RESUMEN
AIM: To evaluate the utility of the portal venous phase on multiphasic computed tomography (CT) after treatment of hepatocellular carcinoma (HCC) with trans-arterial chemoembolisation (TACE). MATERIALS AND METHODS: This was a retrospective review of patients who underwent TACE for HCC between 1 April 2012 and 21 December 2014, with appropriate multiphasic, pre- and post-procedural CT examinations. The maximum non-contrast, arterial phase, and portal venous phase attenuation values of the tumour and tumour bed were evaluated within a region of interest (ROI), with values adjusted against background hepatic parenchyma. Linear regression analyses were performed for both the arterial and venous phases, to assess the level of enhancement and to determine if the venous phase had additional value in this setting. RESULTS: A total of 86 cases from 51 patients were reviewed. All pre-procedural CT examinations of lesions demonstrated arterial phase enhancement with portal venous and delayed phase washout compatible with HCC. The post-procedural CT examinations following TACE revealed expected decreased arterial enhancement. Sixty-five cases (76%) showed persistent non-enhancement on the portal venous phase following embolisation therapy. A total of 21 cases (24%), however, demonstrated progressive portal venous hyper enhancement. Linear regression analysis demonstrated a statistical significance between the difference in maximal arterial and portal venous enhancement in these cases. CONCLUSION: Following TACE, the treated lesion may demonstrate portal venous phase hyper-enhancement within the tumour bed. As such, full attention should be given to these images for comprehensive evaluation of tumour response following treatment.
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Carcinoma Hepatocelular/diagnóstico por imagen , Carcinoma Hepatocelular/terapia , Quimioembolización Terapéutica/métodos , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/terapia , Vena Porta/diagnóstico por imagen , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Tomografía Computarizada por Rayos X , Resultado del TratamientoRESUMEN
Background. Despite progress in surgical techniques applied during hepatobiliary and pancreas (HPB) surgery, bleeding and bile leak remain significant contributors to postoperative mortality and morbidity. Topical hemostatics have been developed and utilized across surgical specialties, but data regarding effectiveness remains inconsistent and sparse in HPB surgery. Methods. A comprehensive search for studies and reviews on hemostatics in HPB surgery was performed via an October 2011 query of Medline, EMBASE, and Cochrane Library. In-depth evaluation of a novel carrier-bound fibrin sealant (TachoSil) was also performed. Results. The literature review illustrates multiple attempts have been made at developing different topical hemostatics and sealants to aid in surgical procedures. In HPB surgery, efforts have been directed at decreasing bleeding, biliary leakage, and pancreatic fistula. Conflicting scientific evidence exists regarding the effectiveness of these agents. Critical evaluation of the literature demonstrates TachoSil is a valuable tool in achieving hemostasis, and possibly biliostasis and pancreatic fistula prevention. Conclusion. While progress has been made in topical hemostatics for HPB surgery, an ideal agent has not yet been identified. TachoSil is promising, but larger randomized, controlled clinical trials are required to more fully evaluate its efficacy in reducing bleeding, biliary leakage, and pancreatic fistulas in HPB surgery.
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Rechazo de Injerto/prevención & control , Supervivencia de Injerto/efectos de los fármacos , Trasplante de Corazón/inmunología , Inmunosupresores/farmacología , Terpenos/farmacología , Enfermedad Aguda , Monoterpenos Acíclicos , Animales , Prueba de Histocompatibilidad , Ratas , Ratas Endogámicas Lew , Ratas Endogámicas WF , Factores de Tiempo , Trasplante HomólogoRESUMEN
BACKGROUND: The overexpression of transforming growth factor-beta (TGF-beta) in hepatocellular carcinoma (HCC) appears to induce immunosuppression toward the tumor cells. METHODS: A rat HCC cell line, Morris hepatoma rat cell line (MRH)-7777 (MRH), was transfected with antisense TGF-beta2 in pCEP-4 vector and used as immunotherapy against the development of wild-type tumors. An enzyme-linked immunosorbent assay (ELISA) confirmed that TGF-beta2 production was markedly lower for antisense modified cells as compared to wild-type tumor cells. Tumors were initiated by injecting MRH cells into the flanks of Buffalo rats. This was followed by biweekly vaccinations with irradiated MRH cells (unmodified, pCEP-4 alone, or antisense TGF-beta2 modified). RESULTS: In the group that received irradiated MRH unmodified cells, 55% of rats died from tumor burden, and 36% developed tumor regression. In the group that received irradiated MRH cells modified with pCEP-4 vector alone, 50% died from tumors and 33% had spontaneous regression. In animals treated with pCEP-4/TGF-beta antisense modified cells, none developed tumors. Cell-mediated cytotoxicity assays demonstrated a twofold increase in lytic activity in the effector cells of the animals treated with antisense modified cells. CONCLUSIONS: These results demonstrate the successful treatment of HCC tumors in rats by a HCC vaccine genetically altered with antisense TGF-beta2. Decreased production of TGF-beta in HCC vaccine enhances immunogenicity against wild-type HCC tumor cells.
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Carcinoma Hepatocelular/terapia , ADN sin Sentido/uso terapéutico , Inmunoterapia/métodos , Neoplasias Hepáticas Experimentales/terapia , Factor de Crecimiento Transformador beta/biosíntesis , Factor de Crecimiento Transformador beta/genética , Animales , Carcinoma Hepatocelular/patología , Citotoxicidad Inmunológica , ADN sin Sentido/administración & dosificación , Modelos Animales de Enfermedad , Ensayo de Inmunoadsorción Enzimática , Expresión Génica/efectos de los fármacos , Vectores Genéticos , Humanos , Inyecciones Subcutáneas , Neoplasias Hepáticas Experimentales/patología , Trasplante de Neoplasias , Neoplasias/inducido químicamente , Plásmidos , Ratas , Ratas Endogámicas BUF , Retroviridae , Factor de Crecimiento Transformador beta2 , Células Tumorales Cultivadas , VacunaciónRESUMEN
The optimal treatment for hepatocellular carcinoma (HCC) is surgical resection. However, only a small percentage of patients are operative candidates. CT-guided percutaneous radiofrequency ablation (RFA) has been shown to be efficacious in treatment of unresectable HCC. CT-guided RFA, however, may fail to detect small intrahepatic metastases and tumor thrombi, which thus minimizes possible gains from the procedure. Recent advances in laparoscopic ultrasound have greatly improved the accuracy in detecting intrahepatic HCC metastases many of which were missed by CT. Combining intraoperative laparoscopic ultrasound with laparoscopic RFA greatly utilizes advances in both fields and is technically feasible. Our objective is to introduce a novel operative combination of laparoscopic ultrasound with laparoscopic RFA in treatment of HCC. Childs class B patients with unresectable HCC were considered for this study. Twelve patients underwent laparoscopic ultrasound and RFA of 17 lesions. Tumors ranged from 0.27 to 7 cm in diameter. Laparoscopic ultrasound identified tumor not detected preoperatively in one patient (8.3%). A single pneumothorax was the only complication. A single patient (8.3%) had recurrent disease and accounted for the only mortality in the study. We conclude that the use of both laparoscopic ultrasound and RFA is an excellent use of existing technology. The procedure combines improved tumor localization with the means to treat patients with unresectable disease. Because RFA is a relatively recent development long-term results are not yet available. Randomized prospective studies comparing RFA with other modalities will determine the ultimate utility of this procedure.
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Carcinoma Hepatocelular/cirugía , Ablación por Catéter/métodos , Laparoscopía , Cirrosis Hepática/cirugía , Neoplasias Hepáticas/cirugía , Cirugía Asistida por Computador , Adulto , Anciano , Carcinoma Hepatocelular/complicaciones , Carcinoma Hepatocelular/diagnóstico por imagen , Humanos , Cirrosis Hepática/diagnóstico por imagen , Neoplasias Hepáticas/complicaciones , Neoplasias Hepáticas/diagnóstico por imagen , Persona de Mediana Edad , Tomografía Computarizada por Rayos X , UltrasonografíaRESUMEN
BACKGROUND: Common bile duct injuries occur in 0.2% to 0.8% of laparoscopic cholecystectomies (LC). Intraoperative cholangiograms (IOCG) are a useful means of detecting common bile duct injuries in the operating room. METHODS: Data were retrospectively reviewed for patients referred for management of common duct injuries from 1996 to 2000. Cost data were obtained from hospital records. Legal settlements were obtained from published sources. RESULTS: Twenty-one patients (0.133%) were found to have bile duct injuries and incurred median hospital stays of 11.5 days at an average cost of $587,491. The average cost of those requiring reoperation was $669,134. The 21 cases in our sample had total charges of $10,819,767. Performing IOCG during each LC in Orange County would have cost $10,669,725. If extrapolated to state and nationwide levels, the savings is far greater. CONCLUSIONS: IOCG during LC is a cost-effective means of preventing the costs of delayed recognition of bile duct injuries.
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Colangiografía/economía , Colecistectomía Laparoscópica/efectos adversos , Monitoreo Intraoperatorio/economía , Adulto , Conducto Colédoco/lesiones , Análisis Costo-Beneficio , Femenino , Humanos , Tiempo de Internación/economía , Masculino , Persona de Mediana Edad , Reoperación/economía , Estudios Retrospectivos , Estados UnidosAsunto(s)
Rechazo de Injerto/tratamiento farmacológico , Inmunosupresores/uso terapéutico , Enfermedades Renales/tratamiento farmacológico , Activación de Linfocitos/efectos de los fármacos , Monoterpenos , Pravastatina/uso terapéutico , Prenilación de Proteína/efectos de los fármacos , Linfocitos T/efectos de los fármacos , Terpenos/uso terapéutico , Animales , Evaluación Preclínica de Medicamentos , Rechazo de Injerto/inmunología , Hiperplasia , Inmunosupresores/farmacología , Enfermedades Renales/inmunología , Enfermedades Renales/patología , Pravastatina/farmacología , Ratas , Terpenos/farmacologíaRESUMEN
Perillyl alcohol (POH) inhibits isoprenylation and has shown anticancer and chemopreventive properties in rodent models. The mechanism that underlies the anticancer activity of POH and other isoprenylation inhibitors is unknown but has been postulated to involve decreased levels of isoprenylated Ras and Ras-related proteins. Previously we demonstrated that POH effectively inhibits human T cell proliferation in vitro and can prevent acute and chronic rejection in a rat cardiac transplant model. In this report, we investigate the effects of POH on T lymphocytes at the single-cell level. POH disrupts the polarized shape and motility of antigen-specific murine 1E5 T cells. Using an optical trap to position anti-CD3-coated beads in contact with 1E5 T cells, we demonstrate that POH inhibits their TCR-mediated calcium response. Furthermore, we show that POH preferentially induces apoptosis in PHA-activated human T cells as well as in 1E5 T cells.
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Transferasas Alquil y Aril/antagonistas & inhibidores , Apoptosis/efectos de los fármacos , Calcio/metabolismo , Movimiento Celular/efectos de los fármacos , Inhibidores Enzimáticos/farmacología , Monoterpenos , Receptores de Antígenos de Linfocitos T/metabolismo , Transducción de Señal/fisiología , Linfocitos T/efectos de los fármacos , Terpenos/farmacología , Adulto , Animales , Polaridad Celular/efectos de los fármacos , Tamaño de la Célula/efectos de los fármacos , Humanos , Ratones , Linfocitos T/metabolismo , Linfocitos T/fisiologíaAsunto(s)
Enfermedad Coronaria/prevención & control , Ciclosporina/uso terapéutico , Trasplante de Corazón/inmunología , Trasplante de Corazón/patología , Isoanticuerpos/sangre , Animales , Formación de Anticuerpos , Enfermedad Coronaria/etiología , Enfermedad Coronaria/inmunología , Inmunoglobulina G/sangre , Inmunoglobulina M/sangre , Inmunosupresores/uso terapéutico , Isoanticuerpos/biosíntesis , Complicaciones Posoperatorias , Ratas , Ratas Endogámicas F344 , Ratas Endogámicas Lew , Trasplante Homólogo/inmunologíaRESUMEN
Patients undergoing liver transplantation for hepatitis B-related liver disease are prone to recurrence. The mainstay of prophylaxis has been passive immunotherapy with hepatitis B immune globulin (HBIG). Antiviral therapy with lamivudine has proven effective in lowering hepatitis B virus (HBV) DNA and improving histology in patients with hepatitis B infection; its role in prophylaxis against hepatitis B recurrence following liver transplantation is under investigation. Viral breakthrough and resistance, however, are a significant problem with monotherapy with either HBIG or lamivudine. The efficacy of combination lamivudine/HBIG prophylaxis has not been reported. Fourteen patients underwent transplantation for decompensated liver disease owing to hepatitis B. Lamivudine (150 mg p.o./d) was begun before transplantation in 10 patients, including 4 who were HBV DNA-positive. In addition, 1 patient was HBV DNA-positive when transplanted. HBIG was given perioperatively and continued thereafter; treatment with lamivudine was maintained or initiated at the time of transplantation and continued indefinitely. The median follow-up was 387 days. Actuarial 1-year patient and graft survival was 93% (1 patient died of unrelated causes). At a median interval of 28 days following lamivudine treatment, all 5 HBV DNA-positive patients cleared HBV DNA from the serum; 1 went on to clear hepatitis B surface antigen (HBsAg), before transplantation, at day 148 of lamivudine treatment. By the highly sensitive polymerase chain reaction (PCR), at a median of 346 days (range, 130-525 days) following transplantation, all 13 surviving patients had no detectable serum HBV DNA. Lamivudine suppresses HBV replication in patients awaiting liver transplantation. At a median follow-up of 1.1 years, combination prophylaxis with lamivudine and HBIG prevented hepatitis B recurrence following liver transplantation.
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Hepatitis B/prevención & control , Inmunización Pasiva , Lamivudine/uso terapéutico , Trasplante de Hígado , Complicaciones Posoperatorias/prevención & control , Inhibidores de la Transcriptasa Inversa/uso terapéutico , Adulto , Anciano , Femenino , Estudios de Seguimiento , Hepatitis B/terapia , Hepatitis B/virología , Virus de la Hepatitis B/fisiología , Humanos , Inmunoglobulinas , Hígado/fisiopatología , Pruebas de Función Hepática , Masculino , Persona de Mediana Edad , Cuidados Posoperatorios , Cuidados Preoperatorios , Prevención Secundaria , Replicación Viral/efectos de los fármacosRESUMEN
OBJECTIVE: The authors' goal was to determine the effects of specific binding and blockade of P- and E-selectins by a soluble P-selectin glycoprotein ligand-1 (PSGL-1) in rat models of hepatic in vivo warm ischemia and ex vivo cold ischemia. The authors also sought to determine the effect of selectin blockade on isograft survival in a syngeneic rat orthotopic liver transplant model. SUMMARY BACKGROUND DATA: Ischemia/reperfusion (I/R) injury is a major factor in poor graft function after liver transplantation, which may profoundly influence early graft function and late changes. It is hypothesized that I/R injury leads to the upregulation of P-selectin, which is then rapidly translocated to endothelial cell surfaces within 5 minutes of reperfusion of the liver, initiating steps leading to tethering of polymorphonuclear neutrophil leukocytes to the vascular intima. Local production by leukocytes of interleukin-1, tumor necrosis factor-alpha, or both induces P-selectin expression on the endothelium and continues the cascade of events, which increases cell adherence and infiltration of the organ. METHODS: To examine directly the effects of selectins in a warm hepatic I/R injury model, 100 microg of PSGL-1 or saline was given through the portal vein at the time of total hepatic inflow occlusion. The effects of PSGL-1 in cold ischemia were assessed using an isolated perfused rat liver after 6 hours of 4 degrees C storage in University of Wisconsin (UW) solution, with or without the instillation of PSGL-1 before the storage. To evaluate the effect of selectin blockade on liver transplant survival, syngeneic orthotopic liver transplants were performed between inbred male Sprague-Dawley rats after 24 hours of cold ischemic storage in UW solution. A separate group of animals received two doses of 100 microg of PSGL-1 through the portal vein before storage and before reperfusion of the transplanted liver. Recipient survival was assessed at 7 days, and the Kaplan-Meier product limit estimate method was used for univariate calculations of time-dependent recipient survival events. RESULTS: In an in vivo warm rat liver ischemia model, perfusion with PSGL-1 afforded considerable protection from I/R injury, as demonstrated by decreased transaminase release, reduced histologic hepatocyte damage, and suppressed neutrophil infiltration, versus controls (p < 0.05). When cold stored livers were reperfused, PSGL-1 reduced the degree of hepatocyte transaminase release, reduced neutrophil infiltration, and decreased histologic hepatocyte damage (p < 0.05 vs. UW-only controls). On reperfusion, livers treated with PSGL-1 demonstrated increased portal vein blood flow and bile production (p < 0.05 vs. UW-only controls). In addition, 90% of the rats receiving liver isografts stored in UW solution supplemented with PSGL-1 survived 7 days versus 50% of those whose transplanted syngeneic livers had been stored in UW alone (p < 0.05). CONCLUSIONS: Selectins play an important role in I/R injury of the liver. Early modulation of the interaction between P-selectin and its ligand decreases hepatocyte injury, neutrophil adhesion, and subsequent migration in both warm and cold rat liver ischemia models. In addition, the use of PSGL-1 before ischemic storage and before transplantation prevents hepatic injury, as documented by a significant increase in liver isograft survival. These findings have important clinical ramifications: early inhibition of alloantigen-independent mechanisms during the I/R damage may influence both short- and long-term survival of liver allografts.
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Hepatopatías/prevención & control , Trasplante de Hígado , Glicoproteínas de Membrana/farmacología , Selectina-P/efectos de los fármacos , Daño por Reperfusión/prevención & control , Animales , Aspartato Aminotransferasas/metabolismo , Adhesión Celular , Ligandos , Hepatopatías/enzimología , Hepatopatías/patología , Masculino , Mucinas , Selectina-P/biosíntesis , Peroxidasa/metabolismo , Ratas , Ratas Sprague-Dawley , Daño por Reperfusión/enzimología , Daño por Reperfusión/patología , Solubilidad , Regulación hacia ArribaRESUMEN
A 55-year-old woman developed end-stage liver disease and the hepatorenal syndrome secondary to cryptogenic cirrhosis. Orthotopic liver transplantation was complicated by bile peritonitis, requiring reoperation and eventual placement of an internal biliary stent. On postoperative day 26, hemobilia was caused by localized rupture of mycotic (Aspergillus fumigatus) hepatic artery pseudoaneurysms with fistulization into the biliary tree. After arterial reconstruction with a reversed autologous saphenous vein graft, the patient was treated successfully with liposomal amphotericin B.
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Anfotericina B/administración & dosificación , Aneurisma Falso/terapia , Arteria Hepática/microbiología , Micosis/terapia , Portadores de Fármacos , Femenino , Arteria Hepática/diagnóstico por imagen , Arteria Hepática/patología , Humanos , Liposomas , Persona de Mediana Edad , RadiografíaRESUMEN
BACKGROUND: Pravastatin, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, inhibits coronary transplant vasculopathy in the clinical setting. To further delineate the immune modulatory effect of this agent, it was tested in a rat cardiac transplant model of chronic rejection. METHODS: Rat heterotopic abdominal cardiac transplants were performed using a Lewis to Fischer 344 combination. Fischer 344 recipients received a brief course of cyclosporine to decrease the incidence of acute rejection. Experimental groups were treated with either high-dose (10 mg/kg) or low-dose (5 mg/kg) pravastatin for 120 days, while a control group did not receive pravastatin. The effect of pravastatin on chronic rejection of cardiac allografts was analyzed by histology, and the expression of laminin, fibronectin, macrophages, and T cells was assessed by immunohistochemistry. RESULTS: Coronary transplant vasculopathy was inhibited in both groups of pravastatin-treated animals, as compared with controls. Immunohistochemistry revealed that control animals had degraded laminin and fibronectin which paralleled the degree of tissue necrosis. In contrast, pravastatin-treated animals had modest amounts of extracellular matrix proteins retained within intermyocytes and endothelium, a pattern seen in native cardiac tissue. The pravastatin-treated groups also had fewer graft-infiltrating macrophages, specifically within the arterial intima and perivascular areas. CONCLUSIONS: Progressive chronic vascular rejection, a leading cause of allograft failure, can be inhibited by pravastatin in a well-defined rat cardiac transplant model. Pravastatin appears to inhibit the synthesis and subsequent degradation of extracellular matrix proteins and block the infiltration of macrophages to the graft, which emphasizes that this inflammatory cell plays a major role in the pathogenesis of transplant chronic rejection.
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Rechazo de Injerto/prevención & control , Trasplante de Corazón/inmunología , Inhibidores de Hidroximetilglutaril-CoA Reductasas/farmacología , Pravastatina/farmacología , Animales , Proteínas de la Matriz Extracelular/metabolismo , Rechazo de Injerto/metabolismo , Rechazo de Injerto/patología , Trasplante de Corazón/patología , Inmunohistoquímica , Macrófagos , Masculino , Ratas , Ratas Endogámicas F344 , Ratas Endogámicas Lew , Trasplante HomólogoRESUMEN
BACKGROUND: Fas ligand (FasL) induces apoptosis of cells bearing its receptor Fas, and has been shown to be important in T-cell development and regulation and in immune privilege. We hypothesized that FasL expression by renal allografts might provide protection from rejection. METHODS: The murine FasL cDNA was cloned into a replication-defective adenovirus (AdV-FasL). Protein expression was confirmed by immunostaining of AdV-FasL-transduced HeLa cells. Allogeneic kidney transplants were performed between WF (RT1u) donors and Lewis (RT1) recipients. Donor kidneys were perfused in situ with saline alone (control), or 9 x 10(9) plaque-forming units of AdV-FasL. One native kidney was removed at the time of transplant and the other at 6 or 7 days. Uremic death was the endpoint, and deaths within 7 days of transplant were excluded. Transduced allografts were stained for FasL expression using a monoclonal antibody and tested for FasL mRNA production by reverse transcriptase-polymerase chain reaction and Northern blotting. RESULTS: Immunostaining of AdV-FasL-transduced allografts demonstrated efficient gene transfer lasting approximately 2 weeks, and FasL mRNA production in the AdV-FasL-transduced allografts was confirmed by Northern blotting and reverse transcriptase-polymerase chain reaction. Mean survival of animals with AdV-FasL-transduced renal allografts was 27.8 days vs. 11.6 days in control animals (P < 0.05). CONCLUSIONS: (1) Adenoviral vectors can successfully transduce rat kidneys with the FasL cDNA. (2) FasL gene transfer prolongs rat renal allograft survival.
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Citotoxicidad Inmunológica , Rechazo de Injerto/metabolismo , Supervivencia de Injerto , Trasplante de Riñón/inmunología , Glicoproteínas de Membrana , Trasplante Homólogo/inmunología , Adenoviridae , Animales , Citotoxicidad Inmunológica/genética , ADN Complementario , Proteína Ligando Fas , Técnicas de Transferencia de Gen , Rechazo de Injerto/inmunología , Rechazo de Injerto/prevención & control , Supervivencia de Injerto/genética , Supervivencia de Injerto/inmunología , Células HeLa , Humanos , Inmunohistoquímica , Trasplante de Riñón/patología , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/inmunología , Glicoproteínas de Membrana/metabolismo , Reacción en Cadena de la Polimerasa , ARN Mensajero/análisis , Ratas , Ratas Endogámicas Lew , Ratas Endogámicas WF , Transducción Genética , Trasplante Homólogo/patologíaRESUMEN
BACKGROUND: We retrospectively reviewed 213 consecutive patients who received their first liver allograft between January 1 and December 31, 1993, in order to study the impact of ischemia/preservation/reperfusion injury (IPRI) on patient and graft outcome. METHODS: The extent of IPRI was assessed by the peak value of aspartate aminotransferase (ASTmax) observed within the first 72 hr after transplant. For the purpose of univariate analysis, categorical classification of recipients was done based upon ASTmax as follows: group 1, ASTmax<600 U/L (n=46); group 2, ASTmax=600-2000 U/L (n=97); group 3, ASTmax>2000-5000 U/L (n=50), and group 4, ASTmax>5000 U/L (n=17). For multivariate analysis, stepwise Cox regression was performed with age, ASTmax, and United Network for Organ Sharing (UNOS) status as covariates. RESULTS: Groups were comparable with respect to age, UNOS status at the time of transplantation, and diagnostic case mix. Median follow-up was 644 days. The overall incidence of primary graft nonfunction (PNF) was 7.6%. PNF incidence was significantly correlated with the severity of IPRI (0%, 4%, 10%, and 41% for groups 1 to 4, respectively, P < 0.0001), but this impact was confined to the respective rates of retransplantation as early patient survival was unaffected. The 1-year survival of patients whose initial grafts manifested extreme IPRI (group 4) was significantly inferior to recipients in the three other groups (77%, 71%, 73%, and 52% for groups 1 to 4, respectively, P=0.03). This increased mortality was confined to patients who never achieved discharge from their initial hospitalization, with no significant differences between groups being detected in the survival of those patients who were discharged (84%, 80%, 85%, and 81% for groups 1 to 4, respectively, P=NS). Although overall 1-year graft survival was strongly correlated with the extent of IPRI (77%, 67%, 62%, and 41% for groups 1 to 4, respectively, P=0.001), this correlation was abolished when survival of grafts not lost to PNF was examined at 1 and 2 years. Stepwise Cox regression analysis confirmed the independent association between ASTmax and patient and graft survival. The long-term quality of allograft function as well as the incidence of chronic rejection and biliary complications were unrelated to the extent of IPRI. CONCLUSIONS: We conclude that: (1) patient survival is influenced by IPRI only when it is extreme (ASTmax>5000 U/L), provided parameters of graft function are used in conjunction with aminotransferase values to assess the need for prompt retransplantation; (2) short-term graft survival is proportional to the extent of IPRI, but grafts that are not lost to PNF have equivalent 1- and 2-year survival irrespective of the magnitude of IPRI; (3) 40% of grafts with extreme IPRI are lost to PNF, but the same proportion also provide long-term function; and (4) for surviving grafts, long-term biochemical function as well as the incidence of biliary complications and of chronic rejection are unrelated to the extent of IPRI.
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Aspartato Aminotransferasas/metabolismo , Trasplante de Hígado , Adulto , Sistema Biliar/fisiopatología , Ciclosporina/uso terapéutico , Femenino , Rechazo de Injerto/prevención & control , Supervivencia de Injerto/efectos de los fármacos , Humanos , Inmunosupresores/uso terapéutico , Hígado/enzimología , Trasplante de Hígado/fisiología , Masculino , Muromonab-CD3/uso terapéutico , Estudios Retrospectivos , Tacrolimus/uso terapéuticoRESUMEN
BACKGROUND: The shortage of cadaveric donor livers is the rate-limiting step in clinical liver transplantation. Split liver transplantation provides a means to expand the cadaveric donor pool. However, this concept has not reached its full potential because of inferior patient and graft survival and high complication rates when traditional ex vivo split techniques are used. Therefore we sought to evaluate the safety, applicability, and effectiveness of a new technique for split liver transplantation. METHODS: This study consists of 15 in situ split liver procurements, which resulted in 28 liver transplants. In situ splitting of selected livers from hemodynamically stable cadaveric donors was performed at the donor hospital without any additional work-up or equipment being needed. In situ liver splitting is accomplished in a manner identical to the living-donor procurement. This technique for liver splitting results in a left lateral segment graft (segments 2 and 3) and a right trisegmental graft (segments 1 and 4-8). This procedure required the use of the donor hospital operating room for an additional 1.5-2.5 hr and did not interfere with the procurement of 30 kidneys, 12 hearts, 7 lungs, and 9 pancreata from these same donors. RESULTS: The 6-month and 1-year actuarial patient survival rates were 92% and 92%, respectively, while the 6-month and 1-year actuarial graft survival rates were 86% and 86%, respectively. The 6-month and 1-year actuarial patient survival rate of patients who received a left lateral segment graft was 100% and 100%, respectively, while those who received a right trisegmental graft had 6-month and 1-year rates of 86% and 86%, respectively. The actuarial death-censored graft survival rates at 6 months and 1 year were 80% and 80%, respectively, for the left lateral segment grafts, and 93% and 93%, respectively, for the right trisegmental grafts. Alograft and patient survival was independent of United Network for Organ Sharing status at the time of liver transplantation. No patient developed a biliary stricture, required re-exploration for intra-abdominal hemorrhage, or suffered from portal vein, hepatic vein, or hepatic artery thrombosis CONCLUSIONS: In situ split liver transplantation can be accomplished without complications and provides results that are superior to those obtained previously with ex vivo methods. It abolishes ex vivo benching and prolonged ischemia times and provides two optimal grafts with hemostasis accomplished. This technique decreases pediatric waiting time and allows adult recipients to receive right-sided grafts safely. In situ splitting is the method of choice for expanding the cadaveric liver donor pool.
Asunto(s)
Supervivencia de Injerto , Hepatectomía/métodos , Trasplante de Hígado/métodos , Análisis Actuarial , Adulto , Cadáver , Corazón , Hemodinámica , Humanos , Riñón , Trasplante de Hígado/mortalidad , Trasplante de Hígado/fisiología , Donadores Vivos , Pulmón , Páncreas , Complicaciones Posoperatorias , Seguridad , Tasa de Supervivencia , Factores de Tiempo , Donantes de Tejidos/provisión & distribución , Obtención de Tejidos y Órganos/organización & administración , Estados UnidosRESUMEN
Pravastatin, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, has been shown to decrease the number of acute rejection episodes in cardiac and renal transplant patients. This study evaluates the effects of pravastatin on survival of rats following liver transplant and attempts to elucidate the mechanisms of these effects. Both survival and natural killer cell enhancing factor (NKEF) studies utilized Dark Agouti rats for donor livers transplanted into Brown Norway rats as recipients. All rats received daily low-dose cyclosporine (CsA) 2 mg/kg/day by gavage. The treated groups also received gavage doses of pravastatin, 20 mg/kg/day. Survival data were analyzed by the method of Kaplan-Meier and log-rank chi 2 tests for statistical significance. For NKEF evaluation, rats were sacrificed at varying time points; total RNA was extracted from the liver and hybridized with 32P-radiolabeled NKEF DNA probes in the Northern blot technique. Radiographs were quantitated using densitometry. Data were analyzed by two-way ANOVA. Actuarial survival was improved (P < < 0.05) in rats treated with pravastatin in addition to low-dose CsA (n = 41, CsA alone n = 74). Less fibrosis and chronic rejection was seen on histological section in the treated animal livers, P < 0.05, NKEF was seen maximally at Days 5-15 tapering off at Day 21. NKEF-a and NKEF-b levels were significantly decreased in the animals treated with CsA and pravastatin compared to CsA alone in the group of animals < 16 days postop (P < < 0.05). Pravastatin improves survival in rats following OLT and while the mechanism is still unknown, inhibition of natural killer cell enhancement factor may represent an alteration in the overall immune response.
Asunto(s)
Proteínas Sanguíneas/biosíntesis , Supervivencia Celular/efectos de los fármacos , Inhibidores Enzimáticos/farmacología , Inhibidores de Hidroximetilglutaril-CoA Reductasas , Inmunosupresores/farmacología , Células Asesinas Naturales/inmunología , Pravastatina/farmacología , Animales , Proteínas Sanguíneas/genética , Ciclosporina/administración & dosificación , Rechazo de Injerto/patología , Proteínas de Choque Térmico , Hígado/patología , Trasplante de Hígado/inmunología , Trasplante de Hígado/patología , Peroxidasas , Peroxirredoxinas , Ratas , Ratas Endogámicas , Análisis de SupervivenciaRESUMEN
Eight (0.59%) of 1,347 patients who underwent liver transplantation at the UCLA Medical Center (Los Angeles) developed coccidioidomycosis. Whereas only one case occurred during the first 8 years and 10 months of the UCLA Liver Transplant Program (February 1984 to December 1992), seven cases occurred within the following 23-month period (December 1992 to November 1994). The median time of onset for infection after transplantation was 8 weeks (range, 4-312 weeks). Clinical presentations of patients with coccidioidomycosis included pneumonia (six cases), pneumonia with meningitis (one case), hepatitis (one case), and monoarticular arthritis (one case). Despite therapy with amphotericin B alone (six cases) or amphotericin B plus fluconazole (two cases), infection was fatal in four of eight cases. As of this writing, the four surviving patients are receiving chronic maintenance therapy with either fluconazole (three patients) or itraconazole (one patient). These experiences show that coccidioidomycosis can be a serious and frequently fatal infection after liver transplantation and that the incidence of this disease appears to be increasing.