Stereotactic radiosurgery for brain metastases from hepatocellular carcinoma

The purpose of this study is to investigate the possible role of stereotactic radiosurgery (SRS) in the management of patients with brain metastases from hepatocellular carcinoma (HCC). Thirty-two consecutive patients with 80 brain metastases from HCC were treated with SRS. Twenty-eight (87.5 %) patients were male, and the mean age of the patients was 54 ± 12 years (range 22–73). Twenty-seven (84.4 %) patients were classified as RTOG RPA Class 2. The mean tumor volume was 6.14 ± 11.3 cm³ (range 0.01–67.3). The mean marginal dose prescribed was 20.1 ± 3.6 Gy (range 10.0–25.0). The median overall survival time after SRS was 11.3 ± 5.8 weeks (95 % CI 0–22.7). A greater total volume of brain metastases (>14 cm³) was the only independent prognostic factor (HR = 2.419; 95 % CI 1.040–5.624; p = 0.040). The actuarial control rate of brain metastases was 51.3 % at 4 months after SRS. The prescribed marginal dose (>18 Gy) was significantly related with the actuarial tumor control (HR = 0.254; 95 % CI 0.089–0.725; p = 0.010). The prognosis of patients with brain metastases from HCC is dismal even with the modern technology of radiosurgery. The marginal dose prescribed should be reevaluated to improve upon the current poor local control rates.     

Great hospitals of Asia: the Department of Neurosurgery at Seoul National University College of Medicine

Established in 1957, the Department of Neurosurgery at Seoul National University College of Medicine is the one of the oldest neurosurgical departments in Korea. The seven past Chairmen (Bo Sung Sim, Kil Soo Choi, Dae Hee Han, Byung-Kyu Cho, Hyun Jib Kim, Hee-Won Jung, and Dong Gyu Kim) have devoted themselves to the development of the department. The current chair, Chun Kee Chung, assumed the position in July 2010. The current department comprises several clinical programs that encompass the entire spectrum of neurosurgical disorders, with 29 specialized faculty members and care teams in three hospitals: Seoul National University Hospital (SNUH), Boramae Medical Center (BMC), and Seoul National University Bundang Hospital (SNUBH). The remarkable growth of the department during the last half century made it possible to perform 5,666 operations (3,299 at SNUH, 411 at BMC and 1,860 at SNUBH) during 2009. A total of 1,201 articles authored by faculty members were published in scientific journals between 1958 and 2009, approximately 32% of which were published in international journals. The department is regarded as the "Mecca" of neurosurgery in Korea because of its outstanding achievement and the many distinguished alumni with leadership roles in the academic field. This article traces the clinical, academic, and scientific development of the department, its present activities, and its future direction.     

Papillary glioneuronal tumors: a review of clinicopathologic and molecular genetic studies

This study was designed to evaluate 4 new cases of papillary glioneuronal tumors (PGNTs), 2 of which had atypical histologic features, provides extensive IHC characterization, performed comparative genomic hybridization in 2 of our cases, and reviews the recent literature. The study group comprised 3 women and 1 man, with ages ranging from 12 to 75 years. Patients presented with seizures (n = 3) or muscle spasm (n = 1), and the tumors were located in the supratentorial region of the brain (3 in the frontal and 1 in the parietotemporal lobe). The 2 atypical tumors showed a moderately high mitotic rate (4 and 7/10 HPF, each), vascular endothelial hyperplasia, and necrosis. Tumor cells expressed both neuronal and glial markers, but the degree of neuronal versus glial expression was varied. None of the tumors expressed p53, EGFR wild type/vIII, IDH1, or CD34; however, nestin, galectin-3, and S100 were positive in the tumor cells. No EGFR gene amplification or 1p/19q deletion was found by fluorescence in situ hybridization. Half of the cases revealed PTEN loss by immunohistochemistry, and MGMT methylation was positive in 3 cases by MGMT methylation-specific polymerase chain reaction. Ultrastructurally, either astrocytic or neuronal differentiation was observed, but we could not identify any hybrid cells. An array-based comparative genomic hybridization study revealed loss of 1q, 6p, 8p, 9p, 9q, and 16q and gain of 2q, 3p, 5q, 6p, 7q, 10q, 16q, 19p, and 22q in 2 cases simultaneously. The first patient, who underwent subtotal resection, died because of progression of the tumor within 9 months after surgery; however, 2 patients were symptom free and progression free at 34 and 48 months after gross total resection (the patient 2: plus radiotherapy, the patient 3: no adjuvant chemo- or radiotherapy). The last patient developed seizures after a long symptom-free period (40 mo) with no evidence of tumor recurrence. Our 4 new cases, in conjunction with the literature review, reinforce that PGNTs are tumors that usually occur in young adults (mean age, 24 y); they are most often cystic with a mural nodule or are cystic/solid, supratentorial, closely located with the ventricle, molecularly genetically different from astrocytic or oligodendroglial tumors, and indolent in behavior. Cases (2 of 4 in our study) with atypical histologic features or that occur in advanced age (75 y), and sporadic reports of histologically or biologically aggressive PGNTs, serve to remind pathologists that the full spectrum of PGNTs is as yet unknown.     

Gamma knife radiosurgery for central neurocytoma: primary and secondary treatment

BACKGROUND: Little is known about long-term results of gamma knife (GK) stereotactic radiosurgery (SRS) as a primary or a secondary postoperative therapy for central neurocytomas (CNs). The authors retrospectively reviewed long-term outcomes of 13 patients with CN treated with GK SRS. METHODS: Thirteen patients were treated with GK SRS as a primary (6 patients) or a secondary postoperative therapy (7 patients). Follow-up clinical status and brain magnetic resonance imaging (MRI) were thoroughly analyzed. The functional status of patients was assessed with the Karnofsky Performance Scale during follow-up. RESULTS: The median follow-up period for clinical status and imaging studies was 61 months (range, 6 months to 96 months). Tumors decreased in 5 patients who received GK SRS as a primary treatment. However, the tumor recurred in 2 patients treated with a secondary GK SRS after surgery from the residual tumor bed that was not covered by the GK SRS. Parenchymal changes and secondary malignancies were not found in follow-up MRIs of all 13 patients. The Karnofsky Performance Scale score of all patients, except for 1 patient who suffered from an unrelated anteriorly communicating arterial aneurysmal rupture, did not change after GK SRS. CONCLUSIONS: GK SRS may be useful as a primary or a secondary postoperative therapy for the treatment of CN. However, more attention should be paid to residual or recurrent CN during treatment, and regular long-term follow-up MRI should be mandatory to validate the procedure.     

Falx Meningiomas: Surgical Results and Lessons Learned from 68 Cases

Objective

The purpose of this study was to review the characteristics of falcine meningioma retrospectively and to identify the parameters associated with tumor recurrence.

Methods

The analysis included; age, sex, extent of resection, and radiologic and pathologic findings. Falcine meningiomas were classified by location as anterior, middle, or posterior as described for parasagittal meningiomas.

Results

Of the 795 meningioma patients treated between 1990 and 2004 at the authors'' institution, 68 patients with meningiomas arising from the falx underwent craniotomies. There were 22 male and 46 female patients (1 : 2.1). Mean age was 55 years and ranged from 14 to 77 years. Locations of falcine meningioma were; the anterior third in 33 cases, middle in 20, and posterior in 15. Mean tumor volume was 42 cc and ranged from 4 to 140 cc. In 58 of the 68 patients tumors were totally removed. Additional surgery for recurrence was performed in 6 patients over 15 years. Of these 6 patients, only two patients underwent gross total tumor resection at first operation; the other four underwent subtotal tumor resection. Based on pathologic reports, the largest tumor subtype was transitional. There were four patients with a high grade tumor-three atypical and one anaplastic meningioma. Of the 68 patients, 59 achieved a good outcome (no neurological deficit or recurrence), six had temporary complications, two suffered new permanent postoperative deficits, and the remaining one died due to severe brain swelling despite postoperative intensive care. Extent of surgical resection was found to be significantly related to tumor recurrence.

Conclusion

Falcine meningioma accounted for 8.5% of intracranial meningiomas and the transitional meningioma was the most common subtype of falcine meningioma. Gross total resection of tumor was the single most important predictor of an improved surgical outcome.     

Antitumor activity of CKD-602, a camptothecin derivative, in a mouse glioma model

CKD-602 (7-[2-(N-isopropylamino)ethyl]-(20S)-camptothecin, belotecan), a novel synthetic water-soluble camptothecin derivative, is known to have a significant anticancer effect in vitro on human glioma cell lines, including U87MG and U251MG. In the present study, we evaluated the in vivo antitumor effect of CKD-602 in a mouse glioma model. Nude mice with established U87MG glioma were treated with a dose of CKD-602 of 0mg/kg (control group, injection with saline only; n=5), 40 mg/kg (group A) or 60 mg/kg (group B). Thereafter, the dose was repeated once every 4 days for a total of four doses. Tumor volume was measured histologically and apoptosis was detected using the terminal deoxynucleotide transferase dUTP nick end labeling (TUNEL) assay and immunofluorescence analysis with cleaved caspase-3. Mean tumor volume in each group was: control, 145.35 mm(3); group A, 76.51 mm(3); group B, 73.99 mm(3)). Tumor volume was significantly smaller in both groups A and B compared with the control group (group A, p<0.01; group B, p<0.05). Apoptosis of tumor cells was evident to a greater extent in groups A and B relative to the control group, but there were no significant differences in tumor volume or apoptotic index between groups A and B. These results suggest that CKD-602 has a significant anticancer effect on glioma cells in vivo.     

The role of chemotherapy in anaplastic astrocytoma patients

Objective

This retrospective study was performed to evaluate the role of chemotherapy in the management of patients with anaplastic astrocytoma (AA).

Methods

We compared the survival outcome among the 3 different treatment protocol groups in a single institution. A total of 86 patients (39 men and 47 women) with newly diagnosed AA after surgery were analyzed. Among them, 31 patients (36.0%) were treated with radiotherapy only (RT Group), 30 patients (34.9%) were treated with nimustine-cisplatin chemotherapy before RT (ACNU-CDDP group), and 25 patients (29.1%) were treated with procarbazine, lomustine and vincristine (PCV) chemotherapy after radiotherapy (PCV group).

Results

The median survival was 14.0, 30.0 and 72.0 months in RT, ACNU-CDDP, and PCV group, respectively and showed significant differences (RT vs. ACNU-CDDP; p=0.039, RT vs. PCV; 0.002, ACNU-CDDP vs. PCV; 0.045). PCV group showed less toxicity rate (5 patients; 20%) than ACNU-CDDP group (12 patients; 40%), while only 3 patients (9.6%) in RT group experienced grade 3 or 4 toxicities.

Conclusion

An application of chemotherapy before or after radiotherapy is beneficial in prolonging the survival of patients with AA. Adjuvant PCV chemotherapy after radiotherapy is recommendable.     

Mechanism for enhanced 5-aminolevulinic acid fluorescence in isocitrate dehydrogenase 1 mutant malignant gliomas

Fluorescence-guided surgery using 5-aminolevulinic acid (5-ALA) has become the main treatment modality in malignant gliomas. However unlike glioblastomas, there are inconsistent result about fluorescence status in WHO grade III gliomas. Here, we show that mutational status of IDH1 is linked to 5-ALA fluorescence. Using genetically engineered malignant glioma cells harboring wild type (U87MG-IDH1^WT) or mutant (U87MG-IDH1^R132H) IDH1, we demonstrated a lag in 5-ALA metabolism and accumulation of protoporphyrin IX (PpIX) in U87MG-IDH1^R132H cells. Next, we used liquid chromatography–mass spectrometry (LC-MS) to screen for tricarboxylic acid (TCA) cycle-related metabolite changes caused by 5-ALA exposure. We observed low baseline levels of NADPH, an essential cofactor for the rate-limiting step of heme degradation, in U87MG-IDH1^R132H cells. High levels of NADPH are required to metabolize excessive 5-ALA, giving a plausible reason for the temporarily enhanced 5-ALA fluorescence in mutant IDH1 cells. This hypothesis was supported by the results of metabolic screening in human malignant glioma samples. In conclusion, we have discovered a relationship between enhanced 5-ALA fluorescence and IDH1 mutations in WHO grade III gliomas. Low levels of NADPH in tumors with mutated IDH1 is responsible for the enhanced fluorescence.     

Primary diffuse leptomeningeal glioneuronal tumors

Brain Tumor Pathology - Diffuse leptomeningeal disseminated glioneuronal tumor (DL-GNT) is a rare brain tumor that presents as a plaque-like subarachnoid tumor, commonly involving the basal...     

Investigation of molecular factors associated with malignant transformation of oligodendroglioma by proteomic study of a single case of rapid tumor progression

Purpose Frozen tumor tissues from a patient who showed rapid progression to anaplastic oligodendroglioma after near total resection of oligodendroglioma were used to examine differential expression of proteins to gain better understanding of the pathogenesis of malignant transformation. Methods We have determined their protein profiles using a 2D gel electrophoresis and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry approach. Results Among 23 differentially expressed spots, overexpression of peroxiredoxin 6 and underexpression of rho GDP dissociation inhibitor alpha were confirmed to be valid after western blot and immunocytochemical analysis of oligodendroglioma tissue. Conclusions Abnormal expression of peroxiredoxin 6 and rho GDP dissociation inhibitor alpha may be associated with malignant transformation in oligodendroglioma and these proteins might be candidates of molecular predictive factors.