title: Predictors of disease recurrence following neoadjuvant chemoradiotherapy and liver transplantation for unresectable perihilar cholangiocarcinoma.
abstract: BACKGROUND
  Sixty-five patients with unresectable hilar cholangiocarcinoma (CCA) have undergone orthotopic liver transplantation (OLT) after neoadjuvant chemoradiotherapy per a clinical care protocol developed in 1993. We reviewed our experience with the aim to identify clinicopathological predictors of disease recurrence.
  
  
  METHODS
  All patients with CCA that underwent OLT at our institution between 1993 and January 1, 2006 were treated in accord with our published protocol. We analyzed multiple clinical and explant pathologic factors using Cox regression analysis.
  
  
  RESULTS
  Sixty-five patients with CCA underwent OLT. Four patients died within six months due to postoperative complications. At last follow-up, 11 patients (17%) had developed recurrence seven to 64 months after OLT. Mean time to recurrence was 29 months, and eight patients had died from recurrent disease. Patient and disease-free survival were 76% and 60% five years after OLT. Predictors of recurrence were older age, pretransplant cancer antigen (CA) 19-9 >100 U/ml, prior cholecystectomy, mass on cross-sectional imaging, residual tumor in explant >2 cm, tumor grade and perineural invasion in explant. Underlying primary sclerosing cholangitis, percutaneous biliary intubation, gender, and other time points for CA 19-9 were not associated with recurrence. Prolonged staging-to-OLT intervals for patients transplanted after implementation of model for end-stage liver disease (MELD) showed a trend toward increased recurrence.
  
  
  CONCLUSIONS
  Older patients and those with high CA-19.9 levels, and larger tumors are more likely to develop recurrent disease. Prolonged waiting time may emerge as a significant risk factor with longer follow-up. These findings may guide patient selection, applicability of live donor transplantation and MELD score exceptions for this aggressive protocol.
authors.affiliation: William J von Liebig Transplant Center, Mayo Clinic College of Medicine, Rochester, MN 55905, USA. heimbach.julie@mayo.edu
authors.forename: Julie K
authors.initials: JK
authors.lastname: Heimbach
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Gores
authors.forename: Michael G
authors.initials: MG
authors.lastname: Haddock
authors.forename: Steven R
authors.initials: SR
authors.lastname: Alberts
authors.forename: Rachel
authors.initials: R
authors.lastname: Pedersen
authors.forename: Walter
authors.initials: W
authors.lastname: Kremers
authors.forename: Scott L
authors.initials: SL
authors.lastname: Nyberg
authors.forename: Michael B
authors.initials: MB
authors.lastname: Ishitani
authors.forename: Charles B
authors.initials: CB
authors.lastname: Rosen
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D001650:Bile Duct Neoplasms / Q000473:pathology / Q000628:therapy*; D001653:Bile Ducts, Intrahepatic / Q000473:pathology; D018395:CA-19-9 Antigen / Q000097:blood*; D018281:Cholangiocarcinoma / Q000473:pathology / Q000628:therapy*; D003131:Combined Modality Therapy; D005260:Female; D006801:Humans; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis* / Q000473:pathology; D011379:Prognosis; D012307:Risk Factors
chemical_list: D018395:CA-19-9 Antigen