Fletcher, Joel G.

ABSTRACT Background Treatment options for medically‐refractory faecal incontinence ( FI )—including anorectal biofeedback, dextranomer injection, and sacral nerve stimulation—are limited and outcomes are often suboptimal. Anal or vaginal insert devices are infrequently used. Aims We evaluated the safety and effectiveness of a new anal insert device (StaySure) in patients with FI. Methods Patients with FI for ≥ 6 months and ≥ 4 moderate or large FI episodes during a 4‐week baseline entered a 2–4 week fitting/run‐in period to individualise device size (10 or 13 mm) followed by a 4‐week treatment period. Outcomes included effectiveness, safety, and quality of life (QoL). The primary outcome was the proportion achieving a ≥ 50% reduction in FI frequency. Results Of 124 enrolled patients, 98, 71, and 61 progressed through the baseline, fitting/run‐in, and treatment phases respectively, with few exclusions due to device intolerance. In the intent‐to‐treat cohort of 59 participants (93% women), mean ( SD ) number of days with FI declined from 13.2 (7.0) to 6.3 (6.9), and FI weekly episodes declined from 5.4 (6.9) to 2.1 (5.1) (69% reduction; p < 0.001) with similar results for both device sizes. The primary endpoint was achieved in 76.3% of participants; 54.2% achieved ≥ 75% reduction. The FIQoL overall score increased from a mean ( SD ) of 1.9 (0.6) to 2.3 (0.6) ( p < 0.001), indicating improved QoL . Improvements in FI frequency, FIQoL exceeded minimal clinically important difference thresholds, confirming clear clinical benefit. No treatment‐related serious adverse events were reported. Conclusions The StaySure anal insert device is safe, well tolerated, and effective in reducing FI in patients with moderate to severe symptoms refractory to conservative therapies. Trial Registration ClinicalTrials.gov identifier: NCT03898778

Due to increasingly nuanced Crohn disease therapy selection and disease evaluation, radiologic assessment of transmural healing, although aspirational, may be more complete than endoscopic assessment of mucosal healing, which is the current treatment target.

Background Failure of conventional imaging to detect pancreatic ductal adenocarcinoma (PDA) at its visually occult pre-diagnostic stage is a primary barrier to improving its otherwise poor rate of survival. Objective To develop and validate the Radiomics-based Early Detection MODel (REDMOD), an AI framework to identify subvisual radiomic signatures of pre-diagnostic PDA on standard-of-care CT. Designs REDMOD was trained on a multi-institutional cohort (n=969; 156 pre-diagnostic, 813 control) and tested on an independent set (n=493; 63 pre-diagnostic, 430 control), simulating a low prevalence (~1:6) early detection paradigm. The fully automated framework couples AI-driven segmentation with a heterogeneous ensemble architecture trained on a 40-feature radiomic signature derived from Synthetic Minority Over-sampling Technique (SMOTE)-balanced data. A tunable Youden Index-optimised classification threshold enables performance calibration without retraining. Validation included direct comparison with radiologists, longitudinal test–retest analysis and external specificity validation across two independent cohorts (n=539 and n=80). Results On an independent test set (n=493), REDMOD identified occult PDA (AUC 0.82; 73.0% sensitivity) at a median 475-day lead time. This represented nearly twofold higher sensitivity than radiologists (38.9%; p<0.001), which grew to nearly threefold (68.0% vs 23.0%) at >24 months lead time. REDMOD showed strong longitudinal stability (90–92% concordance) and generalisable specificity across multi-institutional (81.3%; n=539) and public (87.5%; n=80) datasets. Mechanistic analyses confirmed predictive power derived principally from multi-scale wavelet-filtered textural features (90% of selected signature), which outperformed unfiltered features (AUC 0.82 vs 0.74; p=0.007) in capturing subvisual architectural disruptions. Conclusions REDMOD is an automated, mechanistically grounded, longitudinally stable, externally validated AI that surpasses radiologists for PDA detection at its visually occult pre-diagnostic stage. These attributes position it for prospective validation in high-risk cohorts, a necessary step towards shifting the paradigm from late-stage symptomatic diagnosis to proactive pre-clinical interception.

Abstract Photon-counting detector CT (PCD-CT) directly detects individual photons and measures their energies, enabling the acquisition of multi-energy data from a single x-ray source with higher spatial resolution, thereby allowing visualization of smaller arteries and veins and other important imaging features not seen at conventional CT. It also substantially reduces calcium and stent blooming artifacts. Appropriate patient selection and task-based optimization of acquisition, reconstruction, and interpretation are critical to realize these benefits. Vascular imaging examinations for which early evidence shows that PCD-CT demonstrates higher diagnostic performance compared to conventional CT include coronary CT angiography (CTA) for evaluation of partially calcified plaques or stents, peripheral runoff CTA, detection of cerebrospinal fluid-venous fistulas, and head CTA for evaluation of small intracranial vessels and aneurysms. Current limitations include excessive image noise with the sharpest reconstruction kernels and challenges when adapting conventional CT protocols (eg, requiring sharper kernels, thinner slices, higher matrices, tailored scan modes) to achieve time-efficient image reconstruction and hanging protocols. New solutions and directions will include deep-learning-based image noise reduction, improved spectral separation, strategic triage of specific patient populations to PCD-CT systems, and subspecialty clinical practice recommendations for this new technology.

Abstract Background & Aims Stricturing Crohn’s disease (CD) is a significant problem, and no selective anti-fibrotic therapies are available. Anti-inflammatory approaches are the mainstay of medical treatment. However, data on the efficacy of ustekinumab (USTE) in ileal stricturing CD are lacking. Our aim was to assess its efficacy in this setting. Methods We performed an international multicenter observational cohort study evaluating adult CD patients who received USTE within 6 months of imaging-confirmed symptomatic stricturing small bowel disease. Outcomes were rates of endoscopic balloon dilation (EBD), surgery, intervention (defined as the composite need for EBD or surgery), recurrent obstructive symptoms, and USTE persistence. Results Fifty-seven patients were included (51% female, median age 43 years). Median follow-up was 17 months. Intervention rates were 35%, 45%, and 69% of patients, at 12, 24, and 48 months, respectively. USTE persistence was 78%, 76%, and 52% at 12, 24, and 48 months. Estimated obstructive symptoms rates were 31% and 49% at 12 and 24 months, respectively. EBD within 6 months prior to starting USTE was associated with an increased risk of intervention. Increased bowel wall thickness on imaging, prior biologic use, and obstructive symptom duration were associated with USTE discontinuation. Occurrence of obstructive symptoms during treatment was associated with prior biologic use, EBD within 6 months of starting USTE, and a lower BMI. Conclusions USTE appears to be an appropriate medical option in biologic-experienced CD patients with ileal strictures. Further prospective data are needed to better define outcomes and predictors of response in this setting.

Abstract Dysphagia is defined as a subjective sensation of difficulty swallowing and can result from oropharyngeal or esophageal etiologies based upon patient symptoms. Dysphagia affects approximately 16% of adults in the general population, with prevalence increasing with age. Esophagogastroduodenuoscopy (EGD) is initially performed to assess for structural abnormalities resulting in esophageal dysphagia. However, if EGD reveals no pathologic abnormalities, high-resolution manometry (HRM) and barium esophagography are performed in order to assess for underlying causes of dysmotility. Esophageal motility disorders (EMDs) are an underrecognized cause of dysphagia and can be characterized by impaired esophageal peristalsis or lower esophageal sphincter dysfunction. High-resolution manometry (HRM) measures key metrics such as integrated relaxation pressure (IRP), which is the deglutitive relaxation across the LES, and metrics of esophageal body peristalsis based on distal contractile integral (DCI) and distal latency (DL). The Chicago Classification version 4 (CCv4.0), published in 2021, provides a standardized classification scheme for differentiating EMDs using metrics from HRM. Additionally, barium esophagography has remained an important adjunctive diagnostic modality, as this may identify strictures, neoplasms, or hiatal hernias, but can also identify major motility disorders such as achalasia and distal esophageal spasm. The combined use of HRM with timed barium esophagram can enhance the diagnostic accuracy of EMDs, particularly when HRM demonstrates inconclusive findings. Therefore, radiologists should be familiar with how imaging findings from barium esophagram integrate with findings noted on HRM. The aim of this review is to highlight the findings of EMDs noted on HRM in conjunction with barium esophagography, thereby illustrating characteristic patterns of primary and secondary EMDs.

Abstract Background Colonic strictures in Crohn’s disease (CD) are an important, but understudied clinical problem. Cross-sectional imaging modalities such as computed tomography (CT), magnetic resonance imaging (MRI), and intestinal ultrasound (IUS) effectively assess the small bowel in CD allowing for the diagnosis of strictures. However, radiologic definitions of colonic strictures and their diagnostic accuracy have not been developed. Endoscopic definitions of colonic strictures are the most well-described. Aims We aimed to systematically review available data to summarize definitions, diagnosis and differentiation between inflammation and fibrosis of colonic strictures on endoscopy, CT, MR, and IUS Methods We conducted a systematic review following PRISMA guidelines using MEDLINE, Scopus, CINAHL, and CENTRAL databases from inception to Oct 6, 2024 to identify literature with diagnostic imaging that included patients with colonic CD strictures. To distinguish fibrosis from inflammation, only studies comparing endoscopy or imaging to a full thickness histologic gold standard were included. Two stage screening was completed in duplicate, and risk of bias was assessed using QUADAS-2 Results 46 studies were eligible for inclusion. Definitions for colonic strictures on CT, MR, and IUS are heterogeneous with combinations of bowel wall thickness, luminal narrowing, and pre-stenotic dilation with no clear cut offs. Endoscopic definitions commonly included lack of colonoscope passage through a narrowed lumen. The diagnostic accuracy of colonic strictures on imaging to detect inflammation and fibrosis against a gold standard of endoscopy or surgical resection is unclear as direct comparisons are few. Meta-analyses were not conducted due to methodological heterogeneity of grading fibrosis and statistical heterogeneity of sensitivity, specificity, and accuracy of colonic stricture diagnoses limited by pooling with small bowel strictures in the studies Conclusions This systematic review describes a lack of definitions for the diagnosis of CD colonic strictures particularly on diagnostic imaging, and the limitations with the current available data to differentiate inflammation from fibrosis. Although bowel wall thickening, luminal narrowing, and pre-stenotic dilation are recognized as hallmark features of small bowel strictures, their adaptation to the colon requires further assessment. Definitions for colonic strictures should likely include imaging combined with endoscopy. Future endeavors are required to develop a consensus to define and diagnose colonic strictures on these modalities Funding Agencies None

Abstract Background Colonic strictures in Crohn’s disease (CD) present a complex and relatively underexplored clinical issue. Imaging modalities such as computed tomography (CT), magnetic resonance imaging (MRI), and intestinal ultrasound (IUS), have established criteria for evaluating small bowel CD strictures. However, radiologic definitions of benign colonic strictures and their diagnostic accuracy are not well-developed. Endoscopic definitions of colonic strictures are the most well-described. We conducted a systematic review to summarize definitions, diagnosis, and identification of inflammation and fibrosis of colonic strictures on endoscopy, CT, MR, and IUS. Methods A systematic review following PRISMA guidelines, from inception to October 6, 2024, was conducted using MEDLINE, Scopus, CINAHL, and CENTRAL databases to identify literature on diagnostic imaging of patients with colonic CD strictures. Only studies with comparison to endoscopy or imaging to a full-thickness histologic gold standard to differentiate fibrosis from inflammation were included. Two stage screening was completed in duplicate, and risk of bias was assessed using QUADAS-2. Results 46 studies were eligible for inclusion of 4623 abstracts screened. Definitions of colonic strictures on CT, MR, and IUS were highly variable with combinations of bowel wall thickness, luminal narrowing, and pre-stenotic dilation. Endoscopic definitions of colonic strictures were the most consistently reported as lack of passage of a colonoscope through a narrowed lumen. Diagnostic imaging definitions used various combinations of increased bowel wall thickness, luminal narrowing, and pre-stenotic dilation with no clear cutoffs. Few studies directly compared imaging features with histologic or endoscopic gold standards, limiting evaluation of diagnostic accuracy. Meta-analyses were not conducted due to methodological heterogeneity of grading fibrosis across studies. In addition, statistical heterogeneity of sensitivity, specificity, and accuracy of colonic stricture diagnoses was limited by pooling with small bowel strictures in the studies. Conclusion This systematic review highlighted the absence of standardized definitions for diagnosing colonic Crohn’s disease strictures, particularly on diagnostic imaging, and the limited data distinguishing inflammatory from fibrotic components. Bowel wall thickening, luminal narrowing, and pre-stenotic dilation are key features of small bowel strictures, but their relevance to the colon requires further assessment. Establishing standardized definitions for colonic strictures that incorporate both endoscopic and imaging modalities is essential to advancing the field. Conflict of interest: Dr. Lu, Cathy: Advisory board - Abbvie, Johnson and Johnson, Takeda, Ferring, Merck, Celltrion, Lilly, Pfizer, Pendopharm, Agomab. Research Funding - Abbvie, Helmsley Charitable Trust, Alberta Innovates Dhaliwal, Ravdip: No conflict of interest Kellar, Amelia: No conflict of interest Rowan, Catherine: No conflict of interest St-Pierre, Joelle: Consultant for Pfizer, Abbvie, Eli Lilly and Pendopharm, and speaker for Takeda. Ernest-Suárez, Kenneth: Consulting/Advisory Board fees: Abbvie, AstraZeneca, Johnson & Johnson, Pfizer, Ferring, Sandoz, SatisfAI, Takeda O’Brien, Maureen: No conflict of interest Rosentreter, Ryan: No conflict of interest Gulhati, Vishrut: No conflict of interest Baker, Mark: No conflict of interest Bettenworth, Dominik: DB is on the advisory board or consultant for AbbVie, Amgen, Arena, Atheneum, BNG Service GmbH, Bristol Myers Squibb, CED-Service GmbH, Celltrion, Doctorflix, DGVS, Diaplan, Else Kröner-Fresenius Foundation, Falk Foundation, Galapagos, Guidepoint, Impulze, Ferring, Janssen Cilag, Lilly, Medical Tribune, MedTriX, MSD, Mylan, Onkowissen, Pharmacosmos, Pfizer, Roche, Sandoz, Takeda, Tetrameros, Thieme, Tillotts Pharma, UCB Biopiharma, Viatris and Vifor Pharma. Bruining, David: Advisory board fees from Janssen Bari, Dane: Grant from Helmsley Charitable Trust speaker honorarium from Siemens Healthineers support for attending meetings or travel from Siemens Healthineers member of the Olympus advisory board co-chair Society of Abdominal Radiology (SAR) Inflammatory Bowel Disease Disease Focused Panel (IBD DFP) and SAR Photon-Counting Detector CT Emerging Technology Commission and chair of the Society for Advanced Body Imaging Scientific Committee. Dillman, Jonathan: Grants from Philips Healthcare, GE HealthCare, Motilent, Perspectum, Guerbet, and Bracco. El Ouali, Sara: Speaker and/or consulting fees from Takeda, Eli Lilly, Janssen, Abbvie. Fletcher, John: Grant supports from Siemens Healthineers Gordon, Ilyssa: Grants to institution from Morphic Therapeutics, Alimentiv, Pliant Therapeutics, and UCB patent pending with Case Western Reserve University on radiomics signatures Jairath, Vipul: Consulting Fees: Abbvie, Alimentiv, Amgen, Anaptys Bio, Asahi Kasei, Asieris, Astra Zeneca, Attovia, Blackbird Labs, BMS, Boehringer Ingleheim, Biomebank, Caldera, Calluna, Catalytic Health, Celltrion, Ensho, Enthera, Exeliome Biosciences, Ferring, Fresenius Kabi, Gilead, Granite Bio, GSK, Janssen, Lilly, Merck, Mountainfield, MRM Health, Nxera, Organon, OSE Immunotherapeutics, Pendopharm, Pioneering Medicine, Pfizer, Prometheus, Roche/Genentech, Sanofi, SCOPE, Shattuck Labs, Sorriso, Spyre, Synedgen, Takeda, Teva, Tillotts, Union Therapeutics, Ventus, Ventyx, Vividion, Xencor, Zealand Pharma. Feagan, Brian Gordon: Consulting Fees: AbbVie, Abivax, Adaxion, Adiso, AgomAB Therapeutics, Akros, Alira Health, Ally Bridge Group, Apini Therapeutics, Argenx, Attovia Tx, Avoro Capital Advisors, Belmore Law, Biora Therapeutics, Blackbird Laboratories, Boehringer-Ingelheim, BMS, Boxer Capital, Celgene/BMS, Clarivate, Connect Biopharm, EcoR1, Eli Lilly, Ensho Therapeutics, Equillium, Evida, Enveda, Evommune Inc. Faes Farma, First Wave, Forbion, Galapagos, Genentech/Roche, General Atlantic, Genesis Therapeutics, Gerson Lehrman Group, Gilead, Guidepoint, Imhotex, ImiDomics, Immunic Therapeutics, Janssen, Japan Tobacco Inc., LifeMine Therapeutics, Mage Biologics, Merck, Mirador Therapeutics, Mobius Care, Monte Rosa Tx, Morphic Therapeutics, Nimbus Therapeutics, Novartis, Nxera, OncoC3, Palisade Bio, Pendopharm, Pfizer,Q32 Bio, REDX, Roche, Sanofi, Sobi, Sorriso, Spyre Therapeutics, Sun Pharma, Surrozen Inc., Synedgen, Takeda, Tegus Inc., Teva, Tillotts, Trex Bio, TR1X Inc. TVM Lifesciences, Ventyx Biosciences, Versant Ventures, Vida Ventures, Ysios Capital, Zagbio Stock Shareholder: Connect Biopharm, EnGene, Evida, SRT, Imidomics, Enveda Rieder, Florian: Personal Fees: Adiso, Adnovate, Agomab, Allergan, AbbVie, Arena, Astra Zeneca, Boehringer-Ingelheim, Celgene/BMS, Celltrion, CDISC, Celsius, Cowen, Ferring, Galapagos, Galmed, Genentech, Gilead, Gossamer, Granite, Guidepoint, Helmsley, Horizon Therapeutics, Image Analysis Limited, Index Pharma, Landos, Jannsen, Koutif, Mestag, Metacrine, Mopac, Morphic, Organovo, Origo, Palisade, Pfizer, Pliant, Prometheus Biosciences, Receptos, RedX, Roche, Samsung, Sanofi, Surmodics, Surrozen, Takeda, Techlab, Teva, Theravance, Thetis, UCB, Ysios, 89Bio

Abstract This article provides an overview of deep-learning–based techniques in CT image reconstruction and processing (referred to as “DLR”), covering technical implementations, performance evaluation, radiation dose reduction, and future perspectives. DLR methods can be categorized into projection-space, projection-to-image-space, image-space, and various hybrid techniques, with applications such as noise reduction, artefact correction, and spatial resolution enhancement. Performance evaluations include phantom-based studies, patient image-based studies, and virtual imaging trials. These evaluation studies demonstrated that DLR can effectively reduce image noise while preserving an image texture like in traditional filtered-backprojection (FBP) images, although the extent of radiation dose reduction varies widely depending on the study and the specific diagnostic task. Challenges remain in low-contrast lesion detection and characterization, where dose reduction may still be less than 50% compared to traditional reconstruction methods. Additionally, the potential for DLR methods to generate false structures or “hallucinations,” especially at low radiation doses, emphasizes the need for effective monitoring and mitigation strategies from both technical and clinical perspectives. Quantitative, accurate, and efficient evaluation techniques, such as virtual image trial-based methods, can be explored to help optimize these algorithms for reducing radiation dose and enhancing diagnostic performance.