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Current opinion in organ transplantation [journal]
- Liver transplantation: immunosuppression and oncology. [JOURNAL ARTICLE]
- Curr Opin Organ Transplant 2014 Mar 28.
Long-term survival of liver transplant recipients is threatened by increased rates of de-novo malignancy and recurrence of hepatocellular carcinoma (HCC), both events tightly related to immunosuppression.There is accumulating evidence linking increased exposure to immunosuppressants and carcinogenesis, particularly concerning calcineurin inhibitors (CNIs), azathioprine and antilymphocyte agents. A recent study including 219 HCC transplanted patients showed that HCC recurrence rates were halved if a minimization of CNIs was applied within the first month after liver transplant. With mammalian target of rapamycin (mTOR) inhibitors as approved immunosuppressants for liver transplant patients, pooled data from several retrospective studies have suggested their possible benefit for reducing HCC recurrence.Randomized controlled trials with sufficiently long follow-up are needed to evaluate the influence of different immunosuppression protocols in preventing malignancy after LT. Currently, early minimization of CNIs with or without mTOR inhibitors or mycophenolate seems a rational strategy for patients with risk factors for de-novo malignancy or recurrence of HCC after liver transplant. A deeper understanding of the immunological pathways of rejection and cancer would allow for designing more specific and safer drugs, and thus to prevent cancer after liver transplant.This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivitives 3.0 License, where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially. http://creativecommons.org/licenses/by-nc-nd/3.0.
- Editorial introductions. [Journal Article]
- Curr Opin Organ Transplant 2014 Apr; 19(2):v-vi.
- Ethical dilemmas in psychiatric evaluations in patients with fulminant liver failure. [Journal Article]
- Curr Opin Organ Transplant 2014 Apr; 19(2):175-80.
Fulminant hepatic failure (FHF) is one of the more dramatic and challenging syndromes in clinical medicine. Time constraints and the scarcity of organs complicate the evaluation process in the case of patients presenting with FHF, raising ethical questions related to fairness and justice. The challenges are compounded by an absence of standardized guidelines.Acetaminophen overdose, often occurring in patients with histories of psychiatric illness and substance dependence, has emerged as the most common cause of FHF. The weak correlations between psychosocial factors and nonadherence, as per some studies, suggest that adherence may be influenced by systematic factors. Most research suggests that applying rigid ethical parameters in these patients, rather than allowing for case-dependent flexibility, can be problematic.The decision to transplant in patients with FHF has to be made in a very narrow window of time. The time-constrained process is fraught with uncertainties and limitations, given the absence of patient interview, fluctuating medical eligibility, and limited data. Although standardized scales exist, their benefit in such settings appears limited. Predicting compliance with posttransplant medical regimens is difficult to assess and raises the question of prospective studies to monitor compliance.
- T cells in organ ischemia reperfusion injury. [Journal Article]
- Curr Opin Organ Transplant 2014 Apr; 19(2):115-20.
Ischemia and reperfusion injuries occur in multiple clinical settings and contribute to organ dysfunction/failures. Despite the innate inflammatory immune nature, T cells that are critically involved in the pathogenesis of ischemia reperfusion injury (IRI), include not only CD4 T cells, but also CD8 and γδT cells. This review focuses on questions of how putative Ag-specific T cells are involved, which include whether they function in an Ag-dependent manner; how they function, cytokine-mediated or costimulatory molecule-mediated mechanisms; and whether different T-cell subsets, Th1, Th17, regulatory T cell (Treg), are all involved and play distinctive roles?Specific T-cell populations, such as effector memory CD4 T cells, promote inflammatory immune activation by ischemia reperfusion independent of their adaptive properties, that is Ag-independently. They function by secreting cytokines and expressing costimulatory molecules to either promote or inhibit innate immune activation, or facilitate tissue repair/homeostasis, as exemplified by Th1, Th17 or Th2, Treg cells, respectively.T-cell-targeted therapies need to be refined with strategies to maximally eliminate the proinflammatory but spare the anti-inflammatory/immune regulatory properties of T cells, for future clinical application to ameliorate IRI.
- Procurement for visceral organ transplantation: where to cannulate and how to perfuse? [Journal Article]
- Curr Opin Organ Transplant 2014 Apr; 19(2):92-9.
Despite significant improvements in visceral organ transplantation over the last few decades, some technical aspects of organ harvesting remain controversial. The purpose of this article is to review and summarize the latest literature on how to perfuse in multiorgan procurement.Few prospective studies have analyzed and compared technical aspects of harvesting such as cannulation (aortic-only versus dual aortic and portal flush), flush rates and volumes as well as flush pressures (high pressure vs. gravity). However, these and most data available from additional retrospective and experimental studies do not clearly support one harvesting technique over another.Currently, because of lack of superiority data, no clear guidelines exist on what cannulation techniques to apply during organ procurements in visceral organ transplantation. Additional prospective trials are needed to clarify these questions.
- Impact of brain death on ischemia/reperfusion injury in liver transplantation. [Journal Article]
- Curr Opin Organ Transplant 2014 Apr; 19(2):108-14.
In liver transplantation, the ischemia/reperfusion injury (IRI) is influenced by factors related to graft quality, organ procurement and the transplant procedure itself. However, in brain-dead donors, the process of death itself also thoroughly affects organ damage through breakdown of the autonomous nervous system and subsequent massive cytokine release. This review highlights the actual knowledge on these proinflammatory effects of brain death on IRI in liver transplantation.Brain death affects IRI either through hemodynamical or molecular effects with proinflammatory activation. Immunological effects are mainly mediated through Kupffer cell activation, leading to TNF-α and TLR4 amplification. Proinflammatory cytokines such as interleukin (IL)-6, IL-10, TNF-β and MIP-1α are released, together with activation of the innate immune system via natural killer cells and natural killer T cells, which promote organ damage and activation of fibrosis. Preprocurement treatment regimens attempt to hamper inflammatory response by the application of methylprednisolone or thymoglobulin to the donor. Selective P-selectin antagonism resulted in improved function in marginal liver grafts. Inhaled nitric oxide was found to reduce apoptosis in liver grafts. Other medications like the immunosuppressant tacrolimus produced conflicting results regarding organ protection. Furthermore, improved organ storage after procurement - such as machine perfusion - can diminish effects of IRI in a clinical setting.Brain death plays a fundamental role in the regulation of molecular markers triggering inflammation and IRI-related tissue damage in liver transplants. Although several treatment options have reached clinical application, to date, the effects of brain death during donor conditioning and organ procurement remain relevant for organ function and survival.
- Ethics of facial transplantation revisited. [Journal Article]
- Curr Opin Organ Transplant 2014 Apr; 19(2):181-7.
There have been 26 cases of facial transplantation reported, and three deaths, 11.5%. Mortality raises the issue of risk versus benefit for face transplantation, a procedure intended to improve quality of life, rather than saving life. Thus, one of the most innovative surgical procedures has opened the debate on the ethical, legal, and philosophical aspects of face transplantation.Morbidity in face transplant recipients includes infections and metabolic consequences. No graft loss caused by technical failure, hyperacute, or chronic graft rejection or graft-versus-host disease has been reported. One case of posttransplant lymphoproliferative disorder, 3.45% and one case of lymphoma in an HIV-positive recipient were reported. Psychological issues in candidates can include chronic pain, mood disorders, preexisting psychotic disorders, post-traumatic stress disorder (PTSD), and substance abuse.Early publications on ethical aspects of face transplantation focused mainly on informed consent. Many other ethical issues have been identified, including lack of coercion, donor family consent and confidentiality, respect for the integrity of the donor's body, and financial promotion of the recipient and transplant team, as well as the cost to society for such a highly technical procedure, requiring lifelong immunosuppression.
- Organ procurement and preservation: what is new and what is established? [Journal Article]
- Curr Opin Organ Transplant 2014 Apr; 19(2):83-4.
- Underpinnings of cellular organ replacement therapies. [Journal Article]
- Curr Opin Organ Transplant 2014 Apr; 19(2):131-2.
- Organ protection in allograft recipients: anesthetic strategies to reduce postoperative morbidity and mortality. [Journal Article]
- Curr Opin Organ Transplant 2014 Apr; 19(2):121-30.
Organ protection remains a primary objective in the anesthetic management of patients undergoing transplantation. An ongoing effort has been made to develop strategies to improve graft outcome and reduce postoperative morbidity and mortality, but trials have reported conflicting results. The aim of this review was to provide a comprehensive summary of the anesthetic management in transplant recipients and to identify current strategies for organ protection.Decreasing blood products requirements, intraoperative blood glucose control and adequate postoperative pain therapy may improve patient outcome. Vasopressors have been reported to reduce perioperative bleeding but might be associated with postoperative acute renal failure in liver transplantation. Early extubation may increase survival rates in recipients. These perioperative challenges, along with other protective strategies, have been addressed in 20 recently published studies: 10 randomized controlled trials, nine retrospective studies and one prospective study.This review identified several promising strategies ensuring organ protection and improving patient outcome after solid organ transplantation. However, as outcomes were difficult to compare, further evidence will be needed before drawing firm conclusions.