Constantino Fondevila

University of Barcelona, Barcino, Catalonia, Spain

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Publications (105)292.61 Total impact

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    ABSTRACT: Small-for-size (SFS) injury occurs in partial liver transplantation due to several factors, including excessive portal inflow and insufficient intragraft responses. We aim to determine the role somatostatin plays in reducing portal hyperperfusion and preventing the cascade of deleterious events produced in small grafts. A porcine model of 20% liver transplantation is performed. Perioperatively treated recipients receive somatostatin and untreated controls standard intravenous fluids. Recipients are followed for up to 5 days. In vitro studies are also performed to determine direct protective effects of somatostatin on hepatic stellate cells (HSC) and sinusoidal endothelial cells (SEC). At reperfusion, portal vein flow (PVF) per gram of tissue increased fourfold in untreated animals versus approximately threefold among treated recipients (p = 0.033). Postoperatively, markers of hepatocellular, SEC and HSC injury were improved among treated animals. Hepatic regeneration occurred in a slower but more orderly fashion among treated grafts; functional recovery was also significantly better. In vitro studies revealed that somatostatin directly reduces HSC activation, though no direct effect on SEC was found. In SFS transplantation, somatostatin reduces PVF and protects SEC in the critical postreperfusion period. Somatostatin also exerts a direct cytoprotective effect on HSC, independent of changes in PVF.
    American Journal of Transplantation 06/2014; · 6.19 Impact Factor
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    ABSTRACT: the use of liver retransplantation (ReLT) for Hepatitis C virus (HCV) recurrence is controversial because of subsequent viral recurrence after ReLT. case-control analysis between patients undergoing ReLT for HCV reinfection between 1993 and 2012 (ReLT group: 26 patients) and patients undergoing liver transplantation (LT) for HCV infection immediately before and after each ReLT (LT group: 52 patients). ReLT group had worse hepatocellular function, higher preoperative viral load, higher transfusion requirements and increased number of postoperative complications than LT group. ReLT patients showed a trend towards worse graft survival compared to LT (5 years graft survival: 42.3% vs. 64.3%, p=0.145) but the rate of severe HCV recurrence and infection-free survival were similar. The use of donors older than 60 years led to a lower infection-free survival and graft survival in both groups. Early severe HCV infection rate was similar in both groups but it affected prognosis in ReLT more markedly than in LT (3-year graft survival: 0% vs. 66.7%, p=0.003). ReLT for HCV reinfection has acceptable results when strict selection policies of donor and recipient are applied. However, early severe recurrence more markedly impairs prognosis in ReLT patients than in LT. This article is protected by copyright. All rights reserved.
    Clinical Transplantation 05/2014; · 1.63 Impact Factor
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    ABSTRACT: 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.This article is protected by copyright. All rights reserved.
    Transplant International 05/2014; · 3.16 Impact Factor
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    ABSTRACT: Hepatic microcirculatory dysfunction due to cold storage and warm reperfusion (CS+WR) injury during liver transplantation is partly mediated by oxidative stress and may lead to graft dysfunction. This is especially relevant when steatotic donors are considered. Using primary cultured liver sinusoidal endothelial cells, liver grafts from healthy and steatotic rats, and human liver samples, we aimed at characterizing the effects of a new recombinant form of the human manganese superoxide dismutase (rMnSOD) on hepatic CS+WR injury. After CS+WR, the liver endothelium exhibited accumulation of superoxide and diminished levels of nitric oxide; these detrimental effects were prevented by rMnSOD. CS+WR control and steatotic rat livers exhibited markedly deteriorated microcirculation and acute endothelial dysfunction, together with liver damage, inflammation, oxidative stress, and low nitric oxide. rMnSOD markedly blunted oxidative stress, which was associated with global improvement in liver damage and microcirculatory derangements. rMnSOD addition to cold storage solution maintained its antioxidant capability protecting rat and human liver tissues. In conclusion, rMnSOD represents a new and highly effective therapy to significantly upgrade liver procurement for transplantation.
    Clinical Science 04/2014; · 4.86 Impact Factor
  • Manuel Abradelo, Constantino Fondevila
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    ABSTRACT: El desequilibrio entre el número de candidatos a trasplante hepático y el número de injertos hepáticos disponibles conduce a la mortalidad en lista de espera para trasplante. Dos posibles fuentes de aumentar el número de injertos hepáticos son la bipartición hepática y los donantes en asistolia. Ambas fueron estudiadas en una reunión de consenso de la Sociedad Española de Trasplante Hepático en octubre de 2012. Este artículo recoge las conclusiones de esta reunión.
    Cirugía Española (English Edition). 01/2014;
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    ABSTRACT: Adult living-donor liver transplantation recipients undergo important hemodynamic changes during the procedure, which in turn have proven to be of the upmost importance when dealing with small grafts, to avoid the so-called "small-for-size" syndrome. Back in 2003, we started a hemodynamic monitoring protocol in adult living-donor liver transplantation recipients, which evaluated the hemodynamic status of the patient 24 hr before, during, and 3 days after transplantation. We analyzed the correlation between the same hemodynamic variables measured in the hemodynamic laboratory and those taken in the operating room. With the exception of cardiac index and indexed systemic vascular resistance, all the other hepatic and systemic hemodynamic parameters measured before and during the intervention, as well as during and after the intervention, showed a lack of correlation. The observed lack of correlation may happen due to many factors, such as the influence of vasoactive and anesthetic drugs, total muscular relaxation, or the presence of an open abdomen. As a result, a direct comparison between hemodynamic values should only be done when measured in the same conditions.
    Transplantation 10/2013; · 3.78 Impact Factor
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    ABSTRACT: IntroductionThe recipient of an adult living donor liver transplant (ALDLT) is subjected to great haemodynamic changes that could lead to the appearance of a “small-for-size” syndrome in the post-operative period due to portal hyperflow. The aim of this article is to evaluate these changes, and try to correlate them with portal vein flow during reperfusion.Material and methodsA protocol for monitoring various liver haemodynamic data of the ALDLT recipient before, during and after surgery has been used since the year 2003. The haemodynamic outcome of the recipient after the transplant, as well as the correlation between the portal vein flow during reperfusion and the collected haemodynamic data is analysed.ResultsThere was no small for size syndrome. A significant relationship was found between the portal flow during reperfusion and the portal vein pressure at the beginning of the operation (r=0.46, P<.006) and with the portocaval shunt flow during the anhepatic phase (r=0.55, P<.001). The recipients showed a normal splanchnic hemodynamic state at 3 months after the transplant.Conclusions Haemodynamic monitoring of the ALDLT recipient is essential to prevent portal hyperflow. The relationship between flow during reperfusion and flow through the portocaval shunt means that patients with a higher risk of hyperflow can be identified and can be modified before reperfusion.
    Cirugía Española 03/2013; 91(3):169–176. · 0.87 Impact Factor
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    ABSTRACT: BACKGROUND: Neutrophil gelatinase-associated lipocalin (NGAL) expression is increased in epithelial cancer patients, but studies showing its relation to prognosis are scarce. We aimed to test the ability of preoperative serum NGAL levels (pNGAL) to predict recurrence in metastatic and nonmetastatic colorectal cancer (CRC) patients. METHODS: This retrospective study determined pNGAL levels in 60 healthy individuals, 47 patients with nonmetastatic CRC, and 70 patients with metastatic CRC undergoing curative neoplastic resection. Patients were divided into low- and high-pNGAL groups using a median series-based cutoff. RESULTS: The mean ± SD pNGAL in CRC patients (nonmetastatic and metastatic) was 102.3 ± 66.6 (median 91.4). Nonmetastatic CRC and metastatic CRC patients had higher pNGAL than healthy controls (88 ± 64 and 112 ± 67 vs. 0.6 ± 0.3, respectively, both p < 0.0001). Nonmetastatic CRC patients with deeper tumor invasion and metastatic CRC patients with shorter disease-free interval after CRC resection had higher pNGAL. pNGAL levels correlated with neoplastic tissue volume. CRC patients with recurrence had higher pNGAL than those without recurrence (118 ± 64 vs. 88 ± 66, p = 0.013), and high-pNGAL patients had a higher recurrence rate (59.3 vs. 36.2 %, p = 0.016). Median pNGAL-based risk classification had a sensitivity of 62.5 % for predicting neoplastic progression in CRC patients and 74.3 % for predicting neoplastic progression during the first year after metastatic CRC resection. CONCLUSIONS: pNGAL is higher in CRC patients than in the healthy population, which indicates a potential screening role. High-pNGAL levels are associated with higher neoplastic tissue volume, characteristics of neoplastic invasion, and recurrence, showing a prognostic utility mainly in metastatic CRC patients.
    World Journal of Surgery 02/2013; · 2.23 Impact Factor
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    ABSTRACT: PURPOSE: To analyze the use of proteomic profiles to discriminate healthy from patients with colorectal liver metastases (CLM) and to predict neoplastic recurrence after CLM resection. METHODS: From April 2005 to October 2008, 70 patients operated for first curative resection of CLM and 60 healthy controls underwent determination of preoperative serum proteomic profile. We performed a preliminary training with patients and controls and obtained a classification system based on these patients' proteomic profiles training. The system was then tested about the ability to predict the colon versus rectum origin, metachronous or synchronous appearance, risk of recurrence after CLM resection and whether a sample was from a control or a CLM patient. RESULTS: Sensitivity, specificity, positive and negative predictive values for detecting CLM patients were 75, 100, 100 and 54.6 %, respectively. Best CLM appearance time identification was 50 % and primary tumor origin identification was 62.5 %. Best classifications of neoplastic recurrence within the first year after CLM resection and during the follow-up period were 47.5 and 45 %, respectively. Larger training sets and prevalence-based training sets led to better classification of patients and characteristics. CONCLUSION: Proteomic profiles are a promising tool for discriminating CLM patients from healthy patients and for predicting neoplastic recurrence.
    Clinical and Translational Oncology 01/2013; · 1.28 Impact Factor
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    ABSTRACT: IntroductionLiving donor liver transplantation (LDLT) is an effective treatment for patients with terminal chronic liver disease, despite the high incidence of biliary complications. The objective is to evaluate the results and long-term impact of biliary complications after THDV.Patients and methodsFrom 2000 to 2010, 70 right lobe LDLT were performed. Biliary complications (leakage and stenosis) of the 70 LDLT recipients were collected prospectively and analyzed retrospectively.ResultsA total of 39 patients (55.7%) had some type of biliary complication. Twenty nine presented a leak, and of these, 14 subsequently developed a stricture. In addition, 10 patients had a stenosis without prior leakage. The median time to onset of stenosis was almost a year. Patients with previous biliary leakage were more likely to develop stenosis (58% vs. 29.5% at 5 years, P=.05). With a median follow up of 80 months, 70.8% of patients were successfully treated by interventional radiology. After excluding early mortality, there were no differences in survival according to biliary complications. A decrease of biliary complications was observed in the last 35 patients compared with the first 35.ConclusionsLDLT is associated with a high incidence of biliary complications. However, long-term outcome of patients is not affected. After a median follow-up time of nearly seven years, no differences were found in survival according to the presence of biliary complications.
    Cirugía Española 01/2013; 91(1):17–24. · 0.87 Impact Factor
  • Manuel Abradelo, Constantino Fondevila
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    ABSTRACT: The disbalance between the number of candidates to liver transplant and the number of liver grafts leads to waiting list mortality. Two potential ways of increasing the number of liver grafts are split liver transplantation and the transplantation of grafts from non-heart beating donors. Both of them were discussed in a consensus meeting of the Spanish Society of Liver Transplantation in October 2012. This paper outlines the conclusions of that meeting.
    Cirugía Española 01/2013; · 0.87 Impact Factor
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    ABSTRACT: INTRODUCTION: The recipient of an adult living donor liver transplant (ALDLT) is subjected to great haemodynamic changes that could lead to the appearance of a "small-for-size" syndrome in the post-operative period due to portal hyperflow. The aim of this article is to evaluate these changes, and try to correlate them with portal vein flow during reperfusion. MATERIAL AND METHODS: A protocol for monitoring various liver haemodynamic data of the ALDLT recipient before, during and after surgery has been used since the year 2003. The haemodynamic outcome of the recipient after the transplant, as well as the correlation between the portal vein flow during reperfusion and the collected haemodynamic data is analysed. RESULTS: There was no small for size syndrome. A significant relationship was found between the portal flow during reperfusion and the portal vein pressure at the beginning of the operation (r=0.46, P<.006) and with the portocaval shunt flow during the anhepatic phase (r=0.55, P<.001). The recipients showed a normal splanchnic hemodynamic state at 3 months after the transplant. CONCLUSIONS: Haemodynamic monitoring of the ALDLT recipient is essential to prevent portal hyperflow. The relationship between flow during reperfusion and flow through the portocaval shunt means that patients with a higher risk of hyperflow can be identified and can be modified before reperfusion.
    Cirugía Española 12/2012; · 0.87 Impact Factor
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    ABSTRACT: Adult Living donor liver transplantation (aLDLT) is associated to surgical risk in the donor and the possibility of development of small-for-size syndrome (SFSS) in the recipient, both events being of great importance. An excessively small liver graft entails a relative increase in portal blood flow during reperfusion, a factor that predisposes to increased risk of SFSS in the postoperative period, although other causes, related to recipient, graft or technical factors have also been reported. Hemodynamic monitoring protocol was used in 45 consecutive aLDLT recipients. After analyzing various hemodynamic parameters before reperfusion, a significant correlation between temporary portocaval shunt flow during the anhepatic phase and portal vein flow (PVF) after reperfusion of the graft (R(2) =0.3, p <0.001) was found, as well as a correlation between the native liver portal pressure (PP) and PVF after reperfusion (R(2) =0.21, p=0.007). Identification of patients at risk for excessive portal hyperflow will allow its modulation prior to reperfusion. This could favor the use of smaller grafts and ultimately a reduction in donor complications by allowing more limited hepatectomies to be performed. © 2012 American Association for the Study of Liver Diseases.
    Liver Transplantation 10/2012; · 3.94 Impact Factor
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    ABSTRACT: INTRODUCTION: Living donor liver transplantation (LDLT) is an effective treatment for patients with terminal chronic liver disease, despite the high incidence of biliary complications. The objective is to evaluate the results and long-term impact of biliary complications after THDV. PATIENTS AND METHODS: From 2000 to 2010, 70 right lobe LDLT were performed. Biliary complications (leakage and stenosis) of the 70 LDLT recipients were collected prospectively and analyzed retrospectively. RESULTS: A total of 39 patients (55.7%) had some type of biliary complication. Twenty nine presented a leak, and of these, 14 subsequently developed a stricture. In addition, 10 patients had a stenosis without prior leakage. The median time to onset of stenosis was almost a year. Patients with previous biliary leakage were more likely to develop stenosis (58% vs. 29.5% at 5 years, P=.05). With a median follow up of 80 months, 70.8% of patients were successfully treated by interventional radiology. After excluding early mortality, there were no differences in survival according to biliary complications. A decrease of biliary complications was observed in the last 35 patients compared with the first 35. CONCLUSIONS: LDLT is associated with a high incidence of biliary complications. However, long-term outcome of patients is not affected. After a median follow-up time of nearly seven years, no differences were found in survival according to the presence of biliary complications.
    Cirugía Española 10/2012; · 0.87 Impact Factor
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    ABSTRACT: BACKGROUND: Few studies have studied the effects of graft quality on non-urgent liver retransplantation (ReLT) outcomes. We aimed to analyze graft characteristics and survival in non-urgent ReLT and the effect of using grafts with extended criteria on survival. METHODS: Eighty non-urgent ReLT were performed from June 1988 to June 2010. The whole series was divided by identical time periods to study time-related effects. We assessed graft quality with donor risk index (DRI) and Briceño scores and recipient status with the Model for End-stage Liver Diseases and Rosen scores. Low and high-risk grafts were defined by a DRI cutoff of 1.8. RESULTS: Graft survival was similar in both periods (1-, 5-, and 10-year graft survivals: 73.5, 46.9, and 40.8 versus 71, 47.7, and 47.7%, p = 0.935) although donor quality was worse in the second period (DRI: 1.35 ± 0.32 vs. 1.66 ± 0.34, p < 0.001). In the first period high-risk grafts did worse than low-risk grafts (5-year survival: 0 vs. 54.5%, p = 0.002) while in the second period outcomes were similar (5-year survival: 48.6 vs. 56.7 %, p = 0.660). Donor age was the only independent donor factor for graft survival, with lower survival when using grafts from donors over 60-years-old. CONCLUSIONS: Graft quality in ReLT has worsened with time mainly because of older donors but nowadays the use of high-risk grafts in non-urgent ReLT is not associated with worse graft survival because of better perioperative management. Moreover of being selective on recipient conditions, care should be taken when using grafts from donors over 60-years-old for non-urgent ReLT.
    World Journal of Surgery 09/2012; · 2.23 Impact Factor
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    ABSTRACT: Living donor (LD) transplantation has increased recently, but psychosocial aspects of living donation have not been well characterized, as risk factors for the donors. ELIPSY is a project confunded by EAHC, seeking to develop a common methodology for all EU countries for LD assessment/follow-up in the psychosocial sphere (www.eulivingdonor.eu). To evaluate current psychosocial LD assessment/follow-up practices among European centers for key aspects and differences between kidney and liver programs. Within a timeline of 30 months, this phase of the project sought to identify current LD psychosocial assessment/follow-up practices. The final survey concerned two versions focused on the kidney and on liver transplant program. The survey took place in ELIPSY partner centers under their own responsibility. Each of the centers sent the survey to other ones performing LD in their country. Partners in the EULID project includes ones in the United Kingdom, Poland, and Romania. The results were analyzed separately for each program seeking to compare and define differences among them. The survey took place in 10 European countries including 65 centers with LD programs. Positive answers regarding psychosocial assessment/follow-up practices were obtained for 26 (42%) kidney and nine (38%) liver centers. Some centers perform several psychosocial follow-ups but did not explain their tools, whereas the centers that did explain the tools used the same ones for both programs.
    Transplantation Proceedings 09/2012; 44(7):2246-9. · 0.95 Impact Factor
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    ABSTRACT: Liver ischemia-reperfusion injury (IRI) remains a challenging problem in clinical settings. The expression of fibronectin (FN) by endothelial cells is a prominent feature of the hepatic response to injury. Here we investigate the effects of the connecting segment-1 (CS-1) peptide therapy, which blocks FN-α4β1 integrin leukocyte interactions, in a well-established model of 24-h cold liver IRI. CS-1 peptides significantly inhibited leukocyte recruitment and local release of proinflammatory mediators (COX-2, iNOS and TNF-α), ameliorating liver IRI and improving recipient survival rate. CS1 therapy inhibited the phosphorylation of p38 MAPK, a kinase linked to inflammatory processes. Moreover, in addition to downregulating the expression of matrix metalloproteinase-9 (MMP-9) in hepatic IRI, CS-1 peptide therapy depressed the expression of membrane type 1-matrix metalloproteinase (MT1-MMP/MMP-14) by macrophages, a membrane-tethered MMP important for focal matrix proteolysis. Inhibition of p38 MAPK activity, with its pharmacological antagonist SB203580, downregulated MMP-9 and MT1-MMP/MMP-14 expressions by FN-stimulated macrophages, suggesting that p38 MAPK kinase pathway controls FN-mediated inductions of MMP-9 and MT1-MMP/MMP-14. Hence, this study provides new insights on the role of FN in liver injury, which can potentially be applied to the development of new pharmacological strategies for the successful protection against hepatic IRI.
    American Journal of Transplantation 07/2012; 12(10):2689-99. · 6.19 Impact Factor
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    ABSTRACT: 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. 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. 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. 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.
    Transplantation 06/2012; 94(1):22-9. · 3.78 Impact Factor
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    ABSTRACT: 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. 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. 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.
    Current opinion in organ transplantation 01/2012; 17(2):143-7. · 3.27 Impact Factor
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    ABSTRACT: Maastricht type 2 donation after cardiac death (DCD) donors suffer sudden and unexpected cardiac arrest, typically outside the hospital; they have significant potential to expand the donor pool. Herein, we analyze the results of transplanted livers and all potential donors treated under our type 2 DCD protocol. Cardiac arrest was witnessed; potential donors arrived at the hospital after attempts at resuscitation had failed. Death was declared based on the absence of cardiorespiratory activity during a 5-min no-touch period. Femoral vessels were cannulated to establish normothermic extracorporeal membrane oxygenation, which was maintained until organ recovery. From April 2002 to December 2010, there were 400 potential donors; 34 liver transplants were performed (9%). Among recipients, median age, model for end-stage liver disease and cold and reperfusion warm ischemic times were 55 years (49-60), 19 (14-21) and 380 (325-430) and 30 min (26-35), respectively. Overall, 236 (59%) and 130 (32%) livers were turned down due to absolute and relative contraindications to donate, respectively. One-year recipient and graft survivals were 82% and 70%, respectively (median follow-up 24 months). The applicability of type 2 DCD liver transplant was <10%; however, with better preservation technology and expanded transplant criteria, we may be able to improve this figure significantly.
    American Journal of Transplantation 11/2011; 12(1):162-70. · 6.19 Impact Factor

Publication Stats

1k Citations
292.61 Total Impact Points

Institutions

  • 2001–2014
    • University of Barcelona
      • Department of Medicine
      Barcino, Catalonia, Spain
  • 1998–2014
    • Hospital Clínic de Barcelona
      • • Servicio de Cirugía Torácica
      • • Servicio de Cirugía General y Digestiva
      Barcino, Catalonia, Spain
  • 2011
    • National and Kapodistrian University of Athens
      • Division of Surgery V
      Athens, Attiki, Greece
  • 2010
    • Southern Medical Clinic
      San Fernando, City of San Fernando, Trinidad and Tobago
  • 2004–2010
    • IDIBAPS August Pi i Sunyer Biomedical Research Institute
      Barcino, Catalonia, Spain
    • University of California, Los Angeles
      • Division of Liver and Pancreas Transplantation
      Los Angeles, CA, United States
  • 2006
    • CSU Mentor
      Long Beach, California, United States
    • University of Southern California
      • Department of Surgery
      Los Angeles, CA, United States