Shunya Hanakita

The long-term outcomes of radiosurgery for arteriovenous malformations in pediatric and adolescent populations

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.

The long-term outcomes of radiosurgery for intracranial hemangioblastomas

BACKGROUND Optimal timing in the treatment of intracranial hemangioblastoma (HB) remains controversial, particularly for patients of von Hippel-Lindau disease (VHL) with multiple small lesions. We evaluated efficacy of stereotactic radiosurgery (SRS) for intracranial HB based on the longer follow-up data with a larger number of patients and lesions. METHODS Twenty-one patients (11 men, 10 women) initially underwent SRS for 57 intracranial HBs. Seven patients had sporadic lesions and 14 had VHL-related lesions. During the follow-up, 40 lesions were additionally treated in VHL patients in 10 SRS treatments. Thus, a total of 97 lesions were included in this study. Median tumor volume was 0.13 cm(3) (range, 0.004-9.5 cm(3)), and median margin dose was 18 Gy (range, 14-20 Gy). RESULTS Median duration of follow-up was 96 months (range, 3-235 mo) after initial SRS treatment. Ten tumors in 7 patients showed progression after SRS. Actuarial tumor control rates after SRS at 5 and 10 years were 94% and 80%, respectively. Factors associated with longer control were solid lesion (P = .03), smaller volume (P = .01), and lesions associated with VHL (P = .0005) in univariate analysis. Five- and 10-year tumor control rates were 67% and 44% for sporadic patients and 97% and 83% for VHL patients. CONCLUSION SRS could be offered as an effective treatment for small, solid, and VHL-associated HBs. If the tumors show apparent enlargement in size or can possibly become symptomatic along with a slight increase in size, SRS should be recommended before they present with the clinical symptoms.

Role of Gamma Knife surgery in the treatment of intracranial dural arteriovenous fistulas

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 cm(3) (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.

Outcomes of Volume-Staged Radiosurgery for Cerebral Arteriovenous Malformations Larger Than 20 cm3 with More Than 3 Years of Follow-Up

OBJECTIVE Treatment of extremely large cerebral arteriovenous malformations (AVMs) is challenging. Although volume-staged stereotactic radiosurgery (SRS) is a possible multimodal treatment option for such lesions, reports of these procedures are scarce. We evaluated the efficacy and safety of volume-staged SRS in patients with AVMs >20 cm(3) with >3 years of follow-up. METHODS Between 2005 and 2012, 18 patients with AVMs >20 cm(3) were treated by volume-staged SRS. The median target volume was 38 cm(3) (interquartile range, 31-53 cm(3)). Treatment was conducted in 2-3 stages with a median interval of 6 months. RESULTS The median follow-up period from the last SRS treatment was 53 months (interquartile range, 41-75 months). Complete nidus obliteration was achieved in 6 patients (33%), and the obliteration rate at 5 years after initial SRS was 35% by the Kaplan-Meier method. The annual hemorrhage rate after last SRS treatment was 3.9% (95% confidence interval, 0.8%-11.5%). Radiation-induced adverse effects occurred in 2 patients. CONCLUSIONS In our series, volume-staged SRS for AVMs >20 cm(3) achieved a nidus obliteration rate of 35% at 5 years. There was still a high risk for hemorrhage (∼ 4% per year) after treatment, which seemed to be higher than the rate commonly observed in the posttreatment course of single-session SRS for average-size AVMs. Further cases will help determine whether volume-staged SRS could be routinely considered, based on its efficacy and risks, including comparison with the natural history of large AVMs.

Application of single-stage stereotactic radiosurgery for cerebral arteriovenous malformations >10 cm3.

Background and Purpose— Stereotactic radiosurgery (SRS) is a safe and effective treatment for small arteriovenous malformations (AVMs), the use of this modality for the treatment of large AVMs is still controversial, although it has been used in difficult cases. The aim of this study was to evaluate the treatment outcomes of patients who underwent single-stage SRS for large AVMs and to discuss the role of SRS in the treatment of these challenging lesions. Methods— Between 1998 and 2010, 65 patients with AVMs >10 cm3 underwent single-stage SRS using the Leksell Gamma Knife. Patients who had prospective volume-staged SRS were excluded from this series. Outcomes including the rates of obliteration, hemorrhage after treatment, and adverse events were retrospectively evaluated. Results— The mean nidus volume was 14.9 cm3 (±3.8 cm3), and a mean margin dose of 20 Gy (±1.5 Gy) was applied. The mean observation period was 60 months (range, 7–178 months). The nidus obliteration rates after SRS were 44%, 76%, and 81% at 3, 5, and 6 years, respectively. The annual hemorrhage rate after SRS was 1.94% and permanent adverse events were observed in 2 patients (3%). Conclusions— For large AVMs <20 cm3, single-stage radiosurgery by applying >16 Gy marginal dose presented favorable obliteration rates with relatively low rate of morbidity. Further accumulation of cases is awaited to fully evaluate the results of single-stage radiosurgery for large AVMs.

The Safety and Effectiveness of Low-Dose Recombinant Tissue Plasminogen Activator (0.6 mg/kg) Therapy for Elderly Acute Ischemic Stroke Patients (≥ 80 Years Old) in the Pre-endovascular Era

There are still few studies of low-dose recombinant tissue plasminogen activator (rtPA) therapy (0.6 mg/kg) for acute ischemic stroke (AIS) patients ≥ 80 years old, though most strokes occur in elderly people. The safety and effectiveness of this form of thrombolysis without endovascular therapy were evaluated in AIS patients ≥ 80 years old at our hospital. The data were collected from August 2006 to April 2010, before approval of the Mechanical Embolus Removal in Cerebral Ischemia (MERCI) retriever in Japan. Intravenous rtPA was administered to patients within 3 hours of stroke onset. The incidence of intracerebral hemorrhage (ICH), the recanalization rate of the occluded artery, and the modified Rankin Scale (mRS) score 3 months after stroke were examined. The patients who received rtPA therapy were stratified into two age groups: a younger group (< 80 years) and an older group (≥ 80 years). Of the 87 patients who received rtPA therapy, 17 (19.5%) were ≥ 80 years old. The incidence of symptomatic ICH was not significantly different between the younger (4.3%) and older (0%) groups (p = 0.61). The recanalization rate of the occluded artery was not significantly different between the younger (54%) and older (50%) groups (p = 0.78). The rate of an mRS score of 0–2, 3 months after stroke was significantly higher in the younger (44.3%) than in the older group (11.8%) (p = 0.013). Low-dose rtPA therapy appears to be as safe and feasible for AIS patients ≥ 80 years old as it is for younger people. This therapy should not be withheld because of age.

Effect of dural detachment on long-term tumor control for meningiomas treated using Simpson Grade IV resection

OBJECT Meningiomas treated by subtotal or partial resection are associated with significantly shorter recurrence-free survival than those treated by gross-total resection. The Simpson grading system classifies incomplete resections into a single category, namely Simpson Grade IV, with wide variations in the volume and location of residual tumors, making it complicated to evaluate the achievement of surgical goals and predict the prognosis of these tumors. Authors of the present study investigated the factors related to necessity of retreatment and tried to identify any surgical nuances achievable with the aid of modern neurosurgical techniques for meningiomas treated using Simpson Grade IV resection. METHODS This retrospective analysis included patients with WHO Grade I meningiomas treated using Simpson Grade IV resection as the initial therapy at the University of Tokyo Hospital between January 1995 and April 2010. Retreatment was defined as reresection or stereotactic radiosurgery due to postoperative tumor growth. RESULTS A total of 38 patients were included in this study. Regrowth of residual tumor was observed in 22 patients with a mean follow-up period of 6.1 years. Retreatment was performed for 20 of these 22 tumors with regrowth. Risk factors related to significantly shorter retreatment-free survival were age younger than 50 years (p = 0.006), postresection tumor volume of 4 cm(3) or more (p = 0.016), no dural detachment (p = 0.001), and skull base location (p = 0.016). Multivariate analysis revealed that no dural detachment (hazard ratio [HR] 6.42, 95% CI 1.41-45.0; p = 0.02) and skull base location (HR 11.6, 95% CI 2.18-218; p = 0.002) were independent risk factors for the necessity of early retreatment, whereas postresection tumor volume of 4 cm(3) or more was not a statistically significant risk factor. CONCLUSIONS Compared with Simpson Grade I, II, and III resections, Simpson Grade IV resection includes highly heterogeneous tumors in terms of resection rate and location of the residual mass. Despite the difficulty in analyzing such diverse data, these results draw attention to the favorable effect of dural detachment (instead of maximizing the resection rate) on long-term tumor control. Surgical strategy with an emphasis on detaching the tumor from the affected dura might be another important option in resection of high-risk meningiomas not amenable to gross-total resection.

Intramedullary recurrence of germinoma in the spinal cord 15 years after complete remission of a pineal lesion

The authors present a case of germinoma that was initially found in the pineal region and recurred 15 years later in the intramedullary cervical spinal cord after intensive chemo- and radiotherapy and diagnosis of complete remission. This 28-year-old man initially presented with seizures. Hydrocephalus and a pineal tumor were found on radiological examination, and partial resection of the tumor was performed. Histological diagnosis showed a pure germinoma. Following surgery, the patient received a combination of chemo- and radiotherapy, and a complete remission was shown. However, after 15 years of follow-up, he presented with gait disturbances. Spinal MRI showed an intramedullary mass lesion in the cervical spinal cord. The cervical lesion was biopsied, and histological examination again revealed a pure germinoma. With germinomas, the possibility of a drop metastasis from an intracranial lesion to the spinal cord must be considered during follow-up. However, in the present case, analysis of a CSF sample showed no abnormalities as in previously published cases. In recent years, multidisciplinary treatments have demonstrated good event-free survival rates in cases of pure germinomas, but long-term outcomes over the decades are not fully known. Continual follow-up of such cases is recommended even after complete remission has been achieved.

Stereotactic Radiosurgery for Intracranial Gliomas

This article presents an overview of stereotactic radiosurgery for intracranial glioma. It assists readers in reviewing up-to-date literature on this topic and determining indications of radiosurgery in the treatment of glioma. Discussion also includes its recent advances and future perspectives.

Role of endoscopic transnasal surgery for skull base chondrosarcoma: a retrospective analysis of 19 cases at a single institution

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.