Search

Background: Perianal fistulas are a debilitating complication of Crohn's disease (CD). Due to unknown reasons, CD-associated fistulas are in general more difficult to treat than cryptoglandular fistulas (non-CD-associated). Understanding the immune cell landscape is a first step towards the development of more effective therapies for CD-associated fistulas. In this work, we characterized the composition and spatial localization of disease-associated immune cells in both types of perianal fistulas by high-dimensional analyses., Methods: We applied single-cell mass cytometry (scMC), spectral flow cytometry (SFC), and imaging mass cytometry (IMC) to profile the immune compartment in CD-associated perianal fistulas and cryptoglandular fistulas. An exploratory cohort (CD fistula, n = 10; non-CD fistula, n = 5) was analyzed by scMC to unravel disease-associated immune cell types. SFC was performed on a second fistula cohort (CD, n = 10; non-CD, n = 11) to comprehensively phenotype disease-associated T helper (Th) cells. IMC was used on a third cohort (CD, n = 5) to investigate the spatial distribution/interaction of relevant immune cell subsets., Results: Our analyses revealed that activated HLA-DR+CD38+ effector CD4+ T cells with a Th1/17 phenotype were significantly enriched in CD-associated compared with cryptoglandular fistulas. These cells, displaying features of proliferation, regulation, and differentiation, were also present in blood, and colocalized with other CD4+ T cells, CCR6+ B cells, and macrophages in the fistula tracts., Conclusions: Overall, proliferating activated HLA-DR+CD38+ effector Th1/17 cells distinguish CD-associated from cryptoglandular perianal fistulas and are a promising biomarker in blood to discriminate between these 2 fistula types. Targeting HLA-DR and CD38-expressing CD4+ T cells may offer a potential new therapeutic strategy for CD-related fistulas., (© 2024 Crohn’s & Colitis Foundation. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation.)

Background: Real 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., Methods: All 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., Results: A 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., Conclusion: In 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., Competing Interests: Declaration of competing interest R Altwegg, Maria Alonso-Gomez, declares no conflict of interest related to this work. S Nancey declares counseling, boards, transports or fees from Abbvie, Biogen, HAC-pharma, Janssen, MSD, Novartis, Pfizer, Takeda, Tillots, BMS, Amgen, and Fresenius. E Cotte declares fees from Abbvie, Takeda G Boschetti declares fees from Abbvie, Takeda, Janssen Anne Laure Charlois: None Claire Gay: Takeda, Abbvie, Janssen. Pauline Danion: none Emilie Malezieux: Nonea, (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Background: The efficacy of ustekinumab and vedolizumab for treating complex perianal fistula in Crohn's disease has been barely studied. We aimed to assess treatment persistence, clinical remission, and safety of these drugs in this context., Methods: Crohn's disease patients who had received ustekinumab or vedolizumab for the indication of active complex perianal fistula, were included. Clinical remission was defined according to Fistula Drainage Assessment Index (no drainage through the fistula upon gentle pressure) based on physicians' assessment., Results: Of 155 patients, 136 received ustekinumab, and 35 vedolizumab (16 received both). Median follow-up for ustekinumab was 27 months. Among those on ustekinumab, 54 % achieved remission, and within this group, 27 % relapsed during follow-up. The incidence rate of relapse was 11 % per patient-year. Multivariate analysis found no variables associated with treatment discontinuation or relapse. Median follow-up time for patients receiving vedolizumab was 19 months. Remission was achieved in 46 % of the patients receiving vedolizumab, and among them, 20 % relapsed during follow-up. The incidence rate of relapse was 7 % per patient-year. Adverse events were mild in 6 % on ustekinumab and 8 % on vedolizumab., Conclusion: Ustekinumab and vedolizumab appear effective, achieving remission in around half of complex perianal fistula patients, with favorable safety profiles., Competing Interests: Declaration of funding interests None, (Copyright © 2024 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Perianal fistulizing Crohn's disease (CD) is a severe gastrointestinal disorder causing extensive mucosal damage with limited treatment options. Severe manifestations of the disease appear at higher rates in non-Europeans but the genetic and cellular mechanisms driving the disease phenotypes remain poorly understood. Herein, we tested whether pathologic determinants in the epithelial stem cell compartment could be detected at the transcript level in rectal organoids derived from a diverse patient population. Rectal organoid and mucosal cells from endoscopic biopsies of each patient having perianal fistulizing CD or no disease controls were prepared for and sequenced at the single cell level. After cell type annotations based on expressed marker genes, samples were analyzed by principal components, for differential transcript expression, cell type proportions, and pathway enrichment. After QC, we produced 77,044 rectal organoid cells (n = 13 patients; 8 CD, 5 controls) with high quality sequences that identified 10 distinct epithelial subtypes, that we compared to 141,367 mucosal epithelial cells (n = 29 patients; 18 CD, 11 controls). Consistent with mucosal epithelial cells, rectal organoids prominently displayed disease signatures represented by the stem and transit amplifying regions of the rectal crypt, including alterations in transcriptional signatures of metabolic, epigenetic, and proliferating pathways. Organoids also retained their gender- and ancestral-specific gene expression signatures. However, they lacked many of the inflammatory signatures observed in epithelial cells from diseased mucosa. Perianal CD patient derived rectal organoids reflect gene expression signatures related to disease, gender, and ancestry, suggesting they harbor inherent properties amenable to further patient-specific, disease-related experimentation., (© 2024. The Author(s).)

Background: Postoperative urinary retention (POUR) is a common complication characterized by fullness of the bladder without the ability to urinate. Its etiology in proctology surgery is multifactorial. This study aimed to identify the risk factors for POUR after radical surgery for anal fistula., Methods: We retrospectively reviewed the clinical records of 511 patients who underwent radical surgery for anal fistula at the China-Japan Friendship Hospital from August 2022 to December 2023. Risk factors for POUR were analyzed by means of binary logistic regression analyses., Results: POUR occurred in 57 patients (11.2%) within 48 h post-surgery, and males were predominantly affected (84.4%). Independent risk factors included a history of urological disease (OR = 6.048; p < 0.001), incisions at position 1 (OR = 2.228; p = 0.046), high anal fistula (OR = 4.768; p < 0.001), VAS score ≥ 7 (OR = 2.805; p = 0.010), and GAD-7 score ≥ 5 (OR = 2.405; P = 0.024)., Conclusion: POUR is a significant complication post-radical surgery for anal fistula, particularly among patients with urological disease, high anal fistula, and incisions at position 1. Surgeons should pay more attention to surgical methods for high anal fistulas and fistulas in the anterior rectum, and monitor postoperative bladder volume in high-risk patients. Enhanced postoperative pain and anxiety management can reduce the incidence of POUR and prevent long-term bladder damage., (© 2024. The Author(s).)

Introduction: Fistula is a common complication of Crohn's disease (CD). Treatment with biologics has been associated with fistula healing. Long-term persistence is an important factor for a chronic inflammatory process such as fistula. This study described 24-month persistence and time-to-surgery endpoints among bio-naïve patients with CD and intestinal fistula who were initiated on ustekinumab., Methods: Adults with CD and any enteric or perianal fistula initiated on ustekinumab (index date) between September 23, 2016, and March 2, 2022, were selected from the IQVIA PharMetrics ® Plus database and followed up to 24 months. Persistence on ustekinumab (no gaps in days of supply of > 120 days) and composite endpoints of being persistent while on monotherapy and persistent while corticosteroid free were also assessed. The date of surgery was defined as the date of first claim for any CD-related surgeries. Persistence and time-to-surgery endpoints were assessed from the index date until the earliest of discontinuation (event), immunomodulator or other biologic use (event), corticosteroid use (event), date of surgery (event), 24-month follow-up or data end (censoring) using Kaplan-Meier analyses., Results: The sample included 445 patients (mean age: 42.8 years; 56.6% female). The most common type of fistula was anal fistula (36.0%). At 24 months after ustekinumab initiation, 64.2% of patients remained persistent (95% confidence interval [CI] 55.8-71.4). Furthermore, 53.3% of patients were persistent while on monotherapy (95% CI 45.1-60.7), and 45.6% of patients were persistent while being corticosteroid free (95% CI 36.9-53.8). At 24 months, 22.8% (95% CI 17.0-30.3) of patients underwent any CD-related surgery., Conclusion: This study quantified long-term persistence on ustekinumab among bio-naïve patients with CD and fistula. Over half of patients initiated on ustekinumab were persistent and persistent while on monotherapy 24 months after initiation. Time-to-surgery estimate was comparable to existing evidence. These findings support ustekinumab as a treatment option for long-term management of CD with fistula., (© 2024. The Author(s), under exclusive licence to Springer Healthcare Ltd., part of Springer Nature.)

Perianal fistulas can develop in around 30% of patients with Crohn's disease (CD) and are associated with impaired quality of life and worse outcomes including increased rates of hospitalizations and surgeries. 1 The cornerstone of pharmacologic treatment for perianal fistulizing CD is anti-tumor necrosis factor therapy, mainly infliximab and adalimumab (ADM). 2 Therapeutic drug monitoring (TDM) can be used to identify potential pharmacokinetic and pharmacodynamic issues and avoid or manage unwanted outcomes, such as primary nonresponse and secondary loss of response. 3 There are several exposure-response relationship data demonstrating a positive correlation between serum infliximab concentrations and favorable objective therapeutic outcomes in patients with perianal fistulizing CD. 4 Nevertheless, there are only limited data, which is mostly from small retrospective studies regarding the association of ADM concentration and outcomes in patients with perianal fistulizing CD. 4-8 Furthermore, the optimal ADM concentration for fistula healing still remains to be elucidated. This is clinically important because drug concentration cutoffs are used in reactive and proactive TDM algorithms to define therapeutic drug concentrations. This study investigates the association of maintenance ADM concentrations with complete fistula healing (CFH) and identifies an optimal ADM concentration threshold for CFH., (Copyright © 2024 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Perianal fistulizing Crohn's disease (CD) represents a severe phenotype of CD that is associated with significant morbidity and reduction in quality of life. Perianal fistulizing CD is caused by a complex interplay of genetic predisposition, immune dysregulation, gut dysbiosis, and various unknown physiological and mechanical factors. A multidisciplinary approach is hence required for optimal management . A detailed anatomical description and classification of perianal fistula, including comprehensive clinical, endoscopic, and radiological diagnostic workup, is an important prerequisite to treatment. For simple perianal fistulas, use of antibiotics and immunomodulators, with or without fistulotomy, are appropriate measures. The medical management of complex perianal fistula, on the other hand, requires adequate control of infection before initiation of therapy with immunomodulators. In active complex perianal fistula, anti-tumor necrosis factors remain the most accepted therapy, with concomitant use of antibiotics or immunomodulators enhancing the efficacy. For patients refractory to anti-tumor necrosis factors, treatment with anti-integrins, anti-interleukins, and small molecules is being evaluated. Mesenchymal stem cells, hyperbaric oxygen therapy, and exclusive enteral nutrition have also been investigated as adjunct therapies. Despite the expansion of the medical armamentarium, a large proportion of the patients require surgical interventions. In this review, we provide an up-to-date overview of the pathophysiology, clinical presentation, diagnosis, and medical management of perianal fistulizing CD. A brief overview of the surgical management of perianal fistulizing CD is also provided., (© The Author(s) 2023. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background and Aims: Perianal fistuliing Crohn's disease [PFCD] is an aggressive phenotype of Crohn's disease defined by frequent relapses and disabling symptoms. A novel consensus classification system was recently outlined by the TOpCLASS consortium, which seeks to unify disease severity with patient-centred goals but has not yet been validated. We aimed to apply this to a real-world cohort and to identify factors that predict transition between classes over time., Methods: We identified all patients with PFCD and at least one baseline and one follow-up pelvic MRI [pMRI]. TOpCLASS classification, disease characteristics, and imaging indices were collected retrospectively at time periods corresponding with respective MRIs., Results: We identified 100 patients with PFCD, of whom 96 were assigned TOpCLASS Classes 1-2c at baseline. Most patients [78.1%] started in Class 2b, but changes in classification were observed in 52.1% of all patients. Male sex [72.0%, 46.6%, 40.0%, p = 0.03] and prior perianal surgery [52.0% vs 44.6% vs 40.0%, p = 0.02] were more frequently observed in those with improved class compared to unchanged and worsened class. Baseline pMRI indices were not associated with changes in classification; however, greater improvements in mVAI, MODIFI-CD, and PEMPAC were seen among those who improved. Linear mixed effect modelling identified only male sex [-0.31, 95% CI -0.60 to -0.02] with improvement in class., Conclusion: The TOpCLASS classification highlights the dynamic nature of PFCD over time. However, our ability to predict transitions between classes remains limited and requires prospective assessment. Improvement in MRI index scores over time was associated with a transition to lower TOpCLASS classification., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: The efficacy of injections of mesenchymal stem cells (MSC) for anal fistula treatment may be impaired by the persistence of stools passing into the fistula, causing bacterial contamination and a local inflammatory reaction. We aimed to compare remission rates between patients treated by MSC injection with simple sutures and those treated with a rectal advancement flap., Methods: This single-center prospective study compared the first patients who underwent internal opening closure with sutures with the subsequent patients treated with a flap. Complete clinical remission was defined as complete closure of the external opening(s) without pain or discharge, and complete radiological remission was defined as a Magnifi-CD score of 0., Results: We compared the first 42 patients who had sutures with the 20 subsequent patients who had an advancement flap. The median follow-up was 15.5 [8.8-24.9] months. The cumulative incidence of complete clinical response at M12 was 53.8% [38.1-69.6%] in the suture group versus 93.3% [77.4-100.0] in the flap group (p < 0.001). The Magnifi-CD score was 0 for 41.7% [25.5-59.2%]) of patients treated with sutures versus 72.7% [39.0-63.9%]) of patients treated with a flap (p = 0.093). Anal incontinence score did not differ between the two groups. Practicing an advancement flap was the only significant factor associated with complete clinical remission over time (adjusted HR [95% CI] of 2.6 [1.4-4.9], p = 0.003)., Conclusions: Complete clinical remission rates following MSC injection are significantly higher after closure of the internal opening with a rectal flap than after closure with sutures, without consequences on anal continence., (© 2024. Springer Nature Switzerland AG.)

Objective: To present our experience with a novel technique that combines the York-Mason transsphincteric approach with dartos muscle flap interposition to treat rectourethral fistulas., Methods: We extracted records from our prospectively kept database of 35 procedures conducted for treating rectourethral fistulas during 2002-2023; the York-Mason approach was combined with dartos muscle flap interposition in 5 cases, performed for treating rectourethral fistulas due to radical prostatectomy, all of which were referral cases., Results: All 5 patients were successfully treated and followed up for a median of 70.0 months without recurrence. Before the fistula repair, all had a diverting stoma. In all cases, the first voiding cystourethrogram revealed a healed fistula. The posterior and the scrotal incisions healed uneventfully. All patients reported normal voiding and no urinary incontinence. To date, the stoma has closed in 3 patients, all of whom had intact fecal continence and no postoperative anal stenosis., Conclusion: The transsphincteric modified York-Mason approach combined with dartos muscle flap interposition resulted in complete healing of rectourethral fistulas., Competing Interests: Declaration of Competing Interest The author has no conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Competing Interests: Declaration of Competing Interest The author declares no conflict of interest.

Competing Interests: The authors declare that they have no conflict of interest.

Background: The optimal treatment of perianal fistulizing Crohn's disease [PFCD] is unknown. We performed a systematic review with meta-analysis to compare combined surgical intervention and anti-tumour necrosis factor [anti-TNF] therapy [combined therapy] vs either therapy alone., Methods: MEDLINE, EMBASE, and Cochrane databases were searched systematically up to end December 2023. Surgical intervention was defined as an exam under anaesthesia ± setons. We calculated weighted risk ratios [RRs] with 95% confidence intervals [CIs] for our co-primary outcomes: fistula response and healing, defined clinically as a reduction in fistula drainage or number of draining fistulas and fistula closure respectively., Results: Thirteen studies were analysed: 515 patients treated with combined therapy, 330 patients with surgical intervention, and 406 patients with anti-TNF therapy with follow-up between 10 weeks and 3 years. Fistula response [RR 1.10; 95% CI 0.93-1.30, p = 0.28] and healing [RR 1.06; 95% CI 0.86-1.31, p = 0.58] was not significantly different when comparing combined therapy with anti-TNF therapy alone. In contrast, combined therapy was associated with significantly higher rates of fistula response [RR 1.25; 95% CI 1.10-1.41, p < 0.001] and healing [RR 1.17; 95% CI 1.00-1.36, p = 0.05] compared with surgical intervention alone. Our results remained stable when limiting to studies that assessed outcomes within 1 year and studies where <10% of patients underwent fistula closure procedures., Conclusion: Combined surgery and anti-TNF therapy was not associated with improved PFCD outcomes compared with anti-TNF therapy alone. Due to an inability to control for confounding and small study sizes, future, controlled trials are warranted to confirm these findings., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation.)

Objectives: 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., Methods: 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., Results: 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)., Conclusion: Most CD cases have less granulomas (≤3) and no foreign body giant cells. Ribbon-like granulomas can be seen only in CD cases., (© 2024 The Author(s). Journal of Digestive Diseases published by Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.)

Background: Perianal abscess is a common condition among adults. The treatment of choice includes early and efficient drainage. The data regarding risk factors for abscess recurrence, fistula formation, and complications are limited as recent publications mainly focus on patients with inflammatory bowel disease., Objectives: To determine risk factors for abscess recurrence and fistula formation with regard to patient and surgical characteristics., Methods: A retrospective analysis was performed on patients who presented to the emergency department and were diagnosed with perianal abscess between 2011-2020., Results: We included 983 consecutive patients; 741 men, average age 43 years. Recurrence was documented in 434 cases. Crohn's disease was reported in 70, of which 50 had recurrent episodes (P < 0.0001); 121 of the 234 patients who smoked had recurrence (P = 0.0078); 8% had short symptomatic period (< 24 hours), which was a predisposing factor for recurrence, P < 0.0001. Patients in the non-recurrent group waited 2.53 hours less for surgical intervention (P < 0.0005(. The average time for recurrent episode was 18.95 ± 33.7 months. Fistula was diagnosed in 16.9% of all cases, while 11.6% were within the recurrent group. Surgical expertise of the physician did not significantly change the recurrence rate., Conclusions: Crohn's disease and smoking were the only significant risk factors for recurrence of perianal abscess. Timely intervention and drainage of sepsis should not be delayed. Involvement of more experienced surgeons did not seem to alter the natural history of the disease.

Background: Anal fistula commonly appears after incision and drainage of a perianal abscess. Theoretically, a fistula develops as a consequence of the infection process. Antibiotic treatment was suggested to decrease the possibility of fistula development., Objective: We hypothesized that antibiotic treatment has no influence on the development of anal fistula after surgical treatment of perianal abscess., Design: A single-blinded randomized prospective study., Settings: Patients with primary cryptogenic abscesses were eligible to participate., Patients: Patients were divided into 2 groups. Patients in group I received amoxicillin 875 mg/clavulanic acid 125 mg during 7 days after surgery, and patients in group II received no antibiotics. The study database included demographics and clinical and laboratory data., Main Outcome Measures: Patients were examined in our outpatient clinic 2 weeks, 4 months, and 1 year after surgery, and a telephone questionnaire was performed 6 months after surgery. The primary outcome was the formation of anal fistula. The secondary outcome was recurrent perianal abscess., Results: Overall, 98 patients completed the study. Groups were not different in inclusion. Anal fistula was diagnosed in 16 patients (16.3%) in group I (treatment group) and 10 patients (10.2%) in group II (control group; p = 0.67). Nine patients (9.2%) developed recurrent perianal abscess, 4 in the treatment group and 5 in the control group ( p = 0.73)., Limitations: A relatively small number of patients were treated in a single medical center., Conclusion: Antibiotic therapy has no influence on anal fistula or recurrent perianal abscess formation after incision and drainage of perianal abscess. See Video Abstract ., El Tratamiento Con Antibiticos No Tiene Influencia En La Formacin De Fstula Anal Y En El Absceso Perianal Recurrente Despus De La Incisin Y Drenaje De Un Absceso Perianal Criptognico Un Estudio Prospectivo Aleatorizado, Simple Ciego: ANTECEDENTES:La fístula anal comúnmente aparece después de la incisión y drenaje de un absceso perianal. Teóricamente, la fístula se desarrolla como consecuencia del proceso infeccioso. Se sugirió tratamiento antibiótico para disminuir la posibilidad de desarrollo de fístula.OBJETIVO:Hipotetizamos que el tratamiento con antibióticos no tiene influencia en el desarrollo de fístula anal después del tratamiento quirúrgico del absceso perianal.DISEÑO:Estudio prospectivo, aleatorio, simple ciego.AJUSTE Y PACIENTES:Los pacientes con absceso criptogénico primario fueron elegibles para participar. Los pacientes se dividieron en dos grupos. Los pacientes del Grupo I recibieron amoxicilina 875 mg/ácido clavulánico 125 mg durante los 7 días posteriores a la cirugía y los pacientes del Grupo II no recibieron antibióticos. La base de datos del estudio incluyó datos demográficos, clínicos y de laboratorio.PRINCIPALES MEDIDAS DE RESULTADO:Los pacientes fueron examinados en nuestra clínica ambulatoria 2 semanas, cuatro meses y 1 año después de la cirugía y se realizó un cuestionario telefónico 6 meses después de la cirugía. El resultado primario fue la formación de una fístula anal. El resultado secundario fue el absceso perianal recurrente.RESULTADOS:En total, 98 pacientes completaron el estudio. Los grupos no fueron diferentes en cuanto a la inclusión. Se diagnosticó fístula anal en 16 (16,3%) pacientes del Grupo I (grupo de tratamiento) y 10 (10,2%) pacientes del Grupo II (grupo control) (p = 0,67). Nueve pacientes (9,2%) desarrollaron absceso perianal recurrente, 4 en el grupo de tratamiento y 5 en el grupo control (p = 0,73).LIMITACIONES:Número relativamente pequeño de pacientes tratados en un solo centro médico.CONCLUSIÓN:La terapia con antibióticos no tuvo influencia sobre la fístula anal o la formación de absceso perianal recurrente después de la incisión y drenaje del absceso perianal. (Traducción - Dr. Fidel Ruiz Healy )., (Copyright © The ASCRS 2024.)

Purpose: Perianal fistulae are disabling complications of Crohn's Disease. Magnetic resonance imaging features could predict treatment response. This study aimed to determine which magnetic resonance imaging features were predictive of long-term clinical outcome in real life., Methods: Consecutive patients with magnetic resonance imaging performed in a tertiary center were retrospectively analyzed. Clinical outcome was defined as a need for surgical drainage of perianal fistulae or hospitalization. Clinical data and magnetic resonance imaging features (MAGNIFI-CD and Van Assche indices, degree of fibrosis) were studied., Results: Fifty-two patients were included between 2016 and 2019 with a mean follow-up of 38 months [29;48]. A higher MAGNIFI-CD index (17/25 versus 11/25; p < 0.01) was associated with an unfavorable long-term clinical outcome. The MAGNIFI-CD index showed an area under the curve of 0.74 (p = 0.006) to predict the clinical outcome of perianal Crohn's disease, compared to 0.67 (p < 0.05) for the Van Assche index. At a threshold of 13 for the MAGNIFI-CD index, sensitivity was 75% (CI95% [59%; 86%]) and specificity was 69% (CI95% [44%; 86%]). No association was found between the degree of fibrosis and clinical outcome, but the association of a high degree of fibrosis (≥ 80%) and of a low MAGNIFI-CD index (≤ 13) was predictive of clinical outcome (p < 0.01)., Conclusion: The MAGNIFI-CD index could be used to predict clinical outcome in perianal Crohn's disease. In combination with a high degree of fibrosis, a low MAGNIFI-CD index, may help to identify patients with the best prognosis., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: To observe the clinical efficacy and safety of Yanghe decoction Huacai for the repair of Yin syndrome wounds with slow-healing after anal fistula surgery., Methods: A total of 120 patients with slow-healing negative wounds with after low-grade anal fistula surgery who met the inclusion criteria were divided into a treatment group and a control group based on a random number table method, with 60 patients in the treatment group and 60 patients in the control group. The treatment group was given Yanghe decoction Huacai in combination with routine treatment; the control group was only given routine treatment, in which the wound surface was disinfected with iodine, and then covered with sterile gauze. The course of treatment in both groups was 10 d. After treatment, the wound secretion score, wound granulation tissue score, the expression levels of basic fibroblast growth factor (bFGF), transforming growth factor β1 (TGF-β1), and epidermal growth factor (EGF) in the wound, wound healing time and clinical efficacy were compared., Results: There was no significant difference in age or gender between the two groups ( P > 0.05). On the 10th and 15th days after the surgery, the wound secretion scores were higher in the treatment group than in the control group ( P < 0.01). Comparing the two groups at the 10th and 15th day after surgery, the granulation tissue growth scores in the treatment group were better than the in control group ( P < 0.01). On the 10th and 15th day after operation, the expression levels of bFGF, TGF-β1 and EGF factors in the treatment group were stronger than those in the control group. The healing time of the wounds in the treatment group was significantly shorter than in the control group ( P < 0.01). The clinical efficacy of the two groups after treatment was compared, and the overall efficacy of the treatment group was significantly higher than that of the control group ( P < 0.01)., Conclusions: Yanghe decoction Huacai have significant efficacy in the treatment of slow-healing wounds with Yin syndrome after anal fistula surgery. It improves wound secretions, promotes the growth of wound granulation tissue, and shortens wound healing time. Its mechanism of action may be related to the control of wound inflammation. It is related to increasing the expression of bFGF, TGF-β1 and EGF in wound tissue, and promoting wound angiogenesis and fibroblast proliferation.

Introduction and Hypothesis: Vaginal mesh has been used for years to try to improve the results of pelvic organ prolapse surgery, but current evidence does not confirm this improvement and instead describes serious and frequent adverse events., Clinical Case: 64-year-old patient with rectal extrusion of posterior vaginal mesh placed 8 years earlier, and persistent left ischiorectal fistula refractory to surgery. She required 5 surgeries, carried out jointly between gynecology and general surgery, to solve, firstly, the bilateral perianal abscess secondary to extrusion of the posterior vaginal mesh into the rectum and then the persistent left ischiorectal fistula, despite the removal of the material prosthetic. Finally, the fistula was solved by injection of platelet-rich plasma., Conclusions: Vaginal mesh complications often need a multidisciplinary approach, and treatment may require multiple approaches and more than one surgical procedure. In the case of a persistent fistula refractory to surgery, after removing the mesh, non-invasive regenerative therapies that promote vascular growth and tissue regeneration could be considered such as platelet-rich plasma., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Fistula-tract laser closure (FiLaC™) has shown promising outcomes in perianal fistulizing Crohn's disease (pfCD). However, most studies assessed a mixed cohort encompassing pfCD and cryptoglandular fistulas during a short follow-up period. This study aimed to evaluate the long-term treatment outcomes of FiLaC™ in patients with complex pfCD., Methods: Data from patients with complex pfCD who underwent FiLaC™ during deep remission of Crohn's disease between January 2019 and December 2020 were retrospectively analyzed. Patient demographics, surgery history, and medication strategy were registered before surgery. Follow-ups were scheduled at 1, 2, and 3 months after FiLaC™, and at 2-month intervals thereafter. The primary endpoint was clinic healing, while clinic remission/unhealed/recurrence were classified as unhealed. Additionally, adverse events and Wexner fecal incontinence score were documented., Results: Forty-nine patients (40 men and 9 women) with a median age of 26.0 (19.0-35.5) years were included with a median follow-up of 50.0 (39.5-54.0) months. Of these, 31 (63.3%) patients achieved fistula healing, 3 (6.1%) experienced improvement, 3 (6.1%) remained unhealed, and 12 (24.5%) experienced recurrence. Montreal A category was lower in the healed group (P < 0.001). No major complications, such as bleeding or fecal or urinary incontinence, were observed, and pain was transient. The Wexner incontinence score decreased significantly at the last available follow-up, indicating an intact postoperative continence function (P = 0.014). PCDAI scores were significantly higher in the unhealed group (P = 0.041)., Conclusion: FiLaC™ is an efficient and safe sphincter-saving procedure for patients with complex pfCD., (© 2024. Springer Nature Switzerland AG.)

The perianal disease affects up to one-third of individuals with Crohn's disease (CD), causing disabling symptoms and significant impairment in quality of life, particularly for those with perianal fistulising CD (PFCD). The collaborative effort between gastroenterologists and surgeons is essential for addressing PFCD to achieve fistula closure and promote luminal healing. Limited fistula healing rates with conventional therapies have prompted the emergence of new biological agents, endoscopic procedures and surgical techniques that show promising results. Among these, mesenchymal stem cells injection is a particularly hopeful therapy. In addition to the burden of fistulas, individuals with perianal CD may face an increased risk of developing anal cancer. This underscores the importance of surveillance programmes and timely interventions to prevent late diagnoses and poor outcomes. Currently, there is no established formal anal screening programme. In this review, we provide an overview of the current state of the art in managing PFCD, including novel medical, endoscopic and surgical approaches. The discussion also focuses on the relevance of establishing an anal cancer screening programme in CD, intending to propose a risk-based surveillance algorithm. The validation of this surveillance programme would be a significant step forward in improving patient care and outcomes., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Introduction: Several studies associate the presence of higher serum concentrations of infliximab (IFX) with fistula healing in perianal Crohn's disease (CD). This study aimed to evaluate serum IFX concentrations in patients with perianal fistulizing CD (PFCD) in the presence or absence of general, clinical, and radiological activities., Methods: This was a cross-sectional study in patients with PFCD during maintenance treatment with IFX from two centers. Serum IFX concentrations were measured before their next infusion and anal fistulas were evaluated by clinical examination and magnetic resonance imaging (MRI), whenever possible, performed 90 days before or after serum collection. According to clinical scores, radiological activity, and disease markers, patients were classified as in remission or active disease. Mean serum IFX concentrations were compared between the groups., Results: Thirty-eight patients with PFCD were included. Demographic characteristics were similar in patients with remission or active disease. The overall mean serum IFX concentration of the entire sample (n = 38) was 5.21 ± 4.75 μg/mL (median 3.63; IQR 1.44-8.82). Serum IFX levels were 6.25 ± 5.34 μg/mL (median 3.62; IQR 1.95-11.03) in the 23 (60.5%) patients in remission and 3.63 ± 3.24 μg/mL (median 3.63; IQR 1.32-6.43; p = 0.226) in the 15 (39 .5%) who presented active disease. When evaluating general, clinical, and radiological activity of PFCD, and deep remission in isolation, no statistical difference between the groups was observed (p = 0.226, p = 0.418, p = 0.126, and p = 0.232, respectively). The 13 (34.2%) patients with an optimized dose of IFX had significantly higher serum concentrations than the remaining 25 (65.8%) with a standard dose: 8.33 ± 4.41 μg/mL (median 8.36; IQR 3.82-11.20) vs. 3.59 ± 4.13 μg/mL (median 1.97; IQR 1.18-3.85) -p = 0.002. Patients in remission and with an optimized IFX dose had significantly higher serum IFX concentrations than those with a standard dose (p = 0.006), whereas no significant difference was observed among those with active disease (p = 0.083)., Conclusion: There were no differences in IFX serum concentrations in patients with clinical or radiological active PFCD as compared with those in remission. Patients with an optimized IFX dose had significantly higher serum concentrations than those with a standard dose. Patients in remission and with an optimized IFX dose had significantly higher serum concentrations than those with a standard dose., (© 2024. Springer Nature Switzerland AG.)

Background and Aims: Video-assisted anal fistula treatment (VAAFT) is an innovative surgical approach enabling the direct visualization of the fistula tract structure. This study aims to assess the efficacy of VAAFT in comparison with that of traditional surgical methods and explore potential risk factors contributing to fistula recurrence to provide new recommendations for surgical selection., Materials and Methods: Information was collected from 100 patients with complex anal fistula (CAF) in our hospital who underwent surgical treatment from January 2021 to January 2023. We compared the baseline information and surgical outcomes of two groups, analyzed the risk factors for fistula recurrence by using logistic regression analysis, and conducted further exploration by using the body mass index., Results: Equal numbers of patients underwent VAAFT and traditional surgeries, and no significant differences in baseline information were observed. Patients who received VAAFT experienced less intraoperative bleeding (15.5 (14.0-20.0) vs. 32.0 (25.0-36.0)), shorter hospital stays (2.0 (2.0-2.5) vs. 3.0 (3.0-3.5)), reduced postoperative pain and wound discharge, but longer operative times (43.3 ± 6.9 vs. 35.0 (31.5-40.0)) compared with patients who underwent traditional surgeries. No significant differences in recurrence rates were found three and six months after operation (the p-values were 0.790 and 0.806, respectively). However, the Wexner scores of the VAAFT group were significantly low in the first follow-up (0 (0-1.0) vs. 2.0 (1.0-2.0)). Postoperative recurrence of fistulas may be associated with obesity (p-value = 0.040), especially in patients undergoing traditional surgeries (p-value = 0.036)., Conclusion: VAAFT offers advantages, such as less pain, less trauma, and faster recovery, compared with traditional surgical treatment. Obese patients with CAF are prone to recurrence, and we recommend that they undergo VAAFT treatment rather than traditional surgeries., (© 2024. The Author(s).)

We present a case of a 64-year-old male with a history of perianal abscesses that have been surgically treated on 10 occasions. Eight months after the last drainage procedure, he presented with a new abscess. Drainage was performed, revealing a cavity with smooth walls, a chronic appearance, filled with mucoid material. An internal fistulous opening was identified at the 6 o'clock position above the anorectal line, which communicated with the described cavity, forming a trans-sphincteric fistula to the mid-anal canal. Biopsy with pathological anatomy showed a mucinous adenocarcinoma with possible intestinal origin (CK20+, CDX2+, TTF1-, CK7+). After completing the evaluation, he was diagnosed with T4N1M0 rectal neoplasia. A diverting colostomy was performed, followed by neoadjuvant therapy, and subsequently, a laparoscopic abdominoperineal amputation. Pathological anatomy revealed residual adenocarcinoma ypT2N0 N0V0L0, R0. This case is notable for both the rarity of a mucinous adenocarcinoma originating in a perianal fistula and the nonspecific clinical presentation of such tumors. Clinical suspicion is crucial, especially in cases of recurrent abscesses with the discharge of mucoid material through fistulous openings, prompting the need for biopsies to ensure proper diagnosis and subsequent optimal treatment.

Background: 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)., Objective: Presenting real-world effectiveness data for darvadstrocel in a Spanish population., Design: Observational retrospective cohort study with prospective data gathering., Settings: The study was conducted at 14 institutions in Spain., Patients: 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., Interventions: Darvadstrocel treatment., Main Outcome Measures: 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., Results: 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., Limitations: Retrospective nature of the study., Conclusions: 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 ., Uso De Darvadstrocel Terapia Con Clulas Madre Alognicas Para Fstula En Enfermedad De Crohn En La Prctica Clnica Real El Proyecto Nacional Para Implementar De Clulas Madre Mesenquimales Para El Tratamiento De La Fstula De Crohn Perianal El Estudio Prime: 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 )., (Copyright © The ASCRS 2024.)

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., (© 2024. The Author(s).)

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.

Background and Aims: In this systematic review we summarise existing scoring indices for assessing disease activity and quality of life in perianal fistulising Crohn's disease [PFCD], and highlight gaps in the literature., Methods: MEDLINE, EMBASE, and CENTRAL were searched from August 24, 2022, to identify studies evaluating clinical, radiological, or patient-reported outcome measures [PROMS] in PFCD. The primary objective was to identify all available scoring indices and describe the operating properties of these indices., Results: A total of 53 studies reported on the use of one clinical index [Perianal Disease Activity Index: PDAI], three PROMs, and 10 radiological indices; 25 studies evaluated the operating properties of these indices. The PDAI demonstrated content validity, construct validity, and responsiveness but criterion validity or reliability were not assessed. The Van Assche Index [VAI], modified VAI, and the Magnetic Resonance Index for Assessing Fistulas in Patients with CD [MAGNIFI-CD] were the most studied radiological indices. These indices demonstrated responsiveness and reliability. The VAI and MAGNIFI-CD demonstrated construct validity; criterion and content validity and feasibility have not been assessed. Among the three PROMs, the Crohn's Anal Fistula Quality of Life index demonstrated content and construct validity, inter-observer reliability, and responsiveness; criterion validity, intra-observer reliability, and feasibility have not been assessed for this index., Conclusions: There are no fully valid, reliable, and responsive clinical disease or radiological indices for PFCD. Although the radiological indices demonstrated responsiveness and reliability, well-defined cut-offs for response and remission are lacking. Future research should focus on establishing standardised definitions and thresholds for outcomes., (© The Author(s) 2023. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background and Aims: There is an unmet need in the treatment of perianal fistulising Crohn's disease [PFCD]. This study evaluated the efficacy and safety of the Janus kinase 1 preferential inhibitor, filgotinib, for the treatment of PFCD., Methods: This phase 2, double-blind, multicentre trial enrolled adults with PFCD and prior treatment failure. Participants were randomised [2:2:1] to receive filgotinib 200 mg, filgotinib 100 mg, or placebo, once daily orally for up to 24 weeks. The primary endpoint was combined fistula response (reduction from baseline of at least one draining external opening determined by physical assessment, and no fluid collections >1 cm on pelvic magnetic resonance imaging [MRI]) at Week 24., Results: Between April 2017 and July 2020, 106 individuals were screened and 57 were randomised. Discontinuations were lowest in the filgotinib 200 mg group (3/17 [17.6%] versus 13/25 [52.0%] for filgotinib 100 mg and 9/15 [60.0%] for placebo). The proportion of participants who achieved a combined fistula response at Week 24 was 47.1% (8/17; 90% confidence interval [CI] 26.0, 68.9%) in the filgotinib 200 mg group, 29.2% [7/24; 90% CI 14.6, 47.9%] in the filgotinib 100 mg group, and 25.0% [3/12; 90% CI 7.2, 52.7%] in the placebo group. Serious adverse events occurred more frequently with filgotinib 200 mg (5/17 [29.4%]) than with placebo (1/15 [6.7%]). There were no treatment-related serious adverse events or deaths., Conclusions: Filgotinib 200 mg was associated with numerical reductions in the number of draining perianal fistulas based on combined clinical and MRI findings compared with placebo, and was generally well tolerated [NCT03077412]., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation.)

This systematic review and meta-analysis of nonrandomized studies (NRSs) aimed to evaluate the clinical efficacy and safety of two types of surgical interventions (respectively drainage alone and drainage with primary fistula treatment) for perianal abscesses (PAs) in children. Studies from 1992 to July 2022 were searched in 10 electronic databases. All relevant NRSs with available data which compared surgical drainage with or without primary fistula treatment were included. Patients with underlying diseases which led to abscess formation were excluded. The Newcastle-Ottawa Scale was used to assess the risk of bias and quality of the included studies. The outcomes were the healing rate, fistula formation rate, fecal incontinence, and wound healing duration. A total of 16 articles with 1,262 patients were considered suitable for the final meta-analysis. Primary fistula treatment was associated with a significantly higher healing rate when compared with incision and drainage alone (odds ratio [OR]: 5.76, 95% confidence interval [CI]: 4.04-8.22). This aggressive procedure for PA resulted in an 86% reduction in the fistula formation rate (OR: 0.14, 95% CI: 0.06-0.32). Limited data showed patients who underwent primary fistula treatment have a minor effect on postoperative fecal incontinence. Primary fistula treatment demonstrates a better clinical efficacy in promoting the healing rate and decreasing the formation of fistulas in PAs in children. The available evidence for a minor impact on anal function after this intervention is less strong., Competing Interests: None declared., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Introduction: Pediatric patients with perianal Crohn's Disease (CD) suffer recalcitrant fistulas, abscesses, and strictures. Fecal diversion is a palliative last resort, but the expected clinical course and long-term management of the ostomy for this population is unclear. We sought to identify factors predictive of ostomy takedown and establish management recommendations for fistulizing and stenosing disease., Methods: We reviewed our institutional registry for patients aged 1-18 years with CD who received perianal surgery from 2011 to 2021. We analyzed medical therapy, examinations under anesthesia (EUA), fistula and stenosis response, and rates of fecal diversion and reversal., Results: There were 109 patients with fistulizing CD and 21 with stenosing CD. There were 8 diverted for fistula and 4 due to stricture [8/109 (7 %) vs 4/21 (19 %), p = 0.213]. Three patients with fistulizing disease had their ostomy reversed at an average of 1.46 years. Each demonstrated consistent CD control and with no additional perianal flares. The remainder have been diverted 3.15 ± 4.57 years with 2.1 ± 2.8 EUAs. Only one patient with stricture was durably reversed, but they still require serial anal dilation. Two were reversed but required re-diversion due to stricture progression., Conclusion: Reversal rates after fecal diversion for pediatric perianal CD remain disappointingly low and diversion does not obviate the possibility of future EUAs. While reversal was successful for medically responsive patients with fistulizing disease, those with stenosing disease remained dependent on anal dilations and were more likely to fail reversal. Fecal diversion does nothing to reverse an established stricture and such patients will likely need to decide between indefinite dilations or permanent ostomy., Level of Evidence: IV., Type of Study: Retrospective review., Competing Interests: Conflicts of interest The authors have no competing interests to declare. No financial support has been provided for this research., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Limited data are available regarding the risk factors for fistula-in-ano (FIA) in infants and toddlers, potentially affecting their daily lives., Objectives: The purpose of this study was to identify potential risk factors for FIA in infants and toddlers, in order to implement early preventive interventions, avoid disease progression, and develop therapeutic strategies., Design and Settings: A retrospective case-control study was conducted, comparing 41 infants and toddlers diagnosed with FIA with 41 healthy controls, between August 2020 and December 2021., Independent Variables: (a) maternal characteristics during pregnancy and delivery, (b) perinatal characteristics, dietary behaviors, and defecation-related behaviors in infants and toddlers, (c) family dietary behaviors., Results: Mothers of infants and toddlers with FIA had given birth more times in the past, while the infants and toddlers themselves had less mealtime, a higher rate of exclusive breastfeeding, frequent loose stools, and a larger proportion of used wipes, experiencing perianal skin anomalies. The logistic regression analysis revealed that there are four significant risk factors associated with the development of FIA in infants and toddlers, including the number of previous deliveries by the mother (OR 6.327), defecation frequency score (OR 5.351), stool consistency score (OR 5.017), and cleaning with wipes after defecation (OR 8.089)., Conclusion: Based on our data, it appeared that FIA in infants and toddlers could be attributed to several factors. These included an increased number of previous deliveries by mothers, frequent loose stools, and repeated wipe use. To prevent the occurrence and worsening of the disease, it is important to improve the frequency and consistency of stooling and provide proper care. Further research is required to verify these findings in other clinical settings., (© 2024. The Author(s).)

Background: Perianal fistulas (PF) affect one-third patients with Crohn's disease (CD) with limited therapeutic options. There is dearth of literature on safety and efficacy of bone marrow-derived mesenchymal stromal cells (BMSCs) in this population., Methods: An open-label, phase I/II, single-arm study was conducted involving local administration of human allogeneic bone marrow-derived mesenchymal stromal cells in perianal fistula of patients with Crohn's disease refractory to standard therapies. Clinical severity and biomarkers were assessed at baseline and periodically until week 104 , and MRI at week 24 and 104. Primary and secondary objectives were to assess safety and efficacy respectively. Fistula remission was complete closure of fistula openings with < 2 cm perianal collection on MRI, and fistula response was decrease in drainage by ≥ 50%. Change in perianal disease activity index, quality-of-life and Van Assche index on MRI over time was assessed using mixed-effect linear regression model., Results: Ten patients (male:8, mean age:27.4 ± 12.0years) were recruited. Self-resolving procedure-related adverse events occurred in three patients, with no follow-up adverse events. In intention to treat analysis at week 24, two patients (20%) achieved fistula remission and seven (70%) had fistula response. At week 52, two (20%) patients were in remission and seven (70%) maintained response. At 104 weeks, two (20%) patients maintained response and one (10%) was in remission. Statistically significant decrease in perianal disease activity index (P = 0.008), Van Assche Index (P = 0.008) and improvement in quality-of-life (P = 0.001) were observed over time., Conclusions: Allogeneic BMSCs are safe and effective for the treatment of perianal fistulizing CD with significant improvement in clinical severity and radiological healing., Trial Registration: The study was prospectively registered on Clinical trials registry - India (CTRI), CTRI/2020/01/022743 on 14 January 2020, http://ctri.nic.in ., (© 2024. The Author(s).)

The efficacy of surgical intervention for perianal infection in patients with hematologic malignancies is not well established. Therefore, our study aimed to investigate the clinical efficacy and complications of surgical treatment of perianal infection in patients with hematologic malignancies. This retrospective study included patients with hematological malignancies who were diagnosed with perianal infections and treated at the China Aerospace Science & Industry Corporation 731 Hospital between 2018 and 2022. Patient characteristics, hematological data, surgical intervention, and complications, including recurrence and mortality, were analyzed. This study included 156 patients with leukemia aged 2 months to 71 years who were treated surgically for perianal infection, comprising 94 males and 62 females. Perianal infection included 36 cases of abscesses, 91 anal fistulas, and 29 anal fissures accompanied by infection. A total of 36 patients developed severe complications postoperatively, including 4 patients who died, 6 patients with severe incision bleeding, 18 patients with severe pain, 6 patients with sepsis, 12 patients who needed reoperation, 15 patients with hospitalization for more than 2 weeks, and 3 patients with anal stenosis; none of the patients developed anal incontinence. Additionally, risk factors for postoperative complications of perianal infection in patients with hematologic malignancies include leukopenia, agranulocytosis, thrombocytopenia, depth of abscess and not undergone an MRI. Surgical intervention may improve the prognosis of patients with perianal abscess formation, particularly in patients who show no improvement with medical therapy and those who develop perianal sepsis. Granulocytopenia and thrombocytopenia should be improved before surgery, which can significantly reduce postoperative complications. Although these findings are from a case series without a comparator, they may be of value to physicians because to the best of our knowledge, no randomized or prospective studies have been conducted on the management of perianal infections in patients with hematological malignancies., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background/aims: A poor prognostic factor for Crohn's disease (CD) includes perianal fistulizing disease, including perianal fistula and/or perianal abscess. Currently, a tool to assess perianal symptoms in patients with CD remains nonexistent. This study aimed to develop a perianal fistulizing disease self-screening questionnaire for patients with CD., Methods: This prospective pilot study was conducted at three tertiary referral centers between January 2019 and May 2020. We formulated questions on perianal symptoms, including tenesmus, anal discharge, bleeding, pain, and heat. A 4-point Likert scale was used to rate each question. Patients with CD completed a questionnaire and underwent pelvic magnetic resonance imaging (MRI)., Results: Overall, 93 patients were enrolled, with 51 (54.8%) diagnosed with perianal fistulizing disease, as determined by pelvic MRI. The Spearman correlation findings demonstrated that anal pain (p = 0.450, p < 0.001) and anal discharge (p = 0.556, p < 0.001) were the symptoms that most significantly correlated with perianal disease. For anal pain and discharge, the area under the receiver operating characteristic curve of the scores was significantly higher than that of the combined score for all five symptoms (0.855 vs. 0.794, DeLong's test p = 0.04). For the two symptoms combined, the sensitivity, specificity, and positive predictive and negative predictive values were 88.2, 73.8, 80.4, and 83.8%, respectively, with 81.7% accuracy for detecting perianal fistulizing disease., Conclusion: This study indicates that simple questions regarding anal pain and discharge can help accurately identify the presence of perianal fistulizing disease in patients with CD.

Background: The use of mesenchymal stem cells is considered a novel and promising therapeutic option for patients with perianal fistulizing Crohn's disease; however, data on its clinical application remain scarce. This multicenter nationwide study aimed to assess the clinical efficacy of mesenchymal stem cells in closing complex anal fistulas., Methods: In this study 14 Crohn's disease patients (3 males, 11 females) with complex anal fistulas treated in 3 tertiary hospitals in Austria were included between October 2018 and April 2021. Injection of 120 million allogeneic expanded adipose-derived mesenchymal stem cells (Cx601-darvadstrocel) was performed in each patient. Closure of the external fistula opening without secretion by external manual compression was defined as treatment success., Results: The median age of the patient population at the time of surgery was 32 years (range 26-53 years) with a median body mass index of 21.7 kg/m 2 (range 16.7-26.6 kg/m 2 ). Of the patients 12 (86%) received monoclonal antibodies (infliximab, adalimumab, ustekinumab, vedolizumab) at the time of surgery. The median number of complex fistulas was 1.4 (range 1-2), The median operative time was 20 min (range 6-50 min) with no perioperative complications. After a median follow-up of 92 weeks, we found successful fistula closure in 57.1% (n = 8) of treated patients. The perianal disease activity index did not improve significantly from initially 7 to a median of 6 after 52 weeks (p = 0.495)., Conclusion: Darvadstrocel is a safe, minimally invasive surgical technique without significant perioperative complications. Clinical success can be expected in about half of the treated patients., (© 2023. The Author(s).)

Background: Fistulas are a debilitating complication of Crohn's disease [CD]. We conducted a systematic review to assess the efficacy of medical therapies for fistulizing CD., Methods: MEDLINE, Embase, and CENTRAL were searched on May 26, 2022, for randomized controlled trials [RCTs] of pharmacological therapy in adults with fistulizing CD. The primary outcome was induction and maintenance of fistula response. Pooled risk ratios [RRs] and 95% confidence intervals [CIs] were calculated. GRADE was used to assess the certainty of evidence., Results: Thirty-eight RCTs were included. Nineteen trials [50%] exclusively involved perianal fistula. The remaining studies included some participants with non-perianal fistula. Pooled RRs for anti-tumour necrosis factor [TNF] agents were not statistically significant for induction [RR 1.36, 95% CI 0.97-1.91] or maintenance of fistula response [RR 1.48, 95% CI 0.97-2.27]. However, in a sensitivity analysis of studies with fistula response as the primary outcome, anti-TNFs were superior to placebo for induction [RR 1.94, 95% CI 1.10-3.41] and maintenance [RR 1.88, 95% CI 1.23-2.88] of fistula response. Oral small molecules [RR 2.56, 95% CI 1.18-5.53] and mesenchymal stem cell [MSC] therapy [RR 1.26, 95% CI 1.01-1.57] were effective for induction of fistula response. Ustekinumab was associated with maintenance of fistula response [RR 1.80, 95% CI 1.04-3.11]. Vedolizumab was not superior to placebo. The certainty of evidence ranged from very low to moderate., Conclusion: Very low- to moderate-certainty evidence suggests that anti-TNF therapy, oral small molecules, ustekinumab, and MSCs are effective for perianal fistulizing CD. Dedicated fistula studies evaluating biologics and small molecules are needed., (© The Author(s) 2023. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

&lt;b&gt;Indroduction:&lt;/b&gt; Cryptoglandular perianal fistula represents a prevalent benign anorectal condition, primarily addressed through surgical interventions, occasionally posing considerable therapeutic challenges. The associated decline in patient quality of life underscores the significance of effective management. However, the lack of a fully understood pathogenesis complicates the treatment approach. Recent research has proposed the involvement of adipose fat tissue in the inflammatory response and pathogenesis of cryptoglandular anal fistula.&lt;b&gt;Aim:&lt;/b&gt; The study aims to characterize the role of adipose fat tissue in the pathogenesis of cryptoglandular anal fistula, with a specific focus on understanding the potential involvement of proinflammatory cytokines in the development of chronic inflammation.&lt;b&gt;Materials and methods:&lt;/b&gt; This study involved the characterization of serum levels of inflammatory cytokines and adipose tissue hormones. A total of 35 samples from both simple and complex cryptoglandular perianal fistula cases were collected during surgical procedures.&lt;b&gt;Results:&lt;/b&gt; Serum levels of leptin, resistin, IL-1β, and IL-8 were significantly elevated in patients operated on due to complex cryptoglandular perianal fistula when compared to patients with simple fistula. Adiponectin was significantly lowered in samples from complex perianal fistula in comparison to simple fistula.&lt;b&gt;Conclusions:&lt;/b&gt; Complex perianal cryptoglandular fistula has a reduced level of anti-inflammatory adipokines i.e. adiponectin, and an increased level of proinflammatory resistin, leptin, IL-1β, and IL-8.

Introduction: Treatment of complex perianal fistulas in Crohn's disease remains a challenge especially after the failure of Infliximab., Aim: Update on the different therapeutic alternatives for anal fistula in Crohn's disease after failure of Infliximab., Methods: 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., Results: 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., Conclusion: Anal fistulas in Crohn's disease are a real therapeutic challenge. New medical and surgical therapies are currently being evaluated, with promising results.

Background: Anal fistula and perianal abscess are commonly acquired anorectal pathologies in children. Surgical treatment options commonly adopted are fistulotomy, fistulectomy, cutting seton placement, and more recently video-assisted anal fistula treatment (VAAFT). Optimal postoperative wound dressing remains debated. This study aimed to report our series of pediatric patients, who received VAAFT and postoperative wound dressing using ozonide oil., Methods: All patients who underwent VAAFT between August 2018 and May 2023 were included in the study. Demographics, clinical features, pre-operative imaging, surgical details, outcome, and mid-term outcome data were retrospectively reviewed for each patient. All VAAFT procedures were performed under general anesthesia and using a 10-Ch fistuloscope., Results: Thirty-three VAAFT procedures were performed in 30 patients over the study period. The median patient age was 5.7 years (range 1.75-14). Anal fistula was idiopathic in 26/30 (86.6%), iatrogenic in 2/30 (6.7%), and secondary to Crohn's disease in 2/30 (6.7%). The median duration of surgery was 23 min (range 18-40). All patients received ozonide oil dressing twice a day for 5 weeks postoperatively. The median hospital stay was 24 h (range 9-36). The median healing time was 28 days (range 17-39). With a median follow-up of 2 years (range 0.5-5), disease recurrence occurred in 3/30 (10%) patients with idiopathic fistula, who were re-operated using the same technique, with no further recurrence. No fecal incontinence or soiling was observed., Conclusion: Our series confirmed that VAAFT is a safe and effective technique to treat children with perianal fistula. The technique is versatile, allowing to treat fistulae of different etiologies. Postoperative course was painless and fast. Future comparative prospective studies are needed to better establish these conclusions., (© 2024. The Author(s).)

Background: Mesenchymal stem cells have been administered via direct injection to treat perianal Crohn's fistulizing disease. We herein sought to determine the safety and durability of treatment response to 12 months with 3 individual phase IB/IIA clinical trials of mesenchymal stem cells for refractory perianal, rectovaginal, and ileal pouch fistulas in the setting of Crohn disease., Methods: Three phase IB/IIA randomized placebo-controlled single-blinded clinical trials were performed for (1) perianal fistulas, (2) rectovaginal fistula, and (3) ileal pouch in situ with anovaginal and/or perianal fistulas. Bone marrow-derived mesenchymal stem cells (75 million in 7.5 mL) were injected at the time of exam under anesthesia on day 0 and month 3. Outcome measures were adverse events and combined clinical and pelvic magnetic resonance imaging healing at month 6 and month 12., Results: Across all 3 trials, 64 patients were enrolled; 49 were treatment and 15 were control. At 6 months, combined clinical and radiographic healing was achieved in 83.3%, 33.3%, and 30.8% of the perianal, rectovaginal, and pouch fistula treatment cohorts, respectively. At 12 months, the treatment response was durable, with 67.7% of perianal, 37.5% of rectovaginal, and 46.2% of peripouch fistulas maintaining complete clinical and radiographic healing. Two patients in the perianal fistula control cohort achieved combined clinical and radiographic healing at 12 months, whereas 0% of rectovaginal and pouch control patients healed., Conclusion: Bone marrow-derived mesenchymal stem cells offer a safe and effective alternative treatment approach for severe perianal, rectovaginal, and peripouch fistulizing Crohn's disease. Treatment results are durable at 12 months., (Copyright © 2023 Elsevier Inc. All rights reserved.)