title: Identification and Validation of Lymphovascular Invasion as a Prognostic and Staging Factor in Node-Negative Esophageal Squamous Cell Carcinoma.
abstract: BACKGROUND
  Lymphovascular invasion (LVI) is a histopathological feature that is associated with an increased risk for micrometastasis. The aim of this study was to determine the prognostic and staging value of LVI among patients with esophageal squamous cell carcinoma (ESCC) undergoing esophagectomy.
  
  
  METHODS
  A prospective database of patients with ESCC was used to retrospectively analyze 666 cases to identify the relationship between LVI and survival, and to evaluate predictive accuracy of prognosis after combining LVI and the tumor, node, and metastasis (TNM) system. Pathological slides were reassessed by gastrointestinal pathologists according to the strict criteria; 1000-bootstrap resampling was used for internal validation, and 222 cases from an independent multicenter database were used for external validation.
  
  
  RESULTS
  LVI was present in 33.8% of patients, and the proportion increased with advancing T and N classification. LVI was an independent predictor of unfavorable disease-specific survival (DSS) (hazard ratio = 1.59, 95% confidence interval: 1.30-1.94) and disease-free survival (DFS) (hazard ratio = 1.62, 95% confidence interval: 1.32-1.98) after T classification. Among node-negative patients, LVI and T classification were two independent predictors of DSS and DFS (p < 0.001). The risk score model combing LVI and T classification improved the predictive accuracy of the TNM system for DSS and DFS by 3.5% and 4.8%, respectively (p < 0.001). The external validation showed congruent results. The DSS of TxN0MO disease with LVI was similar to the DSS of TxN1M0 (both p > 0.05). In contrast, LVI was not associated with DSS or DFS among node-positive patients.
  
  
  CONCLUSIONS
  The independent prognostic significance of LVI existed only in node-negative patients with ESCC, and the combination of LVI and the TNM system enhanced the predictive accuracy of prognosis. After confirmation, node-negative patients with LVI might be considered for upstaging in pathological staging.
authors.affiliation: Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People's Republic of China; Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, People's Republic of China; Guangdong Esophageal Cancer Institute, Guangzhou, People's Republic of China.
authors.forename: Qingyuan
authors.initials: Q
authors.lastname: Huang
authors.affiliation: Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People's Republic of China; Guangdong Esophageal Cancer Institute, Guangzhou, People's Republic of China.
authors.forename: Kongjia
authors.initials: K
authors.lastname: Luo
authors.affiliation: Fujian Medical University Union Hospital, Fuzhou, People's Republic of China.
authors.forename: Chun
authors.initials: C
authors.lastname: Chen
authors.affiliation: Cancer Hospital of Shantou University Medical College, Shantou, People's Republic of China.
authors.forename: Geng
authors.initials: G
authors.lastname: Wang
authors.affiliation: Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People's Republic of China.
authors.forename: Jietian
authors.initials: J
authors.lastname: Jin
authors.affiliation: Taizhou Hospital, Taizhou, People's Republic of China.
authors.forename: Min
authors.initials: M
authors.lastname: Kong
authors.affiliation: Fujian Medical University Union Hospital, Fuzhou, People's Republic of China; Xiamen Traditional Hospital, Xiamen, People's Republic of China.
authors.forename: Bifeng
authors.initials: B
authors.lastname: Li
authors.affiliation: Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People's Republic of China; Guangdong Esophageal Cancer Institute, Guangzhou, People's Republic of China.
authors.forename: Qianwen
authors.initials: Q
authors.lastname: Liu
authors.affiliation: School of Public Health, the University of Hong Kong, Hong Kong, People's Republic of China.
authors.forename: Jinhui
authors.initials: J
authors.lastname: Li
authors.affiliation: Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People's Republic of China; Guangdong Esophageal Cancer Institute, Guangzhou, People's Republic of China.
authors.forename: Tiehua
authors.initials: T
authors.lastname: Rong
authors.affiliation: Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, People's Republic of China.
authors.forename: Haiquan
authors.initials: H
authors.lastname: Chen
authors.affiliation: Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People's Republic of China; Guangdong Esophageal Cancer Institute, Guangzhou, People's Republic of China.
authors.forename: Lanjun
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Cancer Hospital of Shantou University Medical College, Shantou, People's Republic of China.
authors.forename: Yuping
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Taizhou Hospital, Taizhou, People's Republic of China.
authors.forename: Chengchu
authors.initials: C
authors.lastname: Zhu
authors.affiliation: Fujian Medical University Union Hospital, Fuzhou, People's Republic of China.
authors.forename: Bin
authors.initials: B
authors.lastname: Zheng
authors.affiliation: Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People's Republic of China; Guangdong Esophageal Cancer Institute, Guangzhou, People's Republic of China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wen
authors.affiliation: Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People's Republic of China; Guangdong Esophageal Cancer Institute, Guangzhou, People's Republic of China.
authors.forename: Yuzhen
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People's Republic of China; Guangdong Esophageal Cancer Institute, Guangzhou, People's Republic of China.
authors.forename: Zihui
authors.initials: Z
authors.lastname: Tan
authors.affiliation: Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People's Republic of China; Guangdong Esophageal Cancer Institute, Guangzhou, People's Republic of China.
authors.forename: Xiuying
authors.initials: X
authors.lastname: Xie
authors.affiliation: Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People's Republic of China; Guangdong Esophageal Cancer Institute, Guangzhou, People's Republic of China.
authors.forename: Hong
authors.initials: H
authors.lastname: Yang
authors.affiliation: Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People's Republic of China; Guangdong Esophageal Cancer Institute, Guangzhou, People's Republic of China. Electronic address: fu_jianhua@126.com.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Fu
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000473:pathology*; D004938:Esophageal Neoplasms / Q000473:pathology*; D000077277:Esophageal Squamous Cell Carcinoma; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D011379:Prognosis; D011446:Prospective Studies; D012189:Retrospective Studies
keywords: Esophageal squamous cell carcinoma; Lymphovascular invasion; Prognosis; Tumor staging