title: Disseminated tumor cells in bone marrow and the natural course of resected esophageal cancer.
abstract: OBJECTIVE
  To assess the impact of disseminated tumor cells (DTC) in bone marrow on recurrence and survival in complete resected esophageal cancer (EC).
  
  
  BACKGROUND
  Current modalities to predict tumor recurrence and survival in EC are insufficient. Here, we evaluated in a prospective study the prognostic relevance of DTC in bone marrow for the natural postoperative course of EC.
  
  
  METHODS
  We enrolled 370 consecutive EC patients (1995-2009). All tumors, 189 squamous cell carcinomas and 181 adenocarcinomas, were completely surgically resected (R0), and patients received neither neoadjuvant nor adjuvant therapy. Disseminated tumor cells were detected by an immunocytochemical cytokeratin assay in preoperatively taken bone marrow aspirates. The results were correlated with clinic-pathological parameters and clinical outcome.
  
  
  RESULTS
  Overall 120 (32.4%) patients harbored DTC in their bone marrow. Presence of DTC significantly correlated with aggressive tumor biology as indicated by increased tumor size (P = 0.026), regional (P = 0.002) and distant (P = 0.012) lymph node metastases, and higher relapse rate (P < 0.001, χ test). A gradual decrease in disease-free (P < 0.001) and overall (P < 0.001, log-rank test) survival was observed between DTC-negative and DTC-positive patients and was evident in subgroup analysis stratified for nodal status, lymph node yield, lymph node ratio, and tumor subtypes. Disseminated tumor cells were identified as a strong independent prognosticator of tumor recurrence (hazard ratio [HR] 4.0, 95% confidence interval [CI]: 2.96-5.45, P < 0.001) and overall survival (HR 3.1, 95% CI: 2.37-4.09, P < 0.001, Cox regression analysis).
  
  
  CONCLUSIONS
  The presence of DTC in bone marrow is a strong and independent prognostic factor in patients with resectable EC.
authors.affiliation: Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Martinistrasse, Hamburg, Germany.
authors.forename: Yogesh K
authors.initials: YK
authors.lastname: Vashist
authors.forename: Katharina E
authors.initials: KE
authors.lastname: Effenberger
authors.forename: Eik
authors.initials: E
authors.lastname: Vettorazzi
authors.forename: Sabine
authors.initials: S
authors.lastname: Riethdorf
authors.forename: Emre F
authors.initials: EF
authors.lastname: Yekebas
authors.forename: Jakob R
authors.initials: JR
authors.lastname: Izbicki
authors.forename: Klaus
authors.initials: K
authors.lastname: Pantel
mesh_terms: D000230:Adenocarcinoma / Q000503:physiopathology* / Q000556:secondary / Q000601:surgery; D019046:Bone Marrow Neoplasms / Q000503:physiopathology* / Q000556:secondary; D002294:Carcinoma, Squamous Cell / Q000503:physiopathology* / Q000556:secondary / Q000601:surgery; D018450:Disease Progression; D004938:Esophageal Neoplasms / Q000473:pathology / Q000503:physiopathology* / Q000601:surgery; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local; D009360:Neoplastic Cells, Circulating; D011379:Prognosis; D011446:Prospective Studies; D012307:Risk Factors; D016019:Survival Analysis