Renato Galzio

Endoscopic transnasal approach to the cavernous sinus versus transcranial route: anatomic study.

OBJECTIVE: The aim of the present study was to compare the anatomy of the cavernous sinus via an endoscopic transnasal route with the anatomy of the same region explored by the transcranial route. The purpose was to identify and correlate the corresponding anatomic landmarks both through the endoscopic transnasal transsphenoidal and the microscopic transcranial views. METHODS: Five fresh injected heads (10 specimens) were dissected by the endoscopic transnasal and microsurgical transcranial approaches. A comparison of different microsurgical corridors of the cavernous sinus with the corresponding endoscopic transnasal ones was performed. RESULTS: Through the endoscopic transnasal approach, it is possible to explore only some of the parasellar and middle cranial fossa subregions. Because of the complex multilevel architecture of the cavernous sinus, there is not always a correspondence between the surgical corridors bounded through the transcranial route and those exposed through the endoscopic transnasal approach. Nevertheless, some surgical corridors specific to the endoscopic transnasal route are evident: a C-shaped corridor is identifiable medial to the “intracavernous” internal carotid artery, whereas a wider triangular area is delineable lateral to the internal carotid artery; inside the latter, three more surgical corridors (a superior triangular space, a superior quadrangular space, and an inferior quadrangular space) can be described. CONCLUSION: Different surgical corridors can be defined during the endoscopic transnasal approach to the anteroinferior portion of the cavernous sinus, as already established for the transcranial route as well. Knowledge of these could be useful in decreasing morbidity and mortality during surgery in this region, these approaches being reserved to experienced transsphenoidal surgeons only.

Deficit of social cognition in subjects with surgically treated frontal lobe lesions and in subjects affected by schizophrenia

The ability of humans to predict and explain other people’s behaviour by attributing independent mental states such as desires and beliefs to them, is considered to be due to our ability to construct a “Theory of Mind”. Recently, several neuroimaging studies have implicated the medial frontal lobes as playing a critical role in a dedicated “mentalizing” or “Theory of Mind” network in the human brain. In this study we compare the performance of patients with right and left medial prefrontal lobe lesions in theory of mind and in social cognition tasks, with the performance of people with schizophrenia.We report a similar social cognitive profile between patients with prefrontal lobe lesions and schizophrenic subjects in terms of understanding of false beliefs, in understanding social situations and in using tactical strategies. These findings are relevant for the functional anatomy of “Theory of Mind”.

Hypoxia induces peroxisome proliferator-activated receptor α (PPARα) and lipid metabolism peroxisomal enzymes in human glioblastoma cells.

Glioblastoma multiforme (GBM) represents the most severe type of glioma, the most common brain tumor. Their malignancy shows a relationship with an increased proliferation and a poorly organized tumor vascularization, an event that leads to inadequate blood supply, hypoxic areas and at last to the formation of necrotic areas, a feature of glioblastoma. Hypoxic/necrotic tumors are more resistant to chemotherapy and radiation therapies, thus it is crucial to formulate new therapeutic approaches that can render these tumors more sensitive to the action of conventional therapies. It has been demonstrated that under hypoxia, gliomas accumulate lipid droplets and that this event is positively correlated with the degree of malignancy, glioblastoma being the most endowed with lipid droplets. We have previously demonstrated in ex vivo glioma specimens a grade‐dependent lipid metabolism perturbation. Here we studied the lipid pathways and the presence of stemness markers in glioma primary cultures, obtained from surgical specimens of patients affected by glioma at different grade of malignancy, GBM primary cultures cultured under both hypoxic and normoxic conditions, as well as normal human astrocytes. The results obtained demonstrate that hypoxia plays a crucial role in regulating the expression of lipid metabolism peroxisomal enzymes, the lipid droplets accumulation as well as the transcription factor PPARα. J. Cell. Biochem. 112: 3891–3901, 2011.

The interhemispheric transcallosal-transversal approach to the lesions of the anterior and middle third ventricle: Surgical validity and neuropsychological evaluation of the outcome

Based on the observation of the course of callosal fibres and of their artero-venous support as appearing in a microanatomic study, the Authors propose a variant of standard callosotomy procedure by the introduction of the transverse section of callosal fibres. This technique would allow the surgeon to spare a larger number of callosal fibres by the combined effect of a lower direct mechanical traction on fibres and a lower impact on artero-venous microcircle. The neuropsychological outcome of the patients who underwent this kind of procedure was evaluated. Fourteen patients affected by occupying-space lesions involving the anterior and middle third ventricle were included in the study. Ten patients underwent transverse callosotomy, four subjects received standard sagittal callosotomy. A control group was also included in the study. All patients underwent a pre-operative and six months post-operative neuropsychological evaluation focused on performance at cognitive and attentional tasks. No disturbances in executive function were observed in either group. Patients receiving transverse callosotomy performed as well as control group subjects in attentive tasks, which is not the case of patients undergoing sagittal callosotomy who show a marked deficit in selective attention for left side visual field. The observed more favourable neuropsychological outcome supports transverse callosotomy as a valid alternative method to standard longitudinal callosotomy in third ventricle surgery.

Glycosilated nucleolin as marker for human gliomas.

Nucleolin is a multifunctional DNA and RNA binding protein involved in regulation of gene transcription, chromatin remodeling, RNA metabolism, and ribosomal RNA synthesis. Nucleolin seems to be over‐expressed in highly proliferative cells and is involved in many aspect of gene expression: DNA recombination and replication, RNA transcription by RNA polymerase I and II, rRNA processing, mRNA stabilization, cytokinesis, and apoptosis. Although nucleolin is localized predominantly in the nucleolus, it has also been shown to be localized in a phosphorylated/glycolsilated form on the cell surface of different cells. Numerous articles dealing with surface nucleolin targeting for tumor therapy have been recently published. However, at present, no extensive informations are so far available for the presence of nucleolin in human gliomas. In the present work we investigated on the presence and localization of nucleolin in glioma on glioma specimens at different grade of malignancy and on primary glioma cell cultures derived by surgical resection, trying to correlate the presence of glycosilated membrane nucleolin with the malignancy grade. To this purpose an antibody produced by us against gp273 protein, demonstrated to recognized the glycosilated surface nucleolin, has been used. The results obtained demonstrate that surface nucleolin increase with the malignancy grade thus suggesting that it may constitute a histopathological marker for glioma grading and a possible tool for targeted therapy. J. Cell. Biochem. 113: 571–579, 2012.

Cholesterol, cytokines and diseases.

A high level of cholesterol is associated with obesity, cardiovascular diseases and atherosclerosis. Immune response in atherosclerosis is mediated by chemokines which attract monocytes, leading to the innate immune response characterised by the production of cytokines. The immunoregulatory cytokines are an important bridge between innate and adductive immunity. TH1 cytokines are involved as effector T cells in inflammatory response, while TH2 cytokines can be anti-inflammatory such as IL-10 and IL-4. It is well known that statins enhance the production of TH2 cytokines whereas the secretion of TH1 cytokines is suppressed. For this purpose, we studied the significance of anti-inflammatory effect and suppression of inflammation by statins. In this paper we revisited the role of cholesterol and cytokines IL-18, IL-10, IL-12, TNF-α, interferon-γ, and chemokines in inflammatory diseases.

Lipid metabolism impairment in human gliomas: expression of peroxisomal proteins in human gliomas at different grades of malignancy.

Gliomas are histologically graded by cellularity, cytological atypia, necrosis, mitotic figures, and vascular proliferation, features associated with biologically aggressive behaviour. However, abundant evidence suggests the presence of unrecognized, clinically relevant subclasses of the diffuse gliomas, both in respect to their underlying molecular phenotype and their clinical response to therapy. It is well-known that patient prognosis and therapeutic decisions rely on accurate pathological grading. Recently, it was reported that human gliomas accumulate lipid droplets during progression, suggesting a lipid metabolism impairment. Considering the crucial role of peroxisomes in lipid metabolism, in the present work we studied the expression profiles of proteins either exclusively localized to peroxisomes, such as peroxin14 (PEX14), peroxisomal membrane protein 70Kda (PMP70), acyl-CoA oxidase, thiolase, or partially associated to peroxisomes such as Hydroxymethylglutaryl-CoA reductase (HMGCoA-red) and peroxisomal-related proteins, namely PPARa, in human glioma specimens at different grades of malignancy. Moreover, Nile red staining of lipid droplets, thin layer chromatography (TLC) and proton nuclear magnetic resonance spectroscopy (NMR) were carried out in order to correlate the biochemical results with the lipid content of tumor tissues. The results obtained indicate that correlating the malignancy grade with the expression of peroxisomal genes and proteins, may constitute a sensitive tool to highlight possible subtypes not recognized by the classical histological techniques.

Nucleolin antagonist triggers autophagic cell death in human glioblastoma primary cells and decreased in vivo tumor growth in orthotopic brain tumor model

Nucleolin (NCL) is highly expressed in several types of cancer and represents an interesting therapeutic target. It is expressed at the plasma membrane of tumor cells, a property which is being used as a marker for several human cancer including glioblastoma. In this study we investigated targeting NCL as a new therapeutic strategy for the treatment of this pathology. To explore this possibility, we studied the effect of an antagonist of NCL, the multivalent pseudopeptide N6L using primary culture of human glioblastoma cells. In this system, N6L inhibits cell growth with different sensitivity depending to NCL localization. Cell cycle analysis indicated that N6L-induced growth reduction was due to a block of the G1/S transition with down-regulation of the expression of cyclin D1 and B2. By monitoring autophagy markers such as p62 and LC3II, we demonstrate that autophagy is enhanced after N6L treatment. In addition, N6L-treatment of mice bearing tumor decreased in vivo tumor growth in orthotopic brain tumor model and increase mice survival. The results obtained indicated an anti-proliferative and pro-autophagic effect of N6L and point towards its possible use as adjuvant agent to the standard therapeutic protocols presently utilized for glioblastoma.

Laparoscopy-assisted ventriculoperitoneal shunt surgery: personal experience and review of the literature

Ventriculoperitoneal shunting is a widely accepted technique for the treatment of hydrocephalus. The standard procedure to insert the peritoneal catheter requires an abdominal incision, muscle dissection, and opening of the peritoneum. A number of complications related to the abdominal surgical phase have been reported. Laparoscopy-assisted ventriculoperitoneal shunting is a valid alternative procedure that reduces surgical trauma. We describe our experience and review the literature. A total of 30 laparoscopically guided ventriculoperitoneal shunting procedures were performed between January 2007 and June 2008, in collaboration with a general surgeon experienced in laparoscopy. Of these procedures, 25 were new shunt placements and 5 were revisions. Data about operative time, outcome, and complications were registered and compared with a group of 30 patients treated by means of standard laparotomy in the period 2005–2007. Laparoscopic shunt placement was successful in all patients. Operative duration, complications, and postoperative pain were all lower in patients treated by laparoscopy as compared to the laparotomy. In the laparoscopic group, an earlier peristalsis, quicker mobilization, and better cosmetic results were also noted. Laparoscopy in both ventriculoperitoneal shunt placement and revision is a safe, effective, and minimally invasive technique. It ensures proper abdominal placement of the distal catheter under direct vision allowing confirmation of its patency.

The veins of the nucleus dentatus: anatomical and radiological findings.

The veins of the dentate nucleus are composed of several channels draining the external surface and one single vein draining the internal surface. We analyzed specimens of the human cerebellum and described the central vein of the nucleus dentatus as the main venous outflow of the nucleus. The central vein of the nucleus dentatus is formed by a network of smaller vessels draining the sinuosities of the gray matter; it emerges from the hilum of the nucleus and runs along the superior cerebellar peduncle, opening in the anterior vermian vein. We looked for this structure and for the surrounding veins on ultra-high-field (7 Tesla) MR, using susceptibility-weighted imaging. An anatomical and radiological description of the veins of the dentate nucleus is provided, with some remarks on the future clinical applications that these findings could provide.