Perianal Fistulas In Crohn's Disease Research Articles

Granulomas without foreign body giant cells in perianal fistula tissue suggest Crohn's disease.

Histopathological characteristics of granulomas in perianal fistula of patients with Crohn's disease (CD) remain unexplored. We aimed to assess the histopathological features of granulomas in perianal fistula in CD. A retrospective analysis was conducted by reviewing the medical and pathological records of 4430 cases who underwent perianal fistulectomy at our hospital between June 2015 and June 2023. The patients were divided into the CD group, tuberculosis (TB), and non-CD group, respectively, based on their final diangosis. The detection rate of granulomas and differential histopathological features were investigated. Among the 4430 patients, granulomas were identified in 41 cases, including 25 had CD, 2 had pulmonary TB, and 14 only exhibiting perianal lesions with no other comorbidities. Additionally, there were altogether 93 CD cases, resulting in a detection rate of granuloma of 26.9%, which was considerably higher than that in the non-CD group (26.9% vs 0.3%, p < 0.001). The majority (85.7%) of the perianal fistula tissues in the non-CD group contained foreign body giant cells, while this was observed in only 1 (4.0%) out of the 25 cases with CD. We proposed that granulomas in the perianal fistula in the non-CD group were mostly foreign body granulomas. Moreover, granulomas in the non-CD group were larger than that of the CD group (1135 μm vs 519 μm, p < 0.001). Most CD cases have less granulomas (≤3) and no foreign body giant cells. Ribbon-like granulomas can be seen only in CD cases.

Localized Administration of Mesenchymal Stem Cell-Derived Exosomes for the Treatment of Refractory Perianal Fistula in Crohn's Disease Patients: A Phase II Clinical Trial.

Crohn's disease perianal fistulae are often resistant to standard anti-TNF-α therapies. Mesenchymal stem cell (MSC)-derived exosomes are extracellular vesicles that have highly potent anti-inflammatory effects, and the previous phase of this study demonstrated their safety in the treatment of refractory perianal fistulas. To evaluate the efficacy of mesenchymal stem cell-derived exosomes for the treatment of refractory perianal fistulas. Nonrandomized, nonblinded single-center phase II clinical trial. Tertiary university hospital. Twenty-three patients were enrolled, 20 of whom completed the study. Refractory perianal fistula was defined as resistance to at least one course of treatment with anti-tumor necrosis facto-α therapy. After clinical assessment and magnetic resonance imaging, the patients were subjected to general anesthesia, and 5 mL of exosome solution was injected directly into the fistula tracts. The injections were repeated three times at 2-month intervals, and patients were followed monthly for 6 months after the last injection. Tissue samples from the tracts were obtained before each injection and subjected to immunohistopathological assessment. MRI data were obtained before and six months after the last injection. The primary outcome of this study was fistula tract closure on clinical examination and magnetic resonance imaging. The secondary outcome was an improvement in the discharge from the tracts. Fistula tracts were fully closed in 12 (60%) of the patients. Four patients showed clinical improvement, with some tracts remaining open, and four patients were completely resistant to treatment. A total of 43 fistula tracts were treated during the trial, 30 (69.7%) of which showed complete closure. Histopathological analysis revealed substantial reductions in local inflammation and signs of enhanced tissue regeneration. Immunohistochemical analysis of cluster of differentiation-68, 20 and 31 reaffirmed these results. MSC-derived exosomes are safe and effective for treating refractory perianal fistulas in patients with Crohn's disease. See Video Abstract.

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

Crohn's disease (CD) is a chronic and relapsing inflammatory bowel disease affecting the entire gastrointestinal tract. The prevalence of CD among Japanese people is increasing. One of the most frequent complications of CD is perianal fistulas. People living with CD may experience complex perianal fistulas, which can cause intense pain, bleeding, swelling, infection, and anal discharge. Despite medical and surgical advancements, complex perianal fistulas in CD remain challenging for clinicians to treat. CD patients living with perianal fistulas reported a negative impact on many aspects of their quality of life. Darvadstrocel is a cell therapy product containing a suspension of allogeneic expanded adipose-derived mesenchymal stem cells. It has been approved in Europe and Japan for the treatment of complex perianal fistulas that have shown an inadequate response to at least one conventional or biologic therapy in adult patients with non-active/mildly active luminal CD. By exhibiting immunomodulatory and local anti-inflammatory effects at the site of inflammation, it offers a new treatment option for complex perianal fistulas in CD patients. In this manuscript, the characteristic of darvadstrocel, the summary of results from the pivotal phase 3 studies in Europe and Japan, and the development strategy in Japan were introduced.

Clinical and magnetic resonance imaging spectrum of complex perianal fistulizing Crohn's disease: A cohort study from northern India.

Fistulizing perianal Crohn's disease (CD) is a debilitating condition associated with significant morbidity and reduction in thequality of life. Magnetic resonance imaging (MRI) of the pelvis is the preferred imaging modality for thecomprehensive assessment of the perianal fistula. There is apaucity of data from India on the MRI spectrum of complex perianal fistula in CD. A single-centre cross-sectional analysis of patients with fistulizing perianal CD, who underwent pelvic MRI between January 2020 and December 2021, was performed. The clinical (age, sex, disease duration, disease location and behavior, disease activity [Perianal Disease Activity Index, PDAI] and treatment received) and radiological (number and location of fistulae, extensions, number and location of internal and external openings, fistula activity, presence or absence of perianal abscess and associated proctitis) characteristics of complex perianal fistula (defined according to the American Gastroenterological Association classification) were recorded. Of total 175 patients with CD who attended the gastroenterology clinic during the study period, 27 (15.42%) (mean age 42±15.5 years, 62.96% females and median disease duration four years) had complex perianal fistula and were included in the analysis. The mean PDAI was 5.48±2.53. The median Van Assche Index was 17 (interquartile range [IQR] 13-19). A majority (96.29%) of the fistulae were trans-sphincteric and four (14.81%) fistulae extended into the supralevator space. All fistulae were active on MRI. Concomitant perianal abscess and proctitis were seen in 59.26% (n=16) and 62.96% (n=17) of patients, respectively. Combination therapy with biologics and antibiotics/immune-suppressants were the most commonly prescribed medical therapy. Six (22.22%) patients underwent combined medical and surgical (non-cutting seton, fistulectomy, fecal diversion) treatment. The cumulative risk of thedevelopment of fistulizing perianal CD in a northern Indian cohort was similar to the western populations. Complex perianal fistulae were predominantly trans-sphincteric and commoner in females. MRI evaluation is pivotal forthe delineation of fistula anatomy, assessment of disease extent and activity and theevaluation of concomitant perianal abscess and other complications.

Superior Efficacy of Infliximab Versus Adalimumab for First-Line Treatment of Crohn's Perianal Fistulae.

Crohn's disease perianal fistulae (CD-PAF) occur in 25% of patients and are notoriously challenging to manage. Tumor necrosis factor inhibitors are first line agents. The aim of this study was to compare infliximab (IFX) versus adalimumab (ADA) efficacy in CD-PAF healing over time. A retrospective study at two large-tertiary medical centers was performed. Inclusion criteria were actively draining CD-PAF and initial treatment with IFX or ADA following CD-PAF diagnosis. The primary endpoints were perianal fistula response and remission at 6 and 12months. Secondary endpoints included biologic persistence over time and dose escalation at 6 and 12months. Among 151 patients included in the study, 92 received IFX and 59 received ADA as first line agents after CD-PAF diagnosis. At 6months, the 64.9% of the IFX group and 34.8% of the ADA group demonstrated CD-PAF clinical improvement (p < 0.01). Univariate and multivariate analyses demonstrated significant differences among the IFX and ADA groups for clinical response at 6-months and 12-months (p = 0.002 and p = 0.042, respectively). There were no factors that predicted response, with the exception of concomitant immunomodulator affecting the 6-month clinical response (p = 0.021). Biologic persistence, characterized by Kaplan Meier methods, was significantly longer in the IFX group compared to the ADA group (Log-rank p = 0.01). IFX induction and maintenance is associated with higher rates of response and remission in CD-PAF healing as well as higher treatment persistence compared to ADA. Additionally, our study supports the use of concomitant immunomodulator therapy for CD-PAF healing and remission.

Malignancy rates in Crohn's disease patients with perianal fistula: A German retrospective cohort study.

Patients with inflammatory bowel disease are at increased risk of colorectal and extra-intestinal cancer. However, the overall cancer risk in patients with Crohn's disease (CD) with perianal fistulas (PF) (CPF) and those with CD without PF (non-PF CD) is unclear. To describe the prevalence and incidence of cancer in patients with CPF and non-PF CD, and to estimate incidence rate ratio (IRR) of cancer between CPF and non-PF CD groups. A retrospective cohort study was conducted using the German InGef (Institute for Applied Health Research Berlin) research database. Patients with a CD record and PF from 1 January 2013 to 31 December 2014 were identified and followed up from 1 January 2015 until the first occurrence of cancer, end of health insurance contributing data, death, or end of study period (31 December 2020). Prevalence of any type of cancer including patients with CD diagnosed with cancer in the selection period and incidence of cancer excluding patients with CD diagnosed with cancer in the selection period were calculated. In total, 10,208 patients with CD were identified. Of 824 patients with CPF (8.1%), 67 had had a malignancy (6-year period crude malignancy prevalence 8.13% [95% confidence interval (CI) 6.36%-10.21%]), which was lower than patients with non-PF CD (19.8% [95% CI 19%-20.6%]). Incidence (per 100,000 person-years) in patients with CPF was 1184 (95% CI 879-1561) and in non-PF CD was 2365 (95% CI 2219-2519). There was no significant difference in the adjusted IRR of cancer for the CPF group compared with the non-PF CD group (0.83 [95% CI 0.62-1.10]; p=0.219). There was no significant difference in the incidence of any cancer in patients with CPF compared with non-PF CD. However, patients with CPF had a higher numerical risk of cancer than the general German population.

Approaches in the treatment of perianal fistula in Crohn disease

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

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

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

Short-term anti-TNF therapy with surgical closure versus anti-TNF therapy in the treatment of perianal fistulas in Crohn's disease (PISA-II): a patient preference randomised trial

Guidelines on Crohn's perianal fistulas recommend anti-tumour necrosis factor (TNF) treatment and suggest considering surgical closure for patients with surgically amenable disease. However, long-term outcomes following these two strategies have not been directly compared. The aim of this study was to assess radiological healing in patients who received short-term anti-TNF treatment and surgical closure compared with those who received anti-TNF treatment alone. The PISA-II trial was a multicentre, patient preference study done in nine hospitals in the Netherlands and one hospital in Italy. Adult patients with Crohn's disease and an active high perianal fistula with a single internal opening were eligible for inclusion. After counselling, patients with no treatment preference were randomly assigned (1:1) using random block randomisation (block sizes of six without statification), to 4-month anti-TNF therapy and surgical closure or anti-TNF therapy for 1 year, after seton insertion. Patients with a treatment preference received their preferred therapy. The primary outcome was radiological healing assessed by MRI at 18 months, defined as a complete fibrotic tract or a MAGNIFI-CD (Magnetic Resonance Index for Fistula Imaging in Crohn's Disease) score of 0, assessed according to the intention-to-treat principle. Secondary outcomes included clinical closure, number of patients undergoing surgical reintervention and number of reinterventions, recurrences, and impact on quality of life measured by the Perianal Disease Activity Index (PDAI). Analyses were performed on an intention-to-treat basis and additionally an as-treated analysis for radiological healing and clinical closure. This study was registered at the Dutch Trial Registry, NL7625, and with EudraCT, 2018-002064-15, and is closed to accrual due to completion. Between Sept 14, 2013, and Dec 7, 2019, 94 patients were enrolled onto the trial, of whom 32 (34%) were randomly assigned and 62 (66%) chose a specific treatment. 38 (40%) patients were assigned to the surgical closure group and 56 (60%) patients to the anti-TNF group. At 18 months, radiological healing was significantly more common in the surgical closure group (12 [32%] patients) than in the anti-TNF group (five [9%] patients; p=0·005). By contrast, clinical closure was not significantly different between the two treatment groups (26 [68%] patients in the surgical closure group vs 29 [52%] patients in the anti-TNF group; p=0·076). Significantly fewer patients required a reintervention in the surgical closure group than in the anti-TNF therapy group (five [13%] patients in the surgical closure group, median one reintervention [IQR one to three] vs 24 [43%] patients in the anti-TNF group, median two reinterventions [one to two]; p=0·005). Among patients who reached clinical closure during follow-up, four (14%) of 29 in the surgical closure group and five (16%) of 31 in the anti-TNF therapy group had a recurrence, which occurred only in patients without radiological healing. PDAI was significantly lower in the surgical closure group than in the anti-TNF group after 18 months (p=0·031). Adverse events and serious adverse events were similar in both treatment groups and mostly entailed reinterventions. Ten (11%) patients had side-effects associated with anti-TNF treatment. Two serious adverse events unrelated to study treatment occurred (appendicitis and myocardial infarction). One patient died from a tongue base carcinoma, unrelated to study treatment. Short-term anti-TNF treatment combined with surgical closure induces long-term MRI healing more frequently than anti-TNF therapy in patients with Crohn's perianal fistulas. These data suggest that patients with Crohn's perianal fistula amenable for surgical closure should be counselled for this therapeutic approach. Netherlands Organisation for Health Research and Development and Broad Medical Research Program.

Epidemiology and diagnosis of inflammatory bowel diseases

Background: Over the past three decades, inflammatory bowel diseases (IBD) have been rapidly increasing in the African, South American, and Asian countries, including Korea. However, in Korea, the public awareness of IBD remains low, and diagnostic delay is not uncommon due to the physicians' lack of clinical experience. It is essential to understand the trends and regional differences in the epidemiology of IBD for proper diagnosis and treatment.Current Concepts: Although lower than those of the West, the prevalence and incidence of IBD in Korea rank among the highest in Asia and are steadily increasing. In the past 10 years, the prevalence of IBD has almost doubled, while its incidence has decreased gradually. As compared to Western IBD patients, Korean patients have higher proportion of proctitis in ulcerative colitis, male predominance, more ileocolonic involvement, and higher incidence of perianal fistula in Crohn disease. There is no single gold standard for the diagnosis of IBD. Thus, diagnosis can be made by clinical evaluation, including a detailed history taking, physical examination, and a combination of endoscopic, radiologic, laboratory, and histologic findings.Discussion and Conclusion: Population-based studies have revealed the current trends and characteristics of the epidemiology of IBD in Korea. Continued education and development of diagnostic tools will help clinicians to diagnose IBD accurately and differentiate it from other diseases such as intestinal tuberculosis.

Statement of the polish expert group on the current practice and prospects for the treatment of complex perianal fistulas in Crohn&apos;s disease. Update 2021.

Perianal fistulas in Crohn's disease (CD) are a major problem. In majority of patient, inflammation involves the rectum. Perianal fistulas in CD pose a diagnostic and therapeutic challenge due to severe symptoms and worse prognosis compared to cryptogenic fistulas. The accurate diagnosis is crucial for an effective treatment of CD-related perianal fistulas, and the following should be determined: anatomy of the fistula, possible strictures and inflammation of the alimentary tract, including the rectum and the anal canal. Treatment of fistulas might be challenging and requires cooperation between the colorectal surgeon and the gastroenterologist. The combination of surgical and pharmacological therapy is more effective than surgical or pharmacological therapy alone. In conservative treatment, aminosalicylates or steroids have little significance. In everyday practice, antibacterial chemotherapeutics, antibiotics and thiopurines are applied. The most effective are TNF-neutralizing antibodies, i.e. infliximab (IFX), adalimumab (ADA) and certolizumab (CER). Surgical management can be urgent including drainage. Elective procedures include dissection of the fistula (simple fistula) or more complex interventions such as mucosal flap or ligation of the intersphincteric portion of the fistula. Surgical interventions can be enhanced using the video-assisted anal fistula treatment (VAAFT) or negative-pressure therapy. In extreme cases, creation of a stoma may be necessary. Also, tissue glues or so-called plugs may be applied in managing perianal fistulas. The use of stem cells seems promising, i.e. application of multipotent non-hematopoietic stem cells around the fistula in order to induce immunomodulation and wound healing.

MRI of perianal fistulas in Crohn's disease.

Perianal fistulas represent one of the most critical complications of Crohn’s disease (CD). Management and treatment need a multidisciplinary approach with an accurate description of imaging findings.Aim.This study aspires to assess the significative role of Magnetic Resonance Imaging (MRI) in the study of perianal fistulas, secondary extensions, and abscess in patients with CD. Therefore it is essential to standardize an appropriate protocol of sequences that allow the correct evaluation of disease activity and complications.Methods:We selected and reviewed ten recent studies among the most recent ones present in literature exclusively about pelvic MRI imaging and features in CD. We excluded studies that weren’t in the English language.Conclusions:MRI has a crucial role in the evaluation and detection of CD perianal fistulas because, thanks to its panoramic and multiplanar view, it gives excellent anatomic detail of the anal sphincters. Today MRI is the gold standard imaging technique for the evaluation of perianal fistulas, mainly because this technique shows higher concordance with surgical findings than does any other imaging evaluation. Surgical treatment is often required in the management of perianal fistula in patients with CD, which often have complex perineal findings. (www.actabiomedica.it)

Mesenchymal stem-cell therapy for perianal fistulas in Crohn's disease: a systematic review and meta-analysis.

Mesenchymal stem-cell (MSC) therapy for perianal fistulas in Crohn's disease (CD) remains controversial. We performed this meta-analysis to evaluate the efficacy and safety of MSC therapy for the treatment of perianal fistulas in CD. Electronic databases were searched for studies that reported efficacy and/or safety of MSC therapy for perianal CD (pCD). We used the metaprop command of the meta package in R and RevMan to assess the efficacy and safety. Subgroup analyses were performed for exploration of heterogeneity regarding all outcomes. After screening, 13 trials were included in our study. RevMan for meta-analysis showed that: (1) patients had healed perianal fistulas after MSC treatment, with an odds ratio (OR) of 2.05 (P = 0.0002; 95% confidence interval (CI) 1.41, 3.00) vs controls; (2) pelvic magnetic resonance imaging (MRI) used to evaluate the healing of fistulas showed that MSC therapy had a higher healing rate (HR) compared to control (OR = 1.95; P = 0.0007; 95% CI 1.33, 2.87). R software for meta-analysis showed that 63% (95% CI 0.53, 0.74) of patients achieved clinical healing as a result of local therapy with MSCs. Random-effects pooled rates of clinical response were 30% (95% CI 0.18, 0.48). Pelvic MRI used to evaluate fistula healing showed a HR of 56% (95% CI 0.46, 0.69). The HR with autologous MSCs was higher than with allogeneic MSCs (79% vs 52%; P < 0.05). Uniform injection of MSCs according to the size of fistulas improve the HR (80% vs 55%; P < 0.05) compared with fixed-dose MSCs. There was no significant increase in adverse events (OR = 1.14; P = 0.54; 95% CI 0.75, 1.74) in patients treated with MSCs and no major MSC-related adverse event has been reported so far. Local administration of MSCs is an effective and safe method for pCD. It also represents hope for effective treatment of refractory pCD.

Elicitation of Health-Related Utility in Perianal Fistula in Crohn's Disease.

Perianal fistulae are a common complication of Crohn's disease (CD) and pose a substantial burden on quality of life. Data capturing health-related utility associated with perianal fistulae in CD are scarce. The current study aims to value health states related to different stages of the disease to quantitatively evaluate the impact of complex perianal fistulae on CD patients' quality of life. Eight health state descriptions associated with complex perianal fistulae in CD were developed following qualitative research with patients and validation by clinicians. Following pre-testing, a survey was administered online in two samples of UK respondents: the general population and patients with CD. A choice-based valuation technique, the time trade-off (TTO), was used for direct utility measurement. CD patients also valued their current health state using the TTO. Exclusion criteria for respondents displaying logical inconsistencies were applied. Usable responses were received from 835 respondents, reflective of the UK population in age and sex, in the general population survey and 162 CD patients in the patient survey. Non-remission states were valued much lower than the remission state by both samples, ranging from 0.20 for proctectomy with a negative outcome to 0.66 for chronic symptomatic fistulae with mild symptoms. Patients currently experiencing fistulae reported lower values for current health than those without fistulae. Low utility values were assigned to the non-remission health states for perianal fistulae in CD by the general public and patients with CD. This demonstrates the high humanistic burden of inadequately managed perianal fistula in CD.

Standardization of mesenchymal stromal cell therapy for perianal fistulizing Crohn's disease.

Local administration of mesenchymal stromal cells (MSCs) into the fistula tract seems to improve patient outcome in perianal fistulas due to Crohn's disease (CD). In this paper we propose a standardized and validated protocol for the local administration of MSCs for CD perianal fistulas to be able to reliably assess efficacy. A working group consisting of gastroenterologists and surgeons with expertise in the treatment of perianal CD developed a consensus perianal fistula treatment protocol for local MSC treatment of perianal fistulizing CD. The treatment protocol was validated during a trial of allogeneic bone marrow-derived MSCs for the treatment of refractory perianal Crohn's fistulas. Localization and classification of perianal fistulas with MRI and rectoscopy is of crucial importance prior to surgical intervention with local therapy administration. Examination under anesthesia is necessary to incise and drain abscesses when present. Optimization of medical treatment when active luminal CD is present, is the first step before embarking on surgery and local therapy administration. In addition, strictures preventing the surgeon from adequately performing the surgical procedure have to be endoscopically dilated. Curettage of the fistula tract has an important role as long-standing CD perianal fistulas close poorly without removal of their epithelial lining. To diminish bacterial contamination of the fistula, the internal opening has to be closed. The origin of the fistula is the internal opening, therefore, efficacy of MSCs is presumably the highest when they are injected into the tissue around the internal opening. In this article, we propose a standardized method of local MSC administration for perianal fistulizing CD. The use of this standardized and validated protocol for the administration of local treatment of CD perianal fistulas will allow reliable comparison of the efficacy of local therapies in future.

DOP059 Combined anticytokine and local mesenchymal stem cells therapy promotes longer healing of simple fistulas in patients with Crohn’s disease

Mesenchymal stromal cells (MSCs), which have immunomodulatory properties and a large regenerative potential, are now used to treat fistula in Crohn's disease (CD). Aim: compare the effectiveness of combined therapy (local and systemic administration) with bone marrow mesenchymal stromal cells (MSC), infliximab (IFX) and antibiotics (AB)/immunosuppressors (IS) on the frequency of healing of simple perianal fistulas in CD. 50 patients with CD were divided into four groups, depending on the method of therapy. The first group of patients (n = 12) received MSCs systemically and locally according to the scheme. The second group (n = 10) received therapy of IFX according to the scheme. The third group (n = 14) received AB and IS. The fourth group (n = 14) received IFX according to the scheme and local MSCs. In the dynamics the closure of the external fistula opening was evaluated at 12, 26, 52 and 104 weeks from the start of therapy. After 12 weeks among patients of the first group, healing of simple fistulas was noted in 10/12 patients (83.3%), in the second group, healing of simple fistulas was noted in 8/10 (80.0%) (RR-0.83; 95% CI 0.14–4.9, p = 0.72). In the third group, healing of simple fistulas was noted in 5/14 patients (35.7%) (RR-0.26, 95% CI 0.07–0.97, p = 0.04 compared with the first group). In the fourth group, healing of simple fistulas was noted in 13/14 patients (92.8%) (RR −0.90, 95% CI 0.67–1.2, p = 0.88 in comparison with the first group). After 26 weeks in the first group, healing of simple fistulas was preserved in 8/12 (66.6%) patients, and in the second group it was preserved in 7/10 (70.0%) patients (RR −1.11, 95% CI 0.32–3.84, p = 0.76). In the third group, in 4/14 patients (28.6%) (RR −0.47, 95% CI 0.2–1.11, p = 0.12 compared with the first group). In the fourth group, 13/14 patients (92.8%) (RR −0.72, 95% CI 0.47–1.1, p = 0.23). After 52 weeks in the first group, the healing of simple fistulas was preserved in 7/12 (58.3%), and in the second group it was preserved in 6/10 (60.0%) (RR −1.25, 95% CI 0.48–3.22, p = 0.69). In the third group, in 2/14 patients (14.3%) (RR −0.49, 95% CI 0.24–0.98, p = 0.03 compared with the first group). In the fourth group, 13/14 patients (92.8%) (RR-0.63, 95% CI 0.38–1.04, p = 0.1). In 104 weeks, among the patients of the first group, fistula closure was maintained in 5/12 patients (41.6%), in the second group in 5/10 (50.0%) (RR −1.17, 95% CI 0.53–2.55, p = 0.96). In the third group, in 0/14 patients (0.0%) (RR-0.58, 95% CI 0.36–0.94, p = 0.01 compared with the first group). In the fourth group, 13/14 patients (92.8%) (RR-0.45, 95% CI 0.23–0.89, p = 0.016 in comparison with first group; RR-0, 54, 95% CI 0.28–1.00, p = 0.05 in comparison with the second group). Combination anti-cytokine therapy and local mesenchymal stromal cells therapy contribute to the more frequent and prolonged closure of simple fistulas in patients with CD in comparison with other known therapy.

Clinical efficacy of adalimumab versus infliximab and the factors associated with recurrence or aggravation during treatment of anal fistulas in Crohn's disease

Background/AimsInfliximab has proven to be effective in the treatment of perianal fistulas in Crohn's disease (CD) but the efficacy of adalimumab is still unclear. The aim of this study is to assess the clinical efficacy of adalimumab and compare the results with those for infliximab.MethodsForty-seven CD patients treated for perianal fistulas with infliximab from September 2005 to December 2010 (n=31), or with adalimumab from November 2010 to May 2012 (n=16), were enrolled in this retrospective study. The following patient characteristics were analyzed; intestinal lesion site, fistula classification, seton placement, index of inflammatory bowel disease, C-reactive protein level, follow-up period, and the cumulative rate of nonrecurrence or aggravation of fistula.ResultsThere were no significant differences in the intestinal lesion site, fistula classification, inflammatory bowel disease index, C-reactive protein level, and the frequency of injection between the infliximab group and the adalimumab group. The cumulative rate of nonrecurrence or aggravation of fistula was 62.5% in the adalimumab group and 83.9% in the infliximab group at 24 months after treatment (P=0.09). The risk factors for recurrence or aggravation may be related to seton placement (P=0.02), gender (P=0.06), and fistula classification (P=0.07).ConclusionsThere was no significant difference in the clinical efficacy of adalimumab and infliximab in the treatment of perianal fistulas in CD. However, fistula classification may be an important risk factor for recurrence or aggravation. The preliminary findings in this study show that further research is warranted.

Magnetization transfer ratio for the assessment of perianal fistula activity in Crohn's disease.

Assessment of perianal fistulas is important to guide management of Crohn's disease (CD). Our objectives were to analyze the feasibility of magnetization transfer (MT) imaging to assess fistulas and to evaluate its contribution in assessing disease activity. During 15 months, all patients referred for perianal fistulas in CD underwent 3T-MRI including diffusion, T2/T1-weighted gadolinium-enhanced sequences and MT sequences (one with an off-resonance saturation pulse of 800 and one with 1200 Hz). We collected Van Assche score, fistula activity signs by analyzing T2, diffusion and contrast enhancement. We calculated MT ratio (MTR) with a ROI in the largest fistula. Twenty-nine patients (mean 34.9 years, range 17-53) were included. Van Assche score was 11.7, range 4-21. In 22 patients, the fistula presented with a bright T2 and diffusion signal with contrast enhancement, and was characterized as active. Mean MTR was respectively 47.2 (range 12-68) and 34.3 (range 11-57) at 800 and 1200 Hz. MTR at 800 Hz was significantly lower in non-active (34, range 12-55) than in active fistulas (51, range 24-68) (p < 0.02). MTR is feasible for the assessment of fistulas in CD and in the future could be used to help identify active and non-active fistulas. • MTR is feasible for the assessment of perianal fistulas in CD. • MT allows quantitative imaging of perianal fistula activity in CD. • MTR could be used to help identify active and non-active fistulas in CD.

Use of Endoscopic Ultrasound to Guide Adalimumab Treatment in Perianal Crohn's Disease Results in Faster Fistula Healing.

Perianal disease is a manifestation of Crohn's disease (CD) that has poor long-term treatment outcomes. The aim was to determine if rectal endoscopic ultrasound (EUS)-guided therapy with adalimumab (ADA) can improve outcomes for patients with perianal fistulizing CD. This is a randomized prospective study comparing serial EUS guidance of fistula treatment versus standard of care in fistulizing perianal CD. At enrollment, all patients underwent a rectal EUS and an EUA with seton placement and/or I&D. Treatment was maximized with immunomodulators, antibiotics, and ADA induction. Surgical interventions were determined by the surgeon's discretion in the control group and assisted by every 12th week EUS in the intervention group. Primary and secondary endpoints where complete drainage cessation at week 48 was fistula status per EUS, respectively. Twenty patients were enrolled: 11 control and 9 EUS guidance. At 24 weeks, 7/9 (78%) in EUS group and 3/11 (27%) in control group had drainage cessation (P = 0.04). This significant difference was lost at week 48 (P = 0.44). Three patients in the EUS and 1 in the control group had additional surgical intervention. Those in the EUS group had more rapid escalation of ADA dosing (P = 0.003). There was no difference in the change in PDAI at week 48 versus baseline (P = 0.81). Rectal EUS-guided ADA therapy for CD perianal fistulas showed an initial benefit at 24 weeks, which was lost at week 48. This is likely due to small sample size and higher fistula closure in the controls. However, the faster rate of fistula resolution is a clinically significant finding.

A Prospective Evaluation of the Ligation of the Intersphincteric Tract Procedure for Complex Anal Fistula in Patients With Crohn's Disease

To evaluate 2- and 12-month outcomes after ligation of the intersphincteric fistula tract (LIFT) in Crohn's disease (CD). Surgical approaches to perianal fistulas in CD are frequently ineffective and hampered by concerns over adequate wound healing and sphincter injury. The efficacy of LIFT in CD patients is unknown. Consecutive cases of CD patients with transsphincteric fistulas were prospectively analyzed. Fistula healing and 2 validated quality-of-life indices were assessed. Fifteen CD patients (9 women; mean age = 34.8 years) were identified. Location of the fistula was lateral (n = 10; 67%) or midline (n = 5; 33%). LIFT site healing was seen in 9 patients (60%) at 2-month follow-up. No patient developed fecal incontinence. LIFT site healing was seen in 8 of the 12 patients (67%) with complete 12-month follow-up. Significant factors for long-term LIFT site healing were lateral versus midline location (P = 0.02) and longer mean fistula length (P = 0.02). Patients who had successful operations significantly improved both their mean Wexner Perianal Crohn's Disease Activity Index and McMaster Perianal Crohn's Disease Activity Index quality-of-life scores at 2-month follow-up (14.0-3.8, P = 0.001, and 10.4-1.8, P = 0.0001, respectively). CD-associated anal fistulas may be treated with LIFT. This surgical procedure is a safe, outpatient procedure that minimizes both perianal wound creation and sphincter injury.