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Competing Interests: I declare no competing interests.

Background and Aims: Identifying international differences in utilization and outcomes of liver transplantation (LT) after donation after circulatory death (DCD) donation provides a unique opportunity for benchmarking and population-level insight., Methods: Adult (≥18 years) LT data between 2008 and 2018 from the UK and US were used to assess mortality and graft failure after DCD LT. We used time-dependent Cox-regression methods to estimate hazard ratios (HR) for risk-adjusted short-term (0-90 days) and longer-term (90 days-5 years) outcomes., Results: One-thousand five-hundred-and-sixty LT receipts from the UK and 3426 from the US were included. Over the study period, the use of DCD livers increased from 15.7% to 23.9% in the UK compared to 5.1% to 7.6% in the US. In the UK, DCD donors were older (UK:51 vs. US:33 years) with longer cold ischaemia time (UK: 437 vs. US: 333 min). Recipients in the US had higher Model for End-stage Liver Disease (MELD) scores, higher body mass index, higher proportions of ascites, encephalopathy, diabetes and previous abdominal surgeries. No difference in the risk-adjusted short-term mortality or graft failure was observed between the countries. In the longer-term (90 days-5 years), the UK had lower mortality and graft failure (adj.mortality HR:UK: 0.63 (95% CI: 0.49-0.80); graft failure HR: UK: 0.72, 95% CI: 0.58-0.91). The cumulative incidence of retransplantation was higher in the UK (5 years: UK: 11.9% vs. 4.6%; p < .001)., Conclusions: For those receiving a DCD LT, longer-term post-transplant outcomes in the UK are superior to the US, however, significant differences in recipient illness, graft quality and access to retransplantation were seen between the two countries., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Interest has revived in the use of hepatic arterial infusion chemotherapy (HAIC) for intermediate-advanced hepatocellular carcinoma (HCC) while transarterial chemoembolization (TACE) has been a longstanding loco-regional therapy. Aim: We conducted a systematic review and meta-analysis of patients with unresectable HCC treated with HAIC or TACE to look for differences in survival, adverse events, mortality and downstaging. Methods: All studies published before 29 July 2022 were identified by searching PubMed, Embase, Web of Science and Cochrane Library databases for patients with unresectable HCC and received HAIC or TACE as initial treatment. Data extracted from studies was statistically analysed using RevMan5.3 software. Results: A total of one randomized controlled trial (RCT) and 7 cohort studies (5 retrospective, 2 prospective) including 1,060 (TACE group: 534, HAIC group: 526) patients were screened. Compared with the TACE group, patients who received HAIC as initial therapy had better overall survival (OS) (HR = 0.53, 95%CI [0.40, 0.69]) and progression-free survival (PFS) (HR = 0.54, 95%CI [0.40, 0.72]). Further subgroup analysis revealed that HAIC showed priority over TACE on prognosis outcome regardless of tumour stage, especially in patients with advanced portal vein tumour thrombus (PVTT). Utilization of port system will not boost the efficacy of HAIC whereas using a replaced-microcatheter for each procedure could better reduce the progressive disease (PD) rate (RR = 0.55, 95%CI [0.40, 0.76]). The pooled RR favoured the HAIC group with regard to partial response (PR) (RR = 2.87, 95%CI [2.18, 3.78]) and this was validated by both GRADE summary and trial sequential analysis. The rate of resection after treatment was higher in the HAIC group (RR = 2.37, 95%CI [1.54, 3.66]), whilst no difference was found with procedure-related mortality (RR = 0.56, 95%CI [0.13, 2.38]) between two groups. Compared with the traditional chemotherapy regimen (fluorouracil/leucovorin/oxaliplatin) FOLFOX-HAIC appears to be better in improving the treatment efficacy. Conclusion: Patients with unresectable HCC could potentially benefit more from HAIC rather than standard TACE treatment. A re-evaluation of HAIC as a treatment option in intermediate and advanced HCC is warranted., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Si, Huang, Khorsandi, Ma and Heaton.)

Background: This study aimed to assess the differences between the United States and the United Kingdom in the characteristics and posttransplant survival of patients who received donation after circulatory death (DCD) liver allografts from donors aged >60 y., Methods: Data were collected from the UK Transplant Registry and the United Network for Organ Sharing databases. Cohorts were dichotomized into donor age subgroups (donor >60 y [D >60]; donor ≤60 y [D ≤60]). Study period: January 1, 2001, to December 31, 2015., Results: 1157 DCD LTs were performed in the United Kingdom versus 3394 in the United States. Only 13.8% of US DCD donors were aged >50 y, contrary to 44.3% in the United Kingdom. D >60 were 22.6% in the United Kingdom versus 2.4% in the United States. In the United Kingdom, 64.2% of D >60 clustered in 2 metropolitan centers. In the United States, there was marked inter-regional variation. A total of 78.3% of the US DCD allografts were used locally. One- and 5-y unadjusted DCD graft survival was higher in the United Kingdom versus the United States (87.3% versus 81.4%, and 78.0% versus 71.3%, respectively; P < 0.001). One- and 5-y D >60 graft survival was higher in the United Kingdom (87.3% versus 68.1%, and 77.9% versus 51.4%, United Kingdom versus United States, respectively; P < 0.001). In both groups, grafts from donors ≤30 y had the best survival. Survival was similar for donors aged 41 to 50 versus 51 to 60 in both cohorts., Conclusions: Compared with the United Kingdom, older DCD LT utilization remained low in the United States, with worse D >60 survival. Nonetheless, present data indicate similar survivals for older donors aged ≤60, supporting an extension to the current US DCD age cutoff., Competing Interests: The authors declare no funding or conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The Risk Estimation of Tumor Recurrence After Transplant (RETREAT) score as a prognostic index for recurrence has been reported previously and has not been validated outside the USA. Our study has validated the score in a single center UK cohort of patients being transplanted for HCC., Methods: LT for HCC between 2008 and 2018 at our center were analyzed. Recurrence-free survival (RFS) was compared by the RETREAT score and validated using Net Reclassification Improvement (NRI) by comparing it to Milan criteria., Results: 346 adult HCC patients were transplanted of whom 313 were included. 28 (8.9%) had a recurrence. Summation of largest diameter and total number of viable tumors (HR = 1.19, p < 0.001), micro-/macro-vascular invasion (HR = 3.74, p = 0.002) and AFP>20 ng/ml (HR = 3.03, p = 0.005) were associated with recurrence on multivariate analysis. RFS decreased with increasing RETREAT score (log-rank p = 0.016). RETREAT performed better than Milan with significant NRI at 1- and 2-years post-transplant (0.43 (p = 0.004) and 0.38 (p = 0.03) respectively)., Conclusion: LT outcomes using the revised UK criteria are equivalent to Milan criteria. Further, RETREAT score was validated as a prognostic index for the first time in a UK cohort and may assist risk stratification, selection for adjuvant therapies and guide surveillance., (Crown Copyright © 2021. Published by Elsevier Ltd. All rights reserved.)

Altered metabolism is a defining hallmark of cancer. Metabolic adaptations are often linked to a reprogramming of the mitochondria due to the importance of these organelles in energy production and biosynthesis. Cancer cells present heterogeneous metabolic phenotypes that can be modulated by signals originating from the tumor microenvironment. Extracellular vesicles (EVs) are recognized as key players in intercellular communications and mediate many of the hallmarks of cancer via the delivery of their diverse biological cargo molecules. Firstly, this review introduces the most characteristic changes that the EV-biogenesis machinery and mitochondria undergo in the context of cancer. Then, it focuses on the EV-driven processes which alter mitochondrial structure, composition, and function to provide a survival advantage to cancer cells in the context of the hallmarks of cancers, such as altered metabolic strategies, migration and invasiveness, immune surveillance escape, and evasion of apoptosis. Finally, it explores the as yet untapped potential of targeting mitochondria using EVs as delivery vectors as a promising cancer therapeutic strategy.

Background: Advancements based on artificial intelligence have emerged in all areas of medicine. Many decisions in organ transplantation can now potentially be addressed in a more precise manner with the aid of artificial intelligence., Method/results: All elements of liver transplantation consist of a set of input variables and a set of output variables. Artificial intelligence identifies relationships between the input variables; that is, how they select the data groups to train patterns and how they can predict the potential outcomes of the output variables. The most widely used classifiers to address the different aspects of liver transplantation are artificial neural networks, decision tree classifiers, random forest, and naïve Bayes classification models. Artificial intelligence applications are being evaluated in liver transplantation, especially in organ allocation, donor-recipient matching, survival prediction analysis, and transplant oncology., Conclusion: In the years to come, deep learning-based models will be used by liver transplant experts to support their decisions, especially in areas where securing equitability in the transplant process needs to be optimized., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Cholangiocarcinoma is a form of hepatobiliary cancer with an abysmal prognosis. Despite advances in our understanding of cholangiocarcinoma pathophysiology and its genomic landscape, targeted therapies have not yet made a significant impact on its clinical management. The low response rates of targeted therapies in cholangiocarcinoma suggest that patient heterogeneity contributes to poor clinical outcome. Here we used mass spectrometry-based phosphoproteomics and computational methods to identify patient-specific drug targets in patient tumors and cholangiocarcinoma-derived cell lines. We analyzed 13 primary tumors of patients with cholangiocarcinoma with matched nonmalignant tissue and 7 different cholangiocarcinoma cell lines, leading to the identification and quantification of more than 13,000 phosphorylation sites. The phosphoproteomes of cholangiocarcinoma cell lines and patient tumors were significantly correlated. MEK1, KIT, ERK1/2, and several cyclin-dependent kinases were among the protein kinases most frequently showing increased activity in cholangiocarcinoma relative to nonmalignant tissue. Application of the Drug Ranking Using Machine Learning (DRUML) algorithm selected inhibitors of histone deacetylase (HDAC; belinostat and CAY10603) and PI3K pathway members as high-ranking therapies to use in primary cholangiocarcinoma. The accuracy of the computational drug rankings based on predicted responses was confirmed in cell-line models of cholangiocarcinoma. Together, this study uncovers frequently activated biochemical pathways in cholangiocarcinoma and provides a proof of concept for the application of computational methodology to rank drugs based on efficacy in individual patients. SIGNIFICANCE: Phosphoproteomic and computational analyses identify patient-specific drug targets in cholangiocarcinoma, supporting the potential of a machine learning method to predict personalized therapies., (©2021 The Authors; Published by the American Association for Cancer Research.)

Introduction: Hepatocellular carcinoma (HCC) is the most common primary liver cancer with a low 5-year survival rate. The heterogeneity of HCC makes monotherapy unlikely. The development of diagnostic programs and new treatments targeting common genetic events in the carcinogenic process are providing further insights into the management of HCC. The aim of this study was firstly to validate key genes that are involved in promoting HCC development and as biomarkers for early diagnosis and, secondly, to define their links with antitumor immunity including inhibitory checkpoints., Methods: Multiple databases including Gene Expression Omnibus (GEO), Gene Expression Profiling Interactive Analysis (GEPIA), Kaplan-Meier Plotter, UALCAN, and Oncomine were used for target gene screening and establishment of a co-expression network. Clinical data and RNAseq of 367 HCC patients were downloaded from the Cancer Genome Atlas (TCGA) database. The diagnostic and prognostic value of screened genes were tested by receiver operating characteristic (ROC) curve and correlation analysis. The links with the key genes in HCC and antitumor immunity were defined using both blood and liver tissue collected prospectively from HCC patients in our center., Results: Upregulation of CCNB1, CDC20, and CENPF was commonly observed in HCC and are involved in the p53 signal pathway. The hepatic mRNA expression levels of these three genes were strongly associated with patients' prognosis and expressed high value of area under the ROC curve (AUC). Further analysis revealed that these three genes were positively correlated with the gene expression levels of IFN-γ, TNF-α, and IL-17 in peripheral blood. In addition, the expression of CENPF showed positive correlation with the percentage of CD8 pos T cells and negative correlation with the percentage of CD4 pos T cells in the peripheral blood. In the HCC microenvironment, the transcript levels of these three genes and inhibitory checkpoint molecules including PD-1, CTLA-4, and TIM-3 were positively correlated., Conclusion: The upregulation of CCNB1, CDC20, and CENPF genes was a common event in hepatocarcinogenesis. Expression levels of CCNB1, CDC20, and CENPF showed potential for early diagnosis and prediction of prognosis in HCC patients. There is a close association between three genes and Th1/Th17 cytokines as well as the count of CD4 pos and CD8 pos T cells. The positive correlation between the three genes and inhibitory checkpoint genes, PD-1, CTLA-4, and TIM-3, indicates that these genes are linked with weakened antitumor immunity in HCC. Our findings may provide further insights into developing novel therapies for HCC., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Si, Huang, Jiang, Walker-Jacobs, Gill, Hegarty, Hamza, Khorsandi, Jassem, Heaton and Ma.)

The aim of the study was to assess the UK donation after circulatory death (DCD) liver transplant experience from donors ≥70 years. Nationwide UK DCD retrospective analysis was conducted between 2001 and 2015 (n = 1163). Recipients were divided into group 1 vs. group 2 (donors 70≥ vs. <70 years, respectively). group 1 (n = 69, 5.9%) recipients were older (median 59 vs. 55 years, p = .001) and had longer waitlist time (128 vs. 84 days; p = .039). 94.2% of group 1 clustered in London and Birmingham, where the two busiest centers are located. group 1 allografts had higher UKDRI and UK DCD Risk Scores but similar WIT and CIT and were more likely to have been imported. Both groups had similar 1-, 3-, and 5-year graft survival (group 1, 90%, 81.4%, and 74% vs. group 2, 88.6%, 81.4%, and 78.6%, respectively; p = .54). Both groups had similar ICU stay length (p = .22), 3-month hepatic artery thrombosis rates (4.4% vs 4.0%; p = .9), and 12-month readmission rates for all biliary complications (20.3% vs 25.7%; p = .32). This study demonstrates that acceptable outcomes are achievable using older grafts in a highly selected cohort at experienced centers. Advanced age should not be an absolute contraindication to utilizing a DCD graft from donors aged ≥70 years., (© 2020 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Background: We report our experience of treating anastomotic strictures using a novel type of fully covered metal stent (FCSEMS). This stent, known as the Kaffes Stent, is short-length with an antimigration waist and is easily removable due to long retrieval wires deployed within the duodenum., Methods: Sixty-two patients underwent ERCP and Kaffes stent insertion for post-transplant anastomotic strictures following confirmation of a stricture on MRCP. These patients were retrospectively analysed for immediate and long-term stricture resolution, improvement in symptoms and liver function tests (LFTs), stricture recurrence and complication rates., Results: Of the 56 patients who had their stent removed at the time of analysis, 54 (96%) had immediate stricture resolution and 42 continued to have long-term resolution (mean follow-up period was 548 days). Of the 16 patients with symptoms of biliary obstruction, 13 had resolution of their symptoms. Overall, there was a significant improvement in LFTs after stent removal compared to before stent insertion. Complication rates were 15% with only one patient requiring biliary reconstruction., Conclusions: The Kaffes stent is effective and safe at resolving post liver transplant biliary anastomotic strictures.

Background: Acute kidney injury (AKI) after liver transplantation (LT) is a common problem with complex management. The aims were to analyze the profile of AKI-RIFLE categories in the post-transplant setting of a wide multicentre cohort of patients in the MELD era and to specifically determine the effect of tacrolimus-based (TACRO) immunosuppressive regimes on the development of AKI., Methods: A retrospective analysis of 550 (2007-2012) consecutive patients transplanted at Reina Sofia, Cordoba, and King's College Hospital, London, was performed. Inclusion criterion was to have CNI as part of initial immunosuppression immediately after LT., Results: After exclusion criteria, a total of 477 patients were analyzed. Incidence of AKI within the first 2 weeks after LT was 65.8% (AKI-Risk), 41.3% (AKI-Injury), and 12.3% (AKI-Failure). The development of any type of AKI had no impact on short- and/or long-term survival up to 3 years after the transplant. Moreover, AKI was almost universal in the early post-transplant period and TACRO trough concentrations during the first 2 weeks after the transplant were not predictors of AKI in none of its categories in the multivariate analyses., Conclusions: Low-TACRO-based regimes were not as useful as expected in the prevention of AKI when analyzed in the context of a large contemporary LT series., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Coronavirus disease 2019 (COVID-19) caused by a novel coronavirus called severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is driving a present day global pandemic. Immunosuppressed patients are regarded as a high-risk cohort. The following is a short report on COVID-19 in liver transplant recipients (n = 5) from a high volume UK liver transplant unit with a large follow-up cohort (n = 4500). Based on this limited data, liver transplant recipients appear to have a low incidence of COVID-19, with less severe symptoms than expected, when compared with the general population and other solid organ recipients. This possibly could be related to self-isolation adherence and/or the 'ideal' level of immunosuppression that favourably modulates the immune response to COVID-19., (© 2020 The Authors. Liver International published by John Wiley & Sons Ltd.)

Thyroid hormones are regarded as the major controllers of metabolic rate and oxygen consumption in mammals. Although it has been demonstrated that thyroid hormone supplementation improves bovine embryo development in vitro, the cellular mechanisms underlying these effects are so far unknown. In this study, we investigated the role of thyroid hormone in development of human preimplantation embryos. Embryos were cultured in the presence or absence of 10 -7  M triiodothyronine (T3) till blastocyst stage. Inner cell mass (ICM) and trophectoderm (TE) were separated mechanically and subjected to RNAseq or quantification of mitochondrial DNA copy number. Analyses were performed using DESeq (v1.16.0 on R v3.1.3), MeV4.9 and MitoMiner 4.0 v2018 JUN platforms. We found that the exposure of human preimplantation embryos to T3 had a profound impact on nuclear gene transcription only in the cells of ICM (1178 regulated genes-10.5% of 11 196 expressed genes) and almost no effect on cells of TE (38 regulated genes-0.3% of expressed genes). The analyses suggest that T3 induces in ICM a shift in ribosome and oxidative phosphorylation activity, as the upregulated genes are contributing to the composition and organization of the respiratory chain and associated cofactors involved in mitoribosome assembly and stability. Furthermore, a number of genes affecting the citric acid cycle energy production have reduced expression. Our findings might explain why thyroid disorders in women have been associated with reduced fertility and adverse pregnancy outcome. Our data also raise a possibility that supplementation of culture media with T3 may improve outcomes for women undergoing in vitro fertilization., (©2019 The Authors. Stem Cells published by Wiley Periodicals, Inc. on behalf of AlphaMed Press 2019.)

Objective: Hepatocellular carcinoma (HCC) is a complication of the common genetic condition hereditary hemochromatosis (HH). It is unknown whether HH as an etiology of liver disease impacts the outcome. We compared the results of liver transplantation (LT), surgical resection and locoregional therapies in a matched cohort study and investigated whether HH as an etiology has an impact on survival., Materials and Methods: Consecutive patients with HH and HCC (2000 to 2015) were compared with age, sex and Barcelona Clinic Liver Cancer (BCLC) stage-matched non-HH HCC cases. Patients were offered curative or noncurative treatment according to BCLC stage and Milan criteria. The primary endpoint was all-cause mortality., Results: A total of 102 patients (52 HH; total cohort median age: 67 [44 to 78] y, 97% male, Model for End-stage Liver Disease: 9 [5 to 31]) were studied with a median follow-up of 22 (3 to 126) months. Of the HH cases, the median serum ferritin at diagnosis of HCC was 326 (27 to 5718) μg/L and α-fetoprotein 33 (2 to 197,926) kIU/L. Five-year survival for HH patients receiving curative therapy was 77% (80% for LT, 67% for resection/radiofrequency ablation), and 15% (23% for transarterial chemoembolization) for those undergoing noncurative therapy. Survival for HH patients compared with controls was similar (hazard ratio=0.949; P=0.839). On multivariate Cox regression survival analysis, BCLC stage, and diagnosis of ischemic heart disease (but not HH diagnosis) were independently associated with reduced survival., Conclusions: Patients with HCC and HH can achieve comparable survival rates following curative or LRT modalities to other liver diseases. The BCLC staging system accurately stratifies survival and excellent 5-year survival is possible following LT in selected patients.

Liver transplantation (LT) for small infants remains challenging because of the demands related to graft selection, surgical technique, and perioperative management. The aim of this study was to evaluate the short-term and longterm outcomes of LT regarding vascular/biliary complications, renal function, growth, and patient/graft survival in infants ≤3 months compared with those of an age between >3 and 6 months at a single transplant center. A total of 64 infants ≤6 months underwent LT and were divided into 2 groups according to age at LT: those of age ≤3 months (range, 6-118 days; XS group, n = 37) and those of age >3 to ≤6 months (range, 124-179 days; S group, n = 27) between 1989 and 2014. Acute liver failure was the main indication for LT in the XS group (n = 31, 84%) versus S (n = 7, 26%). The overall incidence of hepatic artery thrombosis and portal vein thrombosis/stricture were 5.4% and 10.8% in the XS group and 7.4% and 11.1% in the S group, respectively (not significant). The overall incidence of biliary stricture and leakage were 5.4% and 2.7% in the XS group and 3.7% and 3.7% in the S group, respectively (not significant). There was no significant difference between the 2 groups in terms of renal function. No significant difference was found between the 2 groups for each year after LT in terms of height and weight z score. The 1-, 5-, and 10-year patient survival rates were 70.3%, 70.3%, and 70.3% in the XS group compared with 92.6%, 88.9%, and 88.9% in the S group, respectively (not significant). In conclusion, LT for smaller infants has acceptable outcomes despite the challenges of surgical technique, including vascular reconstruction and graft preparation, and perioperative management., (Copyright © 2019 The Authors. Liver Transplantation published by Wiley Periodicals, Inc., on behalf of American Association for the Study of Liver Diseases.)

Objectives: Aim of the study was to assess the effect of economic recession on organ donation and transplantation in Greece., Methods: Retrospective data (2002-2016) provided by the Hellenic Transplant Organization (HTO), International Registry in Organ Donation and Transplantation, Eurotransplant, Scandiatransplant, National Health Service Blood and Transplant (NHSBT), and United Network of Organ Sharing (UNOS) databases were analyzed. HTO database was divided into the precrisis (2002-2008) and crisis (2009-2016) era. Donation and transplantation rates between the two periods were compared. Trend estimation analysis was applied on the latter period., Results: Since 2009, organ donation significantly declined without significant change in the reported brain deaths. Overall solid organ transplantations decreased (319.63 ± 70.4 from 460 ± 55.25 transplants/year, P = 0.001). Kidney transplantation rates declined (139.38 ± 29.7 from 209.43 ± 20.9 transplants/year, P = 0.000), with dramatic reduction in both deceased (99 ± 27.5 from 136.43 ± 131.4 transplants/year, P = 0.030) and living donor kidney transplantations (40.38 ± 6.1 from 73 ± 12.5 transplants/year, P = 0.000). Liver, heart, and lung transplant rates were not significantly affected; however, they have been low throughout both periods. Convertion to donation has not been affected by the crisis. Time series logistic regression of the crisis period demonstrated declining trends in organ donation, total solid organ transplantation, and deceased donor kidney, liver, and lung transplantation. In 2015, Greek organ donation rates were inferior to Eurotransplant, Scandiatransplant, NHSBT, UNOS, and Italy., Conclusions: There has been a temporal correlation between the economic recession and organ donation and transplantation crisis in Greece. Irrespective of the cause, measures should be taken to reverse this in order to avert the increased morbidity and mortality on the transplant waiting list., (Copyright © 2018 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.)

Neonatal livers are a potential source of good-quality hepatocytes for clinical transplantation. We compared viability and function of neonatal hepatocytes (NHs) and adult hepatocytes (AHs) and report their clinical use both intraportally and in alginate microbeads. Following isolation from donor livers, hepatocyte function was assessed using albumin, alpha-1-antitrypsin, and factor VII. Metabolic function was investigated by measuring resorufin conjugation, ammonia metabolism, uridine diphosphate glucuronosyltransferase enzyme activity, and cytochrome P450 (CYP) function following induction. Activation of the instant blood-mediated inflammatory reaction by NHs and AHs was investigated using an in vitro blood perfusion model, and tissue factor expression was analyzed using real-time polymerase chain reaction (RT-PCR). Clinical hepatocyte transplantation (HT) was undertaken using standard protocols. Hepatocytes were isolated from 14 neonatal livers, with an average viability of 89.4% ± 1.8% (mean ± standard error of the mean) and average yield of 9.3 × 10 6 ± 2.0 × 10 6 cells/g. Hepatocytes were isolated from 14 adult livers with an average viability of 78.6% ± 2.4% and yield 2.2 × 10 6 ± 0.5 × 10 5 cells/g. NHs had significantly higher viability after cryopreservation than AHs, with better attachment efficiency and less plasma membrane leakage. There were no differences in albumin, alpha-1-antitrypsin, and factor VII synthesis between NHs and AHs (P > 0.05). Neonatal cells had inducible phase 1 enzymes as assessed by CYP function and functional phase 2 enzymes, in which activity was comparable to AHs. In an in vitro blood perfusion model, AHs elicited increased thrombus formation with a greater consumption of platelets and white cells compared with NHs (28.3 × 10 9 versus 118.7 × 10 9 and 3.3 × 10 9 versus 6.6 × 10 9 ; P < 0.01). Intraportal transplantation and intraperitoneal transplantation of alginate encapsulated hepatocytes was safe, and preliminary data suggest the cells may activate the immune response to a lesser degree than adult cells. In conclusion, we have shown NHs have excellent cell viability, function, and drug metabolism making them a suitable alternative source for clinical HT. Liver Transplantation 24 394-406 2018 AASLD., (© 2018 by the American Association for the Study of Liver Diseases.)

Mitochondria have their own genomic, transcriptomic and proteomic machinery but are unable to be autonomous, needing both nuclear and mitochondrial genomes. The aim of this work was to use computational biology to explore the involvement of Mitochondrial microRNAs (MitomiRs) and their interactions with the mitochondrial proteome in a clinical model of primary non function (PNF) of the donor after cardiac death (DCD) liver. Archival array data on the differential expression of miRNA in DCD PNF was re-analyzed using a number of publically available computational algorithms. 10 MitomiRs were identified of importance in DCD PNF, 7 with predicted interaction of their seed sequence with the mitochondrial transcriptome that included both coding, and non coding areas of the hypervariability region 1 (HVR1) and control region. Considering miRNA regulation of the nuclear encoded mitochondrial proteome, 7 hypothetical small proteins were identified with homolog function that ranged from co-factor for formation of ATP Synthase, REDOX balance and an importin/exportin protein. In silico, unconventional seed interactions, both non canonical and alternative seed sites, appear to be of greater importance in MitomiR regulation of the mitochondrial genome. Additionally, a number of novel small proteins of relevance in transplantation have been identified which need further characterization.

The following is a short report on the use of a heterozygous (PiMZ) alpha 1 antitrypsin (α1AT) living related donor liver in a homozygous (PiZ) child that was complicated by massive ascites early after transplant. This clinical report is then followed by a brief summary of present knowledge on the α 1 AT protein and management of massive ascites in the pediatric liver transplant recipient., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: Donor liver function in transplantation is defined by mitochondrial function and the ability of mitochondria to recover from the sequence of warm and/or cold ischemia. Mitochondrial resilience maybe related to assembly and- subunit composition of Complex 1. The aim of this study was to determine if Complex 1 subunit composition was different in donor livers of varying quality and whether oxygen exposure had any effect., Results: Five human livers not suitable for transplant were split. One half placed in cold static storage and the other half exposed to 40% oxygen for 2 h. Protein was extracted for western blot. Membranes were probed with antibodies against β-actin and the following subunits of Complex 1: MTND1, NDUFA10, NDUFB6 and NDUFV2. No difference in steady state Complex 1 subunit composition was demonstrated between donor livers of varying quality, in terms of steatosis or mode of donation. Neither did exposure to oxygen influence Complex 1 subunit composition. This small observational study on subunit levels suggest that Complex 1 is fully assembled as no degradation of subunits associated with the different parts of the enzyme was seen.

BACKGROUND This is the largest UK-based study on the effect of recipient body mass index (BMI) and its extremes (BMI <18.5 and BMI ≥35 kg/m²) on liver transplant (LT) outcomes. Its purpose was to analyze the BMI effect on post-LT mortality, graft loss, primary non-function (PNF), and graft vascular and biliary complications. MATERIAL AND METHODS Data were retrieved from a single-center LT database of 2,115 consecutive patients receiving first LT during period February 2004 to September 2015. Survivals were compared across the BMI groups; the effects of recipient BMI on survival, PNF, and graft vascular and biliary complications were analyzed via regression. RESULTS Autoimmune disease and nonalcoholic steatohepatitis were prevalent among underweight and morbidly obese adults, respectively. Graft survival was similar across BMI classes at 30 days and in 1, 2, 5, and 10 years (p=0.75) and on obese versus non-obese (p=0.33). BMI <35 kg/m² versus BMI ≥35 kg/m² mean graft survival was similar (p=0.84). BMI <18.5 kg/m² recipients tended to have inferior mean graft and patient survivals; however, the difference was non-significant (p=0.09 and p=0.1 respectively). BMI <18.5 kg/m² recipients were at higher risk of hepatic artery thrombosis (HR, 1.73, 95% CI 1.73-3, p<0.05). Adult underweight status was an independent HAT risk factor (HR 3, 95% CI 1-8.6, p=0.046). BMI class did not affect ischemic cholangiopathy risk (p=0.84). However, the overall biliary complication risk increased by 3% for every 1 kg/m² BMI rise. CONCLUSIONS Post-LT survival is independent of recipient BMI. Underweight status is linked to higher HAT risk. Biliary complication risk increases with rising recipient BMI. After appropriate recipient selection, recipient BMI extremes are not a contraindication for LT.

Aim: To identify objective predictive factors for donor after cardiac death (DCD) graft loss and using those factors, develop a donor recipient stratification risk predictive model that could be used to calculate a DCD risk index (DCD-RI) to help in prospective decision making on organ use., Methods: The model included objective data from a single institute DCD database (2005-2013, n = 261). Univariate survival analysis was followed by adjusted Cox-regressional hazard model. Covariates selected via univariate regression were added to the model via forward selection, significance level P = 0.3. The warm ischemic threshold was clinically set at 30 min. Points were given to each predictor in proportion to their hazard ratio. Using this model, the DCD-RI was calculated. The cohort was stratified to predict graft loss risk and respective graft survival calculated., Results: DCD graft survival predictors were primary indication for transplant ( P = 0.066), retransplantation ( P = 0.176), MELD > 25 ( P = 0.05), cold ischemia > 10 h ( P = 0.292) and donor hepatectomy time > 60 min ( P = 0.028). According to the calculated DCD-RI score three risk classes could be defined of low (DCD-RI < 1), standard (DCD-RI 2-4) and high risk (DCD-RI > 5) with a 5 years graft survival of 86%, 78% and 34%, respectively., Conclusion: The DCD-RI score independently predicted graft loss ( P < 0.001) and the DCD-RI class predicted graft survival ( P < 0.001)., Competing Interests: Conflict-of-interest statement: None of the authors have any conflict of interest declare that is applicable to the present manuscript.

The aim was to determine the factors associated with the use of delayed abdominal closure in pediatric liver transplantation (LT) and whether this affected outcome. From a prospectively maintained database, transplants performed in children (≤18 years) were identified (October 2010 to March 2015). Primary abdominal closure was defined as mass closure performed at time of transplant. Delayed abdominal closure was defined as mass closure not initially performed at the same time as transplant; 230 children underwent LT. Of these, 176 (76.5%) had primary closure. Age was similar between the primary and delayed groups (5.0 ± 4.9 versus 3.9 ± 5.0 years; P = 0.13). There was no difference in the graft-to-recipient weight ratio (GRWR) in the primary and delayed groups (3.4 ± 2.8 versus 4.1 ± 2.1; P = 0.12). Children with acute liver failure (ALF) were more likely to experience delayed closure then those with chronic liver disease (CLD; P < 0.001). GRWR was similar between the ALF and CLD (3.4 ± 2.4 versus 3.6 ± 2.7; P = 0.68). Primary closure children had a shorter hospital stay (P < 0.001), spent fewer days in pediatric intensive care unit (PICU; P = 0.001), and required a shorter duration of ventilation (P < 0.001). Vascular complications (arterial and venous) were similar (primary 8.2% versus delayed 5.6%; P = 0.52). Graft (P = 0.42) and child survival (P = 0.65) in the primary and delayed groups were similar. Considering timing of mass closure after transplant, patients in the early delayed closure group (<6 weeks) were found to experience a shorter time of ventilation (P = 0.03) and in PICU (P = 0.003). In conclusion, ALF was the main determinant of delayed abdominal closure rather than GRWR. The optimal time for delayed closure is within 6 weeks. The use of delayed abdominal closure does not adversely affect graft/child survival. Liver Transplantation 23 352-360 2017 AASLD., (© 2016 by the American Association for the Study of Liver Diseases.)

Liver transplantation remains the treatment of choice for patients with end-stage liver disease. However, allograft availability continues to be a problem, and extending the criteria for organ acceptance is key. Deceased donors after electrical accidents, as well as electricity-traumatized allografts, are not common but should be considered suitable. This study describes 2 cases of heart-beating organ donors with electrical injury to the liver. In 1 case, the electric shock was the cause of death; in the second case, the injury was caused by defibrillation at organ procurement. Both allografts had sustained sizeable electrical injury, and both resulted in excellent early posttransplant outcomes. These cases demonstrate that electrocution is not a contraindication to donation and that electricity-traumatized allografts may remain transplantable after careful assessment. Education of all staff in the management of such donors can optimize utility of such allografts., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Hepatocellular cancer (HCC) is an established indication for liver transplantation. This group is often allocated a donor after cardiac death (DCD) liver as a solution for waiting times. There are concerns that this approach may oncologically disadvantage HCC recipients. The aim of this study was to determine whether DCD transplantation was associated with poorer cancer-related survival in HCC., Methods: Study population was from a single institute (2001-2014) with an HCC listing diagnosis. Variables related to recipient, tumor, and graft were analyzed to determine association with HCC death., Results: There were 347 recipients listed for HCC of which 91 received a DCD. Donor after cardiac death and donor after brain stem death (DBD) had equivalent 1-, 3-, and 5-year overall (P = 0.115) and cancer-specific survival (P = 0.7). On univariate analysis recipient age, sex, model for end stage liver disease, viral etiology had no bearing on the risk of HCC death. Neither did the graft variables of type (DCD vs DBD), donor age, steatosis, cold ischemic time, peak aspartate transaminase, day 5 bilirubin or international normalized ratio after transplant. Only tumor variables of alpha-fetoprotein, number, total diameter, microvascular invasion, and differentiation were predictors of HCC death. On multivariate analysis, predictors of HCC death remained tumor number (P = 0.002), total diameter of tumor(s) (P < 0.001), microvascular invasion (P = 0.025), and poor differentiation (P = 0.021)., Conclusions: Donor liver quality in terms of graft type (DCD) has no influence on cancer related survival in transplant for HCC (hazards ratio, 1.143; 95% confidence interval, 0.528-2.423; P = 0.752).

Primary hyperoxaluria type 1 (PH1) is an inherited metabolic disease that culminates in ESRF. Pre-emptive liver transplantation (pLTx) treats the metabolic defect and avoids the need for kidney transplantation (KTx). An institutional experience of pediatric PH1 LTx is reported and compared to the literature. Between 2004 and 2015, eight children underwent pLTx for PH1. Three underwent pLTx with a median GFR of 40 (30-46) mL/min/1.73 m(2) and five underwent sequential combined liver-kidney transplantation (cLKTx); all were on RRT at the time of cLKTx. In one case of pLTx, KTx was required eight and a half yr later. pLTx was performed in older (median 8 vs. 2 yr) and larger children (median 27 vs. 7.75 kg) that had a milder PH1 phenotype. In pediatric PH1, pLTx, ideally, should be performed before renal and extrarenal systemic oxalosis complications have occurred, and pLTx can be used "early" or "late." Early is when renal function is preserved with the aim to avoid renal replacement. However, in late (GFR < 30 mL/min/1.73 m(2) ), the aim is to stabilize renal function and delay the need for KTx. Ultimately, transplant strategy depends on PH1 phenotype, disease stage, child size, and organ availability., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The introduction of liver transplant listing criteria for hepatocellular cancer (HCC) has significantly improved oncological outcomes and survival. But despite this HCC recurrence is still problematic. There is emerging evidence that the choice of immunosuppression (IS) after transplant for HCC can influence oncological survival and HCC recurrence. The following is a short summary of what has been published on HCC recurrence with the different classes of immunosuppressive agents in present use, concluding with the possible rationalization of the use of these immunosuppressive agents in the post-transplant patient at high risk of recurrence., Competing Interests: The authors have no conflicts of interest to declare.

The following is the first report of a pediatric organ donor with caval agenesis and the subsequent use of this liver for transplantation. Caval embryology and potential implications of utilizing a donor liver with caval agenesis are reviewed., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Early hepatic venous outflow obstruction (HVOO) can be a devastating complication leading to graft loss after liver transplantation (LT). A retrospective study on 777 adult LT recipients over a 5-year period (August 2007 to August 2012) was undertaken to determine the incidence of early HVOO presenting within 3 months of transplant, its clinical features and management, and potential technical risk factors related to the implanting technique. Cases of early HVOO were screened for by identifying recipients with problematic ascites within 3 months of transplant. Definitive diagnosis for HVOO was based on a wedge pressure of >12 mm Hg. Considering only whole livers, the incidence of early problematic ascites was 3% (20/695) of which more than one-third (35%, 7/20) were then confirmed to have HVOO. Overall, the incidence of early HVOO was 1% (7/695). Two hepatic veins (HVs) with extension piggybacks (PBs; n = 423) were the dominant implanting technique in the time period of study rather than the 3 HV PB (n = 182) and caval replacement techniques (n = 82). Considering the implantation technique, all cases of HVOO occurred after 2 HVs when extension PBs had been used with an incidence of 1.7% (7/423). Institutionally, early HVOO was mainly managed surgically by either cavoplasty within a month of transplant (n = 4) or retransplant (n = 1), and the remainder (n = 2) were medically managed with diuretics. In conclusion, early HVOO is rare, and there is no evidence from this study that a given implantation technique is at a higher risk of developing HVOO (2 HV with extension versus 3 HV and caval replacement; P = 0.11). However, early revisional surgery for HVOO can preserve graft function with retransplantation being reserved for when surgical cavoplasty or radiological stenting is technically not possible., (© 2015 American Association for the Study of Liver Diseases.)

Donation after cardiac death (DCD) livers are marginal organs for transplant and their use is associated with a higher risk of primary non function (PNF) or early graft dysfunction (EGD). The aim was to determine if microRNA (miRNA) was able to discriminate between DCD livers of varying clinical outcome. DCD groups were categorized as PNF retransplanted within a week (n=7), good functional outcome (n=7) peak aspartate transaminase (AST) ≤ 1000 IU/L and EGD (n=9) peak AST ≥ 2500 IU/L. miRNA was extracted from archival formalin fixed post-perfusion tru-cut liver biopsies. High throughput expression analysis was performed using miRNA arrays. Bioinformatics for expression data analysis was performed and validated with real time quantitative PCR (RT-qPCR). The function of miRNA of interest was investigated using computational biology prediction algorithms. From the array analysis 16 miRNAs were identified as significantly different (p<0.05). On RT-qPCR miR-155 and miR-940 had the highest expression across all three DCD clinical groups. Only one miRNA, miR-22, was validated with marginal significance, to have differential expression between the three groups (p=0.049). From computational biology miR-22 was predicted to affect signalling pathways that impact protein turnover, metabolism and apoptosis/cell cycle. In conclusion, microRNA expression patterns have a low diagnostic potential clinically in discriminating DCD liver quality and outcome.

Donation after cardiac death (DCD) livers are considered to be marginal organs for solid organ and cell transplantation. Low energy charge (EC) and low purine quantity within the liver parenchyma has been associated with poor outcome after liver transplantation. The aim of this work was to assess the effect of anterograde persufflation (A-PSF) using an electrochemical concentrator on DCD liver energy status and hepatocyte function. Organs utilized for research were DCD livers considered not suitable for transplant. Each liver was formally split, and the control non-persufflated (non-PSF) section was stored in University of Wisconsin (UW) solution at 4°C. The A-PSF liver section was immersed in UW solution on ice, and A-PSF was performed via the portal vein with 40% oxygen. Tissue samples were taken 2 hours after A-PSF from the A-PSF and control non-PSF liver sections for snap freezing. Purine analysis was performed with photodiode array detection. Hepatocytes were isolated from A-PSF and control non-PSF liver sections using a standard organs utilized for research were DCD livers considered not suitable for transplant collagenase perfusion technique. Hepatocyte function was assessed using mitochondrial dehydrogenase activity {3-[4,5-dimethylthiazol-2-y1]-2,5-diphenyl tetrazolium bromide (MTT)} and the sulforhodamine B (SRB) assay for cell attachment. In DCD livers with <30% steatosis (n = 6), A-PSF increased EC from 0.197 ± 0.025 to 0.23 ± 0.035 (P = 0.04). In DCD livers with >30% steatosis (n = 4), A-PSF had no beneficial effect. After isolation (n=4, <30% steatosis), A-PSF was found to increase MTT from 0.92 ± 0.045 to 1.19 ± 0.55 (P < 0.001) and SRB from 2.53 ± 0.12 to 3.2 ± 0.95 (P < 0.001). In conclusion, A-PSF can improve the EC and function of isolated hepatocytes from DCD livers with <30% steatosis., (© 2014 American Association for the Study of Liver Diseases.)

Hepatitis C virus (HCV) is a major health problem that leads to chronic hepatitis, cirrhosis and hepatocellular carcinoma, being the most frequent indication for liver transplantation in several countries. Unfortunately, HCV re-infects the liver graft almost invariably following reperfusion, with an accelerated history of recurrence, leading to 10%-30% of patients progressing to cirrhosis within 5 years of transplantation. In this sense, some groups have even advocated for not re-transplanting this patients, as lower patient and graft outcomes have been reported. However, the management of HCV recurrence is being optimized and several strategies to reduce post-transplant recurrence could improve outcomes, decrease the rate of re-transplantation and optimize the use of available grafts. Three moments may be the focus of potential actions in order to decrease the impact of viral recurrence: the pre-transplant moment, the transplant environment and the post-transplant management. In the pre-transplant setting, it is not well established if reducing the pre transplant viral load affects the risk for HCV progression after transplant. Obviously, antiviral treatment can render the patient HCV RNA negative post transplant but the long-term benefit has not yet been fully established to justify the cost and clinical risk. In the transplant moment, factors as donor age, cold ischemia time, graft steatosis and ischemia/reperfusion injury may lead to a higher and more aggressive viral recurrence. After the transplant, discussion about immunosuppression and the moment to start the treatment (prophylactic, pre-emptive or once-confirmed) together with new antiviral drugs are of interest. This review aims to help clinicians have a global overview of post-transplant HCV recurrence and strategies to reduce its impact on our patients.

The objective of this study was to identify peritransplant predictors of early graft survival and posttransplant parameters that could be used to predict early graft outcomes after pediatric liver transplantation (PLT). The response of children to liver dysfunction after liver transplantation (LT) is poor. No data have been reported for early predictors of poor graft survival, which would potentially be valuable for rescuing children at risk after LT. A retrospective cohort study of 422 PLT procedures performed from 2000 to 2010 at a single center was conducted. Multiple peritransplant variables were analyzed. Univariate and multivariate analyses using receiver operating characteristic curves were performed to identify predictors of early graft loss (ie, at 30, 60, and 90 days). The number needed to treat (NNT) was calculated when the risk factors were identified. Comparisons with the Olthoff criteria for early graft dysfunction in adults were performed. The overall 30-, 60-, and 90-day graft survival rates were 93.6%, 92.6%, and 90.7%, respectively. A recipient age of 0 to 2 or 6 to 16 years, acute liver failure, and a posttransplant day 7 serum bilirubin level > 200 μmol/L were risk factors for graft loss in the 3-strata Cox models. The product of the peak aspartate aminotransferase (AST) level, day 2 international normalized ratio (INR) value, and day 7 bilirubin level [with 30-, 60-, and 90-day areas under the receiver operating characteristic curve (AUROCs) of 0.774, 0.752, and 0.715, respectively] and a day 7 bilirubin level > 200 μmol/L (with 30-, 60-, and 90-day AUROCs of 0.754, 0.661, and 0.635, respectively) provided excellent prediction rates for early graft loss (30-days for Day-7-bilirubin level > 200) in the pediatric population (sensitivity = 72.7%, specificity = 96.6%, positive predictive value = 95.5%, negative predictive value = 78%). The NNT with early retransplantation when the day 7 bilirubin level was >200 μmol/L was 2.17 (unadjusted) or 2.76 (adjusted for graft survival). In conclusion, 2 scores-the product of the peak AST level, day 2 INR value, and day 7 bilirubin level and a posttransplant day 7 bilirubin level > 200 μmol/L-have been identified as clinically valuable tools with high accuracy for predicting early graft loss. A more aggressive attitude to considering early retransplantation in this group may further improve survival after LT., (Copyright © 2012 American Association for the Study of Liver Diseases.)

Liver transplantation is the treatment of choice for selected patients with hepatocellular carcinoma (HCC) on a background of chronic liver disease. Liver resection or locoregional ablative therapies may be indicated for patients with preserved synthetic function without significant portal hypertension. Milan criteria were introduced to select suitable patients for liver transplant with low risk of tumor recurrence and 5-year survival in excess of 70%. Currently the incidence of HCC is climbing rapidly and in a current climate of organ shortage has led to the re-evaluation of locoregional therapies and resectional surgery to manage the case load. The introduction of biological therapies has had a new dimension to care, adding to the complexities of multidisciplinary team working in the management of HCC. The aim of this paper is to give a brief overview of present day management strategies and decision making.

Hepatocellular carcinoma (HCC) is the fifth most common type of cancer in men and the seventh in women and is the third most common cause of death from cancer worldwide [http://globocan.iarc.fr]. The overall incidence of HCC remains high in developing countries and is steadily rising in most industrialized countries [Shariff MI et al., 2009]. A variety of therapeutic modalities is available for treating hepatocellular carcinoma, but orthotopic liver transplantation (OLT) represents a curative option. Due to the shortage of donor organs and the increasing need for liver transplantation in the last decade, local ablation therapy (LAT) has been increasingly used in many centers as a bridge to transplant [Majno PE et al., 1997; Decaens T et al., 2005; Herber S et al., 2005; Bharat A et al., 2006; Obed A et al., 2007; Otto G et al., 2007]. We retrieved from the archive in the Histopathology Laboratory, Institute of Liver Studies, King's College Hospital, London, UK, 28 cases of HCC, which underwent treatment with TACE (Doxorubicin 40 mg/m²) as a bridge to transplantation, between 2008 and 2010. We also analyzed 14 additional post-TACE tumors, classified according to the architectural patterns published by Morisco F et al. (2008), for quantification of necrosis. Extensive tumor necrosis was observed in 12 (42.85%) of the patients. Viable hepatocellular carcinoma showed a wide range of differentiation, from well to poorly differentiated. The phenotype of the tumors was mostly hepatocelluar, but 14% showed a mixed phenotype, including glandular/pseudoglandular formation and cholangiocellular components. The percentage of necrosis ranged between 0% and 100%, with an average of 50.6%. There was no statistical correlation between the total size of the nodules and the surface of necrosis in our series (p=0.125). In conclusion, the systematic pathological assessment of post-TACE resected HCC can help in investigating the biology of treated tumors but needs to incorporate sampling protocols, digital image analysis, phenotypic classification by immunohistochemistry and enzymatic function.

In the last ten years, a multitude of studies focusing on gene expression profiling have attempted to shed light on the molecular and genomic mechanisms leading to hepatocarcinogenesis. One of the downsides of the technology available until recently was that it was limited to RNA extracted from fresh/frozen tissue or cell cultures. Recent advances have made it possible to obtain good quality RNA from formalin-fixed paraffin-embedded (FFPE) tissue, allowing access to a virtually limitless archival resource to be available for retrospective and long-term prospective clinico-pathological studies. Laser-capture microdissection allows the isolation of specific cell populations or of specific microscopic areas of interest from tissue samples. This allows the selective evaluation of gene expression of targeted cell clusters, especially in a very heterogeneous environment as the malignant tissue. In our study, we demonstrated that by laser microdissecting the areas of interest from FFPE tissue we could obtain gene expression signals by running the purified RNA through the Whole Genome DASL assay. A large number of genes were expressed in both subpopulations of hepatocellular carcinoma (classical HCC and cholangiocellular differentiation) as well as in the cirrhotic and non-cirrhotic liver background.

Objective: To assess the incidence and impact of biliary complications in recipients transplanted from donors after cardiac death (DCD) at one single large institution., Background: Shortage of available cadaveric organs is a significant limiting factor in liver transplantation (LT). The use of DCD offers the potential to increase the organ pool. However, early results with DCD liver grafts were associated with a greater incidence of ischemic cholangiopathy (IC), leading to several programs to abandoning this source of organs., Methods: A retrospective analysis of a prospective database from April 2001 to 2010 focused on 167 consecutive DCD-LT. Each DCD transplant was matched with 2 brain death donors (DBD) grafts (n = 333) according to the period of transplantation. Primary outcome measures were biliary complications including the severity of complications, graft survival and patient survival. Minimum follow-up was 3 months., Results: Anastomotic stricture was the most common biliary complication (DCD = 30, 19% vs. DBD = 41, 13%). Most were treated endocoscopically (grade IIIa = 72%), whereas hepatico-jejunostomy (grade IIIb) was performed in 22%. Primary IC occurred in 4 (2.5%) recipients from the DCD group and was absent in the DBD group (P = 0.005). However, none of these patients required retransplantation. Patient and graft survival at 1, 3, and 5 years were similar between DCD and DBD groups (P = 0.106, P = 0.138, P = 0.113, respectively)., Conclusions: The encouraging results with DCD-LT are probably due to the selection of DCD grafts and clear definition of warm ischemia.

De novo cholangiocarcinoma associated with recurrent primary sclerosing cholangitis in the transplanted liver is rare. This case report reviews the literature and highlights the need to consider cholangiocarcinoma in transplanted patients with PSC that clinically/biochemically deteriorate., (© 2011 The Authors. Transplant International © 2011 European Society for Organ Transplantation.)

Background: In the US, the thermal ablation workload for cancer involving the liver is predicted to more than double in the next 5 years, emphasising the need to develop and improve the current technology., Study Design: A multicentre nonrandomised prospective clinical trial (NCT00514930) was undertaken, to assess the efficacy and safety of a new bipolar radiofrequency ablation/aspirator device, in the treatment of primary and secondary cancers of the liver., Results: A total of 34 lesions in 16 patients were ablated at laparotomy and followed up at 4 weeks. The mean diameter of lesion before ablation was 3.2+/-2.22 (range 1-10) cm, the mean volume aspirated during ablation was 9.25+/-7.3 (range 0-25) ml and the mean operative time was 145.95+/-40.7 (range 60-215) min. There was one major complication of a pleural effusion, which required drainage. The mean length of stay was 8+/-3.2 (range 3-14) days. In 11 patients, the ablated tumour was resected. On histological assessment, there was no evidence of viable cancer at the tumour edge. On follow-up computed tomography, the ablation zone fully encompassed the targeted tumour and there were no local complications related to ablation., Conclusion: Initial analysis of the data from this small cohort, with only a short-term follow-up, shows this device to be safe and effective.

Purpose: There are a number of alternative approaches to palliate cancers of the rectosigmoid, which may not be well tolerated or produce effective symptom relief. Therefore, there is a continuing need to develop alternative techniques for palliation. This paper reports our initial assessment of a new bipolar radiofrequency probe (Endoblate)., Methods: Twelve patients with rectosigmoid tumors were treated with Endoblate during transanal endoscopic microsurgery. In ten patients, this was followed by surgical resection and two patients were treated with Endoblate alone. This study was designed to assess the technical utility of the device, immediate complications, and histologic effect., Results: There were no technical problems. In the patients who had resection of the tumor immediately after ablation (n = 10), there were no local complications evident at surgery. Histology of the resected specimens showed that, on average, 82 (range, 60-99) percent of the tumor mass was destroyed in the ablation zone. In the remaining two patients, Endoblate alone was used successfully to stop bleeding from the tumor., Conclusions: These preliminary results illustrate the evolution and endoscopic application of bipolar radiofrequency technology. Endoblate showed potential as a useful and safe tool for the palliation of lower gastrointestinal malignancy.

Objective: To determine whether interventional radiology (IR) or laparotomy (LAP) is the best management of delayed postoperative hemorrhage (DPH) after pancreaticoduodenectomy. Data Source We undertook an electronic search of MEDLINE and selected for analysis only original articles published between January 1, 1990, and December 31, 2007., Study Selection: Two of us independently selected studies reporting on clinical presentation and incidence of postoperative DPH and the following outcomes: complete hemostasis, morbidity, and mortality., Data Extraction: Two of us independently performed data extraction. Data were entered and analyzed by means of dedicated software from The Cochrane Collaboration. A random-effects meta-analytical technique was used for analysis., Data Synthesis: One hundred sixty-three cases of DPH after pancreaticoduodenectomy were identified from the literature. The incidence of DPH after pancreaticoduodenectomy was 3.9%. Seventy-seven patients (47.2%) underwent LAP; 73 (44.8%), IR; and 13 (8%), conservative treatment. On meta-analysis comparing LAP vs IR for DPH, no significant difference was found between the 2 treatment options for complete hemostasis (73% vs 76%; P = .23), mortality (43% vs 20%; P = .14), or morbidity (77% vs 35%; P = .06)., Conclusions: This meta-analysis, although based on data from small case series, is unable to demonstrate any significant difference between LAP and IR in the management of DPH after pancreaticoduodenectomy. The management of this life-threatening complication is difficult, and the appropriate treatment pathway ultimately will be decided by the clinical status of the patient and the institution preference.