Evgenii Belykh

Human Placenta Aneurysm Model for Training Neurosurgeons in Vascular Microsurgery

BACKGROUND: Neurosurgery, a demanding specialty, involves many microsurgical procedures that require complex skills, including open surgical treatment of intracranial aneurysms. Simulation or practice models may be useful for acquiring these skills before trainees perform surgery on human patients. OBJECTIVE: To describe a human placenta model for the creation and clipping of aneurysms. METHODS: Placental vessels from 40 human placentas that were dimensionally comparable to the sizes of appropriate cerebral vessels were isolated to create aneurysms of different shapes. The placentas were then prepared for vascular microsurgery exercises. Sylvian fissure--like dissection technique and clipping of large- and small-necked aneurysms were practiced on human placentas with and without pulsatile flow. A surgical field designed to resemble a real craniotomy was reproduced in the model. RESULTS: The human placenta has a plethora of vessels that are of the proper dimensions to allow the creation of aneurysms with dome and neck dimensions similar to those of human saccular and fusiform cerebral aneurysms. These anatomic scenarios allowed aneurysm inspection, manipulation, and clipping practice. Technical microsurgical procedures include simulation of sylvian fissure dissection, unruptured aneurysm clipping, ruptured aneurysm clipping, and wrapping; all were reproduced with high fidelity to the haptics of live human surgery. Skill-training exercises realistically reproduced aneurysm clipping. CONCLUSION: Human placenta provides an inexpensive, widely available, convenient biological tissue that can be used to create models of cerebral aneurysms of different morphologies. Neurosurgical trainees may benefit from the preoperative use of a realistic model to gain familiarity and practice with critical surgical techniques for treating aneurysms.

Prospective evaluation of the utility of intraoperative confocal laser endomicroscopy in patients with brain neoplasms using fluorescein sodium: experience with 74 cases

OBJECTIVE This study evaluated the utility, specificity, and sensitivity of intraoperative confocal laser endomicroscopy (CLE) to provide diagnostic information during resection of human brain tumors. METHODS CLE imaging was used in the resection of intracranial neoplasms in 74 consecutive patients (31 male; mean age 47.5 years; sequential 10-month study period). Intraoperative in vivo and ex vivo CLE was performed after intravenous injection of fluorescein sodium (FNa). Tissue samples from CLE imaging-matched areas were acquired for comparison with routine histological analysis (frozen and permanent sections). CLE images were classified as diagnostic or nondiagnostic. The specificities and sensitivities of CLE and frozen sections for gliomas and meningiomas were calculated using permanent histological sections as the standard. RESULTS CLE images were obtained for each patient. The mean duration of intraoperative CLE system use was 15.7 minutes (range 3-73 minutes). A total of 20,734 CLE images were correlated with 267 biopsy specimens (mean number of images/biopsy location, in vivo 84, ex vivo 70). CLE images were diagnostic for 45.98% in vivo and 52.97% ex vivo specimens. After initiation of CLE, an average of 14 in vivo images and 7 ex vivo images were acquired before identification of a first diagnostic image. CLE specificity and sensitivity were, respectively, 94% and 91% for gliomas and 93% and 97% for meningiomas. CONCLUSIONS CLE with FNa provided intraoperative histological information during brain tumor removal. Specificities and sensitivities of CLE for gliomas and meningiomas were comparable to those for frozen sections. These data suggest that CLE could allow the interactive identification of tumor areas, substantially improving intraoperative decisions during the resection of brain tumors.

Genetic Alterations in intervertebral Disc Disease

Background Intervertebral disc degeneration (IVDD) is considered a multifactorial disease that is influenced by both environmental and genetic factors. The last two decades of research strongly demonstrate that genetic factors contribute about 75% of the IVDD etiology. Recent total genome sequencing studies have shed light on the various single-nucleotide polymorphisms (SNPs) that are associated with IVDD. Aim This review presents comprehensive and updated information about the diversity of genetic factors in the inflammatory, degradative, homeostatic, and structural systems involved in the IVDD. An organized collection of information is provided regarding genetic polymorphisms that have been identified to influence the risk of developing IVDD. Understanding the proteins and signaling systems involved in IVDD can lead to improved understanding and targeting of therapeutics. Materials and methods An electronic literature search was performed using the National Library of Medicine for publications using the keywords genetics of IVDD, lumbar disc degeneration, degenerative disc disease, polymorphisms, SNPs, and disc disease. The articles were then screened based on inclusion criteria that included topics that covered the correlation of SNPs with developing IVDD. Sixty-five articles were identified as containing relevant information. Articles were excluded if they investigated lower back pain or just disc herniation without an analysis of disc degeneration. This study focuses on the chronic degeneration of IVDs. Results Various genes were identified to contain SNPs that influenced the risk of developing IVDD. Among these are genes contributing to structural proteins, such as COL1A1, COL9A3, COL9A3, COL11A1, and COL11A2, ACAN, and CHST3. Furthermore, various SNPs found in the vitamin-D receptor gene are also associated with IVDD. SNPs related to inflammatory cytokine imbalance are associated with IVDD, although some effects are limited by sex and certain populations. SNPs in genes that code for extracellular matrix-degrading enzymes, such as MMP-1, MMP-2, MMP-3, MMP-9, MMP-14, ADAMTS-4, and ADAMTS-5 are also associated with IVDD. Apoptosis-mediating genes, such as caspase 9 gene (CASP9), TRAIL, and death receptor 4 (DR4), as well as those for growth factors, such as growth differentiation factor 5 and VEGF, are identified to have polymorphisms that influence the risk of developing IVDD. Conclusion Within the last 10 years, countless new SNPs have been identified in genes previously unknown to be associated with IVDD. Furthermore, the last decade has also revealed new SNPs identified in genes already known to be involved with increased risk of developing IVDD. Improved understanding of the numerous genetic variants behind various pathophysiological elements of IVDD could help advance personalized care and pharmacotherapeutic strategies for patients suffering from IVDD in the future.

Intraoperative Fluorescence Imaging for Personalized Brain Tumor Resection: Current State and Future Directions

Introduction Fluorescence-guided surgery is one of the rapidly emerging methods of surgical “theranostics.” In this review, we summarize current fluorescence techniques used in neurosurgical practice for brain tumor patients as well as future applications of recent laboratory and translational studies. Methods Review of the literature. Results A wide spectrum of fluorophores that have been tested for brain surgery is reviewed. Beginning with a fluorescein sodium application in 1948 by Moore, fluorescence-guided brain tumor surgery is either routinely applied in some centers or is under active study in clinical trials. Besides the trinity of commonly used drugs (fluorescein sodium, 5-aminolevulinic acid, and indocyanine green), less studied fluorescent stains, such as tetracyclines, cancer-selective alkylphosphocholine analogs, cresyl violet, acridine orange, and acriflavine, can be used for rapid tumor detection and pathological tissue examination. Other emerging agents, such as activity-based probes and targeted molecular probes that can provide biomolecular specificity for surgical visualization and treatment, are reviewed. Furthermore, we review available engineering and optical solutions for fluorescent surgical visualization. Instruments for fluorescent-guided surgery are divided into wide-field imaging systems and hand-held probes. Recent advancements in quantitative fluorescence-guided surgery are discussed. Conclusion We are standing on the threshold of the era of marker-assisted tumor management. Innovations in the fields of surgical optics, computer image analysis, and molecular bioengineering are advancing fluorescence-guided tumor resection paradigms, leading to cell-level approaches to visualization and resection of brain tumors.

Preoperative estimation of disc herniation recurrence after microdiscectomy: predictive value of a multivariate model based on radiographic parameters

BACKGROUND CONTEXT Recurrence of lumbar disc herniation (rLDH) is one of the unfavorable outcomes after microdiscectomy. Prediction of the patient population with increased risk of rLDH is important because patients may benefit from preventive measures or other surgical options. PURPOSE The study assessed preoperative factors associated with rLDH after microdiscectomy and created a mathematical model for estimation of chances for rLDH. STUDY DESIGN/SETTING This is a retrospective case-control study. PATIENT SAMPLE The study includes patients who underwent microdiscectomy for LDH. OUTCOME MEASURES Lumbar disc herniation recurrence was determined using magnetic resonance imaging. METHODS The study included 350 patients with LDH and a minimum of 3 years of follow-up. Patients underwent microdiscectomy for LDH at the L4-L5 and L5-S1 levels from 2008 to 2012. Patients were divided into two groups to identify predictors of recurrence: those who developed rLDH (n=50) within 3 years and those who did not develop rLDH (n=300) within the same follow-up period. Multivariate analysis was performed using patient baseline clinical and radiography data. Non-linear, multivariate, logistic regression analysis was used to build a predictive model. RESULTS Recurrence of LDH occurred within 1 to 48 months after microdiscectomy. Preoperatively, patients who developed rLDH were smokers (70% vs. 27%, p<.01; odds ratio [OR]=6.31, 95% confidence interval [CI]: 3.27-12.16) and had higher body mass index (29.0±6.1 vs. 27.0±4.3, p=.03; OR=1.09 per 0.01 unit change). Radiological parameters that were associated with rLDH were higher disc height index (0.35±0.007 vs. 0.26±0.002, p<.001), higher segmental range of motion (9.8±0.28° vs. 7.6±0.11°, p<.001; OR=0.53 per 0.01 unit change), and lower central angle of lumbar lordosis (33.4±0.81° vs. 47.1±0.47°, p<.001; OR=0.53 per 0.01 unit change). Additionally, Pfirrmann grade 3 (OR=16.62, 95% CI: 8.10-34.11), protrusion type of LDH (OR=5.90, 95% CI: 3.06-11.36), and Grogan sclerosis grades 3 and 4 (OR=4.81, 95% CI: 2.50-9.22) were also associated with rLDH. Multivariate non-linear modeling allowed for more accurate prediction of rLDH (90% correct prediction of rLDH; 99% correct prediction of no rLDH) than other univariate logit models. CONCLUSIONS Preoperative radiographic parameters in patients with LDH can be used to assess the risk of recurrence after microdiscectomy. The multifactorial non-linear model provided more accurate rLDH probability estimation than the univariate analyses. The software developed from this model may be implemented during patient counseling or decision making when choosing the type of primary surgery for LDH.

Prospective Comparison of Microsurgical, Tubular-Based Endoscopic, and Endoscopically Assisted Diskectomies: Clinical Effectiveness and Complications in Railway Workers

OBJECTIVE Although endoscopic diskectomy is superior to microsurgical diskectomy in terms of incision size, postoperative pain, and cosmetic appeal, the effectiveness and indications for endoscopic versus microsurgical diskectomy remain active discussion topics. Because of the increasing incidence of diskectomies being performed in Russia, further assessment of these techniques is needed. We performed a comparative analysis of 1-year clinical results and complications of microsurgical, tubular-based interlaminar endoscopic, and endoscopically assisted microsurgical diskectomies for patients with herniated lumbar disks. METHODS The patient cohort included 131 patients who were enrolled in a prospective, randomized controlled study and 617 patients for whom data were gathered retrospectively. The quality of life was assessed using the Oswestry Disability Index (version 2.1a) and pain severity was analyzed using the visual analog scale for pain preoperatively, at discharge, and at 3, 6, and 12 months postoperatively. RESULTS Microsurgical, tubular-based endoscopic, and endoscopically assisted microsurgical diskectomies were all effective in relieving acute radicular symptoms. Recurrent disk herniation occurred more frequently after tubular-based endoscopic diskectomy than after the other approaches. CONCLUSIONS Our findings indicate that these 3 surgical techniques are highly effective and have similar clinical results at 1-year follow-up. Although this study points to differences in complications resulting from the 3 techniques, larger prospective studies are needed to more definitively assess possible surgical differences, complications, and outcomes. The endoscopically assisted diskectomy technique allows for minimally invasive surgery and offers enhanced visualization of the anatomy that is hidden from view in microscopic procedures.

Off-the-Job Microsurgical Training on Dry Models: Siberian Experience

BACKGROUND Microsurgical training has become an obligatory part of many neurosurgical training programs. OBJECTIVE To assess the cost and effectiveness of acquiring and maintaining microneurosurgical skills by training on an off-the-job basis using dry models. METHODS A dry off-the-job microneurosurgical training module was set up. Training exercises involved microdissection in a deep operation field, suturing and tying on gauze, untying, pushing of thread end, and microanastomosis. The time to complete the task and success rate were evaluated. The total cost of all necessary equipment and expendables for the training module was US

Maxillary Artery to Middle Cerebral Artery Bypass: A Novel Technique for Exposure of the Maxillary Artery

910. RESULTS Fifteen residents participated in the continuous off-the-job training. The average time taken to perform the anastomosis decreased after the month of training from 90 to 20 minutes. Authors revealed that at 2 months, the total time and time to complete anastomosis increased significantly for the participants who discontinued practice after the first month, compared with those who just practiced suturing on gauze after the first month (P < 0.01). The average Northwestern Objective Microanastomosis Assessment Tool score was 36 for novice and 65 for experienced participants. CONCLUSION The dry off-the-job training showed to be readily available and can be helpful for microsurgical training in the low-income regions of the world. Our data suggest that microsurgical training should be continuous and repetitive. Simulation training may benefit from models for repetitive training of relevant technical part-skills.

The Role of Bone Morphogenetic Proteins 2, 7, and 14 in Approaches for Intervertebral Disk Restoration

OBJECTIVE To define the maxillary artery (MaxA) anatomy and present a novel technique for exposing and preparing this vessel as a bypass donor. METHODS Cadaveric and radiologic studies were used to define the MaxA anatomy and show a novel method for harvesting and preparing it for extracranial to intracranial bypass. RESULTS The MaxA runs parallel to the frontal branch of the superficial temporal artery and is located on average 24.8 ± 3.8 mm inferior to the midpoint of the zygomatic arch. The pterygoid segment of the MaxA is most appropriate for bypass with a maximal diameter of 2.5 ± 0.4 mm. The pterygoid segment can be divided into a main trunk and terminal part based on anatomic features and use in the bypass procedure. The main trunk of the pterygoid segment can be reached extracranially, either by following the deep temporal arteries downward toward their origin from the MaxA or by following the sphenoid groove downward to the terminal part of the pterygoid segment, which can be followed proximally to expose the entire MaxA. In comparison, the prebifurcation diameter of the superficial temporal artery is 1.9 ± 0.5 mm. The average lengths of the mandibular and pterygoid MaxA segments are 6.3 ± 2.4 and 6.7 ± 3.3 mm, respectively. CONCLUSIONS The MaxA can be exposed without zygomatic osteotomies or resection of the middle fossa floor. Anatomic landmarks for exposing the MaxA include the anterior and posterior deep temporal arteries and the pterygomaxillary fissure.

Improving utility of brain tumor confocal laser endomicroscopy: objective value assessment and diagnostic frame detection with convolutional neural networks

Bone morphogenetic proteins (BMPs) are a group of cytokines in the transforming growth factor beta superfamily. Transforming growth factor beta originally was described as a group of substances that have the ability to produce exostosis formation, but it was later discovered to have a wide range of chondroinductive and osteoinductive actions during embryogenesis and later in life. Recombinant BMPs were successfully introduced into clinical practice for augmentation of bone fusion in spinal and orthopedic surgeries; however, BMPs are now gaining attention from researchers for their role in intervertebral disk (IVD) pathology. We summarize the current understanding and future directions for the role of BMPs in IVD degradation and restoration. Recombinant human BMP-2, a component of INFUSE bone graft (Medtronic, Minneapolis, Minnesota, USA), was the first clinically available BMP drug. INFUSE bone grafts are used to enhance bone formation in lumbar fusion procedures, decreasing the rate of nonunions compared with autologous iliac crest bone grafts. It is also approved by the U.S. Food and Drug Administration for several other bone fusion procedures. Initial studies for BMP-2 in the IVD showed regenerative potential in the nucleus pulposus, where BMP2 resulted in a mitogenic effect and stimulated proteoglycan synthesis without ossification; additionally, studies in explanted rabbit IVDs showed that the presence of BMP-2 favorably increased expression of collagen II and aggrecans, while decreasing expression of catabolic matrix metalloproteinases in the anulus fibrosus. However, BMP-2 also decreased glycosaminoglycan content and increased type I collagen production in the nucleus pulposus as well as initiating ossification of the anulus fibrosus. Furthermore, exogenous application of BMP-2 can accelerate osteophyte formation, typically seen clinically in late-stage degenerative disk disease as a compensatory mechanism for spinal instability. Endogenous BMP-2 in the IVD increases with age and in mechanically induced models of disk degeneration. Recombinant human BMP-7, also known as osteogenic protein1, is currently marketed as OP-1 (Stryker Biotech, Hopkinton, Massachusetts, USA), an aid for posterior spinal fusion and long