title: Surgical management of hepatic neuroendocrine tumor metastasis: results from an international multi-institutional analysis.
abstract: BACKGROUND
  Management of neuroendocrine tumor liver metastasis (NELM) remains controversial, with some advocating an aggressive surgical approach while others have adopted a more conservative strategy. We sought to define the efficacy of the surgical management of NELM in a large multicenter international cohort of patients.
  
  
  METHODS
  We identified 339 patients who underwent surgical management for NELM from 1985 to 2009 from an international database of eight major hepatobiliary centers. Relevant clinicopathologic data were assessed using Kaplan-Meier and Cox regression models.
  
  
  RESULTS
  Most patients had a pancreatic (40%) or small bowel (25%) neuroendocrine tumor (NET) primary. The majority of patients (60%) had bilateral liver disease. At surgery, 78% of patients underwent hepatic resection, 3% ablation alone, and 19% resection + ablation. Major hepatectomy was performed in 45% of patients, and 14% underwent a second liver operation. Carcinoid was the most common NET histological subtype (53%). Median survival was 125 months, with overall 5- and 10-year survival of 74%, and 51%, respectively. Disease recurred in 94% of patients at 5 years. Patients with hormonally functional NET who had R0/R1 resection benefited the most from surgery (P = 0.01). On multivariate analyses, synchronous disease [hazard ratio (HR) = 1.9], nonfunctional NET hormonal status (HR = 2.0), and extrahepatic disease (HR = 3.0) remained predictive of worse survival (all P < 0.05).
  
  
  CONCLUSIONS
  Liver-directed surgery for NELM is associated with prolonged survival; however, the majority of patients will develop recurrent disease. Patients with hormonally functional hepatic metastasis without prior extrahepatic or synchronous disease derive the greatest survival benefit from surgical management.
authors.affiliation: Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Skye C
authors.initials: SC
authors.lastname: Mayo
authors.forename: Mechteld C
authors.initials: MC
authors.lastname: de Jong
authors.forename: Carlo
authors.initials: C
authors.lastname: Pulitano
authors.forename: Brian M
authors.initials: BM
authors.lastname: Clary
authors.forename: Srinevas K
authors.initials: SK
authors.lastname: Reddy
authors.forename: T Clark
authors.initials: TC
authors.lastname: Gamblin
authors.forename: Scott A
authors.initials: SA
authors.lastname: Celinksi
authors.forename: David A
authors.initials: DA
authors.lastname: Kooby
authors.forename: Charles A
authors.initials: CA
authors.lastname: Staley
authors.forename: Jayme B
authors.initials: JB
authors.lastname: Stokes
authors.forename: Carrie K
authors.initials: CK
authors.lastname: Chu
authors.forename: Alessandro
authors.initials: A
authors.lastname: Ferrero
authors.forename: Richard D
authors.initials: RD
authors.lastname: Schulick
authors.forename: Michael A
authors.initials: MA
authors.lastname: Choti
authors.forename: Giles
authors.initials: G
authors.lastname: Mentha
authors.forename: Jennifer
authors.initials: J
authors.lastname: Strub
authors.forename: Todd W
authors.initials: TW
authors.lastname: Bauer
authors.forename: Reid B
authors.initials: RB
authors.lastname: Adams
authors.forename: Luca
authors.initials: L
authors.lastname: Aldrighetti
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Capussotti
authors.forename: Timothy M
authors.initials: TM
authors.lastname: Pawlik
mesh_terms: D015331:Cohort Studies; D005260:Female; D006498:Hepatectomy; D006801:Humans; D007390:International Agencies; D008113:Liver Neoplasms / Q000556:secondary / Q000601:surgery*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D018358:Neuroendocrine Tumors / Q000473:pathology / Q000601:surgery*; D015996:Survival Rate; D016896:Treatment Outcome