Relationship between postoperative hypothalamic injury and water and sodium disturbance in patients with craniopharyngioma: A retrospective study of 178 cases.

Objective: To investigate the relationship between postoperative hypothalamo-hypophyseal injury (HHI) and postoperative water and sodium disturbances in patients with craniopharyngioma. Methods: The medical records, radiological data, and laboratory results of 178 patients (44 children and 134 adults) who underwent microsurgery for craniopharyngioma in a single center were reviewed. Postoperative HHI was assessed using magnetic resonance imaging. Structural defects of the hypothalamo-hypophyseal system (pituitary, pituitary stalk, floor and lateral wall of the third ventricle) were assessed in four standard T1-weighted images. The defect of each structure was assigned 1 score (0.5 for the unilateral injury of the third ventricle wall), and a HHI score was calculated. Results: The number of patients with HHI scores of 0-1, 2, 2.5-3, and >3 was 35, 49, 61, and 33, respectively. Diabetes insipidus (DI) worsened in 56 (31.5%) patients with preoperative DI, while 119 (66.9%) patients were diagnosed with new-onset DI. Hypernatremia and hyponatremia developed in 127 (71.3%) and 128 (71.9%) patients after surgery, respectively. Syndrome of inappropriate antidiuresis occurred in 97(54.5%) patients. During hospitalization, hypernatremia recurred in 33 (18.5%) patients and in 54 (35.7%) during follow-up, of which 18 (11.9%) were severe. DI persisted in 140 (78.7%) patients before discharge. No relationship was found between the HHI score and incidence of early DI, hyponatremia, syndrome of inappropriate diuretic hormone, or prolonged DI. Compared with patients with a score of 0-1, those with scores =2.5-3 (OR = 5.289, 95% CI:1.098-25.477, P = 0.038) and >3 (OR = 10.815, 95% CI:2.148-54.457, P = 0.004) had higher risk of developing recurrent hypernatremia. Patients with a score >3 had higher risk of developing severe hypernatremia during hospitalization (OR = 15.487, 95% CI:1.852-129.539, P = 0.011) and at follow-up (OR = 28.637, 95% CI:3.060-267.981, P = 0.003). Conclusions: The neuroimaging scoring scale is a simple tool to semi-quantify HHI after surgery. Recurrent and severe hypernatremia should be considered in patients with a high HHI score (>2.5). An HHI score >3 is a potential predictor of adipsic DI development. Preventive efforts should be implemented in the perioperative period to reduce the incidence of potentially catastrophic complications.

Solitary Fibrous Tumor of Central Nervous System: Clinical and Prognostic Study of 24 Cases.

BACKGROUND: Solitary fibrous tumors (SFTs) are rare mesenchymal tumors that occasionally occur in the central nervous system (CNS). It is difficult to fully understand their clinical characteristics, partly due to a limited number of reported cases. METHODS: We reviewed 24 patients admitted to our institution between 2009 and 2016 with CNS solitary fibrous tumors. We reviewed and analyzed patient profiles, such as demographics, presentations, imaging studies, extent of resection, and adjuvant treatment. Differences between malignant and benign SFTs were assessed using the χ2 test or Student's t-test. Kaplan-Meier analysis was used to estimate the disease-free survival (DFS) rate. The multivariate Cox regression analysis was performed to evaluate the possible predictive value of the DFS rate of the previously mentioned covariates. RESULTS: A total of 13 men and 11 women were enrolled in the study (the average age was 43). The median follow-up time was 58 months. Twenty-one patients underwent gross total resection (GTR), and 3 patients received a subtotal resection (STR). The tumors in 15 patients (62.5%) were atypical or malignant. One patient (4.2%) suffered SFT-related death (multiple organ failure by tumor metastasis), and 3 patients (12.5%) experienced tumor recurrence. We found that a large tumor size (≥10 cm, P < 0.001) and STR (P < 0.001) were negatively associated with the DFS rate. CONCLUSION: CNS SFTs are rare, slow-growing, less aggressive, and recrudescent tumors. Complete resection is the most effective therapy. Large tumor size and STRs might shorten DFS time.

Microsurgical Management of Craniopharyngiomas via a Unilateral Subfrontal Approach: A Retrospective Study of 177 Continuous Cases.

OBJECTIVE: To evaluate the outcomes of 177 cases of craniopharyngioma (CP) treated via a unilateral subfrontal approach. METHODS: A total of 177 continuous microscopic surgeries were performed by the senior author (Y.X.). The tumors were divided into 6 groups using the diaphragm sellae and the third ventricle floor as the anatomic references. The preoperative, postoperative, and long-term follow-up data were analyzed to evaluate the extent of tumor resection, recurrence, and functional status. RESULTS: The subfrontal-basal approach was used in 169 (91.4%) cases. Total resection was achieved in 167 (94.4%) cases. A total of 158 patients were followed from 6 to 130 months. There were 3 perioperative and 23 delayed deaths. Twenty-two patients had tumor recurrence (12.7%). The progression-free survival was 80% at 5 years and 72% at 10 years. The overall survival was 84.0% at 2.5 years and 83.2% at 10 years. There was a significant increase of pituitary dysfunction after total resection. Neurologic function was stable in most patients. Rate of hypothalamic dysfunction and mortality were higher in patients with intraventricular CPs. Of the surviving patients, 91.8% were living independently with acceptable morbidities at the end of the study. CONCLUSIONS: Most CPs extend along the intrasellar-suprasellar-third ventricle axis. A subfrontal-basal approach is a simple, safe, and effective approach to resecting CPs extending along the vertical axis. A translamina terminalis approach is an ideal corridor to resect intraventricular CP. The benefit of radical resection remains controversial, especially for CPs involving the infundibulotuberal region.

Effect of ATorvastatin On Chronic subdural Hematoma (ATOCH): a study protocol for a randomized controlled trial.

BACKGROUND: Chronic subdural hematoma (CSDH) is a common disease that is more prevalent in older people. Surgical intervention is a safe treatment of choice. However, the recurrence rate is relatively high and the outcome is not always satisfactory among surgically treated patients. It is believed that aberrant angiogenesis and intracapsular inflammation contribute to the development of CSDH. Atorvastatin is reported to promote angiogenesis and suppress inflammation. We have recently shown that atorvastatin is effective to non-surgically reduce and eliminate CSDH with minimal side effects. Here, we report a clinical research trial protocol that is designed to evaluate the therapeutic effects of atorvastatin on CSDH. METHODS/DESIGN: We have designed a multi-center, randomized, placebo-controlled, double blind clinical trial for evaluating the efficacy of oral atorvastatin in reducing CSDH. We have so far recruited 96 patients with CT-confirmed or MRI-confirmed CSDHs from 16 medical centers in China. These patients were originally recruited for the Oriental Neurosurgical Evidence-based Study Team (ONET) study. After informed consent is provided, patients are randomized to receive either atorvastatin (oral 20 mg/night for 8 weeks) or placebo (dextrin for 8 weeks); and followed for 16 weeks after the treatment. The primary outcome is the change in hematoma volume at the end of 8-week treatment. Secondary outcomes include: changes in 1) the hematoma volume at the 4(th), 12(th), and 24(th) weeks; 2) Markwalder's Grading Scale and Glasgow Coma Scale (MGS-GCS); 3) Glasgow Outcome Score (GOS) and 4) Activities of Daily Life-the Barthel Index scale (ADL-BI). Safety will be assessed during the study by monitoring adverse events, laboratory tests, electrocardiography (ECG), measurements of vital signs (temperature, pulse, and blood pressure) and body weight. DISCUSSION: Results of this trial will provide critical information regarding whether atorvastatin is an effective and safe alternative to surgical treatment of CSDH. TRIAL REGISTRATION: ClinicalTrials.gov Identifier--NCT02024373 The date of trial registration: 7 August 2013.

Anti-cancer effect of metabotropic glutamate receptor 1 inhibition in human glioma U87 cells: involvement of PI3K/Akt/mTOR pathway.

BACKGROUND: Metabotropic glutamate receptors (mGluRs) are G-protein-coupled receptors that mediate neuronal excitability and synaptic plasticity in the central nervous system, and emerging evidence suggests a role of mGluRs in the biology of cancer. Previous studies showed that mGluR1 was a potential therapeutic target for the treatment of breast cancer and melanoma, but its role in human glioma has not been determined. METHODS: In the present study, we investigated the effects of mGluR1 inhibition in human glioma U87 cells using specific targeted small interfering RNA (siRNA) or selective antagonists Riluzole and BAY36-7620. The anti-cancer effects of mGluR1 inhibition were measured by cell viability, lactate dehydrogenase (LDH) release, TUNEL staining, cell cycle assay, cell invasion and migration assays in vitro, and also examined in a U87 xenograft model in vivo. RESULTS: Inhibition of mGluR1 significantly decreased the cell viability but increased the LDH release in a dose-dependent fashion in U87 cells. These effects were accompanied with the induction of caspase-dependent apoptosis and G0/G1 cell cycle arrest. In addition, the results of Matrigel invasion and cell tracking assays showed that inhibition of mGluR1 apparently attenuated cell invasion and migration in U87 cells. All these anti-cancer effects were ablated by the mGluR1 agonist L-quisqualic acid. The results of western blot analysis showed that mGluR1 inhibition overtly decreased the phosphorylation of PI3K, Akt, mTOR and P70S6K, indicating the mitigated activation of PI3K/Akt/mTOR pathway. Moreover, the anti-tumor activity of mGluR1 inhibition in vivo was also demonstrated in a U87 xenograft glioma model in athymic nude mice. CONCLUSION: The remarkable efficiency of mGluR1 inhibition to induce cell death in U87 cells may find therapeutic application for the treatment of glioma patients.

miR-124a restoration inhibits glioma cell proliferation and invasion by suppressing IQGAP1 and ß-catenin.

A number of microRNAs have been identified to be important regulators of tumorigenesis. Previous research has shown that miR-124 is abundantly expressed in normal brain tissue; however, only a few reports have focused on the biological impact of miR-124 on glioma cells, and the underlying mechanisms need to be elucidated. Therefore, we investigated the effect of miR-124a on glioma cell proliferation and invasion; furthermore, the underlying molecular mechanism was examined. The present study demonstrated that miR-124a expression was downregulated in human glioma tissues, and its expression level was negatively correlated with the pathological grade of the glioma. Restoration of miR-124a inhibited glioma cell proliferation and invasion in vitro. Furthermore, we found that miR-124a directly targeted and suppressed IQ motif containing GTPase activating protein 1 (IQGAP1), a well-known regulator of actin dynamics and cell motility. RNA interference assay showed that IQGAP1 knockdown led to downregulation of ß-catenin and downstream cyclin D1. Taken together, our study revealed that miR-124a could inhibit glioma cell proliferation and invasion by blocking the expression of the IQGAP1 gene and downstream ß-catenin and cyclin D1. This research may provide a useful molecular therapy for gliomas.

Downregualtion of dynamin-related protein 1 attenuates glutamate-induced excitotoxicity via regulating mitochondrial function in a calcium dependent manner in HT22 cells.

Glutamate-mediated excitotoxicity is involved in many acute and chronic brain diseases. Dynamin related protein 1 (Drp-1), one of the GTPase family of proteins that regulate mitochondrial fission and fusion balance, is associated with apoptotic cell death in cancer and neurodegenerative diseases. Here we investigated the effect of downregulating Drp-1 on glutamate excitotoxicity-induced neuronal injury in HT22 cells. We found that downregulation of Drp-1 with specific small interfering RNA (siRNA) increased cell viability and inhibited lactate dehydrogenase (LDH) release after glutamate treatment. Downregulation of Drp-1 also inhibited an increase in the Bax/Bcl-2 ratio and cleavage of caspase-9 and caspase-3. Drp-1 siRNA transfection preserved the mitochondrial membrane potential (MMP), reduced cytochrome c release, enhanced ATP production, and partly prevented mitochondrial swelling. In addition, Drp-1 knockdown attenuated glutamate-induced increases of cytoplasmic and mitochondrial Ca(2+), and preserved the mitochondrial Ca(2+) buffering capacity after excitotoxicity. Taken together, these results suggest that downregulation of Drp-1 protects HT22 cells against glutamate-induced excitatory damage, and this neuroprotection may be dependent at least in part on the preservation of mitochondrial function through regulating intracellular calcium homeostasis.

Tumstatin transfected into human glioma cell line U251 represses tumor growth by inhibiting angiogenesis.

BACKGROUND: Angiogenesis is a prerequisite for tumor growth and plays an important role in rapidly growing tumors, such as malignant gliomas. A variety of factors controlling the angiogenic balance have been described, and among these, the endogenous inhibitor of angiogenesis, tumstatin, has drawn considerable attention. The current study investigated whether expression of tumstatin by glioma cells could alter this balance and prevent tumor formation. METHODS: We engineered stable transfectants from human glioma cell line U251 to constitutively secrete a human tumstatin protein with c-myc and polyhistidine tags. Production and secretion of the tumstatin-c-myc-His fusion protein by tumstatin-transfected cells were confirmed by Western blotting analysis. In the present study, we identify the anti-angiogenic capacity of tumstatin using several in vitro and in vivo assays. Student's t-test and one-way analysis of variance (ANOVA) test were used to determine the statistical significance in this study. RESULTS: The tumstatin transfectants and control transfectants (stably transfected with a control plasmid) had similar in vitro growth rates compared to their parental cell lines. However, the conditioned medium from the tumstatin transfected tumor cells significantly inhibits proliferation and causes apoptosis of endothelial cells. It also inhibits tube formation of endothelial cells on Matrigel. Examination of armpit tumors arising from cells overexpressing tumstatin repress the growth of tumor, accompanying the decreased density of CD31 positive vessels in tumors ((5.62 ± 1.32)/HP), compared to the control-transfectants group ((23.84 + 1.71)/HP) and wild type U251 glioma cells group ((29.33 + 4.45)/HP). CONCLUSION: Anti-angiogenic gene therapy using human tumstatin gene may be an effective strategy for the treatment of glioma.

Expression and functional significance of ezrin in human brain astrocytoma.

Ezrin is overexpressed in a variety of neoplastic cells and is involved in the later stages of tumor progression and metastasis. The present study investigated the expression and functional significance of ezrin in human brain astrocytoma. Ezrin expression was examined in specimens from healthy human brains (10 autopsies) or human astrocytoma (107 cases) by immunohistochemistry. All healthy specimens were negative for ezrin expression, while this expression was positive in a great majority of human astrocytoma tissues (96/107; 89.7%; p < 0.05 vs. healthy). Ezrin expression was positively correlated with tumor grade (r = 0.551, p < 0.01). Analysis of clinicopathologic data revealed that the post-operation disease-free survival times were significantly (p < 0.001) different between those with a strong positive ezrin expression and those with a weak or negative expression. Specifically, median DFS in patients with a strongly positive ezrin expression was 13 months (range 2-46 months), while it was significantly (p < 0.001) longer in patients with weakly positive or negative expression (median of 28 months, range 6-56 months). In conclusion, there is a strong association between ezrin expression and increased malignancy in astrocytoma. Thus, enhanced ezrin expression may play an important role in the development of astrocytoma. Our results further indicate that ezrin may be useful for grading of astrocytoma and as a molecular marker for the prognosis.

Intramedullary thoracic spinal cord meningioma: a rare case report and review of the literature.

A 33-year-old male presented with a thoracic spinal intramedullary meningioma manifesting as bilateral asymmetric progressive weakness in the lower extremities. Preoperative magnetic resonance imaging (MRI) showed an intramedullary mass at the T1-T3 level. Intraoperative inspection found that the spinal cord was markedly swollen with a normal surface while dural attachment was not confirmed. Gross total removal of the tumor was achieved. The morphologic and immunohistochemical findings were compatible with the diagnosis of meningioma. Postoperatively, the patient recovered from preoperative paraplegia. Although extremely rare, meningiomas should be considered when diagnosing intramedullary tumors.

The expression of moesin in astrocytoma: correlation with pathologic grade and poor clinical outcome.

Moesin, a member of the ERM family, acts as a linker between the actin cytoskeleton and the plasma membrane and plays a key role in the control of cell morphology, motility, adhesion and other processes of tumourigenesis. The expression pattern and clinical significance of moesin in astrocytoma remain unknown. In this study, we used RT-PCR to systematically investigate the expression of moesin in 49 astrocytomas of different pathological grade and 6 normal brain tissues. We found that the mRNA expression levels of moesin in astrocytomas were significantly higher in comparison with normal brain tissues. Furthermore, moesin up-regulation was correlated with pathological grade of astrocytomas. Subsequently, we tested 112 astrocytomas and 14 normal brain tissues by immunohistochemistry. Similar results were also confirmed. Univariate and multivariate survival analysis were used to determine the correlations of moesin expression with overall survival and progression-free survival. Our results showed the expression of moesin was strongly negatively correlated with the patient progression-free survival and overall survival. These results suggest moesin protein involved in the genesis and progression of astrocytomas and might be regarded as an independent predictor of poor prognosis.

ALDH1 expression is correlated with pathologic grade and poor clinical outcome in patients with astrocytoma.

Aldehyde dehydrogenase 1 (ALDH1), a detoxifying enzyme, is a stem-like cell marker, but its expression pattern and clinical significance in astrocytoma remain unclear. In this study, we used immunohistochemical analysis to systematically investigate the expression of ALDH1 in 76 astrocytomas of different pathological grade and seven samples of normal brain tissues. We found that ALDH1 was expressed in some of the astrocytomas but was not detected in normal brain tissues. The proportion of ALDH1-expressing cells was positively correlated with the pathological grade of the astrocytomas, but not with patient age, sex or tumor size. We also collected detailed follow-up data and analyzed the correlation of ALDH1 expression with overall survival (OS) and progression-free survival (PFS) using univariate and multivariate analysis. We found that the proportion of ALDH1-positive cells was an independent prognostic factor for PFS and OS. These results show that ALDH1 is expressed in astrocytoma, and that its expression is correlated with pathological grade and patient survival.

Large medial sphenoid wing meningiomas: long-term outcome and correlation with tumor size after microsurgical treatment in 127 consecutive cases.

AIM: We present the long-term outcomes as well as their correlation with tumor size in 127 consecutive patients harboring large MSWM after microsurgical treatment. MATERIAL AND METHODS: The retrospective analysis of clinical data and follow-up data of 127 microsurgical treated patients with MSWM was performed. The mean maximum diameter of tumors was 5.2cm (ranged 1.5-10.0cm). RESULTS: 104 cases (81.9%) achieved gross total resection. There was no operative mortality. Detailed follow-up data was available in 120 cases for a mean duration of 81.6 months (12-216 months). The permanent morbidity was 14.2%. The mean KPS score 1 year after surgery was 90.6 (ranged 60-100). Among 74 patients of preoperative visual acuity (VA) impairment, postoperative VA improved in 42 cases (56.8%), unchanged in 30 (40.5%), and deteriorated in 2 (2.7%). MR images revealed tumor recurrence after total resection in 10 cases (10.2%) and tumor progression after subtotal resection in 10 cases (45.5%). CONCLUSION: Tumor recurrence was the major risk in the long run, thus the initial surgery was extremely important and hence should be aggressive. The size of tumor affected the extent of tumor removal determining clinical outcomes including VA improvement and KPS score immediately after surgery; however, it was not correlated with long-term overall outcomes.

[Facial nerve preservation following microsurgical removal of large and huge acoustic neuroma].

OBJECTIVES: To evaluate the long-term facial nerve function of patients following microsurgical removal of large and huge acoustic neuroma, and to identify the factors that influence these outcomes. METHODS: A retrospective review was performed which included 176 consecutive patients with a large acoustic neuroma (≥ 30 mm) underwent a retrosigmoid craniotomy for tumor resection between January 2002 to November 2009. House-Brackmann (HB) Scale was used preoperatively and in a long-term follow-up after surgery. Test for linear trend was applied for statistic analysis. RESULTS: Complete resection was achieved in 168 (95.5%) of these 176 patients with a mortality of 1.7%. Anatomic preservation of the facial nerve was attained in 96.0% of the patients. In the series of 96 patients who had at least 1-year follow-up (mean 3.0 years) the facial nerve function preservation (HB grade 1 - 2) was totally attained in 79 patients (82.3%), and 40 of 55 patients (72.7%) who presented huge tumors (diameter > 40 mm) among the 96 patients had facial nerve function preserved. Analysis showed that facial nerve function correlated linearly with tumor sizes (χ(2) = 14.114, ν = 1, P < 0.05). CONCLUSIONS: Complete removal of large and giant acoustic neuroma may be obtained via retrosigmoid approach with facial nerve preservation. Excellent long-term facial function can be expected in the majority of patients who undergo microsurgical removal of vestibular schwannoma via the suboccipital retrosigmoid approach. Tumor size is a significant prognostic parameter for facial nerve function following vestibular schwannoma surgery.

[Surgical outcomes of pediatric symptomatic epilepsy and their influencing factors].

OBJECTIVE: To investigate the surgical outcomes of pediatric symptomatic epilepsy and the influencing factors for postoperative outcomes. METHODS: A cohort of 48 children with symptomatic epilepsy received surgical treatment from October 2004 to September 2008. The surgical outcomes were followed up. RESULTS: A 27.3 months (range 12-51 months) follow-up was performed in 43 cases. Engel classification for evaluating postoperative epileptic outcomes showed that class I in 32 cases (74%), class II in 4 cases (9%), class III in 4 cases (9%) and class IV in 3 cases (7%). Preoperative seizure frequency is an independent predictor of postoperative epileptic outcomes (P<0.05). CONCLUSIONS: Operative treatment can lead to a favorable result in children with symptomatic epilepsy. Preoperative seizure frequency is an independent influencing factor for postoperative outcomes.

Expression and clinical significance of EGFL7 in malignant glioma.

PURPOSE: Tumor angiogenesis is an important factor for the continuous growth of human malignancies and can be used to predict the prognosis for patients. In the current study, we examined the expression of EGF-like domain 7 (EGFL7), an endothelial cell-derived secreted factor, in malignant gliomas and explored its clinical significance. METHODS: We determined the steady-state mRNA levels of EGFL7 from 36 fresh glioma samples by semi-quantitative RT-PCR and the protein levels from 45 paraffin-embedded glioma samples by immunohistochemistry, respectively. Normal brain tissues from 10 patients with brain trauma were used as control. We also analyzed the correlations between the expression levels of EGFL7 and various clinical parameters, including patient gender, age, tumor grade, tumor proliferation marker Ki-67, and microvessel density (MVD). RESULTS: We found that EGFL7 was not detectable in normal brain tissues, but was up-regulated in both tumor cells and vascular endothelial cells within malignant glioma. The expression level of EGFL7 in malignant glioma significantly correlated with the tumor grade, Ki-67 expression and MVD (P < 0.01). CONCLUSIONS: Our data suggest that EGFL7 expression is a novel predictive factor for the clinical progression of malignant glioma, and may constitute a therapeutic target for anti-angiogenesis therapy in patients with the disease.

[Surgical treatment of childhood craniopharyngioma: clinical analysis of 31 cases].

OBJECTIVE: To study the diagnosis, surgical treatment and outcome of craniopharyngioma in 31 children. METHODS: The clinical data of 31 children (aged 7-14 years) with craniopharyngioma were studied retrospectively. RESULTS: Headache, visual disorder and growth retardation were main manifestations in the 31 children. The 31 children were definitely diagnosed with craniopharyngioma by CT and MRI. In the 31 cases, 19 (61.3%) underwent total tumor removal, 5 (16.1%) subtotal removal, and 7 (22.6%) partial removal. After tumor removal, transient diabetes insipidus occurred in 19 cases (61.3%) and long-term diabetes insipidus in 3 cases. Six cases (19.4%) presented hypothalamic injuries after surgery. No patient died after surgery. Five patients (16.1%) had recurrent tumor in a mean follow-up of 32.5 months. CONCLUSIONS: The diagnosis of childhood craniopharyngioma may be based on clinical manifestations and CT/MRI examinations. Craniotomy is a preferred surgical treatment. Proper extent of tumor resection should be determined in order to reduce the tumor recurrence and the incidence of postoperative complications.