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A SYSTEMATIC REVIEW AND META-ANALYSIS OF TEST PERFORMANCE IN RANDOMIZED CONTROLLED TRIALS FOR COLONOSCOPY SCREENING FOR COLORECTAL CANCER

Chisato Hamashima 1, Teruhiko Terasawa 2, Koichiro Abe 1, Satoyo Hosono 3, Seiju Sasaki 4, Takafumi Katayama 5, Toshihiro Tadano 6, Keika Hoshi 7

Affiliations

1 Teikyo University, Tokyo, Japan

2 Fujita Health Univesity, Toyoake, Japan

3 National Cancer Center, Tokyo, Japan

4 St. Luke’s International Hospital Affiliated Clinic, Tokyo, Japan

5 Hyogo Prefecture University, Akashi, Japan

6 Miyagi Cancer Association, Sendai, Japan

7 National Health Institute, Wako, Japan

Summary

AI Generated

A systematic review and network meta-analysis of 17 randomized controlled trials found that total colonoscopy screening had significantly lower participation rates but higher single-round detection rates for advanced neoplasia and colorectal cancer compared to fecal immunochemical testing, though cumulative effectiveness across screening intervals remains unclear.

Total colonoscopy screening had median participation of 21.5% compared to 50.4% for fecal immunochemical testing and 32.3% for flexible sigmoidoscopy in 341,123 screening invitees across 17 trials
Single-round advanced neoplasia detection was significantly higher for total colonoscopy versus fecal immunochemical testing (RR=2.18, 95%CI:1.46-3.26) and colorectal cancer detection was also higher (RR=1.80, 95%CI:1.04-3.12)
A quasi-experimental study with extended follow-up found cumulative detection rates after four rounds of fecal immunochemical testing (advanced neoplasia 4.5%, colorectal cancer 0.5%) were higher than one-time colonoscopy (2.2% and 0.2% respectively)
The authors conclude that single-round colonoscopy performance may be superior but cumulative effectiveness comparisons accounting for different screening intervals (two years for fecal immunochemical testing, ten years for colonoscopy) are needed
This review is relevant for policymakers and gastroenterologists evaluating colorectal cancer screening strategies and interpreting ongoing randomized controlled trials of colonoscopy screening

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Abstract

Introduction

The modality for colorectal cancer (CRC) screening has transferred from guaiac fecal occult blood testing (gFOBT) to fecal immunochemical testing (FIT), but its sensitivity remains lower. While total colonoscopy (TCS) has been anticipated as a new modality for CRC screening, conclusive results based on randomized controlled trials (RCTs) are still pending. Test performance RCTs have been utilized to predict the effectiveness of new modalities for CRC screening. They were adopted for the evaluation of cancer screening using a stepwise approach in the World Endoscopic Evaluation (Young et al. Cancer 2016).

Aims & Methods

A systematic review of test performance RCTs for CRC screening was conducted. Candidate articles were searched from inception to October 14, 2023, using Ovid MEDLINE, Cochrane Central Registry, Embase, and Ichushi-web. We compared the test performance of TCS screening, referring to the following modalities: gFOBT, FIT, flexible sigmoidoscopy (FS), and CT colonography (CTC). Single and multiple rounds were searched. Test performance indicators included participation rates in CRC screening, advanced neoplasia (AN) detection rates, and CRC detection rates. The primary results were evaluated using an intention-to-screen (ITS) based network meta-analysis, and a per-protocol analysis was also performed.

Results

Seventeen RCTs (13 from Europe, two from the US, and one each from Israel and China), involving a total of 341,123 healthy screening invitees, were included. The median participation rates for the programs based on FIT, FS, and TCS were 50.4 % (28.6-94.0%), 32.3% (7.9-52.1%), and 21.5% (10.0-42.5%), respectively. In the network meta-analysis, participation rates for TCS screening were significantly lower than the programs based on FS (RR=0.58; CI: 0.37-0.89), FIT (RR=0.45; CI: 0.31-0.65), and gFOBT (RR=0.45; CI: 0.30-0.69). Detection rates for AN were consistently higher for TCS than for FIT (RR= 2.18, 95%CI:1.46-3.26) but not statistically significant for FS (RR=1.06, 95CI: 0.65-1.73). Similarly, TCS had higher CRC detection rates compared to FIT (RR= 1.80, 95%CI:1.04-3.12) and FS (RR= 1.52, 95%CI:0.87-2.64). While AN and CRC detection rates for TCS were higher than those of CTC, the differences were not statistically significant (AN: RR= 1.02, 95%CI:0.65-1.73, CRC: RR= 0.73 95%CI: 0.32-1.64). The follow-up period of single-round RCTs was limited until diagnosis, but the screening frequency varied depending on the follow-up duration, which could affect effectiveness. Screening intervals were typically two years for FIT, five years for FS, and ten years for CS. One quasi-experimental study combined the following arms from different RCTs with extended follow-up: one-time CS, one-time FS, and four rounds of FIT (Grobbee et al. Clin Gastroenterol Hepatol 2020). The participation rate was higher for FIT (73%) compared to FS (31%) and CS (24%). Cumulative AN and CRC detection rates were higher for FIT (AN = 4.5%, 95%CI:4.2-4.9, CRC =0.5% 95%CI: 0.4–0.6), but nearly equivalent for CS (AN = 2.2%, 95%CI:1.8-2.6, CRC =0.2% 95%CI: 0.1–0.3) and FS (AN = 2.3%, 95%CI:2.0-2.7, CRC =0.2% 95%CI: 0.1–0.3).

Conclusion

The single-round test performance of colonoscopy screening might be superior to that of other modalities. To confirm the priority of TCS, it is insufficient to draw conclusions based on the results of a single-round performance, given variations in screening intervals and frequencies among other modalities. Cumulative effects among different modalities should be compared within the same follow-up period.

References

Young GP, Senore C, Mandel JS, et al. Recommendations for a step-wise comparative approach to the evaluation of new screening tests for colorectal cancer. Cancer. 2016;122(6):826-39.

Grobbee EJ, van der Vlugt M, van Vuuren AJ, et al. Diagnostic yield of one-time colonoscopy vs one-time flexible sigmoidoscopy vs multiple rounds of mailed fecal immunohistochemical tests in colorectal cancer screening. Clin Gastroenterol Hepatol. 2020;18(3):667-75.

Conference

UEG Week Vienna 2024

Topics

Colorectal

Submission format

Abstract

Session

LOWER GI (Posters)

Citation

United European Gastroenterology Journal 2024; 12 (Supplement 8)

Published

2024

More Like This:

Challenges and strategies to bring microbiome into clinical practice

Gianluca Ianiro

BIOPSY-BASED SINGLE-CELL PROFILING OF ULCERATIVE COLITIS AND CROHN’S DISEASE REVEALS SHARED INFLAMMATORY ARCHITECTURE AND DISEASE-SPECIFIC IMMUNE PATHWAYS

Klaas Nico Faber

A SPATIALLY ORGANIZED IMMUNE-STROMAL PROGRAM DRIVES THE FISSURE-TO-FISTULA CONTINUUM IN CROHN’S DISEASE

Federica Ungaro

TISSUE FOLDS ORGANISE COLON LYMPHATICS TO CHANNEL INTERSTITIAL OUTFLOW AND PROMOTE RESILIENCE AGAINST INFLAMMATORY SWELLING

Rafael Czepielewski

MARKERS OF ECM REMODELING AND WOUND HEALING ARE ASSOCIATED WITH FIBROSTENOTIC CROHN DISEASE

Florian Rieder

Predicting outcomes based on B-cell profiles

Arno R. Bourgonje

UEG Presentation

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Challenges and strategies to bring microbiome into clinical practice

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Challenges and strategies to bring microbiome into clinical practice

Gianluca Ianiro 1

Affiliations

1 Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Catholic University of Rome, Rome, Italy

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Abstract

Event

UEG Week Barcelona 2026

Topics

Mechanisms & Personalised Medicine Gut Microbiota

Session

Innovations in gut microbiota diagnostics and therapeutics

Citation

2026: United European Gastroenterology Journal 2026; 14 (S1)

Published

2026

More Like This:

Challenges and strategies to bring microbiome into clinical practice

Gianluca Ianiro

BIOPSY-BASED SINGLE-CELL PROFILING OF ULCERATIVE COLITIS AND CROHN’S DISEASE REVEALS SHARED INFLAMMATORY ARCHITECTURE AND DISEASE-SPECIFIC IMMUNE PATHWAYS

Klaas Nico Faber

A SPATIALLY ORGANIZED IMMUNE-STROMAL PROGRAM DRIVES THE FISSURE-TO-FISTULA CONTINUUM IN CROHN’S DISEASE

Federica Ungaro

TISSUE FOLDS ORGANISE COLON LYMPHATICS TO CHANNEL INTERSTITIAL OUTFLOW AND PROMOTE RESILIENCE AGAINST INFLAMMATORY SWELLING

Rafael Czepielewski

MARKERS OF ECM REMODELING AND WOUND HEALING ARE ASSOCIATED WITH FIBROSTENOTIC CROHN DISEASE

Florian Rieder

Predicting outcomes based on B-cell profiles

Arno R. Bourgonje

UEG Presentation

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BIOPSY-BASED SINGLE-CELL PROFILING OF ULCERATIVE COLITIS AND CROHN’S DISEASE REVEALS SHARED INFLAMMATORY ARCHITECTURE AND DISEASE-SPECIFIC IMMUNE PATHWAYS

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BIOPSY-BASED SINGLE-CELL PROFILING OF ULCERATIVE COLITIS AND CROHN’S DISEASE REVEALS SHARED INFLAMMATORY ARCHITECTURE AND DISEASE-SPECIFIC IMMUNE PATHWAYS

E.A.M. (Noortje) Festen 1, Paola Pibiri 2, Roy Oelen 2, Werna T. C. Uniken Venema 3, Emilia Bigaeva 1, Monique G.P. Van der Wijst 2, Maria Paraskevopoulou 4, Klaas Nico Faber 2

Affiliations

1 UMCG, Groningen, Netherlands

2 University Medical Center Groningen, Groningen, Netherlands

3 Zuyderland Medisch Centrum, Leuven, Belgium

4 Takeda Pharmaceuticals, Acton, United States

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Abstract

Introduction

Ulcerative colitis (UC) and Crohn’s disease (CD) share chronic intestinal inflammation but differ in clinical behavior and treatment response. Although single-cell RNA sequencing (scRNA-seq) studies have advanced understanding of IBD biology, limited sample sizes have hindered robust comparison of shared versus disease-specific mechanisms. We therefore performed a large-scale meta-analysis of gut mucosal scRNA-seq datasets to define common inflammatory architecture and divergent immune programs in UC and CD.

Aims & Methods

Gut mucosal scRNA-seq datasets from two CD and two UC cohorts were integrated using a standardized computational workflow for preprocessing, harmonization, and downstream analysis. Cell-type annotation, differential abundance and gene expression analyses, pathway enrichment, and cell–cell communication inference were performed to compare inflamed and non-inflamed tissue within each disease and identify shared versus disease-specific programs.

Results

We generated disease-specific atlases comprising more than 405,000 cells from approximately 190 patients with CD and 313,000 cells from approximately 72 patients with UC. Across both diseases, inflammation followed a shared remodeling program marked by epithelial cell loss, expansion of immune populations, and activation of immune-related pathways. Despite this common inflammatory framework, immune execution diverged by disease. In CD, CD8+ T cells declined in inflamed tissue, whereas in UC they expanded together with other immune subsets. B cells showed a similar contrast, with enrichment of innate and stress-response pathways in CD versus adaptive and humoral immune programs in UC. Monocytes added further specificity, with strong enrichment of JAK-STAT signaling observed only in UC. Consistently, cell-cell communication analysis indicated stronger adaptive immune interactions in UC than in CD.

Conclusion

UC and CD share a common inflammation-associated tissue remodeling program, but diverge in the immune pathways and cellular interactions that dominate the inflamed mucosa. These findings provide a systems-level framework for understanding IBD heterogeneity and may help prioritize phenotype-specific therapeutic targets.

References

1. Martin, J. C. et al. Single-Cell Analysis of Crohn’s Disease Lesions Identifies a Pathogenic Cellular Module Associated with Resistance to Anti-TNF Therapy. Cell 178, 1493-1508.e20 (2019).
2. Smillie, C. S. et al. Intra- and Inter-cellular Rewiring of the Human Colon during Ulcerative Colitis. Cell 178, 714-730.e22 (2019).
3. Jaeger, N. et al. Single-cell analyses of Crohn’s disease tissues reveal intestinal intraepithelial T cells heterogeneity and altered subset distributions. Nat. Commun. 12, 1921 (2021).
4. Calviño-Suárez, C. et al. Exploration of JAK/STAT pathway activation in ulcerative colitis reveals sex-dependent activation of JAK2/STAT3 in the inflammatory response. Front. Immunol. 16, 1609740 (2025).

Event

UEG Week Barcelona 2026

Topics

Gut Microbiota Mechanisms & Personalised Medicine Immunology IBD

Submission format

Abstract

Session

New insights into IBD mechanisms

Citation

2026: United European Gastroenterology Journal 2026; 14 (S1)

Published

2026

More Like This:

Challenges and strategies to bring microbiome into clinical practice

Gianluca Ianiro

BIOPSY-BASED SINGLE-CELL PROFILING OF ULCERATIVE COLITIS AND CROHN’S DISEASE REVEALS SHARED INFLAMMATORY ARCHITECTURE AND DISEASE-SPECIFIC IMMUNE PATHWAYS

Klaas Nico Faber

A SPATIALLY ORGANIZED IMMUNE-STROMAL PROGRAM DRIVES THE FISSURE-TO-FISTULA CONTINUUM IN CROHN’S DISEASE

Federica Ungaro

TISSUE FOLDS ORGANISE COLON LYMPHATICS TO CHANNEL INTERSTITIAL OUTFLOW AND PROMOTE RESILIENCE AGAINST INFLAMMATORY SWELLING

Rafael Czepielewski

MARKERS OF ECM REMODELING AND WOUND HEALING ARE ASSOCIATED WITH FIBROSTENOTIC CROHN DISEASE

Florian Rieder

Predicting outcomes based on B-cell profiles

Arno R. Bourgonje

UEG Presentation

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A SPATIALLY ORGANIZED IMMUNE-STROMAL PROGRAM DRIVES THE FISSURE-TO-FISTULA CONTINUUM IN CROHN’S DISEASE

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A SPATIALLY ORGANIZED IMMUNE-STROMAL PROGRAM DRIVES THE FISSURE-TO-FISTULA CONTINUUM IN CROHN’S DISEASE

Luca Massimino 1, Sabrina Nicolo' 1, Tommaso Lorenzo Parigi 1, Sara Mino 2, Mattia Bugatti 2, Francesca Nicola 1, Nicola Ivan Lorè 1, Vincenzo Villanacci 2, Paola Parente 3, Fabrizio Bossa 4, Orazio Palmieri 5, Pierpaolo Sileri 1, Silvio Danese 6, Federica Ungaro 1

Affiliations

1 Ospedale San Raffaele, Milano, Italy

2 Institute of Pathology, ASST Spedali Civili and University of Brescia, Brescia, Italy

3 Pathology Unit, Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy

4 Fondazione Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy

5 Division of Gastroenterology, Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy

6 Vita-Salute San Raffaele University - IRCCS San Raffaele Scientific Institute, Milan, Italy

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Abstract

Introduction

Fistulizing Crohn’s disease represents a severe and disabling complication characterized by transmural inflammation and aberrant tissue remodeling. Although fissures are considered precursors of fistulas, the cellular and molecular mechanisms driving this transition remain poorly defined. We aimed to characterize the spatial immune-stromal interactions underlying fissure formation and progression toward fistula.

Aims & Methods

Spatial transcriptomics was performed on intestinal surgical specimens from Crohn’s disease patients with inflamed tissue, increasing-depth fissures, and entero-enteric fistulas. Spatial data were integrated with single-cell reference datasets and pseudotime analysis to reconstruct stromal and myeloid differentiation trajectories and were utilized to identify ligand-receptor signaling networks across defined tissue compartments.

Results

Fissure-associated regions were enriched in inflammatory fibroblasts and inflammatory monocytes, identifying fissures as active immune-stromal niches rather than passive structural defects. Pseudotime reconstruction revealed coordinated differentiation programs in which stromal cells and myofibroblasts transitioned into inflammatory fibroblasts, while inflammatory monocytes differentiated into macrophages and LAMP3⁺ dendritic cells. Ligand-receptor analysis demonstrated a progressive shift from early chemokine-mediated recruitment dominated by CXCL12-CXCR4 signaling to adhesion- and retention-mediated circuits involving Complement, ADGRE5-CD55, and THY1-integrin pathways. These changes established a spatially confined and self-sustaining immune-stromal microenvironment in advanced fissures and fistulas.

Conclusion

Fissures represent active immune-stromal niches that initiate and sustain cellular and molecular programs driving fistula formation. The transition from chemokine-driven recruitment to adhesion-mediated immune retention defines a key mechanistic step in fistulization. These findings identify early fissures as a potential therapeutic window and highlight CXCR4, Complement, and immune-stromal adhesion pathways as candidate targets to prevent fistula development in Crohn’s disease.

Event

UEG Week Barcelona 2026

Topics

Mechanisms & Personalised Medicine Immunology IBD

Submission format

Abstract

Session

Immunologic pathways of disease and drug response in IBD

Citation

2026: United European Gastroenterology Journal 2026; 14 (S1)

Published

2026

More Like This:

Challenges and strategies to bring microbiome into clinical practice

Gianluca Ianiro

BIOPSY-BASED SINGLE-CELL PROFILING OF ULCERATIVE COLITIS AND CROHN’S DISEASE REVEALS SHARED INFLAMMATORY ARCHITECTURE AND DISEASE-SPECIFIC IMMUNE PATHWAYS

Klaas Nico Faber

A SPATIALLY ORGANIZED IMMUNE-STROMAL PROGRAM DRIVES THE FISSURE-TO-FISTULA CONTINUUM IN CROHN’S DISEASE

Federica Ungaro

TISSUE FOLDS ORGANISE COLON LYMPHATICS TO CHANNEL INTERSTITIAL OUTFLOW AND PROMOTE RESILIENCE AGAINST INFLAMMATORY SWELLING

Rafael Czepielewski

MARKERS OF ECM REMODELING AND WOUND HEALING ARE ASSOCIATED WITH FIBROSTENOTIC CROHN DISEASE

Florian Rieder

Predicting outcomes based on B-cell profiles

Arno R. Bourgonje

UEG Presentation

New

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TISSUE FOLDS ORGANISE COLON LYMPHATICS TO CHANNEL INTERSTITIAL OUTFLOW AND PROMOTE RESILIENCE AGAINST INFLAMMATORY SWELLING

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TISSUE FOLDS ORGANISE COLON LYMPHATICS TO CHANNEL INTERSTITIAL OUTFLOW AND PROMOTE RESILIENCE AGAINST INFLAMMATORY SWELLING

Rahul Ravindran 1, Drishya Iyer 2, Daniel Lee 2, Meghan Blitchington 3, Christopher Huckstep 2, Riley Telkamp 3, Kevin Telfer 2, Lillian O'Neal 3, Rachel Mintz 2, Deanna Davis 2, Kibeom Park 2, Nadav Yayon 1, Shashi Kumar 2, Alexandre Gallerand 2, Ahmed Hedayat 2, Changqing Ma 2, Mark Hoofnagle 2, Raphael Blain 4, Adrien Hallou 4, Young-Kwon Hong 5, Simon Travis 4, Matthias Friedrich 4, Huaibin Ko 6, Ryan C. Ungaro 6, Chao Zhou 2, Jean-Frédéric Colombel 6, Fiona Powrie 4, Mark Coles 4, Christopher Buckley 4, Bernd Zinselmeyer 2, Gwendalyn Randolph 2, Rafael Czepielewski 3

Affiliations

1 University of Cambridge, Cambridge, United Kingdom

2 Washington University in St. Louis, Saint Louis, United States

3 Augusta University, Augusta, United States

4 University of Oxford, Oxford, United Kingdom

5 Harvard Medical School, Boston, United States

6 Icahn School of Medicine at Mount Sinai, New York City, United States

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Abstract

Introduction

The lymphatic vasculature is essential for tissue homeostasis, yet the organisation and function of colonic lymphatics remain poorly defined compared with those of the small intestine. In particular, how lymphatic vessels integrate with the structural landscape of the colon to regulate interstitial fluid drainage and immune organisation is not well understood.

Aims & Methods

This study aimed to define the anatomical organisation of colonic lymphatic vessels and determine how tissue architecture influences interstitial fluid drainage and immune positioning. Using whole-organ imaging, we examined the spatial development and distribution of colonic initial lymphatic vessels. To assess drainage pathways, exogenous and endogenous tracers were tracked through the colonic interstitium. The spatial relationships among lymphatic vessels, blood vessels, macrophages, and lymphoid tissue were also analysed. Finally, tissue architecture was examined under inflammatory conditions using human ulcerative colitis samples and a DSS-induced colitis mouse model.

Results

Colonic initial lymphatic vessels developed postnatally and were positioned beneath epithelial crypts. These crypts were embedded within a pre-existing macroscopic tissue landscape characterised by tent-like folds, which created prominent interstitial pockets beneath them. Tracer tracking revealed that interstitial fluid outflow was not uniform but instead followed geometry-dependent drainage pathways defined by these folds. Colon folds spatially coordinated lymphatic vessels, blood vessels, macrophages, and lymphoid tissue, forming integrated stromal-vascular-immune reservoirs positioned to receive and concentrate interstitial cargo. In inflammatory conditions, human ulcerative colitis tissue showed focal loss of folds at sharp boundaries between inflamed and adjacent healthy regions. Consistently, during DSS-induced colitis, folds widened in an accordion-like manner over an expanding submucosa, indicating that fold geometry dynamically adapts under inflammatory stress.

Conclusion

These findings identify colon folds as anatomical scaffolds that organise lymphatic, vascular, and immune components to create specialised drainage routes within the tissue. Tissue geometry therefore emerges as a major organiser of colonic drainage architecture. Disruption of this structural framework during inflammation may compromise interstitial drainage and immune positioning.

References

Czepielewski, R. S. et al. Ileitis-associated tertiary lymphoid organs arise at lymphatic valves and impede mesenteric lymph flow in response to tumor necrosis factor. Immunity 54, 2795-2811 e2799 (2021).
Nava, G. M., Friedrichsen, H. J. & Stappenbeck, T. S. Spatial organization of intestinal microbiota in the mouse ascending colon. ISME J 5, 627-638 (2011).
Randolph, G. J., Ivanov, S., Zinselmeyer, B. H. & Scallan, J. P. The Lymphatic System: Integral Roles in Immunity. Annual Review of Immunology 35, 31-52 (2017).
Uzzan, M. et al. Ulcerative colitis is characterized by a plasmablast-skewed humoral response associated with disease activity. Nat Med 28, 766-779 (2022).

Event

UEG Week Barcelona 2026

Topics

Gut Microbiota Mechanisms & Personalised Medicine Immunology IBD

Submission format

Abstract

Session

New insights into IBD mechanisms

Citation

2026: United European Gastroenterology Journal 2026; 14 (S1)

Published

2026

More Like This:

Challenges and strategies to bring microbiome into clinical practice

Gianluca Ianiro

BIOPSY-BASED SINGLE-CELL PROFILING OF ULCERATIVE COLITIS AND CROHN’S DISEASE REVEALS SHARED INFLAMMATORY ARCHITECTURE AND DISEASE-SPECIFIC IMMUNE PATHWAYS

Klaas Nico Faber

A SPATIALLY ORGANIZED IMMUNE-STROMAL PROGRAM DRIVES THE FISSURE-TO-FISTULA CONTINUUM IN CROHN’S DISEASE

Federica Ungaro

TISSUE FOLDS ORGANISE COLON LYMPHATICS TO CHANNEL INTERSTITIAL OUTFLOW AND PROMOTE RESILIENCE AGAINST INFLAMMATORY SWELLING

Rafael Czepielewski

MARKERS OF ECM REMODELING AND WOUND HEALING ARE ASSOCIATED WITH FIBROSTENOTIC CROHN DISEASE

Florian Rieder

Predicting outcomes based on B-cell profiles

Arno R. Bourgonje

UEG Poster

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MARKERS OF ECM REMODELING AND WOUND HEALING ARE ASSOCIATED WITH FIBROSTENOTIC CROHN DISEASE

Letizia Satriano 1, Lucie Auffret 2, Marta Sorokina Alexdóttir 1, Thomai Tsapanou-Katranara 1, Catherine Larsen 2, Soha Razmjouei 2, Samantha Gauriloff 2, Anne-Christine Bay-Jensen 1, Morten Asser Karsdal 1, Joachim Høg Mortensen 1, Florian Rieder 2

Affiliations

1 Nordic Bioscience A/S, Herlev, Denmark

2 Cleveland Clinic Research, Cleveland Clinic, Ohio, United States

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Abstract

Introduction

Crohn’s disease (CD) is a chronic inflammatory condition of the gastrointestinal tract, characterized by excessive extracellular matrix (ECM) remodeling that leads to fibrosis and stricture formation. Strictures are primarily detected using imaging techniques, such as computed tomography and magnetic resonance imaging. However, no validated biomarkers are currently available to assess the presence of strictures. The discovery of such biomarkers would improve early diagnosis and facilitate more effective patient management using anti-fibrotic and anti-inflammatory treatments.

Aims & Methods

In the current study, we aimed to investigate the association of biomarkers reflecting ECM remodeling, fibroblast activity, and neutrophil activity with CD phenotypes. The cohort included 41 controls (CTR) without a family history of CD or resections and 129 CD patients divided into four phenotypes: stricture (S) (n=41), inflammation no stricture (I) (n=32), no active inflammation no stricture (NI) (n=46), and stricture with penetrating disease (S/IP) (n=10). Serum markers of collagen type VI formation (PRO-C6), type III and type VII degradation (C3M, C7M), and a human neutrophil elastase-derived fragment of calprotectin (CPa9-HNE) were measured via ELISA. Patients were grouped based on phenotypes, and biomarkers were evaluated by one-way ANOVA, correcting for multiple comparisons using Dunn’s test. For two-group comparisons, Mann-Whitney test was applied. Correlations were assessed with the Spearman method. The global stricture score includes both inflammatory and non-inflammatory components.

Results

C3M, CPa9-HNE, and PRO-C6 showed moderate to significant elevation in CD compared to CTR (C3M: p=0.01; CPa9-HNE: p=0.05; PRO-C6: p=0.07). In patients with CD, PRO-C6 was higher in stricturing than in non-inflamed CD (p=0.04), and CPa9-HNE, C7M, and C3M/PRO-C3 were higher in stricture with penetrating CD than in non-inflamed CD (CPa9-HNE: p =0.02, C7M: p =0.02, C3M/PRO-C3: p =0.009). Levels of CPa9-HNE, C3M, and C7M positively correlated with global stricture severity score, and along with PRO-C6, differed moderately to significantly between the upper and lower quartiles of this score (CPa9-HNE: p=0.03, C3M: p=0.03, C7M: p=0.001, PRO-C6: p =0.06).

Conclusion

The fibrosis marker (PRO-C6) was associated with stenosis and was elevated in CD patients with high levels of global stricture scores. Markers of mucosal damage (C7M, C3M/PROC3) and inflammation (CPa9-HNE) were associated with patients with stenosis and penetrating disease and showed a positive association with the global stricture score. These data suggest that markers of ECM remodeling could be valuable tools for assessing fibrostenosis in CD patients.

Conference

UEG Week Barcelona 2026

Topics

IBD

Submission format

Abstract

Session

Fibrosis in IBD (Posters)

Citation

2026: United European Gastroenterology Journal 2026; 14 (S1)

Published

2026

More Like This:

Challenges and strategies to bring microbiome into clinical practice

Gianluca Ianiro

BIOPSY-BASED SINGLE-CELL PROFILING OF ULCERATIVE COLITIS AND CROHN’S DISEASE REVEALS SHARED INFLAMMATORY ARCHITECTURE AND DISEASE-SPECIFIC IMMUNE PATHWAYS

Klaas Nico Faber

A SPATIALLY ORGANIZED IMMUNE-STROMAL PROGRAM DRIVES THE FISSURE-TO-FISTULA CONTINUUM IN CROHN’S DISEASE

Federica Ungaro

TISSUE FOLDS ORGANISE COLON LYMPHATICS TO CHANNEL INTERSTITIAL OUTFLOW AND PROMOTE RESILIENCE AGAINST INFLAMMATORY SWELLING

Rafael Czepielewski

MARKERS OF ECM REMODELING AND WOUND HEALING ARE ASSOCIATED WITH FIBROSTENOTIC CROHN DISEASE

Florian Rieder

Predicting outcomes based on B-cell profiles

Arno R. Bourgonje

UEG Presentation

New

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Predicting outcomes based on B-cell profiles

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Predicting outcomes based on B-cell profiles

Arno R. Bourgonje 1

Affiliations

1 University Medical Center of Groningen, Groningen, Netherlands

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Abstract

Event

UEG Week Barcelona 2026

Topics

Immunology Mechanisms & Personalised Medicine IBD

Session

Disease primer: Unexpected cellular players in IBD

Citation

2026: United European Gastroenterology Journal 2026; 14 (S1)

Published

2026

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Predicting outcomes based on B-cell profiles

Arno R. Bourgonje