[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.

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.

[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.

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.

Maximum resection and immunotherapy improve glioblastoma patient survival: a retrospective single-institution prognostic analysis.

Glioblastoma (GBM) is a refractory disease with a poor prognosis and various methods, including maximum resection and immunotherapy, have been tested to improve outcomes. In this retrospective study we analyzed the prognostic factors of 277 newly diagnosed GBM patients over 11 years of consecutive cases at our institution to evaluate the effect of these methods on prognosis. Various data, including the extent of removal (EOR) and type of adjuvant therapy, were examined and prognostic relationships were analyzed. The median overall survival (OS) of the entire 277-case cohort, 200 non-biopsy cases, and 77 biopsy cases was 16.6 months, 19.7 months, and 9.7 months, respectively. Gross total removal (GTR; 100% of EOR) was achieved in 32.9% of the cases. Univariate analysis revealed younger age, right side, higher Karnofsky performance status, GTR, intraoperative magnetic resonance imaging (MRI) use for removal, proton therapy, combination immunotherapy, and discharge to home as good prognostic factors. Intraoperative MRI use and EOR were closely related. In the multivariate analysis, GTR, proton therapy, and a combination of immunotherapies, including autologous formalin-fixed tumor vaccine, were the significant prognostic factors. A multivariate analysis of 91 GTR cases showed that immunotherapy contributed to prognostic improvements. The median OS and 5-year OS % values were 36.9 months and 43.3% in GTR cases receiving immunotherapy. In conclusion, GTR, proton therapy, and immunotherapy were good prognostic factors in single-center GBM cases. Tumor vaccine therapy for GTR cases achieved a notably high median survival time and long-term survival ratio, indicating its usefulness in GTR cases.

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.

Long-term results of cabergoline therapy for macroprolactinomas and analyses of factors associated with remission after withdrawal.

OBJECTIVE: Withdrawal of cabergoline is generally challenging, especially in patients with large or invasive macroprolactinomas. Therefore, we aimed to assess long-term results of cabergoline therapy for macroprolactinomas and remission achievement results after withdrawal in patients with macroprolactinomas. We also investigated clinical characteristics and factors related to remission after withdrawal. METHODS: This was an institutional review board-approved retrospective analysis. We studied 46 macroprolactinoma patients who had taken cabergoline during the period from 2003 through 2013. Administration of cabergoline was maintained for 5 years before withdrawal. RESULTS: Median follow-up after the initiation of cabergoline therapy was 54·3 (range 5·3 to 137·2) months. Recurrences of hyperprolactinaemia were observed in 3 of 11 (27%) postwithdrawal patients at a median time of 3·0 (range; 2·9-11·2) months, indicating that a high percentage (73%) maintained remission for at least 12 months after cabergoline cessation. Factors significantly associated with remission were analysed in 21 patients receiving long-term cabergoline administration. On multivariate analysis, the absence of cavernous sinus invasion on pretreatment MRI (≥3/4 tumour encasement of the intracavernous internal carotid artery) (HR; 21·94, 95% CI; 2·06-1071·0, P = 0·006), initial PRL <132·7 ng/ml (HR; 8·28, 95% CI; 1·24-199·6, P = 0·03) and nadir PRL <1·9 ng/ml during cabergoline therapy (HR; 5·14, 95% CI; 1·10-39·02, P = 0·04) showed statistically significant correlations with remission after withdrawal. CONCLUSIONS: Cabergoline therapy can achieve a high percentage (73% in this series) of remission maintenance for at least 12 months after cessation of a 5-year course of therapy, even in patients with macroprolactinomas. The absence of cavernous sinus invasion, serum PRL level lower than 132·7 ng/ml before cabergoline therapy or nadir serum PRL below 1·9 ng/ml were related to more frequent remission after withdrawal of cabergoline in patients receiving this medication for 5 years.

Assessment of PD-1 positive cells on initial and secondary resected tumor specimens of newly diagnosed glioblastoma and its implications on patient outcome.

Glioblastoma (GBM) is the most common type of malignant brain tumor and has a very poor prognosis. Most patients relapse within 12 months despite aggressive treatment and patient outcome after recurrent is extremely worse. This study was designed to clarify the change of the molecular expression, including programmed cell death 1 (PD-1) and PD-ligand 1 (PD-L1), on the initial and secondary resected tumor specimens and to address the influence of these expressions for patient outcome after second surgery of glioblastoma. We investigated 16 patients, ranging in age from 14 to 65 years, with histologically verified WHO grade IV GBM, whose original tumor was resected between 2008 and 2014, and treated with fractionated radiotherapy and temozolomide. Four patients who were treated with immunotherapy using autologous formalin-fixed tumor vaccine were enrolled. All of the patients underwent secondary resection after tumor recurrence within 24 months. We carried out an immunohistochemical examination of the initial and secondary resected tumors from patients using a panel of immune system molecular markers, and assessed whether marker expression correlated with clinical outcomes. CD3, CD8 and PD-1 on tumor-infiltrating lymphocytes was significantly increased in secondary resected specimens compared with initially resected specimens (p ≤ 0.05). All patients expressed PD-L1 on tumor cells in initial and secondary resection specimens. Patients were divided into high or low expression group by median IHC score of PD-1 on initial or secondary resected specimens. No significant differences in patient outcomes were observed between high and low PD-1 or PD-L1 groups of initially resected specimens. In high expression group of secondary resected specimens, most patients score had increased which compared with initial resected tumor specimens. The PD-1 high expression score group of secondary resected specimens was associated with long progression-free survival and short survival after recurrence. PD-L1 expression was detected in almost all initial and secondary specimens. Patients with high PD-1 expression of secondary specimen had bad prognosis after secondary resection. PD-1/PD-L1 pathway may be associated with patient outcome after second surgery of glioblastoma.

[Endoscopic Endonasal Transethmoidal Biopsy for IgG4-Related Intraorbital Pseudotumor:A Case Report].

BACKGROUND: We experienced a case of intraorbital pseudotumor associated with IgG4-related disease, for which we successfully performed an endoscopic endonasal transethmoidal biopsy for the intraorbital pseudotumor as well as endoscopic sinus surgery for a refractory pansinusitis at the same time. CASE REPORT: A 59-year-old man was referred to our hospital because of an intraorbital mass lesion. MRI showed 2 mass lesions:a large intraconal lesion encasing the left optic nerve on the orbital apex, and a small extraconal lesion medial to the left medial rectus muscle extending into the anterior ethmoid canal. In addition, CT showed severe pansinusitis. A blood test showed a marked elevation of IgG4. IgG4-related pseudotumor was suspected, but IgG4-related MALT lymphoma was an alternative diagnosis, and a biopsy of the mass lesion was required. We successfully performed both, an endoscopic endonasal transethmoidal biopsy for the mass lesion and endoscopic sinus surgery for the refractory pansinusitis at the same time. The pathological diagnosis was an IgG4-related pseudotumor. CONCLUSION: Endoscopic endonasal transethmoidal biopsy is an effective and minimally invasive method for making a definitive diagnosis of IgG4-related intraorbital pseudotumor. Using this method, refractory pansinusitis frequently associated with this disease can be treated. For successful treatment, interdisciplinary decision making and collaborative team surgery are crucial.

Abducent nerve palsy treated by microvascular decompression: a case report and review of the literature.

Too few cases of isolated abducent nerve palsy caused by neurovascular compression syndrome have been reported. We here report on a case of abducent nerve palsy caused by neurovascular compression syndrome that was successfully treated by microvascular decompression (MVD). A 46-year-old male presented with a 6-month history of right-sided persistent abducent nerve palsy. High-resolution magnetic resonance imaging revealed a neurovascular contact of the vertebral artery with the right abducent nerve. MVD was performed via a retrosigmoid craniotomy, with remarkable improvement of the palsy. Our report suggests that MVD might be considered as an optional treatment if the symptoms progress or persist.

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.

Decrease in the apparent diffusion coefficient in peritumoral edema for the assessment of recurrent glioblastoma treated by bevacizumab.

PURPOSES: Anti-edema effect of bevacizumab was evaluated using the apparent diffusion coefficient (ADC) of peritumoral edema associated with regional cerebral blood flow (rCBV) of the tumor. MATERIALS AND METHODS: Nine patients with recurrent glioblastoma were treated using bevacizumab for 4 ∼ 36 months (average 12 months). MRI was performed every 2 months. For each MRI, ADC value, Gd-enhanced area on T1 imaging, area of peritumoral edema on T2 imaging, and rCBV on perfusion imaging were measured. ADC and rCBV values were determined by the use of regions of interest positioned in areas of high signal intensity, as seen on T2-weighted images and ADC maps. RESULTS: After 2 months of bevacizumab treatment, ADC values and rCBV decreased 49 and 32 % respectively, associated with marked diminishment of the Gd-enhanced area compared with pretreatment. After 6 months, in 5 of the 9 cases, the Gd-enhanced area appeared again with no change in the ADC value and rCBV. In the other four cases, the Gd-enhanced area as well as the ADC value and rCBV returned to the initial status. CONCLUSION: The anti-edema effect of bevacizumab for treatment of recurrent glioblastoma that was demonstrated by decreased ADC values and rCBV was dramatic and -prolonged at 6 months even with tumor progression.

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.

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.

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.

[Granular cell tumor of the neurohypophysis observed with hypoglycemic attack].

Granular cell tumor of the neurohypophysis (GCT) occurs as a solitary, small, nodular tumor and rarely grows to a sufficient size to present symptoms. The authors report a case of a 30-year-old man with GCT presenting with hypoglycemic attack. Hypoglycemic attack could be due to dysfunction of the hypothalamus and one of the important symptoms of GCT.

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.