Domenico d’Avella

Hyaluronan and Fibrin Biomaterial as Scaffolds for Neuronal Differentiation of Adult Stem Cells Derived from Adipose Tissue and Skin

Recently, we have described a simple protocol to obtain an enriched culture of adult stem cells organized in neurospheres from two post-natal tissues: skin and adipose tissue. Due to their possible application in neuronal tissue regeneration, here we tested two kinds of scaffold well known in tissue engineering application: hyaluronan based membranes and fibrin-glue meshes. Neurospheres from skin and adipose tissue were seeded onto two scaffold types: hyaluronan based membrane and fibrin-glue meshes. Neurospheres were then induced to acquire a glial and neuronal-like phenotype. Gene expression, morphological feature and chromosomal imbalance (kariotype) were analyzed and compared. Adipose and skin derived neurospheres are able to grow well and to differentiate into glial/neuron cells without any chromosomal imbalance in both scaffolds. Adult cells are able to express typical cell surface markers such as S100; GFAP; nestin; βIII tubulin; CNPase. In summary, we have demonstrated that neurospheres isolated from skin and adipose tissues are able to differentiate in glial/neuron-like cells, without any chromosomal imbalance in two scaffold types, useful for tissue engineering application: hyaluronan based membrane and fibrin-glue meshes.

MGMT expression and promoter methylation status may depend on the site of surgical sample collection within glioblastoma: a possible pitfall in stratification of patients?

We recently described a three-layer concentric model of a glioblastoma (GBM) related to a specific distribution of molecular and phenotypic characteristics driven by the intratumoral hypoxic gradient in which the cancer stem cells niche is located in the hypoxic necrotic core of the tumour. The purpose of this study was to investigate the relationship between O(6)-methylguanine-DNA methyltransferase (MGMT) promoter methylation status and MGMT expression in GBM samples collected according to the three-layer concentric model. Multiple tissue samples were obtained, by means of image-guided surgery, from the three concentric layers of newly diagnosed GBM. Two samples from each layer were collected from 12 patients (total 72 samples). Immunohistochemical analysis was performed on formalin-fixed paraffin-embedded tissue samples. The methylation status of the MGMT promoter was determined by methylation-specific polymerase-chain-reaction analysis. In all tumours, MGMT protein expression decreased progressively from the inner to the outer layer, and methylation of the MGMT promoter was unrelated to tumour layer. In particular, the MGMT promoter was unmethylated in all layers in 41.7% of tumours, methylated in all layers in 25%, and variably methylated in the three layers in 33.3%. We recorded concordance between MGMT expression and MGMT promoter methylation status within the GBM in only 58.8% of the samples collected. Our data suggest that both MGMT expression and promoter methylation data may be variable throughout GBM and that they may, consequently, depend on the site of surgical sample collection, even in the same patient. However, whereas MGMT expression is pre-operatively predictable when sampling is performed according to the three-layer concentric model, MGMT promoter methylation is not. These results must be considered when sample collection is performed for assessment of MGMT data.

Diagnostic Value of Plasma and Urinary 2-Hydroxyglutarate to Identify Patients With Isocitrate Dehydrogenase-Mutated Glioma

BACKGROUND Mutant isocitrate dehydrogenase (IDH) 1/2 enzymes can convert α-ketoglutarate into 2-hydroxyglutarate (2HG). The aim of the present study was to explore whether 2HG in plasma and urine could predict the presence of IDH1/2 mutations in patients with glioma. MATERIALS AND METHODS All patients had histological confirmation of glioma and a recent brain magnetic resonance imaging scan showing the neoplastic lesion. Plasma and urine samples were taken from all patients, and the 2HG concentrations were determined using liquid chromatography tandem mass spectrometry. RESULTS A total of 84 patients were enrolled: 38 with R132H-IDH1 mutated and 46 with wild type. Among the 38 patients with mutant IDH1, 21 had high-grade glioma and 17 had low-grade glioma. Among the 46 patients with IDH1 wild-type glioma, 35 and 11 had high- and low-grade glioma, respectively. In all patients, we analyzed the mean 2HG concentration in the plasma, urine, and plasma/urine ratio (Ratio_2HG). We found a significant difference in the Ratio_2HG between patients with and without an IDH1 mutation (22.2 ± 8.7 vs. 15.6 ± 6.8; p < .0001). The optimal cutoff value for Ratio_2HG to identify IDH1 mutation was 19 (sensitivity, 63%; specificity, 76%; accuracy, 70%). In the patients with high-grade glioma only, the optimal cutoff value was 20 (sensitivity, 76%; specificity, 89%; accuracy, 84%; positive predictive value, 80%; negative predictive value, 86%). In 7 of 7 patients with high-grade glioma, we found a correlation between the Ratio_2HG value and the response to treatment. CONCLUSION Ratio_2HG might be a predictor of the presence of IDH1 mutation. The measurement of 2HG could be useful for disease monitoring and also to assess the treatment effects in these patients.

Microsurgical endoscopy-assisted presigmoid retrolabyrinthine approach as a minimally invasive surgical option for the treatment of medium to large vestibular schwannoma

Background Treatment of vestibular schwannomas presents many controversial aspects, from the indication to the selection of the best treatment option. In the era of stereotactic radiotherapy, microsurgery has to be competitive in terms of providing the best chances of functional preservation and complete tumor removal. The two most commonly used surgical approaches are the retrosigmoid suboccipital and the presigmoid translabyrinthine. We describe the endoscopy-assisted presigmoid retrolabyrinthine approach (EAPRA) aiming at combining the advantages of the retrosigmoid and translabyrinthine techniques.

Multifocal presentation of medulloblastoma in adulthood

Medulloblastoma in adulthood is uncommon but not rare; annual incidence is 2–20/1,000,000. Some peculiarities characterize medulloblastoma in adult patients compared with the child type: lateral cerebellar location, heterogeneous signal intensity on magnetic resonance imaging, desmoplastic histological variant, and more favourable prognosis. Preoperative diagnosis is crucial for correct management of these patients. However, because of the low incidence of medulloblastoma in the adult population, preoperative diagnosis remains challenging and prognostic factors and best treatment options are still controversial. In this setting, some unusual findings, for example multifocal presentation and extra-axial location, can confound diagnosis and make treatment difficult. We present a short case-illustrated review on these remarkable issues.

8-Hydroxynaphthalene-1,4-dione derivative as novel compound for glioma treatment

Malignant gliomas continue to demand the search for improved chemotherapeutic solutions. In this work the results of a preliminary in vitro screening performed on a small library of compounds are disclosed. As a result 2-(2,4-dihydroxyphenyl)-8-hydroxy-1,4-naphthoquinone emerged as a promising therapeutic lead.

Hypophyseal Triplication: Case Report and Embryologic Considerations

SUMMARY: Hypophyseal triplication is malformation that has not been described previously. We present a child with midline abnormalities who underwent epignathus excision at birth. Brain MR imaging revealed 2 paired lateral pituitary glands and an oval midline gland, each with an independent stalk, connected to a thickened third ventricle floor. Because malformations represent a failure in embryogenesis, this case may provide interesting clues on the normal development of the hypophysis.

Retrolabyrinthine Meatotomy as Part of Retrosigmoid Approach to Expose the Whole Internal Auditory Canal: Rationale, Technique, and Outcome in Hearing Preservation Surgery for Vestibular Schwannoma

BACKGROUND Vestibular schwannoma extending to the fundus of the internal auditory canal is currently considered an unfavorable condition for hearing preservation surgery via a retrosigmoid approach because the lateral end of the canal is hard to view directly during microsurgery. OBJECTIVE To present an improved retrolabyrinthine meatotomy (RLM) technique that enables the full length of the cochlear and facial nerves to be inspected up to their orifices on the fundus. Long-term results are briefly reported. METHODS A consecutive series of 100 cases with various degrees of fundus involvement underwent surgery via a retrosigmoid approach and RLM. The follow-up ranged from 4 to 14 yr. Outcomes on hearing and facial nerve function were recorded, and preoperative MRI findings of the tumor on the fundus were correlated with the surgical findings and the long-term radicality of the tumor resection. RESULTS Residual tumor on the fundus was identified in 3 cases, all belonging to the group with tumors adhering to the fundus. The functional results were in line with the best reported outcomes of this surgery. CONCLUSION RLM via a retrosigmoid approach seemed adequate for the purposes of hearing preservation surgery and enabled the full course of the facial and cochlear nerves through the internal auditory canal to be exposed to direct view. Tumors adhering to the vestibular quadrant of the fundus were more difficult to remove, and there were a few cases of local residual tumor.

Addressing the selective role of distinct prefrontal areas in response suppression: A study with brain tumor patients

&NA; The diverging evidence for functional localization of response inhibition within the prefrontal cortex might be justified by the still unclear involvement of other intrinsically related cognitive processes like response selection and sustained attention. In this study, the main aim was to understand whether inhibitory impairments, previously found in patients with both left and right frontal lesions, could be better accounted for by assessing these potentially related cognitive processes. We tested 37 brain tumor patients with left prefrontal, right prefrontal and non‐prefrontal lesions and a healthy control group on Go/No‐Go and Foreperiod tasks. In both types of tasks inhibitory impairments are likely to cause false alarms, although additionally the former task requires response selection and the latter target detection abilities. Irrespective of the task context, patients with right prefrontal damage showed frequent Go and target omissions, probably due to sustained attention lapses. Left prefrontal patients, on the other hand, showed both Go and target omissions and high false alarm rates to No‐Go and warning stimuli, suggesting a decisional rather than an inhibitory impairment. An exploratory whole‐brain voxel‐based lesion‐symptom mapping analysis confirmed the association of left ventrolateral and dorsolateral prefrontal lesions with target discrimination failure, and right ventrolateral and medial prefrontal lesions with target detection failure. Results from this study show how left and right prefrontal areas, which previous research has linked to response inhibition, underlie broader cognitive control processes, particularly involved in response selection and target detection. Based on these findings, we suggest that successful inhibitory control relies on more than one functionally distinct process which, if assessed appropriately, might help us to better understand inhibitory impairments across different pathologies. HighlightsInhibitory and other co‐occurring processes were investigated in brain tumor patients.Attentional lapses in terms of target misses were observed in right frontal patients.Decisional impairment concerning response selection was found in left frontal patients.These results were confirmed by a voxel‐based lesion‐symptom mapping analysis.Broader cognitive control deficits can account for errors in inhibitory task contexts.

What’s growing on? The growing teratoma syndrome

BackgroundThe growing teratoma syndrome (GTS) consists of a mature teratoma paradoxically enlarging during or after chemotherapy for malignant nongerminomatous germ cell tumors.Methods and resultsWe report two cases of GTS occurring in association with NSGCT of the pineal gland. Although an unusual event, clinicians and radiologists should be aware of its natural history.ConclusionsWhen normalized tumor markers after chemotherapy are associated with imaging features of a growing mass, the hypothesis of GTS must be taken in consideration. When early diagnosed, GTS can be managed surgically with good results.