Constantino Fondevila

University of Barcelona, Barcino, Catalonia, Spain

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Publications (120)441.37 Total impact

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    ABSTRACT: Introduction: A decade ago we proposed to enlist for transplantation those patients with resected hepatocellular carcinoma (HCC) in whom pathology registered pejorative histological markers (microvascular invasion and/or satellites) (ab initio indication) and not wait for the appearance of recurrence. This study evaluates the outcome of this approach. Methods: From 1995 to 2012, 164 patients with HCC underwent resection. Eighty-five patients were potential candidates to liver transplantation (LT) and were considered for it upon detection of pejorative histological markers. Patients without these markers were followed and salvage LT was considered upon development of tumor recurrence/liver function impairment. Results: Thirty-seven patients were at high-risk and 48 at low-risk of recurrence at pathology. Twenty-three out of 37 high-risk patients recurred during follow-up, but in 9 of them the tumor burden extent contraindicated LT. Seventeen were finally transplanted: 10 of them presented recurrence at imaging/explant. After a median post-transplant follow-up of 50.9 months, HCC had recurred in 2 patients and 5 patients had died, the 5-year survival being 82.4%. Twenty-six of the 48 low-risk patients developed recurrence and 11 of them were transplanted. After a median post-transplant follow-up of 59 months, two patients developed recurrence and 5 died, their 5-year survival being 81.8%. Conclusions: Enlistment of patients at high-risk of recurrence after resection before recurrence development seems a valid strategy and is associated with excellent long-term outcome. Since early (<6 months) recurrence reflects an aggressive tumor behavior leading to tumor extent exceeding transplant criteria, we propose to wait at least 6 months before enlistment. However, once included in the waiting list, priority strategies should be implemented in order to reach effective transplantation prior to the appearance of recurrence. This article is protected by copyright. All rights reserved.
    Hepatology 11/2015; DOI:10.1002/hep.28339 · 11.06 Impact Factor

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    ABSTRACT: Hiliar cholangiocarcinoma is the most common type of cholangiocarcinoma, an represent around 10% of all hepatobiliary tumors. It is an aggressive malignancy, resectable in around 47% of the patients at diagnosis. Complete resection is the most effective and only potentially curative therapy, with a survival rate of less than 12 months in unresectable cases. Axial computerized tomography and magnetic resonance are the most useful image techniques to determine the surgical resectability. Clinically, jaundice and pruritus are the most common symptoms at diagnosis;preoperative biliary drainage is recommended using endoscopic retrograde cholangiography or percutaneous transhepatic cholangiography. Surgery using extended liver resections with an en bloc resection of the liver with vascular reconstruction is the technique with the highest survival. Complete resection with histologically negative resection margins (R0), nodal involvement and metastases are the most important prognostic factors. Copyright © 2015. Publicado por Elsevier España, S.L.U.
    Cirugía Española 08/2015; DOI:10.1016/j.ciresp.2015.07.003 · 0.74 Impact Factor
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    ABSTRACT: IntroductionIn selected patients, radiofrequency ablation (RFA) is a well-established treatment for hepatocellular carcinoma (HCC). However, subcapsular or lesions close to adjacent viscera preclude a percutaneous approach. In this setting laparoscopic-RFA (LRFA) is a potential alternative. The aim of this study was to analyse the safety and feasibility of LRFA in patients with HCC.Patients and Methods Retrospective study of patients with HCC meeting strict inclusion criteria who underwent LRFA at a single Institution from December 2000 to March 2013.ResultsForty-one patients underwent 42 LRFA of 51 nodules. The median size of the nodule was 2.5 (range 1.2–4.7) cm. Thirty-one tumours were subcapsular and 17 located near the gallbladder. Major complications occurred in 17 patients. The initial complete response (ICR) rate was 94% and was lower among tumours located adjacent to the gallbladder. At the end of the follow-up period, the sustained complete response (SCR) rate was 70% and was lower in tumours adjacent to the gallbladder while increased for subcapsular tumours. The 1-, 3- and 5-year overall survival rate was 92.6%, 64.5% and 43%, respectively.ConclusionLRFA of HCC is safe, feasible and achieves excellent results in selected patients. LRFA should be the first-line technique for subcapsular lesions as it minimizes the risk of tumoural seeding and improves ICR. Proximity to gallbladder interferes in treatment efficacy (lower rate of ICR and lower rate of SCR).
    HPB 05/2015; 17(5). DOI:10.1111/hpb.12379 · 2.68 Impact Factor
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    ABSTRACT: It has been suggested that vascular stasis during cardio-circulatory arrest leads to the formation of microvascular thrombi and the viability of organs arising from donation after circulatory determination of death (DCDD) donors may be improved through the application of fibrinolytic therapy. Our aim was to comprehensively study the coagulation profiles of Maastricht category II DCDD donors in order to determine the presence of coagulation abnormalities that could benefit from fibrinolytic therapy. Whole blood from potential DCDD donors suffering out-of-hospital cardiac arrest was sampled after declaration of death in the emergency department, and rotational thromboelastomeric analysis was performed. Between July 2012 and December 2013, samples from 33 potential DCDD donors were analyzed. All patients demonstrated hyperfibrinolysis (HF), as reflected by maximum clot lysis of 98-100% in all cases, indicating that there is no role for additional fibrinolytic therapy in this setting. As well, we observed correlations between thromboelastomeric lysis parameters and maximum hepatic transaminase levels measured in potential donors and renal artery flows measured during ex situ hypothermic oxygenated machine perfusion, indicating that further studies on the utility of thromboelastometry to evaluate organ injury and perhaps even viability in unexpected DCDD may be warranted. © Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.
    American Journal of Transplantation 02/2015; 15(3). DOI:10.1111/ajt.13058 · 5.68 Impact Factor

  • Constantino Fondevila ·

    Liver Transplantation 11/2014; 20(S2). DOI:10.1002/lt.24000 · 4.24 Impact Factor
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    ABSTRACT: To evaluate the results of the treatment with pegylated interferon and ribavirin for recurrence of hepatitis C after liver transplantation in HCV/HIV-coinfected patients.
    Journal of Hepatology 08/2014; DOI:10.1016/j.jhep.2014.07.034 · 11.34 Impact Factor
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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; 14(8). DOI:10.1111/ajt.12758 · 5.68 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; 28(7). DOI:10.1111/ctr.12385 · 1.52 Impact Factor
  • Amelia J. Hessheimer · Claire Billault · Benoit Barrou · Constantino Fondevila ·
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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; 28(6). DOI:10.1111/tri.12344 · 2.60 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; 127(8). DOI:10.1042/CS20140125 · 5.60 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.
    03/2014; 92(3). DOI:10.1016/j.cireng.2013.07.028
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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; 97(1). DOI:10.1097/TP.0b013e3182a8613d · 3.83 Impact Factor

  • Free Radical Biology and Medicine 09/2013; 65:S33. DOI:10.1016/j.freeradbiomed.2013.08.036 · 5.74 Impact Factor

  • Journal of Hepatology 04/2013; 58:S69-S70. DOI:10.1016/S0168-8278(13)60157-9 · 11.34 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. DOI:10.1016/j.ciresp.2012.07.002 · 0.74 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; 37(5). DOI:10.1007/s00268-013-1930-z · 2.64 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 02/2013; 19(2). DOI:10.1002/lt.23558 · 4.24 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; 15(9). DOI:10.1007/s12094-012-0990-0 · 2.08 Impact Factor

Publication Stats

2k Citations
441.37 Total Impact Points


  • 2001-2015
    • University of Barcelona
      • Department of Medicine
      Barcino, Catalonia, Spain
  • 2003-2014
    • Hospital Clínic de Barcelona
      • • Servicio de Cirugía Torácica
      • • Servicio de Cirugía General y Digestiva
      Barcino, Catalonia, Spain
    • Harvard University
      Cambridge, Massachusetts, United States
  • 2004-2013
    • IDIBAPS August Pi i Sunyer Biomedical Research Institute
      Barcino, Catalonia, Spain
  • 2003-2012
    • University of California, Los Angeles
      • • Division of Liver and Pancreas Transplantation
      • • Department of Surgery
      Los Ángeles, California, United States
  • 2011
    • Washington University in St. Louis
      • Department of Surgery
      San Luis, Missouri, United States
  • 2009
    • Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas
      Barcino, Catalonia, Spain
  • 2006
    • CSU Mentor
      Long Beach, California, United States