Publications by authors named "Amelia J Hessheimer"

37 Publications

A systematic review and meta-analyses of regional perfusion in donation after circulatory death solid organ transplantation.

Transpl Int 2021 Nov 19;34(11):2046-2060. Epub 2021 Oct 19.

Transplantation Research Group, Department of Microbiology, Immunology, and Transplantation, KU Leuven, Leuven, Belgium.

In donation after circulatory death (DCD), (thoraco)abdominal regional perfusion (RP) restores circulation to a region of the body following death declaration. We systematically reviewed outcomes of solid organ transplantation after RP by searching PubMed, Embase, and Cochrane libraries. Eighty-eight articles reporting on outcomes of liver, kidney, pancreas, heart, and lung transplants or donor/organ utilization were identified. Meta-analyses were conducted when possible. Methodological quality was assessed using National Institutes of Health (NIH)-scoring tools. Case reports (13/88), case series (44/88), retrospective cohort studies (35/88), retrospective matched cohort studies (5/88), and case-control studies (2/88) were identified, with overall fair quality. As blood viscosity and rheology change below 20 °C, studies were grouped as hypothermic (HRP, ≤20 °C) or normothermic (NRP, >20 °C) regional perfusion. Data demonstrate that RP is a safe alternative to in situ cold preservation (ISP) in uncontrolled and controlled DCDs. The scarce HRP data are from before 2005. NRP appears to reduce post-transplant complications, especially biliary complications in controlled DCD livers, compared with ISP. Comparisons for kidney and pancreas with ISP are needed but there is no evidence that NRP is detrimental. Additional data on NRP in thoracic organs are needed. Whether RP increases donor or organ utilization needs further research.
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http://dx.doi.org/10.1111/tri.14121DOI Listing
November 2021

Somatostatin Therapy Improves Stellate Cell Activation and Early Fibrogenesis in a Preclinical Model of Extended Major Hepatectomy.

Cancers (Basel) 2021 Aug 7;13(16). Epub 2021 Aug 7.

General & Digestive Surgery Service, Hospital Clínic, 08036 Barcelona, Spain.

Liver resection treats primary and secondary liver tumors, though clinical applicability is limited by the remnant liver mass and quality. Herein, major hepatic resections were performed in pigs to define changes associated with sufficient and insufficient remnants and improve liver-specific outcomes with somatostatin therapy. Three experimental groups were performed: 75% hepatectomy (75H), 90% hepatectomy (90H), and 90% hepatectomy + somatostatin (90H + SST). Animals were followed for 24 h (N = 6) and 5 d (N = 6). After hepatectomy, portal pressure gradient was higher in 90H versus 75H and 90H + SST (8 (3-13) mmHg vs. 4 (2-6) mmHg and 4 (2-6) mmHg, respectively, < 0.001). After 24 h, changes were observed in 90H associated with stellate cell activation and collapse of sinusoidal lumen. Collagen chain type 1 alpha 1 mRNA expression was higher, extracellular matrix width less, and percentage of collagen-staining areas greater at 24 h in 90H versus 75H and 90H + SST. After 5 d, remnant liver mass was higher in 75H and 90H + SST versus 90H, and Ki-67 immunostaining was higher in 90H + SST versus 75H and 90H. As well, more TUNEL-staining cells were observed in 90H versus 75H and 90H + SST at 5 d. Perioperative somatostatin modified portal pressure, injury, apoptosis, and stellate cell activation, stemming changes related to hepatic fibrogenesis seen in liver remnants not receiving treatment.
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http://dx.doi.org/10.3390/cancers13163989DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8392429PMC
August 2021

Consensus statement on normothermic regional perfusion in donation after circulatory death: Report from the European Society for Organ Transplantation's Transplant Learning Journey.

Transpl Int 2021 Nov;34(11):2019-2030

Department of Surgery, Addenbrooke's Hospital, Cambridge, UK.

Normothermic regional perfusion (NRP) in donation after circulatory death (DCD) is a safe alternative to in situ cooling and rapid procurement. An increasing number of countries and centres are performing NRP, a technically and logistically challenging procedure. This consensus document provides evidence-based recommendations on the use of NRP in uncontrolled and controlled DCDs. It also offers minimal ethical, logistical and technical requirements that form the foundation of a safe and effective NRP programme. The present article is based on evidence and opinions formulated by a panel of European experts of Workstream 04 of the Transplantation Learning Journey project, which is part of the European Society for Organ Transplantation.
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http://dx.doi.org/10.1111/tri.13951DOI Listing
November 2021

Resource utilization and outcomes in emergency general surgery during the COVID19 pandemic: An observational cost analysis.

PLoS One 2021 18;16(6):e0252919. Epub 2021 Jun 18.

General & Digestive Surgery, Institut de Malaties Digestives i Metabòliques (ICMDM), Hospital Clínic Barcelona, IDIBAPS, CIBERehd, University of Barcelona, Barcelona, Spain.

Background: Over the course of the COVID19 pandemic, global healthcare delivery has declined. Surgery is one of the most resource-intensive area of medicine; loss of surgical care has had untold health and economic consequences. Herein, we evaluate resource utilization, outcomes, and healthcare costs associated with unplanned surgery admissions during the height of the pandemic in 2020 versus the same period in 2019.

Methods: Retrospective analysis on patients ≥18 years admitted from the emergency department to General & Digestive and Gastrointestinal Surgery Services between February and May 2019 and 2020 at our center; clinical outcomes and unadjusted and adjusted per-person healthcare costs were analyzed.

Results: Consults and admissions to surgery declined between February and May 2020 by 37% and 19%, respectively, relative to the same period in 2019, with even greater relative decline during late March and early April. Time between onset of symptoms to diagnosis increased from 2±3 days 2019 to 5±22 days 2020 (P = 0.01). Overall hospital stay was two days less in 2020 (P = 0.19). Complications (Comprehensive Complication Index 10.3±23.7 2019 vs. 13.9±25.5 2020, P = 0.10) and mortality rates (3% vs. 4%, respectively, P = 0.58) did not vary. Mean unadjusted per-person costs for patients in the 2019 and 2020 cohorts were 5,886.72€±12,576.33€ and 5,287.62±7,220.16€, respectively (P = 0.43). Following multivariate analysis, costs remained similar (4,656.89€±390.53€ 2019 vs. 4,938.54±406.55€ 2020, P = 0.28).

Conclusions: Healthcare delivery and spending for unplanned general surgery admissions declined considerably due to COVID19. These results provide a small yet relevant illustration of clinical and economic ramifications of this healthcare crisis.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0252919PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8213049PMC
November 2021

Transcriptomic Profiling of the Liver Sinusoidal Endothelium during Cirrhosis Reveals Stage-Specific Secretory Signature.

Cancers (Basel) 2021 May 29;13(11). Epub 2021 May 29.

Liver Vascular Biology Research Group, Barcelona Hepatic Hemodynamic Unit, IDIBAPS, 08036 Barcelona, Spain.

The poor prognosis of chronic liver disease (CLD) generates the need to investigate the evolving mechanisms of disease progression, thus disclosing therapeutic targets before development of clinical complications. Considering the central role of liver sinusoidal endothelial cells (LSECs) in pre-neoplastic advanced CLD, the present study aimed at investigating the progression of CLD from an endothelial holistic perspective. RNAseq defined the transcriptome of primary LSECs isolated from three pre-clinical models of advanced CLD, during the progression of the disease, and from fresh human cirrhotic tissue. At each stage of the disease, the effects of LSECs secretome on neighboring cells and proteomic analysis of LSECs-derived extracellular vesicles (EVs) were also determined. CLD was associated with deep common modifications in the transcriptome of LSECs in the pre-clinical models. Pathway enrichment analysis showed predominance of genes related with pro-oncogenic, cellular communication processes, and EVs biogenesis during CLD progression. Crosstalk experiments revealed endothelial EVs as potent angiocrine effectors. The proteome of LSECs EVs showed stage-specific signatures, including over-expression of tropomyosin-1. Proof-of-principle experiments treating cirrhotic HSCs with recombinant tropomyosin-1 suggested de-activating effects. Our data provide the basis for discovering novel biomarkers and therapeutic targets for new disease-modifying treatments for patients with advanced CLD.
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http://dx.doi.org/10.3390/cancers13112688DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8198220PMC
May 2021

Creation of the ILTS Consensus Statements on DCD and Liver Perfusion: Defining the Future of Liver Transplantation by Returning to the Past.

Transplantation 2021 04;105(4):695-696

Topic Coordinators, ILTS Special Interest Group on DCD, Liver Preservation & Machine Perfusion.

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http://dx.doi.org/10.1097/TP.0000000000003631DOI Listing
April 2021

Regulations and Procurement Surgery in DCD Liver Transplantation: Expert Consensus Guidance From the International Liver Transplantation Society.

Transplantation 2021 05;105(5):945-951

Edinburgh Transplant Center, Royal Infirmary of Edinburgh, United Kingdom.

Donation after circulatory death (DCD) donors are an increasingly more common source of livers for transplantation in many parts of the world. Events that occur during DCD liver recovery have a significant impact on the success of subsequent transplantation. This working group of the International Liver Transplantation Society evaluated current evidence as well as combined experience and created this guidance on DCD liver procurement. Best practices for the recovery and transplantation of livers arising through DCD after euthanasia and organ procurement with super-rapid cold preservation and recovery as well as postmortem normothermic regional perfusion are described, as are the use of adjuncts during DCD liver procurement.
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http://dx.doi.org/10.1097/TP.0000000000003729DOI Listing
May 2021

The hepatic sinusoid: The "muse" in small-for-size liver transplantation.

Am J Transplant 2021 06 18;21(6):1998-1999. Epub 2021 Feb 18.

General & Digestive Surgery, Hospital Clínic Barcelona, Barcelona, Spain.

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http://dx.doi.org/10.1111/ajt.16507DOI Listing
June 2021

Where have all the appendicitis gone? patterns of urgent surgical admissions during the COVID19 pandemic.

Br J Surg 2020 10 31;107(11):e545-e546. Epub 2020 Aug 31.

Gastrointestinal Surgery, Institut Clínic de Malaties Digestives i Metabòliques, Hospital Clínic, University of Barcelona, Barcelona, Spain.

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http://dx.doi.org/10.1002/bjs.11882DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7929223PMC
October 2020

Laparoscopic versus open hemihepatectomy: comprehensive comparison of complications and costs at 90 days using a propensity method.

Updates Surg 2020 Dec 30;72(4):1041-1051. Epub 2020 Jul 30.

Hepatopancreatobiliary Surgery and Transplantation, General and Digestive Surgery Service, Hospital Clínic, IDIBAPS, CIBERehd, University of Barcelona, Barcelona, Spain.

Laparoscopic hemihepatectomy (LHH) may offer advantages over open hemihepatectomy (OHH) in blood loss, recovery, and hospital stay. The aim of this study is to evaluate our recent experience performing hemihepatectomy and compare complications and costs up to 90 days following laparoscopic versus open procedures. Retrospective evaluation of patients undergoing hemihepatectomy at our center 01/2010-12/2018 was performed. Patient, tumor, and surgical characteristics; 90-day complications; and costs were analyzed. Inverse probability of treatment weighting (IPTW) was used to balance covariates. A total of 141 hemihepatectomies were included: 96 OHH and 45 LHH. While operative times were longer for LHH, blood loss and transfusions were less. At 90 days, there were similar rates of liver-specific and surgical complications but fewer medical complications following LHH. Medical complications that arose with greater frequency following OHH were primarily pulmonary complications and urinary and central venous catheter infections. Complications at 90 days were lower following LHH (Clavien-Dindo grade ≥ III OHH 23%, LHH 11%, p = 0.130; Comprehensive Complication Index OHH 20.0 ± 16.1, LHH 10.9 ± 14.2, p = 0.001). While operating costs were higher, costs for hospital stay and readmissions were lower with LHH. Patients undergoing LHH experience a significant reduction in postoperative medical complications and costs, resulting in 90-day cost equity compared with OHH.
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http://dx.doi.org/10.1007/s13304-020-00854-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7680740PMC
December 2020

Donation after circulatory death liver transplantation: consensus statements from the Spanish Liver Transplantation Society.

Transpl Int 2020 08 15;33(8):902-916. Epub 2020 May 15.

Liver Transplant Unit, CIBERehd, IDIBAPS, Hospital Clínic, University of Barcelona, Barcelona, Spain.

Livers from donation after circulatory death (DCD) donors are an increasingly more common source of organs for transplantation. While there are few high-level studies in the field of DCD liver transplantation, clinical practice has undergone progressive changes during the past decade, in particular due to mounting use of postmortem normothermic regional perfusion (NRP). In Spain, uncontrolled DCD has been performed since the late 1980s/early 1990s, while controlled DCD was implemented nationally in 2012. Since 2012, the rise in DCD liver transplant activity in Spain has been considerable, and the great majority of DCD livers transplanted in Spain today are recovered with NRP. A panel of the Spanish Liver Transplantation Society was convened in 2018 to evaluate current evidence and accumulated experience in DCD liver transplantation, in particular addressing issues related to DCD liver evaluation, acceptance criteria, and recovery as well as recipient selection and postoperative management. This panel has created a series of consensus statements for the standard of practice in Spain and has published these statements with the hope they might help guide other groups interested in implementing new forms of DCD liver transplantation and/or introducing NRP into their clinical practices.
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http://dx.doi.org/10.1111/tri.13619DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7496958PMC
August 2020

Posttransplantation HCC Surveillance: Impact on Outcome or Byproduct of Biology?

Transplantation 2020 10;104(10):1997-1998

General and Digestive Surgery, Hospital Clínic, CIBERehd, IDIBAPS, University of Barcelona, Barcelona, Spain.

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http://dx.doi.org/10.1097/TP.0000000000003140DOI Listing
October 2020

A novel and simple formula to predict liver mass in porcine experimental models.

Sci Rep 2019 08 28;9(1):12459. Epub 2019 Aug 28.

Hepatopancreatobiliary Surgery & Transplantation, General & Digestive Surgery Service, Institut Clínic de Malalties Digestives i Metabòliques (ICMDM), Hospital Clínic, CIBERehd, IDIBAPS, University of Barcelona, Barcelona, Spain.

A primary limitation in hepatic surgery is leaving a remnant liver of adequate size and function. Experimental models have been designed to study processes of liver injury and regeneration in this context, yet a formula to accurately calculate liver mass in an animal model is lacking. This study aims to create a novel and simple formula to estimate the mass of the native liver in a species of pigs commonly used in experimental liver surgery protocols. Using data from 200 male weanling Landrace-Large White hybrid pigs, multiple linear regression analysis is used to generate the formula. Clinical features used as variables for the predictive model are body mass and length. The final formula for pig liver mass is as follows: Liver mass (g) = 26.34232 * Body mass (kg) - 1.270629 * Length (cm) + 163.0076; R = 0.7307. This formula for porcine liver mass is simple to use and may be helpful in studies using animals of similar characteristics to evaluate restoration of liver mass following major hepatectomy.
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http://dx.doi.org/10.1038/s41598-019-48781-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6713746PMC
August 2019

Normothermic perfusion and outcomes after liver transplantation.

Transplant Rev (Orlando) 2019 10 15;33(4):200-208. Epub 2019 Jun 15.

Hepatopancreatobiliary Surgery & Transplantation, General & Digestive Surgery Service, Digestive & Metabolic Disease Institute (ICMDM), Hospital Clínic, CIBERehd, IDIBAPS, University of Barcelona, Spain.

Ischemia has been a persistent and largely unavoidable element in solid organ transplantation, contributing to graft deterioration and adverse post-transplant outcomes. In liver transplantation, where available organs arise with greater frequency from marginal donors (i.e., ones that are older, obese, and/or declared dead following cardiac arrest through the donation after circulatory death process), there is increasing interest using dynamic perfusion strategies to limit, assess, and even reverse the adverse effects of ischemia in these grafts. Normothermic perfusion, in particular, is used to restore the flow of oxygen and other metabolic substrates at physiological temperatures. It may be used in liver transplantation both in situ following cardiac arrest in donation after circulatory death donors or during part or all of the ex situ preservation phase. This review article addresses issues relevant to use of normothermic perfusion strategies in liver transplantation, including technical and logistical aspects associated with establishing and maintaining normothermic perfusion in its different forms and clinical outcomes that have been reported to date.
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http://dx.doi.org/10.1016/j.trre.2019.06.001DOI Listing
October 2019

Somatostatin and the "Small-For-Size" Liver.

Int J Mol Sci 2019 May 22;20(10). Epub 2019 May 22.

Hepatopancreatobiliary Surgery and Transplantation, General & Digestive Surgery, Metabolic & Digestive Diseases Institute (ICMDM), Hospital Clínic, CIBERehd, IDIBAPS, University of Barcelona, 08036 Barcelona, Spain.

"Small-for-size" livers arising in the context of liver resection and transplantation are vulnerable to the effects of increased portal flow in the immediate postoperative period. Increased portal flow is an essential stimulus for liver regeneration. If the rise in flow and stimulus for regeneration are excessive; however, liver failure and patient death may result. Somatostatin is an endogenous peptide hormone that may be administered exogenously to not only reduce portal blood flow but also offer direct protection to different cells in the liver. In this review article, we describe key changes that transpire in the liver following a relative size reduction occurring in the context of resection and transplantation and the largely beneficial effects that peri-operative somatostatin therapy may help achieve in this setting.
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http://dx.doi.org/10.3390/ijms20102512DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6566601PMC
May 2019

Normothermic regional perfusion vs. super-rapid recovery in controlled donation after circulatory death liver transplantation.

J Hepatol 2019 04 22;70(4):658-665. Epub 2018 Dec 22.

Hospital Universitario Infanta Cristina, Badajoz, Spain.

Background & Aims: Although there is increasing interest in its use, definitive evidence demonstrating a benefit for postmortem normothermic regional perfusion (NRP) in controlled donation after circulatory death (cDCD) liver transplantation is lacking. The aim of this study was to compare results of cDCD liver transplants performed with postmortem NRP vs. super-rapid recovery (SRR), the current standard for cDCD.

Methods: This was an observational cohort study including all cDCD liver transplants performed in Spain between June 2012 and December 2016, with follow-up ending in December 2017. Each donor hospital determined whether organ recovery was performed using NRP or SRR. The propensity scores technique based on the inverse probability of treatment weighting (IPTW) was used to balance covariates across study groups; logistic and Cox regression models were used for binary and time-to-event outcomes.

Results: During the study period, there were 95 cDCD liver transplants performed with postmortem NRP and 117 with SRR. The median donor age was 56 years (interquartile range 45-65 years). After IPTW analysis, baseline covariates were balanced, with all absolute standardised differences <0.15. IPTW-adjusted risks were significantly improved among NRP livers for overall biliary complications (odds ratio 0.14; 95% CI 0.06-0.35, p <0.001), ischaemic type biliary lesions (odds ratio 0.11; 95% CI 0.02-0.57; p = 0.008), and graft loss (hazard ratio 0.39; 95% CI 0.20-0.78; p = 0.008).

Conclusions: The use of postmortem NRP in cDCD liver transplantation appears to reduce postoperative biliary complications, ischaemic type biliary lesions and graft loss, and allows for the transplantation of livers even from cDCD donors of advanced age.

Lay Summary: This is a propensity-matched nationwide observational cohort study performed using livers recovered from donors undergoing cardiac arrest provoked by the intentional withdrawal of life support (controlled donation after circulatory death, cDCD). Approximately half of the livers were recovered after a period of postmortem in situ normothermic regional perfusion, which restored warm oxygenated blood to the abdominal organs, whereas the remainder were recovered after rapid preservation with a cold solution. The study results suggest that the use of postmortem normothermic regional perfusion helps reduce rates of post-transplant biliary complications and graft loss and allows for the successful transplantation of livers from older cDCD donors.
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http://dx.doi.org/10.1016/j.jhep.2018.12.013DOI Listing
April 2019

Effects of aging on liver microcirculatory function and sinusoidal phenotype.

Aging Cell 2018 Dec 8;17(6):e12829. Epub 2018 Sep 8.

Liver Vascular Biology Research Group, Barcelona Hepatic Hemodynamic Laboratory, IDIBAPS Biomedical Research Institute, University of Barcelona Medical School, Barcelona, Spain.

The socioeconomic and medical improvements of the last decades have led to a relevant increase in the median age of worldwide population. Although numerous studies described the impact of aging in different organs and the systemic vasculature, relatively little is known about liver function and hepatic microcirculatory status in the elderly. In this study, we aimed at characterizing the phenotype of the aged liver in a rat model of healthy aging, particularly focusing on the microcirculatory function and the molecular status of each hepatic cell type in the sinusoid. Moreover, major findings of the study were validated in young and aged human livers. Our results demonstrate that healthy aging is associated with hepatic and sinusoidal dysfunction, with elevated hepatic vascular resistance and increased portal pressure. Underlying mechanisms of such hemodynamic disturbances included typical molecular changes in the cells of the hepatic sinusoid and deterioration in hepatocyte function. In a specific manner, liver sinusoidal endothelial cells presented a dysfunctional phenotype with diminished vasodilators synthesis, hepatic macrophages exhibited a proinflammatory state, while hepatic stellate cells spontaneously displayed an activated profile. In an important way, major changes in sinusoidal markers were confirmed in livers from aged humans. In conclusion, our study demonstrates for the first time that aging is accompanied by significant liver sinusoidal deregulation suggesting enhanced sinusoidal vulnerability to chronic or acute injuries.
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http://dx.doi.org/10.1111/acel.12829DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6260924PMC
December 2018

Heparin but not tissue plasminogen activator improves outcomes in donation after circulatory death liver transplantation in a porcine model.

Liver Transpl 2018 05 10;24(5):665-676. Epub 2018 Apr 10.

Department of Surgery, Institut de Malalties Digestives I Metabòliques, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Hospital Clínic, University of Barcelona, Barcelona, Spain.

Ischemic-type biliary lesions (ITBLs) arise most frequently after donation after circulatory death (DCD) liver transplantation and result in high morbidity and graft loss. Many DCD grafts are discarded out of fear for this complication. In theory, microvascular thrombi deposited during donor warm ischemia might be implicated in ITBL pathogenesis. Herein, we aim to evaluate the effects of the administration of either heparin or the fibrinolytic drug tissue plasminogen activator (TPA) as means to improve DCD liver graft quality and potentially avoid ITBL. Donor pigs were subjected to 1 hour of cardiac arrest (CA) and divided among 3 groups: no pre-arrest heparinization nor TPA during postmortem regional perfusion; no pre-arrest heparinization but TPA given during regional perfusion; and pre-arrest heparinization but no TPA during regional perfusion. In liver tissue sampled 1 hour after CA, fibrin deposition was not detected, even when heparin was not given prior to arrest. Although it was not useful to prevent microvascular clot formation, pre-arrest heparin did offer cytoprotective effects during CA and beyond, reflected in improved flows during regional perfusion and better biochemical, functional, and histological parameters during posttransplantation follow-up. In conclusion, this study demonstrates the lack of impact of TPA use in porcine DCD liver transplantation and adds to the controversy over whether the use of TPA in human DCD liver transplantation really offers any protective effect. On the other hand, when it is administered prior to CA, heparin does offer anti-inflammatory and other cytoprotective effects that help improve DCD liver graft quality. Liver Transplantation 24 665-676 2018 AASLD.
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http://dx.doi.org/10.1002/lt.25013DOI Listing
May 2018

Liver transplantation for acute liver failure.

Cir Esp 2017 Apr 19;95(4):181-189. Epub 2017 Apr 19.

Liver Transplant Unit, Department of Surgery, Hospital Clínic, CIBERehd, University of Barcelona, Barcelona, España. Electronic address:

Before liver transplantation became widely applicable as a treatment option, the mortality rate for acute liver failure was as high as 85%. Today, acute liver failure is a relatively common transplant indication in some settings, but the results of liver transplantation in this context appear to be worse than those for chronic forms of liver disease. In this review, we discuss the indications and contraindications for urgent liver transplantation. In particular, we consider the roles of auxiliary, ABO-incompatible, and urgent living donor liver transplantation and address the management of a «status 1» patient with total hepatectomy and portocaval shunt for toxic liver syndrome.
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http://dx.doi.org/10.1016/j.ciresp.2017.01.008DOI Listing
April 2017

Liver perfusion devices: how close are we to widespread application?

Curr Opin Organ Transplant 2017 Apr;22(2):105-111

General and Digestive Surgery, Institut de Malalties Digestives i Metabòliques (IMDiM), Hospital Clínic, CIBERehd, IDIBAPS, University of Barcelona, Barcelona, Spain.

Purpose Of Review: Ex-situ liver machine perfusion has been the focus of increasing interest over the past decade as a means to improve the quality of livers for transplantation and the applicability of liver transplantation in general. The present review aims to evaluate the experimental basis for liver machine perfusion and the significance of recent reports on its clinical application.

Recent Findings: Although liver machine perfusion has been studied experimentally over a range of temperatures, clinical liver transplant work that has been performed to date has been done using either hypothermic machine perfusion (0-12 °C), HMP or normothermic machine perfusion (35-38 °C, NMP). Both HMP and NMP have been studied clinically in the context of phase I trials demonstrating the feasibility of their application. It has also been shown through a small number of cases that NMP may serve as a useful means to evaluate initially discarded livers to determine viability for subsequent transplantation.

Summary: Although initial clinical results are promising, higher level evidence is still needed to justify more widespread application of machine perfusion in human liver transplantation.
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http://dx.doi.org/10.1097/MOT.0000000000000384DOI Listing
April 2017

Can we prevent ischemic-type biliary lesions in donation after circulatory determination of death liver transplantation?

Liver Transpl 2016 07;22(7):1025-33

General and Digestive Surgery and, University of Barcelona, Barcelona, Spain.

The pool of livers for transplantation consists of an increasingly greater proportion of marginal grafts, in particular those arising through donation after circulatory determination of death (DCD). However, a primary factor limiting the use of marginal livers, and, thereby, the applicability of liver transplantation in general, is concern over the subsequent development of ischemic-type biliary lesion (ITBL). ITBL is a devastating complication of liver transplantation; in its most severe forms, recipients suffer frequent infectious complications that require repeated invasive biliary procedures and ultimately result in either retransplantation or death. In the present review article, we discuss our current understanding of ITBL pathogenesis as it pertains to DCD, in particular. We discuss the most relevant theories regarding its development and provide a comprehensive overview of the most promising strategies we have available today to prevent the appearance of ITBL, strategies that may, furthermore, allow us to transplant a greater proportion of marginal livers in the future. Liver Transplantation 22 1025-1033 2016 AASLD.
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http://dx.doi.org/10.1002/lt.24460DOI Listing
July 2016

Abdominal regional in-situ perfusion in donation after circulatory determination of death donors.

Curr Opin Organ Transplant 2016 06;21(3):322-8

General and Digestive Surgery, Institut de Malalties Digestives i Metabòliques (IMDiM), Hospital Clínic, CIBERehd, IDIBAPS, University of Barcelona, Spain.

Purpose Of Review: Provide an overview regarding the current state of abdominal regional perfusion (ARP) in donation after circulatory determination of death (DCD) organ transplantation, including the principles behind how ARP functions and the most recent results of its clinical application.

Recent Findings: ARP has been applied clinically in DCD at both hypothermic and normothermic temperatures. The use of hypothermic perfusion has primarily been limited to DCD kidney transplantation, whereas normothermic regional perfusion has been used to improve and assess the quality of DCD kidneys, livers, and even a handful of pancreata for transplantation. Results of recent single-center series reflect acceptable rates of early graft function and survival using grafts that might have otherwise been discarded.

Summary: ARP is an important form of donor maintenance that helps improve DCD organ viability and may help expand the applicability of transplantation using organs arising through this process.
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http://dx.doi.org/10.1097/MOT.0000000000000315DOI Listing
June 2016

Pheochromocytoma as a rare cause of arterial hypertension in a patient with autosomal dominant polycystic kidney disease: A diagnostic and therapeutic dilemma.

Int J Surg Case Rep 2015 28;14:85-8. Epub 2015 Jul 28.

Endocrine Surgery, Department of General and Digestive Surgery, Institut Clínic de Malalties Digestives i Metabòliques (ICMDM) Hospital Clínic, University of Barcelona, Barcelona, Spain.

Introduction: Individuals with autosomal dominant polycystic kidney disease (ADPKD) frequently suffer arterial hypertension even prior to significant loss of renal function, a clinical situation that obscures detection of modifiable secondary causes of hypertension.

Presentation Of Case: A 50-year-old man with ADPKD and polycystic liver and resistant hypertension is diagnosed with a 4-cm right adrenal mass. Cross-sectional MRI is indicative of pheochromocytoma versus adrenocortical carcinoma or metastasis, though there are no typical PCC symptoms and plasma and urine metanephrines are within normal ranges. Since malignancy cannot be excluded, right adrenalectomy is performed. Considering that the enlarged liver poses an obstacle for transperitoneal open and laparoscopic approaches, a retroperitoneoscopic approach is used. Surgical pathology reveals a 4.5-cm pheochromocytoma; the patient no longer requires antihypertensive therapy.

Discussion & Conclusion: Pheochromocytoma is a rare but treatable cause of hypertension in ADPKD; given the anatomical complexities these patients present, careful preoperative planning and surgical technique are essential to a favorable outcome.
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http://dx.doi.org/10.1016/j.ijscr.2015.07.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4573597PMC
September 2015

Hypothermic or normothermic abdominal regional perfusion in high-risk donors with extended warm ischemia times: impact on outcomes?

Transpl Int 2015 Jun 17;28(6):700-7. Epub 2014 Jun 17.

Department of Surgery, Institut de Malalties Digestives I Metabòliques (IMDiM), Hospital Clínic, CIBERehd, IDIBAPS, University of Barcelona, Barcelona, Spain.

Donation after circulatory determination of death (DCD) has the potential to increase the applicability of transplantation as a treatment for end-stage organ disease; its use is limited, however, by the warm ischemic damage suffered by potential grafts. Abdominal regional perfusion (ARP) has been employed in this setting to not only curtail the deleterious effects of cardiac arrest by re-establishing oxygenated flow but also test and even improve the viability of the kidneys and liver prior to transplantation. In the present review article, we discuss experimental and clinical studies that have been published to date on the use of ARP in DCD, differentiating between its application under hypothermic and normothermic conditions. In addition to describing results that have been achieved thus far, we describe the major obstacles limiting the broader implementation of ARP in this context as well as potential means for improving the effectiveness of this modality in the future.
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http://dx.doi.org/10.1111/tri.12344DOI Listing
June 2015

Hypothermic oxygenated machine perfusion in porcine donation after circulatory determination of death liver transplant.

Transplantation 2012 Jul;94(1):22-9

Liver Transplant Unit, Institut de Malaties Digestives, Hospital Clinic, CIBERehd, IDIBAPS, University of Barcelona, C/Villaroel 170, Barcelona, Spain.

Background: Livers from donation after circulatory determination-of-death (DCD) donors suffer ischemic injury during a preextraction period of cardiac arrest and are infrequently used for transplantation; they have the potential, however, to considerably expand the donor pool. We aimed to determine whether hypothermic oxygenated machine perfusion would improve or further deteriorate the quality of these livers using a clinically relevant porcine model.

Methods: Donor livers were subjected to 90 min of cardiac arrest and preserved at 4°C with either static cold storage using University of Wisconsin solution (CS, n=6) or oxygenated machine perfusion using University of Wisconsin machine perfusion solution and 25% physiological perfusion pressures (HMP, n=5). After 4 hr of preservation, livers were transplanted into recipient pigs, which were followed intensively for up to 5 days.

Results: Five-day survival was 0 in CS and 20% in HMP. Immediately after reperfusion, hepatocellular injury and function were improved in HMP versus CS. However, HMP grafts also demonstrated significant endothelial and Kupffer cell injury, and a progressive lesion developed 24 to 48 hr after reperfusion that led to death in all but one of the recipient animals.

Conclusions: Although hypothermic oxygenated machine perfusion performed using subphysiological perfusion pressures seems to offer some advantages over cold storage in the preservation of ischemically damaged livers, it simultaneously conditions endothelial and Kupffer cell injury that may ultimately lead to the failure of these grafts.
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http://dx.doi.org/10.1097/TP.0b013e31825774d7DOI Listing
July 2012

Extracorporeal machine liver perfusion: are we warming up?

Curr Opin Organ Transplant 2012 Apr;17(2):143-7

Hepatobiliary and Liver Transplant Surgery, Liver Transplant Unit, Department of Surgery, Institut de Malaties Digestives, Hospital Clínic, CIBERehd, IDIBAPS, University of Barcelona, Barcelona, Spain.

Purpose Of Review: Recently, considerable focus has been placed on the use of hypothermic perfusion ex vivo in abdominal organ transplant. Herein, we discuss the appropriateness of using this modality to preserve livers, in particular those of suboptimal quality, and whether perfusing at warmer temperatures in this context may, in fact, be better.

Recent Findings: Hypothermic perfusion (0-4°C) appears to improve the hepatocellular energy charge and achieve adequate results in normal livers. However, its use for the preservation of suboptimal grafts may lead to significant endothelial and Kupffer cell injury that is incompatible with survival. Studies on the perfusion of suboptimal livers at higher temperatures, on the contrary, indicate that results improve as temperatures approach 37°C, provided that the oxygen supply during perfusion is adequate.

Summary: Normothermic perfusion provides oxygen and other metabolic substrates under physiological conditions; in liver transplant, it appears to be the best option to improve the viability of suboptimal organs.
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http://dx.doi.org/10.1097/MOT.0b013e328351082aDOI Listing
April 2012

Superior preservation of DCD livers with continuous normothermic perfusion.

Ann Surg 2011 Dec;254(6):1000-7

Departments of Surgery, Institut de Malaties Digestives, Hospital Clínic CIBERehd, IDIBAPS, University of Barcelona, Barcelona, Spain.

Objective: Unexpected donation after cardiac death (DCD) donors suffer cardiac arrest suddenly and are maintained with normothermic extracorporeal membrane oxygenation (NECMO) while consent for donation is obtained. The objective of this study was to determine whether ex vivo normothermic machine perfusion (NMP) improves upon the benefits of NECMO in a large-animal model of unexpected DCD liver transplant.

Methods: Donor pigs underwent 90-minute cardiac arrest and were divided in to 3 groups. In the first, livers were preserved immediately with cold storage (CS, n = 6). In the other 2 groups, donors underwent 60-minute NECMO followed by CS (NECMO+CS, n = 6) or NMP (NECMO+NMP, n = 6). After 4-hour preservation, livers were transplanted into recipient pigs.

Results: Five-day survival was 0 in CS, 83% in NECMO+CS, and 100% in NECMO+NMP. After reperfusion, injury, and inflammatory markers rose significantly among CS grafts, all of which developed primary nonfunction. Sixty minutes of NECMO, however, resulted in only 1 death, whereas NECMO followed by NMP led to no deaths and significant improvements in injury, inflammation, and synthetic function in comparison to NECMO and CS.

Conclusion: Although 60 minutes recuperative NECMO is better than CS alone, NMP improves further on NECMO and may have a role in preserving DCD livers in the clinical setting.
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http://dx.doi.org/10.1097/SLA.0b013e31822b8b2fDOI Listing
December 2011
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