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Introducción: La anatomía hepática siempre ha sido un reto por su complejidad y variabilidad. En los últimos años, el abaratamiento de los costes ha permitido la generación de modelos 3D individualizados para cada paciente que pueden facilitar el abordaje quirúrgico de las lesiones. El objetivo principal fue determinar la utilidad del modelado 3D preoperatorio para la planificación quirúrgica en pacientes con lesiones hepáticas. Métodos: Se trata de un estudio de casos de 38 pacientes intervenidos por lesiones hepáticas múltiples ocupantes de espacio, en el cual, en un grupo seleccionado, en 19 pacientes se utilizó un modelo impreso 3D para planificar la cirugía (grupo 3D) y el otro grupo sin el modelo impreso 3D (grupo control). Resultados: Se observó una diferencia de medias significativa en el número de lesiones; mayor en el grupo 3D al realizar el test de Wilcoxon (p < 0,001) y un mayor número de casos con afectación vascular en este mismo grupo al realizar Chi cuadrado Pearson (p = 0,008). El resto de variables no mostraron diferencias estadísticamente significativas. A pesar de esto, la mortalidad se redujo a 0 cuando se usan modelos impresos en 3D. Conclusión: La impresión 3D permite planear, de manera más precisa, cirugías complejas del hígado, ayuda a la inclusión y exclusión de los pacientes para la cirugía, disminuyendo el tiempo de la sala de operaciones, la posterior hospitalización y las complicaciones quirúrgicas.
Introduction: Liver anatomy has always been a challenge due to its complexity and variability. In recent years, lower costs has allowed the generation of individualized 3D models for each patient, which can facilitate the surgical approach to liver lesions. The main objective was to determine usefulness of preoperative 3D modeling for surgical planning in patients with liver lesions. Methods: Quasi-experimental before-after study. 19 cases were included in which surgery was planned using a 3D printed model (13 bilobar hepatectomies, 3 of them with vascular involvement, and 6 unilobar hepatectomies, 1 of them with vascular involvement), and another 19 cases whose planning was carried out without a 3D printed model (7 bilobar segmental hepatic resections and 12 unilobar segmental resections. None of these cases had vascular involvement). Results: A significant difference in mean lesion count was observed, higher in the group of cases when performing the Wilcoxon test (p < 0.001), and a higher number of cases with vascular involvement in the same group when performing the Pearson chi-square test (p = 0.008). The rest of the variables did not show statistically significant differences. Despite this, mortality was reduced to 0 when 3D printed models were used. Conclusion: 3D printing allows for more precise planning of complex liver surgeries, helps with the inclusion and exclusion of patients for surgery, reduces operating room time, postoperative hospitalization, and surgical complications.
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The widespread uptake of different machine perfusion (MP) strategies for liver transplant has been driven by an effort to minimize graft injury. Damage to the cholangiocytes during the liver donation, preservation, or early posttransplant period may result in stricturing of the biliary tree and inadequate biliary drainage. This problem continues to trouble clinicians, and may have catastrophic consequences for the graft and patient. Ischemic injury, as a result of compromised hepatic artery flow, is a well-known cause of biliary strictures, sepsis, and graft failure. However, very similar lesions can appear with a patent hepatic artery and these are known as ischemic type biliary lesions (ITBL) that are attributed to microcirculatory dysfunction rather than main hepatic arterial compromise. Both the warm and cold ischemic period duration appear to influence the onset of ITBL. All of the commonly used MP techniques deliver oxygen to the graft cells, and therefore may minimize the cholangiocyte injury and subsequently reduce the incidence of ITBL. As clinical experience and published evidence grows for these modalities, the impact they have on ITBL rates is important to consider. In this review, the evidence for the three commonly used MP strategies (abdominal normothermic regional perfusion [A-NRP], hypothermic oxygenated perfusion [HOPE], and normothermic machine perfusion [NMP] for ITBL prevention has been critically reviewed. Inconsistencies with ITBL definitions used in trials, coupled with variations in techniques of MP, make interpretation challenging. Overall, the evidence suggests that both HOPE and A-NRP prevent ITBL in donated after circulatory death grafts compared to cold storage. The evidence for ITBL prevention in donor after brain death grafts with any MP technique is weak.
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Sistema Biliar , Trasplante de Hígado , Humanos , Trasplante de Hígado/efectos adversos , Trasplante de Hígado/métodos , Microcirculación , Preservación de Órganos/métodos , Isquemia/etiología , Isquemia/prevención & control , Donantes de Tejidos , Perfusión/métodosRESUMEN
BACKGROUND: We studied the determinants of hemodynamics and analyzed the incidence, risk factors, and clinical impact of pulmonary homograft dysfunction following Ross surgery, after a 20-year follow-up at our referral center. METHODS: From 1997 to 2017, a total of 142 patients underwent surgery using the Ross procedure. The development of moderate-severe stenosis (peak transhomograft pressure gradient 36 mm Hg or greater) and surgical or percutaneous Ross homograft reinterventions were evaluated by echocardiography in the immediate postoperative period and at annual intervals. RESULTS: After 20 years of follow-up, 31% of patients had moderate-severe homograft stenosis, and 9.1% had had to undergo one or two reinterventions, of which, six were valve replacements and seven were percutaneous interventions. At 1, 5, and 20 years, 89.4%, 74.6%, and 69% of these patients, respectively, were free from moderate-severe stenosis; and 99.3%, 95.7%, and 90.9%, respectively, had freedom from homograft reintervention. The pediatric group had a higher risk factor for homograft stenosis (hazard ratio 3.70; 95% confidence interval, 1.56 to 7.20, P = .002), whereas donor age behaved as a protective factor (hazard ratio 0.98; 95% confidence interval, 0.95 to 0.99; P = .044). Pulmonary homograft stenosis tended to appear in the first year (10.6%) or at 5 years (25.4%). CONCLUSIONS: Pulmonary homografts implanted in the Ross procedure offer satisfactory long-term results, but the level of homograft dysfunction is not negligible. Young recipient and donor age were associated with a higher rate of homograft stenosis during follow-up. Moreover, homograft dysfunction usually occurred during the first few years of follow-up, and may have been related to immune responses.
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Procedimientos Quirúrgicos Cardíacos/efectos adversos , Predicción , Enfermedades de las Válvulas Cardíacas/cirugía , Disfunción Primaria del Injerto/diagnóstico , Válvula Pulmonar/cirugía , Adolescente , Adulto , Anciano , Aloinjertos , Niño , Preescolar , Ecocardiografía , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Disfunción Primaria del Injerto/cirugía , Reoperación , Estudios Retrospectivos , Factores de Riesgo , Adulto JovenAsunto(s)
Equinococosis Hepática/diagnóstico , Equinococosis/diagnóstico , Pericarditis/diagnóstico , Pericarditis/parasitología , Anciano , Antiprotozoarios/uso terapéutico , Diagnóstico Diferencial , Equinococosis/tratamiento farmacológico , Femenino , Humanos , Imagen por Resonancia Magnética , Pericarditis/tratamiento farmacológico , Resultado del TratamientoRESUMEN
BACKGROUND: Acute kidney injury (AKI) after liver transplantation (LT) is a common problem with complex management. The aims were to analyze the profile of AKI-RIFLE categories in the post-transplant setting of a wide multicentre cohort of patients in the MELD era and to specifically determine the effect of tacrolimus-based (TACRO) immunosuppressive regimes on the development of AKI. METHODS: A retrospective analysis of 550 (2007-2012) consecutive patients transplanted at Reina Sofia, Cordoba, and King's College Hospital, London, was performed. Inclusion criterion was to have CNI as part of initial immunosuppression immediately after LT. RESULTS: After exclusion criteria, a total of 477 patients were analyzed. Incidence of AKI within the first 2 weeks after LT was 65.8% (AKI-Risk), 41.3% (AKI-Injury), and 12.3% (AKI-Failure). The development of any type of AKI had no impact on short- and/or long-term survival up to 3 years after the transplant. Moreover, AKI was almost universal in the early post-transplant period and TACRO trough concentrations during the first 2 weeks after the transplant were not predictors of AKI in none of its categories in the multivariate analyses. CONCLUSIONS: Low-TACRO-based regimes were not as useful as expected in the prevention of AKI when analyzed in the context of a large contemporary LT series.
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Lesión Renal Aguda , Trasplante de Hígado , Lesión Renal Aguda/epidemiología , Lesión Renal Aguda/etiología , Humanos , Inmunosupresores/efectos adversos , Trasplante de Hígado/efectos adversos , Estudios Retrospectivos , Factores de Riesgo , Tacrolimus/efectos adversosRESUMEN
INTRODUCTION: Introduction: a survey on peri-operative nutritional support in pancreatic and biliary surgery among Spanish hospitals in 2007 showed that few surgical groups followed the 2006 ESPEN guidelines. Ten years later we sent a questionnaire to check the current situation. Methods: a questionnaire with 21 items sent to 38 centers, related to fasting time before and after surgery, nutritional screening use and type, time and type of peri-operative nutritional support, and number of procedures. Results: thirty-four institutions responded. The median number of pancreatic resections (head/total) was 29.5 (95% CI: 23.0-35; range, 5-68) (total, 1002); of surgeries for biliary malignancies (non-pancreatic), 9.8 (95% CI: 7.3-12.4; range, 2-30); and of main biliary resections for benign conditions, 10.4 (95% CI: 7.6-13.3; range, 2-33). Before surgery, only 41.2% of the sites used nutritional support (< 50% used any nutritional screening procedure). The mean duration of preoperative fasting for solid foods was 9.3 h (range, 6-24 h); it was 6.6 h for liquids (range, 2-12). Following pancreatic surgery, 29.4% tried to use early oral feeding, but 88.2% of the surveyed teams used some nutritional support; 26.5% of respondents used TPN in 100% of cases. Different percentages of TPN and EN were used in the other centers. In malignant biliary surgery, 22.6% used TPN always, and EN in 19.3% of cases. Conclusions: TPN is the commonest nutrition approach after pancreatic head surgery. Only 29.4% of the units used early oral feeding, and 32.3% used EN; 22.6% used TPN regularly after surgery for malignant biliary tumours. The 2006 ESPEN guideline recommendations are not regularly followed 12 years after their publication in our country.
INTRODUCCIÓN: Introducción: realizamos una encuesta sobre soporte nutricional perioperatorio en cirugía pancreática y biliar en hospitales españoles en 2007, que mostró que pocos grupos quirúrgicos seguían las guías de ESPEN 2006. Diez años después enviamos un cuestionario para comprobar la situación actual. Métodos: treinta y ocho centros recibieron un cuestionario con 21 preguntas sobre tiempo de ayunas antes y después de la cirugía, cribado nutricional, duración y tipo de soporte nutricional perioperatorio, y número de procedimientos. Resultados: respondieron 34 grupos. La mediana de pancreatectomías (cabeza/total) fue de 29,5 (IC 95%: 23,0-35; rango, 5-68) (total, 1002), la de cirugías biliares malignas de 9,8 (IC 95%: 7,3-12,4; rango, 2-30) y la de resecciones biliares por patología benigna de 10,4 (IC 95%: 7,6-13,3; rango, 2-33). Solo el 41,2% de los grupos utilizaban soporte nutricional antes de la cirugía (< 50% habian efectuado un cribado nutricional). El tiempo medio de ayuno preoperatorio para sólidos fue de 9,3 h (rango, 6-24 h), y de 6,6 h para líquidos (rango, 2-12). Tras la pancreatectomía, el 29,4% habían intentado administrar una dieta oral precoz, pero el 88,2% de los grupos usaron algún tipo de soporte nutricional y el 26,5% usaron NP en el 100% de los casos. Los demás grupos usaron diferentes porcentajes de NP y NE en sus casos. En la cirugía biliar maligna, el 22,6% utilizaron NP siempre y NE en el 19,3% de los casos. Conclusiones: la NP es el soporte nutricional más utilizado tras la cirugía de cabeza pancreática. Solo el 29,4% de las unidades usan nutrición oral precoz y el 32,3% emplean la NE tras este tipo de cirugía. El 22,6% de las instituciones usan NP habitualmente tras la cirugía de tumores biliares malignos. Las guías ESPEN 2006 no se siguen de forma habitual en nuestro país tras más de 10 años desde su publicación.
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Apoyo Nutricional/métodos , Pancreatectomía/normas , Procedimientos Quirúrgicos del Sistema Biliar , Humanos , Persona de Mediana Edad , Estado Nutricional , Páncreas , España , Encuestas y CuestionariosRESUMEN
BACKGROUND AND AIMS: Biliary anastomosis is a frequent area of complications after liver transplantation (LT) and a potential area of "microangiopathy". The concept of a "marginal bile duct" is unexplored. The main aim was to make a preliminary evaluation of the utility of an innovative real-time oxygen microtension (pO2mt) testing device for the assessment of bile duct viability during LT and to correlate these pO2mt values with microvascular tissue quality by histopathology and outcomes. PATIENTS AND METHODS: Observational prospective cohort study with 23 patients. Oxygen microtension measurements were made placing a micropO2 probe in different areas of recipient and donor's bile duct intraoperative. RESULTS: Mean pO2mt in the graft bile duct at the level of the anastomosis 103.82 (31-157) mm Hg, being 121.52 (55-174) mm Hg 1.5 cm proximal to the hilar plate (P < 0.001). Mean pO2mt in the recipient's bile duct was 117.87 (62-185) mm Hg, while a value of 137.30 (81-198) mm Hg was observed 1.5 cm distal to the anastomosis (P < 0.001). Cystic duct resection (12 cases) was also related with higher pO2mt values at anastomosis [117.8 (93-157) vs 88.54 (31-124) mm Hg] and distal to anastomosis [135.6 (111-174) vs 106.2 (55-133) mm Hg; P < 0.001]. Patients with 1-, 3-, and 12-month biliary complications had significantly lower pO2mt in the intraoperative measurements. CONCLUSION: Our preliminary results show that distal borders of donor and recipient bile ducts may be low-vascularized areas. Tissue pO2mt is significantly higher in areas close to the hilar plate and to the duodenum in donor and recipient's sides, respectively. Bile duct injury and biliary complications are associated with worse tissue pO2mt.
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Anastomosis Quirúrgica/efectos adversos , Enfermedades de las Vías Biliares/diagnóstico , Sistema Biliar/metabolismo , Complicaciones Intraoperatorias/diagnóstico , Trasplante de Hígado/efectos adversos , Donadores Vivos/provisión & distribución , Oxígeno/metabolismo , Sistema Biliar/patología , Enfermedades de las Vías Biliares/etiología , Enfermedades de las Vías Biliares/metabolismo , Femenino , Estudios de Seguimiento , Humanos , Complicaciones Intraoperatorias/etiología , Complicaciones Intraoperatorias/metabolismo , Masculino , Persona de Mediana Edad , Oxígeno/efectos adversos , Oxígeno/análisis , Pronóstico , Estudios Prospectivos , Factores de RiesgoRESUMEN
INTRODUCTION: The aim of this study is to identify factors associated to recurrence and survival in primary retroperitoneal liposarcomas. METHODS: Prospective database of 35 patients with primary retroperitoneal liposarcoma treated 2004-2015 were retrospectively analyzed. Exclusion criteria were recurrent and metastatic tumors. Overall survival (OS) and disease-free survival were reviewed. Patient data were compared between patients with or without recurrence within 12 months after surgery. Risk factors were determined using logistic regression analysis. RESULTS: Five-year OS was 61.1%. One and three-year disease-free survival were 68.6% and 17.1% respectively. OS in the early recurrence group was 36.4 months compared with 43.2 months in the group without early recurrence (P=.011). Early recurrence was associated with a reduction in OS (HR=4.05; CI95%: 1.27-12.96; P=.018). Multifocality and microscopic positive margins R1 were associated with early recurrence. Histologic subtype, margin of resection, histologic grade and multifocality were factors associated with recurrence. Contiguously involved organ resection had a beneficial effect on early recurrence and was associated with an increase in disease-free survival and OS. Adjuvant treatments had no protective effect on recurrence. CONCLUSIONS: This study underlines the crucial role aggressive surgical approach in retroperitoneal Liposarcoma treatment, especially in those patients with histological characteristics that adversely the prognosis.
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Liposarcoma/epidemiología , Recurrencia Local de Neoplasia/epidemiología , Neoplasias Retroperitoneales/epidemiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Factores de TiempoRESUMEN
Polyarteritis nodosa (PAN) is one of the systemic vasculitis that affects the media wall of arteries of small and medium diameter. Diagnosis proves difficult due to the unspecific symptoms that dominate the clinical profile. Liver involvement is very diverse, ranging from the development of cirrhotic liver disease to acute abdomen presentation that requires surgery because of liver rupture. The management of these patients requires an expert multidisciplinary team. There are several cases in the literature that describe a sudden liver rupture as the first manifestation of a PAN. In this paper we present the case of a 75 years old patient without any previous disease, who is subjected to major hepatic resection for spontaneous liver rupture.
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Hepatocellular carcinoma (HCC) is one of the most common and lethal cancers in the world, with limited options for treatment unless timely diagnosed. Chronic hepatitis C virus (HCV) infection and persistent heavy alcohol consumption are independent risk factors for HCC development, which may induce a specific protein expression pattern different from those caused separately. The aim of the study was to identify protein biomarkers for the detection of HCC in HCV-infected alcoholic patients with cirrhosis in order to improve survival. We compared protein expression profiles of plasma samples from 52 HCV-infected alcoholic patients with and without HCC, using 2-D DIGE coupled with MALDI-TOF/TOF mass spectrometry. The 2-D DIGE results were analyzed statistically using Decyder software, and verified by western-blot and ELISA. In plasma samples from HCV-infected alcoholic patients, we found significantly differential expression profiles of carboxypeptidase-N, ceruloplasmin (CP), complement component 4a (C4a), fibrinogen-alpha (FGA), immunoglobulin mu chain C region, serum albumin, and serum paraoxonase/arylesterase 1 (PON1). Deregulation of plasma/serum levels of the identified proteins was associated to HCV, ethanol consumption, and/or HCC progression. In the validation through ELISA, C4a serum concentration was increased in HCC patients (2.4±1 ng/mg vs 1.8±0.6 ng/mg; p = 0.029), being the only independent predictor of HCC in the multivariate analysis (OR = 2.15; p = 0.015), with an AUROC = 0.70. The combination of C4a, FGA, CP and PON1 improved slightly the predictive ability of C4a alone (AUROC 0.81). In conclusion, we identified proteins related to acute-phase response, oxidative stress, or immune response, whose differential expression in plasma may be attributed to the presence of HCC. Among them, C4a, and its combination with CP, FGA and PON1, could be considered as potentially reliable biomarkers for the detection of HCC in HCV-infected alcoholic patients.
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Alcoholismo/complicaciones , Biomarcadores de Tumor/sangre , Carcinoma Hepatocelular/diagnóstico , Hepatitis C/complicaciones , Cirrosis Hepática/etiología , Neoplasias Hepáticas/diagnóstico , Western Blotting , Carcinoma Hepatocelular/sangre , Ensayo de Inmunoadsorción Enzimática , Hepatitis C/sangre , Humanos , Cirrosis Hepática/sangre , Neoplasias Hepáticas/sangre , Programas InformáticosAsunto(s)
Neoplasias de los Conductos Biliares/patología , Tumor Carcinoide/patología , Neoplasias de los Conductos Biliares/cirugía , Tumor Carcinoide/cirugía , Conducto Colédoco/patología , Femenino , Humanos , Laparotomía , Imagen por Resonancia Magnética , Resultado del Tratamiento , Adulto JovenRESUMEN
AIM: To report our experience with long-term outcomes after multimodal management therapy. METHODS: An observational retrospective study was performed containing seven patients with hepatoblastoma (Hbl) treated in our institution, a tertiary referral center, from 2003 to 2011. Demographic, preoperative, surgical, and outcome variables were collected. A survival analysis and a review of the current literature related to combination neoadjuvant chemotherapy and surgical resection on Hbl were performed. RESULTS: The median age at surgery was 14.4 mo, with a male to female ratio of 4:3. Pretext staging at diagnosis was as follows: stageâ I, 4 cases; stage II, 2 patients; and stage III, 1 case. Mean pretreatment tumor volume was 735 cm(3). Five out of seven patients received neoadjuvant chemotherapy according to SIOPEL-3 or SIOPEL-6 protocols. Tumor volume and alpha-fetoprotein levels significantly dropped after neoadjuvant therapy. Surgical procedures performed included hemihepatectomies, segmentectomies and atypical resection. All patients received chemotherapy after surgery. Median postoperative hospital stay was 8 d. All patients were alive and disease-free after a median follow-up period of 23 mo. With regards to the literature review, seventeen articles were found that were related to our search. CONCLUSION: Our series shows how multimodal management of Hbl, exhaustive control and a meticulous surgical approach leads to almost 100% complete resection with optimal postoperative results.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Hepatectomía , Hepatoblastoma/terapia , Neoplasias Hepáticas/terapia , Terapia Neoadyuvante , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Quimioterapia Adyuvante , Preescolar , Supervivencia sin Enfermedad , Femenino , Hepatectomía/efectos adversos , Hepatectomía/mortalidad , Hepatoblastoma/sangre , Hepatoblastoma/mortalidad , Hepatoblastoma/patología , Humanos , Lactante , Tiempo de Internación , Neoplasias Hepáticas/sangre , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/patología , Masculino , Terapia Neoadyuvante/efectos adversos , Terapia Neoadyuvante/mortalidad , Estadificación de Neoplasias , Estudios Retrospectivos , España , Centros de Atención Terciaria , Factores de Tiempo , Tomografía Computarizada por Rayos X , Resultado del Tratamiento , Carga Tumoral , alfa-Fetoproteínas/metabolismoAsunto(s)
Adenocarcinoma/secundario , Adenocarcinoma/cirugía , Hepatectomía/métodos , Neoplasias Hepáticas/secundario , Neoplasias Hepáticas/cirugía , Neoplasias Pulmonares/secundario , Neoplasias Pulmonares/cirugía , Neumonectomía/métodos , Neoplasias del Colon Sigmoide/patología , Diafragma , Femenino , Humanos , Persona de Mediana Edad , Reproducibilidad de los ResultadosRESUMEN
BACKGROUND: The current methods available for screening and detecting hepatocellular carcinoma (HCC) have insufficient sensitivity and specificity, and only a low percentage of diagnosis of small tumours is based on these assays. Because HCC is usually asymptomatic at potentially curative stages, identification of biomarkers for the early detection of HCC is essential to improve patient survival. AIM: The aim of this study was to identify candidate markers for HCC development in the plasma from hepatitis C virus (HCV)-infected cirrhotic patients. METHODS: We compared protein expression profiles of plasma samples from HCV-infected cirrhotic patients with and without HCC, using two-dimensional fluorescence difference gel electrophoresis (2-D DIGE) coupled with MALDI-TOF/TOF mass spectrometry. The 2-D DIGE results were analysed statistically using Decyder™ software, and verified by western blot and enzyme-linked immunosorbent assay (ELISA). RESULTS: In the plasma of HCV-infected HCC patients, we observed decreased expression of complement component 9, ficolin-3 (FCN3), serum amyloid P component (SAP), fibrinogen-gamma and immunoglobulin gamma-1 chain, and increased expression of vitronectin (VTN) and galectin-3 binding protein (G3BP) by DIGE analysis. ELISA confirmed DIGE results for VTN and G3BP but not for SAP or FCN3 in a larger patient population. CONCLUSIONS: The proteins VTN and SAP are candidate biomarkers for HCC development in HCV-infected cirrhotic patients.
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Biomarcadores de Tumor/sangre , Carcinoma Hepatocelular/diagnóstico , Hepatitis C/sangre , Cirrosis Hepática/virología , Neoplasias Hepáticas/diagnóstico , Anciano , Western Blotting , Carcinoma Hepatocelular/sangre , Diagnóstico Precoz , Electroforesis en Gel Bidimensional , Ensayo de Inmunoadsorción Enzimática , Femenino , Hepacivirus , Hepatitis C/complicaciones , Humanos , Cirrosis Hepática/sangre , Neoplasias Hepáticas/sangre , Masculino , Persona de Mediana Edad , Proteómica , Componente Amiloide P Sérico/química , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción , Vitronectina/sangreRESUMEN
BACKGROUND: Orthotopic liver transplantation (OLT) is currently the elective treatment for advanced liver cirrhosis and acute liver failure. Ischemia/reperfusion damage may jeopardize graft function during the postoperative period. Cardiotrophin-1 (CT-1) has demonstrated cytoprotective properties in different experimental models of liver injury. There is no evidence to demonstrate its potential use in the prevention of the ischemia/reperfusion injury that occurs during OLT. The present study is the first report to show that the administration of CT-1 to donors would benefit the outcome of OLT. MATERIALS AND METHODS: We tested the cytoprotective effect of CT-1 administered to the donor prior to OLT in an experimental pig model. Hemodynamic changes, hepatic histology, cell death parameters, activation of cell signaling pathways, oxidative and nitrosative stress, and animal survival were analyzed. RESULTS: Our data showed that CT-1 administration to donors increased animal survival, improved cardiac and respiratory functions, and reduced hepatocellular injury as well as oxidative and nitrosative stress. These beneficial effects, related to the activation of AKT, ERK, and STAT3, reduced caspase-3 activity and diminished IL-1ß and TNF-α expression together with IL-6 upregulation in liver tissue. CONCLUSIONS: The administration of CT-1 to donors reduced ischemia/reperfusion injury and improved survival in an experimental pig model of OLT.
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Citocinas/uso terapéutico , Trasplante de Hígado , Cuidados Preoperatorios/métodos , Sustancias Protectoras/uso terapéutico , Daño por Reperfusión/prevención & control , Recolección de Tejidos y Órganos , Animales , Biomarcadores/metabolismo , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/fisiología , Citocinas/farmacología , Esquema de Medicación , Hemodinámica/efectos de los fármacos , Hepatectomía , Mediadores de Inflamación/metabolismo , Estimación de Kaplan-Meier , Hígado/efectos de los fármacos , Hígado/metabolismo , Trasplante de Hígado/mortalidad , Estrés Oxidativo/efectos de los fármacos , Sustancias Protectoras/farmacología , Distribución Aleatoria , Daño por Reperfusión/etiología , Daño por Reperfusión/mortalidad , Fenómenos Fisiológicos Respiratorios/efectos de los fármacos , PorcinosRESUMEN
BACKGROUND: Liver resection is a feasible treatment for multiple liver diseases. There is no evidence about the impact of age on liver regeneration. OBJECTIVE: To assess the effect of age on liver regeneration in an experimental in vivo animal model of 70%-partial hepatectomy. METHODS: Forty young (Y) and old (O) Wistar male rats (n = 80) were distributed into four groups [controls (C), sham operated (SO), hepatectomy 6 h (H6), and 48 h (H48)]. Different morphometric and biochemical factors, oxidative and nitrosative stress, lipid peroxidation, cytokines kinetics, and histopathologic tissular parameters were determined. RESULTS: Early postoperative mortality was higher in aged rats (P = 0.049). Morphometric determinations, liver regeneration index, and total volume weight were favorable to young rats. Serum transaminase levels were higher in aged rats. Parameters of necrosis (measured by histopathologic injury [HI: 0-I-II-III]), regeneration (measured by bromodeoxyuridine-BrdU incorporation) and apoptosis (determined by the TDT-mediated dUTP nick end labeling-TUNEL) were well-synchronized in young rats. Parameters of oxidative stress such as reduced (GSH), oxidized (GSSG) glutathione and lipid peroxidation (measured by hepatic malondialdehyde -MDA-) were lower in young animals throughout the studied period. Nitrosative stress measured by nitric oxide (NO) end-products was higher in late stages in resected old rats. Pro-inflammatory cytokines (TNF- α) reached higher and earlier levels in aged rats while pro-regenerative cytokines (IL-6) were significantly higher in early stages for young rats and in late stages for aged rats. The levels of TGF-ß were higher in young rats. CONCLUSION: Liver regeneration is delayed and reduced in aged animals submitted to liver resection.
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Hepatectomía/mortalidad , Regeneración Hepática/fisiología , Hígado/fisiología , Animales , Hígado/patología , Masculino , Ratas , Ratas WistarRESUMEN
BACKGROUND: The involvement of bone marrow hematopoietic stem cells (BMHSC) mobilization during liver regeneration from hepatectomized patients is under debate. The main aim of this study was to investigate the role of BMHSC mobilization after hepatic resection in 33 patients with liver disease. METHODS AND RESULTS: Mobilization of CD34(+) BMHSC after 72 h of surgery was found in peripheral blood of some, but not all, of the hepatectomized patients. These CD34(+) cells co-expressed other stem cells markers. The patients without BMHSC mobilization showed high levels of circulating and liver tissue BMHSC (CD34(+) cells) previous to surgery. Therefore, two types of patients: "mobilizers" and "non-mobilizers" were distinguished based on the values of CD34(+) cells before and after surgery. Changes in cytokines involved in the hepatic regeneration (HGF and TGF-ß), and in BMHSC mobilization process (SCF, SDF-1, IL-12, or MMP-2), were detected in both groups. In addition, a higher activation previous to surgery of the SDF-1/CXCR4 axis in liver tissue was observed in non mobilizers patients compared to mobilizer patients. CONCLUSION: BMHSC mobilization seems to be associated with variations in the levels of cytokines and proteolytic enzymes involved in hepatic regeneration and bone marrow matrix degradation. Hepatectomy may be an insufficient stimulus for BMSHC mobilization. The pre-hepatectomy higher levels CD34(+) cells in peripheral blood and liver, associated to the activation of hepatic SDF-1/CXCR4 axis, suggest a BMHSC mobilization process previous to surgery in non mobilizer patients.
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Antígenos CD34/metabolismo , Movilización de Célula Madre Hematopoyética , Células Madre Hematopoyéticas/metabolismo , Regeneración Hepática/fisiología , Transducción de Señal/fisiología , Adolescente , Adulto , Anciano , Quimiocina CXCL12/sangre , Femenino , Células Madre Hematopoyéticas/fisiología , Hepatectomía , Factor de Crecimiento de Hepatocito/sangre , Humanos , Interleucina-12/sangre , Antígeno Ki-67/metabolismo , Hígado/metabolismo , Hígado/patología , Hígado/cirugía , Masculino , Metaloproteinasa 2 de la Matriz/sangre , Persona de Mediana Edad , Receptores CXCR4/sangre , Factor de Células Madre/sangre , Factor de Crecimiento Transformador beta/sangreRESUMEN
BACKGROUND/PURPOSE: Rifampicin has been used for the treatment of patients with jaundice and pruritus. This study evaluated the effect of rifampicin on the expression of different detoxification systems and bile acid transporters during in-vivo and in-vitro experimental models of cholestasis. METHODS: Rifampicin was administered to glycochenodeoxycholic acid (GCDCA)-treated human hepatocytes and bile duct-obstructed rats. Different parameters related to cell death, and the expression of phase I and II drug metabolizing enzymes (DME) and bile acid transporters were determined. RESULTS: The induction of hepatocellular injury induced by cholestasis was associated with a reduction in cytochrome P4503A4 (CYP3A4), CYP7A1, and UDP-glucuronosyltransferase 2B4 (UGT2B4) expression, as well as an increase in import (Na(+)-taurocholate co-transporting polypeptide, NTCP) system expression. The beneficial properties of rifampicin were associated with an increase in DME and export bile acid systems (multidrug resistance-associated protein 4, MRP4, and bile acid export pump to bile duct, BSEP) expression, as well as a reduction in NTCP expression. CONCLUSIONS: The beneficial effect of rifampicin in cholestasis is associated with an increase in DME expression involved in toxic, bile acid and cholesterol metabolism, as well as a reduction in the bile acid importing system in hepatocytes.
Asunto(s)
Proteínas Portadoras/genética , Colestasis/tratamiento farmacológico , Regulación de la Expresión Génica , Glicoproteínas de Membrana/genética , ARN Mensajero/genética , Rifampin/farmacología , Animales , Apoptosis , Ácidos y Sales Biliares/metabolismo , Proteínas Portadoras/biosíntesis , Proteínas Portadoras/efectos de los fármacos , Células Cultivadas , Enfermedad Hepática Inducida por Sustancias y Drogas/tratamiento farmacológico , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Enfermedad Hepática Inducida por Sustancias y Drogas/patología , Colestasis/genética , Colestasis/metabolismo , Modelos Animales de Enfermedad , Inhibidores Enzimáticos/farmacología , Femenino , Ácido Glicoquenodesoxicólico/toxicidad , Hepatectomía , Hepatocitos/efectos de los fármacos , Hepatocitos/metabolismo , Hepatocitos/patología , Humanos , Masculino , Glicoproteínas de Membrana/biosíntesis , Glicoproteínas de Membrana/efectos de los fármacos , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , ARN Mensajero/metabolismo , Ratas , Ratas WistarRESUMEN
Hepatorenal syndrome (HRS) is a complication of cirrhosis with a poor prognosis without transplantation. The aim of this study is to analyze the influence of extended criteria donors (ECD) on the postoperative outcome of recipients with HRS. The last 498 patients were divided according to pre-transplant type 1 or 2 HRS. Sixty-six (13.25%) recipients fulfilled HRS criteria. Three-month graft survival was 84% with at-listing recipient serum creatinine ranging from 0-0.8 mg/dL; 80% with s-creatinine = 0.9-1.5 mg/dL; 79% with s-creatinine = 1.6-2.5 mg/dL; and 58% with s-creatinine >2.6 mg/dL (log-rank = 18.039; p = 0.001). Recipients with HRS presented higher levels of pre-transplant creatinine and lower levels of sodium, more episodes of hemodialysis and ascitis, and higher model of end-stage liver disease-scores. Three-month graft survival in recipients with HRS relative to ECD-variables showed differences in univariate analysis according to graft steatosis (85% in absent steatosis = 0-10%; 78% in mild steatosis = 10-30%; 76% in moderate steatosis = 30-60%; and 49% when severe steatosis >60%; log-rank = 5.146; p = 0.023). Cox-proportional-hazard-model revealed that graft macrosteatosis per-30%-increments (p = 0.000; HR = 1.303 [1.24-1.33] per-30%-increment) and donors >65 yr (p = 0.089; HR = 1.622 [1.17-1.94]) were independent predictors of graft loss in recipients with HRS. In conclusion, the use of ECD in recipients with cirrhosis and HRS is a good option. However, grafts from moderate-to-severe steatosis and those from aged donors must be carefully allocated in candidates with HRS.