Alexandros Theodoros Panagopoulos

Expression of cell adhesion proteins and proteins related to angiogenesis and fatty acid metabolism in benign, atypical, and anaplastic meningiomas

Most meningiomas are benign tumours of arachnoidal origin, although a small number have high proliferative rates and invasive properties which complicate complete surgical resection and are associated with increased recurrence rates. Few prognostic indicators exist for meningiomas and further research is necessary to identify factors that influence tumour invasion, oedema and recurrence. Paraffin sections from 25 intracranial meningiomas were analysed for expression of the proteins vascular endothelial growth factor (VEGF), VEGF receptors Flt1 and Flk1, E-cadherin, metalloproteinases 2 and 9 (MMP2, MMP9), CD44, receptor for hyaluronic acid-mediated motility (RHAMM), hyaluronic acid (HA), CD45, cyclooxygenase 2 (COX2), brain fatty acid binding protein (BFABP), Ki67, and proliferating cell nuclear antigen (PCNA). Correlations among protein expression were found for several markers of proliferation (Ki67, PCNA, MI) and microvessel density (MVD). COX2 expression increased with increasing with tumour grade and correlated with Ki67, PCNA, MI, MVD, and BFABP. BFABP expression also correlated with Ki67 and PCNA expression. Relationships were also identified among angiogenic factors (VEGF, Flt1, Flk1) and proliferation markers. Oedema was found to correlate with MMP9 expression and MMP9 also correlated with proliferation markers. No correlations were found for MMP2, E-cadherin, or CD44 in meningiomas. In conclusion Ki67, PCNA, MI, MVD, BFABP, and COX2 were significantly correlated with meningioma tumour grade and with each other. These findings, by correlating both intracellular fatty acid transport and eicosanoid metabolism with tumour proliferation, as determined by Ki67 labelling and mitotic index, suggest fatty acids are involved in the progression of meningiomas.

Petroclival meningiomas: Surgical management and common complications

Petroclival meningiomas are technically challenging lesions. They have a tendency to grow slowly, involve cranial nerves and compress the brainstem and basilar artery, pushing them to the opposite side. Their natural history is marked by clinical deterioration and fatal outcome. They were once considered inoperable lesions; decades ago, mortality rates were higher than 50%. The authors describe 15 petroclival meningiomas treated surgically between 1995 and 2007. The main approaches used were combined anterior petrosectomy and retrosigmoid (3 cases), retrosigmoid (8 cases), and pre-sigmoid and subtemporal (4 cases). The mortality rate was 13.5% due to surgical bed hematoma and brain ischemia. The post-operative complications were hydrocephalus in 2 cases, cerebrospinal fluid leak in 2 cases and infection of surgical flap in one case. Limiting factors for surgical removal are tumor consistency, encasement of brainstem perforators and pre-operative clinical status.

Olfactory groove meningiomas: Approaches and complications

Olfactory groove meningiomas (OGM) account for 4.5% of all intracranial meningiomas. We report 21 patients with OGMs. Tumors were operated on using three surgical approaches: bifrontal (7 patients), fronto-pterional (11 patients) and fronto-orbital (3 patients). Total tumor removal (Simpson Grade 1) was achieved in 13 patients and Simpson II in 8 patients. Perioperative mortality was 4.76%. The average size of the OGM was 4.3+/-1.1cm. The overall recurrence rate was 19%. We preferred to use the pterional approach, which provides quick access to the tumor with less brain exposure. It also allows complete drainage of cisternal cerebrospinal fluid, providing a good level of brain relaxation during surgery. However, for long, thin tumors, hemostasis can be difficult using this approach.

Manejo das neoplasias metastáticas da coluna vertebral - uma atualização

The increased survival of cancer patients due to the improvement and advancement of therapeutic modalities has promoted progressive increase in the prevalence of metastatic tumors of the spine, making it important for healthcare professionals to acquire knowledge in the field. Spinal column metastases are usually secondary to malignant neoplasm of the breast, lung and prostate, male gender being the most often affected and pain being the initial symptom in 90% of patients. It is estimated that 30-90% of terminally ill patients with cancer have metastases at some spinal column segment. Clinical history, physical and neurological assessments are critical to determine the degree and extent of the lesion, and therefore choose the appropriate imaging method to be requested. This study aims to perform a review and didactic description of the main aspects related to the physiopathology, diagnosis and treatment of this disease.

Meningeoma pós-radioterapia

Meningiomas are neoplasms derived from arachnoid cells with their origin linked to idiopathic genetic abnormalities (deletion of the long arm of chromosome 22), predisposing diseases and radiotherapy induction. We report the case of a 50 years-old man radiation-induced meningioma 20 years after the diagnosis, surgical and radiation treatment of an oligodendroglioma. The supporting diagnostic criteria of radiation-induced meningiomas are discussed and the pertinent literature of the theme is revised.

Cryptococcoma mimicking a brain tumor in an immunocompetent patient: case report of an extremely rare presentation

CONTEXT Central nervous system (CNS) infectious diseases have high prevalence in developing countries and their proper diagnosis and treatment are very important for public health planning. Cryptococcus neoformans is a fungus that may cause several CNS manifestations, especially in immunocompromised patients. Cryptococcal meningitis is the most common type of involvement. Mass-effect lesions are uncommon: they are described as cryptococcomas and their prevalence is even lower among immunocompetent patients. The aim here was to report an extremely rare case of cryptococcoma causing a mass effect and mimicking a brain tumor in an immunocompetent patient. The literature on CNS cryptococcal infections was reviewed with emphasis on cryptococcomas. Clinical, surgical and radiological data on a female patient with this rare presentation of cryptococcoma mimicking a brain tumor are described. CASE REPORT A 54-year-old female patient presented to the emergency department with a rapid-onset progressive history of confusion and completely dependency for basic activities. Neuroimaging showed a left occipital lesion and neurosurgical treatment was proposed. From histopathological evaluation, a diagnosis of cryptococcoma was established. She received clinical support with antifungals, but despite optimal clinical treatment, her condition evolved to death. CONCLUSIONS Cryptococcal infections have several forms of presentation and, in immunocompetent patients, their manifestation may be even more different. Cryptococcoma is an extremely rare presentation in which proper surgical and clinical treatment should be instituted as quickly as possible, but even so, there is a high mortality rate.

Cerebellar Liponeurocytoma: A Literature Review and Case Report

Cerebellar liponeurocytoma is an extremely rare cerebellar neoplasm of adults, which is characterized by astrocytic and lipomatous differentiation, with a low proliferative potential. Until now, there are only 31 reports of cerebellar liponeurocytoma. Neurosurgeons are not familiarized with this entity. It is not a part of the tumor repertoire that is dealt with in daily practice. Despite its rarity, it is mandatory to distinguish it from medulloblastomas. Cerebellar liponeurocytoma usually has a more favorable prognosis and does not require chemotherapy or radiotherapy. In this study, we describe a 62-year-old woman harboring cerebellar liponeurocytoma, and briefly review the existing literature.

Opposing roles of PGD2 in GBM

BACKGROUND The World Health Organization classifies glioblastoma (GBM) as a grade IV astrocytoma. Despite the advances in chemotherapy, surgery, and radiation treatments that improve a patients length of survival, the overall trajectory of the disease remains unchanged. GBM cells produce significant levels of various types of bioactive lipids. Prostaglandin D2 (PGD2) influences both pro- and anti-tumorigenic activities in the cell; however, its role in GBM is unclear. Therefore, this study aimed to identify the impact of PGD2 on GBM cell activities in vitro. METHODS First we looked to identify the presence of the PGD2 synthesis pathway through RT-PCR, immunohistochemistry, and HPLC-MS/MS in three GBM cell lines. Then, to observe PGD2s effects on cell count and apoptosis/mitosis (Hoechst 33342 stain), and migration (Transwell Assay), the cells were treated in vitro with physiological (<1μM) and/or supraphysiological (>1μM) concentrations of PGD2 over 72h. HPLC-MS/MS was used to identify the lipid composition of patients with either Grade II/III gliomas or GBM. RESULTS We identified the presence of endogenous PGD2 with its corresponding enzymes and receptors. Exogenous PGD2 both increased cell count (<1μM) and decreased cell count (10μM) in a concentration-dependent manner. There were no significant effects on apoptosis. A significant decrease in mitotic activity was seen only in U251MG, and a significant increase was seen in migration with 5μM PGD2 treatments. A very significant increase of PGD2 was seen from Grade II/III gliomas to GBM. CONCLUSIONS Our study demonstrates that prostaglandin D2 possesses a dynamic, concentration-dependent effect in GBM cell activities. The increase of PGD2 production in GBM patients suggests a pro-tumorigenic role of PGD2 in glioma growth and invasion. Therefore, prostaglandin signaling in GBM requires further investigation to identify new targets for more effective therapies.

The prostanoid pathway contains potential prognostic markers for glioblastoma

Prostanoids derived from the activity of cyclooxygenases and their respective synthases contribute to both active inflammation and immune response in the tumor microenvironment. Their synthesis, deactivation and role in glioma biology have not yet been fully explored and require further study. Using quantitative real time PCR, gas chromatography/ electron impact mass spectrometry and liquid chromatography/ electrospray ionization tandem mass spectrometry, we have further characterized the prostanoid pathway in grade IV glioblastoma (GBM). We observed significant correlations between high mRNA expression levels and poor patient survival for microsomal PGE synthase 1 (mPGES1) and prostaglandin reductase 1 (PTGR1). Conversely, high mRNA expression levels for 15-hydroxyprostaglandin dehydrogenase (15-HPGD) were correlated with better patient survival. GBMs had a higher quantity of the prostanoid precursor, arachidonic acid, versus grade II/III tumors and in GBMs a significant positive correlation was found between arachidonic acid and PGE2 content. GBMs also had higher concentrations of TXB2, PGD2, PGE2 and PGF2α versus grade II/III tumors. A significant decrease in survival was detected for high versus low PGE2, PGE2 + PGE2 deactivation products (PGEMs) and PGF2α in GBM patients. Our data show the potential importance of prostanoid metabolism in the progression towards GBM and provide evidence that higher PGE2 and PGF2α concentrations in the tumor are correlated with poorer patient survival. Our findings highlight the potential importance of the enzymes 15-HPGD and PTGR1 as prognostic biomarkers which could be used to predict survival outcome of patients with GBM.

Feasibility and Limitations of the Retrosigmoid and Presigmoid Approaches Combined With the Anterior Petrosal Approach to Meningiomas in the Petroclival Area

Meningiomas located in the petroclival junction are difficult lesions to manage. Usually, they are diagnosed when they become large-sized symptomatic lesions and extend to adjacent areas. The curative treatment is surgical resection, but the intricate and eloquent neurovascular anatomy of the petroclival complex and adjacent areas challenges the surgeon while considering total tumor resection against the acceptable morbidity and mortality. The authors report 10 case series of tumors arising from or extending to the petroclival junction; they included 10 meningiomas: 4 petroclival, 3 sphenopetroclival, 2 tentorial at the petroclival area, and 1 anterior petrosal operated from 2007 to 2011 in the Hiroshima University Hospital. They were subjected to the combined approaches: anterior petrosal, presigmoid, and retrosigmoid. The translabyrinth approach was added in 2 cases where hearing was previously lost. Gross total resection was possible in 6 cases. The mortality rate was 0. The main complications were postoperative cerebrospinal fluid leak in 1 case, permanent cranial nerve palsy in 3 cases, and venous congestion in 1 case. The main limiting factors for good outcome are the tumor size, wide attachment, hard consistency, bleeding, and preoperative clinical status. Involvement of the basilar artery and perforators, attachment to the brainstem, and avoidance of venous damage are also important points to be considered. As a rule, the anterior petrosal approach yields direct access to the tumor attachment, permitting early devascularization, and direct approach to medial cranial fossa base content. The retrosigmoid is necessary when the tumor is very large and has extended below the internal acoustic meatus. The presigmoid access is useful for cases where the tumors extend to the medial cranial fossa; it reduces the required amount of retraction of the temporal lobe, as it permits the surgeon to change the angle of attack from the lateral to the inferior range.