Surgery (St Vincent's) - Research Publications
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ItemNo Preview AvailableClinical applications of molecular imaging in sarcoma evaluation.(E-MED LTD, 2005-06-21)A wide range of molecular imaging techniques are available that can provide complementary information to conventional, anatomical imaging for the evaluation of known or suspected bone and soft tissue sarcomas. In particular, positron emission tomography (PET), particularly in the form of hybrid PET/CT technology, offers many potential advantages over current imaging approaches by delineating not only the extent of disease but also the biological heterogeneity that can exist both between and within sarcomas. This review discusses the clinical situations where nuclear medicine techniques can aid in the management of patients with sarcoma. These include biopsy guidance, whole body staging, therapeutic response assessment and evaluation of residual mass lesions after treatment.
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ItemBisphosphonates regulate cell growth and gene expression in the UMR 106-01 clonal rat osteosarcoma cell line(NATURE PUBLISHING GROUP, 2001-04-06)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.
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ItemOutcome of patients with osteosarcoma over 40 years of age: is angiogenesis a marker of survival?(Springer Science and Business Media LLC, 2006-03-21)BACKGROUND: Osteosarcoma predominantly afflicts young people in their second and third decades of life. When osteosarcoma arises in patients older than 40 years, the prognosis is usually poorer compared to their younger counterparts. Although the clinical, histopathologic features and prognostic indicators are well defined for young patients, much less is known about affected adults. The purpose of this study is to describe our institution's experience with the management of osteosarcoma in patients greater than 40 years and also evaluate, by immunohistochemical analysis, the prognostic significance of microvessel density, as a marker of intratumoural angiogenesis. METHODS: A retrospective clinicopathological analysis was performed on 11 patients over the age of 40 years that were treated at our institution between 1996 and 2004. Archival pre-treatment biopsy tissue was retrieved for immunohistochemical staining against two endothelial cell markers (CD31 and CD34) and also against VEGF. Angiogenesis was assessed by determining the intratumoural microvessel density (MVD) and the degree of VEGF expression in these specimens. This was correlated with patient outcome in terms of local recurrence, metastasis and death. Histological results were also compared to a group of patients less than 40 years of age. RESULTS: Of the 11 patients, 9 were male and 2 were female and the mean age was 58 years (range, 42-85). In 7 patients, osteosarcoma arose secondarily from Paget's disease of the bone. The most common site involved was the humerus (7) followed by the femur (2) then pelvis (1) and ulna (1). At the time of diagnosis, 4 patients had metastatic disease. Preoperative chemotherapy was given to 4 patients, with a good response in 3 patients. Six patients underwent limb-sparing surgery, 4 had amputations and 1 was treated with radiotherapy alone. The mean follow up time was 31.5 months (range, 8-81). At this time, 4 patients (36%) had developed lung metastases and 5 patients (46%) had died. Overall survival was 54.5%. Intratumoural MVD was higher in patients over 40 years, although not statistically significant (p = 0.111, CD31; p = 0.134, CD34). VEGF was uniformly expressed in all sections, however no relationship was found between the degree of expression and patient age. CONCLUSION: The prognosis for older patients with osteosarcoma is generally poor. Initial presentation is commonly associated with metastatic disease and neoadjuvant chemotherapy is often avoided because of its side effects. Increased intratumoural vascularity may contribute to the poorer prognosis in these patients, however further studies are needed.
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ItemResearch: Is resection of tumours involving the pelvic ring justified? : A review of 49 consecutive cases.(Springer Science and Business Media LLC, 2005-04-09)INTRODUCTION: Pelvic surgery is challenging and impacts significantly on limb and visceral function, thus, raising the question "is heroic surgery justifiable". This study assessed the functional, oncologic and surgical outcomes following pelvis tumour resections. METHODS: Between 1996-2003, 49 patients (mean age 43 years) underwent pelvic tumour resections- 38 primary malignant tumours, 5 secondary tumours and 6 benign tumours. Bone tumours comprised 5 osteosarcomas, 5 Ewings sarcomas, and 12 chondrosarcomas. Of the soft tumours, 9 were of neural origin. Tumours involved the ilium, acetabulum, pubic bones, sacrum or a combination of these. Functional assessment was performed and no patient had metastases at presentation. RESULTS: There were 41 limb sparing resections and 8 hindquarter amputations. Surgical margins were intralesional (1), marginal (13), wide (26), and radical (3). Of limb sparing surgery, prosthetic reconstructions were performed in 10 patients, biologic reconstructions in 6, a combination of these in 3 and no reconstruction in others. There was 1 intraoperative death, 7 local recurrences and 19 metastases. Death from disease occurred at a mean of 14.2 months with a mean followup of 27 (1-96) months. Amputation and periacetabular resections had worse functional outcomes. Emotional acceptance was surprisingly high. CONCLUSION: Pelvic resections are complex. Functional outcome is significantly affected by surgery. Disease control is similar to limb tumours. Emotional acceptance of surgery in survivors was surprisingly high. Major pelvic resection for malignancy appears justified.
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ItemSafety of rFVIIa in hemodynamically unstable polytrauma patients with traumatic brain injury:: Post hoc analysis of 30 patients from a prospective, randomized, placebo-controlled, double-blind clinical trial(BMC, 2007)BACKGROUND: Trauma is a leading cause of mortality and morbidity, with traumatic brain injury (TBI) and uncontrolled hemorrhage responsible for the majority of these deaths. Recombinant activated factor VIIa (rFVIIa) is being investigated as an adjunctive hemostatic treatment for bleeding refractory to conventional replacement therapy in trauma patients. TBI is a common component of polytrauma injuries. However, the combination of TBI with polytrauma injuries is associated with specific risk factors and treatment modalities somewhat different from those of polytrauma without TBI. Although rFVIIa treatment may offer added potential benefit for patients with combined TBI and polytrauma, its safety in this population has not yet been assessed. We conducted a post hoc sub analysis of patients with TBI and severe blunt polytrauma enrolled into a prospective, international, double-blind, randomized, placebo-controlled study. METHODS: A post hoc analysis of study data was performed for 143 patients with severe blunt trauma enrolled in a prospective, randomized, placebo-controlled study, evaluating the safety and efficacy of intravenous rFVIIa (200 + 100 + 100 microg/kg) or placebo, to identify patients with a computed tomography (CT) diagnosis of TBI. The incidences of ventilator-free days, intensive care unit-free days, and thromboembolic, serious, and adverse events within the 30-day study period were assessed in this cohort. RESULTS: Thirty polytrauma patients (placebo, n = 13; rFVIIa, n = 17) were identified as having TBI on CT. No significant differences in rates of mortality (placebo, n = 6, 46%, 90% confidence interval (CI): 22% to 71%; rFVIIa, n = 5, 29%, 90% CI: 12% to 56%; P = 0.19), in median numbers of intensive care unit-free days (placebo = 0, rFVIIa = 3; P = 0.26) or ventilator-free days (placebo = 0, rFVIIa = 10; P = 0.19), or in rates of thromboembolic adverse events (placebo, 15%, 90% CI: 3% to 51%; rFVIIa, 0%, 90% CI: 0% to 53%; P = 0.18) or serious adverse events (placebo, 92%, 90% CI: 68% to 98%; rFVIIa, 82%, 90% CI: 60% to 92%; P = 0.61) were observed between treatment groups. CONCLUSION: The use of a total dose of 400 (200 + 100 + 100) microg/kg rFVIIa in this group of hemodynamically unstable polytrauma patients with TBI was not associated with an increased risk of mortality or with thromboembolic or adverse events.
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ItemIntraosseous angiosarcoma with secondary aneurysmal bone cysts presenting as an elusive diagnostic challenge.(Springer Science and Business Media LLC, 2008-05-20)Angiosarcoma of bone is an exceedingly rare primary bone malignancy that can present as an aggressive osteolytic lesion. Histological diagnosis can be extremely challenging, as the pathological features often resemble that of aneurysmal bone cysts. We report an interesting and peculiar case of an intraosseous angiosarcoma that presented as a diagnostic dilemma and discuss the relevant radiological and pathologic findings.
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ItemReconstruction after external hemipelvectomy using tibia-hindfoot rotationplasty with calcaneo-sacral fixation.(Springer Science and Business Media LLC, 2008-01-21)BACKGROUND: External hemipelvectomy is associated with high post operative morbidity and a poor functional outcome. We aim to explore a reconstruction technique to improve function and post operative appearance for patients who undergo external hemipelvectomy. CASE PRESENTATION: We present a Case where extensive cancer involvement of pelvis and femur was managed with a novel surgical technique, which involved a calf sparing modified anterior flap hemipelvectomy combined with rotationplasty of the spared calf and fixation of calcaneus to the sacrum, thereby recreating a new thigh stump. CONCLUSION: Tibia-hindfoot rotationplasty result in good functional outcome and appearance for selected patients undergoing external hemipelvectomy with unaffected external iliac and femoral vessels.
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ItemLessons learnt from the painful shoulder; a case series of malignant shoulder girdle tumours misdiagnosed as frozen shoulder.(Springer Science and Business Media LLC, 2005-01-12)Adhesive capsulitis or frozen shoulder is a common condition characterized by shoulder pain and stiffness. In patients in whom conservative measures have failed, more invasive interventions such as arthrographic or arthroscopic distension can be very effective in relieving symptoms and improving range of movement. However, absolute contraindications to these procedures include the presence of neoplasia around the shoulder girdle. We present five cases referred to our institution where the diagnosis of shoulder joint malignancy was delayed, following prolonged, ineffective treatment for frozen shoulder. These cases highlight the importance of careful review of the radiology and the need for reconsideration of the diagnosis in refractory "frozen shoulder".
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ItemOutcome of surgical management of bony metastases to the humerus and shoulder girdle: a retrospective analysis of 93 patients.(Springer Science and Business Media LLC, 2006-03-01)BACKGROUND: Metastatic disease to the shoulder girdle is a challenging problem because of the potential for pain, pathologic fracture and loss of function of that limb. Management of the bone disease centers around palliation, prevention of further complications and the preservation of residual function. A variety of surgical options exist for managing metastatic disease to the shoulder girdle and our experience with over 90 patients is reported. We focus on a preferred technique of combining rigid intramedullary nailing with cementation. METHODS: Patients with metastatic disease to the shoulder girdle were accrued over a 9 year period from 1996 to 2004. 93 patients were identified with 96 operations being performed. The median age was 63 years (range 33 - 89) and 54% were female. The commonest primary tumor to metastasize was breast, and the proximal and midshaft humerus was involved in 84% of cases. The median survival time was 8 months and at last review 82% of patients had died of their disease RESULTS: Operations performed were intramedullary nailing (n = 51), resection with or without prosthetic reconstruction (n = 34) or plate osteosynthesis (n = 9). The site of the metastasis was a guide to the most appropriate operation. Amputations (n = 2) were not done as the primary procedure. Median post operative hospitalization ranged from 3 to 6 days depending on the type of operation performed. Our preferred technique for diaphyseal lesions (intramedullary nailing plus cementation) achieved excellent results in terms of pain relief, functional restoration and minimal complications. Functional restriction was most notable for proximal humeral prostheses (35% of patients). CONCLUSION: Surgical treatment of metastases to the shoulder girdle can be successful, allowing prompt relief of pain and return to prehospital level of care. Proximal and midshaft humeral metastases are easily amenable to resection and reconstruction or intramedullary nailing with cementation. Relief of pain and preservation of function occurs for the majority of patients.
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ItemMultidisciplinary approach to diagnosis and management of osteosarcoma - a review of the St Vincent's Hospital experience.(Springer Science and Business Media LLC, 2006-11-03)BACKGROUND: Osteosarcoma is the most common primary malignant bone tumour in children and young adults. Despite advances in the diagnosis and management of osteosarcoma, there have been few recent studies describing the experiences of tertiary referral centres. This paper aims to describe and discuss the clinical features, pre-operative work-up, management and outcomes of these patients at St Vincent's Hospital (Melbourne, Australia). METHODS: Retrospective study of fifty-nine consecutive patients managed for osteosarcoma at St Vincent's Hospital between 1995 and 2005. RESULTS: Median age at diagnosis was 21 (range, 11-84) years. Gender distribution was similar, with thirty-one male and twenty-eight female patients.Twenty-five patients had osteosarcoma in the femur, eleven each were located in the humerus and tibia, six were identified in the pelvis, and one each in the clavicle, maxilla, fibula, sacrum, ulna and radius.Pre-operative tissue diagnosis of osteosarcoma was obtained through computed tomography-guided percutaneous biopsy in over ninety percent of patients. Following initial therapy, over fifty percent of patients remained relapse-free during the follow-up period, with twelve percent and twenty-seven percent of patients documented as having local and distant disease recurrence, respectively. Of patients with recurrent disease, sixty-two percent remained disease-free following subsequent surgical intervention (most commonly, pulmonary metastatectomy). CONCLUSION: Patient outcomes can be optimised through a multidisciplinary approach in a tertiary referral centre. At St Vincent's Hospital, survival and relapse rates of patients managed for osteosarcoma compare favourably with the published literature.