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We investigated the effect of dietary supplementation with isoflavones on pulmonary metastasis of B16BL6 murine melanoma cells in C57BL/6 mice. Mice were fed a basal AIN-93G diet or the basal diet supplemented with the isoflavones genistein and daidzein at 113 micromol/kg, 225 micromol/kg, 450 micromol/kg, or 900 micromol/kg for 2 wk before and after the intravenous injection of 0.5 x 10(5) melanoma cells. At necropsy, the number and size of tumors that formed in the lungs were determined. The number of mice that had >15 lung tumors was 17 in the control group, and 16, 15, 13, and 10 in the groups fed isoflavones at 113 micromol/kg, 225 micromol/kg, 450 micromol/kg and 900 micromol/kg, respectively. The latter two were significantly different from the control (P

Following an abnormal radiograph, an initial 34 patients had both computed tomography (CT) and magnetic resonance (MR) to further characterize and stage a solitary tumor. This experience determined the choice between CT and MR in evaluating the next 55 solitary tumors. The choice of examination depends on the radiologist's ability to characterize the lesion from the radiograph as to its morphology, matrix, and probable histologic nature. The anatomic location, in turn, frequently influences the ability to characterize the lesion. Lesions in long bones can almost always be successfully characterized by radiography and, in these instances, only the MR examination is required to stage the tumor. Radiographic characterization of tumors in flat bones such as the scapula, certain portions of ribs, vertebrae, and pelvis is often difficult or incomplete. In these cases, CT is the preferred initial examination, and if further staging is required to establish the relationship of the tumor to soft tissues or neurovascular structures, the MR examination is done. Because of MR's superiority in staging the tumor and CT's superiority in characterizing the lesion, the initial choice between the two examinations should depend on the radiologist's ability to characterize the lesion from the radiograph. When radiographic depiction of tumor permits assessment of its morphology, matrix and probable histologic nature, (characterization) MR ought to be the next examination solely for staging purposes. It is the anatomic location of the tumor and the radiologist's ability to characterize it that ought to govern the choice of the next examination. Surgical and histopathological findings were known in all patients in this study. [ABSTRACT FROM AUTHOR]

Early magnetic resonance (MR) experience in the evaluation of 14 consecutive long bone intramedullary osteosarcomas demonstrates the need for T1 and T2 weighted pulsing sequences in the staging of this disease. Intramedullary disease is best depicted by coronal T1 weighted pulsing sequences and subtle extra-compartmental disease by T2 weighted axial imaging. Both high intensity and low intensity intra-medullary signals were noted on T2 weighting, while all T1 weighted pulsing sequences showed intra-medullary disease to have low signal intensity. Extraosseous tumor on T2 weighting usually had a high signal, and disease extent was therefore sharply demarcated from uninvolved muscle and its relationship to vessels confidently assessed. MR appears optimally suited for local staging of osteosarcoma, further enhancing the role of radiology in planning limb-salvage surgical techniques. [ABSTRACT FROM AUTHOR]

On T1 weighted pulsing sequences, the majority of soft tissue masses are of low signal intensity and show high intensity signals on T2 weighting. There however is a subset of soft tissue masses of varied histology that shows high signal intensity on T1 weighted pulsing sequences. These masses have either fat or blood in their substance. Lipomatous and hemangiomatous lesions that did not show high-signal intensity on T1 weighting were also encountered and are discussed. Present experience with MRI of soft tissue masses suggests that there is a limited spectrum of entities that produce high-signal intensity T1 weighted soft tissue masses. [ABSTRACT FROM AUTHOR]

Three patients with histologically differing lesions of synovial origin and two with synovial cysts, one of which was a dissecting popliteal cyst, were examined by magnetic resonance imaging (MR) and computerized tomography (CT). The three histologically proven synovial lesions were synovial sarcoma, diffuse giant cell tumor of tendon sheath, and synovial chondromatosis. In two of the five patients MR provided better anatomic and morphologic appreciation than CT, while in the others they were of equal value. CT demonstrated calcification in two of the lesions while on MR calcification could be identified in only one patient where it outlined the mass. MR did not demonstrate calcification in the substance of the diffuse giant cell tumor of tendon sheath. Coronal, transverse, and sagittal images of magnetic resonance graphically demonstrated the extent of the soft tissue masses and their relationship to bone, vessels, and soft tissue structures. Synovial sarcoma had a shorter T1 than diffuse giant cell tumor of tendon sheath (these two lesions being of comparable size) and also had a uniformly longer T2. The dissecting popliteal cyst showed the most intense signals on the T1 weighted images, while the uncomplicated synovial cyst showed a long T1. On the T2 weighted images, each type of cyst showed a long T2. The variance and overlap of intensity of MR signals suggest limited specificity in predicting the histologic nature of the synovial lesion. [ABSTRACT FROM AUTHOR]

Experimental models were created in rat fibula to represent impaired bone healing so that biological deficiencies that cause bone repair to fail or to be delayed may be investigated. These models consist of a 4-mm-long segmental defect, created in rat fibula by osteotomy, and fitted with a 7-mm-long tubular specimen of demineralized bone matrix (DBM) over the cut ends of the fibula. The experiments in this study involved various modifications of the DBM scaffold designed to reduce its osteoinductive activity: steam sterilization (sDBM), ethylene oxide sterilization (eoDBM), trypsin digestion (tDBM), and guanidine hydrochloride extraction (gDBM). Bone healing was evaluated by bending rigidity of the fibula and mineral content of the repair site at 7 weeks post-surgery. The sDBM scaffolds resorbed completely by 7 weeks and hence this model was a nonhealing negative control. Rigidities in the unmodified DBM and tDBM groups were comparable, whereas in the gDBM and eoDBM groups it was significantly reduced. Histologically, in the 4-mm defects repaired with unmodified DBM, direct and endochondral bone formation in the scaffold and the defect resulted in a neocortex consisting of woven and lamellar bone uniting the broken bone by 7 weeks post-surgery. We conclude that the eoDBM and gDBM groups represent failure or delay of the bone repair process when compared with the unmodified DBM group in which the process is analogous to normal bone healing.

The present study is a retrospective review of the treatment of 12 humeral shaft nonunions by using an intramedullary allograft with compression plating. The average age of the patients was 61 years (range, 36-82 years). Eight cases involved the proximal shaft, 3 cases were at the mid-diaphyseal level, and 1 case was at the distal one third. Follow-up averaged 30 months (range, 12-96 months). Ten patients (83%) went on to uneventful healing at an average of 3 months after surgery. Two failures involving patients with multiple medical conditions occurred secondary to reinjury. Two cases of postoperative radial nerve neuropraxia involved the posterior approach to the humerus. Each resolved with no long-term residual morbidity. One patient developed postoperative adhesive capsulitis of the shoulder that resolved with nonoperative treatment. We feel that a fibular allograft, along with compression plating, can give satisfactory results for humeral shaft nonunions. This technique can be especially helpful in proximal humeral nonunions and in nonunions involving osteoporotic bone. Patients with multiple medical problems at risk for refalls should be protected until complete healing has occurred.

Bone repair models in animals may be considered relevant to human fracture healing to the extent that the sequence of events in the repair process in the model reflect the human fracture healing sequence. In the present study, the relevance of a recently developed segmental defect model in rat fibula to human fracture healing was investigated by evaluating temporal progression of rigidity of the fibula, mineral content of the repair site, and histological changes. In this model, a surgically created 2-mm-long defect was grafted with a 5-mm-long tubular specimen of demineralized bone matrix (DBM) by inserting it over the cut ends of the fibula. The temporal increase in rigidity of the healing fibula demonstrated a pattern similar to biomechanical healing curves measured in human fracture healing. This pattern was characterized by a short phase of rapidly rising rigidity during weeks 4-7 after surgery, associated with a sharp increase in the mineral content of the repair tissue. This was preceded by a phase of nearly zero rigidity and followed by a phase of slow rate of increase approaching a plateau. Histologically, chondroblastic and osteoblastic blastema originating from extraskeletal and subperiosteal (near fibula-graft junction) regions, infiltrated the DBM graft during the first 2 weeks. The DBM graft assumed the role of a "bridging callus." By weeks 6-8, most of the DBM was converted to new woven and trabecular bone with maximal osteoblastic activity and minimal endochondral ossification. Medullary callus formation started with direct new bone formation adjacent to the cortical and endosteal surfaces in the defect and undifferentiated cells in the center of the defect at 3 weeks. The usual bone repair process in rodents was altered by the presence of the DBM graft to recapitulate the sequential stages of human fracture healing, including the formation of a medullary callus, union with woven and lamellar bone, and recreation of the medullary canal.

Morbidity resulting from the toxicity of chemotherapeutic drugs suggests that novel approaches are worthy of investigation. Development of the use of low intensity magnetic fields as an adjuvant to current treatment regimens to prevent metastatic disease may prove to be efficacious. Using a cell culture model, we have developed a magnetic field (MF) treatment that offers the possibility of lowering the therapeutic dose of these drugs and thereby reducing morbidity. Our studies have found that a low intensity (approximately 2 gauss) MF signal and a relatively low dose (0.1 microg/ml) of Adriamycin (ADR) inhibited proliferation of human osteosarcoma cells by 82%, whereas the MF and ADR acting individually caused only 19% and 44% inhibition, respectively.

The present study investigated the effect of dietary supplementation of selenomethionine on pulmonary metastasis of B16BL6 murine melanoma cells in C57BL/6 mice. Mice were assigned to four groups of 15 each. They were fed a basal AIN93G diet and the basal diet supplemented with 2.5 ppm or 5 ppm selenium as selenomethionine or with 2.5 ppm selenium as selenite for two weeks before and after the intravenous injection of 0.5 x 10(5) tumor cells. At necropsy, the number and size of tumors that developed in the lungs were determined. The number of mice that had > or = 11 tumors was 13, 8, 8, and 6 (p < 0.02 compared with the control), and the median number of lung tumors was 64, 14, 12 (p < 0.05 compared with the control), and 8 (p < 0.01 compared with the control) in the control group and the groups with 2.5 ppm and 5 ppm selenium as selenomethionine and 2.5 ppm selenium as selenite. Dietary supplementation of selenomethionine decreased tumor cross-sectional area and tumor volume compared with the controls. At the same dietary level, selenite had a greater inhibitory effect on tumor size than selenomethionine. These results demonstrate that dietary supplementation of selenomethionine reduced experimental metastasis of melanoma cells in mice and inhibited the growth of metastatic tumors that formed in the lungs. It is concluded that selenomethionine is an active form of selenium that reduces experimental metastasis.

Hyperparathyroidism is commonly seen in patients with end-stage renal disease and less commonly in the primary form. The skeletal manifestations of hyperparathyroidism are the same in both forms and are well described in the literature. We treated a patient from each category. Multiple bony lesions and pathologic fractures were observed. The clinical presentations and radiologic and histologic findings confirmed the diagnosis of hyperparathyroidism and osteitis fibrosa cystica in both patients. Subtotal excisions of the parathyroid glands were done in both patients. Appropriate treatment of the bony lesions and pathologic fractures resulted in healing. Histologic evaluation of the bony lesions indicated an osteoblastic or healing response. The reversal of the histologic pattern in just 5 days and 16 days after parathyroidectomy was noted. In treating such patients, physicians should consider parathyroidectomy as an aid in the overall management of patients.

The purpose of the present study was to determine the effect of dietary supplementation of soybean protein isolate (SPI) on experimental metastasis of B16BL6 murine melanoma cells in C57BL/6 mice. Four groups of mice were fed a basal AIN-93G diet or the basal diet supplemented with 10%, 15%, or 20% SPI for two weeks before and after the intravenous injection of 0.75 x 10(5) cells. At necropsy the number of tumors that developed in the lungs and their cross-sectional area were determined, and tumor volume was calculated. In the control group, 12 of the 15 mice had > or = 11 lung tumors. In contrast, only 3 or 4 of the 15 mice fed the SPI diets had > or = 11 tumors. The incidence of metastasis was 93%, 60%, 53%, and 53%, and the median number of lung tumors was 53, 2, 2, and 1 in mice fed the basal, 10%, 15%, and 20% SPI diets, respectively. Tumor cross-sectional area and tumor volume of SPI groups were significantly decreased compared with the controls. These results demonstrate that dietary supplementation of SPI reduced pulmonary metastasis of B16BL6 cells in mice and inhibited the growth of tumors that developed in the lungs. It is concluded that soybeans may be a useful adjuvant for preventing metastatic diseases in cancer patients.

The purpose of the present study was to determine the effect of dietary supplementation of selenite on experimental pulmonary metastasis of B16BL6 murine melanoma cells in C57BL/6 mice by means of an intravenous injection model. Three groups of mice were fed a basal AIN-93G diet containing 0.1 ppm selenium (control group) or the basal diet supplemented with 2 or 4 ppm selenium as selenite (experimental groups). Mice were fed the diet for two weeks before and after the intravenous injection of 0.75 x 10(5) viable tumor cells. At necropsy the number of tumors that developed in the lungs and their cross-sectional area were determined, and tumor volume was calculated. In the control group, 12 of the 15 mice had > or = 1 lung tumors. In contrast, only 4 of the 15 mice in each of the selenite-supplemented groups had > or = 11 tumors. The incidence of metastasis in mice fed the control and the 2- and 4-ppm selenium diets was 93%, 73%, and 53%, respectively. The median number of lung tumors was 53, 1, and 1 in mice fed the basal and the 2- and 4-ppm selenium diets, respectively. Tumor cross-sectional area and tumor volume were significantly decreased in selenite-supplemented groups. These results demonstrate that dietary supplementation of selenite reduced pulmonary metastasis of B16BL6 melanoma cells in C57BL/6 mice and also inhibited the growth of the metastatic tumors that developed in the lungs. It is concluded that selenite may be a useful adjuvant to prevent metastatic diseases in cancer patients.

Malignant neoplasms of the geriatric skeleton are either primary or metastatic in nature. The vast majority are metastatic to the skeleton from carcinomas. Rarely, a primary skeletal malignancy, usually a chondrosarcoma or a malignant fibrous histiocytoma, develops in the geriatric patient. This article discusses the presentation, evaluation, and management of these patients. Illustrative cases are presented.

Fat embolization syndrome is a well-known complication associated with total hip arthroplasty. It is believed to be caused by high intramedullary pressures that occur during cement pressurization and femoral stem placement. Fat embolization syndrome has also been reported with intramedullary reaming and placement of an intramedullary alignment guide during total knee arthroplasty. To our knowledge, there have not been previous reports of fatal fat emboli as a result of uncemented hip arthroplasty. The purpose of this case report is to describe a fatality due to fat embolization following a noncemented bipolar arthroplasty.

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.

Primary lymphoma of bone is a rare clinical entity that accounts for less than one per cent of all non-Hodgkin's lymphomas. Although they occasionally present as a solitary lesion in bone, lymphoma involving bone is a manifestation of disseminated disease in many instances. All patients initially found to have a solitary lymphoma of bone need to be thoroughly investigated for systemic disease because more than half of the patients presenting with initially solitary bone lesions are found to have systemic disease involving lymph nodes and/or other organs. Choice of therapeutic management is based on the stage of disease. Stage I-E primary lymphoma of bone can be controlled in 70-90% of cases using local radiation therapy alone if adequate radiation doses are used. Patients with advanced disease should be treated with combination chemotherapy in addition to local radiotherapy. Loeffler et al reported long-term survival results of 90% 8-year actuarial overall survival rate for children with primary lymphoma of bone who received combined therapy with radiation and chemotherapy (adriamycin, prednisone and oncovin). The actuarial lymphoma-free survival rate was 100% at eight years. Regardless of stage of the disease, radiation treatment to the primary tumor appears to be critical for adequate local control of disease as well as rapid symptomatic relief.

Three murine hybridomas (TMMR-1-3) were developed by repeated immunizations of mice with four different human osteosarcoma cell lines in an alternating sequence of inoculations. The monoclonal antibodies were screened for reactivities to cultured cell lines and tissue sections of osteosarcomas using flow cytometry and immunohistochemical techniques. TMMR-2 is a highly specific antibody (IgG1) that reacted with all 14 osteosarcoma tumors and eight human osteosarcoma cell lines tested, including the established human osteosarcoma cell lines HOS and Saos-2. Benign neoplastic cells from two osteoblastomas, osteoblasts from regions of reparative osteoid formation and neonatal new bone, are also reactive with TMMR-2. TMMR-1 has mesenchymal specificity while TMMR-3, although reactive with osseous differentiated cells, also reacted with mitotic cells of all cell types. Characterization of antigen structure by Western immunoblotting revealed that TMMR-2 reacted with a 100 degrees C heat labile mercaptoethanol-sensitive Mr 26,000 protein, and TMMR-3 recognized a mercaptoethanol-resistant Mr 97,000 protein whereas TMMR-1 reacted with a series of bands from 65,000 to 85,000 molecular weight, all of which were mercaptoethanol sensitive. TMMR-1 and TMMR-2 monoclonal antibodies showed complement-independent inhibition of [3H]thymidine incorporation into DNA, but did not exhibit cytotoxic activity. The results suggest that TMMR-2 is a specific antibody that recognizes an osteoblast/osteocyte surface antigen present in normal, reactive, and neoplastic disorders of bone. The inhibitory effects on DNA synthesis in cultured osteosarcoma cells by TMMR-2 indicate an important cell growth/proliferation role of this surface antigen. These monoclonal antibodies, in combination with other known antibodies, can be used to characterize mesenchymal cell surface antigenic structure and differentiation.

Oncogenic osteomalacia is a rare condition characterized by the development of pain and fractures in a patient with specific laboratory abnormalities consisting of hypophosphatemia, hyperphosphaturia, and decreased 1,25-OH vitamin D levels. The clinical scenario is completed by the association of this osteomalacic state with the finding of a neoplastic process in the afflicted patient. The authors report a patient in whom the diagnosis of oncogenic osteomalacia was established and treatment begun despite the fact that the associated tumor (benign undifferentiated tumor of meschymal origin) escaped detection for many months. Following discovery of the tumor and identification by magnetic resonance imaging, the patient was cured by surgical resection.

Most soft-tissue masses and tumors of various etiologies and histologies have high signal intensity on T2-weighted pulse sequences (long T2). Of 47 soft-tissue masses, seven had a low signal (short T2) on T2-weighted pulse sequences. All seven masses were tumors, and histologic review showed that their composition differed from that of the other 40 lesions with a long T2 in that the seven masses were relatively acellular and had more collagen. The tumors with a short T2 included one malignant and six benign soft-tissue tumors. Malignant fibrous histiocytoma and aggressive fibromatosis showed paradoxical signal intensities in that they showed both long and short T2. All of the tumors with low signal intensity on T2-weighted images had significant fibrous elements and marked hypocellularity. This study suggests that the less commonly encountered short T2 may be seen in both benign and malignant soft-tissue lesions. A part of the explanation for the low signal on T2-weighted sequences appears to be the relative acellularity and abundant collagen of these tumors in comparison with those that have the same histologic diagnoses but show a high signal. The histologic composition of the tumor rather than the histologic diagnosis appears to influence the MR signal on T2-weighted sequences.

Fifty-three histologically confirmed soft tissue masses in 48 patients were evaluated by magnetic resonance imaging (MR) and computerized tomography (CT). Twenty-three of these were malignant, twenty-three benign and seven of intermediate malignancy (all aggressive fibromatosis). The two procedures were compared for sensitivity and delineation of masses, their relationship to important neurovascular structures, their potential for histological diagnoses, their relative roles in influencing the surgical approach and the preferred modality in the follow-up for detection of tumor recurrence. Both modalities have their relative strengths and weaknesses. However, the superior contrast resolution of magnetic resonance imaging, its demonstration of lesions not clearly identified by CT, its pluridirectional capabilities and its ability to demonstrate large soft tissue tumors in a single coronal or sagittal plane makes it the preferred initial modality for evaluation of the soft tissue tumor of uncertain etiology and also in the follow-up of these patients. Despite MR's superiority in anatomically staging soft tissue tumors it, like CT, is of limited value in characterizing soft tissue sarcomas.

The pathophysiology and pathologic appearances of adult osteomyelitis are discussed, without reference to childhood hematogenous (metaphyseal) osteomyelitis or chronic osteomyelitis secondary to vascular phenomena such as diabetes or arteriosclerosis. Osteomyelitis as a feature of generalized sepsis in the immunocompromised patient is also excluded. The focus is on infection of the adult skeleton that occasionally arises spontaneously but more commonly presents as a complication of an open fracture or an operative procedure. The special features of adult osteomyelitis that are the result of the infection developing within the confined and rigid structure of the skeleton are highlighted. Lastly, the histopathology of osteomyelitis is examined in an effort to demonstrate the host bone's response to this injury.

In this review are discussed a small group of bone tumors that present the greatest and sometimes unresolved problems in diagnosis, not only for the clinician but also for the pathologist, even with full knowledge of the clinical and roentgenologic presentation. The following neoplastic lesions are described in detail: cartilage-forming tumors, bone-forming tumors (with special emphasis on aggressive or malignant osteoblastoma), and round-cell tumors of bone. This last group presents a special challenge to the pathologist even after histopathologic examination. Some newer, more sophisticated methods are discussed, especially those applied in the differential diagnosis of Ewing's sarcoma and tumors of neuroectodermal origin.