Surgery (RMH) - Research Publications
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ItemGlutamate weighted imaging contrast in gliomas with 7 Tesla magnetic resonance imaging(ELSEVIER SCI LTD, 2019)INTRODUCTION: Diffuse gliomas are incurable malignancies, which undergo inevitable progression and are associated with seizure in 50-90% of cases. Glutamate has the potential to be an important glioma biomarker of survival and local epileptogenicity if it can be accurately quantified noninvasively. METHODS: We applied the glutamate-weighted imaging method GluCEST (glutamate chemical exchange saturation transfer) and single voxel MRS (magnetic resonance spectroscopy) at 7 Telsa (7 T) to patients with gliomas. GluCEST contrast and MRS metabolite concentrations were quantified within the tumour region and peritumoural rim. Clinical variables of tumour aggressiveness (prior adjuvant therapy and previous radiological progression) and epilepsy (any prior seizures, seizure in last month and drug refractory epilepsy) were correlated with respective glutamate concentrations. Images were separated into post-hoc determined patterns and clinical variables were compared across patterns. RESULTS: Ten adult patients with a histo-molecular (n = 9) or radiological (n = 1) diagnosis of grade II-III diffuse glioma were recruited, 40.3 +/- 12.3 years. Increased tumour GluCEST contrast was associated with prior adjuvant therapy (p = .001), and increased peritumoural GluCEST contrast was associated with both recent seizures (p = .038) and drug refractory epilepsy (p = .029). We distinguished two unique GluCEST contrast patterns with distinct clinical and radiological features. MRS glutamate correlated with GluCEST contrast within the peritumoural voxel (R = 0.89, p = .003) and a positive trend existed in the tumour voxel (R = 0.65, p = .113). CONCLUSION: This study supports the role of glutamate in diffuse glioma biology. It further implicates elevated peritumoural glutamate in epileptogenesis and altered tumour glutamate homeostasis in glioma aggressiveness. Given the ability to non-invasively visualise and quantify glutamate, our findings raise the prospect of 7 T GluCEST selecting patients for individualised therapies directed at the glutamate pathway. Larger studies with prospective follow-up are required.
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ItemRadiomic features of glucose metabolism enable prediction of outcome in mantle cell lymphoma.(Springer Science and Business Media LLC, 2019-12)PURPOSE: To determine whether [18F]FDG PET/CT-derived radiomic features alone or in combination with clinical, laboratory and biological parameters are predictive of 2-year progression-free survival (PFS) in patients with mantle cell lymphoma (MCL), and whether they enable outcome prognostication. METHODS: Included in this retrospective study were 107 treatment-naive MCL patients scheduled to receive CD20 antibody-based immuno(chemo)therapy. Standardized uptake values (SUV), total lesion glycolysis, and 16 co-occurrence matrix radiomic features were extracted from metabolic tumour volumes on pretherapy [18F]FDG PET/CT scans. A multilayer perceptron neural network in combination with logistic regression analyses for feature selection was used for prediction of 2-year PFS. International prognostic indices for MCL (MIPI and MIPI-b) were calculated and combined with the radiomic data. Kaplan-Meier estimates with log-rank tests were used for PFS prognostication. RESULTS: SUVmean (OR 1.272, P = 0.013) and Entropy (heterogeneity of glucose metabolism; OR 1.131, P = 0.027) were significantly predictive of 2-year PFS: median areas under the curve were 0.72 based on the two radiomic features alone, and 0.82 with the addition of clinical/laboratory/biological data. Higher SUVmean in combination with higher Entropy (SUVmean >3.55 and entropy >3.5), reflecting high "metabolic risk", was associated with a poorer prognosis (median PFS 20.3 vs. 39.4 months, HR 2.285, P = 0.005). The best PFS prognostication was achieved using the MIPI-bm (MIPI-b and metabolic risk combined): median PFS 43.2, 38.2 and 20.3 months in the low-risk, intermediate-risk and high-risk groups respectively (P = 0.005). CONCLUSION: In MCL, the [18F]FDG PET/CT-derived radiomic features SUVmean and Entropy may improve prediction of 2-year PFS and PFS prognostication. The best results may be achieved using a combination of metabolic, clinical, laboratory and biological parameters.
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ItemThe effect of surgical approach on early complications of total hip arthoplasty(BMC, 2019-09-03)BACKGROUND: Total hip arthroplasty (THA) is traditionally associated with a low complication rate, with complications such as infection, fracture and dislocation requiring readmission or reoperation. We seek to identify the complication rate among the anterior, direct lateral and posterior surgical approaches. METHODS: We reviewed all THAs performed at the Epworth Healthcare from 1 July 2014 to 30 June 2016. There were 2437 THAs performed by a variety of approaches. No hips were excluded from this study. We surveyed the hospital database and the Australian Orthopaedic Association National Joint Replacement Registry (AOANJRR) to identify those patients who had been readmitted and/or reoperated on. Details collected included age, gender, laterality of the surgery (left/right/bilateral), surgical approach utilised, complications which occurred. RESULTS: There were 29 peri-prosthetic fractures detected (13 anterior, 9 lateral, 7 posterior) and 10 underwent revision of implant, 19 were fixed. The increased rate of revision in the anterior group was statistically significant. There were 14 dislocations (5 anterior, 1 lateral, 8 posterior) of which 8 prostheses were revised. Three cases operated via the anterior approach and 1 by the lateral had early subsidence without fracture, necessitating revision of the femoral prostheses. Operative site infection occurred in 12 cases (2 anterior, 4 lateral, 6 posterior) with 6 requiring revision of implants. CONCLUSION: The complication rates between the 3 main approaches are similar, but individual surgeons should be vigilant for complications unique to their surgical approaches, such as femoral fractures in the anterior approach and dislocations in the posterior approach.
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ItemUtility of Self-Destructing CRISPR/Cas Constructs for Targeted Gene Editing in the Retina(MARY ANN LIEBERT, INC, 2019-11-01)Safe delivery of CRISPR/Cas endonucleases remains one of the major barriers to the widespread application of in vivo genome editing. We previously reported the utility of adeno-associated virus (AAV)-mediated CRISPR/Cas genome editing in the retina; however, with this type of viral delivery system, active endonucleases will remain in the retina for an extended period, making genotoxicity a significant consideration in clinical applications. To address this issue, we have designed a self-destructing "kamikaze" CRISPR/Cas system that disrupts the Cas enzyme itself following expression. Four guide RNAs (sgRNAs) were initially designed to target Streptococcus pyogenes Cas9 (SpCas9) and after in situ validation, the selected sgRNAs were cloned into a dual AAV vector. One construct was used to deliver SpCas9 and the other delivered sgRNAs directed against SpCas9 and the target locus (yellow fluorescent protein [YFP]), in the presence of mCherry. Both constructs were packaged into AAV2 vectors and intravitreally administered in C57BL/6 and Thy1-YFP transgenic mice. After 8 weeks, the expression of SpCas9 and the efficacy of YFP gene disruption were quantified. A reduction of SpCas9 mRNA was found in retinas treated with AAV2-mediated YFP/SpCas9 targeting CRISPR/Cas compared with those treated with YFP targeting CRISPR/Cas alone. We also show that AAV2-mediated delivery of YFP/SpCas9 targeting CRISPR/Cas significantly reduced the number of YFP fluorescent cells among mCherry-expressing cells (∼85.5% reduction compared with LacZ/SpCas9 targeting CRISPR/Cas) in the transfected retina of Thy1-YFP transgenic mice. In conclusion, our data suggest that a self-destructive "kamikaze" CRISPR/Cas system can be used as a robust tool for genome editing in the retina, without compromising on-target efficiency.
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ItemEnd-of-life care in rural general practice: how best to support commitment and meet challenges?(BMC, 2019-06-25)BACKGROUND: Few studies have specifically assessed the scope, nature and challenges of palliative and end-of-life care in rural general practice. These knowledge gaps limit the development of evidence-based policies and services for patients in the last months of life. This study aimed to explore the perspectives of general practitioners (GPs) and other stakeholders on rural GPs' involvement and challenges in providing palliative and end-of-life care in regional Australia. METHODS: A qualitative study involving five focus groups with 26 GPs based in rural/regional Western Australia together with 15 individual telephone interviews with four GPs and 11 other stakeholders involved in end-of-life care across Australia. RESULTS: The rural GPs' central role in end-of-life care was recognized by the majority of participants but multiple challenges were also identified. Some challenges were comparable to those found in urban settings but others were more pronounced, including resource limitations and lack of training. Inappropriate payment models discouraged GPs' involvement in some aspects of end-of-life care, such as case conferences and home visits. Compared to GPs in urban settings, those in rural/regional communities often reported closer doctor-patient relationships and better care integration and collaboration. These positive aspects of care could be further developed to enhance service provision. Our study highlighted the importance of regular interactions with other professionals and patients in providing end-of-life care, but many GPs and other stakeholders found such interactions more challenging than the more "technical" aspects of care. CONCLUSIONS: Rural/regional GPs appear to be disproportionately affected by inappropriate payment models and limited resources, but may benefit from closer doctor-patient relationships and better care integration and collaboration relative to urban GPs. Systematic collection of empirical data on GP management at end-of-life is required to build on these strengths and address the challenges.
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ItemThe distribution and determinants of mammographic density measures in Western Australian aboriginal women(BMC, 2019-02-28)BACKGROUND: Mammographic density (MD) is an established risk factor for breast cancer. There are significant ethnic differences in MD measures which are consistent with those for corresponding breast cancer risk. This is the first study investigating the distribution and determinants of MD measures within Aboriginal women of Western Australia (WA). METHODS: Epidemiological data and mammographic images were obtained from 628 Aboriginal women and 624 age-, year of screen-, and screening location-matched non-Aboriginal women randomly selected from the BreastScreen Western Australia database. Women were cancer free at the time of their mammogram between 1989 and 2014. MD was measured using the Cumulus software. Kolmogorov-Smirnov tests were used to compare distributions of absolute dense area (DA), precent dense area (PDA), non-dense area (NDA) and total breast area between Aboriginal and non-Aboriginal women. General linear regression was used to estimate the determinants of MD, adjusting for age, NDA, hormone therapy use, family history, measures of socio-economic status and remoteness of residence for Aboriginal and non-Aboriginal women separately. RESULTS: Aboriginal women were found to have lower DA and PDA and higher NDA than non-Aboriginal women. Age (p < 0.001) was negatively associated and several socio-economic indices (p < 0.001) were positively associated with DA and PDA in Aboriginal and non-Aboriginal women. Remoteness of residence was associated with both mammographic measures but for non-Aboriginal women only. CONCLUSIONS: Aboriginal women have, on average, less MD than non-Aboriginal women but the factors associated with MD are similar for both sample populations. Since reduced MD is associated with improved sensitivity of mammography, this study suggests that mammographic screening is a particularly good test for Australian Indigenous women, a population that suffers from high breast cancer mortality.
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ItemPatient preferences for adjuvant radiotherapy in early breast cancer are strongly influenced by treatment received through random assignment(WILEY, 2019-03)OBJECTIVE: TARGIT-A randomised women with early breast cancer to receive external beam radiotherapy (EBRT) or intraoperative radiotherapy (TARGIT-IORT). This study aimed to identify what extra risk of recurrence patients would accept for perceived benefits and risks of different radiotherapy treatments. METHODS: Patient preferences were determined by self-rated trade-off questionnaires in two studies: Stage (1) 209 TARGIT-A participants (TARGIT-IORTn = 108, EBRTn = 101); Stage (2) 123 non-trial patients yet to receive radiotherapy (pre-treatment group), with 85 also surveyed post-radiotherapy. Patients traded-off risks of local recurrence in preference selection between TARGIT-IORT and EBRT. RESULTS: TARGIT-IORT patients were more accepting of IORT than EBRT patients with 60% accepting the highest increased risk presented (4%-6%) compared to 12% of EBRT patients, and 2% not accepting IORT at all compared to 43% of EBRT patients. Pre-treatment patients were more accepting of IORT than post-treatment patients with 23% accepting the highest increased risk presented compared to 15% of post-treatment patients, and 15% not accepting IORT at all compared to 41% of pre-treatment patients. CONCLUSIONS: Breast cancer patients yet to receive radiotherapy accept a higher recurrence risk than the actual risk found in TARGIT-A. Measured patient preferences are highly influenced by experience of treatment received. This finding challenges the validity of post-treatment preference studies.
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ItemPromoting physical activity in regional and remote cancer survivors (PPARCS) using wearables and health coaching: randomised controlled trial protocol(BMJ PUBLISHING GROUP, 2019-05)INTRODUCTION: Physically active cancer survivors have substantially less cancer recurrence and improved survival compared with those who are inactive. However, the majority of survivors (70%-90%) are not meeting the physical activity (PA) guidelines. There are also significant geographic inequalities in cancer survival with poorer survival rates for the third of Australians who live in non-metropolitan areas compared with those living in major cities. The primary objective of the trial is to increase moderate-to-vigorous PA (MVPA) among cancer survivors living in regional and remote Western Australia. Secondary objectives are to reduce sedentary behaviour and in conjunction with increased PA, improve quality of life (QoL) in non-metropolitan survivors. Tertiary objectives are to assess the effectiveness of the health action process approach (HAPA) model variables, on which the intervention is based, to predict change in MVPA. METHODS AND ANALYSIS: Eighty-six cancer survivors will be randomised into either the intervention or control group. Intervention group participants will receive a Fitbit and up to six telephone health-coaching sessions. MVPA (using Actigraph), QoL and psychological variables (based on the HAPA model via questionnaire) will be assessed at baseline, 12 weeks (end of intervention) and 24 weeks (end of follow-up). A general linear mixed model will be used to assess the effectiveness of the intervention. ETHICS AND DISSEMINATION: Ethics approval has been obtained from St John of God Hospital Subiaco (HREC/#1201). We plan to submit a manuscript of the results to a peer-reviewed journal. Results will be presented at conferences, community and consumer forums and hospital research conferences. TRIAL REGISTRATION NUMBER: ACTRN12618001743257; pre-results, U1111-1222-5698.
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ItemQuality of handwritten surgical operative notes from surgical trainees: a noteworthy issue(WILEY, 2019-03)BACKGROUND: Surgical operation notes are crucial for medical record keeping and information flow in continued patient care. In addition to inherent medical implications, the quality of operative notes also has important economic and medico-legal ramifications. Further, well-documented records can also be useful for audit purposes and propagation of research, facilitating the improvement of delivery of care to patients. We aimed to assess the quality of surgical operation notes written by junior doctors and trainees against a set standard, to ascertain whether these standards were met. METHOD: We undertook an audit of Urology and General Surgery operation notes handwritten by junior doctors and surgical trainees in a tertiary teaching hospital over a month period both in 2014 and 2015. Individual operative notes were assessed for quality based on parameters described by the Royal College of Surgeons of England guidelines. RESULTS: Based on the Royal College of Surgeons of England guidelines, a significant proportion of analysed surgical operative notes were incomplete, with information pertaining to the time of surgery, name of anaesthetist and deep vein thrombosis prophylaxis in particular being recorded less than 50% of the time (22.42, 36.36 and 43.03%, respectively).Overall, 80% compliance was achieved in 14/20 standards and 100% compliance was attained in only one standard. CONCLUSIONS: The quality of surgical operation notes written by junior doctors and trainees demonstrated significant deficiencies when compared against a set standard. There is a clear need to educate junior medical staff and to provide systems and ongoing education to improve quality. This would involve leadership from senior staff, ongoing audit and the development of systems that are part of the normal workflow to improve quality and compliance.
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