RESUMO
We studied whether the use of sirolimus with reduced-dose tacrolimus, as compared to standard-dose tacrolimus, after liver transplantation is safe, tolerated and efficacious. In an international multicenter, open-label, active-controlled randomized trial (2000-2003), adult primary liver transplant recipients (n=222) were randomly assigned immediately after transplantation to conventional-dose tacrolimus (trough: 7-15 ng/mL) or sirolimus (loading dose: 15 mg, initial dose: 5 mg titrated to a trough of 4-11 ng/mL) and reduced-dose tacrolimus (trough: 3-7 ng/mL). The study was terminated after 21 months due to imbalance in adverse events. The 24-month cumulative incidence of graft loss (26.4% vs. 12.5%, p=0.009) and patient death (20% vs. 8%, p=0.010) was higher in subjects receiving sirolimus. A numerically higher rate of hepatic artery thrombosis/portal vein thrombosis was observed in the sirolimus arm (8% vs. 3%, p=0.065). The incidence of sepsis was higher in the sirolimus arm (20.4% vs. 7.2%, p=0.006). Rates of acute cellular rejection were similar between the two groups. Early use of sirolimus using a loading dose followed by maintenance doses and reduced-dose tacrolimus in de novo liver transplant recipients is associated with higher rates of graft loss, death and sepsis when compared to the use of conventional-dose tacrolimus alone.
Assuntos
Rejeição de Enxerto/tratamento farmacológico , Sobrevivência de Enxerto/efeitos dos fármacos , Imunossupressores/uso terapêutico , Hepatopatias/cirurgia , Transplante de Fígado , Sirolimo/uso terapêutico , Tacrolimo/uso terapêutico , Adulto , Relação Dose-Resposta a Droga , Feminino , Seguimentos , Rejeição de Enxerto/etiologia , Rejeição de Enxerto/mortalidade , Humanos , Agências Internacionais , Hepatopatias/complicações , Hepatopatias/mortalidade , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Taxa de Sobrevida , Fatores de Tempo , Imunologia de TransplantesRESUMO
A large prospective, open-label, randomized trial evaluated conversion from calcineurin inhibitor (CNI)- to sirolimus (SRL)-based immunosuppression for preservation of renal function in liver transplantation patients. Eligible patients received liver allografts 6-144 months previously and maintenance immunosuppression with CNI (cyclosporine or tacrolimus) since early posttransplantation. In total, 607 patients were randomized (2:1) to abrupt conversion (<24 h) from CNI to SRL (n = 393) or CNI continuation for up to 6 years (n = 214). Between-group changes in baseline-adjusted mean Cockcroft-Gault GFR at month 12 (primary efficacy end point) were not significant. The primary safety end point, noninferiority of cumulative rate of graft loss or death at 12 months, was not met (6.6% vs. 5.6% in the SRL and CNI groups, respectively). Rates of death at 12 months were not significantly different, and no true graft losses (e.g. liver transplantation) were observed during the 12-month period. At 52 weeks, SRL conversion was associated with higher rates of biopsy-confirmed acute rejection (p = 0.02) and discontinuations (p < 0.001), primarily for adverse events. Adverse events were consistent with known safety profiles. In conclusion, liver transplantation patients showed no demonstrable benefit 1 year after conversion from CNI- to SRL-based immunosuppression.
Assuntos
Inibidores de Calcineurina , Rejeição de Enxerto/prevenção & controle , Sobrevivência de Enxerto/efeitos dos fármacos , Imunossupressores/administração & dosagem , Transplante de Fígado , Sirolimo/administração & dosagem , Adolescente , Adulto , Idoso , Ciclosporina/administração & dosagem , Feminino , Taxa de Filtração Glomerular , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Tacrolimo/administração & dosagem , Resultado do TratamentoRESUMO
6-mercaptopurine (6-MP) and azathioprine (AZA) are used to treat inflammatory bowel disease (IBD). Side effects include infection, leukopenia, hepatitis, and pancreatitis. The level of thiopurine methyltransferase (TPMT), which metabolizes 6-MP to 6-methylmercaptopurine, may reflect the risk of side effects. We sought to evaluate the relationship between the side effects of these medications and the TPMT level of pediatric patients with IBD. The medical records of our patients who were diagnosed with IBD and who received 6-MP or AZA were reviewed for measured TPMT levels. All red blood cell (RBC) TPMT levels were determined at the Mayo Medical Laboratories, Rochester, MN. The occurrence of leukopenia, elevated aminotransferases, and pancreatitis was evaluated. Twenty-two patients, mean age 13.7 years, received 6-MP or AZA and had TPMT levels measured. The TPMT levels ranged 10.7-27.5 U/mL RBC with a mean of 17.2 +/- 3.2 U/mL RBC. Two children had levels below the accepted norm of 13.8 U/mL RBC. One of these patients (50%) developed both elevation of aminotransferases and leukopenia. Of all, 20 children had normal levels, 3 (15.0%) exhibited side effects: hepatitis (n = 2) and leukopenia (n = 1). We conclude that side effects of 6-MP or AZA occur despite normal TPMT levels.
Assuntos
Azatioprina/efeitos adversos , Colite Ulcerativa/tratamento farmacológico , Doença de Crohn/tratamento farmacológico , Imunossupressores/efeitos adversos , Mercaptopurina/efeitos adversos , Metiltransferases/sangue , Adolescente , Azatioprina/uso terapêutico , Feminino , Humanos , Imunossupressores/uso terapêutico , Masculino , Mercaptopurina/uso terapêuticoRESUMO
Numerous adult studies show a 30-65% response rate to azathioprine (AZA) or 6-mercaptopurine (6-MP) for significant perianal Crohn's disease. The aim of this study was to evaluate whether these drugs healed pediatric perianal Crohn's disease. Records of pediatric Crohn's patients were retrospectively reviewed for significant perianal disease treated with AZA or 6-MP for > or =6 months. The patient's perianal disease was reviewed and evaluated for fistulas, drainage, induration, and tenderness. In addition, the patients were given a score using the Irvine Perianal Disease Activity Index (PDAI). Patients were retrospectively scored upon initiation of treatment and after six months of therapy. Possible scores ranged from 0-20. Twenty patients met the study criteria. Five patients were considered treatment failures. One patient required a colostomy after 1.5 months of therapy, one developed pancreatitis, and three were noncompliant with therapy. Of the remaining 15 patients who were treated for > or =6 months, 67% had an improvement in drainage, 73% in tenderness, 60% in induration, and 40% in fistula closure. The mean Irvine PDAI was 7.67 +/- 2.19 initially and 4.40 +/- 1.72 after six months of therapy. The improvement was statistically significant (p < 0.001). AZA and 6-MP are effective treatments for healing significant perianal Crohn's disease in pediatrics.
Assuntos
Doenças do Ânus/tratamento farmacológico , Azatioprina/administração & dosagem , Doença de Crohn/tratamento farmacológico , Imunossupressores/administração & dosagem , Mercaptopurina/administração & dosagem , Adolescente , Doenças do Ânus/diagnóstico , Distribuição de Qui-Quadrado , Criança , Pré-Escolar , Doença de Crohn/diagnóstico , Quimioterapia Combinada , Feminino , Seguimentos , Humanos , Masculino , Sistema de Registros , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND: Reconstruction of the hepatic artery in infants undergoing liver transplantation presents challenging vascular situations. Microvascular techniques ensure arterial blood flow via small caliber vessels but are insufficient when inflow is poor. In these situations, the use of allogeneic grafts to the supraceliac aorta have been advocated. The development of a pseudoaneurysm at the supraceliac aortic suture line requires urgent repair and restoration of arterial flow to the graft. METHODS: Our study was based on case reports and review of the literature. RESULTS: Definitive diagnosis and successful repair of supraceliac pseudoaneurysm was accomplished in two infants after transplantation. CONCLUSION: We advocate a thoracoabdominal retroperitoneal approach, which provides safe control of the aorta and primary repair or patching of the diseased aortic segment, and also provides access for hepatic revascularization via placement of an infrarenal graft. Thrombosis of the artery and subsequent liver necrosis are indications for retransplantation.
Assuntos
Falso Aneurisma/etiologia , Aneurisma da Aorta Abdominal/etiologia , Transplante de Fígado/métodos , Falso Aneurisma/diagnóstico , Falso Aneurisma/cirurgia , Aneurisma da Aorta Abdominal/diagnóstico , Aneurisma da Aorta Abdominal/cirurgia , Atresia Biliar/cirurgia , Feminino , Artéria Hepática/cirurgia , Humanos , Lactente , Complicações Pós-Operatórias , Reoperação , Resultado do TratamentoRESUMO
The liver transplant program at the University of Pennsylvania and the Children's Hospital of Philadelphia experienced healthy growth in its clinical activity in the past 5 years. Patterns of referral and patient evaluation were established, care of patients while waiting on the list or being followed after transplantation was streamlined. We are now achieving excellent outcomes while transplanting relatively sicker patients. Innovative surgical procedures are implemented resulting in more efficient utilization of cadaveric and living-donor liver grafts. The protocols that are used for patient care are more standard, yet flexible and accommodate recent advancement in transplantation immunobiology. This progress of the clinical program was enhanced by careful preservation of the academic mission of the institution, which encourages the liver transplant faculty to be involved in NIH-supported clinical and basic science research.
Assuntos
Transplante de Fígado/estatística & dados numéricos , Adulto , Cadáver , Criança , Sobrevivência de Enxerto , Hospitais Pediátricos , Hospitais Universitários , Humanos , Hepatopatias/classificação , Hepatopatias/cirurgia , Transplante de Fígado/mortalidade , Transplante de Fígado/fisiologia , Doadores Vivos , Philadelphia , Reoperação/estatística & dados numéricos , Estudos Retrospectivos , Taxa de Sobrevida , Doadores de Tecidos/provisão & distribuição , Obtenção de Tecidos e Órgãos/organização & administração , Listas de EsperaRESUMO
BACKGROUND & AIMS: Clostridium difficile is an important cause of symptomatic diarrhea in pediatric patients. The bacterium produces two toxins, although many laboratories assay for only one. We questioned this diagnostic approach when patients had positive results for C. difficile at our institution, but initially had tested negative at outside laboratories. METHODS: We retrospectively analyzed relative frequencies of C. difficile toxin A alone, toxin B alone, and toxins A and B from pediatric patients with diarrhea. Results were stratified according to toxin detection and patient age. RESULTS: Of 1061 specimens, 276 (26.8%) were positive for C. difficile toxin(s). Fifty-one (18.5%) were positive for toxin A alone, 133 (48.2%) for toxin B alone, and 92 (33.3%) for both toxins. Assaying for toxin B identified C. difficile infection more frequently than did assaying for toxin A (P < 0.0001). The frequency of toxin B detection was significantly higher for older children but not for infants. CONCLUSIONS: Testing for C. difficile toxin A or toxin B alone will result in more frequent misdiagnosis than testing for both toxins. This practice may lead to inappropriate further invasive investigations in children, although this finding may not be applicable to adults.
Assuntos
Toxinas Bacterianas , Clostridioides difficile , Infecções por Clostridium/diagnóstico , Diarreia/diagnóstico , Diarreia/microbiologia , Adolescente , Criança , Pré-Escolar , Humanos , Lactente , Estudos Retrospectivos , Sensibilidade e EspecificidadeAssuntos
Constipação Intestinal/terapia , Síndrome de Ehlers-Danlos/complicações , Enema/efeitos adversos , Perfuração Intestinal/etiologia , Abdome Agudo/etiologia , Adolescente , Constipação Intestinal/complicações , Síndrome de Ehlers-Danlos/patologia , Evolução Fatal , Feminino , Humanos , Perfuração Intestinal/cirurgia , MasculinoAssuntos
Doenças do Ânus/diagnóstico , Encoprese/etiologia , Histiocitose de Células de Langerhans/diagnóstico , Obstrução Intestinal/etiologia , Doenças do Ânus/complicações , Doenças do Ânus/tratamento farmacológico , Pré-Escolar , Histiocitose de Células de Langerhans/complicações , Histiocitose de Células de Langerhans/tratamento farmacológico , Humanos , Masculino , Metotrexato/uso terapêutico , Prednisona/uso terapêuticoAssuntos
Rejeição de Enxerto/epidemiologia , Transplante de Fígado , Doença Aguda , Criança , Doença Crônica , Ciclosporina/uso terapêutico , Seguimentos , Rejeição de Enxerto/tratamento farmacológico , Humanos , Imunossupressores/uso terapêutico , Incidência , Transplante de Fígado/imunologia , Transplante de Fígado/fisiologia , Muromonab-CD3/uso terapêutico , Estudos Retrospectivos , Tacrolimo/uso terapêutico , Fatores de Tempo , Recusa do Paciente ao TratamentoRESUMO
Uncut Collis-Nissen fundoplication for complicated gastroesophageal reflux was performed in 102 children (46 girls; age 5.6 +/- 4.2 years). Five patients developed intractable emesis postoperatively (average 11 +/- 5 months after surgery) and were found to have two independent luminal openings at the gastroesophageal junction seen on upper endoscopy but not demonstrable on upper GI. The defect was presumed to occur from breakdown of the original staple line on the lesser gastric curve. The condition was successfully repaired in all patients by including a new staple line and rewrapping of the stomach. Practitioners should be aware of this previously unreported complication post uncut Collis-Nissen fundoplication and that this condition may not be excluded by a normal upper GI study.
Assuntos
Fundoplicatura/efeitos adversos , Refluxo Gastroesofágico/cirurgia , Grampeamento Cirúrgico/efeitos adversos , Criança , Pré-Escolar , Feminino , Fundoplicatura/métodos , Gastroscopia , Humanos , Masculino , Complicações Pós-Operatórias/cirurgia , Vômito/etiologiaRESUMO
Inflammatory myofibroblastic tumor is a rare gastrointestinal neoplasm. The authors report the case of a 5-year-old girl who initially presented with gastric outlet obstruction secondary to an inflammatory myofibroblastic tumor along the lesser gastric curvature. A subtotal gastrectomy and wedge resection of a left hepatic lobe nodule were performed. Obstructive jaundice developed one month postoperatively. Computerized tomography, percutaneous transhepatic cholangiography, and selective celiac and mesenteric arteriography showed a mass that involved the left hepatic lobe, with concomitant high-grade biliary obstruction and portal venous encasement. Percutaneous biliary drainage was performed. During laparotomy, the tumor was found to be unresectable, and the patient was referred to the Liver Transplant Service at The Children's Hospital of Philadelphia. A total hepatectomy with temporary portocaval shunt was performed, leaving the inferior vena cava in situ. At the back table, an ex vivo left trisegmentectomy was performed, followed by reimplantation of the posterior segment of the right hepatic lobe. The reimplanted liver segment functioned poorly, and completion hepatectomy with portocaval shunt was performed 24 hours postoperatively, because of severe coagulopathy, intraabdominal bleeding, and hemodynamic instability. The patient's condition stabilized, and she was listed for urgent liver transplantation. The anhepatic state was managed with intermittent plasmapheresis. She had transplantation 72 hours later, and was discharged from the hospital 3 weeks postoperatively after an uneventful recovery. She remains disease-free and has normal liver function 8 months after transplantation.
Assuntos
Neoplasias Hepáticas/cirurgia , Transplante de Fígado/métodos , Recidiva Local de Neoplasia/cirurgia , Neoplasias de Tecido Muscular/cirurgia , Neoplasias Gástricas/patologia , Pré-Escolar , Feminino , Humanos , Inflamação , Neoplasias Hepáticas/secundário , Neoplasias de Tecido Muscular/secundário , Plasmaferese , Reoperação , Neoplasias Gástricas/cirurgiaAssuntos
Infecções por Echovirus/cirurgia , Doenças do Prematuro/cirurgia , Falência Hepática/cirurgia , Transplante de Fígado , Infecções por Echovirus/congênito , Infecções por Echovirus/diagnóstico , Feminino , Seguimentos , Rejeição de Enxerto/prevenção & controle , Humanos , Terapia de Imunossupressão/métodos , Recém-Nascido , Doenças do Prematuro/diagnóstico , Injeções Intravenosas , Fígado/patologia , Falência Hepática/congênito , Falência Hepática/diagnóstico , Muromonab-CD3/administração & dosagem , Muromonab-CD3/uso terapêutico , Complicações Pós-Operatórias , Resultado do TratamentoAssuntos
Hemocromatose/complicações , Falência Hepática/cirurgia , Transplante de Fígado/métodos , Fatores de Coagulação Sanguínea/análise , Ciclosporina/uso terapêutico , Transfusão Total , Feminino , Hemocromatose/sangue , Humanos , Terapia de Imunossupressão/métodos , Recém-Nascido , Falência Hepática/etiologia , Transplante de Fígado/fisiologia , Masculino , Metilprednisolona/uso terapêutico , Prednisona/uso terapêuticoRESUMO
Cholestasis develops in many infants supported with extracorporeal membrane oxygenation. We prospectively investigated the role of hemolysis and di-(2-ethylhexyl) phthalate exposure in the development of this cholestasis. Both di-(2-ethylhexyl) phthalate levels and hemolysis, as measured by maximum free hemoglobin, were significantly (p less than 0.025) associated with the degree of cholestasis. Other clinical and laboratory factors that may contribute to cholestasis were also investigated and not found to be related to the degree of cholestasis. We speculate that hemolysis during extracorporeal membrane oxygenation support produces a large bilirubin load whose excretion is inhibited by mechanisms similar to the inspissated bile syndrome and/or by di-(2-ethylhexyl) phthalate. This would result in a predominantly direct hyperbilirubinemia with little evidence of hepatocellular or canalicular injury.