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1.
Ann Surg Oncol ; 25(3): 660-666, 2018 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-29285641

RESUMEN

BACKGROUND: Hyperthermic intraperitoneal chemotherapy (HIPEC) following cytoreductive surgery (CRS), performed using closed-abdomen technique (CAT), may affect intraabdominal pressure (IAP). High IAP may increase postoperative complications due to decreased venous return and hypoperfusion to vital organs. Elevated core body temperature (CBT) may cause multiorgan dysfunction. Low IAP or CBT could result in suboptimal HIPEC and potentially translate into early disease recurrence. The aim of the present study is to identify possible correlations between IAP or CBT and postoperative complications. PATIENTS AND METHODS: Continuous intraabdominal pressure measurement was performed by intraabdominal catheter. Inflow temperature was set at 44 °C, and mean perfusate temperature was 42 °C. CBT was measured continuously in the distal esophagus. We compared the rate of postoperative complications between the low IAP group (2-10 mmHg, n = 28), target IAP group (10-20 mmHg, n = 71), and high IAP group (20-34 mmHg, n = 16) as well as with CBT as a continuous variable. RESULTS: 115 patients were included in the study. There was no difference between IAP groups in terms of age, gender, primary diagnosis, operative peritoneal cancer index, CBT, or operative time. There was no correlation between IAP and postoperative complications or with prolonged hospital stay. On multivariate analysis, elevated mean CBT was a positive predictor of postoperative complications (p = 0.035). CONCLUSIONS: IAP level during closed-abdomen technique HIPEC is not associated with postoperative complications. However, elevated CBT may increase postoperative complications.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Temperatura Corporal , Procedimientos Quirúrgicos de Citorreducción/efectos adversos , Hipertermia Inducida/efectos adversos , Hipertensión Intraabdominal/etiología , Neoplasias Peritoneales/terapia , Complicaciones Posoperatorias/diagnóstico , Quimioterapia Adyuvante , Quimioterapia del Cáncer por Perfusión Regional , Terapia Combinada , Femenino , Estudios de Seguimiento , Humanos , Tiempo de Internación , Masculino , Persona de Mediana Edad , Neoplasias Peritoneales/patología , Pronóstico , Estudios Prospectivos , Estudios Retrospectivos
2.
Diabetes Metab Res Rev ; 33(8)2017 11.
Artículo en Inglés | MEDLINE | ID: mdl-28731619

RESUMEN

OBJECTIVE: Clinical outcomes in individuals with new onset diabetes after transplantation (NODAT) and the optimal treatment for this complication are poorly characterized. This study was intended to better define these issues. METHODS: Patients who underwent kidney transplantation and did not have diabetes prior to transplantation were included in the study. Clinical outcomes were compared between those who developed NODAT and those who did not. In those who developed NODAT, oral therapy was compared with insulin based therapy. RESULTS: A total of 266 kidney transplant recipients were included, of which 71 (27%) developed NODAT during the time of the follow-up. Using Cox multivariate analysis adjusted for age and gender, hazard ratio for overall mortality among patients with NODAT versus those without NODAT was 2.69 (95% CI 1.04-7.01). Among patients who developed NODAT, 29 patients (40%) were treated with an insulin-based regimen. At the end of follow-up, no difference was found in mean HbA1c, and therapy regimen was not associated with greater mortality. CONCLUSIONS: New onset diabetes in kidney transplanted patients is associated with increased mortality compared with kidney transplanted patients without NODAT.


Asunto(s)
Diabetes Mellitus/etiología , Diabetes Mellitus/mortalidad , Trasplante de Riñón/efectos adversos , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/mortalidad , Pronóstico , Estudios Retrospectivos , Tasa de Supervivencia
4.
Am J Transplant ; 15(4): 1076-80, 2015 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-25737018

RESUMEN

The Israeli transplantation law of 2008 stipulated that organ trading is a criminal offense, and banned the reimbursement of such transplants by insurance companies, thus decreasing dramatically transplant tourism from Israel. We evaluated the law's impact on the number and the socio-demographic features of 575 consecutive living donors, transplanted in the largest Israeli transplantation center, spanning 5 years prior to 5 years after the law's implementation. Living kidney donations increased from 3.5 ± 1.5 donations per month in the pre-law period to 6.1 ± 2.4 per month post-law (p < 0.001). This was mainly due to a rise in intra-familial donations from 2.1 ± 1.1 per month to 4.6 ± 2.1 per month (p < 0.001). In unrelated donors we found a significant change in their socio-demographic characteristics: mean age increased from 35.4 ± 7.4 to 39.9 ± 10.2 (p = 0.001), an increase in the proportion of donors with college level or higher education (31.0% to 63.1%; p < 0.001) and donors with white collar occupations (33.3% to 48.3%, p = 0.023). In conclusion, the Israeli legislation that prohibited transplant tourism and organ trading in accordance with Istanbul Declaration, was associated with an increase in local transplantation activity, mainly from related living kidney donors, and a change in the profile of unrelated donors into an older, higher educated, white collar population.


Asunto(s)
Trasplante de Riñón , Donadores Vivos , Obtención de Tejidos y Órganos/legislación & jurisprudencia , Adulto , Femenino , Humanos , Israel , Masculino
5.
Eur J Clin Microbiol Infect Dis ; 32(1): 127-31, 2013 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-22918514

RESUMEN

Asymptomatic bacteriuria (AB) is frequent among kidney transplant patients during the first year post transplantation. Currently, there are no clear guidelines for the antibiotic treatment of AB among these patients. We examined the outcomes of treatment versus no treatment of AB in kidney transplant patients during the first year post transplantation. A retrospective cohort study including adults >16 years of age transplanted in one center between 1/2004 and 12/2010 was undertaken. The primary outcome was a composite of hospitalization for symptomatic urinary tract infection (UTI) or more than 25 % reduction in the estimated glomerular filtration rate (eGFR) 30 days after the documentation of AB. Secondary outcomes included symptomatic UTIs following the episode of AB, persistent recurrent AB, total days in hospital, mortality, adverse events, and resistance development. A total of 112 patients with AB fulfilled the inclusion criteria. Twenty-two patients received antibiotic treatment (19.6 %), while 90 patients did not. The primary outcome occurred in 4/22 (18.2 %) of the treated patients versus 5/90 (5.6 %) of the untreated patients [odds ratio (OR) = 3.78, 95 % confidence interval (CI) 0.9-15]. The risk of developing symptomatic UTI after AB was almost three times higher (p < 0.05) and the total number of hospitalization days at 6 months post AB was also significantly higher (p < 0.026) in the treated group. No patient died during the study period. UTI caused by bacteria resistant to the antibiotic used for the treatment of AB occurred in 36 % of the treated patients. We observed no benefit for the antibiotic treatment of AB in the short- and long-term follow-up. A prospective observational study is needed.


Asunto(s)
Antibacterianos/uso terapéutico , Enfermedades Asintomáticas , Bacteriuria/tratamiento farmacológico , Trasplante de Riñón , Trasplante , Adulto , Anciano , Estudios de Cohortes , Femenino , Tasa de Filtración Glomerular , Hospitalización/estadística & datos numéricos , Humanos , Riñón/fisiopatología , Tiempo de Internación , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Análisis de Supervivencia , Resultado del Tratamiento , Infecciones Urinarias/epidemiología
6.
Transpl Infect Dis ; 14(5): E97-101, 2012 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-22897560

RESUMEN

Zygomycetes infection is associated with a high mortality in transplant populations. We describe a child with liver allograft Rhizopus oryzae infection who was salvaged by liver re-transplantation. A 10-year-old child presented with anastomotic bile leak that was repaired. A combined antibiotics and voriconazole regimen was introduced for Escherichia coli and Candida krusei growth in the peritoneal fluid. Despite broad antibiotic and antifungal coverage, the patient continued to have an ongoing infection. A follow-up computed tomography scan 8 weeks later showed 2 liver abscesses infiltrating the stomach and the diaphragm, with splenic infarcts and pericardial effusion. Aspirated samples from the liver abscess and the pericardial fluid revealed R. oryzae. Immunosuppression was discontinued and an antifungal regimen combining amphotericin B, posaconazole, and caspofungin was introduced. After 3 weeks of treatment with control of the systemic signs of infection, a positron emission tomography showed the fluorescence stain limited to the liver. With infection confined to the liver, the child underwent liver re-transplantation, splenectomy, and partial gastrectomy. Immunosuppression was reintroduced with recovery of the immune response observed by the CD4 cells adenosine triphophate release (Cylex(™) ImmuKnow(®) assay) and posaconazole was continued for another year. At 3-year follow-up, the child maintained normal graft function. We conclude that discontinuation of immunosuppression combined with a modern antifungal regimen may allow salvage re-transplantation in patients with liver mucormycosis.


Asunto(s)
Trasplante de Hígado/efectos adversos , Mucormicosis/diagnóstico , Rhizopus/aislamiento & purificación , Antifúngicos/uso terapéutico , Niño , Humanos , Terapia de Inmunosupresión , Inmunosupresores/administración & dosificación , Hígado/microbiología , Hepatopatías/tratamiento farmacológico , Hepatopatías/inmunología , Hepatopatías/microbiología , Mucormicosis/inmunología , Mucormicosis/microbiología , Rhizopus/clasificación , Rhizopus/efectos de los fármacos , Trasplante Homólogo/efectos adversos
7.
Eur J Surg Oncol ; 47(11): 2933-2938, 2021 11.
Artículo en Inglés | MEDLINE | ID: mdl-34088586

RESUMEN

BACKGROUND: Peritoneal Cancer Index (PCI) and complete cytoreduction are the best outcome predictors following cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC). Lesions in critical areas, regardless of PCI, complicate surgery and impact oncological outcomes. We prospectively defined "Critical lesions" (CL) as penetrating the hepatic hilum, diaphragm at hepatic outflow, major blood vessels, pancreas, or urinary tract. METHODS: Retrospective analysis of a prospective database of 352 CRS + HIPEC patients from 2015 to 2019. Excluded patients with aborted/redo operation (n = 112), or incomplete data (n = 19). Patients categorized by CL status and compared: operative time, estimated blood loss (EBL), PCI, transfusions, hospital stay, post-operative complications and mortality, overall survival (OS) and disease-free survival (DFS). RESULTS: Included 221 patients (78 CL; 143 no-CL). No difference in patients' characteristics: age, BMI, gender or co-morbidities noted. Operative time longer (5.3 h vs 4.3 h, p < 0.01), EBL higher (769 ml vs 405 ml, p < 0.01), transfusions higher (1.9 vs 0.7 Units, p < 0.001) and PCI higher (15.5 vs 9.5, p < 0.01) in CL. No difference in major complications. Postoperative complications, CL, OR-time and transfusions were predictive of OS in univariate analysis, while only complications remained on multivariate analysis. Median follow up of 21.4 months, 3-year DFS/OS was 22% vs 30% (p < 0.037) and 73% vs 87% (p < 0.014) in CL and non-CL, respectively. Despite CL complete resection, 17/38 patients (44.7%) that recurred had recurrence at previous CL site. CONCLUSIONS: Critical lesions complicate surgery and may be associated with poor oncological outcomes with high local recurrence rate, despite no significant difference in complications. Utilizing adjuvant or intra-operative radiation may be beneficial.


Asunto(s)
Procedimientos Quirúrgicos de Citorreducción , Quimioterapia Intraperitoneal Hipertérmica , Invasividad Neoplásica/patología , Neoplasias Peritoneales/patología , Neoplasias Peritoneales/terapia , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Pérdida de Sangre Quirúrgica , Transfusión Sanguínea/estadística & datos numéricos , Terapia Combinada , Femenino , Humanos , Masculino , Persona de Mediana Edad , Tempo Operativo , Complicaciones Posoperatorias , Estudios Retrospectivos
8.
Am J Transplant ; 10(4): 828-836, 2010 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-20420639

RESUMEN

Minimizing steroid exposure in pediatric renal transplant recipients can improve linear growth and reduce metabolic disorders. This randomized multicenter study investigated the impact of early steroid withdrawal on mean change in height standard deviation score (SDS) and the safety and efficacy of two immunosuppressive regimens during the first 6 months after transplantation. Children received tacrolimus, MMF, two doses of daclizumab and steroids until day 4 (TAC/MMF/DAC, n=98) or tacrolimus, MMF and standard-dose steroids (TAC/MMF/STR, n=98). Mean change in height SDS was 0.16 +/- 0.32 with TAC/MMF/DAC and 0.03 +/- 0.32 with TAC/MMF/STR. The mean treatment group difference was 0.13 (p < 0.005 [95% CI 0.04-0.22]), 0.21 in prepubertal (p = 0.009 [95% CI 0.05-0.36]) and 0.05 in pubertal children (p = ns). Frequency of biopsy-proven acute rejection was 10.2%, TAC/MMF/DAC, and 7.1%, TAC/MMF/STR. Patient and graft survival and renal function were similar. Significantly greater reductions in total cholesterol and triglycerides but significantly higher incidences of infection and anemia were found with TAC/MMF/DAC (p < 0.05 all comparisons). Early steroid withdrawal significantly aided growth at 6 months more so in prepubertal than pubertal children. This was accompanied by significantly better lipid and glucose metabolism profiles without increases in graft rejection or loss.


Asunto(s)
Anticuerpos Monoclonales/administración & dosificación , Crecimiento , Inmunoglobulina G/administración & dosificación , Inmunosupresores/administración & dosificación , Fallo Renal Crónico/cirugía , Trasplante de Riñón , Esteroides/administración & dosificación , Tacrolimus/administración & dosificación , Adolescente , Anticuerpos Monoclonales Humanizados , Niño , Preescolar , Daclizumab , Humanos
9.
Clin Transplant ; 24(5): E163-9, 2010.
Artículo en Inglés | MEDLINE | ID: mdl-21039885

RESUMEN

Biliary complications after liver transplantation remain a serious cause of morbidity and mortality. Direct invasive cholangiographic techniques, endoscopic retrograde cholangiography (ERCP) or percutaneous transhepatic cholangiography (PTC), have procedure-related complications. Magnetic resonance cholangiopancreatography (MRCP) is non-invasive, safe, and accurate. The aim of this study was to evaluate MRCP in detecting biliary complications following liver transplantation and comparing findings with ERCP and PTC. Twenty-seven consecutive liver transplant recipients who presented with clinical and biochemical, ultrasonographic, or histological evidence of biliary complications were evaluated with MRCP. Patients were followed up for a median period of 36 months. The presence of a biliary complication was confirmed in 18 patients (66.6%): anastomotic biliary stricture in 12 (66.6%); diffuse intrahepatic biliary stricture in 5 (27.7%): ischemic (n = 3), recurrence of primary sclerosing cholangitis (n = 2), and choledocholithiasis in one. In nine patients (33.3%), MRCP was normal. Six patients underwent ERCP, and eight PTC. There was a statistically significant correlation between the MRCP and both ERCP and PTC (p = 0.01) findings. The sensitivity and specificity of the MRCP were 94.4% and 88.9%, respectively, and the positive and negative predictive values, 94.4% and 89.9%, respectively. MRCP is an accurate imaging tool for the assessment of biliary complications after liver transplantation. We recommend that MRCP be the diagnostic imaging modality of choice in this setting, reserving direct cholangiography for therapeutic procedures.


Asunto(s)
Enfermedades de las Vías Biliares/diagnóstico , Colangiopancreatografia Retrógrada Endoscópica , Pancreatocolangiografía por Resonancia Magnética , Trasplante de Hígado/efectos adversos , Complicaciones Posoperatorias , Enfermedades de las Vías Biliares/etiología , Procedimientos Quirúrgicos del Sistema Biliar , Femenino , Estudios de Seguimiento , Humanos , Donadores Vivos , Masculino , Persona de Mediana Edad , Factores de Riesgo , Tasa de Supervivencia
10.
Pediatr Transplant ; 14(6): 753-60, 2010 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-20477976

RESUMEN

Routine prophylaxis for CMV with valganciclovir is common in adult recipients but data to support its use in children are scarce. The aim of this study was to compare the efficacy and safety of valganciclovir vs. ganciclovir in a pediatric cohort. We performed a retrospective analysis of 92 children after KTx and/or LTx. All children have received IV ganciclovir for two wk, and then oral ganciclovir (TID; n = 41) before 2004, or valganciclovir (OD; n = 51) thereafter. Treatment was given for three months in R+/D+ or R+/D- recipients and for six months in R-/D+. Patients were followed for one yr post transplant. Both groups were comparable in their demographic and transplant-related history. Symptomatic CMV infection/disease developed in 13.7% vs. 19.5% of valganciclovir and ganciclovir groups, respectively (P-NS). Time-to-onset of CMV infection was comparable in both groups (P-NS); rates of acute allograft rejection were similar in both groups (3.9% vs. 9.8%). Risk factors for CMV infection included young age, serostatus of R-/D+, and allograft from cadaver donor. No significant side effects were noted in both groups. As in adults, valganciclovir appears to be as efficacious and safe as oral ganciclovir. Valganciclovir should be considered as a possible prophylactic treatment for CMV in pediatric recipients of KTx or LTx.


Asunto(s)
Antivirales/administración & dosificación , Infecciones por Citomegalovirus/prevención & control , Ganciclovir/análogos & derivados , Ganciclovir/administración & dosificación , Trasplante de Riñón , Trasplante de Hígado , Complicaciones Posoperatorias/prevención & control , Administración Oral , Adolescente , Niño , Preescolar , Infecciones por Citomegalovirus/epidemiología , Supervivencia sin Enfermedad , Quimioterapia Combinada , Femenino , Humanos , Inmunosupresores/administración & dosificación , Lactante , Modelos Logísticos , Masculino , Estudios Retrospectivos , Factores de Riesgo , Tacrolimus/administración & dosificación , Resultado del Tratamiento , Valganciclovir
11.
J Clin Invest ; 91(2): 388-90, 1993 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-8432846

RESUMEN

Administration of attenuated, activated autoimmune T lymphocytes to syngeneic mice and rats has been shown to prevent or induce remission of experimental autoimmune diseases specific for the autoimmune T cells. The process has been termed "T cell vaccination." In a recent study, T cell vaccination was done using T cells sensitized to rat alloantigens. The procedure produced a significant reduction of the mixed lymphocyte reaction (MLR) against allogeneic cells. The reduction in MLR was not specific: Vaccination with T cells specific for stimulator cells of one allotype led to a reduced MLR stimulated by cells of another allotype. The present study was undertaken to examine whether T cell vaccination can induce tolerance to transplantation antigens in vivo. We used the model of heterotopic cardiac transplantation in rats. We now report that vaccinating rats with syngeneic, activated, alloantigen-primed T lymphocytes significantly prolonged survival of rat cardiac allografts. The effect of T cell vaccination was most evident when the T cells had been obtained from rats specifically sensitized against the donor rats: Brown-Norway (BN) allografts in control Wistar rats survived 8.5 +/- 0.4 d while BN allografts survived 29.2 +/- 7.1 d in Wistar rats that had been vaccinated with Wistar anti-BN cells. Vaccination of Wistar rats with Wistar anti-hooded T cells prolonged survival of BN heart allografts to a lesser but significant degree (13.0 +/- 1.1 d). Thus, T cell vaccination of recipients can prolong survival of allografts.


Asunto(s)
Supervivencia de Injerto/inmunología , Trasplante de Corazón/inmunología , Linfocitos T/inmunología , Animales , Rechazo de Injerto , Antígenos de Histocompatibilidad/inmunología , Activación de Linfocitos , Prueba de Cultivo Mixto de Linfocitos , Masculino , Ratas , Ratas Endogámicas BN , Ratas Wistar , Trasplante de Piel , Trasplante Homólogo , Vacunación
12.
Minerva Ginecol ; 59(6): 571-8, 2007 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-18043569

RESUMEN

AIM: Twin pregnancies are at greater risk of obstetrical and perinatal adverse outcome compared to singletons. In addition, expecting twins can have particular psychological consequences on both parents. The aim of our study was to interview women with a twin pregnancy and their partners in order to assess their feelings and emotions related to the twins and to evaluate the opportunity to activate an information group about the theme of twin pregnancy, and a development of twins and family management. METHODS: Twenty patients with an uncomplicated twin pregnancy and their partners answered 9 questions in a semistructured interview, set on the basis of the psychological and social issues reported in the literature on couples expecting twins. Emerging themes and key words were extracted from the interviews and analysed. RESULTS: Quantitative analysis showed that women were, in most cases, shocked at the time of the diagnosis of twinning, while men tried to minimize the worries of their partners. Women reported some fears related to the practical management of the future life, but they declared to feel not different from women expecting singleton, confirming the data reported in the literature. Seventy percent of the women were interested in meeting other parents with twins. Qualitative analysis frequently indicated the defence mechanism of rationalisation and negation of the worries concerning the pregnancy risks and the future care of their babies. Their answers seem to hide fears and doubts that are confessed with difficulty. CONCLUSION: Our study suggests the importance for hospital staff to create an atmosphere of calm and to demonstrate empathy and understanding, with the aim to help and allow the mothers to express their fears.


Asunto(s)
Negación en Psicología , Miedo , Racionalización , Gemelos , Adulto , Emociones , Femenino , Humanos , Masculino , Embarazo , Resultado del Embarazo , Historia Reproductiva , Encuestas y Cuestionarios
13.
Transplantation ; 54(5): 821-4, 1992 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-1279849

RESUMEN

A retrospective review of 375 consecutive orthotopic liver transplants was performed to determine the incidence and outcome of late rejection episodes ([LR] rejection occurring more than 6 months following transplant). A total of 31 episodes in 26 patients were identified. Eighteen of these episodes were associated with subtherapeutic levels of cyclosporine. Of these, 7 were due to noncompliance, 2 were due to biliary strictures, and 1 was due to malabsorption in a cystic fibrosis patient. All 31 episodes were treated initially with steroids, and 22 had a complete response, although one progressed to chronic rejection over a year later. Of the remaining 9, 1 received FK506 with a complete response, and 8 received OKT3. Of the 8 patients who received OKT3, 5 had a complete response, 1 received RS61443 following OKT3 and progressed to chronic rejection, and the remaining 2 received further steroids. Of these 2, 1 had a complete response following the steroids while the second was converted to FK506 with a complete response. Compared with 315 acute rejection episodes ([AR] occurring less than 6 months posttransplant), patients with late rejection episodes had an equivalent response to steroids (63.2% AR reversed vs. 71% LR reversed) but a lower response rate to OKT3 (91.5% AR reversed vs. 62.5% LR reversed). There was, therefore, a higher rate of persistent rejection (61% AR episodes vs. 15.4% LR episodes) but no increase in the incidence of chronic rejection (7% AR episodes vs. 7.7% LR episodes). We conclude that LR is a relatively common occurrence following liver transplant, which is most often associated with low cyclosporine levels. Many of these episodes are due to noncompliance, but biliary problems must also be investigated. The incidence of resistant rejection is higher in this group of patients but is not associated with a concurrent increase in chronic rejection.


Asunto(s)
Trasplante de Hígado/inmunología , Adolescente , Adulto , Anticuerpos Monoclonales/uso terapéutico , Ciclosporina/uso terapéutico , Femenino , Rechazo de Injerto/tratamiento farmacológico , Rechazo de Injerto/epidemiología , Humanos , Hidrocortisona/uso terapéutico , Masculino , Metilprednisolona/uso terapéutico , Persona de Mediana Edad , Cooperación del Paciente , Estudios Retrospectivos , Factores de Riesgo , Tacrolimus/uso terapéutico , Factores de Tiempo
14.
Transplantation ; 63(3): 393-6, 1997 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-9039929

RESUMEN

Orthotopic liver transplantation (OLT) in patients infected with hepatitis B virus (HBV) is known to be associated with a high recurrence rate and poor prognosis. Interferon treatment in these patients offers little benefit and may lead to further complications. Lamivudine, the (-)enantiomer of 3'-thiacytidine, a 2'3'-dideoxynucleoside, is known to be a potent inhibitor of HBV replication in patients with chronic HBV infection. Three HBV-positive OLT patients were administrated lamivudine, 100 mg x 1 orally, for a period of at least 20 weeks, in an open, compassionate-use basis. All three patients were HBV DNA-negative before OLT. HBV reinfection occurred at a median time of 7 months (range, 6-9 months) after OLT, in spite of adequate immunoprophylaxis. All three patients had high serum transaminase levels (alanine aminotransferase [ALT], 103-324 U/L) and histologic evidence of recurrent HBV infection of the grafted liver, and HBV DNA was evident in the sera of all of them. Six weeks after lamivudine treatment, HBV DNA disappeared from the serum of all patients (detected by hybridization); by the 10th week, HBV DNA was also negative by polymerase chain reaction in two out of three patients. Interestingly, the one patient who was HBV DNA positive by polymerase chain reaction still has mildly elevated ALT levels, whereas the other two patients have normal ALT levels. We also noted that on the 5th week there was a transient elevation of serum ALT levels in two patients. No adverse effects or rejection episodes were noted. In conclusion, lamivudine is a beneficial and well-tolerated therapy in OLT patients with recurrent HBV infection. We are studying the effect of lamivudine in other patients and for a longer period of time.


Asunto(s)
Hepatitis B/tratamiento farmacológico , Lamivudine/uso terapéutico , Trasplante de Hígado , Adulto , Enfermedad Crónica , Femenino , Hepatitis B/cirugía , Humanos , Lamivudine/efectos adversos , Cirrosis Hepática/cirugía , Cirrosis Hepática/virología , Trasplante de Hígado/efectos adversos , Masculino , Persona de Mediana Edad , Recurrencia
15.
Transplantation ; 68(2): 232-6, 1999 Jul 27.
Artículo en Inglés | MEDLINE | ID: mdl-10440393

RESUMEN

BACKGROUND: Orthotopic liver transplantation (OLT) in patients with hepatitis B virus (HBV) infection is known to be associated with a high recurrence rate and poor prognosis. Lamivudine, a nucleoside analogue, is a potent inhibitor of HBV replication, but it is associated with a 14-39% rate of resistance. METHODS: We report on four patients who underwent OLT for HBV infection. In all cases, the HBV infection recurred in the grafted liver and was treated with lamivudine (100 mg daily) on a compassionate-use basis. The patients were monitored closely for serum liver enzymes, hepatitis B surface antigen and HBV DNA (by hybridization). Liver biopsy was performed before and after lamivudine therapy. HBV DNA was amplified from serum for each patient and sequenced through a conserved polymerase domain, the tyrosine-methionine-aspartate-aspartate (YMDD) locus. RESULTS: All four patients exhibited lamivudine resistance 9-20 months after initiation of the drug. In all patients with a clinically mild disease, liver histology findings (12-24 months after lamivudine therapy) showed progressive fibrosis as compared to biopsies performed before lamivudine therapy, with a significant increase (> or =2 points) in the Knodell score in three patients. Moreover, two patients exhibited worsening of the necroinflammatory process. A mutation at the YMDD motif of the HBV polymerase gene was detected in all cases. CONCLUSIONS: Lamivudine resistance frequently occurs in patients with recurrent HBV infection after OLT and is associated with advanced hepatic fibrosis and necroinflammatory process. A combination of antiviral therapies may be necessary.


Asunto(s)
Fármacos Anti-VIH/farmacología , Hepatitis B/prevención & control , Lamivudine/farmacología , Cirrosis Hepática/complicaciones , Trasplante de Hígado , Adulto , ADN Viral/sangre , Farmacorresistencia Microbiana , Femenino , Virus de la Hepatitis B/genética , Humanos , Masculino , Persona de Mediana Edad , Recurrencia , Resultado del Tratamiento
16.
Transplantation ; 55(1): 87-91, 1993 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-8420070

RESUMEN

The results of OKT3 use for steroid-resistant rejection rescue in adult liver transplantation were analyzed retrospectively from a single transplant center. Comparison was made with concurrent patients who had no rejection (NR) or steroid-responsive rejections (SR). The records of 290 patients who underwent 323 liver transplants from April 1985 to December 1989 were examined. The first technically successful grafts were used for this analysis (265 grafts). Follow-up was a minimum of 1 year, or until death or loss of graft. All patients received triple-drug induction immunosuppression (CsA, Aza, steroids). Initial rejection was treated with 1 g methylprednisolone bolus i.v., followed by a 5-day taper of steroids from 200 mg to 20 mg. No rejection occurred in 108 (40.8%) and SR in 86 (32.4%), and OKT3 was given for persistent rejection in 71 (26.8%). The age, sex distribution, mean follow-up, and preoperative status were similar in all three groups. The preoperative diagnoses were similar, except for fulminant liver failure, in which 19 of 20 patients experienced rejection (P < 0.0001). The median hospitalization stay was 37 days for OKT3, 27 days for SR, and 21 days for NR (P < 0.0001). The median ICU stay was similar in the three groups (OKT3, 4; SR, 4; NR, 3). Infections in the first 6 weeks, and in the period of 6 weeks to 1 year posttransplant, were of similar frequency for all three groups. By the Kaplan-Meier estimation, the graft and patient actuarial survival rates were comparable. At 1 year, the graft survival rate was 79.6% for NR, 79.8% for SR, and 67.6% for OKT3. The 1-year patient survival rate was 85.2% for NR, 83.7% for SR, and 84.5% for OKT3. Following treatment by OKT3, rejection was permanently reversed in 42 patients. A temporary response occurred in 12 patients, 16 patients failed to respond to OKT3, 2 patients died during therapy, and 6 of the nonresponders died within 12 months. Additional OKT3 treatment was attempted in 6 patients for persistent rejection within a 1-month interval from the previous OKT3 course. Of these 6, 4 developed lymphoproliferative disorder, and only 1 survived in response to drastic reduction of immunosuppression. In conclusion, OKT3 was effective as rescue therapy for adult liver transplant steroid-resistant rejection. Because of the associated morbidity and expense, OKT3 should be used in a selective fashion. Failure to respond to OKT3 is a serious complication, and should not be managed by prolonged or repeated courses, but rather by alternative means.


Asunto(s)
Rechazo de Injerto/tratamiento farmacológico , Trasplante de Hígado , Hígado , Muromonab-CD3/uso terapéutico , Adulto , Esquema de Medicación , Resistencia a Medicamentos , Femenino , Estudios de Seguimiento , Rechazo de Injerto/mortalidad , Supervivencia de Injerto , Humanos , Masculino , Metilprednisolona/uso terapéutico , Persona de Mediana Edad , Reoperación , Estudios Retrospectivos
17.
Transplantation ; 59(7): 986-90, 1995 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-7709460

RESUMEN

Graft and patient survival rates after transplantation of ABO-incompatible liver allografts have been poor. We used plasmapheresis and a potent immunosuppressive regimen to control hemagglutinin levels and prevent early rejection. Ten patients who had a United Network for Organ Sharing status of 4 received ABO-incompatible allografts. Quadruple immunosuppression consisted of OKT3, Cytoxan, cyclosporine, and steroid taper; prostaglandin E-1 was administrated intravenously the first week. All patients underwent perioperative plasmapheresis to maintain hemagglutinin levels < 1:16. Patient survival was 80%; graft survival was 60% at 140-505 days. The rejection rate was 90%. Three recipients (A1-->O) lost their grafts to severe rejection at 5, 12, and 30 days after transplantation. All 3 had pretransplantation hemagglutinin levels > or = 1:100. Elevated hemagglutinin levels preceded the diagnosis of severe acute cellular rejection; plasmapheresis failed to lower anti-A titers in these 3 patients. We conclude that in an urgent setting, lowering of preformed hemagglutinins via plasmapheresis in combination with quadruple induction immunosuppression allows liver transplantation across ABO barriers. In patients with high baseline levels of preformed hemagglutinins, the risk of subsequent graft loss may be increased and transplantation with an ABO-incompatible graft may serve as a lifesaving intermediate step.


Asunto(s)
Sistema del Grupo Sanguíneo ABO , Incompatibilidad de Grupos Sanguíneos , Inmunosupresores/uso terapéutico , Trasplante de Hígado/inmunología , Plasmaféresis , Adolescente , Adulto , Formación de Anticuerpos , Preescolar , Ciclofosfamida/uso terapéutico , Ciclosporina/uso terapéutico , Rechazo de Injerto/prevención & control , Supervivencia de Injerto/fisiología , Hemaglutininas/análisis , Humanos , Metilprednisolona/uso terapéutico , Persona de Mediana Edad , Muromonab-CD3/uso terapéutico
18.
Transplantation ; 56(6): 1399-402, 1993 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-8279010

RESUMEN

Hepatic artery thrombosis (HAT) after liver transplantation (LTx) usually mandates retransplantation. Prolonged preservation with Eurocollins solution has been associated with HAT. We reviewed our experience with 359 LTx patients to identify risk factors for HAT. All grafts were preserved in University of Wisconsin solution. HAT developed in 12 patients (3%) within 50 days. Seven patients were asymptomatic; four presented with biliary sepsis and 1 with poor graft function. Two patients had suffered acute rejection; another 2 had severe preservation injury. Technical problems accounted for 4 cases; in the remaining 8, no etiology was found. Diagnosis was at a mean 14.7 days after LTx. One patient maintains normal graft function 3 years after LTx without intervention. Eight underwent re-LTx, 3 of whom died. Routine surveillance via duplex enabled early diagnosis and revascularization in 3 patients; in all 3, no biliary complications occurred between 6 and 20 months. Overall graft and patient survival after HAT were 33.3% and 75%, respectively. Cold ischemic time (CIT) averaged 813 min in patients with HAT and 669 min in those without HAT (P < .05). HAT occurred in 7/165 patients with CIT > 12 hr, and in 3/234 patients with CIT < 12 hr (P = 0.0699). By avoiding CIT > 12 hr, we have recently avoided HAT in 78 consecutive patients. We conclude that CIT > 12 hr may increase the risk of HAT. When HAT is diagnosed before biliary sepsis develops, flow can often be restored and retransplantation averted.


Asunto(s)
Arteria Hepática , Trasplante de Hígado/efectos adversos , Soluciones Preservantes de Órganos , Preservación de Órganos/efectos adversos , Trombosis/etiología , Adenosina/efectos adversos , Adulto , Anciano , Alopurinol/efectos adversos , Preescolar , Frío , Glutatión/efectos adversos , Humanos , Insulina/efectos adversos , Isquemia/complicaciones , Hígado/irrigación sanguínea , Persona de Mediana Edad , Rafinosa/efectos adversos , Trombosis/diagnóstico por imagen , Trombosis/cirugía , Factores de Tiempo , Ultrasonografía
19.
Transplantation ; 53(2): 383-6, 1992 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-1738933

RESUMEN

A total of 365 donor hepatectomies performed between May 1985 and March 1990 were reviewed and analyzed retrospectively to identify risk factors associated with poor graft function and to study the outcome of grafts retrieved from "marginal" donors. The donor mean age was 27.1 years (8-69 years). Mean ICU donor stay was 2.7 days (range 0 to 18 days), and the mean ischemic time was 8.6 hr (range 3 to 22 hr). The pancreas was retrieved in 39 donors. Donor's weight above 100 kg was the only variable found to be associated with both significantly increased 3-month graft loss (P less than 0.01) and early hepatocellular damage--AST or ALT greater than 2000 U/ml, 1st day posttransplant (P less than 0.02). Prolonged stay in the ICU (greater than 3 days), although associated with a significantly increased rate of hepatocellular damage (P less than 0.05), did not affect early graft survival. A systolic blood pressure less than 90 mmHg despite the use of high-dose dopamine (greater than 15 micrograms/mg/min), but not each of these variables itself, was also associated with a significantly increase rate of hepatocellular damage (P less than 0.001). All other variables, including age greater than 50, ischemic time greater than 12 hr, combined liver-pancreas procurement, and liver function test abnormalities, did not affect the outcome. We conclude that extending our limits to accept donors of the higher age group and those who have moderately abnormal liver function tests or a prolonged ischemic time will not jeopardize our results. It is suggested to perform liver biopsy in overweight donors during the retrieval to prevent using grafts with severe fatty infiltration. It is hypothesized that hormonal changes, starvation, and increased risk to develop infection might jeopardize the outcome of grafts from donors with a prolonged ICU stay. Although 70% of the early hepatocellular injuries are reversible, the remaining 30% result in graft failure.


Asunto(s)
Trasplante de Hígado , Hígado , Donantes de Tejidos/provisión & distribución , Adolescente , Adulto , Anciano , Presión Sanguínea , Niño , Femenino , Supervivencia de Injerto , Humanos , Hígado/enzimología , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Factores de Tiempo , Trasplante Homólogo/fisiología
20.
Transplantation ; 72(3): 428-32, 2001 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-11502971

RESUMEN

BACKGROUND: The appropriate use of liver transplantation in children with type-1 primary hyperoxaluria (PH-1) is not well established. We reviewed our experience with 36 children with PH-1, including 12 who underwent liver transplantation. PATIENTS AND METHODS: From 1989-1998, 36 children from 10 families in northern Israel were diagnosed with PH-1. Eight children presented with renal failure; seven of these eight had the severe infantile form of the disease. One child was treated with kidney transplantation alone. Combined liver-kidney transplantation has been performed in nine children and preemptive liver transplantation in three children. A review of the patients' charts for the following parameters was performed: age, clinical signs, and renal sonographic findings at diagnosis, age at onset of dialysis, and current status. Type of transplant, pre- and posttransplant urine oxalate excretion, current renal function, survival, and complications were recorded in liver recipients. RESULTS: Of the 23 nontransplanted children, 9 died of complications related to severe systemic oxalosis and 14 are alive (mean follow-up, 7.4 years), including 2 who are candidates for transplantation. The child who underwent only kidney transplantation died of unrelated causes. Of the 12 liver recipients, 2 died within the first 3 months posttransplant and another child underwent retransplantation due to hepatic arterial thrombosis. At intervals after transplant ranging from 6-54 months, 10 recipients are alive (7 of the 9 recipients of combined liver-kidney transplants and all 3 recipients of preemptive liver transplants). Mean GFR in the 10 survivors is 77 ml/min/m2. In 9 of these 10, daily urinary oxalate excretion normalized. Renal function has improved (mean GFR 86 vs. 58 ml/min/m2) but renal oxalate deposits remain in the three recipients of isolated liver grafts. CONCLUSIONS: Our decade-long experience with children with PH-1 supports strategies for early diagnosis and timely liver transplantation. Preemptive isolated liver transplantation should be considered in children who develop the disease during infancy or in those with slowly progressive disease when significant symptoms develop. Combined liver-kidney transplantation is suggested for children with end-stage renal disease.


Asunto(s)
Hiperoxaluria Primaria/cirugía , Trasplante de Hígado , Adolescente , Adulto , Niño , Preescolar , Estudios de Cohortes , Femenino , Tasa de Filtración Glomerular , Supervivencia de Injerto , Humanos , Hiperoxaluria Primaria/complicaciones , Hiperoxaluria Primaria/mortalidad , Lactante , Recién Nacido , Fallo Renal Crónico/complicaciones , Fallo Renal Crónico/mortalidad , Fallo Renal Crónico/fisiopatología , Fallo Renal Crónico/cirugía , Trasplante de Riñón , Masculino , Análisis de Supervivencia
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