Donor Blood Tests do Not Predict Pancreas Graft Survival After Simultaneous Pancreas Kidney Transplantation; a National Cohort Study.

Simultaneous pancreas-kidney (SPK) transplantation improves quality of life and limits progression of diabetic complications. There is reluctance to accept pancreata from donors with abnormal blood tests, due to concern of inferior outcomes. We investigated whether donor amylase and liver blood tests (markers of visceral ischaemic injury) predict pancreas graft outcome using the UK Transplant Registry (2016-2021). 857 SPK recipients were included (619 following brainstem death, 238 following circulatory death). Peak donor amylase ranged from 8 to 3300 U/L (median = 70), and this had no impact on pancreas graft survival when adjusting for multiple confounders (aHR = 0.944, 95% CI = 0.754-1.81). Peak alanine transaminases also did not influence pancreas graft survival in multivariable models (aHR = 0.967, 95% CI = 0.848-1.102). Restricted cubic splines were used to assess associations between donor blood tests and pancreas graft survival without assuming linear relationships; these confirmed neither amylase, nor transaminases, significantly impact pancreas transplant outcome. This is the largest, most statistically robust study evaluating donor blood tests and transplant outcome. Provided other factors are acceptable, pancreata from donors with mild or moderately raised amylase and transaminases can be accepted with confidence. The use of pancreas grafts from such donors is therefore a safe, immediate, and simple approach to expand the donor pool to reach increasing demands.

Does Time to Asystole in Donors After Circulatory Death Impact Recipient Outcome in Liver Transplantation?

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.

Liver Transplantation for Nonresectable Colorectal Liver Metastases (CRLM).

Transplantation represents the most radical locoregional therapy through removal of the liver, associated vasculature and locoregional lymph nodes, and replacing it with an allograft. Recent evidence has demonstrated that transplantation for unresectable CRLM is feasible with acceptable post-transplant outcomes in a highly selected cohort of patients. Controversy exists regarding whether transplantation is an appropriate treatment for such patients, due to concerns regarding disease recurrence in the transplanted graft in an immunosuppressed recipient along with utilising a donor liver which are in short supply. Expanding the indications for liver transplantation may also limit access for other patients with end-stage liver disease having ethical implications due to the effect of increasing the waiting list. In this review, we summarise the current evidence for liver transplantation in patients with nonresectable CRLM and highlight unresolved controversies and future directions for this type of treatment.

Surgical management, including the role of transplantation, for intrahepatic and peri-hilar cholangiocarcinoma.

Intrahepatic and peri-hilar cholangiocarcinoma are life threatening disease with poor outcomes despite optimal treatment currently available (5-year overall survival following resection 20-35%, and <10% cured at 10-years post resection). The insidious onset makes diagnosis difficult, the majority do not have a resection option and the high recurrence rate post-resection suggests that occult metastatic disease is frequently present. Advances in perioperative management, such as ipsilateral portal vein (and hepatic vein) embolisation methods to increase the future liver remnant volume, genomic profiling, and (neo)adjuvant therapies demonstrate great potential in improving outcomes. However multiple areas of controversy exist. Surgical resection rate and outcomes vary between centres with no global consensus on how 'resectable' disease is defined - molecular profiling and genomic analysis could potentially identify patients unlikely to benefit from resection or likely to benefit from targeted therapies. FDG-PET scanning has also improved the ability to detect metastatic disease preoperatively and avoid futile resection. However tumours frequently invade major vasculo-biliary structures, with resection and reconstruction associated with significant morbidity and mortality even in specialist centres. Liver transplantation has been investigated for very selected patients for the last decade and yet the selection algorithm, surgical approach and both value of both neoadjuvant and adjuvant therapies remain to be clarified. In this review, we discuss the contemporary management of intrahepatic and peri-hilar cholangiocarcinoma.

The impact of time to death in donors after circulatory death on recipient outcome in simultaneous pancreas-kidney transplantation.

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.

Fibrin-based haemostatic agents for reducing blood loss in adult liver resection.

BACKGROUND: Liver resection is the optimal treatment for selected benign and malignant liver tumours, but it can be associated with significant blood loss. Numerous anaesthetic and surgical techniques have been developed to reduce blood loss and improve perioperative outcomes. One such technique is the application of topical fibrin-based haemostatic agents (FBHAs) to the resection surface. There is no standard practice for FBHA use, and a variety of commercial agents and devices are available, as well as non-FBHAs (e.g. collagen-based agents). The literature is inconclusive on the effectiveness of these methods and on the clinical benefits of their routine use. OBJECTIVES: To evaluate the benefits and harms of fibrin-based haemostatic agents in reducing intraoperative blood loss in adults undergoing liver resection. SEARCH METHODS: We searched the Cochrane Hepato-Biliary Group (CHBG) Controlled Trials Register, CENTRAL, MEDLINE, Embase, LILACS, Science Citation Index Expanded, and Conference Proceedings Citation Index-Science up to 20 January 2023. We also searched online trial registries, checked the reference lists of all primary studies, and contacted the authors of included trials for additional published or unpublished trials. SELECTION CRITERIA: We considered for inclusion all randomised clinical trials evaluating FBHAs versus no topical intervention or non-FBHAs, irrespective of publication type, publication status, language of publication, and outcomes reported. Eligible participants could have any liver pathology and be undergoing major or minor liver resections through open or laparoscopic surgery. DATA COLLECTION AND ANALYSIS: Two review authors independently screened the results of the literature search and used data extraction forms to collate the results. We expressed dichotomous outcome results as risk ratios (RRs) and continuous outcome results as mean differences (MDs), each with their corresponding 95% confidence interval (CI). We used a random-effects model for the main analyses. Our primary outcomes were perioperative mortality, serious adverse events, haemostatic efficacy, and health-related quality of life. Our secondary outcomes were efficacy as sealant, adverse events considered non-serious, operating time, and length of hospital stay. We assessed the certainty of the evidence with GRADE and presented results in two summary of findings tables. MAIN RESULTS: We included 22 trials (2945 participants) evaluating FBHAs versus no intervention or non-FBHAs; 19 trials with 2642 participants provided data for the meta-analyses. Twelve trials reported commercial funding, one trial reported no financial support, and nine trials provided no information on funding. Below we present the most clinically relevant outcome results, also displayed in our summary of findings table. Fibrin-based haemostatic agents versus no intervention Six trials (1001 participants) compared FBHAs with no intervention. One trial was at low risk of bias in all five domains, and all other trials were at high or unclear risk of bias in at least one domain. Two trials were at high risk of bias related to blinding. It is unclear if FBHAs compared with no intervention have an effect on perioperative mortality (RR 2.58, 95% CI 0.89 to 7.44; 4 trials, 782 participants), serious adverse events (RR 0.96, 95% CI 0.88 to 1.05; 4 trials, 782 participants), postoperative transfusion (RR 1.04, 95% CI 0.77 to 1.40; 5 trials, 864 participants), reoperation (RR 2.92, 95% CI 0.58 to 14.61; 2 trials, 612 participants), or postoperative bile leak (RR 1.00, 95% CI 0.67 to 1.48; 4 trials, 782 participants), as the certainty of evidence was very low for all these outcomes. Fibrin-based haemostatic agents versus non-fibrin-based haemostatic agents Sixteen trials (1944 participants) compared FBHAs with non-FBHAs. All trials had at least one domain at high or unclear risk of bias. Twelve trials were at high risk of bias related to blinding. It is unclear if FBHAs compared with non-FBHAs have an effect on perioperative mortality (RR 1.03, 95% CI 0.62 to 1.72; 11 trials, 1436 participants), postoperative transfusion (RR 0.92, 95% CI 0.68 to 1.25; 7 trials, 599 participants), reoperation (RR 0.48, 95% CI 0.25 to 0.90; 3 trials, 358 participants), or postoperative bile leak (RR 1.15, 95% CI 0.60 to 2.21; 9 trials, 1115 participants), as the certainty of evidence was very low for all these outcomes. FBHAs compared with non-FBHAs may have little or no effect on the risk of serious adverse events (RR 0.99, 95% CI 0.95 to 1.03; 9 trials, 1176 participants; low-certainty evidence). AUTHORS' CONCLUSIONS: The evidence for the outcomes in both comparisons (FBHAs versus no intervention and FBHAs versus non-FBHAs) was of very low certainty (or low certainty in one instance) and cannot justify the routine use of FBHAs to reduce blood loss in adult liver resection. While the meta-analysis showed a reduced risk of reoperation with FBHAs compared with non-FBHAs, the analysis was confounded by the small number of trials reporting the event and the risk of bias in all these trials. Future trials should focus on the use of FBHAs in people undergoing liver resection who are at particularly high risk of bleeding. Investigators should evaluate clinically meaningful and patient-important outcomes and follow the SPIRIT and CONSORT statements.

Risk factors for decompensation and death following umbilical hernia repair in patients with end-stage liver disease.

INTRODUCTION: Symptomatic umbilical hernias are a common cause of morbidity and mortality in patients with cirrhosis and end-stage liver disease (ESLD). This study set out to characterise the factors predicting outcome following repair of symptomatic umbilical hernias in ESLD at a single institution. METHODS: A retrospective review was performed of all patients with ESLD who underwent repair of a symptomatic umbilical hernia between 1998 and 2020. Overall survival was predicted using the Kaplan-Meier method. Logistic regression was used to determine predictors of decompensation and 30-day, 90-day and 1-year mortality. RESULTS: One-hundred-and-eight patients with ESLD underwent umbilical hernia repair (emergency n = 78, 72.2%). Transjugular shunting was performed in 29 patients (26.9%). Decompensation occurred in 44 patients (40.7%) and was predicted by emergency surgery (OR, 13.29; P = 0.001). Length of stay was shorter in elective patients compared to emergency patients (3-days vs. 7-days; P = 0.003). Thirty-day, 90-day and 1-year survival was 95.2, 93.2 and 85.4%, respectively. Model for ESLD score >15 predicted 90-day mortality (OR, 18.48; P = 0.030) and hyponatraemia predicted 1-year mortality (OR, 5.31; P = 0.047). Transjugular shunting predicted survival at 1 year (OR, 0.15; P = 0.038). CONCLUSIONS: Repair of symptomatic umbilical hernias in patients with ESLD can be undertaken with acceptable outcomes in a specialist centre, however, this remains a high-risk intervention. Patients undergoing emergency repair are more likely to decompensate postoperatively, develop wound-related problems and have a longer length of stay. Transjugular shunting may confer a benefit to survival, but further prospective trials are warranted.

The Influence of Patients' Age on the Outcome of Treatment for Pancreatic Ductal Adenocarcinoma.

OBJECTIVE: The aim of the study was to determine the impact of age on curative management and outcomes of patients with pancreatic ductal adenocarcinoma. METHODS: Patients who underwent resection for pancreatic ductal adenocarcinoma at 2 units were retrospectively reviewed (between 2005 and 2017) and stratified by age (older patients ≥70 years). Regression analysis was used to explore factors impacting administration of adjuvant chemotherapy and survival. The Kaplan-Meier method was used to estimate overall survival (time from surgery to death). Statistical significance was set at P < 0.05. RESULTS: From 2005 to 2014, 222 patients were identified (<70 years, n = 128; ≥70 years, n = 94). Elderly patients were less likely to receive adjuvant chemotherapy compared with younger patients (odds ratio, 0.57, P = 0.041). Tumor stage, margin, and year of surgery (post-2011 vs pre-2011) were not predictors for chemotherapy receipt (P > 0.05). Frailty was the commonest reason (36.8%) to decline chemotherapy in elderly patients. In patients receiving adjuvant chemotherapy, completion rates (P = 0.32) and overall survival (24 months vs 30 months, P = 0.50) were no different. CONCLUSIONS: Elderly patients demonstrate similar outcomes to younger yet are less likely to commence chemotherapy because of frailty. Holistic preoperative assessment may improve selection for curative treatment.

Impact of Regional Organ Sharing and Allocation in the UK Northern Liver Alliance on Waiting Time to Liver Transplantation and Waitlist Survival.

BACKGROUND: In the United Kingdom, liver transplantation (LT) is undertaken in 7 supraregional centers. Until March 2018, liver grafts were offered to a center and allocated to a patient on their elective waiting list (WL) based on unit prioritization. Patients in Newcastle, Leeds, and Edinburgh with a United Kingdom Model for End-Stage Liver Disease (UKELD) score ≥62 were registered on a common WL and prioritized for deceased-donor liver allocation. This was known as the Northern Liver Alliance (NLA) "top-band scheme." Organs were shared between the 3 centers, with a "payback" scheme ensuring no patient in any center was disadvantaged. We investigated whether the NLA had improved WL survival and waiting time (WT) to transplantation. METHODS: Data for this study were obtained from the UK Transplant Registry maintained by National Health Service Blood and Transplant. This study was based on adult patients registered for first elective liver transplant between April 2013 and December 2016. Non-NLA centers were controls. The Kaplan-Meier method was used to estimate WL survival and median WT to transplant, with the log-rank test used to make comparisons; a Bonferroni correction was applied post hoc to determine pairwise differences. RESULTS: WT was significantly lower at NLA centers compared with non-NLA centers for top-band patients (23 versus 99 days, P < 0.001). However, WL survival was not significantly different for top-band patients (P > 0.999) comparing NLA with non-NLA centers. WL survival for nontop-band patients was no different (P > 0.999) comparing NLA with non-NLA centers. CONCLUSIONS: The NLA achieved its aim, providing earlier transplantation to patients with the greatest need. Nontop-band patients did not experience inferior survival.