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1.
No Shinkei Geka ; 48(7): 587-594, 2020 Jul.
Article in Japanese | MEDLINE | ID: mdl-32694227

ABSTRACT

BACKGROUND: Growing teratoma syndrome(GTS)is the progression of a mature teratoma during or following radiochemotherapy for germ cell tumors. We report two surgical cases of GTS. CASE 1: A 24-day-old new-born presented with vomiting and head enlargement. Blood alfa-feto protein(AFP)and beta-human chorionic gonadotropin(ß-hCG)were within or at the upper limits of the normal ranges. Magnetic Resonance Imaging(MRI)demonstrated a large mass in the posterior fossa causing the severe hydrocephalus. Tumor removal was immediately performed. Histological diagnosis given was immature teratoma. While chemotherapy effectively reduced the level of tumor makers, multiple recurrence was noticed on MRI 70 days after the surgery. GTS was suspected and total removal was performed. Histological examination revealed a mature teratoma. The patient is growing normally thereafter, 2.5 years after the onset. CASE 2: A 16-year-old male presented with binasal hemianopsia. Blood AFP and ß-hCG were within or at the upper limits of the normal ranges. MRI demonstrated an intrasellar mass protruding upward. Tumor removal was performed and histological diagnosis given was mixed germ cell tumor. While radiochemotherapy effectively normalized the tumor makers, recurrence was noticed on MRI 190 days after the surgery. Total removal was performed with the diagnosis of GTS. Histological examination revealed a mature teratoma. The patient lives a normal school life thereafter as followed up after a year after the onset. CONCLUSION: It is important to diagnose and perform the surgery early enough to enable total removal of the mass presenting as GTS because total surgical removal is the only treatment for GTS.


Subject(s)
Neoplasms, Germ Cell and Embryonal , Teratoma , Adolescent , Humans , Magnetic Resonance Imaging , Male , Neoplasm Recurrence, Local , Syndrome
2.
J Neurooncol ; 134(1): 83-88, 2017 Aug.
Article in English | MEDLINE | ID: mdl-28534151

ABSTRACT

Carmustine wafers (CW) were approved in Japan for newly diagnosed and recurrent malignant gliomas during 2013. The ventricle is often opened during surgery to achieve maximum resection. While not generally recommended in such situations, CW might be safely achieved by occluding an opened ventricle using gelform or collagen sheets. However, whether CW implantation actually confers a survival benefit for patients who undergo surgery with an open ventricle to treat glioblastoma remains unclear. Clinical, imaging, and survival data were collected in this multicenter retrospective study of 122 consecutive patients with newly diagnosed glioblastoma to determine adverse events and efficacy. Overall, 54 adverse events of all grades developed in 35 (28.6%) patients, with the most common being new seizures (16%). Adverse events did not significantly differ between patients with opened and closed ventricles during surgery. The 10- and 21.7-month, median, progression-free (PFS) and overall survival (OS), respectively did not significantly differ according to resection rates. However, median PFS and OS were significantly longer among patients with closed, than open ventricles (12.8 vs. 7.4 months; p = 0.0039 and 26.9 vs. 18.6 months; p = 0.011, respectively). Implanting CW into the resection cavity during concomitant radiochemotherapy with temozolomide seems to yield better survival rates without increased adverse events. Occlusion of the ventricular opening during surgery might be safe for CW implantation, but less so for treating patients with newly diagnosed glioblastoma.


Subject(s)
Brain Neoplasms , Cerebral Ventricles/surgery , Glioblastoma , Adult , Aged , Aged, 80 and over , Antineoplastic Agents , Brain Neoplasms/diagnostic imaging , Brain Neoplasms/drug therapy , Brain Neoplasms/mortality , Brain Neoplasms/surgery , Carmustine , Chemoradiotherapy , Disease-Free Survival , Female , Glioblastoma/diagnostic imaging , Glioblastoma/drug therapy , Glioblastoma/mortality , Glioblastoma/surgery , Humans , Karnofsky Performance Status , Magnetic Resonance Imaging , Male , Middle Aged , Retrospective Studies , Treatment Outcome , Young Adult
3.
J Stroke Cerebrovasc Dis ; 25(11): e212-e213, 2016 Nov.
Article in English | MEDLINE | ID: mdl-27671095

ABSTRACT

The authors describe a case of a basilar trunk aneurysm with long-term follow-up after successful bypass and proximal occlusion. A 64-year-old woman had a giant aneurysm of the basilar trunk and underwent external carotid artery-to-posterior cerebral artery vein graft bypass surgery and proximal clipping of the basilar artery, which was followed by low-dose aspirin (100 mg/d) treatment. No ischemic symptoms and lesions developed and the thrombosed aneurysm was stable during 11 years of follow-up. An extracranial-intracranial high flow bypass combined with immediate proximal occlusion and aspirin administration may be an acceptable treatment option for patients with giant posterior circulation aneurysms.


Subject(s)
Basilar Artery/surgery , Carotid Artery, External/surgery , Intracranial Aneurysm/surgery , Posterior Cerebral Artery/surgery , Saphenous Vein/transplantation , Vascular Grafting/methods , Aspirin/administration & dosage , Basilar Artery/diagnostic imaging , Basilar Artery/physiopathology , Carotid Artery, External/diagnostic imaging , Carotid Artery, External/physiopathology , Cerebral Angiography/methods , Computed Tomography Angiography , Diffusion Magnetic Resonance Imaging , Female , Fibrinolytic Agents/administration & dosage , Humans , Intracranial Aneurysm/diagnostic imaging , Intracranial Aneurysm/physiopathology , Middle Aged , Posterior Cerebral Artery/diagnostic imaging , Posterior Cerebral Artery/physiopathology , Time Factors , Treatment Outcome , Vascular Patency
4.
J Neurooncol ; 116(2): 299-306, 2014 Jan.
Article in English | MEDLINE | ID: mdl-24173683

ABSTRACT

Age is one of the most important prognostic factors in glioblastoma patients, but no standard treatment has been established for elderly patients with this condition. We therefore conducted a retrospective cohort study to evaluate treatment regimens and outcomes in elderly glioblastoma patients. The study population consisted of 79 glioblastoma patients aged ≥ 76 years (median age 78.0 years; 34 men and 45 women). The median preoperative Karnofsky performance status (KPS) score was 60. Surgical procedures were classified as biopsy (31 patients, 39.2 %), <95 % resection of the tumor (21 patients, 26.9 %), and ≥ 95 % resection of the tumor (26 patients, 33.3 %). Sixty-seven patients (81.0 %) received radiotherapy and 45 patients (57.0 %) received chemotherapy. The median overall progression-free survival time was 6.8 months, and the median overall survival time was 9.8 months. Patients aged ≥ 78 years were significantly less likely to receive radiotherapy (p = 0.004). Patients with a postoperative KPS score of ≥ 60 were significantly more likely to receive maintenance chemotherapy (p = 0.008). Multivariate analyses identified two independent prognostic factors: postoperative KPS score ≥ 60 (hazard ratio [HR] = 0.531, 95 % confidence interval [CI] 0.315-0.894, p = 0.017) and temozolomide therapy (HR = 0.442, 95 % CI 0.25-0.784, p < 0.001).The findings of this study suggest that postoperative KPS score is an important prognostic factor for glioblastoma patients aged ≥ 76 years, and that these patients may benefit from temozolomide therapy.


Subject(s)
Brain Neoplasms/drug therapy , Brain Neoplasms/surgery , Glioblastoma/drug therapy , Glioblastoma/surgery , Treatment Outcome , Aged , Aged, 80 and over , Antineoplastic Agents , Brain Neoplasms/mortality , Cognition Disorders/diagnosis , Cognition Disorders/etiology , Cohort Studies , Disease-Free Survival , Female , Glioblastoma/mortality , Humans , Magnetic Resonance Imaging , Male , Postoperative Complications , Statistics, Nonparametric , Surveys and Questionnaires , Tomography Scanners, X-Ray Computed
5.
No Shinkei Geka ; 40(7): 643-50, 2012 Jul.
Article in Japanese | MEDLINE | ID: mdl-22728543

ABSTRACT

We reported an extremely rare case of cerebellar hemangioblastoma with marked pleomorphism and reviewed the literature. A 68-year-old male presented with a one-month history of headache and vomiting. Neurological examination revealed right-sided dysmetria and truncal ataxia. Contrast-enhanced T1-weighted MR imaging revealed a heterogeneously enhancing tumor with solid and cystic components in the right cerebellum. The solid portion of the tumor was low intensity on diffusion-weighted imaging and low intensity on susceptibility-weighted imaging. 18F-fluorodeoxyglucose PET showed low uptake in the cerebellar tumor and the whole body examination was negative for malignancy. Vertebral angiogram demonstrated moderate tumor staining and no early filling veins. The patient underwent total removal of the tumor through suboccipital craniotomy. Microscopically, the solid tumor contained a cellular rich component consisting of stromal cells and a markedly pleomorphic component including atypical and multinucleated giant cells. The MIB-1 positive rate was 8.2%, which was slightly higher compared to that of hemangioblastomas. We observed strong staining for inhibin-α, aquaporin 1 and neuron specific enolase (NSE) in the tumor cells. PAX-2, cytokeratin and epithelial membrane antigen (EMA) were completely negative in the tumor cells, whereas the tumor cells demonstrated focal staining for CD10. The histological diagnosis was hemangioblastoma. Follow-up MR images showed no evidence of recurrent tumor 14 months after the resection. The study using a combination of immunohistochemical markers (e.g. inhibin-α, aquaporin 1 and PAX-2) is useful for differential diagnosis of hemangioblastoma from metastatic renal cell carcinoma.


Subject(s)
Biomarkers, Tumor/metabolism , Cerebellar Neoplasms/pathology , Cerebellar Neoplasms/surgery , Hemangioblastoma/pathology , Hemangioblastoma/surgery , Aged , Craniotomy , Humans , Immunohistochemistry , Magnetic Resonance Imaging , Male , Treatment Outcome
8.
Neurol Med Chir (Tokyo) ; 61(7): 404-413, 2021 Jul 15.
Article in English | MEDLINE | ID: mdl-33994449

ABSTRACT

The efficacy of stereotactic radiotherapy (SRT) has been well established for postoperative residual and recurrent nonfunctioning pituitary adenomas (NFPAs). However, the risk of visual impairment due to SRT for lesions adjacent to the optic pathways remains a topic of debate. Herein, we evaluated the long-term clinical outcomes of hypofractionated stereotactic radiotherapy (HFSRT) for perioptic NFPAs. From December 2002 to November 2015, 32 patients (18 males and 14 females; median age 63 years; range, 36-83 years) with residual or recurrent NFPAs abutting or displacing the optic nerve and/or chiasm (ONC) were treated with HFSRT. The median marginal dose was 31.3 Gy (range, 17.2-39.6) in 8 fractions (range, 6-15). Magnetic resonance imaging (MRI) and visual and hormonal examinations were performed before and after HFSRT. The median follow-up period was 99.5 months (range, 9-191). According to MRI findings at the last follow-up, the tumor size had decreased in 28 (88%) of 32 patients, was unchanged in 3 (9%), and had increased in 1 (3%). The successful tumor size control rate was 97%. Visual functions remained unchanged in 19 (60%) out of 32 patients, improved in 11 (34%), and deteriorated in 2 (6%). Two patients had deteriorated visual functions; no complications occurred because of the HFSRT. One patient developed hypopituitarism that required hormone replacement therapy. The result of this long-term follow-up study suggests that HFSRT is safe and effective for the treatment of NFPAs occurring adjacent to the ONC.


Subject(s)
Adenoma , Pituitary Neoplasms , Radiosurgery , Adenoma/diagnostic imaging , Adenoma/radiotherapy , Adenoma/surgery , Female , Follow-Up Studies , Humans , Male , Middle Aged , Pituitary Neoplasms/diagnostic imaging , Pituitary Neoplasms/radiotherapy , Pituitary Neoplasms/surgery , Radiosurgery/adverse effects , Retrospective Studies , Treatment Outcome
9.
Neurosurg Rev ; 33(2): 175-83; discussion 183-4, 2010 Apr.
Article in English | MEDLINE | ID: mdl-20135187

ABSTRACT

Dissemination of glioblastoma was once considered rare but is now increasingly encountered with longer survival of glioblastoma patients. Despite the potential negative impact of dissemination on clinical outcome, however, molecular markers useful for prediction of dissemination risk still remains ill defined. We tested in this study for an association between the expression of stem cell marker CD133 and the risk of dissemination in 26 cases of glioblastoma (16 with dissemination and 10 without dissemination). The protein expression of CD133 was examined by western blot analysis of tumor specimens, and the CD133 expression levels were quantified by densitometry and normalized to beta-actin. The results indicated that CD133 expression levels are significantly higher in glioblastomas with dissemination (mean 10.3, range 0.20-27.8) than in those without (mean 1.18, range 0.07-3.58). The results suggest that CD133 could be a molecular predictor of glioblastoma dissemination, and also give rise to an intriguing idea that CD133-positive cancer stem cells may be implicated in the initiation of disseminated lesions.


Subject(s)
Antigens, CD/metabolism , Biomarkers, Tumor/metabolism , Central Nervous System Neoplasms/diagnosis , Central Nervous System Neoplasms/metabolism , Glioblastoma/diagnosis , Glioblastoma/metabolism , Glycoproteins/metabolism , Magnetic Resonance Imaging , Peptides/metabolism , Stem Cells/metabolism , AC133 Antigen , Adolescent , Adult , Aged , Blotting, Western , Central Nervous System Neoplasms/pathology , Child , Disease Progression , Female , Glioblastoma/pathology , Humans , Male , Middle Aged , Risk Assessment , Survival Rate , Time Factors
10.
Neurol Med Chir (Tokyo) ; 60(11): 543-552, 2020 Nov 15.
Article in English | MEDLINE | ID: mdl-33071274

ABSTRACT

Pleomorphic xanthoastrocytoma (PXA) is a rare glial tumor, however, its histological differentiation from high-grade gliomas is often difficult. Molecular characteristics may contribute to a better diagnostic discrimination. Prognostic factors of PXA are also important but few relevant reports have been published. This study investigated the molecular features and prognostic factors of PXAs. Seven university hospitals participated in this study by providing retrospective clinical data and tumor samples of PXA cases between 1993 and 2014. Tumor samples were analyzed for immunohistochemical (IHC) neuronal and glial markers along with Ki67. The status of the BRAF and TERT promoter (TERTp) mutation was also evaluated using the same samples, followed by feature extraction of PXA and survival analyses. In all, 19 primary cases (17 PXA and 2 anaplastic PXA) were included. IHC examination revealed the stable staining of nestin and the close association of synaptophysin to NFP. Of the PXA cases, 57% had the BRAF mutation and only 7% had the TERTp mutation. On univariate analysis, age (≥60 years), preoperative Karnofsky performance status (KPS) (≤80%), and marked peritumoral edema were significantly associated with progression-free survival (PFS). No independent factor was indicated by the multivariate analysis. In conclusion, PXA was characterized by positive nestin staining and a few TERTp mutations. The neuronal differential marker and BRAF status may help in diagnosis. Patient age, preoperative KPS, and marked perifocal edema were associated with PFS. The present study is limited because of small number of cases and its retrospective nature. Further clinical study is needed.


Subject(s)
Astrocytoma/diagnosis , Astrocytoma/genetics , Brain Neoplasms/diagnosis , Brain Neoplasms/genetics , Adolescent , Adult , Age Factors , Aged , Astrocytoma/mortality , Brain Neoplasms/mortality , Child , Female , Humans , Japan , Male , Middle Aged , Mutation/genetics , Nestin/metabolism , Prognosis , Proto-Oncogene Proteins B-raf/genetics , Retrospective Studies , Risk Factors , Survival Rate , Telomerase/genetics , Young Adult
11.
Neurol Med Chir (Tokyo) ; 48(3): 137-9, 2008 Mar.
Article in English | MEDLINE | ID: mdl-18362462

ABSTRACT

A 57-year-old obese female presented with vagal and hypoglossal nerve pareses, and magnetic resonance imaging revealed Chiari malformation type I. Standard surgical treatment for Chiari malformation type I was successfully performed. However, immediately after the patient was extubated, she developed signs of upper airway obstruction and chest radiography revealed pulmonary edema. Her ventilation was assisted by maintaining positive end-expiratory pressure at 8 cmH2O. Intravenous furosemide and hydrocortisone were administered. Her respiratory status improved 12 hours later, and she was extubated 3 days after the operation. Postextubational course was uneventful, and the patient was discharged 2 weeks after extubation. The initial neurological deficits had mostly disappeared by 10 months after the operation. This unusual case of negative pressure pulmonary edema indicates that obesity and lower cranial nerve paresis are further risk factors for pulmonary edema as a postextubational complication of surgical treatment.


Subject(s)
Arnold-Chiari Malformation/surgery , Decompression, Surgical/adverse effects , Foramen Magnum , Pulmonary Edema/etiology , Female , Humans , Laryngismus/complications , Middle Aged , Obesity/complications
12.
No Shinkei Geka ; 36(8): 709-15, 2008 Aug.
Article in Japanese | MEDLINE | ID: mdl-18700534

ABSTRACT

Gliomatosis cerebri is a diffuse growth pattern of glioma consisting of exceptionally extensive infiltration of at least three cerebral lobes. We report a case of histologically confirmed glioblastoma multiforme in the cerebellar vermis which occurred 9 years after treatment for gliomatosis cerebri. A 33-year-old woman presented to our department for evaluation of visual disturbance. T2-weighted magnetic resonance (MR) imaging revealed hyperintense lesions in the bilateral frontal and parietal lobes. Histological examination of biopsy specimens from the left frontal lobe lesion demonstrated diffuse infiltration of glial neoplastic cells with preservation of the underlying cytoarchitecture, leading to the diagnosis of gliomatosis cerebri. She received 60 Gy hyperfractionated irradiation to the whole brain, and the lesion responded partially. The patient remained stable for 4 years, but T2-weighted MR imaging 5 years after the initial treatment showed enlargement of the hyperintense area. She received nimustine hydrochloride chemotherapy, and again partial response was observed. However. T1-weighted MR imaging after administration of gadolinium-diethylenetriaminepenta-acetic acid detected enhanced lesions in the cerebellar vermis, cerebellar hemisphere, and left posterior limb of the internal capsule 9 years after the initial treatment, although no abnormal findings were observed on initial and follow-up MR imaging. She underwent subtotal removal of the lesion in the cerebellar vermis. The surgical specimens were characterized by dense proliferation of atypical tumor cells with scattered mitosis and endothelial proliferation. The histological diagnosis was glioblastoma multiforme. The patient received gamma knife irradiation for the remnant lesion in the cerebellar vermis, and the lesions in the cerebellar hemisphere and left posterior limb of the internal capsule, and chemotherapy with temozolomide. However, multiple enhanced lesions were detected in the cerebellar vermis 2 months after the start of the temozolomide chemotherapy, and she died 8 months later. This case suggests that glioblastoma multiforme could develop in the long term after initial treatment for gliomatosis cerebri, and in a location separate from the initial lesion.


Subject(s)
Brain Neoplasms/therapy , Cerebellum , Glioblastoma/therapy , Neoplasms, Neuroepithelial/therapy , Neoplasms, Second Primary , Adult , Antineoplastic Agents/therapeutic use , Brain Neoplasms/diagnosis , Combined Modality Therapy , Dose Fractionation, Radiation , Fatal Outcome , Female , Glioblastoma/diagnosis , Humans , Magnetic Resonance Imaging , Neoplasms, Neuroepithelial/diagnosis , Radiosurgery , Time Factors
13.
Int J Cancer ; 121(12): 2637-45, 2007 Dec 15.
Article in English | MEDLINE | ID: mdl-17708555

ABSTRACT

The aim of this study was to explore whether (99m)Tc-methoxyisobutylisonitrile ((99m)Tc-MIBI) is suitable to elucidate multidrug resistance and prediction of potentiation of antitumor agents by second-generation MDR1 inhibitors (PSC833, MS-209) in malignant brain tumors in rat. Malignant tumor cells (RG2 and C6 gliomas, Walker 256 carcinoma) were incubated with low dose vincristine (VCR) to induce multidrug resistance. MTT assay demonstrated a significant increase of surviving fractions in VCR-resistant sublines compared to those of drug-naive cells. Reverse transcriptase polymerase chain reaction revealed higher expression of MDR1 mRNA in VCR-resistant cells than drug-naive cells in each line. Volume distribution (V(d)) of (99m)Tc-MIBI was negatively correlated with MDR1 mRNA expression among drug-naive and VCR-resistant cells. MDR1 inhibitors decreased surviving fractions and increased V(d) of (99m)Tc-MIBI significantly in VCR-resistant sublines, whereas MDR1 mRNA expression was unchanged. These findings indicate that (99m)Tc-MIBI efflux was functionally suppressed by MDR1 inhibitors. Autoradiographic images of (99m)Tc-MIBI revealed higher uptake in drug-naive cells at basal ganglia compared with VCR-resistant cells at the opposite basal ganglia of rats. Oral administration of the second-generation MDR1 inhibitors significantly increased (99m)Tc-MIBI accumulation of both tumors. Therapeutic effects of VCR with or without the MDR1 inhibitors were also evaluated autoradiographically using (14)C-methyl-L-methionine ((14)C-Met) and MIB-5 index. (14)C-Met uptake and MIB-5 index of both tumors treated with VCR following the MDR1 inhibitor treatment significantly decreased compared with tumors treated with VCR alone. Analysis of (99m)Tc-MIBI accumulation is considered informative for detecting MDR1-mediated drug resistance and for monitoring the therapeutic effects of MDR1 inhibitors in malignant brain tumors.


Subject(s)
ATP Binding Cassette Transporter, Subfamily B, Member 1/antagonists & inhibitors , Antineoplastic Combined Chemotherapy Protocols/pharmacology , Brain Neoplasms/diagnostic imaging , Brain Neoplasms/drug therapy , Carcinoma 256, Walker/diagnostic imaging , Carcinoma 256, Walker/drug therapy , Technetium Tc 99m Sestamibi , Tomography, Emission-Computed, Single-Photon , ATP Binding Cassette Transporter, Subfamily B, Member 1/genetics , ATP Binding Cassette Transporter, Subfamily B, Member 1/metabolism , Animals , Autoradiography , Brain Neoplasms/metabolism , Carcinoma 256, Walker/metabolism , Cell Line, Tumor , Cell Proliferation/drug effects , Cyclosporine/pharmacology , Cyclosporins/pharmacology , Cytotoxins/pharmacology , Drug Resistance, Neoplasm/drug effects , Drug Resistance, Neoplasm/genetics , Drug Synergism , Predictive Value of Tests , Quinolines/pharmacology , RNA, Messenger/metabolism , Radiopharmaceuticals , Rats , Reverse Transcriptase Polymerase Chain Reaction , Tomography, Emission-Computed, Single-Photon/methods , Vincristine/pharmacology
14.
Nihon Hoshasen Gijutsu Gakkai Zasshi ; 61(9): 1341-8, 2005 Sep 20.
Article in Japanese | MEDLINE | ID: mdl-16192925

ABSTRACT

Three-dimensional imaging with MRI is a useful method for neurosurgical simulations. As in our previous study, we have constructed three-dimensional surface anatomical scanning (3D-SAS) from the data of contrast enhanced 3D fast spoiled gradient recalled acquisition in the steady state (3D-FSPGR) sequence. Using this technique, it is possible to generate 3D images from the data of only one acquisition, without using the fusion function. In our previous study, we did not compare the 3D images with the operative views at surgery. In the present study, two radiologists and one neurosurgeon assessed the 3D images in comparison with the operative views. There were problems in some cases, including unclear cortical sulci owing to brain swelling, lack of depiction of the cortical veins owing to meningeal enhancement, inadequate distinction between pial veins and meningeal veins, and so forth. However, in the majority of cases, 3D-SAS with 3D-FSPGR was able to demonstrate good anatomical conformity with the operative views, indicating the clinical usefulness of this technique.


Subject(s)
Brain Neoplasms/diagnosis , Magnetic Resonance Imaging/standards , Adolescent , Adult , Aged , Brain Neoplasms/pathology , Female , Humans , Imaging, Three-Dimensional , Male , Middle Aged
15.
Nucl Med Biol ; 42(7): 598-607, 2015 Jul.
Article in English | MEDLINE | ID: mdl-25892210

ABSTRACT

INTRODUCTION: We examined whether the amino acid PET tracers, trans-1-amino-3-(18)F-fluorocyclobutanecarboxylic acid (anti-(18)F-FACBC) and (11)C-methyl-l-methionine ((11)C-Met), are suitable for detecting early responses to combination therapies including temozolomide (TMZ), interferon-ß (IFN), and bevacizumab (Bev) in glioblastoma. METHODS: Human glioblastoma U87MG (U87) cells were incubated with low dose TMZ to induce chemoresistance. Both trans-1-amino-3-fluoro-1-(14)C-cyclobutanecarboxylic acid (anti-(14)C-FACBC) and (3)H-methyl-l-methionine ((3)H-Met) uptake were quantified using triple-label accumulation assays to examine the relationship between tracer uptake and proliferation ((3)H-thymidine (TdR) accumulation) in vitro. U87 and U87R (TMZ-resistant subculture) cells were inoculated into the right and left basal ganglia, respectively, of F344/N-rnu rats. The efficacy of single-agent (TMZ, Bev) and combination therapy (TMZ/IFN, TMZ/Bev, TMZ/IFN/Bev) was examined in orthotopic gliomas using MRI, Evans blue extravasation, anti-(14)C-FACBC, and (3)H-Met autoradiography, and MIB-1 immunostaining. RESULTS: TMZ treatment decreased (3)H-TdR accumulation and the volume distribution of anti-(14)C-FACBC and (3)H-Met in U87 but not U87R cells. TMZ/IFN combination therapy significantly decreased these parameters in U87R cells; however, Bev had no additional effect in vitro. In vivo, U87R-derived gliomas were observed as equivocal tumors on MRI and T2-high intensity lesions. Bev treatment, either alone or in combination, markedly decreased U87 enhancing lesions. By contrast, autoradiographic images using anti-(14)C-FACBC and (3)H-Met clearly delineated tumor extent, which spread widely beyond T2-high intensity lesions and enhancing lesions. TMZ therapy significantly decreased tracer accumulation and proliferation of U87- but not U87R-derived tumors. TMZ/IFN combination treatment significantly decreased these parameters in U87R tumors, which were further reduced (in both tumor types) by Bev addition. Tracer uptake correlated with the MIB-1 proliferation index. However, MRI was unsuitable for tumor delineation and assessment of Bev treatment response. CONCLUSIONS: Triple-agent therapy (TMZ/IFN/Bev) was effective against even TMZ-resistant glioblastomas. PET with amino acid tracers provides useful information on the early response of glioblastomas to single-agent and combination therapy.


Subject(s)
Amino Acids/pharmacokinetics , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Brain Neoplasms/drug therapy , Brain Neoplasms/metabolism , Glioblastoma/drug therapy , Glioblastoma/metabolism , Animals , Antineoplastic Agents/administration & dosage , Bevacizumab/administration & dosage , Biomarkers, Tumor/metabolism , Brain Neoplasms/diagnostic imaging , Cell Line, Tumor , Dacarbazine/administration & dosage , Dacarbazine/analogs & derivatives , Glioblastoma/diagnostic imaging , Humans , Interferon-beta/administration & dosage , Male , Positron-Emission Tomography/methods , Radiopharmaceuticals/pharmacokinetics , Rats , Rats, Inbred F344 , Rats, Nude , Reproducibility of Results , Sensitivity and Specificity , Temozolomide , Tissue Distribution , Treatment Outcome
16.
Brain Tumor Pathol ; 32(1): 12-9, 2015 Jan.
Article in English | MEDLINE | ID: mdl-24807101

ABSTRACT

Rapid immunohistochemistry (R-IHC) can contribute to the intraoperative diagnosis of central nervous system (CNS) tumors. We have recently developed a new IHC method based on an alternating current electric field to facilitate the antigen-antibody reaction. To ensure the requirement of R-IHC for intraoperative diagnosis, 183 cases of CNS tumors were reviewed regarding the accuracy rate of diagnosis without R-IHC. The diagnostic accuracy was 90.7 % (166/183 cases) [corrected] in which definitive diagnoses were not provided in 17 cases because of the failure of glioma grading and differential diagnosis of lymphoma and glioma. To establish the clinicopathological application, R-IHC for frozen specimens was compared with standard IHC for permanent specimens. 33 gliomas were analyzed, and the Ki-67/MIB-1 indices of frozen specimens by R-IHC were consistent with the grade and statistically correlated with those of permanent specimens. Thus, R-IHC provided supportive information to determine the grade of glioma. For discrimination between glioma and lymphoma, R-IHC was able to provide clear results of CD20 and Ki-67/MIB-1 in four frozen specimens of CNS lymphoma as well as standard IHC. We conclude that the R-IHC for frozen specimens can provide important information for intraoperative diagnosis of CNS tumors.


Subject(s)
Biomarkers, Tumor/analysis , Brain Neoplasms/diagnosis , Immunohistochemistry/methods , Ki-67 Antigen/analysis , Adolescent , Adult , Aged , Aged, 80 and over , Antigen-Antibody Reactions , Brain Neoplasms/pathology , Diagnosis, Differential , Electricity , Female , Frozen Sections , Glioma/diagnosis , Glioma/pathology , Humans , Intraoperative Period , Lymphoma/diagnosis , Lymphoma/pathology , Male , Middle Aged , Neoplasm Staging , Sensitivity and Specificity , Young Adult
17.
J Nucl Med ; 44(11): 1845-54, 2003 Nov.
Article in English | MEDLINE | ID: mdl-14602869

ABSTRACT

UNLABELLED: Assessments of herpes simplex virus 1 thymidine kinase (HSV-tk)/ganciclovir (GCV) treatment response, early in the course of therapy, are important in the evaluation and clinical management of patients. This study addresses whether imaging amino acid transport, glucose utilization, and passive vascular permeability provides an early indication of treatment response and can predict long-term outcome. METHODS: Fischer 344 rats with intracerebral HSV-tk transduced RG2TK+ xenografts were studied. GCV-treated (50 mg/kg twice daily) and saline-treated control animals were compared; triple-label quantitative autoradiography was performed 3 d after initiating treatment, and long-term survival was determined. Autoradiograms of (18)F-FDG, (67)Ga-diethylenetriaminepentaacetic acid ((67)Ga-DTPA), and (14)C-aminocyclopentane carboxylic acid ((14)C-ACPC) were obtained; measurements of (14)C-ACPC and (67)Ga-DTPA plasma clearance (K(1)), (14)C-ACPC transport ( partial differential K(1)), relative glucose utililization (R), and normalized radioactivity (% dose/g) were obtained in tumor and brain tissues. Adjacent sections were stained to detect apoptotic cells, microvessels, and type L neutral amino acid transporter in tumor and normal brain. RESULTS: GCV treatment reduced partial differential K(1) and % dose/g of (14)C-ACPC in RG2TK+ xenografts to approximately 30% of that in nontreated animals (from 34 +/- 9 [mean +/- SD] to 9.5 +/- 2.7 microL/min/g and from 0.28 +/- 0.09 to 0.11 +/- 0.04 % dose/g, respectively). GCV had a significant but substantially smaller effect than toxicity on glucose utilization and little or no effect on passive vascular permeability of RG2TK+ xenografts. These differences could not be explained by differences in plasma amino acid or glucose concentration at the time of the study. Histology revealed a large fraction of dead tumor cells and only a sparse distribution of apoptotic cells in GCV-treated tumors. Many CD34-positive endothelial cells in GCV-treated tumors showed only weak or marginal LAT1 staining, whereas CD98 staining remained unchanged. Survival was significantly increased by GCV treatment from 18 +/- 4 to 56 +/- 17 d. CONCLUSION: (14)C-ACPC influx, K(1)(ACPC), facilitated transport, partial differential K(1)(ACPC), and % dose/g (ACPC) are good indicators of early treatment response after HSV-tk/GCV gene therapy. The parametric images and changes in K(1)(ACPC), partial differential K(1)(ACPC), and % dose/g (ACPC) are substantial and are better than the corresponding measures obtained in the same animals and in the same tissue (tumor) regions with (67)Ga-DTPA and (18)F-FDG. Amino acid transport imaging may be a good surrogate paradigm to monitor treatment response of brain tumors.


Subject(s)
Autoradiography , Brain Neoplasms/therapy , Cycloleucine/metabolism , Fluorodeoxyglucose F18 , Gallium Radioisotopes , Ganciclovir/pharmacology , Genetic Therapy , Pentetic Acid/metabolism , Simplexvirus/enzymology , Thymidine Kinase/genetics , Animals , Brain Neoplasms/diagnostic imaging , Brain Neoplasms/pathology , Cell Line, Tumor , Humans , Male , Radionuclide Imaging , Rats , Rats, Inbred F344
18.
AJNR Am J Neuroradiol ; 23(9): 1564-7, 2002 Oct.
Article in English | MEDLINE | ID: mdl-12372749

ABSTRACT

We present the case of an infant with medulloblastoma with extensive nodularity, which had been called cerebellar neuroblastoma. MR imaging clearly revealed a nodular enhancement, which appeared as a grape-like lesion. Single photon emission CT revealed markedly high iodine-123 metaiodobenzylguanidine uptake in the enhancing tumor. Iodine-123 metaiodobenzylguanidine single photon emission CT may be useful in the diagnosis of medulloblastoma with extensive nodularity, which has been considered to be a subgroup of medulloblastoma with extensive neuronal differentiation.


Subject(s)
Cerebellar Neoplasms/diagnostic imaging , Medulloblastoma/diagnostic imaging , Tomography, Emission-Computed, Single-Photon , 3-Iodobenzylguanidine , Biopsy , Cerebellar Neoplasms/pathology , Female , Humans , Infant , Iodine Radioisotopes , Medulloblastoma/pathology , Radiopharmaceuticals
19.
J Neurosurg ; 101(6): 989-95, 2004 Dec.
Article in English | MEDLINE | ID: mdl-15597759

ABSTRACT

OBJECT: The authors of this study evaluated the efficacy of simultaneous microscopic and endoscopic monitoring during surgery for internal carotid artery (ICA) aneurysms. METHODS: The endoscopic technique was applied during microsurgery in 11 patients with 13 aneurysms. Nine of these lesions were located on the posterior communicating artery (PCoA), three in the paraclinoid region, and one on the anterior choroidal artery (AChA). Eight patients had unruptured aneurysms and three had ruptured aneurysms. The endoscope was introduced after first exposing the aneurysm through the microscope and was gripped firmly by an airlocked holding arm fitted with a steering system throughout the entire surgery, including dissection of the perforating arteries and application of the aneurysm clips. Regarding paraclinoid aneurysms, clips were applied through direct visualization of the ophthalmic artery and the proximal neck. In a case involving a superior hypophyseal artery aneurysm in the paraclinoid segment, a ring clip was applied without removing the bone structure around the optic canal. In all aneurysms of the PCoA and the AChA, perforating arteries behind the lesion were identified and dissected using endoscopic control. The aneurysm clip was applied in the best position in a single attempt in 10 of 11 patients. There was no surgical complication related to the endoscopic procedures. CONCLUSIONS: Simultaneous monitoring with the microscope and endoscope is extremely useful in applying clips to ICA aneurysms. This combined method allows for direct dissection of the aneurysm, perforating vessels, and the main trunk in an area not visible through the microscope's eyepiece and promises better surgical results.


Subject(s)
Carotid Artery Diseases/surgery , Carotid Artery, Internal/surgery , Endoscopy , Intracranial Aneurysm/surgery , Monitoring, Intraoperative/methods , Adult , Aged , Female , Humans , Male , Microscopy , Microsurgery , Middle Aged , Minimally Invasive Surgical Procedures , Surgical Instruments
20.
J Neurosurg ; 96(6): 1000-5, 2002 Jun.
Article in English | MEDLINE | ID: mdl-12066898

ABSTRACT

OBJECT: The characteristics of a previously unclassified paraclinoid aneurysm arising from the anterolateral (dorsal) wall of the proximal internal carotid artery were retrospectively analyzed in seven patients (five women and two men) who were treated surgically for an aneurysm in this unusual location. METHODS: One patient presented with subarachnoid hemorrhage (SAH) caused by rupture of this aneurysm. The lesions were found incidentally (five cases) or during investigation of SAH due to another aneurysm (one case). There was a female predominance in this series; all female patients harbored multiple aneurysms. All patients underwent surgery. Removal of the anterior clinoid process was necessary because the proximal neck of the aneurysm was closely adjacent to the dural ring. CONCLUSIONS: This special group of aneurysms is very rare, is located exclusively in the intradural space, and carries the risk of SAH. The results of surgical treatment for this aneurysm are quite satisfactory.


Subject(s)
Carotid Artery, Internal/diagnostic imaging , Carotid Artery, Internal/surgery , Intracranial Aneurysm/diagnostic imaging , Intracranial Aneurysm/surgery , Sphenoid Bone/diagnostic imaging , Sphenoid Bone/surgery , Aged , Carotid Artery, Internal/physiopathology , Cerebral Angiography , Cerebrovascular Circulation/physiology , Craniotomy , Female , Humans , Intracranial Aneurysm/physiopathology , Male , Middle Aged , Retrospective Studies , Sphenoid Bone/physiopathology
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