[Preoperative Simulation of Endoscopic Endonasal Approach for Craniopharyngiomas or Tuberculum Sellae Meningiomas].

Preoperative simulation for endoscopic endonasal approach(EEA)using computed tomography and magnetic resonance imaging evaluates tumor extension and the relationship between adjacent structure(the pituitary stalk, major vessels, and cranial nerves); therefore, preoperative planning of nasal procedure, skull base bony removal, and cranial base reconstruction are possible. Additionally, three-dimensional(3D)fusion image aids surgeons to visualize intraoperative 3D findings. These preoperative simulations are critical to avoid complications and predict pitfalls perioperatively. However, tumor consistency or adhesion with adjacent structure cannot be predicted but is judged perioperatively, which affects the extent of tumor resection. This manuscript describes important points of preoperative simulation for EEA, especially the transplanum-transtuberculum approach for craniopharyngiomas or tuberculum sellae meningiomas, showing some examples in patients.

Rise of oligodendroglioma hypermutator phenotype from a subclone harboring TP53 mutation after TMZ treatment.

Oligodendrogliomas characterized and defined by 1p/19q co-deletion are slowly growing tumors showing better prognosis than astrocytomas. TP53 mutation is rare in oligodendrogliomas while the vast majority of astrocytomas harbor the mutation, making TP53 mutation mutually exclusive with 1p/19q codeletion in lower grade gliomas virtually. We report a case of 51-year-old woman with a left fronto-temporal oligodendroglioma that contained a small portion with a TP53 mutation, R248Q, at the initial surgery. On a first, slow-growing recurrence 29 months after radiation and nitrosourea-based chemotherapy, the patient underwent TMZ chemotherapy. The recurrent tumor responded well to TMZ but developed a rapid progression after 6 cycles as a malignant hypermutator tumor with a MSH6 mutation. Most of the recurrent tumor lacked typical oligodendroglioma morphology that was observed in the primary tumor, while it retained the IDH1 mutation and 1p/19q co-deletion. The identical TP53 mutation observed in the small portion of the primary tumor was universal in the recurrence. This case embodied the theoretically understandable clonal expansion of the TP53 mutation with additional mismatch repair gene dysfunction leading to hypermutator phenotype. It thus indicated that TP53 mutation in oligodendroglioma, although not common, may play a critical role in the development of hypermutator after TMZ treatment.

Risk Factors for Radiation Necrosis and Local Recurrence after Proton Beam Therapy for Skull Base Chordoma or Chondrosarcoma.

[Proposal] Here, we retrospectively evaluate risk factors for radiation necrosis and local recurrence after PBT for skull base chordoma or chondrosarcoma. [Patients and Methods] We analyzed 101 patients who received PBT for skull base chordomas and chondrosarcomas from January 1989 to February 2021. Multivariable logistic regression models were applied for local recurrence, temporal lobe radiation necrosis rates, and temporal lobe radiation necrosis. [Results] In multivariate analysis, chordoma and large tumor size were independent significant factors for local recurrence. The 1-, 2-, 3-, 4- and 5-year local recurrence rates were 3.9%, 16.9%, 20.3%, 28.5% and 44.0% for chordoma and 0%, 0%, 0%, 0% and 7.1% for chondrosarcoma, respectively. The local recurrence rates of small tumors (<30 mm) were 4.3%, 14.7%, 17.7%, 17.7% and 25.9%, and those for large tumors were 3.6%, 15.1%, 19.2%, 32.7% and 59.6%, respectively. In multivariate analysis, BED Gy10 and total dose were risk factors for radiation necrosis. [Conclusions] For skull base chordoma and chondrosarcoma, the risk factors of local recurrence were chordoma and large tumor size, and those of radiation necrosis were BED Gy10 and total dose, respectively. DVH analysis is needed to investigate the risk factors for brain necrosis in more detail.

Academic Activities of Female Neurosurgeons in All Branch Meetings of the Japan Neurosurgical Society.

This study aims to evaluate the academic activities of female neurosurgeons at all branch meetings of the Japan Neurosurgical Society and identify related issues they encountered. The programs of all seven branch meetings of the Japan Neurosurgical Society (Hokkaido, Tohoku, Kanto, Chubu, Kinki, Chugoku/Shikoku, and Kyushu) were used to determine the number of presentations and chairpersons by sex. The covered period was from January 2008 to December 2020, which was available for viewing during the survey. Of note, only the Kinki branch used data from January 2008 to December 2019. The Neurologia Medico-chirurgica (NMC), the journal of the Japan Neurosurgical Society, was also reviewed to identify publication achievements during the same period. In all seven branches, the percentage of presentations given by female physicians increased from 7.9% in 2008 to 9.6% in 2020 (p < 0.05).Conversely, the percentage of female chairpersons in all branch meetings did not change over time and it was significantly lower (1.1%) than that of female presenters (7.9%) for all branch meetings combined in over 13 years (p < 0.01). In the NMC, the number of articles with female physicians as first authors did not increase or decrease over the years. We conclude that efforts to smoothly promote female neurosurgeons as chairpersons and increase the number of female first authors are necessary to facilitate their academic activities.

[Epidemiology, Genetics and Pathophysiology of Pituitary Tumors].

Pituitary tumors or tumors of the sella turcica include pituitary neuroendocrine tumors, Rathke's cleft cysts, craniopharyngiomas, tuberculum sellae, planum sphenoidale meningiomas, germ cell tumors, and hypophysitis. In addition, some rare tumors, such as pituicytomas, granular cell tumors, spindle cell oncocytomas, and chordomas or chondrosarcomas, arise from the parasellar regions. The treatment strategy is completely different for each lesion; therefore, accurate diagnosis is essential.

Differentiation of silent corticotroph pituitary neuroendocrine tumors (PitNETs) from non-functioning PitNETs using kinetic analysis of dynamic MRI.

PURPOSE: Silent corticotroph pituitary adenomas (SCAs)/pituitary neuroendocrine tumors (PitNETs) are common non-functioning pituitary adenomas (NFAs)/PitNETs with a clinically aggressive course. This study aimed to investigate the ability of time-intensity analysis of dynamic magnetic resonance imaging (MRI) for distinguishing adrenocorticotropic hormone (ACTH)-positive SCAs and ACTH-negative SCAs from other NFAs. MATERIALS AND METHODS: We retrospectively evaluated the dynamic MRI findings of patients with NFAs. The initial slope of the kinetic curve (slopeini) obtained by dynamic MRI for each tumor was analyzed using a modified empirical mathematical model. The maximum slope of the kinetic curve (slopemax) was obtained by geometric calculation. RESULTS: A total of 106 patients with NFAs (11 ACTH-positive SCAs, 5 ACTH-negative SCAs, and 90 other NFAs) were evaluated. The kinetic curves of ACTH-positive SCAs had significantly lesser slopeini and slopemax compared with ACTH-negative SCAs (P = 0.040 and P = 0.001, respectively) and other NFAs (P = 0.018 and P = 0.035, respectively). Conversely, the slopeini and slopemax were significantly greater in ACTH-negative SCAs than in NFAs other than ACTH-negative SCAs (P = 0.033 and P = 0.044, respectively). In receiver operating characteristic analysis of ACTH-positive SCAs and other NFAs, the area under the curve (AUC) values for slopeini and slopemax were 0.762 and 0748, respectively. In predicting ACTH-negative SCAs, the AUC values for slopeini and slopemax were 0.784 and 0.846, respectively. CONCLUSIONS: Dynamic MRI can distinguish ACTH-positive SCAs and ACTH-negative SCAs from other NFAs.

Endoscopic transoral resection for an upper cervical chordoma in a pediatric patient.

BACKGROUND: Upper cervical chordoma (UCC) is a rare disease, and although transoral approaches are the methods of choice, minimally invasive techniques have not been established. METHOD: We report the successful use of endoscopic transoral surgery for upper cervical chordoma at the C1-3 levels in the midline epidural space in an 8-year-old girl who presented with neck pain and quadriplegia. Three months after occipitocervical posterior fixation, endoscopic transoral surgery was performed and the tumor was nearly totally removed. CONCLUSION: Endoscopic transoral surgery in pediatric patients with UCCs is a minimally invasive and safe technique.

Successful Treatment of Basaloid Squamous Cell Carcinoma of the Nasal Cavity With Brain Invasion.

Basaloid squamous cell carcinoma (BSCC) is a rare and aggressive subtype of squamous cell carcinoma (SCC). To date, no consensus on the treatment of BSCC has been established yet, especially in cases of invasion of the skull base. In addition, long-term prognosis has not been reported in T4b cases. Herein, we report the case of a 36-year-old Japanese man with locally advanced nasal BSCC that directly invaded the skull base and the brain. The patient was then treated with induction chemotherapy (IC). Owing to his good response to IC, we planned and performed en bloc resection followed by adjuvant proton beam therapy (PBT). Follow-up examinations five years after treatment showed no evidence of recurrence. This is the first report of IC followed by radical surgery and adjuvant PBT in a patient with T4b. IC has the potential to play an important role in treatment strategies.

Epidemiology of post-suboccipital craniotomy headache: A multicentre retrospective study.

The detailed epidemiology and mechanism of post-craniotomy headaches are not well understood. This study aimed to establish the actual clinical incidence and causes of post-craniotomy headaches. Suboccipital craniotomy surgeries performed in six institutions within the five-year study period were included. This study included 311 patients (138 males, 173 female; mean age, 59.3 years old). A total of 145 patients (49%) experienced post-craniotomy headaches. Microvascular decompression surgery, craniectomy and facial spasms were significant risk factors for post-craniotomy headaches. In most cases, the post-craniotomy headaches disappeared within one month; however, some patients suffered from long-term headaches. The craniotomy site and the methods of dura and skull closures should be individually determined for each patient. However, to prevent post-craniotomy headaches, craniotomy, instead of craniectomy, may be considered.

Risk Factors for Postoperative Cerebrospinal Fluid Leak after Graded Multilayer Cranial Base Repair with Suturing via the Endoscopic Endonasal Approach.

This study analyzed risk factors for postoperative cerebrospinal fluid (CSF) leak after graded multilayer cranial base repair method with dural suturing. We performed surgery via the endoscopic endonasal approach (EEA) from 2012.6 to 2018.4, and those consecutive clinical data were prospectively accumulated and retrospectively analyzed. We tailored the repair method according to the intraoperative CSF leak grade. Among 388 surgeries via the EEA, there were 10 (2.6%) cases of postoperative CSF leak after graded repair with suturing. Postoperative CSF leak occurred in two of the 150 cases without intraoperative CSF leak (grade 0), one of the 104 cases with small (grade 1) intraoperative CSF leak, two of the 60 cases with moderate (grade 2) leak, and five of the 74 cases with large (grade 3) leak. Univariate analysis indicated that chordoma (P = 0.023), estimated tumor volume ≥ 7400 mm3 (P = 0.003), and maximum tumor diameter ≥ 32.5 mm (P = 0.001) were significant risk factors for postoperative CSF leak. Additionally, among cases with intraoperative grade 3 CSF leak, chordoma (P = 0.021), estimated tumor volume ≥ 23000 mm3 (P = 0.003), and maximum tumor diameter ≥ 45.5 mm (P = 0.001) were significant risk factors for postoperative CSF leak. Maximum tumor diameter, estimated tumor volume, and chordoma tumor pathology are related to a higher risk of postoperative CSF leak.

Intraosseous schwannoma in the clivus mimicking chordoma treated with endoscopic endonasal surgery: A case report.

Background: Intraosseous schwannomas are extremely rare and they have not yet been reported to occur in the clivus. We report a schwannoma in the clivus mimicking chordoma and review intraosseous schwannomas of the skull. Case Description: A 62-year-old man presented with gradually worsening hoarseness with dysphagia and atrophy of the left tongue, trapezius muscle, and sternocleidomastoid muscle. Magnetic resonance imaging showed that the tumor was mainly located in the clivus, and a computed tomography (CT) scan revealed an osteolytic lesion with expansion of the clivus and preservation of the bony cortex. Endoscopic endonasal surgery was performed to diagnose and treat symptoms. The tumor was subtotally removed without any complications. The histopathological findings revealed typical schwannoma, which showed Antoni A and Antoni B patterns positive for S100 protein. Based on the preoperative imaging, intraoperative and histopathological findings, the tumor was considered to be an intraosseous schwannoma in the clivus, and no recurrence was observed after 1 year of postoperative follow-up. Conclusion: Even though the intraosseous schwannoma in the clivus is uncommon, it should be considered as a differential diagnosis if an expansive lesion without destruction of the cortical bone is shown on CT as well as iso-hyperintensity on T2-weighted magnetic resonance imaging.

Factors Influencing Craniospinal Relapse of Intracranial Germinoma After Complete Remission.

OBJECTIVE: To evaluate the pathomechanism of the recurrence of intracranial germinoma after complete response and to confirm the association of the initial magnetic resonance imaging and therapeutic factors with recurrence. METHODS: This study included patients who were followed up for ≥5 years and who were treated in our hospital from 1980 to 2021. Those with germinoma and germinoma with syncytiotrophoblastic giant cells were diagnosed pathologically. Data were categorizedbased on "gender," "single region," "intraventricular dissemination at the initial diagnosis," "hydrocephalus," "types of radiation therapy (RT)," and "chemotherapy." Fisher's exact probability test was used to assess differences between the no recurrence and recurrence groups. RESULTS: Among 43 patients, 34 had no recurrence, 5 had delayed recurrence (≥60 months), and 4 had early recurrence (<60 months). Follow-up periods were 143.5 (60-380), 198 (88-222), and 132.5 (75-291) months for the no recurrence, delayed recurrence, and early recurrence groups, respectively. Five patients with delayed recurrence showed 3 intracranial lesions and 2 spinal lesions. Four patients with early recurrence showed 3 intracranial lesions and 1 spinal lesion. Differences in delayed recurrences (focal RT vs. RT including whole-ventricle system; P = 0.0491) were significant in Fisher's exact test. CONCLUSIONS: RT including the whole-ventricle system reduces delayed craniospinal relapses including dissemination, local, and distant recurrences even ≥5 years after complete response in patients with primary central nervous system germinoma.

Levetiracetam Versus Levetiracetam Plus Sodium Channel Blockers for Postoperative Epileptic Seizure Prevention in Brain Tumor Patients.

Background Brain tumor patients tend to develop postoperative epileptic seizures, which can lead to an unfavorable outcome. Although the incidence of postoperative epileptic seizures and adverse events are improved with the advent of levetiracetam (LEV), postoperative epilepsy occurs at a frequency of 4.6% or higher. In brain tumor patients, the addition of sodium channel blockers (SCBs) to LEV significantly reduces seizures, though confirmed in a non-postoperative study. Thus, the combination of SCBs with LEV might be promising. Objective In this prospective randomized controlled trial we investigated the safety, evaluated by adverse events during one and two weeks after surgery, and the efficacy, evaluated by the incidence of early epilepsy, including non-convulsive status epilepticus (NCSE), of using LEV alone or SCBs added to LEV in patients who underwent craniotomy or biopsy for brain tumors or brain mass lesions. Methods Patients with brain tumors or brain mass lesions undergoing surgical interventions, excluding endoscopic endonasal surgery (EES), with a diagnosis of epilepsy were eligible for this study. Patients are randomized into either Group A or B (B1 or B2) after the informed consents are taken; LEV alone in Group A patients, while LEV and SCBs in Group B patients (GroupB1, intravenous fosphenytoin plus oral lacosamide (LCM) and GroupB2, intravenous LCM plus oral LCM) were administered postoperatively. Fifty-three patients were enrolled during the first two and a half years of the study and four of them were excluded, resulting in the accumulation of 49 patients' data. Results Postoperative epileptic seizures occurred only in three out of 49 patients during the first week (6.1%) and in seven patients within two weeks after surgery (14.3%, including the three patients during the first week). In Group A, epileptic seizures occurred in two out of 26 patients during the first week (7.7%) and in five patients within two weeks (19.2%) after surgery. In Group B, epileptic seizures occurred in one out of 23 patients during the first week (4.3%) and in two patients during the first two weeks (8.7%). Low complication grade of epileptic seizures was observed in Group B rather than in Group A, however, without significant difference (p=0.256). There was no difference in the frequency of adverse effects in each group. Conclusion Although not statistically significant, the incidence of epileptic seizures within one week after surgery was lesser in LEV+SCBs groups than in LEV alone. No hepatic damage or renal function worsening occurred with the addition of LCM, suggesting the safety of LEV+SCBs therapy.

Endoscopic Endonasal Dural Reconstruction for a Cerebrospinal Fluid Leak in the Middle Cranial Fossa of a Patient with Gorham-stout Disease with Skull Base Defect.

We report the use of endoscopic endonasal surgery for dural reconstruction following a cerebrospinal fluid leak in a 33-year-old patient with recurrent meningitis since at age of 2 years. Magnetic resonance imaging showed osteolytic changes in the left temporal and sphenoid bones, including the left pterygoid plate, a few left temporal encephaloceles, and cerebrospinal fluid-like fluid in the expanded Meckel's cave and the parapharyngeal space. After endoscopic endonasal surgery, Gorham-Stout disease was diagnosed. No recurrence of cerebrospinal fluid leakage or meningitis has been observed. Thus, endoscopic endonasal surgery might improve clinical outcomes in patients with Gorham-Stout disease and skull base defects.

Perioperative Deep Vein Thrombosis and D-dimer Measurement in Patients with Brain Tumor.

We investigated the appropriate D-dimer cutoff value for each brain tumor type for acute or subacute deep vein thrombosis (DVT) following transcranial brain tumor surgery.In this single-center retrospective study, a cumulative total of 128 patients who underwent transcranial brain tumor surgery were enrolled and classified into the glioma group, the other intracranial malignant tumor group, and the intracranial benign tumor group. Venous ultrasonography was performed if the D-dimer plasma levels were positive (≥1 µg/mL) before surgery and on postoperative day (POD) 3 or 7.Of the 128 cases, DVT developed in 32 (25.0%). Among those, acute or subacute DVT was diagnosed in 22 cases on POD 3 and in 8 cases on POD 7. Compared with DVT-negative cases on POD 3, acute or subacute DVT-positive cases on POD 3 revealed a significant increase in the D-dimer level in all groups combined and in the benign tumor group but not in the glioma group. With regard to DVT on POD 3 in all groups, the receiver operating characteristic curve for the D-dimer level on POD 3 demonstrated a cutoff value of 3.3 µg/mL (sensitivity [0.636] and specificity [0.750]). However, if this cutoff value was used in practice, eight cases would be false-negative with a minimum D-dimer level of 1.5 µg/mL.The D-dimer cutoff value for acute or subacute DVT on POD 3 could be set to 3.3 µg/mL; however, the setting resulted in several false-negative cases. Practically, 1.5 µg/mL of the D-dimer cutoff value on POD 3 might be appropriate to avoid false-negative results.

Inducing substances for chondrogenic differentiation of dental pulp stem cells in the conditioned medium of a novel chordoma cell line.

We successfully established a chordoma cell line, designated TSK-CHO1, derived from the clival chordoma. Currently, there is only one skull base chordoma cell line, UM-chor1, freely available to researchers. The established TSK-CHO1 cells were neoplastic, exhibited pleomorphic features, and secreted brachyury, as revealed by immunocytochemical staining or ELISA of conditioned medium (CM). Cells also secreted SOX9, which enhanced brachyury production. The CM of TSK-CHO1 cells promoted the production of hyaluronic acid and type II collagen during differentiation of human dental pulp stem cells (DPSCs) into fibrocartilage cells. Culture of DPSC pellets in a growth medium supplemented with 10% CM of TSK-CHO1 cells for 2 weeks resulted in the induction of fibrocartilage tissue under normoxic conditions. Brachyury produced by TSK-CHO1 cells promoted the production of collagen type II, peculiar to cartilage, in a dose-dependent manner. The newly established skull base chordoma cell line, TSK-CHO1, is expected to be used for elucidating the pathogenesis of skull base chordoma and for investigating the mechanism underlying the production of fibrocartilage.

Endoscopic endonasal transmaxillary-pterygoid approach for skull-base non-vestibular schwannomas in 10 consecutive patients.

PURPOSE: Non-vestibular schwannomas (NVSs) of the skull base occur in several sites, and few previous studies have evaluated the usefulness of the endoscopic endonasal transmaxillary-pterygoid approach (EETMPA) to resect these lesions. We aimed to evaluate the characteristics and clinical outcomes of patients who underwent EETMPA for skull-base NVSs and to investigate the efficacy, safety, and indications for the procedure. METHODS: We retrospectively reviewed the clinical data of 10 consecutive patients (mean age, 45 ± 17) who underwent EETMPA for skull-base NVSs at the University of Tsukuba hospital between 2013 and 2020. We also calculated the total tumor volume and the size of the corridor to the tumor for EEA (SCEEA) in nine patients who underwent EEA for NVSs adjacent to the Meckel's cave or cavernous sinus. RESULTS: Nine patients (9/10), including five women (5/10), underwent primary surgery. Gross total resection and subtotal resection were achieved in five patients each (5/10). Postoperatively, one patient showed a new and mild cranial nerve V sensory deficit and one patient showed slight worsening of abducens nerve palsy. The greater palatine nerve was amputated in two patients; however, permanent perception loss in the soft palate was observed in one patient. The Vidian nerve was sacrificed in four patients, and new dry eye occurred in one patient. None of the patients experienced postoperative tumor recurrence or regrowth during the follow-up period of 40 ± 28 months. CONCLUSION: EETMPA is safe and effective for excising skull-base NVSs which are not eligible for radiosurgery leading to a high rate of successful resection and a high rate of but mild neurological sequela. The EEA is appropriate when the tumor extends to the paranasal sinus with sufficient SCEEA.

Objective evaluation of gustatory function after surgery for vestibular schwannoma: A pilot study.

OBJECTIVE: To evaluate the gustatory function before and after vestibular schwannoma (VS) surgery. METHODS: In this retrospective study, we evaluated the gustatory function of 12 patients who underwent VS surgery at Tsukuba University Hospital between 2012 and 2018. Gustatory function was examined using electrogustometry before VS surgery and 3 months, 6 months and 1 year after surgery. Electrogustometry was tested at the area mapped to the chorda tympani nerve, glossopharyngeal nerve and greater superficial petrosal nerve (GSPN). Intergroup mean comparisons of the threshold were performed using a one-way analysis of variance (ANOVA) followed by the Bonferroni post-hoc test. RESULTS: The gustatory function mapped to the chorda tympani nerve was significantly disturbed 6 months after the surgery as compared with the preoperative function (p = 0.033) and that the dysfunction recovered at 1 year. However, gustatory function mapped to the glossopharyngeal nerve and greater superficial petrosal nerve (GSPN) was not impaired. CONCLUSION: The gustatory function mapped to the chorda tympani nerve is impaired after surgery for VS. The dysfunction peaked at 6 months after surgery, and recovered within 1 year.

Involvement of the optic pathway and outcome of visual function in patients with neurohypophyseal germ cell tumor.

BACKGROUND: Patients with neurohypophyseal germ cell tumors (GCTs) typically present with visual problems. Hence, this study aimed to assess optic pathway involvement based on clinical and radiological findings and to validate the outcome of visual function. METHODS: A total of 16 patients with newly diagnosed neurohypophyseal GCTs who were treated at the University of Tsukuba Hospital between 2000 and 2020 were included in this study. RESULTS: The median interval from symptom onset to diagnosis was 173.5 days (range, 33-1588 days). Patients with visual disturbance at diagnosis had a longer time to diagnosis compared with those without. Ophthalmologic abnormalities were frequently observed, with an incidence rate of 69%. Fifty percent of patients exhibited optic pathway involvement detected via magnetic resonance imaging (MRI). Visual impairment was more severe in the patients with optic pathway involvement (p = 0.002). Post-treatment visual impairment was improved but was still significantly severe in patients with optic pathway involvement than in those without involvement (p = 0.010). Visual field deficit more likely remained with an improvement rate of 50%, whereas the improvement rate of visual acuity was 78%. Further, none developed late-onset visual deterioration during the follow-up period. CONCLUSIONS: Visual disturbance and optic pathway involvement are common in neurohypophyseal GCTs. Visual impairment particularly in patients with optic pathway involvement on MRI is more likely to remain at follow-up, although the outcome of visual function is acceptable in most cases.