Search Results (27)

Background: Endoscopic therapies for Crohn’s disease (CD) strictures, including endoscopic balloon dilation (EBD) and endoscopic stricturotomy (ESt), are less invasive interventions compared to surgery. ESt is advantageous for strictures that are longer, more fibrotic, or adjacent to anatomic structures requiring precision, and it has shown a high rate of surgery-free survival. Methods: We designed a microsimulation state-transition model comparing ESt to surgical resection for CD strictures. We calculated quality-adjusted life years (QALYs) over a 10-year time horizon; secondary outcomes included costs (in 2022 USD) and incremental cost-effectiveness ratios (ICERs). We used a societal perspective to compare our strategies at a willingness-to-pay (WTP) threshold of 100,000 USD/QALY. Sensitivity analyses, both deterministic and probabilistic, were performed. Results: The surgery strategy cost more than 2.5 times the ESt strategy, but resulted in nine more QALYs per 100 persons. The ICER for the surgery strategy was 308,787 USD/QALY; thus, the ESt strategy was determined more cost-effective. One-way sensitivity analyses showed that quality of life after ESt as compared to that after surgery, the likelihood of repeat intervention, and surgical mortality and cost were the most influential parameters shifting cost-effectiveness. Probabilistic sensitivity analyses favored ESt in most (65.5%) iterations. Conclusions: Our study finds endoscopic stricturotomy to be a cost-effective strategy to manage primary or anastomotic Crohn’s disease strictures. Post-intervention quality of life and probabilities of requiring repeated interventions exert most influence on cost-effectiveness. The decision between ESt and surgery should be made considering patient and stricture characteristics, preferences, and cost-effectiveness. Full article

Background: Urethral stricture disease involves fibrotic scarring that narrows the urethral lumen and can occur at any site. Sonourethrography (SUG) is increasingly used because it depicts both luminal anatomy and periurethral fibrosis, yet little is known about patient or lesion features that influence its diagnostic performance. Methods: We conducted a prospective single-center study of 170 men who underwent SUG before anterior urethroplasty between May 2016 and May 2021. Anthropometric data, comorbidities, and detailed ultrasonographic measurements were recorded and compared with intra-operative findings, which served as the reference standard. Accuracy was analyzed with Wald chi-square testing and Spearman correlation. Results: SUG length estimates matched intra-operative measurements in 139/170 strictures (81.8%). Length accuracy was higher in patients ≥ 60 years (89.2% vs. 77.0%, p = 0.03) and in those with type 2 diabetes (92.3% vs. 80.9%, p = 0.02) in conditions associated with pronounced spongiofibrosis that enhances echo contrast. Among stricture-specific factors, proximal location (63.6% vs. 84.5%, p = 0.01) and complete luminal occlusion (68.8% vs. 84.8%, p = 0.02) reduced precision, largely because deeper anatomy and absent saline flow hinder acoustic delineation. The Chiou ultrasonographic grade was the strongest determinant of performance; higher grades yielded clearer margins and better length estimation (p < 0.001). Conclusions: SUG is a reliable bedside technique for assessing anterior urethral strictures, but its accuracy varies with age, diabetes status, stricture site, degree of occlusion, and fibrosis grade. Recognizing these determinants allows clinicians to judge when SUG alone is sufficient and when complementary imaging or heightened caution is warranted. The findings support tailored imaging protocols and underscore the need for multi-center studies that include operators with diverse experience to confirm generalisability. Full article

Artificial intelligence (AI) is rapidly transforming imaging modalities in inflammatory bowel disease (IBD), particularly in endoscopy and ultrasound. Despite their critical roles, both modalities are challenged by interobserver variability, subjectivity, and accessibility issues. AI offers significant potential to address these limitations by enhancing lesion detection, standardizing disease activity scoring, and supporting clinical decision-making. In endoscopy, deep convolutional neural networks have achieved high accuracy in detecting mucosal abnormalities and grading disease severity, reducing observer dependency and improving diagnostic consistency. AI-assisted colonoscopy systems have also demonstrated improvements in procedural quality metrics, including adenoma detection rates and withdrawal times. Similarly, AI applications in intestinal ultrasound show promise in automating measurements of bowel wall thickness, assessing vascularity, and distinguishing between inflammatory and fibrotic strictures, which are critical for tailored therapy decisions. Video capsule endoscopy has likewise benefited from AI, reducing interpretation times and enhancing the detection of subtle lesions. Despite these advancements, implementation challenges, including dataset quality, standardization, AI interpretability, clinician acceptance, and regulatory and ethical considerations, must be carefully addressed. The current review focuses on the most recent developments in the integration of AI into experimental designs, medical devices, and clinical workflows for optimizing diagnostic accuracy, treatment strategies, and patient outcomes in IBD management. Full article

Crohn’s disease (CD) is a chronic inflammatory disorder of the gastrointestinal tract that often leads to intestinal fibrosis, an irreversible complication associated with strictures and the need for surgical intervention. Fibrosis occurs due to prolonged inflammation and abnormal wound healing, involving complex interactions between immune cells, mesenchymal cells, cytokines, and the gut microbiota. Key fibrogenic mechanisms include the activation of fibroblasts and myofibroblasts, cytokine signaling, and disrupted turnover of the extracellular matrix. Advancements in imaging techniques, such as MRI and CT enterography, have improved the detection and monitoring of fibrosis. Additionally, molecular techniques targeting fibroblast activation proteins show promise as a new imaging method. However, there are currently no approved anti-fibrotic therapies for CD. Emerging strategies focus on key pathways and novel therapeutic targets, including growth factor modulators, intracellular enzyme and kinases modulators, and interventions targeting the modulation of inflammation and extracellular matrix, which are being evaluated in preclinical and clinical settings. This review discusses the pathophysiology, diagnostic advancements, and therapeutic perspectives related to intestinal fibrosis in CD, emphasizing the urgent need for targeted anti-fibrotic therapies to prevent long-term complications and improve the life quality of patients. Full article

Esophageal fibrotic remodeling is a major complication of chronic inflammation in eosinophilic esophagitis (EoE) and represents one of the main determinants of symptoms in adult patients with EoE, with a remarkable impact on patients’ quality of life and the healthcare system. Esophageal fibrotic remodeling is diagnosed through upper gastrointestinal endoscopy, radiological studies, and a functional luminal imaging probe. However, diagnostic underestimation of esophageal strictures and suboptimal adherence to EoE guidelines still represent limitations of current clinical practice. Combined with medical therapy and/or elimination diets, endoscopic dilation remains the cornerstone treatment for esophageal strictures and rings, offering a safe and effective option for managing obstructive symptoms. Different modalities are available for esophageal endoscopic dilation of EoE, including mechanical and balloon dilators. Mechanical dilators provide tactile feedback during the procedure and exert longitudinal and radial forces. In contrast, balloon dilators apply a purely radial force and enable direct visualization of the esophageal mucosa during the procedure. Both mechanical and balloon dilators are safe and effective, with no single modality demonstrating clear superiority. Consequently, the choice of dilation technique is guided by stricture characteristics, the expertise of the endoscopist, and considerations related to the financial and environmental sustainability of the devices. This review aims to summarize the most relevant evidence on the endoscopic evaluation and dilation of fibrostenotic complications in EoE, also providing practical guidance for clinicians to optimize the endoscopic management of these patients. Full article

Inflammatory bowel diseases (IBD) are chronic disorders characterized by persistent inflammation of the gastrointestinal tract. Despite advances in treatment, a significant proportion of patients remain refractory to current therapies and develop complications, particularly fibrosis, leading to strictures and fistulae. Tumor necrosis factor-like ligand 1A (TL1A) has emerged as a promising new target for IBD treatment, due to its dual role in inflammatory and fibrotic pathways. TL1A, acting through its receptor death receptor 3 (DR3), orchestrates mucosal inflammation by enhancing T-cell activation and promoting pro-inflammatory mediator secretion. TL1A also drives intestinal fibrosis by activating fibroblasts and increasing collagen deposition. Clinical trials evaluating anti-TL1A monoclonal antibodies have shown encouraging efficacy and safety, with significant improvements in clinical remission rates, endoscopic healing, and histologic outcomes. Beyond IBD, TL1A overexpression has been implicated in other immune-mediated inflammatory diseases, highlighting its broader therapeutic potential. This review explores TL1A’s role in IBD pathogenesis, the latest clinical trial data, and its involvement in extraintestinal inflammatory disorders, underscoring its potential as a novel precision-medicine target across multiple diseases. Full article

Intestinal fibroblasts are pivotal players in maintaining tissue homeostasis and orchestrating responses to injury and inflammation within the gastrointestinal (GI) tract. Fibroblasts contribute significantly to the pathogenesis of inflammatory bowel disease (IBD), including Crohn’s disease and ulcerative colitis (UC), by secreting pro-inflammatory cytokines, modulating immune cell activity, and promoting fibrosis. In addition, fibroblasts play crucial roles in tissue repair and regeneration following acute injury or chronic inflammation. The dysregulation of fibroblast functions can lead to fibrotic complications, such as intestinal strictures and obstruction, which are common in advanced stages of IBD. Understanding the complex interplay between fibroblasts and other cell types in the intestine is essential to elucidate the underlying mechanisms of intestinal diseases and identify novel therapeutic targets. Future research aimed at deciphering the heterogeneity of intestinal fibroblasts and their dynamic roles in disease progression holds promise for the development of precision therapies to mitigate fibrosis and inflammation in intestinal disorders. Full article

A retrospective analysis was conducted to investigate how a bright luminal sign on high b-value diffusion-weighted imaging (DWI) could be considered as a new biomarker for identifying fibrotic strictures in Crohn’s disease (CD). Fibrotic strictures, due to excessive deposition of extracellular matrix following chronic inflammatory processes, can be difficult to distinguish from inflammatory strictures using endoscopy. This study was performed on 65 patients with CD who underwent MRE, and among them 32 patients showed the bright luminal sign on high b-value DWI. DWI findings were compared to pre- and post-contrast MRE data. Luminal bright sign performance results were calculated using a confusion matrix, the relationship between categorical variables was assessed by the χ2 test of independence, and the Kruskal–Wallis test (ANOVA) was used for the assessment of statistical significance of differences between groups. The results indicated a high sensitivity (90%) and specificity (85%) of the bright luminal sign for fibro-stenotic CD and a significant correlation between DWI luminal brightness and markers such as the homogeneous enhancement pattern (p < 0.001), increase in enhancement percentage from 70 s to 7 min after gadolinium injection (p < 0.001), and submucosal fat penetration (p = 0.05). These findings indicate that DWI hyperintensity can be considered as a good non-invasive indicator for the detection of severe intestinal fibrosis and may provide an efficient and accurate method for assessing fibrotic strictures. This new non-invasive biomarker could allow an early diagnosis of fibrotic stricture, delaying the onset of complications and subsequent surgery. Moreover, further evaluations through larger prospective trials with histopathological correlation are needed to confirm these results and completely determine the clinical benefits of DWI in treating CD. Full article

Background: Crohn’s disease (CD) is a complex systemic entity, characterized by the progressive and relapsing inflammatory involvement of any part of the gastrointestinal tract. Its clinical pattern may be categorized as penetrating, stricturing or non-penetrating non-stricturing. Methods: In this paper, we performed a database search (Pubmed, MEDLINE, Mendeley) using combinations of the queries “crohn”, “stricture” and “elastography” up to 19 June 2024 to summarize current knowledge regarding the diagnostic utility of ultrasound (US) and magnetic resonance (MR) elastography techniques in the evaluation of stricturing CD by means of an assessment of the transmural intestinal fibrosis. We decided to include papers published since 1 January 2017 for further evaluation (n = 24). Results: Despite growing collective and original data regarding numerous applications of mostly ultrasound elastography (quantification of fibrosis, distinguishing inflammatory from predominantly fibrotic strictures, assessment of treatment response, predicting disease progression) constantly emerging, to date, we are still lacking a uniformization in both cut-off values and principles of measurements, i.e., reference tissue in strain elastography (mesenteric fat, abdominal muscles, unaffected bowel segment), units, not to mention subtle differences in technical background of SWE techniques utilized by different vendors. All these factors imply that ultrasound elastography techniques are hardly translatable throughout different medical centers and practitioners, largely depending on the local experience. Conclusions: Nonetheless, the existing medical evidence is promising, especially in terms of possible longitudinal comparative studies (follow-up) of patients in the course of the disease, which seems to be of particular interest in children (lack of radiation, less invasive contrast media) and terminal ileal disease (easily accessible). Full article

Background: Crohn’s disease (CD) is a chronic, progressive inflammatory condition, involving primarily the bowel, characterized by a typical remitting–relapsing pattern. Despite endoscopy representing the reference standard for the diagnosis and assessment of disease activity, radiological imaging has a key role, providing information about mural and extra-visceral involvement. Methods: Computed Tomography and Magnetic Resonance Imaging are the most frequently used radiological techniques in clinical practice for both the diagnosis and staging of CD involving the small bowel in non-urgent settings. The contribution of imaging in the management of CD is reported on by answering the following practical questions: (1) What is the best technique for the assessment of small bowel CD? (2) Is imaging a good option to assess colonic disease? (3) Which disease pattern is present: inflammatory, fibrotic or fistulizing? (4) Is it possible to identify the presence of strictures and to discriminate inflammatory from fibrotic ones? (5) How does imaging help in defining disease extension and localization? (6) Can imaging assess disease activity? (7) Is it possible to evaluate post-operative recurrence? Results: Imaging is suitable for assessing disease activity, extension and characterizing disease patterns. CT and MRI can both answer the abovementioned questions, but MRI has a greater sensitivity and specificity for assessing disease activity and does not use ionizing radiation. Conclusions: Radiologists are essential healthcare professionals to be involved in multidisciplinary teams for the management of CD patients to obtain the necessary answers for clinically relevant questions. Full article

Bowel strictures are well recognized as one of the most severe complications in Crohn’s disease, with variable impacts on the prognosis and often needing surgical or endoscopic treatment. Distinguishing inflammatory strictures from fibrotic ones is of primary importance due to the different therapeutic approaches required. Indeed, to better understand the pathogenesis of fibrosis, it is crucial to investigate molecular processes involving genetic factors, cytokines, alteration of the intestinal barrier, and epithelial and endothelial damage, leading to an increase in extracellular matrix synthesis, which ultimately ends in fibrosis. In such a complex mechanism, the gut microbiota also seems to play a role. A better comprehension of molecular processes underlying bowel fibrosis, in addition to radiological and histopathological findings, has led to the identification of high-risk patients for personalized follow-up and testing of new therapies, primarily in preclinical models, targeting specific pathways involving Transforming Growth Factor-β, interleukins, extracellular matrix balance, and gut microbiota. Our review aims to summarize current evidence about molecular factors involved in intestinal fibrosis’ pathogenesis, paving the way for potential diagnostic biomarkers or anti-fibrotic treatments for stricturing Crohn’s disease. Full article

Background and Objectives: Despite the fact that biologic drugs have transformed inflammatory bowel disease (IBD) treatment, addressing fibrosis-related strictures remains a research gap. This study explored the roles of cytokines, macrophages, and Krüppel-like factors (KLFs), specifically KLF4, in intestinal fibrosis, as well as the interplay of KLF4 with various gut components. Materials and Methods: This study examined macrophage subtypes, their KLF4 expression, and the effects of KLF4 knockdown on macrophage polarization and cytokine expression using THP-1 monocyte models. Co-culture experiments with stromal myofibroblasts and a conditioned medium from macrophage subtype cultures were conducted to study the role of these cells in intestinal fibrosis. Human-induced pluripotent stem cell-derived small intestinal organoids were used to confirm inflammatory and fibrotic responses in the human small intestinal epithelium. Results: Each macrophage subtype exhibited distinct phenotypes and KLF4 expression. Knockdown of KLF4 induced inflammatory cytokine expression in M0, M2a, and M2c cells. M2b exerted anti-fibrotic effects via interleukin (IL)-10. M0 and M2b cells showed a high migratory capacity toward activated stromal myofibroblasts. M0 cells interacting with activated stromal myofibroblasts transformed into inflammatory macrophages, thereby increasing pro-inflammatory cytokine expression. The expression of IL-36α, linked to fibrosis, was upregulated. Conclusions: This study elucidated the role of KLF4 in macrophage polarization and the intricate interactions between macrophages, stromal myofibroblasts, and cytokines in experimental in vitro models of intestinal fibrosis. The obtained results may suggest the mechanism of fibrosis formation in clinical IBD. Full article

Inflammatory bowel disease (IBD), especially Crohn’s disease (CD), characterized by a chronic inflammatory process and progressive intestinal tissue damage, leads to the unrestrained proliferation of mesenchymal cells and the development of bowel strictures. Complications induced by fibrosis are related to high rates of morbidity and mortality and lead to a substantial number of hospitalizations and surgical procedures, generating high healthcare costs. The development of easily obtained, reliable fibrogenesis biomarkers is essential to provide an important complementary tool to existing diagnostic and prognostic methods in IBD management, guiding decisions on the intensification of pharmacotherapy, proceeding to surgical methods of treatment and monitoring the efficacy of anti-fibrotic therapy in the future. The most promising potential markers of fibrosis include cartilage oligomeric matrix protein (COMP), hepatocyte growth factor activator (HGFA), and fibronectin isoform- extra domain A (ED-A), as well as antibodies against granulocyte macrophage colony-stimulating factor (GM-CSF Ab), cathelicidin (LL-37), or circulatory miRNAs: miR-19a-3p and miR-19b-3p. This review summarizes the role of genetic predisposition, and risk factors and serological markers potentially contributing to the pathophysiology of fibrotic strictures in the course of IBD. Full article

Eosinophilic esophagitis (EoE) is a chronic, progressive, type 2 inflammatory disease with increasing global prevalence. An eosinophil-predominant inflammation that permeates the epithelium and deeper esophageal layers characterizes the disease. Several cytokines, mainly derived from inflammatory T-helper 2 (Th2) cells and epithelial cells, are involved in perpetuating inflammatory responses by increasing surface permeability and promoting tissue remodeling characterized by epithelial–mesenchymal transition (EMT) and collagen deposition. This leads to esophageal strictures and narrow caliber esophagi, which are proportional a patient’s age and untreated disease length. Pathophysiological mechanisms leading to EoE have been described in recent years, and transforming growth factor beta (TGF)-beta have been involved in fibrotic phenomena in EoE. However, evidence on the dependence of these phenomena on TGF-beta is scarce and contradictory. This review provides state-of-the art knowledge on intimate mechanisms of esophageal fibrosis in EoE and its clinical consequences. Full article

Crohn’s disease (CD) is a chronic inflammation of the digestive tract, and it frequently affects young patients. It can involve any intestinal segment, even though it frequently affects the distal ileum. Up to 80% of patients with CD present with inflammatory behavior, and 5% to 28% develop stricturing disease. Based on the predominant mechanism causing them, strictures can be categorized as inflammatory, fibrotic, or mixed. Determining the relative amounts of inflammation and fibrosis in a stricture can influence treatment decisions. Imaging is an extremely useful tool in patients with small bowel stricturing CD to confirm the diagnosis and to evaluate disease characteristics, usually using CT or MRI. The aim of this paper is to describe how imaging can evaluate a patient with small bowel CD stricture. Full article