title: Association of Histopathologic Phenotype of Periampullary Adenocarcinomas With Survival.
abstract: Patients with periampullary adenocarcinomas have widely variable survival. These cancers are traditionally categorized by their anatomic location of origin, namely, the duodenum, ampulla, distal common bile duct (CBD), or head of the pancreas. However, they can be alternatively subdivided histopathologically into intestinal or pancreaticobiliary (PB) types, which may more accurately estimate prognosis.
  
  
  
  To identify factors associated with survival in patients with periampullary adenocarcinomas and to compare survival between those having intestinal-type or PB-type cancers originating from the duodenum, ampulla, or distal CBD with those having pancreatic ductal adenocarcinoma (PDAC).
  
  
  
  This study was a retrospective analysis of medical records in a prospectively maintained database. Three pathologists separately evaluated histopathologic phenotypes at a university-based tertiary referral center. Study participants were all patients (N = 510) who underwent pancreatoduodenectomy for adenocarcinoma between January 1995 and December 2014.
  
  
  
  Overall survival.
  
  
  
  This study identified 510 patients (mean [SD] age, 66.1 [10.9] years; 245 female [48%]) who underwent pancreatoduodenectomy for adenocarcinomas: 13 duodenal, 110 ampullary, 43 distal CBD, and 344 PDAC. The median overall survival was 61.2 (interquartile range [IQR], 22.0-111.0), 70.4 (IQR, 26.7-147.7), 40.6 (IQR, 15.2-59.6), and 31.4 (IQR, 17.3-86.3) months for patients with cancers of the duodenum, ampulla, distal CBD, or pancreas, respectively (P = .01), indicating a significant difference between the 4 tumor anatomic locations. Most duodenal (61.5% [8 of 13]) and ampullary (51.8% [57 of 110]) cancers were intestinal type, and most distal CBD tumors were PB type (86.0% [37 of 43]). Those with intestinal-type duodenal, ampullary, or distal CBD adenocarcinomas had longer median overall survival than those with PB type (71.7 vs 33.3 months, P = .02) or PDAC (31.4 months, P = .003). There was no survival difference between PB-type cancers and PDAC (33.3 vs 31.4 months, P = .66). On multivariable analysis, histologic grade (hazard ratio [HR], 1.98; 95% CI, 1.56-2.52; P < .001), histopathologic phenotype (HR, 1.75; 95% CI, 1.16-2.64; P = .008), and nodal status (HR, 1.45; 95% CI, 1.12-1.87; P = .05) were significantly associated with survival, while anatomic location was not.
  
  
  
  Histopathologic phenotype is a better prognosticator of survival in patients with periampullary adenocarcinomas than tumor anatomic location. Those with PB-type duodenal, ampullary, or distal CBD adenocarcinomas have survival similar to those with PDAC.
authors.affiliation: Department of Surgery, Harbor-UCLA Medical Center, Los Angeles, California2Department of Surgery, David Geffen School of Medicine, University of California, Los Angeles.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Williams
authors.affiliation: Department of Surgery, David Geffen School of Medicine, University of California, Los Angeles.
authors.forename: Carmen K
authors.initials: CK
authors.lastname: Chan
authors.affiliation: Department of Surgery, David Geffen School of Medicine, University of California, Los Angeles.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Toste
authors.affiliation: Department of Surgery, David Geffen School of Medicine, University of California, Los Angeles.
authors.forename: Irmina A
authors.initials: IA
authors.lastname: Elliott
authors.affiliation: Department of Surgery, David Geffen School of Medicine, University of California, Los Angeles.
authors.forename: Charles R
authors.initials: CR
authors.lastname: Vasquez
authors.affiliation: Department of Surgery, David Geffen School of Medicine, University of California, Los Angeles.
authors.forename: Dharma B
authors.initials: DB
authors.lastname: Sunjaya
authors.affiliation: Department of Pathology, University of Utah, Salt Lake City.
authors.forename: Eric A
authors.initials: EA
authors.lastname: Swanson
authors.affiliation: Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, California.
authors.forename: Jamie
authors.initials: J
authors.lastname: Koo
authors.affiliation: Department of Surgery, David Geffen School of Medicine, University of California, Los Angeles.
authors.forename: O Joe
authors.initials: OJ
authors.lastname: Hines
authors.affiliation: Department of Surgery, David Geffen School of Medicine, University of California, Los Angeles.
authors.forename: Howard A
authors.initials: HA
authors.lastname: Reber
authors.affiliation: Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles.
authors.forename: David W
authors.initials: DW
authors.lastname: Dawson
authors.affiliation: Department of Surgery, David Geffen School of Medicine, University of California, Los Angeles6Department of Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles.
authors.forename: Timothy R
authors.initials: TR
authors.lastname: Donahue
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology* / Q000556:secondary / Q000601:surgery; D000368:Aged; D014670:Ampulla of Vater; D021441:Carcinoma, Pancreatic Ductal / Q000473:pathology / Q000556:secondary / Q000601:surgery; D003138:Common Bile Duct Neoplasms / Q000473:pathology* / Q000601:surgery; D004379:Duodenal Neoplasms / Q000473:pathology* / Q000601:surgery; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D010190:Pancreatic Neoplasms / Q000473:pathology* / Q000601:surgery; D016577:Pancreaticoduodenectomy; D010641:Phenotype; D012189:Retrospective Studies; D015996:Survival Rate