Search Results (117)

Perianal fistulizing Crohn’s disease (pfCD) represents one of the most challenging manifestations of CD, often associated with severe phenotypes, refractory luminal inflammation, and a substantial reduction in quality of life. Its pathogenesis is multifactorial and incompletely understood, involving genetic susceptibility, epithelial and stromal dysfunction, and microbiome-related mechanisms. Diagnosis and monitoring rely on advanced imaging, while management requires coordinated medical–surgical strategies. Significant unmet needs persist regarding standardized treatment targets, optimal imaging follow-up, and personalized therapeutic pathways. In this review, we aim to summarise and provide a comprehensive overview of the most recent evidence across pathogenesis, diagnosis, classification systems, and therapeutic approaches in pfCD. We highlight key advances in understanding epithelial–mesenchymal transition, immune–microbiome interactions, and genetic determinants of disease behaviour. Improvements in diagnostic modalities—including MRI-based scores, ultrasound technologies, volumetric assessment, and AI-enhanced imaging—are discussed alongside modern classification systems such as TOPClass. Evidence guiding medical therapy, seton management, and surgical decision-making is reviewed, emphasising integrated, goal-oriented care. Despite substantial progress, pfCD remains a difficult-to-treat condition with persistent gaps in early diagnosis, objective monitoring, and individualized management. Emerging imaging technologies, standardized treatment targets, and structured classification frameworks offer promising strategies to overcome current limitations and improve long-term outcomes. Full article

Postoperative recurrence (POR) remains a significant challenge in Crohn’s disease (CD) management despite therapeutic advances. Contemporary data show ileocecal resection rates of 18.7%, 28.0%, and 39.5% at one, five, and ten years after diagnosis, with endoscopic recurrence occurring in 22.4–53% of patients within 18–36 months postoperatively. Current understanding of POR pathophysiology includes microbiota dysbiosis, mesenteric inflammation, immune dysregulation, and genetic factors, particularly NOD2 variants. Key risk factors comprehend smoking, penetrating or perianal disease, prior surgeries, and extensive small bowel involvement. The Rutgeerts score remains the endoscopic gold standard for assessing recurrence, though it has never been validated and modifications addressing modern anastomotic techniques have been proposed. Non-invasive monitoring strategies using fecal calprotectin, intestinal ultrasound, and magnetic resonance enterography demonstrate promising diagnostic performance and may reduce the burden of routine endoscopy. Anti-TNF agents and Vedolizumab show superior efficacy in preventing endoscopic recurrence compared to conventional therapies, while other advanced therapies like anti-JAKs, risankizumab and ustekinumab demonstrate potential benefit in postoperative prophylaxis. Management approaches have evolved toward risk-stratified strategies balancing systematic prophylaxis against endoscopy-driven therapy. While medical prophylaxis remains first-line for high-risk patients, the expanding therapeutic armamentarium and improved understanding of pathophysiologic mechanisms enable increasingly personalized postoperative care. Further research is needed to validate risk assessment tools, optimize timing and selection of prophylactic therapies, and define the role of emerging agents in reducing long-term disease burden. Full article

Background/Objectives: Large Language Models (LLMs) may help translate complex Magnetic Resonance Imaging (MRI) fistula reports into accessible, patient-friendly summaries. This study evaluated the clinical utility, safety, and patient acceptability of Generative Pre-trained Transformer (GPT-4o) in generating such reports. Methods: A three-phase study was conducted at a single centre. Phase I involved prompt engineering and pilot testing of GPT-4o outputs for feasibility. Phase II assessed 250 consecutive MRI fistula reports from September 2024 to November 2024, each reviewed by a multi-disciplinary panel to determine hallucinations and thematic content. Phase III randomised patients to review either a simple or complex fistula case, each containing an original report and an Artificial Intelligence (AI)-generated summary (order randomised, origin blinded), and rate readability, trustworthiness, usefulness and comprehension. Results: Sixteen patients participated in Phase I pilot testing. In Phase II, hallucinations occurred in 11% of outputs, with unverified recommendations also identified. In Phase III, 61 patients (mean age 48, 41% female) evaluated paired original and AI-generated summaries. AI summaries scored significantly higher for readability, comprehension, and usefulness than original reports (all p < 0.001), with equivalent trust ratings. Mean Flesch-Kincaid scores were markedly higher for AI-generated summaries (66 vs. 26; p < 0.001). Clinicians highlighted improved anatomical structuring and accessible language, but emphasised risks of inaccuracies. A revised template incorporating Multi-Disciplinary Team (MDT)-focused action points and a lay summary section was co-developed. Conclusions: LLMs can enhance the readability and patient understanding of complex MRI reports but remain limited by hallucinations and inconsistent terminology. Safe implementation requires structured oversight, domain-specific refinement, and clinician validation. Future development should prioritise standardised reporting templates incorporating clinician-approved lay summaries. Full article

Background: Filgotinib is an emerging Janus kinase 1 (JAK1) inhibitor being investigated for inflammatory bowel disease. This systematic review and network meta-analysis (NMA) evaluated the efficacy and safety of filgotinib in adult patients with moderate-to-severe crohn’s disease. Methods: We systematically searched PubMed, EMBASE, and Scopus through April 2025. Randomized controlled trials evaluating filgotinib versus placebo in adults with moderate-to-severe Crohn’s disease were included. Primary outcomes were clinical remission and endoscopic response. Study quality was assessed using the Cochrane Risk of Bias 2.0 tool. A network meta-analysis was performed to integrate direct and indirect evidence, reporting risk ratios (RRs) with 95% confidence intervals (CIs). Results: Five randomized controlled trials (from 4 publications) met the inclusion criteria. Filgotinib 200 mg significantly improved clinical remission compared with placebo (RR: 1.75 [1.40–2.19]) and 100 mg (RR: 1.38 [1.11–1.71]), while 100 mg showed no significant difference versus placebo (RR: 1.27 [0.99–1.63]). For endoscopic response, both 200 mg (RR: 1.72 [1.09–2.69]) and 100 mg (RR: 1.65 [1.02–2.69]) demonstrated significant benefit over placebo, though no difference was observed between active doses (RR: 1.04 [0.64–1.68]; I² = 57%). In the two-item patient-reported outcome, 200 mg showed significant improvement versus placebo (RR: 1.47 [1.20–1.80]) and 100 mg (RR: 1.26 [1.02–1.55]), while 100 mg remained insignificant versus placebo (RR: 1.17 [0.93–1.46]). Neither dose increased the risk of treatment-emergent adverse events, serious adverse events, or infections compared with placebo, with consistent homogeneity across analyses. Conclusions: Filgotinib 200 mg demonstrated superior efficacy across clinical, endoscopic, and patient-reported outcomes compared with 100 mg and placebo, with a favorable safety profile. The 100 mg dose showed limited efficacy and no advantage over placebo. Filgotinib represents a promising oral therapeutic option, particularly for biologic-naïve patients and in maintenance therapy, while also showing potential benefit in perianal fistulising crohn’s disease. Future trials should explore long-term safety and head-to-head comparisons with established biologics. Full article

Background: Perianal involvement is a well-recognized manifestation of Crohn’s disease (CD). However, non-fistulizing perianal phenotypes remain underrecognized despite their significance in clinical practice and impact on patients’ quality of life. Methods: A narrative review of the literature up to September 2025 was conducted, with an emphasis on studies that differentiated between non-fistulizing and fistulizing lesions. Results: During the CD course, approximately 45% of patients with CD develop non-fistulizing perianal manifestations, including fissures, ulcers, strictures, and skin tags. These lesions may resolve spontaneously with the ongoing CD therapy or additional conservative measures, but some evolve into more complex conditions, with challenging management. Deep ulcers and strictures appear to be associated with a less favorable disease course. While biologic therapy has altered the overall course of CD, its role in treating non-fistulizing perianal Crohn’s disease (PCD) requires further understanding. Surgical intervention, which carries an increased risk of complications, is typically reserved for individuals who are refractory to other treatments. The potential association between non-fistulizing PCD and anal cancer remains uncertain. Conclusions: Non-fistulizing PCD is a clinically significant condition that requires early recognition and individualized management. Prospective studies with standardized lesion classification, careful monitoring of disease course, and evaluation of biologic therapies and biomarkers are needed to develop evidence-based strategies and improve patient outcomes on non-fistulizing PCD. Full article

Extramammary Paget’s disease is a rare malignant tumor that frequently presents in areas rich in apocrine glands, most often affecting the skin of the perianal area: the labia minora, clitoris, scrotum, penis, skin of the lower abdomen, and inguinal folds. Tumors localized outside the perianal region are relatively rare. We present a clinical case of a 70-year-old patient with a tumor localized on the skin of the right axillary region, with clinical, histological, and immunohistochemical characteristics. The diagnosis of extramammary Paget’s disease with atypical localization is relatively difficult to reach in time, as tumors are often mistakenly considered as inflammatory skin lesions, and the appropriate treatment may therefore be delayed. Full article

Background: The development of anti-drug antibodies (ADAs) and resulting immune complexes are key mechanisms behind the secondary loss of response to adalimumab in Crohn’s disease (CD). Despite their clinical importance, routine immunogenicity assays are limited, underscoring the need for alternative predictive approaches. Objective: This study aimed to develop interpretable artificial neural network (ANN) models to predict immune complex formation and estimate serum adalimumab levels using routinely available clinical and laboratory data from CD patients. Methods: A prospective analysis was performed on 58 CD patients on maintenance adalimumab. Immune complexes and serum adalimumab were measured via ELISA and lateral flow assays. ANN and ensemble regression models were trained on demographic, clinical, and inflammatory data, with performance evaluated by five-fold cross-validation. Interpretability was enhanced using Garson’s algorithm and permutation importance. Results: The ANN-based classification model accurately predicted ADA immune complex formation, achieving an accuracy of 77.47% and an area under the curve (AUC) of 82.63%. The main predictive variables included extraintestinal manifestations, perianal disease, disease behavior, and age at diagnosis. For estimating serum adalimumab levels measured by ELISA, the model performed modestly (accuracy 59.89%, AUC 79.72%), incorporating factors such as Montreal classification, perianal disease, C-reactive protein, immunosuppressant use, and disease duration. Conclusions: Interpretable ANN models robustly predict anti-adalimumab immune complexes and, to a lesser extent, serum adalimumab, using clinically available data, including perianal disease. This proof-of-concept study is limited by the relatively small, single-center dataset (n = 58), which may affect model generalizability and increase the risk of overfitting. External validation in larger and multicenter cohorts is required before clinical implementation. Full article

Background and Objectives: Postoperative enterocutaneous fistulas, defined as abnormal communications between the intestinal lumen and the skin, represent one of the most challenging complications following abdominal surgery. Regenerative medicine, particularly through the use of adipose-derived mesenchymal stem cells (ADSCs), has recently emerged as a promising therapeutic option for chronic inflammatory and non-healing conditions. However, most studies have focused on complex perianal fistulas in Crohn’s disease. This prospective, single-center observational study aimed to evaluate the feasibility, safety, and preliminary efficacy of autologous ADSC injection in patients with complex postoperative enterocutaneous fistulas. Materials and Methods: Six patients (four males and two females) with persistent postoperative enterocutaneous fistulas were enrolled. Autologous adipose tissue was harvested via lipoaspiration from the abdominal wall or flank and processed in a GMP-certified laboratory to obtain a suspension containing 5–10 million viable ADSCs in 3–5 mL of isotonic solution. ADSCs were injected directly into the fistulous tract under ultrasound guidance, following CT image review. Clinical and radiologic follow-up was performed to assess closure and output reduction. Results: Four of the six patients (66.7%) achieved complete fistula closure, with no residual output and radiologic confirmation of healing within 4–12 weeks. One patient (16.7%) demonstrated a significant reduction in fistula output (>80%), while another (16.7%) showed minimal improvement and subsequently required surgical repair at 6 weeks. No complications related to ADSC administration were observed. Conclusions: Autologous ADSC therapy appears to be a feasible, safe, and minimally invasive option for managing complex postoperative enterocutaneous fistulas. These encouraging preliminary results—showing complete closure in two-thirds of treated patients—support further investigation through larger, controlled trials to validate these findings and optimize treatment protocols. Full article

Inflammatory bowel disease, encompassing ulcerative colitis and Crohn’s disease, is characterised by chronic immune-mediated inflammation and variable treatment response. Loss of drug efficacy due to underexposure, pharmacokinetic variability, and immunogenicity remains a key challenge. Therapeutic drug monitoring, using drug levels and anti-drug antibody measurements, is an important strategy for optimising the treatment of inflammatory bowel disease. It helps ensure adequate dosing and can distinguish between pharmacokinetic and mechanistic drug failure. Most evidence pertains to infliximab and adalimumab. Multiple factors influence drug pharmacokinetics, affecting both target drug levels and the doses required to achieve them. These include inflammatory burden, bodyweight, age, disease phenotype, and route of administration, all of which are important considerations for individualising treatment in inflammatory bowel disease. This narrative review explores how special clinical situations—acute severe ulcerative colitis, perianal fistulising Crohn’s disease, hypoalbuminaemia, extremes of body composition, pregnancy, paediatrics, and advanced age—alter drug pharmacokinetics and influence the utility and interpretation of therapeutic drug monitoring in inflammatory bowel disease. Full article

Background: Inflammatory bowel disease (IBD) can lead to zinc deficiency, which plays a critical role in immune function and tissue repair. This study aims to determine the prevalence, clinical characteristics, and impact of zinc deficiency in IBD patients. Methods: This is a retrospective study of patients aged ≥14 years with confirmed IBD and available zinc level measurement. Zinc deficiency was defined as a level <10.6 µmol/L. Primary outcomes included the prevalence of zinc deficiency and the characterization of the clinical profile of patients with zinc deficiency. Secondary outcomes included IBD-related hospitalizations, emergency room visits, surgeries, and complications (anemia, small bowel obstruction, new perianal disease, intra-abdominal abscess). Results: Among 447 patients (54.4% male; 79.2% Crohn’s disease) with a median age of 29 years (IQR: 22–38), 45.6% had zinc deficiency (83.8% Crohn’s disease). Zinc-deficient patients had higher C-reactive protein and fecal calprotectin (both p < 0.001) levels, and were more likely to be on corticosteroids (p = 0.04). Zinc deficiency was associated with higher rates of IBD-related hospitalizations (48.0% vs. 17.7%), surgeries (19.6% vs. 5.8%), complications (30.4% vs. 12.4%), and emergency room visits (40.2% vs. 17.3%) (all p < 0.001). Upon multivariate analysis, predictors of IBD-related hospitalization were zinc deficiency (OR 2.42, 95% CI 1.07–5.48, p = 0.03) and low albumin (OR 9.03, 95% CI 3.38–24.15, p < 0.001). Zinc deficiency was associated with IBD-related surgeries (OR 5.23, 95% CI 1.27–21.45, p = 0.02) and complications (OR 3.98, 95% CI 1.52–10.41, p = 0.005). Conclusions: Zinc deficiency is prevalent in patients with IBD, associated with a high inflammatory burden, and was linked to worse clinical outcomes after controlling for markers of inflammation. Full article

Background: Perianal Crohn’s disease (pCD) is one of the most disabling complications of inflammatory bowel disease, characterized by fistulas and abscesses that demand precise imaging for diagnosis, treatment planning, and follow-up. Magnetic resonance imaging (MRI) is considered the reference standard, but endoanal ultrasound (EAUS) with high-frequency 360° probes provide a readily available, cost-effective, and repeatable alternative. Methods: We performed a narrative review of the literature, evaluating studies on the EAUS technique, diagnostic applications, distinguishing features of Crohn’s-related fistulas, and comparative analyses with MRI. Consensus documents and structured reporting initiatives were also included. Results: EAUS provides high-resolution visualization of the anal sphincter complex and intersphincteric space, enabling the reliable detection of fistulas and abscesses. Characteristic features such as tract width > 4 mm, bifurcation, hyperechoic debris, the Crohn’s Ultrasound Fistula Sign (CUFS), and the rosary sign assist in differentiating Crohn’s from cryptoglandular fistulas. EAUS is well-suited for serial monitoring, perioperative seton guidance, and therapeutic decision-making. Emerging tools such as Doppler and shear wave elastography provide additional information on activity and fibrosis. MRI remains indispensable for supralevator disease, deep pelvic sepsis, and standardized activity indices. Comparative studies indicate similar sensitivity for simple fistulas, with MRI superior in complex cases; combining both modalities maximizes accuracy. Conclusions: EAUS is a practical and repeatable imaging tool that complements MRI in the multidisciplinary management of perianal Crohn’s disease. Advances such as 3D imaging, contrast enhancement, and elastography may enable validated activity scoring—for example, a future PEACE (Perianal Endosonographic Activity in Chron’s Evaluation) Index—further strengthening its role in longitudinal care. Full article

Background: Crohn’s disease (CD) is an inflammatory bowel disease (IBD) that is prevalent worldwide. It can affect any segment of the gastrointestinal tract, from the mouth to the anus. When CD affects the anus, perianal fistulizing disease develops. The management of perianal CD is challenging and may require morbid surgery when there is no response to medical therapy. The emergence of novel biologic therapies, namely tumor necrosis alpha (TNF-α) inhibitors, has proven to provide long-term relief and prevent disease-related complications. Perianal CD is, however, refractory or recurrent in up to 80% of patients. One of the reported options to manage perianal CD is hyperbaric oxygen therapy (HBOT), which aims at increasing tissue oxygen saturation in an attempt to promote repair and reverse local inflammation. Data on this approach is scant. Methods: A retrospective review was performed to identify patients with CD at the Mayo Clinic in Rochester who underwent HBOT for perianal disease between 2014 and 2023. Demographic and clinical data were reviewed, including the history of the disease, concomitant medical and surgical therapy and the need for fecal diversion. The HBOT regimen, including the number of sessions and clinical response, were reviewed. Results: Six patients aged from 19 to 60 years underwent HBOT for perianal CD. Two patients had a history of total proctocolectomy with ileal-anal pouch anastomosis (IPAA). All patients except one were on immunosuppressive medication including biologic agents. Four patients had fecal diversion with an ileostomy or colostomy. Patients received between 10 and 40 sessions of HBOT. Four patients reported symptomatic improvement. On physical examination and/or imaging assessment, improvement was noted in one patient. Progression of the perianal disease was noted in all other patients, with all except one requiring an operation in the following year. Conclusions: HBOT may provide symptomatic relief in some patients with refractory perianal CD, but data on its long-term efficacy remains limited. Full article

Background/Objectives: Crohn’s disease (CD) is one of the most frequent causes of short bowel syndrome (SBS), a severe clinical condition with huge morbidity and social costs. SBS occurs when, following intestinal resections, the remaining small bowel in continuity is less than 200 cm in length. Intestinal failure (IF) can complicate SBS when intravenous nutritional or electrolyte supplementation is required to maintain dietary needs. The primary aim of this study was to identify clinical predictive factors of SBS in a cohort of outpatients with CD. Methods: We conducted a prospective, single-center, cohort study enrolling consecutive CD outpatients at a tertiary-level inflammatory bowel disease center. Detailed demographic and clinical features were collected. Significant factors associated with the onset of SBS in the univariate analysis were input into a multivariate logistic regression model to identify independent predictors of SBS. Results: In total, 232 CD patients (52.6% male, median age 49 years [IQR 37–60]) were included: 24.6% of them were smokers; extraintestinal manifestations (EIMs) were present in 21.6% of patients; and 67.7% of patients had at least one intestinal resection (27% of them with more than one surgical intervention). At enrollment, 96.1% of patients were on advanced therapies, and considering the course of the disease, 24.6% of patients were exposed to ≥3 different advanced therapies. A total of 18 patients had SBS and 9 had IF. In univariate analysis, the following variables were statistically associated with the risk of developing SBS: disease duration (p < 0.001), upper gastrointestinal disease localization (L4) (p < 0.001), penetrating behavior (p = 0.023), perianal disease (p = 0.036), length of first intestinal resection (p < 0.001), shorter time elapsing from CD diagnosis to start the first advanced therapy (p < 0.001), and treatment with advanced therapy after first intestinal resection (p < 0.001). In multivariate analysis, disease duration (OR 1.083, 95% C.I. 1.025–1.145, p = 0.005) and L4 (OR 20.079, 95% C.I. 2.473–163.06, p = 0.005) were independently associated with the development of SBS. Conversely, the number of different advanced therapies before the onset of SBS was independently associated with a reduced risk of developing SBS (OR 0.247, 95% C.I. 0.107–0.58, p = 0.001). Conclusions: Our data identifies several clinical features that could possibly predict the development of SBS in CD. Further studies with a larger sample size are needed to confirm our findings. Full article

Perianal fistulising Crohn’s disease (pfCD) affects 1 in 5 Crohn’s patients and requires frequent MRI monitoring. Standard radiology reports are written for clinicians using technical language often inaccessible to patients, which can cause anxiety and hinder engagement. This study evaluates the feasibility and safety of AI-generated patient-friendly MRI fistula summaries to improve patient understanding and shared decision-making. MRI fistula reports spanning healed to complex disease were identified and used to generate AI patient-friendly summaries via ChatGPT-4. Six de-identified MRI reports and corresponding AI summaries were assessed by clinicians for hallucinations and readability (Flesch-Kincaid score). Sixteen patients with perianal fistulas were randomized to review either AI summaries or original reports and rated them on readability, comprehensibility, utility, quality, follow-up questions, and trustworthiness using Likert scales. Patients rated AI summaries significantly higher in readability (median 5 vs. 2, p = 0.011), comprehensibility (5 vs. 2, p = 0.007), utility (5 vs. 3, p = 0.014), and overall quality (4.5 vs. 4, p = 0.013), with fewer follow-up questions (3 vs. 4, p = 0.018). Clinicians found AI summaries more readable (mean Flesch-Kincaid 54.6 vs. 32.2, p = 0.005) and free of hallucinations. No clinically significant inaccuracies were identified. AI-generated patient-friendly MRI summaries have potential to enhance patient communication and clinical workflow in pfCD. Larger studies are needed to validate clinical utility, hallucination rates, and acceptability. Full article

The perianal skin is a unique “skin–gut” boundary that serves as a critical hotspot for the exchange and evolution of antibiotic resistance genes (ARGs). However, its role in the dissemination of antimicrobial resistance (AMR) has often been underestimated. To characterize the resistance patterns in the perianal skin environment of patients with perianal diseases and to investigate the drivers of AMR in this niche, a total of 51 bacterial isolates were selected from a historical strain bank containing isolates originally collected from patients with perianal diseases. All the isolates originated from the skin site and were subjected to antimicrobial susceptibility testing, whole-genome sequencing, and co-occurrence network analysis. The analysis revealed a highly structured resistance pattern, dominated by two distinct modules: one representing a classic Staphylococcal resistance platform centered around mecA and the bla operon, and a broad-spectrum multidrug resistance module in Gram-negative bacteria centered around tet(A) and predominantly carried by IncFIB and other IncF family plasmids. Further analysis pinpointed IncFIB-type plasmids as potent vehicles driving the efficient dissemination of the latter resistance module. Moreover, numerous unexplained resistance phenotypes were observed in a subset of isolates, indicating the potential presence of emerging and uncharacterized AMR threats. These findings establish the perianal skin as a complex reservoir of multidrug resistance genes and a hub for mobile genetic element exchange, highlighting the necessity of enhanced surveillance and targeted interventions in this clinically important ecological niche. Full article