Search

Extended criteria donor livers are increasingly being accepted for transplant in an attempt to bridge the gap between the number of patients on the waiting list and the number of available donor livers. Our objective was to describe our first case of hepatic resuscitation by means of an ex situ perfusion machine in hypothermia with oxygen insufflation of a liver graft extracted from a donor in type 3 asystole after regional perfusion in normothermia.A 53-year-old woman with disabling polycystic liver disease was included on the liver transplant waiting list. Donation was offered in type 3 asystole with regional perfusion in normothermia. Given that it was an elderly donor with a low-weight graft, hepatic resuscitation was decided by means of an ex situ perfusion machine in hypothermia with oxygen insufflation.After performing the bench work, the injector is selectively cannulated via the portal to connect it to the hypothermic perfusion machine. The average temperature of the perfusate (3 L modified Belzer) was 10°C for 120 minutes at 250 mL/min. The implant was completed without the need for transfusion of blood products, postreperfusion Sd, or vasoactive support. Peak of GOT/GPT was 803/276 at 24 hours posttransplant.

An organ shortage is the reason why it is necessary to expand the pool of donors, which can be achieved by using elderly donors. The main goal of this study is to analyze the outcomes of liver transplant (LT) when it is performed with donors older than 75 years.We carried out a retrospective case-control study (N = 212) that included LTs with donors older than 75 years (group A, n = 106 cases) that were performed in our center between the years 2010 and 2020. This cohort has been paired off with a similar control group (group B, n = 106) whose donors were significantly younger. A survival analysis using the Kaplan-Meier model was performed.Average (SD) age of donors in group A was statistically greater than group B (A, 79.1 [3.0] years vs B, 54.4 [15.3], P.001). There were no differences either in the average age of the recipients or in the Model for End-Stage Liver Disease score of both groups. Indications for LT were distributed equally in both groups: the most common was cellular hepatocarcinoma followed by alcohol-related cirrhosis. Survival rates for group A were 81%, 78%, and 67%, in 1, 3, and 5 years, respectively, while in group B they were 85%, 76%, and 71%, respectively, without differences found between the groups (P = .57).Using elderly liver donors is safe, achieving good outcomes in terms of short- and midterm rates of survival.

INTRODUCTION Among the strategies designed to optimize the number of existing liver grafts for transplantation, the implementation of the graft assessment process is one of the least explored. The main objective is to identify the risk factors presented by liver donors for «NO validity». Secondly, we analyzed the coincidence between the surgeon's assessment and that of the anatomo-pathologist in the invalid donors. MATERIAL AND METHOD Retrospective study conducted from a prospective database that analyzes 190 liver donors, 95 valid and 95 NOT valid. The variables of each of them corresponding to the donation protocol of the National Transplant Organization are studied. Through a multivariate study we determine the independent risk factors of NO validity. We checked the causes of NO validity argued with the histopathological findings of these grafts. RESULTS The independent risk factors of non-validity in the multivariate study (P < .05) were: dyslipidemia, personal medical history other than cardiovascular and abdominal surgical risk factors, GGT, BrT, and the result of previous liver ultrasound. The 3 most frequent causes of NO validity were: steatosis, fibrosis and macroscopic appearance of the organ. 78% of the biopsies confirmed the NO validity of the graft (in 57.9% of the cases the histological findings coincided with those described by the surgeon). The 22.1% of the biopsies hadnt pathological findings. CONCLUSIONS The determination of the risk factors of NO validity will contribute to the design of future assessment scores that are useful tools in the process of liver graft assessment.).

Diagnosis of sinusoidal obstruction syndrome (SOS) after hematopoietic cell transplantation (HCT) is based on clinical criteria including weight gain, ascites, hepatomegaly, and jaundice.[1] However, clinical and histological features and prognosis of SOS after liver transplantation (LT) seem to differ from SOS after HCT.[2, 3] We aimed to determine the characteristics and outcomes of SOS after LT.

Introduction The greater survival of transplanted patients is accompanied by an increase in the rate of de novo malignancies (NM), which are the most frequent late-onset complication. We can distinguish between non-melanoma skin cancers (NMSC), post-transplant lymphoproliferative disorders (PTLD) and solid organ cancers (SOC). Our objective is to determine the incidence of the different types of NM, the time elapsed until diagnosis and survival rates in our setting. Methods We conducted a retrospective study of 1071 liver transplant patients from 1990 to 2015 at our center. We analyzed the demographic variables, incidence of NM and survival. Results 184 NM developed in 1071 transplant patients (17%), specifically 19% of the males and 13% of the females (P = .004). The most frequent NM were NMSC (29%), lung (18%), head and neck (16%), PTLD (10%) and gastrointestinal (8%). The median time of diagnosis was 7.9 years in NMSC, 3.9 years in PTLD and 9.8 years in SOC. Patients with NMSC had significantly better survival than those with PTLD or SOC. The incidence of de novo tumors (excluding NMSC) was 1889/100,000 transplants/year. By gender, lung cancer was the most common TOS in men and breast cancer in women. Conclusion In our setting, excluding NMSC, the incidence is 8.8 times greater than estimations for the general population, with a high rate of lung cancer, so we should implement preventive and diagnostic strategies.

espanolIntroduccion: el sindrome linfoproliferativo postrasplante (SLPT) es una complicacion infrecuente que ensombrece el pronostico de los pacientes sometidos a un trasplante hepatico (TH). Su patogenia es multifactorial, siendo sus dos principales factores de riesgo la inmunodepresion y la infeccion del virus de EpsteinBarr (VEB); sin embargo, en actualidad se piensa que puede estar relacionada con otros factores. Metodos: estudio observacional en el que hemos analizado de forma retrospectiva 851 casos que fueron sometidos a un trasplante hepatico, de los cuales diez casos han desarrollado un SLPT. Se han analizado sus caracteristicas clinicopatologicas y el tratamiento recibido. Resultados: la incidencia del SLPT ha sido del 1,2% (10/851) y el tiempo medio de presentacion desde el TH hasta el diagnostico, de 36 meses (rango 1,2-144 meses). El lugar de presentacion ha sido extranodal en todos los casos, siendo mas frecuente la localizacion intestinal. Siete casos presentaron un SLPT monomorfo, todos ellos linfomas diferenciados de celulas B. El 50% de la serie presento seronegatividad para el virus de Epstein-Barr. La supervivencia global ha sido del 50%. Entre estos pacientes, hemos observado tres casos de curacion completa, un caso de estabilizacion de la enfermedad y otro caso de recurrencia. Conclusion: el SLPT es una complicacion infrecuente que supone una amenaza para la vida del paciente. Para poder instaurar un diagnostico precoz y un tratamiento que pueda modificar el curso de la enfermedad, es fundamental la identificacion de los pacientes en riesgo. Englishntroduction: Post-transplant lymphoproliferative syndrome (PTLD) is a rare and potentially life-threatening complication after liver transplantation. The aim of this study was to analyze the clinicopathologic features related to PTLD in a single institution after liver transplantation. Methods: Observational study where we have retrospectively analyzed 851 cases who underwent liver transplantation. Ten cases have developed PTLD. Their clinical-pathological characteristics and the treatment received have been analyzed. Results: PTLD incidence was 1.2% (10/851). The mean time from liver transplantation to PTLD diagnosis was 36 months (range 1.2 to 144 months). PTLD localization was extranodal in all cases, the most frequent location being intestinal. Seven cases showed a monomorphic lymphoma which in all cases was differentiated B cell lymphomas. Fifty per cent of the series were seropositive for Epstein-Barr virus. Five patients were alive at the time of the review. Among these patients, we observed three cases of complete remission and two cases of disease stabilization. The death rate was higher in the first year after diagnosis of PTLD. Conclusion: PTLD is a rare complication after liver transplantation, but it may pose a threat to the life of a liver transplant recipient. It is essential to identify patients at risk, to establish an early diagnosis and treatment that can change the outcome of the disease.

Despite the development of new antineoplastic agents for the treatment of colorectal cancer (CRC), oxaliplatin and fluoropyrimidines remain the most commonly employed drugs for the treatment of both early and advanced disease. Intrinsic or acquired resistance is, however, an important limitation to pharmacological therapy, and the development of chemosensitization strategies constitute a major goal with important clinical implications. In the present work, we determined that high levels of activated Src kinase, measured as phospho-Src at the Tyr419 residue in CRC cell lines, can promote colorectal carcinoma cell resistance to oxaliplatin, but not to 5-fluorouracil (5FU), and that inhibition of this protein restores sensitivity to oxaliplatin. Similar results were observed with in vivo patient-derived xenograft (PDX) models that were orthotopically grown in murine livers. In PDX tumor lines derived from human CRC liver metastasis, dasatinib, a Src inhibitor, increases sensitivity to oxaliplatin only in tumors with high p-Src. However, dasatinib did not modify sensitivity to 5FU in any of the models. Our data suggest that chemoresistance induced by p-Src is specific to oxaliplatin, and that p-Src levels can be used to identify patients who may benefit from this combination therapy. These results are relevant for clinicians as they identify a novel biomarker of drug resistance that is suitable to pharmacological manipulation., The authors thank the donors and HUVR-IBiS Biobank (Andalusian Public Health System Biobank and ISCIII-Red de Biobancos PT13/0010/0056) for the human specimens used in this study. We also thank Jorge Martin-Perez for the generous gift of Src gene. The AC lab was supported by grants from the Spanish Ministry of Economy and Competitivity, Plan Nacional de I+D+I 2008-2011, Plan Estatal de I+D+I 2013-2016, ISCIII (Fis: PI12/00137, PI13/02295, PI15/00045, RTICC: RD12/0036/0028) co-funded by FEDER from Regional Development European Funds (European Union), Consejeria de Ciencia e Innovacion (CTS-1848) and Consejeria de Salud of the Junta de Andalucia (PI-0306-2012 and PI-0096-2014).

Resumen Introduccion Los nuevos metodos de ensenanza, basados en las nuevas tecnologias, ya adoptados en otros ambitos educativos y profesionales, se van introduciendo progresivamente en las facultades de medicina. El objetivo de nuestro estudio es presentar nuestra experiencia inicial en la implantacion de una asignatura de caracter semipresencial de fundamentos de cirugia. Material y metodos La asignatura se ha ofrecido con caracter voluntario a los estudiantes, y mantiene el grupo de ensenanza tradicional con un profesor responsable distinto. La asignatura se planifico con un porcentaje de virtualidad del 60% en la plataforma virtual WebCT y, posteriormente, en la plataforma Moodle. La asignatura virtual se estructuro en unidades tematicas, actividades academicamente dirigidas y herramientas de comunicacion. En la valoracion de la asignatura se presentan los informes realizados por la Unidad de Calidad de la Universidad de Cadiz (UCA). Resultados Se matricularon 32 alumnos en el curso 2005–2006 y 62 alumnos en el siguiente curso. El promedio de actividad en el aula virtual por alumno fue: 602 accesos, 13 temas de discusion propuestos en los foros y 20 correos intercambiados entre alumnos y profesores. Los alumnos que han cursado la asignatura han senalado que la virtualizacion de la asignatura la convierte en mas atractiva y contribuye a la adquisicion de conocimientos. Los datos del informe sobre la docencia han sido mejores que la media del departamento, la facultad de medicina y la UCA. Conclusiones La asignatura virtual de fundamentos de cirugia ha sido muy bien valorada dentro de nuestro ambito universitario. Pensamos que las herramientas docentes ofrecidas y los nuevos modelos de comunicacion contribuyen eficazmente a la ensenanza de la cirugia como disciplina dentro de la licenciatura de medicina.

Introduction The new methods of teaching, based on new technologies, already available in other educational and professional fields are gradually being introduced in our medical schools. The aim of our study is to present our initial experience in the introduction of a subject on the principles of surgery in our university. Material and methods The subject was offered voluntary to undergraduate students, with a maximum of 65 students per course during 2 consecutive academic years, while maintaining the traditional teaching with a formal lecture program with a different lecturer. The subject was designed with 60% virtuality on a WebCT platform and later in Moodle. The virtual subject was structured into teaching units, academically directed activities, and communication tools. The subject was assessed in a report prepared by Cadiz University Department of Evaluation and Quality. Results There were 32 students in the 2005-2006 course and 62 in the following course. The mean activity of the students was: 602 accesses, 13 subjects for discussion forums, and 20 e-mails between students and teachers. The students who participated in the virtual subject have remarked that virtualisation make it more attractive and is an aid in the acquisition of knowledge. The data obtained from the report showed better results than the mean obtained in other subjects of the Department, School of Medicine and Cadiz University. Conclusions The virtual subject of principles of surgery has been well evaluated in our university campus. We believe that the provision of teaching tools and new communication models make an effective contribution to the teaching of surgery as a subject in the school of medicine curriculum.

Background Polypropylene (PP) mesh is one of the most frequent materials used in hernia repair. We have experimentally evaluated the shrinkage of PP mesh depending on the place of implantation. Methods In 15 New Zealand rabbits a muscular defect measuring 3 × 3 cm was created in both pararectal sides of the abdominal wall. The defect was repaired using a PP mesh measuring 5 × 3.5 cm that was placed in the right side in the sublay location and in the left side in the onlay location. Five animals were killed on the 30th, 60th, and 90th postoperative days. Macroscopic measurement and microscopic study of the prosthesis–host tissue interfaces were performed. Results One rabbit was killed because of severe infection in the onlay mesh. Another 2 infections were tolerated in the onlay mesh side. All the prostheses were integrated in the host tissue at death. In the macroscopic evaluation the mesh areas were reduced by 25.92% on the 30th day, by 28.67% on the 60th day, and by 29.02% on the 90th day. The mesh shrinkage was greater in the onlay group than in the sublay group at the 3 time intervals. More inflammatory leukocyte and mononuclear responses also were seen in the onlay group. Conclusions These observations support the theory of PP mesh shrinkage as a consequence of the incorporation of the biomaterial to the scarring tissue. This shrinkage is significantly more intense if the meshes are placed in the onlay position.

The zinc finger transcription factor GATA4 controls specification and differentiation of multiple cell types during embryonic development. In mouse embryonic liver, Gata4 is expressed in the endodermal hepatic bud and in the adjacent mesenchyme of the septum transversum. Previous studies have shown that Gata4 inactivation impairs liver formation. However, whether these defects are caused by loss of Gata4 in the hepatic endoderm or in the septum transversum mesenchyme remains to be determined. In this study, we have investigated the role of mesenchymal GATA4 activity in liver formation. We have conditionally inactivated Gata4 in the septum transversum mesenchyme and its derivatives by using Cre/loxP technology. We have generated a mouse transgenic Cre line, in which expression of Cre recombinase is controlled by a previously identified distal Gata4 enhancer. Conditional inactivation of Gata4 in hepatic mesenchymal cells led to embryonic lethality around mouse embryonic stage 13.5, likely as a consequence of fetal anemia. Gata4 knockout fetal livers exhibited reduced size, advanced fibrosis, accumulation of extracellular matrix components and hepatic stellate cell (HSC) activation. Haploinsufficiency of Gata4 accelerated CCl4-induced liver fibrosis in adult mice. Moreover, Gata4 expression was dramatically reduced in advanced hepatic fibrosis and cirrhosis in humans. Conclusions: Our data demonstrate that mesenchymal GATA4 activity regulates HSC activation and inhibits the liver fibrogenic process. © 2014 by the American Association for the Study of Liver Diseases., I.D. was supported by a contract from Consejería de Salud, Junta de Andalucía (PI-0008). M.C. is a recipient of a predoctoral fellowship from Spanish Minis-try of Education (AP2009-2582). E.C. is a recipient of a MINECO fellowship (BES-2009-014847). This work was supported by grants from ISCIII cofunded byFondos FEDER, PI11/01125 to A.R., BFU2011-25304 (Ministerio de Economía y Competitividad), P11-CTS-7564 (Junta de Andalucía), and RD12/0019/0022 (TerCel network, ISCIII) to R.M.Ch., the Spanish Ministry of Science and Innovation (SAF2008-02469 and SAF2011-26805) and the AndalusianRegional Ministry of Economy, Science and Innovation (P08-CVI-3727) to D.A.C., and Instituto de Salud Carlos III (cofunded by FEDER: Red TerCel grantsRD06/0010/0025 and PI10/00964), Consejeríıa de Innovación Ciencia y Empresa, Junta de Andalucía (grant CTS-6505), the Ministry of Health and ConsumerAffairs (Advanced Therapies Program Grant TRA-120), and the European Union: BIOREG SOE3/P1/E750 (cofunded by FEDER) to B.S.

We evaluate the 5-year results of a single-centre prospective randomized trial that compared cyclosporine microemulsion (CyA-me) in triple therapy (plus steroids and azathioprine) and Tacrolimus (Tac) in double therapy (plus steroids) for primary immunosuppression. One hundred adult patients undergoing liver transplantation were randomized to receive Tac (n=51) or CyA-me (n=49). Ten patients in group A, and thirty-one patients in group B had their main immunosuppressive agent switched. The switch was much more frequent from CyA-me to Tac (n=31; 62.3%), mainly because of lack of efficacy (n=12; 38.7%). Six of 10 patients were shifted from Tac to CyA-me for side effects. The clinical course of the majority of patients converted from CyA-me to Tac improved clearly after conversion. Donor age and acute rejection (number, severity and rejection free days) had a significative association with lack of efficacy in group B. In these series, the conversion to Tac from CyA-me could be accomplished safely, with an excellent long-term outcome.

We report five patients who underwent laparotomy for liver metastasis from breast cancer without extrahepatic spread, with the intention to perform liver resection. All these patients had been subjected to modified radical mastectomy following systemic chemotherapy and periodical consecutive investigations to detect distant spreading. After laparotomy, patients have been regularly followed. Case 1, right trisegmentectomy in a 53-year-old woman, 36.5 months after the mastectomy. In the 17th postoperative month she continues without relapse. Case 2, hepatic artery ligature in a 41-year-old woman, 15 months after the mastectomy. In the 17th postoperative month she died. Case 3, bisegmentectomy (VI-VII) in a 51-year-old woman, 24 months after the mastectomy. In the 17th postoperative month she died. Case 4, exploratory laparotomy in a 51-year-old woman, 91 months after the mastectomy. In the 31th postoperative month she remains alive. Case 5, segmentectomy (IV) in a 59-year-old woman, 112 months after the mastectomy. In the 33th postoperative month she continues without relapse. As a conclusion, the surgical resection of liver metastasis from breast tumors after chemotherapy must be used in selected cases.