Francisco Arnal

Universidade da Coruña

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Alejandra Otero

Complexo Hospitalario Universitario A Coruña

Francisco Suárez

Universidade da Coruña

J. L. Vázquez-Iglesias

Complexo Hospitalario Universitario A Coruña

Rafael Máñez

Bellvitge University Hospital

Javier Aguirrezabalaga

Complexo Hospitalario Universitario A Coruña

J. Durana

Hospital San Juan de la Cruz

Maria J. Lorenzo

Banc de Sang i Teixits

Javier Pereira

Universidade da Coruña

M Gómez-Gutiérrez

Pontificia Universidad Javeriana

José M. Vázquez

Government of the United States of America

Cooperative Institutions

Complexo Hospitalario Universitario A Coruña

Hospital San Juan de la Cruz

Universidade da Coruña

Instituto de Investigación Biomédica de A Coruña

Servicio Gallego de Salud

Hospital Universitario Virgen de la Arrixaca

Hospital Central de la Cruz Roja San José y Santa Adela

Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas

Hospital Clínic de Barcelona

Hospital General Universitario Gregorio Marañón

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Liver transplantation from Maastricht category 2 non-heart-beating donors

Transplantation (2003)

Alejandra Otero Manuel Gómez-Gutiérrez Francisco Suárez Francisco Arnal Antón Fernández-García

Background. The demand for liver transplantation has increasingly exceeded the supply of cadaver donor organs. Non-heart-beating donors (NHBDs) may be an alternative to increase the cadaver donor pool. Methods. The outcome of 20 liver transplants from Maastricht category 2 NHBDs is compared with 40 liver transplants from heart-beating donors (HBDs). After unsuccessful cardiopulmonary resuscitation (CPR), cardiopulmonary support (CPS) with simultaneous application of chest and abdominal compression (n=6), and cardiopulmonary bypass (CPB; n=14), which was hypothermic (n=7) or normothermic (n=7), were used to preserve the organs from NHBDs. Factors that may influence the outcome of livers from Maastricht category 2 NHBDs were also investigated. Results. With a minimum follow-up of 2 years, actuarial patient and graft survivals with livers from Maastricht category 2 NHBDs were 80% and 55%, respectively. Transplantation of organs from these donors was associated with a significantly higher incidence of primary nonfunction, biliary complications, and more severe initial liver dysfunction compared with livers from HBDs. Graft survival was 83% in livers from NHBDs preserved with CPS and 42% in those maintained with CPB. No graft failed if the duration of warm ischemia did not exceed 130 min with CPR or CPS, and if the period of CPB did not surpass 150 min when this method was used after CPR, regardless if it was hypothermic or normothermic. Conclusion. Livers from Maastricht type 2 NHBDs may be used for transplantation if the period of warm ischemia during CPR or CPS does not exceed 130 min. Hypothermic or normothermic CPB after CPR preserves liver viability for an additional 150 min.

10.1097/01.tp.0000085043.78445.53

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Citations (117)

Biliary Complications After Liver Transplantation From Maastricht Category-2 Non-Heart-Beating Donors

Transplantation (2008)

Francisco Suárez Alejandra Otero Miguel Solla Francisco Arnal Maria J. Lorenzo

Background. There are unresolved issues regarding the security of liver transplantation with non-heart-beating donors (NHBDs). Recently, an increased incidence of biliary complications, mainly intrahepatic ischemic-type biliary strictures, has been described after controlled NHBDs. Methods. We studied the incidence and risk factors for biliary complications among uncontrolled NHBDs recipients compared with a large population of HBD recipients. Results. Overall, 16.8% of patients in the HBD group and 41.7% of patients in the NHBD group suffered any type of biliary complication (P=0.66). However, the incidence of nonanastomotic biliary strictures was significantly greater in the NHBD group (P<0.001). Multivariate analysis showed that independent risk factors for nonanastomotic strictures were hepatic artery thrombosis (relative risk; 98.7) and receiving a liver from a NHBD (relative risk; 47.1). Conclusions. If this type of donors is accepted as a source of liver organs, the high incidence of biliary complications should be considered and efforts should be made to decrease ischemic injury.

10.1097/01.tp.0000297945.83430.ce

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Citations (117)

Retransplantation for hepatitis c–related cirrhosis under long-term pegylated interferon therapy

Transplantation Proceedings (2004)

Francisco Suárez Alejandra Otero Benito Gonzalez M Gómez-Gutiérrez Francisco Arnal

Pegylated interferon

Hepatitis C

Immunosuppression

10.1016/j.transproceed.2004.03.028

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Citations (1)

Development of an Information System for Multicenter Epidemiologic Studies on Cancer

José M. Vázquez Isabel Martínez-Lage Macías López B. González-Conde Francisco Arnal

Cancer is caused by a variety of factors whose study requires a large amount of data. Compiling these data is an expensive and time-consuming task which can be carried out in a better way with the support of Information and Communication Technologies (ICT). However, most epidemiologic studies take place without this support of informatics or with basic tools that are developed by unqualified professionals. As a consequence, the integrity of the compiled data cannot be guaranteed, and the reliability of the studies is affected. This work presents an Information System (IS) for the development of multicenter epidemiologic studies on cancer which has been successfully applied to the execution of an epidemiologic study of colorectal cancer in Galicia, Spain.

10.1109/itab.2007.4407366

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Citations (2)

Jejunal leiomyosarcoma, a rare cause of obscure gastrointestinal bleeding diagnosed by wireless capsule endoscopy

Surgical Endoscopy (2004)

David Martı́nez-Ares Benito González-Conde Julián Yáñez E. Estévez Francisco Arnal

Gastrointestinal bleeding

Etiology

Submucosa

Obscure Gastrointestinal Bleeding

Jejunum

10.1007/s00464-003-4255-4

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Citations (7)

Reversal of Cardiac Cirrhosis Following Orthotopic Heart Transplantation

American Journal of Transplantation (2008)

María G. Crespo‐Leiro Olga Robles M.J. Paniagua Raquel Marzoa C. Naya

Contraindication

10.1111/j.1600-6143.2008.02227.x

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Citations (43)

MicroRNA profile and KRAS status in metastatic colorectal cancer.

Journal of Clinical Oncology (2011)

Manuel Valladares‐Ayerbes M. Blanco Margarita Reboredo María José Lorenzo-Patiño Francisco Arnal

453 Background: microRNAs (miRNAs) are small non-coding RNA with regulatory functions. miRNAs expression is deregulated in cancer. Our objective is to establish a miRNA expression profile as a prognostic and predictive signature in Colorectal Cancer (CRC). In this cohort, patients with metastatic (m) CRC have been included. The expression of miRNAs have been analyzed and correlated with clinical and pathologic parameters, including KRAS status, disease free survival (DFS), and overall survival (OS). Methods: Tissue samples of mCRC were obtained as formalin-fixed paraffin-embedded (FFPE) specimens from the archives of our institution, after obtaining informed consent of patients. Genomic DNA was extracted using Qiaamp DNA mini kit (Qiagen). For the mutational testing of KRAS gene, we use the TheraScreen KRAS PCR kit (Qiagen). miRNA-enriched RNA was extracted using High Pure miRNA Isolation Kit (Roche). miRNA expression was analyzed by quantitative reverse transcription PCR (RT-qPCR) using LNA technology (Exiqon) in a LightCycler 480 (Roche) device. REST2009 (Qiagen), SPSS 19 (IBM), and Prism (GraphPad) software was used to data analysis. Results: One-hundred and forty mCRC patients have been included. To date, we have extracted DNA and performed KRAS mutational testing for 127 FFPE specimens. From these, 72 (56.7%) were wt while the remaining 55 (43.3%) were mt. We have performed a miRNA expression studies in 28 tumors. miRNAs let-7a, miR-17, miR-21, and miR-200c were analyzed. 5S rRNA and U6 snRNA were amplified as reference genes. miR-21, miR-17, and let-7a were found upregulated (p<0.05) in mCRC samples versus healthy colon. However, for all 4 miRNAs analyzed, there were no significant differences of expression between wt and mt tumor samples for KRAS gene. Conclusions: The expression of 4 miRNAs analyzed is not correlated with mutations in KRAS gene. However, 3 of 4 miRNAs analyzed were found upregulated in tumors. The results for the association of the expression of miRNAs analyzed with the response to treatment and other clinical parameters will be presented during the symposium. Supported in part by SERGAS, Xunta de Galicia, Grant PS08/77. No significant financial relationships to disclose.

10.1200/jco.2011.29.4_suppl.453

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[Biology of micro-vascularized cartilaginous transplantation in the growing dog].

PubMed (1985)

Luc Téot Francisco Arnal C Humeau H Vannereau Pous Jg

Epiphyseal bone transplantations including growth area have been extensively studied experimentally in different animals and applied in children for several decades. Results were unpredictable and the amount of growth obtained with the graft could get 50 per cent of the normal. Development of microsurgical techniques has determined new possibilities of epiphyseal transfer with the respect of the epiphyseal vascularization. Growth plate germinal cell division is directly related to the epiphyseal vascular respect. In a large multifacetted program we could successively determine the vascular patterns of the donor site areas and then utilized different grafts in some experimental situations reproducing the clinical pathology in children, like hip dysplasia or epiphyseal defects after resection for tumor or infection. Results demonstrate that the main problem, in epiphyseal transplantation, is not vascular but mechanical. Further studies have to be done in this direction.

Epiphyseal plate

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[Experimental model of auxiliary heterotopic liver-intestinal transplantation]

Javier Bueno E López Ann Centeno Carmen Ramil Luis García‐Alonso

In pigs, orthotopic liver-intestine transplantation (LITX) has high per operative morbidity and mortality. It is due to hemodynamic, coagulation and metabolism disorders during native liver hepatectomy (total hepatic vascular exclusion) and the postoperative diarrhea secondary to initial dysfunction of the graft and enterectomy of native intestine. To avoid those disturbances and to increase the survival, we have developed a porcine model of auxiliary heterotopic LITX. The allograft was harvested in-bloc, containing the liver, duodenum, pancreas, and jejunum. In the recipient, the liver and intestine were left intact. The allograft was implanted heterotopically, caudal to the native liver. Venous drainage was achieved with anastomosis of donor (D) to recipient (R) infrahepatic cava; and arterialization with anastomosis of D aortic conduit containing the celiac axis and SMA to infra-renal R aorta. The D jejunum was hooked-up to R jejunum. The experiment was performed in 16 animals without intraoperative deaths, hemodynamic stability and no blood requirements. Four animals were left alive 7 days with functioning grafts, suggesting the model viability.

Jejunum

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MicroRNAs and response to anti-EGFR therapy in metastatic colorectal cancer.

Journal of Clinical Oncology (2012)

M. Blanco Mar Haz‐Conde Teresa Rodríguez‐Rigueiro Angélica Figueroa Margarita Reboredo

e21002 Background: The discovery of KRAS gene as response predictive factor to anti-EGFR antibodies supposed a revolution in the pharmacological management of metastatic colorectal cancer (mCRC) patients (pts), since only KRAS native (WT) pts are possible responders (R) and susceptible to be treated with this targeted therapy. However, the appearance of non-responders (NR) among KRAS WT pts during the administration of anti-EGFR therapy has stimulated the research in additional predictive markers. Here, we explore the putative role of microRNA (miRNA) deregulation as predictive tool of response to anti-EGFR therapy in mCRC pts. Methods: Tissue samples of mCRC were obtained as formalin-fixed paraffin-embedded (FFPE) specimens from the archives of our institution, after obtaining informed consent of pts. Genomic DNA was extracted using Qiaamp DNA mini kit (Qiagen). For the mutational testing of KRAS gene, we use the TheraScreen KRAS PCR kit (DxS, Qiagen). miRNA-containing total RNA was extracted using Tripure (Roche). miRNA expression was analyzed by SYBR-green-based RT-qPCR in a LightCycler 480 (Roche) device using the Human Cancer RT2 miRNA PCR array (SABiosciences, Qiagen). First data analysis was performed with the application provided by supplier (SABiosciences, Qiagen). Bioinformatic analyses were performed in miRBase 18, TargetScanHuman 6.0 and TarBase 6.0 databases. Additional statistical analyses were performed on R 2.14 (R Foundation), SPSS 19 (IBM) and Prism (GraphPad). Results: We analyze 9 primary colon cancer and 3 non-matched normal adjacent (NAT) tissues. Tumor samples corresponded to 6 KRAS WT and 3 KRAS mutated pts. Among KRAS WT pts, 3 had shown response to anti-EGFR antibodies and 3 did not. Samples were analyzed in duplicate for the expression of 88 cancer-related miRNAs. We found 22 miRNAs significantly (p<0.01) upregulated (>4-fold) when comparing KRAS WT NR versus R pts. From these 22 miRNAs, we detected only 6 when we search in databases for experimentally tested or predicted miRNA interactions with KRAS. Conclusions: We found a miRNA signature which could be utilized as response predictive tool for anti-EGFR therapy in mCRC pts. Further analysis will be necessary to establish the performance of this signature.

MiRBase

10.1200/jco.2012.30.15_suppl.e21002

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