Safety and Outcomes in 100 Consecutive Donation After Circulatory Death Liver Transplants Using a Protocol That Includes Thrombolytic Therapy.

Donation after circulatory death (DCD) liver transplantation (LT) reportedly yields inferior survival and increased complication rates compared with donation after brain death (DBD). We compare 100 consecutive DCD LT using a protocol that includes thrombolytic therapy (late DCD group) to an historical DCD group (early DCD group n = 38) and a cohort of DBD LT recipients (DBD group n = 435). Late DCD LT recipients had better 1- and 3-year graft survival rates than early DCD LT recipients (92% vs. 76.3%, p = 0.03 and 91.4% vs. 73.7%, p = 0.01). Late DCD graft survival rates were comparable to those of the DBD group (92% vs. 93.3%, p = 0.24 and 91.4% vs. 88.2%, p = 0.62). Re-transplantation occurred in 18.4% versus 1% for the early and late DCD groups, respectively (p = 0.001). Patient survival was similar in all three groups. Ischemic-type biliary lesions (ITBL) occurred in 5%, 3%, and 0.2% for early DCD, late DCD, and DBD groups, respectively, but unlike in the early DCD group, in the late DCD group ITBL was endoscopically managed and resolved in each case. Using a protocol that includes a thrombolytic therapy, DCD LT yielded patient and graft survival rates comparable to DBD LT.

Anonymous living liver donation: donor profiles and outcomes.

There are no published series of the assessment process, profiles and outcomes of anonymous, directed or nondirected live liver donation. The outcomes of 29 consecutive potential anonymous liver donors at our center were assessed. We used our standard live liver assessment process, augmented with the following additional acceptance criteria: a logical rationale for donation, a history of social altruism, strong social supports and a willingness to maintain confidentiality of patient information. Seventeen potential donors were rejected and 12 donors were ultimately accepted (six male, six female). All donors were strongly motivated by a desire and sense of responsibility to help others. Four donations were directed toward recipients who undertook media appeals. The donor operations included five left lateral segmentectomies and seven right hepatectomies. The overall donor morbidity was 40% with one patient having a transient Clavien level 3 complication (a pneumothorax). All donors are currently well. None expressed regret about their decision to donate, and all volunteered the opinion that donation had improved their lives. The standard live liver donor assessment process plus our additional requirements appears to provide a robust assessment process for the selection of anonymous live liver donors. Acceptance of anonymous donors enlarges the donor liver pool.

Acute humoral rejection in an ABO compatible combined liver-kidney transplant--the kidney is not always protected.

Combined liver-kidney transplantation has become a common practice for the treatment of patients with concurrent end-stage renal disease and end-stage liver disease. Liver transplantation in the setting of multiorgan transplantation is thought to have a protective effect against humoral rejection even when a positive crossmatch is obtained prior to surgery. In most centers, a pre liver-kidney transplant crossmatch is rarely performed because of the known immunoprotective effect of the liver allograft. In this report, a case of acute humoral rejection in the kidney allograft after a combined liver-kidney transplant is described. Although humoral rejection was treated using plasmapheresis, intravenous immunoglobulin and rituximab, the kidney required 3 months to recover function and finally progressed to chronic allograft nephropathy. A heightened index of suspicion for acute humoral rejection of the renal allograft is necessary when performing combined liver-kidney transplants to highly sensitized patients due to previous organ transplants.

Downregulation of telomerase activity in HL60 cells by differentiating agents is accompanied by increased expression of telomerase-associated protein.

Telomerase activity provides a mechanism for the unlimited division potential of neoplastic cells. Induced differentiation of these cells was found to be associated with repression of telomerase activity irrespective of the inducing agent. We have employed a series of sublines of human promyelocytic leukemia line HL60 with differing degrees of resistance to differentiation to determine how tightly the expression of the differentiated phenotype is coupled to the downregulation of telomerase activity and to the expression of the recently identified telomerase-associated protein 1 (TP1). As expected, in the 1,25D3-dihydroxyvitamin D3 (1,25D3)-resistant subclones (20A-100A cells), telomerase activity was not significantly downregulated by 1,25D3 and, in most cases, by all-trans retinoic acid (atRA), to which these cells were cross-resistant, but telomerase activity was repressed by dimethylsulfoxide (DMSO) and phorbol-12-myristate-13-acetate (TPA), to which the sublines were in general sensitive. However, there were exceptions; in some instances telomerase activity was repressed in the absence of the expression of markers of differentiation. Also, there was an inverse relationship between telomerase activity and the cellular levels of TP1 transcripts. We conclude that in HL60 cells downregulation of telomerase is loosely associated with upregulation of differentiation markers and with other cellular changes which include an upregulation of TP1.