SSTR-2 as a potential tumour-specific marker for fluorescence-guided meningioma surgery.

BACKGROUND: Meningiomas are the most frequently occurring primary intracranial tumours in adults. Surgical removal can only be curative by complete resection; however surgical access can be challenging due to anatomical localization and local invasion of bone and soft tissues. Several intraoperative techniques have been tried to improve surgical resection, including intraoperative fluorescence guided imaging; however, no meningioma-specific (fluorescent) targeting has been developed yet. Here, we aimed to identify the most promising biomarkers for targeted intra-operative fluorescence guided meningioma surgery. METHODS: One hundred forty-eight meningioma specimens representing all meningioma grades were analysed using immunohistochemistry (IHC) on tissue microarrays (TMAs) to determine expression patterns of meningioma biomarkers epithelial membrane antigen (EMA), platelet-derived growth factor ß (PDGF-ß), vascular endothelial growth factor α (VEGF-α), and somatostatin receptor type 2 (SSTR-2). Subsequently, the most promising biomarker was selected based on TArget Selection Criteria (TASC). Marker expression was examined by IHC in 3D cell culture models generated from freshly resected tumour material. RESULTS: TMA-IHC showed strongest staining for SSTR-2. All cases were positive, with 51.4% strong/diffuse, 30.4% moderate/diffuse and only 18.2% focal/weak staining patterns. All tested biomarkers showed at least weak positivity in all meningiomas, regardless of WHO grade. TASC analysis showed that SSTR-2 was the most promising target for fluorescence guided imaging, with a total score of 21 (out of 22). SSTR-2 expression was determined on original patient tumours and 3D cultures of three established cultures. CONCLUSIONS: SSTR-2 expression was highly sensitive and specific in all 148 meningiomas, regardless of WHO grade. According to TASC analysis, SSTR-2 is the most promising receptor for meningioma targeting. After establishing in vitro meningioma models, SSTR-2 cell membrane expression was confirmed in two of three meningioma cultures as well. This indicates that specific fluorescence in an experimental setting can be performed for the further development of targeted fluorescence guided meningioma surgery and near-infrared fluorescent tracers targeting SSTR-2.

Review on pharmacological pain management in trauma patients in (pre-hospital) emergency medicine in the Netherlands.

Pain is one of the main complaints of trauma patients in (pre-hospital) emergency medicine. Significant deficiencies in pain management in emergency medicine have been identified. No evidence-based protocols or guidelines have been developed so far, addressing effectiveness and safety issues, taking the specific circumstances of pain management of trauma patients in the chain of emergency care into account. The aim of this systematic review was to identify effective and safe initial pharmacological pain interventions, available in the Netherlands, for trauma patients with acute pain in the chain of emergency care. Up to December 2011, a systematic search strategy was performed with MeSH terms and free text words, using the bibliographic databases CINAHL, PubMed and Embase. Methodological quality of the articles was assessed using standardized evaluation forms. Of a total of 2328 studies, 25 relevant studies were identified. Paracetamol (both orally and intravenously) and intravenous opioids (morphine and fentanyl) proved to be effective. Non-steroidal anti-inflammatory drugs (NSAIDs) showed mixed results and are not recommended for use in pre-hospital ambulance or (helicopter) emergency medical services [(H)EMS]. These results could be used for the development of recommendations on evidence-based pharmacological pain management and an algorithm to support the provision of adequate (pre-hospital) pain management. Future studies should address analgesic effectiveness and safety of various drugs in (pre-hospital) emergency care. Furthermore, potential innovative routes of administration (e.g., intranasal opioids in adults) need further exploration.