Surgery (Austin & Northern Health) - Research Publications
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ItemSAR131675, a VEGRF3 Inhibitor, Modulates the Immune Response and Reduces the Growth of Colorectal Cancer Liver Metastasis(MDPI, 2022-06-01)Most patients with colorectal cancer (CRC) develop metastases, predominantly in the liver (CLM). Targeted therapies are being investigated to improve current CLM treatments. This study tested the effectiveness of SAR131675, a selective VEGFR-3 tyrosine kinase inhibitor, to inhibit CLM in a murine model. Following intrasplenic induction of CLM, mice were treated daily with SAR131675. Tumor growth and immune infiltrates into tumor and liver tissues were assessed at 10-, 16- and 22-days post tumor induction by stereology, IHC and flow cytometry. SAR151675 treatment significantly reduced tumor burden and F4/80+ macrophages in the liver tissues. Analysis of immune cell infiltrates in liver showed tissue that at day 22, had the proportion of CD45+ leukocytes significantly reduced, particularly myeloid cells. Analysis of myeloid cells (CD11b+ CD45+) indicated that the proportion of F4/80- Ly6Clow was significantly reduced, including a predominate PD-L1+ subset, while CD3+ T cells increased, particularly CD8+ PD1+, reflected by an increase in the CD8+:CD4+ T cell ratio. In the tumor tissue SAR11675 treatment reduced the predominant population of F4/80+ Ly6Clo and increased CD4+ T cells. These results suggest that SAR131675 alters the immune composition within tumor and the surrounding liver in the later stages of development, resulting in a less immunosuppressive environment. This immunomodulation effect may contribute to the suppression of tumor growth.
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ItemPSMA PET-CT Imaging Predicts Treatment Progression in Men with Biochemically Recurrent Prostate Cancer-A Prospective Study of Men with 3 Year Follow Up(MDPI, 2022-06-01)Prostate-specific membrane antigen (PSMA) positron emission tomography-computed tomography (PET-CT) is a novel imaging modality used to stage recurrent prostate cancer. It has the potential to improve prognostication and ultimately guide the timing of treatment for men with recurrent prostate cancer. This study aims to assess the clinical impact of PSMA PET-CT by analyzing its predictive value of treatment progression after 3 years of follow-up. In this prospective cohort study of 100 men, patients received a PSMA PET-CT for restaging of their disease which was used by a multi-disciplinary team to make a treatment decision. The primary endpoint was treatment progression. This was defined as the addition or change of any treatment modalities such as androgen deprivation therapy (ADT), radiation therapy or chemotherapy. The median follow-up time was 36 months (IQR 24-40 months). No treatment progression was found in 72 (75%) men and therefore 24 (25%) patients were found to have treatment progression. In men with a negative PSMA PET-CT result, 5/33 (15.1%) had treatment progression and 28/33 (84.8%) had no treatment progression. In conclusion, clinical decisions made with PSMA PET-CT results led to 75% of men having no treatment progression at 3 years of follow-up. In men with negative PSMA PET-CT results, this increased to 85% of men.
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ItemTransfusion-Related Renal Dysfunction After Cardiac Surgery The Role of Myeloid-Related Protein_14 in Neutrophil-Mediated Tubular Damage(ELSEVIER SCIENCE INC, 2022-07-01)Transfusion is a specific cause of acute kidney injury (AKI) after cardiac surgery. Whether there is an association between the composition of blood products and the onset of AKI is unknown. The present study suggests that the transfusion of packed red blood cells containing a high amount of myeloid-related protein 14 (MRP_14) could increase the incidence of AKI after cardiac surgery. In a mouse model, MRP_14 increased the influx of neutrophils in the kidney after ischemia-reperfusion and their ability to damage tubular cells. Higher concentrations of MRP_14 were found in packed red blood cells from female donors or prepared by whole blood filtration.
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ItemAssessing operating theatre efficiency: A prospective cohort study to identify intervention targets to improve efficiency(WILEY, 2021-06-01)BACKGROUND: Operating theatre efficiency is critical to providing optimum healthcare and maintaining the financial success of a hospital. This study aims to assess theatre efficiency, with a focus on staff activities, theatre utilisation and case changeover. METHODS: Theatre efficiency data were collected prospectively at a single centre in metropolitan Melbourne, Australia, over two 5-week periods. Characteristics of each case and various time points were collected, corresponding to either in-theatre staff activities or patient events. RESULTS: Two hundred and ninety-nine cases were prospectively audited over a range of surgical specialties. Setting up represented 42.4% (37.28 min), operating time 40.1% (35.28 min) and finishing up time 17.5% (15.43 min). Theatres were empty (turnover time) for 17.42 min, which was 39.4% of the non-operative time between operations (44.25 min, turnaround time). Plastic surgery operations required the shortest set-up and finishing times on most of the measured metrics, with general surgery and obstetrics/gynaecology having longer times. List order made a significant difference, with efficiency improving over the list and over the day for separate am and pm lists. When a patient was not on time to theatre, efficiency in both set up and finishing up metrics was significantly worse. CONCLUSIONS: A large proportion of theatre time was being spent on non-operative tasks, making staff activities potential targets for operating theatre improvement interventions. Motivation and team familiarity were identified as the major factors behind efficiently run operating theatres, supporting the use of regular operating teams and maintenance of a highly motivated workforce.
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ItemEfficacy of patient selection criteria for obesity surgery in a non-high-dependency unit/intensive care unit facility.(Wiley, 2021-07)BACKGROUNDS: Publicly funded obesity surgery remains underfunded in Australia. One barrier to expansion is the perception that perioperative care requires critical care facilities. This study evaluates the effectiveness of patient selection criteria in avoiding unplanned patient transfer and adverse outcomes in obesity surgery performed at a facility without a high-dependency unit/intensive care unit (HDU/ICU). METHODS: Retrospective analysis was performed on patients undergoing obesity surgery between January 2017 and March 2020 in a centre with specific screening criteria. Criteria included: body mass index <48 for males and <52 for females with up to three stable comorbidities from a selected list. Revision sleeve or bypass procedures were contraindicated. Primary outcome was patient transfer to our main campus. Secondary outcomes included return to theatre (RTT), readmission and death. Outcomes were compared to laparoscopic cholecystectomies (LC) performed at the same centre. RESULTS: A total of 387 obesity surgery procedures were performed; 372 patients (96%) were discharged without complication. Fifteen (3.9%) were transferred to the main campus, eight were admitted to ICU and two required re-operation. Twelve (3.1%) were readmitted within 30 days of discharge, five required re-operation. Transfer, 30-day readmission and 30-day emergency department presentation rates were similar in comparison to LC. RTT during index admission (0.5% vs. 3.0%; p = 0.006) and during 30-day post-operative period (1.8% vs. 4.4%; p = 0.025) was lower in the obesity surgery group. CONCLUSION: Carefully selected screening criteria allow obesity surgery to be performed at a well-supported non-HDU/ICU facility with few complications and acceptable rates of unplanned patient transfer.
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ItemVesico-urethral anastomosis sampling: a forgotten tool for guiding salvage radiation after radical prostatectomy(WILEY, 2021-05-01)OBJECTIVE: To review the utility of vesicourethral anastomosis (VUA)-directed biopsy in the setting of biochemical recurrence (BCR) after radical prostatectomy (RP) for prostate cancer (PCa) in patients who have undergone evaluation by gallium-68 prostate-specific membrane antigen positron emission tomography with computed tomography (68 Ga-PSMA PET/CT). METHODS: We completed a retrospective review of a prospectively maintained dataset from January 2015 to August 2020. Patient demographics were recorded for those who experienced BCR, as defined by a rise in prostate-specific antigen (PSA) level to above 0.2 ng/mL, who had a 68 Ga-PSMA PET/CT that did not demonstrate recurrence within the prostate bed, and who subsequently underwent a transperineal ultrasonography (TPUS)-guided biopsy directed at the VUA. Histological reporting of the biopsies was undertaken in order to determine whether the benefits of salvage radiation therapy (SRT) could be justified by the presence of cancer cells. RESULTS: Eighteen patients who had a 68 Ga-PSMA PET/CT and underwent VUA-directed biopsy were identified as having BCR. 68 Ga-PSMA PET/CT scans demonstrated avidity at the VUA in none of the patients, although two out of 18 patients showed avidity in the seminal vesicles and two out of 18 patients showed avidity within regional lymph nodes. Histology from the TPUS-guided, VUA-directed biopsies demonstrated no prostatic tissue in six out of 18 and presence of prostatic tissue in 12 out of 18 of patients, respectively. In 7 out of 18 cases, there was histological evidence of recurrent PCa at the VUA in the absence of a positive 68 Ga-PSMA PET/CT scan. CONCLUSION: This study highlights the potential value of VUA-directed biopsy. We are reminded that a negative 68 Ga-PSMA PET/CT does not exclude local recurrence and that the addition of a VUA-directed biopsy may aid in the decision-making process for patients with BCR following RP, especially when 68 Ga-PSMA PET/CT is locally negative. When the result of both 68 Ga-PSMA PET/CT and VUA-directed biopsy are negative, it should encourage clinicians to share decision-making in regard to undertaking SRT vs continuing BCR surveillance. This may delay the possible side effects associated with SRT, despite its excellent PSA failure-free survival rate.
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ItemSerious incidents in testicular torsion management in England, 2007-2019: optimizing individual and training factors are the key to improved outcomes.(Wiley, 2022-02)OBJECTIVES: To establish the healthcare factors that contribute to testicular torsion adverse events (orchidectomies) and 'near misses'. The secondary objective was to identify areas suitable for impactful quality improvement initiatives to be undertaken by National Health Service (NHS) healthcare providers nationally. MATERIALS AND METHODS: This was a retrospective record review and analysis, carried out in four phases. We applied the well-validated London Protocol patient safety incident analysis framework to all eligible serious incidents related to testicular torsion submitted by English NHS Trusts over a 12-year period to the Strategic Executive Information System database. Clinical reviewers established the incident population (Phase 1), were trained and piloted the feasibility of using the London Protocol (Phase 2), applied the protocol and themed the identified contributing factors linked to adverse events (orchidectomies) and near-misses (Phase 3), and reviewed the evidence for improvement interventions (Phase 4). RESULTS: Our search returned 992 serious incidents, of which 732 were eligible for study inclusion and analysis. Of those, 137 resulted in orchidectomies, equivalent to one serious incident resulting in orchidectomy per month, and 595 were near misses. Factors contributing to all incidents were: individual staff/training (38%); team (18%); work environment (16%); task and technology (14%); and institutional context (13%). Subgroup analysis of incidents resulting in orchidectomies vs near misses demonstrated a different pattern of factors, with individual staff/training factors significantly more prominent: individual/training (88%); work environment (8%); and task and technology (1%). No evidenced improvement interventions were found in the literature. CONCLUSION: This is the first study to our knowledge to systematically analyse and classify factors that are associated with loss of a testicle and related near-miss incidents in patients presenting with testicular torsion. In England, a significant number of orchidectomies occur annually as a consequence of healthcare serious incidents. In order to improve outcomes, we propose clinical support to aid the diagnosis of torsion, improved national clinical guidelines, development of specific standard operating procedures and (in the longer term) more exposure of trainees and medical students to urology to improve the testicular salvage rate.
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ItemSarcopenia is a strong predictive factor of clinical and oncological outcomes following curative colorectal cancer resection.(Wiley, 2021-05)BACKGROUND: Skeletal muscle depletion and subsequent functional loss is common in gastrointestinal malignancy. Usual markers of nutritional status may not be part of routine workup. The predictive value of sarcopenia was assessed and compared with clinically utilized factors. The aim of this was to assess the association between computed tomography assessed sarcopenia with outcomes in colorectal cancer resection. METHODS: A total of 228 consecutive patients who underwent curative colorectal cancer resection were included. Skeletal muscle area was measured at L3, with pre-defined gender-specific cut-offs applied to a height standardized index. Albumin, body mass index and Subjective Global Assessment scores were recorded alongside measures of comorbidity. Predictors of complications, mortality, and recurrence were identified through multivariate logistic regression. RESULTS: Computed tomography assessed sarcopenia was significantly associated with longer stays, complications, 30-day mortality, readmissions and recurrence at 1 year. Specific associations with major, respiratory and cardiac complications were seen. It independently predicted overall complications (odds ratio 2.96, confidence interval 1.19-7.35 P = 0.019), recurrence at 1 year (odds ratio 8.00, confidence interval 1.45-44.21, P = 0.017) and an increase in comprehensive complication index of 14 (P = 0.002). Subgroup analysis found sarcopenia predicted overall complications in rectal surgery and major complications in colonic surgery. American Society of Anesthesiologists predicted complications but not major complications while cancer stage also predicted recurrence rates. CONCLUSIONS: Sarcopenia presents an objective, available predictive factor that may be superior to current biochemical and clinical measures of nutritional and functional status. This study found it to be predictive of complication rates and recurrence after curative in colorectal cancer resection.
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ItemReduction of in-hospital cardiac arrest rates in intensive care-equipped New South Wales hospitals in association with implementation of Between the Flags rapid response system(WILEY, 2021-03-01)BACKGROUND: The NSW Clinical Excellence commission introduced the 'Between the Flags' programme, in response to the death of a young patient, as a system-wide approach for early detection and management of the deteriorating patient in all NSW hospitals. The impact of BTF implementation on the 35 larger hospitals with intensive care units (ICU) has not been reported previously. AIM: To assess the impact of 'Between the Flags' (BTF), a two-tier rapid response system across 35 hospitals with an ICU in NSW, on the incidence of in-hospital cardiac arrests and the incidence and outcome of patients admitted to an ICU following cardiac arrest and rapid response team activation. METHODS: This is a prospective observational study of the BTF registry (August 2010 to June 2016) and the Australian and New Zealand Intensive Care Society Adult Patient Database (January 2008 to December 2016) in 35 New South Wales public hospitals with an ICU. The primary outcome studied was the proportion of in-hospital cardiac arrests. Secondary outcomes included changes in the severity of illness and outcomes of cardiac arrest admissions to the ICU and changes in the volume of rapid response calls. RESULTS: The cardiac arrest rate per 1000 hospital admissions declined from 0.91 in the implementation period to 0.70. Propensity score analysis showed significant declines in ICU and hospital mortality and length of stay for cardiac arrest patients admitted to the ICU (all P < 0.001). CONCLUSIONS: The BTF programme was associated with a significant reduction in cardiac arrests in hospitals and ICU admissions secondary to cardiac arrests in 35 NSW hospitals with an ICU.