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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Publication Date
2017-03Author
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
Type
Journal Article
Metadata
Show full item recordAbstract
<h4>Background</h4>This pilot study assessed the diagnostic accuracy of rapid evaporative ionization mass spectrometry (REIMS) in colorectal cancer (CRC) and colonic adenomas.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusion</h4>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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Licenseref URL
https://creativecommons.org/licenses/by/4.0Version of record
Subject
Intestinal Mucosa
Humans
Adenoma
Colorectal Neoplasms
Ceramides
Triglycerides
Phosphatidylglycerols
Phosphatidylserines
Plasmalogens
Colonoscopy
Intraoperative Care
Sensitivity and Specificity
Prospective Studies
Pilot Projects
Adult
Aged
Aged, 80 and over
Middle Aged
Female
Male
Mass Spectrometry
Language
eng
Date accepted
2016-07-12
License start date
2017-03
Citation
Surgical endoscopy, 2017, 31 (3), pp. 1361 - 1370