Living donor pancreas transplantation in Japan.

BACKGROUND/PURPOSE: Living-donor pancreas transplants (LDPs) were introduced at Chiba-East National Hospital in 2004, and 12 LDPs have been performed at this institution to date. Based on the outcome of these 12 LDPs, the efficacy and safety of LDPs are herein discussed. METHODS: Twelve diabetic patients underwent LDPs; ten had simultaneous pancreas and kidney transplants from living donors, one had pancreas transplant after a kidney transplant from a living donor, and one had a pancreas transplant alone from a living donor. The donors were parents or brothers and the ABO blood types were incompatible in three LDPs. The procedures for the donor and recipient operations were performed according to the technique established by the University of Minnesota. Bladder drainage was used in 11 recipients and enteric drainage was used in one patient. Tacrolimus, basiliximab, mycophenolate mofetil, and prednisone were used for induction and immunosuppressive treatment. A splenectomy, double-filtered plasmapheresis, and plasma exchange were added in the ABO-incompatible LDPs. RESULTS: No complications were observed in the donors during hospitalization. The 1-year survivals of the patients, kidney grafts, and pancreas grafts were 100, 100, and 100%, respectively. The 3-year survivals were 91.7, 90, and 91.7%, respectively. Three patients developed leakage of pancreatic juice and one patient required a surgical procedure. Cytomegalovirus antigenemia was detected in five patients (42%). CONCLUSIONS: Based on the excellent outcome of the LDPs at this institution, LDPs is therefore expected to become a promising option for the treatment of patients with severe diabetes.

Clinical islet transplantation in Japan.

INTRODUCTION: The results of clinical islet transplantation in Japan are, here in, reported and discussed its efficacy and problems. METHODS: Since the first islet transplantation was performed in 2004, 65 islet isolations and 34 islet transplantations to 18 type 1 diabetic patients have been performed in Japan. RESULTS: Following islet transplantation, patients experienced decreased insulin requirements and lower hemoglobin A1C levels, and positive serum C-peptide levels. All patients achieved stabilized blood glucose levels and the disappearance of hypoglycemic unawareness. Although three patients achieved insulin independency for a limited period, persistent islet graft function was difficult to maintain. Overall islet graft survival was 86.5% at 6 months, 78.7% at 1 year, and 62.9% at 2 years after the first islet transplantation. In our institution, we carried out 23 islet isolations and six islet transplantations to four patients. Although insulin independency was not achieved, all patients showed a disappearance of hypoglycemic unawareness. CONCLUSIONS: Using data from the Japanese Trial of Islet Transplantation, the effectiveness of islet transplantation was shown even when using the pancreata from non-heart-beating donors. Although there are a number of problems to be solved and further improvement is needed, we can state that the introduction of clinical islet transplantation offers hope for type 1 diabetic patients.

Cryopreservation of human pancreatic islets from non-heart-beating donors using hydroxyethyl starch and dimethyl sulfoxide as cryoprotectants.

Although widely used, DMSO is toxic for pancreatic islets. We combined hydroxyethyl starch (HES) with DMSO to simplify the procedure of freezing and thawing, and to decrease the toxicity of DMSO. A preclinical study was performed using islets from beagle dogs. After storage for 4 weeks, the islets were thawed and examined. The islet structure was well maintained after thawing. Although the number of the islets decreased to 71.2 +/- 20.1%, the function of the islets was evaluated by static incubation after thawing and showed a 1.80 +/- 0.78 stimulation index. We have introduced this technique for the cryopreservation of human islets from non-heart-beating donors. Twelve cases of human islet cryopreservation were performed. The sample tube of each human cryopreservation was thawed to evaluate the morphology, contamination, and endocrine function. Although fragmentation was observed in five samples (41.6%), the other seven (58.4%) showed a normal structure when evaluated by microscopic and electron microscopic study. The stimulation index (SI) of static incubation deteriorated from 3.37 +/- 3.02 to 1.34 +/- 0.28 after thawing. We divided the thawed islets into two groups: group 1 (n=8), SI > 1.2; group 2 (n=4), SI < 1.2. The group 1 islets showed a higher rate of normal structure (87%) than did group 2 (25%). Moreover, the SI before cryopreservation was 4.01 +/- 3.57 in group 1, which was higher than the SI of 2.11 +/- 0.72 in group 2. Based on the good results from the preclinical study using a large-animal model, this method was introduced for clinical application. Even from the pancreata of non-heart-beating donors, a successful islet cryopreservation was achieved. However, the isolated islets with poor function should not be cryopreserved for transplantation.

Acute cellular rejection occurring on the first day after living-related renal transplantation: a case report.

The patient was a 52-year-old man who received an ABO-compatible but non-identical living-related renal graft from his wife. The graft started to function immediately and the urine output rate was over 100 mL/h. However, this was gradually decreased within 12 h after transplantation. On day 2 post-transplant, the urine output almost stopped. A biopsy specimen revealed lymphocyte dominant cellular infiltration in the interstitium with mild tubulitis (according to Banff's schema grade Ia) and no C4d deposition in peritubular capillaries. Immunohistochemistry disclosed T-cell infiltration. The patient responded to a course of steroid pulse therapy (five days of 500 mg of methylprednisolone). The urine output gradually increased and the level of serum creatinine gradually decreased to 1.0 mg/dL. These clinical and histological findings strongly suggested acute cellular rejection. Acute cellular rejection occurring within 24 h post-transplant is extremely rare. In the present case acute cellular rejection occurred within the first day after living-related renal transplantation and was strongly suspected from histopathological findings in the allograft biopsy specimen.