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BACKGROUND AND METHODS: Treatment strategies for pancreatic cancer patients are made by a multidisciplinary team (MDT) board. We aimed to assess intra-observer variance at MDT boards. Participating units staged, assessed resectability, and made treatment allocations for the same patients as they did two years earlier. We disseminated clinical information and CT images of pancreatic cancer patients judged by one MDT board to have nonmetastatic pancreatic cancer to the participating units. All units were asked to re-assess the TNM stage, resectability, and treatment allocation for each patient. To assess intra-observer variance, we computed %-agreements for each participating unit, defined as low (75%) agreement.RESULTS: Eighteen patients were re-assessed by six MDT boards. The overall agreement was moderate for TNM-stage (ranging from 50%-70%) and resectability assessment (53%) but low for treatment allocation (46%). Agreement on resectability assessments was low to moderate. Findings were similar but more pronounced for treatment allocation. We observed a shift in treatment strategy towards increasing use of neoadjuvant chemotherapy, particularly in patients with borderline resectable and locally advanced tumors.CONCLUSIONS: We found substantial intra-observer agreement variations across six different MDT boards of 18 pancreatic cancer patients with two years between the first and second assessment.

Background and aimsThe incidence of acute pancreatitis (AP) is increasing in the UK. Patients with severe AP require a significant amount of resources to support them during their admission. The ability to predict which patients will develop multiorgan dysfunction remains poor leading to a delay in the identification of these patients and a window of opportunity for early intervention is missed. Social deprivation has been linked with increased mortality across surgical specialties. Its role in predicting mortality in patients with AP remains unclear but would allow high-risk patients to be identified early and to focus resources on high-risk populations.MethodsA prospectively collected single-centre database was analysed. English Index of Multiple Deprivation (IMD) was calculated based on postcode. Patients were grouped according to their English IMD quintile. Outcomes measured included all-cause mortality, Intestive care unit (ITU) admission, overall length of stay (LOS) and local pancreatitis-specific complications.Results398 patients with AP between 2018 and 2021 were identified. There were significantly more patients with AP in Q1 (IMD 1–2) compared with Q5 (IMD 9–10) (156 vs 38, p0.001). In multivariate modelling, there was no significance difference in pancreatitis-related complications, number of ITU visits, number of organs supported and overall, LOS by IMD quintile.ConclusionsAlthough there was a significantly higher number of patients admitted to our unit with AP from the most socially deprived quintiles, there was no correlation between social economic deprivation and mortality following AP.

Introduction and objectives Graft failure and postoperative mortality are the most serious complications after liver transplantation. The aim of this study is to establish a prognostic scoring system to predict graft and patient survival based on serum transaminases levels that are routinely used during the postoperative period in human cadaveric liver transplants. Patients and methods Postoperative graft failure and patient mortality after liver transplant were analyzed from a consecutive series of 1299 patients undergoing cadaveric liver transplantation. This was correlated with serum liver function tests and the rate of reduction in transaminase levels over the first postoperative week. A cut-off transaminase level correlating with graft and patient survival was calculated and incorporated into a scoring system. Results Aspartate-aminotransferase (AST) on postoperative day one showed significant correlation with early graft failure for levels above 723 U/dl and early postoperative mortality for levels above 750 U/dl. AST reduction rate (day 1 to 3) greater than 1.8 correlated with reduced graft failure and greater than 2 with mortality. Alanine-aminotransferase (ALT) reduction in the first 48 h post transplantation also correlated with outcomes. Conclusion A scoring system with these three variables allowed us to classify our patients into three groups of risk for early graft failure and mortality.

Post-mastectomy radiation therapy (PMRT) is known to increase the complication rate and implant loss in implant-based breast reconstruction. The purpose of this study was to systematically review the literature regarding the outcome of PMRT delivered to the permanent/definitive implant.Systematic review and meta-analysis of studies involving immediate implant-based reconstruction and PMRT when delivered to the permanent implant.Seven studies included 2921 patients (520 PMRT, 2401 control). PMRT was associated with significant increase in capsular contracture (7 studies, 2529 patients, 494 PMRT, 2035 control, OR 10.21, 95% CI 3.74 to 27.89, p 0.00001). In addition, PMRT was associated with a significant increase in revisional surgery (7 studies, 2921 patients, 520 PMRT, 2401 control, OR 2.18, 95% CI 1.33 to 3.57, p = 0.002) and reconstructive failure (6 studies, 2814 patients, 496 PMRT, 2318 control, OR 2.52, 95% CI 1.48 to 4.29, p+0.0007). Moreover, it was associated with a significant reduction in patient satisfaction (4 studies, 468 patients, 138 PMRT, 294 control, OR 0.29, 95% CI 0.15 to 0.57, p = 0.0003) and cosmetic outcome (4 studies, 1317 patients, 238 PMRT, 1009 control, OR 28, 95% CI. 0.11 to 0.67, p = 0.005).This meta-analysis demonstrates that within the first 5 years, post implant-based reconstruction for those patients who receive PMRT, the rates of adverse events are increased, and there is a significant reduction in patient satisfaction and cosmetic outcome.

Background Ischaemia Reperfusion (IR) injury is a major cause of morbidity, mortality and graft loss following Orthotopic Liver Transplantation (OLT). Utilising marginal grafts, which are more susceptible to IR injury, makes this a key research goal. Remote Ischaemic Preconditioning (RIPC) has been shown to ameliorate hepatic IR injury in experimental models. Whether RIPC can reduce IR injury in human liver transplant recipients is unknown. Methods Forty patients undergoing liver transplantation were randomized to RIPC or a sham. RIPC was induced through three 5 min cycles of alternate ischaemia and reperfusion of the left leg prior to surgery. Data on clinical outcomes was collected prospectively. Per-operative cytokine levels were measured. Results Fourty five of 51 patients approached (88%) were willing to enroll in the study. Five patients were excluded and 40 randomized, of which 20 underwent RIPC which was successfully completed in all patients. There were no complications following RIPC. Median day 3 AST levels were slightly higher in the RIPC group (221 IU vs 149 IU, p = 1.00). Conclusions RIPC is acceptable and safe in liver transplant recipients. This study has not demonstrated evidence of a reduction in short-term measures of IR injury. Longer follow up will be required and consideration of an altered protocol.

Background Liver resection produces excellent long-term survival for patients with colorectal liver metastases but is associated with significant morbidity and mortality from ischaemia reperfusion injury (IRI). Remote ischaemic preconditioning (RIPC) can reduce the effect of IRI. This pilot randomised controlled trial evaluated RIPC in patients undergoing major hepatectomy at the Royal Free Hospital, London. Methods Sixteen patients were randomised to RIPC or sham control. RIPC was induced through three 10-min cycles of alternate ischaemia and reperfusion to the leg. At baseline and immediately post-resection, transaminases and indocyanine green (ICG) clearance were measured. Findings The RIPC group had lower ALT and AST levels immediately post-resection (ALT: 43% lower 497 ± 165 vs 889 ± 170 IU/L; p = 0.019 AST: 54% lower 408 ± 166 vs 836 ± 167 IU/L; p = 0.001) and at 24 h (ALT: 41% lower 412 ± 144 vs 698 ± 137 IU/L; p = 0.026 AST: 50% lower 316 ± 116 vs 668 ± 115 IU/L; p = 0.02). ICG clearance was reduced in controls versus RIPC immediately after resection (ICG-PDR: 11.1 ± 1.1 vs 16.5 ± 1.4%/min; p = 0.035). Conclusions This pilot study shows that RIPC has potential to reduce liver injury following hepatectomy justifying a prospective RCT powered to demonstrate clinical benefits.

Ischaemic preconditioning (IPC) is a strategy to reduce ischaemia-reperfusion (IR) injury. Its benefit in human liver transplantation is unclear. The aim of this study was to analyse the current evidence for donor IPC in liver transplantation. Systematic review and meta-analysis of studies involving IPC of liver transplant donors. Ovid Medline, Embase and Cochrane CENTRAL were searched up until January 2015. Data retrieved included the primary outcomes of 1-year mortality, incidence of primary graft non-function (PGNF) and retransplantation. Secondary outcomes included aspartate aminotransferase (AST) levels on day 3 post-op. Pooled odds ratios (ORs) were calculated for dichotomous data and mean weighted ratios for continuous data. Ten studies included 593 patients (286 IPC; 307 control). IPC was associated with a reduction in mortality at 1 year (6% vs. 11%) although this was not statistically significant (OR 0.54, 95% C.I. 0.28-1.04, P = 0.06). The IPC group had a significantly lower day 3 AST level (WMD -66.41iU, P = 0.04). This meta-analysis demonstrates that IPC reduces liver injury following transplantation and produces a large reduction in 1-year mortality which was not statistically significant. Confirmation of clinical benefit from IPC requires an adequately powered prospective RCT.

Background/Objectives: Soluble CD163 (sCD163), a macrophage activation marker, is upregulated in conditions of macrophage proliferation and activation. Elevated sCD163 levels have been associated with liver disease severity and progression. During liver transplantation, the implanted liver is exposed to ischaemia and reperfusion injury, resulting in an acute inflammatory response and macrophage activation. The relationship between sCD163 levels during liver transplantation and the development of early allograft dysfunction (EAD) has not been investigated. Methods: We included 27 cirrhosis patients (age 55 [range 32–72] years, 23 men) on the waiting list for liver transplantation. Alcohol consumption and viral hepatitis were the most frequent causes for cirrhosis. Patients were characterised by standard biochemical analysis and based on clinical disease severity scores. Information about donor, graft and course of the liver transplantation was recorded. sCD163 levels were measured at the time of liver transplantation before surgery, 2 h after reperfusion, and then at 24 h after transplantation. Results: We observed above-normal sCD163 levels at baseline (5.9 mg/L [4.7–8.8]). Two hours after reperfusion, sCD163 levels increased significantly from baseline (8.4 mg/L [7.4–10.9]; P < 0.01). Twenty-four hours after transplantation, sCD163 levels were significantly reduced compared with baseline (3.7 mg/L [2.9–5.5]; P < 0.01). However, in patients with EAD (n = 16), sCD163 levels were increased compared with patients without EAD (4.1 [3.2–7.4] vs. 3.1 [2.8–3.8] mg/L; P = 0.03). Conclusions: We observed elevated sCD163 levels in patients with EAD after liver transplantation, confirming macrophage activation to play a role in EAD. Thus, sCD163 may be used as an early marker for EAD after liver transplantation, but larger studies are warranted to validate these findings.

Background Acute Kidney Injury, a common complication of liver transplant, is associated with a significant increase in the risk of morbidity, mortality and graft loss. Current diagnostic criteria leaves a delay in diagnosis allowing further potential irreversible damage. Early biomarkers of renal injury are of clinical importance and Neutrophil Gelatinase Associated Lipocalins (NGALs) and Syndecan-1 were investigated. Methods AKI was defined according to the Acute Kidney Injury Network criteria. Urine and blood samples were collected pre-operatively, immediately post-op and 24 h post reperfusion to allow measurement of NGAL and Syndecan-1 levels. Results 13 of 27 patients developed an AKI. Patients who developed AKI had significantly higher peak transaminases. Urinary NGAL, plasma NGAL and Syndecan-1 levels were significantly elevated in all patients post reperfusion. Urinary NGAL levels immediately post-op were significantly higher in patients who developed an AKI than those that didn't [1319 ng/ml vs 46.56 ng/ml, p ≤ 0.001]. ROC curves were performed and urinary NGAL levels immediately post-op were an excellent biomarker for AKI with an area under the curve of 0.948 (0.847–1.00). Conclusions Urinary NGAL levels measured immediately post-op accurately predict the development of AKI and their incorporation into clinical practise could allow early protocols to be developed to treat post transplant AKI.

Background Acute kidney injury (AKI) is common after orthotopic liver transplantation (OLT) usually occurring early post-transplant. Multiple causes include graft preservation injury, blood loss, hypotension but also severity of recipient liver disease. Early intervention in AKI has both short and long term patient benefits. Unfortunately there are no current clinical biomarkers of early AKI. Aim To assess the value of NGAL in predicting AKI following OLT. Methods Ovid MEDLINE and EMBASE were searched between the years of 2000 and 2017 for studies using keywords: Neutrophil Gelatinase Associated Lipocalin or NGAL variants combined with synonyms for liver transplantation. Results 96 studies were identified. 11 studies including 563 patients were considered suitable for analysis. Both urinary (uNGAL) and plasma NGAL (pNGAL) measurement were found to predict AKI after liver transplantation. Optimal reported area under the receiver-operator characteristics curve (AUROC) values of 0.5–0.83 and 0.54–0.86 respectively. Conclusions NGAL is a good predictor of early AKI post OLT although there is considerable variation in the published results. Further studies with prospectively defined cut-off values, standardized definitions of AKI and rigorous data reporting should be conducted to establish its clinical usefulness and limitations.

Liver Ischaemia Reperfusion (IR) injury is a major cause of post-operative liver dysfunction, morbidity and mortality following liver resection surgery and transplantation. There are no proven therapies for IR injury in clinical practice and new approaches are required. Ischaemic Preconditioning (IPC) can be applied in both a direct and remote fashion and has been shown to ameliorate IR injury in small animal models. Its translation into clinical practice has been difficult, primarily by a lack of knowledge regarding the dominant protective mechanisms that it employs. A review of all current studies would suggest that IPC/RIPC relies on creating a small tissue injury resulting in the release of adenosine and l-arginine which act through the Adenosine receptors and the haem-oxygenase and endothelial nitric oxide synthase systems to reduce hepatocyte necrosis and improve the hepatic microcirculation post reperfusion. The next key step is to determine how long the stimulus requires to precondition humans to allow sufficient injury to occur to release the potential mediators. This would open the door to a new therapeutic chapter in this field.

Background Ischaemia reperfusion injury is a key cause of mortality and graft loss after liver transplantation. After tissue injury, monocytes are rapidly mobilised and recruited to injured tissue by monocyte chemoattractant protein-1 (MCP-1). Elevated MCP-1 concentrations correlate with poorer outcomes in patients after haemorrhagic stroke but have not been evaluated as a prognostic marker in clinical liver transplantation. We aimed to assess the role of inflammatory monocytes and MCP-1 in ischaemia reperfusion injury Methods Adult patients undergoing liver transplantation at the Royal Free Hospital, London, UK, were recruited. Liver biopsy samples were collected preimplantation and 2 h after reperfusion from five patients. Intrahepatic mononuclear cells were extracted for immediate analysis by flow cytometery. Plasma MCP-1 concentrations from 33 patients were measured preoperatively by ELISA, 2 h and 24 h after reperfusion, and correlated with graft function by measurement of day 3 aspartate aminotransferase (AST) and early allograft dysfunction (EAD) score. Findings Flow cytometric analysis demonstrated an increase in mean classical monocytes after reperfusion compared with preimplantation (4·18% of total live cells [SD 2·61] vs 0·61 [0·38], p=0·018). In three of the five recipients we distinguished cells of donor versus recipient origin by HLA-A allele expression to demonstrate that 88% (6·24) of the classical monocytes were recipient derived in the postreperfusion biopsy sample. Median MCP-1 concentrations were significantly raised after reperfusion (385·61 pg/mL [IQR 244·75–715·20] vs 71·2 [55·61–113·99], p vs 47·44 [29·53–77·73], p=0·037). MCP-1 concentrations at 24 h correlated with day 3 AST concentrations (p=0·002). Interpretation Our results show that classical monocytes are rapidly recruited to the liver after ischaemia reperfusion injury, and that high MCP-1 concentrations at 24 h are associated with poorer graft function. Therefore, MCP-1 blockade presents an attractive strategy to reduce graft ischaemia reperfusion injury. Funding None.

Ischaemic reperfusion (IR) injury is a major cause of graft loss, morbidity and mortality following orthotopic liver transplantation (OLT). Demand for liver transplantation has resulted in increasing use of marginal grafts that are more prone to IR injury. Remote ischaemic preconditioning (RIPC) reduces IR injury in experimental models, but recipient RIPC has not been evaluated clinically. Methods A single-centre double-blind randomized controlled trial (RCT) is planned to test the hypothesis that recipient RIPC will reduce IR injury. RIPC will be performed following recipient anaesthetic induction but prior to skin incision. The protocol involves 3 cycles of 5 min of lower limb occlusion with a pneumatic tourniquet inflated to 200 mmHg alternating with 5 min of reperfusion. In the control group, the sham will involve the cuff being placed on the thigh but without being inflated. The primary endpoint is ability to recruit patients to the trial and safety of RIPC. The key secondary endpoint is a reduction in serum aspartate transferase levels on the third post-operative day. Discussion RIPC is a promising strategy to reduce IR injury in liver transplant recipients as there is a clear experimental basis, and the intervention is both inexpensive and easy to perform. This is the first trial to investigate RIPC in liver transplant recipients. Trial registration Clinicaltrials.gov NCT00796588 Electronic supplementary material The online version of this article (doi:10.1186/s13737-016-0033-4) contains supplementary material, which is available to authorized users.

Objective This study sought to compare the perioperative outcomes of interventions aiming to decrease ischemia–reperfusion (IR) injury during elective liver resection. Method A comprehensive literature search was performed to identify randomized controlled trials. A Bayesian network metaanalysis was performed using the Markov chain Monte Carlo method in WinBUGS following the guidelines of the National Institute for Health and Clinical Excellence Decision Support Unit. Odds ratios for binary outcomes and mean differences for continuous outcomes were calculated using a fixed effect model or a random effects model according to model fit. Results Forty-four trials with 2,457 patients having undergone liver resection were included and were divided into 8 classes of interventions aimed at decreasing IR injury and a control group, which was hepatectomy alone. There was no difference between the different interventions in mortality, quantity of blood transfusion, and durations of stay in an intensive therapy unit between any pairwise comparisons. Patients treated with ischemic preconditioning, cardiovascular modulators, and miscellaneous interventions had significantly fewer serious adverse events compared with patients undergoing liver resection alone. Ischemic preconditioning patients had significantly fewer transfusion proportions and shorter operative time than patients treated with steroids. Ischemic preconditioning had significantly less operative blood loss compared with all other interventions, and a lesser duration of hospital stay than hepatectomy alone. Sensitivity analysis showed that the drugs sevoflurane (a volatile anesthetic), verapamil (a calcium channel blocker), and gabexate mesilate (a thrombin inhibitor) produced fewer serious adverse events compared with hepatectomy alone. Conclusion Ischemic preconditioning resulted in multiple beneficial clinical endpoints and further RCTs seem to be needed to confirm its clinical benefits.