Crohn's Perianal Fistulas Research Articles

The Impact of Obesity on the Prevalence and Complications of Perianal Fistulas of Crohn's Disease.

The incidence of obesity in patients with inflammatory bowel disease (IBD) is increasing and there are limited data on the impact of obesity on perianal fistulas in Crohn's disease (CD). We aim to examine the relationship between obesity and the prevalence and complications of Crohn's perianal fistulas. We conducted a cross-sectional study of CD patients treated at a tertiary care center from 2012 to 2022. Obesity was defined as maximum BMI > 30kg/m2 and further subdivided into 5 BMI categories. The prevalence of perianal fistulas was defined by any history of perianal fistula. The complications of perianal fistulas were measured by five variables including complex fistulas, history of perianal fistula surgery, number of perianal surgeries, history of fecal diversion, and median time to first anal surgery. In all, 704 patients with CD were included; 31.1% were obese. There was no significant association between obesity and prevalence of perianal fistulas (p = 0.719), complex fistulas (p = 0.144), history of perianal surgery (p = 0.146), ≥ 1 perianal surgeries (p = 0.220), fecal diversion (p = 0.705), or median time to first perianal surgery (p = 0.192). Increasing BMI category was not associated with the prevalence of perianal fistulas (p = 0.944), complex fistulas (p = 0.089), perianal surgery (p = 0.583), ≥ 1 perianal surgeries (p = 0.114), fecal diversion (p = 0.542), or median time to first perianal surgery (p = 0.486).When comparing those with perianal fistulas to those without, there was no significant difference in rates of obesity (p = 0.876). There was no association between obesity and the prevalence and complications of Crohn's perianal fistulas.

Collagen Paste Injection in Crohn's Disease Perianal Fistula: Long-term Outcomes of a Pilot, Prospective Cohort Study.

Crohn's perianal fistula represents a challenging condition to treat. Sphincters-preserving surgical techniques are increasingly being adopted as repeated surgical procedures may lead to various degrees of incontinence. This prospective study aims to assess the long-term efficacy of collagen paste application in patients with simple and complex Crohn's perianal fistulas. Patients with Crohn's perianal fistula (simple or complex) and inactive luminal disease were enrolled. The fistula tract was treated by curettage and injection of acellular, porcine dermal collagen paste between 2019 and 2021. The primary endpoint was the clinical healing of the fistula at 12 and 24 months, defined as the absence of suppuration on clinical examination. The trial was preregistered on a public repository (ClinicalTrials.gov; NCT03776825). Fourteen patients were included in the study, ten patients (71%) had complex perianal fistula. All patients underwent previous fistula operations. Nine patients (64%) reached complete clinical remission at 12 months, two patients (14%) had a clinical recurrence six months after surgery, and three patients (21%) at 12 months follow-up. Three relapsed patients presented postoperative abscesses. Twelve patients (86%) were followed up at 24 months, no further clinical recurrences or complications were observed and the complete healing rate was 58%. No continence disturbances were recorded after collagen paste injection. The results suggest that collagen paste injection may represent a safe and effective option for Crohn's perianal fistulas, worth further investigation in larger trials.

Real-life effectiveness of allogeneic expanded adipose-derived mesenchymal stem cell therapy for perianal fistulizing refractory Crohn's disease

BackgroundReal life data about the long-term efficacy of darvadstrocel for treating perianal fistulas in Crohn's disease (CD) remain scarce. Aim: To report the effectiveness and safety of darvadstrocel therapy to close perianal fistula in a real-life cohort of CD patients. MethodsAll patients with CD suffering complex draining perianal fistulas who consecutively underwent administration of a single local injection of darvadstrocel at two centres were followed up and evaluated. The primary endpoint was clinical remission (closure of all external openings with no discharge at pressure) at week 24. Combined remission (defined as clinically plus MRI-assessed fistula closure) were also assessed at week 24 and 52. ResultsA total of 36 CD patients (19 Male, mean age 38.5 years) were included with a median follow up of 16 months. Clinical remission was achieved in 17 out of 36 patients (47.2 %) and combined remission in 15 out of 36 patients (41.6 %) at week 24. At week 52, clinical and combined remission was achieved in 17 out of 36 patients (47.2 %) and in 15 out of 33 evaluable patients (45.4 %), respectively. ConclusionIn this real-world setting, a successful response to darvadstrocel therapy based on clinical remission was reported in around half of the patients and combined remission including radiological assessment in more than 4 out of 10 patients.

Mesenchymal stem cells for perianal fistulizing Crohn’s disease (systematic review and meta-analysis)

AIM: to compare the efficacy (fistulas healing rate) and safety (morbidity rate) of mesenchymal stem cells (MSC) and placebo in patients with perianal fistulizing Crohn’s disease (PFCD). PATIENTS AND METHODS: a systematic review and meta-analysis of clinical trials, comparing the results of treatment of PFCD with single local administration of MSCs or placebo was performed. The meta-analysis included 5 randomized clinical trials and the results of treatment of 289 patients were analyzed. RESULTS: the meta-analysis demonstrates the high efficacy of a single local administration of MSCs for PFCD compared with placebo (OR = 2.10, CI 1.28–3.46, p = 0.003). The most common postoperative complications — abscesses and fistulas — are probably associated with the natural course of the disease and do not differ significantly between the groups. The results of surgery may be affected by the type, source and concentration of MSCs, the method of delivery and the number of injections. CONCLUSION: local administration of mesenchymal stem cells is an effective and safe method for perianal fistulas in Crohn’s disease, however, the presence of significant limitations in the meta-analysis makes it cautious about the results obtained and requires further randomized trials.

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

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

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.

Use of Darvadstrocel (Allogenic Stem Cell Therapy) for Crohn's Fistulas in Real Clinical Practice: The National Project to Implement Mesenchymal Stem Cell for the Treatment of Perianal Crohn's Fistula (the PRIME Study).

Perianal fistulas may affect 15% to 50% of patients with Crohn's disease. Treatment is complex, requiring a multidisciplinary approach. Darvadstrocel (allogenic mesenchymal cells obtained from lipoaspirates) was approved in 2018 by the European and Spanish Agencies of Medicines and Medical Products as a treatment for fistulas in Crohn's disease. Recent guidelines from the European Crohn's and Colitis Organisation and Spanish Working Group on Crohn's Disease and Ulcerative Colitis state that darvadstrocel is effective with a favorable safety profile and a strong level of evidence (n = 2). Presenting real-world effectiveness data for darvadstrocel in a Spanish population. Observational retrospective cohort study with prospective data gathering. The study was conducted at 14 institutions in Spain. From November 2019 to April 2022, all patients (n = 73) treated with darvadstrocel in these institutions were included, fulfilling the following criteria: 1) complex fistula/s in a patient with Crohn's disease; 2) failure of conventional and antitumor necrosis factor treatment; and 3) the absence of collections of >2 cm confirmed by pelvic MRI at the time of surgery. Darvadstrocel treatment. Clinical response (closure of 50% or more of external openings), complete clinical closure (100% of external openings), and radiological closure (no fluid collection >2 cm, edema, or inflammation) evaluated 6 months after treatment. Clinical response was observed in 63 patients (86.3%), complete clinical closure in 50 patients (68.5%), and radiological closure in 45 patients (69.2%). Combined clinical and radiological response was observed in 41 patients (63.1%). Not all clinically healed patients had radiological closure, and vice versa. No serious adverse events were reported. Retrospective nature of the study. Study results were consistent with those reported in previous clinical trials, real-world efficacy findings from the INSPIRE study (assessing darvadstrocel effectiveness in Europe, Israel, Switzerland, United Kingdom, and Japan), and previously published literature. Darvadstrocel was effective and demonstrated a favorable safety profile when used in normal clinical practice for the treatment of fistulas in Crohn's disease. See Video Abstract . ANTECEDENTES:Las fístulas perianales pueden afectar entre el 15 y el 50% de los pacientes con enfermedad de Crohn. El tratamiento es complejo y requiere un enfoque multidisciplinario. El darvadstrocel (células mesenquimales alogénicas obtenidas a partir de lipoaspirados) fue aprobado en 2018 por las Agencias Europea y Española de Medicamentos y Productos Sanitarios como tratamiento de las fístulas en la EC. Las recientes directrices de la Organización Europea de Crohn y Colitis y del Grupo de Trabajo Español sobre la Enfermedad de Crohn y Colitis Ulcerosa afirman que darvadstrocel es eficaz con un perfil de seguridad favorable y un sólido nivel de evidencia (2).OBJETIVO:Presentar datos de eficacia real de darvadstrocel en población española.DISEÑO:Estudio de cohorte retrospectivo observacional con recopilación prospectiva de datos.ESCENARIO:14 instituciones.PACIENTES:Desde noviembre de 2019 hasta abril de 2022, se incluyeron todos los pacientes (73) tratados con darvadstrocel en estas instituciones, que cumplieron los siguientes criterios: 1) fístula/s compleja/s en un paciente con enfermedad de Crohn; 2) fracaso del tratamiento convencional y anti factor de necrosis tumoral; 3) ausencia de colecciones > 2 cm confirmada por resonancia magnética pélvica en el momento de la cirugía.INTERVENCIONES:Tratamiento con Darvadstrocel.PRINCIPALES MEDIDAS DE RESULTADO:Respuesta clínica (cierre de ≥50% de las aberturas externas), cierre clínico completo (100% de las aberturas externas) y cierre radiológico (sin acumulación de líquido >2 cm, sin edema ni inflamación) evaluados 6 meses después del tratamiento.RESULTADOS:Se observó respuesta clínica en 63 pacientes (86.3%), cierre clínico completo en 50 pacientes (68.5%) y cierre radiológico en 45 pacientes (69.2%). Se observó respuesta clínica y radiológica combinada en 41 pacientes (63.1%). No todos los pacientes clínicamente curados tuvieron cierre radiológico y viceversa. No hubo eventos adversos graves reportados.LIMITACIONES:Estudio retrospectivoCONCLUSIONES:Los resultados del estudio fueron consistentes con los informados en ensayos clínicos anteriores, los hallazgos de eficacia en el mundo real del estudio INSPIRE (que evalúa la efectividad de darvadstrocel en Europa, Israel, Suiza, el Reino Unido y Japón) y la literatura publicada anteriormente. Darvadstrocel fue eficaz y demostró un perfil de seguridad favorable cuando se utiliza en la práctica clínica habitual para el tratamiento de fístulas en la enfermedad de Crohn. (Traducción-Dr. Jorge Silva Velazco ).

Traitement des fistules anales réfractaires à l’Infliximab au cours de la maladie de Crohn : Mise au point

Treatment of complex perianal fistulas in Crohn's disease remains a challenge especially after the failure of Infliximab. Update on the different therapeutic alternatives for anal fistula in Crohn's disease after failure of Infliximab. A research in the medical literature on PubMed and Google Scholar was carried out. We included cohort studies, reviews and randomized double-blinded therapeutic trials. Case reports and fundamental research studies have been excluded. Anti-TNF therapy, notably Infliximab remain the therapeutic option of choice. Since Infliximab efficacy has been estimated at 60%, with a significant loss-of response rate, new therapeutic strategies have been evaluated and may offer new opportunities for the management of anal fistulas: for example, Ustekinumab could be effective after failure of anti-TNF therapy, although further studies are required. Recent guidelines suggest that injection of mesenchymal stem cells is an effective and safe treatment for complex fistulas. Other surgical options have been proposed, such as endorectal advancement flap, fibrin glue injection, anal fistula plug and ligation of the intersphincteric fistula tract, but all with limited and debatable efficacy. Given the failure rate of all these options, new strategies are currently being evaluated. Anal fistulas in Crohn's disease are a real therapeutic challenge. New medical and surgical therapies are currently being evaluated, with promising results.

Long-term outcome of stem cell transplantation with and without anti-tumor necrotic factor therapy in perianal fistula with Crohn's disease.

Stem cell transplantation is a promising therapeutic option for curing perianal fistula in Crohn's disease (CD). Anti-tumor necrotic factor (TNF) therapy combined with drainage procedure is effective as well. However, previous studies are limited to proving whether the combination treatment of biologics and stem cell transplantation improves the effect of fistula closure. This study aimed to evaluate the long-term outcomes of stem cell transplantation and compare Crohn's perianal fistula (CPF) closure rates after stem cell transplantation with and without anti-TNF therapy, and to identify the factors affecting CPF closure and recurrence. The patients with CD who underwent stem cell transplantation for treating perianal fistula in our institution between Jun 2014 and December 2022 were enrolled. Clinical data were compared according to anti-TNF therapy and CPF closure. A total of 65 patients were included. The median age of females was 26 years (range: 21-31) and that of males was 29 (44.6%). The mean follow-up duration was 65.88 ± 32.65 months, and complete closure was observed in 50 (76.9%) patients. The closure rates were similar after stem cell transplantation with and without anti-TNF therapy (66.7% vs 81.6% at 3 year, P = 0.098). The patients with fistula closure had short fistulous tract and infrequent proctitis and anorectal stricture (P = 0.027, 0.002, and 0.008, respectively). Clinical factors such as complexity, number of fistulas, presence of concurrent abscess, and medication were not significant for closure. The cumulative 1-, 2-, and 3-year closure rates were 66.2%, 73.8%, and 75.4%, respectively. Anti-TNF therapy does not increase CPF closure rates in patients with stem cell transplantation. However, both refractory and non-refractory CPF have similar closure rates after additional anti-TNF therapy. Fistulous tract length, proctitis, and anal stricture are risk factors for non-closure in patients with CPF after stem cell transplantation.

Patient and Caregiver Perspectives on Their Experiences With Crohn's Perianal Fistulas.

Little is known about patients' perception of care and management of Crohn's perianal fistulas (CPF). This study was conducted to understand US patient and caregiver attitudes and challenges to CPF care. Patients with CPF and caregivers of patients with CPF completed a 36-question survey about their perceptions and challenges regarding the diagnosis, treatment, and overall management of CPF. Patients/caregivers were recruited via online Crohn's and fistula support group websites and forums and via their gastroenterologists (GEs) and surgeons from October 2020 through January 2021. The survey was completed by 96 patients and 54 caregivers. Respondents reported over 60% and 14%-23% of CPF were diagnosed and treated by a GE or surgeon, respectively. Nearly all patients/caregivers wanted to be involved in treatment decision-making with their physicians (81%). While the majority of patients/caregivers were satisfied with their quality of care (65%) and access to care (67%), racial disparities exist and there is room for improvement. A smaller proportion of non-White versus White patients/caregivers reported satisfaction with care quality (39% vs 72%, respectively) and access to care (57% vs 69%, respectively). Half of non-White patient/caregivers (50%) versus 69% of White patient/caregivers knew where to access CPF information. Most patients/caregivers (69%) stated that they would benefit from more information on managing day-to-day CPF symptoms. Significant barriers perceived by patients/caregivers to receiving optimal CPF care included lack of effective treatments (69%) and lack of access to specialist care (68%). Improvements in multidisciplinary CPF care are required to optimize treatment.

Mesenchymal stem cell therapy for Crohn's perianal fistula-a real-world experience.

Remission rates of medically and surgically treated complex perianal fistulas in Crohn's disease are low. Recently, trials have demonstrated the potential for long-term remission with local injection of allogeneic adipose-derived mesenchymal stem cells (darvadstrocel). Our aim was to analyse outcomes from our real-world experience with this new treatment. All patients with Crohn's disease suffering complex perianal fistulas who consecutively underwent administration of darvadstrocel at two centres were followed up and evaluated. Patients were assessed for clinical remission, response, failure, and any complications during follow-up. The results of all patients with a minimum of 3 months' follow-up are presented. Thirty-three patients with Crohn's disease and complex perianal fistulas were included. Of these, 20 (61%) experienced clinical remission that was maintained for a mean follow-up of 14 (3-32) months. A total of 24 of 33 (73%) experienced at least 3 months of clinical remission, with four later having recurrence (3-12 months). Among the remaining nine patients who did not experience clinical remission, two (6%) had partial remission (such as one of two fistulas closing), two (6%) showed signs of response but not remission, and five (15%) showed no signs of healing. The mean time to maintained clinical remission was 6 weeks (range 2 weeks to 6 months), and there were no severe adverse events. In this real-world experience, treatment of Crohn's disease complex perianal fistulas with darvadstrocel had a 61% success rate for maintained clinical remission.

Local fistula injection of allogeneic human amnion epithelial cells is safe and well tolerated in patients with refractory complex perianal Crohn's disease: a phase I open label study with long-term follow up

Local fistula injection of mesenchymal stromal/stem cells (MSC) is effective for complex perianal Crohn's fistulas but is also expensive and requires specialised facilities for cell revival before administration. Human amnion epithelial cells (hAEC) are non-MSC cells with therapeutic properties. The primary aim of this study was safety of hAEC therapy. Secondary aims included hAEC efficacy, feasibility of the protocol and impact on quality of life. A phase I open label study of ten adults with active complex Crohn's perianal fistulas refractory to conventional treatment, including anti-tumour necrosis factor alpha therapy, was undertaken. A single dose of hAEC was injected into the fistula tract(s) after surgical closure of the internal opening(s). Study outcomes were assessed at week 24 with follow up for at least 52 weeks. Local injection of hAEC was safe, well tolerated and the injection procedure was feasible. Complete response occurred in 4 patients, and a partial response in an additional 4 patients. There was a mean reduction in the Perianal Disease Activity Index of 6.5 points (95% CI-9.0 to-4.0, p=0.0002, paired t-test), modified Van Assche MRI Index of 2.3 points (95% CI-3.9 to-0.6, p=0.012, paired t-test) and a mean improvement of 15.8 points (95% CI 4.9 to 26.8, p=0.010, paired t-test) in quality of life using the Short IBD-Questionnaire in complete responders. Local injection of hAEC therapy for refractory complex perianal fistulising Crohn's disease appears safe, well-tolerated, feasible and demonstrated improvement. Quality of life is improved in those who achieve complete fistula healing. This study was funded by competitive research grant funding from the Gastroenterological Society of Australia Seed Grant2018.

Multi-national observational study to assess quality of life and treatment preferences in patients with Crohn's perianal fistulas.

Patients with Crohn's disease (CD) are at risk of developing complications such as perianal fistulas. Patients with Crohn's perianal fistulas (CPF) are affected by fecal incontinence (FI), bleeding, pain, swelling, and purulent perianal discharge, and generally face a higher treatment burden than patients with CD without CPF. To gain insights into the burden of illness/quality of life in patients with CPF and their treatment preferences and satisfaction. This cross-sectional observational study was conducted in patients with CD aged 21-90 years via a web-enabled questionnaire in seven countries (April-August 2021). Patients were recruited into three cohorts: Cohort 1 included patients without perianal fistulas; cohort 2 included patients with perianal fistulas without fistula-related surgery; and cohort 3 included patients with perianal fistulas and fistula-related surgery. Validated patient-reported outcome measures were used to assess quality of life. Drivers of treatment preferences were measured using a discrete choice experiment (DCE). In total, 929 patients were recruited (cohort 1, n = 620; cohort 2, n = 174; cohort 3, n = 135). Short Inflammatory Bowel Disease Questionnaire scores were worse for patients with CPF (cohorts 2 and 3) than for those with CD without CPF (cohort 1): Mean score 3.8 and 3.7 vs 4.1, respectively, (P < 0.001). Similarly, mean Revised FI and FI Quality of Life scores were worse for patients with CPF than for those with CD without CPF. Quality of Life with Anal Fistula scores were similar in patients with CPF with or without CPF-related surgery (cohorts 2 and 3): Mean score 41 and 42, respectively. In the DCE, postoperative discomfort and fistula healing rate were the most important treatment attributes influencing treatment choice: Mean relative importance 35.7 and 24.7, respectively. The burden of illness in CD is significantly higher for patients with CPF and patients rate lower postoperative discomfort and higher healing rates as the most desirable treatment attributes.

Allogenic stem cells for Crohn's anal fistulas: Treating early improves the deep remission rate.

The aim of this study was to evaluate the real-life clinical and radiological efficacy of darvadstrocel injection into complex perianal fistulas in Crohn's disease. Secondary endpoints were to assess symptomatic efficacy, adverse effects and factors associated with complete combined clinical-radiological response (deep remission). After marketing the product in France, all first patients treated consecutively were included. A complete clinical response was defined by a complete closure of all external openings with no discharge on pressure. A complete radiological response (MRI), evaluated at least after six months of follow-up, was defined by a completely fibrotic sequela without abscess. A deep remission was defined as the association of a complete clinical response with a complete radiological response. A total of 43 patients were included (M/F: 22/21, median age 37 [26-45] years). The fistulas were already drained with seton(s) and were on biologic treatment. After a median follow-up of 383 (359-505) days, 28 (65%) patients showed a clinical response (22 complete and 6 partial) and 16 (37%) achieved a deep remission. The Perineal Disease Activity Index decreased significantly after treatment: 39 (91%) patients reported symptomatic improvement in terms of discharge, pain, and induration, and 28 (65%) no longer had any perineal symptoms. No severe adverse events were reported. A short history of Crohn's disease <3 years was significantly associated with deep remission (OD 4.5 [1.0-19.1], p = 0.04). Darvadstrocel injection resulted in a clinical response for two thirds of patients and deep remission for one third. A shorter duration of Crohn's disease was associated with deep remission.

Patients' Perspectives, Experiences, and Concerns With Perianal Fistulae: Insights From Online Targeted-Disease Forums.

Perianal fistulae can undermine physical, emotional, and social well-being in patients with Crohn's disease and are challenging to manage. Social media offers a rich opportunity to gain an in-depth understanding of the impact of perianal fistulae on patients' daily lives outside of controlled environments. In this study, we conducted social media analytics to examine patients' experiences with perianal fistulae and assessed the impact of perianal fistulae on patients' behavior and overall well-being. We used a mixed-method approach to examine 119 986 publicly available posts collected from 10 Crohn's disease forums in the United States between January 01, 2010 and January 01, 2020. Discussions related to Crohn's perianal fistulae were retrieved. We randomly selected 700 posts and qualitatively analyzed them using an inductive thematic approach. We then applied a latent Dirichlet allocation probabilistic topic model to explore themes in an unsupervised manner on the collection of 119 986 posts. In the qualitative analysis, 5 major themes were identified: (1) burden of perianal fistula; (2) challenges associated with treatment; (3) online information seeking and sharing; (4) patient experiences with treatments; and (5) patients' apprehension about treatments. In the quantitative analysis, the percentages of posts related to the major themes were (1) 20%, (2) 29%, (3) 66%, and (4) 28%, while the topic model did not identify theme 5. Social media reveals a dynamic range of themes governing patients' perspectives and experiences with Crohn's perianal fistulae. In addition to the biopsychosocial burden, patients frequently express dissatisfaction with current treatments and often struggle to navigate among available management options.

Preferred definitive surgical management of Crohn's perianal fistulas and factors influencing surgical decision making in Australia and New Zealand.

Preferred definitive surgical management of Crohn's perianal fistulas and factors influencing surgical decision making in Australia and New Zealand.

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.

Short-term anti-TNF therapy with surgical closure versus anti-TNF therapy alone for Crohn's perianal fistulas (PISA-II): long-term outcomes of an international, multicentre patient preference, randomised controlled trial

Short-term anti-TNF therapy with surgical closure versus anti-TNF therapy alone for Crohn's perianal fistulas (PISA-II): long-term outcomes of an international, multicentre patient preference, randomised controlled trial

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

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

Three-dimensional modelling as a novel interactive tool for preoperative planning for complex perianal fistulas in Crohn's disease.

The aim of this study is to demonstrate the added value of three-dimensional (3D) reconstruction models and artificial intelligence for preoperative planning in complex perianal Crohn's disease. MRI is the gold standard for diagnosis of complex perianal fistulas and abscess due to its high sensitivity, but it lacks high specificity values. This creates the need for better diagnostic models such as 3D image processing and reconstruction (3D-IPR) with artificial intelligence (AI) algorithms. This is a prospective study evaluating the utility of 3D reconstruction models from MRI in four patients with perineal Crohn's disease (pCD). Four pCD patients had 3D reconstruction models made from pelvic MRI. This provided a more visual representation of perianal disease and made possible location of the internal fistula orifice, seton placement in fistula tracts and abscess drainage. Three-dimensional reconstruction in CD-associated complex perianal fistulas can facilitate disease interpretation, anatomy and surgical strategy, potentially improving preoperative planning as well as intraoperative assistance. This could probably result in better surgical outcomes to control perianal sepsis and reduce the number of surgical procedures required in these patients.