Maolin He

Anterior debridement, decompression, bone grafting, and instrumentation for lower cervical spine tuberculosis

BACKGROUND CONTEXT Cervical spine tuberculosis (TB) is uncommon, accounting for 3% to 5% of spinal TB. Although the development of anti-TB chemotherapy decreases the mortality rate significantly, it may not be applicable for all situations, especially for those with risk of instability, progression of neurologic deficit, and failure of medical treatment. PURPOSE To evaluate the efficacy of anterior instrumentation after debridement and bone grafting in patients with lower cervical TB over a 5-year period at a single institution. STUDY DESIGN A retrospective study examining the results of anterior debridement, decompression, bone grafting, and instrumentation for lower cervical spine TB. PATIENT SAMPLE The procedure was performed in 25 patients. OUTCOME MEASURES The clinical outcomes of infection activity, deformity, pain, and neurologic function were evaluated using erythrocyte sedimentation rate value and C-reactive protein value, kyphotic angle, visual analog scale pain score, and Frankel grade, respectively. METHODS Between 2005 and 2010, 25 patients (18 males and seven females; average age, 39 years) with lower cervical spine tuberculosis (C3-C7) underwent anterior debridement, decompression, bone grafting, and instrumentation. The average follow-up period was 37.4 months (range 24-57 months). The medical records and radiographic findings of the patients were reviewed. RESULTS There were three patients who had involvement of one vertebra, 18 had two vertebrae of involvement, and four had three vertebrae of involvement. Before surgery, there were three patients with Frankel grade B, five with grade C, 12 with grade D, and five with grade E. During the last follow-up examination, in 20 patients with neurological deficit, 11 patients improved one grade, six patients improved two grades, one patient improved three grades, and the neurologic status remained unchanged in two patients. Stable bone union was observed in all cases and the average time required for fusion was 6.8 months. The kyphosis Cobb angle improved from the preoperative average of 15.48° (range 0°-55°) to a postoperative average of -4.8° (range -12° to 4°) and there was no significant correction loss during the follow-up period. During the follow-up period, there were no grafts or instrumentation-related stabilization problems. There was no other recurrence of TB infection. CONCLUSIONS Anterior debridement, decompression, bone grafting, and instrumentation are safe and effective methods in the surgical management of lower cervical spine tuberculosis.

PIK3CA and AKT Gene Polymorphisms in Susceptibility to Osteosarcoma in a Chinese Population

PURPOSE To explore the association between PIK3CA and AKT single nucleotide polymorphisms(SNP) and osteosarcoma susceptibility. METHODS TaqMan polymerase chain reaction(PCR) was used to detect the genotypes of SNPs (rs7646409, rs6973569 and rs9866361) in peripheral blood samples from 59 patients with osteosarcoma and from 63 healthy controls. Unconditional logistic regression was used to analyze the correlation between SNPs and osteosarcoma risk. RESULTS No statistically significant difference was found between osteosarcoma patients and healthy controls in the genotype of AKT rs6973569 (P = 0.7). However, after stratified analysis, the genotype AA of AKT rs6973569 carried a higher risk of osteosarcoma metastasis (OR:2.94, 95%CL:1.00-8.59); the difference of rs7646409 genotype distributions between the case and control groups was statistically significant (P = 0.032). Taking genotype TT as a reference, the risk of osteosarcoma increased three fold in patients with genotype CC (OR:3.47, 95%CL:1.26-9.56). A statistically significant difference was found between the alleles C and T (P=0.005). Further analysis showed that the risk factor was more pronounced in male patients with Ennekings stage IIB and osteoblastic osteosarcoma. PIK3CA rs9866361 did not fit Hardy-Weinberg equilibrium (P < 0.05). CONCLUSIONS Genotype CC in locus PIK3CA rs7646409 may increase the risk of osteosarcoma in the Chinese population.

COL1A1 polymorphism is associated with risks of osteosarcoma susceptibility and death.

Osteosarcoma is a life-threatening malignancy that often occurs in teenagers. Collagen type I alpha 1 (COL1A1) polymorphism is reportedly associated with the occurrence of several human diseases. However, the relationship between COL1A1 and osteosarcoma occurrence remains unknown, and there is no report about the prevalence of COL1A1 in osteosarcoma. The purpose of this study is to investigate the associations of COL1A1 polymorphism with the susceptibility and survival of osteosarcoma. The relative risk to develop osteosarcomas and the overall survival associated to COL1A1 polymorphism were investigated in a homogeneous group of 189 osteosarcomas patients. Correlations with overall survival and hazard ratios (HR) were also analyzed. CT genotype and C allele of COL1A1 at rs1061970, and CG genotype and G allele of COL1A1 at rs2075559 are associated with decreased susceptibility to osteosarcoma in the Chinese population. CC genotype and C allele of COL1A1 at rs1061970 are associated with nonmetastasis in patients. CC genotype and CT genotype of COL1A1 at rs1061970 are associated with lower risk of death. Metastasis was found to be an independent prognostic factor for survival. This study provides the first evidence for the association between COL1A1 polymorphism and osteosarcoma risk in Chinese and shows that COL1A1 polymorphism at rs1061970 has a prognostic value for overall survival in osteosarcoma patients.

Highly expressed ribosomal protein L34 indicates poor prognosis in osteosarcoma and its knockdown suppresses osteosarcoma proliferation probably through translational control

Osteosarcoma has devastating health implications on children and adolescents. However, due to its low incidence and high tumor heterogeneity, it is hard to achieve any further improvements in therapy and overall survival. Ribosomal protein L34 (RPL34) has been increasingly recognized to promote the proliferation of malignant cells, but its role in osteosarcoma has not been investigated. In this study, real-time quantitative PCR (RT-qPCR) and immunohistochemistry revealed that RPL34 was highly expressed in osteosarcoma tissues when compared to adjacent tissues and normal bone tissues. Survival analysis showed that high expression of RPL34 predicted a poor prognosis for osteosarcoma patients. Knockdown of RPL34 in Saos-2 cells via lentivirus-mediated small interfering RNA (siRNA) significantly inhibited cell proliferation, induced cell apoptosis and G2/M phase arrest. Moreover, screening of transcription factors using University of California Santa Cruz (UCSC) Genome Browser, protein-protein interaction (PPI) network analysis, Gene Ontology (GO) and pathway enrichment analysis revealed that MYC participates in the transcriptional regulation of RPL34, which interacts with the subunits of eukaryotic translation initiation factor 3 (eIF3) and probably involves the translational control of growth-promoting proteins. Our findings suggest that RPL34 plays an important role in the proliferation of osteosarcoma cells.

Meta-analysis of Associations of the Ezrin Gene with Human Osteosarcoma Response to Chemotherapy and Prognosis

Various studies examining the relationship between Ezrin overexpression and response to chemotherapy and clinical outcome in patients with osteosarcoma have yielded inconclusive results. We accordingly conducted a meta-analysis of 7 studies (n = 318 patients) that evaluated the correlation between Ezrin and histologic response to chemotherapy and clinical prognosis (death). Data were synthesized in receiver operating characteristic curves and with fixed-effects and random-effects likelihood ratios and risk ratios. Quantitative synthesis showed that Ezrin is not a prognostic factor for the response to chemotherapy. The positive likelihood ratio was 0.538 (95% confidence interval [95% CI], 0.296- 0.979; random-effects calculation), and the negative likelihood ratio was 2.151 (95% CI, 0.905- 5.114; random-effects calculations). There was some between-study heterogeneity, but no study showed strong discriminating ability. Conversely, Ezrin positive status tended to be associated with a lower 2-year survival (risk ratio, 2.45; 95% CI, 1.26-4.76; random-effects calculation) with some between-study heterogeneity that disappeared when only studies that employed immunohistochemistry were considered (risk ratio, 2.97; 95% CI, 2.01- 4.40; fixed-effects calculation). To conclude, Ezrin is not associated with the histologic response to chemotherapy in patients with osteosarcoma, whereas Ezrin positivity was associated with a lower 2-year survival rate regarding risk of death at 2 years. Expression change of Ezrin is an independent prognostic factor in patients with osteosarcoma.

Outcomes and Treatment of Lumbosacral Spinal Tuberculosis: A Retrospective Study of 53 Patients

Study Strategy A retrospective clinic study. Purpose To evaluate the efficacy of conservative and surgical treatment for lumbosacral tuberculosis. Methods This study retrospectively reviewed 53 patients with lumbosacral tuberculosis who were treated in our institution between January 2005 and January 2011. There were 29 males and 24 females with average ages of 37.53 ± 17.28 years (range 6–72 years). 11 patients were given only anti-TB drugs; the remainder underwent anterior debridement, interbody fusion with and without instrumentation, or one-stage anterior debridement combined with posterior instrumentation. Outcome data for these patients included neurologic status, lumbosacral angle, erythrocyte sedimentation rate value(ESR) and C-reactive protein value(CRP) were assessed before and after treatment. Results The mean lumbosacral angles were 23.00°± 2.90°in the conservatively treated patients and 22.36°± 3.92o in the surgically treated patients. At the final follow-up, this had improved to 24.10o ± 2.96°in the conservatively treated patients and 28.13° ± 1.93°in the surgically treated patients (all P < 0.05). There were statistically significant differences before and after treatment in terms of ESR and CRP (all P < 0.05). All patients achieved bone fusion. The mean follow-up period was 32.34 ± 8.13 months (range 18 to 55 months). The neurological deficit did not worsen in any of the patients. Conclusions It has been proven that conservative and surgical treatments are safe and effective and produce good clinical outcomes for patients with lumbosacral tuberculosis. The advantages of operation include thoroughness of debridement, decompression of the spinal cord, and adequate spinal stabilization.

Quantitative assessment of the association of COX-2 (Cyclooxygenase-2) immunoexpression with prognosis in human osteosarcoma: a meta-analysis.

Background Numerous studies examining the relationship between Cyclooxygenase-2 (COX-2) immunoexpression and clinical outcome in osteosarcoma patients have yielded inconclusive results. Methods We accordingly conducted a meta-analysis of 9 studies (442 patients) that evaluated the correlation between COX-2 immunoexpression and clinical prognosis (death). Pooled odds ratios (OR) and risk ratios (RR) with 95% confidence intervals (95% CI) were calculated using the random-effects or fixed-effects model. Results Meta–analysis showed no significant association between COX-2 positivity and age, gender, tumor location, histology, stage, metastasis or 90% necrosis. Conversely, COX-2 immunoexpression was associated with overall survival rate (RR=2.12; 95% CI: 1.10–3.74; P=0.009) and disease-free survival rate (RR=1.63; 95% CI: 1.17–2.28; P=0.004) at 2 years. Sensitivity analysis performed by omitting low quality studies showed that the pooled results were stable. Conclusions COX-2 positivity was associated with a lower 2-year overall survival rate and disease-free survival rate. COX-2 expression change is an independent prognostic factor in patients with osteosarcoma.

The association of glutathione S-transferase polymorphisms in patients with osteosarcoma: evidence from a meta-analysis.

Osteosarcoma is a life-threatening malignancy that often occurs in teenagers. Numerous studies have reported glutathione S-transferase polymorphisms are associated with osteosarcoma, but the results are inconclusive, partially because the sample size in each of published studies is relatively small. Therefore, we performed a meta-analysis of the published studies to estimate the association more accurately. To preciously examine the association between the glutathione S-transferase polymorphisms and osteosarcoma, we undertook a meta-analysis of six case-control studies. The association between the glutathione S-transferase polymorphisms and osteosarcoma risk was assessed by odds ratios together with their 95% confidence intervals using a fixed-effects model or random-effects model. In addition, hazard ratio was used to measure the relationship between glutathione S-transferase polymorphisms and prognosis in patients with osteosarcoma. We found that there was significant association between the polymorphisms in GSTT1 or GSTM3 (AA versus BB) and osteosarcoma risk. In addition, there is no evidence of association on GSTM1, GSTT1, GSTP1 (IIe/IIe versus IIe/Val) or GSTP1 (IIe/IIe versus Val/Val) polymorphisms with prognosis in osteosarcoma. In conclusion, the GSTT1 and GSTM3 polymorphisms might influence osteosarcoma risk.

Rho GTPase-Activating Protein 35 rs1052667 Polymorphism and Osteosarcoma Risk and Prognosis

The Rho GTPase-activating protein 35 (ARHGAP35), an important Rho family GTPase-activating protein, may be associated with tumorigenesis of some tumors. Here, we investigated the relationship between an important polymorphic variant at 3′-UTR of this gene (rs1052667) and osteosarcoma risk and prognosis. This hospital-based case-control study, including 247 osteosarcoma patients and 428 age-, sex-, and race-matched healthy controls, was conducted in Guangxi population. Genotypes were tested using TaqMan PCR technique. We found a significant difference in the frequency of rs1052667 genotypes between cases and controls. Compared with the homozygote of rs1052667 C alleles (rs1052667-CC), the genotypes with rs1052667 T alleles (namely, rs1052667-CT or -TT) increased osteosarcoma risk (odds ratios: 2.41 and 7.35, resp.). Moreover, rs1052667 polymorphism was correlated with such pathological features of osteosarcoma as tumor size, tumor grade, and tumor metastasis. Additionally, this polymorphism also modified the overall survival and recurrence-free survival of osteosarcoma cases. Like tumor grade, ARHGAP35 rs1052667 polymorphism was an independent prognostic factor influencing the survival of osteosarcoma. These results suggest that ARHGAP35 rs1052667 polymorphism may be associated with osteosarcoma risk and prognosis.

Association of GRM4 gene polymorphisms with susceptibility and clinicopathological characteristics of osteosarcoma in Guangxi Chinese population

Osteosarcoma is the most frequent malignant primary bone tumor. GRM4 is expressed in human osteosarcoma cells, and high expression of mGluR4 in osteosarcoma tissues is related to poor prognosis. The aim of this study was to investigate the association between polymorphism of the GRM4 gene and the susceptibility to osteosarcoma in a Chinese population. In a case–control study, we investigated polymorphisms in the GRM4 gene (rs2229901, rs733457, and rs1906953) with a real-time quantitative polymerase chain reaction (PCR) assay (TaqMan). The study was conducted with 126 Chinese patients with osteosarcoma and 168 Chinese subjects in a control group. Unconditional logistic regression was used to analyze the correlation between single nucleotide polymorphisms (SNPs) and osteosarcoma risk. Different survival rates of different genotypic patients with osteosarcoma were analyzed through Kaplan–Meier. There were statistically significant differences in the distributions of the rs1906953 genotypes between the cases and control group (P = 0.034). However, there was no remarkable difference in the three genotypes of GRM4 gene rs2229901 locus between the patient group and control group (P = 0.369). Survival analysis for rs1906953 showed that the median survival time of osteosarcoma patients with the CC genotype was significantly shorter compared to the CT and TT genotypes; patients carrying CC genotype have apparently got a decrease in their recurrence-free survival time in comparison with patients carrying TT genotype. Our data suggest that GRM4 gene polymorphism is closely related to the morbidity and metastasis of osteosarcoma in a Chinese population.