rates. Therefore, recent ESPGHAN guidelines (GL) suggest starting an early anti-TNFα treatment to modify the natural history of the disease. The aim of our study was to evaluate the surgical rate in a population of HR-CD paediatric patients treated with up-front anti-TNFα agents and long-standing biologic therapy Methods This is a retrospective, observational, single-center study conducted at the Paediatric Gastroenterology, Hepatology, and Endoscopy Unit at Policlinico Umberto I Hospital – Sapienza University of Rome. We collected data from all patients diagnosed with CD under 18 years, with a minimum follow-up of 12 months. between June 2008 to July 2022. Patients were then stratified at the diagnosis into HR and LR, based on ESPGHAN GL criteria. Demographic, clinical, laboratory, endoscopic, and imaging data were collected at 6, 12, 24, 36, 48, and 60 months Results 130 patients were enrolled, 76 HR (58%) and 54 LR (42%) [median age 12.5 (IQR) yrs, female 45 (35%), medium follow-up 54±24 months]. The HR group included 39 patients (51%) with panenteric disease, 15 (20%) with a structuring behavior (B2), 3 (4%) with structuring/penetrating disease (B2-B3), and 26 (34%) with perianal involvement (p). Early anti-TNFα agents were started in 80% of patients <6 months from the diagnosis, while 15 (20%) started biological therapy between 6 and 12 months from the diagnosis. All patients continued biologic therapy throughout the study follow-up: 20 (26%) optimized anti-TNF, 25% switched biologic, 11% added an immunomodulator, and 4% combined 2 biological drugs. The surgical rate at 5 years was 29% (n=22) and 29% n=16) in HR and LR groups respectively (p-value 1,0). Eleven % (n=8) of HR patients needed surgical resection, while perianal surgery (seton drainage, fistulotomy, fistulectomy) was performed in 18% (n=14), with no significant difference with LR group [(intestinal resection 18% (10/55), perianal surgery 11% (6/55), p > 0.05]. Perianal disease resulted positively associated with surgical risk (p 0.002, OR 5.62 CI 1.84-17.15) while small bowel imaging at the diagnosis was a protective factor for surgery (p 0.017, OR 0.23 CI 0.07-0.77). No significant difference was found in the interval free from surgery between HR and LR, although HR children mainly needed surgery in the first 12 months after the diagnosis. Conclusion Our data suggest that paediatric patients with HR-CD treated with early anti-TNF agents and long-standing biologic therapy have a similar disease course and surgical risk to those with LR disease. At a 5-year follow-up, one-third of patients needed surgery, mainly in the first year after the diagnosis

P166 Calprotectin in patients with perianal fistula: the CANALS study

Abstract Background Previous studies suggest that faecal calprotectin can be used to discriminate Crohn’s disease (CD) perianal fistulas from cryptoglandular (CG) perianal fistulas. The aim of this research was to prospectively validate these findings and further investigate local calprotectin production inside fistula tracts. The aim of the current study was to prospectively analyse the clinical value of calprotectin levels in both the faeces and the fistula tract. Methods In this prospective study, all consecutive patients with an active perianal fistula undergoing examination under anesthetics were included. Faecal and scraping calprotectin levels collected during surgery were measured. The primary objective was to differentiate between active CD perianal fistulas and CG perianal fistulas based on faecal calprotectin. Secondary outcome parameters were the levels of local calprotectin in fistula tracts and the correlation with fistula characteristics and clinical prognostic parameters like the Geldof Classification system. Results Sixty-three fistula patients were included in this study (CD n=45; CG n=18). Faecal calprotectin values were significantly higher in CD patients compared to CG patients (396.8 [61.9-1136.8] vs. 47.3 [14.6-233.6] ug/g, p=0.004). The Area Under the Curve (AUC) was 0.733 (95% CI [0.644 to 0.903] with an optimal FC cut-off value of 344ug/g. Faecal calprotectin was not related to calprotectin levels in fistula scrapings which was not significantly different in CD and cryptoglandular fistulas (p=0.893). Calprotectin in fistula scrapings was also not related to fistula characteristics like number of tracts, duration of disease or (previous) seton drainage. However, a significant correlation was found between scraping calprotectin and fistula disease severity and prognosis as defined by a new Geldof classification system: Patients in group 2a (amenable for fistula repair) had significantly lower calprotectin levels (140 [31.0-149.0])ug/g) when compared to class 2b (symptom control) (706 [198.5 – 1936]ug/g, p=0.054) and class 2c (gradually debilitating disease) (3464.0 [328.5-5692.0]ug/g, p=0.008). Patients in class 3 (exhausted perineum) had the highest calprotectin levels highest (5928.0 [2605.0-6000]ug/g). Conclusion CD and CG perianal fistulas can be distinguished by measuring faecal calprotectin levels. The difference can not be explained by local fistula calprotectin production as calprotectin in fistula scrapings is not predictive of CD. However, the results of this study suggest that scraping calprotectin levels may be used to classify fistula patients and predict outcome of fistula treatment.

P603 Real-world Scottish experience of anti-TNF therapy in paediatric Crohn’s disease 2016-2020 against the ECCO-ESPGHAN recommendations

Abstract Background ECCO-ESPGHAN updated the guideline on the management of paediatric Crohn’s disease (CD) in 2021. This promoted a move to early risk stratification and a ‘top-down’ (anti-TNF within 4 weeks of diagnosis) approach for patients who were deemed high-risk. High-risk was defined by extensive panenteric or severe disease, perianal, stricturing and/or penetrating behaviour. We sought to compare the use of anti-TNF therapy against the new guidance by conducting a Scottish nationwide retrospective multi-centre study (all three regional PGHAN units). Methods We analysed a prospectively identified nationwide cohort of all new paediatric CD patients (<18 years) diagnosed in Scotland between 01/01/16 and 31/12/20. We retrospectively collected data from electronic medical records on the use of anti-TNF therapy (infliximab or adalimumab) within 18 months of diagnosis. Paris location and behaviour at diagnosis were determined, allowing us to split the patient group into high-risk or low/medium-risk as per latest ECCO-ESPGHAN guidance. Data regarding surgical intervention was collected and defined as: Perianal (Seton suture or drainage of abscess) and/or bowel resection +/- stoma formation. Results 419 patients were included (259/419 male; median age at diagnosis 13.2 yrs). Disease phenotype and behaviour are shown in tables 1 and 2. 225/419 (54%) were classified as high-risk and 194/419 (46%) as low/medium-risk. 171/225 (76%) high-risk and 78/194 (40%) low/medium-risk patients received anti-TNF within 18 months of diagnosis, with median start at 5 months (IQR: 1- 8 m) and 6.5 months (IQR: 3 – 13 m) respectively. Figure 1 demonstrates cumulative anti-TNF new starts by month. Of these patients, 49/171 (40%) high-risk and 12/78 (15.3%) low-risk received anti-TNF within 4 weeks of diagnosis. High-risk patients were more likely to receive anti-TNF (76.0% vs 40.2%, p<0.0001). 37 (8.8%) patients underwent surgical intervention; 31/225 (13.7%) high-risk and 6/194 (3.1%) low/medium-risk (13.7% vs 3.1%, p= 0.0002). Conclusion The ECCO-ESPGHAN guidance seeks to shift practice towards “top-down” anti-TNF therapy in high-risk patients. Our real-world data supports this view by showing that high-risk patients are more likely to require biologics within 18 months and more likely to require surgery than low/medium-risk patients. The ECCO-ESPGHAN approach would however have led to unnecessary anti-TNF in 24% of our high-risk cohort within 18 months of diagnosis. The financial cost and risk:benefit profile of this group should be considered carefully both in clinical practice and future guidance.

DOP76 Comparison of healing of complex perianal Crohn′s disease fistulas by advancement flap and mesenchymal stem cell therapy

Abstract Background The combination of surgical approach and biologic treatment is the most successful approach to achieve healing of perianal Crohn′s disease (CD) fistulas. Alongside conventional surgical methods (advancememt flap AF), a new method of fistula closure - allogeneic mesenchymal stem cell (MSC) therapy found its way to clinical practice. Methods The aim of a single centre prospective observational study was to compare the healing results of complex perianal CD fistulas by advancement flap and mesenchymal stem cell therapy (by darvadstrosel). 119 consecutive CD patients with complex fistula (95 with anorectal and 24 anovaginal); treated by MSC-darvastrocel in between 2018 to 3/2022. All patients had a long term loose seton drainage and optimized conventional therapy with luminal remission confirmed by colonoscopy. Complete healing was clinically assessed (no visible external opening or a scar without secretion, no inflammation, no subsequent perianal surgery needed within 3 months post index surgery). Results AF group: Duration of luminal CD was 8,84 years (1-38) and perianal CD 4,74 years (0,5-17). Patients underwent 4,22 (1-23) previous perianal surgeries. The follow up was 11,47 months (0,5-48,9). Conservative therapy (biologics and immunosuppressants) was stable for 23,1 months (1-137). Patients did not suffer from anorectal stenosis or rectal inflammation. MSC group: (60 pp. 36F/24M): Duration of luminal CD was 13 years (2-43 years), of perianal CD 7 years (2-23 years). Number of previous perianal surgeries was 8 (3-25). Conservative therapy was stable for 19 months (1-120). Follow up was 12,5 months (5-34). 38,3% (23) of patients had anorectal stenosis, 38,3% patients underwent advancement flap procedure prior, and 62% suffered from chronic inflammation in rectum. Complete healing was achieved in 86,5 % pts in the AF group and 74.1% of those were healed even with vaginal fistulas. Conclusion There was no significant difference in the healing rate of both methods (p= 0,202). AF procedure could be beneficial in vaginal fistulas, where MSC therapy is contraindicated. MSC therapy is useful in the case of chronic changes of rectal mucosa, anorectal stenosis and the presence of 2 internal openings, where AF procedure is not performable. High success rate in both groups may be conditioned by good preparation of patients (multiple previous drainages) and stable luminal disease (stable conservative treatment).

Association of Neutrophil Extracellular Traps with Fistula Healing in Patients with Complex Perianal Fistulizing Crohn's Disease.

Perianal fistulizing Crohn's disease [pfCD] is a disabling phenotype of Crohn's disease [CD] with suboptimal outcomes. We assessed neutrophil extracellular traps [NETs] in perianal fistulas and implicated their roles in pfCD healing. Patients with complex pfCD who developed preplaced seton drainage were recruited during the verified maintenance of remission in CD. Fistula tracts were sampled during definitive surgery plus seton removal. Patient demographics, CD classification, medication strategy and healing of pfCD were recorded. RNA sequencing was applied for transcriptomic profile analysis. NET components, including myeloperoxidase [MPO], neutrophil elastase [NE] and citrullinated histone H3 [CitH3], were identified using immunofluorescence. Serum infliximab [IFX], anti-IFX antibodies, and tissue levels of IFX, adalimumab [ADA], MPO and CitH3 were determined using enzyme-linked immunosorbent assays. Peptidyl arginine deiminase IV [PAD4], tumour necrosis factor [TNF]-α, and NE were detected using immunohistochemistry. Gene expression levels of PAD family members were assessed with quantitative PCR. Twenty-one patients were included, 15 of whom adopted IFX as maintenance treatment. RNA-sequencing revealed differences in neutrophil associated pathways between unhealed and healed fistulas. NET components [MPO/NE/CitH3] were detectable in the fistulas and were parallel with the levels of PAD4. Eleven of 21 [52%] patients experienced complete healing of the pfCD 108 weeks post-operatively. Fistula NETs were significantly increased in patients with unhealed pfCD. Increased NETs were associated with abundant TNF-α production and the absence of IFX in fistulas. NETs exist in pfCD fistulas, which are associated with unhealed post-operative fistulas in pfCD, suggesting their prognostic roles in pfCD.

Predictive Factors Affecting Recurrence of Anal Fistula after LIFT Procedure.

To determine the predictive factors affecting the recurrence or persistence of anal fistula of demographic and technical variables. Descriptive study. Department of General Surgery and Radiology, Private Ortadogu Hospital General, Turkey, between 2014 and 2020. The recurrence, persistence, and complication rates of 176 patients who underwent LIFT were compared with demographic and technical data by multivariate logistic regression analysis. Inclusion criteria were patients with anal fistula cryptoglandular origin. Exclusion criteria included patients with intersphincteric fistula, rectovaginal fistula, abscess, pilonidal sinus fistula, and inflammatory bowel disease. Recurrence was defined as the opening of a fistula that persisted after 3 months. The mean age was 38.6±9.0 years. The mean BMI was 31.9±5.7 Kg/m2. There were no statistically significant differences between the two groups concerning, age, the complexity of fistula tract(s), the surgical technique of suture versus ligation, operation time, and seton placement duration. Twenty-three patients had previous fistula surgery. Twenty-One patients had previously required seton drainage. Higher BMI, being male, having a prior fistula surgery, and having a height IFO >15 were independent risk factors for recurrence (OR =1.28, 5.69, 23.39, and 15.38 respectively). Higher BMI, male gender, having a prior fistula surgery, and having a height IFO >15 were independent risk factors for recurrence. LIFT, Anal fistula, Recurrence, Wexner incontinence score (WIS), Male, Prior fistula surgery, height 1FO.

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.

Cutting seton versus decompression and drainage seton in the treatment of high complex anal fistula: a randomized controlled trial

This study aimed to compare the efficacy between decompression and drainage seton (DADS) and cutting seton (CS) in the treatment of high complex anal fistula. Patients were randomly assigned 1:1 to DADS or CS group. The primary outcome was the rate of wound healing. Second outcomes included time taken to return to work, postoperative pain, the severity of fecal incontinence and other complications. A total of 120 patients with a mean age of 39 years were included. There was no significant difference in the rate of complete wound healing at 1 year. The mean time taken to return to work was 5 ± 2 days in DADS group, shorter than CS group (10 ± 3, p < 0.001). Mean vaizey incontinence score and the post-operation pain in DADS group was significantly lower than CS group. No significant difference was found between two groups in the incidence of complications. DADS is as effective as Cutting seton for the treatment of high complex anal fistula but is associated with less postoperative pain and better sphincter function preserving.

Pilonidal sinus laser-assisted closure (PiLAC) - a low-morbidity alternative to excision with excellent long-term outcomes.

Recurrence after surgery for pilonidal sinus disease is a recognised problem and patients often re-present months after discharge. We routinely treat primary and recurrent pilonidal sinus disease with Pilonidal sinus Laser-Assisted Closure (PiLAC). Long-term outcomes following PiLAC surgery was examined following clinical and telephone review. All patients undergoing PiLAC as a day-case between April 2016 and July 2019 were included. Patients were followed up in a nurse-led clinic until complete healing or recurrence. A prospective database and retrospective audit of notes combined with longer-term follow-up by telephone were used. A total of 35 patients underwent PiLAC, median age 28 (18-53 years), 28 males:7 females. A total of 28 patients had long-term (>60days) follow-up, mean 407 days (range 67-887 days); 25/28 patients (89.3%) had healed with no recurrence on long-term follow-up. Of these 28 patients, 11 were first presentation of pilonidal disease and underwent PiLAC as their first treatment, with a 91% heal rate long term. A total of 15 patients had seton drainage prior to PiLAC, with a 93% heal rate versus no seton (83%). Fisher's exact test showed no significant difference between sex, new/recurrent pilonidal disease and seton placement (p>0.05). Healing after PiLAC for the treatment of primary and recurrent pilonidal sinus disease is preserved with excellent long-term outcomes. We recommend it as an alternative to surgical excision.

P692 Clinical, therapeutic and evolutionary profile of fistulizing ano-perineal lesions in Crohn’s disease

Abstract Background Ano-perineal lesions (APLs) during Crohn’s disease (CD) are frequent and varied. Ano-perineal fistulas (APF) are the most common and severe manifestations. They are associated with increased morbidity and considerable impairment of quality of life. Their management is not always easy despite therapeutic advances, particularly anti-TNFα.The aim of our work was to describe the epidemiological profile, the therapeutic modalities and the evolutionary aspects of APF during CD. Methods This was a retrospective, descriptive, single-center study collecting records of patients followed for CD with APF between January 2010 and December 2020. The patients had a proctological examination and a perineal MRI. We recorded clinical, endoscopic, radiological data, therapeutic management and clinical response to the initial therapeutic regimen. Complete remission was defined as closure of all initially productive fistulas, partial response was defined as closure of more than 50% of fistulas. Therapeutic failure was defined as closure of less than 50% of the initially productive fistulas. Results 83 patients followed up for CD with APLs were collated of which 38 had APF (45.7%). The mean age was 42 years [26 - 73] with a sex ratio of 0.4. Active smoking was noted in six patients (15.8%). In 55.3% of cases, PAF was present at the time of diagnosis of CD (n=21).17 patients had developed one or more PAFs during the course of their disease with a mean delay of seven years [1 - 29]. APFs were associated with luminal involvement in 94.7% of cases, with ileal location in 10 patients (26.3%), colonic location in 13 patients (34.2%) and ileocolic location in 13 patients. The APFs were perianal in 34cases, vulvovaginal in five cases and gluteal in one case. There were complex fistulas in 92.1% of cases. The number of external orifices at the time of diagnosis was respectively: 1 orifice in 63.2% of cases, 2orifices in 26.3% of cases and more than two orifices in 10.5% of cases. A perineal abscess was associated in 44.7% of cases and anorectal stricture was observed in 7.9% of patients. Seton drainage was performed in 86.6% of patients. All patients with complex APF had received anti-TNFα after disappearance of 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, a complete remission was observed in 14 patients (36.8%), a partial response was noted in 13 patients (34.2%). 11 patients (28.9%) were in therapeutic failure. Conclusion In our study, APFs during CD account for almost half of all APLs.Thus, the development of local therapeutic means proves to be of necessity in order to increase the efficacy of biotherapies and to accelerate the healing of APFs.