title: Pulmonary venous blood sampling significantly increases the yield of circulating tumor cells in early-stage lung cancer.
abstract: OBJECTIVE
  To identify circulating tumor cells (CTCs) in the blood of patients with early-stage lung cancer and to show that sampling pulmonary vein (PV) blood using microfluidic chip technology will yield significantly more CTCs. Improving early detection of lung cancer is critical to improving lung cancer survival. Reproducible detection of CTCs is limited currently in early stage tumors.
  
  
  METHODS
  Patients undergoing pulmonary resection had PV blood drawn before resection. Peripheral blood was sampled at preoperative, intraoperative, and postoperative times. Samples were analyzed on microfluidic chips using antibody-based capture.
  
  
  RESULTS
  A total of 32 patients with primary lung cancer were evaluated. Twenty patients had 1 or more CTCs detected in at least 1 sample (62.5%). The mean number of CTCs from peripheral vein sources at the preoperative, intraoperative, and postoperative time points was 1.3, 1.9, and 0.6 respectively. The average number of CTCs in the PV was 340.0 (range, 0.0-5422.50; P > .01). When PV CTCs were present, the number of CTCs was correlated with pathological tumor size (P = .0236). The number of PV CTCs was not correlated with any other clinical feature (eg, smoking status, preoperative or postoperative stage). Furthermore, the number of PV CTCs was significantly higher when preoperative bronchoscopic biopsy was performed, compared with computed tomography-guided biopsy (P = .0311). Seven patients had evidence of CTC clusters, or microemboli.
  
  
  CONCLUSIONS
  With a single vein draining the entire tumor basin, lung cancers are unique, allowing the high-yield isolation of CTCs from the PV. This method may facilitate future studies to improve the detection and analysis of early-stage lung CTCs.
authors.affiliation: Section of Thoracic Surgery, Department of Surgery, University of Michigan, Ann Arbor, Michigan. Electronic address: reddyrm@med.umich.edu.
authors.forename: Rishindra M
authors.initials: RM
authors.lastname: Reddy
authors.affiliation: Department of Chemical Engineering, University of Michigan, Ann Arbor, Michigan.
authors.forename: Vasudha
authors.initials: V
authors.lastname: Murlidhar
authors.affiliation: Department of Biostatistics, University of Michigan, Ann Arbor, Michigan.
authors.forename: Lili
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Section of Thoracic Surgery, Department of Surgery, University of Michigan, Ann Arbor, Michigan.
authors.forename: Svetlana
authors.initials: S
authors.lastname: Grabauskiene
authors.affiliation: Department of Chemical Engineering, University of Michigan, Ann Arbor, Michigan.
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Division of Hematology/Oncology, Department of Medicine, University of Michigan, Ann Arbor, Michigan.
authors.forename: Nithya
authors.initials: N
authors.lastname: Ramnath
authors.affiliation: Section of Thoracic Surgery, Department of Surgery, University of Michigan, Ann Arbor, Michigan.
authors.forename: Jules
authors.initials: J
authors.lastname: Lin
authors.affiliation: Section of Thoracic Surgery, Department of Surgery, University of Michigan, Ann Arbor, Michigan.
authors.forename: Andrew C
authors.initials: AC
authors.lastname: Chang
authors.affiliation: Section of Thoracic Surgery, Department of Surgery, University of Michigan, Ann Arbor, Michigan.
authors.forename: Phillip
authors.initials: P
authors.lastname: Carrott
authors.affiliation: Section of Thoracic Surgery, Department of Surgery, University of Michigan, Ann Arbor, Michigan.
authors.forename: William
authors.initials: W
authors.lastname: Lynch
authors.affiliation: Section of Thoracic Surgery, Department of Surgery, University of Michigan, Ann Arbor, Michigan.
authors.forename: Mark B
authors.initials: MB
authors.lastname: Orringer
authors.affiliation: Section of Thoracic Surgery, Department of Surgery, University of Michigan, Ann Arbor, Michigan.
authors.forename: David G
authors.initials: DG
authors.lastname: Beer
authors.affiliation: Department of Chemical Engineering, University of Michigan, Ann Arbor, Michigan.
authors.forename: Sunitha
authors.initials: S
authors.lastname: Nagrath
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D055088:Early Detection of Cancer; D005260:Female; D006801:Humans; D056656:Lab-On-A-Chip Devices; D008175:Lung Neoplasms / Q000097:blood / Q000473:pathology* / Q000601:surgery; D008297:Male; D046208:Microchip Analytical Procedures; D008875:Middle Aged; D009367:Neoplasm Staging; D009360:Neoplastic Cells, Circulating / Q000473:pathology*; D011013:Pneumonectomy; D011237:Predictive Value of Tests; D011446:Prospective Studies; D011667:Pulmonary Veins; D013997:Time Factors; D016896:Treatment Outcome
keywords: circulating tumor cells; early cancer detection; lung cancer