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.
abstract: This pilot study assessed the diagnostic accuracy of rapid evaporative ionization mass spectrometry (REIMS) in colorectal cancer (CRC) and colonic adenomas.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors: Department of Surgery and Cancer, Imperial College London, St. Mary's Hospital, Praed Street, London, NW1 1SQ, UK.
authors: James
authors: J
authors: Alexander
authors: Department of Surgery and Cancer, Imperial College London, St. Mary's Hospital, Praed Street, London, NW1 1SQ, UK.
authors: Louise
authors: L
authors: Gildea
authors: Waters Corporation, Wilmslow, UK.
authors: Julia
authors: J
authors: Balog
authors: Department of Histopathology, Imperial College London, London, UK.
authors: Abigail
authors: A
authors: Speller
authors: Department of Surgery and Cancer, Imperial College London, St. Mary's Hospital, Praed Street, London, NW1 1SQ, UK.
authors: James
authors: J
authors: McKenzie
authors: Department of Surgery and Cancer, Imperial College London, St. Mary's Hospital, Praed Street, London, NW1 1SQ, UK.
authors: Laura
authors: L
authors: Muirhead
authors: Department of Surgery and Cancer, Imperial College London, St. Mary's Hospital, Praed Street, London, NW1 1SQ, UK.
authors: Alasdair
authors: A
authors: Scott
authors: Department of Colorectal Surgery, Royal Marsden Hospital NHS Trust, London, UK.
authors: Christos
authors: C
authors: Kontovounisios
authors: Department of Colorectal Surgery, Royal Marsden Hospital NHS Trust, London, UK.
authors: Shanawaz
authors: S
authors: Rasheed
authors: Department of Surgery and Cancer, Imperial College London, St. Mary's Hospital, Praed Street, London, NW1 1SQ, UK.
authors: Julian
authors: J
authors: Teare
authors: Department of Gastroenterology, Imperial Healthcare NHS Trust, London, UK.
authors: Jonathan
authors: J
authors: Hoare
authors: Department of Surgery and Cancer, Imperial College London, St. Mary's Hospital, Praed Street, London, NW1 1SQ, UK.
authors: Kirill
authors: K
authors: Veselkov
authors: Department of Histopathology, Imperial College London, London, UK.
authors: Robert
authors: R
authors: Goldin
authors: Department of Colorectal Surgery, Royal Marsden Hospital NHS Trust, London, UK.
authors: Paris
authors: P
authors: Tekkis
authors: Department of Surgery and Cancer, Imperial College London, St. Mary's Hospital, Praed Street, London, NW1 1SQ, UK.
authors: Ara
authors: A
authors: Darzi
authors: Department of Surgery and Cancer, Imperial College London, St. Mary's Hospital, Praed Street, London, NW1 1SQ, UK.
authors: Jeremy
authors: J
authors: Nicholson
authors: Department of Surgery and Cancer, Imperial College London, St. Mary's Hospital, Praed Street, London, NW1 1SQ, UK. j.kinross@imperial.ac.uk.
authors: James
authors: J
authors: Kinross
authors: Department of Surgery and Cancer, Imperial College London, St. Mary's Hospital, Praed Street, London, NW1 1SQ, UK.
authors: Zoltan
authors: Z
authors: Takats
mesh_terms: D000236:Adenoma / Q000378:metabolism / Q000473:pathology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002518:Ceramides / Q000378:metabolism; D003113:Colonoscopy; D015179:Colorectal Neoplasms / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism* / Q000473:pathology; D007430:Intraoperative Care; D008297:Male; D013058:Mass Spectrometry / Q000379:methods*; D008875:Middle Aged; D010715:Phosphatidylglycerols / Q000378:metabolism; D010718:Phosphatidylserines / Q000378:metabolism; D010865:Pilot Projects; D010955:Plasmalogens / Q000378:metabolism; D011446:Prospective Studies; D012680:Sensitivity and Specificity; D014280:Triglycerides / Q000378:metabolism
chemical_list: D002518:Ceramides; D010715:Phosphatidylglycerols; D010718:Phosphatidylserines; D010955:Plasmalogens; D014280:Triglycerides
keywords: Colorectal cancer; Metabolic; Rapid evaporative ionization mass spectrometry