The current status of 5-ALA fluorescence-guided resection of intracranial meningiomas-a critical review

Meningiomas are the second most common primary tumors affecting the central nervous system. Surgical treatment can be curative in case of complete resection. 5-aminolevulinic acid (5-ALA) has been established as an intraoperative tool in malignant glioma surgery. A number of studies have tried to outline the merits of 5-ALA for the resection of intracranial meningiomas. In the present paper, we review the existing literature about the application of 5-ALA as an intraoperative tool for the resection of intracranial meningiomas. PubMed was used as the database for search tasks. We included articles published in English without limitations regarding publication date. Tumor fluorescence can occur in benign meningiomas (WHO grade I) as well as in WHO grade II and WHO grade III meningiomas. Most of the reviewed studies report fluorescence of the main tumor mass with high sensitivity and specificity. However, different parts of the same tumor can present with a different fluorescent pattern (heterogenic fluorescence). Quantitative probe fluorescence can be superior, especially in meningiomas with difficult anatomical accessibility. However, only one study was able to consistently correlate resected tissue with histopathological results and nonspecific fluorescence of healthy brain tissue remains a confounder. The use of 5-ALA as a tool to guide resection of intracranial meningiomas remains experimental, especially in cases with tumor recurrence. The principle of intraoperative fluorescence as a real-time method to achieve complete resection is appealing, but the usefulness of 5-ALA is questionable. 5-ALA in intracranial meningioma surgery should only be used in a protocolled prospective and long-term study

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

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. 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 beta (PDGF-beta), vascular endothelial growth factor alpha (VEGF-alpha), 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. 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. 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

Post-implantation syndrome after frozen elephant trunk is associated with the volume of new-onset aortic thrombus

Background: Post-implantation syndrome (PIS) is defined as non-infectious continuous fever and a concomitant rise in inflammatory markers shortly after endovascular aortic repair. PIS occurrence after hybrid procedures, such as the frozen elephant trunk (FET) technique, has not been adequately investigated. The current study aims to define the incidence of PIS after the FET and to identify possible risk factors associated with its occurrence. Methods: The clinical charts of 59 patients undergoing the FET between February 2015 and April 2020 were reviewed retrospectively. The occurrence of PIS was defined as the presence of fever (>38 degrees C lasting longer than one day during the hospitalisation) and leucocytosis (white blood cell count >12,000/mu L). Patients with concomitant conditions possibly leading to fever and/or leucocytosis were excluded. Beside demographic and procedure-related data, serum/plasma inflammatory markers were evaluated before surgery and daily up to seven days postoperatively. Computed tomography scans (CT) were examined to calculate the volume of pre-existent and new-onset mural thrombus after the FET. Results: Thirty-eight patients met the inclusion criteria. The study cohort was divided into two groups based on the occurrence of PIS (17 cases; 44.7%). Patients with PIS were significantly younger than those without PIS (53.5 +/- 8.9 vs. 62.5 +/- 9.6 years; P=0.005). Female patients were less likely to develop PIS (5.2% vs. 26.3%, P=0.018). Patients with PIS had a higher volume of new-onset thrombus in the postoperative CT (P<0.001). Patients treated for post-dissection aneurysm had, postoperatively, significantly more thrombus material developed in a false lumen (P=0.02). Among the PIS markers, CRP (C-reactive protein) levels on the third postoperative day were independently associated with the volume of new-onset thrombus (P=0.011). After multivariate analysis, the volume of new-onset thrombus (P=0.028) and age (P=0.036) remained the variable associated with a statistically significant increased incidence of PIS. Conclusions: PIS can occur after the frozen elephant trunk procedure. The volume of new-onset thrombus seems to be associated with an increased incidence of PIS. These findings need to be confirmed in larger patient cohorts