title: High-grade pancreatic intraepithelial lesions: prevalence and implications in pancreatic neoplasia.
abstract: BACKGROUND
  High-grade pancreatic intraepithelial neoplasia (PanIN-3), a precursor of pancreatic ductal adenocarcinoma (PDAC), is not universally detected in resected pancreatic neoplasms. We sought to determine the prevalence and prognostic relevance of PanIN-3 lesions in primary surgical resections of PDACs and intraductal papillary mucinous neoplasms (IPMNs).
  
  
  METHODS
  A retrospective review of a tertiary care center pathology database (1/2000-6/2014) was performed. Demographics, imaging, pathology, disease-recurrence, and survival data were reviewed.
  
  
  RESULTS
  A total of 458 patients who underwent primary pancreatic resection were included. "PanIN-3" lesions were found in 74 (16.2%) patients who either had PDAC (n=67) or main duct (MD)-IPMN (n=7). Among IPMN-MDs, PanIN-3 lesions were exclusively found in those with pathological evidence of chronic pancreatitis. For PDACs, the median overall survival (OS) for pancreata with PanIN-3 lesions was significantly better than those without (OS 1.12 years, inter-quartile range [IQR] 0.72, 2.05 years vs OS 0.86 years, IQR 0.64, 1.60 years respectively; P=0.04). Multivariate Cox regression analysis demonstrated that the presence of PanIN-3 lesions was associated with a reduced risk of death (HR=0.43; 95% CI: 0.23-0.82; P=0.01).
  
  
  CONCLUSIONS
  Following primary resection of pancreatic adenocarcinoma, the lower survival observed in patients without PanIN-3 lesions might suggest a state of complete or accelerated transformation. Further investigations are necessary to validate these findings that might impact disease prognosis and management.
authors.affiliation: Division of Hospital Medicine, Division of Gastroenterology, Hepatology and Nutrition, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA. Somashekar_krishna@osumc.edu.
authors.forename: Jean R
authors.initials: JR
authors.lastname: Park
authors.forename: Feng
authors.initials: F
authors.lastname: Li
authors.forename: Veeral M
authors.initials: VM
authors.lastname: Oza
authors.forename: Brett C
authors.initials: BC
authors.lastname: Sklaw
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Cronley
authors.forename: Michael
authors.initials: M
authors.lastname: Wellner
authors.forename: Benjamin
authors.initials: B
authors.lastname: Swanson
authors.forename: Somashekar G
authors.initials: SG
authors.lastname: Krishna
mesh_terms: D000231:Adenocarcinoma, Papillary / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D000368:Aged; D002278:Carcinoma in Situ / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D021441:Carcinoma, Pancreatic Ductal / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D016009:Chi-Square Distribution; D016208:Databases, Factual; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D060787:Neoplasm Grading; D009364:Neoplasm Recurrence, Local; D018297:Neoplasms, Cystic, Mucinous, and Serous / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D009820:Ohio; D010180:Pancreatectomy; D010190:Pancreatic Neoplasms / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D012307:Risk Factors; D062606:Tertiary Care Centers; D013997:Time Factors; D016896:Treatment Outcome