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Published in: Surgical Endoscopy 3/2017

Open Access 01-03-2017

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: James Alexander, Louise Gildea, Julia Balog, Abigail Speller, James McKenzie, Laura Muirhead, Alasdair Scott, Christos Kontovounisios, Shanawaz Rasheed, Julian Teare, Jonathan Hoare, Kirill Veselkov, Robert Goldin, Paris Tekkis, Ara Darzi, Jeremy Nicholson, James Kinross, Zoltan Takats

Published in: Surgical Endoscopy | Issue 3/2017

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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.
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Metadata
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
James Alexander
Louise Gildea
Julia Balog
Abigail Speller
James McKenzie
Laura Muirhead
Alasdair Scott
Christos Kontovounisios
Shanawaz Rasheed
Julian Teare
Jonathan Hoare
Kirill Veselkov
Robert Goldin
Paris Tekkis
Ara Darzi
Jeremy Nicholson
James Kinross
Zoltan Takats
Publication date
01-03-2017
Publisher
Springer US
Published in
Surgical Endoscopy / Issue 3/2017
Print ISSN: 0930-2794
Electronic ISSN: 1432-2218
DOI
https://doi.org/10.1007/s00464-016-5121-5

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