The authors present the results of accuracy measurements, obtained in both laboratory phantom studies and an in vivo assessment, for a technique of frameless stereotaxy. An instrument holder was developed to facilitate stereotactic guidance and enable introduction of frameless methods to traditional frame-based procedures. The accuracy of frameless stereotaxy was assessed for images acquired using 0.5-tesla or 1.5-tesla magnetic resonance (MR) imaging or 2-mm axial, 3-mm axial, or 3-mm helical computerized tomography (CT) scanning. A clinical series is reported in which biopsy samples were obtained using a frameless stereotactic procedure, and the accuracy of these procedures was assessed using postoperative MR images and image fusion. The overall mean error of phantom frameless stereotaxy was found to be 1.3 mm (standard deviation [SD] 0.6 mm). The mean error for CT-directed frameless stereotaxy was 1.1 mm (SD 0.5 mm) and that for MR image-directed procedures was 1.4 mm (SD 0.7 mm). The CT-guided frameless stereotaxy was significantly more accurate than MR image-directed stereotaxy (p = 0.0001). In addition, 2-mm axial CT-guided stereotaxy was significantly more accurate than 3-mm axial CT-guided stereotaxy (p = 0.025). In the clinical series of 21 frameless stereotactically obtained biopsies, all specimens yielded the appropriate diagnosis and no complications ensued. Early postoperative MR images were obtained in 16 of these cases and displacement of the biopsy site from the intraoperative target was determined by fusion of pre- and postoperative image data sets. The mean in vivo linear error of frameless stereotactic biopsy sampling was 2.3 mm (SD 1.9 mm). The mean in vivo Euclidean error was 4.8 mm (SD 2 mm). The implications of these accuracy measurements and of error in stereotaxy are discussed.

A comparison study is presented, which examines the outcome, complications and cost of stereotactic brain biopsy performed with a frameless versus a frame-based method. The technique of frameless stereotactic biopsy has been shown previously, in both laboratory and in vivo studies, to achieve a level of accuracy at least equal to frame-based biopsy. The investigators have validated the technique in a large clinical series. The frameless and frame-based series were concurrent, comprising 76 and 79 cases, respectively. The frameless stereotactic technique involved standard needle biopsy, targeted by an image-guidance system and directed by a novel rigid adjustable instrument-holder. Frame-based biopsies were performed with the CRW and Leksell systems. There were no significant differences in the demographics, lesion site, size and pathologies between the groups. Operating theatre occupancy and anaesthetic time were both significantly shorter for the frameless series than the frame-based series (p < 0.0001). In addition, the complication rate in the frameless biopsy series was significantly lower than in the frame-based series (p = 0.018). This resulted in lower ITU bed occupancy (p = 0.02), shorter mean hospital stay (p = 0.0013) and significant cost savings (p = 0.0022) for the frameless stereotactic biopsy group, despite the greater use of more expensive MRI in these cases. This comparison study demonstrates that the superior imaging, target visualization and flexibility of the technique of frameless stereotactic biopsy translates into tangible advantages for safety, time and cost when compared with the current gold-standard of frame-based biopsy. The principles are discussed and the authors propose a definition for the term 'frameless stereotaxy'.

Non-tumoural cells within the tumour microenvironment (TME) influence tumour proliferation, invasiveness and angiogenesis. Little is known about TME in pituitary neuroendocrine tumours (PitNETs). We aimed to characterise the role of TME in the aggressive behaviour of PitNETs, focusing on immune cells and cytokines. The cytokine secretome of 16 clinically non-functioning PitNETs (NF-PitNETs) and 8 somatotropinomas was assessed in primary culture using an immunoassay panel with 42 cytokines. This was correlated with macrophage (CD68, HLA-DR, CD163), T-lymphocyte (CD8, CD4, FOXP3), B-lymphocyte (CD20), neutrophil (neutrophil elastase) and endothelial cells (CD31) content, compared to normal pituitaries (NPs, n = 5). In vitro tumour–macrophage interactions were assessed by conditioned medium (CM) of GH3 (pituitary tumour) and RAW264.7 (macrophage) cell lines on morphology, migration/invasion, epithelial-to-mesenchymal transition and cytokine secretion. IL-8, CCL2, CCL3, CCL4, CXCL10, CCL22 and CXCL1 are the main PitNET-derived cytokines. PitNETs with increased macrophage and neutrophil content had higher IL-8, CCL2, CCL3, CCL4 and CXCL1 levels. CD8+ T-lymphocytes were associated to higher CCL2, CCL4 and VEGF-A levels. PitNETs had more macrophages than NPs (p < 0.001), with a 3-fold increased CD163:HLA-DR macrophage ratio. PitNETs contained more CD4+ T-lymphocytes (p = 0.005), but fewer neutrophils (p = 0.047) with a 2-fold decreased CD8:CD4 ratio. NF-PitNETs secreted more cytokines and had 9 times more neutrophils than somatotropinomas (p = 0.002). PitNETs with higher Ki-67 had more FOXP3+ T cells, as well as lower CD68:FOXP3, CD8:CD4 and CD8:FOXP3 ratios. PitNETs with “deleterious immune phenotype” (CD68hiCD4hiFOXP3hiCD20hi) had a Ki-67 ≥ 3%. CD163:HLA-DR macrophage ratio was positively correlated with microvessel density (p = 0.015) and area (p < 0.001). GH3 cell-CM increased macrophage chemotaxis, while macrophage-CM changed morphology, invasion, epithelial-to-mesenchymal transition and secreted cytokines of GH3 cells. PitNETs are characterised by increased CD163:HLA-DR macrophage and reduced CD8:CD4 and CD8:FOXP3 T cell ratios. PitNET-derived chemokines facilitate macrophage, neutrophil and T cell recruitment into the tumours which can determine aggressive behaviour.

This study quantified intraoperative brain distortion, determined the different behavior of tumors in four pathological groups, and identified preoperative predictors of shift with which the reliability of neuronavigation may be estimated.

This true frameless stereotactic biopsy technique was associated with low morbidity and mortality rates and an excellent diagnostic yield, with overall results at least as good as those observed for frame-based stereotaxy. The excellent accuracy results demonstrated previously and statistically significant reductions in operative time, as well as improved image presentation, target selection, and simplicity, support the use of this frameless stereotactic technique in preference to frame-based biopsy techniques.