[Innovations in Combined Surgery of Endoscopic Transsphenoidal Surgery and Craniotomy].

Combined endoscopic transsphenoidal surgery and craniotomy may be useful for tumors extending into the suprasellar region or ventricles and for tumors extending simultaneously into the nasal sinuses and intracranial space. This method allows two surgeons to share the surgical field while compensating for each other's blind spots and allows for safe tumor removal by separating the normal structure from the tumor and protecting the normal structure. Simultaneous combined endoscopic transsphenoidal surgery and craniotomy require a lot of equipment; however, by devising the layout of the equipment in the operating room, the staff involved in the surgery can perform their roles more effectively. However, this method results in extensive dural and cranial defects, and prevention of cerebrospinal fluid leakage and perioperative surgical site infection is essential. Skull base reconstruction using autologous tissues and medical materials at appropriate locations can reduce the risk of postoperative cerebrospinal fluid leakage and surgical site infection. Furthermore, multilayered reconstruction using restorative medical materials eliminates the need for autologous tissue, is minimally invasive, shortens the operative time, reduces postoperative stress, and shortens the length of hospital stay. A combination of endoscopic transsphenoidal surgery and craniotomy will contribute to the improvement of the safety of highly difficult tumorectomies under a reliable skull base reconstruction method.

Surgical management of skull base meningiomas and vestibular schwannomas.

PURPOSE OF REVIEW: The aim of this study is to discuss surgical management of meningiomas and schwannomas of skull base. RECENT FINDINGS: Meningiomas and schwannomas are typically benign neoplasm with a good prognosis after surgery. Patients should be treated individually related to several features: size and localization of tumor and its proximity with deep critical neurovascular structures, neurological status, age and comorbidity. Also, the widespread use of neuroimaging and the progressive and constant aging of the populations inevitably result in the increase of detection rate of incidental (asymptomatic) neoplasm.Nowadays, there are still controversies about the correct management strategy. SUMMARY: Surgery represents the gold standard treatment, with the objective of gross total resection; however, it is not always feasible due to localization, encasement of neuro-vascular structure, invasion of cranial nerve and brain parenchyma. Stereotactic radiosurgery and radiation therapy are important to achieve a satisfactory functional outcome and tumor control in case of residue or recurrence. A multidisciplinary approach is pivotal.

Migration Capacity of Stem Cells from Human Exfoliated Deciduous Teeth Towards Glioma.

BACKGROUND: Stem cells from human exfoliated deciduous teeth (SHED) are a mesenchymal stem cell type and have recently attracted attention for their high proliferative rate, multipotency, and immunosuppressive properties. However, SHED have not yet been investigated for anticancer properties. We therefore investigated whether SHED can be used as a treatment modality, particularly for anti-glioma therapy. METHODS: In vitro, we examined the mobility of SHED and their ability to migrate towards glioma-conditioned medium and specific growth factors secreted by malignant gliomas. In vivo, we transplanted SHED into the left hemisphere of nude mice that had been previously implanted with human malignant glioma U87 cells into the right hemisphere. We assessed whether SHED had tumorigenic potential. RESULTS: SHED exhibited strong migration ability towards malignant glioma in both in vitro and in vivo assays. In vitro, SHED migrated towards glioma-conditioned medium and specific growth factors such as stem cell factor, platelet-derived growth factor BB, C-X-C motif chemokine ligand 12, and vascular endothelial growth factor. SHED were accumulated around tumor cells in the contralateral hemisphere 1 week after transplantation. Moreover, SHED remained in the brains of nude mice 150 days after transplantation. Finally, we verified that SHED had no malignant transformation or engraftment of SHED in the mouse brain. CONCLUSIONS: Our findings indicate that SHED can potentially be applied to track malignant glioma.

Largest neurosurgical social media group and its impact on communication and research.

BACKGROUND: The use of social media to communicate and disseminate knowledge has increased exponentially, especially in the field of neurosurgery. 'Neurosurgery cocktail' (NC) was developed by a group of young neurosurgeons as a means of sharing didactic materials and clinical experiences via social media. It connects 35.000 neurosurgeons worldwide on multiple platforms, primarily Facebook and Twitter. Given the rising utilization of social media in neurosurgery, the popularity of NC has also increased since its inception. In this study, the authors surveyed the social media analytics of NC for both Facebook and Twitter. Besides, we reviewed the literature on the use of social media in neurosurgery. METHODS: Facebook and Twitter metrics were extracted through each respective platform's analytics tools from December 2020 (earliest available date for data analysis) through January 2021. A literature search was conducted using PubMed (MEDLINE) and Scopus databases. RESULTS: On Facebook, as of January 2021, the group had a total of 25.590 members (87.6% male), most commonly (29%) between 35 and 44 years of age with over 100 countries were represented. As of January 2021, they had amassed 6457 followers on Twitter. During the last 28 d between December 2020 and January 2021, the account published 65 tweets that garnered a total of 196,900 impressions. Twelve articles were identified in our literature review on the use of social media within the neurosurgical community. CONCLUSIONS: NC is one of the most widely utilized neurosurgical social media resources available. Sharing knowledge has been broadened thanks to the recent social media evolution, and NC has become a leading player in disseminating neurosurgical knowledge.

Development of a novel gripping test for the evaluation of the finger fine motor ability in MPTP-treated monkeys.

Assessing the finger fine motor ability is extremely important. However, conventional behavioral tests in monkeys are complicated and costly. We attempted to develop a new task to assess the precise finger grip in Parkinson's disease monkeys based on the principles of objectification, multipurpose, and simplification. This study involved seven adult male cynomolgus monkeys. A gripping test based on the previous food reaching test was developed. Parallel experiments of food reaching test and gripping test affected by the treatments of levodopa and deep brain stimulation of the subthalamic nucleus were performed to verify the utility of the gripping test. We found that gross motor ability (measured by food reaching test) could be significantly improved by both the subthalamic nucleus and levodopa administration, which reproduced the results of our previous study. The finger fine motor ability (measured by the gripping test) could be significantly improved by levodopa administration, but not by the subthalamic nucleus. Our results verified the utility and reliability of the gripping test, which is a simple, convenient, and objective task for evaluating the finger fine motor skill in Parkinson's disease monkeys. Mechanisms of the efficacy of deep brain stimulation on fine motor ability require further investigation.

Detailed anatomy knowledge: first step to approach petroclival meningiomas through the petrous apex. Anatomy lab experience and surgical series.

Petroclival meningiomas are a challenge for neurosurgeons due to the complex anatomy of the region that is rich of vessels and nerves. A perfect and detailed knowledge of the anatomy is very demanding in neurosurgery, especially in skull base surgery. The authors describe the microsurgical anatomy to perform an anterior petrosectomy based on their anatomical and surgical experience and perform a literature review. The temporal bone is the most complex and fascinating bone of skull base. The apex is located in the angle between the greater wing of the sphenoid and the occipital bone. Removing the petrous apex exposes the clivus. The approach directed through the temporal bone in this anatomical area is referred to as an anterior petrosectomy. The area that must be drilled is the rhomboid fossa that is defined by the Kawase, premeatal, and postmeatal triangles. In Division of Neurosurgery - University of Turin, 130 patients, from August 2013 to September 2015, underwent surgical resection of intracranial meningiomas. In this group, we have operated 7 PCMs and 5 of these were approached performing an anterior petrosectomy with good results. In our conclusions, we feel that this surgery require an advanced knowledge of human anatomy and a specialized training in interpretation of radiological and microsurgical anatomy both in the dissection lab and in the operating room.

Pseudo-continuous arterial spin labeling reflects vascular density and differentiates angiomatous meningiomas from non-angiomatous meningiomas.

Pseudo-continuous arterial spin labeling (PCASL) can measure tumor blood flow (TBF) reliably. We investigated meningioma TBF using PCASL and assessed for any correlation with histopathological microvascular density (MVD) and the World Health Organization (WHO) classification. Conventional MRI with contrast T1-weighted images and PCASL were acquired with a 3 T scanner before surgery in 25 consecutive patients with meningiomas. Using the PCASL perfusion map, the mean and maximum TBF were calculated from regions of interest placed in the largest cross-sectional plane of each tumor. Tissue sections from 16 patients were stained with CD31 to evaluate MVD and were assigned a WHO classification. The TBFs were statistically compared with MVD and the histopathological meningioma subtypes. There were 16 meningothelial meningiomas, four angiomatous meningiomas, two fibrous meningiomas, one transitional meningioma, and two atypical meningiomas. We observed significant correlation between MVD and both mean and maximum TBF (p < 0.05). The mean and maximum TBF ((mean)TBF, (max)TBF) in angiomatous meningiomas are significantly higher than that in non-angiomatous meningiomas (p < 0.05). PCASL is useful in assessing meningioma vascularity, and in differentiating angiomatous meningiomas from non-angiomatous meningiomas.

Ipsilateral sensorimotor deficits in lateral medullary infarction: a case report.

The patient, a 32-year-old man, presented with sudden onset of occipital headache, vertigo, dysarthria, gait ataxia, right Horner syndrome, numbness of the right hand, and mild right hemiparesis. On magnetic resonance imaging, an acute small infarction was located on the right side of the caudal medulla extending dorsomedially. Magnetic resonance angiography showed severe right vertebral artery stenosis. Lateral medullary infarction associated with ipsilateral sensorimotor deficits in the limb is very rare, and the lesion probably involved the ipsilateral dorsal column or decussating lemniscal fibers and corticospinal fibers caudal to the pyramidal decussation or compression of the decussation.

Cavernous Sinus Meningioma of the Oculomotor Nerve in a Child: A Surgical Case Study.

Pediatric cavernous sinus meningiomas are rare. Herein, we present the case of a 5-year-old boy who presented with progressive left oculomotor nerve palsy. A head magnetic resonance imaging revealed a mass lesion in the left cavernous sinus, following which tumor resection was performed. The tumor strongly adhered to the left oculomotor nerve without adherence to the walls of the cavernous sinus; however, its border with the nerve was unclear. Histopathological analysis led to the diagnosis of fibrous meningioma. To the best of our knowledge, this is the first case study to report the pediatric development of a cavernous sinus meningioma in the oculomotor nerve.

Potent bystander effect and tumor tropism in suicide gene therapy using stem cells from human exfoliated deciduous teeth.

Herpes simplex virus thymidine kinase (HSVTK)/ganciclovir (GCV) suicide gene therapy has a long history of treating malignant gliomas. Recently, stem cells from human exfoliated deciduous teeth (SHED), which are collected from deciduous teeth and have excellent harvestability, ethical aspects, and self-renewal, have been attracting attention mainly in the field of gene therapy. In the present study, we assessed SHED as a novel cellular vehicle for suicide gene therapy in malignant gliomas, as we have previously demonstrated with various cell types. SHED was transduced with the HSVTK gene (SHEDTK). In vitro experiments showed a significant bystander effect between SHEDTK and glioma cell lines in coculture. Furthermore, apoptotic changes caused by caspase 3/7 activation were simultaneously observed in SHEDTK and glioma cells. Mice implanted with a mixture of U87 and SHEDTK and treated with intraperitoneal GCV survived for longer than 100 days. Additionally, tumors in treatment model mice were significantly reduced in size during the treatment period. SHEDTK implanted at the contralateral hemisphere migrated toward the tumor crossing the corpus callosum. These results suggested that SHEDTK-based suicide gene therapy has potent tumor tropism and a bystander-killing effect, potentially offering a new promising therapeutic modality for malignant gliomas.

Efficacy of HSV-TK/GCV system suicide gene therapy using SHED expressing modified HSV-TK against lung cancer brain metastases.

Lung cancer is one of the most common cancers, and the number of patients with intracranial metastases is increasing. Previously, we developed an enzyme prodrug suicide gene therapy based on the herpes simplex virus thymidine kinase (HSV-TK)/ganciclovir (GCV) system using various mesenchymal stem cells to induce apoptosis in malignant gliomas through bystander killing effects. Here, we describe stem cells from human exfoliated deciduous teeth (SHED) as gene vehicles of the TK/GCV system against a brain metastasis model of non-small cell lung cancer (NSCLC). We introduced the A168H mutant TK (TKA168H) into SHED to establish the therapeutic cells because of the latent toxicity of wild type. SHED expressing TKA168H (SHED-TK) exhibited chemotaxis to the conditioned medium of NSCLC and migrated toward implanted NSCLC in vivo. SHED-TK demonstrated a strong bystander effect in vitro and in vivo and completely eradicated H1299 NSCLC in the brain. SHED-TK cells implanted intratumorally followed by GCV administration significantly suppressed the growth of H1299 and improved survival time. These results indicate that the TKA168H variant is suitable for establishing therapeutic cells and that intratumoral injection of SHED-TK followed by GCV administration may be a useful strategy for therapeutic approaches.

Epidemiology of human papillomavirus genotypes in pregnant Japanese women.

To investigate the pre-vaccination epidemiology of genital human papillomavirus (HPV) infections and genotypes in pregnant Japanese women, we performed Pap smear tests and HPV genotype testing in patients attending Nagasaki University Hospital and collaborating hospitals from August 2007 to July 2010. Serial uterine cervical specimens were obtained from 151 pregnant women. The HPV test was positive on the first visit in 54 women (35.8%; 54/151, average age 30). A total of 49 women (32.5%; 49/151) were infected by at least one high-risk HPV and 5 women were infected by only low-risk HPV. The three most prevalent high-risk HPV genotypes were HPV 52 (31.5%; 17/54), HPV 16 (29.6%; 16/51) and HPV 31 (13.0%; 7/51). The HPV infection pattern (negative, single infection and multiple infection) differed significantly according to the pregnancy trimester (χ(2)-test; P<0.01(Pearson)). Among HPV-infected pregnant Japanese women, HPV52 was the most common genotype. The second most common genotype was HPV16, and these two genotypes accounted for ∼60% of HPV-positive pregnant women. Infection with multiple HPV genotypes was observed more frequently in the first trimester of pregnancy and the pattern of infection changed significantly depending on pregnancy stage.

Synthetic emmprin peptides with chitobiose substitution stimulate MMP-2 production by fibroblasts.

BACKGROUND: Emmprin, a glycoprotein containing two Ig domains, is enriched on tumor cell surfaces and stimulates matrix metalloproteinase (MMP) production by adjacent stromal cells. Its first Ig domain (ECI) contains the biologically active site. The dependence of emmprin activity on N-glycosylation is controversial. We investigated whether synthetic ECI with the shortest sugar is functionally active. METHODS: The whole ECI peptides carrying sugar chains, a chitobiose unit or N-linked core pentasaccharide, were synthesized by the thioester method and added to fibroblasts to examine whether they stimulate MMP-2 production. RESULTS: ECI carrying a chitobiose unit, ECI-(GlcNAc) 2, but not ECI without a chitobiose unit or the chitobiose unit alone, dose-dependently stimulated MMP-2 production by fibroblasts. ECI with longer chitobiose units, ECI-[(Man)3(GlcNAc)2], also stimulated MMP-2 production, but the extent of its stimulation was lower than that of ECI-(GlcNAc)2. CONCLUSIONS: Our results indicate that ECI can mimic emmprin activity when substituted with chitobiose, the disaccharide with which N-glycosylation starts.

Reinforcement of pericranium as a dural substitute by fibrin sealant.

BACKGROUND: For dural plasty, several kinds of substitute materials are used clinically. Among these materials, pericranium is often used as a dural substitute since it is autologous and easy to harvest. However, it is rather thin and fragile, which makes it difficult to suture onto peripheral dura mater, especially when the defect is large. OBJECTIVE: We present a simple method of reinforcing the pericranium with fibrin sealant, which facilitates easier handling and suturing of the pericranium. METHODS: Fifteen patients who underwent surgical removal of meningioma, metastatic brain tumor and glioma attached to the dura mater were included in this analysis. To close the defects, we use 'fibrin-sealed pericranium'. Herein we describe the method we employed in these cases. First, a standard skin flap is made by dissecting the subgaleal layer, leaving the periosteum on the bone. Second, fibrin sealant is evenly applied to the pericranium. Finally, the pericranium is cut along the reinforced area and dissected from the bone. The harvested pericranium is then used for closure of the dural defect. Some of these patients received further treatment as needed according to each pathology. The fibrin-sealed pericranium was examined histopathologically. RESULTS: Fibrin-sealing of pericranium made it durable enough to be handled and sutured easily. There were no significant complications or treatment failures, such as infection or CSF leakage. CONCLUSIONS: Reinforcement of the pericranium with fibrin sealant is a simple and easy method to reduce the stress of dural plasty.

Pre-vaccination epidemiology of human papillomavirus infections in Japanese women with abnormal cytology.

AIM: To investigate the pre-vaccination epidemiology of genital human papillomavirus (HPV) infections and genotypes in women with abnormal cytology in Nagasaki, Japan. MATERIAL AND METHODS: We performed Pap smear tests, biopsies and HPV genotype testing in Nagasaki Prefecture from August 2007 through November 2009. RESULTS: During the study period, serial samples of uterine cervical specimens were obtained from 539 subjects with abnormal cytology and/or squamous intraepithelial lesions (SIL) confirmed previously, or with clinically suspected invasive cervical cancer. In 119 HPV-positive subjects with low-grade SIL, the three most prevalent high-risk HPV genotypes were HPV52 (21.8%; 26/119), HPV16 (20.2%; 24/119) and HPV56 (17.6%; 21/119). In 199 women, 127 HPV-positive subjects with high-grade SIL and 67 HPV-positive subjects with squamous cell carcinoma (SCC), the three most prevalent high-risk HPV genotypes were HPV16 (44.3%; 86/194), HPV52 (20.6%; 40/194) and HPV58 (16.0%; 31/194). CONCLUSION: Compared with the distribution of high-risk HPV genotypes in other countries, HPV52 was a more common genotype in Nagasaki. With disease progression to SCC, the distribution of high-risk HPV56 belonging to the A6 HPV family decreased, while HPV16 and HPV52 belonging to the A9 HPV family persisted. Our data provide an important resource to address the case for vaccination against HPV genotypes other than HPV16 and HPV18 in Japan.

A novel technique for fence-post tube placement in glioma using the robot-guided frameless neuronavigation technique under exoscope surgery: patient series.

BACKGROUND: Robotic technology is increasingly used in neurosurgery. The authors reported a new technique for fence-post tube placement using robot-guided frameless stereotaxic technology with neuronavigation in patients with glioma. OBSERVATIONS: Surgery was performed using the StealthStation S8 linked to the Stealth Autoguide cranial robotic guidance platform and a high-resolution three-dimensional (3D) surgical microscope. A surgical plan was created to determine the removal area using fence-post tube placement at the tumor and normal brain tissue boundary. Using this surgical plan, the robotic system allowed quick and accurate fence-post tube positioning, automatic alignment of the needle insertion and measurement positions in the brain, and quick and accurate puncture needle insertion into the brain tumor. Use of a ventricular drainage tube for the outer needle cylinder allowed placement of the puncture needle in a single operation. Furthermore, use of a high-resolution 3D exoscope allowed the surgeon to simultaneously view the surgical field image and the navigation screen with minimal line-of-sight movement, which improved operative safety. The position memory function of the 3D exoscope allowed easy switching between the exoscope and the microscope and optimal field of view adjustment. LESSONS: Fence-post tube placement using robot-guided frameless stereotaxic technology, neuronavigation, and an exoscope allows precise glioma resection.

Nicotine does not affect stem cell properties requisite for suicide gene therapy against glioma.

OBJECTIVE:: Glioblastoma is one of the most lethal tumors in adult central nervous system with a median survival of a year and half and effective therapeutic strategy is urgently needed. For that reason, stem cell-based suicide gene therapies have attracted much interest because of potent tumor tropism of stem cells and bystander effect. In this current clinical situation, stem cells are promising delivery tool of suicide genes for glioma therapy. Since habitual cigarette smoking still prevails worldwide, we investigated the effect of nicotine on stem cell tropism toward glioma and gap junctional intercellular communication (GJIC) function between glioma and stem cells, both of which are important for suicide gene therapies. Methods: Mouse induced pluripotent stem cell-derived neural stem cells (iPS-NSCs) and human dental pulp mesenchymal stem cells (DPSCs) were used. The effect of nicotine on tumor tropism to glioma-conditioned medium (CM) at a non-cytotoxic concentration was assessed with Matrigel invasion assay. Nicotine effect on GJIC was assessed with the scrape loading/dye transfer (SL/DT) assay for co-culture of glioma and stem cells and the parachute assay among glioma cells using high-content analysis. Results: Tumor tropism of iPS-NSCs toward GL261-CM and DPSCs toward U251-CM was not affected by nicotine (0.1 and 1 µM). Nicotine at the concentrations equivalent to habitual smoking (1 µM) did not affect GJIC of iPS-NSC/GL261 and DPSC/U251 and GJIC among each glioma cells. Conclusions: The study demonstrated that non-cytotoxic concentrations of nicotine did not significantly change the stem cell properties requisite for stem cell-based suicide gene therapy.

Acute and chronic hemorrhage from radiation-induced cavernous malformation associated with late-delayed radiation necrosis in long surviving glioma patients: A case report.

Although radiation therapy is a standard treatment strategy for patients with glioma, its delayed complications are not clearly understood. Radiation-induced cavernous malformation (RICM) is one of the complications in the delayed phase following radiation therapy, which usually occurs in children. Herein we present three cases of RICM with radiation necrosis in long surviving adult glioma patients, 2 with oligoastrocytoma and one with anaplastic ependymoma. Two of three patients had received an obvious overdose of radiation by additional stereotactic radiation therapy. Repeated episodes of either acute or chronic hemorrhages from RICM worsened the neurological symptoms in all cases. The interval between the last irradiation and the occurrence of symptoms was 45-173 months. The presence of hypointense rim on FLAIR or T2* on magnetic resonance imaging, which resembles the appearance of sporadic cavernous malformations, could be helpful in differentiating RICM from tumor recurrence. Surgical resection was effective in alleviating the symptoms. Microscopically, RICM is a vascular lesion with vulnerable vessels, which are observed in the center of the radiation necrosis. Repeated hemorrhages from these vessels cause either gradual or sudden worsening of neurological symptoms. Therefore, radiation overdose, which results in radiation injury, should be avoided in low grade glioma patients, who could potentially survive for a long period.

Ectopic Relapse of Anti-neutrophil Cytoplasmic Antibody-associated Pituitary Vasculitis with No Elevation of Anti-neutrophil Cytoplasmic Antibodies after Renal Remission.

The relationship between anti-neutrophil cytoplasmic antibody (ANCA) titer levels and relapse risk in patients with ANCA-associated vasculitis (AAV) following clinical remission remains controversial. We herein report a case showing ectopic relapse of AAV in the pituitary with no ANCA elevation after renal remission. Magnetic resonance imaging revealed an enlarged pituitary gland. A pituitary biopsy showed geographic necrosis with multinucleated giant cells. We diagnosed this case as relapse of AAV in the pituitary. One month after rituximab therapy, the pituitary gland volume had decreased. The intensification of therapy due to the possibility of vasculitis relapse may facilitate better control of AAV.

Cosmetic and Neuroprotective Placement of Custom-Made Ultra-High-Molecular-Weight Polyethylene Cranial Plate (SKULPIO) in Single-Step Surgery: Technical Note and Case Report.

BACKGROUND: Cranioplasty is a common procedure in neurosurgery. However, cosmetic and neuroprotective reconstructions are necessary after cranioplasty. Treatment of patients with a meningioma with bone infiltration requires removal of the tumor-infiltrated bone and subsequent cranioplasty. We report an efficient technique for cosmetic and neuroprotective reconstructions using a custom-made ultra-high-molecular-weight polyethylene cranial plate (SKULPIO, Kyocera Medical, Kyoto, Japan) in a single-step surgery involving tumor removal and skull reconstruction. METHODS: We present 2 illustrative cases of a 49-year-old female with a right frontal convexity meningioma and 69-year-old male with a bilateral parasagittal atypical meningioma, both involving extensive skull invasion. We preoperatively planned craniotomy size to facilitate the removal of the tumor-infiltrated skull bone using the patients' 3-dimensional cranial models followed by the construction of a custom-made cranial plate. After tumor removal, we drilled out the outer table and the diploe of the cranial edge until the custom-made bone plate accurately fit the bone defect. Finally, the cranial plate was fixed using titanium plates and screws. RESULTS: Postoperative magnetic resonance imaging for each case revealed total meningioma removal and an aesthetically reconstructed skull. Using this technique, precise adjustment of the cranial edge to the plate contributes to a gapless and aesthetic reconstruction. Furthermore, the intact inner table of the skull firmly supports the custom-made bone plate. CONCLUSIONS: This technique involving the placement of a custom-made cranial plate during a single-step surgery was found to be efficient for cosmetic and neuroprotective reconstructions.