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A novel methodology for in vivo endoscopic phenotyping of colorectal cancer based on real-time analysis of the mucosal lipidome: a prospective observational study of the iKnife

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Title: A novel methodology for in vivo endoscopic phenotyping of colorectal cancer based on real-time analysis of the mucosal lipidome: a prospective observational study of the iKnife
Authors: Alexander, J
Gildea, L
Balog, J
Speller, A
McKenzie, J
Muirhead, L
Scott, A
Kontovounisios, C
Rasheed, S
Teare, J
Hoare, J
Veselkov, K
Goldin, R
Tekkis, P
Darzi, A
Nicholson, J
Kinross, J
Takats, Z
Item Type: Journal Article
Abstract: Background: This pilot study assessed the diagnostic accuracy of rapid evaporative ionization mass spectrometry (REIMS) in colorectal cancer (CRC) and colonic adenomas. Methods: Patients undergoing elective surgical resection for CRC were recruited at St. Mary’s Hospital London and The Royal Marsden Hospital, UK. Ex vivo analysis was performed using a standard electrosurgery handpiece with aspiration of the electrosurgical aerosol to a Xevo G2-S iKnife QTof mass spectrometer (Waters Corporation). Histological examination was performed for validation purposes. Multivariate analysis was performed using principal component analysis and linear discriminant analysis in Matlab 2015a (Mathworks, Natick, MA). A modified REIMS endoscopic snare was developed (Medwork) and used prospectively in five patients to assess its feasibility during hot snare polypectomy. Results: Twenty-eight patients were recruited (12 males, median age 71, range 35–89). REIMS was able to reliably distinguish between cancer and normal adjacent mucosa (NAM) (AUC 0.96) and between NAM and adenoma (AUC 0.99). It had an overall accuracy of 94.4 % for the detection of cancer versus adenoma and an adenoma sensitivity of 78.6 % and specificity of 97.3 % (AUC 0.99) versus cancer. Long-chain phosphatidylserines (e.g., PS 22:0) and bacterial phosphatidylglycerols were over-expressed on cancer samples, while NAM was defined by raised plasmalogens and triacylglycerols expression and adenomas demonstrated an over-expression of ceramides. REIMS was able to classify samples according to tumor differentiation, tumor budding, lymphovascular invasion, extramural vascular invasion and lymph node micrometastases (AUC’s 0.88, 0.87, 0.83, 0.81 and 0.81, respectively). During endoscopic deployment, colonoscopic REIMS was able to detect target lipid species such as ceramides during hot snare polypectomy. Conclusion: REIMS demonstrates high diagnostic accuracy for tumor type and for established histological features of poor prognostic outcome in CRC based on a multivariate analysis of the mucosal lipidome. REIMS could augment endoscopic and imaging technologies for precision phenotyping of colorectal cancer.
Issue Date: 8-Aug-2016
Date of Acceptance: 12-Jul-2016
URI: http://hdl.handle.net/10044/1/38835
DOI: https://dx.doi.org/10.1007/s00464-016-5121-5
ISSN: 1432-2218
Publisher: Springer Verlag (Germany)
Start Page: 1361
End Page: 1370
Journal / Book Title: Surgical Endoscopy and Other Interventional Techniques
Volume: 31
Issue: 3
Copyright Statement: © The Author(s) 2016. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
Sponsor/Funder: National Institute for Health Research
Imperial College Healthcare NHS Trust- BRC Funding
Imperial College Healthcare NHS Trust- BRC Funding
Commission of the European Communities
Micromass UK Ltd
Funder's Grant Number: NF-SI-0510-10186
RDB03 79560
RDB01 79560
617896
ICL 01/02/03
Keywords: Science & Technology
Life Sciences & Biomedicine
Surgery
Rapid evaporative ionization mass spectrometry
Colorectal cancer
Metabolic
IONIZATION MASS-SPECTROMETRY
TISSUE
IDENTIFICATION
METABOLISM
POLYPS
Adenoma
Adult
Aged
Aged, 80 and over
Ceramides
Colonoscopy
Colorectal Neoplasms
Female
Humans
Intestinal Mucosa
Intraoperative Care
Male
Mass Spectrometry
Middle Aged
Phosphatidylglycerols
Phosphatidylserines
Pilot Projects
Plasmalogens
Prospective Studies
Sensitivity and Specificity
Triglycerides
1103 Clinical Sciences
Publication Status: Published
Appears in Collections:Division of Surgery
Department of Medicine
Faculty of Medicine



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