Inactivated Bone Replantation with Preservation of the Epiphysis in Children with Osteosarcoma:Clinical Report of Two Cases

Objective: To evaluate the value of inactivated bone replantation with preservation of the epiphysis following the effective chemotherapy in avoiding postoperative discrepancy of the affected limb in children with osteosarcoma. Methods: Two children (aged 5 and 10 years, 1 male and 1 female) with osteosarcoma underwent inactivated bone replantation with preserving epiphysis following chemotherapy (MMIA protocol, including high-dose methotrexate, adriamycin and ifosfamide). After two cycles of preop-erative chemotherapy, pain vanished, the local mass shrank and there was no pain on pressing the affected parts. Sera AKP and LDH were reduced to normal levels; marked shrinkage and sclerotic changes and good margin of lesions were seen on plain radiographs and MR images. Two courses of the same protocol as preoperative chemotherapy were administered postoperatively. Results: Postoperative histological examination of the specimens demonstrated absence of vital tumor cells. Incisions healed well and no complications occurred. The replanted inactivated bone healed with host at 6 months after operation. In the two patients, no evidence was seen of metastasis and recurrence and discrepancy of the affected limbs in postoperative 36 and 48 months. Functions of the affected limbs were satisfactory. Conclusion: Inactivated bone replantation with preserving epiphysis was a viable option for osteosarcoma in children. The long-term outcomes remain to be further proven.

Expression of Survivin Gene and Its Relationship with Clinical Multidrug Resistance in Osteosarcoma

Objective: To study the expression of survivin and its relationship with clinical multidrug resistance in osteosarcoma. Methods: By using immunohistochemistry (S-P) method, the expression of Survivin in osteosarcoma, osteochondroma and normal osseous tissue, and the expression of P-glycoprotein in osteosarcoma was detected. Results: Survivin positive expression rate was 65.71% in osteosarcoma, but no expression of Survivin was detectable in osteochondroma and normal osseous tissue. The positive expression rate of Survivin was significantly associated with Enneking clinical stages and histological typing (WHO), but no relationship was found among Survivin expression and age, sex and tumor location. The positive expression rate of P-glycoprotein was 45.71%. There was a significant correlation between Survivin and p-glycoprotein. Conclusion: Survivin overexpression was significantly associated with clinical multidrug resistance in osteosarcoma. It could be a potential target for treatment of osteosarcoma.

Influence of neoadjuvant chemotherapy on proliferation, apoptosis and multi-drug resistance in osteosarcoma cells

Objective: To study the influence of neoadjuvant chemotherapy on the expression of cyclin D1, Bcl-2, PCNA and P- gp in osteosarcoma cells and the relationship between the expression and tumor cell necrosis rate (TCNR) after chemotherapy. Methods: By using immunohistochemistry, the expression of cyclin D1, Bcl-2, PCNA and P-gp was detected in 23 cases of osteosarcoma and TCNR were calculated. Results: The pre-chemotherapy positive expression rate of cyclin D1, Bcl-2, PCNA and P-gp was 73.9%, 69.6%, 91.3% and 21.7%, respectively, and that post-chemotherapy positive expression rate was 52.1%, 34.8%, 43.5% and 56.5%, respectively. The positive expression rate of Bcl-2 and PCNA after chemotherapy was much lower than that before chemotherapy (P=0.039, 0.034). After chemotherapy, the expression rate of P-gp was higher (P=0.021) and the expression of cyclin D1 had no statistically significant difference (P=0.180) comparing with that before chemotherapy. No correla- tion existed between the expression of cyclin D1, Bcl-2, PCNA, P-gp and TCNR before chemotherapy (P=0.155, 0.371, 1.000 and 0.640). There was a negative correlation between the expression of Bcl-2, PCNA, P-gp and TCNR (P=0.009, 0.012 and 0.015), but no relationship existed between the cyclin D1 and TCNR (P=0.100) after chemotherapy. Conclusion: Chemotherapy could inhibit proliferation and induce apoptosis of osteosarcoma cells. At the same time, due to the overexpression of the P-gp, the drug resistance of the osteosarcoma cells was increased. The detection of cyclin D1, Bcl-2, PCNA and P-gp in osteosarcoma samples before chemotherapy might not be used to predict the curative effect of the chemotherapy.

A Case Report of Multiple Aneurysmal Bone Cysts

A 30-year old male patient, admitted in our hospital for a fracture of the upper end of the left humerus in February, 2006, received treatment with curettage of the lesion in combination with an autologous bone graft from the right ilium plus internal fixation. A post-operative pathological examination indicated that there was a simple bone cyst in the area of the fracture, with a satisfactory postoperative recovery.

An Overview of CyberKnife Radiosurgery

Stereotactic radiosurgery is a non-invasive procedure that utilizes precisely targeted radiation as an ablative surgical tool. Conventional radiosurgery devices, such as the Gamma Knife, rely upon skeletally attached Stereotactic frames to immobilize the patient and precisely determine the 3D spatial position of a tumor. A relatively new instrument, the CyberKnife (Accuray, Inc., Sunnyvale, CA), makes it possible to administer radiosurgery without a frame. The CyberKnife localizes clinical targets using a very accurate image-to-image correlation algorithm, and precisely cross-fires high-energy radiation from a lightweight linear accelerator by means of a highly manipulable robotic arm. CyberKnife radiosurgery is an effective alternative to conventional surgery or radiation therapy for a range of tumors and some non-neoplastic disorders. This report will describe CyberKnife technology and oncologic applications in neurosurgery and throughout the body.

Expression and clinical significance of PTEN protein in osteosarcoma

Objective： To investigate the expression and significance of cancer inhibitory gene PTEN protein in osteosar-coma. To analyze the level of its expression in different histological classification of osteosarcoma. To determine the possibility of taking PTEN protein as a marker gene for diagnosing osteosarcoma. To observe the clinical value of PTEN expression levels as a reference index for osteosarcoma classification. Methods： 43 specimens collected from osteosarcoma excision were studied. 30 specimens collected during the same period from benign lesion of bone （osteochondroma） operation were taken as the control group. Immunohistochemistry staining （ElivisonTM two steps method） was used to detect the expression of PTEN protein in 43 cases of osteosarcoma. SPSS 10.0 was used in statistical analysis. Results： Immunohistochemistry staining showed that the positive reaction of PTEN protein was all oriented to cytoplasm, which were brown or yellowish- brown granules. By way of X^2 test, the significant difference of the positive expressions of PTEN protein between bone benign lesion and osteosarcoma （X^2 = 7.976, P 〈 0.01） was observed. Osteosarcoma with different degrees of histodifferentiation showed different level expression of PTEN protein. There was significant difference between well-differentiated osteosarcoma （grades Ⅰ-Ⅱ） and poorly-differentiated osteosarcoma （grade Ⅲ） statistically （P 〈 0.01）. The level of expression of PTEN was negatively correlated to the histological grade of osteosarcoma. There was great significance statistically （rs=-0.4922, P 〈 0.01）. Conclusion： PTEN protein may be used as candidate gene of cancer inhibitory gene： PTEN protein is a cancer suppressor gene protein which has expression in bone tumors. It might not only be used in the study of pulmonary carcinoma and neurogliocytoma, but also in the study of bone tumor; the expression of PTEN is related to benignancy or malignancy of bone tumor and their degree of differentiation. The expression of PTEN is positively correlated with degree of differentiation.

ADSORPTION OF ^(153)Sm-EDTMP ON HYDROXYAPATITE

Adsorption of a promising bone tumor therapeutic agent 153Sm-EDTMP (ethylene diamine tetramethylene phosphonic acid) and effects of several coexisting substances on adsorption and desorption were investigated using HA (hydroxyapatite) as an in vitro model. The adsorption is quantitative up to total deposition of 40 μmol/g HA, while nonquantitative when the complex concentration is above 40μmol/g HA in the medium of pH=7.0±0.2. The uptake increases significantly with the Ca ions added. Desorption of the adsorped complexes is in the sequence of EDTMP DTPA > EDTA. Two modes of adsorption of 153Sm-EDTMP on HA are suggested, the first one ( 40μmol/g HA) quantitatively covers the available surface and the second, by which, is less efficient, additional complexes are adsorped. Non-qualltitative adsorption is attributed to Coulomb repulsion while the complex concentration ranging from 40 to 80 μmol/g HA.

Extracranial metastasis of anaplastic oligoastrocytoma

Extracranial metastasis(ECM) of glioma is a rare condition that occurs in the internal nervous axis. A 23-year-old woman presented with anaplastic oligoastrocytoma(WHO III) in a left temporal tumor. The patient received chemoradiotherapy after surgery in our center. Three years after treatment, the patient experienced multiple ECMs in the right lung, left iliac bone, and multiple swollen subcutaneous nodules including the right clavicle, back of the neck, left forearm, right upper arm, and right clavicle. The patient died of cerebral herniation at the age of 27 due to recurrent intracranial glioma. Treatment of ECM of glioma remains very challenging, and further investigations are needed.

Neoadjuvant chemotherapy for osteosarcoma of the extremity: Outcome of the Chinese 1st protocol in a single institute

Objective： The aim of this study was to determine stand protocol for patients with extremity osteosarcoma by case following up after neoadjuvant chemotherapy and limb salvage operation. Methods： Between January 2000 and January 2007, 121 patients with extremity osteosarcoma were eligible for this analysis. After being graded according to Enneking classification, all patients were preoperative chemotherapy （methotrexate, cisplatin, doxorubicin, and ifosfamide. Some patients with liB tumors received extra interventional embolism）. And postoperatively, the same protocols were employed, but poor responders （tumor necrosis 〈 95%） received more treatment cycles than good responders and took some new medicine in place of the former one. Most of patients underwent limb salvage operation （99/121）, and the Musculoskeletal Tumor Society Score （MSTS） was used to evaluate the recovery of their limb functions. Results： The followed up last for average 37.3 months （range： 16-101 months）. Most patients （76/121） survived, and the overall survival （OS） was 62.8%. Forty-seven of the 121 patients underwent osteoarticular allografts, among which 12 cases of disunion between the host bone and graft bone, 4 cases of allograft absorption and 3 local recurrences appeared. The mean MSTS score was 22.6 ± 4.13, with an excellent limb function in 17 patients, good in 19 patients, fair in 6 patients and poor in 7 patients. The overall excellent and good function outcome was obtained in 76.6% of the patients. Fifty-two of 121 patients underwent custom-made or modular tumor endoprosthesis replacememt, among which 1 case of aseptic loosening, 1 case of peri-prosthesis infection and 4 local recurrences appeared. The mean MSTS was 24.32 ＋ 3.85, with an excellent limb function in 28 patients, good in 16 patients, fair in 5 patients and poor in 3 patients. The overall excellent and good function outcome was obtained in 84.6% of the patients. Conclusion： Neoadjuvant chemotherapy and limb salvage surgery are effective methods to treat osteosarcoma at present, although some patients still dying from postoperative metastases. Therefore, early diagnosis individualized treatment and exploring for new and effective therapeutic strategy should be the key to an ideal treatment for osteosarcoma.

Limb salvage surgery for malignant bone tumors of the extremities in children and adolescents

Objective： The aim of the study was to analyze the clinical features of limb salvage surgery with epiphyseal preservation in children and adolescents, and to evaluate the recurrence rate, metastasis, complications, and the joint functional results after tumor resection. Methods： Between December 1995 and January 2003, 33 cases of preserving epiphysis procedure had been done. In this group, the tumor located in distal femur in 24 cases and in proximal tibia in 9 cases. There were 23 osteosarcomas, 6 Ewing＇s sarcomas, 2 chondrosarcomas, and 2 aggressive osteoblastomas. The patients received 2-4 cycles of preoperative adjuvant chemotherapy, and another 6 cycles after surgery. The modified protocol T10 was taken. Radiography and MRI were used to determine the margins of the tumors preoperatively and histological examination was used to corroborate the evidence intraoperatively. The tumors were staged clinically. Among them, there were 2 cases in ⅠA, 2 cases in ⅠB, 17 cases in ⅡA, and 12 cases in liB. According to the MRI analysis, the metaphyseal tumors in children were classified into 3 types. Type Ⅰ, with the tumor close to but not contacting epiphyseal plate, and the distance between the two over 2 cm, was taken as absolute indication for the technique. Type Ⅱ, with the tumor near or contacting epiphysis plate, and the distance between the two less than 1 cm, was taken as relative indication for the surgery. For type Ⅲ, the tumor contacted the epiphyseal plate partially, and was over 2 cm beyond the joint. In the cohort, 18 cases were categorized as type Ⅰ, 13 as type Ⅱ, and 2 as type Ⅲ. The size of the residual epiphyseal bone segment differed after different excision protocols which were taken according to the clinical classifications. Bone defects after tumor resections were repaired with massive intercalary allograft bone, followed by internal fixation by intramedullary nails and cancellous screws. Results： Among the 33 cases, 3 cases were lost to follow up. 29 cases had complete clinical data. Postoperative follow-up was 12-72 months. Recurrences were seen in 3 cases, with one local recurrence in type Ⅲ cases one year post tumor resection, other 2 recurrences around the femoral vessels in type Ⅱ cases 15 months and 30 months after the tumor resection respectively. The recurrence rate accounted for 10.34%. Amputation was performed for the cases with recurrences. But pulmonary metastasis developed and the patients died. In this cohort, 9 cases died. Five-year survival rate constituted 57.94% demonstrated by Kaplan-Meier survival analysis. The median survival time for male patients was 64.36 months, and that for female patients was 56.00 months （P = 0.0403）. The sites, stages and types were not associated with the survival time. Four cases reported 5 complications （17.24%）. The complications included fracture of the allograft, limb length discrepancy, nerve injury, breakage of nails, and loosening of the screws. No patient reported skin necrosis, hematoma, infection, rejection to the allograft, and nonunion at the end of the follow-up. According to the functional evaluation criteria after surgical treatment of malignant tumors of the extremities introduced by Enneking, excellent functional results were reported in 11 cases, good in 13 cases, fair in 3 cases, and poor in 2 cases. The excellent or good result rate was 83%. The excision interface involved partial epiphysis in 4 cases, involved the epiphyseal plate in 8 cases. Intact epiphysis was preserved in 17 cases. Five cases with poor postoperative functional results were in types II and III. Average time of bone union was 2.5 months for epiphyseal end and 3.8 months for diaphyseal end. According to the International Society of Limb Salvage （ISOLS） radiological implants evaluation system, excellent reconstruction was observed in 23 cases, good reconstruction in 4 cases, fair reconstruction in 1 case, and poor reconstruction in 1 case. All patients in the group had satisfactory joint stability. No patient reported joint dislocation, valgus or varus deformity, and osteoarthritis. The average limb length discrepancy was 3.2 cm, ranging 2-6 cm. Conclusion： The limb salvage surgery with preservation of epiphysis for malignant bone tumors in children and adolescents guarantees the patient＇s satisfactory postoperative limb functional results. Preoperative effective adjuvant chemotherapy and prevention of postoperative complications deserve great attention.

Development of multiple myeloma in a patient with gastrointestinal stromal tumor treated with imatinib mesylate:a case report

Gastrointestinal stromal tumors (GISTs) are rare tumors, which represent approximately 1% of the neoplasms of the gastrointestinal tract. These tumors rarely give extra-abdominal metastases. However, their clinical outcome is potentially adverse. In some rare cases, co- existance of GISTs with other malignancies has been reported. Here we present a case of a 74-year old male with GIST, which was managed by surgical resection. Fourteen months later, the patient presented with liver metastases and imatinib mesylated was administered. During treatment, the patient reported skeletal pain and plane X-rays revealed osteolytic bone lesions. Further investigation revealed the presence of multiple myeloma. To the best of our knowledge, this is the first report of the co-existence of multiple myeloma (MM) with GIST.

Therapy of Multiple Myeloma

Summary Multiple Myeloma(MM)is characterised by the accumulation of malignant plasma cells in the bone marrow producing a monoclonal immunoglobulin.The standard conventional therapy is the combination of melphalan and prednisone resulting in a response rate of 40%-60%and in a median survival time of approximately 3 years.In order to improve the therapeutic efficacy various combination regimens have been tested.Most randomized trials have frailed to show a significant improvement in survival time when combination chemotherapy is used instead of melphalan with or without prednisone.The benefit of maintenance therapy with interferon-alpha has been demonstrated.The toxicity of interferon-alpha,which may reduce the quality of life,should be considered.Recently,myeloma-treatment has been modified.High-dose chemotherapy accompanied by hematopoietic stem-cell support via autologous transplant is recommended up to the age of 65-70 years.First results from a French study comparing single versus double autologous transplantation have shown a benefit in terms of event-free survival for the sequential approach.Vaccinations as an adoptive immuntherapy to treat minimal residual disease are under way.The mortality rale of allogeneic transplantation of hematopoietic stem cells has been reduced in the last 5 years.The use of reduced conditioning regimens or the partial depletion of T cells in peripheral blood stem cell transplants in an effort to decrease transplant related mortality are promising approaches.Thalid-omide and its derivates are a new class of agents with independent anti-tumour activity in MM.Encouraging results with this antian-giogenic therapy in phase II trials have been reported.Supportive therapies,such as the treatment of anaemia with erythropoietin,the management of renal failure and the use of bisphosphonates,improve the life quality of MM patients.

Diaphyseal Chondroblastoma in the Tibia: One Case Report and Literatures Review

Introduction Chondroblastoma is a rare benign cartilaginous neoplasm that accounts for approximately 1% of all bone tumors and characteristically arises in the epiphysis of a long bone, particularly the humerus, femur and tibia. Chondroblastoma can affect people of all ages. However, it is most common in children and young adults between the age of 10 and 20 years. Occasionally it can be followed by a more aggressive course invading the joint spaces, adjacent bones and rarely resuiting in metastases. It is defined as a lytic bone lesion with a predilection for the epiphyseal region of long bones in skeletally immature individuals, although 50% of the tumors also involve the metaphysis. However, purely metaphyseal and diaphyseal tumors are exceedingly rare. In fact, the only diaphyseal chondroblastoma we found in the literature was located in a metacarpal bone and the distal femor. We describe a Chondroblastoma arising from the diaphysis of the tibia, which, to the best of our knowledge, is the first diaphyseal chondroblastoma of the tibia reported in the world literature.

The experiment study on LMWH inhibiting the expression of Livin and inducing the apoptosis of osteosarcoma cells

Objective: To investigate the inhibitory effects of LMWH suppressing the expression of Livin and inducing the apoptosis of the osteosarcoma cells. Methods: Osteosarcoma cells line MG-63 was cultured in vitro. MTT assay and flow cytometry were used to study the effect of LMWH with different concentration suppressed the prolifetation and induced apop- tosis in osteosarcoma cells line MG-63. The expression of Livin of osteosarcoma cells line MG-63 was analysed by the im- munohistochemistrical method and PT-PCR. Results: Low molecular weight heparin could inhibit the growth of osteosarcoma cell line MG-63. With the LMWH's increasing, the apoptosis rate was increased significantly. Immunohistochemistrical method and PT-PCR showed that the expression of Livin of osteosarcoma cells line MG-63 declined obviously than that before medi- cation. Conclusion: LMWH has very strong anti-tumor effect in vitro. The possible mechanisms of LMWH anti-tumor effect are associate with the effect of suppressing the expression of Livin and inducing cell apoptosis.

REPEATED RECURRENCE OF OSTEOSARCOMA TREATED BY RESECTIONS AND CHEMOTHERAPY

This paper presents 5 patients with repeated recurrence of osteosarcoma (RROS). The primary focus of 3 patients were in the distal portion of femur, and 2 patients were in the proximal Portion of tibia. Three patients, whose chest X ray film were negative, were treated by amputation and chemotherapy. Two patients had isolated metastatic focus l. 5 cm in diameter in lung, were treated by amputation after 1 week of chemotherapy and then treated by lobectomy after 2 weeks of chemotherapy. After operation, the chemotherapy was carried out for 3 courses of treatment. The roentgenogram of chest and affected limb were taken once every two months. There were metastatic focuses found in the lung of 1 patient and in the distal portion of femur of 2 patients. One patient was operated on for 4 times. UP to now, 3 patients have been living for 5 yeara and 2 patients for 6 years after operation.

Progress in Drug Therapy for Multiple Myeloma

Multiple myeloma remains incurable with conventional treatments.However,new active drugs,including the immunomodulatory agents,thalidomide and lenalidomide, and the proteasome inhibitors bortezomib and NPI-0052,and other targeted therapies,have shown promising anti-myeloma activity.These agents represent a new generation of treatments for multiple myeloma that affect both specific intracellular signaling pathways and the tumor microenvironment.This review therefore focuses on the extensive clinical data available from studies of these drugs in the treatment of newly diagnosed,refractory and relapsed multiple myeloma.

GAS7 expression and its significance in human osteosarcoma

Objective： To detect the expression of GAS7 in osteosarcoma and discuss its significance. Methods： Immunohistochemistry SABC method was applied to detect GAS7 expression in specimens of 54 osteosarcoma and 15 osteochondroma cases. Results： The positive expression rate of GAS7 was 74.7% （40/54） in the group of osteosarcoma and 0% （0/15） in the group of osteochondroma. There was a significant difference in the comparison of GAS expression in these two groups （P 〈 0.05）. GAS7 was higher expressed in the samples which complicated with relapse or pulmonary metastasis than the control group （P 〈 0.05）. There was no significant association between GAS7 expression and the size of tumor, the gender or the age of the patients （P 〉 0.05）. Conclusion： The hyper-expression ot GAST may play an important role in the initiation and development of human osteosarcoma.

Operative treatment via anterior approaches for cervicothoracic vertebrae tumors:surgical techniques and primary outcome

Objective： To sum up 7 patients with cervicothoracic vertebrae tumors （Cr to T3） from March 1999 and May 2002, who underwent operative treatment via anterior approaches. Methods ：The anterior approaches included low anterior cervical approach and high transthoracic approach. In 5 cases of segments of T1 and above involved, the low anterior cervical approaches were adopted, otherwise the high transthoracic approaches were used（2 cases）. Excision of tumor was carried out according to demands of the Weinstein-Boriani-Biagini （WBB） staging system. Spine stability was reconstructed by bone autografting and instrumentation. There were 4 cases of primary tumor and 3 of metastases. Their mean age was 45. 1 years （23 to 66）. The mean follow-up was 18.9 months （3 to 45）. Results were evaluated by occurrence of complications, improvement of symptoms, local recurrence and mortality. Results： All patients stood surgery well. No significant complications occurred during and after operation. Local pain was significantly alleviated and neurological deficit was improved at least one Frankel grade. Three patients died. Local tumor control was obtained in 6 patients （85.7 % ） until the end of follow-up. Conclusion.-Our experience showed that via low anterior cervical approach and high transthoracic approach, the cervicothoracic vertebrae tumor could be excised safely and adequately. Moreover, excision of tumor according to the WBB surgical staging system and reconstruction of spine stability have made great contribution to local tumor control and the neurological function improvement.

The value of radionuclide bone imaging on monitoring chemotherapeutic effects of multiple myeloma

Objective： To investigate the value of radionuclide whole-body bone imaging on monitoring chemotherapeutic ~ffects for multiple myeloma （MM）. Methods： Sixty patients were included. Twenty nine cases received CTD （thalidomide 100-200 rag/d; cyclophosphamide 200-300 mg/m2od, 1-4 days, every 4 weeks; and dexamethasone 20-40 rag/d, 1-4 days, every 4 weeks）; Thirty cases received VAD （vincristine 0.4 mg/d, 1-4 days, every 4 weeks; adriamycin 10 mg/d, 1-4 days, every 4 weeks; dexamethasone 40 rag/d, 1-4 days, every 4 weeks）. Radionuclide bone imagings were performed in all patients before chemotherapy, six months, twelve months and eighteen months after chemotherapy. The correlation of chemothera- peutic effects between CTD and VAD were analyzed. Results： One hundred and seventy nine bone lesions were visualized by bone scintigraphy before CTD treatment. Eighteen months after CTD chemotherapy, it was observed by bone scintigraphy that 39/179 （21.78%） lesions disappeared, 112/179 （62.57%） improved, and 281179 （15.64%） had no change. One hundred and ninety one bone lesions were showed by bone imaging before VAD treatment, 361191 （18.84%） lesions disappeared, eighteen months after chemotherapy, 103/191 （53.92%） improved, and 52/191 （27.22%） had no change. The significant dif- ference was observed in locations of MM induced bone lesions treated with CTD （H = 8.23, P 〈 0.05） and VAD （H = 11.18, P 〈 0.05）. A significant chemotherapeutic sensitivity in detecting MM induced lesions in ribs was found compared with other bone lesions. The chemotherapeutic effect of CTD was statistically significant than that of VAD （U = 2.17, P 〈 0.05）. Conclusion： Radionuclide whole-body bone imaging has great value in monitoring chemotherapeutic effects for MM.