Katsunobu Osato

Gamma knife treatment for multiple metastatic brain tumors compared with whole-brain radiation therapy.

The purpose of this paper was to note a potential source of error in magnetic resonance (MR) imaging. Magnetic resonance images were acquired for stereotactic planning for GKS of a vestibular schwannoma in a female patient. The images were acquired using three-dimensional sequence, which has been shown to produce minimal distortion effects. The images were transferred to the planning workstation, but the coronal images were rejected. By examination of the raw data and reconstruction of sagittal images through the localizer side plate, it was clearly seen that the image of the square localizer system was grossly distorted. The patient was returned to the MR imager for further studies and a metal clasp on her brassiere was identified as the cause of the distortion.A-60-year-old man with medically intractable left-sided maxillary division trigeminal neuralgia had severe cardiac disease, was dependent on an internal defibrillator and could not undergo magnetic resonance imaging. The patient was successfully treated using computerized tomography (CT) cisternography and gamma knife radiosurgery. The patient was pain free 2 months after GKS. Contrast cisternography with CT scanning is an excellent alternative imaging modality for the treatment of patients with intractable trigeminal neuralgia who are unable to undergo MR imaging.The authors describe acute deterioration in facial and acoustic neuropathies following radiosurgery for acoustic neuromas. In May 1995, a 26-year-old man, who had no evidence of neurofibromatosis Type 2, was treated with gamma knife radiosurgery (GKS; maximum dose 20 Gy and margin dose 14 Gy) for a right-sided intracanalicular acoustic tumor. Two days after the treatment, he developed headache, vomiting, right-sided facial weakness, tinnitus, and right hearing loss. There was a deterioration of facial nerve function and hearing function from pretreatment values. The facial function worsened from House-Brackmann Grade 1 to 3. Hearing deteriorated from Grade 1 to 5. Magnetic resonance (MR) images, obtained at the same time revealed an obvious decrease in contrast enhancement of the tumor without any change in tumor size or peritumoral edema. Facial nerve function improved gradually and increased to House-Brackmann Grade 2 by 8 months post-GKS. The tumor has been unchanged in size for 5 years, and facial nerve function has also been maintained at Grade 2 with unchanged deafness. This is the first detailed report of immediate facial neuropathy after GKS for acoustic neuroma and MR imaging revealing early possibly toxic changes. Potential explanations for this phenomenon are presented.In clinical follow-up studies after radiosurgery, imaging modalities such as computerized tomography (CT) and magnetic resonance (MR) imaging are used. Accurate determination of the residual lesion volume is necessary for realistic assessment of the effects of treatment. Usually, the diameters rather than the volume of the lesion are measured. To determine the lesion volume without using stereotactically defined images, the software program VOLUMESERIES has been developed. VOLUMESERIES is a personal computer-based image analysis tool. Acquired DICOM CT scans and MR image series can be visualized. The region of interest is contoured with the help of the mouse, and then the system calculates the volume of the contoured region and the total volume is given in cubic centimeters. The defined volume is also displayed in reconstructed sagittal and coronal slices. In addition, distance measurements can be performed to measure tumor extent. The accuracy of VOLUMESERIES was checked against stereotactically defined images in the Leksell GammaPlan treatment planning program. A discrepancy in target volumes of approximately 8% was observed between the two methods. This discrepancy is of lesser interest because the method is used to determine the course of the target volume over time, rather than the absolute volume. Moreover, it could be shown that the method was more sensitive than the tumor diameter measurements currently in use. VOLUMESERIES appears to be a valuable tool for assessing residual lesion volume on follow-up images after gamma knife radiosurgery while avoiding the need for stereotactic definition.This study was conducted to evaluate the geometric distortion of angiographic images created from a commonly used digital x-ray imaging system and the performance of a commercially available distortion-correction computer program. A 12 x 12 x 12-cm wood phantom was constructed. Lead shots, 2 mm in diameter, were attached to the surfaces of the phantom. The phantom was then placed inside the angiographic localizer. Cut films (frontal and lateral analog films) of the phantom were obtained. The films were analyzed using GammaPlan target series 4.12. The same procedure was repeated with a digital x-ray imaging system equipped with a computer program to correct the geometric distortion. The distortion of the two sets of digital images was evaluated using the coordinates of the lead shots from the cut films as references. The coordinates of all lead shots obtained from digital images and corrected by the computer program coincided within 0.5 mm of those obtained from cut films. The average difference is 0.28 mm with a standard deviation of 0.01 mm. On the other hand, the coordinates obtained from digital images with and without correction can differ by as much as 3.4 mm. The average difference is 1.53 mm, with a standard deviation of 0.67 mm. The investigated computer program can reduce the geometric distortion of digital images from a commonly used x-ray imaging system to less than 0.5 mm. Therefore, they are suitable for the localization of arteriovenous malformations and other vascular targets in gamma knife radiosurgery.

Glucose and methionine uptake and proliferative activity in meningiomas

Despite similar benign histological appearances, proliferative activity of meningiomas varies tumor to tumor, and even region to region in a tumor. To predict proliferative potential before surgery, we compared regional uptake of 2-[18F]fluoro-2-deoxyglucose ([18F]FDG) and L-[methyl-11C]methionine ([11C]MET) with histological indices of tumor proliferative activity in 17 specimens from six patients with meningioma obtained by PET guided stereotactic biopsies. Uptake of [11C]MET, an index of protein synthesis rate, significantly correlated not only with the count of nucleolar organizer regions (NORs), a histological index of protein synthesis, but also with Ki-67 index, a histological index of proliferative activity. On the other hand, [18F]FDG uptake showed no significant correlation with Ki-67 index or clinical malignancy. These results suggest that [11C]MET-PET is a useful tool for predicting tumor proliferative potential in meningiomas.

Identification of the small interstitial deletion at chromosome band 1p34–p35 and its association with poor outcome in oligodendroglial tumors

To narrow down the putative tumor‐suppressor gene locus and to assess the predictability of clinical courses by genomic alterations, we analyzed 46 oligodendroglial tumors for loss of heterozygosity (LOH) in the distal region of the short arm of chromosome 1. LOH at 1p was found in 43 tumors (93.5%), including all 28 oligodendrogliomas, all eight oligo‐astrocytomas, six of eight anaplastic oligodendrogliomas, and in one of two anaplastic oligo‐astrocytomas. Thirty‐seven tumors showed LOH patterns consistent with a large terminal deletion, whereas six tumors showed LOH suggesting interstitial deletions. Our data also showed two small regions of overlap at 1p34–p35 (∼5.7 Mb) and at 1p36.1–p36.2 (∼12 Mb). Among the six tumors with interstitial deletion, the proximal region was deleted in five tumors, whereas the distal region was deleted in only half of them. Overall, 91% of tumors showed deletion including this proximal region. To examine the clinical significance of the LOH pattern, the samples were classified into three groups: tumors without 1p LOH (Group 1, n = 3), tumors with an interstitial deletion (Group 2, n = 6), and tumors with a large terminal deletion (Group 3, n = 37). Both overall and progression‐free survival of patients in Group 2 was extremely poor compared with those included in Group 3 (P = 0.0006 and P = 0.003, respectively). As to the clinical response to chemotherapy, nimustine prevented tumor recurrence in Group 3 (P = 0.034) but not in Group 2. Our results demonstrate that a putative tumor‐suppressor gene(s) in oligodendroglial tumors is localized at 1p34–p35 and that small interstitial deletions, in contrast to large terminal deletions, are strongly predictive of both chemoresistance and aggressive characteristics of these tumors.

A rare case of metastatic renal cell carcinoma resembling a nerve sheath tumor of the cauda equina

We present a rare case of solitary metastasis to the cauda equina from the kidney. The patient was a 68-year-old man with a two-year history of low back pain. His past medical history revealed a renal cell carcinoma diagnosed seven years earlier. His lumbosacral MR imaging showed a well-demarcated, intradural extramedullary mass at the L3 level. He underwent an L2-4 laminectomy. The operative findings of the tumor quite resembled that of a nerve sheath tumor. It did not infiltrate into the subarachnoid space and involved only one spinal nerve. Pathology of the tumor was a metastasis of the renal cell carcinoma. Only 10 cases with such a metastasis to the cauda equina have been reported in the English literature. We added the 11th and reviewed the literature with reference to tumor pathologies, clinical findings and route of metastasis to the cauda equina.

Extraosseous accumulation of 99mTc phosphonate complexes in primary brain tumor evaluated with SPECT.

Although extraosseous accumulations of99mTc phosphate complexes are phenomena which can often be seen, no case showing extraosseous accumulation to brain tumor on SPECT has been reported. We report here two cases of primary brain tumor showing extraosseous accumulation of99mTc phosphate in bone SPECT.201Tl SPECT also showed increased201Tl uptake by the tumor. Comparing bone SPECT with201Tl SPECT, the regions of abnormality of both SPECTs were very similar in the case of glioblastoma, but in the case of malignant lymphoma the region showing intense uptake of99mTc-MDP was smaller than that on201Tl SPECT. It was revealed that bone SPECT is more useful in the assessment of extraosseous accumulation to a primary brain tumor than conventional bone scintigraphy.

Extraosseous accumulation of bone scanning agents in malignant brain tumors: Comparison to semi-quantitative evaluation with 99mTc SPECT/201Tl SPECT and histological findings

Although201Tl chloride (Tl) SPECT has been used in the differential diagnosis between recurrence of malignant brain tumor and necrosis after treatment, it is not generally recognized as a definite modality to distinguish them. We conducted a preliminary study using Tl SPECT and99mTc-MDP or99mTc-HMDP (Tc) SPECT because it has been said that extraosseous accumulation was caused by calcium deposits in necrotic tissues. In our study, for the purposes of clarifying the mechanism of extraosseous uptake and the correlation between extraosseous accumulation of bone-scanning agent and tumor viability in malignant brain tumors, we compared whether Tc uptake was correlated with the histopathological findings and further performed semi-quantitative evaluation between Tc SPECT and Tl SPECT. The correlation coefficients between the ratio of tumor to normal skull count obtained from Tc SPECT (Tc-T/N) and those of tumor to normal brain count (T/N) and to normal scalp count (T/S) both obtained from Tl SPECT were calculated. Using contrast enhanced CT (CECT) or contrast enhanced MRI (CE-MRI), 8 of 10 cases showed intensely ring-enhanced tumor with necrotic lesion. Histopathologically, 7 of 8 cases whose tumor had been resected before treatment had necrosis with increased vascularity or bleeding. Of the remaining 2 cases one case, malignant lymphoma had only hypervascularity by biopsy, while the other one was excluded for resection after treatment. Three of these 8 cases whose CE-CT or CE-MRI showed necrotic lesions exhibited Tc and Tl accumulations in the area corresponding to necrosis. In contrast, 2 showed no Tc nor Tl uptake. Tc-T/N had no significant correlation with any of early-, delayed-T/N or T/S. In conclusion, there was no significant correlation between Tc and Tl uptakes by malignant brain tumors in semiquantitative evaluation.

Topographical analysis of proliferating cells in meningiomas. Regional heterogeneity of the ability of tumors to proliferate

Regional heterogeneity of the ability of tumors to proliferate has been pointed out, but its topographical analysis has not been studied in detail. To evaluate the distribution of highly proliferating cells in totally resected meningiomas, seven cases (including one recurrent case) were investigated in this study. Immunostaining of PCNA was performed on the sections crossing the equator of the tumors. These sections were divided into multi-squares with sides of 500 micrometers. The proliferating potential was determined as the PCNA positive cell count in each square. By painting those squares in eight kinds of color corresponding to the value of the PCNA positive cell count, maps of proliferative ability were made. To predict the localization of proliferating cells, we studied these maps in relation to the following: MR image, calcification, distance from the dural attachment and distance from the tumor capsule. Maps of the PCNA positive cell count showed the intra-tumoral heterogeneity of proliferative ability in all cases. Most of the cases showed homogeneous enhancement on MRIs and these images could not be a predicting factor of the highly proliferating area. There was no significant relationship between the calcification and the PCNA positive cell count. Although the proliferating ability was not correlated with the distance from the dural attachment, inner regions distant from the capsule showed higher proliferative ability in all cases. From these results, one should be aware that the information from the samples of meningiomas do not reflect the proliferating ability of the whole tumor.