An increasing number of lung transplant recipients in Japan are stepping into an unexplored posttransplant period. The upcoming issues they will face include such medical issues as chronic lung allograft dysfunction, adverse immunosuppressant effects and retransplantation requirement. Another problem will be social barriers to rehabilitation and fulltime regular employment that might undermine not only economic status but also the health condition of lung transplant recipients in the long term. This review overviews these important long-term issues after lung transplantation.

Since the heart transplantation (HTx) program was restarted in 1999, a total of 288 HTx procedures have been performed in Japan. The 10-year survival rate is 91.6%, which is excellent and better than International Society for Heart & Lung Transplantation (ISHLT) registry data (53%). This article reviewed Japanese registry data and ISHLT data to clarify the reason for excellent long-term outcomes in Japan and to discuss the future perspective of HTx in Japan.

The early outcomes of kidney transplantation in Japan have been improved with the development of immunosuppressive therapy. However, we have other problems such as chronic rejection, death with functioning graft (DWFG) and so on, that prevent long graft and patient survival. Some chronic rejection have immuno-reactive factors leading to graft loss, for which we have no established strategy. A novel immunosuppressant should be developed. Deaths of kidney transplant recipients have been caused by malignant disease, cardiovascular disease (CVD) and others. Preemptive kidney transplantations (PEKT) have been increased to avoid dialysis complications leading to CVD. For malignant disease, some strategies related with appropriate surveillance and necessary minimum immunosuppressive therapy should be established.

Liver transplantation is a treatment option for patients with end-stage liver diseases such as decompensated cirrhosis, acute liver failure, or metabolic liver diseases. From 1991 through 2014, a total of 4,922 adult living-donor liver transplantations and 227 adult deceased-donor liver transplantations (from heart-beating donors) were performed in Japan. Although short-term survival has been improved over time, improving long-term outcomes of long-term liver transplant survivors remains a challenge. They are at risk of morbidity and mortality associated with disease recurrence, systemic diseases, and de novo and recurrent malignancies or infections. The main point of this article is the long-term morbidity and mortality after liver transplantation.

Twenty-five years have passed since the liver transplantation program for children started in Japan. Numerous advances in pre- and posttransplant management and surgical techniques have improved the outcome. The Japanese Liver Transplantation Society have registered and followed all graft survivals since the 1989 start of the program. The results have been reported for 2224 cases up to December 2010. The current 20-year survival rate in children was at 79.6 %. Although short-term outcomes have become satisfactory, various issues faced by the long-term survivors have emerged. Here we described each complication associated with graft function, especially focusing on surgical and immunological factors.

The aim of the present study was to reveal the long-term outcomes of pancreas transplantation and to elucidate the risk factors that affect pancreatic graft survival in Japan.
We retrospectively analyzed a total of 246 cases of pancreas transplantation. After the exclusion of cases involving graft loss resulting from perioperative complications, the cases of 233 patients who underwent pancreas transplantation were divided into two groups: the simultaneous pancreas and kidney transplantation (SPK) group (n=188) and the pancreas transplantation after kidney and pancreas transplantation alone (PT) group (n=45) ; each group was analyzed to determine the factors associated with pancreatic graft survival.
The pancreatic graft survival rates at 1, 5, and 10 years after transplantation were 86.8%, 82.9%, and 74.9%, respectively, in the cases of SPK; and 85.1%, 42.2%, and 31.7%, respectively, in the cases of pancreas transplantation after kidney and pancreas transplantation alone, which amounted to a significant difference （P=4.81×10^‐5）. Episodes of rejection made pancreatic survival significantly lower in both groups. A multivariate analysis using Cox proportional hazards regression revealed that the preoperative period of diabetes （hazard ratio, 1.065; 95%CI, 1.009-1.125; P=0.02341） was significantly associated with pancreatic graft survival in the SPK group. HLA-A mismatch （hazard ratio, 2.153; 95%CI, 1.073-4.321; P= 0.03101） was the only factor associated with pancreatic graft survival in the PT group. Although the difference did not reach statistical significance, it was suggested that induction therapy with a T-cell depleting antibody would improve the rate of pancreatic graft survival in both groups.
In spite of the severe shortage of donors in Japan, simultaneous pancreas and kidney transplantation should be performed for type 1 diabetes patients with end-stage renal failure in the earlier stage, and HLA-A matching should be considered when selecting recipients to improve the rate of pancreatic graft survival in the PT group.

The treatment for hepatitis C virus (HCV) has dramatically changed with the introduction of direct-acting antivirals (DAAs). The efficacy and safety of interferon-free therapy before and after liver transplantation have been recently confirmed, beginning a new era in the strategy for treating HCV in transplant recipients. Establishment of treatment strategy for HCV in nonliver solid organ transplantation is currently in progress. Yet there are some minor unresolved issues, such as drug-drug interactions, treatment for decompensated cirrhosis, and treatment for renal failure. These problems are expected to be solved in the near future, and the poor prognosis of HCV-positive transplant recipients will improve.

【Objective】We investigated the efficacy and safety of conversion from twice-daily to once-daily tacrolimus formulation after heart transplantation.
【Design】Case-series study
【Methods】Ten heart transplant recipients who received twice-daily tacrolimus-based immunosuppressions were evaluated. The conversion to a once-daily tacrolimus formulation was undertaken at 822±290 days after transplantation. Four patients (40%) had the conversion during hospitalization for heart transplantation (Early conversion group). Six patients (60%) underwent conversion at our outpatient clinic (Late conversion group). The tacrolimus daily dose was adjusted to maintain target blood trough levels. Before conversion (baseline), immediately after conversion, 1 month after conversion, 3 months after conversion, and 6months after conversion, patients were evaluated clinically and by means of the usual blood chemistry and pharmacological parameters.
【Results】The mean age of ten patients was 36±15 years. The daily dose was changed from the mean value of 4.0±2.3 mg to 4.5±2.5 mg after conversion （p<0.05）. The administration of significantly increased daily doses was observed 1month or 6 months after conversion （p<0.05）. The trough level with blood sampling was stable throughout the conversion process. Renal function appeared to be impaired at 1 month after conversion, probably in response to the increased tacrolimus dose, but it ameliorated over the course of treatment by 6 months after conversion. Liver function, glucose intolerance, and serum lipid level were not affected by the conversion.
【Conclusion】Our data demonstrate that the conversion from twice-daily to once-daily tacrolimus formulation can be safely performed in patients having a heart transplantation. The daily dose of tacrolimus was increased to maintain target trough level. The necessity for such titration warrants further clinical studies.

【Objective】Complete surgical resection of a hepatoblastoma (HB) is required for long-term disease-free survival. For patients with unresectable HB, the only treatment option is total hepatectomy followed by liver transplantation (LTx). However the timing and indication of LTx and the protocol of post-transplant chemotherapy is not standardized. The aim of this study was to analyze the timing and outcome of LTx for unresectable HB.
【Design】Case series.
【Methods】We performed a retrospective study of seven children who received LTx for unresectable HB from 2005 to 2015.
【Results】All patients underwent living donor LTx. Their median age was 44 months （range, 27-199）. Four patients underwent primary LTx and three underwent rescue LTx. All patients received neoadjuvant chemotherapy, and the median number of the courses was 7 （range, 4-12）. The median interval from the last course of chemotherapy to LTx was 40 days （range, 21-118）. The median preparation period of living donors was 46 days （range, 21-110）. The median follow-up period was 24 months （range, 2-128）. All patients are alive and one relapsed after transplant.
【Conclusion】Previous reports encouraged that the decision of liver transplantation must be taken after no more than four courses of neoadjuvant therapy. Timely early referral of patients with potentially unresectable tumors to a center with expertise in liver tumor resection and LTx is required.

In Japan, living kidney donations are increasing instead of decreasing in relation to the number of cadaveric donors. Nowadays, most donors of nephrectomy have been handled through an endoscopic approach. The skill of endoscopic surgery is more crucial to ensure not only graft function, but also more donor safety than nephrectomy from other diseases, such as kidney cancer.
Our institute introduced endoscopic living donor nephrectomy in 2002. Ninety-one cases of hand-assisted laparoscopic living donor nephrectomy (HALDN) and more recently 292 cases of retroperitoneoscopic living donor nephrectomy (RPLDN) have been performed. At total of 10 endoscopic donor surgeons (EDS) are now established. The key to technical tradition of living donor nephrectomy is to shorten the learning curve to achieve unchanged graft outcomes and donor safety. Herein we compared the results of 4 experienced surgeons with those of 6 trainees concerning perioperative outcomes, complications, and learning curves to verify our EDS training program.

【Objective】There are two medical aspects regarding living donor liver transplantation (LDLT) for neonatal fulminant hepatic failure (FHF) : namely, neonatal and transplant medical care. We evaluated the specificity and issues of neonatal LDLT based on what we experienced at our institution.
【Methods】The study subjects included eight cases of neonatal FHF and 128 cases of other original diseases that underwent LDLT at our institution during the period from October 2008 to September 2015. Information on the family structure, social background, and psychological changes of family members during the perioperative period was retrospectively collected from the medical records, and the specificity and issues of neonatal LDLT were then analyzed.
【Results】The original diseases consisted of neonatal hemochromatosis in six patients, an unknown etiology in one, and Niemann-Pick type C in one. The median age of onset, age at LDLT, and current age were 0 days （0-19 days）, 32 days （9-59 days）, and 4.3 years old （1-7 years old）, respectively. The donors were the fathers in seven cases and the mothers in two, with the mothers being donors for cases in which the disease developed in siblings and in which the patient required retransplantation.
The median period of hospitalization was 98 days （40-631 days）, indicating a longer hospitalization period compared to patients with other original diseases. The neurological sequelae comprised visual impairment due to vitreous hemorrhage in one patient, hearing impairment due to an unknown etiology in one, and psychomotor retardation in one.
Three of the cases were first-born children; thus some problems were associated with parent training, and these parents required special assistance when the patients were discharged. On the other hand, in the non-first-born child cases there was less anxiety regarding parent training, and they required no special assistance at the time of discharge because of the parents' previous experience and family support system that was established while taking care of the patient's siblings.
【Conclusions】Regarding the families requiring neonatal LDLT, it is necessary for the transplant coordinator to carefully advise the family before LDLT and help them to establish their mental and social support system; specifically, if the patient is a first-born child, early intervention and support are essential.

We report a unique case of a 77-year-old woman with IgA nephropathy that occurred 6 years after she had donated a kidney to her son. Laboratory data of the patient before the donation showed an absence of urinary protein and sediment, and the serum creatinine level was 0.76 mg/dl. Four years after the donation, mild proteinuria and microscopic hematuria newly appeared. Five years after the donation, she developed hypertension and medication was initiated. Six years after the donation, swelling developed in both lower legs, the patient's creatinine levels elevated to 1.77 mg/dl, and the urinary protein level increased to 4.0 g/gCr. We performed an open kidney biopsy and diagnosed IgA nephropathy with crescent formation. Following steroid therapy, the patient's serum creatinine levels improved to 1.34 mg/dl and the urinary protein levels decreased to 0.6 g/gCr. The prompt diagnosis and treatment with steroid therapy prevented progression of kidney damage. It is necessary to perform regular follow-ups for urinalysis and kidney function after kidney donation to monitor kidney function.