Hirohiko Nakamura

Gamma Knife Radiosurgery for Growth Hormone-Secreting Pituitary Adenomas Invading the Cavernous Sinus

The authors assessed whether gamma knife radiosurgery is effective for patients with acromegaly where the pituitary tumors invaded the cavernous sinus. Radiosurgery was performed on 9 patients (average of 20 Gy to the tumor margin), 8 of whom had already undergone transsphenoidal surgery and/or craniotomy with occasional medication of octreotide to reduce tumor size as well as hormonal levels. All tumors have been well controlled so far with follow-up periods ranging from 12 to 69 months (mean: 42). No complications occurred. Forty percent of the patients showed hormonal normalization at 2 years, with the median being 31 months. Similarly, 50% of the patients demonstrated normalization of GH and IGF-I at 36 months. We conclude that gamma knife radiosurgery is a safe and effective tool to treat these tumors invading the cavernous sinus.

Assessment of cerebral hemodynamics in childhood moyamoya disease using a quantitative and a semiquantitative IMP-SPECT study

BackgroundWe evaluated the cerebral hemodynamics in childhood moyamoya disease patients before and after surgery to assess both surgical indication and the effect of revascularization using single photon emission computed tomography (SPECT) study with N-isopropyl-p-l23I-iodoamphetamine (IMP). We compared results of quantitative and semi-quantitative SPECT studies to determine parameters by the semi-quantitative method to define severe hemodynamic ischemia.MethodsThere were 14 pediatric patients with moyamoya disease who suffered transient ischemic attacks (TIAs) in the anterior circulation. Before and after surgical revascularization by STA-MCA bypass and encephalomyosynangiosis (EMS), quantitative IMP-SPECT studies using the autoradiographic method (IMP-ARG method) were performed. Resting regional cerebral blood flow (rCBF) and regional vascular reserve (rVR) were measured in bilateral cortical territories (ROI) and cerebellum. Semi-quantitative parameters were calculated from the ratio of ROI counts to the dominant cerebellar counts (ROI/Ce ratio) at resting and acetazolamide-activated conditions.ResultsBefore surgery, the mean resting rCBF and rVR in bilateral ACA and MCA territories were less than 40 m//100 g/min and less than 10%, respectively, indicating severe hemodynamic ischemia. Except for the ACA territories, both the mean resting rCBF and mean rVR values in the entire cortex increased significantly after surgery (p < 0.05). By semi-quantitative studies, before surgery, the mean resting and acetazolamide-activated ROI/Ce ratios in bilateral ACA and MCA territories were less than 0.90 and 0.80, respectively. The mean resting and acetazolamide-activated ROI/Ce ratios increased significantly in the MCA territory after surgery. Severe hemodynamic ischemia, which categorized by the quantitative thresholds (resting rCBF < 40 m//100 g/min and rVR < 10%) was diagnosed by the semi-quantitative thresholds (resting ROI/ Ce ratio < 0.90 and acetazolamide-activated ROI/Ce ratio < 0.85), the sensitivity and specificity of which were 87.5% and 90.9%, respectively.ConclusionsThe cerebral hemodynamics in childhood moyamoya disease was improved entirely after surgery. Severe hemodynamic cerebral ischemia was diagnosed by not only quantitative but also semi-quantitative IMP-SPECT studies.

Apoptosis following Gamma Knife Radiosurgery in a Case of Acoustic Schwannoma

A 25-year-old woman with a large acoustic schwannoma underwent surgical excision 18 months after Gamma Knife radiosurgery because of transient expansion of the tumor causing ataxia. Histopathologial investigation by the TUNEL method revealed the presence of some apoptotic cells. The findings were compared with findings from a control group of 7 operated cases where radiosurgery had not been used. There was no apoptosis found in any of these cases. In addition, another case which resulted in a regrowing tumor following Gamma Knife treatment also showed no apoptosis. These findings suggest apoptosis may be a possible mechanism in reducing tumor size following Gamma Knife radiosurgery.

Gamma Knife Radiosurgery for Skull-Base Meningiomas

OBJECTIVE The primary purpose of this study was to evaluate the efficacy of gamma knife radiosurgery (GKRS) when used as a treatment modality for cavernous sinus or posterior fossa skull-base meningiomas (SBMs), with particular attention given to whether or not intentional partial resection followed by GKRS constitutes an appropriate combination treatment method for larger SBMs. PATIENTS AND METHODS Of the 101 SBM patients in this series, 38 were classified as having cavernous sinus meningiomas (CSMs), and 63 presented with posterior fossa meningiomas (PFMs). The patients with no history of prior surgery (19 CSMs, 57 PFMs) were treated according to a set protocol. Small to medium-sized SBMs were treated by GKRS only. To minimize the risk of functional deficits, larger tumors were treated with the combination of intentional partial resection followed by GKRS. Residual or recurrent tumors in patients who had undergone extirpations prior to GKRS (19 CSMs, 6 PFMs) are not eligible for this treatment method (due to the surgeries not being performed as part of a combination strategy designed to preserve neurological function as the first priority). RESULTS The mean follow-up period was 51.9 months (range, 6-144 months). The overall tumor control rates were 95.5% in CSMs and 98.4% in PFMs. Nearly all tumors treated with GKRS alone were well controlled and the patients had no deficits. Furthermore, none of the patients who had undergone prior surgeries experienced new neurological deficits after GKRS. While new neurological deficits appeared far less often in those receiving the combination of partial resection with subsequent GKRS, extirpations tended to be associated with not only a higher incidence of new deficits but also a significant increase in the worsening of already-existing deficits. CONCLUSION Our results indicate that GKRS is a safe and effective primary treatment for SBMs with small to moderate tumor volumes. We also found that larger SBMs compressing the optic pathway or brain stem can be effectively treated, minimizing any possible functional damage, by a combination of partial resection with subsequent GKRS.

A case of cervicomedullary junction tanycytic ependymoma associated with marked cyst formation

Tanycytic ependymomas are a subtype of ependymomas that were formally recognized as a new pathological entity in the latest World Health Organization (WHO) classification of 2000. They occur mostly in the spinal cord. Only a few reports have analyzed the proliferative potentials of these tumors; however, it has been reported that the MIB-1 labeling index of tanycytic ependymoma is lower than that of other subtypes of WHO grade II ependymomas. We report a rare case of cervicomedullary junction tanycytic ependymoma associated with marked cyst formation. A 62-year-old man had a history of progressive gait disturbance, diplopia, and swallowing disturbance over a one-month period prior to admission. Magnetic resonance imaging (MRI) showed a cystic mass with a mural nodule at the cervicomedullary junction with Gd-DTPA enhancement. Cyst-subarachnoid shunt was performed using a far lateral approach. After 6 years, however, the man was readmitted to the hospital because of reaccumulation of the cyst. Partial removal of a mural nodule and a cyst-subarachnoid shunt were performed simultaneously by a midline suboccipital approach. The pathological diagnosis was tanycytic ependymoma. Postoperatively, the patient recovered well and was discharged from the hospital without further treatment. Most of the tumor cells had small, round nuclei; pleomorphism was minimal. The cytoplasm was dilated. The tumor cells were positive for EMA and s-100, and negative for CD-34. GFAP was not determined due to difficulty caused by background glial processes. The MIB-1 labeling index was less than 1%. Ultrastructurally, the tumor cells had ependymal cell features, such as desmosomes and microvilli. Based on these findings, the pathological diagnosis was tanycytic ependymoma.

Clinicopathologic Study of Pineal Parenchymal Tumors of Intermediate Differentiation

OBJECTIVE Pineal parenchymal tumors of intermediate differentiation (PPTID) are extremely rare tumor entities, and only limited data are available regarding their pathologic features and biologic behaviors. Because grading criteria of pineal parenchymal tumors (PPTs) have yet to be established, the treatment strategy and prognosis of PPTIDs remain controversial. We describe the clinicopathologic study of six patients with PPTID and compare responses for the treatment and prognosis with cases of pineocytoma (PC) and pineoblastoma (PB). From this analysis, we attempt to clarify the treatment strategy for PPTIDs. METHODS This study included 15 patients with PPTs, consisting of 6 PCs, 6 PPTIDs, and 3 PBs. We focused on the 6 patients with PPTIDs. All PPTID cases were treated surgically, and radiotherapy and chemotherapy were administered as adjuvant therapies in some cases. We have earlier reported the histopathologic study (Neuropathology 32:647-653, 2012). Briefly, we examined mitotic figures and necrosis by hematoxylin-eosin staining and immunohistochemical markers such as neuronal markers (synaptophysin, neurofilament (NF), and neuronal nuclear antigen), and an MIB-1 labeling index was determined. RESULTS In the PPTID cases, the extent of resection was variable and the recurrence rates among patients varied according to stage and treatment. All PC patients underwent total resection with no recurrence. All PB patients underwent resection and adjuvant therapy with radiotherapy and chemotherapy. There were no recurrences in patients with PC or PB. The results of histopathologic findings have been already reported as mentioned above. Briefly, the results indicated no mitotic figure or necrosis in any of the six cases of PPTID, but those features were observed in PB cases. All cases even including PC and PB were immunopositive for neuronal markers. The MIB-1 labeling index of PPTID was 3.5%, whereas it was 0% in PC and 10.5% in PB. CONCLUSIONS Good radiosensitivity of PPTIDs was observed in our series. Because there are cases with discrepancies between images and pathologic findings, it is very difficult to determine the proper treatment strategy for PPTIDs. Proliferative potential was correlated with World Health Organization grade, although the immunoreactivity of neuronal markers did not correlate with the histologic grade.

A case of tanycytic ependymoma arising from the cerebral hemisphere

We report a rare case of tanycytic ependymoma arising from the cerebral hemisphere. A 59-year-old man was admitted to our hospital because of the incidental detection by MRI of a tumor lesion in the right temporooccipital paratrigonal region. The mass showed low-to iso-intensity on T1-weighted images and high intensity on T2/proton-weighted images. Partial resection was performed using a transsulcal approach to avoid compromising the visual field. Most of the tumor cells showed elongated spindle shapes arranged in dense fascicles. A few true ependymal rosettes and perivascular pseudorosettes were visible. The tumor cells were positive for GFAP, S-100, and vimentin, but negative for synaptophysin, EMA, and keratin. The MIB-1 labeling index was approximately 1%. Ultrastructurally, the tumor cells had ependymal cell features, such as microvilli and cilia. From these findings, a pathological diagnosis of tanycytic ependymoma was made.

Radiation-induced osteosarcomas after treatment for frontal gliomas: a report of two cases.

Most radiation-induced osteosarcomas of the skull are reported to arise in the facial bone or paranasal sinus after radiotherapy for retinoblastoma and/or pituitary adenoma. Here we report two cases of radiation-induced osteosarcoma in the paranasal sinus after treatment for frontal glioma. Case 1 was a 56-year-old woman who underwent surgical resection of a left frontal tumor in October 1990. The histological diagnosis was a low-grade glioma, and radiotherapy of 54 Gy was administered. Sixteen years later, in September 2006, the patient noted an enlarging subcutaneous mass in the right frontal region. CT showed an osteolytic mass in the right frontal sinus. An open biopsy established the histopathological diagnosis of osteosarcoma, and the patient subsequently died of rapid tumor regrowth. Case 2 was a 58-year-old man who underwent partial removal of a bifrontal tumor in May 1996. The histological diagnosis was anaplastic oligoastrocytoma, and radiotherapy of 56 Gy was administered. Twelve years later, in March 2008, the patient was readmitted to our hospital for reasons of marked deterioration in general physical condition. Tumor recurrence was suspected in the left frontal lobe, and CT demonstrated an osteolytic mass in the left frontal and ethmoid sinus. A secondary operation was performed, and the pathological specimens were diagnosed as osteosarcoma. Radiotherapy was readministered, but the subject died of rapid tumor regrowth. From these clinicopathological findings, both cases were diagnosed as radiation-induced osteosarcoma. Radiation-induced osteosarcomas appeared 16 and 12 years after radiotherapy in cases 1 and 2, respectively. As the prognosis of radiationinduced osteosarcoma is poorer than that of primary osteo-sarcoma, careful attention is required for consideration of the long-term survival of patients with glioma.

Cortical neuron loss in post-traumatic higher brain dysfunction using (123)I-iomazenil SPECT.

In patients with higher brain dysfunction (HBD) after mild traumatic brain injury (MTBI), diagnostic imaging of cortical neuron loss in the frontal lobes was studied using SPECT with (123)I-iomazenil (IMZ), as a radioligand for central benzodiazepine receptor (BZR). Statistical imaging analysis using three-dimensional stereotactic surface projections (3D-SSP) for (123)I-IMZ SPECT was performed in 17 patients. In all patients with HBD defined by neuropsychological tests, cortical neuron loss was indicated in the bilateral medial frontal lobes in 14 patients (83 %). A comparison between the group of 17 patients and the normal database demonstrated common areas of cortical neuron loss in the bilateral medial frontal lobes involving the medial frontal gyrus (MFG) and the anterior cingulate gyrus (ACG). In an assessment of cortical neuron loss in the frontal medial cortex using the stereotactic extraction estimation (SEE) method (level 3), significant cortical neuron loss was observed within bilateral MFG in 9 patients and unilateral MFG in 4, and bilateral ACG in 12 and unilateral ACG in 3. Fourteen patients showed significant cortical neuron loss in bilateral MFG or ACG. In patients with MTBI, HBD seemed to correlate with selective cortical neuron loss within the bilateral MFG or ACG where the responsible lesion could be. 3D-SSP and SEE level 3 analysis for (123)I-IMZ SPECT could be valuable for diagnostic imaging of HBD after MTBI.

[Clinicopathological Study of Pilomyxoid-Spectrum Astrocytomas:An Analysis of the BRAF Gene. Report of Two Cases].

In contrast to pilocytic astrocytomas(PAs), pilomyxoid astrocytomas(PMAs)demonstrate monophasic piloid cells with angiocentric distribution and a more aggressive clinical course. Recently, several reports have described combined histological features of both subtypes;accordingly, these were termed intermediate pilomyxoid tumors(IPTs). The KIAA1549-BRAF fusion gene has been found in approximately 70% of PAs, but is reportedly rare in PMAs. We describe a clinicopathological study of two patients with pilomyxoid-spectrum astrocytoma(PMSA). Case 1 was of a 29-year-old man who presented with a generalized seizure. Gadolinium-magnetic resonance imaging(Gd-MRI)demonstrated a less enhanced tumor in the left temporal lobe. Case 2 was of a 9-year-old boy who presented with headache. Gd-MRI revealed an irregularly enhanced tumor in the left cerebellum. In Case 1, the tumor showed monomorphous bipolar cells in a myxoid background and angiocentric arrangement;therefore, the diagnosis was PMA. In Case 2, part of the tumor had a myxoid, angiocentric pattern characteristic of PMA;the other part had a biphasic pattern characteristic of PA. PMA and PA were mixed in a 7:3 ratio;therefore, IPT was diagnosed. No BRAF V600E mutations were found by immunohistochemistry and sequencing in either case. Three major KIAA1549-BRAF fusion subtypes were analyzed by quantitative reverse transcription polymerase chain reaction(RT-PCR)and sequencing. No fusions were found in Case 1. However, K16-B9 fusion was identified in Case 2, and this fusion was more prevalent in the PA component than in the PMA component. In summary, no BRAF V600E mutations were found in PMSAs, but KIAA1549-BRAF fusion was identified in IPT, particularly in the PA component.