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Shiwei Wang, Diya Su, Jing Li, Dezhi Li, Hong Wan, Michael Schumacher and Song Liu

OBJECTIVE

In this study, the authors used a surgical model of end-to-side neurorrhaphy between a nerve graft and a donor tibial nerve in adult rats to investigate the optimal conditions for axonal regeneration induced by the donor nerve. They also assessed the importance of a more favorable pathway using a predegenerated nerve graft to attract regenerating axons to regrow into the graft and then directing and improving their growth toward the target in comparison with results obtained with a fresh nerve graft.

METHODS

End-to-side neurorrhaphy was performed between a nerve graft and a donor tibial nerve. The nerve graft was obtained from the left tibial nerve, which was either freshly removed or predegenerated 1 week prior to neurorrhaphy. The donor right tibial nerve was injured by epineurium removal alone, injured by epineurium removal with cross section of 20% or 50% of the total axons at the coaptation site, or left intact. The animals were followed postoperatively for a 6-week period, and outcomes were evaluated by optical microscopy and retrograde labeling to detect the regenerated primary sensory neurons located in the lumbar dorsal root ganglia and spinal motor neurons located in the lumbar spinal ventral horn.

RESULTS

At the end of the follow-up period, no regenerating axons were observed in the nerve grafts when the donor nerve was left intact, and very few axons were detected when the donor nerve was injured by epineurium removal alone. However, numerous regenerating axons appeared in the grafts when the donor nerve was axotomized, and the greatest number was achieved with a 50% cross section axotomized nerve. In the rats with a 50% cross section of the donor nerve, better nerve-like morphology of the grafts was observed, without connective adhesions. When a predegenerated nerve graft was used, more regenerating axons were attracted and elongated with a more regular shape and improved myelination.

CONCLUSIONS

Axonal regrowth into a nerve graft depends on axotomy of the donor nerve after end-to-side neurorrhaphy. More efficient attraction and an improved structure of the regenerating axons were achieved when a predegenerated nerve graft was used. Furthermore, a nerve graft may require a certain number of regenerating axons to maintain a nerve-like morphology.

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Tae-Wan Kim, Hyang-Hwa Ryu, Song-Yuan Li, Chun-Hao Li, Sa-Hoe Lim, Woo-Youl Jang and Shin Jung

OBJECTIVE

In patients with glioblastoma, local invasion of tumor cells causes recurrence and shortens survival. The goal of this study was to determine whether protein disulfide isomerase (PDI) A6 regulates migration and invasion of glioblastoma cells and the associated factors.

METHODS

U87MG cells were treated with either PDIA6 or ADAM17 small interfering RNA (siRNA) fragments or with both types of siRNA fragments, and expression was confirmed by reverse transcription–polymerase chain reaction and Western blot. Migration and invasion were assessed using a wound-healing assay, a Matrigel assay, and an organotypic culture system. After the U87MG cells were treated with siRNAs and epidermal growth factor receptor (EGFR) inhibitors, the expression of matrix metalloproteinase–2 (MMP-2), membrane Type 1-matrix metalloproteinase (MT1-MMP), integrin, phosphorylated focal adhesion kinase (pFAK), and phosphorylated EGFR (pEGFR) was detected by Western blotting and zymography.

RESULTS

U87MG cell migration and invasion increased significantly after inhibition of PDIA6. The MMP-2 activation ratio and ADAM17 activity (as a sheddase of the proligand) increased, and expression of pEGFR, pFAK, integrin α5β3, and MT1-MMP was induced, compared with control levels. Furthermore, heparin-binding epidermal growth factor (EGFR signaling ligand) was highly expressed in PDIA6-knockdown cells. After siPDIA6-transfected U87MG cells were treated with EGFR signaling inhibitors, expression of pFAK, MMP-2, and MT1-MMP decreased and invasion decreased significantly. Simultaneous double-knockdown of PDIA6 and ADAM17 reduced pEGFR and pFAK expression, compared with control levels.

CONCLUSIONS

The authors propose that inhibiting PDIA6 could transduce EGFR signaling by activating and inducing ADAM17 during migration and invasion of U87MG glioblastoma cells. The results of this study suggest that PDIA6 is an important component of EGFR-mediated migration and invasion of U87MG cells. This is the first report of the effects of PDIA6 on migration and invasion in glioblastoma.

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Ganjun Feng, Li Li, Ying Hong, Hao Liu, Yueming Song, Fuxing Pei, Peter X. Ma, Quan Gong and Melanie J. Gupte

Object

The role of oxygen in disc metabolism remains a matter of debate. Whether the effect of hypoxic priming on the nucleus pulposus phenotype can be maintained in vivo is not clear. The goal of the present study was to test the hypothesis that priming in a low oxygen tension in vitro could promote a nucleus pulposus phenotype in vivo.

Methods

Bovine nucleus pulposus cells were seeded in 3D scaffolds and subjected to varying oxygen tensions (2% and 20%) for 3 weeks. The constructs were then implanted subcutaneously for 8 weeks. Changes in the extracellular matrix were evaluated using quantitative real-time reverse transcriptase polymerase chain reaction, glycosaminoglycan (GAG) assay, DNA assay, collagen quantification, and histological and immunohistological analyses.

Results

Hypoxia resulted in greater production of sulfated glycosaminoglycan and higher levels of gene expression for collagen Type II, aggrecan, and SOX-9. Furthermore, after hypoxic priming, the subcutaneously implanted constructs maintained the nucleus pulposus phenotype, which was indicated by a significantly higher amount of glycosaminoglycan and collagen Type II.

Conclusions

Hypoxia enhanced the nucleus pulposus phenotype under experimental conditions both in vitro and in vivo. When used in combination with appropriate scaffold material, nucleus pulposus cells could be regenerated for tissue-engineering applications.

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Liang Xu, Zhonghui Chen, Yong Qiu, Xi Chen, Song Li, Changzhi Du, Qingshuang Zhou and Xu Sun

OBJECTIVE

As scoliosis in arthrogryposis multiplex congenita (AMC) is unusual and the number of cases reviewed in previous studies is also relatively small, no previous study exists that has directly compared the results of spinal deformity correction between AMC and adolescent idiopathic scoliosis (AIS) patients. The aim of this study was to compare the radiographic and clinical outcomes of surgical correction of spinal deformity associated with AMC versus AIS.

METHODS

Twenty-four adolescents with AMC were matched with 48 AIS patients in terms of Cobb angle of main curve, curve pattern, sex, age at surgery, Risser grade, and length of follow-up. Patients in both groups underwent posterior-only spinal correction and fusion procedures. The surgical outcomes and complications were analyzed and compared between the 2 groups.

RESULTS

In comparison to the AIS group, the AMC group had a significantly longer mean operation time (5.6 vs 4.4 hours, p = 0.002), more blood loss (1620 ± 250 ml vs 840 ± 260 ml, p < 0.001), and more fusion levels (14.1 ± 2.3 levels vs 12.4 ± 2.5 levels, p = 0.007) as well as a lower correction rate (44.3% ± 11.1% vs 70.8% ± 12.4%, p < 0.001) and a higher rate of loss of correction (5.0% ± 3.1% vs 2.1% ± 1.9%, p < 0.001). Nine patients in the AMC group had preoperative pelvic obliquity, which was corrected from a mean of 14.2° ± 8.4° to a mean of 4.3° ± 3.2° (p < 0.001) after the surgery. The thoracic lordosis and sagittal vertical axis were significantly improved in the AMC group. Notably, however, the AMC group was found to have higher rates of screw malpositioning (15.9% vs 9.5%, p = 0.002) and complications (8/24 [33.3%] vs 4/48 [8.3%], p = 0.016) as compared to the AIS group.

CONCLUSIONS

Correction of AMC-associated scoliosis tends to require a longer operating time and involve more fusion levels but results in less correction, more blood loss, and more complications, in comparison with AIS. In addition, more attention should be paid to pelvic obliquity and sagittal hyperlordosis in AMC patients.

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Zhonghui Chen, Song Li, Yong Qiu, Zezhang Zhu, Xi Chen, Liang Xu and Xu Sun

OBJECTIVE

Although the vertical expandable prosthetic titanium rib (VEPTR) and growing rod instrumentation (GRI) encourage spinal growth via regular lengthening, they can create different results because of their different fixation patterns and mechanisms in correcting scoliosis. Previous studies have focused comparisons on coronal plane deformity with minimal attention to the sagittal profile. In this retrospective study, the authors aimed to compare the evolution of the sagittal spinal profile in early-onset scoliosis (EOS) treated with VEPTR versus GRI.

METHODS

The data for 11 patients with VEPTR and 22 with GRI were reviewed. All patients had more than 2 years’ follow-up with more than 2 lengthening procedures. Radiographic measurements were performed before and after the index surgery and at the latest follow-up. The complications in both groups were recorded.

RESULTS

Patients in both groups had similar diagnoses, age at the index surgery, and number of lengthening procedures. The changes in the major coronal Cobb angle and T1–S1 spinal height were not significantly different between the 2 groups. Compared with the GRI group, the VEPTR group had less correction in thoracic kyphosis (23% ± 12% vs 44% ± 16%, p < 0.001) after the index surgery and experienced a greater correction loss in thoracic kyphosis (46% ± 18% vs 11% ± 8%, p < 0.001) at the latest follow-up. Although the increase in the proximal junctional angle was not significantly different (VEPTR: 7° ± 4° vs GRI: 8° ± 5°, p = 0.569), the incidence of proximal junctional kyphosis was relatively lower in the VEPTR group (VEPTR: 18.2% vs GRI: 22.7%). No significant changes in the spinopelvic parameters were observed, while the sagittal vertical axis showed a tendency toward a neutral position in both groups. The overall complication rate was higher in the VEPTR group than in the GRI group (72.7% vs 54.5%).

CONCLUSIONS

The VEPTR had coronal correction and spinal growth results similar to those with GRI. In the sagittal plane, however, the VEPTR was not comparable to the GRI in controlling thoracic kyphosis. Thus, for hyperkyphotic EOS patients, GRI is recommended over VEPTR.

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Feng Zhou, Zixiao Yang, Wei Zhu, Liang Chen, Jianping Song, Kai Quan, Sichen Li, Peiliang Li, Zhiguang Pan, Peixi Liu and Ying Mao

OBJECTIVE

Epidermoid cysts of the cavernous sinus (CS) are rare, and no large case series of these lesions has been reported. In this study, the authors retrospectively reviewed the outcomes of the surgical management of CS epidermoid cysts undertaken at their center and performed a review of any such cysts reported in the literature over the past 40 years.

METHODS

Clinical data were obtained on 31 patients with CS epidermoid cysts that had been surgically treated at the authors’ hospital between 2001 and 2016. The patients’ medical records, imaging data, and follow-up outcomes were retrospectively analyzed. The related literature from the past 40 years (18 articles, 20 patients) was also evaluated.

RESULTS

The most common chief complaints were facial numbness or hypesthesia (64.5%), absent corneal reflex (45.2%), and abducens or oculomotor nerve deficit (35.5%). On MRI, 51.6% of the epidermoid cysts showed low T1 signals and equal or high T2 signals. In the other lesions, the radiological findings varied considerably given differences in the composition of the cysts. Surgery was performed via the extradural approach (58.1%), intradural approach (32.3%), or a combined approach (9.7%). After the operation, symptoms remained similar or improved in 90.3% of patients and new oculomotor paralysis developed after the operation in 9.7% of patients. Seven patients (22.6%) developed meningitis postoperatively (5 aseptic and 2 septic), and all of them recovered. All patients achieved good recovery before discharge (Karnofsky Performance Status score ≥ 70). Over an average follow-up of 4.6 ± 3.0 years in 25 patients (80.6%), no recurrence or reoperation occurred, regardless of whether total or subtotal resection of the capsule had been achieved.

CONCLUSIONS

Both the extradural and intradural approaches can enable satisfactory lesion resection. A favorable prognosis and symptomatic improvement can be expected after both total and subtotal capsule resections. Total capsule resection is encouraged to minimize the possibility of recurrence provided that the resection can be safely performed.

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Shiwei Wang, Diya Su, Jing Li, Dezhi Li, Hong Wan, Michael Schumacher and Song Liu

OBJECTIVE

In this study, the authors used a surgical model of end-to-side neurorrhaphy between a nerve graft and a donor tibial nerve in adult rats to investigate the optimal conditions for axonal regeneration induced by the donor nerve. They also assessed the importance of a more favorable pathway using a predegenerated nerve graft to attract regenerating axons to regrow into the graft and then directing and improving their growth toward the target in comparison with results obtained with a fresh nerve graft.

METHODS

End-to-side neurorrhaphy was performed between a nerve graft and a donor tibial nerve. The nerve graft was obtained from the left tibial nerve, which was either freshly removed or predegenerated 1 week prior to neurorrhaphy. The donor right tibial nerve was injured by epineurium removal alone, injured by epineurium removal with cross section of 20% or 50% of the total axons at the coaptation site, or left intact. The animals were followed postoperatively for a 6-week period, and outcomes were evaluated by optical microscopy and retrograde labeling to detect the regenerated primary sensory neurons located in the lumbar dorsal root ganglia and spinal motor neurons located in the lumbar spinal ventral horn.

RESULTS

At the end of the follow-up period, no regenerating axons were observed in the nerve grafts when the donor nerve was left intact, and very few axons were detected when the donor nerve was injured by epineurium removal alone. However, numerous regenerating axons appeared in the grafts when the donor nerve was axotomized, and the greatest number was achieved with a 50% cross section axotomized nerve. In the rats with a 50% cross section of the donor nerve, better nerve-like morphology of the grafts was observed, without connective adhesions. When a predegenerated nerve graft was used, more regenerating axons were attracted and elongated with a more regular shape and improved myelination.

CONCLUSIONS

Axonal regrowth into a nerve graft depends on axotomy of the donor nerve after end-to-side neurorrhaphy. More efficient attraction and an improved structure of the regenerating axons were achieved when a predegenerated nerve graft was used. Furthermore, a nerve graft may require a certain number of regenerating axons to maintain a nerve-like morphology.

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Song-Bai Gui, Sheng-Yuan Yu, Lei Cao, Ji-wei Bai, Xin-Sheng Wang, Chu-Zhong Li and Ya-Zhuo Zhang

OBJECTIVE

At present, endoscopic treatment is advised as the first procedure in cases of suprasellar arachnoid cysts (SSCs) with hydrocephalus. However, the appropriate therapy for SSCs without hydrocephalus has not been fully determined yet because such cases are very rare and because it is usually difficult to perform the neuroendoscopic procedure in patients without ventriculomegaly given difficulties with ventricular cannulation and the narrow foramen of Monro. The purpose of this study was to find out the value of navigation-guided neuroendoscopic ventriculocystocisternostomy (VCC) for SSCs without lateral ventriculomegaly.

METHODS

Five consecutive patients with SSC without hydrocephalus were surgically treated using endoscopic fenestration (VCC) guided by navigation between March 2014 and November 2015. The surgical technique, success rate, and patient outcomes were assessed and compared with those from hydrocephalic patients managed in a similar fashion.

RESULTS

The small ventricles were successfully cannulated using navigational tracking, and the VCC was accomplished in all patients. There were no operative complications related to the endoscopic procedure. In all patients the SSC decreased in size and symptoms improved postoperatively (mean follow-up 10.4 months).

CONCLUSIONS

Endoscopic VCC can be performed as an effective, safe, and simple treatment option by using intraoperative image-based neuronavigation in SSC patients without hydrocephalus. The image-guided neuroendoscopic procedure improved the accuracy of the endoscopic approach and minimized brain trauma. The absence of hydrocephalus in patients with SSC may not be a contraindication to endoscopic treatment.

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Liang Xu, Yong Qiu, Zhonghui Chen, Benlong Shi, Xi Chen, Song Li, Changzhi Du, Zezhang Zhu and Xu Sun

OBJECTIVE

This study aimed to evaluate the correction results of traditional dual growing rods (DGRs) on axial rotation using CT scans and to further explore the relationships between axial and torso deformities in patients with early-onset scoliosis (EOS).

METHODS

Patients with EOS who were treated with traditional DGRs between January 2006 and December 2014 were retrospectively reviewed. Plain radiographs were used to assess the degree of coronal and sagittal deformity. The apical vertebral rotation (AVR) and rib hump (RH) were measured on CT scans at the apical vertebra. Pearson or Spearman rank correlation analyses were used to analyze the associations between spinal and torso deformities.

RESULTS

A total of 27 patients (10 boys and 17 girls, average age 6.5 ± 1.7 years) were enrolled in this study. The average number of lengthenings per patient was 5.0 ± 1.9, with a mean follow-up duration of 52.9 ± 18.2 months. The apical vertebral translation, apical vertebral body–rib ratio (AVB-R), AVR, and RH parameters were significantly decreased after the initial surgery (p < 0.05) but showed notable progression at the latest follow-up evaluation (p < 0.05). The preoperative AVR and its correction after index surgery were significantly correlated with the preoperative values as well as with the corrections of the major Cobb angle, AVB-R, and RH. During the follow-up period, significant correlations were found between the deterioration of AVR and the AVB-R and also between the deterioration of AVR and the RH from the initial surgery to the latest follow-up.

CONCLUSIONS

Significant AVR correction can be achieved by DGR techniques after the initial surgery. However, this technique weakly prevents the deterioration of AVR during the follow-up period.

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Dong Liu, Yanhe Li, Yipei Zhang, Zhiyuan Zhang, Guoxiang Song and Desheng Xu

OBJECTIVE

This article is a preliminary evaluation of the efficacy of volume-staged Gamma Knife radiosurgery (GKRS) in the treatment of patients with orbital venous malformations (OVMs).

METHODS

Twenty patients with moderate to large OVMs were treated with volume-staged GKRS between March 2005 and October 2015. The series included 8 male and 12 female patients with an average age of 22.5 years (range 9–45 years). The diagnoses were confirmed intraoperatively and at pathological examination in 14 cases and presumed in accordance with clinical and imaging findings in 6 cases. The median OVM volume was 12.2 cm3 (range 7.1–34.6 cm3). The median interval between stages was 10 months (range 6–12 months). The tumor margin dose for each stage ranged from 11.0 to 13.5 Gy. The median duration of follow-up was 45.5 months (range 18–98 months).

RESULTS

Periodically scheduled MRI studies demonstrated evidence of a significant reduction of the original OVM volume in all cases. Visual acuity (VA) was preserved in 18 cases (90%). Five patients (25%) experienced vision improvement of varying degrees, and 13 (65%) experienced long-term preservation of VA at their pre-GKRS level. Deterioration in VA was observed in only 2 cases (10%). MRI demonstrated OVM regression after treatment in all cases, and all patients were found to have reduction of exophthalmos after volume-staged GKRS. Follow-up MRI revealed recurrence in only 1 case (5%). Three patients (15%) developed transient conjunctival edema.

CONCLUSIONS

This retrospective investigation indicates that volume-staged GKRS provides an effective management option in selected patients with OVMs, providing excellent visual outcomes. The study adds substantial support for volume-staged GKRS as a major treatment for OVMs.