Neo-adjuvant radiation and intratumoral immunotherapy followed by surgery-NARIS trial for extremity soft tissue sarcoma.

Extremity soft tissue sarcoma (ESTS) is a rare malignant nonepithelial disease, calling for combined modality treatments with surgery to further improve local control rates and long-term survival, especially in patients with multiple local recurrences with or without risk of amputation. In this double-arm, open-label, Phase II clinical trial, we will enroll 30 patients with pathologically confirmed ESTS without nodal involvement or distant metastases. Patients are randomly assigned to the combination treatment group or the radiation monotherapy group. Additionally, tumor and biological samples will be obtained directly before and after neoadjuvant therapy, allowing for studies of immune response and primary drug resistance mechanisms.Clinical Trial Registration: ChiCTR2200060659 (http://www.chictr.org.cn) (ClinicalTrials.gov).

[Box: see text].

An interactive dose optimizer based on population pharmacokinetic study to guide dosing of methotrexate in Chinese patients with osteosarcoma.

PURPOSE: Osteosarcoma is a rare tumor with an incidence of 4.4 cases per million per year in adolescent. High-dose methotrexate (HD-MTX) is the standard first-line chemotherapeutic agent for osteosarcoma. However, its efficacy can vary significantly among individuals due to wide pharmacokinetic variability. Despite this, only a few population pharmacokinetics (popPK) models based on Chinese patients with osteosarcoma have been reported. Thus, this study aimed to develop a HD-MTX popPK model and an individual model-based dose optimizer for osteosarcoma therapy. METHOD: A total of 680 MTX serum concentrations from 57 patients with osteosarcoma were measured at the end of MTX infusion and 10 h, 24 h, 48 h, and 72 h after the start of infusion. Using the first-order conditional estimation method with NONMEM, a popPK model was estimated. Goodness-of-fit plots, visual predictive checks, and bootstrap analysis were generated to evaluate the final model. A dose optimizer tool was developed based on the validated models using R Shiny. Additionally, clinical data from 12 patients with newly diagnosed osteosarcoma were collected and used as the validation set to preliminarily verify the predictive ability of the popPK model and the dose optimizer tool. RESULTS: Body surface area (BSA) was the most significant covariate for compartment distribution. Creatinine clearance (CrCL) and co-administration of NSAIDs were introduced as predictors for central compartmental and peripheral compartmental clearance, respectively. Co-administration of NSAIDs was associated with significantly higher MTX concentrations at 72 h (p = 0.019). The dose optimizer tool exhibited a high consistency in predicting MTX AUC compared to the actual AUC (r = 0.821, p < 0.001) in the validation set. CONCLUSION: The dose optimizer tool could be used to estimate individual PK parameters, and optimize personalized MTX therapy in particular patients.

[Surgical management of sacral neurogenic tumors].

OBJECTIVE: To observe the efficacy and complications of one-stage tumor resection to treat primary sacral neurogenic tumors and to discuss some details in the clinically relevant anatomy. METHODS: A retrospective analysis of 26 patients with neurogenic turors of the sacral spine who were surgically treated from January 2001 to January 2018, including 16 males and 10 females, aged from 21 to 69 years old with an average age of (39.3±10.9) years old. The courses of diseases ranged from 3 to 56 months with an average of (17.9±10.1) months. The diameters of presacral components ranged from 3.3 to 19.6 cm with an average of (8.7±4.1) cm. The proximal margin of presacral lesions was above the L5S1 level in 6 cases, and lower than L5S1 in 20 cases. A posterior incision approach for one-stage complete resection of the tumor was used firstly, and an anterior approach was combined when necessary. Spinal-pelvic reconstruction with the modified Galveston technique was also carried out in relevant cases. Whether to preserve the tumor-involved nerve roots depended on the situation during the operation. The operation time, intraoperative blood loss, pain relief, and complications were recorded. The lumbosacral spine stability and sacral plexus neurological function were evaluated during postoperative follow-up, and local recurrence and distant metastasis were examined as well. RESULTS: Total excision was achieved in all 26 patients, with an operation time of (160.4±35.3) mins and an intraoperative blood loss of (1 092.3±568.8) ml. Tumors have been removed via a posterior-only approach in 21 cases and via combined anterior/posterior approaches in 5 cases. The diameter of presacral masses components ranged from 11.3 to 19.6 cm with an average of (15.1±3.2) cm in patients with combined anterior/posterior approaches, and ranged from 3.3 to 10.9 cm with an average of (7.2±2.4) cm in patients with a posterior-only approach. Five of the six patients whose proximal margin of presacral masses was above the L5S1 level adopted combined anterior/posterior approaches, and 20 patients lower than the L5S1 level adopted the posterior-only approach. All the patients were followed up for 6 to 82 months with an average of(45.4±18.2)months. Postoperative lumbosacral pain and lower extremity radicular pain were significantly relieved, and sensation, muscle strength and bowel and bladder function were also improved to varying degrees. The postoperative early complications included superficial wound infection in 1 case and cerebrospinal fluid leakage in 2 cases. Pathology confirmed 17 cases of schwannoma, 7 cases of neurofibroma and 2 cases of malignant schwannoma. Local recurrence was observed in two cases of benign neurogenic tumors. One patient with a malignant nerve sheath tumor had lung metastasis, who died 20 months after the operation. In 17 cases of upper sacral neurogenic tumors, 4 cases did not undergo spinal-pelvic reconstruction with internal fixation, of which 2 cases suffered from postoperative segmental instability. Tumor-involved nerve roots were resected during surgery in 7 cases. One of these patients who had S2 and S3 nerve roots sacrificed simultaneously had an impaired bladder and bowel function postoperatively, and did not recover completely. In the other 6 cases, the neurological function was not damaged obviously or recovered well. CONCLUSION: The posterior approach can directly expose the lesions, and it is also convenient to deal with nerve roots and blood vessels. The operation time, intraoperative blood loss, degree of symptom relief, complication rate, and recurrence and metastasis rate can be controlled at an appropriate level. It is a safe and effective surgical approach. When the upper edge of the presacral mass is higher than the L5S1 level or the diameter of the presacral mass exceeds 10 cm, an additional anterior approach should be considered. The stress between the spine and pelvis is high, and internal fixation should be used to restore the mechanical continuity of the spine and pelvis during resection of neurogenic tumors of the high sacral spine. Most of the parent nerve roots have lost their function. Resection of a single parent nerve root is unlikely to cause severe neurological dysfunction, while the adjacent nerve roots have compensatory functions and should be preserved as much as possible during surgery.

Sensitive osteosarcoma diagnosis through five-base telomerase product-triggered CRISPR-Cas12a enhanced rolling circle amplification.

Osteosarcoma is the most frequent primary malignant bone tumor, composed of mesenchymal cells producing osteoid and immature bone. The sensitive detection of telomerase plays a pivotal role in the early diagnosis and therapeutic treatment of osteosarcoma. We report here an in vitro strategy for sensitive telomerase activity detection through the integration of rolling circle amplification (RCA) and a clustered regularly spaced short palindrome repeats (CRISPR)-Cas12a system. In the proposed strategy, telomerase substrate (TS) primers are easily controlled to extend five bases (GGGTT) to give short telomerase extension products (TEP) with definite lengths without adding dATP. The resulting short TEPs can then cyclize the padlock through hybridizing with its two terminals and thus initiate the following RCA. To obtain an improved sensitivity, the CRISPR-Cas12a system is attached to collaterally cut surrounding DNA reporter probes after recognizing the target single strand DNA sequence in the RCA products. The highlights of this strategy are as follows: (i) the short TEP triggered strategy is excellent at detecting low telomerase activity and thus contributes to the early diagnosis of malignant tumors; (ii) highly sensitive telomerase activity detection which is easy to operate from RCA initiated CRISPR-Cas12a; (iii) opening up of a new avenue for telomerase activity detection with a CRISPR-Cas12a system. Finally, the proposed strategy exhibited sensitive telomerase activity detection under optimized experimental parameters and has great application potential for the clinical diagnosis of malignant tumors and the development of anti-cancer drugs.

Management of Apatinib-Related Adverse Events in Patients With Advanced Osteosarcoma From Four Prospective Trials: Chinese Sarcoma Study Group Experience.

Four prospective trials have reported apatinib-related efficacy in osteosarcoma, with a high response rate of 43.2%. Currently, Adverse Events (AEs) have increasingly gained attention, as treatment with multiple tyrosine kinase inhibitors (TKIs) is potentially lifelong. For this reason, a consensus meeting of the Chinese Sarcoma Study Group (CSSG), which is a multidisciplinary panel composed of pediatric, medical and surgical oncologists specializing in sarcoma, nurse specialists, oncological senior pharmacists and gastroenterologists, was held to develop comprehensive guidelines on AEs emerging due to apatinib treatment to better assist in the prevention, management, and understanding of AE development. We summarized all AEs that arose in ≥10% of the participants as well as rare AEs that required extra caution to prevent that were observed in these four published prospective trials and arranged these AEs into 14 disorder systems according to CTCAE 5.0. In this review, we discuss strategies for the management of AEs in patients with advanced osteosarcoma, with the aim of maximizing treatment benefits and minimizing the need for apatinib treatment discontinuation. We also focus on providing recommendations for the prophylaxis and treatment of advanced osteosarcoma using apatinib to achieve optimal outcomes.

Survival outcomes of patients with brain metastasis of osteosarcoma can be improved by aggressive multi-disciplinary interventions including chemotherapy.

BACKGROUND/OBJECTIVE: Brain metastasis in osteosarcoma (BMO) is rare and its clinical characteristics are often buried among studies on brain metastasis of bone and soft tissue sarcomas. The aim of the present study was to summarize the incidence, clinical characteristics, treatment and outcomes of patients with BMO. METHODS: This retrospective study included 7 patients with BMO who received treatment in our center between 2005 and 2019. The clinical medical records of the 7 patients, together with data of 70 BMO patients published in 33 articles and retrieved by means of PubMed and Medline, were analyzed, retrospectively. RESULTS: Data analysis of the 97 BMO patients showed a high correlation between the interval from the primary diagnosis to BMO occurrence and the interval from the primary diagnosis to prior metastases. Multivariate analysis showed that chemotherapy, radiotherapy and surgery were three main factors affecting the overall survival of BMO patients (HR = 0.427; HR = 0.372; HR = 0.296). Surgery combined with chemotherapy or radiotherapy offered a better overall survival than surgery alone. CONCLUSION: Patients with BMO may obtain survival benefits from regular neuroimaging and early aggressive multi-disciplinary interventions including surgical resection, postoperative radiotherapy and chemotherapy. SYNOPSIS: This is a retrospective study describing the characteristics of metastasic intervals, locations, clinical features and prognosis in 97 patients with brain metastasis of osteosarcoma (BMO). Multivariate analysis showed that chemotherapy was effective as surgery and radiotherapy for the treatment of BMO. Our findings emphasize the importance of regular neuroimaging and early aggressive multi-disciplinary interventions including surgical resection, postoperative radiotherapy and chemotherapy.

Suppressing CHD1L reduces the proliferation and chemoresistance in osteosarcoma.

Osteosarcoma (OS) is the most common bone malignant tumor. However, the genetic basis of OS pathogenesis is still not understood, and occurrence of chemo-resistance is a major reason for the high morbidity of OS patients. Recently, chromodomain helicase/ATPase DNA binding protein 1-like gene (CHD1L) has been identified as a gene related to malignant tumor progression. Unfortunately, its effects on OS development and drug resistance are still not understood. In the study, we attempted to investigate the effects of CHD1L on tumorigenesis and chemoresistance in OS. We found that CHD1L expression was markedly up-regulated in OS samples, especially in cisplatin (cDDP)-resistant patients. We also showed that OS cells with CHD1L knockdown were more sensitive to cDDP treatment with lower IC50 values. In addition, we found that CHD1L deletion markedly reduced cell proliferation and induced apoptosis in OS cells with cDDP resistance. Moreover, the properties of cancer stem cells were highly suppressed in cDDP-resistant OS cells following CHD1L knockdown. Furthermore, multidrug resistance protein 1 (MDR-1) expression levels were dramatically decreased in OS cells with cDDP resistance when CHD1L was suppressed. Functional analysis indicated that CHD1L knockdown clearly restrained the activation of ERK1/2, protein kinase B (AKT) and NF-κB signaling pathways in cDDP-resistant OS cells. Consistently, animal experiments suggested that CHD1L suppression mitigated cDDP resistance in the generated in vivo xenografts. Collectively, CHD1L could modulate chemoresistance of OS cells to cDDP, and thus may be inspiring findings for overcoming drug resistance in OS.

Erratum: Focal adhesion kinase is involved in the migration of human osteosarcoma cells.

[This corrects the article DOI: 10.3892/ol.2015.3131.].

Clinical factors affecting prognosis of limb osteosarcoma in China: a multicenter retrospective analysis.

OBJECTIVE: This study was performed to explore the relationship between various clinical factors and the prognosis of limb osteosarcoma. METHODS: We retrospectively analyzed the clinical data of 336 patients with limb osteosarcoma treated from June 2000 to August 2016 at 7 Chinese cancer centers. Data on the patients' clinical condition, treatment method, complications, recurrences, metastasis, and prognosis were collected and analyzed. Kaplan-Meier analysis and Cox regression models were used to analyze the data. RESULTS: The patients comprised 204 males and 132 females ranging in age from 6 to 74 years (average, 21.1 years). The overall 3- and 5-year survival rates were 65.0% and 55.0%, respectively. The 5-year overall survival rate was 64.0% with standard chemotherapy and 45.6% with non-standard chemotherapy. Cox regression analysis demonstrated that standard chemotherapy, surgery, recurrence, and metastasis were independent factors associated with the prognosis of limb osteosarcoma. CONCLUSION: The survival of patients with limb osteosarcoma can be significantly improved by combining standard chemotherapy and surgery. The overall survival rate can also be improved by adding methotrexate to doxorubicin-cisplatin-ifosfamide triple chemotherapy.

Clinical Guideline for Microwave Ablation of Bone Tumors in Extremities.

Microwave ablation has been used to treat bone tumors in extremities for more than 30 years. With improved recognition, updated microwave equipment, and expanded clinical application, microwave ablation has recently been widely used to treat bone tumors. To standardize the application of microwave ablation in the clinical treatment of bone tumors in the limbs, research results and clinical experience involving the use of microwave ablation to treat bone tumors in the limbs have been summarized, and a clinical guideline has been designed. This guideline is aimed at providing a reliable clinical basis for indications, preoperative evaluation and decision-making, perioperative treatment, complications, and other issues via evidence-based medicine. Two aspects are considered-percutaneous microwave ablation and intraoperative microwave ablation of bone tumors in extremities. Ultimately, the guideline is intended to standardize treatment and improve the clinical efficacy of microwave ablation of bone tumors in extremities.

The CD24+ cell subset promotes invasion and metastasis in human osteosarcoma.

BACKGROUND: Osteosarcoma is the most common primary aggressive bone tumor affecting children and young adolescents. Metastases are often resistant to conventional chemotherapy and mean short-term survival. Development of valuable diagnostic indicators and targeting agents will have important implications for clinical diagnosis by the identification and characterization of molecules that contribute to its aggressive behavior. METHODS: We examined differential expression levels of common stem cell markers in osteosarcoma parental and sphere cells. In addition, we further analyzed the changes of candidate common stem cell markers before and after in vitro chemotherapy of osteosarcoma cells. The biological functions of CD24+ subpopulation in osteosarcoma such as proliferation, migration, invasion, tumorigenesis and metastasis were systematically investigated, and the correlations of CD24 levels with prognosis in patients with osteosarcoma were analyzed. FINDINGS: CD24+ Cells presented characteristics of TICs and resist drug-induced apoptosis. The prevention of tumor formation and metastasis by CD24 knockdown highlights the potential of CD24 as a therapeutic target for osteosarcoma. Moreover, the levels of CD24 in osteosarcoma samples were significantly correlated with the prognosis of patients. INTERPRETATION: CD24+ cell subset played an important role in osteosarcoma invasion and metastasis. FUNDING: National Natural Science Foundation of China (No.81772857); Shanghai Science and Technology Commission (18140902000); Shanghai Municipal Health Commission (2017ZZ01017; 17411950301).

miR-139 inhibits osteosarcoma cell proliferation and invasion by targeting ROCK1.

miR-139 has a tumor suppressor effect in many tumors. Here, we examined the suppressive role of this miRNA and its target, ROCK1, in osteosarcoma (OS), a highly malignant bone tumor that mainly affects children and adolescents. The expression of miR-139 was down-regulated in OS. Overexpression of miR-139 significantly inhibited OS cell proliferation, migration, and invasion. Ectopic expression of miR-139 down-regulated ROCK1, a target of miR-139, by direct binding to its 3' untranslated region (3'UTR). Direct  siRNA-mediated silencing of ROCK1 exerted an inhibitory effect on OS cell proliferation and invasion similar to the effect of miR-139. ROCK1 transfection reversed the suppressive effect of miR-139 on OS cell proliferation and invasion. Both miR-139 and siRNA knockdown of ROCK1 significantly down-regulated ß-CATENIN and p-AKT and up-regulated E-CADHERIN and p53. The data provided here show that miR-139 exerts suppressive effects on proliferation and invasion of OS cells by targeting ROCK1.

Expression profiling of long noncoding RNAs associated with vasculogenic mimicry in osteosarcoma.

Osteosarcoma (OS) is the most common highly malignant bone tumor in teens. Vasculogenic mimicry (VM) is defined as de novo extracellular matrix-rich vascular-like networks formed by highly aggressive tumor cells. We previously reported the presence of VM and it is an unfavorable prognostic factor in OS patients. Long noncoding RNAs (lncRNAs) are aberrantly expressed in OS and involved in cancer cell VM. However, lncRNAs in VM formation of OS have not been investigated. We, therefore, profiled the expression of lncRNAs in highly aggressive OS cell line 143B compared with its parental poorly aggressive cell line HOS. The differentially expressed (DE) lncRNAs and messenger RNA (mRNAs) were subjected to constructed lncRNA-mRNA coexpressed network. The top-ranked hub gene lncRNA n340532 knockdown 143B cells were used for in vitro and in vivo VM assays. The annotation of DE lncRNAs was performed according to the coexpressed mRNAs by Gene Ontology and pathway analysis. A total of 1360 DE lncRNAs and 1353 DE mRNAs were screened out. lncRNA MALAT1 and FTX, which have known functions related to VM formation and tumorigenesis were identified in our data. The coexpression network composed of 226 lncRNAs and 118 mRNAs in which lncRNA n340532 had the highest degree number. lncRNA n340532 knockdown reduced VM formation in vitro. The suppression of n340532 also exhibited potent anti-VM and antimetastasis effect in vivo, suggesting its potential role in OS VM and metastasis. Furthermore, n340532 coexpressed with 10 upregulation mRNAs and 3 downregulation mRNAs. The enriched transforming growth factor-ß signaling pathway, angiogenesis and so forth were targeted by those coexpressed mRNAs, implying n340532 may facilitate VM formation in OS through these pathways and gene functions. Our findings provide evidence for the potential role of lncRNAs in VM formation of OS that could be used in the clinic for anti-VM therapy in OS.

Isoliquiritigenin inhibits the proliferation, apoptosis and migration of osteosarcoma cells.

The overall survival rate of patients with osteosarcoma has remained unchanged for the last several decades. Therefore, novel drugs for osteosarcoma treatment are required. Isoliquiritigenin (ISL), a natural compound, has been demonstrated to inhibit the growth of various tumors. However, it is unclear whether ISL is able to inhibit the growth of osteosarcoma. In the present study, it was identified that ISL was able to inhibit the growth of the osteosarcoma cell line Saos­2 cells in vitro and in xenograft tumors primarily by attenuating tumor cell proliferation and, cell migration and promoting tumor cell apoptosis. Decreased tumor cell proliferation induced by ISL was associated with downregulation of cyclin D1 and upregulation of p53, p21 and p27. Increased tumor cell apoptosis triggered by ISL was associated with downregulation of apoptosis regulator Bcl­2, upregulation of apoptosis regulator Bax and damaged mitochondrial function evidenced by a low level of ATP­synthesis. In addition, ISL was able to inhibit the migratory capacity of Saos­2 cells by modulating the expression of matrix metalloproteinase (MMP)2 and MMP9. Mechanistic analysis revealed that the tumor growth­inhibitory effect of ISL may depend on the action of ISL on the phosphorylation of PI3K and AKT. However, it remains to be investigated whether the inhibitory effect of ISL on the migration of Saos­2 cells was associated with downregulated PI3K/AKT signaling. Overall, the present study provided evidence for the potential use of ISL against osteosarcoma.

Development and Validation of a Novel Survival Prediction Model in Patients With Spinal Metastasis From Non-small Cell Lung Cancer.

STUDY DESIGN: Retrospective study. OBJECTIVE: The aim of this study was to develop a model for predicting survival of patients with non-small cell lung cancer (NSCLC) spinal metastasis and compare its accuracy with the existing scoring systems. SUMMARY OF BACKGROUND DATA: Spinal metastasis is commonly seen in advanced NSCLC and usually associated with poor survival prognosis. METHODS: A total of 376 patients with NSCLC spinal metastases admitted to our institution from January 2010 to October 2016 were enrolled. They were randomly assigned at a 3:1 ratio to a training cohort (n = 282) and a validation cohort (n = 94). A nomogram for survival prediction was established by identifying and integrating significant prognostic factors, and then subjected to bootstrap validation in both training and validation cohorts. The discrimination was measured by concordance index (C-index). Predictive accuracy was compared with three existing models by the receiver-operating characteristic curve (ROC) and area under ROC in both training and validation cohorts. RESULTS: Six independent prognostic factors including sex (P = 0.008), the presence of visceral metastasis (P = 0.008), the number of metastases in the vertebral body (P = 0.011), Frankel score (P < 0.001), D-dimer (P = 0.002), and sensitive epidermal growth factor receptor mutation (p < 0.001) were identified and entered into the nomogram. The calibration curves for probability of 3-, 6-, 12- and, 24-month overall survival showed good agreement between the predictive risk and the actual risk. The C-index of the nomogram was 0.708 (95% confidence interval [CI], 0.674-0.742) in the training cohort and 0.683 (95% CI, 0.619-0.747) in the validation cohort. Model comparison showed that this nomogram had better predictive accuracy than the Tomita et al, Tokuhashi et al, and Schwab et al scoring systems (P < 0.05 in the training cohort). CONCLUSION: We established and validated a novel nomogram that could be used to predict the survival outcome of patients with NSCLC spinal metastasis, thus helping clinicians in decision making and individualized care planning of such patients. LEVEL OF EVIDENCE: 4.

Application of SRT plus MR recession in supra-maximal esotropia from chronic sixth nerve palsy.

BACKGROUND: To investigate prognostic factors in patients with augmented superior rectus transposition (SRT) for sixth nerve palsy. METHODS: Thirteen patients who were diagnosed with sixth nerve palsy and underwent augmented SRT between January 2015 and February 2017 in EENT Hospital of Fudan University were reviewed retrospectively. Data including age, sex, etiology of the abducens nerve palsy, degree of pre- and postoperative deviation in the primary position, pre- and postoperative abduction deficit, any induced vertical or torsional deviations, reoperations, and other complications was collected. Patients with undercorrection of SRT surgeries received additional inferior rectus transposition (IRT) surgery. RESULTS: Mean esodeviation in primary position improved from 81.92△ to 30.54△ (p < 0.001) with a 1.54-unit improvement in abduction (p = 0.001). Six patients achieved alignment defined as esodeviation in primary position within 10△ of orthotropia and seven patients were undercorrected after the first SRT surgery. Multivariable linear regression analysis showed that among factors (disease duration, preoperative esodeviation, preoperative abduction deficit), only the degree of preoperative abduction deficit (ß = - 13.68) was the prognostic factor for success of SRT surgery. After IRT procedures, the mean esodeviation in primary position improved from 40△ to 8△ (p < 0.01). CONCLUSION: The degree of preoperative abduction deficit is the prognostic factor for augmented SRT for sixth nerve palsy. Patients with worse abduction deficit have a greater likelihood of needing a secondary operation, and IRT could be a good choice for reoperation after SRT.

Migration-inducing gene-7 independently predicts poor prognosis of human osteosarcoma and is associated with vasculogenic mimicry.

Vasculogenic mimicry (VM) is a special type of vascular channel formed by tumor cells without endothelial cell participation. Migration-inducing gene 7 (MIG-7) plays an important role in regulating VM. In this study, immunohistochemical staining was used to detect MIG-7 in tissue specimens from 141 primary osteosarcoma patients, and the relationship between MIG-7 and VM was examined. Survival analysis were performed to evaluate the prognoses. MIG-7 knockdown osteosarcoma cells were used for cell proliferation, apoptosis, migration, invasiveness and VM formation assays. A spontaneously metastasizing cell line-derived orthotopic xenograft mouse model was established to evaluate the effect of MIG-7 knockdown on tumorigenesis, VM formation and lung metastasis. MIG-7 expression was associated with VM formation. There were significant differences in overall and metastasis-free survival between the MIG-7-positive and MIG-7-negative groups. The MIG-7 expression was shown to be an independent indicator of both overall and metastasis-free survival. In vitro knockdown of MIG-7 dramatically reduced migration, invasion and VM formation in osteosarcoma cells without any significant effect on cell proliferation and apoptosis. MIG-7 knockdown also exhibited potent antitumor, antimetastasis and anti-VM effects in the orthotopic mouse model of 143B osteosarcoma. Therefore, MIG-7 serves as an independent unfavorable prognostic indicator in osteosarcoma patients and MIG-7 is an important mediator of osteosarcoma VM formation.

Surgery option in the management of delayed diplopia after radiation therapy for nasopharyngeal carcinoma.

PURPOSE: Radiation therapy is a standard treatment for nasopharyngeal carcinoma. Diplopia due to radiation damage to the sixth nerve significantly erodes the patient's quality of life. This study investigated the effectiveness of extraocular surgery in the treatment of delayed diplopia caused by radiation therapy. METHODS: A retrospective case series of 16 patients (7 men and 9 women) with delayed diplopia after radiation therapy for nasopharyngeal carcinoma was enrolled in the study. Unilateral lateral rectus resection was performed under topical anesthesia. Follow-up time was more than 12 months. Outcome measures were prism diopter and self-reported symptoms. RESULTS: All patients diagnosed with sixth nerve palsy reported elimination of symptoms on postoperative day 1 without complications. One patient required a second procedure due to recurrence of symptoms. At 12-month follow-up, no patient reported recurrence of symptoms. The absolute horizontal deviation significantly decreased from a preoperative value of 16 prism diopter to a value of 1.5 prism diopter postoperatively (p < 0.001). CONCLUSION: These results suggest that unilateral lateral rectus resection under topical anesthesia is an effective treatment for delayed diplopia after radiation therapy for nasopharyngeal carcinoma. A large randomized prospective study to confirm these findings is warranted.

Development and proposal of a scoring system for giant cell tumour of the bone around the knee.

PURPOSE: The purpose of this study was to provide the surgeons with effective and reliable guidelines for surgical decision-making by establishing a scoring system for giant cell tumour (GCTSS) based on evidence and expert opinion. METHODS: The modified Delphi technique and analytic hierarchy process were used to establish the GCTSS. The GCTSS was defined and classified based on different surgical methods using data from 207 patients collected retrospectively between October 2003 and December 2014. Finally, prospective data of 40 patients between December 2014 and October 2015 were used to analyze concordance between score categorization and experts' consensus on surgical procedure. RESULTS: A novel GCTSS included pathological fracture, cortical bone destruction, tumour size, and articular surface involved. The total scores ranged from 1 to 12 points. The strategy for each patient was decided: a total score of 1-4 suggested intralesional curettage alone for excellent post-operative function; 5-9 points indicated intralesional curettage with internal fixation for less surgery-related complications; and 10-12 points indicated prosthesis replacement for long-term local control. The κ-statistic for the predictive validity of total score was 0.611. The κ coefficient of each group represented moderate or substantial agreement, which was acceptable. The intraclass correlation coefficient for inter- and intra-observer reliability of total score was 0.831 and 0.740, respectively. CONCLUSIONS: The novel GCTSS is a comprehensive scoring system with content validity that can aid surgeons in assessing the aggressiveness or severity of giant cell tumour and might become a prognostic tool for surgical decision-making.