Surgery (St Vincent's) - Research Publications
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ItemNo Preview AvailableThe relevance of ligament balancing in total knee arthroplasty: how important is it? A systematic review of the literature(PAGEPRESS PUBL, 2009)Ligament balancing affects many of the postoperative criteria for a successful knee replacement. A balanced knee contributes to improved alignment and stability. Ligament balancing helps reduce wear and loosening of the joint. A patient with a balanced knee is more likely to have increased range of motion and proprioception, and decreased pain. All these factors help minimize the need for revision surgery. Complications associated with ligament balancing can include instability caused by over-balancing and the possibility of neurovascular damage during or as a result of ligament balancing. This article attempts to summarize the literature, to define a balanced knee, and outline the benefits and possible complications of ligament balancing. Different techniques, sequences, and tools used in ligament balancing, and their relevance in correcting various deformities are reviewed.
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ItemThe impact of 18-fluorodeoxyglucose positron emission tomography on the staging, management and outcome of anal cancer(NATURE PUBLISHING GROUP, 2009-03-03)Accurate inguinal and pelvic nodal staging in anal cancer is important for the prognosis and planning of radiation fields. There is evidence for the role of 18-fluorodeoxyglucose positron emission tomography (FDG-PET) in the staging and management of cancer, with early reports of an increasing role in outcome prognostication in a number of tumours. We aimed to determine the effect of FDG-PET on the nodal staging, radiotherapy planning and prognostication of patients with primary anal cancer. Sixty-one consecutive patients with anal cancer who were referred to a tertiary centre between August 1997 and November 2005 were staged with conventional imaging (CIm) (including computed tomography (CT), magnetic resonance imaging, endoscopic ultrasound and chest X-ray) and by FDG-PET. The stage determined by CIm and the proposed management plan were prospectively recorded and changes in stage and management as a result of FDG-PET assessed. Patients were treated with a uniform radiotherapy technique and dose. The accuracy of changes and prognostication of FDG-PET were validated by subsequent clinical follow-up. Kaplan-Meier survival analysis was used to estimate survival for the whole cohort and by FDG-PET and CIm stage. The tumour-stage group was changed in 23% (14 out of 61) as a result of FDG-PET (15% up-staged, 8% down-staged). Fourteen percent of T1 patients (3 out of 22), 42% of T2 patients (10 out of 24) and 40% of T3-4 patients (6 out of 15) assessed using CIm, had a change in their nodal or metastatic stage following FDG-PET. Sensitivity for nodal regional disease by FDG-PET and CIm was 89% and 62%, respectively. The staging FDG-PET scan altered management intent in 3% (2 out of 61) and radiotherapy fields in 13% (8 out of 61). The estimated 5-year overall survival (OS) and progression-free survival (PFS) for the cohort were 77.3% (95% confidence interval (CI): 55.3-90.4%) and 72.2% (95% CI: 51.5-86.4%), respectively. The estimated 5-year PFS for FDG-PET and CIm staged N2-3 disease was 70% (95% CI: 42.8-87.9%) and 55.3% (95% CI: 23.3-83.4%), respectively. FDG-PET shows increased sensitivity over CIm for staging nodal disease in anal cancer and changes treatment intent or radiotherapy prescription in a significant proportion of patients.
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ItemMyoepithelioma within the carpal tunnel: a case report and review of the literature.(Springer Science and Business Media LLC, 2009-09-09)Myoepitheliomas of the extremity are rare and usually benign, while a minority display malignant features. This case demonstrates the diagnosis and management of myoepithelioma within the carpal tunnel. Clinical and radiological tumour features were evaluated. Hematoxylin and eosin stained tumour sections were examined, and immunohistochemistry was performed. Histology revealed a nodular mass of epithelioid cells in clusters within a myxoid/chondroid stroma. No mitoses were noted. Cytokeratins, neuron-specific enolase, synaptophysin, glial fibrillary acidic protein, and S100 were positive on immunohistochemistry. A literature review revealed very few prior reports of myoepithelioma in the wrist, and limited data concerning any relationship between recurrence and quality of surgical margins. In this case, wide local excision would have significantly compromised dominant hand function, and therefore a marginal excision was deemed appropriate in the context of bland histological features. Surgical margins noted in future case reports will aid clinical decision making.
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ItemResident macrophages influence stem cell activity in the mammary gland(BMC, 2009)INTRODUCTION: Macrophages in the mammary gland are essential for morphogenesis of the ductal epithelial tree and have been implicated in promoting breast tumor metastasis. Although it is well established that macrophages influence normal mammopoiesis, the mammary cell types that these accessory cells influence have not been determined. Here we have explored a role for macrophages in regulating mammary stem cell (MaSC) activity, by assessing the ability of MaSCs to reconstitute a mammary gland in a macrophage-depleted fat pad. METHODS: Two different in vivo models were used to deplete macrophages from the mouse mammary fat pad, allowing us to examine the effect of macrophage deficiency on the mammary repopulating activity of MaSCs. Both the Csf1op/op mice and clodronate liposome-mediated ablation models entailed transplantation studies using the MaSC-enriched population. RESULTS: We show that mammary repopulating ability is severely compromised when the wild-type MaSC-enriched subpopulation is transplanted into Csf1op/op fat pads. In reciprocal experiments, the MaSC-enriched subpopulation from Csf1op/op glands had reduced regenerative capacity in a wild-type environment. Utilizing an alternative strategy for selective depletion of macrophages from the mammary gland, we demonstrate that co-implantation of the MaSC-enriched subpopulation with clodronate-liposomes leads to a marked decrease in repopulating frequency and outgrowth potential. CONCLUSIONS: Our data reveal a key role for mammary gland macrophages in supporting stem/progenitor cell function and suggest that MaSCs require macrophage-derived factors to be fully functional. Macrophages may therefore constitute part of the mammary stem cell niche.
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ItemAn interesting diagnosis for a presacral mass: case report.(Springer Science and Business Media LLC, 2009-11-08)A presacral mass can present a diagnostic dilemma for the surgical oncologist. Differential diagnoses include congenital causes such as teratoma or chordoma, neurological causes such as neurilemoma or neurofibroma or other malignancies such as lymphoma or sarcoma. Diagnosis usually requires imaging such as CT and MRI and tissue biopsy. We present an unusual cause of a presacral mass being extramedullary haematopoiesis, found incidentally in a 71 year old female. Extramedullary haematopoiesis is defined as the production of myeloid and erythroid elements outside of the bone-marrow. This diagnosis is extremely rare in the presacral area especially in a patient with no haematological abnormalities. A review of the literature is presented.
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ItemDevelopment and evaluation of a tool for the assessment of footwear characteristics(BMC, 2009)BACKGROUND: Footwear characteristics have been linked to falls in older adults and children, and the development of many musculoskeletal conditions. Due to the relationship between footwear and pathology, health professionals have a responsibility to consider footwear characteristics in the etiology and treatment of various patient presentations. In order for health professionals and researchers to accurately and efficiently critique an individual's footwear, a valid and reliable footwear assessment tool is required. The aim of this study was to develop a simple, efficient, and reliable footwear assessment tool potentially suitable for use in a range of patient populations. METHODS: Consideration of previously published tools, other footwear related literature, and clinical considerations of three therapists were used to assist in the development of the tool. The tool was developed to cover fit, general features, general structure, motion control properties, cushioning, and wear patterns. A total of 15 participants (who provided two pairs of shoes each) were recruited, and assessment using the scale was completed on two separate occasions (separated by 1 - 3 weeks) by a physiotherapist and a podiatrist on each participant's dominant foot. Intra-rater and inter-rater reliability were evaluated using intra-class correlation coefficients (ICCs) (model 2, 1) and the 95% limits of agreement (95% LOAs) for continuous items, and percentage agreement and kappa (kappa) statistics for categorical items. RESULTS: All categorical items demonstrated high percentage agreement statistic for intra-rater (83 - 100%) and inter-rater (83 - 100%) comparisons. With the exception of last shape and objective measures used to categorise the adequacy of length, excellent intra-rater (ICC = 0.91 - 1.00) and inter-rater reliability (ICC = 0.90 - 1.00) was indicated for continuous items in the tool, including the motion control properties scale (0.91 - 0.95). CONCLUSION: A comprehensive footwear assessment tool with good face validity has been developed to assist future research and clinical footwear assessment. Generally good reliability amongst all items indicates that the tool can be used with confidence in research and clinical settings. Further research is now required to determine the clinical validity of each item in various patient populations.
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ItemIdentification of circulating tumour cells in early stage breast cancer patients using multi marker immunobead RT-PCR(BIOMED CENTRAL LTD, 2009-06-05)INTRODUCTION: The ability to screen blood of early stage operable breast cancer patients for circulating tumour cells is of potential importance for identifying patients at risk of developing distant relapse. We present the results of a study of the efficacy of the immunobead RT-PCR method in identifying patients with circulating tumour cells. RESULTS: Immunomagnetic enrichment of circulating tumour cells followed by RT-PCR (immunobead RT-PCR) with a panel of five epithelial specific markers (ELF3, EPHB4, EGFR, MGB1 and TACSTD1) was used to screen for circulating tumour cells in the peripheral blood of 56 breast cancer patients. Twenty patients were positive for two or more RT-PCR markers, including seven patients who were node negative by conventional techniques. Significant increases in the frequency of marker positivity was seen in lymph node positive patients, in patients with high grade tumours and in patients with lymphovascular invasion. A strong trend towards improved disease free survival was seen for marker negative patients although it did not reach significance (p = 0.08). CONCLUSION: Multi-marker immunobead RT-PCR analysis of peripheral blood is a robust assay that is capable of detecting circulating tumour cells in early stage breast cancer patients.
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ItemStaurosporine augments EGF-mediated EMT in PMC42-LA cells through actin depolymerisation, focal contact size reduction and Snail1 induction - A model for cross-modulation(BMC, 2009-07-15)BACKGROUND: A feature of epithelial to mesenchymal transition (EMT) relevant to tumour dissemination is the reorganization of actin cytoskeleton/focal contacts, influencing cellular ECM adherence and motility. This is coupled with the transcriptional repression of E-cadherin, often mediated by Snail1, Snail2 and Zeb1/deltaEF1. These genes, overexpressed in breast carcinomas, are known targets of growth factor-initiated pathways, however it is less clear how alterations in ECM attachment cross-modulate to regulate these pathways. EGF induces EMT in the breast cancer cell line PMC42-LA and the kinase inhibitor staurosporine (ST) induces EMT in embryonic neural epithelial cells, with F-actin de-bundling and disruption of cell-cell adhesion, via inhibition of aPKC. METHODS: PMC42-LA cells were treated for 72 h with 10 ng/ml EGF, 40 nM ST, or both, and assessed for expression of E-cadherin repressor genes (Snail1, Snail2, Zeb1/deltaEF1) and EMT-related genes by QRT-PCR, multiplex tandem PCR (MT-PCR) and immunofluorescence +/- cycloheximide. Actin and focal contacts (paxillin) were visualized by confocal microscopy. A public database of human breast cancers was assessed for expression of Snail1 and Snail2 in relation to outcome. RESULTS: When PMC42-LA were treated with EGF, Snail2 was the principal E-cadherin repressor induced. With ST or ST+EGF this shifted to Snail1, with more extreme EMT and Zeb1/deltaEF1 induction seen with ST+EGF. ST reduced stress fibres and focal contact size rapidly and independently of gene transcription. Gene expression analysis by MT-PCR indicated that ST repressed many genes which were induced by EGF (EGFR, CAV1, CTGF, CYR61, CD44, S100A4) and induced genes which alter the actin cytoskeleton (NLF1, NLF2, EPHB4). Examination of the public database of breast cancers revealed tumours exhibiting higher Snail1 expression have an increased risk of disease-recurrence. This was not seen for Snail2, and Zeb1/deltaEF1 showed a reverse correlation with lower expression values being predictive of increased risk. CONCLUSION: ST in combination with EGF directed a greater EMT via actin depolymerisation and focal contact size reduction, resulting in a loosening of cell-ECM attachment along with Snail1-Zeb1/deltaEF1 induction. This appeared fundamentally different to the EGF-induced EMT, highlighting the multiple pathways which can regulate EMT. Our findings add support for a functional role for Snail1 in invasive breast cancer.
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ItemKeratan sulphate in the interglobular domain has a microstructure that is distinct from keratan sulphate elsewhere on pig aggrecan(ELSEVIER SCIENCE BV, 2009-01)The microstructure of keratan sulphate purified from the interglobular domain, the keratan sulphate-rich region and total aggrecan was compared using fluorophore-assisted-carbohydrate-electrophoresis. Keratan sulphate in the interglobular domain was substantially less sulphated than keratan sulphate elsewhere on aggrecan, based on the ratio of unsulphated: monosulphated disaccharides generated by endo-beta-galactosidase digestion, and the ratio of monosulphated: disulphated disaccharides generated by keratanase II digestion. The ratio of unsulphated: monosulphated: disulphated disaccharides was 1:4:5 for keratan sulphate from total aggrecan and the keratan sulphate-rich region, but only 1:0.9:0.8 for the interglobular domain. These results show that keratan sulphate in the interglobular domain of pig aggrecan has a microstructure that is distinct from keratan sulphate in the keratan sulphate-rich region.