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PubMed1999

Osteosarcoma of the pelvis.

Over a 25-year period we have treated 36 patients with osteosarcoma of the pelvis. Of the tumours, 24 (67%) were primary osteosarcomas and 12 (33%) arose either after irradiation or in association with Paget's disease. Six patients had a hindquarter amputation and 12 were treated by a limb-salvage procedure with intrapelvic excision. The five-year survival rate of all the patients with pelvic osteosarcoma was 18%, while for 17 treated by chemotherapy and surgery it was 41%. The prognosis for patients presenting with metastases or with secondary osteosarcoma was appalling and none survived after 29 months. No patient over the age of 50 years when seen initially survived for a year. Youth and a good response to chemotherapy along with complete surgical excision offer the best chance of cure.

Adolescent↗
PubMed2002

Pirarubicin-based versus doxorubicin-based osteosarcoma chemotherapy.

OBJECTIVE: To conduct a retrospective evaluation of tetrahydropyranyladriamycin (PIR)-based combination chemotherapy for osteosarcomas in comparison with doxorubicin (DOX)-based regimens to determine differences in response and toxicities between DOX- and PIR-containing regimens. METHODS: Toxicities and response rates of the 2 anthracyclines given as combination chemotherapy were assessed in patients with osteosarcoma, with 19 patients receiving PIR-based and 11 receiving DOX-based regimens. RESULTS: The survival of osteosarcoma patients treated with PIR was significantly better than that with DOX (p = 0.023) based on 2-year follow-up. Adverse effects such as mucositis and diarrhea were also less pronounced in the PIR cohort. CONCLUSIONS: PIR-based combination chemotherapy might be a useful and safe chemotherapeutic strategy for osteosarcomas compared with DOX regimens. Further assessment is necessary to confirm the safety and efficacy of this treatment.

Adolescent↗
PubMed2006

Giant cell osteosarcoma in the calvarium of a cat.

Feline primary osteosarcomas involving the skull are extremely rare. When they occur, orbit, mandible, and maxilla are the most common sites. Microscopically, scattered multinucleated giant cells (MGCs) are not an uncommon occurrence in osteosarcoma (OSC), but they are generally in low number. Only in a rare variant, the giant cell-rich OSC, are MGCs the prevalent cell type. Although osteoclast and osteoblast origin have been postulated in human and veterinary literature, the origin of MGCs in osteosarcomas is poorly understood. This report describes a giant cell-rich OSC in the calvarium of a 13-year-old spayed female shorthair cat. The animal exhibited a range of neurologic signs, including left circling, compulsive gait, lack of proprioception, and bilateral absence of menace reaction, with indication of left forebrain involvement. Gross lesions were characterized by a multilobate, spherical mass located in the left calvarium, compressing the left forebrain. Histologically, the tumor was characterized by scattered nests of MGCs separated by small bundles of pleomorphic, fusate to polygonal cells. Between spindle cells, osteoid was very sparse and arranged in thin strands. Immunohistochemical stains for vimentin were positive, with no detectable cellular staining for cytokeratin, S-100 protein, or Class II major histocompatibility complex. Ultrastructurally, MGCs contained profiles of rough endoplasmic reticulum; no lysosomes were observed. The origin of MGCs in osteosarcoma remains obscure, and our results confirm their ambiguous identity.

Animals↗
PubMed1991

Is there a link between fluoridated water and osteosarcoma?

To test the hypothesis that fluoride is a risk factor for osteosarcoma, a case control study compared the complete residential fluoride histories of osteosarcoma patients with matched hospital-based controls. Fluoridation was not found to be a risk factor for osteosarcoma in the study population. The trend in the data from this small sample study suggests the hypothesis that a protective effect may exist against the formation of osteosarcoma for individuals consuming fluoridated water.

Adolescent↗
PubMed2006

Comparative analysis between osteosarcoma and Ewing's sarcoma: evaluation of the time from onset of signs and symptoms until diagnosis.

OBJECTIVE: The purposes of this study were to describe the early signs and symptoms of osteosarcoma and Ewing's sarcoma, identify symptoms that could be used to help differentiate the two types of tumors, and determine the time elapsed between the onset of signs and symptoms and the definitive diagnosis in our service, providing information and imputus for earlier diagnosis of these tumors. METHODS: A retrospective analysis of the medical dossiers of 365 patients under 30 years of age diagnosed with osteosarcoma or Ewing's sarcoma was performed, and the aspects of the clinical diagnosis were statistically analyzed and compared. RESULTS: The time between the onset of signs and the symptoms was 5.25 months for osteosarcoma and 8.1 months for Ewing's sarcoma, and the most frequent (89.5%) early symptom of osteosarcoma and Ewing's sarcoma was local pain. Symptoms that might aid diagnosis included early local volume increase and the presence of fever. CONCLUSION: The time until diagnosis of both neoplasias was higher than that reported for North America and Europe. Education of the lay public and medical professionals regarding suspicious early signs and symptoms might shorten the delay of diagnosis.

Adolescent↗
PubMed1998

Relation between histological intensity of transforming growth factor-beta isoforms in human osteosarcoma and the rate of lung metastasis.

Even though adjuvant chemotherapy has improved the 5-year survival rate of osteosarcoma patients, a significant percentage of patients eventually die from lung metastasis. Since transforming growth faCtor-beta (TGF-beta) has been demonstrated to be related to the tumor progression, we investigated the clinical implications of the presence of TGF-beta isoforms in 16 human osteosarcoma tissue. There were 10 males and 6 females with a mean age of 20.8 years of age (range, 8 to 57 years). Biopsied specimen before chemotherapy was fixed in 10% formalin, demineralized and followed by paraffin embedding. The locations of tumor included femur (10), tibia (3), humerus (1), fibula (1), and ilium (1). Histologic subtypes included osteoblastic (11), chondroblastic (2), and fibroblastic (3). All patients were followed for a minimum of 1 year (range 12 to 44 months) or to the development of lung metastasis. Five patients (31.3%) developed subsequent lung metastasis during the follow up. We used immunohistochemistry technique to investigate the presence of the TGF-beta isoforms in osteosarcoma tissue and its relationship to the subsequent pulmonary metastasis. The results showed the presence of one or more TGF-beta isoforms in tumor cells in osteosarcoma tissues (13 of 16, 81.3%) in all of the subtypes. However, minimal presence of TGF-beta isoforms was shown in the tumor bone matrix. The expression of TGF-beta1 or TGF-beta3 isoforms was associated with a higher rate of subsequent lung metastasis (p < 0.05, chi-square test). Further research is warranted to determine the utility of routine TGF-beta analysis in the clinical practice.

Adolescent↗
PubMed2006

Osteosarcoma in a patient with neurofibromatosis type 1: a case report and review of the literature.

Neurofibromatosis type 1 (NF1) or von Recklinghausen's disease is a genetic disease generally characterized by café-au-lait spots and neurofibromas. Malignant tumors of the nervous system, such as malignant schwannomas, gliomas, or astrocytomas, have been well known to coexist with neurofibromatosis. However, occurrence of malignant tumors unrelated to the nervous system is rare. We report an unusual case of a 29-year-old NF1 female suffering from malignant peripheral nerve sheath tumor (MPNST) that eventually developed osteosarcoma in the proximal femur. Osteosarcoma is the most common high-grade malignant bone tumor in which the neoplastic cells produce osteoid. At 23 and 24 years old, she underwent excision of MPNST in the left posterior thigh. No osteosarcomatous portion was identified in these specimens. The patient underwent postoperative chemotherapy. At 29, left proximal thigh pain and swelling appeared. Computed tomography demonstrated cortical bone destruction in the left proximal femur where MPNST occurred. Magnetic resonance imaging revealed extraskeletal growth of the tumor. Bone scintigraphy demonstrated increased uptake in the left proximal femur. Hip disarticulation was performed. The removed tumor was composed of highly anaplastic cells. Lace-like irregular osteoid formation was observed among the tumor cells. MPNST component was totally absent. The tumor was diagnosed as osteoblastic type osteosarcoma. Two months after disarticulation the patient died of bilateral pulmonary metastasis. The correlation between the histogenesis of osteosarcoma and the genetic abnormality in NF1 patients has not been elucidated, but the finding of osteosarcomatous transformation in this case suggests the divergent cellular differentiation to mesenchymal malignant tumors of neuroectodermal tissue in NF1 patients.

Adult↗
PubMedDate not supplied

Cyclooxygenase-2 expression in canine appendicular osteosarcomas.

Osteosarcoma is the most common primary bone tumor in dogs and it has a high mortality rate from distant metastatic disease. Targeted adjuvant therapies are needed to prolong currently achievable survival times. The role of cyclooxygenase-2 (COX-2) in carcinogenesis has been attributed to the production of prostaglandins and involvement in apoptosis, immune surveillance, and angiogenesis. COX-2 is up-regulated in a number of different human and animal epithelial tumors, but data about its function in mesenchymal tumors is lacking. The purpose of this study was to evaluate COX-2 expression in canine appendicular osteosarcomas and to identify if a relationship exists between the intensity of COX-2 expression and clinicopathologic outcome. Of 44 osteosarcomas analyzed, 34 (77.3%) were positive for COX-2 expression. Most of the positive cases (88%) had poor to moderate COX-2 staining. Dogs that had strong COX-2 expression had significantly decreased overall survival time (P = .0107). The median survival times for dogs with negative (n = 10), poor (n = 19), moderate (n = 11), and strong (n = 4) expression were 423, 399, 370, and 86 days, respectively. Additional studies are warranted to further evaluate COX-2 in osteosarcoma for its prognostic value and as a target for adjuvant therapy.

Animals↗
PubMed2005

Two cases of primary pulmonary osteosarcoma.

Two cases of primary pulmonary osteosarcoma are presented. In both cases, chest computed tomography revealed a calcified pulmonary mass and technetium-99m methylene diphosphonate bone scintigraphy showed intense uptake in the pulmonary mass. Primary pulmonary osteosarcoma was suspected on the basis of these radiographic findings. Microscopic examination of tumor specimens obtained by needle biopsy revealed histologic features of osteosarcoma, and this diagnosis was confirmed by postmortem examination of a second specimen in each case. Radiographic and histopathological findings enabled us to diagnose primary pulmonary osteosarcoma, which is one of the rarest types of cancer.

Aged↗
PubMed2006

Liposomal muramyl tripeptide phosphatidylethanolamine: Targeting and activating macrophages for adjuvant treatment of osteosarcoma.

About one third of osteosarcoma patients develop lung metastasis refractory to chemotherapy. Recent studies indicate that biological response modifiers activating the patient's immune system may help controlling minimal residual disease via pathways distinct from those used by cytotoxic drugs, and therefore prove effective against tumor resistance. Muramyl tripeptide phosphatidylethanolamine (MTP-PE) is a synthetic lipophilic glycopeptide capable of activating monocytes and macrophages to a tumoricidal state. When intercalated in multilamellar liposomes (L-MTP-PE) and injected intravenously, it targets lung, liver, and spleen macrophages. Therapeutic activity of L-MTP-PE was demonstrated in several preclinical models of experimental lung metastasis and in clinical trials in dogs with osteosarcoma. Although macrophage activation was shown to be directly involved in the in vivo anti-metastatic activity of this molecule, cytokine and chemokine secretion by activated macrophages could induce recruitment and stimulation of other immune cells, which may in turn indirectly contribute to the anti-tumor effect. L-MTP-PE has undergone clinical development in humans. In early trials, most side effects of L-MTP-PE were minimal. L-MTP-PE showed signs of efficacy in treatment of patients with recurrent osteosarcoma and the encouraging results from phase II studies led to a phase III trial conducted by the Children's Oncology Group in patients with newly diagnosed high-grade osteosarcoma. Patients were treated with or without L-MTP-PE in combination with multi-drug chemotherapy in adjuvant setting; significantly higher overall survival and disease-free survival were observed in the group receiving L-MTP-PE.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1977

Angiographic features of osteosarcoma.

Arteriography was carried out in 64 cases of pathologically confirmed osteosarcoma to evaluate the angiographic features of this lesion. This investigation proved that a variety of angioarchitectures exist in osteosarcomas, mainly related to the histologic type of tissue as well as the degree of differentiation of a tumor. Fibroblastic and chondroblastic osteosarcomas proved to be less vascular than the osteoblastic type, while the most differentiated tumor appeared to be the least vascular. This technique proved useful in choosing the proper site, or sites, for biopsy as well as for determining the intra- and extraosseous extension of the tumor. Instances were also encountered in which it was of assistance in differentiating osteosarcoma from pathologically similar bone lesions.

Angiography↗
PubMed1994

Preoperative staging of osteosarcoma: efficacy of MR imaging in detecting joint involvement.

OBJECTIVE: Selecting the appropriate surgical procedure for treatment of patients with osteosarcoma requires accurate preoperative evaluation of tumor extent. Establishing the presence or absence of joint involvement is particularly important. Accordingly, we studied the efficacy of MR imaging for detecting joint involvement in 46 patients with osteosarcoma around joint spaces. SUBJECTS AND METHODS: Preoperative MR examinations were performed in 46 consecutive patients with osteosarcoma whose tumors were located around the knee (n = 33), the hip (n = 8), or the shoulder (n = 5). T2-weighted and unenhanced and contrast-enhanced T1-weighted spin-echo MR images were obtained for all patients. We assessed the presence or absence of tumor invasion of the intracapsular-intrasynovial joint space, either by disruption of the joint capsule or by intraarticular destruction of the cortical bone and articular cartilage or the intracapsular-extrasynovial cruciate ligaments of the knee. All patients subsequently had surgery. The MR findings were correlated with findings from macroscopic and microscopic pathologic examinations. RESULTS: All 10 patients who subsequently proved to have tumor involvement of the joint were correctly identified (sensitivity, 100%). The tumor involved the knee joint in seven patients, the hip joint in two, and the shoulder joint in one. However, the MR diagnosis was false-positive in another 11 patients who did not have joint involvement at surgery (specificity, 69%). In the knee, MR imaging was more accurate in identifying tumor extension to the cruciate ligaments than to the intrasynovial joint space. Post-contrast T1-weighted images were most useful in detecting joint involvement. CONCLUSION: MR imaging is highly sensitive for detecting joint invasion of osteosarcoma. However, false-positive diagnoses may lead to overstaging of tumor and result in unnecessarily radical surgical procedures.

Adolescent↗
PubMed1995

Osteosarcoma: subtle, rare, and misleading plain film features.

Osteosarcoma is a malignant, mesenchymal, osteoid, and bone-forming tumor [1-3]. In most cases, typical radiographic features clearly illustrate the aggressive bone-forming nature of the lesion. These features include long-bone metaphyseal location, mixed areas of lysis and sclerosis, cortical destruction, periosteal new bone, and soft-tissue mass. However, numerous factors contribute to misleading radiographic patterns of osteosarcoma. They include histologic low-grade, lytic, or minimally sclerotic lesions, early detection, confinement to the intramedullary canal, benign-appearing periosteal reaction, rare intraosseous locations (subchondral, diaphyseal, intracortical), and rare skeletal sites (e.g., soft tissues, skull, ribs, tarsal bones). Secondary osteosarcomas, such as those arising from infarcts or fibrous dysplasia, may also produce a confusing radiologic picture. The purpose of this pictorial essay is to illustrate cases of osteosarcoma that proved to be difficult diagnostic dilemmas because of their subtle, rare, or misleading plain film features.

Adolescent↗
PubMed2000

Effect of all-trans and 9-cis retinoic acid on growth and metastasis of xenotransplanted canine osteosarcoma cells in athymic mice.

OBJECTIVE: To determine effects of all-trans and 9-cis retinoic acid (RA) on tumor growth and metastatic ability of canine osteosarcoma cells transplanted into athymic (nude) mice. ANIMALS: Forty-five 5-week-old female BALB/c nude mice. PROCEDURE: 1 X 10(7) POS osteosarcoma cells were transplanted subcutaneously into the intrascapular region of mice. All-trans RA (3 or 30 microg/kg of body weight in 0.1 ml of sesame oil), 9-cis RA (3 or 30 mg/kg in 0.1 ml of sesame oil), or sesame oil (0.1 ml; control treatment) were administered intragastrically 5 d/wk for 4 weeks beginning 3 days after transplantation (n = 4 mice/group) or after formation of a palpable tumor (5 mice/group). Tumor weight was estimated weekly by measuring tumor length and width, and retinoid toxic effects were evaluated daily. Two weeks after the final treatment, mice were euthanatized, and number of mice with pulmonary metastases was determined. RESULTS: Adverse treatment effects were not detected. Tumor weight was less in mice treated with either dose of 9-cis RA than in control mice, although this difference was not significant. Treatment with 30 mg of 9-cis RA/kg initiated after tumor formation significantly reduced the incidence of pulmonary metastasis, compared with the control group. CONCLUSIONS AND CLINICAL RELEVANCE: 9-cis RA decreased the incidence of pulmonary metastasis in nude mice transplanted with canine osteosarcoma cells and may be a potential adjunct therapy for treatment of osteosarcoma in dogs.

Alitretinoin↗
PubMed2000

Effects of treatment with growth hormone and somatostatin on efficacy of diammine [1,1-cyclobutane dicarboxylato (2-)-0,0']-(SP-4-2) in athymic rats with osteosarcoma.

OBJECTIVE: To determine the effect of exogenous growth hormone or somatostatin on chemotherapeutic efficacy in athymic (nude) rats with osteosarcoma. ANIMALS: 66 female athymic rats. PROCEDURE: Osteosarcoma was induced at an intratibial site. Rats were randomly allotted to 6 treatment groups. Rats were treated with saline (0.9% NaCl) solution alone, platinum, diammine [1,1-cyclobutane dicaboxylato (2-)-0,0']-(SP-4-2) (CBDCA; ie, carboplatin) plus saline solution, somatostatin alone, somatostatin plus CBDCA, growth hormone alone, or growth hormone plus CBDCA. Variables measured included estimated WBC count and percentage of neutrophils, plasma concentration of insulin-like growth factor I (IGF-I), body weight, tumor volume, weight of primary tumor, survival time, and distant metastasis at time of death. RESULTS: Tumors formed at the injection sites in all rats. Treatment with growth hormone increased, and treatment with somatostatin decreased, plasma IGF-I concentration. Treatment with growth hormone or somatostatin altered CBDCA efficacy, as determined by evaluation of mean and median survival times. Metastatic pulmonary disease developed in 63 of 64 rats. CONCLUSIONS AND CLINICAL RELEVANCE: The technique used here reliably induced local osteosarcomas and metastatic pulmonary disease. Treatment with growth hormone and CBDCA or somatostatin may improve chemotherapeutic efficacy without increasing toxic effects. IMPLICATIONS FOR HUMAN MEDICINE: Results reported here may be useful in the study of osteosarcoma in humans.

Animals↗
PubMed2002

Comparison of radiography, computed tomography, and magnetic resonance imaging for evaluation of appendicular osteosarcoma in dogs.

OBJECTIVE: To determine which imaging modality best determines the microscopic extent of primary appendicular osteosarcoma in amputated limbs in dogs. DESIGN: Case series. ANIMALS: 10 dogs with appendicular osteosarcoma. PROCEDURE: 10 dogs with appendicular osteosarcoma that did not receive neoadjuvent chemotherapy were treated by use of limb amputation. Amputated limbs were imaged by use of radiography, computed tomography (CT), and magnetic resonance imaging (MRI) and examined microscopically to determine longitudinal extent of neoplastic cell involvement and length of associated intramedullary fibrosis. Changes detected by use of the various imaging studies were compared with the actual tumor length determined microscopically. Data were analyzed to determine which imaging technique most closely predicted tumor length. RESULTS: Measurements obtained by use of craniocaudal radiographic views were most accurate at predicting tumor length but underestimated tumor length substantially in 1 limb and slightly in another limb. Measurements made by use of CT were most accurate at predicting tumor length when intramedullary fibrosis was taken into account but underestimated tumor length in 1 limb. Measurements made by use of MRI were least accurate but did not underestimate tumor length in any of the limbs. CONCLUSIONS AND CLINICAL RELEVANCE: Although radiography is used in diagnosis of osteosarcoma in dogs, additional imaging studies to confirm the extent of neoplasia prior to limb-sparing ostectomy may be beneficial. Underestimation of tumor length would be associated with higher incidence of incomplete excision and local tumor recurrence.

Amputation, Surgical↗
PubMed1983

Variation in cell surface morphology of two 90Sr-induced osteosarcomas serially transplanted in CBA mice.

The induction of skeletal tumours, which can be classified as osteosarcomas of many different types, is considered to be the primary carcinogenic effect of radiostrontium. In the present report the cell surface morphology in vivo of 90Sr-induced osteosarcoma cells was investigated, since a variety of tumour cells--and especially those investigated in vitro--have been shown to possess morphologic changes compared with their normal counterparts. Using scanning electron microscopy, variations in cell surface morphology were observed in 2 tumour series, which were serially transplanted in mice for 45 and 60 transfer generations, respectively. The slow-growing osteosarcoma cells of the early transfer generations, of osteoblastic as well as fibroblastic type, seemed to have more cytopodia than the fast-growing osteosarcoma cells from later generations. This may be due to the fact that slowly growing cell populations have a large proportion of cells in G1, in which stage there is a higher frequency of cellular cytopodia.

Animals↗
PubMed1980

Antitumor effects of doxorubicin against a virally-induced rat osteosarcoma with minimal immunosuppression.

Intratibial inoculation of a Moloney strain of Murine Sarcoma Virus (MSV-M) in neonatal Wistar-Lewis rats produced osteosarcoma in 96% of animals and resulted in a median survival of 20 days. Intraperitoneal (i.p.) administration of doxorubicin (adriamycin) (1-2 mg/kg/d, on day 10-12) resulted in reduced tumor growth and prolonged median survival to 95+ and 64 days, respectively. Higher dose doxorubicin (3-4 mg/kg/d, on day 10-12) caused early lethal toxicity. Autopsy data revealed a characteristic sarcomatous tumor producing osteoid. Gross pulmonary nodules appeared in 30% of both treated and untreated animals. Microscopic evaluation of lung tissue revealed anaplastic tumors without osteoid in as many as 90% of rats. Hepatosplenomegaly was usually present but microscopic sections of the spleen did not reveal tumor. Long bone metastases were increased in frequency in those animals receiving doxorubicin. Cell mediated immunity (CMI) to osteosarcoma cells by peripheral blood lymphocytes of tumor-bearing animals was detectable between days 21-48. This was bimodal with an early peak at day 21 (CMI = 56%) and a late peak at day 39 (CMI = 48%). CMI in rats given 1 mg/kg/d x 3d of doxorubicin was similar, with peak cytotoxicity (CMI = 61%) on day 26. Two mg/kg/d x 3d of doxorubicin did not significantly suppress either the early response (CMI = 50% on day 22) or the second peak (CMI = 38% and 50% on day 40 and 46, respectively). Thus, doxorubicin was effective in decreasing the growth of an MSV-M induced osteosarcoma and prolonging survival in the rat while usually failing to suppress CMI against rat osteosarcoma cells.

Animals↗