Fistula Healing Rate Research Articles

P516 Discrete choice experiment to examine patient preferences for surgical interventions in patients with Crohn’s perianal fistulas: results from a global burden of illness study

Abstract Background Perianal fistulas (PAF) are a common complication of Crohn’s disease (CD) and patients with Crohn’s perianal fistulas (CPF) experience low health-related quality of life and a higher burden of symptoms than patients with CD without PAF (non-PAF CD). Treatment options for PAF, including medical and surgical interventions, are associated with high rates of relapse or failure. This global study assessed the burden of illness in patients with CPF compared with patients with non-PAF CD. Here, we present data on patient satisfaction with currently available PAF treatments and the attributes that drive treatment choice for patients with CPF. Methods This cross-sectional study was conducted in seven countries (France, Germany, Spain, UK, Canada, Australia and Japan) in patients aged ≥21 and ≤90 years with self-reported physician-diagnosed CD. Patients were classified as non-PAF CD (cohort 1) or CPF without PAF-related surgery (cohort 2) or CPF with PAF-related surgery (cohort 3). Using a web-enabled questionnaire, patient satisfaction with current PAF treatment options was recorded using a 1–9 scale and relative treatment attribute preferences were assessed via a discrete choice experiment (DCE) that included six attributes (Figure 1). Patients evaluated two treatment profiles at a time (“choice tasks”) to identify their most preferred treatment of the choices available. Data were analysed using descriptive statistics. Results A total of 929 patients were recruited, 620 with non-PAF CD and 309 with CPF. Of those with CPF (cohort 2, n=174; cohort 3, n=135), 68% were male, 65% were aged 21–40 years and 83% were currently taking CD-related medication. The median number of PAF was the same in cohorts 2 and 3 (both 2.0), although cohort 3 had a higher proportion of patients with active PAF (119/135 [88%]) compared with cohort 2 (136/174 [78%]; p =0.022). In cohort 3, 105/135 (78%) patients had ≥3 PAF-related procedures/surgeries, and ≥1 and >3 post-operative complications were experienced by 117/135 (87%) and 34/135 (25%) patients, respectively. Mean satisfaction scores were moderate for the majority of PAF treatment options and similar in both cohorts (range 6.2–6.9), although cohort 3 had significantly less satisfaction with long-term seton placement than cohort 2 (6.2 vs 6.7, respectively; p =0.035). Among the tested attributes, post-operative discomfort and fistula healing rate were the most important attributes influencing treatment choice (Figure 1). Conclusion In this study, patients with CPF had moderate satisfaction with PAF treatment options, regardless of surgical intervention. The DCE demonstrated that patients preferred interventions with better healing rates and lower post-operative discomfort compared to other attributes tested.

P374 Front loading infliximab dosing regimen improves outcomes in Crohn’s Disease perianal fistulas

Abstract Background Higher infliximab maintenance trough levels are found to be associated with higher perianal fistula healing rates in Crohn’s Disease. The relevance of accelerated front loading dosing in perianal fistula has not been determined. This study aimed to establish whether front loading with a higher dose infliximab regime at induction is associated with better fistula outcomes. Methods Crohn’s Disease patients with perianal fistulas treated with infliximab in a tertiary referral centre IBD unit were included. Patients were categorised as standard or front loading based on induction dose infliximab of, 5mg/kg or, 10mg/kg. The target for infliximab maintenance trough levels was >10mcg/mL. The primary outcome was the need for reintervention (defined as repeat abscess drainage, seton re-insertion, diverting stoma or proctectomy) at, 12 months post initiation of treatment. Secondary outcomes were the proportion of patients having clinical healing, radiologic healing and combined clinical and radiologic healing. Drug levels post induction and post first maintenance were evaluated. The proportion of patients needing dose escalation or de-escalation were also assessed. Chi-squared or Fisher exact tests were used to compare categorical variables and Kaplan-Meier survival curves were plotted for re-intervention free survival. Results Seventy-nine patients were included in analysis (Males: Females, 36:43, median age with fistula = 31). Seventeen (22%) of patients received a front loading dose of, 10mg/kg while sixty-two (79%) patients received the standard dose of, 5mg/kg among whom, 70% had dose escalation. Need for reintervention was significantly lower in patients who received a front loading dosing schedule compared to the standard dose (2/17 (12%) vs, 26/62 (42%), p=0.02) (Figure, 1). Higher clinical fistula healing rates were observed with front-loading dosing (82% vs, 45%, p=0.008). Radiologic healing in those who had follow up Magnetic Resonance Imaging (MRI) was not significant between both groups (8/17 (47%) vs, 20/62 (32%), p=0.133). Target therapeutic infliximab levels at maintenance was achieved in, 14/17 (82% of the patients receiving front loading dosing, while this was achieved in only, 2 of the, 43 (5%) tested patients with standard dosing. Reintervention requirement rates were higher in those patients with suboptimal maintenance levels (17/44 (39%) vs, 2/16 (12.5%), p=0.01). The Kaplan-Meier curves confirm that the front loading dosing regimen does prevent the need for reintervention (p=0.03) (Figure 2). Figure1: Figure 2: Conclusion Front loading with higher infliximab dose achieves better fistula healing and reduce the need for reinterventions in Crohn`s disease with perianal fistula.

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

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

A randomized trial of negative pressure wound therapy technology combined with intermittent instillation in the treatment of neck anastomotic leakage after esophageal cancer surgery.

This study aimed to examine the effects of applying the negative pressure wound therapy (NPWT) combined with intermittent instillation (NPWTi) in patients with cervical anastomotic leakage (AL) after esophageal cancer surgery. From July 2019 to June 2021, 64 patients undergoing AL after esophageal cancer surgery were selected from our Hospital's Thoracic Department, and randomly allocated to the conventional nursing group (20 patients), the hospital central NPWTi group (23 patients), and the portable NPWTi group (21 patients). The hospital central NPWTi group was treated with central negative pressure combined with intermittent instillation, and the portable NPWTi group was treated with portable negative pressure combined with intermittent instillation. Indicators of fistula healing, healing days, treatment costs, comfort, and nursing satisfaction were examined in each group. The fistula healing rate, healing days, nursing satisfaction, and comfort level of the hospital central NPWTi group and the portable NPWTi group were better than those of the conventional nursing group (P<0.05). There was no difference in the fistula healing rates and healing days between the hospital central NPWTi group, and the portable NPWTi group (P>0.05). The treatment costs of the hospital central NPWTi group were lower than those of the portable NPWTi group (P<0.05). Negative pressure treatment technology combined with the intermittent instillation of the neck anastomotic fistula improved the fistula microenvironment, strengthened the sterilization effect, drained the leachate effectively, shortened the fistula healing time, improved the fistula cure rate, and increased patients' satisfaction with nursing. In relation to the negative pressure source, there was no difference in the therapeutic effects of hospital central NPWTi compared to the portable negative pressure meter, but the hospital central NPWTi treatment costs were lower and patients' acceptance of NPWT instillation was higher. Thus, central NPWT instillation treatment is worthy of promotion. Chinese Clinical Trial Registry ChiCTR2100052240.

Therapeutic Drug Monitoring of Biologics in IBD: Essentials for the Surgical Patient.

Despite significant development in the pharmacological treatment of inflammatory bowel diseases (IBD) along with the evolution of therapeutic targets and treatment strategies, a significant subset of patients still requires surgery during the course of the disease. As IBD patients are frequently exposed to biologics at the time of abdominal and perianal surgery, it is crucial to identify any potential impact of biological agents in the perioperative period. Even though detectable serum concentrations of biologics do not seem to increase postoperative complications after abdominal procedures in IBD, there is increasing evidence on the role of therapeutic drug monitoring (TDM) in the perioperative setting. This review aims to provide a comprehensive summary of published studies reporting the association of drug concentrations and postoperative outcomes, postoperative recurrence (POR) after an ileocolonic resection for Crohn’s disease (CD), colectomy rates in ulcerative colitis (UC), and perianal fistulizing CD outcomes in patients treated with biologics. Current data suggest that serum concentrations of biologics are not associated with an increased risk in postoperative complications following abdominal procedures in IBD. Moreover, higher concentrations of anti-TNF agents are associated with a reduction in colectomy rates in UC. Finally, higher serum drug concentrations are associated with reduced rates of POR after ileocolonic resections and increased rates of perianal fistula healing in CD. TDM is being increasingly used to guide clinical decision making with favorable outcomes in many clinical scenarios. However, given the lack of high quality data deriving mostly from retrospective studies, the evidence supporting the systematic application of TDM in the perioperative setting is still inconclusive.

Simplified dressing change after loose combined cutting seton surgery for high anal fistula: a prospective, single center randomized controlled study.

High anal fistula (HAF) is a refractory infectious disease. Surgery is the most effective way to treat HAF. Dressing change is an indispensable part of the rehabilitation process after surgery. The purpose of this study is to provide feasibility and evidence of safety for the implementation of a simplified dressing change after loose combined cutting seton (LCCS) surgery and to offer a better method for clinical treatment and postoperative rehabilitation of HAF. In this single-blind randomized controlled trial, 76 patients diagnosed with HAF will be randomly divided into two groups: the simplified dressing change group (n=38) or the traditional debridement and dressing change group (n=38). Compared with traditional debridement and dressing change, simplified dressing change was conducted without mechanical debridement and disinfection. All patients were treated surgically with the LCCS and dressing change. Postoperative follow-up will be carried out on the 3rd, 7th, 14th, 21st, and 180th day after the operation. The primary outcomes will be: complete healing rate of wound and fistula, long-term recurrence rate, poor wound healing rate, and complete wound healing time. The following secondary outcomes will be evaluated: postoperative pain using a visual analogue scale (VAS) score, wound secretions, edema, granulation shape, depth of wound, duration of each dressing change, and incidence of adverse events. Dressing change after HAF surgery is a necessary stage of recovery after anorectal surgery. Effective dressing change can reduce false healing and increase the cure rate. However, traditional dressing change takes a long time, and the patient endures severe pain. We have found that the dressing change process can be simplified in the clinic for patients treated with LCCS. In particular, simplification of the dressing change process may be related to the unobstructed drainage provided by the combination of LCCS and the separation of the dotted line. We will treat HAF using LCCS and compare the simplified dressing change method after the operation with traditional routine debridement and dressing change to demonstrate whether the simplified dressing change can be used in patients with HAF treated with LCCS. ChiCTR2100047312.

External sphincter-sparing anal fistulotomy (ESSAF): a simplified technique for the treatment of fistula-in-ano

Fistula-in-ano due to cryptoglandular disease is a common condition. While a simple anal fistula can be treated successfully by a fistulotomy, the risk of potential damage to the anal sphincters and subsequent poor functional outcomes persist in a large portion of patients with complex fistulae. Several sphincter-preserving treatment procedures have been described for complex fistulae over the past 3 decades, with variable results and complication rates, and no procedure is proven to be superior to the others. We developed external sphincter-sparing anal fistulotomy (ESSAF), a reproducible simple modification of the ligation of intersphincteric fistula tract (LIFT) technique for the treatment of complex fistula-in-ano.. The aim of the present study was to describe the technique and our outcomes. This was a retrospective review of all patients who underwent ESSAF for a complex anal fistula at our institution from January 2014 to December 2019. The primary outcome measure of this study was the primary fistula healing rate. Secondary outcome measures included fecal and/or gas incontinence and postoperative complications. During the ESSAF procedure, the mucosa and skin overlying the fistula tract are incised to allow complete exposure of the sphincter complex. Then the internal sphincter muscle fibers overlying the tract are divided and the tract is meticulously curetted and debrided. Next, the internal opening of the tract traversing the external sphincter muscle is suture-ligated with absorbable sutures. Then, a minimal amount of mucosa is advanced and the incision is partially closed with absorbable sutures, while its external portion is left open for drainage. Fifty-nine patients [43 males, median age was 50years (range 36-63years)] underwent ESSAF for complex anal fistula during the study period. Mean follow-up was 12 ± 14.7months. Of the 59 patients, 42 (71.2%) experienced fistula closure, with a median healing time of 8weeks (IQR 4-16weeks). None of the patients developed significant anal incontinence following the procedure. One patient (1.7%) suffered from soiling and another patient (1.7%) developed postoperative bleeding. There were no infectious complications. Of the 17 patients (28.8%) who failed to heal successfully, 9 (15.2%) did not heal primarily and 8 (16%) experienced recurrence after complete healing. Thirteen (76%) of these patients underwent reoperation with complete recovery after ESSAF (n = 4), fistulotomy (n = 8) or endorectal advancement flap (ERAF) (n = 1). Overall ESSAF initiated recovery in 93.2% of the patients. ESSAF is a feasible, safe, reproducible and effective sphincter-sparing procedure for the treatment of complex anal fistulae.

Lessons learned from an audit of 1250 anal fistula patients operated at a single center: A retrospective review.

BACKGROUNDA complex anal fistula is a challenging disease to manage.AIMTo review the experience and insights gained in treating a large cohort of patients at an exclusive fistula center.METHODSAnal fistulas operated on by a single surgeon over 14 years were analyzed. Preoperative magnetic resonance imaging was done in all patients. Four procedures were performed: fistulotomy; two novel sphincter-saving procedures, proximal superficial cauterization of the internal opening and regular emptying and curettage of fistula tracts (PERFACT) and transanal opening of intersphincteric space (TROPIS), and anal fistula plug. PERFACT was initiated before TROPIS. As per the institutional GFRI algorithm, fistulotomy was done in simple fistulas, and TROPIS was done in complex fistulas. Fistulas with associated abscesses were treated by definitive surgery. Incontinence was evaluated objectively by Vaizey incontinence scores.RESULTSA total of 1351 anal fistula operations were performed in 1250 patients. The overall fistula healing rate was 19.4% in anal fistula plug (n = 56), 50.3% in PERFACT (n = 175), 86% in TROPIS (n = 408), and 98.6% in fistulotomy (n = 611) patients. Continence did not change significantly after surgery in any group. As per the new algorithm, 1019 patients were operated with either the fistulotomy or TROPIS procedure. The overall success rate was 93.5% in those patients. In a subgroup analysis, the overall healing rate in supralevator, horseshoe, and fistulas with an associated abscess was 82%, 85.8%, and 90.6%, respectively. The 90.6% healing rate in fistulas with an associated abscess was comparable to that of fistulas with no abscess (94.5%, P = 0.057, not significant).CONCLUSIONFistulotomy had a high 98.6% healing rate in simple fistulas without deterioration of continence if the patient selection was done judiciously. The sphincter-sparing procedure, TROPIS, was safe, with a satisfactory 86% healing rate for complex fistulas. This is the largest anal fistula series to date.

Transanal opening of the intersphincteric space: a novel sphincter-sparing procedure to treat 325 high complex anal fistulas with long-term follow-up.

Sepsis in the intersphincteric plane behaves like an abscess in a closed space and is present in most complex fistulas. Ignoring this sepsis is a cause of recurrence. Complex fistulas can be successfully managed by transanal opening of the intersphincteric space (TROPIS) into the anal canal. The long-term efficacy of the TROPIS procedure was analysed in an exclusive cohort of high complex anal fistulas. All consecutive patients operated for a high complex fistula-in-ano were included prospectively. Preoperative MRI scans were obtained for all the patients. The intersphincteric space and internal opening was laid open into the anal canal while preserving the external sphincter. The external tracts were thoroughly curetted and cleaned. Fistula healing rate and objective incontinence scores (preoperatively and during long-term follow-up) were analysed. A total of 325 patients (age 39.9±10.9years, 292 men) were operated with TROPIS and had a follow-up of 7-67months (median 36months). In the cohort, 67.4% (219) had recurrent fistulas, 82.8% (269) had multiple tracts, 36.3% (118) had horseshoe tracts, 37.5% (122) had associated abscesses and 24% (78) were supralevator fistulas. Nineteen patients were excluded. Fistulas healed completely in 78.4% (240/306) of patients and did not heal in 21.6% (66/306) of patients. 36/66 of these patients were operated again and the fistulas healed in 28 patients. Thus, the overall healing rate was 87.6% (268/306). The mean preoperative and postoperative incontinence scores were 0.085±0.35 and 0.119±0.48 respectively (P=0.38). The healing rate of fistulas with associated acute abscesses was similar to the fistulas without abscesses (87% vs. 88%, P=0.85). Transanal opening of the intersphincteric space is a safe and highly effective sphincter-sparing procedure to manage high complex fistulas-in-ano.

Management of perianal fistula in inflammatory bowel disease: identification of prognostic factors associated with surgery.

As one of the clinical manifestations of inflammatory bowel disease (IBD), perianal fistula disease (PFD) can potentially impact the patient quality of life. The management of PFD employs a multidisciplinary approach which includes antibiotics, biological therapies, immunomodulators, and surgery. We analyzed the outcome and prognostic factors of anal fistula surgery in IBD patients. We conducted a retrospective study of IBD patients undergoing elective surgery for anal fistula between January 2015 and December 2018 at our University Department of Surgery. We collated demographic factors, disease activity, imaging (MRI and endoanal ultrasound), surgical interventions, and medical treatment assessing the rate of fistula closure and fecal incontinence, 2 months and 1 year after surgery. Thirty-five IBD patients with anal fistula underwent surgery (28 Crohn's disease, four ulcerative colitis, and three indeterminate colitis). Twenty-seven patients presented with complex fistulas and eight with simple fistulas with 10 patients undergoing single-stage surgery. In 25 patients, a two-stage surgical approach was planned and performed (draining seton plus medical treatment and then second-stage surgery with curative intent). At 1 year of follow-up, the fistula healing rate was 50% for single-stage surgery and 60% for two-stage surgery (P = 0.09). Overall, 19.2% of patients developed postoperative fecal incontinence. A time interval greater than 12 months between surgeries is a favorable prognostic factor for fistula healing with the two-stage approach (P = 0.002). In our retrospective study, two-stage surgery in IBD patients presenting with complex perianal fistulous disease results in a better medium-term outcome with a longer time interval between surgeries.

Comparison of the Efficacy of the Various Treatment Modalities in the Management of Perianal Crohn's Fistula: A Review.

Crohn's disease (CD) is a transmural inflammatory bowel disease (IBD) that can affect any part of the gastrointestinal (GI) tract. With the disease's progression, adhesions and transmural fissuring, intra-abdominal abscesses, and fistula tracts may develop. An anal fistula (or fistula-in-ano) is a chronic abnormal epithelial lined tract communicating the anorectal lumen (internal opening) to the perineal or buttock skin (external opening). The risk of fistula development varies from 14%-38%. It can cause significant morbidity, which adversely impacts the quality of life. It is mostly believed that an anal crypt gland infection causes anal abscesses, leading to fistula development. Crohn's disease's pathogenesis involves Th1 and Th17 hypersensitivity due to an unknown antigen within the intestinal mucosa.Evidence to support this review was gathered via the Pubmed database. Search terms used were combinations of "Perianal fistula," "seton," "immunotherapy." Studies were reviewed and cross‐referenced for additional reports.Setons are surgical thread loops passed from the external to the internal opening of the fistula tract and exteriorized through the anorectal canal, facilitating abscess drainage and inciting a local inflammatory reaction, thus promoting the resolution of the fistula. Biologicals such as anti-tumor necrosis factor (TNF) antibody (infliximab, adalimumab, certolizumab), anti-IL-12/23 (ustekinumab), and anti-α₄β₇ integrin antibody (vedolizumab) have been approved for Crohn's disease targeting the Th1/Th17-mediated inflammation. Other therapeutic modalities are fistulotomy, cyanoacrylate glue, bioprosthetic plugs, mucosal advancement flap, ligation of inter-sphincteric fistula tract (LIFT), diverting stoma, proctectomy, video-assisted anal fistula treatment (VAAFT), and fistula laser closure (FiLaC).Our review found that chronic seton therapy should be the primary approach, especially if the patient has a perianal abscess. It has a low incidence of re-intervention, recurrent abscess formation, and side-branching of the fistulous tract, with preservation of the fistulous tract's patency and cost-effectiveness. The major disadvantage of seton therapy is the discomfort and time to achieve stability. Among the biologicals, infliximab is the only therapy which has a statistically significant effect on the healing rate of perianal Crohn's fistula compared to placebo, but the major disadvantage associated with anti-TNF as sole therapy is high re-intervention rate, prolong maintenance therapy, high recurrence rate, and severe side effects. We hypothesize that the two aspects should be addressed concurrently to increase the fistula healing or closure rate. First, the seton should be used as initial therapy to maintain tract patency to allow abscess drainage and minimize the intestinal flora colonization within the tract mucosa, thereby leukocytic infiltration and propagation of inflammation within the tract. The second aspect that has to be considered is that we should target the initial stimulation of the Th1/Th17 mediated hypersensitivity instead of a factor/cytokine involved in the inflammation mediation. Although the unknown antigen triggering such hypersensitivity is not clear, we could target the RAR-related orphan receptor γ (RORγ)-T (transcription factor involved in activation of Th17 cells) and the T-bet (transcription factor involved in activation of Th17 cells) within the GI mucosa by a novel target immune therapy.

P071 Fistula Healing After Fecal Diversion Surgery in Perianal Crohn's Disease; a Case Series.

BACKGROUND: Perianal fistula are seen in 25% of patients with Crohn's disease and are often refractory to medical therapy. Fecal diversion is used to treat perianal fistula, with 63% in clinical improvement, however data on fistula healing rates are often not reported. This case series aims to evaluate the response of complete fistula healing in complex perianal Crohn's disease after fecal diversion. METHODS: Patients with perianal Crohn's disease who underwent fecal diversion surgery from June 1, 2016 to June 1, 2020 with colorectal surgeons at UC Davis were selected through electronic medical record chart extraction using ICD-10 and CPT codes. RESULTS: Eleven patients with refractory perianal fistula underwent fecal diversion surgery from June 1, 2016 to June 1, 2020. Fistula healing was evaluated through imaging or exam under anesthesia. One patient was lost to follow up after surgery and not included in the outcomes. Time to follow up ranged from 4 to 24 months, with a mean of 11 months. Patient were aged 22–60 years. 5/11 were male. Ten of 11 patients were on biologic therapy at time of surgery, 4/10 (40%) had complete fistula healing, 6/10 (60%) had persistent fistula, and 3/10 (30%) were readmitted within 90 days for complications. Most frequent complications observed were peristomal wounds/skin infection (3/10), high ostomy output/dehydration (2/10), bowel obstruction (1/10). Two patients required proctectomy. CONCLUSION: Fistula healing rates after fecal diversion were low, at 40% and is accompanied by frequent complications such as output high ostomy.

Efficacy and Safety of Mesenchymal Stem Cells in Treatment of Complex Perianal Fistulas: A Meta-Analysis.

Complex perianal fistula is a highly debilitating and difficult to treat condition. Local mesenchymal stem cell (MSC) therapy for perianal fistula has shown considerable promise but still remains controversial. Therefore, we performed the meta-analysis to evaluate the efficacy and safety of local MSC therapy for complex perianal fistula. PubMed and Embase databases were searched for published randomized clinical trials (RCTs) that reported local MSC therapy for complex perianal fistulas. The effectiveness and safety data analysis was conducted using RevMan5.3. Subgroup analyses were performed based on the characteristics of the studies. Seven RCTs with 730 participants were included. Local MSC treatment showed significantly higher healing rate (HR) of perianal fistulas compared to control (odds ratio (OR) = 2.03; 95% confidence interval (CI) 1.50, 2.74; P < 0.00001). MSCs combined with fibrin glue therapy can improve the HR compared with fibrin glue alone (OR = 3.27; 95% CI 1.15, 9.28; P = 0.03). Subgroup analyses showed that local therapy can improve the HR in patients with perianal fistulas associated with Crohn's disease (CD) (OR = 2.05; 95% CI 1.41, 3.00; P = 0.0002) and cryptoglandular origin (no-Crohn) (OR = 2.98; 95% CI 0.86, 10.29; P = 0.08). The pooled OR for studies that combined reepithelialization of the external opening with pelvic magnetic resonance imaging (MRI) to evaluate the healing of fistulas was 1.77 (95% CI 1.28, 2.45; P = 0.0006). The pooled OR for studies where fistula healing was defined as complete reepithelialization of external openings was 5.92 (95% CI 1.34, 26.15; P = 0.02). Both autologous MSCs (OR = 3.19; 95% CI 1.05, 9.65; P = 0.04) and allogeneic MSCs (OR = 1.97; 95% CI 1.34, 2.91; P = 0.0006) can obtain higher HR for perianal fistula compared with control. The adipose-derived MSC group can obtain higher HR than the control group (OR = 2.29; 95% CI 1.38, 3.79; P = 0.001). There were no significant differences in adverse events (AEs) (OR = 1.06; 95% CI 0.71, 1.59; P = 0.77). None of the adverse events was judged to be related to MSCs. Our study supported that local MSC therapy alone or combined with fibrin glue is safe and efficacious for complex perianal fistula. In the future, more RCTs are needed to confirm this conclusion.

Loose combined cutting seton for patients with high intersphincteric fistula: a retrospective study.

BackgroundAchieving a complete cure while maintaining continence constitutes a considerable challenge in the treatment of patients with high anal fistula. This study aimed to evaluate the effectiveness of loose combined cutting seton (LCCS) for treating patients with high intersphincteric fistula.MethodsConsecutive patients with high intersphincteric fistula who underwent LCCS were retrospectively enrolled. Patient data including demographics, medical history, comorbidities, details of the fistula, operative procedure, and prognosis were collected. Postoperative pain was assessed using a visual analog scale (VAS), which ranged from 0 (no pain) to 10 (extremely severe pain). The severity of fecal incontinence was assessed using the Wexner Continence Grading Scale, with a total score ranging from 0 (no incontinence) to 20 (complete incontinence). The primary outcome was the healing rate of fistula. Secondary outcomes included the recurrence rate of fistula and the severity of fecal incontinence.ResultsThe 22 patients (male: female =18:4) in our study had a median follow-up of 55 (range, 32–568) days. The healing rate was 100%, and none of the patients experienced fistula recurrence. At the follow-up visit, 19 patients (86.4%) reported no fecal incontinence. The median total Wexner score was 0. 95.5% patients had VAS score of 0 and only 1 patient (4.5%) had a VAS score of 1, which indicated a low level of postoperative pain.ConclusionsLCCS achieved a high healing rate with an increased level of continence, as well as a low level of postoperative pain, in most patients with high anal fistula in our study. Further randomized controlled trials are needed to confirm the effectiveness of this novel seton-based technique.

Effectiveness of Infliximab on Deep Radiological Remission in Chinese Patients with Perianal Fistulizing Crohn's Disease.

Information concerning deep radiological healing of perianal fistulas in Chinese patients with CD is limited. The present study aimed to establish the effectiveness of infliximab on CD-related perianal fistulas using magnetic resonance imaging (MRI) and identify predictors of deep radiological remission of fistulas. We retrospectively reviewed patients with CD with draining perianal fistulas treated with infliximab and included only those who underwent clinical assessment and MRI before and after infliximab therapy. Among 178 patients who underwent repeated MRI and clinical assessment, 65.2% had complex fistulas. Post-infliximab therapy, 55.1% of patients with perianal fistulizing CD showed clinical remission and 26.4% presented a clinical response; 38.2% had deep radiological remission, and 34.3% had a partial response based on the Ng score; the Van Assche scores decreased obviously compared with baseline. Prolonged infliximab infusion (18 times) presented higher radiological remission rates in patients with CD with complex fistulas. Concomitant treatment with azathioprine increased the fistula healing rate compared with infliximab alone (50% vs. 36.9%, P < 0.001). Younger age at diagnosis of CD, proctitis and requiring perianal surgery were identified as predictors of poor deep radiological remission of fistulas. Eight of ten patients who stopped infliximab and switched to an alternative agent retained a status of fistula healing in the first year of follow-up. Infliximab induced deep radiological remission of perianal fistulas in Chinese patients with CD. Routine MRI should be used to monitor fistula healing. Patients with younger age at diagnosis of CD, proctitis, and/or requiring perianal surgery should receive combined therapy and careful monitoring.

Post surgical rectovaginal fistula: who really benefits from stoma diversion?

To analyze the role of stoma diversion and timing of stoma maintenance in the healing of post-surgical Recto Vaginal Fistulae (psRVF). A retrospective analysis of a prospectively maintained registry. All patients with a psRVF diagnosed at IRCCS Sacro Cuore-Don Calabria Hospital of Negrar di Valpolicella from January 2002 to December 2016 were analyzed. The baseline treatment was a fecal diversion. Patients were divided into two groups according to healing time: < 6months (Group 1) or > 6months (Group 2). 2043 women underwent rectal resections in the study period. We recorded 37 patients with psRVF (1.8%). Nineteen women (51.3%) healed (Group 1) within 6months. The median time of psRVF recovery in group 1 was 99.7days. Concomitant local treatment of the fistula did not influence the healing rate (p 0.8). Colostomies were significantly higher in group 1 (p 0.003). The size of the psRVF influenced the success rate of fistula healing with loop stoma (p 0.07). A multivariate analysis the presence of fever and pelvic abscess (pelvis sepsis) were significantly associated with diversion failure (p 0.035). A step-up approach with the maintenance of loop stoma at least for six months for all patients with psRVF could be changed. Patients with larger fistula and pelvic sepsis at index procedure should be addressed earlier to a specific second-level treatment.

Optimized timing of using infliximab in perianal fistulizing Crohn's disease.

Infliximab (IFX), as a drug of first-line therapy, can alter the natural progression of Crohn’s disease (CD), promote mucosal healing and reduce complications, hospitalizations, and the incidence of surgery. Perianal fistulas are responsible for the refractoriness of CD and represent a more aggressive disease. IFX has been demonstrated as the most effective drug for the treatment of perianal fistulizing CD. Unfortunately, a significant proportion of patients only partially respond to IFX, and optimization of the therapeutic strategy may increase clinical remission. There is a significant association between serum drug concentrations and the rates of fistula healing. Higher IFX levels during induction are associated with a complete fistula response in these patients. Given the apparent relapse of perianal fistulizing CD, maintenance therapy with IFX over a longer period seems to be more beneficial. It appears that patients without deep remission are at an increased risk of relapse after stopping anti-tumor necrosis factor agents. Thus, only patients in prolonged clinical remission should be considered for withdrawal of IFX treatment when biomarker and endoscopic remission is demonstrated, especially when the hyperintense signals of fistulas on T2-weighed images have disappeared on magnetic resonance imaging. Fundamentally, the optimal timing of IFX use is highly individualized and should be determined by a multidisciplinary team.

Long-term efficacy of bioprosthetic anal fistula plug in the treatment of transsphincteric anal fistula

Objective: To evaluate the long-term healing rate of transsphincteric anal fistula treated with anal fistula plug procedure and the risk factors affecting the healing of anal fistula. Methods: A retrospective case-control study was conducted to analyze the clinical data of 207 patients with transsphincteric anal fistulas who received anal fistula plug procedure at the Department of General Surgery, Beijing Chaoyang Hospital of Capital Medical University from August 2008 to September 2012. Inclusion criteria: (1) consistent with the diagnosis of transsphincteric anal fistula: the anal fistula passed through the internal and external sphincter; (2) complete data; (3) initial treatment with anal fistula plug procedure. Exclusion criteria: (1) acute rectal or perianal infection or poorly controlled focal infection; (2) recent incision and drainage of perianal abscess or spontaneous rupture of abscess; (3) patients with malignant tumor; (4) patients with Crohn's disease or ulcerative colitis; (5) patients with heart, liver, brain, lung or renal insufficiency; (6) cachexia due to various chronic wasting diseases; (7) patients could not tolerate surgery. Patients were followed up for anal fistula healing. The cumulative healing rate of patients with transsphincteric anal fistula was plotted using the Kaplan-Meier method, and the factors affecting anal fistula healing were explored by univariate and multivariate logistic regression analysis. Results: There were 186 males and 21 females with age of 15 to 69 (mean 38) years. The duration of anal fistula was 3-60 (mean 15) months. Three patients had a history of previous episodes of perianal abscess and underwent incision and drainage of perianal abscess (all more than 3 months). During follow-up ending on October 31, 2018, 72 patients (34.8%) were lost to follow-up. Among 135 patients who were successfully followed up, the average follow-up period was 96 (75-124) months. Seventy-five patients had anal fistula healing, with healing rate of 55.6%. Kaplan-Meier survival curve showed that the healing time of anal fistula was prolonged and finally stabilized at 55.6%. In the patients who failed initial treatment with anal fistula plug packing, there were 6 cases whose anal fistula healed spontaneously without other treatment. Among them, 3 cases healed spontaneously 2 years and 3 cases 3 years after operation without recurrence. From 2008 to 2012, the annual healing rates of anal fistula plug treatment were 3/6, 61.5% (24/39), 42.1% (24/57), 12/15 and 12/18, respectively. Multivariate logistic regression analysis showed that the duration of anal fistula≥6 months (OR=3.187, 95% CI: 1.361-7.466, P=0.008) was an independent risk factor for anal fistula healing after treatment with anal fistula plug. Conclusion: The long-term efficacy of anal fistula plug procedure in the treatment of transsphincteric anal fistula is positive, and this procedure should be implemented as soon as possible.

P586 Higher infliximab and adalimumab trough levels are associated with fistula healing in patients with fistulising perianal Crohn’s disease

Abstract Background Anti-TNF α agents, including infliximab (IFX) and adalimumab (ADA), are arguably the most effective medical therapies for fistulising perianal Crohn’s disease (CD). Increased rates of perianal fistula healing have been reported with increased IFX trough levels. Our study aimed to determine the correlation between perianal fistula healing and closure with IFX and ADA trough levels in fistulising perianal CD patients on maintenance therapy. Methods In this multi-centre retrospective cross-sectional study, we identified CD patients with perianal fistulae on maintenance IFX or ADA who had an IFX or ADA trough level within 3 months of clinical assessment. Data collected included demographics, serum IFX and ADA trough levels (mg/l) and concomitant medical and surgical therapy. The primary outcome was fistula healing, defined as a cessation in fistula drainage. The secondary outcome was fistula closure, defined as healing as well as closure of all external fistula openings. Receiver operating characteristic (ROC) curve analysis was performed to identify the IFX and ADA concentration cut-off points with combined maximal sensitivity and specificity that corresponded to fistula healing. Results A total of 123 patients (IFX = 72; ADA = 51) were included. Fifty-four (75.0%) patients on maintenance IFX achieved fistula healing and 22 (30.6%) achieved fistula closure. Patients who achieved fistula healing had significantly higher median IFX trough levels compared with patients who did not [6.2 (interquartile range 3.1 - 9.6) vs. 3.0 (0.3 - 6.2), (p = 0.007)]. The median IFX trough levels for patients with and without fistula closure were not significantly different [6.4 (2.9 - 9.8) vs. 4.9 (2.5 - 8.9), (p = 0.277)]. Forty (78.4%) patients on maintenance ADA achieved fistula healing and eighteen (35.3%) fistula closure. Patients who achieved fistula healing had a significantly higher median ADA level compared with those who did not [8.7 (6.6 - 12.0) vs. 5.4 (2.5 - 8.3), p = 0.007]. The median ADA trough levels for patients with fistula closure and without fistula closure were not significantly different [9.6 (6.7 – 12.0) vs. 7.7 (4.4–9.8), p = 0.098]. An IFX cut off point of 6.10mg/l was associated with healing (sensitivity 52%; specificity 78%; area under the curve (AUC) 0.72). An ADA cut off point of 7.05mg/l was associated with healing (sensitivity 70%; specificity 73%; AUC 0.77). Conclusion Higher IFX and ADA trough levels are associated with fistula healing. No association between IFX and ADA trough levels and fistula closure was seen, although larger numbers may be required. To the best our knowledge, this is the first study to demonstrate a significant association with both higher IFX and ADA levels with fistula healing in perianal CD.

Functional outcome and quality of life evaluation of graciloplasty for the treatment of complex recto-vaginal and recto-urethral fistulas.

Recto-vaginal (RVF) and recto-urethral (RUF) fistulas are infrequent but disabling conditions that severely affect patients' quality of life. Considering the high recurrence rate after conservative approaches, the best surgical treatment is still challenging. The aim of this study was to evaluate the outcome of graciloplasty to treat patients with complex RVF or RUF, and to investigate its effect on the quality of life. Fourteen patients with RVF and RUF who underwent graciloplasty between 2003 and 2017 were retrospectively enrolled. The main outcome was the healing rate of fistulas. Postoperative patients satisfaction was evaluated administering the Clinical Patient Grading Assessment Scale (CPGAS), SF-36 questionnaires and Changes in Sexual Functioning (CSF) questionnaires. The Wexner score was calculated in case of preoperative faecal incontinence. RVF and RUF were iatrogenic in 11 patients and due to Crohn's disease in 3 cases. After 1year of follow-up (IQR 10-14months), the success rate of the procedure was 78%. Out of three patients with RVF due to Crohn's disease, two healed after the procedure. Six months after surgery, all eight SF-36 domains significantly improved except for "body pain"; CSF score significantly increased from 35.5 (IQR 31-38.7) to 44 (IQR 37.7-48.5); CPGAS score improved from a median value of 0 (IQR 0-0) to 4 (IQR 3.2-4). The Wexner score was calculated only in 5 patients with preoperative faecal incontinence and it significantly decreased from a median value of 12 (IQR 11-14) to 5 (IQR 4-5). Graciloplasty could be considered as a first option treatment for complex or recurrent RVF and RUF. It shows a good healing rate even in case of unfavourable factors like Crohn's disease.