Misao Fujita

The first donor death after living-related liver transplantation in Japan.

On May 4, 2003, the first donor death after living-related liver transplantation (LRLT) occurred in Kyoto, Japan. The donor who died was a mother in her late forties who in August 2002 donated the right lobe of her liver to her adolescent daughter with liver cirrhosis caused by congenital biliary atresia. The mother’s liver function had deteriorated progressively after the donation. In January 2003, the mother finally fell into liver failure after an unsuccessful domino liver transplant from a donor with a metabolic disease. She died 4 months later without regaining consciousness. The daughter, who has recovered well, had initially received a liver from her father in 1994. Because of graft rejection, however, the daughter’s condition eventually deteriorated and she became critically ill before her second LRLT. The only potential living donor was her mother, who unfortunately had mild hypertension (systolic blood pressure, 150–160 mm Hg) and a slight fatty liver diagnosed by preoperative computed tomographic (CT) scan and echogram. After intense discussion, the transplant team reached the decision to undertake emergent LRLT surgery. When the donor later developed liver failure and died, the university hospital opened the case to the media and invited external inspection by the Japanese Liver Transplant Society. Histologic examination of the donor liver revealed that she had nonalcoholic steatohepatitis (NASH), a rare disease with a poor prognosis that is capable of progressing to liver cirrhosis or cancer (1). The transplant team initially planned to perform a right lobectomy without the middle hepatic vein, leaving an estimated residual liver volume by CT volumetry of 37%. During the operation, however, the team judged it better to perform a right lobectomy with the middle hepatic vein. The donor’s residual liver volume by CT volumetry was 28%, lower than the suggested safe range of 30%. LRLT has the potential to reduce the shortage of organs for transplantation worldwide (2). Although the pros and cons of living donation have been widely discussed (3), the ultimate priority is undoubtedly the safety of the donor. This is the first donor death that has occurred in some 2,300 LRLT undertaken in Japan. At Kyoto University, where approximately 900 cases have been undertaken, an institutional ethics committee evaluates each case and ensures adequate informed consent (4). In spite of these precautions and a procession of successful cases, the Japanese medical community has now experienced the ultimate tragedy inherent in living-related organ transplantation—the loss of a donor’s life. The Japanese transplant professionals now intend to (1) include testing for NASH (by biopsy) in the criteria for selecting donors at potential risk; (2) establish safer standards for preoperative CT volumetric analysis; (3) increase the required education team for selecting donors; and (4) amend the process of informed consent by including disclosure of unpredictable risk of rare complications including NASH. We hope that Japan’s experience of a death after LRLT and the procedural modifications learned from this misfortune will help contribute to the future sound development of LRLT worldwide.

The current status of clinics providing private practice cell therapy in Japan

AIM To clarify the current state of clinics in Japan that offer unproven cell therapies. METHODS Google searches were performed to collect and analyze what kind of clinics provide what kind of cell therapies. RESULTS A total of 74 clinics and 247 cases of cell therapies were identified. Various cell therapies, including allograft, were provided not only to seriously ill patients but also to patients with other therapeutic options and healthy individuals. DISCUSSION Although the practices revealed by our study seem to deviate from international standard, some of these can be construed as legal under the Japanese new act established in 2014. CONCLUSION Considering many patients travel to foreign countries to seek therapy, more research from non-English-speaking countries is needed.

Living related liver transplantation: a Japanese experience and development of a checklist for donors' informed consent

In the February 2002 issue of Gut , Broelsch et al argued for a controversial therapy of living related liver transplantation ( Gut 2002; 50 :143). The Japanese experience is somewhat different from those of other countries, as indicated in the article. Japan has long been the subject of sociocultural studies because of its delay in using the organs of brain dead persons for transplantation purposes. Since the Organ Transplant Law was enacted in 1997,1 only 16 liver transplant operations using brain dead donors have taken place. In contrast, more than 700 cases of liver transplants (with both children and adults as …

The decision-making process for the fate of frozen embryos by Japanese infertile women: a qualitative study

BackgroundPrevious studies have found that the decision-making process for stored unused frozen embryos involves much emotional burden influenced by socio-cultural factors. This study aims to ascertain how Japanese patients make a decision on the fate of their frozen embryos: whether to continue storage discard or donate to research.MethodsTen Japanese women who continued storage, 5 who discarded and 16 who donated to research were recruited from our infertility clinic. Tape-recorded interviews were transcribed and analyzed for emergent themes.ResultsA model of patients’ decision-making processes for the fate of frozen embryos was developed, with a common emergent theme, “coming to terms with infertility” resulting in either acceptance or postponing acceptance of their infertility. The model consisted of 5 steps: 1) the embryo-transfer moratorium was sustained, 2) the “Mottainai”- embryo and having another child were considered; 3) cost reasonability was taken into account; 4) partner’s opinion was confirmed to finally decide whether to continue or discontinue storage. Those discontinuing, then contemplated 5): the effect of donation. Great emotional conflict was expressed in the theme, steps 2, 4, and 5.ConclusionsPatients’ 5 step decision-making process for the fate of frozen embryos was profoundly affected by various Japanese cultural values and moral standards. At the end of their decision, patients used culturally inherent values and standards to come to terms with their infertility. While there is much philosophical discussion on the moral status of the embryo worldwide, this study, with actual views of patients who own them, will make a significant contribution to empirical ethics from the practical viewpoint.

Recent Court Ruling in Japan Exemplifies Another Layer of Regulation for Regenerative Therapy

The Japanese government recently put in place a system of standards, under the Act on the Safety of Regenerative Medicine (ASRM) (Konomi et al., 2015), for reviewing and approving regenerative medicine (RM) therapies. To obtain conditional approval, the protocols must fulfill a set of legal standards that varies in accordance with the risk level of the cells to be provided (see Figure S1). While this act provides a new regulatory framework for approving RM, providers of unapproved RM therapies have not been legally punished under the new law as of yet.

Public attitudes in Japan towards human–animal chimeric embryo research using human induced pluripotent stem cells

AIM To understand the steps and objectives for which Japanese people are willing to accept human-animal chimeric embryo research using human induced pluripotent stem cells. METHODS An internet-based survey was conducted for the general public and researchers in Japan in 2016. RESULTS Over 60% of the public and 83.8% of researchers supported the creation of human-swine chimeras and 81.0% of the public and 92.4% of researchers supported the creation of human-swine chimeric embryos. DISCUSSION When presented with a graded view of human-swine chimeric embryo research with concomitant, specific objectives, a large majority of the general public as well as researchers are willing to accept this research with the aims of disease study, novel drug and treatment development, and transplantation.

Evaluating the Quality of Website Information of Private-Practice Clinics Offering Cell Therapies in Japan.

Background Although the safety and effectiveness of stem cell therapies are yet to be proven, recent studies show that such therapies are being advertised with some questionable marketing techniques to effect positive portrayal of the therapies on the webpages of private-practice clinics to sell their therapies worldwide. In such context, those clinics communicate directly with consumers (patients and their family members) via the clinics’ websites. Meanwhile, the Health Science Council at the Ministry of Health, Labour, and Welfare (MHLW) in Japan has pointed out noncompliance of some local clinics with the provisions concerning medical advertising in the Medical Care Act in the past. However, locally little is known about the current status of those clinics including the quality of their webpage information disseminated. Objective To evaluate the quality of website information of private-practice clinics offering cell therapies in Japan. Methods Twenty-four websites with 77 treatments from the Google search were identified for evaluation. The following three exploratory analyses were performed: first in order to ascertain web-based portrayal of private-practice clinics offering cell therapies, a descriptive analysis was conducted using a coding frame; second we evaluated the quality of the target website information from the viewpoint of the level of consideration taken for patients and their family members, using 10 quality criteria (“the Minimum Standard”) from the e-Health Code of Ethics 2.0; third we counted and coded expressions that matched set categories for “name-dropping” and “personalized medicine” in the information posted on these websites. Results Analysis on the treatments (N=77) revealed 126 indications (multiple response): the top three indications were “cancer,” “skin-rejuvenation/antiaging/anti–skin aging,” and “breast augmentation/buttock augmentation.” As for the portrayal of treatment risks and benefits, 78% (60/77) of treatments were mentioned with “benefits,” whereas 77% (59/77) of treatments were mentioned with “risks.” As for the source(s) cited for the discussions of treatment risks and benefits, no treatment quoted an expert’s opinion for the risks, whereas 7% (6/77) treatments quoted external sources for the benefits. As for the results with e-Health Code of Ethics 2.0, not a single clinic fulfilled all the 10 criteria; 63% (15/24) of the clinics was found exercising “name-dropping,” and 21% (5/24) of the clinics mentioned expressions related to “personalized medicine” on their websites. Conclusions Our website content analyses confirmed the following: (1) the clinics mentioned the risks or benefits of the treatments with hardly any scientific citations, (2) the way the website information was disseminated was inappropriate for patients and their families, and (3) many websites seemed to be using marketing techniques in order to draw patients’ interests or attentions. It is important that more similar studies are undertaken globally to enable an orchestrated regulatory approach toward private-practice clinics.

Handling incidental findings in neuroimaging research in Japan: current state of research facilities and attitudes of investigators and the general population.

BackgroundTo establish appropriate measures that deal with incidental findings (IFs), the neuroscience community needs to address various ethical issues. The current state of research facilities regarding IFs and investigator attitudes as well as potentially eligible research participants must be assessed prior to future discussions and before the development of policies and guidelines. To this end, we conducted two questionnaire surveys to clarify i) how IFs are addressed at neuroimaging research facilities in Japan and ii) the views of investigators and potential research participants regarding the handling of IFs.MethodsThirty-one principal investigators (PIs) involved in the Strategic Research Program for Brain Sciences (SRPBS), a government-funded project, were asked to fill out a questionnaire regarding ways IFs were handled at the facility. A total of 110 investigators engaged in SRPBS tasks, including 31 PIs who participated in the research facility survey and researchers conducting studies under the management of the PIs, and 500 individuals from the general public (i.e., general population) were asked to select the most appropriate way to deal with IFs in two scenarios, namely the medical school and humanities and social sciences department scenarios.ResultsMore than 40% of PIs responded that they did not know or were unsure of what type of approach was employed to handle IFs at their research facilities. Nevertheless, they were willing to improve the current status if sufficient resources were provided. With regard to specialist involvement, 37.7% of investigators responded that it was appropriate to have a specialist check all images in the medical school scenario, whereas 13.3% responded that such involvement was appropriate in the humanities and social sciences department scenario. In contrast, 76.1% and 61.0% of the general population indicated that specialist involvement was appropriate in the medical school and humanities and social sciences department scenarios, respectively. These results show that expectations of the general population exceed those of investigators regarding measures to address IFs. Both investigators and the general population demanded more responsibility from PIs at medical institutions, compared to PIs at non-medical institutions.ConclusionsBased on our preliminary results, we recommended that a licensed physician perform a screening test to appropriately examine clear abnormalities. These recommendations were implemented by the SRPBS as guidelines for handling IFs in national research projects in Japan.

Discovery and informing research participants of incidental findings detected in brain magnetic resonance imaging studies: Review and multi-institutional study

Brain imaging studies using magnetic resonance imaging (MRI) sometimes reveal incidental findings (IFs) that might be relevant to some of the health issues in research participants. Although professional communities have discussed how to manage these IFs, there is no global consensus on the concrete handling procedures including how to inform participants of IFs.

Throwing the baby out with the bathwater: a critique of Sparrow's inclusive definition of the term ‘in vitro eugenics’

Sparrow highlights three potential applications of in vitro eugenics, that is, (a) research into the heredity of genetic disorders, (b) production of cell lines with specific genotypes, and (c) breeding better babies, and points to the need for researchers to discuss in advance the potential ethical problems that may emerge if the realization of this technology occurs in the near future. In this commentary, we pose a question for the sake of discussion. Is it, in fact, appropriate to label all three applications raised by Sparrow as eugenics? By doing so, an unnecessary level of concern might be borne among the public, and as a result, the sound development of this specialized technology would be affected. If the label of eugenics is to be applied to all three of these applications, then Sparrow must justify how he perceives (a) and (b) as not inherently different from (c).