title: Esophageal submucosa: the watershed for esophageal cancer.
abstract: OBJECTIVE
  Submucosal esophageal cancers (pT1b) are considered superficial, implying good survival. However, some are advanced, metastasizing to regional lymph nodes. Interplay of cancer characteristics and lymphatic anatomy may create a watershed, demarcating low-risk from high-risk cancers. Therefore, we characterized submucosal cancers according to depth of invasion and identified those with high likelihood of lymph node metastases and poor survival.
  
  
  METHODS
  From 1983 to 2010, 120 patients underwent esophagectomy for submucosal cancers at Cleveland Clinic. Correlations were sought among cancer characteristics (location, dimensions, histopathologic cell type, histologic grade, and lymphovascular invasion [LVI]), and their associations with lymph node metastasis were identified by logistic regression. Associations with mortality were identified by Cox regression.
  
  
  RESULTS
  As submucosal invasion increased, cancer length (P < .001), width (P < .001), area (P < .001), LVI (P = .007), and grade (P = .05) increased. Invasion of the deep submucosa (P < .001) and LVI (P = .06) predicted lymph node metastases: 45% (23/51) of deep versus 10% (3/29) of middle-third and 7.5% (3/40) of inner-third cancers had lymph node metastases, as did 46% (12/26) with LVI versus 18% (17/94) without. Older age and lymph node metastases predicted worse 5-year survival: 94% for younger pN0 patients, 62% for older pN0 patients, and 36% for pN1-2 patients regardless of age.
  
  
  CONCLUSIONS
  Submucosal cancer characteristics and lymphatic anatomy create a watershed for regional lymph node metastases in the deep submucosa. This previously unrecognized divide distinguishes superficial submucosal cancers with good survival from deep submucosal cancers with poor survival. Aggressive therapy of more superficial cancers is critical before submucosal invasion occurs.
authors.affiliation: Heart and Vascular Institute, Department of Thoracic and Cardiovascular Surgery, Cleveland, OH, USA.
authors.forename: Siva
authors.initials: S
authors.lastname: Raja
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Rice
authors.forename: John R
authors.initials: JR
authors.lastname: Goldblum
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Rybicki
authors.forename: Sudish C
authors.initials: SC
authors.lastname: Murthy
authors.forename: David P
authors.initials: DP
authors.lastname: Mason
authors.forename: Eugene H
authors.initials: EH
authors.lastname: Blackstone
mesh_terms: D000230:Adenocarcinoma / Q000401:mortality / Q000473:pathology*; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000401:mortality / Q000473:pathology*; D004938:Esophageal Neoplasms / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D004947:Esophagus / Q000473:pathology*; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D009092:Mucous Membrane / Q000473:pathology; D009361:Neoplasm Invasiveness; D011379:Prognosis; D012308:Risk Management