BACKGROUND:Minimally invasive left-sided pancreatectomy (MIS-LP) is increasingly adopted for resection of grade 1 and 2 pancreatic neuroendocrine tumours (PNETs), but its oncological equivalence to open left-sided pancreatectomy (O-LP) remains to be fully evaluated. METHODS:We conducted a retrospective cohort study using SEER-Medicare data (2010-2019) including all patients who underwent left-sided pancreatectomy (LP) for PNETs. A multilevel Cox regression model was used to to provide adjusted hazard ratios (HR) for overall survival (OS) and cancer-specific survival (CSS) when comparing between MIS-LP and O-LP. A 6-month landmark survival analysis was performed to account for early postoperative deaths. RESULTS:A total of 772 patients were included, with 257 (33.3%) undergoing MIS-LP. Six-hundred-and-seventy-two patients had grade 1, and 100 patients had grade 2 PNETs. MIS-LP was associated with better OS (HR 0.48, 95% CI 0.26-0.86, P=0.014) and CSS (HR 0.35, 95% CI 0.14-0.88, P=0.026). In the 6-month landmark analysis, O-LP was associated with similar OS and CSS to MIS-LP. CONCLUSION:MIS-LP is associated with improved early survival compared to O-LP in patients with low- to intermediate-grade PNETs.

Background:In circulatory death transplantation, time to death (TTD) following withdrawal of life-sustaining treatment is unpredictable. Concerns persist that prolonged TTD may cause ischemic injury, resulting in organ nonuse. We assessed the impact of donor TTD on liver transplant outcomes and utilization. Methods:We used Organ Procurement and Transplantation Network data on adult donors after circulatory death transplants (2010-2025). Multivariable nonlinear (restricted cubic splines) regression models were used to analyze associations. Simulation studies estimated potential increases in liver acceptance rates. Results:In 8489 recipients, short donor TTD was associated with inferior outcome, contrary to popular belief. Prolonged TTD did not show inferior posttransplant outcomes, irrespective of whether normothermic regional perfusion (NRP) was used. Nonlinear modeling (n = 37 447) revealed a sharp decline in utilization once TTD exceeded just 15 min. Given prolonged TTD did not impact outcomes, these declines represent a missed opportunity for organ use. Simulation studies revealed that if surgeons assess organ offers from patients with TTD of 15-30 min identically to those with TTD <10 min, there would have been a 17.1% (95% confidence interval, 15.0%-19.3%) relative increase in utilization, with potentially better outcomes than current practice. In the setting of NRP, short TTD was associated with increased organ nonuse, potentially because of failed viability criteria in damaged livers. Conclusions:Short TTD was associated with inferior posttransplant outcome, challenging the dogma that shorter is better. Prolonged TTD did not negatively impact posttransplant outcomes, irrespective of NRP use. These findings support expanded use of liver donors with prolonged TTD, especially in the era of NRP and advanced perfusion, where viability assessment provides an additional safeguard.

BACKGROUND:Concerns persist that prolonged time to death (TTD) following withdrawal of life-sustaining treatment may impair organ quality. Although previous European studies have demonstrated that prolonged TTD does not impact post-transplant kidney graft survival, it remains unclear whether these findings apply to the US donor pool. METHODS:We used OPTN data on adult DCD single-kidney transplants (2010-2023). Multiple imputation was used for missing data. Multivariable regression models, with restricted cubic splines for non-linear modelling, were used to evaluate the impact of donor TTD on kidney transplant outcomes. RESULTS:Median donor TTD was 14 min (IQR, 10-21 min). Donor TTD was not associated with recipient graft survival (p = 0.469), mortality (p = 0.528) or 1-year eGFR (p = 0.393). These findings were consistent regardless of normothermic regional perfusion use (NRP cohort: n = 1227; non-NRP cohort: n = 35 328), and within the large ex-situ hypothermic machine perfusion cohort (HMP- cohort: n = 22 218). Only 4.1% of transplanted DCD kidneys were from donors with TTD of over 60 min, and just 0.1% exceeded 120 min. CONCLUSIONS:Increasing donor TTD was not associated with worse post-kidney-transplant outcomes within this cohort predominantly comprising donors with TTD 0-60 min. In contrast to this US setting, a previous UK study reported that a higher proportion of transplanted DCD kidneys were from prolonged TTD donors (12.3% from donors TTD >60 min; 4.2% from >120 min). This highlights an opportunity to safely expand the US DCD donor pool, especially in the era of machine perfusion where viability assessment may provide an additional safeguard.

Background: Surgical interventions are complex and comprise multiple components, creating difficulties when considering how they might be described, standardised, and monitored (i.e., quality assurance) within randomised controlled trials (RCTs). Consolidated Standards of Reporting Trials - Non-Pharmacological Treatment (CONSORT-NPT) provides specific recommendations to improve the quality, transparency, and replicability of RCTs involving a surgical intervention. This structured narrative review explores and summarizes the reporting of quality assurance measures for surgical interventions in RCTs, using pancreatoduodenectomy (PD) as an exploratory case study. Methods: Searches for RCTs of PD were undertaken in PubMed, Medline, the Cochrane Central Register of Controlled Trials, and the Cochrane Database of Systematic Reviews from 2020 to 2024. Pancreatoduodenectomy (PD) was deconstructed into its constituent components (n = 40), and selected RCTs were scrutinised to explore reporting of quality assurance measures against the deconstructed components as described in CONSORT-NPT. Results: Of 189 screened articles, 37 RCTs were included, reporting on 5659 patients across 16 countries. No studies described all components of PD, and four did not report any components at all. Nine studies described some form of standardisation, and three measured adherence to standards, using intra-operative photographs. Minimum surgeon and centre volumes were specified in two and six trials, respectively. Conclusions: Quality assurance measures were poorly reported in selected RCTs involving PD, creating uncertainty in interpreting results. To enhance the design of future RCTs, a wider consensus regarding the core components of a PD is required. This will facilitate subsequent consideration of how these might need to be reported in future pancreatic surgical RCTs.

BACKGROUND:Machine perfusion technology has redefined donor and recipient criteria for liver transplantation. Despite increasing adoption, data regarding graft and recipient factors associated with unsuccessful normothermic machine perfusion (NMP) outcomes remain limited. METHODS:The Organ Procurement and Transplantation Network database was used to retrospectively identify adult patients undergoing deceased donor liver transplantation with NMP preservation between January 10, 2021, and December 31, 2024. Populations were stratified by 1-year graft status, with donor and recipient factors compared. Logistic regression identified factors independently associated with NMP graft failure, and center analyses assessed program-level impacts. RESULTS:Among 4928 NMP cases, 398 (8.1%) experienced 1-year graft failure. They were more frequently admitted to the intensive care unit (ICU) at transplant (21.1% vs. 10.6%, p < 0.001) and had more complex abdominal histories, including higher rates of TIPS(17.0% vs. 12.0%), prior abdominal surgery (64.1% vs. 54.7%), and prior liver transplant (10.3% vs. 3.4%) (all p < 0.01). Regression analysis identified increased odds of graft failure with MELD score 35 (aOR 2.10 [1.21-3.63]), low recipient functional status (aOR 2.05 [1.31-3.21]), and prior abdominal surgery (aOR 1.33 [1.01-1.76]). Alcohol-associated liver disease (aOR 0.36 [0.23-0.56]) was the only factor conferring a protective effect. Centers with higher-than-expected standardized NMP graft failure rates were higher-volume programs with low-risk case mixes; no centers had persistently high standardized failure rates throughout the study period. CONCLUSION:Recipient factors, particularly those conferring surgical complexity, are more significantly associated with NMP graft failure than donor factors. Despite increased adoption of perfusion technologies to mitigate donor and operative risk, transplant provider clinical judgment remains critical for optimizing recipient-donor matching and outcomes.

Candidates awaiting liver transplantation may undergo waitlist suspension, the temporary inactivation of candidates from organ allocation, for various medical or logistical reasons. We performed a national cohort study using the United Kingdom Transplant Registry to evaluate the association between waitlist suspension and outcomes in adults listed for liver-only transplantation. Adjusted time-varying cause-specific Cox models, with start-stop times for suspension, were used as the primary analysis. Separate sensitivity analyses adjusted for center-specific effects, censoring for COVID-19-related suspensions, censoring clinical improvement suspensions, and incorporating a 30-day landmark removing early events from the risk set. Among 13 596 candidates, 3250 (23.9%) experienced at least 1 suspension episode. In adjusted time-varying analyses, reactivation following suspension was strongly associated with reduced access to transplantation (hazard ratio [HR], 0.36; 95% confidence interval [CI], 0.32-0.39, P < .001), but was not associated with increased death/delisting hazard (HR, 0.95; 95% CI, 0.84-1.08, P = .451), and currently suspended status showed no consistent association with death/delisting (HR, 1.11; 95% CI, 0.90-1.37, P = .310). Findings were robust across center-adjustment and sensitivity analyses. Waitlist suspension identifies a clinically important transition point after which transplant access remains reduced despite reactivation.

BACKGROUND:Robotic left-sided pancreatectomy is increasingly adopted worldwide, yet the impact of the learning curve on clinical and oncological outcomes remains unclear. The Brescia consensus defines the first 21 cases as the competency phase, but real-world validation is limited. We evaluated whether the surgical learning phase influenced major morbidity and oncological quality following robotic left-sided pancreatectomy. METHODS:This multicenter retrospective cohort study included consecutive patients undergoing robotic left-sided pancreatectomy across 10 high-volume centers in the United Kingdom, Europe, United States, and Australia (2014-2025). The learning phase was categorized as competency (cases 1-21) or proficiency (>21). The primary endpoint was major morbidity (Clavien-Dindo ≥IIIa). Mixed-effects logistic regression, restricted cubic splines, and risk-adjusted cumulative sum analyses evaluated predictors of morbidity and center-level performance. In the pancreatic ductal adenocarcinoma subgroup, factors associated with R1 margins were assessed. RESULTS:Among 521 patients, 200 (38.4%) were in the competency and 321 (61.6%) in the proficiency phase. Major morbidity was comparable between phases (14.5% vs 14.0%; P = .981). Independent predictors of major morbidity included male sex (odds ratio, 1.76; P = .037), preoperative pancreatitis (odds ratio, 2.23, P = .031), and multivisceral resection (odds ratio, 2.29; P = .034). In the pancreatic ductal adenocarcinoma subgroup (n = 110), R1 rates were higher in the proficiency phase but nonsignificant (39.7% vs 21.6%; P = .092). Increasing operative time (odds ratio, 1.39/h; P = .004) and node-positive disease (odds ratio, 2.62; P = .047) predicted R1 resection. Spline and risk-adjusted cumulative sum analyses showed no early excess harm. CONCLUSION:Robotic left-sided pancreatectomy can be safely adopted within structured programs without increased early morbidity. However, evolving case complexity during the proficiency phase necessitates ongoing oncological vigilance and robust institutional oversight.

The impact of HLA mismatch and induction therapy in simultaneous pancreas-kidney transplantation on outcomes remains incompletely defined. We conducted a retrospective cohort study of 1705 SPK recipients transplanted in the UK between 2007 and 2019. Using national transplant registry data, we analysed the impact of locus-specific HLA mismatch and induction therapy (Alemtuzumab vs. Basiliximab) on pancreas graft survival primarily. Kidney graft and patient survival were also analysed as secondary outcomes. Multivariable Cox proportional hazards models were adjusted for donor, recipient, and transplant variables. Pancreas graft survival at 1- and 10-year post-transplant was estimated to be 88.6% and 72.7%, respectively. Kidney graft and patient survival at 10 years were 76.7% and 75.3%. In adjusted analyses, donor age, cold ischaemic time, and HLA-DQ mismatch were significantly associated with pancreas graft loss. No significant survival difference was seen between Alemtuzumab and Basiliximab induction therapy. Induction therapy and HLA-mismatch status were not associated with pancreas graft outcome in this large registry study.

Background: Recent Brescia guidelines suggest proficiency in robotic left-sided pancreatectomy (RLP) occurs after the first 21 cases (competency phase). This study reports textbook outcome (TO) rates in the competency and proficiency phases following RLP, and predictors of achieving TO. Methods: A retrospective cohort study of all RLP procedures from six UK centres was undertaken from July 2014 to August 2024. TO was defined as a composite of hospital length of stay, major morbidity, in-hospital mortality, 90-day readmission, and clinically relevant postoperative pancreatic fistula (CR-POPF). Multivariable logistic regression analysis was used to model predictors of TO. Results: In all, 281 patients underwent RLP. The median number of laparoscopic left-sided pancreatectomies undertaken before starting the RLP programme was 70 (interquartile range 40-175) per centre. In all, 109 patients underwent RLP in the competency phase and 172 underwent RLP in the proficiency phase; TO was achieved in 57 patients (52.3%) and 86 patients (50.0%), respectively (P = 0.801). Major morbidity occurred in 38 patients (13.5%), 68 patients were readmitted within 90 days (24.2%), and 57 patients had CR-POPF (20.3%). Patients in the proficiency phase had a longer operating time (315 versus 230 minutes; P < 0.0001), a lower rate of splenic preservation (23 versus 27; P = 0.023), and a lower rate of vascular infiltration (12 versus 22; P = 0.002) than patients in the competency phase. TO was less likely with a prolonged operation time (odds ratio 0.82 per hour; 95% c.i. 0.70 to 0.95; P = 0.010) with a non-linear trend noted. Conclusion: TO after RLP was achieved in half the resected patients in this UK series. There was no difference in the TO rate between the competency and proficiency phases, and previous experience with laparoscopic left-sided pancreatectomy may have contributed to this.

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide. Curative-intent treatments offer the best long-term outcomes for selected patients. However, recurrence rates after resection approach 70

Abstract Introduction Simultaneous pancreas-kidney (SPK) transplantation improves quality of life in people with diabetes and end-stage renal disease, and limits the progression of diabetes related complications. Many surgeons are reluctant to accept the pancreas of a donor with raised amylase, due to concern of potentially inferior outcomes. We aim to ascertain whether donor amylase and liver blood tests (a marker of visceral ischaemic injury) predict pancreas transplant outcome. Methods This retrospective cohort study used the NHS registry on adult SPK transplantation (2016-2021). Adjusted regressions models assessed the effect of donor amylase and liver blood tests on pancreas transplant outcome. Results 857 SPK recipients were included (619 following brainstem death, 238 following circulatory death). Peak donor amylase ranged from 8-3300U/L (median=70). Donor peak amylase had no significant impact on pancreas graft survival when adjusting for multiple confounders (aHR=0.944, 95% CI=0.754-1.81). Median peak alanine transaminase and aspartate transaminase was 67U/L and 72U/L (range 8-5930 and 0-7910U/L). Neither of these influenced pancreas graft survival in multivariable models (aHR=0.967, 95% CI=0.848-1.102 and aHR=0.908, 95% CI=0.771-1.070, respectively). Restricted cubic splines were used to assess the relationship between donor blood tests and pancreas graft survival without assuming linear relationships; these confirmed neither amylase, nor transaminases, significantly impact on pancreas transplant outcome. Conclusions Donor amylase and transaminases do not predict transplant outcomes. Therefore, raised donor amylase or transaminases should not be considered a barrier to organ utilisation. The use of pancreas grafts from donors with hyperamylasaemia is a safe, immediate, and simple approach to expand the donor pool.

Abstract Background Liver transplantation is limited by the number of optimal organs for transplantation. Ischaemia reperfusion injury (IRI) plays a key role in the utilisation of organs for transplantation - many organs are still not used due to concerns over viability. We evaluated the C5 inhibitor Eculizumab (EZB) in a cell model of IRI. Methods HepG2 cells, an immortalised hepatocyte cell-line, were utilised to model IRI. Cells were incubated in an anoxic chamber to model 'ischaemia' and then 'reperfused' in a normoxic incubator for 4 and 1 hours, respectively. The incubation media was supplemented with perfusate from donation after circulatory death (DCD) livers that had undergone standard normothermic machine perfusion (n=2) and EZB treated perfusate (n=2). Results The IRI model reduced cell viability and proliferation (p≤0.05). However, the model created no significant changes in the production of biomarkers VEGF, IL-10, IL-8, GDF-15 and ROS (p>0.05). Notably, EZB therapy significantly increased anti-inflammatory IL-10 production (p≤0.0001) and expression (p≤0.001), whilst enhancing cell viability and proliferation (p≤0.0001). Conclusion The complement system may play an important role within IRI and complement inhibition is a promising treatment for DCD livers, as demonstrated by treatment of cells with EZB therapy. Further work is required to optimise the models and treatment strategy before clinical testing.

Background. The agonal phase can vary following treatment withdrawal in donor after circulatory death (DCD). There is little evidence to support when procurement teams should stand down in relation to donor time to death (TTD). We assessed what impact TTD had on outcomes following DCD liver transplantation. Methods. Data were extracted from the UK Transplant Registry on DCD liver transplant recipients from 2006 to 2021. TTD was the time from withdrawal of life-sustaining treatment to asystole, and functional warm ischemia time was the time from donor systolic blood pressure and/or oxygen saturation falling below 50 mm Hg and 70%, respectively, to aortic perfusion. The primary endpoint was 1-y graft survival. Potential predictors were fitted into Cox proportional hazards models. Adjusted restricted cubic spline models were generated to further delineate the relationship between TTD and outcome. Results. One thousand five hundred fifty-eight recipients of a DCD liver graft were included. Median TTD in the entire cohort was 13 min (interquartile range, 9–17 min). Restricted cubic splines revealed that the risk of graft loss was significantly greater when TTD ≤14 min. After 14 min, there was no impact on graft loss. Prolonged hepatectomy time was significantly associated with graft loss (hazard ratio, 1.87; 95% confidence interval, 1.23-2.83; P = 0.003); however, functional warm ischemia time had no impact (hazard ratio, 1.00; 95% confidence interval, 0.44-2.27; P > 0.9). Conclusions. A very short TTD was associated with increased risk of graft loss, possibly because of such donors being more unstable and/or experiencing brain stem death as well as circulatory death. Expanding the stand down times may increase the utilization of donor livers without significantly impairing graft outcome.

The time to arrest donors after circulatory death is unpredictable and can vary. This leads to variable periods of warm ischemic damage prior to pancreas transplantation. There is little evidence supporting procurement team stand-down times based on donor time to death (TTD). We examined what impact TTD had on pancreas graft outcomes following donors after circulatory death (DCD) simultaneous pancreas-kidney transplantation. Data were extracted from the UK transplant registry from 2014 to 2022. Predictors of graft loss were evaluated using a Cox proportional hazards model. Adjusted restricted cubic spline models were generated to further delineate the relationship between TTD and outcome. Three-hundred-and-seventy-five DCD simultaneous kidney-pancreas transplant recipients were included. Increasing TTD was not associated with graft survival (adjusted hazard ratio HR 0.98, 95% confidence interval 0.68-1.41, P = .901). Increasing asystolic time worsened graft survival (adjusted hazard ratio 2.51, 95% confidence interval 1.16-5.43, P = .020). Restricted cubic spline modeling revealed a nonlinear relationship between asystolic time and graft survival and no relationship between TTD and graft survival. We found no evidence that TTD impacts pancreas graft survival after DCD simultaneous pancreas-kidney transplantation; however, increasing asystolic time was a significant predictor of graft loss. Procurement teams should attempt to minimize asystolic time to optimize pancreas graft survival rather than focus on the duration of TTD.

Abstract Background Pancreatoduodenectomy (PD) is a complex surgical intervention comprising multiple components which, when delivered differently, can impact outcomes, introduce bias into randomised controlled trials (RCTs) and impair accurate interpretation of results. This study aimed to systematically explore and summarise variation in PD description and standardisation amongst contemporary RCTs in pancreas surgery. Methods Systematic literature searches for RCTs of PD were undertaken from 2020 to 2023. RCTs including robotic PD, or other types of pancreas resection (e.g. total, distal), were excluded. The technical aspects of PD were deconstructed into constituent components and steps (pre-operative considerations, before skin incision, incision, dissection, resection, haemostasis, reconstruction, insertion of adjuncts, closure and after closure) using a methodological framework. Trial reports and protocols were scrutinised to examine whether the components/steps were described, and whether (and how) adherence was assessed. Results Of 83 screened articles, 29 RCTs were included, reporting on 3440 patients across 16 countries (1 trial compared pre-operative interventions, 18 trials compared intra-operative interventions, and 10 trials compared post-operative interventions). Forty-one PD steps were identified. No studies described all steps and five did not describe any. Fifteen component parts were described in one RCT. Only three RCTs reported that delivery of PD was recorded and assessed, using intra-operative photographs in all cases. Conclusions In a contemporary series of RCTs evaluating PD, descriptions of the procedure were inadequate. Clear descriptions of PD using pre-existing methodological frameworks in future trials are warranted to improve outcomes, decrease bias and facilitate cross-RCT comparisons in systematic reviews.

Abstract Background Liver transplantation is the definitive procedure for end-stage liver failure but is limited by a shortage of viable donor organs. IRI is an unavoidable consequence of transplantation, triggering damage via several pathways, including complement activation. Development of an in vitro cell model of IRI with addition of complement allows analysis of cholangiocyte cellular stress response and whether this response can be attenuated by eculizumab, a complement inhibitor. Methods H69 cholangiocytes were subject to anoxic incubation for 4 hours and subsequent normoxia for 24 hours, before addition of complement to the system. Complement was provided from perfusate taken from liver normothermic machine perfusion (NMP). Analysis of cellular response was then carried out at different stages of simulated IRI. Results Eculizumab-treated perfusate significantly increased cell proliferation compared to untreated perfusate (p<0.0001). Addition of complement to the model increased cellular oxidative stress and inflammation. Eculizumab-treated perfusate significantly decreased production of GDF15 (p<0.0001), an oxidative stress marker, in cholangiocytes. Despite a significant increase, compared to the normoxic control, IL-10 and IL-8 production showed no significant difference between cells treated with control NMP perfusate or eculizumab-treated perfusate. VEGF gene expression was upregulated in the context of eculizumab-treated perfusate. Conclusion The in vitro model successfully simulates IRI and addition of perfusate leads to increased production of markers of inflammation and oxidative stress. Complement-depleted perfusate significantly reduced GDF15 production, suggesting amelioration of cellular oxidative stress, by eculizumab; however, we cannot conclude with the current data that complement-depleted perfusate attenuates the effects of IRI in this model.