Faecal Volatile Organic Compounds to Detect Colorectal Neoplasia in Lynch Syndrome—A Prospective Longitudinal Multicentre Study

IF 6.7 1区医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Alimentary Pharmacology & Therapeutics Pub Date : 2024-10-18 DOI:10.1111/apt.18328

Elsa L. S. A. van Liere, Dewkoemar Ramsoekh, Emma Daulton, Maya Dakkak, Joris M. van Lingen, Trenton K. Stewart, Sofie Bosch, Beatriz Carvalho, Evelien Dekker, Maarten A. J. M. Jacobs, Jan Jacob Koornstra, Johan P. Kuijvenhoven, Monique E. van Leerdam, Tim G. J. de Meij, Gerrit A. Meijer, Manon C. W. Spaander, James A. Covington, Nanne K. H. de Boer

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Abstract

Background

Non-invasive biomarkers may reduce post-colonoscopy colorectal cancer (CRC) rates and colonoscopy overuse in Lynch syndrome. Unlike faecal immunochemical test (FIT), faecal volatile organic compounds (VOCs) may accurately detect both advanced and non-advanced colorectal neoplasia.

Aim

The aim of this study was to evaluate the potential of faecal VOCs—separately and with FIT—to guide optimal colonoscopy intervals in Lynch syndrome.

Methods

Prospective longitudinal multicentre study in which individuals with Lynch syndrome collected faeces before and after high-quality surveillance colonoscopy. VOC-patterns were analysed using field asymmetric ion mobility spectrometry (FAIMS) and gas chromatography-ion mobility spectrometry (GC-IMS) followed by machine learning pipelines, and combined with FIT at 2.55 μg Hb/g faeces. Gas chromatography time-of-flight mass spectrometry analysed individual VOC abundance.

Results

Among 200 included individuals (57% female, median 51 years), 62 had relevant neoplasia at colonoscopy: 3 CRC, 6 advanced adenoma (AA), 3 advanced serrated lesion (ASL), and 50 non-advanced adenoma (NAA). Respective sensitivity and negative predictive value for CRC and AA (and also ASL in case of FAIMS) were 100% and 100% using FAIMS (54% specificity), and 89% and 99% using GC-IMS (58% specificity). Respective sensitivity and specificity for any relevant neoplasia were 88% and 44% (FAIMS) and 84% and 28% (GC-IMS); accuracy did not significantly improve upon VOC-FIT. VOC-patterns differed before and after polypectomy (AUC 0.70). NAA showed decreased faecal abundance of butanal, 2-oxohexane, dimethyldisulphide and dimethyltrisulphide.

Conclusions

In Lynch syndrome, faecal VOCs may be a promising strategy for postponing colonoscopy and for follow-up after polypectomy. Our results serve as a stepping stone for large validation studies.

Trial Registration

NL8749

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检测林奇综合征结直肠肿瘤的粪便挥发性有机化合物--前瞻性纵向多中心研究

无创生物标志物可降低林奇综合征患者结肠镜检查后的结直肠癌（CRC）发病率和结肠镜检查的过度使用。与粪便免疫化学检验（FIT）不同，粪便挥发性有机化合物（VOC）可准确检测晚期和非晚期结直肠肿瘤。

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来源期刊

Alimentary Pharmacology & Therapeutics 医学-胃肠肝病学

CiteScore

15.60

自引率

7.90%

发文量

527

审稿时长

3-6 weeks

期刊介绍： Alimentary Pharmacology & Therapeutics is a global pharmacology journal focused on the impact of drugs on the human gastrointestinal and hepato-biliary systems. It covers a diverse range of topics, often with immediate clinical relevance to its readership.