title: Diagnosis and prediction of neuroendocrine liver metastases: a protocol of six systematic reviews.
abstract: BACKGROUND
  Patients with hepatic metastases from neuroendocrine tumors (NETs) benefit from an early diagnosis, which is crucial for the optimal therapy and management. Diagnostic procedures include morphological and functional imaging, identification of biomarkers, and biopsy.
  
  
  OBJECTIVE
  The aim of six systematic reviews discussed in this study is to assess the predictive value of Ki67 index and other biomarkers, to compare the diagnostic accuracy of morphological and functional imaging, and to define the role of biopsy in the diagnosis and prediction of neuroendocrine tumor liver metastases.
  
  
  METHODS
  An objective group of librarians will provide an electronic search strategy to examine the following databases: MEDLINE, EMBASE and The Cochrane Library (Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials (CENTRAL), Database of Abstracts of Reviews of Effects). There will be no restriction concerning language and publication date. The qualitative and quantitative synthesis of the systematic review will be conducted with randomized controlled trials (RCT), prospective and retrospective comparative cohort studies, and case-control studies. Case series will be collected in a separate database and only used for descriptive purposes.
  
  
  RESULTS
  This study is ongoing and presents a protocol of six systematic reviews to elucidate the role of histopathological and biochemical markers, biopsies of the primary tumor and the metastases as well as morphological and functional imaging modalities for the diagnosis and prediction of neuroendocrine liver metastases.
  
  
  CONCLUSIONS
  These systematic reviews will assess the value and accuracy of several diagnostic modalities in patients with NET liver metastases, and will provide a basis for the development of clinical practice guidelines.
  
  
  BACKGROUND
  The systematic reviews have been prospectively registered with the International Prospective Register of Systematic Reviews (PROSPERO): CRD42012002644; http://www.metaxis.com/prospero/full_doc.asp?RecordID=2644 (Archived by WebCite at http://www.webcitation.org/6LzCLd5sF), CRD42012002647; http://www.metaxis.com/prospero/full_doc.asp?RecordID=2647 (Archived by WebCite at http://www.webcitation.org/6LzCRnZnO), CRD42012002648; http://www.metaxis.com/prospero/full_doc.asp?RecordID=2648 (Archived by WebCite at http://www.webcitation.org/6LzCVeuVR), CRD42012002649; http://www.metaxis.com/prospero/full_doc.asp?RecordID=2649 (Archived by WebCite at http://www.webcitation.org/6LzCZzZWU), CRD42012002650; http://www.metaxis.com/prospero/full_doc.asp?RecordID=2650 (Archived by WebCite at http://www.webcitation.org/6LzDPhGb8), CRD42012002651; http://www.crd.york.ac.uk/PROSPERO/display_record.asp?ID=CRD42012002651#.UrMglPRDuVo (Archived by WebCite at http://www.webcitation.org/6LzClCNff).
authors.affiliation: Clinic for Visceral and Transplantation Surgery, Department of Surgery, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Stephan
authors.initials: S
authors.lastname: Arigoni
authors.forename: Stefan
authors.initials: S
authors.lastname: Ignjatovic
authors.forename: Patrizia
authors.initials: P
authors.lastname: Sager
authors.forename: Jonas
authors.initials: J
authors.lastname: Betschart
authors.forename: Tobias
authors.initials: T
authors.lastname: Buerge
authors.forename: Josephine
authors.initials: J
authors.lastname: Wachtl
authors.forename: Christoph
authors.initials: C
authors.lastname: Tschuor
authors.forename: Perparim
authors.initials: P
authors.lastname: Limani
authors.forename: Milo A
authors.initials: MA
authors.lastname: Puhan
authors.forename: Mickael
authors.initials: M
authors.lastname: Lesurtel
authors.forename: Dimitri A
authors.initials: DA
authors.lastname: Raptis
authors.forename: Stefan
authors.initials: S
authors.lastname: Breitenstein
keywords: Ki67; biochemical markers; functional imaging; genetic signatures; liver metastases; mitotic count; morphological imaging; neuroendocrine tumors (NET); systematic review; tumor cells