The Helmet-Visor Pericranial Flap as a Viable Option for Anterior Cranial Base Reconstruction in Complex Oncologic Cases

Objective: To describe a novel bilaterally pedicled pericranial flap for anterior cranial base reconstruction after removal of complex frontobasal cancers extending to the frontal region, thus precluding the use of standard reconstructive techniques. Methods: In selected oncologic cranial base surgeries, the use of the standard galea frontalis pericranial flap for reconstructive purposes may be precluded by tumor infiltration. In such cases, dura mater reconstruction and exclusion of frontal sinuses from the intracranial space can be performed using a large superficial temporal artery bilaterally pedicled pericranial flap obtained from both temporoparietal regions. Surgical technique, indication, contraindication, complications, and degree of resection are recorded to evaluate the efficacy of this surgical method. Results: A 48-year-old man affected by a recurrence of frontobasal squamous cell carcinoma was surgically treated by combined transcranial and endoscopic endonasal resection. A large pericranial flap pedicled bilaterally on the parietal branches of the superficial temporal artery was obtained, transposed anteriorly, carefully watertight sutured to the dural defect, and used to exclude cranialized frontal sinuses as well. The reconstruction was successful, and the patient was discharged home on the tenth postoperative day without any complications and/or development of cerebrospinal fluid leak. Contrast-enhanced magnetic resonance imaging 3 months after surgery was clear from disease with consolidated surgical outcomes. Conclusions: This novel pericranial flap seems to be easily obtained and effective for anterior cranial base reconstruction when the use of a traditional galea frontalis flap is precluded for oncologic reasons and there are concerns for the possible development of contaminations and cerebrospinal fluid leaks

Comaneci-Assisted Coiling of Wide-Necked Intracranial Aneurysm: A Single-Center Preliminary Experience

Background: Wide-necked aneurysms remain challenging for both coiling and microsurgical clipping. They often require additional techniques to prevent coil prolapse into the parent artery, such as balloon- and stent-assisted coiling. Comaneci is an expandable and removable stent that acts as a bridging device and does not interfere with the blood flow of the parent artery. Methods: We retrospectively reviewed our institutional radiological and clinical chart of patients treated for saccular intracranial aneurysm via endovascular Comaneci-assisted coiling. The aim of the study was to report our preliminary experience in Comaneci-assisted coiling of wide-necked intracranial aneurysms. Results: We included 14 patients in the study. Of these, 11 had a ruptured intracranial aneurysm and were treated with Comaneci-assisted coiling. We registered five minor intraprocedural complications and two intraprocedural failures of the device. At one-year follow-up, a satisfying aneurysm occlusion was observed in 85% of the cases. Conclusions: Though long-term follow-up data and larger case series are needed, this preliminary study showed the feasibility of the Comaneci-assisted coiling method for both ruptured and unruptured wide-neck intracranial aneurysms, with similar occlusion rates as balloon-assisted coiling. However, we registered high incidence of thromboembolic complications; these were probably related to the lack of heparin administration. The main advantageous application of this technique is likely in cases of ruptured intracranial aneurysms, as there is no need for post-procedural antiplatelet therapy

Delineating the Cytogenomic and Epigenomic Landscapes of Glioma Stem Cell Lines

<div><p>Glioblastoma multiforme (GBM), the most common and malignant type of glioma, is characterized by a poor prognosis and the lack of an effective treatment, which are due to a small sub-population of cells with stem-like properties, termed glioma stem cells (GSCs). The term “multiforme” describes the histological features of this tumor, that is, the cellular and morphological heterogeneity. At the molecular level multiple layers of alterations may reflect this heterogeneity providing together the driving force for tumor initiation and development. In order to decipher the common “signature” of the ancestral GSC population, we examined six already characterized GSC lines evaluating their cytogenomic and epigenomic profiles through a multilevel approach (conventional cytogenetic, FISH, aCGH, MeDIP-Chip and functional bioinformatic analysis). We found several canonical cytogenetic alterations associated with GBM and a common minimal deleted region (MDR) at 1p36.31, including CAMTA1 gene, a putative tumor suppressor gene, specific for the GSC population. Therefore, on one hand our data confirm a role of driver mutations for copy number alterations (CNAs) included in the GBM genomic-signature (gain of chromosome 7- EGFR gene, loss of chromosome 13- RB1 gene, loss of chromosome 10-PTEN gene); on the other, it is not obvious that the new identified CNAs are passenger mutations, as they may be necessary for tumor progression specific for the individual patient. Through our approach, we were able to demonstrate that not only individual genes into a pathway can be perturbed through multiple mechanisms and at different levels, but also that different combinations of perturbed genes can incapacitate functional modules within a cellular networks. Therefore, beyond the differences that can create apparent heterogeneity of alterations among GSC lines, there’s a sort of selective force acting on them in order to converge towards the impairment of cell development and differentiation processes. This new overview could have a huge importance in therapy.</p> </div

GSC epigenetic signature.

<p>Epigenetic comparison between GSC, NSC and GBM FFPE tissue methylation profiles. The inner circle shows the 378 shared methylated genes in GSC lines, while the middle circle points out 37/378 genes that were unmethylated in NSC lines. The external circle displays the methylation status in GBM FFPE tissues. Note that 10 of the 37 specifically methylated genes in the GSC lines and unmethylated in foetal NSC lines were unmethylated in GBM FFPE tissues, representing the GSC epigenetic signature. The asterisk identifies 27 “cancer <i>de novo</i> methylated genes” in GSC and GBM FFPE tissues vs. foetal NSCs (see also <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0057462#pone.0057462.s016" target="_blank">Table S9A</a>).</p

Chromosomal aberrations identified in the six GSC lines through QFQ-banding and FISH analysis.

<p>The aberrations identified and/or supported by FISH analysis are marked in red. -: loss of whole chromosome; +: gain of whole chromosome; ++: more than one sovrannumerary copy; –: loss of at least two copies of a chromosome;/: lack of alterations. All the numerical alterations are referred to the modal number of chromosomes for each cell line. Numbers in square brackets refer to percentages of each abnormality. From a minimum of 12 to a maximum of 34 metaphases were evaluated for each GSC line and the analysis was performed on at least 3 different passages.</p

The GSCs’ methylation profiles evidence the functional impairment of cell development and differentiation processes.

<p>(A) Functional annotation analysis of commonly methylated or unmethylated gene promoters in all the three GSC lines (GBM2, G144 and G166), performed using GOstat software. The graph shows the percentage (y-axis) of each category compared to totally annotated genes. (B) Top 10 pathways influenced by DNA methylation pattern in GSCs. A p-value (calculated by the Ingenuity Pathway Analysis, IPA, software) is associated to each pathway; this value represents the probability that such association could have occurred by chance.</p

Methylation profiles.

<p>(A) Frequency of methylation and unmethylation of CGIs for each sample. The methylation status for each chromosome is reported and global genomic methylation percentages are displayed as the mean values of all chromosomes values. GSCs vs. CB660SP *p<0.05, **p<0.01, GSCs vs. GBM FFPE tissues §p<0.01, Chi-square test. Abbreviation: Met, methylation; Unmet, unmethylation. (B) Distribution of methylated and unmethylated CGIs among the different functional genomic regions.</p

Cytogenomic profiles of GSCs.

<p>(A) Frequency of gains and losses of whole chromosomes in the six GSC lines analyzed by QFQ-banding. The frequencies of numerical aberrations specific for each chromosome were calculated from the total of the analyzed metaphases of the six cell lines and represented as mean values. (B) Composite array CGH profiles of GSC lines. (C) Detailed 1p LOH mapping of GSC lines. A common region of LOH was identified in all the six GSC lines, involving D1S214 microsatellite, located at 1p36.31 and highlighted by the square box.</p

Unruptured Aneurysms Italian Study (UAIS) background and method

Treatment of unruptured cerebral aneurysms still represents an unsettled question in neurosurgical and neuroradiological communities. Although nowadays the indication for treatment have become relatively clear, indeed uncertainity remains for what concerns the proper treatment modality (surgical or endovascular) in terms of both the risk and the mid and long-term efficacy of the two procedures. The "Unruptured Aneurysms Italian Study" is a cooperative prospective study which aims to delineate the "State of the Art" in a nation based population. It has been designed: 1) to depict the nationwide modality of treatment of Unruptured Aneurysms, 2) to assess in the most objective way the overall treatment-related mortality and morbidity as well as the surgical and endovascular risk in the respective patient populations (it is not a surgical versus endovascular study) and 3) to asses the efficacy of the different procedures in the mid and long term periods. The study started on June 2003 and to June 2006, 637 patients have been enrolled. The study will end when the 1000th patient is enrolled