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1.  Nonsurgical Strategies in Patients With NET Liver Metastases: A Protocol of Four Systematic Reviews 
JMIR Research Protocols  2014;3(1):e9.
Background
Patients diagnosed with neuroendocrine tumors (NETs) with hepatic metastases generally have a worse prognosis as compared with patients with nonmetastasized NETs. Due to tumor location and distant metastases, a surgical approach is often not possible and nonsurgical therapeutic strategies may apply.
Objective
The aim of these systematic reviews is to evaluate the role of nonsurgical therapy options for patients with nonresectable liver metastases of NETs.
Methods
An objective group of librarians will provide an electronic search strategy to examine the MEDLINE, EMBASE, and The Cochrane Library (Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects, Cochrane Central Register of Controlled Trials [CENTRAL]) databases. 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, 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 four systematic reviews to assess the role of nonsurgical treatment options in patients with neuroendocrine liver metastases.
Conclusions
These systematic reviews, performed according to this protocol, will assess the value of noninvasive therapy options for patients with nonresectable liver metastases of NETs in combination with invasive techniques, such as percutaneous liver-directed techniques and local ablation techniques.
Trial Registration
International Prospective Register of Systematic Reviews (PROSPERO): CRD42012002657; http://www.metaxis.com/PROSPERO/full_doc.asp?RecordID=2657 (Archived by WebCite at http://www.webcitation.org/6NDlYi37O); CRD42012002658; http://www.metaxis.com/PROSPERO/full_doc.asp?RecordID=2658 (Archived by WebCite at http://www.webcitation.org/6NDlfWSuD); CRD42012002659; www.metaxis.com/PROSPERO/full_doc.asp?RecordID=2659 (Arichived by Webcite at http://www.webcitation.org/6NDlmWAFM); and CRD42012002660; http://www.metaxis.com/PROSPERO/full_doc.asp?RecordID=2660 (Archived by WebCite at http://www.webcitation.org/6NDmnylzp).
doi:10.2196/resprot.2893
PMCID: PMC3961806  PMID: 24610518
neuroendocrine tumor; NET; liver resection; adjuvant; neoadjuvant; liver transplantation; primary NET; systematic review
2.  Diagnosis and Prediction of Neuroendocrine Liver Metastases: A Protocol of Six Systematic Reviews 
JMIR Research Protocols  2013;2(2):e60.
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.
Trial Registration
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).
doi:10.2196/resprot.2890
PMCID: PMC3875889  PMID: 24366180
neuroendocrine tumors (NET); liver metastases; Ki67; mitotic count; genetic signatures; tumor cells; biochemical markers; morphological imaging; functional imaging; systematic review
3.  Transplantation and Surgical Strategies in Patients With Neuroendocrine Liver Metastases: Protocol of Four Systematic Reviews 
JMIR Research Protocols  2013;2(2):e58.
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.
Trial Registration
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).
doi:10.2196/resprot.2891
PMCID: PMC3875902  PMID: 24366112
neuroendocrine tumors; NET; liver resection; adjuvant neoadjuvant; liver transplantation; primary NET; systematic review
4.  Pheochromocytoma crisis 
Clinical Case Reports  2013;2(1):14.
Key Clinical Message
Adrenergic crisis induced by a pheochromocytoma leads to life-threatening catecholamine-induced hemodynamic disturbances. Successful treatment of a pheochromocytoma crisis demands prompt diagnosis, vigorous pharmacological therapy and emergent tumor removal, if the patient continues to deteriorate
doi:10.1002/ccr3.6
PMCID: PMC4184766  PMID: 25356229
Critical care medicine; general surgery
5.  The value of pancreatic stone protein in predicting acute appendicitis in patients presenting at the emergency department with abdominal pain 
BMC Gastroenterology  2012;12:154.
Background
Pancreatic Stone Protein (PSP) is a protein naturally produced mainly in the pancreas and the gut. There is evidence from experimental and clinical trials that blood PSP levels rise in the presence of inflammation or infection. However, it is not known whether PSP is superior to other established blood tests (e.g. White Blood Count, Neutrophils or C - reactive protein) in predicting appendicitis in patients presenting with abdominal pain and a clinical suspicion of appendicitis at the emergency room.
Methods/design
The PSP Appendix Trial is a prospective, multi-center, cohort study to assess the value of PSP in the diagnostic workup of acute appendicitis. 245 patients will be prospectively recruited. Interim analysis will be performed once 123 patients are recruited. The primary endpoint of the study concerns the diagnostic accuracy of PSP in predicting acute appendicitis and therefore the evidence of appendicitis on the histopathological specimen after appendectomy.
Discussion
The PSP Appendix Trial is a prospective, multi-center, cohort study to assess the value of PSP in the diagnostic workup of acute appendicitis.
Trial registration
ClinicalTrials.gov: NCT01610193; Institution Ethical Board Approval ID: KEKZH- Nr. 2011–0501
doi:10.1186/1471-230X-12-154
PMCID: PMC3503734  PMID: 23098130
PSP; Pancreatic stone protein; Acute appendicitis; Abdominal pain
6.  In vitro norepinephrine significantly activates isolated platelets from healthy volunteers and critically ill patients following severe traumatic brain injury 
Critical Care  2008;12(3):R80.
Introduction
Norepinephrine, regularly used to increase systemic arterial blood pressure and thus improve cerebral perfusion following severe traumatic brain injury (TBI), may activate platelets. This, in turn, could promote microthrombosis formation and induce additional brain damage.
Methods
The objective of this study was to investigate the influence of norepinephrine on platelets isolated from healthy volunteers and TBI patients during the first two post-traumatic weeks. A total of 18 female and 18 male healthy volunteers of different age groups were recruited, while 11 critically ill TBI patients admitted consecutively to our intensive care unit were studied. Arterial and jugular venous platelets were isolated from norepinephrine-receiving TBI patients; peripheral venous platelets were studied in healthy volunteers. Concentration-dependent functional alterations of isolated platelets were analyzed by flow cytometry, assessing changes in surface P-selectin expression and platelet-derived microparticles before and after in vitro stimulation with norepinephrine ranging from 10 nM to 100 μM. The thrombin receptor-activating peptide (TRAP) served as a positive control.
Results
During the first week following TBI, norepinephrine-mediated stimulation of isolated platelets was significantly reduced compared with volunteers (control). In the second week, the number of P-selectin- and microparticle-positive platelets was significantly decreased by 60% compared with the first week and compared with volunteers. This, however, was associated with a significantly increased susceptibility to norepinephrine-mediated stimulation, exceeding changes observed in volunteers and TBI patients during the first week. This pronounced norepinephrine-induced responsiveness coincided with increased arterio-jugular venous difference in platelets, reflecting intracerebral adherence and signs of cerebral deterioration reflected by elevated intracranial pressure and reduced jugular venous oxygen saturation.
Conclusion
Clinically infused norepinephrine might influence platelets, possibly promoting microthrombosis formation. In vitro stimulation revealed a concentration- and time-dependent differential level of norepinephrine-mediated platelet activation, possibly reflecting changes in receptor expression and function. Whether norepinephrine should be avoided in the second post-traumatic week and whether norepinephrine-stimulated platelets might induce additional brain damage warrant further investigations.
doi:10.1186/cc6931
PMCID: PMC2481479  PMID: 18564410

Results 1-6 (6)