RESUMEN
Liver cirrhosis is a frequent consequence of the long clinical course of all chronic liver diseases and is characterized by tissue fibrosis and the conversion of normal liver architecture into structurally abnormal nodules. Portal hypertension is the earliest and most important consequence of cirrhosis and underlies most of the clinical complications of the disease. Portal hypertension results from an increased intrahepatic resistance combined with increased portal (and hepatic arterial) blood flow. The fibrotic and angio-architectural modifications of liver tissue leading to increased intrahepatic resistance and the degree of portal hypertension seem to be highly correlated until HVPG values of 10-12 mmHg are reached. At this stage, which broadly represents the turning point between 'compensated' and 'decompensated' cirrhosis, additional extra-hepatic factors condition the further worsening of PH. Indeed, a HVPG ≥10-12 mmHg represents a critical threshold beyond which chronic liver disease becomes a systemic disorder with the involvement of other organs and systems. The progressive failure of one of the fundamental functions of the liver, i.e. the detoxification of potentially harmful substances received from the splanchnic circulation and particularly bacterial end-products, is responsible for the establishment of a systemic pro-inflammatory state further accelerating disease progression. The biology of liver cirrhosis is characterized by a constant stimulus for hepatocellular regeneration in a microenvironment characterized by chronic inflammation and tissue fibrosis, thus representing an ideal condition predisposing to the development of hepatocellular carcinoma (HCC). In reason of the significant improvements in the management of the complications of cirrhosis occurred in the past 20 years, HCC is becoming the most common clinical event leading to patient death. Whereas evidence clearly indicates reversibility of fibrosis in pre-cirrhotic disease, the determinants of fibrosis regression in cirrhosis are not sufficiently clear, and the point at which cirrhosis is truly irreversible is not established, either in morphologic or functional terms. Accordingly, the primary end-point of antifibrotic therapy in cirrhotic patients should be the reduction of fibrosis in the context of cirrhosis with a beneficial impact on portal hypertension and the emergence of HCC.
Asunto(s)
Carcinoma Hepatocelular/etiología , Hipertensión Portal/complicaciones , Cirrosis Hepática/complicaciones , Cirrosis Hepática/patología , Neoplasias Hepáticas/etiología , Hígado/irrigación sanguínea , Humanos , Hipertensión Portal/fisiopatología , Neovascularización PatológicaRESUMEN
Hepatoblastoma, a rare embryonic tumor that may arise sporadically or in the context of hereditary syndromes (familial adenomatous polyposis and Beckwith-Wiedemann's) is the most frequent liver cancer of childhood. Deregulation of the APC/beta-catenin pathway occurs in a consistent fraction of hepatoblastomas, with mutations in the APC and beta-catenin genes implicated in familial adenomatous polyposis-associated and sporadic hepatoblastomas, respectively. Alterations in other cancer-related molecular pathways have not been reported. We investigated a series of 21 sporadic paraffin-embedded hepatoblastoma cases for mutations in the p53 (exons 5-8) and beta-catenin (exon 3) genes, loss of heterozygosity at APC, microsatellite instability and immunohistochemical expression of beta-catenin and of the two main mismatch repair proteins, MLH1 and MSH2. No loss of heterozygosity at APC was detected. We found mutations in beta-catenin and p53 in 4/21 (19%) and 5/21 (24%) cases respectively, beta-catenin protein accumulation in 14/21 cases (67%), microsatellite instability in 17/21 cases (81%), of which eight resulted positive for high-level of microsatellite instability (in four cases associated with loss of MLH1/MSH2 immunostaining). No correlations between involved molecular pathway(s) and hepatoblastoma histotype(s) emerged. This study confirms that beta-catenin deregulation is involved in sporadic hepatoblastoma and also suggests that mismatch repair defects and p53 mutations contribute to this rare liver cancer. Sporadic hepatoblastoma appears to be molecularly and phenotypically heterogeneous and may reflect different pathways of liver carcinogenesis.
Asunto(s)
Reparación de la Incompatibilidad de ADN , Regulación Neoplásica de la Expresión Génica , Hepatoblastoma/genética , Neoplasias Hepáticas/genética , Mutación , Proteína p53 Supresora de Tumor/genética , beta Catenina/genética , Proteínas Adaptadoras Transductoras de Señales/análisis , Niño , Preescolar , Análisis Mutacional de ADN , Exones , Femenino , Genes APC , Hepatoblastoma/química , Hepatoblastoma/patología , Humanos , Inmunohistoquímica , Lactante , Neoplasias Hepáticas/química , Neoplasias Hepáticas/patología , Pérdida de Heterocigocidad , Masculino , Inestabilidad de Microsatélites , Homólogo 1 de la Proteína MutL , Proteína 2 Homóloga a MutS/análisis , Proteínas Nucleares/análisis , Reacción en Cadena de la Polimerasa , Estudios Retrospectivos , beta Catenina/análisisRESUMEN
BACKGROUND: Blockade of costimulation and adhesion signaling is an attractive approach to interfere with graft rejection METHODS: Between January 1997 and May 1999, forty adults having benign liver diseases were included in a prospective, randomized study comparing tacrolimus plus low-dose short-term steroids without (n=20, TAC group) or with a 10-day course of antihuman CD2 monoclonal antibody (n=20, BTI group). RESULTS: At day 7, histological rejection expressed by mean Banff scores (2.3+/-1.6 vs. 5.4+/-1.6 in the TAC group; P<0.0001) and incidence of moderate to severe rejection (score>or=6) (0 vs. 10 [50%] in the TAC group; P<0.001) were significantly lower in the BTI group. Rejection was treated in 10% (two patients) of BTI patients during the first 3 months and in 15% during the whole follow-up and in 25% (five patients) of TAC patients (P=NS). None of the BTI-patients presented with an adverse event. Three-month, 1-year, and 5-year actual patient survival rates were 100%, 95%, and 95% in the BTI group and 100%, 100%, and 85% in the TAC group. Graft survival rates were 100%, 90%, and 90% in the BTI group and 95%, 95%, and 80% in the TAC group (P=NS). The mAb had no negative impact on infectious or tumor events. CONCLUSIONS: Antihuman CD2 monoclonal antibody is a safe immunosuppressive drug which has a favorable impact on early immunological follow-up of liver transplanted patients. The antibody had no impact on late patient and graft survival.
Asunto(s)
Anticuerpos Monoclonales/uso terapéutico , Antígenos CD2/inmunología , Inmunosupresores/uso terapéutico , Trasplante de Hígado/inmunología , Tacrolimus/uso terapéutico , Adulto , Anciano , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Rechazo de Injerto/epidemiología , Supervivencia de Injerto , Humanos , Incidencia , Infecciones/complicaciones , Fallo Hepático/complicaciones , Fallo Hepático/cirugía , Recuento de Linfocitos , Persona de Mediana Edad , Neoplasias/complicaciones , Periodo Posoperatorio , Esteroides/administración & dosificación , Esteroides/uso terapéutico , Análisis de SupervivenciaRESUMEN
BACKGROUND: Control of blood outflow from the liver has become mandatory to reduce back-bleeding and prevent air emboli in difficult liver resections when dealing with the hepatic veins. Selective control of the major hepatic veins rather than unselective vena cava clamping is preferable in most of these cases. Extrahepatic isolation of the left-middle hepatic veins has been considered for a long time to be a hazardous maneuver, and there is no general agreement about the technique that should be used. HYPOTHESIS: The purpose of this article is to describe a technique used by us for the isolation of the left-middle hepatic veins so that total or selective (hemihepatic) vascular exclusion of the liver can be performed without vena cava clamping. METHODS: The inferior approach is easily accomplished soon after the exposure of some anatomical landmarks, and a triangle is described in which a clamp is inserted or, alternatively, when one uses a superior approach, when the instrument tip exits to enable the veins' looping. CONCLUSION: Compared with other techniques, this approach is easier and safer to perform in nearly all cases, providing that there is no tumor located close to the vena cava or hepatic vein junction that contraindicates this maneuver.
Asunto(s)
Hepatectomía/métodos , Venas Hepáticas/cirugía , Hígado/irrigación sanguínea , Procedimientos Quirúrgicos Vasculares/métodos , Humanos , Hígado/cirugíaRESUMEN
BACKGROUND: Pancreato-enteric reconstruction after pancreatoduodenectomy (PD) is still a source of debate because of the high incidence of complications. Among the various types of pancreato-jejunostomies we don't know yet which is the best in terms of anastomotic failure and related complications rates. Wirsung-jejunal duct-to-mucosa anastomosis (WJ) and "dunking" pancreato-jejunal anastomosis (DPJ) are the two most used ones worldwide but conflicting results are reported. To determine which is the safer anastomosis and to define when an anastomosis should be preferred, we retrospectively reviewed two groups of patients who underwent WJ or DPJ. METHODS: Twenty-three patients underwent PD with WJ (n = 17) with dilated (WJD) (n = 9) or not-dilated Wirsung's duct (WJND) (n = 8) or with a DPJ (n = 6) over a 3-year period at a single institution. RESULTS: The complications rate was high in all groups of patients (33.3% in WJD, 37.5% in WJND and 66.7% in DPJ). A pancreatic fistula developed in one patient in each group (11.1% in WJD, 12.5% in WJND and 16.7% in DPJ). All these patients were managed conservatively. Anastomotic disruption took place in the WJ patients especially in the WJND group (n = 2) compared to the WJD (n = 1) (25% vs. 11.1%) or DPJ groups (0%): these three patients required a re-operation. Overall, the anastomotic defects were higher in patients who underwent WJND (37.5%), compared to WJD (22.2%) and to DPJ (16.7%). However, no statistical differences were found among the groups. Delayed gastric emptying (DGE) and total parenteral nutrition (TPN) along with anastomotic defects were responsible for a prolonged hospital stay. CONCLUSIONS: Our results were not able to demonstrate any statistical difference between the two different techniques in preventing anastomotic failure. WJ can represent a valid choice in case of a dilated duct and a firm, fibrotic enlarged gland that could not be properly invaginated in a small jejunal loop. DGE may occur in those patients who experienced an anastomotic failure and required a TPN regimen with a prolonged hospital stay.
Asunto(s)
Mucosa Intestinal/cirugía , Yeyuno/cirugía , Pancreaticoduodenectomía , Pancreatoyeyunostomía/métodos , Adulto , Anciano , Anastomosis Quirúrgica/métodos , Femenino , Vaciamiento Gástrico , Humanos , Incidencia , Tiempo de Internación , Masculino , Persona de Mediana Edad , Pancreatoyeyunostomía/efectos adversos , Nutrición Parenteral Total , Reoperación , Estudios Retrospectivos , Dehiscencia de la Herida Operatoria/epidemiología , Dehiscencia de la Herida Operatoria/cirugía , Factores de TiempoRESUMEN
BACKGROUND: Partial porto-systemic shunts have been popularized because of reported low rate of mortality and morbidity (especially encephalopathy, liver failure and occlusion). To further investigate these assumptions, we retrospectively reviewed the results of partial porta-caval shunts performed at different stages of liver disease. METHODS: Twenty-nine cirrhotic patients underwent a partial porta-caval shunt with a ringed polytetrafluoroethylene interposition prosthesis of 8-mm (20 patients) or 10-mm (9 patients) in diameter. Pre and post-shunt porta-caval pressure was measured in all patients. Twelve patients (41.4%) belonged to Child A, 11 Child B (37.9%), and 6 Child C (20.7%). Eleven patients (37.9%) suffered from hepatic encephalopathy preoperatively. Twelve patients (41%) were operated on in emergency/urgency. RESULTS: Porta-caval pressure gradient, reduced significantly using either 8- or 10-mm prosthesis. The overall early mortality and morbidity were 13.8% and 48% respectively. The early mortality and morbidity were different between patients of Child A and B when compared to those of Child C (0 vs 66.6% and 34.8% vs 66.6% respectively). No patient re-bled early from varices. The overall late mortality and morbidity were 40% and 64% respectively. Shunt thrombosis and stenosis took place in 16% and 8% of the two groups of patients respectively; variceal re-bleeding occurred in 4 patients (16%). Encephalopathy occurred postoperatively in 5 patients (20%), acute in 3 patients (12%), and chronic in 2 (8%). The actuarial survival rate at 3 and 5 years was 92% and 75% for patients of Child A, 70% and 60% for patients of Child B, and 0% for patients of Child C. CONCLUSIONS: Our results indicate that partial porta-caval shunt with a small diameter interposition H-graft is an effective procedure for the treatment of variceal bleeding, as well as for the prevention of re-bleeding in patients of Child A and those of Child B, as an elective or emergency/urgency procedure, with a low rate of complications and encephalopathy. This technique could be used safely in patients with good liver function but they should be monitored closely because of the risk of shunt occlusion.