Procarbazine and CCNU Chemotherapy for Recurrent Glioblastoma with MGMT Promoter Methylation.

BACKGROUND: While procarbazine, CCNU (lomustine), and vincristine (PCV) has been an alternative chemotherapy option for malignant gliomas, it is worth investigating whether the combination of only procarbazine and CCNU is comparable because vincristine adds toxicity with uncertain benefit. The purpose of this study was to evaluate the feasibility of procarbazine and CCNU chemotherapy for recurrent glioblastoma multiforme (GBM) with O6-methylguanine-DNA-methyltransferase (MGMT) promoter methylation. METHODS: Eight patients with recurrent GBM following concurrent chemoradiotherapy and temozolomide (TMZ) adjuvant therapy were enrolled in this trial; they received no other chemotherapeutic agents or target therapy. They received CCNU (75 mg/m2) on day 1 and procarbazine (60 mg/m2) through days 11 and 24 every 4 weeks. The median cycle of CCNU and procarbazine was 3.5 (range: 2-6). RESULTS: One patient achieved stable disease. The median progression-free survival (PFS) with procarbazine and CCNU chemotherapy was eight weeks (range: 5-73), and the PFS rates were 25% and 12.5% at 16 and 30 weeks, respectively. The median overall survival (OS) from the initial diagnosis to death was 40 months, and the median OS from the administration of procarbazine and CCNU chemotherapy to death was 9.7 months (95% confidence interval: 6.7-12.7). Serious adverse events were found at six visits, and two cases were considered to be grade 3 toxicities. CONCLUSION: The efficacy of procarbazine and CCNU chemotherapy is not satisfactory. This study suggests the need to develop other treatment strategies for recurrent and TMZ-refractory GBM. Trial registry at ClinicalTrials.gov, NCT017337346.

Advanced T and Natural Killer Cell Therapy for Glioblastoma.

Although immunotherapy has been broadly successful in the treatment of hematologic malignancies and a subset of solid tumors, its clinical outcomes for glioblastoma are still inadequate. The results could be due to neuroanatomical structures such as the bloodbrain- barrier, antigenic heterogeneity, and the highly immunosuppressive microenvironment of glioblastomas. The antitumor efficacy of endogenously activated effector cells induced by peptide or dendritic cell vaccines in particular has been insufficient to control tumors. Effector cells, such as T cells and natural killer (NK) cells can be expanded rapidly ex vivo and transferred to patients. The identification of neoantigens derived from tumor-specific mutations is expanding the list of tumor-specific antigens for glioblastoma. Moreover, recent advances in gene-editing technologies enable the effector cells to not only have multiple biological functionalities, such as cytokine production, multiple antigen recognition, and increased cell trafficking, but also relieve the immunosuppressive nature of the glioblastoma microenvironment by blocking immune inhibitory molecules, which together improve their cytotoxicity, persistence, and safety. Allogeneic chimeric antigen receptor (CAR) T cells edited to reduce graft-versushost disease and allorejection, or induced pluripotent stem cell-derived NK cells expressing CARs that use NK-specific signaling domain can be a good candidate for off-the-shelf products of glioblastoma immunotherapy. We here discuss current progress and future directions for T cell and NK cell therapy in glioblastoma.

O6-methylguanine-DNA-methyltransferase promoter methylation assessment by microdissection-assisted methylation-specific PCR and high resolution melting analysis in patients with glioblastomas.

We have determined O(6)-methylguanine-DNA-methyltransferase (MGMT) promoter methylation status by methylation-specific polymerase chain reaction (MSP) in 22 paraffin-embedded specimens of glioblastoma multiforme. A MGMT methylation-specific high resolution melting (HRM) assay was performed to compare the methylation levels of the tumorous and non-tumorous portions of each sample, which were selectively collected using a microdissection technique. MGMT methylation was detected in 10 patients using MSP, while 8 patients had both methylated and unmethylated MGMT promoters. HRM assays showed that there was no difference in the level of methylation between tumorous and non-tumorous portions of each sample. In patients with MSP-positive tumors, the overall survival (median, 22 months) was longer as compared to those with MSP-negative tumors (median, 14 months). A correlation between the methylation status of the MGMT promoter and MGMT protein expression was observed in 12 samples. This study demonstrates that MGMT methylation is not restricted to glioblastoma cells. Additionally, methylation-specific HRM is a feasible approach that can be readily applied to the methylation analysis of MGMT. A further study will be needed to determine the dynamic change of MGMT methylation in the tumor environment.

Animal models for vaccine therapy.

Animal models are important for defining paradigms of tumor immunology and for evaluating therapeutic efficacy of immunotherapy. Many animal models have been used for evaluating in vivo characteristics of malignant gliomas and their responses to therapy. No animal model, however, is perfect because malignant glioma has a very heterogeneous biological behavior. There are so many parallels between mouse and human immunology, but there are significant discrepancies in immune system. Animal models for vaccine therapy can be classified as transplantable tumor models and models of spontaneous tumor in genetically engineered animals. Although transplantable tumor models have been used to test immunotherapeutic efficacy and remain a mainstay in study of brain tumor immunology, a lot of tumor vaccines that look promising in experimental animals have turned out to be ineffective clinically. Recent advances of laboratory techniques and understanding of genetic and molecular characteristics of gliomas allows for animal models of gliomas with similar biologic characteristics. Well-designed glioma models that accurately reflect the biology, pathology and clinical behaviors of human gliomas can provide more useful preclinical informations to predict clinical efficacy of novel immunotherapies and cancer vaccines.

Utilizing a Novel Pituitary Retractor for Early Descent of the Diaphragma Sellae during Endoscopic Transsphenoidal Pituitary Surgery.

OBJECTIVE: Early descent of the diaphragm sellae (DS) during endoscopic endonasal transsphenoidal surgery (EETS) for pituitary macroadenoma surgery is occasionally a troublesome event by blocking the surgical field. Here we introduce an alternative technique with the new pituitary retractor and present our clinical experiences. METHODS: We designed a simple and rigid pituitary retractor with the least space occupation in the nasal cavity to be compatible in EETS. The pituitary retractor was held by external holder system to support the herniated DS stably. We retrospectively reviewed a clinical 22 cases of pituitary macroadenomas underwent EETS using the pituitary retractor. RESULTS: The pituitary retractor stably pushed up the herniated DS in all cases, and the surgeon proceeded the procedure with bimanual maneuver. The pituitary retractor was helpful to remove tumors around the medial cavernous sinus and behind the DS in 16 and seven cases, respectively. In four cases, the meticulous hemostasis was completed with the direct visualization by the DS elevation with this retractor. Gross total tumor resection was performed in 20/22 patients (91%). The impaired visual function and hypopituitarism were improved in 18/20 (90%) and 7/14 (50%) patients after surgery, respectively. There was no complication related with the pituitary retractor. CONCLUSION: During EETS for pituitary macroadenomas, the novel pituitary retractor reported in this study is a very useful technique when the herniated DS block the surgical field and bimanual maneuver. This pituitary retractor can help to result in the excellent surgical outcomes with minimal morbidity.

Evaluation of 3-Dimensional Exoscopes in Brain Tumor Surgery.

OBJECTIVE: Though the operating microscope (OM) has been the standard optical system in neurosurgery, a new technology called three-dimensional (3D) exoscope has emerged as an alternative. Herein, two types of 3D exoscopes for brain tumor surgery are presented. In addition, the advantages and limitations compared with the OM are discussed. METHODS: In the present study, 3D exoscope VOMS-100 or VITOM 3D was used in 11 patients with brain tumor who underwent surgical resection; the Kinevo 900 OM was used only in emergency. After completion of all surgeries, the participants were surveyed with a questionnaire regarding video image quality on the display monitor, handling of equipment, ergonomics, educational usefulness, 3D glasses, and expectation as a substitute for the OM. RESULTS: Among 11 patients, nine patients underwent neurosurgical resection with only 3D exoscope; however, two patients required additional aid with the OM due to difficulty in hemostasis. Regarding video image quality, VITOM 3D was mostly equivalent to the OM, but VOMS-100 was not. However, both 3D exoscopes showed advantages in accessibility of instruments in the surgical field and occupied less space in the operating theater. Differences in ergonomics and educational usefulness between the exoscopes were not reported. Respondents did not experience discomfort in wearing 3D glasses and thought the exoscopes could be currently, and in the future, used as a substitute for the OM. CONCLUSION: Although many neurosurgeons are not familiar with 3D exoscopes, they have advantages compared with the OM and similar image quality. Exoscopes could be a substitute for OM in the future if some limitations are overcome.

High-dose methotrexate monotherapy for newly diagnosed primary central nervous system lymphoma: 15-year multicenter experience.

AIM: Primary central nervous system lymphoma (PCNSL) is rare disease and shows poor prognosis although methotrexate-based chemotherapy is used. Here, we present our experiences with high-dose methotrexate (HD-MTX) monotherapy for immunocompetent patients with PCNSL at three institutions and investigate factors related to survival. METHODS: PCNSL patients, who were histologically confirmed with diffuse large B cells and treated with HD-MTX monotherapy from 2001 to 2016, were retrospectively reviewed. Patients underwent induction chemotherapy with 8 g/m2 of MTX every 10 days (maximum three cycles). Maintenance chemotherapy of 3.5 g/m2 of MTX (maximum six cycles) was selectively performed depending on the response to induction chemotherapy. RESULTS: A total of 67 patients were included. Although seven patients discontinued induction chemotherapy because of MTX toxicity, 40 (59.7%) patients showed a complete response (CR) to induction chemotherapy. Twenty-six (38.8%) and three (4.5%) patients showed a CR and partial response, respectively, after maintenance chemotherapy. Forty-one patients with recurrence or progression following HD-MTX underwent second-line treatment. Progression-free survival rates were 43% and 24% at 1 and 2 years, respectively. The median overall survival was 40.3 months. In a multivariate analysis, a radiological CR to induction chemotherapy was a significant factor related to prolonged progression-free survival and overall survival (P < 0.05). CONCLUSION: MTX-monotherapy is tolerable in terms of adverse effects and still considered as a treatment option in patients with PCNSL. However, an additional therapeutic option should be prepared for non-CR responders to induction chemotherapy.

The Korean Society for Neuro-Oncology (KSNO) Guideline for WHO Grade III Cerebral Gliomas in Adults: Version 2019.01.

BACKGROUND: There was no practical guideline for the management of patients with central nervous system tumor in Korea in the past. Thus, the Korean Society for Neuro-Oncology (KSNO), a multidisciplinary academic society, developed the guideline for glioblastoma successfully and published it in Brain Tumor Research and Treatment, the official journal of KSNO, in April 2019. Recently, the KSNO guideline for World Health Organization (WHO) grade III cerebral glioma in adults has been established. METHODS: The Working Group was composed of 35 multidisciplinary medical experts in Korea. References were identified by searches in PubMed, MEDLINE, EMBASE, and Cochrane CENTRAL databases using specific and sensitive keywords as well as combinations of keywords. Scope of the disease was confined to cerebral anaplastic astrocytoma and oligodendroglioma in adults. RESULTS: Whenever radiological feature suggests high grade glioma, maximal safe resection if feasible is globally recommended. After molecular and histological examinations, patients with anaplastic astrocytoma, isocitrate dehydrogenase (IDH)-mutant should be primary treated by standard brain radiotherapy and adjuvant temozolomide chemotherapy whereas those with anaplastic astrocytoma, NOS, and anaplastic astrocytoma, IDH-wildtype should be treated following the protocol for glioblastomas. In terms of anaplastic oligodendroglioma, IDH-mutant and 1p19q-codeletion, and anaplastic oligodendroglioma, NOS should be primary treated by standard brain radiotherapy and neoadjuvant or adjuvant PCV (procarbazine, lomustine, and vincristine) combination chemotherapy. CONCLUSION: The KSNO's guideline recommends that WHO grade III cerebral glioma of adults should be treated by maximal safe resection if feasible, followed by radiotherapy and/or chemotherapy according to molecular and histological features of tumors.

The Korean Society for Neuro-Oncology (KSNO) Guideline for WHO Grade II Cerebral Gliomas in Adults: Version 2019.01.

BACKGROUND: There was no practical guideline for the management of patients with central nervous system tumor in Korea for many years. Thus, the Korean Society for Neuro-Oncology (KSNO), a multidisciplinary academic society, has developed the guideline for glioblastoma. Subsequently, the KSNO guideline for World Health Organization (WHO) grade II cerebral glioma in adults is established. METHODS: The Working Group was composed of 35 multidisciplinary medical experts in Korea. References were identified by searching PubMed, MEDLINE, EMBASE, and Cochrane CENTRAL databases using specific and sensitive keywords as well as combinations of keywords regarding diffuse astrocytoma and oligodendroglioma of brain in adults. RESULTS: Whenever radiological feature suggests lower grade glioma, the maximal safe resection if feasible is recommended globally. After molecular and histological examinations, patients with diffuse astrocytoma, isocitrate dehydrogenase (IDH)-wildtype without molecular feature of glioblastoma should be primarily treated by standard brain radiotherapy and adjuvant temozolomide chemotherapy (Level III) while those with molecular feature of glioblastoma should be treated following the protocol for glioblastomas. In terms of patients with diffuse astrocytoma, IDH-mutant and oligodendroglioma (IDH-mutant and 1p19q codeletion), standard brain radiotherapy and adjuvant PCV (procarbazine+lomustine+vincristine) combination chemotherapy should be considered primarily for the high-risk group while observation with regular follow up should be considered for the low-risk group. CONCLUSION: The KSNO's guideline recommends that WHO grade II gliomas should be treated by maximal safe resection, if feasible, followed by radiotherapy and/or chemotherapy according to molecular and histological features of tumors and clinical characteristics of patients.

The Korean Society for Neuro-Oncology (KSNO) Guideline for Glioblastomas: Version 2018.01.

BACKGROUND: There has been no practical guidelines for the management of patients with central nervous system (CNS) tumors in Korea for many years. Thus, the Korean Society for Neuro-Oncology (KSNO), a multidisciplinary academic society, started to prepare guidelines for CNS tumors from February 2018. METHODS: The Working Group was composed of 35 multidisciplinary medical experts in Korea. References were identified through searches of PubMed, MEDLINE, EMBASE, and Cochrane CENTRAL using specific and sensitive keywords as well as combinations of keywords. RESULTS: First, the maximal safe resection if feasible is recommended. After the diagnosis of a glioblastoma with neurosurgical intervention, patients aged ≤70 years with good performance should be treated by concurrent chemoradiotherapy with temozolomide followed by adjuvant temozolomide chemotherapy (Stupp's protocol) or standard brain radiotherapy alone. However, those with poor performance should be treated by hypofractionated brain radiotherapy (preferred)±concurrent or adjuvant temozolomide, temozolomide alone (Level III), or supportive treatment. Alternatively, patients aged >70 years with good performance should be treated by hypofractionated brain radiotherapy+concurrent and adjuvant temozolomide or Stupp's protocol or hypofractionated brain radiotherapy alone, while those with poor performance should be treated by hypofractionated brain radiotherapy alone or temozolomide chemotherapy if the patient has methylated MGMT gene promoter (Level III), or supportive treatment. CONCLUSION: The KSNO's guideline recommends that glioblastomas should be treated by maximal safe resection, if feasible, followed by radiotherapy and/or chemotherapy according to the individual comprehensive condition of the patient.

Memantine Induces NMDAR1-Mediated Autophagic Cell Death in Malignant Glioma Cells.

OBJECTIVE: Autophagy is one of the key responses of cells to programmed cell death. Memantine, an approved anti-dementia drug, has an antiproliferative effect on cancer cells but the mechanism is poorly understood. The aim of the present study was to test the possibility of induction of autophagic cell death by memantine in glioma cell lines. METHODS: Glioma cell lines (T-98 G and U-251 MG) were used for this study. RESULTS: The antiproliferative effect of memantine was shown on T-98 G cells, which expressed N-methyl-D-aspartate 1 receptor (NMDAR1). Memantine increased the autophagic-related proteins as the conversion ratio of light chain protein 3-II (LC3-II)-/LC3-I and the expression of beclin-1. Memantine also increased formation of autophagic vacuoles observed under a transmission electron microscope. Transfection of small interfering RNA (siRNA) to knock down NMDAR1 in the glioma cells induced resistance to memantine and decreased the LC3-II/LC3-I ratio in T-98 G cells. CONCLUSION: Our study demonstrates that in glioma cells, memantine inhibits proliferation and induces autophagy mediated by NMDAR1.

Concurrent Chemoradiotherapy with Temozolomide Followed by Adjuvant Temozolomide for Newly Diagnosed Glioblastoma Patients: A Retrospective Multicenter Observation Study in Korea.

PURPOSE: The purpose of this study was to investigate the feasibility and survival benefits of combined treatment with radiotherapy and adjuvant temozolomide (TMZ) in a Korean sample. MATERIALS AND METHODS: A total of 750 Korean patients with histologically confirmed glioblastoma multiforme, who received concurrent chemoradiotherapy with TMZ (CCRT) and adjuvant TMZ from January 2006 until June 2011, were analyzed retrospectively. RESULTS: After the first operation, a gross total resection (GTR), subtotal resection (STR), partial resection (PR), biopsy alone were achieved in 388 (51.7%), 159 (21.2%), 96 (12.8%), and 107 (14.3%) patients, respectively. The methylation status of O6-methylguanine-DNA methyltransferase (MGMT) was reviewed retrospectively in 217 patients. The median follow-up period was 16.3 months and the median overall survival (OS) was 17.5 months. The actuarial survival rates at the 1-, 3-, and 5-year OS were 72.1%, 21.0%, and 9.0%, respectively. The median progression-free survival (PFS) was 10.1 months, and the actuarial PFS at 1-, 3-, and 5-year PFS were 42.2%, 13.0%, and 7.8%, respectively. The patients who received GTR showed a significantly longer OS and PFS than those who received STR, PR, or biopsy alone, regardless of the methylation status of the MGMT promoter. Patients with a methylated MGMT promoter also showed a significantly longer OS and PFS than those with an unmethylated MGMT promoter. Patients who received more than six cycles of adjuvant TMZ had a longer OS and PFS than those who received six or fewer cycles. Hematologic toxicity of grade 3 or 4 was observed in 8.4% of patients during the CCRT period and in 10.2% during the adjuvant TMZ period. CONCLUSION: Patients treated with CCRT followed by adjuvant TMZ had more favorable survival rates and tolerable toxicity than those who did not undergo this treatment.

Unusual Radiologic Finding of Intracranial Inflammatory Myofibroblastic Tumor Presenting a Cyst with Mural Nodule.

An intracranial cyst tumor with a mural nodule can be representative of some types of brain tumors, but is a rare presentation of intracranial inflammatory myofibroblastic tumor (IMT). Herein, we report the case of an intracranial IMT in a 48-year-old woman presenting with the extremely unusual radiologic findings of a cyst with a mural nodule.

A new hope in immunotherapy for malignant gliomas: adoptive T cell transfer therapy.

Immunotherapy emerged as a promising therapeutic approach to highly incurable malignant gliomas due to tumor-specific cytotoxicity, minimal side effect, and a durable antitumor effect by memory T cells. But, antitumor activities of endogenously activated T cells induced by immunotherapy such as vaccination are not sufficient to control tumors because tumor-specific antigens may be self-antigens and tumors have immune evasion mechanisms to avoid immune surveillance system of host. Although recent clinical results from vaccine strategy for malignant gliomas are encouraging, these trials have some limitations, particularly their failure to expand tumor antigen-specific T cells reproducibly and effectively. An alternative strategy to overcome these limitations is adoptive T cell transfer therapy, in which tumor-specific T cells are expanded ex vivo rapidly and then transferred to patients. Moreover, enhanced biologic functions of T cells generated by genetic engineering and modified immunosuppressive microenvironment of host by homeostatic T cell expansion and/or elimination of immunosuppressive cells and molecules can induce more potent antitumor T cell responses and make this strategy hold promise in promoting a patient response for malignant glioma treatment. Here we will review the past and current progresses and discuss a new hope in adoptive T cell therapy for malignant gliomas.

Long-term incidence and predicting factors of cranioplasty infection after decompressive craniectomy.

OBJECTIVE: The predictors of cranioplasty infection after decompressive craniectomy have not yet been fully characterized. The objective of the current study was to compare the long-term incidences of surgical site infection according to the graft material and cranioplasty timing after craniectomy, and to determine the associated factors of cranioplasty infection. METHODS: A retrospective cohort study was conducted to assess graft infection in patients who underwent cranioplasty after decompressive craniectomy between 2001 and 2011 at a single-center. From a total of 197 eligible patients, 131 patients undergoing 134 cranioplasties were assessed for event-free survival according to graft material and cranioplasty timing after craniectomy. Kaplan-Meier survival analysis and Cox regression methods were employed, with cranioplasty infection identified as the primary outcome. Secondary outcomes were also evaluated, including autogenous bone resorption, epidural hematoma, subdural hematoma and brain contusion. RESULTS: The median follow-up duration was 454 days (range 10 to 3900 days), during which 14 (10.7%) patients suffered cranioplasty infection. There was no significant difference between the two groups for event-free survival rate for cranioplasty infection with either a cryopreserved or artificial bone graft (p=0.074). Intergroup differences according to cranioplasty time after craniectomy were also not observed (p=0.083). Poor neurologic outcome at cranioplasty significantly affected the development of cranioplasty infection (hazard ratio 5.203, 95% CI 1.075 to 25.193, p=0.04). CONCLUSION: Neurologic status may influence cranioplasty infection after decompressive craniectomy. A further prospective study about predictors of cranioplasty infection including graft material and cranioplasty timing is necessary.

Immunological factors relating to the antitumor effect of temozolomide chemoimmunotherapy in a murine glioma model.

In this study, we investigated the potential of combined treatment with temozolomide (TMZ) chemotherapy and tumor antigen-pulsed dendritic cells (DCs) and the underlying immunological factors of TMZ chemoimmunotherapy with an intracranial GL26 glioma animal model. The combined treatment enhanced the tumor-specific immune responses and prolonged the survival more effectively than either single therapy in GL26 tumor-bearing animals. Apoptosis was induced in the tumors of the animals by the treatment with TMZ. Calreticulin (CRT) surface exposure was detected by immunofluorescence staining of TMZ-treated GL26 cells. TMZ chemotherapy increased tumor antigen cross-priming from tumor cells, leading to cross-priming of tumor antigen-specific CD4(+) T cells and CD8(+) T cells. This chemotherapy appeared to suppress the frequency of CD4(+) CD25(+) regulatory T cells (Treg). Moreover, this combined therapy resulted in an increase in the tumor infiltration of CD4(+) and CD8(+) T cells. Collectively, the findings of this study provide evidence that the combination of TMZ chemotherapy and treatment with DC-based vaccines leads to the enhancement of antitumor immunity through increased tumor-specific immune responses via the cross-priming of apoptotic tumor cell death mediated by CRT exposure and, in part, the suppression of Treg. Therefore, CRT exposure, regulatory T cells, and cross-priming by TMZ chemotherapy may be immunological factors related to the enhancement of the antitumor effects of chemoimmunotherapy in an experimental brain tumor model.

Cervical disc herniation producing acute brown-sequard syndrome.

Brown-Sequard syndrome may be the result of penetrating injury to the spine, but many other etiologies have been described. This syndrome is most commonly seen with spinal trauma and extramedullary spinal neoplasm. A herniated cervical disc has been rarely reported as a cause of this syndrome. We present a case of a 28-year-old male patient diagnosed as large C3-C4 disc herniation with spinal cord compression. He presented with left hemiparesis and diminished sensation to pain and temperature in the right side below the C4 dermatome. Microdiscectomy and anterior cervical fusion with carbon fiber cage containing a core of granulated coralline hydroxyapatite was performed. After the surgery, rapid improvement of the neurologic deficits was noticed. We present a case of cervical disc herniation producing acute Brown-Sequard syndrome with review of pertinent literature.

Inhibitory Effect of IFN-beta, on the Antitumor Activity of Celecoxib in U87 Glioma Model.

OBJECTIVE: Interferon-beta, (IFN-beta) has been used in the treatment of cancers. Inhibition of the enzyme cyclooxygenase (COX) with celecoxib had a significantly suppressive effect on tumor growth, angiogenesis, and metastasis in a variety of tumors. The aim of this study was to elucidate the antiglioma effect of combined treatment with IFN-beta and celecoxib in U87 glioma model. METHODS: The in vitro effects of IFN-beta (50-1,000 IU/mL) and celecoxib (50-250 microM) alone or combination of both on the proliferation and apoptosis of U87 cells were tested using MTT assay, FACS analysis and DNA condensation. To determine the in vivo effect, nude mice bearing intracerebral U87 xenograft inoculation were treated with IFN-beta intraperitoneally (2x10(5) IU/day for 15 days), celecoxib orally (5, 10 mg/kg) or their combination. RESULTS: IFN-beta or celecoxib showed an inhibitory effect on the proliferation of U87 cells. When U87 cells were treated with IFN-beta and celecoxib combination, it seemed that IFN-beta interrupted the antiproliferative and apoptotic activity of celecoxib. No additive effect was observed on the survival of the tumor bearing mice by the combination of IFN-beta and celecoxib. CONCLUSION: These results suggest that IFN-beta seems to inhibit the antiglioma effect of celecoxib, therefore combination of IFN-beta and celecoxib may be undesirable in the treatment of glioma.

Surgical treatments for cervical spondylotic myelopathy associated with athetoid cerebral palsy.

OBJECTIVE: To evaluate the clinical characteristics and surgical outcomes of the patients with cervical spondylotic myelopathy associated with athetoid cerebral palsy. METHODS: The authors reviewed the clinical and neurodiagnostic findings, surgical managements and outcomes in six consecutive patients with cervical spondylotic myelopathy associated with athetoid cerebral palsy who had been treated with surgical decompression and fusion procedures between January 1999 and December 2005. The mean age of the 6 patients (four women and two men) at the time of surgery was 42.8 years (range, 31-55 years). The mean follow-up period was 56.5 months (range, 17-112 months). The neurological outcome was evaluated before and after operations (immediately, 6 months after and final follow-up) using grading systems of the walking ability, brachialgia and deltoid power. RESULTS: At immediate postoperative period, after 6 months, and at final follow-up, all patients showed apparent clinical improvements in walking ability, upper extremity pain and deltoid muscle strength. Late neurological deterioration was not seen during follow-up periods. There were no serious complications related to surgery. CONCLUSION: Surgical decompression and stabilization in patients with cervical spondylotic myelopathy associated with athetoid cerebral palsy have been challenging procedure up to now. Our results indicate that early diagnosis and appropriate surgical procedure can effectively improve the clinical symptoms and neurological function in patients with cervical spondylotic myelopathy and athetoid cerebral palsy, even in those with severe involuntary movements.

Sacral insufficiency fracture, usually overlooked cause of lumbosacral pain.

Sacral insufficiency fractures are usually known to develop in elderly patients with osteoporosis without definite trauma history. It is difficult to diagnose the sacral insufficiency fracture at an early stage because lower lumbar diseases, concurrently or not, may also be presented with similar symptoms and signs. We report a rare case of sacral insufficiency fracture who was not diagnosed initially but, instead, showed progressively worsening of clinical symptoms and radiological findings after decompression surgery for upper level lumbar stenosis.