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C Fondevila

Publications and source records attributed to C Fondevila.

At least 19 recordsLinked to original sources
PubMed2005

Cost/efficacy clinical trial about the use of T-tube in cadaveric donor liver transplant: preliminary results.

UNLABELLED: Biliary reconstruction is the most common cause of morbidity associated with orthotopic liver transplantation. Our objective was to assess the complications and hospital resources related to the use of a T-tube. MATERIAL AND METHODS: Among 95 liver transplants performed from October 2002 to November 2003, 84 patients were randomized to receive a T-tube or no T-tube. We analyzed all patients with a follow-up of at least of 3 months. RESULTS: Fifty-five transplants were analyzed with 8 months mean follow-up, including twenty eight with T-tube and twenty seven without a T-tube. No patient died during the follow-up. The overall rate of biliary complications was 45.4% (25/55) including 21/28 (75%) in the T-tube group and 4/27(14.8%) in the non-T-tube group (P < .0001). Complications related to T-tube extraction occurred in 48.2% (13/27), including 3 cholangitis and 10 leaks. The costs of hospital resources due to radiological studies were 5329 capital JE, Ukrainian for the T-tube group vs 5785 capital JE, Ukrainian for the non-T-tube group. The costs of hospital resources due to treatment were 28,280 capital JE, Ukrainian for the T-tube group vs 10,088 capital JE, Ukrainian for the non-T-tube group. CONCLUSIONS: Use of a T-tube during orthotopic liver transplantation does not seem justified. Biliary anastomosis stenting is followed by an increased incidence of complications, most of which are related to its use. Hospital stay, radiological studies, and cost of hospital resources are higher among the T-tube patients. Therefore its systematic use is not advisable.

Anastomosis, Surgical↗
PubMed2005

HO-1 upregulation suppresses type 1 IFN pathway in hepatic ischemia/reperfusion injury.

Upregulation of heme oxygenase (HO)-1, a heat shock protein 32, protects against hepatic ischemia/reperfusion (I/R) injury. Activation of "innate" toll-like receptor (TLR) 4 system triggers the I/R injury cascade. This study explores cytoprotective functions of HO-1 overexpression following exogenous administration of cobalt protoporphyrin (CoPP), and its relationship with the TLR4 pathway in a model of mouse partial hepatic warm I/R injury. CoPP treatment markedly improved hepatic function and histology, and suppressed pro-inflammatory cytokine elaboration profile, as compared with untreated controls. Although administration of CoPP did not affect intrahepatic TLR4, it downregulated IFN-inducible protein 10 (IP-10) expression. As IP-10 is the major product of type-1 IFN pathway downstream of TLR4, we then infused recombinant IFN-beta (rIFN-beta) directly into mouse livers. Interestingly, infusion of rIFN-beta upregulated hepatic IP-10 expression. In contrast, adjunctive CoPP treatment decreased IP-10 levels in mouse livers infused with rIFN-beta. Thus, CoPP-induced HO-1 upregulation suppresses type-1 IFN pathway downstream of TLR4 system in hepatic warm I/R injury model.

Animals↗
PubMed2005

Blockade of fibronectin-alpha4beta1 adhesive interactions down-regulates cyclooxygenase-2 inducible nitric oxide synthase and prolongs recipient survival in a 24-hour model of cold hepatic ischemia-reperfusion injury.

We investigated the effects of the connecting segment-1 (CS1) peptide, which blocks fibronectin (FN)-alpha4beta1 integrin interactions, upon recipient survival and extent of tissue injury in a well-established rat liver model of ex vivo 24-hour cold ischemia followed by isotransplantation. In this model, CS1 peptides were administered through the portal vein of rat livers prior to and after cold ischemic storage. In addition, recipients of orthotopic liver transplants (OLT) received a dose of CS1 peptides 1 hour post-OLT. CS1 peptide therapy significantly inhibited the intragraft recruitment of T lymphocytes and neutrophil activation/infiltration, and repressed important mediators of inflammation, such as cyclooxygenase-2, and inducible nitric oxide synthase expression. Importantly, CS1 peptide therapy improved function/histological preservation of liver grafts and extended their 14-day survival from 50% in control to 100% in CS1-treated OLTs. Thus, CS1 peptide-mediated blockade of FN-alpha4beta1 interaction protects against severe ischemia-reperfusion injury experienced otherwise by OLTs. These novel findings document the potential of targeting FN-alpha4beta1 in vivo interaction for improving OLT outcomes.

Animals↗
PubMed2005

Cyclic RGD peptides with high affinity for alpha5beta1 integrin protect genetically fat Zucker rat livers from cold ischemia/reperfusion injury.

We tested a hypothesis that interactions between fibronectin (FN), a key extracellular matrix component, and its integrin alpha5beta1 receptor are important in the development of ischemia/reperfusion (I/R) injury of steatotic liver transplants. We examined the effect of a cyclic RGD peptide (cRGD), with high affinity for alpha5beta1 integrin, in a well-established steatotic rat liver model of ex vivo cold ischemia followed by isotransplantation. In this model, cRGD peptides were administered through the portal vein of steatotic Zucker rat livers prior to and after cold ischemic storage. Lean Zucker recipients of fatty orthotopic liver transplants (OLTs) received an additional course of cRGD peptides 1 hour posttransplantation. cRGD peptide therapy significantly inhibited the recruitment of monocyte/macrophages, and repressed the expression of pro-inflammatory cytokines, such as tumor necrosis factor (TNF)-alpha and interferon (IFN)-gamma. Moreover, it resulted in selective inhibition of inducible nitric oxide synthase (iNOS), and MMP-9 expression. Importantly, cRGD peptide therapy improved the function and histologic preservation of steatotic liver grafts, extending their 14-day survival in lean recipients from 50% in untreated to 100% in cRGD-treated OLTs. Thus, cRGD peptide-mediated blockade of FN-alpha5beta1 interaction protects against severe I/R injury otherwise experienced by steatotic OLTs.

Animals↗
PubMed2005

Portal vein thrombosis in liver transplantation.

In the initial experience of liver transplantation, complete thrombosis and portal vein occlusion were considered to be absolute contraindications for liver transplantation. The incidence of portal thrombosis in patients being prepared for transplantation varies between 5% and 15% according to published series. There are 2 surgical techniques to solve absent or low portal vein flow due to thrombosis. The most widely used technique is thrombectomy and the second technique is insertion of a shunt with a venous graft in the permeable portion of the superior mesenteric vein or in a vein in the splanchnic territory. Portal thrombosis recurrence rates vary among series, ranging from 0% to 25% or even 30%, depending on its extension and severity and also on time the transplantation was performed. Although overall survival is somewhat lower, there are no significant differences in most of the series when patients with portal thrombosis who underwent transplantation are compared with those without.

Humans↗
PubMed2005

One thousand liver transplants: the hospital clinic experience.

OBJECTIVES: Our goal was to study a consecutive series of 1000 liver transplants performed in our institution to evaluate the changes over time in donors, recipients, and results. PATIENTS AND METHODS: With the aim to evaluate differences between transplantation in the first period and the present period, the first consecutive 100 liver transplants performed from June 1988 to June 1990 (first period) were compared with the last consecutive 200 liver transplants performed from January 2001 to June 2003 (second period). RESULTS: Increased donor age, change in donor cerebral death etiology, and increasing numbers of grafts from alternative methods using cadaveric donors were observed in the second period. Piggy-back technique and the biliary anastomosis without a t-tube was also started in the second period. One-year actuarial patient survival was higher in the second period (84% vs 91.3%). The need for retransplantation in the overall series was 95%. One-, 5-, and 10-year actuarial retransplant survival was 67.7%, 51.3%, and 39.4%, respectively. CONCLUSIONS: Technical innovations, better understanding of donor and recipient aspects, and global improvements were the reasons for time-related improved results of liver transplantation.

Adult↗
PubMed2005

Steroids and living liver donation increase tacrolimus blood levels in living donor liver transplantation.

The aim of this study was to determine the tacrolimus blood levels in recipients of living donor liver transplants (LDLT) compared with recipients who undergo whole cadaveric liver grafts and to correlate the tacrolimus trough levels with the 12-hour area under the concentration (AUC) curve. From June 2002 to June 2003, the 10 LDLT were prospectively compared with 11 cadaveric transplants. The main immunosuppression was tacrolimus plus steroids. Intraoperative methylprednisolone was administered to all cadaveric organ recipients and only 6 of the 10 LDLT. Median tacrolimus trough levels at day 10 were 14.1 ng/mL for the LDLT group and 9.1 ng/mL for the CLT group (P = NS). The median tacrolimus AUC at day 10 were 185.2 ngxh/mL and 148.1 ngxh/mL for the LDLT group and the cadaveric group, respectively (P = NS). Median tacrolimus trough levels at day 2 were 24.3 ng/mL versus 9.9 ng/mL in the LDLT recipients with and without steroids, respectively (P < .05). Also, median tacrolimus AUC at day 2 were 239 ngxh/mL and 179.7 ngxh/mL when we compared LDLT recipients with and without steroids (P = NS). A significant correlation was observed between tacrolimus trough levels and AUC in the LDLT group (C.C. = 0.936; P < .0001). In conclusion, LDLT recipients display higher tacrolimus blood levels in comparison with cadaveric liver recipients, with a good correlation between tacrolimus trough levels and AUC. Intraoperative steroid administration induces higher tacrolimus levels in LDLT recipients.

Adrenal Cortex Hormones↗
PubMed2004

p53 and VEGF expression are independent predictors of tumour recurrence and survival following curative resection of gastric cancer.

This study was undertaken to determine the value of tumour microvessel density (MVD) and the expression of p53 and vascular endothelial growth factor (VEGF) as prognostic markers in patients with gastric cancer operated on for cure. In all, 156 patients with curatively resected gastric cancer constituted the basis of this blinded retrospective evaluation. Patients were treated with either surgery alone (n=53) or surgery plus adjuvant chemotherapy (n=103). Tumour MVD, p53 expression, and VEGF expression were assayed using immunohistochemical techniques. After a mean follow-up of 43 months, 64 (41%) patients had died and 55 (35%) patients developed tumour recurrence. Positive correlations between MVD and both p53 (P=0.005) and VEGF (P=0.005) expression were observed. Both MVD >/=100 (P=0.05) and positive VEGF expression (P<0.02) were associated with shorter disease-free survival, and positive VEGF expression (P=0.01) was also associated with shorter overall survival. Multivariate analysis confirmed that, in addition to the pathological tumour stage, lymph node ratio, the extent of lymphadenectomy and perineural invasion, p53 expression, and VEGF expression were independently associated with both disease-free survival (P<0.0005 and 0.02, respectively) and overall survival (P<0.02 and 0.01, respectively). Finally, patients whose tumours did not show p53 expression had a survival benefit compared to those expressing p53 when treated with adjuvant chemotherapy (P=0.01). This investigation demonstrates that p53 expression and VEGF expression are independent prognostic factors for both disease-free survival and overall survival in patients with curatively resected gastric cancer, and that p53 status may also influence response to chemotherapy.

Adult↗
PubMed2004

Infectious enteritis after intestinal transplantation: incidence, timing, and outcome.

AIM: To review the incidence, timing, and outcome of infectious enteritis after intestinal transplantation (IT). METHOD: A retrospective review of all patients undergoing IT at a single institution between 1991 and 2003 was analyze with standard statistical tools. RESULTS: Among 33 IT recipients, 13 (39%) developed 20 culture- or biopsy-proven episodes of infectious enteritis. The recipient demographics were 77% men and median age 2.6 years. Infections were diagnosed at a median of 76 days (32 to 1800) after IT. There were 14 viral (CMV one, rotavirus eight, adenovirus four, EBV one, three bacterial (Clostridium difficile), and three other infections (Giardia lamblia one, cryptosporidium two). Complete resolution was achieved in 17 (94%) infectious after appropriate antimicrobial or conservative therapy. Interestingly, there were six rejection episodes following infectious enteritis. Grafts were lost to rejection after rotaviral enteritis (n = 1) and adenoviral enteritis misdiagnosed as rejection (n = 1). Patient and graft survival were not adversely affected by infections. CONCLUSIONS: Infectious enteritis occurs frequently after IT. Viral agents are the cause in two-thirds of cases. With supportive care and appropriate treatment, resolution is possible in the majority of cases. Differentiating rejection and infection by histopathology can be difficult.

Adult↗
PubMed2004

Improved outcome after intestinal transplantation at a single institution over 12 years.

PURPOSE: To evaluate the outcomes of patients undergoing intestinal transplantation (IT). METHODS: Retrospective review was undertaken using existing medical records and database. RESULTS: Between November 1991 and May 2003, 114 patients were referred for consideration for IT, of which 33 patients received 37 intestinal allografts. All patients had intestinal failure and all patients had significant complications from total parenteral nutrition (TPN). TPN was the predominant cause of liver failure (63%). Combined liver intestinal grafts were used in the majority of patients. Overall 1- and 3-year patient survival is 77% and 52% with patients transplanted since 1999 having a 1- and 3-year survival of 94% and 73%, respectively. The most common cause of death was sepsis. No graft or patient was lost to cytomegalovirus or Epstein-Barr virus disease. Twenty-seven percent of allografts were lost to rejection. Long-term TPN independence is 82% for grafts more than 30 days after IT. Statistical analysis revealed several important factors impacting outcome. CONCLUSIONS: Successful IT defined as prolonged patient and graft survival and TPN independence can be readily achieved in select patients with IF and complications related to TPN therapy. Outcomes have improved with experience gained and control of viral infections and rejection.

Adolescent↗
PubMed2004

Induction therapy with interleukin-2 receptor antagonist after intestinal transplantation is associated with reduced acute cellular rejection and improved renal function.

PURPOSE: To determine the effectiveness of induction immunotherapy with interleukin-2 receptor antagonists (IL2RA) after intestinal transplantation (IT). METHODS: A single-center, retrospective study was undertaken of all patients undergoing IT using existing medical records and database. Immunotherapy was either triple (standard maintenance triple therapy [SMTT]) or IL2RA [induction IL2RA plus SMTTx] or OKT3 [induction antilymphocyte preparations plus SMTTx]). Data was collected for the first 175 postoperative days. Outcomes included pretransplant renal function, posttransplant serum creatinine normalized to age (nl-sCR), rejection (ACR), and survival. Standard statistical analysis was undertaken. RESULTS: There were no significant differences in the groups: triple (n = 10, median age 3.5 years, cGFR 106 +/- 44 mL/min), IL2RA (n = 13, median age 3.2 years, cGFR 101 +/- 61 mL/min), OKT3 (n = 4, median age 7.7 years, cGFR 104 +/- 27 mL/min). nl-sCR was significantly (P <.01) lower in IL2RA at most postoperative weeks. IL2RA had significantly fewer rejection and infectious episodes than the other two groups. Three-year patient survival was 92% in IL2RA versus 50% triple and OKT3. CONCLUSIONS: IL2RA immunotherapy after IT is associated with a lower incidence of renal dysfunction as compared with historical controls. Furthermore, IL2RA therapy resulted in a lower incidence of rejection and improved survival. IL2RA should be considered in select patients undergoing IT.

Child↗
PubMed2003

Biliary complications after adult living donor liver transplantation.

We evaluated the causes and outcomes of biliary complications occurring after adult living donor liver transplantation (ALDLT) in a large patient cohort. Among 46 patients who underwent ALDLT at two different centers early bile duct complications occurred in 11 recipients (23.9%), consisting of leakage from the anastomotic site or from the cut surface of the liver. T-tube-associated biliary complications occurred in four patients. Late complications, primarily anastomotic strictures, occurred in 15 patients (32.6%) at 6.7+/-3.5 months after transplantation. Surgical intervention was generally required for early biliary complications but rarely necessary for late complications. No graft loss was caused by biliary complications. Thus, ALDLT is accompanied by a high rate of biliary complications, which in our series have been of low severity. However, long-term effects on graft function are not yet known.

Adult↗
PubMed2003

Biliverdin protects rat livers from ischemia/reperfusion injury.

OBJECTIVE: To explore putative cytoprotective functions of biliverdin during hepatic ischemia/reperfusion (I/R) injury in rat models. MATERIAL AND METHODS: Male Sprague Dawley (SD) rat livers were harvested and stored for 24 hours at 4 degrees C in University of Wisconsin (UW) solution (n=18), and then perfused with blood for 2 hours on an isolated rat liver perfusion apparatus equipped for temperature (37 degrees C), pressure (13 cm H2O), and pH (7.3) maintenance. Biliverdin was added to the blood at concentrations of 10 and 50 micromol in two groups of six animals. Portal vein blood flow, bile production, and GOT/GPT levels were assessed serially. At the conclusion of the experiment, liver samples were collected for histologic evaluation using Suzuki criteria. RESULTS: BV exerted protective effects against liver I/R injury. Adjunctive biliverdin improved portal venous blood flow (mL/min/g) from the beginning of reperfusion (1.33+/-0.17 versus 0.98+/-0.15; P<.001) and increased bile production (mL/g) as compared with the control group (3.40 versus 1.88; P<.003). I/R-induced hepatocellular damage as measured by GOT/GPT release (IU/L) was diminished in the biliverdin group (91 versus 171 and 46 versus 144, respectively; P<.0001). Improved liver function by biliverdin was accompanied by preservation of the histologic structure as assessed by Suzuki criteria (3.7+/-1.4 versus 6.8+/-0.8 in untreated controls; P<.005). CONCLUSIONS: Biliverdin attenuates the ischemia/early reperfusion injury of rat liver grafts as assessed by hemodynamics, function, enzyme analysis, and histology. This study provides the rationale for novel therapeutic approaches using biliverdin to maximize the organ donor pool through the safer use of liver transplants despite prolonged periods of cold ischemia.

Alanine Transaminase↗
PubMed2003

[Adult living donor liver transplantation. Analysis of the first 30 cases].

INTRODUCTION: In the last 2-3 years, adult living donor liver transplantation (ALDLT) has been developed on an international scale, multiplying the number of procedures performed. Despite this, analysis of the results is still incomplete. The aim of the present study was to perform a descriptive analysis of the results after the first 3 years of the initiation of the program. MATERIAL AND METHODS: During this period, 30 ALDLT were performed. In all procedures, right lobe grafts were used. The mean age of donors and recipients was 31.8 and 52.7 years, respectively. The main indication for liver transplantation was liver cirrhosis due to hepatitis C virus (70%) and 38% of recipients were stage C in the Child-Pugh classification. A total of 46.7% of recipients had hepatocellular carcinoma. RESULTS: Donors: The mean volume of the remnant liver was 632 cc (40.5% of the previous hepatic mass). Ten donors (33%) presented complications. The most frequent complication was biliary fistula (20%) and three patients required reintervention. The mean length of hospital stay among donors was 11.7 days. Recipients: The mean weight of the graft was 775 g, with a mean difference between graft weight and that of the recipient of 1.11. Fifteen recipients (50%) presented biliary leaks and nine of these (30%) required reintervention. There were no graft losses for technical reasons. Four patients died. With a median follow-up of 14 months, actuarial survival at 18 months was 92.9%. CONCLUSION: ALDLT is an effective method for reducing the number of patients on the waiting list. The probability of survival is similar to that of cadaveric transplantation. Biliary complications in the recipient constitute a problem, the long-term repercussions of which remain to be resolved.

Adolescent↗
PubMed2000

Bleeding risk factors in chronic oral anticoagulation with acenocoumarol.

We studied major bleeding complications, death related to hemorrhage, and tried to identify predisposing factors for bleeding in outpatients treated with acenocoumarol. We evaluated 811 outpatients attending a specialized anticoagulant therapy unit. The intended INR range was 3.5-4.5 for mechanical heart valve replacement (N= 384) and 2.0-3.0 for other indications (N= 427). The variability of INR for the total follow-up and the 2 months before the hemorrhage was calculated. The total follow-up was 1,963.26 years with 27,321 control tests. We observed 47 major bleeding episodes, including 2 fatal (central nervous system hemorrhages), in 37 patients. 49.5% of the patients had underlying diseases. The rate of major and fatal hemorrhage was 2.39 and 0.10 episodes per 100 patients year, respectively. Hemorrhagic complications were more frequently observed in patients with a more intense intended range (8.2% in the INR 3.5-4.5 group vs. 1.5% in the 2.0-3.0 INR group). The risk of major bleeding increased in patients with an achieved INR higher than 6 and in those with higher INR variability during follow-up. The estimated probability of bleeding also increased with time: it was 0.102% at 78 months, and at the beginning of therapy it was 0.006% and 0.007% at 1 and 4 months, respectively. The intensity of anticoagulation and the deviation of the INR from the target are the most important risk factors for bleeding in patients taking acenocoumarol. Monitoring the variability of INR can help identifying patients predisposed to bleeding. However, the screening for underlying disease should always be performed.

Acenocoumarol↗
PubMed1999

Prognostic factors in nonresectable pancreatic adenocarcinoma: a rationale to design therapeutic trials.

OBJECTIVE: Most patients with pancreatic cancer show an advanced tumor at the time of diagnosis. In recent years, new therapies have been developed in such patients, thus forcing the analysis of factors that influence their survival. The present study was aimed at determining the prognostic factors in a series of 134 consecutive patients with pancreatic carcinoma not suitable for surgical resection, due to either locally advanced tumors or metastatic spread. METHODS: First, 34 epidemiological, clinical, analytical, and tumor-related parameters recruited at admission were included in a univariate analysis of survival by using the Kaplan-Meier method. Those significant variables in the previous step were thereafter introduced in a Cox regression procedure. A prognostic index for calculating the relative risk of death of each patient was also proposed. RESULTS: The median survival time in the whole series was 3.11 months, the 3, 6, and 12 months probability of survival being 51%, 28%, and 8%, respectively. Eight of 34 variables (jaundice and toxic syndrome at admission, serum cholesterol, iron and alanine aminotransferase concentrations, leukocyte count, baseline performance status, and the presence of distant metastases) were selected in the univariate analysis. Of these eight parameters, the Cox regression analysis identified a preserved baseline performance status (OR = 2.14, 95% CI = 1.49-3.04) and the absence of metastases (OR = 1.34, 95% CI = 1.03-1.73) as the only variables independently associated with a longer survival. Therefore, a prognostic index was constructed allowing the division of patients in three different groups according to their relative risk of death (RRD) = exp (performance status x 0.7589 + presence of metastases x 0.2891). CONCLUSIONS: The results of the present investigation suggest that baseline performance status and distant metastases should be considered in designing and evaluating any therapeutic trial in patients with nonresectable pancreatic carcinoma.

Adenocarcinoma↗