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  • Author or Editor: Zhen Wu x
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Sha Zhao, Zhen Liu, Zihan Yu, Xinran Wu, Rui Li and Xiaobo Tang

OBJECTIVE

Inflammation plays a key role in secondary brain damage following intracerebral hemorrhage (ICH). Glycogen synthase kinase–3β (GSK-3β) plays a strong proinflammatory role in many CNS diseases, including stroke. The present study was undertaken to examine the effects of 6-bromoindirubin-3ʹ-oxime (BIO), a specific inhibitor of GSK-3β, on inflammation in ICH rats.

METHODS

An ICH rat model was induced by autologous whole-blood injection into the striatum. First, 10, 20, 40, 60, 80, or 100 μg/kg BIO was applied to ICH animals to determine an optimal dosage for producing sufficient GSK-3β inhibition in rat ipsilateral hippocampus by Western blotting. Second, 40 μg/kg BIO was applied to ICH rats for 1, 3, 7, or 14 days, respectively, to determine a suitable intervention time course of BIO by Western blotting analysis on GSK-3β. Third, Western blotting and enzyme-linked immunosorbent assay were used for quantification of inflammation-related factors upstream or downstream of GSK-3β in rat ipsilateral hippocampus. Then, immunohistochemical staining was applied to detect activated microglia and apoptotic cells in rat ipsilateral hippocampus. Last, neurobehavioral tests were performed to assess the sensorimotor impairments in the ICH rats.

RESULTS

The results show that BIO 1) blocked GSK-3βTyr216 phosphorylation/activation, thus stabilizing β-catenin, increasing upstream brain-derived neurotrophic factor and downstream heat shock protein 70 levels, and decreasing the levels of nuclear factor–κB p65 and cyclooxygenase 2; 2) decreased the levels of the proinflammatory cytokines tumor necrosis factor–α and interleukin (IL)–1β and IL-6 and elevated the level of antiinflammatory cytokine IL-10; 3) inhibited microglia activation and cell apoptosis; and 4) improved the sensorimotor deficits of ICH rats.

CONCLUSIONS

BIO posttreatment inhibited microglia activation, prevented inflammation and hippocampal cell death, and ameliorated functional and morphological outcomes in a rat ICH model through inactivation of GSK-3β.

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Da Li, Shu-Yu Hao, Zhen Wu, Li-Wei Zhang and Jun-Ting Zhang

Medulla oblongata teratomas are rare. The authors report 2 new cases of teratomas that occurred exclusively in the medulla oblongata. The first case was in a 9-year-old boy who presented with a 6-month history of neck pain and repeated paroxysmal vomiting. Based on preoperative radiographic findings, the initial diagnosis was of an intraaxial medulla oblongata hemangioblastoma. Intraoperatively, the cystic component of the tumor was gray, gelatinous, and soft in consistency. The solid component was light pink, rubbery, and nodular in appearance, with an identifiable boundary. The lesion was completely removed. Histopathological investigation revealed a mature teratoma. Postoperatively, the patient was supported with ventilator assistance and received a tracheotomy, but died of intracranial infection. The second case was in a 10-year-old boy with intermittent headache for 1 month. Radiographs revealed an exophytic cystic and solid lesion with dorsal involvement of the medulla oblongata. The lesion was predominantly solid, pinkish gray, tenacious, and moderately vascularized, with clearly delineated surgical dissection planes. The histopathological examination confirmed a diagnosis of immature teratoma. Total resection was achieved, followed by postoperative chemotherapy. He was alive without recurrence of the lesion or symptoms at 59 months after surgery.

Resection of medulla oblongata teratoma is challenging, with inherent surgical risks that are contingent on the tumor growth pattern. Teratomas should be considered in the differential diagnosis of brainstem lesions. Chemotherapy has been suggested for immature teratomas. Long-term follow-up and larger studies of teratomas in unusual locations are required to improve practitioners' understanding of this disease's treatment and outcomes.

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Cheng-Bei Li, Lai-Rong Song, Da Li, Jian-Cong Weng, Li-Wei Zhang, Jun-Ting Zhang and Zhen Wu

OBJECTIVE

The overall survival and pertinent adverse factors for primary intracranial malignant melanoma (PIMM) have not been previously determined. This aim of this study was to determine the rates of progression-free survival (PFS) and overall survival (OS) and identify the adverse factors for PIMM.

METHODS

This study included 15 cases from the authors’ own series and 100 cases with detailed clinical data that were obtained from the literature from 1914 to 2018 using the Ovid Medline, EMBASE, PubMed, Cochrane, and EBSCO databases. Patient demographics, treatment (surgery, chemotherapy, and radiotherapy [RT]), PFS, and OS were reviewed. Data from prior publications were processed and used according to PRISMA guidelines.

RESULTS

Diffuse lesions were identified in 24 (20.9%) patients, who had a younger age (p < 0.001). The mean follow-up time was 16.6 months, and 76 (66.1%) deaths occurred. The 6-month, 1-year, 3-year, and 5-year OS rates of the whole cohort were 62.8%, 49.9%, 28.9%, and 17.2%, respectively, with an estimated median survival time (EMST) of 12.0 months. The multivariate analysis revealed that gross-total resection (GTR) (HR 0.299, 95% CI 0.180–0.497, p < 0.001), radiotherapy (HR 0.577, 95% CI 0.359–0.929, p = 0.024), and chemotherapy (HR 0.420, 95% CI 0.240–0.735, p = 0.002) predicted a better OS. The EMST was 5.0 months in patients with diffuse-type PIMM and 13.0 months in patients with the solitary type. Patients receiving GTR with adjuvant RT and/or chemotherapy (GTR + [RT and/or chemo]) had significantly higher 1-year and 5-year OS rates (73.0% and 40.1%, respectively) and a longer EMST (53 months) than patients who underwent GTR alone (20.5 months) or RT and/or chemotherapy without GTR (13.0 months).

CONCLUSIONS

Optimal outcomes could be achieved by radical resection plus postoperative radiotherapy and/or chemotherapy. Patients with diffuse PIMM have a more severe clinical spectrum and poorer survival than patients with solitary PIMM. Immunotherapy and targeted therapy show promise as treatment options for PIMM based on results in patients with brain metastases from extracranial melanoma.

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Da Li, Shu-Yu Hao, Gui-Jun Jia, Zhen Wu, Li-Wei Zhang and Jun-Ting Zhang

Object

Cerebral cavernous malformations have been studied widely, but the natural history of brainstem cavernous malformations (CMs) is not well defined, and hemorrhages caused by brainstem CMs are devastating. The goal of this study was to quantify the hemorrhage risks and functional outcomes of patients with brainstem CMs.

Methods

This prospective, longitudinal, cohort study included patients with brainstem CMs diagnosed between 1985 and 2012. The clinical courses of all patients were recorded. Predictors of hemorrhage and the overall untreated outcomes were evaluated.

Results

A total of 331 patients (46.5% female) were included, with a mean follow-up duration of 6.5 years. The annual hemorrhage rates in patients initially presenting with hemorrhage with (n = 215) or without (n = 34) focal neurological deficits were 15.9% and 12.4%, respectively. However, the annual hemorrhage rate was 8.7% in patients initially presenting without hemorrhage (n = 82). The risk factors for hemorrhage were female sex (hazard ratio [HR] 1.445, p = 0.041), prior hemorrhage (HR 1.277, p = 0.029), and perilesional edema (HR 1.830, p = 0.002). Overall, neurological function at the most recent assessment was improved compared with neurological function at diagnosis. Additionally, 307 patients (92.7%) improved or stabilized, 268 (81.0%) lived independently, and 95 (28.7%) completely recovered. Predictors favoring complete recovery were no prospective hemorrhage (HR 1.958, p = 0.001), younger age (HR 1.268, p = 0.001), and small lesion size (HR 1.578, p = 0.004).

Conclusions

Patients' initial presentation predicts their prospective annual hemorrhage rate. This study suggests that several strong risk factors for hemorrhage and predictors of brainstem CM outcomes may enable clinicians to evaluate the potential hemorrhage risks of their patients and design personalized treatments.

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Xinru Xiao, Zhen Wu, Liwei Zhang, Guijun Jia, Jie Tang, Guolu Meng and Junting Zhang

Object

In this paper the authors describe a modified far-lateral transcondylar approach to remove hypoglossal neurilemmomas (HGNs).

Methods

Between September 2008 and June 2011, 11 consecutive patients with HGNs underwent tumor removal via a modified far-lateral transcondylar approach. The average age at presentation, tumor characteristics, cranial nerve (CN) deficits, and outcomes were assessed. The modified far-lateral transcondylar approach comprises several important steps. The first step is to remove the limited posterior aspect of the condylar facet to open the hypoglossal canal. The second step is to expose the posterior arch and the transverse process of C-1. A fat layer covers the venous plexus of the vertebral artery, and careful dissection along this surface of the fat layer is important to protect the vertebral artery from damage. The neck muscles are dissected caudally to expose the extracranial component of the tumor, which is located in front of the transverse process of C-1.

Results

Eleven cases of HGNs were treated during the study period. The mean patient age was 47.4 ± 8.9 years (range 31–59 years); there were 3 men and 8 women. The mean follow-up period was 14.1 ± 9 months. All patients presented with hypoglossal nerve deficits; other commonly observed deficits included glossopharyngeal and vestibular/cochlear nerve deficits. Gross-total resection of the tumor was achieved in 10 patients. A subtotal resection of the tumor was achieved in the remaining patient. Two patients had transient postoperative facial nerve palsies, 1 patient developed a new CN XI palsy postoperatively, and 5 patients experienced transient hoarseness and difficulty swallowing. Two patients required a tracheotomy because they demonstrated dysfunction of the caudal CNs and subsequently developed postoperative pneumonia. Postoperatively, 5 patients required the temporary placement of a nasogastric feeding tube. There were no surgery-related deaths in this series.

Conclusions

The modified far-lateral transcondylar approach is an effective treatment for HGNs, yielding a high total tumor removal rate with an acceptable rate of morbidity.

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Ming-Xiang Zou, Guo-Hua Lv, Xiao-Bin Wang and Jing Li

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Junpeng Ma, Kaibing Tian, Jiang Du, Zhen Wu, Liang Wang and Junting Zhang

OBJECTIVE

The object of this study was to clarify the expression characteristics and prognostic value of survivin in skull base chordomas.

METHODS

In this retrospective study, the authors measured the expression of survivin at the mRNA level in 81 samples from 71 patients diagnosed with skull base chordomas at their hospital in the period from July 2005 to January 2015. Clinical data collection, follow-up, and survival analyses were performed, and correlations were analyzed.

RESULTS

Of the 71 patients, 50 had primary chordomas with a mean survivin expression level of 1.09; the other 21 patients had recurrent chordomas with a mean survivin expression level of 2.57, which was 2.36 times higher than the level in the primary chordoma patients (p < 0.001, Mann-Whitney U-test). In addition, an analysis of 18 paired samples derived from 9 patients showed that the expression level of survivin was 2.62 times higher in recurrent tumors than in primary tumors (p = 0.002, paired t-test). The Spearman rank correlation coefficient method showed that the expression level of survivin was positively correlated with the mean ratio of tumor signal intensity to the signal intensity of surrounding brainstem on T1-weighted sequences (RT1; rs = 0.274, p = 0.021) and was negatively correlated with the mean ratio of tumor signal intensity to the signal intensity of surrounding brainstem on T2-weighted sequences (RT2; rs = −0.389, p = 0.001). A multivariate Cox proportional-hazards model suggested that pathology (p = 0.041), survivin expression level (p = 0.018), preoperative Karnofsky Performance Status (KPS; p = 0.012), and treatment history (p = 0.009) were independent prognostic factors for tumor progression. Survivin expression level (p = 0.008), preoperative KPS (p = 0.019), tumor diameter (p = 0.027), and intraoperative blood loss (p = 0.015) were independent prognostic factors for death.

CONCLUSIONS

Survivin expression level and preoperative KPS were independent significant prognostic factors for tumor progression and death in skull base chordoma patients. Recurrent skull base chordomas and chordomas with high RT1 and low RT2 were likely to have high survivin expression. Other independent risk factors related to tumor progression included conventional pathology and treatment history, whereas additional mortality-related risk factors included larger tumor diameter and greater intraoperative blood loss.

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Jing-Jie Zheng, Gui-Jun Zhang, Xu-Lei Huo, Liang Wang, Shu-Yu Hao, Li-Wei Zhang, Zhen Wu, Yu-Mei Wu, Jun-Ting Zhang and Da Li

OBJECTIVE

Primary intracranial rhabdomyosarcoma (PIRMS) is rare, and the effects of the treatment strategy on overall survival (OS) are unclear. This study aimed to evaluate risk factors pertinent to OS and to propose an optimal treatment strategy.

METHODS

Clinical data of patients with PIRMS treated at Beijing Tiantan Hospital and from the English-language literature between 1946 and 2018 were reviewed. A literature review was performed via Ovid, MEDLINE, Embase, PubMed, Web of Science, and Cochrane databases using the terms “rhabdomyosarcoma,” “intracranial,” “cerebral,” and “brain.” Previously published data were processed and used according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.

RESULTS

There were 8 males (66.7%) and 4 females with PIRMS at our institution, with a mean age of 24.3 years. Gross-total resection was achieved in 4 patients (33.3%), and adjuvant radiation and chemotherapy were administered in 5 (45.5%) and 3 (27.3%) patients, respectively. After a mean follow-up period of 13.7 months, all patients developed local-regional recurrence and died of the disease. Twenty-nine cases (14 female and 15 male) were reported in the literature with a median age of 9.0 years. After a mean follow-up duration of 18.6 months, 13 patients (44.8%) developed recurrences, 7 patients (24.1%) had extracranial metastasis, and 14 patients (48.3%) died. In the pooled cases, adjuvant radiation (hazard ratio [HR] 0.089, 95% confidence interval [CI] 0.027–0.288, p < 0.001) and age < 10 years (HR 0.227, 95% CI 0.077–0.666, p = 0.007) were independent predictors of good local-regional progression-free survival (LR-PFS). Adjuvant radiation therapy (HR 0.301, 95% CI 0.110–0.828, p = 0.020) and age < 10 years (HR 0.359, 95% CI 0.131–0.983, p = 0.046) were significant predictors for favorable OS in the multivariate model.

CONCLUSIONS

Due to the rarity of the disease, a poor outcome of PIRMS was demonstrated based on the pooled cohort. Use of radiation was associated with improved outcomes and should be considered to improve OS/LR-PFS. Further study is required to identify the optimal treatment regimen.

Systematic review no.: CRD42019121249 (crd.york.ac.uk/PROSPERO/)

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Da Li, Yang Yang, Shu-Yu Hao, Liang Wang, Jie Tang, Xin-Ru Xiao, Hui Zhou, Gui-Jun Jia, Zhen Wu, Li-Wei Zhang and Jun-Ting Zhang

Object

The aim of this study was to evaluate the pre- and postoperative rehemorrhage risk, neurological function outcome, and prognostic factors of surgically treated brainstem cavernous malformations (CMs) with long-term follow-up.

Methods

The authors conducted a retrospective review of the clinical data from 242 patients with brainstem CMs that were surgically treated between 1999 and 2010. Patient charts, imaging findings, and outcomes were examined.

Results

The study included 242 patients, with a male-to-female ratio of 1.3 and mean age of 32.6 years. The mean modified Rankin Scale scores on admission, at discharge, at 3 and 6 months after surgery, and at recent evaluation were 2.2, 2.6, 2.3, 1.8, and 1.5, respectively. The preoperative calculated annual hemorrhage and rehemorrhage rates were 5.0% and 60.9%, respectively. The complete resection rate was 95%. Surgical morbidity occurred in 112 patients (46.3%). Eighty-five patients (35.1%) demonstrated worsened condition immediately after surgery; 34 (41.0%) and 51 (61.4%) of these patients recovered to their baseline level within 3 and 6 months after surgery, respectively. At a mean follow-up of 89.4 months, the patients' condition had improved in 147 cases (60.7%), was unchanged in 70 cases (28.9%), and had worsened in 25 cases (10.3%). A total of 8 hemorrhages occurred in 6 patients, and the postoperative annual hemorrhage rate was 0.4%. Permanent morbidity remained in 65 patients (26.9%). The adverse factors for preoperative rehemorrhage were age ≥ 50 years, size ≥ 2 cm, and perilesional edema. The risk factors for postoperative hemorrhage were developmental venous anomaly and incomplete resection. The independent adverse factors for long-term outcome were increased age, multiple hemorrhages, ventral-seated lesions, and poor preoperative status. Favorable, complete improvement in the postoperative deficits over time was correlated with good preoperative neurological function and continuing improvement thereafter.

Conclusions

Favorable long-term outcomes and significantly low postoperative annual hemorrhage rates were achieved via surgery. Total resection should be attempted with an aim of minimal injury to neurological function; however, postoperative deficits can improve during the postoperative course. Close follow-up with radiological examination is proposed for patients with adverse factors predictive of rehemorrhage.

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Da Li, Shu-Yu Hao, Liang Wang, Gui-Lin Li, Jun-Mei Wang, Zhen Wu, Li-Wei Zhang, Jun-Ting Zhang and Wang Jia

OBJECTIVE

Medulloepithelioma (MEPL) is a rare, malignant primitive neuroectodermal tumor with dismal survival rates. The authors aimed to define independent risk factors for progression-free survival (PFS) and overall survival (OS) and to propose an optimal treatment protocol for MEPL.

METHODS

The authors reviewed the clinicoradiological data obtained in 12 patients with MEPL who underwent surgical treatment at their institution between January 2008 and June 2016. In addition, they reviewed 55 cases of MEPL published in the literature from January 1957 to July 2017. A pooled analysis of individual patient data of these 67 patients was performed to evaluate risk factors.

RESULTS

The authors’ cohort included 5 males and 7 females with a mean age of 15.7 years. Gross-total resection (GTR) was achieved in 10 (83.3%) patients. Radiotherapy (mean total dose 42.8 Gy) and chemotherapy were administered to 7 and 4 patients, respectively. After a median follow-up of 21.7 months, 6 (50%) patients suffered recurrence and subsequently died, with median PFS and OS times of 5.5 and 13.9 months, respectively. Among the 55 patients in the literature, 13 (23.6%) patients received GTR, and 25 (49.0%) and 15 (29.4%) received radiotherapy (median total dose 53.2 Gy) and chemotherapy, respectively. After a median follow-up of 10.0 months, the recurrence and mortality rates were 69.7% (23/33) and 70.8% (34/48), respectively, and the median PFS was 6.0 months. Of the pooled cohort, the actuarial 5-year PFS and OS were 36.3% and 29.2%, respectively, and the estimated median survival time for PFS and OS were 12.8 and 15.2 months, respectively. A multivariate Cox model verified non-GTR (HR 5.537, p < 0.001) and no radiotherapy (HR 3.553, p = 0.008) as independent adverse factors for PFS. The 5-year PFS in patients with or without GTR was 63.8% and 6.3%, respectively, and in patients with or without radiotherapy was 42.7% and 23.1%, respectively. A multivariate model demonstrated non-GTR (HR 9.089, p < 0.001), no radiotherapy (HR 3.126, p = 0.004), and no chemotherapy (HR 3.621, p = 0.004) as independent adverse factors for poor OS. The 5-year OS in patients with GTR, radiotherapy, or chemotherapy was 72.1%, 44.0%, and 58.0%, respectively. In contrast, in patients without GTR, radiotherapy, or chemotherapy, the 5-year OS was 5.8%, 14.3%, and 15.8%, respectively. Overall, in patients receiving GTR plus chemoradiotherapy, the actuarial 5-year PFS and OS were both 87.5%.

CONCLUSIONS

MEPL is a rare neoplastic entity with a poor prognosis. There are no distinguishing radiological features apart from cystic degeneration. Via the pooled analysis, the authors identified independent adjustable factors associated with PFS and OS, from which they advocate for GTR plus chemoradiotherapy with a sufficient dose if tolerable as an optimal treatment to improve outcomes. Future studies with large cohorts will be necessary to verify our findings.