title: Therapy for metastatic pancreatic neuroendocrine tumors.
abstract: BACKGROUND
  Pancreatic neuroendocrine tumors (pNETs) are frequently malignant (50-80%, except for insulinoma) and may show an aggressive course with metastases to the liver as well as more distant sites. These heterogeneous neoplasms include functioning tumors, which secrete a variety of peptide hormones, and non-functioning tumors (up to 90% of pNETs), which often show metastases at the time of diagnosis.
  
  
  METHODS
  A PubMed search was performed for English-language publications from 1995 through December 2012. Reference lists from studies selected were manually searched to identify further relevant reports. Manuscripts comparing different therapeutic options and advances for metastatic pNETs were selected.
  
  
  RESULTS
  The therapeutic options for metastatic pNETs are expanding and include surgery, which remains the only curative approach, liver-directed therapies, and medical therapy. In selected cases also liver transplantation (OLT) may be considered. The option of OLT for metastatic disease is unique to neuroendocrine tumors. Recently, novel promising targeted therapies have been proposed for progressive well-differentiated pNETs.
  
  
  CONCLUSIONS
  The best therapeutic approach for pNETs is still matter of debating. However, since pNETs often show a more indolent behavior compared to other malignancies, the preservation of the quality of life of the patient and the personalization of the therapy according to tumor's and patient's features are mandatory.
authors.affiliation: 1 Gastroenterology Unit II, Fondazione IRCCS Ca' Granda- Ospedale Maggiore Policlinico, Milan, Italy ; 2 Department of Pathophysiology and Transplant, Università degli Studi di Milano, Milan, Italy.
authors.forename: Roberta Elisa
authors.initials: RE
authors.lastname: Rossi
authors.affiliation: 1 Gastroenterology Unit II, Fondazione IRCCS Ca' Granda- Ospedale Maggiore Policlinico, Milan, Italy ; 2 Department of Pathophysiology and Transplant, Università degli Studi di Milano, Milan, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Massironi
authors.affiliation: 1 Gastroenterology Unit II, Fondazione IRCCS Ca' Granda- Ospedale Maggiore Policlinico, Milan, Italy ; 2 Department of Pathophysiology and Transplant, Università degli Studi di Milano, Milan, Italy.
authors.forename: Dario
authors.initials: D
authors.lastname: Conte
authors.affiliation: 1 Gastroenterology Unit II, Fondazione IRCCS Ca' Granda- Ospedale Maggiore Policlinico, Milan, Italy ; 2 Department of Pathophysiology and Transplant, Università degli Studi di Milano, Milan, Italy.
authors.forename: Maddalena
authors.initials: M
authors.lastname: Peracchi
keywords: Pancreatic neuroendocrine tumors (pNETs); duodenocephalopancreasectomy; liver metastases; liver transplantation; liver-directed therapies; somatostatin analogues