Epigenetic Role of Histone 3 Lysine Methyltransferase and Demethylase in Regulating Apoptosis Predicting the Recurrence of Atypical Meningioma.

Alteration of apoptosis is related with progression and recurrence of atypical meningiomas (AMs). However, no comprehensive study has been conducted regarding histone modification regulating apoptosis in AMs. This study aimed to determine the prognostic values of certain apoptosis-associated factors, and examine the role of histone modification on apoptosis in AMs. The medical records of 67 patients with AMs, as diagnosed during recent 13 yr, were reviewed retrospectively. Immunohistochemical staining was performed on archived paraffin-embedded tissues for pro-apoptotic factors (CASP3, IGFBP, TRAIL-R1, BAX, and XAF1), anti-apoptotic factors (survivin, ERK, RAF1, MDM2, and BCL2), and the histone modifying enzymes (MLL2, RIZ, EZH1, NSD2, KDM5c, JMJD2a, UTX, and JMJD5). Twenty-six (38.8%) patients recurred during the follow-up period (mean duration 47.7 months). In terms of time-to-recurrence (TTR), overexpression of CASP3, TRAIL-R1, and BAX had a longer TTR than low expression, and overexpression of survivin, MDM2, and BCL2 had a shorter TTR than low expression (P<0.05). Additionally, overexpression of MLL2, UTX, and JMJ5 had shorter TTRs than low expression, and overexpression of KDM5c had a longer TTR than low expression. However, in the multi-variate analysis of predicting factors for recurrence, low expression of CASP3 (P<0.001), and BAX (P<0.001), and overexpression of survivin (P=0.007), and MDM2 (P=0.037) were associated with recurrence independently, but any enzymes modifying histone were not associated with recurrence. Conclusively, this study suggests certain apoptosis-associated factors should be associated with recurrence of AMs, which may be regulated epigenetically by histone modifying enzymes.

Results of immunohistochemical staining for cell cycle regulators predict the recurrence of atypical meningiomas.

OBJECT: The aim of this study was to evaluate the role of certain cell-cycle regulatory proteins in the recurrence of atypical meningiomas. These proteins were analyzed with immunohistochemical staining to identify predisposing factors for the recurrence of atypical meningiomas. METHODS: The authors retrospectively reviewed the medical records of patients with atypical meningiomas diagnosed in the period from January 2000 to June 2012 at the Department of Neurosurgery at Samsung Changwon Hospital and Dong-A University Medical Center. Clinical data included patient sex and age at the time of surgery, presenting symptoms at diagnosis, location and size of tumor, extent of surgery, use of postoperative radiotherapy, duration of follow-up, and recurrence. Immunohistochemical staining for cell-cycle regulatory proteins (p16, p15, p21, p27, cyclin-dependent kinase [CDK] 4 and 6, phosphorylated retinoblastoma [pRB] protein, and cyclin D1) and proliferative markers (MIB-1 antigen, mitosis, and p53) was performed on archived paraffin-embedded tissues obtained during resection. The recurrence rate and time to recurrence were assessed using Kaplan-Meier analysis. RESULTS: Of the 67 atypical meningiomas eligible for analysis, 26 (38.8%) recurred during the follow-up period (mean duration 47.7 months, range 8.4-132.1 months). Immunohistochemically, there was overstaining for p16 in 44 samples (65.7%), for p15 in 21 samples (31.3%), for p21 in 25 samples (37.3%), for p27 in 32 samples (47.8%), for CDK4 in 38 samples (56.7%), for CDK6 in 26 samples (38.8%), for pRB protein in 42 samples (62.7%), and for cyclin D1 in 49 samples (73.1%). Multivariate analysis using the Cox proportional-hazards regression model showed that incomplete resection (HR 4.513, p < 0.001); immunohistochemical understaining for p16 (HR 3.214, p < 0.001); immunohistochemical overstaining for CDK6 (HR 3.427, p < 0.001), pRB protein (HR 2.854, p = 0.008), and p53 (HR 2.296, p = 0.040); and increased MIB-1 labeling index (HR 2.665, p = 0.013) and mitotic index (HR 2.438, p = 0.024) predicted the recurrence of atypical meningiomas after resection. CONCLUSIONS: Findings in this study indicated that p16, CDK6, and pRB protein were associated with the recurrence of atypical meningiomas.

Assessment of depression, anxiety, sleep disturbance, and quality of life in patients with chronic low back pain in Korea.

BACKGROUND: Chronic low back pain (CLBP) has a significant effect on quality of life and imposes a great economical burden on society. In a number of studies, validated questionnaires had been given to CLBP patients to determine their health-associated quality of life, sleep disturbance, and psychological status. However, such outcome studies had not been performed previously in Korea. METHODS: We used self-report questionnaires to compare CLBP patients with an age- and sex-matched healthy control group. Between September 2012 and August 2013, we enrolled 47 patients who had CLBP for more than 3 months (group P) and 44 healthy age- and sex-matched controls (group C), who completed the following self-report questionnaires: 36-Item Short Form Health Survey (SF-36), Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI), Oswestry Disability Index (ODI), and Pittsburgh Sleep Quality Index (PSQI). RESULTS: The scores from the ODI, BDI, and BAI were significantly higher in group P than in group C. The SF-36 scores were significantly lower in group P than in group C, suggesting lower quality of life in group P. The incidence of depression and anxiety was significantly higher in group P than in group C. However, neither the PSQI score nor the incidence of sleep disturbance was significantly different between the groups. CONCLUSIONS: Patients with CLBP showed considerable functional disability and significant impairment of psychological status with a low quality of life. Hence, it is important to evaluate CLBP patients to provide adequate psychological support.

Results of immunohistochemical staining of cell-cycle regulators: the prediction of recurrence of functioning pituitary adenoma.

OBJECTIVE: This study was undertaken primarily to investigate the possible prognostic values of several cell-cycle regulators for the prediction of functioning pituitary adenoma (FPA) recurrence after surgical resection by immunohistochemically analyzing tumor samples obtained by surgical resection. METHODS: The medical records of the patients with FPA diagnosed from January 2000 to December 2009 at the Department of Neurosurgery at Samsung Changwon Hospital and Dong-A University Medical Center were selected. Immunohistochemical staining was performed on archived paraffin-embedded tissues obtained by surgical resection for adenohypophysial cells, cell-cycle regulatory proteins (p16, p15, p21, cyclin-dependent kinase [CDK] 4 and 6, phosphorylated retinoblastoma [pRB] protein, and cyclin D1), MIB-1 antigen, and p53. RESULTS: Of the 174 FPAs, 62 (35.6%) recurred during follow-up period (mean duration 62.4 months, range 24.2-118.9 months). Immunohistochemically, overstaining for p16 in 89 samples (51.1%), p15 in 27 samples (15.5%), p21 in 20 samples (11.5%), CDK4 in 54 samples (31.0%), CDK6 in 18 samples (10.3%), pRB protein in 69 samples (39.7%), and cyclin D1 in 87 samples (50.0%). Multivariate analysis using the Cox proportional hazard regression model showed that invasion into cavernous sinus (hazard ratio [HR] of 4.02; P < 0.001), immunohistochemical normostaining for p16 (HR of 3.16; P < 0.001), immunohistochemical overstaining for pRB protein (HR of 2.45; P = 0.008), cyclin D1 (HR of 2.13; P = 0.029), MIB-1 antigen (HR of 2.74; P = 0.002), and p53 (HR of 2.21; P = 0.002), predicted the recurrence of FPA after surgical resection. CONCLUSIONS: Our findings indicate that p16, pRB protein, and cyclin D1 are associated with recurrence FPA after surgical resection.

Comparisons of 30-day mortalities and 90-day functional recoveries after first and recurrent primary intracerebral hemorrhage attacks: a multiple-institute retrospective study.

BACKGROUND: The aim of this study was to determine and compare 30-day mortalities and 90-day functional recoveries after first and recurrent primary intracerebral hemorrhage (PICH) attacks. The investigators sought to identify factors predisposing 30-day mortality and functional recovery and to compare patients after first and recurrent PICH attacks. METHODS: The medical records of 1856 PICH patients treated in Samsung Changwon Hospital and Dong-A University Medical Center from January 2000 to December 2010 were retrospectively evaluated. RESULTS: Of these 1856 patients, 1499 were included. Mean patient age was 66.4 ± 16.3 years, and there were 742 male patients (49.5%). Recurrent PICH occurred in 142 (9.5%) patients. Thirty-day mortality was 13.6% for first PICH patients and 14.1% for recurrent PICH patients (P = 0.824). Good functional recovery at 90 days after ictus was achieved by 52.2% of first PICH patients and by 31.0% of recurrent patients (P = 0.003). In both groups, multivariate analysis showed that unconsciousness, pupillary abnormality, surgery, and underlying disease were associated with high mortality, and that consciousness, a lobal location, a small hemorrhagic volume, and conservative treatment were associated with good functional recovery. After excluding recurrent patients with a previous moderate to severe disability due to the sequelae of PICH, no difference was found between the first (25.1%) and recurrent groups (19.0%) in terms of functional recovery (P = 0.083). CONCLUSIONS: The factors found to predispose clinical outcome were similar in the two groups. This study shows that given optimal treatment, recurrent PICH patients can achieve the same clinical outcomes as first PICH patients.

Clinically significant cardiac arrhythmia in patients with aneurysmal subarachnoid hemorrhage.

OBJECTIVE: Many previous studies have shown that electrocardiographic (ECG) changes occur patients with subarachnoid hemorrhage (SAH). This study was designed to identify the frequency, influencing factors, and outcome of clinically significant cardiac arrhythmias after SAH. METHODS: We retrospectively analyzed clinical data of 122 patients including ECG finding, age, sex, the Hunt-Hess grade, the Fisher's grade, the history of hypertension, peak blood pressure and heart rate, location of aneurysm, Glasgow Outcome Scale (GOS) score, the days of admission to the intensive care unit, the presence of symptomatic vasospasm. RESULTS: Of 122 SAH patients, 50% (n = 61) had a verified clinically significant arrhythmia. There were no statistically significant independent factors associated with clinically significant arrhythmia in multivariate analysis. Although adjustments for the effects of age, Hunt-Hess grade, and the presence of symptomatic vasospasm on death were made, clinically significant arrhythmias were still independently predictive of death (no arrhythmia versus arrhythmia, 11.5% versus 27.9%, adjusted odds ratio [OR] 3.524, 95% confidence interval [CI] 1.229-10.100, p = 0.019) and poor outcome (GOS ≤ 2, 13.1% versus 29.5%, adjusted OR 3.202, 95% CI 1.174-8.732, p= 0.023). CONCLUSION: Clinically significant arrhythmias after SAH are associated with a high mortality rate, and serious cardiac and neurological comorbidity. Patients with an abnormal ECG on admission should undergo close cardiac monitoring, and the presence of rhythm disturbances should prompt aggressive measures to treat myocardial infarction (MI), maintain a normal cardiac rhythm, and minimize the presence of autonomic stress.

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.

Olfactory schwannoma-case report-.

Intracranial schwannomas preferentially arise from the vestibular branch of the eighth nerve, and rarely from the trigeminal nerve, facial nerve, and lower cranial nerves. Anterior cranial fossa schwannomas are extremely uncommon and few details about them have been reported. The patient was a 39-year-old woman whose chief complaints were anosmia and frontal headache for 2 years. The gadolinium (Gd)-enhanced magnetic resonance imaging (MRI) showed an extra-axial mass from ethmoid sinus to right frontal base region near the midline, with solid enhancement in lower portion and multicystic formation in upper portion. The tumor was totally resected via basal subfrontal approach. At operation, the tumor had cystic portion with marginal calcification and the anterior skull base was destructed by the tumor. The olfactory bulb was involved, and the tumor capsule did not contain neoplastic cells. The histopathological diagnosis was schwannoma. We report a rare case of anterior cranial fossa schwannoma with literature review.

Removal of intradural-extramedullary spinal cord tumors with unilateral limited laminectomy.

Total laminectomy for the removal of intradural-extramedullary spinal cord tumors has been used widely, but postoperative complications often develop, such as kyphosis, spinal instability, and persistent back pain. In this study, we evaluated seven patients with intradural-extramedullary spinal cord tumors with respect to the value of unilateral limited laminectomy. Our cases included six schwannomas, and one meningioma. The cervical region was involved in four cases, the thoracolumbar region in two cases, and the lumbar region in one case. The rationale for choosing a unilateral approach is to preserve musculoligamentous attachments and posterior bony elements as much as possible. The patients were mobilized on the third postoperative day and preoperative neurological symptoms were recovered within a few weeks. We did not observe any complication relating to unilateral limited laminectomy and at follow-up evaluation (at 3 and 12 months postoperatively), none of the patients showed spinal deformity or spinal instability. We think that the unilateral limited laminectomy is a safe and efficient technique for the treatment of intradural-extramedullary spinal cord tumors. We suggest that this technique is one of the best treatments for these tumors.

Predisposing factors related to shunt-dependent chronic hydrocephalus after aneurysmal subarachnoid hemorrhage.

OBJECTIVE: Hydrocephalus is a common sequelae of aneurysmal subarachnoid hemorrhage (SAH) and patients who develop hydrocephalus after SAH typically have a worse prognosis than those who do not. This study was designed to identify factors predictive of shunt-dependent chronic hydrocephalus among patients with aneurysmal SAH, and patients who require permanent cerebrospinal fluid diversion. METHODS: Seven-hundred-and-thirty-four patients with aneurysmal SAH who were treated surgically between 1990 and 2006 were retrospectively studied. Three stages of hydrocephalus have been categorized in this paper, i.e., acute (0-3 days after SAH), subacute (4-13 days after SAH), chronic (>/=14 days after SAH). Criteria indicating the occurrence of hydrocephalus were the presence of significantly enlarged temporal horns or ratio of frontal horn to maximal biparietal diameter more than 30% in computerized tomography. RESULTS: Overall, 66 of the 734 patients (8.9%) underwent shunting procedures for the treatment of chronic hydrocephalus. Statistically significant associations among the following factors and shunt-dependent chronic hydrocephalus were observed. (1) Increased age (p < 0.05), (2) poor Hunt and Hess grade at admission (p < 0.05), (3) intraventricular hemorrhage (p < 0.05), (4) Fisher grade III, IV at admission (p < 0.05), (5) radiological hydrocephalus at admission (p < 0.05), and (6) post surgery meningitis (p < 0.05) did affect development of chronic hydrocephalus. However the presence of intracerebral hemorrhage, multiple aneurysms, vasospasm, and gender did not influence on the development of shunt-dependent chronic hydrocephalus. In addition, the location of the ruptured aneurysms in posterior cerebral circulation did not correlate with the development of shunt-dependent chronic hydrocephalus. CONCLUSION: Hydrocephalus after aneurysmal SAH seems to have a multifactorial etiology. Understanding predisposing factors related to the shunt-dependent chronic hydrocephalus may help to guide neurosurgeons for better treatment outcomes.