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Old patients with hepatotoxicity have been scarcely studied in idiosyncratic drug-induced liver injury (DILI) cohorts. We sought for the distinctive characteristics of DILI in older patients across age groups. A total of 882 DILI patients included in the Spanish DILI Registry (33% ≥65 years) were categorized according to age: “young” (

Alcohol-related liver disease (ARLD) is the most prevalent cause of advanced liver disease and liver cirrhosis in Europe, including Spain. According to the World Health Organization the fraction of liver cirrhosis attributable to alcohol use in Spain is 73.8% among men and 56.3% among women. ARLD includes various stages such as steatohepatitis, cirrhosis and hepatocellular cancer. In addition, patients with underlying ARLD and heavy alcohol intake may develop alcoholic hepatitis, which is associated with high mortality. To date, the only effective treatment to treat ARLD is prolonged withdrawal. There are no specific treatments, and the only treatment that increases life expectancy in alcoholic hepatitis is prednisolone. For patients with alcoholic hepatitis who do not respond to treatment, some centres offer the possibility of an early transplant. These clinical practice guidelines aim to propose recommendations on ARLD taking into account their relevance as a cause of advanced chronic liver disease and liver cirrhosis in our setting. This paper aims to answer the key questions for the clinical practice of Gastroenterology, Hepatology, as well as Internal Medicine and Primary Health Centres, making the most up-to-date information regarding the management and treatment of ARLD available to health professionals. These guidelines provide evidence-based recommendations for the clinical management of this disease.

[Background & Aims] Prospective drug-induced liver injury (DILI) registries are important sources of information on idiosyncratic DILI. We aimed to present a comprehensive analysis of 843 patients with DILI enrolled into the Spanish DILI Registry over a 20-year time period., [Methods] Cases were identified, diagnosed and followed prospectively. Clinical features, drug information and outcome data were collected., [Results] A total of 843 patients, with a mean age of 54 years (48% females), were enrolled up to 2018. Hepatocellular injury was associated with younger age (adjusted odds ratio [aOR] per year 0.983; 95% CI 0.974–0.991) and lower platelet count (aOR per unit 0.996; 95% CI 0.994–0.998). Anti-infectives were the most common causative drug class (40%). Liver-related mortality was more frequent in patients with hepatocellular damage aged ≥65 years (p = 0.0083) and in patients with underlying liver disease (p = 0.0221). Independent predictors of liver-related death/transplantation included nR-based hepatocellular injury, female sex, higher onset aspartate aminotransferase (AST) and bilirubin values. nR-based hepatocellular injury was not associated with 6-month overall mortality, for which comorbidity burden played a more important role. The prognostic capacity of Hy’s law varied between causative agents. Empirical therapy (corticosteroids, ursodeoxycholic acid and MARS) was prescribed to 20% of patients. Drug-induced autoimmune hepatitis patients (26 cases) were mainly females (62%) with hepatocellular damage (92%), who more frequently received immunosuppressive therapy (58%)., [Conclusions] AST elevation at onset is a strong predictor of poor outcome and should be routinely assessed in DILI evaluation. Mortality is higher in older patients with hepatocellular damage and patients with underlying hepatic conditions. The Spanish DILI Registry is a valuable tool in the identification of causative drugs, clinical signatures and prognostic risk factors in DILI and can aid physicians in DILI characterisation and management., [Lay summary] Clinical information on drug-induced liver injury (DILI) collected from enrolled patients in the Spanish DILI Registry can guide physicians in the decision-making process. We have found that older patients with hepatocellular type liver injury and patients with additional liver conditions are at a higher risk of mortality. The type of liver injury, patient sex and analytical values of aspartate aminotransferase and total bilirubin can also help predict clinical outcomes., The present study has been supported by grants of Instituto de Salud Carlos III cofounded by Fondo Europeo de Desarrollo Regional – FEDER (contract numbers: PI19/00883, PI16/01748, PI18/00901, PI18/01804, PI-0285-2016, PI-0274-2016, PI-0310-2018, PT17/0017/0020) and Agencia Española del Medicamento. CIBERehd and Plataforma ISCIII Ensayos Clinicos are funded by Instituto de Salud Carlos III. MRD holds a Joan Rodes (JR16/00015)/Acción B clinicos investigadores (B-0002-2019) and JSC a Rio Hortega (CM17/00243) research contract from ISCIII and Consejería de Salud de Andalucía.

Resumen El articulo recoge el conjunto de medidas propuestas por la SEPD, la AEEH, el GETECCU y la AEG que pretenden servir de ayuda a los servicios en su reincorporacion a la actividad habitual. Hemos confeccionado una serie de recomendaciones practicas respecto al manejo y a la reintroduccion progresiva de la actividad asistencial. Estas recomendaciones estan guiadas por la escasa y cambiante evidencia disponible y seran objeto de futuras actualizaciones en base a las necesidades diarias y a la disponibilidad del material fungible para adecuarse a ellas, y se podran implementar en cada servicio en funcion de la incidencia acumulada de SARS-CoV-2 en cada region y de la carga que la epidemia ha ocasionado en cada uno de los hospitales. Los objetivos generales de estas recomendaciones son: a) Proteger a nuestros pacientes de los riesgos de la infeccion por SARS-CoV-2 y prestarles una atencion de calidad. b) Proteger a todos los profesionales sanitarios de los riesgos de la infeccion por SARS-CoV-2. c) Recuperar el normal funcionamiento de nuestros servicios en un entorno de riesgo continuado de infeccion por SARS-CoV-2.

Scope Modulation of intestinal microbiota has emerged as a new therapeutic approach for non-alcoholic fatty liver disease (NAFLD). Herein, it is addressed whether gut microbiota modulation by quercetin and intestinal microbiota transplantation can influence NAFLD development. Methods and results Gut microbiota donor mice are selected according to their response to high-fat diet (HFD) and quercetin in terms of obesity and NAFLD-related biomarkers. Germ-free recipients displayed metabolic phenotypic differences derived from interactions between microbiota transplanted, diets, and quercetin. Based on the evaluation of hallmark characteristics of NAFLD, it is found that gut microbiota transplantation from the HFD-non-responder donor and the HFD-fed donor with the highest response to quercetin results in a protective phenotype against HFD-induced NAFLD, in a mechanism that involves gut-liver axis alteration blockage in these receivers. Gut microbiota from the HFD-responder donor predisposed transplanted germ-free mice to NAFLD. Divergent protective and deleterious metabolic phenotypes exhibited are related to definite microbial profiles in recipients, highlighting the predominant role of Akkermansia genus in the protection from obesity-associated NAFLD development. Conclusions The results provide scientific support for the prebiotic capacity of quercetin and the transfer of established metabolic profiles through gut microbiota transplantation as a protective strategy against the development of obesity-related NAFLD.

1 p. Dysbiosis and gut-liver axis alteration have been pointed as important contributors to obesity and non-alcoholic fatty liver disease (NAFLD) development. Modulation of intestinal microbiota (IM) emerge as a promising therapeutic strategy for obesity-associated NAFLD. This study aims to determine the effect of IM transplantation and quercetin supplementation in a high fat diet (HFD)-based NAFLD model in germ free mice (GFm). Resumen de un trabajo resultado del proyecto de investigación financiado por la Consejería de Educación de la Junta de Castilla y León (referencia LE063U16) SI

Background: The presence of a family history implies an increased risk for developing colorectal cancer (CRC), and may require a different screening strategy. The aim of this study was to evaluate lesions found during colonoscopies of patients that had a family history of CRC. Material and methods: A retrospective study was conducted that included consecutive colonoscopies performed on patients with a family history of CRC at a referral center within the period from April 2000 to January 2012. The colonoscopic findings were analyzed in relation to sex, age, and the presence or absence of symptoms. Results: Data from 3,792 colonoscopies were collected. The mean age of the patients was 53.14 years (SD 12.22), and 57.4% were women. Colonoscopy was normal in 71.7% of the cases, with hyperplastic polyps being detected in 7.1%, and adenomatous polyps in 19.8% (39.4% of them were high risk). There was a 1.5% presence of adenocarcinomas in the subjects. Polyps and CRC were predominant in men (P=.001 and P=.027, respectively) and there was a linear increase with age. Symptomatic patients had a higher CRC detection rate (P

Molecular mechanisms contributing to hepatitis C virus (HCV)-associated steatosis are not well established, although HCV gene expression has been shown to alter host cell cholesterol/lipid metabolism. As liver X receptors (LXRs) play a role as key modulators of metabolism signaling in the development of steatosis, we aimed to investigate in an HCV in vitro model the effect of HCV NS5A protein, core protein, and viral replication on the intracellular lipid accumulation and the LXRα-regulated expression of lipogenic genes. The effects of LXRα siRNA or agonist GW3965 treatment on lipogenesis and HCV replication capacity in our HCV replicon system were also examined. NS5A- and core-expressing cells and replicon-containing cells exhibited an increase of lipid accumulation by inducing the gene expression and the transcriptional activity of LXRα, and leading to an increased expression of its lipogenic target genes sterol regulatory element binding protein-1c, peroxisome proliferator-activated receptor-γ, and fatty acid synthase. Transcriptional induction by NS5A protein, core protein, and viral replication occurred via LXR response element activation in the lipogenic gene promoter. No physical association between HCV proteins and LXRα was observed, whereas NS5A and core proteins indirectly upregulated LXRα through the phosphatidylinositol 3-kinase pathway. Finally, it was found that LXRα knockdown or agonist-mediated LXRα induction directly regulated HCV-induced lipogenesis and HCV replication efficiency in replicon-containing cells. Combined, our data suggest that LXRα-mediated regulation of lipogenesis by core and NS5A proteins may contribute to HCV-induced liver steatosis and to the efficient replication of HCV.

Objetivo Analizar las caracteristicas de los pacientes con neoplasias vesicales que desarrollaron una neoplasia primaria maligna multiple (NPMM) en el area sanitaria de Leon, el impacto sobre la supervivencia y las posibles variables pronosticas. Material y metodos Utilizando los datos del Registro de Tumores del Hospital de Leon se han seleccionado aquellos pacientes con tumors vesicales diagnosticados entre 1993 y 2002, clasificandolos en dos grupos: el primero formado por 71 pacientes diagnosticados de NPMM y el segundo con 159 pacientes con tumores unicos diagnosticados entre 1996 y 1997. Resultados La incidencia de NPMM fue del 7,1%. Mas de la mitad de los pacientes tenian antecedents familiares oncologicos. Las segundas neoplasias mas frecuentes fueron las urologicas, seguidas de la digestivas y respiratorias. La supervivencia de los pacientes con NPMM fue un 21% inferior a la de los pacientes con tumores unicos. Las variables que influyeron en el pronostico fueron el estadio de la segunda neoplasia, el padecimiento de una segunda neoplasia urologica y la aplicacion de tratamiento quirurgico en el segundo tumor. Conclusiones Las NPMM en pacientes con tumores vesicales son frecuentes en nuestro medio. La elevada frecuencia de antecedents familiares oncologicos en estos pacientes sugiere la existencia de una posible base genetica. El pronostico de los pacientes con NPMM es peor al de los pacientes con neoplasias unicas, aunque no se observan diferencias en cuanto al pronostico de los pacientes con NPMM sincronicas y metacronicas.

The presence of a family history implies an increased risk for developing colorectal cancer (CRC), and may require a different screening strategy. The aim of this study was to evaluate lesions found during colonoscopies of patients that had a family history of CRC.A retrospective study was conducted that included consecutive colonoscopies performed on patients with a family history of CRC at a referral center within the period from April 2000 to January 2012. The colonoscopic findings were analyzed in relation to sex, age, and the presence or absence of symptoms.Data from 3,792 colonoscopies were collected. The mean age of the patients was 53.14 years (SD 12.22), and 57.4% were women. Colonoscopy was normal in 71.7% of the cases, with hyperplastic polyps being detected in 7.1%, and adenomatous polyps in 19.8% (39.4% of them were high risk). There was a 1.5% presence of adenocarcinomas in the subjects. Polyps and CRC were predominant in men (P=.001 and P=.027, respectively) and there was a linear increase with age. Symptomatic patients had a higher CRC detection rate (P.001), but no differences were observed in relation to polyp diagnosis.Age and male sex increased the risk for presenting with CRC or adenomas in the group of patients with a family history of CRC, and the presence of symptoms was associated with a greater risk for presenting with CRC.

Resumen Objetivo La esfinterotomia de aguja es una tecnica empleada para conseguir el acceso a la via biliar, cuando los metodos de canulacion habituales han fallado. El objetivo ha sido analizar los resultados de la realizacion de la esfinterotomia de aguja en pacientes con inaccesibilidad a la via biliar (canulacion dificil) mediante tecnicas estandar en colangiopancreatografia retrograda endoscopica, y los factores asociados con el exito y complicaciones. Material y metodos Estudio prospectivo que incluye a 72 pacientes entre enero de 1998 y diciembre de 2004, sometidos a esfinterotomia de aguja por canulacion dificil de la via biliar por el mismo endoscopista (J.E.). Los resultados se analizaron respecto al exito en acceder a la via biliar, su consecucion en una o mas sesiones, su posible relacion con la enfermedad de base y la incidencia y gravedad de las complicaciones. Resultados Se realizaron 72 esfinterotomias de aguja de un total de 1.062 esfinterotomias (6,7%). En el 77,7% de los pacientes se coloco previamente una protesis pancreatica. El diagnostico final fue: coledocolitiasis en el 31,9%; cancer de pancreas en el 16,6%; colangiocarcinoma en el 13,8%; estenosis benigna en el 8,3%; disfuncion del esfinter de Oddi en el 6,9%; normal en el 6,9%, y miscelanea en el 13,8%. Se obtuvo exito en la canulacion en el 87,5% (63/72), y se consiguio en la primera sesion en el 73% (46/63). Se logro el acceso biliar en el 72,7% de los casos (16/22) de neoplasia biliopancreatica, frente al 94% (47/50) en pacientes con otros diagnosticos (p = 0,03). Once pacientes (15,2%) presentaron 12 complicaciones (16,6%) (6 pancreatitis, 4 colangitis, 1 hemorragia papilar y 1 relleno de la vena porta). El uso de protesis pancreatica se relaciono con un porcentaje mayor de exito y menor de complicaciones, alcanzando significacion estadistica en esta ultima (p = 0,03). Conclusiones La esfinterotomia de aguja con protesis pancreatica puede ser un procedimiento seguro en pacientes con canulacion dificil de la via biliar. La presencia de neoplasia biliopancreatica es un factor de riesgo de no consecucion del acceso biliar frente a otros diagnosticos. La incidencia de complicaciones esta en consonancia con otros estudios, y no se han hallado pancreatitis graves ni perforaciones.

Objetivo : Analizar prospectivamente los resultados obtenidos mediante dilatacion neumatica papilar (DNP) en el tratamiento de coledocolitiasis, en pacientes con riesgo de complicaciones si se realizara esfinterotomia endoscopica (EE). Pacientes Y Metodo : Se incluyen 33 pacientes entre enero de 2001 y junio de 2003 (edad media 76,2 anos). Los criterios de DNP fueron: coledocolitiasis ≤ 10 mm en pacientes con diverticulos peripapilares, alteraciones hemostaticas, Billroth II o preservacion del esfinter de Oddi. La sedacion se realizo por anestesista en el 79% de los pacientes. La DNP se efectuo con un cateter balon dilatador de 8 o 10 mm de diametro, durante 2 min. Se valoro la eficacia, la duracion del procedimiento, las complicaciones al dia 30 y el grado de satisfaccion de los pacientes. Resultados : Se consiguio la extraccion de los calculos en todos ellos (100%). La duracion media fue de 26 min. Dos pacientes presentaron pancreatitis leve (6%). Hubo elevacion de la amilasa serica en 16 pacientes (48%): ≥ 3 veces (hiperamilasemia post-DNP) en 11 (33%). La prueba fue nada molesta en 25/26 (96%) pacientes sedados por anestesista frente a 2/5 (40%) sedados por endoscopista. Conclusiones : La DNP es una opcion terapeutica eficaz y sencilla en el tratamiento de coledocolitiasis de pequeno tamano (. 10 mm), en situaciones especiales de riesgo. La duracion de la colangiopancreatografia retrograda endoscopica (CPRE) no supone un tiempo prolongado. Las complicaciones son infrecuentes (6%) y leves. La hiperamilasemia post-DNP es frecuente y generalmente sin trascendencia clinica. La sedacion por un anestesista mejora la satisfaccion del paciente.

1 p. Gut microbiota is involved in obesity, metabolic syndrome and nonalcoholic fatty liver disease (NAFLD). Quercetin may have the ability to modulate the intestinal microbiota composition, suggesting therapeutic potential in NAFLD. The present study aims to investigate the beneficial effect of quercetin treatment on dysbiosis, intestinal barrier dysfunction and gut-liver axis alteration in high-fat diet (HFD)-fed mice. Resumen de un trabajo resultado del proyecto de investigación financiado por la Consejería de Educación de la Junta de Castilla y León (referencia LE063U16) SI

Objetivo Conocer el grado de asociacion entre los valores sericos de alfa-1-antitripsina y los diferentes genotipos de esta asi como su expresion clinica. Pacientes Y Metodos Se determino el genotipo de la alfa-1- antitripsina mediante reaccion en cadena de la polimerasa (PCR) seguido de corte con enzimas de restriccion en 212 pacientes en los que se habia solicitado la determinacion de alfa-1-antitripsina serica. Se han analizado las causas por las que se solicitaron, la existencia de enfermedad pulmonar o hepatica, los diagnosticos clinicos y la repercusion funcional. Resultados Se evaluaron 212 pacientes, el 68% varones, con una edad media de 34 ± 20 anos. En 23 casos (10,8%) existia una variante deficiente (faltaban uno o dos alelos M) y en 8 pacientes (3,8%) el genotipo fue ZZ. Todos los pacientes con genotipo MM tenian unos valores de alfa-1-antitripsina de 75 mg/dl o superior mientras que ninguno con genotipo ZZ tenia mas de 40 mg/dl. Todos los pacientes con genotipo ZZ tenian alteraciones: tres enfisema pulmonar, uno enfermedad pulmonar obstructiva cronica (EPOC) y cuatro hipertransaminasemia. Un paciente con enfisema pulmonar tenia insuficiencia ventilatoria grave, mientras que en el resto de los pacientes con problemas respiratorios la insuficiencia ventilatoria fue leve o moderada. Ningun paciente con hipertransaminasemia tenia signos ecograficos de hipertension portal o datos clinicos o analiticos de reduccion de la funcion hepatica. Conclusiones Existe una asociacion estrecha entre los valores de alfa-1-antitripsina y los diferentes genotipos, por lo que, en condiciones basales, con valores sericos de alfa-1-antitripsina superiores a 75 mg/dl, no es necesario realizar genotipo. La repercusion funcional de las variantes deficientes en adultos jovenes es poco marcada.

Objetivo Conocer la situacion actual de la colangiopancreatografia retrogada endoscopica (CPRE) y la repercusion que la introduccion de la colangiorresonancia magnetica (CRM) ha tenido sobre esta. Evaluar el rendimiento diagnostico de la CRM desde su inicio en la patologia biliar obstructiva. Material Y Metodos Analisis retrospectivo de las CPRE realizadas desde enero de 1998 a diciembre de 2000, y las CRM realizadas por sospecha de enfermedad biliar obstructiva desde mayo de 1999 hasta diciembre de 2000. Cuando se realizaron ambas tecnicas, se evaluo el rendimiento diagnostico de la CRM. Resultados Se realizaron 927 CPRE (45,3% varones), con una edad media ± desviacion estandar de 69,2 ± 14,6 anos. Se realizo terapeutica en 688 ocasiones (77%), fundamentalmente esfinterotomia (69,9%) y colocacion de protesis de polietileno (21,8%) y autoexpandibles (9,9%). El numero de CPRE por ano fue de 261, 330 y 336 en 1998, 1999 y 2000, respectivamente, de las que un 76,6, un 80 y un 76,9% fueron CPRE con actuacion terapeutica. La CRM se practico en 63 pacientes por sospecha de enfermedad biliar. La CRM no fue seguida de CPRE en 27 de 59 (45,8%) pacientes, siendo suficiente para el diagnostico y evitando la realizacion de una CPRE. En los 35 pacientes a quienes realizaron ambas tecnicas (CRM y CPRE), el rendimiento diagnostico de la CRM frente a la CPRE fue: sensibilidad del 100%, especificidad del 50%, valor predictivo positivo del 87,1%, valor predictivo negativo del 100% y valor global del 89%. Se analizaron los casos responsables de la baja especificidad (todos por coledocolitiasis) y se encontro un desfase de tiempo importante entre la realizacion de CRM y de CPRE (limites, 7-35 dias) en el que probablemente se soluciono la coledocolitiasis de forma espontanea. Conclusiones a) En contra de lo que cabria esperar, el numero total de CPRE parece aumentar, con un elevado porcentaje de terapeutica endoscopica; b) la elevada sensibilidad diagnostica de la CRM hace que sea la tecnica ideal para evitar la CPRE diagnostica y permitir asi un mayor desarrollo de la vertiente terapeutica de la CPRE.

Background: Physiological effects caused by abdominal insufflation in the course of laparoscopic surgery are partially unknown. The purpose of the present study was to determine if indocyanine green (ICG) pharmacokinetic parameters, as an index of hepatic blood flow, change during laparoscopic surgery in the presence of a CO2 pneumoperitoneum. This effect could cause important alterations in the kinetics of anesthetic drugs. Methods: Eighteen female pigs were anaesthetized under constant ventilation and randomly assigned to three groups undergoing insufflation with CO2 (I), laparoscopic oophorectomy with CO2 pneumoperitoneum (LS), or oophorectomy by open surgery (OS). CO2 pneumoperitoneum was performed at 14 mmHg. ICG (1 mg/kg) was injected into a marginal vein on two separate occasions: 30 min before and 30 min after the start of insufflation or surgery. Blood was sampled from the carotid artery at time intervals after the injection of ICG and after pharmacokinetic parameters were obtained by a computer program. Results: The area under the curve (AUC0–∞) indicated important disfunctions in ICG availability in all three groups of animals, with significant increases of 104%, 82%, and 48% for groups I, LS, and OS, respectively. The ICG apparent half-life did not significantly change in group OS, but it rose in groups I (+17%) and LS (+28%). ICG clearance was significantly reduced by 32% in group OS and to a larger extent in groups I and LS (−45% and −46%, respectively). Conclusion: These findings confirm the contribution of CO2 pneumoperitoneum to decreased liver blood flow during laparoscopic surgery.

A technique of immediate breast reconstruction, combining skin sparing mastectomy and autologous latissimus breast reconstruction, is presented. In this study, 50 patients underwent this procedure between May 1993 and May 1997. The most frequent indication (62%) was ductal carcinoma in situ (multifocal, high grade or larger than 3 cm). In 38% of cases, the patients had a contraindication to the TRAM flap; in the other cases (62%) the patients preferred the dorsal donor site to the abdominal site. Reduction of the contralateral breast was done in 20% of cases of unilateral reconstruction. The aesthetic results, evaluated by two others surgeons, were rated as very good in 88% of cases, good in 8% and poor in 4%. Study of patient satisfaction showed 84% of patients to be pleased, 12% satisfied and 4% poorly satisfied. Dorsal sequelae were rated as slight in 96% of cases, intermediate in 4% and marked in none. The main disadvantage was dorsal seroma which occurred in 62% of cases but was easily managed by repeated aspiration. No patient developed a local recurrence or distant metastases. This technique represents a significant advance in breast reconstruction, giving a breast of natural shape and consistency with no transverse scar or patch effect due to the flap.

There is experimental evidence that some antioxidant flavonoids show therapeutic potential in the treatment of hepatitis C through inhibition of hepatitis C virus (HCV) replication. We examined the effect of treatment with the flavonols quercetin and kaempferol, the flavanone taxifolin and the flavone apigenin on HCV replication efficiency in an in vitro model. While all flavonoids studied were able to reduce viral replication at very low concentrations (ranging from 0.1 to 5 μM), quercetin appeared to be the most effective inhibitor of HCV replication, showing a marked anti-HCV activity in replicon-containing cells when combined with interferon (IFN)α. The contribution of oxidative/nitrosative stress and lipogenesis modulation to inhibition of HCV replication by quercetin was also examined. As expected, quercetin decreased HCV-induced reactive oxygen and nitrogen species (ROS/RNS) generation and lipoperoxidation in replicating cells. Quercetin also inhibited liver X receptor (LXR)α-induced lipid accumulation in LXRα-overexpressing and replicon-containing Huh7 cells. The mechanism underlying the LXRα-dependent lipogenesis modulatory effect of quercetin in HCV-replicating cells seems to involve phosphatidylinositol 3-kinase (PI3K)/AKT pathway inactivation. Thus, inhibition of the PI3K pathway by LY294002 attenuated LXRα upregulation and HCV replication mediated by lipid accumulation, showing an additive effect when combined with quercetin. Inactivation of the PI3K pathway by quercetin may contribute to the repression of LXRα-dependent lipogenesis and to the inhibition of viral replication induced by the flavonol. Combined, our data suggest that oxidative/nitrosative stress blockage and subsequent modulation of PI3K-LXRα-mediated lipogenesis might contribute to the inhibitory effect of quercetin on HCV replication.

The purpose of this study was to investigate whether antipyrine estimation in saliva provides valid information on plasma antipyrine clearance (APCl) and can be useful as an index of changes in drug metabolism with age. Antipyrine kinetics was studied in 93 elderly (mean age 82 years) and 23 young (mean age 29 years) volunteers. Plasma antipyrine half-life ( AP t 1 2 ) increased and plasma APCl declined with age. No significant difference between plasma- and saliva-derived parameters was found in either young or old subjects. However, the saliva/plasma ACCl ratio tended to increase with age. A highly significant correlation between saliva and plasma APCl or AP t 1 2 was found in young subjects. Values were less closely related in the elderly and the slope of the saliva/plasma APCl relationship was significantly different in both groups of subjects. Residual variance was higher in the regressions corresponding to the elderly. The findings in the study indicate that the relationship between saliva and plasma kinetics in young subjects becomes less reproducible with age.

Primary leiomyosarcoma of the liver is a rare entity and fewer than 100 cases have been reported in the medical literature. Even more unusual is the association with another previous tumour. We report the case of a 84-year-old man who had been treated for a gastric non-Hodgkin lymphoma two years previously. He presented with a painful mass in the right upper abdomen. An ultrasound scan showed a large mass in the right lobe of the liver and chest radiography showed pulmonary metastases. Liver biopsy was performed and immunohistochemical analysis revealed a malignant leiomyosarcoma. We discuss this case and review the available literature.

Objectives: we analyzed the characteristics of patients withgastric tumors diagnosed with multiple malignant primary neo-plasm (MMPN) in the Health District of Leon.Material and methods:using the information in the TumorRegistry at Leon Hospital patients selected were those with gastricneoplasms diagnosed between 1993 and 2002. A follow-up wasperformed until December 31, 2004, and the characteristics ofpatients diagnosed with a second neoplasm were analyzed.Results: MMPN prevalence was 1,96%; 56% of patients hada history of cancer in first-degree relatives. The most frequent sec-ond neoplasms were digestive (26%) and urologic (21%); 87% ofpatients were diagnosed with a second neoplasm within the firsttwo years. No significative differences in survival were observedamong patients with synchronous or metachronous MMPN.Conclusions: MMPN in patients with gastric neoplasms is arelevant problem. While external carcinogenic agents could act aspromoters in the development of second neoplasms, these pa-tients seem to have a genetic background favoring the develop-ment of MMPN. Secondary prevention is the best measure toavoid MMPN development.Key words:Multiple neoplasms. Synchronous. Metachronous.Prostate. Survival. Prognosis. Oncology.

AIM: To evaluates the effectiveness and safety of the first generation, NS3/4A protease inhibitors (PIs) in clinical practice against chronic C virus, especially in patients with advanced fibrosis. METHODS: Prospective study and non-experimental analysis of a multicentre cohort of 38 Spanish hospitals that includes patients with chronic hepatitis C genotype 1, treatment-naive (TN) or treatment-experienced (TE), who underwent triple therapy with the first generation NS3/4A protease inhibitors, boceprevir (BOC) and telaprevir (TVR), in combination with pegylated interferon and ribavirin. The patients were treatment in routine practice settings. Data on the study population and on adverse clinical and virologic effects were compiled during the treatment period and during follow up. RESULTS: One thousand and fifty seven patients were included, 405 (38%) were treated with BOC and 652 (62%) with TVR. Of this total, 30% (n = 319) were TN and the remaining were TE: 28% (n = 298) relapsers, 12% (n = 123) partial responders (PR), 25% (n = 260) null-responders (NR) and for 5% (n = 57) with prior response unknown. The rate of sustained virologic response (SVR) by intention-to-treatment (ITT) was greater in those treated with TVR (65%) than in those treated with BOC (52%) (P < 0.0001), whereas by modified intention-to-treatment (mITT) no were found significant differences. By degree of fibrosis, 56% of patients were F4 and the highest SVR rates were recorded in the non-F4 patients, both TN and TE. In the analysis by groups, the TN patients treated with TVR by ITT showed a higher SVR (P = 0.005). However, by mITT there were no significant differences between BOC and TVR. In the multivariate analysis by mITT, the significant SVR factors were relapsers, IL28B CC and non-F4; the type of treatment (BOC or TVR) was not significant. The lowest SVR values were presented by the F4-NR patients, treated with BOC (46%) or with TVR (45%). 28% of the patients interrupted the treatment, mainly by non-viral response (51%): this outcome was more frequent in the TE than in the TN patients (57% vs 40%, P = 0.01). With respect to severe haematological disorders, neutropaenia was more likely to affect the patients treated with BOC (33% vs 20%, P = 0.0001), and thrombocytopaenia and anaemia, the F4 patients (P = 0.000, P = 0.025, respectively). CONCLUSION: In a real clinical practice setting with a high proportion of patients with advanced fibrosis, effectiveness of first-generation PIs was high except for NR patients, with similar SVR rates being achieved by BOC and TVR.

We analyzed the characteristics of the patients with bladder neoplasms who developed a multiple malignant primary neoplasm (MMPN) in the health district of León, the impact on survival and the prognostic variables.We have used the data from the Tumor Registry of the Hospital of León and selected all those patients who were diagnosed of a bladder tumor between 1993 and 2002. They were classified into two groups: the first with 71 patients with MMPN and a second group with 159 patients with single bladder tumors diagnosed between 1996 and 1997.Incidence of MMPN was of 7.1 percent. More than half of the patients had familial oncologic background. The second most frequently diagnosed neoplasms were urologic, followed by gastrointestinal and respiratory. Survival of patients with MMPN was 21 percent lower than single neoplasms. Variables with prognosis significance were the stage of the second neoplasm, diagnosis of a second urologic neoplasm and surgery treatment for the second tumor.MMPN in patients with bladder tumors are frequent in our geographic area. The high frequency of familial oncologic antecedents in these patients suggest a genetic background. Prognosis of MMPN patients is worse than single tumors patients, but no differences were observed regarding prognosis in patients with synchronous or metachronous MMPN.