In patients with a primary NET and synchronous liver metastases, what is the agreement of the biopsy of the primary and the liver metastases with regards to tumour grading?

In patients with metachronous liver metastases, what is the agreement of the biopsy of the primary and the liver metastases with regards to tumour grading?

In patients with liver metastases, what is the agreement of single vs. multiple liver biopsies with regards to tumour grading?

In patients with NET liver metastases, do we need additional biopsies of the normal parenchyma to detect micrometastases?

We will search the following electronic bibliographic databases: MEDLINE, EMBASE and The Cochrane Library (Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects and Cochrane Central Register of Controlled Trials (CENTRAL)). There will be no language restrictions.

Cross-sectional and/or cohort studies.

Neuroendocrine liver metastases.

Inclusion criteria: Patients with primary neuroendocrine tumours and/or liver metastases. Patients who underwent a biopsy of the primary and liver metastasis. Patients who underwent multiple biopsies of the liver metastases and/or healthy parenchyma. Patients aged >=18 years.

Exclusion criteria: Children or adolescents (under the age of 18 years). Studies that do not report histo-pathological biopsy results.

Biopsy(s) of the primary and/or liver metastases.

Tumour grading of the primary vs. the metastasis. Tumour grading among the multiple liver metastases. Tumour grading of the liver metastasis vs. healthy liver parenchyma.

Primary outcomes

Agreement of grading of the primary vs. the metastasis.

Secondary outcomes

Agreement of tumour grading among the multiple liver metastases.

Agreement of tumour grading of the liver metastasis vs. healthy liver parenchyma.

Titles and/or abstracts of studies retrieved using the search strategy will be screened independently by two review team members to identify studies that potentially meet the inclusion criteria outlined above. The full text of these potentially eligible studies will be retrieved and independently assessed for eligibility. Any disagreement over the eligibility of particular studies will be resolved through discussion. A pre-defined protocol will be used to extract data from the included studies for assessment of study quality and evidence synthesis.

To grade the quality (level) of evidence and the strength of recommendations we will use the GRADE (The Grading of Recommendations Assessment, Development and Evaluation, http://www.gradeworkinggroup.org/intro.htm) system to assess the final recommendations.

We will provide a narrative synthesis of the findings from the included studies. A quantitative synthesis will be used if the included studies are sufficiently homogenous. We anticipate that there will be a limited scope for meta-analysis of relatively large number of studies because of the range of different outcomes measured across the small number of existing trials.

None planned

The results of this systematic review will be first presented at the International Consensus Conference on NET Liver Metastases (http://www.netlivermets.com/) and the submitted for consideration for publication at a peer reviewed journal.

Dimitri Raptis

University Hospital Zurich

Department of Surgery

Swiss HPB Center

Raemistrasse 100

CH-8091, Zurich

Switzerland

dimitri.raptis@usz.ch

University Hospital Zurich, Department of Surgery, Swiss HPB Center, Zurich, Switzerland

http://www.en.usz.ch/

Mr Stephan Arigoni, University of Zurich, Switzerland
Mr Stefan Ignjatovic, University of Zurich, Switzerland
Professor Nigel Heaton, King's College Hospital, UK
Dr Laura Tang, Memorial Sloan-Kettering, USA
Dr Ramon Salazar, Institut Catala d Oncologia, Spain
Dr Ashley Grossman, St. Bartholomew's Hospital, London, UK
Professor Cornelis Dejong, Maastricht University Medical Center, The Netherlands
Professor Gregory Gores, Mayo clinic, USA
Milo Puhan, Johns Hopkins Bloomberg School of Public Health, USA
Professor Andrea Frilling, Imperial College London, UK
Professor Mickael Lesurtel, University Hospital Zurich, Switzerland
Dr Dimitri Raptis, University Hospital Zurich, Switzerland
Dr Stefan Breitenstein, University Hospital Zurich, Switzerland

03 March 2012

10 December 2012

University Hospital Zurich, Department of Surgery, Swiss HPB Center, Zurich, Switzerland

None known

English

Switzerland

Subject indexing assigned by CRD

Biopsy; Humans; Liver Neoplasms; Neoplasm Metastasis; Neuroendocrine Tumors

16 July 2012

16 July 2012