Is It Time for a Paradigm Shift in the Surgical Management of Trigeminal Schwannomas? Evaluating the Role of the Transorbital Approach: An Anatomo-Clinical Study and Systematic Literature Review.

BACKGROUND: Endoscopic transorbital approach emerged in recent years as an effective, minimally invasive route to access Meckel's cave area. Several case series proved its effectiveness in the surgical treatment of trigeminal schwannomas. This route provides the advantages of a minimally invasive approach associated with low morbidity rates. In this anatomo-clinical study we illustrate the usefulness of the superior eyelid transorbital approach for the surgical treatment of trigeminal schwannoma guiding the clinical applicability of the anatomical findings into real surgical practice. METHODS: Superior eyelid transorbital endoscopic approach was performed on 8 cadaveric specimens, and the surgical results were confirmed in a retrospective review of all the surgical cases of transorbital surgery performed by the senior authors providing an illustrative case. Finally, we performed a literature review of all the case series of trigeminal schwannomas operated through an endoscopic transorbital approach. RESULTS: Stepwise dissection was divided in 3 phases: skin, endo-orbital, and endocranial. The illustrative case provided demonstrate gross total resection of a cavernous sinus type trigeminal schwannomas treated through this route. Literature review revealed 68 cases of trigeminal schwannomas that were successfully treated using the transorbital approach. CONCLUSIONS: The endoscopic transorbital approach may offer a valuable alternative for the surgical treatment of trigeminal schwannomas. This technique provides a minimally invasive, direct and natural "interdural" route to the lateral wall of the cavernous sinus and Meckel's cave.

Multimodal Use of Contact Endoscopy in Neurosurgery: Case Series with Technical Note and Literature Review.

BACKGROUND: Originally adopted for the cytological screening of cervical and uterine cancer, contact endoscopy (CE) is now widely used in several fields of oncological surgery. The CE method, with magnification power up to 150x, was designed to enhance visualization and identify microscopic changes indicative of precancerous and cancerous lesions at early stages. In this pilot study, we evaluated the multimodal applications of CE during different endoscopic intracranial neurosurgical procedures. METHODS: Twenty patients with skull base lesions underwent surgery using different minimally invasive endoscopic approaches (endonasal, transorbital, and supraorbital). CE was used to distinguish the pathology from the surrounding healthy tissue by positioning the endoscope either in proximity or directly onto the target tissue. Special attention was given to the visualization of the margins of the lesion to differentiate compression/displacement from infiltration of the normal surrounding tissue. RESULTS: With its unprecedented range of magnification, CE could clearly identify the microvascular pattern and cytological architecture of a tissue not detectable by simple white light endoscopy, with no reported damage due to heat transmission or iatrogenic injuries. All the lesions diagnosed as "presumed neoplastic tissue" by CE were confirmed by histopathology. The most promising results were observed in surgeries for meningioma and pituitary adenoma, as these lesions exhibit distinctive microvascular networks. CONCLUSIONS: CE represents a new and effective technique for the in vivo identification of pathological microvascular and tissue features, allowing preservation of normal tissue during different endoscopic approaches. The use of CE could improve diagnostic accuracy and assist in intraoperative decision-making, becoming a key tool in various applications in neurosurgical field.

Targeted inhibition of the methyltransferase SETD8 synergizes with the Wee1 inhibitor adavosertib in restraining glioblastoma growth.

Despite intense research efforts, glioblastoma remains an incurable brain tumor with a dismal median survival time of 15 months. Thus, identifying new therapeutic targets is an urgent need. Here, we show that the lysine methyltransferase SETD8 is overexpressed in 50% of high-grade gliomas. The small molecule SETD8 inhibitor UNC0379, as well as siRNA-mediated inhibition of SETD8, blocked glioblastoma cell proliferation, by inducing DNA damage and activating cell cycle checkpoints. Specifically, in p53-proficient glioblastoma cells, SETD8 inhibition and DNA damage induced p21 accumulation and G1/S arrest whereas, in p53-deficient glioblastoma cells, DNA damage induced by SETD8 inhibition resulted in G2/M arrest mediated by Chk1 activation. Checkpoint abrogation, by the Wee1 kinase inhibitor adavosertib, induced glioblastoma cell lines and primary cells, DNA-damaged by UNC0379, to progress to mitosis where they died by mitotic catastrophe. Finally, UNC0379 and adavosertib synergized in restraining glioblastoma growth in a murine xenograft model, providing a strong rationale to further explore this novel pharmacological approach for adjuvant glioblastoma treatment.

Surgical management of Glioma Grade 4: technical update from the neuro-oncology section of the Italian Society of Neurosurgery (SINch®): a systematic review.

PURPOSE: The extent of resection (EOR) is an independent prognostic factor for overall survival (OS) in adult patients with Glioma Grade 4 (GG4). The aim of the neuro-oncology section of the Italian Society of Neurosurgery (SINch®) was to provide a general overview of the current trends and technical tools to reach this goal. METHODS: A systematic review was performed. The results were divided and ordered, by an expert team of surgeons, to assess the Class of Evidence (CE) and Strength of Recommendation (SR) of perioperative drugs management, imaging, surgery, intraoperative imaging, estimation of EOR, surgery at tumor progression and surgery in elderly patients. RESULTS: A total of 352 studies were identified, including 299 retrospective studies and 53 reviews/meta-analysis. The use of Dexamethasone and the avoidance of prophylaxis with anti-seizure medications reached a CE I and SR A. A preoperative imaging standard protocol was defined with CE II and SR B and usefulness of an early postoperative MRI, with CE II and SR B. The EOR was defined the strongest independent risk factor for both OS and tumor recurrence with CE II and SR B. For intraoperative imaging only the use of 5-ALA reached a CE II and SR B. The estimation of EOR was established to be fundamental in planning postoperative adjuvant treatments with CE II and SR B and the stereotactic image-guided brain biopsy to be the procedure of choice when an extensive surgical resection is not feasible (CE II and SR B). CONCLUSIONS: A growing number of evidences evidence support the role of maximal safe resection as primary OS predictor in GG4 patients. The ongoing development of intraoperative techniques for a precise real-time identification of peritumoral functional pathways enables surgeons to maximize EOR minimizing the post-operative morbidity.

MGMT and Whole-Genome DNA Methylation Impacts on Diagnosis, Prognosis and Therapy of Glioblastoma Multiforme.

Epigenetic changes in DNA methylation contribute to the development of many diseases, including cancer. In glioblastoma multiforme, the most prevalent primary brain cancer and an incurable tumor with a median survival time of 15 months, a single epigenetic modification, the methylation of the O6-Methylguanine-DNA Methyltransferase (MGMT) gene, is a valid biomarker for predicting response to therapy with alkylating agents and also, independently, prognosis. More recently, the progress from single gene to whole-genome analysis of DNA methylation has allowed a better subclassification of glioblastomas. Here, we review the clinically relevant information that can be obtained by studying MGMT gene and whole-genome DNA methylation changes in glioblastomas, also highlighting benefits, including those of liquid biopsy, and pitfalls of the different detection methods. Finally, we discuss how changes in DNA methylation, especially in glioblastomas bearing mutations in the Isocitrate Dehydrogenase (IDH) 1 and 2 genes, can be exploited as targets for tailoring therapy.

Three-Dimensional versus 2-Dimensional Endoscopic Third Ventriculostomy: Surgical Results of a Preliminary Comparative Study.

BACKGROUND: Three-dimensional (3-D) endoscopes have been widely used for a large variety of approaches in neurosurgical practice. However, in the last decade, 3-D scopes were barely used for ventricular surgery. In this study, we illustrated our preliminary experience with a 3-D endoscope for third ventriculostomy using new dedicated endoscopic equipment. METHODS: Over a 12-month period, a high-definition 3-D endoscopic third ventriculostomy (ETV) was performed in 14 patients with obstructive hydrocephalus. Patients were followed prospectively and compared retrospectively with a matched group of 16 similar patients who underwent ETV with a standard 2-dimensional (2-D) endoscope. Surgical outcome and intra- and postoperative course were retrospectively reviewed. RESULTS: 3-D ETV provided excellent surgical results, and no significant difference was shown in terms of outcome, complication, and length of hospitalization between the 2 groups. Moreover, operative time (minutes) was significantly shorter in the 3-D group than the 2-D ETV group (19.9 ± 4.8 vs. 22.9 ± 1.4, respectively; P < 0.05), and the use of the 3-D endoscope provided subjective improvements of depth perception, hand-eye coordination, and surgeon comfort. CONCLUSIONS: Our preliminary study clearly demonstrated the effectiveness of 3-D ETV and provided a significant reduction of operative time. Depth information from the 3-D scope appears to facilitate rapid and stable ETV maneuvers, representing a critical development that may become a valuable tool for neuroendoscopy.

Review of the main surgical and angiographic-oriented classifications of the course of the internal carotid artery through a novel interactive 3D model.

The course of the internal carotid artery (ICA) and its segment classifications were reviewed by means of a new and freely available 3D interactive model of the artery and the skull base, based on human neuroimages, that can be freely downloaded at the Public Repository of the University of Barcelona (http://diposit.ub.edu/dspace/handle/2445/112442) and runs under Acrobat Reader in Mac and Windows computers and Windows 10 tablets. The 3D-PDF allows zoom, rotation, selective visualization of structures, and a predefined sequence view. Illustrative images of the different classifications were obtained. Fischer (Zentralbl Neurochir 3:300-313, 1938) described five segments in the opposite direction to the blood flow. Gibo-Rothon (J Neurosurg 55:560-574, 1981) follow the blood flow, incorporated the cervical and petrous portions, and divided the subarachnoid course-supraclinoid-in ophthalmic, communicating, and choroidal segments, enhancing transcranial microscopic approaches. Bouthillier (Neurosurgery 38:425-433, 1996) divided the petrous portion describing the lacerum segment (exposed in transfacial procedures and exploration of Meckel's cave) and added the clinoid segment between the proximal and distal dural rings, of interest in cavernous sinus surgery. The Kassam's group (2014), with an endoscopic endonasal perspective, introduces the "paraclival segment," including the "lacerum segment" and part of the intracavernous ICA, and details surgical landmarks to minimize the risk of injury. Other classifications are also analyzed. This review through an interactive 3D tool provides virtual views of the ICA and becomes an innovative perspective to the segment classifications and neuroanatomy of the ICA and surrounding structures.

Pure Endoscopic Lateral Orbitotomy Approach to the Cavernous Sinus, Posterior, and Infratemporal Fossae: Anatomic Study.

Objective The aim of this anatomic study is to describe a fully endoscopic lateral orbitotomy extradural approach to the cavernous sinus, posterior, and infratemporal fossae. Material and Methods Three prefixed latex-injected head specimens (six orbital exposures) were used in the study. Before and after dissection, a computed tomography scan was performed on each cadaver head and a neuronavigation system was used to guide the approach. The extent of bone removal and the area of exposure of the targeted corridor were evaluated with the aid of OsiriX software (Pixmeo, Bernex, Switzerland). Results The lateral orbital approach offers four main endoscopic extradural routes: the anteromedial, posteromedial, posterior, and inferior. The anteromedial route allows a direct route to the optic canal by removal of the anterior clinoid process, whereas the posteromedial route allows for exposure of the lateral wall of the cavernous sinus. The posterior route is targeted to Meckel's cave and provides access to the posterior cranial fossa by exposure and drilling of the petrous apex, whereas the inferior route gives access to the pterygopalatine and infratemporal fossae by drilling the floor of the middle cranial fossa and the bone between the second and third branches of the trigeminal nerve. Conclusion The lateral orbitotomy endoscopic approach provides direct access to the cavernous sinus, posterior, and infratemporal fossae. Advantages of the approach include a favorable angle of attack, minimal brain retraction, and the possibility of dissection within the two dural layers of the cavernous sinus without entering its neurovascular compartment.

A Survey on Pituitary Surgery in Italy.

BACKGROUND: Pituitary tumors are a heterogeneous group of lesions that are usually benign. Therefore, a proper understanding of the anatomy, physiology, and pathology is mandatory to achieve favorable outcomes. Accordingly, diagnostic tests and treatment guidelines should be determined and implemented. Thus, we decided to perform a multicenter study among Italian neurosurgical centers performing pituitary surgery to provide an actual depiction from the neurosurgical standpoint. METHODS: On behalf of the SINch (Società Italiana di Neurochirurgia), a survey was undertaken with the participants to explore the activities in the field of pituitary surgery within 41 public institutions. RESULTS: Of the 41 centers, 37 participated in the present study. The total number of neurosurgical procedures performed in 2016 was 1479. Most of the procedures were performed using the transsphenoidal approach (1320 transsphenoidal [1204 endoscopic, 53 microscopic, 53 endoscope-assisted microscopic] vs. 159 transcranial). A multidisciplinary tumor board is convened regularly in 32 of 37 centers, and a research laboratory is present in 18 centers. CONCLUSIONS: Diagnosing pituitary/hypothalamus disorders and treating them is the result of teamwork, composed of several diverse experts. Regarding neurosurgery, our findings have confirmed the central role of the transsphenoidal approach, with preference toward the endoscopic technique. Better outcomes can be expected at centers with a multidisciplinary team and a full, or part of a, residency program, with a greater surgical caseload.

Fluorescein-assisted stereotactic needle biopsy of brain tumors: a single-center experience and systematic review.

Over the last years, fluorescence-based technology has begun an emergent intraoperative method for diagnostic confirmation of brain tumor tissue in stereotactic needle biopsy. However, the actual level of evidence is quite low, especially about fluorescein sodium (FL) application. This method needs to be further validated and better analyzed about its impact in clinical practice. Retrospective analysis of 11 cases with contrast-enhancing brain tumors, underwent awake stereotactic needle biopsy with intraoperative FL assistance (group 1), was verified under the operative microscope filter. This group was matched with a control group of 18 patients (group 2). In addition, a systematic literature review was performed in PubMed/Medline database according to PRISMA statement. All studies concerning FL or 5-ALA application in stereotactic biopsy as intraoperative confirmation of brain tumor tissue were included. The primary endpoint was the evaluation of diagnostic accuracy. In group 1, all fluorescent specimens were diagnostic. The number of samplings was the useful minimum and non-use of intraoperative neuropathological examination allowed to significantly reduce procedure time (42.09 vs 69.72 min of group 2). No complications occurred, and the average hospitalization time after procedure was 1.09 days (vs 2.33 of group 2). Literature analysis supports the usefulness of photodiagnosis and its high diagnostic yield especially at the core of high-grade/contrast-enhancing tumors. FL assistance during stereotactic biopsy of contrast-enhancing brain tumors may give a real-time confirmation of tumor tissue, maximizing the diagnostic yield, and reducing time of procedure, morbidity, and hospitalization.