Relationship between tumor cell infiltration and 5-aminolevulinic acid fluorescence signals after resection of MR-enhancing lesions and its prognostic significance in glioblastoma

Purpose This study investigated the degree of tumor cell infiltration in the tumor cavity and ventricle wall based on fluorescent signals of 5-aminolevulinic acid (5-ALA) after removal of the magnetic resonance (MR)-enhancing area and analyzed its prognostic significance in glioblastoma. Methods Twenty-five newly developed isocitrate dehydrogenase (IDH)-wildtype glioblastomas with complete resection both of MR-enhancing lesions and strong purple fluorescence on resection cavity were retrospectively analyzed. The fluorescent signals of 5-ALA were divided into strong purple, vague pink, and blue colors. The pathologic findings were classified into massively infiltrating tumor cells, infiltrating tumor cells, suspicious single-cell infiltration, and normal-appearing cells. The pathological findings were analyzed according to the fluorescent signals in the resection cavity and ventricle wall. Results There was no correlation between fluorescent signals and infiltrating tumor cells in the resection cavity (p = 0.199) and ventricle wall (p = 0.704) after resection of the MR-enhancing lesion. The median progression-free survival (PFS) and median overall survival (OS) were 12.5 (± 2.1) and 21.1 (± 3.5) months, respectively. In univariate analysis, the presence of definitive infiltrating tumor cells in the resection cavity and ventricle wall was significantly related to the PFS (p = 0.002) and OS (p = 0.027). In multivariate analysis, the absence of definitive infiltrating tumor cells improved PFS (hazard ratio: 0.184; 95% CI: 0.049–0.690, p = 0.012) and OS (hazard ratio: 0.124; 95% CI: 0.015–0.998, p = 0.050). Conclusions After resection both of the MR-enhancing lesions and strong purple fluorescence on resection cavity, there was no correlation between remnant fluorescent signals and infiltrating tumor cells (AU)

Relationship between tumor cell infiltration and 5-aminolevulinic acid fluorescence signals after resection of MR-enhancing lesions and its prognostic significance in glioblastoma.

PURPOSE: This study investigated the degree of tumor cell infiltration in the tumor cavity and ventricle wall based on fluorescent signals of 5-aminolevulinic acid (5-ALA) after removal of the magnetic resonance (MR)-enhancing area and analyzed its prognostic significance in glioblastoma. METHODS: Twenty-five newly developed isocitrate dehydrogenase (IDH)-wildtype glioblastomas with complete resection both of MR-enhancing lesions and strong purple fluorescence on resection cavity were retrospectively analyzed. The fluorescent signals of 5-ALA were divided into strong purple, vague pink, and blue colors. The pathologic findings were classified into massively infiltrating tumor cells, infiltrating tumor cells, suspicious single-cell infiltration, and normal-appearing cells. The pathological findings were analyzed according to the fluorescent signals in the resection cavity and ventricle wall. RESULTS: There was no correlation between fluorescent signals and infiltrating tumor cells in the resection cavity (p = 0.199) and ventricle wall (p = 0.704) after resection of the MR-enhancing lesion. The median progression-free survival (PFS) and median overall survival (OS) were 12.5 (± 2.1) and 21.1 (± 3.5) months, respectively. In univariate analysis, the presence of definitive infiltrating tumor cells in the resection cavity and ventricle wall was significantly related to the PFS (p = 0.002) and OS (p = 0.027). In multivariate analysis, the absence of definitive infiltrating tumor cells improved PFS (hazard ratio: 0.184; 95% CI: 0.049-0.690, p = 0.012) and OS (hazard ratio: 0.124; 95% CI: 0.015-0.998, p = 0.050). CONCLUSIONS: After resection both of the MR-enhancing lesions and strong purple fluorescence on resection cavity, there was no correlation between remnant fluorescent signals and infiltrating tumor cells. The remnant definitive infiltrating tumor cells in the resection cavity and ventricle wall significantly influenced the prognosis of patients with glioblastoma. Aggressive surgical removal of infiltrating tumor cells may improve their prognosis.

Depletion of myeloid-derived suppressor cells during interleukin-12 immunogene therapy does not confer a survival advantage in experimental malignant glioma.

Myeloid-derived suppressor cells (MDSCs) accumulate in the glioma microenvironment during tumor progression and promote immunosuppression. Interleukin-12 (IL-12) immunogene therapy can alter MDSCs toward an antigen-presenting cell phenotype and these mature cells can have a central role in antigen presentation. It remains unclear, however, how MDSC depletion can affect glioma immunotherapy. In this study, we generated a replication-deficient adenoviral vector, Ad.5/3.cRGD-mIL12p70, that transduces the GL261-based murine glioma cell line, resulting in the induction of biologically active, murine IL12p70 expression. Ex vivo, IL-12 expressed by GL261 cells induced interferon-γ synthesis in CD8(+) T cells (P<0.001), CD4(+) T cells (P=0.009) and natural killer cells (P=0.036). When injected 1 week after tumor implantation, Ad.5/3.cRGD-mIL12p70 successfully prolonged the survival of glioma-bearing mice. Sixty percent of animals treated with IL-12 immunotherapy were long-term survivors over 175 days, whereas all the control group animals expired by 40 days after tumor implantation (P=0.026). Mice receiving Ad.5/3.cRGD-mIL12p70 also accumulated 50% less MDSCs in the brain than the control group (P=0.007). Moreover, in the IL-12 group, MDSCs significantly overexpressed CD80 and major histocompatibility complex class II molecules (P=0.041). Depletion of MDSCs with Gr1(+) antibody had no survival benefit induced by IL-12-mediated immunotherapy. Of note, IL-12 therapy increased the presence of myeloid dendritic cells (mDCs) in the glioma microenvironment (P=0.0069). Ultimately, the data show that in the context of IL-12 immunogene therapy, MDSCs are dispensable and mDCs may provide the majority of antigen presentation in the brain.

A molecular dynamics study of the interaction of oleate and dodecylammonium chloride surfactants with complex aluminosilicate minerals.

Surface characteristics of complex aluminosilicate minerals like spodumene [LiAl(SiO(3))(2)], jadeite [NaAl(SiO(3))(2)], feldspar [KAlSi(3)O(8)], and muscovite [K(2)Al(4)(Al(2)Si(6)O(20))(OH)(4)]) are modeled. Surface energies are computed for the cleavage planes of these minerals. Adsorption mechanisms of anionic chemisorbing type oleate and cationic physisorbing type dodecylammonium chloride molecules on two different crystal planes, that is (110) and (001), of spodumene and jadeite are studied in terms of the surface-surfactant interaction energies computed using molecular dynamics (MD) simulations. The conclusions drawn from purely theoretical computations match remarkably well with our experimental results.

De novo appearance of primitive neuroectodermal tumor in a patient with systemic lupus erythematosus and moyamoya disease.

Primitive neuroectodermal tumor is a rare brain tumor composed of undifferentiated or poorly differentiated neuroepithelial cells with a high malignant potential that usually occurs in children, and which is only occasionally encountered in adults. A 19-year-old female with systemic lupus erythematosus presented with right hemiparesis and a headache of 10 days duration. Brain magnetic resonance imaging showed a large solid mass with necrotic portions in the left frontoparietal lobe. Primitive neuroectodermal tumor was confirmed by a neuronavigator-guided brain biopsy. This is the first case report of primitive neuroectodermal tumor associated with systemic lupus erythematosus and moyamoya disease. This case demonstrates that brain tumors, such as primitive neuroectodermal tumor, should be included in the differential diagnosis of neurological manifestations in children and adolescent patients with systemic lupus erythematosus.

Characteristics and management of ruptured distal middle cerebral artery aneurysms.

OBJECTIVE: Distal middle cerebral artery (dMCA) aneurysms are very rare with a reported frequency of 2-6%. Typically, patients with ruptured distal MCA aneurysms have poor clinical outcomes because often there is both a subarachnoid haemorrhage (SAH) and an intracerebral haematoma (ICH). The goals of this study were to identify the characteristics of the distal MCA aneurysms and evaluate the optimal treatment for a good outcome. METHODS: The clinical, neuroradiological and operative records of 8 patients with a ruptured distal MCA aneurysm who underwent surgical management were reviewed retrospectively. The outcomes were presented according to the Glasgow Outcome Scale (GOS). RESULTS: The clinical characteristics of the patients with ruptured dMCA aneurysms included the following: (1) a fusiform appearance in five out of eight (63%) patients. (2) Mean aneurysm size of 9.4 mm (range 2-35 mm). (3) The location being M2 (insular segment) in three, M2-3 junction in three, and M3 (opercular segment) in two patients. (4) Brain CT images revealed both SAH and an ICH in six of eight (75%) patients with the mean size of the ICH being 10 cc (range 5-25 cc). (5) Re-bleeding occurred in four out of eight (50%) of patients. All patients underwent early surgical treatment and the procedures used for surgical repair were, clipping in five patients, trapping in two, and trapping with end-to-end bypass surgery in one patient. Clinical outcomes were poor in two patients (death) due to severe brain swelling. CONCLUSIONS: In this study, dMCA aneurysms had a fusiform shape and a high re-bleeding rate; if ruptured, there was generally ICH and SAH. A good clinical outcome was associated with adequate control of brain swelling and early surgery to prevent re-bleeding.

Clinical utility of multislice computed tomographic angiography for detection of cerebral vasospasm in acute subarachnoid hemorrhage.

Digital subtraction angiography (DSA) has been used as the standard method for detecting cerebral vasospasm after subarachnoid hemorrhage (SAH). Multislice computed tomographic angiography (CTA) is a relatively recent method used for evaluating the vasculature of the intracranial arteries. The purpose of this study was to compare multislice CTA and DSA for the detection and quantification of cerebral vasospasm after SAH, and to analyze the usefulness of multislice CTA. Eight patients with SAH underwent initial CTA with DSA within 72 hours after the onset of symptoms and follow-up multislice CTA and DSA 8 to 48 days after SAH. Five arterial locations were established in the A1 and A2 segments of the anterior cerebral artery, the M1 and M2 segments of the middle cerebral artery and the posterior cerebral artery (PCA) on both multislice CTA and DSA images. Vasospasm was classified as none, mild (up to 30% reduction in luminal diameter), moderate (31-60% reduction), and marked (at least 60% reduction) using the scale of Schneck and Kricheff. The multislice CT system used the following parameters: 1.25 mm collimation and 3.75 pitch with a 4-channel system. The degree of vasospasm revealed by the multislice CTA was significantly correlated with the degree of vasospasm revealed by DSA. In general, most discrepancies between CTA and DSA were in the detection of mild and moderate vasospasm. We found that the consistency between multislice CTA and DSA was greater for mild (100%, n=3) or moderate (100%, n=3) vasospasm than none (n=1) or marked vasospasm (n=1). However, it was unclear whether multislice CTA was more specific for a proximal location (A1, M1, PCA) or distal location (A2, M2) for evaluation of cerebral arteries. Multislice CTA can detect angiographic vasospasm after SAH with an accuracy similar to that of DSA. Multislice CTA is highly sensitive, specific and accurate in detecting mild and moderate cerebral vasospasm. It is less accurate for detecting no vasospasm and marked vasospasm. Therefore, the authors propose that multislice CTA be considered as a useful tool for the detection and management of intracranial vasospasm after SAH.

Neuronavigation-guided endoscopic surgery for pineal tumors with hydrocephalus.

We have applied the neuronavigation system to endoscopic biopsy and third ventriculostomy in the management of patients with a pineal tumor with hydrocephalus. With the guidance of neuronavigation, the two optimal sites of burr hole and trajectories were planned preoperatively, and the advancing endoscopic device was monitored in real time during the procedure. In our five patients, the diameters of the tumors were 2-3 cm, and the mean systemic accuracy of registration with neuronavigation was 1.2 mm. The biopsy and third ventriculostomy were performed successfully via the respective optimal burr hole and the trajectory determined using preoperative neuronavigation. There were no procedure-related complications, and none of the patients needed another procedure for CSF diversion during the follow-up periods. We present our technique which includes the application of the neuronavigation system to the biopsy and third ventriculostomy in pineal tumor with associated hydrocephalus. This technique can be performed using a simple rigid endoscope via the determined optimal entries and trajectories. The optimal preoperative planning and the intraoperative guidance by neuronavigation are thought to be able to give more chances to minimize the brain injury related to movements or deviation of endoscopic device.