title: Implications of CA19-9 elevation for survival, staging, and treatment sequencing in intrahepatic cholangiocarcinoma: A national cohort analysis.
abstract: BACKGROUND
  Optimal management of patients with intrahepatic cholangiocarcinoma (ICCA) and elevated CA19-9 remains undefined. We hypothesized CA19-9 elevation above normal indicates aggressive biology and that inclusion of CA19-9 would improve staging discrimination.
  
  
  METHODS
  The National Cancer Data Base (NCDB-2010-2012) was reviewed for patients with ICCA and reported CA19-9. Patients were stratified by CA19-9 above/below normal reference range. Unadjusted Kaplan-Meier and adjusted Cox-proportional-hazards analysis of overall survival (OS) were performed.
  
  
  RESULTS
  A total of 2,816 patients were included: 938 (33.3%) normal; 1,878 (66.7%) elevated CA19-9 levels. Demographic/pathologic and chemotherapy/radiation were similar between groups, but patients with elevated CA19-9 had more nodal metastases and less likely to undergo resection. Among elevated-CA19-9 patients, stage-specific survival was decreased in all stages. Resected patients with CA19-9 elevation had similar peri-operative outcomes but decreased long-term survival. In adjusted analysis, CA19-9 elevation independently predicted increased mortality with impact similar to node-positivity, positive-margin resection, and non-receipt of chemotherapy. Proposed staging system including CA19-9 improved survival discrimination over AJCC 7th edition.
  
  
  CONCLUSIONS
  Elevated CA19-9 is an independent risk factor for mortality in ICCA similar in impact to nodal metastases and positive resection margins. Inclusion of CA19-9 in a proposed staging system increases discrimination. Multi-disciplinary therapy should be considered in patients with ICCA and CA19-9 elevation. J. Surg. Oncol. 2016;114:475-482. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Section of Hepatobiliary and Pancreatic Surgery, Division of Subspecialty General Surgery, Department of Surgery, Mayo Clinic, Rochester, Minnesota.|Robert D. and Patricia E. Kern Center for the Science of Healthcare Delivery, Mayo Clinic, Rochester, Minnesota.
authors.forename: John R
authors.initials: JR
authors.lastname: Bergquist
authors.affiliation: Section of Hepatobiliary and Pancreatic Surgery, Division of Subspecialty General Surgery, Department of Surgery, Mayo Clinic, Rochester, Minnesota.|Robert D. and Patricia E. Kern Center for the Science of Healthcare Delivery, Mayo Clinic, Rochester, Minnesota.
authors.forename: Tommy
authors.initials: T
authors.lastname: Ivanics
authors.affiliation: Robert D. and Patricia E. Kern Center for the Science of Healthcare Delivery, Mayo Clinic, Rochester, Minnesota.
authors.forename: Curtis B
authors.initials: CB
authors.lastname: Storlie
authors.affiliation: Section of Hepatobiliary and Pancreatic Surgery, Division of Subspecialty General Surgery, Department of Surgery, Mayo Clinic, Rochester, Minnesota.
authors.forename: Ryan T
authors.initials: RT
authors.lastname: Groeschl
authors.affiliation: Section of Hepatobiliary and Pancreatic Surgery, Division of Subspecialty General Surgery, Department of Surgery, Mayo Clinic, Rochester, Minnesota.
authors.forename: May C
authors.initials: MC
authors.lastname: Tee
authors.affiliation: Robert D. and Patricia E. Kern Center for the Science of Healthcare Delivery, Mayo Clinic, Rochester, Minnesota.
authors.forename: Elizabeth B
authors.initials: EB
authors.lastname: Habermann
authors.affiliation: Section of Hepatobiliary and Pancreatic Surgery, Division of Subspecialty General Surgery, Department of Surgery, Mayo Clinic, Rochester, Minnesota.
authors.forename: Rory L
authors.initials: RL
authors.lastname: Smoot
authors.affiliation: Section of Hepatobiliary and Pancreatic Surgery, Division of Subspecialty General Surgery, Department of Surgery, Mayo Clinic, Rochester, Minnesota.
authors.forename: Michael L
authors.initials: ML
authors.lastname: Kendrick
authors.affiliation: Section of Hepatobiliary and Pancreatic Surgery, Division of Subspecialty General Surgery, Department of Surgery, Mayo Clinic, Rochester, Minnesota.
authors.forename: Michael B
authors.initials: MB
authors.lastname: Farnell
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, Minnesota.
authors.forename: Lewis R
authors.initials: LR
authors.lastname: Roberts
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, Minnesota.
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Gores
authors.affiliation: Section of Hepatobiliary and Pancreatic Surgery, Division of Subspecialty General Surgery, Department of Surgery, Mayo Clinic, Rochester, Minnesota.
authors.forename: David M
authors.initials: DM
authors.lastname: Nagorney
authors.affiliation: Section of Hepatobiliary and Pancreatic Surgery, Division of Subspecialty General Surgery, Department of Surgery, Mayo Clinic, Rochester, Minnesota.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Truty
mesh_terms: D000368:Aged; D001650:Bile Duct Neoplasms / Q000097:blood / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D018395:CA-19-9 Antigen / Q000097:blood*; D018281:Cholangiocarcinoma / Q000097:blood / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D016016:Proportional Hazards Models
chemical_list: D018395:CA-19-9 Antigen
keywords: CA19-9; biologic resectability; biomarker; cholangiocarcinoma