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The futility of liver transplantation in elderly recipients remains under debate in the HCV eradication era.The aim was to assess the effect of older age on outcome after liver transplantation. We used the ELTR to study the relationship between recipient age and post-transplant outcome. Young and elderly recipients were compared using a PSM method.A total of 10,172 cases were analysed. Recipient age65 years was identified as an independent risk factor associated with reduced patient survival (HR:1.42 95%CI:1.23-1.65,p 0.001). After PSM, 2124 patients were matched, and the same association was found between elderly recipients and patient survival and graft survival (p 0.001). As hepatocellular carcinoma and alcoholic cirrhosis were independent prognostic factors for patient and graft survival a propensity score-matching was performed for each. Patient and graft survival were significantly worse (p 0.05) in the alcoholic cirrhosis elderly group. However, patient and graft survival in the hepatocellular carcinoma cohort were similar (p 0.05) between groups.Liver transplantation is an acceptable and safe curative option for elderly transplant candidates, with worse long-term outcomes compare to young candidates. The underlying liver disease for liver transplantation has a significant impact on the selection of elderly patients.

Background Multiple risk scores claim to predict the probability of postoperative pancreatic fistula (POPF) after pancreatoduodenectomy. However, it is unclear which scores have undergone external validation, and which score is the most accurate. Objective To identify risk scores for POPF, and assess the clinical validity of these scores. Methods Areas under receiving operator characteristic curve (AUROCs) were extracted from studies that performed external validation of POPF risk scores. These were pooled for each risk score, using intercept-only random-effects meta-regression models. Results Systematic review identified 34 risk scores, of which six had been subjected to external validation, and so were included in the meta-analysis, namely the Tokyo (N=2 validation studies), Birmingham (N=5), FRS (N=19), a-FRS (N=12), m-FRS (N=3) and ua-FRS (N=3) scores. The overall predictive accuracies were found to be similar for all six scores, with pooled AUROCs of 0.61, 0.70, 0.71, 0.70, 0.70 and 0.72, respectively. Considerably heterogeneity was observed, with I2 statistics ranging from 52.1-88.6%. Conclusion Most risk scores lack external validation; where this was performed, risk scores were found to have limited predictive accuracy. . Consensus is needed for which score to use in clinical practice. Due to the limited predictive accuracy, future studies to derive a more accurate risk score are warranted.

Background Delayed biliary strictures (DBS) after cholecystectomy are uncommon and little is known of their aetiology or long-term consequences. The aims of this study were to investigate the clinical and economic impact of DBS after cholecystectomy. Methods Patients who developed DBS after cholecystectomy were identified from a prospectively collected and maintained database. Risk factors for stricture development, quality of life (QoL) and long-term biliary complication rates were explored. Costs of treatment and follow up were determined. The same outcomes among patients with minor or major bile duct injury (BDI) were used as a comparison. Results Among 44 patients, a laparoscopic converted to open procedure or post cholecystectomy bile leak affected some 18 and 12 patients respectively. Most DBS required surgical treatment (40). Over a median follow-up of 8.9 years after DBS treatment, 16 (36%) patients developed biliary complications (similar to minor, 26%, and major BDI, 40%) and 1 patient died of causes related to the biliary stricture. Costs of treating DBS and its follow up (£14,309.26 per patient), were similar to previously reported costs for major BDI (£15,784). Conclusion DBS typically occur after a technically and/or complicated cholecystectomy. Clinical, economic and QoL outcomes are similar to patients with major BDI.

Background The aim of the current study is to investigate the variations of anatomical (LVRem%) and functional remnant volumes (fLVRem%) and the dynamic uptake of Technetium-Mebrofinate (FRLF) measured from 99m Technetium-Mebrofinate SPECT-CT scan (TMSCT) in patients at high risk of post-hepatectomy liver failure (PHLF). Methods Variations in the measures of LVRem% and fLVRem% were assessed. The predictive accuracies of LVRem%, fLVRem% and FRLF with respect to PHLF were reported. Results From the N = 92 scans performed, LVRem% and fLVRem% returned identical results in 15% of cases, and ±10 percentage points in 79% of cases. Some patients had larger discrepancies, with difference of >10 percentage points in 21% of cases. The difference was significant in those with primary liver cancers (−4.4 ± 9.2, p = 0.002). For the N = 29 patients that underwent surgery as planned on TMSCT, FRLF was a strong predictor of PHLF, with an AUROC of 0.83 (p = 0.005). Conclusion TMSCT is emerging as a useful modality in pre-operative assessment of patients undergoing major liver resection. For those with primary liver cancer, there is a significant variation in the anatomical and functional distributions that needs considered in surgical planning. Reduced FRLF, measured as the dynamic uptake in the future liver remnant, is a strong predictor of PHLF.

Intra-operative blood salvage (IBS) reduces the use of allogeneic blood transfusion. However, safety of IBS during liver transplantation (LT) for hepatocellular carcinoma (HCC) is questioned due to fear for dissemination of circulating malignant cells. This study aims to assess safety of IBS. HCC patients who underwent LT from January 2006 through December 2019 were included. Patients in whom IBS was used were propensity score matched (1:1) to control patients. Disease-free survival and time to HCC recurrence were assessed with Cox regression models and competing risk models. IBS was used in 192/378 HCC LT recipients, and 127 patients were propensity score matched. Cumulative disease-free survival at 12 and 60 months was 85% and 63% for the IBS group versus 90% and 68% for the no-IBS group. Use of IBS was not associated with impaired disease-free survival (HR 1.07, 95%CI: 0.65–1.76, P = 0.800) nor with increased HCC recurrence (Cause-specific cox model: HR 0.79, 95%CI: 0.36–1.73, P = 0.549, Fine and Gray model: HR: 0.79, 95%CI 0.40–1.57, P = 0.50). In conclusion, IBS during LT did not increase the risk for HCC recurrence. IBS is a safe procedure in HCC LT recipients to reduce the need for allogenic blood transfusion.

Normothermic machine perfusion (NMP) allows objective assessment of donor liver transplantability. Several viability evaluation protocols have been established, consisting of parameters such as perfusate lactate clearance, pH, transaminase levels, and the production and composition of bile. The aims of this study were to assess 3 such protocols, namely, those introduced by the teams from Birmingham (BP), Cambridge (CP), and Groningen (GP), using a cohort of high-risk marginal livers that had initially been deemed unsuitable for transplantation and to introduce the concept of the viability assessment sensitivity and specificity. To demonstrate and quantify the diagnostic accuracy of these protocols, we used a composite outcome of organ use and 24-month graft survival as a surrogate endpoint. The effects of assessment modifications, including the removal of the most stringent components of the protocols, were also assessed. Of the 31 organs, 22 were transplanted after a period of NMP, of which 18 achieved the outcome of 24-month graft survival. The BP yielded 94% sensitivity and 50% specificity when predicting this outcome. The GP and CP both seemed overly conservative, with 1 and 0 organs, respectively, meeting these protocols. Modification of the GP and CP to exclude their most stringent components increased this to 11 and 8 organs, respectively, and resulted in moderate sensitivity (56% and 44%) but high specificity (92% and 100%, respectively) with respect to the composite outcome. This study shows that the normothermic assessment protocols can be useful in identifying potentially viable organs but that the balance of risk of underuse and overuse varies by protocol.

Background. The influence of sex on primary sclerosing cholangitis (PSC), pre- and postliver transplantation (LT) is unclear. Aims are to assess whether there have been changes in incidence, profile, and outcome in LT-PSC patients in Europe with specific emphasis on sex. Methods. Analysis of the European Liver Transplant Registry database (PSC patients registered before 2018), including baseline demographics, donor, biochemical, and clinical data at LT, immunosuppression, and outcome. Results. European Liver Transplant Registry analysis (n = 6463, 32% female individuals) demonstrated an increasing number by cohort (1980-1989, n = 159; 1990-1999, n = 1282; 2000-2009, n = 2316; 2010-2017, n = 2549) representing on average 4% of all transplant indications. This increase was more pronounced in women (from 1.8% in the first cohort to 4.3% in the last cohort). Graft survival rate at 1, 5, 10, 15, 20, and 30 y was 83.6%, 70.8%, 57.7%, 44.9%, 30.8%, and 11.6%, respectively. Variables independently associated with worse survival were male sex, donor and recipient age, cholangiocarcinoma at LT, nondonation after brain death donor, and reduced size of the graft. These findings were confirmed using a more recent LT population closer to the current standard of care (LT after the y 2000). Conclusions. An increasing number of PSC patients, particularly women, are being transplanted in European countries with better graft outcomes in female recipients. Other variables impacting outcome include donor and recipient age, cholangiocarcinoma, nondonation after brain death donor, and reduced graft size.

Vaccine-induced immune thrombosis and thrombocytopenia (VITT) syndrome is a new entity, characterised by severe thrombocytopenia and multiple sites of thrombosis1 . The presumed mechanism is driven by anti-platelet factor 4 (PF4) antibodies causing platelet activation1 . Donors with VITT syndrome have a particular relevance for liver transplantation (LT), due to the associated risk of passenger lymphocyte syndrome, and a predisposition for porto-mesenteric or hepatic vein thrombosis2 .

Summary High‐risk combinations of recipient and graft characteristics are poorly defined for liver retransplantation (reLT) in the current era. We aimed to develop a risk model for survival after reLT using data from the European Liver Transplantation Registry, followed by internal and external validation. From 2006 to 2016, 85 067 liver transplants were recorded, including 5581 reLTs (6.6%). The final model included seven predictors of graft survival: recipient age, model for end‐stage liver disease score, indication for reLT, recipient hospitalization, time between primary liver transplantation and reLT, donor age, and cold ischemia time. By assigning points to each variable in proportion to their hazard ratio, a simplified risk score was created ranging 0–10. Low‐risk (0–3), medium‐risk (4–5), and high‐risk (6–10) groups were identified with significantly different 5‐year survival rates ranging 56.9% (95% CI 52.8–60.7%), 46.3% (95% CI 41.1–51.4%), and 32.1% (95% CI 23.5–41.0%), respectively (P, The retransplantation risk score.

Key points The first #FGDebates of 2021 tackled ‘Controversies in liver transplantation’ in a double-header inspired by the recent liver transplantation guidelines.1 2 The debates stimulated much discussion with nearly 900 tweets from over 100 participants across the two debates. This fantastic interaction generated a cumulative 3.7 million impressions worldwide with both debates ranking in the top 5 #FGDebates of all time for total impressions made. In this article, we aim to discuss the key discussion points from each of the #FGDebates. Liver transplantation for patients with alcohol use disorders (AUDs) has historically been viewed as a controversial area for both the general public and healthcare profession. This was largely due to the perceived ‘self-inflicted’ component and the risk of recidivism post-transplant.3 However, the majority of our attendees felt that it was the correct time to assess our patient with an AUD (figure 1) and alcohol-related liver disease remains the most common aetiology at registration for liver transplantation in the UK with good long-term outcomes.4 A common misconception is that patients require a period of 6 months abstinence prior to referral for assessment. While a period of 3 months abstinence may demonstrate the potential for recompensation, there is no absolute rule for abstinence duration prior to assessment in the UK other than patients must be abstinent.1 However, these patients should be assessed for their individual risk of return to drinking and should …

Vaccine-induced thrombosis and thrombocytopenia (VITT) may follow immunisation with the ChAdOx1 nCoV-19 vaccine against SARS-CoV-2. Autoantibodies to platelet factor 4 (PF4) may mediate VITT through antibody-dependent platelet activation, though the underlying etiology is uncertain. Anti-PF4 antibodies are also seen in heparin-induced thrombocytopenia, though most cases of VITT do not have prior heparin exposure. More than 20 million people in the United Kingdom (UK) have received the ChAdOx1 nCoV-19 vaccine.

The aim of this study was to investigate the influence of resection margin status in patients with KRAS mutations (mt-KRAS) when compared to those with wild-type KRAS (wt-KRAS) on long-term outcomes in patients with resected CRLM.All patients who underwent resection of CRLM with curative intent between January 2011 and December 2016 and had a KRAS type recorded were included in the study. Overall survival (OS), as well as death-censored overall (RFS) and liver-specific (LS-RFS) recurrence-free survival between KRAS types and the margin status within KRAS subgroups were compared using Cox regression models.Data were available for N = 500 patients (30.4% mt-KRAS). mt-KRAS status was independently associated with significantly shorter OS. Within the wt-KRAS subgroup, smaller margins were found to be associated with significantly shorter death-censored LS-RFS (p 0.001), with HRs of 1.93 (p = 0.005) for 1-4 mm margins and 2.83 (p 0.001) for1 mm margins, relative to those with clear margins. No such association was observed in the mt-KRAS subgroup (p = 0.721).The resection margin status is of greater importance in patients with wt-KRAS. Such information could be useful in the operative planning, especially for those with multiple metastatic deposits, and also in the post-operative counselling and surveillance based on the margin and KRAS status.

The aim of this study was to evaluate potential risk factors associated with benign lesions and perihilar cholangiocarcinoma (PHC) in patients presenting with proximal biliary strictures (PBS).Patients with PBS who were referred to a specialist HPB centre between 2008 and 2016 were identified. Patients with primary sclerosing cholangitis, metastatic PHC or hilar obstruction by a peripheral tumour were excluded. The final diagnosis was determined either by (1) resection histology or (2) combination of biopsy and clinical course. Multivariable analysis of clinical, laboratory and radiological data was undertaken to identify independent predictors of benign and malignant lesions.155 consecutive patients were identified, including 25 patients (16%) with benign PBS. Abdominal pain (odds ratio [OR] 3.36; p = 0.027), serum CA19.9 100 U/ml (OR 10.35; p = 0.001), and absence of mass on imaging (OR 4.66; p = 0.004) were all associated with the presence of benign lesions on multivariable analysis.This study has identified several independent variables that may differentiate between benign and malignant proximal biliary strictures. A larger multi-institutional study would be warranted to validate these findings, and to develop a risk score to stratify patients with suspected PHC.

Background Positive margins in pancreatoduodenectomy (PD) for pancreatic cancer, specifically the superior mesenteric artery (SMA) margin, are associated with worse outcomes. Local therapies targeting these margins could impact on recurrence. This study analysed recurrence-patterns to identify whether strategies to control local disease could have a meaningful impact. Methods (I) Systematic review to define recurrence patterns and resection margin status. (II) Additional retrospective study of PD performed at our centre. Results In the systematic review, 23/617 evaluated studies were included (n = 3815). Local recurrence was observed in 7–69%. SMA margin (6 studies) was positive in 15–35%. In the retrospective study (n = 204), local recurrence was more frequently observed with a positive SMA margin (66 vs.45%; p = 0.005). Furthermore, in a multivariate cox-proportional hazard model, only a positive SMA margin was associated with disease recurrence (HR 1.615; 95%CI 1.127–2.315; p = 0.009). Interestingly, median overall survival was 20 months and similar for patients who developed local only, metastases only or simultaneous recurrence (p = 0.124). Conclusion Local recurrence of pancreatic cancer is common and associated with similar mortality rates as those who present with simultaneous or metastatic recurrence. Involvement of the SMA margin is an independent predictor for disease progression and should be the target of future adjuvant local therapies.

Outcomes after Strasberg grade E bile duct injury have been widely reported. However, there are comparatively few reports of outcomes after Strasberg A to D bile duct injury. Therefore, the aim of this study was to comprehensively evaluate the long-term clinical and economic impact of Strasberg A to D bile duct injury.Patients with Strasberg A to D bile duct injury were identified from a prospectively collected and maintained database. Long-term biliary complication rates, as well as treatment costs were then estimated, and compared across Strasberg injury grades.A total of N = 120 patients were identified, of whom N = 49, 13, 20, and 38 had Strasberg grade A, B, C, and D bile duct injury, respectively. Surgical repair was most commonly performed in Strasberg grade D injuries (74% vs 8%-20% in lower grades, P.001). By 5 years post bile duct injury, the estimated long-term biliary complication rate was 40% in Strasberg grade D injuries, compared with 15% in Strasberg grade A (P = .022). A significant difference in total treatment and follow-up costs was also detected (P.001), being highest in Strasberg grade D injuries (mean £11,048/US$14,252 per patient) followed by the Strasberg grade B group (mean £10,612/US$13,689 per patient).Strasberg grade A to D injuries lead to considerable long-term morbidity and cost. Strasberg grade D injuries are typically managed surgically and result in the highest complication rate and treatment costs. Strasberg grade B injuries lead to a similar complication rate and treatment cost but are often managed without surgery.

Introduction Management of posttraumatic bile leak has evolved over time in our unit, from endoscopic retrograde cholangiopancreatography (ERCP) stenting to intraperitoneal drainage (IPD) alone as first-line treatment for intraperitoneal bile leak. Materials and Methods Retrospective review of liver trauma patients from 2002 to 2017. Demographics, time and mode of diagnosis of bile leak, management, and outcome were analyzed of the box plot. Results In 118 patients, there were 28 traumatic bile leaks. Eighteen were free intraperitoneal and 10 were localized bilomas. The median time of diagnosis was 6 days following injury. The modes of diagnosis were preemptive hepatobiliary scintigraphy (18), computed tomography (CT) or ultrasound (7), and laparotomy (3). Free intraperitoneal biliary leak management included 11 IPD alone, 3 IPD plus ERCP, 2 IPD plus transcystic biliary stent (TBS), 1 operative cholangiogram, and 1 no intervention. Median time of IPD duration was 7 days (4–95) in IPD alone versus 14 days (6–40) in IPD + ERCP/TBS (p = 0.3). Median inpatient length of stay was 13 days (8–44) in IPD alone versus 12 days (8–22) in IPD + ERCP/TBS (p = 0.4). Conclusion Placement of IPD alone, as first-line treatment, is safe and effective in the management of intraperitoneal bile leaks, avoiding the costs and potential complications of ERCP.

Background Several studies have reported the effect of bile duct injury (BDI) on health-related quality of life (HRQOL) with conflicting results. This systematic review aims to study the impact of patient and treatment factors on HRQOL after BDI. Methods A search of the PubMed database was performed and studies were reviewed as per the PRISMA guidelines. Selected studies (n = 11) were then divided into two subgroups depending on whether they found HRQOL to be similar or worse between BDI and control groups. Pooled rates of surgical repair and major BDI were calculated for each of these subgroups. Results Surgical repair rates were 99% (95% CI: 96%–99%) in studies where the BDI patients had similar outcomes to controls, compared to 78% (40%–100%) where their outcomes were significantly worse (p = 0.091). The major BDI rate was 51% (95% CI: 42%–61%) in studies where the BDI patients had similar outcomes to controls, compared to 72% (41%–94%) where their outcomes were significantly worse (p = 0.322). Considerable heterogeneity was present within the two subgroups (I2: 68–99%). Discussion HRQOL may be adversely affected amongst patients with BDI who do not undergo surgical repair. Significant heterogeneity of data suggests the need for standardised HRQOL tools and injury severity systems when assessing outcomes after BDI.

Post-operative pancreatic fistula (POPF) is a major cause of morbidity following pancreatoduodenectomy. The risk of POPF varies between individuals and thus assessment without risk adjustment is crude. However, despite the availability of numerous scores to determine risk, no study has provided a risk adjusted assessment of POPF outcomes.The observed and risk adjusted occurrence of POPF from consecutive patients operated upon by eight surgeons were recorded. Surgeons varied in experience from newly appointed (n = 5) to established (n = 3). CUSUM (cumulative sum) analysis was used to assess performance.104 POPF occurred among 519 patients (20.0%). The occurrence of POPF was significantly lower among experienced surgeons (20/186, 10.7% vs 84/333, 25.2%; p 0.001). Following risk adjustment surgeons observed 16.6 fewer to 6.5 excess POPF per 100 patients than predicted. Analysis of the CUSUM plots demonstrated the experienced surgeons performed steadily with a gradual reduction in observed POPF compared to what was predicted. The new surgeon's performance was less consistent and evidence of a learning curve was observed with steady improvement occurring after 50-70 patients.Risk adjusted assessment of POPF demonstrates differences between experienced and less experienced surgeons. This method could be used to audit practice and observe effects of changes to technique.

Background The aim of this study was to develop and validate a risk score to predict overall survival (OS) in patients undergoing surgical resection for hepatocellular carcinoma in non-cirrhotic liver (NC-HCC). Methods Patients who underwent resection for NC-HCC between 2004 and 2013 were identified from the SEER database. A derivation set of 75% of this cohort was used to develop a risk score. This was then internally validated on the remaining patients, and externally validated using a cohort of patients from The HPB Unit, Birmingham, UK. Results A total of 3897 patients were included from the SEER database, with a median post-diagnosis survival of 59 months. In the derivation set, multivariable analyses identified male sex, increasing tumour size, the presence of multiple tumours, bilobar tumours and major vascular invasion as adverse prognostic factors. A risk score generated from these factors was significantly predictive of OS, and was used to classify patients into low, medium and high-risk groups. These groups had a five-year OS of 69%, 51% and 19% in the internal, and 73%, 50% and 45% in the external validation sets. Conclusion The proposed risk score is useful in the selection, pre-operative consenting and counselling of patients for surgery and to allow patients to make an informed decision regarding treatment.

Normothermic machine perfusion (NMP) provides clinicians an opportunity to assess marginal livers before transplantation. However, objective criteria and point‐of‐care (POC) biomarkers to predict risk and guide decision making are lacking. In this investigation, we characterized trends in POC biomarkers during NMP and compared primate donation after circulatory death (DCD) livers with short and prolonged warm ischemic injury. Following asystole, livers were subjected to either 5 minutes (DCD‐5min, n = 4) or 45 minutes (DCD‐45min, n = 4) of warm ischemia time. Livers were flushed with heparinized UW solution, and preserved in cold storage before NMP. During flow‐controlled NMP, circulating perfusate and tissue biopsies were collected at 0, 2, 4, 6, and 8 hours for analysis. DCD‐45min livers had greater terminal portal vein pressure (8.5 vs. 13.3 mm Hg, P = 0.027) and terminal portal vein resistance (16.3 vs. 32.4 Wood units, P = 0.005). During perfusion, DCD‐45min livers had equivalent terminal lactate clearance (93% vs. 96%, P = 0.344), greater terminal alanine aminotransferase (163 vs. 883 U/L, P = 0.002), and greater terminal perfusate gamma glutamyltransferase (GGT) (5.0 vs. 31.7 U/L, P = 0.002). DCD‐45min livers had higher circulating levels of flavin mononucleotide (FMN) at hours 2 and 4 of perfusion (136 vs. 250 ng/mL, P = 0.029; and 158 vs. 293 ng/mL, P = 0.003; respectively). DCD‐5min livers produced more bile and demonstrated progressive decline in bile lactate dehydrogenase, whereas DCD‐45min livers did not. On blinded histologic evaluation, DCD‐45min livers demonstrated greater injury and necrosis at late stages of perfusion, indicative of nonviability. Conclusion: Objective criteria are needed to define graft viability during NMP. Perfusate lactate clearance does not discriminate between viable and nonviable livers during NMP. Perfusate GGT and FMN may represent POC biomarkers predictive of liver injury during NMP., We characterized trends in point‐of‐care biomarkers during normothermic machine liver perfusion using non‐human primate DCD livers with short versus prolonged warm ischemic injury. Perfusate gamma‐glutamyl transferase and flavin mononucleotide may represent novel point‐of‐care biomarkers predictive of liver injury during NMP.

Full-left-full-right split liver transplantation (FSLT) for adult recipients, may increase the availability of liver grafts, reduce waitlist time, and benefit recipients with below-average body weight. However, FSLT may lead to impaired graft and patient survival. This study aims to assess outcomes after FSLT. Five databases were searched to identify studies concerning FSLT. Incidences of complications, graft- and patient survival were assessed. Discrete data were pooled with random-effect models. Graft and patient survival after FSLT were compared with whole liver transplantation (WLT) according to the inverse variance method. Vascular complications were reported in 25/273 patients after FSLT (Pooled proportion: 6.9%, 95%CI: 3.1–10.7%, I2: 36%). Biliary complications were reported in 84/308 patients after FSLT (Pooled proportion: 25.6%, 95%CI: 19–32%, I2: 44%). Pooled proportions of graft and patient survival after 3 years follow-up were 72.8% (95%CI: 67.2–78.5, n = 231) and 77.3% (95%CI: 66.7–85.8, n = 331), respectively. Compared with WLT, FSLT was associated with increased graft loss (pooled HR: 2.12, 95%CI: 1.24–3.61, P = 0.006, n = 189) and patient mortality (pooled HR: 1.81, 95%CI: 1.17–2.81, P = 0.008, n = 289). FSLT was associated with high incidences of vascular and biliary complications. Nevertheless, long-term patient and graft survival appear acceptable and justify transplant benefit in selected patients.

The incorporation of machine preservation technology into clinical solid-organ transplantation is becoming a routine procedure in many institutions around the globe. As experience with these modalities accrues over time, it is important to refine their application. In combination with laboratory based NMP experiments, early patient series allowed us to establish NMP viability criteria that were applied in the VITTAL trial.

Survival rates for patients following liver transplantation exceed 90% at 12 months and approach 70% at 10 years. Part 1 of this guideline has dealt with all aspects of liver transplantation up to the point of placement on the waiting list. Part 2 explains the organ allocation process, organ donation and organ type and how this influences the choice of recipient. After organ allocation, the transplant surgery and the critical early post-operative period are, of necessity, confined to the liver transplant unit. However, patients will eventually return to their referring secondary care centre with a requirement for ongoing supervision. Part 2 of this guideline concerns three key areas of post liver transplantation care for the non-transplant specialist: (1) overseeing immunosuppression, including interactions and adherence; (2) the transplanted organ and how to initiate investigation of organ dysfunction; and (3) careful oversight of other organ systems, including optimising renal function, cardiovascular health and the psychosocial impact. The crucial significance of this holistic approach becomes more obvious as time passes from the transplant, when patients should expect the responsibility for managing the increasing number of non-liver consequences to lie with primary and secondary care.

Backgrounds/Aims Approximately 60-80% of patients with intrahepatic cholangiocarcinoma (iCCA) are not suitable for surgical resection due to advanced disease at presentation. This review assesses the role of surgical resection followed by down staging treatment in the management of patients with locally advanced iCCA. Methods A systematic review and pooled analysis were performed of the relevant published studies published between January 2000-December 2018. The primary outcome measure was overall survival. Secondary outcome measures were rates of clinical benefit, margin-negative (R0) resections, overall and surgery-specific complications, and post-operative mortality. Results Eighteen cohort studies with 1880 patients were included in the review. The median overall survival in all patients was 14 months (range, 7-18 months). Patients undergoing resection following down staging had significantly longer survival than those who did not (median: 29 vs. 12 months, p

Liver transplantation is a highly successful treatment for all types of liver failure, some non-liver failure indications and liver cancer. Most referrals come from secondary care. This first part of a two-part guideline outlines who to refer, and how that referral should be made, including patient details and additional issues such as those relevant to alcohol and drug misuse. The process of liver transplant assessment involves the confirmation of the diagnosis and non-reversibility, an evaluation of comorbidities and exclusion of contraindications. Finally, those making it onto the waiting list require monitoring and optimising. Underpinning this process is a need for good communication between patient, their carers, secondary care and the liver transplant service, synchronised by the transplant coordinator. Managing expectation and balancing the uncertainty of organ availability against the inevitable progression of underlying liver disease requires sensitivity and honesty from all healthcare providers and the assessment of palliative care needs is an integral part of this process.

Background Acute kidney injury (AKI) is a frequent complication after liver transplantation. Although numerous risk factors for AKI have been identified, their cumulative impact remains unclear. Our aim was therefore to design a new model to predict post-transplant AKI. Methods Risk analysis was performed in patients undergoing liver transplantation in two centres (n = 1230). A model to predict severe AKI was calculated, based on weight of donor and recipient risk factors in a multivariable regression analysis according to the Framingham risk-scheme. Results Overall, 34% developed severe AKI, including 18% requiring postoperative renal replacement therapy (RRT). Five factors were identified as strongest predictors: donor and recipient BMI, DCD grafts, FFP requirements, and recipient warm ischemia time, leading to a range of 0–25 score points with an AUC of 0.70. Three risk classes were identified: low, intermediate and high-risk. Severe AKI was less frequently observed if recipients with an intermediate or high-risk were treated with a renal-sparing immunosuppression regimen (29 vs. 45%; p = 0.007). Conclusion The AKI Prediction Score is a new instrument to identify recipients at risk for severe post-transplant AKI. This score is readily available at end of the transplant procedure, as a tool to timely decide on the use of kidney-sparing immunosuppression and early RRT.

Complications and litigation after bile duct injury (BDI) result in clinical and economic burden. The aim of this study was to comprehensively evaluate the long-term clinical and economic impact of major BDI.Patients with long-term follow-up after Strasberg E BDI were identified. Costs of treatment and litigation were the primary outcome. Relationships between these outcomes and repair factors, like timing of repair and surgeon expertise, were secondary outcomes.Among 139 patients with a median follow up of 10.7 years, 40% of patients developed biliary complications. Repairs by non-specialist surgeons had significantly higher follow up and treatment costs than those by specialists (£25,814 vs. £14,269, p 0.001). Estimated litigation costs were higher in delayed than immediate repairs (£23,295 vs. £12,864). As such, the lowest average costs per BDI are after immediate specialist repair and the highest after delayed non-specialist repair (£27,133 vs. £49,109, ×1.81 more costly, p 0.001). Repair by a non-specialist surgeon (HR: 4.00, p 0.001) and vascular injury (HR: 2.35, p = 0.013) were significant independent predictors of increased complication rates.Costs of major BDI are considerable. They can be reduced by immediate on-table repair by specialist surgeons. This must therefore be considered the standard of care wherever possible.

Liver transplantation is an effective intervention for end-stage liver disease, fulminant hepatic failure, and early hepatocellular carcinoma. Yet, there is marked patient-to-patient variation in liver transplantation outcomes. This calls for novel diagnostics to enable rational deployment of donor livers. Metabolomics is a postgenomic high-throughput systems biology approach to diagnostic innovation in clinical medicine. We report here an original systematic review of the metabolomic studies that have identified putative biomarkers in the context of liver transplantation. Eighteen studies met the inclusion criteria that involved sampling of blood (

Pre-operative risk factors for post-operative ventilation and their influence on survival after pancreaticoduodenectomy for malignancy are unknown.Totally 391 patients operated in Hannover, Germany were investigated with multivariable logistic regression and Cox regression modeling to identify independent risk factors for post-operative ventilation ≥6 h, patient survival and 90-day mortality. And 84 patients operated in Birmingham, United Kingdom were analyzed to assess the external relevance of findings.Longer operations, history of thrombosis, intra-operative blood transfusion, lower estimated glomerular filtration rates (eGFR) and higher values of the age at operation divided by the Horovitz Quotient independently increased the risk of post-operative ventilation ≥ 6 h in German patients (n = 108; 27.6%) (P0.050). Blood transfusion and lower pre-operative eGFR levels increased the risk of early death in German patients significantly and independently of established prognostic factors. A history of thrombosis and lower eGFR levels were also independent significant risk factors for 90-day mortality in German patients but not in English patients. None of the English patients received post-operative ventilation. Significantly more German patients were75 years, had a history of thrombosis, received blood transfusions, and had significantly worse lung function parameters. pT4 tumors were detected in 18 German patients (4.6%), but not in the English patients.Identified risk factors for post-operative ventilation are clinically relevant in Germany but not in England and may be used to lower mortality risk. The German and the English cohorts displayed significant differences in the approach to patient selection and early post-operative extubation.

Normothermic machine perfusion (NMP) of liver grafts is increasingly being incorporated in clinical practice. Current evidence has shown NMP plays a role in reconditioning the synthetic and energy capabilities of grafts. Intraoperative coagulation profile is a surrogate of graft quality and preservation status; however, to date this aspect has not been documented.The liver transplantation recipients who received NMP liver grafts in the QEHB between 2013 and 2016 were compared in terms of intraoperative thromboelastography characteristics (R time, K time, α-angle, maximum amplitude, G value, and LY30) to a propensity score-matched control group, where the grafts were preserved by traditional static cold storage (SCS).After propensity matching, none of the thromboelastography characteristics were found to differ significantly between the 72 pairs of SCS and NMP organs when measured preimplantation. However, postimplantation, NMP organs had significantly shorter K time (median: 2.8 vs 3.6 min, P = 0.010) and R + K time (11.4 vs 13.7 min, P = 0.016), as well as significantly larger α-angle (55.9° vs 44.8°, P = 0.002), maximum amplitude (53.5 vs 49.6 mm, P = 0.044), and G values (5.8 vs 4.9k dynes/cm, P = 0.043) than SCS organs. Hyperfibrinolysis after implantation was also mitigated by NMP, with fewer patients requiring aggressive factor correction during surgery (LY30 = 0, NMP vs SCS: 83% vs 60%, P = 0.004). Consequently, NMP organs required significantly fewer platelet units to be transfused during the transplant procedure (median: 0 vs 5, P = 0.001).In this study, we have shown that NMP liver grafts return better coagulation profiles intraoperatively, which could be attributed to the preservation of liver grafts under physiological conditions.

Post hepatectomy liver failure (PHLF) is a serious complication in patients undergoing liver resection. This study hypothesized that a new pre-operative risk score developed through statistical modeling to predict PHLF could be used to stratify patients at higher risk of PHLF.Patients who underwent hepatectomy between 2008 and 2016 were included in the derivation and validation cohorts. A multivariable binary logistic regression model was performed to identify predictors of PHLF, and a prognostic score was derived.A total of 1269 patients were included in the derivation cohort. PHLF was encountered in 13.1% and was associated with significantly increased 90-day mortality and prolonged post-operative hospital stay (both p 0.001). Multivariable analysis identified the extent of surgery (p 0.001) and pre-operative bilirubin (p = 0.015), INR (p 0.001), and creatinine (p = 0.048) to be independent predictors of PHLF. A risk score derived from these factors returned an area under the ROC curve (AUROC) of 0.816 (p 0.001) for an internal validation cohort (N = 453), significantly outperforming the MELD score (AUROC: 0.643).The PHLF risk score could be used to stratify the risk of PHLF among patients planned for hepatectomy.

Patient selection for combined liver-kidney transplantation (CLKT) is a current issue on the background of organ shortage. This study aimed to compare outcomes and post-transplant renal function for patients receiving CLKT and liver transplantation alone (LTA) based on native renal function using estimated glomerular filtration rate (eGFR) stratification. Using the UK National transplant database (NHSBT) 6035 patients receiving a LTA (N = 5912; 98%) or CLKT (N = 123; 2%) [2001-2013] were analysed, and stratified by KDIGO stages of eGFR at transplant (eGFR group-strata). There was no difference in patient/graft survival between LTA and CLKT in eGFR group-strata (P > 0.05). Of 377 patients undergoing renal replacement therapy (RRT) at time of transplantation, 305 (81%) and 72 (19%) patients received LTA and CLKT respectively. A significantly greater proportion of CLKT patients had severe end-stage renal disease (eGFR < 30 ml/min/1.73 m2 ) at 1 year post-transplant compared to LTA (9.5% vs. 5.7%, P = 0.001). Patient and graft survival benefit for patients on RRT at transplantation was favouring CLKT versus LTA (P = 0.038 and P = 0.018, respectively) but the renal function of the long-term survivors was not superior following CLKT. The data does not support CLKT approach based on eGFR alone, and the advantage of CLKT appear to benefit only those who are on established RRT at the time of transplant.

Background Perioperative use of statins is reported to improve postoperative outcomes after cardiac and non-cardiovascular surgery. The aim of this study was to investigate the influence of statins on postoperative outcomes including complications of grade IIIa and above, posthepatectomy liver failure (PHLF), and 90-day mortality rates after liver resection. Methods Patients who underwent hepatectomy between 2013 and 2017 were reviewed to identify statin users and non-users (controls). Propensity matching was conducted for age, BMI, type of surgery and preoperative co-morbidities to compare subgroups. Univariable and multivariable analyses were performed for the following outcomes: 90-day mortality, significant postoperative complications and PHLF. Results Of 890 patients who had liver resection during the study period, 162 (18·2 per cent) were taking perioperative statins. Propensity analysis selected two matched groups, each comprising 154 patients. Overall, 81 patients (9·1 per cent) developed complications of grade IIIa or above, and the 90-day mortality rate was 3·4 per cent (30 patients), with no statistically significant difference when the groups were compared before and after matching. The rate of PHLF was significantly lower in patients on perioperative statins than in those not taking statins (10·5 versus 17·3 per cent respectively; P = 0·033); similar results were found after propensity matching (10·4 versus 20·8 per cent respectively; P = 0·026). Conclusion The rate of PHLF was significantly lower in patients taking perioperative statins, but there was no statistically significant difference in severe complications and mortality rates.

Knowledge of living donor liver transplantation (LDLT) for autoimmune liver diseases (AILDs) is scarce. This study analyzed survival in LDLT recipients registered in the European Liver Transplant Registry with autoimmune hepatitis, primary biliary cholangitis, primary sclerosing cholangitis (PSC) and the non-autoimmune disorder alcohol-related cirrhosis. In total, 29 902 individuals enrolled between 1998 and 2017 were analyzed, including 1003 with LDLT. Survival from >90 days after LDLT for AILDs in adults was 85.5%, 74.2%, and 58.0% after 5, 10, and 15 years. Adjusted for recipient age, sex, and liver transplantation era, adult PSC patients receiving LDLT showed increased mortality compared to donation after brain death (DBD) (hazard ratio [HR] = 1.95, 95% confidence interval [CI] = 1.36-2.80, p < .001). Pediatric PSC patients showed also increased mortality >90 days after LDLT compared to DBD (HR = 3.00, 95% CI 1.04-8.70, p = .043). Multivariate analysis identified several risk factors for death in adult PSC patients receiving LDLT including a male donor (HR = 2.49, p = .025). Adult PSC patients with LDLT versus DBD conferred increased mortality from disease recurrence (subdistribution hazard ratio [subHR] = 5.36, p = .001) and biliary complications (subHR = 4.40, p = .006) in multivariate analysis. While long-term outcome following LDLT for AILD is generally favorable, PSC patients with LDLT compared to DBD might be at increased risk of death., Astellas Pharma; Novartis; Institut Georges Lopez; Sandoz, The Organ Sharing Organizations: the French ABM (Sami Djabbour), the Dutch NTS (Maaike de Wolf), the Eurotransplant Foundation (Marieke Van Meel), the Spanish RETH (Gloria de la Rosa), the UK-Ireland NHSBT (Michael Daynes), and the Scanditransplant (Ilse Duus Weinreich) are acknowledged for the data cross-check and sharing with the ELTR. The European Liver Transplant Registry is supported by a grant from Astellas Pharma, Novartis, Institut Georges Lopez, and Sandoz and receives logistical support from the Paul Brousse Hospital (AP-HP).

The increasing disparity between the number of patients listed for transplantation and the number of suitable organs has led to the increasing use of extended criteria donors (ECDs). ECDs are at increased risk of developing ischaemia reperfusion injury and greater risk of post-transplant complications. Ischaemia reperfusion injury is a major complication of organ transplantation defined as the inflammatory changes seen following the disruption and restoration of blood flow to an organ—it is a multifactorial process with the potential to cause both local and systemic organ failure. The utilisation of machine perfusion under normothermic (37 degrees Celsius) and hypothermic (4–10 degrees Celsius) has proven to be a significant advancement in organ preservation and restoration. One of the key benefits is its ability to optimise suboptimal organs for successful transplantation. This review is focused on examining ischaemia reperfusion injury and how machine perfusion ameliorates the graft’s response to this.

Colorectal cancer is a prevalent disease worldwide, with more than 50% of patients developing metastases to the liver. Despite advances in improving resectability, most patients present with non-resectable colorectal liver metastases requiring palliative systemic therapy and locoregional disease control strategies. There is a growing interest in the use of liver transplantation to treat non-resectable colorectal liver metastases in well selected patients, leading to a surge in the number of studies and prospective trials worldwide, thereby fuelling the emerging field of transplant oncology. The interdisciplinary nature of this field requires domain-specific evidence and expertise to be drawn from multiple clinical specialities and the basic sciences. Importantly, the wider societal implication of liver transplantation for non-resectable colorectal liver metastases, such as the effect on the allocation of resources and national transplant waitlists, should be considered. To address the urgent need for a consensus approach, the International Hepato-Pancreato-Biliary Association commissioned the Liver Transplantation for Colorectal liver Metastases 2021 working group, consisting of international leaders in the areas of hepatobiliary surgery, colorectal oncology, liver transplantation, hepatology, and bioethics. The aim of this study was to standardise nomenclature and define management principles in five key domains: patient selection, evaluation of biological behaviour, graft selection, recipient considerations, and outcomes. An extensive literature review was done within the five domains identified. Between November, 2020, and January, 2021, a three-step modified Delphi consensus process was undertaken by the workgroup, who were further subgrouped into the Scientific Committee, Expert Panel, and Transplant Centre Representatives. A final consensus of 44 statements, standardised nomenclature, and a practical management algorithm is presented. Specific criteria for clinico-patho-radiological assessments with molecular profiling is crucial in this setting. After this, the careful evaluation of biological behaviour with bridging therapy to transplantation with an appropriate assessment of the response is required. The sequencing of treatment in synchronous metastatic disease requires special consideration and is highlighted here. Some ethical dilemmas within organ allocation for malignant indications are discussed and the role for extended criteria grafts, living donor transplantation, and machine perfusion technologies for non-resectable colorectal liver metastases are reviewed. Appropriate immunosuppressive regimens and strategies for the follow-up and treatment of recurrent disease are proposed. This consensus guideline provides a framework by which liver transplantation for non-resectable colorectal liver metastases might be safely instituted and is a meaningful step towards future evidenced-based practice for better patient selection and organ allocation to improve the survival for patients with this disease.

Hepatocyte necrosis is an undesired finding on liver allograft biopsy and donor transaminases are considered surrogate markers for donor liver allograft quality. Mild to moderate elevation of donor transaminases are not a contraindication to transplantation, however severe elevation often denotes ischaemic hepatocyte necrosis and these grafts are seldom considered for transplantation.

Introduction The UK has been severely affected by the COVID-19 pandemic. The impact on the adult population has been disproportionately higher when compared to children with consequent challenges to organ donation and liver transplantation (LT). Across the three UK paediatric liver centres there has only been a very small number of patients who tested positive for COVID-19 and all made a speedy and full recovery. We report here the response during the pandemic across the 3 paediatric LT centres. Methods A series of nationally agreed policy changes affecting the liver procurement, listing and transplant process were agreed during regular meetings with LT centre directors and NHSE. Actions at a local and national level were agreed to protect and maintain the paediatric LT programmes. Data were collected from 27/03/20 until 26/11/20 and compared with same time period for the years 2016–19. Results During the study period, there was a significant reduction in the adult population in the mean number of weekly liver offers, donors and LTs compared to before the pandemic with signs of recovery between the 1st and 2nd UK lockdown periods (figure 1). More specifically the number of livers offered nationally was reduced from an average 30–40/week to only Overall, 65–80 paediatric LTs are performed annually across the UK’s 3 paediatric centres. From March-November 2020 there were 58(82%) elective and 13(18%) super urgent (acute liver failure & hepatoblastoma) paediatric LTs performed. Donor Brain Dead (DBD) and Donor Cardiac Dead (DCDC) LTs were 54(76%) and 3(4%), respectively. Living related LT (LRLT) programme was sustained comprising 20% of LTs performed. The number of paediatric LTs performed during the pandemic was comparable to those performed yearly since 2016. The number of LT per paediatric centre for King’s College Hospital (KCH), Birmingham Children’s Hospital (BCH) and Leeds Liver Unit were 40 (56%), 15(21%) and 16(23%), respectively with excellent outcome. A 15-year-old girl from KCH diagnosed with Wilson disease presented with liver failure and became COVID-19 positive whilst listed. She underwent LT soon after becoming COVID-19 negative. No perioperative mortality was reported with excellent outcome so far in all. Conclusion The current COVID-19 pandemic had a significant impact on the UK adult LT programme. The paediatric programme LT was preserved despite a decrease in organ offering and retrieval nationally plus limitations on adult intensive care resources at a regional level. Overall, paediatric LT outcome remained very good.

Background Increasing numbers of successful paediatric liver transplantation (PLT) with improved survival rates reaching 90%at 10 years resulted in more children being listed for PLT but this was not associated with matching expansion in graft pool resulting in graft shortage. Reports including our published early experience showed promising short and intermediate term outcomes from DCD grafts in children. Aim To compare long-term outcomes of full size and reduced DCD grafts in terms of incidence of complications as well as survival of both recipients and grafts. Methods This is a retrospective review of PLTs using DCD grafts. Patients were divided into those who received full or reduced grafts. Data was collected for comparison of pre-transplant recipient parameters, donor parameters, operative parameters, post-transplant recipient parameters and outcomes. Laboratory markers were checked at discharge, 1- and 5-years post-transplant. Results 14 PLTs from DCD donors between 2005 and 2018 were identified; 9 full size and 5 reduced grafts. Donors of both groups were Maastricht category III donors. Functional warm ischemia time did not show significant difference while cold ischemia time was significantly longer in reduced graft group. Recipients of full grafts were significantly older, heavier in weight and tend to wait significantly longer on transplant waiting list. The main indications for PLT were biliary atresia and Alpha-1 anti-trypsin deficiency. Recipients of reduced grafts were sicker pre-transplant. Post-transplant hospital and PICU stay were longer in the reduced group but this was not significant. Only significant laboratory difference was at 1-year post-transplant as albumen and creatinine were significantly higher in the full graft group while ALT was significantly higher in the reduced graft group. There was no significant difference between two groups in terms of long-term complications. 3 patients in each group survived more than 5 years post-transplant. one child was re-transplanted in the reduced group due to portal vein thrombosis, this patient received another DBD graft then unfortunately died due to liver failure. One child from full graft group also died from a non-graft related cause (figures 1, 2). Summary 14 PLTs from DCD grafts (9 full and 5 reduced) were identified. Recipients of full grafts were older and heavier while reduced graft recipients were sicker in the pre-transplant period. Both groups demonstrated comparable graft and patient survival as well as long-term complications rates. Conclusion Selected DCD grafts are potential source to widen the graft pool in children

Purpose of review To summarize key studies in liver preservation published over the last 3 years and evaluate benefits and limitations of the different perfusion techniques. Selected experimental applications that may be translated to the clinical use will be also discussed. Recent findings Normothermic machine perfusion (NMP) has transitioned into clinical practice. Viability assessment is a reliable tool for clinical decision-making, and safety of the back-to-base approach has facilitated adoption of the technology. Data supporting well tolerated use of declined livers after NMP and new protocols selecting complex recipients aim to improve access to suitable organs. Hypothermic machine perfusion (HMP) is showing promising clinical results by decreasing biliary complications in recipients' receiving organs donated after circulatory death (DCD) and improving early graft function in extended criteria organs. Long-term data of HMP on DCD livers shows improved graft survival over standard SCS. Novel approaches utilizing sequential HMP--NMP or ischaemia-free preservation aim to improve outcomes of extended criteria organs. Summary Machine perfusion for organ transplantation has become an established technique but the field is rapidly evolving. Ongoing research focuses on evaluation of the intervention efficacy and finding optimal indications to use each perfusion strategy according to graft type and clinical scenario.

Background:Ex situ donor liver machine perfusion is a promising tool to assess organ viability prior to transplantation and platform to investigate novel therapeutic interventions. However, the wide variability in donor and graft characteristics between individual donor livers limits the comparability of results. We investigated the hypothesis that the development of a split liver ex situ machine perfusion protocol provides the ideal comparative controls in the investigation of machine perfusion techniques and therapeutic interventions, thus leading to more comparable results.Methods: Four discarded human donor livers were surgically split following identification and separation of right and left inflow and outflow vessels. Each lobe, on separate perfusion machines, was subjected to normothermic perfusion using an artificial hemoglobin-based oxygen carrier solution for 6 h. Metabolic parameters as well as hepatic artery and portal vein perfusion parameters monitored.Results: Trends in hepatic artery and portal vein flows showed a general increase in both lobes throughout each perfusion experiment, even when normalized for tissue weight. Progressive decreases in perfusate lactate and glucose levels exhibited comparable trends in between lobes.Conclusion: Our results demonstrate comparability between right and left lobes when simultaneously subjected to normothermic machine perfusion. In the pre-clinical setting, this model provides the ideal comparative controls in the investigation of therapeutic interventions.

After major bile duct injury, hepaticojejunostomy can result in good long-term patency, but anastomotic stricture is a common cause of long-term morbidity. There is a need to assimilate high-level evidence to establish risk factors for development of anastomotic stricture after hepaticojejunostomy for bile duct injury.A systematic review of studies reporting the rate of anastomotic stricture after hepaticojejunostomy for bile duct injury was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Meta-analyses of proposed risk factors were then performed.Meta-analysis included 5 factors (n = 2,155 patients, 17 studies). Concomitant vascular injury (odds ratio 4.96; 95% confidence interval 1.92-12.86; P = .001), postrepair bile leak (odds ratio: 8.03; 95% confidence interval 2.04-31.71; P = .003), and repair by nonspecialist surgeon (odds ratio 11.29; 95% confidence interval 5.21-24.47; P.0001) increased the rate of anastomotic stricture of hepaticojejunostomy after bile duct injury. Level of injury according to the Strasberg Grade did not significantly affect the rate of anastomotic stricture (odds ratio: 0.97; 95% confidence interval 0.45-2.10; P = .93). Owing to heterogeneity of reporting, it was not possible to perform a meta-analysis for the impact of timing of repair on anastomotic stricture rate.The only modifiable risk factor, repair by a nonspecialist surgeon, demonstrates the importance of broad awareness of these data. Knowledge of these risk factors may permit risk stratification of follow-up, better informed consent, and understanding of prognosis.

BACKGROUND The International Study Group on Pancreatic Surgery recommends upfront surgery for resectable pancreatic cancer or borderline resectable-venous (BR-V) disease and neoadjuvant therapy (NAT) among those with arterial involvement (BR-A or locally advanced, LA). Though neoadjuvant therapy (NAT) is a promising strategy, outcomes are rarely reported on intention-to-treat (ITT) basis. This study presents ITT outcomes where pathways to surgery were in line with International Study Group on Pancreatic Surgery guidelines. METHODS Patients recommended for potentially curative treatment with PDAC between 2012 and 2017 (n = 345) were classified as resectable, BR-A/BR-V or LA, according to NCCN criteria. The primary outcome was overall survival. Secondary outcomes were resection rates, positive margins and toxicity among patients receiving NAT. RESULTS At surgery, the resection rates were 78% (172/221), 65% (35/54) and 54% (21/39) for those with resectable, BR-V and BR-A/LA disease, respectively (P

Background The liver-first approach in patients with synchronous colorectal liver metastases (CRLM) has gained wide consensus but its role is still to be clarified. We aimed to elucidate the outcome of the liver-first approach and to identify patients who benefit at most from this approach. Methods Patients with synchronous CRLM included in the LiverMetSurvey registry between 2000 and 2017 were considered. Three strategies were analyzed, i.e. liver-first approach, colorectal resection followed by liver resection (primary-first), and simultaneous resection, and three groups of patients were analyzed, i.e. solitary metastasis, multiple unilobar CRLM, and multiple bilobar CRLM. In each group, patients from the three strategy groups were matched by propensity score analysis. Results Overall, 7360 patients were analyzed: 4415 primary-first, 552 liver-first, and 2393 simultaneous resections. Compared with the other groups, the liver-first group had more rectal tumors (58.0% vs. 31.2%) and higher hepatic tumor burden (more than three CRLMs: 34.8% vs. 24.0%; size > 50 mm: 35.6% vs. 22.8%; p < 0.001). In patients with solitary and multiple unilobar CRLM, survival was similar regardless of treatment strategy, whereas in patients with multiple bilobar metastases, the liver-first approach was an independent positive prognostic factor, both in unmatched patients (3-year survival 65.9% vs. primary-first 60.4%: hazard ratio [HR] 1.321, p = 0.031; vs. simultaneous resections 54.4%: HR 1.624, p < 0.001) and after propensity score matching (vs. primary-first: HR 1.667, p = 0.017; vs. simultaneous resections: HR 2.278, p = 0.003). Conclusion In patients with synchronous CRLM, the surgical strategy should be decided according to the hepatic tumor burden. In the presence of multiple bilobar CRLM, the liver-first approach is associated with longer survival than the alternative approaches and should be evaluated as standard.

This review article focuses on current clinical outcomes with novel perfusion strategies in organ transplantation. Broadly, these approaches can be divided into in situ regional perfusion in the donor and ex situ machine perfusion of individual organs. In both settings, hypothermic and normothermic techniques are in clinical use. Evidence from full text articles, abstracts, and data presented at scientific meetings has been considered. Animal studies have been excluded. The review focuses on kidney, liver, pancreas, heart, and lungs. The level of evidence ranges from quasi-experimental work in human pancreas to multiple meta-analyses of Randomized Controlled Trials for hypothermic machine perfusion of kidneys. The data in this review were presented to experts in organ perfusion and preservation at the National Health Service Blood and Transplant Preservation and Perfusion Future Strategy Summit in London in October 2018. The outcomes of the meeting are discussed in the review after due consideration of the available evidence base.