This report presents the Japanese status for organ procurement from deceased donors for organ transplantation in 2017. The year 2017 was the twentieth anniversary of the enforcement of the Act on Organ Transplantation. After the enforcement of the amended Act on Organ Transplantation in July 2010, the number of brain-dead donors vastly increased. But the total numbers of deceased donors for organ transplantation, which were almost the same in 2010, 2011, and 2012, decreased in 2013 and 2014 and slightly increased in 2015 and 2016. In 2017, the total number of deceased donors increased by over 110. The organ procurement for transplantation from deceased donors is supported by the efforts of procurement teams.
A total of 1,742 kidney transplants including 1,544 from living donors, 65 from non-heart-beating donors and 133 from heart-beating donors were performed in 2017 in Japan.
The data obtained from the Japanese Renal Transplant Registry are shown and analyzed in this annual report. The characteristics of recipients and donors such as relationships, original diseases, duration of dialysis therapy, blood transfusion, the status of viral antigens and antibodies, pretransplant complications, the causes of death of deceased donors, ischemic time and histocompatibilities are described. In addition, immunosuppressants used initially and other treatments are analyzed.
We also report the results of a follow-up survey for recipients and living donors.
As of December 31, 2017, a total of 9,242 liver transplants have been performed in 67 institutions in Japan. There were 447 deceased-donor transplants (444 from heart-beating donors and 3 from non-heart-beating donors) and 8,795 living-donor transplants. The annual total of liver transplants in 2017 was 416 (69 deceased-donor transplants and 347 living-donor transplants). The most frequent indication was cholestatic disease, followed by neoplastic disease and hepatocellular disease. As for hepatocellular disease in 2017, cirrhosis due to hepatitis C and B decreased (13 and 8, respectively), whereas alcoholic cirrhosis markedly increased (32). Patient survival following transplantation from heart-beating donors (444 transplants: 1-year 89.1%, 3-year 85.2%, 5-year 82.9%, 10-year 75.4%, 15-year 70.7%) was similar to that from living-donors (8,794 transplants: 1-year 85.0%, 3-year 80.9%, 5-year 78.5%, 10-year 73.2%, 15-year 68.5%, 20-year 65.7%, 25-year 64.6%). Graft survival was very much the same as patient survival (heart-beating donors: 1-year 88.4%, 3-year 84.5%, 5-year 82.2%, 10-year 74.7%, 15-year 70.1%，living-donors: 1-year 84.3%, 3-year 79.9%, 5-year 77.3%, 10-year 71.4%, 15-year 66.3%, 20-year 63.3%, 25-year 61.9%). Survival data are reported according to age and sex of recipient, indication, age and sex of donor, ABO-compatibility, and other factors.
Since the Organ Transplantation Law was passed in October 1997, a total of 373 heart transplantations (HTx) have been performed in Japan as of December, 2017. Of those, 304 HTx were performed after activation of a revised Transplant Act, and 56 were performed in 2017. Most recipients had dilated cardiomyopathy; and the waiting condition of all adult patients was status 1 at HTx. The mean waiting time as status 1 continuously increased to 1174 days in 2017 from 873 days in 2014. After approval of the use of an implantable continuous flow ventricular assist device (cf-LVAD) for bridge-to-transplant (BTT) in 2011, BTT, especially using cf-LVAD increased. In 2017, all patients were BTT cases, and 51 (91%) of them were supported by several types of cf-LVADs. Mean support duration also continuously increased to 1211 days in 2017 from 876 days in 2014. Twenthy-six children underwent HTx and 21 (81%) of them were BTT cases (8 in Nipro VAD, 5 in EXCOR VAD, 5 in Jarvik and 3 in other cf-VAD). Most of patients received a modified bicaval method of operation with Celsior for cardiac preservation, and all recipients were administered triple therapy with calcineurin inhibitor (cyclosporine or tacrolimus), mycophenolate mofetil, and steroid as an initial immunosuppressive regimen. Patient survival at 10 and 15 years was 88.2% and 83.4%, respectively, which is superior to that of the international registry. This surveillance documented that the results of HTx in Japan were excellent despite a severe shortage of donors and long waiting times with LVAD as BTT.
【Objective】 To scrutinize the status of lung transplantation in Japan, the Japanese Society of Lung and Heart-Lung Transplantation started to collect and present registry data from 2005. This is the 14th official registry report of Japanese lung transplantation.
【Design and Methods】 The data on cadaveric lung transplantation and living-donor lobar lung transplantation performed by the end of 2017 were registered in the database and analyzed with respect to the number of transplants, recipient survival rates, recipient functional and working statuses, and causes of death after transplantations. Survival rates were calculated by the Kaplan-Meier method.
【Results】 A total of 388 cadaveric lung transplantation (201 single, 187 bilateral), 208 living-donor lobar lung transplantation and 3 heart-lung transplantation procedures were performed by the end of 2017. Five-year and 10-year survival rates of cadaveric lung transplantations were 71.7% and 55.7%, which were superior to those in the International Registry. Five-year and 10-year survival rates of living-donor lobar transplantations were similar to those of cadaveric lung transplantations with 73.4% and 64.1%. The recipients of the 3 heart-lung transplantations are alive. The functional status of more than 80% of recipients was restored to a mMRC scale of grade 0 or 1 after transplantation. Infection has been the leading cause of death after lung transplantation. Chronic lung allograft dysfunction and primary graft dysfunction accounts for about 17% of the causes of death after cadaveric and living-donor lung transplantation.
【Conclusion】 The outcomes of Japanese lung transplantation are so far satisfactory. Efforts must be made, however, to overcome early deaths resulting from primary graft dysfunctions and chronic lung allograft dysfunction. The modified Japanese transplantation law has been enforced since July 2010, and an increase in the number of cadaveric organ transplantations was achieved thereafter. The Japanese Society of Lung and Heart-Lung Transplantation will continue to present annual reports of Japanese lung transplantations.
A total of 354 cases of pancreas transplantation from deceased, non-heart beating and living-related donors were performed in 18 institutions in Japan between April, 2000 and the end of 2017. The following donor- and recipient-related factors were analyzed: age and gender of donor and recipient, cause of death, histories of diabetes and dialysis, waiting period, total cold ischemic time, operative procedure, immunosuppression and survival rates of patient and graft. We showed the current status of pancreas transplantation in Japan. Although the donor conditions have improved every year, they are still mostly marginal. However, the outcome of pancreas transplants was considered to be comparable to that of the US and Europe. The most critical problem was that the pancreas graft survivals of PAK and PTA were significantly poorer than that of SPK. We should propose our original safety criteria for pancreas transplants to achieve long-term graft survival.
Islet transplantation is promising to be capable of relieving glucose instability and improving QOL of type 1 diabetic patients whose severe hypoglycemic unawareness cannot be controlled. In Japan, a phase II clinical trial of islet transplantation for type 1 diabetes patients has been started using ATG induction and a TNF-α inhibition protocol. Primary endpoints for this trial are the proportion of subjects with HbA1c<7.4% who are free of severe hypoglycemic events one year after the first islet cell infusion. This trial will play an important role in establishing islet transplantation in Japan.
Twenty-seven intestinal transplants were performed since 1996 in 5 institutions. There were 14 deceased donor and 13 living related donor transplants. Primary causes of intestinal transplants were short gut syndrome (n=9), intestinal mobility function disorder (n=14), others (n=1) and retransplantation (n=3). One-year patient survival was 88%, and 10-year patient survival was 51%. These were excellent results for a standard therapeutic option for intestinal failure if patients fail to maintain total parental nutrition.
Hematopoietic stem cell transplantation (HSCT) offers potentially curative treatment for a wide range of otherwise fatal hematologic disorders, and the number of HSCTs has continued to increase over the last 20 years, and more than 5,000 allogeneic and autologous HSCTs have been performed annually in recent years. A constant increase of allogeneic HSCTs for older (aged over 50) patients, and an increase in the variety of donor/stem cell source such as cord blood from unrelated donors have led to this constant increase of HSCTs in Japan. The transplant survival outcome also continues to improve and the assets for the improvement include better supportive care, innovative transplant approaches, and the considerable contribution of a well-established transplant outcome registry to a variety of clinical studies.
Organ transplantation has been established as a definitive therapy for patients with terminal organ failure. However, the chronic shortage of organ donors remains a major problem. Xenotransplantation offers the possibility of overcoming this problem. There has recently been considerable progress in the results of organ xenotransplantation in pig-to-nonhuman primate models, largely associated with the availability of various genetically-engineered pigs as sources of organs, in combination with novel immunosuppressive (based on co-stimulation blockade) and anti-inflammatory regimens. In the preclinical heterotopic (non-life-supporting) heart transplant model, pig graft survival has increased to >2 years. As for life-supporting pig kidney transplantation, recipient (nonhuman primate) survival has been extended to >1 year. Such progress has sufficiently encouraged us to begin realistic consideration of the clinical application of xenotransplantation. The process for clinical trials is already underway.
【Objective】 Pediatric liver transplantations are almost always performed at the request of the parents. Few studies have examined the need to explain the procedure to the children. The aim of this study was to clarify the timing and content of explanations for the recipients of a pediatric liver transplantation.
【Methods】 During the study period, 262 liver transplant recipients and their parents at the National Center for Child Health and Development, excluding patients older than 18 years or living abroad, were asked to respond to an onymous, self-administered questionnaire including the timing and the content of explanations about the transplant operation.
【Results】 There were 173 respondents of the 262 parents (response rate: 66.0%). Of these, 56% responded that they had explained the need for the operation to their child. All the parents of elementary school-aged and junior high school-aged patients reported explaining the reasons for the operation to their child. Some 38% of the parents did not explain the reason for the operation, and 42% of the parents responded that this was necessary only if their child “starts asking about (the operation) or is old enough to understand these matters.” For all children older than junior high school-age who received an explanation (and gave informed consent), the wishes or opinions of the patient influenced the decision to perform the transplantation.
【Conclusion】 To facilitate pediatric liver transplant recipients’ postoperative management of their own health, the medical staff and the parents need to better how better to provide patients with appropriate explanations about their disease and operation as they mature. To achieve this aim, in addition to the patients’ informed assent or consent with the procedure, criteria based on an objective developmental assessment are needed to counsel pediatric transplant patients in a timely manner.
In October 2016, a donor action program (DAP) was set up in our hospital for the establishment of a smooth regional organ donation system respecting the patient’s intent to the maximum. DAP consisted of 4 committees: brain death judgement and management, potential donor evaluation, and supervisory. Five multi-disciplinary in-house coordinators were assigned in DAP to share their roles utilizing their specialty. Fourteen cases of potential donors were detected and a proposal for organ donation was made in 12 cases during the year after DAP started. As a result, three cases of eye donation and one case of brain-dead organ donation were carried out.
【Purpose】 We reviewed our experience of liver transplantation in the National Center for Child Health and Development and report the results herein.
【Subjects and methods】 We have handled 500 cases of liver transplantation from November 2005 through March 2018 in the National Center for Child Health and Development. Variables including indication of liver transplantation and immunological outcome were reviewed.
【Results】 There were 469 living donor, 27 deceased and 4 domino liver transplantations in the study period. The indication for liver transplantation was cholestatic liver disease in 48.0%, followed by metabolic liver disease in 22.0% and acute liver failure in 12.6%. The mean age of recipients was 4.0±5.5 years and body weight was 14.9±13.3 kg. Immunosuppression consisted of tacrolimus and low-dose steroids. The incidence of acute cellular rejection was 42.0%. The 10-year patient survival was 90.2%.
【Conclusion】 Satisfactory results can be achieved in the liver transplantation program in the National Center for Child Health and Development. Deceased donor liver transplantation, patients with acute liver failure and re-transplantation shows significantly lower patient survival. We conclude that liver transplantation is a safe and effective treatment modality together with proper indication and excellent management strategy. The significant factors affecting survival may be overcome by the technical and immunological refinements that have occurred in recent years.
【Introduction】 After organ transplantation, the incidence of malignancy is one of the most worrisome problems. Here we report a case of early peritoneal recurrence of gastric cancer after living donor liver transplantation (LDLT).
【Case】 The patient, who was a female in her 60s, underwent a distal gastrectomy with D2 lymphadenectomy and Roux-en-Y reconstruction for advanced gastric cancer and was administered adjuvant chemotherapy for 5 years after the operation. There was no recurrence confirmed in her in any exams for 10 years after the operation. Although she achieved SVR for HCV hepatitis through the anti-viral therapy, she was diagnosed as already suffering severe liver cirrhosis. Because she had acute on chronic liver failure with the resistance of conservative therapies, she underwent LDLT using a right lobe graft from her sister. Afferent loop syndrome occurred at 2 months after LDLT, due to the peritoneal recurrence of gastric cancer. Finally she died at 5 months after LDLT.
【Conclusion】 We experienced the early peritoneal recurrence of gastric cancer after LDLT. We have to carefully consider the indications for the LDLT candidates with pretransplantation cancer history individually, according to the histological type of cancer, the histological stage and malignancy-free delay periods.
Patients with chronic renal failure have potential risks due to atherosclerosis and occasionally develop surgical complications, such as arterial dissection in regions of vascular anastomoses. We present a case of iliac artery dissection following kidney transplantation.
The patient was a male in his seventies with end-stage kidney disease primarily due to glomerulonephritis who had not been on chronic hemodialysis therapy. He underwent a kidney transplantation from a healthy living donor in his sixties, and the graft artery was sutured to the recipient’s right external iliac artery in side-to-end fashion. The recipient was reported to be negative anti-donor HLA preformed antibodies and had no other immunological risks.
The serum creatinine levels started to increase on day 13 post transplant, whereas the graft had been functioning immediately after transplantation. The ultrasound doppler examination indicated impaired blood perfusion in the transplanted kidney. Further examinations by angiography and intravascular ultrasound (IVUS) distinctively displayed an intimal flap in the right external iliac artery.
The patient was diagnosed with arterial dissection causing insufficient blood inflow to the graft. An intra-arterial stent was soon placed in the dissected artery by the interventional radiology technique. After this procedure, the intra-graft blood flow recovered and the patient’s serum creatinine levels decreased within two weeks.
We report a case of acute kidney injury of transplant due to external iliac artery dissection successfully treated with intra-arterial stent placement. It should be noted that older patients with chronic renal failure have a risk of arterial dissection of anastomosis sites, and IVUS is one of the useful devices for an appropriate diagnosis potentially leading to prompt therapy.