CC BY 4.0 · Endosc Int Open 2025; 13: a25032135
DOI: 10.1055/a-2503-2135
Original article

Optimizing duodenal tissue acquisition for mechanistic studies of duodenal ablation in type 2 diabetes

1   Gastroenterology and Hepatology, Amsterdam UMC, Location VUmc, Amsterdam, Netherlands (Ringgold ID: RIN1209)
,
1   Gastroenterology and Hepatology, Amsterdam UMC, Location VUmc, Amsterdam, Netherlands (Ringgold ID: RIN1209)
,
E. Andra Neefjes-Borst
2   Pathology, Amsterdam UMC Location VUmc, Amsterdam, Netherlands (Ringgold ID: RIN1209)
,
Max Nieuwdorp
3   Internal and Vascular Medicine, Amsterdam UMC Location AMC, Amsterdam, Netherlands (Ringgold ID: RIN26066)
,
1   Gastroenterology and Hepatology, Amsterdam UMC, Location VUmc, Amsterdam, Netherlands (Ringgold ID: RIN1209)
,
1   Gastroenterology and Hepatology, Amsterdam UMC, Location VUmc, Amsterdam, Netherlands (Ringgold ID: RIN1209)
› Author Affiliations
Clinical Trial: Registration number (trial ID): NCT06333093, NCT05984238, Trial registry: ClinicalTrials.gov (http://www.clinicaltrials.gov/), Type of Study: Open-label study and double-blind sham-controlled trial.

Abstract

Background and study aims

Histological analysis of regular duodenal biopsies to study morphologic changes after duodenal ablation for type 2 diabetes (T2D) and metabolic syndrome is hampered by variability in tissue orientation. We designed an optimized tissue acquisition protocol using duodenal cold snare resections to create tissue microarrays (TMAs) and to allow for single-cell RNA sequencing (scRNA-seq).

Patients and methods

The open-label DIRECT study included patients undergoing an upper gastrointestinal interventional endoscopy for non-duodenal indications. All underwent one ot two single-piece duodenal cold snare resections. Endpoints were safety, adequate histological orientation of specimen and TMA, and tissue dissociation quality for scRNA-seq. The optimized tissue acquisition protocol was validated in a duodenal ablation study, EMINENT-2.

Results

In DIRECT, nine patients were included in whom a total of 16 cold snare resections were obtained. No severe adverse events (SAEs) occurred. Eighty percent of specimens and corresponding TMAs showed optimal tissue orientation. Further improvement was achieved by reducing tissue damage during endoscopic retrieval and improving histologic evaluation by eliminating ink use and pinning the tissue on cork. High-quality tissue dissociation scores for scRNA-seq were achieved in 13 of 18 samples (72%). In EMINENT-2, 38 cold snares were obtained without SAEs, histopathologic analysis showed good orientation in all samples, and dissociation scores for scRNA-seq were qualified in 35/38 (92%) samples.

Conclusions

Duodenal cold snare resection is safe and can provide high-quality tissue for optimally oriented TMAs and high-quality tissue dissociation scores for scRNA-seq (Clinicaltrials.gov, NCT06333093, NCT05984238). This approach will allow mechanistic studies about the effects of duodenal ablation on metabolic syndrome and T2D.

Supplementary Material



Publication History

Received: 20 August 2024

Accepted after revision: 11 December 2024

Accepted Manuscript online:
16 December 2024

Article published online:
29 January 2025

© 2025. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/).

Georg Thieme Verlag KG
Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany

Bibliographical Record
Celine B.E. Busch, Kim van den Hoek, E. Andra Neefjes-Borst, Max Nieuwdorp, Annieke C.G. van Baar, Jacques J.H.G.M. Bergman. Optimizing duodenal tissue acquisition for mechanistic studies of duodenal ablation in type 2 diabetes. Endosc Int Open 2025; 13: a25032135.
DOI: 10.1055/a-2503-2135
 
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