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Original Investigation
May 1, 2019

Effect of Vein-First vs Artery-First Surgical Technique on Circulating Tumor Cells and Survival in Patients With Non–Small Cell Lung Cancer: A Randomized Clinical Trial and Registry-Based Propensity Score Matching Analysis

Author Affiliations
  • 1Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu, China
  • 2Western China Collaborative Innovation Center for Early Diagnosis and Multidisciplinary Therapy of Lung Cancer, Sichuan University, Chengdu, China
  • 3Department of Thoracic Surgery, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
  • 4Department of Thoracic Surgery, Daping Hospital, Third Military Medical University, Chongqing, China
  • 5Department of Evidence-Based Medicine and Clinical Epidemiology, West China Hospital, Sichuan University, Chengdu, China
JAMA Surg. 2019;154(7):e190972. doi:10.1001/jamasurg.2019.0972
Key Points

Question  Can ligating the effluent veins first during surgery reduce the dissemination of tumor cells in patients with non–small cell lung cancer?

Findings  In this randomized clinical trial of 86 patients randomized to receive vein-first vs artery-first ligation during surgery, incremental change of circulating tumor cells was observed in 65% of patients in the artery-first group and 31.6% of patients in the vein-first group. Five-year overall survival, disease-free survival, and lung cancer–specific survival for the patients in the vein-first group were significantly better than those in the artery-first group.

Meaning  Ligating the effluent veins first during operation may be more in line with cancer treatment principles and should be recommended for lung cancer surgery.


Importance  It is important to develop a surgical technique to reduce dissemination of tumor cells into the blood during surgery.

Objective  To compare the outcomes of different sequences of vessel ligation during surgery on the dissemination of tumor cells and survival in patients with non–small cell lung cancer.

Design, Setting, and Participants  This multicenter, randomized clinical trial was conducted from December 2016 to March 2018 with patients with non–small cell lung cancer who received thoracoscopic lobectomy in West China Hospital, Daping Hospital, and Sichuan Cancer Hospital. To further compare survival outcomes of the 2 procedures, we reviewed the Western China Lung Cancer database (2005-2017) using the same inclusion criteria.

Interventions  Vein-first procedure vs artery-first procedure.

Main Outcomes and Measures  Changes in folate receptor–positive circulating tumor cells (FR+CTCs) after surgery and 5-year overall, disease-free, and lung cancer–specific survival.

Results  A total of 86 individuals were randomized; 22 patients (25.6%) were younger and 64 (74.4%) older than 60 years. Of these, 78 patients were analyzed. After surgery, an incremental change in FR+CTCs was observed in 26 of 40 patients (65.0%) in the artery-first group and 12 of 38 (31.6%) in the vein-first group (P = .003) (median change, 0.73 [interquartile range (IQR), −0.86 to 1.58] FU per 3 mL vs −0.50 [IQR, −2.53 to 0.79] FU per 3 mL; P = .006). Multivariate analysis confirmed that the artery-first procedure was a risk factor for FR+CTC increase during surgery (hazard ratio [HR], 4.03 [95% CI, 1.53-10.63]; P = .005). The propensity-matched analysis included 420 patients (210 with vein-first procedures and 210 with artery-first procedures). The vein-first group had significantly better outcomes than the artery-first group for 5-year overall survival (73.6% [95% CI, 64.4%-82.8%] vs 57.6% [95% CI, 48.4%-66.8%]; P = .002), disease-free survival (63.6% [95% CI, 55.4%-73.8%] vs 48.4% [95% CI, 40.0%-56.8%]; P = .001), and lung cancer–specific survival (76.4% [95% CI, 67.6%-85.2%] vs 59.9% [95% CI, 50.5%-69.3%]; P = .002). Multivariate analyses revealed that the artery-first procedure was a prognostic factor of poorer 5-year overall survival (HR, 1.65 [95% CI, 1.07-2.56]; P = .03), disease-free survival (HR, 1.43 [95% CI, 1.01-2.04]; P = .05) and lung cancer–specific survival (HR = 1.65 [95% CI, 1.04-2.61]; P = .03).

Conclusions and Relevance  Ligating effluent veins first during surgery may reduce tumor cell dissemination and improve survival outcomes in patients with non–small cell lung cancer.

Trial Registration  ClinicalTrials.gov identifier: NCT03436329

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