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Jianwen Dong, Limin Rong, Feng Feng, Bin Liu, Yichun Xu, Qiyou Wang, Ruiqiang Chen and Peigen Xie

Object

Treatment of patients with single-segment degenerative lumbar instability using unilateral pedicle screw fixation can achieve stability and fusion rates similar to those of bilateral pedicle screw fixation. The aim of this study was to analyze the clinical outcome of using unilateral pedicle screw fixation through a tubular retractor via the Wiltse approach to treat single-segment degenerative lumbar instability.

Methods

Thirty-nine consecutive patients with single-segment, low-grade, degenerative lumbar instability were randomly assigned to treatment with either unilateral (n = 20) or bilateral (n = 19) pedicle screw fixation. In the unilateral group, patients underwent unilateral posterior lumbar interbody fusion (PLIF) and ipsilateral pedicle screw fixation through a tubular retractor via the Wiltse approach. In the bilateral group, patients underwent modified bilateral PLIF with bilateral pedicle screw fixation via the posterior midline approach. During follow-up, patients were evaluated using a visual analog scale (VAS), the Japanese Orthopaedic Association (JOA) score, and the Oswestry Disability Index.

Results

The unilateral group had a shorter operative duration (p < 0.05) and less blood loss (p < 0.001). All patients completed more than 2 years of follow-up (mean 36 months). In general, the time trends in improvement on the VAS and JOA differed slightly between the groups through 2 years, but no significant difference in back pain VAS score or leg pain VAS score was found between these 2 groups at the 2-year follow-up. Complete bone fusion was shown on CT in all patients at the 2-year follow-up.

Conclusions

Unilateral pedicle screw fixation through a tubular retractor via the Wiltse approach appears to be as safe and effective as bilateral pedicle screw fixation for the treatment of single-segment degenerative lumbar instability.

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Qiang Jia, Yanhe Li, Desheng Xu, Zhenjiang Li, Zhiyuan Zhang, Yipei Zhang, Dong Liu, Xiaomin Liu, Peiyu Pu and Chunsheng Kang

Object

The authors sought to evaluate modification of the radiation response of C6 glioma cells in vitro and in vivo by inhibiting the expression of Ku70. To do so they investigated the effect of gene transfer involving a recombinant replication-defective adenovirus containing Ku70 short hairpin RNA (Ad-Ku70shRNA) combined with Gamma Knife treatment (GKT).

Methods

First, Ad-Ku70shRNA was transfected into C6 glioma cells and the expression of Ku70 was measured using Western blot analysis. In vitro, phenotypical changes in C6 cells, including proliferation, cell cycle modification, invasion ability, and apoptosis were evaluated using the MTT (3′(4,5-dimethylthiazol-2-yl)2,5-diphenyltetrazolium bromide) assay, Western blot analysis, and cell flow cytometry. In vivo, parental C6 cells transfected with Ad-Ku70shRNA were implanted stereotactically into the right caudate nucleus in Sprague-Dawley rats. After GKS, apoptosis was analyzed using the TUNEL (terminal deoxynucleotidyl transferase–mediated deoxyuridine triphosphate nick-end labeling) method. The inhibitory effects on growth and invasion that were induced by expression of proliferating cell nuclear antigen and matrix metalloproteinase–9 were determined using immunohistochemical analyses.

Results

The expression of Ku70 was clearly inhibited in C6 cells after transfection with Ad-Ku70shRNA. In vitro following transfection, the C6 cells showed improved responses to GKT, including suppression of proliferation and invasion as well as an increased apoptosis index. In vivo following transfection of Ad-Ku70shRNA, the therapeutic efficacy of GKT in rats with C6 gliomas was greatly enhanced and survival times in these animals were prolonged.

Conclusions

Our data support the potential for downregulation of Ku70 expression in enhancing the radiosensitivity of gliomas. The findings of our study indicate that targeted gene therapy–mediated inactivation of Ku70 may represent a promising strategy in improving the radioresponsiveness of gliomas to GKT.

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Qian Zhang, Yaping Liu, Dong Zhang, Rong Wang, Yan Zhang, Shuo Wang, Lanbing Yu, Chaoxia Lu, Fang Liu, Jian Zhou, Xue Zhang and Jizong Zhao

OBJECTIVE

Moyamoya disease (MMD) is a rare, genetically heterogeneous cerebrovascular disease. The authors conducted a genetic study of really interesting new gene (RING) finger protein 213 (RNF213); actin alpha 2 (ACTA2); BRCA1/BRCA2-containing complex subunit 3 (BRCC3); and guanylate cyclase 1, soluble, alpha 3 (GUCY1A3) as well as a clinical phenotype analysis in Chinese MMD patients to determine whether genetic differences are responsible for the different clinical features that appear in MMD in different ethnicities.

METHODS

A panel was designed to identify disease-causing mutations in MMD genes and those involved in related disorders (RNF213, ACTA2, BRCC3, and GUCY1A3). The panel was used to detect disease-causing mutations in 255 Chinese MMD patients. Genotype and allele frequencies were compared between patients and 300 controls. A mutation segregation analysis was performed in 34 families, and genotype-phenotype correlations were made.

RESULTS

Twenty-seven rare missense variants of RNF213 were identified and were not found in controls. Among them, p.R4810K was identified in 31.4% of patients (80 of 255) with MMD. Significantly higher frequencies of the A allele and G/A genotype of p.R4810K were observed in MMD patients compared with controls (χ2 = 104.166, p < 0.000). Twenty-five rare variants were identified in 10.6% of patients (27 of 255) without p.R4810K variants. Segregation analysis supported an association between MMD and 3 variants. No possible disease-causing mutations were identified in ACTA2, BRCC3, or GUCY1A3. Compared with patients without the rare variants in RNF213, the p.R4810K heterozygous patients were younger at diagnosis (25 vs 29 years old, p = 0.049) and had more familial cases (24% vs 4.4%, p = 0.000), ischemic cases (81.3% vs 67.5%, p = 0.037), and involvement of the posterior cerebral artery (52% vs 32.5%, p = 0.007).

CONCLUSIONS

RNF213 is the major susceptibility gene in Chinese MMD patients. The spectrum of rare variants identified in Chinese MMD patients was diverse. Compared to patients without the rare variants in RNF213, the p.R4810K heterozygous patients exhibited different clinical features.

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Guo-chen Sun, Xiao-lei Chen, Yuan-zheng Hou, Xin-guang Yu, Xiao-dong Ma, Gang Liu, Lei Liu, Jia-shu Zhang, Hao Tang, Ru-Yuan Zhu, Ding-Biao Zhou and Bai-nan Xu

OBJECTIVE

Endoscopic removal of intracerebral hematomas is becoming increasingly common, but there is no standard technique. The authors explored the use of a simple image-guided endoscopic method for removal of spontaneous supratentorial hematomas.

METHODS

Virtual reality technology based on a hospital picture archiving and communications systems (PACS) was used in 3D hematoma visualization and surgical planning. Augmented reality based on an Android smartphone app, Sina neurosurgical assist, allowed a projection of the hematoma to be seen on the patient's scalp to facilitate selection of the best trajectory to the center of the hematoma. A obturator and transparent sheath were used to establish a working channel, and an endoscope and a metal suction apparatus were used to remove the hematoma.

RESULTS

A total of 25 patients were included in the study, including 18 with putamen hemorrhages and 7 with lobar cerebral hemorrhages. Virtual reality combined with augmented reality helped in achieving the desired position with the obturator and sheath. The median time from the initial surgical incision to completion of closure was 50 minutes (range 40–70 minutes). The actual endoscopic operating time was 30 (range 15–50) minutes. The median blood loss was 80 (range 40–150) ml. No patient experienced postoperative rebleeding. The average hematoma evacuation rate was 97%. The mean (± SD) preoperative Glasgow Coma Scale (GCS) score was 6.7 ± 3.2; 1 week after hematoma evacuation the mean GCS score had improved to 11.9 ± 3.1 (p < 0.01).

CONCLUSIONS

Virtual reality using hospital PACS and augmented reality with a smartphone app helped precisely localize hematomas and plan the appropriate endoscopic approach. A transparent sheath helped establish a surgical channel, and an endoscope enabled observation of the hematoma's location to achieve satisfactory hematoma removal.

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Dong Liu, Desheng Xu, Zhiyuan Zhang, Yipei Zhang, Yanhe Li, Xiaomin Liu, Qiang Jia, Ligao Zheng and Guoxiang Song

Object

The goal of this study was to assess the long-term results of Gamma Knife surgery (GKS) in patients harboring an optic nerve sheath meningioma (ONSM).

Methods

Thirty patients harboring an ONSM were treated with GKS between 1998 and 2003. Gamma Knife surgery was performed as the sole treatment option in 21 of these patients and resection had been performed previously in 9 patients. The mean volume of the tumor at the time of GKS was 3.6 cm3 (range 1.4–9.7 cm3), and the mean prescription peripheral dose was 13.3 Gy (range 10–17 Gy). The mean number of isocenters used to treat these lesions was 8 (range 5–14 isocenters).

Results

At a median follow-up of 56 months, visual acuity improved in 11 patients, remained stable in 13 patients (including 4 patients who were completely blind before GKS), and deteriorated in 6 patients. Follow-up images were available in all patients and showed tumor regression in 20 patients and stable tumor in 8 patients. Persistent imaging evidence of progression was only present in 2 patients. With the exception of reversible conjunctival edema in 4 cases, no other serious acute side effect was observed.

Conclusions

Gamma Knife surgery provides long-term tumor control for ONSM. The results of this study add substantial evidence that GKS may definitely become a standard treatment approach in selected cases of ONSM.

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Desheng Xu, Dong Liu, Zhiyuan Zhang, Yipei Zhang, Yanhe Li, Xiaomin Liu, Qiang Jia, Ligao Zheng and Guoxiang Song

Object

The authors evaluated the results they obtained using Gamma Knife surgery (GKS) in patients with orbital tumors.

Methods

This is a retrospective clinical evaluation of 202 patients with orbital tumors who were treated with GKS between September 1995 and October 2008. The series included 84 men and 118 women with a mean age of 39.5 ± 14.6 years (range 5–85 years). The diagnoses were determined based on pathological analyses in 113 patients and presumed based on characteristic clinical and imaging findings in 89 patients. There were 84 meningiomas, 38 epithelial tumors of the lacrimal gland, 23 schwannomas, 18 malignant choroidal melanomas, 12 optic nerve gliomas, 11 orbital metastases, 10 pseudotumors of the orbit, 3 retinoblastomas, and 3 cases of fibromatosis. The median target volume was 5.4 cm3 (range 0.04–35.6 cm3). The tumor margin dose ranged from 10 to 40 Gy.

Results

At a median follow-up period of 34.5 ± 14.7 months (range 12–114 months), tumor shrinkage was observed in 118 patients (58.4%) and stable tumor size in 71 patients (35.1%). Regularly scheduled neuroimaging studies demonstrated evidence of tumor progression in only 13 patients (6.4%): 9 of these patients underwent repeated GKS and 4 received surgical treatment. Visual acuity was preserved in 129 patients. Seventy-two patients experienced some degree of improvement in vision. Severe deterioration of visual acuity was found in 18 of 147 patients who had useful vision before treatment. Nineteen patients (9.4%) experienced transient conjunctival edema; no other serious acute side effect was observed.

Conclusions

Gamma Knife surgery provides an effective management strategy in patients with orbital tumors; it achieves excellent preservation of neurological function and is associated with few treatment-related complications.

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Xing-ju Liu, Dong Zhang, Shuo Wang, Yuan-li Zhao, Mario Teo, Rong Wang, Yong Cao, Xun Ye, Shuai Kang and Ji-Zong Zhao

OBJECT

The aim of this study was to describe the baseline clinical features and long-term outcomes of patients with moyamoya disease (MMD) based on a 25-year period at a single center in China.

METHODS

 Data obtained in 528 consecutive patients with MMD treated at the authors' hospital from 1984 to 2010 were reviewed retrospectively. Events of transient ischemic attack, new infarction, and hemorrhage were included. The Kaplan-Meier risk of stroke was calculated.

RESULTS

 The mean (± SD) patient age was 26 ± 13 years (range 2–67 years), and the female/male ratio was 0.9:1. There were 332 cases of ischemia and 196 hemorrhages. Adults had a higher rate of bleeding than children (50.7% vs 14.0%, respectively; p < 0.001). One hundred twenty-two patients were treated conservatively, and 406 patients underwent revascularization procedures. Of 528 patients, 331 (62.7%) had at least 1 year of follow-up (median 39.5 months) and data from these patients were analyzed. Rebleeding and mortality rates in patients with hemorrhagic MMD (n = 104) were higher than in those with ischemic MMD (n = 227) (26.9% vs 2.2% [p < 0.001] and 4.8% vs 0.4% [p < 0.05], respectively). Twenty-five of 60 (41.7%) conservatively treated patients and 8 of 271 (2.9%) surgically treated patients experienced rebleeding events, a difference that was significant in the Kaplan-Meier curve of rebleeding (p < 0.01). An improvement in perfusion was found in 164 of 224 (73.2%) surgically treated patients 1 month after discharge. However, there was no significant difference in the rate of ischemic events in the surgical and conservative groups (18.8% and 28.3%, respectively; p = 0.09). Among the 104 hemorrhagic cases, rebleeding attacks were observed in 25 patients in the nonsurgical group (n = 60) and 3 patients in the surgical group (n = 44) (41.7% and 6.8%, respectively; OR 9.7 [95% CI 2.7–35.0]; p < 0.01).

CONCLUSIONS

 There was no difference in the sex distribution of Chinese patients with MMD. Patients with hemorrhagic MMD had a much higher rate of rebleeding and poorer prognosis than those with the ischemic type. Surgical revascularization procedures can improve cerebral perfusion and have a positive impact in preventing rebleeding in patients with hemorrhagic MMD.

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Xiaofeng Deng, Faliang Gao, Dong Zhang, Yan Zhang, Rong Wang, Shuo Wang, Yong Cao, Yuanli Zhao, Yuesong Pan, Xingju Liu, Qian Zhang and Jizong Zhao

OBJECTIVE

The optimal surgical modality for moyamoya disease (MMD) remains unclear. The aim of this study was to compare the surgical effects of direct bypass (DB) and indirect bypass (IB) in the treatment of adult ischemic-type MMD.

METHODS

Adult patients with ischemic-type MMD who underwent either DB or IB from 2009 to 2015 were identified retrospectively from a prospective database. Patients lost to follow-up or with a follow-up period less than 12 months were excluded. Recurrent stroke events and modified Rankin Scale (mRS) scores at the last follow-up were compared between the 2 surgical groups after 1:1 propensity score matching.

RESULTS

A total of 220 patients were considered, including 143 patients who underwent DB and 77 patients who underwent IB. After propensity score matching, 70 pairs were obtained. The median follow-up period was 40.5 months (range 14–75 months) in the DB group and 31.5 months (range 14–71 months) in the IB group (p = 0.004). Kaplan-Meier analysis showed that patients who received DB had a longer stroke-free time (mean 72.1 months) compared with patients who received IB (mean 61.0 months) (p = 0.045). Good neurological status (mRS score ≤ 2) was achieved in 64 patients in the DB group (91.4%) and 66 patients in the IB group (94.3%), but there was no significant difference (p = 0.512).

CONCLUSIONS

Although neurological function outcome was not determined by the surgical modality, DB is more effective in preventing recurrent ischemic strokes than IB for adult ischemic-type MMD.

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Xing Wu, Jin Hu, Liangfu Zhou, Ying Mao, Bojie Yang, Liang Gao, Rong Xie, Feng Xu, Dong Zhang, Jun Liu and Jianhong Zhu

Object

Mesenchymal stem cells (MSCs) have been shown to migrate toward tumors, but their distribution pattern in gliomas has not been completely portrayed. The primary purpose of the study was to assay the tropism capacity of MSCs to gliomas, to delineate the pattern of MSC distribution in gliomas after systemic injection, and to track the migration and incorporation of magnetically labeled MSCs using 1.5-T magnetic resonance (MR) imaging.

Methods

The MSCs from Fischer 344 rats were colabeled with superparamagnetic iron oxide nanoparticles (SPIO) and enhanced green fluorescent protein (EGFP). The tropism capacity of MSCs was quantitatively assayed in vitro using the Transwell system. To track the migration of MSCs in vivo, MR imaging was performed both 7 and 14 days after systemic administration of labeled MSCs. After MR imaging, the distribution patterns of MSCs in rats with gliomas were examined using Prussian blue and fluorescence staining.

Results

The in vitro study showed that MSCs possessed significantly greater migratory capacity than fibroblast cells (p < 0.001) and that lysis of F98 glioma cells and cultured F98 cells showed a greater capacity to induce migration of cells than other stimuli (p < 0.05). Seven days after MSC transplantation, the SPIO–EGFP colabeled cells were distributed throughout the tumor, where a well-defined dark hypointense region was represented on gradient echo sequences. After 14 days, most of the colabeled MSCs were found at the border between the tumor and normal parenchyma, which was represented on gradient echo sequences as diluted amorphous dark areas at the edge of the tumors.

Conclusions

This study demonstrated that systemically transplanted MSCs migrate toward gliomas with high specificity in a temporal–spatial pattern, which can be tracked using MR imaging.

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Zihao Chen, Liangming Zhang, Jianwen Dong, Peigen Xie, Bin Liu, Qiyou Wang, Ruiqiang Chen, Feng Feng, Bu Yang, Tao Shu, Shangfu Li, Yang Yang, Lei He, Mao Pang and Limin Rong

OBJECTIVE

A prospective randomized controlled study was conducted to clarify whether percutaneous transforaminal endoscopic discectomy (PTED) results in better clinical outcomes and less surgical trauma than microendoscopic discectomy (MED).

METHODS

In this single-center, open-label, randomized controlled trial, patients were included if they had persistent signs and symptoms of radiculopathy with corresponding imaging-confirmed lumbar disc herniation. Patients were randomly allocated to the PTED or the MED group by computer-generated randomization codes. The primary outcome was the Oswestry Disability Index (ODI) score 1 year after surgery. Secondary outcomes included scores of the Medical Outcomes Study 36-Item Short-Form Health Survey bodily pain and physical function scales, EuroQol Group’s EQ-5D , and the visual analog scales for back pain and leg pain. Data including duration of operation, in-bed time, length of hospital stay, surgical cost and total hospital cost, complications, and reoperations were recorded.

RESULTS

A total of 153 participants were randomly assigned to 2 treatment groups (PTED vs MED), and 89.5% (137 patients) completed 1 year of follow-up. Primary and secondary outcomes did not differ significantly between the treatment groups at each prespecified follow-up point (p > 0.05). For PTED, there was less postoperative improvement in ODI score in the median herniation subgroup at 1 week (p = 0.027), 3 months (p = 0.013), 6 months (p = 0.027), and 1 year (p = 0.028) compared with the paramedian subgroup. For MED, there was significantly less improvement in ODI score at 3 months (p = 0.008), 6 months (p = 0.028), and 1 year (p = 0.028) in the far-lateral herniation subgroup compared with the paramedian subgroup. The total complication rate over the course of 1 year was 13.75% in the PTED group and 16.44% in the MED group (p = 0.642). Five patients (6.25%) in the PTED group and 3 patients (4.11%) in the MED group suffered from residue/recurrence of herniation, for which reoperation was required.

CONCLUSIONS

Over the 1-year follow-up period, PTED did not show superior clinical outcomes and did not seem to be a safer procedure for patients with lumbar disc herniation compared with MED. PTED had inferior results for median disc herniation, whereas MED did not seem to be the best treatment option for far-lateral disc herniation.

Clinical trial registration no.: NCT01997086 (clinicaltrials.gov).