✓ The modulation effects of hexamethylene bisacetamide (HMBA), a differentiation-inducing agent, on growth and differentiation of cells from human malignant glioma cell line SHG-44 were studied. At cytostatic doses (2.5 mM, 5 mM, 7.5 mM, and 10 mM for 15 days), HMBA exerted a marked inhibitory effect on cell proliferation. Exposure to HMBA (5 mM and 10 mM for 12 days) also resulted in an accumulation of cells in G0/G1 phase and a decrease of cells in S phase as analyzed by flow cytometry. The reversible effects of 7.5 mM HMBA and 10 mM HMBA on cell proliferation and 10 mM HMBA on disruption of cell cycle distribution were observed when HMBA was removed from culture media on Day 6 and replaced with HMBA-free media. Colony-forming efficiency (CFE) in soft agar was remarkably decreased by HMBA (2.5 mM, 5 mM, 7.5 mM, and 10 mM for 14 days), and in 7.5 mM HMBA— and 10 mM HMBA—treated cells, the CFEs were reduced to 25% and 12.5%, respectively, of that in untreated cells. Cells treated with HMBA (5 mM and 10 mM for 15 days) remained tumorigenic in athymic nude mice, but the growth rates of the xenografts were much slower than those in the control group. The effects of HMBA on cell proliferation, cell cycle distribution, CFE, and growth of xenografts were dose dependent. A more mature phenotype was confirmed by the morphological changes from spindle shape to large polygonal stellate shape and remarkably elevated expression of glial fibrillary acidic protein in cells exposed to HMBA (5 mM, 10 mM for 15 days). Our results showed that a more differentiated phenotype with marked growth arrest was induced in SHG-44 cells by HMBA.
Xiao-Nan Li, Zi-Wei Du and Qiang Huang
Zachary A. Smith, Zhenzhou Li, Nan-Fu Chen, Dan Raphael and Larry T. Khoo
In this paper, the authors' goal was to demonstrate the clinical and technical nuances of a minimally invasive lateral extracavitary approach (MI-LECA) for thoracic corpectomy and anterior column reconstruction.
A cadaveric feasibility study and the subsequent application of this approach in 3 clinical cases are reported. Six procedures were completed in 3 human cadavers. Minimally invasive, extrapleural thoracic corpectomies were performed with the aid of a 24-mm tubular retraction system, using a posterolateral incision and an oblique approach angle. Fluoroscopy and postprocedural CT scanning, using 3D volumetric averaging software, was used to evaluate the degree of bone removal and decompression. Three clinical cases, including a T-11 burst fracture, a T-7 plasmacytoma, and a T4–5 vertebral body (VB) tuberculosis lesion, were treated using the approach.
At 6 cadaveric levels, the mean circumferential volumetric decompression was 48% ± 16%, and the mean resection of the VB was 72% ± 13%. The mean change in anterior and posterior vertebral height with expansion of the corpectomy cage was 47 and 61 mm, respectively. There were no violations of the pleura or dura. Pedicle screw reliability was 95.8% (23 of 24 screws) with a single lateral breach. All 3 patients in the clinical cohort had excellent clinical outcomes. There was a single pleural tear requiring chest tube drainage. Operative images and a video clip are provided to illustrate the approach.
A minimally invasive lateral extracavitary thoracic corpectomy has the ability to provided excellent spinal cord decompression and VB resection. The procedure can be completed safely and successfully with minimal blood loss and little associated morbidity. This approach has the potential to improve upon established traditional open corridors for posterolateral thoracic corpectomy.
Qian-Nan Wang, Xiang-Yang Bao, Yong Zhang, Qian Zhang, De-Sheng Li and Lian Duan
The objective of this study was to investigate long-term outcomes after encephaloduroarteriosynangiosis (EDAS) for the treatment of hemorrhagic moyamoya disease (MMD) and identify the risk factors for recurrent hemorrhages.
The authors retrospectively reviewed 95 patients with hemorrhagic MMD who were treated with EDAS at 307th Hospital PLA. Clinical features, angiographic findings, and clinical outcomes were investigated. Rebleeding incidences were compared between anterior or posterior hemorrhagic sites. Kaplan-Meier survival analysis and Cox proportional hazards regression models were used to estimate rebleeding risks after EDAS.
The average age at symptom onset was 37.1 years (range 20–54 years) for adult patients. The ratio of female to male patients was 1.16:1. In 61 of 95 hemorrhagic hemispheres (64.2%), the anterior choroidal artery (AChA) or posterior communicating artery (PCoA) was extremely dilated, with extensive branches beyond the choroidal fissure, which only occurred in 28 of 86 nonhemorrhagic hemispheres (32.6%). Fifty-seven incidences were classified as anterior hemorrhages and 38 as posterior. Sixteen of 95 patients (16.8%) suffered cerebral rebleeding after a median follow-up duration of 8.5 years. The annual rebleeding rate was 2.2% per person per year. The incidence rate was higher for the posterior group than for the anterior group, but this difference was not statistically significant (p > 0.05). Cox regression analysis revealed that the age of symptom onset (OR 1.075, 95% CI 1.008–1.147, p = 0.028) was a predictor of rebleeding strokes.
Through long-term follow up, EDAS proved beneficial for patients with hemorrhagic MMD. Dilation of the AChA-PCoA is associated with the initial hemorrhage of MMD, and rebleeding is age-related. Patients with hemorrhagic MMD should undergo follow-up over the course of their lives, even when neurological status is excellent.
Report of two cases
Li Pan, Nan Zhang, Jia Zhong Dai and En Min Wang
✓ The authors report on two patients who underwent radiosurgery for torsion spasm and evaluate the efficiency of gamma knife radiosurgery (GKS) as an alternative treatment.
The first patient was a 33-year-old woman with severe right-sided lower-limb torsion dystonia. The second patient was a 20-year-old man with right-sided upper-limb torsion dystonia. The target was located at the anterior portion of the ventrolateral nucleus. The maximum doses were 150 Gy and 145 Gy, respectively. Double isocenters with a 4-mm collimator were used. Follow up lasted for 18 months and 8 months, respectively. Both patients had excellent clinical improvement 2 to 3 months after GKS, respectively.
The authors believe that GKS may be a safe and efficient treatment for torsion spasm.
Nan Zhang, Li Pan, Jia Zhong Dai, Bin Jiang Wang, En Min Wang and Pei Wu Cai
Object. The purpose of this study was to evaluate the effect on tumor growth and symptom relief in patients with jugular foramen schwannomas after undergoing gamma knife radiosurgery (GKS).
Methods. Between November 1993 and December 2000, 27 patients were treated for jugular foramen schwannomas. The results of GKS in these cases are reviewed. Twelve patients had undergone previous tumor resection and the others underwent GKS as their primary treatment. The mean tumor volume was 13.5 cm3 (range 4.7–35.7 cm3). The mean margin dose was 14.6 Gy (range 9.8–20 Gy). The mean maximum dose was 32.6 Gy (range 25.4–50 Gy). The prescription isodose was 35 to 55%. Twenty-five patients were followed for a mean period of 38.7 months (range 9–90 months). Tumors shrank in 11 patients, remained stable in 13, and enlarged in one patient who underwent a second GKS procedure. Sixteen patients improved and nine remained at their pre-GKS clinical status. No patient developed new cranial nerve deficits after GKS.
Conclusions. The follow-up results indicate that GKS is a safe and effective primary or adjuvant treatment method for the control of jugular foramen schwannomas.
Li Pan, Nan Zhang, En Ming Wang, Bin Jiang Wang, Jia Zhong Dai and Pei Wu Cai
Object. The purpose of this study was to estimate the efficacy of gamma knife radiosurgery (GKS) in controlling tumor growth and endocrinopathy associated with prolactinomas.
Methods. Between 1993 and 1997, 164 of 469 patients with pituitary adenomas treated by GKS harbored prolactinomas. The dose to the tumor margin ranged from 9 to 35 Gy (mean 31.2 Gy), and the visual pathways were exposed to a dose of less than 10 Gy. The mean tumor diameter was 13.4 mm. The mean follow-up time for 128 cases was 33.2 months (range 6–72 months). Tumor control was observed in all but two patients who underwent surgery 18 and 36 months, respectively, after GKS. Clinical cure was achieved in 67 cases.
Clinical improvement was noted with a decrease in the hyperprolactinemia after GKS. Nonetheless, in 31 (29%) of 108 patients who were followed for more than 2 years no improvement in serum prolactin levels was demonstrated, although this could be normalized by bromocriptine administration after treatment. Nine infertile women became pregnant 2 to 13 months after GKS and all gave birth to normal children.
There was no visual deterioration related to GKS. Five women experienced premature menopause. In these patients there was subtotal disappearance of the tumor and an empty sella developed.
Conclusions. Gamma knife radiosurgery as a primary treatment for prolactinomas can be safe and effective both for controlling tumor growth and for normalization of prolactin hypersecretion. A higher margin dose (≥ 30 Gy) seemed to be associated with a better clinical outcome. Gamma knife radiosurgery may make prolactinomas more sensitive to the bromocriptine.
Nan Zhang, Li Pan, Bin Jiang Wang, En Min Wang, Jia Zhong Dai and Pei Wu Cai
Object. The authors analyzed the outcome of 53 patients with cavernous hemangiomas who underwent gamma knife radiosurgery (GKS) and evaluated the benefit of the treatment.
Methods. From 1994 to 1995, 57 patients were treated with GKS for cavernous hemangiomas. The mean margin dose to the lesions was 20.3 Gy (range 14.5–25.2 Gy) and the prescription isodose was 50 to 80%. The mean follow-up period was 4.2 years. Four patients were lost to follow up. In 18 of 28 patients whose chief complaint was seizures, there was a decrease in seizure frequency. Five of 23 patients with hemorrhage suffered rebleeding 4 to 39 months after GKS. Seventeen patients in whom the hemangiomas were located at the frontal or parietal lobe had neurological disability and in five this was severe. Two patients underwent resection of their hemangioma after GKS. Three experienced visual problems. Follow-up imaging demonstrated shrinkage of the lesion in 19 patients.
Conclusions. A higher margin dose (> 16 Gy) may be associated with a reduction in the incidence of rebleeding after GKS. Higher dosage and severe brain edema after GKS may decrease the frequency and intensity of seizures at least temporarily. Gamma knife radiosurgery may play a role in protection against hemorrhage and in reduction of the rate of seizure in selected cases with the appropriate dose.
Nan Zhang, Li Pan, En Min Wang, Jia Zhong Dai, Bin Jiang Wang and Pei Wu Cai
Object. The authors sought to evaluate the effect of gamma knife radiosurgery (GKS) on growth hormone (GH)—producing pituitary adenoma growth and endocrinological response.
Methods. From 1993 to 1997, 79 patients with GH-producing pituitary adenomas were treated with GKS. Seventysix patients had acromegaly. Sixty-eight patients were treated with GKS as the primary procedure. The tumor margin was covered with a 50 to 90% isodose and the margin dose was 18 to 35 Gy (mean 31.3 Gy). The dose to the visual pathways was less than 10 Gy except in one case. Sixty-eight patients (86%) were followed for 6 to 52 months. Growth hormone levels declined with improvement in acromegaly in all cases in the first 6 months after GKS. Normalization of the hormone levels was achieved in 23 (40%) of 58 patients who had been followed for 12 months and in 96% of cases for more than 24 months (43 of 45), or more than 36 months (25 of 26), respectively. With the reduction of GH hormone levels, 12 of 21 patients with hyperglycemia regained a normal blood glucose level (p < 0.001). The tumor shrank in 30 (52%) of 58 patients who had been followed for 12 months (p < 0.01), 39 (87%) of 45 patients for more than 2 years (p = 0.02), and 24 (92%) of 26 patients for more than 36 months. In the remainder of patients tumor growth ceased.
Conclusions. Gamma knife radiosurgery for GH-producing adenomas showed promising results both in hormonal control and tumor shrinkage. A margin dose of more than 30 Gy would seem to be effective in improving the clinical status, reducing high blood glucose levels, and normalizing hypertension.
Yong Zhang, Xiang-Yang Bao, Lian Duan, Wei-Zhong Yang, De-Sheng Li, Zheng-Shan Zhang, Cong Han, Feng Zhao, Qian Zhang and Qian-Nan Wang
The object of this study was to summarize the long-term effect of encephaloduroarteriosynangiosis (EDAS) for the treatment of pediatric moyamoya disease (MMD) and to investigate factors influencing the clinical outcomes of EDAS.
Clinical features, angiographic findings, and clinical outcomes were analyzed among MMD patients younger than 18 years who had been treated with EDAS between 2002 and 2007 at the authors’ institution. The Kaplan-Meier method was used to estimate stroke risk after EDAS. Predictors of neurological outcome were assessed.
One hundred fifteen patients were identified. The mean age at symptom onset was 7.3 ± 4.0 years. The incidence of familial MMD was 11.3%. The female/male ratio was 1:1.16. A total of 232 EDAS procedures were performed, and the incidence of postoperative complications was 3%. Postoperative digital subtraction angiography was performed in 54% of the patients, and about 80% of the hemispheres showed good or excellent results. Neovascularization showed significant correlations with delay time (from symptom onset to first operation), Suzuki stage, and preoperative stroke (all p < 0.05). Clinical follow-up was available in 100 patients with a mean follow-up of 124.4 ± 10.5 months. Ten-year cumulative survival was 96.5% after surgery, and the risk of stroke was 0.33%/person-year. An independent life with no significant disability was reported by 92% of the patients. A good outcome correlated with a low Suzuki stage (p = 0.001). Older children and those without preoperative stroke had better clinical outcomes (p < 0.05).
On the basis of long-term follow-up data, the authors concluded that EDAS is a safe and effective treatment for pediatric MMD, can reduce the risk of subsequent neurological events, and can improve quality of life. The risk of ischemia-related complications was higher in younger patients, and older children showed better outcomes. Compensation was greater with more prominent cerebral ischemia. The long-term clinical outcome largely depended on the presence and extent of preoperative stroke.
Qiao Zuo, Pengfei Yang, Nan Lv, Qinghai Huang, Yu Zhou, Xiaoxi Zhang, Guoli Duan, Yina Wu, Yi Xu, Bo Hong, Rui Zhao, Qiang Li, Yibin Fang, Kaijun Zhao, Dongwei Dai and Jianmin Liu
The authors compared the contemporary perioperative procedure-related complications between coiling with stent placement and coiling without stent placement for acutely ruptured aneurysms treated in a single center after improvement of interventional skills and strategy.
In an institutional review board–approved protocol, 133 patients who underwent coiling with stent placement and 289 patients who underwent coiling without stent placement from January 2012 to December 2014 were consecutively reviewed retrospectively. Baseline characteristics, procedure-related complications and mortality rate, angiographic follow-up results, and clinical outcomes were compared between the two groups. Univariate analysis and logistic regression analysis were performed to determine the association of procedure-related complications of coiling with stent placement with potential risk factors.
The coiling/stent group and coiling/no-stent group were statistically comparable with respect to all baseline characteristics except for aneurysm location (p < 0.001) and parent artery configuration (p = 0.024). The immediate embolization results and clinical outcomes between the two groups showed no significant differences (p = 0.807 and p = 0.611, respectively). The angiographic follow-up results of the coiling in stent group showed a significant higher occlusion rate and lower recurrence rate compared with the coiling/no-stent group (82.5% vs 66.7%, 3.5% vs 14.5%, p = 0.007). Procedure-related intraoperative rupture and thrombosis, postoperative early rebleeding and thrombosis, and external ventricular drainage–related hemorrhagic event occurred in 3.0% (4 of 133), 2.3% (3 of 133), 1.5% (2 of 133), 0.7% (1 of 133), and 0.8% (1 of 133) of the coiling/stent group compared with 1.0% (3 of 289), 1.4% (4 of 289), 1.4% (4 of 289), and 0.7% (2 of 289) of the coiling/no-stent group, respectively (p = 0.288, p = 0.810, p = 1.000, p = 0.315, and p = 1.000, respectively). One patient presented with coil protrusion in the group of coiling without stent. The procedure-related mortality was 1.5% (2 of 133) in the coiling/stent group and 0.7% in the coiling/no-stent group (p = 0.796). Multivariable analysis showed no significant predictors for the total perioperative procedure-related complications, hemorrhagic complications, or ischemic complications.
The perioperative procedure-related complications and mortality rate did not differ significantly between the coiling/stent group and the coiling/no-stent group for patients with acutely ruptured aneurysms. Considering the better angiographic follow-up results, coiling with stent placement might be a feasible, safe, and promising option for treatment in the acute phase of selected wide-necked ruptured intracranial aneurysms.