PURPOSE:Graft pancreatitis (GP) is a complication of pancreas transplantation. Currently no standardised diagnostic criteria for this condition exists. The purpose of this review is to identify potential associated and mitigating factors for the development of GP. METHODOLOGY:MEDLINE and EMBASE databases were systematically searched. Studies reporting GP development after pancreas transplantation were included. Bias was assessed using the Newcastle-Ottawa Scale and Cochrane Risk of Bias tools. RESULTS:Fifty-eight studies were included. Potential associated factors for GP included donor age, duration of cold ischemia time, recipient pre-transplant lipid levels, HTK preservation, learning phase of a transplant program, exocrine bladder drainage, implantation order during simultaneous pancreas-kidney transplantation, and recipient reperfusion mean arterial pressure. Potential mitigating factors include use of intraoperative sevoflurane and desflurane, donor steroid pre-treatment and recipient pre-treatment with calcium channel blockers and anti-thrombin III. CONCLUSION:This systematic review identified a range of potential associated factors and mitigating factors for graft pancreatitis.

Anastomotic time (AT), also termed second warm ischaemic time (SWIT), is a potentially important intraoperative factor in kidney transplantation, yet its impact on outcomes has not been systematically synthesised. We conducted a systematic review to examine the association between AT and delayed graft function (DGF), graft survival, and patient survival. Cochrane, Embase, and Medline were searched to 21 July 2025. Nine retrospective cohort studies comprising 155,523 transplants were included. Across all donor types, longer AT was consistently associated with higher rates of DGF within individual studies. Several studies also reported poorer 1- and 5-year graft survival with prolonged AT, while findings for patient survival were equivocal. However, substantial heterogeneity across studies, including donor type, AT definitions, outcome reporting, and incomplete adjustment for key confounders, precluded formal meta-analysis. None of the included studies consistently adjusted for major determinants of graft outcomes. These findings suggest a potential link between prolonged AT and adverse graft outcomes, but high-quality prospective studies with standardised reporting and confounder adjustment are required before AT can be considered an independent determinant of transplant outcomes.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/, identifier PROSPERO CRD42024549222.

Metabolic dysfunction-associated fatty liver disease (MAFLD) is now the leading cause of hepatocellular carcinoma (HCC) globally. HCC surveillance is currently restricted to patients with cirrhosis, leaving those without cirrhosis, who present with more advanced disease and poorer outcomes without adequate risk stratification tools. This study compared lipid profiles across MAFLD and MAFLD-related HCC (MAFLD-HCC) patients, with and without cirrhosis, to characterise metabolic dysregulation underlying non-cirrhotic MAFLD-HCC (ncMAFLD-HCC). Plasma and liver lipidomic profiles were obtained from 221 patients (140 MAFLD, 66 cirrhotic MAFLD-HCC (cMAFLD-HCC), and 15 ncMAFLD-HCC) using untargeted liquid chromatography mass spectrometry. Univariate, multivariable and enrichment analyses were performed for statistically determining the lipid profile difference between the groups. Seventy percent of lipid classes were more abundant in MAFLD than in ncMAFLD-HCC and cMAFLD-HCC. Multivariate analysis revealed distinct lipid profiles across the three groups in both plasma and liver. Over 100 lipid species including diglyceride (DAG), sphingomyelin (SM), triglyceride (TG), dihydroceramide (DHCer), and linoleic acid derivatives were differentially expressed in ncMAFLD-HCC versus MAFLD, with enrichment in pathways such as glycerolipid metabolism, G-protein signalling, MAPK signalling, EGFR-TKI resistance pathway, implicated in HCC development. ncMAFLD-HCC exhibits a distinct lipid signature, offering preliminary mechanistic insight and a foundation for non-invasive biomarker development.

ABSTRACTBackgroundFXYD3 is a Na/K‐ATPase modulator which is upregulated in pancreatic ductal adenocarcinoma (PDAC), but its prognostic role is unknown. This study evaluated FXYD3 expression in chemo‐naive patients with surgically‐resected PDAC at a single centre (1993–2014).MethodFXYD3 expression was assessed in tumour specimens using immunohistochemistry.Results145 of 180 PDAC tumour specimens were FXYD3‐immunopositive (80.5%). There was no difference in median overall survival between the FXYD3 negative (27.60 months) and positive groups (25.00 months) (log‐rank p = 0.9718). FXYD3 expression correlated positively with late‐stage disease (OR 3.041, 95% CI 1.190–7.455, p = 0.0175). There was no significant association with T stage, positive lymph nodes, perineural invasion, lymphovascular invasion or histological grade.ConclusionImmunohistochemical FXYD3 expression does not predict survival in chemo‐naive PDAC patients, but is associated with late‐stage disease. The high rate of FXYD3 overexpression warrants therapeutic evaluation.

Background: Hepatocellular carcinoma (HCC) is a major global health issue, in which the underlying liver disease aetiology has shifted towards non-viral causes, particularly metabolic (dysfunction)-associated fatty liver disease (MAFLD). While traditionally associated with cirrhosis, a subset of HCC cases arises in patients with MAFLD but without cirrhosis, whose characteristics remain poorly understood. Objectives: The study aims to explore the clinical, tumour and genetic characteristics of non-cirrhotic MAFLD-related HCC when compared to those that develop in the context of cirrhosis. Design: A multi-centre, retrospective study of 89 MAFLD-related HCC patients enrolled between 2009 and 2023 was performed. Methods: We conducted a study of well-defined MAFLD-related HCC patients to explore their MAFLD-related clinical and genetic associations. Statistical analysis was undertaken to compare the underlying cirrhosis and non-cirrhosis groups for HCC features, adjusting for relevant confounders. Results: Patients with HCC arising in cases of MAFLD without cirrhosis exhibited a lower body mass index, higher triglyceride levels and increased smoking prevalence compared to their counterparts with cirrhosis. Despite arising in the absence of cirrhosis, these patients had more aggressive tumour features, including larger tumour size, multifocality and portal vein thrombosis. Logistic regression confirmed non-cirrhosis status to be an independent predictor of larger tumour size and increased lesion number. Conclusion: Non-cirrhotic MAFLD-related HCC presents with distinct clinical and tumour characteristics, suggesting the existence of unique disease drivers that are yet to be discovered.

BACKGROUND:There is conflicting evidence regarding the efficacy of normothermic machine perfusion (NMP) in suboptimal deceased donor kidneys. We aimed to assess the feasibility and short-term efficacy of brief preimplantation NMP in circulatory death (DCD) kidneys. METHODS:In this nonrandomized, single-center, prospective clinical trial, DCD kidneys underwent 1 to 3 h of NMP before implantation, aiming to achieve short ischemic times off NMP. The primary outcomes included feasibility and safety. Secondary outcomes included efficacy outcomes (delayed graft function and estimated glomerular filtration rate (eGFR) at 1, 6, and 12 mo), which were compared with the contralateral kidney that did not receive NMP. RESULTS:Eighteen DCD kidneys underwent NMP between 2020 and 2022, with at least 1 h completed in 16 (88.9%) of these kidneys (median 1 h); 1 kidney was removed after 5 min because of cannula failure and another at 54 min because of a sudden drop in blood flows. There was no episode of graft loss on the machine or postoperative vascular thromboses. All 18 kidneys were transplanted, with no cases of PNF or graft loss at 12 mo. Seventeen of the contralateral CS kidneys were transplanted. Compared with the contralateral kidneys, a lower incidence of delayed graft function (23.5% versus 64.7%; P  = 0.046) was observed. There were no differences in the eGFR slopes between the 2 groups over time ( P  = 0.254). CONCLUSIONS:NMP is safe, feasible and efficacious in the Australian setting, with this relatively small cohort demonstrating good early outcomes compared to CS alone in our study of DCD kidneys.

OBJECTIVE:Postoperative pancreatic fistula (POPF) represents a leading cause of morbidity and mortality following major pancreatic resections. This study aimed to evaluate the use of postoperative drain fluid lipase-to-amylase ratio (LAR) for the prediction of clinically relevant fistulae (CR-POPF). METHODS:Consecutive patients undergoing pancreaticoduodenectomy between 2017 and 2021 at a tertiary centre were retrospectively reviewed. Univariable and multivariable analyses were performed to identify predictors for CR-POPF (ISGPS grade B/C). Receiver operating characteristic (ROC) curve analyses were conducted to evaluate the performance of LAR and determine optimum prediction thresholds. RESULTS:Among 130 patients, 28 (21.5%) developed CR-POPF. Variables positively associated with CR-POPF included soft gland texture, acinar cell density, diagnosis other than PDAC or chronic pancreatitis, resection without neoadjuvant therapy, and postoperative drain fluid lipase, amylase, and LAR (all P <0.05). Multivariable regression analysis identified LAR as an independent predictor of CR-POPF ( P <0.05). ROC curve analysis showed that LAR had moderate ability to predict CR-POPF on POD1 (AUC,0.64; 95%CI,0.54-0.74) and excellent ability on POD3 (AUC,0.85; 95%CI,0.78-0.92) and POD 5 (AUC,0.86; 95%CI,0.79-0.92). Optimum thresholds were consistent over PODs 1 to 5 (ratio>2.6) and associated with 92% sensitivity and 46% to 71% specificity. CONCLUSIONS:Postoperative drain fluid LAR represents a reliable predictor for the development of CR-POPF. With early prognostication, the postoperative care of patients at risk of developing high-grade fistulas may be optimized.

Background The COVID-19 pandemic has brought significant changes to medical education, particularly for procedural and surgical skills, which inherently require face-to-face education. The utility of adding an instructional video remains uncertain. To guide future curricula, our aim was to assess whether the addition of an optional instructional video improves the acquisition and retention of one-handed surgical knot-tying. Methods Naïve year one medical students were randomised to video before face-to-face instruction versus face-to-face instruction only. Blinded surgeons assessed their performance at the end of a workshop and 4 weeks later by counting the number of knots tied in 1 min and a global Likert score assessing knot quality. The students also completed surveys for qualitative assessment and feedback. Results Students with access to the video tied significantly more knots in 1 min than the control group (median ± IQR: 15 ± 4 N = 14, vs 12.5 ± 10 N = 15, p = 0.012). After 4 weeks, the intervention group showed a non-significant trend towards being able to tie more knots (16.5 ± 6 N = 6, vs 3.5 ± 16 N = 8, p = 0.069), and the knots tied were of significantly better quality (global score: 3 ± 1.4 vs 1 ± 1.8, p = 0.027). Compared to the control group, the intervention group expressed greater confidence in their ability to retain their skills after the workshop and at follow-up (p = 0.04). Additionally, they experienced significantly less stress during the workshop (p = 0.028). Conclusion A non-interactive video can improve learning and retention of single-handed knot tying. As medical education continues to evolve, supplementary videos should be considered an important part of new surgical skill curricula.

OBJECTIVES:While emergency cholecystectomy is the preferred treatment for acute cholecystitis, conservative management can be used as a bridge to definitive surgical management in situations where emergency surgical services are limited. The objective of this systematic review is to identify factors associated with conservative management failure as defined as either failed resolution of symptoms on initial presentation, or the recurrence of symptoms whilst awaiting an elective cholecystectomy. This study aims to allow clinicians to make evidence-based recommendations for conservative versus operative management. METHODS:A systematic review of the Medline database was conducted in May 2022 to identify studies analysing the success of non-operative management of acute cholecystitis. Two independent reviewers selected studies based on predefined criteria, and the risk of bias was evaluated. Out of the initial 1344 studies retrieved, 12 studies met the inclusion criteria. RESULTS:Factors significantly associated with persistence of symptoms in at least one study on multivariable analysis included diabetes mellitus, age >70, tachycardia, elevated temperature, elevated white cell count >15 000/uL and a distended gallbladder >5 cm. Factors significantly associated with recurrence of symptoms included Age <40 or >80, male sex, acute cholecystitis grade 2 or 3, elevated creatinine, serum albumin <4 g/dL, thickened gallbladder wall >5 mm. CONCLUSION:Several factors have been identified which may facilitate future evidence-based recommendations for tailored management strategies for patients with acute cholecystitis.

Background. Uncontrolled donation after circulatory death (uDCD) is a potential additional source of donor kidneys. This study reviewed uDCD kidney transplant outcomes to determine if these are comparable to controlled donation after circulatory death (cDCD). Methods. MEDLINE, Cochrane, and Embase databases were searched. Data on demographic information and transplant outcomes were extracted from included studies. Meta-analyses were performed, and risk ratios (RR) were estimated to compare transplant outcomes from uDCD to cDCD. Results. Nine cohort studies were included, from 2178 uDCD kidney transplants. There was a moderate degree of bias, as 4 studies did not account for potential confounding factors. The median incidence of primary nonfunction in uDCD was 12.3% versus 5.7% for cDCD (RR, 1.85; 95% confidence intervals, 1.06-3.23; P = 0.03, I2 = 75). The median rate of delayed graft function was 65.1% for uDCD and 52.0% for cDCD. The median 1-y graft survival for uDCD was 82.7% compared with 87.5% for cDCD (RR, 1.43; 95% confidence intervals, 1.02-2.01; P = 0.04; I2 = 71%). The median 5-y graft survival for uDCD and cDCD was 70% each. Notably, the use of normothermic regional perfusion improved primary nonfunction rates in uDCD grafts. Conclusions. Although uDCD outcomes may be inferior in the short-term, the long-term outcomes are comparable to cDCD.

INTRODUCTION:Unplanned readmissions in general surgery are an important quality indicator of patient care and are associated with increased costs to healthcare services. This study aims to implement a multidisciplinary protocol in a single institution in a tertiary referral hospital to monitor and reduce unplanned readmission rates. METHODS:A prospective cohort study using an institution-based protocol was conducted over an 18-month period including patients undergoing a general surgical procedure. The protocol included: (i) implementation of a surgical readmissions nurse-patient liaison; (ii) access to a surgical walk-in clinic; and (iii) early post-discharge phone contact. Data included demographic details, index procedure, hospital length of stay (LOS), and whether contact between patient/nurse occurred upon discharge. The primary outcome was the cause and rate of 30-day readmissions. Secondary outcomes were mortality, use of surgical clinic, emergency department presentations, and complications. RESULTS:After protocol implementation, 874 patients underwent a general surgical procedure, with 354 (49%) being male and an overall median age of 53.0 years (interquartile range: 36.0-67.0). The overall readmission rate was 5.6% (n = 49), with a median LOS after readmission of 4 days. Compared with historical pre-protocol ACS-NSQIP data, this reflects a 30% reduction compared to that of readmission rate of 7.9%, P = 0.03. CONCLUSION:The multidisciplinary protocol was efficacious in significantly reducing unplanned readmissions. Continued audits and monitoring of factors associated with readmissions are required to help design targeted projects that may lead to improved outcomes, lower costs, increased patient satisfaction, and better efficiency within our healthcare system.

Perihilar cholangiocarcinoma (pCCA) is an uncommon malignancy with generally poor prognosis. Surgery is the primary curative treatment; however, the perioperative mortality and morbidity rates are high, with a low 5-year survival rate. Use of preoperative prognostic biomarkers to predict survival outcomes after surgery for pCCA are not well-established currently. This systematic review aimed to identify and summarise preoperative biomarkers associated with survival in pCCA, thereby potentially improving treatment decision-making. The Embase, Medline, and Cochrane databases were searched, and a systematic review was performed using the PRISMA guidelines. English-language studies examining the association between serum and/or tissue-derived biomarkers in pCCA and overall and/or disease-free survival were included. Our systematic review identified 64 biomarkers across 48 relevant studies. Raised serum CA19-9, bilirubin, CEA, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and tumour MMP9, and low serum albumin were most associated with poorer survival; however, the cutoff values used widely varied. Several promising molecular markers with prognostic significance were also identified, including tumour HMGA2, MUC5AC/6, IDH1, PIWIL2, and DNA index. In conclusion, several biomarkers have been identified in serum and tumour specimens that prognosticate overall and disease-free survival after pCCA resection. These, however, require external validation in large cohort studies and/or in preoperatively obtained specimens, especially tissue biopsy, to recommend their use.

Abstract Aim Pancreatic ductal adenocarcinoma (PDAC) has the lowest survival rate of all major cancers. Chemotherapy is the mainstay systemic therapy for PDAC, and chemoresistance is a major clinical problem leading to therapeutic failure. This study aimed to identify key differences in gene expression profile in tumors from chemoresponsive and chemoresistant patients. Methods Archived formalin‐fixed paraffin‐embedded tumor tissue samples from patients treated with neoadjuvant chemotherapy were obtained during surgical resection. Specimens were macrodissected and gene expression analysis was performed. Multi‐ and univariate statistical analysis was performed to identify differential gene expression profile of tumors from good (0%–30% residual viable tumor [RVT]) and poor (>30% RVT) chemotherapy‐responders. Results Initially, unsupervised multivariate modeling was performed by principal component analysis, which demonstrated a distinct gene expression profile between good‐ and poor‐chemotherapy responders. There were 396 genes that were significantly (p < 0.05) downregulated (200 genes) or upregulated (196 genes) in tumors from good responders compared to poor responders. Further supervised multivariate analysis of significant genes by partial least square (PLS) demonstrated a highly distinct gene expression profile between good‐ and poor responders. A gene biomarker of panel (IL18, SPA17, CD58, PTTG1, MTBP, ABL1, SFRP1, CHRDL1, IGF1, and CFD) was selected based on PLS model, and univariate regression analysis of individual genes was performed. The identified biomarker panel demonstrated a very high ability to diagnose good‐responding PDAC patients (AUROC: 0.977, sensitivity: 82.4%; specificity: 87.0%). Conclusion A distinct tumor biological profile between PDAC patients who either respond or not respond to chemotherapy was identified.

BACKGROUND:Despite its proposed benefits, laparoscopic pancreaticoduodenectomy (LPD) has not been widely adopted due to its technical complexity and steep learning curve. The aim of this study was to report a single surgeon's experience in the stepwise implementation of LPD and evolution of technique over a nine-year period in a moderate-high volume unit.METHODS:Carefully selected patients underwent LPD initially by hybrid approach (laparoscopic resection and open reconstruction), which evolved into a total LPD (laparoscopic resection and reconstruction). Data was prospectively collected to include patient characteristics, intraoperative data, evolution of technique and postoperative outcomes.RESULTS:A total of 25 patients underwent hybrid LPD (HLPD) and 20 patients underwent total LPD (TLPD). There was no 90-day mortality. Three patients developed a postoperative pancreatic fistula (POPF), all of which occurred in patients undergoing HLPD. There was no POPF in 20 consecutive TLPD. There was no evidence of anastomotic strictures in the hepaticojejunostomy in patients undergoing TLPD at long term follow up.CONCLUSION:A gradual and cautious progression from HLPD to TLPD is essential to ensure safe implementation into a unit. LPD should only be considered in carefully selected patients, with outcomes subjected to regular and rigorous independent audit.

BACKGROUND:The diagnosis of postoperative or post-pancreatectomy acute pancreatitis (PPAP) is controversial. In 2021, the International Study Group of Pancreatic Surgery (ISGPS) published the first unifying definition and grading system for PPAP. This study sought to validate recent consensus criteria, using a cohort of patients undergoing pancreaticoduodenectomy (PD) in a high-volume pancreaticobiliary specialty unit. METHODS:All consecutive patients undergoing PD at a tertiary referral centre between January 2016 and December 2021 were retrospectively reviewed. Patients with serum amylase recorded within 48h from surgery were included for analysis. Postoperative data were extracted and evaluated against the ISGPS criteria, including the presence of postoperative hyperamylasaemia, radiologic features consistent with acute pancreatitis, and clinical deterioration. RESULTS:A total of 82 patients were evaluated. The overall incidence of PPAP was 32% (26/82) in this cohort, of which 3/26 demonstrated postoperative hyperamylasaemia and 23/26 had clinically relevant PPAP (Grade B or C) when correlated radiologic and clinical criteria. CONCLUSIONS:This study is among the first to apply the recently published consensus criteria for PPAP diagnosis and grading to clinical data. While the results support their utility in establishing PPAP as a distinct post-pancreatectomy complication, there remains a need for future large-scale validation studies.

Background and aims: Pancreatic resection is associated with pancreatic exocrine insufficiency (PEI) leading to nutritional consequences. The Pancreatic Nutrition Clinic was established to diagnose and manage PEI through standardised nutritional assessment. In this prospective observational study, we aimed to define the rate of PEI, diabetes mellitus and nutritional abnormalities in patients who underwent pancreatic resection. Methods: All Pancreatic Nutrition Clinic patients were included for analysis. Clinical data were prospectively obtained at initial assessment. Biochemical data included micronutrient levels, faecal elastase-1 and haemoglobin A1c. Bone mineral density and nutritional assessment were undertaken. Results: Ninety-eight patients were included. Fifty-nine per cent (58/98) had undergone a pancreatoduodenectomy. Ninety-three patients had a faecal elastase-1 result, 65% (60/93) of which had a faecal elastase-1 less than 200 mg/g of faeces. Seventy-five patients (76%) of the total population required PERT, and thirty-nine (40%) were classified as malnourished using the patient-generated subjective global assessment tool. Seventy-two per cent (70/97) had a biochemical deficiency of one or more micronutrients. Thirty-eight people (39%) had diabetes mellitus. Of the seventy-eight patients with a bone mineral density scan available for analysis, 29% (23/78) had osteoporosis and 49% (38/78) osteopenia. Conclusions: Pancreatic exocrine insufficiency, micronutrient deficiency, bone disease, diabetes mellitus and malnutrition are highly prevalent in patients who have undergone pancreatic resection. (c) 2022 IAP and EPC. Published by Elsevier B.V. All rights reserved.

Background: PuraStat (R) is a non-bioactive haemostatic agent that has demonstrated efficacy in a number of different surgical procedures. We performed a prospective multi-centre post-market study to evaluate the efficacy and safety of PuraStat (R) in liver resections performed for metastatic tumors. Methods: This was a prospective cohort study. Patients undergoing liver resection for metastatic tumor were screened for eligibility, and included if they were >= 18 years old, undergoing open liver resection, had normal liver function, and required application of PuraStat (R) for haemostasis where standard haemostatic techniques were either insufficient or impractical. The primary endpoint was "time to haemostasis" (TTH). Secondary endpoints included blood loss, total postoperative drainage volume, transfusion of blood products, and ease of use. Results: Eighty patients were included for analysis in the intention to treat population. 207 bleeding sites were treated with PuraStat. Of these, 190 (91.7%) bleeding sites reached haemostasis after PuraStat (R) application. Mean TTH (mm:ss) was 1:01 (SD 1:06, range 0:09-6:55). Ease of use of the product was described as either "excellent" or "good" in 78 (98.8%) patients. No serious adverse events were identified. Conclusion: This study confirms the safety, efficacy and ease of use of PuraStat (R) in the management of bleeding in liver surgery.