Sir Charles Gairdner Hospital Research Articles

Percutaneous microwave ablation of T1a renal cell carcinomas: A 10-year single-center retrospective review.

Partial nephrectomy is currently the preferred treatment option for T1a renal cell carcinomas (RCC), with nephron-sparing techniques, including microwave ablation, becoming more common in select patients. Primary aims are to document outcomes of microwave ablation for T1a RCCs in an Australian tertiary centre to add to the evidence for its safety and efficacy. The prospectively maintained Sir Charles Gairdner Hospital Interventional Radiology database was retrospectively searched for all Renal Microwave ablations completed between June 2012 and February 2022. This database and a combination of hospital programmes including Agfa Impax PACS, Bossnet digital medical record and iSoft Clinical Manager were used to extract the relevant data which was anonymized and entered into an Excel spreadsheet for analysis. Forty-eight patients underwent microwave ablation for 50 tumours. Of these, there were two local and two distant recurrences. A fifth patient had metastases on presentation. Higher local recurrence rates were associated with larger tumour size (P = 0.043). Tumour proximity to the collecting system <4 mm was associated with higher rates of complications (P = 0.020). RENAL scores did not show statistically significant correlation with complications (P = 0.092) or local or distant recurrence. Notably, the study follow-up time was longer than many comparative studies (mean = 2796, ~7.66 years censoring for death and mean = 832 days, ~2.28 years not censoring for death). Consistent with the literature, this study further demonstrates that microwave ablation is a safe and efficacious option for treatment of T1a RCC.

Sutton-Kadir Syndrome can be treated safely with endovascular embolisation alone.

Sutton-Kadir Syndrome (SKS) describes true inferior pancreaticoduodenal artery (IPDA) aneurysms in the setting of coeliac artery (CA) stenosis or occlusion. Although rare, SKS aneurysms can rupture and cause morbidity. Due to its rarity and lack of controlled treatment data, correct treatment for the CA lesion is currently unknown. Our aim was to assess if endovascular embolisation alone was safe and effective in treatment of SKS aneurysms, in emergent and elective settings. Secondary objectives were to describe presentation and imaging findings. A retrospective cohort study of patients treated at Sir Charles Gairdner Hospital between January 2014 and December 2021 was done. Data on presentation, diagnostics, aneurysm characteristics, CA lesion aetiology, treatment and outcomes were extracted from chart review. Twenty-four aneurysms in 14 patients were identified. Rupture was seen in 7/15 patients. Most aneurysms (22/24) were in the IPDA or one of its anterior or posterior branches. Median arcuate ligament (MAL) compression was identified in all. There was no difference in median (IQR) maximal transverse diameter between ruptured and non-ruptured aneurysms (6 mm (9), 12 mm (6), P = 0.18). Of ruptures, 6/7 had successful endovascular embolisation and 1/7 open surgical ligation. Of non-ruptures, 6/7 had successful endovascular embolisation, 1/7 open MAL division then endovascular CA stenting and aneurysm embolisation. No recurrences or new aneurysms were detected with computed tomography or magnetic resonance angiography over a median (IQR) follow-up period of 30 (10) months in 12 patients. Endovascular embolisation of SKS aneurysms without treatment of MAL compression is safe and effective in both the emergent and elective settings.

Navigating the 2021 ACPSEM ROMP workforce model: insights from a single institution.

Workforce modelling for Radiation Oncology Medical Physicists (ROMPs) is evolving and challenging, prompting the development of the 2021 Australasian College of Physical Scientists and Engineers in Medicine (ACPSEM) ROMP Workforce (ARW) Model. In the exploration of this model at Sir Charles Gairdner Hospital, a comprehensive productivity exercise was conducted to obtain a detailed breakdown of ROMP time at a granular level. The results provide valuable insights into ROMP activities and enabled an evaluation of ARW Model calculations. The findings also capture the changing ROMP role as evidenced by an increasing involvement in consultation and advisory tasks with other professionals in the field. They also suggest that CyberKnife QA time requirements in the data utilised by the model may need to be revised. This study emphasises features inherent in the model, that need to be understood if the model is to be applied correctly.

Machine learning pipeline for blood culture outcome prediction using Sysmex XN-2000 blood sample results in Western Australia

BackgroundBloodstream infections (BSIs) are a significant burden on the global population and represent a key area of focus in the hospital environment. Blood culture (BC) testing is the standard diagnostic test utilised to confirm the presence of a BSI. However, current BC testing practices result in low positive yields and overuse of the diagnostic test. Diagnostic stewardship research regarding BC testing is increasing, and becoming more important to reduce unnecessary resource expenditure and antimicrobial use, especially as antimicrobial resistance continues to rise. This study aims to establish a machine learning (ML) pipeline for BC outcome prediction using data obtained from routinely analysed blood samples, including complete blood count (CBC), white blood cell differential (DIFF), and cell population data (CPD) produced by Sysmex XN-2000 analysers.MethodsML models were trained using retrospective data produced between 2018 and 2019, from patients at Sir Charles Gairdner hospital, Nedlands, Western Australia, and processed at Pathwest Laboratory Medicine, Nedlands. Trained ML models were evaluated using stratified 10-fold cross validation.ResultsTwo ML models, an XGBoost model using CBC/DIFF/CPD features with boruta feature selection (BFS) , and a random forest model trained using CBC/DIFF features with BFS were selected for further validation after obtaining AUC scores of 0.76 pm 0.04 and 0.75 pm 0.04 respectively using stratified 10-fold cross validation. The XGBoost model obtained an AUC score of 0.76 on a internal validation set. The random forest model obtained AUC scores of 0.82 and 0.76 on internal and external validation datasets respectively.ConclusionsWe have demonstrated the utility of using an ML pipeline combined with CBC/DIFF, and CBC/DIFF/CPD feature spaces for BC outcome prediction. This builds on the growing body of research in the area of BC outcome prediction, and provides opportunity for further research.

Resection of Retroperitoneal Sarcomas Involving the Inferior Vena Cava With the Use of Veno-Veno Extracorporeal Perfusion: A Review of the First 20 Cases Performed at Sir Charles Gairdner Hospital, Perth, West Australia

Prolonged inferior vena cava (IVC) clamping during retroperitoneal sarcoma resection presents specific challenges requiring a multidisciplinary approach. Veno-veno bypass (VVB) drains blood from the IVC and returns it into the right atrium, allowing excellent surgical exposure. This institution has routinely used VVB for sarcoma resections involving the IVC since 2018. This review describes outcomes of the first 20 cases.

Getting into shape: the tongue and hypoglossal nerve stimulation.

Subscription RequiredCommentaryGetting into shape: the tongue and hypoglossal nerve stimulation David R. Hillman, MBBS David R. Hillman, MBBS Centre for Sleep Science, School of Human Sciences, The University of Western Australia, Perth, Western Australia, Australia West Australian Sleep Disorders Research Institute, Sir Charles Gairdner Hospital, Perth, Western Australia, Australia Search for more papers by this author Published Online:March 1, 2023https://doi.org/10.5664/jcsm.10550

Cost analysis of a watch-and-wait approach in patients with a complete clinical response to chemoradiotherapy for rectal cancer.

There is increasing interest in the watch-and-wait approach for patients with rectal cancer who have had a complete clinical response following neoadjuvant long course chemoradiotherapy. This study is a cost analysis of expenditure on patients in the watch-and-wait program versus patients who underwent standard rectal resection followed by routine surveillance. Data were prospectively collated and retrospectively analysed in all patients who presented with rectal cancer from January 2016 to January 2018 at Sir Charles Gairdner Hospital, Perth, Western Australia. Software developed by the North Metropolitan Health Service was used to capture comprehensive data to calculate the in-hospital expenditure for an individual patient throughout their treatment journey. For a patient enrolled in the watch-and-wait pathway, the total cost of surveillance over a 5-year period was $45 246. This was compared with the cost of an ultra-low anterior resection/loop ileostomy/closure of loop and routine postoperative surveillance which came to a total of $87 473. While a patient who had an abdominoperineal resection followed by routine 5-year surveillance had an expenditure of $82 290. There is growing evidence that the watch-and-wait strategy is a valid management option. In the cost-conscious environment of the current health care system, the watch-and-wait pathway is a cost-effective and economically advantage treatment.

Fracture liaison service utilising an emergency department information system to identify patients effectively reduce re-fracture rate is cost-effective and cost saving in Western Australia.

ObjectivesTo assess the benefits of the Emergency Department Information System (EDIS)‐linked fracture liaison service (FLS).MethodsPatients identified through EDIS were invited to attend an FLS at the intervention hospital, the Sir Charles Gairdner Hospital (SCGS‐FLS). The intervention group was compared to usual care. Retrospective control (RC) at this hospital determined historical fracture risk (SCGH‐RC). Prospective control (PC) was from a comparator, Fremantle Hospital (FH‐PC). The main outcome measures were cost‐effectiveness from a health system perspective and quality of life by EuroQOL (EQ‐5D). Bottom‐up cost of medical care, against the cost of managing recurrent fracture (weighted basket), was determined from the literature and 2013/14 Australian Refined Diagnosis Related Groups (AR‐DRG) prices. Mean incremental cost‐effectiveness ratios were simulated from 5000 bootstrap iterations. Cost‐effectiveness acceptability curves were generated.ResultsThe SCGH‐FLS program reduced absolute re‐fracture rates versus control cohorts (9.2–10.2%), producing an estimated cost saving of AUD$750,168–AUD$810,400 per 1000 patient‐years in the first year. Between‐groups QALYs differed with worse outcomes in both control groups (p < 0.001).The SCGH‐FLS compared with SCGH‐RC and FH‐PC had a mean incremental cost of $8721 (95% CI −$1218, $35,044) and $8974 (95% CI −$26,701, $69,929), respectively, per 1% reduction in 12‐month recurrent fracture risk. The SCGH‐FLS compared with SCGH‐RC and FH‐PC had a mean incremental cost of $292 (95% CI −$3588, $3380) and −$261 (95% CI −$1521, $471) per EQ‐5D QALY gained at 12 months respectively. With societal willingness to pay of $16,000, recurrent fracture is reduced by 1% in >80% of patients.ConclusionsThis simple and easy model of identification and intervention demonstrated efficacy in reducing rates of recurrent fracture and was cost‐effective and potentially cost saving.

Developing PHarmacie-R: A bedside risk prediction tool with a medicines management focus to identify risk of hospital readmission.

The imperative to identify patients at risk of medication-related harm has never been greater. Hospital clinicians cannot easily predict risk of readmission or harm. Candidate variables associated with medication-related harm derived from the literature or significantly represented in a complex patient cohort have been previously described by PHarmacie-4. With a focus on polypharmacy and high-risk medicines in vulnerable patient cohorts, PHarmacie-4 was easy to use and highlighted risks. However it over-estimated risk, reducing its usefulness in stratifying risk of readmission. Develop a risk prediction tool built into a smart phone app, enabling clinicians to identify and refer high-risk patients for an early post-discharge medicines review. Demonstrate usability, real world application and validity in an independent dataset. A retrospective, observational study was conducted with 1201 randomly selected patients admitted to Sir Charles Gairdner Hospital between June 1, 2016 to December 31, 2016. Patient characteristics and outcomes of interest were reported, including unplanned hospital utilisation at 30, 60 and 90 days post-discharge. Using multivariable logistic regression modelling, an algorithm was developed, built into a smart phone app and used and validated in an independent dataset. 738 patients (61%) were included in the derivation sample. The best predictive performance was achieved by PHarmacie-R (C-statistic 0.72, 95% CI 0.68-0.75) which included PHarmacie-4 risk variables, a non-linear effect of age, unplanned hospital utilisation in the preceding six months and gender. The independent validation dataset had a C-statistic of 0.64 (95% CI 0.56-0.72). PHarmacie-R is the first readmission risk prediction tool, built into a smart phone app, focussing on polypharmacy and high-risk medicines in vulnerable patients. It can assist clinical pharmacists to identify medical inpatients who may benefit from early post-discharge medication management services. External validation is needed to enable application in other clinical settings.

Abdominal aortic calcification on lateral spine images captured during bone density testing and late-life dementia risk in older women: A prospective cohort study

SummaryBackgroundDementia after the age of 80 years (late-life) is increasingly common due to vascular and non-vascular risk factors. Identifying individuals at higher risk of late-life dementia remains a global priority.MethodsIn prospective study of 958 ambulant community-dwelling older women (≥70 years), lateral spine images (LSI) captured in 1998 (baseline) from a bone density machine were used to assess abdominal aortic calcification (AAC). AAC was classified into established categories (low, moderate and extensive). Cardiovascular risk factors and apolipoprotein E (APOE) genotyping were evaluated. Incident 14.5-year late-life dementia was identified from linked hospital and mortality records.FindingsAt baseline women were 75.0 ± 2.6 years, 44.7% had low AAC, 36.4% had moderate AAC and 18.9% had extensive AAC. Over 14.5- years, 150 (15.7%) women had a late-life dementia hospitalisation (n = 132) and/or death (n = 58). Compared to those with low AAC, women with moderate and extensive AAC were more likely to suffer late-life dementia hospitalisations (9.3%, 15.5%, 18.3%, respectively) and deaths (2.8%, 8.3%, 9.4%, respectively). After adjustment for cardiovascular risk factors and APOE, women with moderate and extensive AAC had twice the relative hazards of late-life dementia (moderate, aHR 2.03 95%CI 1.38–2.97; extensive, aHR 2.10 95%CI 1.33–3.32), compared to women with low AAC.InterpretationIn community-dwelling older women, those with more advanced AAC had higher risk of late-life dementia, independent of cardiovascular risk factors and APOE genotype. Given the widespread use of bone density testing, simultaneously capturing AAC information may be a novel, non-invasive, scalable approach to identify older women at risk of late-life dementia.FundingKidney Health Australia, Healthway Health Promotion Foundation of Western Australia, Sir Charles Gairdner Hospital Research Advisory Committee Grant, National Health and Medical Research Council of Australia.

66 Prognostic and predictive value of pre-treatment T-cell receptors (TCR) repertoire in non-small cell lung cancer (NSCLC) patients treated with single agent immunotherapy

BackgroundTCR repertoire plays a key role on the orchestration of the immune response. In particular, reduced pre-treatment Shannon diversity, increase clonality and increase convergence of TCRs have been suggested to reflect clonal expansion of antigen-specific T-cells in the tumour microenvironment. These are thought to be correlated with better response rate, improved progression free survival (PFS) and overall survival (OS). Here we aim to explore the above TCR repertoire features in peripheral blood of NSCLC patients (with PDL1≥50%) treated with single agent pembrolizumab in the first line setting; and correlate them with overall response rate (ORR), PFS and OS.MethodsWe prospectively collected baseline blood from 48 NSCLC patients treated with first line pembrolizumab. High quality DNA was extracted from white blood cells and used for TCR sequencing using the Oncomine TCR Beta-SR Assay (Thermo Fisher). TCR clonality and convergence were calculated for each individual and correlated with survival using Kaplan-Meier curves and survival statistics. Multivariate analysis was carried out controlling for other variable that may influence the association of TCR repertoire and outcomes such as age, sex, ECOG, smoking status and pre-treatment neutrophil to lymphocyte ratio (NLR).ResultsOur data matured for 29 patients only with a follow-up of at least 6 months. We observed a trend towards increased pre-treatment TCR clonality in patients with objective response to pembrolizumab and statistically significant reduced Shannon diversity (P = 0.042). Convergence did not seem to affect ORR in our cohort. Moreover, there was a significantly longer PFS in patients with reduced number of pre-treatment clones (HR = 0.40, 95%CI 0.14–1.17, P = 0.031), reduced Shannon diversity (HR = 0.44, 95%CI 0.16–1.21, P = 0.041), reduced Evenness (HR = 0.31, 95%CI 0.11–0.94, P = 0.033) and elevated clonality (HR = 3.18, 95%CI 1.06–9.53, P = 0.033) (table 1). Reduced rather than increased convergence was correlated with a trend towards improved PFS. None of these parameters were statically significant in relation to OS (table 2).Abstract 66 Table 1TCR diversity and PFSAbstract 66 Table 2TCR diversity and OSConclusionsIncreased pre-treatment TCR clonality and reduced diversity are associated with improved ORR and PFS, but not OS in NSCLC patients with high PD-L1 treated with pembrolizumab monotherapy. Further maturation of this cohort will demonstrate whether the circulating pre-treatment TCR repertoire is a prognostic factor for immunecheckpoint inhibition.Ethics ApprovalThe proposed project has already received approval by the Human Research Ethics Committees and Research Governance at Fiona Stanley Hospital, Sir Charles Gairdner Hospital and Edith Cowan University [ECU (No. 18957) and SCGH (RGS0000003289)].ConsentWritten informed consent was obtained from the patient for publication of this abstract and any accompanying images. A copy of the written consent is available for review by the Editor of this journal.

Serum Fibrosis Tests Guide Prognosis in Metabolic Dysfunction–Associated Fatty Liver Disease Patients Referred From Primary Care

Metabolic dysfunction-associated fatty liver disease (MAFLD) is managed predominately in primary care, however, there is uncertainty regarding how to best identify patients for specialist referral. We examined the accuracy of noninvasive tests as screening tools for the prediction of outcomes in MAFLD patients referred from primary care. Patients with MAFLD referred by primary care for specialist review to Sir Charles Gairdner Hospital (cohort 1, n= 626) or tertiary centers within Western Australia (cohort 2, n= 246) were examined. Hepascore, aspartate aminotransferase to platelet ratio, Fibrosis-4 (FIB-4), and nonalcoholic fatty liver disease fibrosis score performed at baseline were examined for their accuracy in predicting liver-related death (LRD), decompensation, and hepatocellular carcinoma. Outcomes were collected from hospital records and data linkage. The median follow-up period was 5.0 years (range, 0.1-13.0 y) and 3.8 years (range, 0.1-10.0 y) in cohorts 1 and 2, respectively. In both cohorts, Hepascore and FIB-4 had the highest area under the curve for the prediction of LRD (0.90-0.95 and 0.83-0.94, respectively), decompensation (0.86-0.91 and 0.86-0.87, respectively), and hepatocellular carcinoma (0.75-0.90 and 0.67-0.85, respectively). The sensitivity and negative predictive values were high (>90%) for Hepascore (cut-off value, 0.60), FIB-4 (cut-off value, 1.30), and nonalcoholic fatty liver disease fibrosis score (cut-off value, -1.455) for all outcomes in cohort 1, and for predicting LRD in cohort 2. Hepascore had the highest specificity, classified the greatest proportion of patients as low risk, and was favored by decision curve analysis as providing the greatest net benefit. Serum noninvasive tests accurately stratify risk of liver-related outcomes in MAFLD patients and can be used as a screening tool for patients referred for specialist review by primary care.

Impact of Immunohistochemistry-Defined Cell of Origin and MYC Rearrangements on Outcomes in Patients with PET-Defined Stage I/II Diffuse Large B-Cell Lymphoma Treated with R-CHOP ± Radiotherapy: An International Multi-Center Retrospective Study

Impact of Immunohistochemistry-Defined Cell of Origin and MYC Rearrangements on Outcomes in Patients with PET-Defined Stage I/II Diffuse Large B-Cell Lymphoma Treated with R-CHOP ± Radiotherapy: An International Multi-Center Retrospective Study

Feasibility and efficacy of a multicomponent exercise medicine programme in patients with pancreatic cancer undergoing neoadjuvant therapy (the EXPAN trial): study protocol of a dual-centre, two-armed phase I randomised controlled trial

IntroductionExercise is emerging as a therapy in oncology for its physical and psychosocial benefits and potential effects on chemotherapy tolerability and efficacy. However, evidence from randomised controlled trials (RCTs) supporting...

Effect of transfer from a pediatric to adult cystic fibrosis center on clinical status and hospital attendance.

Transfer from pediatric to adult services could lead to clinical deterioration, few studies have examined this. We sought to examine the clinical impact of a structured individualized transition and transfer process in patients with cystic fibrosis (CF). Medical records of all patients with CF in Western Australia who transferred from a pediatric center (Princess Margaret Hospital for Children) to an adult CF center (Sir Charles Gairdner Hospital) between 2008 and 2012 were reviewed. Data were extracted for 2 years before and after transfer. The number of CF outpatient visits, inpatient days, and home intravenous antibiotic therapy (HIVT) days were recorded at yearly intervals before and after transfer. Sputum culture results at transfer were collected. All respiratory function and anthropometric data over the 4 years were extracted. Forty-two patients with CF were transferred between 2008 and 2012. The meanage at transfer was 18.9 years (range 17-22). Compared to 1-year pre-transfer, the frequency of outpatient visits at 1- and 2-yearpost-transfer increased. After transfer, there was no change in BMI, HIVT days, or inpatient days, and no acceleration in the expected decline in FEV1. This study found that transfer from a pediatric to an adult CF center using a structured, individualized transition and transfer process was not associated with accelerated clinical deterioration.

LOXO-305, A Next Generation, Highly Selective, Non-Covalent BTK Inhibitor in Previously Treated Mantle Cell Lymphoma, Waldenström’s Macroglobulinemia, and Other Non-Hodgkin Lymphomas: Results from the Phase 1/2 BRUIN Study

LOXO-305, A Next Generation, Highly Selective, Non-Covalent BTK Inhibitor in Previously Treated Mantle Cell Lymphoma, Waldenström’s Macroglobulinemia, and Other Non-Hodgkin Lymphomas: Results from the Phase 1/2 BRUIN Study

News

News

Journal-related Activities and Other Special Activities at the 2020 American Society of Anesthesiologists Meeting.

Journal-related Activities and Other Special Activities at the 2020 American Society of Anesthesiologists Meeting.

Hepatocyte pyroptosis and release of inflammasome particles induce stellate cell activation and liver fibrosis

Increased hepatocyte death contributes to the pathology of acute and chronic liver diseases. However, the role of hepatocyte pyroptosis and extracellular inflammasome release in liver disease is unknown. We used primary mouse and human hepatocytes, hepatocyte-specific leucine 351 to proline Nlrp3KICreA mice, and GsdmdKO mice to investigate pyroptotic cell death in hepatocytes and its impact on liver inflammation and damage. Extracellular NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasomes were isolated from mutant NLRP3-YFP HEK cells and internalisation was studied in LX2 and primary human hepatic stellate cells. We also examined a cohort of 154 adult patients with biopsy-proven non-alcoholic fatty liver disease (Sir Charles Gairdner Hospital, Nedlands, Western Australia). We demonstrated that primary mouse and human hepatocytes can undergo pyroptosis upon NLRP3 inflammasome activation with subsequent release of NLRP3 inflammasome proteins that amplify and perpetuate inflammasome-driven fibrogenesis. Pyroptosis was inhibited by blocking caspase-1 and gasdermin D activation. The activated form of caspase-1 was detected in the livers and in serum from patients with non-alcoholic steatohepatitis and correlated with disease severity. Nlrp3KICreA mice showed spontaneous liver fibrosis under normal chow diet, and increased sensitivity to liver damage and inflammation after treatment with low dose lipopolysaccharide. Mechanistically, hepatic stellate cells engulfed extracellular NLRP3 inflammasome particles leading to increased IL-1β secretion and α-smooth muscle actin expression. This effect was abrogated when cells were pre-treated with the endocytosis inhibitor cytochalasin B. These results identify hepatocyte pyroptosis and release of inflammasome components as a novel mechanism to propagate liver injury and liver fibrosis development. Our findings identify a novel mechanism of inflammation in the liver. Experiments in cell cultures, mice, and human samples show that a specific form of cell death, called pyroptosis, leads to the release of complex inflammatory particles, the NLRP3 inflammasome, from inside hepatocytes into the extracellular space. From there they are taken up by other cells and thereby mediate inflammatory and pro-fibrogenic stress signals. The discovery of this mechanism may lead to novel treatments for chronic liver diseases in the future.

Editorial introductions

Editorial introductions