title: Distal Cholangiocarcinoma and Pancreas Adenocarcinoma: Are They Really the Same Disease? A 13-Institution Study from the US Extrahepatic Biliary Malignancy Consortium and the Central Pancreas Consortium.
abstract: BACKGROUND
  Distal cholangiocarcinoma (DC) and pancreatic ductal adenocarcinoma (PDAC) are often managed as 1 entity, yet direct comparisons are lacking. Our aim was to use 2 large multi-institutional databases to assess treatment, pathologic, and survival differences between these diseases.
  
  
  METHODS
  This study included patients with DC and PDAC who underwent curative-intent pancreaticoduodenectomy from 2000 to 2015 at 13 institutions comprising the US Extrahepatic Biliary Malignancy and Central Pancreas Consortiums. Primary endpoint was disease-specific survival (DSS).
  
  
  RESULTS
  Of 1,463 patients, 224 (15%) had DC and 1,239 (85%) had PDAC. Compared with PDAC, DC patients were less likely to be margin-positive (19% vs 25%; p = 0.005), lymph node (LN)-positive (55% vs 69%; p < 0.001), and receive adjuvant therapy (57% vs 71%; p < 0.001). Of DC patients treated with adjuvant therapy, 62% got gemcitabine alone and 16% got gemcitabine/cisplatin. Distal cholangiocarcinoma was associated with improved median DSS (40 months) compared with PDAC (22 months; p < 0.001), which persisted on multivariable analysis (hazard ratio 0.65; 95% CI 0.50 to 0.84; p = 0.001). Lymph node involvement was the only factor independently associated with decreased DSS for both DC and PDAC. The DC/LN-positive patients had similar DSS as PDAC/LN-negative patients (p = 0.74). Adjuvant therapy (chemotherapy ± radiation) was associated with improved median DSS for PDAC/LN-positive patients (21 vs 13 months; p = 0.001), but not for DC patients (38 vs 40 months; p = 0.62), regardless of LN status.
  
  
  CONCLUSIONS
  Distal cholangiocarcinoma and pancreatic ductal adenocarcinoma are distinct entities. Distal cholangiocarcinoma has a favorable prognosis compared with PDAC, yet current adjuvant therapy regimens are only associated with improved survival in PDAC, not DC. Therefore, treatment paradigms used for PDAC should not be extrapolated to DC, despite similar operative approaches, and novel therapies for DC should be explored.
authors.affiliation: Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, Atlanta, GA.
authors.forename: Cecilia G
authors.initials: CG
authors.lastname: Ethun
authors.affiliation: Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, Atlanta, GA.
authors.forename: Alexandra G
authors.initials: AG
authors.lastname: Lopez-Aguiar
authors.affiliation: Division of Surgical Oncology, Department of Surgery, Johns Hopkins University, Baltimore, MD; Division of Surgical Oncology, Department of Surgery, The Ohio State University, Columbus, OH.
authors.forename: Timothy M
authors.initials: TM
authors.lastname: Pawlik
authors.affiliation: Department of Surgery, Stanford University, Stanford, CA.
authors.forename: George
authors.initials: G
authors.lastname: Poultsides
authors.affiliation: Division of Surgical Oncology, Department of Surgery, Vanderbilt University, Nashville, TN.
authors.forename: Kamran
authors.initials: K
authors.lastname: Idrees
authors.affiliation: Department of Surgery, Washington University, St Louis, MO.
authors.forename: Ryan C
authors.initials: RC
authors.lastname: Fields
authors.affiliation: Department of Surgery, University of Wisconsin, Madison, WI.
authors.forename: Sharon M
authors.initials: SM
authors.lastname: Weber
authors.affiliation: Department of Surgery, University of Wisconsin, Madison, WI.
authors.forename: Clifford
authors.initials: C
authors.lastname: Cho
authors.affiliation: Division of Surgical Oncology, Department of Surgery, University of Louisville, Louisville, KY.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Martin
authors.affiliation: Division of Surgical Oncology, Department of Surgery, University of Louisville, Louisville, KY.
authors.forename: Charles R
authors.initials: CR
authors.lastname: Scoggins
authors.affiliation: Department of Surgery, Wake Forest University, Winston-Salem, NC.
authors.forename: Perry
authors.initials: P
authors.lastname: Shen
authors.affiliation: Division of Surgical Oncology, Department of Surgery, The Ohio State University, Columbus, OH.
authors.forename: Carl
authors.initials: C
authors.lastname: Schmidt
authors.affiliation: Department of Surgery, New York University, New York, NY.
authors.forename: Ioannis
authors.initials: I
authors.lastname: Hatzaras
authors.affiliation: Department of Surgery, Northwestern University, Chicago, IL.
authors.forename: David
authors.initials: D
authors.lastname: Bentrem
authors.affiliation: Division of Surgical Oncology, Department of Surgery, University of Cincinnati, Cincinnati, OH.
authors.forename: Syed
authors.initials: S
authors.lastname: Ahmad
authors.affiliation: Division of Surgical Oncology, Department of Surgery, University of Cincinnati, Cincinnati, OH; Department of Surgery, University of Wisconsin, Madison, WI.
authors.forename: Daniel
authors.initials: D
authors.lastname: Abbott
authors.affiliation: Division of Surgical Oncology, Department of Surgery, University of North Carolina, Raleigh, NC.
authors.forename: Hong Jin
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Division of Surgical Oncology, Department of Surgery, Vanderbilt University, Nashville, TN; Division of Surgical Oncology, Department of Surgery, University of Miami, Miami, FL.
authors.forename: Nipun
authors.initials: N
authors.lastname: Merchant
authors.affiliation: Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, Atlanta, GA.
authors.forename: Charles A
authors.initials: CA
authors.lastname: Staley
authors.affiliation: Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, Atlanta, GA.
authors.forename: David A
authors.initials: DA
authors.lastname: Kooby
authors.affiliation: Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, Atlanta, GA. Electronic address: smaithe@emory.edu.
authors.forename: Shishir K
authors.initials: SK
authors.lastname: Maithel
mesh_terms: D000328:Adult; D000368:Aged; D001650:Bile Duct Neoplasms / Q000175:diagnosis* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D021441:Carcinoma, Pancreatic Ductal / Q000175:diagnosis* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D059186:Chemoradiotherapy, Adjuvant; D018281:Cholangiocarcinoma / Q000175:diagnosis* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D003138:Common Bile Duct Neoplasms / Q000175:diagnosis* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D016208:Databases, Factual; D003937:Diagnosis, Differential; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000175:diagnosis* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D016577:Pancreaticoduodenectomy; D012189:Retrospective Studies; D016019:Survival Analysis