Japanese Journal of Neurosurgery
Online ISSN : 2187-3100
Print ISSN : 0917-950X
ISSN-L : 0917-950X
Volume 23 , Issue 7
Showing 1-9 articles out of 9 articles from the selected issue
SPECIAL ISSUES Frontiers in Basic and Clinical Oncology of Gliomas
  • Koichi Ichimura, Hideyuki Arita, Yoshitaka Narita
    2014 Volume 23 Issue 7 Pages 532-540
    Published: 2014
    Released: July 25, 2014
      Recent large-scale genome analyses have led to the discovery of several novel key genes in gliomas such as IDH1/2, CIC and ATRX. Mutations of these newly identified genes appear to play a very critical role in the development of various subtypes of adult gliomas, by working in collaboration with other genes that have been discovered over the last few decades. The latest additions are the TERT promoter mutations. They occur at one of the two hotspots within the promoter region of TERT, the reverse-transcriptase subunit of telomerase, and upregulate TERT expression. The current understanding of the order of events is as follows : both astrocytomas and oligodendrogliomas (WHO grade II-III) develop through the acquisition of IDH mutations, possibly from common precursor cells. When TP53 and ATRX mutations subsequently occur they may become astrocytomas. When 1p19q loss is present, TERT promoter mutations and CIC mutations occur ; this may lead to oligodendrogliomas. Glioblastomas mostly develop without IDH mutations and rarely have 1p19q loss. Instead they harbor simultaneous inactivation of the RB1 and p53 pathways, mostly by means of CDKN2A homozygous deletions, as well as alterations of the MAPK and/or PI3K pathways, typically by EGFR amplification and/or PTEN mutations, and TERT promoter mutations in addition. These subtype-specific genetic changes make it possible to molecularly sub-classify adult gliomas using a combination of only a few genes. Although this has conventionally been done with IDH mutations and 1p19q loss, it is now suggested that the TERT promoter status may have an additional, if not superior, role for this purpose. A future outcome-based prospective study will help establish a robust molecular diagnostic system for gliomas that incorporates objectivity and precision.
    Download PDF (459K)
  • Hideyuki Saya, Shunsuke Shibao, Oltea Sampetrean
    2014 Volume 23 Issue 7 Pages 541-546
    Published: 2014
    Released: July 25, 2014
      Gliomas are a group of primary brain neoplasms classified mainly on the basis of their morphological resemblance to glial cells. Their most malignant form, grade IV glioma or glioblastoma multiforme, continues to remain lethal, partly due to a pronounced intratumoral heterogeneity which prevents effective therapeutic targeting. The heterogeneity seen in glioblastomas ranges from multiple genetic and epigenetic alterations to a cellular diversity that has recently been traced to the existence of tumor stem cells.
      Glioma stem cells, like other types of cancer stem cells, have the ability to self-renew and differentiate into multiple tissue-specific lineages. They can therefore maintain and propagate the tumor by continuously giving rise to a variety of malignant offspring and also initiate tumor recurrence from a very small number of cells. Furthermore, they are also considered to be the cells most likely to survive even multi-modality treatments, due to characteristics such as slow cycling or quiescence, high drug efflux capacity and strong antioxidant and immune defense systems.
      With the addition of each new research finding, the concept of glioma stem cell itself continues to evolve. However, many aspects of glioma stem cell biology are still insufficiently understood. It is not known which cells they originate from, what their relationship to normal tissue stem cells is and what mechanisms or events underlie their malignant transformation. Furthermore, whether the answers to these questions are the same for all glioma stem cells is also a matter that requires further investigation.
      This review focuses on our current understanding of glioma stem cells, the signaling pathways behind their pathogenic features and their role in glioma biology. We also discuss possible answers to the questions mentioned above, in the context of knowledge obtained from the study of tumor stem cells of several other types of malignancies. Finally, we review the importance of glioma stem cells in treatment resistance in glioblastoma and the implications of stem cell-specific targeting strategies.
    Download PDF (637K)
  • Hikaru Sasaki
    2014 Volume 23 Issue 7 Pages 547-558
    Published: 2014
    Released: July 25, 2014
      The approval of BCNU wafers and bevacizumab (BEV) has widened the therapeutic options for malignant glioma patients. Although these new drugs contribute to improve disease management in patients, there are some pitfalls associated with the use of these new drugs. On the other hand, the recent reports of the results of the randomized trials on anaplastic oligodendroglioma (AO) and elderly glioblastoma (GB) have significant impact on clinical practice. In this review, we discuss the risks and benefits of the two new drugs, as well as the updated standard treatment for AO and elderly GB.
      Local chemotherapy with BCNU wafers offered a survival benefit to patients with recurrent as well as newly diagnosed malignant gliomas. BEV monotherapy was associated with a decrease in tumor volume as defined by contrast enhancement in the majority of the recurrent glioblastomas. The addition of BEV to radiotherapy (RT) /temozolomide (TMZ) for newly diagnosed glioblastoma patients improved progression-free survival (PFS) but not overall survival (OS). The analyses of two phase III clinical trials from the 1990's with long-term follow-up have shown that early administration of chemotherapy improved the OS of patients with anaplastic oligodendroglial tumors harboring a 1p19q co-deletion. Moreover, two phase III clinical trials with elderly glioblastoma patients have shown that MGMT promoter methylation predicts increased OS for patients treated with TMZ monotherapy.
      The recent approval of new drugs are encouraging. However, to fully benefit from these drugs, neuro-oncologists should correctly understand the results of the relevant clinical trials and be well aware of the possible risks. Current evidence suggests that molecular studies should be included in routine diagnostic procedures.
    Download PDF (1874K)
  • Tadashi Nariai
    2014 Volume 23 Issue 7 Pages 559-568
    Published: 2014
    Released: July 25, 2014
      It has now been well recognized that morphological imaging is not enough to evaluate the biological nature of cerebral glioma. Instead, combined use of various functional imaging technique such as MRI or PET is considered as an inevitable for clinical use or investigational use. As PET-MR machine is now introduced for several institutes in Germany, the USA and Japan, establishment of precise combination of imaging techniques for the functional study of glioma is mandatory.
      In this review article, the author summarized topics in this field by presenting his own cases or by reviewing published articles. Topics discussed are : 1) Imaging of glioma metabolism imaging with PET and MRS, 2) Imaging of tumor vascular volume and permeability, 3) Usefulness of pharmacological PET for glioma, and 4) Recent imaging topics selected by the author.
      Use of the state-of-the-art functional imaging technique should be the key method to connect the basic and clinical science in the field of glioma treatment. Establishment of the optimum combination of various technique is mandatory for progress of glioma treatment.
    Download PDF (4650K)
  • Yasuo Iwadate, Kazumasa Fukuda, Tomoo Matsutani, Naokatsu Saeki
    2014 Volume 23 Issue 7 Pages 569-580
    Published: 2014
    Released: July 25, 2014
      Gliomas arising in the brain parenchyma infiltrate into the surrounding brain to breakdown the established complex neuron-glia network. Mounting evidences suggests that the adult brain parenchyma innately restricts axonal regrowth and cellular infiltrations including those of glioma cells mainly by inhibitory molecules in CNS myelin as well as the proteoglycans associated with astrocytes. These mechanisms have been shown to be a major hurdle for successful axon regeneration at the time of brain injury. However, these innate inhibitory mechanisms may be injured by radiation therapy, which could compromise patients' survival periods as well as lead to long-term cognitive impairment. Herein, we review the molecular basis of the innate inhibitory mechanisms of the neuron-glia network and discuss its clinical implications. Greater insight into the interaction of glioma cells and the surrounding brain parenchyma is crucial for developing new therapies for theating these devastating tumors while still preserving the complex neuron-glia network.
    Download PDF (2036K)
  • Yuichiro Fukumoto, Nobuhito Morota, Yoko Shioda, Tetsuya Mori
    2014 Volume 23 Issue 7 Pages 581-588
    Published: 2014
    Released: July 25, 2014
      Langerhans cell histiocytosis (LCH) is a relatively rare disease that can result in late complications in the central nervous system (CNS). Recent advancement in clinical findings and chemotherapies has changed the treatment algorithm for LCH.
      We retrospectively reviewed the clinical course and outcome of patients with LCH treated at the National Center for Child Health and Development from March 2005 to September 2010. There were 14 patients (8 boys, 6 girls ; median age : 5 years 4 months, range : 6 months to 14 years 2 months) who underwent neurosurgical treatments. Subclassification of the LCH type was single-system single-site (SS-s : n=8), single-system multisite (SS-m : n=2), and multisystem (MS : n=4).
      The most common initial symptom was a painful, slow-growing skull mass. Preceding head trauma at the site of LCH was reported in 3 patients. Except for the first patient who underwent total resection, the remaining 13 patients received chemotherapy. Complete remission was obtained in 11 patients while reactivation developed in 2 patients during the follow-up period (mean duration : 48 months).
      Since LCH can develop in multiple systems and late reactivation is common, systemic examination and treatment seems indispensable. The prevention of late CNS complications is also important for long-term prognosis. Our limited experience manifested the possible risks of surgical treatment alone. Nearly half of the patients had involvement in multiple regions and organs, and despite chemotherapy, LCH was reactivated in 2 of them. Long-term follow-up in collaboration with pediatric oncologists is strongly recommended.
    Download PDF (1563K)
  • Kojiro Wada, Naoki Otani, Hideo Osada, Arata Tomiyama, Satoshi Tomura, ...
    2014 Volume 23 Issue 7 Pages 589-595
    Published: 2014
    Released: July 25, 2014
      Cotton surgical patties are essential to control vessel bleeding. However, conventional cotton surgical patties tend to adhere to vessels through capillary action, especially when used in combination with hemostats. Consequently, after the bleeding is controlled, rebleeding often tends to occur after removal of the adhered cotton patty. Polyester film-coated non-woven fabric has replaced conventional gauze for the protection of burn wounds, because this material does not tend to adhere to the wound but retains the same capacity to absorb fluid discharges from the wound. We describe our manufacture of a new type of polyurethane-coated surgical patty, which was evaluated for its bleeding control when used in conjunction with a hemostat and for undesirable vessel adherence.
      Our newly developed surgical patty is made of 100% cotton, with only the contact surface coated with polyurethane. The coated side contains many holes, so aspiration through the surgical patty is possible from both sides. For our evaluation, we used a surgical patty with or without polyurethane coating together with a gelatinous sponge for bleeding control in the sagittal sinus, with fibrin glue-soaked oxidized cellulose cotton for bleeding control in the cavernous sinus, and with a collagen sheet for bleeding control in brain capillary vessels, in 5 patients for each use. We found that the newly developed surgical patty could be removed from the hemostat and vessels without difficulty and rebleeding was not observed. The new polyurethane-coated surgical patties appear to be more effective for vessel bleeding control when used with several types of hemostats in different applications and at different locations as compared to conventional non-coated surgical patties.
    Download PDF (1967K)
  • Hiroaki Murayama, Tohru Horikoshi, Nobuo Senbokuya, Takashi Yagi, Hiro ...
    2014 Volume 23 Issue 7 Pages 597-603
    Published: 2014
    Released: July 25, 2014
      We report a rare case of spontaneous intracranial hypotension accompanying thrombosis of the cerebral cortical veins and the superior sagittal sinus. A 43-year-old female who had suffered from orthostatic headache was admitted to a local hospital under the diagnosis of intracranial hypotension. At 15 days after onset, the headache had worsened and was combined with epileptic seizures, in spite of the patient being restricted to bed rest and the administration of intravenous hydration. Magnetic resonance (MR) imaging and cerebral angiography taken in our institute on day 22 revealed a thrombosis of the superior sagittal sinus and the adjacent cortical veins. Radionuclide cisternography demonstrated a cerebrospinal fluid leak at the lower thoracic spine. After anticoagulation therapy was administered followed by an epidural blood patch, the patient recovered with no neurological deficits. Intracranial hypotension accompanying cerebral venous thrombosis is very rare ; however, we should be aware of this complication and alert to its possible manifestation, especially when patients show changes in their headache features and symptoms even when observing a regime of strict bed rest.
    Download PDF (1172K)