The Putative S1PR1 Modulator ACT-209905 Impairs Growth and Migration of Glioblastoma Cells In Vitro.

Glioblastoma (GBM) is still a deadly tumor due to its highly infiltrative growth behavior and its resistance to therapy. Evidence is accumulating that sphingosine-1-phosphate (S1P) acts as an important tumor-promoting molecule that is involved in the activation of the S1P receptor subtype 1 (S1PR1). Therefore, we investigated the effect of ACT-209905 (a putative S1PR1 modulator) on the growth of human (primary cells, LN-18) and murine (GL261) GBM cells. The viability and migration of GBM cells were both reduced by ACT-209905. Furthermore, co-culture with monocytic THP-1 cells or conditioned medium enhanced the viability and migration of GBM cells, suggesting that THP-1 cells secrete factors which stimulate GBM cell growth. ACT-209905 inhibited the THP-1-induced enhancement of GBM cell growth and migration. Immunoblot analyses showed that ACT-209905 reduced the activation of growth-promoting kinases (p38, AKT1 and ERK1/2), whereas THP-1 cells and conditioned medium caused an activation of these kinases. In addition, ACT-209905 diminished the surface expression of pro-migratory molecules and reduced CD62P-positive GBM cells. In contrast, THP-1 cells increased the ICAM-1 and P-Selectin content of GBM cells which was reversed by ACT-209905. In conclusion, our study suggests the role of S1PR1 signaling in the growth of GBM cells and gives a partial explanation for the pro-tumorigenic effects that macrophages might have on GBM cells.

Devitalization of Glioblastoma Cancer Cells by Non-invasive Physical Plasma: Modulation of Proliferative Signalling Cascades.

BACKGROUND/AIM: Glioblastoma (GBM) is the most common and most lethal type of cancer of the central nervous system in adults. Despite aggressive treatment, which is based on surgical resection, if possible, followed by radiation and chemotherapy, a high recurrence rate and therapy resistance is observed. Thus, additional innovative therapies are urgently needed to improve the poor median survival of only 15 months. Treatment of solid tumours with non-invasive physical plasma (NIPP) represents such a novel and innovative anticancer procedure. MATERIALS AND METHODS: In this study, we investigated the effect of NIPP, an ionized argon gas, on the in vitro growth of human GBM cell lines, LN-18 and U-87 MG. Proliferation was measured by live cell count. Subsequently, proliferative factors were analysed at the level of nucleic acids (polymerase chain reaction) and proteins (western blotting). RESULTS: For both GBM lines, a treatment time-dependent decrease in growth was observed compared to controls. Additionally, NIPP treatment resulted in reduced rates of AKT serine/threonine kinase 1 (AKT1) and extracellular-regulated kinase 1/2 ERK1/2 expression, whereas expression of p21, proliferating cell nuclear antigen, and heat-shock proteins 90α and 90ß was not affected. In both cell lines, a strong increase in expression of tumour-suppressive microRNA-1 (miR-1) was detected after exposure to NIPP. CONCLUSION: Our results demonstrated that NIPP is able to efficiently attenuate growth of GBM cells and suggest AKT1, ERK1/2 and miR-1 to be pivotal factors of NIPP-modulated cellular signalling. Translated into the clinical setting, NIPP may represent a promising option for the treatment of GBM.

Immunophenotyping of Circulating and Intratumoral Myeloid and T Cells in Glioblastoma Patients.

Glioblastoma is the most common and lethal primary brain malignancy that almost inevitably recurs as therapy-refractory cancer. While the success of immune checkpoint blockade (ICB) revealed the immense potential of immune-targeted therapies in several types of cancers outside the central nervous system, it failed to show objective responses in glioblastoma patients as of now. The ability of glioblastoma cells to drive multiple modes of T cell dysfunction while exhibiting low-quality neoepitopes, low-mutational load, and poor antigen priming limits anti-tumor immunity and efficacy of antigen-unspecific immunotherapies such as ICB. An in-depth understanding of the GBM immune landscape is essential to delineate and reprogram such immunosuppressive circuits during disease progression. In this view, the present study aimed to characterize the peripheral and intratumoral immune compartments of 35 glioblastoma patients compared to age- and sex-matched healthy control probands, particularly focusing on exhaustion signatures on myeloid and T cell subsets. Compared to healthy control participants, different immune signatures were already found in the peripheral circulation, partially related to the steroid medication the patients received. Intratumoral CD4+ and CD8+ TEM cells (CD62Llow/CD45ROhigh) revealed a high expression of PD1, which was also increased on intratumoral, pro-tumorigenic macrophages/microglia. Histopathological analysis further identified high PSGL-1 expression levels of the latter, which has recently been linked to increased metastasis in melanoma and colon cancer via P-selectin-mediated platelet activation. Overall, the present study comprises immunophenotyping of a patient cohort to give implications for eligible immunotherapeutic targets in neurooncology in the future.

Pineal cysts without hydrocephalus: microsurgical resection via an infratentorial-supracerebellar approach-surgical strategies, complications, and their avoidance.

Indications for surgery of pineal cysts without ventriculomegaly are still under debate. In view of the limited data for pineal cyst resection in the absence of hydrocephalus, and the potential risk of this approach, we have analyzed our patient cohort focusing on strategies to avoid complications according to our experience in a series of 73 pineal cyst patients. From 2003 to 2015, we reviewed our database retrospectively for all patients operated on a pineal cyst. Furthermore, we prospectively collected patients from 2016 to 2020. In summary, 73 patients with a pineal cyst were treated surgically between 2003 and 2020. All patients were operated on via a microscopic supracerebellar-infratentorial (SCIT) approach. The mean follow-up period was 26.6 months (range: 6-139 months). Seventy-three patients underwent surgery for a pineal cyst. An absence of enlarged ventricles was documented in 62 patients (51 female, 11 male, mean age 28.1 (range 4-59) years). Main presenting symptoms included headache, visual disturbances, dizziness/vertigo, nausea/emesis, and sleep disturbances. Complete cyst resection was achieved in 59/62 patients. Fifty-five of 62 (89%) patients improved after surgery with good or even excellent results according to the Chicago Chiari Outcome Scale, with complete or partial resolution of the leading symptoms. Pineal cysts resection might be an indication in certain patients for surgery even in the absence of ventriculomegaly. The high percentage of postoperative resolution of quality-of-life impairing symptoms in our series seems to justify surgery. Preoperatively, other causes of the leading symptoms have to be excluded.

A Conceptual Framework for Inducing T Cell-Mediated Immunity Against Glioblastoma.

Glioblastoma is a highly aggressive brain tumor with limited treatment options. Several major challenges have limited the development of novel therapeutics, including the extensive heterogeneity of tumor cell states within each glioblastoma and the ability of glioma cells to diffusely infiltrate into neighboring healthy brain tissue, including the contralateral hemisphere. A T cell-mediated immune response could deal with these challenges based on the ability of polyclonal T cell populations to recognize diverse tumor antigens and perform surveillance throughout tissues. Here we will discuss the major pathways that inhibit T cell-mediated immunity against glioblastoma, with an emphasis on receptor-ligand systems by which glioma cells and recruited myeloid cells inhibit T cell function. A related challenge is that glioblastomas tend to be poorly infiltrated by T cells, which is not only caused by inhibitory molecular pathways but also currently utilized drugs, in particular high-dose corticosteroids that kill activated, proliferating T cells. We will discuss innovative approaches to induce glioblastoma-directed T cell responses, including neoantigen-based vaccines and sophisticated CAR T cell approaches that can target heterogeneous glioblastoma cell populations. Finally, we will propose a conceptual framework for the future development of T cell-based immunotherapies for glioblastoma.

Purely venous compression in trigeminal neuralgia-can we predict the outcome of surgery.

PURPOSE: Controversies regarding venous compression and trigeminal neuralgia (TN) still exist. The study demonstrates our experience for microvascular decompression (MVD) in TN caused by purely venous compression. The goal was to identify prognostic anatomical or surgical factors that may influence the outcome. METHODS: Between 2004 and 2020, 49 patients were operated with purely venous compression. Average age was 58.4 years. Mean history of TN was 7.8 years. Microsurgical procedures included transposition or separation of the vein, coagulation, and division. Several features have been analyzed with respect to BNI scores. RESULTS: Evaluation on discharge revealed a complete pain relief in 39 (80%), partial improvement in 7 (14%), and no benefit in 3 (6%) patients. Facial hypesthesia was reported by 14 (28.6%) patients. Mean follow-up (FU) was 42.1 months. BNI pain intensity score on FU revealed 71.4% excellent to very good scores (score 1: 32 (65.3%); 2: 3 (6.1%)). BNI facial numbness score 2 could be detected in 13 patients (26.5%) during FU. There was no statistical relationship between immediate pain improvement or BNI pain intensity score on FU with respect to surgical procedure, size of trigeminal cistern, type of venous compression, venous caliber, trigeminal nerve indentation, or neurovascular adherence. BNI facial numbness score was dependent on type of venous compression (p < 0.05). CONCLUSION: We did not find typical anatomical features that could either predict or influence the outcome regarding pain improvement or resolution in any form. Neither classic microvascular decompression (interposition/transposition) nor sacrificing the offending vein made any difference in outcome.

Gas Plasma Exposure of Glioblastoma Is Cytotoxic and Immunomodulatory in Patient-Derived GBM Tissue.

Glioblastoma multiforme (GBM) is the most common primary malignant adult brain tumor. Therapeutic options for glioblastoma are maximal surgical resection, chemotherapy, and radiotherapy. Therapy resistance and tumor recurrence demand, however, new strategies. Several experimental studies have suggested gas plasma technology, a partially ionized gas that generates a potent mixture of reactive oxygen species (ROS), as a future complement to the existing treatment arsenal. However, aspects such as immunomodulation, inflammatory consequences, and feasibility studies using GBM tissue have not been addressed so far. In vitro, gas plasma generated ROS that oxidized cells and led to a treatment time-dependent metabolic activity decline and G2 cell cycle arrest. In addition, peripheral blood-derived monocytes were co-cultured with glioblastoma cells, and immunomodulatory surface expression markers and cytokine release were screened. Gas plasma treatment of either cell type, for instance, decreased the expression of the M2-macrophage marker CD163 and the tolerogenic molecule SIGLEC1 (CD169). In patient-derived GBM tissue samples exposed to the plasma jet kINPen ex vivo, apoptosis was significantly increased. Quantitative chemokine/cytokine release screening revealed gas plasma exposure to significantly decrease 5 out of 11 tested chemokines and cytokines, namely IL-6, TGF-ß, sTREM-2, b-NGF, and TNF-α involved in GBM apoptosis and immunomodulation. In summary, the immuno-modulatory and proapoptotic action shown in this study might be an important step forward to first clinical observational studies on the future discovery of gas plasma technology's potential in neurosurgery and neuro-oncology especially in putative adjuvant or combinatory GBM treatment settings.

Preoperative Thrombocytosis is Not Associated with Overall Survival in 309 Glioblastoma Patients.

BACKGROUND: In recent years, a correlation of thrombocytosis and a worse prognosis was shown for many solid cancers, including glioblastoma multiforme (GBM). METHODS: A retrospective review was performed for all patients with a histologically proven and first-diagnosed GBM between 2005 and 2015 in our department. Clinical and paraclinical parameters were acquired from patient documentation and structured for subsequent data analysis. The association of potential risk factors with overall survival was assessed using the Kaplan-Meier survival analysis and Cox regression. RESULTS: The present study includes 309 patients first diagnosed with primary GBM. Our analyses validate well-known risk factors of a decreased overall survival such as higher patient age, a larger preoperative tumor volume, Karnofsky performance status, extent of resection, tumor localization, and adjuvant treatment. However, no correlation was observed between a preoperative thrombocytosis, the mean platelet volume, leucocyte count, activated partial thromboplastin time (apTT), fibrinogen level, and acetylsalicylic acid 100 co-medication. Patients with preoperative hemoglobin below 7.5 mmol/L had decreased overall survival. CONCLUSION: The present study, enrolling the largest numbers of patients assessing this topic to date, did not find any association between a preoperative thrombocytosis and overall survival in 309 patients with GBM.

PIM1 Inhibition Affects Glioblastoma Stem Cell Behavior and Kills Glioblastoma Stem-like Cells.

Despite comprehensive therapy and extensive research, glioblastoma (GBM) still represents the most aggressive brain tumor in adults. Glioma stem cells (GSCs) are thought to play a major role in tumor progression and resistance of GBM cells to radiochemotherapy. The PIM1 kinase has become a focus in cancer research. We have previously demonstrated that PIM1 is involved in survival of GBM cells and in GBM growth in a mouse model. However, little is known about the importance of PIM1 in cancer stem cells. Here, we report on the role of PIM1 in GBM stem cell behavior and killing. PIM1 inhibition negatively regulates the protein expression of the stem cell markers CD133 and Nestin in GBM cells (LN-18, U-87 MG). In contrast, CD44 and the astrocytic differentiation marker GFAP were up-regulated. Furthermore, PIM1 expression was increased in neurospheres as a model of GBM stem-like cells. Treatment of neurospheres with PIM1 inhibitors (TCS PIM1-1, Quercetagetin, and LY294002) diminished the cell viability associated with reduced DNA synthesis rate, increased caspase 3 activity, decreased PCNA protein expression, and reduced neurosphere formation. Our results indicate that PIM1 affects the glioblastoma stem cell behavior, and its inhibition kills glioblastoma stem-like cells, pointing to PIM1 targeting as a potential anti-glioblastoma therapy.

Benefits of Endoscopic Sheath in Intraventricular Neuroendoscopy: Technical Note.

BACKGROUND: The usefulness of the endoscopic sheath is underreported in the literature. OBJECTIVE AND METHODS: To explain the use of an endoscopic sheath and to highlight its benefits. RESULTS: In addition to protecting the surrounding brain parenchyma when inserting the endoscope, the endoscopic sheath is a very useful tool to retract neurovascular structures, achieve hemostasis, and create adequate working space within narrow ventricles. The sheath can be moved within the ventricular system, and the endoscope can be moved independently within the sheath. These movements represent all the advantages of the endoscopic sheath. CONCLUSIONS: We used an endoscopic sheath in ∼ 300 intraventricular neuroendoscopic procedures and consider the sheath an essential part of a ventriculoscopic system. Proper use of the sheath can help avoid or manage endoscopic complications.

Outcome of Endoscope-Assisted Microvascular Decompression in Patients With Hemifacial Spasm Caused by Severe Indentation of the Brain Stem at the Pontomedullary Sulcus by the Posterior Inferior Cerebellar Artery.

BACKGROUND: Microvascular decompression (MVD) is the most effective treatment option for hemifacial spasm (HFS). However, deeply located forms of compression would require proper identification to allow for adequate decompression. OBJECTIVE: To describe the usefulness of endoscopic visualization in one of the most challenging compression patterns in HFS, where the posterior inferior cerebellar artery (PICA) loop is severely indenting the brain stem at the proximal root exit zone of facial nerve along the pontomedullary sulcus. METHODS: Radiological and operative data were checked for all patients in whom severe indentation of the brainstem by PICA at pontomedullary sulcus was recorded and endoscope-assisted MVD was performed. Clinical correlation and outcome were analyzed. RESULTS: A total of 58 patients with HFS were identified with radiological and surgical evidence proving brainstem indentation at the VII transitional zone. In 31 patients, PICA was the offending vessel to the facial nerve. In 3 patients, the PICA loop was mobilized under visualization of a 45° endoscope. A total of 31 patients had a mean follow-up duration of 52.1 mo. The mean duration between start of complaints and surgery was 7.2 yr. In the last follow-up, all patients had remarkable spasm improvement. A total of 5 patients had more than 90% disappearance of spasms and 26 patients experienced spasm-free outcome. CONCLUSION: Although severe indentation of brain stem implies morphological damage, outcome after MVD is excellent. A 45° endoscope is extremely helpful to identify compression down at the pontomedullary sulcus. Deeply located compression site can easily be missed with microscopic inspection alone.

Inhibitory CD161 receptor identified in glioma-infiltrating T cells by single-cell analysis.

T cells are critical effectors of cancer immunotherapies, but little is known about their gene expression programs in diffuse gliomas. Here, we leverage single-cell RNA sequencing (RNA-seq) to chart the gene expression and clonal landscape of tumor-infiltrating T cells across 31 patients with isocitrate dehydrogenase (IDH) wild-type glioblastoma and IDH mutant glioma. We identify potential effectors of anti-tumor immunity in subsets of T cells that co-express cytotoxic programs and several natural killer (NK) cell genes. Analysis of clonally expanded tumor-infiltrating T cells further identifies the NK gene KLRB1 (encoding CD161) as a candidate inhibitory receptor. Accordingly, genetic inactivation of KLRB1 or antibody-mediated CD161 blockade enhances T cell-mediated killing of glioma cells in vitro and their anti-tumor function in vivo. KLRB1 and its associated transcriptional program are also expressed by substantial T cell populations in other human cancers. Our work provides an atlas of T cells in gliomas and highlights CD161 and other NK cell receptors as immunotherapy targets.

Quality of life and olfactory function after suprasellar craniopharyngioma surgery-a single-center experience comparing transcranial and endoscopic endonasal approaches.

The endoscopic endonasal approach to suprasellar craniopharyngiomas has become popular as alternative to transcranial approaches. However, the literature lacks data regarding quality of life and olfactory function. The assessment of the long-term quality of life and olfactory function of all patients harboring a suprasellar craniopharyngioma who underwent surgery in our department has been done. Patient characteristics and perioperative data were gathered in a prospectively maintained database. At the last follow-up visit, the olfactory function and the quality of life (ASBQ, SNOT-22) as well as visual and pituitary function were assessed. Thirteen and 17 patients underwent surgery via a transcranial (T) and endonasal (E) route, respectively. No differences were seen in ASBQ, SNOT-22, and olfactory function between T and E, but in E were more full-time worker and less obesity. CSF leaks occurred in 15% of T and 29% of E (p = 0.43). Patients from group E had a superior visual outcome which was most pronounced in the visual field. The degree of new anterior and posterior pituitary gland deficiency after surgery and in the follow-up was lower in group E. The general and sinonasal quality of life and the olfactory function are equal in E and T. E is associated with a superior visual outcome, lower rates of diabetes insipidus, and lower rates of obesity, but has a higher risk for postoperative CSF leaks.

Endoscopic bimanual sharp dissection technique for gross-total resection of colloid cysts: technical note.

Neuroendoscopic resection of colloid cysts has gained tremendous popularity over the last 2 decades because of good clinical outcomes and a low complication profile. However, in comparison to microsurgical resections, endoscopic resection has a lower rate of gross-total resection, which leaves the patient at risk for cyst recurrence. At present, there is still ongoing debate as to the best surgical approach for colloid cysts. Endoscopic resection as a technique has to compete with the good outcomes of microsurgical resections with respect to a long-term recurrence-free outcome. It is the authors' belief that gross-total resection should be the aim of endoscopic cyst resection. In this technical note, they describe their surgical technique for achieving safe gross-total resection of colloid cysts by using a ventriculoscopic system. The surgical technique includes a far anterolateral entry point, navigational guidance, bimanual sharp dissection, use of the endoscopic sheath as a retractor, the small-chamber irrigation technique, and the dry-field technique for hemostasis.

GD2 targeting by dinutuximab beta is a promising immunotherapeutic approach against malignant glioma.

PURPOSE: Disialoganglioside GD2 is expressed by glioblastoma multiforme (GBM) cells representing a promising target for anti-GD2 immunotherapeutic approaches. The aim of the present study was to investigate anti-tumor efficacy of the chimeric anti-GD2 antibody (Ab) dinutuximab beta against GBM. METHODS: Expression levels of GD2 and complement regulatory proteins (CRP; CD46, CD55 and CD59) on well-known and newly established primary tumor originated GBM cell lines were analyzed by flow cytometry. Ab-dependent cellular (ADCC) and complement-dependent cytotoxicity (CDC) mediated by dinutuximab beta against GBM cells were determined by a non-radioactive calcein-AM-based assay. RESULTS: Analysis of primary GBM cells revealed a heterogeneous GD2 expression that varied between the cell lines analyzed with higher expression levels in the tumor surface compared to the core originated cells. Both GD2-positive and -negative tumor cells were detected in every cell line analyzed. In contrast to CDC, ADCC mediated by dinutuximab beta was observed against the majority of GBM cells. Importantly, CDC-resistant cells showed high expression of the CRP CD46, CD55 and CD59. CONCLUSION: Our present data show anti-tumor effects mediated by dinutuximab beta against GBM cells providing a rationale for a GD2-directed immunotherapy against GBM. Due to high CRP expression, a combining of GD2-targeting with CRP blockade might be a further treatment option for GBM.

ETV in infancy and childhood below 2 years of age for treatment of hydrocephalus.

PURPOSE: Age and etiology play a crucial role in success of endoscopic third ventriculostomy (ETV) as a treatment of obstructive hydrocephalus. Outcome is worse in infants, and controversies still exist whether ETV is superior to shunt placement. We retrospectively analyzed 70 patients below 2 years from 4 different centers treated with ETV and assessed success. METHODS: Children < 2 years who received an ETV within 1994-2018 were included. Patients were classified according to age and etiology; < 3, 4-12, and 13-24 months, etiologically; aqueductal stenosis, post-hemorrhagic-hydrocephalus (PHH), tumor-related, fourth ventricle outflow obstruction, with Chiari-type II and following CSF infection. We investigated statistically the predictors for ETV success through computing Kaplan-Meier estimates using patient's follow-up time and time to ETV failure. RESULTS: We collected 70 patients. ETV success rate was 41.4%. The highest rate was in tumor-related hydrocephalus and fourth ventricle outlet obstruction (62.5%, 60%) and the lowest rate was in Chiari-type II and following infection (16.7%, 0%). The below 3 months age group showed relatively lower success rate (33.3%) in comparison to older groups which showed similar results (46.4%, 46.6%). Statistically, a previous VP shunt was a predictor for failure (p value < 0.05). CONCLUSION: Factors suggesting a high possibility of failure were age < 3 months and etiology such as Chiari-type II or following infection. Altered CSF dynamics in patients with PHH and under-developed arachnoid villi may play a role in ETV failure. We do not recommend ETV as first line in children < 3 months of age or in case of Chiari II or following infection.

Arachnoid bands and venous compression as rare causes of hemifacial spasm: analysis of etiology in 353 patients.

BACKGROUND: Hemifacial spasm is usually caused by arterial compression at the root exit zone of the facial nerve. However, other etiologies have been reported. The aim of this study was to analyze the frequency of other causes of hemifacial spasm. METHODS: Our prospectively maintained hemifacial spasm database containing all patients who underwent microvascular decompression (MVD) for hemifacial spasm from 2002 to 2018 was reviewed. All offending structures were identified and recorded by the surgeon at the time of surgery. Additionally, the operative videos were analyzed retrospectively. RESULTS: MVD was performed in 353 patients. Arterial compression was the main cause of hemifacial spasm in 341 (96.9%) patients. Combined venous-arterial compression was seen in 7 (2.0%) patients. In one patient, the compression was from a large vein. In two patients, no compression was found. One patient who suffered from Bell's palsy many years previously had severe synkinesis and the other had facial tics. In two patients, the spasm was caused due to strangulation of the facial nerve by arachnoid bands. Long-term follow-up of more than 18 months was available in 249 patients with total resolution or near total resolution of spasms in 89.96% of patients. CONCLUSIONS: In most patients with hemifacial spasm, arterial vessels are involved in compressing the facial nerve. Purely venous compression is rarely encountered. We report for the very first time arachnoid bands strangulating the nerve as a cause for hemifacial spasm without involvement of any vessel.

Neuroblastoma with intracerebral metastases and the need for neurosurgery: a single-center experience.

OBJECTIVE: Intracerebral metastases in neuroblastoma patients are rare, and information about the indication for and the outcome of neurosurgical procedures in this setting is scarce in the literature. The authors' aim in the present study was to report a single-center experience with the neurosurgical treatment of intracerebral metastases in neuroblastoma. METHODS: This study is a retrospective single-center analysis of all neurosurgical strategies used in the treatment of intracerebral metastases in neuroblastoma patients. RESULTS: Between 2009 and 2017, 237 pediatric patients (94 girls, 143 boys) with a mean age of 39 months at diagnosis were treated for neuroblastoma. Five (2.1%) of the 237 patients had a neurosurgical procedure for intracerebral metastases. The metastases occurred a mean of 46 months after initial diagnosis. All of these patients had neuroblastoma stage 4. Indications for surgery were recurrent metastases after initial successful oncological treatment or progression of the metastasis under oncological treatment as well as deterioration of neurological function. Intraoperatively, the tumor usually had a distinguishable dissection plane but was infiltrative to adjacent nerves in some spots. Mean overall survival after the neurosurgical procedure was 22 months. Furthermore, in another 3 patients, a neurosurgical procedure was done for an intracranial but extracerebral metastasis. CONCLUSIONS: Neurosurgical procedures for intracerebral metastases in neuroblastoma patients are rare and were performed in 2.1% of patients in the present study. Intracerebral metastases occurred during disease progression, and the prognosis after surgery was very limited. The main indications for surgery were rapid neurological deterioration or recurrence of the metastasis after initial successful oncological treatment. Intraoperatively, the metastases usually had a distinguishable dissection plane from the normal brain tissue.

The Role of Platelets in Cancer Pathophysiology: Focus on Malignant Glioma.

The link between thrombocytosis and malignancy has been well known for many years and its associations with worse outcomes have been reported mainly for solid tumors. Besides measuring platelet count, it has become popular to assess platelet function in the context of malignant diseases during the last decade. Malignant gliomas differ tremendously from malignancies outside the central nervous system because they virtually never form distant metastases. This review summarizes the current understanding of the platelet-immune cell communication and its potential role in glioma resistance and progression. Particularly, we focus on platelet-derived proinflammatory modulators, such as sphingosine-1-phosphate (S1P). The multifaceted interaction with immune cells puts the platelet into an interesting perspective regarding the recent advances in immunotherapeutic approaches in malignant glioma.