title: Lymph node metastasis density and growth pattern as independent prognostic factors in advanced esophageal squamous cell carcinoma.
abstract: BACKGROUND
  Esophageal cancer is one of the leading types of cancer, and it is a particularly deadly form of malignancy. TNM classification is the most common staging system, but it has been reported that prognosis is not reflected adequately by this classification. The purpose of this study was to clarify independent prognostic factors in esophageal squamous cell carcinoma (ESCC), a dominant type of esophageal cancer in Japan, to broaden the staging system to improve its predictive value. Thus staging could be expanded to make the prognosis a valuable clinical tool, and to improve knowledge of the biological traits of advanced ESCC.
  
  
  METHODS
  The present study included 121 patients with advanced ESCC (stage II to IVA) treated by esophagectomy between 1990 and 2003 at the Kitasato University Higashi Hospital.
  
  
  RESULTS
  Univariate prognostic analysis of the disease-specific survival revealed that TNM stage (p < 0.0001), lymph node metastasis density over 10% (ND10; p < 0.0001), R-category (p = 0.003), intramural metastasis within the esophagus (IM; p = 0.009), growth pattern (p = 0.01), and size of tumor (p = 0.02) were significantly associated with a poor outcome in advanced ESCC. Multivariate analysis confirmed that growth pattern (p = 0.02, HR = 3.1) and ND10 (p = 0.02, HR = 2.0) were finally remnant prognostic factors independent of TNM stage. Growth pattern was prominent in stage II, whereas ND10 was directly proportional to stage progression and characteristics to stage IV disease. Interestingly, ND20, the most malignant phenotype of ESCC, was the only prognostic determinant, even in stage IV disease.
  
  
  CONCLUSIONS
  From the present study, we concluded that progression of lymph node density is characteristic of a life-threatening phenotype of advanced ESCC, and it should be employed as a therapeutic target to improve patient survival. Growth pattern is an alternative target characteristic of less advanced ESCC. Both of these parameters may be applied as useful clinical tools in the management of patients with advanced esophageal cancer.
authors.affiliation: Department of Surgery, Kitasato University Higashi Hospital, Asamizodai 2-1-1, Sagamihara 228-8520 Kanagawa, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Ooki
authors.forename: Keishi
authors.initials: K
authors.lastname: Yamashita
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Kobayashi
authors.forename: Natsuya
authors.initials: N
authors.lastname: Katada
authors.forename: Shinichi
authors.initials: S
authors.lastname: Sakuramoto
authors.forename: Shiroh
authors.initials: S
authors.lastname: Kikuchi
authors.forename: Masahiko
authors.initials: M
authors.lastname: Watanabe
mesh_terms: D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000401:mortality* / Q000473:pathology*; D004938:Esophageal Neoplasms / Q000401:mortality* / Q000473:pathology*; D005260:Female; D006801:Humans; D008198:Lymph Nodes / Q000473:pathology*; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011379:Prognosis