Underexpression of HOXA11 Is Associated with Treatment Resistance and Poor Prognosis in Glioblastoma / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Homeobox (HOX) genes are essential developmental regulators that should normally be in the silenced state in an adult brain. The aberrant expression of HOX genes has been associated with the prognosis of many cancer types, including glioblastoma (GBM). This study examined the identity and role of HOX genes affecting GBM prognosis and treatment resistance. MATERIALS AND METHODS: The full series of HOX genes of five pairs of initial and recurrent human GBM samples were screened by microarray analysis to determine the most plausible candidate responsible for GBM prognosis. Another 20 newly diagnosed GBM samples were used for prognostic validation. In vitro experiments were performed to confirm the role of HOX in treatment resistance. Mediators involved in HOX gene regulation were searched using differentially expressed gene analysis, gene set enrichment tests, and network analysis. RESULTS: The underexpression of HOXA11 was identified as a consistent signature for a poor prognosis among the HOX genes. The overall survival of the GBM patients indicated a significantly favorable prognosis in patients with high HOXA11 expression (31±15.3 months) compared to the prognoses in thosewith low HOXA11 expression (18±7.3 months, p=0.03). When HOXA11 was suppressed in the GBM cell lines, the anticancer effect of radiotherapy and/or temozolomide declined. In addition, five candidate mediators (TGFBR2, CRIM1, TXNIP, DPYSL2, and CRMP1) that may confer an oncologic effect after HOXA11 suppression were identified. CONCLUSION: The treatment resistance induced by the underexpression of HOXA11 can contribute to a poor prognosis in GBM. Further investigation will be needed to confirm the value of HOXA11 as a potential target for overcoming the treatment resistance by developing chemo- or radiosensitizers.

Sclerosing Meningioma : Radiological and Clinical Characteristics of 21 Cases

OBJECTIVE: A rare subtype of meningioma, sclerosing meningioma is not included in the current World Health Organization classification of meningiomas and is classified into the category of other morphological variation subtypes. Sclerosing meningioma is often misdiagnosed to other non-benign meningioma or malignant neoplasm, so it is important to diagnose sclerosing type correctly. We analyzed the radiological and clinical characteristics of a series of sclerosing meningiomas. METHODS: Twenty-one patients who underwent surgery in one institute with a histopathologically proven sclerosing meningioma were included from 2006 to 2014. Eighteen tumors were diagnosed as a pure sclerosing-type meningioma, and 3 as mixed type. Magnetic resonance image was taken for all patients including contrast enhancement image. Computed tomography (CT) scan was taken for 16 patients. One neuroradiologist and 1 neurosurgeon reviewed all images retrospectively. RESULTS: In the all 16 patients with preoperative CT images, higher attenuation was observed in the meningioma than in the brain parenchyma, and calcification was observed in 11 (69%). In 15 of the 21 patients (71%), a distinctive very low signal intensity appeared as a dark color in T2-weighted images. Nine of these 15 tumors (60%) exhibited heterogeneous enhancement, and 6 (40%) exhibited homogeneous enhancement that was unlike the homogeneous enhancing pattern shown by conventional meningiomas. Ten patients had a clear tumor margin without peritumoral edema. CONCLUSION: Although these peculiar radiological characteristics are not unique to sclerosing meningioma, we believe that they are distinctive features that may be helpful for distinguishing sclerosing meningioma from other subtypes.

Adult Intracranial Gliofibroma : A Case Report and Review of the Literature

Gliofibroma is an extremely rare biphasic tumor with an astrocytic and benign mesenchymal component, which commonly occurs within the first two decades of life. The exact biological behavior of the tumor is not fully understood. Therefore, it is not listed as a distinct entity in the current World Health Organization classification of central nervous system tumors. Here, we describe a rare case of gliofibroma, which was located on the medial temporal lobe in a 61-year-old woman. Preoperatively, we misdiagnosed it as a meningioma because it was a well-demarcated and well-enhanced extra-axial mass with calcification and bony destruction. On the histopathological and immunohistochemical examination, the tumor consisted of a mixture of glial tissue and mesenchymal tissue and it was finally diagnosed as a gliofibroma. To our knowledge, this case of intracranial gliofibroma is in the oldest patient ever reported.

Transfusion-Related Acute Lung Injury (TRALI) in Patients with Aneurysmal Subarachnoid Hemorrhage (SAH) / 대한뇌혈관외과학회지

OBJECTIVE: Transfusion-related acute lung injury (TRALI) is a poorly understood, but life-threatening complication after transfusion of blood components. The present study was conducted to identify the incidence of TRALI in patients with aneurysmal subarachnoid hemorrhage (SAH) as well as to determine the risk factors for TRALI. METHODS: This retrospective study was carried out on our institute, during the period of Jan. 2006 and Dec. 2008 to a total of 237 patients who underwent microsurgical treatment for aneurysmal SAH. In this time period, 154 patients were finally enrolled in this study. Patients' demographics, clinical and radiographic factors relevant to the aneurysms and SAH, and parameters regarding transfusion were analyzed and compared. RESULTS: A total of 9 patients had TRALI among a total of 154 patients. The incidence of TRALI was 0.01% (9 in 836) for all transfused blood component, and 0.06% (9 in 154) for all transfused patients. Statistical analysis showed that Fisher grade III and IV (OR, 1.88; 95% CI, 1.13-3.07) and total amount of transfused units exceeding 1,200cc (OR 1.72; 95% CI, 1.22-2.65) were associated with the development of TRALI. On the other hand, sex, poor Hunt-Hess Grade (IV and V), preoperative hemoglobin less than 13, postoperative hemoglobin less than 11, use of volume expander, premorbid disease (hypertension, diabetes) were not associated with TRALI. CONCLUSIONS: The results of present study indicate that large amount SAH and transfusion of blood components more than 1,200cc are risk factors for the development of TRALI. Prospectively designed study with a larger cohort is mandated to confirm the etiology and risk factors of TRALI in stroke practice.

Incidence and Risk Factors of Infection Caused by Vancomycin-Resistant Enterococcus Colonization in Neurosurgical Intensive Care Unit Patients

OBJECTIVE: This study was aimed to identify the incidence and risk factors of vancomycin-resistant enterococcus (VRE) colonization in neurosurgical practice of field, with particular attention to intensive care unit (ICU). METHODS: This retrospective study was carried out on the Neurosurgical ICU (NICU), during the period from January. 2005 to December. 2007, in 414 consecutive patients who had been admitted to the NICU. Demographics and known risk factors were retrieved and assessed by statistical methods. RESULTS: A total of 52 patients had VRE colonization among 414 patients enrolled, with an overall prevalence rate of 6.1%. E. faecium was the most frequently isolated pathogen, and 92.3% of all VRE were isolated from urine specimen. Active infection was noticed only in 2 patients with bacteremia and meningitis. Relative antibiotic agents were third-generation cephalosporin in 40%, and vancomycin in 23%, and multiple antibiotic usages were also identified in 13% of all cases. Multivariate analyses showed Glasgow coma scale (GCS) score less than 8, placement of Foley catheter longer than 2 weeks, ICU stay over 2 weeks and presence of nearby VRE-positive patients had a significantly independent association with VRE infection. CONCLUSION: When managing the high-risk patients being prone to be infected VRE in the NICU, extreme caution should be paid upon. Because prevention and outbreak control is of ultimate importance, clinicians should be alert the possibility of impending colonization and infection by all means available. The most crucial interventions are careful hand washing, strict glove handling, meticulous and active screening, and complete segregation.

Traumatic Brainstem Hemorrhage Presenting with Hemiparesis

Traumatic brainstem hemorrhage after blunt head injury is an uncommon event. The most frequent site of hemorrhage is the midline rostral brainstem. The prognosis of these patients is poor because of its critical location. We experienced a case of traumatic brainstem hemorrhage. A 41-year-old male was presented with drowsy mentality and right hemiparesis after blunt head injury. Plain skull radiographs and brain computerized tomography scans revealed a depressed skull fracture, epidural hematoma, and hemorrhagic contusion in the right parieto-occipital region. But, these findings did not explain the right hemiparesis. T2-weighted magnetic resonance (MR) image of the cervical spine demonstrated a focal hyperintense lesion in the left pontomedullary junction. Brain diffusion-weighted and FLAIR MR images showed a focal hyperintensity in the ventral pontomedullary lesion and it was more prominent in the left side. His mentality and weakness were progressively improved with conservative treatment. We should keep in mind the possibility of brainstem hemorrhage if supratentorial lesions or spinal cord lesions that caused neurological deficits in the head injured patients are unexplainable.

Spinal Subdural Hemorrhage as a Cause of Post-Traumatic Delirium

A 64-year-old man with TBI was admitted to our institute. In following days, he showed unusual behavior of agitation, restlessness, emotional instability and inattention. Post-traumatic delirium was tentatively diagnosed, and donepezil was given for his cognitive dysfunction. Although there was partial relief of agitation, he sustained back pain despite medication. Lumbar magnetic resonance image revealed SDH along the whole lumbar spine, and surgical drainage was followed. Postoperatively, his agitation disappeared and further medication was discontinued. We report a unique case of post-traumatic delirium in a patient with concomitant TBI and spinal subdural hemorrhage (SDH) that resolved with operative drainage of spinal hemorrhage.