A hepatologist have three major roles in a liver transplantation in Japan: pretransplant evaluation for liver transplant recipients and living donors; management of recurrent liver diseases after transplantation; and research based on new aspects of liver transplantation. All roles are performed in collaboration with medical staff personnel in many clinical departments. This collaboration results in the improvement of prognosis after a liver transplantation and the development of hepatology.

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Pancreas transplantations are carried out on patients whose insulin secretion is completely depleted. As a long-standing type 1 diabetes patient and also as a diabetologist, I find it not so difficult to control blood glucose in most patients who apply simultaneous pancreas kidney transplant. As a transplant physician, I focus on topics about blood glucose control before and after pancreas transplant, management of the medical team during the perioperative period, insulin independence, and pancreas graft loss.

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Heart transplantation (HTx) was originally developed by cardiac surgeons, but it has been popularized by many transplant cardiologists world wide since the 1980s. In Japan, however, only a few cardiologists have been involved. But cardiologists and physicians in other fields can now be involved in many ways both before and after HTx. Before HTx, intensive care, including essential medication management, cardiac resynchronization therapy, adaptive servoventilation, and ventricular assist device implantation should be considered for HTx candidates. During the waiting period of approximately 1000 days before HTx, patients should be maintained in stable condition. In the acute phase after HTx, many approaches are needed to diagnose and treat rejection and infection and to manage the adverse effects of immunosuppression. During the chronic stage after HTx, major complications such as cardiac allograft vasculopathy, malignancy, and renal dysfunction should be detected and treated as early as possible, sometimes with modifications in immunosuppressant regimens. The relationship between patients and medical providers should consist of mutual trust and dependence. Narrative-based and evidence-based medicines are both very useful, especially in the chronic stage after HTx, to prevent nonadherence. Various specialists should be involved in the use of these medicines.

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Nephrologists are expected to play multiple roles in the field of kidney transplantations. They first need to advise transplant recipients that a transplantation is one of the renal replacement therapies. They will then evaluate and adjust the condition of recipients from the preoperative to the perioperative periods and explain how to care for lifetime chronic kidney disease management. Furthermore, nephrologists are also required to evaluate the psychological conditions, of donors and to perform treatment intervention for keeping eGFR after a nephrectomy. These multidisciplinary responsibilities are all considered very important.

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Patients undergoing renal transplantation (RTx) have high risks for coronary artery diseases and congestive heart failure (CHF). Therefore a preoperative survey includes myocardial perfusion images and echocardiography. If a patient has more than two revised cardiac risk Index, a β blocker should be considered by careful titration to maintain the mean heart rate ≦70 bpm. Percutaneous coronary intervention (PCI) should be avoided when the volume of ischemic myocardium is less than 20%. Left ventricular ejection fraction of less than 45% indicates two fold high incidences of cardiovascular events following RTx. Patients undergoing RTx tend to have left ventricular diastolic dysfunction, which is prone to result in CHF by volume overload or high blood pressure during the perioperative period. Tissue Doppler derived E/e' or e' should be assessed. Following PCI, aspirin should not be discontinued among patients with high risk for stent thrombosis. Discontinuation of dual anti-platelet therapy should be done in a hospital without substitution of heparin.

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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 the deceased donors for organ transplantation were almost the same in 2010, 2011 and 2012 and were decreased in 2013 and 2014. The percentage of the brain-dead donors slightly increased, but the total numbers of cardiac-arrested donors decreased intensely. Unexpectedly, in 2014, the total number of the deceased donors decreased to 77. The numbers of brain-dead and cardiac-arrested donors were 50 and 27. The organ transplantations from the deceased donors are realized with the efforts of the procurement teams. This is a report on organ procurement from the deceased donors for organ transplantations in Japan in 2014.

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A number of 1,598 kidney transplants including 1,471 from living donors, 42 from non-heart-beating donors and 85 from heart-beating donors were performed in 2014 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 the histocompatibilities are described. In addition, immunosuppressants used initially and other treatments are analyzed.
We also reported the results of follow-up survey for living donors.

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As of December 31, 2014, a total of 7,937 liver transplants have been performed in 67 institutions in Japan. This total included 7,673 living-donor transplants and 264 cadaveric-donor transplants (261 from heart-beating donor and 3 from non-heart-beating donor). The annual total of liver transplants in 2014 increased to 463, from 408, in 2013. The number of liver transplants from living-donor increased to 418, from 369, whereas the number of liver transplants from heart-beating cadaveric donor did not change significantly. The most frequent indication was cholestatic disease, followed by neoplastic disease. As for the graft liver in living-donor cases, right-lobe graft was the most popular (35%). Patient survival following transplantation from heart-beating donor (1 year, 87.1%; 3 year, 83.9%; 5 year, 83.1%; 10 year, 77.4%; 15 year, 77.4%) was similar to those from living-donors (1 year, 84.1%; 3 year, 79.9%; 5 year, 77.4%; 10 year, 72.2%; 15 year, 68.3%; 20 year, 66.6%). Graft survival was very much the same as patient survival. As for ABO-incompatible transplantation, new strategies including portal vein infusion and rituximab prophylaxis have been improving the prognosis in adults as well as in children older than 3 years.

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Since the Organ Transplantation Law was passed in October 1997, a total of 222 heart transplantations (HTx) have been performed in Japan as of December, 2014. Of those, 152 HTx were performed after activation of a modified transplant law, and 37 were performed in 2014. Most recipients had dilated cardiomyopathy; and the waiting condition of all patients, except for one pediatric patient, was status 1 at HTx. The mean waiting time as status 1 in 2014 was 879 days. Two hundred and three patients (91%) were bridge-to-transplant (BTT) cases by means of several types of left ventricular assist devices (LVAD). In 2014, BTT cases totaled 36 of 37 patients, and 81% of them were supported by several types of non-pulsatile implantable LVADs. Mean support duration was 879 days. The majority 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. Two patients have been doing well > 15 years after HTx, and the 10 year survival rate was 89.3 %, which is superior to that of the international registry. In 2014, one pediatric HTx was performed as a BTT.
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.

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【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 11th official registry report of Japanese lung transplantation.
【Design and Methods】The data of cadaveric lung transplantation and living-donor lobar lung transplantation performed by the end of 2014 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 238 cadaveric lung transplantation (127 single, 111 bilateral), 165 living-donor lobar lung transplantation and 2 heart-lung transplantation procedures were performed by the end of 2014. Five-year and 10-year survival rates of cadaveric lung transplantations were 72.1% and 59.2 %, which were superior to those in the International Registry (52.8% and 31.1%). Five-year and 10-year survival rates of living-donor lobar transplantations were similar to those of cadaveric lung transplantation with 71.9% and 65.1%. The recipients of 2 heart-lung transplantations are alive. The functional status of more than 80% of recipients was restored to Hugh-Jones I or II after transplantations. Infection has been the leading cause of death after lung transplantation. Primary graft dysfunction accounts for about 25% of the causes of death after cadaveric and living-donor lung transplantations.
【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. The modified Japanese transplantation law has been enforced since July, 2010, and an increase in the number of cadaveric organ transplantations has been achieved thereafter. The Japanese Society of Lung and Heart-Lung Transplantation will continue to present annual reports of Japanese lung transplantations.

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Two hundred and thirty seven cases of pancreas transplantation from deceased, non-heart beating and living-related donors have been performed in 17 institutions in Japan until the end of 2014 since April, 2000. The following donor- and recipient-related factors were analyzed; i.e., 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.
In spite of donor poor conditions which were mostly marginal in Japan, the outcome of pancreas transplants was considered to be comparable to that of the US and Europe.

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Islet transplantation can relieve glucose instability and problems with hypoglycemia while the graft is functioning. Islet transplants, though significantly improving, are still mostly done on an experimental basis. In Japan, we started the phase II clinical trial with type 1 diabetes patients for islet transplantation using both brain-dead donors and DCD to evaluate ATG induction and TNF inhibition protocol. Primary endpoints are the proportion of subjects with HbA1c＜7.4% and who are free of severe hypoglycemic events one years after the first islet cell infusion. This trial would play an important role in establishing islet transplantation in Japan.

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Twenty-four intestinal transplants were performed since 1996 in 5 institutions. There were 13 deceased donor and 13 living related donor transplants. Primary causes of intestinal transplants were short gut syndrome (n=9), intestinal mobility function disorder (n=13), others (n=1) and re-transplantation (n=3) ．1 year patient survival was 86%, and 10-year patient survival was 58%. They were excellent results for a standard therapeutic option for intestinal failure if patients fail to maintain total parental nutrition.

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Hematopoietic stem cell transplantation (HSCT) offers potentially curative treatment for a wide range of otherwise fatal hematologic disorders. The number of HSCTs has continued to increase over the past 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 patients (aged over 50), and an increase in the variety of donor/stem cell sources, such as cord blood from unrelated donors have led to this constant increase of HSCTs in Japan. The transplant survival outcomes also continue to improve, and the assets for improvement include better supportive care, innovative transplant approaches, and establishment of a transplant outcome registry.

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【Objective】The aim of this study was to reveal relevant factors of parents' perceived burden of nurturing in pediatric organ transplantation (liver, kidney, or heart) in Japan.
【Design ' Methods】Cross-sectional surveys of self-report anonymous questionnaires and medical records were completed from September 2013 to March 2014. Perceived burden of nurturing was measured by existing transplant-nonspecific and newly developed transplant-specific scale.
【Results】We received 87 participation (participation rate: 83.7%). “Participation in support group" (standardized partial regression coefficients: β＝－0.19); “lower perceived stigma for organ transplantation from others" (β=0.37); “higher recipient age at survey" (β＝－0.42); “shorter commuting time between home and primary follow-up hospital" (β=0.19); “higher family functioning" (β＝－0.22); and “higher social support" (β＝－0.22) were related to lower perceived burden of nurturing (adjusted coefficients of determination=0.52).
【Conclusion】Based on these results, the facilitation of support from family, society, and support group and establishment of emergency procedures including local hospitals are important for decreasing parents' perceived burden of nurturing.

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【Objective】 We assessed the pancreas marginal donor criteria of the University of Minnesota (UM), the University of Pittsburgh (UP), the EXPAND study, and the Japanese Society for Pancreas and Islet Transplantation Association (JPITA) in our sixteen donor series.
【Design】Retrospective case series
【Methods】Marginal donor was defined as follows: (1) ＞45years old, (2) hemodynamically unstable at harvest using high-dose dopamine or more than 2 vasopressors in UP criteria; (1) ＞45years old, (2) cerebro-cardiovascular disease death in UM criteria; (1) 50 to 60 years old, (2) body mass index (BMI) of 30 to 34 kg/m² in EXPAND criteria; (1) ＞60 years old, (2) BMI ＞30 kg/m² in JPITA criteria.
【Results】 The marginal donor was defined in fifteen cases (94%) for UP and/or UM criteria; in eight cases (50%) for EXPAND criteria; and in two cases (13%) for JPITA criteria. Primary nonfunction and pancreas graft removal was not found in our series for thrombosis, pancreatitis and acute rejection. Actual pancreas graft survival was 86% with a mean follow-up of 37months.
【Conclusion】Pancreas graft survival from marginal donor in our series was acceptable. Utilization of pancreata from marginal donors may expand the availability of pancreas grafts for transplantation.

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【Objective】The role (s) of Collagenase G (ColG) and Collagenase H (ColH) during pancreatic islet isolation remain controversial, possibly due to the enzyme blends used in the previous studies. We herein examined the role of ColG and ColH using highly pure enzyme blends of recombinant collagenase of each subtype.
【Design】Animal experimental study
【Methods】Rat pancreases were digested using thermolysin, together with ColG, ColH, or ColG/ColH (n=9, respectively). No tryptic-like activity was detected in any components of the enzyme blends. The efficiency of the collagenase subtypes was evaluated by islet yield and function. An immunohistochemical analysis, in vitro collagen digestion assay, and mass spectrometry were also performed to examine the target matrix components of the crucial collagenase subtype.
【Results】The islet yield in the ColG/ColH group was the highest （4,101±460 islet equivalents）. A substantial number of functional islets （2,811±581 islet equivalents） were obtained in the ColH group, whereas no islets were retrieved in the ColG group. Mass spectrometry demonstrated that ColH reacts with collagen I and III. In the immunohistochemical analysis, both collagen I and III were located in exocrine tissues, although collagen III expression was more pronounced. The collagen digestion assay showed that collagen III was more effectively digested by ColH than by ColG.
【Conclusion】The present study reveals that ColH is crucial, while ColG plays only a supporting role, in rat islet isolation. In addition, collagen III appears to be one of the key targets of ColH.

This article is a secondary publication in Japanese of "Collagenase H is crucial for isolation of rat pancreatic islets" published by Fujio A, Murayama K, Yamagata Y, et al. Cell Transplant 2014; 23: 1187-1198.

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We report a case of right-lobe living-donor liver transplantation using the cystic duct for biliary tract reconstruction. The patient was a 49-year-old woman who underwent the transplantation for fulminant hepatitis. The donor was her husband, and his preoperative DIC-CT examination showed that the right posterior segmental bile duct spontaneously merged into the common bile duct and was widely separated from the right anterior segmental bile duct. During the operation, it was impossible to transform the anterior duct and posterior duct into a single orifice because the orifices of the ducts were widely separated. Therefore the posterior duct and the anterior duct were separately anastomosed with the cystic duct and the common hepatic duct. Cholangiography and biliary scintigraphy three months after the transplantation and MRCP three years later showed no leakage or stricture at the anastomotic sites. The case suggested the feasibility of usage of cystic duct for biliary tract reconstruction during living-donor liver transplantation.

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