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Intrinsic third ventricular craniopharyngiomas (IVCs) are usually considered as a contraindication of endoscopic endonasal approach (EEA). The aim of this study is to evaluate the safety and feasibility of EEA for the resection of IVCs based on MRI topographical diagnosis and surgical findings. We reviewed the data of 22 patients who were diagnosed to be IVCs according to five MRI criteria and underwent surgery through EEA. Sixteen IVCs were resected using endoscopic endonasal infrachiasmatic corridor, five IVCs by using endoscopic endonasal suprachiasmatic trans-lamina terminalis corridor, and one IVC by using both the infrachiasmatic and suprachiasmatic corridors. During the operation, all the 22 cases were verified to be IVCs. Gross total resection was achieved in 21 (95.5%) patients. After surgery, visual improvement was observed in 14 (63.6%) patients, no change in 6 (27.3%) patients, and some deterioration in 2 (9.1%) patients. An improvement in intellectual ability was observed in nine (40.9%) patients, no change in twelve (54.5%) patients, and some deterioration in one (4.5%) patient. Fifteen of the 22 patients (68.2%) developed new endocrinological deficit. One postoperative cerebral spinal fluid leakage occurred. EEA can be used as a safe and efficacious approach for the radical resection of IVCs. The combination of the five MRI criteria may serve as an accurate preoperative diagnostic tool to define the topographical relationships between craniopharyngiomas and the third ventricle. The endoscopic transnasal view from below has the advantage of clarifying the relationship between tumors and the third ventricle floor.

Objective Skull base chordoma (SBC) is rare and one of the most challenging diseases to treat. We aimed to assess the optimal timing of adjuvant radiation therapy (RT) and to evaluate the factors that influence resection and long-term outcomes. Methods In total, 284 patients with 382 surgeries were enrolled in this retrospective study. Postsurgically, 64 patients underwent RT before recurrence (pre-recurrence RT), and 47 patients underwent RT after recurrence. During the first attempt to achieve gross-total resection (GTR), when the entire tumor was resected, 268 patients were treated with an endoscopic midline approach, and 16 patients were treated with microscopic lateral approaches. Factors associated with the success of GTR were identified using χ2 and logistic regression analyses. Risk factors associated with chordoma-specific survival (CSS) and progression-free survival (PFS) were evaluated with the Cox proportional hazards model. Results In total, 74.6% of tumors were marginally resected [GTR (40.1%), near-total resection (34.5%)]. History of surgery, large tumor volumes, and tumor locations in the lower clivus were associated with a lower GTR rate. The mean follow-up period was 43.9 months. At the last follow-up, 181 (63.7%) patients were alive. RT history, histologic subtype (dedifferentiated and sarcomatoid), non-GTR, no postsurgical RT, and the presence of metastasis were associated with poorer CSS. Patients with pre-recurrence RT had the longest PFS and CSS, while patients without postsurgical RT had the worst outcome. Conclusion GTR is the goal of initial surgical treatment. Pre-recurrence RT would improve outcome regardless of GTR.

This study explored the function of microRNAs (miRNAs) in invasive pituitary adenomas (IPA), and developed a microRNA-exosome strategy for the disease treatment. Differentially expressed miRNAs and tumor-associated markers in IPA, non-invasive pituitary adenoma (NIPA), and rat pituitary adenoma cells were identified by bioinformatics analysis and qRT-PCR. Then, the cells were treated by miR-149-5p and miR-99a-3p mimics or inhibitors, or incubated with modified exosome with overexpressed or silenced miRNAs. The cell behaviors were analyzed by molecular experiments. Xenograft assays were constructed by injection of pituitary adenoma cells and exosome into NU/NU nude mice. Tumor size, weight, and expressions of markers related to miRNAs and angiogenesis were determined. Target genes for miR-99a-3p and miR-149 were predicted and verified by bioinformatics analysis and molecular experiments. Twenty differentially expressed miRNAs were identified, among which miR-99a-3p and miR-149 were inhibited in both pituitary adenoma cells and tissues significantly. Expressions of E-cadherin and p53 were down-regulated, while those of MMP-2, MMP-9, N-cadherin, Vimentin, and VEGF were up-regulated in pituitary adenoma cells and tissues, especially in IPA. Further experiments revealed that overexpressed miR-149 and miR-99a-3p inhibited the growth and metastasis of pituitary adenoma cells and tube formation of endothelial cells. MiR-149 and miR-99a-3p overexpressed by exosome showed similar suppressive effects on cell viability, metastasis, tube formation ability, in vivo tumor growth, and expressions of angiogenesis-related markers. Further analysis showed that NOVA1, DTL, and RAB27B were targeted by miR-99a-3p. This study found that overexpressed miR-149-5p and miR-99a-3p induced by exosome could suppress the progression of IPA. 1. MiR-149-5p and miR-99a-3p affect the expression of EMT- and ECM-related markers and tumor-related genes in rat pituitary adenoma cells treated with exosomes. 2. Exosome inhibited the tumor growth. 3. Overexpressed miR-149-5p and miR-99a-3p induced by exosome.

Background Dysregulated lncRNA PCAT6 was discovered in many cancers excluding pituitary adenomas (PA). Therefore, we explored the role of PCAT6 in PA in this research. Methods Abnormally expressed miRNAs were analyzed by bioinformatics and RT-qPCR. The target and regulator of miR-139-3p were determined by bioinformatics, dual-luciferase reporter assay, or RIP. The correlation among PCAT6, miR-139-3p, and BRD4 was further analyzed. The viability, apoptosis, cell cycle distribution of PA cells, as well as their ability to invade, migrate, and proliferate, were tested after transfection through CCK-8, flow cytometry, transwell, wound healing, and colony formation assays. After construction of transplanted-tumor model in nude mice, cell apoptosis in the tumor was detected by TUNEL. The expressions of PCAT6, BRD4, miR-139-3p, and apoptosis-related factors in PA tissues, cells, or tumor tissues were detected by RT-qPCR, Western blot, or IHC. Results PCAT6 and BRD4 were high-expressed but miR-139-3p was low-expressed in PA. Both the 3′-untranslated regions of PCAT6 and BRD4 mRNAs were demonstrated to contain a potential binding site for miR-139-3p. PCAT6 was positively correlated to BRD4, and miR-139-3p was negatively correlated to PCAT6 and BRD4. MiR-139-3p mimic, shPCAT6 and siBRD4 inhibited the viability, migration, invasion, and proliferation of PA cells while inducing apoptosis. MiR-139-3p mimic and shPCAT6 inhibited the cell cycle progression of PA cells, decreased the weight and volume of the xenotransplanted tumor, and reduced the levels of Bcl-2 and BRD4 while enhancing the levels of Bax, miR-139-3p, and Cleaved caspase-3. MiR-139-3p inhibitor caused the opposite effect of miR-139-3p mimic and further reversed the effect of shPCAT6 on on PA cells. Conclusion PCAT6 regulated the progression of PA via modulating the miR-139-3p/BRD4 axis, which might provide a novel biomarker for the prevention, diagnosis, and treatment of PA.

Background Increasing studies have demonstrated that activated platelets play an essential role in tumour progression. However, the level and prognostic role of platelet indices in chordoma patients remain unclear. The aim of the current study was to characterize the prognostic performance of platelet count (PLT), mean platelet volume (MPV) and platelet distribution width (PDW) in skull base chordoma patients. Methods 187 primary skull base chordoma patients between January 2008 and September 2014 were enrolled in this retrospective study. The optimal cut-off values were determined by X-tile software, and the correlations between PLT, MPV, PDW and clinicopathological features were further analysed. Kaplan-Meier curve and Cox regression analysis were used for survival analysis. Results The values of preoperative PTL, MPV and PDW ranged from 104 to 501 × 109/L, 6.7 to 14.2 fl, and 7.8 to 26.2%, respectively. Elevated PLT was associated with larger tumour volume (p = 0.002). Kaplan-Meier survival analysis revealed that increased MPV and PDW were associated with shorter overall survival (p = 0.022 and 0.008, respectively). Importantly, multivariate Cox analysis demonstrated that elevated PDW was an independent unfavourable predictive factor for overall survival (hazard ratio (HR), 2.154, 95% confidence interval (CI), 1.258–3.688, p = 0.005). Conclusions Our data show that elevated MPV and PDW are associated with poor outcomes in skull base chordoma and that PDW may be helpful to identify patients with high risk.

The current study aimed to characterize SNF5 expression and investigate the relationship between SNF5 and clinicopathological features in skull base chordoma. 48 patients diagnosed with skull base chordoma were enrolled in this study. Tissue microarray and immunohistochemistry were performed to evaluate the expression of SNF5 in skull base chordoma. Kaplan–Meier survival analysis was used to assess survival. Multivariable Cox regression analysis was used to identify risk factors affecting patient survival. The H-scores for cytoplasmic SNF5 ranged from 124.47 to 254.52. Low expression of SNF5 was correlated with shorter overall survival (OS) (p = 0.021). Patients with age > 55 years old had shorter progression free survival (PFS) and OS times than patients whose age ≤ 55 years old (p = 0.005 and 0.003, respectively). The gross total resection group showed longer PFS than the non-gross total resection group (p = 0.024). Females showed shorter PFS times than males (p = 0.033). Multivariable Cox regression analysis showed that age, extent of resection and sex were independent prognostic factors for PFS (p = 0.010, 0.013 and 0.042, respectively). Age was an independent prognostic factor for OS (p = 0.010). Our study indicate that low expression of SNF5 is associated with poor prognosis in skull base chordoma.

The correlation between hydrocephalus and Chiari type I malformation (CIM) has been debated since Chiari's first descriptions of CIM but some studies have shown that CIM and hydrocephalus (HCP) could cause symptoms/disease of each other or vice versa. Recent research has found that treatment focused on hydrocephalus with ventricle enlargement also provides alleviation of CIM and even of syringomyelia. However, the lack of consensus among previous studies left unanswered the question of how endoscopic third ventriculostomy (ETV) addresses CIM and why it fails. Ten symptomatic hydrocephalic patients associated with CIM underwent ETV from October 2002 to May 2012. The clinical features and neuroimaging of all patients were reviewed. Statistical analysis was applied to evaluate the changes in the tonsillar ectopia and the ventricle dilation after operation. The mean follow-up period of this series was 92 months (range 24-163 months). Eight patients (80%) remained shunt free or experienced symptom relief following ETV. The remaining two patients were identified as failures due to the deterioration of symptoms or subsequent hindbrain decompression. Endoscopic third ventriculostomy provides an effective treatment for hydrocephalus associated with CIM, which can relieve HCP and improve the symptoms of CIM in most patients. The clinical outcomes are related to the major cause of the tonsillar herniation.

Background To investigate the relationship between cyclin B1 (CCNB1) gene expression and cavernous sinus invasion in pituitary adenomas. Methods Twenty-four pituitary adenoma tissue samples were examined by RT-qPCR and Western blot to assess the mRNA expression levels and protein levels of CCNB1, E-cadherin and N-cadherin. Correlation analyses between the expression levels of E-cadherin, N-cadherin and CCNB1 were performed. After lentivirus-mediated knockdown of CCNB1 in rat pituitary adenoma cell lines (GH3 and GT1-1), cell function changes were studied. The relationship between CCNB1 and epithelial-mesenchymal transition (EMT) was further verified by animal experiments. Results CCNB1 and N-cadherin gene expression were significantly higher in the invasive pituitary adenomas than in the non-invasive pituitary adenomas. Conversely, E-cadherin expression in the invasive pituitary adenomas was significantly lower. CCNB1 gene expression was downregulated in the GH3 and GT1-1 pituitary adenoma cell lines; N-cadherin expression was also decreased, but E-cadherin expression was increased. These results were confirmed in vivo. After downregulation of CCNB1, cell invasion and migration was significantly reduced in Transwell experiments. Conclusion High CCNB1 expression in pituitary adenoma affects cavernous sinus invasion through EMT.

The aim of this study is to retrospectively analyze 161 cases of surgically treated skull base chordoma, so as to summarize the clinical classification of this tumor and the surgical approaches for its treatment via transnasal endoscopic surgery. Between August 2007 and October 2013, a total of 161 patients (92 males and 69 females) undergoing surgical treatment of skull base chordoma were evaluated with regard to the clinical classification, surgical approach, and surgical efficacy. The tumor was located in the midline region of the skull base in 134 cases, and in the midline and paramedian regions in 27 cases (extensive type). Resection was performed via the transnasal endoscopic approach in 124 cases (77%), via the open cranial base approach in 11 cases (6.8%), and via staged resection combined with the transnasal endoscopic approach and open cranial base approach in 26 cases (16.2%). Total resection was achieved in 38 cases (23.6%); subtotal resection, 86 cases (53.4%); partial resection of 80-95%, 29 cases (18%); and partial resection

To investigate the clinical and angiographic outcomes of spontaneous symptomatic large or giant vertebrobasilar dissecting aneurysms (VBDAs) following reconstructive endovascular treatment (EVT) with stent(s).We retrospectively identified 21 patients with spontaneous symptomatic large or giant VBDAs who had been treated with reconstructive EVT between September 2009 and September 2013 in our department. There were 20 men and 1 woman, with a mean age of 46.5 years (range: 17-67 years). Clinical and angiographic data were reviewed and evaluated.Reconstructive EVT with sole stenting (SS, 10 cases) or stent-assisted coiling (SAC, 11 cases) technique was technically feasible in all cases. Angiographic follow-up results confirmed delayed thrombosis of the aneurysm sac in only two of the eight cases after SS, and recurrence of the aneurysm sac in six of the nine cases after SAC. Postoperative complications or poor neurologic outcomes occurred in seven cases (33.3 %). Three patients died after SS, including postoperative subarachnoid hemorrhage in one case and pulmonary embolism in one case. The other patient died soon after SAC, without radiologic result to confirm the causes of death. Other adverse events after treatment include ischemic complication in two cases, intramural hemorrhage in one case, aggravation of initial mass effect in one case. As to the other 14 cases, the post-procedural processes were uneventful and no complication was observed. The condition of them was improved in seven cases (33.3 %), and unchanged in seven cases (33.3 %) during follow-up.Reconstructive EVT with traditional intracranial stent(s) for the treatment of large and giant VBDAs carries a high failure rate and substantial risk of complications. The outcome of treating these difficult lesions with traditional intracranial stenting seems questionable and unpredictable.

The purpose of this study was to evaluate the effectiveness and safety as well as the clinical and angiographic results of endovascular treatment (EVT) for patients with hemorrhagic dural arteriovenous fistulas (DAVFs). From April 2009 to November 2013, 46 consecutive patients (7 women, 39 men; mean age, 46.7 years) diagnosed with hemorrhagic intracranial DAVFs at our department were enrolled in this study. Clinical and angiographic data were reviewed and evaluated. Two fistulas were cured by transvenous approach, and all other fistulas were embolized through transarterial route. After treatment with last embolization, a residual shunt was observed in 15 patients, including near-total obliteration of the fistula in 6 patients (13.0 %) and partial obliteration of the fistula in 9 patients (19.6 %). Seven of them underwent supplementary Gamma knife surgery. Complications occurred during or after EVT in six patients. One patient died 10 days after EVT because of complications of Onyx embolus into the posterior inferior cerebellar artery. Other complications included microcatheter entrapment in one case, trigeminocardiac reflex in one, facial nerve paresis in two, and occulomotor nerve paresis in one. The facial nerve paresis in one patient markedly improved but did not completely resolve during follow-up period. The other four patients recovered well, without symptoms at clinical follow-up. Angiographic follow-up result was obtained in 35 cases, with complete obliteration in 27 of them (77.1 %). Clinical follow-up outcomes were good, with 38 patients (82.6 %) reporting modified Rankin Scale of either 0 or 1. No patient suffered recurrent intracranial hemorrhage during follow-up. EVT was effective and safe in the modern management of ruptured intracranial DAVFs, with complete cure in most lesions. Clinical outcomes were good despite patients presenting with intracranial hemorrhage.

Evidences have showed that the deprivation of vision can considerably alter the resting-state activity both within and beyond the visual cortices. However, the functional changes of the brain cortices related to partially vision-deprivation are still largely unknown. Using resting-state functional MR imaging, we quantitatively evaluated the regional homogeneity(ReHo) and functional connectivity(FC) changes between 25 pituitary adenoma patients with visual impairment and 25 healthy controls(HCs). Compared with HCs, PAs exhibited significant increased ReHo in the left superior occipital gyrus, bilateral middle occipital gyrus and reduced ReHo in the left inferior frontal gyrus and right middle temporal gyrus. PAs also showed decreased FC between vision-related area and higher-order cognitive brain areas. Furthermore, we identified that in the PAs group the FC between the left V1 and left V3 increased while the FC between left V2v and left V5 significantly decreased, the FC between left V4 area and the V3, V2d area increased. In our study, we identified that the ReHo and FC were altered between the vision-related cortices and other higher-order cognitive cortices along with disorganized functional connectivity within the visual system in PAs with visual impairment. These findings may provide important insights to understand the plasticity of visual network.

It is becoming evident that long non-coding RNAs (lncRNAs) participate in diverse biological processes via distinct mechanisms. Many lncRNAs have altered expression and likely to have functional roles in tumorigenesis. Although loss of maternally-expressed gene 3 (MEG3) expression has been detected in non-functioning pituitary adenomas (NFPAs), there are no published reports regarding the association between MEG3 expression and the invasive ability of NFPAs. Moreover, the roles of Hox transcript antisense intergenic RNA (HOTAIR) and metastasis-associated lung adenocarcinoma transcript 1 (MALAT-1) in NFPAs have not been examined. To investigate the role of MEG3, HOTAIR, and MALAT-1 in NFPA development and invasion. MEG3, HOTAIR, MALAT-1 and proliferating cell nuclear antigen (PCNA) were detected in 52 NFPA samples and seven normal human anterior pituitaries using real-time quantitative reverse transcription polymerase chain reaction. MEG3 lncRNA levels gradually decreased whereas HOTAIR lncRNA levels gradually increased from normal anterior pituitaries to non-invasive NFPAs to invasive NFPAs. There was a significant association between MEG3 (P

Prolactinomas, or prolactin-secreting adenomas, constitute the most common type of hyperfunctioning pituitary adenoma. Dopamine agonists are used as first-line medication for prolactinomas, but the tumors are resistant to the therapy in 5-18 % of patients. To explore potential mechanisms of resistance to bromocriptine (a dopamine agonist), we analyzed six responsive prolactinomas and six resistant prolactinomas by whole-exome sequencing. We identified ten genes with sequence variants that were differentially found in the two groups of tumors. The expression of these genes was then quantified by real-time reverse-transcription PCR (RT-qPCR) in the 12 prolactinomas and in six normal pituitary glands. The mRNA levels of one of the genes, PRB3, were about fourfold lower in resistant prolactinomas than in the responsive tumors (p = 0.02). Furthermore, low PRB3 expression was also associated with tumor recurrence. Our results suggest that low levels of PRB3 mRNA may have a role in dopamine-agonist resistance and tumor recurrence of prolactinomas.

The aim of this study was to investigate the endoscopic treatment of cerebral hemisphere convexity arachnoid cyst. Eight cases of hemisphere convexity arachnoid cyst treated with cyst–ventricular or cisternal endoscopic approach in September 2007 to March 2011 were retrospectively recruited. The clinical symptoms, radiological findings, surgical indications, surgical approach, complications, and follow-up studies were analyzed. All patients showed convexity arachnoid cysts adjacent to the ventricles or cisternal. After treatment, all patients showed decrease in size of the cysts (100 %), with preoperative symptoms disappeared in six patients and improved in two cases. In one case, postoperative subdural effusion was found without symptoms reported. Endoscopic surgery is ideal for treatment of arachnoid cysts adjacent to the ventricles or cisternal.

Background The aim of this study was to assess the effectiveness of neuroendoscopy compared with non-neuroendoscopic procedures for treating patients with arachnoid membrane cysts in the lateral ventricles. Methods The medical records of 28 patients with arachnoid membrane cysts in the lateral ventricles who were treated with neuroendoscopy and 39 such patients treated with non-neuroendoscopic techniques using classic treatment procedures were reviewed. The neuroendoscopic approach combined craniotomy, corticectomy, lesion resection and cyst ventriculostomy or cyst cisternostomy to restore normal cerebrospinal fluid circulation. The non-neuroendoscopic techniques included craniotomy, corticectomy, and lesion resection performed under a microscope. Clinical outcomes of symptoms and cyst size change on imaging were compared between the two treatment groups during follow-up (range: 1–5 years). Results Patients in the neuroendoscopy group had significantly less blood loss (P P P = 0.011) compared with the patients in the non-neuroendoscopy group. In the neuroendoscopy group there was no cyst recurrence whereas in the non-neuroendoscopy group 8 (20.5%) patients had cyst recurrence. However, all patients in the neuroendoscopy group had postoperative transient fever and 8 (28.6%) patients had subdural fluid accumulation which was treated and subsequently resolved during follow-up. These symptoms did not occur in the non-neuroendoscopy group. Conclusion We found that neuroendoscopic therapy for arachnoid cysts in the lateral ventricles was more efficacious than non-neuroendoscopic methods. Our results indicate that neuroendoscopy may produce better clinical outcomes than non-neuroendoscopic procedures in treating patients with arachnoid cysts in the lateral ventricles.