Lymphangioleiomyomatosis (LAM) is a rare neoplastic disease characterized by the proliferation of abnormal smooth muscle-like cells (LAM cells) that lead to cystic destruction of the lungs, chylous effusions, and the formation of lymphangioleiomyomas. Although lung transplantation for LAM accounts for only 1% of all lung transplant procedures in the International Registry, it does account for 16% in the Japanese Registry, and LAM is one of the major indications in Japanese lung transplantation. Recurrence of LAM in the allograft is one of the disease-specific complications after lung transplantation. The rates of recurrence, however, have been reported to be <10%, and the recurrence rarely affects the recipient's prognosis. Recently, sirolimus, an mTOR inhibitor, emerged as a therapeutic drug for LAM and is also expected to be effective for the recurrence of LAM after lung transplantation.

Primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) are major indications for liver transplantation. Despite the advance of medical treatments for these diseases, not a few patients develop cirrhosis and finally require liver transplantation. With the accumulation of experiences of liver transplantations for PBC and PSC, the disease recurrence has become a matter of debate. Although recurrent PBC is usually slow growing and has minimal impact on a patient's prognosis, recurrent PSC significantly impairs patient and graft survival. Moreover, in Japan, where living-donor liver transplantation (LDLT) is a mainstay for liver transplantation, LDLT-specific factors related with the development and progression of the recurrent disease have been identified by the recent nationwide studies. In this review article, we discuss the recurrent PBC and PSC after liver transplantations, with special reference to LDLT.

Hepatitis C recurrence after orthotopic liver transplantation (OLT) has been accepted as a major problem after OLT. Recent progress in hepatitis C virus (HCV) treatment with the use of direct acting antivirals (DAA) has almost resolved this major issue, as 95-100% of non-OLT hepatitis C patients in Japan reach a sustained viral response (SVR). However, the SVR rate among post-OLT hepatitis C patients in the United States and Europe is reported to be 90% and 10% of these patients require an additional approach. As the pathogenesis of hepatitis C involves immunological responses, post OLT hepatitis C exhibits complex phenomena with immune regulating agents including prednisolone and calcineurin inhibitors and HLA-mismatch in the recipient immune system and the donor liver. The pathogenesis and the recent progress in post-OLT hepatitis C are described in this chapter.

Focal segmental glomerulosclerosis (FSGS) is a histological pattern of injury in the kidney that has multiple different etiology, including obesity, viral infection, drug, and genetic disease. Primary idiopathic FSGS, its etiology is still not well defined, and it commonly progresses to end stage renal disease (ESRD). When a transplantation is performed, primary idiopathic FSGS may recur in the renal allograft. The reported FSGS recurrence rate averages approximately 30%, and patients who develop recurrent disease in the first transplant are at very high risk （>80%） for recurrence in subsequent allografts. Five-year graft survival rate for recurrent FSGS is about 50% with persistent nephrotic syndrome. Major risk factors for recurrence of FSGS include childhood onset of initial disease, rapid progression of initial disease, and a history of recurrence in a prior allograft. The histologic subtype of FSGS does not appear to predict the risk of recurrence, and a family history generally predicts a low risk of recurrence. Patients who have recurrent primary FSGS typically present with the rapid onset of proteinuria, which is frequently in the nephrotic range. The diagnosis of FSGS is made by renal biopsy findings in the setting of significant proteinuria （>1 gram/day）. No immunosuppressive therapies have been conclusively shown to prevent FSGS in the transplanted kidney. Though no standard treatment for recurrent FSGS is verified yet, prolonged beneficial results have been reported with plasmapheresis and rituximab. Although definitive data are not available, early initiation of these therapies may be recommended after the onset of recurrent disease before development of irreversible histologic changes.

The recurrence rate of immunoglobulin A (IgA) nephropathy after kidney transplantation is 50%-60% or 13%-50%, based on histopathological or clinical findings, respectively, and graft loss from recurrence is 1.3%-16%. IgA nephropathy is treated as a combination of focal glomerular vasculitis and secondary focal segmental glomerulosclerosis (FSGS). In the early stage, IgA nephropathy has glomerular vasculitis accompanied by hematuria. As sclerosis gradually develops in the kidneys, secondary FSGS with increasing proteinuria becomes the primary concern in the advanced stage of IgA nephropathy. Glomerular hyperfiltration easily induces secondary FSGS in a transplanted kidney. However, angiotensin-converting enzyme inhibitors and angiotensin receptor blockers effectively suppress recurrent IgA nephropathy accompanied by proteinuria. As for IgA nephropathy in native kidneys, remission is possible when glomerular vasculitis is treated early with tonsillectomy plus pulse steroid therapy. This combination therapy is also effective for the remission of recurrent IgA nephropathy with clinical findings. Maintenance steroid therapy is associated with a reduced risk of kidney graft loss from recurrent IgA nephropathy. Furthermore, the incidence of recurrence of IgA nephropathy is decreasing because of new drugs (anti-thymocyte globulin and anti-CD25 antibody drug basiliximab) used in induction immunosuppressive therapies, presumably through the improvement of glomerular vasculitis. At present, 3 cases using rituximab have been reported. Because a wide range of immunosuppressive drugs are available for use in kidney transplantation, clinical studies using these new drugs are expected to establish treatment methods for IgA nephropathy, even in pretransplant patients.

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,were decreased in 2013 and 2014, and slightly increased in 2015. But the percentage of the brain-dead donors slightly decreased in 2015. In 2015, the total number of the deceased donors increased to 91. The numbers of brain-dead and cardiac-arrested donors were 58 and 33. 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 2015.

A number of 1,661 kidney transplants including 1,494 from living donors, 63 from non-heart-beating donors and 104 from heart-beating donors were performed in 2015 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 report the results of follow-up survey for recipient sand living donors.

As of December 31, 2015, a total of 8,387 liver transplants have been performed in 67 institutions in Japan. There were 8,066 living-donor transplants and 321 cadaveric-donor transplants (318 from heart-beating donor and 3 from non-heart-beating donor). The annual total of liver transplants in 2015 was 448. The number of liver transplants from living-donor decreased to 391, from 419, in 2014, whereas the number of liver transplants from deceased-donor exceeded 50 for the first time. 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, 86.7%; 3 year, 83.4%; 5 year, 81.1%; 10 year, 75.8%; 15 year, 75.8%) was similar to those from living-donor (1 year, 84.4%; 3 year, 80.3%; 5 year, 77.8%; 10 year, 72.5%; 15 year, 68.4%; 20 year, 66.1%; 25 year; 65.0%). Graft survival was very much the same as patient survival. Survival data were provided 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 266 heart transplantations (HTx) have been performed in Japan as of December 2014. Of that total, 196 HTx were performed after activation of a revised Transplant Act, and 44 were performed in 2015. Most recipients had dilated cardiomyopathy; and the waiting condition of all patients was status 1 at HTx. The mean waiting time as status 1 increased to 1059 days in 2015, from 873 days in 2014. After approval of the use of implantable continuous-flow left ventricular assist device (cf-LVAD) for bridge-to-transplant (BTT) since 2011, BTT, especially using cf-LVAD, increased. In 2015, BTT cases totaled 43 of 44 patients, and 91% of them were supported by several types of cf-LVADs. Mean support duration increased to 1049 days in 2015, from 876 days in 2014. Twelve children underwent HTx after LVAD implantation (8 in Nipro VAD, 2 in EXCOR VAD, and 2 in cf-VAD). Most 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 91.6% and 83.2%, 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 12th 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 2015 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 283 cadaveric lung transplantation (150 single, 133 bilateral), 181 living-donor lobar lung transplantation and 2 heart-lung transplantation procedures were performed by the end of 2015. Five-year and 10-year survival rates of cadaveric lung transplantations were 72.1% and 58.8%, which were superior to those in the International Registry (53.0% and 31.0%). Five-year and 10-year survival rates of living-donor lobar transplantations were similar to those of cadaveric lung transplantation with 71.7% and 65.9%. The recipients of 2 heart-lung transplantations are alive. The functional status of more than 75% of recipients was restored to a mMRC scale of grade 0 or 1 after transplantations. Infection has been the leading cause of death after lung transplantation. Primary graft dysfunction accounts for about 20% 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.

Two hundred and seventy three 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 2015 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.

Islet transplantation promises to be capable of relieving glucose instability and improving QOL of type 1 diabetic patients who suffer from uncontrolled severe hypoglycemic unawareness. In Japan, the phase II clinical trial of islet transplantation for type 1 diabetes patients has been started using ATG induction and TNF-α inhibition protocol. Primary endpointsfor this trial are the proportion of subjects with HbA1c<7.4% and who are free of severe hypoglycemic events one year after the first islet cell infusion. This trial would play an important role in establishing islet transplantation in Japan.

Twenty-six 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 87%, and 10-year patient survival was 61%. They 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 HSCT has continued to increase over the last 20 years, and more than 5,000 allogeneic and autologous HSCT are performed annually in recent years. A constant increase of allogeneic HSCT 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 HSCT in Japan. The transplant survival outcome also continues to improve and the assets for the improvement include the better supportive care, innovative transplant approaches and the establishment of transplant outcome registry.

【Objective】Because of revisions of the Japanese Organ Transplantation Act, brain-dead organ donations increased and the roles of in-hospital procurement coordinators (In-hp PTCs) became more important. The purpose of this study is to evaluate the effects and efficiencies of our education program for In-hp PTCs.
【Design】Intervention research
【Methods】We established special educational seminars for In-hp PTCs to provide an educational program for them to be held twice a year in Osaka during 2012 and 2013. Briefly, these seminars each consisted of 14 educational items (11 didactic lectures and 3 simulation group). In the first semester, two-hour lectures were provided every two weeks for 5 months. In the second semester, twenty lectures were provided over a three-dayperiod. The effects of these seminars were evaluated by Kirkpatrick's Learning Evaluation Model.
【Results】A total of 69 persons participated in these seminars, and their attendance was 99.1%. In regard to an opinion survey of participants after the program, 95.5% were satisfied with the presentation. The mean score of the writing test was 83.7±8.3, and that of participants in the first semester was higher than in the second semester. Many participants are now actively working as primary In-hp PTCs and establishing their own organ donation system in their respective hospitals.
【Conclusion】To refresh and update the knowledge and techniques required of In-hp PTCs, education programs of this kind should be established. For the present, in-hp PTCs working far from Osaka may prefer to attend the 3-day course.

We report the case of a kidney transplant recipient who was himself a nephrologist and first author of this report, and who found a sense of purpose in life despite his disease. At age 7, the patient was diagnosed with chronic kidney disease resulting from vesicoureteral reflux. After undergoing surgery, he had to maintain a strict diet along with medication to control disease progression. Two years after becoming a licensed nephrologist, he received a living donor kidney transplantation from his mother. He used his position as a nephrologist and a kidney transplant recipient to educate medical and nursing students on organ donations and transplantations and to promote deceased organ donations. However, despite his successes the patient suffered psychological issues throughout his life because of his disease. First, he experienced depression from learning the poor prognosis of chronic kidney disease patients. Second, he was bothered by fears of having to undergo dialysis therapy and dying. Third, he struggled with guilt after his successful kidney transplantation, knowing about the many dialysis patients who were forced to wait long periods for donor organs. Nevertheless, he was eventually able to accept his disease and discovered a sense of purpose in life by promoting deceased organ donations. Our observations suggest the importance of treating patients with chronic kidney disease not only physically, but also by caring for them psychologically.

A conclusion that immunosuppression and postoperative human immunodeficiency virus / hepatitis C (HIV/HCV) coinfected patient management for a liver transplantation has not been established. We performed 2 living donor and 1 deceased donor liver transplantations for patients with HIV/HCV coinfected end-stage liver disease. The immunosuppression protocol consisted of early calcineurin inhibitor-free and interleukin-2 receptor antagonist induction and methylprednisolone. Maintenance low-dose tacrolimus was started, and antiretroviral therapy for HIV was restarted 1 week after liver transplantation. Consecutively, anti-HCV therapy was added. Median 15 months later, HIV-RNA and HCV-RNA of all patients were undetectable on antiretroviral therapy and anti-HCV treatment with no drug-to-drug interactions. Interleukin-2 receptor antagonist induction with methylprednisolone immunosuppression in HIV/HCV coinfected patients was favorable.

The patient was a 60s-year-old man who had undergone a living-donor liver transplantation (LDLT) for alcoholic liver cirrhosis. The donor was his eldest son. One week before the scheduled date of liver transplantation, he complained about severe pain in the right pharynx. As a result of consultation to otolaryngology, a pharyngeal fiberscope showed a mucous membrane flare and an adhesion of the white patch to his right pharynx. We diagnosed him as herpes zoster pharyngitis, and aciclovir (750 mg/day, 7days) was administered against varicella zoster virus. We confirmed a cure of herpes zoster pharyngitis by an examination with pharyngeal fiberscope one week later. The patient underwent LDLT 10 days after confirmation of the pharyngitis cure. A posttransplant course was uneventful. The patient is currently doing well with good graft function.

Breast fibroadenoma (FA) is the most common breast tumor diagnosed in young women. Female patients treated with cyclosporine (CsA) show an increased risk of developing FA in renal transplants. However, the reports of FA in living-donor liver transplantations (LDLTs) are rare. Here we describe a case of de novo FA in a 16-year-old girl who had undergone an LDLT because of cirrhosis secondary to autoimmune hepatitis. She was maintained on a CsA-based immunosuppressive regimen. A breast ultrasound revealed a bilateral multiple breast mass, and the core needle biopsies of larger lesions were both FA. She underwent excision of the two symptomatic masses in her right breast, and the histopathological findings showed FA. Subsequently, CsA was replaced with tacrolimus. The fibroadenomas in her left breast decreased in size. CsA may increase the risk of FA in adolescent females after a liver transplantation.

Some reports have indicated that the blood concentration of most generic drugs is difficult to maintain stableility, and it may cause the difference in graft survival or nonsurvival of transplanted organs between original drugs and generic drugs. In this article, we report two cases that could not maintain blood concentration of generic drugs of mycophenolate mofetil (MMF).
Case 1: A nineteen-year-old patient. At the day of transplantation, MMF was changed to a generic drug. We found that the serum creatinine level was increased to 1.22 mg/dl at postoperative day 24. The plasma concentrations before the conversion of MMF was subthreshold. Therefore we changed the generic drug to the original drug. After that, the plasma concentration of MMF was increased to 2.4 μg/ml, and serum creatinine level was also improved to 0.96 mg/dl.
Case 2: An eight-year-old boy. He had continued diarrhea and was admitted to a hospital for general care. At that time, MMF was changed to a generic drug. The plasma concentrations of MMF were rapidly decreased to 0.6 μg/ml on the sixth day after admission. When the generic drug was changed to the original drug, it was increased again, to 3.7 μg/ml.
Conclusion: Some reports have indicated that a failure to maintain plasma concentration of MMF leads to rejection. Therefore maintenance of effective plasma concentration and prevention of rejection are essential to long-term graft survival in kidney transplants. In both cases, we discontinued use of the generic drugs thereafter because of unstable plasma concentrations of MMF.
Conversion to the generic drug may cause differences in effects and absorption. If the generic drug should be used patients should be closely monitored.