Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Primary neoplasms of the skeleton are rare, but metastatic involvement is, unfortunately, a common occurrence. This is particularly true for certain primary tumors. Skeletal metastases are clinically significant because of associated symptoms, complications such as pathological fracture and their profound significance for staging, treatment and prognosis. Detection of bone metastases is, thus, an important part of treatment planning. The frequency with which metastases are detected varies considerably with the type of primary tumor and with the methodology utilized for detection. Four main modalities are utilized clinically: plain film radiography, CT scan, nuclear imaging and magnetic resonance imaging. In this discussion, we will review literature on the radiology of skeletal metastases with respect to lesion detection, assessment of response to treatment and possible therapeutic implications. The bulk of the discussion will focus on MRI and nuclear studies since most of the recent advances have been made in these areas.
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PMID:Radiological imaging for the diagnosis of bone metastases. 1145 76

The bisphosphonates are potent inhibitors of osteoclast-mediated bone resorption and are now the treatment of choice for the management of hypercalcaemia of malignancy. The incidences of hypercalcaemia and other skeletal complications (bone pain, pathological fracture) remain high despite apparent responses to systemic therapy, with particularly high event rates in women with advanced skeletal metastases of breast cancer. This review focuses on studies addressing the long-term efficacy of bisphosphonates to reduce skeletal complications in breast cancer (5 studies) and multiple myeloma (4 studies), with particular reference to controlled studies of sufficient magnitude and duration to allow confidence in the estimation of efficacy. Bearing in mind the limitations of differences in trial design and the lack of direct studies comparing drugs, adequate exposure to a bisphosphonate reduces the incidence of skeletal complication by 30 to 40% in both breast cancer and multiple myeloma. Oral clondronate and intravenous pamidronate have similar efficacy in both diseases, but the duration of efficacy may differ between drugs. Both agents have shown intriguing survival benefits in subgroups of patients. The numbers needed to treat (NNT) to prevent a skeletal complication during one year are lowest in metastatic skeletal disease in breast cancer (NNT < 8) but also compare very favourably with other disease for patients with recurrent nonskeletal breast cancer or multiple myeloma (NNTs 7 to 31 depending on the complication to be prevented). Treatment costs of both breast cancer and multiple myloma are driven by inpatient and outpatient hospital visits so that bisphosphonate regimens should be developed that reduce both. Further research is required to determine if subgroups of patients can be better identified that will derive particular benefit, or perhaps no benefit at all, from bisphosphonate therapy. It is not known whether more potent bisphosphonates will deliver greater clinical efficacy in the future.
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PMID:The clinical and cost considerations of bisphosphonates in preventing bone complications in patients with metastatic breast cancer or multiple myeloma. 1151 Oct 21

Patients with cancer that has metastasized to bone will frequently develop functional problems that may respond to rehabilitative treatment. Many rehabilitation professionals, however, are concerned about the possibility of producing pathologic fracture with their treatment. Several methods have been proposed for identifying which malignant lesions in bone are at risk of fracture. In this article, these methods are reviewed and statistical analyses of them are presented. The risk of rehabilitating patients with bony metastases is also reviewed, as are the reported outcomes of these rehabilitation efforts. Standard approaches to the rehabilitation of these patients have evolved, although most of them have not been rigorously validated, and these are discussed. None of the methods for identifying lesions at risk of pathologic fracture are useful in other than long bones, and they are limited even there. The risk of producing pathologic fractures in cancer patients by increasing mobility and function, however, is low. Satisfactory outcomes have been demonstrated in attempting to rehabilitate patients who have had recent surgical repair of pathologic or impending fractures. Rehabilitation of cancer patients with bony metastases can be safely and effectively accomplished using standard approaches to the treatment of these patients.
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PMID:Bone metastasis and rehabilitation. 1151 29

Matrix metalloproteinases (MMPs) are essential in several stages of the metastatic process, and in normal bone development and remodeling. We explored whether the interaction between tumor cells and bone leads to changes in MMP and tissue inhibitor of MMP (TIMP) expression thus affecting osteolysis in metastatic bone disease. Using immunohistochemistry we have investigated the MMP/TIMP expression in tumor cells, fibroblasts, osteoblasts and osteoclasts. Thirty one specimens of bone metastasis from breast carcinoma were stained for MMP-1, -2, -9, MT1-MMP and TIMP-1, and -2 and compared with staining in normal breast tissue, primary breast carcinoma and normal bone. Specimens came from patients in three clinical scenarios: from open biopsies without or with pathological fracture, or bone marrow biopsies containing tumor from patients with pancytopenia but without clinical evidence of osteolysis. By bone histomorphometry the latter group showed a heavy tumor load not different from the open biopsy groups but displayed little active bone resorption and low numbers of osteoclasts. Cell type-specific MMP/TIMP expression was observed and the staining patterns were comparable between the three groups of patients. Though no major differences in the MMP/TIMP staining of tumor cells and fibroblasts were observed between bone metastasis and primary tumor, we showed that tumor cells do express MMPs capable of degrading bone matrix collagen. The number and activity of osteoclasts and osteoblasts was increased dramatically in bone metastases, their MMP/TIMP profiles, however, were not different from normal bone, suggesting that the mechanism of bone degradation by osteoclasts is not different from normal bone remodelling.
Clin Exp Metastasis 2000
PMID:Immunolocalization of matrix metalloproteinases and their inhibitors in clinical specimens of bone metastasis from breast carcinoma. 1159 3

Osteitis fibrosa cystica (brown tumors) can be a skeletal manifestation of advanced hyperparathyroidism, including parathyroid cancer. Severe osteitis fibrosa cystica can mimic metastatic bone diseases especially in patients with a history of cancer. Because the treatment and prognosis of these two problems differ greatly considering hyperparathyroidism in the differential diagnosis of patients found to have osteolytic lesions is critical for the appropriate management of these patients. In this case report we describe a patient with a history of renal cell cancer and presumed osteolytic bone metastases. During prophylactic intramedullary rodding to prevent pathologic fracture of her femur she was found to have a benign lesion related to her previously undiagnosed hyperparathyroidism caused by an underlying parathyroid cancer. A detailed review of this disease and the associated bone changes is also included to underscore the importance of an adequate differential diagnosis as well as optimal management. Patients with hypercalcemia or bony lesions should not automatically be treated palliatively for metastatic disease just because of a past medical history of cancer. Hyperparathyroidism is a readily curable problem if properly diagnosed.
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PMID:Disseminated brown tumors from hyperparathyroidism masquerading as metastatic cancer: a complication of parathyroid carcinoma. 1160 52

The treatment of osteosarcoma requires a multidisciplinary approach involving the family physician, orthopedic oncologist, medical oncologist, radiologist and pathologist. Osteosarcoma is a mesenchymally derived, high-grade bone sarcoma. It is the third most common malignancy in children and adolescents. The most frequent sites of origin are the distal femur, proximal tibia and proximal humerus. Patients typically present with pain, swelling, localized enlargement of the extremity and, occasionally, pathologic fracture. Most patients present with localized disease. Radiographs commonly demonstrate a mixed sclerotic and lytic lesion arising in the metaphyseal region of the involved bone. Computed tomography and bone scanning are recommended to detect pulmonary and bone metastases, respectively. Before 1970, osteosarcomas were treated with amputation. Survival was poor: 80 percent of patients died from metastatic disease. With the development of induction and adjuvant chemotherapy protocols, advances in surgical techniques and improvements in radiologic staging studies, 90 to 95 percent of patients with osteosarcoma can now be treated with limb-sparing resection and reconstruction. Long-term survival and cure rates have increased to between 60 and 80 percent in patients with localized disease.
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PMID:Osteosarcoma: a multidisciplinary approach to diagnosis and treatment. 1192 89

The aim of the current study was to determine the prognostic factors of primary osteosarcoma in adults. This is a review of 47 patients older than 40 years (27 men and 20 women) who were treated between 1977 and 1998 at the authors' institution. Tumors involved the lower limbs in 26 patients and the axial skeleton in 18 patients (38.3%). Eight patients (17%) had synchronous pulmonary metastasis and seven had a pathologic fracture before the definitive surgery. At review, 33 patients had died and 13 were alive. Twenty-one patients (44.7%) did not receive any form of systemic treatment. Tumors were treated surgically in 42 patients (89%). Local recurrence was documented in seven patients (17%). Metastasis after diagnosis appeared in 29 patients (61.7%). The 5-year disease-free survival and overall survival rates were 32.54% and 41.64%, respectively. Adult patients (> 19 years) with primary osteosarcoma had a poor clinical outcome. Metastatic disease at presentation or later, a pathologic fracture, large tumor volumes, and inadequate margins at the time of surgery were associated with significantly lower survival. The high number of adults presenting with advanced stage lesions and more tumors in the axial location might explain the high rate of recurrences. Aggressive multiagent regimens are needed to improve survival.
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PMID:Primary osteosarcoma in adults older than 40 years. 1195 95

Pathological fractures of the distal tibia as a result of cancer metastases are rare. In particular, the management of intraarticular fractures of the distal tibia has not been established. In this article, we present a case of pathological intraarticular fracture with an extensive bone defect of the distal tibia that was successfully treated by limb salvage with a locked intramedullary nail and pirarubicin-impregnated methylmethacrylate. A 52-year-old patient with duodenal cancer presented with a painful swelling in the left crus. The condition was diagnosed as an impending pathological fracture of the tibia because of cancer metastasis. During radiation therapy, an actual pathological fracture of the distal tibia occurred due to an accident. Limb-salvage surgery was performed by removing the metastatic lesion, followed by using a locked intramedullary nail. Three distal and seven proximal locking screws were inserted into the tarsal bones and the remaining tibia. About 10 cm of bone defect was reconstructed by pirarubicin-impregnated methylmethacrylate. Consequently, good stability was achieved. One month later the patient could walk without any aid. Postoperative functional score was 77% according to the Musculoskeletal Tumor Society criteria. There was no recurrence; however, the patient died of lung metastases 4 months after the limb-salvage surgery.
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PMID:Successful limb salvage of pathological fracture of the distal tibia caused by cancer metastasis. 1195 90

Pathological fractures will be encountered in increasing frequency due to more patients with cancer, surviving a longer period. The skeleton is the third most frequent localization for metastases. Breast cancer is still the most common primary tumor, but bone metastases from lung cancer seem to be diagnosed more and more. Despite of finding metastases most often in the spinal column, fractures are seen mostly at the femoral site. A pathological fracture and, in almost all cases, an impending fracture are absolute indication for operation. An exact definition of an "impending fracture" is still lacking; it is widely accepted, that 50 per cent of bone mass must be destroyed before visualization in X-ray is possible, thus defining an impending fracture. The score system by Mirels estimates the fracture risk by means of four parameters (localization, per cent of destructed bone mass, type of metastasis, pain). Improving quality of life, relieving pain, preferably with a single operation and a short length of stay are the goals of (operative) treatment. For fractures of the proximal femur, prosthetic replacement, for fractures of the subtrochanteric region or the shaft, intramedullary nails are recommended. Postoperative radiation therapy possibly avoids tumor progression. In patient with a good long term prognosis, tumor should be removed locally aggressive.
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PMID:[(Impending) pathological fracture]. 1201 95

Fibrosarcoma of bone is a relatively rare tumor; it accounts for less than 5% of bone sarcomas. The anatomical sites most commonly involved are the metaphyses of long tubular bones. Local pain, swelling, limitation of motion, and pathologic fracture are the common clinical signs and symptoms. Typical imaging findings include eccentrically located lytic lesions, with a geographic, moth-eaten, or permeative pattern of bone destruction, and extension into adjacent soft tissues. Surgery is the treatment of choice. The type of surgical procedure depends mainly on histologic grade, local conditions, and tumor location. With a high probability of metastases (>70%) after surgical treatment, perioperative adjuvant treatment modalities should be considered for high-grade tumors. The most important prognostic factors affecting survival include tumor grade, patient's age, and tumor location.
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PMID:Clinicopathologic features, diagnosis, and treatment of fibrosarcoma of bone. 1204 16


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