José Antonio Ferrón

Hospital Universitario Virgen de las Nieves, Granata, Andalusia, Spain

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Publications (64)95.97 Total impact

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    ABSTRACT: Background. We describe an observational, retrospective study that included patients who underwent a liver transplantation (LT) for hepatocellular carcinoma (HCC) in our center between 2004 and 2012. Methods. Clinical variables were recorded for donors and recipients as diagnosis and treatment, immunosuppressive therapy, toxicity, graft dysfunction, recurrence, and exitus. Fifty-eight patients were analyzed. The mean age was 57 +/- 8 years. The viral etiology of HCC was 50% (n = 29), alcoholic 26% (n = 15), and others, 24% (n = 14). Regarding initial immunosuppressive strategy (IS), 51 patients (87.9%) were treated with standard regimen with corticosteroids (CS) and tacrolimus (TA), compared with 7 patients with impaired renal function (12.1%) who underwent a delayed therapy with calcineurin inhibitors (CNI) mycophenolate mophetil (MMF) + CS. Concomitant use of anti-CD25 monoclonal antibodies was less than 10%. Regarding maintenance, 43 patients (74.1%) were treated with MMF + CNI versus 15 treated only with TA (25.9%). Results. Recurrence of HCC was approximately 12%: 7 patients (2 hepatic only, 5 also extra-hepatic). Mdtus was established in 19 patients (32.75%); only 3 patients (5.17%) were attributable to HCC. Bivariate studies were conducted according to the initial IS (standard regimen versus delayed therapy) and maintenance therapy (MMF + TA versus TA alone), with no differences in any of them in recurrence, treatment toxicity, graft rejection, and dysfunction. Conclusions. In our experience with the IS, we found no differences in the development of recurrent disease, treatment toxicity, development of graft dysfunction, or rejection. We believe that individualized immunosuppressive therapy in these patients is safe and effective.
    Full-text · Article · Oct 2015 · Transplantation Proceedings
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    ABSTRACT: To evaluate the outcome of patients with hepatocellular-cholangiocarcinoma (HCC-CC) or intrahepatic cholangiocarcinoma (I-CC) on pathological examination after liver transplantation for HCC. Information on the outcome of cirrhotic patients undergoing a transplant for HCC and with a diagnosis of HCC-CC or I-CC by pathological study is limited. Multicenter, retrospective, matched cohort 1:2 study. Study group: 42 patients undergoing a transplant for HCC and with a diagnosis of HCC-CC or I-CC by pathological study; and control group: 84 patients with a diagnosis of HCC. I-CC subgroup: 27 patients compared with 54 controls; HCC-CC subgroup: 15 patients compared with 30 controls. Patients were also divided according to the preoperative tumor size and number: uninodular tumors 2 cm or smaller and multinodular or uninodular tumors 2 cm or larger. Median follow-up: 51 (range, 3-142) months. The 1-, 3-, and 5-year actuarial survival rate differed between the study and control groups (83%, 70%, and 60% vs 99%, 94%, and 89%, respectively; P < 0.001). Differences were found in 1-, 3-, and 5-year actuarial survival rates between the I-CC subgroup and their controls (78%, 66%, and 51% vs 100%, 98%, and 93%; P < 0.001), but no differences were observed between the HCC-CC subgroup and their controls (93%, 78%, and 78% vs 97%, 86%, and 86%; P = 0.9). Patients with uninodular tumors 2 cm or smaller in the study and control groups had similar 1-, 3-, and 5-year survival rate (92%, 83%, 62% vs 100%, 80%, 80%; P = 0.4). In contrast, patients in the study group with multinodular or uninodular tumors larger than 2 cm had worse 1-, 3-, and 5-year survival rates than their controls (80%, 66%, and 61% vs 99%, 96%, and 90%; P < 0.001). Patients with HCC-CC have similar survival to patients undergoing a transplant for HCC. Preoperative diagnosis of HCC-CC should not prompt the exclusion of these patients from transplant option.
    No preview · Article · Jan 2014 · Annals of surgery
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    ABSTRACT: A retrospective cohort multicenter study was conducted to analyze the risk factors for tumor recurrence after liver transplantation (LT) in cirrhotic patients found to have an intrahepatic cholangiocarcinoma (iCCA) on pathology examination. We also aimed to ascertain whether there existed a subgroup of patients with single tumors ≤2 cm ("very early") in which results after LT can be acceptable. Twenty-nine patients comprised the study group, eight of whom had a "very early" iCCA (four of them incidentals). The risk of tumor recurrence was significantly associated with larger tumor size as well as larger tumor volume, microscopic vascular invasion and poor degree of differentiation. None of the patients in the "very early" iCCA subgroup presented tumor recurrence compared to 36.4% of those with single tumors >2 cm or multinodular tumors, p = 0.02. The 1-, 3- and 5-year actuarial survival of those in the "very early" iCCA subgroup was 100%, 73% and 73%, respectively. The present is the first multicenter attempt to ascertain the risk factors for tumor recurrence in cirrhotic patients found to have an iCCA on pathology examination. Cirrhotic patients with iCCA ≤2 cm achieved excellent 5-year survival, and validation of these findings by other groups may change the current exclusion of such patients from transplant programs.
    Full-text · Article · Jan 2014 · American Journal of Transplantation
  • N Zambudio · Y Fundora · K Muffak · T Villegas · A Becerra · D Garrote · J.A. Ferrón
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    ABSTRACT: Given the shortage of donors, it has become increasingly necessary to use alternative sources to meet the growing demand for organs, and evolution in the use of asystolic donors is proving to be an important resource in helping to meet those needs. The goal of this study is to describe the initial results of our experience with Type II asystolic donation. An observational retrospective study was conducted to analyze the variables of four cases in this type of donation. After the analysis we conclude that, despite the limited number of cases in our series, the results are compatible with larger series and permit us to continue to value this method as a resource for broadening the donor pool.
    No preview · Article · Dec 2013 · Transplantation Proceedings
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    C San Miguel · Y Fundora · K Muffak · T Villegas · A Becerra · D Garrote · J.A. Ferrón
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    ABSTRACT: We present our experience with a split liver (SL) program shared with the children's liver transplantation (LT) program from 2 different hospitals in the use of partial grafts from cadaver donors in brain death. We describe an observational, retrospective study, which included patients who underwent a SL transplantation in our center between January 2006 and December 2012. Clinical variables were recorded of both donors and recipients and their data were analyzed using SPSS 19.0 software. Of a total of 204 LT, 4 (2%) patients were treated with a SL. The causes of LT were alcoholic cirrhosis in 2 cases, cryptogenic cirrhosis, and primary biliary cirrhosis (PBC). In all cases there was a temporary portocaval shunt. The confluence of the hepatic veins of the recipient was anastomosed to the donor vena cava and arterial anastomosis was performed. The reconstruction was hepato-choledochal in all cases. There were no cases of postreperfusion syndrome or vascular thrombosis and no retransplantation was necessary. Currently, 3 of the 4 cases are still alive. Death in the other patient was due to mesenteric ischemia. Our center has participated in the development of a protocol that considers the indication of this technique provided expert groups are involved in its development, regardless of hospital level. This will expand the pool of donors and partially solve the current problems with available grafting.
    Full-text · Article · Dec 2013 · Transplantation Proceedings
  • M. Cuadros · C. Cano · R. Conde · C. Olmedo · C. Bueno · A. Blanco · J.A. Ferron · P. Palma

    No preview · Article · Jul 2012 · European Journal of Cancer
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    ABSTRACT: This study assess of hepatopulmonary syndrome (HPS) prevalence and the influence of etiology among cirrhotic patients due to an alcoholic or viral etiology. We examined the records of patients were distributed as Group 1, alcoholic (n = 40) and Group 2, hepatic cirrhosis of viral etiology (n = 35). Hepatic cirrhosis status was estimated by CHILD and MELD scores. Presence of clinical ascites spell out was noted as well as size and diastolic functions of the cardiac chambers using two-dimensional transthoracic echocardiography in M mode and by Doppler. HPS was studied with agitated saline serum and intravenous contrast administration. HPS was considered to be present when serum or contrast passed to the left chamber before the 5th cardiac cycle. There was no significant differences among related to sex, age, cirrhosis status or ascites. HPS frequency was 35% in Group 1 versus 64.7% among Group 2-Patients (P = .01). Taking into account the results, we concluded that HPS frequency was related to cirrhotic etiology. Upon multivariate analysis a patients with cirrhosis from viral etiology showed significantly increased HPS frequency compared with those displaying cirrhosis of an alcoholic etiology.
    Full-text · Article · Jul 2012 · Transplantation Proceedings

  • No preview · Article · Mar 2011 · Journal of Hepatology
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    ABSTRACT: Aim: To investigate the effect of parenteral administration of vitamin C on lymphocyte apoptosis from septic patients after abdominal surgery. Study Design: Twenty septic abdominal surgery patients were studied in a prospective, randomized, double-blinded clinical trial. A group of healthy volunteers (n=10) served as reference for baseline parameter values. The patients were randomly assigned to a vitamin C-treated (n=10) or placebo-treated (n=10) group. For a six-day period from 12 h post-surgery, the vitamin C group received450 mg/day iv of the vitamin in 3 doses and the placebo group an identical administration of 5% dextrose. Peripheral blood samples were obtained daily from 24 h after vitamin C administration until day 6 post-surgery (T1d-T6d). Fas (CD95) expression on CD3-positive peripheral blood T-lymphocytes was determined using direct immunofluorescence technique by flow cytometry. Apoptotic rate in ficoll-hypaque separated lymphocytes was estimated by measuring annexin V/propidium iodide staining in a flow cytometer. Results:Lymphocytes apoptotic ratewas significantly higher in the vitamin C-treated group compared with the placebo group (T2d: p=0.041, T4d: p=0.038, T5d: p=0.05, T6d: p=0.037). Vitamin C group showed higher Fas expression compared with the placebo group, but significance was not reached. Conclusion: Postoperative vitamin C treatment of septic abdominal surgery patients exerts a pro-apoptotic effect on peripheral blood lymphocytes, determined by an increased annexin V-binding capacity.
    No preview · Article · Jan 2011
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    ABSTRACT: We investigated whether intraoperative administration of N-acetylcysteine (NAC) to liver transplant recipients affected pH values. This prospective, randomized, double-blind clinical trial included liver transplant recipients who were randomly assigned to NAC-treated (n=25) or placebo (n=25) groups. The NAC-treated group received 100 mg/kg dissolved in 5% dextrose over 15 minutes during the anhepatic phase, followed by a continuous infusion of 50 mg/kg in 5% dextrose during the next 24 hours. The placebo group received equal amounts of 5% dextrose solution during the same times. Peripheral blood samples were drawn in Ca2+-80 IU-containing syringes after induction of anesthesia (I-1), at 15 minutes into the anhepatic phase (I-2) prior to the administration of NAC or placebo, at 5 minutes before reperfusion (I-3), at 5 minutes after reperfusion (I-4), at 20 minutes after reperfusion (I-5), at 60 minutes after reperfusion (I-6), and at 1 hour after completion of the procedure (I-7). pH levels, which were determined using a radiometer ABL77 (Copenhagen, Denmark), were significantly lower among the NAC than the placebo group at I-4 (P=.027) and I-5 (P=.031). An early decrease in pH values was detected in the NAC-treated group at 5 minutes before reperfusion (I-3; P=.051). We concluded that intraoperative NAC administration during the anhepatic phase of liver transplantation significantly decreased recipient pH values at 5 and 20 minutes after reperfusion, a decrease that was detected at 5 minutes before reperfusion (I-3). The decrease seemed to be associated with NAC metabolism.
    Full-text · Article · Oct 2010 · Transplantation Proceedings
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    ABSTRACT: We investigated whether intraoperative administration of N-acetylcysteine (NAC) in liver transplant recipients ameliorated their inflammatory responses by increasing intraoperative plasma levels of interleukin (IL)-4 and IL-10. This prospective, randomized, double-blind clinical trial included liver transplant recipients randomly assigned to the NAC-treated (n = 25) or the placebo (n = 25) group. The NAC-treated group received 100 mg/kg dissolved in 5% dextrose over 15 minutes during the anhepatic phase, followed by a continuous infusion of 50 mg/kg in 5% dextrose over the next 24 hours, whereas the placebo group received equal amounts of 5% dextrose solution during the same time. Peripheral blood samples were drawn in EDTA-containing tubes after induction of anesthesia (I-1); at 15 minutes into the anhepatic phase (I-2) prior to the administration of NAC or placebo; at 5 minutes before reperfusion (I-3); at 10 minutes after reperfusion (I-4); at 20 minutes after reperfusion (I-5); at 60 minutes after reperfusion (I-6); and at 1 hour after completion of the liver transplantation (I-7). Cytokine levels were determined using a technique which combined enzyme-linked immunosorbent assay (ELISA) and flow cytometry. Plasma IL-4 levels were significantly higher among the NAC-treated group than the placebo group at I-3 (P = .046) and I-4 (P = .041). Plasma IL-10 levels showed significant enhancement in the NAC-treated group at 5 minutes before reperfusion (I-3; P = .007). We concluded that intraoperative NAC administration during the anhepatic phase of liver transplantation significantly increased recipient IL-4 plasma levels before and after reperfusion, and IL-10 plasma values before reperfusion (I-3). These enhancements seemed to be associated with a protective effect against reperfusion injury.
    No preview · Article · Dec 2008 · Transplantation Proceedings
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    ABSTRACT: The main objective of this study was to identify differences in gene expression profile using microarray technology in liver transplant recipients with alcoholic cirrhosis before and after liver transplantation. The study was performed in liver transplant recipients with alcoholic cirrhosis (n = 10) and in healthy volunteers (n = 10), as a reference group. Peripheral blood samples were obtained before (T0) and 7 days after liver transplantation (T7d) using tubes with an RNA stabilizer. RNA was purified and quality tested. From each participant in the study, microarrays were done in duplicate using 10 mug of cRNA. After reverse transcription, complementary RNAs were labeled with Cy5 Streptavidine and used for hybridization of 20,000 human genes CodeLink bioarrays (Applied Microarrays, United States) overnight at 37 degrees C. Arrays were read with a laser scanner and quantified and normalized with CodeLink Software 4.2. Liver transplant recipients showed a gene expression profile before transplantation (T0) of 4310 overexpressed genes compared with healthy volunteers, with 407 of these genes increased more than 2-fold (P < .05). After transplantation (T7d), the same group of patients showed a profile of 1011 overexpressed genes compared with T0, with 109 of these genes increased more than 2-fold (P < .05). We determined gene expression profiles in peripheral blood samples obtained before and after liver transplantation, giving a report of array gene expression profiles of peripheral blood samples from each of these patients. One implication of these results is that gene profiling of peripheral blood samples using microarray technology could be used to dynamically monitor the impact and adequacy of immunosuppression in individual patients.
    No preview · Article · Dec 2008 · Transplantation Proceedings
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    ABSTRACT: The main objective of this study was to identify differences in gene expression profiles by liver transplant recipients with hepatitis C virus (HCV) using microarray technology before versus after liver transplantation. The study was performed in liver transplant recipients with HCV (n = 6) versus a group of healthy volunteers (n = 6). Peripheral blood samples were obtained before (T0) and 7 days after liver transplantation (T7d) using tubes with an RNA stabilizer. The quality of purified RNA was tested (28S/18S ratio >1.5) in a bioanalyzer. Each participant in the study underwent microarrays in duplicate using 10 mug of complementary RNA. After reverse transcription, cRNAs were labeled with Cy5 Streptavidine. Hybridization of 20000 human genes CodeLink bioarrays (Applied Microarrays, United States) was performed overnight at 37 degrees C. Arrays read with a laser scanner were normalized with CodeLink Software 4.2. At T0, liver transplant recipients showed 116 over-expressed genes when compared with healthy volunteers, who had 33 genes increased >2-fold (P < .05). At T7d after transplantation, the same group of patients showed 613 over-expressed genes compared with T0, of which 97 genes were increased >2-fold (P < .05). We determined gene expression profiles in peripheral blood samples obtained before and after liver transplantation, reporting the array of gene expression profiles in peripheral blood samples from each of these patients classes. One implication of these results is that gene profiling of peripheral blood samples could be used to dynamically monitor the impact and adequacy of immunosuppression in individual patients using microarray technology.
    No preview · Article · Nov 2008 · Transplantation Proceedings
  • José Manuel Ramia · Karim Muffak · Jesús Villar · Daniel Garrote · José Antonio Ferrón
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    ABSTRACT: Duodenal cancer has a low prevalence in the general population. Metastases from this neoplasm usually affect the lymph nodes, liver or lung. Bone metastases from duodenal cancer are highly infrequent and xiphoid localization is exceptional. We present the case of a patient who, 5 years after undergoing surgery for duodenal adenocarcinoma, developed xiphoid metastasis. We discuss the utility of positron emission tomography in the diagnosis of this entity and the therapeutic options.
    No preview · Article · Jun 2007 · Cirugía Española
  • José Manuel Ramia · Karim Muffak · Jesús Villar · Daniel Garrote · José Antonio Ferrón

    No preview · Article · May 2007 · Cirugía Española
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    ABSTRACT: Mirizzi syndrome (MS) has a low incidence in patients with gallbladder disease. The coexistence of gallbladder cancer seems to be more frequent in patients with MS than in those with gallstones only. We present two patients with MS type II and gallbladder cancer (stages T4N1M0 and T3NxMx). The etiopathogenic mechanisms, diagnostic methods and therapeutic options are discussed.
    No preview · Article · Mar 2007 · Cirugía Española
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    ABSTRACT: Mirizzi syndrome (MS) has a low incidence in patients with gallbladder disease. The coexistence of gallbladder cancer seems to be more frequent in patients with MS than in those with gallstones only. We present two patients with MS type II and gallbladder cancer (stages T4N1M0 and T3NxMx). The etiopathogenic mechanisms, diagnostic methods and therapeutic options are discussed.
    No preview · Article · Feb 2007 · Cirugía Española

  • No preview · Article · Jan 2007 · Cirugía Española
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    ABSTRACT: Prioritizing the liver transplant waiting list (WL) is subject to great variability. We present the experience of four transplant centers in Andalusia (Southern Spain) with a new consensus model of WL management based on the Model for End-Stage Liver Disease (MELD) score. The initial criteria for local prioritizing were: a) cirrhosis with MELD score > or =24, and b) all hepatocellular carcinoma (HCC) admitted to the WL. Fourteen months later new criteria were established: a) cirrhosis with MELD score > or =18, and b) uninodular HCC between 3-5 cm or multinodular HCC (2-3 nodules <3 cm). Access to regional priority was scheduled after three months for patients with cirrhosis or six months for patients with HCC. We analyzed the WL mortality rate, posttransplant survival rate, and overall survival rate over three 14-month periods: A (before implementation of priority criteria), B (initial criteria), and C (current criteria). Priority was given to 36% of recipients in period B and 47% in period C. The WL mortality rate (including removals from WL) was 12.9%, 12.9%, and 10.7% in periods A, B, and C, respectively. One-year graft survival was 79.7%, 72.6%, and 81.2% in the same periods. The overall one-year survival rate for new cases on the WL was 74.9% in period A, 68.6% in period B, and 82.2% in period C. The allocation system and WL management with the current criteria resulted in lower waiting list mortality without reducing posttransplant survival, leading to better survival for all patients listed.
    Full-text · Article · Jan 2007 · Transplantation

  • No preview · Article · Dec 2006 · Cirugía Española