Ki Uk Kim

A case of subdural hematoma in patient with chronic myeloid leukemia treated with high-dose imatinib mesylate

Imatinib mesylate (IM) is used to treat a wide range of diseases, including Philadelphia chromosome-positive chronic myeloid leukemia (CML), on account of its high tolerability and low incidence of minor adverse events. Hemorrhage is thought to be a rare complication of IM. Recently, IM has been associated with reduced α2-plasmin inhibitor and platelet dysfunction. We report here the case of a 33-year-old female patient with CML who experienced subdural hematoma after an incremental increase in IM dosage due to a loss of complete molecular response. This case indicates that physicians should be alert to this atypical cause of headache in patients taking high-dose IM.

Intracranial plasma cell granuloma.

Plasma cell granuloma is a tumor-like disease characterized by non-neoplastic polyclonal proliferation of plasma cells and other mononuclear cells. This disease occurs most frequently in the lung and upper respiratory tract, while the involvement of the central nervous system is very rare. A 44-year-old female patient presented with nausea and progressive visual disturbance. Brain magnetic resonance imaging (MRI) revealed the mass along the right tentorium with low signal intensity in the T2 weighted image (T2WI) and fluid-attenuated inversion recovery (FLAIR) sequence, and an isosignal intensity in T1 weighted image (T1WI), the latter of which was enhanced after administration of gadolinium-diethylenetriamine penta-acetic acid (Gd-DTPA). The thickest portion of the tentorium was partially excised via the combined suboccipital and infratentorial approach. The histopathological examination indicated a diagnosis of plasma cell granuloma. Postoperative steroid therapy was administered for remnant tumor control. Although a follow up MRI scan taken 20 months after the operation showed a slight decrease in tumor size, the lesion had extended to the falx and left frontal convexity along with parenchymal edema at 32 months after the operation and the clinical status was aggravated. The mass was removed from the left frontal convexity. Radiation therapy was given, together with steroid administration.

Pituitary hemorrhage : classification and related factors.

OBJECTIVE Clinical features of pituitary hemorrhage vary from asymptomatic to catastrophic. The purpose of this study was to evaluate the factors related to severity of hemorrhage of pituitary adenoma. METHODS Pituitary hemorrhage was noted in 32 of 88 patients who underwent operations between January 2000 and December 2007. Clinical status was classified into group I (no hemorrhage symptoms), II (mild to moderate symptoms without neurological deficit), and III (with neurological deficit), and was compared to radiological, pathological, and operative findings. All patients were operated by transsphenoidal approach, and hemorrhage-related symptoms were relieved. RESULTS Groups I, II, and III comprised 15, 10 and 7 patients, respectively. In group I, hemorrhage volume was under 1 mL in 11 (73.3%), but, it was above 1 mL in 7 (70%) of group II and in all cases of group III. Hemorrhage stage based on MRI findings was chronic or subacute in 11 (73.3%) of group I, acute in 6 (60%) of group II, and acute or hyperacute in 6 (85.7%) of group III. Pathological examination revealed chronic-stage hematomas in 5 (50%) group II patients. Functioning adenomas were found in 5 (33.3%) group I patients but none in group II or III patients. Silent adenomas were found in 4 (26.7%), 8 (80%), and 3 (42.9%) in groups I, II, and III, respectively. CONCLUSION Clinical features of pituitary hemorrhage may differ with the radiological and immunohistopathlogical findings. Persistent symptoms are related to the chronic stage of hematoma requiring surgery for symptom relief. Neurological deficits are caused by large amount of acute hemorrhage requiring emergency operation. Silent adenoma is related to the severity of pituitary hemorrhage.

Clinical Analysis of Patients who Survived for Less than 3 Months After Brain Metastatectomy

In the patients with brain metastasis (BM), it is impossible to determine who will benefit from surgery because of limited survival. In an attempt to identify optimal candidates for brain metastatectomy, we analyzed patients who survived for <3 months after craniotomy for a single BM lesion. Between January 1st, 1997 and July 31st, 2007, 83 patients with a single BM underwent craniotomy. Of these patients, 25 patients (30.1%) died within 3 months of craniotomy. The primary lesions were non-small call lung cancer in 15, colon cancer in 6, and breast cancer, renal cell carcinoma, ovarian cancer, or esophageal cancer in one apiece. Of the 25 patients, 19 (79%) were of tumor stage IV and had extra-cranial metastasis. Eleven (44%) of the 25 primary cancers had a well-controlled status. Twelve patients (48%) had a Karnofsky Performance Scale (KPS) score of <70, and 13 (52%) were of Recursive Partitioning Analysis (RPA) class 3. Primary cancer status, RPA class, and functional status were found to be critical factors for consideration when selecting surgical candidates. In addition, adjuvant therapy was found to have an important role on survival.

Prognostic Role of Methylation Status of the MGMT Promoter Determined Quantitatively by Pyrosequencing in Glioblastoma Patients.

Objective This study investigated whether pyrosequencing can be used to determine the methylation status of the MGMT promoter as a clinical biomarker using relatively old archival tissue samples of glioblastoma. We also examined other prognostic factors for survival of glioblastoma patients. Methods The available study set included formalin-fixed paraffin-embedded (FFPE) tissue from 104 patients at two institutes from 1997 to 2012, all of which were diagnosed histopathologically as glioblastoma. Clinicopathologic data were collected by review of medical records. For pyrosequencing analysis, the PyroMark Q96 CpG MGMT kit (Qiagen, Hilden, Germany) was used to detect the level of methylation at exon 1 positions 17–39 of the MGMT gene, which contains 5 CpGs. Results Methylation of the MGMT promoter was detected in 43 (41.3%) of 104 samples. The average percentage methylation was 14.0±16.8% overall and 39.0±14.7% for methylated cases. There was no significant pattern of linear increase or decrease according to the age of the FFPE block (p=0.687). In multivariate analysis, age, performance status, extent of surgery, method of adjuvant therapy, and methylation status estimated by pyrosequencing were independently associated with overall survival. Additionally, patients with a high level of methylation survived longer than those with low methylation (p=0.016). Conclusion In this study, the status and extent of methylation of the MGMT promoter analyzed by pyrosequencing were associated with overall survival in glioblastoma patients. Pyrosequencing is a quantitative method that overcomes the problems of MSP and a simple technique for accurate analysis of DNA sequences.

Immunotoxin therapy for primary malignant brain tumors

Abstract The prognosis of malignant brain tumors is poor in spite of aggressive treatment. Immunotoxin therapy is a novel approach for the treatment of tumors. Targeted fusion toxins, chimeric protein consisting of the cytotoxic domain of the natural toxin and carrier ligands such as a growth factor or an antibody, have been introduced in the treatment of malignant central nervous system (CNS) tumors, with promising results. The toxin is internalized into the cytosol of the target cell via cell-surface receptors and it is essential for these receptors on the tumor cell to be highly expressed in order for the immunotoxin to have specific anti-tumor activity. Studies on expression of cell-surface receptor for immunotoxin targeting was performed on transferring (TR), insulin-like growth factor-1 (IGF-1R), and interleukin-4 (IL-4R) receptors of human glioblastoma (U373-MG and T98-G) and medulloblastoma (Daoy) cell lines, and the effect of irradiation on expressibility of these receptors was studied. Recombinant diphtheria toxin–murine interleukin-4 conjugate (DT 390 –mIL4) was developed and its cytotoxic efficacy against murine glioblastoma (SMA-560) and neuroblastoma (Neuro-2a and NB41-A3) cell lines was examined, and the combined effect with irradiation was tested. Receptors were expressed in all cases except IGF-1R on T98-G. After irradiation, TR expression was increased for Daoy, IGF-1R expression was increased on Daoy and U373-MG, and IL-4R expression was decreased on Daoy and U373-MG. DT 390 –mIL4 exhibited dose-dependent, specific cytotoxic effects on all cell lines tested with IC 50 (concentration of DT 390 –mIL4 that inhibit 50% of protein synthesis) value of 0.56×10 −9 M in SMA-560, 1.28×10 −9 M in Neuro-2a and 0.95×10 −10 M in NB41-A3. Cytotoxicity was additive when DT 390 –mIL4 at 10 −9 M was administered with irradiation. Targeted fusion toxins are characterized by great potency and high specificity with minimal damage to normal neuronal tissue, and interleukin-4 receptor is one of the proper targets for fusion toxin. The cytotoxicity of the immunotoxin is additive when it is administrated with irradiation. Targeted toxin therapy is a promising adjuvant treatment modality for the malignant brain tumors.

Relationship Between Cytogenetic Complexity and Peritumoral Edema in High-Grade Astrocytoma

Background The purpose of the study is to reveal the association of cytogenetic compltyexi and peritumoral edema volume (PTEV) and its prognostic significance in high-grade astrocytoma patients by culturing patient tumor cells. Methods Twenty-seven high-grade astrocytoma patients were divided into three groups according to karyotype complexity: normal, non-complex karyotype (NCK), and complex karyotype (CK). Endothelial growth factor receptor (EGFR) amplification was detected by FISH, and its association with chromosome 7 abnormalities was analyzed. Mean PTEV of each group was compared by ANOVA to evaluate the relationship between PTEV and cytogenetic complexity. Results The PTEV of patients in normal (n=6), NCK (n=8), and CK (n=13) groups were 24.52±17.73, 34.26±35.04, and 86.31±48.7 cm3, respectively (P=0.005). Ten out of 11 patients with EGFR amplification showed abnormalities in chromosome 7. The mean PTEV of EGFR-amplified and non-amplified groups were 80.4±53.7 and 41.3±37.9 cm3, respectively (P=0.035). The average survival of patients with PTEV less than 90 cm3 was 30.52±26.11 months, while in patients with PTEVs over or equal to 90 cm3, it was 10.83±5.53 months (P=0.007). Conclusions The results show an association of complex karyotype with the PTEV of high-grade astrocytoma. EGFR amplification plays a significant role in the formation of peritumoral edema, causing PTEV to increase, which is related with survival. This implies that cytogenetic karyotype can be applied as a prognostic factor.

Novalis Stereotactic Radiosurgery for Spinal Dural Arteriovenous Fistula

The spinal dural arteriovenous fistula (SDAVF) is rare, presenting with progressive, insidious symptoms, and inducing spinal cord ischemia and myelopathy, resulting in severe neurological deficits. If physicians have accurate and enough information about vascular anatomy and hemodynamics, they achieve the good results though the surgery or endovascular embolization. However, when selective spinal angiography is unsuccessful due to neurological deficits, surgery and endovascular embolization might be failed because of inadequate information. We describe a patient with a history of vasospasm during spinal angiography, who was successfully treated by spinal stereotactic radiosurgery using Novalis system.