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Shunya Hanakita, Tomoyuki Koga, Masahiro Shin, Hiroshi Igaki and Nobuhito Saito

OBJECT

Although stereotactic radiosurgery (SRS) has been accepted as a therapeutic option for arteriovenous malformations (AVMs) in children and adolescents, substantial data are still lacking regarding the outcomes of SRS for AVMs in this age group, especially long-term complications. This study aimed to clarify the long-term outcomes of SRS for the treatment of AVM in pediatric patients aged ≤ 18 years.

METHODS

Outcomes of 116 patients who were aged 4–18 years when they underwent SRS between 1990 and 2009 at the study institute were analyzed retrospectively.

RESULTS

The median follow-up period after SRS was 100 months, with 6 patients followed up for more than 20 years. Actuarial obliteration rates at 3 and 5 years after SRS were 68% and 88%, respectively. Five hemorrhages occurred in 851 patient-years of follow-up. The annual bleeding rate after SRS before obliteration was calculated as 1.3%, which decreased to 0.2% after obliteration. Shorter maximum nidus diameter (p = 0.02) and higher margin dose (p = 0.03) were associated with a higher obliteration rate. Ten patients experienced adverse events after SRS. Of them, 4 patients presented with delayed complications years after SRS (range 9–20 years after SRS).

CONCLUSIONS

SRS can reduce the risk of hemorrhage in pediatric and adolescent AVMs, with an acceptable risk of complications in the long term. However, adverse events such as expanding hematoma and radiation necrosis that can occur after substantial follow-up should be taken into account at the time that treatment decisions are made and informed consent is obtained.

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Keisuke Maruyama, Masahiro Shin, Masao Tago, Hiroki Kurita, Nobutaka Kawahara, Akio Morita and Nobuhito Saito

Object

Appropriate management of hemorrhage after Gamma Knife surgery (GKS) for arteriovenous malformations (AVMs) of the brain is poorly understood, although a certain proportion of patients suffer from hemorrhage.

Methods

Among 500 patients observed for 1 to 183 months (median 70 months) after GKS, 32 patients (6.4%) suffered a hemorrhage. Hemorrhage developed even after angiographically documented obliteration of the AVM in five (2%) of 250 patients followed for 1 to 133 months (median 75 months) post-GKS. These patients had been treated according to their pathological condition. Treatment of these patients and their outcomes were retrospectively reviewed. As a management strategy in patients with preobliteration hemorrhage, the intracerebral hematoma and the AVM nidus were removed in four patients, and chronic encapsulated hematoma was removed in three. Among 11 patients who were conservatively treated, AVMs were ultimately obliterated in five, including three patients who underwent repeated GKS. Intracerebral hematoma from angiographically documented obliterated AVMs was radically resected in two patients, including one who also underwent aspiration of an accompanying symptomatic cyst. Intraoperative bleeding was easily controlled in these patients. Outcomes after hemorrhage, measured with the modified Rankin Scale, were significantly better in patients with postobliteration hemorrhage than in those with preobliteration hemorrhage (p < 0.05).

Conclusions

Various types of hemorrhagic complications after GKS for AVMs can be properly managed based on an understanding of each pathological condition. Although a small risk of bleeding remains after angiographically demonstrated obliteration, surgery for such AVMs is safe, and the patient outcomes are more favorable. Radical resection to prevent further hemorrhage is recommended for ruptured AVMs after obliteration because such AVMs can cause repeated hemorrhages.

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Keisuke Maruyama, Tomoyuki Koga, Masahiro Shin, Hiroshi Igaki, Masao Tago and Nobuhito Saito

Object

Optimal timing of Gamma Knife surgery (GKS) after hemorrhage from brain arteriovenous malformations (AVMs) is unclear and of concern to neurosurgeons because GKS is usually performed after absorption of the hematoma. The authors investigated whether waiting for hematoma absorption is beneficial and aimed to clarify the optimal treatment timing.

Methods

The authors retrospectively studied 211 patients with AVMs who presented with hemorrhage and underwent GKS as the initial treatment. Patients were categorized into 3 groups according to the interval between the time of first hemorrhage and GKS, as follows: Group 1, 0–3 months (70 patients); Group 2, 3–6 months (62 patients); and Group 3, > 6 months (79 patients). The obliteration rates, number of hemorrhages before and after GKS, and complication rates were compared between these 3 groups. The authors also analyzed a subgroup of 127 patients who presented with intracerebral hemorrhage (ICH) to identify the influence of ICH on outcome.

Results

After a median follow-up of 6.3 years, the rates of obliteration, hemorrhage after treatment, and complication were not significantly different between the 3 groups even though the patients with a longer interval before GKS (Group 3) had more AVMs in eloquent areas and neurological deficits. However, the numbers of patients with preoperative hemorrhage in the interval before GKS was significantly higher in Group 3 (1, 3, and 20 patients in Group 1, 2, and 3, respectively). These results were similar in the analyses of 127 patients presenting with ICH.

Conclusions

No benefit was detected in waiting for hematoma absorption until GKS after hemorrhage from AVM. Because of higher hemorrhagic risk until GKS > 6 months after hemorrhage, the authors recommend GKS within 6 months after hemorrhage.

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Hirokazu Takami, Masahiro Shin, Masafumi Kuroiwa, Ayako Isoo, Kan Takahashi and Nobuhito Saito

Cystic malformations in the posterior cranial fossa result from developmental failure in the paleocerebellum and meninges. The authors present the case of an infant with hydrocephalus associated with cystic dilation of the foramina of Magendie and Luschka.

This 7-month-old female infant presented with sudden onset of tonic-clonic seizures. Computed tomography revealed tetraventricular hydrocephalus. Magnetic resonance imaging demonstrated a cyst communicating with the fourth ventricle and projecting to the cisterna magna and the cerebellopontine cisterns through the foramina of Magendie and Luschka. A suboccipital craniotomy was performed for removal of the cyst wall, and the transparent membrane covering the foramen of Magendie was removed under a microscope. After the surgery, the patient's hydrocephalus improved and a phase contrast cine MR imaging study showed evidence of normal CSF flow at the level of the third and fourth ventricles. Three weeks later, however, the hydrocephalus recurred. An endoscopic third ventriculocisternostomy was performed to address the possibility of stagnant CSF flow in the posterior cranial fossa, but the hydrocephalus continued. Finally the patient underwent placement of a ventriculoperitoneal shunt, resulting in improvement of her symptoms and resolution of the hydrocephalus.

On the basis of this experience and previously published reports, the authors speculate that the cystic malformation in their patient could be classified in a continuum of persistent Blake pouch cysts. Hydrocephalus was caused by a combination of obstruction of CSF flow at the outlets of the fourth ventricle and disequilibrium between CSF production and absorption capacity.

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Hirotaka Hasegawa, Masahiro Shin, Kenji Kondo, Shunya Hanakita, Akitake Mukasa, Taichi Kin and Nobuhito Saito

OBJECTIVE

Skull base chondrosarcoma is one of the most intractable tumors because of its aggressive biological behavior and involvement of the internal carotid artery and cranial nerves (CNs). One of the most accepted treatment strategies for skull base chondrosarcoma has been surgical removal of the tumor in conjunction with proactive extensive radiation therapy (RT) to the original tumor bed. However, the optimal strategy has not been determined. The goal of this study was to evaluate the early results of endoscopic transnasal surgery (ETS).

METHODS

The authors retrospectively analyzed 19 consecutive patients who underwent ETS at their institution since 2010. Adjuvant stereotactic radiosurgery (SRS) was performed only for the small residual tumors that were not resected to avoid critical neurological complications. Histological confirmation and evaluation of the MIB-1 index was performed in all cases. The Kaplan-Meier method was used to determine the actuarial rate of tumor-free survival.

RESULTS

The median tumor volume and maximal diameter were 14.5 cm3 (range 1.4–88.4 cm3) and 3.8 cm (range 1.5–6.7 cm), respectively. Nine patients (47%) had intradural extension of the tumor. Gross-total resection was achieved in 15 (78.9%) of the 19 patients, without any disabling complications. In 4 patients, the surgery resulted in subtotal (n = 2, 11%) or partial (n = 2, 11%) resection because the tumors involved critical structures, including the basilar artery or the lower CNs. These 4 patients were additionally treated with SRS. The median follow-up duration was 47, 28, and 27 months after the diagnosis, ETS, and SRS, respectively. In 1 patient with an anterior skull base chondrosarcoma, the tumor relapsed in the optic canal 1 year later and was treated with a second ETS. Favorable tumor control was achieved in all other patients. The actuarial tumor control rate was 93% at 5 years. At the final follow-up, all patients were alive and able to perform independent activities of daily living without continuous neurological sequelae.

CONCLUSIONS

These preliminary results suggest that ETS can achieve sufficient radical tumor removal, resulting in comparative resection rates with fewer neurological complications to those in previous reports. Although the follow-up periods of these cases were relatively short, elective SRS to the small tumor remnant may be rational, achieving successful tumor control in some cases, instead of using proactive extensive RT. Thus, the addition of RT should be discussed with each patient, after due consideration of histological grading and biological behavior. To determine the efficacy of this strategy, a larger case series with a longer follow-up period is essential. However, this strategy may be able to establish evidence in the management of skull base chondrosarcoma, providing less-invasive and effective options as an initial step of treatment.

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Shunya Hanakita, Tomoyuki Koga, Masahiro Shin, Masaaki Shojima, Hiroshi Igaki and Nobuhito Saito

Object

The goal of this study was to assess the efficacy of Gamma Knife surgery (GKS) in the management of dural arteriovenous fistulas (dAVFs).

Methods

The authors performed a retrospective analysis of a group of 22 patients who underwent GKS for dAVFs at the University of Tokyo Hospital between 1991 and 2009. The patients underwent CT or MR imaging with contrast enhancement every 6 months after GKS; when obliteration of a dAVF was indicated by these images, patients also underwent angiography. Follow-up in these patients ranged from 12 months to 100 months (median 33 months) after GKS.

Results

Obliteration of the dAVF was confirmed by neuroimaging in 12 patients (55%). According to a Kaplan-Meier analysis, obliteration rates for the dAVFs were 51% at 3 years and 80% at 5 years. The obliteration rate for lesions without cortical venous drainage (CVD) was 86%, which was significantly higher than the rate for dAVFs with CVD (47%) (p = 0.007). Hemorrhage at presentation (p = 0.03), a target volume less than 1.5 cm3 (p = 0.009), and Cognard Type III or IV dAVF (p = 0.005) were factors associated with a higher obliteration rate. Among 10 patients whose dAVFs were not obliterated by the initial GKS, 5 patients underwent additional treatment and complete obliteration was achieved in all. Relief of tinnitus was obtained in 5 (83%) of 6 patients with transverse-sigmoid sinus dAVFs, and ophthalmic symptoms improved in 2 (67%) of 3 patients with cavernous sinus dAVFs. No patient experienced interval hemorrhage or radiation-induced complications after treatment.

Conclusions

Gamma Knife surgery is a safe and effective treatment for dAVF. It can be a first line of therapy in the multidisciplinary treatment strategy for dAVFs, especially when significant morbidity is anticipated with other therapeutic options. One should be very careful about recommending GKS for patients harboring dAVFs with CVD because of the expected natural history of such a lesion and the possibility of other therapeutic options.

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Shunya Hanakita, Tomoyuki Koga, Hiroshi Igaki, Naoya Murakami, Soichi Oya, Masahiro Shin and Nobuhito Saito

Object

Atypical meningioma often recurs even after resection. As a salvage modality, radiotherapy or stereotactic radiosurgery (SRS) is attempted for this aggressive tumor. This retrospective study was performed to evaluate the efficacy of SRS that involved Gamma Knife surgery (GKS) for atypical meningioma.

Methods

The authors reviewed records from 22 patients with histologically proven atypical meningioma who underwent GKS for 28 lesions at the authors' institute. The median patient age was 70 years (range 24–91 years), and the median tumor volume for each procedure was 6.0 cm3 (range 1.6–38.7 cm3). The margin dose ranged from 14 to 20 Gy (median 18 Gy). Follow-up periods ranged from 3 months to 98 months (median 23.5 months).

Results

In total, 39 GKS procedures were performed for 28 lesions. The local control rates at 1, 2, and 5 years were 74%, 39%, and 16%, respectively. Volume less than 6 cm3 (p = 0.01), a margin dose higher than 18 Gy (p = 0.02), and a Karnofsky Performance Scale (KPS) score of 90 or more (p = 0.02) were factors associated with a longer duration of tumor control in the univariate analysis.

Conclusions

Atypical meningioma could be more successfully controlled when a higher margin dose was used to treat patients with a good performance (KPS score of ≥ 90) status and smaller tumor volumes. It would be desired if patients are treated with a relatively higher margin dose, ideally as high as the dose applied for malignant tumor. A boost SRS after fractionated radiotherapy may be effective to achieve better local control.

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Kenichi Usami, Kensuke Kawai, Tomoyuki Koga, Masahiro Shin, Hiroki Kurita, Ichiro Suzuki and Nobuhito Saito

Object

Despite the controversy over the clinical significance of Gamma Knife surgery (GKS) for refractory mesial temporal lobe epilepsy (MTLE), the modality has attracted attention because it is less invasive than resection. The authors report long-term outcomes for 7 patients, focusing in particular on the long-term complications.

Methods

Between 1996 and 1999, 7 patients with MTLE underwent GKS. The 50% marginal dose covering the medial temporal structures was 18 Gy in 2 patients and 25 Gy in the remaining 5 patients.

Results

High-dose treatment abolished the seizures in 2 patients and significantly reduced them in 2 others. One patient in this group was lost to follow-up. However, 2 patients presented with symptomatic radiation necrosis (SRN) necessitating resection after 5 and 10 years. One patient who did not need necrotomy continued to show radiation necrosis on MRI after 10 years. One patient died of drowning while swimming in the sea 1 year after GKS, before seizures had disappeared completely.

Conclusions

High-dose treatment resulted in sufficient seizure control but carried a significant risk of SRN after several years. Excessive target volume was considered as a reason for delayed necrosis. Drawbacks such as a delay in seizure control and the risk of SRN should be considered when the clinical significance of this treatment is evaluated.

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Ryohei Otani, Akitake Mukasa, Masahiro Shin, Mayu Omata, Shunsaku Takayanagi, Shota Tanaka, Keisuke Ueki and Nobuhito Saito

OBJECTIVE

Chordoma is a slow-growing but clinically malignant tumor, and the prognosis remains poor in many cases. There is a strong impetus to develop more effective targeted molecular therapies. On this basis, the authors investigated the potential of Brachyury, a transcription factor involved in notochord development, as a candidate molecular target for the treatment of chordoma.

METHODS

Brachyury gene copy number and expression levels were evaluated by quantitative polymerase chain reaction in 27 chordoma samples, and the transcriptomes of Brachyury high-expression tumors (n = 4) and Brachyury low-expression tumors (n = 4) were analyzed. A chordoma cell line (U-CH2) was used to investigate the signaling pathways that regulate Brachyury expression.

RESULTS

All chordoma specimens expressed Brachyury, and expression levels varied widely. Patients with higher Brachyury expression had significantly shorter progression-free survival (5 months, n = 11) than those with lower expression (13 months, n = 16) (p = 0.03). Somatic copy number gain was confirmed in 12 of 27 (44%) cases, and copy number was positively correlated with Brachyury expression (R = 0.61, p < 0.001). Expression of PI3K/Akt pathway genes was upregulated in Brachyury high-expression tumors, and suppression of PI3K signaling led to reduced Brachyury expression and inhibition of cell growth in the U-CH2 chordoma cell line.

CONCLUSIONS

Activation of the PI3K/Akt pathway and Brachyury copy number gain are strongly associated with Brachyury overexpression, which appears to be a key event in chordoma growth regulation. These findings suggest that targeting Brachyury and PI3K/Akt signaling may be an effective new approach for treating chordoma.

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Masahiro Shin, Kenji Kondo, Shunya Hanakita, Keigo Suzukawa, Taichi Kin, Masaaki Shojima, Daichi Nakagawa and Nobuhito Saito

OBJECT

In recent years, application of endoscopic transnasal surgery (ETS) has been expanded to orbital lesions, and preliminary results have started to be published for medially located soft mass lesions. However, reports on experience with endoscopic intraorbital surgery aimed at resection of invasive skull base tumors remains quite limited. This report presents the authors’ experience with ETS for locally aggressive tumors involving the orbit.

METHODS

ETS was performed for 15 cases of aggressive tumors involving the orbit: 5 meningiomas (meningothelial, n = 3; atypical, n = 1; anaplastic, n = 1), 4 chordomas, 2 chondrosarcomas, and 4 others (metastasis from systemic myxofibrosarcoma, schwannoma, inverted papilloma, and acinic cell carcinoma, n = 1 each). Among these, 9 tumors were located outside the periorbita and 6 inside the periorbita. In 6 intraperiosteal tumors, 5 were intraconal lesions, of which 3 arose in the muscle cone (anaplastic meningioma, optic sheath meningioma, and metastatic myxofibrosarcoma), and 2 meningothelial meningioma had invaded from the sphenoid ridge or the cavernous sinus into the muscle cone through the optic canal and the superior orbital fissure. A case of schwannoma originated around the cavernous sinus and pterygopalatine fossa and extended extraconally into the periorbita. Intraoperatively, ethmoid air cells and the lamina papyracea were removed, and extraperiosteal tumors were safely approached. For intraperiosteal tumors, the periorbita was widely opened, and the tumors were approached through the surgical window between the rectus and oblique muscles.

RESULTS

Gross-total resection was achieved for 12 of the 15 tumors, including 2 intraconal lesions. After surgery, exophthalmos resolved in all 8 patients with this symptom, and diplopia resolved in 5 of 6 patients. Improvement of visual symptoms was reported by 4 of 5 patients with loss of visual acuity or constriction of the visual field. Postoperatively, 1 patient showed mild, transient worsening of existing facial dysesthesia, and another showed transient ptosis and mild hypesthesia of the forehead on the affected side. All those symptoms resolved within 3 months. No patients showed enophthalmos, worsening of diplopia or visual function, or impairment of olfaction after surgery.

CONCLUSIONS

ETS appears acceptable as a less-invasive alternative for treating aggressive tumors involving the orbit. For extraperiosteal tumors, gross-total removal can generally be achieved without neurological complications. For intraperiosteal tumors, surgical indications should be carefully discussed, considering the relationship between the tumor and normal anatomy. Wide opening of the periorbital window is advocated to create a sufficient surgical pathway between the extraocular muscles, allowing a balance between functional preservation and successful tumor resection.