title: Resection of the primary pancreatic neuroendocrine tumor in patients with unresectable liver metastases: possible indications for a multimodal approach.
abstract: BACKGROUND
  Pancreatic neuroendocrine tumors (PNETs) present in more than 50% of cases with liver metastases as the only systemic localization. Liver metastases are unresectable in 80% of cases at diagnosis. In the context of a metastatic disease, the benefit of primary tumor removal in terms of survival is controversial.
  
  
  METHODS
  A single-center series of patients with PNETs presenting with synchronous unresectable hepatic metastases and treated within a framework of a multidisciplinary team was analyzed retrospectively to assess the prognostic factors and the potential benefit of primary tumor resection on long-term survival.
  
  
  RESULTS
  At the time of diagnosis, 12 of 43 patients (28%) underwent primary tumor resection. After a median follow-up of 5 years (range, 0.6-14 years), 22 disease-related deaths were observed. The corresponding 5-year survival and median disease-specific duration of survival were 58% and 77 months, respectively. In the operated and nonoperated patients the 5-year disease-specific survival was 82% and 50%, respectively (P = .027). At multivariate analysis, patients with primary tumor removed had an improved survival compared with patients who did not (hazard ratio 0.18; 95% CI 0.05-0.66; P = .010). Other important factors associated with improved survival at multivariate analysis were lesser age, lesser Ki-67 index, and 25% less liver tumor burden.
  
  
  CONCLUSIONS
  In the present series of patients with PNETs and unresectable liver metastases, resection of the primary tumor was associated with an improved survival. This observation suggests that resection of the primary tumor should be part of a global therapeutic strategy and its indication and timing should be discussed within a multidisciplinary team.
authors.affiliation: Division of General and Laparoscopic Surgery, European Institute of Oncology, University of Milano, Italy. Electronic address: emilio.bertani@ieo.it.
authors.forename: Emilio
authors.initials: E
authors.lastname: Bertani
authors.affiliation: GI and Neuroendocrine Tumors Unit, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Fazio
authors.affiliation: Division of Epidemiology and Biostatistics, European Institute of Oncology-Milano, Milan, Italy.
authors.forename: Edoardo
authors.initials: E
authors.lastname: Botteri
authors.affiliation: Division of General and Laparoscopic Surgery, European Institute of Oncology, University of Milano, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Chiappa
authors.affiliation: Pancreas Surgical Unit, Università Politecnica delle Marche, Ancona, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Falconi
authors.affiliation: Division of Nuclear Medicine, European Institute of Oncology-Milano, Milan, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Grana
authors.affiliation: Division of Nuclear Medicine, European Institute of Oncology-Milano, Milan, Italy.
authors.forename: Lisa
authors.initials: L
authors.lastname: Bodei
authors.affiliation: Division of General and Laparoscopic Surgery, European Institute of Oncology, University of Milano, Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Papis
authors.affiliation: GI and Neuroendocrine Tumors Unit, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Spada
authors.affiliation: Division of Epidemiology and Biostatistics, European Institute of Oncology-Milano, Milan, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Bazolli
authors.affiliation: Division of General and Laparoscopic Surgery, European Institute of Oncology, University of Milano, Italy.
authors.forename: Bruno
authors.initials: B
authors.lastname: Andreoni
mesh_terms: D000328:Adult; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008113:Liver Neoplasms / Q000401:mortality / Q000556:secondary*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D018358:Neuroendocrine Tumors / Q000401:mortality / Q000473:pathology / Q000601:surgery*; D010190:Pancreatic Neoplasms / Q000401:mortality / Q000473:pathology / Q000601:surgery*; D011379:Prognosis; D012189:Retrospective Studies; D015996:Survival Rate; D016896:Treatment Outcome