Tumor Spheroids of an Aggressive Form of Central Neurocytoma Have Transit-Amplifying Progenitor Characteristics with Enhanced EGFR and Tumor Stem Cell Signaling

Central neurocytoma (CN) has been known as a benign neuronal tumor. In rare cases, CN undergoes malignant transformation to glioblastomas (GBM). Here we examined its cellular origin by characterizing differentiation potential and gene expression of CN-spheroids. First, we demonstrate that both CN tissue and cultured primary cells recapitulate the hierarchal cellular composition of subventricular zone (SVZ), which is comprised of neural stem cells (NSCs), transit amplifying progenitors (TAPs), and neuroblasts. We then derived spheroids from CN which displayed EGFR+/ MASH+ TAP and BLBP+ radial glial cell (RGC) characteristic, and mitotic neurogenesis and gliogenesis by single spheroids were observed with cycling multipotential cells. CN-spheroids expressed increased levels of pluripotency and tumor stem cell genes such as KLF4 and TPD5L1, when compared to their differentiated cells and human NSCs. Importantly, Gene Set Enrichment Analysis showed that gene sets of GBM-Spheroids, EGFR Signaling, and Packaging of Telomere Ends are enriched in CN-spheroids in comparison with their differentiated cells. We speculate that CN tumor stem cells have TAP and RGC characteristics, and upregulation of EGFR signaling as well as downregulation of eph-ephrin signaling have critical roles in tumorigenesis of CN. And their ephemeral nature of TAPs destined to neuroblasts, might reflect benign nature of CN.

Tumor Spheroids of an Aggressive Form of Central Neurocytoma Have Transit-Amplifying Progenitor Characteristics with Enhanced EGFR and Tumor Stem Cell Signaling

Central neurocytoma (CN) has been known as a benign neuronal tumor. In rare cases, CN undergoes malignant transformation to glioblastomas (GBM). Here we examined its cellular origin by characterizing differentiation potential and gene expression of CN-spheroids. First, we demonstrate that both CN tissue and cultured primary cells recapitulate the hierarchal cellular composition of subventricular zone (SVZ), which is comprised of neural stem cells (NSCs), transit amplifying progenitors (TAPs), and neuroblasts. We then derived spheroids from CN which displayed EGFR+/ MASH+ TAP and BLBP+ radial glial cell (RGC) characteristic, and mitotic neurogenesis and gliogenesis by single spheroids were observed with cycling multipotential cells. CN-spheroids expressed increased levels of pluripotency and tumor stem cell genes such as KLF4 and TPD5L1, when compared to their differentiated cells and human NSCs. Importantly, Gene Set Enrichment Analysis showed that gene sets of GBM-Spheroids, EGFR Signaling, and Packaging of Telomere Ends are enriched in CN-spheroids in comparison with their differentiated cells. We speculate that CN tumor stem cells have TAP and RGC characteristics, and upregulation of EGFR signaling as well as downregulation of eph-ephrin signaling have critical roles in tumorigenesis of CN. And their ephemeral nature of TAPs destined to neuroblasts, might reflect benign nature of CN.

Frameless Fractionated Gamma Knife Radiosurgery with ICON™ for Large Metastatic Brain Tumors

BACKGROUND: Recently, a new generation of gamma knife radiosurgery (GKRS) equipped with a frameless immobilization system has encouraged the use of fractionated GKRS as an increasingly favorable treatment option. We investigated the preliminary outcome of efficacy and toxicity associated with frameless fractionated gamma knife radiosurgery (FF GKRS) for the treatment of large metastatic brain tumors. METHODS: Fifteen patients with 17 lesions were treated using FF GKRS and included in this study, because of the large tumor size of more than 10 cm3. FF GKRS was performed based on a thermoplastic mask system for 3 to 5 consecutive days. RESULTS: The mean duration of clinical follow-up was 12 months (range, 4–24), and the local control rate was 100%. Tumor volume decreased in 13 lesions (76.5%), and remained stable in 4 lesions (23.5%). One patient was classified as new lesion development because of the occurrence of leptomeningeal seeding regardless of the tumor volume change. Compared with the initial volume at the time of FF GKRS, tumor volume change at the last follow-up was 62.32% ± 29.80%. Cumulative survival rate at 12 months was 93.3% ± 6.4%. One patient died during the follow-up period because of the progression of the primary disease. No patient showed radiation necrosis on the follow-up images. CONCLUSION: Daily FF GKRS by gamma knife ICON™ revealed satisfactory tumor control rate and low morbidity, despite the short follow-up period. Further prospective studies and a longer follow-up of a large cohort of patients diagnosed with brain metastases are required to elucidate the effect of FF GKRS in brain metastases.

Fractionated Gamma Knife Radiosurgery as Initial Treatment for Large Skull Base Meningioma

We present our experience on the hypofractionated Gamma Knife radiosurgery (FGKS) for large skull base meningioma as an initial treatment. We retrospectively reviewed 23 patients with large skull base meningioma ≥10 cm³ who underwent FGKS as the initial treatment option. The mean volume of tumors prior to radiosurgery was 21.2±15.63 cm³ (range, 10.09~71.42). The median total margin dose and marginal dose per fraction were 18 Gy (range, 15~20) and 6 Gy (range, 5~6), respectively. Patients underwent three or four fractionations in consecutive days with the same Leksell® frame. The mean follow-up duration was 38 months (range, 17~78). There was no mortality. At the last follow-up, the tumor volume was stationary in 15 patients (65.2%) and had decreased in 8 patients (34.8%). Six patients who had cranial neuropathy at the time of FGKS showed improvement at the last clinical follow-up. Following FGKS, 4 patients (17%) had new cranial neuropathy. The trigeminal neuropathy was the most common and all were transient. The mean Karnofsky Performance Status score at pre-FGKS and the last clinical follow-up was 97.0±10.4 points (median, 100) and 98.6±6.9 (median, 100) points, respectively. FGKS has showed satisfactory tumor control with functional preservation for large skull base meningiomas. Further prospective studies of large cohorts with long term follow-up are required to clarify the efficacy in the tumor control and functional outcome as well as radiation toxicity.

A Minimally Invasive Lumbar Spine Surgery Technique Using a Modified Thoracoport: Proposal of a New Tubular Retractor

Recently the trend of surgical procedure for treatment of lumbar benign disease is a minimally invasive surgery due to small incision, minimal blood loss, and a short hospital day. By using a microscope or an endoscope, and other surgical equipment, a delicate manipulation in a narrow space became feasible, consequently, to secure a wider view with small incision, appropriate retractors are required. But the various tubular retractor systems are expensive and have some problems. We modified Thoracoport (Auto Suture Co., Norwalk, CT) by making a window at the distal end of trocar and used it as a tubular retractor in surgical procedure for treatment of lumbar benign disease. This modified tubular retractor is docked closely on the curved lamina and provides a wider view. We used it as a tubular retractor also in lumbar bilateral decompression involving a unilateral approach. But this trocar has the limited sizes (diameter and length), and also it is difficult to fix the retractor or change the direction of retractor. And then, we propose a more modified Thoracoport with various sizes and attaching the settling holders to the head of tubular retractor to be able to fix the retractor.

Cost Analysis for the Management of Cerebral Aneurysms: Comparison between Clipping and Coiling / 대한뇌혈관외과학회지

OBJECTIVE: The aim of this study is to compare the costs for the management of ruptured or unruptured cerebral aneurysms during hospital stay between surgical and endovascular treatment under the Korean national health insurance system. METHODS: It is a retrospective analysis of 301 cases that had been managed for cerebral aneurysms by clipping and/or coiling at Gil Medical Center from January 2003 to December 2004. Of 301 cases, 37 patients were excluded because they were managed by clipping and coiling at the same hospital stay or for the same aneurysm, had cerebral arteriovenous malformations also, and died during acute postoperative period. The authors analyzed the costs for hospital stay, laboratory test, medications, surgeon's fee, anesthetic fee and disposable medical supplies. We analyzed the costs only for the treatment of cerebral aneurysms and eliminated the expenses for other coexisting diseases, rehabilitation, and long-term follow-up. All statistical analyses were performed by using SPSS software version 11.5 (SPSS Institute Inc., Chicago, IL). RESULTS: The total number of clipping group was 208 and of coiling was 56. The total mean cost (in Won, \) per patient with ruptured aneurysm in the clipping group and coiling group were \16,986,009+/-\3,037,006 and \18,685,125+/-\4,519,573, respectively. For the unruptured aneurysm, the total mean cost per patient were \16,871,981+/-\3,434,005 in clipping, and \16,383,267+/-\2,480,184 in coiling. Coiling group resulted in shorter hospital stay and less medication, but there was no statistically significant difference in the total mean cost between clipping and coiling. CONCLUSION: Although coiling group had a shorter hospital stay and less medication costs than clipping group, the total mean cost for coiling was more than clipping without statistical significance because the costs of disposable medical supplies for the coiling were much more expensive than those for the clipping under the current Korean national insurance system.

Degloving Injuries / 대한정형외과학회잡지

No abstract available in English.

A Clinical Study of the Malgaigne Fractures / 대한정형외과학회잡지

The incidence of pelvic fractures with or without dislocation of the sacro-iliac or symphysis pubis, is continually increasing. Such injuries not only are serious but can result in disabling complications and deaths. The author reviewed 57 cases of Malgaigne fractures treated at the orthopedic department of Kyungpook National University Hospital during the period from January 1978 to December 1977, and analized as to the cause of injury by mechanical forces, type of fracture, average duration for treatment and complications. We have adopted the classification of unstable fractures of Dunn and Morris. The fractures were classified as followes: vertical shear, 11: bucket handle, 8: lateral compression, 6: straddle, 5: total pelvic disruption, 4: dislocation, 3. Twenty-four patients were male thirteen, female. Traffic accident caused the injury in twenty-seven of the patients, accident of mine and factory, each three. Two fell from heights. Frequent associated soft tissue injuries were rupture of bladder (6 patients) and rupture of urethra (10 patients) The principle of treatment consisted of skeletal traction through the lower limb (supracondyle of femur) on the involved side and balance skin traction on the normal side. Pelvic sling were used. In lateral compression type, reduction was obtained by application of lateral skeletal traction with pelvic screw. Traction was continued for eight weeks. After discarding the traction physiotherapy start in bed and continued for further four weeks. Complete reduction of the displaced fragment and an adequate period of immobilization in recumbency is necessary to obtain the best results in treatment of Malgaigne fractures.