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Introduction. Today we observe an increase in brain tumor incidence around the world, and glioma is no exception. Gliomas are still among the most frequently diagnosed primary central nervous system tumors despite a large number of glioma management studies. Their control still remains a challenge. It is necessary to create specialized cryogenic storage with a systematized databank that could provide a basis for more profound studies of their pathogenesis and invasion patterns. There are about 20 biorepository facilities in Russia; however, they do not focus on a particular tumor type. The aim of the study was to develop the spe-cific biobank of glial tumors integrated with a dedicated electronic system containing all associated clinical data necessary for the research purposes. Materials and methods. The required amount of material sampling was carried out during the surgical resec-tion in patients with a preliminary diagnosis of “malignant glioma”, followed by processing, cryopreserva-tion, and passportization. Results. Between August 1, 2018, and April 30, 2020, a total of 1,452 aliquots from 358 subjects were ac-cumulated in the biobank. Each frozen sample corresponded to a paraffin block and provided with the whole set of associated demographic, clinical, histological, and follow-up data. All these records were stored in the electronic information system. During this study, the design of the glioma passport was developed. Conclusion. The development of an appropriate facility is necessary for efficient further experimental re-search. It offers an opportunity for future implementation of personalized treatment methods after a full clinical trial cycle. Keywords: neurooncology, glioma, glioblastoma, biobank, biorepository

ObjectivesTo perform an adequate orbito-zygomatic craniotomy, it is very important that the bone cut which passes through the body of the zygoma reaches the inferior orbital fissure (IOF). To reach the IOF, two surface landmarks on the body of the zygoma are described: a point located directly superior to the malar eminence and the zygomaticofacial foramen. The article explores the reliability of these landmarks and three other alternative points to reach the IOF.Method Eighty-three adult skulls were used in this study. The IOF dimensions and the relationship with the malar eminence, the point superior to the malar eminence, the zygomaticofacial foramen and 3 alternative points (E, C, F) were analyzed.Results. The malar eminence was unacceptable for use as a guide to the IOF. The point superior to the malar eminence was also unacceptable as a guide as only 9.4% and 10.9% were in the projection of the IOF on the right and left, respectively. 59.7% of the total zygomaticofacial foramina fell in the IOF projection. The point F fell in the projection of the IOF in 98.8% and 100.0% on the right and left, respectively. Conclusion. The use of the malar eminence as a guide to reach the IOF is unreliable in one third of cases as it is not easily identified intraoperatively in these cases. The zygomaticofacial foramen cannot be considered a reliable surgical landmark to reach the IOF. The authors recommend using the point “F” which is reliable in 98.8-100% of cases.

To perform an adequate orbitozygomatic craniotomy, it is very important that the bone cut which passes through the body of the zygoma reaches the inferior orbital fissure (IOF). To reach the IOF, two surface landmarks on the body of the zygoma are described: a point located directly superior to the malar eminence and the zygomaticofacial foramen. The article explores the reliability of these landmarks and three other alternative points to reach the IOF. Eighty-three adult skulls were used in this study. The IOF dimensions and the relationship with the malar eminence, the point superior to the malar eminence, the zygomaticofacial foramen, and 3 alternative points (E, C, F) were analyzed. The malar eminence was unacceptable for use as a guide to the IOF. The point superior to the malar eminence was also unacceptable as a guide as only 9.4% and 10.9% were in the projection of the IOF on the right and left, respectively. 59.7% of the total zygomaticofacial foramina fell in the IOF projection. The point F fell in the projection of the IOF in 98.8% and 100.0% on the right and left, respectively. The use of the malar eminence as a guide to reach the IOF is unreliable in one third of cases as it is not easily identified intraoperatively in these cases. The zygomaticofacial foramen cannot be considered a reliable surgical landmark to reach the IOF. The authors recommend using a novel landmark which may be identified as a midpoint between intersections of the anterior and posterior margins of the zygomatic frontal process on a line extending from the inferior margin of the zygomatic arc. This point is reliable in 98.8-100% of cases.

Glioblastoma (GBM) is the most aggressive nervous system cancer. Understanding its molecular pathogenesis is crucial to improving diagnosis and treatment. Integrated analysis of genomic, proteomic, post-translational modification and metabolomic data on 99 treatment-naive GBMs provides insights to GBM biology. We identify key phosphorylation events (e.g., phosphorylated PTPN11 and PLCG1) as potential switches mediating oncogenic pathway activation, as well as potential targets for EGFR-, TP53-, and RB1-altered tumors. Immune subtypes with distinct immune cell types are discovered using bulk omics methodologies, validated by snRNA-seq, and correlated with specific expression and histone acetylation patterns. Histone H2B acetylation in classical-like and immune-low GBM is driven largely by BRDs, CREBBP, and EP300. Integrated metabolomic and proteomic data identify specific lipid distributions across subtypes and distinct global metabolic changes in IDH-mutated tumors. This work highlights biological relationships that could contribute to stratification of GBM patients for more effective treatment. Wang et al. perform integrated proteogenomic analysis of adult glioblastoma (GBM), including metabolomics, lipidomics, and single nuclei RNA-Seq, revealing insights into the immune landscape of GBM, cell-specific nature of EMT signatures, histone acetylation in classical GBM, and the existence of signaling hubs which could provide therapeutic vulnerabilities.

Background The aim of the project was to show the peculiarities of manipulations in two-dimensional (2D) visualization and to enlighten young neurosurgical residents for further independent training of their manual skills in the anatomic lab. The course followed a step-by-step training program starting with artificial models in a static 2D exoscopic view field with subsequent transition to cadaveric animal models and the use of dynamic four-hand techniques and endoscopy. Materials and methods Since 2015, two 2-day workshops and four 1-day workshops have been organized. All courses consisted of short theoretical and prevailing hands-on practical part and were designed mainly for manual skills training. For optimal practical training, each pair of trainees were engaged with a separate working place equipped with a video system, exoscope, drill, suction, and a set of microsurgical and endoscopic instruments. A total of 48 trainees, including residents of the Nikolay Nilovich (NN) Burdenko National Medical Research Center of Neurosurgery (NMRCN), the Russian Medical Academy of Continuous Postgraduate Education, and other institutions from different regions of Russia, completed the program. Analysis of evaluation sheets revealed that over 90% of trainees were under the age of 30. Results The key idea – accommodation to endoscopy through a series of microsurgical exercises in 2D visualization – has been successfully actualized and met with interest. After analyzing the questionnaires, we found that an overall satisfaction rate was high. The vast majority of trainees intended to gain further experience and apply new techniques in their clinical neurosurgical and microsurgical practice. The number of practiced techniques and the quality of the provided equipment were considered by the participants as good or very good. The highly individualized training course with a participant/tutor ratio of 4:1 and the use of tissue models (no sacrifice of living animals) was well appreciated. Conclusion The demand for a workshop indicates a lack of such training activities for young professionals, such as the one we presented herein. Evaluation of the courses by the trainees showed that the contents of workshops corresponded to their tasks and expectations, regardless of their previous experience. The workshop was not only the 'stepping stone' from which the path of practical self-development should begin but also initiated the development of a whole series of specially focused training workshops on microsurgery and endoscopy for neurosurgeons.

Ligation of the sphenopalatine and posterior nasal arteries is indicated for posterior epistaxis as initial treatment or when conservative measures fail. In some patients, a transnasal approach or its alternative transantral approach are not possible due to tumor filling the nasal corridor, pterygopalatine fossa, or maxillary sinus. Aim of this study was to evaluate feasibility of endoscopically assisted transoral approach for the ligation of the maxillary artery (MA). Six fresh cadaver specimens (12 sides), previously prepared with intravascular injections of colored latex, were dissected. A combined transnasal and transoral approach exposed the MA from the deep belly of the temporalis muscle laterally to its terminal branches medially. Anatomical relationships of the MA with the deep belly of the temporalis muscle and the lower head of the lateral pterygoid muscle, and feasibility of access to the MA via a transoral approach were assessed. In all specimens, the MA was found at the point where horizontal fibers of the lower head of the lateral pterygoid muscle cross the vertical fibers of the deep belly of the temporalis muscle. In 5 specimens, the artery ran anteriorly and laterally to lower head of the lateral pterygoid muscle, and in 1 specimen, it ran posteriorly and medially to this muscle, diving between its fibers. The modified endoscopically assisted transoral approach is feasible to ligate the MA. It can be used for proximal vascular control in cases when transnasal and transantral approaches are not viable.

Nasal chondromesenchymal hamartoma (NCMH) is a rare benign tumor of the sinonasal tract in children with possible orbit and skull base involvement. We present the 57th published observation of this kind of tumor. A 25-month-old female patient presented with recurrent mass lesion of the sinonasal tract. According to her history, she had feeding difficulties and nasal obstruction since birth. She underwent partial resection at eight months of age via transfacial approach in the local hospital. Due to progression of tumor remnants, a second surgery was performed using an endoscopic endonasal approach resulting in subtotal resection. At 12 months of follow-up, a good postoperative result was observed with no signs of tumor progression despite incomplete resection. Histological and immunohistochemical examination of the biopsy specimens is presented. Comparison of specimens obtained from each of the two surgeries showed a difference in histological patterns. Endoscopic endonasal approach is the mainstay of surgical management. In case of incomplete resection, careful follow-up MRI studies should be recommended.

Novel equipment for surgery navigation thru photodynamic diagnosis is presented with laser fluorescence excitation and dual channel video registration. This equipment could be incorporated in a standard surgery tool like aspirator canule. It is based on fiberoptic endoscope with special channels for laser illumination in red and blue spectral ranges and video head based on two spectrally-resolved cameras.

International audience; A 5-ALA-induced fluorescence-based imaging device for guidance during surgery of malignant and non-malignant preliminary photosensitized tumors is presented. The setup fits existing clinical optical rigid and flexible endoscopes and operation microscopes. It consists of three light sources including white light, red light fluorescence excitation and blue light fluorescence excitation sources. The light from any combination of the latter sources is delivered to tissue using specially designed fiber optic light guide. Two cameras are used to acquire fluorescence and back reflected white light images: a gray-level camera for fluorescence in the far red range and a color camera for white light images. A dichroicmirror is implemented to spectrally split the light coming from tissue. Images from both cameras are processed into a computer with specially developed software where it can be displayed in different modes including overlaying or been used for image mosaicing which allows for increasing the intrinsic reduced field of view of endoscopes by providing highly resolved extended cartography. Experiments were carried out on phantoms and on patients in clinical conditions during surgery of brain and other tissues. Blue light excitation was more sensitive for thin tumors but red light excitation was more beneficial for solid tumors and for navigation in presence of slight bleeding.

Introduction: Preoperative stereotactic radiosurgery (pre-SRS) is a recent advancement in the strategy for brain metastasis (BM) management, and available data demonstrate the advantages of pre-SRS before postoperative radiation treatment, including lower rates of local toxicity, leptomeningeal progression, and a high percentage of local control. The authors presented the results of pre-SRS in patients with BM. Materials and methods: Nineteen patients with BM (11 female and eight male) have been treated at N.N. Burdenko Medical Research Center for Neurosurgery (Moscow, Russia) and Gamma-Knife Center (Moscow, Russia) using pre-SRS. A total of 22 symptomatic metastatic lesions were preoperatively irradiated in the series. Eight patients had multiple BM (number of metastases ranged between two and seven). The median target volume for combined treatment was 14.131 cc (volumes varied between 2.995 and 57.098 cc; mean - 19.986 cc). The median of the mean target dose was 18 Gy, ranging between 12.58 and 24.36 Gy. Results: All patients tolerated pre-SRS well, without any neurological deterioration, and surgical treatment was performed as scheduled. The median follow-up period was 6.3 months (ranging between five weeks and 22.9 months). In 17 out of 19 patients, follow-up magnetic resonance (MR) images obtained two or three months after the combined treatment demonstrated the postoperative cavity without any signs of postradiation alterations in the perifocal tissues. In two observations, peritumoral edema was present. Local recurrences were found in two cases, 5.5 and 17.4 months after treatment. Radionecrosis was present in one observation after 4.6 months of follow-up. Two patients died of disease progression and are presented as illustrative cases. Conclusion: The combined treatment of secondary brain tumors has proved to be the best treatment option. Preoperative stereotactic radiosurgery may decrease radiation-induced toxicity and rates of local tumor progression. The potential hazards of pre-SRS associated with the postoperative healing of irradiated soft tissues of the head were not confirmed in our study. The decision of pre-SRS should be made by the tumor board, including specialists in neurosurgery, neuro-oncology, and radiation oncology, if the diagnosis of BM is based on oncological history and visualization data.

e14670 Background: A major determinant of cancer resistance and recurrence is the presence of quiescent cancer cells. It has long been known that quiescent cancers are resistant to a wide variety of anti-cancer therapeutics relative to actively proliferating cells. However, the presence and relative size of the quiescent compartment is not revealed by standard H&E staining and morphological tumor analysis and, therefore, the data demonstrating its importance and prevalence by tumor type are lacking. DYRK1B kinase (serine/threonine-protein kinase dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 1B) is associated with growth and survival of many types of cancer cells and was shown to play a key role in maintaining the cancer cells in reversible quiescent state by stabilizing the CDK inhibitor p27 and by inducing the breakdown of cyclin D isoforms. Methods: We conducted an immunohistochemical study of 80 human glioblastoma (GBM) tumors (primary / treatment-naive, Grade IV) and 10 cases of normal postmortem brain tissues for expression of DYRK1B, and quiescence and proliferation markers p27 and Ki-67, respectively. For subsection of these tissues, high levels of DYRK1B and p27 expression were observed. Results: In this study, we investigated the functional and therapeutic relevance of DYRK1B expression in glioblastomas, the most common brain cancer in adults. It is an aggressive, highly resistant to treatment tumor type with median survival time of less than 16 months following surgery and treatment. Conclusions: There was a statistically significant correlation between immunostaining of DYRK1B and p27, indicating the presence of dormant cancer cells mixed with the proliferating cancer cells within the patients' tumors. We suggest that DYRK1B inhibitors in combination with chemotherapeutics agents have a potential to improve patient treatment outcome and prolong survival.

Objectives To evaluate the efficacy and safety of using a buccal fat pad for endoscopic skull base defect reconstruction. Design Descriptive anatomical study with an illustrative case presentation. Setting Anatomical study was performed on 12 fresh human cadaver specimens with injected arteries (24 sides). Internal carotid artery was exposed in the coronal plane via the endoscopic transpterygoid approach. The pedicled buccal fat pad was used for reconstruction. Participants: 12 human cadaver head specimens; one patient operated using the proposed technique. Main outcome measures: Proximity of the buccal fat pad flap to the defect, compliance of the flap, comfort and safety of harvesting procedure, and compatibility with the Hadad–Bassagasteguy nasoseptal flap. Results: Harvesting procedure was performed using anterior transmaxillary corridor. The pedicled buccal fat pad flap can be used to pack the sphenoid sinus or cover the internal carotid artery from cavernous to upper parapharyngeal segment. Conclusion The buccal fat pad can be safely harvested through the same approach without external incisions and is compliant enough to conform to the skull base defect. The proposed pedicled flap can replace free abdominal fat in central skull base reconstruction. The volume of the buccal fat pad allows obliteration of the sphenoid sinus or upper parapharyngeal space.

BACKGROUND: Problem of closure of skull base defects after removal of craniobasal lesions, especially, craniofacial, is one of the most challenging in neurosurgery. Persistent skull base defect produces extremely high risk of cerebrospinal fluid leaks and consecutive infectious complications. Local pedicled grafts are the preferred material for plasty. In this study, the authors present original technique of using a pedicled buccal fat pad (BFP) graft. Anatomy and functions of BFP are discussed in details as well as surgical technique illustrated by 2 case reports. METHODS: From 2004 to 2010, 188 patients with anterior and middle skull base mass lesions were operated on in Burdenko Neurosurgical Institute (Moscow, Russia) using BFP as plastic material for closure of different defects (male-female ratio=61:127; mean age was 47 years [range, 10-74 years]). RESULTS: In 93.6% of cases, pedicled BFP flap was applied; in 6.4%, free flap was used. Follow-up period ranged between 1 and 7 years. Only 1 case of postoperative cerebrospinal fluid leak was observed; flap rejection was not registered in the series. CONCLUSIONS: High effectiveness and minimal invasiveness are principal advantages of the described technique, which is applied in neurosurgery for the first time. Other benefits include proximity of donor site and defect, simplicity of surgical technique, minimal postoperative discomfort, and very low risk of benign complications.

Background 5-Aminolevulinic acid (5-ALA) fluorescence-guided microsurgical resections have proved to be superior to conventional microsurgery of malignant brain tumors. New neuroendoscopes have recently become available which allow endoscopically assisted 5-ALA fluorescence-guided resections to be carried out during conventional microsurgery. A prospective randomized controlled phase I/II study was started in Burdenko Neurosurgical Institute at the end of 2007 in order to assess the feasibility and safety of this technique. The aim of this publication is to describe our first experience of applying this method. Materials and methods The primary tumor diagnosis included malignant glioma (WHO-grade IV), metastases (MTS) and malignant skull base tumors. A total of 17 patients were given 5-ALA prior to microsurgery of the brain tumor. Microsurgical resections were assisted by 5-ALA fluorescence-guided endoscopy using Karl Storz endoscopic equipment for the determination of tumor remnants in the resection cavity. Results The additional use of the endoscope was accepted by all surgeons as a feasible and straightforward procedure. In most cases surgeons acknowledged benefit from the possibility of controlling the “behind the border” regions of the resection cavity, i.e. thorough inspection of the entire surface of the resection cavity without any traction to brain tissue using the angled endoscope. Bright fluorescence was observed not only in gliomas grade IV, but also in three of four metastases, amongst them a single melanoma, a single case of pilocytic astrocytoma, and a single case of chordoma. Conclusions 5-ALA fluorescence-guided endoscopic assistance seems to be a feasible and beneficial technique. The use of 5-ALA fluorescence guidance may be extended to a number of brain tumors other than glioma grade IV. The technique is useful for distinguishing between normal brain and tumor tissue. No procedural or drug-related complications were observed.

Pineoblastoma is a rare malignant tumor of the central nervous system (CNS), which arises from the parenchyma of the pineal gland. It is characterized by aggressive clinical behavior and frequent metastases along the craniospinal axis. Extraneural metastases may occur due to surgical seeding of tumor cells beyond the dura and/or hematogenous spread, ventriculoperitoneal shunting, or through Batson's plexus. To our knowledge, only six documented cases of intraosseous metastases of pineoblastoma are described in the literature. A 23-year-old female patient presented with clinical and radiological symptoms of a pineal tumor causing secondary hydrocephalus. After initial surgical treatment, chemotherapy, and local radiotherapy with craniospinal irradiation, she developed multiple metastases affecting the anterior skull base, intracranial meninges, frontal bone, and finally, the entire vertebral column. The patient received surgical treatment for the anterior skull base metastasis, repeated irradiation of the neuraxis, radiosurgical and radiotherapeutic procedures, and chemotherapy. The patient survived 57 months after the primary disease manifestation and died of multiple metastases. This presented case is the first known description of metastasis of pineoblastoma in the anterior cranial base. Multiple intracranial metastases were suppressed using CyberKnife radiation treatment and chemotherapy until massive involvement of spinal column occurred. Interestingly, no signs of brain radiation necrosis after repeated radiation treatments were observed, and the patient developed only moderate neurocognitive decline.

Craniofacial chondroid tumors (CFCTs) constitute less than 1% of all intracranial mass lesions. No protocol for evaluation and management of CFCTs is developed at the moment.We analyzed 51 patients with CFCTs operated on in Burdenko Neurosurgical Institute from 1980 until 2012, which included chondroma (15), chondroblastoma (3), chondromyxoid fibroma (11), and chondrosarcoma (22). Age varied from 2 to 76 years (mean, 40 y); the series included 23 women and 28 men. All tumors were divided into 4 groups: midline unilateral (8),midline bilateral (21), anterolateral (19), and lateral (3). This division was based on differences in surgical approaches (P = 0.009).All patients underwent surgical treatment. Complete removal was achieved in 20; subtotal, in 21; and partial, in 10. Two patients died, and early complications were observed in 10 cases. Early outcomes correlated with the benign nature of the tumors (P = 0.002). Follow-up data were available in 22 patients. Fifteen of 51 patients were reoperated on because of recurrence (a total of 43 reoperations were performed). The mean recurrence-free period was 45 months. In 3 patients, the tumor metastasized, and malignant transformation was observed in 3 cases. Sixteen patients received postoperative radiation therapy. Delayed sequelae occurred in 5 observations, and 5 patients died during long-term follow-up. Three-year survival in benign and malignant tumors was 87.5% and 55.6%, respectively, and 5-year survival was 83.3% and 40.0%, respectively.Surgical resection is the mainstay in treatment of both benign and malignant craniofacial tumors, and adjuvant radiation therapy is mandatory in malignant lesions; however, it should be avoided in benign lesions.