Publications by authors named "Viscardo Paolo Fabbri"

11 Publications

  • Page 1 of 1

Infra-Temporal and Pterygo-Palatine Fossae Tumors: A Frontier in Endoscopic Endonasal Surgery-Description of the Surgical Anatomy of the Approach and Report of Illustrative Cases.

Int J Environ Res Public Health 2022 05 25;19(11). Epub 2022 May 25.

Programma Neurochirurgia Ipofisi-Pituitary Unit, IRCCS Istituto delle Scienze Neurologiche di Bologna, 40139 Bologna, Italy.

Infratemporal and pterygopalatine fossae (ITF and PPF) represent two complex paramedian skull base areas, which can be defined as jewelry boxes, containing a large number of neurovascular and osteomuscular structures of primary importance. They are in close communication with many craniofacial areas, such as nasal/paranasal sinuses, orbit, middle cranial fossa, and oral cavities. Therefore, they can be involved by tumoral, infective or inflammatory lesions spreading from these spaces. Moreover, they can be the primary site of the development of some primitive tumors. For the deep-seated location of ITF and PPF lesions and their close relationship with the surrounding functional neuro-vascular structures, their surgery represents a challenge. In the last decades, the introduction of the endoscope in skull base surgery has favored the development of an innovative anterior endonasal approach for ITF and PPF tumors: the transmaxillary-pterygoid, which gives a direct and straightforward route for these areas. It has demonstrated that it is effective and safe for the treatment of a large number of benign and malignant neoplasms, located in these fossae, avoiding extensive bone drilling, soft tissue demolition, possibly unaesthetic scars, and reducing the risk of neurological deficits. However, some limits, especially for vascular tumors or lesions with lateral extension, are still present. Based on the experience of our multidisciplinary team, we present our operative technique, surgical indications, and pre- and post-operative management protocol for patients with ITF and PPF tumors.
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http://dx.doi.org/10.3390/ijerph19116413DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9180479PMC
May 2022

A 13-Gene DNA Methylation Analysis Using Oral Brushing Specimens as an Indicator of Oral Cancer Risk: A Descriptive Case Report.

Diagnostics (Basel) 2022 Jan 23;12(2). Epub 2022 Jan 23.

Functional and Molecular Neuroimaging Unit, Bellaria Hospital, Department of Biomedical and Neuromotor Sciences, University of Bologna, 40139 Bologna, Italy.

Analysis of genetic or epigenetic markers from saliva or brushing specimens has been proposed as a diagnostic aid to identify patients at risk of developing oral cancer. However, no reliable non-invasive molecular method for this purpose is commercially available. In the present report, we describe the potential application of a procedure based on a 13-gene DNA methylation analysis using oral brushing samples from a patient affected by oral leukoplakia who developed two metachronous oral carcinomas during the follow-up period. A positive or a negative score was calculated for each brushing sample based on a predefined cut-off value. In this patient, a positive score was detected in the oral leukoplakia diagnosed more than 2 years before the development of oral squamous cell carcinoma and subsequently in clinically healthy mucosa 8 months before the appearance of a secondary tumor. This suggests a potential role of our procedure as an indicator of oral cancer risk.
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http://dx.doi.org/10.3390/diagnostics12020284DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8870863PMC
January 2022

Validation of a Cleanroom Compliant Sonication-Based Decellularization Technique: A New Concept in Nerve Allograft Production.

Int J Mol Sci 2022 Jan 28;23(3). Epub 2022 Jan 28.

Oral and Maxillofacial Surgery Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy.

Defects of the peripheral nervous system are extremely frequent in trauma and surgeries and have high socioeconomic costs. If the direct suture of a lesion is not possible, i.e., nerve gap > 2 cm, it is necessary to use grafts. While the gold standard is the autograft, it has disadvantages related to its harvesting, with an inevitable functional deficit and further morbidity. An alternative to autografting is represented by the acellular nerve allograft (ANA), which avoids disadvantages of autograft harvesting and fresh allograft rejection. In this research, the authors intend to transfer to human nerves a novel technique, previously implemented in animal models, to decellularize nerves. The new method is based on soaking the nerve tissues in decellularizing solutions while associating ultrasounds and freeze-thaw cycles. It is performed without interrupting the sterility chain, so that the new graft may not require post-production γ-ray irradiation, which is suspected to affect the structural and functional quality of tissues. The new method is rapid, safe, and inexpensive if compared with available commercial ANAs. Histology and immunohistochemistry have been adopted to evaluate the new decellularized nerves. The study shows that the new method can be applied to human nerve samples, obtaining similar, and, sometimes better, results compared with the chosen control method, the Hudson technique.
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http://dx.doi.org/10.3390/ijms23031530DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8836166PMC
January 2022

Diagnostic challenges of an incidental finding: case report of definitely-congenital glioblastoma multiforme in a very preterm infant.

Ital J Pediatr 2021 Dec 14;47(1):234. Epub 2021 Dec 14.

Neonatal Intensive Care Unit, IRCCS Policlinico di S. Orsola, S. Orsola-Malpighi Hospital, Via Massarenti 11, 40138, Bologna, Italy.

Background: Congenital brain tumors are extremely rare in the neonatal population, and often associated with a poor prognosis. The diagnostic suspicion is often aroused at antenatal scans or postnatally, if clinical signs and symptoms of increased intracranial pressure become evident. We present a case of definitely congenital glioblastoma multiforme incidentally diagnosed in a preterm infant, aiming to raise clinical awareness on this condition and to highlight the challenges of the related diagnostic work-up.

Case Presentation: This female infant was born at 31 weeks' gestation after an uneventful pregnancy. No abnormalities were detected at antenatal ultrasound scans and genetic tests. Head circumference at birth was on the 25th centile. A routine brain ultrasound scan performed on day 1 revealed a large, inhomogeneous lesion in the right cerebral hemisphere, with contralateral midline shift, which was confirmed by brain magnetic resonance imaging (MRI). Eye fundus and routine blood exams, including platelets count, coagulation screening and C-reactive protein, were normal. Given the high risk of complications, surgical biopsy of the lesion was temporarily hold and a daily sonographic follow-up was undertaken. Although head circumference growth was steady on the 25th centile, progressive changes of the lesion were detected by cranial ultrasound. The repeat MRI scans showed a significant enlargement of the mass, with contralateral midline shift and signs of intralesional and intraventricular bleeding. In view of this worsening, surgical resection was performed. The histological examination of the lesion biopsy documented a GFAP+ highly cellular neoplasm, with no mutation on SMARCB1 gene. At the molecular analysis, mutations on IDH and H3F3A genes were absent, whereas MGMT promoter was unmethylated. The diagnosis was grade IV glioblastoma IDH wild-type.

Conclusions: Congenital glioblastoma multiforme is an extremely rare but highly aggressive neoplasm. Since intralesional biopsy is not often feasible in affected neonates, knowledge of the associated clinical and neuroradiological features is particularly important, as they can also add useful information on the neoplasm behavior. Specimens from open surgical resection allow to perform a definite histological analysis and an extended molecular characterization, with relevant prognostic implications.
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http://dx.doi.org/10.1186/s13052-021-01185-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8670245PMC
December 2021

Is There a Role for Surgical Resection of Multifocal Glioblastoma? A Retrospective Analysis of 100 Patients.

Neurosurgery 2021 11;89(6):1042-1051

Department of Biomedical and Neuromotor Sciences (DIBINEM), Alma Mater Studiorum University of Bologna, Italy.

Background: Glioblastoma with multiple localizations (mGBMs) can be defined as multifocal, where enhancing lesions present a connection visible on magnetic resonance imaging fluid-attenuated inversion recovery imaging, or multicentric, in the absence of a clear dissemination pathway.

Objective: To evaluate the role of the extent of resection (EOR) in the treatment of mGBMs and its correlation with overall survival (OS) and progression free survival (PFS).

Methods: One hundred patients with mGBMs were treated at our Institution between 2009 and 2019. Clinical, radiological, and follow-up data were collected. EOR of the contrast-enhancing part of lesions was classified as gross total resection (GTR, absence of tumor remnant), subtotal resection (STR, residual tumor < 30% of the initial mass), partial resection (PR, residual tumor > 30% of the initial mass), and needle or open biopsy (residual tumor > 75% of the initial mass).

Results: Approximately 15% of patients underwent GTR, 14% STR, 32% PR, and 39% biopsy. Median OS was 17 mo for GTR, 11 mo for STR, 7 mo for PR, and 5 mo for biopsy. Greater EOR was associated with a significantly longer OS than biopsy. GTR and STR were associated with a longer PFS in Kaplan-Meier survival analyses. After adjusting for age, Karnofsky performance status (KPS), number of lesions, and adjunctive therapy in multivariable Cox regression analyses, GTR, STR, and PR were still associated with OS, but only GTR remained associated with PFS.

Conclusion: Our study suggests that EOR may positively influence survival of patients with mGBM. Surgical resection can be a reasonable option when performance and access to adjuvant treatment can be preserved.
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http://dx.doi.org/10.1093/neuros/nyab345DOI Listing
November 2021

From Neurosurgical Planning to Histopathological Brain Tumor Characterization: Potentialities of Arcuate Fasciculus Along-Tract Diffusion Tensor Imaging Tractography Measures.

Front Neurol 2021 26;12:633209. Epub 2021 Feb 26.

Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy.

Tractography has been widely adopted to improve brain gliomas' surgical planning and guide their resection. This study aimed to evaluate state-of-the-art of arcuate fasciculus (AF) tractography for surgical planning and explore the role of along-tract analyses for characterizing tumor histopathology. High angular resolution diffusion imaging (HARDI) images were acquired for nine patients with tumors located in or near language areas (age: 41 ± 14 years, mean ± standard deviation; five males) and 32 healthy volunteers (age: 39 ± 16 years; 16 males). Phonemic fluency task fMRI was acquired preoperatively for patients. AF tractography was performed using constrained spherical deconvolution diffusivity modeling and probabilistic fiber tracking. Along-tract analyses were performed, dividing the AF into 15 segments along the length of the tract defined using the Laplacian operator. For each AF segment, diffusion tensor imaging (DTI) measures were compared with those obtained in healthy controls (HCs). The hemispheric laterality index (LI) was calculated from language task fMRI activations in the frontal, parietal, and temporal lobe parcellations. Tumors were grouped into low/high grade (LG/HG). Four tumors were LG gliomas (one dysembryoplastic neuroepithelial tumor and three glioma grade II) and five HG gliomas (two grade III and three grade IV). For LG tumors, gross total removal was achieved in all but one case, for HG in two patients. Tractography identified the AF trajectory in all cases. Four along-tract DTI measures potentially discriminated LG and HG tumor patients (false discovery rate < 0.1): the number of abnormal MD and RD segments, median AD, and MD measures. Both a higher number of abnormal AF segments and a higher AD and MD measures were associated with HG tumor patients. Moreover, correlations (unadjusted < 0.05) were found between the parietal lobe LI and the DTI measures, which discriminated between LG and HG tumor patients. In particular, a more rightward parietal lobe activation (LI < 0) correlated with a higher number of abnormal MD segments ( = -0.732) and RD segments ( = -0.724). AF tractography allows to detect the course of the tract, favoring the safer-as-possible tumor resection. Our preliminary study shows that along-tract DTI metrics can provide useful information for differentiating LG and HG tumors during pre-surgical tumor characterization.
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http://dx.doi.org/10.3389/fneur.2021.633209DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7952864PMC
February 2021

Proton therapy: A therapeutic opportunity for aggressive pediatric meningioma.

Pediatr Blood Cancer 2021 05 7;68(5):e28919. Epub 2021 Mar 7.

Department of Pediatrics, University of Bologna, Bologna, Italy.

Meningiomas are an extremely rare histology among pediatric brain tumors, and there is a shortage of literature on their management. Proton therapy is currently used safely and effectively for many types of both pediatric and adult cancer, and its main advantage is the sparing of healthy tissues from radiation, which could translate in the reduction of late side effects. We review the literature on radiotherapy and proton therapy for pediatric meningiomas and report clinical outcomes for two aggressive pediatric meningiomas we treated with protons. Proton therapy might be a safe and effective therapeutic option for this rare subgroup of tumors.
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http://dx.doi.org/10.1002/pbc.28919DOI Listing
May 2021

Location-dependent role of phospholipase C signaling in the brain: Physiology and pathology.

Adv Biol Regul 2021 01 28;79:100771. Epub 2020 Nov 28.

Cellular Signalling Laboratory, Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy. Electronic address:

Phosphoinositide-specific phospholipases C (PI-PLCs) are a class of enzymes involved in the phosphatidylinositol metabolism, which is implicated in the activation of several signaling pathways and which controls several cellular processes. The scientific community has long accepted the existence of a nuclear phosphoinositide (PI) metabolism, independent from the cytoplasmic one, critical in nuclear function control. Indeed, nuclear PIs are involved in many activities, such as cell cycle regulation, cell proliferation, cell differentiation, membrane transport, gene expression and cytoskeletal dynamics. There are several types of PIs and enzymes implicated in brain activities and among these enzymes, PI-PLCs contribute to a specific and complex network in the developing nervous system. Moreover, considering the abundant presence of PI-PLCβ1, PI-PLCγ1 and PI-PLCβ4 in the brain, a specific role for each PLC subtype has been suggested in the control of neuronal activity, which is important for synapse function, development and other mechanisms. The focus of this review is to describe the latest research about the involvement of PI-PLC signaling in the nervous system, both physiologically and in pathological conditions. Indeed, PI-PLC signaling imbalance seems to be also linked to several brain disorders including epilepsy, movement and behavior disorders, neurodegenerative diseases and, in addition, some PI-PLC subtypes could become potential novel signature genes for high-grade gliomas.
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http://dx.doi.org/10.1016/j.jbior.2020.100771DOI Listing
January 2021

Biomarkers of pituitary macroadenomas aggressive behaviour: a conventional MRI and DWI 3T study.

Br J Radiol 2020 Sep 6;93(1113):20200321. Epub 2020 Jul 6.

Department of Neuroradiology, Ospedale Bellaria, IRCCS Institute of Neurological Sciences of Bologna, Via Altura, 3; 40100 Bolgona, Italy.

Objective: Pituitary macroadenomas (PAs) are usually defined as benign intracranial tumors. However, they may present local aggressive course. High Ki67 labelling index (LI) values have been related to an aggressive tumor behavior. A recent clinicopathological classification of PA based on local invasiveness and proliferation indexes, divided them in groups with different prognosis. We evaluated the utility of conventional MRI (cMRI) and diffusion-weighted imaging (DWI), in predicting the Ki67- LI according the clinicopathological classification.

Methods: 17 patients (12 M and 5 F) who underwent surgical removal of a PA were studied. cMRI features, quantification of W and W signal intensity, degree of contrast uptake (enhancement ratio, ER) and apparent diffusion coefficient (ADC) values were evaluated by using a 3 T scan. Statistics included Mann-Whitney test, Spearman's test, and receiver operating characteristic analysis. A value of ≤ 0.05 was considered significant for all the tests.

Results: Negative correlations were observed between Ki-67 LI, ADCm (ρ = - 0.67, value = 0.005) and ER values (ρ = -0.62; = 0.008). ER values were significantly lower in the proliferative PA group ( = 0.028; = 0.017). ADCm showed sensitivity and specificity of 90 and 85% respectively into predict Ki67-LI value. A value of ADCm ≤0, 711 x 10-6 mm emerged as a cut-off of a value of Ki67-LI ≥ 3%.

Conclusion: Adding quantitative measures of ADC values to cMRI could be used routinely as a non-invasive marker of specific predictive biomarker of the proliferative activity of PA.

Advances In Knowledge: Routinely use of DWI on diagnostic work-up of pituitary adenomas may help in establish the likely biological aggressive lesions.
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http://dx.doi.org/10.1259/bjr.20200321DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7465851PMC
September 2020

Headache and Dural Enhancement: Two Case Studies of Different Treatable Pathologies.

World Neurosurg 2020 09 25;141:306-310. Epub 2020 Jun 25.

Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy; IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy.

Background: Hypertrophic pachymeningitis (HP) and spontaneous intracranial hypotension are different treatable diseases, which should promptly be recognized and treated to prevent neurologic sequelae. Headache and dural enhancement are the main features of both diseases, thus differentiating between these 2 conditions can be difficult.

Cases Description: We present 2 cases with headache and dural enhancement, in which the differential diagnosis was challenging at presentation because, in both cases, clear positional pain modification was not reported. Each patient was referred to us with the suspicion of a diagnosis actually affecting the other one. Based on further findings, which supported diagnosis of spontaneous intracranial hypotension in the first case and of HP in the second one, we briefly review clinical, radiologic, and laboratory features, which can help in the differential diagnosis.

Conclusions: An accurate diagnostic workup is mandatory to distinguish among HP and intracranial hypotension.
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http://dx.doi.org/10.1016/j.wneu.2020.06.126DOI Listing
September 2020

A rare case of intracranial extra-axial ependymoma.

Ultrastruct Pathol 2019 4;43(4-5):216-219. Epub 2019 Nov 4.

Department of Biomedical and Neuromotors Sciences, Anatomic Pathology at S. Orsola Hospital, University of Bologna, Bologna, Italy.

Intracranial extra-axial ependymomas (IEAEs) are extremely uncommon tumors and they could have a wide spectrum of clinical and radiological features. Here we report morphological features of an extra-axial ependymoma (radiology, histology and ultrastructural details) which mimicked the presentation of meningioma.
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http://dx.doi.org/10.1080/01913123.2019.1687632DOI Listing
April 2020
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