Perianal Fistulizing Disease Research Articles

The role of MRI in perianal fistulizing disease: diagnostic imaging and classification systems to monitor disease activity.

Perianal fistulizing disease, commonly associated with Crohn's disease, poses significant diagnostic and therapeutic challenges due to its complex anatomy and high recurrence rates. Radiological imaging plays a pivotal role in the accurate diagnosis, classification, and management of this condition. This article reviews the current radiological modalities employed in the evaluation of perianal fistulizing disease, including magnetic resonance imaging (MRI), endoanal ultrasound, and computed tomography (CT). MRI, recognized as the gold standard, offers superior soft tissue contrast and multiplanar capabilities, facilitating detailed assessment of fistula tracts and associated abscesses. CT, although less detailed than MRI, remains valuable in acute settings for detecting abscesses and guiding drainage procedures. This article discusses the advantages and limitations of each modality, highlights the importance of standardized imaging protocols, and underscores the need for interdisciplinary collaboration in the management of perianal fistulizing disease. Future directions include advancements in imaging techniques and the integration of artificial intelligence to enhance diagnostic accuracy and treatment outcomes.

Stem Cells and Stem Cell-Derived Factors for the Treatment of Inflammatory Bowel Disease with a Particular Focus on Perianal Fistulizing Disease: A Minireview on Future Perspectives.

Inflammatory bowel disease remains a difficult disease to effectively treat, especially fistulizing Crohn's disease. Perianal fistulas in the setting of Crohn's disease remain an area of unmet need with significant morbidity in this patient population. Up to one third of Crohn's patients will have perianal fistulizing disease and current medical and surgical interventions are of limited efficacy. Thus, most patients experience significant morbidity, narcotic use, and loss of employment and end up with multiple surgical interventions. Mesenchymal stem cells (MSCs) have shown efficacy in phase 3 clinical trials, but considerable infrastructure challenges make MSCs limited with regard to scalability in clinical practice. Extracellular vesicles, being derived from MSCs and capturing the secretome functionality of MSCs, offer similar physiological utility regarding mechanism, while also providing an off the shelf regenerative medicine product that could be widely used in daily clinical practice.

A236 THE EFFECTIVENESS AND SAFETY OF DUAL ADVANCED THERAPIES IN PATIENTS WITH INFLAMMATORY BOWEL DISEASE: A CASE-SERIES

Abstract Background Patients with inflammatory bowel disease (IBD) refractory to medical therapy and patients with IBD and concurrent extra-intestinal manifestations (EIMs) pose a challenge within gastroenterology. The small number of approved agents for IBD limits therapeutic options for this population. Utilizing a combination of newer biologic therapies with favourable safety profiles may provide a safe and efficacious option for treating patients with refractory disease or patients with well-controlled IBD but uncontrolled EIMs. Aims The aim of our study was to assess the safety and efficacy of dual advanced therapies for patients with IBD. Methods Patients at London Health Sciences Centre and St. Joseph’s Healthcare Centre on dual advanced therapies for inflammatory bowel disease were retrospectively assessed for a minimum period of 12 months. Major bacterial infection, adverse events, endoscopic, histologic, and clinical remission of IBD, and remission of EIMs of IBD were assessed. Results Five patients with Crohn’s disease receiving dual advanced therapies were identified. Stricturing Crohn’s disease was the predominant phenotype in 80% of the patients. One patient had perianal fistulizing disease. Dual therapy was initiated for concurrent management of EIMs in 80% of patients (enteropathic arthritis in 2 patients, spondyloarthritis in 2 patients, rheumatoid arthritis in 1 patient) and for refractory IBD in one patient. The majority of patients were on a combination of a tumour-necrosis-factor inhibitor and vedolizumab. Other advanced therapies included JAK inhibitors and ustekinumab. The patients were predominantly female (80%) and age at diagnosis was ampersand:003C50 years old in 80% of patients. No adverse events or major bacterial infections were observed during dual therapy. At the end of follow-up, all 5 patients were in clinical remission of their IBD and 4 patients demonstrated endoscopic remission. Only 60% of patients had remission of their EIMs within the follow-up period. Conclusions Our findings suggest that dual advanced therapies are safe and may represent a long-term treatment option for complicated patients with IBD. Funding Agencies None

THE IMPACT OF OBESITY ON THE PREVALENCE AND SEVERITY OF PERIANAL COMPLICATIONS OF CROHN'S DISEASE

Abstract INTRODUCTION The incidence of obesity in patients with inflammatory bowel disease (IBD) is increasing and there is limited data on the effects of obesity on disease phenotype. Several studies have investigated the association of obesity with perianal fistulizing disease with conflicting results. In this study, we aim to examine the relationship between obesity and the prevalence and severity of perianal complications in patients with Crohn’s disease (CD). METHODS We conducted a cross-sectional study of CD patients treated at a tertiary care center from 2012 to 2022. Collected data included sex, race, smoking history, family history, maximum body mass index (BMI), and Montreal classification (Table 1). Obesity was defined as maximum BMI ≥30kg/m2 and further subdivided into 5 BMI categories (Table 2). The prevalence of perianal disease was defined by a history of perianal fistula. The severity of perianal disease was measured by four variables including history of perianal fistula surgery, number of perianal surgeries, history of fecal diversion, and median time to first anal surgery. Perianal fistula surgeries included abscess incision and drainage, seton placement, fistulectomy, and/or fistulotomy. Pearson’s chi-squared test was used to compare 2 categorical variables (non-obese vs obese). Exact Cochran-Armitage trend test was used to compare 5 BMI categorical variables. A 95% confidence interval was used with an alpha of 0.5. Values of p <0.05 was considered statistically significant. Data analysis was performed using Excel. RESULTS A total of 704 patients with CD were treated. In all, 68.9% were non-obese and 31.1% were obese. Furthermore, 2.8% were underweight, 36.5% normal weight, 29.5% overweight, 17.9% obese, and 13.2% severely obese. Non-obese patients were more likely to have a family history of IBD (p=0.043). Obese patients were more likely to have extraintestinal manifestations (p=0.004) and/or be former smokers (p=0.004). There was no significant association between obesity and prevalence of perianal fistula (p=0.719), history of perianal surgery (p=0.146), history of one or more perianal surgeries (p=0.220), history of fecal diversion (p=0.705) or median time to first perianal surgery (p=0.192) (Table 1). Increasing BMI category was not associated with the prevalence of perianal fistula (p=0.944), perianal surgery (p=0.583), more than one perianal surgery (p=0.114), fecal diversion (p=0.542) or median time to first perianal surgery (p=0.486) (Table 2). DISCUSSION In conclusion, there was no significant correlation between obesity and prevalence of perianal disease. Additionally, there was no significant correlation between obesity and severity of perianal disease. The overall impact of obesity on CD complications is still unknown and warrants further investigation.

Surgical Options for the Treatment of Perianal and Anovaginal Fistulas in the Setting of Ileoanal Pouch Crohn’s Disease: Experience of a Tertiary Center

BackgroundThe leading cause of pouch failure following ileal pouch-anal anastomosis are peri-pouch fistulas and pelvic sepsis. ObjectiveDetermine the overall efficacy of current surgical therapy for the treatment of perianal and anovaginal fistulizing disease related to Crohn’s disease phenotype of the pouch. DesignRetrospective cohort study of a prospectively maintained, IRB-approved database. Settings/PatientsNinety-one (2.3%) patients of 3058 patients with an original diagnosis of ulcerative colitis who underwent proctocolectomy with ileal pouch-anal anastomosis between 2000 and 2021 at the Cleveland Clinic and underwent postoperative surgery for Crohn’s-related perianal disease. InterventionsTwo hundred thirty-one operations for perianal or anovaginal fistula(s). Main Outcome and MeasuresHealing rate of surgical therapy for peri-pouch fistulizing disease, impact of recurrent interventions on outcomes, and predictors of surgical failure. ResultsOverall mean age was 39.1 (± 11.6) years, with a BMI of 25.3 (± 6.3) kg/m2. More than half of the patients were female (n = 52, 57.1%). Sixty-three patients (69.2%) had a perianal fistula, 25 (27.5%) had an anovaginal fistula, and 3 (3.3%) patients had both. Overall success rate for healing was 59.3% (n = 54/91) at a mean follow-up of 6.4 (± 4.8) years. Seventeen (18.7%) patients underwent a concomitant diverting loop ileostomy. Among them, eight (47.0%) patients had the ileostomy closure after a mean time of 9.7 (± 2.8) months. In the multivariable logistic regression model, patients who had seton insertions in any operation were significantly less likely to heal (OR 0.11 95%, CI 0.03–0.43, p = 0.001). Overall pouch failure rate was 12.1%. LimitationsRetrospective single-center study which lacks a control arm and consistent long-term follow-up specific to a population-based dataset. ConclusionsPouch patients who develop perianal disease are difficult to treat, sometimes requiring pouch excision. However, when medical treatment alone is not effective, a multidisciplinary approach including surgical intervention can result in complete fistula healing in more than half of the cases.

Direct Injection of Ex Vivo Expanded Allogeneic Bone Marrow-Derived Mesenchymal Stem Cells for the Treatment of Pediatric Crohn's Perianal Fistulizing Disease.

Direct Injection of Ex Vivo Expanded Allogeneic Bone Marrow-Derived Mesenchymal Stem Cells for the Treatment of Pediatric Crohn's Perianal Fistulizing Disease.

Risk of anorectal cancer in patients with Crohn's disease and perianal fistula: a nationwide Danish cohort study.

Patients with Crohn's disease (CD) often suffer from perianal fistulizing disease. Their risk of anorectal cancer remains uncertain. We aimed to examine the long-term risk of anorectal cancer in a population-based cohort of CD patients with anorectal fistula. Our study population covered all individuals (n = 7 987 520) aged 15+ years living in Denmark from 1978 to 2018. We identified all patients with CD and anorectal fistula in the Danish National Patient Register (NPR) and 50 matched noninflammatory bowel disease (IBD) individuals from the general population. Using Cox regression analyses, we examined the risk of anorectal cancer in CD fistula patients versus non-IBD individuals. All patients with CD were identified using codes from the International Classification of Diseases and their data extracted from the NPR. The main outcome measure was cases of anorectal cancer. A total of 2786 CD patients with anorectal fistula and 139 300 non-IBD individuals were followed for 1 553 917 person-years. During follow-up, anorectal cancer was observed in 19 CD patients (0.68%) and 340 non-IBD individuals (0.24%), corresponding to a 2.9-fold increased hazard ratio (HR) of anorectal cancer in CD fistula patients (95% CI 1.80-4.53), with a particularly high risk of anal cancer (HR 15.13, 95% CI 6.88-33.31) and a mean time from CD fistula diagnosis to anorectal cancer of 6.7 (SD 6.5) years. The risk was slightly higher in women than men and had no apparent relation to treatment with tumour necrosis factor-α inhibitors. Sensitivity analyses using CD nonfistula patients for comparison revealed similar results. Individual data on smoking and infection with human papilloma virus were not available. Patients with CD and anorectal fistula have a three-fold increased risk of anorectal cancer compared with the general population. The number needed to surveil to detect one case of anorectal cancer in this patient population was 2160 patients per year in patients with long-standing fistula (>6 years).

P718 A Phase I Study of Ex Vivo Expanded Allogeneic Bone Marrow Derived Mesenchymal Stem Cells for the Treatment of Pediatric Perianal Fistulizing Crohn’s Disease

Abstract Background Background: Mesenchymal stem cells have been used for the treatment of perianal Crohn’s fistulizing disease by direction injection. However, no studies to date have included pediatric patients. Objective To determine safety and efficacy of mesenchymal stem cells for pediatric perianal fistulizing Crohn’s disease. Methods Design: Phase I safety trial Settings Tertiary inflammatory bowel disease referral center Patients Crohn’s patients aged 13-17 with perianal fistulizing disease. Intervention 75 million mesenchymal stem cells were administered with a 22G needle by direct injection after curettage and primary closure of the fistula tract. A repeat injection of 75 million mesenchymal stem cells at 3 months was given if complete clinical and radiographic healing were not achieved. Main outcomes measures Adverse and serious adverse events at post procedure day 1, week 2, week 6, month 3, month 6 and month 12. Clinical healing, radiographic healing per magnetic resonance imaging, and patient reported outcomes at the same time points. Results Results: A total of 7 pediatric patients were enrolled and treated (6 male; median age of 16.7 years). There were no adverse or serious adverse events reported related to investigational product. At six months, 83% had complete clinical and radiographic healing. The perianal Crohn’s disease activity index, Wexner incontinence score, and VanAssche score had all decreased at six months. Limitations Single institution and open label. Conclusion Bone marrow derived mesenchymal stem cells offer a safe, and likely effective, alternative treatment approach for pediatric perianal fistulizing Crohn’s disease.

S1016 Inflammatory Bowel Disease Superimposed on HIV Infection: A Mirror Image of the Remission Hypothesis?

Introduction: The intestinal epithelium is the interface between a sterile internal environment and a contaminated external environment. The conflicting needs for intimate contact to facilitate solute and water absorption while protecting against microbial invasion requires a complex defense to distinguish pathogen from non-pathogen and limit the scope and intensity of the inflammatory response. Untreated HIV infection and IBD exist at opposite ends of a spectrum, immune deficiency vs immune hyperactivity, but may coexist. In the past, IBD typically preceded HIV infection and immune depletion often was accompanied by remission of the GI disease, which led to the “Remission hypothesis”. In the current era, HIV infection often precedes the development of IBD. It is unclear if the sequence in which the two diseases develop affects their clinical course. Methods: Chart review of patients with coexisting HIV infection and IBD was performed; clinical and laboratory findings of 7 patients with IBD superimposed on HIV infection were reviewed. Results: Five patients were African American, one was Caucasian, and one was of mixed race; five were men and two were women. All patients had colonic involvement and one also had small intestinal disease. Endoscopic and histologic features were more typical of Crohn’s disease than of ulcerative colitis. Five patients presented with severe, complex perianal fistulous disease. One patient had a history of hidradenitis suppurativa and three had aseptic necrosis of the femoral heads on or prior to presentation. All seven subjects had stable HIV infection, with undetectable plasma HIV RNA and CD4 counts great than 400 cells/mm3 at diagnosis. No one had ever had a serious opportunistic infection. Four patients responded well to biologic agents, one responded to corticosteroids, and two have recently been initiated on therapy. Conclusion: These data suggest that the sequence of developing HIV infection and IBD may influence the clinical course. While progressive immune depletion in HIV infection may diminish the clinical severity of established IBD, its de novo development in an HIV-infected patient may lead to serious disease with significant disease-related morbidity. We hypothesize that the development of IBD in an HIV-infected patient may be a mirror image of the remission hypothesis; prospective studies are needed for confirmation.

A28 RESPONSE RATE OF VERY EARLY ONSET INFLAMMATORY BOWEL DISEASE (VEOIBD) PATIENTS TO ANTI-TNF TREATMENT IS HIGHER THAN PREVIOUSLY REPORTED, BUT HIGHER DOSING IS REQUIRED-A LARGE TERTIARY SINGLE CENTER EXPERIENCE

BackgroundVery early onset inflammatory bowel disease (VEOIBD) patients are known to have special disease characteristics. Limited data is available regarding biologic use and long-term outcomes in VEOIBD patients.AimsWe aimed to assess long-term outcomes and time to progression to biologic treatment in VEOIBD patients. Secondary aim was to determine Infliximab prescribing practice during the course of treatment.MethodsWe retrospectively reviewed IBD patients diagnosed under 6 years of age, between January 2005 and December 2019, from the British Columbia (BC) Pediatric IBD database. Demographic data, disease characteristics, symptoms at diagnosis, disease location and severity were documented. Data on biologic treatment at initiation and during follow up including type of biologic, dosing and response were collected. Kaplan Meier curves were used to assess the number of years to progression to biologic treatment and the parameters influencing commencement. Infliximab dosing and intervals were recorded for all patients treated with Infliximab during induction, after one year and at last follow up.Results89 patients with VEOIBD were diagnosed during the study period. Median age at diagnosis was 3.8 years (IQR 2.6–5.1), 45.3% had Crohn’s disease (CD) and 62.8% were males. Median duration of follow up was 6.39 years (IQR 3.71–10.55). Biologic treatment was started on 39.5% of patients and 7.1% underwent surgery. In patients with CD, the addition of perianal fistulizing disease or stricturing disease was associated with more rapid progression to biologic treatment (p=0.024, p=0.038, respectively). In patients with UC, disease severity (p=0.017) was associated with early initiation of a biologic. The median Infliximab dose at one year was 10 mg/kg (IQR 7.5–11) with median dose interval of 4 weeks (IQR 4–6). At the time of the last follow up, 18 patients (72%) maintained treated with Infliximab and had a median dose of 9 mg/kg per dose (IQR 8.1–10) and a median dose interval of 4.5 weeks (IQR 4–6). Clinical remission was reported in 61.8% of patients on their first biologic agent at the last follow up.ConclusionsFactors influencing earlier progression to biologics were disease severity and disease behaviour. The response rate was higher than previously reported and might be due to higher Infliximab dosing with shorter infusion intervals than standard dosing.Funding AgenciesNone

OP20 Perianal fistulas are characterised by expansion of interleukin-22 producing invariant natural killer T-cells and CD4+ T-cells which drive dysregulation of the extracellular matrix

Abstract Background Perianal fistulas are a common complication of Crohn’s disease (CD) affecting approximately 25% of patients, often predicting a more complicated disease course. Dysregulated immune responses and epithelial-to-mesenchymal transition (EMT) are hypothesised to contribute to fistulizing disease; however, they have been poorly studied. In this study, we investigated the immune phenotype of patients with perianal fistulizing disease and its relationship with tissue remodelling. Methods Immune cells were isolated from fistula curettage samples (n=31) and paired peripheral blood from patients with perianal Crohn’s (pCD) or idiopathic fistulizing disease. Multiparameter flow cytometry was performed to evaluate lymphocyte populations including invariant natural killer T-cells (iNKTs), gamma-delta (γδ) T-cells, CD161+ mucosal-associated invariant T-cells (MAIT), CD4+ T-cells and CD8+ T-cells. Gene expression profiling of fistula (Crohn’s n=11, idiopathic n=11) and rectal tissue (Crohn’s n=9, idiopathic n=9) was performed by RNA-sequencing. Cellular deconvolution of transcriptomic data using CIBERSORTx was performed to define the cellular phenotype of perianal fistulas. Cytokine treated intestinal epithelial organoids were used to probe the impact of selective cytokines on disease relevant pathways in perianal fistulas, using gene-set enrichment analysis (GSEA). Results Perianal fistulas were characterised by expansion of iNKTs and CD4+ T-cells when compared to peripheral blood. Deeper analysis of the phenotype of these populations revealed enrichment of CD8- CD4- CD161+ iNKTs producing interleukin-22 (IL22), and CD4+ CD161+ T-cells producing interleukin-13 (IL13) and IL22. Surprisingly, pCD and idiopathic fistulas displayed similar immunophenotypes. Fistulas exhibited distinct transcriptional profiles to rectal tissue, although the phenotype of pCD and idiopathic fistulas appeared similar. Pathways related to the extracellular matrix (ECM) and EMT were more activated in fistulas compared to rectum. Gene-set enrichment analysis and cellular deconvolution identified an increase in the abundance of iNKTs, activated memory CD4+ T-cells, activated NK cells and neutrophils in fistula versus rectal tissue. IL13, IL22 and TNFα responsive transcripts were enriched in fistula tissue, and in the case of IL22, was shown to regulate key matrisome components. Conclusion Perianal fistulas are characterised by increased infiltration of CD161+ iNKT cells and CD4+ T-cells, producing IL22 and IL13. These pro-inflammatory cytokines are likely important drivers of ECM dysregulation and tissue remodelling in perianal fistulizing disease.

A Multi-Disciplinary Approach to Perianal Fistulizing Crohn's Disease.

Perianal fistulizing Crohn's disease represents a severe phenotype associated with significant morbidity. Patients with perianal fistulizing disease are more likely to have a severe disease course and have significant reductions in quality of life. Moreover, these patients are at risk for the development of distal rectal and anal cancers. Given the complexity and severity of this patient group, the management of perianal Crohn's disease must be undertaken by a multidisciplinary team. The gastroenterologist and colorectal surgeon play a critical role in the diagnosis and management of perianal fistulizing disease. An examination under anesthesia provides critical information and is an essential part of the work-up of complex perianal fistulas. The radiologist also plays a central role in characterizing anatomy and assessing response to treatment. Several imaging modalities are available for these patients with magnetic resonance imaging as the imaging modality of choice. Perianal disease developing after ileal pouch-anal anastomosis represents a particularly challenging form of fistulizing disease and requires a multidisciplinary clinical and radiologic approach to differentiate surgical complications from recurrent Crohn's disease.

The Phenotypic Spectrum of New-onset IBD in Canadian Children of South Asian Ethnicity: A Prospective Multi-Centre Comparative Study.

Canadian-born children of South Asian [SA] ethnicity develop inflammatory bowel disease [IBD] at similar rates to those among Caucasian children. We evaluated the variation in phenotypic spectrum of IBD in SA and Caucasian children in a national paediatric inception cohort of new-onset IBD. Patients aged <17 years, enrolled in a Canadian nationwide inception cohort study, were included. Baseline demographic and IBD phenotypic features were compared between SA and Caucasian children. Longitudinal outcomes through 18 months of follow-up were compared matched by propensity scores. Of 1156 children enrolled over 2014 to 2019, 623 were Caucasian [98% and 88% parents Canadian born] and 114 SA [79% Canadian born, 87% parents SA born]. Fewer SAs have a first-degree relative with IBD, 6% vs 19% in Caucasians, p = 0.002. SAs present at a younger age, median age 11.4 years (interquartile range [IQR] 9.2-14.3) vs 13 years [IQR 10.9-15 years], p = 0.03 and more commonly with a UC/IBD-U [ulcerative colitis/IBD-unclassified] subtype [ratio of UC/IBD-U to CD 1.2:1 vs 1:1.8 for Caucasians, p <0.001]. Additionally, a greater proportion of SA CD patients present with colonic-only disease [colonic-only CD/UC/IBD-U in SAs 67% vs 57% for Caucasians, p = 0.001], and among those with CD, colonic CD in SAs 31% vs 23% in Caucasians, p = 0.20]. Perianal fistulising disease was also numerically more common in SAs (14 [27%] vs 64 [18%], p = 0.06]. Adjusting for differences in phenotypic presentation, anti-tumour necrosis factor [TNF] exposure, and time to initiation was similar, and two-thirds of children, whether anti-TNF exposed or naïve, were in corticosteroid-free clinical remission at 18 months irrespective of ethnicity. The phenotypic spectrum of new-onset IBD in SA children differs from that of Caucasian children, but treatment and clinical course are similar within phenotypic subgroups.

Managing Complex Perianal Fistulizing Disease.

Perianal disease is a particularly morbid phenotype of Crohn's disease, affecting up to one third of patients, with a significantly diminished quality of life. Conventional medical therapy and surgical interventions have limited efficacy. Medical treatment options achieve long-term durable remission in only a third of patients. Therefore, most patients undergo an operation, leaving them with a chronic seton or at risk of incontinence with multiple interventions. Mesenchymal stem cell therapy is an emerging therapy without risk of incontinence and improved efficacy as compared with conventional therapy. Laser therapy is another new intervention. Unfortunately, up to 40% of patients still require a stoma related to perianal fistulizing disease.

P280 Introduction of subcutaneous infliximab CT-P13 and vedolizumab in daily clinical practice: outstanding questions demonstrate the need for post-marketing studies

Abstract Background Although clinical trials led to the registration of subcutaneous (SC) infliximab CT-P13 (IFX) and SC vedolizumab (VDZ) for patients with Crohn’s disease (CD) and ulcerative colitis (UC), many practical aspects have not been addressed yet. We explored what strategy Belgian clinicians plan to follow once these formulations become available. Methods A 3-round Delphi process was initiated in Jan 2021. A core panel (4 IBD clinicians, 1 PKPD expert, 1 IBD nurse, 1 methodologist) developed a neutral video on the available data, as well as 65 statements and 9 multiple-choice questions related to the practical use of SC IFX and VDZ. The expert panel, consisting of 45 IBD clinicians (median [IQR] years of practice 19 [11-26] years), scored all statements on a 10-point Likert scale. We here present the results of the first Delphi round. The complete report will be available after the final Delphi round in May 2021. A ≥70% consensus level (scores 1-4 for disagreement, scores 7-10 for agreement) is foreseen. Results The majority of IBD clinicians expressed the need for more scientific data on switching from intravenous (IV) to SC therapy (Table 1). Furthermore, a minority would consider starting SC therapy after only two IV induction doses (Figure 1). Most clinicians would restrict switching to patients who achieved both clinical, biological response, and endoscopic response (Figure 2) and this only when receiving standard IV dosing of 5mg/kg IFX (75.5%) or 300mg VDZ every 8 weeks (68.9%). Both for IFX and VDZ, 57.1% of IBD clinicians would administer a first SC dose no later than 6 weeks after the last IV administration. The IBD clinicians highlighted the role of the IBD nurse in explaining and guiding a potential switch (82.2% IFX, 88.9% VDZ) and supervising the first SC administration (100.0% IFX, 95.5% VDZ). They emphasized the need for a clinical follow-up within 8 weeks (88.6% IFX, 88.9% VDZ). Although reactive therapeutic drug monitoring under SC therapy was considered helpful by IBD clinicians (77.8% IFX, 68.9% VDZ), they acknowledged the lack of an optimal serum concentration (73.4% IFX, 84.3% VDZ). Round one did not result in a consensus on using SC formulations in patients with quiescent perianal fistulising disease or a prior episode of acute severe UC. Finally, the optimal strategy in case of an objectified clinical relapse after switching to SC therapy seems is clearly unknown (83.3% IFX, 76.2% VDZ). Conclusion Although both SC IFX and SC VDZ will become available soon, the majority of IBD clinicians expressed the need for more scientific data on switching from IV to SC therapy. This Delphi process may indicate pivotal remaining research questions to be answered through post-marketing studies.

MRI of Perianal Crohn Disease: Technique and Interpretation.

Magnetic resonance imaging (MRI) has emerged as the imaging method of choice for evaluation of perianal fistulizing disease. As treatment of Crohn disease and associated perianal fistulas has evolved to include a combination of systemic treatments and surgical interventions, perianal MRI provides critical information to guide treatment selection and timing. Radiologists need to be familiar with the normal regional anatomy to accurately describe perianal fistulas and any associated complications which can then be used to classify fistulas based on several available classification systems. Following treatment, MRI can provide information that suggests treatment success or failure. We propose a perianal fistula reporting template that includes the necessary information to convey fistula complexity, guide treatment, and evaluate treatment response. This review article will also discuss the postoperative appearance of many treatments currently used for management of perianal fistulizing disease and some associated complications.

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.

Modern surgical strategies for perianal Crohn's disease

One of the most challenging phenotypes of Crohn’s disease is perianal fistulizing disease (PFCD). It occurs in up to 50% of the patients who also have symptoms in other parts of the gastrointestinal tract, and in 5% of the cases it occurs as the first manifestation. It is associated with severe symptoms, such as pain, fecal incontinence, and a significant reduction in quality of life. The presence of perianal disease in conjunction with Crohn’s disease portends a significantly worse disease course. These patients require close monitoring to identify those at risk of worsening disease, suboptimal biological drug levels, and signs of developing neoplasm. The last 2 decades have seen significant advancements in the management of PFCD. More recently, newer biologics, cell-based therapies, and novel surgical techniques have been introduced in the hope of improved outcomes. However, in refractory cases, many patients face the decision of having a stoma made and/or a proctectomy performed. In this review, we describe modern surgical management and the most recent advances in the management of complex PFCD, which will likely impact clinical practice.

Management of Isolated Anal Strictures in Crohn's Disease.

Anorectal stricturing is a particularly morbid manifestation of Crohn's disease resulting in a diminished quality of life related to pain, incontinence, and recurrent operative interventions. To determine the role of medical therapy, endoscopic dilation, and surgical intervention for the treatment of isolated anorectal stricturing. An organized search of MEDLINE, PubMed, EMBASE, Scopus, and the Cochrane Database of Collected Reviews was performed from January 1, 1990 through May 1, 2020. Full text papers which included management of isolated anorectal strictures in the setting of Crohn's disease. Medical and surgical management. Symptomatic relief, need for proctocolectomy. Our search identified a total of 553 papers; after exclusion based on title (n = 430) and abstract (n = 47), 76 underwent full text review with 65 relevant to the management of anorectal strictures. A summary of the retrospective reports suggests that medical therapy can help control luminal inflammation, but fibrosis may ultimately set in resulting in a need for endoscopic or surgical intervention. Surgical options are limited in the anal canal due to inflammation and ulceration and concomitant perianal fistulizing disease. While fecal diversion can provide symptomatic relief, successful restoration of intestinal continuity remains uncommon and most patients ultimately undergo a total proctocolectomy with end ileostomy. Limited literature published, all retrospective in nature. Despite significant advances in medical and surgical therapy in Crohn's disease over the last decades, there is clearly an unmet need in the management of anorectal strictures in Crohn's disease.

Pancytopenia in a Young Male Patient With Inflammatory Bowel Disease

Question: A 20-year-old male college student with a history of Crohn’s disease was noted to have pancytopenia on routine lab monitoring. He was diagnosed with stricturing Crohn’s disease of the terminal ileum and colon over 10 years ago when he presented with weight loss and bloody diarrhea. He struggled with perianal fistulizing disease periodically. His Montreal classification was A1 L3 B2p. Previous therapies included corticosteroids, mesalamine, azathioprine, 6-MP, infliximab, adalimumab, methotrexate, and certolizumab often in combination.