An injection with autologous platelet-rich stroma (PRS), a combination of stromal vascular fraction and platelet-rich plasma, as an add-on to fistula curretage and closure of the internal orifice proved to be safe and feasible for the treatment of patients with treatment-refractory perianal fistulizing Crohn's disease (pCD). This study aimed to assess the long-term outcomes in patients with pCD treated with autologous PRS injection.

Adult patients with therapy-refractory pCD (failure to anti-tumor necrosis factor [TNF] therapy and/or fistula surgery), who underwent fistula curettage, closure of the internal fistula orifice, and autologous PRS injection in a Dutch tertiary referral center were included in an earlier conducted pilot study (n = 25). The primary outcome was complete clinical closure at long-term follow-up (closure of all treated external opening[s]). Secondary outcomes were partial clinical closure (closure of ≥1 treated external opening[s]), radiologic healing (fibrotic fistula tract on magnetic resonance imaging), and recurrence.

The majority of the patients were female (56%) (mean age 34.4 years [standard deviation - SD: 0.9], and mean follow-up 3.7 years [SD: 0.6]). The treatment-refractory character of the study cohort was displayed by the high rate of patients with ≥1 external opening (60%), prior exposure to an anti-TNF agent (92%), TOpClass classification system ≥ class 2b (36%), and the low rate of patients who underwent prior surgical interventions aimed at fistula closure (12%). During long-term follow-up, complete clinical closure was achieved in 88%. Partial clinical closure was achieved in all patients. Radiologic healing was achieved in 75% of the patients. Recurrence was reported in 8% of the patients who achieved prior clinical closure. No recurrences were observed in patients with radiologic healing. Seventeen unplanned re-interventions were reported in nine patients (36%), predominantly for residual fistulizing disease and in patients with severe therapy-refractory pCD (TOpClass classification system ≥ class 2b) at the time of inclusion.

Additional PRS injection, fistula curettage, and closure of the internal orifice is a promising therapy for patients with (treatment-refractory) pCD and could improve clinical and radiologic healing rates. In addition, low recurrence rates were observed. Future randomized research is warranted in order to assess the effectiveness and positioning of PRS in the field of pCD.

NL8417.

Perianal fistulizing Crohn's disease (pfCD) represents a severe manifestation of Crohn's disease (CD) that often leads to significant morbidity. Clinical examination alone of perianal fistulae is unlikely to be sufficient in the context of complex pfCD, as patients are likely to have complex disease and are more likely to experience complications, treatment failure, and recurrent disease. Furthermore, the relapsing-remitting nature of Crohn's disease and our limited understanding of the pathogenesis of this potentially destructive disease necessitate regular examination and radiological assessment, often in the form of magnetic resonance imaging (MRI). Recent advancements in diagnostic techniques have enhanced the accuracy and timeliness of pfCD diagnosis, facilitating better patient outcomes. A growing appreciation of isolated perianal Crohn's disease has prompted a recent attempt to develop consensus recommendations on diagnosing and treating this group of patients who would previously not have been offered CD medications. This narrative review aims to summarize current practice and the latest developments in the diagnosis of pfCD, highlighting: 1. Clinical examination and assessment tools 2. Current imaging practices 3. Innovations in imaging and biomarkers 4. The diagnosis of isolated perianal Crohn's disease.

Perianal fistulising Crohn's disease (pfCD) affects one-fifth of patients with Crohn's disease (CD), significantly affecting their quality of life. Magnetic resonance imaging is the gold standard for evaluating fistula healing in pfCD, but variability in radiological definitions hampers meaningful clinical interpretation and consistent trial design. This study aimed to establish an international consensus on the definition of radiological healing in pfCD.

The study was conducted in 2 phases. Phase 1 involved a systematic review to identify magnetic resonance imaging-based variables and indices used to define healing in pfCD, assessing methodological quality using the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) framework. Phase 2 utilized a 2-round online Delphi consensus process with 84 international experts, followed by a stakeholder meeting to achieve consensus (agreement threshold >80%). Results were reported as per Accurate Consensus Reporting Document (ACCORD) guidelines.

A radiologically healed fistula can be defined by the absence of T2-weighted hyperintensity, a completely fibrotic fistula tract and, when contrast is used, the absence of contrast enhancement on post-contrast T1-weighted images (95% consensus). Radiological improvement of a fistula can be defined (80% consensus) by the presence of a least one essential criterion: an increasingly fibrotic fistula tract, an unequivocal reduction in one or more of the following: T2-weighted hyperintensity, fistula diameter, fistula length, abscess size, or contrast enhancement of the fistula tract.

This international Delphi consensus standardizes radiological endpoints in pfCD, improving consistency in clinical and research settings. Future studies will validate this definition and assess how radiological changes predict long-term clinical outcomes and quality of life improvements.

Previous literature suggests that faecal calprotectin (FC) discriminates Crohn's disease perianal fistulas from cryptoglandular fistulas, irrespective of luminal disease. This study aims to prospectively validate this and analyse if increased local fistula calprotectin levels are associated with fistula characteristics.

In this prospective study, all consecutive patients with an active perianal fistula undergoing examination under anaesthesia were included. Faecal and fistula tract scraping calprotectin levels were determined. The primary objective was to analyse whether FC levels could be used to differentiate between Crohn's disease and cryptoglandular perianal fistulas. Secondary outcome parameters were the levels of local calprotectin in fistula scrapings and their correlation with fistula characteristics.

Sixty-three patients were included in this study (perianal Crohn's disease; 45, cryptoglandular; 18). Faecal calprotectin levels were significantly higher in Crohn's disease patients compared with cryptoglandular fistula (354.3 [58.8-1076.3] vs. 47.3 [14.6-233.6] μg/g, p = 0.003). Faecal calprotectin could accurately discriminate Crohn's disease patients with active luminal disease from patients without luminal disease (median [interquartile range]) (1167.0 [557.0-2806.3] vs. 93.0 [47.5-571.6] μg/g, p = 0.001). Faecal calprotectin was not related to calprotectin levels in fistula scrapings. No fistula characteristic was found to be correlated to scraping calprotectin, but a correlation was found with the TOpCLASS classification system, which stratifies fistulas according to disease severity and outcome: class 2a (amenable for repair), class 2b (symptom control) and class 2c (gradually debilitating disease): 140[31.0-149.0]) μg/g versus 706[198.5-1936] μg/g versus 4000[1337-5894] μg/g, p < 0.001). Scraping calprotectin was also related to pronounced hyperintensity of the fistula tract on MRI in Crohn's disease patients: (69.0[30.0-821.0] vs. 1284.0[204.3-4185.5]; p = 0.01)) and cryptoglandular patients: (30.0[13.5-80.5] vs. 3012.0 [923.8-5021.0]; p = 0.002).

Crohn's disease and cryptoglandular perianal fistulas differ in FC levels. Local fistula calprotectin production did not explain this difference, implying FC reflects the luminal condition. A correlation exists between scraping calprotectin levels and Crohn's disease fistula severity, which could be clinically relevant for prognostic cohorts and tailored treatment.

We aimed to assess inter-radiologist agreement when interpreting pelvic MRI in children with newly diagnosed perianal Crohn's disease (CD).

In this retrospective multi-reader study, we identified pediatric patients (< 18 years of age) who underwent a pelvic MRI examination for newly diagnosed perianal CD. Images were de-identified and uploaded to a cloud-based image platform for review by 13 fellowship-trained pediatric radiologists The reviewers assessed for the presence of a fistula and abscess, categorization of different imaging findings, and classification using the Parks and St James' University Hospital systems. Fleiss' kappa (κ) statistics and intra-class correlation coefficients (ICC) were used to measure inter-reader agreement, along with 95% confidence intervals (CI).

Forty-six patients were included in our study (median age = 13.0 years [IQR: 10.5 to 16.0 years]); thirty-five (76.1%) were boys. Most imaging features showed fair agreement (κ = 0.21 to 0.35). There was moderate agreement for categorical fistula length (κ = 0.42 [95% CI: 0.32 to 0.53]), involvement of the genitalia (κ = 0.45 [95% CI: 0.26 to 0.63]), and presence of an abscess/collection (κ = 0.52 [95% CI: 0.31 to 0.73]). Maximum abscess/collection length had good agreement (ICC = 0.81 [95% CI: 0.41, 1.00]). There was an almost equal split (yes vs. no: 50.7% vs. 49.3%) regarding whether postcontrast T1-weighted images added value compared to T2-weighted images alone across all radiologists and examinations.

Inter-radiologist agreement when interpreting pelvic MRI for perianal CD in children is fair for most imaging features, with fewer features demonstrating moderate or good agreement.

Question Pelvic magnetic resonance imaging (MRI) is used for diagnosing and monitoring children with perianal Crohn's disease (CD). Limited information is known about inter-radiologist agreement. Findings Agreement between pediatric radiologists when interpreting MRI for perianal CD in children is only fair for most imaging features (κ = 0.21 to 0.35). Clinical relevance Understanding MRI inter-radiologist agreement is crucial to improve the reliability of pelvic MRI in children with perianal Crohn's disease since it may affect patient management (e.g., surgery); further radiologist education and improved imaging feature definitions may help improve inter-radiologist agreement.

There is an increasing need for objective treatment monitoring in perianal fistulising Crohn's disease (pfCD). Therefore, the magnetic resonance novel index for fistula imaging in CD (MAGNIFI-CD) index has been designed and internally validated on the ADMIRE-CD trial cohort. The aim of this study was to externally validate the MAGNIFI-CD index to monitor response to medical and surgical treatment regimens in pfCD.

A retrospective longitudinal cohort was established of consecutive patients with complex pfCD treated with surgical and/or medical therapy and a baseline and follow-up MRI between January 2007 and May 2021. The MAGNIFI-CD index was scored by two independent, abdominal radiologists blinded for time points and clinical outcomes. Responsiveness, reliability, and test accuracy regarding clinically important improvement were assessed. Cut-offs for response and remission were selected classified on fistula drainage assessment and physician global assessment.

A total of 65 patients (51% female, median age 32 years) were included. A clinically relevant responsiveness of the MAGNIFI-CD was shown, with a significant decrease in clinical remitters and responders with a median MAGNIFI-CD of 18.0 [7.5-20.0] to 9.0 [0.8-16.0] (p < 0.001) and non-significant change in non-responders with a median MAGNIFI-CD of 20.0 [12.0-23.0] to 18.0 [13.0-21.0] (p = 0.22). There was an 'almost perfect' interobserver agreement (ICC = 0.87; 95% CI 0.80-0.92) for the MAGNIFI-CD index. An optimal cut-off value was defined as a decrease of 2 points for clinical response, and a MAGNIFI-CD ≤ 6 for remission at follow-up MRI.

The MAGNIFI-CD index is a responsive and reliable MRI scoring instrument for treatment monitoring in perianal fistulising Crohn's disease.

The MAGNIFI-CD index is a well-structured, responsive scoring instrument to assess fistula severity and activity that allows quantitative detection of changes in therapy response in patients with perianal fistulising Crohn's disease, thereby facilitating endpoints in clinical trials.

Well-defined cut-offs for response and remission are needed for objective treatment monitoring of perianal fistulising Crohn's disease (pfCD). Cut-off values for remission and for response at 6 months follow-up were defined. Interobserver agreement was good. The MAGNIFI-CD index is responsive and reliable for treatment monitoring and is suitable for use in clinical trials.

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

Crohn's perianal fistula healing rates remain low. We evaluated the efficacy of a protocolized multidisciplinary treatment strategy optimizing care in adults with Crohn's perianal fistulas.

A new treatment strategy was established at a single tertiary center. The strategy comprised 3 dynamic stages of care directed toward achieving and maintaining fistula healing. Stage A, active disease, focused on early commencement and proactive escalation of biologic therapies and structured surgical reviews ensuring adequate fistula drainage and conditioning. Stage B, optimized disease with a seton in situ, focused on consideration for seton removal and appropriateness of definitive surgical closure and/or ablative techniques. Stage C, healed disease, focused on proactive care maintenance. Sixty patients were sequentially enrolled and prospectively followed for ≥12 months. Endpoints included clinical healing and radiologic remission in those with clinically active fistulas, and relapse in those with healed fistulas.

At baseline, 52% (n = 31) and 48% (n = 29) had clinically active and healed fistulas, respectively. For patients with clinically active fistulas, 71% achieved clinical healing after 22 months, with estimated healing rates of 39% and 84% at 1 and 2 years, respectively. Radiologic remission was achieved in 25%, significantly higher than baseline inclusion rates of 6%. For patients with healed fistulas, 7% experienced clinical relapse after 23 months, with no significant change in radiologic remission, 80% versus 86% at baseline.

A protocolized treatment strategy proactively optimizing care resulted in high rates of clinical healing and improved radiologic remission of Crohn's perianal fistulas. Controlled-matched studies are needed.

Perianal fistulising Crohn's disease (pfCD) is a distinct and debilitating phenotype seen in around one-third of patients with CD. Clinical trials in pfCD are increasingly using magnetic resonance imaging (MRI) criteria as a primary endpoint, but there is heterogeneity in the radiological definition of a healed perianal fistula that currently limits our ability to perform meaningful meta-analyses of studies. Our aim is to standardise outcomes through the generation of an international consensus definition of a radiologically healed fistula.

This international Delphi consensus study employs a two-part strategy.The first is a systematic review to identify a longlist of variables used to define radiological healing in pfCD. MRI-based indices used to score fistula severity and healing will be assessed for their methodological quality using Consensus-based Standards for the selection of health Measurement Instruments (COSMIN). The systematic review protocol will be conducted using COSMIN methodology and reported using Preferred Reporting Items for Systematic Reviews and Meta-Analyses.The second part will be an online Delphi consensus, guided by the results of the systematic review. Radiologists, gastroenterologists and colorectal surgeons with expertise in the management of pfCD will be invited to take part in two to three rounds of online surveys. Once an a priori threshold of >80% agreement is reached on individual radiological components used to define 'healing' and 'healed', a final meeting of key stakeholders will be organised to generate a consensus definition of a healed fistula.

The study has been deemed exempt from a formal Research Ethics Committee review as no patients will participate directly in the consensus process, given the technical nature of the research question. The study is registered with the local R&D department (Reference RD24/007). Publication of this study will help standardise radiological endpoint measurement in clinical trials of pfCD and improve the synthesis and meta-analysis of comparative studies.

CRD42024504334.

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.

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.

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.

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.

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 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.

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.

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).

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.

Perianal fistulas pose dual challenges to Crohn's disease (CD) patients. Low patient compliance due to the complexity of existing examination methods plagues the treatment and follow-up management of perianal CD.

To determine the accuracy of endoanal ultrasound (EUS) and shear wave elastography (SWE) for evaluating perianal fistulizing CD (PFCD) activity.

This was a retrospective cohort study. A total of 67 patients from August 2022 to December 2023 diagnosed with CD were divided into three groups: Non-anal fistula group (n = 23), low-activity perianal fistulas [n = 19, perianal disease activity index (PDAI) ≤ 4], high-activity perianal fistulas (n = 25, PDAI > 4) based on the PDAI. All patients underwent assessments including EUS + SWE, pelvic magnetic resonance [pelvic magnetic resonance imaging (MRI)], C-reactive protein, fecal calprotectin, CD activity index, PDAI.

The percentage of fistulas indicated by pelvic MRI and EUS was consistent at 82%, and there was good consistency in the classification of perianal fistulas (Kappa = 0.752, P < 0.001). Significant differences were observed in the blood flow Limberg score (χ 2 = 8.903, P < 0.05) and shear wave velocity (t = 2.467, P < 0.05) between group 2 and 3. Shear wave velocity showed a strong negative correlation with magnetic resonance novel index for fistula imaging in CD (Magnifi-CD) score (r = -0.676, P < 0.001), a weak negative correlation with the PDAI score (r = -0.386, P < 0.05), and a weak correlation between the Limberg score and the PDAI score (r = 0.368, P < 0.05).

EUS combined with SWE offers a superior method for detecting and quantitating the activity of perianal fistulas in CD patients. It may be the ideal tool to assess PFCD activity objectively for management strategies.

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.

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.

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).

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.

Mesenchymal stem cell treatment (MST) has emerged as a new therapeutic strategy for Crohn's perianal fistulas. It has been demonstrated that a fibrotic tract on MRI with a MAGNIFI-CD score ≤ 6 is the best predictor for long-term clinical closure. Therefore, the aim of the current study was to analyse the effectiveness of MST for complex Crohn's perianal fistulas based on MRI.

Consecutive patients with complex Crohn's perianal fistulas, previously failing both anti-TNF treatment and surgical closure, who had surgical closure of the internal opening with MST were included. The primary endpoint was radiological remission of the fistula(s) defined as a MAGNIFI-CD ≤ 6 on MRI, read by an experienced radiologist.

Between December 2019 and March 2023, 30 patients (15 males) with 48 fistula tracts were included with a median follow-up of 16.5 months. Radiological remission was achieved in thirteen patients (43.3%) after a median follow-up of 5.0 months (IQR 3.0-6.0). The median MAGNIFI-CD at baseline was 15.0 (IQR 7.0-20.0) which significantly decreased to 8.0 (IQR 3.0-15.0) after treatment (p = 0.001). Clinical closure was achieved in 21 patients (70.0%). Three patients (14.3%) developed a recurrence during long-term FU, all with clinically closed fistula(s), but no radiological remission. The median PDAI decreased significantly from 10.5 (IQR 7.0-14.0) to 4.0 (IQR 0.0-7.3) (p = 0.001).

MST is a promising treatment strategy for therapy refractory Crohn's perianal fistulas, resulting in > 40% radiological remission, clinical closure in 70% and a significant improvement in quality of life. No recurrences were seen in patients with radiological remission.

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.

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.

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.

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 ligation of intersphincteric fistula tract is a surgical technique designed to treat trans-sphincteric anal fistulas aiming to preserve sphincter integrity. Recent studies suggest its efficacy in short-term fistula healing with limited impact on continence. However, comprehensive prospective data on long-term outcomes, including recurrence and bowel continence, are limited. The present study aims to report on the long-term functional outcomes.

Patients who underwent the ligation of intersphincteric fistula tract procedure for trans-sphincteric cryptoglandular anal fistulas between July 2012 and October 2018 at two Dutch referral centres were retrospectively reviewed. The primary outcome of interest was the long-term bowel continence after the ligation of intersphincteric fistula tract procedure, using the faecal incontinence severity index. Short-term data (collected in 2018) and long-term data (collected in 2023) on bowel continence, healing rates and recurrences were obtained through electronic records and Rockwood questionnaires. Sankey diagrams were used to visually represent individual variations in continence status (preoperative versus follow-up).

Among 110 patients included (50% female, median follow-up 92 months), 101 patients (92%) were treated with previous surgeries (median 2, range 0-6) and 80% had previous seton drainage. Preligation of intersphincteric fistula tract, 16% of the patients reported incontinence (mean(s.d.) faecal incontinence severity index: 2.4(7.5), increasing to 18% after ligation of intersphincteric fistula tract at short-term follow-up, including 11% newly induced cases. Long-term follow-up collected using Rockwood questionnaires (63% response rate) in 69 patients uncovered a 74% incontinency rate (mean(s.d.) faecal incontinence severity index: 9.22(9.5). In those patients without subsequent surgery 49% (17 of 35) reported incontinence at long-term follow-up. Primary fistula healing after ligation of intersphincteric fistula tract was 28%. Preoperative seton drainage significantly improved healing rates (33% versus 9%). Notably, 43% (34 of 79) of unhealed fistulas transitioned into intersphincteric tracts; in these patients, 19 were treated with subsequent fistulotomy achieving cure in 18 cases.

Ligation of intersphincteric fistula tract healing rates fell below recent literature standards. Although the immediate impact on postoperative continence appears minimal, long-term incontinence rates are concerning. In recognizing the deterioration of individual continence, we advocate for a patient-centered approach and urge fellow researchers and clinicians to collect comprehensive prospective continence data.

Clinical and radiologic variables associated with perianal fistula (PAF) outcomes are poorly understood. We developed prediction models for anti-tumor necrosis factor (TNF) treatment failure in patients with Crohn's disease-related PAF.

In a multicenter retrospective study between 2005 and 2022 we included biologic-naive adults (>17 years) who initiated their first anti-TNF therapy for PAF after pelvic magnetic resonance imaging (MRI). Pretreatment MRI studies were prospectively reread centrally by blinded radiologists. We developed and internally validated a prediction model based on clinical and radiologic parameters to predict the likelihood of anti-TNF treatment failure, clinically, at 6 months. We compared our model and a simplified version of MRI parameters alone with existing imaging-based PAF activity indices (MAGNIFI-CD and modified Van Assche MRI scores) by De Long statistical test.

We included 221 patients: 32 ± 14 years, 60% males, 76% complex fistulas; 68% treated with infliximab and 32% treated with adalimumab. Treatment failure occurred in 102 (46%) patients. Our prediction model included age at PAF diagnosis, time to initiate anti-TNF treatment, and smoking and 8 MRI characteristics (supra/extrasphincteric anatomy, fistula length >4.3 cm, primary tracts >1, secondary tracts >1, external openings >1, tract hyperintensity on T1-weighted imaging, horseshoe anatomy, and collections >1.3 cm). Our full and simplified MRI models had fair discriminatory capacity for anti-TNF treatment failure (concordance statistic, 0.67 and 0.65, respectively) and outperformed MAGNIFI-CD (P = .002 and < .0005) and modified Van Assche MRI scores (P < .0001 and < .0001), respectively.

Our risk prediction models consisting of clinical and/or radiologic variables accurately predict treatment failure in patients with PAF.

Perianal fistulizing Crohn's disease (CD-PAF) is an aggressive phenotype of Crohn's disease (CD) defined by frequent relapses and disabling symptoms. A novel consensus classification system was recently outlined by Geldof et al. 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.

We identified all patients with CD-PAF and at least one baseline and one follow-up pelvic (pMRI). Geldof Classification, disease characteristics, and imaging indices were collected retrospectively at time periods corresponding with respective MRIs.

We identified 100 patients with CD-PAF of which 96 were assigned Geldof 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. 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.

Geldof classification highlights the dynamic nature of CD-PAF 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 Geldof classification.

The injection of allogeneic adipose tissue-derived mesenchymal stem cells (MSC) into anal fistulas in patients with Crohn's disease has never been evaluated in "real-life" conditions in France.

We prospectively studied the first patients receiving MSC injections at our center and undergoing 12 months of follow-up. The primary endpoint was the clinical and radiological response rate. The secondary endpoints were symptomatic efficacy, safety, anal continence, quality of life (Crohn's anal fistula-quality of life scale, CAF-QoL), and predictive factors of success.

We included 27 consecutive patients. The complete clinical and radiological response rates at M12 were 51.9% and 50%, respectively. The combined complete clinical-radiological response (deep remission) rate was 34.6%. No major adverse effects or changes in anal continence were reported. The perianal disease activity index decreased from 6.4 to 1.6 (p < 0.001) for all patients. The CAF-QoL score also decreased from 54.0 to 25.5 (p < 0.001). At the end of the study, M12, the CAF-QoL score was significantly lower only in patients with a complete combined clinical-radiological response relative to those without a complete clinical-radiological response (15.0 versus 32.8, p = 0.01). Having a multibranching fistula and infliximab treatment were associated with a combined complete clinical-radiological response.

This study confirms reported efficacy data for the injection of MSC for complex anal fistulas in Crohn's disease. It also shows a positive impact on the quality of life of patients, particularly those for whom a combined clinical-radiological response was achieved.

This review focuses on the role of magnetic resonance imaging (MRI) in the evaluation of the gastrointestinal tract (GI MRI), analyzing the major technical advances achieved in this field, such as diffusion-weighted imaging, molecular imaging, motility studies, and artificial intelligence. Today, MRI performed with the more advanced imaging techniques allows accurate assessment of many bowel diseases, particularly inflammatory bowel disease and rectal cancer; in most of these diseases, MRI is invaluable for diagnosis, staging, and disease monitoring under treatment. Several MRI parameters are currently considered activity biomarkers for inflammation and neoplastic disease. Furthermore, in younger patients with acute or chronic GI disease, MRI can be safely used for short-term follow-up studies in many critical clinical situations because it is radiation-free. MRI assessment of functional gastro-esophageal and small bowel disorders is still in its infancy but very promising, while it is well established and widely used for dynamic assessment of anorectal and pelvic floor dysfunction; MRI motility biomarkers have also been described. There are still some limitations to GI MRI related to high cost and limited accessibility. However, technical advances are expected, such as faster sequences, more specific intestinal contrast agents, AI analysis of MRI data, and possibly increased accessibility to GI MRI studies. Clinical interest in the evaluation of bowel disease using MRI is already very high, but is expected to increase significantly in the coming years.

The PISA-II trial showed that short-term anti-tumour necrosis factor (anti-TNF) therapy followed by surgical closure induces radiological healing of perianal fistulas in patients with Crohn's disease more frequently than anti-TNF therapy alone after 18 months. This study aimed to compare long-term outcomes of both treatment arms.

Follow-up data were collected from patients who participated in the PISA-II trial, an international patient preference randomised controlled trial. This multicentre trial was performed in nine hospitals in the Netherlands and one hospital in Italy. Patients with Crohn's disease above the age of 18 years with an active high perianal fistula and a single internal opening were asked to participate. Patients were allocated to anti-TNF therapy (intravenous infliximab, or subcutaneous adalimumab, at the discretion of the gastroenterologist) for one year, or surgical closure combined with 4-months anti-TNF therapy. Patients without a treatment preference were randomised (1:1) using random block randomisation (block sizes of six without stratification), and patients with a treatment preference were treated according to their preferred treatment arm. For the current follow-up study, data were collected until May 2022. Primary outcome was radiological healing on magnetic resonance imaging (MRI), including all participants with a MRI made less than 6 months ago at the time of data collection. Analysis was based on observed data.

Between September 14, 2013, and December 7, 2019, 94 patients were enrolled in the trial. Long-term follow-up data were available in 91 patients (36/38 (95%) anti-TNF + surgical closure, 55/56 (98%) anti-TNF). A total of 14/36 (39%) patients in the surgical closure arm were randomly assigned, which was not significantly different in the anti-TNF treatment arm (16/55 (29%) randomly assigned). Median follow-up was 5.7 years (interquartile range (IQR) 5-7). Radiological healing occurred significantly more often after anti-TNF + surgical closure (15/36 = 42% versus 10/55 = 18%; P = 0.014). Clinical closure was comparable (26/36 = 72% versus 34/55 = 62%; P = 0.18) in both groups. However, clinical closure in the surgical group was achieved with less re-interventions 4/26 (= 15%) versus 18/34 (= 53%), including (redo-)surgical closure procedures. Recurrences occurred in 0/25 (0%) patients with radiological healing versus 27/76 (36%) patients with clinical closure, sometime during follow-up. Anti-TNF trough levels were higher in patients with long-term clinical closure in both groups (P = 0.031 and P = 0.014). In 6/11 (55%) patients in the anti-TNF group with available trough levels, recurrences were diagnosed within three months of a drop under 3.5ug/ml. 36 patients stopped anti-TNF, after which 0/14 (0%) patients with radiological healing developed a recurrence and 9/22 (41%) with clinical closure. Self-rated (in)continence was comparable between groups, and 79% (60/76) of patients indicated comparable/improved continence after treatment. Decision-regret analysis showed that all (30/30) anti-TNF + surgical closure patients agreed or strongly agreed that surgery was the right decision versus 78% (36/46) in the anti-TNF arm. All surgical closure patients would go for the same treatment again, whereas this was 89% (41/46) in the anti-TNF arm.

This study confirmed that surgical closure should be considered in amenable patients with perianal fistulas and Crohn's disease as long-term outcomes were favourable, and that radiological healing should be the aim of treatment as recurrences only occurred in patients without radiological healing. In patients with complete MRI closure, anti-TNF could be safely stopped.

None.

Despite progress in multidisciplinary diagnostic and therapeutic strategies, complex anal fistulas associated with Crohn's disease remain a challenge for both medical and surgical management. Conventional surgical techniques such as flap procedures or LIFT are still associated with considerable persistence and recurrence rates. Based on this background, results of stem cell therapy for Crohn's anal fistula have shown promising results and are a sphincter-preserving technique. In particular, adipose-derived, allogeneic stem cell therapy (Darvadstrocel) has shown encouraging healing rates within the randomised controlled ADMIRE-CD trial, which were reproducible in "real world" data of limited clinical studies. The current evidence has led to the integration of allogeneic stem cell therapy into international guidelines. To date, the definitive status of allogeneic stem cells in the multidisciplinary treatment algorithm for complex anal fistulas associated with Crohn's disease cannot be evaluated.

Cross-sectional magnetic resonance enterography (MRE) and intestinal ultrasonography (IUS) provide valuable and noninvasive information to accurately assess disease activity, severity, and extent; detect complications; and monitor the response to treatment, as well as predict the postoperative recurrence of Crohn's disease and a negative disease course. Therefore, both imaging modalities are emerging as pivotal diagnostic tools to achieve the emerging therapeutic target of transmural healing associated with better disease outcomes. Despite its numerous potential advantages over endoscopy and even MRE and its good availability, IUS is still widely underused to monitor and manage inflammatory bowel disease (IBD) patients and help in making clinical decisions in routine practice. This situation is clearly due to the absence of validated, reliable, and responsive indices, as well as the lack of trained gastroenterologists and radiologists, as IUS is a component of radiologist expertise in several countries but not yet integrated into the training program of gastroenterologists. However, there is an increasing body of evidence in the literature that IUS and MRE are both becoming essential imaging resources to help clinicians in making reliable decisions. Here, we discuss the up-to-date evidence about the usefulness and performance of cross-sectional imaging, focusing on the ability of bowel US and MRE to aid clinical decision-making for the optimal management and monitoring of IBD.