RESUMEN
OBJECTIVE: To compare portal and systemic venous drainage of pancreas transplants and demonstrate an immunologic and survival superiority of portal venous drainage. SUMMARY BACKGROUND DATA: Traditionally, solitary pancreas transplants have been performed using systemic venous and bladder drainage, but more recently, the advantages of enteric drainage have been well documented. Although physiologic benefits for portal venous drainage have been described, the impact of portal venous drainage, especially with solitary pancreas transplants, has yet to be determined. METHODS: Since August 1995, 280 pancreas transplants with enteric duct drainage were analyzed. One hundred and seventeen were simultaneous pancreas and kidney (SPK), 63 with systemic venous drainage (SV) and 54 with portal venous drainage (PV). The remainder were solitary transplants; 97 pancreas after kidney (PAK; 42 SV and 55 PV) and 66 transplants alone (PTA; 26 SV and 40 PV). Immunosuppressive therapy was equivalent for both groups. RESULTS: The groups were similar with respect to recipient characteristics and HLA matching. Thirty-six month graft survival for all transplants was 79% for PV and 65% for SV (P =.008). By category, SPK graft survival was 74% for PV and 76% for SV, PAK graft survival was 70% for PV and 56% for SV, and PTA graft survival was 84% for PV and 50% for SV. The rate of at least one rejection episode was also significantly higher in the SV group. At 36 months, for all pancreas transplants, the rejection rate was 21% for PV and 52% for SV (P <.0001). For SPK, rejection rates were 9% for PV and 45% for SV. For PAK, rejection rates were 16% for PV and 65% for SV, and for PTA 36% for PV and 51% for SV. The rejection rates for kidneys following SPK were also lower in the PV group (26% versus 43% for SV). Furthermore, the grades of rejection were milder in PV for all transplants (P =.017). By multivariate analysis, portal venous drainage was the only parameter that significantly affected rejection. CONCLUSION: Graft survival and rejection is superior for PV. These clinical findings are consistent with published reports of experimentally induced portal tolerance and strongly argue that PV drainage should be the procedure of choice for pancreas transplantation.
Asunto(s)
Trasplante de Páncreas/métodos , Vena Porta/cirugía , Adulto , Anastomosis en-Y de Roux , Anastomosis Quirúrgica , Diabetes Mellitus Tipo 1/cirugía , Duodeno/cirugía , Femenino , Supervivencia de Injerto , Humanos , Vena Ilíaca/cirugía , Inmunosupresores/uso terapéutico , Yeyuno/cirugía , Trasplante de Riñón/métodos , Masculino , Estudios RetrospectivosRESUMEN
CD80 and CD86 (also known as B7-1 and B7-2, respectively) are both ligands for the T cell costimulatory receptors CD28 and CD152. Both CD80 and CD86 mediate T cell costimulation, and as such, have been studied for their role in promoting allograft rejection. In this study we demonstrate that administering monoclonal antibodies specific for these B7 ligands can delay the onset of acute renal allograft rejection in rhesus monkeys. The most durable effect results from simultaneous administration of both anti-B7 antibodies. The mechanism of action does not involve global depletion of T or B cells. Despite in vitro and in vivo evidence demonstrating the effectiveness of the anti-B7 antibodies in suppressing T cell responsiveness to alloantigen, their use does not result in durable tolerance. Prolonged therapy with murine anti-B7 antibodies is limited by the development of neutralizing antibodies, but that problem was avoided when humanized anti-B7 reagents are used. Most animals develop rejection and an alloantibody response although still on antibody therapy and before the development of a neutralizing antibody response. Anti-B7 antibody therapy may have use as an adjunctive agent for clinical allotransplantation, but using the dosing regimens we used, is not a tolerizing therapy in this non-human primate model.
Asunto(s)
Anticuerpos Monoclonales/inmunología , Anticuerpos Monoclonales/uso terapéutico , Antígenos CD/inmunología , Antígeno B7-1/inmunología , Rechazo de Injerto/prevención & control , Trasplante de Riñón , Glicoproteínas de Membrana/inmunología , Enfermedad Aguda , Animales , Formación de Anticuerpos/efectos de los fármacos , Antígeno B7-2 , Células Dendríticas/patología , Quimioterapia Combinada , Rechazo de Injerto/genética , Humanos , Riñón/patología , Prueba de Cultivo Mixto de Linfocitos , Linfocitos/patología , Macaca mulatta , ARN/análisis , Seguridad , Donantes de Tejidos , Trasplante HomólogoRESUMEN
We report a case of a 62-yr-old man with chronic hepatitis B virus (HBV)-related cirrhosis who developed hepatic decompensation after being started on lamivudine requiring liver transplantation. Decompensated liver disease while on lamivudine has been previously reported on two occasions, both HIV coinfected patients on a combination of nucleoside analogues. Our patient is alive and well nearly 2 yr after successful liver transplantation.
Asunto(s)
Lamivudine/efectos adversos , Fallo Hepático/inducido químicamente , Hígado/efectos de los fármacos , Inhibidores de la Transcriptasa Inversa/efectos adversos , Hepatitis B Crónica/tratamiento farmacológico , Humanos , Lamivudine/uso terapéutico , Hígado/patología , Fallo Hepático/patología , Fallo Hepático/cirugía , Trasplante de Hígado , Masculino , Persona de Mediana Edad , Inhibidores de la Transcriptasa Inversa/uso terapéuticoAsunto(s)
Suero Antilinfocítico/administración & dosificación , Inmunosupresores/administración & dosificación , Trasplante de Riñón/inmunología , Trasplante de Páncreas/inmunología , Terapia Combinada , Glucocorticoides/administración & dosificación , Humanos , Infusiones Intravenosas , Metilprednisolona/administración & dosificación , Inducción de RemisiónRESUMEN
The evolution of enteric and portal venous drainage, better immunosuppression, and better patient care has elevated pancreas transplantation with dramatically improved results. At our center, long-term graft survival and rejection has significantly improved with portal venous drainage, which has become our gold standard. This improvement is exemplified by the excellent one-year patient and graft survival rates for SPLK transplants. SPLK has proven to be an ideal approach in uremic Type 1 diabetic patients with living donors and should become the procedure of choice for that population. Moreover, the improved monitoring of rejection has allowed a similar success of pancreas transplantation alone in non-uremic patients with brittle diabetes. The treatment of diabetes mellitus has room for great improvement, however, and there is no question that islet transplantation, xenotransplantation, and the pursuit of immunologic tolerance will play an extremely important role in that endeavor.
Asunto(s)
Trasplante de Riñón/métodos , Trasplante de Páncreas/métodos , Centros Médicos Académicos , Cadáver , Rechazo de Injerto/diagnóstico , Supervivencia de Injerto , Humanos , Terapia de Inmunosupresión , Trasplante de Riñón/estadística & datos numéricos , Laparoscopía , Donadores Vivos , Maryland , Nefrectomía/métodos , Trasplante de Páncreas/estadística & datos numéricos , Selección de Paciente , Vena Porta/cirugía , Cuidados Posoperatorios , Obtención de Tejidos y Órganos/métodosRESUMEN
BACKGROUND: This study examines the current cost of live donor (LD) transplantation at our institution, and compares it with that of dialysis. METHODS: The study population consisted of 184 consecutive adult recipients of laparoscopically procured LD kidney transplants. Cost-containment measures instituted during this series included elimination of routine postoperative antilymphocyte induction and an accelerated discharge clinical pathway with planned discharge of the recipient on postoperative day (POD) 2. Costs of the transplants to Medicare were estimated from hospital charges, readmission rates, and immunosuppressant usage. These were compared with published costs of dialysis to Medicare in terms of a fiscal transplant-dialysis break-even point. RESULTS: Kaplan-Meier patient and graft survival rates at 1 year were 97 and 93%, respectively. Among patients followed for at least 90 days and treated with no induction and either cyclosporine-mycophenolate mofetil or tacrolimus-mycophenolate mofetil, acute rejection rates were low (27.6 and 13.9%, respectively). In the last 124 patients, 32.3% were discharged by POD 3 and 71.8% by POD 6, with corresponding mean transplant hospital charges (excluding organ acquisition) of $11,873 and $17,350, respectively. The 30-day readmission rate for patients discharged on the accelerated pathway by POD 3 was only 16%. The least expensive subgroup in the present study (30% of patients) was that of patients discharged by POD 6 and not readmitted during the first year; the break-even point with dialysis costs was calculated as 1.7 years after the transplant. CONCLUSIONS: The cost of LD transplants can be safely reduced by elimination of routine postoperative anti-lymphocyte immune induction and by an early discharge clinical pathway. Uncomplicated LD kidney transplants, meaning those with a short length of stay in the hospital after transplantation and no need for readmission within the first year, accrue savings over dialysis within 2 years.
Asunto(s)
Trasplante de Riñón/economía , Adolescente , Adulto , Anciano , Femenino , Rechazo de Injerto , Precios de Hospital , Humanos , Tiempo de Internación , Masculino , Medicare , Persona de Mediana Edad , Readmisión del Paciente , Diálisis Renal , Estados UnidosRESUMEN
1. The number of kidney transplants performed at the University of Maryland increased yearly from 51 in 1991 to 285 in 1998. Over the past 3 years, the increase in the number of kidney transplants can be ascribed almost exclusively to a marked increase in living donor transplants, from 49 cases in 1995 to 130 cases in 1998; a 160% increase. The increase in our frequency of living-donor kidney transplantation can be attributed to a formal family education program and the availability of the laparoscopic technique for kidney removal. 2. In addition to the availability of the laparoscopic technique, a number of special programs has allowed an increased number of living donor kidney transplants. This includes a special protocol for transplantation of Epstein-Barr virus negative recipients, a protocol for transplantation of patients who have a positive crossmatch with a living donor, as well as, the simultaneous living donor kidney/cadaver pancreas "SPK(LRD/PTA)" program. 3. The one-year graft and patient survival for the entire program was 87.0% and 94.5%, respectively. However, the more recent graft survival rates have markedly increased; Since August 1995, the one-year graft and patient survival was 89.8% and 95.8%, respectively. 4. Improvement in immunosuppression has lead to dramatic improvement in the success rates in living-donor kidney transplants. Despite the omission of antibody-based induction therapy, the one-year graft survival rate using a mycophenolate mofetil/tacrolimus-based immunosuppression protocol was 96.4%. The one-year rejection rate was 8% in Caucasian patients and 14% in African-American patients in this subgroup of living-donor kidney transplant recipients. 5. The data demonstrate that the use of the living-donor transplant option is grossly underutilized. Estimates are presented that more than 11,000 living-donor kidney transplants should be possible in the US yearly.
Asunto(s)
Trasplante de Riñón/estadística & datos numéricos , Población Negra , Femenino , Supervivencia de Injerto , Hospitales Universitarios/estadística & datos numéricos , Humanos , Inmunosupresores/uso terapéutico , Fallo Renal Crónico/cirugía , Trasplante de Riñón/mortalidad , Trasplante de Riñón/fisiología , Laparoscopía/métodos , Donadores Vivos/estadística & datos numéricos , Masculino , Maryland , Nefrectomía/métodos , Reoperación , Estudios Retrospectivos , Tasa de Supervivencia , Donantes de Tejidos/estadística & datos numéricos , Recolección de Tejidos y Órganos/métodos , Población BlancaAsunto(s)
Trasplante de Riñón/fisiología , Riñón , Soluciones Preservantes de Órganos , Preservación de Órganos/métodos , Donantes de Tejidos , Adenosina , Adolescente , Adulto , Anciano , Alopurinol , Niño , Femenino , Glutatión , Humanos , Insulina , Masculino , Persona de Mediana Edad , Rafinosa , Factores de TiempoAsunto(s)
Intestino Delgado/trasplante , Trasplante de Hígado , Trasplante Homólogo/métodos , Sistema del Grupo Sanguíneo ABO , Adulto , Niño , Rechazo de Injerto/epidemiología , Prueba de Histocompatibilidad , Hospitales Universitarios , Humanos , Los Angeles , Complicaciones Posoperatorias , Reoperación , Estudios Retrospectivos , Trasplante Homólogo/inmunología , Trasplante Homólogo/patologíaRESUMEN
This is a case report of a primary vena cava sarcoma extending to the atrium in a young woman, which was resected. Cardiopulmonary bypass was used, and the cava replaced with ringed Gore-Tex. She remains alive and well more than 3 years after the surgery with no evidence of recurrence.
Asunto(s)
Prótesis Vascular , Neoplasias Cardíacas/cirugía , Leiomiosarcoma/cirugía , Neoplasias Vasculares/cirugía , Vena Cava Inferior/cirugía , Adulto , Femenino , Estudios de Seguimiento , Paro Cardíaco Inducido , Atrios Cardíacos , Neoplasias Cardíacas/patología , Humanos , Leiomiosarcoma/patología , Invasividad Neoplásica , Sobrevivientes , Neoplasias Vasculares/patologíaAsunto(s)
Factor Estimulante de Colonias de Granulocitos/uso terapéutico , Trasplante de Hígado/inmunología , Neutropenia/tratamiento farmacológico , Adulto , Anciano , Femenino , Rechazo de Injerto/prevención & control , Factor Estimulante de Colonias de Granulocitos/administración & dosificación , Humanos , Recuento de Leucocitos , Trasplante de Hígado/efectos adversos , Masculino , Persona de Mediana Edad , Neutropenia/sangre , Neutropenia/etiologíaRESUMEN
Between February 1984 and July 1992, six adults with advanced pancreatic adenocarcinoma (n = 1), pancreatic neuroendocrine tumor (n = 2), and cholangiocarcinoma (n = 3) underwent radical foregut resections (n = 3) or radical pancreaticoduodenectomy (n = 3) combined with liver transplantation. The major postoperative complications included diarrhea (n = 4), pancreaticojejunostomy leak (n = 3), infection (n = 7), malnutrition (n = 3), refractory ascites (n = 2), and late hepatic artery thrombosis (n = 1). Tumor recurrence occurred in one patient. The actuarial survival for the group is 82 per cent at 1 year and 55 per cent at 2 years. The results demonstrate that radical pancreaticoduodenectomy/foregut resections combined with liver transplantation offer potential surgical cure of malignancies involving these organs. However, the procedure is formidable, with frequent complications.
Asunto(s)
Neoplasias de los Conductos Biliares/cirugía , Neoplasias Hepáticas/cirugía , Trasplante de Hígado , Neoplasias Pancreáticas/cirugía , Adenocarcinoma/mortalidad , Adenocarcinoma/patología , Adenocarcinoma/cirugía , Adulto , Neoplasias de los Conductos Biliares/mortalidad , Neoplasias de los Conductos Biliares/patología , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/cirugía , Carcinoma Neuroendocrino/mortalidad , Carcinoma Neuroendocrino/patología , Carcinoma Neuroendocrino/cirugía , Colangiocarcinoma/mortalidad , Colangiocarcinoma/patología , Colangiocarcinoma/cirugía , Terapia Combinada , Femenino , Supervivencia de Injerto , Hepatoblastoma/mortalidad , Hepatoblastoma/patología , Hepatoblastoma/cirugía , Humanos , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Neoplasias Pancreáticas/mortalidad , Neoplasias Pancreáticas/patología , Complicaciones Posoperatorias/epidemiología , Estudios Retrospectivos , Tasa de Supervivencia , Factores de TiempoRESUMEN
In this randomized controlled trial comparing FK-506 to CsA, we report parameters of nephrotoxicity in adult patients surviving > 90 days after orthotopic liver transplant (OLT). Patients randomized to FK-506 first received 0.15 mg/kg IV/day followed by 0.3 mg/kg PO/day. Doses were modified to avoid toxicity and to achieve FK-506 levels of 0.5 to 1.5 ng/ml. CsA was administered in the usual manner with dose adjustments to whole blood HPLC levels. A pre-OLT glomerular filtration rate (GFR) of > or = 30 ml/min/1.73/m2 and/or serum creatinine < or = 2.0 mg/dl were required for inclusion in the study. GFRs were obtained at post OLT days 28, 180, and 360. Other parameters of renal function evaluated were creatinine, magnesium, serum electrolytes, blood pressure, use of antihypertensives, and magnesium supplements. There were 38 patients in the FK-506 group and 34 in the CsA group. The mean days of follow up for each group was similar: 456 +/- 135 days for the FK-506 group and 451 +/- 112 days for the CsA group. The mean oral dose for the FK-506 group ranged from 0.13-0.16 mg/kg/day with mean FK-506 levels of 0.6-0.8 ng/ml. In the FK-506 group, there was a significant fall in the pre-transplant GFR from 89 +/- 31 ml/min/173 m2 to 43 +/- 15 ml/min/173 m2 at day 360. Similarly, for the CsA group, the pre-transplant GFR of 75 +/- 31 ml/min/1.73 m2 fell to 49 +/- 17 ml/min/1.73 m2 at day 360. At each time point studied, there was no significant difference in mean GFR between the two groups. There were no significant differences in the monthly mean values for creatinine, electrolytes, magnesium, or blood pressure between the two groups. Magnesium levels were in the low normal range (1.4-1.6 mEq/L), and the mean potassium levels in the high normal range (4.4-4.7 mEq/L). In both groups, a similar number of patients required magnesium supplementation or hypertensive medications. The nephrotoxicity of FK-506 given at low oral doses and with concomitant low levels was comparable to that of CsA. The two drugs were remarkably similar in their spectrum of electrolyte disturbances and incidence of hypertension.
Asunto(s)
Ciclosporina/uso terapéutico , Tasa de Filtración Glomerular/efectos de los fármacos , Riñón/efectos de los fármacos , Trasplante de Hígado/fisiología , Tacrolimus/uso terapéutico , Adulto , Presión Sanguínea/efectos de los fármacos , Creatinina/sangre , Electrólitos/sangre , Estudios de Seguimiento , Humanos , Riñón/fisiología , Trasplante de Hígado/inmunología , Magnesio/sangre , Metilprednisolona/uso terapéutico , Potasio/sangre , Factores de TiempoRESUMEN
The oral dose recommendation for FK506 (Fujisawa Pharmaceutical, Deerfield, IL) after liver transplantation has, to date, made no distinction between adult and pediatric patients. Sixteen pediatric and 33 adult liver transplant patients treated long term with oral FK506 were studied. Initial FK506 doses were 0.3 mg/kg/day p.o. or 0.15 mg/kg/day i.v. Thereafter, doses were adjusted to achieve therapeutic FK506 serum levels (0.5-3.0 ng/ml, ELISA liquid/liquid separation) and to maintain an acceptable serum creatinine. FK506 (in mg/kg/day), FK506 levels, and liver function were assessed at monthly intervals on outpatient visits. The mean age of 16 pediatric patients was 5.3 +/- 3.5 years and of 33 adult patients was 49 +/- 12 years. Mean days of FK506 therapy were 284 +/- 136 for pediatric patients and 239 +/- 112 for adult patients. For each time period, pediatric patients required a significantly higher dose of FK506 compared to adult patients (P < 0.001). The overall mean pediatric dose for the first year was 0.46 +/- 0.4 mg/kg/day compared to the mean adult dose of 0.13 +/- 0.01 mg/kg/day. The ratio of pediatric to adult oral FK506 dose requirements ranged from 2.7 to 4.4 over the 1 year of followup. FK506 levels monitored at the same time points showed no significant differences at any month between pediatric and adult patients. We conclude that the oral dose per kilogram per day of FK506 required to maintain similar FK506 levels is significantly greater in pediatric patients compared to adult recipients during the first year of follow-up. Pediatric recipients require substantially more, and adult recipients substantially less, than the recommended oral FK506 dose to achieve a therapeutic effect.
Asunto(s)
Trasplante de Hígado/métodos , Tacrolimus/administración & dosificación , Administración Oral , Adulto , Niño , Preescolar , Diarrea/complicaciones , Interacciones Farmacológicas , Rechazo de Injerto , Humanos , Terapia de Inmunosupresión/métodos , Persona de Mediana Edad , Rifampin/administración & dosificaciónRESUMEN
Isolated resection of the caudate lobe for primary or metastatic neoplasms is an uncommon operation. Our experience with mobilization of the liver in more than 700 hepatic transplants has led us to a simplified technique for caudate lobe resection. Herein we describe our technique and report our experience with three patients.
Asunto(s)
Hígado/cirugía , Adulto , Anciano , Femenino , Humanos , Masculino , Procedimientos Quirúrgicos Operativos/métodosRESUMEN
Six hundred sixty-six patients received 792 liver transplants between February 1, 1984 and September 30, 1991. Biliary reconstruction was by choledochocholedochostomy (CDCD) with T-tube (n = 509) or Roux-en-Y choledochojejunostomy (CDJ) (n = 283). Twenty-five patients (4%) developed biliary strictures. Anastomotic strictures were more common after CDJ (n = 10, 3.5%) than for CDCD (n = 3, 0.6%). Intrahepatic strictures developed in 12 patients. Six patients had occult hepatic artery thrombosis (HAT). The other six patients received grafts in which cold ischemia time exceeded 12 hours. Anastomotic strictures were successfully managed by percutaneous dilation (PD) in five patients (n = 10), operation in three (n = 6), with retransplantation required in two patients. Intrahepatic strictures were managed by PD in seven, retransplantation in one, and expectantly in four patients. Of 25 patients, 19 (76%) are alive with good graft function. In three of six deaths, the biliary stricture was a significant factor to the development of sepsis and allograft failure. The authors conclude that (1) anastomotic strictures are rare after LT; (2) the development of biliary strictures may signify occult HAT; (3) PD is effective for most strictures; and (4) extended cold graft ischemia (less than 12 hours) may be injurious to the biliary epithelium, resulting in intrahepatic stricture formation.
Asunto(s)
Colestasis/etiología , Trasplante de Hígado , Complicaciones Posoperatorias , Adulto , Anastomosis en-Y de Roux/efectos adversos , Niño , Coledocostomía , Colestasis/terapia , Colestasis Intrahepática/etiología , Colestasis Intrahepática/terapia , Dilatación , Supervivencia de Injerto , Humanos , Reoperación , Irrigación TerapéuticaRESUMEN
Thirty-six patients underwent orthotopic liver transplantation (OLT) for primary sclerosing cholangitis under cyclosporine, azathioprine, and steroid immunosuppression. Of these patients, 29 suffered from chronic ulcerative colitis. The purpose of this study is to determine (1) whether replacement of the diseased liver and the altered immunocompetence suppresses the manifestation of chronic ulcerative colitis, and (2) if active colonic disease alters allograft function. Thirty of 36 patients survived OLT. After OLT, seven of 14 patients with symptomatic colon disease at the time of transplantation continue to suffer from active chronic ulcerative colitis, and three of 13 who were asymptomatic developed clinically active disease. Intractable colonic disease was the indication for post-OLT proctocolectomy in three patients, and one refused an indicated colectomy. Despite the long duration of the disease, none developed colonic malignancy. Long-term graft assessment showed good hepatocyte synthetic function in patients suffering from either active or inactive disease. Liver alkaline phosphatase, however, was significantly higher in patients suffering from active colonic disease. Furthermore, the alkaline phosphatase in symptomatic patients was higher than that seen in a matched cohort undergoing OLT for chronic active hepatitis or primary biliary cirrhosis. These results suggest that (1) liver replacement and immunosuppression in patients suffering from sclerosing cholangitis and ulcerative colitis do not alter the course of the colon disease, and (2) active chronic ulcerative colitis does not adversely affect allograft function, although elevation of alkaline phosphatase may be the harbinger of recurrence over the long term.
Asunto(s)
Colangitis Esclerosante/complicaciones , Colitis Ulcerosa/complicaciones , Trasplante de Hígado , Adulto , Colangitis Esclerosante/patología , Colangitis Esclerosante/cirugía , Colitis Ulcerosa/fisiopatología , Femenino , Supervivencia de Injerto , Humanos , Hígado/patología , Trasplante de Hígado/mortalidad , Masculino , RecurrenciaRESUMEN
Early hepatic artery thrombosis after orthotopic liver transplantation results in massive injury to hepatocytes and the bile duct epithelium. In the fulminate form, impaired liver synthetic function is expressed by encephalopathy and coagulopathy. Ischemic bile duct injury is associated with the disruption of the biliary anastomosis, bile duct strictures, and intrahepatic bilomas. The inability of the liver macrophages to clear translocated portal blood intestinal pathogens results in persistent bacteremia and sepsis. The major radiologic finding is the radiographic evidence of gas gangrene of the liver graft. Early recognition and correct interpretation of the radiologic findings, immediate removal of the liver graft, and placement of the patient on venous-venous bypass or total hepatic devascularization while a new liver is being procured and retransplantation are the only hope for survival.