Análisis de la morbi-mortalidad a largo plazo en trasplante hepático

Consultable des del TDXTítol obtingut de la portada digitalitzadaAIMS. To retrospectively review our liver transplant performance to identify factors that influenced late mortality and morbidity. METHODS. Clinical records from 279 patients with liver transplants performed in Hospital Vall d'Hebron between January 1991and December 2001 and one year of survival, were reviewed. Minimal outcome was two years (r:1yr-12yr). Medium outcome was 9 years. The data evaluated by univariate and multivariate analyses regarding clinical outcome. RESULTS. Recipients mean was 55±5years, with 11%>65 years and 65% was male. Main indication for transplantation was postnecrotic cirrhosis (60%), followed by CHC in addition to cirrhosis (28%), choleostatic cirrhosis (6%), fulminant hepatitis (2%), Budd-Chiari (1%) and metabolic cirrhosis (1%). Half of the recipients (54%) were infected by HCV. A great percentage of recipients (44%) were at Child-Pugh C stage. Concomitant diseases were: renal insufficiency in 11%, arterial hypertension in 9%, diabetes mellitus in 16% and portal thrombosis in 18%. Inmunosupression at last the first year of liver transplantation was with cyclosporina in 108 patients (39%) and tacrolimus in 169 patients (60%). Patient actuarial survival what live at least a year, was 94%, 89%, 79% and 60% at 2yr, 3yr, 5yr and 10yr respectively. Seventy-five patients died in the outcome. Causes of death were recurrence primary disease in 11%, medical complications in 7% and de novo tumors in 5%. Rate of retransplant was 10% (27 patients). From all the pre-operative variables that appeared significant in univariate analysis, the factors that showed independent predictive value of late mortality were: old recipient (OR 1,03) , renal disfunction in the first year postransplant (OR 2,1) and liver disfunction at last the first year postransplant (OR 2,2). Characteristics of the patients with the risk factor of mortality «renal disfunction», were: >60 years, renal disfunction pretransplant or in the first year postransplant and Cyclosporine in the induction. Characteristics of the patients with the risk factor of mortality «liver disfunction», were: HCV pretransplant, HCV recurrence in the first year, acute rejection in the first year and Cyclosporine in the induction. The mean long term complications in liver transplant were: arterial hypertension in 50%, renal disfunction in 49%, diabetes mellitus in 30%, hypercholesterolaemia in 19%, hypertriglyceridaemia in 18%, cardiovascular complications in 15% and de novo tumors in 14%. From all the preoperative variables that appeared significant in univariate analysis, the factors that showed independent predictive value of late morbidity were: 1. Renal disfunction: old recipient, pretransplant cardiovascular complications and long stay in the hospital of the recipient. 2. Arterial hypertension: pretransplant arterial hypertension and CHC pretransplant in the recipient, donor exitus by traffic accident. 3. Diabetes Mellitus: pretransplant diabetes and HCV pretransplant in the recipient 4. Hypercholesterolaemia: no risk factors. Tacrolimus in the first year postransplantation is protector factor. 5. Hypertriglyceridaemia: cold ischaemia time>8h, donor male, intraoperative transfusion of platelets, long stay in ICU of the recipient. 6. Cardiovascular complications: old recipient and pretransplant cardiovascular complications, long time since of transplantation. 7. De novo tumors: old recipient. CONCLUSIONS. Old recipient, renal disfunction in the first year and liver disfunction at last the first year postTH are the most significant risk factor for late mortality. Arterial hypertension, renal disfunction and diabetes mellitus are the mean long term complications in liver transplantation, and the most significance risk factors are old recipient, HCV preTH, arterial hypertension and diabetes mellitus preTH, young donor and use Cyclosporine in the inmunosupression

Liver Transplantation for perihilar cholangiocarcinoma. Do we need to move forward?

Perihilar cholangiocarcinoma; Liver transplantation; OutcomesColangiocarcinoma perihilar; Trasplantament hepàtic; ResultatsColangiocarcinoma perihiliar; Trasplante hepático; ResultadosPerihilar cholangiocarcinoma (pCCA) is a challenging disease with limited options. Surgical resection and adjuvant therapy remain the only established treatment for those with resectable disease. Since the publication of the Mayo protocol in 2000, neoadjuvant chemoradiation and liver transplantation have become the standard of care in selected patients with unresectable de novo pCCA or resectable pCCA arising under primary sclerosing cholangitis. However, its application is diverse worldwide, and the need for donor organs is one of the main limitations. Also, differences in the neoadjuvant regimen used were observed. In this review, we discuss the latest results of this approach, the recommended tools for diagnostic work-up, and advances in systemic therapy to improve patient selection and long-term survival

Anàlisi del pacient trasplantat hepàtic després de 20 anys de supervivència

Hi ha nombrosos estudis de supervivència a curt i mig termini post-trasplantament hepàtic, però molt pocs que analitzin el seguiment a llarg termini. Aquest treball analitza l'estat del pacient i la funció de l'empelt després de 20 anys de supervivència post-trasplantament hepàtic, les principals causes de mortalitat i factors de risc. Els resultats mostren una supervivència del 21%, així com l'efecte nociu a llarg termini de la utilització de la immunosupressió pel que fa a morbiditat i mortalitat.Hay numerosos estudios de supervivencia a corto y medio plazo post- trasplante hepático, pero muy pocos que analicen el seguimiento a largo plazo. Este trabajo analiza el estado del paciente y la función del injerto tras 20 años de supervivencia post-trasplante hepático, las principales causas de mortalidad y factores de riesgo. Los resultados muestran una supervivencia del 21%, así como el efecto nocivo a largo plazo de la utilización de la inmunosupresión en lo que respecta a morbilidad y mortalidad

Pancreatic cancer

Cáncer de páncreasCàncer de pàncreesPancreatic cancerThe need for a common education and training track in surgical oncology across Europe has been emphasized. ESSO provides several hands-on courses for skills training and face-to-face discussions. The core curriculum provides a framework for the overall theoretical requirements in surgical oncology. The UEMS/EBSQ fellowship exam is designed to test core competencies in the candidate's core knowledge in their prespecified area of expertise. A core set of points for each cancer type is lacking. Hence, a condensed outline of themed expected to be covered in the curriculum and relevant to an optimal practice in surgical oncology is provided. This article outlines pancreatic cancer

Early peroxisome proliferator-activated receptor gamma regulated genes involved in expansion of pancreatic beta cell mass.

BACKGROUND: The progression towards type 2 diabetes depends on the allostatic response of pancreatic beta cells to synthesise and secrete enough insulin to compensate for insulin resistance. The endocrine pancreas is a plastic tissue able to expand or regress in response to the requirements imposed by physiological and pathophysiological states associated to insulin resistance such as pregnancy, obesity or ageing, but the mechanisms mediating beta cell mass expansion in these scenarios are not well defined. We have recently shown that ob/ob mice with genetic ablation of PPARγ2, a mouse model known as the POKO mouse failed to expand its beta cell mass. This phenotype contrasted with the appropriate expansion of the beta cell mass observed in their obese littermate ob/ob mice. Thus, comparison of these models islets particularly at early ages could provide some new insights on early PPARγ dependent transcriptional responses involved in the process of beta cell mass expansion RESULTS: Here we have investigated PPARγ dependent transcriptional responses occurring during the early stages of beta cell adaptation to insulin resistance in wild type, ob/ob, PPARγ2 KO and POKO mice. We have identified genes known to regulate both the rate of proliferation and the survival signals of beta cells. Moreover we have also identified new pathways induced in ob/ob islets that remained unchanged in POKO islets, suggesting an important role for PPARγ in maintenance/activation of mechanisms essential for the continued function of the beta cell. CONCLUSIONS: Our data suggest that the expansion of beta cell mass observed in ob/ob islets is associated with the activation of an immune response that fails to occur in POKO islets. We have also indentified other PPARγ dependent differentially regulated pathways including cholesterol biosynthesis, apoptosis through TGF-β signaling and decreased oxidative phosphorylation.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

The ESSO core curriculum committee update on surgical oncology

Cancer care; Curriculum; Surgical oncologyCuidado del cancer; Plan de estudios; Oncología quirúrgicaCura del càncer; Pla d'estudis; Oncologia quirúrgicaIntroduction Surgical oncology is a defined specialty within the European Board of Surgery within the European Union of Medical Specialists (UEMS). Variation in training and specialization still occurs across Europe. There is a need to align the core knowledge needed to fulfil the criteria across subspecialities in surgical oncology. Material and methods The core curriculum, established in 2013, was developed with contributions from expert advisors from within the European Society of Surgical Oncology (ESSO), European Society for Radiotherapy and Oncology (ESTRO) and European Society of Medical Oncology (ESMO) and related subspeciality experts. Results The current version reiterates and updates the core curriculum structure needed for current and future candidates who plans to train for and eventually sit the European fellowship exam for the European Board of Surgery in Surgical Oncology. The content included is not intended to be exhaustive but, rather to give the candidate an idea of expectations and areas for in depth study, in addition to the practical requirements. The five elements included are: Basic principles of oncology; Disease site specific oncology; Generic clinical skills; Training recommendations, and, lastly; Eligibility for the EBSQ exam in Surgical Oncology. Conclusions As evidence-based care for cancer patients evolves through research into basic science, translational research and clinical trials, the core curriculum will evolve, mature and adapt to deliver continual improvements in cancer outcomes for patients

Liver transplantation in metastatic colorectal cancer: are we ready for it?

Liver transplantation; Metastatic colorectal cancerTrasplantament de fetge; Càncer colorectal metastàticTrasplante de hígado; Cáncer colorrectal metastásicoColorectal cancer (CRC) is a prevalent disease worldwide, with more than 50% of patients developing metastases to the liver. Five-year overall survival remains modest among patients with metastatic CRC (mCRC) treated with conventional therapies however, liver transplantation in a highly selected population can improve clinical outcomes with an impressive 5-year overall survival of 83%. Despite liver transplantation appearing to be a promising therapeutical option for well-selected patients with mCRC with the liver-limited disease, these data come from small monocentric trials which included a heterogeneous population. Currently, several clinical trials are evaluating liver transplantation in this scenario, aiming for a more accurate patient selection by integrating liquid biopsy, tissue profiling, and nuclear medicine to the already known clinical biomarkers that eventually may lead to a survival improvement. In this paper, the clinical outcomes and inclusion criteria from the most relevant clinical trials and clinical series involving liver transplantation in patients with liver-limited disease colorectal cancer are reviewed as well as the trials currently recruiting

Impact of Preoperative Chemotherapy Features on Patient Outcomes after Hepatectomy for Initially Unresectable Colorectal Cancer Liver Metastases: A LiverMetSurvey Analysis

Liver metastases; Liver resection; Preoperative chemotherapyMetástasis hepáticas; Resección hepática; Quimioterapia preoperatoriaMetàstasis hepàtiques; Resecció hepàtica; Quimioteràpia preoperatòriaBackground: Prognostic factors have been extensively reported after resection of colorectal liver metastases (CLM); however, specific analyses of the impact of preoperative systemic anticancer therapy (PO-SACT) features on outcomes is lacking. Methods: For this real-world evidence study, we used prospectively collected data within the international surgical LiverMetSurvey database from all patients with initially-irresectable CLM. The main outcome was Overall Survival (OS) after surgery. Disease-free (DFS) and hepatic-specific relapse-free survival (HS-RFS) were secondary outcomes. PO-SACT features included duration (cumulative number of cycles), choice of the cytotoxic backbone (oxaliplatin- or irinotecan-based), fluoropyrimidine (infusional or oral) and addition or not of targeted monoclonal antibodies (anti-EGFR or anti-VEGF). Results: A total of 2793 patients in the database had received PO-SACT for initially irresectable diseases. Short (<7 or <13 cycles in 1st or 2nd line) PO-SACT duration was independently associated with longer OS (HR: 0.85 p = 0.046), DFS (HR: 0.81; p = 0.016) and HS-RFS (HR: 0.80; p = 0.05). All other PO-SACT features yielded basically comparable results. Conclusions: In this international cohort, provided that PO-SACT allowed conversion to resectability in initially irresectable CLM, surgery performed as soon as technically feasible resulted in the best outcomes. When resection was achieved, our findings indicate that the choice of PO-SACT regimen had a marginal if any, impact on outcomes

Epigenetic Modifications in the Biology of Nonalcoholic Fatty Liver Disease: The Role of DNA-Hydroxymethylation and TET Proteins

The 5-Hydroxymethylcytosine (5-hmC) is an epigenetic modification whose role in the pathogenesis of metabolic-related complex diseases remains unexplored; 5-hmC appears to be prevalent in the mitochondrial genome. The Ten-Eleven-Translocation (TET) family of proteins is responsible for catalyzing the conversion of 5-methylcytosine to 5-hmC. We hypothesized that epigenetic editing by 5-hmC might be a novel mechanism through which nonalcoholic fatty liver disease (NAFLD)-associated molecular traits could be explained. Hence, we performed an observational study to explore global levels of 5-hmC in fresh liver samples of patients with NAFLD and controls (n = 90) using an enzyme-linked-immunosorbent serologic assay and immunohistochemistry. We also screened for genetic variation in TET 1–3 loci by next generation sequencing to explore its contribution to the disease biology. The study was conducted in 2 stages (discovery and replication) and included 476 participants. We observed that the amount of 5-hmC in the liver of both NAFLD patients and controls was relatively low (up to 0.1%); a significant association was found with liver mitochondrial DNA copy number (R = 0.50, P = 0.000382) and PPARGC1A-mRNA levels (R = −0.57, P = 0.04). We did not observe any significant difference in the 5-hmC nuclear immunostaining score between NAFLD patients and controls; nevertheless, we found that patients with NAFLD (0.4 ± 0.5) had significantly lower nonnuclear-5-hmC staining compared with controls (1.8 ± 0.8), means ± standard deviation, P = 0.028. The missense p.Ile1123Met variant (TET1-rs3998860) was significantly associated with serum levels of caspase-generated CK-18 fragment-cell death biomarker in the discovery and replication stage, and the disease severity (odds ratio: 1.47, 95% confidence interval: 1.10–1.97; P = 0.005). The p.Ile1762Val substitution (TET2-rs2454206) was associated with liver PPARGC1A-methylation and transcriptional levels, and Type 2 diabetes. Our results suggest that 5-hmC might be involved in the pathogenesis of NAFLD by regulating liver mitochondrial biogenesis and PPARGC1A expression. Genetic diversity at TET loci suggests an “epigenetic” regulation of programmed liver-cell death and a TET-mediated fine-tuning of the liver PPARGC1A-transcriptional program.Fil: Pirola, Carlos José. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: Scian, Romina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: Fernández Gianotti, Tomás. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: Dopazo, Hernán Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Ecología, Genética y Evolución de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Ecología, Genética y Evolución de Buenos Aires; ArgentinaFil: Rohr, Cristian Oscar. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Ecología, Genética y Evolución de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Ecología, Genética y Evolución de Buenos Aires; ArgentinaFil: San Martino, Julio. Provincia de Buenos Aires. Ministerio de Salud. Hospital Municipal Dr. Diego Thompson; ArgentinaFil: Castaño, Gustavo Osvaldo. Gobierno de la Ciudad de Buenos Aires. Hospital "Dr. Abel Zubizarreta"; ArgentinaFil: Sookoian, Silvia Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentin

Repaglinide Induces ATF6 Processing and Neuroprotection in Transgenic SOD1G93A Mice

The interaction of the activating transcription factor 6 (ATF6), a key effector of the unfolded protein response (UPR) in the endoplasmic reticulum, with the neuronal calcium sensor Downstream Regulatory Element Antagonist Modulator (DREAM) is a potential therapeutic target in neurodegeneration. Modulation of the ATF6&ndash;DREAM interaction with repaglinide (RP) induced neuroprotection in a model of Huntington&rsquo;s disease. Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder with no cure, characterized by the progressive loss of motoneurons resulting in muscle denervation, atrophy, paralysis, and death. The aim of this work was to investigate the potential therapeutic significance of DREAM as a target for intervention in ALS. We found that the expression of the DREAM protein was reduced in the spinal cord of SOD1G93A mice compared to wild-type littermates. RP treatment improved motor strength and reduced the expression of the ALS progression marker collagen type XIX&alpha;1 (Col19&alpha;1 mRNA) in the quadriceps muscle in SOD1G93A mice. Moreover, treated SOD1G93A mice showed reduced motoneuron loss and glial activation and increased ATF6 processing in the spinal cord. These results indicate that the modulation of the DREAM&ndash;ATF6 interaction ameliorates ALS symptoms in SOD1G93A mice