title: Transplantation and surgical strategies in patients with neuroendocrine liver metastases: protocol of four systematic reviews.
abstract: BACKGROUND
  Hepatic metastases of neuroendocrine tumors (NETs) are considered a major prognostic factor associated with significantly reduced survival compared to patients without liver metastases. Several surgical and nonsurgical strategies are present to treat resectable and nonresectable liver metastases, some of which have the potential to cure liver mestatases.
  
  
  OBJECTIVE
  The aims of the four systematic reviews presented in the paper are to determine the effectiveness of liver resection versus nonsurgical treatment of patients with NET liver metastases, to investigate the impact of neoadjuvant and adjuvant treatment options on the tumor-free survival, to assess the role of liver transplantation in patients presenting with unresectable bilateral hepatic metastases, and to evaluate the role of primary tumor resection in presence of unresectable liver metastases.
  
  
  METHODS
  Literature search was performed on Medical Literature Analysis and Retrieval System Online, Excerpta Medica Database, and the Cochrane Library (Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects, and Cochrane Central Register of Controlled Trials). No language restrictions were applied. Randomized controlled trials, prospective and retrospective comparative cohort studies, and case-control studies will be used for the qualitative and quantitative synthesis of the systematic reviews. Case series will be only included in a separate database for descriptive purposes.
  
  
  RESULTS
  This study is ongoing and presents a protocol system of four systematic reviews that will assist in determining the effectiveness of liver resection versus nonsurgical treatment of patients with NET liver metastases. This study is also assumed to investigate the impact of neoadjuvant and adjuvant treatment options on the tumor-free survival, the role of liver transplantation, and the relevance of primary tumor resection in presence of unresectable liver metastasis.
  
  
  CONCLUSIONS
  The systematic reviews will show the current evidence based on the effectiveness of surgical strategies in patients with NET liver metastases and serve as basis for clinical practice guidelines.
  
  
  BACKGROUND
  The systematic reviews have been prospectively registered with the International Prospective Register of Systematic Reviews: liver resection (CRD42012002652); http://www.crd.york.ac.uk/prospero/display_record.asp?ID=CRD42012002652 (Archived by WebCite at http://www.webcitation.org/6LQUqMnqL,). neoadjuvant and adjuvant treatment strategies (CRD42012002656); http://www.crd.york.ac.uk/prospero/display_record.asp?ID=CRD42012002656 (Archived by WebCite at http://www.webcitation.org/6LQVvEHuf). liver transplantation (CRD42012002655); http://www.crd.york.ac.uk/prospero/display_record.asp?ID=CRD42012002655 (Archived by WebCite at http://www.webcitation.org/6LQW7WFo3,). resection of the locoregional primary NET (CRD42012002654); http://www.crd.york.ac.uk/prospero/display_record.asp?ID=CRD42012002654 (Archived by WebCite at http://www.webcitation.org/6LQWEIuGe).
authors.affiliation: Division of Visceral and Transplantation Surgery, Department of Surgery, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Reto
authors.initials: R
authors.lastname: Stump
authors.forename: Silvia
authors.initials: S
authors.lastname: Haueis
authors.forename: Nicola
authors.initials: N
authors.lastname: Kalt
authors.forename: Christoph
authors.initials: C
authors.lastname: Tschuor
authors.forename: Përparim
authors.initials: P
authors.lastname: Limani
authors.forename: Dimitri A
authors.initials: DA
authors.lastname: Raptis
authors.forename: Milo A
authors.initials: MA
authors.lastname: Puhan
authors.forename: Stefan
authors.initials: S
authors.lastname: Breitenstein
keywords: NET; adjuvant neoadjuvant; liver resection; liver transplantation; neuroendocrine tumors; primary NET; systematic review