title: Primary tumour resection may improve survival in functional well-differentiated neuroendocrine tumours metastatic to the liver.
abstract: BACKGROUND
  Functional well-differentiated neuroendocrine tumours (NET) with liver metastases represent a therapeutic challenge with few alternative options in guidelines. In these patients, the role of surgical resection of the primary tumour is controversial.
  
  
  METHODS
  From a regional registry collecting somatostatin analogue (SSA)-treated tumours from 1979 to 2005, a series of 139 patients presenting with symptomatic, liver-metastatic, well-differentiated NET (G1-G2, mitoses: ≤20, Ki-67: ≤20%) was prospectively collected and retrospectively analysed. Surgery on either the primary tumour or liver metastases was chosen: 1) when low perioperative risk was predictable; 2) in presence of an impending risk of obstruction, bleeding, or perforation; or 3) if liver metastases were suitable of curative or subtotal (>90%) tumour removal. Impact of the most relevant clinico-pathological parameters on survival was studied.
  
  
  RESULTS
  Median follow-up was 127 months and median survival was 94 months, with 138 vs. 37 months in resected vs. non-resected primary NET (p < 0.001), respectively. In the univariate analysis, prolonged survival was significantly associated with primary tumour resection (p < 0.001), resection of liver metastases (p = 0.002), site of primary (carcinoid vs. pancreatic, p = 0.018), basal chromogranin-A (CgA) <200 ng/mL (p = 0.001), and absence of diarrhea (p = 0.012). Multivariate analysis showed that primary tumour resection was an independent positive prognostic factor (HR = 3.17; 95% CI: 1.77-5.69, p < 0.001), whereas diarrhea, basal CgA ≥200 ng/mL, and high tumour load were independent negative prognostic factors. Also, in 103 patients with non-resectable liver metastases, primary tumour resection was significantly associated with prolonged survival (median 137 vs. 32 months, p < 0.0001).
  
  
  CONCLUSIONS
  Primary tumour resection may improve survival in functional well-differentiated NET with liver metastases.
authors.affiliation: Comprehensive ENETS Center, Medical and Surgical Oncology and Pathology, Istituto Nazionale Tumori (National Cancer Institute) IRCCS Foundation, via Venezian 1, 20133 Milan, Italy.
authors.forename: D
authors.initials: D
authors.lastname: Citterio
authors.affiliation: Comprehensive ENETS Center, Medical and Surgical Oncology and Pathology, Istituto Nazionale Tumori (National Cancer Institute) IRCCS Foundation, via Venezian 1, 20133 Milan, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Pusceddu
authors.affiliation: Comprehensive ENETS Center, Medical and Surgical Oncology and Pathology, Istituto Nazionale Tumori (National Cancer Institute) IRCCS Foundation, via Venezian 1, 20133 Milan, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Facciorusso
authors.affiliation: Comprehensive ENETS Center, Medical and Surgical Oncology and Pathology, Istituto Nazionale Tumori (National Cancer Institute) IRCCS Foundation, via Venezian 1, 20133 Milan, Italy.
authors.forename: J
authors.initials: J
authors.lastname: Coppa
authors.affiliation: Comprehensive ENETS Center, Medical and Surgical Oncology and Pathology, Istituto Nazionale Tumori (National Cancer Institute) IRCCS Foundation, via Venezian 1, 20133 Milan, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Milione
authors.affiliation: Comprehensive ENETS Center, Medical and Surgical Oncology and Pathology, Istituto Nazionale Tumori (National Cancer Institute) IRCCS Foundation, via Venezian 1, 20133 Milan, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Buzzoni
authors.affiliation: Comprehensive ENETS Center, Medical and Surgical Oncology and Pathology, Istituto Nazionale Tumori (National Cancer Institute) IRCCS Foundation, via Venezian 1, 20133 Milan, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Bongini
authors.affiliation: Comprehensive ENETS Center, Medical and Surgical Oncology and Pathology, Istituto Nazionale Tumori (National Cancer Institute) IRCCS Foundation, via Venezian 1, 20133 Milan, Italy; University of Milan, Italy.
authors.forename: F
authors.initials: F
authors.lastname: deBraud
authors.affiliation: Comprehensive ENETS Center, Medical and Surgical Oncology and Pathology, Istituto Nazionale Tumori (National Cancer Institute) IRCCS Foundation, via Venezian 1, 20133 Milan, Italy; University of Milan, Italy. Electronic address: vincenzo.mazzaferro@istitutotumori.mi.it.
authors.forename: V
authors.initials: V
authors.lastname: Mazzaferro
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008113:Liver Neoplasms / Q000556:secondary* / Q000601:surgery*; D008875:Middle Aged; D018358:Neuroendocrine Tumors / Q000188:drug therapy / Q000473:pathology* / Q000601:surgery*; D011379:Prognosis; D012042:Registries; D012189:Retrospective Studies; D013004:Somatostatin / Q000031:analogs & derivatives; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D013004:Somatostatin
keywords: Carcinoid tumour; Liver metastases; Neuroendocrine tumours; Prognosis; Somatostatin analogues; Surgical treatment