Simulation-enhanced interprofessional education (Sim-IPE) has been successfully used in various health professions and shown to improve communication and teamwork. Surgery, where preventable serious adverse outcomes are often attributed to issues with communication and teamwork, represents a compelling context for Sim-IPE. However, implementing Sim-IPE in surgery requires investment in faculty development, equipment and facilities while incurring the cost of reduced staff availability and theatre productivity during simulation activity. We conducted a scoping review to characterise how Sim-IPE in surgery is practised and researched. This scoping review followed the methodological framework described by Arksey and O’Malley. Reporting followed the PRISMA-ScR checklist. Electronic databases (Medline, EMBASE, Web of Science, PsycINFO and ERIC) were searched for records pertaining to Sim-IPE in surgery published after 1st January 2000 and in English. The final analysis included 81 articles. Simulation scenarios showed a rich variety of combinations of professions, disciplines, training levels and settings. While most scenarios used manikins (N = 54, 75

Metabolic dysfunction-associated steatohepatitis (MASH) is characterized by steatosis, inflammation, and fibrosis driven by hepatic stellate cell (HSC) activation. Acetyl-CoA is central to de novo lipogenesis (DNL) and cholesterol synthesis and is generated from citrate via ATP citrate lyase (ACLY) or from acetate via acetyl-CoA synthetase (ACSS2). Here, we demonstrate that a dual inhibitor of ACLY and ACSS2, EVT0185, reduces serum and liver triglycerides, insulin resistance, and fibrosis. EVT0185 directly suppresses HSC activation in vivo and in vitro, with spatial transcriptomics and single-cell RNA sequencing revealing inhibition of acetate metabolism via ACSS2 and cholesterol synthesis as key drivers of the phenotype. EVT0185 also inhibits de novo lipogenesis in human liver slices and blocks TGFβ1-induced activation of primary human HSCs. These findings suggest that targeting cholesterol and acetate metabolism through dual ACLY and ACSS2 inhibition represents a promising therapeutic approach for MASH and liver fibrosis.

BackgroundPancreatic ductal adenocarcinoma (PDAC) is a major cause of cancer-related deaths in Australia, with a 5-year survival rate of less than 13%. The liver is the most common site of PDAC metastasis, and is observed in over 50% of cases. Standard chemotherapy, including regimens such as FOLFIRINOX or nab-paclitaxel plus gemcitabine, offer limited survival benefits, with median survival rates typically below one year. Selective internal radiation therapy (SIRT) with Yttrium-90 (90Y) microspheres is used to target liver metastases, but the optimal chemotherapy companion for SIRT in metastatic PDAC remains unknown.MethodsWe conducted a retrospective audit of 32 patients with metastatic PDAC treated with SIRT and chemotherapy, and evaluated the clinical outcomes associated with platinum-based versus non-platinum-based regimens.ResultsPatients who received platinum-based chemotherapy alongside SIRT had a median PFS of 10 months, compared to 2 months in those treated with non-platinum-based regimens. Stratified analysis revealed that patients receiving platinum-based chemotherapy in the first-line setting achieved a median post-SIRT survival of 16 months, compared to 4 months for those treated in later lines. For non-platinum-based regimens, median post-SIRT survival was 9 months in the first-line and 6 months in later lines. Median OS from Stage IV diagnosis was 17 months for patients with liver-only metastases and 15 months for those with additional extra-hepatic disease, suggesting that liver disease burden remains a dominant driver of outcomes.ConclusionsThese findings describe survival outcomes among patients treated with SIRT and chemotherapy for metastatic PDAC in a real-world setting. Longer observed survival was seen in patients who received platinum-based chemotherapy alongside SIRT, particularly in the first-line setting. Given the descriptive design and small sample size, these findings should be interpreted as hypothesis-generating and may inform future prospective evaluation of SIRT-chemotherapy combinations.

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy with a poor prognosis. While immunotherapy has shown limited efficacy in most PDAC cases due to an immunosuppressive tumour microenvironment, tumours with microsatellite instability-high (MSI-H) or deficient mismatch repair (dMMR) status exhibit increased responsiveness to immune checkpoint inhibitors. We report the case of a 45-year-old woman with Lynch syndrome who was diagnosed with MSI-H/dMMR PDAC during routine surveillance. Given the borderline resectable nature of her tumour and previous chemotherapy-related neurotoxicity, she was treated with neoadjuvant pembrolizumab instead of conventional chemotherapy. Following four cycles of pembrolizumab, imaging revealed a marked metabolic response, allowing for successful R0 pancreatoduodenectomy. Postoperative histology confirmed a significant reduction in tumour size, and immunohistochemical analysis demonstrated increased CD8 + T cell infiltration, supporting an enhanced anti-tumour immune response. The patient continues adjuvant pembrolizumab therapy without complications. This case highlights the potential role of neoadjuvant pembrolizumab in MSI-H/dMMR PDAC, demonstrating successful tumour downstaging and facilitating surgical resection. Our findings support further investigation into the integration of immunotherapy as a neoadjuvant strategy for select PDAC patients.

Importance Patients undergoing unplanned abdominal surgical procedures are at increased risk of surgical site infection (SSI). It is not known if incisional negative pressure wound therapy (iNPWT) can reduce SSI rates in this setting. Objective To evaluate the effectiveness of iNPWT in reducing the rate of SSI in adults undergoing emergency laparotomy with primary skin closure. Design, Setting, and Participants SUNRRISE was an assessor-masked, pragmatic, phase 3, individual-participant, randomized clinical trial. Adult patients undergoing emergency laparotomy in 22 hospitals in the UK and 12 hospitals in Australia between December 18, 2018, and May 25, 2021, were recruited. Patients were followed up for 30 days postprocedure; database closure was on August 25, 2021. Interventions Participants were randomized 1:1 to receive iNPWT (n = 411), which involved a specialized dressing used to create negative pressure over the closed wound vs the surgeon’s choice of wound dressing (n = 410). Randomization and dressing application occurred in the operating room at the end of the surgical procedure. Main Outcomes and Measures The primary outcome measure was SSI up to 30 days postprocedure, evaluated by an assessor masked to the randomized allocation and using criteria from the US Centers for Disease Control and Prevention. There were 7 secondary outcomes, including length of hospital stay, postoperative complications up to 30 days, hospital readmission for wound-related complications within 30 days, wound pain, and quality of life. Results A total of 840 patients were randomized (536 from the UK; 304 from Australia). Overall, 52% were female; the mean age was 63.8 (range, 18.8 to 95.3) years. After postrandomization exclusions (N = 52), 394 participants per group were included in the primary analysis. The number of participants who had an SSI in the iNPWT group was 112 of 394 (28.4%), compared with 108 of 394 (27.4%) in the surgeon’s preference group (relative risk, 1.03 [95% CI, 0.83-1.28]; P = .78). This finding was consistent across the preplanned subgroup analyses, including degree of contamination, presence of a stoma, participant body mass index, and skin preparation used, and across all preplanned sensitivity analyses. Of 7 secondary outcomes, 6 showed no significant difference, including hospital readmission, quality of life, and hospital stay (median [IQR], 8 [6-14] days in the iNPWT group and 9 [6-14.5] days in the surgeon’s preference group [ratio of geometric means, 0.96 (95% CI, 0.88-1.06); P = .21]). Conclusions and Relevance Routine application of iNPWT to the closed surgical wound after emergency laparotomy did not prevent SSI more than other dressings. Trial Registration isrctn.com Identifier: ISRCTN17599457 ; anzctr.org.au Identifier: ACTRN12619000496112

BACKGROUND:Postoperative pancreatic fistula (POPF) is the primary cause of morbidity after distal pancreatectomy (DP). This trial investigated the application of a combined polyethylene glycol (PEG) and recombinant human albumin sealant gel to the stapled, transected pancreatic margin to reduce clinically significant POPF. METHODS:A multicenter randomised controlled trial in patient candidates for DP with stapled transection was conducted. Participants were randomised to receive DP with or without PEG sealant applied to the stapled margin. The primary outcome was clinically significant POPF. Secondary outcomes included other complications, length of hospital stay and 90-day mortality. RESULTS:Seventy-eight patients with completed DP were included, 38 of whom underwent stapled DP combined with the use of PEG sealant (PEG group). No significant differences between the two groups were observed with respect to pathology type, operative approach or operative time. The PEG group exhibited significantly fewer complications (18% vs. 50% in the control group; p = 0.003), and a lower rate of POPF (11% vs. 28%; p = 0.08, respectively). Multivariate analysis revealed a significant association between spleen preservation and the rate of clinically significant fistula (OR 4.4; 95% CI 1.1-18.0; p = 0.038). The rate of POPF was lower in the PEG group but did not reach statistical significance (OR 0.3; 95% CI 0.1-1.2; p = 0.091). CONCLUSION:Stapled DP combined with PEG application was associated with reduced complications. There was a lower rate of POPF in the PEG sealant group that did not reach statistical significance. AUSTRALIAN NEW ZEALAND CLINICAL TRIALS REGISTRY:ACTRN12620001336976p.

INTRODUCTION:Upon graduation, newly qualified doctors are expected to manage complex and unwell patients, and adapt their prior learning to navigate an often-nuanced healthcare workplace environment. Surgical rotations can bring a unique set of learning curves and challenges to this already demanding transitional period. The aim of this study was to identify the training needs of medical students and early-career doctors in surgical skills, incorporating viewpoints from all stakeholder groups to provide a holistic insight into the provision of surgical education currently, and how it can be optimized to improve work preparedness. METHODS:Final-year medical students, interns and clinical educators from five clinical schools affiliated with the University of Melbourne were recruited for semi-structured interviews. Following transcription, multi-phased thematic analysis was performed to identify key themes. RESULTS:Thirty-seven participants were interviewed (18 students, 8 interns and 11 clinical educators). Outside of commonly utilized procedural skills, different emphases were placed on non-technical skills by students and interns, compared to clinical educators. Increased hands-on learning and structured teaching were thought to be key to increasing confidence and work preparedness. CONCLUSION:This qualitative study interviewed key stakeholders to identify important skills in order to help newly qualified interns to thrive in a surgical rotation. These skills in particular included more supervised hands-on practical teaching. Future studies involving graduates from other medical schools may provide a better understanding of surgical education in the wider Australian context.

Purpose:We primarily evaluated the relationship between postoperative complications and long-term survival in patients undergoing major gastrointestinal surgery. Secondarily, we investigated the relationship between the severity and the number of complications and long-term survival. While postoperative complications are prevalent after major abdominal surgery and associated with increased mortality, the effect of their severity and accumulation remains insufficiently explored. Patients and Methods:1989 adult patients undergoing major gastrointestinal surgery between July 2010 and April 2022 were retrospectively studied. Complications were classified using the Clavien-Dindo system. Kaplan-Meier analysis assessed long-term survival, Cox proportional hazards regression with time-dependent coefficients evaluated the impact of complications on mortality. Results:Median age was 64 years (IQR 53-74); 41.8% female and 63.0% of patients were diagnosed with malignancy. Elective procedures comprised 73.0% of cases. Complications occurred in 74.6% of patients. Mortality was higher in patients with complications (32.0%, 95% CI 29.7%-34.5%), compared to those without (21.7%, 95% CI 18.3-25.6%; P<0.001). Severe complications (Clavien-Dindo Grade ≥III) were associated with a 15.01-fold higher hazard of mortality within 18 months postoperatively (95% CI 6.83-33.0; P<0.001). Conclusion:Postoperative complications significantly reduce long-term survival following major gastrointestinal surgery. Both their severity and frequency are critical determinants of poorer outcomes, emphasizing the need for effective prevention strategies.

622 Background: Selective internal radiation therapy (SIRT) using Yttrium-90 containing microspheres has established benefit for a number of cancers but there is limited data available on the utility of SIRT for the treatment of metastatic pancreatic ductal adenocarcinoma (PDAC). Methods: In this retrospective audit we identified 32 patients who received SIRT using Yttrium-90 microspheres for metastatic PDAC in 2 treatment centres. All patients received SIRT in combination with chemotherapy. Data was analysed from electronic medical records. Results: Thirty two patients with metastatic PDAC who had SIRT were identified. Patients received SIRT (median activity 1.6 GBq) in combination with chemotherapy (platinum-based; n = 23, non-platinum-based; n = 9). Three patients remain alive and 29 patients were included in the survival analysis. For the entire group, the median OS was 15 months (range 4-49), median survival from time of SIRT was 9 months (range 1-48) and median PFS from time of SIRT was 4 months (range 1-25). Median PFS (6 vs 2 months, p=0.0011) and OS (13 vs 4 months, p=0.0004) from SIRT was significantly better when SIRT was given with 1st-line therapy vs with 2nd-line and beyond. Median PFS from SIRT was significantly better (10 vs 2 months, p=0.0020) when combined with 1st line platinum-based chemotherapy (n=14) vs non-platinum based treatment (n=6). 18 month survival was 40% (n=13) with 9/13 patients having had SIRT with 1st line with platinum-based therapy. 24 month survival was 22% (n=7) with 7/7 patients having had SIRT with 1st line with platinum-based therapy. SIRT was well-tolerated with no associated 30-day all-cause mortality. Grade 3 adverse events were liver abscess (7%, n = 2), gastritis (7%, n = 2) and duodenitis (7%, n=2). Conclusions: This is the first report to analyse optimum utility of SIRT with chemotherapy in metastatic PDAC. Our data suggest SIRT in combination with 1st-line platinum agents contribute to the best outcomes in the setting and warrants further study.

BACKGROUND Cost analyses of patients undergoing esophagectomy is valuable for identifying modifiable expenditure drivers to target and curtail costs while improving the quality of care. We aimed to define the cost-complication relationship after esophagectomy and delineate the incremental contributions to costs. AIM To assess the relationship between the hospital costs and potential cost drivers post esophagectomy and investigate the relationship between the cost-driving variables (predicting variables) and hospital costs (dependent variable). METHODS In this retrospective single center study, the severity of complications was graded using the Clavien-Dindo (CD) classification system. Key esophagectomy complications were categorized and defined according to consensus guidelines. Raw costing data included the in-hospital costs of the index admission and any unplanned admission within 30 postoperative days. We used correlation analysis to assess the relationship between key clinical variables and hospital costs (in United States dollars) to identify cost drivers. A mediation model was used to investigate the relationship between these variables and hospital costs. RESULTS A total of 110 patients underwent primary esophageal resection. The median admission cost was $47822.7 (interquartile range: 35670.2-68214.0). The total effects on costs were $13593.9 (95%CI: 10187.1-17000.8, P < 0.001) for each increase in CD severity grade, $4781 (95%CI: 3772.7-5789.3, P < 0.001) for each increase in the number of complications, and $42552.2 (95%CI: 8309-76795.4, P = 0.015) if a key esophagectomy complication developed. Key esophagectomy complications drove the costs directly by $11415.7 (95%CI: 992.5-21838.9, P = 0.032). CONCLUSION The severity and number of complications, and the development of key esophagectomy complications significantly contributed to total hospital costs. Continuous institutional initiatives and strategies are needed to enhance patient outcomes and minimize costs.

The presence of precursor to exhausted (T-pex) CD8(+) T cells is important to maintain robust immunity following treatment with immune checkpoint inhibition (ICI). Impressive responses to ICI are emerging in patients with stage II-III mismatch repair (MMR)-deficient (dMMR) colorectal cancer (CRC). We found 64% of dMMR and 15% of mismatch repair-proficient (pMMR) stage III CRCs had a high frequency of tumor infiltrating lymphocytes (TIL-hi). Furthermore, expression of TCF-1 (Tcf7) by CD8(+) T cells predicted improved patient prognosis and T(pex )cells (CD3(+)CD8(+)TCF-1(+)PD-1(+)) were abundant within lymphoid aggregates of stage III CRCs. In contrast, CD3(+)CD8(+)TCF-1(-)PD-1(+ )cells were more abundant at the invasive front and tumor core, while gamma delta T cells were equally abundant in all tumor areas. Interestingly, no differences in the frequency of T-pex cells were observed between TIL-hi dMMR and TIL-hi pMMR CRCs. Therefore, T-pex cell function and ICI response rates in TIL-hi CRC warrants further investigation.

BACKGROUND Liver transplantation (LT) is a potentially curative therapy for patients with hepatocellular carcinoma (HCC). HCC-recurrence following LT is associated with reduced survival. There is increasing interest in chemoprophylaxis to improve HCC-related outcomes post-LT. AIM To investigate whether there is any benefit for the use of drugs with proposed chemoprophylactic properties against HCC, and patient outcomes following LT. METHODS This was a retrospective study of adult patients who received Deceased Donor LT for HCC from 2005-2022, from a single Australian centre. Drug use was defined as statin, aspirin or metformin therapy for ≥ 29 days, within 24 months post-LT. A cox proportional-hazards model with time-dependent covariates was used for survival analysis. Outcome measures were the composite-endpoint of HCC-recurrence and all-cause mortality, HCC-recurrence and HCC-related mortality. Sensitivity analysis was performed to account for immortality time bias and statin dosing. RESULTS Three hundred and five patients were included in this study, with 253 (82.95%) males with a median age of 58.90 years. Aetiologies of liver disease were 150 (49.18%) hepatitis C, 73 (23.93%) hepatitis B (HBV) and 33 (10.82%) non-alcoholic fatty liver disease (NAFLD). 56 (18.36%) took statins, 51 (16.72%) aspirin and 50 (16.39%) metformin. During a median follow-up time of 59.90 months, 34 (11.15%) developed HCC-recurrence, 48 (15.74%) died, 17 (5.57%) from HCC-related mortality. Statin, aspirin or metformin use was not associated with statistically significant differences in the composite endpoint of HCC-recurrence or all-cause mortality [hazard ratio (HR): 1.16, 95%CI: 0.58-2.30; HR: 1.21, 95%CI: 0.28-5.27; HR: 0.61, 95%CI: 0.27-1.36], HCC-recurrence (HR: 0.52, 95%CI: 0.20-1.35; HR: 0.51, 95%CI: 0.14-1.93; HR 1.00, 95%CI: 0.37-2.72), or HCC-related mortality (HR: 0.32, 95%CI: 0.033-3.09; HR: 0.71, 95%CI: 0.14-3.73; HR: 1.57, 95%CI: 0.61-4.04) respectively. Statin dosing was not associated with statistically significant differences in HCC-related outcomes. CONCLUSION Statin, metformin or aspirin use was not associated with improved HCC-related outcomes post-LT, in a largely historical cohort of Australian patients with a low proportion of NAFLD. Further prospective, multicentre studies are required to clarify any potential benefit of these drugs to improve HCC-related outcomes.

BACKGROUND:Ex vivo normothermic machine perfusion (NMP) is an organ preservation technique that enables an extended assessment of graft suitability before liver transplantation (LT). Established monitoring protocols used during NMP vary significantly in their assessment of transplant suitability when applied to the same grafts. Graft-derived cell-free DNA (gdcfDNA) analysis is an emerging tool for monitoring graft health post-transplantation. We investigated the feasibility of monitoring gdcfDNA during NMP for LT in a proof-of-concept, observational study. METHODS:Serial plasma and bile samples were collected during NMP for 10 consecutive grafts, at 15 min post-machine reperfusion and then 2-h intervals. Digital polymerase chain reaction was used to quantify gdcfDNA at each time point. RESULTS:Five grafts were suitable for LT, there were no cases of primary nonfunction or death in the recipients. gdcfDNA was quantified in all bile and plasma samples (n > 100). In plasma, gdcfDNA concentrations climbed post-machine reperfusion until 4.25 h (median 2.25 h = 15.98 × 10 6 copies/mL, 4.25 h = 40.21 × 10 6 copies/mL). gdcfDNA levels then diverged significantly when comparing the viable and non-viable graft groups (6.25 h, median viable: 117.15 × 10 6 copies/mL versus non-viable: 16.72 × 10 6 copies/mL, P  = 0.01). These opposing trends correlated in each graft and in all cases with the viable/non-viable outcome. There was a trend of gradual decline in bile gdcfDNA from viable grafts post-machine reperfusion; discarded grafts showed more variable patterns of release. CONCLUSIONS:gdcfDNA analysis during NMP is a feasible and potential tool to inform viability assessment during NMP for LT. Bile gdcfDNA monitoring offers the prospect of an objective means to assess the degree of biliary injury associated with organ procurement.

Objective Postoperative complications following major abdominal surgeries is a pressing concern for hospital care and health economics. Given the paucity of available cost data for patients undergoing major abdominal surgery, we evaluated the number and the severity of postoperative complications following major abdominal surgeries and calculated the costs borne by a single centre university hospital within an Australian healthcare system. Results The overall incidence of postoperative complications for 1790 adult patients undergoing major abdominal surgeries (i.e., colonic, liver, small bowel resections and Whipple procedures) between January 2013 and June 2018 was 75.2%. Of these complications, 56.9% were minor (Clavien–Dindo (CVD) Grades I or II) and 15.5% were major (CVD Grades III or IV). As the severity of complications increased, median adjusted total hospital costs rose significantly, with a median (interquartile range [IQR]) of AUD 29,519.70 (IQR 21,828.80–40,527.90) in CVD Grade II versus AUD 50,702.40 (IQR 35,866.00–69,296.80) in CVD Grade III ( p <.001). Further, developing one, two or three complications resulted in significantly increased hospital costs by AUD 2618.30 (13.3% increase), AUD 3605.50 (16.2% increase) and AUD 3173.00 (12.3% increase) ( p < .0001), respectively, with an exponential spike in costs incurred by patients who developed more than three complications (AUD 23,719.70; 81.7% increase; p < 0001).