Yuuta Kamoshima

Role of surgery for optic pathway/hypothalamic astrocytomas in children

Optic pathway/hypothalamic pilocytic astrocytomas in children are usually treated with chemotherapy following a surgical biopsy. In this report, we retrospectively considered the role of surgical intervention. In a series of 25 patients without neurofibromatosis type 1, the median age at initial treatment was 3.1 years (range, 0-15 years). Twenty cases were verified by histology, and five cases were diagnosed by MRI findings. Twenty-three patients received chemotherapy. All patients were alive at median follow-up of 66 months. Aims of surgery at the initiation of treatment were biopsy in 12 cases (1 stereotactic and 11 craniotomies) and debulking in 7 cases. The 11 open biopsies revealed pilocytic astrocytoma; however, noticeable complications occurred in five children after the biopsies. Review of preoperative MRIs showed that all had typical findings indicating pilocytic astrocytoma. The open biopsy offered no noteworthy benefit for the patients despite surgical risk and delay of chemotherapy. The extent of the seven resection surgeries was 70% or less removal, and postoperative adjuvant therapy was needed for six of the seven patients. The remaining six children who did not undergo surgery obtained remission with chemotherapy alone. After relapse in nine patients, 15 bulk-reduction surgeries were performed. Surgical resection was not curative in any patient. In five patients, mostly older children, cystic expansion of tumor was partially resected, resulting in additional remission. In conclusion, considering the risk of open surgery and the effectiveness of chemotherapy, the role of surgical intervention is restricted to bulk-reduction surgery only when it is inevitable, especially at relapse after chemotherapy.

Update on current standard treatments in central nervous system germ cell tumors.

PURPOSE OF REVIEW Various approaches have been used for the management of patients with germ cell tumors (GCTs) in the central nervous system (CNS); however, the optimal treatment of both germinoma and nongerminomatous GCTs remains unknown. This review discusses current management strategies and late effects of therapy for CNS GCTs. RECENT FINDINGS To reduce the late complications of radiation therapy for patients with germinoma, many investigators have introduced dose reduction of radiation therapy in association with platinum-based chemotherapy. In addition, the radiation field has been restricted to the whole ventricular area for localized germinoma. This type of combination therapy has shown promising results and preserves cognitive function and quality of life. Despite various approaches including high-dose chemotherapy against highly malignant or relapsed GCTs, the prognoses of these patients remain dismal except for a few successful reports. SUMMARY The 10-year survival rate of CNS germinoma is approximately 90%. Most patients with CNS GCTs are children and young adults. Therefore, with the improving life prognosis of young patients, secondary neoplasms, secondary cerebral vasculopathy, neurocognitive deficits, and many other adverse effects induced by the initial treatments are problems to be solved in the next decade.

Type 1 collagen as a potential niche component for CD133‐positive glioblastoma cells

Cancer stem cells are thought to be closely related to tumor progression and recurrence, making them attractive therapeutic targets. Stem cells of various tissues exist within niches maintaining their stemness. Glioblastoma stem cells (GSCs) are located at tumor capillaries and the perivascular niche, which are considered to have an important role in maintaining GSCs. There were some extracellular matrices (ECM) on the perivascular connective tissue, including type 1 collagen. We here evaluated whether type 1 collagen has a potential niche for GSCs. Imunohistochemical staining of type 1 collagen and CD133, one of the GSCs markers, on glioblastoma (GBM) tissues showed CD133‐positive cells were located in immediate proximity to type 1 collagen around tumor vessels. We cultured human GBM cell lines, U87MG and GBM cells obtained from fresh surgical tissues, T472 and T555, with serum‐containing medium (SCM) or serum‐free medium with some growth factors (SFM) and in non‐coated (Non‐coat) or type 1 collagen‐coated plates (Col). The RNA expression levels of CD133 and Nestin as stem cell markers in each condition were examined. The Col condition not only with SFM but SCM made GBM cells more enhanced in RNA expression of CD133, compared to Non‐coat/SCM. Semi‐quantitative measurement of CD133‐positive cells by immunocytochemistry showed a statistically significant increase of CD133‐positive cells in Col/SFM. In addition, T472 cell line cultured in the Col/SFM had capabilities of sphere formation and tumorigenesis. Type 1 collagen was found in the perivascular area and showed a possibility to maintain GSCs. These findings suggest that type 1 collagen could be one important niche component for CD133‐positive GSCs and maintain GSCs in adherent culture.

Immunohistochemical evaluation of O6‐methylguanine DNA methyltransferase (MGMT) expression in 117 cases of glioblastoma

Temozolomide (TMZ) is an oral alkylating agent which is widely used in the treatment of glioblastoma (GBM) and is composed of astrocytic and/or oligodendroglial tumors, and the evaluation of O6‐methylguanine DNA methyltransferase (MGMT) expression is important to predict the response to TMZ therapy. In this study, we conducted immunohistochemical analysis of 117 cases of Japanese GBM including 19 cases of GBM with oligodendroglioma component (GBMO), using a scoring system for quantitative evaluation of staining intensity and proportion of MGMT, and performed survival analysis of these patients. Immunohistochemically, 55 cases (47%) were positive for MGMT with various intensities and proportions (total score (TS) ≥ 2), while 62 cases (53%) were negative (TS = 0). The distribution of MGMT expression pattern was not affected by any clinicopathological parameters such as the histological subtype (GBM vs. GBMO), age and gender. The survival analysis of these patients revealed that the minimal expression of MGMT (TS ≥ 2) was a significant unfavorable prognostic factor (P < 0.001) as well as resectability (P = 0.004). Moreover, multivariate analysis showed that minimal MGMT expression in GBM was the most potent independent predictor for progression free survival (P < 0.001) and also overall patient survival (P < 0.001). This is the first report employing the scoring system for both staining intensity and proportion to evaluate immunohistochemical MGMT expression in GBM. In addition, our results emphases the clinicopathological values of the immunohistochemical approach for MGMT expression in glioma patients as a routine laboratory examination.

Frontofacial monobloc advancement using gradual bone distraction method

For children with craniosynostosis presenting intracranial hypertension and facial hypoplasia, different techniques have been used. Commonly, an initial frontoorbital advancement to expand a tight cranium volume was followed by Le Fort III osteotomy to repair midface abnormalities several months later. The 2-stage surgeries were unified into a 1-step procedure to optimize treatment. We here report results of frontofacial monobloc advancement, applying gradual distraction by a rigid external distraction device. Three patients were treated with excellent functional and cosmetic outcome with high rate of patient satisfaction. There was no remarkable complication.

Chemotherapy with Cisplatin and Vincristine for Optic Pathway/ Hypothalamic Astrocytoma in Young Children

OBJECTIVE Optic pathway/hypothalamic astrocytomas (OPHA) in young children often show accelerated growth and require rather intensive induction chemotherapy. METHODS Fifteen children (median age: 3 years) with a large OPHA were treated. All of them presented with progressive disease, and the tumor size was larger than 34 mm. Pilocytic astrocytoma was confirmed histologically in 10 patients. Eleven patients had visual disturbance, six had diencephalic syndrome and four had hydrocephalus. RESULTS The children received six to eight cycles of cisplatin (20 mg/m(2): days 1-5) and vincristine (1.4 mg/m(2): days 1, 8, 15), every 4 weeks. Objective response was obtained in 11 patients (73%); one complete response, eight partial responses and two minor responses. Although the remaining four cases were evaluated as stable disease, all tumors decreased in volume. All children tolerated the chemotherapy well under careful audiological monitoring. CONCLUSION Although the present series was small, this chemotherapy is a useful regimen for induction therapy in children with an aggressive deep-seated pilocytic astrocytoma.

Morphological and histological changes of glioma cells immediately after 5-aminolevulinic acid mediated photodynamic therapy

Abstract Objective: Photodynamic therapy (PDT) using 5-aminolevulinic acid (5-ALA) is a new therapeutic modality for malignant glioma. This study is designed to evaluate acute morphological and histological changes of glioma cells after 5-ALA mediated PDT using fluorescence microscopy and three-dimensional spheroid models. Methods: Monolayer cultures and spheroids (small and large sizes) of C6 (rat glioma cell line) and U251MG (human glioma cell line) cells were co-incubated for 4 hours with 5-ALA (100 μg/ml) and irradiated using a diode laser (635±5 nm, 5-100 mW/cm2, and total light dose 2·5-50 J/cm2). Growth kinetics of the spheroids were followed for 7 days after PDT and morphological changes were assessed by phase contrast microscopy. In addition to hematoxylin and eosin and the terminal deoxynucleotidyl transferase-mediated dUTP-FITC nick end-labeling, various fluorescent dyes including calcein AM, ethidium homodimer-1 (EthD-1), annexin V-FITC, propidium iodide and Hoechst 33342, were used to clarify the mechanism of cell death after PDT. Results: Although PDT spheroids of both cell lines showed growth inhibition during the first few days, resumption of spheroid growth on day 3 after irradiation was observed in most spheroids. Hematoxylin and eosin staining showed cells with condensed chromatin within the superficial layer of the PDT spheroids. In the PDT groups, monolayer cells in the irradiated area were negative for calcein AM and clearly positive for EthD-1. In C6 PDT spheroids, the outer layer of the spheroid was negative for calcein AM and positive for EthD-1. In monolayer cells, cells in the irradiation area in PDT groups were positive for propidium iodide and negative for Hoechst 33342. Conclusion: Light and fluorescence microscopic findings suggested necrotic cell death as an anti-tumor effect in the acute phase after PDT. These findings were observed in both C6 and U251MG monolayer culture cells and spheroids. Although various total light doses resulted in significant differences in the growth rate of spheroids after PDT, resumption of spheroid growth occurred in most spheroids.

Radiation induced intraparenchymal meningioma occurring 6 years after CNS germinoma: Case report

Meningioma represents approximately 15% of primary intracraial tumors in adults. However, intraparenchymal meningiomas ithout dural attachment that are surrounded by brain tissue are are and have been reported only occasionally in the literature [5]. n the other hand, secondary meningiomas attributable to radioherapy represent a separate clinical entity and have been reported s more likely to be histologically atypical, multiple, and result in a oor clinical outcome [3,4]. So far in these previous reports, there is no report related to econdary intraparenchymal meningiomas occurring in a radiation eld for primary brain tumor. In this paper, the authors present the case of a 20-year-old urvivor of a childhood central nervous system (CNS) germinoma ho developed a progressively enlarging intraparenchymal meninioma occurring in an area that had previously received radiation t a pediatric age.

Giant Frontal Mucocele Occurring 32 Years after Frontal Bone Fracture: A Case Report

Giant mucoceles of the frontal sinus are rare but their recognition is important in the differential diagnosis of proptosis and fronto-orbital lesions. The authors describe a patient with frontal giant mucocele with intracranial as well as orbit and ethmoid sinus involvement. Thirty-two years after a frontal sinus fracture, a 51-year-old female presented with headache, and left exophthalmos and ophthalmoplegia. Computed tomography and magnetic resonance imaging demonstrated a giant frontal sinus mucocele with extension into the left anterior cranial fossa. The mucocele was treated with a transcranial and endoscopic transnasal approach. The frontal sinus was then cranialized with reconstruction of the posterior wall, and finally a wide nasal drainage was performed. The clinical symptoms disappeared immediately after surgery.

[Risk Factors for Adverse Events after Implantation of BCNU Wafers in High-grade Gliomas].

BACKGROUND In Japan, patients with malignant glioma have been treated with BCNU wafers (Gliadel®) since January 2013. Several adverse events(AEs)associated with implantation of BCNU wafers, including cerebral edema or cyst formation, are recognized. Here, we report a retrospective review of the experience with implantation of BCNU wafers in our institutions and our findings regarding the risk factors for the AEs. METHODS We reviewed the records of patients with malignant glioma who were implanted with BCNU wafers between April 2013 and September 2014. Their AEs were examined clinically and radiologically and evaluated according to Common Terminology Criteria for Adverse Events (CTCAE) grading. For investigating the association between risk factors and incidence of AEs, histological diagnosis, extent of resection, and period of BCNU wafers implantation surgery were selected as possible risk factors. RESULTS Twenty-one patients were included in this investigation. There were no associations among incidence of AEs and histological diagnosis or extent of tumor resection. However, regarding the period of BCNU wafers implantation, additional resection for newly diagnosed tumors and resection for recurrent tumors tended to increase the rate and severity of AEs, especially cerebral edema, compared to primary resection. CONCLUSION In cases of BCNU wafers implantation, the incidence and degree of AEs might increase if additional resection for newly diagnosed tumors or resection for recurrent tumors is performed. Our investigation revealed that AEs associated with implantation of BCNU wafers tend to occur in the repeated glioma surgery.