title: Significant increase in circulating tumour cells in pulmonary venous blood during surgical manipulation in patients with primary lung cancer.
abstract: OBJECTIVE
  Circulating tumour cells (CTCs) are tumour cells shed from a primary tumour and circulate in the peripheral blood after passing through the drainage vein. In previous studies, we showed that high numbers of CTCs were detected in the drainage pulmonary venous blood of most patients with resectable primary lung cancer, whereas only low numbers of CTCs were detected in the peripheral blood of some patients. Accordingly, this prospective study was conducted to assess changes in CTCs in the drainage pulmonary vein (PV) during lung cancer surgery.
  
  
  METHODS
  A total of 30 consecutive peripheral-type primary lung cancer patients who underwent lobectomy (or right upper and middle bilobectomy) through open thoracotomy were included. For each patient, 2.5 ml of blood was sampled from the lobar PV of the primary tumour site before and after surgical manipulation for lobectomy. The CTCs were evaluated quantitatively with the CellSearch® system.
  
  
  RESULTS
  Before surgical manipulation, CTCs were detected in PV blood in the majority of patients (22 of 30, 73.3%), although CTCs were detected in peripheral blood in only two patients (6.7%). The median number of CTCs in the PV (pvCTC-count) before surgical manipulation was 4.0 cells/2.5 ml, and there was no significant correlation between pvPV-count and any clinicopathological characteristic, including tumour size, progression and histological type. After surgical manipulation, at the time of completion of the lobectomy, the pvCTC-count significantly increased (median, 60.0 cells/2.5 ml; P = 0.001). The increase in pvCTC-count was significantly associated with microscopic lymphatic tumour invasion (ly); pvCTC-count significantly increased in ly-positive patients (pvCTC-count before and after surgical manipulation, 4.0 and 90.5 cells/2.5 ml, respectively; P = 0.006), but not in ly-negative patients (3.5 and 7.0 cells/2.5 ml, respectively; P = 0.153). The increase in pvCTC-count was not significantly associated with any other clinicopathological factor or with any surgical procedure, including the sequence of vessel interruption.
  
  
  CONCLUSIONS
  We documented a significant increase in CTC count in drainage PV blood after surgical manipulation, especially in tumours with lymphatic invasion. We are awaiting survival data at 5 year follow-up examination, which may provide clinical significance of the pvCTC-count.
authors.affiliation: Department of Thoracic Surgery, Hyogo College of Medicine, Nishinomiya, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Hashimoto
authors.affiliation: Second Department of Surgery (Chest Surgery), University of Occupational and Environmental Health, Kitakyusyu, Japan ftanaka@med.uoeh-u.ac.jp.
authors.forename: Fumihiro
authors.initials: F
authors.lastname: Tanaka
authors.affiliation: Department of Thoracic Surgery, Hyogo College of Medicine, Nishinomiya, Japan.
authors.forename: Kazue
authors.initials: K
authors.lastname: Yoneda
authors.affiliation: Department of Thoracic Surgery, Hyogo College of Medicine, Nishinomiya, Japan.
authors.forename: Teruhisa
authors.initials: T
authors.lastname: Takuwa
authors.affiliation: Department of Thoracic Surgery, Hyogo College of Medicine, Nishinomiya, Japan.
authors.forename: Seiji
authors.initials: S
authors.lastname: Matsumoto
authors.affiliation: Itami City Hospital, Itami, Japan.
authors.forename: Yoshitomo
authors.initials: Y
authors.lastname: Okumura
authors.affiliation: Department of Thoracic Surgery, Hyogo College of Medicine, Nishinomiya, Japan.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Kondo
authors.affiliation: Department of Thoracic Oncology, Hyogo College of Medicine, Nishinomiya, Japan.
authors.forename: Noriaki
authors.initials: N
authors.lastname: Tsubota
authors.affiliation: Department of Pathology, Hyogo College of Medicine, Nishinomiya, Japan.
authors.forename: Tohru
authors.initials: T
authors.lastname: Tsujimura
authors.affiliation: Division of Respiratory Medicine, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan.
authors.forename: Chiharu
authors.initials: C
authors.lastname: Tabata
authors.affiliation: Division of Respiratory Medicine, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Nakano
authors.affiliation: Department of Thoracic Surgery, Hyogo College of Medicine, Nishinomiya, Japan.
authors.forename: Seiki
authors.initials: S
authors.lastname: Hasegawa
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology* / Q000601:surgery*; D008207:Lymphatic Metastasis; D008208:Lymphatic System / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009360:Neoplastic Cells, Circulating / Q000473:pathology*; D011013:Pneumonectomy / Q000009:adverse effects*; D011446:Prospective Studies; D011667:Pulmonary Veins; D013997:Time Factors; D016896:Treatment Outcome
keywords: Circulating tumour cell; Lung cancer; Pulmonary vein; Surgical manipulation