Zhongjun Liu

Reconstruction of the Upper Cervical Spine Using a Personalized 3D-Printed Vertebral Body in an Adolescent With Ewing Sarcoma.

Study Design. Case report. Objective: To describe a three-dimensional (3D) printed axial vertebral body used in upper cervical spine reconstruction after a C2 Ewing sarcoma resection in an adolescent boy. Summary of Background Data. Ewing sarcoma is a malignant musculoskeletal neoplasm with a peak incidence in adolescents. Cervical spine as the primary site of the tumor has been related to a worse prognosis. Tumor resection is particularly challenging in the atlantoaxial region due to complexity of the anatomy, necessity for extensive resection according to oncological principles, and a lack of specialized implants for reconstruction. 3D printing refers to a process where 3D objects are created through successive layering of material under computer control. Although this technology potentially enables accurate fabrication of patient-specific orthopedic implants, literature on its utilization in this regard is rare. Methods. A 12-year-old boy with a C2 Ewing sarcoma underwent a staged spondylectomy. Wide resection of the posterior elements was first performed. Two weeks later, a high anterior retropharyngeal approach was taken to remove the remains of the C2 vertebra. A customized artificial vertebral body fabricated according to a computer model using titanium alloy powder was inserted to replace the defect between C1 and C3. The microstructure of the implant was optimized for better biomechanical stability and enhanced bone healing. Results. Patient had an uneventful recovery and began to ambulate on postoperative day 7. Adjuvant treatment commenced 3 weeks after the surgery. He was tumor-free at the 1-year follow-up. Computed tomography studies revealed evidence of implant osseointegration and no subsidence or displacement of the construct. Conclusion. This is a case example on the concept of personalized precision medicine in a surgical setting and demonstrates how 3D-printed, patient-specific implants may bring individualized solutions to rare problems wherein restoration of the specific anatomy of each patient is a key prognostic factor. Level of Evidence: 5

Integrated miRNA-mRNA Analysis Revealing the Potential Roles of miRNAs in Chordomas

Introduction Emerging evidence suggests that microRNAs (miRNAs) are crucially involved in tumorigenesis and that paired expression profiles of miRNAs and mRNAs can be used to identify functional miRNA-target relationships with high precision. However, no studies have applied integrated analysis to miRNA and mRNA profiles in chordomas. The purpose of this study was to provide insights into the pathogenesis of chordomas by using this integrated analysis method. Methods Differentially expressed miRNAs and mRNAs of chordomas (n = 3) and notochord tissues (n = 3) were analyzed by using microarrays with hierarchical clustering analysis. Subsequently, the target genes of the differentially expressed miRNAs were predicted and overlapped with the differentially expressed mRNAs. Then, GO and pathway analyses were performed for the intersecting genes. Results The microarray analysis indicated that 33 miRNAs and 2,791 mRNAs were significantly dysregulated between the two groups. Among the 2,791 mRNAs, 911 overlapped with putative miRNA target genes. A pathway analysis showed that the MAPK pathway was consistently enriched in the chordoma tissue and that miR-149-3p, miR-663a, miR-1908, miR-2861 and miR-3185 likely play important roles in the regulation of MAPK pathways. Furthermore, the Notch signaling pathway and the loss of the calcification or ossification capacity of the notochord may also be involved in chordoma pathogenesis. Conclusion This study provides an integrated dataset of the miRNA and mRNA profiles in chordomas, and the results demonstrate that not only the MAPK pathway and its related miRNAs but also the Notch pathway may be involved in chordoma development. The occurrence of chordoma may be associated with dysfunctional calcification or ossification of the notochord.

Interferon alfa-2b for recurrent and metastatic giant cell tumor of the spine: report of two cases.

Study Design. Case report. Objective. To demonstrate that interferon alfa-2b is a therapeutic option for obtaining long-term control of recurrent and metastatic giant cell tumor of spine. Summary of Background Data. Interferon alfa served as angiogenesis inhibitor and has been successfully used to treat giant cell tumor of long bones and facial bones. Up to date, no report is found with regard to the use of interferon as a stand-alone treatment for unresectable, recurrent, and metastatic giant cell tumor originated from the spine. Methods. A 29-year-old woman with C1 and C2 giant cell tumor was treated by radiotherapy, intralesional curet, and chemotherapy orderly. Tumor recurred after 2 years. A second curet was undertaken. Tumor recurred second time and caused severe spinal cord compression. Lung metastasis was diagnosed simultaneously. A 24-year-old man with recurrent giant cell tumor of T5 and T6 was treated by spondylectomy of T5 and T6. Six months later, a giant metastatic lesion was found in sacrococcygeal region, which was excised and proved to be giant cell tumor of bone. Four months later, 2 recurrent lesions were found beside the rectum. Interferon alfa-2b at a dose of 3,000,000 U/m2 was then administered subcutaneously everyday for both patients for 3.5 and 3 years, respectively. Results. No major complications related to the use of interferon occurred. The lesion in C1-C2 of the first patient regressed steadily and was restricted and encircled within the lateral mass. The metastatic lesions in the lungs also significantly reduced. The pararectal lesions of the second patient disappeared completely. Conclusion. Interferon therapy may be an effective and safe treatment for spine giant cell tumor recurrence and metastasis in soft tissue. The effectiveness may be time and dosage dependent.

in Vivo Study of a Self-stabilizing Artificial Vertebral Body Fabricated by Electron Beam Melting

Study Design. In vivo assessment of a novel artificial vertebral body fabricated by electron beam melting (EBM) for cervical vertebral body replacement in a sheep model. Objective. To investigate the feasibility of a novel artificial vertebral body: a “self-stabilizing artificial vertebral body” (SSAVB) fabricated by EBM in a sheep model. Summary of Background Data. Artificial vertebral body is widely used for vertebral body replacement and spinal fusion, but research on an artificial vertebral body fabricated by EBM has not been reported. Methods. An SSAVB made of porous Ti6Al4V was implanted into a sheep cervical spine to replace the C4 vertebral body for 6 and 12 weeks. Bone ingrowth and implant stability were radiologically evaluated, and histological and biomechanical tests were performed. Results. No screw loosening, implant dislocation, or bone fractures occurred during the experimental period. A significant difference (P = 0.001) in bone ingrowth between the 6- and 12-week groups was noted. Comparison of the range of motion of C3–C5 segments between the in vivo group and the control groups (intact C2–C6 segment and fresh sheep cervical spines from C2 to C6 segments that underwent C4 subtotal corpectomy with the posterior vertebral wall retention by SSAVB implantation) suggests that the implant can stably replace this area of the cervical spine. Conclusion. The open porous structure of Ti6Al4V fabricated by EBM facilitated bone ingrowth and the SSAVB can maintain cervical spine stability of the sheep. A porous metal implant can be used for load-bearing applications in a sheep model. It is hoped that these results will stimulate further study in human. Level of Evidence: 4

The frequency and treatment of dural tears and cerebrospinal fluid leakage in 266 patients with thoracic myelopathy caused by ossification of the ligamentum flavum.

Study Design. Retrospective review. Objective. To perform a single-institution analysis of incidence, treatment, and clinical outcome in patients with thoracic ossification of the ligamentum flavum (OLF) who experienced dural tears and cerebrospinal fluid (CSF) leakage. Summary of Background Data. There is a paucity of clinical reports focusing on dural tears and CSF leakage after thoracic OLF surgery. Because dural adhesion and dural ossification are common features of thoracic OLF, the incidence of CSF leakage in OLF patients is high and represents a significant clinical challenge. Methods. A total of 266 patients with thoracic OLF were admitted to our hospital from 1995 to 2011. Each patients medical records were reviewed to identify cases of dural tears and CSF leakage. Information on therapeutic strategy used to repair the dural tears and complications related to CSF leakage was extracted. Results. The incidence of dural tears and CSF leakage in OLF patients was 32% (85/266). The incidence of dural ossification was 25.2%. The dural tears were repaired with a range of materials, including gelatin sponge, muscle/fascia, artificial dura, silk suture, and fibrin glue. The intraoperative repair procedure did not resolve CSF leakage in 65 cases, and 16 of those cases experienced complications related to the continued CSF leakage, including CSF pseudocyst, wound dehiscence, and meningitis. Fifty-eight patients with CSF leakage were eventually cured by a series of comprehensive treatments, which included prone position, continuous pressure by sandbag, ultrasound-guided puncture, and aspiration. Only 7 patients required reoperation. Conclusion. Dural ossification was the main reason for dural tears. In all, 78 of the 85 patients with CSF leakage or dural tear were successfully cured. The success rate was 91.8%, which indicated that a series of comprehensive treatments was an effective strategy to treat these patients.

Enhanced angiogenesis and osteogenesis in critical bone defects by the controlled release of BMP-2 and VEGF: implantation of electron beam melting-fabricated porous Ti6Al4V scaffolds incorporating growth factor-doped fibrin glue.

Electron beam melting (EBM)-fabricated porous titanium implants possessing low elastic moduli and tailored structures are promising biomaterials for orthopedic applications. However, the bio-inert nature of porous titanium makes reinforcement with growth factors (GFs) a promising method to enhance implant in vivo performance. Bone-morphogenic protein-2 (BMP-2) and vascular endothelial growth factor (VEGF) are key factors of angiogenesis and osteogenesis. Therefore, the present study is aimed at evaluating EBM-fabricated porous titanium implants incorporating GF-doped fibrin glue (FG) as composite scaffolds providing GFs for improvement of angiogenesis and osteogenesis in rabbit femoral condyle defects. BMP-2 and VEGF were added into the constituent compounds of FG, and then this GF-doped FG was subsequently injected into the porous scaffolds. In five groups of implants, angiogenesis and osteogenesis were evaluated at 4 weeks post-implantation using Microfil perfusion and histological analysis: eTi (empty scaffolds), cTi (containing undoped FG), BMP/cTi (containing 50 μg rhBMP-2), VEGF/cTi (containing 0.5 μg VEGF) and Dual/cTi (containing 50 μg rhBMP-2 and 0.5 μg VEGF). The results demonstrate that these composite implants are biocompatible and provide the desired gradual release of the bioactive growth factors. Incorporation of GF delivery, whether a single factor or dual factors, significantly enhanced both angiogenesis and osteogenesis inside the porous scaffolds. However, the synergistic effect of the dual factors combination was observable on angiogenesis but absent on osteogenesis. In conclusion, fibrin glue is a biocompatible material that could be employed as a delivery vehicle in EBM-fabricated porous titanium for controlled release of BMP-2 and VEGF. Application of this method for loading a porous titanium scaffold to incorporate growth factors is a convenient and promising strategy for improving osteogenesis of critical-sized bone defects.

Prognostic significance of downregulated expression of programmed cell death 5 in chondrosarcoma.

Programmed Cell Death 5 (PDCD5) is a novel apoptosis‐related gene and deregulation of PDCD5 is involved in tumorigenicity. This study was designed to investigate the expression level of PDCD5 and to clarify its clinical significance in chondrosarcoma.

Increased levels of hypoxia-inducible factor-1α are associated with Bcl-xL expression, tumor apoptosis, and clinical outcome in chondrosarcoma

Hypoxia‐inducible factor (HIF)‐1α is a key nuclear transcription factor that regulates the cellular response to hypoxia, and is important for solid tumor growth and survival. However, the underlying role of HIF‐1α in human chondrosarcoma has not been well characterized. This study aims to investigate the expression patterns of HIF‐1α in chondrosarcoma, and its association with clinicopathologic features, Bcl‐xL expression, apoptosis index (AI), and overall survival of patients with chondrosarcoma. Our results shown that the protein levels of HIF‐1α were increased, and the mRNA and protein levels of Bcl‐xL were also increased in SW1353 cells under hypoxic conditions. In eight patients with chondrosarcoma, increased expression of HIF‐1α and Bcl‐xL was detected in chondrosarcoma tissues compared with the paired adjacent normal tissues. Of 34 archival specimens of chondrosarcomas, 20 (58.8%) showed high HIF‐1α protein expression as compared to benign cartilage tumors. Increased HIF‐1α expression was correlated with a higher pathological grade and MSTS stage of chondrosarcoma. Moreover, HIF‐1α expression was significantly associated with Bcl‐xL expression and AI. More significantly, the survival rate of patients with HIF‐1α high tumors was significantly lower than that of patients with HIF‐1α low tumors. These findings suggest that increased HIF‐1α levels mediated up‐regulation of Bcl‐xL play a prominent role in evasion of apoptosis and tumor progression, and can be predictive for the prognosis in human chondrosarcoma.

Differential proteomic profiling of chordomas and analysis of prognostic factors

The recurrence rate of chordoma is high, and the prognosis is poor.

Clinical Features of Thoracic Spinal Stenosis-associated Myelopathy: A Retrospective Analysis of 427 Cases.

Study Design:This was a retrospective review. Objective:The aim of this study was to examine the epidemiological characteristics and causes of spinal cord compression in thoracic spinal stenosis (TSS). Summary of Background Data:As the thoracic spinal canal is relatively narrow and the thoracic cord has a poor blood supply, severe neurological symptoms may develop if TSS is not treated promptly. However, as it is rare, TSS is less often studied and its clinical features are often not recognized. Methods:Between 2005 and 2012, 427 patients diagnosed with TSS underwent surgery in our department. The male to female ratio was 1.4:1. The mean age was 53 years. The most reported symptom was motor deficit in the lower extremities (347 cases, 81%), followed by sensory deficit in the lower limbs (271 cases, 64%). Falls were the most common trigger of acute symptoms (29 cases, 7%). Preoperative imaging results of each case were reviewed to summarize the causes and site of cord compression and coexisting spinal diseases. Results:The most reported compressive factor was ossification of the ligamentum flavum (OLF), which implicated in 309 cases, followed by thoracic disk herniation (TDH) and ossification of the posterior longitudinal ligament (OPLL). The most common site of OLF and TDH was T9–L1 (56% and 89%, respectively), whereas OPLL was mainly found at T1–8 (90%). Forty-seven patients (11%) had coexisting lumbar spinal disease and 64 (15%) had cervical disease. Conclusions:Onset of TSS was generally insidious but may be triggered acutely by apparently trivial events. Myelopathy mainly affected the lower limbs. The most common cause was OLF in the lower thoracic spine. Cervical or lumbar spinal disease was often also evident; therefore, comprehensive clinical assessment is required to avoid delays in diagnosis and treatment.