• Sam E Mason, Eftychios Manoli, James L Alexander, Liam Poynter, Lauren Ford, Petra Paizs, Afeez Adebesin, James S McKenzie, Francesca Rosini, Rob Goldin, Ara Darzi, Zoltan Takats, and James M Kinross.
• Department of Surgery and Cancer, Imperial College, London.
• Ann. Surg. 2023 Mar 1; 277 (3): e569e577e569-e577.

ObjectiveRapid evaporative ionization mass spectrometry (REIMS) is a metabolomic technique analyzing tissue metabolites, which can be applied intraoperatively in real-time. The objective of this study was to profile the lipid composition of colorectal tissues using REIMS, assessing its accuracy for real-time tissue recognition and risk-stratification.Summary Background DataMetabolic dysregulation is a hallmark feature of carcinogenesis; however, it remains unknown if this can be leveraged for real-time clinical applications in colorectal disease.MethodsPatients undergoing colorectal resection were included, with carcinoma, adenoma and paired-normal mucosa sampled. Ex vivo analysis with REIMS was conducted using monopolar diathermy, with the aerosol aspirated into a Xevo G2S QToF mass spectrometer. Negatively charged ions over 600 to 1000 m/z were used for univariate and multivariate functions including linear discriminant analysis.ResultsA total of 161 patients were included, generating 1013 spectra. Unique lipidomic profiles exist for each tissue type, with REIMS differentiating samples of carcinoma, adenoma, and normal mucosa with 93.1% accuracy and 96.1% negative predictive value for carcinoma. Neoplasia (carcinoma or adenoma) could be predicted with 96.0% accuracy and 91.8% negative predictive value. Adenomas can be risk-stratified by grade of dysplasia with 93.5% accuracy, but not histological subtype. The structure of 61 lipid metabolites was identified, revealing that during colorectal carcinogenesis there is progressive increase in relative abundance of phosphatidylglycerols, sphingomyelins, and mono-unsaturated fatty acid-containing phospholipids.ConclusionsThe colorectal lipidome can be sampled by REIMS and leveraged for accurate real-time tissue recognition, in addition to riskstratification of colorectal adenomas. Unique lipidomic features associated with carcinogenesis are described.Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.

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