Yoshiteru Miyajima

Fluorescence-guided resection of metastatic brain tumors using a 5-aminolevulinic acid-induced protoporphyrin IX: pathological study

We performed a pathological study to identify the locus of production of protoporphyrin IX (PPIX) in human metastatic brain tumors. Patients with metastatic brain tumors (n = 11) received 1 g of 5-aminolevulinic acid (5-ALA) perorally 2 h before undergoing surgery. The target region was exposed to laser light with a peak wavelength of 405 ± 1 nm and an output of 40 mW. Tissue samples from the tumor bulk and surrounding areas were examined by histological and fluorescence methods. Of the 11 tumors, 9 manifested PPIX fluorescence in the tumor bulk and peritumoral brain tissue. Our findings indicate that PPIX fluorescence can be observed in peritumoral edematous areas that are free of neoplastic cells, because PPIX produced by neoplastic cells leaks into the surrounding edematous area.

Expression of autocrine motility factor mRNA is a poor prognostic factor in high-grade astrocytoma

It has been reported that tumor infiltration is correlated with the expression of autocrine motility factor (AMF) and its receptor 78 kDa glycoprotein (gp78). The purpose of the present study was to detect AMF and gp78 mRNA expression levels and their localization in high‐grade astrocytomas (glioblastoma and anaplastic astrocytoma) and to determine whether AMF and gp78 are important prognostic factors. A total of 32 formalin‐fixed and paraffin‐embedded glioblastomas and 23 formalin‐fixed and paraffin‐embedded anaplastic astrocytomas was used. The expressions of AMF and gp78 mRNA were detected using the highly sensitive in situ hybridization method. The expression of AMF mRNA was detected in 27 of 32 glioblastomas (84.4%) and 11 of 23 anaplastic astrocytomas (47.8%). The positivity of AMF mRNA was significantly higher in glioblastomas than in anaplastic astrocytomas (P = 0.0094), but gp78 mRNA was detected in most cases and no statistical significance was observed. The overall survival of patients with AMF expression was significantly shorter than patients without AMF expression (P = 0.0175). In anaplastic astrocytomas, the overall survival of patients with AMF expression was also significantly shorter than in patients without AMF expression (P = 0.0058). This study demonstrated that AMF is a poor prognostic factor in high‐grade astrocytomas.

Utility of intraoperative fluorescent diagnosis of residual hemangioblastoma using 5-aminolevulinic acid.

Hemangioblastoma is a benign tumor of the cerebellum, and treatment involves surgical excision, both as the initial treatment and also in case of recurrence. Recurrence of hemangioblastoma can be local due to incomplete resection or can be distant and separate from the tumor resection region. Local recurrence can largely be avoided by verifying for any residual tumor intraoperatively before closure. In this study, we used intraoperative fluorescent diagnosis using 5-aminolevulinic acid (5-ALA) to verify the presence of a residual tumor during surgical resection. Nine patients with hemangioblastoma were given 1 g of 5-ALA orally before surgery, and a laser beam of 405 nm was focused on the tumor during resective surgery. Fluorescence of protoporphyrin IX (PPIX) was observed in the core of tumor in all the cases. Fluorescence of PPIX was observed in the peritumoral cyst wall in two patients after tumor resection, and in both of them fluorescent parts of PPIX were resected and histological examination showed tumor cells. Usually, there are no tumor cells in the peritumoral cyst of a hemangioblastoma, yet hemangioblastomas may sometimes recur from an unresected cyst wall. It is thus necessary to excise an infiltrating cyst of tumor cells to prevent recurrence. Intraoperative fluorescent diagnosis using 5-ALA is a useful method to discern whether tumor cells are present in the peritumoral cyst wall of a hemangioblastoma.

Chronic Phase Intracranial Hemorrhage Caused by Ruptured Pseudoaneurysm Induced by Carmustine Wafer Implantation for Insulo-opercular Anaplastic Astrocytoma: A Case Report

Carmustine wafers improve the survival of patients with high-grade gliomas, but several adverse events have been reported. A 42-year-old man with left insulo-opercular anaplastic astrocytoma developed a massive intra-cavital hematoma with subarachnoid hemorrhage caused by ruptured pseudoaneurysm of the left middle cerebral artery (MCA) adjacent to the site of carmustine wafers implanted 6 months previously. Intraoperative finding demonstrated a dissection of the insular portion of the MCA, and pathological examination identified the resected pseudoaneurysm. This case demonstrates that carmustine wafers can cause changes in local vessels. Therefore, implantation of carmustine wafers near to important vessels passing close to the resection cavity should be considered with great caution.

A De Novo Mouse Model of C11orf95-RELA Fusion-Driven Ependymoma Identifies Driver Functions in Addition to NF-κB

SUMMARY The majority of supratentorial ependymomas (ST-ependymomas) have few mutations but frequently display chromothripsis of chromosome 11q that generates a fusion between C11orf95 and RELA (RELAFUS). Neural stem cells transduced with RELAFUS ex vivo form ependymomas when implanted in the brain. These tumors display enhanced NF-κB signaling, suggesting that this aberrant signal is the principal mechanism of oncogenesis. However, it is not known whether RELAFUS is sufficient to drive de novo ependymoma tumorigenesis in the brain and, if so, whether these tumors also arise from neural stem cells. We show that RELAFUS drives ST-ependymoma formation from periventricular neural stem cells in mice and that RELAFUS-induced tumorigenesis is likely dependent on a series of cell signaling pathways in addition to NF-κB.

Effectiveness of interferon-beta therapy for recurrent glioblastoma: a case report

AIMS AND BACKGROUND Glioblastoma has a poor prognosis, with few therapeutic options if it recurs. We report a case in which we were able to inhibit the growth of a recurrent glioblastoma by weekly single-dose administration of interferon-beta. CASE REPORT A patient with recurrent glioblastoma after radiation and chemotherapy was treated with nimustine and interferon-beta. After 2 cycles of nimustine, the patients leukocyte, neutrophil, and platelet counts showed grade 4 toxicity according to the National Cancer Institutes Common Toxicity Criteria. The patient was treated with a weekly single dose of interferon-beta at 6 x 10(6) IU. The tumor showed no remarkable changes after 18 months, and the patients Karnofsky performance status remained at 50%. CONCLUSIONS The administration of interferon-beta produced long-term control in one case of glioblastoma and may be an effective therapy.

Usefulness of gamma knife pituitary surgery to control thalamic pain after treatment of thalamic malignant lymphoma and report of pathology of gamma knife lesions

Here, we describe the first reported autopsy findings following gamma knife surgery for thalamic pain. A 62-year-old man presented with thalamic pain after treatment for thalamic malignant lymphoma. He was treated with narcotic drugs, but his pain was uncontrollable. Treatment using gamma knife surgery on the pituitary gland using a maximum dose of 180 Gy, led to the control of his intractable pain with lower doses of drugs. His death was pain-free and was caused by a recurrence of the tumor, six months after gamma knife surgery. An autopsy was performed and necrosis was present in the area of the pituitary gland where it borders the pituitary stalk. Half of the adenohypophysis was not necrotic, and necrosis was not found in the pituitary stalk.