Joint replacement surgery--sooner rather than later?
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Arthroplasty, Replacement↗
Biomedical subjects
P F Choong
Publications and source records attributed to P F Choong.
Bisphosphonates regulate cell growth and gene expression in the UMR 106-01 clonal rat osteosarcoma cell line.
Local growth of osteosarcoma involves destruction of host bone by proteolytic mechanisms and/or host osteoclast activation. Osteoclast formation and activity are regulated by osteoblast-derived factors such as the osteoclast differentiating factor, receptor activator of NF-kappaB ligand (RANKL) and the inhibitor osteoprotegerin (OPG). We have investigated the in vitro effects of bisphosphonates on a clonal rat osteosarcoma cell line. The aminobisphosphonate pamidronate was added to UMR 106-01 cell cultures (10(-8)M to 10(-4)M up to 5 days). The non-aminobisphosphonate clodronate was administered for the same time periods (10(-6)M to 10(-2)M). Cell proliferation, apoptosis and mRNA expression was assessed. Both agents inhibited cell proliferation in a time- and dose-dependent manner. ELISA analysis demonstrated an increase in DNA fragmentation although there was no significant dose-related difference between the doses studied. Bisphosphonate-treated cultures had a greater subpopulation of cells exhibiting morphological changes of apoptosis. Expression of mRNA for osteopontin and RANKL was down-regulated by both agents, while the expression of mRNA for alkaline phosphatase, pro-alpha1(I) collagen and OPG was not altered. Out in vitro work suggests the bisphosphonates not only have direct effects on osteosarcoma cell growth and apoptosis, but also, by altering the relative expression of osteoclast-regulating factors, they may inhibit the activity of osteoclasts and their recruitment.
Animals↗
Is radiotherapy important for low-grade soft tissue sarcoma of the extremity?
Radiotherapy and limb-preserving surgery has replaced amputation and compartmental resection for treatment of soft tissue sarcomas. However, the role of radiotherapy in low-grade tumors remains unclear. This study reviews the outcomes of 132 patients who received multimodality treatment for low-grade soft tissue sarcoma. Large primary tumors (> 5 cm) and the absence of radiotherapy correlated with local recurrence. Radiotherapy was most effective in patients operated on with marginal margins. Patients who were treated with wide surgical margins or had small tumors (< or =5 cm) showed no benefit with adjuvant radiotherapy. Size greater than 5 cm and local recurrence correlated with metastasis. Radiotherapy appears to be important in the management of low-grade soft tissue sarcoma. The principles of local treatment for low-grade soft tissue sarcoma should be the same as for high-grade tumors with a combination of surgery and adjuvant radiotherapy. In a subset of patients with small and widely excised tumors, consideration may be given to withholding radiotherapy. Local recurrence and metastasis from low-grade soft tissue sarcoma may occur as long as 1 decade after primary tumor resection. Long-term review of patients with low-grade tumors may be indicated.
Adolescent↗
Adamantinoma and meningioma occurring synchronously in a patient with breast cancer: a case report.
Screening mammography of a woman with no symptoms led to the diagnosis of carcinoma of the breast, an intracranial meningioma, and adamantinoma of the right tibia. This is the first reported case of three synchronous primary tumors of different tissue origins. Biopsy is essential for diagnosing or excluding primary tumor(s) in cases of suspected metastases occurring at a limited number of sites.
Bone Neoplasms↗
The expression of the urokinase plasminogen activator system in metastatic murine osteosarcoma: an in vivo mouse model.
The role of urokinase plasminogen activator (uPA) in osteosarcoma is poorly understood. We examined the importance of uPA, its receptor, uPAR, and its inhibitor, PAI-1, in our in vivo model of metastatic osteosarcoma. Rodent osteosarcoma cells (UMR 106-01) were inoculated into the tibia of athymic mice. Animals were sacrificed and autopsied at 4 days to 5 weeks after inoculation. Tibiae and lungs were excised, fixed, and examined histologically and by in situ hybridization. Osteosarcoma development was associated with tibial swelling and lameness, and radiographic changes included osteolysis and new bone formation. Lung metastases developed spontaneously. In the tibial tumors, uPAR mRNA was expressed early (4 days), whereas uPA and PAI-1 mRNA increased as the tumor invaded the surrounding tissue (3 weeks). There was also an increase in the mRNA expression of the osteoblast-related genes, alpha1(I) procollagen and osteopontin, but not matrix Gla protein. Lung metastases also expressed mRNA for the uPA system and the bone-related proteins. We have produced a model of metastatic osteosarcoma, which typifies the characteristics of the human tumor. Our results suggest that the uPA system plays a role in the local aggressiveness and metastasis of osteosarcoma and, in particular, indicates a possible therapeutic role for uPAR antagonists in the treatment of osteosarcoma.
Animals↗
Clinical pathway for fractured neck of femur: a prospective, controlled study.
OBJECTIVE: To assess outcomes of using a clinical pathway for managing patients with fractured neck of femur. DESIGN: Prospective, pseudorandomised, controlled trial. SETTING: St Vincent's Hospital, Melbourne, Victoria (a tertiary referral, university teaching hospital), 1 October 1997 to 30 November 1998. PARTICIPANTS: 111 patients (80 women and 31 men; mean age, 81 years) admitted via the emergency department with a primary diagnosis of fractured neck of femur. INTERVENTIONS: Management guided by a clinical pathway (55 patients) or established standard of care (control group, 56 patients). MAIN OUTCOME MEASURES: Timing of referrals and discharge planning; total length of stay; and complication and readmission rates within 28 days of discharge. RESULTS: Patients managed according to the clinical pathway had a shorter total stay (6.6 versus 8.0 days; P = 0.03), even if assessment for placement by the Aged Care Assessment Service was required (9.5 versus 13.6 days; P = 0.03). There were no significant differences in complication and readmission rates between pathway and control patients (complication rates, 24% versus 36%; P = 0.40; readmission rates, 4% versus 11%; P = 0.28). CONCLUSION: Coordinated multidisciplinary care of patients with fractured neck of femur reduces length of stay without increasing complications.
Aged↗
Urokinase plasminogen activator system gene expression is increased in human breast carcinoma and its bone metastases--a comparison of normal breast tissue, non-invasive and invasive carcinoma and osseous metastases.
The urokinase plasminogen activator (uPA) system has been widely associated with the development of breast carcinoma. However, the role of the urokinase pathway in the development of osseous breast cancer metastases has been largely overlooked. We studied the expression of uPA, urokinase plasminogen activator receptor (uPAR)- and plasminogen activator inhibitor type-1 (PAI-1) in human breast carcinomas and their bone metastases, using in situ hybridisation. Studies were performed using paraffin-embedded tissue from 13 ductal carcinomas, 23 invasive ductal carcinomas, five normal breasts and 25 bone metastases. The majority of the tumours examined expressed low to moderate levels of uPA mRNA and low to high levels of uPAR and PAI-1 mRNA, which was predominantly localised to the epithelial tumour cells. There was slight over-expression of uPA and PAI-1 mRNA and a marked increase in uPAR mRNA expression in the malignant tumours compared with benign tissue. Overall, uPAR and PAI-1 mRNA expression was found to be more variable than uPA mRNA, suggesting a possible role of the receptor and inhibitor in the regulation of uPA activity. Increased alpha1(I) procollagen (COL) and osteopontin (OPN) mRNA expression was detected, primarily in the stromal cells, in malignant tumours compared with the benign tissue. The increased expression of the components of the uPA system on the epithelial tumour cells may account for the activation of the proteolytic cascade that occurs during breast cancer metastasis to bone. Furthermore, the over-expression of COL and OPN suggests a possible interaction between these matrix proteins and the uPA system.
Bone Neoplasms↗
Major reconstruction for periacetabular metastasis: early complications and outcome following surgical treatment in 40 hips.
We performed 40 total hip arthroplasties with pelvic reconstruction in 37 patients with metastatic periacetabular tumor. 3 patients underwent bilateral periacetabular reconstructive surgery and 2 of these had bilateral procedures at the single operation. There were 8 Harrington class I, 7 class II, and 25 class III lesions. A modified Harrington procedure was employed. All patients showed improvements in hip pain, analgesic use, ambulation and mobility postoperatively. 1 prosthetic dislocation occurred after a fall at home 2 months following surgery. 2 patients had pulmonary emboli during the femoral procedure, 1 of whom died during surgery. There were no prosthetic loosenings. Preoperative CT and/or MRI are important for the study of metastatic involvement of acetabular bone. Durability of reconstruction requires appropriate use of acetabular mesh, Steinmann pins, acetabular reinforcement rings and long-stem femoral prostheses. Careful patient selection may improve quality of life. A sequential bilateral procedure should be considered for some patients.
Acetabulum↗
Large tumor endoprostheses and extracortical bone-bridging: 28 patients followed 10-20 years.
Aseptic loosening is a common cause of failure in large tumor endoprostheses. The concept of extracortical bone-bridging was developed to tackle the problem of loosening. New bone which forms across the junction of the bone-prosthesis junction is believed to improve fixation by controlling the transfer of stresses across the junction as well as by giving additional stability to the prosthesis. We present the long-term experience with this concept following major reconstruction after tumor and non-tumor conditions in 31 patients. The overall function was good for upper and lower limb prostheses. Most patients had extracortical bone bridging which was maintained for over 10 years. In 1/3 of patients this involved over 75% of the prosthetic circumference. Prosthetic survival was best with intercalary devices, followed by proximal femoral and distal femoral prostheses. Survival of prostheses in young active patients was similar to that reported in older patients undergoing primary joint replacement.
Adolescent↗
The incidence of acute cardiorespiratory and vascular dysfunction following intramedullary nail fixation of femoral metastasis.
Intramedullary nail fixation is a common treatment for metastatic tumors of the femur with overt or impending femoral fracture. This procedure sometimes causes severe cardiorespiratory and vascular dysfunction. The clinical relevance of this is not dear. We reviewed 45 operations in 43 patients, where intramedullary nail fixation was used to treat metastatic femoral fractures and impending fractures. We studied the incidence of intraoperative oxygen desaturation and hypotension associated with intramedullary manipulation as markers of cardiorespiratory and vascular dysfunction. Acute oxygen desaturation and hypotension occurred in 11 of our 45 patients. Of these, 3 died, 2 required intensive care postoperatively and 6 made uneventful recoveries. We hope to highlight a serious complication in this patient group.
Acute Disease↗
Clinical pathways in hip and knee arthroplasty: a prospective randomised controlled study.
OBJECTIVE: To ascertain the effectiveness of clinical pathways for improving patient outcomes and decreasing lengths of stay after hip and knee arthroplasty. DESIGN AND SETTING: Twelve-month randomised prospective trial comparing patients treated through a clinical pathway with those treated by an established standard of care at a single tertiary referral university hospital. PARTICIPANTS: 163 patients (56 men and 107 women; mean age, 66 years) undergoing primary hip or knee arthroplasty, and randomly allocated to the clinical pathway (92 patients) and the control group (71 patients). MAIN OUTCOME MEASURES: Time to sitting out of bed and walking; rates of complications and readmissions; match to planned discharge destination; and length of hospital stay. RESULTS: Clinical pathway patients had a shorter mean length of stay (P = 0.011), earlier ambulation (P = 0.001), a lower readmission rate (P = 0.06) and closer matching of discharge destination. There were beneficial effects of attending patient seminars and preadmission clinics for both pathway and control patients. CONCLUSION: Clinical pathway is an effective method of improving patient outcomes and decreasing length of stay following hip and knee arthroplasty.
Activities of Daily Living↗
Osteosarcoma of the scapula arising in osteogenesis imperfecta.
A case of osteosarcoma arising in the scapula of a 37 year old woman with severe congenital sporadic white sclera type osteogenesis imperfecta (OI) is presented. Osteosarcoma occurs as a sporadic rather than a related occurrence in patients with OI. A delay in the diagnosis of osteosarcoma may occur due to the similarity in symptomatology between the two conditions and because of the difficulty in differentiating between hyperplastic callus and tumor using conventional radiographic imaging techniques.
Adult↗
Osteosarcoma of the foot: a review of 52 patients at the Mayo Clinic.
This is a review of 52 osteosarcomas of the foot. The incidence of osteosarcoma of the foot is very low. It appears to affect older patients and the calcaneus is a common site. The incidence of chondroblastic tumors is high and most tumors are high grade. In many cases, amputation is required for local control of disease.
Adolescent↗
The role of allografts in tumour surgery.
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Arthrodesis↗
An audit of early hospital readmission after primary knee joint replacement.
BACKGROUND: Hospital readmissions following arthroplasty represent a considerable burden to the community. The present study investigates the magnitude of this problem and the reasons for early readmission. METHODS: The medical records of patients who underwent primary knee joint replacements between July 1989 and December 1994 were reviewed retrospectively. Readmission within 12 months of surgery was noted and the prognosis of these patients assessed. RESULTS: A total of 160 patients (180 arthroplasties) were appropriate for review. The readmission rate for knee-related morbidity was 18%. The main reasons for this included pain, stiffness, and the investigation/management of an inflamed joint. Notably, patellofemoral disease was common, particularly in the group without resurfaced patellae, manipulation of a stiff joint was rarely effective unless instituted early and aetiologies aside from sepsis often resulted in the patient returning with an inflamed joint. CONCLUSIONS: Readmission is a significant problem which heralds a poor 12-month prognosis.
Adult↗
Musculoskeletal oncology--advances in cytogenetics and molecular genetics and their clinical implications.
Although musculoskeletal malignancies comprise a small group of cancers, a vast number of histological subtypes have been identified attesting to the heterogeneity of this class of tumours and the growing interest in their development. The mode of management for both bone and soft tissue sarcomas has been examined extensively and treatment guidelines have been proposed. Despite the intensive study and multidisciplinary treatment, a substantial proportion of tumours remain recalcitrant to therapy and recur locally and systemically. Improved methods of characterising these tumours may help in understanding their biology. Cytogenetic and molecular genetic techniques allow a subcellular dissection of these malignancies which may aid the identification of mechanisms that are important in tumorigenesis. Already candidate genes have been isolated which may play an important role in the deregulation of proliferation and or the adoption of a malignant phenotype, features which are fundamental in tumour development. By studying the molecular biology and cytogenetics of tumours it may be possible to improve diagnostic and prognostic accuracy thereby minimising over and under treatment.
Bone Neoplasms↗
Epithelioid hemangioendothelioma of bone.
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Adult↗
Urokinase-plasminogen-activator levels and prognosis in 69 soft-tissue sarcomas.
The local and systemic invasiveness of soft-tissue sarcomas may depend upon an interaction between the primary tumour and the extracellular matrix in which the proteolytic enzyme, urokinase plasminogen activator (uPA), may have an important role. We analyzed the expression of uPA in soft-tissue sarcoma using a luminescent immunoassay technique, and examined the relationships between different uPA levels and tumour characteristics and behaviour. We evaluated 69 adult patients with surgically treated soft-tissue sarcomas (MFH 43, leiomyosarcoma 8, liposarcoma 5, synovial sarcoma 4, others 9) of the extremities and trunk wall. Sixteen developed local recurrences, 26 developed metastases, and 5 had both. The median follow-up for survivors was 55 (30-80) months. The median uPA level was 1.4 (0.04-10.6) ng/mg protein. Increasing uPA levels correlated with increasing grade, malignant fibrous histiocytomas, leiomyosarcomas, DNA non-diploidy, tumour necrosis, local recurrence, and metastasis. Storiform-pleomorphic MFH had higher uPA levels than the myxoid variant. A cut-off value of 0.25 ng/mg protein was identified, above which local recurrence and metastasis occurred more frequently. High uPA levels appear to reflect the malignant phenotype in soft-tissue sarcoma, thus supporting the role of uPA as a prognostic indicator.
Adult↗