Organ Transplantation In Japan Research Articles

Current status of generic immunosuppressive drugs for organ transplantation in Japan

Current status of generic immunosuppressive drugs for organ transplantation in Japan

The Ethical Acceptability of a Recipient's Choice of Donor in Directed and Nondirected Transplantation: Japanese Perspective.

In organ transplantation, there is a lack of ethical discussion about the recipient's right not to receive a transplant. Using the current situation of living organ transplantation and deceased organ transplantation in Japan as an example, we prospectively discussed to what extent the recipient's right not to receive a transplant is ethically acceptable. In directed transplantation from a living donor, a recipient may refuse organ donation from a particular donor. It is preferable that a recipient's request for organ donation from a donor occurs as part of a transparent process. In nondirected transplantation from a deceased donor, refusal of transplantation from a particular type of donor appears potentially justifiable. There are both moral and pragmatic considerations. Certain refusals based solely on belief are morally unacceptable, and refusal to transplant a recipient based on the donor's age jeopardizes the entire transplant system. When religious beliefs affect mental and physical health, individualized measures are required for transplant rejection. We also deductively developed a prospective argument based on the current status of donor-recipient communication in living organ transplantation in Japan and the 2010 amendment of the law allowing relatives to be given priority in organ transplantation from deceased donors.

委員会報告：脳死下臓器提供におけるアンケート調査(Surveillance of organ transplantation in Japan with consideration of transfer for the diagnosis of brain death)

要旨新型コロナウイルス感染症蔓延下において脳死下臓器提供数が減少しているなかで，脳死判定を目的とした転院搬送の是非に関する議論が始まっている。これをふまえ，全国救命センターにおけるコロナ禍での脳死判定や脳死下臓器移植に関わる現状と問題点を調査した。全国救命センター295施設に質問紙URLを送付し電子的に回収した。調査項目は施設背景，臓器提供の意思決定に関する質問，臓器提供も見据えた患者管理，脳死判定，臓器提供手術の問題点に関する質問，臓器提供を目的とした転院に関する質問とした。220施設より回答を得た（回答率74.6%）。コロナ禍において臓器提供を施行した施設は45施設（20.5%）存在した。臓器提供を行った施設とそうでなかった施設において，休日夜間帯に勤務をしている専門医数に差が見られた（平均3.04人 対 2.44人）。また，コロナ禍によって臓器提供に関する事項が影響を受けたと回答した施設は全国救命センターの43施設（19.6%）に及び，患者個室管理，家族の面会制限，チームの参集困難など，感染対策による影響と回答した施設がうち39施設（90.7%）に見られた。「脳死下臓器提供」を目的とした転院に関し，他施設に転送したいと回答した施設群（60施設：27%）は，院内連携が手薄く，マンパワーが少なく，また，脳死判定医が少ないこと，脳死判定の費用に関わる経済的問題に要因があると思われた。本研究によりコロナ禍における脳死下臓器提供に関わるハード，ソフト両面の課題が明確になった。とくに施設におけるマンパワー拡充のための施設間連携と経済的支援の拡充が今後の課題であると思われた。

Establishment of standard protocol for packaging organs in organ transplantation in Japan

Establishment of standard protocol for packaging organs in organ transplantation in Japan

The Nursing Students’ Perceptions of Organ Transplantation in Japan: Considering The Need for The Education on Organ Transplantation

The Nursing Students’ Perceptions of Organ Transplantation in Japan: Considering The Need for The Education on Organ Transplantation

On the idea of person and the Japanese notion of ningen and its relation to organ transplantation

It is not possible to talk about bioethics without recognizing the plurality inherent in it. In this sense, the notion of person is important due to its multiplicity of possible interpretations depending on its cultural context. This fact is highlighted in the case of organ transplantation in Japan. While there are many critiques against this procedure from scholars in various fields, those that deal with the problem of brain death are especially problematic. This is because the definition of person that is invoked in such debates does not seem to coincide with how the notion of person has been understood in the Japanese tradition. Hence, investigating the Japanese concept of ningen could be helpful in not only partially clarifying some of the attitudes that exist in Japan towards the notion of brain death, but also to illustrate the need to recognize the plurality of views in modern bioethics.

Twenty Years After Enactment of the Organ Transplant Law in Japan: Why Are There Still So Few Deceased Donors?

BackgroundTwenty years have passed since the 1997 enactment of the Organ Transplant Law in Japan, but the number of deceased donors remains extremely low. In this study we examine why deceased donation has continued to remain so infrequent. MethodsThis investigation was a secondary analysis of published data from the Japan Organ Transplant Network, 2016 Fact Book of Organ Transplantation in Japan, and International Registry on Organ Donation and Transplantation. ResultsIn the past 20 years, donation intent declarations, knowledge, and respect for family member's wishes have increased, whereas resistance toward transplantation has decreased. Despite this, the traditional perspective on corpses of gotai manzoku (ie, the soul cannot be put to rest without being physically intact and without defect), the family-centricism, and reward-seeking altruism have not changed much. Living organ transplants have alleviated the organ deficiency somewhat, and the law requiring family consent seems to have contributed to the observed small increase in deceased donors. ConclusionThe number of deceased donors is unlikely to increase suddenly. However, 8 strategies are proposed to increase the number of deceased donors, including: increasing the number of donor procurement coordinators and establishing a training system; increasing the number of organ procurement facilities; creating hub transplant centers and training transplant surgeons; implementing radical reform in public education; reducing workload and improving education of emergency physicians, neurosurgeons, and pediatricians; revisiting the stringent standards of brain-death determination; revisiting the registration process; and considering development of a Japanese version of organ procurement organizations as well as revisions to the Organ Transplant Law. The Japanese government and academic societies must work together to increase the number of deceased donors in Japan.

National survey of de novo malignancy after solid organ transplantation in Japan.

In Japan, there have been no national surveys on the incidence of de novo malignancy after solid organ transplantation, which is one of the leading causes of death in transplant recipients. A questionnaire was distributed to institutions that perform solid organ transplantation in Japan, and clinical information was collected from patients who underwent transplantation between 2001 and 2010 and who exhibited de novo malignancies. Nine thousand two hundred ten solid organ transplants (kidney, 49.9%; liver, 45.9%; heart, 0.9%; lung, 1.2%; pancreas, 1.9%; small intestine, 0.2%) were performed. Four hundred seventy-nine (5.2%) cases of de novo malignancy were identified. The transplanted organs of the patients included the kidney (n = 479, 54.8%), liver (n = 186, 38.8%), heart (n = 5, 0.1%), lung (n = 18, 3.8%), pancreas (n = 9, 1.9%), and small intestine (n = 1, 0.02%). The most common malignancies were post-transplant lymphoproliferative disorder (n = 87) and cancers of the kidney (n = 43), stomach (n = 41), large intestine (n = 41), and lung (n = 36). This is the first national survey of the incidence of de novo malignancy in Japan. Further study is required to identify the risk of de novo malignancy in organ transplant recipients in comparison to the general population, namely the standardized incidence ratio.

Quantitative Survey of Laypersons' Attitudes Toward Organ Transplantation in Japan

BackgroundIn comparison with foreign countries, living-organ transplantations (LOT) have been performed more frequently than dead organ transplants, including brain-dead organ transplantation (BOT) in Japan. This situation has given rise to organ transplantation tourism. Therefore, we clarify laypersons' preferences regarding organ transplantation that are producing the current situation in Japan, to suggest a possible framework for further efforts. MethodsVoluntary completion of a quantitative and anonymous survey was promoted online (a sample size of 1030). The questionnaire had two types of variables concerning demographic characteristics and organ transplantation–related issues. ResultsLOT was favored over BOT. However, for willingness to donate to family members, the participants showed a significantly more positive attitude toward brain-dead organ donors (BODs) than living organ donors (LODs). In the evaluation of each transplantation technology, BOT and LOT were positioned in the middle, between transplantation that does not depend on others and the utilization of animal organs. ConclusionsAlthough LOT was favored over BOT, for participants hypothesized to be in a position to donate and receive organs, BODs received a conversely better reputation than LODs. Our survey and discussion suggest that the present conditions of organ transplantation in Japan might be because there is a lack of deliberation on transplantation tourism and LOT. Therefore, more surveys concerning LOT cases and the implications of avoidance of organs from brain-dead bodies, coupled with more discussions based on these surveys, are necessary to formulate a Japanese transplantation policy for the future.

Lung Transplantation for Lymphangioleiomyomatosis in Japan.

BackgroundLung transplantation has been established as the definitive treatment option for patients with advanced lymphangioleiomyomatosis (LAM). However, the prognosis after registration and the circumstances of lung transplantation with sirolimus therapy have never been reported.MethodsIn this national survey, we analyzed data from 98 LAM patients registered for lung transplantation in the Japan Organ Transplantation Network.ResultsTransplantation was performed in 57 patients as of March 2014. Survival rate was 86.7% at 1 year, 82.5% at 3 years, 73.7% at 5 years, and 73.7% at 10 years. Of the 98 patients, 21 had an inactive status and received sirolimus more frequently than those with an active history (67% vs. 5%, p<0.001). Nine of twelve patients who remained inactive as of March 2014 initiated sirolimus before or while on a waiting list, and remained on sirolimus thereafter. Although the statistical analysis showed no statistically significant difference, the survival rate after registration tended to be better for lung transplant recipients than for those who awaited transplantation (p = 0.053).ConclusionsLung transplantation is a satisfactory therapeutic option for advanced LAM, but the circumstances for pre-transplantation LAM patients are likely to alter with the use of sirolimus.

Perceived burden of nurturing in pediatric organ transplantation in Japan

Perceived burden of nurturing in pediatric organ transplantation in Japan

Situation Surrounding Organ Transplantation: A Comparison Between Spain and Japan

Organ transplantation in Japan, especially from deceased donors, has lagged behind that in other countries for many reasons. Even though the Japanese government approved the revised Organ Transplant Act in 2010, the number of donors remains small and the rate of donation from deceased persons was ranked 61st out of 62 countries registered in the International Registry in Organ Donation and Transplantation December 2014 (http:// www.irodat.org/). On the other hand, Spain has become known as the world-leading country of organ transplantation and set a new world record with 4,360 transplants from 1,682 donors in 2014. The so-called Spanish Model has had a great impact on the development in transplantation in Spain. Here we mention the difference between Spain and our country, Japan, and also how we Japanese can increase donations and improve the situation in our country.

From Cure to Governance: The Biopolitical Scene After the Brain Death Controversy in Japan

This article follows the transformation of discourses and practices concerning organ transplantation in Japan, as well as considers the effect of comparison in dealing with the recent transformations of this medicine. Since the first enactment of the Japanese Organ Transplantation Law in 1997, public interest has shifted from cultural meanings of medicine to governance by numbers. When the Organ Transplantation Law was revised in June 2009, people seemed to be concerned about the number of donations more than ever and tended to pay less attention to the scientific controversy that had surrounded the redefinition of death in Japan since the 1960s. It is fair to say that the discourse about the shortage of organs occupies an increasingly important place in recent debates and serves as a mode of justifying brain death and organ transplantation. There is therefore an urgent need to analyze how the controversy between science and culture has been overcome during these twelve years. What kinds of criteria have been newly employed to justify brain death and promotion of donation? It is now impossible to ignore new kinds of biopolitics if one wants to understand how the human condition has been reconceptualized in recent medical and legal practice. By focusing on the social meaning of the shortage of organs and on the changing arguments justifying organ transplantation, I discuss the biopolitical conjuncture between economies and bodies and argue that, on the emerging biopolitical scene, organ donation and brain death are interpreted through economic practices.

Current Status and Future Aspect of Pediatric Organ Transplantation in Japan after Renewal of Organ Transplantation Law: Great Appreciation to Foreign Donors and Heart Transplant Centers

Children under 15 years of age could not donate their hearts after brain death until the Japanese Organ Transplantation Act was revised on 17th July in 2010, because only persons who had a written consent for organ donation after brain death could donate their organs in Japan. Therefore, small children could not undergo heart transplantation (HTx) in Japan and many Japanese children had been abroad to undergo HTx. After revision of the Act, small children could be able to donate organs if their family accepted and, in fact, two children donated his heart until now. However, no children under 10 years of age donated their organs yet. In this study, the outcomes of pediatric heart transplant candidates were retrospectively reviewed. Patients: 62 Children younger than 18 years old, who was defined as a HTx candidate since the previous Act was issued in 1997, were reviewed. Boys were 35. Age at referral was 6.9 ±5.8 years. Underlying disease was dilated cardiomyopathy (DCM) in 40, restrictive cardiomyopathy (RCM) in 12, hypertrophic cardiomyopahty in 1 and congenital heart disease in 3. 13 pts was implanted with mechanical circulatory support during waiting for HTx (left ventricular assist support (LVAS) in 12 (Centrifugal pump 2, Dura heart 1, NCVC LVAS 8 and Berlin Heart 1) and exctracorporeal membrane oxygenation (ECMO) in 2). 45 were registered in waiting list (Japan in 22, USA in 19 and Germany in 1: Japan and other country in 3). Results: 6 underwent HTx in Osaka University (adult donor 5, child donor 1). 5 were implanted with LVAS and their waiting period was 917 (182 to 1764) days. 23 underwent oversea HTx (Loma Linda 11 (ECMO 1), Columbia 8, Michigan 1, Toronto 1 (LVAS 1) and Bochum 1 (LVAS 1)). Their waiting period for HTx was 51 (16 to 135) days. 5 died during waiting for HTx in Japan and 13 died during preparing to go abroad. 2 HTx recipients died before returning to Japan (antibody mediated rejection in 1 and MOF in 1). All other 27 HTx recipients (Osaka University 4 and abroad 17) survived for 1 months to 13 years after HTx (a mean 6.1 years). One is working full-time. One married. Twenty four are going to school. Conclusion: Although outcome after HTx was satisfactory, many children died before HTx. Although the Act was revised, no organs were procured from small children yet. We greatly appreciate to foreign donors and HTx centers and really hope to start pediatric HTx from pediatric donors soon.

Evolution of Registry and Tracking System for Organ Transplantation in Japan

Previously, the renal and liver transplantation registry in Japan was enforced yearly using registration and tracking papers only on recipients. The input of all patient data and announcement of statistical analysis to the public required a long time. Following The Declaration of Istanbul 2008, the committees planned to establish new registry and tracking systems for renal and liver transplantations on both recipients and donors. As the first step, for renal transplantation, we established a new registry and tracking system, JARTRE (JApan Renal Transplantation REgistry), using flash (USB) memory in 2009. The recipient and donor data were inputted into the USB memory in the transplantation centers. The memory was collected once a year by the committees with performed at 3 months at 1 year and every year after, the operation. As the second step, for liver transplantation, we established an online registry and tracking system, LITRE-J (LIver Transplantation REgistry in Japan), using the Internet in 2011. The recipient and donor data are inputted online in the centers just after transplantation. The tracking is performed at 3 months, at 1 year and every year after the operation. In 2012, we will convert the JARTRE system to an online registration and tracking system using the Internet like LITRE-J. The advantages of these system are the ease of input, scope of the data, and rapidly for statistical processing. Herein we have reported the details of JARTRE and LITRE-J, as well as the evaluation of the registry and tracking systems for renal and liver transplantation in Japan.

Ethics for Bioengineers

Increasingly, biomedical scientists and engineers are involved in projects, design, or research and development that involve humans or animals. The book presents general concepts on professionalism and the regulation of the profession of engineering, including a discussion on what is ethics and moral conduct, ethical theories and the codes of ethics that are most relevant for engineers. An ethical decision-making process is suggested. Other issues such as conflicts of interest, plagiarism, intellectual property, confidentiality, privacy, fraud, and corruption are presented. General guidelines, the process for obtaining ethics approval from Ethics Review Boards, and the importance of obtaining informed consent from volunteers recruited for studies are presented. A discussion on research with animals is included. Ethical dilemmas focus on reproductive technologies, stem cells, cloning, genetic testing, and designer babies. The book includes a discussion on ethics and the technologies of body enhancement and of regeneration. The importance of assessing the impact of technology on people, society, and on our planet is stressed. Particular attention is given to nanotechnologies, the environment, and issues that pertain to developing countries. Ideas on gender, culture, and ethics focus on how research and access to medical services have, at times, been discriminatory towards women. The cultural aspects focus on organ transplantation in Japan, and a case study of an Aboriginal child in Canada; both examples show the impact that culture can have on how care is provided or accepted. The final section of the book discusses data collection and analysis and offers a guideline for honest reporting of results, avoiding fraud, or unethical approaches. The appendix presents a few case studies where fraud and/or unethical research have occurred. Table of Contents: Introduction to Ethics / Experiments with Human Subjects or Animals / Examples of Ethical Dilemmas in Biomedical Research / Technology and Society / Gender, Culture, and Ethics / Data Collection and Analysis

ARGUMENTS AGAINST PROMOTING ORGAN TRANSPLANTS FROM BRAIN‐DEAD DONORS, AND VIEWS OF CONTEMPORARY JAPANESE ON LIFE AND DEATH

As of 2009, the number of donors in Japan is the lowest among developed countries. On July 13, 2009, Japan's Organ Transplant Law was revised for the first time in 12 years. The revised and old laws differ greatly on four primary points: the definition of death, age requirements for donors, requirements for brain-death determination and organ extraction, and the appropriateness of priority transplants for relatives. In the four months of deliberations in the National Diet before the new law was established, various arguments regarding brain death and organ transplantation were offered. An amazing variety of opinions continue to be offered, even after more than 40 years have elapsed since the first heart organ transplant in Japan. Some are of the opinion that with the passage of the revised law, Japan will finally become capable of performing transplants according to global standards. Contrarily, there are assertions that organ transplants from brain-dead donors are unacceptable because they result in organs being taken from living human beings. Considering the current conditions, we will organize and introduce the arguments for and against organ transplants from brain-dead donors in contemporary Japan. Subsequently, we will discuss the primary arguments against organ transplants from brain-dead donors from the perspective of contemporary Japanese views on life and death. After introducing the recent view that brain death should not be regarded as equivalent to the death of a human being, we would like to probe the deeply-rooted views on life and death upon which it is based.

Current status of organ transplantation in Japan and worldwide

Recent advances in immunosuppressant therapy have dramatically reduced the frequency of acute rejection of organ transplants. Subsequently, the short-term graft survival rate has been improved, and ABO blood type-incompatible and existing anti-HLA antibody-positive kidney transplantation has been enabled, which has increased the availability of living kidney donors. Japan has a unique history and strategies of liver transplantation (LT) for various liver diseases. The outcomes of living donor liver transplantation (LDLT) in Japan is comparable to that of deceased donor liver transplantation (DDLT) in Western countries despite the relatively short history of LT. The main disadvantage of LT in Japan is donor shortage mainly due to the small number of available deceased donors. There are some disadvantages with LDLT in autoimmune liver diseases because of the dependence on blood relative donors. The first brain-dead pancreas transplantation (PTx) was performed in 2000. Since that time, 42 brain-dead PTx, 2 non-heart beating PTx, and 14 living donor PTx had been performed by the end of 2007. One of the 44 recipients of deceased donor PTx died of unknown causes 11 months after transplantation. Although most of the deceased donors in Japan were marginal and their condition was not favorable, the results of these cases were comparable to those of Western countries. Fourteen intestinal transplantations (ITx) had been performed by the end of 2007 in four transplant centers. There were 3 deceased donor and 11 live donor transplants. The original diseases included short bowel syndrome (n = 6), intestinal function disorder (n = 6), and retransplantation (n = 2). The graft and patient survival rate are 60% and 69%, respectively. Eight recipients survived and stopped parenteral nutrition with full-functioning grafts. Amendment of the Japanese law for the utilization of deceased donors should increase the number available donors in the future.

Popularizing Organ Transplantation in Japan: Travelling Iceboxes as the ‘Relay of Life’

In Japan, the ‘relay of life’ has become a common metaphor for organ transplantation. Its prevalence has owed much to the cultural construction of a breakthrough motif vis-à-vis Japan's first legally and publicly accepted transplant case in 1999. The media coverage of this event forged a specific imagery in which the relay of life model and a hopeful breakthrough message were inscribed. This breakthrough motif then developed into the general metaphor for transplant medicine in Japan. Previous research has arguably ascribed the Japanese metaphor to the endeavour, by promoters of transplant medicine, to avoid invoking the Euro–American idea of a transplanted organ as a gift, in a culture that sees gift exchange (including organ transplantation with living donors) as a practice that takes place principally within the personalized network. However, this does not explain the relay metaphor per se, and is therefore an incomplete account. It is necessary to examine the reasons behind the choice of this specific metaphor, what the relay of life actually signifies, and how the metaphor was articulated and distributed. This enquiry illuminates the aforementioned developing process of the relay metaphor, whilst also taking account of the then Japanese public debating discourse about transplant medicine vis-à-vis its metaphoric idiom in the English language, the ‘gift of life’. It demonstrates that the relay metaphor in Japan was not established through the deliberate efforts of those promoting transplantation, but rather was constructed via media coverage of a breakthrough case in 1999.

The Role of Apheresis Therapy for ABO Incompatible Living Donor Liver Transplantation: The Kyoto University Experience

Liver transplantation is a radical surgical therapy for end-stage liver disease. Although in Japan organ transplantation from brain-dead donors (BDD) has been allowed since October 1997, to date, only 29 liver grafts from BDD have been obtained. Thus, most of the liver transplantations carried out use living-donor liver transplantation (LDLT), and BDD liver transplantation is only used in rare cases. In order to carry out LDLT more safely, apheresis (plasmapheresis: PE) plays a major role in our country because of the prevalence of LDLT wherein later re-transplantation is difficult. Thus, because of a limited donor supply and because the needs of patients with end-stage liver disease is critical, use of grafts from ABO-incompatible (ABO-I) donors might be the only available option. From June 1990 to November 2005, 1100 patients underwent 1151 LDLT cases at Kyoto University Hospital. Additionally, 159 LDLT cases (13.8%) received ABO-I living-donor liver grafts. The role of apheresis in ABO-I LDLT is the reduction of antibody titers such as anti-A or anti-B antibody. We carry out preoperative PE as a general rule for ABO-I cases, and the recipient's antibody level against the donor's blood type is decreased to one eighth of the baseline value before LDLT. Until now, baseline immunosuppressive agents included steroids, tacrolimus and cyclophosphamide. At first, splenectomy was carried out during surgery to suppress antibody production, and intraportal (PV) infusion therapy was carried out to control local disseminated intravascular coagulation (DIC) occurring in ABO-I grafts. At that time, three drugs-methylprednisolone, prostaglandin E1 (PGE1), and gabexate mesylate (FOY) were infused continuously for 3 weeks after LDLT. At present, instead of PV infusion therapy, hepatic artery infusion therapy without splenectomy is adopted because of portal thrombosis, and two drugs- methylprednisolone and PGE1- are infused continuously for 3 weeks following LDLT. Recently, we introduced anti-CD20 monoclonal antibody (Rituximab) instead of splenectomy for B cell deletion before ABO-I LDLT. In the present article, we describe the role of apheresis around ABO-I LDLT based on our recent experiences.