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TRANSMURAL CROSS-SECTIONAL FINDINGS AND BOWEL DAMAGE ASSESSMENT IN PRECLINICAL CROHN’S DISEASE: A CASE-CONTROL STUDY

Iago Rodríguez-Lago 1, Marta Aduna 2, Patricia Ramírez de la Piscina Urraca 3, Olga Merino 4, Juan Carrascosa Gil 5, REBECA HIGUERA 6, Ainara Maíz 7, Eva Zapata 8, Jose Luis Cabriada Nuño 1, Manuel Barreiro de Acosta 9

Affiliations

1 Hospital Universitario de Galdakao, Bilbao, Spain

2 OSATEK, Galdakao, Spain

3 Hospital Universitario Araba, Vitoria, Spain

4 Hospital Universitario de Cruces, Barakaldo, Spain

5 Hospital de Zumárraga, Zumárraga, Spain

6 Hospital San Eloy, Barakaldo, Spain

7 Hospital Universitario Donostia, Donostia, Spain

8 Hospital de Mendaro, Mendaro, Spain

9 Hospital Clínico Universitario de Santiago, Santiago de Compostela, Spain

Summary

AI Generated

Asymptomatic patients with preclinical Crohn's disease detected during colorectal cancer screening show similar MRI findings and bowel damage to patients with new-onset symptomatic disease.

In 19 preclinical CD patients compared to 19 matched symptomatic controls, the Lémann Index showed no significant difference overall (p=0.95), though preclinical cases had higher colonic/rectum scores (p=0.014)
The most frequent MRI findings in preclinical CD were contrast enhancement and wall thickening (79% each), oedema (42%), lymphadenopathy (68%), and increased vascularity (42%)
Among patients with strictures, symptomatic controls showed higher rates of preestenotic dilation (100% vs 0%, p=0.01) than preclinical cases
Preclinical CD patients who subsequently developed symptoms showed no difference in Lémann Index compared to those who remained asymptomatic (median 1.0 vs 1.1, p=0.71)
The authors recommend close monitoring of asymptomatic patients with incidental CD findings based on the similar degree of bowel damage observed

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Abstract

Introduction

Crohn’s disease (CD) is a chronic inflammatory condition that leads to cumulative structural bowel damage. The Lémann Index is a validated tool that can be a useful for monitoring the progression of the disease and evaluating the effectiveness of different therapies. Recent data have shown a range of biomarkers and endoscopic findings preceding the diagnosis of CD.

Aims & Methods

Our aim was to describe the most frequent cross-sectional findings in asymptomatic patients with an incidental diagnosis of CD and to evaluate the progression of bowel damage from a preclinical stage until the symptomatic onset of the disease. Patients with an incidental diagnosis of CD during the colorectal cancer screening programme were included. Only patients with available MRI enterography were included. They were compared 1:1 to controls matched by disease extent from an inception cohort of patients with CD diagnosed after symptomatic onset of the disease. All cross-sectional examinations were centrally-read by one experienced radiologist, performing a descriptive analysis of the main radiological findings and calculation of Lémann score on both cohorts. Descriptive statistics were used along with comparisons with chi-square tests and Mann-Whitney analysis.

Results

A total of 38 patients were included: 19 cases with preclinical CD and 19 matched-controls (age 55 years (IQR, 54-62) vs 49 years (IQR, 45-58); 53% vs 42% male; 74% vs 53% non-smokers, respectively). CD location was 53% L1, 21% L2 and 26% L3; and CD behaviour was B1 in 74% vs 79%; B2 in 26% vs 16%; and none vs 5%, among cases and controls, respectively.
The most frequent transmural findings on MRI were contrast enhancement and wall thickening (79% respectively), followed by oedema (42%), while among extraintestinal findings they were lymphadenopathy (68%) and increased vascularity (42%). Among patients with strictures, controls showed a higher rate of preestenotic dilation (100% vs 0%, p=0.01).
Bowel damage assessment revealed no statistically significant differences in the Lémann index between preclinical CD and controls (p=0.95). However, we observed that cases had statistically significant higher scores in the colonic/rectum score (p=0.014). We found no differences in the Lémann index between preclinical CD patients who subsenquently developed symptoms (median LI 1.0 [IQR, 0.3-2.0]) and those who did not (1.1 [IQR, 0.68-2.65], respectively, p=0.71) or with controls (1.3 [IQR, 0.0-3.1], respectively, p=0.96).

Conclusion

Patients with preclinical CD demonstrate similar findings on MRI enterography and they have the same degree of bowel damage as new-onset symptomatic CD. Close monitoring should be recommended based on these findings.

Conference

UEG Week Copenhagen 2023

Topics

IBD

Submission format

Abstract

Session

PP 05 IBD (Posters)

Citation

United European Gastroenterology Journal 2023; 11 (Supplement 8)

Published

2023

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Introduction: Chronic constipation: How to diagnose and treat this frequent condition in clinical practice

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Introduction: Chronic constipation: How to diagnose and treat this frequent condition in clinical practice

Maura Corsetti 1

Affiliations

1 University of Nottingham, Nottingham, United Kingdom

Summary

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Abstract

Event

Postgraduate Teaching Programme Barcelona 2026

Topics

Neurogastroenterology & Motility Surgery Primary Care Small Intestine & Nutrition

Session

Chronic constipation: How to diagnose and treat this frequent condition in clinical practice

Citation

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

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When is the time to call the surgeon?

Emma V. Carrington 1

Affiliations

1 University of North Carolina / NCRBSI, London, United Kingdom

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Abstract

Event

Postgraduate Teaching Programme Barcelona 2026

Topics

Neurogastroenterology & Motility Surgery Primary Care Small Intestine & Nutrition

Session

Chronic constipation: How to diagnose and treat this frequent condition in clinical practice

Citation

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

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2026

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UEG Presentation

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Clinical scenario 1: What’s the problem? Give a laxative and it’s sorted

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Clinical scenario 1: What’s the problem? Give a laxative and it’s sorted

Christian Lambiase 1

Affiliations

1 Gastrointestinal Unit, Department of Translational Sciences and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy

Summary

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Abstract

Event

Postgraduate Teaching Programme Barcelona 2026

Topics

Neurogastroenterology & Motility Surgery Primary Care Small Intestine & Nutrition

Session

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Citation

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

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2026

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UEG Presentation

New

Share via Email Share on Facebook Share on X Share on LinkedIn Share on Bluesky

Summary: Chronic constipation: How to diagnose and treat this frequent condition in clinical practice

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Summary: Chronic constipation: How to diagnose and treat this frequent condition in clinical practice

Allison Malcolm 1

Affiliations

1 University Of Sydney, Sydney, Australia

Summary

AI Generated

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Abstract

Event

Postgraduate Teaching Programme Barcelona 2026

Topics

Neurogastroenterology & Motility Surgery Primary Care Small Intestine & Nutrition

Session

Chronic constipation: How to diagnose and treat this frequent condition in clinical practice

Citation

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

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2026

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UEG Podcast Episode

Journal Podcast

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Angiotensin receptor blockers: its influence in patients on a gluten-free diet

Iago Rodríguez-Lago 1, Neil O'Morain 2

Affiliations

1 Hospital Universitario de Galdakao, Bilbao, Spain

2 Institut Arnault Tzanck, Saint-Laurent-du-Var, France

Summary

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Abstract

Topics

Neurogastroenterology & Motility

Published

2021

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Christian Lambiase

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THE EXTRACELLULAR MATRIX PROTEIN EMILIN-1 IMPACTS ON THE MICROENVIRONMENT BY HAMPERING THE DEVELOPMENT AND PROGRESSION OF GASTRIC CANCER

Alessandra Capuano 1, Maddalena Vescovo 1, Eugenio Scanziani 2, Samanta Muzzin 1, Sachiyo Nomura 3, Simone Canesi 2, Stefano Realdon 1, Stefania Maiero 1, Maria Grazia Nadin 1, Irma Valeria Albergati 4, Antonino Piruzza 4, Saveria, Lory croce' 4, Renato Cannizzaro 4,1, Paola Spessotto 1

Affiliations

1 Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Aviano, Italy

2 University of Milan, Milan, Italy

3 University of Tokyo, Tokyo, Japan

4 University of Trieste, Trieste, Italy

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Abstract

Introduction

The contribution of the tumor microenvironment and extracellular matrix to the aggressive biology of Gastric Cancer (GC) has been recently characterized (1). During GC progression striking changes in the lymphatic vessels (LVs) occur and lymphatic metastasis is the commonest feature of GC spread, representing the most significant prognostic factor determining the clinical outcomes (2). Recent evidence supporting a functional link among EMILIN-1, an Extra Cellular Matrix component (ECM), tumour growth and lymph-angiogenesis has been provided. EMILIN-1 represents a key structural element in the maintenance and function of LVs and displays anti-proliferative effects through the interaction with α4β1 integrin, as demonstrated in skin and colon cancer (3,4,5). Interestingly, α4 integrin is transcriptionally repressed in GC, but not in the normal gastric epithelium (7), suggesting a crucial mechanism exerted by the integrin/EMILIN1 recognition also in this context.

Aims & Methods

The aim of this study is to analyze the possible role of EMILIN-1 as a molecular regulator in in the context of GC development and progression.
We performed Immunofluorescence staining of human gastric biopsy samples from normal and neoplastic tissues collected during the endoscopy procedures. Biopsies from pre-malignant lesions were also included. For in vivo experiments, we used the syngeneic YTN16 gastric cancer cell line (7) which was injected subcutaneously and intraperitoneally in genetically modified EMILIN-1 mice. In alternative, carcinogenesis was induced in mice using N-methyl-N-nitrosourea (MNU). GES-1 (normal stomach mucosa), and several GC cell lines representative of different GC stages and histotypes (i.e. AGS, Hs746.T, NCI-N87 and KATO-III) were employed for in vitro experiments.

Results

EMILIN-1 is diffusely deposited in normal gastric mucosa and is significantly decreased in malignant and pre-neoplastic samples; this finding correlates with the presence of aberrant LVs. EMILIN-1 mutant mice (knock out and E955A knock in) developed tumors earlier compared to WT animals: 20 days post-injection of YTN16 cells, tumors developed in EMILIN-1 mutant mice were larger and displayed a significant increase of lymphangiogenesis. Treatment of transgenic mice with MNU associated with an increased number of tumors, exacerbated aggressive lesions and higher levels of LV abnormalities.
To unveil the main mechanisms responsible for EMILIN-1 reduction we treated in vitro fibroblasts and LECs (the major cellular sources of EMILIN1 in the gastric microenvironment) with conditioned media derived from GC cells lines; dramatic effects on EMILIN1 expression were observed, both at the mRNA and protein levels. Small-RNAseq analysis on culture media allowed us to identify miR125a-5p as a possible molecular regulator of EMILIN-1 levels in this context.

Conclusion

This study demonstrates for the first time that loss of EMILIN-1 in GC leads to lymphatic dysfunction and proliferative advantages that sustain tumorigenesis, and assess the use of our animal model as a valuable tool to verify the fate of GC upon loss of EMILIN-1.

References

1. Rojas A, Araya P, Gonzalez I, Morales E. Gastric Tumor Microenvironment. Adv Exp Med Biol. 2020;1226:23–35.8
2. Deng J-Y, Liang H. Clinical significance of lymph node metastasis in gastric cancer. World J Gastroenterol. 2014;20:3967–75.
3. Capuano A, Pivetta E, Sartori G, Bosisio G, Favero A, Cover E, et al.Abrogation of EMILIN1-β1 integrin interaction promotes experimental colitis and colon carcinogenesis.Matrix Biol J Int Soc Matrix Biol. 2019;83:97–115.
4. Capuano A, Pivetta E, Baldissera F, Bosisio G, Wassermann B, Bucciotti F, et al.Integrin binding site within the gC1q domain orchestrates EMILIN-1-induced lymphangiogenesis. Matrix Biol J Int Soc Matrix Biol. 2019;81:34–49.
5. Danussi C, Petrucco A, Wassermann B, Pivetta E, Modica TM, Del Bel Belluz L, et al.EMILIN1-α4/α9 integrin interaction inhibits dermal fibroblast and keratinocyte proliferation. JCell Biol. 2011;195:131–45.
6. Park J, Song S-H, Kim TY, Choi M-C, Jong H-S, Kim T-Y, et al. Aberrant methylation of integrin alpha4 gene in human gastric cancer cells.Oncogene. 2004;23:3474–80.
7. Yamamoto M, Nomura S, Hosoi A, Nagaoka K, Iino T, Yasuda T et al. Established gastric cancer cell lines transplantable into C57BL/6 mice show fibroblast growth factor receptor 4 promotion of tumor growth. Cancer Sci. 2018 May;109(5):1480-1492.

Event

UEG Week Vienna 2024

Topics

Digestive Oncology Mechanisms & Personalised Medicine Oesophagus Stomach & H. Pylori

Submission format

Abstract

Session

Upper GI basic: Reflux, gastritis and cancer

Citation

United European Gastroenterology Journal 2024; 12 (Supplement 8)

Published

2024

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