Álvarez-Cienfuegos, J. (Javier)

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    Risk factors for recurrence of hepatitis C after liver transplantation.
    (Wiley-Blackwell, 1998) Civeira, M.P. (María Pilar); Peña, A. (Andrés) de la; Álvarez-Cienfuegos, J. (Javier); Sola, J. (Josu); Sangro, B. (Bruno); Prieto, J. (Jesús); Herrero, J.I. (José Ignacio); Garcia, N. (Nicolás); Quiroga, J. (Jorge)
    Recurrent hepatitis C is a frequent complication after liver transplantation for hepatitis C virus– related cirrhosis, but risk factors related to its development remain ill defined. Twenty-three patients receiving a primary liver graft for hepatitis C virus–related cirrhosis and with an assessable biopsy performed at least 6 months after liver transplantation were studied retrospectively. The end point of this study was to look for risk factors associated with the development of histologic hepatitis C in the graft. Thirty-six major variables were studied, and those reaching significance by univariate analysis were included in a multivariate analysis. Eighteen patients (78%) developed posttransplant hepatitis C. On univariate analysis, six variables showed significant predictive value: increased immunosuppression for treatment of acute rejection; pretransplant hepatocellular carcinoma; cumulative doses of prednisone at 3, 6, and 12 months after transplantation; and mean blood trough levels of cyclosporine in the first 6 months posttransplantation. On multivariate analysis, two variables retained independent statistical significance as predictors of hepatitis C recurrence, namely receipt of antirejection therapy (P 5 .0087) and lower mean cyclosporine levels in the first 6 months after transplantation (P 5 .0134). Therefore, recurrence of hepatitis C after liver transplantation seems to be at least partially related to posttransplantation immunosuppressive therapy.
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    ¿Es razonable el abordaje laparoscópico en patología maligna colo-rectal?
    (Universidad de Navarra, 1999) Baixauli-Fons, J. (Jorge); Pardo, F. (Fernando); Álvarez-Cienfuegos, J. (Javier); Hernandez-Lizoain, J.L. (Jose Luis); Diez-Caballero, A. (Alberto); Martínez-Barrera, J. (Jorge)
    Desde que se efectuó la primera resección de colon por vía laparoscópica en 1990, han sido publicados numerosos artículos, manifestándose diferentes opiniones, algunas de ellas francamente contrapuestas, en cuanto a validez o no de esta vía de abordaje quirúrgico, para el tratamiento del cáncer colo-rectal. El presente estudio de revisión pretende poner en claro cuál es la situación actual de la resección de colon por vía laparoscópica. Se analizan las ventajas e inconvenientes de dicho tratamiento, haciendo especial hincapié en situar la realidad actual de la incidencia de metástasis en el orificio de entrada de los trócares, así como, analizar las posibles causas. Se estudia la importancia de la experiencia del equipo quirúrgico y de la curva de aprendizaje para obtener los mejores resultados. Así como la necesidad de mantener las normas establecidas para una correcta resección de intestino grueso desde el punto de vista oncológico y la importancia de efectuar este tipo de cirugía dentro de ensayos clínicos controlados.
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    Concurrent clarithromycin and cyclosporin A treatment
    (Oxford University Press, 1998) Álvarez-Cienfuegos, J. (Javier); Lopez-de-Ocariz, A. (A.); Sadaba, B. (Belén); Quiroga, J. (Jorge); Azanza, J.R. (José Ramón)
    Although macrolides have been associated with significant pharmacokinetic interactions, clarithromycin is considered to have a low interaction capacity. In this study, six transplant recipients treated with cyclosporin A also received clarithromycin. In all patients, the dose of cyclosporin A had to be reduced by a mean of 33% per day depending on the macrolide dose. Normalization of the dosage parameters began on the fourth day after stopping clarithromycin treatment. Co-administration of cyclosporin A and clarithromycin may lead to increases in whole blood cyclosporin levels, and appropriate dose reductions should be considered.
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    Liver transplantation in cirrhotic patients with diabetes mellitus: Midterm results, survival, and adverse events
    (Wiley-Blackwell, 2001) Pardo, F. (Fernando); Álvarez-Cienfuegos, J. (Javier); Gomez-Manero, N. (Noemí); Sangro, B. (Bruno); Prieto, J. (Jesús); Herrero, J.I. (José Ignacio); Quiroga, J. (Jorge); Blanco, J.J. (Jose J.)
    Liver cirrhosis is frequently associated with diabetes mellitus (DM), and this metabolic complication is also frequent after orthotopic liver transplantation (OLT). The aim of our study is to investigate which factors are associated with DM before and after OLT and their impact on post-OLT evolution. We evaluated the prevalence of DM among 115 liver transplant candidates with cirrhosis and assessed their evolution after OLT (median follow-up, 41 months). Sixteen candidates had DM requiring pharmacological therapy (group A), 45 candidates had DM controlled with diet (group B), and 54 candidates did not have DM (group C). One-year and 3-year actuarial survival rates were 100% and 100% for group A, 91% and 85% for group B, and 77% and 74% for group C, respectively (P <.03). Post-OLT DM was more frequent in group A. The incidence of other metabolic complications, major infections, rejection, and arterial hypertension; the need for hospitalization; and renal and graft function of patients in groups A, B, and C were similar. The only risk factor for DM 1 year after OLT on multivariate analysis was pre-OLT DM requiring pharmacological treatment. The incidence of complications, need for hospitalization, and renal and graft function 1 year after OLT for patients with post-OLT DM were similar to those of patients without post-OLT DM. In conclusion, patients with cirrhosis who have DM have a greater risk for post-OLT DM, but their midterm survival is not worse than the survival of those without DM.
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    Comparison Between Two Warm Ischemic Models in Experimental Liver Transplantation in Pigs
    (Elsevier, 2003) Rotellar, F. (Fernando); Espi, A. (A.); Martinez-Regueira, F. (Fernando); Baixauli-Fons, J. (Jorge); Pardo, F. (Fernando); Olea, J. (J.); Álvarez-Cienfuegos, J. (Javier); Hernandez-Lizoain, J.L. (Jose Luis); Diez-Caballero, A. (Alberto); Nwose, P. (P.)
    Experimental models of warm ischemia in liver transplantation have been employed to study the mechanisms and treatment of ischemia reperfusion injury. METHODS: We compared a control group without (group A, n = 10) versus two models of warm ischemia of liver transplants in pigs: namely, occlusion of the hepatic artery and portal vein for 30 minutes (group B, n = 23) and extraction of the liver 60 minutes after cardiac arrest (group C, n = 5). Liver function tests, coagulation studies, and liver biopsies were performed during the first 24 hours post-liver transplant. RESULTS: Clamping of the hepatic vasculature in group B produced a significant liver injury compared with the control group: elevation of the ALT and an abnormal 1-hour post-revascularization biopsy similar to that observed in the cardiac arrest group C. The transaminase levels were lower among group A animals (P <.05). But the hepatic synthetic functions as reflected in the protrombin time (PT) were not affected in group B versus group A. The alteration in PT with respect to the initial value was similar among group A and group B animals, which were significantly less than that in group C (P <.05). CONCLUSIONS: Occlusion of the hepatic artery and portal vein, a simple surgical maneuver, causes moderate damage to a liver graft but less alteration of hepatic synthetic function. Clamping of the hepatic vasculture obtains more long-term survivors after OLT than cardiac arrest.
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    Role of the extended lymphadenectomy in gastric cancer surgery: experience
    (Springer Verlag, 2003) Martinez-Gonzalez, M.A. (Miguel Ángel); Martinez-Regueira, F. (Fernando); Pardo, F. (Fernando); Álvarez-Cienfuegos, J. (Javier); Hernandez-Lizoain, J.L. (Jose Luis); Sierra, A. (Alejandro)
    Although curative resection is the treatment of choice for gastric cancer, controversy exists about the adequate extent of lymph node dissection when resection is performed. METHODS: We retrospectively assessed 85 patients who underwent a limited lymphadenectomy (D1) and 71 who had an extended lymph node dissection (D2) in a single institution between 1990 and 1998 (median follow-up, 37.3 months). Prognostic factors were assessed by Cox proportional hazard models adjusted for potential confounders. RESULTS: We found no significant difference in the length of hospital stay (median, 12.1 and 13.1 days), overall morbidity (48.2% and 53.5%), or operative mortality (2.3% and 0%) between D1 and D2, respectively. Five-year survival in the D2 group was longer (50.6%) than in the D1 group (41.4%) for tumor stages (tumor-node-metastasis) >I. In multivariate analysis, tumor-node-metastasis stage (hazard ratio for stages >I vs. 0-I, 11.6), the ratio between invaded and removed lymph nodes, the presence of distant metastases, Lauren classification, and the extent of lymphadenectomy (hazard ratio for D1 vs. D2, 2.3; 95% confidence interval, 1.25-4.30) were the only significant prognostic factors. CONCLUSIONS: Our experience shows that extended (D2) lymph node dissection improves survival in patients with resected gastric cancer.
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    Increased adipose tissue expression of lipocalin-2 in obesity is related to inflammation and matrix metalloproteinase-2 and metalloproteinase-9 activities in humans
    (Elsevier Scientific Pub, 2009) Rotellar, F. (Fernando); Ramirez, B. (Beatriz); Catalan, V. (Victoria); Álvarez-Cienfuegos, J. (Javier); Frühbeck, G. (Gema); Silva, C. (Camilo); Gomez-Ambrosi, J. (Javier); Salvador, J. (Javier); Rodriguez, A. (Amaia); Gil, M.J. (María José)
    Abstract Lipocalin-2 (LCN2) is a novel adipokine with potential roles in obesity, insulin resistance, and inflammation. The aim of the present work was to evaluate the effect of obesity on circulating concentrations and gene and protein expression levels of LCN2 in human visceral adipose tissue (VAT) as well as its involvement in inflammation. VAT biopsies from 47 subjects were used in the study. Real-time PCR and Western-blot analyses were performed to quantify levels of LCN2 in VAT as well as the association with other genes implicated in inflammatory pathways. Forty-four serum samples were used to analyze the circulating concentrations of LCN2. Zymography analysis was used to determine the activity of matrix metalloproteinase (MMP) in VAT. Obese patients exhibited increased mRNA (p<0.0001) and protein (p=0.017) expression levels of LCN2 compared to lean subjects. Although no differences in plasma LCN2 concentrations were observed, increased circulating LCN2/MMP-9 complex levels were found (p=0.038) in the obese group. Moreover, obese individuals showed increased (p<0.01) activity of MMP-2 and MMP-9/LCN2 complex, while a positive correlation (p<0.01) between MMP-2 and MMP-9 activities and BMI was observed. Gene and protein expression levels of LCN2 in VAT were positively associated with inflammatory markers (p<0.01). These findings represent the first observation that mRNA and protein levels of LCN2 are increased in human VAT of obese subjects. Furthermore, LCN2 is associated with MMP-2 and MMP-9 activities as well as with proinflammatory markers suggesting its potential involvement in the low-grade chronic inflammation accompanying obesity.
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    Pancreatectomía central en tumores benignos del cuello del páncreas
    (Elsevier España, 2005) Valenti, V. (Víctor); Pastor, C. (Carlos); Rotellar, F. (Fernando); Poveda, I. (Ignacio); Pardo, F. (Fernando); Álvarez-Cienfuegos, J. (Javier); Beunza, J.J. (Juan José); Gil, A. (Aurora); Cervera, M. (María)
    The surgical treatment of benign tumors of the neck of the pancreas usually consists of enucleation or formal pancreatectomy. Central pancreatectomy has been put forward because it has fewer major complications and can preserve endocrine and exocrine function. Between January 1999 and march 2003, three patients with benign tumors of the neck of the pancreas underwent central pancreatectomy. all patients underwent computed tomography scans, intraoperative ultrasound and frozen-section analysis. pathologic examination showed two mucinous cystadenomas and one serous cystadenoma. after a mean follow-up of 34 months, none of the patients has shown major complications or local recurrence, or has developed diabetes. In conclusion, central pancreatectomy is a useful technique for selected benign or low-grade malignant pancreatic tumors of the neck of the pancreas.
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    Effect of treatment with tranexamic acid on complement activation and ischemia reperfusion in liver transplantation in pigs
    (Elsevier, 1999) Martinez-Regueira, F. (Fernando); Pardo, F. (Fernando); Álvarez-Cienfuegos, J. (Javier); Hernandez-Lizoain, J.L. (Jose Luis); Sierra, A. (Alejandro); Diez-Caballero, A. (Alberto); Nwose, P. (P.)
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    Effect of guanylin peptides on pancreas steatosis and function in experimental diet-induced obesity and after bariatric surgery
    (2023) Valenti, V. (Víctor); Otero, A. (Aarón); Catalan, V. (Victoria); Álvarez-Cienfuegos, J. (Javier); Becerril, S. (Sara); Frühbeck, G. (Gema); Burrell, M.A. (María Ángela); Martín-Rodríguez, M. (Marina); Gomez-Ambrosi, J. (Javier); Rodriguez, A. (Amaia); Moncada-Durruti, R. (Rafael)
    Introduction: Obesity contributes to ectopic fat deposition in non-adipose organs, including the pancreas. Pancreas steatosis associates with inflammation and beta-cell dysfunction, contributing to the onset of insulin resistance and type 2 diabetes. An improvement of pancreatic steatosis and indices of insulin resistance is observed following bariatric surgery, but the underlying mechanisms remain unknown. We sought to analyze whether guanylin (GUCA2A) and uroguanylin (GUCA2B), two gut hormones involved in the regulation of satiety, food preference and adiposity, are involved in the amelioration of pancreas fat accumulation after bariatric surgery. Methods: Pancreas steatosis, inflammation, islet number and area were measured in male Wistar rats with diet-induced obesity (n=125) subjected to surgical (sham operation and sleeve gastrectomy) or dietary (pair-fed to the amount of food eaten by gastrectomized animals) interventions. The tissue distribution of guanylate cyclase C (GUCY2C) and the expression of the guanylin system were evaluated in rat pancreata by real-time PCR, Western-blot and immunohistochemistry. The effect of guanylin and uroguanylin on factors involved in insulin secretion and lipogenesis was determined in vitro in RIN-m5F beta-cells exposed to lipotoxic conditions. Results: Sleeve gastrectomy reduced pancreas steatosis and inflammation and improved insulin sensitivity and synthesis. An upregulation of GUCA2A and GUCY2C, but not GUCA2B, was observed in pancreata from rats with dietinduced obesity one month after sleeve gastrectomy. Interestingly, both guanylin and uroguanylin diminished the lipotoxicity in palmitate-treated RIN-m5F beta-cells, evidenced by lower steatosis and downregulated lipogenic factors Srebf1, Mogat2 and Dgat1. Both guanylin peptides reduced insulin synthesis (Ins1 and Ins2) and release from RIN-m5F beta-cells, but only guanylin upregulated Wnt4, a factor that controls beta-cell proliferation and function. Discussion: Together, sleeve gastrectomy reduced pancreatic steatosis and improved beta-cell function. Several mechanisms, including the modulation of inflammation and lipogenesis as well as the upregulation of GUCA2A in the pancreas, might explain this beneficial effect of bariatric surgery.