Surgery (Austin & Northern Health) - Research Publications
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ItemLiver Machine Perfusion-When Physiopathology Matters(MDPI, 2022-09)Liver transplantation (LT) has become a victim of its own success [...].
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ItemEndoscopy training in Australia during COVID-19: Efficacy and knowledge assessment of gastroenterology and general surgery trainees(WILEY, 2022-12)BACKGROUND AND AIM: During COVID-19, restrictions to elective endoscopy were introduced worldwide. A reduction in procedures may impact trainees' endoscopy learning. This study aims to assess Australian advanced gastroenterology and general surgery trainees' self-perceived efficacy and knowledge in endoscopy during the pandemic. METHODS: All Australian gastroenterology and general surgery trainees in their last 2 years of accredited training were invited to participate through email (2020-2021 and 2021-2022 training cycles). The primary outcome was to assess trainees' self-efficacy and knowledge regarding gastrointestinal endoscopy. Secondary outcomes included subgroup analysis between gastroenterology and general surgery trainees. Self-perceived efficacy was assessed with Likert-scale questions on 20 endoscopy procedures and knowledge was assessed through 21 endoscopy-related multiple choice questions. RESULTS: Eighty-one trainees responded to a self-efficacy questionnaire and 77 responded to the knowledge questionnaire. Over 90% of the trainees were confident or extremely confident in diagnostic endoscopy, but only half demonstrated similar efficacy for therapeutic endoscopy. The efficacy for basic endoscopy procedures was higher for gastroenterology trainees (64.0% vs 51.1%, P < 0.001). Last-year trainee achievement of conjoint committee requirements for upper gastrointestinal endoscopy was achieved in 95.8% of gastroenterology trainees versus 22.2% of surgical trainees (P < 0.001). The median score on the knowledge questionnaire was also higher for the gastroenterology subset (90.5% vs 71.4%, P < 0.001). CONCLUSION: During COVID-19, endoscopy trainees' self-efficacy in endoscopic diagnostic procedures was achieved for most trainees. The differences in self-perceived efficacy and knowledge between gastroenterology and surgical trainees may be reflective of the different opportunities for learning between the two groups.
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ItemThe Association of Postoperative Complications and Hospital Costs Following Distal Pancreatectomy(FRONTIERS MEDIA SA, 2022-05-30)BACKGROUND: Understanding the financial implications associated with the complications post-distal pancreatectomy (DP) may be beneficial for the future optimisation of postoperative care pathways and improved cost-efficiency. The primary outcome of this retrospective study was the characterisation of the additional cost associated with postoperative complications following DP. The secondary outcome was the estimation of the prevalence, type and severity of complications post-DP and the determination of which complications were associated with higher costs. METHODS: Postoperative complications were retrospectively examined for 62 adult patients undergoing distal pancreatectomy at an Australian university hospital between January 2012 and July 2021. Complications were defined and graded using the Clavien-Dindo (CVD) classification system. In-hospital cost of index admission was calculated using an activity-based costing methodology and was reported in US dollars at 2021 rates. Regression modelling was used to investigate the relationships among selected perioperative variables, complications and costs. RESULTS: 45 patients (72.6%) experienced one or more postoperative complications. The median (IQR) hospital cost in US dollars was 31.6% greater in patients who experienced complications compared to those who experienced no complications ($40,717.8 [27,358.0-59,834.3] vs. $30,946.9 [23,910.8-46,828.1]). Costs for patients with four or more complications were 43.5% higher than for those with three or fewer complications (p = 0.015). Compared to patients with no complications, the median hospital costs increased by 17.1% in patients with minor complications (CVD grade I/II) and by 252% in patients who developed major complication (i.e., CVD grade III/IV) complications. CONCLUSION: Postoperative complications are a key target for cost-containment strategies. Our findings demonstrate a high prevalence of postoperative complications following distal pancreatectomy with number and severity of postoperative complications being associated with increased hospital costs. (Registered in the Australian New Zealand Clinical Trials Registry [No. ACTRN12622000202763]).
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ItemSAR131675, a VEGRF3 Inhibitor, Modulates the Immune Response and Reduces the Growth of Colorectal Cancer Liver Metastasis(MDPI, 2022-06)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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ItemCaptopril, a Renin-Angiotensin System Inhibitor, Attenuates Tumour Progression in the Regenerating Liver Following Partial Hepatectomy(MDPI, 2022-05)(1) Liver regeneration following partial hepatectomy for colorectal liver metastasis (CRLM) has been linked to tumour recurrence. Inhibition of the renin−angiotensin system (RASi) attenuates CRLM growth in the non-regenerating liver. This study investigates whether RASi exerts an antitumour effect within the regenerating liver following partial hepatectomy for CRLM and examines RASi-induced changes in the tumour immune microenvironment; (2) CRLM in mice was induced via intrasplenic injection of mouse colorectal tumour cells, followed by splenectomy on Day 0. Mice were treated with RASi captopril (250 mg/kg/day), or saline (control) from Day 4 to Day 16 (endpoint) and underwent 70% partial hepatectomy on Day 7. Liver and tumour samples were characterised by flow cytometry and immunofluorescence; (3) captopril treatment reduced tumour burden in mice following partial hepatectomy (p < 0.01). Captopril treatment reduced populations of myeloid-derived suppressor cells (MDSCs) (CD11b+Ly6CHi p < 0.05, CD11b+Ly6CLo p < 0.01) and increased PD-1 expression on infiltrating hepatic tissue-resident memory (TRM)-like CD8+ (p < 0.001) and double-negative (CD4-CD8-; p < 0.001) T cells; (4) RASi reduced CRLM growth in the regenerating liver and altered immune cell composition by reducing populations of immunosuppressive MDSCs and boosting populations of PD-1+ hepatic TRMs. Thus, RASi should be explored as an adjunct therapy for patients undergoing partial hepatectomy for CRLM.
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ItemPreliminary experience with continuous right ventricular pressure and transesophageal echocardiography monitoring in orthotopic liver transplantation(PUBLIC LIBRARY SCIENCE, 2022-02-04)BACKGROUND: Despite increasing attention in the cardiac anesthesiology literature, continuous measurement of right ventricular pressure using a pulmonary artery catheter has not been described in orthotopic liver transplantation, despite similarities in the anesthetic approach to the two populations. We describe our preliminary experience with this technique in orthotopic liver transplantation, and by combining various derived measures with trans-esophageal echocardiography, make some early observations regarding the response of these measures of right ventricular function during the procedure. METHODS: In this case series, ten patients (five men and five women) undergoing orthotopic liver transplantation in our institution had their surgeries performed while monitored with a pulmonary artery catheter with continuous right ventricular port transduction and trans-esophageal echocardiography. We recorded various right ventricular waveform (early-to-end diastolic pressure difference, right ventricular outflow tract gradient, right ventricular dP/dT and right ventricular end-diastolic pressure) and echocardiographic (right ventricular fractional area change, tricuspid annular plane systolic excursion, right ventricular lateral wall strain) and described their change relative to baseline at timepoints five minutes before and after portal vein reperfusion, immediately after hepatic artery reperfusion and on abdominal closure. RESULTS: Except for tricuspid annular plane systolic excursion at five minutes prior to reperfusion (mean -0.8 cm; 95% CI-1.4, -0.3; p = 0.007), no echocardiographic metric was statistically significantly different at any timepoint relative to baseline. In contrast, changes in right ventricular outflow tract gradient and right ventricular dP/dt were highly significant at multiple timepoints, generally peaking immediately before or after reperfusion before reducing, but not returning to baseline in the neohepatic phase. Nine of 10 participants in this series demonstrated a degree of dynamic right ventricular outflow tract obstruction, which met criteria for hemodynamic significance (> 25 mmHg) in two participants. These changes were not materially affected by cardiac index. CONCLUSIONS: Dynamic right ventricular outflow tract obstruction of varying severity appears common in patients undergoing orthotopic liver transplantation. These results are hypothesis generating and will form the basis of future prospective research.
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ItemEditorial: Laparoscopic and Robotic Liver Surgery(FRONTIERS MEDIA SA, 2022-02-23)
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ItemEditorial: reducing blood loss in liver transplantation-the impact of surgical technique(AME PUBL CO, 2021-11)
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ItemSARS-CoV-2 infection and venous thromboembolism after surgery: an international prospective cohort study(WILEY, 2022-01)SARS-CoV-2 has been associated with an increased rate of venous thromboembolism in critically ill patients. Since surgical patients are already at higher risk of venous thromboembolism than general populations, this study aimed to determine if patients with peri-operative or prior SARS-CoV-2 were at further increased risk of venous thromboembolism. We conducted a planned sub-study and analysis from an international, multicentre, prospective cohort study of elective and emergency patients undergoing surgery during October 2020. Patients from all surgical specialties were included. The primary outcome measure was venous thromboembolism (pulmonary embolism or deep vein thrombosis) within 30 days of surgery. SARS-CoV-2 diagnosis was defined as peri-operative (7 days before to 30 days after surgery); recent (1-6 weeks before surgery); previous (≥7 weeks before surgery); or none. Information on prophylaxis regimens or pre-operative anti-coagulation for baseline comorbidities was not available. Postoperative venous thromboembolism rate was 0.5% (666/123,591) in patients without SARS-CoV-2; 2.2% (50/2317) in patients with peri-operative SARS-CoV-2; 1.6% (15/953) in patients with recent SARS-CoV-2; and 1.0% (11/1148) in patients with previous SARS-CoV-2. After adjustment for confounding factors, patients with peri-operative (adjusted odds ratio 1.5 (95%CI 1.1-2.0)) and recent SARS-CoV-2 (1.9 (95%CI 1.2-3.3)) remained at higher risk of venous thromboembolism, with a borderline finding in previous SARS-CoV-2 (1.7 (95%CI 0.9-3.0)). Overall, venous thromboembolism was independently associated with 30-day mortality (5.4 (95%CI 4.3-6.7)). In patients with SARS-CoV-2, mortality without venous thromboembolism was 7.4% (319/4342) and with venous thromboembolism was 40.8% (31/76). Patients undergoing surgery with peri-operative or recent SARS-CoV-2 appear to be at increased risk of postoperative venous thromboembolism compared with patients with no history of SARS-CoV-2 infection. Optimal venous thromboembolism prophylaxis and treatment are unknown in this cohort of patients, and these data should be interpreted accordingly.
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ItemNo Preview AvailableSARS-CoV-2 vaccination modelling for safe surgery to save lives: data from an international prospective cohort study(OXFORD UNIV PRESS, 2021-09-27)BACKGROUND: Preoperative SARS-CoV-2 vaccination could support safer elective surgery. Vaccine numbers are limited so this study aimed to inform their prioritization by modelling. METHODS: The primary outcome was the number needed to vaccinate (NNV) to prevent one COVID-19-related death in 1 year. NNVs were based on postoperative SARS-CoV-2 rates and mortality in an international cohort study (surgical patients), and community SARS-CoV-2 incidence and case fatality data (general population). NNV estimates were stratified by age (18-49, 50-69, 70 or more years) and type of surgery. Best- and worst-case scenarios were used to describe uncertainty. RESULTS: NNVs were more favourable in surgical patients than the general population. The most favourable NNVs were in patients aged 70 years or more needing cancer surgery (351; best case 196, worst case 816) or non-cancer surgery (733; best case 407, worst case 1664). Both exceeded the NNV in the general population (1840; best case 1196, worst case 3066). NNVs for surgical patients remained favourable at a range of SARS-CoV-2 incidence rates in sensitivity analysis modelling. Globally, prioritizing preoperative vaccination of patients needing elective surgery ahead of the general population could prevent an additional 58 687 (best case 115 007, worst case 20 177) COVID-19-related deaths in 1 year. CONCLUSION: As global roll out of SARS-CoV-2 vaccination proceeds, patients needing elective surgery should be prioritized ahead of the general population.