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Long Term Outcome of the Liver Graft: A Clinician Perspective: Recurrent Disease: The Universal Shifting.

Sun, 08/06/2017 - 12:45
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Long Term Outcome of the Liver Graft: A Clinician Perspective: Recurrent Disease: The Universal Shifting.

Liver Transpl. 2017 Aug 05;:

Authors: Strasser SI

PMID: 28779560 [PubMed - as supplied by publisher]

Liver Transplantation: Rejection and Tolerance.

Sun, 08/06/2017 - 12:45
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Liver Transplantation: Rejection and Tolerance.

Liver Transpl. 2017 Aug 05;:

Authors: Taner T

PMID: 28779559 [PubMed - as supplied by publisher]

Pushing the Donor Limits: deceased donor liver transplantation using organs from octogenarian donors.

Sun, 08/06/2017 - 12:45
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Pushing the Donor Limits: deceased donor liver transplantation using organs from octogenarian donors.

Liver Transpl. 2017 Aug 05;:

Authors: Díaz Jaime F, Berenguer M

PMID: 28779558 [PubMed - as supplied by publisher]

Utilization of Hepatitis C RNA-positive Donor Liver for Transplant to Hepatitis C RNA-Negative Recipient.

Sun, 08/06/2017 - 12:45
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Utilization of Hepatitis C RNA-positive Donor Liver for Transplant to Hepatitis C RNA-Negative Recipient.

Liver Transpl. 2017 Aug 05;:

Authors: Saberi B, Hamilton JP, Durand CM, Li Z, Philosophe B, Cameron AM, Sulkowski MS, Gurakar A

PMID: 28779557 [PubMed - as supplied by publisher]

Extreme large-for-size syndrome after adult liver transplantation. A model for predicting a potentially lethal complication.

Sun, 08/06/2017 - 12:45
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Extreme large-for-size syndrome after adult liver transplantation. A model for predicting a potentially lethal complication.

Liver Transpl. 2017 Aug 05;:

Authors: Allard MA, Lopes F, Frosio F, Golse N, Sa Cunha A, Cherqui D, Castaing D, Adam R, Vibert E

Abstract
INTRODUCTION: There is currently no available tool to predict extreme Large-for-size (LFS), a potentially disastrous complication after adult liver transplantation (LT). We aimed to identify the risk factors for extreme LFS and to build a simple predictive model.
METHODS: A cohort of consecutive patients who underwent LT with full graft in a single institution was studied. The extreme LFS was defined by the impossibility to achieve direct fascial closure, even after delayed management, associated with early allograft dysfunction or non-function. CT scan-based measurements of the recipient were done at the level of xiphoid.
RESULTS: After 424 LT for 394 patients, extreme LFS occurred in 10 (2.4%) cases. The 90-day mortality after extreme LFS was 40% vs. 6.5% in other patients (P=0.003). In the extreme LFS group, the male donor-female recipientcombinationwas more often observed (80.0% vs 17.4%; P<0.001). The graft weight (GW)/right antero-posterior distance (RAP) ratio was predictive of extreme LFS with the highest area under curve (AUC:0.95). The optimal cut-off was 100 (sensitivity: 100%; specificity: 88%). The others ratios based on height, weight, body mass index, body surface area, and standard liver volume exhibited lower predictive performance. The final multivariate model included the male donor-female recipient combination and the GW/RAP. Whenthe GWtoRAP ratio increases from 80, 100,to 120, the probability of extreme LFS was of 2.6%, 9.6% and 29.1% in the male donor-female recipient combination, and <1%, 1.2%, and 4.5%, in other combinations.
CONCLUSION: The GW/RAP ratiopredicts extreme LFS, and may be helpful to avoid futile refusal for morphological reasons or to anticipate situation at risk, especially in female recipient. This article is protected by copyright. All rights reserved.

PMID: 28779555 [PubMed - as supplied by publisher]

Bile duct regeneration and immune response by passenger lymphocytes signals biliary recovery versus complications after liver transplantation.

Sun, 08/06/2017 - 12:45
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Bile duct regeneration and immune response by passenger lymphocytes signals biliary recovery versus complications after liver transplantation.

Liver Transpl. 2017 Aug 05;:

Authors: Junger HH, Schlitt HJ, Geissler EK, Fichtner-Feigl S, Brunner SM

Abstract
BACKGROUND: This study aimed to elucidate the impact of epithelial regenerative responses and immune cell infiltration on biliary complications after liver transplantation.
METHODS: Bile duct damage after cold storage was quantified by a BD damage score and correlated with patient outcome in 41 cases. Bacterial infiltration was determined by fluorescence in situ hybridization. Bile duct samples were analyzed by immunohistochemistry for E-cadherin, cytokeratin, CD56, CD14, CD4, CD8 and double-immunofluorescence for cytokine production and by mRNA microarray.
RESULTS: Increased mRNA levels of adherens-junctions (p<0.01) were detected in damaged bile ducts from patients without complications compared to damaged bile ducts from patients with biliary complications. Immunohistochemistry showed increased expression of E-cadherin and cytokeratin in bile ducts without biliary complications (p=0.03; 0.047). Fluorescence in situ hybridization analysis demonstrated translocation of bacteria in bile ducts, however, mRNA analysis suggested an enhanced immune response in bile ducts without biliary complications (p<0.01). Regarding immune cell infiltration, CD4(+) and CD8(+) cells were significantly increased in patients without complications compared to those with complications (p=0.02; 0.009).
CONCLUSIONS: Following bile duct damage during cold storage, we hypothesize that the functional regenerative capacity of biliary epithelium and enhanced local adaptive immune cell infiltration are crucial for bile duct recovery. Such molecular immunological bile duct analyses therefore could help to predict biliary complications in cases of "major" epithelial damage after cold storage. This article is protected by copyright. All rights reserved.

PMID: 28779549 [PubMed - as supplied by publisher]

Trajectory of adherence behavior in pediatric and adolescent liver transplant recipients - the MALT cohort.

Sun, 08/06/2017 - 12:45
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Trajectory of adherence behavior in pediatric and adolescent liver transplant recipients - the MALT cohort.

Liver Transpl. 2017 Aug 05;:

Authors: Shemesh E, Duncan S, Anand R, Shneider BL, Alonso EM, Mazariegos GV, Venick RS, Annunziato RA, Bucuvalas JC

Abstract
Knowledge of the long term trajectory of nonadherence to immunosupressants can inform decisions regarding organ allocation, adherence monitoring, and intervention efforts. The MALT (Medication Adherence in children who had a Liver Transplant) prospective multi-site study followed 400 pediatric and adolescent liver transplant recipients for 2 years, using the Medication Level Variability Index (MLVI) to monitor adherence. We hypothesized that adherence is an unstable (fluctuating) phenomenon: that patients who are adherent in year one may become nonadherent in year 2, and vice-versa. However, we also hypothesized that a majority (more than 50%) of nonadherent patients remain nonadherent over time. We further hypothesized that the longer nonadherence lasts, the higher the likelihood of adverse events (rejection). Finally, we explored the effect of socioeconomic factors on the evolution of adherence over time. Most (59.7%) of MALT patients who were nonadherent in year 1 remained so in year 2; 18.5% of patients who were adherent in year 1 became nonadherent in year 2. Only 4.4% of patients who were adherent in both year 1 and year 2 had a rejection, compared with 22.9% of patients who were nonadherent during one of the years, and 34.9% of those who were nonadherent in both years (p<.001), establishing a "dose dependent" effect of adherence on transplant outcomes. Single-parent households were associated with worsening adherence. Our results suggest that good baseline adherence does not guarantee adherence later on, that nonadherence is likely to persist in the absence of interventions, and that monitoring of adherence and interventions to improve it should be expected to last for years if transplant outcomes are to be improved. This article is protected by copyright. All rights reserved.

PMID: 28779546 [PubMed - as supplied by publisher]

Efficacy of endoscopic self-expandable metal stent placement versus surgical bypass for inoperable pancreatic cancer-related malignant biliary obstruction: a propensity score-matched analysis.

Sun, 08/06/2017 - 12:45
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Efficacy of endoscopic self-expandable metal stent placement versus surgical bypass for inoperable pancreatic cancer-related malignant biliary obstruction: a propensity score-matched analysis.

Surg Endosc. 2017 Aug 04;:

Authors: Ma KW, Chan ACY, She WH, Chok KSH, Dai WC, Tsang S, Cheung TT, Lo CM

Abstract
BACKGROUND AND AIMS: We explored the difference in treatment efficacy of endoscopic self-expendable metal stent (SEMS) and surgical bypass (SB) in the management of malignant biliary obstruction (MBO) secondary to pancreatic cancer.
METHOD: A retrospective analysis was conducted using consecutive patients who were admitted from 2008 to 2016 receiving either endoscopic SEMS or SB. Diagnosis other than pancreatic cancer and SEMS placement as a pre-operative drainage before Whipple's operation was excluded. Propensity score (PS) matching was performed to eliminate the confounding effect of heterogeneity between patients from two treatment groups. The rate of early, late treatment-related events, readmission and re-intervention, the duration of hospitalization, and the cost of treatment were compared.
RESULTS: There were 98 patients undergoing endoscopic SEMS or SB in the study period. The median age was 68.5 years and 52% of the patients had metastatic disease with median survival of 6 months. After 1:1 PS matching, 30 patients from each group were analyzed. The hospital stay was significantly longer in the SB group (13 vs. 5 days, P < 0.001) with a trend of higher rate of early treatment-related events (24.1 vs. 6.7%, P = 0.113). None of the patients in SB group developed recurrent biliary obstruction. Higher readmission rate (36.7 vs. 3.3%, P = 0.004) and re-intervention rate (36.7 vs. 10%, P = 0.033) were found in the SEMS group. The 3-, 6-, and 9-month re-intervention rates for endoscopic SEMS and SB group were 24.9, 29.4, 45.7, and 11.2, 11.2, and 11.2%, respectively (P = 0.03). When all subsequent readmissions were taken into account, there was no significant difference in hospital stay in both groups (7.5 vs. 14 days, P = 0.359); however, the total cost of treatment in SB group was significantly higher than that in the SEMS group (13,307 vs. 7113 USD, P = 0.035).
CONCLUSION: Despite being more invasive and expensive, surgical bypass provides durable relief of biliary obstruction. Endoscopic SEMS is associated with minimal procedural risks and low re-intervention rate, which are important considerations for frail patients with limited life expectancy.

PMID: 28779260 [PubMed - as supplied by publisher]

Genetic association analysis identifies variants associated with disease progression in primary sclerosing cholangitis.

Sun, 08/06/2017 - 12:45
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Genetic association analysis identifies variants associated with disease progression in primary sclerosing cholangitis.

Gut. 2017 Aug 04;:

Authors: Alberts R, de Vries EMG, Goode EC, Jiang X, Sampaziotis F, Rombouts K, Böttcher K, Folseraas T, Weismüller TJ, Mason AL, Wang W, Alexander G, Alvaro D, Bergquist A, Björkström NK, Beuers U, Björnsson E, Boberg KM, Bowlus CL, Bragazzi MC, Carbone M, Chazouillères O, Cheung A, Dalekos G, Eaton J, Eksteen B, Ellinghaus D, Färkkilä M, Festen EAM, Floreani A, Franceschet I, Gotthardt DN, Hirschfield GM, Hoek BV, Holm K, Hohenester S, Hov JR, Imhann F, Invernizzi P, Juran BD, Lenzen H, Lieb W, Liu JZ, Marschall HU, Marzioni M, Melum E, Milkiewicz P, Müller T, Pares A, Rupp C, Rust C, Sandford RN, Schramm C, Schreiber S, Schrumpf E, Silverberg MS, Srivastava B, Sterneck M, Teufel A, Vallier L, Verheij J, Vila AV, Vries B, Zachou K, International PSC Study Group, The UK PSC Consortium, Chapman RW, Manns MP, Pinzani M, Rushbrook SM, Lazaridis KN, Franke A, Anderson CA, Karlsen TH, Ponsioen CY, Weersma RK

Abstract
OBJECTIVE: Primary sclerosing cholangitis (PSC) is a genetically complex, inflammatory bile duct disease of largely unknown aetiology often leading to liver transplantation or death. Little is known about the genetic contribution to the severity and progression of PSC. The aim of this study is to identify genetic variants associated with PSC disease progression and development of complications.
DESIGN: We collected standardised PSC subphenotypes in a large cohort of 3402 patients with PSC. After quality control, we combined 130 422 single nucleotide polymorphisms of all patients-obtained using the Illumina immunochip-with their disease subphenotypes. Using logistic regression and Cox proportional hazards models, we identified genetic variants associated with binary and time-to-event PSC subphenotypes.
RESULTS: We identified genetic variant rs853974 to be associated with liver transplant-free survival (p=6.07×10(-9)). Kaplan-Meier survival analysis showed a 50.9% (95% CI 41.5% to 59.5%) transplant-free survival for homozygous AA allele carriers of rs853974 compared with 72.8% (95% CI 69.6% to 75.7%) for GG carriers at 10 years after PSC diagnosis. For the candidate gene in the region, RSPO3, we demonstrated expression in key liver-resident effector cells, such as human and murine cholangiocytes and human hepatic stellate cells.
CONCLUSION: We present a large international PSC cohort, and report genetic loci associated with PSC disease progression. For liver transplant-free survival, we identified a genome-wide significant signal and demonstrated expression of the candidate gene RSPO3 in key liver-resident effector cells. This warrants further assessments of the role of this potential key PSC modifier gene.

PMID: 28779025 [PubMed - as supplied by publisher]

Pro: Dynamic LVOT Obstruction Should Be Considered an "Expected" Finding in Patients With End-Stage Liver Disease Undergoing Dobutamine Stress Echocardiography in Preparation for Liver Transplantation.

Sun, 08/06/2017 - 12:45
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Pro: Dynamic LVOT Obstruction Should Be Considered an "Expected" Finding in Patients With End-Stage Liver Disease Undergoing Dobutamine Stress Echocardiography in Preparation for Liver Transplantation.

J Cardiothorac Vasc Anesth. 2017 Apr 15;:

Authors: Argalious M, Fares M

PMID: 28778774 [PubMed - as supplied by publisher]

Adipose-derived mesenchymal stem cells promote liver regeneration and suppress rejection in small-for-size liver allograft.

Sun, 08/06/2017 - 12:45
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Adipose-derived mesenchymal stem cells promote liver regeneration and suppress rejection in small-for-size liver allograft.

Transpl Immunol. 2017 Aug 01;:

Authors: Gao W, Zhang L, Zhang Y, Sun C, Chen X, Wang Y

Abstract
Adipose-derived mesenchymal stem cells (ADSCs) possess a liver regeneration capacity and immunosuppressive activity and hold promise in autologous cell-based technology. This study aimed to determine whether autologous ADSCs can improve outcomes in the rat reduced size liver transplantation model. Allogeneic 50% orthotopic liver transplantation followed by administration of autologous ADSCs delivered into the portal vein system was conducted in LEW donor rats and BN recipient rats with phosphate buffered solution (PBS) infusion used as the control. Liver grafts and recipient serum were obtained. We assessed histopathology, regeneration, apoptosis, serum liver enzymes, serum cytokines, and circulating regulatory T cells (Tregs) on postoperative day (POD) 7 and 14. It was found that ADSCs significantly reduced acute rejection and improved the allograft's survival times (median, 24days). Liver function, as assessed by the levels of alanine aminotransferase, aspartate aminotransferase, total bilirubin, as well as liver apoptosis was significantly alleviated in the ADSC group compared with the control group. In addition, ADSC therapy markedly promoted the expression of PCNA in the allograft. Furthermore, levels of interleukin (IL)-10 and transforming growth factor (TGF)-β1 were significantly elevated, whereas those of IL-2 and IL-17 levels were significantly reduced in the ADSC group when compared to the control group. Moreover, flow cytometry analysis revealed that peripheral Tregs had been significantly increased by the infusion of ADSCs. These results demonstrate that implanted autologous ADSCs improve allogeneic reduced size liver allograft outcomes by attenuating acute rejection and reducing inflammatory responses, as well as enhancing liver regeneration.

PMID: 28778713 [PubMed - as supplied by publisher]

Repopulating the Biliary Tree from the Peribiliary Glands.

Sun, 08/06/2017 - 12:45
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Repopulating the Biliary Tree from the Peribiliary Glands.

Biochim Biophys Acta. 2017 Aug 01;:

Authors: de Jong IEM, van Leeuwen OB, Lisman T, Gouw ASH, Porte RJ

Abstract
The larger ducts of the biliary tree contain numerous tubulo-alveolar adnexal glands that are lined with biliary epithelial cells and connected to the bile duct lumen via small glandular canals. Although these peribiliary glands (PBG) were already described in the 19th century, their exact function and role in the pathophysiology and development of cholangiopathies has not become evident until recently. While secretion of serous and mucinous components into the bile was long considered as the main function of PBG, recent studies have identified PBG as an important source for biliary epithelial cell proliferation and renewal. Activation, dilatation, and proliferation of PBG (or the lack thereof) has been associated with various cholagiopathies. Moreover, PBG have been identified as niches of multipotent stem/progenitor cells with endodermal lineage traits. This has sparked research interest in the role of PBG in the pathogenesis of various cholangiopathies as well as bile duct malignancies. Deeper understanding of the regenerative capacity of the PBG may contribute to the development of novel regenerative therapeutics for previously untreatable hepatobiliary diseases. This article is part of a Special Issue entitled: Cholangiocytes in Health and Diseaseedited by Jesus Banales, Marco Marzioni, Nicholas LaRusso and Peter Jansen.

PMID: 28778591 [PubMed - as supplied by publisher]

Direct comparison of UDP-glucuronosyltransferase and cytochrome P450 activities in human liver microsomes, plated and suspended primary human hepatocytes from five liver donors.

Sun, 08/06/2017 - 12:45
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Direct comparison of UDP-glucuronosyltransferase and cytochrome P450 activities in human liver microsomes, plated and suspended primary human hepatocytes from five liver donors.

Eur J Pharm Sci. 2017 Aug 01;:

Authors: den Braver-Sewradj SP, den Braver MW, Baze A, Decorde J, Fonsi M, Bachellier P, Vermeulen NPE, Commandeur JNM, Richert L, Chris Vos J

Abstract
UDP-glucuronosyltransferases (UGTs) and cytochrome P450s (CYPs) are the major enzymes involved in hepatic metabolism of drugs. Hepatic drug metabolism is commonly investigated using human liver microsomes (HLM) or primary human hepatocytes (PHH). We describe the development of a sensitive assay to phenotype activities of six major hepatic UGT isoforms (UGT1A1, UGT1A3, UGT1A4, UGT1A6, UGT1A9 and UGT2B7) in intact PHH by analysis of glucuronidation of selective probe substrates. The non-selective, general substrate 7-hydroxycoumarin was included for comparison. For each liver donor preparation (five donors) UGT activities in cryopreserved suspended and plated PHH were compared to HLM prepared from the same donors. Standard CYP reaction phenotyping of seven major isoforms was performed in parallel. For all donors, CYP- and UGT-isoforms activity profiles were comparable in PHH and HLM, indicating that reaction phenotyping with selective probe substrates in intact cells primarily reflects respective CYP or UGT activity. System-dependent effects on UGT and CYP isoform activity were still found. While UGT activity of UGT1A1 was equivalent in plated and suspended PHH, UGT1A3, UGT1A6 and UGT2B7 activity was higher in suspended PHH and UGT1A9 and UGT1A4 activity was higher in plated PHH. The well-known decrease in activity of most CYP isoforms in plated compared to suspended PHH was confirmed. Importantly, we found a significant loss in CYP2C19 and CYP2B6 in HLM, activity being lower than in intact cells. Taken together, these findings implicate that, dependent on the UGT or CYP isoforms involved in the metabolism of a given compound, the outcome of metabolic assays is strongly dependent on the choice of the in vitro system. The currently described UGT- and CYP- activity profiling method can be used as a standard assay in intact cells and can especially aid in reaction phenotyping of in vitro systems for which a limited number of cells are available.

PMID: 28778465 [PubMed - as supplied by publisher]

Mesenchymal Stem Cells in Fibrotic Disease.

Sat, 08/05/2017 - 12:45
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Mesenchymal Stem Cells in Fibrotic Disease.

Cell Stem Cell. 2017 Aug 03;21(2):166-177

Authors: El Agha E, Kramann R, Schneider RK, Li X, Seeger W, Humphreys BD, Bellusci S

Abstract
Fibrosis is associated with organ failure and high mortality and is commonly characterized by aberrant myofibroblast accumulation. Investigating the cellular origin of myofibroblasts in various diseases is thus a promising strategy for developing targeted anti-fibrotic treatments. Recent studies using genetic lineage tracing technology have implicated diverse organ-resident perivascular mesenchymal stem cell (MSC)-like cells and bone marrow-MSCs in myofibroblast generation during fibrosis development. In this Review, we give an overview of the emerging role of MSCs and MSC-like cells in myofibroblast-mediated fibrotic disease in the kidney, lung, heart, liver, skin, and bone marrow.

PMID: 28777943 [PubMed - in process]

Sarcopenia in hiding: The risk and consequence of underestimating muscle dysfunction in NASH.

Sat, 08/05/2017 - 12:45
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Sarcopenia in hiding: The risk and consequence of underestimating muscle dysfunction in NASH.

Hepatology. 2017 Aug 04;:

Authors: Bhanji RA, Narayanan P, Allen AM, Malhi H, Watt KD

Abstract
Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease worldwide. Up to one third of individuals with NAFLD will develop non-alcoholic steatohepatitis (NASH), which is associated with progression to cirrhosis and is rapidly becoming the leading indication for liver transplantation. Sarcopenia is defined as a progressive and generalized loss of skeletal muscle mass, strength and function. It is seen in up to 60% of patients with end-stage liver disease and portends a poor prognosis. Recent studies have shown sarcopenia is a novel risk factor for developing NAFLD. Pathophysiological mechanisms relating sarcopenia and NASH may include insulin resistance (IR) and increased inflammation. IR leads to accumulation of triglycerides in both muscle tissue and the liver. It also exacerbates proteolysis and leads to muscle depletion. Chronic inflammation leads to liver injury and progression of fibrosis. The inflammatory milieu also stimulates protein catabolism. Viewing skeletal muscle as an endocrine organ that secretes various salutary myokines may help us understand its role in the development of steatosis. A better understanding of the pathophysiology will aid in developing physical and pharmacologic therapeutic interventions. In this review, we will explore the complex inter-relationships between sarcopenia and NASH. We will discuss the impact of sarcopenia in patients with NASH and therapeutic options for the management of sarcopenia. This article is protected by copyright. All rights reserved.

PMID: 28777879 [PubMed - as supplied by publisher]

Discordant rejection in simultaneous pancreas and kidney transplantation: true discordance or analysis artefact ?

Sat, 08/05/2017 - 12:45
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Discordant rejection in simultaneous pancreas and kidney transplantation: true discordance or analysis artefact ?

Transpl Int. 2017 Aug 04;:

Authors: Assalino M, Hadaya K, Andres A, Berney T

Abstract
The article by Parajuli et al published in this issue of Transplant International is the latest, and perhaps the most convincing in a relatively small body of literature, to suggest that in a situation of simultaneous pancreas-kidney transplantation (SPK), in which both organs are from the same donor, one organ may be undergoing acute rejection independently from the other (1). The organ hierarchy in immunogeneicity and susceptibility to rejection is a long known biological phenomenon, with the liver at one end of the spectrum and the intestine the other. It was originally thought that such a hierarchy between kidney and pancreas was in disfavor of the latter (2). This article is protected by copyright. All rights reserved.

PMID: 28777488 [PubMed - as supplied by publisher]

Liver transplantation with geriatric liver allograft in the US: A matter of epidemiology or of outcome requirements?

Sat, 08/05/2017 - 12:45
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Liver transplantation with geriatric liver allograft in the US: A matter of epidemiology or of outcome requirements?

Transpl Int. 2017 Aug 04;:

Authors: Pezzati D, Hassan A, Buccini L, Liu Q, Diago Uso T, Quintini C

Abstract
We read with interest the letter "Liver transplantation with geriatric liver allografts: the current situation in Eurotransplant" by De Boer et al as it analyzes important aspects in the utilization of "older" donor allografts (1). In this communication we would like to discuss how the utilization of elderly donors (≥70 years old) in the United States differs from that of Europe, offer potential explanations for these different utilization pattern and suggest a potential intervention which could function to systematically enhance older liver donor transplantation in the United States. This article is protected by copyright. All rights reserved.

PMID: 28777472 [PubMed - as supplied by publisher]

Pediatric liver transplant patients' transition to adulthood: Patient and parent experiences.

Sat, 08/05/2017 - 12:45
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Pediatric liver transplant patients' transition to adulthood: Patient and parent experiences.

Nurs Health Sci. 2017 Aug 04;:

Authors: Sarigol Ordin Y, Karayurt Ö, Ünek T, Astarcıoğlu İ

Abstract
This qualitative research study describes the experiences of child and adolescent liver transplant recipients and their parents during the patients' transition to adulthood. Data were collected from pediatric liver transplant recipients and their parents during individual interviews, and these were later analyzed using conventional content analysis. Seven main themes emerged: coping, self-management, body image, social relationships, academic life, work life, and live donors. Study results revealed that the patients who received liver transplants during their childhood and adolescence used both effective and ineffective strategies to cope with the difficulties they faced during the transition period into adulthood. The parents experienced many problems: on learning of their child's need for a transplant, parents were advised that they should consider becoming a live donor. This very difficult decision was a source of great stress and required serious consideration. After transplantation the parents wanted their children to have autonomy but could not encourage them because of concerns for their health.

PMID: 28776909 [PubMed - as supplied by publisher]

Emerging role of bevacizumab in management of patients with symptomatic hepatic involvement in Hereditary Hemorrhagic Telangiectasia.

Sat, 08/05/2017 - 12:45
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Emerging role of bevacizumab in management of patients with symptomatic hepatic involvement in Hereditary Hemorrhagic Telangiectasia.

Am J Hematol. 2017 Aug 04;:

Authors: Chavan A, Schumann-Binarsch S, Schmuck B, Oltmer F, Geisthoff U, Hoppe F, Wirsching K, Klempnauer J, Manns M, Thomas RP, Köhne CH

PMID: 28776732 [PubMed - as supplied by publisher]

Sirolimus and Metformin Synergistically Inhibits Colon Cancer In Vitro and In Vivo.

Sat, 08/05/2017 - 12:45
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Sirolimus and Metformin Synergistically Inhibits Colon Cancer In Vitro and In Vivo.

J Korean Med Sci. 2017 Sep;32(9):1385-1395

Authors: Mussin N, Oh SC, Lee KW, Park MY, Seo S, Yi NJ, Kim H, Yoon KC, Ahn SW, Kim HS, Hong SK, Oh DK, Suh KS

Abstract
We estimated the effect of various immunosuppressants (ISs) and metformin (M) to provide theoretical background of optimal therapeutic strategy for de novo colon cancer after liver transplantation (LT). Three colon cancer cell lines (HT29, SW620, and HCT116) were used in in vitro studies. HT29 was also used in BALB/c-nude mice animal models. Following groups were used in both in vitro and in vivo studies: sirolimus (S), tacrolimus (T), cyclosporin A (CsA), M, metformin/sirolimus (Met/S), metformin/tacrolimus (Met/T), and metformin/cyclosporin A (Met/CsA). 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was performed and western blot analyses were performed for mTOR pathway proteins, apoptosis proteins, and epithelial-mesenchymal-transition (EMT) proteins. Tumor volume was measured for 4 weeks after inoculation. MTT-assay revealed significant cell viability inhibition in all 3 colon cancer cell lines in groups of S, M, and Met/S. Of note, group Met/S showed synergistic effect compare to M or S group. Western blot analysis showed significant low levels of all investigated proteins in groups of S and Met/S in both in vitro and in vivo experiment. Tumor growth was significantly inhibited only in the Met/S group. Combination of Met and S showed the most potent inhibition in all colon cancer cell lines. This finding might have application for de novo colon cancer.

PMID: 28776332 [PubMed - in process]

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