[Surgical treatment and prognostic analysis of osteosarcoma in adults older than 40 years].

OBJECTIVE: To determine the prognostic factors of primary osteosarcoma in adults. METHODS: This is a review of 54 patients older than 40 years (24 men and 30 women) who were treated between 1998 and 2011 at the authors' institution. Demographic information and follow-up data were obtained and statistically analyzed. RESULTS: Tumors involved the limbs in 30 patients (55.5%) and axial skeleton in 17 patients (31.5%), and arose from soft tissue in 7 patients (13%). And 6 patients (11.1%) had synchronous metastasis. According to our review, tumors were treated surgically in 52 patients (96.3%). Local recurrence was documented in 14 patients (26.9%). Metastasis after diagnosis appeared in 21 patients (38.9%). In the 52 patients who received the surgical treatment, the 5 year disease-free survival and overall survival rates were 43.7% and 50.4%, respectively. CONCLUSION: Adult patients with primary osteosarcoma had a poor clinical outcome. Inadequate surgical margins, more tumors in the axial location due to high recurrence rates, metastatic disease at presentation, and large tumor volumes were associated with significantly lower survival rates. Aggressive multi-agent treatment regimens might improve survival.

[Evaluation of prognostic factors for synovial sarcoma].

OBJECTIVE: To determine the independent prognostic factors of primary synovial sarcoma. METHODS: The clinical data of 52 patients followed up from 66 patients with synovial sarcoma treated between September 1997 and September 2008 was analyzed retrospectively. There were 28 male and 24 female patients aged from 11 to 71 years old. Three and five-year overall survival (OS), recurrence rate and 9 prognostic factors were analyzed in this study. Univariate and multivariate analysis were performed to determine the prognostic factors of OS. RESULTS: Fifty-two patients were followed up with the follow-up time ranged from 6 to 88 months (median 32 months). The 3-, 5-year overall survival rate and local recurrence rate were 52.8%, 30.3% and 32.7% respectively. Univariate showed tumor size < 5 cm, tumor located at extremities, adequate surgical margin and radical resection combined with radiotherapy had better survival rate (P < 0.05). Multivariate analysis demonstrated that tumor size, primary site and adequate surgical margin were independent prognostic factors for OS. Patients received radical resection combined with radiotherapy have longer median relapse time (25 months) compared with marginal resection combined with radiotherapy (18 months) and single radical resection (12 months). Thirty-five (67%) patients were treated with chemotherapy and seventeen (33%) patients received no chemotherapy for the primary tumor. Treatment with chemotherapy was not associated with an improved OS (P = 0.52). CONCLUSIONS: The independent prognostic factors of synovial sarcoma are tumor size, primary site and adequate surgical margin. Doxorubicin and ifosfamide based chemotherapy was not associated with an improved OS in patients with synovial sarcoma. Radical resection combined with radiotherapy can best control local condition.

Limb Salvage Using Non-hinged Endoprosthesis and Staged Correction of Leg-length Discrepancy for Children with Distal Femoral Malignant Tumors.

OBJECTIVE: Limb salvage in pediatric patients remains a challenge. We describe a staged strategy. The procedure includes: (i) tumor removal and non-hinged static endoprosthesis reconstruction; (ii) leg length discrepancy (LLD) correction by shoe lift or distraction osteogenesis; and (iii) maturity reconstruction by regular endoprosthesis. The aim of the study was to investigate the results of non-hinged static megaprosthesis reconstruction and staged LLD correction in the treatment of malignant tumors in the distal femur in children. METHODS: Non-hinged megaprostheses were implanted in 12 pediatric patients with osteosarcoma in the distal femur. The prosthesis consists of a femoral component with constrained condylar knee (CCK) design, and a tibial component with a small-diameter press-fit stem and derotation fins. A posterior stabilizing polyethylene component is fixed on the tibial component. The cases were prospectively followed up with focus on the growth rate of adjacent uninvolved bone in the salvaged limb, joint stability, knee stability, function outcome, length discrepancy, and surgery-related complications. RESULTS: There were five girls and seven boys included in the study, with an average age at the time of primary surgery of 10.0 years (range, 8-12 years). All the tumors were located in the distal femur. The average follow up was 76.3 months (range, 24-139 months). The Ligament Augmentation and Reconstruction System (LARS) ligament was used in two patients to enhance the soft tissue reattachment and reconstruct medial collateral ligament (MCL). Ten patients were alive at the final follow-up and two had died of lung metastases. Expected LLD was 6.7 cm (range, 3.0-13.2 cm) at initial surgery. At the final follow-up, nine patients reached skeletal maturity and the actual LLD at the femur was 5.3 cm (range, 3.0-10.1 cm), excluding 1 cm correction at initial surgery by endoprosthesis. The proximal tibia physis showed an average of 86.7% (range, 56.5%-100%) growth of the contralateral side. The mean reduction in tibial length was 1.2 cm (range, 0.5-4.7 cm). Six patients received distraction osteogenesis at a mean length of 5.4 cm (range, 3.0-9.1 cm). Range of knee movement was between 85° and 125°, with an average of 102.5°. The Musculoskeletal Tumor Society 93 score of patients alive was 80.6 (range, 60-90). CONCLUSION: Non-hinged static megaprosthesis followed by LLD correction with shoe lift or staged distraction osteogenesis appears to be an alternative option to treat children with malignant bone tumors around the knee.

[Resection and reconstruction of upper thoracic tumor by high transthoracic approach].

OBJECTIVES: To define the role of high transthoracic approach in the treatment of cervicothoracic and high thoracic tumor, and analyze the problem encountered during tumor resection and reconstruction of this technique and oncological results of patients who received this type of surgery. METHODS: Twenty-one patients with cervicothoracic and high thoracic tumor (T(1 - 4)) were treated with high transthoracic approach. This series included metastatic tumor 11 patients, eosinophilic granuloma of bone 2 patients, osteosarcoma 1 patient, Ewing's sarcoma 2 patients, chondrosarcoma 2 patients, giant cell tumor 2 patients, lymphoma 1 patient. High transthoracic approach was applied to these patients for tumor resection and spinal cord decompression. Reconstruction method included artificial vertebrae implantation or bone graft implantation combined with anterior internal fixation. RESULTS: Chest-back pain of all patients relieved significantly after operation. Paraplegia of 3 patients was improved from grade A to grade D according to Frankel grading system, the other 2 patients recovered completely. Pulmonary infection and pulmonary atelectasis occurred in 2 patients; cerebrospinal fluid leakage happened in 1 patient; thoracic aorta rupture happened in 1 patient. The follow-up period was 11 - 58 months, 9 patients died, including 7 patients with metastatic cancer, 1 patient with Ewing's sarcoma, 1 patient with osteosarcoma. CONCLUSIONS: High transthoracic approach is a satisfactory method in dealing with the lesion of cervicothoracic and high thoracic vertebrae, especially with the lesion involving the vertebrae and single vertebral arch. The thoracic canal can be decompressed effectively by this approach.

[Analysis of complications of osteosarcoma around knee treated by resection and replacement of tumor-type prosthesis].

OBJECTIVE: To summarize the effects and complications of osteosarcoma around knee treated by wide resection and replacement by the tumor-type prosthesis. METHODS: Between July 1997 and July 2004, 117 patients with osteosarcoma around the knee had been treated with wide resection and reconstruction with prosthesis. Alcohol-devitalized tumor bone prosthetic composite were used for reconstruction in 13 patients, and allograft prosthetic composite (APC) were used in 25 patients. All patients accepted 2 cycles of chemotherapy before the surgery. RESULTS: The mean follow-up period was 3.5 years (1 - 8 years). Nine patients had failure of union at the graft-host junction. Fracture of the stem of the prosthesis occurred in 5 patients, late infection was found in 19 patients, and aseptic loosening occurred in 3 patients. Bone fracture occurred in 1 patient and prosthesis sinking occurred in 2 patients. CONCLUSIONS: The tumor-type prosthetic reconstruction offers the best knee function after resection of the tumor around the knee, and recurrence rate can be accepted. However, the tumor-type prosthesis needs further improvement because of the high complication rate.

[Surgical treatment of metastatic spinal tumors by anterial approach].

OBJECTIVE: To investigate the efficacy of surgical treatment of the patients with metastatic spinal tumors by anterial decompression and stabilization. METHODS: From December 1997 to December 2003, 93 patients (40 women and 53 men) with metastatic spinal tumors were treated in our department. The locations of the tumor included, thoracic vertebra (53 cases), lumbar vertebra (33 cases), and cervical region (7 cases). The original tumors included lung cancer (21 cases), renal cancer (13 cases), prostate cancer (8 cases), hepatic cancer (5 cases), breast cancer (13 cases), thyroid cancer (5 cases), gastrointestinal tumor (3 cases), and multiple myeloma (8 cases). However, no primary tumor was found in the rest of 17 cases. Among 54 of 93 patients who presented with neurological dysfunction, 16 patients completely paralyzed and others incompletely paralyzed. The follow-up time ranged from 10 to 72 months. RESULTS: Pain was relieved in 87 of 93 patients (93.5%) and neurological function was improved in 47 of the 54 patients. Among 16 completely paralyzed patients, 7 patients experienced a neurological function improvement (from Frankel grade A or B to C or D after decompression). The average amount of blood transfused was 3000 ml. No severe complications were seen in our series. The one-year survival rate was 85% (79 cases). CONCLUSIONS: The integrity of the spinal column structure and neurological function should be considered firstly in the treatment of spinal metastasis. Thorough resection of metastatic tumor and stable internal fixation by anterior approach should be performed when single or two vertebra are involved. In order to alleviate paralysis, promote spinal stability, and improve the quality of life, urgent decompression should be performed on patient with spinal metastasis.

[The surgical palliation of operation combined with vertebroplasty for multiple spinal neoplasm].

OBJECTIVE: To discuss the effect and complication of spinal operation combined with vertebroplasty in treating for multiple spinal neoplasm. METHODS: During the last two years, 20 patients (13 male and 7 female) with multiple spinal neoplasm including metastases, multiple myeloma and lymphoma were treated by operation combined with vertebroplasty, 2 vertebral body segments were involved in 5 cases, 3 to 4 vertebral body segments were involved in 11 cases, more than 5 segments were involved in other 4 cases. Neurological function deficit and severe pain were seen in all the cases. Patients were evaluated by Tomita prognostic scoring system before the operation; The average point was 7.2 (from 3 to 9 points). RESULTS: The pain relief rate was 85% (17/20), and neurological recovery was found in 10 out of 12 patients who had neurological deficit. According to the system of Frankel and neurological function, 1 patient recovered from grade B to grade C after the operation, and there was no change in another patients who was evaluated as grade A before the operation. The main complication of vertebroplasty was leakage of PMMA. Six patients had leakage of PMMA into adjacent structures in this series. CONCLUSIONS: Better results of pain relief and neurological function recovery and living quality can be achieved by surgical palliation of operation combined with vertebroplasty for multiple spinal neoplasm.

[In vitro antitumor immune response induced by fusion of dendritic cells and Ewing's sarcoma cells].

OBJECTIVE: Human Ewing sarcoma A673 cells and human peripheral blood-derived DCs were fused to induce an antitumor activity against human EW. METHODS: EW A673 cells and human peripheral blood-derived DCs were fused with polyethylene glycol (PEG). RESULTS: Mature DCs with highly expressed surface markers (CD80, CD86, CD83 and HLA-DR) were generated in vitro and flow cytometry. It showed that the highest fusion efficiency was 23.01%. T cell proliferation assay indicated that the novel dendritomas in fused DCs/A673 cells were the most potent in activation of autologous T cell proliferation. The IFN-gamma assay showed that The IFN-gamma secretion by CTLs activated by the novel dendritomas increased more than by other stimulators. CTL assay demonstrated that the novel dendritomas induced A673 cell-specific cytotoxic responses to lyse the A673 cells in the context of MHC class I. CONCLUSION: The data indicates that fusion of tumor cells with DCs is an attractive strategy to induce tumor rejection.

[Neoadjuvant chemotherapy for osteosarcoma].

OBJECTIVE: To summarize the experience in neoadjuvant chemotherapy for osteosarcoma. METHODS: Between July 1996 and December 2002 113 patients, 65 males and 48 females, aged 7 approximately 31, with osteosarcoma located in pelvis (n = 2), sacrum (n = 1), proximal femur (n = 6), shaft of femur (n = 4), distal femur (n = 49), proximal tibia (n = 37), shaft of tibia (n = 2), distal tibia (n = 1), fibula (n = 3), scapula (n = 1), clavicle (n = 1), or proximal humerus, (n = 7) without metastasis, 7 of which being at the Ennecking stage of IIA and 106 of which being at the stage of IIB, underwent 2 cycles of chemotherapy with high dose methotrexate (MTX) preoperatively and then operation. If poor response was observed after the first cycle of chemotherapy MTX was abandoned and operation was performed immediately. Twenty-two patients underwent reimplantation of devitalized tumor bone and 80 patients underwent prosthetic replacement. The protocol of cisplatin, ifosfamide, and paclitaxel was adopted after operation. At least 3 cycles of chemotherapy were given postoperatively for all patients. The patients were followed up for 20 approximately 66 months. RESULTS: Sixty patients showed excellent response to the preoperative chemotherapy, 35 showed good response, and 18 showed poor response. Relapse of tumor was found in 12 out of the 22 patients (55%) receiving reimplantation of devitalized tumor bone and in 5 out of the 60 patients (8.3%) receiving prosthetic replacement. The 5-year survival rate of the whole group was 71.93%. The lung metastasis rates were 18.3%, 37%, and 78% in the preoperative excellent response group, good response group, and poor response group respectively. CONCLUSION: The neoadjuvant chemotherapy protocol with the second-line drugs such as ifosfamide and paclitaxel used to the patients responding poorly to MTX is more effective than the older protocol. Local arterial chemotherapy is feasible.

[Surgery for multiple myeloma of the bone].

OBJECTIVE: To investigate the indication, approach and results of the surgical treatment of multiple myeloma. METHODS: The authors reported 29 surgically-treated patients with solitary or multiple myeloma of the bone between January 1997 and January 2002. There are 17 males and 12 females with average age of 59.5 years (range 38 - 76 years). The primary tumour localizations were: vertebral column in 9, rib in1, humerus in 2, proximal femur in 2, femur shaft in 3, pelvis in 6, sacrum in 6. The 29 patients had undergone the following surgical procedures: vertebral tumours were excited through the anterior or posterior approach, combined with a stabilizing procedure in 7 cases. Tumors on thoracic spine were resected using anterior approach. 4 endoprotheses of replacement were performed, indnding two on proximal femur, one on humerus, and one on pelvis. The pathologic fracture was fixated by internal fixation. Neurological impairment was evaluated according to Frankel system. The study evaluated the complications, neurologic function improvement, life quality, and survival after the surgical treatment. RESULTS: The pain was relieved in all cases and the neurological function was improved after the surgery. Local recurrence were found in three cases during the follow-up time. CONCLUSION: The symptom of the patients can be relieved by the surgery. Our experience suggests that surgical interruption on multiple myeloma in some cases may be rewarding.

[Resection and reconstruction for primary pelvic tumors around acetabular].

OBJECTIVE: To discuss the resection of tumors, reconstruction of defects and the postoperative complications. METHODS: Thirty-one patients with tumors around acetabular were treated surgically in People's Hospital between July 1997 and July 2003. The series comprised 19 males and 12 females. Twelve patients were diagnosed with chondrosarcoma, 1 with Ewing sarcoma, 3 with osteosarcoma, 1 with lymphoma, 1 with carcinosarcoma, 1 with malignant fibrohistiocytoma (MFH), 2 with myeloma, 9 with giant cell tumor (GCT), 1 with aneurysmal bone cyst. Among 31 patients with peri-acetabular tumors, 8 were reconstructed with hemi-pelvic prosthesis, 7 with saddle prosthesis, 6 with cauterized tumor bone and total hip arthroplasty, 10 with total hip replacement after curettage of lesion and cemented. RESULTS: Among 21 patients who underwent tumor resection and reconstruction in region II, 6 had local relapse. Two of 3 patients with osteosarcoma were dead. Five of 12 patients with chondrosarcoma were free of disease. Twenty-one patients with acetabular reconstruction after resection of lesions in region II could sit and stand normally and walked with a cane, several of which even had normal gait. CONCLUSION: Allograft or pelvic prosthesis can be used to reconstruct the acetabulum after resection of tumors. We must pay more attention on the following points in the surgical treatment of periacetabular tumors: (1) Extensively resect tumors as far as possible; (2) Be acquainted with advantages and disadvantages of different reconstructive methods of acetabulum to prevent the complications; (3) The reconstructed acetabulum is unstable, so the patients must stand with a cane to protect the reconstructed hip joint; (4) Prevent wound necrosis and infection; (5) Surgical treatment of pelvic tumors would easily result in poor wound healing especially in the patients receiving chemotherapy or radiotherapy because of extensive soft tissue stripping. The destroyed soft tissue caused by chemotherapy or radiotherapy may increase the great tissue tension after implantation of allograft. And the factors of poor blood supply and hematoma in the wound theoretically increase the chance of infection.

Sorafenib induces growth inhibition and apoptosis in human synovial sarcoma cells via inhibiting the RAF/MEK/ERK signaling pathway.

Synovial sarcoma is a soft tissue sarcoma with poor prognosis and lack of response to conventional cytotoxic chemotherapy. The regulatory mechanisms for the rapid proliferation of synovial sarcoma cells and the particular aggressiveness of this sarcoma remain poorly understood. Mitogen-activated protein kinase (MAPK) cascades have been shown to play important roles in synovial sarcoma survival. Sorafenib (Nexavar, BAY 43-9006), a potent recombinant activated factor (RAF) inhibitor, inhibits the MAPK signaling pathway both in vitro and in vivo. In this study, we examined the inhibitory proliferation effects of sorafenib in synovial sarcoma growth and evaluated whether sorafenib modulates MAPK and tumor apoptosis cascades in human synovial sarcoma cell lines SW982 and HS-SY-II. Our results indicated that sorafenib effectively inhibited cellular proliferation and induces apoptosis of these two cells. Sorafenib inhibited the phosphorylation of MEK and ERK, downregulated cyclin D1 and Rb levels, caused G(1) arrest and S phase decrease, and induced apoptosis as confirmed by flow cytometry and the TUNEL assay. Furthermore, Bcl-xl and Mcl-1 levels significantly decreased, whereas expression levels of the proteins bcl-2 and bax were unchanged in response to sorafenib treatment in SW982 and HS-SY-II cells. In conclusion, our findings demonstrate that sorafenib is effective for growth inhibition of synovial sarcoma cell lines in vitro and suggest that sorafenib may be a new therapeutic option for patients with synovial sarcoma.