TOpCLASS Expert Consensus Classification of Perianal Fistulizing Crohn's Disease: A Real-World Application in a Serial Fistula MRI Cohort.

BACKGROUND AND AIMS: Perianal fistulizing 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 that seeks to unify disease severity with patient-centered goals but has not yet been validated. We aimed to apply this to a real-world cohort and 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 (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 which 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. 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 modeling 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.

Multimodal single-cell analyses reveal mechanisms of perianal fistula in diverse patients with Crohn's disease.

BACKGROUND: Crohn's disease complicated by perianal fistulae is more prevalent and severe in patients of African ancestry. METHODS: We profiled single cells from diverse patients with Crohn's disease with perianal fistula from colorectal mucosa and fistulous tracts. Immunofluorescence was performed to validate predicted cell-cell interactions. Unstimulated monocytes were chronically cultured in diverse cohorts. A subset was analyzed by single-nucleus RNA + ATAC sequencing. FINDINGS: Fistulous tract cells from complete proctectomies demonstrated enrichment of myeloid cells compared to paired rectal tissues. Ligand-receptor analysis highlights myeloid-stromal cross-talk and cellular senescence, with cellular co-localization validated by immunofluorescence. Chitinase-3 like-protein-1 (CHI3L1) is a top upregulated gene in stromal cells from fistulae expressing both destructive and fibrotic gene signatures. Monocyte cultures from patients of African ancestry and controls demonstrated differences in CHI3L1 and oncostatin M (OSM) expression upon differentiation compared to individuals of European ancestry. Activating protein-1 footprints are present in ATAC-seq peaks in stress response genes, including CHI3L1 and OSM; genome-wide chromatin accessibility including JUN footprints was observed, consistent with reported mechanisms of inflammatory memory. Regulon analyses confirm known cell-specific transcription factor regulation and implicate novel ones in fibroblast subsets. All pseudo-bulked clusters demonstrate enrichment of genetic loci, establishing multicellular contributions. In the most significant African American Crohn's genetic locus, upstream of prostaglandin E receptor 4, lymphoid-predominant ATAC-seq peaks were observed, with predicted RORC footprints. CONCLUSIONS: Population differences in myeloid-stromal cross-talk implicate fibrotic and destructive fibroblasts, senescence, epigenetic memory, and cell-specific enhancers in perianal fistula pathogenesis. The transcriptomic and epigenetic data provided here may guide optimization of promising mesenchymal stem cell therapies for perianal fistula. FUNDING: This work was supported by grants U01DK062422, U24DK062429, and R01DK123758.

Multicenter registry of pediatric inflammatory bowel disease from a developing country.

BACKGROUND: Despite the rising incidence of pediatric inflammatory bowel disease (PIBD) globally, multicenter collaborative studies of PIBD children among developing countries remain sparse. We therefore aimed to define the initial presentation and short-term outcomes of Thai children with PIBD from a multicenter registry. METHODS: Four teaching hospitals participated in this study. A diagnosis of PIBD requires gastrointestinal endoscopy and histopathology in children aged < 19 years. Besides demographics, we collected clinical information and treatment with the data at 1-year follow up. RESULTS: We included 35 Crohn's disease (CD), one IBD-unclassified, and 36 ulcerative colitis (UC) children (total n = 72 with 60.6% males). The mean age at diagnosis was 7.9 years (SD 4.1) with 38% being very early onset IBD (VEO-IBD). When compared with UC, the CD children were more likely to exhibit fever (42.3 vs. 13.9%), weight loss/failure to thrive (68.6 vs. 33.3%), and hypoalbuminemia (62.9 vs. 36.1%) but less likely to have bloody stools (51.4 vs. 91.7%) (all P < 0.05). No significant differences in demographics, clinical data and medications used with regards to VEO-IBD status. At 1 year after diagnosis (n = 62), 30.7% failed to enter clinical remission and 43.7% remained on systemic corticosteroids. Diarrhea (OR 9.32) and weight issues (OR 4.92) at presentation were independent predictors of failure to enter clinical remission; and females (OR 3.08) and CD (vs. UC) (OR 3.03) were predictors of corticosteroids use at 1-year follow-up. CONCLUSIONS: A high proportion of VEOIBD is noted, and CD was more likely to present with significant inflammatory burden. Diarrhea and weight issues at presentation were independent predictors of failure to enter clinical remission; and females and CD (vs. UC) were predictors of corticosteroids use at 1-year follow-up.

Longitudinal evaluation of the cutaneous and rectal microbiota of German shepherd dogs with perianal fistulas undergoing therapy with ciclosporin and ketoconazole.

BACKGROUND: Perianal fistulas are painful ulcers or sinus tracts that disproportionately affect German shepherd dogs and are proposed as a spontaneous animal model of fistulising Crohn's disease. OBJECTIVES: To characterise the rectal and cutaneous microbiota in German shepherd dogs with perianal fistulas and to investigate longitudinal shifts with lesion resolution during immunomodulatory therapy. ANIMALS: Eleven German shepherd dogs with perianal fistulas and 15 healthy German shepherd dogs. MATERIALS AND METHODS: Affected dogs were evaluated and swabbed at three visits, 30 days apart, while undergoing treatment with ciclosporin and ketoconazole. Healthy German shepherd dogs were contemporaneously sampled. Sites included the rectum, perianal skin and axilla. The microbiome was evaluated following sequencing of the V4 hypervariable region of the 16S ribosomal RNA (rRNA) gene. RESULTS: Alpha diversity was not significantly different between healthy and affected dogs at each of the three body sites (p > 0.5), yet rectal and perianal beta diversities from affected dogs differed significantly from those of healthy dogs at Day 0 (p = 0.004). Rectal and perianal relative abundance of Prevotella spp. increased and perianal Staphylococcus spp. relative abundance decreased in affected dogs over time, coincident with lesion resolution. CONCLUSIONS AND CLINICAL RELEVANCE: Changes in lesional cutaneous and rectal microbiota occur in German shepherd dogs with perianal fistulas and shift over time with lesion resolution during immunomodulatory therapy. Further investigations of the role of cutaneous and enteric microbiota in the pathogenesis of perianal fistulas, and whether manipulation of microbial populations may ameliorate disease, are needed.

Current update on the role of endoanal ultrasound: a primer for radiologists.

Endoanal ultrasound (EAUS) is a valuable imaging modality for the evaluation of anal and perianal pathologies. It provides detailed information about the anatomy and physiology of the anorectal region and has been used in pre-and post-operative settings of anorectal pathologies. EAUS is not only useful in the evaluation of benign pathologies but also in loco-regional staging of anal and rectal tumors. EAUS has several advantages over MRI, including reduced cost, better patient tolerance, and improved scope of application in patients with contraindications to MRI. Despite its benefits, EAUS is not widely performed in many centers across the globe. This article aims to educate radiologists, trainees, and surgeons about the indications, contraindications, patient preparation, imaging technique, and findings of EAUS. We will also highlight the technical difficulties, diagnostic challenges, and procedural complications encountered during EAUS, along with a comparative analysis of EAUS with other imaging approaches.

Does combined medical and surgical treatment improve perianal fistula outcomes in patients with Crohn's disease? A systematic review and meta-analysis.

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-TNF therapy (combined therapy) vs. either therapy alone. METHODS: MEDLINE, EMBASE, and Cochrane databases were searched systematically through December 2023. Surgical intervention was defined as an exam under anesthesia ± setons. We calculated weighted risk ratios (RR) with 95% confidence intervals (CI) 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 (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.

Comparing the Efficacy of a Combination of Diffusion-Weighted Imaging and T2-STIR (Short Tau Inversion Recovery) Imaging With Contrast-Enhanced MRI in the Evaluation of Perianal Fistula.

BACKGROUND: Perianal fistula is clinically diagnosed and commonly characterized using magnetic resonance imaging (MRI). Diffusion-weighted imaging (DWI) and T2-weighted imaging are emerging techniques that can obviate the need for contrast injection in cases where contrast administration is not feasible or contraindicated. The main objective of our study was to compare the efficacy of the combination of DWI and T2 STIR (short tau inversion recovery) imaging with contrast-enhanced MRI for the diagnosis and characterization of perianal fistula. METHODS: Sixty-nine patients with clinical perianal fistula with at least one external opening were evaluated with DWI, T2 STIR, and contrast MRI. A comparative cross-sectional study was conducted in the Department of Radiodiagnosis and Imaging, All India Institute of Medical Sciences, Bhopal, India. The chi-square test was done to find the association between categorical variables. The Kappa test was done to estimate the agreement between two different tests in measuring the outcome. The validity of tests was measured using sensitivity, specificity, positive predictive value, negative predictive value, and accuracy. RESULTS: The combination of DWI and T2 STIR is equivalent to contrast-enhanced MRI in the evaluation of primary and complicated perianal fistula. The combination of DWI and T2 STIR is superior to DWI alone in the classification and characterization of perianal fistula. However, DWI is superior to T2 STIR in differentiating perianal inflammation with abscess from perianal inflammation without abscess and can be used as an alternative to post-contrast fat-suppressed T1-WI in the detection of perianal abscesses and disease activity. CONCLUSION: DWI can be used as an adjunct to T2 STIR, and the combination of DWI and T2 STIR can replace the post-contrast fat-suppressed T1 MRI sequence in the classification and characterization of perianal fistula.

Understanding the role of the primary care physician in the management of patients with Crohn's perianal fistulas.

OBJECTIVES: To understand the role of primary care physicians (PCPs) in the recognition, diagnosis, and management of Crohn's perianal fistulas (CPF) and their referral patterns and treatment expectations. METHODS: This survey-based study was conducted between September 2020 and October 2020. US-based PCPs managing at least one patient with Crohn's disease per week were included. Participants were presented with two case vignettes relevant to primary care practice; Case Vignette 1 comprised three parts and focused on initial CPF presentation and progression to partial response; Case Vignette 2 focused on recurrent CPF. Survey questions elicited the physician's clinical approach to each case. Data were presented as descriptive statistics. RESULTS: Overall, 151 PCPs (median 23 years in practice) who saw about three patients per month with new/existing CPF responded. For Case Vignette 1, upon identification of a fistulous tract, 89% of respondents would refer the patient, mostly to a colorectal surgeon or gastroenterologist. Most PCPs (69%) would begin the patient on medication; 46% would conduct a diagnostic/imaging study. Treatment expectations after referral varied: 55% of respondents believed surgeons would place a seton or use one prior to surgery; 23% expected medical management only; 23% were unsure. Case Vignette 2 revealed that 98% of PCPs preferred to be involved in patient care after referral; however, only 49% were. Of these, 76% considered reinforcing patient treatment adherence as their primary role. While 80% of PCPs were at least moderately satisfied with communication and care coordination with multidisciplinary teams, 52% considered lack of access to specialists as at least a moderate barrier to multidisciplinary team management. CONCLUSION: PCPs want more involvement in multidisciplinary management of patients with CPF. Continuing education providing PCPs with up-to-date information on diagnostic modalities, treatment options, early diagnosis, the role of PCPs within a multidisciplinary team, and effective initial CPF care is required.

What were the study's aims?To understand how primary care physicians recognize, treat, and monitor patients with Crohn's disease-related perianal fistulas (small tunnels between the bowel and skin near the anus).How was the study done?US-based primary care physicians, including internists, were included if they had experience in treating patients with Crohn's disease. Descriptions of the history and symptoms of two hypothetical patients were provided: one patient who may have Crohn's perianal fistulas and another patient whose Crohn's perianal fistulas had returned after being treated. After reading these descriptions, the physicians completed a questionnaire designed to show how they would help each patient.What did the study find out?Not all physicians treat patients with Crohn's perianal fistulas in the same way in terms of diagnostic tests and medical treatments, although most said they would refer them to a specialist if a fistula was identified. Many wanted to be involved in patient care after referral to a specialist but only half were. Of those, most thought their main role was to ensure patients followed the treatments given by specialists. More than half of primary care physicians thought a lack of access to specialists could be a barrier to care.How does this impact care?The physicians surveyed want more involvement in multidisciplinary teams who look after patients with Crohn's perianal fistulas. To do this, they need more education about the diagnosis and treatment of Crohn's perianal fistulas, and clarity around their role within multidisciplinary teams who manage these patients.

Perianal fistulizing Crohn's disease: Current perspectives on diagnosis, monitoring and management with a focus on emerging therapies.

Crohn's disease (CD), a chronic inflammatory bowel disorder, manifests in various phenotypes, with fistulizing perianal CD (CD-PAF) being one of its most severe phenotypes. Characterized by fistula formation and abscesses, CD-PAF impacts 17% to 34% of all CD cases and with a significantly deleterious impact on patient's quality of life, while increasing the risk for anorectal cancers. The pathogenesis involves a complex interplay of genetic, immunological and environmental factors, with cytokines such as tumor necrosis factor-alpha (TNF-α) and transforming growth factor-beta (TGF-ß) playing pivotal roles. Diagnostic protocols require a multi-disciplinary approach including colonoscopy, examination under anesthesia and magnetic resonance imaging. In terms of treatment, biologics alone often prove inadequate, making surgical interventions such as setons and fistula surgeries essential. Emerging therapies such as mesenchymal stem cells are under study. The South Asian context adds layers of complexity, including diagnostic ambiguities related to high tuberculosis prevalence, healthcare access limitations and cultural stigma toward perianal Crohn's disease and ostomy surgery. Effective management necessitates an integrated, multi-disciplinary approach, especially in resource-constrained settings. Despite advances, there remain significant gaps in understanding the disease's pathophysiology and a dearth of standardized outcome measures, underscoring the urgent need for comprehensive research.

Evaluation surgical strategies in perianal fistulas treatment: Efficacy draining seton compared to other surgical approaches; a case-control study.

Background and Aims: Perianal fistula is a prevalent anorectal condition originating from an infectious crypt extending to the external opening. Multiple surgical methods exist for treating perianal fistulas; however, selecting the appropriate options is still controversial. Our study aims to evaluate seton replacement versus other surgical methods in treating perianal fistula. Methods: This study recruited 72 patients presenting with perianal discharge and diagnosed with perianal fistula through intra-sphincteric, trans-sphincteric, and supra-sphincteric examinations at Imam Reza and Besat Hospitals from July 2022 up to March 2023. Regarding case-control design, patients were divided into two groups: the first group (n = 36) underwent seton insertion, while the control group (n = 36) received alternative surgical methods. Follow-up was conducted for 1 month post-discharge, with monthly visits for 6 months. Patients were evaluated for fistula tract healing, seton loosening, and daily secretion rate (based on infected pads) during each visit. Finally, the two groups were compared in terms of improvement rates. Results: In the seton group, approximately 94.4% of patients showed improvement. However, the difference between the groups was insignificant (p = 0.494). Seton replacement was performed in 52% of patients, with the majority requiring replacement twice (61%). Improvement rates were highest among cases with two seton replacements, although the difference was not statistically significant (p = 0.073). Following seton replacement, the most common treatment methods were endoanal flap and fistulotomy, with observed improvement in 10 cases for each procedure. Conclusion: This study highlights that draining seton remains a primary choice for intermediate treatment due to its satisfactory improvement rate and lower requirement for replacement, especially up to two times.

Can Short Tau Inversion Recovery (STIR) Imaging Be Used as a Stand-Alone Sequence To Assess a Perianal Fistulous Tract on MRI? A Retrospective Cohort Study Comparing STIR and T1-Post Contrast Imaging.

INTRODUCTION: Perianal fistulas demand precise preoperative assessment for optimal surgical outcomes. MRI, using Short Tau Inversion Recovery (STIR) and T1-post contrast sequences, plays a crucial role in this evaluation.This retrospective cohort study compared STIR imaging's diagnostic efficacy with T1-post contrast sequences in identifying perianal fistulous tracts. The study investigated whether STIR imaging could serve as the sole diagnostic sequence, simplifying clinical practice. METHODS: In a tertiary care hospital, 100 patients underwent pelvic MRI for suspected perianal fistulas. Radiologists independently evaluated STIR and T1-post contrast sequences for internal openings, tract extent, distinction, abscess presence, and tract type. Sensitivity, specificity, area under the curve (AUC), and Cohen's kappa analysis were used for diagnostic assessment. RESULTS: STIR imaging showed notable sensitivity (79.8-97.9%) and specificity (100%) for identifying internal openings and tracts. Combined with T1-post contrast, diagnostic accuracy improved significantly, with near-perfect AUC values. Kappa values indicated moderate to substantial agreement between radiological assessments and clinical diagnosis. The combined sequences achieved 100% sensitivity and specificity for tract visualization. CONCLUSION: STIR imaging presents promise as a singular diagnostic tool for perianal fistulas, especially when combined with T1-post contrast sequences. While offering potential clinical diagnosis simplifications, further studies are warranted to validate its utility and ensure comprehensive diagnostic accuracy.

Role of Adipose Tissue Hormones in Pathogenesis of Cryptoglandular Anal Fistula.

The cryptoglandular perianal fistula is a common benign anorectal disorder that is managed mainly with surgery and in some cases may be an extremely challenging condition. Perianal fistulas are often characterized by significantly decreased patient quality of life. Lack of fully recognized pathogenesis of this disease makes it difficult to treat it properly. Recently, adipose tissue hormones have been proposed to play a role in the genesis of cryptoglandular anal fistulas. The expression of adipose tissue hormones and epithelial-to-mesenchymal transition (EMT) factors were characterized based on 30 samples from simple fistulas and 30 samples from complex cryptoglandular perianal fistulas harvested during surgery. Tissue levels of leptin, resistin, MMP2, and MMP9 were significantly elevated in patients who underwent operations due to complex cryptoglandular perianal fistulas compared to patients with simple fistulas. Adiponectin and E-cadherin were significantly lowered in samples from complex perianal fistulas in comparison to simple fistulas. A negative correlation between leptin and E-cadherin levels was observed. Resistin and MMP2 levels, as well as adiponectin and E-cadherin levels, were positively correlated. Complex perianal cryptoglandular fistulas have a reduced level of the anti-inflammatory adipokine adiponectin and have an increase in the levels of proinflammatory resistin and leptin. Abnormal secretion of these adipokines may affect the integrity of the EMT in the fistula tract. E-cadherin, MMP2, and MMP9 expression levels were shifted in patients with more advanced and complex perianal fistulas. Our results supporting the idea of using mesenchymal stem cells in the treatment of cryptoglandular perianal fistulas seem reasonable, but further studies are warranted.

Quantifying 18F-Fluorodeoxyglucose Uptake in Perianal Fistulas on PET/CT: A Retrospective Analysis.

RATIONALE AND OBJECTIVES: The use of 18F-fluorodeoxyglucose positron emission tomography-computed tomography (FDG-PET/CT) in assessing inflammatory diseases has shown significant promise. Uptake patterns in perianal fistulas, which may be an incidental finding on PET/CT, have not been purposefully studied. Our aim was to compare FDG uptake of perianal fistulas to that of the liver and anal canal in patients who underwent PET/CT for hematologic/oncologic diagnosis or staging. MATERIALS AND METHODS: We retrospectively identified patients who underwent FDG-PET/CT imaging between January 2011 and May 2023, where the report described a perianal fistula or abscess. PET/CTs of patients included in the study were retrospectively analyzed to record the maximum standardized uptake value (SUVmax) of the fistula, abscess, anal canal, rectum, and liver. Fistula-to-liver and Fistula-to-anus SUVmax ratios were calculated. We statistically compared FDG activity among the fistula, liver, and anal canal. We also assessed FDG activity in patients with vs. without anorectal cancer, as well as across different St. James fistula grades. RESULTS: The study included 24 patients with identifiable fistulas. Fistula SUVmax (mean=10.8 ± 5.28) was significantly higher than both the liver (mean=3.09 ± 0.584, p < 0.0001) and the anal canal (mean=5.98 ± 2.63, p = 0.0005). Abscess fistula SUVmax was 15.8 ± 4.91. St. James grade 1 fistulas had significantly lower SUVmax compared to grades 2 and 4 (p = 0.0224 and p = 0.0295, respectively). No significant differences existed in SUVmax ratios between anorectal and non-anorectal cancer groups. CONCLUSION: Perianal fistulas have increased FDG avidity with fistula SUVmax values that are significantly higher than the anal canal.

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

Background: 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. Methods: 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. Results: 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%). Conclusions: Improvements in multidisciplinary CPF care are required to optimize treatment.

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

AIM: 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. METHODS: 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. RESULTS: 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. CONCLUSION: In this real-world experience, treatment of Crohn's disease complex perianal fistulas with darvadstrocel had a 61% success rate for maintained clinical remission.

Surface-enhanced Raman spectroscopy analysis reveals biochemical difference in urine of patients with perianal fistula.

BACKGROUND & AIMS: Perianal fistulising Crohn's disease (PFCD) is different from the characteristics and outcomes of traditional non-inflammatory bowel disease (IBD) anal fistulas. The presence of perianal disease was a poor prognostic indicator for Crohn's disease (CD) patients and PFCD patients were more likely to bear an increased risk of recurrence. However, the effective and accurate diagnosis methods to early distinguish PFCD from simple perianal fistula were still scarce. The purpose of this study is to develop a non-invasive detecting approach to predict CD in patients with perianal fistulas. METHODS: Data on patients with anal fistulizing disease were collected from July 2020 to September 2020 in two IBD centers. Urine samples from PFCD and simple perianal fistula patients were investigated by surface-enhanced Raman spectroscopy (SERS). Principal component analysis (PCA)-support vector machine (SVM) was utilized to establish classification models to distinguish PFCD from simple perianal fistula. RESULTS: After a case-matched 1:1 selection by age and gender, 110 patients were included in the study. By analyzing the average SERS spectra of PFCD and simple perianal fistula patients, it revealed that there were significant differences in intensities at 11 Raman peaks. The established PCA-SVM model distinguished PFCD from simple perianal fistula with a sensitivity of 71.43%, specificity 80.00% and accuracy 75.71% in the leave-one-patient-out cross-validation. The accuracy of the model in validation cohort was 77.5%. CONCLUSIONS: Investigation of urine samples by SERS helps clinicians to predict Crohn's disease from perianal fistulas, which make patients achieve benefit from a more individualized treatment strategy.

Recommendations for Standardizing MRI-based Evaluation of Perianal Fistulizing Disease Activity in Pediatric Crohn's Disease Clinical Trials.

BACKGROUND: Perianal fistulas and abscesses occur commonly as complications of pediatric Crohn's disease (CD). A validated imaging assessment tool for quantification of perianal disease severity and activity is needed to evaluate treatment response. We aimed to identify magnetic resonance imaging (MRI)-based measures of perianal fistulizing disease activity and study design features appropriate for pediatric patients. METHODS: Seventy-nine statements relevant to MRI-based assessment of pediatric perianal fistulizing CD activity and clinical trial design were generated from literature review and expert opinion. Statement appropriateness was rated by a panel (N = 15) of gastroenterologists, radiologists, and surgeons using modified RAND/University of California Los Angeles appropriateness methodology. RESULTS: The modified Van Assche Index (mVAI) and the Magnetic Resonance Novel Index for Fistula Imaging in CD (MAGNIFI-CD) were considered appropriate instruments for use in pediatric perianal fistulizing disease clinical trials. Although there was concern regarding the use of intravascular contrast material in pediatric patients, its use in clinical trials was considered appropriate. A clinically evident fistula tract and radiologic disease defined as at least 1 fistula or abscess on pelvic MRI were considered appropriate trial inclusion criteria. A coprimary clinical and radiologic end point and inclusion of a patient-reported outcome were also considered appropriate. CONCLUSION: Outcomes of treatment of perianal fistulizing disease in children must include MRI. Existing multi-item measures, specifically the mVAI and MAGNIFI-CD, can be adapted and used for children. Further research to assess the operating properties of the indices when used in a pediatric patient population is ongoing.

Temporary Faecal Diversion for Refractory Perianal and/or Distal Colonic Crohn's Disease in the Biologic Era: An Updated Systematic Review with Meta-analysis.

BACKGROUND AND AIMS: We evaluated short- and long-term outcomes of temporary faecal diversion [FD] for management of refractory Crohn's disease [CD], focusing on outcomes in the biologic era. METHODS: Through a systematic literature review until March 15, 2023, we identified 33 studies [19 conducted in the biologic era] that evaluated 1578 patients with perianal and/or distal colonic CD who underwent temporary FD [with intent of restoring bowel continuity] and reported long-term outcomes [primary outcome: successful restoration of bowel continuity, defined as remaining ostomy-free after reconnection at a minimum of 6 months after diversion or at the end of follow-up]. We calculated pooled rates (with 95% confidence interval [CI]) using random effects meta-analysis, and examined factors associated with successful restoration of bowel continuity. RESULTS: Overall, 61% patients [95% CI, 52-68%; 50% in biologic era] experienced clinical improvement after FD. Stoma takedown was attempted in 34% patients [28-41%; 37% in biologic era], 6-18 months after diversion. Among patients where bowel restoration was attempted, 63% patients [54-71%] had successful restoration of bowel continuity, and 26% [20-34%] required re-diversion. Overall, 21% patients [17-27%; 24% in biologic era] who underwent FD were successfully restored; 34% patients [30-39%; 31% in biologic era] required proctectomy with permanent ostomy. On meta-regression, post-diversion biologic use and absence of proctitis was associated with successful bowel restoration after temporary FD in contemporary studies. CONCLUSION: In the biologic era, temporary FD for refractory perianal and/or distal colonic CD improves symptoms in half the patients, and bowel continuity can be successfully restored in a quarter of patients.

Comparison of Contrast-Enhanced 3D Imaging with 2D Imaging in the Evaluation of Perianal Fistula at 3T: A Prospective Observational Study.

Introduction Perianal fistula and its recurrence is a challenging entity for surgeons. It is a well-establi1shed fact that magnetic resonance imaging (MRI) findings influence surgical procedures and reduce the rate of recurrence. In this study, we assessed the contrast-enhanced (CE) three dimensional T1 sequences [sampling perfection with application optimized contrast using different flip angle evolution (SPACE) and volumetric interpolated breath-hold examination (VIBE)] in a 3T MRI system to evaluate perianal fistulas and compared them with two-dimensional (2D) sequences. Materials and Methods Forty-four patients (mean age, 38.8 ± 15.3 [standard deviation]; 32 males, 12 females) with perianal fistula were included in this prospective study. The patients underwent conventional noncontrast, 2D sequences, diffusion-weighted imaging, followed by postcontrast, 2D T1 images in both axial and coronal planes, and 3D sequences at 3T. Acquisition times were recorded for each sequence. Each postcontrast sequence was evaluated in terms of image quality, presence of artifacts, fistula type, presence of an abscess, visibility, and number of internal orifices. The surgical findings were considered the gold standard. The imaging findings were compared with the surgical findings. Results In all three sequences, the fistula type and abscess were identified correctly in all patients. The sensitivity value for identification of ramifications utilizing CE 3D T1 VIBE sequence, CE 3D T1 SPACE, and CE 2D T1 images was 100, 86, and 36%, respectively. The number of internal orifices was identified by the CE 3D T1 VIBE and CE 3D T1 SPACE sequences in 100 and 92% of patients, respectively. CE 2D T1 images correctly identified internal orifices in 80% of patients. The overall scan time for each 3D sequence was shorter than for the combined postcontrast 2D sequences. Conclusion CE 3D T1 SPACE and CE 3D T1 VIBE sequences outperformed conventional CE 2D sequences in the evaluation of perianal fistulas in terms of visibility and the number of internal orifices with a shorter scanning time. Among the 3D sequences, CE 3D T1 VIBE is slightly superior to CE 3D T1 SPACE sequence.