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1.
Langenbecks Arch Surg ; 407(8): 3833-3841, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35857097

RESUMO

PURPOSE: Atypical variants of the hepatic artery are common and pose a technical challenge for normothermic machine perfusion (NMP). The transplant surgeon has three options when confronted with hepatic arterial variation in a liver graft to be subjected to NMP: to perform arterial reconstruction (i) prior, (ii) during, or (iii) following NMP. METHODS: Herein, we report our experience and technical considerations with pre-NMP reconstruction. Out of 52 livers, 9 had an atypical hepatic artery (HA): 3 replaced right HA, 3 replaced left HA, 1 accessory left HA, 1 accessory left and right HA, and 1 replaced left and right HA. RESULTS: Reconstruction was conducted during back-table preparation. A single vascular conduit was created in all grafts to allow single arterial cannulation for NMP, necessitating only one arterial anastomosis within the recipient. All grafts were subjected to NMP and subsequently successfully transplanted. CONCLUSION: Our approach is being advocated for as it preserves the ability to alter the reconstruction in case of problems resulting from the reconstruction itself, thereby allowing functional evaluation of the reconstruction prior transplantation, permitting simultaneous reperfusion in the recipient, and providing the shortest possible duration for vascular reconstruction once the graft is rewarming non-perfused within the recipient. In addition, in light of the frequency of technically demanding reconstructions with very small vessels, we consider our technique beneficial as the procedure can be performed under ideal conditions at the back-table.


Assuntos
Transplante de Fígado , Preservação de Órgãos , Humanos , Preservação de Órgãos/métodos , Perfusão/métodos , Transplante de Fígado/métodos , Artéria Hepática/cirurgia , Fígado
2.
Ann Surg ; 272(5): 855-862, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32889867

RESUMO

OBJECTIVE: The aim of this study was to evaluate the survival benefit of sirolimus in patients undergoing liver transplantation (LT) for hepatocellular carcinoma (HCC) (exploratory analysis of the SiLVER-trial). SUMMARY AND BACKGROUND DATA: Patients receiving LT) for HCC are at a high risk for tumor recurrence. Calcineurin inhibitors have shown evidence to promote cancer growth, whereas mammalian target of rapamycin (mTOR) inhibitors like sirolimus have anticancer effects. In the SiLVER-trial (Clinicaltrials.gov: NCT00355862), the effect of sirolimus on the recurrence of HCC after LT was investigated in a prospective randomized trial. Although the primary endpoint of improved disease-free survival (DFS) with sirolimus was not met, outcomes were improved for patients in the sirolimus-treatment arm in the first 3 to 5 years. To learn more about the key variables, a multivariate analysis was performed on the SiLVER-trial data. PATIENTS AND METHODS: Data from 508 patients of the intention-to-treat analysis were included in exploratory univariate and multivariate models for overall survival (OS), DFS and a competing risk analysis for HCC recurrence. RESULTS: Sirolimus use for ≥3 months after LT for HCC independently reduced the hazard for death in the multivariate analysis [hazard ratio (HR): 0.7 (95% confidence interval, CI: 0.52-0.96, P = 0.02). Most strikingly, patients with an alpha-fetoprotein (AFP) ≥10 ng/mL and having used sirolimus for ≥3 months, benefited most with regard to OS, DFS, and HCC-recurrence (HR: 0.49-0.59, P = 0.0079-0.0245). CONCLUSIONS: mTOR-inhibitor treatment with sirolimus for ≥3 months improves outcomes in LT for HCC, especially in patients with AFP-evidence of higher tumor activity, advocating particularly for mTOR inhibitor use in this subgroup of patients. CLINICAL TRIAL REGISTRATION: EudraCT: 2005-005362-36 CLINICALTRIALS.GOV:: NCT00355862.


Assuntos
Carcinoma Hepatocelular/cirurgia , Imunossupressores/uso terapêutico , Neoplasias Hepáticas/cirurgia , Transplante de Fígado , Recidiva Local de Neoplasia/prevenção & controle , Sirolimo/uso terapêutico , Idoso , Carcinoma Hepatocelular/mortalidade , Feminino , Humanos , Análise de Intenção de Tratamento , Neoplasias Hepáticas/mortalidade , Transplante de Fígado/mortalidade , Masculino , Pessoa de Meia-Idade , Taxa de Sobrevida
3.
Int J Mol Sci ; 21(18)2020 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-32899772

RESUMO

To ameliorate ischemia-induced graft injury, optimal organ preservation remains a critical hallmark event in solid organ transplantation. Although numerous preservation solutions are in use, they still have functional limitations. Here, we present a concise review of a modified Histidine-Tryptophan-Ketoglutarate (HTK) solution, named HTK-N. Its composition differs from standard HTK solution, carrying larger antioxidative capacity and providing inherent toxicity as well as improved tolerance to cold aiming to attenuate cold storage injury in organ transplantation. The amino acids glycine, alanine and arginine were supplemented, N-acetyl-histidine partially replaced histidine, and aspartate and lactobionate substituted chloride. Several in vitro studies confirmed the superiority of HTK-N in comparison to HTK, being tested in vivo in animal models for liver, kidney, pancreas, small bowel, heart and lung transplantation to adjust ingredients for required conditions, as well as to determine its innocuousness, applicability and potential advantages. HTK-N solution has proven to be advantageous especially in the preservation of liver and heart grafts in vivo and in vitro. Thus, ongoing clinical trials and further studies in large animal models and consequently in humans are inevitable to show its ability minimizing ischemia-induced graft injury in the sequel of organ transplantation.


Assuntos
Soluções para Preservação de Órgãos/química , Preservação de Órgãos/métodos , Alanina , Animais , Arginina , Criopreservação/métodos , Glucose/química , Glucose/metabolismo , Glicina , Humanos , Fígado/efeitos dos fármacos , Manitol/química , Manitol/metabolismo , Transplante de Órgãos , Pâncreas/efeitos dos fármacos , Cloreto de Potássio/química , Cloreto de Potássio/metabolismo , Procaína/química , Procaína/metabolismo , Traumatismo por Reperfusão
4.
Int J Mol Sci ; 21(15)2020 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-32707886

RESUMO

Intestinal ischemia reperfusion injury (IRI) is an inherent, unavoidable event of intestinal transplantation, contributing to allograft failure and rejection. The inflammatory state elicited by intestinal IRI is characterized by heightened leukocyte recruitment to the gut, which is amplified by a cross-talk with platelets at the endothelial border. Sulforaphane (SFN), a naturally occurring isothiocyanate, exhibits anti-inflammatory characteristics and has been shown to reduce platelet activation and block leukocyte adhesion. Thus, the aim of this study was to investigate protective effects and mechanism of action of SFN in a murine model of intestinal IRI. Intestinal IRI was induced by superior mesenteric artery occlusion for 30 min, followed by reperfusion for 2 h, 8 h or 24 h. To investigate cellular interactions, leukocytes were in vivo stained with rhodamine and platelets were harvested from donor animals and ex vivo stained. Mice (C57BL/6J) were divided into three groups: (1) control, (2) SFN treatment 24 h prior to reperfusion and (3) SFN treatment 24 h prior to platelet donation. Leukocyte and platelet recruitment was analyzed via intravital microscopy. Tissue was analyzed for morphological alterations in intestinal mucosa, barrier permeability, and leukocyte infiltration. Leukocyte rolling and adhesion was significantly reduced 2 h and 8 h after reperfusion. Mice receiving SFN treated platelets exhibited significantly decreased leukocyte and platelet recruitment. SFN showed protection for intestinal tissue with less damage observed in histopathological and ultrastructural evaluation. In summary, the data presented provide evidence for SFN as a potential therapeutic strategy against intestinal IRI.


Assuntos
Plaquetas/efeitos dos fármacos , Mucosa Intestinal/efeitos dos fármacos , Isotiocianatos/farmacologia , Leucócitos/efeitos dos fármacos , Traumatismo por Reperfusão/prevenção & controle , Animais , Plaquetas/patologia , Modelos Animais de Doenças , Mucosa Intestinal/patologia , Mucosa Intestinal/ultraestrutura , Isotiocianatos/uso terapêutico , Leucócitos/imunologia , Leucócitos/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Microscopia Eletrônica , Microscopia de Fluorescência , Neutrófilos/efeitos dos fármacos , Neutrófilos/imunologia , Neutrófilos/patologia , Ativação Plaquetária/efeitos dos fármacos , Traumatismo por Reperfusão/imunologia , Traumatismo por Reperfusão/patologia , Sulfóxidos
5.
BMC Urol ; 18(1): 39, 2018 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-29747596

RESUMO

BACKGROUND: Living-donor nephrectomy (LDN) is challenging, as surgery is performed on healthy individuals. Minimally invasive techniques for LDN have become standard in most centers. Nevertheless, numerous techniques have been described with no consensus on which is the superior approach. Both hand-assisted retroperitoneoscopic (HARS) and hand-assisted laparoscopic (HALS) LDNs are performed at Zurich University Hospital. The aim of this study was to compare these two surgical techniques in terms of donor outcome and graft function. METHOD: Retrospective single-center analysis of 60 consecutive LDNs (HARS n = 30; HALS n = 30) from June 2010 to May 2012, including a one-year follow-up of the recipients. RESULTS: There was no mortality in either group and little difference in the overall complication rates. Median warm ischemia time (WIT) was significantly shorter in the HARS group. The use of laxatives and the incidence of postoperative vomiting were significantly greater in the HALS group. There was no difference between right- and left-sided nephrectomies in terms of donor outcome and graft function. CONCLUSIONS: Both techniques appear safe for both donors and donated organs. The HARS technique is associated with a shorter WIT and a reduced incidence of postoperative paralytic ileus. Therefore, we consider HARS LDN a valuable alternative to HALS LDN.


Assuntos
Laparoscopia Assistida com a Mão/métodos , Transplante de Rim/métodos , Doadores Vivos , Nefrectomia/métodos , Espaço Retroperitoneal/cirurgia , Adulto , Idoso , Feminino , Seguimentos , Laparoscopia Assistida com a Mão/normas , Humanos , Transplante de Rim/normas , Masculino , Pessoa de Meia-Idade , Nefrectomia/normas , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/prevenção & controle , Estudos Retrospectivos
6.
Liver Transpl ; 23(2): 207-220, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27809409

RESUMO

Donor organ shortage necessitates use of less than optimal donor allografts for transplantation. The current cold storage preservation technique fails to preserve marginal donor grafts sufficiently. Evidence from large animal experiments suggests superiority of normothermic machine preservation (NMP) of liver allografts. In this study, we analyze discarded human liver grafts that underwent NMP for the extended period of 24 hours. Thirteen human liver grafts which had been discarded for transplantation were entered into this study. Perfusion was performed with an automated device using an oxygenated, sanguineous perfusion solution at normothermia. Automated control was incorporated for temperature-, flow-, and pressure-regulation as well as oxygenation. All livers were perfused for 24 hours; parameters of biochemical and synthetic liver function as well as histological parameters of liver damage were analyzed. Livers were stratified for expected viability according to the donor's medical history, procurement data, and their macroscopic appearance. Normothermic perfusion preservation of human livers for 24 hours was shown to be technically feasible. Human liver grafts, all of which had been discarded for transplantation, showed levels suggesting organ viability with respect to metabolic and synthetic liver function (to varying degrees). There was positive correlation between instantly available perfusion parameters and generally accepted predictors of posttransplant graft survival. In conclusion, NMP is feasible reliably for periods of at least 24 hours, even in highly suboptimal donor organs. Potential benefits include not only viability testing (as suggested in recent clinical implementations), but also removal of the time constraints associated with the utilization of high-risk livers, and recovery of ischemic and other preretrieval injuries (possibly by enabling therapeutic strategies during NMP). Liver Transplantation 23 207-220 2017 AASLD.


Assuntos
Aloenxertos/patologia , Fígado/patologia , Preservação de Órgãos/métodos , Perfusão/métodos , Sobrevivência de Tecidos , Coleta de Tecidos e Órgãos/métodos , Adulto , Idoso , Isquemia Fria/efeitos adversos , Seleção do Doador/métodos , Estudos de Viabilidade , Feminino , Humanos , Transplante de Fígado/efeitos adversos , Masculino , Pessoa de Meia-Idade , Preservação de Órgãos/instrumentação , Perfusão/instrumentação , Traumatismo por Reperfusão/prevenção & controle , Temperatura , Fatores de Tempo , Doadores de Tecidos , Isquemia Quente/efeitos adversos
7.
Kidney Blood Press Res ; 39(4): 230-9, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25118597

RESUMO

BACKGROUND/AIMS: Sclerostin is secreted by osteocytes. As a circulating inhibitor of the Wnt-signaling pathway it inhibits bone formation and contributes to the development of osteoporosis. Sclerostin levels are elevated in patients with chronic kidney disease and end-stage renal disease. Since data for patients after kidney transplantation are scarce, we have prospectively measured sclerostin levels before and during the first year after renal transplantation and have examined the association of sclerostin with parameters of bone mineral metabolism and with bone mineral density. METHODS: Sclerostin levels were measured by ELISA in 42 consecutive renal transplant recipients before and at defined intervals in the first year after transplantation. Bone mineral density was measured by dual energy X-ray absorptiometry. RESULTS: Pre-transplant serum sclerostin levels were elevated in all patients (61.8 ± 32.3 pmol/l, normal range 20-30 pmol/l). Within 15 days after transplantation and correlating with the improvement of renal function, sclerostin levels dropped to 21.0 ± 14.7 pmol/l and subsequently increased to 23.8 ± 14.9 and 28.0 ± 16.8 pmol/l after 6 and 12 months, respectively (P<0.001). A linear mixed model indicated that pre-transplant sclerostin levels (P<0.001) and time after transplantation (P<0.001) were the most important predictors for the rise of post-transplant sclerostin levels. No correlation was found between post-transplant sclerostin levels and bone mineral density. CONCLUSIONS: The rapid reduction of elevated serum sclerostin levels shortly after kidney transplantation parallels the improvement of renal function, but contrasts with the more delayed improvement of hyperparathyroidism. The normalization of both hormones could contribute to improved bone health after renal transplantation.


Assuntos
Proteínas Morfogenéticas Ósseas/sangue , Transplante de Rim , Absorciometria de Fóton , Proteínas Adaptadoras de Transdução de Sinal , Adulto , Idoso , Anticorpos Monoclonais Humanizados/uso terapêutico , Densidade Óssea , Conservadores da Densidade Óssea/uso terapêutico , Denosumab , Feminino , Seguimentos , Marcadores Genéticos , Humanos , Transplante de Rim/efeitos adversos , Masculino , Pessoa de Meia-Idade , Osteoporose/etiologia , Osteoporose/prevenção & controle , Estudos Prospectivos , Insuficiência Renal Crônica/metabolismo , Insuficiência Renal Crônica/cirurgia , Resultado do Tratamento
8.
Surg Today ; 44(4): 626-32, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23459787

RESUMO

PURPOSE: Poor arterial inflow during orthotopic liver transplantation (OLT) may necessitate arterial revascularisation using aorto-hepatic bypasses with supraceliac (SC) or infrarenal (IR) allografts. This study compared both techniques focusing on the patients' preoperative conditions, postoperative graft/organ function, complications and survival. METHODS: Fifteen out of 114 OLT patients underwent revascularisation (7 IR/8 SC) between 2005 and 2008 and were included in the study. The patients' records were reviewed retrospectively. RESULTS: IR patients presented with a higher BMI, received more male donor organs and their reperfusion sequence was predominately portal venous (SC: primary arterial). SC patients presented a significantly worse preoperative creatinine clearance and a trend towards a higher MELD score. The postoperative graft/organ function, morbidity and mortality did not differ between the groups despite a trend towards a worse survival in the SC group. A deteriorated preoperative creatinine clearance and higher MELD score negatively impacted the survival. Postoperative bleeding episodes and major re-interventions also affected the outcome. CONCLUSIONS: We found no evidence for superiority of either bypass technique in our OLT patients. The trend toward a worse survival in SC patients was most likely caused by the worse preoperative conditions of these patients and highlights the importance of the impact of the MELD score on the outcome after OLT.


Assuntos
Aorta/cirurgia , Artéria Hepática/cirurgia , Transplante de Fígado/mortalidade , Transplante de Fígado/métodos , Índice de Gravidade de Doença , Adulto , Implante de Prótese Vascular/métodos , Índice de Massa Corporal , Feminino , Sobrevivência de Enxerto , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Taxa de Sobrevida
9.
Transpl Int ; 26(1): 30-3, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23072376

RESUMO

Combined pancreas and kidney transplantation is the therapy of choice for type I diabetes patients with associated end-stage renal disease. To counterbalance increasing waiting lists, there is a clear need to extend the organ donor pool. Although results following simultaneous pancreas and kidney transplantation (SPK) using pediatric organs are encouraging, there is still reluctance in accepting them. This reflects the fear of graft thrombosis and graft failure because of small vessels and little absolute islet cell mass. Simpler transplant techniques for pediatric SPK might lower this threshold. In this article, a novel technique using a "piggy-back" implantation of the pancreas onto the conduits of en-bloc grafted kidneys, performed in two consecutive cases, is presented. This technique is associated with less vascular manipulation, requiring only one arterial anastomosis onto the frequently arteriosclerotic arteries of the recipient for all three organs. One-year follow-up (14 and 12 months) proved excellent graft function of kidneys and pancreas.


Assuntos
Transplante de Rim/métodos , Transplante de Pâncreas/métodos , Adulto , Criança , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Obtenção de Tecidos e Órgãos
10.
Ann Transplant ; 28: e938692, 2023 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-37157234

RESUMO

BACKGROUND Access to kidney transplantation is limited for elderly patients with end-stage renal disease (ESRD), who often die while on the waiting list or receive kidneys from marginal deceased donors. In our transplantation center, most donated kidneys were from younger living relatives, in whom donations to elderly outcomes were not previously studied. In this study, we aimed to determine the short- and long-term outcomes of patients aged ³65 years to justify the use of kidneys from younger donors in older recipients. We also compared the outcomes between those who received kidneys from living donors (LDs) and deceased donors (DDs). MATERIAL AND METHODS We analyzed the patients' demographic data and the 1-, 5-, and 10-year patient and graft survival rates of patients aged ≥65 years who received kidney transplants between January 2005 and December 2020. RESULTS Among 158 patients, 136 received kidneys from LD and 22 from DD. The mean age was 69 years old. In this cohort, the most common cause of ESRD was diabetes. The graft survival rates were 99%, 96%, and 94% after 1, 5, and 10 years, respectively. Patient survival was 94%, 83%, and 61% after 1, 5, and 10 years, respectively. Delayed graft function rates, 1-year patient survival, and 5- and 10-year graft survival rates were lower in the DD group. Ischemic heart disease and transplantation from DD were independent risk factors for mortality. CONCLUSIONS Our study demonstrated reasonably good patient and graft survival rates in older patients. Outcomes were better in patients who received kidneys from LD.


Assuntos
Falência Renal Crônica , Transplante de Rim , Idoso , Humanos , Transplante de Rim/efeitos adversos , Sobrevivência de Enxerto , Doadores de Tecidos , Doadores Vivos , Falência Renal Crônica/cirurgia , Falência Renal Crônica/etiologia , Fatores de Risco , Rim , Resultado do Tratamento
11.
Hepatol Commun ; 7(10)2023 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-37755878

RESUMO

BACKGROUND: Graft-versus-host disease following liver transplantation is a serious and usually fatal complication. Data identifying the risk factors and specifying the diagnosis and treatment options of the disease are scarce and contentious. Moreover, recommendations for therapeutic approaches are similarly sparse. METHODS: A systematic review of the literature from 1988 to 2020 on graft-versus-host disease following liver transplantation was performed using the PubMed and MEDLINE databases. Medical subject headings, such as graft-versus-host disease and GvHD were used in combination with solid organ transplant, transplantation, or liver transplant. Following duplicate removal, 9298 articles were screened for suitability. A total of 238 full-text articles were analyzed for eligibility, resulting in 130 eligible articles for meta-analysis. Two hundred twenty-five patients developing graft-versus-host disease following liver transplantation reported herein were mainly published in case reports and case series. RESULTS: Graft-versus-host disease occurred with an incidence of 1.2%. 85% developed following deceased donor liver transplant and 15% following living-related donor liver transplantation. The median follow-up period following liver transplantation was 84 days (interquartile range, 45-180). The median time from liver transplantation to graft-versus-host disease onset was 30 days (interquartile range, 21-42). The main clinical features included skin rash (59%), fever (43%), diarrhea (36%), and pancytopenia (30%). The overall mortality rate was 71%. Neither univariate (HR = 0.999; 95% CI, 0.493-2.023; p = 1.0) nor multivariate Cox regression analysis revealed a significant correlation between adaptation of immunosuppression and survival probability (HR = 1.475; 95% CI, 0.659-3.303; p = 0.3). CONCLUSIONS: This systematic review suggests that an increase in immunosuppressive regimen does not yield any survival benefit in patients suffering from graft-versus-host disease following liver transplantation.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Fígado , Humanos , Transplante de Fígado/efeitos adversos , Doadores Vivos , Doença Enxerto-Hospedeiro/diagnóstico , Doença Enxerto-Hospedeiro/etiologia , Imunossupressores/efeitos adversos , Fatores de Risco
13.
Clin Transplant ; 26(3): 387-92, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-21980989

RESUMO

The risk of progression to renal replacement after pancreas transplant alone (PTA) is a concern in patients with pre-transplant estimated glomerular filtration rate (eGFR) < 70 mL/min/1.73 m(2). This is a retrospective, single-center risk analysis of potential factors affecting renal function after PTA. Twenty-four patients, transplanted over a three-yr period, with functioning pancreatic grafts at the study's end point were included. High tacrolimus levels (> 12 mg/dL) at six months post-transplant was the only independent risk factor identifying a substantial decline in native renal function by Cox regression analysis (HR = 14.300, CI = 1.271-160.907, p = 0.031). The presence of severe pre-transplant proteinuria (urine Pr/Cr ≥ 100 mg/mmol) marginally failed to reach significance (p = 0.056). Low eGFR levels alone (≤ 45 and ≤ 40 mL/min/1.73 m(2)) at the time of transplant did not correlate with substantial decline in renal function. Our data suggest that PTA is a justifiable therapy for patients with hypoglycemia unawareness or other life-threatening diabetic complications, even in those with borderline renal function, provided that they do not suffer from severe proteinuria and appropriate monitoring and tailoring of immunosuppression is ensured.


Assuntos
Transplante de Pâncreas/efeitos adversos , Transplante de Pâncreas/mortalidade , Insuficiência Renal/etiologia , Insuficiência Renal/mortalidade , Adulto , Feminino , Seguimentos , Taxa de Filtração Glomerular , Humanos , Masculino , Prognóstico , Insuficiência Renal/diagnóstico , Estudos Retrospectivos , Medição de Risco , Taxa de Sobrevida
14.
Transpl Int ; 25(4): 416-23, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22320241

RESUMO

Early conversion to a calcineurin-inhibitor (CNI)-free maintenance immunosuppression with sirolimus (SRL), mycophenolate mofetil (MMF) and steroids was associated with an improved 1-year renal function as compared with a cyclosporine (CsA)-based regimen (SMART core-study). This observational follow-up describes 132 patients followed up within the SMART study framework for 36months. At 36months, renal function continued to be superior in SRL-treated patients [ITT-eGFR(@36m) : 60.88 vs. 53.72 (CsA) ml/min/1.73m(2) , P=0.031]. However, significantly more patients discontinued therapy in the SRL group 59.4% vs.42.3% (CsA). Patient [99% (SRL) vs.97% (CsA) and graft 96% (SRL) vs.94% (CsA)] survival at 36months was excellent in both arms. There was no difference in late rejection episodes. Late infections and adverse events were similar in both arms except of a higher rate of hyperlipidemia in SRL and a higher incidence of malignancy in CsA-treated patients. In a multivariate analysis, donor age >60years, S-creatinine at conversion >2mg/dl, CMV naïve(-) recipients and immunosuppression with CsA were predictive of an impaired renal function at 36months. Early conversion to a CNI-free SRL-based immunosuppression is associated with a sustained improvement of renal function up to 36months after transplantation. Patient selection will be key to derive long-term benefit and avoid treatment failure using this mTOR-inhibitor-based immunosuppressive regimen.


Assuntos
Inibidores de Calcineurina , Terapia de Imunossupressão/métodos , Transplante de Rim/fisiologia , Sirolimo/administração & dosagem , Creatinina/sangue , Ciclosporina/administração & dosagem , Feminino , Seguimentos , Rejeição de Enxerto/epidemiologia , Humanos , Imunossupressores/efeitos adversos , Transplante de Rim/efeitos adversos , Masculino , Pessoa de Meia-Idade , Ácido Micofenólico/análogos & derivados , Serina-Treonina Quinases TOR/antagonistas & inibidores
15.
Chirurg ; 93(2): 205-214, 2022 Feb.
Artigo em Alemão | MEDLINE | ID: mdl-34264370

RESUMO

The term intestinal failure (IF) is understood as the transient or irreversible loss of the resorptive capacity of the bowels. This includes a multitude of diseases, some of which have anatomical causes and others functional causes. The functional capacity (absorption and motility) of the remaining digestive tract and the bacterial overgrowth and false colonization of the small bowel are of prognostic importance. After exclusion of pathological intestinal findings, such as stenosis and dilatation, initially conservative treatment is employed with the aim of intestinal adaptation. Before failure or complications, initially conservative surgery and then organ replacement by transplantation should be considered. The IF is a temporary or permanent condition. For adults a length of 100cm small bowel without the colon, 60cm still with continuity to the colon and 35cm small bowel with complete preservation of the colon including the ileocecal valve are potentially sufficient for intestinal autonomy.


Assuntos
Insuficiência Intestinal , Síndrome do Intestino Curto , Adaptação Fisiológica , Adulto , Humanos , Intestino Delgado/cirurgia , Intestinos
16.
J Clin Med ; 11(13)2022 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-35807185

RESUMO

In liver transplantation, older donor age is a well-known risk factor for dismal outcomes, especially due to the high susceptibility of older grafts to ischemia-reperfusion injury. However, whether the factors correlating with impaired graft and patient survival following the transplantation of older grafts follow a linear trend among elderly donors remains elusive. In this study, liver transplantations between January 2006 and May 2018 were analyzed retrospectively. Ninety-two recipients of grafts from donors ≥65 years were identified and divided into two groups: (1) ≥65-69 and (2) ≥ 70 years. One-year patient survival was comparable between recipients of grafts from donors ≥65-69 and ≥70 years (78.9% and 70.0%). One-year graft survival was 73.1% (donor ≥65-69) and 62.5% (donor ≥ 70), while multivariate analysis revealed superior one-year graft survival to be associated with a donor age of ≥65-69. No statistically significant differences were found for rates of primary non-function. The influence of donor age on graft and patient survival appears not to have a distinct impact on dismal outcomes in the range of 65-70 years. The impact of old donor age needs to be balanced with other risk factors, as these donors provide grafts that offer a lifesaving graft function.

17.
Cells ; 11(6)2022 03 10.
Artigo em Inglês | MEDLINE | ID: mdl-35326400

RESUMO

Ischemia reperfusion injury (IRI) is a form of sterile inflammation whose severity determines short- and long-term graft fates in kidney transplantation. Neutrophils are now recognized as a key cell type mediating early graft injury, which activates further innate immune responses and intensifies acquired immunity and alloimmunity. Since the macrolide Bryostatin-1 has been shown to block neutrophil transmigration, we aimed to determine whether these findings could be translated to the field of kidney transplantation. To study the effects of Bryostatin-1 on ischemia-elicited neutrophil transmigration, an in vitro model of hypoxia and normoxia was equipped with human endothelial cells and neutrophils. To translate these findings, a porcine renal autotransplantation model with eight hours of reperfusion was used to study neutrophil infiltration in vivo. Graft-specific treatment using Bryostatin-1 (100 nM) was applied during static cold storage. Bryostatin-1 dose-dependently blocked neutrophil activation and transmigration over ischemically challenged endothelial cell monolayers. When applied to porcine renal autografts, Bryostatin-1 reduced neutrophil graft infiltration, attenuated histological and ultrastructural damage, and improved renal function. Our novel findings demonstrate that Bryostatin-1 is a promising pharmacological candidate for graft-specific treatment in kidney transplantation, as it provides protection by blocking neutrophil infiltration and attenuating functional graft injury.


Assuntos
Transplante de Rim , Traumatismo por Reperfusão , Animais , Briostatinas/farmacologia , Células Endoteliais/metabolismo , Isquemia/tratamento farmacológico , Transplante de Rim/efeitos adversos , Neutrófilos/metabolismo , Traumatismo por Reperfusão/metabolismo , Suínos
18.
Ann Hepatol ; 10(3): 355-60, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21677340

RESUMO

The increasing demand for transplantation has led to consideration of liver grafts from donors exposed to hepatitis B virus (HBV). Six transplantations of liver grafts from hepatitis B surface antigen (HBsAg) positive donors have been reported; two recipients suffered from HBV/HDV (hepatitis Delta virus) coinfection and were followed up for 10-12 months. Here, we report a 56 months follow-up of a HBV/HDV-coinfected recipient of a HBsAg positive liver graft. Posttransplant combination prophylaxis consisted of hepatitis immunoglobulin, lamivudine and adefovir dipivoxil. HBsAg remained positive during stable posttransplant follow-up and subclinical HDV reinfection with low replication rate was detected at 1 month. Pegylated interferon therapy was introduced after documentation of histological evidence of mild chronic hepatitis, but without virological response after 48 weeks. Finally, antiviral treatment was switched to tenofovir disoproxil fumarate. More than 50 months posttransplant the recipient revealed clinical symptoms of decompensated liver cirrhosis and has been relisted for liver transplantation. In conclusion HBsAg positive liver grafts in HBsAg positive recipients with HDV coinfection may result in virological recurrence and rapid development of liver cirrhosis.


Assuntos
Antígenos de Superfície da Hepatite B/metabolismo , Hepatite B/cirurgia , Hepatite D/cirurgia , Transplante de Fígado/efeitos adversos , Fígado/imunologia , Comorbidade , Vírus da Hepatite B/isolamento & purificação , Vírus Delta da Hepatite/isolamento & purificação , Humanos , Fígado/virologia , Cirrose Hepática/etiologia , Transplante de Fígado/imunologia , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
19.
J Clin Med ; 10(11)2021 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-34071904

RESUMO

Organ scarcity demands critical decision-making regarding eligible transplant candidates and graft allocation to ensure best benefit from renal transplantation (RTx). Among the controversial relative contraindications is a history of pretransplant malignancy (PTM). While oncological outcomes of PTM-RTx recipients are well described, data on graft-specific outcome are scarce. A retrospective double case control matched pair analysis (60 months follow-up) was carried out and RTx-recipients were stratified for history of PTM. First, PTM-RTx recipients were matched according to age, sex and duration of immunosuppressive therapy. Next, PTM-RTx recipients were matched 1:1 for age, sex and cause of end-stage renal disease. Five-year patient and graft survival as well as oncological outcomes were analyzed. A total of 65 PTM-RTx recipients were identified. Post-RTx recurrence rate was 5%, while 20% developed second de novo malignancy, comparable to 14% in the control group. PTM-RTx recipients had a noticeable lower five-year death-censored as well as overall graft survival and Cox proportional hazard modeling showed a correlation between PTM and inferior graft survival. Although underlying reasons remain not fully understood, this study is the first to show inferior graft survival in PTM-RTx recipients and advocates necessity to focus on more meticulous graft monitoring in PTM recipients in addition to heightened surveillance for cancer recurrence.

20.
Ann Transplant ; 26: e926847, 2021 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-33602890

RESUMO

BACKGROUND Although most centers perform primary portal vein reperfusion (PV) in orthotopic liver transplantation (OLT) for historical reasons, there is so far no sound evidence as to whether this technique is superior. The present study evaluated the long-term outcome of 3 different reperfusion sequences: PV vs primary arterial (A) vs simultaneous reperfusion (SIM). MATERIAL AND METHODS All patients at our center who underwent OLT (who received a primary, whole-organ liver graft) from 2006 to 2007 were evaluated for analysis. RESULTS A total of 61 patients were found eligible (PV: 25, A: 22, SIM: 14). Twenty-one patients (35%) were still alive after the follow-up period of 12 years. Despite poorer starting conditions such as higher recipient age (59 y (SIM) vs 55 y (A) vs 50 y (PV), P=0.01) and donor age (56 y (SIM) vs 51 y (PV) vs 50 y (A), n.s.), higher MELD scores (22 vs 19 (PV) vs 17 (A), n.s.), as well as a higher number of marginal donor organs (79% (SIM) vs 36% (A/PV), P=0.02), SIM-recipients demonstrated superior outcomes. Overall survival was 8.1 y (SIM), 4.8 y (PV), and 5.9 y (A, n.s.)). None of the SIM-recipients underwent re-transplantation, while the rate was 32% in the PV-group. The 8.1 y graft survival in SIM-recipients was significantly longer than in the other 2 groups, which were 3.3 y (PV) and 5.5 y (A, P=0.013). CONCLUSIONS Although SIM-reperfused recipients were the oldest and received grafts of inferior quality, these recipients showed superior results in terms of overall patient and graft survival. Multicentric randomized controlled trials with larger study populations are required to confirm this finding.


Assuntos
Transplante de Fígado , Reperfusão/métodos , Adulto , Idoso , Carcinoma Hepatocelular , Doença Hepática Terminal/cirurgia , Feminino , Sobrevivência de Enxerto , Humanos , Neoplasias Hepáticas , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Índice de Gravidade de Doença
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