title: Histologic grade is correlated with outcome after resection of hepatic neuroendocrine neoplasms.
abstract: BACKGROUND
  The behavior of neuroendocrine neoplasms is poorly defined, and predictors of outcome after surgical resection have yet to be identified. Consequently, guidelines for treatment remain unclear. Current pathologic classification systems do not permit meaningful discrimination of hepatic neuroendocrine neoplasms.
  
  
  METHODS
  The authors reviewed prospectively maintained databases from 2 institutions of patients who underwent hepatic resection for neuroendocrine neoplasms between 1990 and 2006. Patient, tumor, and operative characteristics were analyzed to identify factors associated with overall survival, progression-free survival, and symptom control. Hepatic neoplasms were stratified by using a 3-tier pathologic classification system based on the number of mitotic figures and the presence of tumor necrosis that was recently validated for pancreatic neuroendocrine neoplasms.
  
  
  RESULTS
  Seventy patients were identified from the databases. Low-grade, intermediate-grade, and high-grade neoplasms were identified in 53%, 37%, and 10% of patients, respectively. After a median follow-up of 51 months, the median overall survival for all patients was 91 months, and it was 108 months when 7 patients with high-grade neuroendocrine carcinomas were excluded. Progressive disease was eventually observed in 81% of patients, and the median progression-free survival was 17 months. The median time to the onset of symptoms was 39 months for patients who presented with hormonal symptoms and 80 months for all patients. Histologic grade was associated with poorer overall and progression-free survival.
  
  
  CONCLUSIONS
  When performed in a context of aggressive multimodality therapy, long-term outcomes after partial hepatectomy for hepatic neuroendocrine neoplasms were favorable; however, disease progression was eventually observed in the majority of patients. Several oncologic variables were associated with significant differences in survival after resection. A novel pathologic classification system appears to enhance prognostic stratification of patients with hepatic neuroendocrine neoplasms.
authors.affiliation: Section of Surgical Oncology, University of Wisconsin School of Medicine and Public Health, H4/724 Clinical Sciences Center, 600 Highland Avenue, Madison, WI 53792-7375, USA. cho@surgery.wisc.edu <cho@surgery.wisc.edu>
authors.forename: Clifford S
authors.initials: CS
authors.lastname: Cho
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Labow
authors.forename: Laura
authors.initials: L
authors.lastname: Tang
authors.forename: David S
authors.initials: DS
authors.lastname: Klimstra
authors.forename: Agnes G
authors.initials: AG
authors.lastname: Loeffler
authors.forename: Glen E
authors.initials: GE
authors.lastname: Leverson
authors.forename: Yuman
authors.initials: Y
authors.lastname: Fong
authors.forename: William R
authors.initials: WR
authors.lastname: Jarnagin
authors.forename: Michael I
authors.initials: MI
authors.lastname: D'Angelica
authors.forename: Sharon M
authors.initials: SM
authors.lastname: Weber
authors.forename: Leslie H
authors.initials: LH
authors.lastname: Blumgart
authors.forename: Ronald P
authors.initials: RP
authors.lastname: Dematteo
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D005260:Female; D006498:Hepatectomy / Q000379:methods*; D006801:Humans; D008113:Liver Neoplasms / Q000145:classification / Q000473:pathology* / Q000601:surgery*; D008297:Male; D008875:Middle Aged; D018358:Neuroendocrine Tumors / Q000145:classification / Q000473:pathology* / Q000601:surgery*; D011379:Prognosis; D016019:Survival Analysis; D016896:Treatment Outcome